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Sample records for sh3 domain studied

  1. SH3 domain tyrosine phosphorylation--sites, role and evolution.

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    Zuzana Tatárová

    Full Text Available BACKGROUND: SH3 domains are eukaryotic protein domains that participate in a plethora of cellular processes including signal transduction, proliferation, and cellular movement. Several studies indicate that tyrosine phosphorylation could play a significant role in the regulation of SH3 domains. RESULTS: To explore the incidence of the tyrosine phosphorylation within SH3 domains we queried the PhosphoSite Plus database of phosphorylation sites. Over 100 tyrosine phosphorylations occurring on 20 different SH3 domain positions were identified. The tyrosine corresponding to c-Src Tyr-90 was by far the most frequently identified SH3 domain phosphorylation site. A comparison of sequences around this tyrosine led to delineation of a preferred sequence motif ALYD(Y/F. This motif is present in about 15% of human SH3 domains and is structurally well conserved. We further observed that tyrosine phosphorylation is more abundant than serine or threonine phosphorylation within SH3 domains and other adaptor domains, such as SH2 or WW domains. Tyrosine phosphorylation could represent an important regulatory mechanism of adaptor domains. CONCLUSIONS: While tyrosine phosphorylation typically promotes signaling protein interactions via SH2 or PTB domains, its role in SH3 domains is the opposite - it blocks or prevents interactions. The regulatory function of tyrosine phosphorylation is most likely achieved by the phosphate moiety and its charge interfering with binding of polyproline helices of SH3 domain interacting partners.

  2. Mobility of TOAC spin-labelled peptides binding to the Src SH3 domain studied by paramagnetic NMR

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    Lindfors, Hanna E. [Leiden University, Leiden Institute of Chemistry, Gorlaeus Laboratories (Netherlands); Koning, Peter E. de; Wouter Drijfhout, Jan [Leiden University Medical Centre, Department of Immunohematology and Blood Transfusion (Netherlands); Venezia, Brigida; Ubbink, Marcellus [Leiden University, Leiden Institute of Chemistry, Gorlaeus Laboratories (Netherlands)], E-mail: m.ubbink@chem.leidenuniv.nl

    2008-07-15

    Paramagnetic relaxation enhancement provides a tool for studying the dynamics as well as the structure of macromolecular complexes. The application of side-chain coupled spin-labels is limited by the mobility of the free radical. The cyclic, rigid amino acid spin-label TOAC (2,2,6,6-Tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid), which can be incorporated straightforwardly by peptide synthesis, provides an attractive alternative. In this study, TOAC was incorporated into a peptide derived from focal adhesion kinase (FAK), and the interaction of the peptide with the Src homology 3 (SH3) domain of Src kinase was studied, using paramagnetic NMR. Placing TOAC within the binding motif of the peptide has a considerable effect on the peptide-protein binding, lowering the affinity substantially. When the TOAC is positioned just outside the binding motif, the binding constant remains nearly unaffected. Although the SH3 domain binds weakly and transiently to proline-rich peptides from FAK, the interaction is not very dynamic and the relative position of the spin-label to the protein is well-defined. It is concluded that TOAC can be used to generate reliable paramagnetic NMR restraints.

  3. Mobility of TOAC spin-labelled peptides binding to the Src SH3 domain studied by paramagnetic NMR

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    Lindfors, Hanna E.; Koning, Peter E. de; Wouter Drijfhout, Jan; Venezia, Brigida; Ubbink, Marcellus

    2008-01-01

    Paramagnetic relaxation enhancement provides a tool for studying the dynamics as well as the structure of macromolecular complexes. The application of side-chain coupled spin-labels is limited by the mobility of the free radical. The cyclic, rigid amino acid spin-label TOAC (2,2,6,6-Tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid), which can be incorporated straightforwardly by peptide synthesis, provides an attractive alternative. In this study, TOAC was incorporated into a peptide derived from focal adhesion kinase (FAK), and the interaction of the peptide with the Src homology 3 (SH3) domain of Src kinase was studied, using paramagnetic NMR. Placing TOAC within the binding motif of the peptide has a considerable effect on the peptide-protein binding, lowering the affinity substantially. When the TOAC is positioned just outside the binding motif, the binding constant remains nearly unaffected. Although the SH3 domain binds weakly and transiently to proline-rich peptides from FAK, the interaction is not very dynamic and the relative position of the spin-label to the protein is well-defined. It is concluded that TOAC can be used to generate reliable paramagnetic NMR restraints

  4. SH3 Domains Differentially Stimulate Distinct Dynamin I Assembly Modes and G Domain Activity.

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    Sai Krishnan

    Full Text Available Dynamin I is a highly regulated GTPase enzyme enriched in nerve terminals which mediates vesicle fission during synaptic vesicle endocytosis. One regulatory mechanism involves its interactions with proteins containing Src homology 3 (SH3 domains. At least 30 SH3 domain-containing proteins bind dynamin at its proline-rich domain (PRD. Those that stimulate dynamin activity act by promoting its oligomerisation. We undertook a systematic parallel screening of 13 glutathione-S-transferase (GST-tagged endocytosis-related SH3 domains on dynamin binding, GTPase activity and oligomerisation. No correlation was found between dynamin binding and their potency to stimulate GTPase activity. There was limited correlation between the extent of their ability to stimulate dynamin activity and the level of oligomerisation, indicating an as yet uncharacterised allosteric coupling of the PRD and G domain. We examined the two variants, dynamin Iab and Ibb, which differ in the alternately splice middle domain α2 helix. They responded differently to the panel of SH3s, with the extent of stimulation between the splice variants varying greatly between the SH3s. This study reveals that SH3 binding can act as a heterotropic allosteric regulator of the G domain via the middle domain α2 helix, suggesting an involvement of this helix in communicating the PRD-mediated allostery. This indicates that SH3 binding both stabilises multiple conformations of the tetrameric building block of dynamin, and promotes assembly of dynamin-SH3 complexes with distinct rates of GTP hydrolysis.

  5. Detection and characterization of partially unfolded oligomers of the SH3 domain of α-Spectrin

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    Casares, S.; Sadqi, M.; López-Mayorga, O.; Conejero-Lara, F.; van Nuland, N.A.J.

    2004-01-01

    For the purpose of equilibrium and kinetic folding-unfolding studies, the SH3 domain of α-spectrin (spc-SH3) has long been considered a classic two-state folding protein. In this work we have indeed observed that the thermal unfolding curves of spc-SH3 measured at pH 3.0 by differential scanning

  6. Preferred SH3 domain partners of ADAM metalloproteases include shared and ADAM-specific SH3 interactions.

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    Iivari Kleino

    Full Text Available A disintegrin and metalloproteinases (ADAMs constitute a protein family essential for extracellular signaling and regulation of cell adhesion. Catalytic activity of ADAMs and their predicted potential for Src-homology 3 (SH3 domain binding show a strong correlation. Here we present a comprehensive characterization of SH3 binding capacity and preferences of the catalytically active ADAMs 8, 9, 10, 12, 15, 17, and 19. Our results revealed several novel interactions, and also confirmed many previously reported ones. Many of the identified SH3 interaction partners were shared by several ADAMs, whereas some were ADAM-specific. Most of the ADAM-interacting SH3 proteins were adapter proteins or kinases, typically associated with sorting and endocytosis. Novel SH3 interactions revealed in this study include TOCA1 and CIP4 as preferred partners of ADAM8, and RIMBP1 as a partner of ADAM19. Our results suggest that common as well as distinct mechanisms are involved in regulation and execution of ADAM signaling, and provide a useful framework for addressing the pathways that connect ADAMs to normal and aberrant cell behavior.

  7. Solution structure, dynamics and thermodynamics of the three SH3 domains of CD2AP

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    Roldan, Jose L. Ortega [Universidad de Granada, Departamento de Quimica Fisica e Instituto de Biotecnologia, Facultad de Ciencias (Spain); Blackledge, Martin [Institut de Biologie Structurale Jean-Pierre Ebel, CEA, CNRS, UJF UMR 5075, Protein Dynamics and Flexibility by NMR (France); Nuland, Nico A. J. van, E-mail: nvnuland@vub.ac.be [Vrije Universiteit Brussel, Structural Biology Brussels (Belgium); Azuaga, Ana I. [Universidad de Granada, Departamento de Quimica Fisica e Instituto de Biotecnologia, Facultad de Ciencias (Spain)

    2011-06-15

    CD2 associated protein (CD2AP) is an adaptor protein that plays an important role in cell to cell union needed for the kidney function. It contains three N-terminal SH3 domains that are able to interact among others with CD2, ALIX, c-Cbl and Ubiquitin. To understand the role of the individual SH3 domains of this adaptor protein we have performed a complete structural, thermodynamic and dynamic characterization of the separate domains using NMR and DSC. The energetic contributions to the stability and the backbone dynamics have been related to the structural features of each domain using the structure-based FoldX algorithm. We have found that the N-terminal SH3 domain of both adaptor proteins CD2AP and CIN85 are the most stable SH3 domains that have been studied until now. This high stability is driven by a more extensive network of intra-molecular interactions. We believe that this increased stabilization of N-terminal SH3 domains in adaptor proteins is crucial to maintain the necessary conformation to establish the proper interactions critical for the recruitment of their natural targets.

  8. Comparison of SH3 and SH2 domain dynamics when expressed alone or in an SH(3+2) construct: the role of protein dynamics in functional regulation.

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    Engen, J R; Smithgall, T E; Gmeiner, W H; Smith, D L

    1999-04-02

    Protein dynamics play an important role in protein function and regulation of enzymatic activity. To determine how additional interactions with surrounding structure affects local protein dynamics, we have used hydrogen exchange and mass spectrometry to investigate the SH2 and SH3 domains of the protein tyrosine kinase Hck. Exchange rates of isolated Hck SH3 and SH2 domains were compared with rates for the same domains when part of a larger SH(3+2) construct. Increased deuterium incorporation was observed for the SH3 domain in the joint construct, particularly near the SH2 interface and the short sequence that connects SH3 to SH2, implying greater flexibility of SH3 when it is part of SH(3+2). Slow cooperative unfolding of the SH3 domain occurred at the same rate in isolated SH3 as in the SH(3+2) construct, suggesting a functional significance for this unfolding. The SH2 domain displayed relatively smaller changes in flexibility when part of the SH(3+2) construct. These results suggest that the domains influence each other. Further, our results imply a link between functional regulation and structural dynamics of SH3 and SH2 domains. Copyright 1999 Academic Press.

  9. The Abl SH2-kinase linker naturally adopts a conformation competent for SH3 domain binding.

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    Chen, Shugui; Brier, Sébastien; Smithgall, Thomas E; Engen, John R

    2007-04-01

    The core of the Abelson tyrosine kinase (c-Abl) is structurally similar to Src-family kinases where SH3 and SH2 domains pack against the backside of the kinase domain in the down-regulated conformation. Both kinase families depend upon intramolecular association of SH3 with the linker joining the SH2 and kinase domains for suppression of kinase activity. Hydrogen deuterium exchange (HX) and mass spectrometry (MS) were used to probe intramolecular interaction of the c-Abl SH3 domain with the linker in recombinant constructs lacking the kinase domain. Under physiological conditions, the c-Abl SH3 domain undergoes partial unfolding, which is stabilized by ligand binding, providing a unique assay for SH3:linker interaction in solution. Using this approach, we observed dynamic association of the SH3 domain with the linker in the absence of the kinase domain. Truncation of the linker before W254 completely prevented cis-interaction with SH3, while constructs containing amino acids past this point showed SH3:linker interactions. The observation that the Abl linker sequence exhibits SH3-binding activity in the absence of the kinase domain is unique to Abl and was not observed with Src-family kinases. These results suggest that SH3:linker interactions may have a more prominent role in Abl regulation than in Src kinases, where the down-regulated conformation is further stabilized by a second intramolecular interaction between the C-terminal tail and the SH2 domain.

  10. New approaches to high-throughput structure characterization of SH3 complexes: the example of Myosin-3 and Myosin-5 SH3 domains from S. cerevisiae.

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    Musi, Valeria; Birdsall, Berry; Fernandez-Ballester, Gregorio; Guerrini, Remo; Salvatori, Severo; Serrano, Luis; Pastore, Annalisa

    2006-04-01

    SH3 domains are small protein modules that are involved in protein-protein interactions in several essential metabolic pathways. The availability of the complete genome and the limited number of clearly identifiable SH3 domains make the yeast Saccharomyces cerevisae an ideal proteomic-based model system to investigate the structural rules dictating the SH3-mediated protein interactions and to develop new tools to assist these studies. In the present work, we have determined the solution structure of the SH3 domain from Myo3 and modeled by homology that of the highly homologous Myo5, two myosins implicated in actin polymerization. We have then implemented an integrated approach that makes use of experimental and computational methods to characterize their binding properties. While accommodating their targets in the classical groove, the two domains have selectivity in both orientation and sequence specificity of the target peptides. From our study, we propose a consensus sequence that may provide a useful guideline to identify new natural partners and suggest a strategy of more general applicability that may be of use in other structural proteomic studies.

  11. Understanding the role of BAR and SH3 domain-containing proteins in fungi

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    Gkourtsa, A.

    2017-01-01

    This thesis addresses the role of SH3 and BAR domain-containing proteins in different fungal species. SH3 domains are small modules that mediate protein-protein interactions and BAR domains are dimerization domains with membrane binding and bending properties. It is known that the ScRvs167 protein

  12. Theoretical Insights Reveal Novel Motions in Csk's SH3 Domain That Control Kinase Activation.

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    Sulyman Barkho

    Full Text Available The Src family of tyrosine kinases (SFKs regulate numerous aspects of cell growth and differentiation and are under the principal control of the C-terminal Src Kinase (Csk. Although Csk and SFKs share conserved kinase, SH2 and SH3 domains, they differ considerably in three-dimensional structure, regulatory mechanism, and the intrinsic kinase activities. Although the SH2 and SH3 domains are known to up- or down-regulate tyrosine kinase function, little is known about the global motions in the full-length kinase that govern these catalytic variations. We use a combination of accelerated Molecular Dynamics (aMD simulations and experimental methods to provide a new view of functional motions in the Csk scaffold. These computational studies suggest that high frequency vibrations in the SH2 domain are coupled through the N-terminal lobe of the kinase domain to motions in the SH3 domain. The effects of these reflexive movements on the kinase domain can be viewed using both Deuterium Exchange Mass Spectrometry (DXMS and steady-state kinetic methods. Removal of several contacts, including a crystallographically unobserved N-terminal segment, between the SH3 and kinase domains short-circuit these coupled motions leading to reduced catalytic efficiency and stability of N-lobe motifs within the kinase domain. The data expands the model of Csk's activation whereby separate domains productively interact with two diametrically opposed surfaces of the kinase domain. Such reversible transitions may organize the active structure of the tyrosine kinase domain of Csk.

  13. Bayesian modeling of the yeast SH3 domain interactome predicts spatiotemporal dynamics of endocytosis proteins.

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    Raffi Tonikian

    2009-10-01

    Full Text Available SH3 domains are peptide recognition modules that mediate the assembly of diverse biological complexes. We scanned billions of phage-displayed peptides to map the binding specificities of the SH3 domain family in the budding yeast, Saccharomyces cerevisiae. Although most of the SH3 domains fall into the canonical classes I and II, each domain utilizes distinct features of its cognate ligands to achieve binding selectivity. Furthermore, we uncovered several SH3 domains with specificity profiles that clearly deviate from the two canonical classes. In conjunction with phage display, we used yeast two-hybrid and peptide array screening to independently identify SH3 domain binding partners. The results from the three complementary techniques were integrated using a Bayesian algorithm to generate a high-confidence yeast SH3 domain interaction map. The interaction map was enriched for proteins involved in endocytosis, revealing a set of SH3-mediated interactions that underlie formation of protein complexes essential to this biological pathway. We used the SH3 domain interaction network to predict the dynamic localization of several previously uncharacterized endocytic proteins, and our analysis suggests a novel role for the SH3 domains of Lsb3p and Lsb4p as hubs that recruit and assemble several endocytic complexes.

  14. Distinct ubiquitin binding modes exhibited by SH3 domains: molecular determinants and functional implications.

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    Jose L Ortega Roldan

    Full Text Available SH3 domains constitute a new type of ubiquitin-binding domains. We previously showed that the third SH3 domain (SH3-C of CD2AP binds ubiquitin in an alternative orientation. We have determined the structure of the complex between first CD2AP SH3 domain and ubiquitin and performed a structural and mutational analysis to decipher the determinants of the SH3-C binding mode to ubiquitin. We found that the Phe-to-Tyr mutation in CD2AP and in the homologous CIN85 SH3-C domain does not abrogate ubiquitin binding, in contrast to previous hypothesis and our findings for the first two CD2AP SH3 domains. The similar alternative binding mode of the SH3-C domains of these related adaptor proteins is characterised by a higher affinity to C-terminal extended ubiquitin molecules. We conclude that CD2AP/CIN85 SH3-C domain interaction with ubiquitin constitutes a new ubiquitin-binding mode involved in a different cellular function and thus changes the previously established mechanism of EGF-dependent CD2AP/CIN85 mono-ubiquitination.

  15. Molecular dissection of the interaction between the SH3 domain and the SH2-Kinase Linker region in PTK6.

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    Kim, Han Ie; Jung, Jinwon; Lee, Eun-Saem; Kim, Yong-Chul; Lee, Weontae; Lee, Seung-Taek

    2007-11-03

    PTK6 (also known as Brk) is an intracellular tyrosine kinase that contains SH3, SH2, and tyrosine kinase catalytic (Kinase) domains. The SH3 domain of PTK6 interacts with the N-terminal half of the linker (Linker) region between the SH2 and Kinase domains. Site-directed mutagenesis and surface plasmon resonance studies showed that a tryptophan residue (Trp44) in the SH3 domain and proline residues in the Linker region, in the order of Pro177, Pro175, and Pro179, contribute to the interaction. The three-dimensional modeled structure of the SH3-Linker complex was in agreement with the biochemical data. Disruption of the intramolecular interaction between the SH3 domain and the Linker region by mutation of Trp44, Pro175, Pro177, and Pro179 markedly increased the catalytic activity of PTK6 in HEK 293 cells. These results demonstrate that Trp44 in the SH3 domain and Pro177, Pro175, and Pro179 in the N-terminal half of the Linker region play important roles in the SH3-Linker interaction to maintain the protein in an inactive conformation along with the phosphorylated Tyr447-SH2 interaction.

  16. Structure determination of human Lck unique and SH3 domains by nuclear magnetic resonance spectroscopy

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    Willbold Dieter

    2003-05-01

    Full Text Available Abstract Background Protein tyrosine kinases are involved in signal transduction pathways that regulate cell growth, differentiation, activation and transformation. Human lymphocyte specific kinase (Lck is a 56 kDa protein involved in T-cell- and IL2-receptor signaling. Three-dimensional structures are known for SH3, SH2 and kinase domains of Lck as well as for other tyrosine kinases. No structure is known for the unique domain of any Src-type tyrosine kinase. Results Lck(1–120 comprising unique and SH3 domains was structurally investigated by nuclear magnetic resonance spectroscopy. We found the unique domain, in contrast to the SH3 part, to have basically no defined structural elements. The solution structure of the SH3 part could be determined with very high precision. It does not show significant differences to Lck SH3 in the absence of the unique domain. Minor differences were observed to the X-ray structure of Lck SH3. Conclusion The unique domain of Lck does not contain any defined structure elements in the absence of ligands and membranes. Presence of the unique domain is not relevant to the three-dimensional structure of the Lck SH3 domain.

  17. Functional analysis of SH3 domain containing ring finger 2 during the myogenic differentiation of quail myoblast cells

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    Si Won Kim

    2017-08-01

    Full Text Available Objective Owing to the public availability of complete genome sequences, including avian species, massive bioinformatics analyses may be conducted for computational gene prediction and the identification of gene regulatory networks through various informatics tools. However, to evaluate the biofunctional activity of a predicted target gene, in vivo and in vitro functional genomic analyses should be a prerequisite. Methods Due to a lack of quail genomic sequence information, we first identified the partial genomic structure and sequences of the quail SH3 domain containing ring finger 2 (SH3RF2 gene. Subsequently, SH3RF2 was knocked out using clustered regularly interspaced short palindromic repeat/Cas9 technology and single cell-derived SH3RF2 mutant sublines were established to study the biofunctional activity of SH3RF2 in quail myoblast (QM7 cells during muscle differentiation. Results Through a T7 endonuclease I assay and genotyping analysis, we established an SH3RF2 knockout (KO QM7#4 subline with 61 and 155 nucleotide deletion mutations in SH3RF2. After the induction of myotube differentiation, the expression profiles were analyzed and compared between regular QM7 and SH3RF2 KO QM7#4 cells by global RNA sequencing and bioinformatics analysis. Conclusion We did not detect any statistically significant role of SH3RF2 during myotube differentiation in QM7 myoblast cells. However, additional experiments are necessary to examine the biofunctional activity of SH3RF2 in cell proliferation and muscle growth.

  18. Abl N-terminal cap stabilization of SH3 domain dynamics.

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    Chen, Shugui; Dumitrescu, Teodora Pene; Smithgall, Thomas E; Engen, John R

    2008-05-27

    Crystal structures and other biochemical data indicate that the N-terminal cap (NCap) region of the Abelson tyrosine kinase (c-Abl) is important for maintaining the downregulated conformation of the kinase domain. The exact contributions that the NCap makes in stabilizing the various intramolecular interactions within c-Abl are less clear. While the NCap appears to be important for locking the SH3 and SH2 domains to the back of the kinase domain, there may be other more subtle elements of regulation. Hydrogen exchange (HX) and mass spectrometry (MS) were used to determine if the NCap contributes to intramolecular interactions involving the Abl SH3 domain. Under physiological conditions, the Abl SH3 domain underwent partial unfolding and its unfolding half-life was slowed during binding to the SH2 kinase linker, providing a unique assay for testing NCap-induced stabilization of the SH3 domain in various constructs. The results showed that the NCap stabilizes the dynamics of the SH3 domain in certain constructs but does not increase the relative affinity of the SH3 domain for the native SH2 kinase linker. The stabilization effect was absent in constructs of just the NCap and SH3 but was obvious when the SH2 domain and the SH2 kinase linker were present. These results suggest that interactions between the NCap and the SH3 domain can contribute to c-Abl stabilization in constructs that contain at least the SH2 domain, an effect that may partially compensate for the absence of the negative regulatory C-terminal tail found in the related Src family of kinases.

  19. Differential sensitivity of Src-family kinases to activation by SH3 domain displacement.

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    Jamie A Moroco

    Full Text Available Src-family kinases (SFKs are non-receptor protein-tyrosine kinases involved in a variety of signaling pathways in virtually every cell type. The SFKs share a common negative regulatory mechanism that involves intramolecular interactions of the SH3 domain with the PPII helix formed by the SH2-kinase linker as well as the SH2 domain with a conserved phosphotyrosine residue in the C-terminal tail. Growing evidence suggests that individual SFKs may exhibit distinct activation mechanisms dictated by the relative strengths of these intramolecular interactions. To elucidate the role of the SH3:linker interaction in the regulation of individual SFKs, we used a synthetic SH3 domain-binding peptide (VSL12 to probe the sensitivity of downregulated c-Src, Hck, Lyn and Fyn to SH3-based activation in a kinetic kinase assay. All four SFKs responded to VSL12 binding with enhanced kinase activity, demonstrating a conserved role for SH3:linker interaction in the control of catalytic function. However, the sensitivity and extent of SH3-based activation varied over a wide range. In addition, autophosphorylation of the activation loops of c-Src and Hck did not override regulatory control by SH3:linker displacement, demonstrating that these modes of activation are independent. Our results show that despite the similarity of their downregulated conformations, individual Src-family members show diverse responses to activation by domain displacement which may reflect their adaptation to specific signaling environments in vivo.

  20. Roles of the SH2 and SH3 domains in the regulation of neuronal Src kinase functions.

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    Groveman, Bradley R; Xue, Sheng; Marin, Vedrana; Xu, Jindong; Ali, Mohammad K; Bienkiewicz, Ewa A; Yu, Xian-Min

    2011-02-01

    Previous studies demonstrated that intra-domain interactions between Src family kinases (SFKs), stabilized by binding of the phosphorylated C-terminus to the SH2 domain and/or binding of the SH2 kinase linker to the SH3 domain, lock the molecules in a closed conformation, disrupt the kinase active site, and inactivate SFKs. Here we report that the up-regulation of N-methyl-D-aspartate receptors (NMDARs) induced by expression of constitutively active neuronal Src (n-Src), in which the C-terminus tyrosine is mutated to phenylalanine (n-Src/Y535F), is significantly reduced by dysfunctions of the SH2 and/or SH3 domains of the protein. Furthermore, we found that dysfunctions of SH2 and/or SH3 domains reduce auto-phosphorylation of the kinase activation loop, depress kinase activity, and decrease NMDAR phosphorylation. The SH2 domain plays a greater regulatory role than the SH3 domain. Our data also show that n-Src binds directly to the C-terminus of the NMDAR NR2A subunit in vitro, with a K(D) of 108.2 ± 13.3 nM. This binding is not Src kinase activity-dependent, and dysfunctions of the SH2 and/or SH3 domains do not significantly affect the binding. These data indicate that the SH2 and SH3 domains may function to promote the catalytic activity of active n-Src, which is important in the regulation of NMDAR functions. © 2010 The Authors Journal compilation © 2010 FEBS.

  1. Solution structure of the first SH3 domain of human vinexin and its interaction with vinculin peptides

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    Zhang, Jiahai; Li, Xiang; Yao, Bo; Shen, Weiqun; Sun, Hongbin; Xu, Chao; Wu, Jihui; Shi, Yunyu

    2007-01-01

    Solution structure of the first Src homology (SH) 3 domain of human vinexin (V S H3 1 ) was determined using nuclear magnetic resonance (NMR) method and revealed that it was a canonical SH3 domain, which has a typical β-β-β-β-α-β fold. Using chemical shift perturbation and surface plasmon resonance experiments, we studied the binding properties of the SH3 domain with two different peptides from vinculin hinge regions: P856 and P868. The observations illustrated slightly different affinities of the two peptides binding to V S H3 1 . The interaction between P868 and V S H3 1 belonged to intermediate exchange with a modest binding affinity, while the interaction between P856 and V S H3 1 had a low binding affinity. The structure and ligand-binding interface of V S H3 1 provide a structural basis for the further functional study of this important molecule

  2. Chemical shift assignments of the partially deuterated Fyn SH2-SH3 domain.

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    Kieken, Fabien; Loth, Karine; van Nuland, Nico; Tompa, Peter; Lenaerts, Tom

    2018-04-01

    Src Homology 2 and 3 (SH2 and SH3) are two key protein interaction modules involved in regulating the activity of many proteins such as tyrosine kinases and phosphatases by respective recognition of phosphotyrosine and proline-rich regions. In the Src family kinases, the inactive state of the protein is the direct result of the interaction of the SH2 and the SH3 domain with intra-molecular regions, leading to a closed structure incompetent with substrate modification. Here, we report the 1 H, 15 N and 13 C backbone- and side-chain chemical shift assignments of the partially deuterated Fyn SH3-SH2 domain and structural differences between tandem and single domains. The BMRB accession number is 27165.

  3. Computational analysis and prediction of the binding motif and protein interacting partners of the Abl SH3 domain.

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    Tingjun Hou

    2006-01-01

    Full Text Available Protein-protein interactions, particularly weak and transient ones, are often mediated by peptide recognition domains, such as Src Homology 2 and 3 (SH2 and SH3 domains, which bind to specific sequence and structural motifs. It is important but challenging to determine the binding specificity of these domains accurately and to predict their physiological interacting partners. In this study, the interactions between 35 peptide ligands (15 binders and 20 non-binders and the Abl SH3 domain were analyzed using molecular dynamics simulation and the Molecular Mechanics/Poisson-Boltzmann Solvent Area method. The calculated binding free energies correlated well with the rank order of the binding peptides and clearly distinguished binders from non-binders. Free energy component analysis revealed that the van der Waals interactions dictate the binding strength of peptides, whereas the binding specificity is determined by the electrostatic interaction and the polar contribution of desolvation. The binding motif of the Abl SH3 domain was then determined by a virtual mutagenesis method, which mutates the residue at each position of the template peptide relative to all other 19 amino acids and calculates the binding free energy difference between the template and the mutated peptides using the Molecular Mechanics/Poisson-Boltzmann Solvent Area method. A single position mutation free energy profile was thus established and used as a scoring matrix to search peptides recognized by the Abl SH3 domain in the human genome. Our approach successfully picked ten out of 13 experimentally determined binding partners of the Abl SH3 domain among the top 600 candidates from the 218,540 decapeptides with the PXXP motif in the SWISS-PROT database. We expect that this physical-principle based method can be applied to other protein domains as well.

  4. Effect of the SH3-SH2 domain linker sequence on the structure of Hck kinase.

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    Meiselbach, Heike; Sticht, Heinrich

    2011-08-01

    The coordination of activity in biological systems requires the existence of different signal transduction pathways that interact with one another and must be precisely regulated. The Src-family tyrosine kinases, which are found in many signaling pathways, differ in their physiological function despite their high overall structural similarity. In this context, the differences in the SH3-SH2 domain linkers might play a role for differential regulation, but the structural consequences of linker sequence remain poorly understood. We have therefore performed comparative molecular dynamics simulations of wildtype Hck and of a mutant Hck in which the SH3-SH2 domain linker is replaced by the corresponding sequence from the homologous kinase Lck. These simulations reveal that linker replacement not only affects the orientation of the SH3 domain itself, but also leads to an alternative conformation of the activation segment in the Hck kinase domain. The sequence of the SH3-SH2 domain linker thus exerts a remote effect on the active site geometry and might therefore play a role in modulating the structure of the inactive kinase or in fine-tuning the activation process itself.

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

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

    2006-01-01

    The crystal structure of the SH3 domain of human osteoclast-stimulating factor has been determined and refined to the ultrahigh resolution of 1.07 Å. The structure at atomic resolution provides an accurate framework for structure-based design of its inhibitors. Osteoclast-stimulating factor (OSF) is an intracellular signaling protein, produced by osteoclasts themselves, that enhances osteoclast formation and bone resorption. It is thought to act via an Src-related signaling pathway and contains SH3 and ankyrin-repeat domains which are involved in protein–protein interactions. As part of a structure-based anti-bone-loss drug-design program, the atomic resolution X-ray structure of the recombinant human OSF SH3 domain (hOSF-SH3) has been determined. The domain, residues 12–72, yielded crystals that diffracted to the ultrahigh resolution of 1.07 Å. The overall structure shows a characteristic SH3 fold consisting of two perpendicular β-sheets that form a β-barrel. Structure-based sequence alignment reveals that the putative proline-rich peptide-binding site of hOSF-SH3 consists of (i) residues that are highly conserved in the SH3-domain family, including residues Tyr21, Phe23, Trp49, Pro62, Asn64 and Tyr65, and (ii) residues that are less conserved and/or even specific to hOSF, including Thr22, Arg26, Thr27, Glu30, Asp46, Thr47, Asn48 and Leu60, which might be key to designing specific inhibitors for hOSF to fight osteoporosis and related bone-loss diseases. There are a total of 13 well defined water molecules forming hydrogen bonds with the above residues in and around the peptide-binding pocket. Some of those water molecules might be important for drug-design approaches. The hOSF-SH3 structure at atomic resolution provides an accurate framework for structure-based design of its inhibitors

  6. Abl N-terminal Cap stabilization of SH3 domain dynamics†

    OpenAIRE

    Chen, Shugui; Dumitrescu, Teodora Pene; Smithgall, Thomas E.; Engen, John R.

    2008-01-01

    Crystal structures and other biochemical data indicate that the N-terminal cap (NCap) region of the Abelson tyrosine kinase (c-Abl) is important for maintaining the downregulated conformation of the kinase domain. The exact contributions that NCap makes in stabilizing the various intramolecular interactions within c-Abl are less clear. While the NCap appears important for locking the SH3/SH2 domains to the back of the kinase domain, there may be other more subtle elements of regulation. Hydro...

  7. Molecular dynamics simulations from putative transition states of alpha-spectrin SH3 domain

    NARCIS (Netherlands)

    Periole, Xavier; Vendruscolo, Michele; Mark, Alan E.

    2007-01-01

    A series of molecular dynamics simulations in explicit solvent were started from nine structural models of the transition state of the SH3 domain of alpha-spectrin, which were generated by Lindorff Larsen et al. (Nat Struct Mol Biol 2004;11:443-449) using molecular dynamics simulations in which

  8. Insights into the folding and unfolding processes of wild-type and mutated SH3 domain by molecular dynamics and replica exchange molecular dynamics simulations.

    Directory of Open Access Journals (Sweden)

    Wen-Ting Chu

    Full Text Available Src-homology regions 3 (SH3 domain is essential for the down-regulation of tyrosine kinase activity. Mutation A39V/N53P/V55L of SH3 is found to be relative to the urgent misfolding diseases. To gain insight, the human and gallus SH3 domains (PDB ID: 1NYG and 2LP5, including 58 amino acids in each protein, were selected for MD simulations (Amber11, ff99SB force field and cluster analysis to investigate the influence of mutations on the spatial structure of the SH3 domain. It is found that the large conformational change of mutations mainly exists in three areas in the vicinity of protein core: RT loop, N-src loop, distal β-hairpin to 310 helix. The C-terminus of the mutated gallus SH3 is disordered after simulation, which represents the intermediate state of aggregation. The disappeared strong Hbond net in the mutated human and gallus systems will make these mutated proteins looser than the wild-type proteins. Additionally, by performing the REMD simulations on the gallus SH3 domain, the mutated domain is found to have an obvious effect on the unfolding process. These studies will be helpful for further aggregation mechanisms investigations on SH3 family.

  9. SH2 and SH3 domains: elements that control interactions of cytoplasmic signaling proteins.

    Science.gov (United States)

    Koch, C A; Anderson, D; Moran, M F; Ellis, C; Pawson, T

    1991-05-03

    Src homology (SH) regions 2 and 3 are noncatalytic domains that are conserved among a series of cytoplasmic signaling proteins regulated by receptor protein-tyrosine kinases, including phospholipase C-gamma, Ras GTPase (guanosine triphosphatase)-activating protein, and Src-like tyrosine kinases. The SH2 domains of these signaling proteins bind tyrosine phosphorylated polypeptides, implicated in normal signaling and cellular transformation. Tyrosine phosphorylation acts as a switch to induce the binding of SH2 domains, thereby mediating the formation of heteromeric protein complexes at or near the plasma membrane. The formation of these complexes is likely to control the activation of signal transduction pathways by tyrosine kinases. The SH3 domain is a distinct motif that, together with SH2, may modulate interactions with the cytoskeleton and membrane. Some signaling and transforming proteins contain SH2 and SH3 domains unattached to any known catalytic element. These noncatalytic proteins may serve as adaptors to link tyrosine kinases to specific target proteins. These observations suggest that SH2 and SH3 domains participate in the control of intracellular responses to growth factor stimulation.

  10. Rhodium(II) metallopeptide catalyst design enables fine control in selective functionalization of natural SH3 domains.

    Science.gov (United States)

    Vohidov, Farrukh; Coughlin, Jane M; Ball, Zachary T

    2015-04-07

    Chemically modified proteins are increasingly important for use in fundamental biophysical studies, chemical biology, therapeutic protein development, and biomaterials. However, chemical methods typically produce heterogeneous labeling and cannot approach the exquisite selectivity of enzymatic reactions. While bioengineered methods are sometimes an option, selective reactions of natural proteins remain an unsolved problem. Here we show that rhodium(II) metallopeptides combine molecular recognition with promiscuous catalytic activity to allow covalent decoration of natural SH3 domains, depending on choice of catalyst but independent of the specific residue present. A metallopeptide catalyst succeeds in modifying a single SH3-containing kinase at endogenous concentrations in prostate cancer (PC-3) cell lysate. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Regulation of the interaction between the neuronal BIN1 isoform 1 and Tau proteins - role of the SH3 domain.

    Science.gov (United States)

    Malki, Idir; Cantrelle, François-Xavier; Sottejeau, Yoann; Lippens, Guy; Lambert, Jean-Charles; Landrieu, Isabelle

    2017-10-01

    Bridging integrator 1 (bin1) gene is a genetic determinant of Alzheimer's disease (AD) and has been reported to modulate Alzheimer's pathogenesis through pathway(s) involving Tau. The functional impact of Tau/BIN1 interaction as well as the molecular details of this interaction are still not fully resolved. As a consequence, how BIN1 through its interaction with Tau affects AD risk is also still not determined. To progress in this understanding, interaction of Tau with two BIN1 isoforms was investigated using Nuclear Magnetic Resonance spectroscopy. 1 H, 15 N spectra showed that the C-terminal SH3 domain of BIN1 isoform 1 (BIN1Iso1) is not mobile in solution but locked with the core of the protein. In contrast, the SH3 domain of BIN1 isoform 9 (BIN1Iso9) behaves as an independent mobile domain. This reveals an equilibrium between close and open conformations for the SH3 domain. Interestingly, a 334-376 peptide from the clathrin and AP-2-binding domain (CLAP) domain of BIN1Iso1, which contains a SH3-binding site, is able to compete with BIN1-SH3 intramolecular interaction. For both BIN1 isoforms, the SH3 domain can interact with Tau(210-240) sequence. Tau(210-240) peptide can indeed displace the intramolecular interaction of the BIN1-SH3 of BIN1Iso1 and form a complex with the released domain. The measured K d were in agreement with a stronger affinity of Tau peptide. Both CLAP and Tau peptides occupied the same surface on the BIN1-SH3 domain, showing that their interaction is mutually exclusive. These results emphasize an additional level of complexity in the regulation of the interaction between BIN1 and Tau dependent of the BIN1 isoforms. © 2017 Federation of European Biochemical Societies.

  12. Association between receptor protein-tyrosine phosphatase RPTPalpha and the Grb2 adaptor. Dual Src homology (SH) 2/SH3 domain requirement and functional consequences

    DEFF Research Database (Denmark)

    Su, J; Yang, L T; Sap, J

    1996-01-01

    domain in Grb2 (, ). We show here that association of Grb2 with RPTPalpha also involves a critical function for the C-terminal SH3 domain of Grb2. Furthermore, Grb2 SH3 binding peptides interfere with RPTPalpha-Grb2 association in vitro, and the RPTPalpha protein can dissociate the Grb2-Sos complex...... in vivo. These observations constitute a novel mode of Grb2 association and suggest a model in which association with a tyrosine-phosphorylated protein restricts the repertoire of SH3 binding proteins with which Grb2 can simultaneously interact. The function of the Tyr798 tyrosine phosphorylation/Grb2...... binding site in RPTPalpha was studied further by expression of wild type or mutant RPTPalpha proteins in PC12 cells. In these cells, wild type RPTPalpha interferes with acidic fibroblast growth factor-induced neurite outgrowth; this effect requires both the catalytic activity and the Grb2 binding Tyr798...

  13. SH3 domain-mediated recruitment of host cell amphiphysins by alphavirus nsP3 promotes viral RNA replication.

    Directory of Open Access Journals (Sweden)

    Maarit Neuvonen

    2011-11-01

    Full Text Available Among the four non-structural proteins of alphaviruses the function of nsP3 is the least well understood. NsP3 is a component of the viral replication complex, and composed of a conserved aminoterminal macro domain implicated in viral RNA synthesis, and a poorly conserved carboxyterminal region. Despite the lack of overall homology we noted a carboxyterminal proline-rich sequence motif shared by many alphaviral nsP3 proteins, and found it to serve as a preferred target site for the Src-homology 3 (SH3 domains of amphiphysin-1 and -2. Nsp3 proteins of Semliki Forest (SFV, Sindbis (SINV, and Chikungunya viruses all showed avid and SH3-dependent binding to amphiphysins. Upon alphavirus infection the intracellular distribution of amphiphysin was dramatically altered and colocalized with nsP3. Mutations in nsP3 disrupting the amphiphysin SH3 binding motif as well as RNAi-mediated silencing of amphiphysin-2 expression resulted in impaired viral RNA replication in HeLa cells infected with SINV or SFV. Infection of Balb/c mice with SFV carrying an SH3 binding-defective nsP3 was associated with significantly decreased mortality. These data establish SH3 domain-mediated binding of nsP3 with amphiphysin as an important host cell interaction promoting alphavirus replication.

  14. Crystal structure of Src-like adaptor protein 2 reveals close association of SH3 and SH2 domains through β-sheet formation.

    Science.gov (United States)

    Wybenga-Groot, Leanne E; McGlade, C Jane

    2013-12-01

    The Src-like adaptor proteins (SLAP/SLAP2) are key components of Cbl-dependent downregulation of antigen receptor, cytokine receptor, and receptor tyrosine kinase signaling in hematopoietic cells. SLAP and SLAP2 consist of adjacent SH3 and SH2 domains that are most similar in sequence to Src family kinases (SFKs). Notably, the SH3-SH2 connector sequence is significantly shorter in SLAP/SLAP2 than in SFKs. To understand the structural implication of a short SH3-SH2 connector sequence, we solved the crystal structure of a protein encompassing the SH3 domain, SH3-SH2 connector, and SH2 domain of SLAP2 (SLAP2-32). While both domains adopt typical folds, the short SH3-SH2 connector places them in close association. Strand βe of the SH3 domain interacts with strand βA of the SH2 domain, resulting in the formation of a continuous β sheet that spans the length of the protein. Disruption of the SH3/SH2 interface through mutagenesis decreases SLAP-32 stability in vitro, consistent with inter-domain binding being an important component of SLAP2 structure and function. The canonical peptide binding pockets of the SH3 and SH2 domains are fully accessible, in contrast to other protein structures that display direct interaction between SH3 and SH2 domains, in which either peptide binding surface is obstructed by the interaction. Our results reveal potential sites of novel interaction for SH3 and SH2 domains, and illustrate the adaptability of SH2 and SH3 domains in mediating interactions. As well, our results suggest that the SH3 and SH2 domains of SLAP2 function interdependently, with implications on their mode of substrate binding. © 2013.

  15. Expression, refolding and crystallizations of the Grb2-like (GADS) C-terminal SH3 domain complexed with a SLP-76 motif peptide

    International Nuclear Information System (INIS)

    Faravelli, Alessandro; Dimasi, Nazzareno

    2005-01-01

    Several crystals of the Grb2-like C-terminal SH3 domain in complex with a motif peptide from the SLP-76 protein were obtained and characterized. The Grb2-like adaptor protein GADS is composed of an N-terminal SH3 domain, an SH2 domain, a proline-rich region and a C-terminal SH3 domain. GADS interacts through its C-terminal SH3 domain with the adaptor protein SLP-76, thus recruiting this protein and other associated molecules to the linker for activation of T-cell (LAT) protein. The DNA encoding the C-terminal SH3 domain of GADS (GADS-cSH3) was assembled synthetically using a recursive PCR technique and the protein was overexpressed in Escherichia coli, refolded and purified. Several crystals of this domain in complex with the SLP-76 peptide were obtained and characterized

  16. Linker length dependent binding of a focal adhesion kinase derived peptide to the Src SH3-SH2 domains.

    Science.gov (United States)

    Lindfors, Hanna E; Venkata, Bharat Somireddy; Drijfhout, Jan W; Ubbink, Marcellus

    2011-02-18

    The interaction between a peptide encompassing the SH3 and SH2 binding motifs of focal adhesion kinase (FAK) and the Src SH3-SH2 domains has been investigated with NMR spectroscopy and calorimetry. The binding to both motifs is anti-cooperative. Reduction of the long linker connecting the motifs does not lead to cooperativity. Short linkers that do not allow simultaneous intramolecular binding of the peptide to both motifs cause peptide-mediated dimerisation, even with a linker of only three amino acids. The role of the SH3 binding motif is discussed in view of the independent nature of the SH interactions. Copyright © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Qingping; Mengin-Lecreulx, Dominique; Liu, Xueqian W.; Patin, Delphine; Farr, Carol L.; Grant, Joanna C.; Chiu, Hsiu-Ju; Jaroszewski, Lukasz; Knuth, Mark W.; Godzik, Adam; Lesley, Scott A.; Elsliger, Marc-André; Deacon, Ashley M.; Wilson, Ian A.

    2015-09-15

    ABSTRACT

    Bacterial SH3 (SH3b) domains are commonly fused with papain-like Nlp/P60 cell wall hydrolase domains. To understand how the modular architecture of SH3b and NlpC/P60 affects the activity of the catalytic domain, three putative NlpC/P60 cell wall hydrolases were biochemically and structurally characterized. These enzymes all have γ-d-Glu-A2pm (A2pm is diaminopimelic acid) cysteine amidase (ordl-endopeptidase) activities but with different substrate specificities. One enzyme is a cell wall lysin that cleaves peptidoglycan (PG), while the other two are cell wall recycling enzymes that only cleave stem peptides with an N-terminall-Ala. Their crystal structures revealed a highly conserved structure consisting of two SH3b domains and a C-terminal NlpC/P60 catalytic domain, despite very low sequence identity. Interestingly, loops from the first SH3b domain dock into the ends of the active site groove of the catalytic domain, remodel the substrate binding site, and modulate substrate specificity. Two amino acid differences at the domain interface alter the substrate binding specificity in favor of stem peptides in recycling enzymes, whereas the SH3b domain may extend the peptidoglycan binding surface in the cell wall lysins. Remarkably, the cell wall lysin can be converted into a recycling enzyme with a single mutation.

    IMPORTANCEPeptidoglycan is a meshlike polymer that envelops the bacterial plasma membrane and bestows structural integrity. Cell wall lysins and recycling enzymes are part of a set of lytic enzymes that target covalent bonds connecting the amino acid and amino sugar building blocks of the PG network. These hydrolases are involved in processes such as cell growth and division, autolysis, invasion, and PG turnover and recycling. To avoid cleavage of unintended substrates, these enzymes have very selective substrate specificities. Our biochemical and structural

  18. Expression, purification, crystallization and preliminary X-ray crystallographic analysis of the SH3 domain of human AHI1

    International Nuclear Information System (INIS)

    Shi, Zhuliang; Liang, Ning; Xu, Wei; Li, Kuai; Sheng, Guoqing; Liu, Jinsong; Xu, Aimin; Li, Xiao-Jiang; Wu, Donghai

    2009-01-01

    The SH3 domain of human AHI1 has been cloned and expressed in Escherichia coli. The protein was purified by affinity and size-exclusion chromatography and was crystallized using the sitting-drop vapour-diffusion method at 293 K. The SH3 domain of human AHI1 was cloned and expressed in Escherichia coli. The protein was purified by affinity and size-exclusion chromatography and was crystallized using the sitting-drop vapour-diffusion method at 293 K. A complete data set was collected to 2.5 Å resolution at 110 K. The crystal belonged to space group P4 1 2 1 2, with unit-cell parameters a = 67.377, b = 67.377, c = 98.549 Å

  19. Binding of the cSH3 domain of Grb2 adaptor to two distinct RXXK motifs within Gab1 docker employs differential mechanisms.

    Science.gov (United States)

    McDonald, Caleb B; Seldeen, Kenneth L; Deegan, Brian J; Bhat, Vikas; Farooq, Amjad

    2011-01-01

    A ubiquitous component of cellular signaling machinery, Gab1 docker plays a pivotal role in routing extracellular information in the form of growth factors and cytokines to downstream targets such as transcription factors within the nucleus. Here, using isothermal titration calorimetry (ITC) in combination with macromolecular modeling (MM), we show that although Gab1 contains four distinct RXXK motifs, designated G1, G2, G3, and G4, only G1 and G2 motifs bind to the cSH3 domain of Grb2 adaptor and do so with distinct mechanisms. Thus, while the G1 motif strictly requires the PPRPPKP consensus sequence for high-affinity binding to the cSH3 domain, the G2 motif displays preference for the PXVXRXLKPXR consensus. Such sequential differences in the binding of G1 and G2 motifs arise from their ability to adopt distinct polyproline type II (PPII)- and 3(10) -helical conformations upon binding to the cSH3 domain, respectively. Collectively, our study provides detailed biophysical insights into a key protein-protein interaction involved in a diverse array of signaling cascades central to health and disease. Copyright © 2010 John Wiley & Sons, Ltd.

  20. A graph kernel approach for alignment-free domain-peptide interaction prediction with an application to human SH3 domains.

    Science.gov (United States)

    Kundu, Kousik; Costa, Fabrizio; Backofen, Rolf

    2013-07-01

    State-of-the-art experimental data for determining binding specificities of peptide recognition modules (PRMs) is obtained by high-throughput approaches like peptide arrays. Most prediction tools applicable to this kind of data are based on an initial multiple alignment of the peptide ligands. Building an initial alignment can be error-prone, especially in the case of the proline-rich peptides bound by the SH3 domains. Here, we present a machine-learning approach based on an efficient graph-kernel technique to predict the specificity of a large set of 70 human SH3 domains, which are an important class of PRMs. The graph-kernel strategy allows us to (i) integrate several types of physico-chemical information for each amino acid, (ii) consider high-order correlations between these features and (iii) eliminate the need for an initial peptide alignment. We build specialized models for each human SH3 domain and achieve competitive predictive performance of 0.73 area under precision-recall curve, compared with 0.27 area under precision-recall curve for state-of-the-art methods based on position weight matrices. We show that better models can be obtained when we use information on the noninteracting peptides (negative examples), which is currently not used by the state-of-the art approaches based on position weight matrices. To this end, we analyze two strategies to identify subsets of high confidence negative data. The techniques introduced here are more general and hence can also be used for any other protein domains, which interact with short peptides (i.e. other PRMs). The program with the predictive models can be found at http://www.bioinf.uni-freiburg.de/Software/SH3PepInt/SH3PepInt.tar.gz. We also provide a genome-wide prediction for all 70 human SH3 domains, which can be found under http://www.bioinf.uni-freiburg.de/Software/SH3PepInt/Genome-Wide-Predictions.tar.gz. Supplementary data are available at Bioinformatics online.

  1. The SH2 and SH3 domains of mammalian Grb2 couple the EGF receptor to the Ras activator mSos1.

    Science.gov (United States)

    Rozakis-Adcock, M; Fernley, R; Wade, J; Pawson, T; Bowtell, D

    1993-05-06

    Many tyrosine kinases, including the receptors for hormones such as epidermal growth factor (EGF), nerve growth factor and insulin, transmit intracellular signals through Ras proteins. Ligand binding to such receptors stimulates Ras guanine-nucleotide-exchange activity and increases the level of GTP-bound Ras, suggesting that these tyrosine kinases may activate a guanine-nucleotide releasing protein (GNRP). In Caenorhabditis elegans and Drosophila, genetic studies have shown that Ras activation by tyrosine kinases requires the protein Sem-5/drk, which contains a single Src-homology (SH) 2 domain and two flanking SH3 domains. Sem-5 is homologous to the mammalian protein Grb2, which binds the autophosphorylated EGF receptor and other phosphotyrosine-containing proteins such as Shc through its SH2 domain. Here we show that in rodent fibroblasts, the SH3 domains of Grb2 are bound to the proline-rich carboxy-terminal tail of mSos1, a protein homologous to Drosophila Sos. Sos is required for Ras signalling and contains a central domain related to known Ras-GNRPs. EGF stimulation induces binding of the Grb2-mSos1 complex to the autophosphorylated EGF receptor, and mSos1 phosphorylation. Grb2 therefore appears to link tyrosine kinases to a Ras-GNRP in mammalian cells.

  2. Complex formation of EphB1/Nck/Caskin1 leads to tyrosine phosphorylation and structural changes of the Caskin1 SH3 domain

    Directory of Open Access Journals (Sweden)

    Pesti Szabolcs

    2012-11-01

    Full Text Available Abstract Background Scaffold proteins have an important role in the regulation of signal propagation. These proteins do not possess any enzymatic activity but can contribute to the formation of multiprotein complexes. Although scaffold proteins are present in all cell types, the nervous system contains them in the largest amount. Caskin proteins are typically present in neuronal cells, particularly, in the synapses. However, the signaling mechanisms by which Caskin proteins are regulated are largely unknown. Results Here we demonstrate that EphB1 receptor tyrosine kinase can recruit Caskin1 through the adaptor protein Nck. Upon activation of the receptor kinase, the SH2 domain of Nck binds to one of its tyrosine residues, while Nck SH3 domains interact with the proline-rich domain of Caskin1. Complex formation of the receptor, adaptor and scaffold proteins results in the tyrosine phosphorylation of Caskin1 on its SH3 domain. The phosphorylation sites were identified by mass-spectrometry as tyrosines 296 and 336. To reveal the structural consequence of this phosphorylation, CD spectroscopy was performed. This measurement suggests that upon tyrosine phosphorylation the structure of the Caskin1 SH3 domain changes significantly. Conclusion Taken together, we propose that the scaffold protein Caskin1 can form a complex with the EphB1 tyrosine kinase via the Nck protein as a linker. Complex formation results in tyrosine phosphorylation of the Caskin1 SH3 domain. Although we were not able to identify any physiological partner of the SH3 domain so far, we could demonstrate that phosphorylation on conserved tyrosine residues results in marked changes in the structure of the SH3 domain.

  3. Physical and functional interactions between SH2 and SH3 domains of the Src family protein tyrosine kinase p59fyn

    NARCIS (Netherlands)

    Panchamoorthy, G.; Fukazawa, T.; Stolz, L.; Payne, G.; Reedquist, K.; Shoelson, S.; Songyang, Z.; Cantley, L.; Walsh, C.; Band, H.

    1994-01-01

    The Src family protein tyrosine kinases participate in signalling through cell surface receptors that lack intrinsic tyrosine kinase domains. All nine members of this family possess adjacent Src homology (SH2 and SH3) domains, both of which are essential for repression of the enzymatic activity. The

  4. Mutation of CD2AP and SH3KBP1 Binding Motif in Alphavirus nsP3 Hypervariable Domain Results in Attenuated Virus

    Directory of Open Access Journals (Sweden)

    Margit Mutso

    2018-04-01

    Full Text Available Infection by Chikungunya virus (CHIKV of the Old World alphaviruses (family Togaviridae in humans can cause arthritis and arthralgia. The virus encodes four non-structural proteins (nsP (nsP1, nsp2, nsP3 and nsP4 that act as subunits of the virus replicase. These proteins also interact with numerous host proteins and some crucial interactions are mediated by the unstructured C-terminal hypervariable domain (HVD of nsP3. In this study, a human cell line expressing EGFP tagged with CHIKV nsP3 HVD was established. Using quantitative proteomics, it was found that CHIKV nsP3 HVD can bind cytoskeletal proteins, including CD2AP, SH3KBP1, CAPZA1, CAPZA2 and CAPZB. The interaction with CD2AP was found to be most evident; its binding site was mapped to the second SH3 ligand-like element in nsP3 HVD. Further assessment indicated that CD2AP can bind to nsP3 HVDs of many different New and Old World alphaviruses. Mutation of the short binding element hampered the ability of the virus to establish infection. The mutation also abolished ability of CD2AP to co-localise with nsP3 and replication complexes of CHIKV; the same was observed for Semliki Forest virus (SFV harbouring a similar mutation. Similar to CD2AP, its homolog SH3KBP1 also bound the identified motif in CHIKV and SFV nsP3.

  5. Mutation of CD2AP and SH3KBP1 Binding Motif in Alphavirus nsP3 Hypervariable Domain Results in Attenuated Virus.

    Science.gov (United States)

    Mutso, Margit; Morro, Ainhoa Moliner; Smedberg, Cecilia; Kasvandik, Sergo; Aquilimeba, Muriel; Teppor, Mona; Tarve, Liisi; Lulla, Aleksei; Lulla, Valeria; Saul, Sirle; Thaa, Bastian; McInerney, Gerald M; Merits, Andres; Varjak, Margus

    2018-04-27

    Infection by Chikungunya virus (CHIKV) of the Old World alphaviruses (family Togaviridae) in humans can cause arthritis and arthralgia. The virus encodes four non-structural proteins (nsP) (nsP1, nsp2, nsP3 and nsP4) that act as subunits of the virus replicase. These proteins also interact with numerous host proteins and some crucial interactions are mediated by the unstructured C-terminal hypervariable domain (HVD) of nsP3. In this study, a human cell line expressing EGFP tagged with CHIKV nsP3 HVD was established. Using quantitative proteomics, it was found that CHIKV nsP3 HVD can bind cytoskeletal proteins, including CD2AP, SH3KBP1, CAPZA1, CAPZA2 and CAPZB. The interaction with CD2AP was found to be most evident; its binding site was mapped to the second SH3 ligand-like element in nsP3 HVD. Further assessment indicated that CD2AP can bind to nsP3 HVDs of many different New and Old World alphaviruses. Mutation of the short binding element hampered the ability of the virus to establish infection. The mutation also abolished ability of CD2AP to co-localise with nsP3 and replication complexes of CHIKV; the same was observed for Semliki Forest virus (SFV) harbouring a similar mutation. Similar to CD2AP, its homolog SH3KBP1 also bound the identified motif in CHIKV and SFV nsP3.

  6. SH3 domain-mediated binding of the Drk protein to Dos is an important step in signaling of Drosophila receptor tyrosine kinases.

    Science.gov (United States)

    Feller, Stephan M; Wecklein, Heike; Lewitzky, Marc; Kibler, Eike; Raabe, Thomas

    2002-08-01

    Activation of the Sevenless (Sev) receptor tyrosine kinase (RTK) in the developing Drosophila eye is required for the specification of the R7 photoreceptor cell fate. Daughter of Sevenless (Dos), a putative multi-site adaptor protein, is a substrate of the Sev kinase and is known to associate with the tyrosine phosphatase Corkscrew (Csw). Binding of Csw to Dos depends on the Csw Src homology 2 (SH2) domains and is an essential step for signaling by the Sev RTK. Dos, however, lacks a recognizable phosphotyrosine interaction domain and it was previously unclear how it is recruited to the Sev receptor. Here it is shown that the SH2/SH3 domain adaptor protein Drk can provide this link. Drk binds with its SH2 domain to the autophosphorylated Sev receptor while the C-terminal SH3 domain is able to associate with Dos. The Drk SH3 domain binding motifs on Dos were mapped to two sites which do not conform the known Drk SH3 domain binding motif (PxxPxR) but instead have the consensus PxxxRxxKP. Mutational analysis in vitro and in vivo provided evidence that both Drk binding sites fulfil an important function in the context of Sev and Drosophila epidermal growth factor receptor mediated signaling processes.

  7. Analysis of the thermodynamics of binding of an SH3 domain to proline-rich peptides using a chimeric fusion protein.

    Science.gov (United States)

    Candel, Adela M; van Nuland, Nico A J; Martin-Sierra, Francisco M; Martinez, Jose C; Conejero-Lara, Francisco

    2008-03-14

    A complete understanding of the thermodynamic determinants of binding between SH3 domains and proline-rich peptides is crucial to the development of rational strategies for designing ligands for these important domains. Recently we engineered a single-chain chimeric protein by fusing the alpha-spectrin Src homology region 3 (SH3) domain to the decapeptide APSYSPPPPP (p41). This chimera mimics the structural and energetic features of the interaction between SH3 domains and proline-rich peptides. Here we show that analysing the unfolding thermodynamics of single-point mutants of this chimeric fusion protein constitutes a very useful approach to deciphering the thermodynamics of SH3-ligand interactions. To this end, we investigated the contribution of each proline residue of the ligand sequence to the SH3-peptide interaction by producing six single Pro-Ala mutants of the chimeric protein and analysing their unfolding thermodynamics by differential scanning calorimetry (DSC). Structural analyses of the mutant chimeras by circular dichroism, fluorescence and NMR together with NMR-relaxation measurements indicate conformational flexibility at the binding interface, which is strongly affected by the different Pro-Ala mutations. An analysis of the DSC thermograms on the basis of a three-state unfolding model has allowed us to distinguish and separate the thermodynamic magnitudes of the interaction at the binding interface. The model assumes equilibrium between the "unbound" and "bound" states at the SH3-peptide binding interface. The resulting thermodynamic magnitudes classify the different proline residues according to their importance in the interaction as P2 approximately P7 approximately P10>P9 approximately P6>P8, which agrees well with Lim's model for the interaction between SH3 domains and proline-rich peptides. In addition, the thermodynamic signature of the interaction is the same as that usually found for this type of binding, with a strong enthalpy

  8. Artificial proteins as allosteric modulators of PDZ3 and SH3 in two-domain constructs: A computational characterization of novel chimeric proteins

    Czech Academy of Sciences Publication Activity Database

    Palani, K.; Pfeiferová, L.; Boušová, Kristýna; Bednárová, L.; Obšilová, Veronika; Vondrášek, J.

    2016-01-01

    Roč. 84, č. 10 (2016), s. 1358-1374 ISSN 0887-3585 Institutional support: RVO:67985823 Keywords : protein design * fusion proteins * PDZ3 * SH3 * Trp-cage * two domain proteins * molecular dynamics simulation * circular dichroism Subject RIV: BO - Biophysics Impact factor: 2.289, year: 2016

  9. Artificial proteins as allosteric modulators of PDZ3 and SH3 in two-domain constructs: A computational characterization of novel chimeric proteins

    Czech Academy of Sciences Publication Activity Database

    Palani, Kirubakaran; Pfeiferová, Lucie; Boušová, Kristýna; Bednárová, Lucie; Obšilová, V.; Vondrášek, Jiří

    2016-01-01

    Roč. 84, č. 10 (2016), s. 1358-1374 ISSN 0887-3585 Institutional support: RVO:61388963 Keywords : protein design * fusion proteins * PDZ3 * SH3 * Trp-cage * two domain proteins Subject RIV: CE - Biochemistry Impact factor: 2.289, year: 2016

  10. Thermodynamic dissection of the binding energetics of proline-rich peptides to the Abl-SH3 domain: implications for rational ligand design.

    Science.gov (United States)

    Palencia, Andrés; Cobos, Eva S; Mateo, Pedro L; Martínez, Jose C; Luque, Irene

    2004-02-13

    The inhibition of the interactions between SH3 domains and their targets is emerging as a promising therapeutic strategy. To date, rational design of potent ligands for these domains has been hindered by the lack of understanding of the origins of the binding energy. We present here a complete thermodynamic analysis of the binding energetics of the p41 proline-rich decapeptide (APSYSPPPPP) to the SH3 domain of the c-Abl oncogene. Isothermal titration calorimetry experiments have revealed a thermodynamic signature for this interaction (very favourable enthalpic contributions opposed by an unfavourable binding entropy) inconsistent with the highly hydrophobic nature of the p41 ligand and the Abl-SH3 binding site. Our structural and thermodynamic analyses have led us to the conclusion, having once ruled out any possible ionization events or conformational changes coupled to the association, that the establishment of a complex hydrogen-bond network mediated by water molecules buried at the binding interface is responsible for the observed thermodynamic behaviour. The origin of the binding energetics for proline-rich ligands to the Abl-SH3 domain is further investigated by a comparative calorimetric analysis of a set of p41-related ligands. The striking effects upon the enthalpic and entropic contributions provoked by conservative substitutions at solvent-exposed positions in the ligand confirm the complexity of the interaction. The implications of these results for rational ligand design are discussed.

  11. A graph kernel approach for alignment-free domain–peptide interaction prediction with an application to human SH3 domains

    Science.gov (United States)

    Kundu, Kousik; Costa, Fabrizio; Backofen, Rolf

    2013-01-01

    Motivation: State-of-the-art experimental data for determining binding specificities of peptide recognition modules (PRMs) is obtained by high-throughput approaches like peptide arrays. Most prediction tools applicable to this kind of data are based on an initial multiple alignment of the peptide ligands. Building an initial alignment can be error-prone, especially in the case of the proline-rich peptides bound by the SH3 domains. Results: Here, we present a machine-learning approach based on an efficient graph-kernel technique to predict the specificity of a large set of 70 human SH3 domains, which are an important class of PRMs. The graph-kernel strategy allows us to (i) integrate several types of physico-chemical information for each amino acid, (ii) consider high-order correlations between these features and (iii) eliminate the need for an initial peptide alignment. We build specialized models for each human SH3 domain and achieve competitive predictive performance of 0.73 area under precision-recall curve, compared with 0.27 area under precision-recall curve for state-of-the-art methods based on position weight matrices. We show that better models can be obtained when we use information on the noninteracting peptides (negative examples), which is currently not used by the state-of-the art approaches based on position weight matrices. To this end, we analyze two strategies to identify subsets of high confidence negative data. The techniques introduced here are more general and hence can also be used for any other protein domains, which interact with short peptides (i.e. other PRMs). Availability: The program with the predictive models can be found at http://www.bioinf.uni-freiburg.de/Software/SH3PepInt/SH3PepInt.tar.gz. We also provide a genome-wide prediction for all 70 human SH3 domains, which can be found under http://www.bioinf.uni-freiburg.de/Software/SH3PepInt/Genome-Wide-Predictions.tar.gz. Contact: backofen@informatik.uni-freiburg.de Supplementary

  12. Disruption of Fyn SH3 domain interaction with a proline-rich motif in liver kinase B1 results in activation of AMP-activated protein kinase.

    Directory of Open Access Journals (Sweden)

    Eijiro Yamada

    Full Text Available Fyn-deficient mice display increased AMP-activated Protein Kinase (AMPK activity as a result of Fyn-dependent regulation of Liver Kinase B1 (LKB1 in skeletal muscle. Mutation of Fyn-specific tyrosine sites in LKB1 results in LKB1 export into the cytoplasm and increased AMPK activation site phosphorylation. This study characterizes the structural elements responsible for the physical interaction between Fyn and LKB1. Effects of point mutations in the Fyn SH2/SH3 domains and in the LKB1 proline-rich motif on 1 Fyn and LKB1 binding, 2 LKB1 subcellular localization and 3 AMPK phosphorylation were investigated in C2C12 muscle cells. Additionally, novel LKB1 proline-rich motif mimicking cell permeable peptides were generated to disrupt Fyn/LKB1 binding and investigate the consequences on AMPK activity in both C2C12 cells and mouse skeletal muscle. Mutation of either Fyn SH3 domain or the proline-rich motif of LKB1 resulted in the disruption of Fyn/LKB1 binding, re-localization of 70% of LKB1 signal in the cytoplasm and a 2-fold increase in AMPK phosphorylation. In vivo disruption of the Fyn/LKB1 interaction using LKB1 proline-rich motif mimicking cell permeable peptides recapitulated Fyn pharmacological inhibition. We have pinpointed the structural elements within Fyn and LKB1 that are responsible for their binding, demonstrating the functionality of this interaction in regulating AMPK activity.

  13. Comparison of the frequency of functional SH3 domains with different limited sets of amino acids using mRNA display.

    Directory of Open Access Journals (Sweden)

    Junko Tanaka

    Full Text Available Although modern proteins consist of 20 different amino acids, it has been proposed that primordial proteins consisted of a small set of amino acids, and additional amino acids have gradually been recruited into the genetic code. This hypothesis has recently been supported by comparative genome sequence analysis, but no direct experimental approach has been reported. Here, we utilized a novel experimental approach to test a hypothesis that native-like globular proteins might be easily simplified by a set of putative primitive amino acids with retention of its structure and function than by a set of putative new amino acids. We performed in vitro selection of a functional SH3 domain as a model from partially randomized libraries with different sets of amino acids using mRNA display. Consequently, a library rich in putative primitive amino acids included a larger number of functional SH3 sequences than a library rich in putative new amino acids. Further, the functional SH3 sequences were enriched from the primitive library slightly earlier than from a randomized library with the full set of amino acids, while the function and structure of the selected SH3 proteins with the primitive alphabet were comparable with those from the 20 amino acid alphabet. Application of this approach to various combinations of codons in protein sequences may be useful not only for clarifying the precise order of the amino acid expansion in the early stages of protein evolution but also for efficiently creating novel functional proteins in the laboratory.

  14. Electrostatic effects in the folding of the SH3 domain of the c-Src tyrosine kinase: pH-dependence in 3D-domain swapping and amyloid formation.

    Directory of Open Access Journals (Sweden)

    Julio Bacarizo

    Full Text Available The SH3 domain of the c-Src tyrosine kinase (c-Src-SH3 aggregates to form intertwined dimers and amyloid fibrils at mild acid pHs. In this work, we show that a single mutation of residue Gln128 of this SH3 domain has a significant effect on: (i its thermal stability; and (ii its propensity to form amyloid fibrils. The Gln128Glu mutant forms amyloid fibrils at neutral pH but not at mild acid pH, while Gln128Lys and Gln128Arg mutants do not form these aggregates under any of the conditions assayed. We have also solved the crystallographic structures of the wild-type (WT and Gln128Glu, Gln128Lys and Gln128Arg mutants from crystals obtained at different pHs. At pH 5.0, crystals belong to the hexagonal space group P6₅22 and the asymmetric unit is formed by one chain of the protomer of the c-Src-SH3 domain in an open conformation. At pH 7.0, crystals belong to the orthorhombic space group P2₁2₁2₁, with two molecules at the asymmetric unit showing the characteristic fold of the SH3 domain. Analysis of these crystallographic structures shows that the residue at position 128 is connected to Glu106 at the diverging β-turn through a cluster of water molecules. Changes in this hydrogen-bond network lead to the displacement of the c-Src-SH3 distal loop, resulting also in conformational changes of Leu100 that might be related to the binding of proline rich motifs. Our findings show that electrostatic interactions and solvation of residues close to the folding nucleation site of the c-Src-SH3 domain might play an important role during the folding reaction and the amyloid fibril formation.

  15. The C-terminus SH3-binding domain of Kv1.3 is required for the actin-mediated immobilization of the channel via cortactin

    Science.gov (United States)

    Hajdu, Peter; Martin, Geoffrey V.; Chimote, Ameet A.; Szilagyi, Orsolya; Takimoto, Koichi; Conforti, Laura

    2015-01-01

    Kv1.3 channels play a pivotal role in the activation and migration of T-lymphocytes. These functions are accompanied by the channels' polarization, which is essential for associated downstream events. However, the mechanisms that govern the membrane movement of Kv1.3 channels remain unclear. F-actin polymerization occurs concomitantly to channel polarization, implicating the actin cytoskeleton in this process. Here we show that cortactin, a factor initiating the actin network, controls the membrane mobilization of Kv1.3 channels. FRAP with EGFP-tagged Kv1.3 channels demonstrates that knocking down cortactin decreases the actin-based immobilization of the channels. Using various deletion and mutation constructs, we show that the SH3 motif of Kv1.3 mediates the channel immobilization. Proximity ligation assays indicate that deletion or mutation of the SH3 motif also disrupts interaction of the channel with cortactin. In T-lymphocytes, the interaction between HS1 (the cortactin homologue) and Kv1.3 occurs at the immune synapse and requires the channel's C-terminal domain. These results show that actin dynamics regulates the membrane motility of Kv1.3 channels. They also provide evidence that the SH3 motif of the channel and cortactin plays key roles in this process. PMID:25739456

  16. Multistage unfolding of an SH3 domain: an initial urea-filled dry molten globule precedes a wet molten globule with non-native structure.

    Science.gov (United States)

    Dasgupta, Amrita; Udgaonkar, Jayant B; Das, Payel

    2014-06-19

    The unfolding of the SH3 domain of the PI3 kinase in aqueous urea has been studied using a synergistic experiment-simulation approach. The experimental observation of a transient wet molten globule intermediate, IU, with an unusual non-native burial of the sole Trp residue, W53, provides the benchmark for the unfolding simulations performed (eight in total, each at least 0.5 μs long). The simulations reveal that the partially unfolded IU ensemble is preceded by an early native-like molten globule intermediate ensemble I*. In the very initial stage of unfolding, dry globule conformations with the protein core filled with urea instead of water are transiently observed within the I* ensemble. Water penetration into the urea-filled core of dry globule conformations is frequently accompanied by very transient burial of W53. Later during gradual unfolding, W53 is seen to again become transiently buried in the IU ensemble for a much longer time. In the structurally heterogeneous IU ensemble, conformational flexibility of the C-terminal β-strands enables W53 burial by the formation of non-native, tertiary contacts with hydrophobic residues, which could serve to protect the protein from aggregation during unfolding.

  17. Roles for SH2 and SH3 domains in Lyn kinase association with activated FcepsilonRI in RBL mast cells revealed by patterned surface analysis.

    Science.gov (United States)

    Hammond, Stephanie; Wagenknecht-Wiesner, Alice; Veatch, Sarah L; Holowka, David; Baird, Barbara

    2009-10-01

    In mast cells, antigen-mediated cross-linking of IgE bound to its high-affinity surface receptor, FcepsilonRI, initiates a signaling cascade that culminates in degranulation and release of allergic mediators. Antigen-patterned surfaces, in which the antigen is deposited in micron-sized features on a silicon substrate, were used to examine the spatial relationship between clustered IgE-FcepsilonRI complexes and Lyn, the signal-initiating tyrosine kinase. RBL mast cells expressing wild-type Lyn-EGFP showed co-redistribution of this protein with clustered IgE receptors on antigen-patterned surfaces, whereas Lyn-EGFP containing an inhibitory point mutation in its SH2 domain did not significantly accumulate with the patterned antigen, and Lyn-EGFP with an inhibitory point mutation in its SH3 domain exhibited reduced interactions. Our results using antigen-patterned surfaces and quantitative cross-correlation image analysis reveal that both the SH2 and SH3 domains contribute to interactions between Lyn kinase and cross-linked IgE receptors in stimulated mast cells.

  18. Suppression of LIM and SH3 Domain Protein 1 (LASP1) Negatively Regulated by Androgen Receptor Delays Castration Resistant Prostate Cancer Progression.

    Science.gov (United States)

    Dejima, Takashi; Imada, Kenjiro; Takeuchi, Ario; Shiota, Masaki; Leong, Jeffrey; Tombe, Tabitha; Tam, Kevin; Fazli, Ladan; Naito, Seiji; Gleave, Martin E; Ong, Christopher J

    2017-02-01

    LIM and SH3 domain protein 1 (LASP1) has been implicated in several human malignancies and has been shown to predict PSA recurrence in prostate cancer. However, the anti-tumor effect of LASP1 knockdown and the association between LASP1 and the androgen receptor (AR) remains unclear. The aim of this study is to clarify the significance of LASP1 as a target for prostate cancer, and to test the effect of silencing LASP1 in vivo using antisense oligonucleotides (ASO). A tissue microarray (TMA) was performed to characterize the differences in LASP1 expression in prostate cancer treated after hormone deprivation therapy. Flow cytometry was used to analyze cell cycle. We designed LASP1 ASO for knockdown of LASP1 in vivo studies. The expression of LASP1 in TMA was increased after androgen ablation and persisted in castration resistant prostate cancer (CRPC). Also in TMA, compared with LNCaP cell, LASP1 expression is elevated in CRPC cell lines (C4-2 and VehA cells). Interestingly, suppression of AR elevated LASP1 expression conversely, AR activation decreased LASP1 expression. Silencing of LASP1 reduced cell growth through G1 arrest which was accompanied by a decrease of cyclin D1. Forced overexpression of LASP1 promoted cell cycle and induced cell growth which was accompanied by an increase of cyclin D1. Systemic administration of LASP1 ASO with athymic mice significantly inhibited tumor growth in CRPC xenografts. These results indicate that LASP1 is negatively regulated by AR at the transcriptional level and promotes tumor growth through induction of cell cycle, ultimately suggesting that LASP1 may be a potential target in prostate cancer treatment. Prostate 77:309-320, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  19. SH2/SH3 signaling proteins.

    Science.gov (United States)

    Schlessinger, J

    1994-02-01

    SH2 and SH3 domains are small protein modules that mediate protein-protein interactions in signal transduction pathways that are activated by protein tyrosine kinases. SH2 domains bind to short phosphotyrosine-containing sequences in growth factor receptors and other phosphoproteins. SH3 domains bind to target proteins through sequences containing proline and hydrophobic amino acids. SH2 and SH3 domain containing proteins, such as Grb2 and phospholipase C gamma, utilize these modules in order to link receptor and cytoplasmic protein tyrosine kinases to the Ras signaling pathway and to phosphatidylinositol hydrolysis, respectively. The three-dimensional structures of several SH2 and SH3 domains have been determined by NMR and X-ray crystallography, and the molecular basis of their specificity is beginning to be unveiled.

  20. Truncated ALK derived from chromosomal translocation t(2;5)(p23;q35) binds to the SH3 domain of p85-PI3K.

    Science.gov (United States)

    Polgar, Doris; Leisser, Christina; Maier, Susanne; Strasser, Stephan; Rüger, Beate; Dettke, Markus; Khorchide, Maya; Simonitsch, Ingrid; Cerni, Christa; Krupitza, Georg

    2005-02-15

    The chromosomal translocation t(2;5)(p23;q35) is associated with "Anaplastic large cell lymphomas" (ALCL), a Non Hodgkin Lymphoma occurring in childhood. The fusion of the tyrosine kinase gene-ALK (anaplastic lymphoma kinase) on chromosome 2p23 to the NPM (nucleophosmin/B23) gene on chromosome 5q35 results in a 80 kDa chimeric protein, which activates the "survival" kinase PI3K. However, the binding mechanism between truncated ALK and PI3K is poorly understood. Therefore, we attempted to elucidate the molecular interaction between ALK and the regulatory p85 subunit of PI3K. Here we provide evidence that the truncated ALK homodimer binds to the SH3 domain of p85. This finding may be useful for the development of a new target-specific intervention.

  1. The F-Actin Binding Protein Cortactin Regulates the Dynamics of the Exocytotic Fusion Pore through its SH3 Domain

    Science.gov (United States)

    González-Jamett, Arlek M.; Guerra, María J.; Olivares, María J.; Haro-Acuña, Valentina; Baéz-Matus, Ximena; Vásquez-Navarrete, Jacqueline; Momboisse, Fanny; Martinez-Quiles, Narcisa; Cárdenas, Ana M.

    2017-01-01

    Upon cell stimulation, the network of cortical actin filaments is rearranged to facilitate the neurosecretory process. This actin rearrangement includes both disruption of the preexisting actin network and de novo actin polymerization. However, the mechanism by which a Ca2+ signal elicits the formation of new actin filaments remains uncertain. Cortactin, an actin-binding protein that promotes actin polymerization in synergy with the nucleation promoting factor N-WASP, could play a key role in this mechanism. We addressed this hypothesis by analyzing de novo actin polymerization and exocytosis in bovine adrenal chromaffin cells expressing different cortactin or N-WASP domains, or cortactin mutants that fail to interact with proline-rich domain (PRD)-containing proteins, including N-WASP, or to be phosphorylated by Ca2+-dependent kinases, such as ERK1/2 and Src. Our results show that the activation of nicotinic receptors in chromaffin cells promotes cortactin translocation to the cell cortex, where it colocalizes with actin filaments. We further found that, in association with PRD-containing proteins, cortactin contributes to the Ca2+-dependent formation of F-actin, and regulates fusion pore dynamics and the number of exocytotic events induced by activation of nicotinic receptors. However, whereas the actions of cortactin on the fusion pore dynamics seems to depend on the availability of monomeric actin and its phosphorylation by ERK1/2 and Src kinases, cortactin regulates the extent of exocytosis by a mechanism independent of actin polymerization. Together our findings point out a role for cortactin as a critical modulator of actin filament formation and exocytosis in neuroendocrine cells. PMID:28522963

  2. The SH3 domain-binding T cell tyrosyl phosphoprotein p120. Demonstration of its identity with the c-cbl protooncogene product and in vivo complexes with Fyn, Grb2, and phosphatidylinositol 3-kinase

    NARCIS (Netherlands)

    Fukazawa, T.; Reedquist, K. A.; Trub, T.; Soltoff, S.; Panchamoorthy, G.; Druker, B.; Cantley, L.; Shoelson, S. E.; Band, H.

    1995-01-01

    Previously, we have identified p120 as a Fyn/Lck SH3 and SH2 domain-binding protein that is tyrosine phosphorylated rapidly after T cell receptor triggering. Here, we used direct protein purification, amino acid sequence analysis, reactivity with antibodies, and two-dimensional gel analyses to

  3. Structure of Stenotrophomonas maltophilia FeoA complexed with zinc: a unique prokaryotic SH3-domain protein that possibly acts as a bacterial ferrous iron-transport activating factor

    International Nuclear Information System (INIS)

    Su, Yi-Che; Chin, Ko-Hsin; Hung, Hui-Chih; Shen, Gwan-Han; Wang, Andrew H.-J.; Chou, Shan-Ho

    2010-01-01

    The crystal structure of FeoA from Stenotrophomonas maltophilia has been determined to a resolution of 1.7 Å using an Se single-wavelength anomalous dispersion (Se-SAD) approach and revealed a unique dimer cross-linked by two zinc ions and six chloride ions. Iron is vital to the majority of prokaryotes, with ferrous iron believed to be the preferred form for iron uptake owing to its much better solubility. The major route for bacterial ferrous iron uptake is found to be via an Feo (ferrous iron-transport) system comprising the three proteins FeoA, FeoB and FeoC. Although the structure and function of FeoB have received much attention recently, the roles played by FeoA and FeoC have been little investigated to date. Here, the tertiary structure of FeoA from Stenotrophomonas maltophilia (Sm), a vital opportunistic pathogen in immunodepressed hosts, is reported. The crystal structure of SmFeoA has been determined to a resolution of 1.7 Å using an Se single-wavelength anomalous dispersion (Se-SAD) approach. Although SmFeoA bears low sequence identity to eukaryotic proteins, its structure is found to adopt a eukaryotic SH3-domain-like fold. It also bears weak similarity to the C-terminal SH3 domain of bacterial DtxR (diphtheria toxin regulator), with some unique characteristics. Intriguingly, SmFeoA is found to adopt a unique dimer cross-linked by two zinc ions and six anions (chloride ions). Since FeoB has been found to contain a G-protein-like domain with low GTPase activity, FeoA may interact with FeoB through the SH3–G-protein domain interaction to act as a ferrous iron-transport activating factor

  4. Characterization of a novel weak interaction between MUC1 and Src-SH3 using nuclear magnetic resonance spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Gunasekara, Nirosha [Department of Laboratory Medicine and Pathology, University of Alberta, 5B4.21 WCM Health Science Centre, 8440-112th Street, Edmonton, Alberta, Canada T6G 2R7 (Canada); Sykes, Brian, E-mail: brian.sykes@ualberta.ca [Department of Biochemistry, 4-19B Medical Sciences Bldg., University of Alberta Edmonton, Alberta, Canada T6G 2H7 (Canada); Hugh, Judith, E-mail: judithh@ualberta.ca [Department of Laboratory Medicine and Pathology, University of Alberta, 5B4.21 WCM Health Science Centre, 8440-112th Street, Edmonton, Alberta, Canada T6G 2R7 (Canada)

    2012-05-18

    Highlights: Black-Right-Pointing-Pointer MUC1 binds the Src-SH3 domain potentially triggering Src dependent cell migration. Black-Right-Pointing-Pointer NMR Spectroscopy was used to monitor MUC1-CD and Src SH3 domain titrations. Black-Right-Pointing-Pointer MUC1-CD peptides bind with a low affinity (K{sub d} of 2-3 mM) to a non-canonical site. Black-Right-Pointing-Pointer Weak interactions may mediate dynamic processes like migration. Black-Right-Pointing-Pointer The MUC1-CD and Src-SH3 interaction may be a prime target to inhibit cell migration. -- Abstract: Breast cancer causes death through cancer cell migration and subsequent metastasis to distant organs. In vitro, the MUC1 mucin can mediate breast cancer cell migration by binding to intercellular adhesion molecule-1 (ICAM-1). This migration is dependent on MUC1 cytoplasmic domain (MUC1-CD) activation of the non-receptor tyrosine kinase, Src, possibly through competitive displacement of an inhibitory Src intramolecular SH3 binding. Therefore, we characterized the binding site and affinity of the MUC1-CD for Src-SH3 using multidimensional nuclear magnetic resonance (NMR) spectroscopy to monitor the titration of the {sup 15}N labeled Src-SH3 domain with synthetic native and mutant peptides of MUC1-CD. The results revealed that the dissociation constant (K{sub d}) for the interaction of the native MUC1-CD peptides and Src-SH3 domain was weak with a K{sub d} of 2-3 mM. Notably, the SH3 residues most perturbed upon peptide binding were located outside the usual hydrophobic binding cleft in a previously described alternate binding site on the Src-SH3, suggesting that MUC1-CD binds to a non-canonical site. The binding characteristics outlined here suggest that the interaction between Src-SH3 and MUC1-CD represents a novel weak electrostatic interaction of the type which is increasingly recognized as important in transient and dynamic protein complexes required for cell migration and signal transduction. As such, this

  5. Biochemical and genetic analysis of the Drk SH2/SH3 adaptor protein of Drosophila.

    Science.gov (United States)

    Raabe, T; Olivier, J P; Dickson, B; Liu, X; Gish, G D; Pawson, T; Hafen, E

    1995-06-01

    The Drk SH3-SH2-SH3 adaptor protein has been genetically identified in a screen for rate-limiting components acting downstream of the Sevenless (Sev) receptor tyrosine kinase in the developing eye of Drosophila. It provides a link between the activated Sev receptor and Sos, a guanine nucleotide release factor that activates Ras1. We have used a combined biochemical and genetic approach to study the interactions between Sev, Drk and Sos. We show that Tyr2546 in the cytoplasmic tail of Sev is required for Drk binding, probably because it provides a recognition site for the Drk SH2 domain. Interestingly, a mutation at this site does not completely block Sev function in vivo. This may suggest that Sev can signal in a Drk-independent, parallel pathway or that Drk can also bind to an intermediate docking protein. Analysis of the Drk-Sos interaction has identified a high affinity binding site for Drk SH3 domains in the Sos tail. We show that the N-terminal Drk SH3 domain is primarily responsible for binding to the tail of Sos in vitro, and for signalling to Ras in vivo.

  6. 1H and 15N NMR assignment and solution structure of the SH3 domain of spectrin: Comparison of unrefined and refined structure sets with the crystal structure

    International Nuclear Information System (INIS)

    Blanco, Francisco J.; Ortiz, Angel R.; Serrano, Luis

    1997-01-01

    The assignment of the 1 H and 15 Nnuclear magnetic resonance spectra of the Src-homology region 3 domain of chicken brain α-spectrin has been obtained. A set of solution structures has been determined from distance and dihedral angle restraints,which provide a reasonable representation of the protein structure in solution, as evaluated by a principal component analysis of the global pairwise root-mean-square deviation (rmsd) in a large set of structures consisting of the refined and unrefined solution structures and the crystal structure. The solution structure is well defined, with a lower degree of convergence between the structures in the loop regions than in the secondary structure elements. The average pairwise rmsd between the 15 refined solution structures is 0.71 ± 0.13 A for the backbone atoms and 1.43 ± 0.14 A for all heavy atoms. The solution structure is basically the same as the crystal structure. The average rmsd between the 15 refined solution structures and the crystal structure is 0.76 A for the backbone atoms and 1.45 ± 0.09 A for all heavy atoms. There are, however, small differences probably caused by intermolecular contacts in the crystal structure

  7. A unique set of SH3-SH3 interactions controls IB1 homodimerization

    DEFF Research Database (Denmark)

    Kristensen, Ole; Guenat, Sylvie; Dar, Imran

    2006-01-01

    Islet-brain 1 (IB1 or JIP-1) is a scaffold protein that interacts with components of the c-Jun N-terminal kinase (JNK) signal-transduction pathway. IB1 is expressed at high levels in neurons and in pancreatic beta-cells, where it controls expression of several insulin-secretory components...... reduces IB1-dependent basal JNK activity in 293T cells. Impaired dimerization also results in a reduction in glucose transporter type 2 expression and in glucose-dependent insulin secretion in pancreatic beta-cells. Taken together, these results indicate that IB1 homodimerization through its SH3 domain...

  8. Crystal structure of the Src family kinase Hck SH3-SH2 linker regulatory region supports an SH3-dominant activation mechanism.

    Science.gov (United States)

    Alvarado, John J; Betts, Laurie; Moroco, Jamie A; Smithgall, Thomas E; Yeh, Joanne I

    2010-11-12

    Most mammalian cell types depend on multiple Src family kinases (SFKs) to regulate diverse signaling pathways. Strict control of SFK activity is essential for normal cellular function, and loss of kinase regulation contributes to several forms of cancer and other diseases. Previous x-ray crystal structures of the SFKs c-Src and Hck revealed that intramolecular association of their Src homology (SH) 3 domains and SH2 kinase linker regions has a key role in down-regulation of kinase activity. However, the amino acid sequence of the Hck linker represents a suboptimal ligand for the isolated SH3 domain, suggesting that it may form the polyproline type II helical conformation required for SH3 docking only in the context of the intact structure. To test this hypothesis directly, we determined the crystal structure of a truncated Hck protein consisting of the SH2 and SH3 domains plus the linker. Despite the absence of the kinase domain, the structures and relative orientations of the SH2 and SH3 domains in this shorter protein were very similar to those observed in near full-length, down-regulated Hck. However, the SH2 kinase linker adopted a modified topology and failed to engage the SH3 domain. This new structure supports the idea that these noncatalytic regions work together as a "conformational switch" that modulates kinase activity in a manner unique to the SH3 domain and linker topologies present in the intact Hck protein. Our results also provide fresh structural insight into the facile induction of Hck activity by HIV-1 Nef and other Hck SH3 domain binding proteins and implicate the existence of innate conformational states unique to individual Src family members that "fine-tune" their sensitivities to activation by SH3-based ligands.

  9. Comparative Genomics and Disorder Prediction Identify Biologically Relevant SH3 Protein Interactions.

    Directory of Open Access Journals (Sweden)

    2005-08-01

    Full Text Available Protein interaction networks are an important part of the post-genomic effort to integrate a part-list view of the cell into system-level understanding. Using a set of 11 yeast genomes we show that combining comparative genomics and secondary structure information greatly increases consensus-based prediction of SH3 targets. Benchmarking of our method against positive and negative standards gave 83% accuracy with 26% coverage. The concept of an optimal divergence time for effective comparative genomics studies was analyzed, demonstrating that genomes of species that diverged very recently from Saccharomyces cerevisiae(S. mikatae, S. bayanus, and S. paradoxus, or a long time ago (Neurospora crassa and Schizosaccharomyces pombe, contain less information for accurate prediction of SH3 targets than species within the optimal divergence time proposed. We also show here that intrinsically disordered SH3 domain targets are more probable sites of interaction than equivalent sites within ordered regions. Our findings highlight several novel S. cerevisiae SH3 protein interactions, the value of selection of optimal divergence times in comparative genomics studies, and the importance of intrinsic disorder for protein interactions. Based on our results we propose novel roles for the S. cerevisiae proteins Abp1p in endocytosis and Hse1p in endosome protein sorting.

  10. Comparative genomics and disorder prediction identify biologically relevant SH3 protein interactions.

    Directory of Open Access Journals (Sweden)

    Pedro Beltrao

    2005-08-01

    Full Text Available Protein interaction networks are an important part of the post-genomic effort to integrate a part-list view of the cell into system-level understanding. Using a set of 11 yeast genomes we show that combining comparative genomics and secondary structure information greatly increases consensus-based prediction of SH3 targets. Benchmarking of our method against positive and negative standards gave 83% accuracy with 26% coverage. The concept of an optimal divergence time for effective comparative genomics studies was analyzed, demonstrating that genomes of species that diverged very recently from Saccharomyces cerevisiae(S. mikatae, S. bayanus, and S. paradoxus, or a long time ago (Neurospora crassa and Schizosaccharomyces pombe, contain less information for accurate prediction of SH3 targets than species within the optimal divergence time proposed. We also show here that intrinsically disordered SH3 domain targets are more probable sites of interaction than equivalent sites within ordered regions. Our findings highlight several novel S. cerevisiae SH3 protein interactions, the value of selection of optimal divergence times in comparative genomics studies, and the importance of intrinsic disorder for protein interactions. Based on our results we propose novel roles for the S. cerevisiae proteins Abp1p in endocytosis and Hse1p in endosome protein sorting.

  11. Arabidopsis SH3P2 is an ubiquitin-binding protein that functions together with ESCRT-I and the deubiquitylating enzyme AMSH3.

    Science.gov (United States)

    Nagel, Marie-Kristin; Kalinowska, Kamila; Vogel, Karin; Reynolds, Gregory D; Wu, Zhixiang; Anzenberger, Franziska; Ichikawa, Mie; Tsutsumi, Chie; Sato, Masa H; Kuster, Bernhard; Bednarek, Sebastian Y; Isono, Erika

    2017-08-22

    Clathrin-mediated endocytosis of plasma membrane proteins is an essential regulatory process that controls plasma membrane protein abundance and is therefore important for many signaling pathways, such as hormone signaling and biotic and abiotic stress responses. On endosomal sorting, plasma membrane proteins maybe recycled or targeted for vacuolar degradation, which is dependent on ubiquitin modification of the cargos and is driven by the endosomal sorting complexes required for transport (ESCRTs). Components of the ESCRT machinery are highly conserved among eukaryotes, but homologs of ESCRT-0 that are responsible for recognition and concentration of ubiquitylated proteins are absent in plants. Recently several ubiquitin-binding proteins have been identified that serve in place of ESCRT-0; however, their function in ubiquitin recognition and endosomal trafficking is not well understood yet. In this study, we identified Src homology-3 (SH3) domain-containing protein 2 (SH3P2) as a ubiquitin- and ESCRT-I-binding protein that functions in intracellular trafficking. SH3P2 colocalized with clathrin light chain-labeled punctate structures and interacted with clathrin heavy chain in planta , indicating a role for SH3P2 in clathrin-mediated endocytosis. Furthermore, SH3P2 cofractionates with clathrin-coated vesicles (CCVs), suggesting that it associates with CCVs in planta Mutants of SH3P2 and VPS23 genetically interact, suggesting that they could function in the same pathway. Based on these results, we suggest a role of SH3P2 as an ubiquitin-binding protein that binds and transfers ubiquitylated proteins to the ESCRT machinery.

  12. Biochemical and genetic analysis of the Drk SH2/SH3 adaptor protein of Drosophila.

    OpenAIRE

    Raabe, T; Olivier, J P; Dickson, B J; Liu, X; Gish, G D; Pawson, T; Hafen, E

    1995-01-01

    The Drk SH3-SH2-SH3 adaptor protein has been genetically identified in a screen for rate-limiting components acting downstream of the Sevenless (Sev) receptor tyrosine kinase in the developing eye of Drosophila. It provides a link between the activated Sev receptor and Sos, a guanine nucleotide release factor that activates Ras1. We have used a combined biochemical and genetic approach to study the interactions between Sev, Drk and Sos. We show that Tyr2546 in the cytoplasmic tail of Sev is r...

  13. Domain requirements for the Dock adapter protein in growth- cone signaling

    OpenAIRE

    Rao, Yong; Zipursky, S. Lawrence

    1998-01-01

    Tyrosine phosphorylation has been implicated in growth-cone guidance through genetic, biochemical, and pharmacological studies. Adapter proteins containing src homology 2 (SH2) domains and src homology 3 (SH3) domains provide a means of linking guidance signaling through phosphotyrosine to downstream effectors regulating growth-cone motility. The Drosophila adapter, Dreadlocks (Dock), the homolog of mammalian Nck containing three N-terminal SH3 domains and a single SH2 domain, is highly speci...

  14. Genetic disruption of the sh3pxd2a gene reveals an essential role in mouse development and the existence of a novel isoform of tks5.

    Science.gov (United States)

    Cejudo-Martin, Pilar; Yuen, Angela; Vlahovich, Nicole; Lock, Peter; Courtneidge, Sara A; Díaz, Begoña

    2014-01-01

    Tks5 is a scaffold protein and Src substrate involved in cell migration and matrix degradation through its essential role in invadosome formation and function. We have previously described that Tks5 is fundamental for zebrafish neural crest cell migration in vivo. In the present study, we sought to investigate the function of Tks5 in mammalian development by analyzing mice mutant for sh3pxd2a, the gene encoding Tks5. Homozygous disruption of the sh3pxd2a gene by gene-trapping in mouse resulted in neonatal death and the presence of a complete cleft of the secondary palate. Interestingly, embryonic fibroblasts from homozygous gene-trap sh3pxd2a mice lacked only the highest molecular weight band of the characteristic Tks5 triplet observed in protein extracts, leaving the lower molecular weight bands unaffected. This finding, together with the existence of two human Expressed Sequence Tags lacking the first 5 exons of SH3PXD2A, made us hypothesize about the presence of a second alternative transcription start site located in intron V. We performed 5'RACE on mouse fibroblasts and isolated a new transcript of the sh3pxd2a gene encoding a novel Tks5 isoform, that we named Tks5β. This novel isoform diverges from the long form of Tks5 in that it lacks the PX-domain, which confers affinity for phosphatidylinositol-3,4-bisphosphate. Instead, Tks5β has a short unique amino terminal sequence encoded by the newly discovered exon 6β; this exon includes a start codon located 29 bp from the 5'-end of exon 6. Tks5β mRNA is expressed in MEFs and all mouse adult tissues analyzed. Tks5β is a substrate for the Src tyrosine kinase and its expression is regulated through the proteasome degradation pathway. Together, these findings indicate the essentiality of the larger Tks5 isoform for correct mammalian development and the transcriptional complexity of the sh3pxd2a gene.

  15. Genetic disruption of the sh3pxd2a gene reveals an essential role in mouse development and the existence of a novel isoform of tks5.

    Directory of Open Access Journals (Sweden)

    Pilar Cejudo-Martin

    Full Text Available Tks5 is a scaffold protein and Src substrate involved in cell migration and matrix degradation through its essential role in invadosome formation and function. We have previously described that Tks5 is fundamental for zebrafish neural crest cell migration in vivo. In the present study, we sought to investigate the function of Tks5 in mammalian development by analyzing mice mutant for sh3pxd2a, the gene encoding Tks5. Homozygous disruption of the sh3pxd2a gene by gene-trapping in mouse resulted in neonatal death and the presence of a complete cleft of the secondary palate. Interestingly, embryonic fibroblasts from homozygous gene-trap sh3pxd2a mice lacked only the highest molecular weight band of the characteristic Tks5 triplet observed in protein extracts, leaving the lower molecular weight bands unaffected. This finding, together with the existence of two human Expressed Sequence Tags lacking the first 5 exons of SH3PXD2A, made us hypothesize about the presence of a second alternative transcription start site located in intron V. We performed 5'RACE on mouse fibroblasts and isolated a new transcript of the sh3pxd2a gene encoding a novel Tks5 isoform, that we named Tks5β. This novel isoform diverges from the long form of Tks5 in that it lacks the PX-domain, which confers affinity for phosphatidylinositol-3,4-bisphosphate. Instead, Tks5β has a short unique amino terminal sequence encoded by the newly discovered exon 6β; this exon includes a start codon located 29 bp from the 5'-end of exon 6. Tks5β mRNA is expressed in MEFs and all mouse adult tissues analyzed. Tks5β is a substrate for the Src tyrosine kinase and its expression is regulated through the proteasome degradation pathway. Together, these findings indicate the essentiality of the larger Tks5 isoform for correct mammalian development and the transcriptional complexity of the sh3pxd2a gene.

  16. Paralog-Specific Patterns of Structural Disorder and Phosphorylation in the Vertebrate SH3-SH2-Tyrosine Kinase Protein Family.

    Science.gov (United States)

    Dos Santos, Helena G; Siltberg-Liberles, Jessica

    2016-09-19

    One of the largest multigene families in Metazoa are the tyrosine kinases (TKs). These are important multifunctional proteins that have evolved as dynamic switches that perform tyrosine phosphorylation and other noncatalytic activities regulated by various allosteric mechanisms. TKs interact with each other and with other molecules, ultimately activating and inhibiting different signaling pathways. TKs are implicated in cancer and almost 30 FDA-approved TK inhibitors are available. However, specific binding is a challenge when targeting an active site that has been conserved in multiple protein paralogs for millions of years. A cassette domain (CD) containing SH3-SH2-Tyrosine Kinase domains reoccurs in vertebrate nonreceptor TKs. Although part of the CD function is shared between TKs, it also presents TK specific features. Here, the evolutionary dynamics of sequence, structure, and phosphorylation across the CD in 17 TK paralogs have been investigated in a large-scale study. We establish that TKs often have ortholog-specific structural disorder and phosphorylation patterns, while secondary structure elements, as expected, are highly conserved. Further, domain-specific differences are at play. Notably, we found the catalytic domain to fluctuate more in certain secondary structure elements than the regulatory domains. By elucidating how different properties evolve after gene duplications and which properties are specifically conserved within orthologs, the mechanistic understanding of protein evolution is enriched and regions supposedly critical for functional divergence across paralogs are highlighted. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  17. Drosophila photoreceptor axon guidance and targeting requires the dreadlocks SH2/SH3 adapter protein.

    Science.gov (United States)

    Garrity, P A; Rao, Y; Salecker, I; McGlade, J; Pawson, T; Zipursky, S L

    1996-05-31

    Mutations in the Drosophila gene dreadlocks (dock) disrupt photoreceptor cell (R cell) axon guidance and targeting. Genetic mosaic analysis and cell-type-specific expression of dock transgenes demonstrate dock is required in R cells for proper innervation. Dock protein contains one SH2 and three SH3 domains, implicating it in tyrosine kinase signaling, and is highly related to the human proto-oncogene Nck. Dock expression is detected in R cell growth cones in the target region. We propose Dock transmits signals in the growth cone in response to guidance and targeting cues. These findings provide an important step for dissection of signaling pathways regulating growth cone motility.

  18. Two-state dynamics of the SH3-SH2 tandem of Abl kinase and the allosteric role of the N-cap.

    Science.gov (United States)

    Corbi-Verge, Carles; Marinelli, Fabrizio; Zafra-Ruano, Ana; Ruiz-Sanz, Javier; Luque, Irene; Faraldo-Gómez, José D

    2013-09-03

    The regulation and localization of signaling enzymes is often mediated by accessory modular domains, which frequently function in tandems. The ability of these tandems to adopt multiple conformations is as important for proper regulation as the individual domain specificity. A paradigmatic example is Abl, a ubiquitous tyrosine kinase of significant pharmacological interest. SH3 and SH2 domains inhibit Abl by assembling onto the catalytic domain, allosterically clamping it in an inactive state. We investigate the dynamics of this SH3-SH2 tandem, using microsecond all-atom simulations and differential scanning calorimetry. Our results indicate that the Abl tandem is a two-state switch, alternating between the conformation observed in the structure of the autoinhibited enzyme and another configuration that is consistent with existing scattering data for an activated form. Intriguingly, we find that the latter is the most probable when the tandem is disengaged from the catalytic domain. Nevertheless, an amino acid stretch preceding the SH3 domain, the so-called N-cap, reshapes the free-energy landscape of the tandem and favors the interaction of this domain with the SH2-kinase linker, an intermediate step necessary for assembly of the autoinhibited complex. This allosteric effect arises from interactions between N-cap and the SH2 domain and SH3-SH2 connector, which involve a phosphorylation site. We also show that the SH3-SH2 connector plays a determinant role in the assembly equilibrium of Abl, because mutations thereof hinder the engagement of the SH2-kinase linker. These results provide a thermodynamic rationale for the involvement of N-cap and SH3-SH2 connector in Abl regulation and expand our understanding of the principles of modular domain organization.

  19. Two-state dynamics of the SH3–SH2 tandem of Abl kinase and the allosteric role of the N-cap

    Science.gov (United States)

    Corbi-Verge, Carles; Marinelli, Fabrizio; Zafra-Ruano, Ana; Ruiz-Sanz, Javier; Luque, Irene; Faraldo-Gómez, José D.

    2013-01-01

    The regulation and localization of signaling enzymes is often mediated by accessory modular domains, which frequently function in tandems. The ability of these tandems to adopt multiple conformations is as important for proper regulation as the individual domain specificity. A paradigmatic example is Abl, a ubiquitous tyrosine kinase of significant pharmacological interest. SH3 and SH2 domains inhibit Abl by assembling onto the catalytic domain, allosterically clamping it in an inactive state. We investigate the dynamics of this SH3–SH2 tandem, using microsecond all-atom simulations and differential scanning calorimetry. Our results indicate that the Abl tandem is a two-state switch, alternating between the conformation observed in the structure of the autoinhibited enzyme and another configuration that is consistent with existing scattering data for an activated form. Intriguingly, we find that the latter is the most probable when the tandem is disengaged from the catalytic domain. Nevertheless, an amino acid stretch preceding the SH3 domain, the so-called N-cap, reshapes the free-energy landscape of the tandem and favors the interaction of this domain with the SH2-kinase linker, an intermediate step necessary for assembly of the autoinhibited complex. This allosteric effect arises from interactions between N-cap and the SH2 domain and SH3–SH2 connector, which involve a phosphorylation site. We also show that the SH3–SH2 connector plays a determinant role in the assembly equilibrium of Abl, because mutations thereof hinder the engagement of the SH2-kinase linker. These results provide a thermodynamic rationale for the involvement of N-cap and SH3–SH2 connector in Abl regulation and expand our understanding of the principles of modular domain organization. PMID:23959873

  20. A Discovery Strategy for Selective Inhibitors of c-Src in Complex with the Focal Adhesion Kinase SH3/SH2-binding Region.

    Science.gov (United States)

    Moroco, Jamie A; Baumgartner, Matthew P; Rust, Heather L; Choi, Hwan Geun; Hur, Wooyoung; Gray, Nathanael S; Camacho, Carlos J; Smithgall, Thomas E

    2015-08-01

    The c-Src tyrosine kinase co-operates with the focal adhesion kinase to regulate cell adhesion and motility. Focal adhesion kinase engages the regulatory SH3 and SH2 domains of c-Src, resulting in localized kinase activation that contributes to tumor cell metastasis. Using assay conditions where c-Src kinase activity required binding to a tyrosine phosphopeptide based on the focal adhesion kinase SH3-SH2 docking sequence, we screened a kinase-biased library for selective inhibitors of the Src/focal adhesion kinase peptide complex versus c-Src alone. This approach identified an aminopyrimidinyl carbamate compound, WH-4-124-2, with nanomolar inhibitory potency and fivefold selectivity for c-Src when bound to the phospho-focal adhesion kinase peptide. Molecular docking studies indicate that WH-4-124-2 may preferentially inhibit the 'DFG-out' conformation of the kinase active site. These findings suggest that interaction of c-Src with focal adhesion kinase induces a unique kinase domain conformation amenable to selective inhibition. © 2014 John Wiley & Sons A/S.

  1. Genetic Disruption of the Sh3pxd2a Gene Reveals an Essential Role in Mouse Development and the Existence of a Novel Isoform of Tks5

    OpenAIRE

    Cejudo-Martin, Pilar; Yuen, Angela; Vlahovich, Nicole; Lock, Peter; Courtneidge, Sara A.; Díaz, Begoña

    2014-01-01

    Tks5 is a scaffold protein and Src substrate involved in cell migration and matrix degradation through its essential role in invadosome formation and function. We have previously described that Tks5 is fundamental for zebrafish neural crest cell migration in vivo. In the present study, we sought to investigate the function of Tks5 in mammalian development by analyzing mice mutant for sh3pxd2a, the gene encoding Tks5. Homozygous disruption of the sh3pxd2a gene by gene-trapping in mouse resulte...

  2. Disruption of the podosome adaptor protein TKS4 (SH3PXD2B) causes the skeletal dysplasia, eye, and cardiac abnormalities of Frank-Ter Haar Syndrome.

    Science.gov (United States)

    Iqbal, Zafar; Cejudo-Martin, Pilar; de Brouwer, Arjan; van der Zwaag, Bert; Ruiz-Lozano, Pilar; Scimia, M Cecilia; Lindsey, James D; Weinreb, Robert; Albrecht, Beate; Megarbane, Andre; Alanay, Yasemin; Ben-Neriah, Ziva; Amenduni, Mariangela; Artuso, Rosangela; Veltman, Joris A; van Beusekom, Ellen; Oudakker, Astrid; Millán, José Luis; Hennekam, Raoul; Hamel, Ben; Courtneidge, Sara A; van Bokhoven, Hans

    2010-02-12

    Frank-Ter Haar syndrome (FTHS), also known as Ter Haar syndrome, is an autosomal-recessive disorder characterized by skeletal, cardiovascular, and eye abnormalities, such as increased intraocular pressure, prominent eyes, and hypertelorism. We have conducted homozygosity mapping on patients representing 12 FTHS families. A locus on chromosome 5q35.1 was identified for which patients from nine families shared homozygosity. For one family, a homozygous deletion mapped exactly to the smallest region of overlapping homozygosity, which contains a single gene, SH3PXD2B. This gene encodes the TKS4 protein, a phox homology (PX) and Src homology 3 (SH3) domain-containing adaptor protein and Src substrate. This protein was recently shown to be involved in the formation of actin-rich membrane protrusions called podosomes or invadopodia, which coordinate pericellular proteolysis with cell migration. Mice lacking Tks4 also showed pronounced skeletal, eye, and cardiac abnormalities and phenocopied the majority of the defects associated with FTHS. These findings establish a role for TKS4 in FTHS and embryonic development. Mutation analysis revealed five different homozygous mutations in SH3PXD2B in seven FTHS families. No SH3PXD2B mutations were detected in six other FTHS families, demonstrating the genetic heterogeneity of this condition. Interestingly however, dermal fibroblasts from one of the individuals without an SH3PXD2B mutation nevertheless expressed lower levels of the TKS4 protein, suggesting a common mechanism underlying disease causation. Copyright (c) 2010 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  3. SH2/SH3 adaptor proteins can link tyrosine kinases to a Ste20-related protein kinase, HPK1.

    Science.gov (United States)

    Anafi, M; Kiefer, F; Gish, G D; Mbamalu, G; Iscove, N N; Pawson, T

    1997-10-31

    Ste20-related protein kinases have been implicated as regulating a range of cellular responses, including stress-activated protein kinase pathways and the control of cytoskeletal architecture. An important issue involves the identities of the upstream signals and regulators that might control the biological functions of mammalian Ste20-related protein kinases. HPK1 is a protein-serine/threonine kinase that possesses a Ste20-like kinase domain, and in transfected cells activates a protein kinase pathway leading to the stress-activated protein kinase SAPK/JNK. Here we have investigated candidate upstream regulators that might interact with HPK1. HPK1 possesses an N-terminal catalytic domain and an extended C-terminal tail with four proline-rich motifs. The SH3 domains of Grb2 bound in vitro to specific proline-rich motifs in the HPK1 tail and functioned synergistically to direct the stable binding of Grb2 to HPK1 in transfected Cos1 cells. Epidermal growth factor (EGF) stimulation did not affect the binding of Grb2 to HPK1 but induced recruitment of the Grb2.HPK1 complex to the autophosphorylated EGF receptor and to the Shc docking protein. Several activated receptor and cytoplasmic tyrosine kinases, including the EGF receptor, stimulated the tyrosine phosphorylation of the HPK1 serine/threonine kinase. These results suggest that HPK1, a mammalian Ste20-related protein-serine/threonine kinase, can potentially associate with protein-tyrosine kinases through interactions mediated by SH2/SH3 adaptors such as Grb2. Such interaction may provide a possible mechanism for cross-talk between distinct biochemical pathways following the activation of tyrosine kinases.

  4. Intramolecular dynamics within the N-Cap-SH3-SH2 regulatory unit of the c-Abl tyrosine kinase reveal targeting to the cellular membrane.

    Science.gov (United States)

    de Oliveira, Guilherme A P; Pereira, Elen G; Ferretti, Giulia D S; Valente, Ana Paula; Cordeiro, Yraima; Silva, Jerson L

    2013-09-27

    c-Abl is a key regulator of cell signaling and is under strict control via intramolecular interactions. In this study, we address changes in the intramolecular dynamics coupling within the c-Abl regulatory unit by presenting its N-terminal segment (N-Cap) with an alternative function in the cell as c-Abl becomes activated. Using small angle x-ray scattering, nuclear magnetic resonance, and confocal microscopy, we demonstrate that the N-Cap and the Src homology (SH) 3 domain acquire μs-ms motions upon N-Cap association with the SH2-L domain, revealing a stabilizing synergy between these segments. The N-Cap-myristoyl tether likely triggers the protein to anchor to the membrane because of these flip-flop dynamics, which occur in the μs-ms time range. This segment not only presents the myristate during c-Abl inhibition but may also trigger protein localization inside the cell in a functional and stability-dependent mechanism that is lost in Bcr-Abl(+) cells, which underlie chronic myeloid leukemia. This loss of intramolecular dynamics and binding to the cellular membrane is a potential therapeutic target.

  5. A novel mutation in the SH3BP2 gene causes cherubism: case report

    Directory of Open Access Journals (Sweden)

    Yu Shi-Feng

    2006-12-01

    Full Text Available Abstract Background Cherubism is a rare hereditary multi-cystic disease of the jaws, characterized by its typical appearance in early childhood, and stabilization and remission after puberty. It is genetically transmitted in an autosomal dominant fashion and the gene coding for SH3-binding protein 2 (SH3BP2 may be involved. Case presentation We investigated a family consisting of 21 members with 3 female affected individuals with cherubism from Northern China. Of these 21 family members, 17 were recruited for the genetic analysis. We conducted the direct sequence analysis of the SH3BP2 gene among these 17 family members. A disease-causing mutation was identified in exon 9 of the gene. It was an A1517G base change, which leads to a D419G amino acid substitution. Conclusion To our knowledge, the A1517G mutation has not been reported previously in cherubism. This finding is novel.

  6. Structural characterization of CAS SH3 domain selectivity and regulation reveals new CAS interaction partners

    Czech Academy of Sciences Publication Activity Database

    Gemperle, J.; Hexnerová, Rozálie; Lepšík, Martin; Těšina, Petr; Dibus, M.; Novotný, M.; Brábek, J.; Veverka, Václav; Rösel, D.

    2017-01-01

    Roč. 7, Aug 14 (2017), č. článku 8057. ISSN 2045-2322 R&D Projects: GA ČR(CZ) GBP208/12/G016; GA MŠk(CZ) LO1304 Institutional support: RVO:61388963 Keywords : focal adhesion kinase * Src-transformed cells * tyrosine phosphorylation Subject RIV: CE - Biochemistry OBOR OECD: Biochemistry and molecular biology Impact factor: 4.259, year: 2016 https://www.nature.com/articles/s41598-017-08303-4

  7. SH2-catalytic domain linker heterogeneity influences allosteric coupling across the SFK family.

    Science.gov (United States)

    Register, A C; Leonard, Stephen E; Maly, Dustin J

    2014-11-11

    Src-family kinases (SFKs) make up a family of nine homologous multidomain tyrosine kinases whose misregulation is responsible for human disease (cancer, diabetes, inflammation, etc.). Despite overall sequence homology and identical domain architecture, differences in SH3 and SH2 regulatory domain accessibility and ability to allosterically autoinhibit the ATP-binding site have been observed for the prototypical SFKs Src and Hck. Biochemical and structural studies indicate that the SH2-catalytic domain (SH2-CD) linker, the intramolecular binding epitope for SFK SH3 domains, is responsible for allosterically coupling SH3 domain engagement to autoinhibition of the ATP-binding site through the conformation of the αC helix. As a relatively unconserved region between SFK family members, SH2-CD linker sequence variability across the SFK family is likely a source of nonredundant cellular functions between individual SFKs via its effect on the availability of SH3 and SH2 domains for intermolecular interactions and post-translational modification. Using a combination of SFKs engineered with enhanced or weakened regulatory domain intramolecular interactions and conformation-selective inhibitors that report αC helix conformation, this study explores how SH2-CD sequence heterogeneity affects allosteric coupling across the SFK family by examining Lyn, Fyn1, and Fyn2. Analyses of Fyn1 and Fyn2, isoforms that are identical but for a 50-residue sequence spanning the SH2-CD linker, demonstrate that SH2-CD linker sequence differences can have profound effects on allosteric coupling between otherwise identical kinases. Most notably, a dampened allosteric connection between the SH3 domain and αC helix leads to greater autoinhibitory phosphorylation by Csk, illustrating the complex effects of SH2-CD linker sequence on cellular function.

  8. The role of SH3BP2 in the pathophysiology of cherubism

    Directory of Open Access Journals (Sweden)

    Reichenberger Ernst J

    2012-05-01

    Full Text Available Abstract Cherubism is a rare bone dysplasia that is characterized by symmetrical bone resorption limited to the jaws. Bone lesions are filled with soft fibrous giant cell-rich tissue that can expand and cause severe facial deformity. The disorder typically begins in children at ages of 2-5 years and the bone resorption and facial swelling continues until puberty; in most cases the lesions regress spontaneously thereafter. Most patients with cherubism have germline mutations in the gene encoding SH3BP2, an adapter protein involved in adaptive and innate immune response signaling. A mouse model carrying a Pro416Arg mutation in SH3BP2 develops osteopenia and expansile lytic lesions in bone and some soft tissue organs. In this review we discuss the genetics of cherubism, the biological functions of SH3BP2 and the analysis of the mouse model. The data suggest that the underlying cause for cherubism is a systemic autoinflammatory response to physiologic challenges despite the localized appearance of bone resorption and fibrous expansion to the jaws in humans.

  9. Interaction with the Src homology (SH3-SH2) region of the Src-family kinase Hck structures the HIV-1 Nef dimer for kinase activation and effector recruitment.

    Science.gov (United States)

    Alvarado, John Jeff; Tarafdar, Sreya; Yeh, Joanne I; Smithgall, Thomas E

    2014-10-10

    HIV-1 Nef supports high titer viral replication in vivo and is essential for AIDS progression. Nef function depends on interactions with multiple host cell effectors, including Hck and other Src-family kinases. Here we describe the x-ray crystal structure of Nef in complex with the Hck SH3-SH2 regulatory region to a resolution of 1.86 Å. The complex crystallized as a dimer of complexes, with the conserved Nef PXXPXR motif engaging the Hck SH3 domain. A new intercomplex contact was found between SH3 Glu-93, and Nef Arg-105. Mutagenesis of Hck SH3 Glu-93 interfered with Nef·Hck complex formation and kinase activation in cells. The Hck SH2 domains impinge on the N-terminal region of Nef to stabilize a dimer conformation that exposes Asp-123, a residue critical for Nef function. Our results suggest that in addition to serving as a kinase effector for Nef, Hck binding may reorganize the Nef dimer for functional interaction with other signaling partners. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Interaction with the Src Homology (SH3-SH2) Region of the Src-family Kinase Hck Structures the HIV-1 Nef Dimer for Kinase Activation and Effector Recruitment*

    Science.gov (United States)

    Alvarado, John Jeff; Tarafdar, Sreya; Yeh, Joanne I.; Smithgall, Thomas E.

    2014-01-01

    HIV-1 Nef supports high titer viral replication in vivo and is essential for AIDS progression. Nef function depends on interactions with multiple host cell effectors, including Hck and other Src-family kinases. Here we describe the x-ray crystal structure of Nef in complex with the Hck SH3-SH2 regulatory region to a resolution of 1.86 Å. The complex crystallized as a dimer of complexes, with the conserved Nef PXXPXR motif engaging the Hck SH3 domain. A new intercomplex contact was found between SH3 Glu-93, and Nef Arg-105. Mutagenesis of Hck SH3 Glu-93 interfered with Nef·Hck complex formation and kinase activation in cells. The Hck SH2 domains impinge on the N-terminal region of Nef to stabilize a dimer conformation that exposes Asp-123, a residue critical for Nef function. Our results suggest that in addition to serving as a kinase effector for Nef, Hck binding may reorganize the Nef dimer for functional interaction with other signaling partners. PMID:25122770

  11. Loss of Sh3gl2/Endophilin A1 Is a Common Event in Urothelial Carcinoma that Promotes Malignant Behavior

    Directory of Open Access Journals (Sweden)

    Shyama Majumdar

    2013-07-01

    Full Text Available Urothelial carcinoma (UC causes substantial morbidity and mortality worldwide. However, the molecular mechanisms underlying urothelial cancer development and tumor progression are still largely unknown. Using informatics analysis, we identified Sh3gl2 (endophilin A1 as a bladder urothelium-enriched transcript. The gene encoding Sh3gl2 is located on chromosome 9p, a region frequently altered in UC. Sh3gl2 is known to regulate endocytosis of receptor tyrosine kinases implicated in oncogenesis, such as the epidermal growth factor receptor (EGFR and c-Met. However, its role in UC pathogenesis is unknown. Informatics analysis of expression profiles as well as immunohistochemical staining of tissue microarrays revealed Sh3gl2 expression to be decreased in UC specimens compared to nontumor tissues. Loss of Sh3gl2 was associated with increasing tumor grade and with muscle invasion, which is a reliable predictor of metastatic disease and cancer-derived mortality. Sh3gl2 expression was undetectable in 19 of 20 human UC cell lines but preserved in the low-grade cell line RT4. Stable silencing of Sh3gl2 in RT4 cells by RNA interference 1 enhanced proliferation and colony formation in vitro, 2 inhibited EGF-induced EGFR internalization and increased EGFR activation, 3 stimulated phosphorylation of Src family kinases and STAT3, and 4 promoted growth of RT4 xenografts in subrenal capsule tissue recombination experiments. Conversely, forced re-expression of Sh3gl2 in T24 cells and silenced RT4 clones attenuated oncogenic behaviors, including growth and migration. Together, these findings identify loss of Sh3gl2 as a frequent event in UC development that promotes disease progression.

  12. Domain requirements for the Dock adapter protein in growth- cone signaling.

    Science.gov (United States)

    Rao, Y; Zipursky, S L

    1998-03-03

    Tyrosine phosphorylation has been implicated in growth-cone guidance through genetic, biochemical, and pharmacological studies. Adapter proteins containing src homology 2 (SH2) domains and src homology 3 (SH3) domains provide a means of linking guidance signaling through phosphotyrosine to downstream effectors regulating growth-cone motility. The Drosophila adapter, Dreadlocks (Dock), the homolog of mammalian Nck containing three N-terminal SH3 domains and a single SH2 domain, is highly specialized for growth-cone guidance. In this paper, we demonstrate that Dock can couple signals in either an SH2-dependent or an SH2-independent fashion in photoreceptor (R cell) growth cones, and that Dock displays different domain requirements in different neurons.

  13. Identification of two novel SH3PXD2B gene mutations in Frank-Ter Haar syndrome by exome sequencing: Case report and review of the literature.

    Science.gov (United States)

    Zrhidri, Abdelali; Jaouad, Imane Cherkaoui; Lyahyai, Jaber; Raymond, Laure; Egéa, Grégory; Taoudi, Mohamed; El Mouatassim, Said; Sefiani, Abdelaziz

    2017-09-10

    Frank-Ter Haar syndrome (FTHS) is an autosomal-recessive disorder characterized by skeletal, cardio-vascular, and eye abnormalities, such as increased intraocular pressure, prominent eyes, and hypertelorism. The most common underlying genetic defect in Frank-Ter Haar syndrome appears to be due to mutations in the SH3PXD2B gene on chromosome 5q35.1. Until now, only six mutations in SH3PXD2B gene have been identified. A genetic heterogeneity of FTHS was suggested in previous studies. FTHS was suspected clinically in a girl of 2years old, born from non-consanguineous Moroccan healthy parents. The patient had been referred to a medical genetics outpatient clinic for dysmorphic facial features. Whole Exome Sequencing (WES) was performed in the patient and her parents, in addition to Sanger sequencing that was carried out to confirm the results. We report the first description of a Moroccan FTHS patient with two novel compound heterozygous mutations c.806G>A; p.Trp269* (maternal allele) and c.892delC; p.Asp299Thrfs*44 (paternal allele) in the SH3PXD2B gene. Sanger sequencing confirmed this mutation in the affected girl and demonstrated that her parents carry this mutation in heterozygous state. Our results confirm the clinical diagnosis of FTHS in this reported family and contribute to expand the mutational spectrum of this rare disease. Our study shows also, that exome sequencing is a powerful and a cost-effective tool for the diagnosis of a supposed genetically heterogeneous disorder such FTHS. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. A micromagnetic study of domain structure modeling

    International Nuclear Information System (INIS)

    Matsuo, Tetsuji; Mimuro, Naoki; Shimasaki, Masaaki

    2008-01-01

    To develop a mesoscopic model for magnetic-domain behavior, a domain structure model (DSM) was examined and compared with a micromagnetic simulation. The domain structure of this model is given by several domains with uniform magnetization vectors and domain walls. The directions of magnetization vectors and the locations of domain walls are determined so as to minimize the magnetic total energy of the magnetic material. The DSM was modified to improve its representation capability for domain behavior. The domain wall energy is multiplied by a vanishing factor to represent the disappearance of magnetic domain. The sequential quadratic programming procedure is divided into two steps to improve an energy minimization process. A comparison with micromagnetic simulation shows that the modified DSM improves the representation accuracy of the magnetization process

  15. 15NH/D-SOLEXSY experiment for accurate measurement of amide solvent exchange rates: application to denatured drkN SH3

    International Nuclear Information System (INIS)

    Chevelkov, Veniamin; Xue, Yi; Krishna Rao, D.; Forman-Kay, Julie D.; Skrynnikov, Nikolai R.

    2010-01-01

    Amide solvent exchange rates are regarded as a valuable source of information on structure/dynamics of unfolded (disordered) proteins. Proton-based saturation transfer experiments, normally used to measure solvent exchange, are known to meet some serious difficulties. The problems mainly arise from the need to (1) manipulate water magnetization and (2) discriminate between multiple magnetization transfer pathways that occur within the proton pool. Some of these issues are specific to unfolded proteins. For example, the compensation scheme used to cancel the Overhauser effect in the popular CLEANEX experiment is not designed for use with unfolded proteins. In this report we describe an alternative experimental strategy, where amide 15 N is used as a probe of solvent exchange. The experiment is performed in 50% H 2 O-50% D 2 O solvent and is based on the (HACACO)NH pulse sequence. The resulting spectral map is fully equivalent to the conventional HSQC. To fulfill its purpose, the experiment monitors the conversion of deuterated species, 15 N D , into protonated species, 15 N H , as effected by the solvent exchange. Conceptually, this experiment is similar to EXSY which prompted the name of 15 N H/D -SOLEXSY (SOLvent EXchange SpectroscopY). Of note, our experimental scheme, which relies on nitrogen rather than proton to monitor solvent exchange, is free of the complications described above. The developed pulse sequence was used to measure solvent exchange rates in the chemically denatured state of the drkN SH3 domain. The results were found to correlate well with the CLEANEX-PM data, r = 0.97, thus providing a measure of validation for both techniques. When the experimentally measured exchange rates are converted into protection factors, most of the values fall in the range 0.5-2, consistent with random-coil behavior. However, elevated values, ca. 5, are obtained for residues R38 and A39, as well as the side-chain indole of W36. This is surprising, given that high

  16. Polarized Epithermal Neutron Studies of Magnetic Domains

    International Nuclear Information System (INIS)

    Alfimenkov, V.P.; Chernikov, A.N.; Lason, L.; Mareev, Yu. D.; Novitsky, V.V.; Pikelner, L.B.; Skoy, V.R.; Tsulaya, M.I.; Gould, C.R.; Haase, D.G.; Roberson, N.R.

    1997-01-01

    The average size and shape of magnetic domains in a material can be determined from the precession of polarized neutrons traversing the material. Epithermal neutrons (0.5eV< En<100eV), which process more slowly than thermals, effectively probe the internal structure of samples that are thick or have large domains or large internal fields. Such epithermal neutron measurements require a neutron polarizer and analyzer based on cryogenically polarized spin filters. We discuss the measurements at JINR, Dubna, of magnetic domains in a 2.0 cm. diam. crystal of holmium using 1.7 to 59eV neutrons polarized by a dynamically polarized proton target and analyzed with a statically polarized dysprosium target

  17. Polarized epithermal neutron studies of magnetic domains

    International Nuclear Information System (INIS)

    Alfimenkov, V.P.; Chernikov, A.N.; Lason, L.; Mareev, Y.D.; Novitsky, V.V.; Pikelner, L.B.; Skoy, V.R.; Tsulaya, M.I.; Gould, C.R.; Haase, D.G.; the Triangle Universities Nuclear Laboratory, Durham, North Carolina; Roberson, N.R.; the Triangle Universities Nuclear Laboratory, Durham, North Carolina

    1997-01-01

    The average size and shape of magnetic domains in a material can be determined from the precession of polarized neutrons traversing the material. Epithermal neutrons (0.5eV n <100eV), which precess more slowly than thermals, effectively probe the internal structure of samples that are thick or have large domains or large internal fields. Such epithermal neutron measurements require a neutron polarizer and analyzer based on cryogenically polarized spin filters. We discuss the measurement at JINR, Dubna, of magnetic domains in a 2.0 cm. diam. crystal of holmium using 1.7 to 59 eV neutrons polarized by a dynamically polarized proton target and analyzed with a statically polarized dysprosium target. copyright 1997 American Institute of Physics

  18. Organization of functional domains in the docking protein p130Cas

    International Nuclear Information System (INIS)

    Nasertorabi, Fariborz; Garcia-Guzman, Miguel; Briknarova, Klara; Larsen, Elise; Havert, Marnie L.; Vuori, Kristiina; Ely, Kathryn R.

    2004-01-01

    The docking protein p130Cas becomes phosphorylated upon cell adhesion to extracellular matrix proteins, and is thought to play an essential role in cell transformation. Cas transmits signals through interactions with the Src-homology 3 (SH3) and Src-homology 2 domains of FAK or v-Crk signaling molecules, or with 14-3-3 protein, as well as phosphatases PTP1B and PTP-PEST. The large (130 kDa), multi-domain Cas molecule contains an SH3 domain, a Src-binding domain, a serine-rich protein interaction region, and a C-terminal region that participates in protein interactions implicated in antiestrogen resistance in breast cancer. In this study, as part of a long-term goal to examine the protein interactions of Cas by X-ray crystallography and nuclear magnetic resonance spectroscopy, molecular constructs were designed to express two adjacent domains, the serine-rich domain and the Src-binding domain, that each participate in intermolecular contacts dependent on protein phosphorylation. The protein products are soluble, homogeneous, monodisperse, and highly suitable for structural studies to define the role of Cas in integrin-mediated cell signaling

  19. Chemical Ligation of Folded Recombinant Proteins: Segmental Isotopic Labeling of Domains for NMR Studies

    Science.gov (United States)

    Xu, Rong; Ayers, Brenda; Cowburn, David; Muir, Tom W.

    1999-01-01

    A convenient in vitro chemical ligation strategy has been developed that allows folded recombinant proteins to be joined together. This strategy permits segmental, selective isotopic labeling of the product. The src homology type 3 and 2 domains (SH3 and SH2) of Abelson protein tyrosine kinase, which constitute the regulatory apparatus of the protein, were individually prepared in reactive forms that can be ligated together under normal protein-folding conditions to form a normal peptide bond at the ligation junction. This strategy was used to prepare NMR sample quantities of the Abelson protein tyrosine kinase-SH(32) domain pair, in which only one of the domains was labeled with 15N Mass spectrometry and NMR analyses were used to confirm the structure of the ligated protein, which was also shown to have appropriate ligand-binding properties. The ability to prepare recombinant proteins with selectively labeled segments having a single-site mutation, by using a combination of expression of fusion proteins and chemical ligation in vitro, will increase the size limits for protein structural determination in solution with NMR methods. In vitro chemical ligation of expressed protein domains will also provide a combinatorial approach to the synthesis of linked protein domains.

  20. Monte Carlo studies of domain growth in two dimensions

    International Nuclear Information System (INIS)

    Yaldram, K.; Ahsan Khan, M.

    1983-07-01

    Monte Carlo simulations have been carried out to study the effect of temperature on the kinetics of domain growth. The concept of ''spatial entropy'' is introduced. It is shown that ''spatial entropy'' of the domain can be used to give a measure of the roughening of the domain. Most of the roughening is achieved during the initial time (t< or approx. 10 Monte Carlo cycles), the rate of roughening being greater for higher temperatures. For later times the roughening of the domain for different temperatures proceeds at essentially the same rate. (author)

  1. Accurate characterization of weak macromolecular interactions by titration of NMR residual dipolar couplings: application to the CD2AP SH3-C:ubiquitin complex.

    Science.gov (United States)

    Ortega-Roldan, Jose Luis; Jensen, Malene Ringkjøbing; Brutscher, Bernhard; Azuaga, Ana I; Blackledge, Martin; van Nuland, Nico A J

    2009-05-01

    The description of the interactome represents one of key challenges remaining for structural biology. Physiologically important weak interactions, with dissociation constants above 100 muM, are remarkably common, but remain beyond the reach of most of structural biology. NMR spectroscopy, and in particular, residual dipolar couplings (RDCs) provide crucial conformational constraints on intermolecular orientation in molecular complexes, but the combination of free and bound contributions to the measured RDC seriously complicates their exploitation for weakly interacting partners. We develop a robust approach for the determination of weak complexes based on: (i) differential isotopic labeling of the partner proteins facilitating RDC measurement in both partners; (ii) measurement of RDC changes upon titration into different equilibrium mixtures of partially aligned free and complex forms of the proteins; (iii) novel analytical approaches to determine the effective alignment in all equilibrium mixtures; and (iv) extraction of precise RDCs for bound forms of both partner proteins. The approach is demonstrated for the determination of the three-dimensional structure of the weakly interacting CD2AP SH3-C:Ubiquitin complex (K(d) = 132 +/- 13 muM) and is shown, using cross-validation, to be highly precise. We expect this methodology to extend the remarkable and unique ability of NMR to study weak protein-protein complexes.

  2. Clinical, in silico, and experimental evidence for pathogenicity of two novel splice site mutations in the SH3TC2 gene

    Czech Academy of Sciences Publication Activity Database

    Laššuthová, P.; Gregor, Martin; Sarnová, Lenka; Machalová, Eliška; Sedláček, Radislav; Seeman, P.

    2012-01-01

    Roč. 26, 3-4 (2012), s. 413-420 ISSN 0167-7063 R&D Projects: GA ČR GAP303/10/2044 Institutional support: RVO:68378050 Keywords : exon trapping * peripheral neuropathy * SH3TC2 gene * splice site mutation Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.159, year: 2012

  3. Domain Wall Formation in Ferromagnetic Layers: An Ab Initio Study

    Science.gov (United States)

    Herper, Heike C.

    Domain walls are an inherent feature of ferromagnetic (FM) films consisting of layers with different magnetic orientations. Since FM films are used in electrical devices the question of the influence of domain walls on, e.g., the magnetoresistance has attracted much interest. Besides discussing the resistance contribution of domain walls, it is appropriate to study different types of domain walls and their energy of formation. The behaviour of domain walls is usually discussed within model calculations. In the present paper it is done within an ab initio Green's function technique for layered systems, i.e., the fully relativistic, spin-polarized screened Korringa-Kohn Rostoker method. Results are presented for fcc Co layers covered by two semi-infinite fcc Pt(001) bulk systems or by bulk fcc Co(001), respectively. The resistance, which is caused by the different types of domain walls is discussed within a Kubo-Greenwood approach considering Co(001)/Co24/Co(001) as an example.

  4. Purification and molecular cloning of SH2- and SH3-containing inositol polyphosphate-5-phosphatase, which is involved in the signaling pathway of granulocyte-macrophage colony-stimulating factor, erythropoietin, and Bcr-Abl.

    Science.gov (United States)

    Odai, H; Sasaki, K; Iwamatsu, A; Nakamoto, T; Ueno, H; Yamagata, T; Mitani, K; Yazaki, Y; Hirai, H

    1997-04-15

    Grb2/Ash and Shc are the adapter proteins that link tyrosine-kinase receptors to Ras and make tyrosine-kinase functionally associated with receptors and Ras in fibroblasts and hematopoietic cells. Grb2/Ash and Shc have the SH3, SH2, or phosphotyrosine binding domains. These domains bind to proteins containing proline-rich regions or tyrosine-phosphorylated proteins and contribute to the association of Grb2/Ash and Shc with other signaling molecules. However, there could remain unidentified signaling molecules that physically and functionally interact with these adapter proteins and have biologically important roles in the signaling pathways. By using the GST fusion protein including the full length of Grb2/Ash, we have found that c-Cbl and an unidentified 135-kD protein (pp135) are associated with Grb2/Ash. We have also found that they become tyrosine-phosphorylated by treatment of a human leukemia cell line, UT-7, with granulocyte-macrophage colony-stimulating factor (GM-CSF). We have purified the pp135 by using GST-Grb2/Ash affinity column and have isolated the full-length complementary DNA (cDNA) encoding the pp135 using a cDNA probe, which was obtained by the degenerate polymerase chain reaction based on a peptide sequence of the purified pp135. The cloned cDNA has 3,958 nucleotides that contain a single long open reading frame of 3,567 nucleotides, encoding a 1,189 amino acid protein with a predicted molecular weight of approximately 133 kD. The deduced amino acid sequence reveals that pp135 is a protein that has one SH2, one SH3, and one proline-rich domain. The pp135, which contains two motifs conserved among the inositol polyphosphate-5-phosphatase proteins, was shown to have the inositol polyphosphate-5-phosphatase activity. The pp135 was revealed to associate constitutively with Grb2/Ash and inducibly with Shc using UT-7 cells stimulated with GM-CSF. In the cell lines derived from human chronic myelogenous leukemia, pp135 was constitutively tyrosine

  5. The conservation pattern of short linear motifs is highly correlated with the function of interacting protein domains

    Directory of Open Access Journals (Sweden)

    Wang Yiguo

    2008-10-01

    Full Text Available Abstract Background Many well-represented domains recognize primary sequences usually less than 10 amino acids in length, called Short Linear Motifs (SLiMs. Accurate prediction of SLiMs has been difficult because they are short (often Results Our combined approach revealed that SLiMs are highly conserved in proteins from functional classes that are known to interact with a specific domain, but that they are not conserved in most other protein groups. We found that SLiMs recognized by SH2 domains were highly conserved in receptor kinases/phosphatases, adaptor molecules, and tyrosine kinases/phosphatases, that SLiMs recognized by SH3 domains were highly conserved in cytoskeletal and cytoskeletal-associated proteins, that SLiMs recognized by PDZ domains were highly conserved in membrane proteins such as channels and receptors, and that SLiMs recognized by S/T kinase domains were highly conserved in adaptor molecules, S/T kinases/phosphatases, and proteins involved in transcription or cell cycle control. We studied Tyr-SLiMs recognized by SH2 domains in more detail, and found that SH2-recognized Tyr-SLiMs on the cytoplasmic side of membrane proteins are more highly conserved than those on the extra-cellular side. Also, we found that SH2-recognized Tyr-SLiMs that are associated with SH3 motifs and a tyrosine kinase phosphorylation motif are more highly conserved. Conclusion The interactome of protein domains is reflected by the evolutionary conservation of SLiMs recognized by these domains. Combining scoring matrixes derived from peptide libraries and conservation analysis, we would be able to find those protein groups that are more likely to interact with specific domains.

  6. Identification of domains of the v-crk oncogene product sufficient for association with phosphotyrosine-containing proteins.

    OpenAIRE

    Matsuda, M; Mayer, B J; Hanafusa, H

    1991-01-01

    The oncogene product of the avian sarcoma virus CT10, P47gag-crk, contains the SH2, SH2', and SH3 domains and binds proteins in a phosphotyrosine (ptyr)-dependent manner. In this study, we have determined the region of P47gag-crk essential for binding to ptyr-containing proteins. Mutant P47gag-crk proteins expressed in Escherichia coli that have the intact SH2 and SH2' regions retained the capacity to bind ptyr-containing proteins obtained from cells transformed by crk and src. The deletion o...

  7. Delusional disorder and schizophrenia: a comparative study across multiple domains.

    Science.gov (United States)

    Peralta, V; Cuesta, M J

    2016-10-01

    Delusional disorder (DD) is an under-researched condition and its relationship to schizophrenia (SZ) controversial. This study aimed to further characterize DD and to examine multi-domain evidence for the distinction between DD and SZ. Using univariate analyses we examined 146 subjects with DD, 114 subjects with paranoid SZ and 244 subjects with non-paranoid SZ on 52 characteristics from several domains including demographics, risk factors, premorbid features, illness characteristics, index episode features, delusional-related features, response to treatment and outcome. In a further step, we searched for independent associations of the examined characteristics with DD v. SZ. Univariate analyses showed that DD differed from either form of SZ in 40 characteristics, the pattern of findings indicated that paranoid SZ was much more similar to non-paranoid SZ than DD. Relative to subjects with SZ, those with DD were more likely to have drug abuse before illness onset, better premorbid sexual adjustment, later age at illness onset, higher levels of affective symptoms and lack of insight, poorer response to antipsychotic medication, better functioning in the domains of personal care, paid work and social functioning; last, subjects with DD had fewer but more severe delusions and higher ratings of conviction of delusional experience than those with SZ. Predominance of jealousy and somatic delusions was confined to subjects with DD. DD and SZ represent two distinct classes of disorders, the differential features of DD being of nosological, aetiological and therapeutic relevance.

  8. Study of domain structure in segmented polyether polyurethaneureas by PAT

    International Nuclear Information System (INIS)

    Yin Chuanyuan; Xu Weizheng; Gu Qingchao

    1990-01-01

    The domain structure of segmented polyether polyurethaneureas is investigated by means of positron annihilation technique, small angle X-ray scattering and differential scanning calorimetry. The experimental results show that the decrease of domain volume and free volume results from the increase of hard segment contents, and that the increase of domain volume and free volume results from the increase of molecular weight of soft segments

  9. Behavioural Spillover in the Environmental Domain: An Intervention Study

    DEFF Research Database (Denmark)

    Lanzini, Pietro; Thøgersen, John

    2014-01-01

    This study tests hypotheses about behavioural spillover in the environmental domain as well as the impacts of monetary inducements and verbal praise on behavioural spillover by means of a field experiment. A sample of 194 students from a large university in Denmark were randomly allocated...... to a control group or to one of two experimental conditions where they were encouraged to purchase "green" products by means of either financial compensation and incentives or verbal encouragement and praise. Participants answered a baseline survey containing questions concerning a wide range...... of environmentally relevant behaviours and after a six weeks intervention period where they were requested to keep track of their purchases by means of a shopping diary they answered a second survey with the same content as the first. This allowed us to analyse the change in self-reported pro- environmental...

  10. HCV NS5A protein containing potential ligands for both Src homology 2 and 3 domains enhances autophosphorylation of Src family kinase Fyn in B cells.

    Science.gov (United States)

    Nakashima, Kenji; Takeuchi, Kenji; Chihara, Kazuyasu; Horiguchi, Tomoko; Sun, Xuedong; Deng, Lin; Shoji, Ikuo; Hotta, Hak; Sada, Kiyonao

    2012-01-01

    Hepatitis C virus (HCV) infects B lymphocytes and induces mixed cryoglobulinemia and B cell non-Hodgkin's lymphoma. The molecular mechanism for the pathogenesis of HCV infection-mediated B cell disorders remains obscure. To identify the possible role for HCV nonstructural 5A (NS5A) protein in B cells, we generated the stable B cell lines expressing Myc-His tagged NS5A. Immunoprecipitation study in the presence or absence of pervanadate (PV) implied that NS5A was tyrosine phosphorylated by pervanadate (PV) treatment of the cells. Therefore we examined pull-down assay by using glutathione S-transferase (GST)-fusion proteins of various Src homology 2 (SH2) domains, which associates with phosphotyrosine within a specific amino acid sequence. The results showed that NS5A specifically bound to SH2 domain of Fyn from PV-treated B cells in addition to Src homology 3 (SH3) domain. Substitution of Arg(176) to Lys in the SH2 domain of Fyn abrogated this interaction. Deletion mutational analysis demonstrated that N-terminal region of NS5A was not required for the interaction with the SH2 domain of Fyn. Tyr(334) was identified as a tyrosine phosphorylation site in NS5A. Far-western analysis revealed that SH2 domain of Fyn directly bound to NS5A. Fyn and NS5A were colocalized in the lipid raft. These results suggest that NS5A directly binds to the SH2 domain of Fyn in a tyrosine phosphorylation-dependent manner. Lastly, we showed that the expression of NS5A in B cells increased phosphorylation of activation loop tyrosine in the kinase domain of Fyn. NS5A containing ligand for both SH2 and SH3 domains enhances an aberrant autophosphorylation and kinase activity of Fyn in B cells.

  11. HCV NS5A protein containing potential ligands for both Src homology 2 and 3 domains enhances autophosphorylation of Src family kinase Fyn in B cells.

    Directory of Open Access Journals (Sweden)

    Kenji Nakashima

    Full Text Available Hepatitis C virus (HCV infects B lymphocytes and induces mixed cryoglobulinemia and B cell non-Hodgkin's lymphoma. The molecular mechanism for the pathogenesis of HCV infection-mediated B cell disorders remains obscure. To identify the possible role for HCV nonstructural 5A (NS5A protein in B cells, we generated the stable B cell lines expressing Myc-His tagged NS5A. Immunoprecipitation study in the presence or absence of pervanadate (PV implied that NS5A was tyrosine phosphorylated by pervanadate (PV treatment of the cells. Therefore we examined pull-down assay by using glutathione S-transferase (GST-fusion proteins of various Src homology 2 (SH2 domains, which associates with phosphotyrosine within a specific amino acid sequence. The results showed that NS5A specifically bound to SH2 domain of Fyn from PV-treated B cells in addition to Src homology 3 (SH3 domain. Substitution of Arg(176 to Lys in the SH2 domain of Fyn abrogated this interaction. Deletion mutational analysis demonstrated that N-terminal region of NS5A was not required for the interaction with the SH2 domain of Fyn. Tyr(334 was identified as a tyrosine phosphorylation site in NS5A. Far-western analysis revealed that SH2 domain of Fyn directly bound to NS5A. Fyn and NS5A were colocalized in the lipid raft. These results suggest that NS5A directly binds to the SH2 domain of Fyn in a tyrosine phosphorylation-dependent manner. Lastly, we showed that the expression of NS5A in B cells increased phosphorylation of activation loop tyrosine in the kinase domain of Fyn. NS5A containing ligand for both SH2 and SH3 domains enhances an aberrant autophosphorylation and kinase activity of Fyn in B cells.

  12. Crystal structures of the human G3BP1 NTF2-like domain visualize FxFG Nup Repeat Specificity

    DEFF Research Database (Denmark)

    Vognsen, Tina Reinholdt; Möller, Ingvar Rúnar; Kristensen, Ole

    2013-01-01

    Ras GTPase Activating Protein SH3 Domain Binding Protein (G3BP) is a potential anti-cancer drug target implicated in several cellular functions. We have used protein crystallography to solve crystal structures of the human G3BP1 NTF2-like domain both alone and in complex with an FxFG Nup repeat...... peptide. Despite high structural similarity, the FxFG binding site is located between two alpha helices in the G3BP1 NTF2-like domain and not at the dimer interface as observed for nuclear transport factor 2. ITC studies showed specificity towards the FxFG motif but not FG and GLFG motifs. The unliganded...

  13. DC-SIGN neck domain is a pH-sensor controlling oligomerization: SAXS and hydrodynamic studies of extracellular domain.

    Science.gov (United States)

    Tabarani, Georges; Thépaut, Michel; Stroebel, David; Ebel, Christine; Vivès, Corinne; Vachette, Patrice; Durand, Dominique; Fieschi, Franck

    2009-08-07

    DC-SIGN is a C-type lectin receptor of dendritic cells and is involved in the early stages of numerous infectious diseases. DC-SIGN is organized into a tetramer enabling multivalent interaction with pathogens. Once formed, the DC-SIGN-pathogen complex can be internalized into compartments of increasing acidity. We have studied the pH dependence of the oligomerization state and conformation of the entire extracellular domain and neck region. We present evidence for equilibrium between the monomeric and tetrameric states of the extracellular domain, which exhibits a marked dependence with respect to both pH and ionic strength. Using solution x-ray scattering we have obtained a molecular envelope of the extracellular domain in which a model has been built. Our results highlight the central role of the neck domain in the pH-sensitive control of the oligomerization state, in the extended conformation of the protein, and in carbohydrate recognition domain organization and presentation. This work opens new insight into the molecular mechanism of ligand release and points to new avenues to block the first step of this important infection pathway.

  14. Domain analysis

    DEFF Research Database (Denmark)

    Hjørland, Birger

    2017-01-01

    The domain-analytic approach to knowledge organization (KO) (and to the broader field of library and information science, LIS) is outlined. The article reviews the discussions and proposals on the definition of domains, and provides an example of a domain-analytic study in the field of art studies....... Varieties of domain analysis as well as criticism and controversies are presented and discussed....

  15. Carbon-13 NMR study of switch variant anti-dansyl antibodies: Antigen binding and domain-domain interactions

    Energy Technology Data Exchange (ETDEWEB)

    Kato, Koichi; Matsunaga, Chigusa; Odaka, Asano; Yamato, Sumie; Takaha, Wakana; Shimada, Ichio; Arata, Yoji (Univ. of Tokyo (Japan))

    1991-07-02

    A {sup 13}C NMR study is reported of switch variant anti-dansyl antibodies, which possess the identical V{sub H}, V{sub L}, and C{sub L} domains in conjunction with highly homologous but not identical heavy-chain constant regions. Each of the antibodies has been selectively labeled with {sup 13}C at the carbonyl carbon of Trp, Tyr, His, or Cys residue by growing hybridoma cells in serum-free medium. Spectral assignments have been made by folowing the procedure described previously for the switch variant antibodies labeled with (1-{sup 13}C)Met. On the basis of the spectral data collected for the antibodies and their proteolytic fragments, the authors discuss how {sup 13}C NMR spectroscopy can be used for the structural analyses of antigen binding and also of domain-domain interactions in the antibody molecule.

  16. Carbon-13 NMR study of switch variant anti-dansyl antibodies: Antigen binding and domain-domain interactions

    International Nuclear Information System (INIS)

    Kato, Koichi; Matsunaga, Chigusa; Odaka, Asano; Yamato, Sumie; Takaha, Wakana; Shimada, Ichio; Arata, Yoji

    1991-01-01

    A 13 C NMR study is reported of switch variant anti-dansyl antibodies, which possess the identical V H , V L , and C L domains in conjunction with highly homologous but not identical heavy-chain constant regions. Each of the antibodies has been selectively labeled with 13 C at the carbonyl carbon of Trp, Tyr, His, or Cys residue by growing hybridoma cells in serum-free medium. Spectral assignments have been made by folowing the procedure described previously for the switch variant antibodies labeled with [1- 13 C]Met. On the basis of the spectral data collected for the antibodies and their proteolytic fragments, the authors discuss how 13 C NMR spectroscopy can be used for the structural analyses of antigen binding and also of domain-domain interactions in the antibody molecule

  17. A Biochemical/Biophysical Assay Dyad for HTS-Compatible Triaging of Inhibitors of the HIV-1 Nef/Hck SH3 Interaction

    KAUST Repository

    Breuer, Sebastian

    2013-07-26

    The current treatment regimens for HIV include over 20 anti-retrovirals. However, adverse drug effects and the emergence of drug resistance necessitates the continued improvement of the existing drug classes as well as the development of novel drugs that target as yet therapeutically unexploited viral and cellular pathways. Here we demonstrate a strategy for the discovery of protein-protein interaction inhibitors of the viral pathogenicity factor HIV-1 Nef and its interaction with the host factor SH3. A combination of a time-resolved fluorescence resonance energy resonance energy transfer-based assay and a label-free resonant waveguide grating-based assay was optimized for high-throughput screening formats.

  18. A Biochemical/Biophysical Assay Dyad for HTS-Compatible Triaging of Inhibitors of the HIV-1 Nef/Hck SH3 Interaction

    KAUST Repository

    Breuer, Sebastian; Espinola, Sheryll; Morelli, Xavier; Torbett, Bruce E; Arold, Stefan T.; Engels, Ingo H

    2013-01-01

    The current treatment regimens for HIV include over 20 anti-retrovirals. However, adverse drug effects and the emergence of drug resistance necessitates the continued improvement of the existing drug classes as well as the development of novel drugs that target as yet therapeutically unexploited viral and cellular pathways. Here we demonstrate a strategy for the discovery of protein-protein interaction inhibitors of the viral pathogenicity factor HIV-1 Nef and its interaction with the host factor SH3. A combination of a time-resolved fluorescence resonance energy resonance energy transfer-based assay and a label-free resonant waveguide grating-based assay was optimized for high-throughput screening formats.

  19. MAE measurements and studies of magnetic domains by electron microscopy

    International Nuclear Information System (INIS)

    Lo, C.C.H.

    1998-01-01

    There is a pressing need for non-destructive testing (NDT) methods for monitoring steel microstructures as they determine the mechanical properties of steel products. Magnetoacoustic emission (MAE) has potential for this application since it is sensitive to steel microstructure. The aim of this project is to study systematically the dependence of MAE upon steel microstructure, and to apply the technique to examine the industrial steel components which have complicated microstructures. Studies of MAE and Barkhausen emission (BE) were made on several systems including fully pearlitic, fully ferritic, ferritic/pearlitic and spheroidized steels. Results suggest that there is a correlation between the microstructural parameters and the MAE and BE profiles. The study of fully pearlitic steel shows that both MAE and BE are sensitive to the interlamellar spacing of pearlite. Low-carbon ferritic steel samples give different MAE and BE profiles which are dependent on ferrite grain size. Lorentz microscopy reveals that there are differences in domain structures and magnetization processes between fully ferritic and fully pearlitic samples. Study of ferritic/pearlitic samples indicates that both MAE and BE depend on the ferrite content. In the case of spheroidized steel samples MAE and BE profiles were found to be sensitive to the changes in the morphology and size of carbides. Samples of industrial steel products including pearlitic rail steel and decarburized billet were investigated. The MAE profiles obtained from the rail are consistent with those measured from the fully pearlitic rod samples. This suggests that MAE can be used for monitoring the microstructure of large steel components, provided that another technique such as BE is also used to complement the MAE measurements. In the study of the billet samples, MAE and BE were found to be dependent on the decarburization depth. The results are discussed in the context of the change in ferrite content of the surface layer

  20. Functional Independence and Interdependence of the Src Homology Domains of Phospholipase C-γ1 in B-Cell Receptor Signal Transduction

    Science.gov (United States)

    DeBell, Karen E.; Stoica, Bogdan A.; Verí, Maria-Concetta; Di Baldassarre, Angela; Miscia, Sebastiano; Graham, Laurie J.; Rellahan, Barbara L.; Ishiai, Masamichi; Kurosaki, Tomohiro; Bonvini, Ezio

    1999-01-01

    B-cell receptor (BCR)-induced activation of phospholipase C-γ1 (PLCγ1) and PLCγ2 is crucial for B-cell function. While several signaling molecules have been implicated in PLCγ activation, the mechanism coupling PLCγ to the BCR remains undefined. The role of PLCγ1 SH2 and SH3 domains at different steps of BCR-induced PLCγ1 activation was examined by reconstitution in a PLCγ-negative B-cell line. PLCγ1 membrane translocation required a functional SH2 N-terminal [SH2(N)] domain, was decreased by mutation of the SH3 domain, but was unaffected by mutation of the SH2(C) domain. Tyrosine phosphorylation did not require the SH2(C) or SH3 domains but depended exclusively on a functional SH2(N) domain, which mediated the association of PLCγ1 with the adapter protein, BLNK. Forcing PLCγ1 to the membrane via a myristoylation signal did not bypass the SH2(N) domain requirement for phosphorylation, indicating that the phosphorylation mediated by this domain is not due to membrane anchoring alone. Mutation of the SH2(N) or the SH2(C) domain abrogated BCR-stimulated phosphoinositide hydrolysis and signaling events, while mutation of the SH3 domain partially decreased signaling. PLCγ1 SH domains, therefore, have interrelated but distinct roles in BCR-induced PLCγ1 activation. PMID:10523627

  1. Finding Commonalities: Social Information Processing and Domain Theory in the Study of Aggression

    Science.gov (United States)

    Nucci, Larry

    2004-01-01

    The Arsenio and Lemerise (this issue) proposal integrating social information processing (SIP) and domain theory to study children's aggression is evaluated from a domain theory perspective. Basic tenets of domain theory rendering it compatible with SIP are discussed as well as points of divergence. Focus is directed to the proposition that…

  2. Residue-specific description of non-native transient structures in the ensemble of acid-denatured structures of the all-beta protein c-src SH3

    DEFF Research Database (Denmark)

    Rösner, Heike I; Poulsen, Flemming Martin

    2010-01-01

    -src loop to the third beta-strand, exhibited an apparent helicity of nearly 45%. Furthermore, the RT loop and the diverging turn appeared to adopt non-native-like helical conformations. Interestingly, none of the residues found in transient helical conformations exhibited significant varphi-values [Riddle......Secondary chemical shift analysis has been used to characterize the unfolded state of acid-denatured c-src SH3. Even though native c-src SH3 adopts an all-beta fold, we found evidence of transient helicity in regions corresponding to native loops. In particular, residues 40-46, connecting the n...

  3. Time-Domain Studies as a Probe of Stellar Evolution

    Science.gov (United States)

    Miller, Adam Andrew

    This dissertation focuses on the use of time-domain techniques to discover and characterize these rare astrophysical gems, while also addressing some gaps in our understanding of the earliest and latest stages of stellar evolution. The observational studies presented herein can be grouped into three parts: (i) the study of stellar death (supernovae); (ii) the study of stellar birth; and (iii) the use of modern machine-learning algorithms to discover and classify variable sources. I present observations of supernova (SN) 2006gy, the most luminous SN ever at the time of discovery, and the even-more luminous SN 2008es. Together, these two supernovae (SNe) demonstrate that core-collapse SNe can be significantly more luminous than thermonuclear type Ia SNe, and that there are multiple channels for producing these brilliant core-collapse explosions. For SN 2006gy I show that the progenitor star experienced violent, eruptive mass loss on multiple occasions during the centuries prior to explosion, a scenario that was completely unexpected within the cannon of massive-star evolution theory. I also present observations of SN 2008iy, one of the most unusual SNe ever discovered. Typical SNe take ≲3 weeks to reach peak luminosity; SN 2008iy exhibited a slow and steady rise for ˜400 days before reaching maximum brightness. The best explanation for such behavior is that the progenitor of SN 2008iy experienced an episodic phase of mass loss ˜100 yr prior to explosion. The three SNe detailed in this dissertation have altered our understanding of massive-star mass loss, namely, these SNe provide distinct evidence that post-main sequence mass loss, for at least some massive stars, occurs in sporatic fits, rather than being steady. They also demonstrate that core collapse is not restricted to the red supergiant and Wolf-Rayet stages of stellar evolution as theory predicted. Instead, some massive stars explode while in a luminous blue variable-like state. I also present

  4. Study of allosteric communications in chimeric two-domain proteins

    Czech Academy of Sciences Publication Activity Database

    Boušová, Kristýna

    2017-01-01

    Roč. 26, S1 (2017), s. 74 ISSN 0961-8368. [Annual Symposium of the Protein Society /31./. 24.07.2017-27.07.2017, Montreal] Institutional support: RVO:61388963 Keywords : protein domains * chimeric structures Subject RIV: CE - Biochemistry

  5. Purification of SOCS (Suppressor of Cytokine Signaling) SH2 Domains for Structural and Functional Studies.

    Science.gov (United States)

    Liau, Nicholas P D; Laktyushin, Artem; Babon, Jeffrey J

    2017-01-01

    Src Homology 2 (SH2) domains are protein domains which have a high binding affinity for specific amino acid sequences containing a phosphorylated tyrosine residue. The Suppressors of Cytokine Signaling (SOCS) proteins use an SH2 domain to bind to components of certain cytokine signaling pathways to downregulate the signaling cascade. The recombinantly produced SH2 domains of various SOCS proteins have been used to undertake structural and functional studies elucidating the method of how such targeting occurs. Here, we describe the protocol for the recombinant production and purification of SOCS SH2 domains, with an emphasis on SOCS3.

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

    DEFF Research Database (Denmark)

    Vognsen, Tina Reinholdt; Kristensen, Ole

    2012-01-01

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

  7. Study of domain wall propagation in nanostructured CoPt multilayers by using antisymmetric magnetoresistance

    International Nuclear Information System (INIS)

    Rodriguez-Rodriguez, G; Perez-Junquera, A; Hierro-Rodriguez, A; Montenegro, N; Alameda, J M; Velez, M; Menendez, J L; Ravelosona, D

    2010-01-01

    Domain wall propagation has been studied in perpendicular anisotropy CoPt multilayers patterned by e-beam lithography into 5 μm wide wires. Positive and negative peaks appear in time resolved magnetoresistance curves, associated to the different directions of domain wall propagation along the wires. The field dependence of domain wall velocity is well described by a creep model of a 1D wall in the presence of weak disorder with critical exponent μ=1/4.

  8. Using the Domain Identification Model to Study Major and Career Decision-Making Processes

    Science.gov (United States)

    Tendhar, Chosang; Singh, Kusum; Jones, Brett D.

    2018-01-01

    The purpose of this study was to examine the extent to which (1) a domain identification model could be used to predict students' engineering major and career intentions and (2) the MUSIC Model of Motivation components could be used to predict domain identification. The data for this study were collected from first-year engineering students. We…

  9. Collaboration Expertise in Medicine - No Evidence for Cross-Domain Application from a Memory Retrieval Study.

    Directory of Open Access Journals (Sweden)

    Jan Kiesewetter

    Full Text Available Is there evidence for expertise on collaboration and, if so, is there evidence for cross-domain application? Recall of stimuli was used to measure so-called internal collaboration scripts of novices and experts in two studies. Internal collaboration scripts refer to an individual's knowledge about how to interact with others in a social situation. METHOD—Ten collaboration experts and ten novices of the content domain social science were presented with four pictures of people involved in collaborative activities. The recall texts were coded, distinguishing between superficial and collaboration script information. RESULTS—Experts recalled significantly more collaboration script information (M = 25.20; SD = 5.88 than did novices (M = 13.80; SD = 4.47. Differences in superficial information were not found.Study 2 tested whether the differences found in Study 1 could be replicated. Furthermore, the cross-domain application of internal collaboration scripts was explored. METHOD—Twenty collaboration experts and 20 novices of the content domain medicine were presented with four pictures and four videos of their content domain and a video and picture of another content domain. All stimuli showed collaborative activities typical for the respective content domains. RESULTS—As in Study 1, experts recalled significantly more collaboration script information of their content domain (M = 71.65; SD = 33.23 than did novices (M = 54.25; SD = 15.01. For the novices, no differences were found for the superficial information nor for the retrieval of collaboration script information recalled after the other content domain stimuli.There is evidence for expertise on collaboration in memory tasks. The results show that experts hold substantially more collaboration script information than did novices. Furthermore, the differences between collaboration novices and collaboration experts occurred only in their own content domain, indicating that internal

  10. Collaboration Expertise in Medicine - No Evidence for Cross-Domain Application from a Memory Retrieval Study.

    Science.gov (United States)

    Kiesewetter, Jan; Fischer, Frank; Fischer, Martin R

    2016-01-01

    Is there evidence for expertise on collaboration and, if so, is there evidence for cross-domain application? Recall of stimuli was used to measure so-called internal collaboration scripts of novices and experts in two studies. Internal collaboration scripts refer to an individual's knowledge about how to interact with others in a social situation. METHOD— Ten collaboration experts and ten novices of the content domain social science were presented with four pictures of people involved in collaborative activities. The recall texts were coded, distinguishing between superficial and collaboration script information. RESULTS— Experts recalled significantly more collaboration script information (M = 25.20; SD = 5.88) than did novices (M = 13.80; SD = 4.47). Differences in superficial information were not found. Study 2 tested whether the differences found in Study 1 could be replicated. Furthermore, the cross-domain application of internal collaboration scripts was explored. METHOD— Twenty collaboration experts and 20 novices of the content domain medicine were presented with four pictures and four videos of their content domain and a video and picture of another content domain. All stimuli showed collaborative activities typical for the respective content domains. RESULTS— As in Study 1, experts recalled significantly more collaboration script information of their content domain (M = 71.65; SD = 33.23) than did novices (M = 54.25; SD = 15.01). For the novices, no differences were found for the superficial information nor for the retrieval of collaboration script information recalled after the other content domain stimuli. There is evidence for expertise on collaboration in memory tasks. The results show that experts hold substantially more collaboration script information than did novices. Furthermore, the differences between collaboration novices and collaboration experts occurred only in their own content domain, indicating that internal collaboration scripts

  11. Fusion protein based on Grb2-SH2 domain for cancer therapy

    International Nuclear Information System (INIS)

    Saito, Yuriko; Furukawa, Takako; Arano, Yasushi; Fujibayashi, Yasuhisa; Saga, Tsuneo

    2010-01-01

    Research highlights: → Grb2 mediates EGFR signaling through binding to phosphorylate EGFR with SH2 domain. → We generated fusion proteins containing 1 or 2 SH2 domains of Grb2 added with TAT. → The one with 2 SH2 domains (TSSF) interfered ERK phosphorylation. → TSSF significantly delayed the growth of EGFR overexpressing tumor in a mouse model. -- Abstract: Epidermal growth factor receptor (EGFR) is one of the very attractive targets for cancer therapy. In this study, we generated fusion proteins containing one or two Src-homology 2 (SH2) domains of growth factor receptor bound protein 2 (Grb2), which bind to phosphorylated EGFR, added with HIV-1 transactivating transcription for cell membrane penetration (termed TSF and TSSF, respectively). We examined if they can interfere Grb2-mediated signaling pathway and suppress tumor growth as expected from the lack of SH3 domain, which is necessary to intermediate EGFR-Grb2 cell signaling, in the fusion proteins. The transduction efficiency of TSSF was similar to that of TSF, but the binding activity of TSSF to EGFR was higher than that of TSF. Treatment of EGFR-overexpressing cells showed that TSSF decreased p42-ERK phosphorylation, while TSF did not. Both the proteins delayed cell growth but did not induce cell death in culture. TSSF also significantly suppressed tumor growth in vivo under consecutive administration. In conclusion, TSSF showed an ability to inhibit EGFR-Grb2 signaling and could have a potential to treat EGFR-activated cancer.

  12. Adaptor proteins intersectin 1 and 2 bind similar proline-rich ligands but are differentially recognized by SH2 domain-containing proteins.

    Directory of Open Access Journals (Sweden)

    Olga Novokhatska

    Full Text Available BACKGROUND: Scaffolding proteins of the intersectin (ITSN family, ITSN1 and ITSN2, are crucial for the initiation stage of clathrin-mediated endocytosis. These proteins are closely related but have implications in distinct pathologies. To determine how these proteins could be separated in certain cell pathways we performed a comparative study of ITSNs. METHODOLOGY/PRINCIPAL FINDINGS: We have shown that endogenous ITSN1 and ITSN2 colocalize and form a complex in cells. A structural comparison of five SH3 domains, which mediated most ITSNs protein-protein interactions, demonstrated a similarity of their ligand-binding sites. We showed that the SH3 domains of ITSN2 bound well-established interactors of ITSN1 as well as newly identified ITSNs protein partners. A search for a novel interacting interface revealed multiple tyrosines that could be phosphorylated in ITSN2. Phosphorylation of ITSN2 isoforms but not ITSN1 short isoform was observed in various cell lines. EGF stimulation of HeLa cells enhanced tyrosine phosphorylation of ITSN2 isoforms and enabled their recognition by the SH2 domains of the Fyn, Fgr and Abl1 kinases, the regulatory subunit of PI3K, the adaptor proteins Grb2 and Crk, and phospholipase C gamma. The SH2 domains mentioned were unable to bind ITSN1 short isoform. CONCLUSIONS/SIGNIFICANCE: Our results indicate that during evolution of vertebrates ITSN2 acquired a novel protein-interaction interface that allows its specific recognition by the SH2 domains of signaling proteins. We propose that these data could be important to understand the functional diversity of paralogous ITSN proteins.

  13. The conserved WW-domain binding sites in Dystroglycan C-terminus are essential but partially redundant for Dystroglycan function

    DEFF Research Database (Denmark)

    Yatsenko, A S; Kucherenko, M M; Pantoja, M

    2009-01-01

    BACKGROUND: Dystroglycan (Dg) is a transmembrane protein that is a part of the Dystrophin Glycoprotein Complex (DGC) which connects the extracellular matrix to the actin cytoskeleton. The C-terminal end of Dg contains a number of putative SH3, SH2 and WW domain binding sites. The most C...

  14. Windowing of THz time-domain spectroscopy signals: A study based on lactose

    Science.gov (United States)

    Vázquez-Cabo, José; Chamorro-Posada, Pedro; Fraile-Peláez, Francisco Javier; Rubiños-López, Óscar; López-Santos, José María; Martín-Ramos, Pablo

    2016-05-01

    Time-domain spectroscopy has established itself as a reference method for determining material parameters in the terahertz spectral range. This procedure requires the processing of the measured time-domain signals in order to estimate the spectral data. In this work, we present a thorough study of the properties of the signal windowing, a step previous to the parameter extraction algorithm, that permits to improve the accuracy of the results. Lactose has been used as sample material in the study.

  15. Progesterone receptor (PR) polyproline domain (PPD) mediates inhibition of epidermal growth factor receptor (EGFR) signaling in non-small cell lung cancer cells.

    Science.gov (United States)

    Kawprasertsri, Sornsawan; Pietras, Richard J; Marquez-Garban, Diana C; Boonyaratanakornkit, Viroj

    2016-05-01

    Recent evidence has suggested a possible role for progesterone receptor (PR) in the progression of non-small cell lung cancer (NSCLC). However, little is known concerning roles of PR in NSCLC. PR contains a polyproline domain (PPD), which directly binds to the SH3 domain of signaling molecules. Because PPD-SH3 interactions are essential for EGFR signaling, we hypothesized that the presence of PR-PPD interfered with EGFR-mediated signaling and cell proliferation. We examined the role of PR-PPD in cell proliferation and signaling by stably expressing PR-B, or PR-B with disrupting mutations in the PPD (PR-BΔSH3), from a tetracycline-regulated promoter in A549 NSCLC cells. PR-B dose-dependently inhibited cell growth in the absence of ligand, and progestin (R5020) treatment further suppressed the growth. Treatment with RU486 abolished PR-B- and R5020-mediated inhibition of cell proliferation. Expression of PR-BΔSH3 and treatment with R5020 or RU486 had no effect on cell proliferation. Furthermore, PR-B expression but not PR-BΔSH3 expression reduced EGF-induced A549 proliferation and activation of ERK1/2, in the absence of ligand. Taken together, our data demonstrated the significance of PR extranuclear signaling through PPD interactions in EGFR-mediated proliferation and signaling in NSCLC. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. Comparative Study of Lectin Domains in Model Species: New Insights into Evolutionary Dynamics

    Directory of Open Access Journals (Sweden)

    Sofie Van Holle

    2017-05-01

    Full Text Available Lectins are present throughout the plant kingdom and are reported to be involved in diverse biological processes. In this study, we provide a comparative analysis of the lectin families from model species in a phylogenetic framework. The analysis focuses on the different plant lectin domains identified in five representative core angiosperm genomes (Arabidopsis thaliana, Glycine max, Cucumis sativus, Oryza sativa ssp. japonica and Oryza sativa ssp. indica. The genomes were screened for genes encoding lectin domains using a combination of Basic Local Alignment Search Tool (BLAST, hidden Markov models, and InterProScan analysis. Additionally, phylogenetic relationships were investigated by constructing maximum likelihood phylogenetic trees. The results demonstrate that the majority of the lectin families are present in each of the species under study. Domain organization analysis showed that most identified proteins are multi-domain proteins, owing to the modular rearrangement of protein domains during evolution. Most of these multi-domain proteins are widespread, while others display a lineage-specific distribution. Furthermore, the phylogenetic analyses reveal that some lectin families evolved to be similar to the phylogeny of the plant species, while others share a closer evolutionary history based on the corresponding protein domain architecture. Our results yield insights into the evolutionary relationships and functional divergence of plant lectins.

  17. Using the domain identification model to study major and career decision-making processes

    Science.gov (United States)

    Tendhar, Chosang; Singh, Kusum; Jones, Brett D.

    2018-03-01

    The purpose of this study was to examine the extent to which (1) a domain identification model could be used to predict students' engineering major and career intentions and (2) the MUSIC Model of Motivation components could be used to predict domain identification. The data for this study were collected from first-year engineering students. We used a structural equation model to test the hypothesised relationship between variables in the partial domain identification model. The findings suggested that engineering identification significantly predicted engineering major intentions and career intentions and had the highest effect on those two variables compared to other motivational constructs. Furthermore, results suggested that success, interest, and caring are plausible contributors to students' engineering identification. Overall, there is strong evidence that the domain identification model can be used as a lens to study career decision-making processes in engineering, and potentially, in other fields as well.

  18. Crystallization and preliminary crystallographic studies of the W2 domain of Drosophila melanogaster eukaryotic translation initiation factor 5C domain-containing protein

    International Nuclear Information System (INIS)

    Zhao, Hui; Wang, Hong; Liu, Huihui; Teng, Maikun; Li, Xu

    2012-01-01

    The crystallization and preliminary crystallographic studies of the carboxy-terminal domain of D. melanogaster eukaryotic translation initiation factor 5C domain-containing protein are reported. The Drosophila melanogaster eukaryotic translation initiation factor 5C domain-containing protein (ECP) is composed of two independently folded domains which belong to the basic leucine-zipper and W2 domain-containing protein (BZW) family. Based on the sequence similarity between the C-terminal W2 domain of ECP and some eukaryotic translation initiation factors (such as eIF2B∊, eIF4γ, eIF5 etc.), ECP has been speculated to participate in the translation initiation process. Structural information on the C-terminal W2 domain of ECP would be helpful in understanding the specific cellular function of this protein. Here, the W2 domain of ECP was expressed and crystallized. Crystals grown by the hanging-drop vapour-diffusion method diffracted to 2.70 Å resolution and belonged to space group I4, with unit-cell parameters a = b = 81.05, c = 57.44 Å. The Matthews coefficient suggested that there was one molecule per asymmetric unit in the crystal

  19. Transferência de fatores genéticos de resistência a Hemileia vastatrix para o cultivar mundo novo Transference of the genes SH2 and SH3 for resistance to Hemileia vastatrix to the mundo novo cultivar of C. arabica

    Directory of Open Access Journals (Sweden)

    A. Carvalho

    1977-01-01

    Full Text Available Cafeeiros portadores dos fatores genéticos SH2 ou SH2 e SH3, simultaneamente, que conferem resistência a várias raças de Hemileia vastatrix, foram cruzados com plantas selecionadas do cultivar mundo novo de Coffea arabica a fim de se obter, em F2, recombinações com resistência a esse patógeno e elevada produtividade. Analisaram-se 14 populações F2 segregando apenas para o fator SH2, oito para os fatores SH2 e HS3, e três populações que dão, em sua descendência, plantas do grupo A, resistentes a todas as raças do patógeno até agora conhecidas. De 22.356 cafeeiros originalmente plantados em ensaio, a duas mudas por cova, em parcelas casualizadas, fez-se uma primeira seleção deixando apenas um cafeeiro por cova, reduzindo-se para 11.178 as plantas em estudo. Com base no aspecto vegetativo, na produtividade, na ausência de defeitos nos frutos e na reação de resistência ao agente causal da ferrugem, realizaram-se sucessivas seleções escolhendo-se finalmente, apenas 100 cafeeiros do tipo mundo novo e resistentes a H. vastatrix para derivação das populações F2 e prosseguimento da seleção.Coffee trees homozygous for the alleles SH2 or SH2 and SH3 which confer resistance to several physiological races of Hemileia vastatrix, were crossed to selected plants of Mundo Novo cultivar of Coffea arabica and the F2 generations were studied aiming to develop new high yielding and resistant coffee recombinations. A complete randomized field trial was stablished including 14 F2 populations segregating for SH2, eight populations segregating for SH2 and SH3 genes, and three populations segregating for plants of the A group of reaction to the H. vastatrix attack. A total of 22,356 F2 plants were analysed. Based on the plant vigor, yield capacity, percentage of normal developed seeds and resistance reaction to H. vastatrix, three successive series of selection were undertaken leaving only 100 coffee trees for development of F3 populations

  20. Avaliação e seleção de progênies F3 de cafeeiros de porte baixo com o gene SH3 de resistência a Hemileia vastatrix Berk. et Br. Evaluation and selection of Coffea arabica F3 progenies with low height and the leaf-rust SH3 resistence gene

    Directory of Open Access Journals (Sweden)

    Albano Silva da Conceição

    2005-01-01

    Full Text Available Com o objetivo de avaliar e selecionar progênies F3 de cafeeiros de porte baixo com o gene SH3 de resistência à ferrugem, foram estudadas 36 progênies de cafeeiros tipo arábica (Coffea arabica L. , em geração F3, resultantes dos cruzamentos dirigidos entre as cultivares Catuaí Vermelho IAC 46 e Catuaí Vermelho IAC 81 com o acesso IAC 1110 (BA-10. Esse último, originário da Índia, é fonte dos genes SH2SH3 que conferem resistência a Hemileia vastatrix. O experimento, estabelecido em 1988 no Centro Experimental do Instituto Agronômico, em Campinas (SP, no delineamento experimental em blocos ao acaso com seis repetições, duas plantas por parcela e no espaçamento 3,0 x 1,8 m, utilizou como testemunha a cultivar Catuaí Vermelho IAC 81, totalizando 37 tratamentos. Avaliaram-se no campo, a produção de café (média de sete colheitas, vigor vegetativo, resistência à ferrugem, porte da planta, coloração das folhas novas e maturação dos frutos. Os frutos das plantas mais produtivas foram analisados em laboratório quanto ao rendimento, tipos de sementes, peneira média e massa de 1000 grãos. A análise da variância dos dados de produção das progênies evidenciou que houve diferenças significativas entre as progênies, ao nível de 1% de probabilidade, pelo teste F. Foram selecionadas 11 progênies com média superior à testemunha e dentro dessas, 39 cafeeiros. Das 25 progênies restantes foram selecionados mais 15 cafeeiros produtivos e resistentes ao agente da ferrugem. Desses 54 cafeeiros, foram selecionados os 18 que apresentaram peneira média acima de 15,5 e maior freqüência de grãos normais do tipo chato. As progênies dessas plantas selecionadas foram avaliadas na geração F4, em fase de mudas, quando se verificou que dez delas estavam em homozigoze para porte baixo. Com as 18 plantas, o Programa de Melhoramento do Café, no IAC, terá continuidade como progênies F4, visando à obtenção de nova cultivar de

  1. Nanoscopic studies of domain structure dynamics in ferroelectric La:HfO2 capacitors

    Science.gov (United States)

    Buragohain, P.; Richter, C.; Schenk, T.; Lu, H.; Mikolajick, T.; Schroeder, U.; Gruverman, A.

    2018-05-01

    Visualization of domain structure evolution under an electrical bias has been carried out in ferroelectric La:HfO2 capacitors by a combination of Piezoresponse Force Microscopy (PFM) and pulse switching techniques to study the nanoscopic mechanism of polarization reversal and the wake-up process. It has been directly shown that the main mechanism behind the transformation of the polarization hysteretic behavior and an increase in the remanent polarization value upon the alternating current cycling is electrically induced domain de-pinning. PFM imaging and local spectroscopy revealed asymmetric switching in the La:HfO2 capacitors due to a significant imprint likely caused by the different boundary conditions at the top and bottom interfaces. Domain switching kinetics can be well-described by the nucleation limited switching model characterized by a broad distribution of the local switching times. It has been found that the domain velocity varies significantly throughout the switching process indicating strong interaction with structural defects.

  2. Impact of corpus domain for sentiment classification: An evaluation study using supervised machine learning techniques

    Science.gov (United States)

    Karsi, Redouane; Zaim, Mounia; El Alami, Jamila

    2017-07-01

    Thanks to the development of the internet, a large community now has the possibility to communicate and express its opinions and preferences through multiple media such as blogs, forums, social networks and e-commerce sites. Today, it becomes clearer that opinions published on the web are a very valuable source for decision-making, so a rapidly growing field of research called “sentiment analysis” is born to address the problem of automatically determining the polarity (Positive, negative, neutral,…) of textual opinions. People expressing themselves in a particular domain often use specific domain language expressions, thus, building a classifier, which performs well in different domains is a challenging problem. The purpose of this paper is to evaluate the impact of domain for sentiment classification when using machine learning techniques. In our study three popular machine learning techniques: Support Vector Machines (SVM), Naive Bayes and K nearest neighbors(KNN) were applied on datasets collected from different domains. Experimental results show that Support Vector Machines outperforms other classifiers in all domains, since it achieved at least 74.75% accuracy with a standard deviation of 4,08.

  3. Simultaneous storage of medical images in the spatial and frequency domain: A comparative study

    Directory of Open Access Journals (Sweden)

    Acharya U Rajendra

    2004-06-01

    Full Text Available Abstract Background Digital watermarking is a technique of hiding specific identification data for copyright authentication. This technique is adapted here for interleaving patient information with medical images, to reduce storage and transmission overheads. Methods The patient information is encrypted before interleaving with images to ensure greater security. The bio-signals are compressed and subsequently interleaved with the image. This interleaving is carried out in the spatial domain and Frequency domain. The performance of interleaving in the spatial, Discrete Fourier Transform (DFT, Discrete Cosine Transform (DCT and Discrete Wavelet Transform (DWT coefficients is studied. Differential pulse code modulation (DPCM is employed for data compression as well as encryption and results are tabulated for a specific example. Results It can be seen from results, the process does not affect the picture quality. This is attributed to the fact that the change in LSB of a pixel changes its brightness by 1 part in 256. Spatial and DFT domain interleaving gave very less %NRMSE as compared to DCT and DWT domain. Conclusion The Results show that spatial domain the interleaving, the %NRMSE was less than 0.25% for 8-bit encoded pixel intensity. Among the frequency domain interleaving methods, DFT was found to be very efficient.

  4. On the study of the magnetic domain pattern via the initial magnetization curve

    International Nuclear Information System (INIS)

    Wu, T.

    1997-01-01

    This study inquires into the relationships between the initial magnetization curve and the magnetic domain pattern in the demagnetized states for amorphous TbFeCo as well as multilayered Co/Pd thin film samples. This was done specifically through an investigation of different demagnetized states of samples demagnetized by a variety of methods. The magnetic domain pattern for the sample demagnetized by an in-plane magnetic field and for the sample demagnetized by a perpendicular magnetic field was found to be quite different even though both states have zero magnetization. The former state has denser and finer domains than the latter. In addition, both states were studied in light of the initial magnetization curves obtained by measurements of the magneto-optic Kerr effect and the extraordinary Hall effect. Moreover, the initial magnetization for the fine domains increases with an increase in magnetic field, while for the coarse domains, the initial magnetization remains at zero for magnetic field below coercivity H c , then rises sharply to saturated magnetization when magnetic field is nearly equal to H c . copyright 1997 American Institute of Physics

  5. Domain-growth kinetics and aspects of pinning: A Monte Carlo simulation study

    DEFF Research Database (Denmark)

    Castán, T.; Lindgård, Per-Anker

    1991-01-01

    By means of Monte Carlo computer simulations we study the domain-growth kinetics after a quench across a first-order line to very low and moderate temperatures in a multidegenerate system with nonconserved order parameter. The model is a continuous spin model relevant for martensitic transformati......By means of Monte Carlo computer simulations we study the domain-growth kinetics after a quench across a first-order line to very low and moderate temperatures in a multidegenerate system with nonconserved order parameter. The model is a continuous spin model relevant for martensitic...... to cross over from n = 1/4 at T approximately 0 to n = 1/2 with temperature for models with pinnings of types (a) and (b). For topological pinnings at T approximately 0, n is consistent with n = 1/8, a value conceivable for several levels of hierarchically interrelated domain-wall movement. When...

  6. Contribution of the LIM domain and nebulin-repeats to the interaction of Lasp-2 with actin filaments and focal adhesions.

    Directory of Open Access Journals (Sweden)

    Hiroyuki Nakagawa

    Full Text Available Lasp-2 binds to actin filaments and concentrates in the actin bundles of filopodia and lamellipodia in neural cells and focal adhesions in fibroblastic cells. Lasp-2 has three structural regions: a LIM domain, a nebulin-repeat region, and an SH3 domain; however, the region(s responsible for its interactions with actin filaments and focal adhesions are still unclear. In this study, we revealed that the N-terminal fragment from the LIM domain to the first nebulin-repeat module (LIM-n1 retained actin-binding activity and showed a similar subcellular localization to full-length lasp-2 in neural cells. The LIM domain fragment did not interact with actin filaments or localize to actin filament bundles. In contrast, LIM-n1 showed a clear subcellular localization to filopodial actin bundles. Although truncation of the LIM domain caused the loss of F-actin binding activity and the accumulation of filopodial actin bundles, these truncated fragments localized to focal adhesions. These results suggest that lasp-2 interactions with actin filaments are mediated through the cooperation of the LIM domain and the first nebulin-repeat module in vitro and in vivo. Actin filament binding activity may be a major contributor to the subcellular localization of lasp-2 to filopodia but is not crucial for lasp-2 recruitment to focal adhesions.

  7. A study on group decision-making based fault multi-symptom-domain consensus diagnosis

    International Nuclear Information System (INIS)

    He Yongyong; Chu Fulei; Zhong Binglin

    2001-01-01

    In the field of fault diagnosis for rotating machines, the conventional methods or the neural network based methods are mainly single symptom domain based methods, and the diagnosis accuracy of which is not always satisfactory. In this paper, in order to utilize multiple symptom domains to improve the diagnosis accuracy, an idea of fault multi-symptom-domain consensus diagnosis is developed. From the point of view of the group decision-making, two particular multi-symptom-domain diagnosis strategies are proposed. The proposed strategies use BP (Back-Propagation) neural networks as diagnosis models in various symptom domains, and then combine the outputs of these networks by two combination schemes, which are based on Dempster-Shafer evidence theory and fuzzy integral theory, respectively. Finally, a case study pertaining to the fault diagnosis for rotor-bearing systems is given in detail, and the results show that the proposed diagnosis strategies are feasible and more efficient than conventional stacked-vector methods

  8. The study of co-citation analysis and knowledge structure on healthcare domain

    Science.gov (United States)

    Chu, Kuo-Chung; Liu, Wen-I.; Tsai, Ming-Yu

    2012-11-01

    With the prevalence of Internet and digital archives, the online e-journal database facilitates scholars to search literature in a research domain, or to cross-search an inter-disciplined field; the key literature can be efficiently traced out. This study intends to build a Web-based citation analysis system, which consists of four modules, they are: 1) literature search module; (2) statistics module; (3) articles analysis module; and (4) co-citation analysis module. The system focuses on PubMed Central dataset that has 170,000 records. In a research domain, a specific keyword searches in terms of authors, journals, and core issues. In addition, we use data mining techniques for co-citation analysis. The results assist researchers with in-depth understanding of the domain knowledge. Having an automated system for co-citation analysis, it helps to understand changes, trends, and knowledge structure of research domain. For the best of our knowledge, the proposed system differentiates from existing online electronic retrieval database analysis function. Perhaps, the proposed system is going to be a value-added database of healthcare domain, and hope to contribute the researchers.

  9. Subcritical switching dynamics and humidity effects in nanoscale studies of domain growth in ferroelectric thin films

    International Nuclear Information System (INIS)

    Blaser, Cédric; Paruch, Patrycja

    2015-01-01

    Ferroelectric domain switching in c-axis-oriented epitaxial Pb(Zr 0.2 Ti 0.8 )O 3 thin films was studied using biased scanning probe microscopy tips. While linear and logarithmic dependence of domain size on tip bias and writing time, respectively, are well known, we report an additional linear dependence on relative humidity in the 28–65% range. We map out the switched domain size as a function of both the tip bias and the applied pulse time and describe a growth-limited regime for very short pulses and a nucleation-limited regime for very low tip bias. Using ‘interrupted-switching’ measurements, we probe the nucleation regime with subcritical pulses and identify a surprisingly long relaxation time on the order of 100 ms, which we relate to ionic redistribution both on the surface and within the thin film itself. (paper)

  10. Chiral Domain Structure in Superfluid 3He-A Studied by Magnetic Resonance Imaging

    Science.gov (United States)

    Kasai, J.; Okamoto, Y.; Nishioka, K.; Takagi, T.; Sasaki, Y.

    2018-05-01

    The existence of a spatially varying texture in superfluid 3He is a direct manifestation of the complex macroscopic wave function. The real space shape of the texture, namely, a macroscopic wave function, has been studied extensively with the help of theoretical modeling but has never been directly observed experimentally with spatial resolution. We have succeeded in visualizing the texture by a specialized magnetic resonance imaging. With this new technology, we have discovered that the macroscopic chiral domains, of which sizes are as large as 1 mm, and corresponding chiral domain walls exist rather stably in 3He - A film at temperatures far below the transition temperature.

  11. Synthetic protein scaffolds based on peptide motifs and cognate adaptor domains for improving metabolic productivity

    Directory of Open Access Journals (Sweden)

    Anselm H.C. Horn

    2015-11-01

    Full Text Available The efficiency of many cellular processes relies on the defined interaction among different proteins within the same metabolic or signaling pathway. Consequently, a spatial colocalization of functionally interacting proteins has frequently emerged during evolution. This concept has been adapted within the synthetic biology community for the purpose of creating artificial scaffolds. A recent advancement of this concept is the use of peptide motifs and their cognate adaptor domains. SH2, SH3, GBD, and PDZ domains have been used most often in research studies to date. The approach has been successfully applied to the synthesis of a variety of target molecules including catechin, D-glucaric acid, H2, hydrochinone, resveratrol, butyrate, gamma-aminobutyric acid, and mevalonate. Increased production levels of up to 77-fold have been observed compared to non-scaffolded systems. A recent extension of this concept is the creation of a covalent linkage between peptide motifs and adaptor domains, which leads to a more stable association of the scaffolded systems and thus bears the potential to further enhance metabolic productivity.

  12. Guanylate kinase domains of the MAGUK family scaffold proteins as specific phospho-protein-binding modules.

    Science.gov (United States)

    Zhu, Jinwei; Shang, Yuan; Xia, Caihao; Wang, Wenning; Wen, Wenyu; Zhang, Mingjie

    2011-11-25

    Membrane-associated guanylate kinases (MAGUKs) are a large family of scaffold proteins that play essential roles in tissue developments, cell-cell communications, cell polarity control, and cellular signal transductions. Despite extensive studies over the past two decades, the functions of the signature guanylate kinase domain (GK) of MAGUKs are poorly understood. Here we show that the GK domain of DLG1/SAP97 binds to asymmetric cell division regulatory protein LGN in a phosphorylation-dependent manner. The structure of the DLG1 SH3-GK tandem in complex with a phospho-LGN peptide reveals that the GMP-binding site of GK has evolved into a specific pSer/pThr-binding pocket. Residues both N- and C-terminal to the pSer are also critical for the specific binding of the phospho-LGN peptide to GK. We further demonstrate that the previously reported GK domain-mediated interactions of DLGs with other targets, such as GKAP/DLGAP1/SAPAP1 and SPAR, are also phosphorylation dependent. Finally, we provide evidence that other MAGUK GKs also function as phospho-peptide-binding modules. The discovery of the phosphorylation-dependent MAGUK GK/target interactions indicates that MAGUK scaffold-mediated signalling complex organizations are dynamically regulated.

  13. Influence of social relationship domains and their combinations on incident dementia: a prospective cohort study.

    Science.gov (United States)

    Saito, Tami; Murata, Chiyoe; Saito, Masashige; Takeda, Tokunori; Kondo, Katsunori

    2018-01-01

    Social relationships consist of mutually related but distinct dimensions. It remains unclear how these domains independently contribute to incident dementia. This large-scale, prospective cohort study examines associations between the social relationship domains as well as their combinations and incident dementia among community-dwelling older adults. We analysed data from 13 984 community-dwelling adults aged 65+ without long-term care needs living in Aichi prefecture in Japan. Incident dementia was assessed based on the Long-term Care Insurance records, followed for 3436 days from the baseline survey conducted in 2003. Three social relationships domains (social support, social networks and social activities) were further divided into a total of eight subdomains. A social relationship diversity score was calculated using the social relationship domains which were significantly related to incident dementia. A Cox proportional hazards model showed that being married, exchanging support with family members, having contact with friends, participating in community groups and engaging in paid work were related to a lower likelihood of developing incident dementia, controlling for covariates and other social relationship domains. The diversity scores, ranging from 0 to 5, were linearly associated with incident dementia (psocial relationship subdomains which were negatively related to incident dementia, suggesting that dementia may potentially be prevented by enhancing these social relationships. Future studies should examine independent pathways between each social relationship domain and incident dementia. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  14. Integrating Moral and Social Development within Middle School Social Studies: A Social Cognitive Domain Approach

    Science.gov (United States)

    Nucci, Larry; Creane, Michael W.; Powers, Deborah W.

    2015-01-01

    Eleven teachers and 254 urban middle-school students comprised the sample of this study examining the social and moral development outcomes of the integration of social cognitive domain theory within regular classroom instruction. Participating teachers were trained to construct and implement history lessons that stimulated students' moral…

  15. A guideline to study the feasibility domain of multi-trophic and changing ecological communities.

    Science.gov (United States)

    Song, Chuliang; Rohr, Rudolf P; Saavedra, Serguei

    2018-04-24

    The feasibility domain of an ecological community can be described by the set of environmental abiotic and biotic conditions under which all co-occurring and interacting species in a given site and time can have positive abundances. Mathematically, the feasibility domain corresponds to the parameter space compatible with positive (feasible) solutions at equilibrium for all the state variables in a system under a given model of population dynamics. Under specific dynamics, the existence of a feasible equilibrium is a necessary condition for species persistence regardless of whether the feasible equilibrium is dynamically stable or not. Thus, the size of the feasibility domain can also be used as an indicator of the tolerance of a community to random environmental variations. This has motivated a rich research agenda to estimate the feasibility domain of ecological communities. However, these methodologies typically assume that species interactions are static, or that input and output energy flows on each trophic level are unconstrained. Yet, this is different to how communities behave in nature. Here, we present a step-by-step quantitative guideline providing illustrative examples, computational code, and mathematical proofs to study systematically the feasibility domain of ecological communities under changes of interspecific interactions and subject to different constraints on the trophic energy flows. This guideline covers multi-trophic communities that can be formed by any type of interspecific interactions. Importantly, we show that the relative size of the feasibility domain can significantly change as a function of the biological information taken into consideration. We believe that the availability of these methods can allow us to increase our understanding about the limits at which ecological communities may no longer tolerate further environmental perturbations, and can facilitate a stronger integration of theoretical and empirical research. Copyright

  16. Opioid Prescribing After Curative-Intent Surgery: A Qualitative Study Using the Theoretical Domains Framework.

    Science.gov (United States)

    Lee, Jay S; Parashar, Vartika; Miller, Jacquelyn B; Bremmer, Samantha M; Vu, Joceline V; Waljee, Jennifer F; Dossett, Lesly A

    2018-07-01

    Excessive opioid prescribing is common after curative-intent surgery, but little is known about what factors influence prescribing behaviors among surgeons. To identify targets for intervention, we performed a qualitative study of opioid prescribing after curative-intent surgery using the Theoretical Domains Framework, a well-established implementation science method for identifying factors influencing healthcare provider behavior. Prior to data collection, we constructed a semi-structured interview guide to explore decision making for opioid prescribing. We then conducted interviews with surgical oncology providers at a single comprehensive cancer center. Interviews were recorded, transcribed verbatim, then independently coded by two investigators using the Theoretical Domains Framework to identify theoretical domains relevant to opioid prescribing. Relevant domains were then linked to behavior models to select targeted interventions likely to improve opioid prescribing. Twenty-one subjects were interviewed from November 2016 to May 2017, including attending surgeons, resident surgeons, physician assistants, and nurses. Five theoretical domains emerged as relevant to opioid prescribing: environmental context and resources; social influences; beliefs about consequences; social/professional role and identity; and goals. Using these domains, three interventions were identified as likely to change opioid prescribing behavior: (1) enablement (deploy nurses during preoperative visits to counsel patients on opioid use); (2) environmental restructuring (provide on-screen prompts with normative data on the quantity of opioid prescribed); and (3) education (provide prescribing guidelines). Key determinants of opioid prescribing behavior after curative-intent surgery include environmental and social factors. Interventions targeting these factors are likely to improve opioid prescribing in surgical oncology.

  17. Domains and domain loss

    DEFF Research Database (Denmark)

    Haberland, Hartmut

    2005-01-01

    politicians and in the media, especially in the discussion whether some languages undergo ‘domain loss’ vis-à-vis powerful international languages like English. An objection that has been raised here is that domains, as originally conceived, are parameters of language choice and not properties of languages...

  18. X ray topographic study of defects and magnetic domains in rare earth iron garnets

    International Nuclear Information System (INIS)

    Mathiot, Alain.

    1975-11-01

    X ray topographs allow simultaneous observations of crystalline defects and magnetic domain walls (except 180 deg ones). The easy magnetization directions of rare earth iron garnets are and the equilibrium texture of (110) silices is limited by a rectangular array of 71 deg and 109 deg walls. Since the anisotropy and magnetostriction of the choosen compounds (TbIG and DyIG) increase sharply when the temperature is lowered, the influence of these parameters has been studied between 300K and 4.2K. Because of the increase of spontaneous magnetization and anisotropy, the domain number increases at low temperatures and the texture becomes less sensitive to the crystal imperfections. Besides the 109 deg walls disappear almost completely from the pattern; this has been shown to be due to the respective values of the wall energies, and particularly to the influence of the K 2 anisotropy constant. The contrasts observed on the topographs increase also sharply, because of the high values of the lambda 111 coefficient of spontaneous magnetostriction at low temperatures. A splitting of the Brugg reflection peak into two, below 60K for TbIG, each part corresponding to one family of domains, allowed a direct of lambda 111 . The garnets are materials chosen to study domain walls because of the large range of the anisotropy and magnetostriction values obtained in those compounds [fr

  19. Impact of spectral nudging and domain size in studies of RCM response to parameter modification

    Energy Technology Data Exchange (ETDEWEB)

    Separovic, Leo; Laprise, Rene [Universite du Quebec a Montreal, Centre pour l' Etude et la Simulation du Climat a l' Echelle Regionale (ESCER), Montreal, QC (Canada); Universite du Quebec a Montreal (UQAM), Montreal, QC (Canada); Elia, Ramon de [Universite du Quebec a Montreal, Centre pour l' Etude et la Simulation du Climat a l' Echelle Regionale (ESCER), Montreal, QC (Canada); Consortium Ouranos, Montreal, QC (Canada)

    2012-04-15

    The paper aims at finding an RCM configuration that facilitates studies devoted to quantifying RCM response to parameter modification. When using short integration times, the response of the time-averaged variables to RCM modification tend to be blurred by the noise originating in the lack of predictability of the instantaneous atmospheric states. Two ways of enhancing the signal-to-noise ratio are studied in this work: spectral nudging and reduction of the computational domain size. The approach followed consists in the analysis of the sensitivity of RCM-simulated seasonal averages to perturbations of two parameters controlling deep convection and stratiform condensation, perturbed one at a time. Sensitivity is analyzed within different simulation configurations obtained by varying domain size and using the spectral nudging option. For each combination of these factors multiple members of identical simulations that differ exclusively in initial conditions are also generated to provide robust estimates of the sensitivities (the signal) and sample the noise. Results show that the noise magnitude is decreased both by reduction of domain size and the spectral nudging. However, the reduction of domain size alters some sensitivity signals. When spectral nudging is used significant alterations of the signal are not found. (orig.)

  20. TEM studies of domain formation mechanisms in MnV{sub 2}O{sub 4}

    Energy Technology Data Exchange (ETDEWEB)

    Murakami, Y., E-mail: murakami@tagen.tohoku.ac.jp [Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, Sendai 980-8577 (Japan); Advanced Science Institute, RIKEN, Wako 351-0198 (Japan); Nii, Y.; Arima, T. [Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, Sendai 980-8577 (Japan); Shindo, D. [Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, Sendai 980-8577 (Japan); Advanced Science Institute, RIKEN, Wako 351-0198 (Japan); Yanagisawa, K. [Advanced Science Institute, RIKEN, Wako 351-0198 (Japan); Okinawa Institute of Science and Technology, Onna-son, Okinawa 904-0412 (Japan); Tonomura, A. [Advanced Science Institute, RIKEN, Wako 351-0198 (Japan); Central Research Laboratory, Hitachi Ltd., Hatoyama 350-0395 (Japan); Okinawa Institute of Science and Technology, Onna-son, Okinawa 904-0412 (Japan)

    2013-11-15

    Highlights: ► Irregular shape of the phase boundary, due to the small transformation strain. ► TEM studies demonstrate the essential reduction of net magnetization by cooling. ► Twining morphology provides a key to understating of the anomalous magnetic domains. -- Abstract: Crystallographic and magnetic domains produced in a spinel-type compound MnV{sub 2}O{sub 4}, which exhibits a type of giant magnetostriction attributed to twin boundary motion, have been studied using transmission electron microscopy techniques. Although MnV{sub 2}O{sub 4} undergoes a displacive cubic-to-tetragonal transformation upon cooling, it does not show a well-defined habit plane (i.e. the plane with a specific index that is favored for minimizing the transformation) due to the small elongation/contraction in the lattice. Electron holography demonstrates a considerable reduction in the magnetic signal by cooling the tetragonal phase to 40 K. Despite the elimination of micrometer-scale ferrimagnetic domains, weak magnetic contrast still remained, indicating small residual magnetic domains in particular portions, such as in the crosshatch of twinning pairs.

  1. Examining the Use of a Visual Analytics System for Sensemaking Tasks: Case Studies with Domain Experts.

    Science.gov (United States)

    Kang, Youn-Ah; Stasko, J

    2012-12-01

    While the formal evaluation of systems in visual analytics is still relatively uncommon, particularly rare are case studies of prolonged system use by domain analysts working with their own data. Conducting case studies can be challenging, but it can be a particularly effective way to examine whether visual analytics systems are truly helping expert users to accomplish their goals. We studied the use of a visual analytics system for sensemaking tasks on documents by six analysts from a variety of domains. We describe their application of the system along with the benefits, issues, and problems that we uncovered. Findings from the studies identify features that visual analytics systems should emphasize as well as missing capabilities that should be addressed. These findings inform design implications for future systems.

  2. In vivo binding properties of SH2 domains from GTPase-activating protein and phosphatidylinositol 3-kinase.

    Science.gov (United States)

    Cooper, J A; Kashishian, A

    1993-01-01

    We have used a transient expression system and mutant platelet-derived growth factor (PDGF) receptors to study the binding specificities of the Src homology 2 (SH2) regions of the Ras GTPase-activator protein (GAP) and the p85 alpha subunit of phosphatidylinositol 3-kinase (PI3 kinase). A number of fusion proteins, each tagged with an epitope allowing recognition by a monoclonal antibody, were expressed at levels comparable to those of endogenous GAP. Fusion proteins containing the central SH2-SH3-SH2 region of GAP or the C-terminal region of p85 alpha, which includes two SH2 domains, bound to PDGF receptors in response to PDGF stimulation. Both fusion proteins showed the same requirements for tyrosine phosphorylation sites in the PDGF receptor as the full-length proteins from which they were derived, i.e., binding of the GAP fusion protein was reduced by mutation of Tyr-771, and binding of the p85 fusion protein was reduced by mutation of Tyr-740, Tyr-751, or both residues. Fusion proteins containing single SH2 domains from either GAP or p85 alpha did not bind detectably to PDGF receptors in this system, suggesting that two SH2 domains in a single polypeptide cooperate to raise the affinity of binding. The sequence specificities of individual SH2 domains were deduced from the binding properties of fusion proteins containing one SH2 domain from GAP and another from p85. The results suggest that the C-terminal GAP SH2 domain specifies binding to Tyr-771, the C-terminal p85 alpha SH2 domain binds to either Tyr-740 or Tyr-751, and each protein's N-terminal SH2 domain binds to unidentified phosphorylation sites.(ABSTRACT TRUNCATED AT 250 WORDS) Images PMID:8382774

  3. Study of domain depinning during repeated polarization reversal in hard PZT ceramics using acoustic emission

    International Nuclear Information System (INIS)

    Prabakar, K; Rao, S P Mallikarjun

    2006-01-01

    Acoustic emission (AE) has been studied during repeated polarization reversals (at 50 Hz) in hard PZT-8 ceramics. The AE and hysteresis loop were monitored at regular intervals of electric field (±20 kV cm -1 peak) application till 10 8 cycles. The sample did not fatigue and an increase in saturation polarization (Ps) was observed. AE was observed with zero threshold till 10 5 cycles when the field was increasing in both half cycles of the applied field. The initial increase in AE activity with increasing number of field cycles till 10 5 was explained on the basis of defect dipoles encouraging the 90 deg. domain switches, i.e. domain depinning. The decrease in AE activity, an increase in threshold field for the observed AE and a further increase in Ps after 10 5 cycles were explained based on the changes in the orientation of defect dipoles with respect to Ps due to the applied field cycles. This was found to encourage the 180 0 domain switches but pin the 90 deg. domains. An increase in AE at 10 8 cycles after applying a higher field of ±25 kV cm -1 was found to be mainly due to microcracking

  4. Distal loop flexibility of a regulatory domain modulates dynamics and activity of C-terminal SRC kinase (csk.

    Directory of Open Access Journals (Sweden)

    Sulyman Barkho

    Full Text Available The Src family of tyrosine kinases (SFKs regulate numerous aspects of cell growth and differentiation and are under the principal control of the C-terminal Src Kinase (Csk. Csk and SFKs share a modular design with the kinase domain downstream of the N-terminal SH2 and SH3 domains that regulate catalytic function and membrane localization. While the function of interfacial segments in these multidomain kinases are well-investigated, little is known about how surface sites and long-range, allosteric coupling control protein dynamics and catalytic function. The SH2 domain of Csk is an essential component for the down-regulation of all SFKs. A unique feature of the SH2 domain of Csk is the tight turn in place of the canonical CD loop in a surface site far removed from kinase domain interactions. In this study, we used a combination of experimental and computational methods to probe the importance of this difference by constructing a Csk variant with a longer SH2 CD loop to mimic the flexibility found in homologous kinase SH2 domains. Our results indicate that while the fold and function of the isolated domain and the full-length kinase are not affected by loop elongation, native protein dynamics that are essential for efficient catalysis are perturbed. We also identify key motifs and routes through which the distal SH2 site might influence catalysis at the active site. This study underscores the sensitivity of intramolecular signaling and catalysis to native protein dynamics that arise from modest changes in allosteric regions while providing a potential strategy to alter intrinsic activity and signaling modulation.

  5. In-situ TEM study of domain switching in GaN thin films

    Science.gov (United States)

    Wang, Baoming; Wang, Tun; Haque, Aman; Snure, Michael; Heller, Eric; Glavin, Nicholas

    2017-09-01

    Microstructural response of gallium nitride (GaN) films, grown by metal-organic chemical vapor deposition, was studied as a function of applied electrical field. In-situ transmission electron microscopy showed sudden change in the electron diffraction pattern reflecting domain switching at around 20 V bias, applied perpendicular to the polarization direction. No such switching was observed for thicker films or for the field applied along the polarization direction. This anomalous behavior is explained by the nanoscale size effects on the piezoelectric coefficients of GaN, which can be 2-3 times larger than the bulk value. As a result, a large amount of internal energy can be imparted in 100 nm thick films to induce domain switching at relatively lower voltages to induce such events at the bulk scale.

  6. Slow coarsening of B2-ordered domains at low temperatures: A kinetic Monte Carlo study

    International Nuclear Information System (INIS)

    Le Floc'h, D.; Bellon, P.; Athenes, M.

    2000-01-01

    The kinetics of the ordering and coarsening of B2-ordered domains is studied using atomistic kinetic Monte Carlo simulations. Special emphasis is put on the effect of annealing temperature, alloy composition, and atom dynamics on the coarsening behavior. When atomic diffusion proceeds by vacancy jumps to nearest-neighbor sites, a transient slow coarsening regime is observed at temperatures below half the order-disorder transition temperature T c . It results in apparent coarsening exponents that decrease with decreasing the annealing temperature. Values as low as 0.14 are measured at 0.25T c . Slow transients take place in both stoichiometric and nonstoichiometric alloys. These regimes are correlated with the transient creation of excess antisites during domain disappearance. Since antiphase boundary mobility decreases with increasing antisite concentration, this transient excess results in the slow coarsening observed in simulations. (c) 2000 The American Physical Society

  7. A micromagnetic study of the oscillations of pinned domain walls in magnetic ribbons

    Energy Technology Data Exchange (ETDEWEB)

    Alejos, Oscar [Dpto. Electricidad y Electronica, Universidad de Valladolid, 47071 Valladolid (Spain)]. E-mail: oscaral@ee.uva.es; Torres, Carlos [Dpto. Electricidad y Electronica, Universidad de Valladolid, 47071 Valladolid (Spain); Hernandez-Gomez, Pablo [Dpto. Electricidad y Electronica, Universidad de Valladolid, 47071 Valladolid (Spain); Lopez-Diaz, Luis [Dpto. Fisica Aplicada, Universidad de Salamanca, 37071 Salamanca (Spain); Torres, Luis [Dpto. Fisica Aplicada, Universidad de Salamanca, 37071 Salamanca (Spain); Martinez, Eduardo [Dpto. Ingenieria Electromecanica, Universidad de Burgos, 09001 Burgos (Spain)

    2007-09-15

    The work studies the dynamics of domain walls in magnetic ribbons with thicknesses of the order of magnitude of the permalloy exchange length (5.7 nm) by means of micromagnetic simulations. Two small defects are symmetrically placed on both edges of the ribbon, one on each edge, occupying the whole ribbon thickness. One transverse domain wall is pinned by the defects, in a head-to-head configuration. A free wall oscillation is forced by applying a static external magnetic field in the direction of the large axis until the wall reaches a new equilibrium position (elongation), and then removed. Three dynamic regimes are observed depending on the size of the cross ribbon section.

  8. A micromagnetic study of the oscillations of pinned domain walls in magnetic ribbons

    International Nuclear Information System (INIS)

    Alejos, Oscar; Torres, Carlos; Hernandez-Gomez, Pablo; Lopez-Diaz, Luis; Torres, Luis; Martinez, Eduardo

    2007-01-01

    The work studies the dynamics of domain walls in magnetic ribbons with thicknesses of the order of magnitude of the permalloy exchange length (5.7 nm) by means of micromagnetic simulations. Two small defects are symmetrically placed on both edges of the ribbon, one on each edge, occupying the whole ribbon thickness. One transverse domain wall is pinned by the defects, in a head-to-head configuration. A free wall oscillation is forced by applying a static external magnetic field in the direction of the large axis until the wall reaches a new equilibrium position (elongation), and then removed. Three dynamic regimes are observed depending on the size of the cross ribbon section

  9. Inversion domain boundaries in GaN studied by X-ray microprobe

    Energy Technology Data Exchange (ETDEWEB)

    Martinez-Criado, Gema; Tucoulou, Remi; Cloetens, Peter; Sans, Juan Angel; Susini, Jean [European Synchrotron Radiation Facility, Experiments Division, Grenoble (France); Somogyi, Andrea [Experiments Division, Synchrotron SOLEIL, Gif-sur-Yvette (France); Alen, Benito [Microelectronics Institute Madrid, CNM-CSIC, Madrid (Spain); Miskys, Claudio [Walter Schottky Institute, Technical University Munich, Garching (Germany)

    2010-02-15

    In this study, we report on the application of synchrotron spectro-microscopic techniques to the examination of inversion domain boundaries formed intentionally in a GaN-based lateral polarity heterostructure. Using X-ray sub-microbeams, no evidence of field-driven electrodiffusion effects has been observed on spatially separated inversion domain boundaries. In addition, XANES data around the Ga K-edge strongly supported hexagonal Ga site configurations, suggesting high local order reconstruction. Based on inner-shell excited luminescence on the micrometer scale, the uniform spectral distribution of the radiative centers was discussed. (copyright 2010 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  10. Insulin-induced tyrosine phosphorylation of a M(r) 70,000 protein revealed by association with the Src homology 2 (SH2) and SH3 domains of p120GAP and Grb2

    NARCIS (Netherlands)

    Medema, J. P.; Pronk, G. J.; de Vries-Smits, A. M.; Clark, R.; McCormick, F.; Bos, J. L.

    1996-01-01

    We have used two approaches to identify possible substrates of the insulin receptor (IR) tyrosine kinase. First, we used a potent tyrosine phosphatase inhibitor, phenylarsine oxide (PAO), which is reported to be specific for the insulin-induced signal transduction route, to augment tyrosine

  11. Descriptive epidemiology of domain-specific sitting in working adults: the Stormont Study.

    Science.gov (United States)

    Clemes, Stacy A; Houdmont, Jonathan; Munir, Fehmidah; Wilson, Kelly; Kerr, Robert; Addley, Ken

    2016-03-01

    Given links between sedentary behaviour and unfavourable health outcomes, there is a need to understand the influence of socio-demographic factors on sedentary behaviour to inform effective interventions. This study examined domain-specific sitting times reported across socio-demographic groups of office workers. The analyses are cross-sectional and based on a survey conducted within the Stormont Study, which is tracking employees in the Northern Ireland Civil Service. Participants self-reported their daily sitting times across multiple domains (work, TV, travel, PC use and leisure) on workdays and non-workdays, along with their physical activity and socio-demographic variables (sex, age, marital status, BMI, educational attainment and work pattern). Total and domain-specific sitting on workdays and non-workdays were compared across socio-demographic groups using multivariate analyses of covariance. Completed responses were obtained from 4436 participants. For the whole sample, total daily sitting times were higher on workdays in comparison to non-workdays (625 ± 168 versus 469 ± 210 min/day, P leisure-time sitting. © The Author 2015. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  12. Dimerization of the docking/adaptor protein HEF1 via a carboxy-terminal helix-loop-helix domain.

    Science.gov (United States)

    Law, S F; Zhang, Y Z; Fashena, S J; Toby, G; Estojak, J; Golemis, E A

    1999-10-10

    HEF1, p130(Cas), and Efs define a family of multidomain docking proteins which plays a central coordinating role for tyrosine-kinase-based signaling related to cell adhesion. HEF1 function has been specifically implicated in signaling pathways important for cell adhesion and differentiation in lymphoid and epithelial cells. While the SH3 domains and SH2-binding site domains (substrate domains) of HEF1 family proteins are well characterized and binding partners known, to date the highly conserved carboxy-terminal domains of the three proteins have lacked functional definition. In this study, we have determined that the carboxy-terminal domain of HEF1 contains a divergent helix-loop-helix (HLH) motif. This motif mediates HEF1 homodimerization and HEF1 heterodimerization with a recognition specificity similar to that of the transcriptional regulatory HLH proteins Id2, E12, and E47. We had previously demonstrated that the HEF1 carboxy-terminus expressed as a separate domain in yeast reprograms cell division patterns, inducing constitutive pseudohyphal growth. Here we show that pseudohyphal induction by HEF1 requires an intact HLH, further supporting the idea that this motif has an effector activity for HEF1, and implying that HEF1 pseudohyphal activity derives in part from interactions with yeast helix-loop-helix proteins. These combined results provide initial insight into the mode of function of the HEF1 carboxy-terminal domain and suggest that the HEF1 protein may interact with cellular proteins which control differentiation. Copyright 1999 Academic Press.

  13. Not all risks are created equal: A twin study and meta-analyses of risk taking across seven domains.

    Science.gov (United States)

    Wang, X T Xiao-Tian; Zheng, Rui; Xuan, Yan-Hua; Chen, Jie; Li, Shu

    2016-11-01

    Humans routinely deal with both traditional and novel risks. Different kinds of risks have been a driving force for both evolutionary adaptations and personal development. This study explored the genetic and environmental influences on human risk taking in different task domains. Our approach was threefold. First, we integrated several scales of domain-specific risk-taking propensity and developed a synthetic scale, including both evolutionarily typical and modern risks in the following 7 domains: cooperation/competition, safety, reproduction, natural/physical risk, moral risk, financial risk, and gambling. Second, we conducted a twin study using the scale to estimate the contributions of genes and environment to risk taking in each of these 7 domains. Third, we conducted a series of meta-analyses of extant twin studies across the 7 risk domains. The results showed that individual differences in risk-taking propensity and its consistency across domains were mainly regulated by additive genetic influences and individually unique environmental experiences. The heritability estimates from the meta-analyses ranged from 29% in financial risk taking to 55% in safety. Supporting the notion of risk-domain specificity, both the behavioral and genetic correlations among the 7 domains were generally low. Among the relatively few correlations between pairs of risk domains, our analysis revealed a common genetic factor that regulates moral, financial, and natural/physical risk taking. This is the first effort to separate genetic and environmental influences on risk taking across multiple domains in a single study and integrate the findings of extant twin studies via a series of meta-analyses conducted in different task domains. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  14. Computational Study of Correlated Domain Motions in the AcrB Efflux Transporter

    Directory of Open Access Journals (Sweden)

    Robert Schulz

    2015-01-01

    Full Text Available As active part of the major efflux system in E. coli bacteria, AcrB is responsible for the uptake and pumping of toxic substrates from the periplasm toward the extracellular space. In combination with the channel protein TolC and membrane fusion protein AcrA, this efflux pump is able to help the bacterium to survive different kinds of noxious compounds. With the present study we intend to enhance the understanding of the interactions between the domains and monomers, for example, the transduction of mechanical energy from the transmembrane domain into the porter domain, correlated motions of different subdomains within monomers, and cooperative effects between monomers. To this end, targeted molecular dynamics simulations have been employed either steering the whole protein complex or specific parts thereof. By forcing only parts of the complex towards specific conformational states, the risk for transient artificial conformations during the simulations is reduced. Distinct cooperative effects between the monomers in AcrB have been observed. Possible allosteric couplings have been identified providing microscopic insights that might be exploited to design more efficient inhibitors of efflux systems.

  15. An Application Domain Extension to CityGML for immovable property taxation: A Turkish case study

    Science.gov (United States)

    Çağdaş, Volkan

    2013-04-01

    It is generally acknowledged that immovable property taxes are one of the main revenue sources for local government. The literature emphasizes that the administration of property taxes needs well-developed inventories or registers that provide complete and accurate records of the taxed properties and their legal-economic attributes. This requirement is generally fulfilled by Spatial Data Infrastructures (SDIs) in which the coordinate exchange and sharing of geo-spatial data is provided by separate registers/information systems such as: cadastral systems, building and address registers. Recently, the Open Geospatial Consortium presented a core component of a 3D SDI in the form of an international domain standard for representing, storing and exchanging 3D city models. The CityGML allows the semantic and 3D geometrical representation of physical objects but does not deal with the legal and administrative aspects of the city objects which are required for the process of property taxation. This paper outlines the development of an Application Domain Extension (ADE) for the immovable property taxation domain that expands the CityGML data model with the legal and administrative concepts defined in Turkish Law. The study shows that this ADE could be a 3D national data model for municipal information systems and facilitate a more efficient taxation process, as well as providing data for urban planning, facility management and other municipal services.

  16. Numerical Capacities as Domain-Specific Predictors beyond Early Mathematics Learning: A Longitudinal Study

    Science.gov (United States)

    Reigosa-Crespo, Vivian; González-Alemañy, Eduardo; León, Teresa; Torres, Rosario; Mosquera, Raysil; Valdés-Sosa, Mitchell

    2013-01-01

    The first aim of the present study was to investigate whether numerical effects (Numerical Distance Effect, Counting Effect and Subitizing Effect) are domain-specific predictors of mathematics development at the end of elementary school by exploring whether they explain additional variance of later mathematics fluency after controlling for the effects of general cognitive skills, focused on nonnumerical aspects. The second aim was to address the same issues but applied to achievement in mathematics curriculum that requires solutions to fluency in calculation. These analyses assess whether the relationship found for fluency are generalized to mathematics content beyond fluency in calculation. As a third aim, the domain specificity of the numerical effects was examined by analyzing whether they contribute to the development of reading skills, such as decoding fluency and reading comprehension, after controlling for general cognitive skills and phonological processing. Basic numerical capacities were evaluated in children of 3rd and 4th grades (n=49). Mathematics and reading achievements were assessed in these children one year later. Results showed that the size of the Subitizing Effect was a significant domain-specific predictor of fluency in calculation and also in curricular mathematics achievement, but not in reading skills, assessed at the end of elementary school. Furthermore, the size of the Counting Effect also predicted fluency in calculation, although this association only approached significance. These findings contrast with proposals that the core numerical competencies measured by enumeration will bear little relationship to mathematics achievement. We conclude that basic numerical capacities constitute domain-specific predictors and that they are not exclusively “start-up” tools for the acquisition of Mathematics; but they continue modulating this learning at the end of elementary school. PMID:24255710

  17. Structural studies of the activation of the two component receiver domain NTRC by multidimensional heteronuclear NMR

    Energy Technology Data Exchange (ETDEWEB)

    Nohaile, Michael James [Univ. of California, Berkeley, CA (United States). Dept. of Chemistry

    1996-05-01

    Multidimensional heteronuclear NMR spectroscopy was used to investigate the N-terminal domain of the transcriptional enhancer NTRC (NiTrogen Regulatory protein C). This domain belongs to the family of receiver domains of two-component regulatory systems involved in signal transduction. Phosphorylation of NTRC at D54 leads to an activated form of the molecule which stimulates transcription of genes involved in nitrogen regulation. Three and four dimensional NMR techniques were used to determine an intermediate resolution structure of the unphosphorylated, inactive form of the N-terminal domain of NTRC. The structure is comprised of five α-helices and a five-stranded β-sheet in a (β/α)5 topology. Analysis of the backbone dynamics of NTRC indicate that helix 4 and strand 5 are significantly more flexible than the rest of the secondary structure of the protein and that the loops making up the active site are flexible. The short lifetime of phospho-NTRC hampers the study of this form. However, conditions for determining the resonance assignments and, possibly, the three dimensional structure of phosphorylated NTRC have been obtained. Tentative assignments of the phosphorylated form indicate that the majority of the changes that NTRC experiences upon phosphorylation occur in helix 3, strand 4, helix 4, strand 5, and the loop between strand 5 and helix 5 (the 3445 face of NTRC) as well as near the site of phosphorylation. In order to examine a stable, activated form of the protein, constitutively active mutants of NTRC were investigated.

  18. Numerical capacities as domain-specific predictors beyond early mathematics learning: a longitudinal study.

    Science.gov (United States)

    Reigosa-Crespo, Vivian; González-Alemañy, Eduardo; León, Teresa; Torres, Rosario; Mosquera, Raysil; Valdés-Sosa, Mitchell

    2013-01-01

    The first aim of the present study was to investigate whether numerical effects (Numerical Distance Effect, Counting Effect and Subitizing Effect) are domain-specific predictors of mathematics development at the end of elementary school by exploring whether they explain additional variance of later mathematics fluency after controlling for the effects of general cognitive skills, focused on nonnumerical aspects. The second aim was to address the same issues but applied to achievement in mathematics curriculum that requires solutions to fluency in calculation. These analyses assess whether the relationship found for fluency are generalized to mathematics content beyond fluency in calculation. As a third aim, the domain specificity of the numerical effects was examined by analyzing whether they contribute to the development of reading skills, such as decoding fluency and reading comprehension, after controlling for general cognitive skills and phonological processing. Basic numerical capacities were evaluated in children of 3(rd) and 4(th) grades (n=49). Mathematics and reading achievements were assessed in these children one year later. Results showed that the size of the Subitizing Effect was a significant domain-specific predictor of fluency in calculation and also in curricular mathematics achievement, but not in reading skills, assessed at the end of elementary school. Furthermore, the size of the Counting Effect also predicted fluency in calculation, although this association only approached significance. These findings contrast with proposals that the core numerical competencies measured by enumeration will bear little relationship to mathematics achievement. We conclude that basic numerical capacities constitute domain-specific predictors and that they are not exclusively "start-up" tools for the acquisition of Mathematics; but they continue modulating this learning at the end of elementary school.

  19. Absence of phase-dependent noise in time-domain reflectivity studies of impulsively excited phonons

    KAUST Repository

    Hussain, A.

    2010-06-17

    There have been several reports of phase-dependent noise in time-domain reflectivity studies of optical phonons excited by femtosecond laser pulses in semiconductors, semimetals, and superconductors. It was suggested that such behavior is associated with the creation of squeezed phonon states although there is no theoretical model that directly supports such a proposal. We have experimentally re-examined the studies of phonons in bismuth and gallium arsenide, and find no evidence of any phase-dependent noise signature associated with the phonons. We place an upper limit on any such noise at least 40–50 dB lower than previously reported.

  20. Absence of phase-dependent noise in time-domain reflectivity studies of impulsively excited phonons

    KAUST Repository

    Hussain, A.; Andrews, S. R.

    2010-01-01

    There have been several reports of phase-dependent noise in time-domain reflectivity studies of optical phonons excited by femtosecond laser pulses in semiconductors, semimetals, and superconductors. It was suggested that such behavior is associated with the creation of squeezed phonon states although there is no theoretical model that directly supports such a proposal. We have experimentally re-examined the studies of phonons in bismuth and gallium arsenide, and find no evidence of any phase-dependent noise signature associated with the phonons. We place an upper limit on any such noise at least 40–50 dB lower than previously reported.

  1. Thermodynamic study of the native and phosphorylated regulatory domain of the CFTR

    Energy Technology Data Exchange (ETDEWEB)

    Marasini, Carlotta, E-mail: marasini@ge.ibf.cnr.it [Istituto di Biofisica, Consiglio Nazionale delle Ricerche, Via De Marini 6, 16149 Genova (Italy); Galeno, Lauretta; Moran, Oscar [Istituto di Biofisica, Consiglio Nazionale delle Ricerche, Via De Marini 6, 16149 Genova (Italy)

    2012-07-06

    Highlights: Black-Right-Pointing-Pointer CFTR mutations produce cystic fibrosis. Black-Right-Pointing-Pointer Chloride transport depends on the regulatory domain phosphorylation. Black-Right-Pointing-Pointer Regulatory domain is intrinsically disordered. Black-Right-Pointing-Pointer Secondary structure and protein stability change upon phosphorylation. -- Abstract: The regulatory domain (RD) of the cystic fibrosis transmembrane conductance regulator (CFTR), the defective protein in cystic fibrosis, is the region of the channel that regulates the CFTR activity with multiple phosphorylation sites. This domain is an intrinsically disordered protein, characterized by lack of stable or unique tertiary structure. The disordered character of a protein is directly correlated with its function. The flexibility of RD may be important for its regulatory role: the continuous conformational change may be necessary for the progressive phosphorylation, and thus activation, of the channel. However, the lack of a defined and stable structure results in a considerable limitation when trying to in build a unique molecular model for the RD. Moreover, several evidences indicate significant structural differences between the native, non-phosphorylated state, and the multiple phosphorylated state of the protein. The aim of our work is to provide data to describe the conformations and the thermodynamic properties in these two functional states of RD. We have done the circular dichroism (CD) spectra in samples with a different degree of phosphorylation, from the non-phosphorylated state to a bona fide completely phosphorylated state. Analysis of CD spectra showed that the random coil and {beta}-sheets secondary structure decreased with the polypeptide phosphorylation, at expenses of an increase of {alpha}-helix. This observation lead to interpret phosphorylation as a mechanism favoring a more structured state. We also studied the thermal denaturation curves of the protein in the two

  2. Thermodynamic study of the native and phosphorylated regulatory domain of the CFTR

    International Nuclear Information System (INIS)

    Marasini, Carlotta; Galeno, Lauretta; Moran, Oscar

    2012-01-01

    Highlights: ► CFTR mutations produce cystic fibrosis. ► Chloride transport depends on the regulatory domain phosphorylation. ► Regulatory domain is intrinsically disordered. ► Secondary structure and protein stability change upon phosphorylation. -- Abstract: The regulatory domain (RD) of the cystic fibrosis transmembrane conductance regulator (CFTR), the defective protein in cystic fibrosis, is the region of the channel that regulates the CFTR activity with multiple phosphorylation sites. This domain is an intrinsically disordered protein, characterized by lack of stable or unique tertiary structure. The disordered character of a protein is directly correlated with its function. The flexibility of RD may be important for its regulatory role: the continuous conformational change may be necessary for the progressive phosphorylation, and thus activation, of the channel. However, the lack of a defined and stable structure results in a considerable limitation when trying to in build a unique molecular model for the RD. Moreover, several evidences indicate significant structural differences between the native, non-phosphorylated state, and the multiple phosphorylated state of the protein. The aim of our work is to provide data to describe the conformations and the thermodynamic properties in these two functional states of RD. We have done the circular dichroism (CD) spectra in samples with a different degree of phosphorylation, from the non-phosphorylated state to a bona fide completely phosphorylated state. Analysis of CD spectra showed that the random coil and β-sheets secondary structure decreased with the polypeptide phosphorylation, at expenses of an increase of α-helix. This observation lead to interpret phosphorylation as a mechanism favoring a more structured state. We also studied the thermal denaturation curves of the protein in the two conditions, monitoring the changes of the mean residue ellipticity measured at 222 nm as a function of temperature

  3. Domain cooperativity in the β1a subunit is essential for dihydropyridine receptor voltage sensing in skeletal muscle.

    Science.gov (United States)

    Dayal, Anamika; Bhat, Vinayakumar; Franzini-Armstrong, Clara; Grabner, Manfred

    2013-04-30

    The dihydropyridine receptor (DHPR) β1a subunit is crucial for enhancement of DHPR triad expression, assembly of DHPRs in tetrads, and elicitation of DHPRα1S charge movement--the three prerequisites of skeletal muscle excitation-contraction coupling. Despite the ability to fully target α1S into triadic junctions and tetradic arrays, the neuronal isoform β3 was unable to restore considerable charge movement (measure of α1S voltage sensing) upon expression in β1-null zebrafish relaxed myotubes, unlike the other three vertebrate β-isoforms (β1a, β2a, and β4). Thus, we used β3 for chimerization with β1a to investigate whether any of the five distinct molecular regions of β1a is dominantly involved in inducing the voltage-sensing function of α1S. Surprisingly, systematic domain swapping between β1a and β3 revealed a pivotal role of the src homology 3 (SH3) domain and C terminus of β1a in charge movement restoration. More interestingly, β1a SH3 domain and C terminus, when simultaneously engineered into β3 sequence background, were able to fully restore charge movement together with proper intracellular Ca(2+) release, suggesting cooperativity of these two domains in induction of the α1S voltage-sensing function in skeletal muscle excitation-contraction coupling. Furthermore, substitution of a proline by alanine in the putative SH3-binding polyproline motif in the proximal C terminus of β1a (also of β2a and β4) fully obstructed α1S charge movement. Consequently, we postulate a model according to which β subunits, probably via the SH3-C-terminal polyproline interaction, adapt a discrete conformation required to modify the α1S conformation apt for voltage sensing in skeletal muscle.

  4. Brain connectivity study of joint attention using frequency-domain optical imaging technique

    Science.gov (United States)

    Chaudhary, Ujwal; Zhu, Banghe; Godavarty, Anuradha

    2010-02-01

    Autism is a socio-communication brain development disorder. It is marked by degeneration in the ability to respond to joint attention skill task, from as early as 12 to 18 months of age. This trait is used to distinguish autistic from nonautistic populations. In this study, diffuse optical imaging is being used to study brain connectivity for the first time in response to joint attention experience in normal adults. The prefrontal region of the brain was non-invasively imaged using a frequency-domain based optical imager. The imaging studies were performed on 11 normal right-handed adults and optical measurements were acquired in response to joint-attention based video clips. While the intensity-based optical data provides information about the hemodynamic response of the underlying neural process, the time-dependent phase-based optical data has the potential to explicate the directional information on the activation of the brain. Thus brain connectivity studies are performed by computing covariance/correlations between spatial units using this frequency-domain based optical measurements. The preliminary results indicate that the extent of synchrony and directional variation in the pattern of activation varies in the left and right frontal cortex. The results have significant implication for research in neural pathways associated with autism that can be mapped using diffuse optical imaging tools in the future.

  5. Studies in astronomical time series analysis. I - Modeling random processes in the time domain

    Science.gov (United States)

    Scargle, J. D.

    1981-01-01

    Several random process models in the time domain are defined and discussed. Attention is given to the moving average model, the autoregressive model, and relationships between and combinations of these models. Consideration is then given to methods for investigating pulse structure, procedures of model construction, computational methods, and numerical experiments. A FORTRAN algorithm of time series analysis has been developed which is relatively stable numerically. Results of test cases are given to study the effect of adding noise and of different distributions for the pulse amplitudes. A preliminary analysis of the light curve of the quasar 3C 272 is considered as an example.

  6. Magneto-optical study of domain wall dynamics and giant Barkhausen jump in magnetic microwires

    International Nuclear Information System (INIS)

    Chizhik, A.; Zhukov, A.; Blanco, J.M.; Gonzalez, J.

    2012-01-01

    Investigation of surface domain walls motion in Co-rich magnetic microwires has been performed in circular and axial magnetic fields. The dc axial magnetic field acceleration of the domain wall motion related to the influence of the axial field on the structure of the moving domain wall has been discovered. Pulsed axial magnetic field induced unidirectional motion of surface domain wall also has been found.

  7. Domains associated with successful quality improvement in healthcare - a nationwide case study.

    Science.gov (United States)

    Brandrud, Aleidis Skard; Nyen, Bjørnar; Hjortdahl, Per; Sandvik, Leiv; Helljesen Haldorsen, Gro Sævil; Bergli, Maria; Nelson, Eugene C; Bretthauer, Michael

    2017-09-13

    There is a distinct difference between what we know and what we do in healthcare: a gap that is impairing the quality of the care and increasing the costs. Quality improvement efforts have been made worldwide by learning collaboratives, based on recognized continual improvement theory with limited scientific evidence. The present study of 132 quality improvement projects in Norway explores the conditions for improvement from the perspectives of the frontline healthcare professionals, and evaluates the effectiveness of the continual improvement method. An instrument with 25 questions was developed on prior focus group interviews with improvement project members who identified features that may promote or inhibit improvement. The questionnaire was sent to 189 improvement projects initiated by the Norwegian Medical Association, and responded by 70% (132) of the improvement teams. A sub study of their final reports by a validated instrument, made us able to identify the successful projects and compare their assessments with the assessments of the other projects. A factor analysis with Varimax rotation of the 25 questions identified five domains. A multivariate regression analysis was used to evaluate the association with successful quality improvements. Two of the five domains were associated with success: Measurement and Guidance (p = 0.011), and Professional environment (p = 0.015). The organizational leadership domain was not associated with successful quality improvements (p = 0.26). Our findings suggest that quality improvement projects with good guidance and focus on measurement for improvement have increased likelihood of success. The variables in these two domains are aligned with improvement theory and confirm the effectiveness of the continual improvement method provided by the learning collaborative. High performing professional environments successfully engaged in patient-centered quality improvement if they had access to: (a) knowledge of best

  8. Micromagnetic study of single-domain FePt nanocrystals overcoated with silica

    International Nuclear Information System (INIS)

    Hyun, Changbae; Lee, Doh C; Korgel, Brian A; Lozanne, Alex de

    2007-01-01

    Chemically-synthesized FePt nanocrystals must be annealed at a high temperature (>550 deg. C) to induce the hard ferromagnetic L 1 0 phase. Unfortunately, the organic stabilizer covering these nanocrystals degrades at these temperatures and the nanocrystals sinter, resulting in the loss of control over nanocrystal size and separation in the film. We have developed a silica overcoating strategy to prevent nanocrystal sintering. In this study, 6 nm diameter FePt nanocrystals were coated with 17 nm thick shells of silica using an inverse micelle process. Magnetization measurements of the annealed FePt-SiO 2 nanocrystals indicate ferromagnetism with a high coercivity at room temperature. Magnetic force microscopy (MFM) results show that the film composed of nanocrystals behaves as a dipole after magnetization by an 8 T external field. The individual nanocrystals are modelled as single-domain particles with random crystallographic orientations. We propose that the interparticle magnetic dipole interaction is weaker than the magnetocrystalline energy in the remanent state, leading to an unusual material with no magnetic anisotropy and no domains. Films of these nanoparticles are promising candidates for magnetic media with a data storage density of ∼Tb/in 2

  9. Study of Anterior Chamber Aqueous Tube Shunt by Fourier-Domain Optical Coherence Tomography

    Directory of Open Access Journals (Sweden)

    Chunhui Jiang

    2012-01-01

    Full Text Available Purpose. This cross-sectional, observational study used Fourier-domain optical coherence tomography (OCT to examine the position, patency, and the interior entrance site of anterior chamber (AC aqueous tube shunts. Methods. The OCT, slitlamp biomicroscopy, and gonioscopy findings of 23 eyes of 18 patients with AC shunts were collected and compared. Results. OCT images demonstrated the shunt position and patency in all 23 eyes, and the details of the AC entrance in 16 eyes. The position of the tube varied, with the majority (14/23 on the surface of the iris. The exact position of the AC entrance relative to Schwalbe’s line (SL could be determined in 9 eyes (posterior to SL in 7 eyes, anterior in 2 eyes. At the AC entrance, growth of fibrous scar tissue was present between the tube and the corneal endothelium in all 16 eyes in which the entrance could be clearly visualized. It’s a new finding that could not be visualized by slitlamp examination or lower resolution OCT. Conclusion. Compared to slitlamp examination, Fourier-domain OCT of AC tube shunts provided more detailed anatomic information regarding the insertion level relative to SL, scar tissue between the tube and the corneal endothelium, and patency of the tube opening.

  10. A scientometric study of general internal medicine domain among muslim countries of middle East (1991 - 2011).

    Science.gov (United States)

    Hodhodinezhad, Niloofar; Zahedi, Razieh; Ashrafi-rizzi, Hassan; Shams, Asadollah

    2013-03-01

    The position of General Internal Medicine in the Islamic countries in the Middle East has been investigated in the present study. The scientific productions of the countries in the area on Web of science database during 1990-2011 constitute were examined. The result of the survey showed that the share of these countries in world scientific productions is very low. Turkey, Saudi Arabia and Iran are the first to third ones in this domain in order. In view of annual growth rate, Kuwait having high growth rate, is the first one. Libya and Syria are the next ones. The scientific poverty line of Islamic countries in the area was surveyed. The result showed that in view of the scientific poverty line, the highest is Kuwait with the population of 0.04 percent of the world. Next to it, Saudi Arabia and Bahrain are the second and third ones. The results of this research showed that the share of Islamic countries in the Middle East in scientific production of this medicine domain is very low. It needs to be paid more attention by the countries in the area.

  11. Diffusion mediated coagulation and fragmentation based study of domain formation in lipid bilayer membrane

    Energy Technology Data Exchange (ETDEWEB)

    Rao, Laxminarsimha V., E-mail: laxman@iitk.ac.in [Mechanics and Applied Mathematics Group, Department of Mechanical Engineering, Indian Institute of Technology Kanpur, Kanpur 208016 (India); Roy, Subhradeep [Department of Biomedical Engineering and Mechanics (MC 0219), Virginia Tech, 495 Old Turner Street, Blacksburg, VA 24061 (United States); Das, Sovan Lal [Mechanics and Applied Mathematics Group, Department of Mechanical Engineering, Indian Institute of Technology Kanpur, Kanpur 208016 (India)

    2017-01-15

    We estimate the equilibrium size distribution of cholesterol rich micro-domains on a lipid bilayer by solving Smoluchowski equation for coagulation and fragmentation. Towards this aim, we first derive the coagulation kernels based on the diffusion behaviour of domains moving in a two dimensional membrane sheet, as this represents the reality better. We incorporate three different diffusion scenarios of domain diffusion into our coagulation kernel. Subsequently, we investigate the influence of the parameters in our model on the coagulation and fragmentation behaviour. The observed behaviours of the coagulation and fragmentation kernels are also manifested in the equilibrium domain size distribution and its first moment. Finally, considering the liquid domains diffusing in a supported lipid bilayer, we fit the equilibrium domain size distribution to a benchmark solution.

  12. Docking Studies of Binding of Ethambutol to the C-Terminal Domain of the Arabinosyltransferase from Mycobacterium tuberculosis

    Directory of Open Access Journals (Sweden)

    Guillermo Salgado-Moran

    2013-01-01

    Full Text Available The binding of ethambutol to the C-terminal domain of the arabinosyltransferase from Mycobacterium tuberculosis was studied. The analysis was performed using an in silico approach in order to find out, by docking calculations and energy descriptors, the conformer of Ethambutol that forms the most stable complex with the C-terminal domain of arabinosyltransferase. The complex shows that location of the Ethambutol coincides with the cocrystallization ligand position and that amino acid residues ASH1051, ASN740, ASP1052, and ARG1055 should be critical in the binding of Ethambutol to C-terminal domain EmbC.

  13. Structural Studies of the SET Domain from RIZ1 Tumor Suppressor

    Energy Technology Data Exchange (ETDEWEB)

    Briknarova, Klara; Zhou, Xinliang; Satterthwait, Arnold C.; Hoyt, David W.; Ely, Kathryn R.; Huang, Shi

    2008-02-15

    Histone lysine methyltransferases (HKMTs) are involved in regulation of chromatin structure, and, as such, are important for longterm gene activation and repression that is associated with cell memory and establishment of cell-type specific transcriptional programs. Most HKMTs contain a SET domain, which is responsible for their catalytic activity. RIZ1 is a transcription regulator and tumor suppressor that catalyzes methylation of lysine 9 of histone H3 and contains a rather distinct SET domain. Similar SET domains, sometimes refererred to as PR (PRDI-BF1 and RIZ1 homology) domains, are also found in other proteins including Blimp-1/PRDI-BF1, MDS1-EVI1 and Meisetz. We determined the solution structure of the PR domain from RIZ1 and characterized its interaction with S-adenosyl homocysteine (SAH) and a peptide from histone H3. Despite low sequence identity with canonical SET domains, the PR domain displays a typical SET fold including a pseudo-knot at the C-terminus. The N-flanking sequence of RIZ1 PR domain adopts a novel conformation and interacts closely with the SET fold. The C-flanking sequence contains an α-helix that exhibits higher mobility than the SET fold and points away from the protein face that harbors active site in other SET domains. Residues that interact with the methylation cofactor in SET domains are not conserved in RIZ1 or other PR domains, and the SET fold of RIZ1 does not bind SAH. However, the PR domain of RIZ1 interacts specifically with a synthetic peptide comprising residues 1-20 of histone H3.

  14. Sedimentation in Particulate Aqueous Suspensions as studied by means of Dielectric Time Domain Spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Pettersen, Bjoernar Hauknes

    1997-12-31

    Many problems in offshore oil production and multiphase transport are related to surface and colloid chemistry. This thesis applies dielectric spectroscopy as an experimental technique to study the behaviour of particle suspensions in polar media. The thesis opens with an introduction to suspensions and time domain dielectric spectroscopy. It then investigates the dielectric properties of silica and alumina dispersed in polar solvents. It is found that theoretical models can be used to calculate the volume fraction disperse phase in the suspension and that the particle sedimentation depends on the wetting of the particles, charge on the particle surface and viscosity of the solvent, and that this dependency can be measured by time domain dielectric spectroscopy. When the surface properties of silica and alumina particles were modified by coating them with a non-ionic polymer and a non-ionic surfactant, then different degrees of packing in the sedimented phase at the bottom of the sedimentation vessel occurred. Chemometrical methods on the synthesis of monodisperse silica particles were used to investigate what factors influence the particle size. It turned out that it is insufficient to consider only main variables when discussing the results of the synthesis. By introducing interaction terms, the author could explain the variation in the size of particles synthesized. The difference in the sedimentation rate of monodisperse silica particles upon variation of volume fraction particles, pH, salinity, amount of silanol groups at the particle surface and temperature was studied. The cross interactions play an important role and a model explaining the variation in sedimentation is introduced. Finally, magnetic particles dispersed in water and in an external magnetic field were used to study the impact on the sedimentation due to the induced flocculation. 209 refs., 90 figs., 9 tabs.

  15. Time-domain vibrational study on defects in ion-irradiated crystal

    International Nuclear Information System (INIS)

    Kitajima, M.

    2003-01-01

    We have studied the effects of point defects on coherent phonons in ion-implanted bismuth and graphite. Ultrafast dynamics of coherent phonons and photo-generated carriers in the femtosecond time-domain have been investigated by means of pump-probe reflectivity measurements. Point defects are introduced by irradiating graphite with 5 keV He + ions. For Bi the dephasing rate of the A 1g phonon increases linearly with increasing ion dose, which is explained by the additional dephasing process of the coherent phonon originated from scattering of phonons by the defects. For graphite, introduction of the defects enhances the carrier relaxation by opening a decay channel via vacancy-states, which competes efficiently with carrier-phonon scattering. The coherent acoustic phonon relaxation is also accelerated due to an additional scattering by defects. The linear fluence-dependence of the decay rate is understood as scattering of propagating acoustic phonon by single vacancies. (author)

  16. Studies in astronomical time series analysis: Modeling random processes in the time domain

    Science.gov (United States)

    Scargle, J. D.

    1979-01-01

    Random process models phased in the time domain are used to analyze astrophysical time series data produced by random processes. A moving average (MA) model represents the data as a sequence of pulses occurring randomly in time, with random amplitudes. An autoregressive (AR) model represents the correlations in the process in terms of a linear function of past values. The best AR model is determined from sampled data and transformed to an MA for interpretation. The randomness of the pulse amplitudes is maximized by a FORTRAN algorithm which is relatively stable numerically. Results of test cases are given to study the effects of adding noise and of different distributions for the pulse amplitudes. A preliminary analysis of the optical light curve of the quasar 3C 273 is given.

  17. Study on viscosity of conventional and polymer modified asphalt binders in steady and dynamic shear domain

    Science.gov (United States)

    Saboo, Nikhil; Singh, Bhupendra; Kumar, Praveen; Vikram, Durgesh

    2018-02-01

    This study focuses on evaluating the flow behavior of conventional and polymer modified asphalt binders in steady- and dynamic-shear domain, for a temperature range of 20-70 °C, using a Dynamic Shear Rheometer (DSR). Steady-shear viscosity and frequency sweep tests were carried out on two conventional (VG 10 and VG 30) and two polymer (SBS and EVA) modified asphalt binders. Applicability of the Cox-Merz principle was evaluated and complex viscosity master curves were analyzed at five different reference temperatures. Cross model was used to simulate the complex viscosity master curves at different temperatures. It was found that asphalt binders exhibited shear-thinning behavior at all the test temperatures. The critical shear rate increased with increase in temperature and was found to be lowest for plastomeric modified asphalt binder. The Cox-Merz principle was found to be valid in the zero-shear viscosity (ZSV) domain and deviated at higher frequency/shear rate for all the binders. Results from the study indicated that the ratio of ZSV can be successfully used as shift factors for construction of master curves at different reference temperatures. Cross model was found to be suitable in simulating the complex viscosity master curves at all the test temperatures. Analysis of model parameters indicated that a strong relationship exists between ZSV and the critical shear rate. ZSV and critical shear rate varied exponentially with temperature. This relationship was used to propose a simple equation for assessing the shift factors for construction of master curves.

  18. Study of goldfish (Carassius auratus) growth hormone structure-function relationship by domain swapping.

    Science.gov (United States)

    Chan, Y H; Cheng, C H K; Chan, K M

    2007-03-01

    Using goldfish as a model, the structure-function relationship of goldfish growth hormone was studied using the strategy of homologous domain swapping. Chimeric mutants were constructed by exchanging homologous regions between goldfish growth hormone (gfGH II) and goldfish prolactin (gfPRL) with their cloned complementary DNAs. Six mutants, with their domain-swapped, were generated to have different combinations of three target regions, including the helix a, helix d and the large section in between these helices (possess the helices b, c and other random coiled regions). After expression in E. coli and refolding, these mutants were characterized by using competitive receptor binding assay (RRA) and growth hormone responding promoter activation assay. The different activity profiles of mutants in Spi 2.1 gene promoter assays from that in RRA shows that, for gfGH, receptor binding dose not confer receptor signal activations. When either helices a or d of gfGH was maintained with other helices replaced by their gfPRL counterparts, both receptor binding and hence gene activation activities are reduced. In mutants with helices b and c in gfGH maintained, containing the gfGH middle section, and helices a and d swapped with gfPRL, the had reduced RRA activities but the promoter activation activities retained. In conclusion, as in the case of human GH, the gfGH molecule possesses two functional sites: one of them is composed of discontinuous epitopes located on the target regions of this study and is for receptor binding; another site is located on the middle section of the molecule that helices a and d are not involved, and it is for activation of GH receptor and intracellular signals.

  19. Pleckstrin Homology Domain Diffusion in Dictyostelium Cytoplasm Studied Using Fluorescence Correlation Spectroscopy

    NARCIS (Netherlands)

    Engel, Ruchira; Hink, Mark A.; Bosgraaf, Leonard; Haastert, Peter J.M. van; Visser, Antonie J.W.G.

    2004-01-01

    The translocation of pleckstrin homology (PH) domain-containing proteins from the cytoplasm to the plasma membrane plays an important role in the chemotaxis mechanism of Dictyostelium cells. The diffusion of three PH domain-green fluorescent protein (GFP) fusions (PH2-GFP, PH10-GFP, and PH-CRAC

  20. Pleckstrin homology domain diffusion in Dictyostelium cytoplasm studied using fluorescence correlation spectroscopy

    NARCIS (Netherlands)

    Ruchira, A.; Hink, M.A.; Bosgraaf, L.; Haastert, van P.J.M.; Visser, A.J.W.G.

    2004-01-01

    The translocation of pleckstrin homology (PH) domain-containing proteins from the cytoplasm to the plasma membrane plays an important role in the chemotaxis mechanism of Dictyostelium cells. The diffusion of three PH domain-green fluorescent protein (GFP) fusions (PH2-GFP, PH10-GFP, and PH-CRAC

  1. Using Semantic Web technologies for the generation of domain-specific templates to support clinical study metadata standards.

    Science.gov (United States)

    Jiang, Guoqian; Evans, Julie; Endle, Cory M; Solbrig, Harold R; Chute, Christopher G

    2016-01-01

    The Biomedical Research Integrated Domain Group (BRIDG) model is a formal domain analysis model for protocol-driven biomedical research, and serves as a semantic foundation for application and message development in the standards developing organizations (SDOs). The increasing sophistication and complexity of the BRIDG model requires new approaches to the management and utilization of the underlying semantics to harmonize domain-specific standards. The objective of this study is to develop and evaluate a Semantic Web-based approach that integrates the BRIDG model with ISO 21090 data types to generate domain-specific templates to support clinical study metadata standards development. We developed a template generation and visualization system based on an open source Resource Description Framework (RDF) store backend, a SmartGWT-based web user interface, and a "mind map" based tool for the visualization of generated domain-specific templates. We also developed a RESTful Web Service informed by the Clinical Information Modeling Initiative (CIMI) reference model for access to the generated domain-specific templates. A preliminary usability study is performed and all reviewers (n = 3) had very positive responses for the evaluation questions in terms of the usability and the capability of meeting the system requirements (with the average score of 4.6). Semantic Web technologies provide a scalable infrastructure and have great potential to enable computable semantic interoperability of models in the intersection of health care and clinical research.

  2. Targeting Self-Binding Peptides as a Novel Strategy To Regulate Protein Activity and Function: A Case Study on the Proto-oncogene Tyrosine Protein Kinase c-Src.

    Science.gov (United States)

    Bai, Zhengya; Hou, Shasha; Zhang, Shilei; Li, Zhongyan; Zhou, Peng

    2017-04-24

    Previously, we have reported a new biomolecular phenomenon spanning between protein folding and binding, termed as self-binding peptides (SBPs), where a short peptide segment in monomeric protein functions as a molecular switch by dynamically binding to/unbinding from its cognate domain in the monomer (Yang et al. J. Chem. Inf. 2015, 55, 329-342). Here, we attempt to raise the SBP as a new class of druggable targets to regulate the biological activity and function of proteins. A case study was performed on the proto-oncogene nonreceptor tyrosine kinase, c-Src, which contains two SBPs that bind separately to SH3 and SH2 domains of the kinase. State-of-the-art molecular dynamics (MD) simulations and post binding energetics analysis revealed that disrupting the kinase-intramolecular interactions of SH3 and SH2 domains with their cognate SBP ligands can result in totally different effects on the structural dynamics of c-Src kinase architecture; targeting the SH2 domain unlocks the autoinhibitory form of the kinase-this is very similar to the pTyr527 dephosphorylation that functionally activates the kinase, whereas targeting the SH3 domain can only release the domain from the tightly packed kinase but has a moderate effect on the kinase activity. Subsequently, based on the cognate SBP sequence we computationally designed a number of SH2-binding phosphopeptides using a motif grafting strategy. Fluorescence polarization (FP) assay observed that most of the designed phosphopeptides have higher binding affinity to SH2 domain as compared to the native SBP segment (K d = 53 nM). Kinase assay identified a typical dose-response relationship of phosphopeptides against kinase activation, substantiating that disruption of SH2-SBP interaction can mimic c-Src dephosphorylation and activate the kinase. Two rationally designed phosphopeptides, namely EPQpYEEIEN and EPQpYEELEN, were determined as strong binders of SH2 domain (K d = 8.3 and 15 nM, respectively) and potent activators of

  3. Neutron diffraction study of ordering of atoms and antiphase domains in titanium carbohydrides

    International Nuclear Information System (INIS)

    Khidirov, I.; Mirzaev, B.B.; Sultanova, S.Kh.; Mukhtarova, N.N.; Getmanskiy, V.V.

    2004-01-01

    Full text: As a result of neutron diffraction study of titanium carbon hydrides of a number of compositions at the lower limit of the carbon homogeneity region (TiC 0.47 H 0.22 , TiC 0.47 H 0.19 , TiC 0.47 H 0.07 , TiC 0.50 H 0.21 ) after by heat treatment using special regime for preventing exit of hydrogen out of the lattice, five temperature ranges of temperature of structural changes are found out. 1. T ≥ 1200 o C, at which titanium carbon hydrides have disordered cubic structure, is described within the framework of sp. gr. Fd3m, where the carbon atoms occupy octahedral interstices and the hydrogen atoms - tetrahedral ones. 2. 1000 o C ≤ T ≤ 1100 o C: it is still observed the disordered cubic structure in which the hydrogen atoms statistically are arranged on both octahedral and tetrahedral interstices. 3. 800 0 C ≤ T ≤ 1000 o C: formation of long-range order is observed. Crystal structure of the ordered phase is described within the framework of sp. gr. Fd3m, where the carbon atoms occupy one type of octahedral interstices 16 (c) and the hydrogen atoms - the other type of octahedral interstices 16 (d). 4. 600 o C ≤ T ≤ 800 o C: the decay of ordered cubic phase with segregation of α-Ti is observed. 5. T≤ 475 o C: the formation of metastable ordered cubic phase with the formation of periodic antiphase domains is observed, at these temperatures process of the decay is hindered. It should be noted that the formation of ordered periodic antiphase domains (long-period structure) in the interstitial phase is found for the first time. This work was supported by the Center of Science and Technology of the Republic of Uzbekistan (contract No F-2.1.2)

  4. Neutron diffraction study of ordering of atoms and antiphase domains in titanium carbohydrides

    International Nuclear Information System (INIS)

    Khidirov, I.; Mirzaev, B.B.; Sultanova, S.Kh.; Mukhtarova, N.N.; Getmanskiy, V.V.

    2004-01-01

    As a result of neutron diffraction study of titanium carbon hydrides of a number of compositions at the lower limit of the carbon homogeneity region (TiC 0.47 H 0.22 , TiC 0.47 H 0.19 , TiC 0.47 H 0.07 , TiC 0.50 H 0.21 ) after by heat treatment using special regime for preventing exit of hydrogen out of the lattice, five temperature ranges of temperature of structural changes are found out. 1. T ≥ 1200 o C, at which titanium carbon hydrides have disordered cubic structure, is described within the framework of sp. gr. Fd3m, where the carbon atoms occupy octahedral interstices and the hydrogen atoms - tetrahedral ones. 2. 1000 o C ≤ T ≤ 1100 o C: it is still observed the disordered cubic structure in which the hydrogen atoms statistically are arranged on both octahedral and tetrahedral interstices. 3. 800 0 C ≤ T ≤ 1000 o C: formation of long-range order is observed. Crystal structure of the ordered phase is described within the framework of sp. gr. Fd3m, where the carbon atoms occupy one type of octahedral interstices 16 (c) and the hydrogen atoms - the other type of octahedral interstices 16 (d). 4. 600 o C ≤ T ≤ 800 o C: the decay of ordered cubic phase with segregation of α-Ti is observed. 5. T≤ 475 o C: the formation of metastable ordered cubic phase with the formation of periodic antiphase domains is observed, at these temperatures process of the decay is hindered. It should be noted that the formation of ordered periodic antiphase domains (long-period structure) in the interstitial phase is found for the first time. This work was supported by the Center of Science and Technology of the Republic of Uzbekistan (contract No F-2.1.2). (author)

  5. The conserved WW-domain binding sites in Dystroglycan C-terminus are essential but partially redundant for Dystroglycan function

    Directory of Open Access Journals (Sweden)

    Deng W-M

    2009-02-01

    Full Text Available Abstract Background Dystroglycan (Dg is a transmembrane protein that is a part of the Dystrophin Glycoprotein Complex (DGC which connects the extracellular matrix to the actin cytoskeleton. The C-terminal end of Dg contains a number of putative SH3, SH2 and WW domain binding sites. The most C-terminal PPXY motif has been established as a binding site for Dystrophin (Dys WW-domain. However, our previous studies indicate that both Dystroglycan PPXY motives, WWbsI and WWbsII can bind Dystrophin protein in vitro. Results We now find that both WW binding sites are important for maintaining full Dg function in the establishment of oocyte polarity in Drosophila. If either WW binding site is mutated, the Dg protein can still be active. However, simultaneous mutations in both WW binding sites abolish the Dg activities in both overexpression and loss-of-function oocyte polarity assays in vivo. Additionally, sequence comparisons of WW binding sites in 12 species of Drosophila, as well as in humans, reveal a high level of conservation. This preservation throughout evolution supports the idea that both WW binding sites are functionally required. Conclusion Based on the obtained results we propose that the presence of the two WW binding sites in Dystroglycan secures the essential interaction between Dg and Dys and might further provide additional regulation for the cytoskeletal interactions of this complex.

  6. Crystal structure of the G3BP2 NTF2-like domain in complex with a canonical FGDF motif peptide.

    Science.gov (United States)

    Kristensen, Ole

    2015-11-06

    The crystal structure of the NTF2-like domain of the human Ras GTPase SH3 Binding Protein (G3BP), isoform 2, was determined at a resolution of 2.75 Å in complex with a peptide containing a FGDF sequence motif. The overall structure of the protein is highly similar to the homodimeric N-terminal domains of the G3BP1 and Rasputin proteins. Recently, a subset of G3BP interacting proteins was recognized to share a common sequence motif, FGDF. The most studied binding partners, USP10 and viral nsP3, interfere with essential G3BP functions related to assembly of cellular stress granules. Reported molecular modeling suggested that FGDF-motif containing peptides bind in an extended conformation into a hydrophobic groove on the surface of the G3BP NTF2-like domain in a manner similar to the known binding of FxFG nucleoporin repeats. The results in this paper provide evidence for a different binding mode. The FGDF peptide binds and changes conformation of the protruding N-terminal residues by providing hydrophobic interactions to a symmetry related molecule that facilitated crystallization of the G3BP2 isoform. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. First-in-human pilot study of a spatial frequency domain oxygenation imaging system

    Science.gov (United States)

    Gioux, Sylvain; Mazhar, Amaan; Lee, Bernard T.; Lin, Samuel J.; Tobias, Adam M.; Cuccia, David J.; Stockdale, Alan; Oketokoun, Rafiou; Ashitate, Yoshitomo; Kelly, Edward; Weinmann, Maxwell; Durr, Nicholas J.; Moffitt, Lorissa A.; Durkin, Anthony J.; Tromberg, Bruce J.; Frangioni, John V.

    2011-08-01

    Oxygenation measurements are widely used in patient care. However, most clinically available instruments currently consist of contact probes that only provide global monitoring of the patient (e.g., pulse oximetry probes) or local monitoring of small areas (e.g., spectroscopy-based probes). Visualization of oxygenation over large areas of tissue, without a priori knowledge of the location of defects, has the potential to improve patient management in many surgical and critical care applications. In this study, we present a clinically compatible multispectral spatial frequency domain imaging (SFDI) system optimized for surgical oxygenation imaging. This system was used to image tissue oxygenation over a large area (16×12 cm) and was validated during preclinical studies by comparing results obtained with an FDA-approved clinical oxygenation probe. Skin flap, bowel, and liver vascular occlusion experiments were performed on Yorkshire pigs and demonstrated that over the course of the experiment, relative changes in oxygen saturation measured using SFDI had an accuracy within 10% of those made using the FDA-approved device. Finally, the new SFDI system was translated to the clinic in a first-in-human pilot study that imaged skin flap oxygenation during reconstructive breast surgery. Overall, this study lays the foundation for clinical translation of endogenous contrast imaging using SFDI.

  8. Concrete domains

    OpenAIRE

    Kahn, G.; Plotkin, G.D.

    1993-01-01

    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 of evaluation.

  9. Studying Mechanosensitivity of Two-Pore Domain K+ Channels in Cellular and Reconstituted Proteoliposome Membranes.

    Science.gov (United States)

    Del Mármol, Josefina; Rietmeijer, Robert A; Brohawn, Stephen G

    2018-01-01

    Mechanical force sensation is fundamental to a wide breadth of biology from the classic senses of touch, pain, hearing, and balance to less conspicuous sensations of proprioception, blood pressure, and osmolarity and basic aspects of cell growth, differentiation, and development. These diverse and essential systems use force-gated (or mechanosensitive) ion channels that convert mechanical stimuli into cellular electrical signals. TRAAK, TREK1, and TREK2 are K + -selective ion channels of the two-pore domain K + (K2P) family that are mechanosensitive: they are gated open by increasing membrane tension. TRAAK and TREK channels are thought to play roles in somatosensory and other mechanosensory processes in neuronal and non-neuronal tissues. Here, we present protocols for three assays to study mechanical activation of these channels in cell membranes: (1) cell swelling, (2) cell poking, and (3) patched membrane stretching. Patched membrane stretching is also applicable to the study of mechanosensitive K2P channel activity in a cell-free system and a procedure for proteoliposome reconstitution and patching is also presented. These approaches are also readily applicable to the study of other mechanosensitive ion channels.

  10. Business alignment in the procurement domain: a study of antecedents and determinants of supply chain performance

    Directory of Open Access Journals (Sweden)

    Patrick Mikalef

    2014-01-01

    Full Text Available With organizations now placing an increasing amount on attention on the management of their supply chain activities, the role of Information Technology (IT in supporting these operations has been put in the spotlight. In spite of extensive research examining how IT can be employed in various activities of supply chain management, the majority of studies are limited in identifying enablers and inhibitors of adoption. Empirical studies examining post-adoption conditions that facilitate performance improvement still remain scarce. In this study we focus on procurement as part of the supply chain management activities. We apply the business-IT alignment perspective to the domain of procurement, and examine how certain organizational factors impact the attainment of this state. Additionally, we research the effect that procurement alignment has on supply chain management performance. In order to do so, we apply Partial Least Squares (PLS analysis on a sample of 172 European companies. We find that firms that opt for a centralized governance structure, as well as larger firms, are more likely to attain a state of procurement alignment. Furthermore, our results empirically support the statement that procurement alignment is positively correlated with operational efficiency and competitive performance of the supply chain.

  11. Domain Engineering

    Science.gov (United States)

    Bjørner, Dines

    Before software can be designed we must know its requirements. Before requirements can be expressed we must understand the domain. So it follows, from our dogma, that we must first establish precise descriptions of domains; then, from such descriptions, “derive” at least domain and interface requirements; and from those and machine requirements design the software, or, more generally, the computing systems.

  12. Linguistic explanation and domain specialization: a case study in bound variable anaphora.

    Science.gov (United States)

    Adger, David; Svenonius, Peter

    2015-01-01

    The core question behind this Frontiers research topic is whether explaining linguistic phenomena requires appeal to properties of human cognition that are specialized to language. We argue here that investigating this issue requires taking linguistic research results seriously, and evaluating these for domain-specificity. We present a particular empirical phenomenon, bound variable interpretations of pronouns dependent on a quantifier phrase, and argue for a particular theory of this empirical domain that is couched at a level of theoretical depth which allows its principles to be evaluated for domain-specialization. We argue that the relevant principles are specialized when they apply in the domain of language, even if analogs of them are plausibly at work elsewhere in cognition or the natural world more generally. So certain principles may be specialized to language, though not, ultimately, unique to it. Such specialization is underpinned by ultimately biological factors, hence part of UG.

  13. Thermal denaturation of protein studied by terahertz time-domain spectroscopy

    Science.gov (United States)

    Fu, Xiuhua; Li, Xiangjun; Liu, Jianjun; Du, Yong; Hong, Zhi

    2012-12-01

    In this study, the absorption spectra of native or thermal protein were measured in 0.2-1.4THz using terahertz time-domain spectroscopy (THz-TDS) system at room temperature, their absorption spectra and the refractive spectra were obtained. Experimental results indicate that protein both has strong absorption but their characteristics were not distinct in the THz region, and the absorption decreased during thermal denatured state. In order to prove protein had been denatured, we used Differential scanning calorimeter (DSC) measured their denatured temperature, from their DSC heating traces, collagen Td=101℃, Bovine serum albumin Td=97℃. While we also combined the Fourier transform infrared spectrometer (FTIR) to investigate their secondary and tertiary structure before and after denatuation, but the results did not have the distinct changes. We turned the absorption spectra and the refractive spectra to the dielectric spectra, and used the one-stage Debye model simulated the terahertz dielectric spectra of protein before and after denaturation. This research proved that the terahertz spectrum technology is feasible in testing protein that were affected by temperature or other factors which can provide theoretical foundation in the further study about the THz spectrum of protein and peptide temperature stability.

  14. A Proposal for the Time Domain Modeling of Split Air Conditioners for Consumer Reimbursement Studies

    Science.gov (United States)

    Rezende, Paulo Henrique Oliveira; Almeida Junior, Afonso Bernardino; Gondim, Isaque Nogueira; Oliveira, José Carlos

    2015-04-01

    This paper deals with computer application procedures for the evaluation of the causal consistency between anomalous phenomena manifested in electrical networks, along with the physical damage associated with electrical equipment and possible reimbursement requests. The focus is on the development of an air conditioner appliance model of the type known as split founded upon a representation, in the time domain, in accordance with the Alternative Transients Program (ATP) simulator requirements. This approach permits investigations concerning the performance of the product when submitted to ideal and non-ideal supply conditions. Once the equipment model is implemented in the program, a set of investigative studies are carried out to show the device performance under specific energy quality disturbance conditions. In addition, there are still the results for the validation of the process established through the correlation between computational performance of the air conditioner with corresponding studies carried out experimentally, which are presented herein. Moreover, once the effectiveness of the developed model is verified, it is implemented into the Requests for Reimbursement Software. Investigations related to the correlation between disturbances and the levels of thermal and dielectric tolerance are then performed aiming at illustrating the use of the research results for the reimbursement analyzes purposes.

  15. An exploratory study of heavy domain wall fermions on the lattice

    CERN Document Server

    Boyle, Peter; Marinkovic, Marina Krstic; Sanfilippo, Francesco; Spraggs, Matthew; Tsang, Justus Tobias

    2016-01-01

    We report on an exploratory study of domain wall fermions (DWF) as a lattice regularisation for heavy quarks. Within the framework of quenched QCD with the tree-level improved Symanzik gauge action we identify the DWF parameters which minimise discretisation effects. We find the corresponding effective 4$d$ overlap operator to be exponentially local, independent of the quark mass. We determine a maximum bare heavy quark mass of $am_h\\approx 0.4$, below which the approximate chiral symmetry and O(a)-improvement of DWF are sustained. This threshold appears to be largely independent of the lattice spacing. Based on these findings, we carried out a detailed scaling study for the heavy-strange meson dispersion relation and decay constant on four ensembles with lattice spacings in the range $2.0-5.7\\,\\mathrm{GeV}$. We observe very mild $a^2$ scaling towards the continuum limit. Our findings establish a sound basis for heavy DWF in dynamical simulations of lattice QCD with relevance to Standard Model phenomenology.

  16. Membrane Sculpting by F-BAR Domains Studied by Molecular Dynamics Simulations

    Science.gov (United States)

    Yu, Hang; Schulten, Klaus

    2013-01-01

    Interplay between cellular membranes and their peripheral proteins drives many processes in eukaryotic cells. Proteins of the Bin/Amphiphysin/Rvs (BAR) domain family, in particular, play a role in cellular morphogenesis, for example curving planar membranes into tubular membranes. However, it is still unclear how F-BAR domain proteins act on membranes. Electron microscopy revealed that, in vitro, F-BAR proteins form regular lattices on cylindrically deformed membrane surfaces. Using all-atom and coarse-grained (CG) molecular dynamics simulations, we show that such lattices, indeed, induce tubes of observed radii. A 250 ns all-atom simulation reveals that F-BAR domain curves membranes via the so-called scaffolding mechanism. Plasticity of the F-BAR domain permits conformational change in response to membrane interaction, via partial unwinding of the domains 3-helix bundle structure. A CG simulation covering more than 350 µs provides a dynamic picture of membrane tubulation by lattices of F-BAR domains. A series of CG simulations identified the optimal lattice type for membrane sculpting, which matches closely the lattices seen through cryo-electron microscopy. PMID:23382665

  17. Ischemic preconditioning negatively regulates plenty of SH3s-mixed lineage kinase 3-Rac1 complex and c-Jun N-terminal kinase 3 signaling via activation of Akt.

    Science.gov (United States)

    Zhang, Q-G; Han, D; Xu, J; Lv, Q; Wang, R; Yin, X-H; Xu, T-L; Zhang, G-Y

    2006-12-01

    Activation of Akt/protein kinase B has been recently reported to play an important role in ischemic tolerance. We here demonstrate that the decreased protein expression and phosphorylation of phosphatase and tensin homolog deleted from chromosome 10 (PTEN) underlie the increased Akt-Ser-473 phosphorylation in the hippocampal CA1 subfield in ischemic preconditioning (IPC). Co-immunoprecipitation analysis reveals that Akt physically interacts with Rac1, a small Rho family GTPase required for mixed lineage kinase 3 (MLK3) autophosphorylation, and both this interaction and Rac1-Ser-71 phosphorylation induced by Akt are promoted in preconditioned rats. In addition, we show that Akt activation results in the disassembly of the plenty of SH3s (POSH)-MLK3-Rac1 signaling complex and down-regulation of the activation of MLK3/c-Jun N-terminal kinase (JNK) pathway. Akt activation results in decreased serine phosphorylation of 14-3-3, a cytoplasmic anchor of Bax, and prevents ischemia-induced mitochondrial translocation of Bax, release of cytochrome c, and activation of caspase-3. The expression of Fas ligand is also decreased in the CA1 region. Akt activation protects against apoptotic neuronal death as shown in TUNEL staining following IPC. Intracerebral infusion of LY294002 before IPC reverses the increase in Akt phosphorylation and the decrease in JNK signaling activation, as well as the neuroprotective action of IPC. Our results suggest that activation of pro-apoptotic MLK3/JNK3 cascade can be suppressed through activating anti-apoptotic phosphoinositide 3-kinase/Akt pathway induced by a sublethal ischemic insult, which provides a functional link between Akt and the JNK family of stress-activated kinases in ischemic tolerance.

  18. Optimized bacterial expression and purification of the c-Src catalytic domain for solution NMR studies

    International Nuclear Information System (INIS)

    Piserchio, Andrea; Ghose, Ranajeet; Cowburn, David

    2009-01-01

    Progression of a host of human cancers is associated with elevated levels of expression and catalytic activity of the Src family of tyrosine kinases (SFKs), making them key therapeutic targets. Even with the availability of multiple crystal structures of active and inactive forms of the SFK catalytic domain (CD), a complete understanding of its catalytic regulation is unavailable. Also unavailable are atomic or near-atomic resolution information about their interactions, often weak or transient, with regulating phosphatases and downstream targets. Solution NMR, the biophysical method best suited to tackle this problem, was previously hindered by difficulties in bacterial expression and purification of sufficient quantities of soluble, properly folded protein for economically viable labeling with NMR-active isotopes. Through a choice of optimal constructs, co-expression with chaperones and optimization of the purification protocol, we have achieved the ability to bacterially produce large quantities of the isotopically-labeled CD of c-Src, the prototypical SFK, and of its activating Tyr-phosphorylated form. All constructs produce excellent spectra allowing solution NMR studies of this family in an efficient manner

  19. Information technology governance domains in hospitals: a case study in Iran.

    Science.gov (United States)

    Shahi, Mehraban; Sadoughi, Farahnaz; Ahmadi, Maryam

    2014-11-30

    IT governance is a set of organizational structures ensuring decision-making rights and responsibilities with regard to the organization's IT assets. This qualitative study was carried out to identify the IT governance domains in teaching hospitals affiliated to Iran University of Medical Sciences. There were 10 heads of IT departments and 10 hospital directors. Semi structured interviews used for data collection. To analyze the data content analysis was applied. All the interviewees (100%) believed that decisions upon hospital software needs could be made in a decentralized fashion by the IT department of the university. Most of the interviewees (90%) believed that there were policies for logistics and maintenance of networks, purchase and maintenance, standards and general policies in the direction of the policies of the ministry of health and medical education. About 80% of the interviewees believed that the current emphasis of the hospital's IT unit and the hospital management for outsourcing of services were in the format of specialized contracts and under supervision of the university Statistic and IT department. A hospital strategic committee is an official organizational group consisting of hospital executives, heads of IT and multiple functional areas and business units in a hospital. In this committee, "the head of hospital" acts as the director of IT activities and ensures that IT strategies are alignment with the hospital business strategies.

  20. Experiences of using the Theoretical Domains Framework across diverse clinical environments: a qualitative study

    Science.gov (United States)

    Phillips, Cameron J; Marshall, Andrea P; Chaves, Nadia J; Jankelowitz, Stacey K; Lin, Ivan B; Loy, Clement T; Rees, Gwyneth; Sakzewski, Leanne; Thomas, Susie; To, The-Phung; Wilkinson, Shelley A; Michie, Susan

    2015-01-01

    Background The Theoretical Domains Framework (TDF) is an integrative framework developed from a synthesis of psychological theories as a vehicle to help apply theoretical approaches to interventions aimed at behavior change. Purpose This study explores experiences of TDF use by professionals from multiple disciplines across diverse clinical settings. Methods Mixed methods were used to examine experiences, attitudes, and perspectives of health professionals in using the TDF in health care implementation projects. Individual interviews were conducted with ten health care professionals from six disciplines who used the TDF in implementation projects. Deductive content and thematic analysis were used. Results Three main themes and associated subthemes were identified including: 1) reasons for use of the TDF (increased confidence, broader perspective, and theoretical underpinnings); 2) challenges using the TDF (time and resources, operationalization of the TDF) and; 3) future use of the TDF. Conclusion The TDF provided a useful, flexible framework for a diverse group of health professionals working across different clinical settings for the assessment of barriers and targeting resources to influence behavior change for implementation projects. The development of practical tools and training or support is likely to aid the utility of TDF. PMID:25834455

  1. Numerical study of time domain analogy applied to noise prediction from rotating blades

    Science.gov (United States)

    Fedala, D.; Kouidri, S.; Rey, R.

    2009-04-01

    Aeroacoustic formulations in time domain are frequently used to model the aerodynamic sound of airfoils, the time data being more accessible. The formulation 1A developed by Farassat, an integral solution of the Ffowcs Williams and Hawkings equation, holds great interest because of its ability to handle surfaces in arbitrary motion. The aim of this work is to study the numerical sensitivity of this model to specified parameters used in the calculation. The numerical algorithms, spatial and time discretizations, and approximations used for far-field acoustic simulation are presented. An approach of quantifying of the numerical errors resulting from implementation of formulation 1A is carried out based on Isom's and Tam's test cases. A helicopter blade airfoil, as defined by Farassat to investigate Isom's case, is used in this work. According to Isom, the acoustic response of a dipole source with a constant aerodynamic load, ρ0c02, is equal to the thickness noise contribution. Discrepancies are observed when the two contributions are computed numerically. In this work, variations of these errors, which depend on the temporal resolution, Mach number, source-observer distance, and interpolation algorithm type, are investigated. The results show that the spline interpolating algorithm gives the minimum error. The analysis is then extended to Tam's test case. Tam's test case has the advantage of providing an analytical solution for the first harmonic of the noise produced by a specific force distribution.

  2. Experiences of using the Theoretical Domains Framework across diverse clinical environments: a qualitative study.

    Science.gov (United States)

    Phillips, Cameron J; Marshall, Andrea P; Chaves, Nadia J; Jankelowitz, Stacey K; Lin, Ivan B; Loy, Clement T; Rees, Gwyneth; Sakzewski, Leanne; Thomas, Susie; To, The-Phung; Wilkinson, Shelley A; Michie, Susan

    2015-01-01

    The Theoretical Domains Framework (TDF) is an integrative framework developed from a synthesis of psychological theories as a vehicle to help apply theoretical approaches to interventions aimed at behavior change. This study explores experiences of TDF use by professionals from multiple disciplines across diverse clinical settings. Mixed methods were used to examine experiences, attitudes, and perspectives of health professionals in using the TDF in health care implementation projects. Individual interviews were conducted with ten health care professionals from six disciplines who used the TDF in implementation projects. Deductive content and thematic analysis were used. Three main themes and associated subthemes were identified including: 1) reasons for use of the TDF (increased confidence, broader perspective, and theoretical underpinnings); 2) challenges using the TDF (time and resources, operationalization of the TDF) and; 3) future use of the TDF. The TDF provided a useful, flexible framework for a diverse group of health professionals working across different clinical settings for the assessment of barriers and targeting resources to influence behavior change for implementation projects. The development of practical tools and training or support is likely to aid the utility of TDF.

  3. General Intelligence, Emotional Intelligence and Academic Knowledge as Predictors of Creativity Domains: A Study of Gifted Students

    Science.gov (United States)

    Sahin, Feyzullah

    2016-01-01

    Creativity of the individual is dependent on numerous factors, such as knowledge, general intelligence and emotional intelligence. The general purpose of this study is to investigate the effect of general intelligence, emotional intelligence and academic knowledge on the emerging of domain-specific creativity. The study was conducted on 178…

  4. A study of the border between the domains of production and acquisition of knowledge in higher education

    DEFF Research Database (Denmark)

    Busch, Henrik

    2001-01-01

    This paper focuses on a common feature of most undergraduate studies in science - the pronounced border between the domains of production and acquisition of knowledge. Under¬graduate students' learning activities and settings are characterized by little inter¬action with the community of practicing...... scientists. Based on ongoing ethnographic field work, certain aspects of this division between the two domains are discussed from an educational point of view. A case study is presented and leads to considerations about undergraduate students' access to the culture of practicing physicists....

  5. Crystallization and preliminary crystallographic studies of the C-terminal domain of outer membrane protein A from enterohaemorrhagic Escherichia coli

    International Nuclear Information System (INIS)

    Gu, Jiang; Ji, Xiaowei; Qi, Jianxun; Ma, Ying; Mao, Xuhu; Zou, Quanming

    2010-01-01

    In this study, recombinant OmpAC from EHEC was purified and crystallized and a diffraction data set was collected to 2.7 Å resolution. Outer membrane protein A (OmpA) of enterohaemorrhagic Escherichia coli (EHEC) plays multiple roles in bacterial physiology and pathogenesis, such as mediation of bacterial conjunction, maintenance of cell shape, induction of adhesion of EHEC to host cells etc. Better understanding of the functions of OmpA will help in the control of EHEC infections. OmpA is composed of two domains: the N-terminal domain and the C-terminal domain. The N-terminal domain is a β-barrel structure and embeds in the outer membrane of the bacterium. The structure and function of the C-terminal domain of OmpA (OmpAC) remain elusive. In this study, recombinant OmpAC from EHEC was purified and crystallized and a diffraction data set was collected to 2.7 Å resolution. The crystals belonged to space group I4 1 32, with unit-cell parameter a = 158.99 Å. The Matthews coefficient and solvent content were calculated to be 2.55 Å 3 Da −1 and 51.77%, respectively, for two molecules in the asymmetric unit

  6. Factors that influence effective perioperative temperature management by anesthesiologists: a qualitative study using the Theoretical Domains Framework.

    Science.gov (United States)

    Boet, Sylvain; Patey, Andrea M; Baron, Justine S; Mohamed, Karim; Pigford, Ashlee-Ann E; Bryson, Gregory L; Brehaut, Jamie C; Grimshaw, Jeremy M

    2017-06-01

    Inadvertent perioperative hypothermia (IPH) is associated with a range of adverse outcomes. Safe and effective warming techniques exist to prevent IPH; however, IPH remains common. This study aimed to identify factors that anesthesiologists perceive may influence temperature management during the perioperative period. After Research Ethics Board approval, semi-structured interviews were conducted with staff anesthesiologists at a Canadian academic hospital. An interview guide based on the Theoretical Domains Framework (TDF) was used to capture 14 theoretical domains that may influence temperature management. The interview transcripts were coded using direct content analysis to generate specific beliefs and to identify relevant TDF domains perceived to influence temperature management behaviour. Data saturation was achieved after 15 interviews. The following nine theoretical domains were identified as relevant to designing an intervention for practices in perioperative temperature management: knowledge, beliefs about capabilities, beliefs about consequences, reinforcement, memory/attention/decision-making, environmental context and resources, social/professional role/identity, social influences, and behavioural regulation. Potential target areas to improve temperature management practices include interventions that address information needs about individual temperature management behaviour as well as patient outcome (feedback), increasing awareness of possible temperature management strategies and guidelines, and a range of equipment and surgical team dynamics that influence temperature management. This study identified several potential target areas for future interventions from nine of the TDF behavioural domains that anesthesiologists perceive to drive their temperature management practices. Future interventions that aim to close the evidence-practice gap in perioperative temperature management may include these targets.

  7. STUDY REGARDING OVER BORDERS TOURISM AND ENTREPRENEURSHIP CULTURE IN THE DOMAIN

    Directory of Open Access Journals (Sweden)

    Andreş Solomia

    2012-06-01

    Full Text Available The study was regarded as a qualitative research that measures entrepreneurship tendencies of the two regions from the border rural environment, initiation and management measures of business in the rural environment. The study regarding entrepreneurship education knowledge of target member groups from the partner border communities from Caras-Severin and Serbia has as main objective the evaluating of entrepreneurship knowledge of communities from the two regions of the rural environment, both with a strong touristic and cultural potential, for the purpose of rebirth of border socio-economical activities and the improvement of life quality by developing rural tourism. The objective desired from this study were: a quantitative and qualitative of information level gained by the members of the target groups regarding the initiation and development of business in tourism; the establishing of an entrepreneur profile for the respondents; the identification of the activity domain with a high potential of economical exploitation. Starting from the premises that only a correct evaluation and a detailed information of these aspects will determine the fact that the results of the research will represent the basis of the elaborati2ng of a development strategy for the rural tourism for the border rural communities, the research team, to which I was also a member of, has used the method of investigation and questionnaires as useful instruments in the development of the activities of the Centre for Border Rural Tourism. These instruments have contributed to the knowledge and measuring of present dimensions from the two dimensions, qualitative and quantitative, of the level of basic entrepreneurship knowledge in order to stimulate in the future the inhabitants’ involvment in the development of tourism activities and of economical-social ones.

  8. Quantifying information transfer by protein domains: Analysis of the Fyn SH2 domain structure

    Directory of Open Access Journals (Sweden)

    Serrano Luis

    2008-10-01

    Full Text Available Abstract Background Efficient communication between distant sites within a protein is essential for cooperative biological response. Although often associated with large allosteric movements, more subtle changes in protein dynamics can also induce long-range correlations. However, an appropriate formalism that directly relates protein structural dynamics to information exchange between functional sites is still lacking. Results Here we introduce a method to analyze protein dynamics within the framework of information theory and show that signal transduction within proteins can be considered as a particular instance of communication over a noisy channel. In particular, we analyze the conformational correlations between protein residues and apply the concept of mutual information to quantify information exchange. Mapping out changes of mutual information on the protein structure then allows visualizing how distal communication is achieved. We illustrate the approach by analyzing information transfer by the SH2 domain of Fyn tyrosine kinase, obtained from Monte Carlo dynamics simulations. Our analysis reveals that the Fyn SH2 domain forms a noisy communication channel that couples residues located in the phosphopeptide and specificity binding sites and a number of residues at the other side of the domain near the linkers that connect the SH2 domain to the SH3 and kinase domains. We find that for this particular domain, communication is affected by a series of contiguous residues that connect distal sites by crossing the core of the SH2 domain. Conclusion As a result, our method provides a means to directly map the exchange of biological information on the structure of protein domains, making it clear how binding triggers conformational changes in the protein structure. As such it provides a structural road, next to the existing attempts at sequence level, to predict long-range interactions within protein structures.

  9. The PH domain of phosphoinositide-dependent kinase-1 exhibits a novel, phospho-regulated monomer-dimer equilibrium with important implications for kinase domain activation: single-molecule and ensemble studies.

    Science.gov (United States)

    Ziemba, Brian P; Pilling, Carissa; Calleja, Véronique; Larijani, Banafshé; Falke, Joseph J

    2013-07-16

    Phosphoinositide-dependent kinase-1 (PDK1) is an essential master kinase recruited to the plasma membrane by the binding of its C-terminal PH domain to the signaling lipid phosphatidylinositol-3,4,5-trisphosphate (PIP3). Membrane binding leads to PDK1 phospho-activation, but despite the central role of PDK1 in signaling and cancer biology, this activation mechanism remains poorly understood. PDK1 has been shown to exist as a dimer in cells, and one crystal structure of its isolated PH domain exhibits a putative dimer interface. It has been proposed that phosphorylation of PH domain residue T513 (or the phospho-mimetic T513E mutation) may regulate a novel PH domain dimer-monomer equilibrium, thereby converting an inactive PDK1 dimer to an active monomer. However, the oligomeric states of the PH domain on the membrane have not yet been determined, nor whether a negative charge at position 513 is sufficient to regulate its oligomeric state. This study investigates the binding of purified wild-type (WT) and T513E PDK1 PH domains to lipid bilayers containing the PIP3 target lipid, using both single-molecule and ensemble measurements. Single-molecule analysis of the brightness of the fluorescent PH domain shows that the PIP3-bound WT PH domain on membranes is predominantly dimeric while the PIP3-bound T513E PH domain is monomeric, demonstrating that negative charge at the T513 position is sufficient to dissociate the PH domain dimer and is thus likely to play a central role in PDK1 monomerization and activation. Single-molecule analysis of two-dimensional (2D) diffusion of PH domain-PIP3 complexes reveals that the dimeric WT PH domain diffuses at the same rate as a single lipid molecule, indicating that only one of its two PIP3 binding sites is occupied and there is little penetration of the protein into the bilayer as observed for other PH domains. The 2D diffusion of T513E PH domain is slower, suggesting the negative charge disrupts local structure in a way that allows

  10. Study on the coherence degree of magnetization reversal in Permalloy single-domain nano-ellipses

    Energy Technology Data Exchange (ETDEWEB)

    Júnior, D.S. Vieira [Departamento Acadêmico de Matemática, Física, e Estatística, Instituto Federal de Educação, Ciência e Tecnologia do Sudeste de Minas Gerais – Campus Rio Pomba, Rio Pomba, Minas Gerais 36180-000 (Brazil); Leonel, S.A. [Departamento de Física, Laboratório de Simulação Computacional, Universidade Federal de Juiz de Fora, Juiz de Fora, Minas Gerais 36036-330 (Brazil); Toscano, D., E-mail: danilotoscano@fisica.ufjf.br [Departamento de Física, Laboratório de Simulação Computacional, Universidade Federal de Juiz de Fora, Juiz de Fora, Minas Gerais 36036-330 (Brazil); Sato, F.; Coura, P.Z.; Dias, R.A. [Departamento de Física, Laboratório de Simulação Computacional, Universidade Federal de Juiz de Fora, Juiz de Fora, Minas Gerais 36036-330 (Brazil)

    2017-03-15

    Numerical simulations have been performed to study the magnetization reversal in Permalloy nano-ellipses, under combined in-plane magnetic fields along the longitudinal and the transverse directions. We have considered nano-ellipses with two different aspect ratios and five thicknesses: 220×80×t nm{sup 3} and 70×50×t nm{sup 3}, where t ranging from 5 to 25 nm in steps of 5 nm. We found that the mechanism of magnetization reversal is not only dependent on the parameters of the magnetic field pulse but also related to the ellipse dimensions. It is known that the reversal time is related to the mechanism behind the magnetization reversal. In particular, ultrafast magnetization reversals occur by coherent rotation, when applying a field oriented mainly perpendicular to the initial magnetization. In order to evaluate the degree of coherence of the magnetization reversal we have introduced a quantity called “coherence index”. Besides complementing the previous studies by including the effect of the thickness on the magnetization reversal, our results indicate that it is possible to obtain magnetization reversals with high degree of coherence in small nano-ellipses by adjusting the geometric factors of the ellipse and the parameters of the magnetic field pulse simultaneously. - Highlights: • Magnetization reversals in single-domain nano-ellipses were investigated. • A parameter to evaluate the degree of coherence of the magnetization reversal was proposed. • A higher coherence index indicates a complete, coherent, rotation of the magnetization.

  11. Systematic study of terahertz time-domain spectra of historically informed black inks.

    Science.gov (United States)

    Bardon, Tiphaine; May, Robert K; Taday, Philip F; Strlič, Matija

    2013-09-07

    The potential of terahertz-time domain spectroscopy (THz-TDS) as a diagnostic tool for studies of inks in historical documents is investigated in this paper. Transmission mode THz-TDS was performed on historically informed model writing and drawing inks. Carbon black, bistre and sepia inks show featureless spectra between 5 and 75 cm(-1) (0.15-2.25 THz); however, their analysis still provided useful information on the interaction of terahertz radiation with amorphous materials. On the other hand, THz-TDS can be used to distinguish different iron gall inks with respect to the amount of iron(II) sulfate contained, as sharp spectral features are observed for inks containing different ratios of iron(II) sulfate to tannic or gallic acid. Additionally, copper sulfate was found to modify the structure of iron(II) precipitate. Furthermore, Principal Component Analysis (PCA) applied to THz-TDS spectra, highlights changes in iron gall inks during thermal degradation, during which a decrease in the sharp spectral bands associated with iron(II) sulfate is observed. ATR-FTIR spectroscopy combined with THz-TDS of dynamically heated ink samples indicate that this phenomenon is due to dehydration of iron(II) sulfate heptahydrate. While this research demonstrates the potential of THz-TDS to improve monitoring of the chemical state of historical documents, the outcomes go beyond the heritage field, as it also helps to develop the theoretical knowledge on interactions between terahertz radiation and matter, particularly in studies of long-range symmetry (polymorphism) in complex molecular structures and the role played by the surrounding matrix, and also indicates the potential of THz-TDS for the optimization of contrast in terahertz imaging.

  12. Mutations in actin used for structural studies partially disrupt β-thymosin/WH2 domains interaction.

    Science.gov (United States)

    Deville, Célia; Girard-Blanc, Christine; Assrir, Nadine; Nhiri, Naïma; Jacquet, Eric; Bontems, François; Renault, Louis; Petres, Stéphane; van Heijenoort, Carine

    2016-10-01

    Understanding the structural basis of actin cytoskeleton remodeling requires stabilization of actin monomers, oligomers, and filaments in complex with partner proteins, using various biochemical strategies. Here, we report a dramatic destabilization of the dynamic interaction with a model β-thymosin/WH2 domain induced by mutations in actin. This result underlines that mutant actins should be used with prudence to characterize interactions with intrinsically disordered partners as destabilization of dynamic interactions, although identifiable by NMR, may be invisible to other structural techniques. It also highlights how both β-thymosin/WH2 domains and actin tune local structure and dynamics in regulatory processes involving intrinsically disordered domains. © 2016 Federation of European Biochemical Societies.

  13. Enhanced spectral domain optical coherence tomography for pathological and functional studies

    Science.gov (United States)

    Yuan, Zhijia

    Optical coherence tomography (OCT) is a novel technique that enables noninvasive or minimally invasive, cross-sectional imaging of biological tissue at sub-10mum spatial resolution and up to 2-3mm imaging depth. Numerous technological advances have emerged in recent years that have shown great potential to develop OCT into a powerful imaging and diagnostic tools. In particular, the implementation of Fourier-domain OCT (FDOCT) is a major step forward that leads to greatly improved imaging rate and image fidelity of OCT. This dissertation summarizes the work that focuses on enhancing the performances and functionalities of spectral radar based FDOCT (SDOCT) for pathological and functional applications. More specifically, chapters 1-4 emphasize on the development of SDOCT and its utility in pathological studies, including cancer diagnosis. The principle of SDOCT is first briefly outlined, followed by the design of our bench-top SDOCT systems with emphasis on spectral linear interpolation, calibration and system dispersion compensation. For ultrahigh-resolution SDOCT, time-lapse image registration and frame averaging is introduced to effectively reduce speckle noise and uncover subcellular details, showing great promise for enhancing the diagnosis of carcinoma in situ. To overcome the image depth limitation of OCT, a dual-modal imaging method combing SDOCT with high-frequency ultrasound is proposed and examined in animal cancer models to enhance the sensitivity and staging capabilities for bladder cancer diagnosis. Chapters 5-7 summarize the work on developing Doppler SDOCT for functional studies. Digital-frequency-ramping OCT (DFR-OCT) is developed in the study, which has demonstrated the ability to significantly improve the signal-to-noise ratio and thus sensitivity for retrieving subsurface blood flow imaging. New DFR algorithms and imaging processing methods are discussed to further enhance cortical CBF imaging. Applications of DFR-OCT for brain functional studies

  14. Chandra X-ray Time-Domain Study of Alpha Centauri AB, Procyon, and their Environs

    Science.gov (United States)

    Ayres, Thomas R.

    2018-06-01

    For more than a decade, Chandra X-ray Observatory has been monitoring the central AB binary (G2V+K1V) of the α Centauri triple system with semi-annual pointings, using the High-Resolution Camera. This study has been extended in recent years to the mid-F subgiant, Procyon. The main objective is to follow the coronal (T~1MK) activity variations of the three stars, analogous to the Sun's 11-year sunspot cycle. Tentative periods of 20 yr and 8 yr have been deduced for α Cen A and B, respectively; but so far Procyon has shown only a slow, very modest decline in count rate, which could well reflect a slight instrumental degradation rather than intrinsic behavior. The negligible high-energy variability of Procyon sits in stark contrast to the dramatic factor of several to ten changes in the X-ray luminosities of α Cen AB and the Sun over their respective cycles. Further, although sunlike α Cen A has been observed by successive generations of X-ray observatories for nearly four decades, albeit sporadically, there are key gaps in the coverage that affect the determination of the cycle period. In fact, the most recent pointings suggest a downturn in A's count rate that might be signaling a shorter, more solar-like cycle following a delayed minimum in the 2005--2010 time frame (perhaps an exaggerated version of the extended solar minimum between recent Cycles 23 and 24). Beyond the coronal cycles of the three stars, the sequence of periodic X-ray images represents a unique time-domain history concerning steady as well as variable sources in the two 30'x30' fields. The most conspicuous of the variable objects -- in the α Cen field -- will be described here.

  15. Identifying Domains of Ideas to Influence Early Childhood Teachers' Beliefs in Globalisation: A Mixed-Method Study

    Science.gov (United States)

    Tzuo, Pei-Wen; Tan, Liang See; Yang, Chien-Hui

    2013-01-01

    In the age of globalisation, it has been understood that teachers' beliefs revolve between old--new and local--foreign ideas of teaching and learning. The purpose of this study is to identify the domains of the various ideas that influence teachers' beliefs in globalisation, compare them to the strengths of influence, and explore the meanings of…

  16. Single-Domain Antibodies as Tools to Perturb and Study RNA Viruses

    NARCIS (Netherlands)

    Hanke, Leo

    2017-01-01

    In this thesis, I describe the generation and characterization of alpaca-derived, antiviral, single-domain antibody fragments (VHHs). The antiviral targets of the described VHHs are the nuclear proteins of influenza A virus (IAV) and vesicular stomatitis virus (VSV). The described VHHs protect cells

  17. Refined study of the interaction between HIV-1 p6 late domain and ALIX

    Directory of Open Access Journals (Sweden)

    Gerlier Denis

    2008-05-01

    Full Text Available Abstract The interaction between the HIV-1 p6 late budding domain and ALIX, a class E vacuolar protein sorting factor, was explored by using the yeast two-hybrid approach. We refined the ALIX binding site of p6 as being the leucine triplet repeat sequence (Lxx4 (LYPLTSLRSLFG. Intriguingly, the deletion of the C-terminal proline-rich region of ALIX prevented detectable binding to p6. In contrast, a four-amino acid deletion in the central hinge region of p6 increased its association with ALIX as shown by its ability to bind to ALIX lacking the proline rich domain. Finally, by using a random screening approach, the minimal ALIX391–510 fragment was found to specifically interact with this p6 deletion mutant. A parallel analysis of ALIX binding to the late domain p9 from EIAV revealed that p6 and p9, which exhibit distinct ALIX binding motives, likely bind differently to ALIX. Altogether, our data support a model where the C-terminal proline-rich domain of ALIX allows the access of its binding site to p6 by alleviating a conformational constraint resulting from the presence of the central p6 hinge.

  18. Study of stratified dielectric slab medium structures using pseudo-spectral time domain (PSTD) algorithm

    DEFF Research Database (Denmark)

    Tong, M.S.; Lu, Y.; Chen, Y.

    2005-01-01

    -layer structures are analyzed. Results show that this method matches satisfactorily the Nyquist sampling theorem in terms of spatial discretization. By comparing the given results, it is found that the PSTD method outperforms the finite-difference time-domain (FDTD) method in general, especially in terms...

  19. Exact diagonalization study of domain structures in integer filling factor quantum Hall ferromagnets

    Czech Academy of Sciences Publication Activity Database

    Rezayi, E. H.; Jungwirth, Tomáš; MacDonald, A. H.; Haldane, F. D. M.

    2003-01-01

    Roč. 67, č. 20 (2003), s. 201305-1 - 201305-4 ISSN 0163-1829 R&D Projects: GA ČR GA202/01/0754 Institutional research plan: CEZ:AV0Z1010914 Keywords : domain structure * integer filling factor * quantum Hall ferromagnets Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 2.962, year: 2003

  20. Experiences of using the Theoretical Domains Framework across diverse clinical environments: a qualitative study

    Directory of Open Access Journals (Sweden)

    Phillips CJ

    2015-03-01

    Framework (TDF is an integrative framework developed from a synthesis of psychological theories as a vehicle to help apply theoretical approaches to interventions aimed at behavior change. Purpose: This study explores experiences of TDF use by professionals from multiple disciplines across diverse clinical settings. Methods: Mixed methods were used to examine experiences, attitudes, and perspectives of health professionals in using the TDF in health care implementation projects. Individual interviews were conducted with ten health care professionals from six disciplines who used the TDF in implementation projects. Deductive content and thematic analysis were used. Results: Three main themes and associated subthemes were identified including: 1 reasons for use of the TDF (increased confidence, broader perspective, and theoretical underpinnings; 2 challenges using the TDF (time and resources, operationalization of the TDF and; 3 future use of the TDF. Conclusion: The TDF provided a useful, flexible framework for a diverse group of health professionals working across different clinical settings for the assessment of barriers and targeting resources to influence behavior change for implementation projects. The development of practical tools and training or support is likely to aid the utility of TDF. Keywords: barriers and enablers, behavioral change, evidence-based practice, implementation, health care, Theoretical Domains Framework

  1. Brazilian adults' sedentary behaviors by life domain: population-based study.

    Science.gov (United States)

    Mielke, Grégore I; da Silva, Inácio C M; Owen, Neville; Hallal, Pedro C

    2014-01-01

    There is rapidly-emerging evidence on the harmful health effects of sedentary behaviors. The aim of this paper was to quantify time in sedentary behaviors and document socio-demographic variations in different life domains among adults. A population-based survey was carried out in 2012 through face-to-face interviews with Brazilian adults aged 20+ years (N = 2,927). Information about time spent sedentary in a typical weekday was collected for five different domains (workplace, commuting, school/university, watching TV, and computer use at home). Descriptive and bivariate analyses examined variations in overall and domain-specific sedentary time by gender, age, educational attainment and socioeconomic position. On average, participants reported spending 5.8 (SD 4.5) hours per day sitting. The median value was 4.5 (interquartile range: 2.5-8) hours. Men, younger adults, those with higher schooling and from the wealthiest socioeconomic groups had higher overall sedentary scores. TV time was higher in women, older adults and among those with low schooling and socioeconomic position. Sedentary time in transport was higher in men, younger adults, and participants with high schooling and high socioeconomic position. Computer use at home was more frequent among young adults and those from high socioeconomic groups. Sitting at work was higher in those with higher schooling and from the wealthiest socioeconomic groups. Sedentary behavior at school was related inversely to age and directly to schooling. Patterns of sedentary behavior are different by life domains. Initiatives to reduce prolonged sitting among Brazilian adults will be required on multiple levels for different life domains.

  2. Brazilian adults' sedentary behaviors by life domain: population-based study.

    Directory of Open Access Journals (Sweden)

    Grégore I Mielke

    Full Text Available There is rapidly-emerging evidence on the harmful health effects of sedentary behaviors. The aim of this paper was to quantify time in sedentary behaviors and document socio-demographic variations in different life domains among adults.A population-based survey was carried out in 2012 through face-to-face interviews with Brazilian adults aged 20+ years (N = 2,927. Information about time spent sedentary in a typical weekday was collected for five different domains (workplace, commuting, school/university, watching TV, and computer use at home. Descriptive and bivariate analyses examined variations in overall and domain-specific sedentary time by gender, age, educational attainment and socioeconomic position.On average, participants reported spending 5.8 (SD 4.5 hours per day sitting. The median value was 4.5 (interquartile range: 2.5-8 hours. Men, younger adults, those with higher schooling and from the wealthiest socioeconomic groups had higher overall sedentary scores. TV time was higher in women, older adults and among those with low schooling and socioeconomic position. Sedentary time in transport was higher in men, younger adults, and participants with high schooling and high socioeconomic position. Computer use at home was more frequent among young adults and those from high socioeconomic groups. Sitting at work was higher in those with higher schooling and from the wealthiest socioeconomic groups. Sedentary behavior at school was related inversely to age and directly to schooling.Patterns of sedentary behavior are different by life domains. Initiatives to reduce prolonged sitting among Brazilian adults will be required on multiple levels for different life domains.

  3. Spectroscopic study of Alzheimer's amyloid fibrils using terahertz time domain spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Euna; Kim, Jeonghoi; Han, Younho; Moon, Kiwon; Lim, Meehyun; Han, Haewook; Park, Joonhyuck; Kim, Sungjee [POSTECH, Pohang (Korea, Republic of)

    2008-11-15

    Alzheimer's disease, one of the most common neurodegenerative diseases, is characterized by extensive amyloid deposition. Amyloid deposits contain the abundant fibrils formed by amyloid β protein (Aβ). Because amyloid fibrils are associated with amyloid diseases, including Alzheimer's disease, type 2 diabetes, prion disease, Parkinson's disease, senile systemic amyloidosis and Huntington's disease, there has been considerable interest within the biomedical and biochemical research communities. In transmission electron microscopic (TEM)images, amyloid firils are 0.1∼10μm long and approximately 10nm wide. Amyloid fibrils commonly exhibit self assembled filaments, often described as twisted or parallel assemblies of finer protofilaments. They are formed by the spontaneous aggregation of a wide variety of peptides and proteins. Structural studies of amyloid fibrils have revealed that the common structural motif of virtually all amyloid fibrils consists of cross β sheets in which the peptide strands are arranged perpendicular to the long axis of the fiber. But little was known until recently about the molecular level structures of amyloid fibils. Therefore, spectroscopic investigation of both amyloid fibrils and Aβ at the molecular level can provide the significant evidence for the molecular understanding of amyloidogenesis and for the development of innovative therapeutic and diagnostic approaches. We used terahertz time domain spectroscopy (THz TDS)to investigate both Aβ and amyloid fibril. THz TDS, developed over the last two decades, is a powerful tool to extract the properties of biomaterials and provides unique spectral signatures of biomolecules within 0.1∼10THz, which exists between microwave and infrared frequency range. Current interest in THz radiation arises from its capability of probing the delocalized collective vibrational modes in proteins. Studying the collective modes of proteins in THz frequency range can play an

  4. Nonlinear Optical Spectroscopy in the Time Domain: Studies of Ultrafast Molecular Processes in the Condensed Phase.

    Science.gov (United States)

    Joo, Taiha

    Ultrafast molecular processes in the condensed phase at room temperature are studied in the time domain by four wave mixing spectroscopy. The structure/dynamics of various quantum states can be studied by varying the time ordering of the incident fields, their polarization, their colors, etc. In one, time-resolved coherent Stokes Raman spectroscopy of benzene is investigated at room temperature. The reorientational correlation time of benzene as well as the T_2 time of the nu _1 ring-breathing mode have been measured by using two different polarization geometries. Bohr frequency difference beats have also been resolved between the nu_1 modes of ^ {12}C_6H_6 and ^{12}C_5^{13 }CH_6.. The dephasing dynamics of the nu _1 ring-breathing mode of neat benzene is studied by time-resolved coherent anti-Stokes Raman scattering. Ultrafast time resolution reveals deviation from the conventional exponential decay. The correlation time, tau _{rm c}, and the rms magnitude, Delta, of the Bohr frequency modulation are determined for the process responsible for the vibrational dephasing by Kubo dephasing function analysis. The electronic dephasing of two oxazine dyes in ethylene glycol at room temperature is investigated by photon echo experiments. It was found that at least two stochastic processes are responsible for the observed electronic dephasing. Both fast (homogeneous) and slow (inhomogeneous) dynamics are recovered using Kubo line shape analysis. Moreover, the slow dynamics is found to spectrally diffuse over the inhomogeneous distribution on the time scale around a picosecond. Time-resolved degenerate four wave mixing signal of dyes in a population measurement geometry is reported. The vibrational coherences both in the ground and excited electronic states produced strong oscillations in the signal together with the usual population decay from the excited electronic state. Absolute frequencies and their dephasing times of the vibrational modes at ~590 cm^{-1} are obtained

  5. Spectroscopic study of Alzheimer's amyloid fibrils using terahertz time domain spectroscopy

    International Nuclear Information System (INIS)

    Jung, Euna; Kim, Jeonghoi; Han, Younho; Moon, Kiwon; Lim, Meehyun; Han, Haewook; Park, Joonhyuck; Kim, Sungjee

    2008-01-01

    Alzheimer's disease, one of the most common neurodegenerative diseases, is characterized by extensive amyloid deposition. Amyloid deposits contain the abundant fibrils formed by amyloid β protein (Aβ). Because amyloid fibrils are associated with amyloid diseases, including Alzheimer's disease, type 2 diabetes, prion disease, Parkinson's disease, senile systemic amyloidosis and Huntington's disease, there has been considerable interest within the biomedical and biochemical research communities. In transmission electron microscopic (TEM)images, amyloid firils are 0.1∼10μm long and approximately 10nm wide. Amyloid fibrils commonly exhibit self assembled filaments, often described as twisted or parallel assemblies of finer protofilaments. They are formed by the spontaneous aggregation of a wide variety of peptides and proteins. Structural studies of amyloid fibrils have revealed that the common structural motif of virtually all amyloid fibrils consists of cross β sheets in which the peptide strands are arranged perpendicular to the long axis of the fiber. But little was known until recently about the molecular level structures of amyloid fibils. Therefore, spectroscopic investigation of both amyloid fibrils and Aβ at the molecular level can provide the significant evidence for the molecular understanding of amyloidogenesis and for the development of innovative therapeutic and diagnostic approaches. We used terahertz time domain spectroscopy (THz TDS)to investigate both Aβ and amyloid fibril. THz TDS, developed over the last two decades, is a powerful tool to extract the properties of biomaterials and provides unique spectral signatures of biomolecules within 0.1∼10THz, which exists between microwave and infrared frequency range. Current interest in THz radiation arises from its capability of probing the delocalized collective vibrational modes in proteins. Studying the collective modes of proteins in THz frequency range can play an important role in

  6. Study of magnetic domain evolution in an auxetic plane of Galfenol using Kerr microscopy

    Science.gov (United States)

    Raghunath, Ganesh; Flatau, Alison B.

    2015-05-01

    Galfenol (FexGa100-x), a magnetostrictive alloy (3/2λ 110-400 ppm) of Iron and Gallium exhibits an in-plane auxetic response in the ⟨110⟩ crystallographic direction. Negative Poisson's ratios have been observed in response to application of stress fields, where values of as low as -0.7 have been reported for compositions of greater than roughly 20% Ga [Zhang et al., J. Appl. Phys. 108(2), 023513 (2010)] and in response to application of magnetic fields, where values of as low as -2.5 have been reported to be expected for compositions of less than roughly 20% Ga [G. Raghunath and A. B. Flatau, IEEE Trans. Magn. (in press)]. Several models have been proposed to understand these two distinct phenomena. Galfenol samples with less than 20% Ga also exhibit an unusual response to an increasing magnetic field applied along the ⟨110⟩ direction. The longitudinal strain which increases initially with applied field experiences a dip (until ˜10 mT) before increasing again to reach saturation. The transverse strain increases and reaches a maximum value (at the same field of ˜10 mT) and then drops from the maximum by 5%-10% as magnetic saturation is approached [G. Raghunath and A. B. Flatau, IEEE Trans. Magn. (in press)].This work deals with discussing the evolution of magnetic domains in a 16 at. % Ga single crystal Galfenol sample when subjected to magnetic fields in the ⟨110⟩ direction in the (100) plane. The magnetic domains on the surface of mechanically polished Galfenol samples were imaged using Magneto-Optic Kerr Effect microscopy. Simultaneously, the strains along the longitudinal and transverse ⟨110⟩ directions were recorded using a bi-directional strain gauge rosette mounted on the unpolished bottom surface of the planar samples. The energy from the applied magnetic field is expected to grow the ⟨110⟩ oriented domains at the expense of domains oriented along all other directions. But since the plane has an easy ⟨100⟩ axis, we expect the

  7. Theoretical study of optical properties of anti phase domains in GaP

    Energy Technology Data Exchange (ETDEWEB)

    Tea, E., E-mail: etea.contact@gmail.com [Institute of R and D on Photovoltaic Energy (IRDEP) (UMR 7174, EDF-CNRS-ENSCP), 6 Quai Watier BP 49, 78401 Chatou cedex (France); FOTON INSA-Rennes (UMR 6082 CNRS), Université Européenne de Bretagne, 20 Avenue des Buttes de Coësmes, 35708 Rennes (France); Vidal, J.; Laribi, S.; Guillemoles, J.-F. [Institute of R and D on Photovoltaic Energy (IRDEP) (UMR 7174, EDF-CNRS-ENSCP), 6 Quai Watier BP 49, 78401 Chatou cedex (France); Pedesseau, L.; Cornet, C.; Jancu, J.-M.; Even, J.; Durand, O. [FOTON INSA-Rennes (UMR 6082 CNRS), Université Européenne de Bretagne, 20 Avenue des Buttes de Coësmes, 35708 Rennes (France)

    2014-02-14

    III-V/Si heterostructures are currently investigated for silicon photonics and solar energy conversion. In particular, dilute nitride alloy GaAsPN grown on a GaP/Si platform exhibits lattice match with Si and an optimal band gap configuration for tandem solar cell devices. However, monolithic “coherent” growth of the GaP thin layer on Si suffers from the nucleation of extended structural defects, which can hamper device operation as well as the GaP/Si interface level and through their propagation inside the overall heterostructure. However, the effect of such structural defects on optical and transport properties is actually not well understood in details. In this letter, we investigate the anti phase domains defect (also called inversion domains) by means of ab initio calculations giving insights into the alteration of optical and transport properties of GaP due to the defective GaP/Si interface.

  8. Study of the mapping mechanism of ferroelectric domains with the scanning force microscope

    International Nuclear Information System (INIS)

    Jungk, T.

    2006-12-01

    The piezo-force microscopy (PFM) allows the mapping of ferroelectric domains until the nanometer range. In spite of its simple function principle it was hitherto not completely understood. In ordser to develop the PFM further to a quantitative analysis method its methodical aspects were analyzed. It was shown that the fundamental mapping mechanism is based on the inverse piezo-effect. Different artefacts to be found in the literature could therefore be reduced to a measurement background. Furthermore the influence of the electrode geometry was analyzed. The width of doamin walls was systematically measured and simulated with a mode, whereby a maximal resolution of 17 nm was reached. By the development of a correction procedure for the exact detection of the forces acting on the spring-beam the lateral signals measured on domain walls could by newly interpreted. So the ''Lateral Electrostatic Force Microscopy'' was developed

  9. Exploratory Study of Operational Approaches to Increase Narcotics Interdiction in the Maritime Domain

    Science.gov (United States)

    2012-06-08

    Maritime Domain. 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Wesley H. Hester, LCDR, USCG 5d. PROJECT...analyzing, understanding, and acting” ( Cardon and Leonard 2010, 8). The applicable boundaries for the current environment exist in time and...inhospitable locations to hide during the day. It is likely that this trend will continue until either U.S. assets are consistently granted permission

  10. Ferroelectric domain pattern in barium titanate single crystals studied by means of digital holographic microscopy

    Czech Academy of Sciences Publication Activity Database

    Mokrý, Pavel; Psota, Pavel; Steiger, Kateřina; Václavík, Jan; Doleček, Roman; Vápenka, David; Lédl, Vít

    2016-01-01

    Roč. 49, č. 25 (2016), č. článku 255307. ISSN 0022-3727 R&D Projects: GA ČR(CZ) GA14-32228S Institutional support: RVO:61389021 Keywords : ferroelectric domain patterns * electro-optical materials * digital holographic microscopy Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 2.588, year: 2016 http://iopscience.iop.org/article/10.1088/0022-3727/49/25/255307

  11. Building a patchwork - The yeast plasma membrane as model to study lateral domain formation.

    Science.gov (United States)

    Schuberth, Christian; Wedlich-Söldner, Roland

    2015-04-01

    The plasma membrane (PM) has to fulfill a wide range of biological functions including selective uptake of substances, signal transduction and modulation of cell polarity and cell shape. To allow efficient regulation of these processes many resident proteins and lipids of the PM are laterally segregated into different functional domains. A particularly striking example of lateral segregation has been described for the budding yeast PM, where integral membrane proteins as well as lipids exhibit very slow translational mobility and form a patchwork of many overlapping micron-sized domains. Here we discuss the molecular and physical mechanisms contributing to the formation of a multi-domain membrane and review our current understanding of yeast PM organization. Many of the fundamental principles underlying membrane self-assembly and organization identified in yeast are expected to equally hold true in other organisms, even for the more transient and elusive organization of the PM in mammalian cells. This article is part of a Special Issue entitled: Nanoscale membrane organisation and signalling. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Study of two-dimensional transient cavity fields using the finite-difference time-domain technique

    International Nuclear Information System (INIS)

    Crisp, J.L.

    1988-06-01

    This work is intended to be a study into the application of the finite-difference time-domain, or FD-TD technique, to some of the problems faced by designers of equipment used in modern accelerators. In particular it discusses using the FD-TD algorithm to study the field distribution of a simple two-dimensional cavity in both space and time. 18 refs

  13. Study of two-dimensional transient cavity fields using the finite-difference time-domain technique

    Energy Technology Data Exchange (ETDEWEB)

    Crisp, J.L.

    1988-06-01

    This work is intended to be a study into the application of the finite-difference time-domain, or FD-TD technique, to some of the problems faced by designers of equipment used in modern accelerators. In particular it discusses using the FD-TD algorithm to study the field distribution of a simple two-dimensional cavity in both space and time. 18 refs.

  14. The study on mutations of the gene of extracellular domain of human thyrotropin receptor in the patients with thyroid diseases

    International Nuclear Information System (INIS)

    Zhang Zuncheng; Fang Peihua; Tan Jian; Lu Mei

    2002-01-01

    Objective: To define the sequence of the gene of extracellular domain of normal human thyrotropin receptor (hTSHR) and to investigate the mutations of the gene in the patients with thyroid diseases. Methods: Total RNAs were extracted from the thyroid tissue of four normal controls, twelve Graves' disease, four Hashimoto's thyroiditis and eleven nodular goiter patients. The extracellular domain of hTSHR genes were amplified by reverse transcription-polymerase chain reaction (RT-PCR) and sequenced with CEQ 2000 Genetic Analyzer. Results: The normal controls and the patients with thyroid disease had the same gene sequences of the extracellular domain of hTSHR. No mutation was found, except a silent base exchange in exon 7 (Asn187) at 661 base, in which 20 samples were 'T', 11 samples were 'C', without changes of amino acid of the TSHR. Conclusions: This study has not revealed mutations in the gene of extracellular domain of hTSHR. Other molecular pathogenetic mechanisms may be involved and more research is demanded

  15. Structure of lamellar lipid domains and corneocyte envelopes of murine stratum corneum. An X-ray diffraction study

    International Nuclear Information System (INIS)

    White, S.H.; Mirejovsky, D.; King, G.I.

    1988-01-01

    The lipid of the outermost layer of the skin is confined largely to the extracellular spaces surrounding the corneocytes of the stratum corneum where it forms a multilamellar adhesive matrix to act as the major permeability barrier of the skin. Knowledge of the molecular architecture of these intercellular domains is important for understanding various skin pathologies and their treatment, percutaneous drug delivery, and the cosmetic maintenance of the skin. The authors have surveyed by X-ray diffraction the structure of the intercellular domains and the extracted lipids of murine stratum corneum (SC) at 25, 45, and 70 0 C which are temperatures in the vicinity of known thermal phase transitions. The intercellular domains produce lamellar diffraction patterns with a Bragg spacing of 131 +/- 2 A. Lipid extracted from the SC and dispersed in excess water does not produce a simple lamellar diffraction pattern at any temperature studied, however. This and other facts suggest that another component, probably a protein, must be present to control the architecture of the intercellular lipid domains. They have also obtained diffraction patterns attributable to the protein envelopes of the corneocytes. The patterns suggest a β-pleated sheet organizational scheme. No diffraction patterns were observed that could be attributed to keratin

  16. Molecular Details of Olfactomedin Domains Provide Pathway to Structure-Function Studies.

    Directory of Open Access Journals (Sweden)

    Shannon E Hill

    Full Text Available Olfactomedin (OLF domains are found within extracellular, multidomain proteins in numerous tissues of multicellular organisms. Even though these proteins have been implicated in human disorders ranging from cancers to attention deficit disorder to glaucoma, little is known about their structure(s and function(s. Here we biophysically, biochemically, and structurally characterize OLF domains from H. sapiens olfactomedin-1 (npoh-OLF, also called noelin, pancortin, OLFM1, and hOlfA, and M. musculus gliomedin (glio-OLF, also called collomin, collmin, and CRG-L2, and compare them with available structures of myocilin (myoc-OLF recently reported by us and R. norvegicus glio-OLF and M. musculus latrophilin-3 (lat3-OLF by others. Although the five-bladed β-propeller architecture remains unchanged, numerous physicochemical characteristics differ among these OLF domains. First, npoh-OLF and glio-OLF exhibit prominent, yet distinct, positive surface charges and copurify with polynucleotides. Second, whereas npoh-OLF and myoc-OLF exhibit thermal stabilities typical of human proteins near 55°C, and most myoc-OLF variants are destabilized and highly prone to aggregation, glio-OLF is nearly 20°C more stable and significantly more resistant to chemical denaturation. Phylogenetically, glio-OLF is most similar to primitive OLFs, and structurally, glio-OLF is missing distinguishing features seen in OLFs such as the disulfide bond formed by N- and C- terminal cysteines, the sequestered Ca2+ ion within the propeller central hydrophilic cavity, and a key loop-stabilizing cation-π interaction on the top face of npoh-OLF and myoc-OLF. While deciphering the explicit biological functions, ligands, and binding partners for OLF domains will likely continue to be a challenging long-term experimental pursuit, we used structural insights gained here to generate a new antibody selective for myoc-OLF over npoh-OLF and glio-OLF as a first step in overcoming the impasse in

  17. Analisis Domain Proses COBIT Framework 5 Pada Sistem Informasi Worksheet (Studi Kasus: Perguruan Tinggi STMIK, Politeknik Palcomtech

    Directory of Open Access Journals (Sweden)

    Fahmi Ajismanto

    2018-01-01

    Full Text Available Perguruan tinggi Stmik, PalComTech adalah lembaga pendidikan komputer dan internet yang berdiri sejak tahun 2003. PalComTech menggunakan Sistem belajar praktek, diskusi, pemecahan studi kasus, praktikum di laboratorium dan setiap pertemuan didukung dengan fasilitas komputer dan internet. Sistem Pembelajaran Worksheet merupakan sistem informasi akademik yang digunakan oleh STMIK Palcomtech Palembang dalam kegiatan belajar mengajar. Penelitian ini menentukan domain proses pada Control Objectives for Information and Related Technology (COBIT 5 dan Analisa Current Maturity Level, pengukuran tingkat kematangan tata kelola Worksheet. Metode yang digunakan yaitu, deskriptif, quantitative dan metode analisis mengunakan COBIT 5. Berdasarkan hasil dari penelitian ini ditemukan bahwa proses domain COBIT Framework versi 5 yang digunakan adalah: (1. EDM, (Evaluate, Direct And Monitor, (a EDM03, (b EDM04 sedangkan pada domain  (2. APO (Align Plan and Organise yaitu: (a. APO02, (b. APO04, (c. APO07, (d. APO11, (e. APO12, (f. APO13 dan pada domain (3. MEA (Monitor Evaluate and Assess yaitu: MEA01. Hasil dari Analisis Current Maturity Level adalah: (1. EDM03 : 4,23 berada pada level 4 - Managed and Measureable,(2. APO12 : 4,15 berada pada level 4 - Managed and Measureable,   (3. APO07 : 4,07 berada pada level 4 - Managed and Measureable, (4. MEA01 Memantau,: 3,96 berada pada level 4 - Managed and Measureable, (5. EDM04: 3,90 berada pada level 4 - Managed and Measureable, (6. APO11: 3,80 berada pada level 4 - Managed and Measureable, (7. APO02: 3,70 berada pada level 4 -  Managed and Measureable, (8. APO13 : 3,61 berada pada level 4 - Managed and Measureable, (9. APO04: 3,55 berada pada level 4 - Managed and Measureable.   Keywords : COBIT Fremework 5, Tata Kelola TI, Domain Proses, Worksheet

  18. Time domain-nuclear magnetic resonance study of chars from southern hardwoods

    International Nuclear Information System (INIS)

    Elder, Thomas; Labbe, Nicole; Harper, David; Rials, Timothy

    2006-01-01

    Chars from the thermal degradation of silver maple (Acer saccharinum), red maple (Acer rubrum), sugar maple (Acer saccharum), and white oak (Quercus spp.), performed at temperatures from 250 to 350 o C, were examined using time domain-nuclear magnetic resonance spectroscopy. Prior to analysis, the chars were equilibrated under conditions insuring the presence of bound water only and both bound water and free water. Transverse relaxation times were found to be related to the moisture content of the chars, which varied with temperature. At elevated temperatures the number of signals assigned to free water decreased, indicative of an increase in pore size within the chars

  19. A life domains perspective on acculturation and psychological adjustment: a study of refugees from the former Soviet Union.

    Science.gov (United States)

    Birman, Dina; Simon, Corrina D; Chan, Wing Yi; Tran, Nellie

    2014-03-01

    The study articulates a contextual approach to research on acculturation of immigrants, suggesting that the relationship between acculturation and adjustment is dependent on the cultural demands of the life domains considered. Specifically, the study investigated the mediating effects of adjustment in occupational and social life domains on the relationship between acculturation and psychological adjustment for 391 refugees from the former Soviet Union. The study used bilinear measures of acculturation to the host (American) and heritage (Russian) cultures. Using Structural Equation Modeling, the study confirmed the hypothesized relationships, such that the positive effects of American acculturation on psychological adjustment were mediated by occupational adjustment, and the effects of Russian acculturation on psychological adjustment were mediated by satisfaction with co-ethnic social support. Psychological adjustment was measured in two ways, as psychological well-being, using a measure of life satisfaction, and as symptoms of depression and anxiety, using the Hopkins symptom checklist (HSCL). Life satisfaction served as a mediator between adjustment in occupational and social domains and HSCL, suggesting that it may be an intervening variable through which environmental stress associated with immigration contributes to the development of symptoms of mental disorder.

  20. Detergent/nanodisc screening for high-resolution NMR studies of an integral membrane protein containing a cytoplasmic domain.

    Directory of Open Access Journals (Sweden)

    Christos Tzitzilonis

    Full Text Available Because membrane proteins need to be extracted from their natural environment and reconstituted in artificial milieus for the 3D structure determination by X-ray crystallography or NMR, the search for membrane mimetic that conserve the native structure and functional activities remains challenging. We demonstrate here a detergent/nanodisc screening study by NMR of the bacterial α-helical membrane protein YgaP containing a cytoplasmic rhodanese domain. The analysis of 2D [(15N,(1H]-TROSY spectra shows that only a careful usage of low amounts of mixed detergents did not perturb the cytoplasmic domain while solubilizing in parallel the transmembrane segments with good spectral quality. In contrast, the incorporation of YgaP into nanodiscs appeared to be straightforward and yielded a surprisingly high quality [(15N,(1H]-TROSY spectrum opening an avenue for the structural studies of a helical membrane protein in a bilayer system by solution state NMR.

  1. Purification, crystallization and preliminary x-ray crystallographic studies of RAIDD Death-Domain (DD).

    Science.gov (United States)

    Jang, Tae-ho; Park, Hyun Ho

    2009-06-03

    Caspase-2 activation by formation of PIDDosome is critical for genotoxic stress induced apoptosis. PIDDosome is composed of three proteins, RAIDD, PIDD, and Caspase-2. RAIDD is an adaptor protein containing an N-terminal Caspase-Recruiting-Domain (CARD) and a C-terminal Death-Domain (DD). Its interactions with Caspase-2 and PIDD through CARD and DD respectively and formation of PIDDosome are important for the activation of Caspase-2. RAIDD DD cloned into pET26b vector was expressed in E. coli cells and purified by nickel affinity chromatography and gel filtration. Although it has been known that the most DDs are not soluble in physiological condition, RAIDD DD was soluble and interacts tightly with PIDD DD in physiological condition. The purified RAIDD DD alone has been crystallized. Crystals are trigonal and belong to space group P3(1)21 (or its enantiomorph P3(2)21) with unit-cell parameters a = 56.3, b = 56.3, c = 64.9 A and gamma = 120 degrees . The crystals were obtained at room temperature and diffracted to 2.0 A resolution.

  2. Purification, Crystallization and Preliminary X-ray Crystallographic Studies of RAIDD Death-Domain (DD

    Directory of Open Access Journals (Sweden)

    Hyun Ho Park

    2009-06-01

    Full Text Available Caspase-2 activation by formation of PIDDosome is critical for genotoxic stress induced apoptosis. PIDDosome is composed of three proteins, RAIDD, PIDD, and Caspase-2. RAIDD is an adaptor protein containing an N-terminal Caspase-Recruiting-Domain (CARD and a C-terminal Death-Domain (DD. Its interactions with Caspase-2 and PIDD through CARD and DD respectively and formation of PIDDosome are important for the activation of Caspase-2. RAIDD DD cloned into pET26b vector was expressed in E. coli cells and purified by nickel affinity chromatography and gel filtration. Although it has been known that the most DDs are not soluble in physiological condition, RAIDD DD was soluble and interacts tightly with PIDD DD in physiological condition. The purified RAIDD DD alone has been crystallized. Crystals are trigonal and belong to space group P3121 (or its enantiomorph P3221 with unit-cell parameters a = 56.3, b = 56.3, c = 64.9 Å and γ = 120°. The crystals were obtained at room temperature and diffracted to 2.0 Å resolution.

  3. Preliminary small-angle X-ray scattering and X-ray diffraction studies of the BTB domain of lola protein from Drosophila melanogaster

    Science.gov (United States)

    Boyko, K. M.; Nikolaeva, A. Yu.; Kachalova, G. S.; Bonchuk, A. N.; Dorovatovskii, P. V.; Popov, V. O.

    2017-11-01

    The Drosophila genome has several dozens of transcription factors (TTK group) containing BTB domains assembled into octamers. The LOLA protein belongs to this family. The purification, crystallization, and preliminary X-ray diffraction and small-angle X-ray scattering (SAXS) studies of the BTB domain of this protein are reported. The crystallization conditions were found by the vapor-diffusion technique. A very low diffraction resolution (8.7 Å resolution) of the crystals was insufficient for the determination of the threedimensional structure of the BTB domain. The SAXS study demonstrated that the BTB domain of the LOLA protein exists as an octamer in solution.

  4. Interaction of an anticancer peptide fragment of azurin with p53 and its isolated domains studied by atomic force spectroscopy.

    Science.gov (United States)

    Bizzarri, Anna Rita; Santini, Simona; Coppari, Emilia; Bucciantini, Monica; Di Agostino, Silvia; Yamada, Tohru; Beattie, Craig W; Cannistraro, Salvatore

    2011-01-01

    p28 is a 28-amino acid peptide fragment of the cupredoxin azurin derived from Pseudomonas aeruginosa that preferentially penetrates cancerous cells and arrests their proliferation in vitro and in vivo. Its antitumor activity reportedly arises from post-translational stabilization of the tumor suppressor p53 normally downregulated by the binding of several ubiquitin ligases. This would require p28 to specifically bind to p53 to inhibit specific ligases from initiating proteosome-mediated degradation. In this study, atomic force spectroscopy, a nanotechnological approach, was used to investigate the interaction of p28 with full-length p53 and its isolated domains at the single molecule level. Analysis of the unbinding forces and the dissociation rate constant suggest that p28 forms a stable complex with the DNA-binding domain of p53, inhibiting the binding of ubiquitin ligases other than Mdm2 to reduce proteasomal degradation of p53.

  5. [Expression, crystallization and crystallographic study of the 1st IgV domain of human CD96].

    Science.gov (United States)

    Jiang, Wenjing; Zhang, Shuijun; Yan, Jinghua; Guo, Ning

    2013-05-01

    CD96 (Tactile) is an adhesion receptor expressed mainly on activated T cells, NK cells. As a family member of the immunoglobulin-like cell receptor, CD96 consists of three immunoglobulin-like domains (V1, V2/C and C) in the extracellular region. Recent studies have shown that the 1st IgV domain of CD96 (CD96V1) plays an essential role in cell adhesion and NK cell-mediated killing. In this study, the 1st IgV domain of human CD96 (hCD96V1) was cloned and expressed in Escherichia coli (BL21). The soluble protein was obtained by refolding of the hCD96V1 inclusion bodies. From analytical ultracentrifugation, we could predict that CD96 V1 maily exists as dimer with approximate molecular weight of 26.9 kDa. The protein was then successfully crystallized using the sitting-drop vapour-diffusion method. The crystals diffracted to 1.9 angstrom resolution and belonged to space group P21, with unit-cell parameters a = 35.1, b = 69.5, c = 49.6A, alpha=gamma=90 degrees, beta=105.4 degrees.

  6. Where do bright ideas occur in our brain? Meta-analytic evidence from neuroimaging studies of domain-specific creativity

    Science.gov (United States)

    Boccia, Maddalena; Piccardi, Laura; Palermo, Liana; Nori, Raffaella; Palmiero, Massimiliano

    2015-01-01

    Many studies have assessed the neural underpinnings of creativity, failing to find a clear anatomical localization. We aimed to provide evidence for a multi-componential neural system for creativity. We applied a general activation likelihood estimation (ALE) meta-analysis to 45 fMRI studies. Three individual ALE analyses were performed to assess creativity in different cognitive domains (Musical, Verbal, and Visuo-spatial). The general ALE revealed that creativity relies on clusters of activations in the bilateral occipital, parietal, frontal, and temporal lobes. The individual ALE revealed different maximal activation in different domains. Musical creativity yields activations in the bilateral medial frontal gyrus, in the left cingulate gyrus, middle frontal gyrus, and inferior parietal lobule and in the right postcentral and fusiform gyri. Verbal creativity yields activations mainly located in the left hemisphere, in the prefrontal cortex, middle and superior temporal gyri, inferior parietal lobule, postcentral and supramarginal gyri, middle occipital gyrus, and insula. The right inferior frontal gyrus and the lingual gyrus were also activated. Visuo-spatial creativity activates the right middle and inferior frontal gyri, the bilateral thalamus and the left precentral gyrus. This evidence suggests that creativity relies on multi-componential neural networks and that different creativity domains depend on different brain regions. PMID:26322002

  7. Extended criteria and predictors in college admission: Exploring the structure of study success and investigating the validity of domain knowledge

    Directory of Open Access Journals (Sweden)

    OLGA KUNINA

    2007-06-01

    Full Text Available The utility of aptitude tests and intelligence measures in the prediction of the success in college is one of the empirically best supported results in ability research. However, the structure of the criterion “study success” has not been appropriately investigated so far. Moreover, it remains unclear which aspect of intelligence – fluid intelligence or crystallized intelligence – has the major impact on the prediction. In three studies we have investigated the dimensionality of the criterion achievements as well as the relative contributions of competing ability predictors. In the first study, the dimensionality of college grades was explored in a sample of 629 alumni. A measurement model with two correlated latent factors distinguishing undergraduate college grades on the one hand from graduate college grades on the other hand had the best fit to the data. In the second study, a group of 179 graduate students completed a Psychology knowledge test and provided available college grades in undergraduate studies. A model separating a general latent factor for Psychology knowledge from a nested method factor for college grades, and a second nested factor for “experimental orientation” had the best fit to the data. In the third study the predictive power of domain specific knowledge tests in Mathematics, English, and Biology was investigated. A sample of 387 undergraduate students in this prospective study additionally completed a compilation of fluid intelligence tests. The results of this study indicate as expected that: a ability measures are incrementally predictive over school grades in predicting exam grades; and b that knowledge tests from relevant domains were incrementally predictive over fluid intelligence. The results of these studies suggest that criteria for college admission tests deserve and warrant more attention, and that domain specific ability indicators can contribute to the predictive validity of established

  8. Far-infrared vibrational modes of DNA components studied by terahertz time-domain spectroscopy

    International Nuclear Information System (INIS)

    Fischer, B M; Walther, M; Jepsen, P Uhd

    2002-01-01

    The far-infrared dielectric function of a wide range of organic molecules is dominated by vibrations involving a substantial fraction of the atoms forming the molecule and motion associated with intermolecular hydrogen bond vibrations. Due to their collective nature such modes are highly sensitive to the intra- and intermolecular structure and thus provide a unique fingerprint of the conformational state of the molecule and effects of its environment. We demonstrate the use of terahertz time-domain spectroscopy (THz-TDS) for recording the far-infrared (0.5-4.0 THz) dielectric function of the four nucleobases and corresponding nucleosides forming the building blocks of deoxyribose nucleic acid (DNA). We observe numerous distinct spectral features with large differences between the molecules in both frequency-dependent absorption coefficient and index of refraction. Assisted by results from density-functional calculations we interpret the origin of the observed resonances as vibrations of hydrogen bonds between the molecules

  9. Conformational entropic maps of functional coupling domains in GPCR activation: A case study with beta2 adrenergic receptor

    Science.gov (United States)

    Liu, Fan; Abrol, Ravinder; Goddard, William, III; Dougherty, Dennis

    2014-03-01

    Entropic effect in GPCR activation is poorly understood. Based on the recent solved structures, researchers in the GPCR structural biology field have proposed several ``local activating switches'' that consisted of a few number of conserved residues, but have long ignored the collective dynamical effect (conformational entropy) of a domain comprised of an ensemble of residues. A new paradigm has been proposed recently that a GPCR can be viewed as a composition of several functional coupling domains, each of which undergoes order-to-disorder or disorder-to-order transitions upon activation. Here we identified and studied these functional coupling domains by comparing the local entropy changes of each residue between the inactive and active states of the β2 adrenergic receptor from computational simulation. We found that agonist and G-protein binding increases the heterogeneity of the entropy distribution in the receptor. This new activation paradigm and computational entropy analysis scheme provides novel ways to design functionally modified mutant and identify new allosteric sites for GPCRs. The authors thank NIH and Sanofi for funding this project.

  10. Dynamic trafficking of wheat γ-gliadin and of its structural domains in tobacco cells, studied with fluorescent protein fusions

    Science.gov (United States)

    Francin-Allami, Mathilde; Saumonneau, Amélie; Lavenant, Laurence; Bouder, Axelle; Sparkes, Imogen; Hawes, Chris; Popineau, Yves

    2011-01-01

    Prolamins, the main storage proteins of wheat seeds, are synthesized and retained in the endoplasmic reticulum (ER) of the endosperm cells, where they accumulate in protein bodies (PBs) and are then exported to the storage vacuole. The mechanisms leading to these events are unresolved. To investigate this unconventional trafficking pathway, wheat γ-gliadin and its isolated repeated N-terminal and cysteine-rich C-terminal domains were fused to fluorescent proteins and expressed in tobacco leaf epidermal cells. The results indicated that γ-gliadin and both isolated domains were able to be retained and accumulated as protein body-like structures (PBLS) in the ER, suggesting that tandem repeats are not the only sequence involved in γ-gliadin ER retention and PBLS formation. The high actin-dependent mobility of γ-gliadin PBLS is also reported, and it is demonstrated that most of them do not co-localize with Golgi body or pre-vacuolar compartment markers. Both γ-gliadin domains are found in the same PBLS when co-expressed, which is most probably due to their ability to interact with each other, as indicated by the yeast two-hybrid and FRET-FLIM experiments. Moreover, when stably expressed in BY-2 cells, green fluorescent protein (GFP) fusions to γ-gliadin and its isolated domains were retained in the ER for several days before being exported to the vacuole in a Golgi-dependent manner, and degraded, leading to the release of the GFP ‘core’. Taken together, the results show that tobacco cells are a convenient model to study the atypical wheat prolamin trafficking with fluorescent protein fusions. PMID:21617248

  11. Familiarity Vs Trust: A Comparative Study of Domain Scientists' Trust in Visual Analytics and Conventional Analysis Methods.

    Science.gov (United States)

    Dasgupta, Aritra; Lee, Joon-Yong; Wilson, Ryan; Lafrance, Robert A; Cramer, Nick; Cook, Kristin; Payne, Samuel

    2017-01-01

    Combining interactive visualization with automated analytical methods like statistics and data mining facilitates data-driven discovery. These visual analytic methods are beginning to be instantiated within mixed-initiative systems, where humans and machines collaboratively influence evidence-gathering and decision-making. But an open research question is that, when domain experts analyze their data, can they completely trust the outputs and operations on the machine-side? Visualization potentially leads to a transparent analysis process, but do domain experts always trust what they see? To address these questions, we present results from the design and evaluation of a mixed-initiative, visual analytics system for biologists, focusing on analyzing the relationships between familiarity of an analysis medium and domain experts' trust. We propose a trust-augmented design of the visual analytics system, that explicitly takes into account domain-specific tasks, conventions, and preferences. For evaluating the system, we present the results of a controlled user study with 34 biologists where we compare the variation of the level of trust across conventional and visual analytic mediums and explore the influence of familiarity and task complexity on trust. We find that despite being unfamiliar with a visual analytic medium, scientists seem to have an average level of trust that is comparable with the same in conventional analysis medium. In fact, for complex sense-making tasks, we find that the visual analytic system is able to inspire greater trust than other mediums. We summarize the implications of our findings with directions for future research on trustworthiness of visual analytic systems.

  12. Domain crossing

    DEFF Research Database (Denmark)

    Schraefel, M. C.; Rouncefield, Mark; Kellogg, Wendy

    2012-01-01

    In CSCW, how much do we need to know about another domain/culture before we observe, intersect and intervene with designs. What optimally would that other culture need to know about us? Is this a “how long is a piece of string” question, or an inquiry where we can consider a variety of contexts a...

  13. Insight into the adsorption profiles of the Saprolegnia monoica chitin synthase MIT domain on POPA and POPC membranes by molecular dynamics simulation studies.

    Science.gov (United States)

    Kuang, Guanglin; Liang, Lijun; Brown, Christian; Wang, Qi; Bulone, Vincent; Tu, Yaoquan

    2016-02-21

    The critical role of chitin synthases in oomycete hyphal tip growth has been established. A microtubule interacting and trafficking (MIT) domain was discovered in the chitin synthases of the oomycete model organism, Saprolegnia monoica. MIT domains have been identified in diverse proteins and may play a role in intracellular trafficking. The structure of the Saprolegnia monoica chitin synthase 1 (SmChs1) MIT domain has been recently determined by our group. However, although our in vitro assay identified increased strength in interactions between the MIT domain and phosphatidic acid (PA) relative to other phospholipids including phosphatidylcholine (PC), the mechanism used by the MIT domain remains unknown. In this work, the adsorption behavior of the SmChs1 MIT domain on POPA and POPC membranes was systematically investigated by molecular dynamics simulations. Our results indicate that the MIT domain can adsorb onto the tested membranes in varying orientations. Interestingly, due to the specific interactions between MIT residues and lipid molecules, the binding affinity to the POPA membrane is much higher than that to the POPC membrane. A binding hotspot, which is critical for the adsorption of the MIT domain onto the POPA membrane, was also identified. The lower binding affinity to the POPC membrane can be attributed to the self-saturated membrane surface, which is unfavorable for hydrogen-bond and electrostatic interactions. The present study provides insight into the adsorption profile of SmChs1 and additionally has the potential to improve our understanding of other proteins containing MIT domains.

  14. Study of time-domain digital pulse shaping algorithms for nuclear signals

    International Nuclear Information System (INIS)

    Zhou Jianbin; Tuo Xianguo; Zhu Xing; Liu Yi; Zhou Wei; Lei Jiarong

    2012-01-01

    With the development on high-speed integrated circuit, fast high resolution sampling ADC and digital signal processors are replacing analog shaping amplifier circuit. This paper firstly presents the numerical analysis and simulation on R-C shaping circuit model and C-R shaping circuit model. Mathematic models are established based on 1 st order digital differential method and Kirchhoff Current Law in time domain, and a simulation and error evaluation experiment on an ideal digital signal are carried out with Excel VBA. A digital shaping test for a semiconductor X-ray detector in real time is also presented. Then a numerical analysis for Sallen-Key(S-K) low-pass filter circuit model is implemented based on the analysis of digital R-C and digital C-R shaping methods. By applying the 2 nd order non-homogeneous differential equation,the authors implement a digital Gaussian filter model for a standard exponential-decaying signal and a nuclear pulse signal. Finally, computer simulations and experimental tests are carried out and the results show the possibility of the digital pulse processing algorithms. (authors)

  15. Comparative study of boson peak in normal and secondary alcohols with terahertz time-domain spectroscopy

    International Nuclear Information System (INIS)

    Yomogida, Yoshiki; Sato, Yuki; Nozaki, Ryusuke; Mishina, Tomobumi; Nakahara, Jun'ichiro

    2010-01-01

    Using terahertz (THz) time-domain spectroscopy, we measured the complex permittivity of some normal (1-propanol, 1-butanol, and 1-pentanol) and secondary alcohols (2-propanol, 2-butanol, and 2-pentanol) in the frequency ranges from 0.2 to 2.5 THz at temperatures from 253 to 323 K. For all the samples, the complex permittivity in the THz region includes the following three components: (i) a high frequency side of dielectric relaxation processes, (ii) a broad mode around 1 THz, and (iii) a low frequency side of an intermolecular vibration mode located above 2.5 THz. The mode around 1 THz is recognized as a boson peak which is related to the local structure of disordered materials. The intensity of the boson peak in secondary alcohols is higher than that in normal alcohols. On the other hand, the number of carbon atoms slightly affects the appearance of the boson peak. These observations indicate that the position of an OH group in a molecule has a profound effect on the local structures in monohydric alcohols.

  16. PTB domain-directed substrate targeting in a tyrosine kinase from the unicellular choanoflagellate Monosiga brevicollis.

    Directory of Open Access Journals (Sweden)

    Victoria Prieto-Echagüe

    2011-04-01

    Full Text Available Choanoflagellates are considered to be the closest living unicellular relatives of metazoans. The genome of the choanoflagellate Monosiga brevicollis contains a surprisingly high number and diversity of tyrosine kinases, tyrosine phosphatases, and phosphotyrosine-binding domains. Many of the tyrosine kinases possess combinations of domains that have not been observed in any multicellular organism. The role of these protein interaction domains in M. brevicollis kinase signaling is not clear. Here, we have carried out a biochemical characterization of Monosiga HMTK1, a protein containing a putative PTB domain linked to a tyrosine kinase catalytic domain. We cloned, expressed, and purified HMTK1, and we demonstrated that it possesses tyrosine kinase activity. We used immobilized peptide arrays to define a preferred ligand for the third PTB domain of HMTK1. Peptide sequences containing this ligand sequence are phosphorylated efficiently by recombinant HMTK1, suggesting that the PTB domain of HMTK1 has a role in substrate recognition analogous to the SH2 and SH3 domains of mammalian Src family kinases. We suggest that the substrate recruitment function of the noncatalytic domains of tyrosine kinases arose before their roles in autoinhibition.

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

    Directory of Open Access Journals (Sweden)

    Owens Raymond J

    2010-05-01

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

  18. Eclectic continuum, distinct discipline or sub-domain of communication studies? Theoretical considerations and empirical findings on the disciplinarity, multidisciplinarity and transdisciplinarity of journalism studies

    Directory of Open Access Journals (Sweden)

    Martin Löffelholz

    2011-06-01

    Full Text Available Is journalism studies a sub-domain of communication studies, adistinct discipline, a multidisciplinary merger or a transdisciplinary endeavour? This question is discussed by analyzing the 2008 and2009 volumes of seven academic journals focusing on journalismresearch. The sample includes 349 articles published in BrazilianJournalism Research, Ecquid Novi, Journalism & CommunicationMonographs, Journalism & Mass Communication Quarterly, PacificJournalism Review, Journalism Studies, or Journalism: Theory,Practice and Criticism. Overall, the findings reveal that journalismresearch mainly applies theoretical approaches and empiricalmethods deriving from other disciplines, particularly sociology, psychology or cultural studies. In many countries, however, journalism studies has reached a comparatively high level of institutionalization indicated by the large number of specific schools, professorships, professional associations and respective academic journals. In conclusion, we argue that journalism studies is a sub-domain of communication studies, which integrates andtranscends various disciplines aiming to become one of the axialsubjects of the 21st century.

  19. ECLECTIC CONTINUUM, DISTINCT DISCIPLINE OR SUB-DOMAIN OF COMMUNICATION STUDIES? Theoretical considerations and empirical findings on the disciplinarity, multidisciplinarity and transdisciplinarity of journalism studies

    Directory of Open Access Journals (Sweden)

    Liane Rothenberger

    2011-06-01

    Full Text Available Is journalism studies a sub-domain of communication studies, adistinct discipline, a multidisciplinary merger or a transdisciplinary endeavour? This question is discussed by analyzing the 2008 and2009 volumes of seven academic journals focusing on journalismresearch. The sample includes 349 articles published in BrazilianJournalism Research, Ecquid Novi, Journalism & CommunicationMonographs, Journalism & Mass Communication Quarterly, PacificJournalism Review, Journalism Studies, or Journalism: Theory,Practice and Criticism. Overall, the findings reveal that journalismresearch mainly applies theoretical approaches and empiricalmethods deriving from other disciplines, particularly sociology, psychology or cultural studies. In many countries, however, journalism studies has reached a comparatively high level of institutionalization indicated by the large number of specific schools, professorships, professional associations and respective academic journals. In conclusion, we argue that journalism studies is a sub-domain of communication studies, which integrates andtranscends various disciplines aiming to become one of the axialsubjects of the 21st century.

  20. Correlations between physical activity and neurocognitive domain functions in patients with schizophrenia: a cross-sectional study.

    Science.gov (United States)

    Kurebayashi, Yusuke; Otaki, Junichi

    2017-01-05

    Neurocognitive dysfunction is a critical target symptom of schizophrenia treatment. A positive correlation between physical activity level and neurocognitive function has been reported in healthy individuals, but it is unclear whether such a correlation exists in patients with schizophrenia and whether the relationship is different according to inpatients or outpatients. This study aimed to examine the differences in the correlations between physical activity and multiple neurocognitive domains in inpatients and outpatients with schizophrenia and obtain suggestions for further study to facilitate this field. Twenty-nine patients with schizophrenia were examined (16 inpatients and 13 outpatients, 56.0 ± 11.4 years of age). Current symptoms were assessed using the Positive and Negative Symptom Scale and neurocognitive functions using Cognitrax, which yields a composite neurocognitive index (NCI) and 11 domain scores. After testing, participants wore an HJA-750C accelerometer for one week to measure physical activity levels and durations. Partial correlation analyses were performed between exercise and cognitive parameters. In the outpatient group, higher physical activity was associated with faster Motor and Psychomotor Speeds in outpatients. However, higher physical activity was associated with lower overall NCI, Attention score, and Memory scores in inpatients. Although higher physical activity was associated with better neurocognitive functions of outpatients, in inpatients with non-remitted schizophrenia, higher physical activity was associated with worsening of several cognitive domains. In a future study examining the relationship between physical activity and neurocognitive function for facilitating this research field, separation between inpatients and outpatients are needed because the relationship is different between inpatients and outpatients.

  1. [Domains of physical activity in slave-descendant communities in Southwest Bahia State, Brazil: a population-based study].

    Science.gov (United States)

    Bezerra, Vanessa Moraes; Andrade, Amanda Cristina de Souza; César, Cibele Comini; Caiaffa, Waleska Teixeira

    2015-06-01

    This study aimed to describe the prevalence of physical activity (PA) and associated factors in various domains (leisure-time, work, home, and commuting) among quilombolas (descendants of African slaves) in Bahia State, Brazil. This was a cross-sectional study of 797 individuals from 18 to 100 years of age. The study adopted a cutoff point of 150 minutes of PA per week. A hierarchical Poisson model was used. The highest prevalence of PA was at work (42.1%), followed by the home environment (39.3%), commuting (35.5%), and leisure time (13.1%). PA at work was associated with male gender, lower age, higher schooling, and consumption of alcohol and fruits. PA in the household domain was associated with female gender, lower age, marital status (married), and negative self-rated health. In commuting, PA was associated with male gender and lower age bracket, and during leisure time with safety, male gender, lower age, and higher schooling. The study concludes that this slave-descendant community displays a profile of PA that is characteristic of rural groups (more active at work, with little leisure-time activity). The determinants of PA were similar to those seen in urban groups.

  2. Trusted Domain

    DEFF Research Database (Denmark)

    Hjorth, Theis Solberg; Torbensen, Rune

    2012-01-01

    remote access via IP-based devices such as smartphones. The Trusted Domain platform fits existing legacy technologies by managing their interoperability and access controls, and it seeks to avoid the security issues of relying on third-party servers outside the home. It is a distributed system...... of wireless standards, limited resources of embedded systems, etc. Taking these challenges into account, we present a Trusted Domain home automation platform, which dynamically and securely connects heterogeneous networks of Short-Range Wireless devices via simple non-expert user. interactions, and allows......In the digital age of home automation and with the proliferation of mobile Internet access, the intelligent home and its devices should be accessible at any time from anywhere. There are many challenges such as security, privacy, ease of configuration, incompatible legacy devices, a wealth...

  3. Computational Studies of the Active and Inactive Regulatory Domains of Response Regulator PhoP Using Molecular Dynamics Simulations.

    Science.gov (United States)

    Qing, Xiao-Yu; Steenackers, Hans; Venken, Tom; De Maeyer, Marc; Voet, Arnout

    2017-11-01

    The response regulator PhoP is part of the PhoP/PhoQ two-component system, which is responsible for regulating the expression of multiple genes involved in controlling virulence, biofilm formation, and resistance to antimicrobial peptides. Therefore, modulating the transcriptional function of the PhoP protein is a promising strategy for developing new antimicrobial agents. There is evidence suggesting that phosphorylation-mediated dimerization in the regulatory domain of PhoP is essential for its transcriptional function. Disruption or stabilization of protein-protein interactions at the dimerization interface may inhibit or enhance the expression of PhoP-dependent genes. In this study, we performed molecular dynamics simulations on the active and inactive dimers and monomers of the PhoP regulatory domains, followed by pocket-detecting screenings and a quantitative hot-spot analysis in order to assess the druggability of the protein. Consistent with prior hypothesis, the calculation of the binding free energy shows that phosphorylation enhances dimerization of PhoP. Furthermore, we have identified two different putative binding sites at the dimerization active site (the α4-β5-α5 face) with energetic "hot-spot" areas, which could be used to search for modulators of protein-protein interactions. This study delivers insight into the dynamics and druggability of the dimerization interface of the PhoP regulatory domain, and may serve as a basis for the rational identification of new antimicrobial drugs. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Barriers and enablers to implementing antenatal magnesium sulphate for fetal neuroprotection guidelines: a study using the theoretical domains framework.

    Science.gov (United States)

    Bain, Emily; Bubner, Tanya; Ashwood, Pat; Van Ryswyk, Emer; Simmonds, Lucy; Reid, Sally; Middleton, Philippa; Crowther, Caroline A

    2015-08-18

    Strong evidence supports administration of magnesium sulphate prior to birth at less than 30 weeks' gestation to prevent very preterm babies dying or developing cerebral palsy. This study was undertaken as part of The WISH (Working to Improve Survival and Health for babies born very preterm) Project, to assess health professionals' self-reported use of antenatal magnesium sulphate, and barriers and enablers to implementation of 2010 Australian and New Zealand clinical practice guidelines. Semi-structured, one-to-one interviews were conducted with obstetric and neonatal consultants and trainees, and midwives in 2011 (n = 24) and 2012-2013 (n = 21) at the Women's and Children's Hospital, South Australia. Transcribed interview data were coded using the Theoretical Domains Framework (describing 14 domains related to behaviour change) for analysis of barriers and enablers. In 2012-13, health professionals more often reported 'routinely' or 'sometimes' administering or advising their colleagues to administer magnesium sulphate for fetal neuroprotection (86% in 2012-13 vs. 46% in 2011). 'Knowledge and skills', 'memory, attention and decision processes', 'environmental context and resources', 'beliefs about consequences' and 'social influences' were key domains identified in the barrier and enabler analysis. Perceived barriers were the complex administration processes, time pressures, and the unpredictability of preterm birth. Enablers included education for staff and women at risk of very preterm birth, reminders and 'prompts', simplified processes for administration, and influential colleagues. This study has provided valuable data on barriers and enablers to implementing magnesium sulphate for fetal neuroprotection, with implications for designing and modifying future behaviour change strategies, to ensure optimal uptake of this neuroprotective therapy for very preterm infants.

  5. Hierarchical modeling of activation mechanisms in the ABL and EGFR kinase domains: thermodynamic and mechanistic catalysts of kinase activation by cancer mutations.

    Directory of Open Access Journals (Sweden)

    Anshuman Dixit

    2009-08-01

    Full Text Available Structural and functional studies of the ABL and EGFR kinase domains have recently suggested a common mechanism of activation by cancer-causing mutations. However, dynamics and mechanistic aspects of kinase activation by cancer mutations that stimulate conformational transitions and thermodynamic stabilization of the constitutively active kinase form remain elusive. We present a large-scale computational investigation of activation mechanisms in the ABL and EGFR kinase domains by a panel of clinically important cancer mutants ABL-T315I, ABL-L387M, EGFR-T790M, and EGFR-L858R. We have also simulated the activating effect of the gatekeeper mutation on conformational dynamics and allosteric interactions in functional states of the ABL-SH2-SH3 regulatory complexes. A comprehensive analysis was conducted using a hierarchy of computational approaches that included homology modeling, molecular dynamics simulations, protein stability analysis, targeted molecular dynamics, and molecular docking. Collectively, the results of this study have revealed thermodynamic and mechanistic catalysts of kinase activation by major cancer-causing mutations in the ABL and EGFR kinase domains. By using multiple crystallographic states of ABL and EGFR, computer simulations have allowed one to map dynamics of conformational fluctuations and transitions in the normal (wild-type and oncogenic kinase forms. A proposed multi-stage mechanistic model of activation involves a series of cooperative transitions between different conformational states, including assembly of the hydrophobic spine, the formation of the Src-like intermediate structure, and a cooperative breakage and formation of characteristic salt bridges, which signify transition to the active kinase form. We suggest that molecular mechanisms of activation by cancer mutations could mimic the activation process of the normal kinase, yet exploiting conserved structural catalysts to accelerate a conformational transition

  6. Potential determinants of health-care professionals' use of survivorship care plans: a qualitative study using the theoretical domains framework.

    Science.gov (United States)

    Birken, Sarah A; Presseau, Justin; Ellis, Shellie D; Gerstel, Adrian A; Mayer, Deborah K

    2014-11-15

    Survivorship care plans are intended to improve coordination of care for the nearly 14 million cancer survivors in the United States. Evidence suggests that survivorship care plans (SCPs) have positive outcomes for survivors, health-care professionals, and cancer programs, and several high-profile organizations now recommend SCP use. Nevertheless, SCP use remains limited among health-care professionals in United States cancer programs. Knowledge of barriers to SCP use is limited in part because extant studies have used anecdotal evidence to identify determinants. This study uses the theoretical domains framework to identify relevant constructs that are potential determinants of SCP use among United States health-care professionals. We conducted semi-structured interviews to assess the relevance of 12 theoretical domains in predicting SCP use among 13 health-care professionals in 7 cancer programs throughout the United States with diverse characteristics. Relevant theoretical domains were identified through thematic coding of interview transcripts, identification of specific beliefs within coded text units, and mapping of specific beliefs onto theoretical constructs. We found the following theoretical domains (based on specific beliefs) to be potential determinants of SCP use: health-care professionals' beliefs about the consequences of SCP use (benefit to survivors, health-care professionals, and the system as a whole); motivation and goals regarding SCP use (advocating SCP use; extent to which using SCPs competed for health-care professionals' time); environmental context and resources (whether SCPs were delivered at a dedicated visit and whether a system, information technology, and funding facilitated SCP use); and social influences (whether using SCPs is an organizational priority, influential people support SCP use, and people who could assist with SCP use buy into using SCPs). Specific beliefs mapped onto the following psychological constructs: outcome

  7. Study of the individual cytochrome b5 and cytochrome b5 reductase domains of Ncb5or reveals a unique heme pocket and a possible role of the CS domain.

    Science.gov (United States)

    Deng, Bin; Parthasarathy, Sudharsan; Wang, WenFang; Gibney, Brian R; Battaile, Kevin P; Lovell, Scott; Benson, David R; Zhu, Hao

    2010-09-24

    NADH cytochrome b(5) oxidoreductase (Ncb5or) is found in animals and contains three domains similar to cytochrome b(5) (b(5)), CHORD-SGT1 (CS), and cytochrome b(5) reductase (b(5)R). Ncb5or has an important function, as suggested by the diabetes and lipoatrophy phenotypes in Ncb5or null mice. To elucidate the structural and functional properties of human Ncb5or, we generated its individual b(5) and b(5)R domains (Ncb5or-b(5) and Ncb5or-b(5)R, respectively) and compared them with human microsomal b(5) (Cyb5A) and b(5)R (Cyb5R3). A 1.25 Å x-ray crystal structure of Ncb5or-b(5) reveals nearly orthogonal planes of the imidazolyl rings of heme-ligating residues His(89) and His(112), consistent with a highly anisotropic low spin EPR spectrum. Ncb5or is the first member of the cytochrome b(5) family shown to have such a heme environment. Like other b(5) family members, Ncb5or-b(5) has two helix-loop-helix motifs surrounding heme. However, Ncb5or-b(5) differs from Cyb5A with respect to location of the second heme ligand (His(112)) and of polypeptide conformation in its vicinity. Electron transfer from Ncb5or-b(5)R to Ncb5or-b(5) is much less efficient than from Cyb5R3 to Cyb5A, possibly as a consequence of weaker electrostatic interactions. The CS linkage probably obviates the need for strong interactions between b(5) and b(5)R domains in Ncb5or. Studies with a construct combining the Ncb5or CS and b(5)R domains suggest that the CS domain facilitates docking of the b(5) and b(5)R domains. Trp(114) is an invariant surface residue in all known Ncb5or orthologs but appears not to contribute to electron transfer from the b(5)R domain to the b(5) domain.

  8. Identification of Phytochemicals Targeting c-Met Kinase Domain using Consensus Docking and Molecular Dynamics Simulation Studies.

    Science.gov (United States)

    Aliebrahimi, Shima; Montasser Kouhsari, Shideh; Ostad, Seyed Nasser; Arab, Seyed Shahriar; Karami, Leila

    2018-06-01

    c-Met receptor tyrosine kinase is a proto-oncogene whose aberrant activation is attributed to a lower rate of survival in most cancers. Natural product-derived inhibitors known as "fourth generation inhibitors" constitute more than 60% of anticancer drugs. Furthermore, consensus docking approach has recently been introduced to augment docking accuracy and reduce false positives during a virtual screening. In order to obtain novel small-molecule Met inhibitors, consensus docking approach was performed using Autodock Vina and Autodock 4.2 to virtual screen Naturally Occurring Plant-based Anti-cancer Compound-Activity-Target database against active and inactive conformation of c-Met kinase domain structure. Two hit molecules that were in line with drug-likeness criteria, desired docking score, and binding pose were subjected to molecular dynamics simulations to elucidate intermolecular contacts in protein-ligand complexes. Analysis of molecular dynamics simulations and molecular mechanics Poisson-Boltzmann surface area studies showed that ZINC08234189 is a plausible inhibitor for the active state of c-Met, whereas ZINC03871891 may be more effective toward active c-Met kinase domain compared to the inactive form due to higher binding energy. Our analysis showed that both the hit molecules formed hydrogen bonds with key residues of the hinge region (P1158, M1160) in the active form, which is a hallmark of kinase domain inhibitors. Considering the pivotal role of HGF/c-Met signaling in carcinogenesis, our results propose ZINC08234189 and ZINC03871891 as the therapeutic options to surmount Met-dependent cancers.

  9. Kinase impact assessment in the landscape of fusion genes that retain kinase domains: a pan-cancer study

    Science.gov (United States)

    Kim, Pora; Jia, Peilin; Zhao, Zhongming

    2018-01-01

    Abstract Assessing the impact of kinase in gene fusion is essential for both identifying driver fusion genes (FGs) and developing molecular targeted therapies. Kinase domain retention is a crucial factor in kinase fusion genes (KFGs), but such a systematic investigation has not been done yet. To this end, we analyzed kinase domain retention (KDR) status in chimeric protein sequences of 914 KFGs covering 312 kinases across 13 major cancer types. Based on 171 kinase domain-retained KFGs including 101 kinases, we studied their recurrence, kinase groups, fusion partners, exon-based expression depth, short DNA motifs around the break points and networks. Our results, such as more KDR than 5′-kinase fusion genes, combinatorial effects between 3′-KDR kinases and their 5′-partners and a signal transduction-specific DNA sequence motif in the break point intronic sequences, supported positive selection on 3′-kinase fusion genes in cancer. We introduced a degree-of-frequency (DoF) score to measure the possible number of KFGs of a kinase. Interestingly, kinases with high DoF scores tended to undergo strong gene expression alteration at the break points. Furthermore, our KDR gene fusion network analysis revealed six of the seven kinases with the highest DoF scores (ALK, BRAF, MET, NTRK1, NTRK3 and RET) were all observed in thyroid carcinoma. Finally, we summarized common features of ‘effective’ (highly recurrent) kinases in gene fusions such as expression alteration at break point, redundant usage in multiple cancer types and 3′-location tendency. Collectively, our findings are useful for prioritizing driver kinases and FGs and provided insights into KFGs’ clinical implications. PMID:28013235

  10. Quality of life domains important and relevant to family caregivers of advanced cancer patients in an Asian population: a qualitative study.

    Science.gov (United States)

    Lee, Geok Ling; Ow, Mandy Yen Ling; Akhileswaran, Ramaswamy; Pang, Grace Su Yin; Fan, Gilbert Kam Tong; Goh, Brandon Huat Heng; Wong, Cai Fong; Cheung, Yin Bun; Wee, Hwee Lin

    2015-04-01

    This study aims to identify domains of quality of life (QoL) that are culturally relevant to Chinese caregivers of advanced cancer patients in Singapore and to evaluate content adequacy of currently available instruments for use in the target population. English- and Chinese-speaking caregivers of advanced cancer patients receiving care under a tertiary cancer center and/or a community hospice home care/day care provider were recruited for in-depth interviews. The interviews were analyzed using thematic analysis. The identified domains, themes and sub-themes were compared to concepts addressed by items from five existing cancer-specific caregiver QoL instruments. Eighteen female and eight male caregivers aged 28-74 years participated in the study. Twenty-nine QoL themes and 59 sub-themes were identified in six domains, namely physical health, mental health, social health, spiritual health, financial health and daily life. Collectively, but not individually, the content of the five existing instruments adequately cover the physical health domain, social health domain and some themes on mental health domain for the study population. Content gaps were identified in the domains of mental health, spiritual health, daily life and financial health. The present study found culturally and contextually specific themes and sub-themes about positive emotional health, spiritual health and financial health.

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

    International Nuclear Information System (INIS)

    Vognsen, Tina; Kristensen, Ole

    2012-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, S.M. [Department of Studies in Physics, University of Mysore, Mysore 570 006 (India); Pampa, K.J. [Department of Studies in Microbiology, University of Mysore, Mysore 570 006 (India); Manjula, M. [Department of Studies in Physics, University of Mysore, Mysore 570 006 (India); Abdoh, M.M.M. [Department of Physics, Faculty of Science, An-Najah National University, Nablus, West Bank, Palestine (Country Unknown); Kunishima, Naoki [Advanced Protein Crystallography Research Group, RIKEN SPring-8 Center, Harima Institute, Hyogo 679-5148 (Japan); Lokanath, N.K., E-mail: lokanath@physics.uni-mysore.ac.in [Department of Studies in Physics, University of Mysore, Mysore 570 006 (India)

    2014-06-20

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

  13. Feature-level domain adaptation

    DEFF Research Database (Denmark)

    Kouw, Wouter M.; Van Der Maaten, Laurens J P; Krijthe, Jesse H.

    2016-01-01

    -level domain adaptation (flda), that models the dependence between the two domains by means of a feature-level transfer model that is trained to describe the transfer from source to target domain. Subsequently, we train a domain-adapted classifier by minimizing the expected loss under the resulting transfer...... modeled via a dropout distribution, which allows the classiffier to adapt to differences in the marginal probability of features in the source and the target domain. Our experiments on several real-world problems show that flda performs on par with state-of-the-art domainadaptation techniques.......Domain adaptation is the supervised learning setting in which the training and test data are sampled from different distributions: training data is sampled from a source domain, whilst test data is sampled from a target domain. This paper proposes and studies an approach, called feature...

  14. Detailed Equivalent VSC-HVDC Modelling for Time Domain Harmonic Stability Studies in Wind Power Plants

    DEFF Research Database (Denmark)

    Glasdam, Jakob Bærholm; Bak, Claus Leth; Kocewiak, Lukasz Hubert

    2018-01-01

    system with 201 voltage levels, without loss of accuracy compared to conventional modelling of the converter. Harmonic stability is a core concern for both existing and future offshore wind power plants (OWPPs). A harmonic stability study will be undertaken with focus on the number of wind turbine...

  15. Changes in Domain Specific Self-Perception amongst Young People with Intellectual Disability: A Longitudinal Study

    Science.gov (United States)

    O'Byrne, Clara; Muldoon, Orla T.

    2018-01-01

    This study examines the changes that occur in multidimensional self-concept of adolescents with a diagnosis of intellectual disabilities, across gender and category of intellectual disability (borderline, mild, moderate) groups. A sample of 54 young people completed the Harter Self-Perception Profile. Using a three-wave longitudinal study…

  16. Optical characterization of agricultural pest insects: a methodological study in the spectral and time domains

    Science.gov (United States)

    Li, Y. Y.; Zhang, H.; Duan, Z.; Lian, M.; Zhao, G. Y.; Sun, X. H.; Hu, J. D.; Gao, L. N.; Feng, H. Q.; Svanberg, S.

    2016-08-01

    Identification of agricultural pest insects is an important aspect in insect research and agricultural monitoring. We have performed a methodological study of how spectroscopic techniques and wing-beat frequency analysis might provide relevant information. An optical system based on the combination of close-range remote sensing and reflectance spectroscopy was developed to study the optical characteristics of different flying insects, collected in Southern China. The results demonstrate that the combination of wing-beat frequency assessment and reflectance spectral analysis has the potential to successfully differentiate between insect species. Further, studies of spectroscopic characteristics of fixed specimen of insects, also from Central China, showed the possibility of refined agricultural pest identification. Here, in addition to reflectance recordings also laser-induced fluorescence spectra were investigated for all the species of insects under study and found to provide complementary information to optically distinguish insects. In order to prove the practicality of the techniques explored, clearly fieldwork aiming at elucidating the variability of parameters, even within species, must be performed.

  17. Simulation studies of pore and domain formation in a phospholipid monolayer

    NARCIS (Netherlands)

    Knecht, Volker; Muller, M; Bonn, M; Marrink, SJ; Mark, AE

    2005-01-01

    Despite extensive study the phase behavior of phospholipid monolayers at an air-water interface is still not fully understood. In particular recent vibrational sum-frequency generation (VSFG) spectra of DPPC monolayers as a function of area density show a sharp transition in the order of the lipid

  18. Study of mechanically stimulated ferroelectric domain formation using scanning probe microscope

    Energy Technology Data Exchange (ETDEWEB)

    Kim, J H; Baek, J; Khim, Z G [School of Physics and Nano-Systems Institute, Seoul National University, Seoul 151-747 (Korea, Republic of)

    2007-03-15

    The stress-related ferroelectric properties have been studied on the Triglycine sulfate (TGS) by scanning probe microscope (SPM). Together with normal stress of the tip, the lateral stress is applied to the sample with piezoelectric transducers. With this study, we characterized the way the ferroelectricity of TGS responds to the axis-specific stress. Specially, the b-directional stress applicable to the surface can amount to several GPa such that the polarization switching by mechanical stress is observable. Although the lateral stress is not strong enough to view such phenomena, a-axis(c-axis) stress still affects the polarization value so as to fortify (lessen) the electric field inside, respectively. These contrasting results can be explained by the sign relation of piezo-coefficients about the individual axis. This work can be a touchstone of future researches in characterizing the electromechanical properties of more popular ferroelectrics such as PZT or BTO.

  19. Numerical study of influence of inlet turbulence parameters on turbulence intensity in the flow domain

    DEFF Research Database (Denmark)

    Jensen, Bo Boye Busk

    2007-01-01

    an electrochemical method. For optimization of process equipment with respect to cleaning, the levels of local fluctuations across entire surfaces are needed. Trends of fluctuations in the geometries used can be predicted using computational fluid dynamics (CFD). Two sensitivity studies were carried out......The prediction of cleaning in pipe-lines is important for equipment manufacturers, who wish to optimize designs with respect to hygienic performance. Degree of cleaning correlates with the level of fluctuations in the signal recorded in discrete points during wall shear stress measurements using...... profile trend estimated by use of CFD was found, whereas for the shortened geometry a great sensitivity in the estimated fluctuation profile trend when changing inlet conditions was seen. In the process Star-CD and Fluent (used in the present study) were compared and showed comparable predictions...

  20. The influence of microorganisms on the atmosphere and tools for the study of transacylase domains

    OpenAIRE

    Michaud, Jennifer M

    2017-01-01

    Specific biochemical influences on sea spray aerosol (SSA) are not well characterized and are vital to understanding the complex and variable chemical composition and atmospheric properties of SSA. Several studies reported in this thesis explore how microorganisms affect SSA both by examining their metabolic products in seawater and how they transfer from the seawater to aerosol, as well as the impacts of airborne microbes on SSA properties. To investigate the influence of microbial metabolis...

  1. Diabetes induces changes in neuroretina before retinal vessels: a spectral-domain optical coherence tomography study

    OpenAIRE

    Rodrigues, Eduardo B?chele; Urias, M?ller Gon?alves; Penha, Fernando Marcondes; Badar?, Emmerson; Novais, Eduardo; Meirelles, Rodrigo; Farah, Michel Eid

    2015-01-01

    Purpose To investigate retinal changes prior to vascular signs in patients with type 2 diabetes without diabetic retinopathy or with mild non proliferative diabetic retinopathy. Methods A cross-sectional study was performed in three groups: patients without diabetes, patients with type 2 diabetes without diabetic retinopathy, and patients with diabetes with mild diabetic retinopathy. Analysis of retinal layers was performed objectively with the Cirrus Review Software 6.0 (Carl Zeiss Meditec, ...

  2. Crystal Structure of the FERM Domain of Focal Adhesion Kinase

    International Nuclear Information System (INIS)

    Ceccarelli, D.; Song, H.; Poy, F.; Schaller, M.; Eck, M.

    2006-01-01

    Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that localizes to focal adhesions in adherent cells. Through phosphorylation of proteins assembled at the cytoplasmic tails of integrins, FAK promotes signaling events that modulate cellular growth, survival, and migration. The amino-terminal region of FAK contains a region of sequence homology with band 4.1 and ezrin/radixin/moesin (ERM) proteins termed a FERM domain. FERM domains are found in a variety of signaling and cytoskeletal proteins and are thought to mediate intermolecular interactions with partner proteins and phospholipids at the plasma membrane and intramolecular regulatory interactions. Here we report two crystal structures of an NH2-terminal fragment of avian FAK containing the FERM domain and a portion of the regulatory linker that connects the FERM and kinase domains. The tertiary folds of the three subdomains (F1, F2, and F3) are similar to those of known FERM structures despite low sequence conservation. Differences in the sequence and relative orientation of the F3 subdomain alters the nature of the interdomain interface, and the phosphoinositide binding site found in ERM family FERM domains is not present in FAK. A putative protein interaction site on the F3 lobe is masked by the proximal region of the linker. Additionally, in one structure the adjacent Src SH3 and SH2 binding sites in the linker associate with the surfaces of the F3 and F1 lobes, respectively. These structural features suggest the possibility that protein interactions of the FAK FERM domain can be regulated by binding of Src kinases to the linker segment

  3. Membrane docking geometry of GRP1 PH domain bound to a target lipid bilayer: an EPR site-directed spin-labeling and relaxation study.

    Directory of Open Access Journals (Sweden)

    Huai-Chun Chen

    Full Text Available The second messenger lipid PIP(3 (phosphatidylinositol-3,4,5-trisphosphate is generated by the lipid kinase PI3K (phosphoinositide-3-kinase in the inner leaflet of the plasma membrane, where it regulates a broad array of cell processes by recruiting multiple signaling proteins containing PIP(3-specific pleckstrin homology (PH domains to the membrane surface. Despite the broad importance of PIP(3-specific PH domains, the membrane docking geometry of a PH domain bound to its target PIP(3 lipid on a bilayer surface has not yet been experimentally determined. The present study employs EPR site-directed spin labeling and relaxation methods to elucidate the membrane docking geometry of GRP1 PH domain bound to bilayer-embedded PIP(3. The model target bilayer contains the neutral background lipid PC and both essential targeting lipids: (i PIP(3 target lipid that provides specificity and affinity, and (ii PS facilitator lipid that enhances the PIP(3 on-rate via an electrostatic search mechanism. The EPR approach measures membrane depth parameters for 18 function-retaining spin labels coupled to the PH domain, and for calibration spin labels coupled to phospholipids. The resulting depth parameters, together with the known high resolution structure of the co-complex between GRP1 PH domain and the PIP(3 headgroup, provide sufficient constraints to define an optimized, self-consistent membrane docking geometry. In this optimized geometry the PH domain engulfs the PIP(3 headgroup with minimal bilayer penetration, yielding the shallowest membrane position yet described for a lipid binding domain. This binding interaction displaces the PIP(3 headgroup from its lowest energy position and orientation in the bilayer, but the headgroup remains within its energetically accessible depth and angular ranges. Finally, the optimized docking geometry explains previous biophysical findings including mutations observed to disrupt membrane binding, and the rapid lateral

  4. Modeling induced polarization effects in helicopter time domain electromagnetic data: Synthetic case studies

    DEFF Research Database (Denmark)

    Viezzoli, Andrea; Kaminskiy, Vladislav; Fiandaca, Gianluca

    2017-01-01

    constrained multiparametric inversion was evaluated, including recovery of chargeability distributions from shallow and deep targets based on analysis of induced polarization (IP) effects, simulated in airborne TDEM data. Different scenarios were studied, including chargeable targets associated...... processing and the effect of constraints, and a priori information. We have used a 1D layered earth model approximation and lateral constraints. Synthetic simulations were performed for several models and the corresponding Cole-Cole parameters. The possibility to recover these models by means of laterally...... the airborne electromagnetic is most sensitive (e.g., approximately 1 ms), it is possible to recover deep chargeable targets (to depths more than 130 m) in association with high electrical conductivity and in resistive environments. Furthermore, it was found that the recovery of a deep conductor, masked...

  5. Frontal brain activation during a working memory task: a time-domain fNIRS study

    Science.gov (United States)

    Molteni, E.; Baselli, G.; Bianchi, A. M.; Caffini, M.; Contini, D.; Spinelli, L.; Torricelli, A.; Cerutti, S.; Cubeddu, R.

    2009-02-01

    We evaluated frontal brain activation during a working memory task with graded levels of difficulty in a group of 19 healthy subjects, by means of time-resolved fNIRS technique. Brain activation was computed, and was then separated into a "block-related" and a "tonic" components. Load-related increases of blood oxygenation were studied for the four different levels of task difficulty. Generalized Linear Models were applied to the data in order to explore the metabolic processes occurring during the mental effort and, possibly, their involvement in short term memorization. Results attest the presence of a persistent attentional-related metabolic activity, superimposed to a task-related mnemonic contribution. Moreover, a systemic component probably deriving from the extra-cerebral capillary bed was detected.

  6. Crystallographic Study of Peptidoglycan Biosynthesis Enzyme MurD: Domain Movement Revisited.

    Directory of Open Access Journals (Sweden)

    Roman Šink

    Full Text Available The biosynthetic pathway of peptidoglycan, an essential component of bacterial cell wall, is a well-recognized target for antibiotic development. Peptidoglycan precursors are synthesized in the bacterial cytosol by various enzymes including the ATP-hydrolyzing Mur ligases, which catalyze the stepwise addition of amino acids to a UDP-MurNAc precursor to yield UDP-MurNAc-pentapeptide. MurD catalyzes the addition of D-glutamic acid to UDP-MurNAc-L-Ala in the presence of ATP; structural and biochemical studies have suggested the binding of the substrates with an ordered kinetic mechanism in which ligand binding inevitably closes the active site. In this work, we challenge this assumption by reporting the crystal structures of intermediate forms of MurD either in the absence of ligands or in the presence of small molecules. A detailed analysis provides insight into the events that lead to the closure of MurD and reveals that minor structural modifications contribute to major overall conformation alterations. These novel insights will be instrumental in the development of new potential antibiotics designed to target the peptidoglycan biosynthetic pathway.

  7. Study of continuous-wave domain fluorescence diffuse optical tomography for quality control on agricultural produce

    Energy Technology Data Exchange (ETDEWEB)

    Nadhira, Vebi, E-mail: vebi@tf.itb.ac.id; Kurniadi, Deddy, E-mail: vebi@tf.itb.ac.id; Juliastuti, E., E-mail: vebi@tf.itb.ac.id; Sutiswan, Adeline, E-mail: vebi@tf.itb.ac.id [Instrumentation and Control Research Group, Faculty of Industrial Technology, Institute Technology of Bandung, Ganesha 10 40132 Bandung (Indonesia)

    2014-03-24

    The importance of monitoring the quality of vegetables and fruits is prosperity by giving a competitive advantage for producer and providing a more healthy food for consumer. Diffuse Optical Tomography (DOT) is offering the possibility to detect the internal defects of the agricultural produce quality. Fluorescence diffuse optical tomography (FDOT) is the development of DOT, offering the possibilities to improve spatial resolution and to contrast image. The purpose of this research is to compare FDOT and DOT in forward analysis with continuous wave approach. The scattering and absorbing parameters of potatoes are used to represent the real condition. The object was illuminated by the NIR source from some positions on the boundary of object. A set of NIR detector are placed on the peripheral position of the object to measure the intensity of propagated or emitted light. In the simulation, we varied a condition of object then we analyzed the sensitivity of forward problem. The result of this study shows that FDOT has a better sensitivity than DOT and a better potential to monitor internal defects of agricultural produce because of the contrast value between optical and fluorescence properties of agricultural produce normal tissue and defects.

  8. Exclusive study of the formation and the decay of hot nuclei in the intermediate energy domain

    International Nuclear Information System (INIS)

    Saint-Laurent, F.

    1990-01-01

    A brief review of exclusive measurements performed at GANIL in order to study hot nuclei will be given. Heavy-ion induced reactions on heavy targets have been investigated over a wide range of incident energy, using various techniques: - fission fragment angular correlations. - 4 π neutron multiplicity measurements. - light charged particle correlations. In each case, a selection of the most violent collisions can be achieved. For central collisions induced by 40 Ar, a same excitation energy of about 650 MeV is deduced from the totally different and independent sets of data, corresponding to an average temperature of 5 MeV. At 60 MeV/u, this value is quite low as compare to the total available energy for central collisions A tentative explanation based on Landau-Vlasov simulations will be proposed: the excitation energy dissipated in the system could be stored in a highly excited compression mode as well as under a thermal form. Some recent results on the Kr+Au system at 32 MeV/u will be presented indicating that heavier projectiles than 40 Ar can lead to a temperature of the hot system approaching 7 MeV

  9. Structure and degeneracy of vortex lattice domains in pure superconducting niobium: A small-angle neutron scattering study

    DEFF Research Database (Denmark)

    Laver, M.; Bowell, C.J.; Forgan, E.M.

    2009-01-01

    High-purity niobium exhibits a surprisingly rich assortment of vortex lattice (VL) structures for fields applied parallel to a fourfold symmetry axis, with all observed VL phases made up of degenerate domains that spontaneously break some crystal symmetry. Yet a single regular hexagonal VL domain...

  10. Evaluation of precipitation extremes over the Asian domain: observation and modelling studies

    Science.gov (United States)

    Kim, In-Won; Oh, Jaiho; Woo, Sumin; Kripalani, R. H.

    2018-04-01

    In this study, a comparison in the precipitation extremes as exhibited by the seven reference datasets is made to ascertain whether the inferences based on these datasets agree or they differ. These seven datasets, roughly grouped in three categories i.e. rain-gauge based (APHRODITE, CPC-UNI), satellite-based (TRMM, GPCP1DD) and reanalysis based (ERA-Interim, MERRA, and JRA55), having a common data period 1998-2007 are considered. Focus is to examine precipitation extremes in the summer monsoon rainfall over South Asia, East Asia and Southeast Asia. Measures of extreme precipitation include the percentile thresholds, frequency of extreme precipitation events and other quantities. Results reveal that the differences in displaying extremes among the datasets are small over South Asia and East Asia but large differences among the datasets are displayed over the Southeast Asian region including the maritime continent. Furthermore, precipitation data appear to be more consistent over East Asia among the seven datasets. Decadal trends in extreme precipitation are consistent with known results over South and East Asia. No trends in extreme precipitation events are exhibited over Southeast Asia. Outputs of the Coupled Model Intercomparison Project Phase 5 (CMIP5) simulation data are categorized as high, medium and low-resolution models. The regions displaying maximum intensity of extreme precipitation appear to be dependent on model resolution. High-resolution models simulate maximum intensity of extreme precipitation over the Indian sub-continent, medium-resolution models over northeast India and South China and the low-resolution models over Bangladesh, Myanmar and Thailand. In summary, there are differences in displaying extreme precipitation statistics among the seven datasets considered here and among the 29 CMIP5 model data outputs.

  11. Preliminary study on performance of a coupled hydrodynamic and sediment transport model on small domain

    Science.gov (United States)

    Rasyif, Teuku M.; Kato, Shigeru; Syamsidik, Okabe, Takumi

    2017-10-01

    Numerical simulation is one of the useful tools to analyze natural phenomena in the earth such as the tsunami disaster. Several numerical models can simulate the tsunami wave from its generation, propagation, and inundation. However, most tsunami models do not include the sediment transport module. The tsunami wave actually induces a lot of sediment during the propagation in the coastal area. In the case of Indian Ocean Tsunami in 2004, massive morphological changes were caused by the tsunami waves around Sumatra coast. In Aceh, some areas eroded by the tsunami wave were living place for a local community. It is indispensable for the resident in the coastal area to estimate the risk of morphological changes due to a tsunami wave. Therefore, a model that can investigate the morphological changes due tsunami wave is necessary. The result of this model can be used to consider a countermeasure for tsunami wave impact in the coastal area, such as land-use management and planning. The COMCOT-SED model had been developed by several researchers. This model combines the hydrodynamic module and the sediment module. The aim of this study is to get general information about performance of the COMCOT-SED model and to modify the model for more accurate results. Firstly, the model was demonstrated in the ideal condition to confirm the model validity. Then, we evaluated the model performance comparing the model results and the laboratory experiment data which was conducted by other researcher. The authors found that the results of water level and bottom profile by the original model in the ideal condition are not suitable. The model modification will give us more suitable results. The modified model will be applied to simulate the tsunami wave and sediment transport in the small area.

  12. Process and domain specificity in regions engaged for face processing: an fMRI study of perceptual differentiation.

    Science.gov (United States)

    Collins, Heather R; Zhu, Xun; Bhatt, Ramesh S; Clark, Jonathan D; Joseph, Jane E

    2012-12-01

    The degree to which face-specific brain regions are specialized for different kinds of perceptual processing is debated. This study parametrically varied demands on featural, first-order configural, or second-order configural processing of faces and houses in a perceptual matching task to determine the extent to which the process of perceptual differentiation was selective for faces regardless of processing type (domain-specific account), specialized for specific types of perceptual processing regardless of category (process-specific account), engaged in category-optimized processing (i.e., configural face processing or featural house processing), or reflected generalized perceptual differentiation (i.e., differentiation that crosses category and processing type boundaries). ROIs were identified in a separate localizer run or with a similarity regressor in the face-matching runs. The predominant principle accounting for fMRI signal modulation in most regions was generalized perceptual differentiation. Nearly all regions showed perceptual differentiation for both faces and houses for more than one processing type, even if the region was identified as face-preferential in the localizer run. Consistent with process specificity, some regions showed perceptual differentiation for first-order processing of faces and houses (right fusiform face area and occipito-temporal cortex and right lateral occipital complex), but not for featural or second-order processing. Somewhat consistent with domain specificity, the right inferior frontal gyrus showed perceptual differentiation only for faces in the featural matching task. The present findings demonstrate that the majority of regions involved in perceptual differentiation of faces are also involved in differentiation of other visually homogenous categories.

  13. Process- and Domain-Specificity in Regions Engaged for Face Processing: An fMRI Study of Perceptual Differentiation

    Science.gov (United States)

    Collins, Heather R.; Zhu, Xun; Bhatt, Ramesh S.; Clark, Jonathan D.; Joseph, Jane E.

    2015-01-01

    The degree to which face-specific brain regions are specialized for different kinds of perceptual processing is debated. The present study parametrically varied demands on featural, first-order configural or second-order configural processing of faces and houses in a perceptual matching task to determine the extent to which the process of perceptual differentiation was selective for faces regardless of processing type (domain-specific account), specialized for specific types of perceptual processing regardless of category (process-specific account), engaged in category-optimized processing (i.e., configural face processing or featural house processing) or reflected generalized perceptual differentiation (i.e. differentiation that crosses category and processing type boundaries). Regions of interest were identified in a separate localizer run or with a similarity regressor in the face-matching runs. The predominant principle accounting for fMRI signal modulation in most regions was generalized perceptual differentiation. Nearly all regions showed perceptual differentiation for both faces and houses for more than one processing type, even if the region was identified as face-preferential in the localizer run. Consistent with process-specificity, some regions showed perceptual differentiation for first-order processing of faces and houses (right fusiform face area and occipito-temporal cortex, and right lateral occipital complex), but not for featural or second-order processing. Somewhat consistent with domain-specificity, the right inferior frontal gyrus showed perceptual differentiation only for faces in the featural matching task. The present findings demonstrate that the majority of regions involved in perceptual differentiation of faces are also involved in differentiation of other visually homogenous categories. PMID:22849402

  14. Machine learning approaches to evaluate correlation patterns in allosteric signaling: A case study of the PDZ2 domain

    Science.gov (United States)

    Botlani, Mohsen; Siddiqui, Ahnaf; Varma, Sameer

    2018-06-01

    Many proteins are regulated by dynamic allostery wherein regulator-induced changes in structure are comparable with thermal fluctuations. Consequently, understanding their mechanisms requires assessment of relationships between and within conformational ensembles of different states. Here we show how machine learning based approaches can be used to simplify this high-dimensional data mining task and also obtain mechanistic insight. In particular, we use these approaches to investigate two fundamental questions in dynamic allostery. First, how do regulators modify inter-site correlations in conformational fluctuations (Cij)? Second, how are regulator-induced shifts in conformational ensembles at two different sites in a protein related to each other? We address these questions in the context of the human protein tyrosine phosphatase 1E's PDZ2 domain, which is a model protein for studying dynamic allostery. We use molecular dynamics to generate conformational ensembles of the PDZ2 domain in both the regulator-bound and regulator-free states. The employed protocol reproduces methyl deuterium order parameters from NMR. Results from unsupervised clustering of Cij combined with flow analyses of weighted graphs of Cij show that regulator binding significantly alters the global signaling network in the protein; however, not by altering the spatial arrangement of strongly interacting amino acid clusters but by modifying the connectivity between clusters. Additionally, we find that regulator-induced shifts in conformational ensembles, which we evaluate by repartitioning ensembles using supervised learning, are, in fact, correlated. This correlation Δij is less extensive compared to Cij, but in contrast to Cij, Δij depends inversely on the distance from the regulator binding site. Assuming that Δij is an indicator of the transduction of the regulatory signal leads to the conclusion that the regulatory signal weakens with distance from the regulatory site. Overall, this

  15. Compaction and binding properties of the intrinsically disordered C-terminal domain of Henipavirus nucleoprotein as unveiled by deletion studies.

    Science.gov (United States)

    Blocquel, David; Habchi, Johnny; Gruet, Antoine; Blangy, Stéphanie; Longhi, Sonia

    2012-01-01

    Henipaviruses are recently emerged severe human pathogens within the Paramyxoviridae family. Their genome is encapsidated by the nucleoprotein (N) within a helical nucleocapsid that recruits the polymerase complex via the phosphoprotein (P). We have previously shown that in Henipaviruses the N protein possesses an intrinsically disordered C-terminal domain, N(TAIL), which undergoes α-helical induced folding in the presence of the C-terminal domain (P(XD)) of the P protein. Using computational approaches, we previously identified within N(TAIL) four putative molecular recognition elements (MoREs) with different structural propensities, and proposed a structural model for the N(TAIL)-P(XD) complex where the MoRE encompassing residues 473-493 adopt an α-helical conformation at the P(XD) surface. In this work, for each N(TAIL) protein, we designed four deletion constructs bearing different combinations of the predicted MoREs. Following purification of the N(TAIL) truncated proteins from the soluble fraction of E. coli, we characterized them in terms of their conformational, spectroscopic and binding properties. These studies provided direct experimental evidence for the structural state of the four predicted MoREs, and showed that two of them have clear α-helical propensities, with the one spanning residues 473-493 being strictly required for binding to P(XD). We also showed that Henipavirus N(TAIL) and P(XD) form heterologous complexes, indicating that the P(XD) binding regions are functionally interchangeable between the two viruses. By combining spectroscopic and conformational analyses, we showed that the content in regular secondary structure is not a major determinant of protein compaction.

  16. Expansion of protein domain repeats.

    Directory of Open Access Journals (Sweden)

    Asa K Björklund

    2006-08-01

    Full Text Available Many proteins, especially in eukaryotes, contain tandem repeats of several domains from the same family. These repeats have a variety of binding properties and are involved in protein-protein interactions as well as binding to other ligands such as DNA and RNA. The rapid expansion of protein domain repeats is assumed to have evolved through internal tandem duplications. However, the exact mechanisms behind these tandem duplications are not well-understood. Here, we have studied the evolution, function, protein structure, gene structure, and phylogenetic distribution of domain repeats. For this purpose we have assigned Pfam-A domain families to 24 proteomes with more sensitive domain assignments in the repeat regions. These assignments confirmed previous findings that eukaryotes, and in particular vertebrates, contain a much higher fraction of proteins with repeats compared with prokaryotes. The internal sequence similarity in each protein revealed that the domain repeats are often expanded through duplications of several domains at a time, while the duplication of one domain is less common. Many of the repeats appear to have been duplicated in the middle of the repeat region. This is in strong contrast to the evolution of other proteins that mainly works through additions of single domains at either terminus. Further, we found that some domain families show distinct duplication patterns, e.g., nebulin domains have mainly been expanded with a unit of seven domains at a time, while duplications of other domain families involve varying numbers of domains. Finally, no common mechanism for the expansion of all repeats could be detected. We found that the duplication patterns show no dependence on the size of the domains. Further, repeat expansion in some families can possibly be explained by shuffling of exons. However, exon shuffling could not have created all repeats.

  17. Learning curves, taking instructions, and patient safety: using a theoretical domains framework in an interview study to investigate prescribing errors among trainee doctors

    Directory of Open Access Journals (Sweden)

    Duncan Eilidh M

    2012-09-01

    Full Text Available Abstract Background Prescribing errors are a major source of morbidity and mortality and represent a significant patient safety concern. Evidence suggests that trainee doctors are responsible for most prescribing errors. Understanding the factors that influence prescribing behavior may lead to effective interventions to reduce errors. Existing investigations of prescribing errors have been based on Human Error Theory but not on other relevant behavioral theories. The aim of this study was to apply a broad theory-based approach using the Theoretical Domains Framework (TDF to investigate prescribing in the hospital context among a sample of trainee doctors. Method Semistructured interviews, based on 12 theoretical domains, were conducted with 22 trainee doctors to explore views, opinions, and experiences of prescribing and prescribing errors. Content analysis was conducted, followed by applying relevance criteria and a novel stage of critical appraisal, to identify which theoretical domains could be targeted in interventions to improve prescribing. Results Seven theoretical domains met the criteria of relevance: “social professional role and identity,” “environmental context and resources,” “social influences,” “knowledge,” “skills,” “memory, attention, and decision making,” and “behavioral regulation.” From critical appraisal of the interview data, “beliefs about consequences” and “beliefs about capabilities” were also identified as potentially important domains. Interrelationships between domains were evident. Additionally, the data supported theoretical elaboration of the domain behavioral regulation. Conclusions In this investigation of hospital-based prescribing, participants’ attributions about causes of errors were used to identify domains that could be targeted in interventions to improve prescribing. In a departure from previous TDF practice, critical appraisal was used to identify additional domains

  18. Learning curves, taking instructions, and patient safety: using a theoretical domains framework in an interview study to investigate prescribing errors among trainee doctors.

    Science.gov (United States)

    Duncan, Eilidh M; Francis, Jill J; Johnston, Marie; Davey, Peter; Maxwell, Simon; McKay, Gerard A; McLay, James; Ross, Sarah; Ryan, Cristín; Webb, David J; Bond, Christine

    2012-09-11

    Prescribing errors are a major source of morbidity and mortality and represent a significant patient safety concern. Evidence suggests that trainee doctors are responsible for most prescribing errors. Understanding the factors that influence prescribing behavior may lead to effective interventions to reduce errors. Existing investigations of prescribing errors have been based on Human Error Theory but not on other relevant behavioral theories. The aim of this study was to apply a broad theory-based approach using the Theoretical Domains Framework (TDF) to investigate prescribing in the hospital context among a sample of trainee doctors. Semistructured interviews, based on 12 theoretical domains, were conducted with 22 trainee doctors to explore views, opinions, and experiences of prescribing and prescribing errors. Content analysis was conducted, followed by applying relevance criteria and a novel stage of critical appraisal, to identify which theoretical domains could be targeted in interventions to improve prescribing. Seven theoretical domains met the criteria of relevance: "social professional role and identity," "environmental context and resources," "social influences," "knowledge," "skills," "memory, attention, and decision making," and "behavioral regulation." From critical appraisal of the interview data, "beliefs about consequences" and "beliefs about capabilities" were also identified as potentially important domains. Interrelationships between domains were evident. Additionally, the data supported theoretical elaboration of the domain behavioral regulation. In this investigation of hospital-based prescribing, participants' attributions about causes of errors were used to identify domains that could be targeted in interventions to improve prescribing. In a departure from previous TDF practice, critical appraisal was used to identify additional domains that should also be targeted, despite participants' perceptions that they were not relevant to

  19. .Gov Domains API

    Data.gov (United States)

    General Services Administration — This dataset offers the list of all .gov domains, including state, local, and tribal .gov domains. It does not include .mil domains, or other federal domains outside...

  20. Dielectric dispersion, relaxation dynamics and thermodynamic studies of Beta-Alanine in aqueous solutions using picoseconds time domain reflectometry

    Science.gov (United States)

    Vinoth, K.; Ganesh, T.; Senthilkumar, P.; Sylvester, M. Maria; Karunakaran, D. J. S. Anand; Hudge, Praveen; Kumbharkhane, A. C.

    2017-09-01

    The aqueous solution of beta-alanine characterised and studied by their dispersive dielectric properties and relaxation process in the frequency domain of 10×106 Hz to 30×109 Hz with varying concentration in mole fractions and temperatures. The molecular interaction and dielectric parameters are discussed in terms of counter-ion concentration theory. The static permittivity (ε0), high frequency dielectric permittivity (ε∞) and excess dielectric parameters are accomplished by frequency depended physical properties and relaxation time (τ). Molecular orientation, ordering and correlation factors are reported as confirmation of intermolecular interactions. Ionic conductivity and thermo dynamical properties are concluded with the behaviour of the mixture constituents. Solute-solvent, solute-solute interaction, structure making and breaking abilities of the solute in aqueous medium are interpreted. Fourier Transform Infrared (FTIR) spectra of beta- alanine single crystal and liquid state have been studied. The 13C Nuclear Magnetic Resonance (NMR) spectral studies give the signature for resonating frequencies and chemical shifts of beta-alanine.

  1. Structure of a WW domain-containing fragment of dystrophin complexed with {beta}-dystroglycan.

    Energy Technology Data Exchange (ETDEWEB)

    Huang, X.; Poy, F.; Zhang, R.; Joachimiak, A.; Sudol, M.; Eck, M. J.; Biosciences Division; Dana Farber Cancer Inst.; Harvard Medical School; Mount Sinai School of Medicine

    2000-08-01

    Dystrophin and {beta}-dystroglycan are components of the dystrophin--glycoprotein complex (DGC), a multimolecular assembly that spans the cell membrane and links the actin cytoskeleton to the extracellular basal lamina. Defects in the dystrophin gene are the cause of Duchenne and Becker muscular dystrophies. The C-terminal region of dystrophin binds the cytoplasmic tail of {beta}-dystroglycan, in part through the interaction of its WW domain with a proline-rich motif in the tail of {beta}-dystroglycan. Here we report the crystal structure of this portion of dystrophin in complex with the proline-rich binding site in {beta}-dystroglycan. The structure shows that the dystrophin WW domain is embedded in an adjacent helical region that contains two EF-hand-like domains. The {beta}-dystroglycan peptide binds a composite surface formed by the WW domain and one of these EF-hands. Additionally, the structure reveals striking similarities in the mechanisms of proline recognition employed by WW domains and SH3 domains.

  2. Exploring behavioural determinants relating to health professional reporting of medication errors: a qualitative study using the Theoretical Domains Framework.

    Science.gov (United States)

    Alqubaisi, Mai; Tonna, Antonella; Strath, Alison; Stewart, Derek

    2016-07-01

    Effective and efficient medication reporting processes are essential in promoting patient safety. Few qualitative studies have explored reporting of medication errors by health professionals, and none have made reference to behavioural theories. The objective was to describe and understand the behavioural determinants of health professional reporting of medication errors in the United Arab Emirates (UAE). This was a qualitative study comprising face-to-face, semi-structured interviews within three major medical/surgical hospitals of Abu Dhabi, the UAE. Health professionals were sampled purposively in strata of profession and years of experience. The semi-structured interview schedule focused on behavioural determinants around medication error reporting, facilitators, barriers and experiences. The Theoretical Domains Framework (TDF; a framework of theories of behaviour change) was used as a coding framework. Ethical approval was obtained from a UK university and all participating hospital ethics committees. Data saturation was achieved after interviewing ten nurses, ten pharmacists and nine physicians. Whilst it appeared that patient safety and organisational improvement goals and intentions were behavioural determinants which facilitated reporting, there were key determinants which deterred reporting. These included the beliefs of the consequences of reporting (lack of any feedback following reporting and impacting professional reputation, relationships and career progression), emotions (fear and worry) and issues related to the environmental context (time taken to report). These key behavioural determinants which negatively impact error reporting can facilitate the development of an intervention, centring on organisational safety and reporting culture, to enhance reporting effectiveness and efficiency.

  3. Relationship between macular ganglion cell complex thickness and macular outer retinal thickness: a spectral-domain optical coherence tomography study.

    Science.gov (United States)

    Kita, Yoshiyuki; Kita, Ritsuko; Takeyama, Asuka; Anraku, Ayako; Tomita, Goji; Goldberg, Ivan

    2013-01-01

    To assess the relationship between macular ganglion cell complex and macular outer retinal thicknesses. Case-control study. Forty-two normal eyes and 91 eyes with primary open-angle glaucoma were studied. Spectral-domain optical coherence tomography (RTVue-100) was used to measure the macular ganglion cell complex and macular outer retinal thickness. Ganglion cell complex to outer retinal thickness ratio was also calculated. The relationships between the ganglion cell complex and outer retinal thicknesses and between the ganglion cell complex to outer retinal thickness ratio and outer retinal thickness were evaluated. There was a positive correlation between ganglion cell complex and outer retinal thicknesses in the normal group and the glaucoma group (r = 0.53, P variation in the outer retinal thickness. Therefore, when determining the ganglion cell complex, it seems necessary to consider the outer retinal thickness as well. We propose the ratio as a suitable parameter to account for individual variations in outer retinal thickness. © 2013 The Authors. Clinical and Experimental Ophthalmology © 2013 Royal Australian and New Zealand College of Ophthalmologists.

  4. Domain architecture conservation in orthologs

    Science.gov (United States)

    2011-01-01

    Background As orthologous proteins are expected to retain function more often than other homologs, they are often used for functional annotation transfer between species. However, ortholog identification methods do not take into account changes in domain architecture, which are likely to modify a protein's function. By domain architecture we refer to the sequential arrangement of domains along a protein sequence. To assess the level of domain architecture conservation among orthologs, we carried out a large-scale study of such events between human and 40 other species spanning the entire evolutionary range. We designed a score to measure domain architecture similarity and used it to analyze differences in domain architecture conservation between orthologs and paralogs relative to the conservation of primary sequence. We also statistically characterized the extents of different types of domain swapping events across pairs of orthologs and paralogs. Results The analysis shows that orthologs exhibit greater domain architecture conservation than paralogous homologs, even when differences in average sequence divergence are compensated for, for homologs that have diverged beyond a certain threshold. We interpret this as an indication of a stronger selective pressure on orthologs than paralogs to retain the domain architecture required for the proteins to perform a specific function. In general, orthologs as well as the closest paralogous homologs have very similar domain architectures, even at large evolutionary separation. The most common domain architecture changes observed in both ortholog and paralog pairs involved insertion/deletion of new domains, while domain shuffling and segment duplication/deletion were very infrequent. Conclusions On the whole, our results support the hypothesis that function conservation between orthologs demands higher domain architecture conservation than other types of homologs, relative to primary sequence conservation. This supports the

  5. Somatic, positive and negative domains of the Center for Epidemiological Studies Depression (CES-D) scale: a meta-analysis of genome-wide association studies.

    Science.gov (United States)

    Demirkan, A; Lahti, J; Direk, N; Viktorin, A; Lunetta, K L; Terracciano, A; Nalls, M A; Tanaka, T; Hek, K; Fornage, M; Wellmann, J; Cornelis, M C; Ollila, H M; Yu, L; Smith, J A; Pilling, L C; Isaacs, A; Palotie, A; Zhuang, W V; Zonderman, A; Faul, J D; Sutin, A; Meirelles, O; Mulas, A; Hofman, A; Uitterlinden, A; Rivadeneira, F; Perola, M; Zhao, W; Salomaa, V; Yaffe, K; Luik, A I; Liu, Y; Ding, J; Lichtenstein, P; Landén, M; Widen, E; Weir, D R; Llewellyn, D J; Murray, A; Kardia, S L R; Eriksson, J G; Koenen, K; Magnusson, P K E; Ferrucci, L; Mosley, T H; Cucca, F; Oostra, B A; Bennett, D A; Paunio, T; Berger, K; Harris, T B; Pedersen, N L; Murabito, J M; Tiemeier, H; van Duijn, C M; Räikkönen, K

    2016-06-01

    Major depressive disorder (MDD) is moderately heritable, however genome-wide association studies (GWAS) for MDD, as well as for related continuous outcomes, have not shown consistent results. Attempts to elucidate the genetic basis of MDD may be hindered by heterogeneity in diagnosis. The Center for Epidemiological Studies Depression (CES-D) scale provides a widely used tool for measuring depressive symptoms clustered in four different domains which can be combined together into a total score but also can be analysed as separate symptom domains. We performed a meta-analysis of GWAS of the CES-D symptom clusters. We recruited 12 cohorts with the 20- or 10-item CES-D scale (32 528 persons). One single nucleotide polymorphism (SNP), rs713224, located near the brain-expressed melatonin receptor (MTNR1A) gene, was associated with the somatic complaints domain of depression symptoms, with borderline genome-wide significance (p discovery = 3.82 × 10-8). The SNP was analysed in an additional five cohorts comprising the replication sample (6813 persons). However, the association was not consistent among the replication sample (p discovery+replication = 1.10 × 10-6) with evidence of heterogeneity. Despite the effort to harmonize the phenotypes across cohorts and participants, our study is still underpowered to detect consistent association for depression, even by means of symptom classification. On the contrary, the SNP-based heritability and co-heritability estimation results suggest that a very minor part of the variation could be captured by GWAS, explaining the reason of sparse findings.

  6. Laboratory study of nitrate photolysis in Antarctic snow. I. Observed quantum yield, domain of photolysis, and secondary chemistry

    Energy Technology Data Exchange (ETDEWEB)

    Meusinger, Carl; Johnson, Matthew S. [Department of Chemistry, University of Copenhagen, Copenhagen (Denmark); Berhanu, Tesfaye A.; Erbland, Joseph; Savarino, Joel, E-mail: jsavarino@lgge.obs.ujf-grenoble.fr [Univ. Grenoble Alpes, LGGE, F-38000 Grenoble (France); CNRS, LGGE, F-38000 Grenoble (France)

    2014-06-28

    Post-depositional processes alter nitrate concentration and nitrate isotopic composition in the top layers of snow at sites with low snow accumulation rates, such as Dome C, Antarctica. Available nitrate ice core records can provide input for studying past atmospheres and climate if such processes are understood. It has been shown that photolysis of nitrate in the snowpack plays a major role in nitrate loss and that the photolysis products have a significant influence on the local troposphere as well as on other species in the snow. Reported quantum yields for the main reaction spans orders of magnitude – apparently a result of whether nitrate is located at the air-ice interface or in the ice matrix – constituting the largest uncertainty in models of snowpack NO{sub x} emissions. Here, a laboratory study is presented that uses snow from Dome C and minimizes effects of desorption and recombination by flushing the snow during irradiation with UV light. A selection of UV filters allowed examination of the effects of the 200 and 305 nm absorption bands of nitrate. Nitrate concentration and photon flux were measured in the snow. The quantum yield for loss of nitrate was observed to decrease from 0.44 to 0.003 within what corresponds to days of UV exposure in Antarctica. The superposition of photolysis in two photochemical domains of nitrate in snow is proposed: one of photolabile nitrate, and one of buried nitrate. The difference lies in the ability of reaction products to escape the snow crystal, versus undergoing secondary (recombination) chemistry. Modeled NO{sub x} emissions may increase significantly above measured values due to the observed quantum yield in this study. The apparent quantum yield in the 200 nm band was found to be ∼1%, much lower than reported for aqueous chemistry. A companion paper presents an analysis of the change in isotopic composition of snowpack nitrate based on the same samples as in this study.

  7. Protein domain organisation: adding order

    Directory of Open Access Journals (Sweden)

    Kummerfeld Sarah K

    2009-01-01

    Full Text Available Abstract Background Domains are the building blocks of proteins. During evolution, they have been duplicated, fused and recombined, to produce proteins with novel structures and functions. Structural and genome-scale studies have shown that pairs or groups of domains observed together in a protein are almost always found in only one N to C terminal order and are the result of a single recombination event that has been propagated by duplication of the multi-domain unit. Previous studies of domain organisation have used graph theory to represent the co-occurrence of domains within proteins. We build on this approach by adding directionality to the graphs and connecting nodes based on their relative order in the protein. Most of the time, the linear order of domains is conserved. However, using the directed graph representation we have identified non-linear features of domain organization that are over-represented in genomes. Recognising these patterns and unravelling how they have arisen may allow us to understand the functional relationships between domains and understand how the protein repertoire has evolved. Results We identify groups of domains that are not linearly conserved, but instead have been shuffled during evolution so that they occur in multiple different orders. We consider 192 genomes across all three kingdoms of life and use domain and protein annotation to understand their functional significance. To identify these features and assess their statistical significance, we represent the linear order of domains in proteins as a directed graph and apply graph theoretical methods. We describe two higher-order patterns of domain organisation: clusters and bi-directionally associated domain pairs and explore their functional importance and phylogenetic conservation. Conclusion Taking into account the order of domains, we have derived a novel picture of global protein organization. We found that all genomes have a higher than expected

  8. Protein domain organisation: adding order.

    Science.gov (United States)

    Kummerfeld, Sarah K; Teichmann, Sarah A

    2009-01-29

    Domains are the building blocks of proteins. During evolution, they have been duplicated, fused and recombined, to produce proteins with novel structures and functions. Structural and genome-scale studies have shown that pairs or groups of domains observed together in a protein are almost always found in only one N to C terminal order and are the result of a single recombination event that has been propagated by duplication of the multi-domain unit. Previous studies of domain organisation have used graph theory to represent the co-occurrence of domains within proteins. We build on this approach by adding directionality to the graphs and connecting nodes based on their relative order in the protein. Most of the time, the linear order of domains is conserved. However, using the directed graph representation we have identified non-linear features of domain organization that are over-represented in genomes. Recognising these patterns and unravelling how they have arisen may allow us to understand the functional relationships between domains and understand how the protein repertoire has evolved. We identify groups of domains that are not linearly conserved, but instead have been shuffled during evolution so that they occur in multiple different orders. We consider 192 genomes across all three kingdoms of life and use domain and protein annotation to understand their functional significance. To identify these features and assess their statistical significance, we represent the linear order of domains in proteins as a directed graph and apply graph theoretical methods. We describe two higher-order patterns of domain organisation: clusters and bi-directionally associated domain pairs and explore their functional importance and phylogenetic conservation. Taking into account the order of domains, we have derived a novel picture of global protein organization. We found that all genomes have a higher than expected degree of clustering and more domain pairs in forward and

  9. GlycoDomainViewer

    DEFF Research Database (Denmark)

    Joshi, Hiren J; Jørgensen, Anja; Schjoldager, Katrine T

    2018-01-01

    features, which enhances visibility and accessibility of the wealth of glycoproteomic data being generated. The GlycoDomainViewer enables visual exploration of glycoproteomic data, incorporating information from recent N- and O-glycoproteome studies on human and animal cell lines and some organs and body...

  10. Analytical study on optically measured surface profiles of referential geometry using a finite-difference time-domain method

    International Nuclear Information System (INIS)

    Fujii, A; Hayashi, S; Fujii, S; Yanagi, K

    2014-01-01

    This paper deals with the functional performance of optical surface texture measuring instruments on the market. It is well known that their height response curves against certain referential geometry are not always identical to each other. So, a more precise study on the optical instrument's characteristics is greatly needed. Firstly, we developed a new simulation tool using a finite-difference time-domain technique, which enables the prediction of the height response curve against the fundamental surface geometry in the case of the confocal laser scanning microscope. Secondly, by utilizing this new simulation tool, measurement results, including outliers, were compared with the analytical simulation results. The comparison showed the consistency, which indicates that necessary conditions of surface measurement standards for verifying the instrument performance can be established. Consequently, we suggest that the maximum measurable slope angle must be added to evaluation subjects as significant metrological characteristics of measuring instruments, along with the lateral period limit. Finally, we propose a procedure to determine the lateral period limit in an ISO standard. (paper)

  11. Design of safety-critical systems using the complementarities of success and failure domains with a case study

    International Nuclear Information System (INIS)

    Ahmed, Rizwan; Koo, June Mo; Jeong, Yong Hoon; Heo, Gyunyoung

    2011-01-01

    A safety-critical system has to qualify the performance-related requirements and the safety-related requirements simultaneously. Conceptually, design processes should consider both of them simultaneously but the practices do not and/or cannot follow such a theoretical approach due to the limitation of design resources. From our experience, we found that safety-related functions must be simultaneously resolved with the development of performance-related functions, particularly, in case of safety-critical systems. Since, success and failure domain analyses are essential for the investigation of performance-related and safety-related requirements, respectively, we articulated our perception to Axiomatic Design (AD), Fault Tree Analysis (FTA), and TRIZ. A design evolution procedure considering feedbacks from AD to identify functional couplings, TRIZ methodology to explore uncoupling solutions and FTA to improve reliability in a systematic way is presented here. A case study regarding design of safety injection tank installed in a nuclear power plant is also included to illustrate the proposed framework. It is expected that several iterations between AD-TRIZ-FTA would result into an optimized design which could be tested against the desired performance and safety criteria.

  12. Domain-specificity of creativity: a study on the relationship between Visual Creativity and Visual Mental Imagery’.

    Directory of Open Access Journals (Sweden)

    Massimiliano ePalmiero

    2015-12-01

    Full Text Available Creativity refers to the capability to catch original and valuable ideas and solutions. It involves different processes. In this study the extent to which visual creativity is related to cognitive processes underlying visual mental imagery was investigated. Fifty college students (25 women carried out: the Creative Synthesis Task, which measures the ability to produce creative objects belonging to a given category (originality, synthesis and transformation scores of pre-inventive forms, and originality and practicality scores of inventions were computed; an adaptation of Clark’s Drawing Ability Test, which measures the ability to produce actual creative artworks (graphic ability, aesthetic and creativity scores of drawings were assessed and three mental imagery tasks that investigate the three main cognitive processes involved in visual mental imagery: generation, inspection and transformation. Vividness of imagery and verbalizer-visualizer cognitive style were also measured using questionnaires. Correlation analysis revealed that all measures of the creativity tasks positively correlated with the image transformation imagery ability; practicality of inventions negatively correlated with vividness of imagery; originality of inventions positively correlated with the visualization cognitive style. However, regression analysis confirmed the predictive role of the transformation imagery ability only for the originality score of inventions and for the graphic ability and aesthetic scores of artistic drawings; on the other hand, the visualization cognitive style predicted the originality of inventions, whereas the vividness of imagery predicted practicality of inventions. These results are consistent with the notion that visual creativity is domain- and task-specific.

  13. A two-domain real-time algorithm for optimal data reduction: A case study on accelerator magnet measurements

    CERN Document Server

    Arpaia, P; Inglese, V

    2010-01-01

    A real-time algorithm of data reduction, based on the combination a two lossy techniques specifically optimized for high-rate magnetic measurements in two domains (e.g. time and space), is proposed. The first technique exploits an adaptive sampling rule based on the power estimation of the flux increments in order to optimize the information to be gathered for magnetic field analysis in real time. The tracking condition is defined by the target noise level in the Nyquist band required by post-processing procedure of magnetic analysis. The second technique uses a data reduction algorithm in order to improve the compression ratio while preserving the consistency of the measured signal. The allowed loss is set equal to the random noise level in the signal in order to force the loss and the noise to cancel rather than to add, by improving the signal-to-noise ratio. Numerical analysis and experimental results of on-field performance characterization and validation for two case studies of magnetic measurement syste...

  14. A two-domain real-time algorithm for optimal data reduction: a case study on accelerator magnet measurements

    International Nuclear Information System (INIS)

    Arpaia, Pasquale; Buzio, Marco; Inglese, Vitaliano

    2010-01-01

    A real-time algorithm of data reduction, based on the combination of two lossy techniques specifically optimized for high-rate magnetic measurements in two domains (e.g. time and space), is proposed. The first technique exploits an adaptive sampling rule based on the power estimation of the flux increments in order to optimize the information to be gathered for magnetic field analysis in real time. The tracking condition is defined by the target noise level in the Nyquist band required by the post-processing procedure of magnetic analysis. The second technique uses a data reduction algorithm in order to improve the compression ratio while preserving the consistency of the measured signal. The allowed loss is set equal to the random noise level in the signal in order to force the loss and the noise to cancel rather than to add, by improving the signal-to-noise ratio. Numerical analysis and experimental results of on-field performance characterization and validation for two case studies of magnetic measurement systems for testing magnets of the Large Hadron Collider at the European Organization for Nuclear Research (CERN) are reported

  15. Design of safety-critical systems using the complementarities of success and failure domains with a case study

    Energy Technology Data Exchange (ETDEWEB)

    Ahmed, Rizwan; Koo, June Mo [Department of Nuclear Engineering, Kyung Hee University, Yongin-si, Gyeonggi-do 446-701 (Korea, Republic of); Jeong, Yong Hoon [Korea Advanced Institute of Science and Technology, 373-1 Guseong-dong, Yuseong-gu, Daejeon 305-701 (Korea, Republic of); Heo, Gyunyoung, E-mail: gheo@khu.ac.k [Department of Nuclear Engineering, Kyung Hee University, Yongin-si, Gyeonggi-do 446-701 (Korea, Republic of)

    2011-01-15

    A safety-critical system has to qualify the performance-related requirements and the safety-related requirements simultaneously. Conceptually, design processes should consider both of them simultaneously but the practices do not and/or cannot follow such a theoretical approach due to the limitation of design resources. From our experience, we found that safety-related functions must be simultaneously resolved with the development of performance-related functions, particularly, in case of safety-critical systems. Since, success and failure domain analyses are essential for the investigation of performance-related and safety-related requirements, respectively, we articulated our perception to Axiomatic Design (AD), Fault Tree Analysis (FTA), and TRIZ. A design evolution procedure considering feedbacks from AD to identify functional couplings, TRIZ methodology to explore uncoupling solutions and FTA to improve reliability in a systematic way is presented here. A case study regarding design of safety injection tank installed in a nuclear power plant is also included to illustrate the proposed framework. It is expected that several iterations between AD-TRIZ-FTA would result into an optimized design which could be tested against the desired performance and safety criteria.

  16. A cross-country comparison of intensive care physicians’ beliefs about their transfusion behaviour: A qualitative study using the theoretical domains framework

    Directory of Open Access Journals (Sweden)

    Islam Rafat

    2012-09-01

    Full Text Available Abstract Background Evidence of variations in red blood cell transfusion practices have been reported in a wide range of clinical settings. Parallel studies in Canada and the United Kingdom were designed to explore transfusion behaviour in intensive care physicians. The aim of this paper is three-fold: first, to explore beliefs that influence Canadian intensive care physicians’ transfusion behaviour; second, to systematically select relevant theories and models using the Theoretical Domains Framework (TDF to inform a future predictive study; and third, to compare its results with the UK study. Methods Ten intensive care unit (ICU physicians throughout Canada were interviewed. Physicians’ responses were coded into theoretical domains, and specific beliefs were generated for each response. Theoretical domains relevant to behaviour change were identified, and specific constructs from the relevant domains were used to select psychological theories. The results from Canada and the United Kingdom were compared. Results Seven theoretical domains populated by 31 specific beliefs were identified as relevant to the target behaviour. The domains Beliefs about capabilities (confident to not transfuse if patients’ clinical condition is stable, Beliefs about consequences (positive beliefs of reducing infection and saving resources and negative beliefs about risking patients’ clinical outcome and potentially more work, Social influences (transfusion decision is influenced by team members and patients’ relatives, and Behavioural regulation (wide range of approaches to encourage restrictive transfusion that were identified in the UK study were also relevant in the Canadian context. Three additional domains, Knowledge (it requires more evidence to support restrictive transfusion, Social/professional role and identity (conflicting beliefs about not adhering to guidelines, referring to evidence, believing restrictive transfusion as professional standard

  17. A cross-country comparison of intensive care physicians' beliefs about their transfusion behaviour: a qualitative study using the Theoretical Domains Framework.

    Science.gov (United States)

    Islam, Rafat; Tinmouth, Alan T; Francis, Jill J; Brehaut, Jamie C; Born, Jennifer; Stockton, Charlotte; Stanworth, Simon J; Eccles, Martin P; Cuthbertson, Brian H; Hyde, Chris; Grimshaw, Jeremy M

    2012-09-21

    Evidence of variations in red blood cell transfusion practices have been reported in a wide range of clinical settings. Parallel studies in Canada and the United Kingdom were designed to explore transfusion behaviour in intensive care physicians. The aim of this paper is three-fold: first, to explore beliefs that influence Canadian intensive care physicians' transfusion behaviour; second, to systematically select relevant theories and models using the Theoretical Domains Framework (TDF) to inform a future predictive study; and third, to compare its results with the UK study. Ten intensive care unit (ICU) physicians throughout Canada were interviewed. Physicians' responses were coded into theoretical domains, and specific beliefs were generated for each response. Theoretical domains relevant to behaviour change were identified, and specific constructs from the relevant domains were used to select psychological theories. The results from Canada and the United Kingdom were compared. Seven theoretical domains populated by 31 specific beliefs were identified as relevant to the target behaviour. The domains Beliefs about capabilities (confident to not transfuse if patients' clinical condition is stable), Beliefs about consequences (positive beliefs of reducing infection and saving resources and negative beliefs about risking patients' clinical outcome and potentially more work), Social influences (transfusion decision is influenced by team members and patients' relatives), and Behavioural regulation (wide range of approaches to encourage restrictive transfusion) that were identified in the UK study were also relevant in the Canadian context. Three additional domains, Knowledge (it requires more evidence to support restrictive transfusion), Social/professional role and identity (conflicting beliefs about not adhering to guidelines, referring to evidence, believing restrictive transfusion as professional standard, and believing that guideline is important for other

  18. A cross-country comparison of intensive care physicians’ beliefs about their transfusion behaviour: A qualitative study using the theoretical domains framework

    Science.gov (United States)

    2012-01-01

    Background Evidence of variations in red blood cell transfusion practices have been reported in a wide range of clinical settings. Parallel studies in Canada and the United Kingdom were designed to explore transfusion behaviour in intensive care physicians. The aim of this paper is three-fold: first, to explore beliefs that influence Canadian intensive care physicians’ transfusion behaviour; second, to systematically select relevant theories and models using the Theoretical Domains Framework (TDF) to inform a future predictive study; and third, to compare its results with the UK study. Methods Ten intensive care unit (ICU) physicians throughout Canada were interviewed. Physicians’ responses were coded into theoretical domains, and specific beliefs were generated for each response. Theoretical domains relevant to behaviour change were identified, and specific constructs from the relevant domains were used to select psychological theories. The results from Canada and the United Kingdom were compared. Results Seven theoretical domains populated by 31 specific beliefs were identified as relevant to the target behaviour. The domains Beliefs about capabilities (confident to not transfuse if patients’ clinical condition is stable), Beliefs about consequences (positive beliefs of reducing infection and saving resources and negative beliefs about risking patients’ clinical outcome and potentially more work), Social influences (transfusion decision is influenced by team members and patients’ relatives), and Behavioural regulation (wide range of approaches to encourage restrictive transfusion) that were identified in the UK study were also relevant in the Canadian context. Three additional domains, Knowledge (it requires more evidence to support restrictive transfusion), Social/professional role and identity (conflicting beliefs about not adhering to guidelines, referring to evidence, believing restrictive transfusion as professional standard, and believing that

  19. Validating Domains of Patient Contextual Factors Essential to Preventing Contextual Errors: A Qualitative Study Conducted at Chicago Area Veterans Health Administration Sites.

    Science.gov (United States)

    Binns-Calvey, Amy E; Malhiot, Alex; Kostovich, Carol T; LaVela, Sherri L; Stroupe, Kevin; Gerber, Ben S; Burkhart, Lisa; Weiner, Saul J; Weaver, Frances M

    2017-09-01

    "Patient context" indicates patient circumstances and characteristics or states that are essential to address when planning patient care. Specific patient "contextual factors," if overlooked, result in an inappropriate plan of care, a medical error termed a "contextual error." The myriad contextual factors that constitute patient context have been grouped into broad domains to create a taxonomy of challenges to consider when planning care. This study sought to validate a previously identified list of contextual domains. This qualitative study used directed content analysis. In 2014, 19 Department of Veterans Affairs (VA) providers (84% female) and 49 patients (86% male) from two VA medical centers and four outpatient clinics in the Chicago area participated in semistructured interviews and focus groups. Topics included patient-specific, community, and resource-related factors that affect patients' abilities to manage their care. Transcripts were analyzed with a previously identified list of contextual domains as a framework. Analysis of responses revealed that patients and providers identified the same 10 domains previously published, plus 3 additional ones. Based on comments made by patients and providers, the authors created a revised list of 12 domains from themes that emerged. Six pertain to patient circumstances such as access to care and financial situation, and 6 to patient characteristics/states including skills, abilities, and knowledge. Contextual factors in patients' lives may be essential to address for effective care planning. The rubric developed can serve as a "contextual differential" for clinicians to consider when addressing challenges patients face when planning their care.

  20. In silico studies on structure-function of DNA GCC- box binding domain of brassica napus DREB1 protein

    International Nuclear Information System (INIS)

    Qamarunnisa, S.; Hussain, M.

    2012-01-01

    DREB1 is a transcriptional factor, which selectively binds with the promoters of the genes involved in stress response in the plants. Homology of DREB protein and its binding element have been detected in the genome of many plants. However, only a few reports exist that discusses the binding properties of this protein with the gene (s) promoter. In the present study, we have undertaken studies exploring the structure-function relationship of Brassica napus DREB1. Multiple sequence alignment, protein homology modeling and intermolecular docking of GCC-box binding domain (GBD) of the said protein was carried out using atomic coordinates of GBD from Arabdiopsis thaliana and GCC-box containing DNA respectively. Similarities and/or identities in multiple, sequence alignment, particularly at the functionally important amino acids, strongly suggested the binding specificity of B. napus DREB1 to GCC-box. Similarly, despite 56% sequence homology, tertiary structures of both template and modeled protein were found to be extremely similar as indicated by root mean square deviation of 0.34 A. More similarities were established between GBD of both A. thaliana and B. napus DREB1 by conducting protein docking with the DNA containing GCC-box. It appears that both proteins interact through their beta-sheet with the major DNA groove including both nitrogen bases and phosphate and sugar moieties. Additionally, in most cases the interacting residues were also found to be identical. Briefly, this study attempts to elucidate the molecular basis of DREB1 interaction with its target sequence in the promoter. (author)

  1. Taxonomies of Educational Objective Domain

    OpenAIRE

    Eman Ghanem Nayef; Nik Rosila Nik Yaacob; Hairul Nizam Ismail

    2013-01-01

    This paper highlights an effort to study the educational objective domain taxonomies including Bloom’s taxonomy, Lorin Anderson’s taxonomy, and Wilson’s taxonomy. In this study a comparison among these three taxonomies have been done. Results show that Bloom’s taxonomy is more suitable as an analysis tool to Educational Objective domain.

  2. Effects of Increasing Neuromuscular Electrical Stimulation Current Intensity on Cortical Sensorimotor Network Activation: A Time Domain fNIRS Study.

    Directory of Open Access Journals (Sweden)

    Makii Muthalib

    Full Text Available Neuroimaging studies have shown neuromuscular electrical stimulation (NMES-evoked movements activate regions of the cortical sensorimotor network, including the primary sensorimotor cortex (SMC, premotor cortex (PMC, supplementary motor area (SMA, and secondary somatosensory area (S2, as well as regions of the prefrontal cortex (PFC known to be involved in pain processing. The aim of this study, on nine healthy subjects, was to compare the cortical network activation profile and pain ratings during NMES of the right forearm wrist extensor muscles at increasing current intensities up to and slightly over the individual maximal tolerated intensity (MTI, and with reference to voluntary (VOL wrist extension movements. By exploiting the capability of the multi-channel time domain functional near-infrared spectroscopy technique to relate depth information to the photon time-of-flight, the cortical and superficial oxygenated (O2Hb and deoxygenated (HHb hemoglobin concentrations were estimated. The O2Hb and HHb maps obtained using the General Linear Model (NIRS-SPM analysis method, showed that the VOL and NMES-evoked movements significantly increased activation (i.e., increase in O2Hb and corresponding decrease in HHb in the cortical layer of the contralateral sensorimotor network (SMC, PMC/SMA, and S2. However, the level and area of contralateral sensorimotor network (including PFC activation was significantly greater for NMES than VOL. Furthermore, there was greater bilateral sensorimotor network activation with the high NMES current intensities which corresponded with increased pain ratings. In conclusion, our findings suggest that greater bilateral sensorimotor network activation profile with high NMES current intensities could be in part attributable to increased attentional/pain processing and to increased bilateral sensorimotor integration in these cortical regions.

  3. On the influence of simulated SST warming on rainfall projections in the Indo-Pacific domain: an AGCM study

    Science.gov (United States)

    Zhang, Huqiang; Zhao, Y.; Moise, A.; Ye, H.; Colman, R.; Roff, G.; Zhao, M.

    2018-02-01

    Significant uncertainty exists in regional climate change projections, particularly for rainfall and other hydro-climate variables. In this study, we conduct a series of Atmospheric General Circulation Model (AGCM) experiments with different future sea surface temperature (SST) warming simulated by a range of coupled climate models. They allow us to assess the extent to which uncertainty from current coupled climate model rainfall projections can be attributed to their simulated SST warming. Nine CMIP5 model-simulated global SST warming anomalies have been super-imposed onto the current SSTs simulated by the Australian climate model ACCESS1.3. The ACCESS1.3 SST-forced experiments closely reproduce rainfall means and interannual variations as in its own fully coupled experiments. Although different global SST warming intensities explain well the inter-model difference in global mean precipitation changes, at regional scales the SST influence vary significantly. SST warming explains about 20-25% of the patterns of precipitation changes in each of the four/five models in its rainfall projections over the oceans in the Indo-Pacific domain, but there are also a couple of models in which different SST warming explains little of their precipitation pattern changes. The influence is weaker again for rainfall changes over land. Roughly similar levels of contribution can be attributed to different atmospheric responses to SST warming in these models. The weak SST influence in our study could be due to the experimental setup applied: superimposing different SST warming anomalies onto the same SSTs simulated for current climate by ACCESS1.3 rather than directly using model-simulated past and future SSTs. Similar modelling and analysis from other modelling groups with more carefully designed experiments are needed to tease out uncertainties caused by different SST warming patterns, different SST mean biases and different model physical/dynamical responses to the same underlying

  4. Prospective observational study on assessing the hemodynamic relevance of patent ductus arteriosus with frequency domain near-infrared spectroscopy.

    Science.gov (United States)

    Schwarz, Christoph E; Preusche, Antonio; Wolf, Martin; Poets, Christian F; Franz, Axel R

    2018-02-16

    What constitutes a hemodynamically relevant patent ductus arteriosus (hrPDA) in preterm infants is unclear. Different clinical and echocardiographic parameters are used, but a gold standard definition is lacking. Our objective was to evaluate associations between regional cerebral tissue oxygen saturation (rcStO 2 ), fraction of tissue oxygen extraction (rcFtO 2 E) measured by frequency domain near-infrared spectroscopy (fd-NIRS) and their correlation to echocardiographic, Doppler-ultrasound, and clinical parameters in preterm infants with and without a hrPDA. In this prospective observational study, 22 infants standard deviation (normalised to a median Hb of 13.8 mg/dl) was 57 ±5% for rcStO 2 and 0.39 ±0.05 for rcFtO 2 E. Comparing no-hrPDA with hrPDA infants, there were no significant differences in mean rcStO 2 (58 ±5% vs. 54 ±5%; p = .102), but in mean rcFtO 2 E (0.38 ±0.05 vs. 0.43 ±0.05; p = .038). Echocardiographic parameter and Doppler indices did not correlate with cerebral oxygenation. Oxygen transport capacity of the blood may confound NIRS data interpretation. Cerebral oxygenation determined by fd-NIRS provided additional information for PDA treatment decisions not offered by routine investigations. Whether indicating PDA therapy based on echocardiography complemented by data on cerebral oxygenation results in better outcomes should be investigated in future studies.

  5. Effects of Increasing Neuromuscular Electrical Stimulation Current Intensity on Cortical Sensorimotor Network Activation: A Time Domain fNIRS Study.

    Science.gov (United States)

    Muthalib, Makii; Re, Rebecca; Zucchelli, Lucia; Perrey, Stephane; Contini, Davide; Caffini, Matteo; Spinelli, Lorenzo; Kerr, Graham; Quaresima, Valentina; Ferrari, Marco; Torricelli, Alessandro

    2015-01-01

    Neuroimaging studies have shown neuromuscular electrical stimulation (NMES)-evoked movements activate regions of the cortical sensorimotor network, including the primary sensorimotor cortex (SMC), premotor cortex (PMC), supplementary motor area (SMA), and secondary somatosensory area (S2), as well as regions of the prefrontal cortex (PFC) known to be involved in pain processing. The aim of this study, on nine healthy subjects, was to compare the cortical network activation profile and pain ratings during NMES of the right forearm wrist extensor muscles at increasing current intensities up to and slightly over the individual maximal tolerated intensity (MTI), and with reference to voluntary (VOL) wrist extension movements. By exploiting the capability of the multi-channel time domain functional near-infrared spectroscopy technique to relate depth information to the photon time-of-flight, the cortical and superficial oxygenated (O2Hb) and deoxygenated (HHb) hemoglobin concentrations were estimated. The O2Hb and HHb maps obtained using the General Linear Model (NIRS-SPM) analysis method, showed that the VOL and NMES-evoked movements significantly increased activation (i.e., increase in O2Hb and corresponding decrease in HHb) in the cortical layer of the contralateral sensorimotor network (SMC, PMC/SMA, and S2). However, the level and area of contralateral sensorimotor network (including PFC) activation was significantly greater for NMES than VOL. Furthermore, there was greater bilateral sensorimotor network activation with the high NMES current intensities which corresponded with increased pain ratings. In conclusion, our findings suggest that greater bilateral sensorimotor network activation profile with high NMES current intensities could be in part attributable to increased attentional/pain processing and to increased bilateral sensorimotor integration in these cortical regions.

  6. Multifunctionalities driven by ferroic domains

    Science.gov (United States)

    Yang, J. C.; Huang, Y. L.; He, Q.; Chu, Y. H.

    2014-08-01

    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.

  7. Expression, purification, crystallization and preliminary X-ray studies of the Ebola VP35 interferon inhibitory domain

    International Nuclear Information System (INIS)

    Leung, Daisy W.; Ginder, Nathaniel D.; Nix, Jay C.; Basler, Christopher F.; Honzatko, Richard B.; Amarasinghe, Gaya K.

    2009-01-01

    Native and selenomethionine-labeled crystals of Ebola VP35 interferon inhibitory domain were obtained by the hanging-drop vapor-diffusion method. Ebola VP35 is a multifunctional protein that is important for host immune suppression and pathogenesis. VP35 contains an N-terminal oligomerization domain and a C-terminal interferon inhibitory domain (IID). Mutations within the VP35 IID result in loss of host immune suppression. Here, efforts to crystallize recombinantly overexpressed VP35 IID that was purified from Escherichia coli are described. Native and selenomethionine-labeled crystals belonging to the orthorhombic space group P2 1 2 1 2 1 were obtained by the hanging-drop vapor-diffusion method and diffraction data were collected at the ALS synchrotron

  8. Purification, crystallization and preliminary X-ray crystallographic studies of the Mycobacterium tuberculosis DNA gyrase ATPase domain

    International Nuclear Information System (INIS)

    Roué, Mélanie; Agrawal, Alka; Volker, Craig; Mossakowska, Danuta; Mayer, Claudine; Bax, Benjamin D.

    2013-01-01

    The ATPase domain of M. tuberculosis DNA gyrase was crystallized using hanging-drop vapour diffusion. The crystals belonged to space groups P1 and P2 1 . Diffraction data were collected to resolutions of 2.9 and 3.3 Å, respectively. Mycobacterium tuberculosis DNA gyrase, a nanomachine involved in the regulation of DNA topology, is the only type II topoisomerase present in this organism and hence is the sole target of fluoroquinolones in the treatment of tuberculosis. The ATPase domain provides the energy required for catalysis by ATP hydrolysis. Two constructs corresponding to this 43 kDa domain, Mtb-GyrB47 C1 and Mtb-GyrB47 C2 , have been overproduced, purified and crystallized. Diffraction data were collected from three crystal forms. The crystals belonged to space groups P1 and P2 1 and diffracted to resolutions of 2.9 and 3.3 Å, respectively

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

    Science.gov (United States)

    Vognsen, Tina; Kristensen, Ole

    2012-03-30

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

  10. Twin-domain size and bulk oxygen in-diffusion kinetics of YBa 2Cu 3O 6+x studied by neutron powder diffraction and gas volumetry

    Science.gov (United States)

    Poulsen, H. F.; Andersen, N. H.; Lebech, B.

    1991-02-01

    We report experimental results of twin-domain size and bulk oxygen in-diffusion kinetics of YBa 2Cu 3O 6+ x, which supplement a previous and simultaneous study of the structural phase diagram and oxygen equilibrium partial pressure. Analysis of neutron powder diffraction peak broadening show features which are identified to result from temperature independent twin-domain formation in to different orthorhombic phases with domain sizes and 250 and 350Å, respectively. The oxygen in-diffusion flow shows simple relaxation type behaviour J=J 0 exp( {-t}/{τ}) despite a rather broad particle size distribution. At higher temperatures, τ is activated with activation energies 0.55 and 0.25 eV in the tetragonal and orthorhombic phases, respectively. Comparison between twin-domain sizes and bulk oxygen in-diffusion time constants indicates that the twin-domain boundaries may contribute to the effective bulk oxygen in-diffusion. All our results may be interpreted in terms of the 2D ASYNNNI model description of the oxygen basal plane ordering, and they suggest that recent first principles interaction parameters should be modified.

  11. Domain wall networks on solitons

    International Nuclear Information System (INIS)

    Sutcliffe, Paul

    2003-01-01

    Domain wall networks on the surface of a soliton are studied in a simple theory. It consists of two complex scalar fields, in 3+1 dimensions, with a global U(1)xZ n symmetry, where n>2. Solutions are computed numerically in which one of the fields forms a Q ball and the other field forms a network of domain walls localized on the surface of the Q ball. Examples are presented in which the domain walls lie along the edges of a spherical polyhedron, forming junctions at its vertices. It is explained why only a small restricted class of polyhedra can arise as domain wall networks

  12. Off-Specular Synchrotron Moessbauer Reflectometry: A Novel Tool for Studying the Domain Structure in Antiferromagnetic Multilayers

    Energy Technology Data Exchange (ETDEWEB)

    Nagy, D. L.; Bottyan, L.; Deak, L. [KFKI Research Institute for Particle and Nuclear Physics (Hungary); Degroote, B.; Dekoster, J. [K.U. Leuven, Instituut voor Kern- en Stralingsfysica (Belgium); Leupold, O. [European Synchrotron Radiation Facility (France); Major, M. [KFKI Research Institute for Particle and Nuclear Physics (Hungary); Meersschaut, J. [K.U. Leuven, Instituut voor Kern- en Stralingsfysica (Belgium); Rueffer, R. [European Synchrotron Radiation Facility (France); Szilagyi, E. [KFKI Research Institute for Particle and Nuclear Physics (Hungary); Vantomme, A. [K.U. Leuven, Instituut voor Kern- en Stralingsfysica (Belgium)

    2002-06-15

    The off-specular (diffuse) nuclear resonant reflectivity of synchrotron radiation is a sensitive measure of the lateral autocorrelation of the magnetisation in thin films and multilayers. The width of the diffuse scattering peak measured at an electronically forbidden reflection is inversely proportional to the in-plane correlation length of the magnetisation direction. The average size of the in-plane antiferromagnetic domains is determined in different states of the same Fe/Cr superlattice. The hyperfine magnetic fields in coexisting small and large domains are measured independently.

  13. Sensitivity study of heavy precipitation in Limited Area Model climate simulations: influence of the size of the domain and the use of the spectral nudging technique

    Science.gov (United States)

    Colin, Jeanne; Déqué, Michel; Radu, Raluca; Somot, Samuel

    2010-10-01

    We assess the impact of two sources of uncertainties in a limited area model (LAM) on the representation of intense precipitation: the size of the domain of integration and the use of the spectral nudging technique (driving of the large-scale within the domain of integration). We work in a perfect-model approach where the LAM is driven by a general circulation model (GCM) run at the same resolution and sharing the same physics and dynamics as the LAM. A set of three 50 km resolution simulations run over Western Europe with the LAM ALADIN-Climate and the GCM ARPEGE-Climate are performed to address this issue. Results are consistent with previous studies regarding the seasonal-mean fields. Furthermore, they show that neither the use of the spectral nudging nor the choice of a small domain are detrimental to the modelling of heavy precipitation in the present experiment.

  14. The magnetic domain structures of Fe thin films on rectangular land-and-groove substrates studied by spin-polarized secondary electron microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Ueda, S. [Photodynamics Research Center, RIKEN, Aoba-ku, Sendai 980-0845 (Japan)]. E-mail: uedas@postman.riken.go.jp; Iwasaki, Y. [Photodynamics Research Center, RIKEN, Aoba-ku, Sendai 980-0845 (Japan); Micro Systems Network Company, Sony Corporation, Tagajo, Miyagi 985-0842 (Japan); Ushioda, S. [Photodynamics Research Center, RIKEN, Aoba-ku, Sendai 980-0845 (Japan); Research Institute of Electrical Communication, Tohoku University, Aoba-ku, Sendai 980-8577 (Japan)

    2004-10-01

    The magnetic domain structures of Fe thin films on rectangular land-and-groove structures have been studied by spin-polarized secondary electron microscopy (SP-SEM) under an applied dc field. The coercive force on the land area was found to be higher than that on the groove area in the magnetization reversal due to the difference in surface roughness between land and groove areas. The magnetic domain structure and domain wall pinning behavior during the reversal process depended on the direction of the magnetic field relative to the rectangles. These results show that the anisotropy induced by film geometry also contributes to the magnetization reversal process of thin magnetic films on land{sub a}nd{sub g}roove substrates.

  15. Purification, isolation, crystallization, and preliminary X-ray diffraction study of the BTB domain of the centrosomal protein 190 from Drosophila melanogaster

    Science.gov (United States)

    Boyko, K. M.; Nikolaeva, A. Yu.; Kachalova, G. S.; Bonchuk, A. N.; Popov, V. O.

    2017-11-01

    The spatial organization of the genome is controlled by a special class of architectural proteins, including proteins containing BTB domains that are able to dimerize or multimerize. The centrosomal protein 190 is one of such architectural proteins. The purification, crystallization, and preliminary X-ray diffraction study of the BTB domain of the centrosomal protein 190 are reported. The crystallization conditions were found by the vapor-diffusion technique. The crystals diffracted to 1.5 Å resolution and belonged to sp. gr. P3221. The structure was solved by the molecular replacement method. The structure refinement is currently underway.

  16. A low energy electron microscopy study of the initial growth, structure, and thermal stability of 4,4'-biphenyldicarboxylic acid domains on Cu(001)

    International Nuclear Information System (INIS)

    Khokhar, Fawad S.; Gastel, Raoul van; Schwarz, Daniel; Zandvliet, Harold J. W.; Poelsema, Bene

    2011-01-01

    The growth of 4,4 ' -biphenyldicarboxylic acid (BDA) on Cu(001) has been studied using low energy electron microscopy and selective area low energy electron diffraction. The emergence of large islands and hydrogen bonding to perpendicularly oriented, adjacent molecules is confirmed. The two benzene rings of adsorbed BDA are twisted along the molecular axis. Unconventional growth of the domains, followed by a second nucleation stage, is observed at room temperature. This unanticipated feature is attributed to the accumulation of stress in the islands. Ostwald ripening in the films and the decay of BDA domains at 448 K exhibits features that are consistent with diffusion limited behavior.

  17. A low energy electron microscopy study of the initial growth, structure, and thermal stability of 4,4{sup '}-biphenyldicarboxylic acid domains on Cu(001)

    Energy Technology Data Exchange (ETDEWEB)

    Khokhar, Fawad S.; Gastel, Raoul van; Schwarz, Daniel; Zandvliet, Harold J. W.; Poelsema, Bene [Physics of Interfaces and Nanomaterials, MESA Institute for Nanotechnology, University of Twente, P.O. Box 217, NL-7500AE Enschede (Netherlands)

    2011-09-28

    The growth of 4,4{sup '}-biphenyldicarboxylic acid (BDA) on Cu(001) has been studied using low energy electron microscopy and selective area low energy electron diffraction. The emergence of large islands and hydrogen bonding to perpendicularly oriented, adjacent molecules is confirmed. The two benzene rings of adsorbed BDA are twisted along the molecular axis. Unconventional growth of the domains, followed by a second nucleation stage, is observed at room temperature. This unanticipated feature is attributed to the accumulation of stress in the islands. Ostwald ripening in the films and the decay of BDA domains at 448 K exhibits features that are consistent with diffusion limited behavior.

  18. Study of physical and chemical properties of Y-Ba-Cu-O ceramic specimens treated with temperature-electric domains for the texture formation

    International Nuclear Information System (INIS)

    Khirnyj, V.F.; Seminozhenko, V.P.; Zagoskin, V.T.

    1995-01-01

    Study of temperature-electric domain (TED) behaviour is conducted and physico-chemical properties of specimens treated by moving TED are investigated. According to the data obtained, texture does not appear during such a treatment. To reduce v of TED the specimen is placed to a longitudinal magnetic field. TED stop at H=0.4 T and V=3.2 V is observed when the direction of the north magnetic pole coincides with the point of the positive electrode junction. Domain movement rate, at which texture occurrence is possible, is achieved by means of magnetic field intensity H variation. 10 refs.; 3 figs.; 1 tab

  19. Quantum Mechanics and Molecular Mechanics Study of the Catalytic Mechanism of Human AMSH-LP Domain Deubiquitinating Enzymes.

    Science.gov (United States)

    Zhu, Wenyou; Liu, Yongjun; Ling, Baoping

    2015-08-25

    Deubiquitinating enzymes (DUBs) catalyze the cleavage of the isopeptide bond in polyubiquitin chains to control and regulate the deubiquitination process in all known eukaryotic cells. The human AMSH-LP DUB domain specifically cleaves the isopeptide bonds in the Lys63-linked polyubiquitin chains. In this article, the catalytic mechanism of AMSH-LP has been studied using a combined quantum mechanics and molecular mechanics method. Two possible hydrolysis processes (Path 1 and Path 2) have been considered. Our calculation results reveal that the activation of Zn(2+)-coordinated water molecule is the essential step for the hydrolysis of isopeptide bond. In Path 1, the generated hydroxyl first attacks the carbonyl group of Gly76, and then the amino group of Lys63 is protonated, which is calculated to be the rate limiting step with an energy barrier of 13.1 kcal/mol. The energy barrier of the rate limiting step and the structures of intermediate and product are in agreement with the experimental results. In Path 2, the protonation of amino group of Lys63 is prior to the nucleophilic attack of activated hydroxyl. The two proton transfer processes in Path 2 correspond to comparable overall barriers (33.4 and 36.1 kcal/mol), which are very high for an enzymatic reaction. Thus, Path 2 can be ruled out. During the reaction, Glu292 acts as a proton transfer mediator, and Ser357 mainly plays a role in stabilizing the negative charge of Gly76. Besides acting as a Lewis acid, Zn(2+) also influences the reaction by coordinating to the reaction substrates (W1 and Gly76).

  20. Improving the performance of DomainDiscovery of protein domain boundary assignment using inter-domain linker index

    Directory of Open Access Journals (Sweden)

    Zomaya Albert Y

    2006-12-01

    Full Text Available Abstract Background Knowledge of protein domain boundaries is critical for the characterisation and understanding of protein function. The ability to identify domains without the knowledge of the structure – by using sequence information only – is an essential step in many types of protein analyses. In this present study, we demonstrate that the performance of DomainDiscovery is improved significantly by including the inter-domain linker index value for domain identification from sequence-based information. Improved DomainDiscovery uses a Support Vector Machine (SVM approach and a unique training dataset built on the principle of consensus among experts in defining domains in protein structure. The SVM was trained using a PSSM (Position Specific Scoring Matrix, secondary structure, solvent accessibility information and inter-domain linker index to detect possible domain boundaries for a target sequence. Results Improved DomainDiscovery is compared with other methods by benchmarking against a structurally non-redundant dataset and also CASP5 targets. Improved DomainDiscovery achieves 70% accuracy for domain boundary identification in multi-domains proteins. Conclusion Improved DomainDiscovery compares favourably to the performance of other methods and excels in the identification of domain boundaries for multi-domain proteins as a result of introducing support vector machine with benchmark_2 dataset.

  1. Using theory to explore facilitators and barriers to delayed prescribing in Australia: a qualitative study using the Theoretical Domains Framework and the Behaviour Change Wheel.

    Science.gov (United States)

    Sargent, Lucy; McCullough, Amanda; Del Mar, Chris; Lowe, John

    2017-02-13

    Delayed antibiotic prescribing reduces antibiotic use for acute respiratory infections in trials in general practice, but the uptake in clinical practice is low. The aim of the study was to identify facilitators and barriers to general practitioners' (GPs') use of delayed prescribing and to gain pharmacists' and the public's views about delayed prescribing in Australia. This study used the Theoretical Domains Framework and the Behaviour Change Wheel to explore facilitators and barriers to delayed prescribing in Australia. Forty-three semi-structured, face-to-face interviews with general practitioners, pharmacists and patients were conducted. Responses were coded into domains of the Theoretical Domains Framework, and specific criteria from the Behaviour Change Wheel were used to identify which domains were relevant to increasing the use of delayed prescribing by GPs. The interviews revealed nine key domains that influence GPs' use of delayed prescribing: knowledge; cognitive and interpersonal skills; memory, attention and decision-making processes; optimism; beliefs about consequences; intentions; goals; emotion; and social influences: GPs knew about delayed prescribing; however, they did not use it consistently, preferring to bring patients back for review and only using it with patients in a highly selective way. Pharmacists would support GPs and the public in delayed prescribing but would fill the prescription if people insisted. The public said they would delay taking their antibiotics if asked by their GP and given the right information on managing symptoms and when to take antibiotics. Using a theory-driven approach, we identified nine key domains that influence GPs' willingness to provide a delayed prescription to patients with an acute respiratory infection presenting to general practice. These data can be used to develop a structured intervention to change this behaviour and thus reduce antibiotic use for acute respiratory infections in general practice.

  2. Towards a Differentiated and Domain-Specific View of Educational Technology: An Exploratory Study of History Teachers' Technology Use

    Science.gov (United States)

    Voet, Michiel; De Wever, Bram

    2017-01-01

    Adopting a differentiated and domain-specific view of educational technology, the present study focuses on the case of school history. It argues that, in this particular context, one of technology's main assets is its ability to support inquiry-based learning activities, during which students interpret the past through historical reasoning. As…

  3. Needed Research on Child Socialization. A Special Report of the USOE-Sponsored Grant Study: Critical Appraisal of Research in the Personality-Emotions-Motivation Domain.

    Science.gov (United States)

    Gorsuch, Richard L.; And Others

    The task group report presented in this publication is one of a series prepared by eminent psychologists who have served as consultants in the U.S. Office of Education-sponsored grant study to conduct a Critical Appraisal of the Personality-Emotions-Motivation Domain. In order to achieve the goal of identifying important problems and areas for new…

  4. Heuristic Chemistry--A Qualitative Study on Teaching Domain-Specific Strategies for the Six-Electron Case

    Science.gov (United States)

    Graulich, Nicole; Tiemann, Rudiger; Schreiner, Peter R.

    2012-01-01

    We investigate the efficiency of domain-specific heuristic strategies in mastering and predicting pericyclic six-electron rearrangements. Based on recent research findings on these types of reactions a new concept has been developed that should help students identify and describe six-electron rearrangements more readily in complex molecules. The…

  5. The PAS fold: A redefinition of the PAS domain based upon structural prediction. A large-scale homology modelling study

    NARCIS (Netherlands)

    Hefti, M.H.; Francoijs, C.J.J.; Vries, de S.C.; Dixon, R.; Vervoort, J.J.M.

    2004-01-01

    In the postgenomic era it is essential that protein sequences are annotated correctly in order to help in the assignment of their putative functions. Over 1300 proteins in current protein sequence databases are predicted to contain a PAS domain based upon amino acid sequence alignments. One of the

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

    NARCIS (Netherlands)

    Bird, L.E.; Ren, J.; Nettleship, J.E.; Folkers, G.E.|info:eu-repo/dai/nl/162277202; Owens, RJ; Stammers, D.K.

    2010-01-01

    Zhx1 to 3 (zinc-fingers and homeoboxes) form a set of paralogous genes encoding multi-domain proteins. ZHX proteins consist of two zinc fingers followed by five homeodomains. ZHXs have biological roles in cell cycle control by acting as co-repressors of the transcriptional regulator Nuclear Factor

  7. Topological domain walls in helimagnets

    Science.gov (United States)

    Schoenherr, P.; Müller, J.; Köhler, L.; Rosch, A.; Kanazawa, N.; Tokura, Y.; Garst, M.; Meier, D.

    2018-05-01

    Domain walls naturally arise whenever a symmetry is spontaneously broken. They interconnect regions with different realizations of the broken symmetry, promoting structure formation from cosmological length scales to the atomic level1,2. In ferroelectric and ferromagnetic materials, domain walls with unique functionalities emerge, holding great promise for nanoelectronics and spintronics applications3-5. These walls are usually of Ising, Bloch or Néel type and separate homogeneously ordered domains. Here we demonstrate that a wide variety of new domain walls occurs in the presence of spatially modulated domain states. Using magnetic force microscopy and micromagnetic simulations, we show three fundamental classes of domain walls to arise in the near-room-temperature helimagnet iron germanium. In contrast to conventional ferroics, the domain walls exhibit a well-defined inner structure, which—analogous to cholesteric liquid crystals—consists of topological disclination and dislocation defects. Similar to the magnetic skyrmions that form in the same material6,7, the domain walls can carry a finite topological charge, permitting an efficient coupling to spin currents and contributions to a topological Hall effect. Our study establishes a new family of magnetic nano-objects with non-trivial topology, opening the door to innovative device concepts based on helimagnetic domain walls.

  8. Aerosol modelling for regional climate studies: application to anthropogenic particles and evaluation over a European/African domain

    International Nuclear Information System (INIS)

    Solmon, F.; Giorgi, F.; Liousse, C.

    2006-01-01

    A simplified anthropogenic aerosol model for use in climate studies is developed and implemented within the regional climate model RegCM. The model includes sulphur dioxide, sulphate, hydrophobic and hydrophilic black carbon (BC) and organic carbon (OC) and is run for the winter and summer seasons of 2000 over a large domain extending from northern Europe to south tropical Africa. An evaluation of the model performance is carried out in terms of surface concentrations and aerosol optical depths (AODs). For sulphur dioxide and sulphate concentration, comparison of simulated fields and experimental data collected over the EMEP European network shows that the model generally reproduces the observed spatial patterns of near-surface sulphate. Sulphate concentrations are within a factor of 2 of observations in 34% (JJA) to 57% (DJF) of cases. For OC and BC, simulated concentrations are compared to different datasets. The simulated and observed values agree within a factor of 2 in 56% (DJF) to 62% (JJA) of cases for BC and 33% (JJA) to 64% (DJF) for OC. Simulated AODs are compared with ground-based (AERONET) and satellite (MODIS, MISR, TOMS) AOD datasets. Simulated AODs are in the range of AERONET and MISR data over northern Europe, and AOD spatial patterns show consistency with MODIS and TOMS retrievals both over Europe and Africa. The main model deficiencies we find are: (i) an underestimation of surface concentrations of sulphate and OC during the summer and especially over the Mediterranean region and (ii) a general underestimation of AOD, most pronounced over the Mediterranean basin. The primary factors we identify as contributing to these biases are the lack of natural aerosols (in particular, desert dust, secondary biogenic aerosols and nitrates), uncertainties in the emission inventories and aerosol cycling by moist convection. Also, in view of the availability of better observing datasets (e.g. as part of the AMMA project), we are currently working on improving

  9. CARF and WYL domains: ligand-binding regulators of prokaryotic defense systems

    Directory of Open Access Journals (Sweden)

    Kira eMakarova

    2014-04-01

    Full Text Available CRISPR-Cas adaptive immunity systems of bacteria and archaea insert fragments of virus or plasmid DNA as spacer sequences into CRISPR repeat loci. Processed transcripts encompassing these spacers guide the cleavage of the cognate foreign DNA or RNA. Most CRISPR-Cas loci, in addition to recognized cas genes, also include genes that are not directly implicated in spacer acquisition, CRISPR transcript processing or interference. Here we comprehensively analyze sequences, structures and genomic neighborhoods of one of the most widespread groups of such genes that encode proteins containing a predicted nucleotide-binding domain with a Rossmann-like fold, which we denote CARF (CRISPR-associated Rossmann fold. Several CARF protein structures have been determined but functional characterization of these proteins is lacking. The CARF domain is most frequently combined with a C-terminal winged helix-turn-helix DNA-binding domain and effector domains most of which are predicted to possess DNase or RNase activity. Divergent CARF domains are also found in RtcR proteins, sigma-54 dependent regulators of the rtc RNA repair operon. CARF genes frequently co-occur with those coding for proteins containing the WYL domain with the Sm-like SH3 β-barrel fold, which is also predicted to bind ligands. CRISPR-Cas and possibly other defense systems are predicted to be transcriptionally regulated by multiple ligand-binding proteins containing WYL and CARF domains which sense modified nucleotides and nucleotide derivatives generated during virus infection. We hypothesize that CARF domains also transmit the signal from the bound ligand to the fused effector domains which attack either alien or self nucleic acids, resulting, respectively, in immunity complementing the CRISPR-Cas action or in dormancy/programmed cell death.

  10. The four-domain structure model of a depression scale for medical students: A cross-sectional study in Haiphong, Vietnam.

    Science.gov (United States)

    Nguyen, Thao Thi Thu; Nguyen, Ngoc Thi Minh; Pham, Manh Van; Pham, Han Van; Nakamura, Hiroyuki

    2018-01-01

    Depression is a common mental health problem with a higher prevalence in medical students than in the general population. This study aims to investigate the association between depressive symptoms, particularly those in each domain of the Center for Epidemiological Studies Depression (CES-D) Scale, and related factors. A cross-sectional study was conducted with a random sample of 1319 medical students at Haiphong University of Medicine and Pharmacy in 2016. The CES-D scale and a self-reported questionnaire were used to identify the prevalence of depressive symptoms and related risk factors. Univariate and multivariate logistic regression were performed to assess the risk factors associated with depressive symptoms and the score for each structure factor. Depressive symptoms were observed in 514 (39%) students, including more males than females (44.2% vs 36.9%, p = 0.015). Students whose mothers' highest education level was primary school had a higher prevalence of depressive symptoms than students whose mothers had higher education levels (p = 0.038). There was a significant relationship between depressive symptoms and stressful life events, especially a decline in personal health. A higher correlation was found between the somatic complaints and depressive affect domains. The impacts of risk factors differed for each domain of the depression scale. Only the factor of achieving excellence showed no statistically significant associations with depressive symptoms and the scores on the four domains considered in this study. The high prevalence of depressive symptoms among medical students with risk factors and the impact of these risk factors on each domain of depression scale need further clarification to alleviate depression in students during their medical training.

  11. A qualitative study using the Theoretical Domains Framework to investigate why patients were or were not assessed for rehabilitation after stroke.

    Science.gov (United States)

    Lynch, Elizabeth A; Luker, Julie A; Cadilhac, Dominique A; Fryer, Caroline E; Hillier, Susan L

    2017-07-01

    To explore the factors perceived to affect rehabilitation assessment and referral practices for patients with stroke. Qualitative study using data from focus groups analysed thematically and then mapped to the Theoretical Domains Framework. Eight acute stroke units in two states of Australia. Health professionals working in acute stroke units. Health professionals at all sites had participated in interventions to improve rehabilitation assessment and referral practices, which included provision of copies of an evidence-based decision-making rehabilitation Assessment Tool and pathway. Eight focus groups were conducted (32 total participants). Reported rehabilitation assessment and referral practices varied markedly between units. Continence and mood were not routinely assessed (4 units), and people with stroke symptoms were not consistently referred to rehabilitation (4 units). Key factors influencing practice were identified and included whether health professionals perceived that use of the Assessment Tool would improve rehabilitation assessment practices (theoretical domain 'social and professional role'); beliefs about outcomes from changing practice such as increased equity for patients or conversely that changing rehabilitation referral patterns would not affect access to rehabilitation ('belief about consequences'); the influence of the unit's relationships with other groups including rehabilitation teams ('social influences' domain) and understanding within the acute stroke unit team of the purpose of changing assessment practices ('knowledge' domain). This study has identified that health professionals' perceived roles, beliefs about consequences from changing practice and relationships with rehabilitation service providers were perceived to influence rehabilitation assessment and referral practices on Australian acute stroke units.

  12. Patterns of physical activity in different domains and implications for intervention in a multi-ethnic Asian population: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Tai E Shyong

    2010-10-01

    Full Text Available Abstract Background The benefits of regular physical activity for quality of life and disease prevention have been well documented. Identification of low activity groups would facilitate interventional programs. Many studies have focussed on leisure time activity, which may not capture the spectrum of physical activity relevant to disease prevention. Furthermore, few studies have been conducted in urban Asian settings. Methods We evaluated physical activity in different domains (leisure time, occupational, household and transportation and its sociodemographic determinants in 4750 adult Chinese, Malay, and Asian Indian Singaporeans. Physical activity was assessed using locally validated questionnaires. Results Occupational and household activity contributed substantially more to total physical activity than leisure time or transportation activity. However, when only activity of at least moderate intensity was considered leisure time activity contributed most to total physical activity. Higher socio-economic status was associated with more leisure time activity, but less total physical activity due to reduced activity in the other domains. Chinese ethnicity was also associated with less total physical activity as a result of less activity in non-leisure time domains. Conclusions In assessing levels of physical activity and recommending changes, it is important to consider physical activity in different domains. Focus on leisure-time physical activity alone could identify the wrong groups for intervention and miss opportunities for increasing physical activity in populations.

  13. Investigating the use of terahertz pulsed time domain reflection imaging for the study of fabric layers of an Egyptian mummy

    Science.gov (United States)

    Fukunaga, K.; Cortes, E.; Cosentino, A.; Stã¼nkel, I.; Leona, M.; Duling, N.; Mininberg, D. T.

    2011-08-01

    This paper reports the first use of terahertz time domain reflection imaging involving textiles on part of a complete human mummy, still in original wrapping. X-ray technique has been used extensively to investigate anatomical features, since X-ray pass through the wrapping. Terahertz waves, on the other hand, can penetrate into non-metallic materials and its reflection depends on the refractive index of materials at the interface, such as textiles and the air. The mummy of Kharushere (ca. 945-712 B.C.) was examined by using Terahertz time domain reflection imaging in the Egyptian galleries of The Metropolitan Museum of Art. Experimental results suggest that the Terahetz imaging is a promising technique for probing the fabric layers surrounding Egyptian mummies, although it is still very limited in its current state. In the future it could become a useful complement to CT scanning when materials with low radiographic density and contrast are being investigated

  14. Achieving behaviour change for detection of Lynch syndrome using the Theoretical Domains Framework Implementation (TDFI) approach: a study protocol.

    Science.gov (United States)

    Taylor, Natalie; Long, Janet C; Debono, Deborah; Williams, Rachel; Salisbury, Elizabeth; O'Neill, Sharron; Eykman, Elizabeth; Braithwaite, Jeffrey; Chin, Melvin

    2016-03-12

    Lynch syndrome is an inherited disorder associated with a range of cancers, and found in 2-5 % of colorectal cancers. Lynch syndrome is diagnosed through a combination of significant family and clinical history and pathology. The definitive diagnostic germline test requires formal patient consent after genetic counselling. If diagnosed early, carriers of Lynch syndrome can undergo increased surveillance for cancers, which in turn can prevent late stage cancers, optimise treatment and decrease mortality for themselves and their relatives. However, over the past decade, international studies have reported that only a small proportion of individuals with suspected Lynch syndrome were referred for genetic consultation and possible genetic testing. The aim of this project is to use behaviour change theory and implementation science approaches to increase the number and speed of healthcare professional referrals of colorectal cancer patients with a high-likelihood risk of Lynch syndrome to appropriate genetic counselling services. The six-step Theoretical Domains Framework Implementation (TDFI) approach will be used at two large, metropolitan hospitals treating colorectal cancer patients. Steps are: 1) form local multidisciplinary teams to map current referral processes; 2) identify target behaviours that may lead to increased referrals using discussion supported by a retrospective audit; 3) identify barriers to those behaviours using the validated Influences on Patient Safety Behaviours Questionnaire and TDFI guided focus groups; 4) co-design interventions to address barriers using focus groups; 5) co-implement interventions; and 6) evaluate intervention impact. Chi square analysis will be used to test the difference in the proportion of high-likelihood risk Lynch syndrome patients being referred for genetic testing before and after intervention implementation. A paired t-test will be used to assess the mean time from the pathology test results to referral for high

  15. Structural studies of the yeast DNA damage-inducible protein Ddi1 reveal domain architecture of this eukaryotic protein family

    Czech Academy of Sciences Publication Activity Database

    Trempe, J. F.; Grantz Šašková, Klára; Sivá, Monika; Ratcliffe, C. D. H.; Veverka, Václav; Hoegl, A.; Ménade, M.; Feng, X.; Shenker, S.; Svoboda, Michal; Kožíšek, Milan; Konvalinka, Jan; Gehring, K.

    2016-01-01

    Roč. 6, Sep 20 (2016), č. článku 33671. ISSN 2045-2322 R&D Projects: GA MŠk(CZ) LK11205; GA MŠk(CZ) LO1304 Institutional support: RVO:61388963 Keywords : ubiquitin-associated domains * ray solution scattering * torsion angle dynamics Subject RIV: CE - Biochemistry Impact factor: 4.259, year: 2016 http://www.nature.com/articles/srep33671

  16. Study on k-shortest paths with behavioral impedance domain from the intermodal public transportation system perspective

    OpenAIRE

    Pereira, Hernane Borges de Barros; Pérez Vidal, Lluís; Lozada, Eleazar G. Madrid

    2003-01-01

    Behavioral impedance domain consists of a theory on route planning for pedestrians, within which constraint management is considered. The goal of this paper is to present the k-shortest path model using the behavioral impedance approach. After the mathematical model building, optimization problem and resolution problem by a behavioral impedance algorithm, it is discussed how behavioral impedance cost function is embedded in the k-shortest path model. From the pedestrian's route planning persp...

  17. DNA Recognition by the DNA Primase of Bacteriophage T7: A Structure Function Study of the Zinc-Binding Domain

    International Nuclear Information System (INIS)

    Akabayov, B.; Lee, S.; Akabayov, S.; Rekhi, S.; Zhu, B.; Richardson, C.

    2009-01-01

    Synthesis of oligoribonucleotide primers for lagging-strand DNA synthesis in the DNA replication system of bacteriophage T7 is catalyzed by the primase domain of the gene 4 helicase-primase. The primase consists of a zinc-binding domain (ZBD) and an RNA polymerase (RPD) domain. The ZBD is responsible for recognition of a specific sequence in the ssDNA template whereas catalytic activity resides in the RPD. The ZBD contains a zinc ion coordinated with four cysteine residues. We have examined the ligation state of the zinc ion by X-ray absorption spectroscopy and biochemical analysis of genetically altered primases. The ZBD of primase engaged in catalysis exhibits considerable asymmetry in coordination to zinc, as evidenced by a gradual increase in electron density of the zinc together with elongation of the zinc-sulfur bonds. Both wild-type primase and primase reconstituted from purified ZBD and RPD have a similar electronic change in the level of the zinc ion as well as the configuration of the ZBD. Single amino acid replacements in the ZBD (H33A and C36S) result in the loss of both zinc binding and its structural integrity. Thus the zinc in the ZBD may act as a charge modulation indicator for the surrounding sulfur atoms necessary for recognition of specific DNA sequences.

  18. Same but not alike: Structure, flexibility and energetics of domains in multi-domain proteins are influenced by the presence of other domains.

    Science.gov (United States)

    Vishwanath, Sneha; de Brevern, Alexandre G; Srinivasan, Narayanaswamy

    2018-02-01

    The majority of the proteins encoded in the genomes of eukaryotes contain more than one domain. Reasons for high prevalence of multi-domain proteins in various organisms have been attributed to higher stability and functional and folding advantages over single-domain proteins. Despite these advantages, many proteins are composed of only one domain while their homologous domains are part of multi-domain proteins. In the study presented here, differences in the properties of protein domains in single-domain and multi-domain systems and their influence on functions are discussed. We studied 20 pairs of identical protein domains, which were crystallized in two forms (a) tethered to other proteins domains and (b) tethered to fewer protein domains than (a) or not tethered to any protein domain. Results suggest that tethering of domains in multi-domain proteins influences the structural, dynamic and energetic properties of the constituent protein domains. 50% of the protein domain pairs show significant structural deviations while 90% of the protein domain pairs show differences in dynamics and 12% of the residues show differences in the energetics. To gain further insights on the influence of tethering on the function of the domains, 4 pairs of homologous protein domains, where one of them is a full-length single-domain protein and the other protein domain is a part of a multi-domain protein, were studied. Analyses showed that identical and structurally equivalent functional residues show differential dynamics in homologous protein domains; though comparable dynamics between in-silico generated chimera protein and multi-domain proteins were observed. From these observations, the differences observed in the functions of homologous proteins could be attributed to the presence of tethered domain. Overall, we conclude that tethered domains in multi-domain proteins not only provide stability or folding advantages but also influence pathways resulting in differences in

  19. Magnetic domain-wall motion study under an electric field in a Finemet{sup ®} thin film on flexible substrate

    Energy Technology Data Exchange (ETDEWEB)

    Lan, Ngo Thi [Laboratoire des Sciences des Procédés et des Matériaux, CNRS-Université Paris XIII, 93430 Villetaneuse (France); Mercone, Silvana, E-mail: silvana.mercone@univ-paris13.fr [Laboratoire des Sciences des Procédés et des Matériaux, CNRS-Université Paris XIII, 93430 Villetaneuse (France); Moulin, Johan [Institut d' Electronique Fondamentale, UMR 8622 Université Paris Sud/CNRS, Orsay (France); Bahoui, Anouar El; Faurie, Damien; Zighem, Fatih; Belmeguenai, Mohamed; Haddadi, Halim [Laboratoire des Sciences des Procédés et des Matériaux, CNRS-Université Paris XIII, 93430 Villetaneuse (France)

    2015-01-01

    We study the influence of applied in-plane elastic strains on the static magnetic configuration of a 530 nm magnetostrictive FeCuNbSiB (Finemet{sup ®}) thin film. The in-plane strains are induced via the application of a voltage to a piezoelectric actuator on which the film/substrate system was glued. A quantitative characterization of the voltage dependence of the induced-strain at the surface of the film was performed using a digital image correlation technique. Magnetic Force Microscopy (MFM) images at remanence (H=0 Oe and U=0 V) clearly reveal the presence of weak stripe domains. The effect of the voltage-induced strain shows the existence of a voltage threshold value for the strike configuration break. For a maximum strain of ε{sub XX}∼0.5×10{sup −3} we succeed in destabilizing the stripes configuration helping the setting up of a complete homogeneous magnetic pattern. - Highlights: • Elastic strain effect on the magnetic domain structure of a Finemet/Kapton is investigated. • External loading is applied thanks to a piezo-actuator on which the sample is glued. • The amount of strains was measured by the Digital Image Correlation technique. • Magnetic Force Microscopy showed high mobility of magnetic stripes domains. • Bending, curving and branching of domains go into maze-like pattern.

  20. Texture of lipid bilayer domains

    DEFF Research Database (Denmark)

    Jensen, Uffe Bernchou; Brewer, Jonathan R.; Midtiby, Henrik Skov

    2009-01-01

    We investigate the texture of gel (g) domains in binary lipid membranes composed of the phospholipids DPPC and DOPC. Lateral organization of lipid bilayer membranes is a topic of fundamental and biological importance. Whereas questions related to size and composition of fluid membrane domain...... are well studied, the possibility of texture in gel domains has so far not been examined. When using polarized light for two-photon excitation of the fluorescent lipid probe Laurdan, the emission intensity is highly sensitive to the angle between the polarization and the tilt orientation of lipid acyl...... chains. By imaging the intensity variations as a function of the polarization angle, we map the lateral variations of the lipid tilt within domains. Results reveal that gel domains are composed of subdomains with different lipid tilt directions. We have applied a Fourier decomposition method...

  1. Possible Influences on the Interpretation of Functional Domain (FD) Near-Infrared Spectroscopy (NIRS): An Explorative Study.

    Science.gov (United States)

    Celie, Bert M; Boone, Jan; Dumortier, Jasmien; Derave, Wim; De Backer, Tine; Bourgois, Jan G

    2016-02-01

    The influence of subcutaneous adipose tissue (ATT) and oxygen (O2) delivery has been poorly defined in frequency domain (FD) near-infrared spectroscopy (NIRS). Therefore, the aim of this study was to investigate the possible influence of these variables on all FD NIRS responses using a reliable protocol. Moreover, these influences were also investigated when using relative oxy- and deoxyhemoglobin and -myoglobin (oxy[Hb + Mb] and deoxy[Hb + Mb]) values (in %). A regression analysis was carried out for ATT and maximal-minimum oxy[Hb + Mb], deoxy[Hb + Mb], oxygen saturation (SmO2), and total hemoglobin (totHb) amplitudes during an incremental cyclic contraction protocol (ICCP) in a group of 45 participants. Moreover, the same analysis was carried out between subcutaneous ATT and the relative oxy- and deoxy[Hb + Mb] values (in %). In the second part of this study, a regression analysis was performed for peak forearm blood flow (FBF) during ICCP and the absolute and relative NIRS values in a group of 37 participants. Significant exponential correlation coefficients were found between ATT and deoxy[Hb + Mb] (r = 0.53; P < 0.001), oxy[Hb + Mb] (r = 0.57; P < 0.001), and SmO2 amplitudes (r = 0.57; P < 0.001). No significant relations were found between ATT and relative oxy[Hb + Mb] (r = 0.37; P = 0.07) and deoxy[Hb + Mb] (r = 0.09; P = 0.82). Significant positive correlation coefficients were found between force at exhaustion and maximal FBF (r = 0.66; P < 0.001), maximal differences in deoxy[Hb + Mb] (r = 0.353; P = 0.032) and totHb (r = 0.512; P = 0.002) while no significant correlation coefficients were found between these maximal force values and maximal differences in oxy[Hb + Mb] (r = -0.267; P = 0.111) and SmO2 (r = -0.267; P = 0.111). Significant linear correlation coefficients were found between FBF and deoxy[Hb + Mb] (r = 0.51; P

  2. Heteronuclear multidimensional NMR and homology modelling studies of the C-terminal nucleotide-binding domain of the human mitochondrial ABC transporter ABCB6

    Energy Technology Data Exchange (ETDEWEB)

    Kurashima-Ito, Kaori [RIKEN, Cellular and Molecular Biology Laboratory (Japan); Ikeya, Teppei [National Institute of Advanced Industrial Science and Technology (AIST), (Japan); Senbongi, Hiroshi [Mitochondrial Diseases Group, MRC Dunn Human NutritionUnit (United Kingdom); Tochio, Hidehito [International Graduate School of Arts and Sciences, Supramolecular Biology, Yokohama City University, Molecular Biophysics Laboratory (Japan); Mikawa, Tsutomu [RIKEN, Cellular and Molecular Biology Laboratory (Japan); Shibata, Takehiko [RIKEN, Shibata Distinguished Senior Scientist Laboratory (Japan); Ito, Yutaka [RIKEN, Cellular and Molecular Biology Laboratory (Japan)], E-mail: ito-yutaka@center.tmu.ac.jp

    2006-05-15

    Human ATP-binding cassette, sub-family B, member 6 (ABCB6) is a mitochondrial ABC transporter, and presumably contributes to iron homeostasis. Aimed at understanding the structural basis for the conformational changes accompanying the substrate-transportation cycle, we have studied the C-terminal nucleotide-binding domain of ABCB6 (ABCB6-C) in both the nucleotide-free and ADP-bound states by heteronuclear multidimensional NMR and homology modelling. A non-linear sampling scheme was utilised for indirectly acquired {sup 13}C and {sup 15}N dimensions of all 3D triple-resonance NMR experiments, in order to overcome the instability and the low solubility of ABCB6-C. The backbone resonances for approximately 25% of non-proline residues, which are mostly distributed around the functionally important loops and in the Helical domain, were not observed for nucleotide-free form of ABCB6-C. From the pH, temperature and magnetic field strength dependencies of the resonance intensities, we concluded that this incompleteness in the assignments is mainly due to the exchange between multiple conformations at an intermediate rate on the NMR timescale. These localised conformational dynamics remained in ADP-bound ABCB6-C except for the loops responsible for adenine base and {alpha}/{beta}-phosphate binding. These results revealed that the localised dynamic cooperativity, which was recently proposed for a prokaryotic ABC MJ1267, also exists in a higher eukaryotic ABC, and is presumably shared by all members of the ABC family. Since the Helical domain is the putative interface to the transmembrane domain, this cooperativity may explain the coupled functions between domains in the substrate-transportation cycle.

  3. Studying behavior of multilayer materials: A 1-D model correlated to magnetic domain walls through complex permeability

    International Nuclear Information System (INIS)

    Ahmadi, B.; Chazal, H.; Waeckerle, T.; Roudet, J.

    2008-01-01

    Multilayer cores are suitable for integrated planar magnetic components. We proposed here to investigate the frequency behavior of multilayer nanocrystalline cores in the frame of a one-dimensional (1-D) electromagnetic propagation model. Electromagnetic wave equations are considered to explain the phenomena from the macroscopic point of view. A domain wall description is considered to take into account non-homogeneity of magnetic media. This mesoscopic model is correlated to macroscopic model through complex permeability. The scope of validity of the model is determined by means of indirect permeability measurement. Finally, the behavior of the multilayer core is predicted by using an equivalent electrical circuit and will interest component designers

  4. Cognitive flexibility in verbal and nonverbal domains and decision making in anorexia nervosa patients: a pilot study

    Directory of Open Access Journals (Sweden)

    Marzola Enrica

    2011-10-01

    Full Text Available Abstract Background This paper aimed to investigate cognitive rigidity and decision making impairments in patients diagnosed with Anorexia Nervosa Restrictive type (AN-R, assessing also verbal components. Methods Thirty patients with AN-R were compared with thirty age-matched healthy controls (HC. All participants completed a comprehensive neuropsychological battery comprised of the Trail Making Test, Wisconsin Card Sorting Test, Hayling Sentence Completion Task, and the Iowa Gambling Task. The Beck Depression Inventory was administered to evaluate depressive symptomatology. The influence of both illness duration and neuropsychological variables was considered. Body Mass Index (BMI, years of education, and depression severity were considered as covariates in statistical analyses. Results The AN-R group showed poorer performance on all neuropsychological tests. There was a positive correlation between illness duration and the Hayling Sentence Completion Task Net score, and number of completion answers in part B. There was a partial effect of years of education and BMI on neuropsychological test performance. Response inhibition processes and verbal fluency impairment were not associated with BMI and years of education, but were associated with depression severity. Conclusions These data provide evidence that patients with AN-R have cognitive rigidity in both verbal and non-verbal domains. The role of the impairment on verbal domains should be considered in treatment. Further research is warranted to better understand the relationship between illness state and cognitive rigidity and impaired decision-making.

  5. Expression, crystallization and preliminary crystallographic study of mouse hepatitis virus (MHV) nucleocapsid protein C-terminal domain

    International Nuclear Information System (INIS)

    Tong, Xiaohang; Ma, Yanlin; Li, Xuemei

    2010-01-01

    The C-terminal domain of mouse hepatitis virus nucleocapsid protein has been overexpressed in E. coli, purified and crystallized. The crystal belonged to space group P422, with unit-cell parameters a = 66.6, c = 50.8 Å, and diffracted to 2.20 Å resolution. Mouse hepatitis virus (MHV) belongs to the group II coronaviruses. The virus produces nine genes encoding 11 proteins that could be recognized as structural proteins and nonstructural proteins and are crucial for viral RNA synthesis. The nucleocapsid (N) protein, one of the structural proteins, interacts with the 30.4 kb virus genomic RNA to form the helical nucleocapsid and associates with the membrane glycoprotein via its C-terminus to stabilize virion assembly. Here, the expression and crystallization of the MHV nucleocapsid protein C-terminal domain are reported. The crystals diffracted to 2.20 Å resolution and belonged to space group P422, with unit-cell parameters a = 66.6, c = 50.8 Å. Assuming the presence of two molecules in the asymmetric unit, the solvent content is 43.0% (V M = 2.16 Å 3 Da −1 )

  6. Crystallization and preliminary crystallographic studies of the copper-binding domain of the amyloid precursor protein of Alzheimer’s disease

    Energy Technology Data Exchange (ETDEWEB)

    Kong, Geoffrey K.-W. [Biota Structural Biology Laboratory, St Vincent’s Institute, 9 Princes Street, Fitzroy, Victoria 3065 (Australia); Department of Pathology, The University of Melbourne, Victoria 3010 (Australia); Galatis, Denise; Barnham, Kevin J. [Department of Pathology, The University of Melbourne, Victoria 3010 (Australia); The Mental Health Research Institute of Victoria, Parkville, Victoria 3052 (Australia); Polekhina, Galina; Adams, Julian J. [Biota Structural Biology Laboratory, St Vincent’s Institute, 9 Princes Street, Fitzroy, Victoria 3065 (Australia); Masters, Colin L. [Department of Pathology, The University of Melbourne, Victoria 3010 (Australia); The Mental Health Research Institute of Victoria, Parkville, Victoria 3052 (Australia); Cappai, Roberto [Department of Pathology, The University of Melbourne, Victoria 3010 (Australia); The Mental Health Research Institute of Victoria, Parkville, Victoria 3052 (Australia); Centre for Neuroscience, The University of Melbourne, Victoria 3010 (Australia); Parker, Michael W.; McKinstry, William J., E-mail: wmckinstry@svi.edu.au [Biota Structural Biology Laboratory, St Vincent’s Institute, 9 Princes Street, Fitzroy, Victoria 3065 (Australia)

    2005-01-01

    The binding of Cu{sup 2+} ions to the copper-binding domain of the amyloid precursor protein of Alzheimer’s disease reduces the production of the amyloid β peptide, which is centrally involved in Alzheimer’s disease. Structural studies of the copper-binding domain will provide a basis for structure-based drug design that might prove useful in treating this devastating disease. Alzheimer’s disease is thought to be triggered by production of the amyloid β (Aβ) peptide through proteolytic cleavage of the amyloid precursor protein (APP). The binding of Cu{sup 2+} to the copper-binding domain (CuBD) of APP reduces the production of Aβ in cell-culture and animal studies. It is expected that structural studies of the CuBD will lead to a better understanding of how copper binding causes Aβ depletion and will define a potential drug target. The crystallization of CuBD in two different forms suitable for structure determination is reported here.

  7. Domains of health-related quality of life in age-related macular degeneration: a qualitative study in the Chinese cultural context

    Science.gov (United States)

    Bian, Wei; Wan, Junli; Smith, Graeme; Li, Shiying; Tan, Mingqiong; Zhou, Fengjiao

    2018-01-01

    Objective To explore which areas of health-related quality of life were affected in Chinese patients, and to identify whether the areas are well covered by validated questionnaires. Design A qualitative study based on semistructured interviews was conducted. A qualitative thematic analysis following the approach of Colaizzi was used to analyse the interview data for significant statements and phrases. The themes and subthemes organised from the analysis were then compared by using the following current instruments: National Eye Institute Visual Function Questionnaire (NEI-VFQ-25), Macular Disease Quality of life Questionnaire (MacDQoL) and Low-Luminance Questionnaire (LLD). Participants and setting Twenty-one patients with age-related macular degeneration were recruited from the eye clinic of Southwest Eye Hospital in Chongqing, mainland China. Results The mean age of the participants was 69.8 years (range 57–82 years) and the duration of the disease ranged from 3 months to 6 years. The qualitative analysis revealed nine important domains including symptoms, difficulties with daily activities, depending on others, depression and uncertainty, optimism and hope, social isolation, role change, family support and financial burden. However, all the three questionnaires were insufficient to capture the full extent of quality of life issues of Chinese patients with AMD, and MacDQoL covered more domains when compared with NEI-VFQ-25 and LLD. Conclusion The domains of concepts important to people with AMD in the Chinese culture are not fully represented in the three widely used questionnaires. Nine important domains were identified for the assessment of quality of life and should be considered when assessing the impact of AMD on Chinese individuals. Further studies are needed to develop an AMD quality of life questionnaire, better tailored to the needs and culture of Chinese patients. PMID:29666126

  8. Neutron diffraction study of the formation kinetics of ordered antiphase domains in titanium carbohydride TiCxHy

    International Nuclear Information System (INIS)

    Khidirov, I.

    2015-01-01

    The kinetics of formation and growth of ordered antiphase domains (APDs) in titanium carbohydride TiC 0.50 H 0.21 has been investigated by neutron diffraction. A model of ordered APDs is proposed. It is established that the pronounced ordering of interstitial atoms and APDs begin at 450°C. It is shown that the period of ordered APDs (P ≈ 10–12) is independent of the exposure time at a constant temperature. It is found that the temperature of ordered APDs, T OAPD , increases nonlinearly with an increase in the carbon concentration in the range 0.50 ≤ C/Ti ≤ 0.70. The formation temperature of ordered APDs is found to correlate with the concentration dependence of the order–disorder transition temperature and be 0.60 of the order–disorder transition temperature: T APD = 0.60Τ C

  9. Neutron diffraction study of the formation of ordered antiphase domains in cubic titanium carbide TiC0.60

    International Nuclear Information System (INIS)

    Khidirov, I.; Parpiev, A. S.

    2013-01-01

    A series of superstructural reflections (described within the sp. gr. Fd3m) are found to be split into three symmetric parts in the neutron powder diffraction pattern of titanium carbide TiC 0.60 annealed at a temperature of 600°C. No splitting of superstructural reflections is observed in the neutron diffraction pattern of TiC 0.60 annealed at relatively high temperatures (780°C). This phenomenon can be explained by that fact that the ordering of carbon atoms at relatively high temperatures (780°C) is accompanied by the formation of randomly oriented rather large antiphase domains (APDs) (450 Å). At relatively low temperatures (600°C), stacking faults arise in the arrangement of partially ordered carbon atoms. In this case, relatively small ordered APDs (290 Å) are formed, along with disordered ones.

  10. A case study of the intraseasonal oscillation traversing the TOGA-COARE LSD. [large-scale domain

    Science.gov (United States)

    Vincent, Dayton G.; Schrage, Jon M.; Sliwinski, L. D.

    1993-01-01

    The paper presents examination of tree intraseasonal (30-60 day) oscillations (ISOs) that occurred during the southern summer season (December 1, 1985 - February 28, 1986) traversing the Large-Scale Domain (LSD) TOGA-COARE, the region which also plays an important role in ENSO, Australian monsoon, and extratropical circulations. Data presented include Hovmoeller diagrams of 5-day running means of 250-mb velocity potential anomalies and OLR anomalies; graphs of five-day running means of OLR in precipitable water (W) per sq m, averaged over 10 x 10 deg boxes centered on 5 S and (1) 145 E, (2) 155 E, (3) 165 E, and (4) 165 D, indicating the midpoint of each ISO; and vertical profiles of zonal wind in m/s averaged over the time period that each ISO spends in the 10 x 10 deg box centered at 5 S, and 175 E and 145 E.

  11. Purification, crystallization and preliminary X-ray diffraction study of human ribosomal protein L10 core domain

    International Nuclear Information System (INIS)

    Nishimura, Mitsuhiro; Kaminishi, Tatsuya; Kawazoe, Masahito; Shirouzu, Mikako; Takemoto, Chie; Yokoyama, Shigeyuki; Tanaka, Akiko; Sugano, Sumio; Yoshida, Takuya; Ohkubo, Tadayasu; Kobayashi, Yuji

    2007-01-01

    A truncated variant of human ribosomal protien L10 was prepared and crystallized. Diffraction data were collected to 2.5 Å resolution. Eukaryotic ribosomal protein L10 is an essential component of the large ribosomal subunit, which organizes the architecture of the aminoacyl-tRNA binding site. The human L10 protein is also called the QM protein and consists of 214 amino-acid residues. For crystallization, the L10 core domain (L10CD, Phe34–Glu182) was recombinantly expressed in Escherichia coli and purified to homogeneity. A hexagonal crystal of L10CD was obtained by the sitting-drop vapour-diffusion method. The L10CD crystal diffracted to 2.5 Å resolution and belongs to space group P3 1 21 or P3 2 21

  12. A study of the dynamics of seizure propagation across micro domains in the vicinity of the seizure onset zone.

    Science.gov (United States)

    Basu, Ishita; Kudela, Pawel; Korzeniewska, Anna; Franaszczuk, Piotr J; Anderson, William S

    2015-08-01

    The use of micro-electrode arrays to measure electrical activity from the surface of the brain is increasingly being investigated as a means to improve seizure onset zone (SOZ) localization. In this work, we used a multivariate autoregressive model to determine the evolution of seizure dynamics in the [Formula: see text] Hz high frequency band across micro-domains sampled by such micro-electrode arrays. We showed that a directed transfer function (DTF) can be used to estimate the flow of seizure activity in a set of simulated micro-electrode data with known propagation pattern. We used seven complex partial seizures recorded from four patients undergoing intracranial monitoring for surgical evaluation to reconstruct the seizure propagation pattern over sliding windows using a DTF measure. We showed that a DTF can be used to estimate the flow of seizure activity in a set of simulated micro-electrode data with a known propagation pattern. In general, depending on the location of the micro-electrode grid with respect to the clinical SOZ and the time from seizure onset, ictal propagation changed in directional characteristics over a 2-10 s time scale, with gross directionality limited to spatial dimensions of approximately [Formula: see text]. It was also seen that the strongest seizure patterns in the high frequency band and their sources over such micro-domains are more stable over time and across seizures bordering the clinically determined SOZ than inside. This type of propagation analysis might in future provide an additional tool to epileptologists for characterizing epileptogenic tissue. This will potentially help narrowing down resection zones without compromising essential brain functions as well as provide important information about targeting anti-epileptic stimulation devices.

  13. Spectral-domain optical coherence tomography study on dynamic changes of human tears after instillation of artificial tears.

    Science.gov (United States)

    Napoli, Pietro Emanuele; Satta, Giovanni Maria; Coronella, Franco; Fossarello, Maurizio

    2014-07-01

    To analyze in vivo the dynamic changes induced by different artificial tears (ATs) in the precorneal tear film (PCTF) and lower tear meniscus (LTM) by using spectral-domain (SD) anterior segment optical coherence tomography (OCT). We prospectively examined 42 normal human eyes by using SD-OCT imaging. On the day before OCT imaging, all enrolled subjects were evaluated for abnormalities of ocular surface. All tear film images were obtained before and after instillation of three different types of ATs (mucomimetic, lipid-based, and saline) in five serial scans: immediately (within 30 seconds), at the first, fifth, 10th, and 20th minute. Subjects received a drop of 35 μL in one randomly selected eye. All examinations were conducted in the same conditions of temperature, brightness, humidity, and time of day. Changes in the morphological pattern of both LTM and PCTF were associated with the type of artificial tear instilled on the ocular surface. Similarly, the radius of curvature (rc), the height (h), and the depth (d) showed dynamic variations depending on treatment. Although by the 20th minute, both h and d returned to baseline values in all groups, a significant difference in rc (compared with baseline) was detected for mucomimetic ATs (P = 0.04) and lipid ATs (P = 0.02). Spectral-domain OCT imaging has preliminarily proved to be a noninvasive tool to evaluate, in real time, the different changes induced by ATs instillation. An important stride in understanding the clinical response to various tear substitutes can be achieved by this objective and quantitative approach. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  14. A study of the dynamics of seizure propagation across micro domains in the vicinity of the seizure onset zone

    Science.gov (United States)

    Basu, Ishita; Kudela, Pawel; Korzeniewska, Anna; Franaszczuk, Piotr J.; Anderson, William S.

    2015-08-01

    Objective. The use of micro-electrode arrays to measure electrical activity from the surface of the brain is increasingly being investigated as a means to improve seizure onset zone (SOZ) localization. In this work, we used a multivariate autoregressive model to determine the evolution of seizure dynamics in the 70-110 Hz high frequency band across micro-domains sampled by such micro-electrode arrays. We showed that a directed transfer function (DTF) can be used to estimate the flow of seizure activity in a set of simulated micro-electrode data with known propagation pattern. Approach. We used seven complex partial seizures recorded from four patients undergoing intracranial monitoring for surgical evaluation to reconstruct the seizure propagation pattern over sliding windows using a DTF measure. Main results. We showed that a DTF can be used to estimate the flow of seizure activity in a set of simulated micro-electrode data with a known propagation pattern. In general, depending on the location of the micro-electrode grid with respect to the clinical SOZ and the time from seizure onset, ictal propagation changed in directional characteristics over a 2-10 s time scale, with gross directionality limited to spatial dimensions of approximately 9 m{{m}2}. It was also seen that the strongest seizure patterns in the high frequency band and their sources over such micro-domains are more stable over time and across seizures bordering the clinically determined SOZ than inside. Significance. This type of propagation analysis might in future provide an additional tool to epileptologists for characterizing epileptogenic tissue. This will potentially help narrowing down resection zones without compromising essential brain functions as well as provide important information about targeting anti-epileptic stimulation devices.

  15. Separating Cognitive and Content Domains in Mathematical Competence

    Science.gov (United States)

    Harks, Birgit; Klieme, Eckhard; Hartig, Johannes; Leiss, Dominik

    2014-01-01

    The present study investigates the empirical separability of mathematical (a) content domains, (b) cognitive domains, and (c) content-specific cognitive domains. There were 122 items representing two content domains (linear equations vs. theorem of Pythagoras) combined with two cognitive domains (modeling competence vs. technical competence)…

  16. Domain-general involvement of the posterior frontolateral cortex in time-based resource-sharing in working memory: An fMRI study.

    Science.gov (United States)

    Vergauwe, Evie; Hartstra, Egbert; Barrouillet, Pierre; Brass, Marcel

    2015-07-15

    Working memory is often defined in cognitive psychology as a system devoted to the simultaneous processing and maintenance of information. In line with the time-based resource-sharing model of working memory (TBRS; Barrouillet and Camos, 2015; Barrouillet et al., 2004), there is accumulating evidence that, when memory items have to be maintained while performing a concurrent activity, memory performance depends on the cognitive load of this activity, independently of the domain involved. The present study used fMRI to identify regions in the brain that are sensitive to variations in cognitive load in a domain-general way. More precisely, we aimed at identifying brain areas that activate during maintenance of memory items as a direct function of the cognitive load induced by both verbal and spatial concurrent tasks. Results show that the right IFJ and bilateral SPL/IPS are the only areas showing an increased involvement as cognitive load increases and do so in a domain general manner. When correlating the fMRI signal with the approximated cognitive load as defined by the TBRS model, it was shown that the main focus of the cognitive load-related activation is located in the right IFJ. The present findings indicate that the IFJ makes domain-general contributions to time-based resource-sharing in working memory and allowed us to generate the novel hypothesis by which the IFJ might be the neural basis for the process of rapid switching. We argue that the IFJ might be a crucial part of a central attentional bottleneck in the brain because of its inability to upload more than one task rule at once. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Extrapolation of Inter Domain Communications and Substrate Binding Cavity of Camel HSP70 1A: A Molecular Modeling and Dynamics Simulation Study.

    Directory of Open Access Journals (Sweden)

    Saurabh Gupta

    Full Text Available Heat shock protein 70 (HSP70 is an important chaperone, involved in protein folding, refolding, translocation and complex remodeling reactions under normal as well as stress conditions. However, expression of HSPA1A gene in heat and cold stress conditions associates with other chaperons and perform its function. Experimental structure for Camel HSP70 protein (cHSP70 has not been reported so far. Hence, we constructed 3D models of cHSP70 through multi- template comparative modeling with HSP110 protein of S. cerevisiae (open state and with HSP70 protein of E. coli 70kDa DnaK (close state and relaxed them for 100 nanoseconds (ns using all-atom Molecular Dynamics (MD Simulation. Two stable conformations of cHSP70 with Substrate Binding Domain (SBD in open and close states were obtained. The collective mode analysis of different transitions of open state to close state and vice versa was examined via Principal Component Analysis (PCA and Minimum Distance Matrix (MDM. The results provide mechanistic representation of the communication between Nucleotide Binding Domain (NBD and SBD to identify the role of sub domains in conformational change mechanism, which leads the chaperone cycle of cHSP70. Further, residues present in the chaperon functioning site were also identified through protein-peptide docking. This study provides an overall insight into the inter domain communication mechanism and identification of the chaperon binding cavity, which explains the underlying mechanism involved during heat and cold stress conditions in camel.

  18. Dynamically Coupled Residues within the SH2 Domain of FYN Are Key to Unlocking Its Activity.

    Science.gov (United States)

    Huculeci, Radu; Cilia, Elisa; Lyczek, Agatha; Buts, Lieven; Houben, Klaartje; Seeliger, Markus A; van Nuland, Nico; Lenaerts, Tom

    2016-11-01

    Src kinase activity is controlled by various mechanisms involving a coordinated movement of kinase and regulatory domains. Notwithstanding the extensive knowledge related to the backbone dynamics, little is known about the more subtle side-chain dynamics within the regulatory domains and their role in the activation process. Here, we show through experimental methyl dynamic results and predicted changes in side-chain conformational couplings that the SH2 structure of Fyn contains a dynamic network capable of propagating binding information. We reveal that binding the phosphorylated tail of Fyn perturbs a residue cluster near the linker connecting the SH2 and SH3 domains of Fyn, which is known to be relevant in the regulation of the activity of Fyn. Biochemical perturbation experiments validate that those residues are essential for inhibition of Fyn, leading to a gain of function upon mutation. These findings reveal how side-chain dynamics may facilitate the allosteric regulation of the different members of the Src kinase family. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Evaluating process domains in small arid granitic watersheds: Case study of Pima Wash, South Mountains, Sonoran Desert, USA

    Science.gov (United States)

    Seong, Yeong Bae; Larson, Phillip H.; Dorn, Ronald I.; Yu, Byung Yong

    2016-02-01

    This paper provides support for the concept of geomorphic process domains developed by Montgomery (1999) by linking geomorphic processes to ecological variations seen in the Pima arid granitic watershed of the Sonoran Desert, Phoenix, Arizona. Closer joint spacing shows a statistically significant correlation with lower percentages of mineral grain attachment as measured by digital image processing of backscattered electron microscope imagery. Lower mineral grain attachment leads to more frequent spalling of rock surfaces, as measured by varnish microlamination (VML) ages of the last spalling event. In contrast, more distant joint spacing leads to in situ 10Be erosion rates of 3.4-8.5 mm/ka and the emergence of low domes and kopje granitic landforms; these low domes also serve as knickpoints along ephemeral washes. Distant jointing thus plays a key role in generating the bare bedrock surfaces that funnel limited precipitation to bedrock margins - enhancing the canopy cover of perennial plants next to the bare bedrock. Joint-influenced geomorphic processes at Pima Wash generate four distinct process domains: (PD1) armored drainage divides; (PD2) slopes with different granite landforms; (PD3) mid- and upper basin channels that mix knickzones, strath floodplains, and sandy alluvial sections; and (PD4) the main ephemeral channel transitioning to the piedmont. Distant jointing promotes bedrock exposure and rock armoring along drainage divides in PD1 that then concentrates runoff and promotes perennial plant growth. More distant joint spacing on slopes in PD2 promotes exposure of granitic bedrock forms that shed overland flow to their margin and promotes flora and fauna growths along the margins of low granitic domes and kopjes. Similarly, wider joint spacing along ephemeral washes in PD3 leads to knickpoints, which in turn act to concentrate moisture immediately downstream. The stream terraces in PD4 influence the ecology through xeric desert pavements on terrace treads

  20. Anisotropy of domain wall resistance

    Science.gov (United States)

    Viret; Samson; Warin; Marty; Ott; Sondergard; Klein; Fermon

    2000-10-30

    The resistive effect of domain walls in FePd films with perpendicular anisotropy was studied experimentally as a function of field and temperature. The films were grown directly on MgO substrates, which induces an unusual virgin magnetic configuration composed of 60 nm wide parallel stripe domains. This allowed us to carry out the first measurements of the anisotropy of domain wall resistivity in the two configurations of current perpendicular and parallel to the walls. At 18 K, we find 8.2% and 1.3% for the domain wall magnetoresistance normalized to the wall width (8 nm) in these two respective configurations. These values are consistent with the predictions of Levy and Zhang.

  1. A first-principles study of lithium-decorated hybrid boron nitride and graphene domains for hydrogen storage

    International Nuclear Information System (INIS)

    Hu, Zi-Yu; Shao, Xiaohong; Wang, Da; Liu, Li-Min; Johnson, J. Karl

    2014-01-01

    First-principles calculations are performed to investigate the adsorption of hydrogen onto Li-decorated hybrid boron nitride and graphene domains of (BN) x C 1−x complexes with x = 1, 0.25, 0.5, 0.75, 0, and B 0.125 C 0.875 . The most stable adsorption sites for the nth hydrogen molecule in the lithium-decorated (BN) x C 1−x complexes are systematically discussed. The most stable adsorption sites were affected by the charge localization, and the hydrogen molecules were favorably located above the C-C bonds beside the Li atom. The results show that the nitrogen atoms in the substrate planes could increase the hybridization between the 2p orbitals of Li and the orbitals of H 2 . The results revealed that the (BN) x C 1−x complexes not only have good thermal stability but they also exhibit a high hydrogen storage of 8.7% because of their dehydrogenation ability

  2. Counteracting Domain Loss and Epistemicide in Specialized Discourse: A Case Study on the Translation of Anglophone Metaphors to French

    Directory of Open Access Journals (Sweden)

    Geneviève Bordet

    2016-06-01

    Full Text Available The dominance of English as the world language of publication has had a decisive impact on the dissemination of information and innovation across cultures, with a resulting tendency to a standardization of scientific conceptualization. This dominance does not only impact scientific and academic discourse, but also the whole range of professional and technical texts representative of various specialized discourses. This paper advocates engaging in the practice of dynamic translation to keep non-English specialized languages alive. Advanced students’ analysis of translation projects yields revealing examples of conflicting views of the world, between English and French, in emerging and controversial fields such as “shadow banking” or “human branding”. The students’ evaluation of alternative solutions to problems of equivalence highlights the cultural gaps which exist within global fields of knowledge and can be interpreted in terms of the intercultural and interlinguistic transfer of specialized metaphor. It is shown that the practice and analysis of translation provide an appropriate approach for a better understanding of languages for specific purposes (LSP and the development of awareness of domain loss and epistemicide.

  3. Optical study of the skeletal muscle during exercise with a second-generation frequency-domain tissue oximeter

    Science.gov (United States)

    Franceschini, Maria-Angela; Wallace, Don J.; Barbieri, Beniamino B.; Fantini, Sergio; Mantulin, William W.; Pratesi, Simone; Donzelli, Gian Paolo; Gratton, Enrico

    1997-08-01

    We present a re-engineered frequency-domain tissue oximeter operating in the near-infrared spectral region. This instrument is based on the multi-distance measurement protocol, which we have implemented in our original design by multiplexing multiple light sources. The new instrument uses intensity modulated (110 MHz) laser diodes emitting at 750 and 840 nm. The laser diodes are coupled to glass optical fibers (600 micrometer core diameter). The average light intensity delivered to the tissue is about 3 mW. The multiplexing electronics are based on solid state switches that allow for acquisition times per point as short as tens of milliseconds. Our tests on phantoms and in vivo with the new oximeter have shown significant improvement in terms of stability, reliability, and reproducibility with respect to the original prototype. Furthermore, by using optical fibers we achieve a high versatility in the design of the measuring probe, permitting custom design for various tissue contours and different measurements. To verify the improved performance of the new oximeter, we have performed an in vivo test consisting of monitoring the hemoglobin saturation (Y) and concentration (THC) on the calf of 18 healthy volunteers during walking and running routines.

  4. Self-concept in adolescence: a longitudinal study on reciprocal effects of self-perceptions in academic and social domains.

    Science.gov (United States)

    Preckel, Franzis; Niepel, Christoph; Schneider, Marian; Brunner, Martin

    2013-12-01

    Fostering social and academic self-concepts are central educational goals. During mid-adolescence academic engagement and success seem to be devalued by peers and to be negatively associated with students' social standing. For this age group, is the development of a positive academic self-concept compatible with the development of a positive social self-concept? We investigated relations among academic self-concept, social self-concept, and academic achievement. 1282 students (47.60% female) participated in three-waves of measurement in Grade 5, 6, and 8. Earlier social self-concept of acceptance negatively predicted changes in academic self-concept over time while earlier social self-concept of assertion positively predicted changes in academic self-concept. There were no significant relations between social self-concepts and achievement but positive reciprocal relations between academic self-concept and achievement. Results indicate that fostering adolescents self-concept in social and academic domains are compatible goals. However, some students need support in managing the challenge to coordinate social and academic goals. Copyright © 2013 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

  5. A Steric-inhibition model for regulation of nucleotide exchange via the Dock180 family of GEFs.

    Science.gov (United States)

    Lu, Mingjian; Kinchen, Jason M; Rossman, Kent L; Grimsley, Cynthia; Hall, Matthew; Sondek, John; Hengartner, Michael O; Yajnik, Vijay; Ravichandran, Kodi S

    2005-02-22

    CDM (CED-5, Dock180, Myoblast city) family members have been recently identified as novel, evolutionarily conserved guanine nucleotide exchange factors (GEFs) for Rho-family GTPases . They regulate multiple processes, including embryonic development, cell migration, apoptotic-cell engulfment, tumor invasion, and HIV-1 infection, in diverse model systems . However, the mechanism(s) of regulation of CDM proteins has not been well understood. Here, our studies on the prototype member Dock180 reveal a steric-inhibition model for regulating the Dock180 family of GEFs. At basal state, the N-terminal SH3 domain of Dock180 binds to the distant catalytic Docker domain and negatively regulates the function of Dock180. Further studies revealed that the SH3:Docker interaction sterically blocks Rac access to the Docker domain. Interestingly, ELMO binding to the SH3 domain of Dock180 disrupted the SH3:Docker interaction, facilitated Rac access to the Docker domain, and contributed to the GEF activity of the Dock180/ELMO complex. Additional genetic rescue studies in C. elegans suggested that the regulation of the Docker-domain-mediated GEF activity by the SH3 domain and its adjoining region is evolutionarily conserved. This steric-inhibition model may be a general mechanism for regulating multiple SH3-domain-containing Dock180 family members and may have implications for a variety of biological processes.

  6. Associations among workplace environment, self-regulation, and domain-specific physical activities among white-collar workers: a multilevel longitudinal study.

    Science.gov (United States)

    Watanabe, Kazuhiro; Kawakami, Norito; Otsuka, Yasumasa; Inoue, Shigeru

    2018-05-31

    Psychological and environmental determinants have been discussed for promoting physical activity among workers. However, few studies have investigated effects of both workplace environment and psychological determinants on physical activity. It is also unknown which domains of physical activities are promoted by these determinants. This study aimed to investigate main and interaction effects of workplace environment and individual self-regulation for physical activity on domain-specific physical activities among white-collar workers. A multi-site longitudinal study was conducted at baseline and about 5-month follow-up. A total of 49 worksites and employees within the worksites were recruited. Inclusion criteria for the worksites (a) were located in the Kanto area, Japan and (b) employed two or more employees. Employee inclusion criteria were (a) employed by the worksites, (b) aged 18 years or older, and (c) white-collar workers. For outcomes, three domain-specific physical activities (occupational, transport-related, and leisure-time) at baseline and follow-up were measured. For independent variables, self-regulation for physical activity, workplace environments (parking/bike, signs/bulletin boards/advertisements, stairs/elevators, physical activity/fitness facilities, work rules, written policies, and health promotion programs), and covariates at baseline were measured. Hierarchical Linear Modeling was conducted to investigate multilevel associations. Of the recruited worksites, 23 worksites and 562 employees, and 22 worksites and 459 employees completed the baseline and the follow-up surveys. As results of Hierarchical Linear Modeling, stairs/elevator (γ=3.80 [SE=1.80], ppsychological approaches to increase effect sizes to promote overall physical activity.

  7. Study of turbulence of Lower Hybrid Drift Instability origin with the Multi Level Multi Domain semi-implicit adaptive PIC method

    Science.gov (United States)

    Innocenti, Maria Elena; Beck, Arnaud; Markidis, Stefano; Lapenta, Giovanni

    2015-04-01

    We study turbulence generated by the Lower Hybrid Drift Instability (LHDI [1]) in the terrestrial magnetosphere. The problem is not only of interest per se, but also for the implications it can have for the so-called turbulent reconnection. The LHDI evolution is simulated with the PIC Multi Level Multi Domain code Parsek2D-MLMD [2,3], which simulates different parts of the domain with different spatial and temporal resolutions. This allows to satisfy, at a low computing cost, the two necessary requirements for LHDI turbulence simulations: 1) a large domain, to capture the high wavelength branch of the LHDI and of the secondary kink instability and 2) high resolution, to cover the high wavenumber part of the power spectrum and to capture the wavenumber at which the turbulent cascade ends. The turbulent cascade proceeds seamlessly from the coarse (low resolution) to the refined (high resolution) grid, the only one resolved enough to capture its end, which is studied here and related to wave-particle interaction processes. We also comment upon the role of smoothing (a common technique used in PIC simulations to reduce particle noise, [4]) in simulations of turbulence and on how its effects on power spectra may be easily mistaken, in absence of accurate convergence studies, for the end of the inertial range. [1] P. Gary, Theory of space plasma microinstabilities, Cambridge Atmospheric and Space Science Series, 2005. [2] M. E. Innocenti, G. Lapenta, S. Markidis, A. Beck, A. Vapirev, Journal of Computational Physics 238 (2013) 115 - 140. [3] M. E. Innocenti, A. Beck, T. Ponweiser, S. Markidis, G. Lapenta, Computer Physics Communications (accepted) (2014). [4] C. K. Birdsall, A. B. Langdon, Plasma physics via computer simulation, Taylor and Francis, 2004.

  8. L'apprentissage des langues médiatisé par les technologies (ALMT – Étude d'un domaine de recherche émergent à travers les publications de la revue Alsic Technology-mediated language learning: an emergent research domain under study through the review of a French scientific journal's publications

    Directory of Open Access Journals (Sweden)

    Nicolas Guichon

    2012-11-01

    Full Text Available Dans cette étude, il est postulé que l'apprentissage des langues médiatisé par les technologies (ALMT est un domaine de recherche qui s'intéresse au développement et à l'intégration des technologies dans l'enseignement-apprentissage d'une langue. Ce domaine étant émergent, la présente recherche vise tout d'abord à comprendre comment s'est formée la communauté de chercheurs autour de cet objet. Puis, à travers l'analyse critique de 79 articles publiés dans la revue en ligne francophone Alsic entre 1998 et 2010, la présente contribution s'emploie à définir les contours épistémologiques de ce domaine en étudiant les moyens de production de connaissance.In this study, it is postulated that technology mediated language learning is a research domain that focuses on the design and integration of technologies for language learning and teaching. Because this domain is emergent, the present study first aims at understanding how a community of researchers has developed around this object. Then, thanks to the critical analysis of 79 articles published in Alsic, a French-speaking online journal, the present article endeavours to define the epistemological contours of this research domain by studying the means employed to produce knowledge.

  9. EH domain of EHD1

    Energy Technology Data Exchange (ETDEWEB)

    Kieken, Fabien; Jovic, Marko; Naslavsky, Naava; Caplan, Steve, E-mail: scaplan@unmc.edu; Sorgen, Paul L. [University of Nebraska Medical Center, Department of Biochemistry and Molecular Biology and Eppley Cancer Center (United States)], E-mail: psorgen@unmc.edu

    2007-12-15

    EHD1 is a member of the mammalian C-terminal Eps15 homology domain (EH) containing protein family, and regulates the recycling of various receptors from the endocytic recycling compartment to the plasma membrane. The EH domain of EHD1 binds to proteins containing either an Asn-Pro-Phe or Asp-Pro-Phe motif, and plays an important role in the subcellular localization and function of EHD1. Thus far, the structures of five N-terminal EH domains from other proteins have been solved, but to date, the structure of the EH domains from the four C-terminal EHD family paralogs remains unknown. In this study, we have assigned the 133 C-terminal residues of EHD1, which includes the EH domain, and solved its solution structure. While the overall structure resembles that of the second of the three N-terminal Eps15 EH domains, potentially significant differences in surface charge and the structure of the tripeptide-binding pocket are discussed.

  10. EH domain of EHD1

    International Nuclear Information System (INIS)

    Kieken, Fabien; Jovic, Marko; Naslavsky, Naava; Caplan, Steve; Sorgen, Paul L.

    2007-01-01

    EHD1 is a member of the mammalian C-terminal Eps15 homology domain (EH) containing protein family, and regulates the recycling of various receptors from the endocytic recycling compartment to the plasma membrane. The EH domain of EHD1 binds to proteins containing either an Asn-Pro-Phe or Asp-Pro-Phe motif, and plays an important role in the subcellular localization and function of EHD1. Thus far, the structures of five N-terminal EH domains from other proteins have been solved, but to date, the structure of the EH domains from the four C-terminal EHD family paralogs remains unknown. In this study, we have assigned the 133 C-terminal residues of EHD1, which includes the EH domain, and solved its solution structure. While the overall structure resembles that of the second of the three N-terminal Eps15 EH domains, potentially significant differences in surface charge and the structure of the tripeptide-binding pocket are discussed

  11. Structures of class A macrophage scavenger receptors. Electron microscopic study of flexible, multidomain, fibrous proteins and determination of the disulfide bond pattern of the scavenger receptor cysteine-rich domain.

    Science.gov (United States)

    Resnick, D; Chatterton, J E; Schwartz, K; Slayter, H; Krieger, M

    1996-10-25

    Structures of secreted forms of the human type I and II class A macrophage scavenger receptors were studied using biochemical and biophysical methods. Proteolytic analysis was used to determine the intramolecular disulfide bonds in the type I-specific scavenger receptor cysteine-rich (SRCR) domain: Cys2-Cys7, Cys3-Cys8, and Cys5-Cys6. This pattern is likely to be shared by the highly homologous domains in the many other members of the SRCR domain superfamily. Electron microscopy using rotary shadowing and negative staining showed that the type I and II receptors are extended molecules whose contour lengths are approximately 440 A. They comprised two adjacent fibrous segments, an alpha-helical coiled-coil ( approximately 230 A, including a contribution from the N-terminal spacer domain) and a collagenous triple helix ( approximately 210 A). The type I molecules also contained a C-terminal globular structure ( approximately 58 x 76 A) composed of three SRCR domains. The fibrous domains were joined by an extremely flexible hinge. The angle between these domains varied from 0 to 180 degrees and depended on the conditions of sample preparation. Unexpectedly, at physiologic pH, the prevalent angle seen using rotary shadowing was 0 degrees , resulting in a structure that is significantly more compact than previously suggested. The apparent juxtaposition of the fibrous domains at neutral pH provides a framework for future structure-function studies of these unusual multiligand receptors.

  12. A Logic for Inclusion of Administrative Domains and Administrators in Multi-domain Authorization

    Science.gov (United States)

    Iranmanesh, Zeinab; Amini, Morteza; Jalili, Rasool

    Authorization policies for an administrative domain or a composition of multiple domains in multi-domain environments are determined by either one administrator or multiple administrators' cooperation. Several logic-based models for multi-domain environments' authorization have been proposed; however, they have not considered administrators and administrative domains in policies' representation. In this paper, we propose the syntax, proof theory, and semantics of a logic for multi-domain authorization policies including administrators and administrative domains. Considering administrators in policies provides the possibility of presenting composite administration having applicability in many collaborative applications. Indeed, administrators and administrative domains stated in policies can be used in authorization. The presented logic is based on modal logic and utilizes two calculi named the calculus of administrative domains and the calculus of administrators. It is also proved that the logic is sound. A case study is presented signifying the logic application in practical projects.

  13. Word Domain Disambiguation via Word Sense Disambiguation

    Energy Technology Data Exchange (ETDEWEB)

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

    2006-06-04

    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.

  14. On the structure of order domains

    DEFF Research Database (Denmark)

    Geil, Olav; Pellikaan, Ruud

    2002-01-01

    The notion of an order domain is generalized. The behaviour of an order domain by taking a subalgebra, the extension of scalars, and the tensor product is studied. The relation of an order domain with valuation theory, Gröbner algebras, and graded structures is given. The theory of Gröbner bases...... for order domains is developed and used to show that the factor ring theorem and its converse, the presentation theorem, hold. The dimension of an order domain is related to the rank of its value semigroup....

  15. Ferroelectric domain continuity over grain boundaries

    DEFF Research Database (Denmark)

    Mantri, Sukriti; Oddershede, Jette; Damjanovic, Dragan

    2017-01-01

    Formation and mobility of domain walls in ferroelectric materials is responsible for many of their electrical and mechanical properties. Domain wall continuity across grain boundaries has been observed since the 1950's and is speculated to affect the grain boundary-domain interactions, thereby...... impacting macroscopic ferroelectric properties in polycrystalline systems. However detailed studies of such correlated domain structures across grain boundaries are limited. In this work, we have developed the mathematical requirements for domain wall plane matching at grain boundaries of any given...... orientation. We have also incorporated the effect of grain boundary ferroelectric polarization charge created when any two domains meet at the grain boundary plane. The probability of domain wall continuity for three specific grain misorientations is studied. Use of this knowledge to optimize processing...

  16. Higher risk of death among MEN1 patients with mutations in the JunD interacting domain: a Groupe d'etude des Tumeurs Endocrines (GTE) cohort study.

    Science.gov (United States)

    Thevenon, Julien; Bourredjem, Abderrahmane; Faivre, Laurence; Cardot-Bauters, Catherine; Calender, Alain; Murat, Arnaud; Giraud, Sophie; Niccoli, Patricia; Odou, Marie-Françoise; Borson-Chazot, Françoise; Barlier, Anne; Lombard-Bohas, Catherine; Clauser, Eric; Tabarin, Antoine; Parfait, Béatrice; Chabre, Olivier; Castermans, Emilie; Beckers, Albert; Ruszniewski, Philippe; Le Bras, Morgane; Delemer, Brigitte; Bouchard, Philippe; Guilhem, Isabelle; Rohmer, Vincent; Goichot, Bernard; Caron, Philippe; Baudin, Eric; Chanson, Philippe; Groussin, Lionel; Du Boullay, Hélène; Weryha, Georges; Lecomte, Pierre; Penfornis, Alfred; Bihan, Hélène; Archambeaud, Françoise; Kerlan, Véronique; Duron, Françoise; Kuhn, Jean-Marc; Vergès, Bruno; Rodier, Michel; Renard, Michel; Sadoul, Jean-Louis; Binquet, Christine; Goudet, Pierre

    2013-05-15

    Multiple endocrine neoplasia syndrome type 1 (MEN1), which is secondary to mutation of the MEN1 gene, is a rare autosomal-dominant disease that predisposes mutation carriers to endocrine tumors. Although genotype-phenotype studies have so far failed to identify any statistical correlations, some families harbor recurrent tumor patterns. The function of MENIN is unclear, but has been described through the discovery of its interacting partners. Mutations in the interacting domains of MENIN functional partners have been shown to directly alter its regulation abilities. We report on a cohort of MEN1 patients from the Groupe d'étude des Tumeurs Endocrines. Patients with a molecular diagnosis and a clinical follow-up, totaling 262 families and 806 patients, were included. Associations between mutation type, location or interacting factors of the MENIN protein and death as well as the occurrence of MEN1-related tumors were tested using a frailty Cox model to adjust for potential heterogeneity across families. Accounting for the heterogeneity across families, the overall risk of death was significantly higher when mutations affected the JunD interacting domain (adjusted HR = 1.88: 95%-CI = 1.15-3.07). Patients had a higher risk of death from cancers of the MEN1 spectrum (HR = 2.34; 95%-CI = 1.23-4.43). This genotype-phenotype correlation study confirmed the lack of direct genotype-phenotype correlations. However, patients with mutations affecting the JunD interacting domain had a higher risk of death secondary to a MEN1 tumor and should thus be considered for surgical indications, genetic counseling and follow-up.

  17. The effect of education on age-related changes in three cognitive domains: a cross-sectional study in primary care.

    Science.gov (United States)

    Martins, Isabel Pavão; Maruta, Carolina; Silva, Cláudia; Rodrigues, Pedro; Chester, Catarina; Ginó, Sandra; Freitas, Vanda; Freitas, Sara; Oliveira, António Gouveia

    2012-01-01

    The present study aims to investigate the protective effect of formal education on age-related changes in different cognitive domains with the hypothesis that it may attenuate the rate of decline. Individuals aged 50 years or older attending primary care physicians without known brain disease (431 participants, mostly [60.3%] female with 66.3 [±9.1] years of age and 7.7 [±4.1] years of education, on average), were evaluated with a neuropsychological battery including 28 cognitive measures. Cognitive domains identified by factor analysis were subject to repeated multiple regression analyses to determine the variance explained by age and education controlling for gender, depressive symptoms, and vascular risk factors. The slope of the regression equation was compared between two educational groups with an average of 4 years and 11 years of education, respectively. Factors identified corresponded to processing ability (Factor 1), memory (Factor 2), and acquired knowledge (Factor 3). Although education improved performance in Factors 1 and 3, it did not change the slope of age-related decline in any factor. This study suggests that in culturally heterogeneous groups, small increments in education enhance cognition but do not modify the rate of decline of executive functioning with age. These results contradict some clinical findings and need to be confirmed in longitudinal studies.

  18. Relationship between total and segmental bone mineral density and different domains of physical activity among children and adolescents: cross-sectional study.

    Science.gov (United States)

    Diniz, Tiego Aparecido; Agostinete, Ricardo Ribeiro; Costa, Paulo; Saraiva, Bruna Thamyres Ciccotti; Sonvenso, Diego Kanashiro; Freitas, Ismael Forte; Fernandes, Rômulo Araujo; Christofaro, Diego Giulliano Destro

    2017-01-01

    This study aimed to investigate the relationship between total and segmental bone mineral density (BDM) and physical activity (PA) in different domains (school, leisure and sports) among adolescents and children. Cross-sectional study in the Universidade Estadual Paulista Júlio de Mesquita Filho (UNESP). The study sample consisted of 173 children and adolescents (10.31 ± 1.87 years). The BMDs for the whole body (WB) and the regions of the trunk and legs were measured using dual energy X-ray absorptiometry (DXA). PA was measured using the Baecke questionnaire. A regression model was used to analyze the relationship between all the BMDs and the different domains of PA. 41.5% of the adolescents had high percentages of body fat. Regarding the comparison between physically active and insufficiently active adolescents, there were no statistically significant differences in any BMD variables (P > 0.05). The BMD of the legs showed positive relationships with the total PA (β = 0.009; P = 0.013) and sports PA (β = 0.010; P = 0.049) after insertion of the confounders. Similarly, the WB BMD showed the same relationships (total PA: β = 0.005; P = 0.045; and sports PA: β = 0.008; P = 0.049). No relationship was found between leisure and school PA and any of the BMDs (P > 0.05). The results indicated that practice of sport was related to higher BMD values, independent of sex, age and body fatness.

  19. Neuroimaging studies of practice-related change: fMRI and meta-analytic evidence of a domain-general control network for learning.

    Science.gov (United States)

    Chein, Jason M; Schneider, Walter

    2005-12-01

    Functional magnetic resonance imaging and a meta-analysis of prior neuroimaging studies were used to characterize cortical changes resulting from extensive practice and to evaluate a dual-processing account of the neural mechanisms underlying human learning. Three core predictions of the dual processing theory are evaluated: 1) that practice elicits generalized reductions in regional activity by reducing the load on the cognitive control mechanisms that scaffold early learning; 2) that these control mechanisms are domain-general; and 3) that no separate processing pathway emerges as skill develops. To evaluate these predictions, a meta-analysis of prior neuroimaging studies and a within-subjects fMRI experiment contrasting unpracticed to practiced performance in a paired-associate task were conducted. The principal effect of practice was found to be a reduction in the extent and magnitude of activity in a cortical network spanning bilateral dorsal prefrontal, left ventral prefrontal, medial frontal (anterior cingulate), left insular, bilateral parietal, and occipito-temporal (fusiform) areas. These activity reductions are shown to occur in common regions across prior neuroimaging studies and for both verbal and nonverbal paired-associate learning in the present fMRI experiment. The implicated network of brain regions is interpreted as a domain-general system engaged specifically to support novice, but not practiced, performance.

  20. Domain-to-domain coupling in voltage-sensing phosphatase.

    Science.gov (United States)

    Sakata, Souhei; Matsuda, Makoto; Kawanabe, Akira; Okamura, Yasushi

    2017-01-01

    Voltage-sensing phosphatase (VSP) consists of a transmembrane voltage sensor and a cytoplasmic enzyme region. The enzyme region contains the phosphatase and C2 domains, is structurally similar to the tumor suppressor phosphatase PTEN, and catalyzes the dephosphorylation of phosphoinositides. The transmembrane voltage sensor is connected to the phosphatase through a short linker region, and phosphatase activity is induced upon membrane depolarization. Although the detailed molecular characteristics of the voltage sensor domain and the enzyme region have been revealed, little is known how these two regions are coupled. In addition, it is important to know whether mechanism for coupling between the voltage sensor domain and downstream effector function is shared among other voltage sensor domain-containing proteins. Recent studies in which specific amino acid sites were genetically labeled using a fluorescent unnatural amino acid have enabled detection of the local structural changes in the cytoplasmic region of Ciona intestinalis VSP that occur with a change in membrane potential. The results of those studies provide novel insight into how the enzyme activity of the cytoplasmic region of VSP is regulated by the voltage sensor domain.

  1. Barriers and facilitators for implementing a new screening tool in an emergency department: A qualitative study applying the Theoretical Domains Framework.

    Science.gov (United States)

    Kirk, Jeanette W; Sivertsen, Ditte M; Petersen, Janne; Nilsen, Per; Petersen, Helle V

    2016-10-01

    The aim was to identify the factors that were perceived as most important as facilitators or barriers to the introduction and intended use of a new tool in the emergency department among nurses and a geriatric team. A high incidence of functional decline after hospitalisation for acute medical illness has been shown in the oldest patients and those who are physically frail. In Denmark, more than 35% of older medical patients acutely admitted to the emergency department are readmitted within 90 days after discharge. A new screening tool for use in the emergency department aiming to identify patients at particularly high risk of functional decline and readmission was developed. Qualitative study based on semistructured interviews with nurses and a geriatric team in the emergency department and semistructured single interviews with their managers. The Theoretical Domains Framework guided data collection and analysis. Content analysis was performed whereby new themes and themes already existing within each domain were described. Six predominant domains were identified: (1) professional role and identity; (2) beliefs about consequences; (3) goals; (4) knowledge; (5) optimism and (6) environmental context and resources. The content analysis identified three themes, each containing two subthemes. The themes were professional role and identity, beliefs about consequences and preconditions for a successful implementation. Two different cultures were identified in the emergency department. These cultures applied to different professional roles and identity, different actions and sense making and identified how barriers and facilitators linked to the new screening tool were perceived. The results show that different cultures exist in the same local context and influence the perception of barriers and facilitators differently. These cultures must be identified and addressed when implementation is planned. © 2016 The Authors. Journal of Clinical Nursing Published by John

  2. Teaching as acting : a reconstructive study of an action theoretical approach to research and development in the domain of teaching = Onderwijzen als handelen : een reconstructieve studie van een handelingstheoretische benadering van onderzoek en ontwikkeling in het domein van het onderwijzen

    NARCIS (Netherlands)

    Beijaard, D.

    1990-01-01

    The introduction of this study describes five developments regarding research and development in the domain of teaching. These developments are closely connected with the desire to bridge the gap between the theory and the practice of teaching. Successively, attention is paid to: (1)

  3. Activation of PI3K/Akt signaling by n-terminal SH2 domain mutants of the p85α regulatory subunit of PI3K is enhanced by deletion of its c-terminal SH2 domain.

    Science.gov (United States)

    Hofmann, Bianca T; Jücker, Manfred

    2012-10-01

    The phosphoinositide 3-kinase (PI3K) is frequently activated in human cancer cells due to gain of function mutations in the catalytic (p110) and the regulatory (p85) subunits. The regulatory subunit consists of an SH3 domain and two SH2 domains. An oncogenic form of p85α named p65 lacking the c-terminal SH2 domain (cSH2) has been cloned from an irradiation-induced murine thymic lymphoma and transgenic mice expressing p65 in T lymphocytes develop a lymphoproliferative disorder. We have recently detected a c-terminal truncated form of p85α named p76α in a human lymphoma cell line lacking most of the cSH2 domain due to a frame shift mutation. Here, we report that the deletion of the cSH2 domain enhances the activating effects of the n-terminal SH2 domain (nSH2) mutants K379E and R340E on the PI3K/Akt pathway and micro tumor formation in a focus assay. Further analysis revealed that this transforming effect is mediated by activation of the catalytic PI3K isoform p110α and downstream signaling through mTOR. Our data further support a mechanistic model in which mutations of the cSH2 domain of p85α can abrogate its negative regulatory function on PI3K activity via the nSH2 domain of p85α. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Domain-specific cognitive effects of tramiprosate in patients with mild to moderate Alzheimer's disease: ADAS-cog subscale results from the Alphase Study.

    Science.gov (United States)

    Saumier, D; Duong, A; Haine, D; Garceau, D; Sampalis, J

    2009-11-01

    Tramiprosate (homotaurine, ALZHEMEDTM) was recently investigated for its efficacy, safety and disease-modification effects in a Phase III clinical study in mild to moderate Alzheimer's disease (AD) patients (the Alphase study). The primary cognitive endpoint measure of that study was the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog). To characterize potential cognitive benefits of tramiprosate, the present study describes exploratory analyses performed on scores obtained from the specific ADAS-cog subscales in order to determine whether specific domains of cognition may be differentially affected by tramiprosate, which would not have been evident from the measure's total score. Multi-center, double-blind, randomized, placebo-controlled study. 67 investigative sites in the United States and Canada. A total of 1,052 patients were randomized. Patients were randomized to receive twice a day Placebo (n=353), tramiprosate 100 mg (n=352) and tramiprosate 150 mg (n=347). ADAS-cog assessments were conducted every three months over the 78-week study period. Exploratory analyses were performed by comparing ADAS-cog subscale scores between Placebo and each active treatment arm at each visit. The findings of this analysis revealed statistically significant differences or statistical trends in favour of tramiprosate on six ADAS-cog subscales, namely Following Commands, Language Comprehension, Ideational Praxis, Object Naming, Remembering Test Instructions, and Spoken Language Ability. Differences in favor of Placebo were only observed on the Constructional Praxis subscale. This exploratory analysis suggests that tramiprosate may have some benefit on memory, language and praxis skills in mild to moderate AD individuals. Future clinical studies of tramiprosate should include specialized neuropsychological tests to validate its effects within these cognitive domains.

  5. "Being an English Major, Being a Humanities Student": Connecting Academic Subject Identity in Literary Studies to Other Social Domains

    Science.gov (United States)

    Chan, Evelyn T. Y.

    2016-01-01

    This study examined students' construction of academic subject identity in a university humanities discipline, English literary studies. In so doing, the study aimed to provide an empirically grounded intervention in current debates on the value of the humanities in higher education. Eight students participated in interviews lasting 15-20 minutes…

  6. Identifying factors likely to influence compliance with diagnostic imaging guideline recommendations for spine disorders among chiropractors in North America: a focus group study using the Theoretical Domains Framework

    Directory of Open Access Journals (Sweden)

    Bussières André E

    2012-08-01

    Full Text Available Abstract Background The Theoretical Domains Framework (TDF was developed to investigate determinants of specific clinical behaviors and inform the design of interventions to change professional behavior. This framework was used to explore the beliefs of chiropractors in an American Provider Network and two Canadian provinces about their adherence to evidence-based recommendations for spine radiography for uncomplicated back pain. The primary objective of the study was to identify chiropractors’ beliefs about managing uncomplicated back pain without x-rays and to explore barriers and facilitators to implementing evidence-based recommendations on lumbar spine x-rays. A secondary objective was to compare chiropractors in the United States and Canada on their beliefs regarding the use of spine x-rays. Methods Six focus groups exploring beliefs about managing back pain without x-rays were conducted with a purposive sample. The interview guide was based upon the TDF. Focus groups were digitally recorded, transcribed verbatim, and analyzed by two independent assessors using thematic content analysis based on the TDF. Results Five domains were identified as likely relevant. Key beliefs within these domains included the following: conflicting comments about the potential consequences of not ordering x-rays (risk of missing a pathology, avoiding adverse treatment effects, risks of litigation, determining the treatment plan, and using x-ray-driven techniques contrasted with perceived benefits of minimizing patient radiation exposure and reducing costs; beliefs about consequences; beliefs regarding professional autonomy, professional credibility, lack of standardization, and agreement with guidelines widely varied ( social/professional role & identity; the influence of formal training, colleagues, and patients also appeared to be important factors ( social influences; conflicting comments regarding levels of confidence and comfort in managing patients

  7. Study of the influence of micro-structures and porosity of pellets alumina in the ultrasonic pulse in the frequency domain

    International Nuclear Information System (INIS)

    Costa, Antonio Mario Leal Martins

    2009-01-01

    This work is part of a study to the applicability of ultrasonic technique in the frequency domain for non-destructive characterization of ceramic pellets fuel, which is of great interest because of concern about the safety and efficacy in the nuclear industry. In this work it was analysed if there were changes in frequency spectrum, generated by the traveling of an ultrasonic pulse through ceramic pellets of aluminum oxide (Al 2 O 3 ). Using the ultrasonic technique in the frequency domain, together with micro-structural analysis of pellets by scanning electron microscope, it was possible to associate the characteristics of the material inspected with its respective frequency spectrum. The characterization was performed on 40 pellets alumina sintered in the temperatures of 1150, 1400, 1480, 1540 and 1580 deg C with porosities, as measured by the Archimedes method, ranging from 5.09% to 37.3%. The results show that the ultrasonic technique is effective in determining the micro-structure of ceramic alumina pellets and can be applied in the characterization of other porous materials in a production line, where the format of the frequency spectrum generated by the structure of the material may determine if the pellets belong the required specifications. (author)

  8. Small-angle scattering studies show distinct conformations of calmodulin in its complexes with two peptides based on the regulatory domain of the catalytic subunit of phosphorylase kinase

    International Nuclear Information System (INIS)

    Trewhella, J.; Blumenthal, D.K.; Rokop, S.E.; Seeger, P.A.

    1990-01-01

    Small-angle X-ray and neutron scattering have been used to study the solution structures of calmodulin complexed with synthetic peptides corresponding to residues 342-366 and 301-326, designated PhK5 and PhK13, respectively, in the regulatory domain of the catalytic subunit of skeletal muscle phosphorylase kinase. The scattering data show that binding of PhK5 to calmodulin induces a dramatic contraction of calmodulin, similar to that previously observed when calmodulin is complexed with the calmodulin-binding domain peptide from rabbit skeletal muscle myosin light chain kinase. In contrast, calmodulin remains extended upon binding PhK13. In the presence of both peptides, calmodulin also remains extended. Apparently, the presence of PhK13 inhibits calmodulin from undergoing the PhK5-induced contraction. These data indicate that there is a fundamentally different type of calmodulin-target enzyme interaction in the case of the catalytic subunit of phosphorylase kinase compared with that for myosin light chain kinase

  9. What factors influence uptake of retinal screening among young adults with type 2 diabetes? A qualitative study informed by the theoretical domains framework.

    Science.gov (United States)

    Lake, Amelia J; Browne, Jessica L; Rees, Gwyneth; Speight, Jane

    2017-06-01

    Young adults with type 2 diabetes (T2D, 18-39years) face increased risk of vision loss from diabetic retinopathy (DR). Retinal screening is essential to detect DR, yet screening rates for this group are low and little is known about the underlying factors influencing this important behavior. Using the theoretical domains framework (TDF) to guide data collection and analysis, we explored screening barriers and facilitator, contrasting them with a comparator group of older adults with T2D (40+ years). Thirty semi-structured telephone interviews (10 younger, 20 older adults) were conducted. Data were coded into TDF domains with salience identified by "frequency" of reference. Screening facilitators and barriers were systematically compared between groups. Although many screening facilitators and barriers were shared by younger and older adults, additional factors highly relevant to the former included: social comparison with others ('social influences'); concern for the impact on the family unit, unrealistic optimism and perceived invulnerability ('beliefs about consequences'); lack of time and financial resources ('environmental context and resources'), and DR misconceptions ('knowledge'). This study demonstrated that young adult retinal screening behavior was influenced by additional social cognitive factors compared to older adults, providing a first-step evidence base for clinicians and other health professionals, and potential targets for future eye health and retinal screening interventions. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Text Processing of Domain-Related Information for Individuals with High and Low Domain Knowledge.

    Science.gov (United States)

    Spilich, George J.; And Others

    1979-01-01

    The way in which previously acquired knowledge affects the processing on new domain-related information was investigated. Text processing was studied in two groups differing in knowledge of the domain of baseball. A knowledge structure for the domain was constructed, and text propositions were classified. (SW)

  11. Jahn-teller domains and magnetic domains in Mn2FeO4

    NARCIS (Netherlands)

    Kub, J.; Brabers, V.A.M.; Novák, P.; Gemperle, R.; Simsova, J.

    2000-01-01

    Elastic (Jahn–Teller) domains and magnetic domains in the tetragonal spinel Mn2FeO4 were studied using X-ray double-crystal topography, X-ray diffractometry and the colloid-SEM method. The Jahn–Teller domains of the measured samples are tetragonal with the [0 0 1] c-axis alternating perpendicularly

  12. Supersymmetric domain walls

    NARCIS (Netherlands)

    Bergshoeff, Eric A.; Kleinschmidt, Axel; Riccioni, Fabio

    2012-01-01

    We classify the half-supersymmetric "domain walls," i.e., branes of codimension one, in toroidally compactified IIA/IIB string theory and show to which gauged supergravity theory each of these domain walls belong. We use as input the requirement of supersymmetric Wess-Zumino terms, the properties of

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-03-30

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

  14. Domain wall motion and magnetization reversal processes in a FeSi picture frame single crystal studied by the time-dependent neutron depolarization technique

    International Nuclear Information System (INIS)

    Schaik, F.J. van.

    1979-01-01

    The three dimensional neutron depolarization technique, which gives detailed information about the static properties of ferromagnetic materials, has been extended to a method by means of which the time dependence of magnetic phenomena can be studied. The measurement of the neutron depolarization against time is made possible by applying a periodical magnetic field on the investigated specimen and by continuous sampling of the transmitted neutron intensity in time channels, which are started synchronously with the applied field. The technique has been used in the study of the magnetic domain structure at room temperature of a (010) [001] picture frame FeSi single crystal (3.5 wt.% Si) with outer dimensions of (15 x 10 x 0.26) mm and a frame width of 2.78 mm. (Auth.)

  15. Choroidal thickness in non-ocular Behçet's disease – A spectral-domain OCT study

    Directory of Open Access Journals (Sweden)

    Aman Mittal

    2017-09-01

    Conclusion: This study demonstrates that BD may have subclinical manifestations in the choroid, resulting in thinning of the choroid relative to normal eyes, even without overt signs of ocular involvement.

  16. Observing Privacy, Modesty and Hospitality in the Home Domain: Three Case Studies of Muslim Homes in Brisbane, Australia

    Directory of Open Access Journals (Sweden)

    Zulkeplee Othman

    2014-12-01

    Full Text Available A home embodies a sensorial space that is layered with personal memories and traces of history. The success of a home in providing a strong sense of place depends on various factors such as geographical location, climatic conditions, and occupants’ world-views and perceptions. This paper explores Muslims’ perceptions of privacy, modesty and hospitality within their homes through their lived experiences. This case study focuses on three Muslim families living in Australian designed homes within the same suburb of Brisbane, Australia. The study provides prefatory insight into the ways in which these families perform their daily activities and entertain their guests without jeopardizing their privacy needs. The study examines the significance of modesty in the design of Muslim homes as a means by which family members are able to achieve optimum privacy while simultaneously extending hospitality to guests inside and outside their homes. The findings of this study provide opportunities too, for expanding research into culturally adaptable housing systems to help meet the changing needs of Australian multicultural society.

  17. Homology-modeled ligand-binding domains of medaka estrogen receptors and androgen receptors: A model system for the study of reproduction

    International Nuclear Information System (INIS)

    Cui Jianzhou; Shen Xueyan; Yan Zuowei; Zhao Haobin; Nagahama, Yoshitaka

    2009-01-01

    Estrogen and androgen and their receptors play critical roles in physiological processes such as sexual differentiation and development. Using the available structural models for the human estrogen receptors alpha and beta and androgen receptor as templates, we designed in silico agonist and antagonist models of medaka estrogen receptor (meER) alpha, beta-1, and beta-2, and androgen receptor (meAR) alpha and beta. Using these models, we studied (1) the structural relationship between the ligand-binding domains (LBDs) of ERs and ARs of human and medaka, and (2) whether medaka ER and AR can be potential models for studying the ligand-binding activities of various agonists and antagonists of these receptors by docking analysis. A high level of conservation was observed between the sequences of the ligand-binding domains of meERα and huERα, meERβ1 and huERβ, meERβ2, and huERβ with 62.8%, 66.4%, and 65.1% identity, respectively. The sequence conservation between meARα and huAR, meARβ, and huAR was found with 70.1% and 61.0% of identity, respectively. Thirty-three selected endocrine disrupting chemicals (EDCs), including both agonists and antagonists, were docked into the LBD of ER and AR, and the corresponding docking score for medaka models and human templates were calculated. In order to confirm the conservation of the overall geometry and the binding pocket, the backbone root mean square deviation (RMSD) for Cα atoms was derived from the structure superposition of all 10 medaka homology models to the six human templates. Our results suggested conformational conservation between the ERs and ARs of medaka and human, Thus, medaka could be highly useful as a model system for studies involving estrogen and androgen interaction with their receptors.

  18. Design and implementation of a data acquisition system for the study of dynamics signals in the time Domain

    International Nuclear Information System (INIS)

    Daza, Arnoldo; Hinojosa, Ana; Diaz, Xavier; Neira, Oscar

    2011-01-01

    The purpose of this research was to design and implement a data acquisition system for the study of dynamic signals in the time in order of nanoseconds, through the use of electronic instrumentation to obtain the temporal profiles of light signals, such as pulses of light from a laser or fluorescent light signals. To carry out the design and implementation of the data acquisition system proposed, we used a rapid response transducer and a data acquisition card of high speed. As well, it was developed a graphical user interface for visualization, analysis and study of the data acquired. Thus, it was possible to perform the digitization of a pulse on the order of nanoseconds, as well as the acquisition of fluorescence signals of different wavelengths, from which to obtain theoretical and experimental valuable knowledge based on the physics of spectroscopy.

  19. Covalent Linking Greatly Enhances Photoinduced Electron Transfer in Fullerene-Quantum Dot Nanocomposites: Time-Domain Ab Initio Study

    DEFF Research Database (Denmark)

    Chaban, Vitaly V.; Prezhdo, Victor; Prezhdo, Oleg

    2013-01-01

    , it leads to a notably weaker QD-C-60 interaction than a lengthy molecular bridge. We show that the ET rate in a nonbonded mixture of QDs and C-60 can be enhanced by doping. The photoinduced ET is promoted primarily by mid- and low-frequency vibrations. The study establishes the basic design principles...... for enhancing photoinduced charge separation in nanoscale light harvesting materials....

  20. Study of the nuclear multifragmentation: recent results obtained with the INDRA detector in the intermediate energy domain

    International Nuclear Information System (INIS)

    Saint-Laurent, F.

    1994-01-01

    The new 4π multidetector INDRA, designed for the study of hot nuclear systems decaying by multifragmentation, is available for experiments since the beginning of 1993. First results emphasize its very high detection capabilities. Preliminary results on multiplicity distributions and elemental charge distributions in the most violent collisions for the 36 Ar + 58 Ni and 129 Xe + nat Sn systems are presented. (author) 5 figs., 22 refs

  1. Changes in children's sleep domains between 2 and 3 years of age: the Ulm SPATZ Health Study.

    Science.gov (United States)

    Braig, Stefanie; Urschitz, Michael S; Rothenbacher, Dietrich; Genuneit, Jon

    2017-08-01

    There is growing interest in the link between sleep habits and child health but reference values specific to toddlers as well as longitudinal data on sleep are scarce. We aimed to describe parent-reported child sleep habits and their intra-individual changes in two- to three-year-olds using data from a regional birth cohort study. In the Ulm SPATZ Health Study, a birth cohort study conducted at Ulm, Southern Germany, with baseline examination from April 2012 to May 2013, the German version of the Children's Sleep Habits Questionnaire (CSHQ-DE) was used longitudinally at follow-ups at two and three years (N = 615 children). Descriptive statistics including intra-individual differences between three- and two-year scores were reported, the latter using the sign test. The sample-averaged total and subscale CSHQ scores differed only slightly between two and three years (max. Cohen's d = 0.39). Intra-individual comparisons of the CSHQ subscales or single items revealed congruent but also opposing changes in items belonging to the same subscale. Whereas items on bedtime resistance generally improved, sleep duration shortened with older age. With regard to sleep anxiety, we found worsening in the item 'Afraid of sleeping in the dark' in about one-fifth of our children whereas other items on this CSHQ subscale showed an opposing trend with age. A similar opposing trend was detected within the subscale on night wakings. Our data provide initial descriptive information on sleep habits in toddlers. The high intra-individual changes, partly in opposing directions which may be masked by aggregation, indicate a need for age- and item-specific analyses. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Laboratory study of nitrate photolysis in Antarctic snow. I. Observed quantum yield, domain of photolysis, and secondary chemistry

    DEFF Research Database (Denmark)

    Meusinger, Carl; Berhanu, Tesfaye A.; Erbland, Joseph

    2014-01-01

    undergoing secondary (recombination) chemistry. Modeled NOx emissions may increase significantly above measured values due to the observed quantum yield in this study. The apparent quantum yield in the 200 nm band was found to be ∼ 1%, much lower than reported for aqueous chemistry. A companion paper...... are understood. It has been shown that photolysis of nitrate in the snowpack plays a major role in nitrate loss and that the photolysis products have a significant influence on the local troposphere as well as on other species in the snow. Reported quantum yields for the main reaction spans orders of magnitude...

  3. Cycle studies: material balance estimation in the domain of pressurized water and boiling water reactors. Experimental qualification

    International Nuclear Information System (INIS)

    Chabert, Christine

    1994-01-01

    This study is concerned with the physics of the fuel cycle the aim being to develop and make recommendations concerning schemes for calculating the neutronics of light water reactor fuel cycles. A preliminary study carried out using the old fuel cycle calculation scheme APOLLO1- KAFKA and the library SERMA79 has shown that for the compositions of totally dissolved assemblies from Pressurized Water Reactors (type 17*17) and also for the first time, for Boiling Water Reactor assemblies (type 8*8), the differences between calculation and measurement are large and must be reduced. The integration of the APOLLO2 neutronics code into the fuel cycle calculation scheme improves the results because it can model the situation more precisely. A comparison between APOLLO1 and APOLLO2 using the same options, demonstrated the consistency of the two methods for PWR and BWR geometries. Following this comparison, we developed an optimised scheme for PWR applications using the library CEA86 and the code APOLLO2. Depending on whether the information required is the detailed distribution of the composition of the irradiated fuel or the average composition (estimation of the total material balance of the fuel assembly), the physics options recommended are different. We show that the use of APOLLO2 and the library CEA86 improves the results and especially the estimation of the Pu 239 content. Concerning the Boiling Water Reactor, we have highlighted the need to treat several axial sections of the fuel assembly (variation of the void-fraction, heterogeneity of composition). A scheme using Sn transport theory, permits one to obtain a better coherence between the consumption of U 235 , the production of plutonium and burnup, and a better estimation of the material balance. (author) [fr

  4. A Randomized Controlled ERP Study on the Effects of Multi-Domain Cognitive Training and Task Difficulty on Task Switching Performance in Older Adults

    Science.gov (United States)

    Küper, Kristina; Gajewski, Patrick D.; Frieg, Claudia; Falkenstein, Michael

    2017-01-01

    Executive functions are subject to a marked age-related decline, but have been shown to benefit from cognitive training interventions. As of yet, it is, however, still relatively unclear which neural mechanism can mediate training-related performance gains. In the present electrophysiological study, we examined the effects of multi-domain cognitive training on performance in an untrained cue-based task switch paradigm featuring Stroop color words: participants either had to indicate the word meaning of Stroop stimuli (word task) or perform the more difficult task of color naming (color task). One-hundred and three older adults (>65 years old) were randomly assigned to a training group receiving a 4-month multi-domain cognitive training, a passive no-contact control group or an active (social) control group receiving a 4-month relaxation training. For all groups, we recorded performance and EEG measures before and after the intervention. For the cognitive training group, but not for the two control groups, we observed an increase in response accuracy at posttest, irrespective of task and trial type. No training-related effects on reaction times were found. Cognitive training was also associated with an overall increase in N2 amplitude and a decrease of P2 latency on single trials. Training-related performance gains were thus likely mediated by an enhancement of response selection and improved access to relevant stimulus-response mappings. Additionally, cognitive training was associated with an amplitude decrease in the time window of the target-locked P3 at fronto-central electrodes. An increase in the switch positivity during advance task preparation emerged after both cognitive and relaxation training. Training-related behavioral and event-related potential (ERP) effects were not modulated by task difficulty. The data suggest that cognitive training increased slow negative potentials during target processing which enhanced the N2 and reduced a subsequent P3-like

  5. Data Resource Profile: Cross-national and cross-study sociodemographic and health-related harmonized domains from SAGE plus ELSA, HRS and SHARE (SAGE+, Wave 1).

    Science.gov (United States)

    Minicuci, Nadia; Naidoo, Nirmala; Chatterji, Somnath; Kowal, Paul

    2016-10-01

    Four longitudinal studies were included in this rigorous harmonization process: the Study on global AGEing and adult health (SAGE); English Longitudinal Study on Ageing (ELSA); US Health and Retirement Study (HRS); and Survey of Health, Ageing and Retirement in Europe (SHARE). An ex-post harmonized process was applied to nine health-related thematic domains (socio-demographic and economic, health states, overall self-report of health and mental state, health examinations, physical and mental performance tests, risk factors, chronic conditions, social network and subjective well-being) for data from the 2004 wave of each study. Large samples of adults aged 50 years and older were available from each study: SAGE, n = 18 886; ELSA, n = 9181; HRS, n = 19 303; and SHARE, n = 29 917. The microdata, along with further details about the harmonization process and all metadata, are available through the World Health Organization (WHO) data archive at [http://apps.who.int/healthinfo/systems/surveydata/index.php/catalog]. Further information and enquiries can be made to [sagesurvey@who.int] or the corresponding author. The data resource will continue to be updated with data across additional waves of these surveys and new waves. © The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

  6. Targeting the Cryptococcus neoformans var. grubii Cell Wall Using Lectins: Study of the Carbohydrate-Binding Domain

    Directory of Open Access Journals (Sweden)

    Pamella de Brito Ximenes

    2015-02-01

    Full Text Available Cryptococcus neoformans var. grubii is considered to be the major cause of cryptococcosis in immunosuppressed patients. Understanding cell wall glycoproteins using lectins is of medical interest and can contribute to specific therapy. The aim of this study was to evaluate the carbohydrates on the cell wall of Cryptococcus neoformans var. grubii clinical isolates, using a fluorescein isothiocyanate-lectin binding protocol. Thirty yeast strains stocked in the culture collection were cultivated for 2 days at 30 °C with shaking. Cells were obtained by centrifugation, washed in phosphate-buffered saline, and a suspension of 107 cells/mL was obtained. To determine the binding profile of lectins, concanavalin A (Con A, wheat germ agglutinin (WGA, Ulex europaeus agglutinin I (UEA-I, and peanut agglutinin (PNA conjugated to fluorescein were used. All the tested clinical isolates of Cryptococcus neoformans var. grubii were intensely stained by WGA, moderately stained by Con A, and weakly stained by PNA and UEA-I. Thus, Cryptococcus can be detected in clinical specimens such as blood and cerebrospinal fluid using the fluorescent lectin WGA, which may be considered as an option for detection in cases of suspected cryptococcosis with low laboratory sensitivity. Future applications may be developed using this basic tool.

  7. Direct quantification of PM2.5 fossil and biomass carbon within the Northern Front Range Air Quality Study's domain

    International Nuclear Information System (INIS)

    Klinedinst, D.B.; Currie, L.A.

    1999-01-01

    Radiocarbon ( 14 C) analyses of PM 2.5 (particulate matter with an aerodynamic diameter of 2.5 microm or less) of both ambient and source samples from the Northern Front Range Air Quality Study (NFRAQS) in Colorado were performed. The 14 C analyses were undertaken to provide direct fossil vs modern (biomass) carbon source discrimination data for a subset of summer and winter 1996--1997 samples collected within the Denver metropolitan area. Samples were prepared for 14 C accelerator mass spectrometry measurements using techniques specially developed for small samples, i.e., lt100 μg C. For the days and sampling periods analyzed the median and interquartile range of the winter blank corrected fraction of modern carbon was 23% (16--34%) at Welby and 27% (25--37%) at Brighton. The summer samples exhibited a more mixed signature with a median and interquartile range of 47% (9--70%). Source samples yielded 14 C signatures consistent with expectation. The authors conclude fossil-derived sources contribute substantially in both seasons and at both locations; however, the biomass carbon component dominates episodically in the summer

  8. Study on Relationship between Dielectric Constant and Water Content of Rock-Soil Mixture by Time Domain Reflectometry

    Directory of Open Access Journals (Sweden)

    Daosheng Ling

    2016-01-01

    Full Text Available It is important to test water content of rock-soil mixtures efficiently and accurately to ensure both the quality control of compaction and assessment of the geotechnical engineering properties. To overcome time and energy wastage and probe insertion problems when using the traditional calibration method, a TDR coaxial test tube calibration arrangement using an upward infiltration method was designed. This arrangement was then used to study the influence of dry density, pore fluid conductivity, and soil/rock ratio on the relationship between water content and the dielectric constant of rock-soil mixtures. The results show that the empirical calibration equation forms for rock-soil mixtures can be the same as for soil materials. The effect of dry density on the calibration equation has the most significance and the influence of pore fluid conductivity can be ignored. The impact of variation of the soil/rock ratio can be neutralized by considering the effect of dry density in the calibration equation for the same kind of soil and rock. The empirical equations proposed by Zhao et al. show a good accuracy for rock-soil mixtures, indicating that the TDR method can be used to test gravimetric water content conveniently and efficiently without calibration in the field.

  9. Twin-domain size and bulk oxygen in-diffusion kinetics of YBa2Cu3O6+x studied by neutron powder diffraction and gas volumetry

    DEFF Research Database (Denmark)

    Poulsen, H.F.; Andersen, N.H.; Lebech, B.

    1991-01-01

    which are identified to result from temperature independent twin-domain formation in to different orthorhombic phases with domain sizes 250 and 350 angstrom, respectively. The oxygen in-diffusion flow shows simple relaxation type behaviour J = J0 exp(-t/tau) despite a rather broad particle size...

  10. Structure characterization of the central repetitive domain of high molecular weight gluten proteins .1. Model studies using cyclic and linear peptides

    NARCIS (Netherlands)

    VanDijk, AA; VanWijk, LL; VanVliet, A; Haris, P; VanSwieten, E; Tesser, GI; Robillard, GT

    The high molecular weight (HMW) proteins from wheat contain a repetitive domain that forms 60-80% of their sequence. The consensus peptides PGQGQQ and GYYPTSPQQ form more than 90% of the domain; both are predicted to adopt beta-turn structure. This paper describes the structural characterization of

  11. Conserved Domain Database (CDD)

    Data.gov (United States)

    U.S. Department of Health & Human Services — CDD is a protein annotation resource that consists of a collection of well-annotated multiple sequence alignment models for ancient domains and full-length proteins.

  12. Visualization studies on evidence-based medicine domain knowledge (series 3): visualization for dissemination of evidence based medicine information.

    Science.gov (United States)

    Shen, Jiantong; Yao, Leye; Li, Youping; Clarke, Mike; Gan, Qi; Li, Yifei; Fan, Yi; Gou, Yongchao; Wang, Li

    2011-05-01

    To identify patterns in information sharing between a series of Chinese evidence based medicine (EBM) journals and the Cochrane Database of Systematic Reviews, to determine key evidence dissemination areas for EBM and to provide a scientific basis for improving the dissemination of EBM research. Data were collected on citing and cited from the Chinese Journal of Evidence-Based Medicine (CJEBM), Journal of Evidence-Based Medicine (JEBMc), Chinese Journal of Evidence Based Pediatrics (CJEBP), and the Cochrane Database of Systematic Reviews (CDSR). Relationships between citations were visualized. High-frequency key words from these sources were identified, to build a word co-occurrence matrix and to map research subjects. CDSR contains a large collection of information of relevance to EBM and its contents are widely cited across many journals, suggesting a well-developed citation environment. The content and citation of the Chinese journals have been increasing in recent years. However, their citation environments are much less developed, and there is a wide variation in the breadth and strength of their knowledge communication, with the ranking from highest to lowest being CJEBM, JEBMc and CJEBP. The content of CDSR is almost exclusively Cochrane intervention reviews examining the effects of healthcare interventions, so it's contribution to EBM is mostly in disease control and treatment. On the other hand, the Chinese journals on evidence-based medicine and practice focused more on areas such as education and research, design and quality of clinical trials, evidence based policymaking, evidence based clinical practice, tumor treatment, and pediatrics. Knowledge and findings of EBM are widely communicated and disseminated. However, citation environments and range of knowledge communication differ greatly between the journals examined in this study. This finds that Chinese EBM has focused mainly on clinical medicine, Traditional Chinese Medicine, pediatrics, tumor

  13. Risperidone for the core symptom domains of autism: results from the study by the autism network of the research units on pediatric psychopharmacology.

    Science.gov (United States)

    McDougle, Christopher J; Scahill, Lawrence; Aman, Michael G; McCracken, James T; Tierney, Elaine; Davies, Mark; Arnold, L Eugene; Posey, David J; Martin, Andrès; Ghuman, Jaswinder K; Shah, Bhavik; Chuang, Shirley Z; Swiezy, Naomi B; Gonzalez, Nilda M; Hollway, Jill; Koenig, Kathleen; McGough, James J; Ritz, Louise; Vitiello, Benedetto

    2005-06-01

    Risperidone has been found efficacious for decreasing severe tantrums, aggression, and self-injurious behavior in children and adolescents with autistic disorder (autism). The authors report on whether risperidone improves the core symptoms of autism, social and communication impairment and repetitive and stereotyped behavior. The database from an 8-week double-blind, placebo-controlled trial (N=101) and 16-week open-label continuation study (N=63) of risperidone for children and adolescents with autism was used to test for drug effects on secondary outcome measures: scores on the Ritvo-Freeman Real Life Rating Scale, the Children's Yale-Brown Obsessive Compulsive Scale, and the maladaptive behavior domain of the Vineland Adaptive Behavior Scales. Compared to placebo, risperidone led to a significantly greater reduction in the overall score on the Ritvo-Freeman Real Life Rating Scale, as well as the scores on the subscales for sensory motor behaviors (subscale I), affectual reactions (subscale III), and sensory responses (subscale IV). No statistically significant difference was observed, however, on the subscale for social relatedness (subscale II) or language (subscale V). Risperidone also resulted in significantly greater reductions in scores on the Children's Yale-Brown Obsessive Compulsive Scale and Vineland maladaptive behavior domain. This pattern of treatment response was maintained for 6 months. Risperidone led to significant improvements in the restricted, repetitive, and stereotyped patterns of behavior, interests, and activities of autistic children but did not significantly change their deficit in social interaction and communication. Further research is necessary to develop effective treatments for the core social and communicative impairments of autism.

  14. Experimental Study of Electron and Phonon Dynamics in Nanoscale Materials by Ultrafast Laser Time-Domain Spectroscopy

    Science.gov (United States)

    Shen, Xiaohan

    With the rapid advances in the development of nanotechnology, nowadays, the sizes of elementary unit, i.e. transistor, of micro- and nanoelectronic devices are well deep into nanoscale. For the pursuit of cheaper and faster nanoscale electronic devices, the size of transistors keeps scaling down. As the miniaturization of the nanoelectronic devices, the electrical resistivity increases dramatically, resulting rapid growth in the heat generation. The heat generation and limited thermal dissipation in nanoscale materials have become a critical problem in the development of the next generation nanoelectronic devices. Copper (Cu) is widely used conducting material in nanoelectronic devices, and the electron-phonon scattering is the dominant contributor to the resistivity in Cu nanowires at room temperature. Meanwhile, phonons are the main carriers of heat in insulators, intrinsic and lightly doped semiconductors. The thermal transport is an ensemble of phonon transport, which strongly depends on the phonon frequency. In addition, the phonon transport in nanoscale materials can behave fundamentally different than in bulk materials, because of the spatial confinement. However, the size effect on electron-phonon scattering and frequency dependent phonon transport in nanoscale materials remain largely unexplored, due to the lack of suitable experimental techniques. This thesis is mainly focusing on the study of carrier dynamics and acoustic phonon transport in nanoscale materials. The weak photothermal interaction in Cu makes thermoreflectance measurement difficult, we rather measured the reflectivity change of Cu induced by absorption variation. We have developed a method to separately measure the processes of electron-electron scattering and electron-phonon scattering in epitaxial Cu films by monitoring the transient reflectivity signal using the resonant probe with particular wavelengths. The enhancement on electron-phonon scattering in epitaxial Cu films with thickness

  15. On the domain of the Nelson Hamiltonian

    Science.gov (United States)

    Griesemer, M.; Wünsch, A.

    2018-04-01

    The Nelson Hamiltonian is unitarily equivalent to a Hamiltonian defined through a closed, semibounded quadratic form, the unitary transformation being explicitly known and due to Gross. In this paper, we study the mapping properties of the Gross-transform in order to characterize the regularity properties of vectors in the form domain of the Nelson Hamiltonian. Since the operator domain is a subset of the form domain, our results apply to vectors in the domain of the Hamiltonian as well. This work is a continuation of our previous work on the Fröhlich Hamiltonian.

  16. School grade and sex differences in domain-specific sedentary behaviors among Japanese elementary school children: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Kaori Ishii

    2017-04-01

    Full Text Available Abstract Background It is vital to reduce the proportion of sedentary behavior in children. Understanding the duration and behavioral context is needed. The present study examined school-grade and sex differences in domain-specific sedentary times and concurrence with screen-time guidelines among Japanese elementary school children. Methods A total of 625 children (330 boys were surveyed in 2010 and 2014. Using a questionnaire, data regarding participants’ grade (first through third grades: lower grades; fourth through six grades: higher grades, sex, weight, and height were collected in addition to the time spent per day engaging in each specific sedentary behavior separately: (1 reading or listening to music, (2 TV or video viewing, (3 TV game use, (4 internet use excluding class, (5 homework, and (6 car travel. Two-way analysis of covariance and logistic regression analyses, adjusted for BMI and moderate to vigorous physical activity, were used to examine school-grade and sex differences in sedentary behaviors and the independent risk of exceeding recommended total daily screen time (< 2 h. Results On 625 children, mean minutes (SD of sedentary behavior per week in (1 – (6 were 90.3 (123.4, 535.0 (356.6, 167.3 (222.1, 23.9 (70.9, 264.9 (185.3, and 33.4 (61.2 in weekdays and 42.1 (70.0, 323.9 (232.0, 123.0 (96.4, 15.8 (49.9, 74.4 (96.4, and 71.3 (84.9 in weekends, respectively. There were differences in the minutes of sedentary behavior between participants of 2010 and 2014; e.g., TV game use and homework in weekdays and weekdays and car travel in weekends. Boys spent more time in TV game use, and girls spent more time reading, listening to music, doing homework, and car travel. Higher-grade students spent more time reading or listening to music, using a computer, and doing homework. Higher-grade students were 2.09 times (95% CI: 1.32 − 3.30 in whole week, 2.08 times (95% CI: 1.45 − 3.00 in weekday, and 1.88 times (95% CI: 1.29

  17. Enablers and barriers for women with gestational diabetes mellitus to achieve optimal glycaemic control - a qualitative study using the theoretical domains framework.

    Science.gov (United States)

    Martis, Ruth; Brown, Julie; McAra-Couper, Judith; Crowther, Caroline A

    2018-04-11

    Glycaemic target recommendations vary widely between international professional organisations for women with gestational diabetes mellitus (GDM). Some studies have reported women's experiences of having GDM, but little is known how this relates to their glycaemic targets. The aim of this study was to identify enablers and barriers for women with GDM to achieve optimal glycaemic control. Women with GDM were recruited from two large, geographically different, hospitals in New Zealand to participate in a semi-structured interview to explore their views and experiences focusing on enablers and barriers to achieving optimal glycaemic control. Final thematic analysis was performed using the Theoretical Domains Framework. Sixty women participated in the study. Women reported a shift from their initial negative response to accepting their diagnosis but disliked the constant focus on numbers. Enablers and barriers were categorised into ten domains across the three study questions. Enablers included: the ability to attend group teaching sessions with family and hear from women who have had GDM; easy access to a diabetes dietitian with diet recommendations tailored to a woman's context including ethnic food and financial considerations; free capillary blood glucose (CBG) monitoring equipment, health shuttles to take women to appointments; child care when attending clinic appointments; and being taught CBG testing by a community pharmacist. Barriers included: lack of health information, teaching sessions, consultations, and food diaries in a woman's first language; long waiting times at clinic appointments; seeing a different health professional every clinic visit; inconsistent advice; no tailored physical activities assessments; not knowing where to access appropriate information on the internet; unsupportive partners, families, and workplaces; and unavailability of social media or support groups for women with GDM. Perceived judgement by others led some women only to share

  18. Between-domain relations of students' academic emotions and their judgments of school domain similarity

    Science.gov (United States)

    Goetz, Thomas; Haag, Ludwig; Lipnevich, Anastasiya A.; Keller, Melanie M.; Frenzel, Anne C.; Collier, Antonie P. M.

    2014-01-01

    With the aim to deepen our understanding of the between-domain relations of academic emotions, a series of three studies was conducted. We theorized that between-domain relations of trait (i.e., habitual) emotions reflected students' judgments of domain similarities, whereas between-domain relations of state (i.e., momentary) emotions did not. This supposition was based on the accessibility model of emotional self-report, according to which individuals' beliefs tend to strongly impact trait, but not state emotions. The aim of Study 1 (interviews; N = 40; 8th and 11th graders) was to gather salient characteristics of academic domains from students' perspective. In Study 2 (N = 1709; 8th and 11th graders) the 13 characteristics identified in Study 1 were assessed along with academic emotions in four different domains (mathematics, physics, German, and English) using a questionnaire-based trait assessment. With respect to the same domains, state emotions were assessed in Study 3 (N = 121; 8th and 11th graders) by employing an experience sampling approach. In line with our initial assumptions, between-domain relations of trait but not state academic emotions reflected between-domain relations of domain characteristics. Implications for research and practice are discussed. PMID:25374547

  19. Between-Domain Relations of Students’ Academic Emotions and Their Judgments of School Domain Similarity

    Directory of Open Access Journals (Sweden)

    Thomas eGoetz

    2014-10-01

    Full Text Available With the aim to deepen our understanding of the between-domain relations of academic emotions, a series of three studies was conducted. We theorized that between-domain relations of trait (i.e., habitual emotions reflected students’ judgments of domain similarities, whereas between-domain relations of state (i.e., momentary emotions did not. This supposition was based on the accessibility model of emotional self-report, according to which individuals’ beliefs tend to strongly impact trait, but not state emotions. The aim of Study 1 (interviews; N = 40; 8th and 11th graders was to gather salient characteristics of academic domains from students’ perspective. In Study 2 (N=1709; 8th and 11th graders the 13 characteristics identified in Study 1 were assessed along with academic emotions in four different domains (mathematics, physics, German, and English using a questionnaire-based trait assessment. With respect to the same domains, state emotions were assessed in Study 3 (N = 121; 8th and 11th graders by employing an experience sampling approach. In line with our initial assumptions, between-domain relations of trait but not state academic emotions reflected between-domain relations of domain characteristics. Implications for research and practice are discussed.

  20. Cooperativity in the two-domain arginine kinase from the sea anemone Anthopleura japonicus. II. Evidence from site-directed mutagenesis studies.

    Science.gov (United States)

    Tada, Hiroshi; Suzuki, Tomohiko

    2010-08-01

    The arginine kinase (AK) from the sea anemone Anthopleura japonicus has an unusual two-domain structure (contiguous dimer; denoted by D1-D2). In a previous report, we suggested cooperativity in the contiguous dimer, which may be a result of domain-domain interactions, using MBP-fused enzymes. To further understand this observation, we inserted six-Lys residues into the linker region of the two-domain AK (D1-K6-D2 mutant) using His-tagged enzyme. The dissociation constants, K(a) and K(ia), of the mutant were similar to those of the wild-type enzyme but the catalytic constant, k(cat), was decreased to 28% that of the wild-type, indicating that some of the domain-domain interactions are lost due to the six-Lys insertion. Y68 plays a major role in arginine binding in the catalytic pocket in Limulus AK, and introduction of mutation at the Y68 position virtually abolishes catalytic activity. Thus, the constructed D1(Y68G)-D2 and D1-D2(Y68G) mutants mimic the D1(inactive)-D2(active) and D1(active)-D2(inactive) enzymes, respectively. The k(cat) values of both Y68 mutants were decreased to 13-18% that of the wild-type enzyme, which is much less than the 50% level of the two-domain enzyme. Thus, it is clear that substrate-binding to both domains is necessary for full expression of activity. In other words, substrate-binding appears to act as the trigger of the functional cooperativity in two-domain AK. Copyright 2010 Elsevier B.V. All rights reserved.

  1. Domain-Specific Control of Selective Attention

    Science.gov (United States)

    Lin, Szu-Hung; Yeh, Yei-Yu

    2014-01-01

    Previous research has shown that loading information on working memory affects selective attention. However, whether the load effect on selective attention is domain-general or domain-specific remains unresolved. The domain-general effect refers to the findings that load in one content (e.g. phonological) domain in working memory influences processing in another content (e.g., visuospatial) domain. Attentional control supervises selection regardless of information domain. The domain-specific effect refers to the constraint of influence only when maintenance and processing operate in the same domain. Selective attention operates in a specific content domain. This study is designed to resolve this controversy. Across three experiments, we manipulated the type of representation maintained in working memory and the type of representation upon which the participants must exert control to resolve conflict and select a target into the focus of attention. In Experiments 1a and 1b, participants maintained digits and nonverbalized objects, respectively, in working memory while selecting a target in a letter array. In Experiment 2, we presented auditory digits with a letter flanker task to exclude the involvement of resource competition within the same input modality. In Experiments 3a and 3b, we replaced the letter flanker task with an object flanker task while manipulating the memory load on object and digit representation, respectively. The results consistently showed that memory load modulated distractibility only when the stimuli of the two tasks were represented in the same domain. The magnitude of distractor interference was larger under high load than under low load, reflecting a lower efficacy of information prioritization. When the stimuli of the two tasks were represented in different domains, memory load did not modulate distractibility. Control of processing priority in selective attention demands domain-specific resources. PMID:24866977

  2. Radioimmunotherapy targeting the extra domain B of fibronectin in C6 rat gliomas: a preliminary study about the therapeutic efficacy of iodine-131-labeled SIP(L19)

    International Nuclear Information System (INIS)

    Spaeth, Nicolas; Wyss, Matthias T.; Pahnke, Jens; Biollaz, Gregoire; Trachsel, Eveline; Drandarov, Konstantin; Treyer, Valerie; Weber, Bruno; Neri, Dario; Buck, Alfred

    2006-01-01

    Despite aggressive treatment protocols, patients suffering from glioblastoma multiforme still experience poor outcome. Therefore, new adjuvant therapeutic options such as radioimmunotherapy (RIT) have been studied and have resulted in significant survival benefit. In this study, we assessed the efficacy of a novel radioimmunotherapeutic approach targeting the extra domain B (EDB) of fibronectin, a marker of angiogenesis, in glioma-bearing rats. Methods: C6 gliomas were induced intracerebrally in Wistar rats. Ten to 11 days later, 220-360 MBq of iodine-131-labeled anti-EDB SIP(L19) ('small immunoprotein') was administered intravenously into nine animals, yielding a radiation dose of 13-21 Gy. Another nine rats served as controls. Then the following parameters were compared: median survival time, tumor size and histology. Results: Histological examination of the tumors revealed typical glioblastoma characteristics. Eleven of 18 rats developed a tumor size bigger than 150 mm 3 . When these animals were used for survival analysis, median survival did significantly differ between groups [22 days (therapy; n=7) vs. 16 days (control; n=4); P 131 I-SIP(L19)-RIT showed promising potential in treating C6 gliomas, warranting further studies. However, larger trials with preferentially higher doses are needed to confirm this finding and, potentially, to further increase the efficacy of this treatment

  3. Crystallization and preliminary X-ray diffraction studies of Drosophila melanogaster Gαo-subunit of heterotrimeric G protein in complex with the RGS domain of CG5036

    International Nuclear Information System (INIS)

    Tishchenko, Svetlana; Gabdulkhakov, Azat; Tin, Uliana; Kostareva, Olga; Lin, Chen; Katanaev, Vladimir L.

    2012-01-01

    D. melanogaster Gαo-subunit and the RGS domain of its interacting partner CG5036 have been overproduced and purified; the crystallization and preliminary X-ray crystallographic analysis of the complex of the two proteins are reported. Regulator of G-protein signalling (RGS) proteins negatively regulate heterotrimeric G-protein signalling through their conserved RGS domains. RGS domains act as GTPase-activating proteins, accelerating the GTP hydrolysis rate of the activated form of Gα-subunits. Although omnipresent in eukaryotes, RGS proteins have not been adequately analysed in non-mammalian organisms. The Drosophila melanogaster Gαo-subunit and the RGS domain of its interacting partner CG5036 have been overproduced and purified; the crystallization of the complex of the two proteins using PEG 4000 as a crystallizing agent and preliminary X-ray crystallographic analysis are reported. Diffraction data were collected to 2.0 Å resolution using a synchrotron-radiation source

  4. Studies on micro-domain structure in segmented polyether polyurethane-ureas by positron annihilation lifetime and small-angle X-ray scattering

    International Nuclear Information System (INIS)

    Yin Chuanyuan; Gu Qingchao

    1997-01-01

    The micro-domain structure of segmented polyether polyurethane-ureas is investigated by means of positron annihilation lifetime spectroscopy, small-angle X-ray scattering and differential scanning calorimetry. The experimental results show that the decrease in the domain volume and free volume results from the increase in the hard segment (polyurethane-urea segment) contents as the number-average molecular weight M n -bar of the soft segments (polyethylene glycol segments) is the same, and that the increase in domain volume and free volume result from the increase in the M n -bar of the soft segments when the hard segment content is the same or nearly the same. These results demonstrate that positron annihilation lifetime spectroscopy is a sensitive technique to probe the micro-domain structure in polymers

  5. X-ray crystallographic studies of the extracellular domain of the first plant ATP receptor, DORN1, and the orthologous protein from Camelina sativa

    Energy Technology Data Exchange (ETDEWEB)

    Li, Zhijie; Chakraborty, Sayan; Xu, Guozhou (NCSU)

    2016-10-26

    Does not respond to nucleotides 1 (DORN1) has recently been identified as the first membrane-integral plant ATP receptor, which is required for ATP-induced calcium response, mitogen-activated protein kinase activation and defense responses inArabidopsis thaliana. In order to understand DORN1-mediated ATP sensing and signal transduction, crystallization and preliminary X-ray studies were conducted on the extracellular domain of DORN1 (atDORN1-ECD) and that of an orthologous protein,Camelina sativalectin receptor kinase I.9 (csLecRK-I.9-ECD or csI.9-ECD). A variety of deglycosylation strategies were employed to optimize the glycosylated recombinant atDORN1-ECD for crystallization. In addition, the glycosylated csI.9-ECD protein was crystallized at 291 K. X-ray diffraction data were collected at 4.6 Å resolution from a single crystal. The crystal belonged to space groupC222 orC2221, with unit-cell parametersa= 94.7,b= 191.5,c= 302.8 Å. These preliminary studies have laid the foundation for structural determination of the DORN1 and I.9 receptor proteins, which will lead to a better understanding of the perception and function of extracellular ATP in plants.

  6. Is being resolute better than being pragmatic when it comes to breastfeeding? Longitudinal qualitative study investigating experiences of women intending to breastfeed using the Theoretical Domains Framework.

    Science.gov (United States)

    Jardine, E E; McLellan, J; Dombrowski, S U

    2017-09-01

    In the UK, initiating then discontinuing breastfeeding before two weeks post-partum is common. The aim of this longitudinal qualitative study was to explore which psychosocial factors may influence discontinuation. A sample of 10 pregnant women intending to breastfeed were recruited. A longitudinal qualitative design was used to capture views prior to and two weeks following birth. Semi-structured interviews were conducted underpinned by the Theoretical Domains Framework to explore a comprehensive list of psychosocial factors. Four women discontinued breastfeeding at the time of the second interview. Pre-partum differences were identified between maintainers and discontinuers; discontinuers appeared to have stronger intentions to breastfeed based on their self-determination, self-confidence and perception of fewer barriers to breastfeeding. Post-partum, discontinuers highlighted how they felt physically unable to carry on; their feeding experiences elicited negative emotions and pain. Negative emotions appeared to be exacerbated by original breastfeeding beliefs and advice given by healthcare professionals. The women in this study who discontinued breastfeeding showed less cognitive flexibility, which appeared to exacerbate post-partum emotional distress, when they encountered difficulties. Women with strong intentions and self-determination might benefit from support in anticipating potential barriers and identifying ways of overcoming them. © The Author 2016. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  7. A genetic association study of the FXYD domain containing ion transport regulator 6 (FXYD6) gene, encoding phosphohippolin, in susceptibility to schizophrenia in a Japanese population.

    Science.gov (United States)

    Ito, Yoshihito; Nakamura, Yukako; Takahashi, Nagahide; Saito, Shinichi; Aleksic, Branko; Iwata, Nakao; Inada, Toshiya; Ozaki, Norio

    2008-06-13

    The FXYD domain containing ion transport regulator 6 (FXYD6) gene is located within a region of chromosome 11 (11q23.3) that has been shown by a number of genome scans to be one of the most well-established linkages to schizophrenia. FXYD6 encodes the protein phosphohippolin, which is primar