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Sample records for hinge domain highlight

  1. Encephalomyocarditis virus Leader protein hinge domain is responsible for interactions with Ran GTPase

    Energy Technology Data Exchange (ETDEWEB)

    Bacot-Davis, Valjean R., E-mail: bacotdavis@wisc.edu [Institute for Molecular Virology, University of Wisconsin-Madison, R.M. Bock Laboratories, 1525 Linden Dr. Madison, WI 53706 (United States); Palmenberg, Ann C., E-mail: acpalmen@wisc.edu [Institute for Molecular Virology, University of Wisconsin-Madison, R.M. Bock Laboratories, 1525 Linden Dr. Madison, WI 53706 (United States); Department of Biochemistry, University of Wisconsin-Madison, R.M. Bock Laboratories, 1525 Linden Dr. Madison, WI 53706 (United States)

    2013-08-15

    Encephalomyocarditis virus (EMCV), a Cardiovirus, initiates its polyprotein with a short 67 amino acid Leader (L) sequence. The protein acts as a unique pathogenicity factor, with anti-host activities which include the triggering of nuclear pore complex hyperphosphorylation and direct binding inhibition of the active cellular transport protein, Ran GTPase. Chemical modifications and protein mutagenesis now map the Ran binding domain to the L hinge-linker region, and in particular, to amino acids 35–40. Large deletions affecting this region were shown previously to diminish Ran binding. New point mutations, especially K35Q, D37A and W40A, preserve the intact L structure, abolish Ran binding and are deficient for nucleoporin (Nup) hyperphosphorylation. Ran itself morphs through multiple configurations, but reacts most effectively with L when in the GDP format, preferably with an empty nucleotide binding pocket. Therefore, L:Ran binding, mediated by the linker-hinge, is a required step in L-induced nuclear transport inhibition. - Highlights: • The hinge domain provides critical residues in Cardiovirus L:Ran complex formation. • Leader prefers to bind Ran in a nucleotide free, GDP-conformation. • L-induced Nup62 phosphorylation is reduced with Ran-deficient binding mutations.

  2. Incorporation of a hinge domain improves the expansion of chimeric antigen receptor T cells

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    Le Qin

    2017-03-01

    Full Text Available Abstract Background Multiple iterations of chimeric antigen receptors (CARs have been developed, mainly focusing on intracellular signaling modules. However, the effect of non-signaling extracellular modules on the expansion and therapeutic efficacy of CARs remains largely undefined. Methods We generated two versions of CAR vectors, with or without a hinge domain, targeting CD19, mesothelin, PSCA, MUC1, and HER2, respectively. Then, we systematically compared the effect of the hinge domains on the growth kinetics, cytokine production, and cytotoxicity of CAR T cells in vitro and in vivo. Results During in vitro culture period, the percentages and absolute numbers of T cells expressing the CARs containing a hinge domain continuously increased, mainly through the promotion of CD4+ CAR T cell expansion, regardless of the single-chain variable fragment (scFv. In vitro migration assay showed that the hinges enhanced CAR T cells migratory capacity. The T cells expressing anti-CD19 CARs with or without a hinge had similar antitumor capacities in vivo, whereas the T cells expressing anti-mesothelin CARs containing a hinge domain showed enhanced antitumor activities. Conclusions Hence, our results demonstrate that a hinge contributes to CAR T cell expansion and is capable of increasing the antitumor efficacy of some specific CAR T cells. Our results suggest potential novel strategies in CAR vector design.

  3. Is Domain Highlighting Actually Helpful in Identifying Phishing Web Pages?

    Science.gov (United States)

    Xiong, Aiping; Proctor, Robert W; Yang, Weining; Li, Ninghui

    2017-06-01

    To evaluate the effectiveness of domain highlighting in helping users identify whether Web pages are legitimate or spurious. As a component of the URL, a domain name can be overlooked. Consequently, browsers highlight the domain name to help users identify which Web site they are visiting. Nevertheless, few studies have assessed the effectiveness of domain highlighting, and the only formal study confounded highlighting with instructions to look at the address bar. We conducted two phishing detection experiments. Experiment 1 was run online: Participants judged the legitimacy of Web pages in two phases. In Phase 1, participants were to judge the legitimacy based on any information on the Web page, whereas in Phase 2, they were to focus on the address bar. Whether the domain was highlighted was also varied. Experiment 2 was conducted similarly but with participants in a laboratory setting, which allowed tracking of fixations. Participants differentiated the legitimate and fraudulent Web pages better than chance. There was some benefit of attending to the address bar, but domain highlighting did not provide effective protection against phishing attacks. Analysis of eye-gaze fixation measures was in agreement with the task performance, but heat-map results revealed that participants' visual attention was attracted by the highlighted domains. Failure to detect many fraudulent Web pages even when the domain was highlighted implies that users lacked knowledge of Web page security cues or how to use those cues. Potential applications include development of phishing prevention training incorporating domain highlighting with other methods to help users identify phishing Web pages.

  4. Concrete Hinges

    DEFF Research Database (Denmark)

    Halding, Philip Skov; Hertz, Kristian Dahl; Schmidt, Jacob Wittrup

    2014-01-01

    In the first part of the 20th century concrete hinges developed by Freyssinet and Mesnager were widely tested and implemented in concrete structures. The concrete hinges were used a great deal in closed-spandrel arch bridges. Since such a bridge type has not been competitive for the past 40 years......, the research in concrete hinges has not evolved significantly in that period. But introducing a new state-of-the-art concrete arch bridge solution (Pearl-Chain arches invented at the Technical University of Denmark) creates a necessity of a concrete hinge research based on modern standards. Back when research...... in concrete hinges was more common different designs were proposed for the geometry and reinforcement. Previous research focused on fatigue, multi-axial stresses around the hinge throat, and the relation between rotation- and moment. But many different test-setups were proposed by different researchers...

  5. Shape Memory Composite Hybrid Hinge

    Science.gov (United States)

    Fang, Houfei; Im, Eastwood; Lin, John; Scarborough, Stephen

    2012-01-01

    There are two conventional types of hinges for in-space deployment applications. The first type is mechanically deploying hinges. A typical mechanically deploying hinge is usually composed of several tens of components. It is complicated, heavy, and bulky. More components imply higher deployment failure probability. Due to the existence of relatively moving components among a mechanically deploying hinge, it unavoidably has microdynamic problems. The second type of conventional hinge relies on strain energy for deployment. A tape-spring hinge is a typical strain energy hinge. A fundamental problem of a strain energy hinge is that its deployment dynamic is uncontrollable. Usually, its deployment is associated with a large impact, which is unacceptable for many space applications. Some damping technologies have been experimented with to reduce the impact, but they increased the risks of an unsuccessful deployment. Coalescing strain energy components with shape memory composite (SMC) components to form a hybrid hinge is the solution. SMCs are well suited for deployable structures. A SMC is created from a high-performance fiber and a shape memory polymer resin. When the resin is heated to above its glass transition temperature, the composite becomes flexible and can be folded or packed. Once cooled to below the glass transition temperature, the composite remains in the packed state. When the structure is ready to be deployed, the SMC component is reheated to above the glass transition temperature, and it returns to its as-fabricated shape. A hybrid hinge is composed of two strain energy flanges (also called tape-springs) and one SMC tube. Two folding lines are placed on the SMC tube to avoid excessive strain on the SMC during folding. Two adapters are used to connect the hybrid hinge to its adjacent structural components. While the SMC tube is heated to above its glass transition temperature, a hybrid hinge can be folded and stays at folded status after the temperature

  6. Intensive mutagenesis of the nisin hinge leads to the rational design of enhanced derivatives.

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    Brian Healy

    Full Text Available Nisin A is the most extensively studied lantibiotic and has been used as a preservative by the food industry since 1953. This 34 amino acid peptide contains three dehydrated amino acids and five thioether rings. These rings, resulting from one lanthionine and four methyllanthionine bridges, confer the peptide with its unique structure. Nisin A has two mechanisms of action, with the N-terminal domain of the peptide inhibiting cell wall synthesis through lipid II binding and the C-terminal domain responsible for pore-formation. The focus of this study is the three amino acid 'hinge' region (N 20, M 21 and K 22 which separates these two domains and allows for conformational flexibility. As all lantibiotics are gene encoded, novel variants can be generated through manipulation of the corresponding gene. A number of derivatives in which the hinge region was altered have previously been shown to possess enhanced antimicrobial activity. Here we take this approach further by employing simultaneous, indiscriminate site-saturation mutagenesis of all three hinge residues to create a novel bank of nisin derivative producers. Screening of this bank revealed that producers of peptides with hinge regions consisting of AAK, NAI and SLS displayed enhanced bioactivity against a variety of targets. These and other results suggested a preference for small, chiral amino acids within the hinge region, leading to the design and creation of producers of peptides with hinges consisting of AAA and SAA. These producers, and the corresponding peptides, exhibited enhanced bioactivity against Lactococcus lactis HP, Streptococcus agalactiae ATCC 13813, Mycobacterium smegmatis MC2155 and Staphylococcus aureus RF122 and thus represent the first example of nisin derivatives that possess enhanced activity as a consequence of rational design.

  7. Roles of the β subunit hinge domain in ATP synthase F1 sector: Hydrophobic network formed by introduced βPhe174 inhibits subunit rotation

    International Nuclear Information System (INIS)

    Nakanishi-Matsui, Mayumi; Kashiwagi, Sachiko; Kojima, Masaki; Nonaka, Takamasa; Futai, Masamitsu

    2010-01-01

    The ATP synthase β subunit hinge domain (βPhe148 ∼ βGly186, P-loop/α-helixB/loop/β-sheet4, Escherichia coli residue numbering) dramatically changes in conformation upon nucleotide binding. We previously reported that F 1 with the βSer174 to Phe mutation in the domain lowered the γ subunit rotation speed, and thus decreased the ATPase activity [M. Nakanishi-Matsui, S. Kashiwagi, T. Ubukata, A. Iwamoto-Kihara, Y. Wada, M. Futai, Rotational catalysis of Escherichia coli ATP synthase F 1 sector. Stochastic fluctuation and a key domain of the β subunit, J. Biol. Chem. 282 (2007) 20698-20704.]. Homology modeling indicates that the amino acid replacement induces a hydrophobic network, in which the βMet159, βIle163, and βAla167 residues of the β subunit are involved together with the mutant βPhe174. The network is expected to stabilize the conformation of β DP (nucleotide-bound form of the β subunit), resulting in increased activation energy for transition to β E (empty β subunit). The modeling further predicts that replacement of βMet159 with Ala or Ile weakens the hydrophobic network. As expected, these two mutations experimentally suppressed the ATPase activities as well as subunit rotation of βS174F. Furthermore, the rotation rate decreased with the increase of the strength in the hydrophobic network. These results indicate that the smooth conformational change of the β subunit hinge domain is pertinent for the rotational catalysis.

  8. The SH2 Domain Regulates c-Abl Kinase Activation by a Cyclin-Like Mechanism and Remodulation of the Hinge Motion

    Science.gov (United States)

    Dölker, Nicole; Górna, Maria W.; Sutto, Ludovico; Torralba, Antonio S.; Superti-Furga, Giulio; Gervasio, Francesco L.

    2014-01-01

    Regulation of the c-Abl (ABL1) tyrosine kinase is important because of its role in cellular signaling, and its relevance in the leukemiogenic counterpart (BCR-ABL). Both auto-inhibition and full activation of c-Abl are regulated by the interaction of the catalytic domain with the Src Homology 2 (SH2) domain. The mechanism by which this interaction enhances catalysis is not known. We combined computational simulations with mutagenesis and functional analysis to find that the SH2 domain conveys both local and global effects on the dynamics of the catalytic domain. Locally, it regulates the flexibility of the αC helix in a fashion reminiscent of cyclins in cyclin-dependent kinases, reorienting catalytically important motifs. At a more global level, SH2 binding redirects the hinge motion of the N and C lobes and changes the conformational equilibrium of the activation loop. The complex network of subtle structural shifts that link the SH2 domain with the activation loop and the active site may be partially conserved with other SH2-domain containing kinases and therefore offer additional parameters for the design of conformation-specific inhibitors. PMID:25299346

  9. The SH2 domain regulates c-Abl kinase activation by a cyclin-like mechanism and remodulation of the hinge motion.

    Science.gov (United States)

    Dölker, Nicole; Górna, Maria W; Sutto, Ludovico; Torralba, Antonio S; Superti-Furga, Giulio; Gervasio, Francesco L

    2014-10-01

    Regulation of the c-Abl (ABL1) tyrosine kinase is important because of its role in cellular signaling, and its relevance in the leukemiogenic counterpart (BCR-ABL). Both auto-inhibition and full activation of c-Abl are regulated by the interaction of the catalytic domain with the Src Homology 2 (SH2) domain. The mechanism by which this interaction enhances catalysis is not known. We combined computational simulations with mutagenesis and functional analysis to find that the SH2 domain conveys both local and global effects on the dynamics of the catalytic domain. Locally, it regulates the flexibility of the αC helix in a fashion reminiscent of cyclins in cyclin-dependent kinases, reorienting catalytically important motifs. At a more global level, SH2 binding redirects the hinge motion of the N and C lobes and changes the conformational equilibrium of the activation loop. The complex network of subtle structural shifts that link the SH2 domain with the activation loop and the active site may be partially conserved with other SH2-domain containing kinases and therefore offer additional parameters for the design of conformation-specific inhibitors.

  10. The SH2 domain regulates c-Abl kinase activation by a cyclin-like mechanism and remodulation of the hinge motion.

    Directory of Open Access Journals (Sweden)

    Nicole Dölker

    2014-10-01

    Full Text Available Regulation of the c-Abl (ABL1 tyrosine kinase is important because of its role in cellular signaling, and its relevance in the leukemiogenic counterpart (BCR-ABL. Both auto-inhibition and full activation of c-Abl are regulated by the interaction of the catalytic domain with the Src Homology 2 (SH2 domain. The mechanism by which this interaction enhances catalysis is not known. We combined computational simulations with mutagenesis and functional analysis to find that the SH2 domain conveys both local and global effects on the dynamics of the catalytic domain. Locally, it regulates the flexibility of the αC helix in a fashion reminiscent of cyclins in cyclin-dependent kinases, reorienting catalytically important motifs. At a more global level, SH2 binding redirects the hinge motion of the N and C lobes and changes the conformational equilibrium of the activation loop. The complex network of subtle structural shifts that link the SH2 domain with the activation loop and the active site may be partially conserved with other SH2-domain containing kinases and therefore offer additional parameters for the design of conformation-specific inhibitors.

  11. The polyproline site in hinge 2 influences the functional capacity of truncated dystrophins.

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    Glen B Banks

    2010-05-01

    Full Text Available Mutations in dystrophin can lead to Duchenne muscular dystrophy or the more mild form of the disease, Becker muscular dystrophy. The hinge 3 region in the rod domain of dystrophin is particularly prone to deletion mutations. In-frame deletions of hinge 3 are predicted to lead to BMD, however the severity of disease can vary considerably. Here we performed extensive structure-function analyses of truncated dystrophins with modified hinges and spectrin-like repeats in mdx mice. We found that the polyproline site in hinge 2 profoundly influences the functional capacity of a microdystrophin(DeltaR4-R23/DeltaCT with a large deletion in the hinge 3 region. Inclusion of polyproline in microdystrophin(DeltaR4-R23/DeltaCT led to small myofibers (12% smaller than wild-type, Achilles myotendinous disruption, ringed fibers, and aberrant neuromuscular junctions in the mdx gastrocnemius muscles. Replacing hinge 2 of microdystrophin(DeltaR4-R23/DeltaCT with hinge 3 significantly improved the functional capacity to prevent muscle degeneration, increase muscle fiber area, and maintain the junctions. We conclude that the rigid alpha-helical structure of the polyproline site significantly impairs the functional capacity of truncated dystrophins to maintain appropriate connections between the cytoskeleton and extracellular matrix.

  12. Alternative S2 Hinge Regions of the Myosin Rod Affect Myofibrillar Structure and Myosin Kinetics

    Energy Technology Data Exchange (ETDEWEB)

    Miller, Mark S.; Dambacher, Corey M.; Knowles, Aileen F.; Braddock, Joan M.; Farman, Gerrie P.; Irving, Thomas C.; Swank, Douglas M.; Bernstein, Sanford I.; Maughan, David W.; (RPI); (IIT); (SDSU); (Vermont)

    2009-07-01

    The subfragment 2/light meromyosin 'hinge' region has been proposed to significantly contribute to muscle contraction force and/or speed. Transgenic replacement of the endogenous fast muscle isovariant hinge A (exon 15a) in Drosophila melanogaster indirect flight muscle with the slow muscle hinge B (exon 15b) allows examination of the structural and functional changes when only this region of the myosin molecule is different. Hinge B was previously shown to increase myosin rod length, increase A-band and sarcomere length, and decrease flight performance compared to hinge A. We applied additional measures to these transgenic lines to further evaluate the consequences of modifying this hinge region. Structurally, the longer A-band and sarcomere lengths found in the hinge B myofibrils appear to be due to the longitudinal addition of myosin heads. Functionally, hinge B, although a significant distance from the myosin catalytic domain, alters myosin kinetics in a manner consistent with this region increasing myosin rod length. These structural and functional changes combine to decrease whole fly wing-beat frequency and flight performance. Our results indicate that this hinge region plays an important role in determining myosin kinetics and in regulating thick and thin filament lengths as well as sarcomere length.

  13. The Hinge Segment of Human NADPH-Cytochrome P450 Reductase in Conformational Switching: The Critical Role of Ionic Strength

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    Diana Campelo

    2017-10-01

    Full Text Available NADPH-cytochrome P450 reductase (CPR is a redox partner of microsomal cytochromes P450 and is a prototype of the diflavin reductase family. CPR contains 3 distinct functional domains: a FMN-binding domain (acceptor reduction, a linker (hinge, and a connecting/FAD domain (NADPH oxidation. It has been demonstrated that the mechanism of CPR exhibits an important step in which it switches from a compact, closed conformation (locked state to an ensemble of open conformations (unlocked state, the latter enabling electron transfer to redox partners. The conformational equilibrium between the locked and unlocked states has been shown to be highly dependent on ionic strength, reinforcing the hypothesis of the presence of critical salt interactions at the interface between the FMN and connecting FAD domains. Here we show that specific residues of the hinge segment are important in the control of the conformational equilibrium of CPR. We constructed six single mutants and two double mutants of the human CPR, targeting residues G240, S243, I245 and R246 of the hinge segment, with the aim of modifying the flexibility or the potential ionic interactions of the hinge segment. We measured the reduction of cytochrome c at various salt concentrations of these 8 mutants, either in the soluble or membrane-bound form of human CPR. All mutants were found capable of reducing cytochrome c yet with different efficiency and their maximal rates of cytochrome c reduction were shifted to lower salt concentration. In particular, residue R246 seems to play a key role in a salt bridge network present at the interface of the hinge and the connecting domain. Interestingly, the effects of mutations, although similar, demonstrated specific differences when present in the soluble or membrane-bound context. Our results demonstrate that the electrostatic and flexibility properties of the hinge segment are critical for electron transfer from CPR to its redox partners.

  14. Native Alanine Substitution in the Glycine Hinge Modulates Conformational Flexibility of Heme Nitric Oxide/Oxygen (H-NOX) Sensing Proteins.

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    Hespen, Charles W; Bruegger, Joel J; Guo, Yirui; Marletta, Michael A

    2018-06-15

    Heme nitric oxide/oxygen sensing (H-NOX) domains are direct NO sensors that regulate a variety of biological functions in both bacteria and eukaryotes. Previous work on H-NOX proteins has shown that upon NO binding, a conformational change occurs along two glycine residues on adjacent helices (termed the glycine hinge). Despite the apparent importance of the glycine hinge, it is not fully conserved in all H-NOX domains. Several H-NOX sensors from the family Flavobacteriaceae contain a native alanine substitution in one of the hinge residues. In this work, the effect of the increased steric bulk within the Ala-Gly hinge on H-NOX function was investigated. The hinge in Kordia algicida OT-1 ( Ka H-NOX) is composed of A71 and G145. Ligand-binding properties and signaling function for this H-NOX were characterized. The variant A71G was designed to convert the hinge region of Ka H-NOX to the typical Gly-Gly motif. In activity assays with its cognate histidine kinase (HnoK), the wild type displayed increased signal specificity compared to A71G. Increasing titrations of unliganded A71G gradually inhibits HnoK autophosphorylation, while increasing titrations of unliganded wild type H-NOX does not inhibit HnoK. Crystal structures of both wild type and A71G Ka H-NOX were solved to 1.9 and 1.6 Å, respectively. Regions of H-NOX domains previously identified as involved in protein-protein interactions with HnoK display significantly higher b-factors in A71G compared to wild-type H-NOX. Both biochemical and structural data indicate that the hinge region controls overall conformational flexibility of the H-NOX, affecting NO complex formation and regulation of its HnoK.

  15. Non-equivalent role of TM2 gating hinges in heteromeric Kir4.1/Kir5.1 potassium channels.

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    Shang, Lijun; Tucker, Stephen J

    2008-02-01

    Comparison of the crystal structures of the KcsA and MthK potassium channels suggests that the process of opening a K(+) channel involves pivoted bending of the inner pore-lining helices at a highly conserved glycine residue. This bending motion is proposed to splay the transmembrane domains outwards to widen the gate at the "helix-bundle crossing". However, in the inwardly rectifying (Kir) potassium channel family, the role of this "hinge" residue in the second transmembrane domain (TM2) and that of another putative glycine gating hinge at the base of TM2 remain controversial. We investigated the role of these two positions in heteromeric Kir4.1/Kir5.1 channels, which are unique amongst Kir channels in that both subunits lack a conserved glycine at the upper hinge position. Contrary to the effect seen in other channels, increasing the potential flexibility of TM2 by glycine substitutions at the upper hinge position decreases channel opening. Furthermore, the contribution of the Kir4.1 subunit to this process is dominant compared to Kir5.1, demonstrating a non-equivalent contribution of these two subunits to the gating process. A homology model of heteromeric Kir4.1/Kir5.1 shows that these upper "hinge" residues are in close contact with the base of the pore alpha-helix that supports the selectivity filter. Our results also indicate that the highly conserved glycine at the "lower" gating hinge position is required for tight packing of the TM2 helices at the helix-bundle crossing, rather than acting as a hinge residue.

  16. Extended hormone binding site of the human thyroid stimulating hormone receptor: distinctive acidic residues in the hinge region are involved in bovine thyroid stimulating hormone binding and receptor activation.

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    Mueller, Sandra; Kleinau, Gunnar; Jaeschke, Holger; Paschke, Ralf; Krause, Gerd

    2008-06-27

    The human thyroid stimulating hormone receptor (hTSHR) belongs to the glycoprotein hormone receptors that bind the hormones at their large extracellular domain. The extracellular hinge region of the TSHR connects the N-terminal leucine-rich repeat domain with the membrane-spanning serpentine domain. From previous studies we reasoned that apart from hormone binding at the leucine-rich repeat domain, additional multiple hormone contacts might exist at the hinge region of the TSHR by complementary charge-charge recognition. Here we investigated highly conserved charged residues in the hinge region of the TSHR by site-directed mutagenesis to identify amino acids interacting with bovine TSH (bTSH). Indeed, the residues Glu-297, Glu-303, and Asp-382 in the TSHR hinge region are essential for bTSH binding and partially for signal transduction. Side chain substitutions showed that the negative charge of Glu-297 and Asp-382 is necessary for recognition of bTSH by the hTSHR. Multiple combinations of alanine mutants of the identified positions revealed an increased negative effect on hormone binding. An assembled model suggests that the deciphered acidic residues form negatively charged patches at the hinge region resulting in an extended binding mode for bTSH on the hTSHR. Our data indicate that certain positively charged residues of bTSH might be involved in interaction with the identified negatively charged amino acids of the hTSHR hinge region. We demonstrate that the hinge region represents an extracellular intermediate connector for both hormone binding and signal transduction of the hTSHR.

  17. Hinge(ga) Brand - tõhusaim relv mõrtsukate ja varaste vastu / Hinge Brand ; interv. Kaarel Kressa

    Index Scriptorium Estoniae

    Brand, Hinge, 1940-2007

    2006-01-01

    Intervjuu 40 aastat prokuröriametit pidanud ja pensionile siirduva Hinge Brandiga. Lisatud: Hinge Brandi CV ning Põhja ringkonnaprokuratuuri erisasjade prokuröri Jüri Kasesalu, siseministeeriumi arendusjuhi Lauri Taburi ja keskkriminaalpolitsei politseijuhtivinspektori Margus Maasepa kommentaarid

  18. Reliability evaluation for hinges of folder devices using ESPI

    International Nuclear Information System (INIS)

    Lee, Tae Hun; Chang, Seok Weon; Jhang, Kyung Young

    2004-01-01

    Folder type electronic devices have hinge to support the rotational motion of folder. This hinge is stressed by the rotational inertia moment of folder at the maximum open limit position of folder. This stress is repeated whenever the folder is open, and it is a cause of hinge fracture. In this paper, the reliability evaluation for the hinge fracture in the folder type cellular phone is discussed. For this, the durability testing machine using crack-rocker mechanism is developed to evaluate the life cycle of the hinge, and the degradation after repetitions of opening and shutting is evaluated from the deformation around the hinge, where the deformation is measured by ESPI (electronic speckle pattern interferometer). Experimental results showed that ESPI was able to measure the deformation of hinge precisely, so we could monitor the change of deformation around the hinge as the repetition number of folder open is increased.

  19. A generalized allosteric mechanism for cis-regulated cyclic nucleotide binding domains.

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    Alexandr P Kornev

    2008-04-01

    Full Text Available Cyclic nucleotides (cAMP and cGMP regulate multiple intracellular processes and are thus of a great general interest for molecular and structural biologists. To study the allosteric mechanism of different cyclic nucleotide binding (CNB domains, we compared cAMP-bound and cAMP-free structures (PKA, Epac, and two ionic channels using a new bioinformatics method: local spatial pattern alignment. Our analysis highlights four major conserved structural motifs: 1 the phosphate binding cassette (PBC, which binds the cAMP ribose-phosphate, 2 the "hinge," a flexible helix, which contacts the PBC, 3 the beta(2,3 loop, which provides precise positioning of an invariant arginine from the PBC, and 4 a conserved structural element consisting of an N-terminal helix, an eight residue loop and the A-helix (N3A-motif. The PBC and the hinge were included in the previously reported allosteric model, whereas the definition of the beta(2,3 loop and the N3A-motif as conserved elements is novel. The N3A-motif is found in all cis-regulated CNB domains, and we present a model for an allosteric mechanism in these domains. Catabolite gene activator protein (CAP represents a trans-regulated CNB domain family: it does not contain the N3A-motif, and its long range allosteric interactions are substantially different from the cis-regulated CNB domains.

  20. Differences in Signal Activation by LH and hCG are Mediated by the LH/CG Receptor's Extracellular Hinge Region.

    Science.gov (United States)

    Grzesik, Paul; Kreuchwig, Annika; Rutz, Claudia; Furkert, Jens; Wiesner, Burkhard; Schuelein, Ralf; Kleinau, Gunnar; Gromoll, Joerg; Krause, Gerd

    2015-01-01

    The human lutropin (hLH)/choriogonadotropin (hCG) receptor (LHCGR) can be activated by binding two slightly different gonadotropic glycoprotein hormones, choriogonadotropin (CG) - secreted by the placenta, and lutropin (LH) - produced by the pituitary. They induce different signaling profiles at the LHCGR. This cannot be explained by binding to the receptor's leucine-rich-repeat domain (LRRD), as this binding is similar for the two hormones. We therefore speculate that there are previously unknown differences in the hormone/receptor interaction at the extracellular hinge region, which might help to understand functional differences between the two hormones. We have therefore performed a detailed study of the binding and action of LH and CG at the LHCGR hinge region. We focused on a primate-specific additional exon in the hinge region, which is located between LRRD and the serpentine domain. The segment of the hinge region encoded by exon10 was previously reported to be only relevant to hLH signaling, as the exon10-deletion receptor exhibits decreased hLH signaling, but unchanged hCG signaling. We designed an advanced homology model of the hormone/LHCGR complex, followed by experimental characterization of relevant fragments in the hinge region. In addition, we examined predictions of a helical exon10-encoded conformation by block-wise polyalanine (helix supporting) mutations. These helix preserving modifications showed no effect on hormone-induced signaling. However, introduction of a structure-disturbing double-proline mutant LHCGR-Q303P/E305P within the exon10-helix has, in contrast to exon10-deletion, no impact on hLH, but only on hCG signaling. This opposite effect on signaling by hLH and hCG can be explained by distinct sites of hormone interaction in the hinge region. In conclusion, our analysis provides details of the differences between hLH- and hCG-induced signaling that are mainly determined in the L2-beta loop of the hormones and in the hinge

  1. Differences in signal activation by LH and hCG are mediated by the LH/CG receptor`s extracellular hinge region

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    Paul eGrzesik

    2015-09-01

    Full Text Available The human lutropin/choriogonadotropin receptor (LHCGR can be activated by binding two slightly different gonadotropic glycoprotein hormones, choriogonadotropin (CG - secreted by the placenta, and lutropin (LH - produced by the pituitary. They induce different signaling profiles at the LHCGR. This cannot be explained by binding to the receptor's leucine-rich repeat domain (LRRD, as this binding is similar for the two hormones. We therefore speculate that there are previously unknown differences in the hormone/receptor interaction at the extracellular hinge region, which might help to understand functional differences between the two hormones. We have therefore performed a detailed study of the binding and action of LH and CG at the LHCGR hinge region. We focused on a primate-specific additional exon in the hinge region, which is located between LRRD and the serpentine domain. The segment of the hinge region encoded by exon10 was previously reported to be only relevant to hLH signaling, as the exon10-deletion receptor exhibits decreased hLH signaling, but unchanged hCG signaling. We designed an advanced homology model of the hormone/LHCGR complex, followed by experimental characterization of relevant fragments in the hinge region. In addition, we examined predictions of a helical exon10-encoded conformation by block-wise polyalanine (helix supporting mutations. These helix preserving modifications showed no effect on hormone induced signaling. However, introduction of a structure-disturbing double-proline mutant LHCGR-Q303P/E305P within the exon10-helix has, in contrast to exon10 deletion, no impact on hLH, but only on hCG signaling. This opposite effect on signaling by hLH and hCG can be explained by distinct sites of hormone interaction in the hinge region s. In conclusion, our analysis provides details of the differences between hLH- and hCG-induced signaling that are mainly determined in the L2-beta loop of the hormones and in the hinge region

  2. Differences in Signal Activation by LH and hCG are Mediated by the LH/CG Receptor’s Extracellular Hinge Region

    Science.gov (United States)

    Grzesik, Paul; Kreuchwig, Annika; Rutz, Claudia; Furkert, Jens; Wiesner, Burkhard; Schuelein, Ralf; Kleinau, Gunnar; Gromoll, Joerg; Krause, Gerd

    2015-01-01

    The human lutropin (hLH)/choriogonadotropin (hCG) receptor (LHCGR) can be activated by binding two slightly different gonadotropic glycoprotein hormones, choriogonadotropin (CG) – secreted by the placenta, and lutropin (LH) – produced by the pituitary. They induce different signaling profiles at the LHCGR. This cannot be explained by binding to the receptor’s leucine-rich-repeat domain (LRRD), as this binding is similar for the two hormones. We therefore speculate that there are previously unknown differences in the hormone/receptor interaction at the extracellular hinge region, which might help to understand functional differences between the two hormones. We have therefore performed a detailed study of the binding and action of LH and CG at the LHCGR hinge region. We focused on a primate-specific additional exon in the hinge region, which is located between LRRD and the serpentine domain. The segment of the hinge region encoded by exon10 was previously reported to be only relevant to hLH signaling, as the exon10-deletion receptor exhibits decreased hLH signaling, but unchanged hCG signaling. We designed an advanced homology model of the hormone/LHCGR complex, followed by experimental characterization of relevant fragments in the hinge region. In addition, we examined predictions of a helical exon10-encoded conformation by block-wise polyalanine (helix supporting) mutations. These helix preserving modifications showed no effect on hormone-induced signaling. However, introduction of a structure-disturbing double-proline mutant LHCGR-Q303P/E305P within the exon10-helix has, in contrast to exon10-deletion, no impact on hLH, but only on hCG signaling. This opposite effect on signaling by hLH and hCG can be explained by distinct sites of hormone interaction in the hinge region. In conclusion, our analysis provides details of the differences between hLH- and hCG-induced signaling that are mainly determined in the L2-beta loop of the hormones and in the

  3. INFLUENCING OF FRICTION IN HINGES FORCE SIZE OF BARS

    Directory of Open Access Journals (Sweden)

    BOHOMAZ V. N.

    2016-04-01

    Full Text Available Formulation of the problem. The size of critical force of bar on the traditional method of calculation is determined in supposition of ideal hinge in the place of fixing of bar. There are both a hinge resistance at the turn of bar ends and their moving in the real hinges. Thus, there is the necessity of influencing character determination of these hinge imperfections on the size of critical force. In the existent scientific labours is devoted the alike problems, influencing of friction in the hinges of bar fastening on the size of critical force was not taken into account. At determination of bars stability with no ideality of hinges friction in them it is possible to take into account by the eccentric appendix of loading or appendix of moment. However at such approach it is difficult enough to define the size of attached force or moment. Purpose. To set influencing of friction in the hinge of bar fastening on of his critical force size in sense of Euler, and also build dependences for determination of bar critical force taking into account mechanical descriptions of hinges materials. Conclusion. For the task of determination the size of bar critical force with the joint fastening on ends are got the dependences which take into account mechanical descriptions of material hinge. The received dependences allow to define more exact meaning of critical force for bars. The examples of calculation of whole bar and bar with undercuting in the middle are resulted that values of critical force, certain on a traditional method are overpriced.

  4. An automatic hinge system for leg orthoses

    NARCIS (Netherlands)

    Rietman, J.S.; Goudsmit, J.; Meulemans, D.; Halbertsma, J.P.K.; Geertzen, J.H.B.

    This paper describes a new, automatic hinge system for leg orthoses, which provides knee stability in stance, and allows knee-flexion during swing. Indications for the hinge system are a paresis or paralysis of the quadriceps muscles. Instrumented gait analysis was performed in three patients,

  5. An automatic hinge system for leg orthoses

    NARCIS (Netherlands)

    Rietman, J. S.; Goudsmit, J.; Meulemans, D.; Halbertsma, J. P. K.; Geertzen, J. H. B.

    2004-01-01

    This paper describes a new automatic hinge system for leg orthoses, which provides knee stability in stance, and allows knee-flexion during swing. Indications for the hinge system are a paresis or paralysis of the quadriceps muscles. Instrumented gait analysis was performed in three patients, fitted

  6. Cyclic plastic hinges with degradation effects for frame structures

    DEFF Research Database (Denmark)

    Tidemann, Lasse; Krenk, Steen

    2017-01-01

    A model of cyclic plastic hinges in frame structures including degradation effects for stiffness and strength is developed. The model is formulated via potentials in terms of section forces. It consists of a yield surface, described in a generic format permitting representation of general convex...... shapes including corners, and a set of evolution equations based on an internal energy potential and a plastic flow potential. The form of these potentials is specified by five parameters for each generalized stress-strain component describing yield level, ultimate stress capacity, elastic...... and stiffness parameters. The cyclic plastic hinges are introduced into a six-component equilibrium-based beam element, using additive element and hinge flexibilities. When converted to stiffness format the plastic hinges are incorporated into the element stiffness matrix. The cyclic plastic hinge model...

  7. Experimental investigation of hinged and spring loaded rolling piston compressors pertaining to a turbo rotary engine

    International Nuclear Information System (INIS)

    Okur, Melih; Akmandor, Ibrahim Sinan

    2011-01-01

    Hinged rolling piston compressor of a new thermodynamic cycle Pars engine promises high performance figures such as single stage high compression levels and higher volume flow discharge with competitively low input power and torque. The pumping characteristic of the present engine compressor unit has been increased by the implementation of a spring less vane configuration. The reciprocating vane which is usually operated by spring compression in air conditioning and refrigeration unit has been replaced by a hinge vane mechanism. At high speeds, the conventional spring loaded vane which is forced against the eccentrically moving rotor periphery does disconnect and starts rocking. With the new configuration, this mishap has been eliminated and subsequently resulting compressor pressure leaks have been avoided. Compressor experiments have been carried out at predetermined rotor speeds and compressed volume flow amounts and required shaft powers have been measured and derived accordingly. Experimentally determined pressure-volume relations have been compared with isentropic, isothermal, isochoric compressions as well as isobaric process. It is seen that at lower speeds, hinged vane compression is half way between isentropic and isochoric compressions whereas at high speed the compression process approaches further isochoric compression behavior. The isentropic compression efficiency of the hinged vane compressor is around 85% for pressures reaching 9 atm. - Research highlights: → Volume flow rate of rotary vane compressor unit has been increased by a hinged vane mechanism. → Hinged compressor pressure output is almost twice the performance of a spring loaded compressor. → The slipping and rocking of the spring loaded vane against the rolling piston have been eliminated.

  8. Integrin activation dynamics between the RGD-binding site and the headpiece hinge.

    Science.gov (United States)

    Puklin-Faucher, Eileen; Vogel, Viola

    2009-12-25

    Integrins form mechanical links between the extracellular matrix and the cytoskeleton. Although integrin activation is known to be regulated by an allosteric conformational change, which can be induced from the extracellular or intracellular end of the molecule, little is known regarding the sequence of structural events by which signals propagate between distant sites. Here, we reveal with molecular dynamics simulations of the FnIII(10)-bound alpha(V)beta(3) integrin headpiece how the binding pocket and interdomain betaA/hybrid domain hinge on the distal end of the betaA domain are allosterically linked via a hydrophobic T-junction between the middle of the alpha1 helix and top of the alpha7 helix. The key results of this study are: 1) that this T-junction is induced by ligand binding and hinge opening, and thus displays bidirectionality; 2) that formation of this junction can be accelerated by ligand-mediated force; and 3) how formation of this junction is inhibited by Ca(2+) in place of Mg(2+) at the site adjacent to the metal ion-dependent adhesion site ("ADMIDAS"). Together with recent experimental evidence that integrin complexes can form catch bonds (i.e. become strengthened under force), as well as earlier evidence that Ca(2+) at the ADMIDAS results in lower binding affinity, these simulations provide a common structural model for the dynamic process by which integrins become activated.

  9. Integrin Activation Dynamics between the RGD-binding Site and the Headpiece Hinge*

    Science.gov (United States)

    Puklin-Faucher, Eileen; Vogel, Viola

    2009-01-01

    Integrins form mechanical links between the extracellular matrix and the cytoskeleton. Although integrin activation is known to be regulated by an allosteric conformational change, which can be induced from the extracellular or intracellular end of the molecule, little is known regarding the sequence of structural events by which signals propagate between distant sites. Here, we reveal with molecular dynamics simulations of the FnIII10-bound αVβ3 integrin headpiece how the binding pocket and interdomain βA/hybrid domain hinge on the distal end of the βA domain are allosterically linked via a hydrophobic T-junction between the middle of the α1 helix and top of the α7 helix. The key results of this study are: 1) that this T-junction is induced by ligand binding and hinge opening, and thus displays bidirectionality; 2) that formation of this junction can be accelerated by ligand-mediated force; and 3) how formation of this junction is inhibited by Ca2+ in place of Mg2+ at the site adjacent to the metal ion-dependent adhesion site (“ADMIDAS”). Together with recent experimental evidence that integrin complexes can form catch bonds (i.e. become strengthened under force), as well as earlier evidence that Ca2+ at the ADMIDAS results in lower binding affinity, these simulations provide a common structural model for the dynamic process by which integrins become activated. PMID:19762919

  10. Non-equivalent role of TM2 gating hinges in heteromeric Kir4.1/Kir5.1 potassium channels

    OpenAIRE

    Shang, Lijun; Tucker, Stephen J.

    2007-01-01

    Comparison of the crystal structures of the KcsA and MthK potassium channels suggests that the process of opening a K+ channel involves pivoted bending of the inner pore-lining helices at a highly conserved glycine residue. This bending motion is proposed to splay the transmembrane domains outwards to widen the gate at the ?helix-bundle crossing?. However, in the inwardly rectifying (Kir) potassium channel family, the role of this ?hinge? residue in the second transmembrane domain (TM2) and t...

  11. Deployment Testing of Flexible Composite Hinges in Bi-Material Beams

    Science.gov (United States)

    Sauder, Jonathan F.; Trease, Brian

    2016-01-01

    Composites have excellent properties for strength, thermal stability, and weight. However, they are traditionally highly rigid, and when used in deployable structures require hinges bonded to the composite material, which increases complexity and opportunities for failure. Recent research in composites has found by adding an elastomeric soft matrix, often silicone instead of an epoxy, the composite becomes flexible. This work explores the deployment repeatability of silicone matrix composite hinges which join rigid composite beams. The hinges were found to have sub-millimeter linear deployment repeatability, and sub-degree angular deployment repeatability. Also, an interesting relaxation effect was discovered, as a hinges deployment error would decrease with time.

  12. A Flexible Domain-Domain Hinge Promotes an Induced-fit Dominant Mechanism for the Loading of Guide-DNA into Argonaute Protein in Thermus thermophilus

    KAUST Repository

    Zhu, Lizhe

    2016-02-24

    Argonaute proteins (Ago) are core components of the RNA Induced Silencing Complex (RISC) that load and utilize small guide nucleic acids to silence mRNAs or cleave foreign DNAs. Despite the essential role of Ago in gene regulation and defense against virus, the molecular mechanism of guide-strand loading into Ago remains unclear. We explore such a mechanism in the bacterium Thermus thermophilus Ago (TtAgo), via a computational approach combining molecular dynamics, bias-exchange metadynamics, and protein-DNA docking. We show that apo TtAgo adopts multiple closed states that are unable to accommodate guide-DNA. Conformations able to accommodate the guide are beyond the reach of thermal fluctuations from the closed states. These results suggest an induced-fit dominant mechanism for guide-strand loading in TtAgo, drastically different from the two-step mechanism for human Ago 2 (hAgo2) identified in our previous study. Such a difference between TtAgo and hAgo2 is found to mainly originate from the distinct rigidity of their L1-PAZ hinge. Further comparison among known Ago structures from various species indicates that the L1-PAZ hinge may be flexible in general for prokaryotic Agos but rigid for eukaryotic Agos. © 2016 American Chemical Society.

  13. A Flexible Domain-Domain Hinge Promotes an Induced-fit Dominant Mechanism for the Loading of Guide-DNA into Argonaute Protein in Thermus thermophilus.

    Science.gov (United States)

    Zhu, Lizhe; Jiang, Hanlun; Sheong, Fu Kit; Cui, Xuefeng; Gao, Xin; Wang, Yanli; Huang, Xuhui

    2016-03-17

    Argonaute proteins (Ago) are core components of the RNA Induced Silencing Complex (RISC) that load and utilize small guide nucleic acids to silence mRNAs or cleave foreign DNAs. Despite the essential role of Ago in gene regulation and defense against virus, the molecular mechanism of guide-strand loading into Ago remains unclear. We explore such a mechanism in the bacterium Thermus thermophilus Ago (TtAgo), via a computational approach combining molecular dynamics, bias-exchange metadynamics, and protein-DNA docking. We show that apo TtAgo adopts multiple closed states that are unable to accommodate guide-DNA. Conformations able to accommodate the guide are beyond the reach of thermal fluctuations from the closed states. These results suggest an induced-fit dominant mechanism for guide-strand loading in TtAgo, drastically different from the two-step mechanism for human Ago 2 (hAgo2) identified in our previous study. Such a difference between TtAgo and hAgo2 is found to mainly originate from the distinct rigidity of their L1-PAZ hinge. Further comparison among known Ago structures from various species indicates that the L1-PAZ hinge may be flexible in general for prokaryotic Ago's but rigid for eukaryotic Ago's.

  14. Dry eyes and corneal sensation after laser in situ keratomileusis with femtosecond laser flap creation Effect of hinge position, hinge angle, and flap thickness.

    Science.gov (United States)

    Mian, Shahzad I; Li, Amy Y; Dutta, Satavisha; Musch, David C; Shtein, Roni M

    2009-12-01

    To determine whether corneal sensation and dry-eye signs and symptoms after myopic laser in situ keratomileusis (LASIK) surgery with a femtosecond laser are affected by varying hinge position, hinge angle, or flap thickness. University-based academic practice, Ann Arbor, Michigan, USA. This prospective randomized contralateral-eye study evaluated eyes after bilateral myopic LASIK with a femtosecond laser (IntraLase). Superior and temporal hinge positions, 45-degree and 90-degree hinge angles, and 100 microm and 130 microm corneal flap thicknesses were compared. Postoperative follow-up at 1 week and 1, 3, 6, and 12 months included central Cochet-Bonnet esthesiometry, the Ocular Surface Disease Index questionnaire, a Schirmer test with anesthesia, tear breakup time (TBUT), corneal fluorescein staining, and conjunctival lissamine green staining. The study evaluated 190 consecutive eyes (95 patients). Corneal sensation was reduced at all postoperative visits, with improvement over 12 months (P<.001). There was no difference in corneal sensation between the different hinge positions, angles, or flap thicknesses at any time point. The overall ocular surface disease index score was increased at 1 week, 1 month, and 3 months (P<.0001, P<.0001, and P = .046, respectively). The percentage of patients with a TBUT longer than 10 seconds was significantly lower at 1 week and 1 month (P<.0001). Dry-eye syndrome after myopic LASIK with a femtosecond laser was mild and improved after 3 months. Corneal flap hinge position, hinge angle, and thickness had no effect on corneal sensation or dry-eye syndrome.

  15. Impact of Plastic Hinge Properties on Capacity Curve of Reinforced Concrete Bridges

    Directory of Open Access Journals (Sweden)

    Nasim Shatarat

    2017-01-01

    Full Text Available Pushover analysis is becoming recently the most practical tool for nonlinear analysis of regular and irregular highway bridges. The nonlinear behaviour of structural elements in this type of analysis can be modeled through automated-hinge or user-defined hinge models. The nonlinear properties of the user-defined hinge model for existing highway bridges can be determined in accordance with the recommendations of the Seismic Retrofit Manual by the Federal Highway Administration (FHWA-SRM. Finite element software such as the software SAP2000 offers a simpler and easier approach to determine the nonlinear hinge properties through the automated-hinge model which are determined automatically from the member material and cross section properties. However, the uncertainties in using the automated-hinge model in place of user-defined hinge model have never been addressed, especially for existing and widened bridges. In response to this need, pushover analysis was carried out for four old highway bridges, of which two were widened using the same superstructure but with more attention to seismic detailing requirements. The results of the analyses showed noticeable differences in the capacity curves obtained utilizing the user-defined and automated-hinge models. The study recommends that bridge design manuals clearly ask bridge designers to evaluate the deformation capacities of existing bridges and widened bridges using user-defined hinge model that is determined in accordance with the provisions of the FHWA-SRM.

  16. The role of hinges in primary total knee replacement.

    Science.gov (United States)

    Gehrke, T; Kendoff, D; Haasper, C

    2014-11-01

    The use of hinged implants in primary total knee replacement (TKR) should be restricted to selected indications and mainly for elderly patients. Potential indications for a rotating hinge or pure hinge implant in primary TKR include: collateral ligament insufficiency, severe varus or valgus deformity (>20°) with necessary relevant soft-tissue release, relevant bone loss including insertions of collateral ligaments, gross flexion-extension gap imbalance, ankylosis, or hyperlaxity. Although data reported in the literature are inconsistent, clinical results depend on implant design, proper technical use, and adequate indications. We present our experience with a specific implant type that we have used for over 30 years and which has given our elderly patients good mid-term results. Because revision of implants with long cemented stems can be very challenging, an effort should be made in the future to use shorter stems in modular versions of hinged implants. ©2014 The British Editorial Society of Bone & Joint Surgery.

  17. Incremental-hinge piping analysis methods for inelastic seismic response prediction

    International Nuclear Information System (INIS)

    Jaquay, K.R.; Castle, W.R.; Larson, J.E.

    1989-01-01

    This paper proposes nonlinear seismic response prediction methods for nuclear piping systems based on simplified plastic hinge analyses. The simplified plastic hinge analyses utilize an incremental series of flat response spectrum loadings and replace yielded components with hinge elements when a predefined hinge moment is reached. These hinge moment values, developed by Rodabaugh, result in inelastic energy dissipation of the same magnitude as observed in seismic tests of piping components. Two definitions of design level equivalent loads are employed: one conservatively based on the peaks of the design acceleration response spectra, the other based on inelastic frequencies determined by the method of Krylov and Bogolyuboff recently extended by Lazzeri to piping. Both definitions account for piping system inelastic energy dissipation using Newmark-Hall inelastic response spectrum reduction factors and the displacement ductility results of the incremental-hinge analysis. Two ratchet-fatigue damage models are used: one developed by Rodabaugh that conservatively correlates Markl static fatigue expressions to seismic tests to failure of piping components; the other developed by Severud that uses the ratchet expression of Bree for elbows and Edmunds and Beer for straights, and defines ratchet-fatigue interaction using Coffin's ductility based fatigue equation. Comparisons of predicted behavior versus experimental results are provided for a high-level seismic test of a segment of a representative nuclear plant piping system. (orig.)

  18. Adaptive fiber optics collimator based on flexible hinges.

    Science.gov (United States)

    Zhi, Dong; Ma, Yanxing; Ma, Pengfei; Si, Lei; Wang, Xiaolin; Zhou, Pu

    2014-08-20

    In this manuscript, we present a new design for an adaptive fiber optics collimator (AFOC) based on flexible hinges by using piezoelectric stacks actuators for X-Y displacement. Different from traditional AFOC, the new structure is based on flexible hinges to drive the fiber end cap instead of naked fiber. We fabricated a real AFOC based on flexible hinges, and the end cap's deviation and resonance frequency of the device were measured. Experimental results show that this new AFOC can provide fast control of tip-tilt deviation of the laser beam emitting from the end cap. As a result, the fiber end cap can support much higher power than naked fiber, which makes the new structure ideal for tip-tilt controlling in a high-power fiber laser system.

  19. Analysis of a piping system under seismic load using incremental hinge technique

    International Nuclear Information System (INIS)

    Ravi Kiran, A.; Agrawal, M.K.; Reddy, G.R.; Singh, R.K.; Vaze, K.K.; Ghosh, A.K.; Kushwaha, H.S.; Ramesh Babu, R.

    2008-01-01

    ASME Boiler and Pressure Vessel Code treats piping system as a series of components but not as an overall structural system. Limit analyses and collapse tests at component level are used to establish stress allowables on seismic stresses. The code does not consider the load redistributions and structural redundancy existing in piping systems that prevent system collapse even when one or more individual components loaded beyond their collapse levels. This necessitates a simple analytical method for evaluation of inelastic seismic response at system level. The present paper presents a simplified analytical procedure for predicting inelastic response of a typical piping system subjected to seismic load. The analytical method known as incremental hinge technique is based on plastic system behavior in which the yielded components are replaced with hinge models when a critical hinge moment is reached. It also takes into account the inelastic response spectrum reduction factors and displacement ductility. The analytical method is used to obtain the inelastic response, location of hinge formation and level of base excitation needed for hinge formation. The predicted hinge locations and hinge ordering is compared with the results of a shake table test conducted on the piping system. (author)

  20. Enhanced multimaterial 4D printing with active hinges

    Science.gov (United States)

    Akbari, Saeed; Hosein Sakhaei, Amir; Kowsari, Kavin; Yang, Bill; Serjouei, Ahmad; Yuanfang, Zhang; Ge, Qi

    2018-06-01

    Despite great progress in four-dimensional (4D) printing, i.e. three-dimensional (3D) printing of active (stimuli-responsive) materials, the relatively low actuation force of the 4D printed structures often impedes their engineering applications. In this study, we use multimaterial inkjet 3D printing technology to fabricate shape memory structures, including a morphing wing flap and a deployable structure, which consist of active and flexible hinges joining rigid (non-active) parts. The active hinges, printed from a shape memory polymer (SMP), lock the structure into a second temporary shape during a thermomechanical programming process, while the flexible hinges, printed from an elastomer, effectively increase the actuation force and the load-bearing capacity of the printed structure as reflected in the recovery ratio. A broad range of mechanical properties such as modulus and failure strain can be achieved for both active and flexible hinges by varying the composition of the two base materials, i.e. the SMP and the elastomer, to accommodate large deformation induced during programming step, and enhance the recovery in the actuating step. To find the important design parameters, including local deformation, shape fixity and recovery ratio, we conduct high fidelity finite element simulations, which are able to accurately predict the nonlinear deformation of the printed structures. In addition, a coupled thermal-electrical finite element analysis was performed to model the heat transfer within the active hinges during the localized Joule heating process. The model predictions showed good agreement with the measured temperature data and were used to find the major parameters affecting temperature distribution including the applied voltage and the convection rate.

  1. Seismic response analysis for hinged-leg type port crane

    Energy Technology Data Exchange (ETDEWEB)

    Kashiwazaki, A.; Kanayama, T.; Arai, K. [Ishikawajima-Harima Heavy Industries Co. Ltd., Tokyo (Japan)

    2000-04-01

    Container cranes and unloaders in Kobe Pont were severely damaged during the Southern Hyogo Prefecture Earthquake in 1995. Notably, some of the hinged-leg type of cranes with hinges at the end of sea-or land-side of legs were overturned. These damages were derived from the uplifting of their legs. To explain the uplifting and overturning behavior, we carried out nonlinear analyses and shaking table tests using a 1/8-scale model of the container crane. The results of nonlinear response analyses of hinged-leg type of crane, which are in an agreement with the state of damages in the Southern Hyogo Prefecture Earthquake and the result of shaking table tests, are described. (author)

  2. Alteration of lysine 178 in the hinge region of the Escherichia coli ada protein interferes with activation of ada, but not alkA, transcription.

    OpenAIRE

    Saget, B M; Shevell, D E; Walker, G C

    1995-01-01

    The ada gene of Escherichia coli K-12 encodes the 39-kDa Ada protein, which consists of two domains joined by a hinge region that is sensitive to proteolytic cleavage in vitro. The amino-terminal domain has a DNA methyltransferase activity that repairs the S-diastereoisomer of methylphosphotriesters while the carboxyl-terminal domain has a DNA methyltransferase activity that repairs O6-methylguanine and O4-methylthymine lesions. Transfer of a methyl group to Cys-69 by repair of a methylphosph...

  3. Optimal design of an extrusion process for a hinge bracket

    International Nuclear Information System (INIS)

    Na, Geum Ju; Jang, Myung Geun; Kim, Jong Bong

    2016-01-01

    This study considers process design in forming a hinge bracket. A thin hinge bracket is typically produced by bending a sheet panel or welding a hollow bar into a sheet panel. However, the hinge bracket made by bending or welding does not have sufficient durability in severe operating conditions because of the stress concentration in the bended region or the low corrosion resistance of the welded region. Therefore, this study uses forming to produce the hinge bracket part of a foldable container and to ensure durability in difficult operating conditions. An extrusion process for a T-shaped hinge bracket is studied using finite element analysis. Preliminary analysis shows that a very high forging load is required to form the bracket by forging. Therefore, extrusion is considered as a candidate process. Producing the part through the extrusion process enables many brackets to be made in a single extrusion and through successive cutting of the extruded part, thereby reducing the manufacturing cost. The design focuses on reducing the extrusion load and on ensuring shape accuracy. An initial billet is designed to reduce the extrusion load and to obtain a geometrically accurate part. The extruded part is bent frequently because of uneven material flow. Thus, extrusion die geometries are designed to obtain straight parts.

  4. Optimal design of an extrusion process for a hinge bracket

    Energy Technology Data Exchange (ETDEWEB)

    Na, Geum Ju; Jang, Myung Geun; Kim, Jong Bong [Seoul National University, Seoul (Korea, Republic of)

    2016-05-15

    This study considers process design in forming a hinge bracket. A thin hinge bracket is typically produced by bending a sheet panel or welding a hollow bar into a sheet panel. However, the hinge bracket made by bending or welding does not have sufficient durability in severe operating conditions because of the stress concentration in the bended region or the low corrosion resistance of the welded region. Therefore, this study uses forming to produce the hinge bracket part of a foldable container and to ensure durability in difficult operating conditions. An extrusion process for a T-shaped hinge bracket is studied using finite element analysis. Preliminary analysis shows that a very high forging load is required to form the bracket by forging. Therefore, extrusion is considered as a candidate process. Producing the part through the extrusion process enables many brackets to be made in a single extrusion and through successive cutting of the extruded part, thereby reducing the manufacturing cost. The design focuses on reducing the extrusion load and on ensuring shape accuracy. An initial billet is designed to reduce the extrusion load and to obtain a geometrically accurate part. The extruded part is bent frequently because of uneven material flow. Thus, extrusion die geometries are designed to obtain straight parts.

  5. Magnetic Actuation of Self-Assembled DNA Hinges

    Science.gov (United States)

    Lauback, S.; Mattioli, K.; Armstrong, M.; Miller, C.; Pease, C.; Castro, C.; Sooryakumar, R.

    DNA nanotechnology offers a broad range of applications spanning from the creation of nanoscale devices, motors and nanoparticle templates to the development of precise drug delivery systems. Central to advancing this technology is the ability to actuate or reconfigure structures in real time, which is currently achieved primarily by DNA strand displacement yielding slow actuation times (about 1-10min). Here we exploit superparamagnetic beads to magnetically actuate DNA structures which also provides a system to measure forces associated with molecular interactions. DNA nanodevices are folded using DNA origami, whereby a long single-stranded DNA is folded into a precise compact geometry using hundreds of short oligonucleotides. Our DNA nanodevice is a nanohinge from which rod shaped DNA nanostructures are polymerized into micron-scale filaments forming handles for actuation. By functionalizing one arm of the hinge and the filament ends, the hinge can be attached to a surface while still allowing an arm to rotate and the filaments can be labeled with magnetic beads enabling the hinge to be actuated almost instantaneously by external magnetic fields. These results lay the groundwork to establish real-time manipulation and direct force application of DNA constructs.

  6. A fully redundant power hinge for LANDSAT-D appendages

    Science.gov (United States)

    Mamrol, F. E.; Matteo, D. N.

    1981-01-01

    The configuration and testing of a power driven hinge for deployment of the solar array and antenna boom for the LANDSAT-D spacecraft is discussed. The hinge is fully mechanically and electrically redundant and, thereby, can sustain a single point failure of any one motor (or its power supply), speed reducer, or bearing set without loss of its ability to function. This design utilizes the capability of the stepper motor drive to remove the flexibility of the drive train from the joint stiffness equation when the hinge is loaded against its stop. This feature precludes gapping of the joint under spacecraft maneuver loads even in the absence of a latching feature. Thus, retraction is easily accomplished by motor reversal without the need for a solenoid function to remove the latch.

  7. Creep and cracking of concrete hinges: insight from centric and eccentric compression experiments.

    Science.gov (United States)

    Schlappal, Thomas; Schweigler, Michael; Gmainer, Susanne; Peyerl, Martin; Pichler, Bernhard

    2017-01-01

    Existing design guidelines for concrete hinges consider bending-induced tensile cracking, but the structural behavior is oversimplified to be time-independent. This is the motivation to study creep and bending-induced tensile cracking of initially monolithic concrete hinges systematically. Material tests on plain concrete specimens and structural tests on marginally reinforced concrete hinges are performed. The experiments characterize material and structural creep under centric compression as well as bending-induced tensile cracking and the interaction between creep and cracking of concrete hinges. As for the latter two aims, three nominally identical concrete hinges are subjected to short-term and to longer-term eccentric compression tests. Obtained material and structural creep functions referring to centric compression are found to be very similar. The structural creep activity under eccentric compression is significantly larger because of the interaction between creep and cracking, i.e. bending-induced cracks progressively open and propagate under sustained eccentric loading. As for concrete hinges in frame-like integral bridge construction, it is concluded (i) that realistic simulation of variable loads requires consideration of the here-studied time-dependent behavior and (ii) that permanent compressive normal forces shall be limited by 45% of the ultimate load carrying capacity, in order to avoid damage of concrete hinges under sustained loading.

  8. Control-surface hinge-moment calculations for a high-aspect-ratio supercritical wing

    Science.gov (United States)

    Perry, B., III

    1978-01-01

    The hinge moments, at selected flight conditions, resulting from deflecting two trailing edge control surfaces (one inboard and one midspan) on a high aspect ratio, swept, fuel conservative wing with a supercritical airfoil are estimated. Hinge moment results obtained from procedures which employ a recently developed transonic analysis are given. In this procedure a three dimensional inviscid transonic aerodynamics computer program is combined with a two dimensional turbulent boundary layer program in order to obtain an interacted solution. These results indicate that trends of the estimated hinge moment as a function of deflection angle are similar to those from experimental hinge moment measurements made on wind tunnel models with swept supercritical wings tested at similar values of free stream Mach number and angle of attack.

  9. Operational characterization of CSFH MEMS technology based hinges

    Science.gov (United States)

    Crescenzi, Rocco; Balucani, Marco; Belfiore, Nicola Pio

    2018-05-01

    Progress in MEMS technology continuously stimulates new developments in the mechanical structure of micro systems, such as, for example, the concept of so-called CSFH (conjugate surfaces flexural hinge), which makes it possible, simultaneously, to minimize the internal stresses and to increase motion range and robustness. Such a hinge may be actuated by means of a rotary comb-drive, provided that a proper set of simulations and tests are capable to assess its feasibility. In this paper, a CSFH has been analyzed with both theoretical and finite element (FEM) methods, in order to obtain the relation between voltage and generated torque. The FEM model considers also the fringe effect on the comb drive finger. Electromechanical couple-field analysis is performed by means of both direct and load transfer methods. Experimental tests have been also performed on a CSFH embedded in a MEMS prototype, which has been fabricated starting from a SOI wafer and using D-RIE (deep reactive ion etching). Results showed that CSFH performs better than linear flexure hinges in terms of larger rotations and less stress for given applied voltage.

  10. Evolution of Parallel Spindles Like genes in plants and highlight of unique domain architecture#

    Directory of Open Access Journals (Sweden)

    Consiglio Federica M

    2011-03-01

    Full Text Available Abstract Background Polyploidy has long been recognized as playing an important role in plant evolution. In flowering plants, the major route of polyploidization is suggested to be sexual through gametes with somatic chromosome number (2n. Parallel Spindle1 gene in Arabidopsis thaliana (AtPS1 was recently demonstrated to control spindle orientation in the 2nd division of meiosis and, when mutated, to induce 2n pollen. Interestingly, AtPS1 encodes a protein with a FHA domain and PINc domain putatively involved in RNA decay (i.e. Nonsense Mediated mRNA Decay. In potato, 2n pollen depending on parallel spindles was described long time ago but the responsible gene has never been isolated. The knowledge derived from AtPS1 as well as the availability of genome sequences makes it possible to isolate potato PSLike (PSL and to highlight the evolution of PSL family in plants. Results Our work leading to the first characterization of PSLs in potato showed a greater PSL complexity in this species respect to Arabidopsis thaliana. Indeed, a genomic PSL locus and seven cDNAs affected by alternative splicing have been cloned. In addition, the occurrence of at least two other PSL loci in potato was suggested by the sequence comparison of alternatively spliced transcripts. Phylogenetic analysis on 20 Viridaeplantae showed the wide distribution of PSLs throughout the species and the occurrence of multiple copies only in potato and soybean. The analysis of PSLFHA and PSLPINc domains evidenced that, in terms of secondary structure, a major degree of variability occurred in PINc domain respect to FHA. In terms of specific active sites, both domains showed diversification among plant species that could be related to a functional diversification among PSL genes. In addition, some specific active sites were strongly conserved among plants as supported by sequence alignment and by evidence of negative selection evaluated as difference between non-synonymous and

  11. Prokurör nägi inimliku jõhkruse piiritust / Hinge Brand ; interv. Tiiu Põld

    Index Scriptorium Estoniae

    Brand, Hinge, 1940-2007

    2006-01-01

    Intervjuu ametist lahkuva prokurör Hinge Brandiga. Lisatud: Hinge Brandi CV; Hinge Brandi osavõtul peetud kõmulisemad mõrvaprotsessid. Kommenteerivad Aivar Pilv, Elmar Vaher, Alar Kirs, Eda Murak, Dilaila Nahkur-Tammiksaar

  12. Inelastic seismic response of precast concrete frames with constructed plastic hinges

    Science.gov (United States)

    Sucuoglu, H.

    1995-07-01

    A modified seismic design concept is introduced for precast concrete frames in which beam plastic hinges with reduced yield capacities are constructed away from the precast beam-column connections arranged at the column faces. Plastic hinge location and yield capacity are employed as the basic parameters of an analytical survey in which the inelastic dynamic responses of a conventional precast frame and its modified counterparts are calculated and compared under two earthquake excitations by using a general purpose computer program for dynamic analysis of inelastic frames (left bracket) 1, 2 (right bracket). An optimum design is obtained by providing plastic hinges on precast beams located at one depth away from the beam ends, in which primary (negative) bending moment yield capacities are reduced between one-third and one-quarter of the beam design end moments. With such plastic hinge configurations, precast beam-column connections at the column faces can be designed to remain elastic under strong earthquake excitations.

  13. Numerical investigation of the performance of three hinge designs of bileaflet mechanical heart valves.

    Science.gov (United States)

    Simon, Hélène A; Ge, Liang; Sotiropoulos, Fotis; Yoganathan, Ajit P

    2010-11-01

    Thromboembolic complications (TECs) of bileaflet mechanical heart valves (BMHVs) are believed to be due to the nonphysiologic mechanical stresses imposed on blood elements by the hinge flows. Relating hinge flow features to design features is, therefore, essential to ultimately design BMHVs with lower TEC rates. This study aims at simulating the pulsatile three-dimensional hinge flows of three BMHVs and estimating the TEC potential associated with each hinge design. Hinge geometries are constructed from micro-computed tomography scans of BMHVs. Simulations are conducted using a Cartesian sharp-interface immersed-boundary methodology combined with a second-order accurate fractional-step method. Leaflet motion and flow boundary conditions are extracted from fluid-structure-interaction simulations of BMHV bulk flow. The numerical results are analyzed using a particle-tracking approach coupled with existing blood damage models. The gap width and, more importantly, the shape of the recess and leaflet are found to impact the flow distribution and TEC potential. Smooth, streamlined surfaces appear to be more favorable than sharp corners or sudden shape transitions. The developed framework will enable pragmatic and cost-efficient preclinical evaluation of BMHV prototypes prior to valve manufacturing. Application to a wide range of hinges with varying design parameters will eventually help in determining the optimal hinge design.

  14. Burst protection for reactor pressure vessels using a hinged support bearing

    International Nuclear Information System (INIS)

    Michel, E.; Maritsch, F.

    1976-01-01

    The invention deals with a simplification of the design and manufacture and the way of controlling a hinged support bearing used as burst protection. The pure pressure load of the, e.g., 32 hinged supports distributed along the circumference of the pressure vessel head is achieved in the braced state with little control effort by a pure rotating motion caused pneumatically or hydraulically. The hinged supports are inclined by about 45 0 upwards/outwards in the braced state and with their cap-shaped head and foot are selflocking by pivoted between a supporting structure, firmly connected with the building, and a fishing ring. (TK) [de

  15. Multi-objective optimization of a type of ellipse-parabola shaped superelastic flexure hinge

    Directory of Open Access Journals (Sweden)

    Z. Du

    2016-05-01

    Full Text Available Flexure hinges made of superelastic materials is a promising candidate to enhance the movability of compliant mechanisms. In this paper, we focus on the multi-objective optimization of a type of ellipse-parabola shaped superelastic flexure hinge. The objective is to determine a set of optimal geometric parameters that maximizes the motion range and the relative compliance of the flexure hinge and minimizes the relative rotation error during the deformation as well. Firstly, the paper presents a new type of ellipse-parabola shaped flexure hinge which is constructed by an ellipse arc and a parabola curve. Then, the static responses of superelastic flexure hinges are solved via non-prismatic beam elements derived by the co-rotational approach. Finite element analysis (FEA and experiment tests are performed to verify the modeling method. Finally, a multi-objective optimization is performed and the Pareto frontier is found via the NSGA-II algorithm.

  16. Analysis of intelligent hinged shell structures: deployable deformation and shape memory effect

    Science.gov (United States)

    Shi, Guang-Hui; Yang, Qing-Sheng; He, X. Q.

    2013-12-01

    Shape memory polymers (SMPs) are a class of intelligent materials with the ability to recover their initial shape from a temporarily fixable state when subjected to external stimuli. In this work, the thermo-mechanical behavior of a deployable SMP-based hinged structure is modeled by the finite element method using a 3D constitutive model with shape memory effect. The influences of hinge structure parameters on the nonlinear loading process are investigated. The total shape memory of the processes the hinged structure goes through, including loading at high temperature, decreasing temperature with load carrying, unloading at low temperature and recovering the initial shape with increasing temperature, are illustrated. Numerical results show that the present constitutive theory and the finite element method can effectively predict the complicated thermo-mechanical deformation behavior and shape memory effect of SMP-based hinged shell structures.

  17. Analysis of intelligent hinged shell structures: deployable deformation and shape memory effect

    International Nuclear Information System (INIS)

    Shi, Guang-Hui; Yang, Qing-Sheng; He, X Q

    2013-01-01

    Shape memory polymers (SMPs) are a class of intelligent materials with the ability to recover their initial shape from a temporarily fixable state when subjected to external stimuli. In this work, the thermo-mechanical behavior of a deployable SMP-based hinged structure is modeled by the finite element method using a 3D constitutive model with shape memory effect. The influences of hinge structure parameters on the nonlinear loading process are investigated. The total shape memory of the processes the hinged structure goes through, including loading at high temperature, decreasing temperature with load carrying, unloading at low temperature and recovering the initial shape with increasing temperature, are illustrated. Numerical results show that the present constitutive theory and the finite element method can effectively predict the complicated thermo-mechanical deformation behavior and shape memory effect of SMP-based hinged shell structures. (paper)

  18. Hinge-free topology optimization with embedded translation-invariant differentiable wavelet shrinkage

    DEFF Research Database (Denmark)

    Yoon, G. H.; Kim, Y. Y.; Bendsøe, Martin P.

    2004-01-01

    In topology optimization applications for the design of compliant mechanisms, the formation of hinges is typically encountered. Often such hinges are unphysical artifacts that appear due to the choice of discretization spaces for design and analysis. The objective of this work is to present a new...... two-dimensional compliant mechanism design problems....

  19. Plastic collapse load of crown-hinged steel circular arches : a theoretical method

    NARCIS (Netherlands)

    Spoorenberg, R.C.; Snijder, H.H.; Hoenderkamp, J.C.D.

    2013-01-01

    For construction purposes and to avoid detrimental influences of foundation settlements arches are not always made from a single arch-rib but are built by connecting two curvilinear elements at the crown with a hinge. These arches are also known as crown-hinged arches. This paper presents an

  20. Hinged roof timber

    Energy Technology Data Exchange (ETDEWEB)

    Shestov, P I; Golub, A G; Yefremov, V I

    1980-08-07

    A hinged roof timer is suggested which includes a beam with prong and loop on the end which have openings in the form of ring slits for the distance wedges and round for the pins. In this case the opening of the distance wedge in the ring is arranged in relation to the opening for the pin closer to the end of the beam, and in the prong, in the opposite order. In order to improve the operating quality by guaranteeing active support of the cantilever roof timber without increasing its overall dimensions for the height of the opening for the distance wedge in the prong and the ring, beams are arranged axisymmetrically to the longitudinal axis.

  1. Kinematics analysis on hinges of robot arm gripper for harmful chemical handling

    Science.gov (United States)

    Razali, Zol Bahri; Kader, Mohamed Mydin M. Abdul; Mustafa, Nurul Fahimah; Daud, Mohd Hisam

    2017-09-01

    The development of manufacturing industry is booming the application of industrial robot, and proportional to the use of robot arm. Some of the purpose of robot arm gripper is to sort things and place to the proper place. And some of the things are harmful to human, such as harmful chemical. By using robot arm to do picking and placing, it is expected to replace human tasks, as well as to reduce human from the harmful job. The problem of the robot arm gripper, most likely the problem of hinge, thus the analysis on the hinges of robot arm gripper to prevent claw is essential. By using robot arm, instead of human, is labored to do the harmful tasks and unexpected accident happen, costs and expenses in handling injured employee due to the harmful chemicals can be minimized. Thus the objective of this project is to make a kinematics analysis on the hinges of the robot arm gripper. Suitable material such as steel structure has also been selected for the construction of this hinges. This material has properties associated with compressive strength, fire resistance, corrosion and has a shape that is easy to move. Solid Works and ANSYS software is used to create animated movement on the design model and to detect deficiencies in the hinges. Detail methodology is described in this paper.

  2. Engineering a disulfide bond in the lid hinge region of Rhizopus chinensis lipase: increased thermostability and altered acyl chain length specificity.

    Directory of Open Access Journals (Sweden)

    Xiao-Wei Yu

    Full Text Available The key to enzyme function is the maintenance of an appropriate balance between molecular stability and structural flexibility. The lid domain which is very important for "interfacial activation" is the most flexible part in the lipase structure. In this work, rational design was applied to explore the relationship between lid rigidity and lipase activity by introducing a disulfide bond in the hinge region of the lid, in the hope of improving the thermostability of R. chinensis lipase through stabilization of the lid domain without interfering with its catalytic performance. A disulfide bridge between F95C and F214C was introduced into the lipase from R. chinensis in the hinge region of the lid according to the prediction of the "Disulfide by Design" algorithm. The disulfide variant showed substantially improved thermostability with an eleven-fold increase in the t(1/2 value at 60°C and a 7°C increase of T(m compared with the parent enzyme, probably contributed by the stabilization of the geometric structure of the lid region. The additional disulfide bond did not interfere with the catalytic rate (k(cat and the catalytic efficiency towards the short-chain fatty acid substrate, however, the catalytic efficiency of the disulfide variant towards pNPP decreased by 1.5-fold probably due to the block of the hydrophobic substrate channel by the disulfide bond. Furthermore, in the synthesis of fatty acid methyl esters, the maximum conversion rate by RCLCYS reached 95% which was 9% higher than that by RCL. This is the first report on improving the thermostability of the lipase from R. chinensis by introduction of a disulfide bond in the lid hinge region without compromising the catalytic rate.

  3. Database of ligand-induced domain movements in enzymes

    Directory of Open Access Journals (Sweden)

    Hayward Steven

    2009-03-01

    Full Text Available Abstract Background Conformational change induced by the binding of a substrate or coenzyme is a poorly understood stage in the process of enzyme catalysed reactions. For enzymes that exhibit a domain movement, the conformational change can be clearly characterized and therefore the opportunity exists to gain an understanding of the mechanisms involved. The development of the non-redundant database of protein domain movements contains examples of ligand-induced domain movements in enzymes, but this valuable data has remained unexploited. Description The domain movements in the non-redundant database of protein domain movements are those found by applying the DynDom program to pairs of crystallographic structures contained in Protein Data Bank files. For each pair of structures cross-checking ligands in their Protein Data Bank files with the KEGG-LIGAND database and using methods that search for ligands that contact the enzyme in one conformation but not the other, the non-redundant database of protein domain movements was refined down to a set of 203 enzymes where a domain movement is apparently triggered by the binding of a functional ligand. For these cases, ligand binding information, including hydrogen bonds and salt-bridges between the ligand and specific residues on the enzyme is presented in the context of dynamical information such as the regions that form the dynamic domains, the hinge bending residues, and the hinge axes. Conclusion The presentation at a single website of data on interactions between a ligand and specific residues on the enzyme alongside data on the movement that these interactions induce, should lead to new insights into the mechanisms of these enzymes in particular, and help in trying to understand the general process of ligand-induced domain closure in enzymes. The website can be found at: http://www.cmp.uea.ac.uk/dyndom/enzymeList.do

  4. Effects of thermo-mechanical behavior and hinge geometry on folding response of shape memory polymer sheets

    Science.gov (United States)

    Mailen, Russell W.; Dickey, Michael D.; Genzer, Jan; Zikry, Mohammed

    2017-11-01

    Shape memory polymer (SMP) sheets patterned with black ink hinges change shape in response to external stimuli, such as absorbed thermal energy from an infrared (IR) light. The geometry of these hinges, including size, orientation, and location, and the applied thermal loads significantly influence the final folded shape of the sheet, but these variables have not been fully investigated. We perform a systematic study on SMP sheets to fundamentally understand the effects of single and double hinge geometries, hinge orientation and spacing, initial temperature, heat flux intensity, and pattern width on the folding behavior. We have developed thermo-viscoelastic finite element models to characterize and quantify the stresses, strains, and temperatures as they relate to SMP shape changes. Our predictions indicate that hinge orientation can be used to reduce the total bending angle, which is the angle traversed by the folding face of the sheet. Two parallel hinges increase the total bending angle, and heat conduction between the hinges affects the transient folding response. IR intensity and initial temperatures can also influence the transient folding behavior. These results can provide guidelines to optimize the transient folding response and the three-dimensional folded structure obtained from self-folding polymer origami sheets that can be applied for myriad applications.

  5. Solar array deployment analysis considering path-dependent behavior of a tape spring hinge

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kyung Won; Park, Young Jin [KAIST, Daejeon (Korea, Republic of)

    2015-05-15

    Solar array deployment analysis is conducted considering the path-dependent nonlinear behavior of tape spring hinge. Such hinges offer many advantages over rigid hinges; they are self-deployable, self-locking, lightweight, and simple. However, they show strongly nonlinear behavior with respect to rotation angle, making deployment analysis difficult. To accurately consider the characteristics of tape spring hinges for deployment analysis, a path-dependent path identification (PI) method for tracing the previous path of the moment is introduced. To analyze the deployment motion, the governing equation for solar array deployment is derived within the framework of Kane's dynamic equation for three deployable solar panels. The numerical solution is compared with the Recurdyn's multi-body dynamics analysis solution using experimentally measured moment-rotation profiles. Solar array deployment analysis is conducted by considering and not considering the path-dependent PI method. This simulation example shows that the proposed path-dependent PI method is very effective for accurately predicting the deployment motion.

  6. The effect of klapskate hinge position on push-off performance: a simulation study

    NARCIS (Netherlands)

    Houdijk, J.H.P.; Bobbert, M.F.; de Koning, J.J.; de Groot, G.

    2003-01-01

    Purpose: The introduction of the klapskate in speed skating confronts skaters with the question of how to adjust the position of the hinge in order to maximize performance. The purpose of this study was to reveal the constraint that klapskate hinge position imposes on push-off performance in speed

  7. An optimization approach for black-and-white and hinge-removal topology designs

    Energy Technology Data Exchange (ETDEWEB)

    Fu, Yongqing; Zhang, Xianmin [South China University of Technology, Guangzhou (China)

    2014-02-15

    An optimization approach for black-and-white and hinge-removal topology designs is studied. To achieve this motive, an optimal topology allowing grey boundaries is found firstly. When a suitable design has been obtained, this solution is then used as a starting point for the follow-up optimization with the goal to free unfavorable intermediate elements. For this purpose, an updated optimality criterion in which a threshold factor is introduced to gradually suppress elements with low density is proposed. The typical optimality method and new technique proposed are applied to the design procedure sequentially. Besides, to circumvent the one-point hinge connection problem producing in the process of freeing intermediate elements, a hinge-removal strategy is also proposed. During the optimization, the binary constraints on design variables are relaxed based on the scheme of solid isotropic material with penalization. Meanwhile, the mesh independency filter is employed to ensure the existence of a solution and remove well-known checkerboards. In this way, a solution that has few intermediate elements and is free of one-point hinge connections is obtained. Finally, different numerical examples including the compliance minimization, compliant mechanisms and vibration problems demonstrate the validity of the proposed approach.

  8. Evidence on How a Conserved Glycine in the Hinge Region of HapR Regulates Its DNA Binding Ability: LESSONS FROM A NATURAL VARIANT.

    Energy Technology Data Exchange (ETDEWEB)

    M Dongre; N Singh; C Dureja; N Peddada; A Solanki; F Ashish; S Raychaudhuri

    2011-12-31

    HapR has been recognized as a quorum-sensing master regulator in Vibrio cholerae. Because it controls a plethora of disparate cellular events, the absence of a functional HapR affects the physiology of V. cholerae to a great extent. In the current study, we pursued an understanding of an observation of a natural protease-deficient non-O1, non-O139 variant V. cholerae strain V2. Intriguingly, a nonfunctional HapR (henceforth designated as HapRV2) harboring a substitution of glycine to aspartate at position 39 of the N-terminal hinge region has been identified. An in vitro gel shift assay clearly suggested the inability of HapRV2 to interact with various cognate promoters. Reinstatement of glycine at position 39 restores DNA binding ability of HapRV2 (HapRV2G), thereby rescuing the protease-negative phenotype of this strain. The elution profile of HapRV2 and HapRV2G proteins in size-exclusion chromatography and their circular dichroism spectra did not reflect any significant differences to explain the functional discrepancies between the two proteins. To gain insight into the structure-function relationship of these two proteins, we acquired small/wide angle x-ray scattering data from samples of the native and G39D mutant. Although Guinier analysis and indirect Fourier transformation of scattering indicated only a slight difference in the shape parameters, structure reconstruction using dummy amino acids concluded that although HapR adopts a 'Y' shape similar to its crystal structure, the G39D mutation in hinge drastically altered the DNA binding domains by bringing them in close proximity. This altered spatial orientation of the helix-turn-helix domains in this natural variant provides the first structural evidence on the functional role of the hinge region in quorum sensing-related DNA-binding regulatory proteins of Vibrio spp.

  9. Substrate Binding Induces Domain Movements in Orotidine 5'-Monophosphate Decarboxylase

    DEFF Research Database (Denmark)

    Harris, Pernille Hanne; Poulsen, Jens-Christian Navarro; Jensen, Kaj Frank

    2002-01-01

    ); here we present the 2.5 Å structure of the uncomplexed apo enzyme, determined from twinned crystals. A structural analysis and comparison of the two structures of the E. coli enzyme show that binding of the inhibitor is accompanied by significant domain movements of approximately 12° around a hinge...

  10. A hinged-pad test structure for sliding friction measurement in micromachining

    Energy Technology Data Exchange (ETDEWEB)

    Boer, M.P. de; Redmond, J.M.; Michalske, T.A.

    1998-08-01

    The authors describe the design, modeling, fabrication and initial testing of a new test structure for friction measurement in MEMS. The device consists of a cantilevered forked beam and a friction pad attached via a hinge. Compared to previous test structures, the proposed structure can measure friction over much larger pressure ranges, yet occupies one hundred times less area. The placement of the hinge is crucial to obtaining a well-known and constant pressure distribution in the device. Static deflections on the device were measured and modeled numerically, Preliminary results indicate that friction pad slip is sensitive to friction pad normal force.

  11. The use of modal derivatives in determining stroke-dependent frequencies of large stroke flexure hinges

    NARCIS (Netherlands)

    van den Belt, Mieke; Schilder, Jurnan; Valasek, Michael; Sika, Zbynek; Vampola, Tomas

    2017-01-01

    Nowadays, a lot of use is made of large stroke flexure hinges in precision engineering. However, these large stroke flexure hinges typically lose stiffness in supporting direction during deflection. The lowest natural frequency is a commonly used measure for this property. Therefore, in shape and

  12. The effects of klapskate hinge position on push-off performance: a simulation study.

    Science.gov (United States)

    Houdijk, Han; Bobbert, Maarten F; De Koning, Jos J; De Groot, Gert

    2003-12-01

    The introduction of the klapskate in speed skating confronts skaters with the question of how to adjust the position of the hinge in order to maximize performance. The purpose of this study was to reveal the constraint that klapskate hinge position imposes on push-off performance in speed skating. For this purpose, a model of the musculoskeletal system was designed to simulate a simplified, two-dimensional skating push off. To capture the essence of a skating push off, this model performed a one-leg vertical jump, from a frictionless surface, while keeping its trunk horizontally. In this model, klapskate hinge position was varied by varying the length of the foot segment between 115 and 300 mm. With each foot length, an optimal control solution was found that resulted in the maximal amount of vertical kinetic and potential energy of the body's center of mass at take off (Weff). Foot length was shown to considerably affect push-off performance. Maximal Weff was obtained with a foot length of 185 mm and decreased by approximately 25% at either foot length of 115 mm and 300 mm. The reason for this decrease was that foot length affected the onset and control of foot rotation. This resulted in a distortion of the pattern of leg segment rotations and affected muscle work (Wmus) and the efficacy ratio (Weff/Wmus) of the entire leg system. Despite its simplicity, the model very well described and explained the effects of klapskate hinge position on push off performance that have been observed in speed-skating experiments. The simplicity of the model, however, does not allow quantitative analyses of optimal klapskate hinge position for speed-skating practice.

  13. Seismic performance of a grout-repaired construction defect in a column plastic hinge

    International Nuclear Information System (INIS)

    Budek, A.

    2006-01-01

    A column built to test the use of high-strength transverse reinforcement in seismically-loaded shear-critical columns was found to have a construction defect. The column was built to be loaded in double bending and as such was expected to develop two plastic hinges, one at each end of column. In the plastic hinge region at the column top, a void was formed because the concrete could not pass through the load stub's reinforcing steel cage. This void was repaired using nonshrink grout placed in a fluid state. The column was tested after repair and performed satisfactorily. The grouted repair was able to support large plastic rotations and allowed the column to reach a high level of ductility. The only effects of the repair were slightly reduced concrete dilation and stiffness in the repaired hinge. (author)

  14. Velocity measurements and flow patterns within the hinge region of a Medtronic Parallel bileaflet mechanical valve with clear housing.

    Science.gov (United States)

    Ellis, J T; Healy, T M; Fontaine, A A; Saxena, R; Yoganathan, A P

    1996-11-01

    During recent clinical trials the Medtronic Parallel bileaflet mechanical heart valve was found to have an unacceptable number of valves with thrombus formation when implanted in the mitral position. Thrombi were observed in the hinge region and also in the upstream portion of the valve housing in the vicinity of the hinge. It was hypothesized that the flow conditions inside the hinge may have contributed to the thrombus formation. In order to investigate the flow structures within the hinge, laser Doppler anemometry (LDA) measurements were conducted in both steady and pulsatile flow at approximately 70 predetermined sites within the hinge region of a 27 mm Medtronic Parallel mitral valve with transparent housing. The pulsatile flow velocity measurements were animated in time using a graphical software package to visualize the hinge flow field throughout the cardiac cycle. The LDA measurements revealed that mean forward flow velocities through the hinge region were on the order of 0.10-0.20 m/s. In the inflow channel, a large vortical structure was present during diastole. Upon valve closure, peak reverse velocity reached 3 m/s close to the housing wall in the inflow channel. This area also experienced high turbulent shear stresses (> 6000 dynes/cm2) during the leakage flow phase. A disturbed, vortical flow was again present in the inflow channel after valve closure, while slightly above the leaflet peg and relief the flow was essentially stagnant. The high turbulent stresses near the top of the inflow channel, combined with a persistent vortex, implicate the inflow channel of the hinge as a likely region of thrombus formation. This experimental investigation revealed zones of flow stagnation in the inflow region of the hinge throughout the cardiac cycle and elevated turbulent shear stress levels in the inflow region during the leakage flow phase. These fluid mechanic phenomena are most likely a direct result of the complex geometry of the hinge of this valve

  15. Flow over a cylinder with a hinged-splitter plate

    Science.gov (United States)

    Shukla, S.; Govardhan, R. N.; Arakeri, J. H.

    2009-05-01

    Previous work on rigid splitter plates in the wake of a bluff body has shown that the primary vortex shedding can be suppressed for sufficiently long splitter plates. In the present work, we study the problem of a hinged-splitter plate in the wake of a circular cylinder. The splitter plate can rotate about the hinge at the base of the cylinder due to the unsteady fluid forces acting on it, and hence the communication between the two sides of the wake is not totally disrupted as in the rigid splitter plate case. In our study, we investigate this problem in the limit where the stiffness and internal damping associated with the hinge are negligible, and the mass ratio of the splitter plate is small. The experiments show that the splitter plate oscillations increase with Reynolds numbers at low values of Re, and are found to reach a saturation amplitude level at higher Re, Re>4000. This type of saturation amplitude level that appears to continue indefinitely with Re, appears to be related to the fact that there is no structural restoring force, and has been observed previously for transversely oscillating cylinders with no restoring force. In the present case, the saturation tip amplitude level can be up to 0.45D, where D is the cylinder diameter. For this hinged-rigid splitter plate case, it is found that the splitter plate length to cylinder diameter ratio (L/D) is crucial in determining the character and magnitude of the oscillations. For small splitter plate lengths (L/D⩽3.0), the oscillations appear to be nearly periodic with tip amplitudes of about 0.45D nearly independent of L/D. The nondimensional oscillation frequencies (fD/U) on the other hand are found to continuously vary with L/D from fD/U≈0.2 at L/D=1 to fD/U≈0.1 at L/D=3. As the splitter plate length is further increased beyond L/D⩾4.0, the character of the splitter plate oscillations suddenly changes. The oscillations become aperiodic with much smaller amplitudes. In this long splitter plate

  16. The effect of klapskate hinge position on push-off performance: a simulation study

    OpenAIRE

    Houdijk, J.H.P.; Bobbert, M.F.; de Koning, J.J.; de Groot, G.

    2003-01-01

    Purpose: The introduction of the klapskate in speed skating confronts skaters with the question of how to adjust the position of the hinge in order to maximize performance. The purpose of this study was to reveal the constraint that klapskate hinge position imposes on push-off performance in speed skating. Method: For this purpose, a model of the musculoskeletal system was designed to simulate a simplified, two-dimensional skating push off. To capture the essence of a skating push off, this m...

  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. Influence of hinge point on flexible flap aerodynamic performance

    International Nuclear Information System (INIS)

    Zhao, H Y; Ye, Z; Wu, P; Li, C

    2013-01-01

    Large scale wind turbines lead to increasing blade lengths and weights, which presents new challenges for blade design. This paper selects NREL S809 airfoil, uses the parameterized technology to realize the flexible trailing edge deformation, researches the static aerodynamic characteristics of wind turbine blade airfoil with flexible deformation, and the dynamic aerodynamic characteristics in the process of continuous deformation, analyses the influence of hinge point position on flexible flap aerodynamic performance, in order to further realize the flexible wind turbine blade design and provides some references for the active control scheme. The results show that compared with the original airfoil, proper trailing edge deformation can improve the lift coefficient, reduce the drag coefficient, and thereby more efficiently realize flow field active control. With hinge point moving forward, total aerodynamic performance of flexible flap improves. Positive swing angle can push the transition point backward, thus postpones the occurrence of the transition phenomenon

  19. Comparison of platelet activation through hinge vs bulk flow in mechanical heart valves

    Science.gov (United States)

    Hedayat, Mohammadali; Borazjani, Iman

    2017-11-01

    Bileaflet mechanical heart valves increase the risk of thrombus formation in patients which is believed to be initiated by platelet activation. Platelets can be activated by the elevated shear stresses in the bulk flow during the systole phase or the flow through the hinge during the diastole. However, the importance of platelet activation by the bulk flow vs the hinge in MHVs has yet to be studied. Here, we investigate the contribution of each of the above mechanisms to the activation of platelets in MHs by performing simulation of the flow through a 25mm St. Jude Medical valve placed in a straight aorta. Two different gap sizes (250 and 150 micrometer) are used in this study. The simulations are done using a sharp interface curvilinear immersed boundary method along with a strong-coupling algorithm for FSI solver on overset grids. The platelet activation through the hinge for different gap sizes is compared to the activation in the bulk flow using two platelet activation models to ensure the consistency of the results. Our results for all gap sizes using different activation models show that the integration of platelet activation caused by the bulk flow is several times higher in comparison to the activation through the hinge. This work is supported by the American Heart Association Grant 13SDG17220022, and the computational resources were partly provided by Center for Computational Research (CCR) at University at Buffalo.

  20. DETERMINING THE THERMAL RESISTANCE OF A VENTILATED HINGED FACADE SYSTEM LAYER

    Directory of Open Access Journals (Sweden)

    Gagarin Vladimir Gennad'evich

    2015-03-01

    Full Text Available Enveloping structures with hinged façade systems are nowadays widely used for moisture control of enveloping structures, prevention of overheating of the structures by insolation, saving the constructions from atmospheric moisture and also for correspondence with the raised requirements to thermal protection of the enveloping structures, aimed also at reducing energy consumption. In the winter conditions the influence of air layer on the thermal insulation parameters is usually neglected. In the article the thermal resistance of an air gap and is considered and its effect in the calculation of the heat resistance of a building envelope with hinged facade system is analyzed in the conditions of cold weather. The thermal resistance of the air layer determines how the heat losses decrease.

  1. The epigenetic regulator Smchd1 contains a functional GHKL-type ATPase domain.

    Science.gov (United States)

    Chen, Kelan; Dobson, Renwick C J; Lucet, Isabelle S; Young, Samuel N; Pearce, F Grant; Blewitt, Marnie E; Murphy, James M

    2016-06-15

    Structural maintenance of chromosomes flexible hinge domain containing 1 (Smchd1) is an epigenetic regulator that plays critical roles in gene regulation during development. Mutations in SMCHD1 were recently implicated in the pathogenesis of facioscapulohumeral muscular dystrophy (FSHD), although the mechanistic basis remains of outstanding interest. We have previously shown that Smchd1 associates with chromatin via its homodimeric C-terminal hinge domain, yet little is known about the function of the putative GHKL (gyrase, Hsp90, histidine kinase, MutL)-type ATPase domain at its N-terminus. To formally assess the structure and function of Smchd1's ATPase domain, we have generated recombinant proteins encompassing the predicted ATPase domain and the adjacent region. Here, we show that the Smchd1 N-terminal region exists as a monomer and adopts a conformation resembling that of monomeric full-length heat shock protein 90 (Hsp90) protein in solution, even though the two proteins share only ∼8% overall sequence identity. Despite being monomeric, the N-terminal region of Smchd1 exhibits ATPase activity, which can be antagonized by the reaction product, ADP, or the Hsp90 inhibitor, radicicol, at a nanomolar concentration. Interestingly, introduction of an analogous mutation to that identified in SMCHD1 of an FSHD patient compromised protein stability, suggesting a possible molecular basis for loss of protein function and pathogenesis. Together, these results reveal important structure-function characteristics of Smchd1 that may underpin its mechanistic action at the chromatin level. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

  2. Reconstruction of palatal defect using mucoperiosteal hinge flap and pushback palatoplasty.

    Science.gov (United States)

    Lee, S I; Lee, H S; Hwang, K

    2001-11-01

    This article describes a simple, new surgical technique to provide a complete two-layer closure of palatal defect resulting from a surgical complication of trans palatal resection of skull base chordoma. The nasal layer was reconstructed with triangular shape oral mucoperiosteal turn over hinge flap based on anterior margin of palatal defect and rectangular shaped lateral nasal mucosal hinge flaps. The oral layer was reconstructed with conventional pushback V-Y advancement 2-flaps palatoplasty. Each layer of the flaps were secured with two key mattress suture for flap coaptation. This technique has some advantages: simple, short operation time, one-stage procedure, no need of osteotomy. It can close small- to medium-sized palatal defect of palate or wide cleft palate and can prevent common complication of oronasal fistula, which could be caused by tension.

  3. A stepwise approach for the management of capsular contraction syndrome in hinge-based accommodative intraocular lenses.

    Science.gov (United States)

    Page, Timothy P; Whitman, Jeffrey

    2016-01-01

    The aims of this study are to define the various stages of capsular contraction syndrome (CCS) and its effect on refractive error with hinge-based accommodating intraocular lenses (IOLs) and to describe a systematic approach for the management of the different stages of CCS. Hinge-based accommodative IOLs function via flexible hinges that vault the optic forward during accommodation. However, it is the flexibility of the IOL that makes it prone to deformation in the event of CCS. The signs of CCS are identified and described as posterior capsular striae, fibrotic bands across the anterior or posterior capsule, and capsule opacification. Various degrees of CCS may affect hinge-based accommodating IOLs in a spectrum from subtle changes in IOL appearance to significant increases in refractive error and loss of uncorrected visual acuity. The signs of CCS and its effect on IOL position and the resulting changes in refractive error are matched to appropriate treatment plans. A surgeon can avoid CCS and manage the condition if familiar with the early signs of CCS. If CCS is identified, yttrium-aluminum-garnet laser capsulotomy should be considered. If moderate CCS occurs, it may be effectively treated with insertion of a capsular tension ring. If CCS is allowed to progress to advanced stages, an IOL exchange may be necessary. Surgeons should be familiar with the stages of CCS and subsequent interventions. The steps outlined in this article help to guide surgeons in the prevention and management of CCS with hinge-based accommodative IOLs in order to provide improved refractive outcomes for patients.

  4. Thermoelectric generator with hinged assembly for fins

    International Nuclear Information System (INIS)

    Purdy, D.L.; Shapiro, Z.M.; Hursen, T.F.; Maurer, G.W.

    1976-01-01

    A cylindrical casing has a central shielded capsule of radioisotope fuel. A plurality of thermonuclear modules are axially arranged with their hot junctions resiliently pressed toward the shield and with their cold junctions adjacent a transition member having fins radiating heat to the environment. For each module, the assembly of transition member and fins is hinged to the casing for swinging to permit access to and removal of such module. A ceramic plate having gold layers on opposite faces prevents diffusion bonding of the hot junction to the shield

  5. Functionalisation of the hinge region in receptor molecules for explosive detection

    DEFF Research Database (Denmark)

    Krebs, Frederik C

    2003-01-01

    The functionalisation of the hinge region in a molecular tweezer molecule showing a strong binding to explosives is presented. Two versatile functional groups are introduced, a carboxylic acid and a bromine atom. (C) 2003 Elsevier Ltd. All rights reserved....

  6. How Hinge Positioning in Cross-Country Ski Bindings Affect Exercise Efficiency, Cycle Characteristics and Muscle Coordination during Submaximal Roller Skiing.

    Directory of Open Access Journals (Sweden)

    Conor M Bolger

    Full Text Available The purposes of the current study were to 1 test if the hinge position in the binding of skating skis has an effect on gross efficiency or cycle characteristics and 2 investigate whether hinge positioning affects synergistic components of the muscle activation in six lower leg muscles. Eleven male skiers performed three 4-min sessions at moderate intensity while cross-country ski-skating and using a klapskate binding. Three different positions were tested for the binding's hinge, ranging from the front of the first distal phalange to the metatarsal-phalangeal joint. Gross efficiency and cycle characteristics were determined, and the electromyographic (EMG signals of six lower limb muscles were collected. EMG signals were wavelet transformed, normalized, joined into a multi-dimensional vector, and submitted to a principle component analysis (PCA. Our results did not reveal any changes to gross efficiency or cycle characteristics when altering the hinge position. However, our EMG analysis found small but significant effects of hinge positioning on muscle coordinative patterns (P < 0.05. The changed patterns in muscle activation are in alignment with previously described mechanisms that explain the effects of hinge positioning in speed-skating klapskates. Finally, the within-subject results of the EMG analysis suggested that in addition to the between-subject effects, further forms of muscle coordination patterns appear to be employed by some, but not all participants.

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

    International Nuclear Information System (INIS)

    Martinez, Elisabeth D.; Pattabiraman, Nagarajan; Danielsen, Mark

    2005-01-01

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

  8. A stepwise approach for the management of capsular contraction syndrome in hinge-based accommodative intraocular lenses

    Directory of Open Access Journals (Sweden)

    Page TP

    2016-06-01

    Full Text Available Timothy P Page,1 Jeffrey Whitman2 1Department of Ophthalmology, Oakland University William Beaumont School of Medicine, Royal Oak, MI, 2Key-Whitman Eye Center, Dallas, TX, USA Purpose: The aims of this study are to define the various stages of capsular contraction syndrome (CCS and its effect on refractive error with hinge-based accommodating intraocular lenses (IOLs and to describe a systematic approach for the management of the different stages of CCS. Methods: Hinge-based accommodative IOLs function via flexible hinges that vault the optic forward during accommodation. However, it is the flexibility of the IOL that makes it prone to deformation in the event of CCS. The signs of CCS are identified and described as posterior capsular striae, fibrotic bands across the anterior or posterior capsule, and capsule opacification. Various degrees of CCS may affect hinge-based accommodating IOLs in a spectrum from subtle changes in IOL appearance to significant increases in refractive error and loss of uncorrected visual acuity. The signs of CCS and its effect on IOL position and the resulting changes in refractive error are matched to appropriate treatment plans. Results: A surgeon can avoid CCS and manage the condition if familiar with the early signs of CCS. If CCS is identified, yttrium–aluminum–garnet laser capsulotomy should be considered. If moderate CCS occurs, it may be effectively treated with insertion of a capsular tension ring. If CCS is allowed to progress to advanced stages, an IOL exchange may be necessary. Conclusion: Surgeons should be familiar with the stages of CCS and subsequent interventions. The steps outlined in this article help to guide surgeons in the prevention and management of CCS with hinge-based accommodative IOLs in order to provide improved refractive outcomes for patients. Keywords: z-syndrome, pseudophakic tilt, IOL subluxation, CTR, capsular tension ring, capsular fibrosis

  9. Modeling and design of a two-axis elliptical notch flexure hinge

    Science.gov (United States)

    Wu, Jianwei; Zhang, Yin; Lu, Yunfeng; Wen, Zhongpu; Bin, Deer; Tan, Jiubin

    2018-04-01

    As an important part of the joule balance system, the two-axis elliptical notch flexure hinge (TENFH) which typically consists of two single-axis elliptical notch flexure hinges was studied. First, a 6 degrees of freedom (6-DOF) compliance model was established based on the coordinate transformation method. In addition, the maximum stress of the TENFH was derived. The compliance and maximum stress model was verified using finite element analysis simulation. To decouple the attitude of the suspended coil system and reduce the offset between the centroid of the suspended coil mechanism and the mass comparator in the joule balance system, a new mechanical structure of TENFH was designed based on the compliance model and stress model proposed in this paper. The maximum rotation range is up to 10°, and the axial load is more than 5 kg, which meets the requirements of the system. The compliance model was also verified by deformation experimentation with the designed TENFH.

  10. Structure of the EMMPRIN N-terminal domain 1: Dimerization via [beta]-strand swapping

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Jinquan; Teplyakov, Alexey; Obmolova, Galina; Malia, Thomas; Wu, Sheng-Jiun; Beil, Eric; Baker, Audrey; Swencki-Underwood, Bethany; Zhao, Yonghong; Sprenkle, Justin; Dixon, Ken; Sweet, Raymond; Gilliland, Gary L.; (Centocor)

    2010-09-27

    Extracellular matrix metalloproteinase inducer (EMMPRIN), also known as Hab18G, CD147, Basigin, M6, and neurothelin, is a membrane glycoprotein expressed on the surface of various cell types and many cancer cells. EMMPRIN stimulates adjacent fibroblasts and tumor cells to produce matrix metalloproteinases and plays an important role in tumor invasion and metastasis, angiogenesis, spermatogensis and fertilization, cell-cell adhesion and communication, and other biological processes (reviewed in Ref. 1 and references therein). It was demonstrated that the EMMPRIN extracellular domain (ECD), which structurally belongs to the IgG superfamily, can form homo-oligomers in a cis dependent manner and the N-terminal domain 1 (residues 22-101) was necessary and sufficient to mediate this interaction. The crystal structure of the ECD of recombinant human EMMPRIN (Hab18G/CD147) expressed in E. coli was reported at 2.8 {angstrom} resolution (Yu et al. 2008). The construct consists of residues 22-205 of the mature protein and has both an N-terminal IgC2 domain (ND1, residues 22-101) and a C-terminal IgC2 domain (ND2, residues 107-205). The two domains are joined by a five amino acid residue linker that constitutes a flexible hinge between the two domains. The crystal form has four copies of the molecule in the asymmetric unit, each of which has a different inter-domain angle that varies from 121{sup o} to 144{sup o}. The two domains each have a conserved disulfide bridge and both are comprised of two {beta}-sheets formed by strands EBA and GFCC, and DEBA and AGFCC for ND1 and ND2, respectively. Based on the crystal packing in this structure, the authors proposed that lateral packing between the two IgG domains of EMMPRIN ECD represents a potential mechanism for cell adhesion. Here we report the 2.0-{angstrom} crystal structure of the N-terminal domain of EMMPRIN ECD (ND1) expressed in mammalian cells. The overall structure of the domain is very similar to that in the full length

  11. Hinged and sectional complete dentures for restricted mouth opening: A case report and review

    Directory of Open Access Journals (Sweden)

    Aditi Sharma

    2013-01-01

    Full Text Available Restricted mouth opening is a definite prosthodontic hindrance to carry out treatment successfully. Restricted mouth opening can be due to many reasons such as microstomia, oral submucous fibrosis, some genetic disorder, and as a result of some surgical treatment. In the past, various techniques for prosthetic rehabilitation of limited oral opening have been tried such as surgeries, use of dynamic opening devices, magnetic devices, and modification of denture design. Here we present; a simplified technique and simple design for fabrication of maxillary hinged and mandibular hinged and sectional complete denture for a patient with restricted mouth opening due to oral submucous fibrosis.

  12. Capillary origami of micro-machined micro-objects: Bi-layer conductive hinges

    NARCIS (Netherlands)

    Legrain, A.B.H.; Berenschot, Johan W.; Tas, Niels Roelof; Abelmann, Leon

    2015-01-01

    Recently, we demonstrated controllable 3D self-folding by means of capillary forces of silicon-nitride micro-objects made of rigid plates connected to each other by flexible hinges (Legrain et al., 2014). In this paper, we introduce platinum electrodes running from the substrate to the plates over

  13. Design method for strut-beam connection in hinged frames

    OpenAIRE

    Cardenal Basté, Joan

    2011-01-01

    Glulam is almost exclusively the chosen material of timber frame structures. Of those, three-hinged (three-pin) portal frames are incomparably the most common type. Being both statically determinate and stable against horizontal forces in its own plane o er both practical (basic constructive details) and economical bene ts. The design of the haunch allows for various solutions: it can be curved with continuous laminates, nger jointed, jointed with steel dowels and slotted-i...

  14. The influence of material properties on plastic hinge rotational capacity and strength

    NARCIS (Netherlands)

    Steenbergen, H.M.G.M.; Bijlaard, F.S.K.; Daniels, B.J.

    1996-01-01

    In this article the effects of standardised material stress-strain behaviours on plastic hinge length, moment and rotational capacity are investigated using a specially developed computer program. Material properties are described using three standard post-yield stress-strain characteristics, as

  15. How Hinge Positioning in Cross-Country Ski Bindings Affect Exercise Efficiency, Cycle Characteristics and Muscle Coordination during Submaximal Roller Skiing

    Science.gov (United States)

    Bolger, Conor M.; Sandbakk, Øyvind; Ettema, Gertjan; Federolf, Peter

    2016-01-01

    The purposes of the current study were to 1) test if the hinge position in the binding of skating skis has an effect on gross efficiency or cycle characteristics and 2) investigate whether hinge positioning affects synergistic components of the muscle activation in six lower leg muscles. Eleven male skiers performed three 4-min sessions at moderate intensity while cross-country ski-skating and using a klapskate binding. Three different positions were tested for the binding’s hinge, ranging from the front of the first distal phalange to the metatarsal-phalangeal joint. Gross efficiency and cycle characteristics were determined, and the electromyographic (EMG) signals of six lower limb muscles were collected. EMG signals were wavelet transformed, normalized, joined into a multi-dimensional vector, and submitted to a principle component analysis (PCA). Our results did not reveal any changes to gross efficiency or cycle characteristics when altering the hinge position. However, our EMG analysis found small but significant effects of hinge positioning on muscle coordinative patterns (P skating klapskates. Finally, the within-subject results of the EMG analysis suggested that in addition to the between-subject effects, further forms of muscle coordination patterns appear to be employed by some, but not all participants. PMID:27203597

  16. Covalent protein modification with ISG15 via a conserved cysteine in the hinge region.

    Directory of Open Access Journals (Sweden)

    Veronika N Bade

    Full Text Available The ubiquitin-like protein ISG15 (interferon-stimulated gene of 15 kDa is strongly induced by type I interferons and displays antiviral activity. As other ubiquitin-like proteins (Ubls, ISG15 is post-translationally conjugated to substrate proteins by an isopeptide bond between the C-terminal glycine of ISG15 and the side chains of lysine residues in the substrates (ISGylation. ISG15 consists of two ubiquitin-like domains that are separated by a hinge region. In many orthologs, this region contains a single highly reactive cysteine residue. Several hundred potential substrates for ISGylation have been identified but only a few of them have been rigorously verified. In order to investigate the modification of several ISG15 substrates, we have purified ISG15 conjugates from cell extracts by metal-chelate affinity purification and immunoprecipitations. We found that the levels of proteins modified by human ISG15 can be decreased by the addition of reducing agents. With the help of thiol blocking reagents, a mutational analysis and miRNA mediated knock-down of ISG15 expression, we revealed that this modification occurs in living cells via a disulphide bridge between the substrates and Cys78 in the hinge region of ISG15. While the ISG15 activating enzyme UBE1L is conjugated by ISG15 in the classical way, we show that the ubiquitin conjugating enzyme Ubc13 can either be classically conjugated by ISG15 or can form a disulphide bridge with ISG15 at the active site cysteine 87. The latter modification would interfere with its function as ubiquitin conjugating enzyme. However, we found no evidence for an ISG15 modification of the dynamin-like GTPases MxA and hGBP1. These findings indicate that the analysis of potential substrates for ISG15 conjugation must be performed with great care to distinguish between the two types of modification since many assays such as immunoprecipitation or metal-chelate affinity purification are performed with little or no

  17. Cyclic plastic hinges with degradation effects for frame structures

    OpenAIRE

    Tidemann, Lasse; Krenk, Steen

    2017-01-01

    A model of cyclic plastic hinges in frame structures including degradation effects for stiffness and strength is developed. The model is formulated via potentials in terms of section forces. It consists of a yield surface, described in a generic format permitting representation of general convex shapes including corners, and a set of evolution equations based on an internal energy potential and a plastic flow potential. The form of these potentials is specified by five parameters for each gen...

  18. Analysis of Carbon Fiber Reinforced PEEK Hinge Mechanism Articulation Components in a Rotating Hinge Knee Design: A Comparison of In Vitro and Retrieval Findings.

    Science.gov (United States)

    Schierjott, Ronja A; Giurea, Alexander; Neuhaus, Hans-Joachim; Schwiesau, Jens; Pfaff, Andreas M; Utzschneider, Sandra; Tozzi, Gianluca; Grupp, Thomas M

    2016-01-01

    Carbon fiber reinforced poly-ether-ether-ketone (CFR-PEEK) represents a promising alternative material for bushings in total knee replacements, after early clinical failures of polyethylene in this application. The objective of the present study was to evaluate the damage modes and the extent of damage observed on CFR-PEEK hinge mechanism articulation components after in vivo service in a rotating hinge knee (RHK) system and to compare the results with corresponding components subjected to in vitro wear tests. Key question was if there were any similarities or differences between in vivo and in vitro damage characteristics. Twelve retrieved RHK systems after an average of 34.9 months in vivo underwent wear damage analysis with focus on the four integrated CFR-PEEK components and distinction between different damage modes and classification with a scoring system. The analysis included visual examination, scanning electron microscopy, and energy dispersive X-ray spectroscopy, as well as surface roughness and profile measurements. The main wear damage modes were comparable between retrieved and in vitro specimens ( n = 3), whereby the size of affected area on the retrieved components showed a higher variation. Overall, the retrieved specimens seemed to be slightly heavier damaged which was probably attributable to the more complex loading and kinematic conditions in vivo.

  19. Analysis of Carbon Fiber Reinforced PEEK Hinge Mechanism Articulation Components in a Rotating Hinge Knee Design: A Comparison of In Vitro and Retrieval Findings

    Directory of Open Access Journals (Sweden)

    Ronja A. Schierjott

    2016-01-01

    Full Text Available Carbon fiber reinforced poly-ether-ether-ketone (CFR-PEEK represents a promising alternative material for bushings in total knee replacements, after early clinical failures of polyethylene in this application. The objective of the present study was to evaluate the damage modes and the extent of damage observed on CFR-PEEK hinge mechanism articulation components after in vivo service in a rotating hinge knee (RHK system and to compare the results with corresponding components subjected to in vitro wear tests. Key question was if there were any similarities or differences between in vivo and in vitro damage characteristics. Twelve retrieved RHK systems after an average of 34.9 months in vivo underwent wear damage analysis with focus on the four integrated CFR-PEEK components and distinction between different damage modes and classification with a scoring system. The analysis included visual examination, scanning electron microscopy, and energy dispersive X-ray spectroscopy, as well as surface roughness and profile measurements. The main wear damage modes were comparable between retrieved and in vitro specimens (n=3, whereby the size of affected area on the retrieved components showed a higher variation. Overall, the retrieved specimens seemed to be slightly heavier damaged which was probably attributable to the more complex loading and kinematic conditions in vivo.

  20. Attitude Control of Nanosatellites by Paddle Motion Using Elastic Hinges Actuated by Shape Memory Alloy

    Science.gov (United States)

    Iai, Masafumi; Durali, Mohammad; Hatsuzawa, Takeshi

    Recent research has been extending the applications of small satellites called microsatellites, nanosatellites, or picosatellites. To further improve capability of those satellites, a lightweight, active attitude-control mechanism is needed. This paper proposes a concept of inertial orientation control, an attitude control method using movable solar arrays. This method is made suitable for nanosatellites by the use of shape memory alloy (SMA)-actuated elastic hinges and a simple maneuver generation algorithm. The combination of SMA and an elastic hinge allows the hinge to remain lightweight and free of frictional or rolling contacts. Changes in the shrinking and stretching speeds of the SMA were measured in a vacuum chamber. The proposed algorithm constructs a maneuver to achieve arbitrary attitude change by repeating simple maneuvers called unit maneuvers. Provided with three types of unit maneuvers, each degree of freedom of the satellite can be controlled independently. Such construction requires only simple calculations, making it a practical algorithm for a nanosatellite with limited computational capability. In addition, power generation variation caused by maneuvers was analyzed to confirm that a maneuver from any initial attitude to an attitude facing the sun was justifiable in terms of the power budget.

  1. Structure of a mouse immunoglobulin G that lacks the entire CH1 domain: Protein sequencing and small-angle X-ray scattering studies

    International Nuclear Information System (INIS)

    Igarashi, Takako; Tanaka, Toshiyuki; Nakanishi, Mamoru; Arata, Yoji; Sato, Mamoru; Katsube, Yukiteru; Takio, Koji

    1990-01-01

    The structure of a short-chain IgG2a antibody, which is a member of the family of mouse anti-dansyl switch variant antibodies with identical variable regions but different heavy-chain constant regions, is reported. Amino acid sequencing analyses have demonstrated that in the short-chain IgG2a antibody the entire C H 1 domain is deleted whereas the hinge region remains intact. Small-angle X-ray scattering data were collected for the short-chain IgG2a antibody and compared with those for the switch variant IgG1, IgG2a, and IgG2b antibodies with the normal heavy chain. It has been concluded that deletion of the C H 1 domain results in a large structural change and the short-chain IgG2a antibody possesses an elongated molecular shape with a much smaller hinge angle as compared with the normal IgG2a antibody that is a Y-shaped molecule

  2. Educational Entrepreneurship (EE: Delineating and Highlighting Its Domain, Importance and Feasibility in Uganda’s Context

    Directory of Open Access Journals (Sweden)

    Genza Musoke Gyaviira

    2018-02-01

    Full Text Available Although in many countries government financial support for education is dwindling, not many educational institutions have succeeded in devising internal mechanisms and practices to enable them to continuously deliver quality education in quantity. Might the application of certain entrepreneurial strategies in educational management perhaps help to make a difference? What is educational entrepreneurship (EE? How feasible is EE in a developing world education landscape like that of Uganda? Which challenges must EE surmount before it can envisage success? Using literature review methodology, this study attempted to find answers to such questions. Its aim was to delineate the EE domain and to highlight both its importance and feasibility in Uganda’s context. The study makes two important revelations; first, that indeed EE is clouded in conceptual mishmash, hence need for more scholarly attention on the subject; second, that however salvaging EE can be to struggling educational institutions, it is not without challenges – even apparent contradictions – hence preference for a “moderate risk” approach to entrepreneurship within educational institutions.    

  3. Role for the MED21-MED7 Hinge in Assembly of the Mediator-RNA Polymerase II Holoenzyme*

    Science.gov (United States)

    Sato, Shigeo; Tomomori-Sato, Chieri; Tsai, Kuang-Lei; Yu, Xiaodi; Sardiu, Mihaela; Saraf, Anita; Washburn, Michael P.; Florens, Laurence; Asturias, Francisco J.; Conaway, Ronald C.

    2016-01-01

    Mediator plays an integral role in activation of RNA polymerase II (Pol II) transcription. A key step in activation is binding of Mediator to Pol II to form the Mediator-Pol II holoenzyme. Here, we exploit a combination of biochemistry and macromolecular EM to investigate holoenzyme assembly. We identify a subset of human Mediator head module subunits that bind Pol II independent of other subunits and thus probably contribute to a major Pol II binding site. In addition, we show that binding of human Mediator to Pol II depends on the integrity of a conserved “hinge” in the middle module MED21-MED7 heterodimer. Point mutations in the hinge region leave core Mediator intact but lead to increased disorder of the middle module and markedly reduced affinity for Pol II. These findings highlight the importance of Mediator conformation for holoenzyme assembly. PMID:27821593

  4. Nanomechanics of the substrate binding domain of Hsp70 determine its allosteric ATP-induced conformational change.

    Science.gov (United States)

    Mandal, Soumit Sankar; Merz, Dale R; Buchsteiner, Maximilian; Dima, Ruxandra I; Rief, Matthias; Žoldák, Gabriel

    2017-06-06

    Owing to the cooperativity of protein structures, it is often almost impossible to identify independent subunits, flexible regions, or hinges simply by visual inspection of static snapshots. Here, we use single-molecule force experiments and simulations to apply tension across the substrate binding domain (SBD) of heat shock protein 70 (Hsp70) to pinpoint mechanical units and flexible hinges. The SBD consists of two nanomechanical units matching 3D structural parts, called the α- and β-subdomain. We identified a flexible region within the rigid β-subdomain that gives way under load, thus opening up the α/β interface. In exactly this region, structural changes occur in the ATP-induced opening of Hsp70 to allow substrate exchange. Our results show that the SBD's ability to undergo large conformational changes is already encoded by passive mechanics of the individual elements.

  5. Determination of Elevator and Rudder Hinge Forces on the Learjet Model 55 Aircraft

    Science.gov (United States)

    Boroughs, R. R.; Padmanabhan, V.

    1983-01-01

    The empennage structure on the Learjet 55 aircraft was quite similar to the empennage structure on earlier Learjet models. However, due to an important structural change in the vertical fin along with the new loads environment on the 50 series aircraft, a structural test was required on the vertical fin, but the horizontal tail was substantiated by a comparative analysis with previous tests. NASTRAN analysis was used to investigate empennage deflections, stress levels, and control surface hinge forces. The hinge force calculations were made with the control surfaces in the deflected as well as undeflected configurations. A skin panel buckling analysis was also performed, and the non-linear effects of buckling were simulated in the NASTRAN model to more accurately define internal loads and stress levels. Comparisons were then made between the Model 55 and the Model 35/36 stresses and internal forces to determine which components were qualified by previous tests. Some of the methods and techniques used in this analysis are described.

  6. Structure of a mouse immunoglobulin G that lacks the entire C sub H 1 domain: Protein sequencing and small-angle X-ray scattering studies

    Energy Technology Data Exchange (ETDEWEB)

    Igarashi, Takako; Tanaka, Toshiyuki; Nakanishi, Mamoru; Arata, Yoji (Univ. of Tokyo (Japan)); Sato, Mamoru; Katsube, Yukiteru (Osaka Univ. (Japan)); Takio, Koji (Institute of Physical and Chemical Research, Saitama (Japan))

    1990-06-19

    The structure of a short-chain IgG2a antibody, which is a member of the family of mouse anti-dansyl switch variant antibodies with identical variable regions but different heavy-chain constant regions, is reported. Amino acid sequencing analyses have demonstrated that in the short-chain IgG2a antibody the entire C{sub H}1 domain is deleted whereas the hinge region remains intact. Small-angle X-ray scattering data were collected for the short-chain IgG2a antibody and compared with those for the switch variant IgG1, IgG2a, and IgG2b antibodies with the normal heavy chain. It has been concluded that deletion of the C{sub H}1 domain results in a large structural change and the short-chain IgG2a antibody possesses an elongated molecular shape with a much smaller hinge angle as compared with the normal IgG2a antibody that is a Y-shaped molecule.

  7. Solution structure of the Grb2 SH2 domain complexed with a high-affinity inhibitor

    International Nuclear Information System (INIS)

    Ogura, Kenji; Shiga, Takanori; Yokochi, Masashi; Yuzawa, Satoru; Burke, Terrence R.; Inagaki, Fuyuhiko

    2008-01-01

    The solution structure of the growth factor receptor-bound protein 2 (Grb2) SH2 domain complexed with a high-affinity inhibitor containing a non-phosphorus phosphate mimetic within a macrocyclic platform was determined by nuclear magnetic resonance (NMR) spectroscopy. Unambiguous assignments of the bound inhibitor and intermolecular NOEs between the Grb2 SH2 domain and the inhibitor was accomplished using perdeuterated Grb2 SH2 protein. The well-defined solution structure of the complex was obtained and compared to those by X-ray crystallography. Since the crystal structure of the Grb2 SH2 domain formed a domain-swapped dimer and several inhibitors were bound to a hinge region, there were appreciable differences between the solution and crystal structures. Based on the binding interactions between the inhibitor and the Grb2 SH2 domain in solution, we proposed a design of second-generation inhibitors that could be expected to have higher affinity

  8. Deployment Analysis of a Simple Tape-Spring Hinge Using Probabilistic Methods

    Science.gov (United States)

    Lyle, Karen H.; Horta, Lucas G.

    2012-01-01

    Acceptance of new deployable structures architectures and concepts requires validated design methods to minimize the expense involved with technology validation flight testing. Deployable concepts for large lightweight spacecraft include booms, antennae, and masts. This paper explores the implementation of probabilistic methods in the design process for the deployment of a strain-energy mechanism, specifically a simple tape-spring hinge. Strain-energy mechanisms are attractive for deployment in very lightweight systems because they do not require the added mass and complexity associated with motors and controllers. However, designers are hesitant to include free deployment, strain-energy mechanisms because of the potential for uncontrolled behavior. In the example presented here, the tapespring cross-sectional dimensions have been varied and a target displacement during deployment has been selected as the design metric. Specifically, the tape-spring should reach the final position in the shortest time with the minimal amount of overshoot and oscillations. Surrogate models have been used to reduce computational expense. Parameter values to achieve the target response have been computed and used to demonstrate the approach. Based on these results, the application of probabilistic methods for design of a tape-spring hinge has shown promise as a means of designing strain-energy components for more complex space concepts.

  9. [Localization and registration of the hinge axis in black Africans].

    Science.gov (United States)

    Assi, K D; N'Guessan, K S; N'Dindin, C; Bamba, A

    2003-06-01

    The study of the cinematic method using "SAM" and "Quick Axis of FAG" added to mandibular condyle palpation for the hinge axis limited points, show that the Black Africans mandibular condyle rotation axis position is higher (3.5 mm) and backer (2 mm) than the Caucasians. The axial points are located to between 11 and 12 mm in front of the tragus and between 7 and 8 mm below on the perpendicular line to the furrow defining the tragus superior side to the Ectocanthus.

  10. Amino acid changes within the E protein hinge region that affect dengue virus type 2 infectivity and fusion

    International Nuclear Information System (INIS)

    Butrapet, Siritorn; Childers, Thomas; Moss, Kelley J.; Erb, Steven M.; Luy, Betty E.; Calvert, Amanda E.; Blair, Carol D.; Roehrig, John T.; Huang, Claire Y.-H.

    2011-01-01

    Fifteen mutant dengue viruses were engineered and used to identify AAs in the molecular hinge of the envelope protein that are critical to viral infection. Substitutions at Q52, A54, or E133 reduced infectivity in mammalian cells and altered the pH threshold of fusion. Mutations at F193, G266, I270, or G281 affected viral replication in mammalian and mosquito cells, but only I270W had reduced fusion activity. T280Y affected the pH threshold for fusion and reduced replication in C6/36 cells. Three different mutations at L135 were lethal in mammalian cells. Among them, L135G abrogated fusion and reduced replication in C6/36 cells, but only slightly reduced the mosquito infection rate. Conversely, L135W replicated well in C6/36 cells, but had the lowest mosquito infection rate. Possible interactions between hinge residues 52 and 277, or among 53, 135, 170, 186, 265, and 276 required for hinge function were discovered by sequence analysis to identify compensatory mutations.

  11. Cohesive cracked-hinge model for simulation of fracture in one-way slabs on grade

    DEFF Research Database (Denmark)

    Skar, Asmus; Poulsen, Peter Noe; Olesen, John Forbes

    2017-01-01

    Numerical analysis of slab on grade structures subjected to mechanical loads is a complex matter often requiring computationally expensive models. In order to develop a simplified and general concept for non-linear analysis of slab on grade structures, this paper presents a cohesive cracked-hinge...

  12. Hinge-deleted IgG4 blocker therapy for acetylcholine receptor myasthenia gravis in rhesus monkeys.

    Science.gov (United States)

    Losen, Mario; Labrijn, Aran F; van Kranen-Mastenbroek, Vivianne H; Janmaat, Maarten L; Haanstra, Krista G; Beurskens, Frank J; Vink, Tom; Jonker, Margreet; 't Hart, Bert A; Mané-Damas, Marina; Molenaar, Peter C; Martinez-Martinez, Pilar; van der Esch, Eline; Schuurman, Janine; de Baets, Marc H; Parren, Paul W H I

    2017-04-20

    Autoantibodies against ion channels are the cause of numerous neurologic autoimmune disorders. Frequently, such pathogenic autoantibodies have a restricted epitope-specificity. In such cases, competing antibody formats devoid of pathogenic effector functions (blocker antibodies) have the potential to treat disease by displacing autoantibodies from their target. Here, we have used a model of the neuromuscular autoimmune disease myasthenia gravis in rhesus monkeys (Macaca mulatta) to test the therapeutic potential of a new blocker antibody: MG was induced by passive transfer of pathogenic acetylcholine receptor-specific monoclonal antibody IgG1-637. The effect of the blocker antibody (IgG4Δhinge-637, the hinge-deleted IgG4 version of IgG1-637) was assessed using decrement measurements and single-fiber electromyography. Three daily doses of 1.7 mg/kg IgG1-637 (cumulative dose 5 mg/kg) induced impairment of neuromuscular transmission, as demonstrated by significantly increased jitter, synaptic transmission failures (blockings) and a decrease in the amplitude of the compound muscle action potentials during repeated stimulations (decrement), without showing overt symptoms of muscle weakness. Treatment with three daily doses of 10 mg/kg IgG4Δhinge-637 significantly reduced the IgG1-637-induced increase in jitter, blockings and decrement. Together, these results represent proof-of principle data for therapy of acetylcholine receptor-myasthenia gravis with a monovalent antibody format that blocks binding of pathogenic autoantibodies.

  13. Effects of opioids in the formalin test in the Speke's hinged tortoise (Kinixy's spekii)

    DEFF Research Database (Denmark)

    Wambugu, SN; Towett, PK; Kiama, SG

    2010-01-01

    decrease in the duration of limb retraction in the formalin test. The anti-nociceptive effects were naloxone (5 mg/kg) reversible. The data suggest that the formalin test is a good test for studying nociception and anti-nociception in tortoises and that the opioidergic system plays a role in the control......Little is known about analgesia in lower vertebrates such as the Speke's hinged tortoise (Kinixy's spekii), yet of late they are increasingly being adopted as pets. The effects of morphine (5, 7.5, 10 and 20 mg/kg), pethidine (10, 20, and 50 mg/kg) and naloxone (5 mg/kg) on nociception induced...... by the formalin test (12.5%, 100 microL) were studied in the Speke's hinged tortoise. Formalin induced a monophasic limb retraction behavioural response and its duration was recorded. The behaviour lasted for 16.4 +/- 0.8 min. Morphine (7.5, 10 and 20 mg/kg) and pethidine (20 and 50 mg/kg) induced significant...

  14. Amino acid sequence requirements in the human IgA1 hinge for cleavage by streptococcal IgA1 proteases

    DEFF Research Database (Denmark)

    Senior, BW; Batten, MR; Kilian, Mogens

    2002-01-01

    All the IgA1 proteases of the different pathogenic species of Streptococcus cleave the hinge of the alpha chain of human IgA1 only at one proline-threonine peptide bond. In order to study the importance of these amino acids for cleavage, several hinge mutant recombinant IgA1 antibodies were const...... constructed. The mutations were found to be without major effect upon the structure or functional abilities of the antibodies. However, they had a major effect upon their sensitivity to cleavage by some of the IgA1 proteases....

  15. Treatment of neglected elbow dislocations with the help of hinged external fixator: Report of two cases

    Directory of Open Access Journals (Sweden)

    Özgür Karakoyun

    2014-06-01

    Full Text Available Elbow dislocations are cases that have to be treated in emergency conditions. Neglected elbow dislocations are seen very rarely and the treatment of such cases are more complicated than acute cases. We present two cases of neglected elbow dislocations treated with open reduction and hinged external fixators. Case 1: 23 year old female patient had a neglected posterior dislocation of left elbow with ipsilateral humeral shaft fracture caused by car accident. The patient was treated after 3 months of initial trauma. We have performed open reduction for the joint. After that we fixed the joint whit a hinged external fixator. The humeral shaft fracture was also fixed with the components of the external fixator. Case 2: 33 year male patient had a large bone and soft tissue defect around the left elbow accompanying with neglected medial elbow dislocation. He presented to our clinic with a delay of 2 months. The patient was treated with open reduction and hinged external fixator after reconstruction of bone defect of distal humerus. Conclusion: The treatment of neglected cases is quite challenging. Open reduction and external fixation has satisfactory results in treatment of late cases of elbow dislocation with the possibility of early rehabilitation. This method can be considered as an option for such cases. J Clin Exp Invest 2014; 5 (2: 443-446

  16. The SH2 Domain Regulates c-Abl Kinase Activation by a Cyclin-Like Mechanism and Remodulation of the Hinge Motion

    OpenAIRE

    Dölker, N.; Górna, M. W.; Sutto, L.; Torralba, A. S.; Superti-Furga, G.; Gervasio, F. L.

    2014-01-01

    Regulation of the c-Abl (ABL1) tyrosine kinase is important because of its role in cellular signaling, and its relevance in the leukemiogenic counterpart (BCR-ABL). Both auto-inhibition and full activation of c-Abl are regulated by the interaction of the catalytic domain with the Src Homology 2 (SH2) domain. The mechanism by which this interaction enhances catalysis is not known. We combined computational simulations with mutagenesis and functional analysis to find that the SH2 domain conveys...

  17. The Intrinsically Disordered Domain of the Antitoxin Phd Chaperones the Toxin Doc against Irreversible Inactivation and Misfolding*

    Science.gov (United States)

    De Gieter, Steven; Konijnenberg, Albert; Talavera, Ariel; Butterer, Annika; Haesaerts, Sarah; De Greve, Henri; Sobott, Frank; Loris, Remy; Garcia-Pino, Abel

    2014-01-01

    The toxin Doc from the phd/doc toxin-antitoxin module targets the cellular translation machinery and is inhibited by its antitoxin partner Phd. Here we show that Phd also functions as a chaperone, keeping Doc in an active, correctly folded conformation. In the absence of Phd, Doc exists in a relatively expanded state that is prone to dimerization through domain swapping with its active site loop acting as hinge region. The domain-swapped dimer is not capable of arresting protein synthesis in vitro, whereas the Doc monomer is. Upon binding to Phd, Doc becomes more compact and is secured in its monomeric state with a neutralized active site. PMID:25326388

  18. Structural mapping of the coiled-coil domain of a bacterial condensin and comparative analyses across all domains of life suggest conserved features of SMC proteins.

    Science.gov (United States)

    Waldman, Vincent M; Stanage, Tyler H; Mims, Alexandra; Norden, Ian S; Oakley, Martha G

    2015-06-01

    The structural maintenance of chromosomes (SMC) proteins form the cores of multisubunit complexes that are required for the segregation and global organization of chromosomes in all domains of life. These proteins share a common domain structure in which N- and C- terminal regions pack against one another to form a globular ATPase domain. This "head" domain is connected to a central, globular, "hinge" or dimerization domain by a long, antiparallel coiled coil. To date, most efforts for structural characterization of SMC proteins have focused on the globular domains. Recently, however, we developed a method to map interstrand interactions in the 50-nm coiled-coil domain of MukB, the divergent SMC protein found in γ-proteobacteria. Here, we apply that technique to map the structure of the Bacillus subtilis SMC (BsSMC) coiled-coil domain. We find that, in contrast to the relatively complicated coiled-coil domain of MukB, the BsSMC domain is nearly continuous, with only two detectable coiled-coil interruptions. Near the middle of the domain is a break in coiled-coil structure in which there are three more residues on the C-terminal strand than on the N-terminal strand. Close to the head domain, there is a second break with a significantly longer insertion on the same strand. These results provide an experience base that allows an informed interpretation of the output of coiled-coil prediction algorithms for this family of proteins. A comparison of such predictions suggests that these coiled-coil deviations are highly conserved across SMC types in a wide variety of organisms, including humans. © 2015 Wiley Periodicals, Inc.

  19. Ranking Highlights in Personal Videos by Analyzing Edited Videos.

    Science.gov (United States)

    Sun, Min; Farhadi, Ali; Chen, Tseng-Hung; Seitz, Steve

    2016-11-01

    We present a fully automatic system for ranking domain-specific highlights in unconstrained personal videos by analyzing online edited videos. A novel latent linear ranking model is proposed to handle noisy training data harvested online. Specifically, given a targeted domain such as "surfing," our system mines the YouTube database to find pairs of raw and their corresponding edited videos. Leveraging the assumption that an edited video is more likely to contain highlights than the trimmed parts of the raw video, we obtain pair-wise ranking constraints to train our model. The learning task is challenging due to the amount of noise and variation in the mined data. Hence, a latent loss function is incorporated to mitigate the issues caused by the noise. We efficiently learn the latent model on a large number of videos (about 870 min in total) using a novel EM-like procedure. Our latent ranking model outperforms its classification counterpart and is fairly competitive compared with a fully supervised ranking system that requires labels from Amazon Mechanical Turk. We further show that a state-of-the-art audio feature mel-frequency cepstral coefficients is inferior to a state-of-the-art visual feature. By combining both audio-visual features, we obtain the best performance in dog activity, surfing, skating, and viral video domains. Finally, we show that impressive highlights can be detected without additional human supervision for seven domains (i.e., skating, surfing, skiing, gymnastics, parkour, dog activity, and viral video) in unconstrained personal videos.

  20. Design and Analysis of Wind Turbine Rotors Using Hinged Structures and Rods

    Science.gov (United States)

    Lu, Hongya; Zeng, Pan; Lei, Liping

    2018-03-01

    Light weight and high stiffness are key design factors in ensuring cost effectiveness and reliability of wind turbines, especially for the inboard region of the rotor blades. In this study, several novel designs were developed to improve the mechanical performance of the rotor. Experiments were performed on an isolated blade incorporating the new features of a hinged structure and rods. The results validated the effectiveness of these features at alleviating the root-bending moment of the blade under varying wind loads and enhancing the stiffness of the blade. A numerical investigation was carried out to further examine the bending moment distribution, shear and axial force, and rod tension of these novel rotor designs under uniform loads. Longitudinal geometrical variations of the blade were considered in the model. Results showed that two designs realized a favorable bending moment distribution and improved the modal frequencies of the edgewise modes: bisymmetrical rods on a single-hinged structure and interveined symmetrical rods on a cantilevered structure. However, these designs have different deformation mechanisms. In addition, the first group of edgewise modal frequencies of these two designs were improved compared with the traditional rotor design. Their potential values in the application to the design of a lightweight, high-stiffness, and reliable wind turbine rotor were discussed.

  1. The Impact of the ‘Austrian’ Mutation of the Amyloid Precursor Protein Transmembrane Helix is Communicated to the Hinge Region

    DEFF Research Database (Denmark)

    Stelzer, Walter; Scharnagl, Christina; Leurs, Ulrike

    2016-01-01

    The transmembrane helix of the amyloid precursor protein is subject to proteolytic cleavages by γ-secretase at different sites resulting in Aβ peptides of different length and toxicity. A number of point mutations within this transmembrane helix alter the cleavage pattern thus enhancing production...... destabilizes amide hydrogen bonds in the hinge which connects dimerization and cleavage regions. Weaker intrahelical hydrogen bonds at the hinge may enhance helix bending and thereby affect recognition of the transmembrane substrate by the enzyme and/or presentation of its cleavage sites to the catalytic cleft....

  2. Role of an anatomically contoured plate and metal block for balanced stability between the implant and lateral hinge in open-wedge high-tibial osteotomy.

    Science.gov (United States)

    Jang, Young Woong; Lim, DoHyung; Seo, Hansol; Lee, Myung Chul; Lee, O-Sung; Lee, Yong Seuk

    2018-07-01

    Open-wedge high tibial osteotomy (OWHTO) is a well-established surgical option for medial compartment osteoarthritis of the varus knee. The initial strength of the fixation plate is critical for successful correction maintenance and healing of the osteotomy site. This study was conducted to verify if a newly designed anatomical plate (LCfit) improves the stability of both the medial implant and lateral hinge area, as well as to evaluate how the metal block contributes to both medial and lateral stability. A finite element (FE) tibial model was combined with TomoFix plate, a LCfit plate with and without a metal block. Data analysis was conducted to evaluate the balanced stability, which refers to the enforced lateral stability resulting from redistribution of overall stress. We assessed the balanced stability of the medial implant and lateral hinge area in three cases using the same Sawbones and loads using the tibia FE model. The LCfit plate reduced stress by 23.1% at the lateral hinge compared to the TomoFix plate (TomoFix vs. LCfit: 34.2 ± 23.3 MPa vs. 26.3 ± 17.5 MPa). The LCfit plate with a metal block reduced stress by 40.1% at the medial plate (210.1 ± 64.2 MPa vs. 125.8 ± 65.7 MPa) and by 31.2% (26.3 ± 17.5 MPa vs. 18.1 ± 12.1 MPa) at the lateral hinge area compared to the reduction using the LCfit plate without a metal block. The newly designed fixation system for OWHTO balanced the overall stress distribution and reduced stress at the lateral hinge area compared to that using a conventional fixation system. The addition of the metal block showed additional benefits for balanced stability between the medial implant and lateral hinge area. However, this conclusion could only be drawn using the FE model in this study. Therefore, further clinical studies are necessary to reveal the clinical effect of reduced lateral stress on the occurrence of the lateral hinge fracture and the biologic effect of the metal block on the

  3. A Study on the Modeling of the Oil Damper in an Auto-Door Hinge

    International Nuclear Information System (INIS)

    Ha, Kwang Soon; Kim, Jong Tae; Kim, Hwan Yeol

    2009-11-01

    An auto-door hinge, which is one of the automatic door-closing apparatuses, has been widely used to prevent fire propagations in living or commercial buildings. The auto-door hinge consists of a spring to accumulate power for closing a door and an oil damper to control door-closing velocity. To predict and optimize the temporal door behavior during the door-closing period, the auto-door closing system was modeled as a second order-damping system. And a damping coefficient of the oil damper was also theoretically modeled by analyzing Newtonian, incompressible, viscous flow through an oil passage between a oil control rod and a oil piston body. The temporal door behaviors during the door-closing period were predicted with respect to the gap distance of the oil passage, oil viscosity, and pre-compressing of the spring. Temporal door behavior measurement method using an encoder system was also developed to validate the modelling on the oil damping system. As using the developed test apparatus, the temporal door position, velocity, and rotational torque were measured, and the modelling method was evaluated

  4. Role of the hinge region of glucocorticoid receptor for HEXIM1-mediated transcriptional repression

    International Nuclear Information System (INIS)

    Yoshikawa, Noritada; Shimizu, Noriaki; Sano, Motoaki; Ohnuma, Kei; Iwata, Satoshi; Hosono, Osamu; Fukuda, Keiichi; Morimoto, Chikao

    2008-01-01

    We previously reported that HEXIM1 (hexamethylene bisacetamide-inducible protein 1), which suppresses transcription elongation via sequestration of positive transcription elongation factor b (P-TEFb) using 7SK RNA as a scaffold, directly associates with glucocorticoid receptor (GR) to suppress glucocorticoid-inducible gene activation. Here, we revealed that the hinge region of GR is essential for its interaction with HEXIM1, and that oxosteroid receptors including GR show sequence homology in their hinge region and interact with HEXIM1, whereas the other members of nuclear receptors do not. We also showed that HEXIM1 suppresses GR-mediated transcription in two ways: sequestration of P-TEFb by HEXIM1 and direct interaction between GR and HEXIM1. In contrast, peroxisome proliferator-activated receptor γ-dependent gene expression is negatively modulated by HEXIM1 solely via sequestration of P-TEFb. We, therefore, conclude that HEXIM1 may act as a gene-selective transcriptional regulator via direct interaction with certain transcriptional regulators including GR and contribute to fine-tuning of, for example, glucocorticoid-mediated biological responses

  5. A Study on the Modeling of the Oil Damper in an Auto-Door Hinge

    Energy Technology Data Exchange (ETDEWEB)

    Ha, Kwang Soon; Kim, Jong Tae; Kim, Hwan Yeol

    2009-11-15

    An auto-door hinge, which is one of the automatic door-closing apparatuses, has been widely used to prevent fire propagations in living or commercial buildings. The auto-door hinge consists of a spring to accumulate power for closing a door and an oil damper to control door-closing velocity. To predict and optimize the temporal door behavior during the door-closing period, the auto-door closing system was modeled as a second order-damping system. And a damping coefficient of the oil damper was also theoretically modeled by analyzing Newtonian, incompressible, viscous flow through an oil passage between a oil control rod and a oil piston body. The temporal door behaviors during the door-closing period were predicted with respect to the gap distance of the oil passage, oil viscosity, and pre-compressing of the spring. Temporal door behavior measurement method using an encoder system was also developed to validate the modelling on the oil damping system. As using the developed test apparatus, the temporal door position, velocity, and rotational torque were measured, and the modelling method was evaluated.

  6. Good Functional Recovery of Complex Elbow Dislocations Treated With Hinged External Fixation: A Multicenter Prospective Study

    NARCIS (Netherlands)

    G.I.T. Iordens (Gijs); D. den Hartog (Dennis); E.M.M. van Lieshout (Esther); W.E. Tuinebreijer (Wim); J. de Haan (Jeroen); P. Patka (Peter); M.H.J. Verhofstad (Michiel); N.W.L. Schep (Niels)

    2015-01-01

    textabstractBackground: After a complex dislocation, some elbows remain unstable after closed reduction or fracture treatment. Function after treatment with a hinged external fixator theoretically allows collateral ligaments to heal without surgical reconstruction. However, there is a lack of

  7. Good Functional Recovery of Complex Elbow Dislocations Treated With Hinged External Fixation: A Multicenter Prospective Study

    NARCIS (Netherlands)

    Iordens, Gijs I. T.; den Hartog, Dennis; van Lieshout, Esther M. M.; Tuinebreijer, Wim E.; de Haan, Jeroen; Patka, Peter; Verhofstad, Michael H. J.; Schep, Niels W. L.; Bronkhorst, M. W. G. A.; de Vries, M. R.; Goslings, J. C.; Rhemrev, S. J.; Roukema, G. R.; van der Meulen, H. G. W. M.; Verleisdonk, E. J. M. M.; Vroemen, J. P. A. M.; Wittich, Ph

    2015-01-01

    After a complex dislocation, some elbows remain unstable after closed reduction or fracture treatment. Function after treatment with a hinged external fixator theoretically allows collateral ligaments to heal without surgical reconstruction. However, there is a lack of prospective studies that

  8. Akt1 binds focal adhesion kinase via the Akt1 kinase domain independently of the pleckstrin homology domain.

    Science.gov (United States)

    Basson, M D; Zeng, B; Wang, S

    2015-10-01

    Akt1 and focal adhesion kinase (FAK) are protein kinases that play key roles in normal cell signaling. Individually, aberrant expression of these kinases has been linked to a variety of cancers. Together, Akt1/FAK interactions facilitate cancer metastasis by increasing cell adhesion under conditions of increased extracellular pressure. Pathological and iatrogenic sources of pressure arise from tumor growth against constraining stroma or direct perioperative manipulation. We previously reported that 15 mmHg increased extracellular pressure causes Akt1 to both directly interact with FAK and to phosphorylate and activate it. We investigated the nature of the Akt1/FAK binding by creating truncations of recombinant FAK, conjugated to glutathione S-transferase (GST), to pull down full-length Akt1. Western blots probing for Akt1 showed that FAK/Akt1 binding persisted in FAK truncations consisting of only amino acids 1-126, FAK(NT1), which contains the F1 subdomain of its band 4.1, ezrin, radixin, and moesin (FERM) domain. Using FAK(NT1) as bait, we then pulled down truncated versions of recombinant Akt1 conjugated to HA (human influenza hemagglutinin). Probes for GST-FAK(NT1) showed Akt1-FAK binding to occur in the absence of the both the Akt1 (N)-terminal pleckstrin homology (PH) domain and its adjacent hinge region. The Akt1 (C)-terminal regulatory domain was equally unnecessary for Akt1/FAK co-immunoprecipitation. Truncations involving the Akt1 catalytic domain showed that the domain by itself was enough to pull down FAK. Additionally, a fragment spanning from the PH domain to half way through the catalytic domain demonstrated increased FAK binding compared to full length Akt1. These results begin to delineate the Akt1/FAK interaction and can be used to manipulate their force-activated signal interactions. Furthermore, the finding that the N-terminal half of the Akt1 catalytic domain binds so strongly to FAK when cleaved from the rest of the protein may suggest a means

  9. Comprehensive Analysis of the Therapeutic IgG4 Antibody Pembrolizumab: Hinge Modification Blocks Half Molecule Exchange In Vitro and In Vivo.

    Science.gov (United States)

    Yang, Xiaoyu; Wang, Fengqiang; Zhang, Ying; Wang, Larry; Antonenko, Svetlana; Zhang, Shuli; Zhang, Yi Wei; Tabrizifard, Mohammad; Ermakov, Grigori; Wiswell, Derek; Beaumont, Maribel; Liu, Liming; Richardson, Daisy; Shameem, Mohammed; Ambrogelly, Alexandre

    2015-12-01

    IgG4 antibodies are evolving as an important class of cancer immunotherapies. However, human IgG4 can undergo Fab arm (half molecule) exchange with other IgG4 molecules in vivo. The hinge modification by a point mutation (S228P) prevents half molecule exchange of IgG4. However, the experimental confirmation is still expected by regulatory agencies. Here, we report for the first time the extensive analysis of half molecule exchange for a hinge-modified therapeutic IgG4 molecule, pembrolizumab (Keytruda) targeting programmed death 1 (PD1) receptor that was approved for advanced melanoma. Studies were performed in buffer or human serum using multiple exchange partners including natalizumab (Tysabri) and human IgG4 pool. Formation of bispecific antibodies was monitored by fluorescence resonance energy transfer, exchange with Fc fragments, mixed mode chromatography, immunoassays, and liquid chromatography-mass spectrometry. The half molecule exchange was also examined in vivo in SCID (severe combined immunodeficiency) mice. Both in vitro and in vivo results indicate that the hinge modification in pembrolizumab prevented half molecule exchange, whereas the unmodified counterpart anti-PD1 wt showed active exchange activity with other IgG4 antibodies or self-exchange activity with its own molecules. Our work, as an example expected for meeting regulatory requirements, contributes to establish without ambiguity that hinge-modified IgG4 antibodies are suitable for biotherapeutic applications. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  10. Characterization of flexure hinges for the French watt balance experiment

    Directory of Open Access Journals (Sweden)

    Pinot Patrick

    2014-01-01

    Full Text Available In the French watt balance experiment, the translation and rotation functions must have no backlash, no friction, nor the need for lubricants. In addition errors in position and movement must be below 100 nm. Flexure hinges can meet all of these criteria. Different materials, profile shapes and machining techniques have been studied. The flexure pivots have been characterized using three techniques: 1 an optical microscope and, if necessary, a SEM to observe the surface inhomogeneities; 2 a mass comparator to determine the bending stiffness of unloaded pivots; 3 a loaded beam oscillating freely under vacuum to study the dynamic behavior of loaded pivots.

  11. Formation of vortex pairs with hinged rigid flaps at the nozzle exit

    Science.gov (United States)

    Das, Prashant; Govardhan, Raghuraman; Arakeri, Jaywant

    2013-11-01

    Biological flows related to aquatic propulsion using pulsed jets, or flow through the valves in a human heart, have received considerable attention in the last two decades. Both these flows are associated with starting jets that occur through biological tissue/membranes that are flexible. Motivated by these flows, we explore in the present work, the effect of passive flexibility of the nozzle exit on vortex generation from a starting jet. The starting jet is generated using a two-dimensional piston cylinder mechanism, the cross-section of the cylinder being rectangular with large aspect ratio. The fluid is pushed out of this cylinder or channel using a computer controlled piston. We introduce flexibility at the channel exit by hinging rigid flaps, which are initially parallel to the channel. The hinge used is such that it provides negligible stiffness or damping, thus allowing for the maximum opening of the flaps due to fluid forces. Using this system, we study both the flap kinematics and the vorticity dynamics downstream of the channel exit. Visualizations show large flap motions as the piston starts and this dramatically changes the vorticity distribution downstream of the flaps, with the formation of up to three different kinds of vortex pairs. This idealized configuration opens new opportunities to look at the effect of flexibility in such biological flows.

  12. Investigation of the Three-Dimensional Hinge Moment Characteristics Generated by the ONERA-M6 Wing with an Aileron

    Directory of Open Access Journals (Sweden)

    G. Q. Zhang

    2013-01-01

    Full Text Available The hinge moment characteristics for ONERA-M6 wing with aileron configuration have been investigated numerically based on the different gaps and deflecting angles. The results show that the effects on the wing made by the deflecting aileron are notable. Comparing with the nonaileron case, the chordwise pressure coefficient distribution for the wing with aileron has shown the totally different trends. The small gap can force the air flow through and form the extremely strong spraying flow. It can directly destroy the previously formed leading edge vortex (LEV. Due to the presence of the positive deflecting angle, the trailing edge vortex (TEV will begin to generate at the trailing edge of the aileron. The induced secondary LEV will be mixed with the developing TEVs and form the stronger TEVs at the downstream position. Comparing with the subsonic flow, the curve for the supersonic flow has shown a good linear. The corresponding hinge moments are also extremely sensitive to the changing angle of attack, and the slope of curves is also bigger than that of the subsonic flow. The bigger gap and deflecting angle can result in the curve of hinge moment bending upward at high angle of attack. The corresponding pressure cloud and streamlines have also been obtained computationally and analyzed in detail.

  13. Study on Utilization of LVL Sengon (Paraserianthes falcataria for Three-Hinged Gable Frame Structures

    Directory of Open Access Journals (Sweden)

    Ali Awaludin

    2016-07-01

    Full Text Available This study focuses on the utilization of non-prismatic LVL members of wood species Sengon (Paraserianthes falcataria for three-hinged gable frame structures. This wood species matures in 6 to 8 years, and the innovative application as LVL product for these structures is evaluated. A full-scale model of a beam-column connection is produced and tested to validate the moment-rotation response predicted by the numerical study using ABAQUS. The FEM results showed a linear-elastic moment-rotation curve response up to a joint rotation of 0.015 radians which is in very good agreement with the experiment. This validated FE model for the beam-column joint was further utilized to generate predictions for the moment-rotation relation using different bolt diameters and configurations. The last part of this study presents an evaluation of the maximum load bearing capacity of three-hinged gable frame timber structures considering a rigid and semi-rigid beam-column joint model. If the load carrying capacity is governed by the yielding of the bolt, the gable frame structure with the rigid beam-column joint overestimates the load bearing capacity by 17% to 25%.

  14. Investigation at transonic speeds of the lateral-control and hinge-moment characteristics of a flap-type spoiler aileron on a 60 degree delta wing

    Science.gov (United States)

    Wiley, Harleth G; Taylor, Robert T

    1954-01-01

    This paper present results of an investigation of the lateral-control and hinge-moment characteristics of a 0.67 semispan flap-type spoiler aileron on a semispan thin 60 degree delta wing at transonic speeds by the reflection-plane technique. The spoiler-aileron had a constant chord of 10.29 percent mean aerodynamic chord and was hinged at the 81.9-percent-wing-root-chord station. Tests were made with the spoiler aileron slot open, partially closed, and closed. Incremental rolling-moment coefficients were obtained through a Mach number range of 0.62 to 1.08. Results indicated reasonably linear variations of rolling-moment and hinge-moment coefficients with spoiler projection except at spoiler projections of less than -2 percent mean aerodynamic chord and angles of attack greater than 12 degrees with results generally independent of slot geometry.

  15. The intrinsically disordered domain of the antitoxin Phd chaperones the toxin Doc against irreversible inactivation and misfolding.

    Science.gov (United States)

    De Gieter, Steven; Konijnenberg, Albert; Talavera, Ariel; Butterer, Annika; Haesaerts, Sarah; De Greve, Henri; Sobott, Frank; Loris, Remy; Garcia-Pino, Abel

    2014-12-05

    The toxin Doc from the phd/doc toxin-antitoxin module targets the cellular translation machinery and is inhibited by its antitoxin partner Phd. Here we show that Phd also functions as a chaperone, keeping Doc in an active, correctly folded conformation. In the absence of Phd, Doc exists in a relatively expanded state that is prone to dimerization through domain swapping with its active site loop acting as hinge region. The domain-swapped dimer is not capable of arresting protein synthesis in vitro, whereas the Doc monomer is. Upon binding to Phd, Doc becomes more compact and is secured in its monomeric state with a neutralized active site. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. Modifications of Hinge Mechanisms for the Mobile Launcher

    Science.gov (United States)

    Ganzak, Jacob D.

    2018-01-01

    The further development and modifications made towards the integration of the upper and lower hinge assemblies for the Exploration Upper Stage umbilical are presented. Investigative work is included to show the process of applying updated NASA Standards within component and assembly drawings for selected manufacturers. Component modifications with the addition of drawings are created to precisely display part geometries and geometric tolerances, along with proper methods of fabrication. Comparison of newly updated components with original Apollo era components is essential to correctly model the part characteristics and parameters, i.e. mass properties, material selection, weldments, and tolerances. 3-Dimensional modeling software is used to demonstrate the necessary improvements. In order to share and corroborate these changes, a document management system is used to store the various components and associated drawings. These efforts will contribute towards the Mobile Launcher for Exploration Mission 2 to provide proper rotation of the Exploration Upper Stage umbilical, necessary for providing cryogenic fill and drain capabilities.

  17. Using Highlighting to Train Attentional Expertise.

    Science.gov (United States)

    Roads, Brett; Mozer, Michael C; Busey, Thomas A

    2016-01-01

    Acquiring expertise in complex visual tasks is time consuming. To facilitate the efficient training of novices on where to look in these tasks, we propose an attentional highlighting paradigm. Highlighting involves dynamically modulating the saliency of a visual image to guide attention along the fixation path of a domain expert who had previously viewed the same image. In Experiment 1, we trained naive subjects via attentional highlighting on a fingerprint-matching task. Before and after training, we asked subjects to freely inspect images containing pairs of prints and determine whether the prints matched. Fixation sequences were automatically scored for the degree of expertise exhibited using a Bayesian discriminative model of novice and expert gaze behavior. Highlighted training causes gaze behavior to become more expert-like not only on the trained images but also on transfer images, indicating generalization of learning. In Experiment 2, to control for the possibility that the increase in expertise is due to mere exposure, we trained subjects via highlighting of fixation sequences from novices, not experts, and observed no transition toward expertise. In Experiment 3, to determine the specificity of the training effect, we trained subjects with expert fixation sequences from images other than the one being viewed, which preserves coarse-scale statistics of expert gaze but provides no information about fine-grain features. Observing at least a partial transition toward expertise, we obtain only weak evidence that the highlighting procedure facilitates the learning of critical local features. We discuss possible improvements to the highlighting procedure.

  18. Using Highlighting to Train Attentional Expertise.

    Directory of Open Access Journals (Sweden)

    Brett Roads

    Full Text Available Acquiring expertise in complex visual tasks is time consuming. To facilitate the efficient training of novices on where to look in these tasks, we propose an attentional highlighting paradigm. Highlighting involves dynamically modulating the saliency of a visual image to guide attention along the fixation path of a domain expert who had previously viewed the same image. In Experiment 1, we trained naive subjects via attentional highlighting on a fingerprint-matching task. Before and after training, we asked subjects to freely inspect images containing pairs of prints and determine whether the prints matched. Fixation sequences were automatically scored for the degree of expertise exhibited using a Bayesian discriminative model of novice and expert gaze behavior. Highlighted training causes gaze behavior to become more expert-like not only on the trained images but also on transfer images, indicating generalization of learning. In Experiment 2, to control for the possibility that the increase in expertise is due to mere exposure, we trained subjects via highlighting of fixation sequences from novices, not experts, and observed no transition toward expertise. In Experiment 3, to determine the specificity of the training effect, we trained subjects with expert fixation sequences from images other than the one being viewed, which preserves coarse-scale statistics of expert gaze but provides no information about fine-grain features. Observing at least a partial transition toward expertise, we obtain only weak evidence that the highlighting procedure facilitates the learning of critical local features. We discuss possible improvements to the highlighting procedure.

  19. 3DSwap: Curated knowledgebase of proteins involved in 3D domain swapping

    KAUST Repository

    Shameer, Khader

    2011-09-29

    Three-dimensional domain swapping is a unique protein structural phenomenon where two or more protein chains in a protein oligomer share a common structural segment between individual chains. This phenomenon is observed in an array of protein structures in oligomeric conformation. Protein structures in swapped conformations perform diverse functional roles and are also associated with deposition diseases in humans. We have performed in-depth literature curation and structural bioinformatics analyses to develop an integrated knowledgebase of proteins involved in 3D domain swapping. The hallmark of 3D domain swapping is the presence of distinct structural segments such as the hinge and swapped regions. We have curated the literature to delineate the boundaries of these regions. In addition, we have defined several new concepts like \\'secondary major interface\\' to represent the interface properties arising as a result of 3D domain swapping, and a new quantitative measure for the \\'extent of swapping\\' in structures. The catalog of proteins reported in 3DSwap knowledgebase has been generated using an integrated structural bioinformatics workflow of database searches, literature curation, by structure visualization and sequence-structure-function analyses. The current version of the 3DSwap knowledgebase reports 293 protein structures, the analysis of such a compendium of protein structures will further the understanding molecular factors driving 3D domain swapping. The Author(s) 2011.

  20. Influence of the subducting plate velocity on the geometry of the slab and migration of the subduction hinge

    NARCIS (Netherlands)

    Schellart, Wouter P.

    2005-01-01

    Geological observations indicate that along two active continental margins (East Asia and Mediterranean) major phases of overriding plate extension, resulting from subduction hinge-retreat, occurred synchronously with a reduction in subducting plate velocity. In this paper, results of fluid

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

    International Nuclear Information System (INIS)

    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. 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.

  3. Structural determination of functional units of the nucleotide binding domain (NBD94 of the reticulocyte binding protein Py235 of Plasmodium yoelii.

    Directory of Open Access Journals (Sweden)

    Ardina Grüber

    2010-02-01

    Full Text Available Invasion of the red blood cells (RBC by the merozoite of malaria parasites involves a large number of receptor ligand interactions. The reticulocyte binding protein homologue family (RH plays an important role in erythrocyte recognition as well as virulence. Recently, it has been shown that members of RH in addition to receptor binding may also have a role as ATP/ADP sensor. A 94 kDa region named Nucleotide-Binding Domain 94 (NBD94 of Plasmodium yoelii YM, representative of the putative nucleotide binding region of RH, has been demonstrated to bind ATP and ADP selectively. Binding of ATP or ADP induced nucleotide-dependent structural changes in the C-terminal hinge-region of NBD94, and directly impacted on the RBC binding ability of RH.In order to find the smallest structural unit, able to bind nucleotides, and its coupling module, the hinge region, three truncated domains of NBD94 have been generated, termed NBD94(444-547, NBD94(566-663 and NBD94(674-793, respectively. Using fluorescence correlation spectroscopy NBD94(444-547 has been identified to form the smallest nucleotide binding segment, sensitive for ATP and ADP, which became inhibited by 4-Chloro-7-nitrobenzofurazan. The shape of NBD94(444-547 in solution was calculated from small-angle X-ray scattering data, revealing an elongated molecule, comprised of two globular domains, connected by a spiral segment of about 73.1 A in length. The high quality of the constructs, forming the hinge-region, NBD94(566-663 and NBD94(674-793 enabled to determine the first crystallographic and solution structure, respectively. The crystal structure of NBD94(566-663 consists of two helices with 97.8 A and 48.6 A in length, linked by a loop. By comparison, the low resolution structure of NBD94(674-793 in solution represents a chair-like shape with three architectural segments.These structures give the first insight into how nucleotide binding impacts on the overall structure of RH and demonstrates the

  4. Active Deformation of Malawi Rift's North Basin Hinge Zone Modulated by Reactivation of Preexisting Precambrian Shear Zone Fabric

    Science.gov (United States)

    Kolawole, F.; Atekwana, E. A.; Laó-Dávila, D. A.; Abdelsalam, M. G.; Chindandali, P. R.; Salima, J.; Kalindekafe, L.

    2018-03-01

    We integrated temporal aeromagnetic data and recent earthquake data to address the long-standing question on the role of preexisting Precambrian structures in modulating strain accommodation and subsequent ruptures leading to seismic events within the East African Rift System. We used aeromagnetic data to elucidate the relationship between the locations of the 2009 Mw 6.0 Karonga, Malawi, earthquake surface ruptures and buried basement faults along the hinge zone of the half-graben comprising the North Basin of the Malawi Rift. Through the application of derivative filters and depth-to-magnetic-source modeling, we identified and constrained the trend of the Precambrian metamorphic fabrics and correlated them to the three-dimensional structure of buried basement faults. Our results reveal an unprecedented detail of the basement fabric dominated by high-frequency WNW to NW trending magnetic lineaments associated with the Precambrian Mughese Shear Zone fabric. The high-frequency magnetic lineaments are superimposed by lower frequency NNW trending magnetic lineaments associated with possible Cenozoic faults. Surface ruptures associated with the 2009 Mw 6.0 Karonga earthquake swarm aligned with one of the NNW-trending magnetic lineaments defining a normal fault that is characterized by right-stepping segments along its northern half and coalesced segments on its southern half. Fault geometries, regional kinematics, and spatial distribution of seismicity suggest that seismogenic faults reactivated the basement fabric found along the half-graben hinge zone. We suggest that focusing of strain accommodation and seismicity along the half-graben hinge zone is facilitated and modulated by the presence of the basement fabric.

  5. Defining the mechanical properties of a spring-hinged ankle foot orthosis to assess its potential use in children with spastic cerebral palsy.

    Science.gov (United States)

    Kerkum, Yvette L; Brehm, Merel-Anne; Buizer, Annemieke I; van den Noort, Josien C; Becher, Jules G; Harlaar, Jaap

    2014-12-01

    A rigid ventral shelf ankle foot orthosis (AFO) may improve gait in children with spastic cerebral palsy (SCP) whose gait is characterized by excessive knee flexion in stance. However, these AFOs can also impede ankle range of motion (ROM) and thereby inhibit push-off power. A more spring-like AFO can enhance push-off and may potentially reduce walking energy cost. The recent development of an adjustable spring-hinged AFO now allows adjustment of AFO stiffness, enabling tuning toward optimal gait performance. This study aims to quantify the mechanical properties of this spring-hinged AFO for each of its springs and settings. Using an AFO stiffness tester, two AFO hinges and their accompanying springs were measured. The springs showed a stiffness range of 0.01-1.82 N · m · deg(-1). The moment-threshold increased with increasing stiffness (1.13-12.1 N · m), while ROM decreased (4.91-16.5°). Energy was returned by all springs (11.5-116.3 J). These results suggest that the two stiffest available springs should improve joint kinematics and enhance push-off in children with SCP walking with excessive knee flexion.

  6. Genome-Wide Prediction and Analysis of 3D-Domain Swapped Proteins in the Human Genome from Sequence Information.

    Science.gov (United States)

    Upadhyay, Atul Kumar; Sowdhamini, Ramanathan

    2016-01-01

    3D-domain swapping is one of the mechanisms of protein oligomerization and the proteins exhibiting this phenomenon have many biological functions. These proteins, which undergo domain swapping, have acquired much attention owing to their involvement in human diseases, such as conformational diseases, amyloidosis, serpinopathies, proteionopathies etc. Early realisation of proteins in the whole human genome that retain tendency to domain swap will enable many aspects of disease control management. Predictive models were developed by using machine learning approaches with an average accuracy of 78% (85.6% of sensitivity, 87.5% of specificity and an MCC value of 0.72) to predict putative domain swapping in protein sequences. These models were applied to many complete genomes with special emphasis on the human genome. Nearly 44% of the protein sequences in the human genome were predicted positive for domain swapping. Enrichment analysis was performed on the positively predicted sequences from human genome for their domain distribution, disease association and functional importance based on Gene Ontology (GO). Enrichment analysis was also performed to infer a better understanding of the functional importance of these sequences. Finally, we developed hinge region prediction, in the given putative domain swapped sequence, by using important physicochemical properties of amino acids.

  7. The structure and dynamics of tandem WW domains in a negative regulator of notch signaling, Suppressor of deltex.

    Science.gov (United States)

    Fedoroff, Oleg Y; Townson, Sharon A; Golovanov, Alexander P; Baron, Martin; Avis, Johanna M

    2004-08-13

    WW domains mediate protein recognition, usually though binding to proline-rich sequences. In many proteins, WW domains occur in tandem arrays. Whether or how individual domains within such arrays cooperate to recognize biological partners is, as yet, poorly characterized. An important question is whether functional diversity of different WW domain proteins is reflected in the structural organization and ligand interaction mechanisms of their multiple domains. We have determined the solution structure and dynamics of a pair of WW domains (WW3-4) from a Drosophila Nedd4 family protein called Suppressor of deltex (Su(dx)), a regulator of Notch receptor signaling. We find that the binding of a type 1 PPPY ligand to WW3 stabilizes the structure with effects propagating to the WW4 domain, a domain that is not active for ligand binding. Both WW domains adopt the characteristic triple-stranded beta-sheet structure, and significantly, this is the first example of a WW domain structure to include a domain (WW4) lacking the second conserved Trp (replaced by Phe). The domains are connected by a flexible linker, which allows a hinge-like motion of domains that may be important for the recognition of functionally relevant targets. Our results contrast markedly with those of the only previously determined three-dimensional structure of tandem WW domains, that of the rigidly oriented WW domain pair from the RNA-splicing factor Prp40. Our data illustrate that arrays of WW domains can exhibit a variety of higher order structures and ligand interaction mechanisms.

  8. Optimization of elastic elements of a damping devices for cylindrical hinges in crane-manipulating installations of mobile machines

    Directory of Open Access Journals (Sweden)

    Lagerev I.A.

    2016-03-01

    Full Text Available The article considers the problems of designing an original damping devices worn for cylindrical hinges in crane-manipulating installations of mobile machines. These devices can significantly reduce the additional impact load on a steel structure manipulators due to the presence of increased gaps in the hinges. Formulated the general formulation of nonlinear constrained optimization of the sizes of the elastic elements of the damping devices. Considered a promising design variants of elastic elements. For circular and arc elastic elements with circular and rectangular cross-section for-mulated the problems of optimal design including criterion functions and systems of geometric, technological, stiffness and strength penalty constraints. Analysis of the impact of various operating and design parameters on the results of optimal design of elastic elements was performed. Were set to the recommended the use of the constructive types of elastic elements to generate the required stiffness of the damper devices.

  9. God of the hinge: treating LGBTQIA patients.

    Science.gov (United States)

    Boland, Annie

    2017-11-01

    This paper looks at systems of gender within the context of analysis. It explores the unique challenges of individuation faced by transsexual, transgender, gender queer, gender non-conforming, cross-dressing and intersex patients. To receive patients generously we need to learn how a binary culture produces profound and chronic trauma. These patients wrestle with being who they are whilst simultaneously receiving negative projections and feeling invisible. While often presenting with the struggles of gender conforming individuals, understanding the specifically gendered aspect of their identity is imperative. An analyst's unconscious bias may lead to iatrogenic shaming. The author argues that rigorous, humble inquiry into the analyst's transphobia can be transformative for patient, analyst, and the work itself. Analysis may, then, provide gender-variant patients with their first remembered and numinous experience of authentic connection to self. Conjuring the image of a hinge, securely placed in the neutral region of a third space, creates a transpositive analytic temenos. Invoking the spirit of the Trickster in the construction of this matrix supports the full inclusion of gender-variant patients. Nuanced attunement scaffolds mirroring and the possibility of play. Being mindful that gender is sturdy and delicate as well as mercurial and defined enriches the analyst's listening. © 2017, The Society of Analytical Psychology.

  10. A Structurally Variable Hinged Tetrahedron Framework from DNA Origami

    Directory of Open Access Journals (Sweden)

    David M. Smith

    2011-01-01

    Full Text Available Nanometer-sized polyhedral wire-frame objects hold a wide range of potential applications both as structural scaffolds as well as a basis for synthetic nanocontainers. The utilization of DNA as basic building blocks for such structures allows the exploitation of bottom-up self-assembly in order to achieve molecular programmability through the pairing of complementary bases. In this work, we report on a hollow but rigid tetrahedron framework of 75 nm strut length constructed with the DNA origami method. Flexible hinges at each of their four joints provide a means for structural variability of the object. Through the opening of gaps along the struts, four variants can be created as confirmed by both gel electrophoresis and direct imaging techniques. The intrinsic site addressability provided by this technique allows the unique targeted attachment of dye and/or linker molecules at any point on the structure's surface, which we prove through the superresolution fluorescence microscopy technique DNA PAINT.

  11. THE ESSENTIAL DYNAMICS OF THERMOLYSIN - CONFIRMATION OF THE HINGE-BENDING MOTION AND COMPARISON OF SIMULATIONS IN VACUUM AND WATER

    NARCIS (Netherlands)

    van Aalten, D.M.F.; Amadei, A; Linssen, A.B M; Eijsink, V.G.H.; Vriend, G.; Berendsen, H.J.C.

    Comparisons of the crystal structures of thermolysin and the thermolysin-like protease produced by B. cereus have recently led to the hypothesis that neutral proteases undergo a hinge-bending motion. We have investigated this hypothesis by analyzing molecular dynamics simulations of thermolysin in

  12. Synthetic study on cystinyl peptides using solution and solid phase metodology: human IgG1 hinge region

    Czech Academy of Sciences Publication Activity Database

    Niederhafner, Petr; Gut, Vladimír; Ježek, Jan; Buděšínský, Miloš; Kašička, Václav; Wünsch, Erich; Hlaváček, Jan

    2010-01-01

    Roč. 39, č. 3 (2010), s. 641-650 ISSN 0939-4451 R&D Projects: GA ČR GA203/03/1362; GA ČR GA203/07/1517 Institutional research plan: CEZ:AV0Z40550506 Keywords : hinge region * immunoglobulin * prion protein * solution synthesis * solid phase synthesis Subject RIV: CC - Organic Chemistry Impact factor: 4.106, year: 2010

  13. [Effectiveness comparison of suspension fixation plus hinged external fixator and double plate internal fixation in treatment of type C humeral intercondylar fractures].

    Science.gov (United States)

    Zhang, Jian; Lin, Xu; Zhong, Zeli; Wu, Chao; Tan, Lun

    2017-07-01

    To compare the effectiveness of suspension fixation plus hinged external fixator with double plate internal fixation in the treatment of type C humeral intercondylar fractures. Between January 2014 and April 2016, 30 patients with type C (Association for the Study of Internal Fixation, AO/ASIF) humeral intercondylar fractures were treated. Kirschner wire suspension fixation plus hinged external fixator was used in 14 cases (group A), and double plate internal fixation in 16 cases (group B). There was no significant difference in gender, age, injury cause, disease duration, injury side, and type of fracture between 2 groups ( P >0.05). There was no significant difference in operation time and hospitalization stay between 2 groups ( P >0.05). But the intraoperative blood loss in group A was significantly less than that in group B ( P internal fixation removal, the intraoperative blood loss, and VAS score at 1 day and 3 days after operation in group A were significant better than those in group B ( P external fixator and double plate internal fixation for the treatment of type C humeral intercondylar fractures have ideal outcome in elbow function. But the suspension fixation plus hinged external fixator is better than double plate internal fixation in intraoperative blood loss, postoperative VAS score, and time of internal fixation removal.

  14. Effects of aluminum hinged shoes on the structure of contracted feet in Thoroughbred yearlings

    OpenAIRE

    TANAKA, Kousuke; HIRAGA, Atsushi; TAKAHASHI, Toshiyuki; KUWANO, Atsutoshi; MORRISON, Scott Edward

    2015-01-01

    ABSTRACT We applied aluminum hinged shoes (AHSs) to the club foot-associated contracted feet of 11 Thoroughbred yearlings to examine the effects of the shoes on the shape of the hoof and third phalanx (P III). After 3 months of AHS use, the size of the affected hooves increased significantly, reaching the approximate size of the healthy contralateral hooves with respect to the maximum lateral width of the foot, the mean ratio of the bearing border width to the coronary band width, and the mea...

  15. A bridge column with superelastic NiTi SMA and replaceable rubber hinge for earthquake damage mitigation

    Science.gov (United States)

    Varela, Sebastian; ‘Saiid' Saiidi, M.

    2016-07-01

    This paper reports a unique concept for resilient bridge columns that can undergo intense earthquake loading and remain functional with minimal damage and residual drift. In this concept, the column is designed so that its components can be easily disassembled and reassembled to facilitate material recycling and component reuse. This is meant to foster sustainability of bridge systems while minimizing monetary losses from earthquakes. Self-centering and energy dissipation in the column were provided by unbonded superelastic nickel-titanium (NiTi) shape memory alloy bars placed inside a plastic hinge element made of rubber. This replaceable plastic hinge was in turn attached to a concrete-filled carbon fiber-reinforced polymer tube and a precast concrete footing that were designed to behave elastically. The proposed concept was evaluated experimentally by testing a ¼-scale column model under simulated near-fault earthquake motions on a shake table. After testing, the model was disassembled, reassembled and tested again. The seismic performance of the reassembled model was found to be comparable to that of the ‘virgin’ model. A relatively simple computational model of the column tested that was developed in OpenSees was able to match some of the key experimental response parameters.

  16. Effect of pH on the hinge region of influenza viral protein: a combined constant pH and well-tempered molecular dynamics study

    Science.gov (United States)

    Pathak, Arup Kumar

    2018-05-01

    Despite the knowledge that the influenza protein, hemagglutinin, undergoes a large conformational change at low pH during the process of fusion with the host cell, its molecular mechanism remains elusive. The present constant pH molecular dynamics (CpHMD) study identifies the residues responsible for large conformational change in acidic condition. Based on the pKa calculations, it is predicted that His-106 is much more responsible for the large conformational change than any other residues in the hinge region of hemagglutinin protein. Potential of mean force profile from well-tempered meta-dynamics (WT-MtD) simulation is also generated along the folding pathway by considering radius of gyration (R gyr) as a collective variable (CV). It is very clear from the present WT-MtD study, that the initial bending starts at that hinge region, which may trigger other conformational changes. Both the protein–protein and protein–water HB time correlation functions are monitored along the folding pathway. The protein–protein (full or hinge region) HB time correlation functions are always found to be stronger than those of the protein–water time correlation functions. The dynamical balance between protein–protein and protein–water HB interactions favors the stabilization of the folded state.

  17. Theoretical analysis of the domain-swapped dimerization of cytochrome c: An MD and 3D-RISM approach

    Science.gov (United States)

    Yoshida, Norio; Higashi, Masahiro; Motoki, Hideyoshi; Hirota, Shun

    2018-01-01

    The structural stability of a cytochrome c domain-swapped dimer compared with that of the monomer was investigated by molecular dynamics (MD) simulations and by three-dimensional reference interaction site model (3D-RISM) theory. The structural fluctuation and structural energy of cytochrome c were treated by MD simulations, and the solvation thermodynamics was treated by 3D-RISM theory. The domain-swapped dimer state is slightly less stable than the monomer state, which is consistent with experimental observations; the total free energy difference is calculated as 25 kcal mol-1. The conformational change and translational/rotational entropy change contribute to the destabilization of the dimer, whereas the hydration and vibrational entropy contribute to the stabilization. Further analyses on the residues located at the hinge loop for swapping were conducted, and the results reveal details at the molecular level of the structural and interaction changes upon dimerization.

  18. Effects of sub-domain structure on initial magnetization curve and domain size distribution of stacked media

    International Nuclear Information System (INIS)

    Sato, S.; Kumagai, S.; Sugita, R.

    2015-01-01

    In this paper, in order to confirm the sub-domain structure in stacked media demagnetized with in-plane field, initial magnetization curves and magnetic domain size distribution were investigated. Both experimental and simulation results showed that an initial magnetization curve for the medium demagnetized with in-plane field (MDI) initially rose faster than that for the medium demagnetized with perpendicular field (MDP). It is inferred that this is because the MDI has a larger number of domain walls than the MDP due to the existence of the sub-domains, resulting in an increase in the probability of domain wall motion. Dispersion of domain size for the MDI was larger than that for the MDP. This is because sub-domains are formed not only inside the domain but also at the domain boundary region, and they change the position of the domain boundary to affect the domain size. - Highlights: • An initial magnetization curve for MDI initially rose faster than that for MDP. • Dispersion of domain size for the MDI was larger than that for the MDP. • Experimental and simulation results can be explained by existence of sub-domains

  19. System Identification A Frequency Domain Approach

    CERN Document Server

    Pintelon, Rik

    2012-01-01

    System identification is a general term used to describe mathematical tools and algorithms that build dynamical models from measured data. Used for prediction, control, physical interpretation, and the designing of any electrical systems, they are vital in the fields of electrical, mechanical, civil, and chemical engineering. Focusing mainly on frequency domain techniques, System Identification: A Frequency Domain Approach, Second Edition also studies in detail the similarities and differences with the classical time domain approach. It high??lights many of the important steps in the identi

  20. Modal Characteristics of Novel Wind Turbine Rotors with Hinged Structures

    Science.gov (United States)

    Lu, Hongya; Zeng, Pan; Lei, Liping

    2018-03-01

    The vibration problems of the wind turbine rotors have drawn public attention as the size of wind turbine has increased incredibly. Although various factors may cause the vibration problems, the flexibility is a big threat among them. Therefore, ensuring the high stiffness of the rotors by adopting novel techniques becomes a necessity. The study was a further investigation of several novel designs regarding the dynamic behaviour and the influencing mechanism. The modal testing experiments were conducted on a traditional blade and an isolated blade with the hinged rods mounted close to the root. The results showed that the rod increased both the modal frequency and the damping of the blade. More studies were done on the rods’ impact on the wind turbine rotor with a numerical model, where dimensionless parameters were defined to describe the configuration of the interveined and the bisymmetrical rods. Their influences on the modal frequencies of the rotor were analyzed and discussed.

  1. Modulation of formalin-induced pain-related behaviour by clonidine and yohimbine in the Speke's hinged tortoise (Kiniskys spekii)

    DEFF Research Database (Denmark)

    Makau, C M; Towett, P K; Abelson, K S P

    2017-01-01

    The study was designed to investigate the involvement of noradrenergic and serotonergic receptor systems in the modulation of formalin-induced pain-related behaviour in the Speke's hinged tortoise. Intradermal injection of 100 μL of formalin at a dilution of 12.5% caused pain-related behaviour (h...

  2. Floating Characteristics of Rudders and Elevators in Spinning Attitudes as Determined From Hinge-Moment-Coefficient Data With Application to Personal-Owner-Type Airplanes

    National Research Council Canada - National Science Library

    Bihrle, William

    1950-01-01

    A study was made of available rudder and elevator hinge-moment-coefficient-coefficient data in order to determine the floating characteristics of various types of rudders and elevators in spinning attitudes...

  3. The dynamics of the asymmetric motion of domain walls of sandwich domain structure in a Fe-based amorphous ribbon

    Energy Technology Data Exchange (ETDEWEB)

    Zhmetko, D.N., E-mail: sergey.zhmetko@gmail.com [Department of Physics, Zaporizhzhya National University, 66 Zhukovsky Street, 69063 Zaporizhzhya (Ukraine); Zhmetko, S.D. [Department of Physics, Zaporizhzhya National University, 66 Zhukovsky Street, 69063 Zaporizhzhya (Ukraine); Troschenkov, Y.N. [Institute for Magnetism, 36-b Vernadsky Boulevard, 03142 Kyiv (Ukraine); Matsura, A.V. [Department of Physics, Zaporizhzhya National University, 66 Zhukovsky Street, 69063 Zaporizhzhya (Ukraine)

    2013-08-15

    The frequency dependence of asymmetry of the domain walls velocity relative to the middle plane of amorphous ribbon is investigated. An additional pressure of the same direction acting on each domain wall caused by dependence of eddy current damping on the coordinate of the domain wall is revealed. The microscopic mechanisms of this additional pressure are considered. - Highlights: ► Additional pressure on the domain wall, caused by inhomogeneity of its damping. ► Asymmetry of the coordinate of the nucleation of domain walls and their damping. ► Connection between the components of additional pressure and its direction. ► Interaction of domain walls with the surface defects of the amorphous ribbon.

  4. The dynamics of the asymmetric motion of domain walls of sandwich domain structure in a Fe-based amorphous ribbon

    International Nuclear Information System (INIS)

    Zhmetko, D.N.; Zhmetko, S.D.; Troschenkov, Y.N.; Matsura, A.V.

    2013-01-01

    The frequency dependence of asymmetry of the domain walls velocity relative to the middle plane of amorphous ribbon is investigated. An additional pressure of the same direction acting on each domain wall caused by dependence of eddy current damping on the coordinate of the domain wall is revealed. The microscopic mechanisms of this additional pressure are considered. - Highlights: ► Additional pressure on the domain wall, caused by inhomogeneity of its damping. ► Asymmetry of the coordinate of the nucleation of domain walls and their damping. ► Connection between the components of additional pressure and its direction. ► Interaction of domain walls with the surface defects of the amorphous ribbon

  5. Effects of permafrost thaw on carbon emissions under aerobic and anaerobic environments in the Great Hing'an Mountains, China.

    Science.gov (United States)

    Song, Changchun; Wang, Xianwei; Miao, Yuqing; Wang, Jiaoyue; Mao, Rong; Song, Yanyu

    2014-07-15

    The carbon (C) pool of permafrost peatland is very important for the global C cycle. Little is known about how permafrost thaw could influence C emissions in the Great Hing'an Mountains of China. Through aerobic and anaerobic incubation experiments, we studied the effects of permafrost thaw on CH4 and CO2 emissions. The rates of CH4 and CO2 emissions were measured at -10, 0 and 10°C. Although there were still C emissions below 0°C, rates of CH4 and CO2 emissions significantly increased with permafrost thaw under aerobic and anaerobic conditions. The C release under aerobic conditions was greater than under anaerobic conditions, suggesting that permafrost thaw and resulting soil environment change should be important influences on C emissions. However, CH4 stored in permafrost soils could affect accurate estimation of CH4 emissions from microbial degradation. Calculated Q10 values in the permafrost soils were significantly higher than values in active-layer soils under aerobic conditions. Our results highlight that permafrost soils have greater potential decomposability than soils of the active layer, and such carbon decomposition would be more responsive to the aerobic environment. © 2013 Elsevier B.V. All rights reserved.

  6. Three-dimensional micro assembly of a hinged nickel micro device by magnetic lifting and micro resistance welding

    International Nuclear Information System (INIS)

    Chang, Chun-Wei; Hsu, Wensyang

    2009-01-01

    The three-dimensional micro assembly of hinged nickel micro devices by magnetic lifting and micro resistance welding is proposed here. By an electroplating-based surface machining process, the released nickel structure with the hinge mechanism can be fabricated. Lifting of the released micro structure to different tilted angles is accomplished by controlling the positions of a magnet beneath the device. An in situ electro-thermal actuator is used here to provide the pressing force in micro resistance welding for immobilizing the tilted structure. The proposed technique is shown to immobilize micro devices at controlled angles ranging from 14° to 90° with respect to the substrate. Design parameters such as the electro-thermal actuator and welding beam width are also investigated. It is found that there is a trade-off in beam width design between large contact pressure and low thermal deformation. Different dominated effects from resistivity enhancement and contact area enlargement during the welding process are also observed in the dynamic resistance curves. Finally, a lifted and immobilized electro-thermal bent-beam actuator is shown to displace upward about 27.7 µm with 0.56 W power input to demonstrate the capability of electrical transmission at welded joints by the proposed 3D micro assembly technique

  7. A proline-hinge alters the characteristics of the amphipathic α-helical AMPs.

    Science.gov (United States)

    Lee, Jong Kook; Gopal, Ramamourthy; Park, Seong-Cheol; Ko, Hyun Sook; Kim, Yangmee; Hahm, Kyung-Soo; Park, Yoonkyung

    2013-01-01

    HP (2-20) is a 19-aa, amphipathic, α-helical peptide with antimicrobial properties that was derived from the N-terminus of Helicobacter pylori ribosomal protein L1. We previously showed that increasing the net hydrophobicity of HP (2-20) by substituting Trp for Gln(17) and Asp(19) (Anal 3) increased the peptide's antimicrobial activity. In hydrophobic medium, Anal 3 forms an amphipathic structure consisting of an N-terminal random coil region (residues 2-5) and an extended helical region (residues 6-20). To investigate the structure-activity relationship of Anal 3, we substituted Pro for Glu(9) (Anal 3-Pro) and then examined the new peptide's three-dimensional structure, antimicrobial activity and mechanism of action. Anal 3-Pro had an α-helical structure in the presence of trifluoroethanol (TFE) and sodium dodecyl sulfate (SDS). NMR spectroscopic analysis of Anal 3-Pro's tertiary structure in SDS micelles confirmed that the kink potential introduced by Pro(10) was responsible for the helix distortion. We also found that Anal 3-Pro exhibited about 4 times greater antimicrobial activity than Anal 3. Fluorescence activated flow cytometry and confocal fluorescence microscopy showed that incorporating a Pro-hinge into Anal 3 markedly reduced its membrane permeability so that it accumulated in the cytoplasm without remaining in the cell membrane. To investigate the translocation mechanism, we assessed its ability to release of FITC-dextran. The result showed Anal 3-Pro created a pore Candida albicans revealed that Anal 3-Pro and buforin II exert similar effects on cell membranes, whereas magainin 2 exerts a different, more damaging, effect. In addition, Anal 3-Pro assumed a helix-hinge-helix structure in the presence of biological membranes and formed micropores in both bacterial and fungal membranes, through which it entered the cytoplasm and tightly bound to DNA. These results indicate that the bending region of Anal 3- Pro peptide is prerequisite for effective

  8. Normal-Force and Hinge-Moment Characteristics at Transonic Speeds of Flap-Type Ailerons at Three Spanwise Locations on a 4-Percent-Thick Sweptback-Wing-Body Model and Pressure-Distribution Measurements on an Inboard Aileron

    Science.gov (United States)

    Runckel, Jack F.; Hieser, Gerald

    1961-01-01

    An investigation has been conducted at the Langley 16-foot transonic tunnel to determine the loading characteristics of flap-type ailerons located at inboard, midspan, and outboard positions on a 45 deg. sweptback-wing-body combination. Aileron normal-force and hinge-moment data have been obtained at Mach numbers from 0.80 t o 1.03, at angles of attack up to about 27 deg., and at aileron deflections between approximately -15 deg. and 15 deg. Results of the investigation indicate that the loading over the ailerons was established by the wing-flow characteristics, and the loading shapes were irregular in the transonic speed range. The spanwise location of the aileron had little effect on the values of the slope of the curves of hinge-moment coefficient against aileron deflection, but the inboard aileron had the greatest value of the slope of the curves of hinge-moment coefficient against angle of attack and the outboard aileron had the least. Hinge-moment and aileron normal-force data taken with strain-gage instrumentation are compared with data obtained with pressure measurements.

  9. Large Negative Linear Compressibility in InH(BDC)₂ from Framework Hinging.

    Science.gov (United States)

    Zeng, Qingxin; Wang, Kai; Zou, Bo

    2017-11-08

    Materials with negative linear compressibility (NLC) counterintuitively expand along one specific direction coupled to the volume reduction when compressed uniformly. NLC with a large value is desired for compression and materials science. However, NLC is generally smaller than -20 TPa -1 . High-pressure X-ray diffraction experiments reveal that the β-quartz-like InH(BDC) 2 generates an extreme NLC (-62.4 TPa -1 ) by framework hinging. InH(BDC) 2 is much safer and lower-cost than Au + /Ag + and CN - -containing materials that dominated the fields of large NLC. This work reconfirms that a negative thermal expansion flexible framework could likely exhibit large NLC. Moreover, a large NLC could be anticipated to arise from β-quartz-like or related frameworks composed of rigid linear ligands and flexible framework angles.

  10. Simplicity and Specificity in Language: Domain-General Biases Have Domain-Specific Effects

    Science.gov (United States)

    Culbertson, Jennifer; Kirby, Simon

    2016-01-01

    The extent to which the linguistic system—its architecture, the representations it operates on, the constraints it is subject to—is specific to language has broad implications for cognitive science and its relation to evolutionary biology. Importantly, a given property of the linguistic system can be “specific” to the domain of language in several ways. For example, if the property evolved by natural selection under the pressure of the linguistic function it serves then the property is domain-specific in the sense that its design is tailored for language. Equally though, if that property evolved to serve a different function or if that property is domain-general, it may nevertheless interact with the linguistic system in a way that is unique. This gives a second sense in which a property can be thought of as specific to language. An evolutionary approach to the language faculty might at first blush appear to favor domain-specificity in the first sense, with individual properties of the language faculty being specifically linguistic adaptations. However, we argue that interactions between learning, culture, and biological evolution mean any domain-specific adaptations that evolve will take the form of weak biases rather than hard constraints. Turning to the latter sense of domain-specificity, we highlight a very general bias, simplicity, which operates widely in cognition and yet interacts with linguistic representations in domain-specific ways. PMID:26793132

  11. Effects of aluminum hinged shoes on the structure of contracted feet in Thoroughbred yearlings.

    Science.gov (United States)

    Tanaka, Kousuke; Hiraga, Atsushi; Takahashi, Toshiyuki; Kuwano, Atsutoshi; Morrison, Scott Edward

    2015-01-01

    We applied aluminum hinged shoes (AHSs) to the club foot-associated contracted feet of 11 Thoroughbred yearlings to examine the effects of the shoes on the shape of the hoof and third phalanx (P III). After 3 months of AHS use, the size of the affected hooves increased significantly, reaching the approximate size of the healthy contralateral hooves with respect to the maximum lateral width of the foot, the mean ratio of the bearing border width to the coronary band width, and the mean ratio of the solar surface width to the articular surface width. These results suggest that the AHSs corrected the contracted feet in these yearling horses.

  12. Domain wall engineering through exchange bias

    International Nuclear Information System (INIS)

    Albisetti, E.; Petti, D.

    2016-01-01

    The control of the structure and position of magnetic domain walls is at the basis of the development of different magnetic devices and architectures. Several nanofabrication techniques have been proposed to geometrically confine and shape domain wall structures; however, a fine tuning of the position and micromagnetic configuration is hardly achieved, especially in continuous films. This work shows that, by controlling the unidirectional anisotropy of a continuous ferromagnetic film through exchange bias, domain walls whose spin arrangement is generally not favored by dipolar and exchange interactions can be created. Micromagnetic simulations reveal that the domain wall width, position and profile can be tuned by establishing an abrupt change in the direction and magnitude of the exchange bias field set in the system. - Highlights: • Micromagnetic simulations study domain walls in exchange biased thin films. • Novel domain wall configurations can be stabilized via exchange bias. • Domain walls nucleate at the boundary of regions with different exchange bias. • Domain wall width and spin profile are controlled by tuning the exchange bias.

  13. PUBLIC DOMAIN PROTECTION. USES AND REUSES OF PUBLIC DOMAIN WORKS

    Directory of Open Access Journals (Sweden)

    Monica Adriana LUPAȘCU

    2015-07-01

    Full Text Available This study tries to highlight the necessity of an awareness of the right of access to the public domain, particularly using the example of works whose protection period has expired, as well as the ones which the law considers to be excluded from protection. Such works are used not only by large libraries from around the world, but also by rights holders, via different means of use, including incorporations into original works or adaptations. However, the reuse that follows these uses often only remains at the level of concept, as the notion of the public’s right of access to public domain works is not substantiated, nor is the notion of the correct or legal use of such works.

  14. Multi-functional hinge equipped with a magneto-rheological rotary damper for solar array deployment system

    Science.gov (United States)

    Wen, Mingfu; Yu, Miao; Fu, Jie; Wu, Zhengzhong

    2015-02-01

    This article describes the design and simulation of a novel multi-functional hinge equipped with a rotary magnetorheological damper for solar array deployment system, which is comprised of a hinge, an angular sensor, a positioning and locking mechanism and a rotary damper. In order to achieve the compact design in structure, some components were reused in different function modules. It's the first to use magnet-rheological fluid (MRF) to dissipate the energy in solar array deployment system. The main advantage in using MR rotary damper instead of a viscous fluid rotary damper is that the damping force of MR damper can be adjusted according to the external magnetic field environment excited. A mechanic model was built and the structure design was focused on the MR rotary damper, a damping force model of this damper is deduced based on hydromechanics with Bingham plastic constitutive model. A simulation of deployment motion was taken to validate the motion sequence of various components during the unfolding and locking process. It can be obtained that a constant damping coefficient can hardly balance the different performance of solar deployment system, then a simulation of the proposed deployment system equipped with rotary MR damper was carried out. According to the simulation, it can be obtained that the terminal velocity decreased by 75.81% and the deployment time decreased by 72.37% compared with a given constant damping coefficients. Therefore, the proposed new type of rotary damper can reach a compromise with different performance utilizing an on-off control strategy.

  15. Comparison of custom-moulded ankle orthosis with hinged joints and off-the-shelf ankle braces in preventing ankle sprain in lateral cutting movements.

    Science.gov (United States)

    Lee, Winson C C; Kobayashi, Toshiki; Choy, Barton T S; Leung, Aaron K L

    2012-06-01

    A custom moulded ankle orthosis with hinged joints potentially offers a better control over the subtalar joint and the ankle joint during lateral cutting movements, due to total contact design and increase in material strength. To test the above hypothesis by comparing it to three other available orthoses. Repeated measures. Eight subjects with a history of ankle sprains (Grade 2), and 11 subjects without such history performed lateral cutting movements in four test conditions: 1) non-orthotic, 2) custom-moulded ankle orthosis with hinges, 3) Sport-Stirrup, and 4) elastic ankle sleeve with plastic support. A VICON motion analysis system was used to study the motions at the ankle and subtalar joints. The custom-moulded ankle orthosis significantly lowered the inversion angle at initial contact (p = 0.006) and the peak inversion angle (p = 0.000) during lateral cutting movements in comparison to non-orthotic condition, while the other two orthoses did not. The three orthoses did not affect the plantarflexion motions, which had been suggested by previous studies to be important in shock wave attenuation. The custom-moulded ankle orthosis with hinges could better control inversion and thus expected to better prevent ankle sprain in lateral cutting movements. Custom-moulded ankle orthoses are not commonly used in preventing ankle sprains. This study raises the awareness of the use of custom-moulded ankle orthoses which are expected to better prevent ankle sprains.

  16. The length of a lantibiotic hinge region has profound influence on antimicrobial activity and host specificity

    Directory of Open Access Journals (Sweden)

    Liang eZhou

    2015-01-01

    Full Text Available Lantibiotics are ribosomally synthesized (methyllanthionine containing peptides which can efficiently inhibit the growth of Gram-positive bacteria. As lantibiotics kill bacteria efficiently and resistance to them is difficult to be obtained, they have the potential to be used in many applications, e.g. in pharmaceutical industry or food industry. Nisin can inhibit the growth of Gram-positive bacteria by binding to lipid II and by making pores in their membrane. The C-terminal part of nisin is known to play an important role during translocation over the membrane and forming pore complexes. However, as the thickness of bacterial membranes varies between different species and environmental conditions, this property could have an influence on the pore forming activity of nisin. To investigate this, the so-called hinge region of nisin (residues NMK was engineered to vary from one to six amino acid residues and specific activity against different indicators was compared. Antimicrobial activity in liquid culture assays showed that wild type nisin is most active, while truncation of the hinge region dramatically reduced the activity of the peptide. However, one or two amino acids extensions showed only slightly reduced activity against most indicator strains. Notably, some variants (+2, +1, -1, -2 exhibited higher antimicrobial activity than nisin in agar well diffusion assays against Lactococcus lactis MG1363, Listeria monocytogenes, Enterococcus faecalis VE14089, Bacillus sporothermodurans IC4 and Bacillus cereus 4153 at certain temperatures.

  17. Numerical modeling of cold room's hinged door opening and closing processes

    Science.gov (United States)

    Carneiro, R.; Gaspar, P. D.; Silva, P. D.; Domingues, L. C.

    2016-06-01

    The need of rationalize energy consumption in agrifood industry has fasten the development of methodologies to improve the thermal and energy performances of cold rooms. This paper presents a three-dimensional (3D) transient Computational Fluid Dynamics (CFD) modelling of a cold room to evaluate the air infiltration rate through hinged doors. A species transport model is used for modelling the tracer gas concentration decay technique. Numerical predictions indicate that air temperature difference between spaces affects the air infiltration. For this case study, the infiltration rate increases 0.016 m3 s-1 per K of air temperature difference. The knowledge about the evolution of air infiltration during door opening/closing times allows to draw some conclusions about its influence on the air conditions inside the cold room, as well as to suggest best practices and simple technical improvements that can minimize air infiltration, and consequently improve thermal performance and energy consumption rationalization.

  18. A proline-hinge alters the characteristics of the amphipathic α-helical AMPs.

    Directory of Open Access Journals (Sweden)

    Jong Kook Lee

    Full Text Available HP (2-20 is a 19-aa, amphipathic, α-helical peptide with antimicrobial properties that was derived from the N-terminus of Helicobacter pylori ribosomal protein L1. We previously showed that increasing the net hydrophobicity of HP (2-20 by substituting Trp for Gln(17 and Asp(19 (Anal 3 increased the peptide's antimicrobial activity. In hydrophobic medium, Anal 3 forms an amphipathic structure consisting of an N-terminal random coil region (residues 2-5 and an extended helical region (residues 6-20. To investigate the structure-activity relationship of Anal 3, we substituted Pro for Glu(9 (Anal 3-Pro and then examined the new peptide's three-dimensional structure, antimicrobial activity and mechanism of action. Anal 3-Pro had an α-helical structure in the presence of trifluoroethanol (TFE and sodium dodecyl sulfate (SDS. NMR spectroscopic analysis of Anal 3-Pro's tertiary structure in SDS micelles confirmed that the kink potential introduced by Pro(10 was responsible for the helix distortion. We also found that Anal 3-Pro exhibited about 4 times greater antimicrobial activity than Anal 3. Fluorescence activated flow cytometry and confocal fluorescence microscopy showed that incorporating a Pro-hinge into Anal 3 markedly reduced its membrane permeability so that it accumulated in the cytoplasm without remaining in the cell membrane. To investigate the translocation mechanism, we assessed its ability to release of FITC-dextran. The result showed Anal 3-Pro created a pore <1.8 nm in diameter, which is similar to buforin II. Notably, scanning electron microscopic observation of Candida albicans revealed that Anal 3-Pro and buforin II exert similar effects on cell membranes, whereas magainin 2 exerts a different, more damaging, effect. In addition, Anal 3-Pro assumed a helix-hinge-helix structure in the presence of biological membranes and formed micropores in both bacterial and fungal membranes, through which it entered the cytoplasm and tightly

  19. Modeling sports highlights using a time-series clustering framework and model interpretation

    Science.gov (United States)

    Radhakrishnan, Regunathan; Otsuka, Isao; Xiong, Ziyou; Divakaran, Ajay

    2005-01-01

    In our past work on sports highlights extraction, we have shown the utility of detecting audience reaction using an audio classification framework. The audio classes in the framework were chosen based on intuition. In this paper, we present a systematic way of identifying the key audio classes for sports highlights extraction using a time series clustering framework. We treat the low-level audio features as a time series and model the highlight segments as "unusual" events in a background of an "usual" process. The set of audio classes to characterize the sports domain is then identified by analyzing the consistent patterns in each of the clusters output from the time series clustering framework. The distribution of features from the training data so obtained for each of the key audio classes, is parameterized by a Minimum Description Length Gaussian Mixture Model (MDL-GMM). We also interpret the meaning of each of the mixture components of the MDL-GMM for the key audio class (the "highlight" class) that is correlated with highlight moments. Our results show that the "highlight" class is a mixture of audience cheering and commentator's excited speech. Furthermore, we show that the precision-recall performance for highlights extraction based on this "highlight" class is better than that of our previous approach which uses only audience cheering as the key highlight class.

  20. Modulation and Functional Role of the Orientations of the N- and P-Domains of Cu+ -Transporting ATPase along the Ion Transport Cycle.

    Science.gov (United States)

    Meng, Dan; Bruschweiler-Li, Lei; Zhang, Fengli; Brüschweiler, Rafael

    2015-08-18

    Ion transport of different P-type ATPases is regulated similarly through the interplay of multiple protein domains. In the presence of ATP, binding of a cation to the ion binding site in the transmembrane helices leads to the phosphorylation of the P-domain, allowing ion transfer across the membrane. The details of the mechanism, however, are not clear. Here, we report the modulation of the orientation between the N- and P-domains of Cu(+)-transporting ATPase along the ion transport cycle using high-resolution nuclear magnetic resonance spectroscopy in solution. On the basis of residual dipolar coupling measurements, it is found that the interdomain orientation (relative openness) of the N- and P-domains is distinctly modulated depending on the specific state of the N- and P-domains along the ion translocation cycle. The two domains' relative position in the apo state is semiopen, whereas it becomes closed upon binding of ATP to the N-domain. After phosphorylation of the P-domain and the release of ADP, the opening, however, becomes the widest among all the states. We reason such wide opening resulting from the departure of ADP prepares the N- and P-domains to accommodate the A-domain for interaction and, hence, promote ion transport and allow dephosphorylation of the P-domain. Such wide interdomain opening is abolished when an Asn to Asp mutation is introduced into the conserved DXXK motif located in the hinge region of the N- and P-domains of Cu(+)-ATPase, suggesting the indispensible role of the N- and P-interdomain orientation during ion transportation. Our results shed new light on the structural and mechanistic details of P-type ATPase function at large.

  1. Characterization of the minimum domain required for targeting budding yeast myosin II to the site of cell division

    Directory of Open Access Journals (Sweden)

    Tolliday Nicola J

    2006-06-01

    Full Text Available Abstract Background All eukaryotes with the exception of plants use an actomyosin ring to generate a constriction force at the site of cell division (cleavage furrow during mitosis and meiosis. The structure and filament forming abilities located in the C-terminal or tail region of one of the main components, myosin II, are important for localising the molecule to the contractile ring (CR during cytokinesis. However, it remains poorly understood how myosin II is recruited to the site of cell division and how this recruitment relates to myosin filament assembly. Significant conservation between species of the components involved in cytokinesis, including those of the CR, allows the use of easily genetically manipulated organisms, such as budding yeast (Saccharomyces cerevisiae, in the study of cytokinesis. Budding yeast has a single myosin II protein, named Myo1. Unlike most other class II myosins, the tail of Myo1 has an irregular coiled coil. In this report we use molecular genetics, biochemistry and live cell imaging to characterize the minimum localisation domain (MLD of budding yeast Myo1. Results We show that the MLD is a small region in the centre of the tail of Myo1 and that it is both necessary and sufficient for localisation of Myo1 to the yeast bud neck, the pre-determined site of cell division. Hydrodynamic measurements of the MLD, purified from bacteria or yeast, show that it is likely to exist as a trimer. We also examine the importance of a small region of low coiled coil forming probability within the MLD, which we call the hinge region. Removal of the hinge region prevents contraction of the CR. Using fluorescence recovery after photobleaching (FRAP, we show that GFP-tagged MLD is slightly more dynamic than the GFP-tagged full length molecule but less dynamic than the GFP-tagged Myo1 construct lacking the hinge region. Conclusion Our results define the intrinsic determinant for the localization of budding yeast myosin II and show

  2. Geometric modeling of controlled third-class hinged mechanisms with a stand in one extreme position for cyclic automatic machines

    Science.gov (United States)

    Khomchenko, V. G.; Varepo, L. G.; Glukhov, V. I.; Krivokhatko, E. A.

    2017-06-01

    The geometric model for the synthesis of third-class lever mechanisms is proposed, which allows, by changing the length of the auxiliary link and the position of its fixed hinge, to rearrange the movement of the working organ onto the cyclograms with different predetermined dwell times. It is noted that with the help of the proposed model, at the expense of the corresponding geometric constructions, the best uniform Chebyshev approximation can be achieved at the interval of the standstill.

  3. Inhibition of RM-1 prostate carcinoma and eliciting robust immune responses in the mouse model by using VEGF-M2-GnRH3-hinge-MVP vaccine.

    Science.gov (United States)

    Wang, Yiqin; Alahdal, Murad; Ye, Jia; Jing, Liangliang; Liu, Xiaoxin; Chen, Huan; Jin, Liang; Cao, Rongyue

    2018-01-23

    GnRH and VEGF have been investigated as prostate carcinoma enhancers that support tumor spread and progression. Although both have documented roles in prostate carcinoma and many cancer types, the weak immunogenicity of these peptides has remained a major challenge for use in immunotherapy. Here, we describe a novel strategy to inhibit GnRH and VEGF production and assess the effect on the immune responses against these hormones using the RM-1 prostate cancer model. We designed a novel recombinant fusion protein which combined GnRH and VEGF as a vaccine against this tumor. The newly constructed fusion protein hVEGF121-M2-GnRH3-hinge-MVP contains the human vascular endothelial growth factor (hVEGF121) and three copies of GnRH in sequential linear alignment and T helper epitope MVP as an immunogenic vaccine. The effectiveness of the vaccine in eliciting an immune response and attenuating the prostate tumor growth was evaluated. Results showed that administration of a new vaccine effectively elicited humoral and cellular immune responses. We found that, a novel fusion protein, hVEGF121-M2-GnRH3-hinge-MVP, effectively inhibited growth of RM-1 prostate model and effectively promoted immune response. In conclusion, hVEGF121-M2-GnRH3-hinge-MVP is an effective dual mechanism tumor vaccine that limits RM-1 prostate growth. This vaccine may be a promising strategy for the treatment of hormone refractory prostate malignancies.

  4. Synthesis of protected peptides from the human IgG1 hinge region on PEG support using disulfide bond synthons and alkaline or enzymatic detachment

    Czech Academy of Sciences Publication Activity Database

    Niederhafner, Petr; Šafařík, Martin; Šebestík, Jaroslav; Gut, Vladimír; Maloň, Petr; Hlaváček, Jan

    2006-01-01

    Roč. 47, č. 6 (2006), s. 1023-1025 ISSN 0040-4039 R&D Projects: GA ČR(CZ) GA203/03/1362 Institutional research plan: CEZ:AV0Z40550506 Keywords : peptide synthesis * IgG1 hinge peptide * PEG carrier Subject RIV: CC - Organic Chemistry Impact factor: 2.509, year: 2006

  5. 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.

  6. The three-hinged arch as an example of piezomechanic passive controlled structure

    Science.gov (United States)

    Pagnini, Luisa Carlotta; Piccardo, Giuseppe

    2016-09-01

    Although piezoelectric transducers are employed in a variety of fields, their application for vibration control of civil or industrial structures has not yet been fully developed, at the best of authors' knowledge. Thanks to a new generation of ever more performing piezoceramic materials and to the recent development of scientific proposals based on a very simple technology, this paper presents a step forward to engineering applications for the control of structural systems. A three-hinged arch controlled by piezoelectric stack actuators and passive RL electrical circuits is chosen as a simple structural model that may represent the starting point for a generalization to the most common typologies of civil and industrial engineering structures. Based on the concept of electromechanical analogy, the evolution equations are obtained through a consistent Lagrangian approach. A multimodal vibration suppression is guaranteed by the spectral analogy between the mechanical and electrical components. Preliminary applications related to free oscillations, with one or more actuators on each member, seem to lead to excellent performance in terms of multimodal damping and dissipated energy.

  7. Introduction: History of SH2 Domains and Their Applications.

    Science.gov (United States)

    Liu, Bernard A; Machida, Kazuya

    2017-01-01

    The Src Homology 2 (SH2) domain is the prototypical protein interaction module that lies at the heart of phosphotyrosine signaling. Since its serendipitous discovery, there has been a tremendous advancement in technologies and an array of techniques available for studying SH2 domains and phosphotyrosine signaling. In this chapter, we provide a glimpse of the history of SH2 domains and describe many of the tools and techniques that have been developed along the way and discuss future directions for SH2 domain studies. We highlight the gist of each chapter in this volume in the context of: the structural biology and phosphotyrosine binding; characterizing SH2 specificity and generating prediction models; systems biology and proteomics; SH2 domains in signal transduction; and SH2 domains in disease, diagnostics, and therapeutics. Many of the individual chapters provide an in-depth approach that will allow scientists to interrogate the function and role of SH2 domains.

  8. The Scope of Mobile Apps in Health Domain: Highlighting Applications Recommended by Known Organizations

    Directory of Open Access Journals (Sweden)

    Navideh Khodaei

    2015-08-01

    Full Text Available Background and objectives : With over one billion smartphones and 100 million tablets across the world, they can perform as a valuable tool in health care management and transform health care through using mobile applications. There are various medical apps in different areas for a variety of users and among these applications, some of them have been approved and recommended by well-known organizations. Material and Methods : This is a descriptive-comparative study. This article reviews the mobile apps in health and medical domains developed or recommended by BMJ, NHS, CDC, AMA, Georgetown University, NLM, University of Ottawa, HHS, UCSF, and NYC. Results : The results of this research are presented in terms of the organization developing or recommending the app, the applications’ scope, the usage category of the application and the apps’ users. Conclusion : It seems that the organizations envisioning transformation of their services are the ones which recognize the impact of mobile technologies in this regard, particularly mobile apps.

  9. 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.

  10. Categorization in the Affective Domain

    DEFF Research Database (Denmark)

    Sauciuc, Gabriela-Alina

    2011-01-01

    Data collected in Romance and Scandinavian languages (N=474) in a superordinate category name production task indicate that a multiple-strategy approach would be more suitable for accounting of categorization in the affective domain instead of a prototype approach as suggested by previous studies....... This paper will highlight performance aspects which appear to be consistent with such an interpretation, as well as an important layman- expert knowledge asymmetry in affective categorization....

  11. Changing domains in human capital measurement

    Directory of Open Access Journals (Sweden)

    Pharny D. Chrysler-Fox

    2014-09-01

    Research purpose: The aim of the study was to explore and describe changing domains within human capital management to be managed and measured. Motivation for the study: The motivation was to advance the understanding of changing measurement domains to aid practitioners to manage and measure the contribution of the human resource function and employees, in order to unlock and add value and ultimately contribute to the success of an organisation. Research design, approach and method: Unstructured, in-depth interview data of purposively selected cases from a selected panel of human resource practitioners specialising in human capital measurement was thematically analysed in this exploratory-descriptive investigation. Main findings: Findings suggested that seven domains should be managed and measured. These domains highlight new areas of impact and levels of management. In addition, crossdomain relationships in measurement allow for an understanding of the impact and potential value on which to capitalise. Practical/managerial implications: New domains to manage and measure focus the attention of practitioners beyond the transactional performance management paradigm to a transformational approach to influence the business strategy. Higher education institutions need to develop students’ cognitive skills to facilitate systems thinking. Contribution: This study suggests a new approach to managing and measuring the human capital function and the workforce.

  12. Solution structure of leptospiral LigA4 Big domain

    Energy Technology Data Exchange (ETDEWEB)

    Mei, Song; Zhang, Jiahai [Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026 (China); Zhang, Xuecheng [School of Life Sciences, Anhui University, Hefei, Anhui 230039 (China); Tu, Xiaoming, E-mail: xmtu@ustc.edu.cn [Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026 (China)

    2015-11-13

    Pathogenic Leptospiraspecies express immunoglobulin-like proteins which serve as adhesins to bind to the extracellular matrices of host cells. Leptospiral immunoglobulin-like protein A (LigA), a surface exposed protein containing tandem repeats of bacterial immunoglobulin-like (Big) domains, has been proved to be involved in the interaction of pathogenic Leptospira with mammalian host. In this study, the solution structure of the fourth Big domain of LigA (LigA4 Big domain) from Leptospira interrogans was solved by nuclear magnetic resonance (NMR). The structure of LigA4 Big domain displays a similar bacterial immunoglobulin-like fold compared with other Big domains, implying some common structural aspects of Big domain family. On the other hand, it displays some structural characteristics significantly different from classic Ig-like domain. Furthermore, Stains-all assay and NMR chemical shift perturbation revealed the Ca{sup 2+} binding property of LigA4 Big domain. - Highlights: • Determining the solution structure of a bacterial immunoglobulin-like domain from a surface protein of Leptospira. • The solution structure shows some structural characteristics significantly different from the classic Ig-like domains. • A potential Ca{sup 2+}-binding site was identified by strains-all and NMR chemical shift perturbation.

  13. Solution structure of leptospiral LigA4 Big domain

    International Nuclear Information System (INIS)

    Mei, Song; Zhang, Jiahai; Zhang, Xuecheng; Tu, Xiaoming

    2015-01-01

    Pathogenic Leptospiraspecies express immunoglobulin-like proteins which serve as adhesins to bind to the extracellular matrices of host cells. Leptospiral immunoglobulin-like protein A (LigA), a surface exposed protein containing tandem repeats of bacterial immunoglobulin-like (Big) domains, has been proved to be involved in the interaction of pathogenic Leptospira with mammalian host. In this study, the solution structure of the fourth Big domain of LigA (LigA4 Big domain) from Leptospira interrogans was solved by nuclear magnetic resonance (NMR). The structure of LigA4 Big domain displays a similar bacterial immunoglobulin-like fold compared with other Big domains, implying some common structural aspects of Big domain family. On the other hand, it displays some structural characteristics significantly different from classic Ig-like domain. Furthermore, Stains-all assay and NMR chemical shift perturbation revealed the Ca"2"+ binding property of LigA4 Big domain. - Highlights: • Determining the solution structure of a bacterial immunoglobulin-like domain from a surface protein of Leptospira. • The solution structure shows some structural characteristics significantly different from the classic Ig-like domains. • A potential Ca"2"+-binding site was identified by strains-all and NMR chemical shift perturbation.

  14. Dynamic fluctuations provide the basis of a conformational switch mechanism in apo cyclic AMP receptor protein.

    Directory of Open Access Journals (Sweden)

    Burcu Aykaç Fas

    Full Text Available Escherichia coli cyclic AMP Receptor Protein (CRP undergoes conformational changes with cAMP binding and allosterically promotes CRP to bind specifically to the DNA. In that, the structural and dynamic properties of apo CRP prior to cAMP binding are of interest for the comprehension of the activation mechanism. Here, the dynamics of apo CRP monomer/dimer and holo CRP dimer were studied by Molecular Dynamics (MD simulations and Gaussian Network Model (GNM. The interplay of the inter-domain hinge with the cAMP and DNA binding domains are pre-disposed in the apo state as a conformational switch in the CRP's allosteric communication mechanism. The hinge at L134-D138 displaying intra- and inter-subunit coupled fluctuations with the cAMP and DNA binding domains leads to the emergence of stronger coupled fluctuations between the two domains and describes an on state. The flexible regions at K52-E58, P154/D155 and I175 maintain the dynamic coupling of the two domains. With a shift in the inter-domain hinge position towards the N terminus, nevertheless, the latter correlations between the domains loosen and become disordered; L134-D138 dynamically interacts only with the cAMP and DNA binding domains of its own subunit, and an off state is assumed. We present a mechanistic view on how the structural dynamic units are hierarchically built for the allosteric functional mechanism; from apo CRP monomer to apo-to-holo CRP dimers.

  15. Hinged concrete covers protect pipelines. [Protection of submarine pipelines from underscouring, trawlboards, and dragging anchors

    Energy Technology Data Exchange (ETDEWEB)

    1977-09-01

    Providing effective protection for oil and gas pipelines is proving to be a difficult and expensive business, particularly in heavily used and environmentally sensitive waters such as the North Sea. The Danish Company Seditech has produced a design for ''hinged'' pipeline covers in concrete which are claimed to offer an effective solution to the problem. Model tests are currently (end of August 1977) being carried out at Trondheim, Norway, and this will be followed by a six-month feasibility study into the design of a suitable underwater installation vehicle. The aim is to produce total costs of the same order as pipe burial. The first step towards this has been achieved, as another Danish company has developed a combined vibration/pressure moulding system which allows individual cover elements to be produced in 3 to 5 min.

  16. Optimization of bottom-hinged flap-type wave energy converter for a specific wave rose

    Science.gov (United States)

    Behzad, Hamed; Panahi, Roozbeh

    2017-06-01

    In this paper, we conducted a numerical analysis on the bottom-hinged flap-type Wave Energy Convertor (WEC). The basic model, implemented through the study using ANSYS-AQWA, has been validated by a three-dimensional physical model of a pitching vertical cylinder. Then, a systematic parametric assessment has been performed on stiffness, damping, and WEC direction against an incoming wave rose, resulting in an optimized flap-type WEC for a specific spot in the Persian Gulf. Here, stiffness is tuned to have a near-resonance condition considering the wave rose, while damping is modified to capture the highest energy for each device direction. Moreover, such sets of specifications have been checked at different directions to present the best combination of stiffness, damping, and device heading. It has been shown that for a real condition, including different wave heights, periods, and directions, it is very important to implement the methodology introduced here to guarantee device performance.

  17. Combination Across Domains: An MEG Investigation into the Relationship between Mathematical, Pictorial, and Linguistic Processing

    Science.gov (United States)

    Bemis, Douglas K.; Pylkkänen, Liina

    2013-01-01

    Debates surrounding the evolution of language often hinge upon its relationship to cognition more generally and many investigations have attempted to demark the boundary between the two. Though results from these studies suggest that language may recruit domain-general mechanisms during certain types of complex processing, the domain-generality of basic combinatorial mechanisms that lie at the core of linguistic processing is still unknown. Our previous work (Bemis and Pylkkänen, 2011, 2012) used magnetoencephalography to isolate neural activity associated with the simple composition of an adjective and a noun (“red boat”) and found increased activity during this processing localized to the left anterior temporal lobe (lATL), ventro-medial prefrontal cortex (vmPFC), and left angular gyrus (lAG). The present study explores the domain-generality of these effects and their associated combinatorial mechanisms through two parallel non-linguistic combinatorial tasks designed to be as minimal and natural as the linguistic paradigm. In the first task, we used pictures of colored shapes to elicit combinatorial conceptual processing similar to that evoked by the linguistic expressions and find increased activity again localized to the vmPFC during combinatorial processing. This result suggests that a domain-general semantic combinatorial mechanism operates during basic linguistic composition, and that activity generated by its processing localizes to the vmPFC. In the second task, we recorded neural activity as subjects performed simple addition between two small numerals. Consistent with a wide array of recent results, we find no effects related to basic addition that coincide with our linguistic effects and instead find increased activity localized to the intraparietal sulcus. This result suggests that the scope of the previously identified linguistic effects is restricted to compositional operations and does not extend generally to all tasks that are merely similar

  18. Altering critical depinning current via domain wall pile-up in magnetic nanowires

    International Nuclear Information System (INIS)

    Geng, Liwei D.; Jin, Yongmei M.

    2015-01-01

    An important role of domain wall pile-up in current-driven domain wall depinning in magnetic nanowires is revealed using micromagnetic simulations. It is found that the critical current for domain wall depinning can be substantially reduced and conveniently tuned by controlling domain wall number in the pile-up at pinning site, in analogy to dislocation pile-up responsible for Hall–Petch effect in mechanical strength. Domain wall pinning and depinning at an s-shape bend is considered, and the effects of curvature and current crowding in magnetic circuit on domain wall behaviors are discussed. - Highlights: • Advance fundamental knowledge of current-driven domain wall phenomena. • Provide a novel approach to drastically reduce the critical depinning current. • Solve an outstanding problem of effective control of domain wall pinning/depinning. • Report appealing new findings of magnetic domain wall pile-up mechanism. • Overcome the limitations of materials properties for domain wall-based devices

  19. Using an Electronic Highlighter to Eliminate the Negative Effects of Pre-Existing, Inappropriate Highlighting

    Science.gov (United States)

    Gier, Vicki; Kreiner, David; Hudnell, Jason; Montoya, Jodi; Herring, Daniel

    2011-01-01

    The purpose of the present experiment was to determine whether using an active learning technique, electronic highlighting, can eliminate the negative effects of pre-existing, poor highlighting on reading comprehension. Participants read passages containing no highlighting, appropriate highlighting, or inappropriate highlighting. We hypothesized…

  20. High energy transients: The millisecond domain

    Science.gov (United States)

    Rao, A. R.

    2018-02-01

    The search for high energy transients in the millisecond domain has come to the focus in recent times due to the detection of gravitational wave events and the identification of fast radio bursts as cosmological sources. Here we highlight the sensitivity limitations in the currently operating hard X-ray telescopes and give some details of the search for millisecond events in the AstroSat CZT Imager data.

  1. Mutations of the RTEL1 Helicase in a Hoyeraal-Hreidarsson Syndrome Patient Highlight the Importance of the ARCH Domain.

    Science.gov (United States)

    Jullien, Laurent; Kannengiesser, Caroline; Kermasson, Laetitia; Cormier-Daire, Valérie; Leblanc, Thierry; Soulier, Jean; Londono-Vallejo, Arturo; de Villartay, Jean-Pierre; Callebaut, Isabelle; Revy, Patrick

    2016-05-01

    The DNA helicase RTEL1 participates in telomere maintenance and genome stability. Biallelic mutations in the RTEL1 gene account for the severe telomere biology disorder characteristic of the Hoyeraal-Hreidarsson syndrome (HH). Here, we report a HH patient (P4) carrying two novel compound heterozygous mutations in RTEL1: a premature stop codon (c.949A>T, p.Lys317*) and an intronic deletion leading to an exon skipping and an in-frame deletion of 25 amino-acids (p.Ile398_Lys422). P4's cells exhibit short and dysfunctional telomeres similarly to other RTEL1-deficient patients. 3D structure predictions indicated that the p.Ile398_Lys422 deletion affects a part of the helicase ARCH domain, which lines the pore formed with the core HD and the iron-sulfur cluster domains and is highly specific of sequences from the eukaryotic XPD family members. © 2016 WILEY PERIODICALS, INC.

  2. A test of the domain-specific acculturation strategy hypothesis.

    Science.gov (United States)

    Miller, Matthew J; Yang, Minji; Lim, Robert H; Hui, Kayi; Choi, Na-Yeun; Fan, Xiaoyan; Lin, Li-Ling; Grome, Rebekah E; Farrell, Jerome A; Blackmon, Sha'kema

    2013-01-01

    Acculturation literature has evolved over the past several decades and has highlighted the dynamic ways in which individuals negotiate experiences in multiple cultural contexts. The present study extends this literature by testing M. J. Miller and R. H. Lim's (2010) domain-specific acculturation strategy hypothesis-that individuals might use different acculturation strategies (i.e., assimilated, bicultural, separated, and marginalized strategies; J. W. Berry, 2003) across behavioral and values domains-in 3 independent cluster analyses with Asian American participants. Present findings supported the domain-specific acculturation strategy hypothesis as 67% to 72% of participants from 3 independent samples using different strategies across behavioral and values domains. Consistent with theory, a number of acculturation strategy cluster group differences emerged across generational status, acculturative stress, mental health symptoms, and attitudes toward seeking professional psychological help. Study limitations and future directions for research are discussed.

  3. Creativity as Action: Findings from Five Creative Domains

    Directory of Open Access Journals (Sweden)

    Vlad eGlaveanu

    2013-04-01

    Full Text Available The present paper outlines an action theory of creativity and substantiates this approach by investigating creative expression in five different domains. We propose an action framework for the analysis of creative acts built on the assumption that creativity is a relational, inter-subjective phenomenon. This framework, drawing extensively from the work of Dewey (1934 on art as experience, is used to derive a coding frame for the analysis of interview material. The article reports findings from the analysis of 60 interviews with recognised French creators in five creative domains: art, design, science, scriptwriting, and music. Results point to complex models of action and inter-action specific for each domain and also to interesting patterns of similarity and differences between domains. These findings highlight the fact that creative action takes place not ‘inside’ individual creators but ‘in between’ actors and their environment. Implications for the field of educational psychology are discussed.

  4. Glycogen synthase kinase 3-{beta} phosphorylates novel S/T-P-S/T domains in Notch1 intracellular domain and induces its nuclear localization

    Energy Technology Data Exchange (ETDEWEB)

    Han, Xiangzi [Department of Life Science, College of Natural Sciences, Hanyang University, Seoul 133-791 (Korea, Republic of); Department of Preventive Medicine, Yanbian University College of Medicine, Yanji (China); Ju, Ji-hyun [Department of Life Science, College of Natural Sciences, Hanyang University, Seoul 133-791 (Korea, Republic of); Shin, Incheol, E-mail: incheol@hanyang.ac.kr [Department of Life Science, College of Natural Sciences, Hanyang University, Seoul 133-791 (Korea, Republic of)

    2012-06-29

    Highlights: Black-Right-Pointing-Pointer Novel S/T-P-S/T domains were identified in NICD. Black-Right-Pointing-Pointer Phosphorylation of NICD on the S/T-P-S/T domains induced nuclear localization. Black-Right-Pointing-Pointer GSK-3{beta} phosphorylated S and T residues in NICD S/T-P-S/T domains. -- Abstract: We identified two S/T-P-S/T domains (2122-2124, 2126-2128) inducing Notch intracellular domain (NICD) nuclear localization. The GFP-NICD (1963-2145) fusion protein deletion mutant without classical NLS was localized in the nucleus like the full length GFP-NICD. However, quadruple substitution mutant (T2122A T2124A S2126A T2128A) showed increased cytoplasmic localization. GSK-3{beta} enhanced nuclear localization and transcriptional activity of WT NICD but not of quadruple substitution mutant. In vitro kinase assays revealed that GSK-3{beta} phosphorylated S and T residues in NICD S/T-P-S/T domains. These results suggest that the novel S/T-P-S/T domain, phosphorylated by GSK-3{beta} is also involved in the nuclear localization of NICD as well as classical NLS.

  5. 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.

  6. Defining structural and functional dimensions of the extracellular thyrotropin receptor region.

    Science.gov (United States)

    Kleinau, Gunnar; Mueller, Sandra; Jaeschke, Holger; Grzesik, Paul; Neumann, Susanne; Diehl, Anne; Paschke, Ralf; Krause, Gerd

    2011-06-24

    The extracellular region of the thyrotropin receptor (TSHR) can be subdivided into the leucine-rich repeat domain (LRRD) and the hinge region. Both the LRRD and the hinge region interact with thyrotropin (TSH) or autoantibodies. Structural data for the TSHR LRRD were previously determined by crystallization (amino acids Glu(30)-Thr(257), 10 repeats), but the structure of the hinge region is still undefined. Of note, the amino acid sequence (Trp(258)-Tyr(279)) following the crystallized LRRD comprises a pattern typical for leucine-rich repeats with conserved hydrophobic side chains stabilizing the repeat fold. Moreover, functional data for amino acids between the LRRD and the transmembrane domain were fragmentary. We therefore investigated systematically these TSHR regions by mutagenesis to reveal insights into their functional contribution and potential structural features. We found that mutations of conserved hydrophobic residues between Thr(257) and Tyr(279) cause TSHR misfold, which supports a structural fold of this peptide, probably as an additional leucine-rich repeat. Furthermore, we identified several new mutations of hydrophilic amino acids in the entire hinge region leading to partial TSHR inactivation, indicating that these positions are important for intramolecular signal transduction. In summary, we provide new information regarding the structural features and functionalities of extracellular TSHR regions. Based on these insights and in context with previous results, we suggest an extracellular activation mechanism that supports an intramolecular agonistic unit as a central switch for activating effects at the extracellular region toward the serpentine domain.

  7. Relative stabilities of IgG1 and IgG4 Fab domains: Influence of the light–heavy interchain disulfide bond architecture

    Science.gov (United States)

    Heads, James T; Adams, Ralph; D'Hooghe, Lena E; Page, Matt J T; Humphreys, David P; Popplewell, Andrew G; Lawson, Alastair D; Henry, Alistair J

    2012-01-01

    The stability of therapeutic antibodies is a prime pharmaceutical concern. In this work we examined thermal stability differences between human IgG1 and IgG4 Fab domains containing the same variable regions using the thermofluor assay. It was found that the IgG1 Fab domain is up to 11°C more stable than the IgG4 Fab domain containing the same variable region. We investigated the cause of this difference with the aim of developing a molecule with the enhanced stability of the IgG1 Fab and the biological properties of an IgG4 Fc. We found that replacing the seven residues, which differ between IgG1 CH1 and IgG4 CH1 domains, while retaining the native IgG1 light-heavy interchain disulfide (L–H) bond, did not affect thermal stability. Introducing the IgG1 type L–H interchain disulfide bond (DSB) into the IgG4 Fab resulted in an increase in thermal stability to levels observed in the IgG1 Fab with the same variable region. Conversely, replacement of the IgG1 L–H interchain DSB with the IgG4 type L–H interchain DSB reduced the thermal stability. We utilized the increased stability of the IgG1 Fab and designed a hybrid antibody with an IgG1 CH1 linked to an IgG4 Fc via an IgG1 hinge. This construct has the expected biophysical properties of both the IgG4 Fc and IgG1 Fab domains and may therefore be a pharmaceutically relevant format. PMID:22761163

  8. Crosstalk between the peroxisome proliferator-activated receptor γ (PPARγ) and the vitamin D receptor (VDR) in human breast cancer cells: PPARγ binds to VDR and inhibits 1α,25-dihydroxyvitamin D3 mediated transactivation

    International Nuclear Information System (INIS)

    Alimirah, Fatouma; Peng, Xinjian; Yuan, Liang; Mehta, Rajeshwari R.; Knethen, Andreas von; Choubey, Divaker; Mehta, Rajendra G.

    2012-01-01

    Heterodimerization and cross-talk between nuclear hormone receptors often occurs. For example, estrogen receptor alpha (ERα) physically binds to peroxisome proliferator-activated receptor gamma (PPARγ) and inhibits its transcriptional activity. The interaction between PPARγ and the vitamin D receptor (VDR) however, is unknown. Here, we elucidate the molecular mechanisms linking PPARγ and VDR signaling, and for the first time we show that PPARγ physically associates with VDR in human breast cancer cells. We found that overexpression of PPARγ decreased 1α,25-dihydroxyvitamin D 3 (1,25D 3 ) mediated transcriptional activity of the vitamin D target gene, CYP24A1, by 49% and the activity of VDRE-luc, a vitamin D responsive reporter, by 75% in T47D human breast cancer cells. Deletion mutation experiments illustrated that helices 1 and 4 of PPARγ's hinge and ligand binding domains, respectively, governed this suppressive function. Additionally, abrogation of PPARγ's AF2 domain attenuated its repressive action on 1,25D 3 transactivation, indicating that this domain is integral in inhibiting VDR signaling. PPARγ was also found to compete with VDR for their binding partner retinoid X receptor alpha (RXRα). Overexpression of RXRα blocked PPARγ's suppressive effect on 1,25D 3 action, enhancing VDR signaling. In conclusion, these observations uncover molecular mechanisms connecting the PPARγ and VDR pathways. -- Highlights: PPARγ's role on 1α,25-dihydroxyvitamin D 3 transcriptional activity is examined. ► PPARγ physically binds to VDR and inhibits 1α,25-dihydroxyvitamin D 3 action. ► PPARγ's hinge and ligand binding domains are important for this inhibitory effect. ► PPARγ competes with VDR for the availability of their binding partner, RXRα.

  9. Generating Sub-nanometer Displacement Using Reduction Mechanism Consisting of Torsional Leaf Spring Hinges

    Directory of Open Access Journals (Sweden)

    Fukuda Makoto

    2014-02-01

    Full Text Available Recent demand on the measurement resolution of precise positioning comes up to tens of picometers. Some distinguished researches have been performed to measure the displacement in picometer order, however, few of them can verify the measurement performance as available tools in industry. This is not only because the picometer displacement is not yet required for industrial use, but also due to the lack of standard tools to verify such precise displacement. We proposed a displacement reduction mechanism for generating precise displacement using torsional leaf spring hinges (TLSHs that consist of four leaf springs arranged radially. It has been demonstrated that a prototype of the reduction mechanism was able to provide one-nanometer displacement with 1/1000 reduction rate by a piezoelectric actuator. In order to clarify the potential of the reduction mechanism, a displacement reduction table that can be mounted on AFM stage was newly developed using TLSHs. This paper describes the design of the reduction mechanism and the sub-nanometer displacement performance of the table obtained from its dynamic and static characteristics measured by displacement sensors and from the AFM images

  10. Work domain constraints for modelling surgical performance.

    Science.gov (United States)

    Morineau, Thierry; Riffaud, Laurent; Morandi, Xavier; Villain, Jonathan; Jannin, Pierre

    2015-10-01

    Three main approaches can be identified for modelling surgical performance: a competency-based approach, a task-based approach, both largely explored in the literature, and a less known work domain-based approach. The work domain-based approach first describes the work domain properties that constrain the agent's actions and shape the performance. This paper presents a work domain-based approach for modelling performance during cervical spine surgery, based on the idea that anatomical structures delineate the surgical performance. This model was evaluated through an analysis of junior and senior surgeons' actions. Twenty-four cervical spine surgeries performed by two junior and two senior surgeons were recorded in real time by an expert surgeon. According to a work domain-based model describing an optimal progression through anatomical structures, the degree of adjustment of each surgical procedure to a statistical polynomial function was assessed. Each surgical procedure showed a significant suitability with the model and regression coefficient values around 0.9. However, the surgeries performed by senior surgeons fitted this model significantly better than those performed by junior surgeons. Analysis of the relative frequencies of actions on anatomical structures showed that some specific anatomical structures discriminate senior from junior performances. The work domain-based modelling approach can provide an overall statistical indicator of surgical performance, but in particular, it can highlight specific points of interest among anatomical structures that the surgeons dwelled on according to their level of expertise.

  11. Geoscience Education Opportunities: Partnerships to Advance TeacHing and Scholarship (GEOPATHS): A Kansas City Minority Student Recruitment Initiative

    Science.gov (United States)

    Adegoke, J. O.; Niemi, T. M.

    2009-12-01

    Geoscience Education Opportunities: Partnerships to Advance TeacHing and Scholarship (GEOPATHS) is a multi-year project funded by the National Science Foundation to address gaps in teacher preparation, improve teacher content in geosciences and help raise enrollment in the Geosciences, especially among populations that are traditionally underrepresented in the discipline. The project is a partnership between the University of Missouri Kansas City (UMKC) and the Kansas City Missouri School District (KCMSD). In this presentation we discuss strategies that we have successfully used to provide credible pathways into the discipline for minorities that have led to a significant increase in the number of underrepresented minority students who are interested in and majoring in geoscience fields at the University of Missouri-Kansas City.

  12. Tetravalent anti-CD20/CD3 bispecific antibody for the treatment of B cell lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Chia-Yen; Chen, Gregory J.; Tai, Pei-Han; Yang, Yu-Chen [Institute of Biologics, Development Center for Biotechnology, New Taipei City, Taiwan (China); Hsu, Yu-Shen, E-mail: yshsu@advagene.com.tw [Laboratory of Biopharmaceutical Research, Advagene Biopharma, Taipei, Taiwan (China); Chang, Mingi, E-mail: mingi.chang@advagene.com.tw [Laboratory of Biopharmaceutical Research, Advagene Biopharma, Taipei, Taiwan (China); Hsu, Chuan-Lung, E-mail: fabio@dcb.org.tw [Institute of Biologics, Development Center for Biotechnology, New Taipei City, Taiwan (China)

    2016-05-13

    Bispecific antibodies (bsAbs) are second generation antibodies for therapeutic application in immunotherapy. One of the major strategies of the bsAb platform is the recruitment of immune effector T cells by incorporating an anti-CD3 domain. A bispecific T-cell engager (BiTE), with one end having an affinity for CD3 and the other end with affinity for CD19, has been approved in the US and Europe for the treatment of acute lymphoblastic leukemia. However, due to their small size and lack of Fc region, these single-chain variable fragment (scFv) bsAbs have short half-lives in vivo. Additionally, poor solubility, structural instability, and low production yields have also become major challenges in the bulk production process. To overcome these challenges, we have engineered a tetravalent bsAb with bivalent binding specificity for the CD20 and CD3 antigen in an immunoglobulin G (IgG) format. The fusion of the anti-CD3 scFvs to the CD20 antibody via a linker-hinge domain (LHD) results in improved antibody stabilization and properties. Here we demonstrate this antibody's highly efficient cancer cell elimination in a dose-dependent manner in a CD20-expressing B lymphoblastoid cell line in vitro. Our data suggest the potential clinical application of this bsAb for the treatment of CD20-expressing B cell malignancies. - Highlights: • A bispecific antibody (bsAb) can increase immunotherapeutic efficacy. • A tetravalent bsAb with binding specificity for the CD20 and CD3 antigens is proposed. • A linker-hinge domain (LHD) within the bsAb results in improved antibody properties.

  13. BBG Highlights

    Data.gov (United States)

    Broadcasting Board of Governors — BBG Highlights is a monthly summary of the BBG's accomplishments and news and developments affecting the Agency's work. Now, for the first time, this monthly update...

  14. Influence of temperature on current-induced domain wall motion and its Walker breakdown

    International Nuclear Information System (INIS)

    Fan, Lvchao; Hu, Jingguo; Su, Yuanchang; Zhu, Jinrong

    2016-01-01

    The current-driven domain wall propagation along a thin ferromagnetic strip with thermal field is studied by means of micromagnetic simulations. The results show that the velocity of domain wall is almost independent of temperature until Walker breakdown happened. However the thermal field can suppress Walker breakdown and makes domain wall move faster. Further analysis indicates that the thermal field tends to keep the out-of-plane magnetic moment of the domain wall stay in high value, which can promote domain wall motion and suppress the Walker breakdown by breaking the period of domain wall transformation. - Highlights: • Influences of temperature on the displacement and the velocity of DW are shown. • The suppression of Walker breakdown by temperature is given. • The reason for suppressing Walker breakdown is analyzed. • The breaking transformation period of Walker breakdown by temperature is given.

  15. AEB highlights

    International Nuclear Information System (INIS)

    1975-01-01

    AEB HIGHLIGHTS is a half-yearly report reflecting the most important recent achievements of the various Research and Technical Divisions of the Atomic Energy Board. It appears alternately in English and Afrikaans [af

  16. AEB highlights

    International Nuclear Information System (INIS)

    1977-01-01

    AEB HIGHLIGHTS is a half yearly report reflecting the most important recent achievements of the various Research and Technical Divisions of the Atomic Energy Board. It appears alternately in English and Afrikaans [af

  17. Domain morphology controlled crystal habits in PbTiO{sub 3} nanocrystals

    Energy Technology Data Exchange (ETDEWEB)

    Dudhe, C.M., E-mail: chandraguptadudhe@gmail.com; Khambadkar, S.J.

    2015-11-05

    Various crystal habits and associated domain structures in PbTiO{sub 3} nanocrystals synthesized by a modified sol–gel method have been studied. Structural and morphological characterizations of synthesized nanoparticles have been done by X-ray diffraction (XRD) and transmission electron microscopy (TEM). It was found from the -z coordinates of O{sub 1} and O{sub 2} that the Ti–O{sub 6} octahedra were distorted slightly, favorable for the ferroelectric nature. TEM images show butterfly like, plate like, irregular sphere like and oval-shaped habits of the nanocrystals. 90° and 180° domain structures in these crystal habits were explored from their morphologies and appearance in the field of views. The mutual association between the crystal habit and the direction spontaneous polarization P{sub s} due to domain structures was explored. Domain wall energies of 90° and 180° domains were also estimated from the kinetic process of domain nucleation. - Highlights: • Various crystal habits of PbTiO{sub 3} nanoparticles were examined by TEM. • 90° and 180° domains were explored in the nanocrystal. • Crystal habits and domain structures were correlated. • Domain wall energies were estimated.

  18. Longitudinal analysis of domain-level breast cancer literacy among African-American women.

    Science.gov (United States)

    Mabiso, Athur; Williams, Karen Patricia; Todem, David; Templin, Thomas N

    2010-02-01

    Functional breast cancer literacy was assessed among African-American women and measured at the domain level over time. We used the Kin Keeper(SM) Cancer Prevention Intervention to educate 161 African-American women on three domains of breast cancer literacy: (i) cancer awareness, (ii) knowledge of breast cancer screening modalities and (iii) cancer prevention and control. A breast cancer literacy assessment was administered pre- and post-educational intervention at two time points followed by another assessment 12 months after the second intervention. Generalized estimating equations were specified to predict the probability of correctly answering questions in each domain over time. Domain-level literacy differentials exist; at baseline, women had higher test scores in the breast cancer prevention and control domain than the cancer awareness domain (odds ratio = 1.67, 95% confidence interval 1.19-2.34). After Kin Keeper(SM) Cancer Prevention Intervention, African-American women consistently improved their breast cancer literacy in all domains over the five time stages (P < 0.001) though at different rates for each domain. Differences in domain-level breast cancer literacy highlight the importance of assessing literacy at the domain level. Interventions to improve African-American women's breast cancer literacy should focus on knowledge of breast cancer screening modalities and cancer awareness domains.

  19. Mechanical performances of lead-free solder joint connections with applications in the aerospace domain

    Directory of Open Access Journals (Sweden)

    Georgiana PADURARU

    2016-03-01

    Full Text Available The paper presents some theoretical and experimental aspects regarding the tribological performances of lead-free solder joint connections, with application in the aerospace domain. In order to highlight the mechanical and tribological properties of solder joint in correlation with different pad finishes, there were made some mechanical determinations using a dedicated Share Test System. The theoretical model highlights the link between the experimental results and the influence of gravitational acceleration on the mechanical and functional integrity of the electronic assemblies that works in vibration environment. The paper novelty is provided by the interdisciplinary experiment that offers results that can be used in the mechanical, tribological, electronical and aerospace domains.

  20. The structure of gene product 6 of bacteriophage T4, the hinge-pin of the baseplate.

    Science.gov (United States)

    Aksyuk, Anastasia A; Leiman, Petr G; Shneider, Mikhail M; Mesyanzhinov, Vadim V; Rossmann, Michael G

    2009-06-10

    The baseplate of bacteriophage T4 is a multicomponent protein complex, which controls phage attachment to the host. It assembles from six wedges and a central hub. During infection the baseplate undergoes a large conformational change from a dome-shaped to a flat, star-shaped structure. We report the crystal structure of the C-terminal half of gene product (gp) 6 and investigate its motion with respect to the other proteins during the baseplate rearrangement. Six gp6 dimers interdigitate, forming a ring that maintains the integrity of the baseplate in both conformations. One baseplate wedge contains an N-terminal dimer of gp6, whereas neighboring wedges are tied together through the C-terminal dimer of gp6. The dimeric interactions are preserved throughout the rearrangement of the baseplate. However, the hinge angle between the N- and C-terminal parts of gp6 changes by approximately 15 degrees , accounting for a 10 A radial increase in the diameter of the gp6 ring.

  1. Constricted nanowire with stabilized magnetic domain wall

    International Nuclear Information System (INIS)

    Sbiaa, R.; Al Bahri, M.

    2016-01-01

    Domain wall (DW)-based magnetic memory offers the possibility for increasing the storage capacity. However, stability of DW remains the major drawback of this scheme. In this letter, we propose a stepped nanowire for pinning DW in a desirable position. From micromagnetic simulation, the proposed design applied to in-plane magnetic anisotropy materials shows that by adjusting the nanowire step size and its width it is possible to stabilize DW for a desirable current density range. In contrast, only a movement of DW could be seen for conventional nanowire. An extension to a multi-stepped nanowire could be used for multi-bit per cell magnetic memory. - Highlights: • A stepped nanowire is proposed to pin domain wall in desired position. • The new structure can be made by a simple off set of two single nanowires. • The critical current for moving domain wall from one state to the other could be tuned by adjusting the geometry of the device. • The device could be used for multi-bit per cell memory by extending the steps in the device.

  2. Surgical treatment of choanal atresia with transnasal endoscopic approach with stentless single side-hinged flap technique: 5 year retrospective analysis

    Directory of Open Access Journals (Sweden)

    Carmelo Saraniti

    Full Text Available Abstract Introduction: Choanal atresia is a rare congenital malformation of the nasal cavity characterized by the complete obliteration of the posterior choanae. In 67% of cases choanal atresia is unilateral, affecting mainly (71% the right nasal cavity. In contrast to the unilateral form, bilateral choanal atresia is a life-threatening condition often associated with respiratory distress with feeding and intermittent cyanosis exacerbated by crying. Surgical treatment remains the only therapeutic option. Objective: To report our experience in the use of a transnasal endoscopic approach with stentless single side-hinged flap technique for the surgical management of choanal atresia. Methods: A 5 year retrospective analysis of surgical outcomes of 18 patients treated for choanal atresia with a transnasal technique employing a single side-hinged flap without stent placement. All subjects were assessed preoperatively with a nasal endoscopy and a Maxillofacial computed tomography scan. Results: Ten males and eight females with a mean age at the time of surgery of 20.05 ± 11.32 years, underwent surgery for choanal atresia. Fifteen subjects (83.33% had a bony while 3 (26.77% a mixed bony-membranous atretic plate. Two and sixteen cases suffered from bilateral and unilateral choanal atresia respectively. No intra- and/or early postoperative complications were observed. Between 2 and 3 months after surgery two cases (11.11% of partial restenosis were found. Only one of these presented a relapse of the nasal obstruction and was subsequently successfully repaired with a second endoscopic procedure. Conclusion: The surgical technique described follows the basic requirements of corrective surgery and allows good visualization, evaluation and treatment of the atretic plate and the posterior third of the septum, in order to create the new choanal opening. We believe that the use of a stent is not necessary, as recommended in case of other surgical techniques

  3. Size and mobility of lipid domains tuned by geometrical constraints.

    Science.gov (United States)

    Schütte, Ole M; Mey, Ingo; Enderlein, Jörg; Savić, Filip; Geil, Burkhard; Janshoff, Andreas; Steinem, Claudia

    2017-07-25

    In the plasma membrane of eukaryotic cells, proteins and lipids are organized in clusters, the latter ones often called lipid domains or "lipid rafts." Recent findings highlight the dynamic nature of such domains and the key role of membrane geometry and spatial boundaries. In this study, we used porous substrates with different pore radii to address precisely the extent of the geometric constraint, permitting us to modulate and investigate the size and mobility of lipid domains in phase-separated continuous pore-spanning membranes (PSMs). Fluorescence video microscopy revealed two types of liquid-ordered ( l o ) domains in the freestanding parts of the PSMs: ( i ) immobile domains that were attached to the pore rims and ( ii ) mobile, round-shaped l o domains within the center of the PSMs. Analysis of the diffusion of the mobile l o domains by video microscopy and particle tracking showed that the domains' mobility is slowed down by orders of magnitude compared with the unrestricted case. We attribute the reduced mobility to the geometric confinement of the PSM, because the drag force is increased substantially due to hydrodynamic effects generated by the presence of these boundaries. Our system can serve as an experimental test bed for diffusion of 2D objects in confined geometry. The impact of hydrodynamics on the mobility of enclosed lipid domains can have great implications for the formation and lateral transport of signaling platforms.

  4. Meteoric water circulation and rolling-hinge detachment faulting: Example of the Northern Snake Range core complex, Nevada

    Science.gov (United States)

    Gébelin, Aude; Teyssier, Christian; Heizler, Matthew T.; Andreas, Mulch

    2014-05-01

    The Northern Snake Range metamorphic core complex developed as a consequence of Oligo-Miocene extension of the Basin and Range Province and is bounded by an arched detachment that separates the cold, brittle upper crust from the ductile middle crust. On the western and eastern limbs of the arch, the detachment footwall displays continuous sections of muscovite-bearing quartzite and schist from which we report new microfabrics, δD values, and 40Ar/39Ar ages. Results indicate that the two limbs record distinct stages of the metamorphic and kinematic Cenozoic events, including Eocene collapse of previously overthickned crust in the west, and one main Oligo-Miocene extensional event in the east. Quartzite from the western part of the range preserves Eocene fabrics (~49-45 Ma) that developed during coaxial deformation in the presence of metamorphic fluids. In contrast, those from the east reveal a large component of non coaxial strain, Oligo-Miocene ages (27-21 Ma) and contain recrystallized muscovite grains indicating that meteoric fluids sourced at high elevation (low-δD) infiltrated the brittle-ductile transition zone during deformation. Percolation of meteoric fluids down to the mylonitic detachment footwall was made possible by the development of an east-dipping rolling-hinge detachment system that controlled the timing and location of active faulting in the brittle upper crust and therefore the pathway of fluids from the surface to the brittle-ductile transition. Oligo-Miocene upper crustal extension was accommodated by a fan-shaped fault pattern that generated shear and tension fractures and channelized surface fluids, while top-to-the-east ductile shearing and advection of hot material in the lower plate allowed the system to be progressively exhumed. As extension proceeded, brittle normal faults active in the wedge of the hanging wall gradually rotated and translated above the detachment fault where, became inactive and precluded the circulation of fluids

  5. The profile of the domain walls in amorphous glass-covered microwires

    Energy Technology Data Exchange (ETDEWEB)

    Beck, F.; Rigue, J.N. [Universidade Federal de Santa Maria, Campus Cachoeira do Sul, RS (Brazil); Carara, M., E-mail: carara@smail.ufsm.br [Departamento de Física, Universidade Federal de Santa Maria, Santa Maria, RS (Brazil)

    2017-08-01

    Highlights: • Glass-covered microwires with positive magnetostriction were studied. • The single domain wall dynamics was studied under different conditions. • We have evaluated the profile and shape of the moving domain walls. • The domain wall evolves from a bell shape to a parabolic one when a current is applied. - Abstract: We have studied the domain wall dynamics in Joule-annealed amorphous glass-covered microwires with positive magnetostriction in the presence of an electric current, in order to evaluate the profile and shape of the moving domain wall. Such microwires are known to present magnetic bi-stability when axially magnetized. The single domain wall dynamics was evaluated under different conditions, under an axially applied stress and an electric current. We have observed the well known increasing of the domain wall damping with the applied stress due to the increase in the magnetoelastic anisotropy and, when the current is applied, depending on the current intensity and direction, a modification on the axial domain wall damping. When the orthogonal motion of the domain wall is considered, we have observed that the associated velocity present a smaller dependence on the applied current intensity. It was observed a modification on both the domain wall shape and length. In a general way, the domain wall evolves from a bell shape to a parabolic shape as the current intensity is increased. The results were explained in terms of the change in the magnetic energy promoted by the additional Oersted field.

  6. Beyond cross-domain learning: Multiple-domain nonnegative matrix factorization

    KAUST Repository

    Wang, Jim Jing-Yan; Gao, Xin

    2014-01-01

    Traditional cross-domain learning methods transfer learning from a source domain to a target domain. In this paper, we propose the multiple-domain learning problem for several equally treated domains. The multiple-domain learning problem assumes that samples from different domains have different distributions, but share the same feature and class label spaces. Each domain could be a target domain, while also be a source domain for other domains. A novel multiple-domain representation method is proposed for the multiple-domain learning problem. This method is based on nonnegative matrix factorization (NMF), and tries to learn a basis matrix and coding vectors for samples, so that the domain distribution mismatch among different domains will be reduced under an extended variation of the maximum mean discrepancy (MMD) criterion. The novel algorithm - multiple-domain NMF (MDNMF) - was evaluated on two challenging multiple-domain learning problems - multiple user spam email detection and multiple-domain glioma diagnosis. The effectiveness of the proposed algorithm is experimentally verified. © 2013 Elsevier Ltd. All rights reserved.

  7. Beyond cross-domain learning: Multiple-domain nonnegative matrix factorization

    KAUST Repository

    Wang, Jim Jing-Yan

    2014-02-01

    Traditional cross-domain learning methods transfer learning from a source domain to a target domain. In this paper, we propose the multiple-domain learning problem for several equally treated domains. The multiple-domain learning problem assumes that samples from different domains have different distributions, but share the same feature and class label spaces. Each domain could be a target domain, while also be a source domain for other domains. A novel multiple-domain representation method is proposed for the multiple-domain learning problem. This method is based on nonnegative matrix factorization (NMF), and tries to learn a basis matrix and coding vectors for samples, so that the domain distribution mismatch among different domains will be reduced under an extended variation of the maximum mean discrepancy (MMD) criterion. The novel algorithm - multiple-domain NMF (MDNMF) - was evaluated on two challenging multiple-domain learning problems - multiple user spam email detection and multiple-domain glioma diagnosis. The effectiveness of the proposed algorithm is experimentally verified. © 2013 Elsevier Ltd. All rights reserved.

  8. Custom rotating hinge total knee arthroplasty in patients with poliomyelitis affected limbs.

    Science.gov (United States)

    Rahman, Jeeshan; Hanna, Sammy A; Kayani, Babar; Miles, Jonathan; Pollock, Robin C; Skinner, John A; Briggs, Timothy W; Carrington, Richard W

    2015-05-01

    Total knee arthroplasty (TKA) in limbs affected by poliomyelitis is a technically challenging procedure. These patients often demonstrate acquired articular and metaphyseal angular deformities, bone loss, narrowness of the intramedullary canals, impaired quadriceps strength, flexion contractures and ligamentous laxity producing painful hyperextension. Thus, using condylar knee designs in these patients will likely result in early failure because of instability and abnormal load distribution. The aim of this study was to assess the outcomes associated with use of the customised (SMILES) rotating-hinge knee system at our institution for TKA in poliomyelitis-affected limbs. We retrospectively reviewed the outcome of 14 TKAs using the (SMILES) prosthesis in 13 patients with limbs affected by poliomyelitis. All patients had painful unstable knees with hyperextension. There were ten females and three males with a mean age of 66 years (range 51-84) at time of surgery. Patients were followed up clinically, radiologically and functionally with the Oxford knee score (OKS). Mean follow-up was 72 months (16-156). There were no immediate or early complications. One patient fell and sustained a peri-prosthetic fracture at seven months requiring revision to a longer stem. Radiological evaluation showed satisfactory alignment with no signs of loosening in all cases. Mean OKS improved from 11.6 (4-18) to 31.5 (18-40) postoperatively (p poliomyelitis. The device compensates well for ligamentous insufficiency as well as for any associated bony deformity.

  9. Insights into Hox protein function from a large scale combinatorial analysis of protein domains.

    Directory of Open Access Journals (Sweden)

    Samir Merabet

    2011-10-01

    Full Text Available Protein function is encoded within protein sequence and protein domains. However, how protein domains cooperate within a protein to modulate overall activity and how this impacts functional diversification at the molecular and organism levels remains largely unaddressed. Focusing on three domains of the central class Drosophila Hox transcription factor AbdominalA (AbdA, we used combinatorial domain mutations and most known AbdA developmental functions as biological readouts to investigate how protein domains collectively shape protein activity. The results uncover redundancy, interactivity, and multifunctionality of protein domains as salient features underlying overall AbdA protein activity, providing means to apprehend functional diversity and accounting for the robustness of Hox-controlled developmental programs. Importantly, the results highlight context-dependency in protein domain usage and interaction, allowing major modifications in domains to be tolerated without general functional loss. The non-pleoitropic effect of domain mutation suggests that protein modification may contribute more broadly to molecular changes underlying morphological diversification during evolution, so far thought to rely largely on modification in gene cis-regulatory sequences.

  10. Time Domains of the Hypoxic Ventilatory Response and Their Molecular Basis

    Science.gov (United States)

    Pamenter, Matthew E.; Powell, Frank L.

    2016-01-01

    Ventilatory responses to hypoxia vary widely depending on the pattern and length of hypoxic exposure. Acute, prolonged, or intermittent hypoxic episodes can increase or decrease breathing for seconds to years, both during the hypoxic stimulus, and also after its removal. These myriad effects are the result of a complicated web of molecular interactions that underlie plasticity in the respiratory control reflex circuits and ultimately control the physiology of breathing in hypoxia. Since the time domains of the physiological hypoxic ventilatory response (HVR) were identified, considerable research effort has gone toward elucidating the underlying molecular mechanisms that mediate these varied responses. This research has begun to describe complicated and plastic interactions in the relay circuits between the peripheral chemoreceptors and the ventilatory control circuits within the central nervous system. Intriguingly, many of these molecular pathways seem to share key components between the different time domains, suggesting that varied physiological HVRs are the result of specific modifications to overlapping pathways. This review highlights what has been discovered regarding the cell and molecular level control of the time domains of the HVR, and highlights key areas where further research is required. Understanding the molecular control of ventilation in hypoxia has important implications for basic physiology and is emerging as an important component of several clinical fields. PMID:27347896

  11. Structural plasticity of the N-terminal capping helix of the TPR domain of kinesin light chain.

    Directory of Open Access Journals (Sweden)

    The Quyen Nguyen

    Full Text Available Kinesin1 plays a major role in neuronal transport by recruiting many different cargos through its kinesin light chain (KLC. Various structurally unrelated cargos interact with the conserved tetratricopeptide repeat (TPR domain of KLC. The N-terminal capping helix of the TPR domain exhibits an atypical sequence and structural features that may contribute to the versatility of the TPR domain to bind different cargos. We determined crystal structures of the TPR domain of both KLC1 and KLC2 encompassing the N-terminal capping helix and show that this helix exhibits two distinct and defined orientations relative to the rest of the TPR domain. Such a difference in orientation gives rise, at the N-terminal part of the groove, to the formation of one hydrophobic pocket, as well as to electrostatic variations at the groove surface. We present a comprehensive structural analysis of available KLC1/2-TPR domain structures that highlights that ligand binding into the groove can be specific of one or the other N-terminal capping helix orientations. Further, structural analysis reveals that the N-terminal capping helix is always involved in crystal packing contacts, especially in a TPR1:TPR1' contact which highlights its propensity to be a protein-protein interaction site. Together, these results underline that the structural plasticity of the N-terminal capping helix might represent a structural determinant for TPR domain structural versatility in cargo binding.

  12. Energy landscape scheme for an intuitive understanding of complex domain dynamics in ferroelectric thin films

    Science.gov (United States)

    Heon Kim, Tae; Yoon, Jong-Gul; Hyub Baek, Seung; Park, Woong-Kyu; Mo Yang, Sang; Yup Jang, Seung; Min, Taeyuun; Chung, Jin-Seok; Eom, Chang-Beom; Won Noh, Tae

    2015-07-01

    Fundamental understanding of domain dynamics in ferroic materials has been a longstanding issue because of its relevance to many systems and to the design of nanoscale domain-wall devices. Despite many theoretical and experimental studies, a full understanding of domain dynamics still remains incomplete, partly due to complex interactions between domain-walls and disorder. We report domain-shape-preserving deterministic domain-wall motion, which directly confirms microscopic return point memory, by observing domain-wall breathing motion in ferroelectric BiFeO3 thin film using stroboscopic piezoresponse force microscopy. Spatial energy landscape that provides new insights into domain dynamics is also mapped based on the breathing motion of domain walls. The evolution of complex domain structure can be understood by the process of occupying the lowest available energy states of polarization in the energy landscape which is determined by defect-induced internal fields. Our result highlights a pathway for the novel design of ferroelectric domain-wall devices through the engineering of energy landscape using defect-induced internal fields such as flexoelectric fields.

  13. Energy landscape scheme for an intuitive understanding of complex domain dynamics in ferroelectric thin films.

    Science.gov (United States)

    Kim, Tae Heon; Yoon, Jong-Gul; Baek, Seung Hyub; Park, Woong-kyu; Yang, Sang Mo; Yup Jang, Seung; Min, Taeyuun; Chung, Jin-Seok; Eom, Chang-Beom; Noh, Tae Won

    2015-07-01

    Fundamental understanding of domain dynamics in ferroic materials has been a longstanding issue because of its relevance to many systems and to the design of nanoscale domain-wall devices. Despite many theoretical and experimental studies, a full understanding of domain dynamics still remains incomplete, partly due to complex interactions between domain-walls and disorder. We report domain-shape-preserving deterministic domain-wall motion, which directly confirms microscopic return point memory, by observing domain-wall breathing motion in ferroelectric BiFeO3 thin film using stroboscopic piezoresponse force microscopy. Spatial energy landscape that provides new insights into domain dynamics is also mapped based on the breathing motion of domain walls. The evolution of complex domain structure can be understood by the process of occupying the lowest available energy states of polarization in the energy landscape which is determined by defect-induced internal fields. Our result highlights a pathway for the novel design of ferroelectric domain-wall devices through the engineering of energy landscape using defect-induced internal fields such as flexoelectric fields.

  14. Hydrological model performance and parameter estimation in the wavelet-domain

    Directory of Open Access Journals (Sweden)

    B. Schaefli

    2009-10-01

    Full Text Available This paper proposes a method for rainfall-runoff model calibration and performance analysis in the wavelet-domain by fitting the estimated wavelet-power spectrum (a representation of the time-varying frequency content of a time series of a simulated discharge series to the one of the corresponding observed time series. As discussed in this paper, calibrating hydrological models so as to reproduce the time-varying frequency content of the observed signal can lead to different results than parameter estimation in the time-domain. Therefore, wavelet-domain parameter estimation has the potential to give new insights into model performance and to reveal model structural deficiencies. We apply the proposed method to synthetic case studies and a real-world discharge modeling case study and discuss how model diagnosis can benefit from an analysis in the wavelet-domain. The results show that for the real-world case study of precipitation – runoff modeling for a high alpine catchment, the calibrated discharge simulation captures the dynamics of the observed time series better than the results obtained through calibration in the time-domain. In addition, the wavelet-domain performance assessment of this case study highlights the frequencies that are not well reproduced by the model, which gives specific indications about how to improve the model structure.

  15. Modeling of rotary movement of the articulating crane with increased gaps in the hinge joints of the links

    Directory of Open Access Journals (Sweden)

    Lagerev I.A.

    2016-06-01

    Full Text Available The article made computer simulation of dynamics of hydraulic articulating cranes with fully rotary motion for the case when the cylindrical hinges have an increased gap. Considered the use of special damping devices to reduce shock loads due to the presence of increased gaps. In previously developed software package KBCrane performed a series of calcu-lations made it possible to establish the relationship between the stiffness and damping devices the effectiveness of their use in varying the magnitude of the gap. In the case of the rotary movement of the articulating crane, a comparative analysis of work of joints of the connection node of the boom and lifting device with no gap and with high gaps. The features of the damping devices work joints and cushioning. Conclusions on positive and negative sides of the use of elastic damping devices.

  16. Technology meets research 60 years of CERN technology : selected highlights

    CERN Document Server

    Taylor, Thomas; Treille, Daniel; Wenninger, Horst

    2017-01-01

    "Big" science and advanced technology are known to cross-fertilize. This book emphasizes the interplay between particle physics and technology at CERN that has led to breakthroughs in both research and technology over the laboratory's first 60 years. The innovations, often the work of individuals or by small teams, are illustrated with highlights describing selected technologies from the domains of accelerators and detectors. The book also presents the framework and conditions prevailing at CERN that enabled spectacular advances in technology and contributed to propel the European organization into the league of leading research laboratories in the world. While the book is specifically aimed at providing information for the technically interested general public, more expert readers may also appreciate the broad variety of subjects presented. Ample references are given for those who wish to further explore a given topic.

  17. Induced motion of domain walls in multiferroics with quadratic interaction

    Energy Technology Data Exchange (ETDEWEB)

    Gerasimchuk, Victor S., E-mail: viktor.gera@gmail.com [National Technical University of Ukraine “Kyiv Polytechnic Institute”, Peremohy Avenue 37, 03056 Kiev (Ukraine); Shitov, Anatoliy A., E-mail: shitov@mail.ru [Donbass National Academy of Civil Engineering, Derzhavina Street 2, 86123 Makeevka, Donetsk Region (Ukraine)

    2013-10-15

    We theoretically study the dynamics of 180-degree domain wall of the ab-type in magnetic materials with quadratic magnetoelectric interaction in external alternating magnetic and electric fields. The features of the oscillatory and translational motions of the domain walls and stripe structures depending on the parameters of external fields and characteristics of the multiferroics are discussed. The possibility of the domain walls drift in a purely electric field is established. - Highlights: • We study DW and stripe DS in multiferroics with quadratic magnetoelectric interaction. • We build up the theory of oscillatory and translational (drift) DW and DS motion. • DW motion can be caused by crossed alternating electric and magnetic fields. • DW motion can be caused by alternating “pure” electric field. • DW drift velocity is formed by the AFM and Dzyaloshinskii interaction terms.

  18. Computational study of the Risø-B1-18 airfoil with a hinged flap providing variable trailing edge geometry

    DEFF Research Database (Denmark)

    Troldborg, Niels

    2005-01-01

    A comprehensive computational study, in both steady and unsteady flow conditions, has been carried out to investigate the aerodynamic characteristics of the Risø-B1.18 airfoil equipped with variable trailing edge geometry as produced by a hinged flap. The function of such flaps should...... on the baseline airfoil showed excellent agreement with measurements on the same airfoil with the same specified conditions. Furthermore, a more widespread comparison with an advanced potential theory code is presented. The influence of various key parameters, such as flap shape, flap size and oscillating...... frequencies, was investigated so that an optimum design can be suggested for application with wind turbine blades. It is concluded that a moderately curved flap with flap chord to airfoil curve ratio between 0.05 and 0.10 would be an optimum choice....

  19. 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...

  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. Mapping 180° polar domains using electron backscatter diffraction and dynamical scattering simulations

    Energy Technology Data Exchange (ETDEWEB)

    Burch, Matthew J.; Fancher, Chris M.; Patala, Srikanth [Department of Materials Science and Engineering, North Carolina State University, Raleigh, NC (United States); De Graef, Marc [Department of Materials Science and Engineering, Carnegie Mellon University, Pittsburg, PA (United States); Dickey, Elizabeth C. [Department of Materials Science and Engineering, North Carolina State University, Raleigh, NC (United States)

    2017-02-15

    A novel technique, which directly and nondestructively maps polar domains using electron backscatter diffraction (EBSD) is described and demonstrated. Through dynamical diffraction simulations and quantitative comparison to experimental EBSD patterns, the absolute orientation of a non-centrosymmetric crystal can be determined. With this information, the polar domains of a material can be mapped. The technique is demonstrated by mapping the non-ferroelastic, or 180°, ferroelectric domains in periodically poled LiNbO{sub 3} single crystals. Further, the authors demonstrate the possibility of mapping polarity using this technique in other polar materials system. - Highlights: • A novel technique to directly polar domains utilizing EBSD is demonstrated. • The technique relies on dynamical diffraction simulations of EBSD patterns. • The technique is demonstrated by mapping 180° domains in LiNbO{sub 3} single crystals. • Further application of this technique to other materials classes is discussed.

  2. A method for producing uniform dose distributions in the junction regions of large hinge angle electrol fields

    International Nuclear Information System (INIS)

    Zavgorodni, S.F.; Beckham, W.A.; Roos, D.E.

    1996-01-01

    The planning problems presented by abutting electron fields are well recognised. Junctioning electron fields with large hinge angle compounds the problems because of the creation of closely situated 'hot' and 'cold' spots. The technique involving a compensated superficial x-ray (SXR) field to treat the junction region between electron fields was developed and used in a particular clinical case (treatment of a squamous cell carcinoma of the forehead/scalp). The SXR beam parameters were chosen and the compensator was designed to make the SXR field complementary to the electron fields. Application of a compensated SXR field eliminated 'cold' spots in the junction region and minimised 'hot' spots to (110%). In the clinical case discusses the 'hot' spots due to the SXR field would not appear because of increased attenuation of the soft x-rays in bone. The technique proposed produces uniform dose distribution up to 3 cm deep and can be considered as an additional tool for dealing with electron fields junctioning problems. (author)

  3. Stable multi-domain spectral penalty methods for fractional partial differential equations

    Science.gov (United States)

    Xu, Qinwu; Hesthaven, Jan S.

    2014-01-01

    We propose stable multi-domain spectral penalty methods suitable for solving fractional partial differential equations with fractional derivatives of any order. First, a high order discretization is proposed to approximate fractional derivatives of any order on any given grids based on orthogonal polynomials. The approximation order is analyzed and verified through numerical examples. Based on the discrete fractional derivative, we introduce stable multi-domain spectral penalty methods for solving fractional advection and diffusion equations. The equations are discretized in each sub-domain separately and the global schemes are obtained by weakly imposed boundary and interface conditions through a penalty term. Stability of the schemes are analyzed and numerical examples based on both uniform and nonuniform grids are considered to highlight the flexibility and high accuracy of the proposed schemes.

  4. Customized Hinged Covered Metallic Stents for the Treatment of Benign Main Bronchial Stenosis.

    Science.gov (United States)

    Han, Xinwei; Al-Tariq, Quazi; Zhao, Yanle; Li, Lei; Cheng, Zhe; Wang, Huaqi; Liu, Chao; Jiao, Dechao; Wu, Gang

    2017-08-01

    To address the limitations of silicone stents, we designed a hinged self-expandable covered metallic stent. The aim of this study was to evaluate the safety and efficacy of the customized stents in clinical applications. This was a retrospective analysis. Under conscious sedation and local anesthesia, the stents were implanted or removed by interventional radiologists, with fluoroscopic guidance. Of 24 patients with benign main bronchial stenosis, stents were successfully placed in 21 (87.5%). The low-pressure balloon before dilation failed in 1 case (4.17%) of left main bronchial cicatricial stenosis. In 2 other cases (8.33%), stent placement was abandoned. Stents were successfully removed between 29 and 103 days after the procedure. After stent removal, the follow-up lasted for at least 12 months. Restenosis occurred only in 1 case (4.55%) owing to bronchial collapse 3 days after stent removal. Dyspnea occurred in another case (4.55%) at 2 months after retrieval; recurrence was confirmed using bronchoscopy, leading to a left pneumonectomy. The described procedure is safe and easy to be performed and avoids the use of intubation, bronchoscopy, and general anesthesia. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  5. Atomic resolution structure of the E. coli YajR transporter YAM domain

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Daohua [National Laboratory of Macromolecules, National Center of Protein Science-Beijing, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Beijing 100101 (China); School of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei 430074 (China); Zhao, Yan [National Laboratory of Macromolecules, National Center of Protein Science-Beijing, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Beijing 100101 (China); School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027 (China); Fan, Junping; Liu, Xuehui; Wu, Yan; Feng, Wei [National Laboratory of Macromolecules, National Center of Protein Science-Beijing, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Beijing 100101 (China); Zhang, Xuejun C., E-mail: zhangc@ibp.ac.cn [National Laboratory of Macromolecules, National Center of Protein Science-Beijing, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Beijing 100101 (China)

    2014-07-25

    Highlights: • We report the crystal structure of the YAM domain of YajR transporter at 1.07 Å. • The YAM dimerization is related to the halogen-dependent high thermal stability. • A belt of poly-pentagonal water molecules was observed in the dimer interface. - Abstract: YajR is an Escherichia coli transporter that belongs to the major facilitator superfamily. Unlike most MFS transporters, YajR contains a carboxyl terminal, cytosolic domain of 67 amino acid residues termed YAM domain. Although it is speculated that the function of this small soluble domain is to regulate the conformational change of the 12-helix transmembrane domain, its precise regulatory role remains unclear. Here, we report the crystal structure of the YAM domain at 1.07-Å resolution, along with its structure determined using nuclear magnetic resonance. Detailed analysis of the high resolution structure revealed a symmetrical dimer in which a belt of well-ordered poly-pentagonal water molecules is embedded. A mutagenesis experiment and a thermal stability assay were used to analyze the putative role of this dimerization in response to changes in halogen concentration.

  6. A three-dimensional polarization domain retrieval method from electron diffraction data

    International Nuclear Information System (INIS)

    Pennington, Robert S.; Koch, Christoph T.

    2015-01-01

    We present an algorithm for retrieving three-dimensional domains of picometer-scale shifts in atomic positions from electron diffraction data, and apply it to simulations of ferroelectric polarization in BaTiO 3 . Our algorithm successfully and correctly retrieves polarization domains in which the Ti atom positions differ by less than 3 pm (0.4% of the unit cell diagonal distance) with 5 and 10 nm depth resolution along the beam direction, and we also retrieve unit cell strain, corresponding to tetragonal-to-cubic unit cell distortions, for 10 nm domains. Experimental applicability is also discussed. - Highlights: • We show a retrieval method for ferroelectric polarization from TEM diffraction data. • Simulated strain and polarization variations along the beam direction are retrieved. • This method can be used for 3D strain and polarization mapping without specimen tilt

  7. Variability and conservation of structural domains in divide-and-conquer approaches

    Energy Technology Data Exchange (ETDEWEB)

    Wiegand, Thomas [ETH Zurich, Physical Chemistry (Switzerland); Gardiennet, Carole [CNRS, Université de Lorraine, CRM2, UMR 7036 (France); Cadalbert, Riccardo [ETH Zurich, Physical Chemistry (Switzerland); Lacabanne, Denis; Kunert, Britta; Terradot, Laurent, E-mail: laurent.terradot@ibcp.fr; Böckmann, Anja, E-mail: a.bockmann@ibcp.fr [Université de Lyon, Institut de Biologie et Chimie des Protéines, Bases Moléculaires et Structurales des Systèmes Infectieux, Labex Ecofect, UMR 5086 CNRS (France); Meier, Beat H., E-mail: beme@ethz.ch [ETH Zurich, Physical Chemistry (Switzerland)

    2016-06-15

    The use of protein building blocks for the structure determination of multidomain proteins and protein–protein complexes, also known as the “divide and conquer” approach, is an important strategy for obtaining protein structures. Atomic-resolution X-ray or NMR data of the individual domains are combined with lower-resolution electron microscopy maps or X-ray data of the full-length protein or the protein complex. Doing so, it is often assumed that the individual domain structures remain invariant in the context of the superstructure. In this work, we show the potentials and limitations of NMR to validate this approach at the example of the dodecameric DnaB helicase from Helicobacter pylori. We investigate how sequentially assigned spectra, as well as unassigned spectral fingerprints can be used to indicate the conservation of individual domains, and also to highlight conformational differences.

  8. Alpha-helical destabilization of the Bcl-2-BH4-domain peptide abolishes its ability to inhibit the IP3 receptor.

    Directory of Open Access Journals (Sweden)

    Giovanni Monaco

    Full Text Available The anti-apoptotic Bcl-2 protein is the founding member and namesake of the Bcl-2-protein family. It has recently been demonstrated that Bcl-2, apart from its anti-apoptotic role at mitochondrial membranes, can also directly interact with the inositol 1,4,5-trisphosphate receptor (IP3R, the primary Ca(2+-release channel in the endoplasmic reticulum (ER. Bcl-2 can thereby reduce pro-apoptotic IP3R-mediated Ca(2+ release from the ER. Moreover, the Bcl-2 homology domain 4 (Bcl-2-BH4 has been identified as essential and sufficient for this IP3R-mediated anti-apoptotic activity. In the present study, we investigated whether the reported inhibitory effect of a Bcl-2-BH4 peptide on the IP 3R1 was related to the distinctive α-helical conformation of the BH4 domain peptide. We therefore designed a peptide with two glycine "hinges" replacing residues I14 and V15, of the wild-type Bcl-2-BH4 domain (Bcl-2-BH4-IV/GG. By comparing the structural and functional properties of the Bcl-2-BH4-IV/GG peptide with its native counterpart, we found that the variant contained reduced α-helicity, neither bound nor inhibited the IP 3R1 channel, and in turn lost its anti-apoptotic effect. Similar results were obtained with other substitutions in Bcl-2-BH4 that destabilized the α-helix with concomitant loss of IP3R inhibition. These results provide new insights for the further development of Bcl-2-BH4-derived peptides as specific inhibitors of the IP3R with significant pharmacological implications.

  9. Phase domain structures in cylindrical magnets under conditions of a first-order magnetic phase transition

    International Nuclear Information System (INIS)

    Dzhezherya, Yu.I.; Klymuk, O.S.

    2011-01-01

    The magnetic and resonance properties of cylindrical magnets at first-order phase transition from paramagnetic to ferromagnetic state were theoretically studied. It has been shown that in the external magnetic field directed perpendicularly to the rotation axis, formation of a specific domain structure of paramagnetic and ferromagnetic layers can be energetically favorable. The parameters of cylindrical phase domains as well as their dependences on temperature, magnetic field and material characteristics have been calculated. Peculiarities of the magnetic resonance spectra appearing as a result of the phase domain formation have been considered. Dependence of the resonance field of the system of ferromagnetic domains on magnetization and temperature has been obtained. - Highlights: → Parameters of the equilibrium system of cylindrical phase domains are calculated. → The range of fields for PM and FM phases coexistence is found. → FMR field of the disk domains is found to be lower than that of the PMR field.→ The resonance field increases with the decrease of temperature lower than T || .

  10. Atmospheric Research 2011 Technical Highlights

    Science.gov (United States)

    2012-01-01

    The 2011 Technical Highlights describes the efforts of all members of Atmospheric Research. Their dedication to advancing Earth Science through conducting research, developing and running models, designing instruments, managing projects, running field campaigns, and numerous other activities, is highlighted in this report.

  11. Brookhaven highlights

    International Nuclear Information System (INIS)

    Rowe, M.S.; Belford, M.; Cohen, A.; Greenberg, D.; Seubert, L.

    1993-01-01

    This report highlights the research activities of Brookhaven National Laboratory during the period dating from October 1, 1992 through September 30, 1993. There are contributions to the report from different programs and departments within the laboratory. These include technology transfer, RHIC, Alternating Gradient Synchrotron, physics, biology, national synchrotron light source, applied science, medical science, advanced technology, chemistry, reactor physics, safety and environmental protection, instrumentation, and computing and communications

  12. Theoretical domains: a heuristic for teaching behavioral theory in HIV/STD prevention courses.

    Science.gov (United States)

    Dolcini, M Margaret; Canin, Lisa; Gandelman, Alice; Skolnik, Heidi

    2004-10-01

    The HIV/STD epidemics have broadened the need for better behavioral intervention programs and highlighted the importance of providing training in behavioral theory to frontline program practitioners. However, there is a lack of effective methods for teaching theoretical concepts to people who may not have a background in behavioral science. This article presents a solution to this challenge by introducing a new heuristic for teaching theory and for placing individual theories/models in a broader context. Using a broad framework, we identify five domains that influence behavior: risk appraisal, self-perceptions, emotions and arousal, relationships and social influence, and environmental and structural factors. Each domain is described, and a brief overview of supporting literature is provided. Following the presentation of domains, we discuss course structure and activities.

  13. Dynamics of the Peripheral Membrane Protein P2 from Human Myelin Measured by Neutron Scattering--A Comparison between Wild-Type Protein and a Hinge Mutant.

    Directory of Open Access Journals (Sweden)

    Saara Laulumaa

    Full Text Available Myelin protein P2 is a fatty acid-binding structural component of the myelin sheath in the peripheral nervous system, and its function is related to its membrane binding capacity. Here, the link between P2 protein dynamics and structure and function was studied using elastic incoherent neutron scattering (EINS. The P38G mutation, at the hinge between the β barrel and the α-helical lid, increased the lipid stacking capacity of human P2 in vitro, and the mutated protein was also functional in cultured cells. The P38G mutation did not change the overall structure of the protein. For a deeper insight into P2 structure-function relationships, information on protein dynamics in the 10 ps to 1 ns time scale was obtained using EINS. Values of mean square displacements mainly from protein H atoms were extracted for wild-type P2 and the P38G mutant and compared. Our results show that at physiological temperatures, the P38G mutant is more dynamic than the wild-type P2 protein, especially on a slow 1-ns time scale. Molecular dynamics simulations confirmed the enhanced dynamics of the mutant variant, especially within the portal region in the presence of bound fatty acid. The increased softness of the hinge mutant of human myelin P2 protein is likely related to an enhanced flexibility of the portal region of this fatty acid-binding protein, as well as to its interactions with the lipid bilayer surface requiring conformational adaptations.

  14. Laser induced local modification of magnetic domain in Co/Pt multilayer

    International Nuclear Information System (INIS)

    Talapatra, A.; Mohanty, J.

    2016-01-01

    Manipulation of magnetic system by the use of laser has drawn the attention of contemporary research. We demonstrate here the modification of magnetic domain in perpendicularly magnetized Co/Pt multilayer by using ultrashort laser pulse. The as-prepared sample shows an out-of-plane saturation magnetic field of 803.4 mT and almost zero remanence with a labyrinth-like domain pattern at room temperature. Atomistic simulation showed that interaction with femto-second laser results in demagnetization of the material in 200 fs followed by a slower recovery. As it indicates a net loss in magnetization, so magnetic force microscopy is carried out to investigate the equilibrium state after the system is relaxed. Demagnetized random domains appeared at the centre of the laser spot with having a rim at the boundary which signifies a deterministic switching with respect to the neighbouring area. Rotation of domains at the central area with the application of small transverse field (100 mT) proves the region to be magnetically weaker. Systematic 3D micromagnetic simulation has been performed to model the laser induced change by selective reduction of anisotropy which is discussed in detail. This shows shrinking of domains to a near circular pattern to minimize the magnetostatic energy. 50% reduction in anisotropy energy is observed with increasing the total energy of the system and a sharp increase in demagnetization energy also takes place simultaneously. This also satisfies the anisotropy in domain rotation with the application of transverse field. - Highlights: • Laser induced magnetization dynamics. • Local manipulation of magnetic domains. • Deterministic switching of domains with laser. • Modeling magnetic domain structure with local anisotropy distribution.

  15. Laser induced local modification of magnetic domain in Co/Pt multilayer

    Energy Technology Data Exchange (ETDEWEB)

    Talapatra, A., E-mail: ph13p1001@iith.ac.in; Mohanty, J., E-mail: jmohanty@iith.ac.in

    2016-11-15

    Manipulation of magnetic system by the use of laser has drawn the attention of contemporary research. We demonstrate here the modification of magnetic domain in perpendicularly magnetized Co/Pt multilayer by using ultrashort laser pulse. The as-prepared sample shows an out-of-plane saturation magnetic field of 803.4 mT and almost zero remanence with a labyrinth-like domain pattern at room temperature. Atomistic simulation showed that interaction with femto-second laser results in demagnetization of the material in 200 fs followed by a slower recovery. As it indicates a net loss in magnetization, so magnetic force microscopy is carried out to investigate the equilibrium state after the system is relaxed. Demagnetized random domains appeared at the centre of the laser spot with having a rim at the boundary which signifies a deterministic switching with respect to the neighbouring area. Rotation of domains at the central area with the application of small transverse field (100 mT) proves the region to be magnetically weaker. Systematic 3D micromagnetic simulation has been performed to model the laser induced change by selective reduction of anisotropy which is discussed in detail. This shows shrinking of domains to a near circular pattern to minimize the magnetostatic energy. 50% reduction in anisotropy energy is observed with increasing the total energy of the system and a sharp increase in demagnetization energy also takes place simultaneously. This also satisfies the anisotropy in domain rotation with the application of transverse field. - Highlights: • Laser induced magnetization dynamics. • Local manipulation of magnetic domains. • Deterministic switching of domains with laser. • Modeling magnetic domain structure with local anisotropy distribution.

  16. Custom-made hinged spacers in revision knee surgery for patients with infection, bone loss and instability.

    Science.gov (United States)

    Macmull, S; Bartlett, W; Miles, J; Blunn, G W; Pollock, R C; Carrington, R W J; Skinner, J A; Cannon, S R; Briggs, T W R

    2010-12-01

    Polymethyl methacrylate spacers are commonly used during staged revision knee arthroplasty for infection. In cases with extensive bone loss and ligament instability, such spacers may not preserve limb length, joint stability and motion. We report a retrospective case series of 19 consecutive patients using a custom-made cobalt chrome hinged spacer with antibiotic-loaded cement. The "SMILES spacer" was used at first-stage revision knee arthroplasty for chronic infection associated with a significant bone loss due to failed revision total knee replacement in 11 patients (58%), tumour endoprosthesis in four patients (21%), primary knee replacement in two patients (11%) and infected metalwork following fracture or osteotomy in a further two patients (11%). Mean follow-up was 38 months (range 24-70). In 12 (63%) patients, infection was eradicated, three patients (16%) had persistent infection and four (21%) developed further infection after initially successful second-stage surgery. Above knee amputation for persistent infection was performed in two patients. In this particularly difficult to treat population, the SMILES spacer two-stage technique has demonstrated encouraging results and presents an attractive alternative to arthrodesis or amputation. Copyright © 2009 Elsevier B.V. All rights reserved.

  17. The BRCT domain is a phospho-protein binding domain.

    Science.gov (United States)

    Yu, Xiaochun; Chini, Claudia Christiano Silva; He, Miao; Mer, Georges; Chen, Junjie

    2003-10-24

    The carboxyl-terminal domain (BRCT) of the Breast Cancer Gene 1 (BRCA1) protein is an evolutionarily conserved module that exists in a large number of proteins from prokaryotes to eukaryotes. Although most BRCT domain-containing proteins participate in DNA-damage checkpoint or DNA-repair pathways, or both, the function of the BRCT domain is not fully understood. We show that the BRCA1 BRCT domain directly interacts with phosphorylated BRCA1-Associated Carboxyl-terminal Helicase (BACH1). This specific interaction between BRCA1 and phosphorylated BACH1 is cell cycle regulated and is required for DNA damage-induced checkpoint control during the transition from G2 to M phase of the cell cycle. Further, we show that two other BRCT domains interact with their respective physiological partners in a phosphorylation-dependent manner. Thirteen additional BRCT domains also preferentially bind phospho-peptides rather than nonphosphorylated control peptides. These data imply that the BRCT domain is a phospho-protein binding domain involved in cell cycle control.

  18. The measles virus phosphoprotein interacts with the linker domain of STAT1

    International Nuclear Information System (INIS)

    Devaux, Patricia; Priniski, Lauren; Cattaneo, Roberto

    2013-01-01

    The measles virus (MV) phosphoprotein (P) and V proteins block the interferon (IFN) response by impeding phosphorylation of the signal transducer and activator of transcription 1 (STAT1) by the Janus kinase 1 (JAK1). We characterized how STAT1 mutants interact with P and JAK1 phosphorylation. Certain mutants of the linker, the Src-homology 2 domain (SH2), or the transactivation domain had reduced or abolished phosphorylation through JAK1 after IFN treatment. Other mutants, mainly localized in the linker, failed to interact with P as documented by the lack of interference with nuclear translocation. Thus the functional footprint of P on STAT1 localizes mainly to the linker domain; there is also some overlap with the STAT1 phosphorylation functional footprint on the SH2 domain. Based on these observations, we discuss how the MV-P might operate to inhibit the JAK/STAT pathway. - Highlights: • Residue in the linker and SH2 domains of STAT1 are important for MV-P interaction. • Residue in the linker and SH2 domains of STAT1 are important for STAT1 phosphorylation. • Residues interferring with both functions have similar location on STAT1. • The viral P and V proteins may operate in concert to inhibit the JAK/STAT pathway

  19. The measles virus phosphoprotein interacts with the linker domain of STAT1

    Energy Technology Data Exchange (ETDEWEB)

    Devaux, Patricia, E-mail: devaux.patricia@mayo.edu; Priniski, Lauren; Cattaneo, Roberto

    2013-09-15

    The measles virus (MV) phosphoprotein (P) and V proteins block the interferon (IFN) response by impeding phosphorylation of the signal transducer and activator of transcription 1 (STAT1) by the Janus kinase 1 (JAK1). We characterized how STAT1 mutants interact with P and JAK1 phosphorylation. Certain mutants of the linker, the Src-homology 2 domain (SH2), or the transactivation domain had reduced or abolished phosphorylation through JAK1 after IFN treatment. Other mutants, mainly localized in the linker, failed to interact with P as documented by the lack of interference with nuclear translocation. Thus the functional footprint of P on STAT1 localizes mainly to the linker domain; there is also some overlap with the STAT1 phosphorylation functional footprint on the SH2 domain. Based on these observations, we discuss how the MV-P might operate to inhibit the JAK/STAT pathway. - Highlights: • Residue in the linker and SH2 domains of STAT1 are important for MV-P interaction. • Residue in the linker and SH2 domains of STAT1 are important for STAT1 phosphorylation. • Residues interferring with both functions have similar location on STAT1. • The viral P and V proteins may operate in concert to inhibit the JAK/STAT pathway.

  20. Unidirectional effect in domain wall propagation observed in bistable glass-coated microwire

    Energy Technology Data Exchange (ETDEWEB)

    Onufer, J., E-mail: jozef.onufer@tuke.sk; Ziman, J., E-mail: jan.ziman@tuke.sk; Kladivová, M., E-mail: maria.kladivova@tuke.sk

    2015-12-15

    Systematic study of domain wall velocity versus applied magnetic field dependences in glass-coated amorphous Fe{sub 77.5}Si{sub 7.5}B{sub 15} wire was carried out, revealing the existence of a very interesting phenomenon. Domain wall mobility can be significantly different in cases when magnetization reversal caused by domain wall motion results in different orientation of magnetization. The magnitude and sign of this so-called unidirectional effect can change along the wire. There are also samples with weak unidirectional effect in which it is possible, in regions of higher values of applied magnetic field, to observe the highest wall velocities. It is very probable that damping of domain wall motion is responsible for this effect. As a hypothesis a mechanism based on eddy current damping of domain wall motion was proposed for interpretation of this effect. In the framework of this mechanism asymmetric and non-linear volt-ampere characteristics of the metal–glass interface might be responsible for the unidirectional effect. - Highlights: • Unidirectional effect in domain wall propagation was observed. • The magnitude and sign of the unidirectional effect can change along the wire. • A hypothesis for interpretation of the unidirectional effect is proposed.

  1. Symposium Highlights

    International Nuclear Information System (INIS)

    Owen-Whitred, K.

    2015-01-01

    Overview/Highlights: To begin, I'd like to take a moment to highlight some of the novel elements of this Symposium as compared to those that have been held in the past. For the first time ever, this Symposium was organized around five concurrent sessions, covering over 300 papers and presentations. These sessions were complemented by an active series of exhibits put on by vendors, universities, ESARDA, INMM, and Member State Support Programmes. We also had live demonstrations throughout the week on everything from software to destructive analysis to instrumentation, which provided the participants the opportunity to see recent developments that are ready for implementation. I'm sure you all had a chance to observe - and, more importantly, interact with - the electronic Poster, or ePoster format used this past week. This technology was used here for the first time ever by the IAEA, and I'm sure was a first for many of us as well. The ePoster format allowed participants to interact with the subject matter, and the subject matter experts, in a dynamic, engaging way. In addition to the novel technology used here, I have to say that having the posters strategically embedded in the sessions on the same topic, by having each poster author introduce his or her topic to the assembled group in order to lure us to the poster area during the breaks, was also a novel and highly effective technique. A final highlight I'd like to touch on in terms of the Symposium organization is the diversity of participation. This chart shows the breakdown by geographical distribution for the Symposium, in terms of participants. There are no labels, so don't try to read any, I simply wanted to demonstrate that we had great representation in terms of both the Symposium participants in general and the session chairs more specifically-and on that note, I would just mention here that 59 Member States participated in the Symposium. But what I find especially interesting and

  2. Assessment of damage domains of the High-Temperature Engineering Test Reactor (HTTR)

    International Nuclear Information System (INIS)

    Flores, Alain; Izquierdo, José María; Tuček, Kamil; Gallego, Eduardo

    2014-01-01

    Highlights: • We developed an adequate model for the identification of damage domains of the HTTR. • We analysed an anticipated operational transient, using the HTTR5+/GASTEMP code. • We simulated several transients of the same sequence. • We identified the corresponding damage domains using two methods. • We calculated exceedance frequency using the two methods. - Abstract: This paper presents an assessment analysis of damage domains of the 30 MW th prototype High-Temperature Engineering Test Reactor (HTTR) operated by the Japan Atomic Energy Agency (JAEA). For this purpose, an in-house deterministic risk assessment computational tool was developed based on the Theory of Stimulated Dynamics (TSD). To illustrate the methodology and applicability of the developed modelling approach, assessment results of a control rod (CR) withdrawal accident during subcritical conditions are presented and compared with those obtained by the JAEA

  3. 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....

  4. Inferring domain-domain interactions from protein-protein interactions with formal concept analysis.

    Directory of Open Access Journals (Sweden)

    Susan Khor

    Full Text Available Identifying reliable domain-domain interactions will increase our ability to predict novel protein-protein interactions, to unravel interactions in protein complexes, and thus gain more information about the function and behavior of genes. One of the challenges of identifying reliable domain-domain interactions is domain promiscuity. Promiscuous domains are domains that can occur in many domain architectures and are therefore found in many proteins. This becomes a problem for a method where the score of a domain-pair is the ratio between observed and expected frequencies because the protein-protein interaction network is sparse. As such, many protein-pairs will be non-interacting and domain-pairs with promiscuous domains will be penalized. This domain promiscuity challenge to the problem of inferring reliable domain-domain interactions from protein-protein interactions has been recognized, and a number of work-arounds have been proposed. This paper reports on an application of Formal Concept Analysis to this problem. It is found that the relationship between formal concepts provides a natural way for rare domains to elevate the rank of promiscuous domain-pairs and enrich highly ranked domain-pairs with reliable domain-domain interactions. This piggybacking of promiscuous domain-pairs onto less promiscuous domain-pairs is possible only with concept lattices whose attribute-labels are not reduced and is enhanced by the presence of proteins that comprise both promiscuous and rare domains.

  5. Inferring Domain-Domain Interactions from Protein-Protein Interactions with Formal Concept Analysis

    Science.gov (United States)

    Khor, Susan

    2014-01-01

    Identifying reliable domain-domain interactions will increase our ability to predict novel protein-protein interactions, to unravel interactions in protein complexes, and thus gain more information about the function and behavior of genes. One of the challenges of identifying reliable domain-domain interactions is domain promiscuity. Promiscuous domains are domains that can occur in many domain architectures and are therefore found in many proteins. This becomes a problem for a method where the score of a domain-pair is the ratio between observed and expected frequencies because the protein-protein interaction network is sparse. As such, many protein-pairs will be non-interacting and domain-pairs with promiscuous domains will be penalized. This domain promiscuity challenge to the problem of inferring reliable domain-domain interactions from protein-protein interactions has been recognized, and a number of work-arounds have been proposed. This paper reports on an application of Formal Concept Analysis to this problem. It is found that the relationship between formal concepts provides a natural way for rare domains to elevate the rank of promiscuous domain-pairs and enrich highly ranked domain-pairs with reliable domain-domain interactions. This piggybacking of promiscuous domain-pairs onto less promiscuous domain-pairs is possible only with concept lattices whose attribute-labels are not reduced and is enhanced by the presence of proteins that comprise both promiscuous and rare domains. PMID:24586450

  6. Relations with parents and identity statuses in the relational domain in emerging adults

    Directory of Open Access Journals (Sweden)

    Justyna Michałek

    2016-09-01

    Full Text Available Background Emerging adulthood is a core developmental period in which individuals can develop a meaningful identity in the relational domain (with a romantic partner. The aim of the study was to examine relationships between relations with parents and identity statuses in the relational domain in emerging adults. Participants and procedure Participants were 266 (47.30% males emerging adults (M = 22.50, SD = 1.73. They completed self-report measures of relations with parents and identity. Results More than half of the participants were in the moratorium status or were not involved in a romantic relationship (35% and 29%, respectively. Relations with parents were linked to identity statuses in the relational domain. Particularly, the perception of low autonomy given by the father was related to less mature identity statuses. Conclusions This study highlighted that transition from singleness to stable partnerships seems to be challenging. Therefore, it is important to examine correlates of identity statuses in this domain.

  7. Two-phase flow steam generator simulations on parallel computers using domain decomposition method

    International Nuclear Information System (INIS)

    Belliard, M.

    2003-01-01

    Within the framework of the Domain Decomposition Method (DDM), we present industrial steady state two-phase flow simulations of PWR Steam Generators (SG) using iteration-by-sub-domain methods: standard and Adaptive Dirichlet/Neumann methods (ADN). The averaged mixture balance equations are solved by a Fractional-Step algorithm, jointly with the Crank-Nicholson scheme and the Finite Element Method. The algorithm works with overlapping or non-overlapping sub-domains and with conforming or nonconforming meshing. Computations are run on PC networks or on massively parallel mainframe computers. A CEA code-linker and the PVM package are used (master-slave context). SG mock-up simulations, involving up to 32 sub-domains, highlight the efficiency (speed-up, scalability) and the robustness of the chosen approach. With the DDM, the computational problem size is easily increased to about 1,000,000 cells and the CPU time is significantly reduced. The difficulties related to industrial use are also discussed. (author)

  8. Editorial highlighting and highly cited papers

    Science.gov (United States)

    Antonoyiannakis, Manolis

    Editorial highlighting-the process whereby journal editors select, at the time of publication, a small subset of papers that are ostensibly of higher quality, importance or interest-is by now a widespread practice among major scientific journal publishers. Depending on the venue, and the extent to which editorial resources are invested in the process, highlighted papers appear as News & Views, Research Highlights, Perspectives, Editors' Choice, IOP Select, Editors' Summary, Spotlight on Optics, Editors' Picks, Viewpoints, Synopses, Editors' Suggestions, etc. Here, we look at the relation between highlighted papers and highly influential papers, which we define at two levels: having received enough citations to be among the (i) top few percent of their journal, and (ii) top 1% of all physics papers. Using multiple linear regression and multilevel regression modeling we examine the parameters associated with highly influential papers. We briefly comment on cause and effect relationships between citedness and highlighting of papers.

  9. Influence of domain structure induced coupling on magnetization reversal of Co/Pt/Co film with perpendicular anisotropy

    Energy Technology Data Exchange (ETDEWEB)

    Matczak, Michał [Institute of Molecular Physics, Polish Academy of Sciences, M. Smoluchowskiego 17, 60-179 Poznań (Poland); NanoBioMedical Centre, Adam Mickiewicz University, Umultowska 85, 61-614 Poznań (Poland); Schäfer, Rudolf [Leibniz Institute for Solid State and Materials Research (IFW) Dresden, Institute for Metallic Materials, PO 270116, D-01171 Dresden (Germany); Dresden University of Technology, Institute for Materials Science, D-01062 Dresden (Germany); Urbaniak, Maciej; Kuświk, Piotr; Szymański, Bogdan; Schmidt, Marek; Aleksiejew, Jacek [Institute of Molecular Physics, Polish Academy of Sciences, M. Smoluchowskiego 17, 60-179 Poznań (Poland); Stobiecki, Feliks, E-mail: Feliks.Stobiecki@ifmpan.poznan.pl [Institute of Molecular Physics, Polish Academy of Sciences, M. Smoluchowskiego 17, 60-179 Poznań (Poland); NanoBioMedical Centre, Adam Mickiewicz University, Umultowska 85, 61-614 Poznań (Poland)

    2017-01-15

    A magnetic multilayer of substrate/Pt-15 nm/Co-0.8 nm/Pt-wedge 0–7 nm/Co-0.6 nm/Pt-2 nm structure is characterized by a perpendicular anisotropy of the Co layers and by graded interlayer coupling between them. Using magnetooptical Kerr microscopy we observed a distinct influence of magnetic domains in one Co layer on the nucleation field and positions of nucleation sites of reversed domains in the second Co layer. For sufficiently strong interlayer coupling a replication of magnetic domains from the magnetically harder layer to the magnetically softer layer is observed. - Highlights: • Co/Pt-wedge/Co layered film is characterized by a gradient of interlayer coupling. • Magnetic field controls propagation of straight domain wall. • Replication of magnetic domains in multilayers with strong ferromagnetic coupling. • Coupling induced by domains influences magnetization reversal of spin valves.

  10. Time and frequency domain analyses of the Hualien Large-Scale Seismic Test

    International Nuclear Information System (INIS)

    Kabanda, John; Kwon, Oh-Sung; Kwon, Gunup

    2015-01-01

    Highlights: • Time- and frequency-domain analysis methods are verified against each other. • The two analysis methods are validated against Hualien LSST. • The nonlinear time domain (NLTD) analysis resulted in more realistic response. • The frequency domain (FD) analysis shows amplification at resonant frequencies. • The NLTD analysis requires significant modeling and computing time. - Abstract: In the nuclear industry, the equivalent-linear frequency domain analysis method has been the de facto standard procedure primarily due to the method's computational efficiency. This study explores the feasibility of applying the nonlinear time domain analysis method for the soil–structure-interaction analysis of nuclear power facilities. As a first step, the equivalency of the time and frequency domain analysis methods is verified through a site response analysis of one-dimensional soil, a dynamic impedance analysis of soil–foundation system, and a seismic response analysis of the entire soil–structure system. For the verifications, an idealized elastic soil–structure system is used to minimize variables in the comparison of the two methods. Then, the verified analysis methods are used to develop time and frequency domain models of Hualien Large-Scale Seismic Test. The predicted structural responses are compared against field measurements. The models are also analyzed with an amplified ground motion to evaluate discrepancies of the time and frequency domain analysis methods when the soil–structure system behaves beyond the elastic range. The analysis results show that the equivalent-linear frequency domain analysis method amplifies certain frequency bands and tends to result in higher structural acceleration than the nonlinear time domain analysis method. A comparison with field measurements shows that the nonlinear time domain analysis method better captures the frequency distribution of recorded structural responses than the frequency domain

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

    International Nuclear Information System (INIS)

    Heintz, Udo; Meinhart, Anton; Winkler, Andreas

    2014-01-01

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

  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. Extended and structurally supported insights into extracellular hormone binding, signal transduction and organization of the thyrotropin receptor.

    Directory of Open Access Journals (Sweden)

    Gerd Krause

    Full Text Available The hormone thyrotropin (TSH and its receptor (TSHR are crucial for the growth and function of the thyroid gland. The TSHR is evolutionary linked with the receptors of follitropin (FSHR and lutropin/choriogonadotropin (LHR and their sequences and structures are similar. The extracellular region of TSHR contains more than 350 amino acids and binds hormone and antibodies. Several important questions related to functions and mechanisms of TSHR are still not comprehensively understood. One major reason for these open questions is the lack of any structural information about the extracellular segment of TSHR that connects the N-terminal leucine-rich repeat domain (LRRD with the transmembrane helix (TMH 1, the hinge region. It has been shown experimentally that this segment is important for fine tuning of signaling and ligand interactions. A new crystal structure containing most of the extracellular hFSHR region in complex with hFSH has recently been published. Now, we have applied these new structural insights to the homologous TSHR and have generated a structural model of the TSHR LRRD/hinge-region/TSH complex. This structural model is combined and evaluated with experimental data including hormone binding (bTSH, hTSH, thyrostimulin, super-agonistic effects, antibody interactions and signaling regulation. These studies and consideration of significant and non-significant amino acids have led to a new description of mechanisms at the TSHR, including ligand-induced displacements of specific hinge region fragments. This event triggers conformational changes at a convergent center of the LRRD and the hinge region, activating an "intramolecular agonistic unit" close to the transmembrane domain.

  14. Extended and structurally supported insights into extracellular hormone binding, signal transduction and organization of the thyrotropin receptor.

    Science.gov (United States)

    Krause, Gerd; Kreuchwig, Annika; Kleinau, Gunnar

    2012-01-01

    The hormone thyrotropin (TSH) and its receptor (TSHR) are crucial for the growth and function of the thyroid gland. The TSHR is evolutionary linked with the receptors of follitropin (FSHR) and lutropin/choriogonadotropin (LHR) and their sequences and structures are similar. The extracellular region of TSHR contains more than 350 amino acids and binds hormone and antibodies. Several important questions related to functions and mechanisms of TSHR are still not comprehensively understood. One major reason for these open questions is the lack of any structural information about the extracellular segment of TSHR that connects the N-terminal leucine-rich repeat domain (LRRD) with the transmembrane helix (TMH) 1, the hinge region. It has been shown experimentally that this segment is important for fine tuning of signaling and ligand interactions. A new crystal structure containing most of the extracellular hFSHR region in complex with hFSH has recently been published. Now, we have applied these new structural insights to the homologous TSHR and have generated a structural model of the TSHR LRRD/hinge-region/TSH complex. This structural model is combined and evaluated with experimental data including hormone binding (bTSH, hTSH, thyrostimulin), super-agonistic effects, antibody interactions and signaling regulation. These studies and consideration of significant and non-significant amino acids have led to a new description of mechanisms at the TSHR, including ligand-induced displacements of specific hinge region fragments. This event triggers conformational changes at a convergent center of the LRRD and the hinge region, activating an "intramolecular agonistic unit" close to the transmembrane domain.

  15. Co-evolution of affinity and stability of grafted amyloid-motif domain antibodies.

    Science.gov (United States)

    Julian, Mark C; Lee, Christine C; Tiller, Kathryn E; Rabia, Lilia A; Day, Evan K; Schick, Arthur J; Tessier, Peter M

    2015-10-01

    An attractive approach for designing lead antibody candidates is to mimic natural protein interactions by grafting peptide recognition motifs into the complementarity-determining regions (CDRs). We are using this approach to generate single-domain (VH) antibodies specific for amyloid-forming proteins such as the Alzheimer's Aβ peptide. Here, we use random mutagenesis and yeast surface display to improve the binding affinity of a lead VH domain grafted with Aβ residues 33-42 in CDR3. Interestingly, co-selection for improved Aβ binding and VH display on the surface of yeast yields antibody domains with improved affinity and reduced stability. The highest affinity VH domains were strongly destabilized on the surface of yeast as well as unfolded when isolated as autonomous domains. In contrast, stable VH domains with improved affinity were reliably identified using yeast surface display by replacing the display antibody that recognizes a linear epitope tag at the terminus of both folded and unfolded VH domains with a conformational ligand (Protein A) that recognizes a discontinuous epitope on the framework of folded VH domains. Importantly, we find that selection for improved stability using Protein A without simultaneous co-selection for improved Aβ binding leads to strong enrichment for stabilizing mutations that reduce antigen binding. Our findings highlight the importance of simultaneously optimizing affinity and stability to improve the rapid isolation of well-folded and specific antibody fragments. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  16. The YARHG domain: an extracellular domain in search of a function.

    Directory of Open Access Journals (Sweden)

    Penny Coggill

    Full Text Available We have identified a new bacterial protein domain that we hypothesise binds to peptidoglycan. This domain is called the YARHG domain after the most highly conserved sequence-segment. The domain is found in the extracellular space and is likely to be composed of four alpha-helices. The domain is found associated with protein kinase domains, suggesting it is associated with signalling in some bacteria. The domain is also found associated with three different families of peptidases. The large number of different domains that are found associated with YARHG suggests that it is a useful functional module that nature has recombined multiple times.

  17. IgG-Fc-mediated effector functions: molecular definition of interaction sites for effector ligands and the role of glycosylation.

    Science.gov (United States)

    Jefferis, R; Lund, J; Pound, J D

    1998-06-01

    The Fc region of human IgG expresses interaction sites for many effector ligands. In this review the topographical distributions of ten of these sites are discussed in relation to functional requirement. It is apparent that interaction sites localised to the inter-CH2-CH3 domain region of the Fc allow for functional divalency, whereas sites localised to the hinge proximal region of the CH2 domain are functionally monovalent, with expression of the latter sites being particularly dependent on glycosylation. All x-ray crystal structures for Fc and Fc-ligand complexes report that the protein structure of the hinge proximal region of the CH2 domain is "disordered", suggesting "internal mobility". We propose a model in which such "internal mobility" results in the generation of a dynamic equilibrium between multiple conformers, certain of which express interaction sites specific to individual ligands. The emerging understanding of the influence of oligosaccharide/protein interactions on protein conformation and biological function of IgG antibodies suggests a potential to generate novel glycoforms of antibody molecules having unique profiles of effector functions.

  18. .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...

  19. AP-2α and AP-2β cooperatively orchestrate homeobox gene expression during branchial arch patterning.

    Science.gov (United States)

    Van Otterloo, Eric; Li, Hong; Jones, Kenneth L; Williams, Trevor

    2018-01-25

    The evolution of a hinged moveable jaw with variable morphology is considered a major factor behind the successful expansion of the vertebrates. DLX homeobox transcription factors are crucial for establishing the positional code that patterns the mandible, maxilla and intervening hinge domain, but how the genes encoding these proteins are regulated remains unclear. Herein, we demonstrate that the concerted action of the AP-2α and AP-2β transcription factors within the mouse neural crest is essential for jaw patterning. In the absence of these two proteins, the hinge domain is lost and there are alterations in the size and patterning of the jaws correlating with dysregulation of homeobox gene expression, with reduced levels of Emx, Msx and Dlx paralogs accompanied by an expansion of Six1 expression. Moreover, detailed analysis of morphological features and gene expression changes indicate significant overlap with various compound Dlx gene mutants. Together, these findings reveal that the AP-2 genes have a major function in mammalian neural crest development, influencing patterning of the craniofacial skeleton via the DLX code, an effect that has implications for vertebrate facial evolution, as well as for human craniofacial disorders. © 2018. Published by The Company of Biologists Ltd.

  20. Can Good Infection Control Be Obtained in One-stage Exchange of the Infected TKA to a Rotating Hinge Design? 10-year Results.

    Science.gov (United States)

    Zahar, Akos; Kendoff, Daniel O; Klatte, Till O; Gehrke, Thorsten A

    2016-01-01

    Prosthetic joint infection (PJI) occurs in 1% to 2% of total knee arthroplasties (TKAs). Although two-stage exchange is the preferred management method of patients with chronic PJI in TKA in North America, one-stage exchange is an alternative treatment method, but long-term studies of this approach have not been conducted. We reviewed our minimum 9-year results of 70 patients who underwent one-stage exchange arthroplasty with a rotating hinge design to determine: (1) What was the proportion of patients free of infection? (2) What was the patient rate of survival free of any reoperation? (3) What were the clinical outcomes as measured by Hospital for Special Surgery scores? (4) What proportion of patients developed radiographic evidence of loosening? All one-stage revision TKAs for infection between January 1 and December 31, 2002, with a minimum 9-year followup (mean, 10 years; range, 9-11 years), in which patients had been seen within the last 1 year, were included in this retrospective review. During that period, 11 patients with infected TKAs were treated with other approaches (including two-stage approaches in eight); the general indication for one-stage revision was the diagnosis of PJI with a known causative organism. Exclusion criteria were culture-negative preoperative aspiration, known allergy to local antibiotics or bone cement, or cases in which radical débridement was impossible as a result of the involvement of important anatomical structures. Eighty-one patients with PJI were seen during this period; 70 underwent one-stage exchange using our strict protocol and were reimplanted with a rotating hinge TKA. Eleven patients (15.7%) were lost to followup. Hospital for Special Surgery scores were recorded and all radiographs were evaluated for prosthetic loosening. Failure was defined as revision surgery for infection or any other cause. Our 10-year infection-free survival was 93% (mean, 4.1; 95% confidence interval [CI], 89%-96%; p exchange techniques for

  1. 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

  2. The BAH domain of BAF180 is required for PCNA ubiquitination

    Energy Technology Data Exchange (ETDEWEB)

    Niimi, Atsuko [Department of Genome Dynamics, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601 (Japan); Hopkins, Suzanna R; Downs, Jessica A [Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton BN1 9RQ (United Kingdom); Masutani, Chikahide, E-mail: masutani@riem.nagoya-u.ac.jp [Department of Genome Dynamics, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601 (Japan)

    2015-09-15

    Highlights: • The expression of BAF180 promotes UV-induced PCNA ubiquitination during S phase. • The BAH domains of BAF180 alone are sufficient to promote PCNA ubiquitination. • The BAH domains are not assembled into the PBAF in the absence of the C-terminus. - Abstract: Monoubiquitination of proliferating cell nuclear antigen (PCNA) is a critical regulator of post replication repair (PRR). The depletion of BAF180, a unique subunit of the PBAF chromatin remodeling complex in human cells results in reduced PCNA ubiquitination leading to less efficient fork progression following DNA damage, but little is known about the mechanism. Here, we report that the expression of exogenous BAF180 in cells promotes PCNA ubiquitination during S-phase after UV irradiation and it persists for many hours. No correlation was observed between the protein level of ubiquitin-specific protease 1 (USP1) and ubiquitinated PCNA in BAF180 expressing cells. Analysis of cells expressing BAF180 deletion mutants showed that the bromo-adjacent homology (BAH) domains are responsible for this effect. Surprisingly, a deletion construct encoding only the BAH domain region is able to increase the level of ubiquitinated PCNA, even though it is unable to be assembled into the PBAF complex. These results suggest that the ATPase-dependent chromatin remodeling activity of PBAF is not necessary, but instead the BAH domains are sufficient to promote PCNA ubiquitination.

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

    International Nuclear Information System (INIS)

    Delorme, Caroline; Joshi, Monika; Allingham, John S.

    2012-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-11-30

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

  5. A new scaling approach for the mesoscale simulation of magnetic domain structures using Monte Carlo simulations

    Energy Technology Data Exchange (ETDEWEB)

    Radhakrishnan, B., E-mail: radhakrishnb@ornl.gov; Eisenbach, M.; Burress, T.A.

    2017-06-15

    Highlights: • Developed new scaling technique for dipole–dipole interaction energy. • Developed new scaling technique for exchange interaction energy. • Used scaling laws to extend atomistic simulations to micrometer length scale. • Demonstrated transition from mono-domain to vortex magnetic structure. • Simulated domain wall width and transition length scale agree with experiments. - Abstract: A new scaling approach has been proposed for the spin exchange and the dipole–dipole interaction energy as a function of the system size. The computed scaling laws are used in atomistic Monte Carlo simulations of magnetic moment evolution to predict the transition from single domain to a vortex structure as the system size increases. The width of a 180° – domain wall extracted from the simulated structures is in close agreement with experimentally values for an F–Si alloy. The transition size from a single domain to a vortex structure is also in close agreement with theoretically predicted and experimentally measured values for Fe.

  6. Fine-grained semantic categorization across the abstract and concrete domains.

    Directory of Open Access Journals (Sweden)

    Marta Ghio

    Full Text Available A consolidated approach to the study of the mental representation of word meanings has consisted in contrasting different domains of knowledge, broadly reflecting the abstract-concrete dichotomy. More fine-grained semantic distinctions have emerged in neuropsychological and cognitive neuroscience work, reflecting semantic category specificity, but almost exclusively within the concrete domain. Theoretical advances, particularly within the area of embodied cognition, have more recently put forward the idea that distributed neural representations tied to the kinds of experience maintained with the concepts' referents might distinguish conceptual meanings with a high degree of specificity, including those within the abstract domain. Here we report the results of two psycholinguistic rating studies incorporating such theoretical advances with two main objectives: first, to provide empirical evidence of fine-grained distinctions within both the abstract and the concrete semantic domains with respect to relevant psycholinguistic dimensions; second, to develop a carefully controlled linguistic stimulus set that may be used for auditory as well as visual neuroimaging studies focusing on the parametrization of the semantic space beyond the abstract-concrete dichotomy. Ninety-six participants rated a set of 210 sentences across pre-selected concrete (mouth, hand, or leg action-related and abstract (mental state-, emotion-, mathematics-related categories, with respect either to different semantic domain-related scales (rating study 1, or to concreteness, familiarity, and context availability (rating study 2. Inferential statistics and correspondence analyses highlighted distinguishing semantic and psycholinguistic traits for each of the pre-selected categories, indicating that a simple abstract-concrete dichotomy is not sufficient to account for the entire semantic variability within either domains.

  7. Legal Challenges Related to the Regulation of a Domain Name System

    Directory of Open Access Journals (Sweden)

    Marius Kalinauskas

    2012-12-01

    Full Text Available Purpose—to review and analyse the problematic aspects related to domain name allocation and further usage processes, highlighting legal regulation of a domain name system.Design/methodology/approach—based on the comparison analysis of scientific literature, authors discuss problematic issues related to the legal regulation of domain name allocation and usage processes, analyse practical approaches and collision cases in the context of a domain name system. The authors examine the positive and negative aspects of a domain naming system and conflicting regulatory specifics. This paper describes the development of institutional bodies responsible for DNS management, supervision approaches and inner functionality policies.Findings—the authors examine domain naming system models and dispute resolution mechanisms, their evolution in the context of Internet development and the structural changes of the Internet governance institutions. The authors analyse tendencies related to DNS regulation and the possible effect of new regulation models in practice, while reflecting interests of stakeholders in the subject field.Research limitations/implications—agreements on the registration of domain names are based on self-regulation principles. A number of different interests may collide when speaking about domain name registration or usage and this issue becomes a major challenge to scientists and lawyers who are seeking an optimal domain-naming regulatory mechanism. The article does not address trademark conflicts within domain names in this respect. This should be considered as an object for separate study, which requires deeper analysis.Practical implications—the authors review key aspects of the domain name system and describe tendencies for the regulatory models.Value—the article emphasizes potential domain naming conflicts and disputes concerning the usage of common terms and phrases in order to manipulate information for illicit purposes. The

  8. Legal Challenges Related to the Regulation of a Domain Name System

    Directory of Open Access Journals (Sweden)

    Marius Kalinauskas

    2013-02-01

    Full Text Available Purpose—to review and analyse the problematic aspects related to domain name allocation and further usage processes, highlighting legal regulation of a domain name system. Design/methodology/approach—based on the comparison analysis of scientific literature, authors discuss problematic issues related to the legal regulation of domain name allocation and usage processes, analyse practical approaches and collision cases in the context of a domain name system. The authors examine the positive and negative aspects of a domain naming system and conflicting regulatory specifics. This paper describes the development of institutional bodies responsible for DNS management, supervision approaches and inner functionality policies. Findings—the authors examine domain naming system models and dispute resolution mechanisms, their evolution in the context of Internet development and the structural changes of the Internet governance institutions. The authors analyse tendencies related to DNS regulation and the possible effect of new regulation models in practice, while reflecting interests of stakeholders in the subject field. Research limitations/implications—agreements on the registration of domain names are based on self-regulation principles. A number of different interests may collide when speaking about domain name registration or usage and this issue becomes a major challenge to scientists and lawyers who are seeking an optimal domain-naming regulatory mechanism. The article does not address trademark conflicts within domain names in this respect. This should be considered as an object for separate study, which requires deeper analysis. Practical implications—the authors review key aspects of the domain name system and describe tendencies for the regulatory models. Value—the article emphasizes potential domain naming conflicts and disputes concerning the usage of common terms and phrases in order to manipulate information for illicit purposes

  9. Research and technology highlights, 1993

    Science.gov (United States)

    1994-01-01

    This report contains highlights of the major accomplishments and applications that have been made by Langley researchers and by our university and industry colleagues during the past year. The highlights illustrate both the broad range of the research and technology activities supported by NASA Langley Research Center and the contributions of this work toward maintaining United States leadership in aeronautics and space research. This report also describes some of the Center's most important research and testing facilities.

  10. ATLAS Outreach Highlights

    CERN Document Server

    Cheatham, Susan; The ATLAS collaboration

    2016-01-01

    The ATLAS outreach team is very active, promoting particle physics to a broad range of audiences including physicists, general public, policy makers, students and teachers, and media. A selection of current outreach activities and new projects will be presented. Recent highlights include the new ATLAS public website and ATLAS Open Data, the very recent public release of 1 fb-1 of ATLAS data.

  11. Difference between highlight and object colors enhances glossiness.

    Science.gov (United States)

    Hanada, Mitsuhiko

    2012-06-01

    The effect of highlight and object colors on perception of glossiness was examined. Ten participants rated glossiness of object images. The color coordinates of objects and highlights were varied while luminance of each pixel was unchanged. Four colors were used for objects and highlights. Objects were perceived as glossier when the highlight color was different from the object color than when they were the same. Objects with some unnatural combinations of highlight and object colors were perceived to be as glossy as those with natural color combinations. The results suggested that differences between highlight and object colors enhance perceived glossiness and that perceived glossiness does not depend on naturalness of color combination for highlights and objects.

  12. The C-terminal extension of human RTEL1, mutated in Hoyeraal-Hreidarsson syndrome, contains harmonin-N-like domains.

    Science.gov (United States)

    Faure, Guilhem; Revy, Patrick; Schertzer, Michael; Londono-Vallejo, Arturo; Callebaut, Isabelle

    2014-06-01

    Several studies have recently shown that germline mutations in RTEL1, an essential DNA helicase involved in telomere regulation and DNA repair, cause Hoyeraal-Hreidarsson syndrome (HHS), a severe form of dyskeratosis congenita. Using original new softwares, facilitating the delineation of the different domains of the protein and the identification of remote relationships for orphan domains, we outline here that the C-terminal extension of RTEL1, downstream of its catalytic domain and including several HHS-associated mutations, contains a yet unidentified tandem of harmonin-N-like domains, which may serve as a hub for partner interaction. This finding highlights the potential critical role of this region for the function of RTEL1 and gives insights into the impact that the identified mutations would have on the structure and function of these domains. © 2013 Wiley Periodicals, Inc.

  13. Structure of the GH1 domain of guanylate kinase-associated protein from Rattus norvegicus

    International Nuclear Information System (INIS)

    Tong, Junsen; Yang, Huiseon; Eom, Soo Hyun; Chun, ChangJu; Im, Young Jun

    2014-01-01

    Graphical abstract: - Highlights: • The crystal structure of GKAP homology domain 1 (GH1) was determined. • GKAP GH1 is a three-helix bundle connected by short flexible loops. • The predicted helix α4 associates weakly with the helix α3, suggesting dynamic nature of the GH1 domain. - Abstract: Guanylate-kinase-associated protein (GKAP) is a scaffolding protein that links NMDA receptor-PSD-95 to Shank–Homer complexes by protein–protein interactions at the synaptic junction. GKAP family proteins are characterized by the presence of a C-terminal conserved GKAP homology domain 1 (GH1) of unknown structure and function. In this study, crystal structure of the GH1 domain of GKAP from Rattus norvegicus was determined in fusion with an N-terminal maltose-binding protein at 2.0 Å resolution. The structure of GKAP GH1 displays a three-helix bundle connected by short flexible loops. The predicted helix α4 which was not visible in the crystal structure associates weakly with the helix α3 suggesting dynamic nature of the GH1 domain. The strict conservation of GH1 domain across GKAP family members and the lack of a catalytic active site required for enzyme activity imply that the GH1 domain might serve as a protein–protein interaction module for the synaptic protein clustering

  14. Structure of the GH1 domain of guanylate kinase-associated protein from Rattus norvegicus

    Energy Technology Data Exchange (ETDEWEB)

    Tong, Junsen; Yang, Huiseon [College of Pharmacy, Chonnam National University, Gwangju 500-757 (Korea, Republic of); Eom, Soo Hyun [School of Life Sciences, Steitz Center for Structural Biology, and Department of Chemistry, Gwangju Institute of Science and Technology, Gwangju 500-712 (Korea, Republic of); Chun, ChangJu, E-mail: cchun1130@jnu.ac.kr [College of Pharmacy, Chonnam National University, Gwangju 500-757 (Korea, Republic of); Im, Young Jun, E-mail: imyoungjun@jnu.ac.kr [College of Pharmacy, Chonnam National University, Gwangju 500-757 (Korea, Republic of)

    2014-09-12

    Graphical abstract: - Highlights: • The crystal structure of GKAP homology domain 1 (GH1) was determined. • GKAP GH1 is a three-helix bundle connected by short flexible loops. • The predicted helix α4 associates weakly with the helix α3, suggesting dynamic nature of the GH1 domain. - Abstract: Guanylate-kinase-associated protein (GKAP) is a scaffolding protein that links NMDA receptor-PSD-95 to Shank–Homer complexes by protein–protein interactions at the synaptic junction. GKAP family proteins are characterized by the presence of a C-terminal conserved GKAP homology domain 1 (GH1) of unknown structure and function. In this study, crystal structure of the GH1 domain of GKAP from Rattus norvegicus was determined in fusion with an N-terminal maltose-binding protein at 2.0 Å resolution. The structure of GKAP GH1 displays a three-helix bundle connected by short flexible loops. The predicted helix α4 which was not visible in the crystal structure associates weakly with the helix α3 suggesting dynamic nature of the GH1 domain. The strict conservation of GH1 domain across GKAP family members and the lack of a catalytic active site required for enzyme activity imply that the GH1 domain might serve as a protein–protein interaction module for the synaptic protein clustering.

  15. 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.

  16. Rashba spin–orbit coupling effects on a current-induced domain wall motion

    International Nuclear Information System (INIS)

    Ryu, Jisu; Seo, Soo-Man; Lee, Kyung-Jin; Lee, Hyun-Woo

    2012-01-01

    A current-induced domain wall motion in magnetic nanowires with a strong structural inversion asymmetry [I.M. Miron, T. Moore, H. Szambolics, L.D. Buda-Prejbeanu, S. Auffret, B. Rodmacq, S. Pizzini, J. Vogel, M. Bonfim, A. Schuhl, G. Gaudin, Nat. Mat. 10 (2011) 419] seems to have novel features such as the domain wall motion along the current direction or the delay of the onset of the Walker breakdown. In such a highly asymmetric system, the Rashba spin–orbit coupling (RSOC) may affect a domain wall motion. We studied theoretically the RSOC effects on a domain wall motion and found that the RSOC, indeed, can induce the domain wall motion along the current direction in certain situations. It also delays the Walker breakdown and for a strong RSOC, the Walker breakdown does not occur at all. The RSOC effects are sensitive to the magnetic anisotropy of nanowires and also to the ratio between the Gilbert damping parameter α and the non-adiabaticity parameter β. - Highlights: ► Effects of Rashba spin–orbit coupling on a domain wall motion is calculated. ► The effects depend highly on the anisotropy of a magnetic system. ► It modifies the wall velocity for the system with a perpendicular magnetic anisotropy. ► The modified velocity can be along the current direction in certain situations. ► Rashba spin–orbit coupling also hinders the onset of the Walker breakdown.

  17. Modified random hinge transport mechanics and multiple scattering step-size selection in EGS5

    International Nuclear Information System (INIS)

    Wilderman, S.J.; Bielajew, A.F.

    2005-01-01

    The new transport mechanics in EGS5 allows for significantly longer electron transport step sizes and hence shorter computation times than required for identical problems in EGS4. But as with all Monte Carlo electron transport algorithms, certain classes of problems exhibit step-size dependencies even when operating within recommended ranges, sometimes making selection of step-sizes a daunting task for novice users. Further contributing to this problem, because of the decoupling of multiple scattering and continuous energy loss in the dual random hinge transport mechanics of EGS5, there are two independent step sizes in EGS5, one for multiple scattering and one for continuous energy loss, each of which influences speed and accuracy in a different manner. Further, whereas EGS4 used a single value of fractional energy loss (ESTEPE) to determine step sizes at all energies, to increase performance by decreasing the amount of effort expended simulating lower energy particles, EGS5 permits the fractional energy loss values which are used to determine both the multiple scattering and continuous energy loss step sizes to vary with energy. This results in requiring the user to specify four fractional energy loss values when optimizing computations for speed. Thus, in order to simplify step-size selection and to mitigate step-size dependencies, a method has been devised to automatically optimize step-size selection based on a single material dependent input related to the size of problem tally region. In this paper we discuss the new transport mechanics in EGS5 and describe the automatic step-size optimization algorithm. (author)

  18. Gravitational Waves and Time Domain Astronomy

    Science.gov (United States)

    Centrella, Joan; Nissanke, Samaya; Williams, Roy

    2012-01-01

    The gravitational wave window onto the universe will open in roughly five years, when Advanced LIGO and Virgo achieve the first detections of high frequency gravitational waves, most likely coming from compact binary mergers. Electromagnetic follow-up of these triggers, using radio, optical, and high energy telescopes, promises exciting opportunities in multi-messenger time domain astronomy. In the decade, space-based observations of low frequency gravitational waves from massive black hole mergers, and their electromagnetic counterparts, will open up further vistas for discovery. This two-part workshop featured brief presentations and stimulating discussions on the challenges and opportunities presented by gravitational wave astronomy. Highlights from the workshop, with the emphasis on strategies for electromagnetic follow-up, are presented in this report.

  19. Extended HSR/CARD domain mediates AIRE binding to DNA

    Energy Technology Data Exchange (ETDEWEB)

    Maslovskaja, Julia, E-mail: julia.maslovskaja@ut.ee; Saare, Mario; Liiv, Ingrid; Rebane, Ana; Peterson, Pärt

    2015-12-25

    Autoimmune regulator (AIRE) activates the transcription of many genes in an unusual promiscuous and stochastic manner. The mechanism by which AIRE binds to the chromatin and DNA is not fully understood, and the regulatory elements that AIRE target genes possess are not delineated. In the current study, we demonstrate that AIRE activates the expression of transiently transfected luciferase reporters that lack defined promoter regions, as well as intron and poly(A) signal sequences. Our protein-DNA interaction experiments with mutated AIRE reveal that the intact homogeneously staining region/caspase recruitment domain (HSR/CARD) and amino acids R113 and K114 are key elements involved in AIRE binding to DNA. - Highlights: • Promoter and mRNA processing elements are not important for AIRE to activate gene expression from reporter plasmids. • AIRE protein fragment aa 1–138 mediates direct binding to DNA. • Integrity of the HSR/CARD domain is needed for AIRE binding to DNA.

  20. Extended HSR/CARD domain mediates AIRE binding to DNA

    International Nuclear Information System (INIS)

    Maslovskaja, Julia; Saare, Mario; Liiv, Ingrid; Rebane, Ana; Peterson, Pärt

    2015-01-01

    Autoimmune regulator (AIRE) activates the transcription of many genes in an unusual promiscuous and stochastic manner. The mechanism by which AIRE binds to the chromatin and DNA is not fully understood, and the regulatory elements that AIRE target genes possess are not delineated. In the current study, we demonstrate that AIRE activates the expression of transiently transfected luciferase reporters that lack defined promoter regions, as well as intron and poly(A) signal sequences. Our protein-DNA interaction experiments with mutated AIRE reveal that the intact homogeneously staining region/caspase recruitment domain (HSR/CARD) and amino acids R113 and K114 are key elements involved in AIRE binding to DNA. - Highlights: • Promoter and mRNA processing elements are not important for AIRE to activate gene expression from reporter plasmids. • AIRE protein fragment aa 1–138 mediates direct binding to DNA. • Integrity of the HSR/CARD domain is needed for AIRE binding to DNA.

  1. Engineering an improved IgG4 molecule with reduced disulfide bond heterogeneity and increased Fab domain thermal stability.

    Science.gov (United States)

    Peters, Shirley J; Smales, C Mark; Henry, Alistair J; Stephens, Paul E; West, Shauna; Humphreys, David P

    2012-07-13

    The integrity of antibody structure, stability, and biophysical characterization are becoming increasingly important as antibodies receive increasing scrutiny from regulatory authorities. We altered the disulfide bond arrangement of an IgG4 molecule by mutation of the Cys at the N terminus of the heavy chain constant domain 1 (C(H)1) (Kabat position 127) to a Ser and introduction of a Cys at a variety of positions (positions 227-230) at the C terminus of C(H)1. An inter-LC-C(H)1 disulfide bond is thus formed, which mimics the disulfide bond arrangement found in an IgG1 molecule. The antibody species present in the supernatant following transient expression in Chinese hamster ovary cells were analyzed by immunoblot to investigate product homogeneity, and purified product was analyzed by a thermofluor assay to determine thermal stability. We show that the light chain can form an inter-LC-C(H)1 disulfide bond with a Cys when present at several positions on the upper hinge (positions 227-230) and that such engineered disulfide bonds can consequently increase the Fab domain thermal stability between 3 and 6.8 °C. The IgG4 disulfide mutants displaying the greatest increase in Fab thermal stability were also the most homogeneous in terms of disulfide bond arrangement and antibody species present. Importantly, mutations did not affect the affinity for antigen of the resultant molecules. In combination with the previously described S241P mutation, we present an IgG4 molecule with increased Fab thermal stability and reduced product heterogeneity that potentially offers advantages for the production of IgG4 molecules.

  2. Understanding stripe domains in Permalloy films via the angular dependence of permeability spectra

    Energy Technology Data Exchange (ETDEWEB)

    Wei, Jinwu; Feng, Hongmei; Zhu, Zengtai; Song, Chengkun; Wang, Xiangqian; Liu, Qingfang [Key Laboratory for Magnetism and Magnetic Materials of the Ministry of Education, Lanzhou University, Lanzhou 730000 (China); Wang, Jianbo, E-mail: wangjb@lzu.edu.cn [Key Laboratory for Magnetism and Magnetic Materials of the Ministry of Education, Lanzhou University, Lanzhou 730000 (China); Key Laboratory for Special Function Materials and Structural Design of the Ministry of the Education, Lanzhou University, Lanzhou 730000 (China)

    2017-06-15

    Highlights: • A phenomenological model is proposed to analyze the angular dependence of the μ″{sub max}. • The maximum canting angle θ{sub 0} in the stripe domain structure can be estimated. • Micromagnetic simulation results are nearly in accordance with the experimental results. - Abstract: An investigation of the angular dependence of the dynamic permeability spectra has been performed. Three Permalloy films with different thickness were used as the study samples that possess the stripe domains. In order to better understand the magnetization distribution in stripe domains, a theoretical approach was proposed to analyze the variation of the resonance intensity of permeability spectra. By fitting the angular dependence of the μ″{sub max} using a theoretical function, a coefficient Λ that can be used to evaluate the average value of the periodic function of the anting angle θ in a periodic stripe is obtained. As the film thickness increases, the decrease of the ratio between domain wall width and stripe domain width is happen. This enables that the coefficient Λ decreases with the increase of film thickness. By deducing this coefficient Λ, one can estimate the maximum canting angle θ{sub 0} ∼ 8° for the Permalloy films in our experiments.

  3. Domain decomposition method for solving elliptic problems in unbounded domains

    International Nuclear Information System (INIS)

    Khoromskij, B.N.; Mazurkevich, G.E.; Zhidkov, E.P.

    1991-01-01

    Computational aspects of the box domain decomposition (DD) method for solving boundary value problems in an unbounded domain are discussed. A new variant of the DD-method for elliptic problems in unbounded domains is suggested. It is based on the partitioning of an unbounded domain adapted to the given asymptotic decay of an unknown function at infinity. The comparison of computational expenditures is given for boundary integral method and the suggested DD-algorithm. 29 refs.; 2 figs.; 2 tabs

  4. Two-Dimensional Micro-/Nanoradian Angle Generator with High Resolution and Repeatability Based on Piezo-Driven Double-Axis Flexure Hinge and Three Capacitive Sensors.

    Science.gov (United States)

    Tan, Xinran; Zhu, Fan; Wang, Chao; Yu, Yang; Shi, Jian; Qi, Xue; Yuan, Feng; Tan, Jiubin

    2017-11-19

    This study presents a two-dimensional micro-/nanoradian angle generator (2D-MNAG) that achieves high angular displacement resolution and repeatability using a piezo-driven flexure hinge for two-dimensional deflections and three capacitive sensors for output angle monitoring and feedback control. The principal error of the capacitive sensor for precision microangle measurement is analyzed and compensated for; so as to achieve a high angle output resolution of 10 nrad (0.002 arcsec) and positioning repeatability of 120 nrad (0.024 arcsec) over a large angular range of ±4363 μrad (±900 arcsec) for the 2D-MNAG. The impact of each error component, together with the synthetic error of the 2D-MNAG after principal error compensation are determined using Monte Carlo simulation for further improvement of the 2D-MNAG.

  5. The SHOCT domain: a widespread domain under-represented in model organisms.

    Directory of Open Access Journals (Sweden)

    Ruth Y Eberhardt

    Full Text Available We have identified a new protein domain, which we have named the SHOCT domain (Short C-terminal domain. This domain is widespread in bacteria with over a thousand examples. But we found it is missing from the most commonly studied model organisms, despite being present in closely related species. It's predominantly C-terminal location, co-occurrence with numerous other domains and short size is reminiscent of the Gram-positive anchor motif, however it is present in a much wider range of species. We suggest several hypotheses about the function of SHOCT, including oligomerisation and nucleic acid binding. Our initial experiments do not support its role as an oligomerisation domain.

  6. Structure and catalytic regulatory function of ubiquitin specific protease 11 N-terminal and ubiquitin-like domains.

    Science.gov (United States)

    Harper, Stephen; Gratton, Hayley E; Cornaciu, Irina; Oberer, Monika; Scott, David J; Emsley, Jonas; Dreveny, Ingrid

    2014-05-13

    The ubiquitin specific protease 11 (USP11) is implicated in DNA repair, viral RNA replication, and TGFβ signaling. We report the first characterization of the USP11 domain architecture and its role in regulating the enzymatic activity. USP11 consists of an N-terminal "domain present in USPs" (DUSP) and "ubiquitin-like" (UBL) domain, together referred to as DU domains, and the catalytic domain harboring a second UBL domain. Crystal structures of the DU domains show a tandem arrangement with a shortened β-hairpin at the two-domain interface and altered surface characteristics compared to the homologues USP4 and USP15. A conserved VEVY motif is a signature feature at the two-domain interface that shapes a potential protein interaction site. Small angle X-ray scattering and gel filtration experiments are consistent with the USP11DU domains and full-length USP11 being monomeric. Unexpectedly, we reveal, through kinetic assays of a series of deletion mutants, that the catalytic activity of USP11 is not regulated through intramolecular autoinhibition or activation by the N-terminal DU or UBL domains. Moreover, ubiquitin chain cleavage assays with all eight linkages reveal a preference for Lys(63)-, Lys(6)-, Lys(33)-, and Lys(11)-linked chains over Lys(27)-, Lys(29)-, and Lys(48)-linked and linear chains consistent with USP11's function in DNA repair pathways that is mediated by the protease domain. Our data support a model whereby USP11 domains outside the catalytic core domain serve as protein interaction or trafficking modules rather than a direct regulatory function of the proteolytic activity. This highlights the diversity of USPs in substrate recognition and regulation of ubiquitin deconjugation.

  7. 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.

  8. Highlighting continued uncertainty in global land cover maps for the user community

    International Nuclear Information System (INIS)

    Fritz, Steffen; See, Linda; McCallum, Ian; Schill, Christian; Obersteiner, Michael; Van der Velde, Marijn; Boettcher, Hannes; Havlík, Petr; Achard, Frédéric

    2011-01-01

    In the last 10 years a number of new global datasets have been created and new, more sophisticated algorithms have been designed to classify land cover. GlobCover and MODIS v.5 are the most recent global land cover products available, where GlobCover (300 m) has the finest spatial resolution of other comparable products such as MODIS v.5 (500 m) and GLC-2000 (1 km). This letter shows that the thematic accuracy in the cropland domain has decreased when comparing these two latest products. This disagreement is also evident spatially when examining maps of cropland and forest disagreement between GLC-2000, MODIS and GlobCover. The analysis highlights the continued uncertainty surrounding these products, with a combined forest and cropland disagreement of 893 Mha (GlobCover versus MODIS v.5). This letter suggests that data sharing efforts and the provision of more in situ data for training, calibration and validation are very important conditions for improving future global land cover products.

  9. Fast conformational exchange between the sulfur-free and persulfide-bound rhodanese domain of E. coli YgaP

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Wei [Hefei National Laboratory for Physical Sciences at the Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026 (China); Zhou, Peng [High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei, Anhui 230031 (China); He, Yao; Yu, Lu; Xiong, Ying [Hefei National Laboratory for Physical Sciences at the Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026 (China); Tian, Changlin, E-mail: cltian@ustc.edu.cn [Hefei National Laboratory for Physical Sciences at the Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026 (China); High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei, Anhui 230031 (China); Wu, Fangming, E-mail: fmwu@hmfl.ac.cn [High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei, Anhui 230031 (China)

    2014-09-26

    Highlights: • Three dimensional solution NMR structure of YgaP rhodanese domain. • Function validation of YgaP rhodanese domain to substrate Na{sub 2}S{sub 2}O{sub 3}. • Fast exchange between the intact and persulfide-intermediate rhodanese domain. - Abstract: Rhodanese domains are abundant structural modules that catalyze the transfer of a sulfur atom from thiolsulfates to cyanide via formation of a covalent persulfide intermediate that is bound to an essential conserved cysteine residue. In this study, the three-dimensional structure of the rhodanese domain of YgaP from Escherichia coli was determined using solution NMR. A typical rhodanese domain fold was observed, as expected from the high homology with the catalytic domain of other sulfur transferases. The initial sulfur-transfer step and formation of the rhodanese persulfide intermediate were monitored by addition of sodium thiosulfate using two-dimensional {sup 1}H–{sup 15}N correlation spectroscopy. Discrete sharp signals were observed upon substrate addition, indicting fast exchange between sulfur-free and persulfide-intermediate forms. Residues exhibiting pronounced chemical shift changes were mapped to the structure, and included both substrate binding and surrounding residues.

  10. Computational study of the Risoe-B1-18 airfoil with a hinged flap providing variable trailing edge geometry

    Energy Technology Data Exchange (ETDEWEB)

    Troldborg, N.

    2005-03-01

    A comprehensive computational study, in both steady and unsteady flow conditions, has been carried out to investigate the aerodynamic characteristics of the Risoe-B1-18 airfoil equipped with variable trailing edge geometry as produced by a hinged flap. The function of such flaps should be to decrease fatigue-inducing oscillations on the blades. The computations were conducted using a 2D incompressible RANS solver with a k-w turbulence model under the assumption of a fully developed turbulent flow. The investigations were conducted at a Reynolds number of Re = 1.6 - 10{sup 6}. Calculations conducted on the baseline airfoil showed excellent agreement with measurements on the same airfoil with the same specified conditions. Furthermore, a more widespread comparison with an advanced potential theory code is presented. The influence of various key parameters, such as flap shape, flap size and oscillating frequencies, was investigated so that an optimum design can be suggested for application with wind turbine blades. It is concluded that a moderately curved flap with flap chord to airfoil curve ratio between 0.05 and 0.10 would be an optimum choice. (author)

  11. MIT domain of Vps4 is a Ca2+-dependent phosphoinositide-binding domain.

    Science.gov (United States)

    Iwaya, Naoko; Takasu, Hirotoshi; Goda, Natsuko; Shirakawa, Masahiro; Tanaka, Toshiki; Hamada, Daizo; Hiroaki, Hidekazu

    2013-05-01

    The microtubule interacting and trafficking (MIT) domain is a small protein module that is conserved in proteins of diverged function, such as Vps4, spastin and sorting nexin 15 (SNX15). The molecular function of the MIT domain is protein-protein interaction, in which the domain recognizes peptides containing MIT-interacting motifs. Recently, we identified an evolutionarily related domain, 'variant' MIT domain at the N-terminal region of the microtubule severing enzyme katanin p60. We found that the domain was responsible for binding to microtubules and Ca(2+). Here, we have examined whether the authentic MIT domains also bind Ca(2+). We found that the loop between the first and second α-helices of the MIT domain binds a Ca(2+) ion. Furthermore, the MIT domains derived from Vps4b and SNX15a showed phosphoinositide-binding activities in a Ca(2+)-dependent manner. We propose that the MIT domain is a novel membrane-associating domain involved in endosomal trafficking.

  12. The NIMH Research Domain Criteria Initiative: Background, Issues, and Pragmatics.

    Science.gov (United States)

    Kozak, Michael J; Cuthbert, Bruce N

    2016-03-01

    This article describes the National Institute of Mental Health's Research Domain Criteria (RDoC) initiative. The description includes background, rationale, goals, and the way the initiative has been developed and organized. The central RDoC concepts are summarized and the current matrix of constructs that have been vetted by workshops of extramural scientists is depicted. A number of theoretical and methodological issues that can arise in connection with the nature of RDoC constructs are highlighted: subjectivism and heterophenomenology, desynchrony and theoretical neutrality among units of analysis, theoretical reductionism, endophenotypes, biomarkers, neural circuits, construct "grain size," and analytic challenges. The importance of linking RDoC constructs to psychiatric clinical problems is discussed. Some pragmatics of incorporating RDoC concepts into applications for NIMH research funding are considered, including sampling design. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

  13. Working mechanism of immunoglobulin A1 (IgA1) protease: cleavage of IgA1 antibody to Neisseria meningitidis PorA requires de novo synthesis of IgA1 Protease

    DEFF Research Database (Denmark)

    Vidarsson, G; Overbeeke, N; Stemerding, AM

    2005-01-01

    Neisseria meningitidis secretes a protease that specifically cleaves the hinge region of immunoglobulin A1 (IgA1), releasing the effector (Fc) domain of IgA1 from the antigen binding (Fab) determinants. Theoretically, the remaining Fab fragments can block pathogen receptors or toxins and still...

  14. Working mechanism of immunoglobulin A1 (IgA1) protease: cleavage of IgA1 antibody to Neisseria meningitidis PorA requires de novo synthesis of IgA1 Protease

    NARCIS (Netherlands)

    Vidarsson, Gestur; Overbeeke, Natasja; Stemerding, Annette M.; van den Dobbelsteen, Germie; van Ulsen, Peter; van der Ley, Peter; Kilian, Mogens; van de Winkel, Jan G. J.

    2005-01-01

    Neisseria meningitidis secretes a protease that specifically cleaves the hinge region of immunoglobulin A1 (IgA1), releasing the effector (Fc) domain of IgA1 from the antigen binding (Fab) determinants. Theoretically, the remaining Fab fragments can block pathogen receptors or toxins and still

  15. 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.

  16. Structures of a Nonribosomal Peptide Synthetase Module Bound to MbtH-like Proteins Support a Highly Dynamic Domain Architecture

    Energy Technology Data Exchange (ETDEWEB)

    Miller, Bradley R.; Drake, Eric J.; Shi, Ce; Aldrich, Courtney C.; Gulick, Andrew M. (UMM); (HWMRI)

    2016-09-05

    Nonribosomal peptide synthetases (NRPSs) produce a wide variety of peptide natural products. During synthesis, the multidomain NRPSs act as an assembly line, passing the growing product from one module to the next. Each module generally consists of an integrated peptidyl carrier protein, an amino acid-loading adenylation domain, and a condensation domain that catalyzes peptide bond formation. Some adenylation domains interact with small partner proteins called MbtH-like proteins (MLPs) that enhance solubility or activity. A structure of an MLP bound to an adenylation domain has been previously reported using a truncated adenylation domain, precluding any insight that might be derived from understanding the influence of the MLP on the intact adenylation domain or on the dynamics of the entire NRPS module. Here, we present the structures of the full-length NRPS EntF bound to the MLPs from Escherichia coli and Pseudomonas aeruginosa. These new structures, along with biochemical and bioinformatics support, further elaborate the residues that define the MLP-adenylation domain interface. Additionally, the structures highlight the dynamic behavior of NRPS modules, including the module core formed by the adenylation and condensation domains as well as the orientation of the mobile thioesterase domain.

  17. Brookhaven highlights, 1986-1987

    International Nuclear Information System (INIS)

    Rowe, M.S.

    1988-01-01

    The highlights of research conducted between October 1985 and September 1987 at Brookhaven National Laboratory are reviewed in this publication. Also covered are the administrative and financial status of the laboratory and a brief mention of meetings held and honors received. (FI)

  18. Inhibition of αIIbβ3 Ligand Binding by an αIIb Peptide that Clasps the Hybrid Domain to the βI Domain of β3.

    Directory of Open Access Journals (Sweden)

    Wen Hwa Lee

    Full Text Available Agonist-stimulated platelet activation triggers conformational changes of integrin αIIbβ3, allowing fibrinogen binding and platelet aggregation. We have previously shown that an octapeptide, p1YMESRADR8, corresponding to amino acids 313-320 of the β-ribbon extending from the β-propeller domain of αIIb, acts as a potent inhibitor of platelet aggregation. Here we have performed in silico modelling analysis of the interaction of this peptide with αIIbβ3 in its bent and closed (not swing-out conformation and show that the peptide is able to act as a substitute for the β-ribbon by forming a clasp restraining the β3 hybrid and βI domains in a closed conformation. The involvement of species-specific residues of the β3 hybrid domain (E356 and K384 and the β1 domain (E297 as well as an intrapeptide bond (pE315-pR317 were confirmed as important for this interaction by mutagenesis studies of αIIbβ3 expressed in CHO cells and native or substituted peptide inhibitory studies on platelet functions. Furthermore, NMR data corroborate the above results. Our findings provide insight into the important functional role of the αIIb β-ribbon in preventing integrin αIIbβ3 head piece opening, and highlight a potential new therapeutic approach to prevent integrin ligand binding.

  19. Conversion of Dielectric Data from the Time Domain to the Frequency Domain

    Directory of Open Access Journals (Sweden)

    Vladimir Durman

    2005-01-01

    Full Text Available Polarisation and conduction processes in dielectric systems can be identified by the time domain or the frequency domain measurements. If the systems is a linear one, the results of the time domain measurements can be transformed into the frequency domain, and vice versa. Commonly, the time domain data of the absorption conductivity are transformed into the frequency domain data of the dielectric susceptibility. In practice, the relaxation are mainly evaluated by the frequency domain data. In the time domain, the absorption current measurement were prefered up to now. Recent methods are based on the recovery voltage measurements. In this paper a new method of the recovery data conversion from the time the frequency domain is proposed. The method is based on the analysis of the recovery voltage transient based on the Maxwell equation for the current density in a dielectric. Unlike the previous published solutions, the Laplace fransform was used to derive a formula suitable for practical purposes. the proposed procedure allows also calculating of the insulation resistance and separating the polarisation and conduction losses.

  20. Predicting detection performance with model observers: Fourier domain or spatial domain?

    Science.gov (United States)

    Chen, Baiyu; Yu, Lifeng; Leng, Shuai; Kofler, James; Favazza, Christopher; Vrieze, Thomas; McCollough, Cynthia

    2016-02-27

    The use of Fourier domain model observer is challenged by iterative reconstruction (IR), because IR algorithms are nonlinear and IR images have noise texture different from that of FBP. A modified Fourier domain model observer, which incorporates nonlinear noise and resolution properties, has been proposed for IR and needs to be validated with human detection performance. On the other hand, the spatial domain model observer is theoretically applicable to IR, but more computationally intensive than the Fourier domain method. The purpose of this study is to compare the modified Fourier domain model observer to the spatial domain model observer with both FBP and IR images, using human detection performance as the gold standard. A phantom with inserts of various low contrast levels and sizes was repeatedly scanned 100 times on a third-generation, dual-source CT scanner at 5 dose levels and reconstructed using FBP and IR algorithms. The human detection performance of the inserts was measured via a 2-alternative-forced-choice (2AFC) test. In addition, two model observer performances were calculated, including a Fourier domain non-prewhitening model observer and a spatial domain channelized Hotelling observer. The performance of these two mode observers was compared in terms of how well they correlated with human observer performance. Our results demonstrated that the spatial domain model observer correlated well with human observers across various dose levels, object contrast levels, and object sizes. The Fourier domain observer correlated well with human observers using FBP images, but overestimated the detection performance using IR images.

  1. Development and evaluation of single domain antibodies for vaccinia and the L1 antigen.

    Directory of Open Access Journals (Sweden)

    Scott A Walper

    Full Text Available There is ongoing interest to develop high affinity, thermal stable recognition elements to replace conventional antibodies in biothreat detection assays. As part of this effort, single domain antibodies that target vaccinia virus were developed. Two llamas were immunized with killed viral particles followed by boosts with the recombinant membrane protein, L1, to stimulate the immune response for envelope and membrane proteins of the virus. The variable domains of the induced heavy chain antibodies were selected from M13 phage display libraries developed from isolated RNA. Selection via biopanning on the L1 antigen produced single domain antibodies that were specific and had affinities ranging from 4×10(-9 M to 7.0×10(-10 M, as determined by surface plasmon resonance. Several showed good ability to refold after heat denaturation. These L1-binding single domain antibodies, however, failed to recognize the killed vaccinia antigen. Useful vaccinia binding single domain antibodies were isolated by a second selection using the killed virus as the target. The virus binding single domain antibodies were incorporated in sandwich assays as both capture and tracer using the MAGPIX system yielding limits of detection down to 4×10(5 pfu/ml, a four-fold improvement over the limit obtained using conventional antibodies. This work demonstrates the development of anti-vaccinia single domain antibodies and their incorporation into sandwich assays for viral detection. It also highlights the properties of high affinity and thermal stability that are hallmarks of single domain antibodies.

  2. The Enzyme-Like Domain of Arabidopsis Nuclear β-Amylases Is Critical for DNA Sequence Recognition and Transcriptional Activation.

    Science.gov (United States)

    Soyk, Sebastian; Simková, Klára; Zürcher, Evelyne; Luginbühl, Leonie; Brand, Luise H; Vaughan, Cara K; Wanke, Dierk; Zeeman, Samuel C

    2014-04-01

    Plant BZR1-BAM transcription factors contain a β-amylase (BAM)-like domain, characteristic of proteins involved in starch breakdown. The enzyme-derived domains appear to be noncatalytic, but they determine the function of the two Arabidopsis thaliana BZR1-BAM isoforms (BAM7 and BAM8) during transcriptional initiation. Removal or swapping of the BAM domains demonstrates that the BAM7 BAM domain restricts DNA binding and transcriptional activation, while the BAM8 BAM domain allows both activities. Furthermore, we demonstrate that BAM7 and BAM8 interact on the protein level and cooperate during transcriptional regulation. Site-directed mutagenesis of residues in the BAM domain of BAM8 shows that its function as a transcriptional activator is independent of catalysis but requires an intact substrate binding site, suggesting it may bind a ligand. Microarray experiments with plants overexpressing truncated versions lacking the BAM domain indicate that the pseudo-enzymatic domain increases selectivity for the preferred cis-regulatory element BBRE (BZR1-BAM Responsive Element). Side specificity toward the G-box may allow crosstalk to other signaling networks. This work highlights the importance of the enzyme-derived domain of BZR1-BAMs, supporting their potential role as metabolic sensors. © 2014 American Society of Plant Biologists. All rights reserved.

  3. Studies Highlight Biodiesel's Benefits

    Science.gov (United States)

    , Colo., July 6, 1998 — Two new studies highlight the benefits of biodiesel in reducing overall air Energy's National Renewable Energy Laboratory (NREL) conducted both studies: An Overview of Biodiesel and Petroleum Diesel Life Cycles and Biodiesel Research Progress, 1992-1997. Biodiesel is a renewable diesel

  4. The influence of punching process on residual stress and magnetic domain structure of non-oriented silicon steel

    International Nuclear Information System (INIS)

    Cao, Hongzhi; Hao, Linpo; Yi, Jingwen; Zhang, Xianglin; Luo, Zhonghan; Chen, Shenglin; Li, Rongfeng

    2016-01-01

    The main purpose of this paper is to investigate the influence of punching process on residual stress and magnetic domain structure. The residual stress in non-oriented silicon steel after punching process was measured by nanoindentation. The maximum depth was kept constant as 300 nm during nanoindentation. The material around indentation region exhibited no significant pile-up deformation. The calculation of residual stress was based on the Suresh theoretical model. Our experimental results show that residual compressive stress was generated around the sheared edge after punching. The width of residual stress affected zone by punching was around 0.4–0.5 mm. After annealing treatment, the residual stress was significantly decreased. Magnetic domain structure was observed according to the Bitter method. The un-annealed sample exhibited complicated domain patterns, and the widths of the magnetic domains varied between 3 µm and 8 µm. Most of the domain patterns of the annealed sample were 180°-domains and 90°-domains, and the widths of the domains decreased to 1–3 µm. - Highlights: • The residual stress distribution on sheared edge was measured. • The residual compressive stress was generated around the sheared edge. • The width of residual stress affected zone was about 0.4–0.5 mm. • The shape and width of the domain structure would be changed by annealing.

  5. Magnetization reversal of the transverse domain wall confined between two clusters of magnetic impurities in a ferromagnetic planar nanowire

    Energy Technology Data Exchange (ETDEWEB)

    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); Leonel, S.A., E-mail: sidiney@fisica.ufjf.br [Departamento de Física, Laboratório de Simulação Computacional, Universidade Federal de Juiz de Fora, Juiz de Fora, Minas Gerais 36036–330 (Brazil); Coura, P.Z., E-mail: pablo@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., E-mail: sjfsato@fisica.ufjf.br [Departamento de Física, Laboratório de Simulação Computacional, Universidade Federal de Juiz de Fora, Juiz de Fora, Minas Gerais 36036–330 (Brazil); Costa, B.V., E-mail: bvc@fisica.ufmg.br [Departamento de Física, Laboratório de Simulação, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 30123–970 (Brazil); Vázquez, M., E-mail: mvazquez@icmm.csic.es [Instituto de Ciencia de Materiales de Madrid, CSIC. 28049 Madrid (Spain)

    2016-12-01

    Numerical simulations have been used to investigate the polarity reversal of the transverse domain wall in rectangular magnetic nanowires and the stabilization of the domain wall position after occurring the polarity reversal. In order to control the wall position we have considered two clusters of magnetic impurities, identical and equidistant from the nanowire width axis. Traps of pinning and blocking for the transverse domain wall can be originated from magnetic impurities, consisting of a local variation of the exchange constant. Under suitable excitation amplitudes it is possible to switch the polarity of the transverse domain wall by applying a nanosecond axial magnetic field pulse in a fast and controllable way. - Highlights: • Traps for pinning and blocking transverse domain walls are proposed. • The traps consisting of localized modifications of the magnetic properties. • The wall polarity can be reversed in a fast and controllable way.

  6. 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.

  7. Glycosaminoglycans are interactants of Langerin: comparison with gp120 highlights an unexpected calcium-independent binding mode.

    Science.gov (United States)

    Chabrol, Eric; Nurisso, Alessandra; Daina, Antoine; Vassal-Stermann, Emilie; Thepaut, Michel; Girard, Eric; Vivès, Romain R; Fieschi, Franck

    2012-01-01

    Langerin is a C-type lectin specifically expressed in Langerhans cells. As recently shown for HIV, Langerin is thought to capture pathogens and mediate their internalisation into Birbeck Granules for elimination. However, the precise functions of Langerin remain elusive, mostly because of the lack of information on its binding properties and physiological ligands. Based on recent reports that Langerin binds to sulfated sugars, we conducted here a comparative analysis of Langerin interaction with mannose-rich HIV glycoprotein gp120 and glycosaminoglycan (GAGs), a family of sulfated polysaccharides expressed at the surface of most mammalian cells. Our results first revealed that Langerin bound to these different glycans through very distinct mechanisms and led to the identification of a novel, GAG-specific binding mode within Langerin. In contrast to the canonical lectin domain, this new binding site showed no Ca(2+)-dependency, and could only be detected in entire, trimeric extracellular domains of Langerin. Interestingly binding to GAGs, did not simply rely on a net charge effect, but rather on more discrete saccharide features, such as 6-O-sulfation, or iduronic acid content. Using molecular modelling simulations, we proposed a model of Langerin/heparin complex, which located the GAG binding site at the interface of two of the three Carbohydrate-recognition domains of the protein, at the edge of the a-helix coiled-coil. To our knowledge, the binding properties that we have highlighted here for Langerin, have never been reported for C-type lectins before. These findings provide new insights towards the understanding of Langerin biological functions.

  8. Glycosaminoglycans are interactants of Langerin: comparison with gp120 highlights an unexpected calcium-independent binding mode.

    Directory of Open Access Journals (Sweden)

    Eric Chabrol

    Full Text Available Langerin is a C-type lectin specifically expressed in Langerhans cells. As recently shown for HIV, Langerin is thought to capture pathogens and mediate their internalisation into Birbeck Granules for elimination. However, the precise functions of Langerin remain elusive, mostly because of the lack of information on its binding properties and physiological ligands. Based on recent reports that Langerin binds to sulfated sugars, we conducted here a comparative analysis of Langerin interaction with mannose-rich HIV glycoprotein gp120 and glycosaminoglycan (GAGs, a family of sulfated polysaccharides expressed at the surface of most mammalian cells. Our results first revealed that Langerin bound to these different glycans through very distinct mechanisms and led to the identification of a novel, GAG-specific binding mode within Langerin. In contrast to the canonical lectin domain, this new binding site showed no Ca(2+-dependency, and could only be detected in entire, trimeric extracellular domains of Langerin. Interestingly binding to GAGs, did not simply rely on a net charge effect, but rather on more discrete saccharide features, such as 6-O-sulfation, or iduronic acid content. Using molecular modelling simulations, we proposed a model of Langerin/heparin complex, which located the GAG binding site at the interface of two of the three Carbohydrate-recognition domains of the protein, at the edge of the a-helix coiled-coil. To our knowledge, the binding properties that we have highlighted here for Langerin, have never been reported for C-type lectins before. These findings provide new insights towards the understanding of Langerin biological functions.

  9. On the Purpose of Event-B Proof Obligations

    DEFF Research Database (Denmark)

    Hallerstede, Stefan

    2011-01-01

    Event-B is a formal modelling method which is claimed to be suitable for diverse modelling domains, such as reactive systems and sequential program development. This claim hinges on the fact that any particular model has an appropriate semantics. In Event-B this semantics is provided implicitly b...

  10. 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.

  11. Two-Dimensional Micro-/Nanoradian Angle Generator with High Resolution and Repeatability Based on Piezo-Driven Double-Axis Flexure Hinge and Three Capacitive Sensors

    Directory of Open Access Journals (Sweden)

    Xinran Tan

    2017-11-01

    Full Text Available This study presents a two-dimensional micro-/nanoradian angle generator (2D-MNAG that achieves high angular displacement resolution and repeatability using a piezo-driven flexure hinge for two-dimensional deflections and three capacitive sensors for output angle monitoring and feedback control. The principal error of the capacitive sensor for precision microangle measurement is analyzed and compensated for; so as to achieve a high angle output resolution of 10 nrad (0.002 arcsec and positioning repeatability of 120 nrad (0.024 arcsec over a large angular range of ±4363 μrad (±900 arcsec for the 2D-MNAG. The impact of each error component, together with the synthetic error of the 2D-MNAG after principal error compensation are determined using Monte Carlo simulation for further improvement of the 2D-MNAG.

  12. A LigA three-domain region protects hamsters from lethal infection by Leptospira interrogans.

    Directory of Open Access Journals (Sweden)

    Mariana L Coutinho

    2011-12-01

    Full Text Available The leptospiral LigA protein consists of 13 bacterial immunoglobulin-like (Big domains and is the only purified recombinant subunit vaccine that has been demonstrated to protect against lethal challenge by a clinical isolate of Leptospira interrogans in the hamster model of leptospirosis. We determined the minimum number and location of LigA domains required for immunoprotection. Immunization with domains 11 and 12 was found to be required but insufficient for protection. Inclusion of a third domain, either 10 or 13, was required for 100% survival after intraperitoneal challenge with Leptospira interrogans serovar Copenhageni strain Fiocruz L1-130. As in previous studies, survivors had renal colonization; here, we quantitated the leptospiral burden by qPCR to be 1.2×10(3 to 8×10(5 copies of leptospiral DNA per microgram of kidney DNA. Although renal histopathology in survivors revealed tubulointerstitial changes indicating an inflammatory response to the infection, blood chemistry analysis indicated that renal function was normal. These studies define the Big domains of LigA that account for its vaccine efficacy and highlight the need for additional strategies to achieve sterilizing immunity to protect the mammalian host from leptospiral infection and its consequences.

  13. Switch control pocket inhibitors of p38-MAP kinase. Durable type II inhibitors that do not require binding into the canonical ATP hinge region.

    Science.gov (United States)

    Ahn, Yu Mi; Clare, Michael; Ensinger, Carol L; Hood, Molly M; Lord, John W; Lu, Wei-Ping; Miller, David F; Patt, William C; Smith, Bryan D; Vogeti, Lakshminarayana; Kaufman, Michael D; Petillo, Peter A; Wise, Scott C; Abendroth, Jan; Chun, Lawrence; Clark, Robin; Feese, Michael; Kim, Hidong; Stewart, Lance; Flynn, Daniel L

    2010-10-01

    Switch control pocket inhibitors of p38-alpha kinase are described. Durable type II inhibitors were designed which bind to arginines (Arg67 or Arg70) that function as key residues for mediating phospho-threonine 180 dependant conformational fluxing of p38-alpha from an inactive type II state to an active type I state. Binding to Arg70 in particular led to potent inhibitors, exemplified by DP-802, which also exhibited high kinase selectivity. Binding to Arg70 obviated the requirement for binding into the ATP Hinge region. X-ray crystallography revealed that DP-802 and analogs induce an enhanced type II conformation upon binding to either the unphosphorylated or the doubly phosphorylated form of p38-alpha kinase. Copyright © 2010 Elsevier Ltd. All rights reserved.

  14. Introduction and pinning of domain walls in 50 nm NiFe constrictions using local and external magnetic fields

    International Nuclear Information System (INIS)

    Zahnd, G.; Pham, V.T.; Marty, A.; Jamet, M.; Beigné, C.; Notin, L.; Vergnaud, C.; Rortais, F.; Vila, L.; Attané, J.-P.

    2016-01-01

    We study domain wall injection in 100 nm wide NiFe nanowires, followed by domain wall propagation and pinning on 50 nm wide constrictions. The injection is performed using local and external magnetic fields. Using several nucleation pad geometries, we show that at these small dimensions the use of an external field only does not allow obtaining a reproducible injection/pinning process. However, the use of an additional local field, created by an Oersted line, allows to nucleate a reversed domain at zero external applied field. Then, an external field of 5 mT enables the domain wall to propagate far from the Oersted line, and the pinning occurs reproducibly. We also show that notwithstanding the reproducibility of the pinning process, the depinning field is found to be stochastic, following a bimodal distribution. Using micromagnetic simulation we link two different DW configurations, vortex and transverse, to the two typical depinning fields. - Highlights: • Magnetic domain wall introduction and pinning in Permalloy nanowires with 50 nm wide constrictions. • Magnetic domain nucleation at zero external applied field. • Bimodal distribution of the domain wall configuration in the constriction.

  15. 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...

  16. The three domains of value: Why IL practitioners must take a holistic approach

    Directory of Open Access Journals (Sweden)

    Andrew Whitworth

    2010-09-01

    Full Text Available Many definitions of IL focus on the subjective value of information - the learner expected to be the initiator, agent and evaluator of an information search. However, we must also judge information against the objective domain: without it, we risk what Damian Thompson has called ‘counterknowledge’, the spread of unscientific worldviews like conspiracy theories, pseudohistory and so on. There is also the intersubjective domain, the field of laws, morals, economics and community standards. Without this domain we may collapse into relativism. But the subjective domain remains valuable, as otherwise we would suffer from ‘groupthink’, becoming merely the instrument of organisations and ‘the system’. All three domains of value are thus essential if the informational resources on which we draw are to be sustainable, healthy and open, and if we are to respond to the challenges posed by diversity and highlighted by this conference. Why, then, is so little IL teaching thinking about its subject in this way? I suggest the answers lie in how governments and other influential educational stakeholders conceive of their ‘product’. Not every educational stakeholder wants to see the kind of critical, creative thinkers which holistic IL is oriented to producing. Addressing this paradox is a significant policy challenge facing IL as it matures in the 21st century.

  17. Magnetic domains and magnetic stability of cohenite from the Morasko iron meteorite

    Energy Technology Data Exchange (ETDEWEB)

    Reznik, B. [Institute of Applied Geosciences, Karlsruhe Institute of Technology, Karlsruhe (Germany); Kontny, A., E-mail: agnes.kontny@kit.edu [Institute of Applied Geosciences, Karlsruhe Institute of Technology, Karlsruhe (Germany); Uehara, M.; Gattacceca, J. [CNRS, Aix Marseille Univ, IRD, Coll France, CEREGE, Aix-en-Provence (France); Solheid, P.; Jackson, M. [Institute for Rock Magnetism, University of Minnesota, Minneapolis, MN (United States)

    2017-03-15

    Magnetic properties, texture and microstructure of cohenite grains from Morasko iron meteorite have been investigated using electron backscattered diffraction, Bitter pattern technique, magneto-optical imaging method and magnetic force microscopy. Cohenite shows much stronger magnetic contrast compared to kamacite because it is magnetically harder than the Fe-Ni alloy, and thus causes higher stray fields. A surprising result is the high stability and reversibility of the global stripe-like magnetic domain structure in cohenite when applying high magnetic fields up to 1.5 T, and exposing it to high temperatures above the Curie temperature of about 220 °C. Heating up to 700 °C under atmosphere conditions has shown that cohenite remains stable and that the global magnetic domain structures mainly recover to its preheating state. This observation suggests that magnetic domains are strongly controlled by the crystal anisotropy of cohenite. Branching magnetic domain structures at the grain boundary to kamacite can be annealed, which indicates that they are very sensitive to record deformation. EBSD observations clearly demonstrate that increasing deviation from the easy [010] crystallographic axis and stress localization are the main factors controlling the distortion of Bitter patterns, and suggest a high sensitivity of the cohenite magnetic domain structure to local microstructural heterogeneities. The results of this study substantiate the theory that cohenite can be a good recorder of magnetic fields in planetary core material. - Highlights: • Magnetic domain structure of cohenite from the Morasko iron meteorite was investigated by Bitter pattern method, magneto-optical imaging and magnetic force microscopy. • Strong magnetocrystalline anisotropy explains high magnetic stability. • Magnetic domain structure shows high sensitivity to local microstructural heterogeneities. • Cohenite is probably a good recorder of magnetic fields in planetary core material.

  18. Magnetic domains and magnetic stability of cohenite from the Morasko iron meteorite

    International Nuclear Information System (INIS)

    Reznik, B.; Kontny, A.; Uehara, M.; Gattacceca, J.; Solheid, P.; Jackson, M.

    2017-01-01

    Magnetic properties, texture and microstructure of cohenite grains from Morasko iron meteorite have been investigated using electron backscattered diffraction, Bitter pattern technique, magneto-optical imaging method and magnetic force microscopy. Cohenite shows much stronger magnetic contrast compared to kamacite because it is magnetically harder than the Fe-Ni alloy, and thus causes higher stray fields. A surprising result is the high stability and reversibility of the global stripe-like magnetic domain structure in cohenite when applying high magnetic fields up to 1.5 T, and exposing it to high temperatures above the Curie temperature of about 220 °C. Heating up to 700 °C under atmosphere conditions has shown that cohenite remains stable and that the global magnetic domain structures mainly recover to its preheating state. This observation suggests that magnetic domains are strongly controlled by the crystal anisotropy of cohenite. Branching magnetic domain structures at the grain boundary to kamacite can be annealed, which indicates that they are very sensitive to record deformation. EBSD observations clearly demonstrate that increasing deviation from the easy [010] crystallographic axis and stress localization are the main factors controlling the distortion of Bitter patterns, and suggest a high sensitivity of the cohenite magnetic domain structure to local microstructural heterogeneities. The results of this study substantiate the theory that cohenite can be a good recorder of magnetic fields in planetary core material. - Highlights: • Magnetic domain structure of cohenite from the Morasko iron meteorite was investigated by Bitter pattern method, magneto-optical imaging and magnetic force microscopy. • Strong magnetocrystalline anisotropy explains high magnetic stability. • Magnetic domain structure shows high sensitivity to local microstructural heterogeneities. • Cohenite is probably a good recorder of magnetic fields in planetary core material.

  19. Domain wall propagation tuning in magnetic nanowires through geometric modulation

    Energy Technology Data Exchange (ETDEWEB)

    Arzuza, L.C.C., E-mail: luisarzuza179@gmail.com [Instituto de Física Gleb Wataghin, Universidade Estadual de Campinas, 13083-859 Campinas (SP) (Brazil); Universidad de la Costa, Departamento de Ciencias Naturales y Exactas, Calle 58 No. 55-66, Barranquilla (Colombia); López-Ruiz, R. [Instituto de Física Gleb Wataghin, Universidade Estadual de Campinas, 13083-859 Campinas (SP) (Brazil); Salazar-Aravena, D. [Instituto de Física Gleb Wataghin, Universidade Estadual de Campinas, 13083-859 Campinas (SP) (Brazil); Departamento de Física, Facultad de Ciencias, Universidad de Tarapacá, 1000007 Arica (Chile); Knobel, M. [Instituto de Física Gleb Wataghin, Universidade Estadual de Campinas, 13083-859 Campinas (SP) (Brazil); Brazilian Nanotechnology National Laboratory, Centro Nacional de Pesquisa em Energia e Materiais (CNPEM), 13083-970 Campinas (SP) (Brazil); Béron, F.; Pirota, K.R. [Instituto de Física Gleb Wataghin, Universidade Estadual de Campinas, 13083-859 Campinas (SP) (Brazil)

    2017-06-15

    Highlights: • The modulated nanowires dynamics occurs through two reversal modes. • Modulated nanowires show a change in the χ in contrast to homogeneous ones. • The FORC method reveals a non-uniform stray field due to shape modulation. - Abstract: The magnetic behavior of nickel modulated nanowires embedded in porous alumina membranes is investigated. Their diameters exhibit a sharp transition between below (35 nm) and above (52 nm) the theoretical limit for transverse and vortex domain walls. Magnetic hysteresis loops and first-order reversal curves (FORCs) were measured on several ordered nanowire arrays with different wide-narrow segment lengths ratio and compared with those from homogenous nanowires. The experimental magnetic response evidences a rather complex susceptibility behavior for nanowires with modulated diameter. Micromagnetic simulations on isolated and first-neighbors arrays of nanowires show that the domain wall structure, which depends on the segment diameter, suffers a transformation while crossing the diameter modulation, but without any pinning. The experimental array magnetic behavior can be ascribed to a heterogeneous stray field induced by the diameter modulation, yielding a stronger interaction field at the wide extremity than at the narrow one. The results evidence the possibility to control the domain wall propagation and morphology by modulating the lateral aspect of the magnetic entity.

  20. PREFACE: Domain wall dynamics in nanostructures Domain wall dynamics in nanostructures

    Science.gov (United States)

    Marrows, C. H.; Meier, G.

    2012-01-01

    Domain structures in magnetic materials are ubiquitous and have been studied for decades. The walls that separate them are topological defects in the magnetic order parameter and have a wide variety of complex forms. In general, their investigation is difficult in bulk materials since only the domain structure on the surface of a specimen is visible. Cutting the sample to reveal the interior causes a rearrangement of the domains into a new form. As with many other areas of magnetism, the study of domain wall physics has been revitalised by the advent of nanotechnology. The ability to fabricate nanoscale structures has permitted the formation of simplified and controlled domain patterns; the development of advanced microscopy methods has permitted them to be imaged and then modelled; subjecting them to ultrashort field and current pulses has permitted their dynamics to be explored. The latest results from all of these advances are described in this special issue. Not only has this led to results of great scientific beauty, but also to concepts of great applicability to future information technologies. In this issue the reader will find the latest results for these domain wall dynamics and the high-speed processes of topological structures such as domain walls and magnetic vortices. These dynamics can be driven by the application of magnetic fields, or by flowing currents through spintronic devices using the novel physics of spin-transfer torque. This complexity has been studied using a wide variety of experimental techniques at the edge of the spatial and temporal resolution currently available, and can be described using sophisticated analytical theory and computational modelling. As a result, the dynamics can be engineered to give rise to finely controlled memory and logic devices with new functionality. Moreover, the field is moving to study not only the conventional transition metal ferromagnets, but also complex heterostructures, novel magnets and even other

  1. Time-domain modeling of electromagnetic diffusion with a frequency-domain code

    NARCIS (Netherlands)

    Mulder, W.A.; Wirianto, M.; Slob, E.C.

    2007-01-01

    We modeled time-domain EM measurements of induction currents for marine and land applications with a frequency-domain code. An analysis of the computational complexity of a number of numerical methods shows that frequency-domain modeling followed by a Fourier transform is an attractive choice if a

  2. Nonlinear time-domain soil–structure interaction analysis of embedded reactor structures subjected to earthquake loads

    Energy Technology Data Exchange (ETDEWEB)

    Solberg, Jerome M., E-mail: solberg2@llnl.gov [Methods Development Group, Lawrence Livermore Nat’l Lab, P.O. Box 808, Mailstop L-125, Livermore, CA 94550 (United States); Hossain, Quazi, E-mail: hossain1@llnl.gov [Structural and Applied Mechanics Group, Lawrence Livermore Nat’l Lab, P.O. Box 808, Mailstop L-129, Livermore, CA 94550 (United States); Mseis, George, E-mail: george.mseis@gmail.com [Structural and Applied Mechanics Group, Lawrence Livermore Nat’l Lab, P.O. Box 808, Mailstop L-129, Livermore, CA 94550 (United States)

    2016-08-01

    Highlights: • Derived modified version of Bielak’s SSI method for nonlinear time-domain analysis. • Utilized a Ramberg–Osgood material with parameters that can be fit to EPRI data. • Matched vertically propagating shear wave results from CARES. • Applied this technique to a representative SMR, compared well with SASSI. • The technique is extensible to other material models and nonlinear effects. - Abstract: A generalized time-domain method for soil–structure interaction analysis is developed, based upon an extension of the work of the domain reduction method of Bielak et al. The methodology is combined with the use of a simple hysteretic soil model based upon the Ramberg–Osgood formulation and applied to a notional Small Modular Reactor. These benchmark results compare well (with some caveats) with those obtained by using the industry-standard frequency-domain code SASSI. The methodology provides a path forward for investigation of other sources of nonlinearity, including those associated with the use of more physically-realistic material models incorporating pore-pressure effects, gap opening/closing, the effect of nonlinear structural elements, and 3D seismic inputs.

  3. The effects of glutamine/asparagine content on aggregation and heterologous prion induction by yeast prion-like domains.

    Science.gov (United States)

    Shattuck, Jenifer E; Waechter, Aubrey C; Ross, Eric D

    2017-07-04

    Prion-like domains are low complexity, intrinsically disordered domains that compositionally resemble yeast prion domains. Many prion-like domains are involved in the formation of either functional or pathogenic protein aggregates. These aggregates range from highly dynamic liquid droplets to highly ordered detergent-insoluble amyloid-like aggregates. To better understand the amino acid sequence features that promote conversion to stable, detergent-insoluble aggregates, we used the prediction algorithm PAPA to identify predicted aggregation-prone prion-like domains with a range of compositions. While almost all of the predicted aggregation-prone domains formed foci when expressed in cells, the ability to form the detergent-insoluble aggregates was highly correlated with glutamine/asparagine (Q/N) content, suggesting that high Q/N content may specifically promote conversion to the amyloid state in vivo. We then used this data set to examine cross-seeding between prion-like proteins. The prion protein Sup35 requires the presence of a second prion, [PIN + ], to efficiently form prions, but this requirement can be circumvented by the expression of various Q/N-rich protein fragments. Interestingly, almost all of the Q/N-rich domains that formed SDS-insoluble aggregates were able to promote prion formation by Sup35, highlighting the highly promiscuous nature of these interactions.

  4. Itk tyrosine kinase substrate docking is mediated by a nonclassical SH2 domain surface of PLCgamma1.

    Science.gov (United States)

    Min, Lie; Joseph, Raji E; Fulton, D Bruce; Andreotti, Amy H

    2009-12-15

    Interleukin-2 tyrosine kinase (Itk) is a Tec family tyrosine kinase that mediates signaling processes after T cell receptor engagement. Activation of Itk requires recruitment to the membrane via its pleckstrin homology domain, phosphorylation of Itk by the Src kinase, Lck, and binding of Itk to the SLP-76/LAT adapter complex. After activation, Itk phosphorylates and activates phospholipase C-gamma1 (PLC-gamma1), leading to production of two second messengers, DAG and IP(3). We have previously shown that phosphorylation of PLC-gamma1 by Itk requires a direct, phosphotyrosine-independent interaction between the Src homology 2 (SH2) domain of PLC-gamma1 and the kinase domain of Itk. We now define this docking interface using a combination of mutagenesis and NMR spectroscopy and show that disruption of the Itk/PLCgamma1 docking interaction attenuates T cell signaling. The binding surface on PLCgamma1 that mediates recognition by Itk highlights a nonclassical binding activity of the well-studied SH2 domain providing further evidence that SH2 domains participate in important signaling interactions beyond recognition of phosphotyrosine.

  5. LOADS INTERACTION DOMAINS METHODOLOGY FOR THE DESIGN OF STEEL GREENHOUSE STRUCTURES

    Directory of Open Access Journals (Sweden)

    Sergio Castellano

    2007-03-01

    Full Text Available Aim of this research is to develop a design methodology which correlates main structural design parameters, whose production is characterised by high levels of standardization, such as the height of gutter or the distance between frames, with actions on the greenhouse. The methodology, based on the use of charts and abacus, permits a clear and a direct interpretation of the structural response to design load combinations and allows the design of structural improvements with the aim of the optimization of the ratio benefits (structural strength/costs. The study of structural interaction domains allowed a clear and a direct interpretation of the structural response to design load combinations. The diagrams highlight not only if the structure fulfils the standard requirements but also the safety levels with respect to design load combinations and allow the structural designer how to operate in order to optimize the structural response with standard requirements achieving the best ratio benefits (structural safety/ costs. The methodology was developed basing on criteria assigned by EN13031 on two different kinds of greenhouse structures: an arched greenhouse with a film plastic covering and a duo pitched roof greenhouse cover with rigid plastic membranes. Structural interaction domains for arched greenhouse showed a better capability of the structure to resist to vertical loads then to horizontal one. Moreover, the climatic load distribution on the structure assigned by EN13031 is such that the combination of climatic actions is less dangerous for the structure then their individual application. Whilst, duo pitched roof steel greenhouse interaction domains, showed a better capability of the structure to resist to vertical loads then to horizontal one and that, in any case, the serviceability limit states analysis is more strict then the ULS one. The shape of structural domains highlighted that the combination of actions is more dangerous for the

  6. 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.

  7. Separated matter and antimatter domains with vanishing domain walls

    Energy Technology Data Exchange (ETDEWEB)

    Dolgov, A.D.; Godunov, S.I.; Rudenko, A.S.; Tkachev, I.I., E-mail: dolgov@fe.infn.it, E-mail: sgodunov@itep.ru, E-mail: a.s.rudenko@inp.nsk.su, E-mail: tkachev@ms2.inr.ac.ru [Physics Department and Laboratory of Cosmology and Elementary Particle Physics, Novosibirsk State University, Pirogova st. 2, Novosibirsk, 630090 (Russian Federation)

    2015-10-01

    We present a model of spontaneous (or dynamical) C and CP violation where it is possible to generate domains of matter and antimatter separated by cosmologically large distances. Such C(CP) violation existed only in the early universe and later it disappeared with the only trace of generated baryonic and/or antibaryonic domains. So the problem of domain walls in this model does not exist. These features are achieved through a postulated form of interaction between inflaton and a new scalar field, realizing short time C(CP) violation.

  8. The structure of a conserved Piezo channel domain reveals a novel beta sandwich fold

    Science.gov (United States)

    Kamajaya, Aron; Kaiser, Jens; Lee, Jonas; Reid, Michelle; Rees, Douglas C.

    2014-01-01

    Summary Piezo has recently been identified as a family of eukaryotic mechanosensitive channels composed of subunits containing over 2000 amino acids, without recognizable sequence similarity to other channels. Here, we present the crystal structure of a large, conserved extramembrane domain located just before the last predicted transmembrane helix of C. elegans PIEZO, which adopts a novel beta sandwich fold. The structure was also determined of a point mutation located on a conserved surface at the position equivalent to the human PIEZO1 mutation found in Dehydrated Hereditary Stomatocytosis (DHS) patients (M2225R). While the point mutation does not change the overall domain structure, it does alter the surface electrostatic potential that may perturb interactions with a yet-to-be identified ligand or protein. The lack of structural similarity between this domain and any previously characterized fold, including those of eukaryotic and bacterial channels, highlights the distinctive nature of the Piezo family of eukaryotic mechanosensitive channels. PMID:25242456

  9. Axonal Membranes and Their Domains: Assembly and Function of the Axon Initial Segment and Node of Ranvier

    Directory of Open Access Journals (Sweden)

    Andrew D. Nelson

    2017-05-01

    Full Text Available Neurons are highly specialized cells of the nervous system that receive, process and transmit electrical signals critical for normal brain function. Here, we review the intricate organization of axonal membrane domains that facilitate rapid action potential conduction underlying communication between complex neuronal circuits. Two critical excitable domains of vertebrate axons are the axon initial segment (AIS and the nodes of Ranvier, which are characterized by the high concentrations of voltage-gated ion channels, cell adhesion molecules and specialized cytoskeletal networks. The AIS is located at the proximal region of the axon and serves as the site of action potential initiation, while nodes of Ranvier, gaps between adjacent myelin sheaths, allow rapid propagation of the action potential through saltatory conduction. The AIS and nodes of Ranvier are assembled by ankyrins, spectrins and their associated binding partners through the clustering of membrane proteins and connection to the underlying cytoskeleton network. Although the AIS and nodes of Ranvier share similar protein composition, their mechanisms of assembly are strikingly different. Here we will cover the mechanisms of formation and maintenance of these axonal excitable membrane domains, specifically highlighting the similarities and differences between them. We will also discuss recent advances in super resolution fluorescence imaging which have elucidated the arrangement of the submembranous axonal cytoskeleton revealing a surprising structural organization necessary to maintain axonal organization and function. Finally, human mutations in axonal domain components have been associated with a growing number of neurological disorders including severe cognitive dysfunction, epilepsy, autism, neurodegenerative diseases and psychiatric disorders. Overall, this review highlights the assembly, maintenance and function of axonal excitable domains, particularly the AIS and nodes of

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

    International Nuclear Information System (INIS)

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

    2014-01-01

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

  11. Probing Protein Multidimensional Conformational Fluctuations by Single-Molecule Multiparameter Photon Stamping Spectroscopy

    Science.gov (United States)

    2015-01-01

    Conformational motions of proteins are highly dynamic and intrinsically complex. To capture the temporal and spatial complexity of conformational motions and further to understand their roles in protein functions, an attempt is made to probe multidimensional conformational dynamics of proteins besides the typical one-dimensional FRET coordinate or the projected conformational motions on the one-dimensional FRET coordinate. T4 lysozyme hinge-bending motions between two domains along α-helix have been probed by single-molecule FRET. Nevertheless, the domain motions of T4 lysozyme are rather complex involving multiple coupled nuclear coordinates and most likely contain motions besides hinge-bending. It is highly likely that the multiple dimensional protein conformational motions beyond the typical enzymatic hinged-bending motions have profound impact on overall enzymatic functions. In this report, we have developed a single-molecule multiparameter photon stamping spectroscopy integrating fluorescence anisotropy, FRET, and fluorescence lifetime. This spectroscopic approach enables simultaneous observations of both FRET-related site-to-site conformational dynamics and molecular rotational (or orientational) motions of individual Cy3-Cy5 labeled T4 lysozyme molecules. We have further observed wide-distributed rotational flexibility along orientation coordinates by recording fluorescence anisotropy and simultaneously identified multiple intermediate conformational states along FRET coordinate by monitoring time-dependent donor lifetime, presenting a whole picture of multidimensional conformational dynamics in the process of T4 lysozyme open-close hinge-bending enzymatic turnover motions under enzymatic reaction conditions. By analyzing the autocorrelation functions of both lifetime and anisotropy trajectories, we have also observed the dynamic and static inhomogeneity of T4 lysozyme multidimensional conformational fluctuation dynamics, providing a fundamental

  12. A small molecule fusion inhibitor of dengue virus

    NARCIS (Netherlands)

    Poh, Mee Kian; Yip, Andy; Zhang, Summer; Priestle, John P.; Ma, Ngai Ling; Smit, Jolanda M.; Wischut, Jan; Shi, Pei-Yong; Wenk, Markus R.; Schul, Wouter

    2009-01-01

    The dengue virus envelope protein plays an essential role in viral entry by mediating fusion between the viral and host membranes. The crystal structure of the envelope protein shows a pocket (located at a "hinge" between Domains I and II) that can be occupied by ligand n-octyl-beta-D-glucoside

  13. Identifying the Role of E2 Domains on Alphavirus Neutralization and Protective Immune Responses.

    Directory of Open Access Journals (Sweden)

    James Weger-Lucarelli

    Full Text Available Chikungunya virus (CHIKV and other alphaviruses are the etiologic agents of numerous diseases in both humans and animals. Despite this, the viral mediators of protective immunity against alphaviruses are poorly understood, highlighted by the lack of a licensed human vaccine for any member of this virus genus. The alphavirus E2, the receptor-binding envelope protein, is considered to be the predominant target of the protective host immune response. Although envelope protein domains have been studied for vaccine and neutralization in flaviviruses, their role in alphaviruses is less characterized. Here, we describe the role of the alphavirus E2 domains in neutralization and protection through the use of chimeric viruses.Four chimeric viruses were constructed in which individual E2 domains of CHIKV were replaced with the corresponding domain from Semliki Forest virus (SFV (ΔDomA/ΔDomB/ΔDomC/ ΔDomA+B. Vaccination studies in mice (both live and inactivated virus revealed that domain B was the primary determinant of neutralization. Neutralization studies with CHIKV immune serum from humans were consistent with mouse studies, as ΔDomB was poorly neutralized.Using chimeric viruses, it was determined that the alphavirus E2 domain B was the critical target of neutralizing antibodies in both mice and humans. Therefore, chimeric viruses may have more relevance for vaccine discovery than peptide-based approaches, which only detect linear epitopes. This study provides new insight into the role of alphavirus E2 domains on neutralization determinants and may be useful for the design of novel therapeutic technologies.

  14. BARC highlights '88

    International Nuclear Information System (INIS)

    1989-01-01

    Highlights of research and development activities of the Bhabha Atomic Research Centre (BARC), Bombay during 1988 are presented in chapters entitled: Physical Sciences, Chemical Sciences, Materials and Materials Sciences, Radioisotopes, Reactors, Fuel Cycle, Radiological Safety and Protection, Electronics and Instrumentation, Engineering Services, and Life Sciences. Main thrust of the R and D activities of BARC is on nuclear power reactor technology and all stages of nuclear fuel cycle. Some activities are also in the frontier areas such as high temperature superconductivity and inertial confinement fusion. (M.G.B.). figs., tabs., coloured ills

  15. Strain-controlled magnetic domain wall propagation in hybrid piezoelectric/ferromagnetic structures.

    Science.gov (United States)

    Lei, Na; Devolder, Thibaut; Agnus, Guillaume; Aubert, Pascal; Daniel, Laurent; Kim, Joo-Von; Zhao, Weisheng; Trypiniotis, Theodossis; Cowburn, Russell P; Chappert, Claude; Ravelosona, Dafiné; Lecoeur, Philippe

    2013-01-01

    The control of magnetic order in nanoscale devices underpins many proposals for integrating spintronics concepts into conventional electronics. A key challenge lies in finding an energy-efficient means of control, as power dissipation remains an important factor limiting future miniaturization of integrated circuits. One promising approach involves magnetoelectric coupling in magnetostrictive/piezoelectric systems, where induced strains can bear directly on the magnetic anisotropy. While such processes have been demonstrated in several multiferroic heterostructures, the incorporation of such complex materials into practical geometries has been lacking. Here we demonstrate the possibility of generating sizeable anisotropy changes, through induced strains driven by applied electric fields, in hybrid piezoelectric/spin-valve nanowires. By combining magneto-optical Kerr effect and magnetoresistance measurements, we show that domain wall propagation fields can be doubled under locally applied strains. These results highlight the prospect of constructing low-power domain wall gates for magnetic logic devices.

  16. Functional analysis of the NH{sub 2}-terminal hydrophobic region and BRICHOS domain of GKN1

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Jung Hwan; Choi, Yoo Jin; Choi, Won Suk; Nam, Suk Woo; Lee, Jung Young; Park, Won Sang, E-mail: wonsang@catholic.ac.kr

    2013-11-01

    Highlights: •NH{sub 2}-terminal and BRICHOS domain of GKN1 inhibited tumor cell growth. •NH{sub 2}-terminal and BRICHOS domain of GKN1 regulated cell cycle. •NH{sub 2}-terminal and BRICHOS domain of GKN1 inhibited epigenetic regulators. -- Abstract: Gastrokine 1 (GKN1) protects the gastric antral mucosa and promotes healing by facilitating restitution and proliferation after injury. GKN1 is down-regulated in Helicobacter pylori-infected gastric epithelial cells and loss of GKN1 expression is tightly associated with gastric carcinogenesis. However, the underlying mechanisms as a tumor suppressor are largely unknown. Presently, the hydrophobic region and BRICHOS domain of GKN1, pGKN1{sup D13N}, pGKN1{sup Δ68–199}, and pGKN1{sup Δ1–67,165–199} were shown to suppress gastric cancer cell growth and recapitulate GKN1 functions. As well, the hydrophobic region and BRICHOS domain of GKN1 had a synergistic anti-cancer effect with 5-FU on tumor cell growth, implying that the NH{sub 2}-terminal hydrophobic region and BRICHOS domain of GKN1 are sufficient for tumor suppression, thereby suggesting a therapeutic intervention for gastric cancer. Also, its domain inducing endogenous miR-185 directly targeted the epigenetic effectors DNMT1 and EZH2 in gastric cancer cells. Our results suggest that the NH{sub 2}-terminal hydrophobic region and BRICHOS domain of GKN1 are sufficient for its tumor suppressor activities.

  17. Integrating hinge axis approximation and the virtual facial simulation of prosthetic outcomes for treatment with CAD-CAM immediate dentures: A clinical report of a patient with microstomia.

    Science.gov (United States)

    Kuric, Katelyn M; Harris, Bryan T; Morton, Dean; Azevedo, Bruno; Lin, Wei-Shao

    2017-09-29

    This clinical report describes a digital workflow using extraoral digital photographs and volumetric datasets from cone beam computed tomography (CBCT) imaging to create a 3-dimensional (3D), virtual patient with photorealistic appearance. In a patient with microstomia, hinge axis approximation, diagnostic casts simulating postextraction alveolar ridge profile, and facial simulation of prosthetic treatment outcome were completed in a 3D, virtual environment. The approach facilitated the diagnosis, communication, and patient acceptance of the treatment of maxillary and mandibular computer-aided design and computer-aided manufacturing (CAD-CAM) of immediate dentures at increased occlusal vertical dimension. Copyright © 2017 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

  18. Domain Walls and Matter-Antimatter Domains in the Early Universe

    Directory of Open Access Journals (Sweden)

    Dolgov A.D.

    2017-01-01

    Full Text Available We suggest a scenario of spontaneous (or dynamical C and CP violation according to which it is possible to generate domains of matter and antimatter separated by cosmologically large distances. Such C(CP violation existed only in the early universe and later it disappeared with the only trace of generated matter and antimatter domains. So this scenario does not suffer from the problem of domain walls. According to this scenario the width of the domain wall should grow exponentially to prevent annihilation at the domain boundaries. Though there is a classical result obtained by Basu and Vilenkin that the width of the wall tends to the one of the stationary solution (constant physical width. That is why we considered thick domain walls in a de Sitter universe following paper by Basu and Vilenkin. However, we were interested not only in stationary solutions found therein, but also investigated the general case of domain wall evolution with time. When the wall thickness parameter, δ0 , is smaller than H−1/2 where H is the Hubble parameter in de Sitter space-time, then the stationary solutions exist, and initial field configurations tend with time to the stationary ones. However, there are no stationary solutions for δ0>H−1/2 We have calculated numerically the rate of the wall expansion in this case and have found that the width of the wall grows exponentially fast for δ0≫H−1 An explanation for the critical value δ0c=H−1/2 is also proposed.

  19. Ferroelectric domains and phase evolution in (Fe:) KTa{sub 1−x}Nb{sub x}O{sub 3} crystals

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Hongyang; Cai, Kang; Fan, Ziran; Huang, Zhideng [Hubei Key Laboratory of Plasma Chemistry and Advanced Materials, Department of Materials Science and Engineering, Wuhan Institute of Technology, 693 Xiongchu Road, Wuhan 430073 (China); Ma, Zhibin, E-mail: mazb@wit.edu.cn [Hubei Key Laboratory of Plasma Chemistry and Advanced Materials, Department of Materials Science and Engineering, Wuhan Institute of Technology, 693 Xiongchu Road, Wuhan 430073 (China); Jia, Tingting; Kimura, Hideo [National Institute for Materials Science, Sengen 1-2-1, Tsukuba 305-0047 (Japan); Yang, Yuguo [New Materials Research Institute, Shandong Academy of Sciences, No. 19, Keyuan Road, Jinan 250014 (China); Matsumoto, Takao; Tohei, Tetsuya; Shibata, Naoya; Ikuhara, Yuichi [Institute of Engineering Innovation, School of Engineering, University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-8656 (Japan)

    2017-08-15

    Highlights: • Three phase transitions were observed: the R–O, O–T, T–C evolutions. • KTN ferroelectric domain switching is because of the nano-polar-regions. • The domain evolution showed KTN has triangle shape, but Fe: KTN has straight line. - Abstract: The domain structures and phase evolution in mixed ferroelectric (Fe): KTa{sub 1−x}Nb{sub x}O{sub 3} (KTN) crystals were investigated. Temperature dependent Raman spectra show that Curie temperatures of KTN and Fe: KTN are far below room temperature, but the ferroelectric domain switching was still visualized by scanning probe microscopy at room temperature. These observed domains origin from the nano-regions near the grain boundaries. In addition, the intrinsic domains (triangle for KTN and straight line/stripe for Fe: KTN) could only be observed at low temperature by transmission electron microscopy. Three phase transitions in Fe: KTN crystals were found by Raman spectroscopy and dielectric testing: 175 K for Rhombohedral-to-Orthorhombic (R–O), 210 K for Orthorhombic-to-Tetragonal (O–T) and 250 K for Tetragonal-to-Cubic (T–C), which is consistent with the domain behavior.

  20. Domain configuration and magnetization switching in arrays of permalloy nanostripes

    International Nuclear Information System (INIS)

    Iglesias-Freire, Ó.; Jaafar, M.; Pérez, L.; Abril, O. de; Vázquez, M.; Asenjo, A.

    2014-01-01

    The proximity effect in the collective behavior of arrays of magnetic nanostripes is currently a subject of intensive research. The imperative of reducing the size and distances between elements in order to achieve higher storage capacity, faster access to the information as well as low energy consumption, brings consequences about the isolated behavior of the elements and devices. Parallel to each other permalloy nanostripes with high aspect ratio have been prepared by the nanolithography technique. The evolution of the closure domains and the magnetization direction in individual nanostructures has been imaged under applied magnetic fields using Variable Field Magnetic Force Microscopy. Moreover, the magnetostatic interactions between neighboring elements and the proximity effects in arrays of such nanostructures have been quantitatively analyzed by Magnetic Force Microscopy and micromagnetic simulations. The agreement between simulations and the experimental results allows us to conclude the relevance of those interactions depending on the geometry characteristics. In particular, results suggest that the magnetostatic coupling between adjacent nanostripes vanishes for separation distances higher than 500 nm. - Highlights: • A shape anisotropy-induced single domain remanent state is present in the stripes. Closure domains are formed under external fields. • Separation distances between neighboring stripes (500 nm) are enough to overcome the magnetostatic coupling and avoid a multi-stripe character. • Micromagnetic simulations predict critical distances of around 500 nm for the onset of magnetostatic coupling between neighboring elements. • Simulations predict stripes with a small longitudinal separation to behave as single elements, with domain walls “jumping” between them

  1. Domain configuration and magnetization switching in arrays of permalloy nanostripes

    Energy Technology Data Exchange (ETDEWEB)

    Iglesias-Freire, Ó., E-mail: aasenjo@icmm.csic.es [Instituto de Ciencia de Materiales de Madrid, CSIC, Sor Juana Inés de la Cruz 3, Madrid 28049 (Spain); Jaafar, M. [Instituto de Ciencia de Materiales de Madrid, CSIC, Sor Juana Inés de la Cruz 3, Madrid 28049 (Spain); Dpto. Física de la Materia Condensada, Universidad Autónoma de Madrid, Cantoblanco 28049 (Spain); Pérez, L. [Dpto. Física de Materiales, Universidad Complutense de Madrid, Madrid 28040 (Spain); Abril, O. de [Dpto. Física e Instalaciones Aplicadas a la Edificación, al Medio Ambiente y al Urbanismo, Universidad Politécnica de Madrid, Madrid 28040 (Spain); Vázquez, M.; Asenjo, A. [Instituto de Ciencia de Materiales de Madrid, CSIC, Sor Juana Inés de la Cruz 3, Madrid 28049 (Spain)

    2014-04-15

    The proximity effect in the collective behavior of arrays of magnetic nanostripes is currently a subject of intensive research. The imperative of reducing the size and distances between elements in order to achieve higher storage capacity, faster access to the information as well as low energy consumption, brings consequences about the isolated behavior of the elements and devices. Parallel to each other permalloy nanostripes with high aspect ratio have been prepared by the nanolithography technique. The evolution of the closure domains and the magnetization direction in individual nanostructures has been imaged under applied magnetic fields using Variable Field Magnetic Force Microscopy. Moreover, the magnetostatic interactions between neighboring elements and the proximity effects in arrays of such nanostructures have been quantitatively analyzed by Magnetic Force Microscopy and micromagnetic simulations. The agreement between simulations and the experimental results allows us to conclude the relevance of those interactions depending on the geometry characteristics. In particular, results suggest that the magnetostatic coupling between adjacent nanostripes vanishes for separation distances higher than 500 nm. - Highlights: • A shape anisotropy-induced single domain remanent state is present in the stripes. Closure domains are formed under external fields. • Separation distances between neighboring stripes (500 nm) are enough to overcome the magnetostatic coupling and avoid a multi-stripe character. • Micromagnetic simulations predict critical distances of around 500 nm for the onset of magnetostatic coupling between neighboring elements. • Simulations predict stripes with a small longitudinal separation to behave as single elements, with domain walls “jumping” between them.

  2. AEB-highlights. January - June 1977

    International Nuclear Information System (INIS)

    1977-01-01

    AEB Highlights is a half-yearly report reflecting the most important recent achievements of the various Research and Technical divisions of the Atomic Energy Board. It appears alternatively in English and Afrikaans [af

  3. IGC highlights 1988

    International Nuclear Information System (INIS)

    1989-01-01

    The major thrust of the research and development (R and D) activities of the Indira Gandhi Centre for Atomic Research (IGCAR), Kalpakkam is oriented towards mastering fast breeder reactor (FBR) technology. Towards this end, its current R and D activities are carried out in a wide variety of disciplines. Highlights of its R and D activities during 1988 are summarised under the headings: Reactor Engineering and Design, Reactor Physics and Safety, Materials Science and Technology, Sodium Chemistry and Technology, Fuel Reprocessing and Electronics and Instrumentation. The text is illustrated with a number of figures, graphs and coloured pictures. (M.G.B.). figs., tabs

  4. Molecular dynamics simulation reveals insights into the mechanism of unfolding by the A130T/V mutations within the MID1 zinc-binding Bbox1 domain.

    Directory of Open Access Journals (Sweden)

    Yunjie Zhao

    Full Text Available The zinc-binding Bbox1 domain in protein MID1, a member of the TRIM family of proteins, facilitates the ubiquitination of the catalytic subunit of protein phosphatase 2A and alpha4, a protein regulator of PP2A. The natural mutation of residue A130 to a valine or threonine disrupts substrate recognition and catalysis. While NMR data revealed the A130T mutant Bbox1 domain failed to coordinate both structurally essential zinc ions and resulted in an unfolded structure, the unfolding mechanism is unknown. Principle component analysis revealed that residue A130 served as a hinge point between the structured β-strand-turn-β-strand (β-turn-β and the lasso-like loop sub-structures that constitute loop1 of the ββα-RING fold that the Bbox1 domain adopts. Backbone RMSD data indicate significant flexibility and departure from the native structure within the first 5 ns of the molecular dynamics (MD simulation for the A130V mutant (>6 Å and after 30 ns for A130T mutant (>6 Å. Overall RMSF values were higher for the mutant structures and showed increased flexibility around residues 125 and 155, regions with zinc-coordinating residues. Simulated pKa values of the sulfhydryl group of C142 located near A130 suggested an increased in value to ~9.0, paralleling the increase in the apparent dielectric constants for the small cavity near residue A130. Protonation of the sulfhydryl group would disrupt zinc-coordination, directly contributing to unfolding of the Bbox1. Together, the increased motion of residues of loop 1, which contains four of the six zinc-binding cysteine residues, and the increased pKa of C142 could destabilize the structure of the zinc-coordinating residues and contribute to the unfolding.

  5. 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.

  6. Energy Policy. Highlights. 2013 Edition

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2013-07-01

    Energy Policy Highlights showcases recent developments in energy policies among all 28 IEA member countries. Each contribution underscores the changing nature of both global and domestic energy challenges, as well as the commonality of energy concerns among member countries. The policies highlighted in this publication identify an urgent need to reduce greenhouse gas (GHG) emissions as a clear policy objective. Electricity, enhancing energy efficiency and increasing the share of renewables in the energy mix in a cost effective manner are likewise areas of common focus. On the end-user side, increasing public awareness of domestic energy policies through improved transparency and engagement is an important facet of policy support among IEA member countries. The successful implementation of policies and other initiatives benefitted from efforts to inform the public.

  7. Megabase replication domains along the human genome: relation to chromatin structure and genome organisation.

    Science.gov (United States)

    Audit, Benjamin; Zaghloul, Lamia; Baker, Antoine; Arneodo, Alain; Chen, Chun-Long; d'Aubenton-Carafa, Yves; Thermes, Claude

    2013-01-01

    In higher eukaryotes, the absence of specific sequence motifs, marking the origins of replication has been a serious hindrance to the understanding of (i) the mechanisms that regulate the spatio-temporal replication program, and (ii) the links between origins activation, chromatin structure and transcription. In this chapter, we review the partitioning of the human genome into megabased-size replication domains delineated as N-shaped motifs in the strand compositional asymmetry profiles. They collectively span 28.3% of the genome and are bordered by more than 1,000 putative replication origins. We recapitulate the comparison of this partition of the human genome with high-resolution experimental data that confirms that replication domain borders are likely to be preferential replication initiation zones in the germline. In addition, we highlight the specific distribution of experimental and numerical chromatin marks along replication domains. Domain borders correspond to particular open chromatin regions, possibly encoded in the DNA sequence, and around which replication and transcription are highly coordinated. These regions also present a high evolutionary breakpoint density, suggesting that susceptibility to breakage might be linked to local open chromatin fiber state. Altogether, this chapter presents a compartmentalization of the human genome into replication domains that are landmarks of the human genome organization and are likely to play a key role in genome dynamics during evolution and in pathological situations.

  8. The 15-Minute Audition: Translating a Proof of Concept into a Domain-Specific Screening Device for Mathematical Talent

    Science.gov (United States)

    Subotnik, Rena F.; Worrell, Frank C.; Olszewski-Kubilius, Paula

    2017-01-01

    In 2011, Subotnik, Olszewski-Kubilius, and Worrell proposed a conceptual model for talent development applicable to all domains. Although grounded in available psychological research, significant questions remain regarding practical applications of each tenet of the model. In this article, we highlight a method of implementing the model's focus on…

  9. Analysis of domain wall dynamics based on skewness of magnetic Barkhausen noise for applied stress determination

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Song [College of Electrical Engineering and Control Science, Nanjing Tech University, Nanjing, Jiangsu 211816 (China); School of Automation Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, Jiangsu 210016 (China); Tian, GuiYun, E-mail: tian280@hotmail.com [School of Automation Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, Jiangsu 210016 (China); School of Electrical and Electronic Engineering, Merz Court, University of Newcastle upon Tyne, Newcastle NE1 7RU (United Kingdom); Dobmann, Gerd; Wang, Ping [School of Automation Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, Jiangsu 210016 (China)

    2017-01-01

    Skewness of Magnetic Barkhausen Noise (MBN) signal is used as a new feature for applied stress determination. After experimental studies, skewness presents its ability for measuring applied tensile stress compared with conventional feature, meanwhile, a non-linear behavior of this new feature and an independence of the excitation conditions under compressive stress are found and discussed. Effective damping during domain wall motion influencing the asymmetric shape of the MBN statistical distribution function is discussed under compressive and tensile stress variation. Domain wall (DW) energy and distance between pinning edges of the DW are considered altering the characteristic relaxation time, which is the reason for the non-linear phenomenon of skewness. - Highlights: • The skewness of magnetic Barkhausen noise profile is proposed as a new feature for applied stress determination. • The skewness is sensitive to applied stress and independent to excitation frequency. • Domain wall energy and pinning distance influence the relaxation time of domain wall, which leads to a non-linear behavior of skewness under compressive stress.

  10. Reconfigurable magnonic crystal consisting of periodically distributed domain walls in a nanostrip

    International Nuclear Information System (INIS)

    Li, Zhi-xiong; Wang, Xi-guang; Wang, Dao-wei; Nie, Yao-zhuang; Tang, Wei; Guo, Guang-hua

    2015-01-01

    We study spin wave propagation in a new type of magnonic crystal consisting of a series of periodically distributed magnetic domain walls in a nanostrip by micromagnetic simulation. Spin wave bands and bandgaps are observed in frequency spectra and dispersion curves. Some bandgaps are caused by the Bragg reflection of the spin wave modes at the Brillouin zone boundaries, while others originate from the coupling between different incident and reflected spin wave modes. The control of the spin wave band structure by changing the magnetocrystalline anisotropy or applying an external magnetic field is studied. Increasing the magnetocrystalline anisotropy leads to an increase of the bandgaps. The external field applied perpendicular to the nanostrip gives rise to a doubling of the domain-wall magnonic crystal period. As a result, more bandgaps appear on the frequency spectra of propagating spin waves. The results presented here may find their use in the design of reconfigurable magnonic devices. - Highlights: • A reconfigurable magnonic crystal consisting of domain walls in a uniform nanostrip is proposed. • Propagating characteristics of spin waves in such magnonic crystal are studied. • Spin-wave band structures can be effectively manipulated by magnetic anisotropy or magnetic field

  11. Domain Decomposition Solvers for Frequency-Domain Finite Element Equations

    KAUST Repository

    Copeland, Dylan

    2010-10-05

    The paper is devoted to fast iterative solvers for frequency-domain finite element equations approximating linear and nonlinear parabolic initial boundary value problems with time-harmonic excitations. Switching from the time domain to the frequency domain allows us to replace the expensive time-integration procedure by the solution of a simple linear elliptic system for the amplitudes belonging to the sine- and to the cosine-excitation or a large nonlinear elliptic system for the Fourier coefficients in the linear and nonlinear case, respectively. The fast solution of the corresponding linear and nonlinear system of finite element equations is crucial for the competitiveness of this method. © 2011 Springer-Verlag Berlin Heidelberg.

  12. Domain Decomposition Solvers for Frequency-Domain Finite Element Equations

    KAUST Repository

    Copeland, Dylan; Kolmbauer, Michael; Langer, Ulrich

    2010-01-01

    The paper is devoted to fast iterative solvers for frequency-domain finite element equations approximating linear and nonlinear parabolic initial boundary value problems with time-harmonic excitations. Switching from the time domain to the frequency domain allows us to replace the expensive time-integration procedure by the solution of a simple linear elliptic system for the amplitudes belonging to the sine- and to the cosine-excitation or a large nonlinear elliptic system for the Fourier coefficients in the linear and nonlinear case, respectively. The fast solution of the corresponding linear and nonlinear system of finite element equations is crucial for the competitiveness of this method. © 2011 Springer-Verlag Berlin Heidelberg.

  13. Domain shape instabilities and dendrite domain growth in uniaxial ferroelectrics

    Science.gov (United States)

    Shur, Vladimir Ya.; Akhmatkhanov, Andrey R.

    2018-01-01

    The effects of domain wall shape instabilities and the formation of nanodomains in front of moving walls obtained in various uniaxial ferroelectrics are discussed. Special attention is paid to the formation of self-assembled nanoscale and dendrite domain structures under highly non-equilibrium switching conditions. All obtained results are considered in the framework of the unified kinetic approach to domain structure evolution based on the analogy with first-order phase transformation. This article is part of the theme issue `From atomistic interfaces to dendritic patterns'.

  14. Effect of domain variations on damping capacity of Fe-16Cr-2.5Mo alloy solution annealed at 1373 K and 1473 K

    International Nuclear Information System (INIS)

    Xu Yonggang; Ning Li; Wen Yuhua

    2011-01-01

    The damping capacity of Fe-16Cr-2.5Mo alloy heat-treated at different temperatures was investigated. A water-based magnetic fluid was used to analyze domain morphologies. The experimental results show that there is a maximum value of damping capacity when the solution annealing temperature of the material is 1373 K. When the annealing temperature is higher, the damping capacity of the alloy drops quickly. The change in damping capacity with the solution annealing temperature is believed to be due to different domain morphologies. The domains are larger and the domain-wall area is smaller in the alloy annealed at a higher temperature. The wedge-shaped domains acted as obstacles for pinning the domain-wall movement, even though movement of the 90 o domains is easy. As a result, the damping capacity of the alloys drops when the annealing temperature is very high. - Research Highlights: →The change in damping capacity with solution annealing temperature is believed to be due to different domain morphologies. →The domains are larger and the domain-wall area is smaller in the alloy annealed at a higher temperature. →The wedge-shaped domains acted as obstacles for pinning the domain-wall movement, even though movement of the 90 o domains is easy.

  15. The structure of a conserved piezo channel domain reveals a topologically distinct β sandwich fold.

    Science.gov (United States)

    Kamajaya, Aron; Kaiser, Jens T; Lee, Jonas; Reid, Michelle; Rees, Douglas C

    2014-10-07

    Piezo has recently been identified as a family of eukaryotic mechanosensitive channels composed of subunits containing over 2,000 amino acids, without recognizable sequence similarity to other channels. Here, we present the crystal structure of a large, conserved extramembrane domain located just before the last predicted transmembrane helix of C. elegans PIEZO, which adopts a topologically distinct β sandwich fold. The structure was also determined of a point mutation located on a conserved surface at the position equivalent to the human PIEZO1 mutation found in dehydrated hereditary stomatocytosis patients (M2225R). While the point mutation does not change the overall domain structure, it does alter the surface electrostatic potential that may perturb interactions with a yet-to-be-identified ligand or protein. The lack of structural similarity between this domain and any previously characterized fold, including those of eukaryotic and bacterial channels, highlights the distinctive nature of the Piezo family of eukaryotic mechanosensitive channels. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Lead bioaccessibility in topsoils from lead mineralisation and urban domains, UK

    International Nuclear Information System (INIS)

    Appleton, J.D.; Cave, M.R.; Palumbo-Roe, B.; Wragg, J.

    2013-01-01

    Predictive linear regression (LR) modelling indicates that total Pb is the only highly significant independent variable for estimating Pb bioaccessibility in “mineralisation domains” located in limestone (high pH) and partly peat covered (low pH) shale-sandstone terrains in England. Manganese is a significant minor predictor in the limestone terrain, whilst organic matter and sulphur explain 0.5% and 2% of the variance of bioaccessible Pb in the peat-shale-sandstone terrain, compared with 93% explained by total Pb. Bootstrap resampling shows that LR confidence limits overlap for the two mineralised terrains but the limestone terrain has a significantly lower bioaccessible Pb to total Pb slope than the urban domain. A comparison of the absolute values of stomach and combined stomach-intestine bioaccessibility provides some insight into the geochemical controls on bioaccessibility in the contrasting soil types. -- Highlights: •Total Pb is the only highly significant predictor for bioaccessible Pb in lead mineralisation domains. •Manganese is a significant minor predictor in limestone terrain. •Organic matter and sulphur are minor predictors in peat-shale-sandstone terrain. •Results can be used for initial risk assessment in Pb mineralisation domain. -- Total Pb is the major predictor for bioaccessible Pb in topsoils from two lead mineralised areas in England

  17. Three-dimensional reconstructions of the bacteriophage CUS-3 virion reveal a conserved coat protein I-domain but a distinct tailspike receptor-binding domain

    International Nuclear Information System (INIS)

    Parent, Kristin N.; Tang, Jinghua; Cardone, Giovanni; Gilcrease, Eddie B.; Janssen, Mandy E.; Olson, Norman H.; Casjens, Sherwood R.; Baker, Timothy S.

    2014-01-01

    CUS-3 is a short-tailed, dsDNA bacteriophage that infects serotype K1 Escherichia coli. We report icosahedrally averaged and asymmetric, three-dimensional, cryo-electron microscopic reconstructions of the CUS-3 virion. Its coat protein structure adopts the “HK97-fold” shared by other tailed phages and is quite similar to that in phages P22 and Sf6 despite only weak amino acid sequence similarity. In addition, these coat proteins share a unique extra external domain (“I-domain”), suggesting that the group of P22-like phages has evolved over a very long time period without acquiring a new coat protein gene from another phage group. On the other hand, the morphology of the CUS-3 tailspike differs significantly from that of P22 or Sf6, but is similar to the tailspike of phage K1F, a member of the extremely distantly related T7 group of phages. We conclude that CUS-3 obtained its tailspike gene from a distantly related phage quite recently. - Highlights: • Asymmetric and symmetric three-dimensional reconstructions of phage CUS-3 are presented. • CUS-3 major capsid protein has a conserved I-domain, which is found in all three categories of “P22-like phage”. • CUS-3 has very different tailspike receptor binding domain from those of P22 and Sf6. • The CUS-3 tailspike likely was acquired by horizontal gene transfer

  18. Three-dimensional reconstructions of the bacteriophage CUS-3 virion reveal a conserved coat protein I-domain but a distinct tailspike receptor-binding domain

    Energy Technology Data Exchange (ETDEWEB)

    Parent, Kristin N., E-mail: kparent@msu.edu [Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093-0378 (United States); Tang, Jinghua; Cardone, Giovanni [Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093-0378 (United States); Gilcrease, Eddie B. [University of Utah School of Medicine, Division of Microbiology and Immunology, Department of Pathology, Salt Lake City, UT 84112 (United States); Janssen, Mandy E.; Olson, Norman H. [Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093-0378 (United States); Casjens, Sherwood R., E-mail: sherwood.casjens@path.utah.edu [University of Utah School of Medicine, Division of Microbiology and Immunology, Department of Pathology, Salt Lake City, UT 84112 (United States); Baker, Timothy S., E-mail: tsb@ucsd.edu [Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093-0378 (United States); University of California, San Diego, Division of Biological Sciences, La Jolla, CA, 92093 (United States)

    2014-09-15

    CUS-3 is a short-tailed, dsDNA bacteriophage that infects serotype K1 Escherichia coli. We report icosahedrally averaged and asymmetric, three-dimensional, cryo-electron microscopic reconstructions of the CUS-3 virion. Its coat protein structure adopts the “HK97-fold” shared by other tailed phages and is quite similar to that in phages P22 and Sf6 despite only weak amino acid sequence similarity. In addition, these coat proteins share a unique extra external domain (“I-domain”), suggesting that the group of P22-like phages has evolved over a very long time period without acquiring a new coat protein gene from another phage group. On the other hand, the morphology of the CUS-3 tailspike differs significantly from that of P22 or Sf6, but is similar to the tailspike of phage K1F, a member of the extremely distantly related T7 group of phages. We conclude that CUS-3 obtained its tailspike gene from a distantly related phage quite recently. - Highlights: • Asymmetric and symmetric three-dimensional reconstructions of phage CUS-3 are presented. • CUS-3 major capsid protein has a conserved I-domain, which is found in all three categories of “P22-like phage”. • CUS-3 has very different tailspike receptor binding domain from those of P22 and Sf6. • The CUS-3 tailspike likely was acquired by horizontal gene transfer.

  19. 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

  20. The extended-domain-eigenfunction method for solving elliptic boundary value problems with annular domains

    Energy Technology Data Exchange (ETDEWEB)

    Aarao, J; Bradshaw-Hajek, B H; Miklavcic, S J; Ward, D A, E-mail: Stan.Miklavcic@unisa.edu.a [School of Mathematics and Statistics, University of South Australia, Mawson Lakes, SA 5095 (Australia)

    2010-05-07

    Standard analytical solutions to elliptic boundary value problems on asymmetric domains are rarely, if ever, obtainable. In this paper, we propose a solution technique wherein we embed the original domain into one with simple boundaries where the classical eigenfunction solution approach can be used. The solution in the larger domain, when restricted to the original domain, is then the solution of the original boundary value problem. We call this the extended-domain-eigenfunction method. To illustrate the method's strength and scope, we apply it to Laplace's equation on an annular-like domain.

  1. 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.

  2. 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

  3. Highlights of nuclear chemistry 1995

    International Nuclear Information System (INIS)

    1996-07-01

    In this report 9 topics of the work of the Nuclear Chemistry Group in 1995 are highlighted. A list of publications and an overview of the international cooperation is given. (orig.). 19 refs., 19 figs., 2 tabs., 2 app

  4. Highlights of nuclear chemistry 1995

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-07-01

    In this report 9 topics of the work of the Nuclear Chemistry Group in 1995 are highlighted. A list of publications and an overview of the international cooperation is given. (orig.). 19 refs., 19 figs., 2 tabs., 2 app.

  5. LAMA Preconference and Program Highlights.

    Science.gov (United States)

    Library Administration & Management, 1988

    1988-01-01

    Highlights events of the Library Administration and Management Association 1988 conference, including presentation of awards and programs on: (1) transfer of training; (2) hiring; (3) mentoring; (4) acquisitions automation; (5) library building consultation; and (6) managing shared systems. (MES)

  6. 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.

  7. 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.

  8. Signatures of pleiotropy, economy and convergent evolution in a domain-resolved map of human-virus protein-protein interaction networks.

    Science.gov (United States)

    Garamszegi, Sara; Franzosa, Eric A; Xia, Yu

    2013-01-01

    A central challenge in host-pathogen systems biology is the elucidation of general, systems-level principles that distinguish host-pathogen interactions from within-host interactions. Current analyses of host-pathogen and within-host protein-protein interaction networks are largely limited by their resolution, treating proteins as nodes and interactions as edges. Here, we construct a domain-resolved map of human-virus and within-human protein-protein interaction networks by annotating protein interactions with high-coverage, high-accuracy, domain-centric interaction mechanisms: (1) domain-domain interactions, in which a domain in one protein binds to a domain in a second protein, and (2) domain-motif interactions, in which a domain in one protein binds to a short, linear peptide motif in a second protein. Analysis of these domain-resolved networks reveals, for the first time, significant mechanistic differences between virus-human and within-human interactions at the resolution of single domains. While human proteins tend to compete with each other for domain binding sites by means of sequence similarity, viral proteins tend to compete with human proteins for domain binding sites in the absence of sequence similarity. Independent of their previously established preference for targeting human protein hubs, viral proteins also preferentially target human proteins containing linear motif-binding domains. Compared to human proteins, viral proteins participate in more domain-motif interactions, target more unique linear motif-binding domains per residue, and contain more unique linear motifs per residue. Together, these results suggest that viruses surmount genome size constraints by convergently evolving multiple short linear motifs in order to effectively mimic, hijack, and manipulate complex host processes for their survival. Our domain-resolved analyses reveal unique signatures of pleiotropy, economy, and convergent evolution in viral-host interactions that are

  9. Translating Comprehensive Conservative Care for Chronic Knee Pain Into a Digital Care Pathway: 12-Week and 6-Month Outcomes for the Hinge Health Program

    Science.gov (United States)

    Erhart-Hledik, Jennifer C; Kinsella, Rose; Hunter, Simon; Mecklenburg, Gabriel; Perez, Daniel

    2017-01-01

    Background Chronic knee pain (CKP) affects a large number of adults, many of whom do not receive best-practice care and are at high risk for unnecessary surgery. Objective The aim of this study was to investigate the effect of the Hinge Health 12-week digital care program (DCP) for CKP on knee pain and function, with secondary outcomes of surgery interest and satisfaction, at 12 weeks and 6 months after starting the program. Methods Individuals with CKP were recruited onto the 12-week program, comprising sensor-guided physical exercises, weekly education, activity tracking, and psychosocial support such as personal coaching and cognitive behavioral therapy (CBT). We used a single-arm design with assessment of outcomes at baseline, 12 weeks, and 6 months after starting the program. We used a linear mixed effects model with Tukey contrasts to compare timepoints and report intention-to-treat statistics with last observation carried forward. Results The cohort consisted of 41 individuals (32 female, mean age 52 years, SD 9 years). Between baseline and week 12, participants reported clinically significant improvements in the Knee Injury and Osteoarthritis Outcome Score (KOOS) pain and Knee Injury and Osteoarthritis Outcome Score-Physical Function Short Form (KOOS-PS) function scales of 16 points (95% CI 12-21, P<.001) and 10 points (95% CI 6-14, P<.001), respectively. Significant reductions of 57% (mean difference 30, 95% CI 21-38, P<.001) and 51% (mean difference 25, 95% CI 16-33, P<.001) in visual analog scale (VAS) knee pain and stiffness, respectively, were observed at 12 weeks, as well as a 67% reduction in surgery interest (mean reduction 2.3 out of 10, 95% CI 1.5-3.1, P<.001). Average satisfaction at week 12 was 9.2 out of 10. Critically, all improvements were maintained at 6 months at similar or greater magnitude. Conclusions Participants on the Hinge Health DCP for CKP showed substantial clinical improvements that were maintained 6 months after enrolling in the

  10. Interoperable domain models : The ISO land administration domain model LADM and its external classes

    NARCIS (Netherlands)

    Lemmen, C.H.J.; Van Oosterom, P.J.M.; Uitermark, H.T.; Zevenbergen, J.A.; Cooper, A.K.

    2011-01-01

    This paper provides a brief overview of one of the first spatial domain standards: a standard for the domain of Land Administration (LA). This standard is in the draft stage of development now (May 2011). The development of domain standards is a logical follow up after domain-independent standards,

  11. Safety Culture Assessment Tools in Nuclear and Non-Nuclear Domains

    International Nuclear Information System (INIS)

    Mkrtchyan, L.; Turcanu, C.

    2012-01-01

    Over the last decades, in many domains especially in high risk industries, the authorities paid increasing attention to safety management systems and, in particular, to safety culture. Consequently, in the applied and academic literature a huge amount of studies explored the main challenges, issues and obstacles related with safety culture. We undertake a survey of safety culture experiences in the main safety-critical industries such as nuclear, railways, offshore, aviation, airlines, health care, etc. We review both academic and applied literature up to the year 2011. Our results help to establish a comprehensive view on the subject, its main terminologies, existing tools, and main difficulties. The purpose of this report is to raise awareness about the current tools of safety culture assessment, both in the nuclear as well as in the non-nuclear domain. The report provides also practical recommendations about the possible use of each tool given different circumstances and different factors. We do not aim to rank the tools pointing the best one, but we highlight instead the unique features of these tools, pointing their strong and weak sides

  12. Nanomagnetic domains of chromium deposited on vertically-aligned carbon nanotubes

    International Nuclear Information System (INIS)

    Wright, Andrew C.; Faulkner, Michael K.; Harris, Robert C.; Goddard, Alex; Abbott, Andrew P.

    2012-01-01

    The drive to create ever smaller magnetic memory devices has led to the development of new nanomagnetic domains on surfaces. This paper reports the development of nano-chromium magnetic domains obtained using electrodeposition on vertically aligned carbon nanofibers arrays. Attempts to achieve this using conventional aqueous solutions were unsuccessful even after thin nickel underlayers were applied. The use of a novel electrolyte, a deep eutectic solvent, made from choline chloride: chromium (III) chloride enabled highly conformal overcoatings of chromium on individual bare carbon nanotubes to be obtained. Very high aspect ratio metal microstructures could be obtained by this novel technology. Magnetic imaging of the coated nanoarrays showed there to be clear magnetic character to the coating when the thin coatings were applied but this disappeared when the deposits were thicker and more contiguous. - Highlights: ► Nanoscale chromium deposited from non-aqueous electrolyte shows magnetic behavior. ► Vertically aligned carbon nanotubes conformally coated with chromium metal. ► Ionic liquid electrolyte superior to chromic acid for plating high aspect ratio structures.

  13. Nanomagnetic domains of chromium deposited on vertically-aligned carbon nanotubes

    Energy Technology Data Exchange (ETDEWEB)

    Wright, Andrew C., E-mail: a.wright@glyndwr.ac.uk [Advanced Materials Research Laboratory, Materials Science Research Center, Glyndwr University, Wrexham LL11 2AW (United Kingdom); Faulkner, Michael K., E-mail: m.faulkner@manchester.ac.uk [Manchester Materials Science Centre, University of Manchester, Grosvenor Street, Manchester M13 9PL (United Kingdom); Harris, Robert C.; Goddard, Alex; Abbott, Andrew P., E-mail: apa1@le.ac.uk [Department of Chemistry, University of Leicester, Leicester LE1 7RH (United Kingdom)

    2012-12-15

    The drive to create ever smaller magnetic memory devices has led to the development of new nanomagnetic domains on surfaces. This paper reports the development of nano-chromium magnetic domains obtained using electrodeposition on vertically aligned carbon nanofibers arrays. Attempts to achieve this using conventional aqueous solutions were unsuccessful even after thin nickel underlayers were applied. The use of a novel electrolyte, a deep eutectic solvent, made from choline chloride: chromium (III) chloride enabled highly conformal overcoatings of chromium on individual bare carbon nanotubes to be obtained. Very high aspect ratio metal microstructures could be obtained by this novel technology. Magnetic imaging of the coated nanoarrays showed there to be clear magnetic character to the coating when the thin coatings were applied but this disappeared when the deposits were thicker and more contiguous. - Highlights: Black-Right-Pointing-Pointer Nanoscale chromium deposited from non-aqueous electrolyte shows magnetic behavior. Black-Right-Pointing-Pointer Vertically aligned carbon nanotubes conformally coated with chromium metal. Black-Right-Pointing-Pointer Ionic liquid electrolyte superior to chromic acid for plating high aspect ratio structures.

  14. Safety Culture Assessment Tools in Nuclear and Non-Nuclear Domains

    Energy Technology Data Exchange (ETDEWEB)

    Mkrtchyan, L; Turcanu, C

    2012-03-15

    Over the last decades, in many domains especially in high risk industries, the authorities paid increasing attention to safety management systems and, in particular, to safety culture. Consequently, in the applied and academic literature a huge amount of studies explored the main challenges, issues and obstacles related with safety culture. We undertake a survey of safety culture experiences in the main safety-critical industries such as nuclear, railways, offshore, aviation, airlines, health care, etc. We review both academic and applied literature up to the year 2011. Our results help to establish a comprehensive view on the subject, its main terminologies, existing tools, and main difficulties. The purpose of this report is to raise awareness about the current tools of safety culture assessment, both in the nuclear as well as in the non-nuclear domain. The report provides also practical recommendations about the possible use of each tool given different circumstances and different factors. We do not aim to rank the tools pointing the best one, but we highlight instead the unique features of these tools, pointing their strong and weak sides.

  15. Amino acid sequence requirements in the hinge of human immunoglobulin A1 (IgA1) for cleavage by streptococcal IgA1 proteases

    DEFF Research Database (Denmark)

    Batten, MR; Senior, BW; Kilian, Mogens

    2003-01-01

    The amino acid sequence requirements in the hinge of human immunoglobulin A1 (IgA1) for cleavage by IgA1 proteases of different species of Streptococcus were investigated. Recombinant IgA1 antibodies were generated with point mutations at proline 227 and threonine 228, the residues lying on either...... side of the peptide bond at which all streptococcal IgA1 proteases cleave wild-type human IgA1. The amino acid substitutions produced no major effect upon the structure of the mutant IgA1 antibodies or their functional ability to bind to Fcalpha receptors. However, the substitutions had a substantial...... effect upon sensitivity to cleavage with some streptococcal IgA1 proteases, with, in some cases, a single point mutation rendering the antibody resistant to a particular IgA1 protease. This effect was least marked with the IgA1 protease from Streptococcus pneumoniae, which showed no absolute requirement...

  16. High-resolution crystal structure reveals a HEPN domain at the C-terminal region of S. cerevisiae RNA endonuclease Swt1

    International Nuclear Information System (INIS)

    Peng, Shuxia; Zhou, Ke; Wang, Wenjia; Gao, Zengqiang; Dong, Yuhui; Liu, Quansheng

    2014-01-01

    Highlights: • Crystal structure of the C-terminal (CT) domain of Swt1 was determined at 2.3 Å. • Structure of the CT domain was identified as HEPN domain superfamily member. • Low-resolution envelope of Swt1 full-length in solution was analyzed by SAXS. • The middle and CT domains gave good fit to SAXS structural model. - Abstract: Swt1 is an RNA endonuclease that plays an important role in quality control of nuclear messenger ribonucleoprotein particles (mRNPs) in eukaryotes; however, its structural details remain to be elucidated. Here, we report the crystal structure of the C-terminal (CT) domain of Swt1 from Saccharomyces cerevisiae, which shares common characteristics of higher eukaryotes and prokaryotes nucleotide binding (HEPN) domain superfamily. To study in detail the full-length protein structure, we analyzed the low-resolution architecture of Swt1 in solution using small angle X-ray scattering (SAXS) method. Both the CT domain and middle domain exhibited a good fit upon superimposing onto the molecular envelope of Swt1. Our study provides the necessary structural information for detailed analysis of the functional role of Swt1, and its importance in the process of nuclear mRNP surveillance

  17. 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

  18. An Adaptor Domain-Mediated Auto-Catalytic Interfacial Kinase Reaction

    Science.gov (United States)

    Liao, Xiaoli; Su, Jing; Mrksich, Milan

    2010-01-01

    This paper describes a model system for studying the auto-catalytic phosphorylation of an immobilized substrate by a kinase enzyme. This work uses self-assembled monolayers (SAMs) of alkanethiolates on gold to present the peptide substrate on a planar surface. Treatment of the monolayer with Abl kinase results in phosphorylation of the substrate. The phosphorylated peptide then serves as a ligand for the SH2 adaptor domain of the kinase and thereby directs the kinase activity to nearby peptide substrates. This directed reaction is intramolecular and proceeds with a faster rate than does the initial, intermolecular reaction, making this an auto-catalytic process. The kinetic non-linearity gives rise to properties that have no counterpart in the corresponding homogeneous phase reaction: in one example, the rate for phosphorylation of a mixture of two peptides is faster than the sum of the rates for phosphorylation of each peptide when presented alone. This work highlights the use of an adaptor domain in modulating the activity of a kinase enzyme for an immobilized substrate and offers a new approach for studying biochemical reactions in spatially inhomogeneous settings. PMID:19821459

  19. A Review of Domain Modelling and Domain Imaging Techniques in Ferroelectric Crystals

    Directory of Open Access Journals (Sweden)

    John E. Huber

    2011-02-01

    Full Text Available The present paper reviews models of domain structure in ferroelectric crystals, thin films and bulk materials. Common crystal structures in ferroelectric materials are described and the theory of compatible domain patterns is introduced. Applications to multi-rank laminates are presented. Alternative models employing phase-field and related techniques are reviewed. The paper then presents methods of observing ferroelectric domain structure, including optical, polarized light, scanning electron microscopy, X-ray and neutron diffraction, atomic force microscopy and piezo-force microscopy. Use of more than one technique for unambiguous identification of the domain structure is also described.

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

    Energy Technology Data Exchange (ETDEWEB)

    Yun, Ji-Hye [Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Lee, Won Kyung [Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Kim, Heeyoun [Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Kim, Eunhee; Cheong, Chaejoon [Magnetic Resonance Team, Korea Basic Science Institute (KBSI), Ochang, Chungbuk 363-883 (Korea, Republic of); Cho, Myeon Haeng [Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Lee, Weontae, E-mail: wlee@spin.yonsei.ac.kr [Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of)

    2014-09-26

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

  1. Peripartum depression and anxiety as an integrative cross domain target for psychiatric preventative measures.

    Science.gov (United States)

    Babb, Jessica A; Deligiannidis, Kristina M; Murgatroyd, Christopher A; Nephew, Benjamin C

    2015-01-01

    Exposure to high levels of early life stress has been identified as a potent risk factor for neurodevelopmental delays in infants, behavioral problems and autism in children, but also for several psychiatric illnesses in adulthood, such as depression, anxiety, autism, and posttraumatic stress disorder. Despite having robust adverse effects on both mother and infant, the pathophysiology of peripartum depression and anxiety are poorly understood. The objective of this review is to highlight the advantages of using an integrated approach addressing several behavioral domains in both animal and clinical studies of peripartum depression and anxiety. It is postulated that a greater focus on integrated cross domain studies will lead to advances in treatments and preventative measures for several disorders associated with peripartum depression and anxiety. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. MiDas: automatic extraction of a common domain of discourse in sleep medicine for multi-center data integration.

    Science.gov (United States)

    Sahoo, Satya S; Ogbuji, Chimezie; Luo, Lingyun; Dong, Xiao; Cui, Licong; Redline, Susan S; Zhang, Guo-Qiang

    2011-01-01

    Clinical studies often use data dictionaries with controlled sets of terms to facilitate data collection, limited interoperability and sharing at a local site. Multi-center retrospective clinical studies require that these data dictionaries, originating from individual participating centers, be harmonized in preparation for the integration of the corresponding clinical research data. Domain ontologies are often used to facilitate multi-center data integration by modeling terms from data dictionaries in a logic-based language, but interoperability among domain ontologies (using automated techniques) is an unresolved issue. Although many upper-level reference ontologies have been proposed to address this challenge, our experience in integrating multi-center sleep medicine data highlights the need for an upper level ontology that models a common set of terms at multiple-levels of abstraction, which is not covered by the existing upper-level ontologies. We introduce a methodology underpinned by a Minimal Domain of Discourse (MiDas) algorithm to automatically extract a minimal common domain of discourse (upper-domain ontology) from an existing domain ontology. Using the Multi-Modality, Multi-Resource Environment for Physiological and Clinical Research (Physio-MIMI) multi-center project in sleep medicine as a use case, we demonstrate the use of MiDas in extracting a minimal domain of discourse for sleep medicine, from Physio-MIMI's Sleep Domain Ontology (SDO). We then extend the resulting domain of discourse with terms from the data dictionary of the Sleep Heart and Health Study (SHHS) to validate MiDas. To illustrate the wider applicability of MiDas, we automatically extract the respective domains of discourse from 6 sample domain ontologies from the National Center for Biomedical Ontologies (NCBO) and the OBO Foundry.

  3. Chemical Shift Assignments of the C-terminal Eps15 Homology Domain-3 EH Domain*

    Science.gov (United States)

    Caplan, Steve; Sorgen, Paul L.

    2013-01-01

    The C-terminal Eps15 homology (EH) domain 3 (EHD3) belongs to a eukaryotic family of endocytic regulatory proteins and is involved in the recycling of various receptors from the early endosome to the endocytic recycling compartment or in retrograde transport from the endosomes to the Golgi. EH domains are highly conserved in the EHD family and function as protein-protein interaction units that bind to Asn-Pro-Phe (NPF) motif-containing proteins. The EH domain of EHD1 was the first C-terminal EH domain from the EHD family to be solved by NMR. The differences observed between this domain and proteins with N-terminal EH domains helped describe a mechanism for the differential binding of NPF-containing proteins. Here, structural studies were expanded to include the EHD3 EH domain. While the EHD1 and EHD3 EH domains are highly homologous, they have different protein partners. A comparison of these structures will help determine the selectivity in protein binding between the EHD family members and lead to a better understanding of their unique roles in endocytic regulation. PMID:23754701

  4. An Amphipathic Helix Directs Cellular Membrane Curvature Sensing and Function of the BAR Domain Protein PICK1.

    Science.gov (United States)

    Herlo, Rasmus; Lund, Viktor K; Lycas, Matthew D; Jansen, Anna M; Khelashvili, George; Andersen, Rita C; Bhatia, Vikram; Pedersen, Thomas S; Albornoz, Pedro B C; Johner, Niklaus; Ammendrup-Johnsen, Ina; Christensen, Nikolaj R; Erlendsson, Simon; Stoklund, Mikkel; Larsen, Jannik B; Weinstein, Harel; Kjærulff, Ole; Stamou, Dimitrios; Gether, Ulrik; Madsen, Kenneth L

    2018-05-15

    BAR domains are dimeric protein modules that sense, induce, and stabilize lipid membrane curvature. Here, we show that membrane curvature sensing (MCS) directs cellular localization and function of the BAR domain protein PICK1. In PICK1, and the homologous proteins ICA69 and arfaptin2, we identify an amphipathic helix N-terminal to the BAR domain that mediates MCS. Mutational disruption of the helix in PICK1 impaired MCS without affecting membrane binding per se. In insulin-producing INS-1E cells, super-resolution microscopy revealed that disruption of the helix selectively compromised PICK1 density on insulin granules of high curvature during their maturation. This was accompanied by reduced hormone storage in the INS-1E cells. In Drosophila, disruption of the helix compromised growth regulation. By demonstrating size-dependent binding on insulin granules, our finding highlights the function of MCS for BAR domain proteins in a biological context distinct from their function, e.g., at the plasma membrane during endocytosis. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  5. Magnetic vortex state and multi-domain pattern in electrodeposited hemispherical nanogranular nickel films

    International Nuclear Information System (INIS)

    Samardak, Alexander; Sukovatitsina, Ekaterina; Ognev, Alexey; Stebliy, Maksim; Davydenko, Alexander; Chebotkevich, Ludmila; Keun Kim, Young; Nasirpouri, Forough; Janjan, Seyed-Mehdi; Nasirpouri, Farzad

    2014-01-01

    Magnetic states of nickel nanogranular films were studied in two distinct structures of individual and agglomerated granules electrodeposited on n-type Si(1 1 1) surface from a modified Watts bath at a low pH of 2. Magnetic force microscopy and micromagnetic simulations revealed three-dimensional out-of-plane magnetic vortex states in stand-alone hemispherical granules and their arrays, and multi-domain patterns in large agglomerates and integrated films. Once the granules coalesce into small chains or clusters, the coercivity values increased due to the reduction of inter-granular spacing and strengthening of the magnetostatic interaction. Further growth leads to the formation of a continuous granulated film which strongly affected the coercivity and remanence. This was characterized by the domain wall nucleation and propagation leading to a stripe domain pattern. Magnetoresistance measurements as a function of external magnetic field are indicative of anisotropic magnetoresistance (AMR) for the continuous films electrodeposited on Si substrate. - Highlights: • Magnetic states of electrodeposited nickel in isolated spherical and agglomerated nanogranules, and a continuous film. • Preferential magnetization reversal mechanism in isolated granules is vortex state. • Micromagnetic simulations confirm the three-dimensional vortex. • Transition between the vortex state and multi-domain magnetic pattern causes a significant decrease in the coercive force. • Continuous nickel films electrodeposited on silicon substrate exhibit AMR whose magnitude increases with the film thickness

  6. Hierarchy and scaling behavior of multi-rank domain patterns in ferroelectric K0.9Na0.1NbO3 strained films

    Science.gov (United States)

    Braun, Dorothee; Schmidbauer, Martin; Hanke, Michael; Schwarzkopf, Jutta

    2018-01-01

    The formation process of a ferroelectric multi-rank domain pattern in the thickness range of 7-52 nm is investigated for monoclinic K0.9Na0.1NbO3 strained epitaxial films on (110) NdScO3 substrates. Although the elastic strain energy density is degenerated for two pseudocubic orientations, a distinctive hierarchy of domain evolution is observed with exclusive in-plane a1a2 domains for very thin films and the retarded onset of a ferroelectric MC phase at larger film thickness. This is accompanied by a thickness dependent transformation from stripe domains to a herringbone pattern and, eventually, for the thickest film, to a checkerboard-like structure. These transformations in the domain arrangement and width are correlated to energetic aspects as depolarization field and anisotropic strain relaxation in the film. While for the MC domains plastic strain relaxation is throughout observed, the a1a2 domains show a two-step strain relaxation mechanism starting with an in-plane elastic shearing, which is followed by plastic lattice relaxation. Our results highlight a pathway for engineering and patterning of periodic ferroelectric domain structures.

  7. The framing of scientific domains

    DEFF Research Database (Denmark)

    Dam Christensen, Hans

    2014-01-01

    domains, and UNISIST helps understanding this navigation. Design/methodology/approach The UNISIST models are tentatively applied to the domain of art history at three stages, respectively two modern, partially overlapping domains, as well as an outline of an art historical domain anno c1820...

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

    International Nuclear Information System (INIS)

    Öberg, Christine; Belikov, Sergey

    2012-01-01

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

  9. The wings of Bombyx mori develop from larval discs exhibiting an ...

    Indian Academy of Sciences (India)

    Unknown

    presumptive wing blade domains unlike in Drosophila, where it is confined to the hinge and the wing pouch. ... events are different and the wing discs behave like presumptive wing buds .... emerge with the fore- and the hind-wings (figure 1e, j) on ... phosis (compare c with d, and h with i) during the larval to pupal transition.

  10. 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

  11. 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

  12. Apo and ligand-bound structures of ModA from the archaeon Methanosarcina acetivorans

    International Nuclear Information System (INIS)

    Chan, Sum; Giuroiu, Iulia; Chernishof, Irina; Sawaya, Michael R.; Chiang, Janet; Gunsalus, Robert P.; Arbing, Mark A.; Perry, L. Jeanne

    2010-01-01

    Crystal structures of ModA from M. acetivorans in the apo and ligand-bound conformations confirm domain rotation upon ligand binding. The trace-element oxyanion molybdate, which is required for the growth of many bacterial and archaeal species, is transported into the cell by an ATP-binding cassette (ABC) transporter superfamily uptake system called ModABC. ModABC consists of the ModA periplasmic solute-binding protein, the integral membrane-transport protein ModB and the ATP-binding and hydrolysis cassette protein ModC. In this study, X-ray crystal structures of ModA from the archaeon Methanosarcina acetivorans (MaModA) have been determined in the apoprotein conformation at 1.95 and 1.69 Å resolution and in the molybdate-bound conformation at 2.25 and 2.45 Å resolution. The overall domain structure of MaModA is similar to other ModA proteins in that it has a bilobal structure in which two mixed α/β domains are linked by a hinge region. The apo MaModA is the first unliganded archaeal ModA structure to be determined: it exhibits a deep cleft between the two domains and confirms that upon binding ligand one domain is rotated towards the other by a hinge-bending motion, which is consistent with the ‘Venus flytrap’ model seen for bacterial-type periplasmic binding proteins. In contrast to the bacterial ModA structures, which have tetrahedral coordination of their metal substrates, molybdate-bound MaModA employs octahedral coordination of its substrate like other archaeal ModA proteins

  13. FY 2016 Research Highlights

    Energy Technology Data Exchange (ETDEWEB)

    2017-03-23

    This fact sheet summarizes the research highlights for the Clean Energy Manufacturing Analysis Center (CEMAC) for Fiscal Year 2106. Topics covered include additive manufacturing for the wind industry, biomass-based chemicals substitutions, carbon fiber manufacturing facility siting, geothermal power plant turbines, hydrogen refueling stations, hydropower turbines, LEDs and lighting, light-duty automotive lithium-ion cells, magnetocaloric refrigeration, silicon carbide power electronics for variable frequency motor drives, solar photovoltaics, and wide bandgap semiconductor opportunities in power electronics.

  14. Elucidating heterogeneity of IgA1 hinge-region O-glycosylation by use of MALDI-TOF/TOF mass spectrometry: role of cysteine alkylation during sample processing.

    Science.gov (United States)

    Franc, Vojtěch; Řehulka, Pavel; Raus, Martin; Stulík, Jiří; Novak, Jan; Renfrow, Matthew B; Šebela, Marek

    2013-10-30

    Determining disease-associated changes in protein glycosylation provides a better understanding of pathogenesis. This work focuses on human immunoglobulin A1 (IgA1), where aberrant O-glycosylation plays a key role in the pathogenesis of IgA nephropathy (IgAN). Normal IgA1 hinge region carries 3 to 6 O-glycans consisting of N-acetylgalactosamine (GalNAc) and galactose (Gal); both sugars may be sialylated. In IgAN patients, some O-glycans on a fraction of IgA1 molecules are Gal-deficient. Here we describe a sample preparation protocol with optimized cysteine alkylation of a Gal-deficient polymeric IgA1 myeloma protein prior to in-gel digestion and analysis of the digest by MALDI-TOF/TOF mass spectrometry (MS). Following a novel strategy, IgA1 hinge-region O-glycopeptides were fractionated by reversed-phase liquid chromatography using a microgradient device and identified by MALDI-TOF/TOF tandem MS (MS/MS). The acquired MS/MS spectra were interpreted manually and by means of our own software. This allowed assigning up to six O-glycosylation sites and demonstration, for the first time, of the distribution of isomeric O-glycoforms having the same molecular mass, but a different glycosylation pattern. The most abundant Gal-deficient O-glycoforms were GalNAc4Gal3 and GalNAc5Gal4 with one Gal-deficient site and GalNAc5Gal3 and GalNAc4Gal2 with two Gal-deficient sites. The most frequent Gal-deficient sites were at Ser230 and/or Thr236. In this work, we studied the O-glycosylation in the hinge region of human immunoglobulin A1 (IgA1). Aberrant glycosylation of the protein plays a key role in the pathogenesis of IgA nephropathy. Thus identification of the O-glycan composition of IgA1 is important for a deeper understanding of the disease mechanism, biomarker discovery and validation, and implementation and monitoring of disease-specific therapies. We developed a new procedure for elucidating the heterogeneity of IgA1 O-glycosylation. After running a polyacrylamide gel

  15. Secular trends on traditional ecological knowledge: An analysis of different domains of knowledge among Tsimane' men.

    Science.gov (United States)

    Reyes-García, Victoria; Luz, Ana C; Gueze, Maximilien; Paneque-Gálvez, Jaime; Macía, Manuel J; Orta-Martínez, Martí; Pino, Joan

    2013-10-01

    Empirical research provides contradictory evidence of the loss of traditional ecological knowledge across societies. Researchers have argued that culture, methodological differences, and site-specific conditions are responsible for such contradictory evidences. We advance and test a third explanation: the adaptive nature of traditional ecological knowledge systems. Specifically, we test whether different domains of traditional ecological knowledge experience different secular changes and analyze trends in the context of other changes in livelihoods. We use data collected among 651 Tsimane' men (Bolivian Amazon). Our findings indicate that different domains of knowledge follow different secular trends. Among the domains of knowledge analyzed, medicinal and wild edible knowledge appear as the most vulnerable; canoe building and firewood knowledge seem to remain constant across generations; whereas house building knowledge seems to experience a slight secular increase. Our analysis reflects on the adaptive nature of traditional ecological knowledge, highlighting how changes in this knowledge system respond to the particular needs of a society in a given point of time.

  16. LFA-1 and Mac-1 integrins bind to the serine/threonine-rich domain of thrombomodulin

    Energy Technology Data Exchange (ETDEWEB)

    Kawamoto, Eiji [Department of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507 (Japan); Emergency and Critical Care Center, Mie University Hospital, 2-174 Edobashi, Tsu 514-8507 (Japan); Okamoto, Takayuki, E-mail: okamotot@doc.medic.mie-u.ac.jp [Department of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507 (Japan); Takagi, Yoshimi [Department of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507 (Japan); Honda, Goichi [Medical Affairs Department, Asahi Kasei Pharma Corporation, 1-105 Kanda Jinbo-cho, Chiyoda-ku, Tokyo 101-8101 (Japan); Suzuki, Koji [Faculty of Pharmaceutical Science, Suzuka University of Medical Science, 3500-3, Minamitamagaki-cho, Suzuka, Mie 513-8679 (Japan); Imai, Hiroshi [Emergency and Critical Care Center, Mie University Hospital, 2-174 Edobashi, Tsu 514-8507 (Japan); Shimaoka, Motomu, E-mail: shimaoka@doc.medic.mie-u.ac.jp [Department of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507 (Japan)

    2016-05-13

    LFA-1 (αLβ2) and Mac-1 (αMβ2) integrins regulate leukocyte trafficking in health and disease by binding primarily to IgSF ligand ICAM-1 and ICAM-2 on endothelial cells. Here we have shown that the anti-coagulant molecule thrombomodulin (TM), found on the surface of endothelial cells, functions as a potentially new ligand for leukocyte integrins. We generated a recombinant extracellular domain of human TM and Fc fusion protein (TM-domains 123-Fc), and showed that pheripheral blood mononuclear cells (PBMCs) bind to TM-domains 123-Fc dependent upon integrin activation. We then demonstrated that αL integrin-blocking mAb, αM integrin-blocking mAb, and β2 integrin-blocking mAb inhibited the binding of PBMCs to TM-domains 123-Fc. Furthermore, we show that the serine/threonine-rich domain (domain 3) of TM is required for the interaction with the LFA-1 (αLβ2) and Mac-1 (αMβ2) integrins to occur on PBMCs. These results demonstrate that the LFA-1 and Mac-1 integrins on leukocytes bind to TM, thereby establishing the molecular and structural basis underlying LFA-1 and Mac-1 integrin interaction with TM on endothelial cells. In fact, integrin-TM interactions might be involved in the dynamic regulation of leukocyte adhesion with endothelial cells. - Highlights: • LFA-1 and Mac-1 integrins bind to the anti-coagulant molecule thrombomodulin. • The serine/threonine-rich domain of thrombomodulin is essential to interact with the LFA-1 and Mac-1 integrins on PBMCs. • Integrin-TM interactions might be involved in the dynamic regulation of leukocyte adhesion with endothelial cells.

  17. Insights into function of PSI domains from structure of the Met receptor PSI domain

    International Nuclear Information System (INIS)

    Kozlov, Guennadi; Perreault, Audrey; Schrag, Joseph D.; Park, Morag; Cygler, Miroslaw; Gehring, Kalle; Ekiel, Irena

    2004-01-01

    PSI domains are cysteine-rich modules found in extracellular fragments of hundreds of signaling proteins, including plexins, semaphorins, integrins, and attractins. Here, we report the solution structure of the PSI domain from the human Met receptor, a receptor tyrosine kinase critical for proliferation, motility, and differentiation. The structure represents a cysteine knot with short regions of secondary structure including a three-stranded antiparallel β-sheet and two α-helices. All eight cysteines are involved in disulfide bonds with the pattern consistent with that for the PSI domain from Sema4D. Comparison with the Sema4D structure identifies a structurally conserved core comprising the N-terminal half of the PSI domain. Interestingly, this part links adjacent SEMA and immunoglobulin domains in the Sema4D structure, suggesting that the PSI domain serves as a wedge between propeller and immunoglobulin domains and is responsible for the correct positioning of the ligand-binding site of the receptor

  18. Resource Unavailability (RU) Per Domain Behavior

    NARCIS (Netherlands)

    Karagiannis, Georgios; Westberg, L.; Bader, A.; Tschofenig, Hannes; Tschofenig, H.

    2006-01-01

    This draft specifies a Per Domain Behavior that provides the ability to Diffserv nodes located outside Diffserv domain(s), e.g., receiver or other Diffserv enabled router to detect when the resources provided by the Diffserv domain(s) are not available. The unavailability of resources in the domain

  19. Small Drinking Water Systems Communication and Outreach Highlights

    Science.gov (United States)

    As part of our small drinking water systems efforts, this poster highlights several communications and outreach highlights that EPA's Office of Research and Development and Office of Water have been undertaking in collaboration with states and the Association of State Drinking Wa...

  20. Recovering protein-protein and domain-domain interactions from aggregation of IP-MS proteomics of coregulator complexes.

    Directory of Open Access Journals (Sweden)

    Amin R Mazloom

    2011-12-01

    Full Text Available Coregulator proteins (CoRegs are part of multi-protein complexes that transiently assemble with transcription factors and chromatin modifiers to regulate gene expression. In this study we analyzed data from 3,290 immuno-precipitations (IP followed by mass spectrometry (MS applied to human cell lines aimed at identifying CoRegs complexes. Using the semi-quantitative spectral counts, we scored binary protein-protein and domain-domain associations with several equations. Unlike previous applications, our methods scored prey-prey protein-protein interactions regardless of the baits used. We also predicted domain-domain interactions underlying predicted protein-protein interactions. The quality of predicted protein-protein and domain-domain interactions was evaluated using known binary interactions from the literature, whereas one protein-protein interaction, between STRN and CTTNBP2NL, was validated experimentally; and one domain-domain interaction, between the HEAT domain of PPP2R1A and the Pkinase domain of STK25, was validated using molecular docking simulations. The scoring schemes presented here recovered known, and predicted many new, complexes, protein-protein, and domain-domain interactions. The networks that resulted from the predictions are provided as a web-based interactive application at http://maayanlab.net/HT-IP-MS-2-PPI-DDI/.

  1. Single-Domain Antibodies As Versatile Affinity Reagents for Analytical and Diagnostic Applications

    Directory of Open Access Journals (Sweden)

    Gualberto Gonzalez-Sapienza

    2017-08-01

    Full Text Available With just three CDRs in their variable domains, the antigen-binding site of camelid heavy-chain-only antibodies (HcAbs has a more limited structural diversity than that of conventional antibodies. Even so, this does not seem to limit their specificity and high affinity as HcAbs against a broad range of structurally diverse antigens have been reported. The recombinant form of their variable domain [nanobody (Nb] has outstanding properties that make Nbs, not just an alternative option to conventional antibodies, but in many cases, these properties allow them to reach analytical or diagnostic performances that cannot be accomplished with conventional antibodies. These attributes include comprehensive representation of the immune specificity in display libraries, easy adaptation to high-throughput screening, exceptional stability, minimal size, and versatility as affinity building block. Here, we critically reviewed each of these properties and highlight their relevance with regard to recent developments in different fields of immunosensing applications.

  2. 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.

  3. Full waveform inversion in the frequency domain using classified time-domain residual wavefields

    Science.gov (United States)

    Son, Woohyun; Koo, Nam-Hyung; Kim, Byoung-Yeop; Lee, Ho-Young; Joo, Yonghwan

    2017-04-01

    We perform the acoustic full waveform inversion in the frequency domain using residual wavefields that have been separated in the time domain. We sort the residual wavefields in the time domain according to the order of absolute amplitudes. Then, the residual wavefields are separated into several groups in the time domain. To analyze the characteristics of the residual wavefields, we compare the residual wavefields of conventional method with those of our residual separation method. From the residual analysis, the amplitude spectrum obtained from the trace before separation appears to have little energy at the lower frequency bands. However, the amplitude spectrum obtained from our strategy is regularized by the separation process, which means that the low-frequency components are emphasized. Therefore, our method helps to emphasize low-frequency components of residual wavefields. Then, we generate the frequency-domain residual wavefields by taking the Fourier transform of the separated time-domain residual wavefields. With these wavefields, we perform the gradient-based full waveform inversion in the frequency domain using back-propagation technique. Through a comparison of gradient directions, we confirm that our separation method can better describe the sub-salt image than the conventional approach. The proposed method is tested on the SEG/EAGE salt-dome model. The inversion results show that our algorithm is better than the conventional gradient based waveform inversion in the frequency domain, especially for deeper parts of the velocity model.

  4. Apoplastic domains and sub-domains in the shoots of etiolated corn seedlings

    Science.gov (United States)

    Epel, B. L.; Bandurski, R. S.

    1990-01-01

    Light Green, an apoplastic probe, was applied to the cut mesocotyl base or to the cut coleoptile apex of etiolated seedlings of Zea mays L. cv. Silver Queen. Probe transport was measured and its tissue distribution determined. In the mesocotyl, there is an apoplastic barrier between cortex and stele. This barrier creates two apoplastic domains which are non-communicating. A kinetic barrier exists between the apoplast of the mesocotyl stele and that of the coleoptile. This kinetic barrier is not absolute and there is limited communication between the apoplasts of the two regions. This kinetic barrier effectively creates two sub-domains. In the coleoptile, there is communication between the apoplast of the vascular strands and that of the surrounding cortical tissue. No apoplastic communication was observed between the coleoptile cortex and the mesocotyl cortex. Thus, the apoplastic space of the coleoptile cortex is a sub-domain of the integrated coleoptile domain and is separate from that of the apoplastic domain of the mesocotyl cortex.

  5. Steady-state configurations of Dzyaloshinskii domain walls driven by field and current

    Energy Technology Data Exchange (ETDEWEB)

    Sánchez-Tejerina, L., E-mail: luis.st@ee.uva.es [Departamento de Electricidad y Electrónica, Facultad de Ciencias, Universidad de Valladolid, 47011 Valladolid (Spain); Departamento de Física Aplicada, Facultad de Ciencias, Universidad de Salamanca, 37011 Salamanca (Spain); Alejos, O. [Departamento de Electricidad y Electrónica, Facultad de Ciencias, Universidad de Valladolid, 47011 Valladolid (Spain); Martínez, E. [Departamento de Física Aplicada, Facultad de Ciencias, Universidad de Salamanca, 37011 Salamanca (Spain)

    2017-02-01

    The dynamics of Dzyaloshinskii domain walls (DDW) in ultrathin ferromagnetic strips with perpendicular magnetic anisotropy, for different values of both perpendicular field and longitudinal current excitation associated to the Spin-Hall effect, has been studied, taking into account different values of the interfacial Dzyaloshinskii-Moriya interaction (DMI). This study has been carried out with the help of the q-Φ one-dimensional model and micromagnetic simulations. We have found that Walker breakdown may be avoided by applying a certain threshold current, even though the inverse effect is also possible. We have also found that, for particular values of field and current, the magnetization within the DDW experiences an abrupt change of orientation, which provokes a change on the contribution of current to the terminal DDW velocity. This effect disappears for sufficiently strong DMI, as it is expected from the model. - Highlights: • Steady-state configurations of Dzyaloshinskii domain walls driven by field and current have been reported. • Field-like torques and Slonczewskii-like torques due to spin-orbit interactions have been considered. • The response is associated with the rotation of the domain wall inner magnetization. • An asymmetric behavior arising from the existence of degenerate states is shown. • The asymmetry results in different travelled distances and/or terminal speeds.

  6. Steady-state configurations of Dzyaloshinskii domain walls driven by field and current

    International Nuclear Information System (INIS)

    Sánchez-Tejerina, L.; Alejos, O.; Martínez, E.

    2017-01-01

    The dynamics of Dzyaloshinskii domain walls (DDW) in ultrathin ferromagnetic strips with perpendicular magnetic anisotropy, for different values of both perpendicular field and longitudinal current excitation associated to the Spin-Hall effect, has been studied, taking into account different values of the interfacial Dzyaloshinskii-Moriya interaction (DMI). This study has been carried out with the help of the q-Φ one-dimensional model and micromagnetic simulations. We have found that Walker breakdown may be avoided by applying a certain threshold current, even though the inverse effect is also possible. We have also found that, for particular values of field and current, the magnetization within the DDW experiences an abrupt change of orientation, which provokes a change on the contribution of current to the terminal DDW velocity. This effect disappears for sufficiently strong DMI, as it is expected from the model. - Highlights: • Steady-state configurations of Dzyaloshinskii domain walls driven by field and current have been reported. • Field-like torques and Slonczewskii-like torques due to spin-orbit interactions have been considered. • The response is associated with the rotation of the domain wall inner magnetization. • An asymmetric behavior arising from the existence of degenerate states is shown. • The asymmetry results in different travelled distances and/or terminal speeds.

  7. Structure-function analysis of the OB and latch domains of chlorella virus DNA ligase.

    Science.gov (United States)

    Samai, Poulami; Shuman, Stewart

    2011-06-24

    Chlorella virus DNA ligase (ChVLig) is a minimized eukaryal ATP-dependent DNA sealing enzyme with an intrinsic nick-sensing function. ChVLig consists of three structural domains, nucleotidyltransferase (NTase), OB-fold, and latch, that envelop the nicked DNA as a C-shaped protein clamp. The OB domain engages the DNA minor groove on the face of the duplex behind the nick, and it makes contacts to amino acids in the NTase domain surrounding the ligase active site. The latch module occupies the DNA major groove flanking the nick. Residues at the tip of the latch contact the NTase domain to close the ligase clamp. Here we performed a structure-guided mutational analysis of the OB and latch domains. Alanine scanning defined seven individual amino acids as essential in vivo (Lys-274, Arg-285, Phe-286, and Val-288 in the OB domain; Asn-214, Phe-215, and Tyr-217 in the latch), after which structure-activity relations were clarified by conservative substitutions. Biochemical tests of the composite nick sealing reaction and of each of the three chemical steps of the ligation pathway highlighted the importance of Arg-285 and Phe-286 in the catalysis of the DNA adenylylation and phosphodiester synthesis reactions. Phe-286 interacts with the nick 5'-phosphate nucleotide and the 3'-OH base pair and distorts the DNA helical conformation at the nick. Arg-285 is a key component of the OB-NTase interface, where it forms a salt bridge to the essential Asp-29 side chain, which is imputed to coordinate divalent metal catalysts during the nick sealing steps.

  8. Structure-Function Analysis of the OB and Latch Domains of Chlorella Virus DNA Ligase*

    Science.gov (United States)

    Samai, Poulami; Shuman, Stewart

    2011-01-01

    Chlorella virus DNA ligase (ChVLig) is a minimized eukaryal ATP-dependent DNA sealing enzyme with an intrinsic nick-sensing function. ChVLig consists of three structural domains, nucleotidyltransferase (NTase), OB-fold, and latch, that envelop the nicked DNA as a C-shaped protein clamp. The OB domain engages the DNA minor groove on the face of the duplex behind the nick, and it makes contacts to amino acids in the NTase domain surrounding the ligase active site. The latch module occupies the DNA major groove flanking the nick. Residues at the tip of the latch contact the NTase domain to close the ligase clamp. Here we performed a structure-guided mutational analysis of the OB and latch domains. Alanine scanning defined seven individual amino acids as essential in vivo (Lys-274, Arg-285, Phe-286, and Val-288 in the OB domain; Asn-214, Phe-215, and Tyr-217 in the latch), after which structure-activity relations were clarified by conservative substitutions. Biochemical tests of the composite nick sealing reaction and of each of the three chemical steps of the ligation pathway highlighted the importance of Arg-285 and Phe-286 in the catalysis of the DNA adenylylation and phosphodiester synthesis reactions. Phe-286 interacts with the nick 5′-phosphate nucleotide and the 3′-OH base pair and distorts the DNA helical conformation at the nick. Arg-285 is a key component of the OB-NTase interface, where it forms a salt bridge to the essential Asp-29 side chain, which is imputed to coordinate divalent metal catalysts during the nick sealing steps. PMID:21527793

  9. DIMA 3.0: Domain Interaction Map.

    Science.gov (United States)

    Luo, Qibin; Pagel, Philipp; Vilne, Baiba; Frishman, Dmitrij

    2011-01-01

    Domain Interaction MAp (DIMA, available at http://webclu.bio.wzw.tum.de/dima) is a database of predicted and known interactions between protein domains. It integrates 5807 structurally known interactions imported from the iPfam and 3did databases and 46,900 domain interactions predicted by four computational methods: domain phylogenetic profiling, domain pair exclusion algorithm correlated mutations and domain interaction prediction in a discriminative way. Additionally predictions are filtered to exclude those domain pairs that are reported as non-interacting by the Negatome database. The DIMA Web site allows to calculate domain interaction networks either for a domain of interest or for entire organisms, and to explore them interactively using the Flash-based Cytoscape Web software.

  10. Clinical highlights from Amsterdam

    Directory of Open Access Journals (Sweden)

    Jouke T. Annema

    2016-07-01

    Full Text Available This article contains highlights and a selection of the scientific advances from the Clinical Assembly that were presented at the 2015 European Respiratory Society International Congress in Amsterdam, the Netherlands. The most relevant topics for clinicians will be discussed, covering a wide range of areas including interventional pulmonology, rehabilitation and chronic care, thoracic imaging, diffuse and parenchymal lung diseases, and general practice and primary care. In this comprehensive review, exciting novel data will be discussed and put into perspective.

  11. Apo and ligand-bound structures of ModA from the archaeon Methanosarcina acetivorans.

    Science.gov (United States)

    Chan, Sum; Giuroiu, Iulia; Chernishof, Irina; Sawaya, Michael R; Chiang, Janet; Gunsalus, Robert P; Arbing, Mark A; Perry, L Jeanne

    2010-03-01

    The trace-element oxyanion molybdate, which is required for the growth of many bacterial and archaeal species, is transported into the cell by an ATP-binding cassette (ABC) transporter superfamily uptake system called ModABC. ModABC consists of the ModA periplasmic solute-binding protein, the integral membrane-transport protein ModB and the ATP-binding and hydrolysis cassette protein ModC. In this study, X-ray crystal structures of ModA from the archaeon Methanosarcina acetivorans (MaModA) have been determined in the apoprotein conformation at 1.95 and 1.69 A resolution and in the molybdate-bound conformation at 2.25 and 2.45 A resolution. The overall domain structure of MaModA is similar to other ModA proteins in that it has a bilobal structure in which two mixed alpha/beta domains are linked by a hinge region. The apo MaModA is the first unliganded archaeal ModA structure to be determined: it exhibits a deep cleft between the two domains and confirms that upon binding ligand one domain is rotated towards the other by a hinge-bending motion, which is consistent with the 'Venus flytrap' model seen for bacterial-type periplasmic binding proteins. In contrast to the bacterial ModA structures, which have tetrahedral coordination of their metal substrates, molybdate-bound MaModA employs octahedral coordination of its substrate like other archaeal ModA proteins.

  12. Highlights from CMS

    CERN Document Server

    Autermann, Christian

    2018-01-01

    This article summarizes the latest highlights from the CMS experiment as presented at the Lepton Photon conference 2017 in Guangzhou, China. A selection of the latest physics results, the latest detector upgrades, and the current detector status are discussed. CMS has analyzed the full dataset of proton-proton collision data delivered by the LHC in 2016 at a center-of-mass energy of $13$\\,TeV corresponding to an integrated luminosity of $40$\\,fb$^{-1}$. The leap in center-of-mass energy and in luminosity with respect to the $7$ and $8$\\,TeV runs enabled interesting and relevant new physics results. A new silicon pixel tracking detector was installed during the LHC shutdown 2016/17 and has successfully started operation.

  13. Electric transport in the Netherlands. Highlights 2012; Elektrisch vervoer in Nederland. Highlights 2012

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2013-03-15

    Businesses, social and educational institutions and governmental institutes work together to accelerate electric transport and to discover and exploit economic opportunities. In 2012, many activities were carried out and results achieved, of which the highlights are presented in this brochure [Dutch] Bedrijfsleven, maatschappelijke- en kennisinstellingen en overheden werken samen aan versnelling van elektrisch vervoer en het ontdekken en benutten van economische kansen. In 2012 werden veel activiteiten uitgevoerd en resultaten geboekt, waarvan in deze brochure verslag wordt gedaan.

  14. Domain fusion analysis by applying relational algebra to protein sequence and domain databases.

    Science.gov (United States)

    Truong, Kevin; Ikura, Mitsuhiko

    2003-05-06

    Domain fusion analysis is a useful method to predict functionally linked proteins that may be involved in direct protein-protein interactions or in the same metabolic or signaling pathway. As separate domain databases like BLOCKS, PROSITE, Pfam, SMART, PRINTS-S, ProDom, TIGRFAMs, and amalgamated domain databases like InterPro continue to grow in size and quality, a computational method to perform domain fusion analysis that leverages on these efforts will become increasingly powerful. This paper proposes a computational method employing relational algebra to find domain fusions in protein sequence databases. The feasibility of this method was illustrated on the SWISS-PROT+TrEMBL sequence database using domain predictions from the Pfam HMM (hidden Markov model) database. We identified 235 and 189 putative functionally linked protein partners in H. sapiens and S. cerevisiae, respectively. From scientific literature, we were able to confirm many of these functional linkages, while the remainder offer testable experimental hypothesis. Results can be viewed at http://calcium.uhnres.utoronto.ca/pi. As the analysis can be computed quickly on any relational database that supports standard SQL (structured query language), it can be dynamically updated along with the sequence and domain databases, thereby improving the quality of predictions over time.

  15. Insights into the Inhibition of the p90 Ribosomal S6 Kinase (RSK) by the Flavonol Glycoside SL0101 from the 1.5 Å Crystal Structure of the N-Terminal Domain of RSK2 with Bound Inhibitor

    Energy Technology Data Exchange (ETDEWEB)

    Utepbergenov, Darkhan; Derewenda, Urszula; Olekhnovich, Natalya; Szukalska, Gabriela; Banerjee, Budhaditya; Hilinski, Michael K.; Lannigan, Deborah A.; Stukenberg, P. Todd; Derewenda, Zygmunt S. (Lodz - Poland); (UV)

    2012-09-11

    The p90 ribosomal S6 family of kinases (RSK) are potential drug targets, due to their involvement in cancer and other pathologies. There are currently only two known selective inhibitors of RSK, but the basis for selectivity is not known. One of these inhibitors is a naturally occurring kaempferol-a-l-diacetylrhamnoside, SL0101. Here, we report the crystal structure of the complex of the N-terminal kinase domain of the RSK2 isoform with SL0101 at 1.5 {angstrom} resolution. The refined atomic model reveals unprecedented structural reorganization of the protein moiety, as compared to the nucleotide-bound form. The entire N-lobe, the hinge region, and the aD-helix undergo dramatic conformational changes resulting in a rearrangement of the nucleotide binding site with concomitant formation of a highly hydrophobic pocket spatially suited to accommodate SL0101. These unexpected results will be invaluable in further optimization of the SL0101 scaffold as a promising lead for a novel class of kinase inhibitors.

  16. Single-domain versus two-domain configuration in thin ferromagnetic prisms

    International Nuclear Information System (INIS)

    Pini, Maria Gloria; Politi, Paolo

    2007-01-01

    Thin ferromagnetic elements in the form of rectangular prisms are theoretically investigated in order to study the transition from single-domain to two-domain state, with changing the in-plane aspect ratio p. We address two main questions: first, how general is the transition; second, how the critical value p c depends on the physical parameters. We use two complementary methods: discrete-lattice calculations and a micromagnetic continuum approach. Ultrathin films do not appear to split in two domains. Instead, thicker films may undergo the above transition. We have used the continuum approach to analyze recent magnetic force microscopy observations in 30nm-thick patterned permalloy elements, finding a good agreement for p c

  17. 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.

  18. Prediction Reweighting for Domain Adaptation.

    Science.gov (United States)

    Shuang Li; Shiji Song; Gao Huang

    2017-07-01

    There are plenty of classification methods that perform well when training and testing data are drawn from the same distribution. However, in real applications, this condition may be violated, which causes degradation of classification accuracy. Domain adaptation is an effective approach to address this problem. In this paper, we propose a general domain adaptation framework from the perspective of prediction reweighting, from which a novel approach is derived. Different from the major domain adaptation methods, our idea is to reweight predictions of the training classifier on testing data according to their signed distance to the domain separator, which is a classifier that distinguishes training data (from source domain) and testing data (from target domain). We then propagate the labels of target instances with larger weights to ones with smaller weights by introducing a manifold regularization method. It can be proved that our reweighting scheme effectively brings the source and target domains closer to each other in an appropriate sense, such that classification in target domain becomes easier. The proposed method can be implemented efficiently by a simple two-stage algorithm, and the target classifier has a closed-form solution. The effectiveness of our approach is verified by the experiments on artificial datasets and two standard benchmarks, a visual object recognition task and a cross-domain sentiment analysis of text. Experimental results demonstrate that our method is competitive with the state-of-the-art domain adaptation algorithms.

  19. Investigation of phosphotyrosine recognition by the SH2 domain of the Src kinase.

    Science.gov (United States)

    Bradshaw, J M; Mitaxov, V; Waksman, G

    1999-11-05

    this investigation highlight the importance of a single critical interaction, the buried ionic bond between the phosphate of the pTyr and Arg betaB5 of the SH2 domain, driving the binding of SH2 domains to tyrosine phosphorylated targets. Copyright 1999 Academic Press.

  20. Interplay of domain walls and magnetization rotation on dynamic magnetization process in iron/polymer–matrix soft magnetic composites

    Energy Technology Data Exchange (ETDEWEB)

    Dobák, Samuel, E-mail: samuel.dobak@student.upjs.sk [Institute of Physics, Faculty of Science, Pavol Jozef Šafárik University, Park Angelinum 9, 041 54 Košice (Slovakia); Füzer, Ján; Kollár, Peter [Institute of Physics, Faculty of Science, Pavol Jozef Šafárik University, Park Angelinum 9, 041 54 Košice (Slovakia); Fáberová, Mária; Bureš, Radovan [Institute of Materials Research, Slovak Academy of Sciences, Watsonova 47, 043 53 Košice (Slovakia)

    2017-03-15

    This study sheds light on the dynamic magnetization process in iron/resin soft magnetic composites from the viewpoint of quantitative decomposition of their complex permeability spectra into the viscous domain wall motion and magnetization rotation. We present a comprehensive view on this phenomenon over the broad family of samples with different average particles dimension and dielectric matrix content. The results reveal the pure relaxation nature of magnetization processes without observation of spin resonance. The smaller particles and higher amount of insulating resin result in the prevalence of rotations over domain wall movement. The findings are elucidated in terms of demagnetizing effects rising from the heterogeneity of composite materials. - Highlights: • A first decomposition of complex permeability into domain wall and rotation parts in soft magnetic composites. • A pure relaxation nature of dynamic magnetization processes. • A complete loss separation in soft magnetic composites. • The domain walls activity is considerably suppressed in composites with smaller iron particles and higher matrix content. • The demagnetizing field acts as a significant factor at the dynamic magnetization process.

  1. A localized interaction surface for voltage-sensing domains on the pore domain of a K+ channel.

    Science.gov (United States)

    Li-Smerin, Y; Hackos, D H; Swartz, K J

    2000-02-01

    Voltage-gated K+ channels contain a central pore domain and four surrounding voltage-sensing domains. How and where changes in the structure of the voltage-sensing domains couple to the pore domain so as to gate ion conduction is not understood. The crystal structure of KcsA, a bacterial K+ channel homologous to the pore domain of voltage-gated K+ channels, provides a starting point for addressing this question. Guided by this structure, we used tryptophan-scanning mutagenesis on the transmembrane shell of the pore domain in the Shaker voltage-gated K+ channel to localize potential protein-protein and protein-lipid interfaces. Some mutants cause only minor changes in gating and when mapped onto the KcsA structure cluster away from the interface between pore domain subunits. In contrast, mutants producing large changes in gating tend to cluster near this interface. These results imply that voltage-sensing domains interact with localized regions near the interface between adjacent pore domain subunits.

  2. 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

  3. Regional climate projections for the MENA-CORDEX domain: analysis of projected temperature and precipitation changes

    Science.gov (United States)

    Hänsler, Andreas; Weber, Torsten; Eggert, Bastian; Saeed, Fahad; Jacob, Daniela

    2014-05-01

    Within the CORDEX initiative a multi-model suite of regionalized climate change information will be made available for several regions of the world. The German Climate Service Center (CSC) is taking part in this initiative by applying the regional climate model REMO to downscale global climate projections of different coupled general circulation models (GCMs) for several CORDEX domains. Also for the MENA-CORDEX domain, a set of regional climate change projections has been established at the CSC by downscaling CMIP5 projections of the Max-Planck-Institute Earth System Model (MPI-ESM) for the scenarios RCP4.5 and RCP8.5 with the regional model REMO for the time period from 1950 to 2100 to a horizontal resolution of 0.44 degree. In this study we investigate projected changes in future climate conditions over the domain towards the end of the 21st century. Focus in the analysis is given to projected changes in the temperature and rainfall characteristics and their differences for the two scenarios will be highlighted.

  4. AGARD Highlights 90/2. Part 2

    Science.gov (United States)

    1990-09-01

    avec Technology programme, in close l’industrie, le monde de la recherche, de collaboration with industry, education , l’dducation et avec la Ddldgation...supplied by remote adrospatiale. sensing. Programme de localisation: Localisation programme: * CLS CLS La socidtd CLS commercialise des The company...development of connaissances - 116ducation knowledge - Education Dans le domaine de la recherche, In the field of research, close links des liens

  5. Structural Insights into the HWE Histidine Kinase Family: The Brucella Blue Light-Activated Histidine Kinase Domain.

    Science.gov (United States)

    Rinaldi, Jimena; Arrar, Mehrnoosh; Sycz, Gabriela; Cerutti, María Laura; Berguer, Paula M; Paris, Gastón; Estrín, Darío Ariel; Martí, Marcelo Adrián; Klinke, Sebastián; Goldbaum, Fernando Alberto

    2016-03-27

    In response to light, as part of a two-component system, the Brucella blue light-activated histidine kinase (LOV-HK) increases its autophosphorylation, modulating the virulence of this microorganism. The Brucella histidine kinase (HK) domain belongs to the HWE family, for which there is no structural information. The HWE family is exclusively present in proteobacteria and usually coupled to a wide diversity of light sensor domains. This work reports the crystal structure of the Brucella HK domain, which presents two different dimeric assemblies in the asymmetric unit: one similar to the already described canonical parallel homodimers (C) and the other, an antiparallel non-canonical (NC) dimer, each with distinct relative subdomain orientations and dimerization interfaces. Contrary to these crystallographic structures and unlike other HKs, in solution, the Brucella HK domain is monomeric and still active, showing an astonishing instability of the dimeric interface. Despite this instability, using cross-linking experiments, we show that the C dimer is the functionally relevant species. Mutational analysis demonstrates that the autophosphorylation activity occurs in cis. The different relative subdomain orientations observed for the NC and C states highlight the large conformational flexibility of the HK domain. Through the analysis of these alternative conformations by means of molecular dynamics simulations, we also propose a catalytic mechanism for Brucella LOV-HK. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Signatures of pleiotropy, economy and convergent evolution in a domain-resolved map of human-virus protein-protein interaction networks.

    Directory of Open Access Journals (Sweden)

    Sara Garamszegi

    Full Text Available A central challenge in host-pathogen systems biology is the elucidation of general, systems-level principles that distinguish host-pathogen interactions from within-host interactions. Current analyses of host-pathogen and within-host protein-protein interaction networks are largely limited by their resolution, treating proteins as nodes and interactions as edges. Here, we construct a domain-resolved map of human-virus and within-human protein-protein interaction networks by annotating protein interactions with high-coverage, high-accuracy, domain-centric interaction mechanisms: (1 domain-domain interactions, in which a domain in one protein binds to a domain in a second protein, and (2 domain-motif interactions, in which a domain in one protein binds to a short, linear peptide motif in a second protein. Analysis of these domain-resolved networks reveals, for the first time, significant mechanistic differences between virus-human and within-human interactions at the resolution of single domains. While human proteins tend to compete with each other for domain binding sites by means of sequence similarity, viral proteins tend to compete with human proteins for domain binding sites in the absence of sequence similarity. Independent of their previously established preference for targeting human protein hubs, viral proteins also preferentially target human proteins containing linear motif-binding domains. Compared to human proteins, viral proteins participate in more domain-motif interactions, target more unique linear motif-binding domains per residue, and contain more unique linear motifs per residue. Together, these results suggest that viruses surmount genome size constraints by convergently evolving multiple short linear motifs in order to effectively mimic, hijack, and manipulate complex host processes for their survival. Our domain-resolved analyses reveal unique signatures of pleiotropy, economy, and convergent evolution in viral

  7. Hydrology Domain Cyberinfrastructures: Successes, Challenges, and Opportunities

    Science.gov (United States)

    Horsburgh, J. S.

    2015-12-01

    Anticipated changes to climate, human population, land use, and urban form will alter the hydrology and availability of water within the water systems on which the world's population relies. Understanding the effects of these changes will be paramount in sustainably managing water resources, as well as maintaining associated capacity to provide ecosystem services (e.g., regulating flooding, maintaining instream flow during dry periods, cycling nutrients, and maintaining water quality). It will require better information characterizing both natural and human mediated hydrologic systems and enhanced ability to generate, manage, store, analyze, and share growing volumes of observational data. Over the past several years, a number of hydrology domain cyberinfrastructures have emerged or are currently under development that are focused on providing integrated access to and analysis of data for cross-domain synthesis studies. These include the Consortium of Universities for the Advancement of Hydrologic Science, Inc. (CUAHSI) Hydrologic Information System (HIS), the Critical Zone Observatory Information System (CZOData), HyroShare, the BiG CZ software system, and others. These systems have focused on sharing, integrating, and analyzing hydrologic observations data. This presentation will describe commonalities and differences in the cyberinfrastructure approaches used by these projects and will highlight successes and lessons learned in addressing the challenges of big and complex data. It will also identify new challenges and opportunities for next generation cyberinfrastructure and a next generation of cyber-savvy scientists and engineers as developers and users.

  8. Automatic Online Lecture Highlighting Based on Multimedia Analysis

    Science.gov (United States)

    Che, Xiaoyin; Yang, Haojin; Meinel, Christoph

    2018-01-01

    Textbook highlighting is widely considered to be beneficial for students. In this paper, we propose a comprehensive solution to highlight the online lecture videos in both sentence- and segment-level, just as is done with paper books. The solution is based on automatic analysis of multimedia lecture materials, such as speeches, transcripts, and…

  9. Research resource: novel structural insights bridge gaps in glycoprotein hormone receptor analyses.

    Science.gov (United States)

    Kreuchwig, Annika; Kleinau, Gunnar; Krause, Gerd

    2013-08-01

    The first version of a glycoprotein hormone receptor (GPHR) information resource was designed to link functional with structural GPHR information, in order to support sequence-structure-function analysis of the LH, FSH, and TSH receptors (http://ssfa-gphr.de). However, structural information on a binding- and signaling-sensitive extracellular fragment (∼100 residues), the hinge region, had been lacking. A new FSHR crystal structure of the hormone-bound extracellular domain has recently been solved. The structure comprises the leucine-rich repeat domain and most parts of the hinge region. We have not only integrated the new FSHR/FSH structure and the derived homology models of TSHR/TSH, LHCGR/CG, and LHCGR/LH into our web-based information resource, but have additionally provided novel tools to analyze the advanced structural features, with the common characteristics and distinctions between GPHRs, in a more precise manner. The hinge region with its second hormone-binding site allows us to assign functional data to the new structural features between hormone and receptor, such as binding details of a sulfated tyrosine (conserved throughout the GPHRs) extending into a pocket of the hormone. We have also implemented a protein interface analysis tool that enables the identification and visualization of extracellular contact points between interaction partners. This provides a starting point for comparing the binding patterns of GPHRs. Together with the mutagenesis data stored in the database, this will help to decipher the essential residues for ligand recognition and the molecular mechanisms of signal transduction, extending from the extracellular hormone-binding site toward the intracellular G protein-binding sites.

  10. Measurement of the nucleation and domain depinning field in a single Co/Pt multilayer dot by Anomalous Hall effect

    International Nuclear Information System (INIS)

    Delalande, M.; Vries, J. de; Abelmann, L.; Lodder, J.C.

    2012-01-01

    Co/Pt multilayer dots with perpendicular anisotropy and with diameters of 250 and 350 nm were fabricated on top of a Hall cross configuration. The angular dependence of the magnetic reversal of the individual dot was investigated by Anomalous Hall effect measurements. At near in-plane angles (85° with the magnetic easy axis) the dot switches partially into a stable two-domain state. This allows for separate analysis of the angular dependence of both the field required for nucleation of a reversed domain, and the field required for depinning of the domain wall. The angular dependence of the depinning field fits accurately to a 1/cos(θ) behavior, whereas the angular dependence of the nucleation field shows a minimum close to 45°. The latter dependency can be accurately fitted to the modified Kondorsky model proposed by Schumacher . - Highlights: ► Reversal takes place by nucleation and subsequent propagation of a domain wall. ► The domain wall can be trapped in the dot at near in-plane field angles. ► Angular dependence of depinning is accurately predicted by the Kondorsky model. ► Angular dependence of nucleation can be fitted to a modified Kondorksy model.

  11. Interoperable domain models: the ISO land administration domain model LADM and its external classes

    CSIR Research Space (South Africa)

    Lemmen, CHJ

    2011-09-01

    Full Text Available This paper provides a brief overview of one of the first spatial domain standards: a standard for the domain of Land Administration (LA). This standard is in the draft stage of development now (May 2011). The development of domain standards is a...

  12. Palliativedrugs.com therapeutic highlights: gabapentin

    Directory of Open Access Journals (Sweden)

    Twycross Robert

    2003-01-01

    Full Text Available This is the second in a series of highlights drawn from the www.palliativedrugs.com website. The website provides free access to the Palliative Care Formulary, a monthly newsletter and a bulletin board for advice to be given and received. With almost 10,000 professional members it is the largest palliative care resource of its kind.

  13. 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.

  14. 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)

  15. Dissect Kif5b in nuclear positioning during myogenesis: The light chain binding domain and the autoinhibitory peptide are both indispensable

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Zai, E-mail: wangzai81@hotmail.com [Department of Biochemistry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam (Hong Kong); Institute of Clinical Medical Sciences, China–Japan Friendship Hospital, Beijing (China); Xue, Wenqian; Li, Xiuling; Lin, Raozhou [Department of Biochemistry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam (Hong Kong); Cui, Ju [Department of Biochemistry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam (Hong Kong); Beijing Institute of Geriatrics, Beijing Hospital, Ministry of Health (China); Huang, Jian-Dong, E-mail: jdhuang@hku.hk [Department of Biochemistry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam (Hong Kong)

    2013-03-08

    Highlights: ► Kif5b localizes at myonuclear membrane and is responsible for nuclear dispersion. ► Kif5b stalk/tail domain contains signal for nuclear membrane targeting. ► Kif5b stalk/tail domain directly binds to a nesprin 4 in vitro. ► KLC binding domain and autoinhibitory peptide are both functionally indispensable. -- Abstract: The microtubule motor kinesin-1 is responsible for the nuclear positioning during myogenesis. Here we show that the coiled-coil stalk/tail domain containing the kinesin light chain (KLC) binding sites targets to the perinuclear region like endogenous Kif5b, while the globular tail domain cannot. To investigate which fragments of kinesin heavy chain (Kif5b) is responsible for the myonuclear positioning, we transfect Kif5b expression constructs into Kif5b deficient myoblasts and test their ability to rescue the myonuclear phenotype. We find that the KLC binding domain and the autoinhibitory peptide in the globular tail region are both indispensable for the nuclear membrane localization of Kif5b and the kinesin-1-mediated myonuclear positioning. These results suggest that while the KLC binding domain may directly targets Kif5b to the myonuclear membrane, the autoinhibitory peptide may play an indirect role in regulating the kinesin-1-mediated myonuclear positioning.

  16. Domain Modeling for Adaptive Training and Education in Support of the US Army Learning Model-Research Outline

    Science.gov (United States)

    2015-06-01

    Definitions are provided for this section to distinguish between adaptive training and education elements and also to highlight their relationships ...illustrate this point Franke (2011) asserts that through the use of case study examples, instruction can provide the pedagogical foundation for decision...a prime example of an adaptive training and education system: a learner or trainee model, an instructional or pedagogical model, a domain model

  17. Functional interchangeability of late domains, late domain cofactors and ubiquitin in viral budding.

    Directory of Open Access Journals (Sweden)

    Maria Zhadina

    2010-10-01

    Full Text Available The membrane scission event that separates nascent enveloped virions from host cell membranes often requires the ESCRT pathway, which can be engaged through the action of peptide motifs, termed late (L- domains, in viral proteins. Viral PTAP and YPDL-like L-domains bind directly to the ESCRT-I and ALIX components of the ESCRT pathway, while PPxY motifs bind Nedd4-like, HECT-domain containing, ubiquitin ligases (e.g. WWP1. It has been unclear precisely how ubiquitin ligase recruitment ultimately leads to particle release. Here, using a lysine-free viral Gag protein derived from the prototypic foamy virus (PFV, where attachment of ubiquitin to Gag can be controlled, we show that several different HECT domains can replace the WWP1 HECT domain in chimeric ubiquitin ligases and drive budding. Moreover, artificial recruitment of isolated HECT domains to Gag is sufficient to stimulate budding. Conversely, the HECT domain becomes dispensable if the other domains of WWP1 are directly fused to an ESCRT-1 protein. In each case where budding is driven by a HECT domain, its catalytic activity is essential, but Gag ubiquitination is dispensable, suggesting that ubiquitin ligation to trans-acting proteins drives budding. Paradoxically, however, we also demonstrate that direct fusion of a ubiquitin moiety to the C-terminus of PFV Gag can also promote budding, suggesting that ubiquitination of Gag can substitute for ubiquitination of trans-acting proteins. Depletion of Tsg101 and ALIX inhibits budding that is dependent on ubiquitin that is fused to Gag, or ligated to trans-acting proteins through the action of a PPxY motif. These studies underscore the flexibility in the ways that the ESCRT pathway can be engaged, and suggest a model in which the identity of the protein to which ubiquitin is attached is not critical for subsequent recruitment of ubiquitin-binding components of the ESCRT pathway and viral budding to proceed.

  18. Hotspots of missense mutation identify novel neurodevelopmental disorder genes and functional domains

    Science.gov (United States)

    Geisheker, Madeleine R.; Heymann, Gabriel; Wang, Tianyun; Coe, Bradley P.; Turner, Tychele N.; Stessman, Holly A.F.; Hoekzema, Kendra; Kvarnung, Malin; Shaw, Marie; Friend, Kathryn; Liebelt, Jan; Barnett, Christopher; Thompson, Elizabeth M.; Haan, Eric; Guo, Hui; Anderlid, Britt-Marie; Nordgren, Ann; Lindstrand, Anna; Vandeweyer, Geert; Alberti, Antonino; Avola, Emanuela; Vinci, Mirella; Giusto, Stefania; Pramparo, Tiziano; Pierce, Karen; Nalabolu, Srinivasa; Michaelson, Jacob J.; Sedlacek, Zdenek; Santen, Gijs W.E.; Peeters, Hilde; Hakonarson, Hakon; Courchesne, Eric; Romano, Corrado; Kooy, R. Frank; Bernier, Raphael A.; Nordenskjöld, Magnus; Gecz, Jozef; Xia, Kun; Zweifel, Larry S.; Eichler, Evan E.

    2017-01-01

    Although de novo missense mutations have been predicted to account for more cases of autism than gene-truncating mutations, most research has focused on the latter. We identified the properties of de novo missense mutations in patients with neurodevelopmental disorders (NDDs) and highlight 35 genes with excess missense mutations. Additionally, 40 amino acid sites were recurrently mutated in 36 genes, and targeted sequencing of 20 sites in 17,689 NDD patients identified 21 new patients with identical missense mutations. One recurrent site (p.Ala636Thr) occurs in a glutamate receptor subunit, GRIA1. This same amino acid substitution in the homologous but distinct mouse glutamate receptor subunit Grid2 is associated with Lurcher ataxia. Phenotypic follow-up in five individuals with GRIA1 mutations shows evidence of specific learning disabilities and autism. Overall, we find significant clustering of de novo mutations in 200 genes, highlighting specific functional domains and synaptic candidate genes important in NDD pathology. PMID:28628100

  19. Highlights in emergency medicine medical education research: 2008.

    Science.gov (United States)

    Farrell, Susan E; Coates, Wendy C; Khun, Gloria J; Fisher, Jonathan; Shayne, Philip; Lin, Michelle

    2009-12-01

    The purpose of this article is to highlight medical education research studies published in 2008 that were methodologically superior and whose outcomes were pertinent to teaching and education in emergency medicine. Through a PubMed search of the English language literature in 2008, 30 medical education research studies were independently identified as hypothesis-testing investigations and measurements of educational interventions. Six reviewers independently rated and scored all articles based on eight anchors, four of which related to methodologic criteria. Articles were ranked according to their total rating score. A ranking agreement among the reviewers of 83% was established a priori as a minimum for highlighting articles in this review. Five medical education research studies met the a priori criteria for inclusion and are reviewed and summarized here. Four of these employed experimental or quasi-experimental methodology. Although technology was not a component of the structured literature search employed to identify the candidate articles for this review, 14 of the articles identified, including four of the five highlighted articles, employed or studied technology as a focus of the educational research. Overall, 36% of the reviewed studies were supported by funding; three of the highlighted articles were funded studies. This review highlights quality medical education research studies published in 2008, with outcomes of relevance to teaching and education in emergency medicine. It focuses on research methodology, notes current trends in the use of technology for learning in emergency medicine, and suggests future avenues for continued rigorous study in education.

  20. Effect of the growth conditions on the anisotropy, domain structures and the relaxation in Co thin films

    Energy Technology Data Exchange (ETDEWEB)

    Mallik, Srijani; Mallick, Sougata; Bedanta, Subhankar, E-mail: sbedanta@niser.ac.in

    2017-04-15

    We report a systematic study on the anisotropy symmetry, magnetic domains and magnetic relaxation behavior in Co thin films deposited on MgO (001) substrate by varying (i) the pre-annealing condition and (ii) the speed of substrate rotation during deposition. Substrate annealing prior to deposition leads to the formation of textured thin films. On contrary Co films prepared without substrate pre-annealing exhibit polycrystalline nature. Surface topography imaged by atomic force microscopy (AFM) depicts a profound effect of growth condition on grain size and its distribution. Magnetic hysteresis measurement along with simultaneous domain imaging has been performed by magneto optic Kerr effect (MOKE) based microscope by varying the angle (ϕ) between the easy axis and the direction of applied magnetic field. We observed the existence of cubic and uniaxial anisotropy due to the presence of substrate annealing and oblique angular deposition, respectively. Along the easy axis, magnetization reversal is governed by 180° domain wall motion via branched domains. However, for easy axis<ϕdomains appear in addition to branched domains during the reversal process. We observed that the magnetic relaxation behavior under constant magnetic field strongly depends on the size and distribution of the grains. - Highlights: • This article provides a systematic study of textured growth of Co on MgO(001) substrate. • The structure has clear implication on the magnetic properties. • The magnetic relaxation has been studied for both textured and polycrystalline films.

  1. A smart segmented blade system for reducing weight of the wind turbine rotor

    International Nuclear Information System (INIS)

    Lu, Hongya; Zeng, Pan; Lei, Liping; Yang, Yabin; Xu, Yuejie; Qian, Lingyun

    2014-01-01

    Highlights: • A segmented blade system to light the wind turbine rotor is proposed. • The experiments in the wind tunnel and the numerical calculation are combined to validate the effectiveness of the design. • The moment of the blade below the hinged location are alleviated. • The mounting locations of the hinged rods significantly affect the moment distribution on the blade. • The gross weight of the blade can be reduced by 35.4%. - Abstract: The paper proposes a novel design concept for the wind turbine rotors. The design is composed of the segmented blades and a hinged-rods support structure (SBHR) as a means of reducing weight through alleviating the moment on the blade. A prototype of the design is manufactured. Focusing on the hinged-rods support structure (HRSS), a method combining the experiments and numerical calculation is developed to analyze its feasibility. The experiments in the wind tunnel platform were conducted to measure the loads at the root of the isolated blade and in the rods. A numerical model was developed to describe the designed wind turbine rotor using the measured loads in experiments. In the model, the mounting locations of the hinged rods significantly affected the moment distribution on the blade. Thus, two dimensionless indexes were determined to analyze its influences. The model perfectly explain the characteristics of the novel structure under different configurations. The results demonstrated that the moment of the blade below the hinged location were alleviated, which reduced the requirements for the material. A 43.1% reduction of the maximum moment can be achieved in the design. In addition, the gross reduced weight of the blade was estimated to be 35.4% based on the blade mass distribution along the span

  2. Tourette syndrome research highlights 2015

    Science.gov (United States)

    Richards, Cheryl A.; Black, Kevin J.

    2016-01-01

    We present selected highlights from research that appeared during 2015 on Tourette syndrome and other tic disorders. Topics include phenomenology, comorbidities, developmental course, genetics, animal models, neuroimaging, electrophysiology, pharmacology, and treatment. We briefly summarize articles whose results we believe may lead to new treatments, additional research or modifications in current models of TS. PMID:27429744

  3. KEJAHATAN NAMA DOMAIN BERKAITAN DENGAN MEREK

    Directory of Open Access Journals (Sweden)

    Muhammad Nizar

    2018-02-01

    Full Text Available Indonesia already has an ITE Law governing domain names in general terms and on certain provisions in chapter VI, but the regulation of domain name crimes is not regulated in the ITE Law as mandated in the academic draft of the ITE Bill. The absence of regulation of domain name norm in the ITE Law creates problems with registrant of domain name (registrant which deliberately register the domain name is bad faith. The characteristic of a crime in a domain name relating to the mark is that the registered domain name has an equation in essence with another party’s well-known brand, the act of doing so by exploiting a reputation for well-known or previously commercially valuable names as domain names for addresses for sites (websites it manages. The Prosecutor may include articles of the KUHP in filing his indictment before the Court during the absence of special regulatory provisions concerning domain name crime.

  4. Ligand binding by PDZ domains

    DEFF Research Database (Denmark)

    Chi, Celestine N.; Bach, Anders; Strømgaard, Kristian

    2012-01-01

    , for example, are particularly rich in these domains. The general function of PDZ domains is to bring proteins together within the appropriate cellular compartment, thereby facilitating scaffolding, signaling, and trafficking events. The many functions of PDZ domains under normal physiological as well...... as pathological conditions have been reviewed recently. In this review, we focus on the molecular details of how PDZ domains bind their protein ligands and their potential as drug targets in this context....

  5. Polar Domain Discovery with Sparkler

    Science.gov (United States)

    Duerr, R.; Khalsa, S. J. S.; Mattmann, C. A.; Ottilingam, N. K.; Singh, K.; Lopez, L. A.

    2017-12-01

    The scientific web is vast and ever growing. It encompasses millions of textual, scientific and multimedia documents describing research in a multitude of scientific streams. Most of these documents are hidden behind forms which require user action to retrieve and thus can't be directly accessed by content crawlers. These documents are hosted on web servers across the world, most often on outdated hardware and network infrastructure. Hence it is difficult and time-consuming to aggregate documents from the scientific web, especially those relevant to a specific domain. Thus generating meaningful domain-specific insights is currently difficult. We present an automated discovery system (Figure 1) using Sparkler, an open-source, extensible, horizontally scalable crawler which facilitates high throughput and focused crawling of documents pertinent to a particular domain such as information about polar regions. With this set of highly domain relevant documents, we show that it is possible to answer analytical questions about that domain. Our domain discovery algorithm leverages prior domain knowledge to reach out to commercial/scientific search engines to generate seed URLs. Subject matter experts then annotate these seed URLs manually on a scale from highly relevant to irrelevant. We leverage this annotated dataset to train a machine learning model which predicts the `domain relevance' of a given document. We extend Sparkler with this model to focus crawling on documents relevant to that domain. Sparkler avoids disruption of service by 1) partitioning URLs by hostname such that every node gets a different host to crawl and by 2) inserting delays between subsequent requests. With an NSF-funded supercomputer Wrangler, we scaled our domain discovery pipeline to crawl about 200k polar specific documents from the scientific web, within a day.

  6. The voltage-sensing domain of a phosphatase gates the pore of a potassium channel.

    Science.gov (United States)

    Arrigoni, Cristina; Schroeder, Indra; Romani, Giulia; Van Etten, James L; Thiel, Gerhard; Moroni, Anna

    2013-03-01

    The modular architecture of voltage-gated K(+) (Kv) channels suggests that they resulted from the fusion of a voltage-sensing domain (VSD) to a pore module. Here, we show that the VSD of Ciona intestinalis phosphatase (Ci-VSP) fused to the viral channel Kcv creates Kv(Synth1), a functional voltage-gated, outwardly rectifying K(+) channel. Kv(Synth1) displays the summed features of its individual components: pore properties of Kcv (selectivity and filter gating) and voltage dependence of Ci-VSP (V(1/2) = +56 mV; z of ~1), including the depolarization-induced mode shift. The degree of outward rectification of the channel is critically dependent on the length of the linker more than on its amino acid composition. This highlights a mechanistic role of the linker in transmitting the movement of the sensor to the pore and shows that electromechanical coupling can occur without coevolution of the two domains.

  7. Blocking-resistant communication through domain fronting

    Directory of Open Access Journals (Sweden)

    Fifield David

    2015-06-01

    Full Text Available We describe “domain fronting,” a versatile censorship circumvention technique that hides the remote endpoint of a communication. Domain fronting works at the application layer, using HTTPS, to communicate with a forbidden host while appearing to communicate with some other host, permitted by the censor. The key idea is the use of different domain names at different layers of communication. One domain appears on the “outside” of an HTTPS request—in the DNS request and TLS Server Name Indication—while another domain appears on the “inside”—in the HTTP Host header, invisible to the censor under HTTPS encryption. A censor, unable to distinguish fronted and nonfronted traffic to a domain, must choose between allowing circumvention traffic and blocking the domain entirely, which results in expensive collateral damage. Domain fronting is easy to deploy and use and does not require special cooperation by network intermediaries. We identify a number of hard-to-block web services, such as content delivery networks, that support domain-fronted connections and are useful for censorship circumvention. Domain fronting, in various forms, is now a circumvention workhorse. We describe several months of deployment experience in the Tor, Lantern, and Psiphon circumvention systems, whose domain-fronting transports now connect thousands of users daily and transfer many terabytes per month.

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Magnetic scanning gate microscopy of a domain wall nanosensor using microparticle probe

    Energy Technology Data Exchange (ETDEWEB)

    Corte-León, H., E-mail: hector.corte@npl.co.uk [National Physical Laboratory, Teddington TW11 0LW (United Kingdom); Royal Holloway University of London, Egham TW20 0EX (United Kingdom); Gribkov, B. [National Physical Laboratory, Teddington TW11 0LW (United Kingdom); Krzysteczko, P. [Physikalisch-Technische Bundesanstalt, Braunschweig D-38116 (Germany); Marchi, F.; Motte, J.-F. [University of Grenoble Alpes, Inst. NEEL, Grenoble F-38042 (France); CNRS, Inst. NEEL, Grenoble F-38042 (France); Schumacher, H.W. [Physikalisch-Technische Bundesanstalt, Braunschweig D-38116 (Germany); Antonov, V. [Royal Holloway University of London, Egham TW20 0EX (United Kingdom); Kazakova, O. [National Physical Laboratory, Teddington TW11 0LW (United Kingdom)

    2016-02-15

    We apply the magnetic scanning gate microscopy (SGM) technique to study the interaction between a magnetic bead (MB) and a domain wall (DW) trapped in an L-shaped magnetic nanostructure. Magnetic SGM is performed using a custom-made probe, comprising a hard magnetic NdFeB bead of diameter 1.6 µm attached to a standard silicon tip. The MB–DW interaction is detected by measuring changes in the electrical resistance of the device as a function of the tip position. By scanning at different heights, we create a 3D map of the MB–DW interaction and extract the sensing volume for different widths of the nanostructure's arms. It is shown that for 50 nm wide devices the sensing volume is a cone of 880 nm in diameter by 1.4 µm in height, and reduces down to 800 nm in height for 100 nm devices with almost no change in its diameter. - Highlights: • AFM tips with a magnetic bead attached used to test interaction with domain wall. • Domain wall inside a nanostructure affect the electrical resistance. • Recording electrical resistance while scanning with modified AFM probe. • Change of resistance as a function of the position of the magnetic bead. • This allows comparing different devices in a reproducible and controllable way.

  10. Negative density dependence of sympatric Hinge-back Tortoises (Kinixys erosa and K. homeana in West Africa

    Directory of Open Access Journals (Sweden)

    Luca Luiselli

    2008-05-01

    Full Text Available A series of 59 transect surveys was conducted in selected wet forest habitats, along the coast of West Africa, to estimate the density distribution of African Hinge-back tortoises (Kinixys homeana and K. erosa. Line transect data were fed into a simple model to derive a detection function. The parameters estimated by the model produced an elaborate characterisation of tortoise distribution, which proved to be useful in the formulation of hypotheses about tortoise densities. Line transect data were analysed by DISTANCE, with a series of key and the series adjustment: the uniform function, the 1-parameter half-normal function, and the 2-parameter hazard-rate function were considered as key functions; the cosine series, simple polynomials, and Hermite polynomials were considered as series expansions. The detection function was estimated separately for Kinixys homeana and K. erosa, and for transects grouped for each study area by considering all the combinations of the above key functions and series expansions. The Akaike Information Criterion (AIC was computed for each candidate model and used for model selection. The best model of the detection function, for both the tortoise species was the uniform function with no series expansion. Model results indicated that the density of the two species was inversely related at the local scale, and complementary across the region; such that the density of one species increases from West to East while the other one declines. Overall, the comparison of density estimates between the two tortoises is consistent with a former hypothesis suggesting inter-specific competition and consequent resource partitioning. Other causes may contribute to explain the observed patterns, including the low productivity of rainforest habitats and long-term human perturbation.

  11. An ontological approach to domain engineering

    NARCIS (Netherlands)

    Falbo, R.A.; Guizzardi, G.; Duarte, K.

    2002-01-01

    Domain engineering aims to support systematic reuse, focusing on modeling common knowledge in a problem domain. Ontologies have also been pointed as holding great promise for software reuse. In this paper, we present ODE (Ontology-based Domain Engineering), an ontological approach for domain

  12. Role of the vaccinia virus O3 protein in cell entry can be fulfilled by its Sequence flexible transmembrane domain

    Energy Technology Data Exchange (ETDEWEB)

    Satheshkumar, P.S.; Chavre, James; Moss, Bernard, E-mail: bmoss@nih.gov

    2013-09-15

    The vaccinia virus O3 protein, a component of the entry–fusion complex, is encoded by all chordopoxviruses. We constructed truncation mutants and demonstrated that the transmembrane domain, which comprises two-thirds of this 35 amino acid protein, is necessary and sufficient for interaction with the entry–fusion complex and function in cell entry. Nevertheless, neither single amino acid substitutions nor alanine scanning mutagenesis revealed essential amino acids within the transmembrane domain. Moreover, replication-competent mutant viruses were generated by randomization of 10 amino acids of the transmembrane domain. Of eight unique viruses, two contained only two amino acids in common with wild type and the remainder contained one or none within the randomized sequence. Although these mutant viruses formed normal size plaques, the entry–fusion complex did not co-purify with the mutant O3 proteins suggesting a less stable interaction. Thus, despite low specific sequence requirements, the transmembrane domain is sufficient for function in entry. - Highlights: • The 35 amino acid O3 protein is required for efficient vaccinia virus entry. • The transmembrane domain of O3 is necessary and sufficient for entry. • Mutagenesis demonstrated extreme sequence flexibility compatible with function.

  13. The V domain of dog PVRL4 (nectin-4) mediates canine distemper virus entry and virus cell-to-cell spread

    International Nuclear Information System (INIS)

    Delpeut, Sebastien; Noyce, Ryan S.; Richardson, Christopher D.

    2014-01-01

    The entry of canine distemper virus (CDV) is a multistep process that involves the attachment of CDV hemagglutinin (H) to its cellular receptor, followed by fusion between virus and cell membranes. Our laboratory recently identified PVRL4 (nectin-4) to be the epithelial receptor for measles and canine distemper viruses. In this study, we demonstrate that the V domain of PVRL4 is critical for CDV entry and virus cell-to-cell spread. Furthermore, four key amino acid residues within the V domain of dog PVRL4 and two within the CDV hemagglutinin were shown to be essential for receptor-mediated virus entry. - Highlights: • PVRL4 (nectin-4) is the epithelial cell receptor for measles and canine distemper viruses. • V domain of PVRL4 is critical for CDV entry, cell-to-cell spread, and syncytia formation. • Chimeric PVRL1 backbone substituted with the V domain of PVRL4 can function as a receptor. • Amino acids (F132/P133/A134/G135) within the V domain are essential for PVRL4 receptor activity. • Amino acids (P493/Y539) within CDV H protein are essential for PVRL4 receptor interaction

  14. The V domain of dog PVRL4 (nectin-4) mediates canine distemper virus entry and virus cell-to-cell spread

    Energy Technology Data Exchange (ETDEWEB)

    Delpeut, Sebastien; Noyce, Ryan S. [The Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada B3H 1X5 (Canada); IWK Health Centre, Canadian Center for Vaccinology, Goldbloom Pavilion, Halifax, Nova Scotia, Canada B3H 1X5 (Canada); Richardson, Christopher D., E-mail: chris.richardson@dal.ca [The Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada B3H 1X5 (Canada); IWK Health Centre, Canadian Center for Vaccinology, Goldbloom Pavilion, Halifax, Nova Scotia, Canada B3H 1X5 (Canada); The Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia (Canada)

    2014-04-15

    The entry of canine distemper virus (CDV) is a multistep process that involves the attachment of CDV hemagglutinin (H) to its cellular receptor, followed by fusion between virus and cell membranes. Our laboratory recently identified PVRL4 (nectin-4) to be the epithelial receptor for measles and canine distemper viruses. In this study, we demonstrate that the V domain of PVRL4 is critical for CDV entry and virus cell-to-cell spread. Furthermore, four key amino acid residues within the V domain of dog PVRL4 and two within the CDV hemagglutinin were shown to be essential for receptor-mediated virus entry. - Highlights: • PVRL4 (nectin-4) is the epithelial cell receptor for measles and canine distemper viruses. • V domain of PVRL4 is critical for CDV entry, cell-to-cell spread, and syncytia formation. • Chimeric PVRL1 backbone substituted with the V domain of PVRL4 can function as a receptor. • Amino acids (F132/P133/A134/G135) within the V domain are essential for PVRL4 receptor activity. • Amino acids (P493/Y539) within CDV H protein are essential for PVRL4 receptor interaction.

  15. Ferroelectric negative capacitance domain dynamics

    Science.gov (United States)

    Hoffmann, Michael; Khan, Asif Islam; Serrao, Claudy; Lu, Zhongyuan; Salahuddin, Sayeef; Pešić, Milan; Slesazeck, Stefan; Schroeder, Uwe; Mikolajick, Thomas

    2018-05-01

    Transient negative capacitance effects in epitaxial ferroelectric Pb(Zr0.2Ti0.8)O3 capacitors are investigated with a focus on the dynamical switching behavior governed by domain nucleation and growth. Voltage pulses are applied to a series connection of the ferroelectric capacitor and a resistor to directly measure the ferroelectric negative capacitance during switching. A time-dependent Ginzburg-Landau approach is used to investigate the underlying domain dynamics. The transient negative capacitance is shown to originate from reverse domain nucleation and unrestricted domain growth. However, with the onset of domain coalescence, the capacitance becomes positive again. The persistence of the negative capacitance state is therefore limited by the speed of domain wall motion. By changing the applied electric field, capacitor area or external resistance, this domain wall velocity can be varied predictably over several orders of magnitude. Additionally, detailed insights into the intrinsic material properties of the ferroelectric are obtainable through these measurements. A new method for reliable extraction of the average negative capacitance of the ferroelectric is presented. Furthermore, a simple analytical model is developed, which accurately describes the negative capacitance transient time as a function of the material properties and the experimental boundary conditions.

  16. Functional domains of plant chimeric calcium/calmodulin-dependent protein kinase: regulation by autoinhibitory and visinin-like domains

    Science.gov (United States)

    Ramachandiran, S.; Takezawa, D.; Wang, W.; Poovaiah, B. W.

    1997-01-01

    A novel calcium-binding calcium/calmodulin-dependent protein kinase (CCaMK) with a catalytic domain, calmodulin-binding domain, and a neural visinin-like domain was cloned and characterized from plants [Patil et al., (1995) Proc. Natl. Acad. Sci. USA 92, 4797-4801; Takezawa et al. (1996) J. Biol. Chem. 271, 8126-8132]. The mechanisms of CCaMK activation by calcium and calcium/calmodulin were investigated using various deletion mutants. The use of deletion mutants of CCaMK lacking either one, two, or all three calcium-binding EF hands indicated that all three calcium-binding sites in the visinin-like domain were crucial for the full calcium/calmodulin-dependent kinase activity. As each calcium-binding EF hand was deleted, there was a gradual reduction in calcium/calmodulin-dependent kinase activity from 100 to 4%. Another mutant (amino acids 1-322) which lacks both the visinin-like domain containing three EF hands and the calmodulin-binding domain was constitutively active, indicating the presence of an autoinhibitory domain around the calmodulin-binding domain. By using various synthetic peptides and the constitutively active mutant, we have shown that CCaMK contains an autoinhibitory domain within the residues 322-340 which overlaps its calmodulin-binding domain. Kinetic studies with both ATP and the GS peptide substrate suggest that the autoinhibitory domain of CCaMK interacts only with the peptide substrate binding motif of the catalytic domain, but not with the ATP-binding motif.

  17. Summarization by domain ontology navigation

    DEFF Research Database (Denmark)

    Andreasen, Troels; Bulskov, Henrik

    2013-01-01

    of the subject. In between these two extremes, conceptual summaries encompass selected concepts derived using background knowledge. We address in this paper an approach where conceptual summaries are provided through a conceptualization as given by an ontology. The ontology guiding the summarization can...... be a simple taxonomy or a generative domain ontology. A domain ontology can be provided by a preanalysis of a domain corpus and can be used to condense improved summaries that better reflects the conceptualization of a given domain....

  18. 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...

  19. Domain-specific languages in perspective

    NARCIS (Netherlands)

    J. Heering (Jan); M. Mernik (Marjan)

    2007-01-01

    textabstractDomain-specific languages (DSLs) are languages tailored to a specific application domain. They offer substantial gains in expressiveness and ease of use compared with general-purpose languages in their domain of application. Although the use of DSLs is by no means new, it is receiving

  20. Detecting atypical examples of known domain types by sequence similarity searching: the SBASE domain library approach.

    Science.gov (United States)

    Dhir, Somdutta; Pacurar, Mircea; Franklin, Dino; Gáspári, Zoltán; Kertész-Farkas, Attila; Kocsor, András; Eisenhaber, Frank; Pongor, Sándor

    2010-11-01

    SBASE is a project initiated to detect known domain types and predicting domain architectures using sequence similarity searching (Simon et al., Protein Seq Data Anal, 5: 39-42, 1992, Pongor et al, Nucl. Acids. Res. 21:3111-3115, 1992). The current approach uses a curated collection of domain sequences - the SBASE domain library - and standard similarity search algorithms, followed by postprocessing which is based on a simple statistics of the domain similarity network (http://hydra.icgeb.trieste.it/sbase/). It is especially useful in detecting rare, atypical examples of known domain types which are sometimes missed even by more sophisticated methodologies. This approach does not require multiple alignment or machine learning techniques, and can be a useful complement to other domain detection methodologies. This article gives an overview of the project history as well as of the concepts and principles developed within this the project.

  1. Brookhaven highlights, October 1979-September 1980

    International Nuclear Information System (INIS)

    1980-01-01

    Highlights are given for the research areas of the Brookhaven National Laboratory. These areas include high energy physics, physics and chemistry, life sciences, applied energy science (energy and environment, and nuclear energy), and support activities (including mathematics, instrumentation, reactors, and safety)

  2. 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.

  3. 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

  4. Pathogenic Parkinson's disease mutations across the functional domains of LRRK2 alter the autophagic/lysosomal response to starvation.

    Science.gov (United States)

    Manzoni, Claudia; Mamais, Adamantios; Dihanich, Sybille; McGoldrick, Phillip; Devine, Michael J; Zerle, Julia; Kara, Eleanna; Taanman, Jan-Willem; Healy, Daniel G; Marti-Masso, Jose-Felix; Schapira, Anthony H; Plun-Favreau, Helene; Tooze, Sharon; Hardy, John; Bandopadhyay, Rina; Lewis, Patrick A

    2013-11-29

    LRRK2 is one of the most important genetic contributors to Parkinson's disease (PD). Point mutations in this gene cause an autosomal dominant form of PD, but to date no cellular phenotype has been consistently linked with mutations in each of the functional domains (ROC, COR and Kinase) of the protein product of this gene. In this study, primary fibroblasts from individuals carrying pathogenic mutations in the three central domains of LRRK2 were assessed for alterations in the autophagy/lysosomal pathway using a combination of biochemical and cellular approaches. Mutations in all three domains resulted in alterations in markers for autophagy/lysosomal function compared to wild type cells. These data highlight the autophagy and lysosomal pathways as read outs for pathogenic LRRK2 function and as a marker for disease, and provide insight into the mechanisms linking LRRK2 function and mutations. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Highlights 2005

    International Nuclear Information System (INIS)

    2006-02-01

    This document summarizes a year of activities for the ESRF (European synchrotron radiation facilities), this facility serves 31 beamlines that represent 34 end stations that can be run independently. This document is organized into 9 parts. Part 1: 'high resolution and resonance scattering' deals with surface science and magnetism at high pressure, in particular results are presented for samarium and europium chalcogenides. A cross-section of a variety of applications are presented, they range from glass physics to the understanding of thermoelectric materials. Part 2: 'materials sciences' deals with material behaviour under extreme conditions (metallic sulfur above 100 GPa,...) general applications of X-ray diffraction : stress and strain studies, assessment of excess free volume in metallic glasses, or grain nucleation and growth kinetics during solidification. Part 3: 'soft condensed matter'. Part 4: 'structural biology'. Part 5: 'surface and interface science' (at ESRF surfaces and interfaces are studied at about 50% of all beamlines). A study shows the existence of ordered SiGe domains in the interior of the small Ge islands in Si, whereas bulk SiGe alloy is disordered. Other studies shed light on the surprisingly different magnetic behaviour of ultra-thin cobalt and nickel films on a platinum surface. Part 6 : 'X-ray absorption and magnetic scattering'. Many of the studies push the limits of methods using high pressure, high magnetic fields, high and low temperature with absorption and scattering techniques. There are also examples of measurements on the femtosecond time scale using the core-hole clock method and on femto-meter length scale in magnetostriction measurements. Part 7: 'X-ray imaging and optics'. Part 8: 'the X-ray source'. Part 9: 'facts and figures'. (A.C.)

  6. Highlights 2005

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2006-02-15

    This document summarizes a year of activities for the ESRF (European synchrotron radiation facilities), this facility serves 31 beamlines that represent 34 end stations that can be run independently. This document is organized into 9 parts. Part 1: 'high resolution and resonance scattering' deals with surface science and magnetism at high pressure, in particular results are presented for samarium and europium chalcogenides. A cross-section of a variety of applications are presented, they range from glass physics to the understanding of thermoelectric materials. Part 2: 'materials sciences' deals with material behaviour under extreme conditions (metallic sulfur above 100 GPa,...) general applications of X-ray diffraction : stress and strain studies, assessment of excess free volume in metallic glasses, or grain nucleation and growth kinetics during solidification. Part 3: 'soft condensed matter'. Part 4: 'structural biology'. Part 5: 'surface and interface science' (at ESRF surfaces and interfaces are studied at about 50% of all beamlines). A study shows the existence of ordered SiGe domains in the interior of the small Ge islands in Si, whereas bulk SiGe alloy is disordered. Other studies shed light on the surprisingly different magnetic behaviour of ultra-thin cobalt and nickel films on a platinum surface. Part 6 : 'X-ray absorption and magnetic scattering'. Many of the studies push the limits of methods using high pressure, high magnetic fields, high and low temperature with absorption and scattering techniques. There are also examples of measurements on the femtosecond time scale using the core-hole clock method and on femto-meter length scale in magnetostriction measurements. Part 7: 'X-ray imaging and optics'. Part 8: 'the X-ray source'. Part 9: 'facts and figures'. (A.C.)

  7. The pH-sensitive structure of the C-terminal domain of voltage-gated proton channel and the thermodynamic characteristics of Zn{sup 2+} binding to this domain

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Qing; Li, Chuanyong; Li, Shu Jie, E-mail: shujieli@nankai.edu.cn

    2015-01-02

    Highlights: • The α-helical content of the C-terminus is decreased with a pH increase. • The thermostability of the C-terminus is decreased with a pH increase. • Zn{sup 2+} binds to His{sup 244} and His{sup 266} residues within the C-terminal domain. • The binding of Zn{sup 2+} to His{sup 244} residue is an endothermic heat reaction. • The binding of Zn{sup 2+} to His{sup 266} residue is an exothermic heat reaction. - Abstract: The voltage-gated proton channel Hv1 is strongly sensitive to Zn{sup 2+}. The H{sup +} conduction is decreased at a high concentration of Zn{sup 2+} and Hv1 channel closing is slowed by the internal application of Zn{sup 2+}. Although the recent studies demonstrated that Zn{sup 2+} interacts with the intracellular C-terminal domain, the binding sites and details of the interaction remain unknown. Here, we studied the pH-dependent structural stability of the intracellular C-terminal domain of human Hv1 and showed that Zn{sup 2+} binds to His{sup 244} and His{sup 266} residues. The thermodynamics signature of Zn{sup 2+} binding to the two sites was investigated by isothermal titration calorimetry. The binding of Zn{sup 2+} to His{sup 244} (mutant H266A) and His{sup 266} (mutant H244A) were an endothermic heat reaction and an exothermic heat reaction, respectively.

  8. The Structure of Urease Activation Complexes Examined by Flexibility Analysis, Mutagenesis, and Small-angle X-ray Scattering Approaches

    International Nuclear Information System (INIS)

    Quiroz, Soledad; Sukuru, Sai Chetan K.; Hausinger, Robert P.; Kuhn, Leslie A.; Heller, William T

    2008-01-01

    Conformational changes of Klebsiella aerogenes urease apoprotein (UreABC) 3 induced upon binding of the UreD and UreF accessory proteins were examined by a combination of flexibility analysis, mutagenesis, and small-angle X-ray scattering (SAXS). ProFlex analysis of urease provided evidence that the major domain of UreB can move in a hinge-like motion to account for prior chemical cross-linking results. Rigidification of the UreB hinge region, accomplished through a G11P mutation, reduced the extent of urease activation, in part by decreasing the nickel content of the mutant enzyme, and by sequestering a portion of the urease apoprotein in a novel activation complex that includes all of the accessory proteins. SAXS analyses of urease, (UreABC-UreD) 3 , and (UreABC-UreDF) 3 confirm that UreD and UreF bind near UreB at the periphery of the (UreAC) 3 structure. This study supports an activation model in which a domain-shifted UreB conformation in (UreABC-UreDF) 3 allows CO 2 and nickel ions to gain access to the nascent active site

  9. The neural signature of self-concept development in adolescence: The role of domain and valence distinctions

    Directory of Open Access Journals (Sweden)

    R. van der Cruijsen

    2018-04-01

    Full Text Available Neuroimaging studies in adults showed that cortical midline regions including medial prefrontal cortex (mPFC and posterior parietal cortex (PPC are important in self-evaluations. The goals of this study were to investigate the contribution of these regions to self-evaluations in late childhood, adolescence, and early adulthood, and to examine whether these differed per domain (academic, physical and prosocial and valence (positive versus negative. Also, we tested whether this activation changes across adolescence. For this purpose, participants between ages 11–21-years (N = 150 evaluated themselves on trait sentences in an fMRI session. Behaviorally, adolescents rated their academic traits less positively than children and young adults. The neural analyses showed that evaluating self-traits versus a control condition was associated with increased activity in mPFC (domain-general effect, and positive traits were associated with increased activity in ventral mPFC (valence effect. Self-related mPFC activation increased linearly with age, but only for evaluating physical traits. Furthermore, an adolescent-specific decrease in striatum activation for positive self traits was found. Finally, we found domain-specific neural activity for evaluating traits in physical (dorsolateral PFC, dorsal mPFC and academic (PPC domains. Together, these results highlight the importance of domain distinctions when studying self-concept development in late childhood, adolescence, and early adulthood. Keywords: Self, fMRI, Adolescence, Development, Medial prefrontal cortex, Self-concept

  10. Exploring the research domain of consultant practice: Perceptions and opinions of consultant radiographers

    International Nuclear Information System (INIS)

    Harris, R.; Paterson, A.

    2016-01-01

    Aim: This paper reports on one part of a larger study. The aim was to explore what the core domain of research means to consultant radiographers in clinical practice and to identify the key factors that facilitate or hinder research activity by this staff group. Design and method: Grounded theory research methodology was employed. This first part of the study involved electronic questionnaires being sent to all those known in consultant radiographer posts in the United Kingdom. Results: Results indicate there are variations across clinical specialties as to the amount and level of research undertaken by consultant radiographers, and not all agreed that research should be a core domain of consultant practice. Main facilitators to research were noted as: time; skills and knowledge of the researcher; a well defined research question. Main barriers to research were noted as: lack of allocated time; lack of skills/experience; clinical workload. Conclusion: Research is one of the four core domains of consultant allied health professional and nursing roles but, as yet, it is not fully embedded into those of all consultant radiographers. Many consultant radiographers appear to spend more of their time on the ‘clinical expert’ element of their role at the expense of the research domain. This study concludes that there is an urgent need for consultant radiographers to understand that research is one of the four core domains and to recognise the need to embed research into their clinical practice. - Highlights: • Consultant radiographers undertake research but have concerns about their research skills. • Research aims to improve practice and patients' experiences. • Relatively few consultant radiographers publish their work routinely. • Consultant radiographers allocate little protected time for research due to clinical demands. • Almost half of the consultant radiographers feel research should not be a core part of their roles.

  11. A Highly Accurate Regular Domain Collocation Method for Solving Potential Problems in the Irregular Doubly Connected Domains

    Directory of Open Access Journals (Sweden)

    Zhao-Qing Wang

    2014-01-01

    Full Text Available Embedding the irregular doubly connected domain into an annular regular region, the unknown functions can be approximated by the barycentric Lagrange interpolation in the regular region. A highly accurate regular domain collocation method is proposed for solving potential problems on the irregular doubly connected domain in polar coordinate system. The formulations of regular domain collocation method are constructed by using barycentric Lagrange interpolation collocation method on the regular domain in polar coordinate system. The boundary conditions are discretized by barycentric Lagrange interpolation within the regular domain. An additional method is used to impose the boundary conditions. The least square method can be used to solve the overconstrained equations. The function values of points in the irregular doubly connected domain can be calculated by barycentric Lagrange interpolation within the regular domain. Some numerical examples demonstrate the effectiveness and accuracy of the presented method.

  12. Cytoplasmic tail domain of glycoprotein B is essential for HHV-6 infection

    Energy Technology Data Exchange (ETDEWEB)

    Mahmoud, Nora F. [Division of Clinical Virology, Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe (Japan); Faculty of Pharmacy, Suez Canal University, Ismailia (Egypt); Jasirwan, Chyntia [Division of Clinical Virology, Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe (Japan); Division of Hepatobiliary, Department of Internal Medicine, Faculty of Medicine, University of Indonesia (Indonesia); Kanemoto, Satoshi; Wakata, Aika; Wang, Bochao; Hata, Yuuki [Division of Clinical Virology, Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe (Japan); Nagamata, Satoshi [Division of Clinical Virology, Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe (Japan); Department of Obstetrics and Gynecology, Kobe University Graduate School of Medicine, Kobe (Japan); Kawabata, Akiko [Division of Clinical Virology, Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe (Japan); Tang, Huamin [Division of Clinical Virology, Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe (Japan); Department of Immunology, Nanjing Medical University, Nanjing (China); Mori, Yasuko, E-mail: ymori@med.kobe-u.ac.jp [Division of Clinical Virology, Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe (Japan)

    2016-03-15

    Human herpesvirus 6 (HHV-6) glycoprotein B (gB) is an abundantly expressed viral glycoprotein required for viral entry and cell fusion, and is highly conserved among herpesviruses. The present study examined the function of HHV-6 gB cytoplasmic tail domain (CTD). A gB CTD deletion mutant was constructed which, in contrast to its revertant, could not be reconstituted. Moreover, deletion of gB cytoplasmic tail impaired the intracellular transport of gB protein to the trans-Golgi network (TGN). Taken together, these results suggest that gB CTD is critical for HHV-6 propagation and important for intracellular transportation. - Highlights: • Glycoprotein B (gB) is highly conserved among herpesviruses. • HHV-6 gB is also abundantly expressed in virions. • In the present study, we showed the function of HHV-6 gB cytoplasmic tail domain (CTD). • We found that deletion of gB CTD impairs the intracellular transport of gB protein to the trans-Golgi network (TGN), and CTD of gB is critical for HHV-6 propagation.

  13. Cytoplasmic tail domain of glycoprotein B is essential for HHV-6 infection

    International Nuclear Information System (INIS)

    Mahmoud, Nora F.; Jasirwan, Chyntia; Kanemoto, Satoshi; Wakata, Aika; Wang, Bochao; Hata, Yuuki; Nagamata, Satoshi; Kawabata, Akiko; Tang, Huamin; Mori, Yasuko

    2016-01-01

    Human herpesvirus 6 (HHV-6) glycoprotein B (gB) is an abundantly expressed viral glycoprotein required for viral entry and cell fusion, and is highly conserved among herpesviruses. The present study examined the function of HHV-6 gB cytoplasmic tail domain (CTD). A gB CTD deletion mutant was constructed which, in contrast to its revertant, could not be reconstituted. Moreover, deletion of gB cytoplasmic tail impaired the intracellular transport of gB protein to the trans-Golgi network (TGN). Taken together, these results suggest that gB CTD is critical for HHV-6 propagation and important for intracellular transportation. - Highlights: • Glycoprotein B (gB) is highly conserved among herpesviruses. • HHV-6 gB is also abundantly expressed in virions. • In the present study, we showed the function of HHV-6 gB cytoplasmic tail domain (CTD). • We found that deletion of gB CTD impairs the intracellular transport of gB protein to the trans-Golgi network (TGN), and CTD of gB is critical for HHV-6 propagation.

  14. Context Influences on the Subjective Experience of Aging: The Impact of Culture and Domains of Functioning.

    Science.gov (United States)

    O'Brien, Erica L; Hess, Thomas M; Kornadt, Anna E; Rothermund, Klaus; Fung, Helene; Voss, Peggy

    2017-08-01

    Attitudes about aging influence how people feel about their aging and affect psychological and health outcomes in later life. Given cross-cultural variability in such attitudes, the subjective experience of aging (e.g., subjective age [SA]) may also vary, potentially accounting for culture-specific patterns of aging-related outcomes. Our study explored cultural variation in SA and its determinants. American (N = 569), Chinese (N = 492), and German (N = 827) adults aged 30-95 years completed a questionnaire that included instruments measuring basic demographic information, SA, beliefs about thresholds of old age, control over life changes, and age dependency of changes in eight different life domains (i.e., family, work). Analyses revealed consistency across cultures in the domain-specificity of SA, but differences in the amount of shared variance across domains (e.g., Chinese adults exhibited greater homogeneity across domains than did Americans and Germans). Cultural differences were also observed in levels of SA in some domains, which were attenuated by domain-specific beliefs (e.g., control). Interestingly, beliefs about aging accounted for more cultural variation in SA than did sociodemographic factors (e.g., education). Our results demonstrate that subjective perceptions of aging and everyday functioning may be best understood from a perspective focused on context (i.e., culture, life domain). Given its important relation to functioning, examination of cross-cultural differences in the subjective experience of aging may highlight factors that determine variations in aging-related outcomes that then could serve as targets of culture-specific interventions promoting well-being in later life. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  15. University of Maryland MRSEC - Research: Highlights

    Science.gov (United States)

    -Engineering Program: Project Lead the Way Thinking Small: Nanoscale Informal Science Education (NISE Education Outreach Highlights NanoFabulous Greatest Show on Earth: Big Top Physics, USA Science and Perspective at UMD MRSEC Nanoscience Camp Annual Middle School Student Science Conference (SSC) Pre

  16. Brookhaven highlights, October 1979-September 1980

    Energy Technology Data Exchange (ETDEWEB)

    1980-01-01

    Highlights are given for the research areas of the Brookhaven National Laboratory. These areas include high energy physics, physics and chemistry, life sciences, applied energy science (energy and environment, and nuclear energy), and support activities (including mathematics, instrumentation, reactors, and safety). (GHT)

  17. Brookhaven highlights - Brookhaven National Laboratory 1995

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-09-01

    This report highlights research conducted at Brookhaven National Laboratory in the following areas: alternating gradient synchrotron; physics; biology; national synchrotron light source; department of applied science; medical; chemistry; department of advanced technology; reactor; safety and environmental protection; instrumentation; and computing and communications.

  18. Highlights of nuclear chemistry 1994

    International Nuclear Information System (INIS)

    1994-12-01

    Highlights were: 1. Fission product release: benchmark calculations for severe nuclear accidents; 2. Thermochemical data for reactor materials and fission products; 3. thermochemical calculations on fuel of the high-temperature gas-cooled reactor; 4. Formation of organic tellurides during nuclear accidents?; 5. Reaction of tellurium with Zircaloy-4; 6. Transmutation of fission products; 7. The thermal conductivity of high-burnup UO 2 fuel; 8. Tritium retention in graphite. (orig./HP)

  19. Structure and dynamics of the human pleckstrin DEP domain: distinct molecular features of a novel DEP domain subfamily.

    Science.gov (United States)

    Civera, Concepcion; Simon, Bernd; Stier, Gunter; Sattler, Michael; Macias, Maria J

    2005-02-01

    Pleckstrin1 is a major substrate for protein kinase C in platelets and leukocytes, and comprises a central DEP (disheveled, Egl-10, pleckstrin) domain, which is flanked by two PH (pleckstrin homology) domains. DEP domains display a unique alpha/beta fold and have been implicated in membrane binding utilizing different mechanisms. Using multiple sequence alignments and phylogenetic tree reconstructions, we find that 6 subfamilies of the DEP domain exist, of which pleckstrin represents a novel and distinct subfamily. To clarify structural determinants of the DEP fold and to gain further insight into the role of the DEP domain, we determined the three-dimensional structure of the pleckstrin DEP domain using heteronuclear NMR spectroscopy. Pleckstrin DEP shares main structural features with the DEP domains of disheveled and Epac, which belong to different DEP subfamilies. However, the pleckstrin DEP fold is distinct from these structures and contains an additional, short helix alpha4 inserted in the beta4-beta5 loop that exhibits increased backbone mobility as judged by NMR relaxation measurements. Based on sequence conservation, the helix alpha4 may also be present in the DEP domains of regulator of G-protein signaling (RGS) proteins, which are members of the same DEP subfamily. In pleckstrin, the DEP domain is surrounded by two PH domains. Structural analysis and charge complementarity suggest that the DEP domain may interact with the N-terminal PH domain in pleckstrin. Phosphorylation of the PH-DEP linker, which is required for pleckstrin function, could regulate such an intramolecular interaction. This suggests a role of the pleckstrin DEP domain in intramolecular domain interactions, which is distinct from the functions of other DEP domain subfamilies found so far.

  20. Structural insight in the inhibition of adherence of F4 fimbriae producing enterotoxigenic Escherichia coli by llama single domain antibodies.

    Science.gov (United States)

    Moonens, Kristof; Van den Broeck, Imke; Okello, Emmanuel; Pardon, Els; De Kerpel, Maia; Remaut, Han; De Greve, Henri

    2015-02-24

    Enterotoxigenic Escherichia coli that cause neonatal and post-weaning diarrhea in piglets express F4 fimbriae to mediate attachment towards host receptors. Recently we described how llama single domain antibodies (VHHs) fused to IgA, produced in Arabidopsis thaliana seeds and fed to piglets resulted in a progressive decline in shedding of F4 positive ETEC bacteria. Here we present the structures of these inhibiting VHHs in complex with the major adhesive subunit FaeG. A conserved surface, distant from the lactose binding pocket, is targeted by these VHHs, highlighting the possibility of targeting epitopes on single-domain adhesins that are non-involved in receptor binding.