Sample records for functional protein hinge
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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.
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NASA Astrophysics Data System (ADS)
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.
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Computational prediction of hinge axes in proteins
2014-01-01
Background A protein's function is determined by the wide range of motions exhibited by its 3D structure. However, current experimental techniques are not able to reliably provide the level of detail required for elucidating the exact mechanisms of protein motion essential for effective drug screening and design. Computational tools are instrumental in the study of the underlying structure-function relationship. We focus on a special type of proteins called "hinge proteins" which exhibit a motion that can be interpreted as a rotation of one domain relative to another. Results This work proposes a computational approach that uses the geometric structure of a single conformation to predict the feasible motions of the protein and is founded in recent work from rigidity theory, an area of mathematics that studies flexibility properties of general structures. Given a single conformational state, our analysis predicts a relative axis of motion between two specified domains. We analyze a dataset of 19 structures known to exhibit this hinge-like behavior. For 15, the predicted axis is consistent with a motion to a second, known conformation. We present a detailed case study for three proteins whose dynamics have been well-studied in the literature: calmodulin, the LAO binding protein and the Bence-Jones protein. Conclusions Our results show that incorporating rigidity-theoretic analyses can lead to effective computational methods for understanding hinge motions in macromolecules. This initial investigation is the first step towards a new tool for probing the structure-dynamics relationship in proteins. PMID:25080829
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Collective Dynamics of Periplasmic Glutamine Binding Protein upon Domain Closure
Loeffler, Hannes H.; Kitao, Akio
2009-01-01
The glutamine binding protein is a vital component of the associated ATP binding cassette transport systems responsible for the uptake of glutamine into the cell. We have investigated the global movements of this protein by molecular dynamics simulations and principal component analysis (PCA). We confirm that the most dominant mode corresponds to the biological function of the protein, i.e., a hinge-type motion upon ligand binding. The closure itself was directly observed from two independent trajectories whereby PCA was used to elucidate the nature of this closing reaction. Two intermediary states are identified and described in detail. The ligand binding induces the structural change of the hinge regions from a discontinuous β-sheet to a continuous one, which also enhances softness of the hinge and modifies the direction of hinge motion to enable closing. We also investigated the convergence behavior of PCA modes, which were found to converge rather quickly when the associated magnitudes of the eigenvalues are well separated. PMID:19883597
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Interconversion of Functional Motions between Mesophilic and Thermophilic Adenylate Kinases
Daily, Michael D.; Phillips, George N.; Cui, Qiang
2011-01-01
Dynamic properties are functionally important in many proteins, including the enzyme adenylate kinase (AK), for which the open/closed transition limits the rate of catalytic turnover. Here, we compare our previously published coarse-grained (double-well Gō) simulation of mesophilic AK from E. coli (AKmeso) to simulations of thermophilic AK from Aquifex aeolicus (AKthermo). In AKthermo, as with AKmeso, the LID domain prefers to close before the NMP domain in the presence of ligand, but LID rigid-body flexibility in the open (O) ensemble decreases significantly. Backbone foldedness in O and/or transition state (TS) ensembles increases significantly relative to AKmeso in some interdomain backbone hinges and within LID. In contact space, the TS of AKthermo has fewer contacts at the CORE-LID interface but a stronger contact network surrounding the CORE-NMP interface than the TS of AKmeso. A “heated” simulation of AKthermo at 375K slightly increases LID rigid-body flexibility in accordance with the “corresponding states” hypothesis. Furthermore, while computational mutation of 7 prolines in AKthermo to their AKmeso counterparts produces similar small perturbations, mutation of these sites, especially positions 8 and 155, to glycine is required to achieve LID rigid-body flexibility and hinge flexibilities comparable to AKmeso. Mutating the 7 sites to proline in AKmeso reduces some hinges' flexibilities, especially hinge 2, but does not reduce LID rigid-body flexibility, suggesting that these two types of motion are decoupled in AKmeso. In conclusion, our results suggest that hinge flexibility and global functional motions alike are correlated with but not exclusively determined by the hinge residues. This mutational framework can inform the rational design of functionally important flexibility and allostery in other proteins toward engineering novel biochemical pathways. PMID:21779157
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Hinge residue I174 is critical for proper dNTP selection by DNA polymerase beta.
Yamtich, Jen; Starcevic, Daniela; Lauper, Julia; Smith, Elenoe; Shi, Idina; Rangarajan, Sneha; Jaeger, Joachim; Sweasy, Joann B
2010-03-23
DNA polymerase beta (pol beta) is the key gap-filling polymerase in base excision repair, the DNA repair pathway responsible for repairing up to 20000 endogenous lesions per cell per day. Pol beta is also widely used as a model polymerase for structure and function studies, and several structural regions have been identified as being critical for the fidelity of the enzyme. One of these regions is the hydrophobic hinge, a network of hydrophobic residues located between the palm and fingers subdomains. Previous work by our lab has shown that hinge residues Y265, I260, and F272 are critical for polymerase fidelity by functioning in discrimination of the correct from incorrect dNTP during ground state binding. Our work aimed to elucidate the role of hinge residue I174 in polymerase fidelity. To study this residue, we conducted a genetic screen to identify mutants with a substitution at residue I174 that resulted in a mutator polymerase. We then chose the mutator mutant I174S for further study and found that it follows the same general kinetic pathway as and has an overall protein folding similar to that of wild-type (WT) pol beta. Using single-turnover kinetic analysis, we found that I174S exhibits decreased fidelity when inserting a nucleotide opposite a template base G, and this loss of fidelity is due primarily to a loss of discrimination during ground state dNTP binding. Molecular dynamics simulations show that mutation of residue I174 to serine results in an overall tightening of the hinge region, resulting in aberrant protein dynamics and fidelity. These results point to the hinge region as being critical in the maintenance of the proper geometry of the dNTP binding pocket.
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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.
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Morra, Giulia; Potestio, Raffaello; Micheletti, Cristian; Colombo, Giorgio
2012-01-01
Understanding how local protein modifications, such as binding small-molecule ligands, can trigger and regulate large-scale motions of large protein domains is a major open issue in molecular biology. We address various aspects of this problem by analyzing and comparing atomistic simulations of Hsp90 family representatives for which crystal structures of the full length protein are available: mammalian Grp94, yeast Hsp90 and E.coli HtpG. These chaperones are studied in complex with the natural ligands ATP, ADP and in the Apo state. Common key aspects of their functional dynamics are elucidated with a novel multi-scale comparison of their internal dynamics. Starting from the atomic resolution investigation of internal fluctuations and geometric strain patterns, a novel analysis of domain dynamics is developed. The results reveal that the ligand-dependent structural modulations mostly consist of relative rigid-like movements of a limited number of quasi-rigid domains, shared by the three proteins. Two common primary hinges for such movements are identified. The first hinge, whose functional role has been demonstrated by several experimental approaches, is located at the boundary between the N-terminal and Middle-domains. The second hinge is located at the end of a three-helix bundle in the Middle-domain and unfolds/unpacks going from the ATP- to the ADP-state. This latter site could represent a promising novel druggable allosteric site common to all chaperones. PMID:22457611
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Kikuchi, Y; Tamiya, N
1987-01-01
The proteins in the hinge ligaments of molluscan bivalves were subjected to chemotaxonomic studies according to their amino acid compositions. The hinge-ligament protein is a new class of structure proteins, and this is the first attempt to introduce chemical taxonomy into the systematics of bivalves. The hinge-ligament proteins from morphologically close species, namely mactra (superfamily Mactracea) or scallop (family Pectinidae) species, showed high intraspecific homology in their compositions. On the other hand, inconsistent results were obtained with two types of ligament proteins in pearl oyster species (genus Pinctada). The results of our chemotaxonomic analyses were sometimes in good agreement with the morphological classifications and sometimes inconsistent, implying a complicated phylogenetic relationship among the species. PMID:3593265
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Butrapet, Siritorn; Childers, Thomas; Moss, Kelley J.
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, butmore » 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.« less
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Engineering Upper Hinge Improves Stability and Effector Function of a Human IgG1
Yan, Boxu; Boyd, Daniel; Kaschak, Timothy; Tsukuda, Joni; Shen, Amy; Lin, Yuwen; Chung, Shan; Gupta, Priyanka; Kamath, Amrita; Wong, Anne; Vernes, Jean-Michel; Meng, Gloria Y.; Totpal, Klara; Schaefer, Gabriele; Jiang, Guoying; Nogal, Bartek; Emery, Craig; Vanderlaan, Martin; Carter, Paul; Harris, Reed; Amanullah, Ashraf
2012-01-01
Upper hinge is vulnerable to radical attacks that result in breakage of the heavy-light chain linkage and cleavage of the hinge of an IgG1. To further explore mechanisms responsible for the radical induced hinge degradation, nine mutants were designed to determine the roles that the upper hinge Asp and His play in the radical reactions. The observation that none of these substitutions could inhibit the breakage of the heavy-light chain linkage suggests that the breakage may result from electron transfer from Cys231 directly to the heavy-light chain linkage upon radical attacks, and implies a pathway separate from His229-mediated hinge cleavage. On the other hand, the substitution of His229 with Tyr showed promising advantages over the native antibody and other substitutions in improving the stability and function of the IgG1. This substitution inhibited the hinge cleavage by 98% and suggests that the redox active nature of Tyr did not enable it to replicate the ability of His to facilitate radical induced degradation. We propose that the lower redox potential of Tyr, a residue that may be the ultimate sink for oxidizing equivalents in proteins, is responsible for the inhibition. More importantly, the substitution increased the antibody's binding to FcγRIII receptors by 2–3-fold, and improved ADCC activity by 2-fold, while maintaining a similar pharmacokinetic profile with respect to the wild type. Implications of these observations for antibody engineering and development are discussed. PMID:22203673
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Engineering upper hinge improves stability and effector function of a human IgG1.
Yan, Boxu; Boyd, Daniel; Kaschak, Timothy; Tsukuda, Joni; Shen, Amy; Lin, Yuwen; Chung, Shan; Gupta, Priyanka; Kamath, Amrita; Wong, Anne; Vernes, Jean-Michel; Meng, Gloria Y; Totpal, Klara; Schaefer, Gabriele; Jiang, Guoying; Nogal, Bartek; Emery, Craig; Vanderlaan, Martin; Carter, Paul; Harris, Reed; Amanullah, Ashraf
2012-02-17
Upper hinge is vulnerable to radical attacks that result in breakage of the heavy-light chain linkage and cleavage of the hinge of an IgG1. To further explore mechanisms responsible for the radical induced hinge degradation, nine mutants were designed to determine the roles that the upper hinge Asp and His play in the radical reactions. The observation that none of these substitutions could inhibit the breakage of the heavy-light chain linkage suggests that the breakage may result from electron transfer from Cys(231) directly to the heavy-light chain linkage upon radical attacks, and implies a pathway separate from His(229)-mediated hinge cleavage. On the other hand, the substitution of His(229) with Tyr showed promising advantages over the native antibody and other substitutions in improving the stability and function of the IgG1. This substitution inhibited the hinge cleavage by 98% and suggests that the redox active nature of Tyr did not enable it to replicate the ability of His to facilitate radical induced degradation. We propose that the lower redox potential of Tyr, a residue that may be the ultimate sink for oxidizing equivalents in proteins, is responsible for the inhibition. More importantly, the substitution increased the antibody's binding to FcγRIII receptors by 2-3-fold, and improved ADCC activity by 2-fold, while maintaining a similar pharmacokinetic profile with respect to the wild type. Implications of these observations for antibody engineering and development are discussed.
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Kinetics of the LOV domain of ZEITLUPE determine its circadian function in Arabidopsis
Pudasaini, Ashutosh; Shim, Jae Sung; Song, Young Hun; Shi, Hua; Kiba, Takatoshi; Somers, David E; Imaizumi, Takato; Zoltowski, Brian D
2017-01-01
A LOV (Light, Oxygen, or Voltage) domain containing blue-light photoreceptor ZEITLUPE (ZTL) directs circadian timing by degrading clock proteins in plants. Functions hinge upon allosteric differences coupled to the ZTL photocycle; however, structural and kinetic information was unavailable. Herein, we tune the ZTL photocycle over two orders of magnitude. These variants reveal that ZTL complexes with targets independent of light, but dictates enhanced protein degradation in the dark. In vivo experiments definitively show photocycle kinetics dictate the rate of clock component degradation, thereby impacting circadian period. Structural studies demonstrate that photocycle dependent activation of ZTL depends on an unusual dark-state conformation of ZTL. Crystal structures of ZTL LOV domain confirm delineation of structural and kinetic mechanisms and identify an evolutionarily selected allosteric hinge differentiating modes of PAS/LOV signal transduction. The combined biochemical, genetic and structural studies provide new mechanisms indicating how PAS/LOV proteins integrate environmental variables in complex networks. DOI: http://dx.doi.org/10.7554/eLife.21646.001 PMID:28244872
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Understanding protein lids: kinetic analysis of active hinge mutants in triosephosphate isomerase.
Sun, J; Sampson, N S
1999-08-31
In previous work we tested what three amino acid sequences could serve as a protein hinge in triosephosphate isomerase [Sun, J., and Sampson, N. S. (1998) Protein Sci. 7, 1495-1505]. We generated a genetic library encoding all 8000 possible 3 amino acid combinations at the C-terminal hinge and selected for those combinations of amino acids that formed active mutants. These mutants were classified into six phylogenetic families. Two families resembled wild-type hinges, and four families represented new types of hinges. In this work, the kinetic characteristics and thermal stabilities of mutants representing each of these families were determined in order to understand what properties make an efficient protein hinge, and why all of the families are not observed in nature. From a steady-state kinetic analysis of our mutants, it is clear that the partitioning between protonation of intermediate to form product and intermediate release from the enzyme surface to form methylglyoxal (a decomposition product) is not affected. The two most impaired mutants undergo a change in rate-limiting step from enediol formation to dihydroxyacetone phosphate binding. Thus, it appears that k(cat)/K(m)'s are reduced relative to wild type as a result of slower Michaelis complex formation and dissociation, rather than increased loop opening speed.
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Breed, Ananya A; Gomes, Amanda; Roy, Binita Sur; Mahale, Smita D; Pathak, Bhakti R
2013-04-01
Human Prostate Secretory Protein of 94 amino acids (PSP94) has been shown to bind human CRISP-3 (cysteine-rich secretory protein 3) with very high affinity. CRISP-3 belongs to the CRISP family of proteins having a PR-1 (pathogenesis related protein 1) domain at its N-terminal and ion channel regulatory (ICR) domain at its C-terminal connected by a hinge region. Functional significance of this complex is not yet known. In order to identify the residues and/or regions involved in PSP94-CRISP-3 interaction, site-directed mutagenesis was employed. Effect of the mutations on the interaction was studied by co-immunoprecipitation (Co-IP). For PSP94, amino acids Y(3), F(4), P(56) and the C-terminal β-strand were found to be crucial for interacting with CRISP-3. A disulfide bond between the two domains of PSP94 (C(37)A-C(73)A) was also important for this interaction. In case of CRISP-3, the N-terminal domain alone could not maintain a strong interaction with PSP94 but it required presence of the hinge region and not the C-terminal domain. Apart from CRISP-3, CRISP-2 was also found to interact with human PSP94. Based on our findings the most likely model of PSP94-CRISP-3 complex has been proposed. The terminal β-strands of PSP94 contact the first α-helix and the hinge region of CRISP-3. Involvement of the hinge region of CRISPs in interaction with PSP94 may affect the domain movement of CRISPs essential for the ion-channel regulatory activity resulting in inhibition of this activity. Copyright © 2013 Elsevier B.V. All rights reserved.
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Matrix proteins of Nipah and Hendra viruses interact with beta subunits of AP-3 complexes.
Sun, Weina; McCrory, Thomas S; Khaw, Wei Young; Petzing, Stephanie; Myers, Terrell; Schmitt, Anthony P
2014-11-01
Paramyxoviruses and other negative-strand RNA viruses encode matrix proteins that coordinate the virus assembly process. The matrix proteins link the viral glycoproteins and the viral ribonucleoproteins at virus assembly sites and often recruit host machinery that facilitates the budding process. Using a co-affinity purification strategy, we have identified the beta subunit of the AP-3 adapter protein complex, AP3B1, as a binding partner for the M proteins of the zoonotic paramyxoviruses Nipah virus and Hendra virus. Binding function was localized to the serine-rich and acidic Hinge domain of AP3B1, and a 29-amino-acid Hinge-derived polypeptide was sufficient for M protein binding in coimmunoprecipitation assays. Virus-like particle (VLP) production assays were used to assess the relationship between AP3B1 binding and M protein function. We found that for both Nipah virus and Hendra virus, M protein expression in the absence of any other viral proteins led to the efficient production of VLPs in transfected cells, and this VLP production was potently inhibited upon overexpression of short M-binding polypeptides derived from the Hinge region of AP3B1. Both human and bat (Pteropus alecto) AP3B1-derived polypeptides were highly effective at inhibiting the production of VLPs. VLP production was also impaired through small interfering RNA (siRNA)-mediated depletion of AP3B1 from cells. These findings suggest that AP-3-directed trafficking processes are important for henipavirus particle production and identify a new host protein-virus protein binding interface that could become a useful target in future efforts to develop small molecule inhibitors to combat paramyxoviral infections. Henipaviruses cause deadly infections in humans, with a mortality rate of about 40%. Hendra virus outbreaks in Australia, all involving horses and some involving transmission to humans, have been a continuing problem. Nipah virus caused a large outbreak in Malaysia in 1998, killing 109 people, and smaller outbreaks have since occurred in Bangladesh and India. In this study, we have defined, for the first time, host factors that interact with henipavirus M proteins and contribute to viral particle assembly. We have also defined a new host protein-viral protein binding interface that can potentially be targeted for the inhibition of paramyxovirus infections. Copyright © 2014, American Society for Microbiology. All Rights Reserved.
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Matrix Proteins of Nipah and Hendra Viruses Interact with Beta Subunits of AP-3 Complexes
Sun, Weina; McCrory, Thomas S.; Khaw, Wei Young; Petzing, Stephanie; Myers, Terrell
2014-01-01
ABSTRACT Paramyxoviruses and other negative-strand RNA viruses encode matrix proteins that coordinate the virus assembly process. The matrix proteins link the viral glycoproteins and the viral ribonucleoproteins at virus assembly sites and often recruit host machinery that facilitates the budding process. Using a co-affinity purification strategy, we have identified the beta subunit of the AP-3 adapter protein complex, AP3B1, as a binding partner for the M proteins of the zoonotic paramyxoviruses Nipah virus and Hendra virus. Binding function was localized to the serine-rich and acidic Hinge domain of AP3B1, and a 29-amino-acid Hinge-derived polypeptide was sufficient for M protein binding in coimmunoprecipitation assays. Virus-like particle (VLP) production assays were used to assess the relationship between AP3B1 binding and M protein function. We found that for both Nipah virus and Hendra virus, M protein expression in the absence of any other viral proteins led to the efficient production of VLPs in transfected cells, and this VLP production was potently inhibited upon overexpression of short M-binding polypeptides derived from the Hinge region of AP3B1. Both human and bat (Pteropus alecto) AP3B1-derived polypeptides were highly effective at inhibiting the production of VLPs. VLP production was also impaired through small interfering RNA (siRNA)-mediated depletion of AP3B1 from cells. These findings suggest that AP-3-directed trafficking processes are important for henipavirus particle production and identify a new host protein-virus protein binding interface that could become a useful target in future efforts to develop small molecule inhibitors to combat paramyxoviral infections. IMPORTANCE Henipaviruses cause deadly infections in humans, with a mortality rate of about 40%. Hendra virus outbreaks in Australia, all involving horses and some involving transmission to humans, have been a continuing problem. Nipah virus caused a large outbreak in Malaysia in 1998, killing 109 people, and smaller outbreaks have since occurred in Bangladesh and India. In this study, we have defined, for the first time, host factors that interact with henipavirus M proteins and contribute to viral particle assembly. We have also defined a new host protein-viral protein binding interface that can potentially be targeted for the inhibition of paramyxovirus infections. PMID:25210190
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Alternative S2 Hinge Regions of the Myosin Rod Affect Myofibrillar Structure and Myosin Kinetics
DOE Office of Scientific and Technical Information (OSTI.GOV)
Miller, Mark S.; Dambacher, Corey M.; Knowles, Aileen F.
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 modifyingmore » 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.« less
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Temperature dependence of internal friction in enzyme reactions.
Rauscher, Anna Á; Simon, Zoltán; Szöllosi, Gergely J; Gráf, László; Derényi, Imre; Malnasi-Csizmadia, Andras
2011-08-01
Our aim was to elucidate the physical background of internal friction of enzyme reactions by investigating the temperature dependence of internal viscosity. By rapid transient kinetic methods, we directly measured the rate constant of trypsin 4 activation, which is an interdomain conformational rearrangement, as a function of temperature and solvent viscosity. We found that the apparent internal viscosity shows an Arrhenius-like temperature dependence, which can be characterized by the activation energy of internal friction. Glycine and alanine mutations were introduced at a single position of the hinge of the interdomain region to evaluate how the flexibility of the hinge affects internal friction. We found that the apparent activation energies of the conformational change and the internal friction are interconvertible parameters depending on the protein flexibility. The more flexible a protein was, the greater proportion of the total activation energy of the reaction was observed as the apparent activation energy of internal friction. Based on the coupling of the internal and external movements of the protein during its conformational change, we constructed a model that quantitatively relates activation energy, internal friction, and protein flexibility.
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Scaling and self-organized criticality in proteins I
Phillips, J. C.
2009-01-01
The complexity of proteins is substantially simplified by regarding them as archetypical examples of self-organized criticality (SOC). To test this idea and elaborate on it, this article applies the Moret–Zebende SOC hydrophobicity scale to the large-scale scaffold repeat protein of the HEAT superfamily, PR65/A. Hydrophobic plasticity is defined and used to identify docking platforms and hinges from repeat sequences alone. The difference between the MZ scale and conventional hydrophobicity scales reflects long-range conformational forces that are central to protein functionality. PMID:19218446
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Zhou, Ge; Liang, Feng-Xia; Romih, Rok; Wang, Zefang; Liao, Yi; Ghiso, Jorge; Luque-Garcia, Jose L.; Neubert, Thomas A.; Kreibich, Gert; Alonso, Miguel A.; Schaeren-Wiemers, Nicole; Sun, Tung-Tien
2012-01-01
The apical surface of mammalian bladder urothelium is covered by large (500–1000 nm) two-dimensional (2D) crystals of hexagonally packed 16-nm uroplakin particles (urothelial plaques), which play a role in permeability barrier function and uropathogenic bacterial binding. How the uroplakin proteins are delivered to the luminal surface is unknown. We show here that myelin-and-lymphocyte protein (MAL), a 17-kDa tetraspan protein suggested to be important for the apical sorting of membrane proteins, is coexpressed with uroplakins in differentiated urothelial cell layers. MAL depletion in Madin–Darby canine kidney cells did not affect, however, the apical sorting of uroplakins, but it decreased the rate by which uroplakins were inserted into the apical surface. Moreover, MAL knockout in vivo led to the accumulation of fusiform vesicles in mouse urothelial superficial umbrella cells, whereas MAL transgenic overexpression in vivo led to enhanced exocytosis and compensatory endocytosis, resulting in the accumulation of the uroplakin-degrading multivesicular bodies. Finally, although MAL and uroplakins cofloat in detergent-resistant raft fractions, they are associated with distinct plaque and hinge membrane subdomains, respectively. These data suggest a model in which 1) MAL does not play a role in the apical sorting of uroplakins; 2) the propensity of uroplakins to polymerize forming 16-nm particles and later large 2D crystals that behave as detergent-resistant (giant) rafts may drive their apical targeting; 3) the exclusion of MAL from the expanding 2D crystals of uroplakins explains the selective association of MAL with the hinge areas in the uroplakin-delivering fusiform vesicles, as well as at the apical surface; and 4) the hinge-associated MAL may play a role in facilitating the incorporation of the exocytic uroplakin vesicles into the corresponding hinge areas of the urothelial apical surface. PMID:22323295
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Deployment hinge using wraparound strips
NASA Technical Reports Server (NTRS)
Blanc, Eric
1992-01-01
Aerospatiale developed a new appendage deployment concept called AMEDE (French acronym for improvement of deployment mechanisms) with a view toward increased simplicity and functional reliability. This new concept, applicable to the deployment of any type of spaceborne appendage (in particular to solar arrays), enables deployment without synchronization or speed regulation devices. On the other hand, it requires the use of hinges with low driving or resistive torques. The AMEDE concept is compared with the conventional deployment concept. The conceptual and functional principles for the ADELE hinge are presented, as well as the hinges' main characteristics. The development status of both the AMEDE concept and the ADELE (French acronym for deployment hinge using wraparound strips) hinge are addressed.
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Sim, Jaehyun; Sim, Jun; Park, Eunsung; Lee, Julian
2015-06-01
Many proteins undergo large-scale motions where relatively rigid domains move against each other. The identification of rigid domains, as well as the hinge residues important for their relative movements, is important for various applications including flexible docking simulations. In this work, we develop a method for protein rigid domain identification based on an exhaustive enumeration of maximal rigid domains, the rigid domains not fully contained within other domains. The computation is performed by mapping the problem to that of finding maximal cliques in a graph. A minimal set of rigid domains are then selected, which cover most of the protein with minimal overlap. In contrast to the results of existing methods that partition a protein into non-overlapping domains using approximate algorithms, the rigid domains obtained from exact enumeration naturally contain overlapping regions, which correspond to the hinges of the inter-domain bending motion. The performance of the algorithm is demonstrated on several proteins. © 2015 Wiley Periodicals, Inc.
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AP-2α and AP-2β cooperatively orchestrate homeobox gene expression during branchial arch patterning.
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.
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Fallon, Justin R; McNally, Elizabeth M
2018-08-01
The extracellular matrix (ECM) plays key roles in normal and diseased skeletal and cardiac muscle. In healthy muscle the ECM is essential for transmitting contractile force, maintaining myofiber integrity and orchestrating cellular signaling. Duchenne Muscular Dystrophy (DMD) is caused by loss of dystrophin, a cytosolic protein that anchors a transmembrane complex and serves as a vital link between the actin cytoskeleton and the basal lamina. Loss of dystrophin leads to membrane fragility and impaired signaling, resulting in myofiber death and cycles of inflammation and regeneration. Fibrosis is also a cardinal feature of DMD. In this review, we will focus on two cases where understanding the normal function and regulation of ECM in muscle has led to the discovery of candidate therapeutics for DMD. Biglycan is a small leucine rich repeat ECM protein present as two glycoforms in muscle that have dramatically different functions. One widely expressed form is biglycan proteoglycan (PG) that bears two chondroitin sulfate GAG chains (typically chondroitin sulfate) and two N-linked carbohydrates. The second glycoform, referred to as 'NG' (non-glycanated) biglycan, lacks the GAG side chains. NG, but not PG biglycan recruits utrophin, an autosomal paralog of dystrophin, and an NOS-containing signaling complex to the muscle cell membrane. Recombinant NG biglycan can be systemically delivered to dystrophic mice where it upregulates utrophin at the membrane and improves muscle health and function. An optimized version of NG biglycan, 'TVN-102', is under development as a candidate therapeutic for DMD. A second matrix-embedded protein being evaluated for therapeutic potential is latent TGFβ binding protein 4 (LTBP4). Identified in a genomic screen for modifiers of muscular dystrophy, LTBP4 binds both TGFβ and myostatin. Genetic studies identified the hinge region of LTBP4 as linked to TGFβ release and contributing to the "hyper-TGFβ" signaling state that promotes fibrosis in muscular dystrophy. This hinge region can be stabilized by antibodies directed towards this domain. Stabilizing the hinge region of LTBP4 is expected to reduce latent TGFβ release and thus reduce fibrosis. Copyright © 2018 Elsevier B.V. All rights reserved.
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Kim, Hanseong; Zou, Taisong; Modi, Chintan; ...
2014-12-31
In proteins, functional divergence involves mutations that modify structure and dynamics. In this paper, we provide experimental evidence for an evolutionary mechanism driven solely by long-range dynamic motions without significant backbone adjustments, catalytic group rearrangements, or changes in subunit assembly. Crystallographic structures were determined for several reconstructed ancestral proteins belonging to a GFP class frequently employed in superresolution microscopy. Their chain flexibility was analyzed using molecular dynamics and perturbation response scanning. The green-to-red photoconvertible phenotype appears to have arisen from a common green ancestor by migration of a knob-like anchoring region away from the active site diagonally across the βmore » barrel fold. The allosterically coupled mutational sites provide active site conformational mobility via epistasis. We propose that light-induced chromophore twisting is enhanced in a reverse-protonated subpopulation, activating internal acid-base chemistry and backbone cleavage to enlarge the chromophore. Finally, dynamics-driven hinge migration may represent a more general platform for the evolution of novel enzyme activities.« less
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Silin, D; Lyubomska, O; Ludlow, M; Duprex, W P; Rima, B K
2007-12-01
We demonstrate that insertion of the open reading frame of enhanced green fluorescent protein (EGFP) into the coding sequence for the second hinge region of the viral L (large) protein (RNA-dependent RNA polymerase) attenuates a wild-type canine distemper virus. Moreover, we show that single intranasal immunization with this recombinant virus provides significant protection against challenge with the virulent parental virus. Protection against wild-type challenge was gained either after recovery of cellular immunity postimmunization or after development of neutralizing antibodies. Insertion of EGFP seems to result in overattenuation of the virus, while our previous experiments demonstrated that the insertion of an epitope tag into a similar position did not affect L protein function. Thus, a desirable level of attenuation could be reached by manipulating the length of the insert (in the second hinge region of the L protein), providing additional tools for optimization of controlled attenuation. This strategy for controlled attenuation may be useful for a "quick response" in vaccine development against well-known and "new" viral infections and could be combined efficiently with other strategies of vaccine development and delivery systems.
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Silin, D.; Lyubomska, O.; Ludlow, M.; Duprex, W. P.; Rima, B. K.
2007-01-01
We demonstrate that insertion of the open reading frame of enhanced green fluorescent protein (EGFP) into the coding sequence for the second hinge region of the viral L (large) protein (RNA-dependent RNA polymerase) attenuates a wild-type canine distemper virus. Moreover, we show that single intranasal immunization with this recombinant virus provides significant protection against challenge with the virulent parental virus. Protection against wild-type challenge was gained either after recovery of cellular immunity postimmunization or after development of neutralizing antibodies. Insertion of EGFP seems to result in overattenuation of the virus, while our previous experiments demonstrated that the insertion of an epitope tag into a similar position did not affect L protein function. Thus, a desirable level of attenuation could be reached by manipulating the length of the insert (in the second hinge region of the L protein), providing additional tools for optimization of controlled attenuation. This strategy for controlled attenuation may be useful for a “quick response” in vaccine development against well-known and “new” viral infections and could be combined efficiently with other strategies of vaccine development and delivery systems. PMID:17898047
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Huang, Yongqi; Gao, Meng; Su, Zhengding
2018-02-01
Three-dimensional (3D) domain swapping is a mechanism to form protein oligomers. It has been proposed that several factors, including proline residues in the hinge region, may affect the occurrence of 3D domain swapping. Although introducing prolines into the hinge region has been found to promote domain swapping for some proteins, the opposite effect has also been observed in several studies. So far, how proline affects 3D domain swapping remains elusive. In this work, based on a large set of 3D domain-swapped structures, we performed a systematic analysis to explore the correlation between the presence of proline in the hinge region and the occurrence of 3D domain swapping. We further analyzed the conformations of proline and pre-proline residues to investigate the roles of proline in 3D domain swapping. We found that more than 40% of the domain-swapped structures contained proline residues in the hinge region. Unexpectedly, conformational transitions of proline residues were rarely observed upon domain swapping. Our analyses showed that hinge regions containing proline residues preferred more extended conformations, which may be beneficial for the occurrence of domain swapping by facilitating opening of the exchanged segments.
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Dalvand, Hamid; Dehghan, Leila; Feizi, Awat; Hosseini, Seyed Ali; Amirsalari, Susan
2013-01-01
The purpose of this study was to examine the impacts of hinged and solid anklefoot orthoses (AFOs) on standing and walking abilities in children with spastic diplegia. In a quasi-experimental design, 30 children with spastic diplegia, aged 4-6 years were recruited. They were matched in terms of age, IQ, and level of GMFCS E&R. Children were randomly assigned into 3 groups: a hinged AFO group (n=10) plus occupational therapy (OT), a solid AFO group (n=10) plus OT, a control group who used only OT for three months. Gross motor abilities were measured using Gross Motor Measure Function (GMFM). We obtained statistically significant differences in the values between baseline and after treatment in all groups. The groups were also significantly different in total GMFM after intervention. Furthermore, there were differences between hinged AFOs and solid AFOs groups, and between hinged AFOs and control groups. We concluded that gross motor function was improved in all groups; however, hinged AFOs group appears to improve the gross motor function better than solid AFOs and control groups.
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Liu, Zhaoqun; Zhou, Zhi; Wang, Lingling; Song, Xiaorui; Chen, Hao; Wang, Weilin; Liu, Rui; Wang, Mengqiang; Wang, Hao; Song, Linsheng
2015-08-01
Enkephalinergic neuroendocrine-immune regulatory system is one of the most important neuroendocrine-immune systems in both vertebrates and invertebrates for its significant role in the immune regulation. In the present study, the early onset of enkephalinergic nervous system and its immunomodulation on the developing immune system during the ontogenesis of oyster Crassostrea gigas were investigated to illustrate the function of neural regulation on the innate immune system in oyster larvae. [Met(5)]-enkephalin (Met-ENK) was firstly observed on the marginal of the dorsal half of D-hinged larvae. Six immune-related molecules, including four PRRs (CgCTL-1, CgCTL-2, CgCTL-4, CgNatterin-3) and two immune effectors (CgTNF-1 and CgEcSOD) were detected in the early developmental stages of trochophore, D-hinged and umbo larvae of oyster. After incubated with [Met(5)]-enkephalin, the mRNA expression level of all the PRRs changed significantly (p < 0.05). In trochophore larvae, the expression level of CgNatterin-3 decreased dramatically (p < 0.05) at 6 h, and the expression level of CgCTL-4 was significantly down-regulated at 3 h and 6 h (p < 0.05), respectively. In D-hinged and umbo larvae, only CgCTL-1 was significantly down-regulated and the differences were significant at 3 h and 6 h (p < 0.05), while the expression level of CgCTL-2 and CgCTL-4 increased significantly at 3 h after treatment (p < 0.05). Moreover, the expression levels of immune effectors were up-regulated significantly at 3 h and 6 h in trochophore larvae (p < 0.05). The expression level of CgTNF-1 in both blank and experiment groups was up-regulated but there was no significant difference in D-hinged larvae stage. On the contrary, the expression level of CgEcSOD in D-hinged larvae decreased dramatically at 3 h and 6 h after [Met(5)]-enkephalin incubation (p < 0.05). In umbo larvae, the expression level of CgTNF-1 and CgEcSOD in the experiment group increased significantly at 6 h after [Met(5)]-enkephalin treatment (p < 0.05), while no significant difference was found in the blank group. In addition, the anti-bacterial activities of the total protein extract from trochophore, D-hinged and umbo larvae increased significantly (p < 0.05) at both 3 h and 6 h after [Met(5)]-enkephalin incubation compared to that in the blank group, and PO activities of both D-hinged and umbo larvae total protein extract increased significantly (p < 0.05) while no significant difference was observed in trochophore larvae. The PO activities of the total protein extract in all the experiment groups decreased after the treatment with [Met(5)]-enkephalin for 6 h, but no significant difference was observed when compared to the blank group. Furthermore, after incubation for 6 h, the concentration of both CgTNF-1 and CgIL17-5 increased dramatically compared to that in the blank group (p < 0.05). These results together indicated that the enkephalinergic nervous system of oyster was firstly appeared in D-hinged larvae, while the primitive immune defense system existed in the region of prototroch in trochophore larvae and developed maturely after D-hinged larvae. The developing immune system could be regulated by the neurotransmitter [Met(5)]-enkephalin released by the neuroendocrine system in oyster C. gigas. Copyright © 2015 Elsevier Ltd. All rights reserved.
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On the Roles of Substrate Binding and Hinge Unfolding in Conformational Changes of Adenylate Kinase
DOE Office of Scientific and Technical Information (OSTI.GOV)
Brokaw, Jason B.; Chu, Jhih-wei
2010-11-17
We characterized the conformational change of adenylate kinase (AK) between open and closed forms by conducting five all-atom molecular-dynamics simulations, each of 100 ns duration. Different initial structures and substrate binding configurations were used to probe the pathways of AK conformational change in explicit solvent, and no bias potential was applied. A complete closed-to-open and a partial open-to-closed transition were observed, demonstrating the direct impact of substrate-mediated interactions on shifting protein conformation. The sampled configurations suggest two possible pathways for connecting the open and closed structures of AK, affirming the prediction made based on available x-ray structures and earlier worksmore » of coarse-grained modeling. The trajectories of the all-atom molecular-dynamics simulations revealed the complexity of protein dynamics and the coupling between different domains during conformational change. Calculations of solvent density and density fluctuations surrounding AK did not show prominent variation during the transition between closed and open forms. Finally, we characterized the effects of local unfolding of an important hinge near Pro177 on the closed-to-open transition of AK and identified a novel mechanism by which hinge unfolding modulates protein conformational change. The local unfolding of Pro177 hinge induces alternative tertiary contacts that stabilize the closed structure and prevent the opening transition.« less
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Jones, Kevin B.; Griffin, Anthony M.; Chandrasekar, Coonoor R.; Biau, David; Babinet, Antoine; Deheshi, Benjamin; Bell, Robert S.; Grimer, Robert J.; Wunder, Jay S.; Ferguson, Peter C.
2011-01-01
Background and Objectives Functional outcomes following oncologic total femoral endoprosthetic reconstruction (TFR) are lacking. We compared patient-oriented functional results of TFRs to proximal femur and distal femur reconstructions (PFR and DFR). We also compared function and complications with regard to knee and hip componentry. Methods 54 TFR patients were identified from 3 institutional prospective databases. 41 had fixed- and 13 had rotating-hinge knees, 37 hemiarthroplasty and 17 total hip arthroplasty componentry. Toronto Extremity Salvage Scores (TESS) for n=27 were compared between groups and to cohorts of PFR (n=31) and DFR (n=85) patients using the Mann-Whitney U test. Results Follow-up averaged 4 years. Mechanical complications included 5 hip dislocations and 1 femoral malrotation. Four dislocations were in fixed-hinge implants, all in those lacking abductor reattachment. TESS averaged 69.3±17.8, statistically decreased from DFR (p=0.002) and PFR patients (p=0.036). No significant differences were detected between patients in the fixed-hinge (n=18) and rotating-hinge (n=9) groups (p = 0.944), or total hip (n=8) and hemiarthroplasty (n=19) groups (p=0.633). Conclusions TFR is reserved for extreme cases of limb salvage, portending a poor prognosis overall. Function reflects additive impairments from PFR and DFR. TFR outcomes differ little with rotating- or fixed-hinge, total hip or hemiarthroplasty implants. PMID:21695701
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Structure–kinetic relationship study of CDK8/CycC specific compounds
Schneider, Elisabeth V.; Böttcher, Jark; Huber, Robert; Maskos, Klaus; Neumann, Lars
2013-01-01
In contrast with the very well explored concept of structure–activity relationship, similar studies are missing for the dependency between binding kinetics and compound structure of a protein ligand complex, the structure–kinetic relationship. Here, we present a structure–kinetic relationship study of the cyclin-dependent kinase 8 (CDK8)/cyclin C (CycC) complex. The scaffold moiety of the compounds is anchored in the kinase deep pocket and extended with diverse functional groups toward the hinge region and the front pocket. These variations can cause the compounds to change from fast to slow binding kinetics, resulting in an improved residence time. The flip of the DFG motif (“DMG” in CDK8) to the inactive DFG-out conformation appears to have relatively little influence on the velocity of binding. Hydrogen bonding with the kinase hinge region contributes to the residence time but has less impact than hydrophobic complementarities within the kinase front pocket. PMID:23630251
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A fully redundant power hinge for LANDSAT-D appendages
NASA Technical Reports Server (NTRS)
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.
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Kingston, Anthony W; Liao, Xiaojie; Helmann, John D
2013-11-01
In Bacillus subtilis, the extracytoplasmic function (ECF) σ factors σ(M) , σ(W) and σ(X) all contribute to resistance against lantibiotics. Nisin, a model lantibiotic, has a dual mode of action: it inhibits cell wall synthesis by binding lipid II, and this complex also forms pores in the cytoplasmic membrane. These activities can be separated in a nisin hinge-region variant (N20P M21P) that binds lipid II, but no longer permeabilizes membranes. The major contribution of σ(M) to nisin resistance is expression of ltaSa, encoding a stress-activated lipoteichoic acid synthase, and σ(X) functions primarily by activation of the dlt operon controlling d-alanylation of teichoic acids. Together, σ(M) and σ(X) regulate cell envelope structure to decrease access of nisin to its lipid II target. In contrast, σ(W) is principally involved in protection against membrane permeabilization as it provides little protection against the nisin hinge region variant. σ(W) contributes to nisin resistance by regulation of a signal peptide peptidase (SppA), phage shock proteins (PspA and YvlC, a PspC homologue) and tellurite resistance related proteins (YceGHI). These defensive mechanisms are also effective against other lantibiotics such as mersacidin, gallidermin and subtilin and comprise an important subset of the intrinsic antibiotic resistome of B. subtilis. © 2013 John Wiley & Sons Ltd.
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Contributions of the σW, σM, and σX Regulons to the Lantibiotic Resistome of Bacillus subtilis
Kingston, Anthony W.; Liao, Xiaojie; Helmann, John D.
2014-01-01
Summary In Bacillus subtilis, the extracytoplasmic function (ECF) σ factors σM, σW, and σX all contribute to resistance against lantibiotics. Nisin, a model lantibiotic, has a dual mode of action: it inhibits cell wall synthesis by binding lipid II, and this complex also forms pores in the cytoplasmic membrane. These activities can be separated in a nisin hinge-region variant (N20P M21P) that binds lipid II, but no longer permeabilizes membranes. The major contribution of σM to nisin resistance is expression of ltaSa, encoding a stress-activated lipoteichoic acid synthase, and σX functions primarily by activation of the dlt operon controlling D-alanylation of teichoic acids. Together, σM and σX regulate cell envelope structure to decrease access of nisin to its lipid II target. In contrast, σW is principally involved in protection against membrane permeabilization as it provides little protection against the nisin hinge region variant. σW contributes to nisin resistance by regulation of a signal peptide peptidase (SppA), phage shock proteins (PspA and YvlC, a PspC homolog), and tellurite resistance related proteins (YceGHI). These defensive mechanisms are also effective against other lantibiotics such as mersacidin, gallidermin, and subtilin and comprise an important subset of the intrinsic antibiotic resistome of B. subtilis. PMID:23980836
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Jones, Kevin B; Griffin, Anthony M; Chandrasekar, Coonoor R; Biau, David; Babinet, Antoine; Deheshi, Benjamin; Bell, Robert S; Grimer, Robert J; Wunder, Jay S; Ferguson, Peter C
2011-11-01
Functional outcomes following oncologic total femoral endoprosthetic reconstruction (TFR) are lacking. We compared patient-oriented functional results of TFRs to proximal femur and distal femur reconstructions (PFR and DFR). We also compared function and complications with regard to knee and hip componentry. Fifty-four TFR patients were identified from three institutional prospective databases. Forty-one had fixed- and 13 had rotating-hinge knees, 37 hemiarthroplasty and 17 total hip arthroplasty componentry. Toronto Extremity Salvage Scores (TESS) for n = 27 were compared between groups and to cohorts of PFR (n = 31) and DFR (n = 85) patients using the Mann-Whitney U-test. Follow-up averaged 4 years. Mechanical complications included five hip dislocations and one femoral malrotation. Four dislocations were in fixed-hinge implants, all in those lacking abductor reattachment. TESS averaged 69.3 ± 17.8, statistically decreased from DFR (P = 0.002) and PFR patients (P = 0.036). No significant differences were detected between patients in the fixed-hinge (n = 18) and rotating-hinge (n = 9) groups (P = 0.944), or total hip (n = 8) and hemiarthroplasty (n = 19) groups (P = 0.633). TFR is reserved for extreme cases of limb salvage, portending a poor prognosis overall. Function reflects additive impairments from PFR and DFR. TFR outcomes differ little with rotating- or fixed-hinge, total hip or hemiarthroplasty implants. Copyright © 2011 Wiley Periodicals, Inc.
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Bioinformatic scaling of allosteric interactions in biomedical isozymes
NASA Astrophysics Data System (ADS)
Phillips, J. C.
2016-09-01
Allosteric (long-range) interactions can be surprisingly strong in proteins of biomedical interest. Here we use bioinformatic scaling to connect prior results on nonsteroidal anti-inflammatory drugs to promising new drugs that inhibit cancer cell metabolism. Many parallel features are apparent, which explain how even one amino acid mutation, remote from active sites, can alter medical results. The enzyme twins involved are cyclooxygenase (aspirin) and isocitrate dehydrogenase (IDH). The IDH results are accurate to 1% and are overdetermined by adjusting a single bioinformatic scaling parameter. It appears that the final stage in optimizing protein functionality may involve leveling of the hydrophobic limits of the arms of conformational hydrophilic hinges.
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Saget, B M; Shevell, D E; Walker, G C
1995-03-01
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 methylphosphotriester lesion converts Ada into a transcriptional activator of the ada and alkA genes. Activation of ada, but not alkA, requires elements contained within the carboxyl-terminal domain of Ada. In addition, physiologically relevant concentrations of the unmethylated form of Ada specifically inhibit methylated Ada-promoted ada transcription both in vitro and in vivo and it has been suggested that this phenomenon plays a pivotal role in the down-regulation of the adaptive response. A set of site-directed mutations were generated within the hinge region, changing the lysine residue at position 178 to leucine, valine, glycine, tyrosine, arginine, cysteine, proline, and serine. All eight mutant proteins have deficiencies in their ability to activate ada transcription in the presence or absence of a methylating agent but are proficient in alkA activation. AdaK178P (lysine 178 changed to proline) is completely defective for the transcriptional activation function of ada while it is completely proficient for transcriptional activation of alkA. In addition, AdaK178P possesses both classes of DNA repair activities both in vitro and in vivo. Transcriptional activation of ada does not occur if both the amino- and carboxyl-terminal domains are produced separately within the same cell. The mutation at position 178 might interfere with activation of ada transcription by changing a critical contact with RNA polymerase, by causing a conformational change of Ada, or by interfering with the communication of conformational information between the amino- and the carboxyl-terminal domains. These results indicate that the hinge region of Ada is important for ada but not alkA transcription and further support the notion that the mechanism(s) by which Ada activates ada transcription differs from that by which it activates transcription at alkA.
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Molecular mechanics of 30S subunit head rotation.
Mohan, Srividya; Donohue, John Paul; Noller, Harry F
2014-09-16
During ribosomal translocation, a process central to the elongation phase of protein synthesis, movement of mRNA and tRNAs requires large-scale rotation of the head domain of the small (30S) subunit of the ribosome. It has generally been accepted that the head rotates by pivoting around the neck helix (h28) of 16S rRNA, its sole covalent connection to the body domain. Surprisingly, we observe that the calculated axis of rotation does not coincide with the neck. Instead, comparative structure analysis across 55 ribosome structures shows that 30S head movement results from flexing at two hinge points lying within conserved elements of 16S rRNA. Hinge 1, although located within the neck, moves by straightening of the kinked helix h28 at the point of contact with the mRNA. Hinge 2 lies within a three-way helix junction that extends to the body through a second, noncovalent connection; its movement results from flexing between helices h34 and h35 in a plane orthogonal to the movement of hinge 1. Concerted movement at these two hinges accounts for the observed magnitudes of head rotation. Our findings also explain the mode of action of spectinomycin, an antibiotic that blocks translocation by binding to hinge 2.
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Molecular mechanics of 30S subunit head rotation
Mohan, Srividya; Donohue, John Paul; Noller, Harry F.
2014-01-01
During ribosomal translocation, a process central to the elongation phase of protein synthesis, movement of mRNA and tRNAs requires large-scale rotation of the head domain of the small (30S) subunit of the ribosome. It has generally been accepted that the head rotates by pivoting around the neck helix (h28) of 16S rRNA, its sole covalent connection to the body domain. Surprisingly, we observe that the calculated axis of rotation does not coincide with the neck. Instead, comparative structure analysis across 55 ribosome structures shows that 30S head movement results from flexing at two hinge points lying within conserved elements of 16S rRNA. Hinge 1, although located within the neck, moves by straightening of the kinked helix h28 at the point of contact with the mRNA. Hinge 2 lies within a three-way helix junction that extends to the body through a second, noncovalent connection; its movement results from flexing between helices h34 and h35 in a plane orthogonal to the movement of hinge 1. Concerted movement at these two hinges accounts for the observed magnitudes of head rotation. Our findings also explain the mode of action of spectinomycin, an antibiotic that blocks translocation by binding to hinge 2. PMID:25187561
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Identification of key residues for protein conformational transition using elastic network model.
Su, Ji Guo; Xu, Xian Jin; Li, Chun Hua; Chen, Wei Zu; Wang, Cun Xin
2011-11-07
Proteins usually undergo conformational transitions between structurally disparate states to fulfill their functions. The large-scale allosteric conformational transitions are believed to involve some key residues that mediate the conformational movements between different regions of the protein. In the present work, a thermodynamic method based on the elastic network model is proposed to predict the key residues involved in protein conformational transitions. In our method, the key functional sites are identified as the residues whose perturbations largely influence the free energy difference between the protein states before and after transition. Two proteins, nucleotide binding domain of the heat shock protein 70 and human/rat DNA polymerase β, are used as case studies to identify the critical residues responsible for their open-closed conformational transitions. The results show that the functionally important residues mainly locate at the following regions for these two proteins: (1) the bridging point at the interface between the subdomains that control the opening and closure of the binding cleft; (2) the hinge region between different subdomains, which mediates the cooperative motions between the corresponding subdomains; and (3) the substrate binding sites. The similarity in the positions of the key residues for these two proteins may indicate a common mechanism in their conformational transitions.
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Control-surface hinge-moment calculations for a high-aspect-ratio supercritical wing
NASA Technical Reports Server (NTRS)
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.
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Control-surface hinge-moment calculations for a high-aspect-ratio supercritical wing
DOE Office of Scientific and Technical Information (OSTI.GOV)
Perry, B.I.
1978-09-01
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 experimentalmore » 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.« less
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Allostery through protein-induced DNA bubbles
Traverso, Joseph J.; Manoranjan, Valipuram S.; Bishop, A. R.; ...
2015-03-12
Allostery through DNA is increasingly recognized as an important modulator of DNA functions. Here, we show that the coalescence of protein-induced DNA bubbles can mediate allosteric interactions that drive protein aggregation. We propose that such allostery may regulate DNA's flexibility and the assembly of the transcription machinery. Mitochondrial transcription factor A (TFAM), a dual-function protein involved in mitochondrial DNA (mtDNA) packaging and transcription initiation, is an ideal candidate to test such a hypothesis owing to its ability to locally unwind the double helix. Numerical simulations demonstrate that the coalescence of TFAM-induced bubbles can explain experimentally observed TFAM oligomerization. The resultingmore » melted DNA segment, approximately 10 base pairs long, around the joints of the oligomers act as flexible hinges, which explains the efficiency of TFAM in compacting DNA. Since mitochondrial polymerase (mitoRNAP) is involved in melting the transcription bubble, TFAM may use the same allosteric interaction to both recruit mitoRNAP and initiate transcription.« less
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Creep and cracking of concrete hinges: insight from centric and eccentric compression experiments.
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.
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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.
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Ku proteins function as corepressors to regulate farnesoid X receptor-mediated gene expression
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ohno, Masae; Kunimoto, Masaaki; Nishizuka, Makoto
2009-12-18
The farnesoid X receptor (FXR; NR1H4) is a member of the nuclear receptor superfamily and regulates the expression of genes involved in enterohepatic circulation and the metabolism of bile acids. Based on functional analyses, nuclear receptors are divided into regions A-F. To explore the cofactors interacting with FXR, we performed a pull-down assay using GST-fused to the N-terminal A/B region and the C region, which are required for the ligand-independent transactivation and DNA-binding, respectively, of FXR, and nuclear extracts from HeLa cells. We identified DNA-dependent protein kinase catalytic subunit (DNA-PKcs), Ku80, and Ku70 as FXR associated factors. These proteins aremore » known to have an important role in DNA repair, recombination, and transcription. DNA-PKcs mainly interacted with the A/B region of FXR, whereas the Ku proteins interacted with the C region and with the D region (hinge region). Chromatin immunoprecipitation assays revealed that the Ku proteins associated with FXR on the bile salt export pump (BSEP) promoter. Furthermore, we demonstrated that ectopic expression of the Ku proteins decreased the promoter activity and expression of BSEP gene mediated by FXR. These results suggest that the Ku proteins function as corepressors for FXR.« less
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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.
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Conformational diversity analysis reveals three functional mechanisms in proteins
Fornasari, María Silvina
2017-01-01
Protein motions are a key feature to understand biological function. Recently, a large-scale analysis of protein conformational diversity showed a positively skewed distribution with a peak at 0.5 Å C-alpha root-mean-square-deviation (RMSD). To understand this distribution in terms of structure-function relationships, we studied a well curated and large dataset of ~5,000 proteins with experimentally determined conformational diversity. We searched for global behaviour patterns studying how structure-based features change among the available conformer population for each protein. This procedure allowed us to describe the RMSD distribution in terms of three main protein classes sharing given properties. The largest of these protein subsets (~60%), which we call “rigid” (average RMSD = 0.83 Å), has no disordered regions, shows low conformational diversity, the largest tunnels and smaller and buried cavities. The two additional subsets contain disordered regions, but with differential sequence composition and behaviour. Partially disordered proteins have on average 67% of their conformers with disordered regions, average RMSD = 1.1 Å, the highest number of hinges and the longest disordered regions. In contrast, malleable proteins have on average only 25% of disordered conformers and average RMSD = 1.3 Å, flexible cavities affected in size by the presence of disordered regions and show the highest diversity of cognate ligands. Proteins in each set are mostly non-homologous to each other, share no given fold class, nor functional similarity but do share features derived from their conformer population. These shared features could represent conformational mechanisms related with biological functions. PMID:28192432
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The third RNA recognition motif of Drosophila ELAV protein has a role in multimerization.
Toba, Gakuta; White, Kalpana
2008-03-01
ELAV is a neuron-specific RNA-binding protein in Drosophila that is required for development and maintenance of neurons. ELAV regulates alternative splicing of Neuroglian and erect wing (ewg) transcripts, and has been shown to form a multimeric complex on the last ewg intron. The protein has three RNA recognition motifs (RRM1, 2 and 3) with a hinge region between RRM2 and 3. In this study, we used the yeast two-hybrid system to determine the multimerization domain of ELAV. Using deletion constructs, we mapped an interaction activity to a region containing most of RRM3. We found three conserved short sequences in RRM3 that were essential for the interaction, and also sufficient to give the interaction activity to RRM2 when introduced into it. In our in vivo functional assay, a mutation in one of the three sequences showed reduced activity in splicing regulation, underlining the functional importance of multimerization. However, RRM2 with the three RRM3 interaction sequences did not function as RRM3 in vivo, which suggested that multimerization is not the only function of RRM3. Our results are consistent with a model in which RRM3 serves as a bi-functional domain that interacts with both RNA and protein.
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The third RNA recognition motif of Drosophila ELAV protein has a role in multimerization
Toba, Gakuta; White, Kalpana
2008-01-01
ELAV is a neuron-specific RNA-binding protein in Drosophila that is required for development and maintenance of neurons. ELAV regulates alternative splicing of Neuroglian and erect wing (ewg) transcripts, and has been shown to form a multimeric complex on the last ewg intron. The protein has three RNA recognition motifs (RRM1, 2 and 3) with a hinge region between RRM2 and 3. In this study, we used the yeast two-hybrid system to determine the multimerization domain of ELAV. Using deletion constructs, we mapped an interaction activity to a region containing most of RRM3. We found three conserved short sequences in RRM3 that were essential for the interaction, and also sufficient to give the interaction activity to RRM2 when introduced into it. In our in vivo functional assay, a mutation in one of the three sequences showed reduced activity in splicing regulation, underlining the functional importance of multimerization. However, RRM2 with the three RRM3 interaction sequences did not function as RRM3 in vivo, which suggested that multimerization is not the only function of RRM3. Our results are consistent with a model in which RRM3 serves as a bi-functional domain that interacts with both RNA and protein. PMID:18203745
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Gabba, Matteo; Poblete, Simón; Rosenkranz, Tobias; Katranidis, Alexandros; Kempe, Daryan; Züchner, Tina; Winkler, Roland G.; Gompper, Gerhard; Fitter, Jörg
2014-01-01
Over the last few decades, a view has emerged showing that multidomain enzymes are biological machines evolved to harness stochastic kicks of solvent particles into highly directional functional motions. These intrinsic motions are structurally encoded, and Nature makes use of them to catalyze chemical reactions by means of ligand-induced conformational changes and states redistribution. Such mechanisms align reactive groups for efficient chemistry and stabilize conformers most proficient for catalysis. By combining single-molecule Förster resonance energy transfer measurements with normal mode analysis and coarse-grained mesoscopic simulations, we obtained results for a hinge-bending enzyme, namely phosphoglycerate kinase (PGK), which support and extend these ideas. From single-molecule Förster resonance energy transfer, we obtained insight into the distribution of conformational states and the dynamical properties of the domains. The simulations allowed for the characterization of interdomain motions of a compact state of PGK. The data show that PGK is intrinsically a highly dynamic system sampling a wealth of conformations on timescales ranging from nanoseconds to milliseconds and above. Functional motions encoded in the fold are performed by the PGK domains already in its ligand-free form, and substrate binding is not required to enable them. Compared to other multidomain proteins, these motions are rather fast and presumably not rate-limiting in the enzymatic reaction. Ligand binding slightly readjusts the orientation of the domains and feasibly locks the protein motions along a preferential direction. In addition, the functionally relevant compact state is stabilized by the substrates, and acts as a prestate to reach active conformations by means of Brownian motions. PMID:25418172
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Morales, Yalemi; Olsen, Keith J; Bulcher, Jacqueline M; Johnson, Sean J
2018-01-01
The FRH (frequency-interacting RNA helicase) protein is the Neurospora crassa homolog of yeast Mtr4, an essential RNA helicase that plays a central role in RNA metabolism as an activator of the nuclear RNA exosome. FRH is also a required component of the circadian clock, mediating protein interactions that result in the rhythmic repression of gene expression. Here we show that FRH unwinds RNA substrates in vitro with a kinetic profile similar to Mtr4, indicating that while FRH has acquired additional functionality, its core helicase function remains intact. In contrast with the earlier FRH structures, a new crystal form of FRH results in an ATP binding site that is undisturbed by crystal contacts and adopts a conformation consistent with nucleotide binding and hydrolysis. Strikingly, this new FRH structure adopts an arch domain conformation that is dramatically altered from previous structures. Comparison of the existing FRH structures reveals conserved hinge points that appear to facilitate arch motion. Regions in the arch have been previously shown to mediate a variety of protein-protein interactions critical for RNA surveillance and circadian clock functions. The conformational changes highlighted in the FRH structures provide a platform for investigating the relationship between arch dynamics and Mtr4/FRH function.
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Single chain Fc-dimer-human growth hormone fusion protein for improved drug delivery.
Zhou, Li; Wang, Hsuan-Yao; Tong, Shanshan; Okamoto, Curtis T; Shen, Wei-Chiang; Zaro, Jennica L
2017-02-01
Fc fusion protein technology has been successfully used to generate long-acting forms of several protein therapeutics. In this study, a novel Fc-based drug carrier, single chain Fc-dimer (sc(Fc) 2 ), was designed to contain two Fc domains recombinantly linked via a flexible linker. Since the Fc dimeric structure is maintained through the flexible linker, the hinge region was omitted to further stabilize it against proteolysis and reduce FcγR-related effector functions. The resultant sc(Fc) 2 candidate preserved the neonatal Fc receptor (FcRn) binding. sc(Fc) 2 -mediated delivery was then evaluated using a therapeutic protein with a short plasma half-life, human growth hormone (hGH), as the protein drug cargo. This novel carrier protein showed a prolonged in vivo half-life and increased hGH-mediated bioactivity compared to the traditional Fc-based drug carrier. sc(Fc) 2 technology has the potential to greatly advance and expand the use of Fc-technology for improving the pharmacokinetics and bioactivity of protein therapeutics. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Ancestral and derived protein import pathways in the mitochondrion of Reclinomonas americana.
Tong, Janette; Dolezal, Pavel; Selkrig, Joel; Crawford, Simon; Simpson, Alastair G B; Noinaj, Nicholas; Buchanan, Susan K; Gabriel, Kipros; Lithgow, Trevor
2011-05-01
The evolution of mitochondria from ancestral bacteria required that new protein transport machinery be established. Recent controversy over the evolution of these new molecular machines hinges on the degree to which ancestral bacterial transporters contributed during the establishment of the new protein import pathway. Reclinomonas americana is a unicellular eukaryote with the most gene-rich mitochondrial genome known, and the large collection of membrane proteins encoded on the mitochondrial genome of R. americana includes a bacterial-type SecY protein transporter. Analysis of expressed sequence tags shows R. americana also has components of a mitochondrial protein translocase or "translocase in the inner mitochondrial membrane complex." Along with several other membrane proteins encoded on the mitochondrial genome Cox11, an assembly factor for cytochrome c oxidase retains sequence features suggesting that it is assembled by the SecY complex in R. americana. Despite this, protein import studies show that the RaCox11 protein is suited for import into mitochondria and functional complementation if the gene is transferred into the nucleus of yeast. Reclinomonas americana provides direct evidence that bacterial protein transport pathways were retained, alongside the evolving mitochondrial protein import machinery, shedding new light on the process of mitochondrial evolution.
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Synthesis and characterization of recombinant abductin-based proteins.
Su, Renay S-C; Renner, Julie N; Liu, Julie C
2013-12-09
Recombinant proteins are promising tools for tissue engineering and drug delivery applications. Protein-based biomaterials have several advantages over natural and synthetic polymers, including precise control over amino acid composition and molecular weight, modular swapping of functional domains, and tunable mechanical and physical properties. In this work, we describe recombinant proteins based on abductin, an elastomeric protein that is found in the inner hinge of bivalves and functions as a coil spring to keep shells open. We illustrate, for the first time, the design, cloning, expression, and purification of a recombinant protein based on consensus abductin sequences derived from Argopecten irradians . The molecular weight of the protein was confirmed by mass spectrometry, and the protein was 94% pure. Circular dichroism studies showed that the dominant structures of abductin-based proteins were polyproline II helix structures in aqueous solution and type II β-turns in trifluoroethanol. Dynamic light scattering studies illustrated that the abductin-based proteins exhibit reversible upper critical solution temperature behavior and irreversible aggregation behavior at high temperatures. A LIVE/DEAD assay revealed that human umbilical vein endothelial cells had a viability of 98 ± 4% after being cultured for two days on the abductin-based protein. Initial cell spreading on the abductin-based protein was similar to that on bovine serum albumin. These studies thus demonstrate the potential of abductin-based proteins in tissue engineering and drug delivery applications due to the cytocompatibility and its response to temperature.
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Optocontrol of glutamate receptor activity by single side-chain photoisomerization
Klippenstein, Viktoria; Hoppmann, Christian; Ye, Shixin; Wang, Lei; Paoletti, Pierre
2017-01-01
Engineering light-sensitivity into proteins has wide ranging applications in molecular studies and neuroscience. Commonly used tethered photoswitchable ligands, however, require solvent-accessible protein labeling, face structural constrains, and are bulky. Here, we designed a set of optocontrollable NMDA receptors by directly incorporating single photoswitchable amino acids (PSAAs) providing genetic encodability, reversibility, and site tolerance. We identified several positions within the multi-domain receptor endowing robust photomodulation. PSAA photoisomerization at the GluN1 clamshell hinge is sufficient to control glycine sensitivity and activation efficacy. Strikingly, in the pore domain, flipping of a M3 residue within a conserved transmembrane cavity impacts both gating and permeation properties. Our study demonstrates the first detection of molecular rearrangements in real-time due to the reversible light-switching of single amino acid side-chains, adding a dynamic dimension to protein site-directed mutagenesis. This novel approach to interrogate neuronal protein function has general applicability in the fast expanding field of optopharmacology. DOI: http://dx.doi.org/10.7554/eLife.25808.001 PMID:28534738
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Mou, Yun; Huang, Po-Ssu; Thomas, Leonard M; Mayo, Stephen L
2015-08-14
In standard implementations of computational protein design, a positive-design approach is used to predict sequences that will be stable on a given backbone structure. Possible competing states are typically not considered, primarily because appropriate structural models are not available. One potential competing state, the domain-swapped dimer, is especially compelling because it is often nearly identical with its monomeric counterpart, differing by just a few mutations in a hinge region. Molecular dynamics (MD) simulations provide a computational method to sample different conformational states of a structure. Here, we tested whether MD simulations could be used as a post-design screening tool to identify sequence mutations leading to domain-swapped dimers. We hypothesized that a successful computationally designed sequence would have backbone structure and dynamics characteristics similar to that of the input structure and that, in contrast, domain-swapped dimers would exhibit increased backbone flexibility and/or altered structure in the hinge-loop region to accommodate the large conformational change required for domain swapping. While attempting to engineer a homodimer from a 51-amino-acid fragment of the monomeric protein engrailed homeodomain (ENH), we had instead generated a domain-swapped dimer (ENH_DsD). MD simulations on these proteins showed increased B-factors derived from MD simulation in the hinge loop of the ENH_DsD domain-swapped dimer relative to monomeric ENH. Two point mutants of ENH_DsD designed to recover the monomeric fold were then tested with an MD simulation protocol. The MD simulations suggested that one of these mutants would adopt the target monomeric structure, which was subsequently confirmed by X-ray crystallography. Copyright © 2015. Published by Elsevier Ltd.
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A non-foaming proteosurfactant engineered from Ranaspumin-2.
Frey, Shelli L; Todd, Jacob; Wurtzler, Elizabeth; Strelez, Carly R; Wendell, David
2015-09-01
Advances in biological surfactant proteins have already yielded a diverse range of benefits from dramatically improved survival rates for premature births to artificial photosynthesis. Presented here is the design, development, and analysis of a novel biosurfactant protein we call Surfactant Resisting Foam formatioN (SRFN). Starting with the Tungara frog's foam forming protein Ranaspumin-2, we have engineered a new surfactant protein with a destabilized hinge region to alter the kinetics and equilibrium of the protein structural transition from aqueous globular form to an extended surfactant structure at the air/water interface. SRFN is capable of approximately the same total surface tension reduction, but with the unique property of forming quickly collapsible foams. The difference in foam formation is attributed to the destabilizing glycine substitutions engineered into the hinge region. Surfactants used specifically to increase wettability, such as those used in agricultural applications would benefit from this new proteosurfactant since foamed liquid has greater wind resistance and decreased dispersal. Indeed, given growing concern of organsilicone surfactant effects on declining bee populations, biological surfactant proteins have several unique advantages over more common amphiphiles in that they can be renewably sourced, are environmentally friendly, degrade readily into non-toxic byproducts, and reduce surface tension without deleterious effects on cell membranes. Copyright © 2015 Elsevier B.V. All rights reserved.
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Desclozeaux, Marion; Krylova, Irina N.; Horn, Florence; Fletterick, Robert J.; Ingraham, Holly A.
2002-01-01
Steroidogenic factor 1 (SF-1) is an orphan nuclear receptor with no known ligand. We showed previously that phosphorylation at serine 203 located N′-terminal to the ligand binding domain (LBD) enhanced cofactor recruitment, analogous to the ligand-mediated recruitment in ligand-dependent receptors. In this study, results of biochemical analyses and an LBD helix assembly assay suggest that the SF-1 LBD adopts an active conformation, with helices 1 and 12 packed against the predicted alpha-helical bundle, in the apparent absence of ligand. Fine mapping of the previously defined proximal activation function in SF-1 showed that the activation function mapped fully to helix 1 of the LBD. Limited proteolyses demonstrate that phosphorylation of S203 in the hinge region mimics the stabilizing effects of ligand on the LBD. Moreover, similar effects were observed in an SF-1/thyroid hormone LBD chimera receptor, illustrating that the S203 phosphorylation effects are transferable to a heterologous ligand-dependent receptor. Our collective data suggest that the hinge together with helix 1 is an individualized specific motif, which is tightly associated with its cognate LBD. For SF-1, we find that this intramolecular association and hence receptor activity are further enhanced by mitogen-activated protein kinase phosphorylation, thus mimicking many of the ligand-induced changes observed for ligand-dependent receptors. PMID:12242296
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Aerodynamic analysis of seamless horizontal stabilizer
NASA Astrophysics Data System (ADS)
Nithya, S.; Kanimozhi, S.
2017-05-01
This project presents an investigative view into the concept of seamless aeroelastic wing and hingeless flexible trailing edge. Wings are designed to provide maximum lift and minimal drag and weight. But with conventional wings where rivets are used and the control surfaces are separately hinged, parasite drag comes into play. This project is about analysing a smooth seamless wing with hinge-less flexible trailing edge. This type of wing reduces the drag considerably and the hinge-less trailing edge leads to a minimal control demand and reduces the noise produced when the aircraft comes for landing. Seamless aeroelastic wing will function as an integrated one piece lifting and control surface. It has been designed to enhance a desirable wing camber for control by deflecting a hinge-less flexible trailing edge part instead of a traditional hinged control surface. This kind of flexible wing can be achieved either by a curved beam and disc actuation mechanism or by piezo-electric materials, whose shape change can be achieved by electricity. The intent of this project is to analyze the effects of introducing the concept of Seamless Wing to the horizontal stabilizer. While the removal of rivets and serrations that hinge the elevators to the stabilizer reduces the overall drag by a reasonable value, the overall concept of a control surface-less stabilizer where the maneuvers are done by deflecting the trailing edge offers better maneuverability.
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Modi, Tushar; Huihui, Jonathan; Ghosh, Kingshuk; Ozkan, S Banu
2018-06-19
Thioredoxins (THRXs)-small globular proteins that reduce other proteins-are ubiquitous in all forms of life, from Archaea to mammals. Although ancestral thioredoxins share sequential and structural similarity with the modern-day (extant) homologues, they exhibit significantly different functional activity and stability. We investigate this puzzle by comparative studies of their (ancient and modern-day THRXs') native state ensemble, as quantified by the dynamic flexibility index (DFI), a metric for the relative resilience of an amino acid to perturbations in the rest of the protein. Clustering proteins using DFI profiles strongly resemble an alternative classification scheme based on their activity and stability. The DFI profiles of the extant proteins are substantially different around the α3, α4 helices and catalytic regions. Likewise, allosteric coupling of the active site with the rest of the protein is different between ancient and extant THRXs, possibly explaining the decreased catalytic activity at low pH with evolution. At a global level, we note that the population of low-flexibility (called hinges) and high-flexibility sites increases with evolution. The heterogeneity (quantified by the variance) in DFI distribution increases with the decrease in the melting temperature typically associated with the evolution of ancient proteins to their modern-day counterparts.This article is part of a discussion meeting issue 'Allostery and molecular machines'. © 2018 The Author(s).
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Galván Duque-Gastélum, Carlos; Quiñones-Uriostegui, Ivett; Mendoza, Felipe; Rodríguez, Gerardo
2014-07-01
Ortheses are devices that assist in the function of the limbs, contributing with stability and support to the involved joints. KAFOs (knee-ankle-foot orthosis) are mainly indicated for people with muscular or neural diseases that affect the lower limbs. The actual designs of knee hinges for KAFOs compromise the stability and mobility of the limb. In this work, it was tested the feasibility of a design for a knee hinge for KAFO that should be able to modify its mechanical resistance depending on the gait phase. Orthotics biomechanical criteria and gait biomechanical requirements were considered. It was proposed an electromagnetic system in order to modify the hinge damping. In the future, the system will be interacting with a magnetorheological fluid (MR) which can change its rheological properties when a magnetic field is applied, thus, reaching different damping constants with the designed hinge. The diameter of the internal pipes required for the MR fluid to freely circulate within the orthosis was established. It was observed that the original design of the proposed orthotic hinge is feasible; however, some proposals are presented in order to achieve a better performance of the orthosis.
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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.
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Mandal, Soumit Sankar; Buchsteiner, Maximilian; Dima, Ruxandra I.; Rief, Matthias; Žoldák, Gabriel
2017-01-01
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. PMID:28533394
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Wang, Yong; Tang, Chun; Wang, Erkang; Wang, Jin
2012-01-01
An increasing number of biological machines have been revealed to have more than two macroscopic states. Quantifying the underlying multiple-basin functional landscape is essential for understanding their functions. However, the present models seem to be insufficient to describe such multiple-state systems. To meet this challenge, we have developed a coarse grained triple-basin structure-based model with implicit ligand. Based on our model, the constructed functional landscape is sufficiently sampled by the brute-force molecular dynamics simulation. We explored maltose-binding protein (MBP) which undergoes large-scale domain motion between open, apo-closed (partially closed) and holo-closed (fully closed) states responding to ligand binding. We revealed an underlying mechanism whereby major induced fit and minor population shift pathways co-exist by quantitative flux analysis. We found that the hinge regions play an important role in the functional dynamics as well as that increases in its flexibility promote population shifts. This finding provides a theoretical explanation of the mechanistic discrepancies in PBP protein family. We also found a functional “backtracking” behavior that favors conformational change. We further explored the underlying folding landscape in response to ligand binding. Consistent with earlier experimental findings, the presence of ligand increases the cooperativity and stability of MBP. This work provides the first study to explore the folding dynamics and functional dynamics under the same theoretical framework using our triple-basin functional model. PMID:22532792
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Multiscale weighted colored graphs for protein flexibility and rigidity analysis
NASA Astrophysics Data System (ADS)
Bramer, David; Wei, Guo-Wei
2018-02-01
Protein structural fluctuation, measured by Debye-Waller factors or B-factors, is known to correlate to protein flexibility and function. A variety of methods has been developed for protein Debye-Waller factor prediction and related applications to domain separation, docking pose ranking, entropy calculation, hinge detection, stability analysis, etc. Nevertheless, none of the current methodologies are able to deliver an accuracy of 0.7 in terms of the Pearson correlation coefficients averaged over a large set of proteins. In this work, we introduce a paradigm-shifting geometric graph model, multiscale weighted colored graph (MWCG), to provide a new generation of computational algorithms to significantly change the current status of protein structural fluctuation analysis. Our MWCG model divides a protein graph into multiple subgraphs based on interaction types between graph nodes and represents the protein rigidity by generalized centralities of subgraphs. MWCGs not only predict the B-factors of protein residues but also accurately analyze the flexibility of all atoms in a protein. The MWCG model is validated over a number of protein test sets and compared with many standard methods. An extensive numerical study indicates that the proposed MWCG offers an accuracy of over 0.8 and thus provides perhaps the first reliable method for estimating protein flexibility and B-factors. It also simultaneously predicts all-atom flexibility in a molecule.
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Purohit, Prasad
2011-01-01
The extent to which agonists activate synaptic receptor-channels depends on both the intrinsic tendency of the unliganded receptor to open and the amount of agonist binding energy realized in the channel-opening process. We examined mutations of the nicotinic acetylcholine receptor transmitter binding site (α subunit loop B) with regard to both of these parameters. αGly147 is an “activation” hinge where backbone flexibility maintains high values for intrinsic gating, the affinity of the resting conformation for agonists and net ligand binding energy. αGly153 is a “deactivation” hinge that maintains low values for these parameters. αTrp149 (between these two glycines) serves mainly to provide ligand binding energy for gating. We propose that a concerted motion of the two glycine hinges (plus other structural elements at the binding site) positions αTrp149 so that it provides physiologically optimal binding and gating function at the nerve-muscle synapse. PMID:21115636
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Evading pre-existing anti-hinge antibody binding by hinge engineering
Kim, Hok Seon; Kim, Ingrid; Zheng, Linda; Vernes, Jean-Michel; Meng, Y. Gloria; Spiess, Christoph
2016-01-01
ABSTRACT Antigen-binding fragments (Fab) and F(ab′)2 antibodies serve as alternative formats to full-length anti-bodies in therapeutic and immune assays. They provide the advantage of small size, short serum half-life, and lack of effector function. Several proteases associated with invasive diseases are known to cleave antibodies in the hinge-region, and this results in anti-hinge antibodies (AHA) toward the neoepitopes. The AHA can act as surrogate Fc and reintroduce the properties of the Fc that are otherwise lacking in antibody fragments. While this response is desired during the natural process of fighting disease, it is commonly unwanted for therapeutic antibody fragments. In our study, we identify a truncation in the lower hinge region of the antibody that maintains efficient proteolytic cleavage by IdeS protease. The resulting neoepitope at the F(ab′)2 C-terminus does not have detectable binding of pre-existing AHA, providing a practical route to produce F(ab′)2 in vitro by proteolytic digestion when the binding of pre-existing AHA is undesired. We extend our studies to the upper hinge region of the antibody and provide a detailed analysis of the contribution of C-terminal residues of the upper hinge of human IgG1, IgG2 and IgG4 to pre-existing AHA reactivity in human serum. While no pre-existing antibodies are observed toward the Fab of IgG2 and IgG4 isotype, a significant response is observed toward most residues of the upper hinge of human IgG1. We identify a T225L variant and the natural C-terminal D221 as solutions with minimal serum reactivity. Our work now enables the production of Fab and F(ab′)2 for therapeutic and diagnostic immune assays that have minimal reactivity toward pre-existing AHA. PMID:27606571
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Boer, D. Roeland; Ruiz-Masó, José Angel; Rueda, Manuel; Petoukhov, Maxim V.; Machón, Cristina; Svergun, Dmitri I.; Orozco, Modesto; del Solar, Gloria; Coll, Miquel
2016-01-01
DNA replication initiation is a vital and tightly regulated step in all replicons and requires an initiator factor that specifically recognizes the DNA replication origin and starts replication. RepB from the promiscuous streptococcal plasmid pMV158 is a hexameric ring protein evolutionary related to viral initiators. Here we explore the conformational plasticity of the RepB hexamer by i) SAXS, ii) sedimentation experiments, iii) molecular simulations and iv) X-ray crystallography. Combining these techniques, we derive an estimate of the conformational ensemble in solution showing that the C-terminal oligomerisation domains of the protein form a rigid cylindrical scaffold to which the N-terminal DNA-binding/catalytic domains are attached as highly flexible appendages, featuring multiple orientations. In addition, we show that the hinge region connecting both domains plays a pivotal role in the observed plasticity. Sequence comparisons and a literature survey show that this hinge region could exists in other initiators, suggesting that it is a common, crucial structural element for DNA binding and manipulation. PMID:26875695
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Gellért, Akos; Balázs, Ervin
2010-02-26
The three-dimensional structures of two cucumovirus coat proteins (CP), namely Cucumber mosaic virus (CMV) and Tomato aspermy virus (TAV), were explored by molecular dynamics (MD) simulations. The N-terminal domain and the C-terminal tail of the CPs proved to be intrinsically unstructured protein regions in aqueous solution. The N-terminal alpha-helix had a partially unrolled conformation. The thermal factor analysis of the CP loop regions demonstrated that the CMV CP had more flexible loop regions than the TAV CP. The principal component analysis (PCA) of the MD trajectories showed that the first three eigenvectors represented the three main conformational motions in the CPs. The first motion components with the highest variance contribution described an opening movement between the hinge and the N-terminal domain of both CPs. The second eigenvector showed a closing motion, while the third eigenvector represented crosswise conformational fluctuations. These new findings, together with previous results, suggest that the hinge region of CPs plays a central role in the recognition and binding of viral RNA. Copyright 2009 Elsevier Inc. All rights reserved.
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Arthrometric Evaluation of Stabilizing Effect of Knee Functional Bracing at Different Flexion Angles
Seyed Mohseni, Saeedeh; Moss, Farzam; Karimi, Hossein; Kamali, Mohammad
2009-01-01
Previous in-vivo investigations on the stabilizing efficacy of knee bracing for ACL reconstructed patients have been often limited to 20-30 degrees of knee flexion. In this study, the effectiveness of a uniaxial hinged functional brace to improve the knee stability was assessed at 30, 60 and 90 degrees of knee flexion. Arthrometry tests were conducted on 15 healthy subjects before and following wearing the brace and the tibial displacements were measured at up to 150 N anterior forces. Results indicated that functional bracing has a significant stabilizing effect throughout the range of knee flexion examined (p < 0.05). The rate of effectiveness, however, was not consistent across the flexion range, e.g., 50% at 30 degrees and only 4% at 90 degrees. It was suggested that accurate sizing and fitting as well as attention to correct hinge placement relative to the femoral condyles can limit brace migration and improve its effectiveness in mid and deep knee flexion. With using adaptive limb fittings, through flexible pads, and a polycentric joint a more significant improvement of the overall brace performance and efficacy might be obtained. Key points Functional bracing improves the knee joint stability mostly in extension posture. Unlike the non-braced condition, the least knee joint stability appears in mid and deep flexion angles when using a hinged brace. Accurate sizing and fitting and attention to correct hinge placement relative to the femoral condyles can limit brace migration and improve its effectiveness in mid and deep knee flexion. The overall brace performance and efficacy might be improved significantly using adaptive limb fittings through flexible pads and/or polycentric joints. PMID:24149533
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Smaldone, Giovanni; Vigorita, Marilisa; Ruggiero, Alessia; Balasco, Nicole; Dattelbaum, Jonathan D; D'Auria, Sabato; Del Vecchio, Pompea; Graziano, Giuseppe; Vitagliano, Luigi
2016-07-01
The Arginine Binding Protein isolated from Thermotoga maritima (TmArgBP) is a protein endowed with several peculiar properties. We have previously shown that TmArgBP dimerization is a consequence of the swapping of the C-terminal helix. Here we explored the structural determinants of TmArgBP domain swapping and oligomerization. In particular, we report a mutational analysis of the residue Pro235, which is located in the hinge region of the swapping dimer. This residue was either replaced with a Gly-Lys dipeptide (TmArgBP(P235GK)) or a Gly residue (TmArgBP(P235G)). Different forms of these mutants were generated and extensively characterized using biophysical techniques. For both TmArgBP(P235GK) and TmArgBP(P235G) mutants, the occurrence of multiple oligomerization states (monomers, dimers and trimers) was detected. The formation of well-folded monomeric forms for these mutants indicates that the dimerization through C-terminal domain swapping observed in wild-type TmArgBP is driven by conformational restraints imposed by the presence of Pro235 in the hinge region. Molecular dynamics studies corroborate this observation by showing that Gly235 assumes conformational states forbidden for Pro residues in the TmArgBP(P235G) monomer. Unexpectedly, the trimeric forms present: (a) peculiar circular dichroism spectra, (b) a great susceptibility to heating, and (c) the ability to bind the Thioflavin T dye. The present findings clearly demonstrate that single-point mutations have an important impact on the TmArgBP oligomerization process. In a wider context, they also indicate that proteins endowed with an intrinsic propensity to swap have an easy access to states with altered structural and, possibly, functional properties. Copyright © 2016. Published by Elsevier B.V.
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Smolin, N; Biehl, R; Kneller, G R; Richter, D; Smith, J C
2012-03-07
Protein function often requires large-scale domain motion. An exciting new development in the experimental characterization of domain motions in proteins is the application of neutron spin-echo spectroscopy (NSE). NSE directly probes coherent (i.e., pair correlated) scattering on the ~1-100 ns timescale. Here, we report on all-atom molecular-dynamics (MD) simulation of a protein, phosphoglycerate kinase, from which we calculate small-angle neutron scattering (SANS) and NSE scattering properties. The simulation-derived and experimental-solution SANS results are in excellent agreement. The contributions of translational and rotational whole-molecule diffusion to the simulation-derived NSE and potential problems in their estimation are examined. Principal component analysis identifies types of domain motion that dominate the internal motion's contribution to the NSE signal, with the largest being classic hinge bending. The associated free-energy profiles are quasiharmonic and the frictional properties correspond to highly overdamped motion. The amplitudes of the motions derived by MD are smaller than those derived from the experimental analysis, and possible reasons for this difference are discussed. The MD results confirm that a significant component of the NSE arises from internal dynamics. They also demonstrate that the combination of NSE with MD is potentially useful for determining the forms, potentials of mean force, and time dependence of functional domain motions in proteins. Copyright © 2012 Biophysical Society. Published by Elsevier Inc. All rights reserved.
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Smolin, N.; Biehl, R.; Kneller, G.R.; Richter, D.; Smith, J.C.
2012-01-01
Protein function often requires large-scale domain motion. An exciting new development in the experimental characterization of domain motions in proteins is the application of neutron spin-echo spectroscopy (NSE). NSE directly probes coherent (i.e., pair correlated) scattering on the ∼1–100 ns timescale. Here, we report on all-atom molecular-dynamics (MD) simulation of a protein, phosphoglycerate kinase, from which we calculate small-angle neutron scattering (SANS) and NSE scattering properties. The simulation-derived and experimental-solution SANS results are in excellent agreement. The contributions of translational and rotational whole-molecule diffusion to the simulation-derived NSE and potential problems in their estimation are examined. Principal component analysis identifies types of domain motion that dominate the internal motion's contribution to the NSE signal, with the largest being classic hinge bending. The associated free-energy profiles are quasiharmonic and the frictional properties correspond to highly overdamped motion. The amplitudes of the motions derived by MD are smaller than those derived from the experimental analysis, and possible reasons for this difference are discussed. The MD results confirm that a significant component of the NSE arises from internal dynamics. They also demonstrate that the combination of NSE with MD is potentially useful for determining the forms, potentials of mean force, and time dependence of functional domain motions in proteins. PMID:22404933
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Visualizing Key Hinges and a Potential Major Source of Compliance in the Lever Arm of Myosin
DOE Office of Scientific and Technical Information (OSTI.GOV)
J Brown; V Senthil Kumar; E ONeall-Hennessey
2011-12-31
We have determined the 2.3-{angstrom}-resolution crystal structure of a myosin light chain domain, corresponding to one type found in sea scallop catch ('smooth') muscle. This structure reveals hinges that may function in the 'on' and 'off' states of myosin. The molecule adopts two different conformations about the heavy chain 'hook' and regulatory light chain (RLC) helix D. This conformational change results in extended and compressed forms of the lever arm whose lengths differ by 10 {angstrom}. The heavy chain hook and RLC helix D hinges could thus serve as a potential major and localized source of cross-bridge compliance during themore » contractile cycle. In addition, in one of the molecules of the crystal, part of the RLC N-terminal extension is seen in atomic detail and forms a one-turn alpha-helix that interacts with RLC helix D. This extension, whose sequence is highly variable in different myosins, may thus modulate the flexibility of the lever arm. Moreover, the relative proximity of the phosphorylation site to the helix D hinge suggests a potential role for conformational changes about this hinge in the transition between the on and off states of regulated myosins.« less
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Visualizing key hinges and a potential major source of compliance in the lever arm of myosin
DOE Office of Scientific and Technical Information (OSTI.GOV)
Brown, J.H.; Robinson, H.; Senthil Kumar, V. S.
2011-01-04
We have determined the 2.3-{angstrom}-resolution crystal structure of a myosin light chain domain, corresponding to one type found in sea scallop catch ('smooth') muscle. This structure reveals hinges that may function in the 'on' and 'off' states of myosin. The molecule adopts two different conformations about the heavy chain 'hook' and regulatory light chain (RLC) helix D. This conformational change results in extended and compressed forms of the lever arm whose lengths differ by 10 {angstrom}. The heavy chain hook and RLC helix D hinges could thus serve as a potential major and localized source of cross-bridge compliance during themore » contractile cycle. In addition, in one of the molecules of the crystal, part of the RLC N-terminal extension is seen in atomic detail and forms a one-turn alpha-helix that interacts with RLC helix D. This extension, whose sequence is highly variable in different myosins, may thus modulate the flexibility of the lever arm. Moreover, the relative proximity of the phosphorylation site to the helix D hinge suggests a potential role for conformational changes about this hinge in the transition between the on and off states of regulated myosins.« less
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How insect flight steering muscles work.
Hedenström, Anders
2014-03-01
Insights into how exactly a fly powers and controls flight have been hindered by the need to unpick the dynamic complexity of the muscles involved. The wingbeats of insects are driven by two antagonistic groups of power muscles and the force is funneled to the wing via a very complex hinge mechanism. The hinge consists of several hardened and articulated cuticle elements called sclerites. This articulation is controlled by a great number of small steering muscles, whose function has been studied by means of kinematics and muscle activity. The details and partly novel function of some of these steering muscles and their tendons have now been revealed in research published in this issue of PLOS Biology. The new study from Graham Taylor and colleagues applies time-resolved X-ray microtomography to obtain a three-dimensional view of the blowfly wingbeat. Asymmetric power output is achieved by differential wingbeat amplitude on the left and right wing, which is mediated by muscular control of the hinge elements to mechanically block the wing stroke and by absorption of work by steering muscles on one of the sides. This new approach permits visualization of the motion of the thorax, wing muscles, and the hinge mechanism. This very promising line of work will help to reveal the complete picture of the flight motor of a fly. It also holds great potential for novel bio-inspired designs of fly-like micro air vehicles.
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Novel Evasion Mechanisms of the Classical Complement Pathway
Garcia, Brandon L.; Zwarthoff, Seline A.; Rooijakkers, Suzan H. M.; Geisbrecht, Brian V.
2016-01-01
Complement is a network of soluble and cell surface-associated proteins which gives rise to a self-amplifying, yet tightly regulated system with fundamental roles in immune surveillance and clearance. Complement becomes activated on the surface of ‘non-self’ cells by one of three initiating mechanisms known as the classical, lectin, or alternative pathways. Evasion of complement function is a hallmark of invasive pathogens and hematophagous organisms. While many complement inhibition strategies hinge on hijacking activities of endogenous complement regulatory proteins, an increasing number of uniquely evolved evasion molecules have been discovered over the past decade. In this review we focus on several recent investigations which have revealed mechanistically distinct inhibitors of the classical pathway. Because the classical pathway is an important and specific mediator of various autoimmune and inflammatory disorders, in-depth knowledge of novel evasion mechanisms could direct future development of therapeutic anti-inflammatory molecules. PMID:27591336
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Novel Evasion Mechanisms of the Classical Complement Pathway.
Garcia, Brandon L; Zwarthoff, Seline A; Rooijakkers, Suzan H M; Geisbrecht, Brian V
2016-09-15
Complement is a network of soluble and cell surface-associated proteins that gives rise to a self-amplifying, yet tightly regulated system with fundamental roles in immune surveillance and clearance. Complement becomes activated on the surface of nonself cells by one of three initiating mechanisms known as the classical, lectin, and alternative pathways. Evasion of complement function is a hallmark of invasive pathogens and hematophagous organisms. Although many complement-inhibition strategies hinge on hijacking activities of endogenous complement regulatory proteins, an increasing number of uniquely evolved evasion molecules have been discovered over the past decade. In this review, we focus on several recent investigations that revealed mechanistically distinct inhibitors of the classical pathway. Because the classical pathway is an important and specific mediator of various autoimmune and inflammatory disorders, in-depth knowledge of novel evasion mechanisms could direct future development of therapeutic anti-inflammatory molecules. Copyright © 2016 by The American Association of Immunologists, Inc.
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Functional buckling behavior of silicone rubber shells for biomedical use.
van der Houwen, E B; Kuiper, L H; Burgerhof, J G M; van der Laan, B F A M; Verkerke, G J
2013-12-01
The use of soft elastic biomaterials in medical devices enables substantial function integration. The consequent increased simplification in design can improve reliability at a lower cost in comparison to traditional (hard) biomaterials. Functional bi-stable buckling is one of the many new mechanisms made possible by soft materials. The buckling behavior of shells, however, is typically described from a structural failure point of view: the collapse of arches or rupture of steam vessels, for example. There is little or no literature about the functional elastic buckling of small-sized silicone rubber shells, and it is unknown whether or not theory can predict their behavior. Is functional buckling possible within the scale, material and pressure normally associated with physiological applications? An automatic speech valve is used as an example application. Silicone rubber spherical shells (diameter 30mm) with hinged and double-hinged boundaries were subjected to air pressure loading. Twelve different geometrical configurations were tested for buckling and reverse buckling pressures. Data were compared with the theory. Buckling pressure increases linearly with shell thickness and shell height. Reverse buckling shows these same relations, with pressures always below normal buckling pressure. Secondary hinges change normal/reverse buckling pressure ratios and promote symmetrical buckling. All tested configurations buckled within or closely around physiological pressures. Functional bi-stable buckling of silicone rubber shells is possible with adjustable properties in the physiological pressure range. Results can be predicted using the proposed relations and equations. Copyright © 2013 Elsevier Ltd. All rights reserved.
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Human heavy chain disease protein WIS: implications for the organization of immunoglobulin genes.
Franklin, E C; Prelli, F; Frangione, B
1979-01-01
Protein WIS is a human gamma3 heavy (H) chain disease immunoglobulin variant whose amino acid sequence is most readily interpreted by postulating that three residues of the amino terminus are followed by a deletion of most of the variable (VH) domain, which ends at the variable-constant (VC) joining region. Then there is a stretch of eight residues, three of which are unusual, while the other five have striking homology to the VC junction sequence. This is followed by a second deletion, which ends at the beginning of the quadruplicated hinge region. These findings are consistent with mutations resulting in deletions of most of the gene coding for the V region and CH1 domain followed by splicing at the VC joining region and at the hinge. These structural features fit well the notion of genetic discontinuity between V and C genes and also suggest similar mechanisms of excision and splicing in the interdomain regions of the C gene of the heavy chain. PMID:106391
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Basic N-terminus of yeast Nhp6A regulates the mechanism of its DNA flexibility enhancement.
Zhang, Jingyun; McCauley, Micah J; Maher, L James; Williams, Mark C; Israeloff, Nathan E
2012-02-10
HMGB (high-mobility group box) proteins are members of a class of small proteins that are ubiquitous in eukaryotic cells and nonspecifically bind to DNA, inducing large-angle DNA bends, enhancing the flexibility of DNA, and likely facilitating numerous important biological interactions. To determine the nature of this behavior for different HMGB proteins, we used atomic force microscopy to quantitatively characterize the bend angle distributions of DNA complexes with human HMGB2(Box A), yeast Nhp6A, and two chimeric mutants of these proteins. While all of the HMGB proteins bend DNA to preferred angles, Nhp6A promoted the formation of higher-order oligomer structures and induced a significantly broader distribution of angles, suggesting that the mechanism of Nhp6A is like a flexible hinge more than that of HMGB2(Box A). To determine the structural origins of this behavior, we used portions of the cationic N-terminus of Nhp6A to replace corresponding HMGB2(Box A) sequences. We found that the oligomerization and broader angle distribution correlated directly with the length of the N-terminus incorporated into the HMGB2(Box A) construct. Therefore, the basic N-terminus of Nhp6A is responsible for its ability to act as a flexible hinge and to form high-order structures. Copyright © 2011 Elsevier Ltd. All rights reserved.
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New tools for “hot-wiring” clathrin-mediated endocytosis with temporal and spatial precision
2017-01-01
Clathrin-mediated endocytosis (CME) is the major route of receptor internalization at the plasma membrane. Analysis of constitutive CME is difficult because the initiation of endocytic events is unpredictable. When and where a clathrin-coated pit will form and what cargo it will contain are difficult to foresee. Here we describe a series of genetically encoded reporters that allow the initiation of CME on demand. A clathrin-binding protein fragment (“hook”) is inducibly attached to an “anchor” protein at the plasma membrane, which triggers the formation of new clathrin-coated vesicles. Our design incorporates temporal and spatial control by the use of chemical and optogenetic methods for inducing hook–anchor attachment. Moreover, the cargo is defined. Because several steps in vesicle creation are bypassed, we term it “hot-wiring.” We use hot-wired endocytosis to describe the functional interactions between clathrin and AP2. Two distinct sites on the β2 subunit, one on the hinge and the other on the appendage, are necessary and sufficient for functional clathrin engagement. PMID:28954824
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Zhang, Chen; Zhang, Tuo; Zou, Juan; Miller, Cassandra Lynn; Gorkhali, Rakshya; Yang, Jeong-Yeh; Schilmiller, Anthony; Wang, Shuo; Huang, Kenneth; Brown, Edward M; Moremen, Kelley W; Hu, Jian; Yang, Jenny J
2016-05-01
Ca(2+)-sensing receptors (CaSRs) modulate calcium and magnesium homeostasis and many (patho)physiological processes by responding to extracellular stimuli, including divalent cations and amino acids. We report the first crystal structure of the extracellular domain (ECD) of human CaSR bound with Mg(2+) and a tryptophan derivative ligand at 2.1 Å. The structure reveals key determinants for cooperative activation by metal ions and aromatic amino acids. The unexpected tryptophan derivative was bound in the hinge region between two globular ECD subdomains, and represents a novel high-affinity co-agonist of CaSR. The dissection of structure-function relations by mutagenesis, biochemical, and functional studies provides insights into the molecular basis of human diseases arising from CaSR mutations. The data also provide a novel paradigm for understanding the mechanism of CaSR-mediated signaling that is likely shared by the other family C GPCR [G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptor] members and can facilitate the development of novel CaSR-based therapeutics.
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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 region of the receptor. PMID:26441830
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Pourabed, Ehsan; Ghane Golmohamadi, Farzan; Soleymani Monfared, Peyman; Razavi, Seyed Morteza; Shobbar, Zahra-Sadat
2015-01-01
The basic leucine zipper (bZIP) family is one of the largest and most diverse transcription factors in eukaryotes participating in many essential plant processes. We identified 141 bZIP proteins encoded by 89 genes from the Hordeum vulgare genome. HvbZIPs were classified into 11 groups based on their DNA-binding motif. Amino acid sequence alignment of the HvbZIPs basic-hinge regions revealed some highly conserved residues within each group. The leucine zipper heptads were analyzed predicting their dimerization properties. 34 conserved motifs were identified outside the bZIP domain. Phylogenetic analysis indicated that major diversification within the bZIP family predated the monocot/dicot divergence, although intra-species duplication and parallel evolution seems to be occurred afterward. Localization of HvbZIPs on the barley chromosomes revealed that different groups have been distributed on seven chromosomes of barley. Six types of intron pattern were detected within the basic-hinge regions. Most of the detected cis-elements in the promoter and UTR sequences were involved in seed development or abiotic stress response. Microarray data analysis revealed differential expression pattern of HvbZIPs in response to ABA treatment, drought, and cold stresses and during barley grain development and germination. This information would be helpful for functional characterization of bZIP transcription factors in barley.
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The Function of UreB in Klebsiella aerogenes Urease†
Carter, Eric L.; Boer, Jodi L.; Farrugia, Mark A.; Flugga, Nicholas; Towns, Christopher L.; Hausinger, Robert P.
2011-01-01
Urease from Klebsiella aerogenes is composed of three subunits (UreA, UreB, and UreC) which assemble into a (UreABC)3 quaternary structure. UreC harbors the dinuclear nickel active site, whereas the functions of UreA and UreB remain unknown. UreD and UreF accessory proteins previously were suggested to reposition UreB and increase exposure of the nascent urease active site, thus facilitating metallocenter assembly. In this study, cells were engineered to separately produce (UreAC)3 or UreB, and the purified proteins were characterized. Monomeric UreB spontaneously binds to the trimeric heterodimer of UreA plus UreC to form (UreABC*)3 apoprotein, as shown by gel filtration chromatography, integration of electrophoretic gel band intensities, and mass spectrometry. Similar to authentic urease apoprotein, active enzyme is produced by incubation of (UreABC*)3 with Ni2+ and bicarbonate. Conversely, UreBΔ1-19, lacking the 19 residue potential hinge and tether to UreC, does not form a complex with (UreAC)3 and yields negligible levels of active enzyme when incubated under activation conditions with (UreAC)3. Comparison of activities and nickel contents for (UreAC)3, (UreABC*)3, and (UreABC)3 samples treated with Ni2+ and bicarbonate and then desalted indicates that UreB facilitates efficient incorporation of the metal into the active site and protects the bound metal from chelation. Amylose resin pull-down studies reveal that MBP-UreD (a fusion of maltose binding protein with UreD) forms complexes with (UreABC)3, (UreAC)3, and UreB in vivo, but not in vitro. By contrast, MBP-UreD does not form an in vivo complex with UreBΔ1-19. The soluble MBP-UreD:UreF:UreG complex binds in vitro to (UreABC)3, but not to (UreAC)3 or UreB. Together these data demonstrate that UreB facilitates the interaction of urease with accessory proteins during metallocenter assembly, with the N-terminal hinge and tether region being specifically required for this process. In addition to its role in urease activation, UreB enhances the stability of UreC against proteolytic cleavage. PMID:21939280
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Shape Memory Composite Hybrid Hinge
NASA Technical Reports Server (NTRS)
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 is reduced to below its glass transition temperature. After the deployable structure is launched in space, the SMC tube is reheated and the hinge is unfolded to deploy the structure. Based on test results, the hybrid hinge can achieve higher than 99.999% shape recovery. The hybrid hinge inherits all of the good characteristics of a tape-spring hinge such as simplicity, light weight, high deployment reliability, and high deployment precision. Conversely, it eliminates the deployment impact that has significantly limited the applications of a tape-spring hinge. The deployment dynamics of a hybrid hinge are in a slow and controllable fashion. The SMC tube of a hybrid hinge is a multifunctional component. It serves as a deployment mechanism during the deployment process, and also serves as a structural component after the hinge is fully deployed, which makes a hybrid hinge much stronger and stiffer than a tape-spring hinge. Unlike a mechanically deploying hinge that uses relatively moving components, a hybrid hinge depends on material deformation for its packing and deployment. It naturally eliminates the microdynamic phenomenon.
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Analysis of an electrohydraulic aircraft control surface servo and comparison with test results
NASA Technical Reports Server (NTRS)
Edwards, J. W.
1972-01-01
An analysis of an electrohydraulic aircraft control-surface system is made in which the system is modeled as a lumped, two-mass, spring-coupled system controlled by a servo valve. Both linear and nonlinear models are developed, and the effects of hinge-moment loading are included. Transfer functions of the system and approximate literal factors of the transfer functions for several cases are presented. The damping action of dynamic pressure feedback is analyzed. Comparisons of the model responses with results from tests made on a highly resonant rudder control-surface servo indicate the adequacy of the model. The effects of variations in hinge-moment loading are illustrated.
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Nam, Ki Hyun; Kurinov, Igor; Ke, Ailong
2011-09-02
Clustered regularly interspaced short palindromic repeats (CRISPR) and their associated protein genes (cas genes) are widespread in bacteria and archaea. They form a line of RNA-based immunity to eradicate invading bacteriophages and malicious plasmids. A key molecular event during this process is the acquisition of new spacers into the CRISPR loci to guide the selective degradation of the matching foreign genetic elements. Csn2 is a Nmeni subtype-specific cas gene required for new spacer acquisition. Here we characterize the Enterococcus faecalis Csn2 protein as a double-stranded (ds-) DNA-binding protein and report its 2.7 Å tetrameric ring structure. The inner circle of the Csn2 tetrameric ring is ∼26 Å wide and populated with conserved lysine residues poised for nonspecific interactions with ds-DNA. Each Csn2 protomer contains an α/β domain and an α-helical domain; significant hinge motion was observed between these two domains. Ca(2+) was located at strategic positions in the oligomerization interface. We further showed that removal of Ca(2+) ions altered the oligomerization state of Csn2, which in turn severely decreased its affinity for ds-DNA. In summary, our results provided the first insight into the function of the Csn2 protein in CRISPR adaptation by revealing that it is a ds-DNA-binding protein functioning at the quaternary structure level and regulated by Ca(2+) ions.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Nam, Ki Hyun; Kurinov, Igor; Ke, Ailong
Clustered regularly interspaced short palindromic repeats (CRISPR) and their associated protein genes (cas genes) are widespread in bacteria and archaea. They form a line of RNA-based immunity to eradicate invading bacteriophages and malicious plasmids. A key molecular event during this process is the acquisition of new spacers into the CRISPR loci to guide the selective degradation of the matching foreign genetic elements. Csn2 is a Nmeni subtype-specific cas gene required for new spacer acquisition. Here we characterize the Enterococcus faecalis Csn2 protein as a double-stranded (ds-) DNA-binding protein and report its 2.7 {angstrom} tetrameric ring structure. The inner circle ofmore » the Csn2 tetrameric ring is {approx}26 {angstrom} wide and populated with conserved lysine residues poised for nonspecific interactions with ds-DNA. Each Csn2 protomer contains an {alpha}/{beta} domain and an {alpha}-helical domain; significant hinge motion was observed between these two domains. Ca{sup 2+} was located at strategic positions in the oligomerization interface. We further showed that removal of Ca{sup 2+} ions altered the oligomerization state of Csn2, which in turn severely decreased its affinity for ds-DNA. In summary, our results provided the first insight into the function of the Csn2 protein in CRISPR adaptation by revealing that it is a ds-DNA-binding protein functioning at the quaternary structure level and regulated by Ca{sup 2+} ions.« less
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Campelo, Diana; Lautier, Thomas; Urban, Philippe; Esteves, Francisco; Bozonnet, Sophie; Truan, Gilles; Kranendonk, Michel
2017-01-01
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. PMID:29163152
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Aerodynamic coefficients in generalized unsteady thin airfoil theory
NASA Technical Reports Server (NTRS)
Williams, M. H.
1980-01-01
Two cases are considered: (1) rigid body motion of an airfoil-flap combination consisting of vertical translation of given amplitude, rotation of given amplitude about a specified axis, and rotation of given amplitude of the control surface alone about its hinge; the upwash for this problem is defined mathematically; and (2) sinusoidal gust of given amplitude and wave number, for which the upwash is defined mathematically. Simple universal formulas are presented for the most important aerodynamic coefficients in unsteady thin airfoil theory. The lift and moment induced by a generalized gust are evaluated explicitly in terms of the gust wavelength. Similarly, in the control surface problem, the lift, moment, and hinge moments are given as explicit algebraic functions of hinge location. These results can be used together with any of the standard numerical inversion routines for the elementary loads (pitch and heave).
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Code of Federal Regulations, 2012 CFR
2012-01-01
... STANDARDS: TRANSPORT CATEGORY AIRPLANES Design and Construction Control Surfaces § 25.657 Hinges. (a) For control surface hinges, including ball, roller, and self-lubricated bearing hinges, the approved rating of... hinge line. [Amdt. 25-23, 35 FR 5674, Apr. 8, 1970] Control Systems ...
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Code of Federal Regulations, 2010 CFR
2010-01-01
... STANDARDS: TRANSPORT CATEGORY AIRPLANES Design and Construction Control Surfaces § 25.657 Hinges. (a) For control surface hinges, including ball, roller, and self-lubricated bearing hinges, the approved rating of... hinge line. [Amdt. 25-23, 35 FR 5674, Apr. 8, 1970] Control Systems ...
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Code of Federal Regulations, 2011 CFR
2011-01-01
... STANDARDS: TRANSPORT CATEGORY AIRPLANES Design and Construction Control Surfaces § 25.657 Hinges. (a) For control surface hinges, including ball, roller, and self-lubricated bearing hinges, the approved rating of... hinge line. [Amdt. 25-23, 35 FR 5674, Apr. 8, 1970] Control Systems ...
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Code of Federal Regulations, 2014 CFR
2014-01-01
... STANDARDS: TRANSPORT CATEGORY AIRPLANES Design and Construction Control Surfaces § 25.657 Hinges. (a) For control surface hinges, including ball, roller, and self-lubricated bearing hinges, the approved rating of... hinge line. [Amdt. 25-23, 35 FR 5674, Apr. 8, 1970] Control Systems ...
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Self-Folded Gripper-Like Architectures from Stimuli-Responsive Bilayers.
Abdullah, Arif M; Li, Xiuling; Braun, Paul V; Rogers, John A; Hsia, K Jimmy
2018-06-19
Self-folding microgrippers are an emerging class of smart structures that have widespread applications in medicine and micro/nanomanipulation. To achieve their functionalities, these architectures rely on spatially patterned hinges to transform into 3D configurations in response to an external stimulus. Incorporating hinges into the devices requires the processing of multiple layers which eventually increases the fabrication costs and actuation complexities. The goal of this work is to demonstrate that it is possible to achieve gripper-like configurations in an on-demand manner from simple planar bilayers that do not require hinges for their actuation. Finite element modeling of bilayers is performed to understand the mechanics behind their stimuli-responsive shape transformation behavior. The model predictions are then experimentally validated and axisymmetric gripper-like shapes are realized using millimeter-scale poly(dimethylsiloxane) bilayers that undergo differential swelling in organic solvents. Owing to the nature of the computational scheme which is independent of length scales and material properties, the guidelines reported here would be applicable to a diverse array of gripping systems and functional devices. Thus, this work not only demonstrates a simple route to fabricate functional microgrippers but also contributes to self-assembly in general. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Ababou, Abdessamad; Rostkova, Elena; Mistry, Shreena; Le Masurier, Clare; Gautel, Mathias; Pfuhl, Mark
2008-12-19
Myosin binding protein C (MyBP-C) is a thick filament protein involved in the regulation of muscle contraction. Mutations in the gene for MyBP-C are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. It is assumed that the function of MyBP-C is to act as a tether that fixes the S1 heads in a resting position and that phosphorylation releases the S1 heads into an active state. Here, we report the structure and binding properties of domain C1. Using a combination of site-directed mutagenesis and NMR interaction experiments, we identified the binding site of domain C1 in the immediate vicinity of the S1-S2 hinge, very close to the light chains. In addition, we identified a zinc binding site on domain C1 in close proximity to the S2 binding site. Its zinc binding affinity (K(d) of approximately 10-20 microM) might not be sufficient for a physiological effect. However, the familial hypertrophic cardiomyopathy-related mutation of one of the zinc ligands, glutamine 210 to histidine, will significantly increase the binding affinity, suggesting that this mutation may affect S2 binding. The close proximity of the C1 binding site to the hinge, the light chains and the S1 heads also provides an explanation for recent observations that (a) shorter fragments of MyBP-C unable to act as a tether still have an effect on the actomyosin ATPase and (b) as to why the myosin head positions in phosphorylated wild-type mice and MyBP-C knockout mice are so different: Domain C1 bound to the S1-S2 hinge is able to manipulate S1 head positions, thus influencing force generation without tether. The potentially extensive extra interactions of C1 are expected to keep it in place, while phosphorylation dislodges the C1-C2 linker and domain C2. As a result, the myosin heads would always be attached to a tether that has phosphorylation-dependent length regulation.
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Ababou, Abdessamad; Rostkova, Elena; Mistry, Shreena; Masurier, Clare Le; Gautel, Mathias; Pfuhl, Mark
2008-01-01
Myosin binding protein C (MyBP-C) is a thick filament protein involved in the regulation of muscle contraction. Mutations in the gene for MyBP-C are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. It is assumed that the function of MyBP-C is to act as a tether that fixes the S1 heads in a resting position and that phosphorylation releases the S1 heads into an active state. Here, we report the structure and binding properties of domain C1. Using a combination of site-directed mutagenesis and NMR interaction experiments, we identified the binding site of domain C1 in the immediate vicinity of the S1–S2 hinge, very close to the light chains. In addition, we identified a zinc binding site on domain C1 in close proximity to the S2 binding site. Its zinc binding affinity (Kd of approximately 10–20 μM) might not be sufficient for a physiological effect. However, the familial hypertrophic cardiomyopathy-related mutation of one of the zinc ligands, glutamine 210 to histidine, will significantly increase the binding affinity, suggesting that this mutation may affect S2 binding. The close proximity of the C1 binding site to the hinge, the light chains and the S1 heads also provides an explanation for recent observations that (a) shorter fragments of MyBP-C unable to act as a tether still have an effect on the actomyosin ATPase and (b) as to why the myosin head positions in phosphorylated wild-type mice and MyBP-C knockout mice are so different: Domain C1 bound to the S1–S2 hinge is able to manipulate S1 head positions, thus influencing force generation without tether. The potentially extensive extra interactions of C1 are expected to keep it in place, while phosphorylation dislodges the C1–C2 linker and domain C2. As a result, the myosin heads would always be attached to a tether that has phosphorylation-dependent length regulation. PMID:18926831
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Helmstaedt, Kerstin; Heinrich, Gabriele; Lipscomb, William N.; Braus, Gerhard H.
2002-01-01
The yeast chorismate mutase is regulated by tyrosine as feedback inhibitor and tryptophan as crosspathway activator. The monomer consists of a catalytic and a regulatory domain covalently linked by the loop L220s (212–226), which functions as a molecular hinge. Two monomers form the active dimeric enzyme stabilized by hydrophobic interactions in the vicinity of loop L220s. The role of loop L220s and its environment for enzyme regulation, dimerization, and stability was analyzed. Substitution of yeast loop L220s in place of the homologous loop from the corresponding and similarly regulated Aspergillus enzyme (and the reverse substitution) changed tyrosine inhibition to activation. Yeast loop L220s substituted into the Aspergillus enzyme resulted in a tryptophan-inhibitable enzyme. Monomeric yeast chorismate mutases could be generated by substituting two hydrophobic residues in and near the hinge region. The resulting Thr-212→Asp–Phe-28→Asp enzyme was as stable as wild type, but lost allosteric regulation and showed reduced catalytic activity. These results underline the crucial role of this molecular hinge for inhibition, activation, quaternary structure, and stability of yeast chorismate mutase. PMID:11997452
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Magnetic Actuation of Self-Assembled DNA Hinges
NASA Astrophysics Data System (ADS)
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.
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Archaea Signal Recognition Particle Shows the Way
Zwieb, Christian; Bhuiyan, Shakhawat
2010-01-01
Archaea SRP is composed of an SRP RNA molecule and two bound proteins named SRP19 and SRP54. Regulated by the binding and hydrolysis of guanosine triphosphates, the RNA-bound SRP54 protein transiently associates not only with the hydrophobic signal sequence as it emerges from the ribosomal exit tunnel, but also interacts with the membrane-associated SRP receptor (FtsY). Comparative analyses of the archaea genomes and their SRP component sequences, combined with structural and biochemical data, support a prominent role of the SRP RNA in the assembly and function of the archaea SRP. The 5e motif, which in eukaryotes binds a 72 kilodalton protein, is preserved in most archaea SRP RNAs despite the lack of an archaea SRP72 homolog. The primary function of the 5e region may be to serve as a hinge, strategically positioned between the small and large SRP domain, allowing the elongated SRP to bind simultaneously to distant ribosomal sites. SRP19, required in eukaryotes for initiating SRP assembly, appears to play a subordinate role in the archaea SRP or may be defunct. The N-terminal A region and a novel C-terminal R region of the archaea SRP receptor (FtsY) are strikingly diverse or absent even among the members of a taxonomic subgroup. PMID:20672053
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Code of Federal Regulations, 2014 CFR
2014-01-01
... STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY AIRPLANES Design and Construction Control Surfaces § 23.657 Hinges. (a) Control surface hinges, except ball and roller bearing hinges, must have a...
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Code of Federal Regulations, 2012 CFR
2012-01-01
... STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY AIRPLANES Design and Construction Control Surfaces § 23.657 Hinges. (a) Control surface hinges, except ball and roller bearing hinges, must have a...
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Code of Federal Regulations, 2010 CFR
2010-01-01
... STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY AIRPLANES Design and Construction Control Surfaces § 23.657 Hinges. (a) Control surface hinges, except ball and roller bearing hinges, must have a...
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Code of Federal Regulations, 2011 CFR
2011-01-01
... STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY AIRPLANES Design and Construction Control Surfaces § 23.657 Hinges. (a) Control surface hinges, except ball and roller bearing hinges, must have a...
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Code of Federal Regulations, 2013 CFR
2013-01-01
... STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY AIRPLANES Design and Construction Control Surfaces § 23.657 Hinges. (a) Control surface hinges, except ball and roller bearing hinges, must have a...
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Structural and Biochemical Studies of ALIX/AlP1 and Its Role in Retrovirus Budding
DOE Office of Scientific and Technical Information (OSTI.GOV)
Fisher,R.; Chung, H.; Zhai, Q.
2007-01-01
ALIX/AIP1 functions in enveloped virus budding, endosomal protein sorting, and many other cellular processes. Retroviruses, including HIV-1, SIV, and EIAV, bind and recruit ALIX through YPXnL late-domain motifs (X = any residue; n = 1-3). Crystal structures reveal that human ALIX is composed of an N-terminal Bro1 domain and a central domain that is composed of two extended three-helix bundles that form elongated arms that fold back into a 'V.'. The structures also reveal conformational flexibility in the arms that suggests that the V domain may act as a flexible hinge in response to ligand binding. YPXnL late domains bindmore » in a conserved hydrophobic pocket on the second arm near the apex of the V, whereas CHMP4/ESCRT-III proteins bind a conserved hydrophobic patch on the Bro1 domain, and both interactions are required for virus budding. ALIX therefore serves as a flexible, extended scaffold that connects retroviral Gag proteins to ESCRT-III and other cellular-budding machinery.« less
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A simple electrostatic switch important in the activation of type I protein kinase A by cyclic AMP.
Vigil, Dominico; Lin, Jung-Hsin; Sotriffer, Christoph A; Pennypacker, Juniper K; McCammon, J Andrew; Taylor, Susan S
2006-01-01
Cyclic AMP activates protein kinase A by binding to an inhibitory regulatory (R) subunit and releasing inhibition of the catalytic (C) subunit. Even though crystal structures of regulatory and catalytic subunits have been solved, the precise molecular mechanism by which cyclic AMP activates the kinase remains unknown. The dynamic properties of the cAMP binding domain in the absence of cAMP or C-subunit are also unknown. Here we report molecular-dynamics simulations and mutational studies of the RIalpha R-subunit that identify the C-helix as a highly dynamic switch which relays cAMP binding to the helical C-subunit binding regions. Furthermore, we identify an important salt bridge which links cAMP binding directly to the C-helix that is necessary for normal activation. Additional mutations show that a hydrophobic "hinge" region is not as critical for the cross-talk in PKA as it is in the homologous EPAC protein, illustrating how cAMP can control diverse functions using the evolutionarily conserved cAMP-binding domains.
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Yeo, Giselle C; Tarakanova, Anna; Baldock, Clair; Wise, Steven G; Buehler, Markus J; Weiss, Anthony S
2016-02-01
The assembly of the tropoelastin monomer into elastin is vital for conferring elasticity on blood vessels, skin, and lungs. Tropoelastin has dual needs for flexibility and structure in self-assembly. We explore the structure-dynamics-function interplay, consider the duality of molecular order and disorder, and identify equally significant functional contributions by local and global structures. To study these organizational stratifications, we perturb a key hinge region by expressing an exon that is universally spliced out in human tropoelastins. We find a herniated nanostructure with a displaced C terminus and explain by molecular modeling that flexible helices are replaced with substantial β sheets. We see atypical higher-order cross-linking and inefficient assembly into discontinuous, thick elastic fibers. We explain this dysfunction by correlating local and global structural effects with changes in the molecule's assembly dynamics. This work has general implications for our understanding of elastomeric proteins, which balance disordered regions with defined structural modules at multiple scales for functional assembly.
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Pivot design in bileaflet valves.
Vallana, F; Rinaldi, S; Galletti, P M; Nguyen, A; Piwnica, A
1992-01-01
The design criteria leading to the development of a new bileaflet valve (Sorin Bicarbon) were derived from the analysis of functional requirements, the performance of existing prostheses, and the availability of an advanced carbon coating technology (Carbofilm). The hinge is the critical element affecting fluid dynamics, durability, and thrombus formation in bileaflet valves. A comparative study of three existing models led to a new hinge design that was based on coupling two spheric surfaces with different radii of curvature (leaflet pivot and hinge recess) and obtained by electroerosion into a Carbofilm-coated metallic housing. In this valve, the point of contact moves continuously by rolling, not sliding. This minimizes friction and wear and allows uninterrupted washing of the blood exposed surfaces even during diastole (a finding established in patients using transesophageal echocardiography). Tricuspid implantation without anticoagulation in 33 sheep did not lead to thrombotic events (follow-up, 40-400 days). In the first 36 clinical implants observed for 15 months (mitral position, size 29; two unrelated deaths), the mean diastolic gradient by echo Doppler was 4 +/- 1.25 mmHg; the functional area was 3.2 +/- 0.6 cm2. No leaflet fracture and no thrombotic or embolic complications were observed clinically using a standard anticoagulant regimen.
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The flexibility and dynamics of protein disulfide isomerase
Wells, Stephen A.; Emilio Jimenez‐Roldan, J.; Bhattacharyya, Moitrayee; Vishweshwara, Saraswathi; Freedman, Robert B.
2016-01-01
ABSTRACT We have studied the mobility of the multidomain folding catalyst, protein disulfide isomerase (PDI), by a coarse‐graining approach based on flexibility. We analyze our simulations of yeast PDI (yPDI) using measures of backbone movement, relative positions and orientations of domains, and distances between functional sites. We find that there is interdomain flexibility at every interdomain junction but these show very different characteristics. The extent of interdomain flexibility is such that yPDI's two active sites can approach much more closely than is found in crystal structures—and indeed hinge motion to bring these sites into proximity is the lowest energy normal mode of motion of the protein. The flexibility predicted for yPDI (based on one structure) includes the other known conformation of yPDI and is consistent with (i) the mobility observed experimentally for mammalian PDI and (ii) molecular dynamics. We also observe intradomain flexibility and clear differences between the domains in their propensity for internal motion. Our results suggest that PDI flexibility enables it to interact with many different partner molecules of widely different sizes and shapes, and highlights considerable similarities of yPDI and mammalian PDI. Proteins 2016; 84:1776–1785. © 2016 Wiley Periodicals, Inc. PMID:27616289
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The Structure of Gene Product 6 of Bacteriophage T4, the Hinge-Pin of the Baseplate
DOE Office of Scientific and Technical Information (OSTI.GOV)
Aksyuk, Anastasia A.; Leiman, Petr G.; Shneider, Mikhail M.
2009-07-21
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 wedgesmore » 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 {approx}15{sup o}, accounting for a 10 {angstrom} radial increase in the diameter of the gp6 ring.« less
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Seidel, Lisa; Zarzycka, Barbara; Zaidi, Saheem A; Katritch, Vsevolod; Coin, Irene
2017-01-01
The activation mechanism of class B G-protein-coupled receptors (GPCRs) remains largely unknown. To characterize conformational changes induced by peptide hormones, we investigated interactions of the class B corticotropin-releasing factor receptor type 1 (CRF1R) with two peptide agonists and three peptide antagonists obtained by N-truncation of the agonists. Surface mapping with genetically encoded photo-crosslinkers and pair-wise crosslinking revealed distinct footprints of agonists and antagonists on the transmembrane domain (TMD) of CRF1R and identified numerous ligand-receptor contact sites, directly from the intact receptor in live human cells. The data enabled generating atomistic models of CRF- and CRF(12-41)-bound CRF1R, further explored by molecular dynamics simulations. We show that bound agonist and antagonist adopt different folds and stabilize distinct TMD conformations, which involves bending of helices VI and VII around flexible glycine hinges. Conservation of these glycine hinges among all class B GPCRs suggests their general role in activation of these receptors. DOI: http://dx.doi.org/10.7554/eLife.27711.001 PMID:28771403
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Sarin, L Peter; Wright, Sam; Chen, Qing; Degerth, Linda H; Stuart, David I; Grimes, Jonathan M; Bamford, Dennis H; Poranen, Minna M
2012-10-10
Double-stranded RNA viruses encode a single protein species containing RNA-dependent RNA polymerase (RdRP) motifs. This protein is responsible for RNA transcription and replication. The architecture of viral RdRPs resembles that of a cupped right hand with fingers, palm and thumb domains. Those using de novo initiation have a flexible structural elaboration that constitutes the priming platform. Here we investigate the properties of the C-terminal priming domain of bacteriophage ϕ6 to get insights into the role of an extended loop connecting this domain to the main body of the polymerase. Proteolyzed ϕ6 RdRP that possesses a nick in the hinge region of this loop was better suited for de novo initiation. The clipped C-terminus remained associated with the main body of the polymerase via the anchor helix. The structurally flexible hinge region appeared to be involved in the control of priming platform movement. Moreover, we detected abortive initiation products for a bacteriophage RdRP. Copyright © 2012 Elsevier Inc. All rights reserved.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Han, Seungil; Mistry, Anil; Chang, Jeanne S.
Proline-rich tyrosine kinase 2 (PYK2) is a cytoplasmic, non-receptor tyrosine kinase implicated in multiple signaling pathways. It is a negative regulator of osteogenesis and considered a viable drug target for osteoporosis treatment. The high-resolution structures of the human PYK2 kinase domain with different inhibitor complexes establish the conventional bilobal kinase architecture and show the conformational variability of the DFG loop. The basis for the lack of selectivity for the classical kinase inhibitor, PF-431396, within the FAK family is explained by our structural analyses. Importantly, the novel DFG-out conformation with two diarylurea inhibitors (BIRB796, PF-4618433) reveals a distinct subclass of non-receptormore » tyrosine kinases identifiable by the gatekeeper Met-502 and the unique hinge loop conformation of Leu-504. This is the first example of a leucine residue in the hinge loop that blocks the ATP binding site in the DFG-out conformation. Our structural, biophysical, and pharmacological studies suggest that the unique features of the DFG motif, including Leu-504 hinge-loop variability, can be exploited for the development of selective protein kinase inhibitors.« less
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Non-degradative Ubiquitination of Protein Kinases
Ball, K. Aurelia; Johnson, Jeffrey R.; Lewinski, Mary K.; Guatelli, John; Verschueren, Erik; Krogan, Nevan J.; Jacobson, Matthew P.
2016-01-01
Growing evidence supports other regulatory roles for protein ubiquitination in addition to serving as a tag for proteasomal degradation. In contrast to other common post-translational modifications, such as phosphorylation, little is known about how non-degradative ubiquitination modulates protein structure, dynamics, and function. Due to the wealth of knowledge concerning protein kinase structure and regulation, we examined kinase ubiquitination using ubiquitin remnant immunoaffinity enrichment and quantitative mass spectrometry to identify ubiquitinated kinases and the sites of ubiquitination in Jurkat and HEK293 cells. We find that, unlike phosphorylation, ubiquitination most commonly occurs in structured domains, and on the kinase domain, ubiquitination is concentrated in regions known to be important for regulating activity. We hypothesized that ubiquitination, like other post-translational modifications, may alter the conformational equilibrium of the modified protein. We chose one human kinase, ZAP-70, to simulate using molecular dynamics with and without a monoubiquitin modification. In Jurkat cells, ZAP-70 is ubiquitinated at several sites that are not sensitive to proteasome inhibition and thus may have other regulatory roles. Our simulations show that ubiquitination influences the conformational ensemble of ZAP-70 in a site-dependent manner. When monoubiquitinated at K377, near the C-helix, the active conformation of the ZAP-70 C-helix is disrupted. In contrast, when monoubiquitinated at K476, near the kinase hinge region, an active-like ZAP-70 C-helix conformation is stabilized. These results lead to testable hypotheses that ubiquitination directly modulates kinase activity, and that ubiquitination is likely to alter structure, dynamics, and function in other protein classes as well. PMID:27253329
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Segment swapping aided the evolution of enzyme function: The case of uroporphyrinogen III synthase.
Szilágyi, András; Györffy, Dániel; Závodszky, Péter
2017-01-01
In an earlier study, we showed that two-domain segment-swapped proteins can evolve by domain swapping and fusion, resulting in a protein with two linkers connecting its domains. We proposed that a potential evolutionary advantage of this topology may be the restriction of interdomain motions, which may facilitate domain closure by a hinge-like movement, crucial for the function of many enzymes. Here, we test this hypothesis computationally on uroporphyrinogen III synthase, a two-domain segment-swapped enzyme essential in porphyrin metabolism. To compare the interdomain flexibility between the wild-type, segment-swapped enzyme (having two interdomain linkers) and circular permutants of the same enzyme having only one interdomain linker, we performed geometric and molecular dynamics simulations for these species in their ligand-free and ligand-bound forms. We find that in the ligand-free form, interdomain motions in the wild-type enzyme are significantly more restricted than they would be with only one interdomain linker, while the flexibility difference is negligible in the ligand-bound form. We also estimated the entropy costs of ligand binding associated with the interdomain motions, and find that the change in domain connectivity due to segment swapping results in a reduction of this entropy cost, corresponding to ∼20% of the total ligand binding free energy. In addition, the restriction of interdomain motions may also help the functional domain-closure motion required for catalysis. This suggests that the evolution of the segment-swapped topology facilitated the evolution of enzyme function for this protein by influencing its dynamic properties. Proteins 2016; 85:46-53. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
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Crystal Structure of a Coiled-Coil Domain from Human ROCK I
Tu, Daqi; Li, Yiqun; Song, Hyun Kyu; Toms, Angela V.; Gould, Christopher J.; Ficarro, Scott B.; Marto, Jarrod A.; Goode, Bruce L.; Eck, Michael J.
2011-01-01
The small GTPase Rho and one of its targets, Rho-associated kinase (ROCK), participate in a variety of actin-based cellular processes including smooth muscle contraction, cell migration, and stress fiber formation. The ROCK protein consists of an N-terminal kinase domain, a central coiled-coil domain containing a Rho binding site, and a C-terminal pleckstrin homology domain. Here we present the crystal structure of a large section of the central coiled-coil domain of human ROCK I (amino acids 535–700). The structure forms a parallel α-helical coiled-coil dimer that is structurally similar to tropomyosin, an actin filament binding protein. There is an unusual discontinuity in the coiled-coil; three charged residues (E613, R617 and D620) are positioned at what is normally the hydrophobic core of coiled-coil packing. We speculate that this conserved irregularity could function as a hinge that allows ROCK to adopt its autoinhibited conformation. PMID:21445309
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Sharma, Sulabha; Kharshiing, Eros; Srinivas, Ankanagari; Zikihara, Kazunori; Tokutomi, Satoru; Nagatani, Akira; Fukayama, Hiroshi; Bodanapu, Reddaiah; Behera, Rajendra K.; Sreelakshmi, Yellamaraju; Sharma, Rameshwar
2014-01-01
In higher plants, blue light (BL) phototropism is primarily controlled by the phototropins, which are also involved in stomatal movement and chloroplast relocation. These photoresponses are mediated by two phototropins, phot1 and phot2. Phot1 mediates responses with higher sensitivity than phot2, and phot2 specifically mediates chloroplast avoidance and dark positioning responses. Here, we report the isolation and characterization of a Nonphototropic seedling1 (Nps1) mutant of tomato (Solanum lycopersicum). The mutant is impaired in low-fluence BL responses, including chloroplast accumulation and stomatal opening. Genetic analyses show that the mutant locus is dominant negative in nature. In dark-grown seedlings of the Nps1 mutant, phot1 protein accumulates at a highly reduced level relative to the wild type and lacks BL-induced autophosphorylation. The mutant harbors a single glycine-1484-to-alanine transition in the Hinge1 region of a phot1 homolog, resulting in an arginine-to-histidine substitution (R495H) in a highly conserved A′α helix proximal to the light-oxygen and voltage2 domain of the translated gene product. Significantly, the R495H substitution occurring in the Hinge1 region of PHOT1 abolishes its regulatory activity in Nps1 seedlings, thereby highlighting the functional significance of the A′α helix region in phototropic signaling of tomato. PMID:24515830
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Revealing time bunching effect in single-molecule enzyme conformational dynamics.
Lu, H Peter
2011-04-21
In this perspective, we focus our discussion on how the single-molecule spectroscopy and statistical analysis are able to reveal enzyme hidden properties, taking the study of T4 lysozyme as an example. Protein conformational fluctuations and dynamics play a crucial role in biomolecular functions, such as in enzymatic reactions. Single-molecule spectroscopy is a powerful approach to analyze protein conformational dynamics under physiological conditions, providing dynamic perspectives on a molecular-level understanding of protein structure-function mechanisms. Using single-molecule fluorescence spectroscopy, we have probed T4 lysozyme conformational motions under the hydrolysis reaction of a polysaccharide of E. coli B cell walls by monitoring the fluorescence resonant energy transfer (FRET) between a donor-acceptor probe pair tethered to T4 lysozyme domains involving open-close hinge-bending motions. Based on the single-molecule spectroscopic results, molecular dynamics simulation, a random walk model analysis, and a novel 2D statistical correlation analysis, we have revealed a time bunching effect in protein conformational motion dynamics that is critical to enzymatic functions. Bunching effect implies that conformational motion times tend to bunch in a finite and narrow time window. We show that convoluted multiple Poisson rate processes give rise to the bunching effect in the enzymatic reaction dynamics. Evidently, the bunching effect is likely common in protein conformational dynamics involving in conformation-gated protein functions. In this perspective, we will also discuss a new approach of 2D regional correlation analysis capable of analyzing fluctuation dynamics of complex multiple correlated and anti-correlated fluctuations under a non-correlated noise background. Using this new method, we are able to map out any defined segments along the fluctuation trajectories and determine whether they are correlated, anti-correlated, or non-correlated; after which, a cross correlation analysis can be applied for each specific segment to obtain a detailed fluctuation dynamics analysis.
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2005-05-01
an impaired activity (see report of 2003). We obtained an EGFP fusion from Dr. Karen Knudsen (Ohio University, Cincinatti) in which a Gly-Ala linker ... Smad3 after its acetylation. The mutation of this lysine to glutamine or threonine (mimics acetylation), when expressed in DU145 cells promoted cell...forms. A Gly-Ala linker between the two proteins is necessary, since a direct fusion protein was largely impaired in its activity (not shown). 6. The
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Retroreflector for Photonic Doppler Velocimetry
2009-03-01
devices . . . . . . . . . . . . . . 58 3.24 SOI device after DRIE and hinge deposition . . . . . . . . . . . . . 59 3.25 MEMS micromirror etch hole layout...61 3.26 Amplitude transmittance functions for MEMS micromirrors . . . . 62 3.27 Diffraction pattern of a square flat...weight of micromirror . . . . . . . . . . . . . . . . . 54 tA amplitude transmittance function . . . . . . . . . . . . . . . . . . . 62 Rspec specular
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Thin film solar cell inflatable ultraviolet rigidizable deployment hinge
NASA Technical Reports Server (NTRS)
Simburger, Edward J. (Inventor); Giants, Thomas W. (Inventor); Perry, Alan R. (Inventor); Rawal, Suraj (Inventor); Lin, John K. H. (Inventor); Matsumoto, James H. (Inventor); Garcia, III, Alec (Inventor); Marshall, Craig H. (Inventor); Day, Jonathan Robert (Inventor); Kerslake, Thomas W. (Inventor)
2010-01-01
A flexible inflatable hinge includes curable resin for rigidly positioning panels of solar cells about the hinge in which wrap around contacts and flex circuits are disposed for routing power from the solar cells to the power bus further used for grounding the hinge. An indium tin oxide and magnesium fluoride coating is used to prevent static discharge while being transparent to ultraviolet light that cures the embedded resin after deployment for rigidizing the inflatable hinge.
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Guan, Hexin; Zheng, Zhengui; Grey, Paris H; Li, Yuhua; Oppenheimer, David G
2011-05-01
Floral transition is a critical and strictly regulated developmental process in plants. Mutations in Arabidopsis LIKE HETEROCHROMATIN PROTEIN 1 (AtLHP1)/TERMINAL FLOWER 2 (TFL2) result in early and terminal flowers. Little is known about the gene expression, function and evolution of plant LHP1 homologs, except for Arabidopsis LHP1. In this study, the conservation and divergence of plant LHP1 protein sequences was analyzed by sequence alignments and phylogeny. LHP1 expression patterns were compared among taxa that occupy pivotal phylogenetic positions. Several relatively conserved new motifs/regions were identified among LHP1 homologs. Phylogeny of plant LHP1 proteins agreed with established angiosperm relationships. In situ hybridization unveiled conserved expression of plant LHP1 in the axillary bud/tiller, vascular bundles, developing stamens, and carpels. Unlike AtLHP1, cucumber CsLHP1-2, sugarcane SoLHP1 and maize ZmLHP1, rice OsLHP1 is not expressed in the shoot apical meristem (SAM) and the OsLHP1 transcript level is consistently low in shoots. "Unequal crossover" might have contributed to the divergence in the N-terminal and hinge region lengths of LHP1 homologs. We propose an "insertion-deletion" model for soybean (Glycine max L.) GmLHP1s evolution. Plant LHP1 homologs are more conserved than previously expected, and may favor vegetative meristem identity and primordia formation. OsLHP1 may not function in rice SAM during floral induction.
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NASA Astrophysics Data System (ADS)
Qiu, Zhi-cheng; Wang, Xian-feng; Zhang, Xian-Min; Liu, Jin-guo
2018-07-01
A novel non-contact vibration measurement method using binocular vision sensors is proposed for piezoelectric flexible hinged plate. Decoupling methods of the bending and torsional low frequency vibration on measurement and driving control are investigated, using binocular vision sensors and piezoelectric actuators. A radial basis function neural network controller (RBFNNC) is designed to suppress both the larger and the smaller amplitude vibrations. To verify the non-contact measurement method and the designed controller, an experimental setup of the flexible hinged plate with binocular vision is constructed. Experiments on vibration measurement and control are conducted by using binocular vision sensors and the designed RBFNNC controllers, compared with the classical proportional and derivative (PD) control algorithm. The experimental measurement results demonstrate that the binocular vision sensors can detect the low-frequency bending and torsional vibration effectively. Furthermore, the designed RBF can suppress the bending vibration more quickly than the designed PD controller owing to the adjustment of the RBF control, especially for the small amplitude residual vibrations.
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Morphologic-echocardiographic correlates of Ebstein's malformation.
Rusconi, P G; Zuberbuhler, J R; Anderson, R H; Rigby, M L
1991-07-01
The cross-sectional echocardiographic findings were analysed retrospectively in 26 patients with Ebstein's malformation in the light of studies of autopsied specimens from different patients showing this lesion. The salient anatomical feature in diagnosis is the finding of the hinge point of the septal and mural leaflets of the valve within the inlet component of the right ventricle rather than at the atrioventricular junction. The other important feature is the nature of the distal attachment of the leaflets, particularly the anterosuperior one, which can either be in focal or linear fashion. The hinge point of the septal leaflet was noted echocardiographically to be displaced in 19 patients but, significantly, the leaflet was absent in the other seven. Also significant was that the hinge point of the mural leaflet at the crux had been visualized in only 15 of the patients. The anterosuperior leaflet had a distal linear attachment in 20 of the patients, with the anteroseptal commissure becoming a keyhole in six of these through which blood passed to the functional right ventricle. The valve remained a competent structure, even though closing at the junction of atrialized and functional components of the right ventricle rather than at the atrioventricular junction. Cross-sectional echocardiography is the technique of choice with which to display the salient morphological features of Ebstein's malformation.
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Note: Design and capability verification of fillet triangle flexible support
NASA Astrophysics Data System (ADS)
Wang, Tao; San, Xiao-Gang; Gao, Shi-Jie; Wang, Jing; Ni, Ying-Xue; Sang, Zhi-Xin
2017-12-01
By increasing the section thickness of a triangular flexible hinge, this study focuses on optimal selection of parameters of fillet triangle flexible hinges and flexible support. Based on Castigliano's second theorem, the flexibility expression of the fillet triangle flexible hinge was derived. Then, the case design is performed, and the comparison of three types of flexible hinges with this type of flexible hinge was carried out. The finite element models of fillet triangle flexible hinges and flexible support were built, and then the simulation results of performance parameters were calculated. Finally, the experiment platform was established to validate analysis results. The maximum error is less than 8%, which verifies the accuracy of the simulation process and equations derived; also the fundamental frequency fits the requirements of the system. The fillet triangle flexible hinge is proved to have the advantages of high precision and low flexibility.
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Note: Design and capability verification of fillet triangle flexible support.
Wang, Tao; San, Xiao-Gang; Gao, Shi-Jie; Wang, Jing; Ni, Ying-Xue; Sang, Zhi-Xin
2017-12-01
By increasing the section thickness of a triangular flexible hinge, this study focuses on optimal selection of parameters of fillet triangle flexible hinges and flexible support. Based on Castigliano's second theorem, the flexibility expression of the fillet triangle flexible hinge was derived. Then, the case design is performed, and the comparison of three types of flexible hinges with this type of flexible hinge was carried out. The finite element models of fillet triangle flexible hinges and flexible support were built, and then the simulation results of performance parameters were calculated. Finally, the experiment platform was established to validate analysis results. The maximum error is less than 8%, which verifies the accuracy of the simulation process and equations derived; also the fundamental frequency fits the requirements of the system. The fillet triangle flexible hinge is proved to have the advantages of high precision and low flexibility.
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Concealed hinge permits flush mounting of doors and hatches
NASA Technical Reports Server (NTRS)
Holman, E. V.
1966-01-01
Hinge assembly permits flush mounting of doors and hatches of considerable thickness so that the axis of instant rotation, produced by the hinge, lies outside the panel surface and beyond the perimeter adjacent to the hinge. In operation, motion of the assembly is initially parallel, changing to angular after clearing the panel perimeter.
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Nakamura, R; Komatsu, N; Fujita, K; Kuroda, K; Takahashi, M; Omi, R; Katsuki, Y; Tsuchiya, H
2017-10-01
Open wedge high tibial osteotomy (OWHTO) for medial-compartment osteoarthritis of the knee can be complicated by intra-operative lateral hinge fracture (LHF). We aimed to establish the relationship between hinge position and fracture types, and suggest an appropriate hinge position to reduce the risk of this complication. Consecutive patients undergoing OWHTO were evaluated on coronal multiplanar reconstruction CT images. Hinge positions were divided into five zones in our new classification, by their relationship to the proximal tibiofibular joint (PTFJ). Fractures were classified into types I, II, and III according to the Takeuchi classification. Among 111 patients undergoing OWHTOs, 22 sustained lateral hinge fractures. Of the 89 patients without fractures, 70 had hinges in the zone within the PTFJ and lateral to the medial margin of the PTFJ (zone WL), just above the PTFJ. Among the five zones, the relative risk of unstable fracture was significantly lower in zone WL (relative risk 0.24, confidence interval 0.17 to 0.34). Zone WL appears to offer the safest position for the placement of the osteotomy hinge when trying to avoid a fracture at the osteotomy site. Cite this article: Bone Joint J 2017;99B10:1313-18. ©2017 The British Editorial Society of Bone & Joint Surgery.
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Multifunctional Deployment Hinges Rigidified by Ultraviolet
NASA Technical Reports Server (NTRS)
Kerslake, Thomas W.; Simburger, Edward J.; Matusmoto, James; Giants, Thomas W.; Garcia, Alexander; Perry, Alan; Rawal, Suraj; Marshall, Craig; Lin, John Kun Hung; Day, Jonathan Robert;
2005-01-01
Multifunctional hinges have been developed for deploying and electrically connecting panels comprising planar arrays of thin-film solar photovoltaic cells. In the original intended application of these hinges, the panels would be facets of a 32-sided (and approximately spherical) polyhedral microsatellite (see figure), denoted a PowerSphere, that would be delivered to orbit in a compact folded configuration, then deployed by expansion of gas in inflation bladders. Once deployment was complete, the hinges would be rigidified to provide structural connections that would hold the panels in their assigned relative positions without backlash. Such hinges could also be used on Earth for electrically connecting and structurally supporting solar panels that are similarly shipped in compact form and deployed at their destinations. As shown in section A-A in the figure, a hinge of this type is partly integrated with an inflation bladder and partly integrated with the frame of a solar panel. During assembly of the hinge, strip extensions from a flexible circuit harness on the bladder are connected to corresponding thin-film conductors on the solar panel by use of laser welding and wrap-around contacts. The main structural component of the hinge is a layer of glass fiber impregnated with an ultraviolet-curable resin. After deployment, exposure to ultraviolet light from the Sun cures the resin, thereby rigidifying the hinge.
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Shi, Ze; Castro, Carlos E; Arya, Gaurav
2017-05-23
Structural DNA nanotechnology, the assembly of rigid 3D structures of complex yet precise geometries, has recently been used to design dynamic, mechanically compliant nanostructures with tunable equilibrium conformations and conformational distributions. Here we use coarse-grained molecular dynamics simulations to provide insights into the conformational dynamics of a set of mechanically compliant DNA nanostructures-DNA hinges that use single-stranded DNA "springs" to tune the equilibrium conformation of a layered double-stranded DNA "joint" connecting two stiff "arms" constructed from DNA helix bundles. The simulations reproduce the experimentally measured equilibrium angles between hinge arms for a range of hinge designs. The hinges are found to be structurally stable, except for some fraying of the open ends of the DNA helices comprising the hinge arms and some loss of base-pairing interactions in the joint regions coinciding with the crossover junctions, especially in hinges designed to exhibit a small bending angle that exhibit large local stresses resulting in strong kinks in their joints. Principal component analysis reveals that while the hinge dynamics are dominated by bending motion, some twisting and sliding of hinge arms relative to each other also exists. Forced deformation of the hinges reveals distinct bending mechanisms for hinges with short, inextensible springs versus those with longer, more extensible springs. Lastly, we introduce an approach for rapidly predicting equilibrium hinge angles from individual force-deformation behaviors of its single- and double-stranded DNA components. Taken together, these results demonstrate that coarse-grained modeling is a promising approach for designing, predicting, and studying the dynamics of compliant DNA nanostructures, where conformational fluctuations become important, multiple deformation mechanisms exist, and continuum approaches may not yield accurate properties.
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Characterization of flexure hinges for the French watt balance experiment
NASA Astrophysics Data System (ADS)
Pinot, Patrick; Genevès, Gérard
2014-08-01
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.
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Quiroz-Valenzuela, 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 CO2 and nickel ions to gain access to the nascent active site. PMID:18823937
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Tripartite ATP-independent periplasmic (TRAP) transporters in bacteria and archaea.
Mulligan, Christopher; Fischer, Marcus; Thomas, Gavin H
2011-01-01
The tripartite ATP-independent periplasmic (TRAP) transporters are the best-studied family of substrate-binding protein (SBP)-dependent secondary transporters and are ubiquitous in prokaryotes, but absent from eukaryotes. They are comprised of an SBP of the DctP or TAXI families and two integral membrane proteins of unequal sizes that form the DctQ and DctM protein families, respectively. The SBP component has a structure comprised of two domains connected by a hinge that closes upon substrate binding. In DctP-TRAP transporters, substrate binding is mediated through a conserved and specific arginine/carboxylate interaction in the SBP. While the SBP component has now been relatively well characterized, the membrane components of TRAP transporters are still poorly understood both in terms of their structure and function. We review the expanding repertoire of substrates and physiological roles for experimentally characterized TRAP transporters in bacteria and discuss mechanistic aspects of these transporters using data primarily from the sialic acid-specific TRAP transporter SiaPQM from Haemophilus influenzae, which suggest that TRAP transporters are high-affinity, Na(+)-dependent unidirectional secondary transporters. © 2010 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.
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Controlling Flexible Robot Arms Using High Speed Dynamics Process
NASA Technical Reports Server (NTRS)
Jain, Abhinandan (Inventor)
1996-01-01
A robot manipulator controller for a flexible manipulator arm having plural bodies connected at respective movable hinges and flexible in plural deformation modes corresponding to respective modal spatial influence vectors relating deformations of plural spaced nodes of respective bodies to the plural deformation modes, operates by computing articulated body quantities for each of the bodies from respective modal spatial influence vectors, obtaining specified body forces for each of the bodies, and computing modal deformation accelerations of the nodes and hinge accelerations of the hinges from the specified body forces, from the articulated body quantities and from the modal spatial influence vectors. In one embodiment of the invention, the controller further operates by comparing the accelerations thus computed to desired manipulator motion to determine a motion discrepancy, and correcting the specified body forces so as to reduce the motion discrepancy. The manipulator bodies and hinges are characterized by respective vectors of deformation and hinge configuration variables, and computing modal deformation accelerations and hinge accelerations is carried out for each one of the bodies beginning with the outermost body by computing a residual body force from a residual body force of a previous body and from the vector of deformation and hinge configuration variables, computing a resultant hinge acceleration from the body force, the residual body force and the articulated hinge inertia, and revising the residual body force modal body acceleration.
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Controlling flexible robot arms using a high speed dynamics process
NASA Technical Reports Server (NTRS)
Jain, Abhinandan (Inventor); Rodriguez, Guillermo (Inventor)
1992-01-01
Described here is a robot controller for a flexible manipulator arm having plural bodies connected at respective movable hinges, and flexible in plural deformation modes. It is operated by computing articulated body qualities for each of the bodies from the respective modal spatial influence vectors, obtaining specified body forces for each of the bodies, and computing modal deformation accelerations of the nodes and hinge accelerations of the hinges from the specified body forces, from the articulated body quantities and from the modal spatial influence vectors. In one embodiment of the invention, the controller further operates by comparing the accelerations thus computed to desired manipulator motion to determine a motion discrepancy, and correcting the specified body forces so as to reduce the motion discrepancy. The manipulator bodies and hinges are characterized by respective vectors of deformation and hinge configuration variables. Computing modal deformation accelerations and hinge accelerations is carried out for each of the bodies, beginning with the outermost body by computing a residual body force from a residual body force of a previous body, computing a resultant hinge acceleration from the body force, and then, for each one of the bodies beginning with the innermost body, computing a modal body acceleration from a modal body acceleration of a previous body, computing a modal deformation acceleration and hinge acceleration from the resulting hinge acceleration and from the modal body acceleration.
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NASA Technical Reports Server (NTRS)
Wesselski, Clarence J. (Inventor)
1988-01-01
The space station configuration currently studied utilizes structures which require struts to be hinged in the middle in the stowed mode and locked into place in the deployed mode. Since there are hundreds of hinges involved, it is necessary that they have simple, positive locking features with a minimum of joint looseness or slack. This invention comprises two similar housings hinged together with a spring loaded locking member which assists in making as well as breaking the lock. This invention comprises a bracket hinge and bracket members with a spring biased and movable locking member. The locking or latch member has ear parts received in locking openings where wedging surfaces on the ear parts cooperate with complimentary surfaces on the bracket members for bringing the bracket members into a tight end-to-end alignment when the bracket members are in an extended position. When the locking member is moved to an unlocking position, pivoting of the hinge about a pivot pin automatically places the locking member to retain the locking member in an unlocked position. In pivoting the hinge from an extended position to a folded position, longitudinal spring members are placed under tension over annular rollers so that the spring tension in a folded position assists in return of the hinge from a folded to an extended position. Novelty lies in the creation of a locking hinge which allows compact storage and easy assembly of structural members having a minimal number of parts.
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Deployment Testing of Flexible Composite Hinges in Bi-Material Beams
NASA Technical Reports Server (NTRS)
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 deployment repeatability. Also, an interesting creep effect was discovered, that a hinges deployment error would decrease with time.
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Horynová, Milada; Takahashi, Kazuo; Hall, Stacy; Renfrow, Matthew B; Novak, Jan; Raška, Milan
2012-02-01
The human UDP-N-acetyl-α-d-galactosamine:polypeptide N-acetylgalactosaminyl-transferase 2 (GalNAc-T2) is one of the key enzymes that initiate synthesis of hinge-region O-linked glycans of human immunoglobulin A1 (IgA1). We designed secreted soluble form of human GalNAc-T2 as a fusion protein containing mouse immunoglobulin light chain kappa secretory signal and expressed it using baculovirus and mammalian expression vectors. The recombinant protein was secreted by insect cells Sf9 and human HEK 293T cells in the culture medium. The protein was purified from the media using affinity Ni-NTA chromatography followed by stabilization of purified protein in 50mM Tris-HCl buffer at pH 7.4. Although the purity of recombinant GalNAc-T2 was comparable in both expression systems, the yield was higher in Sf9 insect expression system (2.5mg of GalNAc-T2 protein per 1L culture medium). The purified soluble recombinant GalNAc-T2 had an estimated molecular mass of 65.8kDa and its amino-acid sequence was confirmed by mass-spectrometric analysis. The enzymatic activity of Sf9-produced recombinant GalNAc-T2 was determined by the quantification of enzyme-mediated attachment of GalNAc to synthetic IgA1 hinge-region peptide as the acceptor and UDP-GalNAc as the donor. In conclusion, murine immunoglobulin kappa secretory signal was used for production of secreted enzymatically active GalNAc-T2 in insect baculovirus expression system. Copyright © 2011 Elsevier Inc. All rights reserved.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Aggarwal, Megha; Leser, George P.; Kors, Christopher A.
Parainfluenza virus 5 (PIV5) belongs to the familyParamyxoviridae, which consists of enveloped viruses with a nonsegmented negative-strand RNA genome encapsidated by the nucleoprotein (N). Paramyxovirus replication is regulated by the phosphoprotein (P) through protein-protein interactions with N and the RNA polymerase (L). The chaperone activity of P is essential to maintain the unassembled RNA-free form of N in order to prevent nonspecific RNA binding and premature N oligomerization. Here, we determined the crystal structure of unassembled PIV5 N in complex with a P peptide (N 0P) derived from the N terminus of P (P50) at 2.65 Å. The PIV5 Nmore » 0P consists of two domains: an N-terminal domain (NTD) and a C-terminal domain (CTD) separated by a hinge region. The cleft at the hinge region of RNA-bound PIV5 N was previously shown to be an RNA binding site. The N 0P structure shows that the P peptide binds to the CTD of N and extends toward the RNA binding site to inhibit N oligomerization and, hence, RNA binding. Binding of P peptide also keeps the PIV5 N in the open form. A molecular dynamics (MD) analysis of both the open and closed forms of N shows the flexibility of the CTD and the preference of the N protein to be in an open conformation. The gradual opening of the hinge region, to release the RNA, was also observed. Together, these results advance our knowledge of the conformational swapping of N required for the highly regulated paramyxovirus replication. IMPORTANCEParamyxovirus replication is regulated by the interaction of P with N and L proteins. Here, we report the crystal structure of unassembled parainfluenza virus 5 (PIV5) N chaperoned with P peptide. Our results provide a detailed understanding of the binding of P to N. The conformational switching of N between closed and open forms during its initial interaction with P, as well as during RNA release, was analyzed. Our data also show the plasticity of the CTD and the importance of domain movement for conformational switching. The results improve our understanding of the mechanism of interchanging N conformations for RNA replication and release.« less
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Aggarwal, Megha; Leser, George P; Kors, Christopher A; Lamb, Robert A
2018-03-01
Parainfluenza virus 5 (PIV5) belongs to the family Paramyxoviridae , which consists of enveloped viruses with a nonsegmented negative-strand RNA genome encapsidated by the nucleoprotein (N). Paramyxovirus replication is regulated by the phosphoprotein (P) through protein-protein interactions with N and the RNA polymerase (L). The chaperone activity of P is essential to maintain the unassembled RNA-free form of N in order to prevent nonspecific RNA binding and premature N oligomerization. Here, we determined the crystal structure of unassembled PIV5 N in complex with a P peptide (N 0 P) derived from the N terminus of P (P50) at 2.65 Å. The PIV5 N 0 P consists of two domains: an N-terminal domain (NTD) and a C-terminal domain (CTD) separated by a hinge region. The cleft at the hinge region of RNA-bound PIV5 N was previously shown to be an RNA binding site. The N 0 P structure shows that the P peptide binds to the CTD of N and extends toward the RNA binding site to inhibit N oligomerization and, hence, RNA binding. Binding of P peptide also keeps the PIV5 N in the open form. A molecular dynamics (MD) analysis of both the open and closed forms of N shows the flexibility of the CTD and the preference of the N protein to be in an open conformation. The gradual opening of the hinge region, to release the RNA, was also observed. Together, these results advance our knowledge of the conformational swapping of N required for the highly regulated paramyxovirus replication. IMPORTANCE Paramyxovirus replication is regulated by the interaction of P with N and L proteins. Here, we report the crystal structure of unassembled parainfluenza virus 5 (PIV5) N chaperoned with P peptide. Our results provide a detailed understanding of the binding of P to N. The conformational switching of N between closed and open forms during its initial interaction with P, as well as during RNA release, was analyzed. Our data also show the plasticity of the CTD and the importance of domain movement for conformational switching. The results improve our understanding of the mechanism of interchanging N conformations for RNA replication and release. Copyright © 2018 American Society for Microbiology.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
McGinnis, J.P.; Karner, G.D.; Driscoll, N.W.
The tectonic and stratigraphic development of the Congo continental margin reflects the timing, magnitude, and distribution of lithospheric extension responsible for its formation. Details of the lithospheric extension process are recorded in the stratigraphic successions preserved along and across the margin. By using the stratal relationships (e.g., onlap, downlap, and truncation) and lithofacies determined from seismic reflection and exploratory well data as input into our basin-modeling strategy, we have developed an integrated approach to determine the relationship between the timing, magnitude, and distribution of lithospheric extension across the margin. Two hinge zones, an eastern and Atlantic hinge formed along themore » Congo margin in response to discrete extensional events occurring from the Berriasian to the Aptian. The eastern hinge zone demarcates the eastern limit of the broadly distributed Berriasian extension. This extension resulted in the formation of deep anoxic, lacustrine systems. In contrast, the Atlantic hinge, located [approximately]90 km west of the eastern hinge, marks the eastern limit of a second phase of extension, which began in the Hauterivian. Consequent footwall uplift and rotation exposed the earlier synrift and prerift stratigraphy to at least wave base causing varying amounts of erosional truncation across the Atlantic hinge zone along much of the Gabon, Congo, and Angola margins. The absence of the Melania Formation across the Congo margin implies that uplift of the Atlantic hinge was relatively minor compared to that across the Angola and Gabon margins. In addition, material eroded from the adjacent and topographically higher hinge zones may in part account for the thick wedge of sediment deposited seaward of the Congo Atlantic hinge. A third phase of extension reactivated both the eastern and Atlantic hinge zones and was responsible for creating the accommodation space for Marnes Noires source rock deposition.« less
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Ahmed, Mumdooh A M; Bamm, Vladimir V; Harauz, George; Ladizhansky, Vladimir
2007-08-28
The genes of the oligodendrocyte lineage (Golli) encode a family of developmentally regulated isoforms of myelin basic protein. The "classic" MBP isoforms arise from transcription start site 3, whereas Golli-specific isoforms arise from transcription start site 1, and comprise both Golli-specific and classic MBP sequences. The Golli isoform BG21 has been suggested to play roles in myelination and T cell activation pathways. It is an intrinsically disordered protein, thereby presenting a large effective surface area for interaction with other proteins such as Golli-interacting protein. We have used multidimensional heteronuclear NMR spectroscopy to achieve sequence-specific resonance assignments of the recombinant murine BG21 in physiologically relevant buffer, to analyze its secondary structure using chemical shift indexing (CSI), and to investigate its backbone dynamics using 15N spin relaxation measurements. We have assigned 184 out of 199 residues unambiguously. The CSI analysis revealed little ordered secondary structure under these conditions, with only some small fragments having a slight tendency toward alpha-helicity, which may represent putative recognition motifs. The 15N relaxation and NOE measurements confirmed the general behavior of the protein as an extended polypeptide chain, with the N-terminal Golli-specific portion (residues S5-T69) being exceptionally flexible, even in comparison to other intrinsically disordered proteins that have been studied this way. The high degree of flexibility of this N-terminal region may be to provide additional plasticity, or conformational adaptability, in protein-protein interactions. Another highly mobile segment, A126-S127-G128-G129, may function as a hinge.
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Computational Modeling of Shape Memory Polymer Origami that Responds to Light
NASA Astrophysics Data System (ADS)
Mailen, Russell William
Shape memory polymers (SMPs) transform in response to external stimuli, such as infrared (IR) light. Although SMPs have many applications, this investigation focuses on their use as actuators in self-folding origami structures. Ink patterned on the surface of the SMP sheet absorbs thermal energy from the IR light, which produces localized heating. The material shrinks wherever the activation temperature is exceeded and can produce out-of-plane deformation. The time and temperature dependent response of these SMPs provides unique opportunities for developing complex three-dimensional (3D) structures from initially flat sheets through self-folding origami, but the application of this technique requires predicting accurately the final folded or deformed shape. Furthermore, current computational approaches for SMPs do not fully couple the thermo-mechanical response of the material. Hence, a proposed nonlinear, 3D, thermo-viscoelastic finite element framework was formulated to predict deformed shapes for different self-folding systems and compared to experimental results for self-folding origami structures. A detailed understanding of the shape memory response and the effect of controllable design parameters, such as the ink pattern, pre-strain conditions, and applied thermal and mechanical fields, allows for a predictive understanding and design of functional, 3D structures. The proposed modeling framework was used to obtain a fundamental understanding of the thermo-mechanical behavior of SMPs and the impact of the material behavior on hinged self-folding. These predictions indicated how the thermal and mechanical conditions during pre-strain significantly affect the shrinking and folding response of the SMP. Additionally, the externally applied thermal loads significantly influenced the folding rate and maximum bending angle. The computational framework was also adapted to understand the effects of fully coupling the thermal and mechanical response of the material. This updated framework accounted for external heat sources, such as ambient temperature and incident surface heat flux, as well as internal temperature changes due to conduction and viscous heat generation. Viscous heating during the pre-strain sequence affected the residual stresses after cooling due to accelerated viscoelastic relaxation. This resulted in a delayed shrinking and folding response. Other factors that affected the folding response include sheet thickness, hinge width, degree of pre-strain, and hinge temperature. The predicted results indicated that the maximum bending angle can be increased for a folded structure by increasing the hinge width, degree of pre-strain, and hinge surface temperature. Folding time can be reduced by decreasing the sheet thickness, increasing the hinge width, and increasing the hinge temperature. The coupled thermo-mechanical approach was also extended to investigate both curved and folded structures by varying the ink pattern and the substrate geometry. With this approach, two continuous curvature mechanisms were obtained. One was an indirect curvature mechanism which resulted from internal stresses that evolved from the shrinking of activated regions of the material relative to unactivated regions. The second was a direct curvature mechanism that resulted from ink distributed in gradients across the surface of the material. Furthermore, the effects of hinge orientation, proximity of multiple hinges, sheet aspect ratio, and axisymmetric ink patterns were characterized for other shapes, such as rectangles and discs. The findings of this investigation clearly indicate that this validated computational approach can be used to predict and understand the myriad mechanisms of self-folding origami structures. By varying the location of ink on the polymer surface and making changes to the substrate geometry, complex 3D structures can be obtained. The developed thermo-mechanical framework can be used to design optimized origami structures for biomedical devices, space telescopes, and functional, engineered origami devices.
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Cancer prevention, the need to preserve the integrity of the genome at all cost.
Okafor, M T; Nwagha, T U; Anusiem, C; Okoli, U A; Nubila, N I; Al-Alloosh, F; Udenyia, I J
2018-05-01
The entire genetic information carried by an organism makes up its genome. Genes have a diverse number of functions. They code different proteins for normal proliferation of cells. However, changes in the base sequence of genes affect their protein by-products which act as messengers for normal cellular functions such as proliferation and repairs. Salient processes for maintaining the integrity of the genome are hinged on intricate mechanisms put in place for the evolution to tackle genomic stresses. To discuss how cells sense and repair damage to their deoxyribonucleic acid (DNA) as well as to highlight how defects in the genes involved in DNA repair contribute to cancer development. Methodology: Online searches on the following databases such as Google Scholar, PubMed, Biomed Central, and SciELO were done. Attempt was made to review articles with keywords such as cancer, cell cycle, tumor suppressor genes, and DNA repair. The cell cycle, tumor suppression genes, DNA repair mechanism, as well as their contribution to cancer development, were discussed and reviewed. Knowledge on how cells detect and repair DNA damage through an array of mechanisms should allay our anxiety as regards cancer development. More studies on DNA damage detection and repair processes are important toward a holistic approach to cancer treatment.
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Control surface hinge moment prediction using computational fluid dynamics
NASA Astrophysics Data System (ADS)
Simpson, Christopher David
The following research determines the feasibility of predicting control surface hinge moments using various computational methods. A detailed analysis is conducted using a 2D GA(W)-1 airfoil with a 20% plain flap. Simple hinge moment prediction methods are tested, including empirical Datcom relations and XFOIL. Steady-state and time-accurate turbulent, viscous, Navier-Stokes solutions are computed using Fun3D. Hinge moment coefficients are computed. Mesh construction techniques are discussed. An adjoint-based mesh adaptation case is also evaluated. An NACA 0012 45-degree swept horizontal stabilizer with a 25% elevator is also evaluated using Fun3D. Results are compared with experimental wind-tunnel data obtained from references. Finally, the costs of various solution methods are estimated. Results indicate that while a steady-state Navier-Stokes solution can accurately predict control surface hinge moments for small angles of attack and deflection angles, a time-accurate solution is necessary to accurately predict hinge moments in the presence of flow separation. The ability to capture the unsteady vortex shedding behavior present in moderate to large control surface deflections is found to be critical to hinge moment prediction accuracy. Adjoint-based mesh adaptation is shown to give hinge moment predictions similar to a globally-refined mesh for a steady-state 2D simulation.
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NASA Astrophysics Data System (ADS)
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.
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Measuring Conformational Dynamics of Single Biomolecules Using Nanoscale Electronic Devices
NASA Astrophysics Data System (ADS)
Akhterov, Maxim V.; Choi, Yongki; Sims, Patrick C.; Olsen, Tivoli J.; Gul, O. Tolga; Corso, Brad L.; Weiss, Gregory A.; Collins, Philip G.
2014-03-01
Molecular motion can be a rate-limiting step of enzyme catalysis, but motions are typically too quick to resolve with fluorescent single molecule techniques. Recently, we demonstrated a label-free technique that replaced fluorophores with nano-electronic circuits to monitor protein motions. The solid-state electronic technique used single-walled carbon nanotube (SWNT) transistors to monitor conformational motions of a single molecule of T4 lysozyme while processing its substrate, peptidoglycan. As lysozyme catalyzes the hydrolysis of glycosidic bonds, two protein domains undergo 8 Å hinge bending motion that generates an electronic signal in the SWNT transistor. We describe improvements to the system that have extended our temporal resolution to 2 μs . Electronic recordings at this level of detail directly resolve not just transitions between open and closed conformations but also the durations for those transition events. Statistical analysis of many events determines transition timescales characteristic of enzyme activity and shows a high degree of variability within nominally identical chemical events. The high resolution technique can be readily applied to other complex biomolecules to gain insights into their kinetic parameters and catalytic function.
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Deployment Testing of Flexible Composite Hinges in Bi-Material Beams
NASA Technical Reports Server (NTRS)
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.
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Apparatus Producing an Even Distribution of Strain into Carries
NASA Astrophysics Data System (ADS)
Hrabovský, Leopold
2017-10-01
In many high-rise residential buildings or multi-storey warehouses, machinery, so called lifts, is used for the vertical transportation of people or weights between two or more altitudinally distant places. Carriers used for lifts are steel ropes or sprocket chains, on which a cage or a counterbalance is hinged. Apparatus of all carriers, attached to the hinge of the cage or counterbalance, should be even. This can be made only by hammer hinge. Fixed or springe hinge cannot be a perfect equalizing apparatus. This article describes an apparatus, which allows an even distribution of the strain into lift carriers, which use springe hinge of carrier ropes.
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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.
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2013-01-01
Background The widespread protozoan parasite Toxoplasma gondii interferes with host cell functions by exporting the contents of a unique apical organelle, the rhoptry. Among the mix of secreted proteins are an expanded, lineage-specific family of protein kinases termed rhoptry kinases (ROPKs), several of which have been shown to be key virulence factors, including the pseudokinase ROP5. The extent and details of the diversification of this protein family are poorly understood. Results In this study, we comprehensively catalogued the ROPK family in the genomes of Toxoplasma gondii, Neospora caninum and Eimeria tenella, as well as portions of the unfinished genome of Sarcocystis neurona, and classified the identified genes into 42 distinct subfamilies. We systematically compared the rhoptry kinase protein sequences and structures to each other and to the broader superfamily of eukaryotic protein kinases to study the patterns of diversification and neofunctionalization in the ROPK family and its subfamilies. We identified three ROPK sub-clades of particular interest: those bearing a structurally conserved N-terminal extension to the kinase domain (NTE), an E. tenella-specific expansion, and a basal cluster including ROP35 and BPK1 that we term ROPKL. Structural analysis in light of the solved structures ROP2, ROP5, ROP8 and in comparison to typical eukaryotic protein kinases revealed ROPK-specific conservation patterns in two key regions of the kinase domain, surrounding a ROPK-conserved insert in the kinase hinge region and a disulfide bridge in the kinase substrate-binding lobe. We also examined conservation patterns specific to the NTE-bearing clade. We discuss the possible functional consequences of each. Conclusions Our work sheds light on several important but previously unrecognized features shared among rhoptry kinases, as well as the essential differences between active and degenerate protein kinases. We identify the most distinctive ROPK-specific features conserved across both active kinases and pseudokinases, and discuss these in terms of sequence motifs, evolutionary context, structural impact and potential functional relevance. By characterizing the proteins that enable these parasites to invade the host cell and co-opt its signaling mechanisms, we provide guidance on potential therapeutic targets for the diseases caused by coccidian parasites. PMID:23742205
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The mechanism and high-free-energy transition state of lac repressor–lac operator interaction
Sengupta, Rituparna; Capp, Michael W.; Shkel, Irina A.
2017-01-01
Abstract Significant, otherwise-unavailable information about mechanisms and transition states (TS) of protein folding and binding is obtained from solute effects on rate constants. Here we characterize TS for lac repressor(R)–lac operator(O) binding by analyzing effects of RO-stabilizing and RO-destabilizing solutes on association (ka) and dissociation (kd) rate constants. RO-destabilizing solutes (urea, KCl) reduce ka comparably (urea) or more than (KCl) they increase kd, demonstrating that they destabilize TS relative to reactants and RO, and that TS exhibits most of the Coulombic interactions between R and O. Strikingly, three solutes which stabilize RO by favoring burial/dehydration of amide oxygens and anionic phosphate oxygens all reduce kd without affecting ka significantly. The lack of stabilization of TS by these solutes indicates that O phosphates remain hydrated in TS and that TS preferentially buries aromatic carbons and amide nitrogens while leaving amide oxygens exposed. In our proposed mechanism, DNA-binding-domains (DBD) of R insert in major grooves of O pre-TS, forming most Coulombic interactions of RO and burying aromatic carbons. Nucleation of hinge helices creates TS, burying sidechain amide nitrogens. Post-TS, hinge helices assemble and the DBD-hinge helix-O-DNA module docks on core repressor, partially dehydrating phosphate oxygens and tightening all interfaces to form RO. PMID:29036376
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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.
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Hinge-deleted IgG4 blocker therapy for acetylcholine receptor myasthenia gravis in rhesus monkeys.
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.
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Device serves as hinge and electrical connector for circuit boards
NASA Technical Reports Server (NTRS)
Bethel, P. G.; Harris, G. G.
1966-01-01
Hinge makes both sides of electrical circuit boards readily accessible for component checkout and servicing. The hinge permits mounting of two circuit boards and incorporates connectors to maintain continuous electrical contact between the components on both boards.
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Hinge Moment Coefficient Prediction Tool and Control Force Analysis of Extra-300 Aerobatic Aircraft
NASA Astrophysics Data System (ADS)
Nurohman, Chandra; Arifianto, Ony; Barecasco, Agra
2018-04-01
This paper presents the development of tool that is applicable to predict hinge moment coefficients of subsonic aircraft based on Roskam’s method, including the validation and its application to predict hinge moment coefficient of an Extra-300. The hinge moment coefficients are used to predict the stick forces of the aircraft during several aerobatic maneuver i.e. inside loop, half cuban 8, split-s, and aileron roll. The maximum longitudinal stick force is 566.97 N occurs in inside loop while the maximum lateral stick force is 340.82 N occurs in aileron roll. Furthermore, validation hinge moment prediction method is performed using Cessna 172 data.
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NASA Technical Reports Server (NTRS)
Bachmann, M.; Shiraishi, N.; Campbell, W. H.; Yoo, B. C.; Harmon, A. C.; Huber, S. C.; Davies, E. (Principal Investigator)
1996-01-01
Spinach leaf NADH:nitrate reductase (NR) responds to light/dark signals and photosynthetic activity in part as a result of rapid regulation by reversible protein phosphorylation. We have identified the major regulatory phosphorylation site as Ser-543, which is located in the hinge 1 region connecting the cytochrome b domain with the molybdenum-pterin cofactor binding domain of NR, using recombinant NR fragments containing or lacking the phosphorylation site sequence. Studies with NR partial reactions indicated that the block in electron flow caused by phosphorylation also could be localized to the hinge 1 region. A synthetic peptide (NR6) based on the phosphorylation site sequence was phosphorylated readily by NR kinase (NRk) in vitro. NR6 kinase activity tracked the ATP-dependent inactivation of NR during several chromatographic steps and completely inhibited inactivation/phosphorylation of native NR in vitro. Two forms of NRk were resolved by using anion exchange chromatography. Studies with synthetic peptide analogs indicated that both forms of NRk had similar specificity determinants, requiring a basic residue at P-3 (i.e., three amino acids N-terminal to the phosphorylated serine) and a hydrophobic residue at P-5. Both forms are strictly calcium dependent but belong to distinct families of protein kinases because they are distinct immunochemically.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Quiroz, Soledad; Sukuru, Sai Chetan K.; Hausinger, Robert P.
2008-01-01
Conformational changes of Klebsiella aerogenes urease apoprotein (UreABC){sub 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 complexmore » that includes all of the accessory proteins. SAXS analyses of urease, (UreABC-UreD){sub 3}, and (UreABC-UreDF){sub 3} confirm that UreD and UreF bind near UreB at the periphery of the (UreAC){sub 3} structure. This study supports an activation model in which a domain-shifted UreB conformation in (UreABC-UreDF){sub 3} allows CO{sub 2} and nickel ions to gain access to the nascent active site.« less
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Dungan, C F; Elston, R A; Schiewe, M H
1989-01-01
Several strains of cytophaga-like gliding bacteria (CLB) were isolated as numerically dominant or codominant components of bacterial populations associated with proteinaceous hinge ligaments of cultured juvenile Pacific oysters, Crassostrea gigas. These bacteria were morphologically similar to long, flexible bacilli occurring within degenerative lesions in oyster hinge ligaments. Among bacteria isolated from hinge ligaments, only CLB strains were capable of sustained growth with hinge ligament matrix as the sole source of organic carbon and nitrogen. In vitro incubation of cuboidal portions of ligament resilium with ligament CLB resulted in bacterial proliferation on the surfaces and penetration deep into ligament matrices. Bacterial proliferation was accompanied by loss of resilium structural and mechanical integrity, including complete liquefaction, at incubation temperatures between 10 and 20 degrees C. The morphological, distributional, and degradative characteristics of CLB isolated from oyster hinge ligaments provide compelling, albeit indirect, evidence that CLB are the agents of a degenerative disease affecting juvenile cultured oysters. The motility, metabolic, and hydrolytic characteristics of hinge ligament CLB and the low moles percent G + C values (32.4 to 32.9) determined for three representative strains indicate that they are marine Cytophaga spp. Images PMID:2757377
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Dungan, C F; Elston, R A; Schiewe, M H
1989-05-01
Several strains of cytophaga-like gliding bacteria (CLB) were isolated as numerically dominant or codominant components of bacterial populations associated with proteinaceous hinge ligaments of cultured juvenile Pacific oysters, Crassostrea gigas. These bacteria were morphologically similar to long, flexible bacilli occurring within degenerative lesions in oyster hinge ligaments. Among bacteria isolated from hinge ligaments, only CLB strains were capable of sustained growth with hinge ligament matrix as the sole source of organic carbon and nitrogen. In vitro incubation of cuboidal portions of ligament resilium with ligament CLB resulted in bacterial proliferation on the surfaces and penetration deep into ligament matrices. Bacterial proliferation was accompanied by loss of resilium structural and mechanical integrity, including complete liquefaction, at incubation temperatures between 10 and 20 degrees C. The morphological, distributional, and degradative characteristics of CLB isolated from oyster hinge ligaments provide compelling, albeit indirect, evidence that CLB are the agents of a degenerative disease affecting juvenile cultured oysters. The motility, metabolic, and hydrolytic characteristics of hinge ligament CLB and the low moles percent G + C values (32.4 to 32.9) determined for three representative strains indicate that they are marine Cytophaga spp.
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Impact buckling of thin bars in the elastic range hinged at both ends
NASA Technical Reports Server (NTRS)
Koning, Carel; Taub, Josef
1934-01-01
Following the development of the well-known differential equations of the problem and their resolution for failure in tension, the bending (transverse) oscillations of an originally not quite straight bar hinged at both ends and subjected to a constant longitudinal force (shock load) are analyzed. To this end the course of the bar form is expanded in a sinusoidal series, after which the investigation is carried through separately for the fundamental oscillation and the (n-1)the higher oscillations. The analysis of the fundamental oscillation distinguishes three cases: shock load lower, equal to, or higher than the Eulerian load. The investigation leads to functions which are proportional to the maximum stresses in time and space due to the shock stresses in buckling.
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Explicit frequency equations of free vibration of a nonlocal Timoshenko beam with surface effects
NASA Astrophysics Data System (ADS)
Zhao, Hai-Sheng; Zhang, Yao; Lie, Seng-Tjhen
2018-02-01
Considerations of nonlocal elasticity and surface effects in micro- and nanoscale beams are both important for the accurate prediction of natural frequency. In this study, the governing equation of a nonlocal Timoshenko beam with surface effects is established by taking into account three types of boundary conditions: hinged-hinged, clamped-clamped and clamped-hinged ends. For a hinged-hinged beam, an exact and explicit natural frequency equation is obtained. However, for clamped-clamped and clamped-hinged beams, the solutions of corresponding frequency equations must be determined numerically due to their transcendental nature. Hence, the Fredholm integral equation approach coupled with a curve fitting method is employed to derive the approximate fundamental frequency equations, which can predict the frequency values with high accuracy. In short, explicit frequency equations of the Timoshenko beam for three types of boundary conditions are proposed to exhibit directly the dependence of the natural frequency on the nonlocal elasticity, surface elasticity, residual surface stress, shear deformation and rotatory inertia, avoiding the complicated numerical computation.
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Parametric analysis and temperature effect of deployable hinged shells using shape memory polymers
NASA Astrophysics Data System (ADS)
Tao, Ran; Yang, Qing-Sheng; He, Xiao-Qiao; Liew, Kim-Meow
2016-11-01
Shape memory polymers (SMPs) are a class of intelligent materials, which are defined by their capacity to store a temporary shape and recover an original shape. In this work, the shape memory effect of SMP deployable hinged shell is simulated by using compiled user defined material subroutine (UMAT) subroutine of ABAQUS. Variations of bending moment and strain energy of the hinged shells with different temperatures and structural parameters in the loading process are given. The effects of the parameters and temperature on the nonlinear deformation process are emphasized. The entire thermodynamic cycle of SMP deployable hinged shell includes loading at high temperature, load carrying with cooling, unloading at low temperature and recovering the original shape with heating. The results show that the complicated thermo-mechanical deformation and shape memory effect of SMP deployable hinge are influenced by the structural parameters and temperature. The design ability of SMP smart hinged structures in practical application is prospected.
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Real-Time Flight Envelope Monitoring System
NASA Technical Reports Server (NTRS)
Kerho, Michael; Bragg, Michael B.; Ansell, Phillip J.
2012-01-01
The objective of this effort was to show that real-time aircraft control-surface hinge-moment information could be used to provide a robust and reliable prediction of vehicle performance and control authority degradation. For a given airfoil section with a control surface -- be it a wing with an aileron, rudder, or elevator -- the control-surface hinge moment is sensitive to the aerodynamic characteristics of the section. As a result, changes in the aerodynamics of the section due to angle-of-attack or environmental effects such as icing, heavy rain, surface contaminants, bird strikes, or battle damage will affect the control surface hinge moment. These changes include both the magnitude of the hinge moment and its sign in a time-averaged sense, and the variation of the hinge moment with time. The current program attempts to take the real-time hinge moment information from the aircraft control surfaces and develop a system to predict aircraft envelope boundaries across a range of conditions, alerting the flight crew to reductions in aircraft controllability and flight boundaries.
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NASA Astrophysics Data System (ADS)
Axen, Gary J.; Bartley, John M.; Selverstone, Jane
1995-12-01
The kinematic and temporal sequence of structures observed to overprint mylonites along the Brenner Line low-angle normal fault may record passage of the footwall through two rolling hinges, at the top and bottom of a ramp in the shear zone. The structures comprise west down brittle and brittle-ductile structures and east down brittle structures. PT conditions of formation (250° to >400°C and 2-23 km depth), obtained from analysis of oriented fluid inclusion planes, indicate that west down structures were formed at greater depths and temperatures, and therefore earlier, than the east down structures. These data suggest that the brittle structures formed under conditions that permit crystal-plastic deformation at long-term geologic strain rates and therefore probably reflect transient rapid strain rates and/or high fluid pressure. Structures inferred to have formed at a lower hinge are consistent with viscous flow models of rolling-hinge deformation and support the concept of a crustal asthenosphere. Such high temperatures at shallow crustal depth also suggest significant upward advection of heat by extensional unroofing of warm rocks, which may have reduced the flexural rigidity of the footwall and thus affected mechanical behavior at the upper rolling hinge. Exposed mylonitic foliation within a few hundred meters of the Brenner line and on top of the east-west trending anticlines in the footwall dips ˜15° west. Our data favor a ramp dip of ˜25° but permit a dip as great as 45°. Fluid inclusion data suggest that structures related to the hinge at the base of the ramp formed at depths of 12-25 km. If the average dip of the Brenner shear zone to those depths was 20°, intermediate between the favored ramp dip and the dip of exposed foliation, then the horizontal component of slip could be as high as 33-63 km. The two discrete sets of structures with opposite shear senses, formed in the temporal sequence indicated by PT data, are consistent with subvertical simple shear models of rolling-hinge strain. This kinematic pattern is not predicted by the flexural-failure model for rolling hinges. However, the predominance of normal slip at the upper hinge, which extends rather than shortens the mylonitic foliation, fails to match the subvertical simple shear model, which predicts shortening of the foliation there. One possible solution is that superposition of regional extension upon hinge-related stresses modified the rolling-hinge kinematics. Such a modified subvertical shear model can account for the observed small foliation-parallel extensional strains if the foliation was bent <5°-10° passing through the upper hinge. If more bending than that occurred, the data suggest rolling-hinge kinematics in which deformation is achieved by uniform-sense simple shear across the shear zone as in the subvertical simple shear model but in which material lines parallel to the shear-zone foliation and the detachment fault undergo very small length changes, presumably indicating that footwall rocks retained significant resistance to shear and underwent minimal permanent strain. The mechanics that would generate such a rolling hinge are uncertain but may incorporate aspects of both subvertical simple shear and flexural failure. An important kinematic consequence of such a rolling hinge is that all of the net slip across a normal fault, not only its horizontal component, is converted into horizontal extension. This implies a significantly larger magnitude of crustal extension across dipping normal faults whose footwalls passed through a rolling hinge than for those that did not develop along with a hinge.
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Dragon, François; Pogačić, Vanda; Filipowicz, Witold
2000-01-01
The H/ACA small nucleolar RNAs (snoRNAs) are involved in pseudouridylation of pre-rRNAs. They usually fold into a two-domain hairpin-hinge-hairpin-tail structure, with the conserved motifs H and ACA located in the hinge and tail, respectively. Synthetic RNA transcripts and extracts from HeLa cells were used to reconstitute human U17 and other H/ACA ribonucleoproteins (RNPs) in vitro. Competition and UV cross-linking experiments showed that proteins of about 60, 29, 23, and 14 kDa interact specifically with U17 RNA. Except for U17, RNPs could be reconstituted only with full-length H/ACA snoRNAs. For U17, the 3′-terminal stem-loop followed by box ACA (U17/3′st) was sufficient to form an RNP, and U17/3′st could compete other full-length H/ACA snoRNAs for assembly. The H/ACA-like domain that constitutes the 3′ moiety of human telomerase RNA (hTR), and its 3′-terminal stem-loop (hTR/3′st), also could form an RNP by binding H/ACA proteins. Hence, the 3′-terminal stem-loops of U17 and hTR have some specific features that distinguish them from other H/ACA RNAs. Antibodies that specifically recognize the human GAR1 (hGAR1) protein could immunoprecipitate H/ACA snoRNAs and hTR from HeLa cell extracts, which demonstrates that hGAR1 is a component of H/ACA snoRNPs and telomerase in vivo. Moreover, we show that in vitro-reconstituted RNPs contain hGAR1 and that binding of hGAR1 does not appear to be a prerequisite for the assembly of the other H/ACA proteins. PMID:10757788
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Epididymal secreted protein Crisp-1 and sperm function.
Roberts, Kenneth P; Ensrud, Kathy M; Wooters, Joseph L; Nolan, Michael A; Johnston, Daniel S; Hamilton, David W
2006-05-16
Crisp-1 is a member of the cysteine-rich secretory protein family. This family of proteins is characterized by the presence of 16 conserved cysteine residues, the characteristic from which the family name is derived. Members of the Crisp protein family are found in the secretions of the reproductive tract and salivary glands, including venom toxins from several species of snakes and lizards. The Crisp proteins are modular, each containing an amino terminal pathogenesis-related (PR)-like domain and a carboxyl terminal cysteine-rich domain (CRD) connected by a hinge region. Sequence and structural similarities to proteins with known functions suggest that the Crisp family of proteins may act by regulating cellular ion channels. Rat Crisp-1 is synthesized as two distinct isoforms (referred to as Proteins D and E) by the epididymal epithelium and both are secreted into the luminal fluid where they interact with spermatozoa. Our laboratory has correlated Crisp-1 binding to sperm with inhibiting the signaling cascades that initiate capacitation while others have shown that blocking Crisp-1 binding sites on oocytes interferes with sperm-egg fusion. We hypothesize that the D and E populations of rat Crisp-1 have different interactions with sperm that modulate these distinct biological activities. Through tandem mass spectrometry (MS/MS) and monosaccharide composition analyses, we have identified at least one difference between the D and E forms as an additional single O-linked N-acetyl galactosamine on an amino terminal threonine residue in Protein E. This post-translational modification appears to account for the unique 'E' epitope bound by monoclonal antibody 4E9 developed in our laboratory, and may also lead to differential processing and localization of Protein E on sperm, when compared to Protein D. These findings are the first step in distinguishing the molecular basis of the biological activities of the D and E forms of rat Crisp-1. The epididymal-specific expression of Crisp-1, combined with its role in regulation of sperm capacitation and oocyte interaction, make it an attractive target for post-testicular contraceptive development.
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Designing Great Hinge Questions
ERIC Educational Resources Information Center
Wiliam, Dylan
2015-01-01
According to author Dylan Wiliam, because lessons never go exactly as planned, teachers should build plan B into plan A. This involves designing a lesson with a "hinge" somewhere in the middle and using specific kinds of questions--what he calls hinge questions--to quickly assess students' understanding of a concept before moving on.…
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A Self-Categorization Explanation for Opinion Consensus Perceptions
ERIC Educational Resources Information Center
Zhang, Jinguang; Reid, Scott A.
2013-01-01
The public expression of opinions (and related communicative activities) hinges upon the perception of opinion consensus. Current explanations for opinion consensus perceptions typically focus on egocentric and other biases, rather than functional cognitions. Using self-categorization theory we showed that opinion consensus perceptions flow from…
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Deployable Soft Composite Structures.
Wang, Wei; Rodrigue, Hugo; Ahn, Sung-Hoon
2016-02-19
Deployable structure composed of smart materials based actuators can reconcile its inherently conflicting requirements of low mass, good shape adaptability, and high load-bearing capability. This work describes the fabrication of deployable structures using smart soft composite actuators combining a soft matrix with variable stiffness properties and hinge-like movement through a rigid skeleton. The hinge actuator has the advantage of being simple to fabricate, inexpensive, lightweight and simple to actuate. This basic actuator can then be used to form modules capable of different types of deformations, which can then be assembled into deployable structures. The design of deployable structures is based on three principles: design of basic hinge actuators, assembly of modules and assembly of modules into large-scale deployable structures. Various deployable structures such as a segmented triangular mast, a planar structure comprised of single-loop hexagonal modules and a ring structure comprised of single-loop quadrilateral modules were designed and fabricated to verify this approach. Finally, a prototype for a deployable mirror was developed by attaching a foldable reflective membrane to the designed ring structure and its functionality was tested by using it to reflect sunlight onto to a small-scale solar panel.
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Deployable Soft Composite Structures
Wang, Wei; Rodrigue, Hugo; Ahn, Sung-Hoon
2016-01-01
Deployable structure composed of smart materials based actuators can reconcile its inherently conflicting requirements of low mass, good shape adaptability, and high load-bearing capability. This work describes the fabrication of deployable structures using smart soft composite actuators combining a soft matrix with variable stiffness properties and hinge-like movement through a rigid skeleton. The hinge actuator has the advantage of being simple to fabricate, inexpensive, lightweight and simple to actuate. This basic actuator can then be used to form modules capable of different types of deformations, which can then be assembled into deployable structures. The design of deployable structures is based on three principles: design of basic hinge actuators, assembly of modules and assembly of modules into large-scale deployable structures. Various deployable structures such as a segmented triangular mast, a planar structure comprised of single-loop hexagonal modules and a ring structure comprised of single-loop quadrilateral modules were designed and fabricated to verify this approach. Finally, a prototype for a deployable mirror was developed by attaching a foldable reflective membrane to the designed ring structure and its functionality was tested by using it to reflect sunlight onto to a small-scale solar panel. PMID:26892762
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Bezabeh, Binyam; Fleming, Ryan; Fazenbaker, Christine; Zhong, Haihong; Coffman, Karen; Yu, Xiang-Qing; Leow, Ching Ching; Gibson, Nerea; Wilson, Susan; Stover, C Kendall; Wu, Herren; Gao, Changshou; Dimasi, Nazzareno
By simultaneous binding two disease mediators, bispecific antibodies offer the opportunity to broaden the utility of antibody-based therapies. Herein, we describe the design and characterization of Bs4Ab, an innovative and generic bispecific tetravalent antibody platform. The Bs4Ab format comprises a full-length IgG1 monoclonal antibody with a scFv inserted into the hinge domain. The Bs4Ab design demonstrates robust manufacturability as evidenced by MEDI3902, which is currently in clinical development. To further demonstrate the applicability of the Bs4Ab technology, we describe the molecular engineering, biochemical, biophysical, and in vivo characterization of a bispecific tetravalent Bs4Ab that, by simultaneously binding vascular endothelial growth factor and angiopoietin-2, inhibits their function. We also demonstrate that the Bs4Ab platform allows Fc-engineering similar to that achieved with IgG1 antibodies, such as mutations to extend half-life or modulate effector functions.
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Gervois, P; Torra, I P; Chinetti, G; Grötzinger, T; Dubois, G; Fruchart, J C; Fruchart-Najib, J; Leitersdorf, E; Staels, B
1999-09-01
The peroxisome proliferator-activated receptor alpha (PPARalpha) plays a key role in lipid and lipoprotein metabolism. However, important inter- and intraspecies differences exist in the response to PPARalpha activators. This incited us to screen for PPARalpha variants with different signaling functions. In the present study, using a RT-PCR approach a variant human PPARalpha mRNA species was identified, which lacks the entire exon 6 due to alternative splicing. This deletion leads to the introduction of a premature stop codon, resulting in the formation of a truncated PPARalpha protein (PPARalphatr) lacking part of the hinge region and the entire ligand-binding domain. RNase protection analysis demonstrated that PPARalphatr mRNA is expressed in several human tissues and cells, representing between 20-50% of total PPARalpha mRNA. By contrast, PPARalphatr mRNA could not be detected in rodent tissues. Western blot analysis using PPARalpha-specific antibodies demonstrated the presence of an immunoreactive protein migrating at the size of in vitro produced PPARalphatr protein both in human hepatoma HepG2 cells and in human hepatocytes. Both in the presence or absence of 9-cis-retinoic acid receptor, PPARalphatr did not bind to DNA in gel shift assays. Immunocytochemical analysis of transfected CV-1 cells indicated that, whereas transfected PPARalphawt was mainly nuclear localized, the majority of PPARalphatr resided in the cytoplasm, with presence in the nucleus depending on cell culture conditions. Whereas a chimeric PPARalphatr protein containing a nuclear localization signal cloned at its N-terminal localized into the nucleus and exhibited strong negative activity on PPARalphawt transactivation function, PPARalphatr interfered with PPARalphatr transactivation function only under culture conditions inducing its nuclear localization. Cotransfection of the coactivator CREB-binding protein relieved the transcriptional repression of PPARalphawt by PPARalphatr, suggesting that the dominant negative effect of PPARalphatr might occur through competition for essential coactivators. In addition, PPARalphatr interfered with transcriptional activity of other nuclear receptors such as PPARgamma, hepatic nuclear factor-4, and glucocorticoid receptor-alpha, which share CREB-binding protein/p300 as a coactivator. Thus, we have identified a human PPARalpha splice variant that may negatively interfere with PPARalphawt function. Factors regulating either the ratio of PPARalphawt vs. PPARalphatr mRNA or the nuclear entry of PPARalphatr protein should therefore lead to altered signaling via the PPARalpha and, possibly also, other nuclear receptor pathways.
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Non-equivalent role of TM2 gating hinges in heteromeric Kir4.1/Kir5.1 potassium channels.
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.
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NASA Technical Reports Server (NTRS)
Rignot, Eric
1997-01-01
Satellite synthetic-aperture radar (SAR) Interferometry is employed to map the hinge line, or limit of tidal flexing, of Rutford Ice Stream and Carlson Inlet, Antarctica, and detect its migration between 1992 and 1996. The hinge line is mapped using a model fit from an elastic beam theory.
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77 FR 49396 - Airworthiness Directives; The Boeing Company Airplanes
Federal Register 2010, 2011, 2012, 2013, 2014
2012-08-16
... option for installing a redesigned aft hinge fitting with the trim already done, instead of trimming an... installing a redesigned aft hinge fitting with the trim already done, instead of trimming an existing or new... action in the existing AD) for installing a redesigned aft hinge fitting designed with the trim already...
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78 FR 33197 - Airworthiness Directives; Iniziative Industriali Italiane S.p.A. Airplanes
Federal Register 2010, 2011, 2012, 2013, 2014
2013-06-04
... plane hinge assembly. We are issuing this AD to require actions to address the unsafe condition on these... plane hinge assembly have been reported. This condition, if not detected and corrected, could lead to... bearing and the horizontal tail/elevator plane hinge assembly to detect any crack, signs of corrosion or...
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Fc-fusion Proteins in Therapy: An Updated View.
Jafari, Reza; Zolbanin, Naime M; Rafatpanah, Houshang; Majidi, Jafar; Kazemi, Tohid
2017-01-01
Fc-fusion proteins are composed of Fc region of IgG antibody (Hinge-CH2-CH3) and a desired linked protein. Fc region of Fc-fusion proteins can bind to neonatal Fc receptor (FcRn) thereby rescuing it from degradation. The first therapeutic Fc-fusion protein was introduced for the treatment of AIDS. The molecular designing is the first stage in production of Fc-fusion proteins. The amino acid residues in the Fc region and linked protein are very important in the bioactivity and affinity of the fusion proteins. Although, therapeutic monoclonal antibodies are the top selling biologics but the application of therapeutic Fc-fusion proteins in clinic is in progress and among these medications Etanercept is the most effective in therapy. At present, eleven Fc-fusion proteins have been approved by FDA. There are novel Fc-fusion proteins which are in pre-clinical and clinical development. In this article, we review the molecular and biological characteristics of Fc-fusion proteins and then further discuss the features of novel therapeutic Fc-fusion proteins. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
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NASA Technical Reports Server (NTRS)
Fleischer, G. E.; Likins, P. W.
1975-01-01
Three computer subroutines designed to solve the vector-dyadic differential equations of rotational motion for systems that may be idealized as a collection of hinge-connected rigid bodies assembled in a tree topology, with an optional flexible appendage attached to each body are reported. Deformations of the appendages are mathematically represented by modal coordinates and are assumed small. Within these constraints, the subroutines provide equation solutions for (1) the most general case of unrestricted hinge rotations, with appendage base bodies nominally rotating at a constant speed, (2) the case of unrestricted hinge rotations between rigid bodies, with the restriction that those rigid bodies carrying appendages are nominally nonspinning, and (3) the case of small hinge rotations and nominally nonrotating appendages. Sample problems and their solutions are presented to illustrate the utility of the computer programs.
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Structural insights into the multifunctional protein VP3 of birnaviruses.
Casañas, Arnau; Navarro, Aitor; Ferrer-Orta, Cristina; González, Dolores; Rodríguez, José F; Verdaguer, Núria
2008-01-01
Infectious bursal disease virus (IBDV), a member of the Birnaviridae family, is the causative agent of one of the most harmful poultry diseases. The IBDV genome encodes five mature proteins; of these, the multifunctional protein VP3 plays an essential role in virus morphogenesis. This protein, which interacts with the structural protein VP2, with the double-stranded RNA genome, and with the virus-encoded, RNA-dependent RNA polymerase, VP1, is involved not only in the formation of the viral capsid, but also in the recruitment of VP1 into the capsid and in the encapsidation of the viral genome. Here, we report the X-ray structure of the central region of VP3, residues 92-220, consisting of two alpha-helical domains connected by a long and flexible hinge that are organized as a dimer. Unexpectedly, the overall fold of the second VP3 domain shows significant structural similarities with different transcription regulation factors.
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Design and 4D Printing of Cross-Folded Origami Structures: A Preliminary Investigation.
Teoh, Joanne Ee Mei; An, Jia; Feng, Xiaofan; Zhao, Yue; Chua, Chee Kai; Liu, Yong
2018-03-03
In 4D printing research, different types of complex structure folding and unfolding have been investigated. However, research on cross-folding of origami structures (defined as a folding structure with at least two overlapping folds) has not been reported. This research focuses on the investigation of cross-folding structures using multi-material components along different axes and different horizontal hinge thickness with single homogeneous material. Tensile tests were conducted to determine the impact of multi-material components and horizontal hinge thickness. In the case of multi-material structures, the hybrid material composition has a significant impact on the overall maximum strain and Young's modulus properties. In the case of single material structures, the shape recovery speed is inversely proportional to the horizontal hinge thickness, while the flexural or bending strength is proportional to the horizontal hinge thickness. A hinge with a thickness of 0.5 mm could be folded three times prior to fracture whilst a hinge with a thickness of 0.3 mm could be folded only once prior to fracture. A hinge with a thickness of 0.1 mm could not even be folded without cracking. The introduction of a physical hole in the center of the folding/unfolding line provided stress relief and prevented fracture. A complex flower petal shape was used to successfully demonstrate the implementation of overlapping and non-overlapping folding lines using both single material segments and multi-material segments. Design guidelines for establishing cross-folding structures using multi-material components along different axes and different horizontal hinge thicknesses with single or homogeneous material were established. These guidelines can be used to design and implement complex origami structures with overlapping and non-overlapping folding lines. Combined overlapping folding structures could be implemented and allocating specific hole locations in the overall designs could be further explored. In addition, creating a more precise prediction by investigating sets of in between hinge thicknesses and comparing the folding times before fracture, will be the subject of future work.
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Federal Register 2010, 2011, 2012, 2013, 2014
2011-03-10
..., an operator found an aileron trim tab hinge pin that had migrated sufficiently to cause a rubbing.... Recently, during a walk round check, an operator found an aileron trim tab hinge pin that had migrated... walk round check, an operator found an aileron trim tab hinge pin that had migrated sufficiently to...
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Window Operator Types | Efficient Windows Collaborative
Types Casement Casement Casement windows are hinged at the sides. Hinged windows such as casements operating types to consider. Traditional operable window types include the projected or hinged types such as casement, awning, and hopper, and the sliding types such as double- and single-hung and horizontal sliding
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Serfling, Robert; Lorenz, Christian; Etzel, Maja; Schicht, Gerda; Böttke, Thore; Mörl, Mario
2018-01-01
Abstract The pyrrolysyl-tRNA synthetase/tRNAPyl pair is the most versatile and widespread system for the incorporation of non-canonical amino acids (ncAAs) into proteins in mammalian cells. However, low yields of ncAA incorporation severely limit its applicability to relevant biological targets. Here, we generate two tRNAPyl variants that significantly boost the performance of the pyrrolysine system. Compared to the original tRNAPyl, the engineered tRNAs feature a canonical hinge between D- and T-loop, show higher intracellular concentrations and bear partially distinct post-transcriptional modifications. Using the new tRNAs, we demonstrate efficient ncAA incorporation into a G-protein coupled receptor (GPCR) and simultaneous ncAA incorporation at two GPCR sites. Moreover, by incorporating last-generation ncAAs for bioorthogonal chemistry, we achieve GPCR labeling with small organic fluorophores on the live cell and visualize stimulus-induced GPCR internalization. Such a robust system for incorporation of single or multiple ncAAs will facilitate the application of a wide pool of chemical tools for structural and functional studies of challenging biological targets in live mammalian cells. PMID:29177436
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Borowska-Wykret, Dorota; Rypien, Aleksandra; Dulski, Mateusz; Grelowski, Michal; Wrzalik, Roman; Kwiatkowska, Dorota
2017-06-01
The capitulum of Helichrysum bracteatum is surrounded by scarious involucral bracts that perform hygroscopic movements leading to bract bending toward or away from the capitulum, depending on cell wall water status. The present investigation aimed at explaining the mechanism of these movements. Surface strain and bract shape changes accompanying the movements were quantified using the replica method. Dissection experiments were used to assess the contribution of different tissues in bract deformation. Cell wall structure and composition were examined with the aid of light and electron microscopy as well as confocal Raman spectroscopy. At the bract hinge (organ actuator) longitudinal strains at opposite surfaces differ profoundly. This results in changes of hinge curvature that drive passive displacement of distal bract portions. The distal portions in turn undergo nearly uniform strain on both surfaces and also minute shape changes. The hinge is built of sclerenchyma-like abaxial tissue, parenchyma and adaxial epidermis with thickened outer walls. Cell wall composition is rather uniform but tissue fraction occupied by cell walls, cell wall thickness, compactness and cellulose microfibril orientation change gradually from abaxial to adaxial hinge surface. Dissection experiments show that the presence of part of the hinge tissues is enough for movements. Differential strain at the hinge is due to adaxial-abaxial gradient in structural traits of hinge tissues and cell walls. Thus, the bract hinge of H. bracteatum is a structure comprising gradually changing tissues, from highly resisting to highly active, rather than a bi-layered structure with distinct active and resistance parts, often ascribed for hygroscopically moving organs. © The Author 2017. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com
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Lee, Wei-Shiun; Linz, Shang-Chih; Shih, Kao-Shang; Chao, Ching-Kong; Chen, Yeung-Jen; Fan, Chang-Yuan
2012-10-01
Stiffness and contracture of the periarticular tissues are common complications of a post-traumatic elbow. Arthrodiatasis is a surgical technique that uses an external fixator for initial immobilization and subsequent distraction. The two prerequisites for an ideal arthrodiatasis are concentric distraction (avoiding bony contact) and hinge alignment (reducing internal stress). This study used the finite element (FE) method to clarify the relationship between these two prerequisites and the initial conditions (pin placement, elbow angle, and distraction mode). A total of 12 variations of the initial conditions were symmetrically arranged to evaluate their biomechanical influence on concentric distraction and hinge alignment. The humeroulnar surface was hypothesized to be ideally distracted orthogonal to the line joining the tips of the olecranon and the coronoid. The eccentric separation of the humeroulnar surfaces is a response to the non-orthogonality of the distracting force and joining line. Pin placement significantly affects the effective moment arm of the fixing pins to distract the bridged elbow. Both elbow angle and distraction mode directly alter the direction of the distracting force at the elbow center. In general, the hinges misalignment occurs in a direction opposite to the distraction-activated site. After joint distraction, the elastic deflection of the fixing pins inevitably makes both elbow and fixator hinges to misalign. This indicates that both joint distraction and hinge alignment are the interactive mechanisms. The humeroulnar separation is more concentric in the situation of the 120 degrees humeral distraction by using stiffer pins with convergent placement. Even so, the eccentric displacement of the elbow hinge is a crucial consideration in the initial placement of the guiding pin to compensate for hinge misalignment.
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The role of hinges in primary total knee replacement.
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.
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Analysis of intelligent hinged shell structures: deployable deformation and shape memory effect
NASA Astrophysics Data System (ADS)
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.
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Custom rotating hinge total knee arthroplasty in patients with poliomyelitis affected limbs.
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 < 0.001). The rotating hinge (SMILES) prosthesis is effective at relieving pain and improving function in patients with poliomyelitis. The device compensates well for ligamentous insufficiency as well as for any associated bony deformity.
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NASA Technical Reports Server (NTRS)
Schoen, A. H. (Inventor)
1973-01-01
Expandable space frames having essentially infinite periodicity limited only by practical considerations, are described. Each expandable space frame comprises a plurality of hinge joint assemblies having arms that extend outwardly in predetermined symmetrically related directions from a central or vertex point. The outer ends of the arms form one part of a hinge point. The outer expandable space frame also comprises a plurality of struts. The outer ends of the struts from the other part of the hinged joint. The struts interconnect the plurality of hinge point in sychronism, the spaceframes can be expanded or collapsed. Three-dimensional as well as two-dimensional spaceframes of this general nature are described.
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Graphite Composite Booms with Integral Hinges
NASA Technical Reports Server (NTRS)
Alexander, Wes; Carlos, Rene; Rossoni, Peter; Sturm, James
2006-01-01
A document discusses lightweight instrument booms under development for use aboard spacecraft. A boom of this type comprises a thin-walled graphite fiber/ matrix composite tube with an integral hinge that can be bent for stowage and later allowed to spring back to straighten the boom for deployment in outer space. The boom design takes advantage of both the stiffness of the composite in tubular geometry and the flexibility of thin sections of the composite. The hinge is formed by machining windows in the tube at diametrically opposite locations so that there remain two opposing cylindrical strips resembling measuring tapes. Essential to the design is a proprietary composite layup that renders the hinge tough yet flexible enough to be bendable as much as 90 in either of two opposite directions. When the boom is released for deployment, the torque exerted by the bent hinge suffices to overcome parasitic resistance from harnesses and other equipment, so that the two sections of the hinge snap to a straight, rigid condition in the same manner as that of measuring tapes. Issues addressed in development thus far include selection of materials, out-of-plane bending, edge cracking, and separation of plies.
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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 < 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. PMID:27203597
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Chauhan, Aakash; Palmer, Bradley A; Baratz, Mark E
2015-06-01
Total elbow arthroplasty is successful in older, lower demand patients but not in the younger, more active individual with severe elbow arthritis. Interposition arthroplasty is an alternative for younger patients who hope to minimize the degree to which arm use is restricted. Interposition arthroplasty traditionally involves release of all ligaments and capsule. As a result, the postoperative care included the use of a hinged external fixator of the elbow to apply distraction and to permit motion during the early phases of healing. We describe a novel surgical technique without a hinged external fixator that allows secure fixation of the interposition graft through arthroscopic assistance and maintains the integrity of the medial collateral ligament with only a takedown and repair of the lateral collateral ligament complex. A retrospective chart review was performed to analyze 4 patients with an average age of 57 years who underwent surgery between 2007 and 2011. The patients were also contacted to assess elbow-specific American Shoulder and Elbow Surgeons and Disabilities of the Arm, Shoulder, and Hand scores. The average follow-up was 3.6 years (range, 2.5-6 years), and 1 patient was converted to a total elbow arthroplasty after 2.5 years because of persistent pain. The remaining 3 patients have done well with regard to pain control, stability, and functional use of the operative extremity. There were no postoperative complications. On the basis of our small series of patients, an arthroscopically assisted elbow interposition arthroplasty without hinged external fixation can provide satisfactory medium-term outcomes as a salvage procedure for a difficult condition with limited options. Copyright © 2015 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.
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NASA Astrophysics Data System (ADS)
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.
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Curvature estimation for multilayer hinged structures with initial strains
NASA Astrophysics Data System (ADS)
Nikishkov, G. P.
2003-10-01
Closed-form estimate of curvature for hinged multilayer structures with initial strains is developed. The finite element method is used for modeling of self-positioning microstructures. The geometrically nonlinear problem with large rotations and large displacements is solved using step procedure with node coordinate update. Finite element results for curvature of the hinged micromirror with variable width is compared to closed-form estimates.
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Design and 4D Printing of Cross-Folded Origami Structures: A Preliminary Investigation
Teoh, Joanne Ee Mei; Feng, Xiaofan; Zhao, Yue; Liu, Yong
2018-01-01
In 4D printing research, different types of complex structure folding and unfolding have been investigated. However, research on cross-folding of origami structures (defined as a folding structure with at least two overlapping folds) has not been reported. This research focuses on the investigation of cross-folding structures using multi-material components along different axes and different horizontal hinge thickness with single homogeneous material. Tensile tests were conducted to determine the impact of multi-material components and horizontal hinge thickness. In the case of multi-material structures, the hybrid material composition has a significant impact on the overall maximum strain and Young’s modulus properties. In the case of single material structures, the shape recovery speed is inversely proportional to the horizontal hinge thickness, while the flexural or bending strength is proportional to the horizontal hinge thickness. A hinge with a thickness of 0.5 mm could be folded three times prior to fracture whilst a hinge with a thickness of 0.3 mm could be folded only once prior to fracture. A hinge with a thickness of 0.1 mm could not even be folded without cracking. The introduction of a physical hole in the center of the folding/unfolding line provided stress relief and prevented fracture. A complex flower petal shape was used to successfully demonstrate the implementation of overlapping and non-overlapping folding lines using both single material segments and multi-material segments. Design guidelines for establishing cross-folding structures using multi-material components along different axes and different horizontal hinge thicknesses with single or homogeneous material were established. These guidelines can be used to design and implement complex origami structures with overlapping and non-overlapping folding lines. Combined overlapping folding structures could be implemented and allocating specific hole locations in the overall designs could be further explored. In addition, creating a more precise prediction by investigating sets of in between hinge thicknesses and comparing the folding times before fracture, will be the subject of future work. PMID:29510503
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Beckstein, Oliver; Denning, Elizabeth J.; Perilla, Juan R.; Woolf, Thomas B.
2009-01-01
Adenylate kinase (AdK), a phosphotransferase enzyme, plays an important role in cellular energy homeostasis. It undergoes a large conformational change between an open and a closed state, even in the absence of substrate. We investigate the apo-AdK transition at the atomic level both with free energy calculations and our new dynamic importance sampling (DIMS) molecular dynamics (MD) method. DIMS is shown to sample biologically relevant conformations as verified by comparing an ensemble of hundreds of DIMS transitions to AdK crystal structure intermediates. The simulations reveal in atomic detail how hinge regions partially and intermittently unfold during the transition. Conserved salt bridges are seen to have important structural and dynamic roles; in particular four ionic bonds are identified that open in a sequential, zipper-like fashion and thus dominate the free energy landscape of the transition. Transitions between the closed and open conformations only have to overcome moderate free energy barriers. Unexpectedly, the closed and open state encompass broad free energy basins that contain conformations differing in domain hinge motions by up to 40°. The significance of these extended states is discussed in relation to recent experimental FRET measurements. Taken together, these results demonstrate how a small number of cooperative key interactions can shape the overall dynamics of an enzyme and suggest an “all-or-nothing” mechanism for the opening and closing of AdK. Our efficient DIMS-MD computer simulation approach can provide a detailed picture of a functionally important macromolecular transition and thus help to interpret and suggest experiments to probe the conformational landscape of dynamic proteins such as AdK. PMID:19751742
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Xing, Li; Shieh, Huey S.; Selness, Shaun R.
2009-07-24
PH-797804 is a diarylpyridinone inhibitor of p38{alpha} mitogen-activated protein (MAP) kinase derived from a racemic mixture as the more potent atropisomer (aS), first proposed by molecular modeling and subsequently confirmed by experiments. On the basis of structural comparison with a different biaryl pyrazole template and supported by dozens of high-resolution crystal structures of p38{alpha} inhibitor complexes, PH-797804 is predicted to possess a high level of specificity across the broad human kinase genome. We used a structural bioinformatics approach to identify two selectivity elements encoded by the TXXXG sequence motif on the p38{alpha} kinase hinge: (i) Thr106 that serves as themore » gatekeeper to the buried hydrophobic pocket occupied by 2,4-difluorophenyl of PH-797804 and (ii) the bidentate hydrogen bonds formed by the pyridinone moiety with the kinase hinge requiring an induced 180{sup o} rotation of the Met109-Gly110 peptide bond. The peptide flip occurs in p38{alpha} kinase due to the critical glycine residue marked by its conformational flexibility. Kinome-wide sequence mining revealed rare presentation of the selectivity motif. Corroboratively, PH-797804 exhibited exceptionally high specificity against MAP kinases and the related kinases. No cross-reactivity was observed in large panels of kinase screens (selectivity ratio of >500-fold). In cellular assays, PH-797804 demonstrated superior potency and selectivity consistent with the biochemical measurements. PH-797804 has met safety criteria in human phase I studies and is under clinical development for several inflammatory conditions. Understanding the rationale for selectivity at the molecular level helps elucidate the biological function and design of specific p38{alpha} kinase inhibitors.« less
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One Stage Conversion of an Infected Fused Knee to Total Knee Replacement - A Surgical Challenge
Ravikumar, Mukartihal; Kendoff, Daniel; Citak, Mustafa; Luck, Stefan; Gehrke, Thorsten; Zahar, Akos
2013-01-01
Background and Purpose: Two-stage revision arthroplasty is a common technique for the treatment of infected total knee replacement. Few reports have addressed the conversion of a fused knee into a total knee replacement. However, there is no case reported of converting an infected fused knee into a hinge knee using a one-stage procedure. Methods: We report on a 51-year old male patient with an infected fused knee after multiple surgeries. Results and Interpretation: A one-stage conversion of septic fused knee into total knee arthroplasty by a rotational hinge prosthesis was performed. The case highlights that with profound preoperative assessment, meticulous surgical technique, combined antibiotic treatment and the right implant, one-stage revision in a surgical challenge may have a role as a treatment option with good functional outcome. PMID:23526706
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Ahn, Yu Mi; Clare, Michael; Ensinger, Carol L.
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 themore » doubly phosphorylated form of p38-alpha kinase.« less
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Vandergriff, D.H.
1999-08-31
A hinge assembly is disclosed having a first leaf, a second leaf and linking member. The first leaf has a contact surface. The second leaf has a first contact surface and a second contact surface. The linking member pivotally connects to the first leaf and to the second leaf. The hinge assembly is capable of moving from a closed position to an open position. In the closed position, the contact surface of the first leaf merges with the first contact surface of the second leaf. In the open position, the contact surface of the first leaf merges with the second contact surface of the second leaf. The hinge assembly can include a seal on the contact surface of the first leaf. 8 figs.
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Vandergriff, David Houston
1999-01-01
A hinge assembly having a first leaf, a second leaf and linking member. The first leaf has a contact surface. The second leaf has a first contact surface and a second contact surface. The linking member pivotally connects to the first leaf and to the second leaf. The hinge assembly is capable of moving from a closed position to an open position. In the closed position, the contact surface of the first leaf merges with the first contact surface of the second leaf. In the open position, the contact surface of the first leaf merges with the second contact surface of the second leaf. The hinge assembly can include a seal on the contact surface of the first leaf.
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Wang, Zhihui; Cheng, Ke; Wan, Liyun; Yan, Liying; Jiang, Huifang; Liu, Shengyi; Lei, Yong; Liao, Boshou
2015-12-10
Plant bZIP proteins characteristically harbor a highly conserved bZIP domain with two structural features: a DNA-binding basic region and a leucine (Leu) zipper dimerization region. They have been shown to be diverse transcriptional regulators, playing crucial roles in plant development, physiological processes, and biotic/abiotic stress responses. Despite the availability of six completely sequenced legume genomes, a comprehensive investigation of bZIP family members in legumes has yet to be presented. In this study, we identified 428 bZIP genes encoding 585 distinct proteins in six legumes, Glycine max, Medicago truncatula, Phaseolus vulgaris, Cicer arietinum, Cajanus cajan, and Lotus japonicus. The legume bZIP genes were categorized into 11 groups according to their phylogenetic relationships with genes from Arabidopsis. Four kinds of intron patterns (a-d) within the basic and hinge regions were defined and additional conserved motifs were identified, both presenting high group specificity and supporting the group classification. We predicted the DNA-binding patterns and the dimerization properties, based on the characteristic features in the basic and hinge regions and the Leu zipper, respectively, which indicated that some highly conserved amino acid residues existed across each major group. The chromosome distribution and analysis for WGD-derived duplicated blocks revealed that the legume bZIP genes have expanded mainly by segmental duplication rather than tandem duplication. Expression data further revealed that the legume bZIP genes were expressed constitutively or in an organ-specific, development-dependent manner playing roles in multiple seed developmental stages and tissues. We also detected several key legume bZIP genes involved in drought- and salt-responses by comparing fold changes of expression values in drought-stressed or salt-stressed roots and leaves. In summary, this genome-wide identification, characterization and expression analysis of legume bZIP genes provides valuable information for understanding the molecular functions and evolution of the legume bZIP transcription factor family, and highlights potential legume bZIP genes involved in regulating tissue development and abiotic stress responses.
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Liang, Wenguang G.; Ren, Min; Zhao, Fan; ...
2015-01-27
CC chemokine ligands (CCL) are 8-14 kDa signaling proteins involved in diverse immune functions. While CCLs share similar tertiary structures, oligomerization produces highly diverse quaternary structures that protect chemokines from proteolytic degradation and modulate their functions. CCL18 is closely related to CCL3 and CCL4 with respect to both protein sequence and genomic location, yet CCL18 has distinct biochemical and biophysical properties. Here in this paper, we report a crystal structure of human CCL18 and its oligomerization states in solution based on crystallographic and small angle X-ray scattering (SAXS) analyses. Our data shows that CCL18 adopts an α-helical conformation at itsmore » N-terminus that weakens its dimerization, explaining CCL18’s preference for the monomeric state. Multiple contacts between monomers allow CCL18 to reversibly form a unique open-ended oligomer different from those of CCL3, CCL4, and CCL5. Furthermore, these differences hinge on proline 8, which is conserved in CCL3 and CCL4, but is replaced by lysine in human CCL18. Our structural analyses suggest that a proline 8 to alanine mutation stabilizes a type I β-turn at the N-terminus of CCL4 to prevent dimerization but prevents dimers from making key contacts with each other in CCL3. Thus, the P8A mutation induces depolymerization of CCL3 and CCL4 by distinct mechanisms. Finally, we used structural, biochemical, and functional analyses to unravel why insulin-degrading enzyme (IDE) degrades CCL3 and CCL4 but not CCL18. Lastly, our results elucidate the molecular basis for the oligomerization of three closely related CC chemokines and suggest how oligomerization shapes CCL chemokine function.« less
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Liang, Wenguang G; Ren, Min; Zhao, Fan; Tang, Wei-Jen
2015-03-27
CC chemokine ligands (CCLs) are 8- to 14-kDa signaling proteins involved in diverse immune functions. While CCLs share similar tertiary structures, oligomerization produces highly diverse quaternary structures that protect chemokines from proteolytic degradation and modulate their functions. CCL18 is closely related to CCL3 and CCL4 with respect to both protein sequence and genomic location, yet CCL18 has distinct biochemical and biophysical properties. Here, we report a crystal structure of human CCL18 and its oligomerization states in solution based on crystallographic and small-angle X-ray scattering analyses. Our data show that CCL18 adopts an α-helical conformation at its N-terminus that weakens its dimerization, explaining CCL18's preference for the monomeric state. Multiple contacts between monomers allow CCL18 to reversibly form a unique open-ended oligomer different from those of CCL3, CCL4, and CCL5. Furthermore, these differences hinge on proline 8, which is conserved in CCL3 and CCL4 but is replaced by lysine in human CCL18. Our structural analyses suggest that a mutation of proline 8 to alanine stabilizes a type 1 β-turn at the N-terminus of CCL4 to prevent dimerization but prevents dimers from making key contacts with each other in CCL3. Thus, the P8A mutation induces depolymerization of CCL3 and CCL4 by distinct mechanisms. Finally, we used structural, biochemical, and functional analyses to unravel why insulin-degrading enzyme degrades CCL3 and CCL4 but not CCL18. Our results elucidate the molecular basis for the oligomerization of three closely related CC chemokines and suggest how oligomerization shapes CCL chemokine function. Copyright © 2015 Elsevier Ltd. All rights reserved.
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Blacklock, Kristin; Verkhivker, Gennady M.
2013-01-01
Allosteric interactions of the molecular chaperone Hsp90 with a large cohort of cochaperones and client proteins allow for molecular communication and event coupling in signal transduction networks. The integration of cochaperones into the Hsp90 system is driven by the regulatory mechanisms that modulate the progression of the ATPase cycle and control the recruitment of the Hsp90 clientele. In this work, we report the results of computational modeling of allosteric regulation in the Hsp90 complexes with the cochaperones p23 and Aha1. By integrating protein docking, biophysical simulations, modeling of allosteric communications, protein structure network analysis and the energy landscape theory we have investigated dynamics and stability of the Hsp90-p23 and Hsp90-Aha1 interactions in direct comparison with the extensive body of structural and functional experiments. The results have revealed that functional dynamics and allosteric interactions of Hsp90 can be selectively modulated by these cochaperones via specific targeting of the regulatory hinge regions that could restrict collective motions and stabilize specific chaperone conformations. The protein structure network parameters have quantified the effects of cochaperones on conformational stability of the Hsp90 complexes and identified dynamically stable communities of residues that can contribute to the strengthening of allosteric interactions. According to our results, p23-mediated changes in the Hsp90 interactions may provide “molecular brakes” that could slow down an efficient transmission of the inter-domain allosteric signals, consistent with the functional role of p23 in partially inhibiting the ATPase cycle. Unlike p23, Aha1-mediated acceleration of the Hsp90-ATPase cycle may be achieved via modulation of the equilibrium motions that facilitate allosteric changes favoring a closed dimerized form of Hsp90. The results of our study have shown that Aha1 and p23 can modulate the Hsp90-ATPase activity and direct the chaperone cycle by exerting the precise control over structural stability, global movements and allosteric communications in Hsp90. PMID:23977182
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Language Development Hinges on Communication: An Emergentist Perspective
ERIC Educational Resources Information Center
Abrar-Ul-Hassan, Shahid
2011-01-01
Studies on the human language system have brought to the fore two key aspects. First, the prime function of language is communication. Second, language exists in the social world. The language learning process takes place within the sociocultural context and the relevant macrostructures that influence language use and development. According to the…
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Inelastic seismic response of precast concrete frames with constructed plastic hinges
NASA Astrophysics Data System (ADS)
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.
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Origami-Inspired Folding of Thick, Rigid Panels
NASA Technical Reports Server (NTRS)
Trease, Brian P.; Thomson, Mark W.; Sigel, Deborah A.; Walkemeyer, Phillip E.; Zirbel, Shannon; Howell, Larry; Lang, Robert
2014-01-01
To achieve power of 250 kW or greater, a large compression ratio of stowed-to-deployed area is needed. Origami folding patterns were used to inspire the folding of a solar array to achieve synchronous deployment; however, origami models are generally created for near-zero-thickness material. Panel thickness is one of the main challenges of origami-inspired design. Three origami-inspired folding techniques (flasher, square twist, and map fold) were created with rigid panels and hinges. Hinge components are added to the model to enable folding of thick, rigid materials. Origami models are created assuming zero (or near zero) thickness. When a material with finite thickness is used, the panels are required to bend around an increasingly thick fold as they move away from the center of the model. The two approaches for dealing with material thickness are to use membrane hinges to connect the panels, or to add panel hinges, or hinges of the same thickness, at an appropriate width to enable folding.
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Hinged external fixation of the elbow.
Chen, Neal C; Julka, Abhishek
2010-08-01
Hinged external fixation of the elbow provides the advantages of static fixation with the benefits of continued motion through the joint. Indications for the use of this method of fixation include traumatic instability, distraction interposition arthroplasty, instability after contracture release, and instability after excision of heterotopic ossification. Orthopedic surgeons should be familiar with hinged fixators and their application when faced with an unstable ulnohumeral joint. 2010 Elsevier Inc. All rights reserved.
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Friesenbichler, Joerg; Maurer-Ertl, Werner; Sadoghi, Patrick; Lovse, Thomas; Windhager, Reinhard; Leithner, Andreas
2012-03-01
The effects of systemic metal ion exposure in patients with implants made of common prosthetic alloys continue to be a matter of concern. The aim of the study was to determine the measurement values of cobalt (Co), chromium (Cr) and molybdenum (Mo) in serum following rotating-hinge knee arthroplasty. Blood was taken from 25 patients [mean follow-up 35 (range nine to 67) months] treated with megaprostheses (n=17) or standard rotating-hinge devices (n=8) and analysed using electrothermal graphite furnace atomic absorption spectrometry (ET-ASS). Determining the concentrations of metal ions following rotating-hinge knee arthroplasty revealed increments for Co and Cr but not Mo. Metal ion release was significantly higher in patients with megaprostheses compared to a standard rotating-hinge knee device (Co p=0,024; Cr p=0.025). The authors believe there might be an additional metal ion release from the surface of the prosthesis and not only from the articulating surfaces because, in cases of rotating-hinge knee prosthesis, there is a metal-on-polyethylene articulation and not a direct metal-on-metal junction. Nevertheless, long-term studies are required to determine adverse effects of Co, Cr and Mo following total hip replacement and total knee arthroplasty.
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Genome-Wide Analysis of bZIP-Encoding Genes in Maize
Wei, Kaifa; Chen, Juan; Wang, Yanmei; Chen, Yanhui; Chen, Shaoxiang; Lin, Yina; Pan, Si; Zhong, Xiaojun; Xie, Daoxin
2012-01-01
In plants, basic leucine zipper (bZIP) proteins regulate numerous biological processes such as seed maturation, flower and vascular development, stress signalling and pathogen defence. We have carried out a genome-wide identification and analysis of 125 bZIP genes that exist in the maize genome, encoding 170 distinct bZIP proteins. This family can be divided into 11 groups according to the phylogenetic relationship among the maize bZIP proteins and those in Arabidopsis and rice. Six kinds of intron patterns (a–f) within the basic and hinge regions are defined. The additional conserved motifs have been identified and present the group specificity. Detailed three-dimensional structure analysis has been done to display the sequence conservation and potential distribution of the bZIP domain. Further, we predict the DNA-binding pattern and the dimerization property on the basis of the characteristic features in the basic and hinge regions and the leucine zipper, respectively, which supports our classification greatly and helps to classify 26 distinct subfamilies. The chromosome distribution and the genetic analysis reveal that 58 ZmbZIP genes are located in the segmental duplicate regions in the maize genome, suggesting that the segment chromosomal duplications contribute greatly to the expansion of the maize bZIP family. Across the 60 different developmental stages of 11 organs, three apparent clusters formed represent three kinds of different expression patterns among the ZmbZIP gene family in maize development. A similar but slightly different expression pattern of bZIPs in two inbred lines displays that 22 detected ZmbZIP genes might be involved in drought stress. Thirteen pairs and 143 pairs of ZmbZIP genes show strongly negative and positive correlations in the four distinct fungal infections, respectively, based on the expression profile and Pearson's correlation coefficient analysis. PMID:23103471
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SIMS: A Hybrid Method for Rapid Conformational Analysis
Gipson, Bryant; Moll, Mark; Kavraki, Lydia E.
2013-01-01
Proteins are at the root of many biological functions, often performing complex tasks as the result of large changes in their structure. Describing the exact details of these conformational changes, however, remains a central challenge for computational biology due the enormous computational requirements of the problem. This has engendered the development of a rich variety of useful methods designed to answer specific questions at different levels of spatial, temporal, and energetic resolution. These methods fall largely into two classes: physically accurate, but computationally demanding methods and fast, approximate methods. We introduce here a new hybrid modeling tool, the Structured Intuitive Move Selector (sims), designed to bridge the divide between these two classes, while allowing the benefits of both to be seamlessly integrated into a single framework. This is achieved by applying a modern motion planning algorithm, borrowed from the field of robotics, in tandem with a well-established protein modeling library. sims can combine precise energy calculations with approximate or specialized conformational sampling routines to produce rapid, yet accurate, analysis of the large-scale conformational variability of protein systems. Several key advancements are shown, including the abstract use of generically defined moves (conformational sampling methods) and an expansive probabilistic conformational exploration. We present three example problems that sims is applied to and demonstrate a rapid solution for each. These include the automatic determination of “active” residues for the hinge-based system Cyanovirin-N, exploring conformational changes involving long-range coordinated motion between non-sequential residues in Ribose-Binding Protein, and the rapid discovery of a transient conformational state of Maltose-Binding Protein, previously only determined by Molecular Dynamics. For all cases we provide energetic validations using well-established energy fields, demonstrating this framework as a fast and accurate tool for the analysis of a wide range of protein flexibility problems. PMID:23935893
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Magnetic second-order topological insulators and semimetals
NASA Astrophysics Data System (ADS)
Ezawa, Motohiko
2018-04-01
We propose magnetic second-order topological insulators (SOTIs). First, we study a three-dimensional model. It is pointed out that the previously proposed topological hinge insulator has actually surface states along the [001] direction in addition to hinge states. We gap out these surface states by introducing magnetization, obtaining a SOTI only with hinge states. The bulk topological number is the Z2 index protected by the combined symmetry of the fourfold rotation and the inversion symmetry. We next study two-dimensional magnetic SOTIs, where the corner states are robust also in the presence of the magnetization. Finally, we construct a magnetic second-order topological semimetal by layering the two-dimensional magnetic SOTIs, where hinge-arc states are robust also in the presence of the magnetization.
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Study on Transverse Load Distribution of Hinged Hollow Beam
NASA Astrophysics Data System (ADS)
Wang, Weiyue; Zhang, Chao; Wan, Shui
2017-11-01
The bridge is a kind of space structure, when the car load on a part of the bridge, the impact of its load will be transmitted to the surrounding. In this paper, the hinge plate method is used to calculate and analyze the simply supported hollow slab of a certain arch bridge. Considering the hinge plate mounting method is suitable for pouring concrete bridge connecting the longitudinal tongue and groove joints, horizontal beams fabricated separate beam only in the middle between the free flaps or reinforced with steel connection. Therefore, the transverse analysis and calculation of the superstructure of box girder are carried out by using hinge plate method. And mechanical analysis of the transverse beam with finite element software MIDAS Civil grillage method.
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Functional Characterization of the Vitamin K2 Biosynthetic Enzyme UBIAD1
Hirota, Yoshihisa; Nakagawa, Kimie; Sawada, Natsumi; Okuda, Naoko; Suhara, Yoshitomo; Uchino, Yuri; Kimoto, Takashi; Funahashi, Nobuaki; Kamao, Maya; Tsugawa, Naoko; Okano, Toshio
2015-01-01
UbiA prenyltransferase domain-containing protein 1 (UBIAD1) plays a significant role in vitamin K2 (MK-4) synthesis. We investigated the enzymological properties of UBIAD1 using microsomal fractions from Sf9 cells expressing UBIAD1 by analysing MK-4 biosynthetic activity. With regard to UBIAD1 enzyme reaction conditions, highest MK-4 synthetic activity was demonstrated under basic conditions at a pH between 8.5 and 9.0, with a DTT ≥0.1 mM. In addition, we found that geranyl pyrophosphate and farnesyl pyrophosphate were also recognized as a side-chain source and served as a substrate for prenylation. Furthermore, lipophilic statins were found to directly inhibit the enzymatic activity of UBIAD1. We analysed the aminoacid sequences homologies across the menA and UbiA families to identify conserved structural features of UBIAD1 proteins and focused on four highly conserved domains. We prepared protein mutants deficient in the four conserved domains to evaluate enzyme activity. Because no enzyme activity was detected in the mutants deficient in the UBIAD1 conserved domains, these four domains were considered to play an essential role in enzymatic activity. We also measured enzyme activities using point mutants of the highly conserved aminoacids in these domains to elucidate their respective functions. We found that the conserved domain I is a substrate recognition site that undergoes a structural change after substrate binding. The conserved domain II is a redox domain site containing a CxxC motif. The conserved domain III is a hinge region important as a catalytic site for the UBIAD1 enzyme. The conserved domain IV is a binding site for Mg2+/isoprenyl side-chain. In this study, we provide a molecular mapping of the enzymological properties of UBIAD1. PMID:25874989
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NASA Astrophysics Data System (ADS)
Pavlenko, Olga V.; Pigusov, Evgeny A.
2018-05-01
The paper discusses the approach of numerical simulation of the boundary layer control (BLC) on deflected flap for suppression of flow separation. Computational investigations were carried out using a program based on numerically solving the Reynolds averaged Navier-Stokes equations. The aim of this work is numerical investigation of the aerodynamic loads and hinge moments of the flap with BLC with influence of the walls of the wind tunnel. We have made a calculation of the airfoil section with flap deflected by 20° and 60° with variation of blowing momentum coefficient of Cμ=0÷0.1. The comparison of the calculation results with the experimental values of lift coefficient, pitching moment and pressure coefficient is presented. The pressure distribution on all surface of the wing and the threedimensional flow pattern of the wing with BLC, influence of the walls of the wind tunnel and the aerodynamic loads and hinge moments of the BLC flap are given. It is shown that the 20° flap increases the jet momentum coefficient from Cμ=0 to Cμ=0.1, leads to an increase of the hinge moment coefficient almost in 2 times, and the 60° flap increases the jet momentum coefficient from Cμ=0 to Cμ=0.113, leads to an increase of the hinge moment coefficient almost 3.5 times. The magnitude of the hinge moment on the flap with BLC rises due to the increase of the total aerodynamic force acting on the flap. As a result, the jet blowing on the plain flap leads to the significant increase of the hinge moment that must be considered when designing the high-lift devices with BLC.
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Hirst, Deborah V.L.; Dunn, Kevin H.; Shulman, Stanley A.; Hammond, Duane R.; Sestito, Nicholas
2015-01-01
Exposures to diacetyl, a primary ingredient of butter flavoring, have been shown to cause respiratory disease among workers who mix flavorings. This study focused on evaluating ventilation controls designed to reduce emissions from the flavor mixing tanks, the major source of diacetyl in the plants. Five exhaust hood configurations were evaluated in the laboratory: standard hinged lid-opened, standard hinged lid-closed, hinged lid-slotted, dome with 38-mm gap, and dome with 114-mm gap. Tracer gas tests were performed to evaluate quantitative capture efficiency for each hood. A perforated copper coil was used to simulate an area source within the 1.2-meter diameter mixing tank. Capture efficiencies were measured at four hood exhaust flow rates (2.83, 5.66, 11.3, and 17.0 cubic meters per minute) and three cross draft velocities (0, 30, and 60 meters per minute). All hoods evaluated performed well with capture efficiencies above 90% for most combinations of exhaust volume and cross drafts. The standard hinged lid was the least expensive to manufacture and had the best average capture efficiency (over 99%) in the closed configuration for all exhaust flow rates and cross drafts. The hinged lid-slotted hood had some of the lowest capture efficiencies at the low exhaust flow rates compared to the other hood designs. The standard hinged lid performed well, even in the open position, and it provided a flexible approach to controlling emissions from mixing tanks. The dome hood gave results comparable to the standard hinged lid but it is more expensive to manufacture. The results of the study indicate that emissions from mixing tanks used in the production of flavorings can be controlled using simple inexpensive exhaust hoods. PMID:24649880
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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.
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Kinematics analysis on hinges of robot arm gripper for harmful chemical handling
NASA Astrophysics Data System (ADS)
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.
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Platelet activation through a Bi-leaflet mechanical heart valve
NASA Astrophysics Data System (ADS)
Hedayat, Mohammadali; Borazjani, Iman
2016-11-01
Platelet activation is one of the major drawbacks of the Mechanical Heart Valves (MHVs) which can increase the risk of thrombus formation in patients. The platelet activation in MHVs can be due to the abnormal shear stress during the systole, the backward leakage flow during the diastole, and the flow through the hinge region. We investigate the contribution of each of the above mechanism to the activation of platelets in MHVs by performing simulations of the flow through the MHV and in the hinge region. The large scale heart valve simulations are performed in a straight aorta using a sharp interface curvilinear immersed boundary method along with a strong-coupling algorithm under physiological flow conditions. In addition, in order to perform the simulation of hinge region the flow field boundary conditions are obtained from the largescale simulations during a whole cardiac cycle. In order to investigate the role of hinge flow on platelet activation in MHVs, a 23mm St. Jude Medical Regent valve hinge with three different gap sizes is tested along with different platelet activation models to ensure the consistency of our results with different activation models. We compare the platelet activation of the hinge region against the bulk of the flow during one cardiac cycle. 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.
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ERIC Educational Resources Information Center
AlBzoor, Baseel Ali
2011-01-01
Liyerature;Drawing upon intrinsic linguistic and cultural premises, the present study is an attempt to explore semantic and pragmatic failure, evidently and frequently arising while translating literary texts. This researcher has adopted a functional approach that hinges upon basic semantic and pragmatic premises that best fit the framework of an…
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Hinged Capsulotomy – Does it Decrease Floaters After Yttrium Aluminum Garnet Laser Capsulotomy?
Alipour, Fatemeh; Jabbarvand, Mahmoud; Hashemian, Hesam; Hosseini, Simindokht; Khodaparast, Mehdi
2015-01-01
Objectives: The objective was to compare conventional circular yttrium aluminum garnet (YAG) laser capsulotomy with hinged capsulotomy to manage posterior capsular opacification (PCO). Materials and Methods: This prospective, randomized clinical trial enrolled pseudophakic patients with visually significant posterior capsule opacification. Patients were randomized to undergo posterior YAG laser capsulotomy with either conventional circular technique or a new technique with an inferior hinge. At 1-month postoperatively, patients were asked if they had any annoying floaters and the responses were compared between groups. P < 0.05 was considered statistically significant. Results: A total of 83 patients were enrolled. Forty-three patients underwent hinged posterior YAG capsulotomy and 40 patients underwent routine circular capsulotomy. At 1-month postoperatively, there was a statistically significant decrease in annoying floaters in the group that underwent circular capsulotomy (P = 0.02). There was no statistically significant association in the total energy delivered (P = 0.4) or the number of spots (P = 0.2) and patient perception of annoying floaters. Conclusion: Hinged YAG capsulotomy was effective at decreasing the rate of floaters in patients with PCO. PMID:26180476
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Hinged Capsulotomy--Does it Decrease Floaters After Yttrium Aluminum Garnet Laser Capsulotomy?
Alipour, Fatemeh; Jabbarvand, Mahmoud; Hashemian, Hesam; Hosseini, Simindokht; Khodaparast, Mehdi
2015-01-01
The objective was to compare conventional circular yttrium aluminum garnet (YAG) laser capsulotomy with hinged capsulotomy to manage posterior capsular opacification (PCO). This prospective, randomized clinical trial enrolled pseudophakic patients with visually significant posterior capsule opacification. Patients were randomized to undergo posterior YAG laser capsulotomy with either conventional circular technique or a new technique with an inferior hinge. At 1-month postoperatively, patients were asked if they had any annoying floaters and the responses were compared between groups. P < 0.05 was considered statistically significant. A total of 83 patients were enrolled. Forty-three patients underwent hinged posterior YAG capsulotomy and 40 patients underwent routine circular capsulotomy. At 1-month postoperatively, there was a statistically significant decrease in annoying floaters in the group that underwent circular capsulotomy (P = 0.02). There was no statistically significant association in the total energy delivered (P = 0.4) or the number of spots (P = 0.2) and patient perception of annoying floaters. Hinged YAG capsulotomy was effective at decreasing the rate of floaters in patients with PCO.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Valley, Cary T.; Porter, Douglas F.; Qiu, Chen
2012-06-28
mRNA control hinges on the specificity and affinity of proteins for their RNA binding sites. Regulatory proteins must bind their own sites and reject even closely related noncognate sites. In the PUF [Pumilio and fem-3 binding factor (FBF)] family of RNA binding proteins, individual proteins discriminate differences in the length and sequence of binding sites, allowing each PUF to bind a distinct battery of mRNAs. Here, we show that despite these differences, the pattern of RNA interactions is conserved among PUF proteins: the two ends of the PUF protein make critical contacts with the two ends of the RNA sites.more » Despite this conserved 'two-handed' pattern of recognition, the RNA sequence is flexible. Among the binding sites of yeast Puf4p, RNA sequence dictates the pattern in which RNA bases are flipped away from the binding surface of the protein. Small differences in RNA sequence allow new modes of control, recruiting Puf5p in addition to Puf4p to a single site. This embedded information adds a new layer of biological meaning to the connections between RNA targets and PUF proteins.« less
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Mechanical energy storage device for hip disarticulation
NASA Technical Reports Server (NTRS)
Vallotton, W. C. (Inventor)
1977-01-01
An artificial leg including a trunk socket, a thigh section hingedly coupled to the trunk socket, a leg section hingedly coupled to the thigh section and a foot section hingedly coupled to the leg section is outlined. A mechanical energy storage device is operatively associated with the artificial leg for storage and release of energy during the normal walking stride of the user. Energy is stored in the mechanical energy storage device during a weight-bearing phase of the walking stride when the user's weight is on the artificial leg. Energy is released during a phase of the normal walking stride, when the user's weight is removed from the artificial leg. The stored energy is released from the energy storage device to pivot the thigh section forwardly about the hinged coupling to the trunk socket.
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Adaptive fiber optics collimator based on flexible hinges.
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.
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CALUTRON ASSEMBLING AND DISASSEMBLING APPARATUS
Andrews, R.E.
1959-01-27
A closure plate assembly is presented for a calutron tank. Due to the size and weight of the calutron tank a special face plate, hinges and latch construction are required. The salient feature of the invention is the provision of a face plate carrying the ion separating niechanism and adapted to close an open side of a calutron tank. A spring-type hinge secured to the face plate at one end prevents injury to the sealing gasket as the face plate is inserted and withdrawn. In additions a hinged support for the face plate comprises readily separable hinge elements, so that the face plate may first be swung outwardly from its operative position far enough to clear the ion separating meehanism carried thereby, and may thereafter be elevated and transported by a convcntional overhead crane.
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Rojo, Isabel; Teixidor, Francesc; Viñas, Clara; Kivekäs, Raikko; Sillanpää, Reijo
2004-10-25
The anionic chelating ligand [1,1'-(PPh2)2-3,3'-Co(1,2-C2B9H10)2]- has been synthesized from [3,3'-Co(1,2-C2B9H11)2]- in very good yield in a one-pot process with an easy work-up procedure. The coordinating ability of this ligand has been studied with Group 11 metal ions (Ag, Au) and with transition-metal ions (Pd, Rh). The two dicarbollide halves of the [1,1'-(PPh2)2-3,3'-Co(1,2-C2B9H10)2]- ligand can swing about one axis in a manner analogous to the constituent parts of BINAP and ferrocenyl phosphine derivatives. All these ligands function as hinges, with the most important property in relation to the coordination requirements of the metal being the PP distance. [1,1'-(PPh2)2-3,3'-Co(1,2-C2B9H10)2]-, BINAP, ferrocenyl phosphine derivatives, and other hinge ligands present a range of different PP separations, and consequently different coordination spheres and dispositions around metal cations. To account for these differences, the equation Dphi2 = D02 + 4 R2cos2(90-phi/2) has been developed. It relates the PP distance (Dphi) in a complex with the minimum PP distance (D0) that is characteristic of the hinge-type ligand.
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Zhang, Peijun; Meng, Xin; Zhao, Gongpu
2013-01-01
Helical structures are important in many different life forms and are well-suited for structural studies by cryo-EM. A unique feature of helical objects is that a single projection image contains all the views needed to perform a three-dimensional (3D) crystallographic reconstruction. Here, we use HIV-1 capsid assemblies to illustrate the detailed approaches to obtain 3D density maps from helical objects. Mature HIV-1 particles contain a conical- or tubular-shaped capsid that encloses the viral RNA genome and performs essential functions in the virus life cycle. The capsid is composed of capsid protein (CA) oligomers which are helically arranged on the surface. The N-terminal domain (NTD) of CA is connected to its C-terminal domain (CTD) through a flexible hinge. Structural analysis of two- and three-dimensional crystals provided molecular models of the capsid protein (CA) and its oligomer forms. We determined the 3D density map of helically assembled HIV-1 CA hexamers at 16 Å resolution using an iterative helical real-space reconstruction method. Docking of atomic models of CA-NTD and CA-CTD dimer into the electron density map indicated that the CTD dimer interface is retained in the assembled CA. Furthermore, molecular docking revealed an additional, novel CTD trimer interface. PMID:23132072
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BAF57 Modulation of Androgen Receptor Action and Prostate Cancer Progression
2007-12-01
mapped the AR binding site on BAF57 to the N-terminus (proline-rich region). Furthermore, the DBD and hinge region of AR also appear to play a...Accomplishments of Task 1: BAF57 binds to DNA binding domain ( DBD ) and hinge region of AR As outlined in the initial proposal, the first task...the above construct are the well-characterized zinc finger DNA binding domain ( DBD ) and the hinge region. Given the significant role of these two
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BAF57 Modulation of Androgen Receptor Action and Prostate Cancer Progression
2006-12-01
has fine mapped the AR binding site on BAF57 to the N-terminus (proline-rich region). Furthermore, the DBD and hinge region of AR also appear to...Accomplishments of Task 1: BAF57 binds to DNA binding domain ( DBD ) and hinge region of AR As outlined in the initial proposal, the first task was to...construct are the well-characterized zinc finger DNA binding domain ( DBD ) and the hinge region. Given the significant role of these two domains in AR
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Wire-Strain-Gage Hinge-Moment Indicators for Use in Tests of Airplane Models
NASA Technical Reports Server (NTRS)
Edwards, Howard B.
1944-01-01
The design and construction of various forms of strain-gage spring units and hinge-moment assemblies are discussed with particular reference to wind-tunnel test, although the indicators may be used equally well in flight tests. Strain-gage specifications are given, and the techniques of their application and use are described briefly. Testing, calibration and operation of hinge-moment indicators are discussed and precautions necessary for successful operation are stressed. Difficulties that may be encountered are summarized along with the possible causes.
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NASA Technical Reports Server (NTRS)
Miller, Eric J.; Cruz, Josue; Lung, Shun-Fat; Kota, Sridhar; Ervin, Gregory; Lu, Kerr-Jia; Flick, Pete
2016-01-01
A seamless adaptive compliant trailing edge (ACTE) flap was demonstrated in flight on a Gulfstream III aircraft at the NASA Armstrong Flight Research Center. The trailing edge flap was deflected between minus 2 deg up and plus 30 deg down in flight. The safety-of-flight parameters for the ACTE flap experiment require that flap-to-wing interface loads be sensed and monitored in real time to ensure that the structural load limits of the wing are not exceeded. The attachment fittings connecting the flap to the aircraft wing rear spar were instrumented with strain gages and calibrated using known loads for measuring hinge moment and normal force loads in flight. The safety-of-flight parameters for the ACTE flap experiment require that flap-to-wing interface loads be sensed and monitored in real time to ensure that the structural load limits of the wing are not exceeded. The attachment fittings connecting the flap to the aircraft wing rear spar were instrumented with strain gages and calibrated using known loads for measuring hinge moment and normal force loads in flight. The interface hardware instrumentation layout and load calibration are discussed. Twenty-one applied calibration test load cases were developed for each individual fitting. The 2-sigma residual errors for the hinge moment was calculated to be 2.4 percent, and for normal force was calculated to be 7.3 percent. The hinge moment and normal force generated by the ACTE flap with a hinge point located at 26-percent wing chord were measured during steady state and symmetric pitch maneuvers. The loads predicted from analysis were compared to the loads observed in flight. The hinge moment loads showed good agreement with the flight loads while the normal force loads calculated from analysis were over-predicted by approximately 20 percent. Normal force and hinge moment loads calculated from the pressure sensors located on the ACTE showed good agreement with the loads calculated from the installed strain gages.
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Lu, Yanling; Longman, Emma; Davis, Kenneth G.; Ortega, Álvaro; Grossmann, J. Günter; Michaelsen, Terje E.; de la Torre, José García; Harding, Stephen E.
2006-01-01
Crystallohydrodynamics describes the domain orientation in solution of antibodies and other multidomain protein assemblies where the crystal structures may be known for the domains but not the intact structure. The approach removes the necessity for an ad hoc assumed value for protein hydration. Previous studies have involved only the sedimentation coefficient leading to considerable degeneracy or multiplicity of possible models for the conformation of a given protein assembly, all agreeing with the experimental data. This degeneracy can be considerably reduced by using additional solution parameters. Conformation charts are generated for the three universal (i.e., size-independent) shape parameters P (obtained from the sedimentation coefficient or translational diffusion coefficient), ν (from the intrinsic viscosity), and G (from the radius of gyration), and calculated for a wide range of plausible orientations of the domains (represented as bead-shell ellipsoidal models derived from their crystal structures) and after allowance for any linker or hinge regions. Matches are then sought with the set of functions P, ν, and G calculated from experimental data (allowing for experimental error). The number of solutions can be further reduced by the employment of the Dmax parameter (maximum particle dimension) from x-ray scattering data. Using this approach we are able to reduce the degeneracy of possible solution models for IgG3 to a possible representative structure in which the Fab domains are directed away from the plane of the Fc domain, a structure in accord with the recognition that IgG3 is the most efficient complement activator among human IgG subclasses. PMID:16766619
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Vitrac, Heidi; Bogdanov, Mikhail; Heacock, Phil; Dowhan, William
2011-04-29
The N-terminal six-transmembrane domain (TM) bundle of lactose permease of Escherichia coli is uniformly inverted when assembled in membranes lacking phosphatidylethanolamine (PE). Inversion is dependent on the net charge of cytoplasmically exposed protein domains containing positive and negative residues, net charge of the membrane surface, and low hydrophobicity of TM VII acting as a molecular hinge between the two halves of lactose permease (Bogdanov, M., Xie, J., Heacock, P., and Dowhan, W. (2008) J. Cell Biol. 182, 925-935). Net neutral lipids suppress the membrane translocation potential of negatively charged amino acids, thus increasing the cytoplasmic retention potential of positively charged amino acids. Herein, TM organization of sucrose permease (CscB) and phenylalanine permease (PheP) as a function of membrane lipid composition was investigated to extend these principles to other proteins. For CscB, topological dependence on PE only becomes evident after a significant increase in the net negative charge of the cytoplasmic surface of the N-terminal TM bundle. High negative charge is required to overcome the thermodynamic block to inversion due to the high hydrophobicity of TM VII. Increasing the positive charge of the cytoplasmic surface of the N-terminal TM hairpin of PheP, which is misoriented in PE-lacking cells, favors native orientation in the absence of PE. PheP and CscB also display co-existing dual topologies dependent on changes in the charge balance between protein domains and the membrane lipids. Therefore, the topology of both permeases is dependent on PE. However, CscB topology is governed by thermodynamic balance between opposing lipid-dependent electrostatic and hydrophobic interactions.
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Beintema, J J; Peumans, W J
1992-03-09
The primary structure of stinging nettle (Urtica dioica) agglutinin has been determined by sequence analysis of peptides obtained from three overlapping proteolytic digests. The sequence of 80 residues consists of two hevein-like domains with the same spacing of half-cystine residues and several other conserved residues as observed earlier in other proteins with hevein-like domains. The hinge region between the two domains is four residues longer than those between the four domains in cereal lectins like wheat germ agglutinin.
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Gas turbine combustor exit piece with hinged connections
DOE Office of Scientific and Technical Information (OSTI.GOV)
Charron, Richard C.; Pankey, William W.
2016-04-26
An exit piece (66) with an inlet throat (67) that conducts a combustion gas flow (36A) in a path (82) from a combustor (63) to an annular chamber (68) that feeds the first blade section (37) of a gas turbine (26). The exit piece further includes an outlet portion (69) that forms a circumferential segment of the annular chamber. The outlet portion interconnects with adjacent outlet portions by hinges (78A, 78B, 80A, 80B). Each hinge may have a hinge axis (82A, 82B) parallel to a centerline (21) of the turbine. Respective gas flows (36A) are configured by an assembly (60)more » of the exit pieces to converge on the feed chamber (68) into a uniform helical flow that drives the first blade section with minimal circumferential variations in force.« less
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Progressive collapse of a two-story reinforced concrete frame with embedded smart aggregates
NASA Astrophysics Data System (ADS)
Laskar, Arghadeep; Gu, Haichang; Mo, Y. L.; Song, Gangbing
2009-07-01
This paper reports the experimental and analytical results of a two-story reinforced concrete frame instrumented with innovative piezoceramic-based smart aggregates (SAs) and subjected to a monotonic lateral load up to failure. A finite element model of the frame is developed and analyzed using a computer program called Open system for earthquake engineering simulation (OpenSees). The finite element analysis (FEA) is used to predict the load-deformation curve as well as the development of plastic hinges in the frame. The load-deformation curve predicted from FEA matched well with the experimental results. The sequence of development of plastic hinges in the frame is also studied from the FEA results. The locations of the plastic hinges, as obtained from the analysis, were similar to those observed during the experiment. An SA-based approach is also proposed to evaluate the health status of the concrete frame and identify the development of plastic hinges during the loading procedure. The results of the FEA are used to validate the SA-based approach for detecting the locations and occurrence of the plastic hinges leading to the progressive collapse of the frame. The locations and sequential development of the plastic hinges obtained from the SA-based approach corresponds well with the FEA results. The proposed SA-based approach, thus validated using FEA and experimental results, has a great potential to be applied in the health monitoring of large-scale civil infrastructures.
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Investigation on adaptive wing structure based on shape memory polymer composite hinge
NASA Astrophysics Data System (ADS)
Yu, Yuemin; Li, Xinbo; Zhang, Wei; Leng, Jinsong
2007-07-01
This paper describes the design and investigation of the SMP composite hinge and the morphing wing structure. The SMP composite hinge was based on SMP and carbon fiber fabric. The twisting recoverability of it was investigated by heating and then cooling repeatedly above and below the Tg. The twisting recoverability characterized by the twisting angle. Results show that the SMP composite hinge have good shape recoverability, Recovery time has a great influence on the twisting recoverability. The twisting recovery ratio became large with the increment of recovery time. The morphing wing can changes shape for different tasks. For the advantages of great recovery force and stable performances, we adopt SMP composite hinge as actuator to apply into the structure of the wing which can realize draw back wings to change sweep angle according to the speed and other requirements of military airplanes. Finally, a series of simulations and experiments are performed to investigate the deformations of morphing wings have been performed successfully. It can be seen that the sweep angle change became large with the increment of initial angle. The area reduction became large with the increment of initial angle, but after 75° the area reduction became smaller and smaller. The deformations of the triangle wing became large with the increment of temperature. The area and the sweep angle of wings can be controlled by adjusting the stimulate temperature and the initial twisting angle of shape memory polymer composite hinge.
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NASA Astrophysics Data System (ADS)
Manning, Andrew H.; Bartley, John M.
1994-06-01
Much of the recent debate over low-angle normal faults exposed in metamorphic core complexes has centered on the rolling hinge model. The model predicts tilting of seismogenic high-angle normal faults to lower dips by footwall deformation in response to isostatic forces caused by footwall exhumation. This shallow brittle deformation should visibly overprint the mylonitic fabric in the footwall of a metamorphic core complex. The predicted style and magnitude of rolling hinge strain depends upon the macroscopic mechanism by which the footwall deforms. Two end-members have been proposed: subvertical simple shear and flexural failure. Each mechanism should generate a distinctive pattern of structures that strike perpendicular to the regional extension direction. Subvertical simple shear (SVSS) should generate subvertical faults and kink bands with a shear sense antithetic to the detachment. For an SVSS hinge, the hinge-related strain magnitude should depend only on initial fault dip; rolling hinge structures should shorten the mylonitic foliation by >13% for an initial fault dip of >30°. In flexural failure the footwall behaves as a flexed elastic beam that partially fails in response to bending stresses. Resulting structures include conjugate faults and kink bands that both extend and contract the mylonitic foliation. Extensional sets could predominate as a result of superposition of far-field and flexural stresses. Strain magnitudes do not depend on fault dip but depend on the thickness and radius of curvature of the flexed footwall beam and vary with location within that beam. Postmylonitic structures were examined in the footwall of the Raft River metamorphic core complex in northwestern Utah to test these predictions. Observed structures strike perpendicular to the regional extension direction and include joints, normal faults, tension-gash arrays, and both extensional and contractional kink bands. Aside from the subvertical joints, the extensional structures dip moderately to steeply and are mainly either synthetic to the detachment or form conjugate sets. Range-wide, the extensional structures accomplish about 4% elongation of the mylonitic foliation. Contractional structures dip steeply, mainly record shear antithetic to the detachment, and accomplish <1% contraction of the foliation. These observations are consistent with the presence of a rolling hinge in the Raft River Mountains, but a rolling hinge that reoriented a high-angle normal fault by SVSS is excluded. The pattern and magnitudes of strain favor hinge-related deformation mainly by flexural failure with a subordinate component of SVSS.
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ERIC Educational Resources Information Center
Hsu, Nina S.; Kraemer, David J. M.; Oliver, Robyn T.; Schlichting, Margaret L.; Thompson-Schill, Sharon L.
2011-01-01
Neuroimaging tests of sensorimotor theories of semantic memory hinge on the extent to which similar activation patterns are observed during perception and retrieval of objects or object properties. The present study was motivated by the hypothesis that some of the seeming discrepancies across studies reflect flexibility in the systems responsible…
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NASA Technical Reports Server (NTRS)
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.
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Rowley, James P.; Lewandowski, Edward F.; Groh, Edward F.
1976-01-01
Three cylindrical rollers are rotatably mounted equidistant from the center of a hollow tool head on radii spaced 120.degree. apart. Each roller has a thin flange; the three flanges lie in a single plane to form an internal circumferential rib in a rotating tubular workpiece. The tool head has two complementary parts with two rollers in one part of the head and one roller in the other part; the two parts are joined by a hinge. A second hinge, located so the rollers are between the two hinges, connects one of the parts to a tool bar mounted in a lathe tool holder. The axes of rotation of both hinges and all three rollers are parallel. A hole exposing equal portions of the three roller flanges is located in the center of the tool head. The two hinges permit the tool head to be opened and rotated slightly downward, taking the roller flanges out of the path of the workpiece which is supported on both ends and rotated by the lathe. The parts of the tool head are then closed on the workpiece so that the flanges are applied to the workpiece and form the rib. The tool is then relocated for forming of the next rib.
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Jaeger, Gayle H; Wosar, Marc A; Marcellin-Little, Denis J; Lascelles, B Duncan X
2005-08-15
To describe placement of hinged transarticular external fixation (HTEF) frames and evaluate their ability to protect the primary repair of unstable joints while allowing joint mobility in dogs and cats. Retrospective study. 8 cats and 6 dogs. HTEF frames were composed of metal or epoxy connecting rods and a hinge. Measurements of range of motion of affected and contralateral joints and radiographs were made after fixator application and removal. 9 animals (4 cats and 5 dogs) had tarsal and 5 (4 cats and 1 dog) had stifle joint injuries. Treatment duration ranged from 45 to 100 days (median, 57 days). Ranges of motion in affected stifle and tarsal joints were 57% and 72% of control while HTEF was in place and 79% and 84% of control after frame removal. Complications were encountered in 3 cats and 2 dogs and included breakage of pins and connecting rods, hinge loosening, and failure at the hinge-epoxy interface. HTEF in animals with traumatic joint instability provided adjunctive joint stabilization during healing and protection of the primary repair and maintained joint motion during healing, resulting in early weight bearing of the affected limb.
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Vibration and shape control of hinged light structures using electromagnetic forces
NASA Astrophysics Data System (ADS)
Matsuzaki, Yuji; Miyachi, Shigenobu; Sasaki, Toshiyuki
2003-08-01
This paper describes a new electromagnetic device for vibration control of a light-weighted deployable/retractable structure which consists of many small units connected with mechanical hinges. A typical example of such a structure is a solar cell paddle of an artificial satellite which is composed of many thin flexible blankets connected in series. Vibration and shape control of the paddle is not easy, because control force and energy do not transmit well between the blankets which are discretely connected by hinges with each other. The new device consists of a permanent magnet glued along an edge of a blanket and an electric current-conducting coil glued along an adjoining edge of another adjacent blanket. Conduction of the electric current in a magnetic field from the magnet generates an electromagnetic force on the coil. By changing the current in the coil, therefore, we may control the vibration and shape of the blankets. To confirm the effectiveness of the new device, constructing a simple paddle model consisting eight hinge- panels, we have carried out a model experiment of vibration and shape control of the paddle. In addition, a numerical simulation of vibration control of the hinge structure is performed to compare with measured data.
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The E4 protein; structure, function and patterns of expression
DOE Office of Scientific and Technical Information (OSTI.GOV)
Doorbar, John, E-mail: jdoorba@nimr.mrc.ac.uk
2013-10-15
The papillomavirus E4 open reading frame (ORF) is contained within the E2 ORF, with the primary E4 gene-product (E1{sup ∧}E4) being translated from a spliced mRNA that includes the E1 initiation codon and adjacent sequences. E4 is located centrally within the E2 gene, in a region that encodes the E2 protein′s flexible hinge domain. Although a number of minor E4 transcripts have been reported, it is the product of the abundant E1{sup ∧}E4 mRNA that has been most extensively analysed. During the papillomavirus life cycle, the E1{sup ∧}E4 gene products generally become detectable at the onset of vegetative viral genomemore » amplification as the late stages of infection begin. E4 contributes to genome amplification success and virus synthesis, with its high level of expression suggesting additional roles in virus release and/or transmission. In general, E4 is easily visualised in biopsy material by immunostaining, and can be detected in lesions caused by diverse papillomavirus types, including those of dogs, rabbits and cattle as well as humans. The E4 protein can serve as a biomarker of active virus infection, and in the case of high-risk human types also disease severity. In some cutaneous lesions, E4 can be expressed at higher levels than the virion coat proteins, and can account for as much as 30% of total lesional protein content. The E4 proteins of the Beta, Gamma and Mu HPV types assemble into distinctive cytoplasmic, and sometimes nuclear, inclusion granules. In general, the E4 proteins are expressed before L2 and L1, with their structure and function being modified, first by kinases as the infected cell progresses through the S and G2 cell cycle phases, but also by proteases as the cell exits the cell cycle and undergoes true terminal differentiation. The kinases that regulate E4 also affect other viral proteins simultaneously, and include protein kinase A, Cyclin-dependent kinase, members of the MAP Kinase family and protein kinase C. For HPV16 E1{sup ∧}E4, these kinases regulate one of the E1{sup ∧}E4 proteins main functions, the association with the cellular keratin network, and eventually also its cleavage by the protease calpain which allows assembly into amyloid-like fibres and reorganisation of the keratin network. Although the E4 proteins of different HPV types appear divergent at the level of their primary amino acid sequence, they share a recognisable modular organisation and pattern of expression, which may underlie conserved functions and regulation. Assembly into higher-order multimers and suppression of cell proliferation are common to all E4 proteins examined. Although not yet formally demonstrated, a role in virus release and transmission remains a likely function for E4. - Highlights: • E4 gene products have a modular structure, and are expressed from the E1{sup ∧}E4 spliced mRNA. • E4 proteins are modified during epithelial differentiation by phosphorylation and proteolysis. • The E4 proteins contribute to genome amplification-efficiency and virus synthesis. • E4 proteins are abundantly expressed and may facilitate efficient virus release and transmission. • High-risk E4 proteins are deposited as amyloid fibres and can be used as infection biomarkers.« less
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Adjustable hinge permits movement of knee in plaster cast
NASA Technical Reports Server (NTRS)
Maley, W. E.
1967-01-01
Metal knee hinge with an adjustable sleeve worn on the outside of a leg cast facilitates movement of the knee joint. This helps eliminate stiffness of the knee and eliminates bulkiness and adjustment difficulty.
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Alicea, Ismael; Marvin, Jonathan S; Miklos, Aleksandr E; Ellington, Andrew D; Looger, Loren L; Schreiter, Eric R
2011-12-02
The phnD gene of Escherichia coli encodes the periplasmic binding protein of the phosphonate (Pn) uptake and utilization pathway. We have crystallized and determined structures of E. coli PhnD (EcPhnD) in the absence of ligand and in complex with the environmentally abundant 2-aminoethylphosphonate (2AEP). Similar to other bacterial periplasmic binding proteins, 2AEP binds near the center of mass of EcPhnD in a cleft formed between two lobes. Comparison of the open, unliganded structure with the closed 2AEP-bound structure shows that the two lobes pivot around a hinge by ~70° between the two states. Extensive hydrogen bonding and electrostatic interactions stabilize 2AEP, which binds to EcPhnD with low nanomolar affinity. These structures provide insight into Pn uptake by bacteria and facilitated the rational design of high signal-to-noise Pn biosensors based on both coupled small-molecule dyes and autocatalytic fluorescent proteins. Copyright © 2011 Elsevier Ltd. All rights reserved.
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Alicea, Ismael; Marvin, Jonathan S.; Miklos, Aleksandr E.; Ellington, Andrew D.; Looger, Loren L.; Schreiter, Eric R.
2012-01-01
The phnD gene of Escherichia coli encodes the periplasmic binding protein of the phosphonate uptake and utilization pathway. We have crystallized and determined structures of E. coli PhnD (EcPhnD) in the absence of ligand and in complex with the environmentally abundant 2-aminoethylphosphonate (2AEP). Similar to other bacterial periplasmic binding proteins, 2AEP binds near the center of mass of EcPhnD in a cleft formed between two lobes. Comparison of the open, unliganded structure with the closed 2AEP-bound structure shows that the two lobes pivot around a hinge by ~70° between the two states. Extensive hydrogen bonding and electrostatic interactions stabilize 2AEP, which binds to EcPhnD with low nanomolar affinity. These structures provide insight into phosphonate uptake by bacteria and facilitated the rational design of high signal-to-noise phosphonate biosensors based both on coupled small molecule dyes and autocatalytic fluorescent proteins. PMID:22019591
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Alicea, Ismael; Marvin, Jonathan S.; Miklos, Aleksandr E.
2012-09-17
The phnD gene of Escherichia coli encodes the periplasmic binding protein of the phosphonate (Pn) uptake and utilization pathway. We have crystallized and determined structures of E. coli PhnD (EcPhnD) in the absence of ligand and in complex with the environmentally abundant 2-aminoethylphosphonate (2AEP). Similar to other bacterial periplasmic binding proteins, 2AEP binds near the center of mass of EcPhnD in a cleft formed between two lobes. Comparison of the open, unliganded structure with the closed 2AEP-bound structure shows that the two lobes pivot around a hinge by {approx}70{sup o} between the two states. Extensive hydrogen bonding and electrostatic interactionsmore » stabilize 2AEP, which binds to EcPhnD with low nanomolar affinity. These structures provide insight into Pn uptake by bacteria and facilitated the rational design of high signal-to-noise Pn biosensors based on both coupled small-molecule dyes and autocatalytic fluorescent proteins.« less
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Limitations of Lifting-Line Theory for Estimation of Aileron Hinge-Moment Characteristics
NASA Technical Reports Server (NTRS)
Swanson, Robert S.; Gillis, Clarence L.
1943-01-01
Hinge-moment parameters for several typical ailerons were calculated from section data with the aspect-ratio correction as usually determined from lifting-line theory. The calculations showed that the agreement between experimental and calculated results was unsatisfactory. An additional aspect-ratio correction, calculated by the method of lifting-surface theory, was applied to the slope of the curve of hinge-moment coefficient against angle of attack at small angles of attack. This so-called streamline-curvature correction brought the calculated and experimental results into satisfactory agreement.
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NASA Technical Reports Server (NTRS)
Tang, M. H.; Pearson, G. P. E.
1973-01-01
Control-surface hinge-moment measurements obtained in the X-24A lifting body flight-test program are compared with results from wind-tunnel tests. The effects of variations in angle of attack, angle of sideslip, rudder bias, rudder deflection, upper-flap deflection, lower-flap deflection, Mach number, and rocket-engine operation on the control-surface hinge moments are presented. In-flight motion pictures of tufts attached to the inboard side of the right fin and the rudder and upper-flap surfaces are discussed.
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Dynamic stability of a helicopter with hinged rotor blades
NASA Technical Reports Server (NTRS)
Hohenemser, K
1939-01-01
The present report is a study of the dynamic stability of a helicopter with hinged rotor blades under hovering conditions. While in this case perfect stability can in general not be obtained it is possible by means of design features to prolong the period of the spontaneous oscillations of the helicopter and reduce their amplification, and so approximately assure neutral equilibrium. The possibility of controlled stability of a helicopter fitted with hinged blades is proved by the successful flights of various helicopters, particularly of the Focker FW61 helicopter.
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NASA Technical Reports Server (NTRS)
Hardin, R. B.; Burrows, R. R.
1975-01-01
A test is presented which was performed to determine the effect of cold jet gas plumes generated from main propulsion system and solid rocket motor nozzles on: (1) six-component force and moment data, (2) wing static pressures, (3) wing hinge moment, (4) elevon hinge moment, (5) rudder hinge moment, and (6) orbiter MPS nozzle pressure loads. The effects of rudder deflection, nozzle gimbal angle, and plume size were also obtained.
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Subsonic wind-tunnel measurements of a slender wing-body configuration employing a vortex flap
NASA Technical Reports Server (NTRS)
Frink, Neal T.
1987-01-01
A wind tunnel study at Mach 0.4 was conducted for a slender wing-body configuration with a leading edge vortex flap of curved planform that is deflectable about a 74 degree swept hinge line. The basic data consist of a unique combination of longitudinal aerodynamic, surface pressure, and vortex flap hinge-moment measurements on a common model. The longitudinal aerodynamic, pressure and hinge-moment data are presented without analysis in tabular format. Plots of the tabulated pressure data are also given.
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Means to flexibly attach lens frames to temple members
Smith, Harry D.
1995-01-01
The invention is a band hinge for flexibly connecting the temple member to the lens frame thereby preventing damage from inadvertent pressure or cyclic wear. A distinguishing feature of the invention is the use of a band hinge that holds together the temple member and the lens frame without the use of a pin or screw hinging mechanism. The invention allows for a high degree of freedom of movement for the temple member with respect to the lens frame which will prevent most forms of damages to the glasses from these types of events.
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Biomechanical Comparison of 3 Ankle Braces With and Without Free Rotation in the Sagittal Plane
Alfuth, Martin; Klein, Dieter; Koch, Raphael; Rosenbaum, Dieter
2014-01-01
Context: Various designs of braces including hinged and nonhinged models are used to provide external support of the ankle. Hinged ankle braces supposedly allow almost free dorsiflexion and plantar flexion of the foot in the sagittal plane. It is unclear, however, whether this additional degree of freedom affects the stabilizing effect of the brace in the other planes of motion. Objective: To investigate the dynamic and passive stabilizing effects of 3 ankle braces, 2 hinged models that provide free plantar flexion–dorsiflexion in the sagittal plane and 1 ankle brace without a hinge. Design: Crossover study. Setting: University Movement Analysis Laboratory. Patients or Other Participants: Seventeen healthy volunteers (5 women, 12 men; age = 25.4 ± 4.8 years; height = 180.3 ± 6.5 cm; body mass = 75.5 ± 10.4 kg). Intervention(s): We dynamically induced foot inversion on a tilting platform and passively induced foot movements in 6 directions via a custom-built apparatus in 3 brace conditions and a control condition (no brace). Main Outcome Measure(s): Maximum inversion was determined dynamically using an in-shoe electrogoniometer. Passively induced maximal joint angles were measured using a torque and angle sensor. We analyzed differences among the 4 ankle-brace conditions (3 braces, 1 control) for each of the dependent variables with Friedman and post hoc tests (P < .05). Results: Each ankle brace restricted dynamic foot-inversion movements on the tilting platform as compared with the control condition, whereas only the 2 hinged ankle braces differed from each other, with greater movement restriction caused by the Ankle X model. Passive foot inversion was reduced with all ankle braces. Passive plantar flexion was greater in the hinged models as compared with the nonhinged brace. Conclusions: All ankle braces showed stabilizing effects against dynamic and passive foot inversion. Differences between the hinged braces and the nonhinged brace did not appear to be clinically relevant. PMID:25098661
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NASA Technical Reports Server (NTRS)
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.
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Two-axis direct fluid shear stress sensor
NASA Technical Reports Server (NTRS)
Bajikar, Sateesh (Inventor); Scott, Michael A. (Inventor); Adcock, Edward E. (Inventor)
2011-01-01
A micro sized multi-axis semiconductor skin friction/wall shear stress induced by fluid flow. The sensor design includes a shear/strain transduction gimble connected to a force collecting plate located at the flow boundary surface. The shear force collecting plate is interconnected by an arm to offset the tortional hinges from the fluid flow. The arm is connected to the shear force collecting plate through dual axis torsional hinges with piezoresistive torsional strain gauges. These gauges are disposed on the tortional hinges and provide a voltage output indicative of applied shear stress acting on the force collection plate proximate the flow boundary surface. Offsetting the torsional hinges creates a force concentration and resolution structure that enables the generation of a large stress on the strain gauge from small shear stress, or small displacement of the collecting plate. The design also isolates the torsional sensors from exposure to the fluid flow.
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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 <0.05); the visual analogue scale (VAS) score at 1 day and 3 days after operation in group A were significantly less than those in group B ( P <0.05). Primary healing of incision was obtained in all patients of 2 groups, and no surgery-related complications occurred. The patients were followed up 6-24 months (mean, 12.3 months) in group A and 6-24 months (mean, 12.8 months) in group B. The self-evaluation satisfaction rate was 85.7% (12/14) in group A and was 81.2% (13/16) in group B at 3 months after operation, showing no significant difference ( χ 2 =0.055, P =0.990). Based on the improved Gassebaum elbow performance score at 6 months after operation, excellent and good rate of the elbow function was 78.6% (excellent in 5 cases, good in 6 cases, fair in 2 cases, and poor in 1 case) in group A and was 81.2% (excellent in 6 cases, good in 7 cases, fair in 2 cases, and poor in 1 case) in group B, showing no significant difference between 2 groups ( χ 2 =0.056, P =0.990). Heterotopic ossification occurred at 3 months after operation in 1 case of each group respectively. The X-ray films showed bony union in all cases; no loosening or breakage of screw was observed. The bone union time showed no significant difference between 2 groups ( t =-0.028, P =0.978). The time of 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 <0.05). The suspension fixation plus hinged 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.
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Phosphate binding protein as the biorecognition element in a biosensor for phosphate
NASA Technical Reports Server (NTRS)
Salins, Lyndon L E.; Deo, Sapna K.; Daunert, Sylvia
2004-01-01
This work explores the potential use of a member of the periplasmic family of binding proteins, the phosphate binding protein (PBP), as the biorecognition element in a sensing scheme for the detection of inorganic phosphate (Pi). The selectivity of this protein originates from its natural role which, in Escherichia coli, is to serve as the initial receptor for the highly specific translocation of Pi to the cytoplasm. The single polypeptide chain of PBP is folded into two similar domains connected by three short peptide linkages that serve as a hinge. The Pi binding site is located deep within the cleft between the two domains. In the presence of the ligand, the two globular domains engulf the former in a hinge-like manner. The resultant conformational change constitutes the basis of the sensor development. A mutant of PBP (MPBP), where an alanine was replaced by a cysteine residue, was prepared by site-directed mutagenesis using the polymerase chain reaction (PCR). The mutant was expressed, from plasmid pSD501, in the periplasmic space of E. coli and purified in a single chromatographic step on a perfusion anion-exchange column. Site-specific labeling was achieved by attaching the fluorophore, N-[2-(1-maleimidyl)ethyl]-7-(diethylamino)coumarin-3-carboxamide (MDCC), to the protein through the sulfhydryl group of the cysteine moiety. Steady-state fluorescence studies of the MPBP-MDCC conjugate showed a change in the intensity of the signal upon addition of Pi. Calibration curves for Pi were constructed by relating the intensity of the fluorescence signal with the amount of analyte present in the sample. The sensing system was first developed and optimized on a spectrofluorometer using ml volumes of sample. It was then adapted to be used on a microtiter plate arrangement with microliter sample volumes. The system's versatility was finally proven by developing a fiber optic fluorescence-based sensor for monitoring Pi. In all three cases the detection limits for the analyte were in the sub-microMolar range. It was also demonstrated that the sensing system was selective for phosphate over other structurally-similar anions, paving the way for the design and development of a new family of biosensors utilizing the specific binding properties of periplasmic proteins. c2003 Elsevier B.V. All rights reserved.
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Enhanced multimaterial 4D printing with active hinges
NASA Astrophysics Data System (ADS)
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.
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22. August 1974. BENCH SHOP, EAST WALL VIEW SHOWING HINGED ...
22. August 1974. BENCH SHOP, EAST WALL VIEW SHOWING HINGED PANEL AND WHEELPIT FOR MOUNTING SPOKES IN WHEEL HUB. - Gruber Wagon Works, Pennsylvania Route 183 & State Hill Road at Red Bridge Park, Bernville, Berks County, PA
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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 healing of the medial cortex.
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Heyberger, Clémence; Auberger, Guillaume; Babinet, Antoine; Anract, Philippe; Biau, David J
2017-12-21
We asked whether there would be any difference between primary and revision modern cemented fixed hinge megaprosthesis of the distal femur in function and activity-related outcomes following treatment of a bone tumor. An identical custom-made fixed hinge cemented megaprosthesis with a hydroxyapatite collar was used in all cases. The main outcomes were joint-specific function, disease-specific activity, and health-related quality of life. Implant survival was also evaluated. Patients in the revision group performed slightly better than patients in the primary group on disease-specific (Toronto Extremity Salvage Score, p = 0.033; Musculoskeletal Tumor Society, p = 0.072) and health-related outcomes (Short Form 36 [SF-36] physical component, p = 0.085; SF-36 mental component, p = 0.069) but not on joint-specific outcomes (Knee Society Score, p = 0.94). The cumulative probabilities of revision for any reason were 14.5% (7-25%) at 5 years with no statistically significant difference between primary and revision procedures ( p = 0.77). In conclusion, patients undergoing a revision have similar joint-specific functional outcome but improved disease-specific and health-related outcomes. Implant survival are similar between groups. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
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SnapDock—template-based docking by Geometric Hashing
Estrin, Michael; Wolfson, Haim J.
2017-01-01
Abstract Motivation: A highly efficient template-based protein–protein docking algorithm, nicknamed SnapDock, is presented. It employs a Geometric Hashing-based structural alignment scheme to align the target proteins to the interfaces of non-redundant protein–protein interface libraries. Docking of a pair of proteins utilizing the 22 600 interface PIFACE library is performed in < 2 min on the average. A flexible version of the algorithm allowing hinge motion in one of the proteins is presented as well. Results: To evaluate the performance of the algorithm a blind re-modelling of 3547 PDB complexes, which have been uploaded after the PIFACE publication has been performed with success ratio of about 35%. Interestingly, a similar experiment with the template free PatchDock docking algorithm yielded a success rate of about 23% with roughly 1/3 of the solutions different from those of SnapDock. Consequently, the combination of the two methods gave a 42% success ratio. Availability and implementation: A web server of the application is under development. Contact: michaelestrin@gmail.com or wolfson@tau.ac.il PMID:28881968
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Coupling for joining a ball nut to a machine tool carriage
Gerth, Howard L.
1979-01-01
The present invention relates to an improved coupling for joining a lead screw ball nut to a machine tool carriage. The ball nut is coupled to the machine tool carriage by a plurality of laterally flexible bolts which function as hinges during the rotation of the lead screw for substantially reducing lateral carriage movement due to wobble in the lead screw.
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NASA Technical Reports Server (NTRS)
Rignot, Eric
1998-01-01
The synthetic-aperture radar interferometry technique is used to detect the migration of the limit of tidal flexing, or hinge line, of the floating ice tongue of Petermann Gletscher, a major outlet glacier of north Greenland.
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14 CFR 25.393 - Loads parallel to hinge line.
Code of Federal Regulations, 2010 CFR
2010-01-01
... designed for inertia loads acting parallel to the hinge line. (b) In the absence of more rational data, the inertia loads may be assumed to be equal to KW, where— (1) K=24 for vertical surfaces; (2) K=12 for...
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14 CFR 25.393 - Loads parallel to hinge line.
Code of Federal Regulations, 2012 CFR
2012-01-01
... designed for inertia loads acting parallel to the hinge line. (b) In the absence of more rational data, the inertia loads may be assumed to be equal to KW, where— (1) K=24 for vertical surfaces; (2) K=12 for...
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14 CFR 25.393 - Loads parallel to hinge line.
Code of Federal Regulations, 2011 CFR
2011-01-01
... designed for inertia loads acting parallel to the hinge line. (b) In the absence of more rational data, the inertia loads may be assumed to be equal to KW, where— (1) K=24 for vertical surfaces; (2) K=12 for...
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14 CFR 25.393 - Loads parallel to hinge line.
Code of Federal Regulations, 2014 CFR
2014-01-01
... designed for inertia loads acting parallel to the hinge line. (b) In the absence of more rational data, the inertia loads may be assumed to be equal to KW, where— (1) K=24 for vertical surfaces; (2) K=12 for...
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14 CFR 25.393 - Loads parallel to hinge line.
Code of Federal Regulations, 2013 CFR
2013-01-01
... designed for inertia loads acting parallel to the hinge line. (b) In the absence of more rational data, the inertia loads may be assumed to be equal to KW, where— (1) K=24 for vertical surfaces; (2) K=12 for...
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Fabrication and Assembly of High-Precision Hinge and Latch Joints for Deployable Optical Instruments
NASA Technical Reports Server (NTRS)
Phelps, James E.
1999-01-01
Descriptions are presented of high-precision hinge and latch joints that have been co-developed, for application to deployable optical instruments, by NASA Langley Research Center and Nyma/ADF. Page-sized versions of engineering drawings are included in two appendices to describe all mechanical components of both joints. Procedures for assembling the mechanical components of both joints are also presented. The information herein is intended to facilitate the fabrication and assembly of the high-precision hinge and latch joints, and enable the incorporation of these joints into the design of deployable optical instrument systems.
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Mechanics Model for Simulating RC Hinges under Reversed Cyclic Loading
Shukri, Ahmad Azim; Visintin, Phillip; Oehlers, Deric J.; Jumaat, Mohd Zamin
2016-01-01
Describing the moment rotation (M/θ) behavior of reinforced concrete (RC) hinges is essential in predicting the behavior of RC structures under severe loadings, such as under cyclic earthquake motions and blast loading. The behavior of RC hinges is defined by localized slip or partial interaction (PI) behaviors in both the tension and compression region. In the tension region, slip between the reinforcement and the concrete defines crack spacing, crack opening and closing, and tension stiffening. While in the compression region, slip along concrete to concrete interfaces defines the formation and failure of concrete softening wedges. Being strain-based, commonly-applied analysis techniques, such as the moment curvature approach, cannot directly simulate these PI behaviors because they are localized and displacement based. Therefore, strain-based approaches must resort to empirical factors to define behaviors, such as tension stiffening and concrete softening hinge lengths. In this paper, a displacement-based segmental moment rotation approach, which directly simulates the partial interaction behaviors in both compression and tension, is developed for predicting the M/θ response of an RC beam hinge under cyclic loading. Significantly, in order to develop the segmental approach, a partial interaction model to predict the tension stiffening load slip relationship between the reinforcement and the concrete is developed. PMID:28773430
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Seismic Performance Evaluation of Reinforced Concrete Frames Subjected to Seismic Loads
NASA Astrophysics Data System (ADS)
Zameeruddin, Mohd.; Sangle, Keshav K.
2017-06-01
Ten storied-3 bays reinforced concrete bare frame designed for gravity loads following the guidelines of IS 456 and IS 13920 for ductility is subjected to seismic loads. The seismic demands on this building were calculated by following IS 1893 for response spectra of 5% damping (for hard soil type). Plastic hinges were assigned to the beam and column at both ends to represent the failure mode, when member yields. Non-linear static (pushover) analysis was performed to evaluate the performance of the building in reference to first (ATC 40), second (FEMA 356) and next-generation (FEMA 440) performance based seismic design procedures. Base shear against top displacement curve of structure, known as pushover curve was obtained for two actions of plastic hinge behavior, force-controlled (brittle) and deformation-controlled (ductile) actions. Lateral deformation corresponding to performance point proves the building capability to sustain a certain level of seismic loads. The failure is represented by a sequence of formation of plastic hinges. Deformation-controlled action of hinges showed that building behaves like strong-column-weak-beam mechanism, whereas force-controlled action showed formation of hinges in the column. The study aims to understand the first, second and next generation performance based design procedure in prediction of actual building responses and their conservatism into the acceptance criteria.
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Mechanics Model for Simulating RC Hinges under Reversed Cyclic Loading.
Shukri, Ahmad Azim; Visintin, Phillip; Oehlers, Deric J; Jumaat, Mohd Zamin
2016-04-22
Describing the moment rotation (M/θ) behavior of reinforced concrete (RC) hinges is essential in predicting the behavior of RC structures under severe loadings, such as under cyclic earthquake motions and blast loading. The behavior of RC hinges is defined by localized slip or partial interaction (PI) behaviors in both the tension and compression region. In the tension region, slip between the reinforcement and the concrete defines crack spacing, crack opening and closing, and tension stiffening. While in the compression region, slip along concrete to concrete interfaces defines the formation and failure of concrete softening wedges. Being strain-based, commonly-applied analysis techniques, such as the moment curvature approach, cannot directly simulate these PI behaviors because they are localized and displacement based. Therefore, strain-based approaches must resort to empirical factors to define behaviors, such as tension stiffening and concrete softening hinge lengths. In this paper, a displacement-based segmental moment rotation approach, which directly simulates the partial interaction behaviors in both compression and tension, is developed for predicting the M/θ response of an RC beam hinge under cyclic loading. Significantly, in order to develop the segmental approach, a partial interaction model to predict the tension stiffening load slip relationship between the reinforcement and the concrete is developed.
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Shock Location Dominated Transonic Flight Loads on the Active Aeroelastic Wing
NASA Technical Reports Server (NTRS)
Lokos, William A.; Lizotte, Andrew; Lindsley, Ned J.; Stauf, Rick
2005-01-01
During several Active Aeroelastic Wing research flights, the shadow of the over-wing shock could be observed because of natural lighting conditions. As the plane accelerated, the shock location moved aft, and as the shadow passed the aileron and trailing-edge flap hinge lines, their associated hinge moments were substantially affected. The observation of the dominant effect of shock location on aft control surface hinge moments led to this investigation. This report investigates the effect of over-wing shock location on wing loads through flight-measured data and analytical predictions. Wing-root and wing-fold bending moment and torque and leading- and trailing-edge hinge moments have been measured in flight using calibrated strain gages. These same loads have been predicted using a computational fluid dynamics code called the Euler Navier-Stokes Three Dimensional Aeroelastic Code. The computational fluid dynamics study was based on the elastically deformed shape estimated by a twist model, which in turn was derived from in-flight-measured wing deflections provided by a flight deflection measurement system. During level transonic flight, the shock location dominated the wing trailing-edge control surface hinge moments. The computational fluid dynamics analysis based on the shape provided by the flight deflection measurement system produced very similar results and substantially correlated with the measured loads data.
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NASA Astrophysics Data System (ADS)
Siegesmund, S.; Vollbrecht, A.; Pros, Z.
1993-10-01
The complete P-wave velocity distribution, preferred orientation of rock-forming minerals and microcracks of two differently deformed orthogneisses from the Kutna Hora Crystalline Unit were investigated. The complete symmetry of P-wave velocities were determined as a function of confining pressure on the basis of 132 independent propagation directions up to 400 MPa. The two samples are of almost identical mineralogical composition, but exhibit different fabrics which can be related to different positions within a large-scale fold structure. The symmetry of the Vp-diagrams change from nearly transversely isotropic for the sample from the limb area to orthorhombic for the sample from the hinge zone, which shows an additional crenulation cleavage. This change of symmetry is observed at all pressure levels. Reorientation of the main velocity directions ( Vpmin, Vpmax, Kpint) between hinge and limb is controlled by the microcrack fabric and the texture of the rock-forming minerals. This can cause significant differences in reflectivity related to fabric changes within large-scale folds.
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Structure and evolutionary aspects of matrix metalloproteinases: a brief overview.
Das, Sudip; Mandal, Malay; Chakraborti, Tapati; Mandal, Amritlal; Chakraborti, Sajal
2003-11-01
The matrix metalloproteinases (MMPs) are zinc dependent endopeptidases known for their ability to cleave one or several extracellular matrix (ECM) constituents, as well as non-matrix proteins. They comprise a large family of proteinases that share common structural and functional elements and are products of different genes. All members of this family contain a signal peptide, a propeptide and a catalytic domain. The catalytic domain contains two zinc ions and at least one calcium ion coordinated to various residues. All MMPs, with the exception matrilysin, have a hemopexin/vitronectin-like domain that is connected to the catalytic domain by a hinge or linker region. The hemopexin-like domain influences tissue inhibitor of metalloproteinases (TIMP) binding, the binding of certain substrates, membrane activation, and some proteolytic activities. It has been proposed that the origin of MMPs could be traced to before the emergence of vertebrates from invertebrates. It appears conceivable that the domain assemblies occurred at an early stage of the diversification of different MMPs and that they progressed through the evolutionary process independent of one another, and perhaps parallel to each other.
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Kuhn, Claus-D
2016-05-01
tRNAs undergo multiple conformational changes during the translation cycle that are required for tRNA translocation and proper communication between the ribosome and translation factors. Recent structural data on how destabilized tRNAs utilize the CCA-adding enzyme to proofread themselves put a spotlight on tRNA flexibility beyond the translation cycle. In analogy to tRNA surveillance, this review finds that other processes also exploit versatile tRNA folding to achieve, amongst others, specific aminoacylation, translational regulation by riboswitches or a block of bacterial translation. tRNA flexibility is thereby not restricted to the hinges utilized during translation. In contrast, the flexibility of tRNA is distributed all over its L-shape and is actively exploited by the tRNA-interacting partners to discriminate one tRNA from another. Since the majority of tRNA modifications also modulate tRNA flexibility it seems that cells devote enormous resources to tightly sense and regulate tRNA structure. This is likely required for error-free protein synthesis. © 2016 WILEY Periodicals, Inc.
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Photo-switchable tweezers illuminate pore-opening motions of an ATP-gated P2X ion channel
Habermacher, Chloé; Martz, Adeline; Calimet, Nicolas; Lemoine, Damien; Peverini, Laurie; Specht, Alexandre; Cecchini, Marco; Grutter, Thomas
2016-01-01
P2X receptors function by opening a transmembrane pore in response to extracellular ATP. Recent crystal structures solved in apo and ATP-bound states revealed molecular motions of the extracellular domain following agonist binding. However, the mechanism of pore opening still remains controversial. Here we use photo-switchable cross-linkers as ‘molecular tweezers’ to monitor a series of inter-residue distances in the transmembrane domain of the P2X2 receptor during activation. These experimentally based structural constraints combined with computational studies provide high-resolution models of the channel in the open and closed states. We show that the extent of the outer pore expansion is significantly reduced compared to the ATP-bound structure. Our data further reveal that the inner and outer ends of adjacent pore-lining helices come closer during opening, likely through a hinge-bending motion. These results provide new insight into the gating mechanism of P2X receptors and establish a versatile strategy applicable to other membrane proteins. DOI: http://dx.doi.org/10.7554/eLife.11050.001 PMID:26808983
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The Pim kinases: new targets for drug development.
Swords, Ronan; Kelly, Kevin; Carew, Jennifer; Nawrocki, Stefan; Mahalingam, Devalingam; Sarantopoulos, John; Bearss, David; Giles, Francis
2011-12-01
The three Pim kinases are a small family of serine/threonine kinases regulating several signaling pathways that are fundamental to cancer development and progression. They were first recognized as pro-viral integration sites for the Moloney Murine Leukemia virus. Unlike other kinases, they possess a hinge region which creates a unique binding pocket for ATP. Absence of a regulatory domain means that these proteins are constitutively active once transcribed. Pim kinases are critical downstream effectors of the ABL (ableson), JAK2 (janus kinase 2), and Flt-3 (FMS related tyrosine kinase 1) oncogenes and are required by them to drive tumorigenesis. Recent investigations have established that the Pim kinases function as effective inhibitors of apoptosis and when overexpressed, produce resistance to the mTOR (mammalian target of rapamycin) inhibitor, rapamycin . Overexpression of the PIM kinases has been reported in several hematological and solid tumors (PIM 1), myeloma, lymphoma, leukemia (PIM 2) and adenocarcinomas (PIM 3). As such, the Pim kinases are a very attractive target for pharmacological inhibition in cancer therapy. Novel small molecule inhibitors of the human Pim kinases have been designed and are currently undergoing preclinical evaluation.
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Watanabe, Takanori; Kessler, Daniel; Scott, Clayton; Angstadt, Michael; Sripada, Chandra
2014-01-01
Substantial evidence indicates that major psychiatric disorders are associated with distributed neural dysconnectivity, leading to strong interest in using neuroimaging methods to accurately predict disorder status. In this work, we are specifically interested in a multivariate approach that uses features derived from whole-brain resting state functional connectomes. However, functional connectomes reside in a high dimensional space, which complicates model interpretation and introduces numerous statistical and computational challenges. Traditional feature selection techniques are used to reduce data dimensionality, but are blind to the spatial structure of the connectomes. We propose a regularization framework where the 6-D structure of the functional connectome (defined by pairs of points in 3-D space) is explicitly taken into account via the fused Lasso or the GraphNet regularizer. Our method only restricts the loss function to be convex and margin-based, allowing non-differentiable loss functions such as the hinge-loss to be used. Using the fused Lasso or GraphNet regularizer with the hinge-loss leads to a structured sparse support vector machine (SVM) with embedded feature selection. We introduce a novel efficient optimization algorithm based on the augmented Lagrangian and the classical alternating direction method, which can solve both fused Lasso and GraphNet regularized SVM with very little modification. We also demonstrate that the inner subproblems of the algorithm can be solved efficiently in analytic form by coupling the variable splitting strategy with a data augmentation scheme. Experiments on simulated data and resting state scans from a large schizophrenia dataset show that our proposed approach can identify predictive regions that are spatially contiguous in the 6-D “connectome space,” offering an additional layer of interpretability that could provide new insights about various disease processes. PMID:24704268
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28. BRIDGE NO. 9 APRON AND BRIDGE HINGE JOINT AND ...
28. BRIDGE NO. 9 APRON AND BRIDGE HINGE JOINT AND BRIDGE SUSPENSION SYSTEM SHOWING EYEBAR AND CABLE CONNECTIONS. LOOKING WEST. - Greenville Yard, Transfer Bridge System, Port of New York/New Jersey, Upper New York Bay, Jersey City, Hudson County, NJ
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DETAIL OF ORIGINAL SLIDING DOORS ALTERED WITH OPENING FOR HINGED ...
DETAIL OF ORIGINAL SLIDING DOORS ALTERED WITH OPENING FOR HINGED DOOR. WITH GRADUATED SCALE IN 1' INCREMENTS. VIEW FACING NORTHWEST - U.S. Naval Base, Pearl Harbor, Gymnasium Building, North Waterfront & Pierce Street near Berth S-13, Pearl City, Honolulu County, HI
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Three-Dimensional Printing of Surgical Clips: An In Vitro Pilot Study and Trial of Efficacy.
Canvasser, Noah E; De, Shuvro; Koseoglu, Ersin; Lay, Aaron H; Sorokin, Igor; Fernandez, Raul; Cadeddu, Jeffrey A
2017-09-01
Three-dimensional (3D) printing applications have increased over the past decade. Our objective was to test rapid prototyping of a 3D printed surgical clip for intraoperative use. Our prototype was modeled after the 10 mm Weck ® Hem-o-lok ® polymer clip (Teleflex, Inc., Wayne, PA). A 3D computer-aided design model of the Hem-o-lok clip was reverse engineered using commercial microscopy and printing was done using an Objet Connex500 multijetting system (Stratasys, Eden Prairie, MN). The initial polymer was Objet VeroWhitePlus RGD835; the addition of Objet TangoBlackPlus FLX980 during the design process improved hinge flexibility. The 3D printed clips were then pressure tested on rubber Penrose tubing and compared in vitro versus commercial Hem-o-lok clips. Initial 3D printed clips were not functional as they split at the hinge upon closure of the clip jaws. Design changes were made to add Objet TangoBlackPlus FLX980 at the hinge to improve flexibility. Additional modifications were made to allow for clips to be compatible with the Hem-o-lok endoscopic clip applier. A total of 50 clips were tested. Fracture rate for the printed clips using a clip applier was 54% (n = 27), whereas none of the commercial Hem-o-lok clips broke upon closure. Of the 23 printed clips that closed, mean leak was at 20.7 κPa (range 4.8-42.7). In contrast, none of the commercial clips leaked, and fill continued until Penrose rupture at mean 46.2 κPa (44.8-47.6). This pilot study demonstrates feasibility of 3D printing functional surgical clips. However, the performance of our first generation clips is poor compared with commercial grade product. Refinement in printers and materials available may allow for customization of such printed surgical instruments that could be economically competitive to purchasing and stocking product.
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Non-equivalent role of TM2 gating hinges in heteromeric Kir4.1/Kir5.1 potassium channels
Shang, Lijun
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 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 α-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. PMID:17657484
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The effects of klapskate hinge position on push-off performance: a simulation study.
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.
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Bertocci, Gina E; Brown, Nathan P; Mich, Patrice M
2017-01-01
OBJECTIVE To evaluate effects of an orthosis on biomechanics of a cranial cruciate ligament (CrCL)-deficient canine stifle joint by use of a 3-D quasistatic rigid-body pelvic limb computer model simulating the stance phase of gait and to investigate influences of orthosis hinge stiffness (durometer). SAMPLE A previously developed computer simulation model for a healthy 33-kg 5-year-old neutered Golden Retriever. PROCEDURES A custom stifle joint orthosis was implemented in the CrCL-deficient pelvic limb computer simulation model. Ligament loads, relative tibial translation, and relative tibial rotation in the orthosis-stabilized stifle joint (baseline scenario; high-durometer hinge]) were determined and compared with values for CrCL-intact and CrCL-deficient stifle joints. Sensitivity analysis was conducted to evaluate the influence of orthosis hinge stiffness on model outcome measures. RESULTS The orthosis decreased loads placed on the caudal cruciate and lateral collateral ligaments and increased load placed on the medial collateral ligament, compared with loads for the CrCL-intact stifle joint. Ligament loads were decreased in the orthosis-managed CrCL-deficient stifle joint, compared with loads for the CrCL-deficient stifle joint. Relative tibial translation and rotation decreased but were not eliminated after orthosis management. Increased orthosis hinge stiffness reduced tibial translation and rotation, whereas decreased hinge stiffness increased internal tibial rotation, compared with values for the baseline scenario. CONCLUSIONS AND CLINICAL RELEVANCE Stifle joint biomechanics were improved following orthosis implementation, compared with biomechanics of the CrCL-deficient stifle joint. Orthosis hinge stiffness influenced stifle joint biomechanics. An orthosis may be a viable option to stabilize a CrCL-deficient canine stifle joint.
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Experimental and Numerical Assessment of a New Alternative of RBS Moment Connection
DOE Office of Scientific and Technical Information (OSTI.GOV)
Mirghaderi, Rasoul; Imanpour, Ali; Keshavarzi, Farhad
2008-07-08
Reduced beam section (RBS) connection has been known as a famous connection for steel moment-resisting seismic frames in high-rise buildings, because of their economical advantages and seismic ductility. In the ordinary RBS connection, often portions of the beam flanges are selectively trimmed in the region adjacent to the beam-to-column connection, and beam section is weakened in the plastic hinge region; section weakening concept in the plastic hinge region of beam cause to reduction of beam plastic section modulus in this region, and force plastic hinge to occur within the reduced section.This paper presents a new alternative of RBS connection thatmore » has been used aforesaid weakening concept in it, with this difference that corrugated steel plate webs instead of beam flange cutting has been used in limited specific length near the column face. Corrugated steel plates because of their accordion effect don't have bending rigidity, then using of these plates in plastic hinge region reduces the beam plastic section modulus and plastic hinge is formed in corrugated region. For investigating the seismic behavior and performance of new RBS moment connection, experimental specimen of new RBS connection were subjected to cyclic load, and finite element analysis were executed. The result of cyclic test and numerical analysis specified that the corrugated webs improved the plastic stability and provided capability of large plastic rotation at the plastic hinge location without any appreciable buckling and brittle fractures in this region. The test observations also showed that the specimens' plastic rotations exceeded 0.04 rad without any local and global buckling. All of the analytical results for proposed connection are generally in good agreement with the test observations.« less
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PLAN2D - A PROGRAM FOR ELASTO-PLASTIC ANALYSIS OF PLANAR FRAMES
NASA Technical Reports Server (NTRS)
Lawrence, C.
1994-01-01
PLAN2D is a FORTRAN computer program for the plastic analysis of planar rigid frame structures. Given a structure and loading pattern as input, PLAN2D calculates the ultimate load that the structure can sustain before collapse. Element moments and plastic hinge rotations are calculated for the ultimate load. The location of hinges required for a collapse mechanism to form are also determined. The program proceeds in an iterative series of linear elastic analyses. After each iteration the resulting elastic moments in each member are compared to the reserve plastic moment capacity of that member. The member or members that have moments closest to their reserve capacity will determine the minimum load factor and the site where the next hinge is to be inserted. Next, hinges are inserted and the structural stiffness matrix is reformulated. This cycle is repeated until the structure becomes unstable. At this point the ultimate collapse load is calculated by accumulating the minimum load factor from each previous iteration and multiplying them by the original input loads. PLAN2D is based on the program STAN, originally written by Dr. E.L. Wilson at U.C. Berkeley. PLAN2D has several limitations: 1) Although PLAN2D will detect unloading of hinges it does not contain the capability to remove hinges; 2) PLAN2D does not allow the user to input different positive and negative moment capacities and 3) PLAN2D does not consider the interaction between axial and plastic moment capacity. Axial yielding and buckling is ignored as is the reduction in moment capacity due to axial load. PLAN2D is written in FORTRAN and is machine independent. It has been tested on an IBM PC and a DEC MicroVAX. The program was developed in 1988.
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[ANALYSIS OF IMPLANT-RELATED COMPLICATIONS AFTER HINGE KNEE REPLACEMENT FOR TUMORS AROUND THE KNEE].
Li, Dong; Ma, Huanzhi; Zhang, Wei; Sun, Chengliang; Lu, Xiaoyong; Gao, Yutong; Zhou, Dongsheng
2015-08-01
To investigate the reasons and managements of implant-related complications after hinge knee replacement for tumors around the knee. A retrospective analysis was made on the clinical data of 96 patients undergoing hinge knee replacement between January 2000 and December 2012. There were 64 males and 32 females with the mean age of 31.0 years (range, 15-72 years). The most common tumor type was osteosarcoma (72 cases), and the second was giant cell tumor (15 cases). The tumor located at the distal femurs in 52 cases and at the proximal tibias in 44 cases. Fifteen hinge and 81 rotating hinge prostheses were used. The recurrence, metastasis, and survival were recorded. The implant-related complications were observed. The median follow-up time was 43.5 months (range, 10-156 months). Complications were observed in 21 patients (25 implant-related complications); 13 complications located at the femur and 12 complications at the tibia. The complications included aseptic loosening (8 cases), deep infection (7 cases), prosthetic breakage (4 cases), peri-prosthetic fracture (2 cases), and dislocation (4 cases). Most deep infection occurred within 12 months after operation (6/7), and most aseptic loosening after 40 months of operation (6/8). The rate of limb salvage was 90.6% (87/96) and the amputation rate was 9.4% (9/96). The overall survival rate of the prosthesis was 76.7% (5-year) and 47.2% (10-year). The 5-year survival rate was 82.9% for femoral prosthesis and 71.0% for tibial prosthesis, showing no significant difference (P = 0.954). Hinge knee prosthesis still has a high rate of complications. Deep infection is main reason to decrease short-term prosthetic survival rate, and aseptic loosening shortens the long-short prosthetic survival time.
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29. BRIDGE NO. 13 APRON AND BRIDGE HINGE JOINT AND ...
29. BRIDGE NO. 13 APRON AND BRIDGE HINGE JOINT AND BRIDGE SUSPENSION SYSTEM (OLDER STYLE) SHOWING EYEBAR AND CABLE CONNECTIONS. LOOKING WEST. - Greenville Yard, Transfer Bridge System, Port of New York/New Jersey, Upper New York Bay, Jersey City, Hudson County, NJ
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10 CFR 431.62 - Definitions concerning commercial refrigerators, freezers and refrigerator-freezers.
Code of Federal Regulations, 2012 CFR
2012-01-01
... transparent or solid doors, sliding or hinged doors, a combination of hinged, sliding, transparent, or solid... compressors, refrigerant condensers, condenser fans and motors, and factory supplied accessories. Self... more refrigerant compressors, refrigerant condensers, condenser fans and motors, and factory supplied...
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Modal identities for multibody elastic spacecraft: An aid to selecting modes for simulation
NASA Technical Reports Server (NTRS)
Hablani, Hari B.
1989-01-01
The question: Which set of modes furnishes a higher fidelity math model of dynamics of a multibody, deformable spacecraft (hinges-free or hinges-locked vehicle modes) is answered. Two sets of general, discretized, linear equations of motion of a spacecraft with an arbitrary number of deformable appendages, each articulated directly to the core body, are obtained using the above two families of modes. By a comparison of these equations, ten sets of modal identities are constructed which involve modal momenta coefficients and frequencies associated with both classes of modes. The sums of infinite series that appear in the identities are obtained in terms of mass, and first and second moments of inertia of the appendages, core body, and vehicle by using certain basic identities concerning appendage modes. Applying the above identities to a four-body spacecraft, the hinges-locked vehicle modes are found to yield a higher fidelity model than hinges-free modes, because the latter modes have nonconverging modal coefficients; a characteristic proved and illustrated.
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Ultra-precise micro-motion stage for optical scanning test
NASA Astrophysics Data System (ADS)
Chen, Wen; Zhang, Jianhuan; Jiang, Nan
2009-05-01
This study aims at the application of optical sensing technology in a 2D flexible hinge test stage. Optical fiber sensor which is manufactured taking advantage of the various unique properties of optical fiber, such as good electric insulation properties, resistance of electromagnetic disturbance, sparkless property and availability in flammable and explosive environment, has lots of good properties, such as high accuracy and wide dynamic range, repeatable, etc. and is applied in 2D flexible hinge stage driven by PZT. Several micro-bending structures are designed utilizing the characteristics of the flexible hinge stage. And through experiments, the optimal micro-bending tooth structure and the scope of displacement sensor trip under this optimal micro-bending tooth structure are derived. These experiments demonstrate that the application of optical fiber displacement sensor in 2D flexible hinge stage driven by PZT substantially broadens the dynamic testing range and improves the sensitivity of this apparatus. Driving accuracy and positioning stability are enhanced as well. [1,2
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Schulz, Sebastian; Doller, Anke; Pendini, Nicole R; Wilce, Jacqueline A; Pfeilschifter, Josef; Eberhardt, Wolfgang
2013-12-01
The ubiquitous mRNA binding protein human antigen R (HuR) participates in the post-transcriptional regulation of many AU-rich element (ARE)-bearing mRNAs. Previously, by using in vitro kinase assay, we have identified serines (Ser) 158, 221 and 318 as targets of protein kinase C (PKC)-triggered phosphorylation. In this study, we tested whether GFP- or GST-tagged HuR constructs bearing a phosphomimetic Ser (S)-to-Asp (D) substitution at the different PKC target sites, would affect different HuR functions including HuR nucleo-cytoplasmic redistribution and binding to different types of ARE-containing mRNAs. The phosphomimetic GFP-tagged HuR protein bearing a phosphomimetic substitution in the hinge region of HuR (HuR-S221D) showed an increased cytoplasmic abundance when compared to wild-type HuR. Conversely, data from in vitro kinase assay and electrophoretic mobility shift assay (EMSA), implicates that phosphorylation at Ser 221 is not relevant for mRNA binding of HuR. Quantification of in vitro binding affinities of GST-tagged wild-type HuR and corresponding HuR proteins bearing a phosphomimetic substitution in either RRM2 (HuR-S158D) or in RRM3 (HuR-S318D) by microscale thermophoresis (MST) indicates a specific binding of wild-type HuR to type I, II or type III-ARE-oligonucleotides in the high nanomolar range. Interestingly, phosphomimetic mutation at position 158 or 318 had a negative influence on HuR binding to type I- and type II-ARE-mRNAs whereas it significantly enhanced HuR affinity to a type III-ARE substrate. Our data suggest that differential phosphorylation of HuR by PKCs at different HuR domains coordinates subcellular HuR distribution and leads to a preferential binding to U-rich bearing target mRNA. © 2013.
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NASA Astrophysics Data System (ADS)
Bajaj, Ketan; Anbazhagan, P.
2018-01-01
Advancement in the seismic networks results in formulation of different functional forms for developing any new ground motion prediction equation (GMPE) for a region. Till date, various guidelines and tools are available for selecting a suitable GMPE for any seismic study area. However, these methods are efficient in quantifying the GMPE but not for determining a proper functional form and capturing the epistemic uncertainty associated with selection of GMPE. In this study, the compatibility of the recent available functional forms for the active region is tested for distance and magnitude scaling. Analysis is carried out by determining the residuals using the recorded and the predicted spectral acceleration values at different periods. Mixed effect regressions are performed on the calculated residuals for determining the intra- and interevent residuals. Additionally, spatial correlation is used in mixed effect regression by changing its likelihood function. Distance scaling and magnitude scaling are respectively examined by studying the trends of intraevent residuals with distance and the trend of the event term with magnitude. Further, these trends are statistically studied for a respective functional form of a ground motion. Additionally, genetic algorithm and Monte Carlo method are used respectively for calculating the hinge point and standard error for magnitude and distance scaling for a newly determined functional form. The whole procedure is applied and tested for the available strong motion data for the Himalayan region. The functional form used for testing are five Himalayan GMPEs, five GMPEs developed under NGA-West 2 project, two from Pan-European, and one from Japan region. It is observed that bilinear functional form with magnitude and distance hinged at 6.5 M w and 300 km respectively is suitable for the Himalayan region. Finally, a new regression coefficient for peak ground acceleration for a suitable functional form that governs the attenuation characteristic of the Himalayan region is derived.
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Subduction hinge migration: The backwards component of plate tectonics
NASA Astrophysics Data System (ADS)
Stegman, D.; Freeman, J.; Schellart, W.; Moresi, L.; May, D.
2005-12-01
There are approximately 50 distinct segments of subduction zones in the world, of which 40% have oceanic lithosphere subducting under oceanic lithosphere. All of these ocean-ocean systems are currently experiencing hinge-rollback, with the exception of 2 (Mariana and Kermadec). In hinge-rollback, the surface trace of the suduction zone (trench) is moving in the opposite direction as the plate is moving (i.e. backwards). Coincidentally, the fastest moving plate boundary in the world is actually the Tonga trench at an estimated 17 cm/yr (backwards). Although this quite important process was recognized soon after the birth of plate tectonic theory (Elsasser, 1971), it has received only a limited amount of attention (Garfunkel, 1986; Kincaid and Olson, 1987) until recently. Laboratory models have shown that having a three dimensional experiment is essential in order to build a correct understanding of subduction. We have developed a numerical model with the neccessary 3-D geometry capable of investigating some fundamental questions of plate tectonics: How does hinge-rollback feedback into surface tectonics and mantle flow? What can we learn about the forces that drive plate tectonics by studying hinge-rollback? We will present a quantatitive analysis of the effect of the lateral width of subduction zones, the key aspect to understanding the nature of hinge-rollback. Additionally, particular emphasis has been put on gaining intuition through the use of movies (a 3-D rendering of the numerical models), illustrating the time evolution of slab interactions with the lower mantle as seen in such fields as velocity magnitude, strain rate, viscosity, as well as the toroidal and poloidal components of induced flow. This investigation is well-suited to developing direct comparisons with geological and geophysical observations such as geodetically determined hinge retreat rates, geochemical and petrological observations of arc volcanics and back-arc ridge basalts, timing and distribution of metamorphic core complexes in backarc basins under extension, paleostress observables such surface movements and block rotations, observations of seismic anistropy determined by shear wave splitting, and the emerging studies of regional tomographic models of seismic anistropy.
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Bukiya, Anna N; Rosenhouse-Dantsker, Avia
2017-07-01
G-protein gated inwardly rectifying potassium (GIRK or Kir3) channels play a major role in the control of the heart rate, and require the membrane phospholipid phosphatidylinositol-bis-phosphate (PI(4,5)P 2 ) for activation. Recently, we have shown that the activity of the heterotetrameric Kir3.1/Kir3.4 channel that underlies atrial K ACh currents was enhanced by cholesterol. Similarly, the activities of both the Kir3.4 homomer and its active pore mutant Kir3.4* (Kir3.4_S143T) were also enhanced by cholesterol. Here we employ planar lipid bilayers to investigate the crosstalk between PI(4,5)P 2 and cholesterol, and demonstrate that these two lipids act synergistically to activate Kir3.4* currents. Further studies using the Xenopus oocytes heterologous expression system suggest that PI(4,5)P 2 and cholesterol act via distinct binding sites. Whereas PI(4,5)P 2 binds to the cytosolic domain of the channel, the putative binding region of cholesterol is located at the center of the transmembrane domain overlapping the central glycine hinge region of the channel. Together, our data suggest that changes in the levels of two key membrane lipids - cholesterol and PI(4,5)P 2 - could act in concert to provide fine-tuning of Kir3 channel function. Copyright © 2017 Elsevier B.V. All rights reserved.
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Approximate method for calculating a thickwalled cylinder with rigidly clamped ends
NASA Astrophysics Data System (ADS)
Andreev, Vladimir
2018-03-01
Numerous papers dealing with the calculations of cylindrical bodies [1 -8 and others] have shown that analytic and numerical-analytical solutions in both homogeneous and inhomogeneous thick-walled shells can be obtained quite simply, using expansions in Fourier series on trigonometric functions, if the ends are hinged movable (sliding support). It is much more difficult to solve the problem of calculating shells with builtin ends.
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Rigid collapsible dish structure
NASA Technical Reports Server (NTRS)
Palmer, William B. (Inventor); Giebler, Martin M. (Inventor)
1982-01-01
A collapsible dish structure composed of a plurality of rows of rigid radial petal assemblies concentric with the axis of the dish. The petal assemblies consist of a center petal and two side petals, the center petal hinged on an axis tangent to a circle concentric with the axis of the dish and the side petals hinged to the center petal at their mating edge. The center petal is foldable inwardly and the side petals rotate about their hinges such that the collapsed dish structure occupies a much smaller volume than the deployed dish. Means of controlling the shape of the dish to compensate for differential expansion of the deployed dish are also provided.
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DETAIL VIEW OF WINCH USED TO RAISE AND LOWER HINGED ...
DETAIL VIEW OF WINCH USED TO RAISE AND LOWER HINGED SECTION OF THIRD FLOOR LEVEL, PLATFORM D-SOUTH, HB-3, FACING WEST - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL
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78 FR 15281 - Airworthiness Directives; The Boeing Company Airplanes
Federal Register 2010, 2011, 2012, 2013, 2014
2013-03-11
... horizontal stabilizer. This AD requires repetitive high frequency eddy current (HFEC) inspections for... repetitive high frequency eddy current (HFEC) inspections for cracking of the left and right rib hinge... high frequency eddy current (HFEC) inspection for cracking of the left and right rib hinge bearing lugs...
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Cold argon-oxygen plasma species oxidize and disintegrate capsid protein of feline calicivirus
Mor, Sunil K.; Higgins, LeeAnn; Armien, Anibal; Youssef, Mohammed M.; Bruggeman, Peter J.; Goyal, Sagar M.
2018-01-01
Possible mechanisms that lead to inactivation of feline calicivirus (FCV) by cold atmospheric-pressure plasma (CAP) generated in 99% argon-1% O2 admixture were studied. We evaluated the impact of CAP exposure on the FCV viral capsid protein and RNA employing several cultural, molecular, proteomic and morphologic characteristics techniques. In the case of long exposure (2 min) to CAP, the reactive species of CAP strongly oxidized the major domains of the viral capsid protein (VP1) leading to disintegration of a majority of viral capsids. In the case of short exposure (15 s), some of the virus particles retained their capsid structure undamaged but failed to infect the host cells in vitro. In the latter virus particles, CAP exposure led to the oxidation of specific amino acids located in functional peptide residues in the P2 subdomain of the protrusion (P) domain, the dimeric interface region of VP1 dimers, and the movable hinge region linking the S and P domains. These regions of the capsid are known to play an essential role in the attachment and entry of the virus to the host cell. These observations suggest that the oxidative effect of CAP species inactivates the virus by hindering virus attachment and entry into the host cell. Furthermore, we found that the oxidative impact of plasma species led to oxidation and damage of viral RNA once it becomes unpacked due to capsid destruction. The latter effect most likely plays a secondary role in virus inactivation since the intact FCV genome is infectious even after damage to the capsid. PMID:29566061
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NASA Astrophysics Data System (ADS)
Nymeyer, Hugh; Socci, Nicholas D.; Onuchic, José Nelson
2000-01-01
* Department of Physics, University of California at San Diego, La Jolla, CA 92093-0319; and § Center for Studies in Physics and Biology, The Rockefeller University, New York, NY 10021 Edited by R. Stephen Berry, University of Chicago, Chicago, IL, and approved November 5, 1999 (received for review July 2, 1999) We present a method for determining structural properties of the ensemble of folding transition states from protein simulations. This method relies on thermodynamic quantities (free energies as a function of global reaction coordinates, such as the percentage of native contacts) and not on "kinetic" measurements (rates, transmission coefficients, complete trajectories); consequently, it requires fewer computational resources compared with otherapproaches, making it more suited to large and complex models. We explain the theoretical framework that underlies this method and use it to clarify the connection between the experimentally determined
value, a quantity determined by the ratio of rate and stability changes due to point mutations, and the average structure of the transition state ensemble. To determine the accuracy of this thermodynamic approach, we apply it to minimalist protein models and compare these results with the ones obtained by using the standard experimental procedure for determining values. We show that the accuracy of both methods depends sensitively on the amount of frustration. In particular, the results are similar when applied to models with minimal amounts of frustration, characteristic of rapid-folding, single-domain globular proteins. -
Park, Jong-Tae; Lee, Jae-Gi; Won, Sung-Yoon; Lee, Sang-Hee; Cha, Jung-Yul; Kim, Hee-Jin
2013-07-01
Masticatory muscles are closely involved in mastication, pronunciation, and swallowing, and it is therefore important to study the specific functions and dynamics of the mandibular and masticatory muscles. However, the shortness of muscle fibers and the diversity of movement directions make it difficult to study and simplify the dynamics of mastication. The purpose of this study was to use 3-dimensional (3D) simulation to observe the functions and movements of each of the masticatory muscles and the mandible while chewing. To simulate the masticatory movement, computed tomographic images were taken from a single Korean volunteer (30-year-old man), and skull image data were reconstructed in 3D (Mimics; Materialise, Leuven, Belgium). The 3D-reconstructed masticatory muscles were then attached to the 3D skull model. The masticatory movements were animated using Maya (Autodesk, San Rafael, CA) based on the mandibular motion path. During unilateral chewing, the mandible was found to move laterally toward the functional side by contracting the contralateral lateral pterygoid and ipsilateral temporalis muscles. During the initial mouth opening, only hinge movement was observed at the temporomandibular joint. During this period, the entire mandible rotated approximately 13 degrees toward the bicondylar horizontal plane. Continued movement of the mandible to full mouth opening occurred simultaneously with sliding and hinge movements, and the mandible rotated approximately 17 degrees toward the center of the mandibular ramus. The described approach can yield data for use in face animation and other simulation systems and for elucidating the functional components related to contraction and relaxation of muscles during mastication.
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Hinge specification for a square-faceted tetrahedral truss
NASA Technical Reports Server (NTRS)
Adams, L. R.
1984-01-01
A square-faceted tetrahedral truss is geometrically analyzed. Expressions are developed for single degree of freedom hinges which allow packaging of the structure into a configuration in which all members are parallel and closely packed in a square pattern. Deployment is sequential, thus providing control over the structure during deployment.
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NASA Technical Reports Server (NTRS)
Death, M. D.
1984-01-01
The evolution of an Antenna Deployment Mechanism (ADM) from a Hinge Actuator Mechanism (HAM) is described as it pertains to the deployment of large satellite antennas. Design analysis and mechanical tests are examined in detail.
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78 FR 24985 - Airworthiness Directives; Cessna Aircraft Company Airplanes
Federal Register 2010, 2011, 2012, 2013, 2014
2013-04-29
... (L-126A,B,C), 195A, and 195B airplanes that are equipped with certain inboard aileron hinge brackets... 4, 2013), currently requires you to repetitively inspect the affected inboard aileron hinge brackets... brackets. Replacement with aluminum brackets would terminate the need for the repetitive inspections...
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14 CFR 23.393 - Loads parallel to hinge line.
Code of Federal Regulations, 2011 CFR
2011-01-01
...) K=24 for vertical surfaces; (2) K=12 for horizontal surfaces; and (3) W=weight of the movable... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Loads parallel to hinge line. 23.393 Section 23.393 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION...
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14 CFR 23.393 - Loads parallel to hinge line.
Code of Federal Regulations, 2013 CFR
2013-01-01
...) K=24 for vertical surfaces; (2) K=12 for horizontal surfaces; and (3) W=weight of the movable... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Loads parallel to hinge line. 23.393 Section 23.393 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION...
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14 CFR 23.393 - Loads parallel to hinge line.
Code of Federal Regulations, 2014 CFR
2014-01-01
...) K=24 for vertical surfaces; (2) K=12 for horizontal surfaces; and (3) W=weight of the movable... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Loads parallel to hinge line. 23.393 Section 23.393 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION...
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14 CFR 23.393 - Loads parallel to hinge line.
Code of Federal Regulations, 2012 CFR
2012-01-01
...) K=24 for vertical surfaces; (2) K=12 for horizontal surfaces; and (3) W=weight of the movable... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Loads parallel to hinge line. 23.393 Section 23.393 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION...
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14 CFR 23.393 - Loads parallel to hinge line.
Code of Federal Regulations, 2010 CFR
2010-01-01
...) K=24 for vertical surfaces; (2) K=12 for horizontal surfaces; and (3) W=weight of the movable... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Loads parallel to hinge line. 23.393 Section 23.393 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION...
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49 CFR 571.224 - Standard No. 224; Rear impact protection.
Code of Federal Regulations, 2011 CFR
2011-10-01
... the vehicle is in motion. Nonstructural protrusions such as taillights, rubber bumpers, hinges and... deliver asphalt and other road building materials, in a controlled horizontal manner, into a lay down... protrusions such as taillights, hinges, rubber bumpers, and latches are excluded from the determination of the...
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61. DETAIL OF HEAD, VANE STEM, VANE HINGE, AND WHEEL ...
61. DETAIL OF HEAD, VANE STEM, VANE HINGE, AND WHEEL OF AN ELI WINDMILL ON THE GROUND AT THE STOLL RESIDENCE ABOUT 1-1/2 MILES WEST OF NEBRASKA CITY ON STEAM WAGON ROAD. - Kregel Windmill Company Factory, 1416 Central Avenue, Nebraska City, Otoe County, NE
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Angular motion equations for a satellite with hinged flexible solar panel
NASA Astrophysics Data System (ADS)
Ovchinnikov, M. Yu.; Tkachev, S. S.; Roldugin, D. S.; Nuralieva, A. B.; Mashtakov, Y. V.
2016-11-01
Non-linear mathematical model for the satellite with hinged flexible solar panel is presented. Normal modes of flexible elements are used for motion description. Motion equations are derived using virtual work principle. A comparison of normal modes calculation between finite element method and developed model is presented.
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[COSMOS motion design optimization in the CT table].
Shang, Hong; Huang, Jian; Ren, Chao
2013-03-01
Through the CT Table dynamic simulation by COSMOS Motion, analysis the hinge of table and the motor force, then optimize the position of the hinge of table, provide the evidence of selecting bearing and motor, meanwhile enhance the design quality of the CT table and reduce the product design cost.
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Bogucki, Artur J
2014-01-01
The knee joint is a bicondylar hinge two-level joint with six degrees of freedom. The location of the functional axis of flexion-extension motion is still a subject of research and discussions. During the swing phase, the femoral condyles do not have direct contact with the tibial articular surfaces and the intra-articular space narrows with increasing weight bearing. The geometry of knee movements is determined by the shape of articular surfaces. A digital recording of the gait of a healthy volunteer was analysed. In the first experimental variant, the subject was wearing a knee orthosis controlling flexion and extension with a hinge-type single-axis joint. In the second variant, the examination involved a hinge-type double-axis orthosis. Statistical analysis involved mathematically calculated values of displacement P. Scatter graphs with a fourth-order polynomial trend line with a confidence interval of 0.95 due to noise were prepared for each experimental variant. In Variant 1, the average displacement was 15.1 mm, the number of tests was 43, standard deviation was 8.761, and the confidence interval was 2.2. The maximum value of displacement was 30.9 mm and the minimum value was 0.7 mm. In Variant 2, the average displacement was 13.4 mm, the number of tests was 44, standard deviation was 7.275, and the confidence interval was 1.8. The maximum value of displacement was 30.2 mm and the minimum value was 3.4 mm. An analysis of moving averages for both experimental variants revealed that displacement trends for both types of orthosis were compatible from the mid-stance to the mid-swing phase. 1. The method employed in the experiment allows for determining the alignment between the axis of the knee joint and that of shin and thigh orthoses. 2. Migration of the single and double-axis orthoses during the gait cycle exceeded 3 cm. 3. During weight bearing, the double-axis orthosis was positioned more correctly. 4. The study results may be helpful in designing new hinge-type knee joints.
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Design of a single-chain polypeptide tetrahedron assembled from coiled-coil segments.
Gradišar, Helena; Božič, Sabina; Doles, Tibor; Vengust, Damjan; Hafner-Bratkovič, Iva; Mertelj, Alenka; Webb, Ben; Šali, Andrej; Klavžar, Sandi; Jerala, Roman
2013-06-01
Protein structures evolved through a complex interplay of cooperative interactions, and it is still very challenging to design new protein folds de novo. Here we present a strategy to design self-assembling polypeptide nanostructured polyhedra based on modularization using orthogonal dimerizing segments. We designed and experimentally demonstrated the formation of the tetrahedron that self-assembles from a single polypeptide chain comprising 12 concatenated coiled coil-forming segments separated by flexible peptide hinges. The path of the polypeptide chain is guided by a defined order of segments that traverse each of the six edges of the tetrahedron exactly twice, forming coiled-coil dimers with their corresponding partners. The coincidence of the polypeptide termini in the same vertex is demonstrated by reconstituting a split fluorescent protein in the polypeptide with the correct tetrahedral topology. Polypeptides with a deleted or scrambled segment order fail to self-assemble correctly. This design platform provides a foundation for constructing new topological polypeptide folds based on the set of orthogonal interacting polypeptide segments.
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Signal transduction in light–oxygen–voltage receptors lacking the adduct-forming cysteine residue
Yee, Estella F.; Diensthuber, Ralph P.; Vaidya, Anand T.; Borbat, Peter P.; Engelhard, Christopher; Freed, Jack H.; Bittl, Robert; Möglich, Andreas; Crane, Brian R.
2015-01-01
Light–oxygen–voltage (LOV) receptors sense blue light through the photochemical generation of a covalent adduct between a flavin-nucleotide chromophore and a strictly conserved cysteine residue. Here we show that, after cysteine removal, the circadian-clock LOV-protein Vivid still undergoes light-induced dimerization and signalling because of flavin photoreduction to the neutral semiquinone (NSQ). Similarly, photoreduction of the engineered LOV histidine kinase YF1 to the NSQ modulates activity and downstream effects on gene expression. Signal transduction in both proteins hence hinges on flavin protonation, which is common to both the cysteinyl adduct and the NSQ. This general mechanism is also conserved by natural cysteine-less, LOV-like regulators that respond to chemical or photoreduction of their flavin cofactors. As LOV proteins can react to light even when devoid of the adduct-forming cysteine, modern LOV photoreceptors may have arisen from ancestral redox-active flavoproteins. The ability to tune LOV reactivity through photoreduction may have important implications for LOV mechanism and optogenetic applications. PMID:26648256
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NASA Technical Reports Server (NTRS)
Lindsey, A. I.; Milam, M. D.
1974-01-01
Aerodynamic investigations were conducted in a transonic pressure tunnel on an 0.015 scale model of the space shuttle orbiter. Major test objectives were to determine: (1) transonic differential elevon/aileron lateral control optimization; (2) transonic elevon hinge moments; (3) transonic effects of the baseline 6 inch elevon/elevon and elevon/fuselage gaps; and (4) transonic effects of the short OMS pods. Six-component aerodynamic force and moment, and elevon hinge moment data, were recorded over an angle-of-attack range form -2 to +22 degrees.
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Abraham, Anup; Chandler, Douglas E
2017-10-01
Proteins of the CAP superfamily play numerous roles in reproduction, innate immune responses, cancer biology, and venom toxicology. Here we document the breadth of the CAP (Cysteine-RIch Secretory Protein (CRISP), Antigen 5, and Pathogenesis-Related) protein superfamily and trace the major events in its evolution using amino acid sequence homology and the positions of exon/intron borders within their genes. Seldom acknowledged in the literature, we find that many of the CAP subfamilies present in mammals, where they were originally characterized, have distinct homologues in the invertebrate phyla. Early eukaryotic CAP genes contained only one exon inherited from prokaryotic predecessors and as evolution progressed an increasing number of introns were inserted, reaching 2-5 in the invertebrate world and 5-15 in the vertebrate world. Focusing on the CRISP subfamily, we propose that these proteins evolved in three major steps: (1) origination of the CAP/PR/SCP domain in bacteria, (2) addition of a small Hinge domain to produce the two-domain SCP-like proteins found in roundworms and anthropoids, and (3) addition of an Ion Channel Regulatory domain, borrowed from invertebrate peptide toxins, to produce full length, three-domain CRISP proteins, first seen in insects and later to diversify into multiple subtypes in the vertebrate world.
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Effect of hinge-moment parameters on elevator stick forces in rapid maneuvers
NASA Technical Reports Server (NTRS)
Jones, Robert T; Greenberg, Harry
1944-01-01
The importance of the stick force per unit normal acceleration as a criterion of longitudinal stability and the critical dependence of this gradient on elevator hinge-moment parameters have been shown in previous reports. The present report continues the investigation with special reference to transient effects for maneuvers of short duration.
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Deployable video conference table
NASA Technical Reports Server (NTRS)
Cohen, Marc M. (Inventor); Lissol, Peter (Inventor)
1993-01-01
A deployable table is presented. The table is stowed in and deployed from a storage compartment based upon a non-self rigidizing, 4-hinge, arch support structure that folds upon itself to stow and that expands to deploy. The work surfaces bypass each other above and below to allow the deployment mechanism to operate. This assembly includes the following: first and second primary pivot hinges placed at the opposite ends of the storage compartment; first and second lateral frame members with proximal ends connected to the first and second pivot hinges; a medial frame member offset from and pivotally connected to distal ends of the first and second members through third and fourth medial pivot hinges; and left-side, right-side, and middle trays connected respectively to the first, second, and third frame members and being foldable into and out of the storage compartment by articulation of the first, second, third, and fourth joints. At least one of the third and fourth joints are locked to set the first, second, and third frame members in a desired angular orientation with respect to each other.
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Operational characterization of CSFH MEMS technology based hinges
NASA Astrophysics Data System (ADS)
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.
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Anterior knee symptoms after S-ROM hinge implantation.
Deehan, David J; Gangadharan, Rajkumar; Malviya, Ajay; Sutherland, Alasdair; Holland, James P
2014-01-01
To evaluate the performance of a canal filling hinge device for complex knee arthroplasty. Thirty-seven (4 primary hinge implantation and 33 revision cases) patients who had undergone arthroplasty with the S-ROM third generation hinge device for a combination of massive bone loss or ligamentous insufficiency were prospectively examined with a minimum of 5-year follow-up. Median age at surgery was 72 years (range: 43 to 87 years). Principal indications included aseptic loosening or massive osteolysis (24 cases), infection (8 cases) and periprosthetic fracture (4 cases). All patients exhibited either grade 2 (N = 12) or grade 3 (N = 25) AORI bone loss or a grade 3 medial ligament deficiency. One patient experienced implant failure (71 months), and one patient suffered late deep infection (36 months). Mean WOMAC score improved from 27 to 62. Four patients required patellar resurfacing for persistent pain. The 5-year survivorship was 86%. While the S-ROM device may offer satisfactory medium term outcome for complex end stage knee disease, we report a high rate of debilitating anterior knee symptoms.
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English, Charles A; Sherman, Woody; Meng, Wenli; Gierasch, Lila M
2017-09-08
Hsp70 molecular chaperones play key roles in cellular protein homeostasis by binding to exposed hydrophobic regions of incompletely folded or aggregated proteins. This crucial Hsp70 function relies on allosteric communication between two well-structured domains: an N-terminal nucleotide-binding domain (NBD) and a C-terminal substrate-binding domain (SBD), which are tethered by an interdomain linker. ATP or ADP binding to the NBD alters the substrate-binding affinity of the SBD, triggering functionally essential cycles of substrate binding and release. The interdomain linker is a well-structured participant in the interdomain interface in ATP-bound Hsp70s. By contrast, in the ADP-bound state, exemplified by the Escherichia coli Hsp70 DnaK, the interdomain linker is flexible. Hsp70 interdomain linker sequences are highly conserved; moreover, mutations in this region compromise interdomain allostery. To better understand the role of this region in Hsp70 allostery, we used molecular dynamics simulations to explore the conformational landscape of the interdomain linker in ADP-bound DnaK and supported our simulations by strategic experimental data. We found that while the interdomain linker samples many conformations, it behaves as three relatively ordered segments connected by hinges. As a consequence, the distances and orientations between the NBD and SBD are limited. Additionally, the C-terminal region of the linker forms previously unreported, transient interactions with the SBD, and the predominant linker-docking site is available in only one allosteric state, that with high affinity for substrate. This preferential binding implicates the interdomain linker as a dynamic allosteric switch. The linker-binding site on the SBD is a potential target for small molecule modulators of the Hsp70 allosteric cycle. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.
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Mascarenhas, Nahren Manuel; Kästner, Johannes
2013-02-01
A well-studied periplasmic-binding protein involved in the abstraction of maltose is maltose-binding protein (MBP), which undergoes a ligand-induced conformational transition from an open (ligand-free) to a closed (ligand-bound) state. Umbrella sampling simulations have been us to estimate the free energy of binding of maltose to MBP and to trace the potential of mean force of the unbinding event using the center-of-mass distance between the protein and ligand as the reaction coordinate. The free energy thus obtained compares nicely with the experimentally measured value justifying our theoretical basis. Measurement of the domain angle (N-terminal-domain - hinge - C-terminal-domain) along the unbinding pathway established the existence of three different states. Starting from a closed state, the protein shifts to an open conformation during the initial unbinding event of the ligand then resides in a semi-open conformation and later resides predominantly in an open-state. These transitions along the ligand unbinding pathway have been captured in greater depth using principal component analysis. It is proposed that in mixed-model, both conformational selection and an induced-fit mechanism combine to the ligand recognition process in MBP. Copyright © 2012 Wiley Periodicals, Inc.
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NASA Technical Reports Server (NTRS)
McCarty, John Locke; Brooks, George W.; Maglieri, Domenic J.
1959-01-01
A two-blade rotor having a diameter of 4 feet and a solidity of 0.037 was tested in the Langley 300-MPH 7- by 10-foot tunnel to obtain information on the effect of certain rotor variables on the blade periodic bending moments and flapping angles during the various stages of transformation between the helicopter and autogiro configuration. Variables studied included collective pitch angle, flapping-hinge offset, rotor angle of attack, and tip-speed ratio. The results show that the blade periodic bending moments generally increase with tip-speed ratio up into the transition region, diminish over a certain range of tip-speed ratio, and increase again at higher tip-speed ratios. Above the transition region, the bending moments increase with collective pitch angle and rotor angle of attack. The absence of a flapping hinge results in a significant amplification of the periodic bending moments, the magnitudes of which increase with tip-speed ratio. When the flapping hinge is used, an increase in flapping-hinge offset results in reduced period bending moments. The aforementioned trends exhibited by the bending moments for changes in the variables are essentially duplicated by the periodic flapping motions. The existence of substantial amounts of blade stall increased both the periodic bending moments and the flapping angles. Harmonic analysis of the bending moments shows significant contributions of the higher harmonics, particularly in the transition region.
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Comparison of platelet activation through hinge vs bulk flow in mechanical heart valves
NASA Astrophysics Data System (ADS)
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.
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Investigation of the effect of physical parameters on the design of tumour targeting agents
NASA Astrophysics Data System (ADS)
Casey, Joanne Lois
Tumour targeting using radiolabelled antibodies for radioimmunodetection (RAID) and radioimmunotherapy (RIT) has been studied for many years. The main factors that have limited clinical success are low tumour uptake, immunogenicity and poor therapeutic ratios. This thesis has applied current technology to make advances in this area of research. The effect of physical parameters (antibody size, valency, affinity and charge) on the design of tumour targeting agents was studied by constructing divalent (DFM) and trivalent (TFM) forms of the murine anti-CEA antibody A5B7 Fab' by chemical cross-linking. This involves partial reduction of the hinge disulphides to expose thiol (-SH) groups and subsequent reaction with a maleimide cross-linker to form a thioether bond at the hinge region. Previous studies have suggested that the stability of thioether bonds is superior to naturally occurring disulphide bonds present at the hinge region of IgG and F(ab')2. The aim was to compare the functional affinities and in vivo tumour targeting in nude mice bearing human tumour xenografts of DFM and TFM to similar sized parent IgG and F(ab')2. Radiolabelling with 131I and 90Y was also compared with a view to determine which combination would be optimal for RIT. Results clearly demonstrated a significantly faster on-rate of DFM compared to all other antibody forms and estimated dosimetry analysis suggested that DFM would be the most suitable antibody form radiolabelled with 131I for RIT. Both F(ab')2 and DFM showed high kidney uptake levels on labelling with which is unacceptable for RIT. Despite the improved tumour: blood ratios for TFM, the increased estimated dose to normal tissues and lower therapeutic effect in RIT studies suggests that the most promising combination with the radionuclide appears to be IgG. A humanised version of A5B7 hFab' has been constructed previously in order to reduce its immunogenicity in man. The in vivo stability of hDFM proved to be superior to hF(ab')2 in the nude mouse xenograft model. To study the safety, stability and tumour targeting of hDFM a clinical trial using 131I was described here including details of production, characterisation, pharmacokinetics and dosimetry. ScFv's are known to have favourable tumour targeting characteristics compared to whole antibodies for RAID. To evaluate the clinical potential of a scFv, the methodology to prepare a phage derived scFv with the aid of a subcloned hexahistidine tail was described here. To enhance the clinical potential of scFv's a construct consisting of a hinge region containing a single cysteine residue was constructed. This enabled site-specific 99mTc-labelling and could facilitate multimerisation. One of the major limitations revealed by this and other studies is the problem associated with renal accretion of antibody fragments. Various modification techniques and blocking effects were used here in attempt to reduce the kidney uptake levels in mouse models. Reduction of the pi of A5B7 Fab by attachment of NHS-ester groups was effective in lowering kidney uptake levels, but losses in immunoreactivity could limit this approach. Attachment of PEG (5kD) to DFM did not adversely affect immunoreactivity and increased the circulation time of DFM in vivo. This has implications for reducing kidney uptake levels at early time points, in addition PEG is known to reduce immunogenicity of proteins.
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Klem, Nardia-Rose; Wild, Catherine Y; Williams, Sian A; Ng, Leo
2017-03-01
Despite the high prevalence of lower extremity injuries in female basketball players as well as a high proportion of athletes who wear ankle braces, there is a paucity of research pertaining to the effects of ankle bracing on ankle and knee biomechanics during basketball-specific tasks. To compare the effects of a lace-up brace (ASO), a hinged brace (Active T2), and no ankle bracing (control) on ankle and knee joint kinematics and joint reaction forces in female basketball athletes during a cutting maneuver. Controlled laboratory study. Twenty healthy, semi-elite female basketball players performed a cutting task under both ankle brace conditions (lace-up ankle brace and hinged ankle brace) and a no-brace condition. The 3-dimensional kinematics of the ankle and knee during the cutting maneuver were measured with an 18-camera motion analysis system (250 Hz), and ground-reaction force data were collected by use of a multichannel force plate (2000 Hz) to quantify ankle and knee joint reaction forces. Conditions were randomized using a block randomization method. Compared with the control condition, the hinged ankle brace significantly restricted peak ankle inversion (mean difference, 1.7°; P = .023). No significant difference was found between the lace-up brace and the control condition ( P = .865). Compared with the lace-up brace, the hinged brace significantly reduced ankle and knee joint compressive forces at the time of peak ankle dorsiflexion (mean difference, 1.5 N/kg [ P = .018] and 1.4 N/kg [ P = .013], respectively). Additionally, the hinged ankle brace significantly reduced knee anterior shear forces compared with the lace-up brace both during the deceleration phase and at peak ankle dorsiflexion (mean difference, 0.8 N/kg [ P = .018] and 0.9 N/kg [ P = .011], respectively). The hinged ankle brace significantly reduced ankle inversion compared with the no-brace condition and reduced ankle and knee joint forces compared with the lace-up brace in a female basketball population during a cutting task. Compared with the lace-up brace, the hinged brace may be a better choice of prophylactic ankle support for female basketball players from a biomechanical perspective. However, both braces increased knee internal rotation and knee abduction angles, which may be problematic for a population that already has a high prevalence of knee injuries.
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Zargarian, Loussiné; Tisné, Carine; Barraud, Pierre; Xu, Xiaoqian; Morellet, Nelly; René, Brigitte; Mély, Yves; Fossé, Philippe; Mauffret, Olivier
2014-01-01
The HIV-1 nucleocapsid protein (NC) is a small basic protein containing two zinc fingers (ZF) separated by a short linker. It is involved in several steps of the replication cycle and acts as a nucleic acid chaperone protein in facilitating nucleic acid strand transfers occurring during reverse transcription. Recent analysis of three-dimensional structures of NC-nucleic acids complexes established a new property: the unpaired guanines targeted by NC are more often inserted in the C-terminal zinc finger (ZF2) than in the N-terminal zinc finger (ZF1). Although previous NMR dynamic studies were performed with NC, the dynamic behavior of the linker residues connecting the two ZF domains remains unclear. This prompted us to investigate the dynamic behavior of the linker residues. Here, we collected 15N NMR relaxation data and used for the first time data at several fields to probe the protein dynamics. The analysis at two fields allows us to detect a slow motion occurring between the two domains around a hinge located in the linker at the G35 position. However, the amplitude of motion appears limited in our conditions. In addition, we showed that the neighboring linker residues R29, A30, P31, R32, K33 displayed restricted motion and numerous contacts with residues of ZF1. Our results are fully consistent with a model in which the ZF1-linker contacts prevent the ZF1 domain to interact with unpaired guanines, whereas the ZF2 domain is more accessible and competent to interact with unpaired guanines. In contrast, ZF1 with its large hydrophobic plateau is able to destabilize the double-stranded regions adjacent to the guanines bound by ZF2. The linker residues and the internal dynamics of NC regulate therefore the different functions of the two zinc fingers that are required for an optimal chaperone activity.
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Zargarian, Loussiné; Tisné, Carine; Barraud, Pierre; Xu, Xiaoqian; Morellet, Nelly; René, Brigitte; Mély, Yves; Fossé, Philippe; Mauffret, Olivier
2014-01-01
The HIV-1 nucleocapsid protein (NC) is a small basic protein containing two zinc fingers (ZF) separated by a short linker. It is involved in several steps of the replication cycle and acts as a nucleic acid chaperone protein in facilitating nucleic acid strand transfers occurring during reverse transcription. Recent analysis of three-dimensional structures of NC-nucleic acids complexes established a new property: the unpaired guanines targeted by NC are more often inserted in the C-terminal zinc finger (ZF2) than in the N-terminal zinc finger (ZF1). Although previous NMR dynamic studies were performed with NC, the dynamic behavior of the linker residues connecting the two ZF domains remains unclear. This prompted us to investigate the dynamic behavior of the linker residues. Here, we collected 15N NMR relaxation data and used for the first time data at several fields to probe the protein dynamics. The analysis at two fields allows us to detect a slow motion occurring between the two domains around a hinge located in the linker at the G35 position. However, the amplitude of motion appears limited in our conditions. In addition, we showed that the neighboring linker residues R29, A30, P31, R32, K33 displayed restricted motion and numerous contacts with residues of ZF1. Our results are fully consistent with a model in which the ZF1-linker contacts prevent the ZF1 domain to interact with unpaired guanines, whereas the ZF2 domain is more accessible and competent to interact with unpaired guanines. In contrast, ZF1 with its large hydrophobic plateau is able to destabilize the double-stranded regions adjacent to the guanines bound by ZF2. The linker residues and the internal dynamics of NC regulate therefore the different functions of the two zinc fingers that are required for an optimal chaperone activity. PMID:25029439
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Protein promiscuity: drug resistance and native functions--HIV-1 case.
Fernández, Ariel; Tawfik, Dan S; Berkhout, Ben; Sanders, Rogier; Kloczkowski, Andrzej; Sen, Taner; Jernigan, Bob
2005-06-01
The association of a drug with its target protein has the effect of blocking the protein activity and is termed a promiscuous function to distinguish from the protein's native function (Tawfik and associates, Nat. Genet. 37, 73-6, 2005). Obviously, a protein has not evolved naturally for drug association or drug resistance. Promiscuous protein functions exhibit unique traits of evolutionary adaptability, or evolvability, which is dependent on the induction of novel phenotypic traits by a small number of mutations. These mutations might have small effects on native functions, but large effects on promiscuous function; for example, an evolving protein could become increasingly drug resistant while maintaining its original function. Ariel Fernandez, in his opinion piece, notes that drug-binding "promiscuity" can hardly be dissociated from native functions; a dominant approach to drug discovery is the protein-native-substrate transition-state mimetic strategy. Thus, man-made ligands (e.g. drugs) have been successfully crafted to restrain enzymatic activity by focusing on the very same structural features that determine the native function. Using the successful inhibition of HIV-1 protease as an example, Fernandez illustrates how drug designers have employed naturally evolved features of the protein to suppress its activity. Based on these arguments, he dismisses the notion that drug binding is quintessentially promiscuous, even though in principle, proteins did not evolve to associate with man made ligands. In short, Fernandez argues that there may not be separate protein domains that one could term promiscuous domains. While acknowledging that drugs may bind promiscuously or in a native-like manner a la Fernandez, Tawfik maintains the role of evolutionary adaptation, even when a drug binds native-like. In the case of HIV-1 protease, drugs bind natively, and the initial onset of mutations results in drug resistance in addition to a dramatic decline in enzymatic activity and fitness of the virus. A chain of compensatory mutations follows this, and then the virus becomes fully fit and drug resistant. Ben Berkhout and Rogier Sanders subscribe to the evolution of new protein functions through gene duplication. With two identical protein domains, one domain can be released from a constraint imposed by the original function and it is thus free to move in sequence space toward a new function without loss of the original function. They emphasize that the forced evolution of drug-resistance differs significantly from the spontaneous evolution of an additional protein function. For instance, the latter process could proceed gradually on an evolutionary time scale, whereas the acquisition of drug-resistance is an all or nothing process for a virus, leading to the failure or success of therapy. They find no evidence to the thesis that resistance-mutations appear more rapidly in promiscuous domains than native domains. Berkhout and Sanders illustrate the genetic plasticity of HIV-1 by citing examples in which well-conserved amino acid residues of catalytic domains are forced to mutate under drug-pressure. HIV drug resistance biology is very complex. Instead of a viral protein, a drug can be targeted at a cellular protein. For example, Berkhout and Sanders claim, a drug targeted at the cellular protein CCR5 inhibits the binding of the viral envelope glycoprotein (Env) to CCR5. However, Env mutates so that it binds to the CCR5-drug complex and develops drug resistance. Interestingly, CCR5 has not evolved to bind to Env, but to a series of chemokines. Andrzej Kloczkowski, Taner Sen, and Bob Jernigan point out the importance of protein motions for binding. They believe it is likely that different ligands can bind to the diverse protein conformations sampled in the course of normal protein conformational fluctuations. They have been applying simple elastic network models to extract the motions as normal modes, which yield relatively small numbers of conformations that are useful for developing protein mechanisms; while these are typically small motions, for some proteins they can be quite large in scale. One of the major advantages of the approach is that only relatively small numbers of modes are important contributors to the overall motion -- so the approach provides a way to systematically map out a protein's motions. These models successfully represent the conformational fluctuations manifested in the crystallographic B-factors, and often suggest motions related to protein functional behaviors, such as those observed for reverse transcriptase, where two dominant hinges clearly relate to the processing steps -- one showing anti-correlation between the polymerase and ribonuclease H sites related to the translation and positioning of the nucleic acid chain, and another for opening and closing the polymerase site. Disordered proteins represent a more extreme case where the set of accessible conformations is much larger; thus they could offer up a broader range of possible binding forms. Whether evolution controls the functional motions for proteins remains little studied. Intriguingly, buried in the existing databases of protein-protein interactions may be information that can shed light on the extent of promiscuous binding among proteins themselves. Within these data there are cases where large numbers of diverse proteins have been shown to interact with a single protein; some of these could represent promiscuous protein-protein binding. Uncovering these promiscuous behaviors could be important for comprehending the details of how proteins can bind promiscuously to one another, and can exhibit even greater promiscuity in their binding to small molecules. The evolutionary routes, the dynamics of the target protein, and the many other aspects that need to be addressed while designing a drug that may dodge drug resistance, indicate the complexity and multi-disciplinary nature of the issue of drug resistance.
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Bispecific Anti-HIV-1 Antibodies with Enhanced Breadth and Potency.
Bournazos, Stylianos; Gazumyan, Anna; Seaman, Michael S; Nussenzweig, Michel C; Ravetch, Jeffrey V
2016-06-16
Broadly neutralizing antibodies (bNAbs) against the HIV-1 envelope glycoprotein (Env) suppress viremia in animal models of HIV-1 and humans. To achieve potent activity without the emergence of viral escape mutants, co-administration of different bNAbs is necessary to target distinct epitopes essential for viral fitness. Here, we report the development of bispecific anti-Env neutralizing antibodies (biNAbs) with potent activity. Synergistic activity of biNAbs was achieved by combining an engineered hinge domain of IgG3 to increase Fab domain flexibility necessary for hetero-bivalent binding to the Env trimer while retaining the functional properties of the IgG1-Fc. Compared to unmodified biNAbs, hinge domain variants exhibited substantially improved neutralization activity, with particular combinations showing evidence of synergistic neutralization potency in vitro and enhanced in vivo therapeutic activity in HIV-1-infected humanized mice. These findings suggest innovative strategies for generating biNAbs with enhanced neutralization breadth and potency, representing ideal candidate molecules for the control of HIV-1 infection. Copyright © 2016 Elsevier Inc. All rights reserved.
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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 program. This shows that DCPs carry strong potential to deliver evidence-based, cost-effective care to those suffering from CKP. PMID:28582253
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77 FR 20515 - Airworthiness Directives; Airbus Airplanes
Federal Register 2010, 2011, 2012, 2013, 2014
2012-04-05
... attachment fittings and the swan neck with serviceable ones if necessary. This AD was prompted by reports of cracks on the forward attachment fittings of the left and right sides of the forward hinge of the nose... (FWD) fittings (hinge 5) of the NLG aft doors (Right Hand (RH) side or Left Hand (LH) side). The cracks...
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75 FR 22543 - Airworthiness Directives; Aircraft Industries a.s. Model L 23 Super Blanik Gliders
Federal Register 2010, 2011, 2012, 2013, 2014
2010-04-29
... unsafe condition as: Cracks on the stabilizer elevator inner hinges of seven L 23 SUPERBLAN[Iacute]K... the need for the immediate inspection of the elevator inner hinges on the stabilizer. The European Aviation Safety Agency (EASA), which is the Technical Agent for the Member States of the European Community...
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75 FR 17295 - Airworthiness Directives; Aircraft Industries a.s. Model L 23 Super Blanik Gliders
Federal Register 2010, 2011, 2012, 2013, 2014
2010-04-06
... elevator inner hinges of seven L 23 SUPERBLAN[Iacute]K sailplanes have been detected during an inspection... European Aviation Safety Agency (EASA), which is the Technical Agent for the Member States of the European... stabilizer elevator inner hinges of seven L 23 SUPERBLAN[Iacute]K sailplanes have been detected during an...
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NASA Technical Reports Server (NTRS)
Esparza, V.
1975-01-01
Experimental aerodynamic investigations were conducted in the Arnold Engineering Development Center (AEDC) Von Karman Facility Tunnel A on a scale model of the space shuttle orbiter. The objectives of this test were: (1) determine supersonic differential elevon/aileron lateral control optimization, (2) determine supersonic elevon hinge moments, (3) determine the supersonic effects of the new baseline 6-inch elevon/elevon and elevon/fuselage gaps, and 4) determine the supersonic effects of the new short (VL70-008410) OMS pods. Six-component aerodynamic force, moment, and elevon hinge moment data were recorded.
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Wind-Tunnel Investigation of the Effect of Tab Balance on Tab and Control-Surface Characteristics
NASA Technical Reports Server (NTRS)
Brewer, Jack D; Queijo, M J
1947-01-01
An investigation was conducted to furnish data on the effect of tab balance on tab and control-surface characteristics. The airfoil tested had a modified NACA 65(1)-012 contour with a plain flap having a chord equal to 25 percent of the wing chord and with a tab having a chord equal to 25 percent of the flap chord and having several nose shapes and overhang lengths. The results of the investigation indicated that, in general, tab balance affected tab hinge-moment characteristics in much the same manner that flap balance affects flap hinge-moment characteristics. A moderate amount of tab balance did not seem to have any adverse effect on flap hinge-moment characteristics.
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Apparatus for raising or tilting a micromechanical structure
Allen, James J [Albuquerque, NM
2008-09-09
An active hinge apparatus is disclosed which can be used to raise a micromechanical structure (e.g. a plate or micromirror) on a substrate. The active hinge apparatus utilizes one or more of teeth protruding outward from an axle which also supports the micromechanical structure on one end thereof. A rack is used to engage the teeth and rotate the axle to raise the micromechanical structure and tilt the structure at an angle to the substrate. Motion of the rack is provided by an actuator which can be a mechanically-powered actuator, or alternately an electrostatic comb actuator or a thermal actuator. A latch can be optionally provided in the active hinge apparatus to lock the micromechanical structure in an "erected" position.
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Structural basis for the facilitative diffusion mechanism by SemiSWEET transporter
NASA Astrophysics Data System (ADS)
Lee, Yongchan; Nishizawa, Tomohiro; Yamashita, Keitaro; Ishitani, Ryuichiro; Nureki, Osamu
2015-01-01
SWEET family proteins mediate sugar transport across biological membranes and play crucial roles in plants and animals. The SWEETs and their bacterial homologues, the SemiSWEETs, are related to the PQ-loop family, which is characterized by highly conserved proline and glutamine residues (PQ-loop motif). Although the structures of the bacterial SemiSWEETs were recently reported, the conformational transition and the significance of the conserved motif in the transport cycle have remained elusive. Here we report crystal structures of SemiSWEET from Escherichia coli, in the both inward-open and outward-open states. A structural comparison revealed that SemiSWEET undergoes an intramolecular conformational change in each protomer. The conserved PQ-loop motif serves as a molecular hinge that enables the ‘binder clip-like’ motion of SemiSWEET. The present work provides the framework for understanding the overall transport cycles of SWEET and PQ-loop family proteins.
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Mechanical properties of nanostructure of biological materials
NASA Astrophysics Data System (ADS)
Ji, Baohua; Gao, Huajian
2004-09-01
Natural biological materials such as bone, teeth and nacre are nanocomposites of protein and mineral with superior strength. It is quite a marvel that nature produces hard and tough materials out of protein as soft as human skin and mineral as brittle as classroom chalk. What are the secrets of nature? Can we learn from this to produce bio-inspired materials in the laboratory? These questions have motivated us to investigate the mechanics of protein-mineral nanocomposite structure. Large aspect ratios and a staggered alignment of mineral platelets are found to be the key factors contributing to the large stiffness of biomaterials. A tension-shear chain (TSC) model of biological nanostructure reveals that the strength of biomaterials hinges upon optimizing the tensile strength of the mineral crystals. As the size of the mineral crystals is reduced to nanoscale, they become insensitive to flaws with strength approaching the theoretical strength of atomic bonds. The optimized tensile strength of mineral crystals thus allows a large amount of fracture energy to be dissipated in protein via shear deformation and consequently enhances the fracture toughness of biocomposites. We derive viscoelastic properties of the protein-mineral nanostructure and show that the toughness of biocomposite can be further enhanced by the viscoelastic properties of protein.
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Free energy calculations of glycosaminoglycan-protein interactions.
Gandhi, Neha S; Mancera, Ricardo L
2009-10-01
Glycosaminoglycans (GAGs) are complex highly charged linear polysaccharides that have a variety of roles in biological processes. We report the first use of molecular dynamics (MD) free energy calculations using the MM/PBSA method to investigate the binding of GAGs to protein molecules, namely the platelet endothelial cell adhesion molecule 1 (PECAM-1) and annexin A2. Calculations of the free energy of the binding of heparin fragments of different sizes reveal the existence of a region of low GAG-binding affinity in domains 5-6 of PECAM-1 and a region of high affinity in domains 2-3, consistent with experimental data and ligand-protein docking studies. A conformational hinge movement between domains 2 and 3 was observed, which allows the binding of heparin fragments of increasing size (pentasaccharides to octasaccharides) with an increasingly higher binding affinity. Similar simulations of the binding of a heparin fragment to annexin A2 reveal the optimization of electrostatic and hydrogen bonding interactions with the protein and protein-bound calcium ions. In general, these free energy calculations reveal that the binding of heparin to protein surfaces is dominated by strong electrostatic interactions for longer fragments, with equally important contributions from van der Waals interactions and vibrational entropy changes, against a large unfavorable desolvation penalty due to the high charge density of these molecules.
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Small-angle neutron scattering study of a monoclonal antibody using free-energy constraints.
Clark, Nicholas J; Zhang, Hailiang; Krueger, Susan; Lee, Hyo Jin; Ketchem, Randal R; Kerwin, Bruce; Kanapuram, Sekhar R; Treuheit, Michael J; McAuley, Arnold; Curtis, Joseph E
2013-11-14
Monoclonal antibodies (mAbs) contain hinge-like regions that enable structural flexibility of globular domains that have a direct effect on biological function. A subclass of mAbs, IgG2, have several interchain disulfide bonds in the hinge region that could potentially limit structural flexibility of the globular domains and affect the overall configuration space available to the mAb. We have characterized human IgG2 mAb in solution via small-angle neutron scattering (SANS) and interpreted the scattering data using atomistic models. Molecular Monte Carlo combined with molecular dynamics simulations of a model mAb indicate that a wide range of structural configurations are plausible, spanning radius of gyration values from ∼39 to ∼55 Å. Structural ensembles and representative single structure solutions were derived by comparison of theoretical SANS profiles of mAb models to experimental SANS data. Additionally, molecular mechanical and solvation free-energy calculations were carried out on the ensemble of best-fitting mAb structures. The results of this study indicate that low-resolution techniques like small-angle scattering combined with atomistic molecular simulations with free-energy analysis may be helpful to determine the types of intramolecular interactions that influence function and could lead to deleterious changes to mAb structure. This methodology will be useful to analyze small-angle scattering data of many macromolecular systems.
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Getting to the meat of the matter: beyond protein supplementation in maintenance dialysis.
Bailey, James L; Franch, Harold A
2009-01-01
Until recently, patients on dialysis with low serum albumin levels were characterized as suffering from protein malnutrition suggesting that the cause of this malady was due to an inadequate intake of protein. In fact, these patients tend to suffer from a wasting syndrome similar to cachexia commonly associated with inflammation in which there is loss of lean body mass and fat mass is underutilized. The term protein energy wasting has been used to characterize this syndrome and suggests that the simple addition of protein supplements to the dietary regimen of hemodialysis patients will not cure this malady. Correction of the underlying inflammatory disorder which drives losses of body protein and fuel reserves is far more important and is the single most effective therapy. Protein supplements which may promote albumin synthesis and synthesis of liver-related proteins tend to increase muscle catabolism. Muscle growth is not fostered by increasing dietary protein above recommended goals for dialysis patients, but can be promoted by the addition of protein of high biological value that is rich in leucine and other essential amino acids in tandem with repetitive exercises. Ultimately, correction of PEW hinges on the diagnosis and treatment of co-morbid conditions in combination with strategies to replenish caloric and protein stores. A supplementary exercise program would allow recovery of lean body mass. Given the multiple co-morbidities that exist in this population, therapy would have to be individualized.
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Folding Polyominoes from One Level to Two
ERIC Educational Resources Information Center
Frederickson, Greg N.
2011-01-01
For any given polyomino, is it possible to cut it into pieces and then hinge the pieces, so that the polyomino folds up into a similar version of itself but two levels thick? While we don't know how to do this for every polyomino, the article does show how to cut, hinge, and fold polyominoes from several infinite classes, providing an…
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49 CFR 571.206 - Standard No. 206; Door locks and door retention components.
Code of Federal Regulations, 2012 CFR
2012-10-01
... (GVWR) of 4,536 kg or less. S3. Definitions. Auxiliary Door Latch is a latch equipped with a fully... auxiliary door latch on each hinged door shall not disengage from the fully latched position when an inertia... hinged back door shall also not disengage from the fully latched position when an inertia load is applied...
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49 CFR 571.206 - Standard No. 206; Door locks and door retention components.
Code of Federal Regulations, 2013 CFR
2013-10-01
... (GVWR) of 4,536 kg or less. S3. Definitions. Auxiliary Door Latch is a latch equipped with a fully... auxiliary door latch on each hinged door shall not disengage from the fully latched position when an inertia... hinged back door shall also not disengage from the fully latched position when an inertia load is applied...
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49 CFR 571.206 - Standard No. 206; Door locks and door retention components.
Code of Federal Regulations, 2011 CFR
2011-10-01
... (GVWR) of 4,536 kg or less. S3. Definitions. Auxiliary Door Latch is a latch equipped with a fully... auxiliary door latch on each hinged door shall not disengage from the fully latched position when an inertia... hinged back door shall also not disengage from the fully latched position when an inertia load is applied...
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49 CFR 571.206 - Standard No. 206; Door locks and door retention components.
Code of Federal Regulations, 2014 CFR
2014-10-01
... (GVWR) of 4,536 kg or less. S3. Definitions. Auxiliary Door Latch is a latch equipped with a fully... auxiliary door latch on each hinged door shall not disengage from the fully latched position when an inertia... hinged back door shall also not disengage from the fully latched position when an inertia load is applied...
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NASA Astrophysics Data System (ADS)
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.
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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.
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NASA Technical Reports Server (NTRS)
Murray, Harry E.; Erwin, Mary A.
1945-01-01
The results of a theoretical analysis of the hinge-moment characteristics of various sealed-internal-balance arrangements for control surfaces are presented. The analysis considered overhands sealed to various types of wing structure by flexible seals spanning gaps of various widths or sealed to the wing structure by a flexible system of linked plates. Leakage was not considered; the seal was assumed to extend the full spanwise length of the control surface. The effect of the developed width of the flexible seal and of the geometry of the structure to which the seal was anchored was investigated, as well as the effect of the gap width that is sealed. The results of the investigation indicated that the most nearly linear control-surface hinge-moment characteristics can probably be obtained from a flexible seal over a narrow gap (about 0.1 of the overhang chord), which is so installed that the motion of the seal is restricted to a region behind the point of attachment of the seal to the wing structure. Control-surface hinge moments that tend to be high at large deflections and low or overbalanced at small deflections will result if a very narrow seal is used.
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Flectofold—a biomimetic compliant shading device for complex free form facades
NASA Astrophysics Data System (ADS)
Körner, A.; Born, L.; Mader, A.; Sachse, R.; Saffarian, S.; Westermeier, A. S.; Poppinga, S.; Bischoff, M.; Gresser, G. T.; Milwich, M.; Speck, T.; Knippers, J.
2018-01-01
Smart and adaptive outer façade shading systems are of high interest in modern architecture. For long lasting and reliable systems, the abandonment of hinges which often fail due to mechanical wear during repetitive use is of particular importance. Drawing inspiration from the hinge-less motion of the underwater snap-trap of the carnivorous waterwheel plant (Aldrovanda vesiculosa), the compliant façade shading device Flectofold was developed. Based on computational simulations of the biological role-model’s elastic and reversible motion, the actuation principle of the plant can be identified. The enclosed geometric motion principle is abstracted into a simplified curved-line folding geometry with distinct flexible hinge-zones. The kinematic behaviour is translated into a quantitative kinetic model, using finite element simulation which allows the detailed analyses of the influence of geometric parameters such as curved-fold line radius and various pneumatically driven actuation principles on the motion behaviour, stress concentrations within the hinge-zones, and actuation forces. The information regarding geometric relations and material gradients gained from those computational models are then used to develop novel material combinations for glass fibre reinforced plastics which enabled the fabrication of physical prototypes of the compliant façade shading device Flectofold.
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Elasto-Capillary Folding Using Stop-Programmable Hinges Fabricated by 3D Micro-Machining
Legrain, Antoine; Berenschot, Erwin J. W.; Tas, Niels R.; Abelmann, Leon
2015-01-01
We show elasto-capillary folding of silicon nitride objects with accurate folding angles between flaps of (70.6 ± 0.1)° and demonstrate the feasibility of such accurate micro-assembly with a final folding angle of 90°. The folding angle is defined by stop-programmable hinges that are fabricated starting from silicon molds employing accurate three-dimensional corner lithography. This nano-patterning method exploits the conformal deposition and the subsequent timed isotropic etching of a thin film in a 3D shaped silicon template. The technique leaves a residue of the thin film in sharp concave corners which can be used as an inversion mask in subsequent steps. Hinges designed to stop the folding at 70.6° were fabricated batchwise by machining the V-grooves obtained by KOH etching in (110) silicon wafers; 90° stop-programmable hinges were obtained starting from silicon molds obtained by dry etching on (100) wafers. The presented technique has potential to achieve any folding angle and opens a new route towards creating structures with increased complexity, which will ultimately lead to a novel method for device fabrication. PMID:25992886
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NASA Astrophysics Data System (ADS)
Tan, Chee Ghuan; Chia, Wei Ting; Majid, Taksiah A.; Nazri, Fadzli Mohamed; Adiyanto, Mohd Irwan
2017-10-01
On 5th June 2015, a moderate earthquake with Mw 5.9 hit Ranau, resulted in damages of the existing non-seismically designed buildings, such that 61 buildings, including mosques, schools, hospitals and Ranau police headquarters were suffered from different level structural damages. Soft storey irregularity is one of the main reasons of the building damage. This study is to investigate the soft-story effect on the propagation path of plastic hinges RC building under seismic excitation. The plastic hinges formation and seismic performance of five moment resisting RC frames with different infill configurations are studied. The seismic performance of building is evaluated by Incremental Dynamic Analysis (IDA). Open ground soft storey structure shows the lowest seismic resistance, collapses at 0.55g pga. The maximum interstorey drift ratio (IDRmax) in soft storey buildings ranging from 0.53% to 2.96% which are far greater than bare frame ranging from 0.095% to 0.69%. The presence of infill walls creates stiffer upper stories causing moments concentrate at the soft storey, resulting the path of plastic hinge propagation is dominant at the soft storey columns. Hence, the buildings with soft storey are very susceptible under earthquake load.
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Structural insight into recruitment of translesion DNA polymerase Dpo4 to sliding clamp PCNA
DOE Office of Scientific and Technical Information (OSTI.GOV)
Xing, G.; Kirouac, K.; Shin, Y.J.
2009-09-16
DNA polymerases are co-ordinated by sliding clamps (PCNA/{beta}-clamp) in translesion synthesis. It is unclear how these enzymes assemble on PCNA with geometric and functional compatibility. We report the crystal structure of a full-length Y-family polymerase, Dpo4, in complex with heterodimeric PCNA1-PCNA2 at 2.05 {angstrom} resolution. Dpo4 exhibits an extended conformation that differs from the Dpo4 structures in apo- or DNA-bound form. Two hinges have been identified in Dpo4, which render the multidomain polymerase flexible conformations and orientations relative to PCNA. Dpo4 binds specifically to PCNA1 on the conserved ligand binding site. The C-terminal peptide of Dpo4 becomes structured with amore » 3{sub 10} helix and dominates the specific binding. The Y-family polymerase also contacts PCNA1 with its finger, thumb and little finger domains, which are conformation-dependent protein-protein interactions that diversify the binding mode of Dpo4 on PCNA. The structure reveals a molecular model in which substrate/partner binding-coupled multiple conformations of a Y-family polymerase facilitate its recruitment and co-ordination on the sliding clamp. The conformational flexibility would turn the error-prone Y-family polymerase off when more efficient high-fidelity DNA polymerases work on undamaged DNA and turn it onto DNA templates to perform translesion synthesis when replication forks are stalled by DNA lesions.« less
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Wang, Zhiming; Qiao, Zhu; Ye, Sheng; Zhang, Rongguang
2015-04-01
Tandem duplications and fusions of single genes have led to magnificent expansions in the divergence of protein structures and functions over evolutionary timescales. One of the possible results is polydomain enzymes with interdomain cooperativities, few examples of which have been structurally characterized at the full-length level to explore their innate synergistic mechanisms. This work reports the crystal structures of a double-domain phosphagen kinase in both apo and ligand-bound states, revealing a novel asymmetric L-shaped arrangement of the two domains. Unexpectedly, the interdomain connections are not based on a flexible hinge linker but on a rigid secondary-structure element: a long α-helix that tethers the tandem domains in relatively fixed positions. Besides the connective helix, the two domains also contact each other directly and form an interdomain interface in which hydrogen bonds and hydrophobic interactions further stabilize the L-shaped domain arrangement. Molecular-dynamics simulations show that the interface is generally stable, suggesting that the asymmetric domain arrangement crystallographically observed in the present study is not a conformational state simply restrained by crystal-packing forces. It is possible that the asymmetrically arranged tandem domains could provide a structural basis for further studies of the interdomain synergy.
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Karasawa, Akira; Erkens, Guus B.; Berntsson, Ronnie P.-A.; Otten, Renee; Schuurman-Wolters, Gea K.; Mulder, Frans A. A.; Poolman, Bert
2011-01-01
The cystathionine β-synthase module of OpuA in conjunction with an anionic membrane surface acts as a sensor of internal ionic strength, which allows the protein to respond to osmotic stress. We now show by chemical modification and cross-linking studies that CBS2-CBS2 interface residues are critical for transport activity and/or ionic regulation of transport, whereas CBS1 serves no functional role. We establish that Cys residues in CBS1, CBS2, and the nucleotide-binding domain are more accessible for cross-linking at high than low ionic strength, indicating that these domains undergo conformational changes when transiting between the active and inactive state. Structural analyses suggest that the cystathionine β-synthase module is largely unstructured. Moreover, we could substitute CBS1 by a linker and preserve ionic regulation of transport. These data suggest that CBS1 serves as a linker and the structured CBS2-CBS2 interface forms a hinge point for ionic strength-dependent rearrangements that are transmitted to the nucleotide-binding domain and thereby affect translocation activity. PMID:21878634
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2012-01-01
Mutations in the LRRK2 gene are the most common cause of genetic Parkinson’s disease. Although the mechanisms behind the pathogenic effects of LRRK2 mutations are still not clear, data emerging from in vitro and in vivo models suggests roles in regulating neuronal polarity, neurotransmission, membrane and cytoskeletal dynamics and protein degradation. We created mice lacking exon 41 that encodes the activation hinge of the kinase domain of LRRK2. We have performed a comprehensive analysis of these mice up to 20 months of age, including evaluation of dopamine storage, release, uptake and synthesis, behavioral testing, dendritic spine and proliferation/neurogenesis analysis. Our results show that the dopaminergic system was not functionally comprised in LRRK2 knockout mice. However, LRRK2 knockout mice displayed abnormal exploratory activity in the open-field test. Moreover, LRRK2 knockout mice stayed longer than their wild type littermates on the accelerated rod during rotarod testing. Finally, we confirm that loss of LRRK2 caused degeneration in the kidney, accompanied by a progressive enhancement of autophagic activity and accumulation of autofluorescent material, but without evidence of biphasic changes. PMID:22647713
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Recent innovations in edible and/or biodegradable packaging materials.
Guilbert, S; Cuq, B; Gontard, N
1997-01-01
Certain newly discovered characteristics of natural biopolymers should make them a choice material to be used for different types of wrappings and films. Edible and/or biodegradable packagings produced from agricultural origin macromolecules provide a supplementary and sometimes essential means to control physiological, microbiological, and physicochemical changes in food products. This is accomplished (i) by controlling mass transfers between food product and ambient atmosphere or between components in heterogeneous food product, and (iii) by modifying and controlling food surface conditions (pH, level of specific functional agents, slow release of flavour compounds), it should be stressed that the material characteristics (polysaccharide, protein, or lipid, plasticized or not, chemically modified or not, used alone or in combination) and the fabrication procedures (casting of a film-forming solution, thermoforming) must be adapted to each specific food product and usage condition (relative humidity, temperature). Some potential uses of these materials (e.g. wrapping of various fabricated foods; protection of fruits and vegetables by control of maturation; protection of meat and fish; control of internal moisture transfer in pizzas), which are hinged on film properties (e.g. organoleptic, mechanical, gas and solute barrier) are described with examples.
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Enzyme cascades activated on topologically programmed DNA scaffolds
NASA Astrophysics Data System (ADS)
Wilner, Ofer I.; Weizmann, Yossi; Gill, Ron; Lioubashevski, Oleg; Freeman, Ronit; Willner, Itamar
2009-04-01
The ability of DNA to self-assemble into one-, two- and three-dimensional nanostructures, combined with the precision that is now possible when positioning nanoparticles or proteins on DNA scaffolds, provide a promising approach for the self-organization of composite nanostructures. Predicting and controlling the functions that emerge in self-organized biomolecular nanostructures is a major challenge in systems biology, and although a number of innovative examples have been reported, the emergent properties of systems in which enzymes are coupled together have not been fully explored. Here, we report the self-assembly of a DNA scaffold made of DNA strips that include `hinges' to which biomolecules can be tethered. We attach either two enzymes or a cofactor-enzyme pair to the scaffold, and show that enzyme cascades or cofactor-mediated biocatalysis can proceed effectively; similar processes are not observed in diffusion-controlled homogeneous mixtures of the same components. Furthermore, because the relative position of the two enzymes or the cofactor-enzyme pair is determined by the topology of the DNA scaffold, it is possible to control the reactivity of the system through the design of the individual DNA strips. This method could lead to the self-organization of complex multi-enzyme cascades.
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Meinhold, Derrick W.; Wright, Peter E.
2011-01-01
Detailed understanding of protein function and malfunction hinges on the ability to characterize transiently populated states and the transitions between them. Here, we use 15N, , and 13CO NMR R2 relaxation dispersion to investigate spontaneous unfolding and refolding events of native apomyoglobin. Above pH 5.0, dispersion is dominated by processes involving fluctuations of the F-helix region, which is invisible in NMR spectra. Measurements of R2 dispersion for residues contacted by the F-helix region in the native (N) structure reveal a transient state formed by local unfolding of helix F and undocking from the protein core. A similar state was detected at pH 4.75–4.95 and determined to be an on-pathway intermediate (I1) in a linear three-state unfolding scheme (N⇆I1⇆MG) leading to a transiently populated molten globule (MG) state. The slowest steps in unfolding and refolding are N → I1 (36 s-1) and MG → I1 (26 s-1), respectively. Differences in chemical shift between N and I1 are very small, except in regions adjacent to helix F, showing that their core structures are similar. Chemical shift changes between the N and MG states, obtained from R2 dispersion, reveal that the transient MG state is structurally similar to the equilibrium MG observed previously at high temperature and low pH. Analysis of MG state chemical shifts shows the location of residual helical structure in the transient intermediate and identifies regions that unfold or rearrange into nonnative structure during the N → MG transition. The experiments also identify regions of energetic frustration that “crack” during unfolding and impede the refolding process. PMID:21562212
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Insights into the Structural Dynamics of Nucleocytoplasmic Transport of tRNA by Exportin-t
Gupta, Asmita; Kailasam, Senthilkumar; Bansal, Manju
2016-01-01
Exportin-t (Xpot) transports mature 5′- and 3′-end processed tRNA from the nucleus to the cytoplasm by associating with a small G-protein Ran (RAs-related nuclear protein), in the nucleus. The release of tRNA in cytoplasm involves RanGTP hydrolysis. Despite the availability of crystal structures of nuclear and cytosolic forms of Xpot, the molecular details regarding the sequential events leading to tRNA release and subsequent conformational changes occurring in Xpot remain unknown. We have performed a combination of classical all-atom and accelerated molecular dynamics simulations on a set of complexes involving Xpot to study a range of features including conformational flexibility of free and cargo-bound Xpot and functionally critical contacts between Xpot and its cargo. The systems investigated include free Xpot and its different complexes, bound either to Ran (GTP/GDP) or tRNA or both. This approach provided a statistically reliable estimate of structural dynamics of Xpot after cargo release. The mechanistic basis for Xpot opening after cargo release has been explained in terms of dynamic structural hinges, about which neighboring region could be displaced to facilitate the nuclear to cytosolic state transition. Post-RanGTP hydrolysis, a cascade of events including local conformational change in RanGTP and loss of critical contacts at Xpot/tRNA interface suggest factors responsible for eventual release of tRNA. The level of flexibility in different Xpot complexes varied depending on the arrangement of individual HEAT repeats. Current study provides one of the most comprehensive and robust analysis carried out on this protein using molecular dynamics schemes. PMID:27028637
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Structure Refinement of Protein Low Resolution Models Using the GNEIMO Constrained Dynamics Method
Park, In-Hee; Gangupomu, Vamshi; Wagner, Jeffrey; Jain, Abhinandan; Vaidehi, Nagara-jan
2012-01-01
The challenge in protein structure prediction using homology modeling is the lack of reliable methods to refine the low resolution homology models. Unconstrained all-atom molecular dynamics (MD) does not serve well for structure refinement due to its limited conformational search. We have developed and tested the constrained MD method, based on the Generalized Newton-Euler Inverse Mass Operator (GNEIMO) algorithm for protein structure refinement. In this method, the high-frequency degrees of freedom are replaced with hard holonomic constraints and a protein is modeled as a collection of rigid body clusters connected by flexible torsional hinges. This allows larger integration time steps and enhances the conformational search space. In this work, we have demonstrated the use of a constraint free GNEIMO method for protein structure refinement that starts from low-resolution decoy sets derived from homology methods. In the eight proteins with three decoys for each, we observed an improvement of ~2 Å in the RMSD to the known experimental structures of these proteins. The GNEIMO method also showed enrichment in the population density of native-like conformations. In addition, we demonstrated structural refinement using a “Freeze and Thaw” clustering scheme with the GNEIMO framework as a viable tool for enhancing localized conformational search. We have derived a robust protocol based on the GNEIMO replica exchange method for protein structure refinement that can be readily extended to other proteins and possibly applicable for high throughput protein structure refinement. PMID:22260550
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Nawaz, Zarqa; Kakar, Kaleem Ullah; Saand, Mumtaz A; Shu, Qing-Yao
2014-10-04
Cyclic nucleotide-gated channels (CNGCs) are Ca2+-permeable cation transport channels, which are present in both animal and plant systems. They have been implicated in the uptake of both essential and toxic cations, Ca2+ signaling, pathogen defense, and thermotolerance in plants. To date there has not been a genome-wide overview of the CNGC gene family in any economically important crop, including rice (Oryza sativa L.). There is an urgent need for a thorough genome-wide analysis and experimental verification of this gene family in rice. In this study, a total of 16 full length rice CNGC genes distributed on chromosomes 1-6, 9 and 12, were identified by employing comprehensive bioinformatics analyses. Based on phylogeny, the family of OsCNGCs was classified into four major groups (I-IV) and two sub-groups (IV-A and IV- B). Likewise, the CNGCs from all plant lineages clustered into four groups (I-IV), where group II was conserved in all land plants. Gene duplication analysis revealed that both chromosomal segmentation (OsCNGC1 and 2, 10 and 11, 15 and 16) and tandem duplications (OsCNGC1 and 2) significantly contributed to the expansion of this gene family. Motif composition and protein sequence analysis revealed that the CNGC specific domain "cyclic nucleotide-binding domain (CNBD)" comprises a "phosphate binding cassette" (PBC) and a "hinge" region that is highly conserved among the OsCNGCs. In addition, OsCNGC proteins also contain various other functional motifs and post-translational modification sites. We successively built a stringent motif: (LI-X(2)-[GS]-X-[FV]-X-G-[1]-ELL-X-W-X(12,22)-SA-X(2)-T-X(7)-[EQ]-AF-X-L) that recognizes the rice CNGCs specifically. Prediction of cis-acting regulatory elements in 5' upstream sequences and expression analyses through quantitative qPCR demonstrated that OsCNGC genes were highly responsive to multiple stimuli including hormonal (abscisic acid, indoleacetic acid, kinetin and ethylene), biotic (Pseudomonas fuscovaginae and Xanthomonas oryzae pv. oryzae) and abiotic (cold) stress. There are 16 CNGC genes in rice, which were probably expanded through chromosomal segmentation and tandem duplications and comprise a PBC and a "hinge" region in the CNBD domain, featured by a stringent motif. The various cis-acting regulatory elements in the upstream sequences may be responsible for responding to multiple stimuli, including hormonal, biotic and abiotic stresses.
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Rhee, John M; Register, Bradley; Hamasaki, Takahiko; Franklin, Betty
2011-01-01
Prospective clinical series. To evaluate the ability of plate-only laminoplasty to achieve stable laminar arch reconstruction and to determine the rate and time course with which bony healing occurs in such constructs. Reconstruction of a stable laminar arch with sufficient room for the decompressed spinal cord is a desired goal when performing cervical laminoplasty for myelopathy. Traditional forms of laminoplasty fixation, such as sutures, bone struts, and ceramic spacers, may be associated with complications including loss of fixation, dislodgement with neurologic compromise, and premature laminoplasty closure. Plates, in contrast, provide more rigid fixation. Plate-only laminoplasty is gaining popularity as a method of laminoplasty fixation, but there is little data on its effectiveness. Fifty-four patients who underwent open door laminoplasty for cervical myelopathy and had available postoperative computed tomography (CT) scans formed the basis of this study. In all cases, a 4-mm round burr was used to create the hinge at the junction of the lateral mass and lamina by completely removing the dorsal cortex and thinning the ventral cortex until a greenstick deformation of the hinge could be produced. Laminoplasty plates were used as the sole method of fixation. No supplemental bone graft struts were used on the plated side, and the hinge side was not bone grafted. Axial CT scans obtained at 3, 6, and 12 months postoperatively were assessed for plate complications and bony healing of the hinge. No plate failures, dislodgements, or premature closures occurred in any of the levels at any time postoperatively. Computed tomography scan review demonstrated that 55% of levels were healed at 3 months, 77% at 6 months, and 93% at 12 months. At each timepoint, C6 and C7 had the highest hinge healing rates. Laminar screw backout was seen in 5/217 (2.3%) of levels, but was not associated with plate dislodgement, laminoplasty closure, or neurologic consequences, and did not occur in any case in which 2 laminar screws had been placed. Plate-only laminoplasty provided stable reconstruction of an expanded laminar arch with no failures, dislodgements, adverse neurologic consequences, or premature closures in 217 levels. Ninety-three percent of hinges demonstrated radiographic union at 12 months, and even those that did not heal by CT scan criteria maintained patent expansion of the spinal canal without adverse neurologic consequences. Supplemental bone graft does not appear necessary when plated laminoplasty is performed.
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2014-11-13
PIM kinases are not required for essential cellular functions . Furthermore, the presence of a unique hinge region in the ATP-binding site of PIM1...washing and blocking, cells were incubated with the appropriate primary antibodies overnight and incubated with fluorescent secondary antibodies...determined after 72 hrs of reverse transfection by using the CellTiter-Glo Luminescent cell viability assay and the results were normalized to RISC -free siRNA
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Domain motions of Argonaute, the catalytic engine of RNA interference
Ming, Dengming; Wall, Michael E; Sanbonmatsu, Kevin Y
2007-01-01
Background The Argonaute protein is the core component of the RNA-induced silencing complex, playing the central role of cleaving the mRNA target. Visual inspection of static crystal structures already has enabled researchers to suggest conformational changes of Argonaute that might occur during RNA interference. We have taken the next step by performing an all-atom normal mode analysis of the Pyrococcus furiosus and Aquifex aeolicus Argonaute crystal structures, allowing us to quantitatively assess the feasibility of these conformational changes. To perform the analysis, we begin with the energy-minimized X-ray structures. Normal modes are then calculated using an all-atom molecular mechanics force field. Results The analysis reveals low-frequency vibrations that facilitate the accommodation of RNA duplexes – an essential step in target recognition. The Pyrococcus furiosus and Aquifex aeolicus Argonaute proteins both exhibit low-frequency torsion and hinge motions; however, differences in the overall architecture of the proteins cause the detailed dynamics to be significantly different. Conclusion Overall, low-frequency vibrations of Argonaute are consistent with mechanisms within the current reaction cycle model for RNA interference. PMID:18053142
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Domain motions of Argonaute, the catalytic engine of RNA interference.
Ming, Dengming; Wall, Michael E; Sanbonmatsu, Kevin Y
2007-11-30
The Argonaute protein is the core component of the RNA-induced silencing complex, playing the central role of cleaving the mRNA target. Visual inspection of static crystal structures already has enabled researchers to suggest conformational changes of Argonaute that might occur during RNA interference. We have taken the next step by performing an all-atom normal mode analysis of the Pyrococcus furiosus and Aquifex aeolicus Argonaute crystal structures, allowing us to quantitatively assess the feasibility of these conformational changes. To perform the analysis, we begin with the energy-minimized X-ray structures. Normal modes are then calculated using an all-atom molecular mechanics force field. The analysis reveals low-frequency vibrations that facilitate the accommodation of RNA duplexes - an essential step in target recognition. The Pyrococcus furiosus and Aquifex aeolicus Argonaute proteins both exhibit low-frequency torsion and hinge motions; however, differences in the overall architecture of the proteins cause the detailed dynamics to be significantly different. Overall, low-frequency vibrations of Argonaute are consistent with mechanisms within the current reaction cycle model for RNA interference.
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Structure of the EMMPRIN N-terminal domain 1: Dimerization via [beta]-strand swapping
DOE Office of Scientific and Technical Information (OSTI.GOV)
Luo, Jinquan; Teplyakov, Alexey; Obmolova, Galina
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 (residuesmore » 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 ECD. Quite unexpectedly, ND1 forms a dimer mediated through the exchange of its last {beta}-strand (strand G). {beta}-strand swapping, which is a subset of 3D domain swapping, has been found to mediate cell-cell adhesion by cadherins. 3D domain swapping has been proposed to be a mechanism of protein oligomerization, aggregation, evolution of oligomeric proteins from single domains and amyloidogenesis. In domain swapped proteins, the same structural elements are involved in the final 3D structure, and so there is little overall energetic difference between the monomer and the swapped oligomers. However, there is often a high energy barrier for the conversion as it often goes through an unfolded state. It is also possible that strand-swapping occurs during folding of nascent polypeptide chains. Frequently, the exchange hinges contain proline-rich motifs which are often in high strain conformations. Domain swapping appears to be a strategy to resolve such local structural strain. The exchange hinge of ND1 contains a Pro-Glu-Pro tripeptide motif. Both of the proline residues adopt extended trans conformations, when compared with cis in the full-length ECD structure. Proline cis-trans isomerization may be the driving force for this exchange. Strand-exchanged dimerization may be a mechanism for the oligomerization of EMMPRIN ECD and its cis-dependent homophilic interactions in cell-cell adhesion.« less
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Attitude dynamics simulation subroutines for systems of hinge-connected rigid bodies
NASA Technical Reports Server (NTRS)
Fleischer, G. E.; Likins, P. W.
1974-01-01
Several computer subroutines are designed to provide the solution to minimum-dimension sets of discrete-coordinate equations of motion for systems consisting of an arbitrary number of hinge-connected rigid bodies assembled in a tree topology. In particular, these routines may be applied to: (1) the case of completely unrestricted hinge rotations, (2) the totally linearized case (all system rotations are small), and (3) the mixed, or partially linearized, case. The use of the programs in each case is demonstrated using a five-body spacecraft and attitude control system configuration. The ability of the subroutines to accommodate prescribed motions of system bodies is also demonstrated. Complete listings and user instructions are included for these routines (written in FORTRAN V) which are intended as multi- and general-purpose tools in the simulation of spacecraft and other complex electromechanical systems.
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Self-folding micropatterned polymeric containers.
Azam, Anum; Laflin, Kate E; Jamal, Mustapha; Fernandes, Rohan; Gracias, David H
2011-02-01
We demonstrate self-folding of precisely patterned, optically transparent, all-polymeric containers and describe their utility in mammalian cell and microorganism encapsulation and culture. The polyhedral containers, with SU-8 faces and biodegradable polycaprolactone (PCL) hinges, spontaneously assembled on heating. Self-folding was driven by a minimization of surface area of the liquefying PCL hinges within lithographically patterned two-dimensional (2D) templates. The strategy allowed for the fabrication of containers with variable polyhedral shapes, sizes and precisely defined porosities in all three dimensions. We provide proof-of-concept for the use of these polymeric containers as encapsulants for beads, chemicals, mammalian cells and bacteria. We also compare accelerated hinge degradation rates in alkaline solutions of varying pH. These optically transparent containers resemble three-dimensional (3D) micro-Petri dishes and can be utilized to sustain, monitor and deliver living biological components.
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Influence of tectonic folding on rockfall susceptibility, American Fork Canyon, Utah, USA
Coe, J.A.; Harp, E.L.
2007-01-01
We examine rockfall susceptibility of folded strata in the Sevier fold-thrust belt exposed in American Fork Canyon in north-central Utah. Large-scale geologic mapping, talus production data, rock-mass-quality measurements, and historical rockfall data indicate that rockfall susceptibility is correlated with limb dip and curvature of the folded, cliff-forming Mississippian limestones. On fold limbs, rockfall susceptibility increases as dip increases. This relation is controlled by several factors, including an increase in adverse dip conditions and apertures of discontinuities, and shearing by flexural slip during folding that has reduced the friction angles of discontinuities by smoothing surface asperities. Susceptibility is greater in fold hinge zones than on adjacent limbs primarily because there are greater numbers of discontinuities in hinge zones. We speculate that susceptibility increases in hinge zones as fold curvature becomes tighter.
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Tilting table for ergometer and for other biomedical devices
NASA Technical Reports Server (NTRS)
Gause, R. L.; Spier, R. A. (Inventor)
1973-01-01
The apparatus is for testing the human body in a variety of positions, ranging from the vertical to the supine, while exercising on an ergometer; and can also be used for angular positioning of other biomedical devices. It includes a floor plate and a hinged plate upon which to fix the ergometer, a back rest and a head rest attached at right angles to said hinged plate and behind the seat of the ergometer, dual hydraulic cylinders for raising and lowering the hinged plate through 90 deg by means of a self contained hydraulic system, with valve means for control and positive stops on the apparatus to prevent over travel. Tests can be made with the subject positioned on the seat of the ergometer, through the various angles, with a substantially normal body attitude relative to the seat and ergometer.
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Reconstruction of palatal defect using mucoperiosteal hinge flap and pushback palatoplasty.
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.
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Stetz, Gabrielle; Verkhivker, Gennady M.
2017-01-01
Allosteric interactions in the Hsp70 proteins are linked with their regulatory mechanisms and cellular functions. Despite significant progress in structural and functional characterization of the Hsp70 proteins fundamental questions concerning modularity of the allosteric interaction networks and hierarchy of signaling pathways in the Hsp70 chaperones remained largely unexplored and poorly understood. In this work, we proposed an integrated computational strategy that combined atomistic and coarse-grained simulations with coevolutionary analysis and network modeling of the residue interactions. A novel aspect of this work is the incorporation of dynamic residue correlations and coevolutionary residue dependencies in the construction of allosteric interaction networks and signaling pathways. We found that functional sites involved in allosteric regulation of Hsp70 may be characterized by structural stability, proximity to global hinge centers and local structural environment that is enriched by highly coevolving flexible residues. These specific characteristics may be necessary for regulation of allosteric structural transitions and could distinguish regulatory sites from nonfunctional conserved residues. The observed confluence of dynamics correlations and coevolutionary residue couplings with global networking features may determine modular organization of allosteric interactions and dictate localization of key mediating sites. Community analysis of the residue interaction networks revealed that concerted rearrangements of local interacting modules at the inter-domain interface may be responsible for global structural changes and a population shift in the DnaK chaperone. The inter-domain communities in the Hsp70 structures harbor the majority of regulatory residues involved in allosteric signaling, suggesting that these sites could be integral to the network organization and coordination of structural changes. Using a network-based formalism of allostery, we introduced a community-hopping model of allosteric communication. Atomistic reconstruction of signaling pathways in the DnaK structures captured a direction-specific mechanism and molecular details of signal transmission that are fully consistent with the mutagenesis experiments. The results of our study reconciled structural and functional experiments from a network-centric perspective by showing that global properties of the residue interaction networks and coevolutionary signatures may be linked with specificity and diversity of allosteric regulation mechanisms. PMID:28095400
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Stetz, Gabrielle; Verkhivker, Gennady M
2017-01-01
Allosteric interactions in the Hsp70 proteins are linked with their regulatory mechanisms and cellular functions. Despite significant progress in structural and functional characterization of the Hsp70 proteins fundamental questions concerning modularity of the allosteric interaction networks and hierarchy of signaling pathways in the Hsp70 chaperones remained largely unexplored and poorly understood. In this work, we proposed an integrated computational strategy that combined atomistic and coarse-grained simulations with coevolutionary analysis and network modeling of the residue interactions. A novel aspect of this work is the incorporation of dynamic residue correlations and coevolutionary residue dependencies in the construction of allosteric interaction networks and signaling pathways. We found that functional sites involved in allosteric regulation of Hsp70 may be characterized by structural stability, proximity to global hinge centers and local structural environment that is enriched by highly coevolving flexible residues. These specific characteristics may be necessary for regulation of allosteric structural transitions and could distinguish regulatory sites from nonfunctional conserved residues. The observed confluence of dynamics correlations and coevolutionary residue couplings with global networking features may determine modular organization of allosteric interactions and dictate localization of key mediating sites. Community analysis of the residue interaction networks revealed that concerted rearrangements of local interacting modules at the inter-domain interface may be responsible for global structural changes and a population shift in the DnaK chaperone. The inter-domain communities in the Hsp70 structures harbor the majority of regulatory residues involved in allosteric signaling, suggesting that these sites could be integral to the network organization and coordination of structural changes. Using a network-based formalism of allostery, we introduced a community-hopping model of allosteric communication. Atomistic reconstruction of signaling pathways in the DnaK structures captured a direction-specific mechanism and molecular details of signal transmission that are fully consistent with the mutagenesis experiments. The results of our study reconciled structural and functional experiments from a network-centric perspective by showing that global properties of the residue interaction networks and coevolutionary signatures may be linked with specificity and diversity of allosteric regulation mechanisms.
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NASA Astrophysics Data System (ADS)
Michalicek, M. Adrian; Bright, Victor M.
2001-10-01
This paper presents the design, fabrication, modeling, and testing of various arrays of cantilever micromirror devices integrated atop CMOS control electronics. The upper layers of the arrays are prefabricated in the MUMPs process and then flip-chip transferred to CMOS receiving modules using a novel latching off-chip hinge mechanism. This mechanism allows the micromirror arrays to be released, rotated off the edge of the host module and then bonded to the receiving module using a standard probe station. The hinge mechanism supports the arrays by tethers that are severed to free the arrays once bonded. The resulting devices are inherently planarized since the bottom of the first releasable MUMPs layer becomes the surface of the integrated mirror. The working devices are formed by mirror surfaces bonded to address electrodes fabricated above static memory cells on the CMOS module. These arrays demonstrate highly desirable features such as compatible address potentials, less than 2 nm of RMS roughness, approximately 1 micrometers of lateral position accuracy and the unique ability to metallize reflective surfaces without masking. Ultimately, the off-chip hinge mechanism enables very low-cost, simple, reliable, repeatable and accurate assembly of advanced MEMS and integrated microsystems without specialized equipment or complex procedures.
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NASA Technical Reports Server (NTRS)
Foley, Robert J.; Pendergraft, Odis C., Jr.
1991-01-01
A static (wind-off) test was conducted in the Static Test Facility of the 16-ft transonic tunnel to determine the performance and turning effectiveness of post-exit yaw vanes installed on two-dimensional convergent-divergent nozzles. One nozzle design that was previously tested was used as a baseline, simulating dry power and afterburning power nozzles at both 0 and 20 degree pitch vectoring conditions. Vanes were installed on these four nozzle configurations to study the effects of vane deflection angle, longitudinal and lateral location, size, and camber. All vanes were hinged at the nozzle sidewall exit, and in addition, some were also hinged at the vane quarter chord (double-hinged). The vane concepts tested generally produced yaw thrust vectoring angles much less than the geometric vane angles, for (up to 8 percent) resultant thrust losses. When the nozzles were pitch vectored, yawing effectiveness decreased as the vanes were moved downstream. Thrust penalties and yawing effectiveness both decreased rapidly as the vanes were moved outboard (laterally). Vane length and height changes increased yawing effectiveness and thrust ratio losses, while using vane camber, and double-hinged vanes increased resultant yaw angles by 50 to 100 percent.
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NASA Technical Reports Server (NTRS)
Olney, Candida D.; Hillebrandt, Heather; Reichenbach, Eric Y.
2000-01-01
A limited evaluation of the F/A-18 baseline loads model was performed on the Systems Research Aircraft at NASA Dryden Flight Research Center (Edwards, California). Boeing developed the F/A-18 loads model using a linear aeroelastic analysis in conjunction with a flight simulator to determine loads at discrete locations on the aircraft. This experiment was designed so that analysis of doublets could be used to establish aircraft aerodynamic and loads response at 20 flight conditions. Instrumentation on the right outboard leading edge flap, left aileron, and left stabilator measured the hinge moment so that comparisons could be made between in-flight-measured hinge moments and loads model-predicted values at these locations. Comparisons showed that the difference between the loads model-predicted and in-flight-measured hinge moments was up to 130 percent of the flight limit load. A stepwise regression technique was used to determine new loads derivatives. These derivatives were placed in the loads model, which reduced the error to within 10 percent of the flight limit load. This paper discusses the flight test methodology, a process for determining loads coefficients, and the direct comparisons of predicted and measured hinge moments and loads coefficients.
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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
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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.
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A proline-hinge alters the characteristics of the amphipathic α-helical AMPs.
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 <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 bound to DNA. These results indicate that the bending region of Anal 3- Pro peptide is prerequisite for effective antibiotic activity and may facilitate easy penetration of the lipid bilayers of the cell membrane.
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Knightsat Flight Design Review
2007-08-03
spring loaded hinges were obtained from McMaster under part number 15205A42. The fasteners used to attach each shutter to its corresponding hinge were... Coefficient of thermal expansion) is fairly well matched to the cell’s germanium substrate. Copper is not a good choice since it expands and contracts...Temperature: K Ground Station Transmission Line Temp.: 290 K Ground Station Sky Temperature: 450 K G.S. Transmission Line Coefficient : 0.7943 Ground Station
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NASA Technical Reports Server (NTRS)
Tang, M. H.; Sefic, W. J.; Sheldon, R. G.
1978-01-01
Concurrent strain gage and pressure transducer measured flight loads on a lifting reentry vehicle are compared and correlated with wind tunnel-predicted loads. Subsonic, transonic, and supersonic aerodynamic loads are presented for the left fin and control surfaces of the X-24B lifting reentry vehicle. Typical left fin pressure distributions are shown. The effects of variations in angle of attack, angle of sideslip, and Mach number on the left fin loads and rudder hinge moments are presented in coefficient form. Also presented are the effects of variations in angle of attack and Mach number on the upper flap, lower flap, and aileron hinge-moment coefficients. The effects of variations in lower flap hinge moments due to changes in lower flap deflection and Mach number are presented in terms of coefficient slopes.
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Coleman, Clint; Kurth, William T.
1994-06-14
A wind turbine has a rotor with at least one blade which has an aileron which is adjusted by an actuator. A hinge has two portions, one for mounting a stationary hinge arm to the blade, the other for coupling to the aileron actuator. Several types of hinges can be used, along with different actuators. The aileron is designed so that it has a constant chord with a number of identical sub-assemblies. The leading edge of the aileron has at least one curved portion so that the aileron does not vent over a certain range of angles, but vents if the position is outside the range. A cyclic actuator can be mounted to the aileron to adjust the position periodically. Generally, the aileron will be adjusted over a range related to the rotational position of the blade. A method for operating the cyclic assembly is also described.
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NASA Technical Reports Server (NTRS)
Nielsen, Jack N; Kaattari, George E; Drake, William C
1952-01-01
A simple method is presented for estimating lift, pitching-moment, and hinge-moment characteristics of all-movable wings in the presence of a body as well as the characteristics of wing-body combinations employing such wings. In general, good agreement between the method and experiment was obtained for the lift and pitching moment of the entire wing-body combination and for the lift of the wing in the presence of the body. The method is valid for moderate angles of attack, wing deflection angles, and width of gap between wing and body. The method of estimating hinge moment was not considered sufficiently accurate for triangular all-movable wings. An alternate procedure is proposed based on the experimental moment characteristics of the wing alone. Further theoretical and experimental work is required to substantiate fully the proposed procedure.
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Folding Elastic Thermal Surface - FETS
NASA Technical Reports Server (NTRS)
Urquiza, Eugenio; Zhang, Burt X.; Thelen, Michael P.; Rodriquez, Jose I.; Pellegrino, Sergio
2013-01-01
The FETS is a light and compact thermal surface (sun shade, IR thermal shield, cover, and/or deployable radiator) that is mounted on a set of offset tape-spring hinges. The thermal surface is constrained during launch and activated in space by a thermomechanical latch such as a wax actuator. An application-specific embodiment of this technology developed for the MATMOS (Mars Atmospheric Trace Molecule Occultation Spectrometer) project serves as a deployable cover and thermal shield for its passive cooler. The FETS fits compactly against the instrument within the constrained launch envelope, and then unfolds into a larger area once in space. In this application, the FETS protects the passive cooler from thermal damage and contamination during ground operations, launch, and during orbit insertion. Once unfolded or deployed, the FETS serves as a heat shield, intercepting parasitic heat loads by blocking the passive cooler s view of the warm spacecraft. The technology significantly enhances the capabilities of instruments requiring either active or passive cooling of optical detectors. This can be particularly important for instruments where performance is limited by the available radiator area. Examples would be IR optical instruments on CubeSATs or those launched as hosted payloads because radiator area is limited and views are often undesirable. As a deployable radiator, the panels making up the FETS are linked thermally by thermal straps and heat pipes; the structural support and deployment energy is provided using tape-spring hinges. The FETS is a novel combination of existing technologies. Prior art for deployable heat shields uses rotating hinges that typically must be lubricated to avoid cold welding or static friction. By using tape-spring hinges, the FETS avoids the need for lubricants by avoiding friction altogether. This also eliminates the potential for contamination of nearby cooled optics by outgassing lubricants. Furthermore, the tape-spring design of the FETS is also self-locking so the panels stay in a rigid and extended configuration after deployment. This unexpected benefit makes the tape-spring hinge design of the FETS a light, simple, reliable, compact, non-outgassing hinge, spring, and latch. While tape-spring hinges are not novel, they have never been used to deploy passive unfolding thermal surfaces (radiator panels, covers, sun shades, or IR thermal shields). Furthermore, because this technology is compact, it has minimal impact on the launch envelope and mass specifications. FETS enhances the performance of hosted payload instruments where the science data is limited by dark noise. Incorporating FETS into a thermal control system increases radiator area, which lowers the optical detector temperature. This results in higher SNR (signal-to-noise ratio) and improved science data.
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X-ray structures of LeuT in substrate-free outward-open and apo inward-open states
DOE Office of Scientific and Technical Information (OSTI.GOV)
Krishnamurthy, Harini; Gouaux, Eric
2012-08-09
Neurotransmitter sodium symporters are integral membrane proteins that remove chemical transmitters from the synapse and terminate neurotransmission mediated by serotonin, dopamine, noradrenaline, glycine and GABA ({gamma}-aminobutyric acid). Crystal structures of the bacterial homologue, LeuT, in substrate-bound outward-occluded and competitive inhibitor-bound outward-facing states have advanced our mechanistic understanding of neurotransmitter sodium symporters but have left fundamental questions unanswered. Here we report crystal structures of LeuT mutants in complexes with conformation-specific antibody fragments in the outward-open and inward-open states. In the absence of substrate but in the presence of sodium the transporter is outward-open, illustrating how the binding of substrate closes themore » extracellular gate through local conformational changes: hinge-bending movements of the extracellular halves of transmembrane domains 1, 2 and 6, together with translation of extracellular loop 4. The inward-open conformation, by contrast, involves large-scale conformational changes, including a reorientation of transmembrane domains 1, 2, 5, 6 and 7, a marked hinge bending of transmembrane domain 1a and occlusion of the extracellular vestibule by extracellular loop 4. These changes close the extracellular gate, open an intracellular vestibule, and largely disrupt the two sodium sites, thus providing a mechanism by which ions and substrate are released to the cytoplasm. The new structures establish a structural framework for the mechanism of neurotransmitter sodium symporters and their modulation by therapeutic and illicit substances.« less
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Rázga, Filip; Koča, Jaroslav; Šponer, Jiří; Leontis, Neocles B.
2005-01-01
Kink-turn (K-turn) motifs are asymmetric internal loops found at conserved positions in diverse RNAs, with sharp bends in phosphodiester backbones producing V-shaped structures. Explicit-solvent molecular dynamics simulations were carried out for three K-turns from 23S rRNA, i.e., Kt-38 located at the base of the A-site finger, Kt-42 located at the base of the L7/L12 stalk, and Kt-58 located in domain III, and for the K-turn of human U4 snRNA. The simulations reveal hinge-like K-turn motions on the nanosecond timescale. The first conserved A-minor interaction between the K-turn stems is entirely stable in all simulations. The angle between the helical arms of Kt-38 and Kt-42 is regulated by local variations of the second A-minor (type I) interaction between the stems. Its variability ranges from closed geometries to open ones stabilized by insertion of long-residency waters between adenine and cytosine. The simulated A-minor geometries fully agree with x-ray data. Kt-58 and Kt-U4 exhibit similar elbow-like motions caused by conformational change of the adenosine from the nominally unpaired region. Despite the observed substantial dynamics of K-turns, key tertiary interactions are stable and no sign of unfolding is seen. We suggest that some K-turns are flexible elements mediating large-scale ribosomal motions during the protein synthesis cycle. PMID:15722438
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Yamasaki, Kazuo; Daiho, Takashi; Danko, Stefania; Suzuki, Hiroshi
2013-01-01
Sarcoplasmic reticulum Ca2+-ATPase couples the motions and rearrangements of three cytoplasmic domains (A, P, and N) with Ca2+ transport. We explored the role of electrostatic force in the domain dynamics in a rate-limiting phosphoenzyme (EP) transition by a systematic approach combining electrostatic screening with salts, computer analysis of electric fields in crystal structures, and mutations. Low KCl concentration activated and increasing salt above 0.1 m inhibited the EP transition. A plot of the logarithm of the transition rate versus the square of the mean activity coefficient of the protein gave a linear relationship allowing division of the activation energy into an electrostatic component and a non-electrostatic component in which the screenable electrostatic forces are shielded by salt. Results show that the structural change in the transition is sterically restricted, but that strong electrostatic forces, when K+ is specifically bound at the P domain, come into play to accelerate the reaction. Electric field analysis revealed long-range electrostatic interactions between the N and P domains around their hinge. Mutations of the residues directly involved and other charged residues at the hinge disrupted in parallel the electric field and the structural transition. Favorable electrostatics evidently provides a low energy path for the critical N domain motion toward the P domain, overcoming steric restriction. The systematic approach employed here is, in general, a powerful tool for understanding the structural mechanisms of enzymes. PMID:23737524
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T-Craft Seabase Ramp Loads Model Test Data Report
2010-12-01
INTRODUCTION 1 TEST CONDITION MATRIX 2 MODEL DESCRIPTIONS 9 LMSR Model 15 Ramp Models 17 MODEL TEST SETUP 18 Side-by-Side Hull Configuration 19... INTRODUCTION The Office of Naval Research (ONR) sponsored a multiple bodied seakeeping model test designed to investigate vessel motions and loads on the hinge...C. 3. Side-by-Side configuration 137 Ramp Load cell 1.88 27.49 -CG ft I ^ -Hinged Connection 3.00 from CL to jauge • oad ce LMSR
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Engineering design, stress and thermal analysis, and documentation for SATS program
NASA Technical Reports Server (NTRS)
1973-01-01
An in-depth analysis and mechanical design of the solar array stowage and deployment arrangements for use in Small Applications Technology Satellite spacecraft is presented. Alternate approaches for the major elements of work are developed and evaluated. Elements include array stowage and deployment arrangements, the spacecraft and array behavior in the spacecraft despin mode, and the design of the main hinge and segment hinge assemblies. Feasibility calculations are performed and the preferred approach is identified.
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Fiber Grating Moisture And Chemical Sensing System
Schipani, Claudia; Spano, Ennio; Dalle Crode, Domenico
2004-01-27
A vane for a stator of a variable-geometry turbine, in particular for aeronautical engines, has an airfoil profile and a pair of hinge portions, which are carried by the airfoil profile and enable the airfoil profile to be coupled to a support structure of the stator so as to be rotatable about an axis of adjustment; the vane also has internal channels that allow a flow of air to pass through in order to cool the hinge portions.
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NASA Technical Reports Server (NTRS)
Baucom, R. M. (Inventor)
1983-01-01
An X-ray transparent and biological inert medical clip for treating aneurisms and the like is described. A graphite reinforced composite film is molded into a unitary structure having a pair of hourglass-like cavities hinged together with a pair of jaws for grasping the aneurism extending from the wall of one cavity. A silicone rubber pellet is disposed in the other cavity to exert a spring force through the hinge area to normally bias the jaws into contact with each other.
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A Flight-Dynamic Helicopter Mathematical Model with a Single Flap-Lag- Torsion Main Rotor
1990-02-01
allows several hinge sequences and two offsets in the hinges. Quasi-steady Greenberg theory is used to calculate the blade-section aerodynamic forces...steady Greenberg model is used (ref. 3), Unsteady inflow effects are included using the three-state nonlinear Pitt/Peters dynamic inflow model (ref. 4...sectional aerodynamic model is based on quasi-steady Greenberg theory, which is a Theodorsen theory modified to account for lead-lag motions (refs. 3,14). The
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Localised JAK/STAT Pathway Activation Is Required for Drosophila Wing Hinge Development
Johnstone, Kirsty; Wells, Richard E.; Strutt, David; Zeidler, Martin P.
2013-01-01
Extensive morphogenetic remodelling takes place during metamorphosis from a larval to an adult insect body plan. These changes are particularly intricate in the generation of the dipteran wing hinge, a complex structure that is derived from an apparently simple region of the wing imaginal disc. Using the characterisation of original outstretched alleles of the unpaired locus as a starting point, we demonstrate the role of JAK/STAT pathway signalling in the process of wing hinge development. We show that differences in JAK/STAT signalling within the proximal most of three lateral folds present in the wing imaginal disc is required for fold morphology and the subsequent differentiation of the first and second auxiliary sclerites as well as the posterior notal wing process. Changes in these domains are consistent with the established fate map of the wing disc. We show that outstretched wing posture phenotypes arise from the loss of a region of Unpaired expression in the proximal wing fold and demonstrate that this results in a decrease in JAK/STAT pathway activity. Finally we show that reduction of JAK/STAT pathway activity within the proximal wing fold is sufficient to phenocopy the outstretched phenotype. Taken together, we suggest that localised Unpaired expression and hence JAK/STAT pathway activity, is required for the morphogenesis of the adult wing hinge, providing new insights into the link between signal transduction pathways, patterning and development. PMID:23741461
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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.
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Loads Model Development and Analysis for the F/A-18 Active Aeroelastic Wing Airplane
NASA Technical Reports Server (NTRS)
Allen, Michael J.; Lizotte, Andrew M.; Dibley, Ryan P.; Clarke, Robert
2005-01-01
The Active Aeroelastic Wing airplane was successfully flight-tested in March 2005. During phase 1 of the two-phase program, an onboard excitation system provided independent control surface movements that were used to develop a loads model for the wing structure and wing control surfaces. The resulting loads model, which was used to develop the control laws for phase 2, is described. The loads model was developed from flight data through the use of a multiple linear regression technique. The loads model input consisted of aircraft states and control surface positions, in addition to nonlinear inputs that were calculated from flight-measured parameters. The loads model output for each wing consisted of wing-root bending moment and torque, wing-fold bending moment and torque, inboard and outboard leading-edge flap hinge moment, trailing-edge flap hinge moment, and aileron hinge moment. The development of the Active Aeroelastic Wing loads model is described, and the ability of the model to predict loads during phase 2 research maneuvers is demonstrated. Results show a good match to phase 2 flight data for all loads except inboard and outboard leading-edge flap hinge moments at certain flight conditions. The average load prediction errors for all loads at all flight conditions are 9.1 percent for maximum stick-deflection rolls, 4.4 percent for 5-g windup turns, and 7.7 percent for 4-g rolling pullouts.
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Antibody proteolysis: a common picture emerging from plants
Donini, Marcello; Lombardi, Raffaele; Lonoce, Chiara; Di Carli, Mariasole; Marusic, Carla; Morea, Veronica; Di Micco, Patrizio
2015-01-01
We have recently characterized the degradation profiles of 2 human IgG1 monoclonal antibodies, the tumor-targeting mAb H10 and the anti-HIV mAb 2G12. Both mAbs were produced in plants either as stable transgenics or using a transient expression system based on leaf agroinfiltration. The purified antibodies were separated by 1DE and protein bands were characterized by N-terminal sequencing. The proteolytic cleavage sites identified in the heavy chain (HC) of both antibodies were localized in 3 inter-domain regions, suggesting that the number of proteolytic cleavage events taking place in plants is limited. One of the cleavage sites, close to the hinge region, was common to both antibodies. PMID:26186119
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From the Cover: Visualization of maltose uptake in living yeast cells by fluorescent nanosensors
NASA Astrophysics Data System (ADS)
Fehr, Marcus; Frommer, Wolf B.; Lalonde, Sylvie
2002-07-01
Compartmentation of metabolic reactions and thus transport within and between cells can be understood only if we know subcellular distribution based on nondestructive dynamic monitoring. Currently, methods are not available for in vivo metabolite imaging at cellular or subcellular levels. Limited information derives from methods requiring fixation or fractionation of tissue (1, 2). We thus developed a flexible strategy for designing protein-based nanosensors for a wide spectrum of solutes, allowing analysis of changes in solute concentration in living cells. We made use of bacterial periplasmic binding proteins (PBPs), where we show that, on binding of the substrate, PBPs transform their hinge-bend movement into increased fluorescence resonance energy transfer (FRET) between two coupled green fluorescent proteins. By using the maltose-binding protein as a prototype, nanosensors were constructed allowing in vitro determination of FRET changes in a concentration-dependent fashion. For physiological applications, mutants with different binding affinities were generated, allowing dynamic in vivo imaging of the increase in cytosolic maltose concentration in single yeast cells. Control sensors allow the exclusion of the effect from other cellular or environmental parameters on ratio imaging. Thus the myriad of PBPs recognizing a wide spectrum of different substrates is suitable for FRET-based in vivo detection, providing numerous scientific, medical, and environmental applications.
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Wang, Hsin-Wei; Hsu, Yen-Chu; Hwang, Jenn-Kang; Lyu, Ping-Chiang; Pai, Tun-Wen; Tang, Chuan Yi
2010-01-01
This work presents a novel detection method for three-dimensional domain swapping (DS), a mechanism for forming protein quaternary structures that can be visualized as if monomers had “opened” their “closed” structures and exchanged the opened portion to form intertwined oligomers. Since the first report of DS in the mid 1990s, an increasing number of identified cases has led to the postulation that DS might occur in a protein with an unconstrained terminus under appropriate conditions. DS may play important roles in the molecular evolution and functional regulation of proteins and the formation of depositions in Alzheimer's and prion diseases. Moreover, it is promising for designing auto-assembling biomaterials. Despite the increasing interest in DS, related bioinformatics methods are rarely available. Owing to a dramatic conformational difference between the monomeric/closed and oligomeric/open forms, conventional structural comparison methods are inadequate for detecting DS. Hence, there is also a lack of comprehensive datasets for studying DS. Based on angle-distance (A-D) image transformations of secondary structural elements (SSEs), specific patterns within A-D images can be recognized and classified for structural similarities. In this work, a matching algorithm to extract corresponding SSE pairs from A-D images and a novel DS score have been designed and demonstrated to be applicable to the detection of DS relationships. The Matthews correlation coefficient (MCC) and sensitivity of the proposed DS-detecting method were higher than 0.81 even when the sequence identities of the proteins examined were lower than 10%. On average, the alignment percentage and root-mean-square distance (RMSD) computed by the proposed method were 90% and 1.8Å for a set of 1,211 DS-related pairs of proteins. The performances of structural alignments remain high and stable for DS-related homologs with less than 10% sequence identities. In addition, the quality of its hinge loop determination is comparable to that of manual inspection. This method has been implemented as a web-based tool, which requires two protein structures as the input and then the type and/or existence of DS relationships between the input structures are determined according to the A-D image-based structural alignments and the DS score. The proposed method is expected to trigger large-scale studies of this interesting structural phenomenon and facilitate related applications. PMID:20976204
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Improved design of support for large aperture space lightweight mirror
NASA Astrophysics Data System (ADS)
Wang, Chao; Ruan, Ping; Liu, Qimin
2013-08-01
In order to design a kind of rational large aperture space mirror which can adapt to the space gravity and thermal environment, by taking the choice of material, the lightweight of the mirror and the design of support into account in detail, a double-deck structure with traditional flexible hinge was designed, then the analytical mathematical model of the mirror system was established. The design adopts six supports on back. in order to avoid the constraints, mirror is connected to three middle transition pieces through six flexible hinges, and then the three transition pieces are connected to support plate through another three flexible hinges. However, the initial structure is unable to reach the expected design target and needs to be made further adjustments. By improving and optimizing the original structure, a new type of flexible hinge in the shape of the letter A is designed finally. Compared with the traditional flexible hinge structure, the new structure is simpler and has less influence on the surface figure accuracy of mirror. By using the finite element analysis method, the static and dynamic characteristics as well as the thermal characteristics of the mirror system are analyzed. Analysis results show that the maximum PV value is 37 nm and the maximum RMS value is 10.4 nm when gravity load is applied. Furthermore, the maximum PV value is 46 nm and the maximum RMS value is 10.5 nm under the load case of gravity coupled with 4℃ uniform temperature rise. The results satisfy the index of optical design. The first order natural frequency of the mirror component is 130 Hz according to the conclusion obtained by modal analytical solution, so the mirror structure has high enough fundamental frequency. And, the structural strength can meet the demand under the overload and the random vibration environment respectively. It indicates that the mirror component structure has enough dynamic, static stiffness and thermal stability, meeting the design requirements.
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Park, Jeung Kuk; Kim, Sunmin; Han, Yu Jin; Kim, Seong Hwan; Kang, Nam Sook; Lee, Hyuk; Park, SangYoun
2016-06-01
p21-Activated kinases (PAKs) which belong to the family of ste20 serine/threonine protein kinases regulate cytoskeletal reorganization, cell motility, cell proliferation, and oncogenic transformation which are all related to the cellular functions during cancer induction and metastasis. The fact that PAK mutations are detected in multiple tumor tissues makes PAKs a novel therapeutic drug target. In this study, an imidazo[4,5-b]pyridine-based PAK4 inhibitor, KY-04045 (6-Bromo-2-(3-isopropyl-1-methyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridine), was discovered using a virtual site-directed fragment-based drug design and was validated using an inhibition assay. Although PAK4 affinity to KY-04045 seems much weaker than that of the reported PAK4 inhibitors, the location of KY-04045 is clearly defined in the structure of PAK4 co-crystallized with KY-04045. The crystal structure illustrates that the pyrazole and imidazopyridine rings of KY-04045 are sufficient for mediating PAK4 hinge loop interaction. Hence, we believe that KY-04045 can be exploited as a basic building block in designing novel imidazo[4,5-b]pyridine-based PAK4 inhibitors. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Selvaraman, Nagamani; Selvam, Saravana Kumar; Muthusamy, Karthikeyan
2016-08-01
Non-secosteroidal ligands are well-known vitamin D receptor (VDR) agonists. In this study, we described a combined QM/MM to define the protein-ligand interaction energy a strong positive correlation in both QM-MM interaction energy and binding free energy against the biological activity. The molecular dynamics simulation study was performed, and specific interactions were extensively studied. The molecular docking results and surface analysis shed light on steric and electrostatic complementarities of these non-secosteroidal ligands to VDR. Finally, the drug likeness properties were also calculated and found within the acceptable range. The results show that bulky group substitutions in side chain decrease the VDR activity, whereas a small substitution increased it. Functional analyses of H393A and H301A mutations substantiate their roles in the VDR agonistic and antagonistic activities. Apart from the His393 and His301, two other amino acids in the hinge region viz. Ser233 and Arg270 acted as an electron donor/acceptor specific to the agonist in the distinct ligand potency. The results from this study disclose the binding mechanism of VDR agonists and structural modifications required to improve the selectivity. © 2016 John Wiley & Sons A/S.
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Structural Plasticity and Conformational Transitions of HIV Envelope Glycoprotein gp120
Korkut, Anil; Hendrickson, Wayne A.
2012-01-01
HIV envelope glycoproteins undergo large-scale conformational changes as they interact with cellular receptors to cause the fusion of viral and cellular membranes that permits viral entry to infect targeted cells. Conformational dynamics in HIV gp120 are also important in masking conserved receptor epitopes from being detected for effective neutralization by the human immune system. Crystal structures of HIV gp120 and its complexes with receptors and antibody fragments provide high-resolution pictures of selected conformational states accessible to gp120. Here we describe systematic computational analyses of HIV gp120 plasticity in such complexes with CD4 binding fragments, CD4 mimetic proteins, and various antibody fragments. We used three computational approaches: an isotropic elastic network analysis of conformational plasticity, a full atomic normal mode analysis, and simulation of conformational transitions with our coarse-grained virtual atom molecular mechanics (VAMM) potential function. We observe collective sub-domain motions about hinge points that coordinate those motions, correlated local fluctuations at the interfacial cavity formed when gp120 binds to CD4, and concerted changes in structural elements that form at the CD4 interface during large-scale conformational transitions to the CD4-bound state from the deformed states of gp120 in certain antibody complexes. PMID:23300605
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Hydrodynamics of metachronal paddling in crustaceans
NASA Astrophysics Data System (ADS)
Santhanakrishnan, A.; Lai, H. K.; Samaee, M.; Lewis, T. J.; Guy, R. D.
2016-02-01
Long-tailed crustaceans such as crayfish and krill swim by rhythmically paddling a set of four to five limbs (swimmerets) originating from their abdomen. Despite variations in limb size and stroke frequency, movements of ipsilateral limbs always maintain a tail-to-head metachronal rhythm with an approximate quarter-period inter-limb phase difference. Relatively few studies have examined the fluid dynamics of metachronal limb stroke for the range of Reynolds numbers at which crustaceans operate. The objective of this study is to investigate metachronal paddling as a function of Reynolds number (Re) for quantifying hydrodynamic scalability of this swimming mechanism, including the effect of hinges on paddles as seen in crustacean swimmerets. Our approach included experiments on a scaled physical model and computational fluid dynamics (CFD) simulations using the immersed boundary (IB) method. The scaled robotic model of metachronal paddling consisted of a rectangular aquarium tank fitted above with four stepper motors coupled to a four-bar linkage that actuated four acrylic paddles immersed in water-glycerin fluid medium. 2D particle image velocimetry (PIV) was used for quantitative flow visualization in the experiments. The swimmerets were modeled in CFD simulations as rigid 1D rods in a 2D fluid. The inter-limb phase difference was varied from 0% (synchronous paddling) through 50% across Re range of O(10-1000). Two types of experimental limb models were tested, including a simple flat plate and a `split-paddle' structure with two flat plates connected halfway with hinges. Our results show that the natural tail-to-head metachronal rhythm with an approximate quarter-period phase difference is the most effective and efficient rhythm across a wide range of Reynolds numbers. Limb models with hinges generated increased horizontal flow compared to the simple flat plate paddles, suggesting that asymmetry between power and return stroke is important to augment thrust.
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Costa, M G S; Silva, Y F; Batista, P R
2018-03-14
Microbial cellulosic degradation by cellulases has become a complementary approach for biofuel production. However, its efficiency is hindered by the recalcitrance of cellulose fibres. In this context, computational protein design methods may offer an efficient way to obtain variants with improved enzymatic activity. Cel9A-68 is a cellulase from Thermobifida fusca that is still active at high temperatures. In a previous work, we described a collective bending motion, which governs the overall cellulase dynamics. This movement promotes the approximation of its CBM and CD structural domains (that are connected by a flexible linker). We have identified two residues (G460 and P461) located at the linker that act as a hinge point. Herein, we applied a new level of protein design, focusing on the modulation of this collective motion to obtain cellulase variants with enhanced functional dynamics. We probed whether specific linker mutations would affect Cel9A-68 dynamics through computational simulations. We assumed that P461G and G460+ (with an extra glycine) constructs would present enhanced interdomain motions, while the G460P mutant would be rigid. From our results, the P461G mutation resulted in a broader exploration of the conformational space, as confirmed by clustering and free energy analyses. The WT enzyme was the most rigid system. However, G460P and P460+ explored distinct conformational states described by opposite directions of low-frequency normal modes; they sampled preferentially closed and open conformations, respectively. Overall, we highlight two significant findings: (i) all mutants explored larger conformational spaces than the WT; (ii) the selection of distinct conformational populations was intimately associated with the mutation considered. Thus, the engineering of Cel9A-68 motions through linker mutations may constitute an efficient way to improve cellulase activity, facilitating the disruption of cellulose fibres.
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Magnetic Actuation of Biological Systems
NASA Astrophysics Data System (ADS)
Lauback, Stephanie D.
Central to the advancement of many biomedical and nanotechnology capabilities is the capacity to precisely control the motion of micro and nanostructures. These applications range from single molecule experiments to cell isolation and separation, to drug delivery and nanomachine manipulation. This dissertation focuses on actuation of biological micro- and nano-entities through the use of weak external magnetic fields, superparamagnetic beads, and ferromagnetic thin films. The magnetic platform presents an excellent method for actuation of biological systems due to its ability to directly control the motion of an array of micro and nanostructures in real-time with calibrated picoNewton forces. The energy landscape of two ferromagnetic thin film patterns (disks and zigzag wires) is experimentally explored and compared to corresponding theoretical models to quantify the applied forces and trajectories of superparamagnetic beads due to the magnetic traps. A magnetic method to directly actuate DNA nanomachines in real-time with nanometer resolution and sub-second response times using micromagnetic control was implemented through the use of stiff DNA micro-levers which bridged the large length scale mismatch between the micro-actuator and the nanomachine. Compared to current alternative methods which are limited in the actuation speeds and the number of reconfiguration states of DNA constructs, this magnetic approach enables fast actuation (˜ milliseconds) and reconfigurable conformations achieved through a continuous range of finely tuned steps. The system was initially tested through actuation of the stiff arm tethered to the surface, and two prototype DNA nanomachines (rotor and hinge) were successfully actuated using the stiff mechanical lever. These results open new possibilities in the development of functional robotic systems at the molecular scale. In exploiting the use of DNA stiff levers, a new technique was also developed to investigate the emergence of the magnetization of individual superparamagnetic beads as a function of the applied field. Last, since proteins are frequently used for surface adhesion in assembling biomedical devices, preliminary tests were implemented to dynamically pattern proteins on a substrate using transformed E. coli that are magnetically labeled.
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Algorithms for the Reduction of Wind-Tunnel Data Derived from Strain Gauge Force Balances.
1984-05-01
summed. Where hinge moments are measured on a model, it is customary to express them by coefficients of the form C11 h (4.23) q Si dH where hi is the...measured hinge moment and Sit and dH are a characteristic area and length associated with the control surface. 4.6 Transformation to Body Axes...Pty. Ltd. Mr D. Pilkington Mr R. D. Bullen Commonwealth Aircraft Corporation, Libra Hawker de Havilland Aust. Pty. Ltd., Bankstown. L.ibrar
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NASA Technical Reports Server (NTRS)
Goin, Kennith L
1951-01-01
Existing conical-flow solutions have been used to calculate the hinge-moments and effectiveness parameters of trailing-edge controls having leading and trailing edges swept ahead of the Mach lines and having streamwise root and tip chords. Equations and detailed charts are presented for the rapid estimation of these parameters. Also included is an approximate method by which these parameters may be corrected for airfoil-section thickness.
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Structural Analysis of a Magnetically Actuated Silicon Nitride Micro-Shutter for Space Applications
NASA Technical Reports Server (NTRS)
Loughlin, James P.; Fettig, Rainer K.; Moseley, S. Harvey; Kutyrev, Alexander S.; Mott, D. Brent; Obenschain, Arthur F. (Technical Monitor)
2002-01-01
Finite element models have been created to simulate the electrostatic and electromagnetic actuation of a 0.5 micrometers silicon nitride micro-shutter for use in a spacebased Multi-object Spectrometer (MOS). The microshutter uses a torsion hinge to go from the closed, 0 degree, position, to the open, 90 degree position. Stresses in the torsion hinge are determined with a large deformation nonlinear finite element model. The simulation results are compared to experimental measurements of fabricated micro-shutter devices.
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NASA Technical Reports Server (NTRS)
Likins, P. W.
1974-01-01
Equations of motion are derived for use in simulating a spacecraft or other complex electromechanical system amenable to idealization as a set of hinge-connected rigid bodies of tree topology, with rigid axisymmetric rotors and nonrigid appendages attached to each rigid body in the set. In conjunction with a previously published report on finite-element appendage vibration equations, this report provides a complete minimum-dimension formulation suitable for generic programming for digital computer numerical integration.
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[Mid-term effectiveness of rotating hinge knee prosthesis for severe knee deformity].
Zeng, Min; Hu, Yihe; Xie, Jie; Li, Mingqing; Lin, Shaoru
2014-01-01
To evaluate the mid-term effectiveness of rotating hinge knee prosthesis for severe knee deformity. A retrospective analysis was made on the clinical data of 24 patients (24 knees) who received rotating hinge knee prosthesis for total knee arthroplasty between January 2003 and June 2011. There were 14 males and 10 females, aged from 60 to 81 years (mean, 70 years). The disease causes included osteoarthritis in 5 cases, rheumatoid arthritis in 7 cases, traumatic arthritis in 9 cases, and Charcot's arthropathy in 3 cases. The disease duration ranged from 5 to 25 years (mean, 14.5 years). Of them, 13 cases had flexion deformity, 7 cases had valgus deformity, and 16 cases had varus deformity. The operation time, the amount of bleeding between operation and drainage-tubes removal, hospitalization time, incision healing, and complications were recorded. The results were evaluated according to Knee Society Score (KSS), visual analogue scale (VAS), and the range of motion (ROM) of knee. Short-form 36 health survey scale (SF-36) was used to evaluate the life quality of patients. The position of prosthesis was observed through X-ray examination. The operation time ranged from 70 to 90 minutes (mean, 78 minutes). The amount of bleeding between operation and drainage-tubes removal ranged from 400 to 1 000 mL (mean, 650 mL). The hospitalization time ranged from 14 to 18 days (mean, 15.2 days). Patellar fracture occurred in 1 case (4.17%) during operation, swelling and effusion of incision in 1 case (4.17%), and periprosthetic infections in 2 cases (8.33%) after operation. All patients were followed up 2-10 years (mean, 5.5 years). The X-ray films showed no evidence of obvious radiolucent line, osteolysis, prosthesis subsidence, and limb alignment change. The results of KSS, VAS socres, and ROM of knee at 1 year postoperatively and last follow-up were significantly better than preoperative ones (P < 0.05), but no significant difference was found between at 1 year postoperatively and last follow-up (P > 0.05). The physiological function and body pain scores were significantly lower than the reference value of urban men over 60 years old from Sichuan province (t = 2.42, P = 0.02; t = 5.26, P = 0.00), but no significant difference was found in the other scores of the SF-36 when compared with the reference value (P > 0.05). The mid-term effectiveness of total knee arthroplasty using rotating hinge knee for severe knee prosthesis deformity is satisfactory. But complications of postoperative infection should be emphasized.
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Crystal Structure of the Japanese Encephalitis Virus Envelope Protein
DOE Office of Scientific and Technical Information (OSTI.GOV)
Luca, Vincent C.; AbiMansour, Jad; Nelson, Christopher A.
2012-03-13
Japanese encephalitis virus (JEV) is the leading global cause of viral encephalitis. The JEV envelope protein (E) facilitates cellular attachment and membrane fusion and is the primary target of neutralizing antibodies. We have determined the 2.1-{angstrom} resolution crystal structure of the JEV E ectodomain refolded from bacterial inclusion bodies. The E protein possesses the three domains characteristic of flavivirus envelopes and epitope mapping of neutralizing antibodies onto the structure reveals determinants that correspond to the domain I lateral ridge, fusion loop, domain III lateral ridge, and domain I-II hinge. While monomeric in solution, JEV E assembles as an antiparallel dimermore » in the crystal lattice organized in a highly similar fashion as seen in cryo-electron microscopy models of mature flavivirus virions. The dimer interface, however, is remarkably small and lacks many of the domain II contacts observed in other flavivirus E homodimers. In addition, uniquely conserved histidines within the JEV serocomplex suggest that pH-mediated structural transitions may be aided by lateral interactions outside the dimer interface in the icosahedral virion. Our results suggest that variation in dimer structure and stability may significantly influence the assembly, receptor interaction, and uncoating of virions.« less
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Crystal structure of the Japanese encephalitis virus envelope protein.
Luca, Vincent C; AbiMansour, Jad; Nelson, Christopher A; Fremont, Daved H
2012-02-01
Japanese encephalitis virus (JEV) is the leading global cause of viral encephalitis. The JEV envelope protein (E) facilitates cellular attachment and membrane fusion and is the primary target of neutralizing antibodies. We have determined the 2.1-Å resolution crystal structure of the JEV E ectodomain refolded from bacterial inclusion bodies. The E protein possesses the three domains characteristic of flavivirus envelopes and epitope mapping of neutralizing antibodies onto the structure reveals determinants that correspond to the domain I lateral ridge, fusion loop, domain III lateral ridge, and domain I-II hinge. While monomeric in solution, JEV E assembles as an antiparallel dimer in the crystal lattice organized in a highly similar fashion as seen in cryo-electron microscopy models of mature flavivirus virions. The dimer interface, however, is remarkably small and lacks many of the domain II contacts observed in other flavivirus E homodimers. In addition, uniquely conserved histidines within the JEV serocomplex suggest that pH-mediated structural transitions may be aided by lateral interactions outside the dimer interface in the icosahedral virion. Our results suggest that variation in dimer structure and stability may significantly influence the assembly, receptor interaction, and uncoating of virions.
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NASA Astrophysics Data System (ADS)
Neumann, Lars; Ritscher, Allegra; Müller, Gerhard; Hafenbradl, Doris
2009-08-01
For the detection of the precise and unambiguous binding of fragments to a specific binding site on the target protein, we have developed a novel reporter displacement binding assay technology. The application of this technology for the fragment screening as well as the fragment evolution process with a specific modelling based design strategy is demonstrated for inhibitors of the protein kinase p38alpha. In a fragment screening approach seed fragments were identified which were then used to build compounds from the deep-pocket towards the hinge binding area of the protein kinase p38alpha based on a modelling approach. BIRB796 was used as a blueprint for the alignment of the fragments. The fragment evolution of these deep-pocket binding fragments towards the fully optimized inhibitor BIRB796 included the modulation of the residence time as well as the affinity. The goal of our study was to evaluate the robustness and efficiency of our novel fragment screening technology at high fragment concentrations, compare the screening data with biochemical activity data and to demonstrate the evolution of the hit fragments with fast kinetics, into slow kinetic inhibitors in an in silico approach.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Mueser, Timothy C., E-mail: timothy.mueser@utoledo.edu; Griffith, Wendell P.; Kovalevsky, Andrey Y.
2010-11-01
X-ray and neutron diffraction studies of cyanomethemoglobin are being used to evaluate the structural waters within the dimer–dimer interface involved in quaternary-state transitions. Improvements in neutron diffraction instrumentation are affording the opportunity to re-examine the structures of vertebrate hemoglobins and to interrogate proton and solvent position changes between the different quaternary states of the protein. For hemoglobins of unknown primary sequence, structural studies of cyanomethemoglobin (CNmetHb) are being used to help to resolve sequence ambiguity in the mass spectra. These studies have also provided additional structural evidence for the involvement of oxidized hemoglobin in the process of erythrocyte senescence. X-raymore » crystal studies of Tibetan snow leopard CNmetHb have shown that this protein crystallizes in the B state, a structure with a more open dyad, which possibly has relevance to RBC band 3 protein binding and erythrocyte senescence. R-state equine CNmetHb crystal studies elaborate the solvent differences in the switch and hinge region compared with a human deoxyhemoglobin T-state neutron structure. Lastly, comparison of histidine protonation between the T and R state should enumerate the Bohr-effect protons.« less
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NMR investigations of molecular dynamics
NASA Astrophysics Data System (ADS)
Palmer, Arthur
2011-03-01
NMR spectroscopy is a powerful experimental approach for characterizing protein conformational dynamics on multiple time scales. The insights obtained from NMR studies are complemented and by molecular dynamics (MD) simulations, which provide full atomistic details of protein dynamics. Homologous mesophilic (E. coli) and thermophilic (T. thermophilus) ribonuclease H (RNase H) enzymes serve to illustrate how changes in protein sequence and structure that affect conformational dynamic processes can be monitored and characterized by joint analysis of NMR spectroscopy and MD simulations. A Gly residue inserted within a putative hinge between helices B and C is conserved among thermophilic RNases H, but absent in mesophilic RNases H. Experimental spin relaxation measurements show that the dynamic properties of T. thermophilus RNase H are recapitulated in E. coli RNase H by insertion of a Gly residue between helices B and C. Additional specific intramolecular interactions that modulate backbone and sidechain dynamical properties of the Gly-rich loop and of the conserved Trp residue flanking the Gly insertion site have been identified using MD simulations and subsequently confirmed by NMR spin relaxation measurements. These results emphasize the importance of hydrogen bonds and local steric interactions in restricting conformational fluctuations, and the absence of such interactions in allowing conformational adaptation to substrate binding.
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Pivotal role of extended linker 2 in the activation of Gα by G protein-coupled receptor.
Huang, Jianyun; Sun, Yutong; Zhang, J Jillian; Huang, Xin-Yun
2015-01-02
G protein-coupled receptors (GPCRs) relay extracellular signals mainly to heterotrimeric G-proteins (Gαβγ) and they are the most successful drug targets. The mechanisms of G-protein activation by GPCRs are not well understood. Previous studies have revealed a signal relay route from a GPCR via the C-terminal α5-helix of Gα to the guanine nucleotide-binding pocket. Recent structural and biophysical studies uncover a role for the opening or rotating of the α-helical domain of Gα during the activation of Gα by a GPCR. Here we show that β-adrenergic receptors activate eight Gαs mutant proteins (from a screen of 66 Gαs mutants) that are unable to bind Gβγ subunits in cells. Five of these eight mutants are in the αF/Linker 2/β2 hinge region (extended Linker 2) that connects the Ras-like GTPase domain and the α-helical domain of Gαs. This extended Linker 2 is the target site of a natural product inhibitor of Gq. Our data show that the extended Linker 2 is critical for Gα activation by GPCRs. We propose that a GPCR via its intracellular loop 2 directly interacts with the β2/β3 loop of Gα to communicate to Linker 2, resulting in the opening and closing of the α-helical domain and the release of GDP during G-protein activation. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.
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Modeling and design of a two-axis elliptical notch flexure hinge
NASA Astrophysics Data System (ADS)
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.
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Determination of Elevator and Rudder Hinge Forces on the Learjet Model 55 Aircraft
NASA Technical Reports Server (NTRS)
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.
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NASA Astrophysics Data System (ADS)
McMahon, Paul; Jung, Hans-Juergen; Edwards, Jeff
2013-09-01
The Swarm programme consists of 3 magnetically clean satellites flying in close formation designed to measure the Earth's magnetic field using 2 Magnetometers mounted on a 4.3m long deployable boom.Deployment is initiated by releasing 3 HDRMs, once released the boom oscillates back and forth on a pair of pivots, similar to a restaurant kitchen door hinge, for around 120 seconds before coming to rest on 3 kinematic mounts which are used to provide an accurate reference location in the deployed position. Motion of the boom is damped through a combination of friction, spring hysteresis and flexing of the 120+ cables crossing the hinge. Considerable development work and accurate numerical modelling of the hinge motion was required to predict performance across a wide temperature range and ensure that during the 1st overshoot the boom did not damage itself, the harness or the spacecraft.Due to the magnetic cleanliness requirements of the spacecraft no magnetic materials could be used in the design of the hardware.
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Bioengineered nisin derivatives with enhanced activity in complex matrices
Rouse, Susan; Field, Des; Daly, Karen M.; O'Connor, Paula M.; Cotter, Paul D.; Hill, Colin; Ross, R. Paul
2012-01-01
Summary Nisin A is the best known and most extensively characterized lantibiotic. As it is ribosomally synthesized, bioengineering‐based strategies can be used to generate variants. We have previously demonstrated that bioengineering of the hinge region of nisin A can result in the generation of variants with enhanced anti‐microbial activity against Gram‐positive pathogens. Here we created a larger bank of hinge variant producers and screened for producers that exhibit enhanced bioactivity as assessed by agar‐based assays against a selection of target strains. Further analysis of 12 ‘lead’ variants reveals that in many cases enhanced bioactivity is not attributable to enhanced specific activity but is instead as a consequence of an enhanced ability to diffuse through complex polymers. In the case of two variants, which contain the residues SVA and NAK, respectively, within the hinge region, we demonstrate that this enhanced trait enables the peptides to dramatically outperform nisin A with respect to controlling Listeria monocytogenes in commercially produced chocolate milk that contains carrageenan as a stabilizer. PMID:22260415
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NASA Astrophysics Data System (ADS)
Tapken, Daniel; Steffensen, Thomas Bielefeldt; Leth, Rasmus; Kristensen, Lise Baadsgaard; Gerbola, Alexander; Gajhede, Michael; Jørgensen, Flemming Steen; Olsen, Lars; Kastrup, Jette Sandholm
2017-04-01
Ionotropic glutamate receptors (iGluRs) are responsible for most of the fast excitatory communication between neurons in our brain. The GluD2 receptor is a puzzling member of the iGluR family: It is involved in synaptic plasticity, plays a role in human diseases, e.g. ataxia, binds glycine and D-serine with low affinity, yet no ligand has been discovered so far that can activate its ion channel. In this study, we show that the hinge region connecting the two subdomains of the GluD2 ligand-binding domain is responsible for the low affinity of D-serine, by analysing GluD2 mutants with electrophysiology, isothermal titration calorimetry and molecular dynamics calculations. The hinge region is highly variable among iGluRs and fine-tunes gating activity, suggesting that in GluD2 this region has evolved to only respond to micromolar concentrations of D-serine.
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Role for the MED21-MED7 Hinge in Assembly of the Mediator-RNA Polymerase II Holoenzyme.
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; Conaway, Joan W
2016-12-23
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. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
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Geothermal energy prospectivity of the Torrens Hinge Zone: evidence from new heat flow data
NASA Astrophysics Data System (ADS)
Matthews, Chris
2009-09-01
The Torrens Hinge Zone is a long but narrow (up to 40km wide) geological transition zone between the relatively stable Eastern Gawler Craton `Olympic Domain' to the west, and the sedimentary basin known as the Adelaide Geosyncline to the east. The author hypothesised from first principles that the Torrens Hinge Zone should be prospective for high geothermal gradients due to the likely presence of high heat flow and insulating cover rocks. A method to test this hypothesis was devised, which involved the determination of surface heat flow on a pattern grid using purpose-drilled wells, precision temperature logging and detailed thermal conductivity measurements. The results of this structured test have validated the hypothesis, with heat flow values over 90mW/m2 recorded in five of six wells drilled. With several kilometres thickness of moderate conductivity sediments overlying the crystalline basement in this region, predicted temperature at 5000m ranges between 200 and 300°C.
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Tapken, Daniel; Steffensen, Thomas Bielefeldt; Leth, Rasmus; Kristensen, Lise Baadsgaard; Gerbola, Alexander; Gajhede, Michael; Jørgensen, Flemming Steen; Olsen, Lars; Kastrup, Jette Sandholm
2017-04-07
Ionotropic glutamate receptors (iGluRs) are responsible for most of the fast excitatory communication between neurons in our brain. The GluD2 receptor is a puzzling member of the iGluR family: It is involved in synaptic plasticity, plays a role in human diseases, e.g. ataxia, binds glycine and D-serine with low affinity, yet no ligand has been discovered so far that can activate its ion channel. In this study, we show that the hinge region connecting the two subdomains of the GluD2 ligand-binding domain is responsible for the low affinity of D-serine, by analysing GluD2 mutants with electrophysiology, isothermal titration calorimetry and molecular dynamics calculations. The hinge region is highly variable among iGluRs and fine-tunes gating activity, suggesting that in GluD2 this region has evolved to only respond to micromolar concentrations of D-serine.
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Tapken, Daniel; Steffensen, Thomas Bielefeldt; Leth, Rasmus; Kristensen, Lise Baadsgaard; Gerbola, Alexander; Gajhede, Michael; Jørgensen, Flemming Steen; Olsen, Lars; Kastrup, Jette Sandholm
2017-01-01
Ionotropic glutamate receptors (iGluRs) are responsible for most of the fast excitatory communication between neurons in our brain. The GluD2 receptor is a puzzling member of the iGluR family: It is involved in synaptic plasticity, plays a role in human diseases, e.g. ataxia, binds glycine and D-serine with low affinity, yet no ligand has been discovered so far that can activate its ion channel. In this study, we show that the hinge region connecting the two subdomains of the GluD2 ligand-binding domain is responsible for the low affinity of D-serine, by analysing GluD2 mutants with electrophysiology, isothermal titration calorimetry and molecular dynamics calculations. The hinge region is highly variable among iGluRs and fine-tunes gating activity, suggesting that in GluD2 this region has evolved to only respond to micromolar concentrations of D-serine. PMID:28387240
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A flight-dynamic helicopter mathematical model with a single flap-lag-torsion main rotor
NASA Technical Reports Server (NTRS)
Takahashi, Marc D.
1990-01-01
A mathematical model of a helicopter system with a single main rotor that includes rigid, hinge-restrained rotor blades with flap, lag, and torsion degrees of freedom is described. The model allows several hinge sequences and two offsets in the hinges. Quasi-steady Greenberg theory is used to calculate the blade-section aerodynamic forces, and inflow effects are accounted for by using three-state nonlinear dynamic inflow model. The motion of the rigid fuselage is defined by six degrees of freedom, and an optional rotor rpm degree of freedom is available. Empennage surfaces and the tail rotor are modeled, and the effect of main-rotor downwash on these elements is included. Model trim linearization, and time-integration operations are described and can be applied to a subset of the model in the rotating or nonrotating coordinate frame. A preliminary validation of the model is made by comparing its results with those of other analytical and experimental studies. This publication presents the results of research compiled in November 1989.
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NASA Technical Reports Server (NTRS)
Taylor, John G.
1990-01-01
An investigation was conducted in the Static Test Facility of the NASA Langley 16-Foot Transonic Tunnel to determine the internal performance of two-dimensional convergent-divergent nozzles designed to have simultaneous pitch and yaw thrust vectoring capability. This concept utilized divergent flap rotation of thrust vectoring in the pitch plane and deflection of flat yaw flaps hinged at the end of the sidewalls for yaw thrust vectoring. The hinge location of the yaw flaps was varied at four positions from the nozzle exit plane to the throat plane. The yaw flaps were designed to contain the flow laterally independent of power setting. In order to eliminate any physical interference between the yaw flap deflected into the exhaust stream and the divergent flaps, the downstream corners of both upper and lower divergent flaps were cut off to allow for up to 30 deg of yaw flap deflection. The impact of varying the nozzle pitch vector angle, throat area, yaw flap hinge location, yaw flap length, and yaw flap deflection angle on nozzle internal performance characteristics, was studied. High-pressure air was used to simulate jet exhaust at nozzle pressure ratios up to 7.0. Static results indicate that configurations with the yaw flap hinge located upstream of the exit plane provide relatively high levels of thrust vectoring efficiency without causing large losses in resultant thrust ratio. Therefore, these configurations represent a viable concept for providing simultaneous pitch and yaw thrust vectoring.
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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.
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Shape Memory Alloy-Based Soft Gripper with Variable Stiffness for Compliant and Effective Grasping.
Wang, Wei; Ahn, Sung-Hoon
2017-12-01
Soft pneumatic actuators and motor-based mechanisms being concomitant with the cumbersome appendages have many challenges to making the independent robotic system with compact and lightweight configuration. Meanwhile, shape memory actuators have shown a promising alternative solution in many engineering applications ranging from artificial muscle to aerospace industry. However, one of the main limitations of such systems is their inherent softness resulting in a small actuation force, which prevents them from more effective applications. This issue can be solved by combining shape memory actuators and the mechanism of stiffness modulation. As a first, this study describes a shape memory alloy-based soft gripper composed of three identical fingers with variable stiffness for adaptive grasping in low stiffness state and effective holding in high stiffness state. Each finger with two hinges is fabricated through integrating soft composite actuator with stiffness changeable material where each hinge can approximately achieve a 55-fold changeable stiffness independently. Besides, each finger with two hinges can actively achieve multiple postures by both selectively changing the stiffness of hinges and actuating the relevant SMA wire. Based on these principles, the gripper is applicable for grasping objects with deformable shapes and varying shapes with a large range of weight where its maximum grasping force is increased to ∼10 times through integrating with the stiffness changeable mechanism. The final demonstration shows that the finger with desired shape-retained configurations enables the gripper to successfully pick up a frustum-shaped object.
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A combined piezoelectric composite actuator and its application to wing/blade tips
NASA Astrophysics Data System (ADS)
Ha, Kwangtae
A novel combined piezoelectric-composite actuator configuration is proposed and analytically modeled in this work. The actuator is a low complexity, active compliant mechanism obtained by coupling a modified star cross sectional configuration composite beam with a helicoidal bimorph piezoelectric actuator coiled around it. This novel actuator is a good candidate as a hinge tension-torsion bar actuator for a helicopter rotor blade flap or blade tip and mirror rotational positioning. In the wing tip case, the tip deflection angle is different only according to the aerodynamic moment depending on the hinge position of the actuator along the chord and applied voltage because there is no centrifugal force. For an active blade tip subject to incompressible flow and 2D quasi steady airloads, its twist angle is related not only to aerodynamic moment and applied voltage but also to coupling terms, such as the trapeze effect and the tennis racquet effect. Results show the benefit of hinge position aft of the aerodynamic center, such that the blade tip response is amplified by airloads. Contrary to this effect, results also show that the centrifugal effects and inertial effect cause an amplitude reduction in the response. Summation of these effects determines the overall blade tip response. The results for a certain hinge position of Xh=1.5% chord aft of the quarter chord point proves that the tip deflection target design range of beta ∈ [-2,+2] can be achieved for all pitch angle configurations chosen.
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Xiao, Xiaolin; Moreno-Moral, Aida; Rotival, Maxime; Bottolo, Leonardo; Petretto, Enrico
2014-01-01
Recent high-throughput efforts such as ENCODE have generated a large body of genome-scale transcriptional data in multiple conditions (e.g., cell-types and disease states). Leveraging these data is especially important for network-based approaches to human disease, for instance to identify coherent transcriptional modules (subnetworks) that can inform functional disease mechanisms and pathological pathways. Yet, genome-scale network analysis across conditions is significantly hampered by the paucity of robust and computationally-efficient methods. Building on the Higher-Order Generalized Singular Value Decomposition, we introduce a new algorithmic approach for efficient, parameter-free and reproducible identification of network-modules simultaneously across multiple conditions. Our method can accommodate weighted (and unweighted) networks of any size and can similarly use co-expression or raw gene expression input data, without hinging upon the definition and stability of the correlation used to assess gene co-expression. In simulation studies, we demonstrated distinctive advantages of our method over existing methods, which was able to recover accurately both common and condition-specific network-modules without entailing ad-hoc input parameters as required by other approaches. We applied our method to genome-scale and multi-tissue transcriptomic datasets from rats (microarray-based) and humans (mRNA-sequencing-based) and identified several common and tissue-specific subnetworks with functional significance, which were not detected by other methods. In humans we recapitulated the crosstalk between cell-cycle progression and cell-extracellular matrix interactions processes in ventricular zones during neocortex expansion and further, we uncovered pathways related to development of later cognitive functions in the cortical plate of the developing brain which were previously unappreciated. Analyses of seven rat tissues identified a multi-tissue subnetwork of co-expressed heat shock protein (Hsp) and cardiomyopathy genes (Bag3, Cryab, Kras, Emd, Plec), which was significantly replicated using separate failing heart and liver gene expression datasets in humans, thus revealing a conserved functional role for Hsp genes in cardiovascular disease.
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Interleukin-11 binds specific EF-hand proteins via their conserved structural motifs.
Kazakov, Alexei S; Sokolov, Andrei S; Vologzhannikova, Alisa A; Permyakova, Maria E; Khorn, Polina A; Ismailov, Ramis G; Denessiouk, Konstantin A; Denesyuk, Alexander I; Rastrygina, Victoria A; Baksheeva, Viktoriia E; Zernii, Evgeni Yu; Zinchenko, Dmitry V; Glazatov, Vladimir V; Uversky, Vladimir N; Mirzabekov, Tajib A; Permyakov, Eugene A; Permyakov, Sergei E
2017-01-01
Interleukin-11 (IL-11) is a hematopoietic cytokine engaged in numerous biological processes and validated as a target for treatment of various cancers. IL-11 contains intrinsically disordered regions that might recognize multiple targets. Recently we found that aside from IL-11RA and gp130 receptors, IL-11 interacts with calcium sensor protein S100P. Strict calcium dependence of this interaction suggests a possibility of IL-11 interaction with other calcium sensor proteins. Here we probed specificity of IL-11 to calcium-binding proteins of various types: calcium sensors of the EF-hand family (calmodulin, S100B and neuronal calcium sensors: recoverin, NCS-1, GCAP-1, GCAP-2), calcium buffers of the EF-hand family (S100G, oncomodulin), and a non-EF-hand calcium buffer (α-lactalbumin). A specific subset of the calcium sensor proteins (calmodulin, S100B, NCS-1, GCAP-1/2) exhibits metal-dependent binding of IL-11 with dissociation constants of 1-19 μM. These proteins share several amino acid residues belonging to conservative structural motifs of the EF-hand proteins, 'black' and 'gray' clusters. Replacements of the respective S100P residues by alanine drastically decrease its affinity to IL-11, suggesting their involvement into the association process. Secondary structure and accessibility of the hinge region of the EF-hand proteins studied are predicted to control specificity and selectivity of their binding to IL-11. The IL-11 interaction with the EF-hand proteins is expected to occur under numerous pathological conditions, accompanied by disintegration of plasma membrane and efflux of cellular components into the extracellular milieu.
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Bubis, José; Martínez, Juan Carlos; Calabokis, Maritza; Ferreira, Joilyneth; Sanz-Rodríguez, Carlos E; Navas, Victoria; Escalona, José Leonardo; Guo, Yurong; Taylor, Susan S
2018-03-01
The full gene sequence encoding for the Trypanosoma equiperdum ortholog of the cAMP-dependent protein kinase (PKA) regulatory (R) subunits was cloned. A poly-His tagged construct was generated [TeqR-like(His) 8 ], and the protein was expressed in bacteria and purified to homogeneity. The size of the purified TeqR-like(His) 8 was determined to be ∼57,000 Da by molecular exclusion chromatography indicating that the parasite protein is a monomer. Limited proteolysis with various proteases showed that the T. equiperdum R-like protein possesses a hinge region very susceptible to proteolysis. The recombinant TeqR-like(His) 8 did not bind either [ 3 H] cAMP or [ 3 H] cGMP up to concentrations of 0.40 and 0.65 μM, respectively, and neither the parasite protein nor its proteolytically generated carboxy-terminal large fragments were capable of binding to a cAMP-Sepharose affinity column. Bioinformatics analyses predicted that the carboxy-terminal region of the trypanosomal R-like protein appears to fold similarly to the analogous region of all known PKA R subunits. However, the protein amino-terminal portion seems to be unrelated and shows homology with proteins that contained Leu-rich repeats, a folding motif that is particularly appropriate for protein-protein interactions. In addition, the three-dimensional structure of the T. equiperdum protein was modeled using the crystal structure of the bovine PKA R I α subunit as template. Molecular docking experiments predicted critical changes in the environment of the two putative nucleotide binding clefts of the parasite protein, and the resulting binding energy differences support the lack of cyclic nucleotide binding in the trypanosomal R-like protein. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.
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Findeisen, Felix; Linder, Jürgen U; Schultz, Anita; Schultz, Joachim E; Brügger, Britta; Wieland, Felix; Sinning, Irmgard; Tews, Ivo
2007-06-22
The universal secondary messenger cAMP is produced by adenylyl cyclases (ACs). Most bacterial and all eukaryotic ACs belong to class III of six divergent classes. A class III characteristic is formation of the catalytic pocket at a dimer interface and the presence of additional regulatory domains. Mycobacterium tuberculosis possesses 15 class III ACs, including Rv1264, which is activated at acidic pH due to pH-dependent structural transitions of the Rv1264 dimer. It has been shown by X-ray crystallography that the N-terminal regulatory and C-terminal catalytic domains of Rv1264 interact in completely different ways in the active and inhibited states. Here, we report an in-depth structural and functional analysis of the regulatory domain of Rv1264. The 1.6 A resolution crystal structure shows the protein in a tight, disk-shaped dimer, formed around a helical bundle, and involving a protein chain crossover. To understand pH regulation, we determined structures at acidic and basic pH values and employed structure-based mutagenesis in the holoenzyme to elucidate regulation using an AC activity assay. It has been shown that regulatory and catalytic domains must be linked in a single protein chain. The new studies demonstrate that the length of the linker segment is decisive for regulation. Several amino acids on the surface of the regulatory domain, when exchanged, altered the pH-dependence of AC activity. However, these residues are not conserved amongst a number of related ACs. The closely related mycobacterial Rv2212, but not Rv1264, is strongly activated by the addition of fatty acids. The structure resolved the presence of a deeply embedded fatty acid, characterised as oleic acid by mass spectrometry, which may serve as a hinge. From these data, we conclude that the regulatory domain is a structural scaffold used for distinct regulatory purposes.
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Concepts, characterization, and modeling of MEMS microswitches with gold contacts in MUMPs
NASA Astrophysics Data System (ADS)
Lafontan, Xavier; Dufaza, Christian; Robert, Michel; Pressecq, Francis; Perez, Guy
2001-04-01
This paper demonstrates that RF MEMS micro-switches can be realized with a low cost MEMS technology such as MUMPs. Two different switches are proposed, namely the hinged beam switch and the gold overflowing switch. Their concepts, design and characterization are described in details. On-resistance as low as 5 - 6 (Omega) for the gold overflowing switch and 2 - 3 (Omega) for the hinged beam switch have been measured. Finally, experimental measurements showed that force and electrical current had strong influences on the overall electrical contact.
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NASA Astrophysics Data System (ADS)
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.
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Thermoelectric generator with hinged assembly for fins
Purdy, David L.; Shapiro, Zalman M.; Hursen, Thomas F.; Maurer, Gerould W.
1976-11-02
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.
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Aerodynamic characteristics of horizontal tail surfaces
NASA Technical Reports Server (NTRS)
Silverstein, Abe; Katzoff, S
1940-01-01
Collected data are presented on the aerodynamic characteristics of 17 horizontal tail surfaces including several with balanced elevators and two with end plates. Curves are given for coefficients of normal force, drag, and elevator hinge moment. A limited analysis of the results has been made. The normal-force coefficients are in better agreement with the lifting-surface theory of Prandtl and Blenk for airfoils of low aspect ratio than with the usual lifting-line theory. Only partial agreement exists between the elevator hinge-moment coefficients and those predicted by Glauert's thin-airfoil theory.
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Simplified Flutter Prevention Criteria for Personal Type Aircraft
1955-01-01
Play of Ailerons The total free play at the aileron edge of each aileron, when the other aileron is cla:nped to the wing should not exceed 2.5 percent of...the aileron chcrd aft of the hinge line at the station where the free play is measured. Elevator Balance Each elevator should be dynamically balanced...8217•. • . e •% f% ’dr-,•~~ • . S•, ,,,8- 2. The total free play at the tab trailing edge should be less than 2.5% of the tab chord aft of the hinge
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Process of making medical clip
NASA Technical Reports Server (NTRS)
Baucom, R. M. (Inventor)
1984-01-01
An X-ray transparent and biologically inert medical clip for treating aneurisms and the like is disclosed, as well as a process for its production. A graphite reinforced composite film is molded into a unitary structure having a pair of hourglass-like cavities which are hinged together with a pair of jaws for grasping the aneurism extending from the wall of one cavity. A silicone rubber pellet is disposed in the other cavity to exert a spring force through the hinge area to normally bias the jaws into contact with each other.
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Spasticity management in multiple sclerosis.
Hughes, Christina; Howard, Ileana M
2013-11-01
Spasticity is a prevalent and potentially disabling symptom common in individuals with multiple sclerosis. Adequate evaluation and management of spasticity requires a careful assessment of the patient's history to determine functional impact of spasticity and potential exacerbating factors, and physical examination to determine the extent of the condition and culpable muscles. A host of options for spasticity management are available: therapeutic exercise, physical modalities, complementary/alternative medicine interventions, oral medications, chemodenervation, and implantation of an intrathecal baclofen pump. Choice of treatment hinges on a combination of the extent of symptoms, patient preference, and availability of services. Copyright © 2013 Elsevier Inc. All rights reserved.
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Integrated optimization of nonlinear R/C frames with reliability constraints
NASA Technical Reports Server (NTRS)
Soeiro, Alfredo; Hoit, Marc
1989-01-01
A structural optimization algorithm was researched including global displacements as decision variables. The algorithm was applied to planar reinforced concrete frames with nonlinear material behavior submitted to static loading. The flexural performance of the elements was evaluated as a function of the actual stress-strain diagrams of the materials. Formation of rotational hinges with strain hardening were allowed and the equilibrium constraints were updated accordingly. The adequacy of the frames was guaranteed by imposing as constraints required reliability indices for the members, maximum global displacements for the structure and a maximum system probability of failure.
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Kocsis, E; Trus, B L; Steer, C J; Bisher, M E; Steven, A C
1991-08-01
We have developed computational techniques that allow image averaging to be applied to electron micrographs of filamentous molecules that exhibit tight and variable curvature. These techniques, which involve straightening by cubic-spline interpolation, image classification, and statistical analysis of the molecules' curvature properties, have been applied to purified brain clathrin. This trimeric filamentous protein polymerizes, both in vivo and in vitro, into a wide range of polyhedral structures. Contrasted by low-angle rotary shadowing, dissociated clathrin molecules appear as distinctive three-legged structures, called "triskelions" (E. Ungewickell and D. Branton (1981) Nature 289, 420). We find triskelion legs to vary from 35 to 62 nm in total length, according to an approximately bell-shaped distribution (mu = 51.6 nm). Peaks in averaged curvature profiles mark hinges or sites of enhanced flexibility. Such profiles, calculated for each length class, show that triskelion legs are flexible over their entire lengths. However, three curvature peaks are observed in every case: their locations define a proximal segment of systematically increasing length (14.0-19.0 nm), a mid-segment of fixed length (approximately 12 nm), and a rather variable end-segment (11.6-19.5 nm), terminating in a hinge just before the globular terminal domain (approximately 7.3 nm diameter). Thus, two major factors contribute to the overall variability in leg length: (1) stretching of the proximal segment and (2) stretching of the end-segment and/or scrolling of the terminal domain. The observed elasticity of the proximal segment may reflect phosphorylation of the clathrin light chains.
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Endrizzi, James A; Beernink, Peter T
2017-11-01
A classical model for allosteric regulation of enzyme activity posits an equilibrium between inactive and active conformations. An alternative view is that allosteric activation is achieved by increasing the potential for conformational changes that are essential for catalysis. In the present study, substitution of a basic residue in the active site of the catalytic (C) trimer of aspartate transcarbamoylase with a non-polar residue results in large interdomain hinge changes in the three chains of the trimer. One conformation is more open than the chains in both the wild-type C trimer and the catalytic chains in the holoenzyme, the second is closed similar to the bisubstrate-analog bound conformation and the third hinge angle is intermediate to the other two. The active-site 240s loop conformation is very different between the most open and closed chains, and is disordered in the third chain, as in the holoenzyme. We hypothesize that binding of anionic substrates may promote similar structural changes. Further, the ability of the three catalytic chains in the trimer to access the open and closed active-site conformations simultaneously suggests a cyclic catalytic mechanism, in which at least one of the chains is in an open conformation suitable for substrate binding whereas another chain is closed for catalytic turnover. Based on the many conformations observed for the chains in the isolated catalytic trimer to date, we propose that allosteric activation of the holoenzyme occurs by release of quaternary constraint into an ensemble of active-site conformations. © 2017 The Protein Society.
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IgY: a key isotype in antibody evolution.
Zhang, Xiaoying; Calvert, Rosaleen A; Sutton, Brian J; Doré, Katy A
2017-11-01
Immunoglobulin Y (IgY) is central to our understanding of immunoglobulin evolution. It has links to antibodies from the ancestral IgM to the mucosal IgX and IgA, as well as to mammalian serum IgG and IgE. IgY is found in amphibians, birds and reptiles, and as their most abundant serum antibody, is orthologous to mammalian IgG. However, IgY has the same domain architecture as IgM and IgE, lacking a hinge region and comprising four heavy-chain constant domains. The relationship between IgY and the mucosal antibodies IgX and IgA is discussed herein, in particular the question of how IgA could have contributed to the emergence of IgY. Although IgY does not contain a hinge region, amphibian IgF and duck-billed platypus IgY/O, which are closely related to IgY, do contain this region, as does mammalian IgG, IgA and IgD. A hinge region must therefore have evolved at least three times independently by convergent evolution. In the absence of three-dimensional structural information for the complete Fc fragment of chicken IgY (IgY-Fc), it remains to be discovered whether IgY displays the same conformational properties as IgM and IgE, which exhibit substantial flexibility in their Fc regions. IgY has three characterised Fc receptors, chicken Ig-like receptor AB1 (CHIR-AB1), the chicken yolk sac IgY receptor (FcRY) and Gallus gallus Fc receptor (ggFcR). These receptors bind to IgY at sites that are structurally homologous to mammalian counterparts; IgA/FcαRI for CHIR-AB1, IgG/FcRn for FcRY and IgE/FcϵRI and IgG/FcγR for ggFcR. These resemblances reflect the close evolutionary relationships between IgY and IgA, IgG and IgE. However, the evolutionary distance between birds and mammals allows for the ready generation of IgY antibodies to conserved mammalian proteins for medical and biotechnological applications. Furthermore, the lack of reactivity of IgY with mammalian Fc receptors, and the fact that large quantities of IgY can be made quickly and cheaply in chicken eggs, offers important advantages and considerable potential for IgY in research, diagnostics and therapeutics. © 2017 Cambridge Philosophical Society.
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Pinto, João; Gribaldo, Simonetta; Legrand, Eric; Niang, Makhtar; Kim, Nimol; Pharath, Lim; Volnay, Béatrice; Ekala, Marie Therese; Bouchier, Christiane; Fandeur, Thierry; Berzosa, Pedro; Benito, Agustin; Ferreira, Isabel Dinis; Ferreira, Cynthia; Vieira, Pedro Paulo; Alecrim, Maria das Graças; Mercereau-Puijalon, Odile; Cravo, Pedro
2010-01-01
Artemisinin, a thapsigargin-like sesquiterpene has been shown to inhibit the Plasmodium falciparum sarco/endoplasmic reticulum calcium-ATPase PfSERCA. To collect baseline pfserca sequence information before field deployment of Artemisinin-based Combination therapies that may select mutant parasites, we conducted a sequence analysis of 100 isolates from multiple sites in Africa, Asia and South America. Coding sequence diversity was large, with 29 mutated codons, including 32 SNPs (average of one SNP/115 bp), of which 19 were novel mutations. Most SNP detected in this study were clustered within a region in the cytosolic head of the protein. The PfSERCA functional domains were very well conserved, with non synonymous mutations located outside the functional domains, except for the S769N mutation associated in French Guiana with elevated IC50 for artemether. The S769N mutation is located close to the hinge of the headpiece, which in other species modulates calcium affinity and in consequence efficacy of inhibitors, possibly linking calcium homeostasis to drug resistance. Genetic diversity was highest in Senegal, Brazil and French Guiana, and few mutations were identified in Asia. Population genetic analysis was conducted for a partial fragment of the gene encompassing nucleotide coordinates 87-2862 (unambiguous sequence available for 96 isolates). This supported a geographic clustering, with a separation between Old and New World samples and one dominant ancestral haplotype. Genetic drift alone cannot explain the observed polymorphism, suggesting that other evolutionary mechanisms are operating. One possible contributor could be the frequency of haemoglobinopathies that are associated with calcium dysregulation in the erythrocyte. PMID:20195531
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Modeling and design of a high-performance hybrid actuator
NASA Astrophysics Data System (ADS)
Aloufi, Badr; Behdinan, Kamran; Zu, Jean
2016-12-01
This paper presents the model and design of a novel hybrid piezoelectric actuator which provides high active and passive performances for smart structural systems. The actuator is composed of a pair of curved pre-stressed piezoelectric actuators, so-called commercially THUNDER actuators, installed opposite each other using two clamping mechanisms constructed of in-plane fixable hinges, grippers and solid links. A fully mathematical model is developed to describe the active and passive dynamics of the actuator and investigate the effects of its geometrical parameters on the dynamic stiffness, free displacement and blocked force properties. Among the literature that deals with piezoelectric actuators in which THUNDER elements are used as a source of electromechanical power, the proposed study is unique in that it presents a mathematical model that has the ability to predict the actuator characteristics and achieve other phenomena, such as resonances, mode shapes, phase shifts, dips, etc. For model validation, the measurements of the free dynamic response per unit voltage and passive acceleration transmissibility of a particular actuator design are used to check the accuracy of the results predicted by the model. The results reveal that there is a good agreement between the model and experiment. Another experiment is performed to teste the linearity of the actuator system by examining the variation of the output dynamic responses with varying forces and voltages at different frequencies. From the results, it can be concluded that the actuator acts approximately as a linear system at frequencies up to 1000 Hz. A parametric study is achieved here by applying the developed model to analyze the influence of the geometrical parameters of the fixable hinges on the active and passive actuator properties. The model predictions in the frequency range of 0-1000 Hz show that the hinge thickness, radius, and opening angle parameters have great effects on the frequency dynamic responses, passive isolation characteristics and the locations of their peaks and dips. Furthermore, the output actuating force can be improved by increasing the hinge hardness, which is controlled by its dimensions, although increasing the hinge hardness may cause a decrease in the free displacement and passive insulation performance, particularly at low frequencies.
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McNicholl, E. Tyler; Das, Rahul; SilDas, Soumita; Taylor, Susan S.; Melacini, Giuseppe
2010-01-01
Protein kinase A (PKA) is the main receptor for the universal cAMP second messenger. PKA is a tetramer with two catalytic (C) and two regulatory (R) subunits, each including two tandem cAMP binding domains, i.e. CBD-A and -B. Structural investigations of RIα have revealed that although CBD-A plays a pivotal role in the cAMP-dependent inhibition of C, the main function of CBD-B is to regulate the access of cAMP to site A. To further understand the mechanism underlying the cross-talk between CBD-A and -B, we report here the NMR investigation of a construct of R, RIα-(119–379), which unlike previous fragments characterized by NMR, spans in full both CBDs. Our NMR studies were also extended to two mutants, R209K and the corresponding R333K, which severely reduce the affinity of cAMP for CBD-A and -B, respectively. The comparative NMR analysis of wild-type RIα-(119–379) and of the two domain silencing mutations has led to the definition at an unprecedented level of detail of both intra- and interdomain allosteric networks, revealing several striking differences between the two CBDs. First, the two domains, although homologous in sequence and structure, exhibit remarkably different responses to the R/K mutations especially at the β2-3 allosteric “hot spot.” Second, although the two CBDs are reciprocally coupled at the level of local unfolding of the hinge, the A-to-B and B-to-A pathways are dramatically asymmetrical at the level of global unfolding. Such an asymmetric interdomain cross-talk ensures efficiency and robustness in both the activation and de-activation of PKA. PMID:20202931
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Assembly of human C-terminal binding protein (CtBP) into tetramers.
Bellesis, Andrew G; Jecrois, Anne M; Hayes, Janelle A; Schiffer, Celia A; Royer, William E
2018-06-08
C-terminal binding protein 1 (CtBP1) and CtBP2 are transcriptional coregulators that repress numerous cellular processes, such as apoptosis, by binding transcription factors and recruiting chromatin-remodeling enzymes to gene promoters. The NAD(H)-linked oligomerization of human CtBP is coupled to its co-transcriptional activity, which is implicated in cancer progression. However, the biologically relevant level of CtBP assembly has not been firmly established; nor has the stereochemical arrangement of the subunits above that of a dimer. Here, multi-angle light scattering (MALS) data established the NAD + - and NADH-dependent assembly of CtBP1 and CtBP2 into tetramers. An examination of subunit interactions within CtBP1 and CtBP2 crystal lattices revealed that both share a very similar tetrameric arrangement resulting from assembly of two dimeric pairs, with specific interactions probably being sensitive to NAD(H) binding. Creating a series of mutants of both CtBP1 and CtBP2, we tested the hypothesis that the crystallographically observed interdimer pairing stabilizes the solution tetramer. MALS data confirmed that these mutants disrupt both CtBP1 and CtBP2 tetramers, with the dimer generally remaining intact, providing the first stereochemical models for tetrameric assemblies of CtBP1 and CtBP2. The crystal structure of a subtle destabilizing mutant suggested that small structural perturbations of the hinge region linking the substrate- and NAD-binding domains are sufficient to weaken the CtBP1 tetramer. These results strongly suggest that the tetramer is important in CtBP function, and the series of CtBP mutants reported here can be used to investigate the physiological role of the tetramer. © 2018 Bellesis et al.
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Monaco, Giovanni; Decrock, Elke; Nuyts, Koen; Wagner, Larry E; Luyten, Tomas; Strelkov, Sergei V; Missiaen, Ludwig; De Borggraeve, Wim M; Leybaert, Luc; Yule, David I; De Smedt, Humbert; Parys, Jan B; Bultynck, Geert
2013-01-01
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.
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Nanobody Binding to a Conserved Epitope Promotes Norovirus Particle Disassembly
Koromyslova, Anna D.
2014-01-01
ABSTRACT Human noroviruses are icosahedral single-stranded RNA viruses. The capsid protein is divided into shell (S) and protruding (P) domains, which are connected by a flexible hinge region. There are numerous genetically and antigenically distinct noroviruses, and the dominant strains evolve every other year. Vaccine and antiviral development is hampered by the difficulties in growing human norovirus in cell culture and the continually evolving strains. Here, we show the X-ray crystal structures of human norovirus P domains in complex with two different nanobodies. One nanobody, Nano-85, was broadly reactive, while the other, Nano-25, was strain specific. We showed that both nanobodies bound to the lower region on the P domain and had nanomolar affinities. The Nano-85 binding site mainly comprised highly conserved amino acids among the genetically distinct genogroup II noroviruses. Several of the conserved residues also were recognized by a broadly reactive monoclonal antibody, which suggested this region contained a dominant epitope. Superposition of the P domain nanobody complex structures into a cryoelectron microscopy particle structure revealed that both nanobodies bound at occluded sites on the particles. The flexible hinge region, which contained ∼10 to 12 amino acids, likely permitted a certain degree of P domain movement on the particles in order to accommodate the nanobodies. Interestingly, the Nano-85 binding interaction with intact particles caused the particles to disassemble in vitro. Altogether, these results suggested that the highly conserved Nano-85 binding epitope contained a trigger mechanism for particle disassembly. Principally, this epitope represents a potential site of norovirus vulnerability. IMPORTANCE We characterized two different nanobodies (Nano-85 and Nano-25) that bind to human noroviruses. Both nanobodies bound with high affinities to the lower region of the P domain, which was occluded on intact particles. Nano-25 was specific for GII.10, whereas Nano-85 bound several different GII genotypes, including GII.4, GII.10, and GII.12. We showed that Nano-85 was able to detect norovirus virions in clinical stool specimens using a sandwich enzyme-linked immunosorbent assay. Importantly, we found that Nano-85 binding to intact particles caused the particles to disassemble. We believe that with further testing, Nano-85 not only will work as a diagnostic reagent in norovirus detection systems but also could function as a broadly reactive GII norovirus antiviral. PMID:25520510
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NASA Astrophysics Data System (ADS)
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.
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Traverse, Charles C; Ochman, Howard
2017-08-29
Advances in sequencing technologies have enabled direct quantification of genome-wide errors that occur during RNA transcription. These errors occur at rates that are orders of magnitude higher than rates during DNA replication, but due to technical difficulties such measurements have been limited to single-base substitutions and have not yet quantified the scope of transcription insertions and deletions. Previous reporter gene assay findings suggested that transcription indels are produced exclusively by elongation complex slippage at homopolymeric runs, so we enumerated indels across the protein-coding transcriptomes of Escherichia coli and Buchnera aphidicola , which differ widely in their genomic base compositions and incidence of repeat regions. As anticipated from prior assays, transcription insertions prevailed in homopolymeric runs of A and T; however, transcription deletions arose in much more complex sequences and were rarely associated with homopolymeric runs. By reconstructing the relocated positions of the elongation complex as inferred from the sequences inserted or deleted during transcription, we show that continuation of transcription after slippage hinges on the degree of nucleotide complementarity within the RNA:DNA hybrid at the new DNA template location. IMPORTANCE The high level of mistakes generated during transcription can result in the accumulation of malfunctioning and misfolded proteins which can alter global gene regulation and in the expenditure of energy to degrade these nonfunctional proteins. The transcriptome-wide occurrence of base substitutions has been elucidated in bacteria, but information on transcription insertions and deletions-errors that potentially have more dire effects on protein function-is limited to reporter gene constructs. Here, we capture the transcriptome-wide spectrum of insertions and deletions in Escherichia coli and Buchnera aphidicola and show that they occur at rates approaching those of base substitutions. Knowledge of the full extent of sequences subject to transcription indels supports a new model of bacterial transcription slippage, one that relies on the number of complementary bases between the transcript and the DNA template to which it slipped. Copyright © 2017 Traverse and Ochman.
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Casali, Monica; Banta, Scott; Zambonelli, Carlo; Megeed, Zaki; Yarmush, Martin L
2008-06-01
Environmentally responsive proteins and peptides are increasingly finding utility in various engineered systems due to their ability to respond to the presentation of external stimuli. A classic example of this behavior is the influenza hemagglutinin (HA) fusion protein. At neutral pH, HA exists in a non-fusogenic state, but upon exposure to low pH, the conformation of the structure changes to expose a fusogenic peptide. During this structural change, massive rearrangements occur in a subunit of HA (HA2). Crystallography data has shown that a loop of 28 amino acids (residues 54-81) undergoes a dramatic transition from a random coil to an alpha-helix. This segment connects to two flanking helical regions (short and long) to form a long, continuous helix. Here, we report the results of site-directed mutagenesis study on LOOP-36 to further understand the mechanism of this important stimulus-responsive peptide. The conformational transition of a bacterially expressed LOOP-36 was found to be less dramatic than has been previously reported. The systematic mutation of glutamate and histidine residues in the peptide to glutamines (glutamine scanning) did not impact the conformational behavior of the peptide, but the substitution of the glycine residue at position 22 with alanine resulted in significant pH-responsive behavior. Therefore this mutant stimulus-responsive peptide may be more valuable for future protein engineering and bionanotechnology efforts.
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2014-01-01
Background The advent of human genome sequencing project has led to a spurt in the number of protein sequences in the databanks. Success of structure based drug discovery severely hinges on the availability of structures. Despite significant progresses in the area of experimental protein structure determination, the sequence-structure gap is continually widening. Data driven homology based computational methods have proved successful in predicting tertiary structures for sequences sharing medium to high sequence similarities. With dwindling similarities of query sequences, advanced homology/ ab initio hybrid approaches are being explored to solve structure prediction problem. Here we describe Bhageerath-H, a homology/ ab initio hybrid software/server for predicting protein tertiary structures with advancing drug design attempts as one of the goals. Results Bhageerath-H web-server was validated on 75 CASP10 targets which showed TM-scores ≥0.5 in 91% of the cases and Cα RMSDs ≤5Å from the native in 58% of the targets, which is well above the CASP10 water mark. Comparison with some leading servers demonstrated the uniqueness of the hybrid methodology in effectively sampling conformational space, scoring best decoys and refining low resolution models to high and medium resolution. Conclusion Bhageerath-H methodology is web enabled for the scientific community as a freely accessible web server. The methodology is fielded in the on-going CASP11 experiment. PMID:25521245
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Cysteine Racemization on IgG Heavy and Light Chains
Zhang, Qingchun; Flynn, Gregory C.
2013-01-01
Under basic pH conditions, the heavy chain 220-light chain 214 (H220-L214) disulfide bond, found in the flexible hinge region of an IgG1, can convert to a thioether. Similar conditions also result in racemization of the H220 cysteine. Here, we report that racemization occurs on both H220 and L214 on an IgG1 with a λ light chain (IgG1λ) but almost entirely on H220 of an IgGl with a κ light chain (IgG1κ) under similar conditions. Likewise, racemization was detected at significant levels on H220 and L214 on endogenous human IgG1λ but only at the H220 position on IgG1κ. Low but measurable levels of d-cysteines were found on IgG2 cysteines in the hinge region, both with monoclonal antibodies incubated under basic pH conditions and on antibodies isolated from human serum. A simplified reaction mechanism involving reversible β-elimination on the cysteine is presented that accounts for both base-catalyzed racemization and thioether formation at the hinge disulfide. PMID:24142697
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NASA Technical Reports Server (NTRS)
Aoyagi, Kiyoshi; Hickey, David H.
1959-01-01
Previous investigations have shown that increased blowing at the hinge-line radius of a plain flap will give flap lift increases above that realized with boundary-layer control. Other experiments and theory have shown that blowing from a wing trailing edge, through the jet flap effect, produced lift increases. The present investigation was made to determine whether blowing simultaneously at the hinge-line radius and trailing edge would be more effective than blowing separately at either location. The tests were made at a Reynolds number of 4.5 x 10(exp 6) with a 35 deg sweptback-wing airplane. For this report, only the lift data are presented. Of the three flap blowing arrangements tested, blowing distributed between the trailing edge and the hinge-line radius of a plain flap was found to be superior to blowing at either location separately at the plain flap deflections of interest. Comparison of estimated and experimental jet flap effectiveness was fair.
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How does a woodpecker work? An impact dynamics approach
NASA Astrophysics Data System (ADS)
Liu, Yuzhe; Qiu, Xinming; Yu, Tongxi; Tao, Jiawei; Cheng, Ze
2015-04-01
To understand how a woodpecker is able accelerate its head to such a high velocity in a short amount of time, a multi-rigid-segment model of a woodpecker's body is established in this study. Based on the skeletal specimen of the woodpecker and several videos of woodpeckers pecking, the parameters of a three-degree-of-freedom system are determined. The high velocity of the head is found to be the result of a whipping effect, which could be affected by muscle torque and tendon stiffness. The mechanism of whipping is analyzed by comparing the response of a hinged rod to that of a rigid rod. Depending on the parameters, the dynamic behavior of a hinged rod is classified into three response modes. Of these, a high free-end velocity could be achieved in mode II. The model is then generalized to a multihinge condition, and the free-end velocity is found to increase with hinge number, which explains the high free-end velocity resulting from whipping. Furthermore, the effects of some other factors, such as damping and mass distribution, on the velocity are also discussed.
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NASA Technical Reports Server (NTRS)
Hughes, M. T.; Mennell, R. C.
1974-01-01
Experimental aerodynamic investigations were conducted on an 0.015-scale representation of the integrated space shuttle launch vehicle in the trisonic wind tunnel. The primary test objective was to obtain subsonic and transonic elevon and bodyflap hinge moments and wing bending-torsion moments in the presence of the launch vehicle. Wing pressures were also recorded for the upper and lower right wing surfaces at two spanwise stations. The hinge moment, wing bending/torsion moments and wing pressure data were recorded over an angle-of-attack (alpha) range from -8 deg to +8 deg, and angle-of-sideslip (beta) range from -8 deg to +8 deg and at Mach numbers of 0.90, 1.12, 1.24 and 1.50. Tests were also conducted to determine the effects of the orbiter rear attach cross beam and the forward attach wedge and strut diameter. The orbiter alone was tested at 0.90 and 1.24 Mach number only.
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NASA Technical Reports Server (NTRS)
Herman, G. C.
1986-01-01
A lateral guidance algorithm which controls the location of the line of intersection between the actual and desired orbital planes (the hinge line) is developed for the aerobraking phase of a lift-modulated orbital transfer vehicle. The on-board targeting algorithm associated with this lateral guidance algorithm is simple and concise which is very desirable since computation time and space are limited on an on-board flight computer. A variational equation which describes the movement of the hinge line is derived. Simple relationships between the plane error, the desired hinge line position, the position out-of-plane error, and the velocity out-of-plane error are found. A computer simulation is developed to test the lateral guidance algorithm for a variety of operating conditions. The algorithm does reduce the total burn magnitude needed to achieve the desired orbit by allowing the plane correction and perigee-raising burn to be combined in a single maneuver. The algorithm performs well under vacuum perigee dispersions, pot-hole density disturbance, and thick atmospheres. The results for many different operating conditions are presented.
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Qin, Guangzhao; Yan, Qing-Bo; Qin, Zhenzhen; Yue, Sheng-Ying; Cui, Hui-Juan; Zheng, Qing-Rong; Su, Gang
2014-01-01
We systematically investigated the geometric, electronic and thermoelectric (TE) properties of bulk black phosphorus (BP) under strain. The hinge-like structure of BP brings unusual mechanical responses such as anisotropic Young's modulus and negative Poisson's ratio. A sensitive electronic structure of BP makes it transform among metal, direct and indirect semiconductors under strain. The maximal figure of merit ZT of BP is found to be 0.72 at 800 K that could be enhanced to 0.87 by exerting an appropriate strain, revealing BP could be a potential medium-high temperature TE material. Such strain-induced enhancements of TE performance are often observed to occur at the boundary of the direct-indirect band gap transition, which can be attributed to the increase of degeneracy of energy valleys at the transition point. By comparing the structure of BP with SnSe, a family of potential TE materials with hinge-like structure are suggested. This study not only exposes various novel properties of BP under strain, but also proposes effective strategies to seek for better TE materials. PMID:25374306
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The PIM kinases in hematological cancers.
Alvarado, Yesid; Giles, Francis J; Swords, Ronan T
2012-02-01
The PIM genes represent a family of proto-oncogenes that encode three different serine/threonine protein kinases (PIM1, PIM2 and PIM3) with essential roles in the regulation of signal transduction cascades, which promote cell survival, proliferation and drug resistance. PIM kinases are overexpressed in several hematopoietic tumors and support in vitro and in vivo malignant cell growth and survival, through cell cycle regulation and inhibition of apoptosis. PIM kinases do not have an identified regulatory domain, which means that these proteins are constitutively active once transcribed. They appear to be critical downstream effectors of important oncoproteins and, when overexpressed, can mediate drug resistance to available agents, such as rapamycin. Recent crystallography studies reveal that, unlike other kinases, they possess a hinge region, which creates a unique binding pocket for ATP, offering a target for an increasing number of potent small-molecule PIM kinase inhibitors. Preclinical studies in models of various hematologic cancers indicate that these novel agents show promising activity and some of them are currently being evaluated in a clinical setting. In this review, we profile the PIM kinases as targets for therapeutics in hematologic malignancies.
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Chang, Yu-Wei; Ko, Tzu-Ping; Lee, Chien-Der; Chang, Yuan-Chih; Lin, Kuei-Ann; Chang, Chia-Seng; Wang, Andrew H.-J.; Wang, Ting-Fang
2009-01-01
RecA family proteins, including bacterial RecA, archaeal RadA, and eukaryotic Dmc1 and Rad51, mediate homologous recombination, a reaction essential for maintaining genome integrity. In the presence of ATP, these proteins bind a single-strand DNA to form a right-handed nucleoprotein filament, which catalyzes pairing and strand exchange with a homologous double-stranded DNA (dsDNA), by as-yet unknown mechanisms. We recently reported a structure of RadA left-handed helical filament, and here present three new structures of RadA left-handed helical filaments. Comparative structural analysis between different RadA/Rad51 helical filaments reveals that the N-terminal domain (NTD) of RadA/Rad51, implicated in dsDNA binding, is highly flexible. We identify a hinge region between NTD and polymerization motif as responsible for rigid body movement of NTD. Mutant analysis further confirms that structural flexibility of NTD is essential for RadA's recombinase activity. These results support our previous hypothesis that ATP-dependent axial rotation of RadA nucleoprotein helical filament promotes homologous recombination. PMID:19295907
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Functional formation of domain V of the poliovirus noncoding region: significance of unpaired bases.
Rowe, A; Burlison, J; Macadam, A J; Minor, P D
2001-10-10
Previously we have shown that polioviruses with mutations that disrupt the predicted secondary structure of the 5' noncoding region of domain V are temperature sensitive for growth. Non-temperature-sensitive revertant viruses had mutations that re-formed secondary structure by a direct back mutation of changes in the opposite strand. We mutated unpaired regions and selected revertants of viruses with single base deletions, where no obvious back mutation was available in order to gain information on secondary structure. Results indicated that conservation of length of a three base loop between two double-stranded stems was essential for a functional domain V to form. The requirement for the unpaired "hinge" base at 484 which is implicated in the attenuation of Sabin 2 was also confirmed. Results also underline the necessity for functional folding over local secondary structure stability. Copyright 2001 Academic Press.
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An Island Grouping Genetic Algorithm for Fuzzy Partitioning Problems
Salcedo-Sanz, S.; Del Ser, J.; Geem, Z. W.
2014-01-01
This paper presents a novel fuzzy clustering technique based on grouping genetic algorithms (GGAs), which are a class of evolutionary algorithms especially modified to tackle grouping problems. Our approach hinges on a GGA devised for fuzzy clustering by means of a novel encoding of individuals (containing elements and clusters sections), a new fitness function (a superior modification of the Davies Bouldin index), specially tailored crossover and mutation operators, and the use of a scheme based on a local search and a parallelization process, inspired from an island-based model of evolution. The overall performance of our approach has been assessed over a number of synthetic and real fuzzy clustering problems with different objective functions and distance measures, from which it is concluded that the proposed approach shows excellent performance in all cases. PMID:24977235
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A result on quasi-periodic solutions of a nonlinear beam equation with a quasi-periodic forcing term
NASA Astrophysics Data System (ADS)
Wang, Yi; Si, Jianguo
2012-02-01
In this paper, a quasi-periodically forced nonlinear beam equation {u_{tt}+u_{xxxx}+μ u+\\varepsilonφ(t)h(u)=0} with hinged boundary conditions is considered, where μ > 0, {\\varepsilon} is a small positive parameter, {φ} is a real analytic quasi-periodic function in t with a frequency vector ω = ( ω 1, ω 2 . . . , ω m ), and the nonlinearity h is a real analytic odd function of the form {h(u)=η_1u+η_{2bar{r}+1}u^{2bar{r}+1}+sum_{k≥ bar{r}+1}η_{2k+1}u^{2k+1},η_1,η_{2bar{r}+1} neq0, bar{r} in {mathbb {N}}.} The above equation admits a quasi-periodic solution.
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Swadźba, Elwira; Rupik, Weronika
2012-01-01
The monoclonal anti-cytokeratin 1/10 (LH1) antibody recognizing K1/K10 keratin epitopes that characterizes a keratinized epidermis of mammals cross-reacts with the beta and Oberhäutchen layers covering the scales and gastrosteges of grass snake embryos during the final period of epidermis differentiation. The immunolocalization of the anti-cytokeratin 1/10 (LH1) antibody appears in the beta layer of the epidermis, covering the outer surface of the gastrosteges at the beginning of developmental stage XI, and in the beta layer of the epidermis, covering the outer surface of the scales at the end of developmental stage XI. This antibody cross-reacts with the Oberhäutchen layers in the epidermis covering the outer surface of both scales and gastrosteges at developmental stages XI and XII just before its fusion with the beta layers. After fusion of the Oberhäutchen and beta layers, LH1 immunolabeling is weaker than before. This might suggest that alpha-keratins in these layers of the epidermis are masked by beta-keratins, modified, or degraded. The anti-cytokeratin 1/10 (LH1) antibody stains the Oberhäutchen layer in the epidermis covering the inner surface of the gastrosteges and the hinge regions between gastrosteges at the end of developmental stage XI. However, the Oberhäutchen of the epidermis covering the inner surfaces of the scales and the hinge regions between scales does not show cytokeratin 1/10 (LH1) immunolabeling until hatching. This cross-reactivity suggests that the beta and Oberhäutchen layers probably contain some alpha-keratins that react with the LH1 antibody. It is possible that these alpha-keratins create specific scaffolding for the latest beta-keratin deposition. It is also possible that the LH1 antibody cross-reacts with other epidermal proteins such as filament-associated proteins, i.e., filaggrin-like. The anti-cytokeratin 1/10 (LH1) antibody does not stain the alpha and mesos layers until hatching. We suppose that the differentiation of these layers will begin just after the first postnatal sloughing.
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Golay, Josée; Choblet, Sylvie; Iwaszkiewicz, Justyna; Cérutti, Pierre; Ozil, Annick; Loisel, Séverine; Pugnière, Martine; Ubiali, Greta; Zoete, Vincent; Michielin, Olivier; Berthou, Christian; Kadouche, Jean; Mach, Jean-Pierre; Duonor-Cérutti, Martine
2016-04-01
We have designed and validated a novel generic platform for production of tetravalent IgG1-like chimeric bispecific Abs. The VH-CH1-hinge domains of mAb2 are fused through a peptidic linker to the N terminus of mAb1 H chain, and paired mutations at the CH1-CL interface mAb1 are introduced that force the correct pairing of the two different free L chains. Two different sets of these CH1-CL interface mutations, called CR3 and MUT4, were designed and tested, and prototypic bispecific Abs directed against CD5 and HLA-DR were produced (CD5xDR). Two different hinge sequences between mAb1 and mAb2 were also tested in the CD5xDR-CR3 or -MUT4 background, leading to bispecific Ab (BsAbs) with a more rigid or flexible structure. All four Abs produced bound with good specificity and affinity to CD5 and HLA-DR present either on the same target or on different cells. Indeed, the BsAbs were able to efficiently redirect killing of HLA-DR(+) leukemic cells by human CD5(+) cytokine-induced killer T cells. Finally, all BsAbs had a functional Fc, as shown by their capacity to activate human complement and NK cells and to mediate phagocytosis. CD5xDR-CR3 was chosen as the best format because it had overall the highest functional activity and was very stable in vitro in both neutral buffer and in serum. In vivo, CD5xDR-CR3 was shown to have significant therapeutic activity in a xenograft model of human leukemia. Copyright © 2016 by The American Association of Immunologists, Inc.
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Yu, Xiu-chun; Xu, Ming; Song, Ruo-xian; Fu, Zhi-hou; Liu, Xiao-ping
2010-08-01
To study the long-term outcomes and complications of giant cell tumors around the knee treated with en bloc resection and reconstruction with prosthesis. From January 1991 to March 2005, 19 patients (11 men, 8 women, average age 35.4 years) were treated in our hospital with en bloc resection and reconstruction with domestic prosthesis (15 hinge knee and 4 rotating-hinge knee). The distal femur was involved in 12 and the proximal tibia in 7 cases. Nine tumors were primary and 10 recurrent. All cases were Campanacci grade III. The affected limb functions were evaluated by the Musculoskeletal Tumor Society scoring system. All patients underwent operation successfully with no complications. The mean follow-up time was 128.9 months (60 to 216 months). Apart from one patient who underwent amputation because of wound infection two years after reoperation, the range of knee motion of 18 patients was 30°-110°. The mean functional score of the affected limb was 22.7 (15 to 27 points). The length of the lower extremities was equal in nine cases; the affected limb was 2-9 cm shorter in the other ten cases. Prosthesis fracture and loosening developed in one, prosthesis aseptic loosening in three, and delayed deep infection and prosthesis loosening in two cases. The prosthesis loosening rate was 31.6%. One patient developed a proximal femur fracture. En bloc resection and reconstruction with prosthesis is a feasible method for treating giant cell tumor of bone around the knee. Complications related to the prosthesis, mainly prosthesis loosening and limb shortening, increase gradually with longer survival time. © 2010 Tianjin Hospital and Blackwell Publishing Asia Pty Ltd.
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Application of Balancing Tabs to Ailerons
NASA Technical Reports Server (NTRS)
Sears, Richard I.
1942-01-01
Analysis was made to determine characteristics required of a balancing-tab system for ailerons in order to reduce aileron stick forces to any desired magnitude. Series of calculations based on section data were made to determine balancing-tab systems of various chord tabs and ailerons that will give, for a particular airplane, zero rate of aileron hinge moment with aileron deflection and yet will produce same maximum rate of roll as a plain unbalanced 15-percent chord aileron of same span. Effects of rolling velocity and of forces in tab link on aileron hinge moments have been included.
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NASA Technical Reports Server (NTRS)
Macala, G. A.
1983-01-01
A computer program is described that can automatically generate symbolic equations of motion for systems of hinge-connected rigid bodies with tree topologies. The dynamical formulation underlying the program is outlined, and examples are given to show how a symbolic language is used to code the formulation. The program is applied to generate the equations of motion for a four-body model of the Galileo spacecraft. The resulting equations are shown to be a factor of three faster in execution time than conventional numerical subroutines.
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NASA Technical Reports Server (NTRS)
Fleischer, G. E.
1973-01-01
A new computer subroutine, which solves the attitude equations of motion for any vehicle idealized as a topological tree of hinge-connected rigid bodies, is used to simulate and analyze science instrument pointing control interaction with a flexible Mariner Venus/Mercury (MVM) spacecraft. The subroutine's user options include linearized or partially linearized hinge-connected models whose computational advantages are demonstrated for the MVM problem. Results of the pointing control/flexible vehicle interaction simulations, including imaging experiment pointing accuracy predictions and implications for MVM science sequence planning, are described in detail.
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Flow over a cylinder with a hinged-splitter plate
NASA Astrophysics Data System (ADS)
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 regime, the spectra of the oscillations become broadband, and are reminiscent of the change in character of the wake oscillations seen in the earlier fixed-rigid splitter plate case for L/D⩾5.0. In the present case of the hinged-splitter plate, the sudden transition seen as the splitter plate length (L/D) is increased from 3 to 4 may be attributed to the fact that the wake vortices are no longer able to synchronize with the plate motions for larger splitter plate lengths. Hence, as observed in other vortex-induced vibration problems, the oscillations become aperiodic and the amplitude reduces dramatically.
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Experimental and Analytical Seismic Studies of a Four-Span Bridge System with Innovative Materials
NASA Astrophysics Data System (ADS)
Cruz Noguez, Carlos Alonso
As part of a multi-university project utilizing the NSF Network for Earthquake Engineering Simulation (NEES), a quarter-scale model of a four-span bridge incorporating plastic hinges with different advanced materials was tested to failure on the three shake table system at the University of Nevada, Reno (UNR). The bridge was the second test model in a series of three 4-span bridges, with the first model being a conventional reinforced-concrete (RC) structure. The purpose of incorporating advanced materials was to improve the seismic performance of the bridge with respect to two damage indicators: (1) column damage and (2) permanent deformations. The goals of the study presented in this document were to (1) evaluate the seismic performance of a 4-span bridge system incorporating SMA/ECC and built-in rubber pad plastic hinges as well as post-tensioned piers, (2) quantify the relative merit of these advanced materials and details compared to each other and to conventional reinforced concrete plastic hinges, (3) determine the influence of abutment-superstructure interaction on the response, (4) examine the ability of available elaborate analytical modeling techniques to model the performance of advanced materials and details, and (5) conduct an extensive parametric study of different variations of the bridge model to study several important issues in bridge earthquake engineering. The bridge model included six columns, each pair of which utilized a different advanced detail at bottom plastic hinges: shape memory alloys (SMA), special engineered cementitious composites (ECC), elastomeric pads embedded into columns, and post-tensioning tendons. The design of the columns, location of the bents, and selection of the loading protocol were based on pre-test analyses conducted using computer program OpenSees. The bridge model was subjected to two-horizontal components of simulated earthquake records of the 1994 Northridge earthquake. Over 340 channels of data were collected. The test results showed the effectiveness of the advanced materials in reducing damage and permanent displacements. The damage was minimal in plastic hinges with SMA/ECC and those with built-in elastomeric pads. Conventional RC plastic hinges were severely damaged due to spalling of concrete and rupture of the longitudinal and transverse reinforcement. Extensive post-test analytical studies were conducted and it was determined that a computational model of the bridge that included bridge-abutment interaction using OpenSees was able to provide satisfactory estimations of key structural parameters such as superstructure displacements and base shears. The analytical model was also used to conduct parametric studies on single-column and bridge-system response under near-fault ground motions. The effects of vertical excitations and transverse shear-keys at the bridge abutments on the superstructure displacement and column drifts were also explored.
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Gadea, F; Favard, L; Boileau, P; Cuny, C; d'Ollone, T; Saragaglia, D; Sirveaux, F
2016-12-01
No objective criteria exist to help surgeons choose between IM nailing and plate fixation for 4-part fractures of the proximal humerus. The goal of this study was to identify radiological criteria that would make one technique a better choice than the other. This was a comparative, multicentre, retrospective study of 54 cases of antegrade nailing and 53 cases of plating performed between 1st January 2009 and 31 December 2011 for 4-part fractures of the proximal humerus. All patients had a minimum radiological and clinical follow-up of 18 months. The functional outcomes were evaluated using the weighted Constant score; a poor result was defined as a weighted Constant score<70%. The following radiological criteria were evaluated during the preoperative assessment and at the last follow-up: initial displacement and reduction of humeral head and tuberosities; morphology of the medial column (i.e. calcar comminution, posteromedial hinge, size of metaphyseal head extension); occurrence of avascular necrosis (AVN). After an average follow-up of 42 months, the weighted Constant scores and rate of poor outcomes were 77% and 48% in the nail group and 81% and 38% in the plate group, respectively (ns). The humeral head was reduced into an anatomical position, valgus or varus in 57%, 30% and 13% of cases in the nail group, and 58%, 29% and 13% in the plate group, respectively. The tuberosities healed in an anatomical position in 72% of nail cases and 70% of plate cases (ns). Only the presence of a medial hinge preoperatively had an effect on the functional outcomes in the nail and plate groups: the weighted Constant scores (P=0.05) and rate of poor outcomes (P=0.02) were 82% and 52% in the nail group and 97% and 9% in the plate group, respectively. The complication rates were comparable: the rates of AVN and articular screw penetration were 17% and 11% in the nail group, and 15% and 11% in the plate group, respectively. The surgical revision rate was 18.5% in the nail group and 30% in the plate group. If the medial hinge is preserved, we recommend locking plate fixation. In other cases, either technique can be used as long as the general rules of internal fixation are applied: reduction of the tuberosities, varus correction and stabilization of the calcar area. IV, retrospective study. Copyright © 2016 Elsevier Masson SAS. All rights reserved.
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A small molecule fusion inhibitor of dengue virus.
Poh, Mee Kian; Yip, Andy; Zhang, Summer; Priestle, John P; Ma, Ngai Ling; Smit, Jolanda M; Wilschut, Jan; Shi, Pei-Yong; Wenk, Markus R; Schul, Wouter
2009-12-01
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 (betaOG). Compounds blocking the betaOG pocket are thought to interfere with conformational changes in the envelope protein that are essential for fusion. Two fusion assays were developed to examine the anti-fusion activities of compounds. The first assay measures the cellular internalization of propidium iodide upon membrane fusion. The second assay measures the protease activity of trypsin upon fusion between dengue virions and trypsin-containing liposomes. We performed an in silico virtual screening for small molecules that can potentially bind to the betaOG pocket and tested these candidate molecules in the two fusion assays. We identified one compound that inhibits dengue fusion in both assays with an IC(50) of 6.8 microM and reduces viral titers with an EC(50) of 9.8 microM. Time-of-addition experiments showed that the compound was only active when present during viral infection but not when added 1h later, in agreement with a mechanism of action through fusion inhibition.
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Fracture mechanics modeling of popping event during daughter cell separation.
Jiang, Yuxuan; Liang, Xudong; Guo, Ming; Cao, Yanping; Cai, Shengqiang
2018-05-10
Most bacteria cells divide by binary fission which is part of a bacteria cell cycle and requires tight regulations and precise coordination. Fast separation of Staphylococcus Aureus (S. Aureus) daughter cells, named as popping event, has been observed in recent experiments. The popping event was proposed to be driven by mechanical crack propagation in the peripheral ring which connected two daughter cells before their separation. It has also been shown that after the fast separation, a small portion of the peripheral ring was left as a hinge. In the article, we develop a fracture mechanics model for the crack growth in the peripheral ring during S. Aureus daughter cell separation. In particular, using finite element analysis, we calculate the energy release rate associated with the crack growth in the peripheral ring, when daughter cells are inflated by a uniform turgor pressure inside. Our results show that with a fixed inflation of daughter cells, the energy release rate depends on the crack length non-monotonically. The energy release rate reaches a maximum value for a crack of an intermediate length. The non-monotonic relationship between the energy release rate and crack length clearly indicates that the crack propagation in the peripheral ring can be unstable. The computed energy release rate as a function of crack length can also be used to explain the existence of a small portion of peripheral ring remained as hinge after the popping event.
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Tang, Zhenhua; Gao, Ziwei; Jia, Shuhai; Wang, Fei; Wang, Yonglin
2017-05-01
3D structure assembly in advanced functional materials is important for many areas of technology. Here, a new strategy exploits IR light-driven bilayer polymeric composites for autonomic origami assembly of 3D structures. The bilayer sheet comprises a passive layer of poly(dimethylsiloxane) (PDMS) and an active layer comprising reduced graphene oxides (RGOs), thermally expanding microspheres (TEMs), and PDMS. The corresponding fabrication method is versatile and simple. Owing to the large volume expansion of the TEMs, the two layers exhibit large differences in their coefficients of thermal expansion. The RGO-TEM-PDMS/PDMS bilayers can deflect toward the PDMS side upon IR irradiation via the cooperative effect of the photothermal effect of the RGOs and the expansion of the TEMs, and exhibit excellent light-driven, a large bending deformation, and rapid responsive properties. The proposed RGO-TEM-PDMS/PDMS composites with excellent light-driven bending properties are demonstrated as active hinges for building 3D geometries such as bidirectionally folded columns, boxes, pyramids, and cars. The folding angle (ranging from 0° to 180°) is well-controlled by tuning the active hinge length. Furthermore, the folded 3D architectures can permanently preserve the deformed shape without energy supply. The presented approach has potential in biomedical devices, aerospace applications, microfluidic devices, and 4D printing.
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Zhao, Yaofeng; Cui, Huiting; Whittington, Camilla M; Wei, Zhiguo; Zhang, Xiaofeng; Zhang, Ziding; Yu, Li; Ren, Liming; Hu, Xiaoxiang; Zhang, Yaping; Hellman, Lars; Belov, Katherine; Li, Ning; Hammarström, Lennart
2009-09-01
The evolutionary origins of mammalian immunoglobulin H chain isotypes (IgM, IgD, IgG, IgE, and IgA) are still incompletely understood as these isotypes differ considerably in structure and number from their counterparts in nonmammalian tetrapods. We report in this study that the platypus (Ornithorhynchus anatinus) Ig H chain constant region gene locus contains eight Ig encoding genes, which are arranged in an mu-delta-omicron-gamma2-gamma1-alpha1-epsilon-alpha2 order, spanning a total of approximately 200 kb DNA, encoding six distinct isotypes. The omicron (omicron for Ornithorhynchus) gene encodes a novel Ig H chain isotype that consists of four constant region domains and a hinge, and is structurally different from any of the five known mammalian Ig classes. This gene is phylogenetically related to upsilon (epsilon) and gamma, and thus appears to be a structural intermediate between these two genes. The platypus delta gene encodes ten heavy chain constant region domains, lacks a hinge region and is similar to IgD in amphibians and fish, but strikingly different from that in eutherian mammals. The platypus Ig H chain isotype repertoire thus shows a unique combination of genes that share similarity both to those of nonmammalian tetrapods and eutherian animals and demonstrates how phylogenetically informative species can be used to reconstruct the evolutionary history of functionally important genes.
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Skip residues modulate the structural properties of the myosin rod and guide thick filament assembly
Taylor, Keenan C.; Buvoli, Massimo; Korkmaz, Elif Nihal; ...
2015-07-06
The rod of sarcomeric myosins directs thick filament assembly and is characterized by the insertion of four skip residues that introduce discontinuities in the coiled-coil heptad repeats. We report in this paper that the regions surrounding the first three skip residues share high structural similarity despite their low sequence homology. Near each of these skip residues, the coiled-coil transitions to a nonclose-packed structure inducing local relaxation of the superhelical pitch. Moreover, molecular dynamics suggest that these distorted regions can assume different conformationally stable states. In contrast, the last skip residue region constitutes a true molecular hinge, providing C-terminal rod flexibility.more » Assembly of myosin with mutated skip residues in cardiomyocytes shows that the functional importance of each skip residue is associated with rod position and reveals the unique role of the molecular hinge in promoting myosin antiparallel packing. By defining the biophysical properties of the rod, the structures and molecular dynamic calculations presented here provide insight into thick filament formation, and highlight the structural differences occurring between the coiled-coils of myosin and the stereotypical tropomyosin. Finally, in addition to extending our knowledge into the conformational and biological properties of coiled-coil discontinuities, the molecular characterization of the four myosin skip residues also provides a guide to modeling the effects of rod mutations causing cardiac and skeletal myopathies.« less
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Nivarthi, Usha K.; Kose, Nurgun; Sapparapu, Gopal; Widman, Douglas; Gallichotte, Emily; Pfaff, Jennifer M.; Doranz, Benjamin J.; Weiskopf, Daniela; Sette, Alessandro; Durbin, Anna P.; Whitehead, Steve S.; Baric, Ralph
2016-01-01
ABSTRACT The four dengue virus (DENV) serotypes are mosquito-borne flaviviruses responsible for dengue fever and dengue hemorrhagic fever. People exposed to DENV develop antibodies (Abs) that strongly neutralize the serotype responsible for infection. Historically, infection with DENV serotype 4 (DENV4) has been less common and less studied than infections with the other three serotypes. However, DENV4 has been responsible for recent large and sustained epidemics in Asia and Latin America. The neutralizing antibody responses and the epitopes targeted against DENV4 have not been characterized in human infection. In this study, we mapped and characterized epitopes on DENV4 recognized by neutralizing antibodies in people previously exposed to DENV4 infections or to a live attenuated DENV4 vaccine. To study the fine specificity of DENV4 neutralizing human antibodies, B cells from two people exposed to DENV4 were immortalized and screened to identify DENV-specific clones. Two human monoclonal antibodies (MAbs) that neutralized DENV4 were isolated, and their epitopes were finely mapped using recombinant viruses and alanine scan mutation array techniques. Both antibodies bound to quaternary structure epitopes near the hinge region between envelope protein domain I (EDI) and EDII. In parallel, to characterize the serum neutralizing antibody responses, convalescence-phase serum samples from people previously exposed to primary DENV4 natural infections or a monovalent DENV4 vaccine were analyzed. Natural infection and vaccination also induced serum-neutralizing antibodies that targeted similar epitope domains at the EDI/II hinge region. These studies defined a target of neutralizing antigenic site on DENV4 targeted by human antibodies following natural infection or vaccination. IMPORTANCE The four serotypes of dengue virus are the causative agents of dengue fever and dengue hemorrhagic fever. People exposed to primary DENV infections develop long-term neutralizing antibody responses, but these principally recognize only the infecting serotype. An effective vaccine against dengue should elicit long-lasting protective antibody responses to all four serotypes simultaneously. We and others have defined antigenic sites on the envelope (E) protein of viruses of dengue virus serotypes 1, 2, and 3 targeted by human neutralizing antibodies. The epitopes on DENV4 E protein targeted by the human neutralizing antibodies and the mechanisms of serotype 4 neutralization are poorly understood. Here, we report the properties of human antibodies that neutralize dengue virus serotype 4. People exposed to serotype 4 infections or a live attenuated serotype 4 vaccine developed neutralizing antibodies that bound to similar sites on the viral E protein. These studies have provided a foundation for developing and evaluating DENV4 vaccines. PMID:28031369