Sample records for bind deleted domain

  1. Cellulose binding domain proteins

    DOE Patents [OSTI]

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

    1998-01-01T23:59:59.000Z

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

  2. Cellulose binding domain proteins

    DOE Patents [OSTI]

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

    1998-11-17T23:59:59.000Z

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

  3. Cellulose binding domain fusion proteins

    DOE Patents [OSTI]

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

    1998-02-17T23:59:59.000Z

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

  4. Cellulose binding domain fusion proteins

    DOE Patents [OSTI]

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

    1998-01-01T23:59:59.000Z

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

  5. Nucleic acids encoding a cellulose binding domain

    DOE Patents [OSTI]

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

    1996-01-01T23:59:59.000Z

    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.

  6. Nucleic acids encoding a cellulose binding domain

    DOE Patents [OSTI]

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

    1996-03-05T23:59:59.000Z

    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.

  7. Structural and Histone Binding Ability Characterizations of Human PWWP Domains

    SciTech Connect (OSTI)

    Wu, Hong; Zeng, Hong; Lam, Robert; Tempel, Wolfram; Amaya, Maria F.; Xu, Chao; Dombrovski, Ludmila; Qiu, Wei; Wang, Yanming; Min, Jinrong (Toronto); (Penn)

    2013-09-25T23:59:59.000Z

    The PWWP domain was first identified as a structural motif of 100-130 amino acids in the WHSC1 protein and predicted to be a protein-protein interaction domain. It belongs to the Tudor domain 'Royal Family', which consists of Tudor, chromodomain, MBT and PWWP domains. While Tudor, chromodomain and MBT domains have long been known to bind methylated histones, PWWP was shown to exhibit histone binding ability only until recently. The PWWP domain has been shown to be a DNA binding domain, but sequence analysis and previous structural studies show that the PWWP domain exhibits significant similarity to other 'Royal Family' members, implying that the PWWP domain has the potential to bind histones. In order to further explore the function of the PWWP domain, we used the protein family approach to determine the crystal structures of the PWWP domains from seven different human proteins. Our fluorescence polarization binding studies show that PWWP domains have weak histone binding ability, which is also confirmed by our NMR titration experiments. Furthermore, we determined the crystal structures of the BRPF1 PWWP domain in complex with H3K36me3, and HDGF2 PWWP domain in complex with H3K79me3 and H4K20me3. PWWP proteins constitute a new family of methyl lysine histone binders. The PWWP domain consists of three motifs: a canonical {beta}-barrel core, an insertion motif between the second and third {beta}-strands and a C-terminal {alpha}-helix bundle. Both the canonical {beta}-barrel core and the insertion motif are directly involved in histone binding. The PWWP domain has been previously shown to be a DNA binding domain. Therefore, the PWWP domain exhibits dual functions: binding both DNA and methyllysine histones.

  8. A Double-Deletion Method to Quantifying Incremental Binding Energies in Proteins from Experiment: Example of a Destabilizing Hydrogen

    E-Print Network [OSTI]

    Sancho, Javier

    A Double-Deletion Method to Quantifying Incremental Binding Energies in Proteins from Experiment: Example of a Destabilizing Hydrogen Bonding Pair Luis A. Campos,*y Santiago Cuesta-Lo´pez,*z Jon Lo of a specific hydrogen bond in apoflavodoxin to protein stability is investigated by combining theory

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

    DOE Patents [OSTI]

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

    1999-01-01T23:59:59.000Z

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

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

    DOE Patents [OSTI]

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

    1999-01-05T23:59:59.000Z

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

  11. Methods of use of cellulose binding domain proteins

    DOE Patents [OSTI]

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

    1997-01-01T23:59:59.000Z

    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.

  12. Methods of use of cellulose binding domain proteins

    DOE Patents [OSTI]

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

    1997-09-23T23:59:59.000Z

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

  13. Molecular dissection of the roles of nucleotide binding and hydrolysis in dynein's AAA domains

    E-Print Network [OSTI]

    Vale, Ronald D.

    Molecular dissection of the roles of nucleotide binding and hydrolysis in dynein's AAA domains (ATPase associated with various cellular activities) domains that are thought to bind nucleotide; the role of nucleotide binding and hydrolysis in each of these four AAA domains has constituted an important and unre

  14. Solution Structure of the cGMP Binding GAF Domain fromPhosphodiesteras...

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

    of cGMP through its regulation of cGMP hydrolysis. Hydrolytic activity of the C-terminal catalytic domain is increased by cGMP binding to the N-terminal GAF A domain. We...

  15. CCAAT/enhancer binding protein {beta} deletion increases mitochondrial function and protects mice from LXR-induced hepatic steatosis

    SciTech Connect (OSTI)

    Rahman, Shaikh M., E-mail: rmizanoor@hotmail.com [Department of Pediatrics, School of Medicine, University of Colorado Denver, Aurora, CO 80045 (United States); Choudhury, Mahua; Janssen, Rachel C.; Baquero, Karalee C. [Department of Pediatrics, School of Medicine, University of Colorado Denver, Aurora, CO 80045 (United States)] [Department of Pediatrics, School of Medicine, University of Colorado Denver, Aurora, CO 80045 (United States); Miyazaki, Makoto [Division of Renal Diseases and Hypertension, School of Medicine, University of Colorado Denver, Aurora, CO 80045 (United States)] [Division of Renal Diseases and Hypertension, School of Medicine, University of Colorado Denver, Aurora, CO 80045 (United States); Friedman, Jacob E. [Department of Pediatrics, School of Medicine, University of Colorado Denver, Aurora, CO 80045 (United States) [Department of Pediatrics, School of Medicine, University of Colorado Denver, Aurora, CO 80045 (United States); Department of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado Denver, Aurora, CO 80045 (United States)

    2013-01-04T23:59:59.000Z

    Highlights: Black-Right-Pointing-Pointer LXR agonist activation increases liver TG accumulation by increasing lipogenesis. Black-Right-Pointing-Pointer C/EBP{beta}{sup -/-} mouse prevents LXR activation-mediated induction of hepatic lipogenesis. Black-Right-Pointing-Pointer C/EBP{beta} deletion increases mitochondrial transport chain function. Black-Right-Pointing-Pointer Beneficial effects of LXR activation on liver cholesterol metabolism did not change. Black-Right-Pointing-Pointer C/EBP{beta} inhibition might have important therapeutic potential. -- Abstract: Drugs designed specifically to activate liver X receptors (LXRs) have beneficial effects on lowering cholesterol metabolism and inflammation but unfortunately lead to severe hepatic steatosis. The transcription factor CCAAT/enhancer binding protein beta (C/EBP{beta}) is an important regulator of liver gene expression but little is known about its involvement in LXR-based steatosis and cholesterol metabolism. The present study investigated the role of C/EBP{beta} expression in LXR agonist (T0901317)-mediated alteration of hepatic triglyceride (TG) and lipogenesis in mice. C/EBP{beta} deletion in mice prevented LXR agonist-mediated induction of lipogenic gene expression in liver in conjunction with significant reduction of liver TG accumulation. Surprisingly, C/EBP{beta}{sup -/-} mice showed a major increase in liver mitochondrial electron chain function compared to WT mice. Furthermore, LXR activation in C/EBP{beta}{sup -/-} mice increased the expression of liver ATP-binding cassette transporter ABCG1, a gene implicated in cholesterol efflux and reducing blood levels of total and LDL-cholesterol. Together, these findings establish a central role for C/EBP{beta} in the LXR-mediated steatosis and mitochondrial function, without impairing the influence of LXR activation on lowering LDL and increasing HDL-cholesterol. Inactivation of C/EBP{beta} might therefore be an important therapeutic strategy to prevent LXR activation-mediated adverse effects on liver TG metabolism without disrupting its beneficial effects on cholesterol metabolism.

  16. A Novel Dimerization Interface of Cyclic Nucleotide Binding Domain, which is

    E-Print Network [OSTI]

    Paris-Sud XI, Université de

    1 A Novel Dimerization Interface of Cyclic Nucleotide Binding Domain, which is Disrupted Modeling 18, 9 (2012) 4053-4060" DOI : 10.1007/s00894-012-1404-5 #12;2 ABSTRACT Cyclic nucleotide binding and eukaryota. CNBD activation by cyclic nucleotide monophosphate (cNMP) is studied well in case of several

  17. The N-terminal domain determines the affinity and specificity of H1 binding to chromatin

    SciTech Connect (OSTI)

    Oeberg, Christine, E-mail: christine.oberg@ki.se [Karolinska Institute, Department of Cell and Molecular Biology, P.O. Box 285, SE-17177 Stockholm (Sweden)] [Karolinska Institute, Department of Cell and Molecular Biology, P.O. Box 285, SE-17177 Stockholm (Sweden); Belikov, Sergey, E-mail: sergey.belikov@ki.se [Karolinska Institute, Department of Cell and Molecular Biology, P.O. Box 285, SE-17177 Stockholm (Sweden)] [Karolinska Institute, Department of Cell and Molecular Biology, P.O. Box 285, SE-17177 Stockholm (Sweden)

    2012-04-06T23:59:59.000Z

    Highlights: Black-Right-Pointing-Pointer wt Human histone H1.4 and hH1.4 devoid of N-terminal domain, {Delta}N-hH1.4, were compared. Black-Right-Pointing-Pointer Both histones bind to chromatin, however, {Delta}N-hH1.4 displays lower binding affinity. Black-Right-Pointing-Pointer Interaction of {Delta}N-hH1.4 with chromatin includes a significant unspecific component. Black-Right-Pointing-Pointer N-terminal domain is a determinant of specificity of histone H1 binding to chromatin. -- Abstract: Linker histone H1, one of the most abundant nuclear proteins in multicellular eukaryotes, is a key component of the chromatin structure mainly due to its role in the formation and maintenance of the 30 nm chromatin fiber. It has a three-domain structure; a central globular domain flanked by a short N-terminal domain and a long, highly basic C-terminal domain. Previous studies have shown that the binding abilities of H1 are at large determined by the properties of the C-terminal domain; much less attention has been paid to role of the N-terminal domain. We have previously shown that H1 can be reconstituted via cytoplasmic mRNA injection in Xenopus oocytes, cells that lack somatic H1. The heterologously expressed H1 proteins are incorporated into in vivo assembled chromatin at specific sites and the binding event is monitored as an increase in nucleosomal repeat length (NRL). Using this setup we have here compared the binding properties of wt-H1.4 and hH1.4 devoid of its N-terminal domain ({Delta}N-hH1.4). The {Delta}N-hH1.4 displays a drastically lower affinity for chromatin binding as compared to the wild type hH1.4. Our data also indicates that {Delta}N-hH1.4 is more prone to unspecific chromatin binding than the wild type. We conclude that the N-terminal domain of H1 is an important determinant of affinity and specificity of H1-chromatin interactions.

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

    DOE Patents [OSTI]

    Shoseyov, O.; Yosef, K.

    1998-04-14T23:59:59.000Z

    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.

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

    DOE Patents [OSTI]

    Shoseyov, Oded (Karmey Yosef, IL)

    1998-01-01T23:59:59.000Z

    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.

  20. A new protein folding screen: Application to the ligand binding domains of a glutamate and kainate

    E-Print Network [OSTI]

    Lebendiker, Mario

    A new protein folding screen: Application to the ligand binding domains of a glutamate and kainate of determining and evaluating protein folding conditions, we have designed a new fractional factorial protein folding screen. The screen includes 12 factors shown by previous experiments to enhance protein folding

  1. Analysis of the hormone-binding domain of steroid receptors using chimeras generated by homologous recombination

    SciTech Connect (OSTI)

    Martinez, Elisabeth D. [Department of Biochemistry and Molecular Biology, Georgetown University School of Medicine, Washington, DC 20057 (United States); Pattabiraman, Nagarajan [Department of Biochemistry and Molecular Biology, Georgetown University School of Medicine, Washington, DC 20057 (United States); Department of Oncology, Georgetown University School of Medicine, Washington, DC 20057 (United States); Danielsen, Mark [Department of Biochemistry and Molecular Biology, Georgetown University School of Medicine, Washington, DC 20057 (United States)]. E-mail: dan@bc.georgetown.edu

    2005-08-15T23:59:59.000Z

    The glucocorticoid receptor and the mineralocorticoid receptor are members of the steroid receptor family that exhibit ligand cross-reactivity. Specificity of steroid receptor action is investigated in the present work by the construction and characterization of chimeras between the glucocorticoid receptor and the mineralocorticoid receptor. We used an innovative approach to make novel steroid receptor proteins in vivo that in general, contrary to our expectations, show increased ligand specificity compared to the parental receptors. We describe a receptor that is specific for the potent synthetic glucocorticoid triamcinolone acetonide and does not bind aldosterone. A further set of chimeras has an increased ability to discriminate between ligands, responding potently to mineralocorticoids and only very weakly to synthetic glucocorticoids. A chimera with the fusion site in the hinge highlights the importance of the region between the DNA-binding and the hormone-binding domains since, unlike both the glucocorticoid and mineralocorticoid receptors, it only responds to mineralocorticoids. One chimera has reduced specificity in that it acts as a general corticoid receptor, responding to glucocorticoids and mineralocorticoids with similar potency and efficacy. Our data suggest that regions of the glucocorticoid and mineralocorticoid receptor hormone-binding domains are functionally non-reciprocal. We present transcriptional, hormone-binding, and structure-modeling evidence that suggests that receptor-specific interactions within and across domains mediate aspects of specificity in transcriptional responses to steroids.

  2. Stabilizing the cystic fibrosis transmembrane conductance regulator (CFTR) by nucleotide derivative binding to promote proper folding

    E-Print Network [OSTI]

    Smith, Ryan Craig

    2013-02-22T23:59:59.000Z

    Seventy percent of people who suffer from cystic fibrosis have a cystic fibrosis transmembrane conductance regulator gene on chromosome 7 that contains a three base-pair deletion of phenylalanine at position 508, in a nucleotide binding domain...

  3. Mechanism of Ubiquinol Oxidation by the bc1 Complex: Different Domains of the Quinol Binding Pocket and Their Role in the Mechanism and Binding of Inhibitors

    E-Print Network [OSTI]

    Crofts, Antony R.

    electron-transfer systems, occurring ubiquitously in respiratory and photosynthetic chains of mitochondriaMechanism of Ubiquinol Oxidation by the bc1 Complex: Different Domains of the Quinol Binding Pocket and Their Role in the Mechanism and Binding of Inhibitors Antony R. Crofts,*, Blanca Barquera, Robert B. Gennis

  4. Mutational analysis of the RNA-binding domain of the Prunus necrotic ringspot virus (PNRSV) movement protein reveals its requirement for cell-to-cell movement

    SciTech Connect (OSTI)

    Carmen Herranz, Ma [Instituto de Biologia Molecular y Celular de Plantas (IBMCP), UPV-CSIC, Avda. de los Naranjos, s/n, 46022, Valencia (Spain); Sanchez-Navarro, Jesus-Angel [Instituto de Biologia Molecular y Celular de Plantas (IBMCP), UPV-CSIC, Avda. de los Naranjos, s/n, 46022, Valencia (Spain); Sauri, Ana [Departament de Bioquimica i Biologia Molecular, Universitat de Valencia, E-46100 Burjassot (Spain); Mingarro, Ismael [Departament de Bioquimica i Biologia Molecular, Universitat de Valencia, E-46100 Burjassot (Spain); Pallas, Vicente [Instituto de Biologia Molecular y Celular de Plantas (IBMCP), UPV-CSIC, Avda. de los Naranjos, s/n, 46022, Valencia (Spain)]. E-mail: vpallas@ibmcp.upv.es

    2005-08-15T23:59:59.000Z

    The movement protein (MP) of Prunus necrotic ringspot virus (PNRSV) is required for cell-to-cell movement. MP subcellular localization studies using a GFP fusion protein revealed highly punctate structures between neighboring cells, believed to represent plasmodesmata. Deletion of the RNA-binding domain (RBD) of PNRSV MP abolishes the cell-to-cell movement. A mutational analysis on this RBD was performed in order to identify in vivo the features that govern viral transport. Loss of positive charges prevented the cell-to-cell movement even though all mutants showed a similar accumulation level in protoplasts to those observed with the wild-type (wt) MP. Synthetic peptides representing the mutants and wild-type RBDs were used to study RNA-binding affinities by EMSA assays being approximately 20-fold lower in the mutants. Circular dichroism analyses revealed that the secondary structure of the peptides was not significantly affected by mutations. The involvement of the affinity changes between the viral RNA and the MP in the viral cell-to-cell movement is discussed.

  5. Structure and interactions of the C-terminal metal binding domain of Archaeoglobus fulgidus CopA

    SciTech Connect (OSTI)

    Agarwal, S.; Hong, D.; Desai, N.K.; H.Sazinsky, M.; Argello, J.M.; Rosenzweig, A.C. (NWU)

    2010-08-13T23:59:59.000Z

    The Cu(+)-ATPase CopA from Archaeoglobus fulgidus belongs to the P(1B) family of the P-type ATPases. These integral membrane proteins couple the energy of ATP hydrolysis to heavy metal ion translocation across membranes. A defining feature of P(1B-1)-type ATPases is the presence of soluble metal binding domains at the N-terminus (N-MBDs). The N-MBDs exhibit a conserved ferredoxin-like fold, similar to that of soluble copper chaperones, and bind metal ions via a conserved CXXC motif. The N-MBDs enable Cu(+) regulation of turnover rates apparently through Cu-sensitive interactions with catalytic domains. A. fulgidus CopA is unusual in that it contains both an N-terminal MBD and a C-terminal MBD (C-MBD). The functional role of the unique C-MBD has not been established. Here, we report the crystal structure of the apo, oxidized C-MBD to 2.0 A resolution. In the structure, two C-MBD monomers form a domain-swapped dimer, which has not been observed previously for similar domains. In addition, the interaction of the C-MBD with the other cytoplasmic domains of CopA, the ATP binding domain (ATPBD) and actuator domain (A-domain), has been investigated. Interestingly, the C-MBD interacts specifically with both of these domains, independent of the presence of Cu(+) or nucleotides. These data reinforce the uniqueness of the C-MBD and suggest a distinct structural role for the C-MBD in CopA transport.

  6. NMR Structures of Salt-Refolded Forms of the 434-Repressor DNA-Binding Domain in 6 M Urea

    E-Print Network [OSTI]

    Wider, Gerhard

    NMR Structures of Salt-Refolded Forms of the 434-Repressor DNA-Binding Domain in 6 M Urea- 8). Examples are salt-induced refolding of proteins at acidic pH (9), leading to the formation), and lysozyme (14) allowed detailed structural and dynamic characterization of salt-stabilized A-states, which

  7. Evaluation of selected binding domains for the analysis of ubiquitinated proteomes

    SciTech Connect (OSTI)

    Nakayasu, Ernesto S.; Ansong, Charles; Brown, Joseph N.; Yang, Feng; Lopez-Ferrer, Dani; Qian, Weijun; Smith, Richard D.; Adkins, Joshua N.

    2013-08-07T23:59:59.000Z

    Ubiquitination is an abundant post-translational modification that consists of covalent attachment of a 76 amino acid residue polypeptide, ubiquitin, to lysine residues or the N-terminus of proteins. Mono and polyubiquitination have been shown to be involved in many critical eukaryotic cellular functions. Affinity enrichment of ubiquitinated proteins has enabled the global analysis of this key modification. In this context, the use of ubiquitin-binding domains (UBDs) is a promising, but poorly explored alternative to more broadly used immune-affinity or tagged affinity enrichment methods. Herein we evaluate the application of eight selected UBDs with differing and contrasting affinities for ubiquitination states. We performed a micro-scale proteomic comparison, leading to the identification of ~200 ubiquitinated protein candidates per UBD to facilitate comparisons. Western blot analysis using anti-ubiquitin or monoclonal antibodies against polyubiquitination at lysine 48 and 63 suggests that UBDs from Dsk2 and ubiquilin-1 have the broadest specificity capturing most types of ubiquitination, whereas the one from NBR1 seems to be more selective to polyubiquitination. Our data demonstrate that with optimized purification conditions UBDs can be a useful tool for proteomic applications.

  8. Crystal structure of the Candida albicans Kar3 kinesin motor domain fused to maltose-binding protein

    SciTech Connect (OSTI)

    Delorme, Caroline; Joshi, Monika [Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada K7L 3N6 (Canada)] [Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada K7L 3N6 (Canada); Allingham, John S., E-mail: allinghj@queensu.ca [Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada K7L 3N6 (Canada)

    2012-11-30T23:59:59.000Z

    Highlights: Black-Right-Pointing-Pointer The Candida albicans Kar3 motor domain structure was solved as a maltose-binding protein fusion. Black-Right-Pointing-Pointer The electrostatic surface and part of the ATPase pocket of the motor domain differs markedly from other kinesins. Black-Right-Pointing-Pointer The MBP-Kar3 interface highlights a new site for intramolecular or intermolecular interactions. -- Abstract: In the human fungal pathogen Candida albicans, the Kinesin-14 motor protein Kar3 (CaKar3) is critical for normal mitotic division, nuclear fusion during mating, and morphogenic transition from the commensal yeast form to the virulent hyphal form. As a first step towards detailed characterization of this motor of potential medical significance, we have crystallized and determined the X-ray structure of the motor domain of CaKar3 as a maltose-binding protein (MBP) fusion. The structure shows strong conservation of overall motor domain topology to other Kar3 kinesins, but with some prominent differences in one of the motifs that compose the nucleotide-binding pocket and the surface charge distribution. The MBP and Kar3 modules are arranged such that MBP interacts with the Kar3 motor domain core at the same site where the neck linker of conventional kinesins docks during the 'ATP state' of the mechanochemical cycle. This site differs from the Kar3 neck-core interface in the recent structure of the ScKar3Vik1 heterodimer. The position of MBP is also completely distinct from the Vik1 subunit in this complex. This may suggest that the site of MBP interaction on the CaKar3 motor domain provides an interface for the neck, or perhaps a partner subunit, at an intermediate state of its motile cycle that has not yet been observed for Kinesin-14 motors.

  9. Structural Insights into the Functional Role of the Hcn Sub-domain of the Receptor-Binding Domain of the Botulinum Neurotoxin Mosaic Serotype C/D

    SciTech Connect (OSTI)

    Zhang, Yanfeng; Gardberg, Anna; Edwards, Tom E.; Sankaran, Banumathi; Robinson, Howard; Varnum, Susan M.; Buchko, Garry W.

    2013-07-01T23:59:59.000Z

    Botulinum neurotoxin (BoNT), the causative agent of the deadly neuroparalytic disease botulism, is the most poisonous protein known for humans. Produced by different strains of the anaerobic bacterium Clostridium botulinum, BoNT effects cellular intoxication via a multistep mechanism executed by the three modules of the activated protein. Endocytosis, the first step of cellular intoxication, is triggered by the ~50 kDa, heavy-chain receptor-binding module (HCR) that is specific for a ganglioside and a protein receptor on neuronal cell surfaces. This dual receptor recognition mechanism between BoNT and the host cells membrane is well documented and occurs via specific intermolecular interactions with the C-terminal sub-domain, Hcc, of BoNT-HCR. The N-terminal sub-domain of BoNT-HCR, Hcn, comprises ~50% of BoNT-HCR and adopts a B-sheet jelly roll fold. While suspected in assisting cell surface recognition, no unambiguous function for the Hcn sub-domain in BoNT has been indentified. To obtain insights into the potential function of the Hcn sub-domain in BoNT, the first crystal structure of a BoNT with an organic ligand bound to the Hcn sub-domain has been obtained. Here, we describe the crystal structure of BoNT/CD-HCR determined at 1.70 resolution with a tetraethylene glycol (PG4) molecule bound in an hydrophobic cleft between B-strands in the B-sheet jelly fold roll of the Hcn sub-domain. The molecule is completely engulfed in the cleft, making numerous hydrophobic (Y932, S959, W966, and D1042) and hydrophilic (S935, W977, L979, N1013, and I1066) contacts with the proteins side chain and backbone that may mimic in vivo interactions with the phospholipid membranes on neuronal cell surfaces. A sulfate ion was also observed bound to residues T1176, D1177, K1196, and R1243 in the Hcc sub-domain of BoNT/CD-HCR. In the crystal structure of a similar protein, BoNT/D-HCR, a sialic acid

  10. Biochemistry 1992, 31, 3463-347 1 3463 Three-Dimensional Solution Structure of the E3-Binding Domain of the

    E-Print Network [OSTI]

    Clore, G. Marius

    2-oxoglutarate dehydrogenase (2-OGDH), pyruvate dehydrogenase (PDH), and branched-chain 2-oxo acid-39). This report presents the first structure of an E3-binding domain from a 2-oxo acid dehydrogenasecomplex. Related domains from the E2 chains of other 2-oxo acid dehydrogenase complexes are likely

  11. 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. (Toledo); (Vanderbilt)

    2014-10-02T23:59:59.000Z

    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.

  12. 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.; (UTSMC)

    2010-09-21T23:59:59.000Z

    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.

  13. Comparison of the Structures and Peptide Binding Specificities of the BRCT Domains

    E-Print Network [OSTI]

    Glover, Mark

    Domains of MDC1 and BRCA1 Stephen J. Campbell,1 Ross A. Edwards,1 and J.N. Mark Glover1,* 1Department of Biochemistry, University of Alberta, Edmonton, AB T6G 2H7, Canada *Correspondence: mark.glover@ualberta.ca DOI (Clapperton et al., 2004; Glover et al., 2004; Shiozaki et al., 2004; Williams et al., 2004) (Figure 1B

  14. A Single-Domain Llama Antibody Potently Inhibits the Enzymatic Activity of Botulinum Neurotoxin by Binding to the Non-Catalytic [alpha]-Exosite Binding Region

    SciTech Connect (OSTI)

    Dong, Jianbo; Thompson, Aaron A.; Fan, Yongfeng; Lou, Jianlong; Conrad, Fraser; Ho, Mengfei; Pires-Alves, Melissa; Wilson, Brenda A.; Stevens, Raymond C.; Marks, James D. (UIUC); (Scripps); (UCSF)

    2010-08-13T23:59:59.000Z

    Ingestion or inhalation of botulinum neurotoxin (BoNT) results in botulism, a severe and frequently fatal disease. Current treatments rely on antitoxins, which, while effective, cannot reverse symptoms once BoNT has entered the neuron. For treatments that can reverse intoxication, interest has focused on developing inhibitors of the enzymatic BoNT light chain (BoNT Lc). Such inhibitors typically mimic substrate and bind in or around the substrate cleavage pocket. To explore the full range of binding sites for serotype A light chain (BoNT/A Lc) inhibitors, we created a library of non-immune llama single-domain VHH (camelid heavy-chain variable region derived from heavy-chain-only antibody) antibodies displayed on the surface of the yeast Saccharomyces cerevisiae. Library selection on BoNT/A Lc yielded 15 yeast-displayed VHH with equilibrium dissociation constants (K{sub d}) from 230 to 0.03 nM measured by flow cytometry. Eight of 15 VHH inhibited the cleavage of substrate SNAP25 (synaptosome-associated protein of 25,000 Da) by BoNT/A Lc. The most potent VHH (Aa1) had a solution K{sub d} for BoNT/A Lc of 1.47 x 10{sup -10} M and an IC{sub 50} (50% inhibitory concentration) of 4.7 x 10{sup -10} M and was resistant to heat denaturation and reducing conditions. To understand the mechanism by which Aa1 inhibited catalysis, we solved the X-ray crystal structure of the BoNT/A Lc-Aa1 VHH complex at 2.6 {angstrom} resolution. The structure reveals that the Aa1 VHH binds in the {alpha}-exosite of the BoNT/A Lc, far from the active site for catalysis. The study validates the utility of non-immune llama VHH libraries as a source of enzyme inhibitors and identifies the BoNT/A Lc {alpha}-exosite as a target for inhibitor development.

  15. Identification of High Affinity Polo-like Kinase 1 (Plk1) Polo-box Domain Binding Peptides Using Oxime-Based Diversification

    E-Print Network [OSTI]

    Liu, Fa

    In an effort to develop improved binding antagonists of the polo-like kinase 1 (Plk1) polo-box domain (PBD), we optimized interactions of the known high affinity 5-mer peptide PLHSpT using oxime-based post solid-phase ...

  16. Improving the fidelity of deletion

    SciTech Connect (OSTI)

    Adhikari, Satyabrata; Choudhury, B. S. [Department of Mathematics, Bengal Engineering and Science University, Howrah-711103, West Bengal (India)

    2006-05-15T23:59:59.000Z

    In this work we study the quantum deletion machine with two transformers, and show that the deletion machine with a single transformer performs better than the deletion machine with more than two transformers. We also observe that the fidelity of deletion depends on the blank state used in the deleter, and so for different blank states the fidelity is different. Further, we study the Pati-Braunsein deleter with transformer.

  17. Structures of the HIN Domain:DNA Complexes Reveal Ligand Binding and Activation Mechanisms of the AIM2 Inflammasome and IFI16 Receptor

    SciTech Connect (OSTI)

    Jin, Tengchuan; Perry, Andrew; Jiang, Jiansheng; Smith, Patrick; Curry, James A.; Unterholzner, Leonie; Jiang, Zhaozhao; Horvath, Gabor; Rathinam, Vijay A.; Johnstone, Ricky W.; Hornung, Veit; Latz, Eicke; Bowie, Andrew G.; Fitzgerald, Katherine A.; Xiao, T. Sam (UMASS, MED); (Bonn); (Trinity); (PMCI-A); (NIH)

    2012-05-21T23:59:59.000Z

    Recognition of DNA by the innate immune system is central to antiviral and antibacterial defenses, as well as an important contributor to autoimmune diseases involving self DNA. AIM2 (absent in melanoma 2) and IFI16 (interferon-inducible protein 16) have been identified as DNA receptors that induce inflammasome formation and interferon production, respectively. Here we present the crystal structures of their HIN domains in complex with double-stranded (ds) DNA. Non-sequence-specific DNA recognition is accomplished through electrostatic attraction between the positively charged HIN domain residues and the dsDNA sugar-phosphate backbone. An intramolecular complex of the AIM2 Pyrin and HIN domains in an autoinhibited state is liberated by DNA binding, which may facilitate the assembly of inflammasomes along the DNA staircase. These findings provide mechanistic insights into dsDNA as the activation trigger and oligomerization platform for the assembly of large innate signaling complexes such as the inflammasomes.

  18. 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.

    2010-03-11T23:59:59.000Z

    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.

  19. 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)

    2008-07-29T23:59:59.000Z

    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.

  20. Crystallographic Analysis of Murine Constitutive Androstane Receptor Ligand-Binding Domain Complexed with 5[alpha]-androst-16-en-3[alpha]-ol

    SciTech Connect (OSTI)

    Vincent, J.; Shan, L.; Fan, M.; Brunzelle, J.S.; Forman, B.M.; Fernandez, E.J. (Tennessee-K); (NWU); (CHNMC)

    2010-03-08T23:59:59.000Z

    The constitutive androstane receptor (CAR) is a member of the nuclear receptor superfamily. In contrast to classical nuclear receptors, which possess small-molecule ligand-inducible activity, CAR exhibits constitutive transcriptional activity in the apparent absence of ligand. CAR is among the most important transcription factors; it coordinately regulates the expression of microsomal cytochrome P450 genes and other drug-metabolizing enzymes. The murine CAR ligand-binding domain (LBD) was coexpressed with the steroid receptor coactivator protein (SRC-1) receptor-interacting domain (RID) in Escherichia coli. The mCAR LBD subunit was purified away from SRC-1 by affinity, anion-exchange and size-exclusion chromatography, crystallized with androstenol and the structure of the complex determined by molecular replacement.

  1. The E3 Ubiquitin Ligase- and Protein Phosphatase 2A (PP2A)-binding Domains of the Alpha4 Protein Are Both Required for Alpha4 to Inhibit PP2A Degradation

    SciTech Connect (OSTI)

    LeNoue-Newton, Michele; Watkins, Guy R.; Zou, Ping; Germane, Katherine L.; McCorvey, Lisa R.; Wadzinski, Brian E.; Spiller, Benjamin W. (Vanderbilt)

    2012-04-30T23:59:59.000Z

    Protein phosphatase 2A (PP2A) is regulated through a variety of mechanisms, including post-translational modifications and association with regulatory proteins. Alpha4 is one such regulatory protein that binds the PP2A catalytic subunit (PP2Ac) and protects it from polyubiquitination and degradation. Alpha4 is a multidomain protein with a C-terminal domain that binds Mid1, a putative E3 ubiquitin ligase, and an N-terminal domain containing the PP2Ac-binding site. In this work, we present the structure of the N-terminal domain of mammalian Alpha4 determined by x-ray crystallography and use double electron-electron resonance spectroscopy to show that it is a flexible tetratricopeptide repeat-like protein. Structurally, Alpha4 differs from its yeast homolog, Tap42, in two important ways: (1) the position of the helix containing the PP2Ac-binding residues is in a more open conformation, showing flexibility in this region; and (2) Alpha4 contains a ubiquitin-interacting motif. The effects of wild-type and mutant Alpha4 on PP2Ac ubiquitination and stability were examined in mammalian cells by performing tandem ubiquitin-binding entity precipitations and cycloheximide chase experiments. Our results reveal that both the C-terminal Mid1-binding domain and the PP2Ac-binding determinants are required for Alpha4-mediated protection of PP2Ac from polyubiquitination and degradation.

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

    SciTech Connect (OSTI)

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

    2014-05-01T23:59:59.000Z

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

  3. The BARD1 C-Terminal Domain Structure and Interactions with Polyadenylation Factor CstF-50

    SciTech Connect (OSTI)

    Edwards, Ross A.; Lee, Megan S.; Tsutakawa, Susan E.; Williams, R. Scott; Tainer, John A.; Glover, J. N. Mark

    2009-07-13T23:59:59.000Z

    The BARD1 N-terminal RING domain binds BRCA1 while the BARD1 C-terminal ankyrin and tandem BRCT repeat domains bind CstF-50 to modulate mRNA processing and RNAP II stability in response to DNA damage. Here we characterize the BARD1 structural biochemistry responsible for CstF- 50 binding. The crystal structure of the BARD1 BRCT domain uncovers a degenerate phosphopeptide binding pocket lacking the key arginine required for phosphopeptide interactions in other BRCT proteins.Small angle X-ray scattering together with limited proteolysis results indicates that ankyrin and BRCT domains are linked by a flexible tether and do not adopt a fixed orientation relative to one another. Protein pull-down experiments utilizing a series of purified BARD1 deletion mutants indicate that interactions between the CstF-50 WD-40 domain and BARD1 involve the ankyrin-BRCT linker but do not require ankyrin or BRCT domains. The structural plasticity imparted by the ANK-BRCT linker helps to explain the regulated assembly of different protein BARD1 complexes with distinct functions in DNA damage signaling including BARD1-dependent induction of apoptosis plus p53 stabilization and interactions. BARD1 architecture and plasticity imparted by the ANK-BRCT linker are suitable to allow the BARD1 C-terminus to act as a hub with multiple binding sites to integrate diverse DNA damage signals directly to RNA polymerase.

  4. GTPase Activating Specificity of RGS12 and Binding Specificity of an Alternatively Spliced PDZ (PSD-95/Dlg/ZO-1) Domain*

    E-Print Network [OSTI]

    Hall, Randy A

    spliced PDZ domain within RGS12 suggests a mechanism by which RGS proteins may tar- get specific G amino acid motifs at the extreme carboxyl termini of target proteins (reviewed in Ref. 11). PDZ domains

  5. Identification of new functions for BRCT domains

    E-Print Network [OSTI]

    Mohammad, Duaa H

    2008-01-01T23:59:59.000Z

    Our lab identified the tandem BRCT domains of PTIP function as a DNA damage responsive phospho binding domain that recognizes proteins phosphorylated by ATM and ATR after DNA damage. The PTIP tandem BRCT domains are ...

  6. A Cysteine-Rich CCG Domain Contains a Novel [4Fe-4S] Cluster Binding Motif As Deduced From Studies With Subunit B of Heterodisulfide Reductase From Methanothermobacter Marburgensis

    SciTech Connect (OSTI)

    Hamann, N.; Mander, G.J.; Shokes, J.E.; Scott, R.A.; Bennati, M.; Hedderich, R.

    2009-06-01T23:59:59.000Z

    Heterodisulfide reductase (HDR) of methanogenic archaea with its active-site [4Fe-4S] cluster catalyzes the reversible reduction of the heterodisulfide (CoM-S-S-CoB) of the methanogenic coenzyme M (CoM-SH) and coenzyme B (CoB-SH). CoM-HDR, a mechanistic-based paramagnetic intermediate generated upon half-reaction of the oxidized enzyme with CoM-SH, is a novel type of [4Fe-4S]{sup 3+} cluster with CoM-SH as a ligand. Subunit HdrB of the Methanothermobacter marburgensis HdrABC holoenzyme contains two cysteine-rich sequence motifs (CX{sub 31-39}CCX{sub 35-36}CXXC), designated as CCG domain in the Pfam database and conserved in many proteins. Here we present experimental evidence that the C-terminal CCG domain of HdrB binds this unusual [4Fe-4S] cluster. HdrB was produced in Escherichia coli, and an iron-sulfur cluster was subsequently inserted by in vitro reconstitution. In the oxidized state the cluster without the substrate exhibited a rhombic EPR signal (g{sub zyx} = 2.015, 1.995, and 1.950) reminiscent of the CoM-HDR signal. {sup 57}Fe ENDOR spectroscopy revealed that this paramagnetic species is a [4Fe-4S] cluster with {sup 57}Fe hyperfine couplings very similar to that of CoM-HDR. CoM-{sup 33}SH resulted in a broadening of the EPR signal, and upon addition of CoM-SH the midpoint potential of the cluster was shifted to values observed for CoM-HDR, both indicating binding of CoM-SH to the cluster. Site-directed mutagenesis of all 12 cysteine residues in HdrB identified four cysteines of the C-terminal CCG domain as cluster ligands. Combined with the previous detection of CoM-HDR-like EPR signals in other CCG domain-containing proteins our data indicate a general role of the C-terminal CCG domain in coordination of this novel [4Fe-4S] cluster. In addition, Zn K-edge X-ray absorption spectroscopy identified an isolated Zn site with an S{sub 3}(O/N){sub 1} geometry in HdrB and the HDR holoenzyme. The N-terminal CCG domain is suggested to provide ligands to the Zn site.

  7. Crystallization of an engineered RUN domain of Rab6-interacting protein 1/DENND5

    SciTech Connect (OSTI)

    Fernandes, Humberto; Franklin, Edward; Khan, Amir R. (Trinity)

    2011-08-29T23:59:59.000Z

    Effectors of the Rab small GTPases are large multi-domain proteins which have proved difficult to express in soluble form in Escherichia coli. Generally, effectors are recruited to a distinct subcellular compartment by active (GTP-bound) Rabs, which are linked to membranes by one or two prenylated Cys residues at their C-termini. Following recruitment via their Rab-binding domain (RBD), effectors carry out various aspects of vesicle formation, transport, tethering and fusion through their other domains. Previously, successful purification of the RUN-PLAT tandem domains (residues 683-1061) of the 1263-residue Rab6-interacting protein 1 (R6IP1) required co-expression with Rab6, as attempts to solubly express the effector alone were unsuccessful. R6IP1 is also known as DENN domain-containing protein 5 (DENND5) and is expressed as two isoforms, R6IP1A/B (DENND5A/B), which differ by 24 amino acids at the N-terminus. Here, a deletion in R6IP1 was engineered to enable soluble expression and to improve the quality of the crystals grown in complex with Rab6. A large 23-residue loop linking two -helices in the RUN1 domain was removed and replaced with a short linker. This loop resides on the opposite face to the Rab6-binding site and is not conserved in the RUN-domain family. In contrast to wild-type R6IP1-Rab6 crystals, which took several weeks to grow to full size, the engineered R6IP1 (RPdel)-Rab6 crystals could be grown in a matter of days.

  8. Synthetic heparin-binding growth factor analogs

    DOE Patents [OSTI]

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

    2007-01-23T23:59:59.000Z

    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.

  9. 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

    E-Print Network [OSTI]

    Pretto, Dalyir I.

    2010-01-01T23:59:59.000Z

    Regulatory functions of the N-terminal domain of the 70-kDaactivity of the three N-terminal domains of the largeA: global fold of the N-terminal RPA-70 domain reveals a

  10. Method for introducing unidirectional nested deletions

    DOE Patents [OSTI]

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

    2001-01-01T23:59:59.000Z

    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.

  11. Investigation of metal binding properties in the hairpin ribozyme

    E-Print Network [OSTI]

    Kirchner, Alyson Jane

    2002-01-01T23:59:59.000Z

    independently folding domains, labeled loop A and loop B. Divalent metal ions are thought to bind in specific sites within the structure and promote ribozyme folding, substrate binding, and cleavage. The goals of the present studies are to further clarify...

  12. Concrete Domains

    E-Print Network [OSTI]

    Kahn, Gilles; Plotkin, Gordon

    1993-01-01T23:59:59.000Z

    This paper introduces the theory of a particular kind of computation domains called concrete domains. The purpose of this theory is to find a satisfactory framework for the notions of coroutine computation and sequentiality ...

  13. Synthetic heparin-binding factor analogs

    DOE Patents [OSTI]

    Pena, Louis A. (Poquott, NY); Zamora, Paul O. (Gaithersburg, MD); Lin, Xinhua (Plainview, NY); Glass, John D. (Shoreham, NY)

    2010-04-20T23:59:59.000Z

    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.

  14. An environment-mediated quantum deleter

    E-Print Network [OSTI]

    R. Srikanth; Subhashish Banerjee

    2007-04-24T23:59:59.000Z

    Environment-induced decoherence presents a great challenge to realizing a quantum computer. We point out the somewhat surprising fact that decoherence can be useful, indeed necessary, for practical quantum computation, in particular, for the effective erasure of quantum memory in order to initialize the state of the quantum computer. The essential point behind the deleter is that the environment, by means of a dissipative interaction, furnishes a contractive map towards a pure state. We present a specific example of an amplitude damping channel provided by a two-level system's interaction with its environment in the weak Born-Markov approximation. This is contrasted with a purely dephasing, non-dissipative channel provided by a two-level system's interaction with its environment by means of a quantum nondemolition interaction. We point out that currently used state preparation techniques, for example using optical pumping, essentially perform as quantum deleters.

  15. Interaction between the Conserved Region in the C-terminal Domain of GRK2 and Rhodopsin Is Necessary for GRK2 to

    E-Print Network [OSTI]

    Tian, Weidong

    Interaction between the Conserved Region in the C-terminal Domain of GRK2 and Rhodopsin Sciences, Shanghai 200031, People's Republic of China The C-terminal domain of G protein-coupled receptor by the conserved region. Truncation of the C-terminal domain or deletion of the conserved region in this domain

  16. Financial Opportunities Delete Me | Department of Energy

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

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative Fuels Data Center Home Page on Google Bookmark EERE: Alternative Fuels DataDepartment of Energy Your Density Isn't YourTransport inEnergy June 6-7, 2013 MeetingEA # 1440 FINALbyFinancial Opportunities Delete

  17. Method for introducing unidirectional nested deletions

    DOE Patents [OSTI]

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

    1999-07-27T23:59:59.000Z

    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.

  18. Method for introducing unidirectional nested deletions

    DOE Patents [OSTI]

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

    1999-07-27T23:59:59.000Z

    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.

  19. Uterine deletion of Trp53 compromises antioxidant responses in...

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

    clearly understood. From our recent finding that premature decidual senescence with terminal differentiation is a cause of preterm birth in mice with uterine Trp53 deletion,...

  20. Polypyrimidine Track-binding Protein Binding Downstream of Caspase-2 Alternative Exon 9 Represses Its Inclusion*

    E-Print Network [OSTI]

    Wu, Jane Y.

    Polypyrimidine Track-binding Protein Binding Downstream of Caspase-2 Alternative Exon 9 Represses (In100) located in the intron downstream of alternative exon 9. The upstream portion of this element downstream from the decoy 3 acceptor site. This downstream domain harbors several polypyrimidine track

  1. Multi-omic data integration links Deleted in Breast Cancer 1...

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

    omic data integration links Deleted in Breast Cancer 1 (DBC1) Degradation to Chromatin Remodeling in Inflammatory Response Multi-omic data integration links Deleted in Breast...

  2. ?-Tubulin and the C-terminal motor domain kinesin-like protein, KLPA, function in the establishment of spindle bipolarity in Aspergillus nidulans

    E-Print Network [OSTI]

    Prigozhina, Natalie L.; Walker, Richard A.; Oakley, C. Elizabeth; Oakley, Berl R.

    2001-10-01T23:59:59.000Z

    Previous research has found that a ?-tubulin mutation inSchizosaccharomyces pombe is synthetically lethal with a deletion of the C-terminal motor domain kinesin-like protein genepkl1, but the lethality of the double mutant ...

  3. Fitness Uniform Deletion: A Simple Way to Preserve Diversity

    E-Print Network [OSTI]

    Hutter, Marcus

    is the gradual decline in population diversity that tends to occur over time. This can slow a system's progress. In this paper we present the Fitness Uniform Deletion Scheme (FUDS), a simple but somewhat unconventional ap

  4. The Membrane-anchoring Domain of Epidermal Growth Factor Receptor...

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

    with different domains of both EGF and HB-EGF. We found that ligands having the N-terminal extension of EGF could not bind to the EGFR, even when released from the membrane....

  5. Eminent Domain Law (Iowa)

    Broader source: Energy.gov [DOE]

    These regulations confer the power of eminent domain and describe procedures for exercising eminent domain in Iowa.

  6. Dual chain synthetic heparin-binding growth factor analogs

    DOE Patents [OSTI]

    Zamora, Paul O. (Gaithersburg, MD); Pena, Louis A. (Poquott, NY); Lin, Xinhua (Plainview, NY)

    2012-04-24T23:59:59.000Z

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

  7. Dual chain synthetic heparin-binding growth factor analogs

    DOE Patents [OSTI]

    Zamora, Paul O. (Gaithersburg, MD); Pena, Louis A. (Poquott, NY); Lin, Xinhua (Plainview, NY)

    2009-10-06T23:59:59.000Z

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

  8. DMBC: Domain Names & Web Hosting Domain Names

    E-Print Network [OSTI]

    Stowell, Michael

    DMBC: Domain Names & Web Hosting Domain Names Top Level Domains · .com · .net · .org · .edu · .gov.9% of the web-viewing audience is used to typing in. Chances are, a visitor will type in ".com" even if you tell and simple · Try to avoid dashes or underscores in the domain name unless there is no other option Web

  9. Delivering Heparin-Binding Insulin-Like Growth Factor 1 with Self-Assembling Peptide Hydrogels

    E-Print Network [OSTI]

    Miller, Rachel E.

    Heparin-binding insulin-like growth factor 1 (HB-IGF-1) is a fusion protein of IGF-1 with the HB domain of heparin-binding epidermal growth factor-like growth factor. A single dose of HB-IGF-1 has been shown to bind ...

  10. Find It. Delete It. Protect It. Information Technology Security Strategy

    E-Print Network [OSTI]

    Sheridan, Jennifer

    Find It. Delete It. Protect It. Information Technology Security Strategy Executive Summary The general proposed strategy is to optimize risk management for information security incrementally and over that security will be a process rather than project. Achievement of the goal, optimized risk management

  11. Global Systems-Level Analysis of Hfq and SmpB Deletion Mutants...

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

    Systems-Level Analysis of Hfq and SmpB Deletion Mutants in Salmonella: Implications for Virulence and Global Protein Global Systems-Level Analysis of Hfq and SmpB Deletion Mutants...

  12. Quantum Fusion of Domain Walls with Fluxes

    E-Print Network [OSTI]

    S. Bolognesi; M. Shifman; M. B. Voloshin

    2009-07-20T23:59:59.000Z

    We study how fluxes on the domain wall world volume modify quantum fusion of two distant parallel domain walls into a composite wall. The elementary wall fluxes can be separated into parallel and antiparallel components. The parallel component affects neither the binding energy nor the process of quantum merger. The antiparallel fluxes, instead, increase the binding energy and, against naive expectations, suppress quantum fusion. In the small flux limit we explicitly find the bounce solution and the fusion rate as a function of the flux. We argue that at large (antiparallel) fluxes there exists a critical value of the flux (versus the difference in the wall tensions), which switches off quantum fusion altogether. This phenomenon of flux-related wall stabilization is rather peculiar: it is unrelated to any conserved quantity. Our consideration of the flux-related all stabilization is based on substantiated arguments that fall short of complete proof.

  13. atp binding domain: Topics by E-print Network

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

    corroborate asymmetry of catalysis in F0F1-ATP synthase. Zarrabi, Nawid; Diez, Manuel; Graeber, Peter; Wrachtrup, Joerg; Boersch, Michael 2007-01-01 157 Molecular composition of...

  14. Evaluation of selected binding domains for the analysis of ubiquitinat...

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

    been shown to be involved in many critical eukaryotic cellular functions. Affinity enrichment of ubiquitinated proteins has enabled the global analysis of this key modification....

  15. Structural basis for the evolutionary inactivation of Ca[superscript 2+] binding to synaptotagmin 4

    SciTech Connect (OSTI)

    Dai, Han; Shin, Ok-Ho; Machius, Mischa; Tomchick, Diana R.; Sdhof, Thomas C.; Rizo, Josep (U. of Texas-SMED)

    2010-11-16T23:59:59.000Z

    The neuronal protein synaptotagmin 1 functions as a Ca{sup 2+} sensor in exocytosis via two Ca{sup 2+}-binding C{sub 2} domains. The very similar synaptotagmin 4, which includes all the predicted Ca{sup 2+}-binding residues in the C{sub 2}B domain but not in the C{sub 2}A domain, is also thought to function as a neuronal Ca{sup 2+} sensor. Here we show that, unexpectedly, both C{sub 2} domains of fly synaptotagmin 4 exhibit Ca{sup 2+}-dependent phospholipid binding, whereas neither C{sub 2} domain of rat synaptotagmin 4 binds Ca{sup 2+} or phospholipids efficiently. Crystallography reveals that changes in the orientations of critical Ca{sup 2+} ligands, and perhaps their flexibility, render the rat synaptotagmin 4 C{sub 2}B domain unable to form full Ca{sup 2+}-binding sites. These results indicate that synaptotagmin 4 is a Ca{sup 2+} sensor in the fly but not in the rat, that the Ca{sup 2+}-binding properties of C{sub 2} domains cannot be reliably predicted from sequence analyses, and that proteins clearly identified as orthologs may nevertheless have markedly different functional properties.

  16. 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 (GSKPA)

    2014-10-02T23:59:59.000Z

    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.

  17. The solution structure of the amino-terminal HHCC domain of HIV-2 integrase: a three-helix bundle stabilized by zinc

    E-Print Network [OSTI]

    Tullius, Thomas D.

    The solution structure of the amino-terminal HHCC domain of HIV-2 integrase: a three-helix bundle to phosphates in the target DNA. Three domains have been identified in HIV integrase: an amino-terminal domain, a central catalytic core and a carboxy- terminal DNA-binding domain. The amino-terminal region is the only

  18. Nucleotide binding and conformational switching in the hexameric ring of a AAA+ machine

    E-Print Network [OSTI]

    Stinson, Benjamin M. (Benjamin Michael)

    2015-01-01T23:59:59.000Z

    ATP-powered proteases enforce protein quality-control and regulation in all domains of life. ClpX, a AAA+ ring homohexamer, uses the energy of ATP binding and hydrolysis to power conformational changes that unfold and ...

  19. Topological Domain Theory

    E-Print Network [OSTI]

    Battenfeld, Ingo

    2008-01-01T23:59:59.000Z

    This thesis presents Topological Domain Theory as a powerful and flexible framework for denotational semantics. Topological Domain Theory models a wide range of type constructions and can interpret many computational features. Furthermore, it has...We begin by describing the categories of Topological Domain Theory, and their categorical structure. In particular, we recover the basic constructions of domain theory, such as products, function spaces, fixed points and recursive types, in the context of Topological Domain Theory....As a central contribution, we give a detailed account of how computational effects can be modelled in Topological Domain Theory. Following recent work of Plotkin and Power, who proposed to construct effect monads via free algebra functors, this is done by showing that free algebras for a large class of parametrised equational theories exist in Topological Domain Theory. These parametrised equational theories are expressive enough to generate most of the standard examples of effect monads. Moreover, the free algebras in Topological Domain Theory are obtained by an explicit inductive construction, using only basic topological and set-theoretical principles....We also give a comparison of Topological and Classical Domain Theory. The category of omega-continuous dcpos embeds into Topological Domain Theory, and we prove that this embedding preserves the basic domain-theoretic constructions in most cases. We show that the classical powerdomain constructions on omega-continuous dcpos, including the probabilistic powerdomain, can be recovered in Topological Domain Theory....Finally, we give a synthetic account of Topological Domain Theory. We show that Topological Domain Theory is a specific model of Synthetic Domain Theory in the realizability topos over Scott's graph model. We give internal characterisations of the categories of Topological Domain Theory in this realizability topos, and prove the corresponding categories to be internally complete and weakly small. This enables us to show that Topological Domain Theory can model the polymorphic lambda-calculus, and to obtain a richer collection of free algebras than those constructed earlier....In summary, this thesis shows that Topological Domain Theory supports a wide range of semantic constructions, including the standard domain-theoretic constructions, computational effects and polymorphism, all within a single setting....

  20. How to delete a table? | OpenEI Community

    Open Energy Info (EERE)

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative Fuels Data Center Home Page onYou are now leaving Energy.gov You are now leaving Energy.gov You are8COaBulkTransmissionSitingProcess.pdfGetecGtel Jump to:Pennsylvania:County, Wyoming: EnergyCareview|delete a table?

  1. Melanin-binding radiopharmaceuticals

    SciTech Connect (OSTI)

    Packer, S; Fairchild, R G; Watts, K P; Greenberg, D; Hannon, S J

    1980-01-01T23:59:59.000Z

    The scope of this paper is limited to an analysis of the factors that are important to the relationship of radiopharmaceuticals to melanin. While the authors do not attempt to deal with differences between melanin-binding vs. melanoma-binding, a notable variance is assumed. (PSB)

  2. DNA binding specificity of the p73 DNA-binding domain

    E-Print Network [OSTI]

    Tse, Pui Wah

    2011-01-01T23:59:59.000Z

    was analyzed using non- linear regression curve with thewas analyzed using non- linear regression curve with the

  3. DNA binding specificity of the p73 DNA-binding domain

    E-Print Network [OSTI]

    Tse, Pui Wah

    2011-01-01T23:59:59.000Z

    interactions of p53 with DNA: when flexibility serves2006). Structural basis of DNA recognition by p53 tetramers.Z. (2010). Diversity in DNA recognition by p53 revealed by

  4. DNA binding specificity of the p73 DNA-binding domain

    E-Print Network [OSTI]

    Tse, Pui Wah

    2011-01-01T23:59:59.000Z

    of DNA recognition by p53 tetramers. Mol Cell 22, 741-753.site as a self-assembled tetramer. Structure 18, 246- Chene,structure of a p53 core tetramer bound to DNA. Oncogene 28,

  5. Eminent Domain Rights (Florida)

    Broader source: Energy.gov [DOE]

    Developers of certain facilities, including dams to be used for hydropower, natural gas companies, wastewater systems, and coal pipelines, may be eligible to exercise eminent domain powers in...

  6. Eminent Domain (Indiana)

    Broader source: Energy.gov [DOE]

    Utilities, corporations, and gas storage facilities may invoke the law of eminent domain in certain circumstances, as provided for in this legislation.

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

    DOE Patents [OSTI]

    Freimuth, Paul I.

    2010-04-06T23:59:59.000Z

    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.

  8. The fork head transcription factor Hcm1p participates in the regulation of SPC110, which encodes the calmodulin-binding protein in the

    E-Print Network [OSTI]

    Davis, Trisha N.

    The fork head transcription factor Hcm1p participates in the regulation of SPC110, which encodes and abolish the ability of Hcm1p to act as a suppressor of calmodulin mutants. The promoter of SPC110 contains a match to the consensus binding site. Deletion of HCM1 does not affect the basal level of SPC110

  9. Enhanced Hydrogen Production in Escherichia coli Through Chemical Mutagenesis, Gene Deletion, and Transposon Mutagenesis

    E-Print Network [OSTI]

    Garzon Sanabria, Andrea Juliana

    2011-08-08T23:59:59.000Z

    ENHANCED HYDROGEN PRODUCTION IN ESCHERICHIA COLI THROUGH CHEMICAL MUTAGENESIS, GENE DELETION, AND TRANSPOSON MUTAGENESIS A Thesis by ANDREA JULIANA GARZON SANABRIA Submitted to the Office of Graduate Studies of Texas A...&M University in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE May 2010 Major Subject: Chemical Engineering ENHANCED HYDROGEN PRODUCTION IN ESCHERICHIA COLI THROUGH CHEMICAL MUTAGENESIS, GENE DELETION...

  10. Structures of Human Pumilio with Noncognate RNAs Reveal Molecular Mechanisms for Binding Promiscuity

    SciTech Connect (OSTI)

    Gupta,Y.; Nair, D.; Wharton, R.; Aggarwal, A.

    2008-01-01T23:59:59.000Z

    Pumilio is a founder member of the evolutionarily conserved Puf family of RNA-binding proteins that control a number of physiological processes in eukaryotes. A structure of human Pumilio (hPum) Puf domain bound to a Drosophila regulatory sequence showed that each Puf repeat recognizes a single nucleotide. Puf domains in general bind promiscuously to a large set of degenerate sequences, but the structural basis for this promiscuity has been unclear. Here, we describe the structures of hPum Puf domain complexed to two noncognate RNAs, CycBreverse and Puf5. In each complex, one of the nucleotides is ejected from the binding surface, in effect, acting as a 'spacer.' The complexes also reveal the plasticity of several Puf repeats, which recognize noncanonical nucleotides. Together, these complexes provide a molecular basis for recognition of degenerate binding sites, which significantly increases the number of mRNAs targeted for regulation by Puf proteins in vivo.

  11. C-terminal Deletions of the Escherichia coli RecA Protein CHARACTERIZATION OF IN VIVO AND IN VITRO EFFECTS*

    E-Print Network [OSTI]

    Cox, Michael M.

    C-terminal Deletions of the Escherichia coli RecA Protein CHARACTERIZATION OF IN VIVO AND IN VITRO, Madison, Wisconsin 53706 A set of C-terminal deletion mutants of the RecA protein of Escherichia coli. In vivo, the deletion of 13 to 17 C-terminal residues results in increased sensitivity to mitomycin C

  12. Axion domain wall baryogenesis

    E-Print Network [OSTI]

    Daido, Ryuji; Takahashi, Fuminobu

    2015-01-01T23:59:59.000Z

    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, $m \\simeq 10^8 -10^{13}$ GeV and $f \\simeq 10^{13} - 10^{16}$ GeV. Baryonic isocurvature perturbations are significantly suppressed in our model, in contrast to various spontaneous baryogenesis scenarios in the slow-roll regime. In particular, the axion domain wall baryogenesis is consistent with high-scale inflation which generates a large tensor-to-scalar ratio within the reach of future CMB B-mode experiments. We also discuss the gravitational waves produced by the domain wall annihilation and its implications for the future gravitational wave experiments.

  13. PAPER www.rsc.org/obc | Organic & Biomolecular Chemistry RNA binding and thiolytic stability of a quinoline-containing

    E-Print Network [OSTI]

    Beal, Peter A.

    as the intercalation domain. A quinoline-containing HTP is shown to bind selectively to duplex RNA binding sites influences the affinity of these compounds for RNA targets. Our original HTP design used 9- anilinoacridines a new HTP design that uses quinoline for intercalation. A high yielding synthesis to a new quinoline

  14. Phosphopeptide interactions with BRCA1 BRCT domains: More than just a motif

    E-Print Network [OSTI]

    Wu, Qian; Jubb, Harry; Blundell, Tom L.

    2015-02-17T23:59:59.000Z

    structure showsrepresentation of BRCT domain mainchain is in slate colour and the globular structure is nd MQ. Wu et al. / Progress in Biophysics aphosphopeptide binding tightens the structure of tandem BRCT domains. 3.1. The first and second anchors... 1 BRCT domains are in slate colour, Bach1 phosphopeptide in 1T29 is in pink, TopBP1 BRCT 7-8 BRCT domains are in green, Bach1 phosphopeptide in 3AL3 is in yellow, BRCA1-BRCT-only structure is in wheat. Polar interaction is indicated in grey dashed...

  15. 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)

    2014-05-07T23:59:59.000Z

    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.

  16. Crystal structure of the C-terminal domain of the RAP74 subunit of human transcription factor IIF

    SciTech Connect (OSTI)

    Kamada, Katsuhiko; De Angelis, Jacqueline; Roeder, Robert G.; Burley, Stephen K. (Rockefeller)

    2012-12-13T23:59:59.000Z

    The x-ray structure of a C-terminal fragment of the RAP74 subunit of human transcription factor (TF) IIF has been determined at 1.02-{angstrom} resolution. The {alpha}/{beta} structure is strikingly similar to the globular domain of linker histone H5 and the DNA-binding domain of hepatocyte nuclear factor 3{gamma} (HNF-3{gamma}), making it a winged-helix protein. The surface electrostatic properties of this compact domain differ significantly from those of bona fide winged-helix transcription factors (HNF-3{gamma} and RFX1) and from the winged-helix domains found within the RAP30 subunit of TFIIF and the {beta} subunit of TFIIE. RAP74 has been shown to interact with the TFIIF-associated C-terminal domain phosphatase FCP1, and a putative phosphatase binding site has been identified within the RAP74 winged-helix domain.

  17. Type I oculocutaneous albinism (OCA1) associated with a large deletion of the tyrosinase (TYR) gene

    SciTech Connect (OSTI)

    Spritz, R.A.; Wick, P.A.; Holmes, S.A.; Schnur, R.E. [Univ. of Wisconsin, Madison, WI (United States)]|[Children`s Hospital of Philadelphia, PA (United States)

    1994-09-01T23:59:59.000Z

    OCA1 is an autosomal recessive disorder in which the biosynthesis of melanin is reduced or absent in skin, hair, and eyes, due to deficient enzymatic activity of tyrosinase. TYR consists of 5 exons spanning over 65 kb at 11q14-q21. Analyses of TYR in >400 unrelated patients with OCA1 have identified more than 50 different point mutations; however, no large deletions have been detected. Here we report a large deletion of TYR in a Caucasian boy with OCA1B. Simultaneous SSCP/heteroduplex screening and DNA sequence analysis indicated that the patient was apparently homozygous for a previously described TYR mutation, adjacent to the 3` splice site of IVS2 (-7, t{r_arrow}a). To distinguish between possible gene deletion vs. maternal uniparental isodisomy, we characterized several chromosome 11 polymorphisms. Maternal uniparental isodisomy was excluded by the patient`s heterozygosity for alleles at D11S35 (11q21-122) and HBG2 (11p15.5). In addition, the patient failed to inherit paternal alleles at an MboI RFLP in exon 1 of TYR and at a TaqI RFLP in the promoter region of the gene. To detect a possible submicroscopic deletion, we performed quantitative Southern blot hybridization using a full length TYR cDNA. Compared with controls, both the patient and his father appeared deleted for two or three TYR-derived PstI fragments; the two TYRL-derived fragments appeared normal. These data indicate that the patient and his father have a partial TYR deletion, including at least exons 1, 2, and IVS2. Based on the organization of the gene, this deletion is at least 50 kb in size. The patient is thus hemizygous for the maternally-inherited mutation in IVS2, accounting for his OCA1B phenotype.

  18. Internal strain regulates the nucleotide binding site of the kinesin leading head

    E-Print Network [OSTI]

    Hyeon, Changbong; 10.1073/pnas.0610939104

    2009-01-01T23:59:59.000Z

    In the presence of ATP, kinesin proceeds along the protofilament of microtubule by alternated binding of two motor domains on the tubulin binding sites. Since the processivity of kinesin is much higher than other motor proteins, it has been speculated that there exists a mechanism for allosteric regulation between the two monomers. Recent experiments suggest that ATP binding to the leading head domain in kinesin is regulated by the rearward strain built on the neck-linker. We test this hypothesis by explicitly modeling a $C_{\\alpha}$-based kinesin structure whose both motor domains are bound on the tubulin binding sites. The equilibrium structures of kinesin on the microtubule show disordered and ordered neck-linker configurations for the leading and the trailing head, respectively. The comparison of the structures between the two heads shows that several native contacts present at the nucleotide binding site in the leading head are less intact than those in the binding site of the rear head. The network of n...

  19. Structure of the dimerization domain of DiGeorge critical region 8

    SciTech Connect (OSTI)

    Senturia, R.; Faller, M.; Yin, S.; Loo, J.A.; Cascio, D.; Sawaya, M.R.; Hwang, D.; Clubb, R.T.; Guo, F. (UCLA)

    2010-09-27T23:59:59.000Z

    Maturation of microRNAs (miRNAs, {approx}22nt) from long primary transcripts [primary miRNAs (pri-miRNAs)] is regulated during development and is altered in diseases such as cancer. The first processing step is a cleavage mediated by the Microprocessor complex containing the Drosha nuclease and the RNA-binding protein DiGeorge critical region 8 (DGCR8). We previously reported that dimeric DGCR8 binds heme and that the heme-bound DGCR8 is more active than the heme-free form. Here, we identified a conserved dimerization domain in DGCR8. Our crystal structure of this domain (residues 298-352) at 1.7 {angstrom} resolution demonstrates a previously unknown use of a WW motif as a platform for extensive dimerization interactions. The dimerization domain of DGCR8 is embedded in an independently folded heme-binding domain and directly contributes to association with heme. Heme-binding-deficient DGCR8 mutants have reduced pri-miRNA processing activity in vitro. Our study provides structural and biochemical bases for understanding how dimerization and heme binding of DGCR8 may contribute to regulation of miRNA biogenesis.

  20. Production of glycoprotein-deleted rabies viruses for monosynaptic tracing and high-level gene expression in neurons

    E-Print Network [OSTI]

    Wickersham, Ian R.

    Recombinant rabies viruses rendered replication-deficient by the deletion of their envelope glycoprotein gene are useful tools for neuroscientists, permitting (1) extraordinarily high transgene expression levels within ...

  1. Domain analysis for estrogen receptor/Sp1-mediated transactivation and detection of estrogen receptor/Sp1 protein interactions in living cells

    E-Print Network [OSTI]

    Kim, KyoungHyun

    2005-11-01T23:59:59.000Z

    Estrogen Receptor ? (ER?)/Sp1 activation of GC-rich gene promoters in breast cancer cells is dependent, in part, on the activation function 1 (AF1) of ER?. This study investigates contributions of the DNA binding domain ...

  2. Multifunctionalities driven by ferroic domains

    SciTech Connect (OSTI)

    Yang, J. C.; Huang, Y. L.; Chu, Y. H., E-mail: yhc@nctu.edu.tw [Department of Materials Science and Engineering, National Chiao Tung University, Hsinchu 30010, Taiwan (China); He, Q. [Department of Physics, Durham University, Durham DH1 3LE (United Kingdom)

    2014-08-14T23:59:59.000Z

    Considerable attention has been paid to ferroic systems in pursuit of advanced applications in past decades. Most recently, the emergence and development of multiferroics, which exhibit the coexistence of different ferroic natures, has offered a new route to create functionalities in the system. In this manuscript, we step from domain engineering to explore a roadmap for discovering intriguing phenomena and multifunctionalities driven by periodic domain patters. As-grown periodic domains, offering exotic order parameters, periodic local perturbations and the capability of tailoring local spin, charge, orbital and lattice degrees of freedom, are introduced as modeling templates for fundamental studies and novel applications. We discuss related significant findings on ferroic domain, nanoscopic domain walls, and conjunct heterostructures based on the well-organized domain patterns, and end with future prospects and challenges in the field.

  3. Deleting species from model food webs Christopher Quince, Paul G. Higgs and Alan J. McKane

    E-Print Network [OSTI]

    McKane, Alan

    causing extinction of further species from the food web. To investigate these effects we used one species was deleted. On average, only 2.1% of the remaining species went extinct as a result of extinction. The probability of extinction of prey of the deleted species was also significantly higher than

  4. Domain walls in gapped graphene

    E-Print Network [OSTI]

    G. W. Semenoff; V. Semenoff; Fei Zhou

    2008-05-31T23:59:59.000Z

    The electronic properties of a particular class of domain walls in gapped graphene are investigated. We show that they can support mid-gap states which are localized in the vicinity of the domain wall and propagate along its length. With a finite density of domain walls, these states can alter the electronic properties of gapped graphene significantly. If the mid-gap band is partially filled,the domain wall can behave like a one-dimensional metal embedded in a semi-conductor, and could potentially be used as a single-channel quantum wire.

  5. Domain walls in gapped graphene

    E-Print Network [OSTI]

    Semenoff, G W; Zhou, Fei

    2015-01-01T23:59:59.000Z

    The electronic properties of a particular class of domain walls in gapped graphene are investigated. We show that they can support mid-gap states which are localized in the vicinity of the domain wall and propagate along its length. With a finite density of domain walls, these states can alter the electronic properties of gapped graphene significantly. If the mid-gap band is partially filled,the domain wall can behave like a one-dimensional metal embedded in a semi-conductor, and could potentially be used as a single-channel quantum wire.

  6. Development/Plasticity/Repair Deletion of ERK2 Mitogen-Activated Protein Kinase

    E-Print Network [OSTI]

    Development/Plasticity/Repair Deletion of ERK2 Mitogen-Activated Protein Kinase Identifies Its Key University, Piscataway, New Jersey 08855-8082 The mitogen-activated protein (MAP) kinases ERK1 and ERK2-specific functions in vivo. We have examined the role of ERK2 in neural development by conditional inactivation

  7. Evaluation of unmarked deletion mutants as improved Brucella vaccine strains in the mouse and goat models

    E-Print Network [OSTI]

    Kahl, Melissa Marie

    2006-10-30T23:59:59.000Z

    and in vitro virulence. Survival and efficacy of these novel deletion mutants were then evaluated in the mouse model. The asp24 mutants, which persist for extended periods in vivo, appear superior as a vaccine candidate compared to approved vaccine strains S19...

  8. The Frequency of DYT1 (GAG Deletion) Mutation in Primary Dystonia Patients from Iran

    E-Print Network [OSTI]

    Boyer, Edmond

    The Frequency of DYT1 (GAG Deletion) Mutation in Primary Dystonia Patients from Iran Mohammad Hamid. Molecular Medicine Division, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran 2. Medical Genetics Department, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran 3

  9. DeltaSky: Optimal Maintenance of Skyline Deletions without Exclusive Dominance Region Generation

    E-Print Network [OSTI]

    Egecioglu, ?mer

    of the so called exclusive dominance region (EDR) to achieve optimal I/O performance for deletion maintenance. However, the shape of an EDR becomes extremely complex in higher dimensions, and algorithms for its computation have not been developed. We derive a systematic way to decompose a d-dimensional EDR

  10. MHC Class II Tetramers and the Pursuit of Antigen-specific T cells: Define, Deviate, Delete

    E-Print Network [OSTI]

    Paris-Sud XI, Universit de

    1 MHC Class II Tetramers and the Pursuit of Antigen-specific T cells: Define, Deviate, Delete Class II tetramers Corresponding Author: Roberto Mallone, MD Benaroya Research Institute at Virginia secretion and proliferation. The advent of MHC Class II tetramers has added a pivotal tool to our research

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

    SciTech Connect (OSTI)

    Yasunaga, Mai; Ipsaro, Jonathan J.; Mondragn, Alfonso (NWU)

    2014-10-02T23:59:59.000Z

    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.

  12. Determining the Intrinsic Properties of the C1B Domain that Influence PKC Ligand Specificity and Sensitivity to Reactive Oxygen Species

    E-Print Network [OSTI]

    Stewart, Mikaela D.

    2013-06-04T23:59:59.000Z

    activity, these studies probe the structure, dynamics, and reactivity of one of the domains responsible for PKC regulation, C1B. C1B binds signaling molecules and translocates PKC to membranes in order to release the kinase domain from inhibition...

  13. The EIIIA domain from astrocyte-derived fibronectin mediates proliferation of oligodendrocyte progenitor cells following CNS demyelination

    E-Print Network [OSTI]

    Stoffels, Josephine M. J.; Hoekstra, Dick; Franklin, Robin J. M.; Baron, Wia; Zhao, Chao

    2014-08-25T23:59:59.000Z

    an alternative mechanism.This mechanism may involve other domains of Fn, since alternative splicing of Fn can change the conformation of Fn, affecting the presentation of binding sequences and exposing cryptic binding sites(Pickford and Campbell, 2004; Ventura... -EDA promotes survival and prevents adverse remodeling and heart function deterioration after myocardial infarction. Circ Res 108:582-592. Balza E, Sassi F, Ventura E, Parodi A, Fossati S, Blalock W, Carnemolla B, Castellani P, Zardi L, Borsi L (2009) A...

  14. The N-terminus of TDP-43 promotes its oligomerization and enhances DNA binding affinity

    SciTech Connect (OSTI)

    Chang, Chung-ke [Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan (China)] [Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan (China); Wu, Tzong-Huah [Institute of Chemistry, Academia Sinica, Taipei 115, Taiwan (China) [Institute of Chemistry, Academia Sinica, Taipei 115, Taiwan (China); Chemical Biology and Molecular Biophysics Program, Taiwan International Graduate Program, Institute of Biochemistry, Academia Sinica, Taipei 115, Taiwan (China); Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu 300, Taiwan (China); Wu, Chu-Ya [Institute of Chemistry, Academia Sinica, Taipei 115, Taiwan (China) [Institute of Chemistry, Academia Sinica, Taipei 115, Taiwan (China); Graduate Institute of Engineering, National Taiwan University of Science and Technology, Taipei 106, Taiwan (China); Chiang, Ming-hui; Toh, Elsie Khai-Woon [Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan (China)] [Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan (China); Hsu, Yin-Chih; Lin, Ku-Feng [Institute of Chemistry, Academia Sinica, Taipei 115, Taiwan (China)] [Institute of Chemistry, Academia Sinica, Taipei 115, Taiwan (China); Liao, Yu-heng [Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan (China)] [Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan (China); Huang, Tai-huang, E-mail: bmthh@gate.sinica.edu.tw [Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan (China) [Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan (China); Department of Physics, National Taiwan Normal University, Taipei 106, Taiwan (China); Huang, Joseph Jen-Tse, E-mail: jthuang@chem.sinica.edu.tw [Institute of Chemistry, Academia Sinica, Taipei 115, Taiwan (China)

    2012-08-24T23:59:59.000Z

    Highlights: Black-Right-Pointing-Pointer The N-terminus of TDP-43 contains an independently folded structural domain (NTD). Black-Right-Pointing-Pointer The structural domains of TDP-43 are arranged in a beads-on-a-string fashion. Black-Right-Pointing-Pointer The NTD promotes TDP-43 oligomerization in a concentration-dependent manner. Black-Right-Pointing-Pointer The NTD may assist nucleic acid-binding activity of TDP-43. -- Abstract: TDP-43 is a DNA/RNA-binding protein associated with different neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD-U). Here, the structural and physical properties of the N-terminus on TDP-43 have been carefully characterized through a combination of nuclear magnetic resonance (NMR), circular dichroism (CD) and fluorescence anisotropy studies. We demonstrate for the first time the importance of the N-terminus in promoting TDP-43 oligomerization and enhancing its DNA-binding affinity. An unidentified structural domain in the N-terminus is also disclosed. Our findings provide insights into the N-terminal domain function of TDP-43.

  15. GABA{sub A} receptor open-state conformation determines non-competitive antagonist binding

    SciTech Connect (OSTI)

    Chen Ligong [Environmental Chemistry and Toxicology Laboratory, Department of Environmental Science, Policy and Management, University of California, Berkeley, CA 94720 (United States); Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA 94158 (United States); Xue Ling [Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720 (United States); Giacomini, Kathleen M. [Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA 94158 (United States); Casida, John E., E-mail: ectl@berkeley.edu [Environmental Chemistry and Toxicology Laboratory, Department of Environmental Science, Policy and Management, University of California, Berkeley, CA 94720 (United States)

    2011-02-01T23:59:59.000Z

    The {gamma}-aminobutyric acid (GABA) type A receptor (GABA{sub A}R) is one of the most important targets for insecticide action. The human recombinant {beta}3 homomer is the best available model for this binding site and 4-n-[{sup 3}H]propyl-4'-ethynylbicycloorthobenzoate ([{sup 3}H]EBOB) is the preferred non-competitive antagonist (NCA) radioligand. The uniquely high sensitivity of the {beta}3 homomer relative to the much-less-active but structurally very-similar {beta}1 homomer provides an ideal comparison to elucidate structural and functional features important for NCA binding. The {beta}1 and {beta}3 subunits were compared using chimeragenesis and mutagenesis and various combinations with the {alpha}1 subunit and modulators. Chimera {beta}3/{beta}1 with the {beta}3 subunit extracellular domain and the {beta}1 subunit transmembrane helices retained the high [{sup 3}H]EBOB binding level of the {beta}3 homomer while chimera {beta}1/{beta}3 with the {beta}1 subunit extracellular domain and the {beta}3 subunit transmembrane helices had low binding activity similar to the {beta}1 homomer. GABA at 3 {mu}M stimulated heteromers {alpha}1{beta}1 and {alpha}1{beta}3 binding levels more than 2-fold by increasing the open probability of the channel. Addition of the {alpha}1 subunit rescued the inactive {beta}1/{beta}3 chimera close to wildtype {alpha}1{beta}1 activity. EBOB binding was significantly altered by mutations {beta}1S15'N and {beta}3N15'S compared with wildtype {beta}1 and {beta}3, respectively. However, the binding activity of {alpha}1{beta}1S15'N was insensitive to GABA and {alpha}1{beta}3N15'S was stimulated much less than wildtype {alpha}1{beta}3 by GABA. The inhibitory effect of etomidate on NCA binding was reduced more than 5-fold by the mutation {beta}3N15'S. Therefore, the NCA binding site is tightly regulated by the open-state conformation that largely determines GABA{sub A} receptor sensitivity. - Graphical Abstract: Display Omitted Research Highlights: > The {beta}1 and {beta}3 subunits were compared by chimeragenesis, mutagenesis and modulators. > Low {beta}1 NCA binding was rescued by replacing its transmembrane helices with those of {beta}3. > GABA at 3 {mu}M stimulated heteromers {alpha}1{beta}1 and {alpha}1{beta}3 binding levels more than 2-fold. > Mutation at 15' position in TM2 reduced GABA stimulation of NCA binding. > The open-state conformation largely determines GABAA receptor sensitivity to NCAs.

  16. Domain architecture and oligomerization properties of the paramyxovirus PIV 5 hemagglutinin-neuraminidase (HN) protein

    SciTech Connect (OSTI)

    Yuan Ping [Department of Structural Biology, Stanford University, Palo Alto, CA 94305-5126 (United States); Leser, George P. [Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, IL 60208-3500 (United States); Demeler, Borries [Department of Biochemistry, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229-3901 (United States); Lamb, Robert A. [Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, IL 60208-3500 (United States); Howard Hughes Medical Institute, Northwestern University, Evanston, IL 60208-3500 (United States); Jardetzky, Theodore S. [Department of Structural Biology, Stanford University, Palo Alto, CA 94305-5126 (United States)], E-mail: tjardetz@stanford.edu

    2008-09-01T23:59:59.000Z

    The mechanism by which the paramyxovirus hemagglutinin-neuraminidase (HN) protein couples receptor binding to activation of virus entry remains to be fully understood, but the HN stalk is thought to play an important role in the process. We have characterized ectodomain constructs of the parainfluenza virus 5 HN to understand better the underlying architecture and oligomerization properties that may influence HN functions. The PIV 5 neuraminidase (NA) domain is monomeric whereas the ectodomain forms a well-defined tetramer. The HN stalk also forms tetramers and higher order oligomers with high {alpha}-helical content. Together, the data indicate that the globular NA domains form weak intersubunit interactions at the end of the HN stalk tetramer, while stabilizing the stalk and overall oligomeric state of the ectodomain. Electron microscopy of the HN ectodomain reveals flexible arrangements of the NA and stalk domains, which may be important for understanding how these two HN domains impact virus entry.

  17. Domain walls riding the wave.

    SciTech Connect (OSTI)

    Karapetrov, G.; Novosad, V.; Materials Science Division

    2010-11-01T23:59:59.000Z

    Recent years have witnessed a rapid proliferation of electronic gadgets around the world. These devices are used for both communication and entertainment, and it is a fact that they account for a growing portion of household energy consumption and overall world consumption of electricity. Increasing the energy efficiency of these devices could have a far greater and immediate impact than a gradual switch to renewable energy sources. The advances in the area of spintronics are therefore very important, as gadgets are mostly comprised of memory and logic elements. Recent developments in controlled manipulation of magnetic domains in ferromagnet nanostructures have opened opportunities for novel device architectures. This new class of memories and logic gates could soon power millions of consumer electronic devices. The attractiveness of using domain-wall motion in electronics is due to its inherent reliability (no mechanical moving parts), scalability (3D scalable architectures such as in racetrack memory), and nonvolatility (retains information in the absence of power). The remaining obstacles in widespread use of 'racetrack-type' elements are the speed and the energy dissipation during the manipulation of domain walls. In their recent contribution to Physical Review Letters, Oleg Tretiakov, Yang Liu, and Artem Abanov from Texas A&M University in College Station, provide a theoretical description of domain-wall motion in nanoscale ferromagnets due to the spin-polarized currents. They find exact conditions for time-dependent resonant domain-wall movement, which could speed up the motion of domain walls while minimizing Ohmic losses. Movement of domain walls in ferromagnetic nanowires can be achieved by application of external magnetic fields or by passing a spin-polarized current through the nanowire itself. On the other hand, the readout of the domain state is done by measuring the resistance of the wire. Therefore, passing current through the ferromagnetic wire is the preferred method, as it combines manipulation and readout of the domain-wall state. The electrons that take part in the process of readout and manipulation of the domain-wall structure in the nanowire do so through the so-called spin transfer torque: When spin-polarized electrons in the ferromagnet nanowire pass through the domain wall they experience a nonuniform magnetization, and they try to align their spins with the local magnetic moments. The force that the electrons experience has a reaction force counterpart that 'pushes' the local magnetic moments, resulting in movement of the domain wall in the direction of the electron flow through the spin-transfer torque. The forces between the electrons and the local magnetic moments in the ferromagnet also create additional electrical resistance for the electrons passing through the domain wall. By measuring resistance across a segment of the nanowire, one determines if a domain wall is present; i.e., one can read the stored information. The interaction of the spin-polarized electrons with the domain wall in the ferromagnetic nanowire is not very efficient. Even for materials achieving high polarization of the free electrons, it is very difficult to move the magnetic domain wall. Several factors contribute to this problem, with imperfections of the ferromagnetic nanowire that cause domain-wall pinning being the dominant one. Permalloy nanowires, one of the best candidates for domain-wall-based memory and logic devices, require current densities of the order of 10{sup 8} A/cm{sup 2} in order to move a domain wall from a pinning well. Considering that this current has to pass through a relatively long wire, it is not very difficult to imagine that most of the energy will go to Joule heating. The efficiency of the process - the ratio of the energy converted to domain-wall motion to the total energy consumed - is comparable to that of an incandescent light bulb converting electricity to light. A step towards more efficient domain-wall-based memory devices is the advance of using alternating currents or curren

  18. 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)

    2010-12-02T23:59:59.000Z

    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.

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

    Open Energy Info (EERE)

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative Fuels Data Center Home Page onYou are now leaving Energy.gov You are now leaving Energy.gov You are8COaBulkTransmissionSitingProcess.pdfGetecGtel Jump to:Pennsylvania:County, Wyoming: EnergyCareview|delete arecreate

  20. Erythropoietin binding protein from mammalian serum

    DOE Patents [OSTI]

    Clemons, Gisela K. (Berkeley, CA)

    1997-01-01T23:59:59.000Z

    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.

  1. Erythropoietin binding protein from mammalian serum

    DOE Patents [OSTI]

    Clemons, G.K.

    1997-04-29T23:59:59.000Z

    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.

  2. The Catalytic and GAF Domains of the Rod cGMP Phosphodiesterase (PDE6) Heterodimer Are Regulated by Distinct

    E-Print Network [OSTI]

    Cote, Rick H.

    M) when the regulatory GAF domains of bovine rod PDE6 are occupied by cGMP. Binding heterogeneity, and retard cGMP exchange with both noncatalytic sites. Subunit heterogeneity, multiple sites of interaction of the two active sites, further supporting the idea of catalytic subunit heterogeneity with respect to P

  3. The Insulator Binding Protein CTCF Positions 20 Nucleosomes around Its Binding Sites across the Human

    E-Print Network [OSTI]

    Weng, Zhiping

    The Insulator Binding Protein CTCF Positions 20 Nucleosomes around Its Binding Sites across occupied by the insulator binding protein CTCF across the human genome. These nucleosomes are highly of CTCF function. Citation: Fu Y, Sinha M, Peterson CL, Weng Z (2008) The Insulator Binding Protein CTCF

  4. A Rare Earth-DOTA-Binding Antibody: Probe Properties and Binding Affinity across the Lanthanide Series

    E-Print Network [OSTI]

    Fisher, Andrew J.

    1) binds transition metals and rare earths with extreme stability under physiological conditionsA Rare Earth-DOTA-Binding Antibody: Probe Properties and Binding Affinity across the Lanthanide affinity and exquisite specificity.1 An antibody that binds rare earth complexes selectively could be used

  5. Ligand binding proteins: roles in ligand transfer and activation of nuclear receptors

    E-Print Network [OSTI]

    Petrescu, Anca Daniela

    2004-09-30T23:59:59.000Z

    functions: steroidogenic acute regulatory protein (StAR), hepatocyte nuclear factor-4alpha (HNF-4alpha) and acyl-CoA binding protein (ACBP). First, StAR mediates delivery of cholesterol to inner mitochondrial membrane in steroidogenesis by a poorly... structure. Fluorescent sterol exchange assays between donor and acceptor mitochondrial membranes indicate that StAR significantly increased the formation of rapidly transferable cholesterol domains. Second, HNF-4alpha, a nuclear receptor, had been shown...

  6. proteinsSTRUCTURE O FUNCTION O BIOINFORMATICS Thermodynamics of calmodulin binding to

    E-Print Network [OSTI]

    Dokholyan, Nikolay V.

    and skeletal muscle ryanodine receptor ion channels Gerhard Meissner,* Daniel A. Pasek, Naohiro Yamaguchi . A no- table property of the RyRs is that they interact with both the Ca21 -free (apoCaM) and Ca21 to the intact receptors indi- cates that the RyRs have a single, high-affinity binding domain for apoCaM and Ca

  7. 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

    2004-01-07T23:59:59.000Z

    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.

  8. Characterizations of exchangeable partitions and random discrete distributions by deletion properties

    E-Print Network [OSTI]

    Gnedin, Alexander; Pitman, Jim

    2009-01-01T23:59:59.000Z

    We prove a long-standing conjecture which characterises the Ewens-Pitman two-parameter family of exchangeable random partitions, plus a short list of limit and exceptional cases, by the following property: for each $n = 2,3, >...$, if one of $n$ individuals is chosen uniformly at random, independently of the random partition $\\pi_n$ of these individuals into various types, and all individuals of the same type as the chosen individual are deleted, then for each $r > 0$, given that $r$ individuals remain, these individuals are partitioned according to $\\pi_r'$ for some sequence of random partitions $(\\pi_r')$ that does not depend on $n$ or $r$. An analogous result characterizes the associated Poisson-Dirichlet family of random discrete distributions by an independence property related to random deletion of a frequency chosen by a size-biased pick. We also survey the regenerative properties of members of the two-parameter family, and settle a question regarding the explicit arrangement of intervals with lengths ...

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

    E-Print Network [OSTI]

    Sosa, BrianA.

    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 ...

  10. Identification of the Ubiquinone-binding Domain in the Disulfide Catalyst Disulfide Bond Protein B*

    E-Print Network [OSTI]

    Bardwell, James

    of quinones. To explore the mechanism of this newly described enzymatic activity, we decided to study motif of DsbB is oxidized in the presence of a functional respiratory chain. This provides the firstA-DsbB system with purified electron transfer compo- nents in vitro, Bader et al. (7) identifies ubiquinone

  11. Topoisomerase II? Binding Domains of Adenomatous Polyposis Coli Influence Cell Cycle Progression and Aneuploidy

    E-Print Network [OSTI]

    Wang, Yang; Coffey, Robert J.; Osheroff, Neil; Neufeld, Kristi L.

    2010-04-02T23:59:59.000Z

    for their role in the negative regulation of canonical Wnt signaling. However, functions of APC in other important cellular processes, such as cell cycle control or aneuploidy, are only beginning to be studied. Our previous investigation implicated the 15-amino...

  12. The Hairpin Ribozyme Substrate Binding-domain: A Highly Constrained D-shaped Conformation

    E-Print Network [OSTI]

    Walter, Nils G.

    .g. NMR or X-ray crystallography, is their inability to dene exible regions. This problem is especially, 1998). There is no X-ray crystal or complete NMR structure for the hairpin ribozyme (Cai & Tinoco Jral Montreal, Quebec, H3C 3J7 Canada 3 Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA 4

  13. Crystal and Solution Structures of the Helicase-Binding Domain of Escherichia coli Primase

    E-Print Network [OSTI]

    Otting, Gottfried

    Otting and Nicholas E. Dixon SUPPLEMENTAL DATA Overproduction of DnaG(1­433), p49 Plasmid pPL195 (1 primer 10 was as described (2). The 2000-bp dnaG+ BamHI fragment was isolated from pPL195 and inserted-length DnaG primase, directed by plasmid pPL195 (1). BL21(DE3)recA/pPL195 cells were grown at 30 °C in LB

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

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

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative1 First Use of Energy for All Purposes (Fuel and Nonfuel), 2002; Level:Energy: Grid Integration Redefining What'sis Taking Over Our InstagramStructure of All-Polymer Solar Cells ImpedesStructure ofHuman Toll-like

  15. Multi-PAS domain-mediated protein oligomerization of PpsR from Rhodobacter sphaeroides

    SciTech Connect (OSTI)

    Heintz, Udo; Meinhart, Anton; Winkler, Andreas, E-mail: andreas.winkler@mpimf-heidelberg.mpg.de [Max Planck Institute for Medical Research, Heidelberg (Germany)

    2014-03-01T23:59:59.000Z

    Crystal structures of two truncated variants of the transcription factor PpsR from R. sphaeroides are presented that enabled the phasing of a triple PAS domain construct. Together, these structures reveal the importance of ?-helical PAS extensions for multi-PAS domain-mediated protein oligomerization and function. PerARNTSim (PAS) domains are essential modules of many multi-domain signalling proteins that mediate protein interaction and/or sense environmental stimuli. Frequently, multiple PAS domains are present within single polypeptide chains, where their interplay is required for protein function. Although many isolated PAS domain structures have been reported over the last decades, only a few structures of multi-PAS proteins are known. Therefore, the molecular mechanism of multi-PAS domain-mediated protein oligomerization and function is poorly understood. The transcription factor PpsR from Rhodobacter sphaeroides is such a multi-PAS domain protein that, in addition to its three PAS domains, contains a glutamine-rich linker and a C-terminal helixturnhelix DNA-binding motif. Here, crystal structures of two N-terminally and C-terminally truncated PpsR variants that comprise a single (PpsR{sub Q-PAS1}) and two (PpsR{sub N-Q-PAS1}) PAS domains, respectively, are presented and the multi-step strategy required for the phasing of a triple PAS domain construct (PpsR{sub ?HTH}) is illustrated. While parts of the biologically relevant dimerization interface can already be observed in the two shorter constructs, the PpsR{sub ?HTH} structure reveals how three PAS domains enable the formation of multiple oligomeric states (dimer, tetramer and octamer), highlighting that not only the PAS cores but also their ?-helical extensions are essential for protein oligomerization. The results demonstrate that the long helical glutamine-rich linker of PpsR results from a direct fusion of the N-cap of the PAS1 domain with the C-terminal extension of the N-domain that plays an important role in signal transduction.

  16. Crystal Structures of the Tetratricopeptide Repeat Domains of Kinesin Light Chains: Insight into Cargo Recognition Mechanisms

    SciTech Connect (OSTI)

    Zhu, Haizhong; Lee, Han Youl; Tong, Yufeng; Hong, Bum-Soo; Kim, Kyung-Phil; Shen, Yang; Lim, Kyung Jik; Mackenzie, Farrell; Tempel, Wolfram; Park, Hee-Won (SGC-Toronto); (PPCS); (Toronto)

    2012-10-23T23:59:59.000Z

    Kinesin-1 transports various cargos along the axon by interacting with the cargos through its light chain subunit. Kinesin light chains (KLC) utilize its tetratricopeptide repeat (TPR) domain to interact with over 10 different cargos. Despite a high sequence identity between their TPR domains (87%), KLC1 and KLC2 isoforms exhibit differential binding properties towards some cargos. We determined the structures of human KLC1 and KLC2 tetratricopeptide repeat (TPR) domains using X-ray crystallography and investigated the different mechanisms by which KLCs interact with their cargos. Using isothermal titration calorimetry, we attributed the specific interaction between KLC1 and JNK-interacting protein 1 (JIP1) cargo to residue N343 in the fourth TRP repeat. Structurally, the N343 residue is adjacent to other asparagines and lysines, creating a positively charged polar patch within the groove of the TPR domain. Whereas, KLC2 with the corresponding residue S328 did not interact with JIP1. Based on these finding, we propose that N343 of KLC1 can form 'a carboxylate clamp' with its neighboring asparagine to interact with JIP1, similar to that of HSP70/HSP90 organizing protein-1's (HOP1) interaction with heat shock proteins. For the binding of cargos shared by KLC1 and KLC2, we propose a different site located within the groove but not involving N343. We further propose a third binding site on KLC1 which involves a stretch of polar residues along the inter-TPR loops that may form a network of hydrogen bonds to JIP3 and JIP4. Together, these results provide structural insights into possible mechanisms of interaction between KLC TPR domains and various cargo proteins.

  17. Probing the Impact of the EchinT C-Terminal Domain on Structure and Catalysis

    SciTech Connect (OSTI)

    S Bardaweel; J Pace; T Chou; V Cody; C Wagner

    2011-12-31T23:59:59.000Z

    Histidine triad nucleotide binding protein (Hint) is considered as the ancestor of the histidine triad protein superfamily and is highly conserved from bacteria to humans. Prokaryote genomes, including a wide array of both Gram-negative bacteria and Gram-positive bacteria, typically encode one Hint gene. The cellular function of Hint and the rationale for its evolutionary conservation in bacteria have remained a mystery. Despite its ubiquity and high sequence similarity to eukaryote Hint1 [Escherichia coli Hint (echinT) is 48% identical with human Hint1], prokaryote Hint has been reported in only a few studies. Here we report the first conformational information on the full-length N-terminal and C-terminal residues of Hint from the E. coli complex with GMP. Structural analysis of the echinT-GMP complex reveals that it crystallizes in the monoclinic space group P2{sub 1} with four homodimers in the asymmetric unit. Analysis of electron density for both the N-terminal residues and the C-terminal residues of the echinT-GMP complex indicates that the loops in some monomers can adopt more than one conformation. The observation of conformational flexibility in terminal loop regions could explain the presence of multiple homodimers in the asymmetric unit of this structure. To explore the impact of the echinT C-terminus on protein structure and catalysis, we conducted a series of catalytic radiolabeling and kinetic experiments on the C-terminal deletion mutants of echinT. In this study, we show that sequential deletion of the C-terminus likely has no effect on homodimerization and a modest effect on the secondary structure of echinT. However, we observed a significant impact on the folding structure, as reflected by a significant lowering of the T{sub m} value. Kinetic analysis reveals that the C-terminal deletion mutants are within an order of magnitude less efficient in catalysis compared to wild type, while the overall kinetic mechanism that proceeds through a fast step, followed by a rate-limiting hydrolysis step, was conserved. Nevertheless, the ability of the C-terminal deletion mutants to hydrolyze lysyl-AMP generated by LysU was greatly impaired. Taken together, our results highlight the emerging role of the C-terminus in governing the catalytic function of Hints.

  18. Performance Assessment Report Domain CHP System

    E-Print Network [OSTI]

    Oak Ridge National Laboratory

    Performance Assessment Report for the Domain CHP System November 2005 By Burns & McDonnell Engineering #12;Domain CHP System Performance Assessment Report for the Packaged Cooling, Heating and Power

  19. Magnetic domain walls driven by interfacial phenomena

    E-Print Network [OSTI]

    Emori, Satoru

    2014-01-01T23:59:59.000Z

    A domain wall in a ferromagnetic material is a boundary between differently magnetized regions, and its motion provides a convenient scheme to control the magnetization state of the material. Domain walls can be confined ...

  20. DOMAIN DECOMPOSITION FOR A MIXED FINITE ELEMENT ...

    E-Print Network [OSTI]

    SIAM (#1) 1035 2001 Apr 10 12:32:38

    2003-03-12T23:59:59.000Z

    ... porous media, where highly discontinuous conductivity coefficients are also ...... [14] B. Smith, P. Bjrstad, and W. Gropp, Domain Decomposition, Cambridge

  1. Effective Supergravity for Supergravity Domain Walls

    E-Print Network [OSTI]

    M. Cvetic; N. D. Lambert

    2002-05-23T23:59:59.000Z

    We discuss the low energy effective action for the Bosonic and Fermionic zero-modes of a smooth BPS Randall-Sundrum domain wall, including the induced supergravity on the wall. The result is a pure supergravity in one lower dimension. In particular, and in contrast to non-gravitational domain walls or domain walls in a compact space, the zero-modes representing transverse fluctuations of domain wall have vanishing action.

  2. Magnetic domains were not found in tetrataenite.

    E-Print Network [OSTI]

    Mountziaris, T. J.

    collaboration with electrical engineers to produce the proper magnetic tape to view domains in. Observing and Industrial Engineering, University of Massachusetts, Amherst, MA 01003 Future Work While the magnetism Magnetic domains were not found in tetrataenite. Figure 4 shows magnetic domains found

  3. Concrete Domains and Nominals United Carlos Areces

    E-Print Network [OSTI]

    Lutz, Carsten

    Concrete Domains and Nominals United Carlos Areces University of Amsterdam The Netherlands carlos(D), the extension of ALC with concrete domains, is known to be PSpace-complete, in this article we show on the concrete domain D used). The proof is by a reduction of a NExpTime-complete variant of the domino problem

  4. Labelling Heuristics for CSP Application Domains

    E-Print Network [OSTI]

    Rossi, Francesca

    Labelling Heuristics for CSP Application Domains Zeynep K#16;z#16;ltan Computer Science Division an application domain as a family of CSP models, so as to exhibit the generic constraint store for all models store and the domain propagation during search is analysed, so as to infer | before modelling any CSP

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

    Office of Environmental Management (EM)

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

  6. Word Domain Disambiguation via Word Sense Disambiguation

    SciTech Connect (OSTI)

    Sanfilippo, Antonio P.; Tratz, Stephen C.; Gregory, Michelle L.

    2006-06-04T23:59:59.000Z

    Word subject domains have been widely used to improve the perform-ance of word sense disambiguation al-gorithms. However, comparatively little effort has been devoted so far to the disambiguation of word subject do-mains. The few existing approaches have focused on the development of al-gorithms specific to word domain dis-ambiguation. In this paper we explore an alternative approach where word domain disambiguation is achieved via word sense disambiguation. Our study shows that this approach yields very strong results, suggesting that word domain disambiguation can be ad-dressed in terms of word sense disam-biguation with no need for special purpose algorithms.

  7. Chromosome 12p Deletions in TEL-AML1 Childhood Acute Lymphoblastic Leukemia Are Associated with Retrotransposon

    E-Print Network [OSTI]

    California at Berkeley, University of

    Chromosome 12p Deletions in TEL-AML1 Childhood Acute Lymphoblastic Leukemia Are Associated Acute lymphoblastic leukemia is the most common diagnosis in childhood cancer; and f22% of children, Rhode Island Abstract TEL-AML1 (ETV6-RUNX1) is the most common translocation in the childhood leukemias

  8. Structures and solution properties of two novel periplasmic sensor domains with c-type heme from chemotaxis proteins of Geobacter sulfurreducens : implications for signal transduction.

    SciTech Connect (OSTI)

    Pokkuluri, P. R.; Pessanha, M.; Londer, Y. Y.; Wood, S. J.; Duke, N. E. C.; Wilton, R.; Catarino, T.; Salgueiro, C. A.; Schiffer, M.; Biosciences Division; Univ.Nova de Lisboa; Insti. de Tecnologia Quimica e Biologica

    2008-04-11T23:59:59.000Z

    Periplasmic sensor domains from two methyl-accepting chemotaxis proteins from Geobacter sulfurreducens (encoded by genes GSU0935 and GSU0582) were expressed in Escherichia coli. The sensor domains were isolated, purified, characterized in solution, and their crystal structures were determined. In the crystal, both sensor domains form swapped dimers and show a PAS-type fold. The swapped segment consists of two helices of about 45 residues at the N terminus with the hemes located between the two monomers. In the case of the GSU0582 sensor, the dimer contains a crystallographic 2-fold symmetry and the heme is coordinated by an axial His and a water molecule. In the case of the GSU0935 sensor, the crystals contain a non-crystallographic dimer, and surprisingly, the coordination of the heme in each monomer is different; monomer A heme has His-Met ligation and monomer B heme has His-water ligation as found in the GSU0582 sensor. The structures of these sensor domains are the first structures of PAS domains containing covalently bound heme. Optical absorption, electron paramagnetic resonance and NMR spectroscopy have revealed that the heme groups of both sensor domains are high-spin and low-spin in the oxidized and reduced forms, respectively, and that the spin-state interconversion involves a heme axial ligand replacement. Both sensor domains bind NO in their ferric and ferrous forms but bind CO only in the reduced form. The binding of both NO and CO occurs via an axial ligand exchange process, and is fully reversible. The reduction potentials of the sensor domains differ by 95 mV (-156 mV and -251 mV for sensors GSU0582 and GSU0935, respectively). The swapped dimerization of these sensor domains and redox-linked ligand switch might be related to the mechanism of signal transduction by these chemotaxis proteins.

  9. Biological activities of binding site specific monoclonal antibodies to prolactin receptors of rabbit mammary gland

    SciTech Connect (OSTI)

    Djiane, J.; Dusanter-Fourt, I.; Katoh, M.; Kelly, P.A.

    1985-09-25T23:59:59.000Z

    The biological activity of three monoclonal antibodies (mAbs) against the rabbit mammary prolactin (PRL) receptor (M110, A82, and A917) were investigated using explants of rabbit mammary gland. The three mAbs which were all able to inhibit the binding of SVI-ovine prolactin to its receptor had different biological activities. Two mAbs (M110 and A82) were able to prevent the stimulating effect of PRL on casein synthesis when the molar ratio between the mAb and PRL was 100. One mAb (A917) was able to mimic the action of PRL on both casein and DNA ((TH)thymidine incorporation) synthesis, whereas the other two mAbs were without any stimulatory effect. For this stimulatory effect to be observed, bivalency of the antibody was essential, since monovalent fragments, which were able to inhibit PRL binding, had no agonistic activity. The ability of the mAbs to induce a down-regulation of receptors was also studied. These studies suggest that the binding domain of the receptor might be relatively complex, since only a part of this domain recognized by the antibody with PRL-like activity was able to induce hormonal action. Alternatively, only those antibodies able to microaggregate the receptors may possess PRL-like activity.

  10. Dissipation, noise and DCC domain formation

    E-Print Network [OSTI]

    A. K. Chaudhuri

    1999-08-17T23:59:59.000Z

    We investigate the effect of friction on domain formation in disoriented chiral condensate. We solve the equation of motion of the linear sigma model, in the Hartree approximation, including a friction and a white noise term. For quenched initial condition, we find that even in presence of noise and dissipation domain like structure emerges after a few fermi of evolution. Domain size as large as 5 fm can be formed.

  11. Unfurling of the band 4.1, ezrin, radixin, moesin (FERM) domain of the merlin tumor suppressor

    SciTech Connect (OSTI)

    Yogesha, S.D.; Sharff, Andrew J.; Giovannini, Marco; Bricogne, Gerard; Izard, Tina (House Ear); (Globel Phasing); (Scripps)

    2014-10-02T23:59:59.000Z

    The merlin-1 tumor suppressor is encoded by the Neurofibromatosis-2 (Nf2) gene and loss-of-function Nf2 mutations lead to nervous system tumors in man and to several tumor types in mice. Merlin is an ERM (ezrin, radixin, moesin) family cytoskeletal protein that interacts with other ERM proteins and with components of cell-cell adherens junctions (AJs). Merlin stabilizes the links of AJs to the actin cytoskeleton. Thus, its loss destabilizes AJs, promoting cell migration and invasion, which in Nf2{sup +/-} mice leads to highly metastatic tumors. Paradoxically, the 'closed' conformation of merlin-1, where its N-terminal four-point-one, ezrin, radixin, moesin (FERM) domain binds to its C-terminal tail domain, directs its tumor suppressor functions. Here we report the crystal structure of the human merlin-1 head domain when crystallized in the presence of its tail domain. Remarkably, unlike other ERM head-tail interactions, this structure suggests that binding of the tail provokes dimerization and dynamic movement and unfurling of the F2 motif of the FERM domain. We conclude the 'closed' tumor suppressor conformer of merlin-1 is in fact an 'open' dimer whose functions are disabled by Nf2 mutations that disrupt this architecture.

  12. Localized domain patterns in complex polymers

    E-Print Network [OSTI]

    Localized domain patterns in complex polymers abstract. Block copolymers are macromolecules that can form variety of microstructures as a result of incomplete

  13. Petroleum Pipeline Eminent Domain Permit Procedures (Georgia)

    Broader source: Energy.gov [DOE]

    The Petroleum Pipeline Eminent Domain Permit Procedures serve to protect Georgia's natural and environmental resources by requiring permits be issued by the Director of the Environmental Protection...

  14. 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...

  15. Function of the ATR N-terminal domain revealed by an ATM/ATR chimera

    SciTech Connect (OSTI)

    Chen Xinping [Department of Biochemistry, Vanderbilt University, 613 Light Hall, 23rd, Pierce Avenue, Nashville, TN 37232 (United States); Zhao Runxiang [Department of Biochemistry, Vanderbilt University, 613 Light Hall, 23rd, Pierce Avenue, Nashville, TN 37232 (United States); Glick, Gloria G. [Department of Biochemistry, Vanderbilt University, 613 Light Hall, 23rd, Pierce Avenue, Nashville, TN 37232 (United States); Cortez, David [Department of Biochemistry, Vanderbilt University, 613 Light Hall, 23rd, Pierce Avenue, Nashville, TN 37232 (United States)]. E-mail: david.cortez@vanderbilt.edu

    2007-05-01T23:59:59.000Z

    The ATM and ATR kinases function at the apex of checkpoint signaling pathways. These kinases share significant sequence similarity, phosphorylate many of the same substrates, and have overlapping roles in initiating cell cycle checkpoints. However, they sense DNA damage through distinct mechanisms. ATR primarily senses single stranded DNA (ssDNA) through its interaction with ATRIP, and ATM senses double strand breaks through its interaction with Nbs1. We determined that the N-terminus of ATR contains a domain that binds ATRIP. Attaching this domain to ATM allowed the fusion protein (ATM*) to bind ATRIP and associate with RPA-coated ssDNA. ATM* also gained the ability to localize efficiently to stalled replication forks as well as double strand breaks. Despite having normal kinase activity when tested in vitro and being phosphorylated on S1981 in vivo, ATM* is defective in checkpoint signaling and does not complement cellular deficiencies in either ATM or ATR. These data indicate that the N-terminus of ATR is sufficient to bind ATRIP and to promote localization to sites of replication stress.

  16. Crystallographic controls on uranyl binding at the quartz/water...

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

    controls on uranyl binding at the quartzwater interface. Abstract: Molecular dynamics methods were used to simulate UO2(OH)20 binding to pairs of oxo sites on three...

  17. Single-Molecule Dynamics Reveals Cooperative Binding-Folding...

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

    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...

  18. Atomic structure of nitrate-binding protein crucial for photosynthetic...

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

    structure of nitrate-binding protein crucial for photosynthetic productivity. Atomic structure of nitrate-binding protein crucial for photosynthetic productivity. Abstract:...

  19. affinity binding studies: Topics by E-print Network

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

    for Ligand Binding Affinity Prediction Chemistry Websites Summary: of the binding free energy between a ligand and a protein is an important component in the virtual...

  20. 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...

  1. Effects of Deletions of High Molecular Weight Glutenin Subunit Alleles on Dough Properties and Wheat Flour Tortilla Quality

    E-Print Network [OSTI]

    Tuncil, Yunus

    2012-10-19T23:59:59.000Z

    , Lloyd W. Rooney Dirk B. Hays Intercollegiate Faculty Chair, Alejandro Castillo August 2012 Major Subject: Food Science and Technology iii ABSTRACT Effects of Deletions of High Molecular Weight Glutenin Subunit Alleles on Dough... and opportunities he provided me. I am thankful to my committee members Dr. Lloyd Rooney for his encouragements and Dr. Dirk Hays providing directions. I acknowledge to Dr. Amir Ibrahim for his support and help with statistical analysis and interpretation. I...

  2. Deletion of exon 3 of the insulin receptor gene in a kindred with a familial form of insulin resistance

    SciTech Connect (OSTI)

    Wertheimer, E.; Barbetti, F.; Accili, D.; Taylor, S.I. [National Institutes of Health, Bethesda, MD (United States)] [National Institutes of Health, Bethesda, MD (United States); Litvin, Y.; Ebstein, R.P.; Bennet, E.R.

    1994-05-01T23:59:59.000Z

    Molecular scanning techniques, such as denaturing gradient gel electrophoresis (DGGE), greatly facilitate screening candidate genes for mutations. The authors have used DGGE to screen for mutations in the insulin receptor gene in a family in which four of five daughters were affected by type A insulin resistance in association with acanthosis nigricans and hyperandrogenism. DGGE did not detect mutations in any of the 22 exons of the insulin receptor gene. Nevertheless, Southern blot analysis suggested that there was a deletion of exon 3 in the other paternal allele of the insulin receptor gene. Analysis of the father`s cDNA confirmed that exon 3 was deleted from mRNA molecules derived from one of his two alleles of the insulin receptor gene. Furthermore, the father was found to be hemizygous for a polymorphic sequence (GAC{sup Asp} at codon 234) in exon 3 that was not inherited by any of the five daughters. Instead, all five daughters inherited the paternal allele with the deletion mutation. They did not detect mutations in the mother`s insulin receptor gene. Furthermore, the clinical syndrome did not segregate with either of the mother`s two alleles of the insulin receptor gene. Although the youngest daughter inherited the mutant allele from her father, she was not clinically affected. The explanation for the incomplete penetrance is not known. These results emphasize the importance of specifically searching for deletion mutations when screening candidate genes for mutations. Furthermore, the existence of apparently asymptomatic carriers of mutations in the insulin receptor gene, such as the father in the present study, suggests that the prevalence of mutations in the insulin receptor gene may be higher than would be predicted on the basis of the observed prevalence of patients with extreme insulin resistance. 34 refs., 6 figs., 1 tab.

  3. DefectDomain Wall Interactions in Trigonal

    E-Print Network [OSTI]

    Gopalan, Venkatraman

    DefectDomain Wall Interactions in Trigonal Ferroelectrics Venkatraman Gopalan,1 Volkmar Dierolf,2 walls in the trigonal ferroelectrics lithium niobate and lithium tantalate. It is shown that extrinsic questions re- garding intrinsic widths, defectdomain wall interactions, and static versus dynamic wall

  4. A Theoretical Framework for Chimera Domain Decomposition

    E-Print Network [OSTI]

    Keeling, Stephen L.

    A Theoretical Framework for Chimera Domain Decomposition S. L. Keeling Sverdrup Technology, Inc. Steger, UC Davis, May 2-4, 1997. 1 Introduction. The Chimera scheme is a domain decomposition method- ometry is divided into simply shaped regions. Unlike other approaches [5], the Chimera method simplifies

  5. Reasoning with Concrete Domains Carsten Lutz

    E-Print Network [OSTI]

    Lutz, Carsten

    Reasoning with Concrete Domains Carsten Lutz RWTH Aachen, LuFg Theoretical Computer Science. Concrete domains allow the integration of description logic reasoning with reasoning about concrete objects for building real­world applications, is widely accepted. How­ ever, the complexity of reasoning with concrete

  6. Unexpected effects of gene deletion on mercury interactions with the methylation-deficient mutant hgcAB

    SciTech Connect (OSTI)

    Lin, Hui [ORNL] [ORNL; Hurt, Jr., Richard Ashley [ORNL; Johs, Alexander [ORNL] [ORNL; Parks, Jerry M [ORNL] [ORNL; Morrell-Falvey, Jennifer L [ORNL] [ORNL; Liang, Liyuan [ORNL] [ORNL; Elias, Dwayne A [ORNL] [ORNL; Gu, Baohua [ORNL] [ORNL

    2014-01-01T23:59:59.000Z

    The hgcA and hgcB gene pair is essential for mercury (Hg) methylation by certain anaerobic bacteria,1 but little is known about how deletion of hgcAB affects cell surface interactions and intracellular uptake of Hg. Here, we compare hgcAB mutants with the wild-type (WT) strains of both Geobacter sulfurreducens PCA and Desulfovibrio desulfuricans ND132 and observe differences in Hg redox transformations, adsorption, and uptake in laboratory incubation studies. In both strains, deletion of hgcAB increased the reduction of Hg(II) but decreased the oxidation of Hg(0) under anaerobic conditions. The measured cellular thiol content in hgcAB mutants was lower than the WT, accounting for decreased adsorption and uptake of Hg. Despite the lack of methylation activity, Hg uptake by the hgcAB continued, albeit at a slower rate than the WT. These findings demonstrate that deletion of the hgcAB gene not only eliminates Hg methylation but also alters cell physiology, resulting in changes to Hg redox reactions, sorption, and uptake by cells.

  7. Hardware device binding and mutual authentication

    DOE Patents [OSTI]

    Hamlet, Jason R; Pierson, Lyndon G

    2014-03-04T23:59:59.000Z

    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.

  8. Identification of a Unique Ganglioside Binding Loop within Botulinum Neurotoxins C and D-SA

    SciTech Connect (OSTI)

    Karalewitz, Andrew P.-A.; Kroken, Abby R.; Fu, Zhuji; Baldwin, Michael R.; Kim, Jung-Ja P.; Barbieri, Joseph T. (MCW); (Missouri)

    2010-09-22T23:59:59.000Z

    The botulinum neurotoxins (BoNTs) are the most potent protein toxins for humans. There are seven serotypes of BoNTs (A-G) based on a lack of cross antiserum neutralization. BoNTs utilize gangliosides as components of the host receptors for binding and entry into neurons. Members of BoNT/C and BoNT/D serotypes include mosaic toxins that are organized in D/C and C/D toxins. One D/C mosaic toxin, BoNT/D-South Africa (BoNT/D-SA), was not fully neutralized by immunization with BoNT serotype C or D, which stimulated this study. Here the crystal structures of the receptor binding domains of BoNT/C, BoNT/D, and BoNT/D-SA are presented. Biochemical and cell binding studies show that BoNT/C and BoNT/D-SA possess unique mechanisms for ganglioside binding. These studies provide new information about how the BoNTs can enter host cells as well as a basis for understanding the immunological diversity of these neurotoxins.

  9. Optical coherence domain reflectometry guidewire

    DOE Patents [OSTI]

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

    2001-01-01T23:59:59.000Z

    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.

  10. Bridging the gap between protein-tyrosine phosphorylation networks, metabolism and physiology in liver-specific PTP1b deletion mice

    E-Print Network [OSTI]

    Miraldi, Emily R. (Emily Rae)

    2012-01-01T23:59:59.000Z

    Metabolic syndrome describes a complex set of obesity-related disorders that enhance diabetes, cardiovascular, and mortality risk. Studies of liver-specific protein-tyrosine phosphatase lb (PTPlb) deletion mice (L-PTPlb-/-) ...

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

    DOE Patents [OSTI]

    Mayfield, Stephen P.

    2006-10-17T23:59:59.000Z

    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.

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

    DOE Patents [OSTI]

    Mayfield, Stephen (Cardiff, CA)

    2000-01-01T23:59:59.000Z

    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.

  13. Postinduction represssion of the. beta. -interferon gene is mediated through two positive regulatory domains

    SciTech Connect (OSTI)

    Whittemore, L.A.; Maniatis, T. (Harvard Univ., Cambridge, MA (USA))

    1990-10-01T23:59:59.000Z

    Virus induction of the human {beta}-interferon ({beta}-IFN) gene results in an increase in the rate of {beta}-IFN mRNA synthesis, followed by a rapid postinduction decrease. In this paper, the authors show that two {beta}-IFN promoter elements, positive regulatory domains I and II (PRDI and PRDII), which are required for virus induction of the {beta}-IFN gene are also required for the postinduction turnoff. Although protein synthesis is not necessary for activation, it is necessary for repression of these promoter elements. Examination of nuclear extracts from cells infected with virus reveals the presence of virus-inducible, cycloheximide-sensitive, DNA-binding activities that interact specifically with PRDI or PRDII. They propose that the postinduction repression of {beta}-IFN gene transcription involves virus inducible repressors that either bind directly to the positive regulatory elements of the {beta}-IFN promoter or inactivate the positive regulatory factors bound to PRDI and PRDII.

  14. The human ACC2 CT-domain C-terminus is required for full functionality and has a novel twist

    SciTech Connect (OSTI)

    Madauss, Kevin P.; Burkhart, William A.; Consler, Thomas G.; Cowan, David J.; Gottschalk, William K.; Miller, Aaron B; Short, Steven A.; Tran, Thuy B.; Williams, Shawn P.; (GSKNC); (Duke); (UNC)

    2009-06-15T23:59:59.000Z

    Inhibition of acetyl-CoA carboxylase (ACC) may prevent lipid-induced insulin resistance and type 2 diabetes, making the enzyme an attractive pharmaceutical target. Although the enzyme is highly conserved amongst animals, only the yeast enzyme structure is available for rational drug design. The use of biophysical assays has permitted the identification of a specific C-terminal truncation of the 826-residue human ACC2 carboxyl transferase (CT) domain that is both functionally competent to bind inhibitors and crystallizes in their presence. This C-terminal truncation led to the determination of the human ACC2 CT domain-CP-640186 complex crystal structure, which revealed distinctions from the yeast-enzyme complex. The human ACC2 CT-domain C-terminus is comprised of three intertwined -helices that extend outwards from the enzyme on the opposite side to the ligand-binding site. Differences in the observed inhibitor conformation between the yeast and human structures are caused by differing residues in the binding pocket.

  15. 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. (MIT); (UT-Australia); (Macquarie); (Toronto); (New South)

    2012-02-15T23:59:59.000Z

    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.

  16. Structure of a NEMO/IKK-Associating Domain Reveals Architecture of the Interaction Site

    SciTech Connect (OSTI)

    Rushe,M.; Silvian, L.; Bixler, S.; Chen, L.; Cheung, A.; Bowes, S.; Cuervo, H.; Berkowitz, S.; Zheng, T.; et al

    2008-01-01T23:59:59.000Z

    The phosphorylation of I{kappa}B by the IKK complex targets it for degradation and releases NF-{kappa}B for translocation into the nucleus to initiate the inflammatory response, cell proliferation, or cell differentiation. The IKK complex is composed of the catalytic IKK{alpha}/{beta} kinases and a regulatory protein, NF-{kappa}B essential modulator (NEMO; IKK{gamma}). NEMO associates with the unphosphorylated IKK kinase C termini and activates the IKK complex's catalytic activity. However, detailed structural information about the NEMO/IKK interaction is lacking. In this study, we have identified the minimal requirements for NEMO and IKK kinase association using a variety of biophysical techniques and have solved two crystal structures of the minimal NEMO/IKK kinase associating domains. We demonstrate that the NEMO core domain is a dimer that binds two IKK fragments and identify energetic hot spots that can be exploited to inhibit IKK complex formation with a therapeutic agent.

  17. Localized Domains of Disoriented Chiral Condensates

    E-Print Network [OSTI]

    B. K. Nandi; T. K. Nayak; B. Mohanty; D. P. Mahapatra; Y. P. Viyogi

    1999-03-12T23:59:59.000Z

    A new method to search for localized domains of disoriented chiral condensates (DCC) has been proposed by utilising the (eta-phi) phase space distributions of charged particles and photons. Using the discrete wavelet transformation (DWT) analysis technique, it has been found that the presence of DCC domains broadens the distribution of wavelet coefficients in comparison to that of normal events. Strength contours have been derived from the differences in rms deviations of these distributions by taking into account the size of DCC domains and the probability of DCC production in ultra-relativistic heavy ion collisions. This technique can be suitably adopted to experiments measuring multiplicities of charged particles and photons.

  18. Domain wall cosmology and multiple accelerations

    SciTech Connect (OSTI)

    Lee, Bum-Hoon [CQUeST, Sogang University, Seoul, Korea 121-742 (Korea, Republic of); Department of Physics, Sogang University, Seoul, 121-742 (Korea, Republic of); Lee, Wonwoo; Nam, Siyoung; Park, Chanyong [CQUeST, Sogang University, Seoul, 121-742 (Korea, Republic of)

    2007-05-15T23:59:59.000Z

    We classify the cosmological behaviors of the domain wall under junctions between two spacetimes in terms of various parameters: cosmological constants of bulk spacetime, a tension of a domain wall, and mass parameters of the black-hole-type metric. Especially, we consider the false-true vacuum-type junctions and the domain wall connecting between an inner AdS space and an outer AdS Reissner-Nordstroem black hole. We find that there exists a solution to the junction equations with multiple accelerations.

  19. The structure of the PERK kinase domain suggests the mechanism for its activation

    SciTech Connect (OSTI)

    Cui, Wenjun; Li, Jingzhi; Ron, David; Sha, Bingdong (UAB); (Cambridge)

    2012-08-31T23:59:59.000Z

    The endoplasmic reticulum (ER) unfolded protein response (UPR) is comprised of several intracellular signaling pathways that alleviate ER stress. The ER-localized transmembrane kinase PERK is one of three major ER stress transducers. Oligomerization of PERK's N-terminal ER luminal domain by ER stress promotes PERK trans-autophosphorylation of the C-terminal cytoplasmic kinase domain at multiple residues including Thr980 on the kinase activation loop. Activated PERK phosphorylates Ser51 of the {alpha}-subunit of translation initiation factor 2 (eIF2{alpha}), which inhibits initiation of protein synthesis and reduces the load of unfolded proteins entering the ER. The crystal structure of PERK's kinase domain has been determined to 2.8 {angstrom} resolution. The structure resembles the back-to-back dimer observed in the related eIF2{alpha} kinase PKR. Phosphorylation of Thr980 stabilizes both the activation loop and helix {alpha}G in the C-terminal lobe, preparing the latter for eIF2{alpha} binding. The structure suggests conservation in the mode of activation of eIF2{alpha} kinases and is consistent with a 'line-up' model for PERK activation triggered by oligomerization of its luminal domain.

  20. Crystal Structure and Functional Interpretation of the Erythrocyte spectrin Tetramerization Domain Complex

    SciTech Connect (OSTI)

    J Ipsaro; S Harper; T Messick; R Marmorstein; A Mondragon; D Speicher

    2011-12-31T23:59:59.000Z

    As the principal component of the membrane skeleton, spectrin confers integrity and flexibility to red cell membranes. Although this network involves many interactions, the most common hemolytic anemia mutations that disrupt erythrocyte morphology affect the spectrin tetramerization domains. Although much is known clinically about the resulting conditions (hereditary elliptocytosis and pyropoikilocytosis), the detailed structural basis for spectrin tetramerization and its disruption by hereditary anemia mutations remains elusive. Thus, to provide further insights into spectrin assembly and tetramer site mutations, a crystal structure of the spectrin tetramerization domain complex has been determined. Architecturally, this complex shows striking resemblance to multirepeat spectrin fragments, with the interacting tetramer site region forming a central, composite repeat. This structure identifies conformational changes in {alpha}-spectrin that occur upon binding to {beta}-spectrin, and it reports the first structure of the {beta}-spectrin tetramerization domain. Analysis of the interaction surfaces indicates an extensive interface dominated by hydrophobic contacts and supplemented by electrostatic complementarity. Analysis of evolutionarily conserved residues suggests additional surfaces that may form important interactions. Finally, mapping of hereditary anemia-related mutations onto the structure demonstrate that most, but not all, local hereditary anemia mutations map to the interacting domains. The potential molecular effects of these mutations are described.

  1. Crystal structure and functional interpretation of the erythrocyte spectrin tetramerization domain complex

    SciTech Connect (OSTI)

    Ipsaro, Jonathan J.; Harper, Sandra L.; Messick, Troy E.; Marmorstein, Ronen; Mondragn, Alfonso; Speicher, David W. (Wistar); (NWU)

    2010-09-07T23:59:59.000Z

    As the principal component of the membrane skeleton, spectrin confers integrity and flexibility to red cell membranes. Although this network involves many interactions, the most common hemolytic anemia mutations that disrupt erythrocyte morphology affect the spectrin tetramerization domains. Although much is known clinically about the resulting conditions (hereditary elliptocytosis and pyropoikilocytosis), the detailed structural basis for spectrin tetramerization and its disruption by hereditary anemia mutations remains elusive. Thus, to provide further insights into spectrin assembly and tetramer site mutations, a crystal structure of the spectrin tetramerization domain complex has been determined. Architecturally, this complex shows striking resemblance to multirepeat spectrin fragments, with the interacting tetramer site region forming a central, composite repeat. This structure identifies conformational changes in {alpha}-spectrin that occur upon binding to {beta}-spectrin, and it reports the first structure of the {beta}-spectrin tetramerization domain. Analysis of the interaction surfaces indicates an extensive interface dominated by hydrophobic contacts and supplemented by electrostatic complementarity. Analysis of evolutionarily conserved residues suggests additional surfaces that may form important interactions. Finally, mapping of hereditary anemia-related mutations onto the structure demonstrate that most, but not all, local hereditary anemia mutations map to the interacting domains. The potential molecular effects of these mutations are described.

  2. Human-computer interface incorporating personal and application domains

    DOE Patents [OSTI]

    Anderson, Thomas G. (Albuquerque, NM)

    2011-03-29T23:59:59.000Z

    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.

  3. Learning Energy Demand Domain Knowledge via Feature Transformation

    E-Print Network [OSTI]

    Povinelli, Richard J.

    Learning Energy Demand Domain Knowledge via Feature Transformation Sanzad Siddique Department -- Domain knowledge is an essential factor for forecasting energy demand. This paper introduces a method knowledge substantially improves energy demand forecasting accuracy. However, domain knowledge may differ

  4. Structural and Functional Characterization of DUF1471 Domains...

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

    subfamilies: SrfN, YahO, and SssBYdgH (two of its three DUF1471 domains: the N-terminal domain I (residues 2191), and the C-terminal domain III (residues...

  5. PRL-1 Protein Promotes ERK1/2 and RhoA Protein Activation through a Non-canonical Interaction with the Src Homology 3 Domain of p115 Rho GTPase-activating Protein

    SciTech Connect (OSTI)

    Bai, Yunpeng; Luo, Yong; Liu, Sijiu; Zhang, Lujuan; Shen, Kui; Dong, Yuanshu; Walls, Chad D.; Quilliam, Lawrence A.; Wells, Clark D.; Cao, Youjia; Zhang, Zhong-Yin (Indiana-Med); (NIU); (Nankai)

    2012-03-15T23:59:59.000Z

    Phosphatases of the regenerating liver (PRL) play oncogenic roles in cancer development and metastasis. Although previous studies indicate that PRL-1 promotes cell growth and migration by activating both the ERK1/2 and RhoA pathways, the mechanism by which it activates these signaling events remains unclear. We have identified a PRL-1-binding peptide (Peptide 1) that shares high sequence identity with a conserved motif in the Src homology 3 (SH3) domain of p115 Rho GTPase-activating protein (GAP). p115 RhoGAP directly binds PRL-1 in vitro and in cells via its SH3 domain. Structural analyses of the PRL-1 {center_dot} Peptide 1 complex revealed a novel protein-protein interaction whereby a sequence motif within the PxxP ligand-binding site of the p115 RhoGAP SH3 domain occupies a folded groove within PRL-1. This prevents the canonical interaction between the SH3 domain of p115 RhoGAP and MEKK1 and results in activation of ERK1/2. Furthermore, PRL-1 binding activates RhoA signaling by inhibiting the catalytic activity of p115 RhoGAP. The results demonstrate that PRL-1 binding to p115 RhoGAP provides a coordinated mechanism underlying ERK1/2 and RhoA activation.

  6. Asymptotically radial solutions in expanding annular domains

    E-Print Network [OSTI]

    Clapp, Mnica

    Asymptotically radial solutions in expanding annular domains Thomas Bartsch Monica Clapp Massimo- mail: Thomas.Bartsch@math.uni-giessen.de Instituto de Matematicas, Universidad Nacional Autonoma de M

  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...

  8. Wavelet Domain Based Techniques for Video Coding

    E-Print Network [OSTI]

    Kutil, Rade

    Wavelet Domain Based Techniques for Video Coding Dissertation zur Erlangung des Doktorgrades an der . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 2.4.3 Error Resilience . . . . . . . . . . . . . . . . . . . . . . . . 17 3 Wavelet Transform 18 3.1 Wavelet Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 3.1.1 Fourier Transform (FT

  9. Casimir forces in the time domain: Applications

    E-Print Network [OSTI]

    Johnson, Steven G.

    Our previous article [Phys. Rev. A 80, 012115 (2009)] introduced a method to compute Casimir forces in arbitrary geometries and for arbitrary materials that was based on a finite-difference time-domain (FDTD) scheme. In ...

  10. Activation of p115-RhoGEF Requires Direct Association of G[alpha subscript 13] and the Dbl Homology Domain

    SciTech Connect (OSTI)

    Chen, Zhe; Guo, Liang; Hadas, Jana; Gutowski, Stephen; Sprang, Stephen R.; Sternweis, Paul C. (IIT); (UTSMC); (Montana)

    2012-09-05T23:59:59.000Z

    RGS-containing RhoGEFs (RGS-RhoGEFs) represent a direct link between the G{sub 12} class of heterotrimeric G proteins and the monomeric GTPases. In addition to the canonical Dbl homology (DH) and pleckstrin homology domains that carry out the guanine nucleotide exchange factor (GEF) activity toward RhoA, these RhoGEFs also possess RGS homology (RH) domains that interact with activated {alpha} subunits of G{sub 12} and G{sub 13}. Although the GEF activity of p115-RhoGEF (p115), an RGS-RhoGEF, can be stimulated by G{alpha}{sub 13}, the exact mechanism of the stimulation has remained unclear. Using combined studies with small angle x-ray scattering, biochemistry, and mutagenesis, we identify an additional binding site for activated G{alpha}{sub 13} in the DH domain of p115. Small angle x-ray scattering reveals that the helical domain of G{alpha}{sub 13} docks onto the DH domain, opposite to the surface of DH that binds RhoA. Mutation of a single tryptophan residue in the {alpha}3b helix of DH reduces binding to activated G{alpha}{sub 13} and ablates the stimulation of p115 by G{alpha}{sub 13}. Complementary mutations at the predicted DH-binding site in the {alpha}B-{alpha}C loop of the helical domain of G{alpha}{sub 13} also affect stimulation of p115 by G{alpha}{sub 13}. Although the GAP activity of p115 is not required for stimulation by G{alpha}{sub 13}, two hydrophobic motifs in RH outside of the consensus RGS box are critical for this process. Therefore, the binding of G{alpha}{sub 13} to the RH domain facilitates direct association of G{alpha}{sub 13} to the DH domain to regulate its exchange activity. This study provides new insight into the mechanism of regulation of the RGS-RhoGEF and broadens our understanding of G protein signaling.

  11. Structural basis of substrate discrimination and integrin binding by autotaxin

    SciTech Connect (OSTI)

    Hausmann, Jens; Kamtekar, Satwik; Christodoulou, Evangelos; Day, Jacqueline E.; Wu, Tao; Fulkerson, Zachary; Albers, Harald M.H.G.; van Meeteren, Laurens A.; Houben, Anna J.S.; van Zeijl, Leonie; Jansen, Silvia; Andries, Maria; Hall, Troii; Pegg, Lyle E.; Benson, Timothy E.; Kasiem, Mobien; Harlos, Karl; Vander Kooi, Craig W.; Smyth, Susan S.; Ovaa, Huib; Bollen, Mathieu; Morris, Andrew J.; Moolenaar, Wouter H.; Perrakis, Anastassis (Pfizer); (Leuven); (Oxford); (NCI-Netherlands); (Kentucky)

    2013-09-25T23:59:59.000Z

    Autotaxin (ATX, also known as ectonucleotide pyrophosphatase/phosphodiesterase-2, ENPP2) is a secreted lysophospholipase D that generates the lipid mediator lysophosphatidic acid (LPA), a mitogen and chemoattractant for many cell types. ATX-LPA signaling is involved in various pathologies including tumor progression and inflammation. However, the molecular basis of substrate recognition and catalysis by ATX and the mechanism by which it interacts with target cells are unclear. Here, we present the crystal structure of ATX, alone and in complex with a small-molecule inhibitor. We have identified a hydrophobic lipid-binding pocket and mapped key residues for catalysis and selection between nucleotide and phospholipid substrates. We have shown that ATX interacts with cell-surface integrins through its N-terminal somatomedin B-like domains, using an atypical mechanism. Our results define determinants of substrate discrimination by the ENPP family, suggest how ATX promotes localized LPA signaling and suggest new approaches for targeting ATX with small-molecule therapeutic agents.

  12. Building Noetherian and non-Noetherian integral domains using ...

    E-Print Network [OSTI]

    2013-06-30T23:59:59.000Z

    valuation domain birationally dominating R, .... discrete valuation domain (DVR) and it is well-known that the completion of R .... two methods for the construction.

  13. Structured hints : extracting and abstracting domain expertise.

    SciTech Connect (OSTI)

    Hereld, M.; Stevens, R.; Sterling, T.; Gao, G. R.; Mathematics and Computer Science; California Inst. of Tech.; Louisiana State Univ.; Univ. of Delaware

    2009-03-16T23:59:59.000Z

    We propose a new framework for providing information to help optimize domain-specific application codes. Its design addresses problems that derive from the widening gap between the domain problem statement by domain experts and the architectural details of new and future high-end computing systems. The design is particularly well suited to program execution models that incorporate dynamic adaptive methodologies for live tuning of program performance and resource utilization. This new framework, which we call 'structured hints', couples a vocabulary of annotations to a suite of performance metrics. The immediate target is development of a process by which a domain expert describes characteristics of objects and methods in the application code that would not be readily apparent to the compiler; the domain expert provides further information about what quantities might provide the best indications of desirable effect; and the interactive preprocessor identifies potential opportunities for the domain expert to evaluate. Our development of these ideas is progressing in stages from case study, through manual implementation, to automatic or semi-automatic implementation. In this paper we discuss results from our case study, an examination of a large simulation of a neural network modeled after the neocortex.

  14. Telegraphic prose: The effects of a subjective deletion scheme on the comprehension and reading rate of blind and sighted students.

    E-Print Network [OSTI]

    Sheffield, Carol Ann

    1972-01-01T23:59:59.000Z

    for a Speci. fied Percentage of Deletion 114 APPENDIX K: Instructions for Phase II ? Passage and Test 115 APPENDIX L: Index of Agreement Among Sighted Ss on the Rank Order of Words Within Each Sentence 119 APPENDIX M: 10, 30, and 50 Percent... Treatment Conditions 50 14 Mean Reading Time (in minutes) and Standard Deviation for Blind and Sighted Ss in Each of the Four Treatment Conditions 51 15 Mean E and Standard Deviation for Blind and Sighted Ss in Each of the Four Treatment Conditions. 53...

  15. Crystal Structures of the Staphylococcal Toxin SSL5 in Complex With Sialyl-Lewis X Reveal a Conserved Binding Site That Shares Common Features With Viral And Bacterial Sialic Acid-Binding Proteins

    SciTech Connect (OSTI)

    Baker, H.M.; Basu, I.; Chung, M.C.; Caradoc-Davies, T.; Fraser, J.D.; Baker, E.N.

    2009-06-02T23:59:59.000Z

    Staphylococcus aureus is a significant human pathogen. Among its large repertoire of secreted toxins is a group of staphylococcal superantigen-like proteins (SSLs). These are homologous to superantigens but do not have the same activity. SSL5 is shown here to bind to human granulocytes and to the cell surface receptors for human IgA (Fc alphaRI) and P-selectin [P-selectin glycoprotein ligand-1 (PSGL-1)] in a sialic acid (Sia)-dependent manner. Co-crystallization of SSL5 with the tetrasaccharide sialyl Lewis X (sLe(X)), a key determinant of PSGL-1 binding to P-selectin, led to crystal structures of the SSL5-sLe(X) complex at resolutions of 1.65 and 2.75 A for crystals at two pH values. In both structures, sLe(X) bound to a specific site on the surface of the C-terminal domain of SSL5 in a conformation identical with that bound by P-selectin. Conservation of the key carbohydrate binding residues indicates that this ability to bind human glycans is shared by a substantial subgroup of the SSLs, including SSL2, SSL3, SSL4, SSL5, SSL6, and SSL11. This indicates that the ability to target human glycans is an important property of this group of toxins. Structural comparisons also showed that the Sia binding site in SSL5 contains a substructure that is shared by other Sia binding proteins from bacteria as well as viruses and represents a common binding motif.

  16. Dual-domain point diffraction interferometer

    DOE Patents [OSTI]

    Naulleau, Patrick P. (5239 Miles Ave., Apt. A, Oakland, CA 94618); Goldberg, Kenneth Alan (1195 Keeler Ave., Berkeley, CA 94708)

    2000-01-01T23:59:59.000Z

    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.

  17. Binding Energies in Nonrelativistic Field Theories

    E-Print Network [OSTI]

    Andreas S. Kronfeld

    1996-08-26T23:59:59.000Z

    Relativistic corrections communicate the binding energy of a bound state to its kinetic mass. This mechanism is reviewed and used to explain anomalous results of Collins, Edwards, Heller, and Sloan (hep-lat/9512026), which compared rest and kinetic masses of heavy-light mesons and quarkonia.

  18. Names and Binding in Type Theory

    E-Print Network [OSTI]

    Schpp, Ulrich

    Names and name-binding are useful concepts in the theory and practice of formal systems. In this thesis we study them in the context of dependent type theory. We propose a novel dependent type theory with primitives for the explicit handling...

  19. Impact on the steam electric power industry of deleting Section 316(a) of the Clean Water Act: Capital costs

    SciTech Connect (OSTI)

    Veil, J.A.

    1993-01-01T23:59:59.000Z

    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 total US steam electric generating capacity 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 describes alternatives available to nuclear and coal-fired plants currently operating under variances. Data from 38 plants representing 14 companies are used to estimate the national cost of implementing such alternatives. Although there are other alternatives, most affected plants would be retrofitted with cooling towers. Assuming that all plants currently operating under variances would install cooling towers, the national capital cost estimate for these retrofits ranges from $22.7 billion to $24.4 billion (in 1992 dollars). The second report quantitatively and qualitatively evaluates the energy and environmental impacts of deleting the variance. Little justification has been found for removing the Section 316(a) variance from the CWA.

  20. Thermodynamics of free Domain Wall fermions

    E-Print Network [OSTI]

    R. V. Gavai; Sayantan Sharma

    2008-11-19T23:59:59.000Z

    Studying various thermodynamic quantities for the free domain wall fermions for both finite and infinite fifth dimensional extent N_5, we find that the lattice corrections are minimum for $N_T\\geq10$ for both energy density and susceptibility, for its irrelevant parameter M in the range 1.45-1.50. The correction terms are, however, quite large for small lattice sizes of $N_T\\leq8$. We propose modifications of the domain wall operator, as well as the overlap operator, to reduce the finite cut-off effects to within 10% of the continuum results of the thermodynamic quantities for the currently used N_T=6-8 lattices. Incorporating chemical potential, we show that \\mu^2 divergences are absent for a large class of such domain wall fermion actions although the chiral symmetry is broken for $\\mu\

  1. The NMDA Receptor NR1 C1 Region Bound to Calmodulin: Structural Insights into Functional Differences between Homologous Domains

    SciTech Connect (OSTI)

    Ataman, Zeynep Akyol; Gakhar, Lokesh; Sorensen, Brenda R.; Hell, Johannes W.; Shea, Madeline A. (Iowa)

    2008-09-17T23:59:59.000Z

    Calmodulin (CaM) regulates tetrameric N-methyl-D-aspartate receptors (NMDARs) by binding tightly to the C0 and C1 regions of its NR1 subunit. A crystal structure (2HQW; 1.96 {angstrom}) of calcium-saturated CaM bound to NR1C1 (peptide spanning 875-898) showed that NR1 S890, whose phosphorylation regulates membrane localization, was solvent protected, whereas the endoplasmic reticulum retention motif was solvent exposed. NR1 F880 filled the CaM C-domain pocket, whereas T886 was closest to the N-domain pocket. This 1-7 pattern was most similar to that in the CaM-MARCKS complex. Comparison of CaM-ligand wrap-around conformations identified a core tetrad of CaM C-domain residues (FLMM{sub C}) that contacted all ligands consistently. An identical tetrad of N-domain residues (FLMM{sub N}) made variable sets of contacts with ligands. This CaM-NR1C1 structure provides a foundation for designing mutants to test the role of CaM in NR1 trafficking as well as insights into how the homologous CaM domains have different roles in molecular recognition.

  2. Structures of the Porphyromonas gingivalis OxyR regulatory domain explain differences in expression of the OxyR regulon in Escherichia coli and P. gingivalis

    SciTech Connect (OSTI)

    Svintradze, David V. [Virginia Commonwealth University, Richmond, VA 23298-0566 (United States); Virginia Commonwealth University, Richmond, VA 23219-1540 (United States); Peterson, Darrell L. [Virginia Commonwealth University, Richmond, VA 23219-1540 (United States); Virginia Commonwealth University, Richmond, VA 23298-0614 (United States); Collazo-Santiago, Evys A.; Lewis, Janina P. [Virginia Commonwealth University, Richmond, VA 23298-0566 (United States); Wright, H. Tonie, E-mail: xrdproc@vcu.edu [Virginia Commonwealth University, Richmond, VA 23219-1540 (United States); Virginia Commonwealth University, Richmond, VA 23298-0614 (United States); Virginia Commonwealth University, Richmond, VA 23298-0566 (United States)

    2013-10-01T23:59:59.000Z

    Differences in OxyR regulated expression of oxidative stress genes between Escherichia coli and Porphyromonas gingivalis are explained by very minor differences in structure and amino-acid sequence of the respective oxidized and reduced OxyR regulatory domains. These differences affect OxyR quaternary structures and are predicted from model building of full length OxyRDNA complexes to confer distinct modes of DNA binding on this transcriptional regulator. OxyR transcriptionally regulates Escherichia coli oxidative stress response genes through a reversibly reducible cysteine disulfide biosensor of cellular redox status. Structural changes induced by redox changes in these cysteines are conformationally transmitted to the dimer subunit interfaces, which alters dimer and tetramer interactions with DNA. In contrast to E. coli OxyR regulatory-domain structures, crystal structures of Porphyromonas gingivalis OxyR regulatory domains show minimal differences in dimer configuration on changes in cysteine disulfide redox status. This locked configuration of the P. gingivalis OxyR regulatory-domain dimer closely resembles the oxidized (activating) form of the E. coli OxyR regulatory-domain dimer. It correlates with the observed constitutive activation of some oxidative stress genes in P. gingivalis and is attributable to a single amino-acid insertion in P. gingivalis OxyR relative to E. coli OxyR. Modelling of full-length P. gingivalis, E. coli and Neisseria meningitidis OxyRDNA complexes predicts different modes of DNA binding for the reduced and oxidized forms of each.

  3. Recombinant fusion protein of albumin-retinol binding protein inactivates stellate cells

    SciTech Connect (OSTI)

    Choi, Soyoung; Park, Sangeun; Kim, Suhyun [Laboratory of Cellular Oncology, Korea University Graduate School of Medicine, Ansan, Gyeonggi do 425-707 (Korea, Republic of)] [Laboratory of Cellular Oncology, Korea University Graduate School of Medicine, Ansan, Gyeonggi do 425-707 (Korea, Republic of); Lim, Chaeseung [Department of Laboratory Medicine, Korea University Guro Hospital, Seoul 152-703 (Korea, Republic of)] [Department of Laboratory Medicine, Korea University Guro Hospital, Seoul 152-703 (Korea, Republic of); Kim, Jungho [Department of Life Science, Sogang University, Seoul 121-742 (Korea, Republic of)] [Department of Life Science, Sogang University, Seoul 121-742 (Korea, Republic of); Cha, Dae Ryong [Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Gyeonggi do 425-020 (Korea, Republic of)] [Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Gyeonggi do 425-020 (Korea, Republic of); Oh, Junseo, E-mail: ohjs@korea.ac.kr [Laboratory of Cellular Oncology, Korea University Graduate School of Medicine, Ansan, Gyeonggi do 425-707 (Korea, Republic of)] [Laboratory of Cellular Oncology, Korea University Graduate School of Medicine, Ansan, Gyeonggi do 425-707 (Korea, Republic of)

    2012-02-03T23:59:59.000Z

    Highlights: Black-Right-Pointing-Pointer We designed novel recombinant albumin-RBP fusion proteins. Black-Right-Pointing-Pointer Expression of fusion proteins inactivates pancreatic stellate cells (PSCs). Black-Right-Pointing-Pointer Fusion proteins are successfully internalized into and inactivate PSCs. Black-Right-Pointing-Pointer RBP moiety mediates cell specific uptake of fusion protein. -- Abstract: Quiescent pancreatic- (PSCs) and hepatic- (HSCs) stellate cells store vitamin A (retinol) in lipid droplets via retinol binding protein (RBP) receptor and, when activated by profibrogenic stimuli, they transform into myofibroblast-like cells which play a key role in the fibrogenesis. Despite extensive investigations, there is, however, currently no appropriate therapy available for tissue fibrosis. We previously showed that the expression of albumin, composed of three homologous domains (I-III), inhibits stellate cell activation, which requires its high-affinity fatty acid-binding sites asymmetrically distributed in domain I and III. To attain stellate cell-specific uptake, albumin (domain I/III) was coupled to RBP; RBP-albumin{sup domain} {sup III} (R-III) and albumin{sup domain} {sup I}-RBP-albumin{sup III} (I-R-III). To assess the biological activity of fusion proteins, cultured PSCs were used. Like wild type albumin, expression of R-III or I-R-III in PSCs after passage 2 (activated PSCs) induced phenotypic reversal from activated to fat-storing cells. On the other hand, R-III and I-R-III, but not albumin, secreted from transfected 293 cells were successfully internalized into and inactivated PSCs. FPLC-purified R-III was found to be internalized into PSCs via caveolae-mediated endocytosis, and its efficient cellular uptake was also observed in HSCs and podocytes among several cell lines tested. Moreover, tissue distribution of intravenously injected R-III was closely similar to that of RBP. Therefore, our data suggest that albumin-RBP fusion protein comprises of stellate cell inactivation-inducing moiety and targeting moiety, which may lead to the development of effective anti-fibrotic drug.

  4. Crystal structure of the anti-viral APOBEC3G catalytic domain and functional implications

    SciTech Connect (OSTI)

    Holden, Lauren G.; Prochnow, Courtney; Chang, Y. Paul; Bransteitter, Ronda; Chelico, Linda; Sen, Udayaditya; Stevens, Raymond C.; Goodman, Myron F.; Chen, Xiaojiang S. (USC); (Scripps)

    2009-04-07T23:59:59.000Z

    The APOBEC family members are involved in diverse biological functions. APOBEC3G restricts the replication of human immunodeficiency virus (HIV), hepatitis B virus and retroelements by cytidine deamination on single-stranded DNA or by RNA binding. Here we report the high-resolution crystal structure of the carboxy-terminal deaminase domain of APOBEC3G (APOBEC3G-CD2) purified from Escherichia coli. The APOBEC3G-CD2 structure has a five-stranded {beta}-sheet core that is common to all known deaminase structures and closely resembles the structure of another APOBEC protein, APOBEC2. A comparison of APOBEC3G-CD2 with other deaminase structures shows a structural conservation of the active-site loops that are directly involved in substrate binding. In the X-ray structure, these APOBEC3G active-site loops form a continuous 'substrate groove' around the active centre. The orientation of this putative substrate groove differs markedly (by 90 degrees) from the groove predicted by the NMR structure. We have introduced mutations around the groove, and have identified residues involved in substrate specificity, single-stranded DNA binding and deaminase activity. These results provide a basis for understanding the underlying mechanisms of substrate specificity for the APOBEC family.

  5. Standing gravitational waves from domain walls

    SciTech Connect (OSTI)

    Gogberashvili, Merab [Andronikashvili Institute of Physics, 6 Tamarashvili Street, Tbilisi 0177 (Georgia); Javakhishvili Tbilisi State University, 3 Chavchavadze Avenue, Tbilisi 0128 (Georgia); California State University, Fresno, Physics Department, Fresno, California 93740-8031 (United States); Myrzakul, Shynaray [Department of General and Theoretical Physics, Gumilev Eurasian National University, Astana, 010008 (Kazakhstan); California State University, Fresno, Physics Department, Fresno, California 93740-8031 (United States); Singleton, Douglas [California State University, Fresno, Physics Department, Fresno, California 93740-8031 (United States); Institute of Gravitation and Cosmology, Peoples' Friendship University of Russia, Moscow 117198 (Russian Federation)

    2009-07-15T23:59:59.000Z

    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.

  6. Antiferromagnetic domain size and exchange bias

    E-Print Network [OSTI]

    Fitzsimmons, M. R.; Lederman, D.; Cheon, M.; Shi, H.; Olamit, J.; Roshchin, Igor V.; Schuller, Ivan K.

    2008-01-01T23:59:59.000Z

    in the adjacent FM was inferred from scanning MOKE spectroscopy and superconducting quantum interfer- ence device #1;SQUID#2; magnetometry. The relationship gov- erns the regime of exchange bias #5;averaging #1;of FM domains over AF domains#2; vs nonaveraging... with neutron reflectometry34 and inferred from magnetometry and micromagnetic model- ing of GdFe/TbFe bilayers.27,35 Despite recent successful efforts to quantify the uncom- pensated magnetization in the AF, measurement of AF do- main size has not been...

  7. U-101: Mozilla Firefox / Thunderbird / SeaMonkey XBL Binding...

    Broader source: Energy.gov (indexed) [DOE]

    101: Mozilla Firefox Thunderbird SeaMonkey XBL Binding Use-After-Free Vulnerability U-101: Mozilla Firefox Thunderbird SeaMonkey XBL Binding Use-After-Free Vulnerability...

  8. acid binding proteins: Topics by E-print Network

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

    The adipocyte fatty acid-binding protein aP2 regulates systemic glucose (more) Shum, Bennett Oh Vic 2007-01-01 2 Fatty acid-binding protein in bovine skeletal muscle Texas A&M...

  9. acid dopac binds: Topics by E-print Network

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

    The adipocyte fatty acid-binding protein aP2 regulates systemic glucose (more) Shum, Bennett Oh Vic 2007-01-01 2 Fatty acid-binding protein in bovine skeletal muscle Texas A&M...

  10. Conformation Changes N-terminal Involvement and cGMP Signal Relay in the Phosphodiesterase-5 GAF Domain

    SciTech Connect (OSTI)

    H Wang; H Robinson; H Ke

    2011-12-31T23:59:59.000Z

    The activity of phosphodiesterase-5 (PDE5) is specific for cGMP and is regulated by cGMP binding to GAF-A in its regulatory domain. To better understand the regulatory mechanism, x-ray crystallographic and biochemical studies were performed on constructs of human PDE5A1 containing the N-terminal phosphorylation segment, GAF-A, and GAF-B. Superposition of this unliganded GAF-A with the previously reported NMR structure of cGMP-bound PDE5 revealed dramatic conformational differences and suggested that helix H4 and strand B3 probably serve as two lids to gate the cGMP-binding pocket in GAF-A. The structure also identified an interfacial region among GAF-A, GAF-B, and the N-terminal loop, which may serve as a relay of the cGMP signal from GAF-A to GAF-B. N-terminal loop 98-147 was physically associated with GAF-B domains of the dimer. Biochemical analyses showed an inhibitory effect of this loop on cGMP binding and its involvement in the cGMP-induced conformation changes.

  11. Study of fragmentation using clusterization algorithm with realistic binding energies

    E-Print Network [OSTI]

    Yogesh K. Vermani; Jatinder K. Dhawan; Supriya Goyal; Rajeev K. Puri; J. Aichelin

    2009-12-28T23:59:59.000Z

    We here study fragmentation using \\emph{simulated annealing clusterization algorithm} (SACA) with binding energy at a microscopic level. In an earlier version, a constant binding energy (4 MeV/nucleon) was used. We improve this binding energy criterion by calculating the binding energy of different clusters using modified Bethe-Weizs\\"{a}cker mass (BWM) formula. We also compare our calculations with experimental data of ALADiN group. Nearly no effect is visible of this modification.

  12. Assignment of the Four Disulfides in the N-terminal Somatomedin B Domain of Native Vitronectin Isolated from Human Plasma

    SciTech Connect (OSTI)

    Horn, Nancy A [University of Tennessee, Knoxville (UTK); Hurst, Gregory {Greg} B [ORNL; Mayasundari, Anand [University of Tennessee, Knoxville (UTK); Whittemore, Neil A [University of Tennessee, Knoxville (UTK); Serpersu, Engin H [University of Tennessee, Knoxville (UTK); Peterson, Cynthia B [University of Tennessee, Knoxville (UTK)

    2004-01-01T23:59:59.000Z

    The primary sequence of the N-terminal somatomedin B (SMB) domain of native vitronectin contains 44 amino acids, including a framework of four disulfide bonds formed by 8 closely spaced cysteines in sequence patterns similar to those found in the cystine knot family of proteins. The SMB domain of vitronectin was isolated by digesting the protein with endoproteinase Glu-C and purifying the N-terminal 1-55 peptide by reverse-phase high performance liquid chromatography. Through a combination of techniques, including stepwise reduction and alkylation at acidic pH, peptide mapping with matrix-assisted laser desorption ionization mass spectrometry and NMR, the disulfide bonds contained in the SMB domain have been determined to be Cys{sup 5}:Cys{sup 9}, Cys{sup 19}:Cys{sup 31}, Cys{sup 21}:Cys{sup 32}, and Cys{sup 25}:Cys{sup 39}. This pattern of disulfides differs from two other connectivities that have been reported previously for recombinant forms of the SMB domain expressed in Escherichia coli. This arrangement of disulfide bonds in the SMB domain from native vitronectin forms a rigid core around the Cys{sup 19}: Cys{sup 31} and Cys{sup 21}:Cys{sup 32} disulfides. A small positively charged loop is created at the N terminus by the Cys{sup 5}: Cys{sup 9} cystine. The most prominent feature of this disulfide-bonding pattern is a loop between Cys{sup 25} and Cys{sup 39} similar to cystine-stabilized {alpha}-helical structures commonly observed in cystine knots. This {alpha}-helix has been confirmed in the solution structure determined for this domain using NMR (Mayasundari, A., Whittemore, N. A., Serpersu, E. H., and Peterson, C. B. (2004) J. Biol. Chem. 279, 29359-29366). It confers function on the SMB domain, comprising the site for binding to plasminogen activator inhibitor type-1 and the urokinase receptor.

  13. September 18, 1994 A Binding Architecture for Multimedia Networks

    E-Print Network [OSTI]

    Columbia University

    1 September 18, 1994 A Binding Architecture for Multimedia Networks Aurel A. Lazar , Shailendra K of a set of interfaces, methods and primitives. The former abstract the functionalities of multimedia for implementing binding applications. The binding architecture is embedded into a reference model for multimedia

  14. Domain wall partition functions and KP

    E-Print Network [OSTI]

    O Foda; M Wheeler; M Zuparic

    2009-01-15T23:59:59.000Z

    We observe that the partition function of the six vertex model on a finite square lattice with domain wall boundary conditions is (a restriction of) a KP tau function and express it as an expectation value of charged free fermions (up to an overall normalization).

  15. Solitons and Domain Walls in Odd Dimensions

    E-Print Network [OSTI]

    N. D. Lambert; G. W. Gibbons

    2000-07-04T23:59:59.000Z

    We discuss the existance of smooth soliton solutions which interpolate between supersymmetric vacua in odd-dimensional theories. In particular we apply this analysis to a wide class of supergravities to argue against the existence of smooth domain walls interpolating between supersymmetric vacua. We find that if the superpotential changes sign then any Goldstino modes will diverge.

  16. Large power grid analysis using domain decomposition

    E-Print Network [OSTI]

    Mohanram, Kartik

    -scale linear circuits such as power distribution networks. Simulation results show that by inte- grating the proposed DD framework, existing linear circuit simulators can be extended to handle otherwise intractableLarge power grid analysis using domain decomposition Quming Zhou, Kai Sun, Kartik Mohanram, Danny C

  17. Tight Binding Hamiltonians and Quantum Turing Machines

    E-Print Network [OSTI]

    Paul Benioff

    1996-10-17T23:59:59.000Z

    This paper extends work done to date on quantum computation by associating potentials with different types of computation steps. Quantum Turing machine Hamiltonians, generalized to include potentials, correspond to sums over tight binding Hamiltonians each with a different potential distribution. Which distribution applies is determined by the initial state. An example, which enumerates the integers in succession as binary strings, is analyzed. It is seen that for some initial states the potential distributions have quasicrystalline properties and are similar to a substitution sequence.

  18. 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., E-mail: mohansepuri@gmail.com; Gupta, Arun A., E-mail: ninja14gupta@gmail.com; Yu, Chin, E-mail: cyu.nthu@gmail.com

    2013-05-03T23:59:59.000Z

    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 S100A6mRAGE V domain binding were mapped by {sup 1}H{sup 15}N HSQC titration. S100A6RAGE V domain tetrameric complex model was generated from NMR studies. The S100A6RAGE 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 S100A6mRAGE V domain complex. This model provides an important insights into the S100RAGE cellular signaling pathway.

  19. Deletion of P399{sub E}401 in NADPH cytochrome P450 oxidoreductase results in partial mixed oxidase deficiency

    SciTech Connect (OSTI)

    Flueck, Christa E., E-mail: christa.flueck@dkf.unibe.ch [Pediatric Endocrinology, Diabetology and Metabolism, University Children's Hospital, Bern (Switzerland); Mallet, Delphine [Service d'Endocrinologie Moleculaire et Maladies Rares, Hospices Civils de Lyon, Bron (France)] [Service d'Endocrinologie Moleculaire et Maladies Rares, Hospices Civils de Lyon, Bron (France); Hofer, Gaby [Pediatric Endocrinology, Diabetology and Metabolism, University Children's Hospital, Bern (Switzerland)] [Pediatric Endocrinology, Diabetology and Metabolism, University Children's Hospital, Bern (Switzerland); Samara-Boustani, Dinane [Hopital Necker-Enfants malades, Paris (France)] [Hopital Necker-Enfants malades, Paris (France); Leger, Juliane [Hopital Robert Debre, Paris (France)] [Hopital Robert Debre, Paris (France); Polak, Michel [Hopital Necker-Enfants malades, Paris (France)] [Hopital Necker-Enfants malades, Paris (France); Morel, Yves [Service d'Endocrinologie Moleculaire et Maladies Rares, Hospices Civils de Lyon, Bron (France)] [Service d'Endocrinologie Moleculaire et Maladies Rares, Hospices Civils de Lyon, Bron (France); Pandey, Amit V., E-mail: amit@pandeylab.org [Pediatric Endocrinology, Diabetology and Metabolism, University Children's Hospital, Bern (Switzerland)

    2011-09-09T23:59:59.000Z

    Highlights: {yields} Mutations in human POR cause congenital adrenal hyperplasia. {yields} We are reporting a novel 3 amino acid deletion mutation in POR P399{sub E}401del. {yields} POR mutation P399{sub E}401del decreased P450 activities by 60-85%. {yields} Impairment of steroid metabolism may be caused by multiple hits. {yields} Severity of aromatase inhibition is related to degree of in utero virilization. -- Abstract: P450 oxidoreductase (POR) is the electron donor for all microsomal P450s including steroidogenic enzymes CYP17A1, CYP19A1 and CYP21A2. We found a novel POR mutation P399{sub E}401del in two unrelated Turkish patients with 46,XX disorder of sexual development. Recombinant POR proteins were produced in yeast and tested for their ability to support steroid metabolizing P450 activities. In comparison to wild-type POR, the P399{sub E}401del protein was found to decrease catalytic efficiency of 21-hydroxylation of progesterone by 68%, 17{alpha}-hydroxylation of progesterone by 76%, 17,20-lyase action on 17OH-pregnenolone by 69%, aromatization of androstenedione by 85% and cytochrome c reduction activity by 80%. Protein structure analysis of the three amino acid deletion P399{sub E}401 revealed reduced stability and flexibility of the mutant. In conclusion, P399{sub E}401del is a novel mutation in POR that provides valuable genotype-phenotype and structure-function correlation for mutations in a different region of POR compared to previous studies. Characterization of P399{sub E}401del provides further insight into specificity of different P450s for interaction with POR as well as nature of metabolic disruptions caused by more pronounced effect on specific P450s like CYP17A1 and aromatase.

  20. A comparison of marine time-domain and frequency-domain controlled source electromagnetic methods

    E-Print Network [OSTI]

    Connell, Dylan

    2011-01-01T23:59:59.000Z

    The inline step-on and step-off response for the canonicalD) and time-domain (step-on) responses for various levels of180 s. stacking), step-on response (500 stacks), and PRBS (

  1. Assessing a potential correlation between protein stability and function of the HMG domain of Lymphoid Enhancer Binding Factor-1

    E-Print Network [OSTI]

    Ly, Youly

    2012-01-01T23:59:59.000Z

    of LEF1 in T-cell acute lymphoblastic leukemia. Blood 115,pathways in T cell acute lymphoblastic leukemia. Cancer Cellsuch as T-cell acute lymphoblastic leukemia (T-ALL). T-ALL

  2. The Ligand Binding Domain of GCNF Is Not Required for Repression of Pluripotency Genes in Mouse Fetal Ovarian Germ Cells

    E-Print Network [OSTI]

    Okumura, Leah M.

    In mice, successful development and reproduction require that all cells, including germ cells, transition from a pluripotent to a differentiated state. This transition is associated with silencing of the pluripotency genes ...

  3. Autoradiographic localization of endothelin-1 binding sites in porcine skin

    SciTech Connect (OSTI)

    Zhao, Y.D.; Springall, D.R.; Wharton, J.; Polak, J.M. (Royal Postgraduate Medical School, London (England))

    1991-01-01T23:59:59.000Z

    Autoradiographic techniques and {sup 125}I-labeled endothelin-1 were used to study the distribution of endothelin-1 binding sites in porcine skin. Specific endothelin-1 binding sites were localized to blood vessels (capillaries, deep cutaneous vascular plexus, arteries, and arterioles), the deep dermal and connective tissue sheath of hair follicles, sebaceous and sweat glands, and arrector pili muscle. Specific binding was inhibited by endothelin-2 and endothelin-3 as well as endothelin-1. Non-specific binding was found in the epidermis and the medulla of hair follicles. No binding was found in connective tissue or fat. These vascular binding sites may represent endothelin receptors, in keeping with the known cutaneous vasoconstrictor actions of the peptide. If all binding sites are receptors, the results suggest that endothelin could also regulate the function of sweat glands and may have trophic effects in the skin.

  4. Both common variations and rare non-synonymous substitutions and small insertion/deletions in CLU are associated with increased Alzheimer risk

    E-Print Network [OSTI]

    Bettens, Karolien; Brouwers, Nathalie; Engelborghs, Sebastiaan; Lambert, Jean-Charles; Rogaeva, Ekaterina; Vandenberghe, Rik; Le Bastard, Nathalie; Pasquier, Florence; Vermeulen, Steven; Van Dongen, Jasper; Mattheijssens, Maria; Peeters, Karin; Mayeux, Richard; St George-Hyslop, Peter; Amouyel, Philippe; De Deyn, Peter P; Sleegers, Kristel; Van Broeckhoven, Christine

    2012-01-16T23:59:59.000Z

    insertion/deletions. A meta-analysis, combining the datasets of the 3 cohorts with published CLU sequencing data, confirmed that rare coding variations in the CLU ?-chain were significantly enriched in AD patients (ORMH = 1.96 [95% CI = 1.18-3.25]; p = 0...

  5. ANDERSON-TEIXEIRA FINAL PROOF.DOCX (DO NOT DELETE) 3/7/2011 9:29 AM DO BIOFUELS LIFE CYCLE

    E-Print Network [OSTI]

    DeLucia, Evan H.

    ANDERSON-TEIXEIRA FINAL PROOF.DOCX (DO NOT DELETE) 3/7/2011 9:29 AM 589 DO BIOFUELS LIFE CYCLE ANALYSES ACCURATELY QUANTIFY THE CLIMATE IMPACTS OF BIOFUELS-RELATED LAND USE CHANGE? Kristina J. Anderson in determining the sustainability of biofuels. To ensure that legal standards are effective in limiting climate

  6. Two Distinct Binding Modes Define the Interaction of Brox with the C-Terminal Tails of CHMP5 and CHMP4B

    SciTech Connect (OSTI)

    Mu, Ruiling; Dussupt, Vincent; Jiang, Jiansheng; Sette, Paola; Rudd, Victoria; Chuenchor, Watchalee; Bello, Nana F.; Bouamr, Fadila; Xiao, Tsan Sam (NIH)

    2012-05-21T23:59:59.000Z

    Interactions of the CHMP protein carboxyl terminal tails with effector proteins play important roles in retroviral budding, cytokinesis, and multivesicular body biogenesis. Here we demonstrate that hydrophobic residues at the CHMP4B C-terminal amphipathic {alpha} helix bind a concave surface of Brox, a mammalian paralog of Alix. Unexpectedly, CHMP5 was also found to bind Brox and specifically recruit endogenous Brox to detergent-resistant membrane fractions through its C-terminal 20 residues. Instead of an {alpha} helix, the CHMP5 C-terminal tail adopts a tandem {beta}-hairpin structure that binds Brox at the same site as CHMP4B. Additional Brox:CHMP5 interface is furnished by a unique CHMP5 hydrophobic pocket engaging the Brox residue Y348 that is not conserved among the Bro1 domains. Our studies thus unveil a {beta}-hairpin conformation of the CHMP5 protein C-terminal tail, and provide insights into the overlapping but distinct binding profiles of ESCRT-III and the Bro1 domain proteins.

  7. Crystal Structure of the C-terminal Region of Streptococcus mutans Antigen I/II and Characterization of Salivary Agglutinin Adherence Domains

    SciTech Connect (OSTI)

    Larson, Matthew R.; Rajashankar, Kanagalaghatta R.; Crowley, Paula J.; Kelly, Charles; Mitchell, Tim J.; Brady, L. Jeannine; Deivanayagam, Champion (King); (Cornell); (UAB); (Glasgow); (Florida)

    2012-05-29T23:59:59.000Z

    The Streptococcus mutans antigen I/II (AgI/II) is a cell surface-localized protein that adheres to salivary components and extracellular matrix molecules. Here we report the 2.5 {angstrom} resolution crystal structure of the complete C-terminal region of AgI/II. The C-terminal region is comprised of three major domains: C{sub 1}, C{sub 2}, and C{sub 3}. Each domain adopts a DE-variant IgG fold, with two {beta}-sheets whose A and F strands are linked through an intramolecular isopeptide bond. The adherence of the C-terminal AgI/II fragments to the putative tooth surface receptor salivary agglutinin (SAG), as monitored by surface plasmon resonance, indicated that the minimal region of binding was contained within the first and second DE-variant-IgG domains (C{sub 1} and C{sub 2}) of the C terminus. The minimal C-terminal region that could inhibit S. mutans adherence to SAG was also confirmed to be within the C{sub 1} and C{sub 2} domains. Competition experiments demonstrated that the C- and N-terminal regions of AgI/II adhere to distinct sites on SAG. A cleft formed at the intersection between these C{sub 1} and C{sub 2} domains bound glucose molecules from the cryo-protectant solution, revealing a putative binding site for its highly glycosylated receptor SAG. Finally, electron microscopy images confirmed the elongated structure of AgI/II and enabled building a composite tertiary model that encompasses its two distinct binding regions.

  8. LHC RF System Time-Domain Simulation

    SciTech Connect (OSTI)

    Mastorides, T.; Rivetta, C.; /SLAC

    2010-09-14T23:59:59.000Z

    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.

  9. Budding of domains in mixed bilayer membranes

    E-Print Network [OSTI]

    Jean Wolff; Shigeyuki Komura; David Andelman

    2015-01-10T23:59:59.000Z

    We propose a model that accounts for budding behavior of domains in lipid bilayers, where each of the bilayer leaflets has a coupling between its local curvature and local lipid composition. The compositional asymmetry between the two monolayers leads to an overall spontaneous curvature. The membrane free-energy contains three contributions: bending energy, line tension, and a Landau free-energy for a lateral phase separation. Within a mean-field treatment, we obtain various phase diagrams which contain fully-budded, dimpled and flat states. In particular, for some range of membrane parameters, the phase diagrams exhibit a tricritical behavior as well as three-phase coexistence region. The global phase diagrams can be divided into three types and are analyzed in terms of the curvature-composition coupling parameter and domain size.

  10. Light quark masses using domain wall fermions

    E-Print Network [OSTI]

    Tom Blum; Amarjit Soni; Matthew Wingate

    1998-09-10T23:59:59.000Z

    We compute the one-loop self-energy correction to the massive domain wall quark propagator. Combining this calculation with simulations at several gauge couplings, we estimate the strange quark mass in the continuum limit. The perturbative one-loop mass renormalization is comparable to that for Wilson quarks and considerably smaller than that for Kogut-Susskind quarks. Also, scaling violations appear mild in comparison to other errors at present. Given their good chiral behavior and these features, domain wall quarks are attractive for evaluating the light quark masses. Our preliminary quenched result is m_s(2 GeV) = 82(15) MeV in the ${\\bar{MS}}$ scheme.

  11. Fluctuation induced interactions between domains in membranes

    E-Print Network [OSTI]

    D. S. Dean; M. Manghi

    2006-09-06T23:59:59.000Z

    We study a model lipid bilayer composed of a mixture of two incompatible lipid types which have a natural tendency to segregate in the absence of membrane fluctuations. The membrane is mechanically characterized by a local bending rigidity $\\kappa(\\phi)$ which varies with the average local lipid composition $\\phi$. We show, in the case where $\\kappa$ varies weakly with $\\phi$, that the effective interaction between lipids of the same type can either be everywhere attractive or can have a repulsive component at intermediate distances greater than the typical lipid size. When this interaction has a repulsive component, it can prevent macro-phase separation and lead to separation in mesophases with a finite domain size. This effect could be relevant to certain experimental and numerical observations of mesoscopic domains in such systems.

  12. Electrical signature of magnetic domain-wall dynamics

    E-Print Network [OSTI]

    Liu, Y.; Tretiakov, O. A.; Abanov, Artem.

    2011-01-01T23:59:59.000Z

    Current-induced domain-wall dynamics is studied in a thin ferromagnetic nanowire. The domain-wall dynamics is described by simple equations with four parameters. We propose a procedure to unambiguously determine these parameters by all...

  13. Examples of integral domains inside power series rings

    E-Print Network [OSTI]

    Tx is flat, the associated nested union domain B is Noetherian. ..... Intermediate rings between a local domain and its completion, Illinois J. Math. 43 (1999) ... Department of Mathematics, Purdue University, West Lafayette, IN 47907-1395.

  14. COII/tRNA[sup Lys] intergenic 9-bp deletion and other mtDNA markers clearly reveal that the Tharus (Southern Nepal) have oriental affinities

    SciTech Connect (OSTI)

    Passarino, G.; Semino, O.; Santachiara-Benerecetti, A.S.; Modiano, G. (Universita di Tor Vergata (Romania))

    1993-09-01T23:59:59.000Z

    The authors searched for the East Asian mtDNA 9-bp deletion in the intergenic COII/tRNA[sup Lys] region in a sample of 107 Tharus (50 from central Terai and 57 from eastern Terai), a population whose anthropological origin has yet to be completely clarified. The deletion, detected by electrophoresis of the PCR-amplified nt 7392-8628 mtDNA fragment after digestion with HaeIII, was found in about 8% of both Tharu groups but was found in none of the 76 Hindus who were examined as a non-Oriental neighboring control population. A complete triplication of the 9-bp unit, the second case so far reported, was also observed in one eastern Tharu. All the mtDNAs with the deletion, and that with the triplication, were further characterized (by PCR amplification of the relevant mTDNA fragments and their digestion with the appropriate enzymes) to locate them in the Ballinger et al. phylogeny of East Asian mtDNA haplotypes. The deletion was found to be associated with four different haplotypes, two of which are reported for the first time. One of the deletions and especially the triplication could be best explained by the assumption of novel length-change events. Ballinger's classification of East Asian mtDNA haplotypes is mainly based on the phenotypes for the DdeI site at nt 10394 and the AluI site at nt 10397. Analysis of the entire Tharu sample revealed that more than 70% of the Tharus have both sites, the association of which has been suggested as an ancient East Asian peculiarity. These results conclusively indicate that the Tharus have a predominantly maternal Oriental ancestry. Moreover, they show at least one and perhaps two further distinct length mutations, and this suggests that the examined region is a hot spot of rearrangements. 21 refs., 5 figs., 6 tabs.

  15. Structure of the NS1 Protein N-Terminal Origin Recognition/Nickase Domain from the Emerging Human Bocavirus

    E-Print Network [OSTI]

    Tewary, Sunil Kumar; Zhao, Haiyan; Shen, Weiran; Qiu, Jianming; Tang, Liang

    2013-08-21T23:59:59.000Z

    of 1 mM. Cells were harvested after 16 h of growth and lysed on a French press in resuspension buffer (50 mM Na2HPO4/NaH2PO4 [pH 7.2], 500 mM NaCl, 10% glycerol, and 5mM#2;-mercaptoethanol). The proteinwas purifiedwith a Ni-NTA column (Qiagen), followed...). This indicates that bocaviruses use a conserved mode of NS1-Ori rec- ognition, which is distinct from that of dependoviruses. In AAV, it was proposed that binding of multiple Rep molecules at the Ori would trigger oligomerization of the helicase domain, leading...

  16. Tight Binding Hamiltonians and Quantum Turing Machines

    SciTech Connect (OSTI)

    Benioff, P. [Physics Division, Argonne National Laboratory, Argonne, Illinois 60439 (United States)] [Physics Division, Argonne National Laboratory, Argonne, Illinois 60439 (United States)

    1997-01-01T23:59:59.000Z

    This paper extends work done to date on quantum computation by association of potentials with different types of steps. Quantum Turing machine Hamiltonians, generalized to include potentials, correspond to sums over tight binding Hamiltonians each with a different potential distribution. Which distribution applies is determined by the initial state. An example, which enumerates the integers in succession as binary strings, is analyzed. It is seen that for some initial states, the potential distributions have quasicrystalline properties and are similar to a substitution sequence. {copyright} {ital 1997} {ital The American Physical Society}

  17. Gene encoding herbicide safener binding protein

    DOE Patents [OSTI]

    Walton, Jonathan D. (East Lansing, MI); Scott-Craig, John S. (East Lansing, MI)

    1999-01-01T23:59:59.000Z

    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.

  18. Polynucleotides encoding TRF1 binding proteins

    DOE Patents [OSTI]

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

    2002-01-01T23:59:59.000Z

    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.

  19. Structural analysis of a 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase with an N-terminal chorismate mutase-like regulatory domain

    SciTech Connect (OSTI)

    Light, Samuel H.; Halavaty, Andrei S.; Minasov, George; Shuvalova, Ludmilla; Anderson, Wayne F. (NWU)

    2012-06-27T23:59:59.000Z

    3-Deoxy-D-arabino-heptulosonate 7-phosphate synthase (DAHPS) catalyzes the first step in the biosynthesis of a number of aromatic metabolites. Likely because this reaction is situated at a pivotal biosynthetic gateway, several DAHPS classes distinguished by distinct mechanisms of allosteric regulation have independently evolved. One class of DAHPSs contains a regulatory domain with sequence homology to chorismate mutase - an enzyme further downstream of DAHPS that catalyzes the first committed step in tyrosine/phenylalanine biosynthesis - and is inhibited by chorismate mutase substrate (chorismate) and product (prephenate). Described in this work, structures of the Listeria monocytogenes chorismate/prephenate regulated DAHPS in complex with Mn{sup 2+} and Mn{sup 2+} + phosphoenolpyruvate reveal an unusual quaternary architecture: DAHPS domains assemble as a tetramer, from either side of which chorismate mutase-like (CML) regulatory domains asymmetrically emerge to form a pair of dimers. This domain organization suggests that chorismate/prephenate binding promotes a stable interaction between the discrete regulatory and catalytic domains and supports a mechanism of allosteric inhibition similar to tyrosine/phenylalanine control of a related DAHPS class. We argue that the structural similarity of chorismate mutase enzyme and CML regulatory domain provides a unique opportunity for the design of a multitarget antibacterial.

  20. WELL-CENTERED OVERRINGS OF AN INTEGRAL DOMAIN

    E-Print Network [OSTI]

    Heinzer, William

    WELL-CENTERED OVERRINGS OF AN INTEGRAL DOMAIN William Heinzer Department of Mathematics, Purdue of A if and only if B is flat and well-centered over A. If the integral closure of A is a Krull domain in Theorem 3.6 that every finitely generated well-centered over- ring of an integrally closed domain is flat

  1. The Description Logic ALCN HR+ Extended with Concrete Domains

    E-Print Network [OSTI]

    Moeller, Ralf

    The Description Logic ALCN HR+ Extended with Concrete Domains: A Practically Motivated Approach, role hierarchies, transitively closed roles, generalized concept inclusions, and concrete domains. As in other languages based on concrete domains (e.g. ALC(D)) a so-called ex- istential predicate restriction

  2. Adapting Optimization Techniques to Description Logics with Concrete Domains

    E-Print Network [OSTI]

    Haarslev, Volker

    Adapting Optimization Techniques to Description Logics with Concrete Domains Anni-Yasmin Turhan backtracking and model merging can be adapted to description logics with concrete domains. We propose al) a new requirement for concrete domains in order to enable dependency directed backtracking for all clash

  3. The Description Logic ALCNHR + Extended with Concrete Domains

    E-Print Network [OSTI]

    Haarslev, Volker

    The Description Logic ALCNHR + Extended with Concrete Domains: A Practically Motivated Approach restrictions, role hierarchies, transitively closed roles, generalized concept inclusions, and concrete domains. As in other languages based on concrete domains (e.g. ALC(D)) a so­called ex­ istential predicate restriction

  4. Adapting Optimization Techniques to Description Logics with Concrete Domains

    E-Print Network [OSTI]

    Haarslev, Volker

    Adapting Optimization Techniques to Description Logics with Concrete Domains Anni­Yasmin Turhan backtracking and model merging can be adapted to description logics with concrete domains. We propose al) a new requirement for concrete domains in order to enable dependency directed backtracking for all clash

  5. Activation of G Protein-Coupled Receptor Kinase 1 Involves Interactions between Its N-Terminal Region and Its Kinase Domain

    SciTech Connect (OSTI)

    Huang, Chih-chin; Orban, Tivadar; Jastrzebska, Beata; Palczewski, Krzysztof; Tesmer, John J.G. (Case Western); (Michigan)

    2012-03-16T23:59:59.000Z

    G protein-coupled receptor kinases (GRKs) phosphorylate activated G protein-coupled receptors (GPCRs) to initiate receptor desensitization. In addition to the canonical phosphoacceptor site of the kinase domain, activated receptors bind to a distinct docking site that confers higher affinity and activates GRKs allosterically. Recent mutagenesis and structural studies support a model in which receptor docking activates a GRK by stabilizing the interaction of its 20-amino acid N-terminal region with the kinase domain. This interaction in turn stabilizes a closed, more active conformation of the enzyme. To investigate the importance of this interaction for the process of GRK activation, we first validated the functionality of the N-terminal region in rhodopsin kinase (GRK1) by site-directed mutagenesis and then introduced a disulfide bond to cross-link the N-terminal region of GRK1 with its specific binding site on the kinase domain. Characterization of the kinetic and biophysical properties of the cross-linked protein showed that disulfide bond formation greatly enhances the catalytic efficiency of the peptide phosphorylation, but receptor-dependent phosphorylation, Meta II stabilization, and inhibition of transducin activation were unaffected. These data indicate that the interaction of the N-terminal region with the kinase domain is important for GRK activation but does not dictate the affinity of GRKs for activated receptors.

  6. Long-range Fourier domain optical coherence tomography of the pediatric subglottis

    E-Print Network [OSTI]

    2015-01-01T23:59:59.000Z

    cat e/ijp o r l Long-range Fourier domain optical coherencechild remains intubated. Fourier domain optical coherencesec). Frequency, or Fourier, domain swept source OCT (

  7. A model for positron binding to polar molecules

    E-Print Network [OSTI]

    Gribakin, G F

    2015-01-01T23:59:59.000Z

    A model for positron binding to polar molecules is considered by combining the dipole potential outside the molecule with a strongly repulsive core of a given radius. Using existing experimental data on binding energies leads to unphysically small core radii for all of the molecules studied. This suggests that electron-positron correlations neglected in the simple model play a large role in determining the binding energy. We account for these by including polarization potential via perturbation theory. The improved model enables reliable predictions of binding energies to be made for a range of polar organic molecules and hydrogen cyanide, whose binding energy is known from accurate quantum chemistry calculations. The model explains the linear dependence of the binding energies on the polarizability inferred from the experimental data [Danielson et al 2009 J. Phys. B: At. Mol. Opt. Phys. 42 235203].

  8. HIV evolution in early infection: selection pressures, patterns of insertion and deletion, and the impact of apobec

    SciTech Connect (OSTI)

    Korber, Bette [Los Alamos National Laboratory; Bhattacharya, Tanmoy [Los Alamos National Laboratory; Giorgi, Elena [Los Alamos National Laboratory; Gaschen, B [Los Alamos National Laboratory; Daniels, M [Los Alamos National Laboratory

    2009-01-01T23:59:59.000Z

    The pattern of viral diversification in newly infected individuals provides information about the host environment and immune responses typically experienced by the newly transmitted virus. For example, sites that tend to evolve rapidly across multiple early-infection patients could be involved in enabling escape from common early immune responses, represent adaptation for rapid growth in a newly infected host, or reversion from less fit forms of the virus that were selected for immune escape in previous hosts. Here we investigated the diversification of HIV -I env coding sequences in 81 very early B SUbtype infections previously shown to have resulted from transmission or expansion of single viruses (n=78) or two closely related viruses (n=3). In these cases the sequence of the infecting virus can be estimated accurately, enabling inference of both the direction of substitutions as well as distinction between insertion and deletion events. By integrating information across multiple acutely infected hosts, we find evidence of adaptive evolution of HIV-1 envand identified a subset of codon sites that diversified more rapidly than can be explained by a model of neutral evolution. Of 24 such rapidly diversifying sites, 14 were either (i) clustered and embedded in CTL epitopes that were verified experimentally or predicted based on the individual's HLA or (ii) in a nucleotide context indicative of APOBEC mediated G-to-A substitutions, despite having excluded heavily hypermutated sequences prior to the analysis. In several cases, a rapidly evolving site was both embedded in an APOBEC motif and in a CTL epitope, suggesting that APOBEC may facilitate early immune escape. Ten rapidly diversifying sites could not be explained by CTL escape or APOBEC hypermutation, including the most frequently mutated site, in the fusion peptide of gp4l. We also examined the distribution, extent, and sequence context of insertions and deletions and provide evidence that the length variation seen in hypervariable loop regions of the envelope glycoprotein is a consequence of selection and not mutational hotspots. These results provide a detailed view of the process of diversification of HIV-1 following transmission.

  9. 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.

  10. acid binding protein: Topics by E-print Network

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

    Richardson, Charles C. 17 Acidic pH Changes Receptor Binding Specificity of Helicobacter pylori: a Binary Adhesion Model in which Surface Heat Shock (Stress) Proteins...

  11. Correlation between fundamental binding forces and clinical prognosis...

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

    Atomic force microscopy was used to fish for binding reactions between a fibronectin-coated probe (i.e., substrate simulating an implant device) and each of 15...

  12. Crown Ethers in Graphene Bring Strong, Selective Binding | ornl...

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

    Materials Characterization Crown Ethers in Graphene Bring Strong, Selective Binding November 14, 2014 Schematic showing a graphene sheet containing an array of ideal crown ethers....

  13. Crown Ethers Flatten in Graphene for Strong, Specific Binding...

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

    SHARE Crown Ethers Flatten in Graphene for Strong, Specific Binding ORNL discovery holds potential for separations, sensors, batteries, biotech and more This sheet of graphene...

  14. antigen papillomavirus binding: Topics by E-print Network

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

    specificity, the present set of studies undertook similar goals by Corradin; Jacques M. Chiller 1979-01-01 124 Human Erythrocytes Selectively Bind and Enrich Infectious HIV-1...

  15. antigen binding repertoire: Topics by E-print Network

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

    specificity, the present set of studies undertook similar goals by Corradin; Jacques M. Chiller 1979-01-01 127 Human Erythrocytes Selectively Bind and Enrich Infectious HIV-1...

  16. antigen binds phosphatase: Topics by E-print Network

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

    specificity, the present set of studies undertook similar goals by Corradin; Jacques M. Chiller 1979-01-01 139 Human Erythrocytes Selectively Bind and Enrich Infectious HIV-1...

  17. Binding Energy of d Transition Metals to Alkenes By Wave...

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

    Energy of d Transition Metals to Alkenes By Wave Function Theory and Density Functional Theory. Binding Energy of d Transition Metals to Alkenes By Wave Function Theory...

  18. atomic binding energy: Topics by E-print Network

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

    Calvin W. Johnson; Joshua T. Staker 2012-08-30 2 Estimating ProteinLigand Binding Free Energy: Atomic Solvation Parameters for Partition Coefficient and Biotechnology...

  19. Limit Domains in Several Complex Variables

    E-Print Network [OSTI]

    Console, Alexander

    2013-12-31T23:59:59.000Z

    sequence of automor- phisms" in [Fornss & Stensnes, 2004], both the approaches to constructing Fatou-Bieberbach domains discussed above can be seen as constructing basins of attraction. We will not pursue this viewpoint. 3.2 Push-Out Constructions... n ? N and z ??n and k > m? n. Then writing w = Gm(z) ? Dm, a) and b) 17 imply |Gk(z)?Gm(z)|= |Hk ?Hk?1 ? ?Hm+1(w)?w| ? |w?Hm+1(w)|+ |Hm+1(w)?Hm+2(Hm+1(w))| + + |Hk?1 ? ?Hm+1(w)?Hk(Hk?1 ? ?Hm+1(w))| < ?m 2m + ?m+1 2m+1...

  20. Melting Instantons, Domain Walls, and Large N

    E-Print Network [OSTI]

    H. B. Thacker

    2008-10-22T23:59:59.000Z

    Monte Carlo studies of $CP^{N-1}$ sigma models have shown that the structure of topological charge in these models undergoes a sharp transition at $N=N_c\\approx 4$. For $NN_c$ it is dominated by extended, thin, 1-dimensionally coherent membranes of topological charge, which can be interpreted as domain walls between discrete quasi-stable vacua. These vacua differ by a unit of background electric flux. The transition can be identified as the delocalization of topological charge, or "instanton melting," a phenomenon first suggested by Witten to resolve the conflict between instantons and large $N$ behavior. Implications for $QCD$ are discussed.

  1. Lattice gas simulations of replicating domains

    SciTech Connect (OSTI)

    Dawson, S.P.; Hasslacher, B.; Pearson, J.E.

    1993-12-31T23:59:59.000Z

    We use the lattice gas cellular automation (LGCA) developed to simulate a process of pattern-formation recently observed in reaction-diffusion systems. We study the reaction mechanism, which is an extension of the Selkov model for glycolytic oscillations. We are able to reproduce the self-replicating domains observed in this work. We use the LGCA simulation to estimate the smallest length-scale on which this process can occur under conditions encountered in the cell. These estimates are similar to those obtained for Turing patterns in the same setting.

  2. Detecting Networks Employing Algorithmically Generated Domain Names

    E-Print Network [OSTI]

    Ashwath Kumar Krishna Reddy

    2011-10-21T23:59:59.000Z

    . 15 0 0.02 0.04 0.06 0.08 0.1 0.12 0 1 2 3 4 5 6 7 8 9 a b c d e f g h i j k l m n o p q r s t u v w x y z Probability of occurrenc e Alphanumeric characters Malicious (Kraken) Malicious (Kwyjibo) Malicious (randomly generated... . . . . . . . . . . . . . . . . . . . 28 V RESULTS : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : 30 5.1 Per-domain analysis . . . . . . . . . . . . . . . . . . . . . . . . 30 5.1.1 Data set . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30 5.1.2 K...

  3. Neptunium Binding Kinetics with Arsenazo(III)

    SciTech Connect (OSTI)

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

    2014-08-01T23:59:59.000Z

    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.

  4. Cloning, purification and preliminary X-ray analysis of the C-terminal domain of Helicobacter pylori MotB

    SciTech Connect (OSTI)

    Roujeinikova, Anna, E-mail: anna.roujeinikova@manchester.ac.uk [Manchester Interdisciplinary Biocentre, Faculty of Life Sciences, University of Manchester, 131 Princess Street, Manchester M1 7DN (United Kingdom)

    2008-04-01T23:59:59.000Z

    The cloning, overexpression, purification, crystallization and preliminary X-ray diffraction analysis of a putative peptidoglycan-binding domain of H. pylori MotB, a stator component of the bacterial flagellar motor, are reported. The C-terminal domain of MotB (MotB-C) contains a putative peptidoglycan-binding motif and is believed to anchor the MotA/MotB stator unit of the bacterial flagellar motor to the cell wall. Crystals of Helicobacter pylori MotB-C (138 amino-acid residues) were obtained by the hanging-drop vapour-diffusion method using polyethylene glycol as a precipitant. These crystals belong to space group P2{sub 1}, with unit-cell parameters a = 50.8, b = 89.5, c = 66.3 , ? = 112.5. The crystals diffract X-rays to at least 1.6 resolution using a synchrotron-radiation source. Self-rotation function and Matthews coefficient calculations suggest that the asymmetric unit contains one tetramer with 222 point-group symmetry. The anomalous difference Patterson maps calculated for an ytterbium-derivative crystal using diffraction data at a wavelength of 1.38 showed significant peaks on the v = 1/2 Harker section, suggesting that ab initio phase information could be derived from the MAD data.

  5. Cancer-associated p53 tetramerization domain mutants: quantitative analysis reveals a low threshold for tumor suppressor inactivation

    SciTech Connect (OSTI)

    Kamada, R.; Anderson, C.; Nomura, T.; Sakaguchi, K.

    2011-01-07T23:59:59.000Z

    The tumor suppressor p53, a 393-amino acid transcription factor, induces cell cycle arrest and apoptosis in response to genotoxic stress. Its inactivation via the mutation of its gene is a key step in tumor progression, and tetramer formation is critical for p53 post-translational modification and its ability to activate or repress the transcription of target genes vital in inhibiting tumor growth. About 50% of human tumors have TP53 gene mutations; most are missense ones that presumably lower the tumor suppressor activity of p53. In this study, we explored the effects of known tumor-derived missense mutations on the stability and oligomeric structure of p53; our comprehensive, quantitative analyses encompassed the tetramerization domain peptides representing 49 such substitutions in humans. Their effects on tetrameric structure were broad, and the stability of the mutant peptides varied widely ({Delta}T{sub m} = 4.8 {approx} -46.8 C). Because formation of a tetrameric structure is critical for protein-protein interactions, DNA binding, and the post-translational modification of p53, a small destabilization of the tetrameric structure could result in dysfunction of tumor suppressor activity. We suggest that the threshold for loss of tumor suppressor activity in terms of the disruption of the tetrameric structure of p53 could be extremely low. However, other properties of the tetramerization domain, such as electrostatic surface potential and its ability to bind partner proteins, also may be important.

  6. The mitochondrial ND1 m.3337G>A mutation associated to multiple mitochondrial DNA deletions in a patient with Wolfram syndrome and cardiomyopathy

    SciTech Connect (OSTI)

    Mezghani, Najla [Laboratoire de Genetique Moleculaire Humaine, Faculte de Medecine de Sfax, Universite de Sfax (Tunisia)] [Laboratoire de Genetique Moleculaire Humaine, Faculte de Medecine de Sfax, Universite de Sfax (Tunisia); Mnif, Mouna [Service d'endocrinologie, C.H.U. Habib Bourguiba de Sfax (Tunisia)] [Service d'endocrinologie, C.H.U. Habib Bourguiba de Sfax (Tunisia); Mkaouar-Rebai, Emna, E-mail: emna_mkaouar@mail2world.com [Laboratoire de Genetique Moleculaire Humaine, Faculte de Medecine de Sfax, Universite de Sfax (Tunisia)] [Laboratoire de Genetique Moleculaire Humaine, Faculte de Medecine de Sfax, Universite de Sfax (Tunisia); Kallel, Nozha [Service d'endocrinologie, C.H.U. Habib Bourguiba de Sfax (Tunisia)] [Service d'endocrinologie, C.H.U. Habib Bourguiba de Sfax (Tunisia); Salem, Ikhlass Haj [Laboratoire de Genetique Moleculaire Humaine, Faculte de Medecine de Sfax, Universite de Sfax (Tunisia)] [Laboratoire de Genetique Moleculaire Humaine, Faculte de Medecine de Sfax, Universite de Sfax (Tunisia); Charfi, Nadia; Abid, Mohamed [Service d'endocrinologie, C.H.U. Habib Bourguiba de Sfax (Tunisia)] [Service d'endocrinologie, C.H.U. Habib Bourguiba de Sfax (Tunisia); Fakhfakh, Faiza [Laboratoire de Genetique Moleculaire Humaine, Faculte de Medecine de Sfax, Universite de Sfax (Tunisia)] [Laboratoire de Genetique Moleculaire Humaine, Faculte de Medecine de Sfax, Universite de Sfax (Tunisia)

    2011-07-29T23:59:59.000Z

    Highlights: {yields} We reported a patient with Wolfram syndrome and dilated cardiomyopathy. {yields} We detected the ND1 mitochondrial m.3337G>A mutation in 3 tested tissues (blood leukocytes, buccal mucosa and skeletal muscle). {yields} Long-range PCR amplification revealed the presence of multiple mitochondrial deletions in the skeletal muscle. {yields} The deletions remove several tRNA and protein-coding genes. -- Abstract: Wolfram syndrome (WFS) is a rare hereditary disorder also known as DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness). It is a heterogeneous disease and full characterization of all clinical and biological features of this disorder is difficult. The wide spectrum of clinical expression, affecting several organs and tissues, and the similarity in phenotype between patients with Wolfram syndrome and those with certain types of respiratory chain diseases suggests mitochondrial DNA (mtDNA) involvement in Wolfram syndrome patients. We report a Tunisian patient with clinical features of moderate Wolfram syndrome including diabetes, dilated cardiomyopathy and neurological complications. The results showed the presence of the mitochondrial ND1 m.3337G>A mutation in almost homoplasmic form in 3 tested tissues of the proband (blood leukocytes, buccal mucosa and skeletal muscle). In addition, the long-range PCR amplifications revealed the presence of multiple deletions of the mitochondrial DNA extracted from the patient's skeletal muscle removing several tRNA and protein-coding genes. Our study reported a Tunisian patient with clinical features of moderate Wolfram syndrome associated with cardiomyopathy, in whom we detected the ND1 m.3337G>A mutation with mitochondrial multiple deletions.

  7. Engineering Deletions in the Mg1-Pk1 Gene Cluster of Streptomyces sp. Mg1 to Abolish Production of the Mg1-Pk1 Metabolite

    E-Print Network [OSTI]

    Moisan, Sabrina

    2013-09-25T23:59:59.000Z

    and inserted into the mass spectrometer. The spectrometer is programmed to collect spectra at predefined points in an x-y grid across the sample. The spectra can then be used to construct colorized images.3 Some metabolites, such as chalcomycin produced... ENGINEERING DELETIONS IN THE MG1-PK1 GENE CLUSTER OF STREPTOMYCES sp. MG1 TO ABOLISH PRODUCTION OF THE MG1- PK1 METABOLITE An Undergraduate Research Scholars Thesis by SABRINA MOISAN Submitted to Honors and Undergraduate Research...

  8. Hydrogen Bonding Penalty upon Ligand Binding Hongtao Zhao, Danzhi Huang*

    E-Print Network [OSTI]

    Caflisch, Amedeo

    Hydrogen Bonding Penalty upon Ligand Binding Hongtao Zhao, Danzhi Huang* Department of Biochemistry, University of Zurich, Zurich, Switzerland Abstract Ligand binding involves breakage of hydrogen bonds with water molecules and formation of new hydrogen bonds between protein and ligand. In this work, the change

  9. The DNA binding activity of p53 displays reactiondiffusion kinetics

    E-Print Network [OSTI]

    Hinow, Peter

    The DNA binding activity of p53 displays reactiondiffusion kinetics 26th Southeastern 37240 The DNA binding activity of p53 displays reactiondiffusion kinetics p. 1/2 #12;Collaborators, Vanderbilt University Emmanuele DiBenedetto, PhD, Department of Mathematics, Vanderbilt University The DNA

  10. Unexpected Nondissociative Binding of N2O on Oxygen Vacancies...

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

    Nondissociative Binding of N2O on Oxygen Vacancies on a Rutile TiO2(110)-11 . Unexpected Nondissociative Binding of N2O on Oxygen Vacancies on a Rutile TiO2(110)-11 ....

  11. news and views nucleotide binds to the polymerase and

    E-Print Network [OSTI]

    Schedl, Paul

    news and views nucleotide binds to the polymerase and before it is incorporated into DNA. Recent structures of several structurally diverse DNA polymerases complexed to DNA and nucleotide substrates have shown that their active sites adopt a closed conforma- tion upon binding to the correct nucleotide12

  12. WHERE MULTIFUNCTIONAL DNA REPAIR PROTEINS MEET: MAPPING THE INTERACTION DOMAINS BETWEEN XPG AND WRN

    SciTech Connect (OSTI)

    Rangaraj, K.; Cooper, P.K.; Trego, K.S.

    2009-01-01T23:59:59.000Z

    The rapid recognition and repair of DNA damage is essential for the maintenance of genomic integrity and cellular survival. Multiple complex and interconnected DNA damage responses exist within cells to preserve the human genome, and these repair pathways are carried out by a specifi c interplay of protein-protein interactions. Thus a failure in the coordination of these processes, perhaps brought about by a breakdown in any one multifunctional repair protein, can lead to genomic instability, developmental and immunological abnormalities, cancer and premature aging. This study demonstrates a novel interaction between two such repair proteins, Xeroderma pigmentosum group G protein (XPG) and Werner syndrome helicase (WRN), that are both highly pleiotropic and associated with inherited genetic disorders when mutated. XPG is a structure-specifi c endonuclease required for the repair of UV-damaged DNA by nucleotide excision repair (NER), and mutations in XPG result in the diseases Xeroderma pigmentosum (XP) and Cockayne syndrome (CS). A loss of XPG incision activity results in XP, whereas a loss of non-enzymatic function(s) of XPG causes CS. WRN is a multifunctional protein involved in double-strand break repair (DSBR), and consists of 35 DNA-dependent helicase, 35 exonuclease, and single-strand DNA annealing activities. Nonfunctional WRN protein leads to Werner syndrome, a premature aging disorder with increased cancer incidence. Far Western analysis was used to map the interacting domains between XPG and WRN by denaturing gel electrophoresis, which separated purifi ed full length and recombinant XPG and WRN deletion constructs, based primarily upon the length of each polypeptide. Specifi c interacting domains were visualized when probed with the secondary protein of interest which was then detected by traditional Western analysis using the antibody of the secondary protein. The interaction between XPG and WRN was mapped to the C-terminal region of XPG as well as the C-terminal region of WRN. The physical interaction between XPG and WRN links NER, (made evident by the disease XP) with DSBR, which imparts additional knowledge of the overlapping nature of these two proteins and the previously distinct DNA repair pathways they are associated with. Since genomic integrity is constantly threatened by both endogenous and exogenous (internal and external) damage, understanding the roles of these proteins in coordinating DNA repair processes with replication will signifi cantly further understanding how defects instigate physiological consequences in response to various DNA damaging sources. This ultimately contributes to our understanding of cancer and premature aging.

  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. (NWU); (Stanford-MED)

    2014-10-02T23:59:59.000Z

    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. Fold of the conserved DTC domain in deltex proteins

    SciTech Connect (OSTI)

    Obiero, Josiah; Walker, John R.; Dhe-Paganon, Sirano (Toronto)

    2012-04-30T23:59:59.000Z

    Human Deltex 3-like (DTX3L) is a member of the Deltex family of proteins. Initially identified as a B-lymphoma and BAL-associated protein, DTX3L is an E3 ligase that regulates subcellular localization of its partner protein, BAL, by a dynamic nucleocytoplasmic trafficking mechanism. Unlike other members of the Deltex family of proteins, DTX3L lacks the highly basic N-terminal motif and the central proline-rich motif present in other Deltex proteins, and instead contains other unique N-terminal domains. The C-terminal domains are, however, homologous with other members of the Deltex family of proteins; these include a RING domain and a previously unidentified C-terminal domain. In this study, we report the high-resolution crystal structure of this previously uncharacterized C-terminal domain of human DTX3L, which we term the Deltex C-terminal domain.

  15. The Crystal Structure of the Active Form of the C-Terminal Kinase Domain of Mitogen- and Stress-Activated Protein Kinase 1

    SciTech Connect (OSTI)

    Malakhova, Margarita; D'Angelo, Igor; Kim, Hong-Gyum; Kurinov, Igor; Bode, Ann M.; Dong, Zigang (Cornell); (UMM)

    2010-06-25T23:59:59.000Z

    Mitogen- and stress-activated protein kinase 1 (MSK1) is a growth-factor-stimulated serine/threonine kinase that is involved in gene transcription regulation and proinflammatory cytokine stimulation. MSK1 is a dual kinase possessing two nonidentical protein kinase domains in one polypeptide. We present the active conformation of the crystal structures of its C-terminal kinase domain in apo form and in complex with a nonhydrolyzable ATP analogue at 2.0 {angstrom} and 2.5 {angstrom} resolutions, respectively. Structural analysis revealed substantial differences in the contacts formed by the C-terminal helix, which is responsible for the inactivity of other autoinhibited kinases. In the C-terminal kinase domain of MSK1, the C-terminal {alpha}L-helix is located in the surface groove, but forms no hydrogen bonds with the substrate-binding loop or nearby helices, and does not interfere with the protein's autophosphorylation activity. Mutational analysis confirmed that the {alpha}L-helix is inherently nonautoinhibitory. Overexpression of the single C-terminal kinase domain in JB6 cells resulted in tumor-promoter-induced neoplastic transformation in a manner similar to that induced by the full-length MSK1 protein. The overall results suggest that the C-terminal kinase domain of MSK1 is regulated by a novel {alpha}L-helix-independent mechanism, suggesting that a diverse mechanism of autoinhibition and activation might be adopted by members of a closely related protein kinase family.

  16. Birefringence insensitive optical coherence domain reflectometry system

    DOE Patents [OSTI]

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

    2002-01-01T23:59:59.000Z

    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.

  17. Apo calmodulin binding to the L-type voltage-gated calcium channel Ca{sub v}1.2 IQ peptide

    SciTech Connect (OSTI)

    Lian Luyun [School of Biological Sciences, University of Liverpool, P.O. Box 147, Liverpool L69 7ZB (United Kingdom)]. E-mail: lu-yun.lian@liverpool.ac.uk; Myatt, Daniel [School of Medicine, Cardiovascular and Endocrine Sciences, University of Manchester, Manchester M13 9NT (United Kingdom); Kitmitto, Ashraf [School of Medicine, Cardiovascular and Endocrine Sciences, University of Manchester, Manchester M13 9NT (United Kingdom)]. E-mail: ashraf.kitmitto@manchester.ac.uk

    2007-02-16T23:59:59.000Z

    The influx of calcium through the L-type voltage-gated calcium channels (LTCCs) is the trigger for the process of calcium-induced calcium release (CICR) from the sarcoplasmic recticulum, an essential step for cardiac contraction. There are two feedback mechanisms that regulate LTCC activity: calcium-dependent inactivation (CDI) and calcium-dependent facilitation (CDF), both of which are mediated by calmodulin (CaM) binding. The IQ domain (aa 1645-1668) housed within the cytoplasmic domain of the LTCC Ca{sub v}1.2 subunit has been shown to bind both calcium-loaded (Ca{sup 2+}CaM ) and calcium-free CaM (apoCaM). Here, we provide new data for the structural basis for the interaction of apoCaM with the IQ peptide using NMR, revealing that the apoCaM C-lobe residues are most significantly perturbed upon complex formation. In addition, we have employed transmission electron microscopy of purified LTCC complexes which shows that both apoCaM and Ca{sup 2+}CaM can bind to the intact channel.

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

    Open Energy Info (EERE)

    GEOTHERMAL ENERGYGeothermal Home Exploration Activity: Time-Domain Electromagnetics At Glass Mountain Area (Cumming And Mackie, 2007) Exploration Activity Details Location Glass...

  19. apolipoprotein domain derived: Topics by E-print Network

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

    of humans and computers, domain spe- cific APIs contain a considerable amount Ratiu, Daniel 265 www.mdpi.comjournalijms Proteolytic Cleavage of Apolipoprotein E4 as the...

  20. antiphase domain boundaries: Topics by E-print Network

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

    Summary: Absorbing Boundary Condition, Domain Decomposition and Hydrodynamic Wave Model O. Wilk Introduction. appli. (wave equation) Num. appli. (hydro. wave model)...

  1. Quantifying the mechanisms of domain gain in animal proteins

    E-Print Network [OSTI]

    Buljan, Marija; Frankish, Adam; Bateman, Alex

    2010-07-15T23:59:59.000Z

    , if a domain gain is reported in the genomes with better quality annotations it could be that in the genomes of lower quality the domain is missing only due to incomplete annotation. To investigate the possible extent of errors introduced by the first... by this error. Namely, domain gains that occurred in the human lineage after the divergence of vertebrates (121 reported domain gain events) can have on one side well studied genomes as human and mouse and on the other side, as an outgroup, lower quality...

  2. Time-Domain Electromagnetics At Neal Hot Springs Geothermal Area...

    Open Energy Info (EERE)

    Activity: Time-Domain Electromagnetics At Neal Hot Springs Geothermal Area (Colorado School of Mines and Imperial College London, 2011) Exploration Activity Details Location Neal...

  3. Abstract Domains of Affine Relations MATT ELDER, University of Wisconsin

    E-Print Network [OSTI]

    Reps, Thomas W.

    modulo 2w, for some machine-integer width w). We show that the abstract domains of M¨uller-Olm/Seidl (MOS

  4. Controlled Source Frequency-Domain Electromagnetics At Neal Hot...

    Open Energy Info (EERE)

    Source Frequency-Domain Electromagnetics Activity Date 2011 - 2011 Usefulness useful DOE-funding Unknown Exploration Basis Electromagnetic surveys were conducted to gain a better...

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

    Open Energy Info (EERE)

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

  6. Untangling spider silk evolution with spidroin terminal domains.

    E-Print Network [OSTI]

    Garb, Jessica E; Ayoub, Nadia A; Hayashi, Cheryl Y

    2010-01-01T23:59:59.000Z

    evolution with spidroin terminal domains. BMC Evolutionaryconservation in the C-terminal region of spider silkAdditional file 1: N-terminal alignment, top line shows

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

    Open Energy Info (EERE)

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

  8. 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...

  9. Enhancement of disoriented chiral condensate domains with friction

    E-Print Network [OSTI]

    A. K. Chaudhuri

    1999-04-08T23:59:59.000Z

    We investigate the effect of friction on domain formation in disoriented chiral condensate. Including a friction term, we solve the equation of motion of the linear sigma model fields, in the Hartree approximation. With boost-invariance and cylinderical symmetry, irrespective of friction, on average, we donot find any indication of domain like formation with quenched initial condition. However, with or without friction, some events can be found with large instabilities, indicating possible DCC domain formation in those events. With friction time scale during which instabilities grows increases. Correspondingly, with friction, it is possible to obtain large sized domains in some particular events.

  10. Ultrabroadband coherence-domain imaging using parametric downconversion and

    E-Print Network [OSTI]

    Teich, Malvin C.

    Ultrabroadband coherence-domain imaging using parametric downconversion and superconducting single lithium tantalate (chirped-PPSLT) structure, in conjunction with a niobium nitride superconducting single

  11. 'Escherichia Coli' MutS Tetramerization Domain Structure Reveals That Stable Dimers But Not Tetramers are Essential for DNA Mismatch Repair in Vivo

    SciTech Connect (OSTI)

    Mendillo, M.L.; Putnam, C.D.; Kolodner, R.D.; /UC, San Diego

    2007-07-10T23:59:59.000Z

    The E. coli mispair binding protein MutS forms dimers and tetramers in vitro, although the functional form in vivo is under debate. Here we demonstrate that the MutS tetramer is extended in solution using small angle x-ray scattering (SAXS) and the crystal structure of the C-terminal 34 amino acids of MutS containing the tetramer-forming domain fused to maltose binding protein (MBP). Wild-type C-terminal MBP fusions formed tetramers and could bind MutS and MutS-MutL-DNA complexes. In contrast, Asp835Arg and Arg840Glu mutations predicted to disrupt tetrameric interactions only allowed dimerization of MBP. A chromosomal MutS truncation mutation eliminating the dimerization/tetramerization domain eliminated mismatch repair, whereas the tetramer-disrupting MutS Asp835Arg and Arg840Glu mutations only modestly affected MutS function. These results demonstrate that dimerization but not tetramerization of the MutS C- terminus is essential for mismatch repair.

  12. 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. (Einstein); (SLAC); (Rockefeller); (UCSF); (Lilly)

    2012-10-23T23:59:59.000Z

    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.

  13. X-ray Crystallographic Studies of Substrate Binding to Aristolochene Synthase Suggest a Metal Ion Binding Sequence for Catalysis

    SciTech Connect (OSTI)

    Shishova,E.; Yu, F.; Miller, D.; Faraldos, J.; Zhao, Y.; Coates, R.; Allemann, R.; Cane, D.; Christianson, D.

    2008-01-01T23:59:59.000Z

    The universal sesquiterpene precursor, farnesyl diphosphate (FPP), is cyclized in an Mg2+-dependent reaction catalyzed by the tetrameric aristolochene synthase from Aspergillus terreus to form the bicyclic hydrocarbon aristolochene and a pyrophosphate anion (PPi) coproduct. The 2.1- Angstroms resolution crystal structure determined from crystals soaked with FPP reveals the binding of intact FPP to monomers A-C, and the binding of PPi and Mg2+B to monomer D. The 1.89- Angstroms resolution structure of the complex with 2-fluorofarnesyl diphosphate (2F-FPP) reveals 2F-FPP binding to all subunits of the tetramer, with Mg2+Baccompanying the binding of this analogue only in monomer D. All monomers adopt open activesite conformations in these complexes, but slight structural changes in monomers C and D of each complex reflect the very initial stages of a conformational transition to the closed state. Finally, the 2.4- Angstroms resolution structure of the complex with 12,13-difluorofarnesyl diphosphate (DF-FPP) reveals the binding of intact DF-FPP to monomers A-C in the open conformation and the binding of PPi, Mg2+B, and Mg2+C to monomer D in a predominantly closed conformation. Taken together, these structures provide 12 independent 'snapshots' of substrate or product complexes that suggest a possible sequence for metal ion binding and conformational changes required for catalysis.

  14. Efficient Pruning of Operators in Planning Domains Anders Jonsson

    E-Print Network [OSTI]

    Jonsson, Anders

    of individual state variables and performs search in the graphs to identify re­ dundant operators. We prove.jonsson@upf.edu Abstract. Many recent successful planners use domain­independent heuristics to speed up the search domains demonstrate that our algorithm can reduce the number of operators as well as speed up search. 1

  15. Efficient Pruning of Operators in Planning Domains Anders Jonsson

    E-Print Network [OSTI]

    Jonsson, Anders

    of individual state variables and performs search in the graphs to identify re- dundant operators. We prove.jonsson@upf.edu Abstract. Many recent successful planners use domain-independent heuristics to speed up the search domains demonstrate that our algorithm can reduce the number of operators as well as speed up search. 1

  16. NExpTime-complete Description Logics with Concrete Domains

    E-Print Network [OSTI]

    Baader, Franz

    that reasoning with the concrete do- main D (i.e., testing the satis#12;ability of #12;nite conjunctionsChapter 1 NExpTime-complete Description Logics with Concrete Domains Carsten Lutz Abstract. Description Logics (DLs) incorporating concrete domains are useful formalisms for integrated reasoning about

  17. Vector dark domain wall solitons in a fiber ring laser

    E-Print Network [OSTI]

    H. Zhang; D. Y. Tang; L. M. Zhao; R. J. Knize

    2009-10-15T23:59:59.000Z

    We observe a novel type of vector dark soliton in a fiber ring laser. The vector dark soliton consists of stable localized structures separating the two orthogonal linear polarization eigenstates of the laser emission and is visible only when the total laser emission is measured. Moreover, polarization domain splitting and moving polarization domain walls (PDWs) were also experimentally observed.

  18. WELL-CENTERED OVERRINGS OF AN INTEGRAL DOMAIN

    E-Print Network [OSTI]

    Heinzer, William

    WELL-CENTERED OVERRINGS OF AN INTEGRAL DOMAIN is a localization of A if and only if B is flat and well-centered over A. If the integral clo* *sure.3 that a simple flat well-centered overring of an integral domain A is a localization of A. If the integral

  19. NExpTime-complete Description Logics with Concrete Domains

    E-Print Network [OSTI]

    Baader, Franz

    NExpTime-complete Description Logics with Concrete Domains Carsten Lutz LuFG Theoretical Computer Science RWTH Aachen, Germany lutz@cs.rwth-aachen.de Abstract. Concrete domains are an extension \\concrete properties" of objects such as sizes, weights, and durations. It is known that reasoning with ALC

  20. LNG FEM: Graded Meshes on Domains of Polygonal Structures

    E-Print Network [OSTI]

    Nistor, Victor

    LNG FEM: Graded Meshes on Domains of Polygonal Structures Hengguang Li and Victor Nistor Abstract. We develop LNG FEM, a software package for graded mesh generation and for solving elliptic equations. LNG FEM gen- erates user-specified graded meshes on arbitrary 2D domains with straight edges

  1. Measuring Availability in the Domain Name System Casey Deccio

    E-Print Network [OSTI]

    California at Davis, University of

    Measuring Availability in the Domain Name System Casey Deccio Sandia National Laboratories ctdecci to Inter- net functionality. The availability of a domain name refers to its ability to be resolved correctly. We develop a model for server dependencies that is used as a basis for measuring availability. We

  2. Stripe Domain-Structures in a Thin Ferromagnetic Film

    E-Print Network [OSTI]

    KASHUBA, AB; Pokrovsky, Valery L.

    1993-01-01T23:59:59.000Z

    We present a theory of the stripe domain structure in a thin ferromagnetic film with single-ion easy-axis magnetic anisotropy and long-range dipole interactions, for a wide range of temperatures and applied magnetic field. The domains exist...

  3. ORIGINAL ARTICLE Single ferroelectric-domain photovoltaic switch based

    E-Print Network [OSTI]

    Jo, Moon-Ho

    ORIGINAL ARTICLE Single ferroelectric-domain photovoltaic switch based on lateral BiFeO3 cells Ji serves as a basis for solid-state memory. This phenomenon can also yield an interesting photovoltaic imposed by the ferroelectric polarization vectors. Here, we demonstrate a single-domain photovoltaic

  4. Important Cognitive Components of Domain-Specific Search Knowledge

    E-Print Network [OSTI]

    Bhavnani, Suresh K.

    the subject-specific terms to enter in a query. For example, many university students often buy electronicImportant Cognitive Components of Domain-Specific Search Knowledge Suresh K. Bhavnani School Many users have acquired a sophisticated understanding of searching the Web in specific domains

  5. Induction, Domains, Calculi: Strachey's Contributions to ProgrammingLanguage

    E-Print Network [OSTI]

    Schmidt, David A.

    Induction, Domains, Calculi: Strachey's Contributions to ProgrammingLanguage Engineering David A's contributions---inductive defini tion of semantics, semanticdomain definitions, and calculi for semantic description---are presented, and their consequences on languages research are described. Strachey's impact

  6. Expanded polyglutamine domain possesses nuclear export activity which modulates subcellular

    E-Print Network [OSTI]

    Higgins, Darren

    experiments, were ana- lyzed. Mammalian cell culture HEK293 cells were cultured at 378C with 5% CO2 in high,16). To investigate the nuclear transport property of expanded polyQ domain per se, we initially took advantage then focused on elucidating the nuclear export property of an expanded polyQ domain and its associated

  7. Knowledge Transformation for Cross-Domain Sentiment Classification

    E-Print Network [OSTI]

    Li, Tao

    Knowledge Transformation for Cross-Domain Sentiment Classification Tao Li School of Computer With the explosion of user-generated web2.0 content in the form of blogs, wikis and discussion forums, the Internet domain, thereby build- ing high-quality sentiment models without manual effort? We outline a novel

  8. CONSTRUCTIVE DOMAIN THEORY AS A BRANCH OF INTUITIONISTIC POINTFREE TOPOLOGY

    E-Print Network [OSTI]

    Valentini, Silvio

    in early 80's proposed in [Scott 81a], [Scott 82] and [Scott 81b] more intuitive presentations of domains Valentini, Paolo Virgili Dipartimento di Matematica Pura e Applicata Universit`a di Padova Abstract theory. Technically, they form a category which is equivalent to the category of Scott domains

  9. Catheter guided by optical coherence domain reflectometry

    DOE Patents [OSTI]

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

    2002-01-01T23:59:59.000Z

    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.

  10. Data challenges of time domain astronomy

    E-Print Network [OSTI]

    Graham, Matthew J; Mahabal, Ashish; Donalek, Ciro; Drake, Andrew; Longo, Giuseppe

    2012-01-01T23:59:59.000Z

    Astronomy has been at the forefront of the development of the techniques and methodologies of data intensive science for over a decade with large sky surveys and distributed efforts such as the Virtual Observatory. However, it faces a new data deluge with the next generation of synoptic sky surveys which are opening up the time domain for discovery and exploration. This brings both new scientific opportunities and fresh challenges, in terms of data rates from robotic telescopes and exponential complexity in linked data, but also for data mining algorithms used in classification and decision making. In this paper, we describe how an informatics-based approach-part of the so-called "fourth paradigm" of scientific discovery-is emerging to deal with these. We review our experiences with the Palomar-Quest and Catalina Real-Time Transient Sky Surveys; in particular, addressing the issue of the heterogeneity of data associated with transient astronomical events (and other sensor networks) and how to manage and analy...

  11. Dual-domain lateral shearing interferometer

    DOE Patents [OSTI]

    Naulleau, Patrick P.; Goldberg, Kenneth Alan

    2004-03-16T23:59:59.000Z

    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.

  12. DB-PABP: a database of polyanion-binding proteins

    E-Print Network [OSTI]

    Fang, Jianwen; Dong, Yinghua; Slamat-Miller, Nazila; Middaugh, C. Russell

    2007-10-04T23:59:59.000Z

    The interactions between polyanions (PAs) and polyanion-binding proteins (PABPs) have been found to play significant roles in many essential biological processes including intracellular organization, transport and protein folding. Furthermore, many...

  13. Research paper Drug diffusion and binding in ionizable interpenetrating networks

    E-Print Network [OSTI]

    Peppas, Nicholas A.

    Research paper Drug diffusion and binding in ionizable interpenetrating networks from poly) (PVA), poly(acrylic acid) (PAA), and their interpenetrating networks (IPNs) were prepared using by measuring their equilibrium polymer volume fraction, equilibrium swelling ratio, and mesh size. Drug

  14. Original article Distribution of endogenous retinoids, retinoid binding

    E-Print Network [OSTI]

    Paris-Sud XI, Universit de

    of specific retinoid-binding proteins was investigated; these are involved in vitamin A transport, metabolism is induced by a concentration gradient (high posteri- orly) of all-trans-RA along the anterior-p

  15. Understanding regulation of mRNA by RNA binding proteins

    E-Print Network [OSTI]

    Robertson, Alexander De Jong

    2014-01-01T23:59:59.000Z

    Posttranscriptional regulation of mRNA by RNA-binding proteins plays key roles in regulating the transcriptome over the course of development, between tissues and in disease states. The specific interactions between mRNA ...

  16. acid inhibitor binding: Topics by E-print Network

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

    of correctly predicted inter- face residues in actual interface residues Zhou, Yaoqi 162 Sm-like protein Hfq: Location of the ATP-binding site and the effect of ATP on HfqRNA...

  17. atp binding protein: Topics by E-print Network

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

    corroborate asymmetry of catalysis in F0F1-ATP synthase. Zarrabi, Nawid; Diez, Manuel; Graeber, Peter; Wrachtrup, Joerg; Boersch, Michael 2007-01-01 408 Interplay of pH and Binding...

  18. Metal binding proteins, recombinant host cells and methods

    DOE Patents [OSTI]

    Summers, Anne O.; Caguiat, Jonathan J.

    2004-06-15T23:59:59.000Z

    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.

  19. angiotensin binding site: Topics by E-print Network

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

    Ser-142 (14). Ser-129 is believed to be a substrate for glycogen synthase kinase 3 Brownfield, Mark S. 55 Similarity Analysis of Protein Binding Sites: A Generalization of the...

  20. antigen binding site: Topics by E-print Network

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

    Ser-142 (14). Ser-129 is believed to be a substrate for glycogen synthase kinase 3 Brownfield, Mark S. 69 Similarity Analysis of Protein Binding Sites: A Generalization of the...

  1. alcohol binding sites: Topics by E-print Network

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

    Ser-142 (14). Ser-129 is believed to be a substrate for glycogen synthase kinase 3 Brownfield, Mark S. 56 Similarity Analysis of Protein Binding Sites: A Generalization of the...

  2. albumin binding sites: Topics by E-print Network

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

    Ser-142 (14). Ser-129 is believed to be a substrate for glycogen synthase kinase 3 Brownfield, Mark S. 54 Similarity Analysis of Protein Binding Sites: A Generalization of the...

  3. anesthetic binding site: Topics by E-print Network

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

    Ser-142 (14). Ser-129 is believed to be a substrate for glycogen synthase kinase 3 Brownfield, Mark S. 57 Similarity Analysis of Protein Binding Sites: A Generalization of the...

  4. acid binding sites: Topics by E-print Network

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

    Ser-142 (14). Ser-129 is believed to be a substrate for glycogen synthase kinase 3 Brownfield, Mark S. 82 Similarity Analysis of Protein Binding Sites: A Generalization of the...

  5. aml-1 binding site: Topics by E-print Network

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

    Ser-142 (14). Ser-129 is believed to be a substrate for glycogen synthase kinase 3 Brownfield, Mark S. 55 Similarity Analysis of Protein Binding Sites: A Generalization of the...

  6. affinity binding sites: Topics by E-print Network

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

    Ser-142 (14). Ser-129 is believed to be a substrate for glycogen synthase kinase 3 Brownfield, Mark S. 112 Similarity Analysis of Protein Binding Sites: A Generalization of the...

  7. antagonist binding sites: Topics by E-print Network

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

    Ser-142 (14). Ser-129 is believed to be a substrate for glycogen synthase kinase 3 Brownfield, Mark S. 58 Similarity Analysis of Protein Binding Sites: A Generalization of the...

  8. alcohol binding site: Topics by E-print Network

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

    Ser-142 (14). Ser-129 is believed to be a substrate for glycogen synthase kinase 3 Brownfield, Mark S. 56 Similarity Analysis of Protein Binding Sites: A Generalization of the...

  9. androgen binding protein: Topics by E-print Network

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

    Ser-142 (14). Ser-129 is believed to be a substrate for glycogen synthase kinase 3 Brownfield, Mark S. 135 A High-Throughput Solid-Phase Microplate Protein-Binding Assay to...

  10. antidepressant binding site: Topics by E-print Network

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

    Ser-142 (14). Ser-129 is believed to be a substrate for glycogen synthase kinase 3 Brownfield, Mark S. 55 Similarity Analysis of Protein Binding Sites: A Generalization of the...

  11. antibody binding site: Topics by E-print Network

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

    Ser-142 (14). Ser-129 is believed to be a substrate for glycogen synthase kinase 3 Brownfield, Mark S. 75 Binding of HIV-1 gp41-Directed Neutralizing and Non-Neutralizing...

  12. autoantibody binding site: Topics by E-print Network

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

    Ser-142 (14). Ser-129 is believed to be a substrate for glycogen synthase kinase 3 Brownfield, Mark S. 56 Similarity Analysis of Protein Binding Sites: A Generalization of the...

  13. atp binding site: Topics by E-print Network

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

    Ser-142 (14). Ser-129 is believed to be a substrate for glycogen synthase kinase 3 Brownfield, Mark S. 90 Similarity Analysis of Protein Binding Sites: A Generalization of the...

  14. auxin binding protein: Topics by E-print Network

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

    Ser-142 (14). Ser-129 is believed to be a substrate for glycogen synthase kinase 3 Brownfield, Mark S. 150 A High-Throughput Solid-Phase Microplate Protein-Binding Assay to...

  15. acid binding site: Topics by E-print Network

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

    Ser-142 (14). Ser-129 is believed to be a substrate for glycogen synthase kinase 3 Brownfield, Mark S. 82 Similarity Analysis of Protein Binding Sites: A Generalization of the...

  16. androgen binding sites: Topics by E-print Network

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

    Ser-142 (14). Ser-129 is believed to be a substrate for glycogen synthase kinase 3 Brownfield, Mark S. 55 Similarity Analysis of Protein Binding Sites: A Generalization of the...

  17. affinity binding site: Topics by E-print Network

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

    Ser-142 (14). Ser-129 is believed to be a substrate for glycogen synthase kinase 3 Brownfield, Mark S. 112 Similarity Analysis of Protein Binding Sites: A Generalization of the...

  18. a1 binding site: Topics by E-print Network

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

    Ser-142 (14). Ser-129 is believed to be a substrate for glycogen synthase kinase 3 Brownfield, Mark S. 59 Similarity Analysis of Protein Binding Sites: A Generalization of the...

  19. amp binding proteins: Topics by E-print Network

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

    Ser-142 (14). Ser-129 is believed to be a substrate for glycogen synthase kinase 3 Brownfield, Mark S. 4 Volume 159, number 1,2 FEBS 0638 August 1983 Specific DNA binding of the...

  20. agonist binding site: Topics by E-print Network

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

    Ser-142 (14). Ser-129 is believed to be a substrate for glycogen synthase kinase 3 Brownfield, Mark S. 62 Similarity Analysis of Protein Binding Sites: A Generalization of the...

  1. assisted binding site: Topics by E-print Network

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

    Ser-142 (14). Ser-129 is believed to be a substrate for glycogen synthase kinase 3 Brownfield, Mark S. 54 Similarity Analysis of Protein Binding Sites: A Generalization of the...

  2. allosteric binding sites: Topics by E-print Network

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

    Ser-142 (14). Ser-129 is believed to be a substrate for glycogen synthase kinase 3 Brownfield, Mark S. 68 Similarity Analysis of Protein Binding Sites: A Generalization of the...

  3. allosteric binding site: Topics by E-print Network

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

    Ser-142 (14). Ser-129 is believed to be a substrate for glycogen synthase kinase 3 Brownfield, Mark S. 68 Similarity Analysis of Protein Binding Sites: A Generalization of the...

  4. activator inhibitor-1 binding: Topics by E-print Network

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

    Ser-142 (14). Ser-129 is believed to be a substrate for glycogen synthase kinase 3 Brownfield, Mark S. 147 Stress modulation of visuomotor binding CiteSeer Summary: The primate...

  5. Structure of a Glomulin-RBX1-CUL1 Complex: Inhibition of a RING E3 Ligase through Masking of Its E2-Binding Surface

    SciTech Connect (OSTI)

    Duda, David M.; Olszewski, Jennifer L.; Tron, Adriana E.; Hammel, Michal; Lambert, Lester J.; Waddell, M. Brett; Mittag, Tanja; DeCaprio, James A.; Schulman, Brenda A. (BWH); (LBNL); (SJCH); (DFCI)

    2012-11-01T23:59:59.000Z

    The approximately 300 human cullin-RING ligases (CRLs) are multisubunit E3s in which a RING protein, either RBX1 or RBX2, recruits an E2 to catalyze ubiquitination. RBX1-containing CRLs also can bind Glomulin (GLMN), which binds RBX1's RING domain, regulates the RBX1-CUL1-containing SCF{sup FBW7} complex, and is disrupted in the disease Glomuvenous Malformation. Here we report the crystal structure of a complex between GLMN, RBX1, and a fragment of CUL1. Structural and biochemical analyses reveal that GLMN adopts a HEAT-like repeat fold that tightly binds the E2-interacting surface of RBX1, inhibiting CRL-mediated chain formation by the E2 CDC34. The structure explains the basis for GLMN's selectivity toward RBX1 over RBX2, and how disease-associated mutations disrupt GLMN-RBX1 interactions. Our study reveals a mechanism for RING E3 ligase regulation, whereby an inhibitor blocks E2 access, and raises the possibility that other E3s are likewise controlled by cellular proteins that mask E2-binding surfaces to mediate inhibition.

  6. Towards engineering hormone-binding globulins as drug delivery agents

    E-Print Network [OSTI]

    Chan, Wee Lee; Zhou, Aiwu; Read, Randy J.

    2014-11-26T23:59:59.000Z

    in optical thickness of the sensor tip. Cortisol was immobilised on the biosensor tip surface by forming an adduct of hydrocortisone 21-hemisuccinate and a pentylamine-biotin linker through an amide bond, then allowing the biotin moiety on this cortisol... adduct to bind to the streptavidin-conjugated biosensor tip. The cortisol- Towards Engineering Hormone-Binding Globulins as Drug Delivery Agents PLOS ONE | DOI:10.1371/journal.pone.0113402 November 26, 2014 4 / 21 conjugated sensors were immersed...

  7. Protein Oligomerization Through Domain Swapping: Role of Inter-molecular Interactions and

    E-Print Network [OSTI]

    Yang, Sichun

    show that prevention of domain swapping inhibits amyloid fibrils by 80%,11 and strongly support the idea that domain swapping has an important role in fibril formation. Domain swapping is a term used found to form domain-swapped configurations, such as the human prion,12,13 the SH3 domain,14,15 p13suc1

  8. Cross-domain Paraphrasing For Improving Language Modelling Using Out-of-domain Data

    E-Print Network [OSTI]

    Liu, X.; Gales, M. J. F.; Woodland, P. C.

    2014-01-01T23:59:59.000Z

    on the CU-HTK LVCSR system for conversational telephone speech used in the 2004 DARPA EARS evaluation. The acoustic models were trained on approx- imately 2000 hours of Fisher conversational speech released by the LDC. A 59k recognition word list was used... - plexity optimized interpolation weights: the LDC Fisher acous- tic transcriptions, Fisher, of 20 million words (0.75), and the University Washington conversational web data [3], UWWeb of 525 million words (0.18), and the out-of-domain broadcast news data...

  9. MANAGING TIGHT BINDING RECEPTORS FOR NEW SPEARATIONS TECHNOLOGIES

    SciTech Connect (OSTI)

    DARYLE H BUSCH RICHARD S GIVENS

    2004-12-10T23:59:59.000Z

    Much of the earth's pollution involves compounds of the metallic elements, including actinides, strontium, cesium, technetium, and RCRA metals. Metal ions bind to molecules called ligands, which are the molecular tools that can manipulate the metal ions under most conditions. This DOE-EMSP sponsored program strives (1) to provide the foundations for using the most powerful ligands in transformational separations technologies and (2) to produce seminal examples of their applications to separations appropriate to the DOE EM mission. These ultra tight-binding ligands can capture metal ions in the most competitive of circumstances (from mineralized sites, lesser ligands, and even extremely dilute solutions), but they react so slowly that they are useless in traditional separations methodologies. Two attacks on this problem are underway. The first accommodates to the challenging molecular lethargy by developing a seminal slow separations methodology termed the soil poultice. The second designs ligands that are only tight-binding while wrapped around the targeted metal ion, but can be put in place by switch-binding and removed by switch-release. We envision a kind of molecular switching process to accelerate the union between metal ion and tight-binding ligand. Molecular switching processes are suggested for overcoming the slow natural equilibration rate with which ultra tight-binding ligands combine with metal ions. Ligands that bind relatively weakly combine with metal ions rapidly, so the trick is to convert a ligand from a weak, rapidly binding species to a powerful, slow releasing ligand--during the binding of the ligand to the metal ion. Such switch-binding ligands must react with themselves, and the reaction must take place under the influence of the metal ion. For example, our generation 1 ligands showed that a well-designed linear ligand with ends that readily combine, forms a cyclic molecule when it wraps around a metal ion. Our generation 2 ligands are even more interesting. They convert from rings to structures that wrap around a metal ion to form a cage. These ligands are called cryptands. Switch release is accomplished by photolytic cleavage of a bond to convert a cyclic ligand into a linear ligand or to break similar bonds in a cryptate. Our studies have demonstrated switch binding and switch release with cryptates of calcium. These remarkable cyclic ligands and cage-like ligands are indeed tight-binding and may, in principle, be incorporated in various separations methodologies, including the soil poultice. The soil poultice mimics the way in which microbes secrete extremely powerful ligands into the soil in order to harvest iron. The cellular membrane of the microbe recognizes the iron/ligand complex and admits it into the cell. The soil poultice uses molecularly imprinted polymers (MIPs) to play the role of the cellular membrane. Imprinting involves creation of the polymer in the presence of the metal/ligand complex. In principle, a well design ligand/MIP combination can be highly selective toward almost any targeted metal ion. The principles for that design are the focus of these investigations. An imprinting molecule can interact with the polymer through any, some, or all of the so-called supramolecular modes; e.g., hydrogen bonding, electrostatic charge, minor ligand bonding, Pi-Pi stacking, and hydrophobic and van der Waals interactions. Historically these modes of binding have given MIPs only small re-binding capacities and very limited selectivities. This program has shown that each mode of interaction can be made more powerful than previously suspected and that combinations of different supramolecular interaction modes can produce remarkable synergisms. The results of this systematic study provide a firm foundation for tailoring molecular imprinted polymers for reclamation of specific metal ion, including those important to the DOE EM mission.

  10. Calculation of the strange quark mass using domain wall fermions

    E-Print Network [OSTI]

    Tom Blum; Amarjit Soni; Matthew Wingate

    2000-09-18T23:59:59.000Z

    We present a first calculation of the strange quark mass using domain wall fermions. This paper contains an overview of the domain wall discretization and a pedagogical presentation of the perturbative calculation necessary for computing the mass renormalization. We combine the latter with numerical simulations to estimate the strange quark mass. Our final result in the quenched approximation is 95(26) MeV in the ${\\bar{MS}}$ scheme at a scale of 2 GeV. We find that domain wall fermions have a small perturbative mass renormalization, similar to Wilson quarks, and exhibit good scaling behavior.

  11. NMR structure of the N-terminal domain of the replication initiator protein DnaA

    E-Print Network [OSTI]

    Lowery, Thomas J.

    2008-01-01T23:59:59.000Z

    NMR Structure of the N-terminal domain of the replication510-486-6059 Running title: N-terminal domain of DnaA Page 1and the specific role of the N-terminal domain remain poorly

  12. Clonal deletion of self-reactive T cells in irradiation bone marrow chimeras and neonatally tolerant mice. Evidence for intercellular transfer of Mlsa

    SciTech Connect (OSTI)

    Speiser, D.E.; Schneider, R.; Hengartner, H.; MacDonald, H.R.; Zinkernagel, R.M. (Univ. Hospital, Zuerich (Switzerland))

    1989-08-01T23:59:59.000Z

    Tolerance to Mlsa has been shown to be associated with clonal deletion of cells carrying TCR beta chain variable regions V beta 6 or V beta 8.1 in mice possessing I-E antigens. To evaluate the rules of tolerance induction to Mlsa we prepared irradiation bone marrow chimeras expressing Mlsa or Mlsb and I-E by different cell types. Deletion of V beta 6+, Mlsa-reactive T cells required the presence of Mlsa and I-E products either on bone marrow-derived cells or on irradiated recipient cells. Tolerance was induced when Mlsa and I-E were expressed by distinct cells of the chimera. Also neonatally tolerized mice exhibited depletion of V beta 6+ cells after injection of I-E- Mlsa spleen cells (DBA/1) into newborn I-E+ Mlsb mice (BALB/c x B10.G)F1. These results suggest that the product of the Mlsa locus is soluble and/or may be transferred from cell to cell and bound to I-E antigens. The chimera experiments also showed that tolerance to Mlsa is H-2 allele independent, i.e., is apparently unrestricted. Differentiation of chimeric (H-2d/Mlsa x H-2q/Mlsb)F1 stem cells in either an H-2d or an H-2q thymus revealed that tolerance assessed by absence of V beta 6+ T cells is not dependent on the thymically determined restriction specificity of T cells.

  13. Testin, a novel binding partner of the calcium-sensing receptor, enhances receptor-mediated Rho-kinase signalling

    SciTech Connect (OSTI)

    Magno, Aaron L. [Western Australian Institute for Medical Research and Centre for Medical Research, University of Western Australia, Nedlands, Western Australia 6009 (Australia) [Western Australian Institute for Medical Research and Centre for Medical Research, University of Western Australia, Nedlands, Western Australia 6009 (Australia); Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Hospital Avenue, Nedlands, Western Australia 6009 (Australia); Ingley, Evan [Western Australian Institute for Medical Research and Centre for Medical Research, University of Western Australia, Nedlands, Western Australia 6009 (Australia)] [Western Australian Institute for Medical Research and Centre for Medical Research, University of Western Australia, Nedlands, Western Australia 6009 (Australia); Brown, Suzanne J. [Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Hospital Avenue, Nedlands, Western Australia 6009 (Australia)] [Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Hospital Avenue, Nedlands, Western Australia 6009 (Australia); Conigrave, Arthur D. [School of Molecular Bioscience, University of Sydney, New South Wales 2000 (Australia)] [School of Molecular Bioscience, University of Sydney, New South Wales 2000 (Australia); Ratajczak, Thomas [Western Australian Institute for Medical Research and Centre for Medical Research, University of Western Australia, Nedlands, Western Australia 6009 (Australia) [Western Australian Institute for Medical Research and Centre for Medical Research, University of Western Australia, Nedlands, Western Australia 6009 (Australia); Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Hospital Avenue, Nedlands, Western Australia 6009 (Australia); Ward, Bryan K., E-mail: bryanw@cyllene.uwa.edu.au [Western Australian Institute for Medical Research and Centre for Medical Research, University of Western Australia, Nedlands, Western Australia 6009 (Australia); Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Hospital Avenue, Nedlands, Western Australia 6009 (Australia)

    2011-09-09T23:59:59.000Z

    Highlights: {yields} A yeast two-hybrid screen revealed testin bound to the calcium-sensing receptor. {yields} The second zinc finger of LIM domain 1 of testin is critical for interaction. {yields} Testin bound to a region of the receptor tail important for cell signalling. {yields} Testin and receptor interaction was confirmed in mammalian (HEK293) cells. {yields} Overexpression of testin enhanced receptor-mediated Rho signalling in HEK293 cells. -- Abstract: The calcium-sensing receptor (CaR) plays an integral role in calcium homeostasis and the regulation of other cellular functions including cell proliferation and cytoskeletal organisation. The multifunctional nature of the CaR is manifested through ligand-dependent stimulation of different signalling pathways that are also regulated by partner binding proteins. Following a yeast two-hybrid library screen using the intracellular tail of the CaR as bait, we identified several novel binding partners including the focal adhesion protein, testin. Testin has not previously been shown to interact with cell surface receptors. The sites of interaction between the CaR and testin were mapped to the membrane proximal region of the receptor tail and the second zinc-finger of LIM domain 1 of testin, the integrity of which was found to be critical for the CaR-testin interaction. The CaR-testin association was confirmed in HEK293 cells by coimmunoprecipitation and confocal microscopy studies. Ectopic expression of testin in HEK293 cells stably expressing the CaR enhanced CaR-stimulated Rho activity but had no effect on CaR-stimulated ERK signalling. These results suggest an interplay between the CaR and testin in the regulation of CaR-mediated Rho signalling with possible effects on the cytoskeleton.

  14. Multiple Glycogen-binding Sites in Eukaryotic Glycogen Synthase Are Required for High Catalytic Efficiency toward Glycogen

    SciTech Connect (OSTI)

    Baskaran, Sulochanadevi; Chikwana, Vimbai M.; Contreras, Christopher J.; Davis, Keri D.; Wilson, Wayne A.; DePaoli-Roach, Anna A.; Roach, Peter J.; Hurley, Thomas D. (Indiana-Med); (Des Moines U)

    2012-12-10T23:59:59.000Z

    Glycogen synthase is a rate-limiting enzyme in the biosynthesis of glycogen and has an essential role in glucose homeostasis. The three-dimensional structures of yeast glycogen synthase (Gsy2p) complexed with maltooctaose identified four conserved maltodextrin-binding sites distributed across the surface of the enzyme. Site-1 is positioned on the N-terminal domain, site-2 and site-3 are present on the C-terminal domain, and site-4 is located in an interdomain cleft adjacent to the active site. Mutation of these surface sites decreased glycogen binding and catalytic efficiency toward glycogen. Mutations within site-1 and site-2 reduced the V{sub max}/S{sub 0.5} for glycogen by 40- and 70-fold, respectively. Combined mutation of site-1 and site-2 decreased the V{sub max}/S{sub 0.5} for glycogen by >3000-fold. Consistent with the in vitro data, glycogen accumulation in glycogen synthase-deficient yeast cells ({Delta}gsy1-gsy2) transformed with the site-1, site-2, combined site-1/site-2, or site-4 mutant form of Gsy2p was decreased by up to 40-fold. In contrast to the glycogen results, the ability to utilize maltooctaose as an in vitro substrate was unaffected in the site-2 mutant, moderately affected in the site-1 mutant, and almost completely abolished in the site-4 mutant. These data show that the ability to utilize maltooctaose as a substrate can be independent of the ability to utilize glycogen. Our data support the hypothesis that site-1 and site-2 provide a 'toehold mechanism,' keeping glycogen synthase tightly associated with the glycogen particle, whereas site-4 is more closely associated with positioning of the nonreducing end during catalysis.

  15. Parallel Algorithms for Time and Frequency Domain Circuit Simulation

    E-Print Network [OSTI]

    Dong, Wei

    2010-10-12T23:59:59.000Z

    parallelization due to its explicit nature. For frequency-domain simulation, this dissertation presents a parallel harmonic balance approach, applicable to the steady-state and envelope-following analyses of both driven and autonomous circuits. The new approach...

  16. Log-domain circuit models of chemical reactions

    E-Print Network [OSTI]

    Mandal, Soumyajit

    We exploit the detailed similarities between electronics and chemistry to develop efficient, scalable bipolar or subthreshold log-domain circuits that are dynamically equivalent to networks of chemical reactions. Our ...

  17. Probing the mechanism of 3D-domain swapping

    E-Print Network [OSTI]

    Miller, Katherine Helen

    2011-01-01T23:59:59.000Z

    6. Schmid, F. X. (1992). Protein Folding. New York, Freeman.system for studying protein folding and domain swapping, wasa rate-limiting step in protein folding and unfolding, and

  18. 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...

  19. Status Report on Protected Domains for Cyber Infrastructure Management

    E-Print Network [OSTI]

    Irvine, Cynthia E.

    through the use of distributed, highly secure, protected domains. Instead of creating a costly physically, Network Security, Information Assurance 1 Introduction Currently, our national cyber infrastructure to the President for Cyber Space Security and Chairman, President's Critical Infrastructure Protection Board

  20. Distributed Kalman filtering compared to Fourier domain preconditioned conjugate gradient

    E-Print Network [OSTI]

    Greer, Julia R.

    Distributed Kalman filtering compared to Fourier domain preconditioned conjugate gradient for laser of the tomography problem. The second algorithm is the distributed Kalman filter (DKF) developed by Massioni et al

  1. Domain-specific Web Service Discovery with Service Class Descriptions

    SciTech Connect (OSTI)

    Rocco, D; Caverlee, J; Liu, L; Critchlow, T J

    2005-02-14T23:59:59.000Z

    This paper presents DynaBot, a domain-specific web service discovery system. The core idea of the DynaBot service discovery system is to use domain-specific service class descriptions powered by an intelligent Deep Web crawler. In contrast to current registry-based service discovery systems--like the several available UDDI registries--DynaBot promotes focused crawling of the Deep Web of services and discovers candidate services that are relevant to the domain of interest. It uses intelligent filtering algorithms to match services found by focused crawling with the domain-specific service class descriptions. We demonstrate the capability of DynaBot through the BLAST service discovery scenario and describe our initial experience with DynaBot.

  2. Decisions on Multivariate Time Series: Combining Domain Knowledge with

    E-Print Network [OSTI]

    Lin, Jessica

    ), Coppock Guide (CG), Consumer Confidence point drop (CCD), ISM Manufacturing Survey (ISM), and Negative specifically, we take the template of conditions identified by domain experts--such template consists

  3. A time and frequency domain analysis of contrarian trading strategies/

    E-Print Network [OSTI]

    Chaudhuri, Shomesh E

    2014-01-01T23:59:59.000Z

    This thesis applies time and frequency domain analyses to a high-frequency market making strategy to study the profitability of liquidity provision over multiple time horizons from 1964 to 2013. Using daily returns and ...

  4. Journal of Computational Acoustics, FREQUENCY DOMAIN WAVE PROPAGATION MODELLING

    E-Print Network [OSTI]

    Sheen, Dongwoo

    #11;ect de gas, brine or oil and gas-brine or gas-oil pore uids on seismic velocities. NumericalJournal of Computational Acoustics, f c IMACS FREQUENCY DOMAIN WAVE PROPAGATION MODELLING

  5. A multi-domain process design and improvement framework

    E-Print Network [OSTI]

    Nicol, Robert A. (Robert Arthur), 1969-

    2010-01-01T23:59:59.000Z

    Processes in manufacturing, services, and healthcare are complex socio-technical systems composed of intricately sequenced activities supported by elements drawn from multiple domains. While many of these processes offer ...

  6. The Isolated Sixth Gelsolin Repeat and Headpiece Domain of Villin...

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

    is an F-actin regulating, modular protein with a gelsolin-like core and a distinct C-terminal 'headpiece domain. Localized in the microvilli of the absorptive epithelium,...

  7. Axion cosmology with long-lived domain walls

    SciTech Connect (OSTI)

    Hiramatsu, Takashi [Yukawa Institute for Theoretical Physics, Kyoto University, Kitashirakawa Oiwake-cho, Sakyo-ku, Kyoto 606-8502 (Japan); Kawasaki, Masahiro; Saikawa, Ken'ichi [Institute for Cosmic Ray Research, The University of Tokyo, 5-1-5 Kashiwa-no-ha, Kashiwa City, Chiba 277-8582 (Japan); Sekiguchi, Toyokazu, E-mail: hiramatz@yukawa.kyoto-u.ac.jp, E-mail: kawasaki@icrr.u-tokyo.ac.jp, E-mail: saikawa@icrr.u-tokyo.ac.jp, E-mail: sekiguti@a.phys.nagoya-u.ac.jp [Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya City, Aichi 464-8602 (Japan)

    2013-01-01T23:59:59.000Z

    We investigate the cosmological constraints on axion models where the domain wall number is greater than one. In these models, multiple domain walls attached to strings are formed, and they survive for a long time. Their annihilation occurs due to the effects of explicit symmetry breaking term which might be raised by Planck-scale physics. We perform three-dimensional lattice simulations and compute the spectra of axions and gravitational waves produced by long-lived domain walls. Using the numerical results, we estimated relic density of axions and gravitational waves. We find that the existence of long-lived domain walls leads to the overproduction of cold dark matter axions, while the density of gravitational waves is too small to observe at the present time. Combining the results with other observational constraints, we find that the whole parameter region of models are excluded unless an unacceptable fine-tuning exists.

  8. Apron: A Library of Numerical Abstract Domains for Static Analysis

    E-Print Network [OSTI]

    Miné, Antoine

    Polka convex polyhedra linear equalities PPL + Wrapper convex polyhedra linear congruences Abstraction toolbox- mensions in vector spaces. Nevertheless, the domains implemented in the PPL can be interfaced to Apron

  9. antiferromagnetic domain fluctuations: Topics by E-print Network

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

    to the order parameter characterizing this process. R. Botet; M. Ploszajczak; A. Chbihi; B. Borderie; D. Durand; J. Frankland 2001-01-30 22 Time-Domain Detection of Weakly Coupled...

  10. Computations in Modules over Commutative Domains Alkiviadis G. Akritas

    E-Print Network [OSTI]

    Akritas, Alkiviadis G.

    of fractions K of this domain. The ring R may be canonically immersed in the field K. To solve a problem. More over this cost, in general, grows very quickly. For example, Gauss's method in the ring of integer

  11. Changes in misonidazole binding with hypoxic fraction in mouse tumors

    SciTech Connect (OSTI)

    Hirst, D.G.; Hazlehurst, J.L.; Brown, J.M.

    1985-07-01T23:59:59.000Z

    Binding of misonidazole (MISO) or a derivative to hypoxic cells in tumors has been proposed as a method for identifying tumors, and measuring their level of hypoxia. The author has recently shown that the hypoxic fraction of tumor cells can be altered over a wide range in vivo by acutely changing the hematocrit of the host animal by transfusion. The present study is aimed to investigate the changes in binding by /sup 14/C MISO that accompanied this procedure. Tumor bearing mice were injected with /sup 14/C MISO, irradiated with a single dose of X rays (20 Gy) and their tumor excised and bisected. One half of each tumor was used to determine cell survival in vitro, the other was used for /sup 14/C scintillation counting. As previously described, tumor cell survival was dramatically increased in acutely anemic mice and this was accompanied by an increase in /sup 14/C MISO binding to the tumors. The relationship between clonogenic cell survival and binding was found to be linear on a log-log plot for each of the tumor lines studied, but the slopes of the lines were different in different tumor lines and generally steeper than the value of 1.0 expected for a 1:1 correspondence between cells binding radioactivity and radiobiological resistance.

  12. Acid Gas Capture Using CO2-Binding Organic Liquids

    SciTech Connect (OSTI)

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

    2010-11-10T23:59:59.000Z

    Current chemical CO2 scrubbing technology is primarily aqueous alkanolamine based. These systems rapidly bind CO2 (forming water-soluble carbamate and bicarbonate salts) however, the process has serious disadvantages. The concentration of monoethanolamine rarely exceeds 30 wt % due to the corrosive nature of the solution, and this reduces the maximum CO2 volumetric (?108 g/L) and gravimetric capacity (?7 wt%) of the CO2 scrubber. The ?30 wt % loading of ethanolamine also means that a large excess of water must be pumped and heated during CO2 capture and release, and this greatly increases the energy requirements especially considering the high specific heat of water (4 j/g-1K-1). Our approach is to switch to organic systems that chemically bind CO2 as liquid alkylcarbonate salts. Our CO2-binding organic liquids have higher CO2 solubility, lower specific heats, potential for less corrosion and lower binding energies for CO2 than aqueous systems. CO2BOLs also reversibly bind and release mixed sulfur oxides. Furthermore the CO2BOL system can be direct solvent replacements for any solvent based CO2 capture systems because they are commercially available reagents and because they are fluids they would not require extensive process re-engineering.

  13. Dynamic Structural Rearrangements Between DNA Binding Modes of E. coli SSB Protein

    E-Print Network [OSTI]

    Lohman, Timothy M.

    an oligonucleotide/oligosaccharide bind- ing (OB) fold,5,79 hence the tetramer has four po- tential ssDNA binding sites. The SSB tetramer can bind long ssDNA in a variety of binding modes depending on solutionCl) and high protein to DNA ratios, an SSB tetramer binds to ssDNA with high inter-tetramer cooperativity using

  14. Seismic attenuation studies using frequency domain synthetic seismograms

    E-Print Network [OSTI]

    Butler, Theresa Meade

    1979-01-01T23:59:59.000Z

    SEISMIC ATTENUATION STUDIES USING FREQUENCY DOMAIN SYNTHETIC SEISMOGRAMS A Thesis by THERESA MEADE BUTLER Submitted to the Graduate College of Texas A&M University in partial fulfillment of the requirement for the degree of MASTER OF SCIENCE... August 1979 Major Subject: Geophysics SEISMIC ATTENUATION STUDIES USING FREQUENCY DOMAIN SYNTHETIC SEI SMOGRAMlS A Thesis by THERESA MEADE BUTLER Approved as to sty1e and content by: rman o Com ttee Head of epartmen (Member) Membe August 1979...

  15. Critical Ising interfaces in multiply-connected domains

    E-Print Network [OSTI]

    Konstantin Izyurov

    2015-03-13T23:59:59.000Z

    We prove a general result on convergence of interfaces in the critical planar Ising model to conformally invariant curves absolutely continuous with respect to SLE(3). Our setup includes multiple interfaces on arbitrary finitely connected domains, and we also treat the radial SLE case. In the case of simply and doubly connected domains, the limiting processes are described explicitly in terms of rational and elliptic functions, respectively.

  16. Amino-terminal domain stability mediates apolipoprotein E aggregation into neurotoxic fibrils

    E-Print Network [OSTI]

    Hatters, Danny M; Zhong, Ning; Rutenber, Earl; Weisgraber, Karl H

    2006-01-01T23:59:59.000Z

    et al. (2003) Carboxyl-terminal-truncated apolipoprotein E4the amino- and carboxyl-terminal domains. J. Biol. Chem. ,determined by the amino- terminal domain. Biochemistry, 39,

  17. Can adding oil control domain formation in binary amphiphile bilayers?

    E-Print Network [OSTI]

    M. J. Greenall; C. M. Marques

    2014-06-12T23:59:59.000Z

    Bilayers formed of two species of amphiphile of different chain lengths may segregate into thinner and thicker domains composed predominantly of the respective species. Using a coarse-grained mean-field model, we investigate how mixing oil with the amphiphiles affects the structure and thickness of the bilayer at and on either side of the boundary between two neighbouring domains. In particular, we find that oil molecules whose chain length is close to that of the shorter amphiphiles segregate to the thicker domain. This smooths the surface of the hydrophobic bilayer core on this side of the boundary, reducing its area and curvature and their associated free-energy penalties. The smoothing effect is weaker for oil molecules that are shorter or longer than this optimum value: short molecules spread evenly through the bilayer, while long molecules swell the thicker domain, increasing the surface area and curvature of the bilayer core in the interfacial region. Our results show that adding an appropriate oil could make the formation of domain boundaries more or less favourable, raising the possibility of controlling the domain size distribution.

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

    E-Print Network [OSTI]

    Ekstrom, A; Wendt, K A; Hagen, G; Papenbrock, T; Carlsson, B D; Forssen, C; Hjorth-Jensen, M; Navratil, P; Nazarewicz, W

    2015-01-01T23:59:59.000Z

    The accurate reproduction of nuclear radii and binding energies is a long-standing challenge in nuclear theory. To address this problem 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 3- states in 16O and 40Ca are described accurately, while spectra for selected p- and sd-shell nuclei are in reasonable agreement with experiment.

  19. Structure and Functional Characterization of the RNA-Binding Element of the NLRX1 Innate Immune Modulator

    SciTech Connect (OSTI)

    Hong, Minsun; Yoon, Sung-il; Wilson, Ian A. (Scripps)

    2012-06-20T23:59:59.000Z

    Mitochondrial NLRX1 is a member of the family of nucleotide-binding domain and leucine-rich-repeat-containing proteins (NLRs) that mediate host innate immunity as intracellular surveillance sensors against common molecular patterns of invading pathogens. NLRX1 functions in antiviral immunity, but the molecular mechanism of its ligand-induced activation is largely unknown. The crystal structure of the C-terminal fragment (residues 629975) of human NLRX1 (cNLRX1) at 2.65 {angstrom} resolution reveals that cNLRX1 consists of an N-terminal helical (LRRNT) domain, central leucine-rich repeat modules (LRRM), and a C-terminal three-helix bundle (LRRCT). cNLRX1 assembles into a compact hexameric architecture that is stabilized by intersubunit and interdomain interactions of LRRNT and LRRCT in the trimer and dimer components of the hexamer, respectively. Furthermore, we find that cNLRX1 interacts directly with RNA and supports a role for NLRX1 in recognition of intracellular viral RNA in antiviral immunity.

  20. Modulation of Pantothenate Kinase 3 Activity by Small Molecules that Interact with the Substrate/Allosteric Regulatory Domain

    SciTech Connect (OSTI)

    Leonardi, Roberta; Zhang, Yong-Mei; Yun, Mi-Kyung; Zhou, Ruobing; Zeng, Fu-Yue; Lin, Wenwei; Cui, Jimmy; Chen, Taosheng; Rock, Charles O.; White, Stephen W.; Jackowski, Suzanne (SJCH)

    2010-09-27T23:59:59.000Z

    Pantothenate kinase (PanK) catalyzes the rate-controlling step in coenzyme A (CoA) biosynthesis. PanK3 is stringently regulated by acetyl-CoA and uses an ordered kinetic mechanism with ATP as the leading substrate. Biochemical analysis of site-directed mutants indicates that pantothenate binds in a tunnel adjacent to the active site that is occupied by the pantothenate moiety of the acetyl-CoA regulator in the PanK3 acetyl-CoA binary complex. A high-throughput screen for PanK3 inhibitors and activators was applied to a bioactive compound library. Thiazolidinediones, sulfonylureas and steroids were inhibitors, and fatty acyl-amides and tamoxifen were activators. The PanK3 activators and inhibitors either stimulated or repressed CoA biosynthesis in HepG2/C3A cells. The flexible allosteric acetyl-CoA regulatory domain of PanK3 also binds the substrates, pantothenate and pantetheine, and small molecule inhibitors and activators to modulate PanK3 activity.

  1. Dissection and Manipulation of LRR Domains in Plant Disease Resistance Gene Products.

    SciTech Connect (OSTI)

    Bent, Andrew

    2012-11-28T23:59:59.000Z

    Leucine-rich repeat (LRR) protein domains offer a readily diversifiable platform - literally, an extended protein surface - for specific binding of very diverse ligands. The project addressed the following overlapping research questions: - How do leucine-rich repeat proteins recognize their cognate ligands? - What are the intra- and inter-molecular transitions that occur that cause transmembrane LRR proteins to switch between â??offâ? and â??onâ? states? - How do plants use LRR receptor proteins to activate disease resistance? - Can we synthetically evolve new LRR proteins that have acquired new ligand specificities? The following peer-reviewed primary research papers were published as part of the DOE-funded research: Sun*, W., Y. Cao*, K.L. Jansen, P. Bittel, T. Boller and A.F. Bent (*co-first authors), 2012. Probing the Arabidopsis flagellin receptor: FLS2-FLS2 association and the contributions of specific domains to signaling function. Plant Cell 24:1096-1113. DOI 10.1105/tpc.112.095919. Sun, W., L. Liu and A.F. Bent, 2011. Type III secretionâ??dependent host defense elicitation and Type III secretionâ??independent growth within leaves by Xanthomonas campestris pv.campestris. Mol. Plant Pathol. 12:731-745. DOI: 10.1111/J.1364-3703.2011.00707.X Helft, L., V. Reddy, X. Chen, T. Koller, L. Federici, J. Fernandez-Recio, R. Gupta and A. Bent, 2011. LRR Conservation Mapping to predict functional sites within protein leucine-rich repeat domains. PLoS ONE 6(7): e21614. doi:10.1371/journal.pone.0021614 Danna, C.H., Y.A. Millet, T. Koller, S.-W. Han, A.F. Bent, P.C. Ronald and F.M. Ausubel, 2011. The Arabidopsis flagellin receptor FLS2 mediates the perception of Xanthomonas Ax21 secreted peptides. Proc. Natl. Acad. Sci. (USA) 108:9286-9291. Two additional manuscripts are currently complete, one is submitted and is now being revised according to referee suggestions, and the other is not yet submitted. The provisional titles of those papers are: â??FLS2/BIK1/BAK1 Association and Dissociation are Not Sufficient to Activate Arabidopsis Immunity but FLS2 Phosphorylation Site Ser-938 is Required.â? and â??Directed Evolution of FLS2 towards Novel Flagellin Peptide Recognition.â? An additional tangible outcome of the work is the public availability of a bioinformatics website that we developed, www.plantpath.wisc.edu/RCM, where researchers can enter primary amino acid sequences for two or more related leucine-rich repeat proteins and use the program to identify sites on the predicted surface of the LRR that have been most conserved or most diversified across the proteins. These sites are typically the key functional sites on the protein, such as ligand binding sites. Despite a shift of DOE priorities away from support of research on plant immune system function, we are continuing our work on the engineering or in vitro evolution of LRR proteins toward novel ligand specificities.

  2. Molecular Cell High-Affinity Binding of Chp1 Chromodomain

    E-Print Network [OSTI]

    Halazonetis, Thanos

    Molecular Cell Article High-Affinity Binding of Chp1 Chromodomain to K9 Methylated Histone H3, Chp1, and siRNAs derived from centro- meric repeats. Recruitment of RITS to centromeres has been establishment. Our crystal structure of Chp1's chromodomain in complex with a trimethylated lysine 9 H3 peptide

  3. Workshop on gate valve pressure locking and thermal binding

    SciTech Connect (OSTI)

    Brown, E.J.

    1995-07-01T23:59:59.000Z

    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.

  4. Experimental study of exiton binding energy in semiconducting carbon nanotubes

    E-Print Network [OSTI]

    Maruyama, Shigeo

    and Technology (AIST), Tsukuba 305-8565, Japan 3 Global Edge Institute, Tokyo Institute of Technology, Tokyo, Japan 4 Departement of Mechanical Engineering, The University of Tokyo, Tokyo, Japan (Dated: July 21 dimensional nanotube leads to strong electron-hole localiza- tion, with binding energy as high as 0.5 e

  5. Parkin Binds to / Tubulin and Increases their Ubiquitination and Degradation

    E-Print Network [OSTI]

    Feng, Jian

    Parkin Binds to / Tubulin and Increases their Ubiquitination and Degradation Yong Ren, Jinghui Zhao depolymerize microtubules and increase tubulin degradation. Microtu- bules are polymers of tubulin. Misfolded tubulin monomers are highly toxic and quickly degraded through a hitherto unknown mechanism. Here

  6. Knowledge and Obedience: The Developmental Status of the Binding Theory

    E-Print Network [OSTI]

    Grimshaw, Jane; Rosen, Sara Thomas

    1990-04-05T23:59:59.000Z

    counterpart of sentences like Johnt tM Bill to shave him,. Thi binding relation is generally judged as ungrammatical, yet speakers preferred this interpretation to one in which the pronoun had no antecedent. K N O W I . h D O Ii A N D O B H D I H N C H 203...

  7. Thesis and Dissertation Archiving and Binding Request Form

    E-Print Network [OSTI]

    Bieber, Michael

    Thesis and Dissertation Archiving and Binding Request Form The Van Houten Library's digital copy is for archival purposes which will be accessible through NJIT's Electronic Theses & Dissertations website approved Master's Thesis or Doctoral Dissertation before it can be forwarded by the Graduate Studies Office

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

    SciTech Connect (OSTI)

    Calyam, Prasad

    2014-09-15T23:59:59.000Z

    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.

  9. The binding affinity of a soluble TCR-Fc fusion protein is significantly improved by crosslinkage with an anti-C{beta} antibody

    SciTech Connect (OSTI)

    Ozawa, Tatsuhiko; Horii, Masae; Kobayashi, Eiji [Department of Immunology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194 (Japan)] [Department of Immunology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194 (Japan); Jin, Aishun [Department of Immunology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194 (Japan) [Department of Immunology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194 (Japan); Department of Immunology, College of Basic Medical Sciences, Harbin Medical University, 157 Baojian Road, Nangang District, Harbin 150081 (China); Kishi, Hiroyuki, E-mail: immkishi@med.u-toyama.ac.jp [Department of Immunology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194 (Japan)] [Department of Immunology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194 (Japan); Muraguchi, Atsushi [Department of Immunology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194 (Japan)] [Department of Immunology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194 (Japan)

    2012-06-01T23:59:59.000Z

    Highlights: Black-Right-Pointing-Pointer A novel soluble TCR composed of TCR V and C regions with Ig Fc region is generated. Black-Right-Pointing-Pointer TCR-Fc protein immobilized by an anti-C{beta} antibody bound to a p/MHC tetramer. Black-Right-Pointing-Pointer Binding affinity of TCR-Fc was markedly increased by binding with anti-C{beta} antibody. -- Abstract: The identification and cloning of tumor antigen-specific T cell receptors (TCRs) and the production of the soluble form of the TCR (sTCR) contributed to the development of diagnostic and therapeutic tools for cancer. Recently, several groups have reported the development of technologies for the production of sTCRs. The native sTCR has a very low binding affinity for the antigenic peptide/MHC (p/MHC) complex. In this study, we established a technology to produce high affinity, functional sTCRs. We generated a novel sTCR-Fc fusion protein composed of the TCR V and C regions of the TCR linked to the immunoglobulin (Ig) Fc region. A Western blot analysis revealed that the molecular weight of the fusion protein was approximately 60 kDa under reducing conditions and approximately 100-200 kDa under non-reducing conditions. ELISAs using various antibodies showed that the structure of each domain of the TCR-Fc protein was intact. The TCR-Fc protein immobilized by an anti-C{beta} antibody effectively bound to a p/MHC tetramer. An SPR analysis showed that the TCR-Fc protein had a low binding affinity (KD; 1.1 Multiplication-Sign 10{sup -5} M) to the p/MHC monomer. Interestingly, when the TCR-Fc protein was pre-incubated with an anti-C{beta} antibody, its binding affinity for p/MHC increased by 5-fold (2.2 Multiplication-Sign 10{sup -6} M). We demonstrated a novel method for constructing a functional soluble TCR using the Ig Fc region and showed that the binding affinity of the functional sTCR-Fc was markedly increased by an anti-C{beta} antibody, which is probably due to the stabilization of the V{alpha}/V{beta} region of the TCR. These findings provide new insights into the binding of sTCRs to p/MHCs and will hopefully be instrumental in establishing functional sTCR as a diagnostic and therapeutic tool for cancer.

  10. 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. (Baylor)

    2012-05-29T23:59:59.000Z

    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.

  11. Fictitious domain methods for two-phase flow energy balance computations in nuclear

    E-Print Network [OSTI]

    Boyer, Edmond

    Fictitious domain methods for two-phase flow energy balance computations in nuclear components M, 2011 Abstract This paper is dedicated to the numerical simulation of nuclear components (Cores the physical domain under study in a Cartesian domain, called the fic- titious domain, and in performing

  12. High-Quality 2D Metal-Organic Coordination Network Providing Giant Cavities within Mesoscale Domains

    E-Print Network [OSTI]

    Brune, Harald

    -phase domains is particularly demanding. A recent step forward in this direction was an anthraquinone honeycomb

  13. Frequency-Domain Modeling Techniques for the Scalar Wave Equation : An Introduction

    E-Print Network [OSTI]

    Ajo-Franklin, Jonathan B.

    2005-01-01T23:59:59.000Z

    Frequency-domain finite-difference (FDFD) modeling offers several advantages over traditional timedomain

  14. The crystal structure of the mycobacterium tuberculosis Rv3019c-Rv3020c ESX complex reveals a domain-swapped heterotetramer

    SciTech Connect (OSTI)

    Arbing, Mark A.; Kaufmann, Markus; Phan, Tung; Chan, Sum; Cascio, Duilio; Eisenberg, David (UCLA)

    2010-11-15T23:59:59.000Z

    Mycobacterium tuberculosis encodes five gene clusters (ESX-1 to ESX-5) for Type VII protein secretion systems that are implicated in mycobacterial pathogenicity. Substrates for the secretion apparatus are encoded within the gene clusters and in additional loci that lack the components of the secretion apparatus. The best characterized substrates are the ESX complexes, 1:1 heterodimers of ESAT-6 and CFP-10, the prototypical member that has been shown to be essential for Mycobacterium tuberculosis pathogenesis. We have determined the structure of EsxRS, a homolog of EsxGH of the ESX-3 gene cluster, at 1.91 {angstrom} resolution. The EsxRS structure is composed of two four-helix bundles resulting from the 3D domain swapping of the C-terminal domain of EsxS, the CFP-10 homolog. The four-helix bundles at the extremities of the complex have a similar architecture to the structure of ESAT-6 {center_dot} CFP-10 (EsxAB) of ESX-1, but in EsxRS a hinge loop linking the {alpha}-helical domains of EsxS undergoes a loop-to-helix transition that creates the domain swapped EsxRS tetramer. Based on the atomic structure of EsxRS and existing biochemical data on ESX complexes, we propose that higher order ESX oligomers may increase avidity of ESX binding to host receptor molecules or, alternatively, the conformational change that creates the domain swapped structure may be the basis of ESX complex dissociation that would free ESAT-6 to exert a cytotoxic effect.

  15. Off-Shell NN Potential and Triton Binding Energy

    E-Print Network [OSTI]

    Y. Song; R. Machleidt

    1994-03-31T23:59:59.000Z

    The NONLOCAL Bonn-B potential predicts 8.0 MeV binding energy for the triton (in a charge-dependent 34-channel Faddeev calculation) which is about 0.4 MeV more than the predictions by LOCAL NN potentials. We pin down origin and size of the nonlocality in the Bonn potential, in analytic and numeric form. The nonlocality is due to the use of the correct off-shell Feynman amplitude of one-boson-exchange avoiding the commonly used on-shell approximations which yield the local potentials. We also illustrate how this off-shell behavior leads to more binding energy. We emphasize that the increased binding energy is not due to on-shell differences (differences in the fit of the NN data or phase shifts). In particular, the Bonn-B potential reproduces accurately the $\\epsilon_1$ mixing parameter up to 350 MeV as determined in the recent Nijmegen multi-energy NN phase-shift analysis. Adding the relativistic effect from the relativistic nucleon propagators in the Faddeev equations, brings the Bonn-B result up to 8.2 MeV triton binding. This leaves a difference of only 0.3 MeV to experiment, which may possibly be explained by refinements in the treatment of relativity and the inclusion of other nonlocalities (e.~g., quark-gluon exchange at short range). Thus, it is conceivable that a realistic NN potential which describes the NN data up to 300 MeV correctly may explain the triton binding energy without recourse to 3-N forces; relativity would play a major role for this result.

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

    SciTech Connect (OSTI)

    Hamlet, Jason R.; Keliiaa, Curtis M.

    2010-09-01T23:59:59.000Z

    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.

  17. Axion-Dilaton Domain Walls and Fake Supergravity

    E-Print Network [OSTI]

    Julian Sonner; Paul K. Townsend

    2007-05-07T23:59:59.000Z

    Dynamical systems methods are used to investigate domain-wall solutions of a two-parameter family of models in which gravity is coupled to an axion, and to a dilaton with an exponential potential of either sign. A complete global analysis is presented for (i) constant axion and (ii) flat walls, including a study of bifurcations and a new exact domain-wall solution with non-constant axion. We reconsider `fake supergravity' issues in light of these results. We show, by example, how domain walls determine multi-valued superpotentials that branch at stationary points that are not stationary points of the potential, and we apply this result to potentials with anti-de Sitter vacua. We also show by example that `adapted' truncation to a single-scalar model is sometimes inconsistent, and we propose a `generalized' fake supergravity formalism that applies in some such cases.

  18. Study of interdomain boundary in diamagnetic domain structure in beryllium

    E-Print Network [OSTI]

    Philip Lykov

    2002-11-21T23:59:59.000Z

    At low temperatures, in strong magnetic fields, the formation of a non-uniform magnetisation is possible in a single-crystal metal sample whose demagnetising factor along the field is close to unity. Namely, so-called Condon diamagnetic domain structure arises and disappears periodically with magnetic field. In this paper, the diamagnetic domain structure in beryllium single crystalis analysed. Directly, existence of diamagnetic domains in that sample was observed earlier by the muon spin precession (mSR) resonance peak splitting. A method is described that allows to calculate quantitative characteristics of the interdomain boundary using the muon histograms. The technique is based on the Marquardt minimisation procedure that has been modified in order to reduce the influence of noise on iterations convergence. Boundary volume fraction was calculated.

  19. Computer Forensics: you can hide but you canComputer Forensics: you can hide but you can''t deletet delete Dr. Nazli Hardy, 2009Reference: Computer Forensics: Principles and Practice

    E-Print Network [OSTI]

    Hardy, Christopher R.

    1 Computer Forensics: you can hide but you canComputer Forensics: you can hide but you can''t deletet delete Dr. Nazli Hardy, 2009Reference: Computer Forensics: Principles and Practice Volonino Anzaldua Godwin Computer Forensics April 10, 2009 Presentation for Dr. Maria Schiza's Forensics class

  20. Domain Wall Formation In The Post-Inflationary Universe

    E-Print Network [OSTI]

    Z. Lalak; S. Thomas

    1993-03-12T23:59:59.000Z

    We consider the evolution of the probability distribution $\\pp (\\chi ,\\chib, \\t)$, associated with an inhomogeneous light scalar field $\\chi$ in the Robertson-Walker Universe, where the inhomogeneities are produced by quantum fluctuations during an earlier inflationary epoch. For a specific choice of scalar potential which occurs in models of so called late-time phase transitions in which domain walls are produced, $\\pp$ is shown to evolve from a Gaussian to a non-Gaussian distribution. The structure of the latter justifies the recent use of 3-dimensional percolation theory to describe the initial distribution of domain walls in these models.

  1. Structural Insight into the Mechanism of Substrate Specificity and Catalytic Activity of an HD-Domain Phosphohydrolase: The 5;#8242;-Deoxyribonucleotidase YfbR from Escherichia coli

    SciTech Connect (OSTI)

    Zimmerman, Matthew D.; Proudfoot, Michael; Yakunin, Alexander; Minor, Wladek (Toronto); (UV)

    2011-08-16T23:59:59.000Z

    HD-domain phosphohydrolases have nucleotidase and phosphodiesterase activities and play important roles in the metabolism of nucleotides and in signaling. We present three 2.1-{angstrom}-resolution crystal structures (one in the free state and two complexed with natural substrates) of an HD-domain phosphohydrolase, the Escherichia coli 5'-nucleotidase YfbR. The free-state structure of YfbR contains a large cavity accommodating the metal-coordinating HD motif (H33, H68, D69, and D137) and other conserved residues (R18, E72, and D77). Alanine scanning mutagenesis confirms that these residues are important for activity. Two structures of the catalytically inactive mutant E72A complexed with Co{sup 2+} and either thymidine-5'-monophosphate or 2'-deoxyriboadenosine-5'-monophosphate disclose the novel binding mode of deoxyribonucleotides in the active site. Residue R18 stabilizes the phosphate on the Co{sup 2+}, and residue D77 forms a strong hydrogen bond critical for binding the ribose. The indole side chain of W19 is located close to the 2'-carbon atom of the deoxyribose moiety and is proposed to act as the selectivity switch for deoxyribonucleotide, which is supported by comparison to YfdR, another 5'-nucleotidase in E. coli. The nucleotide bases of both deoxyriboadenosine-5'-monophosphate and thymidine-5'-monophosphate make no specific hydrogen bonds with the protein, explaining the lack of nucleotide base selectivity. The YfbR E72A substrate complex structures also suggest a plausible single-step nucleophilic substitution mechanism. This is the first proposed molecular mechanism for an HD-domain phosphohydrolase based directly on substrate-bound crystal structures.

  2. DOI: 10.1002/cbic.200500285 Binding of Helix-Threading Peptides to E. coli

    E-Print Network [OSTI]

    Beal, Peter A.

    ] To further explore and develop the capabilities of the HTP design for binding RNA selectively, we identified duplex grooves. To further explore and develop the capabili- ties of the HTP design for binding RNA

  3. Glucose oxidation in heart-type fatty acid binding protein null mice

    E-Print Network [OSTI]

    Adhikari, Sean

    2006-10-30T23:59:59.000Z

    Heart-type fatty acid binding protein (H-FABP) is a major fatty acid binding factor in skeletal muscles. Genetic lack of H-FABP severely impairs the esterification and oxidation of exogenous fatty acids in soleus muscles ...

  4. 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...

  5. Characterization of Mg Binding to the DNA Repair ProteinApurinic...

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

    Mg Binding to the DNA Repair Protein ApurinicApyrimidic Endonuclease 1 via Solid-State Mg NMR Spectroscopy. Characterization of Mg Binding to the DNA Repair Protein Apurinic...

  6. acid-binding protein genes: Topics by E-print Network

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

    The adipocyte fatty acid-binding protein aP2 regulates systemic glucose (more) Shum, Bennett Oh Vic 2007-01-01 2 Fatty acid-binding protein in bovine skeletal muscle Texas A&M...

  7. aberrant fatty acid-binding: Topics by E-print Network

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

    The adipocyte fatty acid-binding protein aP2 regulates systemic glucose (more) Shum, Bennett Oh Vic 2007-01-01 2 Fatty acid-binding protein in bovine skeletal muscle Texas A&M...

  8. acid-binding protein ii: Topics by E-print Network

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

    The adipocyte fatty acid-binding protein aP2 regulates systemic glucose (more) Shum, Bennett Oh Vic 2007-01-01 2 Fatty acid-binding protein in bovine skeletal muscle Texas A&M...

  9. acid-binding immunoglobulin-like lectin-6: Topics by E-print...

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

    The adipocyte fatty acid-binding protein aP2 regulates systemic glucose (more) Shum, Bennett Oh Vic 2007-01-01 2 Fatty acid-binding protein in bovine skeletal muscle Texas A&M...

  10. Nucleon binding corrections to lepton-nucleus deep inelastic scattering: Use of a realistic spectral function

    SciTech Connect (OSTI)

    Dieperink, A.E.L.; Miller, G.A. (Department of Physics, FM-15, University of Washington, Seattle, Washington (USA))

    1991-08-01T23:59:59.000Z

    Nuclear spectral functions computed with realistic nuclear forces are used to compute mean separation energies and to estimate the binding corrections to lepton-nucleus deep inelastic scattering. The separation energies are large and significant binding effects are obtained.

  11. A familial {open_quotes}balanced{close_quotes} 3;9 translocation with cryptic 8q insertion leading to deletion and duplication of 9p23 loci in siblings

    SciTech Connect (OSTI)

    Wagstaff, J.; Hemann, M. [Harvard Medical School, Boston, MA (United States)

    1995-01-01T23:59:59.000Z

    A child with phenotypic features of the 9p{sup {minus}} syndrome, including metopic craniosynostosis, small ears, abdominal wall defect, and mental retardation, as well as hypopigmentation, was found to have a cytogenetically balanced 3;9 translocation, with breakpoints at 3p11 and 9p23, inherited from his phenotypically normal father. Molecular analysis showed heterozygous deletion of the TYRP (tyrosinase-related protein) locus, as well as loci D9S157, D9S274, D9S268, and D9S267, in the child but in neither parent. FISH analysis of the proband`s father indicated that loci deleted in his son, including TYRP, were present on neither the der(3) nor the der(9) translocation products but had been inserted into the long arm of chromosome 8. Therefore, the apparent deletion of these loci in the proband was the result of meiotic segregation of the father`s 3;9 translocation chromosomes together with his normal chromosome 8 (not bearing the insertion from 9p23). Neither the deletion of these 9p23 loci from the translocation chromosomes nor their insertion into 8q was detectable by standard chromosome banding techniques. The proband`s sister exhibited speech delay, mild facial dysmorphism, and renal malformation, and her karyotype was 46,XX. Molecular analysis showed that she had inherited normal chromosomes 3 and 9, as well as the chromosome 8 with the insertion of 9p23 material, from her father. This analysis illustrates a new mechanism to explain cases in which an apparently balanced translocation has been transmitted from a normal parent to a child with a phenotypic abnormality: submicroscopic deletion of material from the translocation breakpoint and insertion into a third chromosome in the balanced parent, with meiotic segregation leading to loss of the inserted material in the child. 36 refs., 9 figs., 1 tab.

  12. The Crystal Structure of Escherichia coli Group 4 Capsule Protein GfcC Reveals a Domain Organization Resembling That of Wza

    SciTech Connect (OSTI)

    Sathiyamoorthy, Karthik; Mills, Erez; Franzmann, Titus M.; Rosenshine, Ilan; Saper, Mark A. (Michigan); (Hebrew)

    2012-03-15T23:59:59.000Z

    We report the 1.9 {angstrom} resolution crystal structure of enteropathogenic Escherichia coli GfcC, a periplasmic protein encoded by the gfc operon, which is essential for assembly of group 4 polysaccharide capsule (O-antigen capsule). Presumed gene orthologs of gfcC are present in capsule-encoding regions of at least 29 genera of Gram-negative bacteria. GfcC, a member of the DUF1017 family, is comprised of tandem {beta}-grasp (ubiquitin-like) domains (D2 and D3) and a carboxyl-terminal amphipathic helix, a domain arrangement reminiscent of that of Wza that forms an exit pore for group 1 capsule export. Unlike the membrane-spanning C-terminal helix from Wza, the GfcC C-terminal helix packs against D3. Previously unobserved in a {beta}-grasp domain structure is a 48-residue helical hairpin insert in D2 that binds to D3, constraining its position and sequestering the carboxyl-terminal amphipathic helix. A centrally located and invariant Arg115 not only is essential for proper localization but also forms one of two mostly conserved pockets. Finally, we draw analogies between a GfcC protein fused to an outer membrane {beta}-barrel pore in some species and fusion proteins necessary for secreting biofilm-forming exopolysaccharides.

  13. Ultrastrong Optical Binding of Metallic Nanoparticles Vassili Demergis and Ernst-Ludwig Florin*

    E-Print Network [OSTI]

    Texas at Austin. University of

    Ultrastrong Optical Binding of Metallic Nanoparticles Vassili Demergis and Ernst-Ludwig Florin the optical binding force, which has been assumed to be weak compared to the optical gradient and scattering forces. We show that trapping by the optical binding force can be over 20 times stronger than

  14. DNA binding shifts the redox potential of the transcription factor SoxR

    E-Print Network [OSTI]

    Dietrich, Lars

    DNA binding shifts the redox potential of the transcription factor SoxR Alon A. Gorodetsky , Lars E-modified electrodes are used to probe the effects of binding to DNA on the redox potential of SoxR, a transcription in the absence of DNA. Using Redmond red as a covalently bound redox reporter affixed above the SoxR binding site

  15. Theory of Free Energy and Entropy in Noncovalent Binding Huan-Xiang Zhou*,

    E-Print Network [OSTI]

    Weston, Ken

    Theory of Free Energy and Entropy in Noncovalent Binding Huan-Xiang Zhou*, and Michael K. Gilson, Rockville, Maryland 20850 Received December 23, 2008 Contents 1. Introduction 4092 2. Free Energy, Partition.4. Solvation and a Temperature-Dependent Energy Function 4096 3. Binding Free Energy and Binding Constant 4096

  16. Efficient Evaluation of Binding Free Energy Using Continuum Electrostatics Danzhi Huang and Amedeo Caflisch*

    E-Print Network [OSTI]

    Caflisch, Amedeo

    Efficient Evaluation of Binding Free Energy Using Continuum Electrostatics Solvation Danzhi Huang of the absolute free energy of binding. A predictive accuracy of about 1.0 kcal/mol is obtained for 13 and 29 into proteins of known structure require fast and accurate methods for the evaluation of binding free energies.1

  17. Origin of the Variation of Exciton Binding Energy in Semiconductors Marc Dvorak,1

    E-Print Network [OSTI]

    Wu, Zhigang

    Origin of the Variation of Exciton Binding Energy in Semiconductors Marc Dvorak,1 Su-Huai Wei,2, and the exciton binding energy Eb in technologically important semiconductors varies from merely a few me between the electronic band structures and exciton binding energies in semiconductors, employing first

  18. Hierarchical Heuristic Forward Search in Stochastic Domains Nicolas Meuleau

    E-Print Network [OSTI]

    Brafman, Ronen

    and develop a variant of the AO* algorithm for performing for- ward heuristic search in hierarchical models. Substantial performance gains may be obtained in these algo- rithms by partitioning the set of search nodesHierarchical Heuristic Forward Search in Stochastic Domains Nicolas Meuleau NASA Ames Research

  19. ADAPTIVE FINITE ELEMENT FREQUENCY DOMAIN METHOD FOR EDDY CURRENT PROBLEMS

    E-Print Network [OSTI]

    Zheng, Weiying

    ADAPTIVE FINITE ELEMENT FREQUENCY DOMAIN METHOD FOR EDDY CURRENT PROBLEMS WEIYING ZHENG-harmonic eddy current problems in the case of three-dimensional isotropic and linear materials. We adopt. Time-harmonic Maxwell's equations, eddy current, adaptive finite element method, multiply connected

  20. Observational Constraints on Varying-alpha Domain Walls

    E-Print Network [OSTI]

    P. P. Avelino; L. Sousa

    2014-06-20T23:59:59.000Z

    We consider the possibility that current hints of a spatial variation of the fine structure constant at high redshift could be due to a biased domain wall network described by a scalar field non-minimally coupled to the electromagnetic field. We show that in order to be cause of the reported spatial variation of the fine structure constant without being in conflict with the observed anisotropies of the cosmic microwave background, the characteristic scale of the network would have to be of the order of the Hubble radius and the fractional contribution of the domain wall network to the energy density of the Universe would need to be in the range $10^{-10} temperature distribution of the cosmic microwave background detected by Planck and WMAP and provide a significant contribution to the excess B-mode polarisation power detected by BICEP2. Since the domain wall contribution to the cosmic energy budget only becomes important at late times, domain wall networks cannot play a significant role as a seed for large scale structure formation and primary cosmic microwave background anisotropies.

  1. Databases on the Web: national web domain survey Denis Shestakov

    E-Print Network [OSTI]

    Hammerton, James

    , Aalto University Konemiehentie 2, Espoo, 02150 Finland denis.shestakov@aalto.fi ABSTRACT The deep Web of the deep Web by sampling one national web domain. We report some of our results ob- tained when surveying the Russian Web. The survey find- ings, namely the size estimates of the deep Web, could be useful for further

  2. SUMTIME: KA For Weather Domain Page 1 of 20

    E-Print Network [OSTI]

    Sripada, Yaji

    News Inc, Aberdeen, UK) and gas turbine diagnosis (in collaboration with Intelligent Applications on a third (yet to be chosen) domain. In the case of gas turbine diagnosis, as is the case with the doctors of Aberdeen Aberdeen, UK {ssripada,ereiter,jhunter,jyu}@csd.abdn.ac.uk Abstract SUMTIME (http://www.csd.abdn.ac.in

  3. Abstract Domains of Affine Relations , T. Sharma1

    E-Print Network [OSTI]

    Reps, Thomas W.

    , and stud- ies how they relate to each other. We show that the abstract domains of M¨uller-Olm/Seidl (MOS for affine-relation analysis (ARA)--one defined by M¨uller-Olm and Seidl (MOS) [19, 21] and one defined

  4. TIME DOMAIN REFLECTOMETRY MEASUREMENT AND HIGHLY PLASTIC CLAYS

    E-Print Network [OSTI]

    Zornberg, Jorge G.

    1 TIME DOMAIN REFLECTOMETRY MEASUREMENT AND HIGHLY PLASTIC CLAYS By: J. A. Kuhn1 and J. G. Zornberg for use in highly plastic clay. The clay used for experimentation was taken locally from the Eagle Ford Ford Clay is determined. INTRODUCTION The progression of wetting and drying fronts in highly plastic

  5. Using Security and Domain ontologies for Security Requirements Analysis

    E-Print Network [OSTI]

    Paris-Sud XI, Universit de

    Using Security and Domain ontologies for Security Requirements Analysis Amina Souag, Camille.Mouratidis@uel.ac.uk Abstract-- Recent research has argued about the importance of considering security during Requirements that security being a multi-faceted problem, a single security ontology is not enough to guide SR Engineering

  6. Condorcet Domains; A Geometric Perspective Donald G. Saari

    E-Print Network [OSTI]

    Saari, Don

    Condorcet Domains; A Geometric Perspective Donald G. Saari Institute for Mathematical Behavioral decision process to cause fundamental theoretical concerns. As we now know (Saari [15]), for instance interpretations of Arrow's and Sen's theorems, see Saari [15]; also see Saari and Petron [17] and Li and Saari [8

  7. FACTS about threat Possible INTERVENTIONS Strong domain identification

    E-Print Network [OSTI]

    Chisholm, Rex L.

    FACTS about threat Possible INTERVENTIONS Strong domain identification heightens the effect are able to self affirm in difficult situations can lessen the effects of threat. Encourage students to use to students not under threat. Educate students on self talk! Teach them to pay close attention

  8. Conceptual modelling for domain specific document description and retrieval

    E-Print Network [OSTI]

    and are applied in the tasks of describing and retrieving documents, within cooperative document management settings, where the users themselves have to perform the document management tasks they need in orderConceptual modelling for domain specific document description and retrieval - An approach

  9. Analyzing Parallelism and Domain Similarities in the MAREC Patent Corpus

    E-Print Network [OSTI]

    Riezler, Stefan

    Analyzing Parallelism and Domain Similarities in the MAREC Patent Corpus Katharina W}@cl.uni-heidelberg.de Abstract. Statistical machine translation of patents requires large a- mounts of sentence-parallel data. Translations of patent text often exist for parts of the patent document, namely title, abstract and claims

  10. REPRESENTING GEO-SCIENTIFIC DOMAIN CONCEPTS Boyan Brodaric

    E-Print Network [OSTI]

    Bennett, Brandon

    1 REPRESENTING GEO-SCIENTIFIC DOMAIN CONCEPTS Boyan Brodaric Penn State Geography and Geological Survey of Canada brodaric@NRCan.gc.ca 1. Introduction The geo-sciences, including geology, ecology, soil accumulate and change, and (3) are characterized by degrees of uncertainty and granularity. This suggests

  11. Migrating a Domain-Specific Modeling Infrastructure to MDA Technology

    E-Print Network [OSTI]

    van Deursen, Arie

    Migrating a Domain-Specific Modeling Infrastructure to MDA Technology Duncan Doyle1,2, Hans Geers2 be migrated to models conform the MDA, in order to benefit from the range of MDA standards. We describe of the lessons learned. 1 Introduction The MDA promise of model-driven development is becoming a reality

  12. An Abstract Domain Extending Difference-Bound Matrices

    E-Print Network [OSTI]

    Paris-Sud XI, Université de

    " (or DBMs) is a domain proposed by David Dill, for expressing relations of the form "x - y c" or "c1 x c2". We define dDBMs ("disequalities DBMs") as conjunctions of DBMs with simple disequalities of the form "x = y" or "x = 0". We give algorithms on dDBMs, for deciding the emptiness, computing a normal

  13. Catalytic Domain of Phosphoinositide-specific Phospholipase C (PLC)

    E-Print Network [OSTI]

    Williams, Roger L.

    Catalytic Domain of Phosphoinositide-specific Phospholipase C (PLC) MUTATIONAL ANALYSIS OF RESIDUES WITHIN THE ACTIVE SITE AND HYDROPHOBIC RIDGE OF PLC 1* (Received for publication, November 20, 1997 Institute, University of Dundee, Dundee DD1 4HN, United Kingdom Structural studies of phospholipase C 1 (PLC

  14. Representing a Robotic Domain Using Temporal Description Logics

    E-Print Network [OSTI]

    Franconi, Enrico

    Representing a Robotic Domain Using Temporal Description Logics Alessandro Artale artale@irst.itc effects; effects may not directly follow the action but more complex temporal relations may hold describes a collection of properties of the world holding at a certain time. Actions are represented through

  15. SUBMIT TO IEEE TIP 1 Motion-Aware Gradient Domain

    E-Print Network [OSTI]

    O'Brien, James F.

    SUBMIT TO IEEE TIP 1 Motion-Aware Gradient Domain Video Composition Tao Chen, Jun-Yan Zhu, Ariel blending boundary based on a user provided blending trimap for the source video. Our approach extends mean performance. We also provide a user interface and source object positioning method that can efficiently deal

  16. A Logical Approach to Stable Domains Yi-Xiang Chen

    E-Print Network [OSTI]

    Jung, Achim

    The School of Mathematics, Physics and Informatics, Shanghai Normal University, Shanghai 200234, P.R. China- ingham, B15 2TT, England, A.Jung@cs.bham.ac.uk 1 #12;several unresolved issues. The central objects closed categories of algebraic domains and Scott- continuous functions [20], on the other hand, they form

  17. Time domain analog circuit simulation J.G. Fijnvandraat

    E-Print Network [OSTI]

    Eindhoven, Technische Universiteit

    of circuits in the electronics industry. Keywords: transient analysis, modified nodal analysis, differential be applied such as DC or steadystate anal ysis, Transient Analysis, ACanalysis (linear frequency domain analysis, after linearization around a DCsolution), Noise Analysis, Harmonic Balance (nonlinear frequency

  18. Time domain analog circuit simulation J.G. Fijnvandraat

    E-Print Network [OSTI]

    Eindhoven, Technische Universiteit

    of circuits in the electronics industry. Keywords: transient analysis, modified nodal analysis, differential be applied such as DC or steady-state anal- ysis, Transient Analysis, AC-analysis (linear frequency domain analysis, after linearization around a DC-solution), Noise Analysis, Harmonic Balance (non-linear frequency

  19. AN AGGREGATIONBASED DOMAIN DECOMPOSITION PRECONDITIONER FOR GROUNDWATER FLOW \\Lambda

    E-Print Network [OSTI]

    the standard finite element framework from [18,24]. The preconditioner also works well in the context of finiteAN AGGREGATION­BASED DOMAIN DECOMPOSITION PRECONDITIONER FOR GROUNDWATER FLOW \\Lambda E. W. JENKINS analysis of a two­level additive Schwarz method in which the coarse mesh basis is constructed

  20. AN AGGREGATION-BASED DOMAIN DECOMPOSITION PRECONDITIONER FOR GROUNDWATER FLOW

    E-Print Network [OSTI]

    . Our analysis uses the standard finite element framework from [18,24]. The preconditioner also works well in the context of finite differences, however, as some of the examples in £ 3 illustrateAN AGGREGATION-BASED DOMAIN DECOMPOSITION PRECONDITIONER FOR GROUNDWATER FLOW E. W. JENKINS ¡, C

  1. Hybrid Powertrain Design Using a Domain-Specific Modeling Environment

    E-Print Network [OSTI]

    Gray, Jeffrey G.

    Hybrid Powertrain Design Using a Domain- Specific Modeling Environment Wenzhong Gao1 , Sandeep environment is capable of rapidly assimilating new knowledge from experts and design database. Further, it can. As an example, the well-known worldwide recall in Spring 2002 of the BMW 745i was a direct result

  2. WHEELS: A CONVERSATIONAL SYSTEM IN THE AUTOMOBILE CLASSIFIEDS DOMAIN

    E-Print Network [OSTI]

    WHEELS: A CONVERSATIONAL SYSTEM IN THE AUTOMOBILE CLASSIFIEDS DOMAIN Helen Meng, Senis WHEELS is a conversational system which provides access to a database of eletronic automobile classified users to search through a database of 5,000 automobile classifieds. The current end-to-end system can re

  3. Improved value for the silicon free exciton binding energy

    SciTech Connect (OSTI)

    Green, Martin A., E-mail: m.green@unsw.edu.au [Australian Centre for Advanced Photovoltaics, School of Photovoltaic and Renewable Energy Engineering, University of New South Wales, Sydney, Australia 2052 (Australia)

    2013-11-15T23:59:59.000Z

    The free exciton binding energy is a key parameter in silicon material and device physics. In particular, it provides the necessary link between the energy threshold for valence to conduction band optical absorption and the bandgap determining electronic properties. The long accepted low temperature binding energy value of 14.7 0.4 meV is reassessed taking advantage of developments subsequent to its original determination, leading to the conclusion that this value is definitely an underestimate. Using three largely independent experimental data sets, an improved low temperature value of 15.01 0.06 meV is deduced, in good agreement with the most comprehensive theoretical calculations to date.

  4. A new phenomenological formula for ground state binding energies

    E-Print Network [OSTI]

    G. Gangopadhyay

    2010-07-09T23:59:59.000Z

    A phenomenological formula based on liquid drop model has been proposed for ground state binding energies of nuclei. The effect due to bunching of single particle levels has been incorporated through a term resembling the one-body Hamiltonian. The effect of n-p interaction has been included through a function of valence nucleons. A total of 50 parameters has been used in the present calculation. The r.m.s. deviation for the binding energy values for 2140 nuclei comes out to be 0.376 MeV, and that for 1091 alpha decay energies is 0.284 MeV. The correspondence with the conventional liquid drop model is discussed.

  5. Uranium Exerts Acute Toxicity by Binding to Pyrroloquinoline Quinone Cofactor

    SciTech Connect (OSTI)

    Michael R. VanEngelen; Robert I. Szilagyi; Robin Gerlach; Brady E. Lee; William A. Apel; Brent M. Peyton

    2011-02-01T23:59:59.000Z

    Uranium as an environmental contaminant has been shown to be toxic to eukaryotes and prokaryotes; however, no specific mechanisms of uranium toxicity have been proposed so far. Here a combination of in vivo, in vitro, and in silico studies are presented describing direct inhibition of pyrroloquinoline quinone (PQQ)-dependent growth and metabolism by uranyl cations. Electrospray-ionization mass spectroscopy, UV-vis optical spectroscopy, competitive Ca2+/uranyl binding studies, relevant crystal structures, and molecular modeling unequivocally indicate the preferred binding of uranyl simultaneously to the carboxyl oxygen, pyridine nitrogen, and quinone oxygen of the PQQ molecule. The observed toxicity patterns are consistent with the biotic ligand model of acute metal toxicity. In addition to the environmental implications, this work represents the first proposed molecular mechanism of uranium toxicity in bacteria, and has relevance for uranium toxicity in many living systems.

  6. Nuclear binding, correlations and the origin of EMC effect

    E-Print Network [OSTI]

    Omar Benhar; Ingo SIck

    2012-07-19T23:59:59.000Z

    Recent data for the slope of the EMC-ratio in the intermediate $x$-region for {\\em light} nuclei, with $3 \\leq A \\leq 12$, have the potential to shed new light on the origin of the EMC effect. Here we study the role of nuclear binding using the scaling variable ${\\tilde y}$, best suited to take into account this effect, and the understanding of the average nucleon removal energies, $\\bar{E}$, provided by state-of-the-art calculations based on nuclear many body theory. We find an excellent correlation between the new EMC data at $x \\sim 0.5$ and $\\bar{E}$ for nuclei with $A$ from 3 to $\\infty$, indicating that in this $x$ region binding is an important ingredient to explain the EMC effect. The role played by nucleon-nucleon correlations in this context is also discussed.

  7. Nuclear binding, correlations and the origin of EMC effect

    E-Print Network [OSTI]

    Benhar, Omar

    2012-01-01T23:59:59.000Z

    Recent data for the slope of the EMC-ratio in the intermediate $x$-region for {\\em light} nuclei, with $3 \\leq A \\leq 12$, have the potential to shed new light on the origin of the EMC effect. Here we study the role of nuclear binding using the scaling variable ${\\tilde y}$, best suited to take into account this effect, and the understanding of the average nucleon removal energies, $\\bar{E}$, provided by state-of-the-art calculations based on nuclear many body theory. We find an excellent correlation between the new EMC data at $x \\sim 0.5$ and $\\bar{E}$ for nuclei with $A$ from 3 to $\\infty$, indicating that in this $x$ region binding is an important ingredient to explain the EMC effect. The role played by nucleon-nucleon correlations in this context is also discussed.

  8. Screening a phage display library for a novel FGF8b-binding peptide with anti-tumor effect on prostate cancer

    SciTech Connect (OSTI)

    Wang, Wenhui; Chen, Xilei; Li, Tao; Li, Yanmei; Wang, Ruixue; He, Dan; Luo, Wu [Institute of Tissue Transplantation and Immunology, Jinan University, Guangzhou 510632 (China); Li, Xiaokun [Institute of Tissue Transplantation and Immunology, Jinan University, Guangzhou 510632 (China); School of Pharmaceutical Science, Wenzhou Medical College, Wenzhou 325035 (China); Wu, Xiaoping, E-mail: twxp@jnu.edu.cn [Institute of Tissue Transplantation and Immunology, Jinan University, Guangzhou 510632 (China); School of Pharmaceutical Science, Wenzhou Medical College, Wenzhou 325035 (China)

    2013-05-01T23:59:59.000Z

    Fibroblast growth factor 8b (FGF8b) is the major isoform of FGF8 expressed in prostate cancer and it correlates with the stage and grade of the disease. FGF8b has been considered as a potential target for prostate cancer therapy. Here we isolated 12 specific FGF8b-binding phage clones by screening a phage display heptapeptide library with FGF8b. The peptide (HSQAAVP, named as P12) corresponding to one of these clones showed high homology to the immunoglobulin-like (Ig-like) domain II(D2) of high-affinity FGF8b receptor (FGFR3c), contained 3 identical amino acids (AVP) to the authentic FGFR3 D2 sequence aa 163169 (LLAVPAA) directly participating in ligand binding, carried the same charges as its corresponding motif (aa163169) in FGFR3c, suggesting that P12 may have a greater potential to interrupt FGF8b binding to its receptors than other identified heptapeptides do. Functional analysis indicated that synthetic P12 peptides mediate significant inhibition of FGF8b-induced cell proliferation, arrest cell cycle at the G0/G1 phase via suppression of Cyclin D1 and PCNA, and blockade of the activations of Erk1/2 and Akt cascades in both prostate cancer cells and vascular endothelial cells. The results demonstrated that the P12 peptide acting as an FGF8b antagonist may have therapeutic potential in prostate cancer. - Highlights: ? A novel FGF8b-binding peptide P12 was isolated from a phage display library. ? The mechanisms for P12 peptide inhibiting cell proliferation were proposed. ? P12 caused cell cycle arrest at G0/G1 phase via suppression of Cyclin D1 and PCNA. ? P12 suppressed FGF8b-induced activations of Akt and MAP kinases. ? P12 acting as an FGF8b antagonist may have therapeutic potential in prostate cancer.

  9. ATM Networking in Linux Bindings occur at four distinct times

    E-Print Network [OSTI]

    Westall, James M.

    the following call: sock_register(pvc_proto_ops.family, &pvc_proto_ops); Family is PF_ATMPVC (as in PF_INET) pvc_len); : For ATM PVCs the structure is filled in as follows: static struct proto_ops pvc_proto_ops = { PF_ATMPVC, atm_create, pvc_dup, atm_release, pvc_bind, pvc_connect, : · The entry point addresses

  10. ATM Networking in Linux Bindings occur at four distinct times

    E-Print Network [OSTI]

    Westall, James M.

    using the following call: sock_register(pvc_proto_ops.family, &pvc_proto_ops); Family is PF_ATMPVC (as in PF_INET) pvc_proto_ops is a table of entry point addresses: struct proto_ops { int family; int_ops pvc_proto_ops = { PF_ATMPVC, atm_create, pvc_dup, atm_release, pvc_bind, pvc_connect, : . The entry

  11. Novel binding mechanism for ultra-long range molecules

    E-Print Network [OSTI]

    V. Bendkowsky; B. Butscher; J. Nipper; J. P. Shaffer; R. Loew; T. Pfau

    2008-09-17T23:59:59.000Z

    Molecular bonds can be divided into four primary types: ionic, covalent, van der Waals and hydrogen bonds. At ultralow temperatures a novel binding type emerges paving the way for novel molecules and ultracold chemistry [1,2]. The underlying mechanism for this new type of chemical bond is low-energy electron scattering of Rydberg electrons from polarisable ground state atoms [3]. This quantum scattering process can generate an attractive potential that is able to bind the ground state atom to the Rydberg atom at a well localized position within the Rydberg electron wave function. The resulting giant molecules can have an internuclear separation of several thousand Bohr radii, which places them among the largest known molecules to date. Their binding energies are much smaller than the Kepler frequencies of the Rydberg electrons i.e. the atomic Rydberg electron state is essentially unchanged by the bound ground state atom. Ultracold and dense samples of atoms enable the creation of these molecules via Rydberg excitation. In this paper we present spectroscopic evidence for the vibrational ground and first excited state of a Rubidium dimer Rb(5S)-Rb(nS). We apply a Born-Oppenheimer model to explain the measured binding energies for principal quantum numbers n between 34 and 40 and extract the s-wave scattering length for electron-Rb(5S) scattering in the relevant low energy regime Ekin < 100 meV. We also determine the lifetimes and the polarisabilities of these molecules. P-wave bound states [2], Trimer states [4] as well as bound states for large angular momentum of the Rydberg electron - socalled trilobite molecules [1] - are within reach in the near future and will further refine our conceptual understanding of the chemical bond.

  12. High molecular weight polysaccharide that binds and inhibits virus

    DOE Patents [OSTI]

    Konowalchuk, Thomas W

    2014-01-14T23:59:59.000Z

    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.

  13. Bounds to binding energies from the concavity of thermodynamical functions

    E-Print Network [OSTI]

    B. K. Jennings; B. R. Barrett; B. G. Giraud

    2007-08-22T23:59:59.000Z

    Sequences of experimental ground-state energies are mapped onto concave patterns cured from convexities due to pairing and/or shell effects. The same patterns, completed by a list of excitation energies, can be used to give numerical estimates of the grand potential $\\Omega(\\beta,\\mu)$ for a mixture of nuclei at low or moderate temperatures $T=\\beta^{-1}$ and at many chemical potentials $\\mu.$ The average nucleon number $(\\beta,\\mu)$ then becomes a continuous variable, allowing extrapolations towards nuclear masses closer to drip lines. We study the possible concavity of several thermodynamical functions, such as the free energy and the average energy, as functions of $.$ Concavity, when present in such functions, allows trivial interpolations and extrapolations providing upper and lower bounds, respectively, to binding energies. Such bounds define an error bar for the prediction of binding energies. An extrapolation scheme for such concave functions is tested. We conclude with numerical estimates of the binding energies of a few nuclei closer to drip lines.

  14. Substrate Binding Mode and its Implication on Drug Design for Botulinum Neurotoxin A

    SciTech Connect (OSTI)

    Kumaran, D.; Rawat, R; Ahmed, A; Swaminathan, S

    2008-01-01T23:59:59.000Z

    The seven antigenically distinct serotypes of Clostridium botulinum neurotoxins, the causative agents of botulism, block the neurotransmitter release by specifically cleaving one of the three SNARE proteins and induce flaccid paralysis. The Centers for Disease Control and Prevention (CDC) has declared them as Category A biowarfare agents. The most potent among them, botulinum neurotoxin type A (BoNT/A), cleaves its substrate synaptosome-associated protein of 25 kDa (SNAP-25). An efficient drug for botulism can be developed only with the knowledge of interactions between the substrate and enzyme at the active site. Here, we report the crystal structures of the catalytic domain of BoNT/A with its uncleavable SNAP-25 peptide 197QRATKM202 and its variant 197RRATKM202 to 1.5 A and 1.6 A, respectively. This is the first time the structure of an uncleavable substrate bound to an active botulinum neurotoxin is reported and it has helped in unequivocally defining S1 to S5? sites. These substrate peptides make interactions with the enzyme predominantly by the residues from 160, 200, 250 and 370 loops. Most notably, the amino nitrogen and carbonyl oxygen of P1 residue (Gln197) chelate the zinc ion and replace the nucleophilic water. The P1?-Arg198, occupies the S1? site formed by Arg363, Thr220, Asp370, Thr215, Ile161, Phe163 and Phe194. The S2? subsite is formed by Arg363, Asn368 and Asp370, while S3? subsite is formed by Tyr251, Leu256, Val258, Tyr366, Phe369 and Asn388. P4?-Lys201 makes hydrogen bond with Gln162. P5?-Met202 binds in the hydrophobic pocket formed by the residues from the 250 and 200 loop. Knowledge of interactions between the enzyme and substrate peptide from these complex structures should form the basis for design of potent inhibitors for this neurotoxin.

  15. Calculation of HVDC-converter harmonics in frequency domain with regard to asymmetries and comparison with time domain simulations

    SciTech Connect (OSTI)

    Rittiger, J. [Siemens AG, Erlangen (Germany)] [Siemens AG, Erlangen (Germany); Kulicke, B. [Technische Univ. Berlin (Germany)] [Technische Univ. Berlin (Germany)

    1995-10-01T23:59:59.000Z

    In order to study the effects of large HVDC converters to the feeding ac networks, it is of importance to explain and to calculate harmonic phenomena which are a result of converter operation. During commissioning of real HVDC converters it could be seen, that harmonics resulting from unsymmetries in the system voltages or from unsymmetries in converter operation led to significant difficulties concerning the system design. For this reason, not only the effects of characteristic but also the effects of noncharacteristic converter harmonics must be taken into account. The aim is to describe the steady state harmonic behavior of the converter. The harmonic spectra are not determined by time domain analysis but instead the solution is found by frequency domain calculations. This can result in reduced calculation time in comparison to conventional fourier analysis of the time functions. The converter is interpreted as an amplitude modulator with voltage and current converter functions which describe the coupling of the dc circuit and the ac network through the converter. To verify the theory, comparison of frequency domain with time domain calculations were carried out.

  16. Faster motion of double 360 domain walls system induced by spin-polarized current

    SciTech Connect (OSTI)

    Zhang, S. F.; Zhu, Q. Y.; Mu, C. P.; Zheng, Q.; Liu, X. Y.; Liu, Q. F.; Wang, J. B., E-mail: wangjb@lzu.edu.cn [Institute of Applied Magnetics, Key Laboratory for Magnetism and Magnetic Materials of Ministry of Education, Lanzhou University, Lanzhou 730000 (China)

    2014-05-07T23:59:59.000Z

    By micromagnetic simulation, we investigated a double 360 domain walls system in two parallel nanowires. Two domain walls are coupled to each other via magnetostatic interaction. When a spin-polarized current is applied to only one nanowire or both nanowires with the same direction, the two domain walls propagate along nanowires together. The critical velocity of such system is obviously higher than that of a single 360 domain wall. The interaction between the two domain walls can be modeled as two bodies that connected by a spring, and we analyzed the coupling characteritics of the double 360 domain walls at last.

  17. Deciphering the Effect of Nemaline-Myopathy Nebulin Mutations on Desmin Binding

    E-Print Network [OSTI]

    Jacobs, Krystyna M

    2012-07-11T23:59:59.000Z

    that desmin?s coil 2b binds as well to WT nebulin M160-164 to L5646A nebulin M160-164. ELISA assays were used to determine and compare the binding affinities (Kd) for the each of the nebulin fragments. Through ELISA assays we determined that the binding... nebulin M160-164 protein. The affinity constants (Kds) determined in experiment shown in Figure 6 are 10-fold different between the two samples. In particular, the lower Kd obtained for coil 2B binding to WT nebulin M160-164 suggests a stronger binding...

  18. High-Resolution NMR Structure of the Chemically-Synthesized Melanocortin Receptor Binding Domain AGRP(87-132) of the Agouti-Related Protein,

    E-Print Network [OSTI]

    Puglisi, Joseph

    and associated disorders such as diabetes are now at epidemic levels in the United States and other developed are directly implicated in energy balance. All MCRs are G-protein-coupled receptors (GPCRs) that up countries (1, 2). An understanding at the molecular level of the normal processes governing energy

  19. Binding deficits within the visual domain: an associative deficit characteristic of developmental dyslexia or merely a limitation in working memory capacity?

    E-Print Network [OSTI]

    Currie, Jennifer

    2010-06-30T23:59:59.000Z

    Dyslexics have reading difficulties which originate from the inability to accurately store and retrieve associations between a visual representation (grapheme) and the corresponding verbal representation (phoneme) in long ...

  20. Engagement of Nucleotide-Binding Oligomerization Domain-Containing Protein 1 (NOD1) by Receptor Interacting Protein 2 (RIP2) is Insufficient for Signal Transduction.

    E-Print Network [OSTI]

    Mayle, Sophie; Boyle, Joseph P.; Sekine, Eiki; Zurek, Birte; Kufer, Thomas A.; Monie, Tom P.

    2014-06-23T23:59:59.000Z

    that mutations in helix 2 of the CARD of NOD1 disrupted receptor function but did not interfere with RIP2 interaction. In particular, N43S, a rare polymorphism, resulted in receptor dysfunction despite retaining normal cellular localization, protein folding...

  1. Expression and accumulation of the two-domain odorant-binding protein AaegOBP45 in the ovaries of blood-fed Aedes aegypti

    E-Print Network [OSTI]

    Costa-da-Silva, Andr; Kojin, Bianca B; Marinotti, Osvaldo; James, Anthony A; Capurro, Margareth

    2013-01-01T23:59:59.000Z

    Nacional de Cincia e Tecnologia em Entomologia Molecular,Nacional de Cincia e Tecnologia em Entomologia Molecular,

  2. Homo-dimerization and ligand binding by the leucine-rich repeat domain at RHG1/RFS2 underlying resistance to two soybean pathogens

    E-Print Network [OSTI]

    2013-01-01T23:59:59.000Z

    change in free energy between the wild type protein (Pekingfree energy differences between the 3 mu- tants and the wild

  3. A familial {open_quotes}balanced{close_quotes} 3;9 translocation with cryptic 8q insertion leading to deletion and duplication of 9p23 loci in siblings

    SciTech Connect (OSTI)

    Wagstaff, J.; Hemann, M. [Children`s Hospital and Harvard Medical School, Boston, MA (United States)

    1994-09-01T23:59:59.000Z

    Families in which a balanced translocation has been transmitted from a normal parent to a child with a phenotypic abnormality have been a longstanding puzzle for human geneticists. A child with phenotypic features of the 9p- syndrome, including metopic craniosynostosis, small ears, abdominal wall defect, and mental retardation, was found to have a cytogenetically balanced 3;9 translocation, with breakpoints at 3p11 and 9p23, inherited from his normal father. He also exhibited marked hypopigmentation of hair and skin. Analysis with a cDNA probe from the TYRP1 (tyrosinase-related protein 1) gene in 9p23 showed heterozygous deletion in the child but in neither parent. This submicroscopic deletion also included loci D9S157, D9S274, D9S268, and D9S267. FISH analysis of the proband`s father indicated the 9p23 loci deleted in his son were present on neither the der(3) nor the der(9) translocation product, but had been inserted into the long arm of chromosome 8. Therefore, the apparent deletion of these loci in the proband was the result of meiotic segregation of the father`s 3;9 translocation chromosomes together with his normal chromosome 8. Neither the deletion from the translocation chromosomes nor the insertion into 8q was detectable by standard chromosome banding techniques. The proband`s sister exhibited speech delay, mild facial dysmorphism, and renal malformation, and her karyotype was 46,XX. Molecular analysis of this sister showed 3 copies of 9p23 sequences, indicating that she had inherited normal chromosomes 3 and 9 from her father as well as the chromosome 8 with the insertion from 9p23. This analysis illustrates a new mechanism to explain cases of phenotypic discordance in familial balanced translocations: submicroscopic deletion of material from the translocation breakpoint and insertion into a third chromosome in the balanced parent, with meiotic segregation leading to loss of the inserted material in the child.

  4. In-silico and in-vitro elucidation of BH3 binding specificity towards Bcl-2

    E-Print Network [OSTI]

    London, Nir

    Interactions between Bcl-2-like proteins and BH3 domains play a key role in the regulation of apoptosis. Despite the overall structural similarity of their interaction with helical BH3 domains, Bcl-2-like proteins exhibit ...

  5. NS1-binding protein abrogates the elevation of cell viability by the influenza A virus NS1 protein in association with CRKL

    SciTech Connect (OSTI)

    Miyazaki, Masaya [Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan)] [Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan); Nishihara, Hiroshi, E-mail: hnishihara@med.hokudai.ac.jp [Department of Translational Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan)] [Department of Translational Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan); Hasegawa, Hideki [Department of Pathology, National Institute of Infectious Diseases, Sinjuku-ku, Tokyo (Japan)] [Department of Pathology, National Institute of Infectious Diseases, Sinjuku-ku, Tokyo (Japan); Tashiro, Masato [Influenza Virus Research Center, National Institute of Infectious Diseases, Sinjuku-ku, Tokyo (Japan)] [Influenza Virus Research Center, National Institute of Infectious Diseases, Sinjuku-ku, Tokyo (Japan); Wang, Lei [Department of Translational Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan)] [Department of Translational Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan); Kimura, Taichi; Tanino, Mishie; Tsuda, Masumi [Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan)] [Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan); Tanaka, Shinya [Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan) [Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan); Department of Translational Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638 (Japan)

    2013-11-29T23:59:59.000Z

    Highlights: NS1 induced excessive phosphorylation of ERK and elevated cell viability. NS1-BP expression and CRKL knockdown abolished survival effect of NS1. NS1-BP and NS1 formed the complex through the interaction with CRKL-SH3(N). -- Abstract: The influenza A virus non-structural protein 1 (NS1) is a multifunctional virulence factor consisting of an RNA binding domain and several Src-homology (SH) 2 and SH3 binding motifs, which promotes virus replication in the host cell and helps to evade antiviral immunity. NS1 modulates general host cell physiology in association with various cellular molecules including NS1-binding protein (NS1-BP) and signaling adapter protein CRK-like (CRKL), while the physiological role of NS1-BP during influenza A virus infection especially in association with NS1 remains unclear. In this study, we analyzed the intracellular association of NS1-BP, NS1 and CRKL to elucidate the physiological roles of these molecules in the host cell. In HEK293T cells, enforced expression of NS1 of A/Beijing (H1N1) and A/Indonesia (H5N1) significantly induced excessive phosphorylation of ERK and elevated cell viability, while the over-expression of NS1-BP and the abrogation of CRKL using siRNA abolished such survival effect of NS1. The pull-down assay using GST-fusion CRKL revealed the formation of intracellular complexes of NS1-BP, NS1 and CRKL. In addition, we identified that the N-terminus SH3 domain of CRKL was essential for binding to NS1-BP using GST-fusion CRKL-truncate mutants. This is the first report to elucidate the novel function of NS1-BP collaborating with viral protein NS1 in modulation of host cell physiology. In addition, an alternative role of adaptor protein CRKL in association with NS1 and NS1-BP during influenza A virus infection is demonstrated.

  6. The metalloid arsenite induces nuclear export of Id3 possibly via binding to the N-terminal cysteine residues

    SciTech Connect (OSTI)

    Kurooka, Hisanori, E-mail: hkurooka@u-fukui.ac.jp [Division of Molecular Genetics, Department of Biochemistry and Bioinformative Sciences, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan) [Division of Molecular Genetics, Department of Biochemistry and Bioinformative Sciences, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan); Research and Education Program for Life Science, University of Fukui, Fukui (Japan); Sugai, Manabu [Department of Experimental Therapeutics, Translational Research Center, Kyoto University Hospital, Kyoto (Japan)] [Department of Experimental Therapeutics, Translational Research Center, Kyoto University Hospital, Kyoto (Japan); Mori, Kentaro [Division of Molecular Genetics, Department of Biochemistry and Bioinformative Sciences, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan)] [Division of Molecular Genetics, Department of Biochemistry and Bioinformative Sciences, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan); Yokota, Yoshifumi, E-mail: yokota@u-fukui.ac.jp [Division of Molecular Genetics, Department of Biochemistry and Bioinformative Sciences, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan) [Division of Molecular Genetics, Department of Biochemistry and Bioinformative Sciences, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan); Research and Education Program for Life Science, University of Fukui, Fukui (Japan)

    2013-04-19T23:59:59.000Z

    Highlights: Sodium arsenite induces cytoplasmic accumulation of Id3. Arsenite binds to closely spaced N-terminal cysteine residues of Id3. N-terminal cysteines are essential for arsenite-induced nuclear export of Id3. Nuclear export of Id3 counteracts its transcriptional repression activity. -- Abstract: Ids are versatile transcriptional repressors that regulate cell proliferation and differentiation, and appropriate subcellular localization of the Id proteins is important for their functions. We previously identified distinct functional nuclear export signals (NESs) in Id1 and Id2, but no active NES has been reported in Id3. In this study, we found that treatment with the stress-inducing metalloid arsenite led to the accumulation of GFP-tagged Id3 in the cytoplasm. Cytoplasmic accumulation was impaired by a mutation in the Id3 NES-like sequence resembling the Id1 NES, located at the end of the HLH domain. It was also blocked by co-treatment with the CRM1-specific nuclear export inhibitor leptomycin B (LMB), but not with the inhibitors for mitogen-activated protein kinases (MAPKs). Importantly, we showed that the closely spaced N-terminal cysteine residues of Id3 interacted with the arsenic derivative phenylarsine oxide (PAO) and were essential for the arsenite-induced cytoplasmic accumulation, suggesting that arsenite induces the CRM1-dependent nuclear export of Id3 via binding to the N-terminal cysteines. Finally, we demonstrated that Id3 significantly repressed arsenite-stimulated transcription of the immediate-early gene Egr-1 and that this repression activity was inversely correlated with the arsenite-induced nuclear export. Our results imply that Id3 may be involved in the biological action of arsenite.

  7. Functional clonal deletion versus suppressor cell-induced transplantation tolerance in chimeras prepared with a short course of total-lymphoid irradiation

    SciTech Connect (OSTI)

    Slavin, S.; Morecki, S.; Weigensberg, M.; Bar, S.; Weiss, L.

    1986-06-01T23:59:59.000Z

    Allogeneic bone marrow (BM) chimeras induced by infusion of BM cells into recipients conditioned with total lymphoid irradiation (TLI) were shown to develop humoral and cell-mediated tolerance to host and donor-type alloantigens by a number of in vitro and in vivo assays. Spleen cells of tolerant chimeras exhibited suppressive activity of mixed lymphocyte reaction (MLR). MLR suppression was not abrogated by depletion of Lyt-2 cells, and neither could Lyt-2-positive cells sorted from the spleens of tolerant chimeras suppress MLR or attenuate graft-versus-host reactivity in vivo. Likewise, specifically unresponsive spleen cells obtained from chimeras could not be induced to respond in MLR against tolerizing host-type cells following depletion of Lyt-2 or passage through a nylon-wool column. Tolerance of chimera spleen cells to host alloantigens, best documented by permanent survival of donor-type skin allografts, could be adoptively transferred into syngeneic recipients treated by heavy irradiation but not into untreated or mildly irradiated recipients. Adoptive transfer of tolerance seemed to be associated with experimental conditions favoring engraftment of tolerant cells rather than suppression of host reactivity. We speculate that although host and/or donor-derived suppressor cells may be operating in reducing the pool of specific alloreactive clones by blocking cell proliferation in response to allogeneic challenge, the final outcome in tolerant chimeras is actual or functional deletion of alloreactive clones.

  8. UNICOS CPC New Domains of Application: Vacuum and Cooling & Ventilation

    E-Print Network [OSTI]

    Willeman, D; Bradu, B; Ortola, J

    2011-01-01T23:59:59.000Z

    The UNICOS (UNified Industrial COntrol System) framework, and concretely the CPC (Continuous Process Control) package, has been extensively used in the domain of continuous processes (e.g. cryogenics, gas flows) and also in others specific to the LHC machine as the collimators environmental measurements interlock system. The application of the UNICOS-CPC to other kind of processes: vacuum and the cooling and ventilation cases are depicted here. One of the major challenges was to figure out whether the model and devices created so far were also adapted for other type of processes (e.g. Vacuum). To illustrate this challenge two domain use cases will be shown: ISOLDE vacuum control system and the RFQ4 and STP18 (cooling & ventilation) control systems. Both scenarios will be illustrated emphasizing the adaptability of the UNICOS CPC package to create those applications and highlighting the discovered needed features to include in a future version of the UNICOS CPC package. This paper will a...

  9. A TFETI Domain Decomposition Solver for Elastoplastic Problems

    E-Print Network [OSTI]

    ?ermk, M; Sysala, S; Valdman, J

    2012-01-01T23:59:59.000Z

    In the paper, we propose an algorithm for the efficient parallel implementation of elastoplastic problems with hardening based on the so-called TFETI (Total Finite Element Tearing and Interconnecting) domain decomposition method. We consider an associated elastoplastic model with the von Mises plastic criterion and the linear isotropic hardening law. Such a model is discretized by the implicit Euler method in time and the consequent one time step elastoplastic problem by the finite element method in space. The latter results in a system of nonlinear equations with a strongly semismooth and strongly monotone operator. The semismooth Newton method is applied to solve this nonlinear system. Corresponding linearized problems arising in the Newton iterations are solved in parallel by the above mentioned TFETI domain decomposition method. The proposed TFETI based algorithm was implemented in Matlab parallel environment and its performance was illustrated on a 3D elastoplastic benchmark. Numerical results for differ...

  10. Time Domain Partitioning of Electricity Production Cost Simulations

    SciTech Connect (OSTI)

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

    2014-01-01T23:59:59.000Z

    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.

  11. Stopbands in the existence domains of acoustic solitons

    SciTech Connect (OSTI)

    Nsengiyumva, F., E-mail: franco.nseng@gmail.com; Hellberg, M. A., E-mail: hellberg@ukzn.ac.za; Mace, R. L., E-mail: macer@ukzn.ac.za [School of Chemistry and Physics, University of KwaZulu-Natal, Durban 4000 (South Africa); Verheest, F., E-mail: frank.verheest@ugent.be [School of Chemistry and Physics, University of KwaZulu-Natal, Durban 4000 (South Africa); Sterrenkundig Observatorium, Universiteit Gent, Krijgslaan 281, B9000 Gent (Belgium)

    2014-10-15T23:59:59.000Z

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

  12. Stochastic domain decomposition for time dependent adaptive mesh generation

    E-Print Network [OSTI]

    Bihlo, Alexander; Walsh, Emily J

    2015-01-01T23:59:59.000Z

    The efficient generation of meshes is an important component in the numerical solution of problems in physics and engineering. Of interest are situations where global mesh quality and a tight coupling to the solution of the physical partial differential equation (PDE) is important. We consider parabolic PDE mesh generation and present a method for the construction of adaptive meshes in two spatial dimensions using stochastic domain decomposition that is suitable for an implementation in a multi- or many-core environment. Methods for mesh generation on periodic domains are also provided. The mesh generator is coupled to a time dependent physical PDE and the system is evolved using an alternating solution procedure. The method uses the stochastic representation of the exact solution of a parabolic linear mesh generator to find the location of an adaptive mesh along the (artificial) subdomain interfaces. The deterministic evaluation of the mesh over each subdomain can then be obtained completely independently us...

  13. Analysis of ultra-narrow ferromagnetic domain walls

    SciTech Connect (OSTI)

    Jenkins, Catherine; Paul, David

    2012-01-10T23:59:59.000Z

    New materials with high magnetic anisotropy will have domains separated by ultra-narrow ferromagnetic walls with widths on the order of a few unit cells, approaching the limit where the elastic continuum approximation often used in micromagnetic simulations is accurate. The limits of this approximation are explored, and the static and dynamic interactions with intrinsic crystalline defects and external driving #12;elds are modeled. The results developed here will be important when considering the stability of ultra-high-density storage media.

  14. An Energy Efficient Asynchronous Time-Domain Comparator

    E-Print Network [OSTI]

    Gao, Yang

    2013-04-26T23:59:59.000Z

    Approved by: Chair of Committee, Edgar Sanchez-Sinencio Committee Members, Sergiy Butenko Kamran Entesari Mi Lu Head of Department, Chanan Singh May 2013 Major Subject: Electrical Engineering Copyright 2013Yang Gao ii ABSTRACT...-domain comparators. iii DEDICATION To my parents and my beloved wife Qi iv ACKNOWLEDGEMENTS First, I would like to express my sincere thanks to my advisor, Dr. Edgar Sanchez-Sinencio for guidance, support and encouragement throughout my...

  15. On the use of the exponential window method in the space domain

    E-Print Network [OSTI]

    Liu, Li

    2009-05-15T23:59:59.000Z

    treatments. In this dissertation, an alternative is investigated based on the dynamic stiffness and the exponential window method in the space-wave number domain. Applying the exponential window in the space-wave number domain is equivalent to introducing...

  16. Current-driven Domain Wall Dynamics And Its Electric Signature In Ferromagnetic Nanowires

    E-Print Network [OSTI]

    Liu, Yang

    2012-10-19T23:59:59.000Z

    We study current-induced domain wall dynamics in a thin ferromagnetic nanowire. We derive the effective equations of domain wall motion, which depend on the wire geometry and material parameters. We describe the procedure to determine...

  17. Time-domain Simulation of Multibody Floating Systems based on State-space Modeling Technology

    E-Print Network [OSTI]

    Yu, Xiaochuan

    2012-10-19T23:59:59.000Z

    A numerical scheme to simulate time-domain motion responses of multibody floating systems has been successfully proposed. This scheme is integrated into a time-domain simulation tool, with fully coupled hydrodynamic ...

  18. A New Methodology for Frequency Domain Analysis of Wave Energy Converters with Periodically Varying Physical Parameters

    E-Print Network [OSTI]

    Victoria, University of

    A New Methodology for Frequency Domain Analysis of Wave Energy Converters with Periodically Varying Methodology for Frequency Domain Analysis of Wave Energy Converters with Periodically Varying Physical of Mechanical Engineering) ABSTRACT Within a wave energy converter's operational bandwidth, device operation

  19. One Work Analysis, Two Domains: A Display Information Requirements Case Study

    E-Print Network [OSTI]

    Cummings, M. L.

    2012-01-01T23:59:59.000Z

    d observations, among other techniques. Given the time and resources required, we examine how to generalize a work domain analysis technique, namely the hybrid Cognitive Task Analysis (hCTA) method across two domains in ...

  20. One Work Analysis, Two Domains: A Display Information Requirements Case Study

    E-Print Network [OSTI]

    Cummings, M. L.

    Work domain analyses can be time consuming, requiring extensive interviews, documentation review, and observations, among other techniques. Given the time and resources required, we examine how to generalize a work domain ...

  1. Modulation Domain Spectral Subtraction for Speech Enhancement Kuldip Paliwal, Belinda Schwerin, Kamil Wojcicki

    E-Print Network [OSTI]

    Modulation Domain Spectral Subtraction for Speech Enhancement Kuldip Paliwal, Belinda Schwerin- native to the acoustic domain for speech enhancement. More specifically, we wish to determine how achieves better back- ground noise reduction than the MMSE method. Index Terms: speech enhancement

  2. Structures of Domains I and IV from YbbR are representative of...

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

    of Domains I and IV from YbbR are representative of a widely distributed protein family. Structures of Domains I and IV from YbbR are representative of a widely distributed protein...

  3. Structural genomics reveals EVE as a new ASCH/PUA-related domain...

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

    reveals EVE as a new ASCHPUA-related domain. Structural genomics reveals EVE as a new ASCHPUA-related domain. Abstract: We report on a number of proteins recently solved by NESG...

  4. SUPPORTING DOMAIN SPECIFIC WEB-BASED SEARCH USING HEURISTIC KNOWLEDGE EXTRACTION

    E-Print Network [OSTI]

    Gunanathan, Sudharsan

    2010-01-16T23:59:59.000Z

    Modern search engines like Google support domain-independent search over the vast information contained in web documents. However domain-specific information access, such as finding less well-known people, locations, and ...

  5. Structural Insights into the Functional Role of the Hcn Sub-domain...

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

    is well documented and occurs via specific intermolecular interactions with the C-terminal sub-domain, Hcc, of BoNT-HCR. The N-terminal sub-domain of BoNT-HCR, Hcn, comprises...

  6. The Neurofascins orchestrate assembly and maintenance of axonal domains in the central nervous system

    E-Print Network [OSTI]

    Zonta, Barbara

    Close interaction between oligodendrocytes and axons is essential to initiate myelination and to form specialised domains along myelinated fibres. These domains are characterised by the assembly of protein complexes at ...

  7. Cross-domain comparison of quantitative technology improvement using patent derived characteristics

    E-Print Network [OSTI]

    Benson, Christopher Lee

    2014-01-01T23:59:59.000Z

    This thesis compares the performance improvement rates of 28 technological domains with characteristics derived from the patents of the domains, seeking to objectively test theories of how and why technologies change over ...

  8. Characterization of Cardio signals by time-frequency domain analysis

    E-Print Network [OSTI]

    Sayan Mukherjee; Sanjay Kumar Palit; Santo Banerjee; MRK Ariffin; Lamberto Rondoni; Dilip Kumar Bhattacharya

    2014-09-04T23:59:59.000Z

    Long term behavior of nonlinear deterministic continuous time signals can be studied in terms of their reconstructed attractors. Reconstructed attractors of a continuous signal are meant to be topologically equivalent representations of the dynamics of the unknown dynamical system which generates the signal. Sometimes, geometry of the attractor or its complexity may give important information on the system of interest. However, if the trajectories of the attractor behave as if they are not coming from continuous system or there exists many spike like structures on the path of the system trajectories, then there is no way to characterize the shape of the attractor. In this article, the traditional attractor reconstruction method is first used for two types of ECG signals: Normal healthy persons (NHP) and Congestive Heart failure patients (CHFP). As common in such a framework, the reconstructed attractors are not at all well formed and hence it is not possible to adequately characterize their geometrical features. Thus, we incorporate frequency domain information to the given time signals. This is done by transforming the signals to a time frequency domain by means of suitable Wavelet transforms (WT). The transformed signal concerns two non homogeneous variables and is still quite difficult to use to reconstruct some dynamics out of it. By applying a suitable mapping, this signal is further converted into integer domain and a new type of 3D plot, called integer lag plot, which characterizes and distinguishes the ECG signals of NHP and CHFP, is finally obtained.

  9. Proceedings of Symposia in Pure Mathematics Nodal domains on graphs -How to count them and why?

    E-Print Network [OSTI]

    Smilansky, Uzy

    by the pioneering work of Chladni on the nodal structures of vibrating plates. Counting nodal domains started

  10. Model-Based Mediation with Domain Maps Bertram Ludascher? Amarnath Gupta? Maryann E. Martonez

    E-Print Network [OSTI]

    Ludäscher, Bertram

    Model-Based Mediation with Domain Maps Bertram Lud¨ascher? Amarnath Gupta? Maryann E. Martonez ?San

  11. Second-order susceptibility from a tight-binding Hamiltonian

    E-Print Network [OSTI]

    Dumitrica, T.; Graves, JS; Allen, Roland E.

    1998-01-01T23:59:59.000Z

    measurements. In Sec. PRB 580163-1829/98/58~23!/15340~4!/$15.00 a tight-binding Hamiltonian , and R. E. Allen , College Station, Texas 77843 June 1998! g Hamiltonian to include interaction with a time- l expression for the second-order susceptibility... potential A; however, the term that is neglected ~involving PRB 58 BRIEF REPORT A2) does not give rise to electronic transitions in the long- wavelength approximation, since it can be eliminated through a unitary transformation.15 Only the last term...

  12. Hydroxyapatite-binding peptides for bone growth and inhibition

    DOE Patents [OSTI]

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

    2011-09-20T23:59:59.000Z

    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.

  13. Functionalized polymers for binding to solutes in aqueous solutions

    DOE Patents [OSTI]

    Smith, Barbara F.; Robison, Thomas W.

    2006-11-21T23:59:59.000Z

    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

  14. Characterization of Selective Binding of Alkali Cations with Carboxylate

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

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative1 First Use of Energy for All Purposes (Fuel and Nonfuel), 2002; Level: National5Sales for4,645 3,625govInstrumentstdmadapInactiveVisiting the TWPSuccessAlamosCharacterization of Selective Binding of Alkali Cations

  15. DNA-Binding Mechanism in Prokaryotic Partition Complex Formation

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

    AFDC Printable Version Share this resource Send a link to EERE: Alternative Fuels Data Center Home Page to someone by E-mail Share EERE: Alternative Fuels Data Center Home Page on Facebook Tweet about EERE: Alternative Fuels Data Center Home Page on Twitter Bookmark EERE: Alternative1 First Use of Energy for All Purposes (Fuel and Nonfuel), 2002; Level: National5Sales for4,645U.S. DOEThe Bonneville Power Administration wouldDECOMPOSITION OF CALCIUM SULFATE: A REVIEWThis rcportJ itDNA-Binding

  16. Pharmacological specificity of some psychotomimetic and antipsychotic agents for the sigma and PCP binding sites

    SciTech Connect (OSTI)

    Itzhak, Y.

    1988-01-01T23:59:59.000Z

    The pharmacological specificity of representative psychotomimetic agents such a phencyclidine (PCP) analogs, opiate benzomorphans and several antipsychotic agents was assessed for the sigma and PCP binding sites. In a series of binding experiments, in rat brain membranes, sigma and PCP binding sites were labeled with (/sup 3/H)-1-(1-(3-hydroxyphenyl) cyclohexyl) piperidine ((/sup 3/H)PCP-3-OH), (+)(/sup 3/H)-N-allylnormetazocine ((+)(/sup 3/H)SKF 10047) and (+) (/sup 3/H)-3-(3-hydroxy-phenyl)-N-(1-propyl) piperidine and ((+)(/sup 3/H)-3-PPP). PCP analogs inhibit potently high affinity (/sup 3/H)PCP-3-OH binding and (+)(/sup 3/H)SKF 10047 binding, moderately the low affinity binding component of (/sup 3/H)PCP-3-OH and very weakly (+) (/sup 3/H)-3-PPP binding. (+)SKF 10047 and cyclazocine are potent to moderate inhibitors of (+)(/sup 3/H)SKF 10047, high affinity (/sup 3/H)PCP-3-OH and (+)(/sup 3/H)-3-PCP-3-OH binding. The antipsychotic agents display high affinity for (+)(/sup 3/H)-3-PPP binding sites, moderate affinity for (+)(/sup 3/H)SKF 10047 sites and have no effect on either the high or low affinity (/sup 3/H)PCP-3-OH binding. 20 references, 3 figures, 2 tables.

  17. In-medium effects for nuclear matter in the Fermi energy domain D. Durand,1

    E-Print Network [OSTI]

    Boyer, Edmond

    In-medium effects for nuclear matter in the Fermi energy domain O. Lopez,1 D. Durand,1 G. Lehaut,1 of nuclear reactions in the Fermi energy domain. I. INTRODUCTION Transport properties in nuclear matter energy domain, transport features should exhibit the in- terplay between mean-field (nuclear degrees

  18. Phase-field simulation of strain-induced domain switching in magnetic thin films

    E-Print Network [OSTI]

    Chen, Long-Qing

    Phase-field simulation of strain-induced domain switching in magnetic thin films Jia-Mian Hu, G of the Bloch point in a magnetic film with strong uniaxial magnetic anisotropy Low Temp. Phys. 37, 690 (2011) Evolution of magnetic bubble domains in manganite films Appl. Phys. Lett. 99, 042503 (2011) 360 domain wall

  19. Time domain half-space dyadic Green's functions for eddy-current calculations

    E-Print Network [OSTI]

    Bowler, John R.

    Time domain half-space dyadic Green's functions for eddy-current calculations J. R. Bowlera) Centre American Institute of Physics. S0021-8979 99 08422-4 I. TIME DOMAIN INTERACTION The calculation of eddy-current-domain eddy-current scattering problems for cases in which a scat- terer is embedded in an otherwise

  20. A Study of Revenue Flows in Packet Networks under Multiple Administrative Domains

    E-Print Network [OSTI]

    A Study of Revenue Flows in Packet Networks under Multiple Administrative Domains Saadullah Tareenx that they usually only consider a single network and always consider a single administrative domain when for a detailed study of more realistic networks under multiple administrative domains. The interac- tions between