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Sample records for actin-binding domain abd

  1. Hypertrophic cardiomyopathy mutations in the calponin-homology domain of ACTN2 affect actin binding and cardiomyocyte Z-disc incorporation

    PubMed Central

    Haywood, Natalie J.; Wolny, Marcin; Rogers, Brendan; Trinh, Chi H.; Shuping, Yu; Edwards, Thomas A.; Peckham, Michelle

    2016-01-01

    α-Actinin-2 (ACTN2) is the only muscle isoform of α-actinin expressed in cardiac muscle. Mutations in this protein have been implicated in mild to moderate forms of hypertrophic cardiomyopathy (HCM). We have investigated the effects of two mutations identified from HCM patients, A119T and G111V, on the secondary and tertiary structure of a purified actin binding domain (ABD) of ACTN2 by circular dichroism and X-ray crystallography, and show small but distinct changes for both mutations. We also find that both mutants have reduced F-actin binding affinity, although the differences are not significant. The full length mEos2 tagged protein expressed in adult cardiomyocytes shows that both mutations additionally affect Z-disc localization and dynamic behaviour. Overall, these two mutations have small effects on structure, function and behaviour, which may contribute to a mild phenotype for this disease. PMID:27287556

  2. The N-terminal actin-binding tandem calponin-homology (CH) domain of dystrophin is in a closed conformation in solution and when bound to F-actin.

    PubMed

    Singh, Surinder M; Mallela, Krishna M G

    2012-11-01

    Deficiency of the vital muscle protein dystrophin triggers Duchenne/Becker muscular dystrophy, but the structure-function relationship of dystrophin is poorly understood. To date, molecular structures of three dystrophin domains have been determined, of which the N-terminal actin-binding domain (N-ABD or ABD1) is of particular interest. This domain is composed of two calponin-homology (CH) domains, which form an important class of ABDs in muscle proteins. A previously determined x-ray structure indicates that the dystrophin N-ABD is a domain-swapped dimer, with each monomer adopting an extended, open conformation in which the two CH domains do not interact. This structure is controversial because it contradicts functional studies and known structures of similar ABDs from other muscle proteins. Here, we investigated the solution conformation of the dystrophin N-ABD using a very simple and elegant technique of pyrene excimer fluorescence. Using the wild-type protein, which contains two cysteines, and the corresponding single-cysteine mutants, we show that the protein is a monomer in solution and is in a closed conformation in which the two CH domains seem to interact, as observed from the excimer fluorescence of pyrene-labeled wild-type protein. Excimer fluorescence was also observed in its actin-bound form, indicating that the dystrophin N-ABD binds to F-actin in a closed conformation. Comparison of the dystrophin N-ABD conformation with other ABDs indicates that the tandem CH domains in general may be monomeric in solution and predominantly occur in closed conformation, whereas their actin-bound conformations may differ.

  3. Comparative genome analysis of cortactin and HS1: the significance of the F-actin binding repeat domain

    PubMed Central

    van Rossum, Agnes GSH; Schuuring-Scholtes, Ellen; Seggelen, Vera van Buuren-van; Kluin, Philip M; Schuuring, Ed

    2005-01-01

    Background In human carcinomas, overexpression of cortactin correlates with poor prognosis. Cortactin is an F-actin-binding protein involved in cytoskeletal rearrangements and cell migration by promoting actin-related protein (Arp)2/3 mediated actin polymerization. It shares a high amino acid sequence and structural similarity to hematopoietic lineage cell-specific protein 1 (HS1) although their functions differ considerable. In this manuscript we describe the genomic organization of these two genes in a variety of species by a combination of cloning and database searches. Based on our analysis, we predict the genesis of the actin-binding repeat domain during evolution. Results Cortactin homologues exist in sponges, worms, shrimps, insects, urochordates, fishes, amphibians, birds and mammalians, whereas HS1 exists in vertebrates only, suggesting that both genes have been derived from an ancestor cortactin gene by duplication. In agreement with this, comparative genome analysis revealed very similar exon-intron structures and sequence homologies, especially over the regions that encode the characteristic highly conserved F-actin-binding repeat domain. Cortactin splice variants affecting this F-actin-binding domain were identified not only in mammalians, but also in amphibians, fishes and birds. In mammalians, cortactin is ubiquitously expressed except in hematopoietic cells, whereas HS1 is mainly expressed in hematopoietic cells. In accordance with their distinct tissue specificity, the putative promoter region of cortactin is different from HS1. Conclusions Comparative analysis of the genomic organization and amino acid sequences of cortactin and HS1 provides inside into their origin and evolution. Our analysis shows that both genes originated from a gene duplication event and subsequently HS1 lost two repeats, whereas cortactin gained one repeat. Our analysis genetically underscores the significance of the F-actin binding domain in cytoskeletal remodeling, which

  4. Structural and Functional Dissection of the Abp1 ADFH Actin-binding Domain Reveals Versatile In Vivo Adapter Functions

    SciTech Connect

    Quintero-Monzon,O.; Rodal, A.; Strokopytov, B.; Almo, S.; Goode, B.

    2005-01-01

    Abp1 is a multidomain protein that regulates the Arp2/3 complex and links proteins involved in endocytosis to the actin cytoskeleton. All of the proposed cellular functions of Abp1 involve actin filament binding, yet the actin binding site(s) on Abp1 have not been identified, nor has the importance of actin binding for Abp1 localization and function in vivo been tested. Here, we report the crystal structure of the Saccharomyces cerevisiae Abp1 actin-binding actin depolymerizing factor homology (ADFH) domain and dissect its activities by mutagenesis. Abp1-ADFH domain and ADF/cofilin structures are similar, and they use conserved surfaces to bind actin; however, there are also key differences that help explain their differential effects on actin dynamics. Using point mutations, we demonstrate that actin binding is required for localization of Abp1 in vivo, the lethality caused by Abp1 overexpression, and the ability of Abp1 to activate Arp2/3 complex. Furthermore, we genetically uncouple ABP1 functions that overlap with SAC6, SLA1, and SLA2, showing they require distinct combinations of activities and interactions. Together, our data provide the first structural and functional view of the Abp1-actin interaction and show that Abp1 has distinct cellular roles as an adapter, linking different sets of ligands for each function.

  5. Multiple actin binding domains of Ena/VASP proteins determine actin network stiffening.

    PubMed

    Gentry, Brian S; van der Meulen, Stef; Noguera, Philippe; Alonso-Latorre, Baldomero; Plastino, Julie; Koenderink, Gijsje H

    2012-11-01

    Vasodilator-stimulated phosphoprotein (Ena/VASP) is an actin binding protein, important for actin dynamics in motile cells and developing organisms. Though VASP's main activity is the promotion of barbed end growth, it has an F-actin binding site and can form tetramers, and so could additionally play a role in actin crosslinking and bundling in the cell. To test this activity, we performed rheology of reconstituted actin networks in the presence of wild-type VASP or mutants lacking the ability to tetramerize or to bind G-actin and/or F-actin. We show that increasing amounts of wild-type VASP increase network stiffness up to a certain point, beyond which stiffness actually decreases with increasing VASP concentration. The maximum stiffness is 10-fold higher than for pure actin networks. Confocal microscopy shows that VASP forms clustered actin filament bundles, explaining the reduction in network elasticity at high VASP concentration. Removal of the tetramerization site results in significantly reduced bundling and bundle clustering, indicating that VASP's flexible tetrameric structure causes clustering. Removing either the F-actin or the G-actin binding site diminishes VASP's effect on elasticity, but does not eliminate it. Mutating the F-actin and G-actin binding site together, or mutating the F-actin binding site and saturating the G-actin binding site with monomeric actin, eliminates VASP's ability to increase network stiffness. We propose that, in the cell, VASP crosslinking confers only moderate increases in linear network elasticity, and unlike other crosslinkers, VASP's network stiffening activity may be tuned by the local concentration of monomeric actin.

  6. A human β-III-spectrin spinocerebellar ataxia type 5 mutation causes high-affinity F-actin binding

    PubMed Central

    Avery, Adam W.; Crain, Jonathan; Thomas, David D.; Hays, Thomas S.

    2016-01-01

    Spinocerebellar ataxia type 5 (SCA5) is a human neurodegenerative disease that stems from mutations in the SPTBN2 gene encoding the protein β-III-spectrin. Here we investigated the molecular consequence of a SCA5 missense mutation that results in a L253P substitution in the actin-binding domain (ABD) of β-III-spectrin. We report that the L253P substitution in the isolated β-III-spectrin ABD causes strikingly high F-actin binding affinity (Kd = 75.5 nM) compared to the weak F-actin binding affinity of the wild-type ABD (Kd = 75.8 μM). The mutation also causes decreased thermal stability (Tm = 44.6 °C vs 59.5 °C). Structural analyses indicate that leucine 253 is in a loop at the interface of the tandem calponin homology (CH) domains comprising the ABD. Leucine 253 is predicted to form hydrophobic contacts that bridge the CH domains. The decreased stability of the mutant indicates that these bridging interactions are probably disrupted, suggesting that the high F-actin binding affinity of the mutant is due to opening of the CH domain interface. These results support a fundamental role for leucine 253 in regulating opening of the CH domain interface and binding of the ABD to F-actin. This study indicates that high-affinity actin binding of L253P β-III-spectrin is a likely driver of neurodegeneration. PMID:26883385

  7. Inhibition of tobacco mosaic virus movement by expression of an actin-binding protein.

    PubMed

    Hofmann, Christina; Niehl, Annette; Sambade, Adrian; Steinmetz, André; Heinlein, Manfred

    2009-04-01

    The tobacco mosaic virus (TMV) movement protein (MP) required for the cell-to-cell spread of viral RNA interacts with the endoplasmic reticulum (ER) as well as with the cytoskeleton during infection. Whereas associations of MP with ER and microtubules have been intensely investigated, research on the role of actin has been rather scarce. We demonstrate that Nicotiana benthamiana plants transgenic for the actin-binding domain 2 of Arabidopsis (Arabidopsis thaliana) fimbrin (AtFIM1) fused to green fluorescent protein (ABD2:GFP) exhibit a dynamic ABD2:GFP-labeled actin cytoskeleton and myosin-dependent Golgi trafficking. These plants also support the movement of TMV. In contrast, both myosin-dependent Golgi trafficking and TMV movement are dominantly inhibited when ABD2:GFP is expressed transiently. Inhibition is mediated through binding of ABD2:GFP to actin filaments, since TMV movement is restored upon disruption of the ABD2:GFP-labeled actin network with latrunculin B. Latrunculin B shows no significant effect on the spread of TMV infection in either wild-type plants or ABD2:GFP transgenic plants under our treatment conditions. We did not observe any binding of MP along the length of actin filaments. Collectively, these observations demonstrate that TMV movement does not require an intact actomyosin system. Nevertheless, actin-binding proteins appear to have the potential to exert control over TMV movement through the inhibition of myosin-associated protein trafficking along the ER membrane.

  8. Molecular analysis of insertion/deletion mutations in protein 4.1 in elliptocytosis. I. Biochemical identification of rearrangements in the spectrin/actin binding domain and functional characterizations.

    PubMed Central

    Marchesi, S L; Conboy, J; Agre, P; Letsinger, J T; Marchesi, V T; Speicher, D W; Mohandas, N

    1990-01-01

    Protein 4.1 (80 kD) interacts with spectrin and short actin filaments to form the erythrocyte membrane skeleton. Mutations of spectrin and protein 4.1 are associated with elliptocytosis or spherocytosis and anemia of varying severity. We analyzed two mutant protein 4.1 molecules associated with elliptocytosis: a high molecular weight 4.1 (95 kD) associated with mild elliptocytosis without anemia, and a low molecular weight 4.1 (two species at 68 and 65 kD) associated with moderate elliptocytosis and anemia. 4.1(95) was found to contain a approximately 15-kD insertion adjacent to the spectrin/actin binding domain comprised, at least in part, of repeated sequence. 4.1(68/65) was found to lack the entire spectrin-actin binding domain. The mechanical stability of erythrocyte membranes containing 4.1(95) was identical to that of normal membranes, consistent with the presence of an intact spectrin-actin binding domain in protein 4.1. In contrast, membranes containing 4.1(68/65) have markedly reduced mechanical stability as a result of deleting the spectrin-actin binding domain. The mechanical stability of these membranes was improved following reconstitution with normal 4.1. These studies have thus enabled us to establish the importance of the spectrin-actin binding domain in regulating the mechanical stability of the erythrocyte membrane. Images PMID:2384597

  9. Ezrin self-association involves binding of an N-terminal domain to a normally masked C-terminal domain that includes the F-actin binding site.

    PubMed Central

    Gary, R; Bretscher, A

    1995-01-01

    Ezrin is a membrane-cytoskeletal linking protein that is concentrated in actin-rich surface structures. It is closely related to the microvillar proteins radixin and moesin and to the tumor suppressor merlin/schwannomin. Cell extracts contain ezrin dimers and ezrin-moesin heterodimers in addition to monomers. Truncated ezrin fusion proteins were assayed by blot overlay to determine which regions mediate self-association. Here we report that ezrin self-association occurs by head-to-tail joining of distinct N-terminal and C-terminal domains. It is likely that these domains, termed N- and C-ERMADs (ezrin-radixin-moesin association domain), are responsible for homotypic and heterotypic associations among ERM family members. The N-ERMAD of ezrin resided within amino acids 1-296; deletion of 10 additional residues resulted in loss of activity. The C-ERMAD was mapped to the last 107 amino acids of ezrin, residues 479-585. The two residues at the C-terminus were required for activity, and the region from 530-585 was insufficient. The C-ERMAD was masked in the native monomer. Exposure of this domain required unfolding ezrin with sodium dodecyl sulfate or expressing the domain as part of a truncated protein. Intermolecular association could not occur unless the C-ERMAD had been made accessible to its N-terminal partner. It can be inferred that dimerization in vivo requires an activation step that exposes this masked domain. The conformationally inaccessible C-terminal region included the F-actin binding site, suggesting that this activity is likewise regulated by masking. Images PMID:7579708

  10. Mechanochemistry of protein 4.1's spectrin-actin-binding domain: ternary complex interactions, membrane binding, network integration, structural strengthening

    PubMed Central

    1995-01-01

    Mechanical strength of the red cell membrane is dependent on ternary interactions among the skeletal proteins, spectrin, actin, and protein 4.1. Protein 4.1's spectrin-actin-binding (SAB) domain is specified by an alternatively spliced exon encoding 21 amino acid (aa) and a constitutive exon encoding 59 aa. A series of truncated SAB peptides were engineered to define the sequences involved in spectrin-actin interactions, and also membrane strength. Analysis of in vitro supramolecular assemblies showed that gelation activity of SAB peptides correlates with their ability to recruit a critical amount of spectrin into the complex to cross-link actin filaments. Also, several SAB peptides appeared to exhibit a weak, cooperative actin-binding activity which mapped to the first 26 residues of the constitutive 59 aa. Fluorescence-imaged microdeformation was used to show SAB peptide integration into the elastic skeletal network of spectrin, actin, and protein 4.1. In situ membrane-binding and membrane-strengthening abilities of the SAB peptides correlated with their in vitro gelation activity. The findings imply that sites for strong spectrin binding include both the alternative 21-aa cassette and a conserved region near the middle of the 59 aa. However, it is shown that only weak SAB affinity is necessary for physiologically relevant action. Alternatively spliced exons can thus translate into strong modulation of specific protein interactions, economizing protein function in the cell without, in and of themselves, imparting unique function. PMID:7642705

  11. Two domains of the epidermal growth factor receptor are involved in cytoskeletal interactions

    SciTech Connect

    Song Wei; Wu Jing; Ge Gaoxiang; Lin Qishui

    2008-06-13

    Epidermal growth factor receptor can interact directly with F-actin through an actin-binding domain. In the present study, a mutant EGFR, lacking a previously identified actin-binding domain (ABD 1), was still able to bind elements of the cytoskeleton. A second EGFR actin-binding domain (ABD 2) was identified in the region of the receptor that includes Tyr-1148 by a yeast two-hybrid assay. GST fusion proteins comprising ABD 1 or ABD 2 bound actin in vitro and competed for actin-binding with the full-length EGFR. EGFR binding to actin was also studied in intact cells using fluorescence resonance energy transfer (FRET). The localization of the EGFR/actin-binding complex changed after EGF stimulation. Fusion proteins containing mutations in ABD1 or ABD2 did not display a FRET signal. The results lead to the conclusion that the interaction between ABD1 and ABD2 and actin during EGF-induced signal transduction, and thus between EGFR and actin, are important in cell activation.

  12. The EGF receptor is an actin-binding protein

    PubMed Central

    1992-01-01

    In a number of recent studies it has been shown that in vivo part of the EGF receptor (EGFR) population is associated to the actin filament system. In this paper we demonstrate that the purified EGFR can be cosedimented with purified filamentous actin (F-actin) indicating a direct association between EGFR and actin. A truncated EGFR, previously shown not to be associated to the cytoskeleton, was used as a control and this receptor did not cosediment with actin filaments. Determination of the actin-binding domain of the EGFR was done by measuring competition of either a polyclonal antibody or synthetic peptides on EGFR cosedimentation with F-actin. A synthetic peptide was made homologous to amino acid residues 984-996 (HL-33) of the EGFR which shows high homology with the actin-binding domain of Acanthamoeba profilin. A polyclonal antibody raised against HL-33 was found to prevent cosedimentation of EGFR with F-actin. This peptide HL-33 was shown to bind directly to actin in contrast with a synthetic peptide homologous to residues 1001-1013 (HL-34). During cosedimentation, HL-33 competed for actin binding of the EGFR and HL-34 did not, indicating that the EGFR contains one actin-binding site. These results demonstrate that the EGFR is an actin-binding protein which binds to actin via a domain containing amino acids residues 984-996. PMID:1383230

  13. Mutation analysis of the short cytoplasmic domain of the cell-cell adhesion molecule CEACAM1 identifies residues that orchestrate actin binding and lumen formation.

    PubMed

    Chen, Charng-Jui; Kirshner, Julia; Sherman, Mark A; Hu, Weidong; Nguyen, Tung; Shively, John E

    2007-02-23

    CEACAM1-4S (carcinoembryonic antigen cell adhesion molecule 1, with 4 ectodomains and a short, 12-14 amino acid cytoplasmic domain) mediates lumen formation via an apoptotic and cytoskeletal reorganization mechanism when mammary epithelial cells are grown in a three-dimensional model of mammary morphogenesis. We show by quantitative yeast two-hybrid, BIAcore, NMR HSQC and STD, and confocal analyses that amino acids phenylalanine (Phe(454)) and lysine (Lys(456)) are key residues that interact with actin orchestrating the cytoskeletal reorganization. A CEACAM1 membrane model based on vitamin D-binding protein that predicts an interaction of Phe(454) at subdomain 3 of actin was supported by inhibition of binding of actin to vitamin D-binding protein by the cytoplasmic domain peptide. We also show that residues Thr(457) and/or Ser(459) are phosphorylated in CEACAM1-transfected cells grown in three-dimensional culture and that mutation analysis of these residues (T457A/S459A) or F454A blocks lumen formation. These studies demonstrate that a short cytoplasmic domain membrane receptor can directly mediate substantial intracellular signaling.

  14. Transvection in the Drosophila Abd-B domain: extensive upstream sequences are involved in anchoring distant cis-regulatory regions to the promoter.

    PubMed Central

    Sipos, L; Mihály, J; Karch, F; Schedl, P; Gausz, J; Gyurkovics, H

    1998-01-01

    the iab regulatory domains to Abd-B. Possible implications of the tethering complex for the regulation of Abd-B are discussed. In addition, we present evidence that the tenacity of trans-interactions in the Abd-B gene may vary, depending upon the tissue and stage of development. PMID:9611211

  15. Filament Assembly by Spire: Key Residues and Concerted Actin Binding

    PubMed Central

    Rasson, Amy S.; Bois, Justin S.; Pham, Duy Stephen L.; Yoo, Haneul; Quinlan, Margot E.

    2014-01-01

    The most recently identified class of actin nucleators, WASp Homology domain 2 (WH2) – nucleators, use tandem repeats of monomeric actin-binding WH2 domains to facilitate actin nucleation. WH2 domains are involved in a wide variety of actin regulatory activities. Structurally, they are expected to clash with interprotomer contacts within the actin filament. Thus, the discovery of their role in nucleation was surprising. Here we use Drosophila Spire (Spir) as a model system to investigate both how tandem WH2 domains can nucleate actin and what differentiates nucleating WH2-containing proteins from their non-nucleating counterparts. We found that the third WH2 domain in Spir (Spir-C or Sc), plays a unique role. In the context of a short nucleation construct (containing only two WH2 domains), placement of Sc in the N-terminal position was required for the most potent nucleation. We found that the native organization of the WH2 domains with respect to each other is necessary for binding to actin with positive cooperativity. We identified two residues within Sc that are critical for its activity. Using this information we were able to convert a weak synthetic nucleator into one with activity equal to a native Spir construct. Lastly, we found evidence that Sc binds actin filaments, in addition to monomers. PMID:25234086

  16. Filament assembly by Spire: key residues and concerted actin binding.

    PubMed

    Rasson, Amy S; Bois, Justin S; Pham, Duy Stephen L; Yoo, Haneul; Quinlan, Margot E

    2015-02-27

    The most recently identified class of actin nucleators, WASp homology domain 2 (WH2) nucleators, use tandem repeats of monomeric actin-binding WH2 domains to facilitate actin nucleation. WH2 domains are involved in a wide variety of actin regulatory activities. Structurally, they are expected to clash with interprotomer contacts within the actin filament. Thus, the discovery of their role in nucleation was surprising. Here we use Drosophila Spire (Spir) as a model system to investigate both how tandem WH2 domains can nucleate actin and what differentiates nucleating WH2-containing proteins from their non-nucleating counterparts. We found that the third WH2 domain in Spir (Spir-C or SC) plays a unique role. In the context of a short nucleation construct (containing only two WH2 domains), placement of SC in the N-terminal position was required for the most potent nucleation. We found that the native organization of the WH2 domains with respect to each other is necessary for binding to actin with positive cooperativity. We identified two residues within SC that are critical for its activity. Using this information, we were able to convert a weak synthetic nucleator into one with activity equal to a native Spir construct. Lastly, we found evidence that SC binds actin filaments, in addition to monomers.

  17. Phosphorylation of platelet actin-binding protein during platelet activation

    SciTech Connect

    Carroll, R.C.; Gerrard, J.M.

    1982-03-01

    In this study we have followed the 32P-labeling of actin-binding protein as a function of platelet activation. Utilizing polyacrylamide-sodium dodecyl sulfate gel electrophoresis to resolve total platelet protein samples, we found 2 to 3-fold labeling increases in actin-binding protein 30 to 60 sec after thrombin stimulation. Somewhat larger increases were observed for 40,000 and 20,000 apparent molecular weight peptides. The actin-binding protein was identified on the gels by coelectrophoresis with purified actin-binding protein, its presence in cytoskeletal cores prepared by detergent extraction of activated 32P-labeled platelets, and by direct immunoprecipitation with antibodies against guinea pig vas deferens filamin (actin-binding protein). In addition, these cytoskeletal cores indicated that the 32P-labeled actin-binding protein was closely associated with the activated platelet's cytoskeleton. Following the 32P-labeling of actin-binding protein over an 8-min time course revealed that in aggregating platelet samples rapid dephosphorylation to almost initial levels occurred between 3 and 5 min. A similar curve was obtained for the 20,000 apparent molecular weight peptide. However, rapid dephosphorylation was not observed if platelet aggregation was prevented by chelating external calcium or by using thrombasthenic platelets lacking the aggregation response. Thus, cell-cell contact would seem to be crucial in initiating the rapid dephosphorylation response.

  18. Actin binding proteins, spermatid transport and spermiation.

    PubMed

    Qian, Xiaojing; Mruk, Dolores D; Cheng, Yan-Ho; Tang, Elizabeth I; Han, Daishu; Lee, Will M; Wong, Elissa W P; Cheng, C Yan

    2014-06-01

    The transport of germ cells across the seminiferous epithelium is composed of a series of cellular events during the epithelial cycle essential to the completion of spermatogenesis. Without the timely transport of spermatids during spermiogenesis, spermatozoa that are transformed from step 19 spermatids in the rat testis fail to reach the luminal edge of the apical compartment and enter the tubule lumen at spermiation, thereby arriving the epididymis for further maturation. Step 19 spermatids and/or sperms that remain in the epithelium beyond stage VIII of the epithelial cycle will be removed by the Sertoli cell via phagocytosis to form phagosomes and be degraded by lysosomes, leading to subfertility and/or infertility. However, the biology of spermatid transport, in particular the final events that lead to spermiation remain elusive. Based on recent data in the field, we critically evaluate the biology of spermiation herein by focusing on the actin binding proteins (ABPs) that regulate the organization of actin microfilaments at the Sertoli-spermatid interface, which is crucial for spermatid transport during this event. The hypothesis we put forth herein also highlights some specific areas of research that can be pursued by investigators in the years to come.

  19. Integration of the Rac1- and actin-binding properties of Coronin-1C

    PubMed Central

    Tilley, Frances C; Williamson, Rosalind C; Race, Paul R; Rendall, Thomas C; Bass, Mark D

    2015-01-01

    The coronin family of actin-binding proteins regulate actin branching by inhibiting Arp2/3. We recently reported 2 interactions that were unique to coronin-1C: binding of a Rac1 inhibitor, RCC2, to the unique linker region and Rac1 itself to the propeller domain in a manner that differs from that proposed for other coronins. Through these interactions coronin-1C redistributes Rac1 from the back of the cell to the leading edge for either activation or sequestration by the associated Rac1-inhibitor, RCC2. Here we investigate the relationship between the Rac1- and actin-binding properties of coronin-1C and find that, although actin appears to be involved in the retrafficking of Rac1, signaling by Rac1 lies upstream of the stress fiber-formation, for which the coronins were originally characterized. PMID:25862165

  20. Cloning and sequencing of a gene coding for an actin binding protein of Saccharomyces exiguus.

    PubMed

    Lange, U; Steiner, S; Grolig, F; Wagner, G; Philippsen, P

    1994-03-01

    The actin binding protein Abp1p of the yeast Saccharomyces cervisiae is thought to be involved in the spatial organisation of cell surface growth. It contains a potential actin binding domain and an SH-3 region, a common motif of many signal transduction proteins [1]. We have cloned and sequenced an ABP1 homologous gene of Saccharomyces exiguus, a yeast which is only distantly related to S. cerevisiae. The protein encoded by this gene is slightly larger than the respective S. cerevisiae protein (617 versus 592 amino acids). The two genes are 67.4% identical and the deduced amino acid sequences share an overall identity of 59.8%. The most conserved regions are the 148 N-terminal amino acids containing the potential actin binding site and the 58 C-terminal amino acids including the SH3 domain. In addition, both proteins contain a repeated motif of unknown function which is rich in glutamic acids with the sequence EEEEEEEAPAPSLPSR in the S. exiguus Abp1p. PMID:8110838

  1. Tissue Expression and Actin Binding of a Novel N-Terminal Utrophin Isoform

    PubMed Central

    Zuellig, Richard A.; Bornhauser, Beat C.; Amstutz, Ralf; Constantin, Bruno; Schaub, Marcus C.

    2011-01-01

    Utrophin and dystrophin present two large proteins that link the intracellular actin cytoskeleton to the extracellular matrix via the C-terminal-associated protein complex. Here we describe a novel short N-terminal isoform of utrophin and its protein product in various rat tissues (N-utro, 62 kDa, amino acids 1–539, comprising the actin-binding domain plus the first two spectrin repeats). Using different N-terminal recombinant utrophin fragments, we show that actin binding exhibits pronounced negative cooperativity (affinity constants K1 = ∼5 × 106 and K2 = ∼1 × 105 M−1) and is Ca2+-insensitive. Expression of the different fragments in COS7 cells and in myotubes indicates that the actin-binding domain alone binds exlusively to actin filaments. The recombinant N-utro analogue binds in vitro to actin and in the cells associates to the membranes. The results indicate that N-utro may be responsible for the anchoring of the cortical actin cytoskeleton to the membranes in muscle and other tissues. PMID:22228988

  2. High-Resolution Crystal Structures of Villin Headpiece nad Mutants with Reduced F-Actin Binding Activity

    SciTech Connect

    Meng,J.; Vardar, D.; Wang, Y.; Guo, H.; Head, J.; McKnight, C.

    2005-01-01

    Villin-type headpiece domains are approximately 70 amino acid modular motifs found at the C terminus of a variety of actin cytoskeleton-associated proteins. The headpiece domain of villin, a protein found in the actin bundles of the brush border epithelium, is of interest both as a compact F-actin binding domain and as a model folded protein. We have determined the high-resolution crystal structures of chicken villin headpiece (HP67) at 1.4 Angstrom resolution as well as two mutants, R37A and W64Y, at 1.45 and 1.5 Angstrom resolution, respectively. Replacement of R37 causes a 5-fold reduction in F-actin binding affinity in sedimentation assays. Replacement of W64 results in a much more drastic reduction in F-actin binding affinity without significant changes in headpiece structure or stability. The detailed comparison of these crystal structures with each other and to our previously determined NMR structures of HP67 and the 35-residue autonomously folding subdomain in villin headpiece, HP35, provides the details of the headpiece fold and further defines the F-actin binding site of villin-type headpiece domains.

  3. In vivo dynamics of the F-actin-binding protein neurabin-II.

    PubMed Central

    Stephens, D J; Banting, G

    2000-01-01

    Neurabin-II (spinophilin) is a ubiquitously expressed F-actin-binding protein containing an N-terminal actin-binding domain, a PDZ (PSD95/discs large/ZO-1) domain and a C-terminal domain predicted to form a coiled-coil structure. We have stably expressed a green fluorescent protein (GFP)-tagged version of neurabin-II in PC12 cells, and characterized the in vivo dynamics of this actin-binding protein using confocal fluorescence microscopy. We show that GFP-neurabin-II localizes to actin filaments, especially at cortical sites and areas underlying sites of active membrane remodelling. GFP-neurabin-II labels only a subset of F-actin within these cells, as indicated by rhodamine-phalloidin staining. Both actin filaments and small, highly motile structures within the cell body are seen. Photobleaching experiments show that GFP-neurabin-II also exhibits highly dynamic behaviour when bound to actin filaments. Latrunculin B treatment results in rapid relocalization of GFP-neurabin-II to the cytosol, whereas cytochalasin D treatment causes the collapse of GFP-neurabin-II fluorescence to intensely fluorescent foci of F-actin within the cell body. This collapse is reversed on cytochalasin D removal, recovery from which is greatly accelerated by stimulation of cells with epidermal growth factor (EGF). Furthermore, we show that this EGF-induced relocalization of GFP-neurabin-II is dependent on the activity of the small GTPase Rac1 but not the activity of ADP-ribosylation factor 6. PMID:10620493

  4. Modification of Cys-837 identifies an actin-binding site in the beta-propeller protein scruin.

    PubMed Central

    Sun, S; Footer, M; Matsudaira, P

    1997-01-01

    In the acrosomal process of Limulus sperm, the beta-propeller protein scruin cross-links actin into a crystalline bundle. To confirm that scruin has the topology of a beta-propeller protein and to understand how scruin binds actin, we compared the solvent accessibility of cysteine residues in scruin and the acrosomal process by chemical modification with (1,5-IAEDANS). In soluble scruin, the two most reactive cysteines of soluble scruin are C837 and C900, whereas C146, C333, and C683 are moderately reactive. This pattern of reactivity is consistent with the topology of a typical beta-propeller protein; all of the reactive cysteines map to putative loops and turns whereas the unreactive cysteines lie within the predicted interior of the protein. The chemical reactivities of cysteine in the acrosomal process implicate C837 at an actin-binding site. In contrast to soluble scruin, in the acrosomal process, C837 is completely unreactive while the other cysteines become less reactive. Binding studies of chemically modified scruin correlate the extent of modification at C837 with the extent of inhibition of actin binding. Furthermore, peptides corresponding to residues flanking C837 bind actin and narrow a possible actin-binding region to a KQK sequence. On the basis of these studies, our results suggest that an actin-binding site lies in the C-terminal domain of scruin and involves a putative loop defined by C837. Images PMID:9188095

  5. Concentration profiles of actin-binding molecules in lamellipodia

    NASA Astrophysics Data System (ADS)

    Falcke, Martin

    2016-04-01

    Motile cells form lamellipodia in the direction of motion, which are flat membrane protrusions containing an actin filament network. The network flows rearward relative to the leading edge of the lamellipodium due to actin polymerization at the front. Thus, actin binding molecules are subject to transport towards the rear of the cell in the bound state and diffuse freely in the unbound state. We analyze this reaction-diffusion-advection process with respect to the concentration profiles of these species and provide an analytic approximation for them. Network flow may cause a depletion zone of actin binding molecules close to the leading edge. The existence of such zone depends on the free molecule concentration in the cell body, on the ratio of the diffusion length to the distance bound molecules travel rearward with the flow before dissociating, and the ratio of the diffusion length to the width of the region with network flow and actin binding. Our calculations suggest the existence of depletion zones for the F-actin cross-linkers filamin and α-actinin in fish keratocytes (and other cell types), which is in line with the small elastic moduli of the F-actin network close to the leading edge found in measurements of the force motile cells are able to exert.

  6. Human endothelial actin-binding protein (ABP-280, nonmuscle filamin): a molecular leaf spring

    PubMed Central

    1990-01-01

    Actin-binding protein (ABP-280, nonmuscle filamin) is a ubiquitous dimeric actin cross-linking phosphoprotein of peripheral cytoplasm, where it promotes orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins. The complete nucleotide sequence of human endothelial cell ABP cDNA predicts a polypeptide subunit chain of 2,647 amino acids, corresponding to 280 kD, also the mass derived from physical measurements of the native protein. The actin-binding domain is near the amino-terminus of the subunit where the amino acid sequence is similar to other actin filament binding proteins, including alpha-actinin, beta-spectrin, dystrophin, and Dictyostelium abp-120. The remaining 90% of the sequence comprises 24 repeats, each approximately 96 residues long, predicted to have stretches of beta-sheet secondary structure interspersed with turns. The first 15 repeats may have substantial intrachain hydrophobic interactions and overlap in a staggered fashion to yield a backbone with mechanical resilience. Sequence insertions immediately before repeats 16 and 24 predict two hinges in the molecule near points where rotary-shadowed molecules appear to swivel in electron micrographs. Both putative hinge regions are susceptible to cleavage by proteases and the second also contains the site that binds the platelet glycoprotein Ib/IX complex. Phosphorylation consensus sequences are also located in the hinges or near them. Degeneracy within every even- numbered repeat between 16 and 24 and the insertion before repeat 24 may convert interactions within chains to interactions between chains to account for dimer formation within a domain of 7 kD at the carboxy- terminus. The structure of ABP dimers resembles a leaf spring. Interchain interactions hold the leaves firmly together at one end, whereas intrachain hydrophobic bonds reinforce the arms of the spring where the leaves diverge, making it sufficiently stiff to promote high- angle branching of actin

  7. EhNCABP166: a nucleocytoplasmic actin-binding protein from Entamoeba histolytica.

    PubMed

    Campos-Parra, A D; Hernández-Cuevas, N A; Hernandez-Rivas, R; Vargas, M

    2010-07-01

    The actin cytoskeleton consists of multiple actin binding proteins (ABPs) that participate cooperatively in different cellular functions such as the maintenance of polarity and cell motility as well as the invasion of target cells and regulation of gene expression, among others. Due to the important role of ABPs in the pathogenesis of Entamoeba histolytica, the role of a new nucleocytoplasmic ABP from E. histolytica named EhNCABP166 was investigated. The EhNCABP166 gene encodes a protein with an estimated molecular weight of 166kDa. Structurally, this peptide is composed of two CH domains arranged in tandem at the N-terminus of the protein, followed by an alpha-helical region containing a number of different domains with a low level of homology. Two (Bin1/Amphiphysin/Rvs167) (BAR) domains, one GTPase-binding/formin 3 homology (GBD/FH3) domain, three Bcl2-associated athanogene (BAG) domains, one basic-leucine zipper (bZIP) domain and one poly(A)-binding protein C-terminal (PABC) domain were also present. Molecular and biochemical studies showed that the EhNCABP166 protein is transcribed and translated in trophozoites of E. histolytica. It was also shown that the CH domains are functional and bind to F-actin, whereas the BAR and GBD/FH3 domains interact in vitro and in vivo with different families of GTPases such as Rho and Ras, and with different phosphoinositides. These findings suggest that these domains have the conserved functional properties described in other eukaryotic systems. These domains also interacted with additional GTPase and lipid targets that have not been previously described. Finally, cellular studies showed that EhNCABP166 is localized to the cytoplasm and nucleus of E. histolytica and that it has an important role in phagocytosis, proliferation, and motility of E. histolytica.

  8. Arabidopsis AtADF1 is functionally affected by mutations on actin binding sites.

    PubMed

    Dong, Chun-Hai; Tang, Wei-Ping; Liu, Jia-Yao

    2013-03-01

    The plant actin depolymerizing factor (ADF) binds to both monomeric and filamentous actin, and is directly involved in the depolymerization of actin filaments. To better understand the actin binding sites of the Arabidopsis thaliana L. AtADF1, we generated mutants of AtADF1 and investigated their functions in vitro and in vivo. Analysis of mutants harboring amino acid substitutions revealed that charged residues (Arg98 and Lys100) located at the α-helix 3 and forming an actin binding site together with the N-terminus are essential for both G- and F-actin binding. The basic residues on the β-strand 5 (K82/A) and the α-helix 4 (R135/A, R137/A) form another actin binding site that is important for F-actin binding. Using transient expression of CFP-tagged AtADF1 mutant proteins in onion (Allium cepa) peel epidermal cells and transgenic Arabidopsis thaliana L. plants overexpressing these mutants, we analyzed how these mutant proteins regulate actin organization and affect seedling growth. Our results show that the ADF mutants with a lower affinity for actin filament binding can still be functional, unless the affinity for actin monomers is also affected. The G-actin binding activity of the ADF plays an essential role in actin binding, depolymerization of actin polymers, and therefore in the control of actin organization. PMID:23190411

  9. The evolution of the actin binding NET superfamily

    PubMed Central

    Hawkins, Timothy J.; Deeks, Michael J.; Wang, Pengwei; Hussey, Patrick J.

    2014-01-01

    The Arabidopsis Networked (NET) superfamily are plant-specific actin binding proteins which specifically label different membrane compartments and identify specialized sites of interaction between actin and membranes unique to plants. There are 13 members of the superfamily in Arabidopsis, which group into four distinct clades or families. NET homologs are absent from the genomes of metazoa and fungi; furthermore, in plantae, NET sequences are also absent from the genome of mosses and more ancient extant plant clades. A single family of the NET proteins is found encoded in the club moss genome, an extant species of the earliest vascular plants. Gymnosperms have examples from families 4 and 3, with a hybrid form of NET1 and 2 which shows characteristics of both NET1 and NET2. In addition to NET3 and 4 families, the NET1 and pollen-expressed NET2 families are found only as independent sequences in Angiosperms. This is consistent with the divergence of reproductive actin. The four families are conserved across Monocots and Eudicots, with the numbers of members of each clade expanding at this point, due, in part, to regions of genome duplication. Since the emergence of the NET superfamily at the dawn of vascular plants, they have continued to develop and diversify in a manner which has mirrored the divergence and increasing complexity of land-plant species. PMID:24926301

  10. The evolution of the actin binding NET superfamily.

    PubMed

    Hawkins, Timothy J; Deeks, Michael J; Wang, Pengwei; Hussey, Patrick J

    2014-01-01

    The Arabidopsis Networked (NET) superfamily are plant-specific actin binding proteins which specifically label different membrane compartments and identify specialized sites of interaction between actin and membranes unique to plants. There are 13 members of the superfamily in Arabidopsis, which group into four distinct clades or families. NET homologs are absent from the genomes of metazoa and fungi; furthermore, in plantae, NET sequences are also absent from the genome of mosses and more ancient extant plant clades. A single family of the NET proteins is found encoded in the club moss genome, an extant species of the earliest vascular plants. Gymnosperms have examples from families 4 and 3, with a hybrid form of NET1 and 2 which shows characteristics of both NET1 and NET2. In addition to NET3 and 4 families, the NET1 and pollen-expressed NET2 families are found only as independent sequences in Angiosperms. This is consistent with the divergence of reproductive actin. The four families are conserved across Monocots and Eudicots, with the numbers of members of each clade expanding at this point, due, in part, to regions of genome duplication. Since the emergence of the NET superfamily at the dawn of vascular plants, they have continued to develop and diversify in a manner which has mirrored the divergence and increasing complexity of land-plant species.

  11. The evolution of the actin binding NET superfamily.

    PubMed

    Hawkins, Timothy J; Deeks, Michael J; Wang, Pengwei; Hussey, Patrick J

    2014-01-01

    The Arabidopsis Networked (NET) superfamily are plant-specific actin binding proteins which specifically label different membrane compartments and identify specialized sites of interaction between actin and membranes unique to plants. There are 13 members of the superfamily in Arabidopsis, which group into four distinct clades or families. NET homologs are absent from the genomes of metazoa and fungi; furthermore, in plantae, NET sequences are also absent from the genome of mosses and more ancient extant plant clades. A single family of the NET proteins is found encoded in the club moss genome, an extant species of the earliest vascular plants. Gymnosperms have examples from families 4 and 3, with a hybrid form of NET1 and 2 which shows characteristics of both NET1 and NET2. In addition to NET3 and 4 families, the NET1 and pollen-expressed NET2 families are found only as independent sequences in Angiosperms. This is consistent with the divergence of reproductive actin. The four families are conserved across Monocots and Eudicots, with the numbers of members of each clade expanding at this point, due, in part, to regions of genome duplication. Since the emergence of the NET superfamily at the dawn of vascular plants, they have continued to develop and diversify in a manner which has mirrored the divergence and increasing complexity of land-plant species. PMID:24926301

  12. Control of actin-based motility through localized actin binding.

    PubMed

    Banigan, Edward J; Lee, Kun-Chun; Liu, Andrea J

    2013-12-01

    A wide variety of cell biological and biomimetic systems use actin polymerization to drive motility. It has been suggested that an object such as a bacterium can propel itself by self-assembling a high concentration of actin behind it, if it is repelled by actin. However, it is also known that it is essential for the moving object to bind actin. Therefore, a key question is how the actin tail can propel an object when it both binds and repels the object. We present a physically consistent Brownian dynamics model for actin-based motility that includes the minimal components of the dendritic nucleation model and allows for both attractive and repulsive interactions between actin and a moveable disc. We find that the concentration gradient of filamentous actin generated by polymerization is sufficient to propel the object, even with moderately strong binding interactions. Additionally, actin binding can act as a biophysical cap, and may directly control motility through modulation of network growth. Overall, this mechanism is robust in that it can drive motility against a load up to a stall pressure that depends on the Young's modulus of the actin network and can explain several aspects of actin-based motility.

  13. MARCKS is a natively unfolded protein with an inaccessible actin-binding site: evidence for long-range intramolecular interactions.

    PubMed

    Tapp, Hazel; Al-Naggar, Iman M; Yarmola, Elena G; Harrison, Alexis; Shaw, Gerry; Edison, Arthur S; Bubb, Michael R

    2005-03-18

    Myristoylated alanine-rich C kinase substrate (MARCKS) is an unfolded protein that contains well characterized actin-binding sites within the phosphorylation site domain (PSD), yet paradoxically, we now find that intact MARCKS does not bind to actin. Intact MARCKS also does not bind as well to calmodulin as does the PSD alone. Myristoylation at the N terminus alters how calmodulin binds to MARCKS, implying that, despite its unfolded state, the distant N terminus influences binding events at the PSD. We show that the free PSD binds with site specificity to MARCKS, suggesting that long-range intramolecular interactions within MARCKS are also possible. Because of the unusual primary sequence of MARCKS with an overall isoelectric point of 4.2 yet a very basic PSD (overall charge of +13), we speculated that ionic interactions between oppositely charged domains of MARCKS were responsible for long-range interactions within MARCKS that sterically influence binding events at the PSD and that explain the observed differences between properties of the PSD and MARCKS. Consistent with this hypothesis, chemical modifications of MARCKS that neutralize negatively charged residues outside of the PSD allow the PSD to bind to actin and increase the affinity of MARCKS for calmodulin. Similarly, both myristoylation of MARCKS and cleavage of MARCKS by calpain are shown to increase the availability of the PSD so as to activate its actin-binding activity. Because abundant evidence supports the conclusion that MARCKS is an important protein in regulating actin dynamics, our data imply that post-translational modifications of MARCKS are necessary and sufficient to regulate actin-binding activity. PMID:15640140

  14. Polycystin-2 (TRPP2) Regulation by Ca2+ Is Effected and Diversified by Actin-Binding Proteins

    PubMed Central

    Cantero, María del Rocío; Cantiello, Horacio F.

    2015-01-01

    Calcium regulation of Ca2+-permeable ion channels is an important mechanism in the control of cell function. Polycystin-2 (PC2, TRPP2), a member of the transient receptor potential superfamily, is a nonselective cation channel with Ca2+ permeability. The molecular mechanisms associated with PC2 regulation by Ca2+ remain ill-defined. We recently demonstrated that PC2 from human syncytiotrophoblast (PC2hst) but not the in vitro translated protein (PC2iv), functionally responds to changes in intracellular (cis) Ca2+. In this study we determined the regulatory effect(s) of Ca2+-sensitive and -insensitive actin-binding proteins (ABPs) on PC2iv channel function in a lipid bilayer system. The actin-bundling protein α-actinin increased PC2iv channel function in the presence of cis Ca2+, although instead was inhibitory in its absence. Conversely, filamin that shares actin-binding domains with α-actinin had a strong inhibitory effect on PC2iv channel function in the presence, but no effect in the absence of cis Ca2+. Gelsolin stimulated PC2iv channel function in the presence, but not the absence of cis Ca2+. In contrast, profilin that shares actin-binding domains with gelsolin, significantly increased PC2iv channel function both in the presence and absence of Ca2+. The distinct effect(s) of the ABPs on PC2iv channel function demonstrate that Ca2+ regulation of PC2 is actually mediated by direct interaction(s) with structural elements of the actin cytoskeleton. These data indicate that specific ABP-PC2 complexes would confer distinct Ca2+-sensitive properties to the channel providing functional diversity to the cytoskeletal control of transient receptor potential channel regulation. PMID:25954877

  15. Identification of Actin-Binding Proteins from Maize Pollen

    SciTech Connect

    Staiger, C.J.

    2004-01-13

    Specific Aims--The goal of this project was to gain an understanding of how actin filament organization and dynamics are controlled in flowering plants. Specifically, we proposed to identify unique proteins with novel functions by investigating biochemical strategies for the isolation and characterization of actin-binding proteins (ABPs). In particular, our hunt was designed to identify capping proteins and nucleation factors. The specific aims included: (1) to use F-actin affinity chromatography (FAAC) as a general strategy to isolate pollen ABPs (2) to produce polyclonal antisera and perform subcellular localization in pollen tubes (3) to isolate cDNA clones for the most promising ABPs (4) to further purify and characterize ABP interactions with actin in vitro. Summary of Progress By employing affinity chromatography on F-actin or DNase I columns, we have identified at least two novel ABPs from pollen, PrABP80 (gelsolin-like) and ZmABP30, We have also cloned and expressed recombinant protein, as well as generated polyclonal antisera, for 6 interesting ABPs from Arabidopsis (fimbrin AtFIM1, capping protein a/b (AtCP), adenylyl cyclase-associated protein (AtCAP), AtCapG & AtVLN1). We performed quantitative analyses of the biochemical properties for two of these previously uncharacterized ABPs (fimbrin and capping protein). Our studies provide the first evidence for fimbrin activity in plants, demonstrate the existence of barbed-end capping factors and a gelsolin-like severing activity, and provide the quantitative data necessary to establish and test models of F-actin organization and dynamics in plant cells.

  16. NAC1 is an actin-binding protein that is essential for effective cytokinesis in cancer cells.

    PubMed

    Yap, Kai Lee; Fraley, Stephanie I; Thiaville, Michelle M; Jinawath, Natini; Nakayama, Kentaro; Wang, Jianlong; Wang, Tian-Li; Wirtz, Denis; Shih, Ie-Ming

    2012-08-15

    NAC1 is a transcriptional corepressor protein that is essential to sustain cancer cell proliferation and migration. However, the underlying molecular mechanisms of NAC1 function in cancer cells remain unknown. In this study, we show that NAC1 functions as an actin monomer-binding protein. The conserved BTB protein interaction domain in NAC1 is the minimal region for actin binding. Disrupting NAC1 complex function by dominant-negative or siRNA strategies reduced cell retraction and abscission during late-stage cytokinesis, causing multinucleation in cancer cells. In Nac1-deficient murine fibroblasts, restoring NAC1 expression was sufficient to partially avert multinucleation. We found that siRNA-mediated silencing of the actin-binding protein profilin-1 in cancer cells caused a similar multinucleation phenotype and that NAC1 modulated the binding of actin to profillin-1. Taken together, our results indicate that the NAC1/actin/profilin-1 complex is crucial for cancer cell cytokinesis, with a variety of important biologic and clinical implications.

  17. Technical advance: identification of plant actin-binding proteins by F-actin affinity chromatography

    NASA Technical Reports Server (NTRS)

    Hu, S.; Brady, S. R.; Kovar, D. R.; Staiger, C. J.; Clark, G. B.; Roux, S. J.; Muday, G. K.

    2000-01-01

    Proteins that interact with the actin cytoskeleton often modulate the dynamics or organization of the cytoskeleton or use the cytoskeleton to control their localization. In plants, very few actin-binding proteins have been identified and most are thought to modulate cytoskeleton function. To identify actin-binding proteins that are unique to plants, the development of new biochemical procedures will be critical. Affinity columns using actin monomers (globular actin, G-actin) or actin filaments (filamentous actin, F-actin) have been used to identify actin-binding proteins from a wide variety of organisms. Monomeric actin from zucchini (Cucurbita pepo L.) hypocotyl tissue was purified to electrophoretic homogeneity and shown to be native and competent for polymerization to actin filaments. G-actin, F-actin and bovine serum albumin affinity columns were prepared and used to separate samples enriched in either soluble or membrane-associated actin-binding proteins. Extracts of soluble actin-binding proteins yield distinct patterns when eluted from the G-actin and F-actin columns, respectively, leading to the identification of a putative F-actin-binding protein of approximately 40 kDa. When plasma membrane-associated proteins were applied to these columns, two abundant polypeptides eluted selectively from the F-actin column and cross-reacted with antiserum against pea annexins. Additionally, a protein that binds auxin transport inhibitors, the naphthylphthalamic acid binding protein, which has been previously suggested to associate with the actin cytoskeleton, was eluted in a single peak from the F-actin column. These experiments provide a new approach that may help to identify novel actin-binding proteins from plants.

  18. Actin-binding proteins: the long road to understanding the dynamic landscape of cellular actin networks.

    PubMed

    Lappalainen, Pekka

    2016-08-15

    The actin cytoskeleton supports a vast number of cellular processes in nonmuscle cells. It is well established that the organization and dynamics of the actin cytoskeleton are controlled by a large array of actin-binding proteins. However, it was only 40 years ago that the first nonmuscle actin-binding protein, filamin, was identified and characterized. Filamin was shown to bind and cross-link actin filaments into higher-order structures and contribute to phagocytosis in macrophages. Subsequently many other nonmuscle actin-binding proteins were identified and characterized. These proteins regulate almost all steps of the actin filament assembly and disassembly cycles, as well as the arrangement of actin filaments into diverse three-dimensional structures. Although the individual biochemical activities of most actin-regulatory proteins are relatively well understood, knowledge of how these proteins function together in a common cytoplasm to control actin dynamics and architecture is only beginning to emerge. Furthermore, understanding how signaling pathways and mechanical cues control the activities of various actin-binding proteins in different cellular, developmental, and pathological processes will keep researchers busy for decades. PMID:27528696

  19. Functional characterization of protein 4.1 homolog in amphioxus: defining a cryptic spectrin-actin-binding site.

    PubMed

    Wang, Lixia; Wang, Yuan; Li, Zhaohe; Gao, Zhan; Zhang, Shicui

    2013-10-07

    Vertebrate 4.1 proteins have a spectrin-actin-binding (SAB) domain, which is lacking in all the invertebrate 4.1 proteins indentified so far, and it was therefore proposed that the SAB domain emerged with the advent of vertebrates during evolution. Here we demonstrated for the first time that amphioxus (an invertebrate chordate) protein 4.1, though lacking a recognizable SAB, was able to bind both spectrin and actin, with a binding capacity comparable to that of human protein 4.1. Detailed structure-activity analyses revealed that the unique domain U2/3 was a newly identified SAB-like domain capable of interacting with spectrin and actin, suggesting the presence of a "cryptic" SAB domain in amphioxus 4.1 protein. We also showed that amphioxus 4.1 protein gene was the common ancestor of vertebrate 4.1 protein genes, from which 4.1R, 4.1N, 4.1G, and 4.1B genes originated. This work will encourage further study on the structure-activity of invertebrate 4.1 protein and its interacting proteins.

  20. Functional characterization of protein 4.1 homolog in amphioxus: defining a cryptic spectrin-actin-binding site.

    PubMed

    Wang, Lixia; Wang, Yuan; Li, Zhaohe; Gao, Zhan; Zhang, Shicui

    2013-01-01

    Vertebrate 4.1 proteins have a spectrin-actin-binding (SAB) domain, which is lacking in all the invertebrate 4.1 proteins indentified so far, and it was therefore proposed that the SAB domain emerged with the advent of vertebrates during evolution. Here we demonstrated for the first time that amphioxus (an invertebrate chordate) protein 4.1, though lacking a recognizable SAB, was able to bind both spectrin and actin, with a binding capacity comparable to that of human protein 4.1. Detailed structure-activity analyses revealed that the unique domain U2/3 was a newly identified SAB-like domain capable of interacting with spectrin and actin, suggesting the presence of a "cryptic" SAB domain in amphioxus 4.1 protein. We also showed that amphioxus 4.1 protein gene was the common ancestor of vertebrate 4.1 protein genes, from which 4.1R, 4.1N, 4.1G, and 4.1B genes originated. This work will encourage further study on the structure-activity of invertebrate 4.1 protein and its interacting proteins. PMID:24096627

  1. Target-specific cytotoxic effects on HER2-expressing cells by the tripartite fusion toxin ZHER2:2891-ABD-PE38X8, including a targeting affibody molecule and a half-life extension domain.

    PubMed

    Liu, Hao; Seijsing, Johan; Frejd, Fredrik Y; Tolmachev, Vladimir; Gräslund, Torbjörn

    2015-08-01

    Development of cancer treatment regimens including immunotoxins is partly hampered by their immunogenicity. Recently, deimmunized versions of toxins have been described, potentially being better suited for translation to the clinic. In this study, a recombinant tripartite fusion toxin consisting of a deimmunized version of exotoxin A from Pseudomonas aeruginosa (PE38) genetically fused to an affibody molecule specifically interacting with the human epidermal growth factor receptor 2 (HER2), and also an albumin binding domain (ABD) for half-life extension, has been produced and characterized in terms of functionality of the three moieties. Biosensor based assays showed that the fusion toxin was able to interact with human and mouse serum albumin, but not with bovine serum albumin and that it interacted with HER2 (KD=5 nM). Interestingly, a complex of the fusion toxin and human serum albumin also interacted with HER2 but with a somewhat weaker affinity (KD=12 nM). The IC50-values of the fusion toxin ranged from 6 to 300 pM on SKOV-3, SKBR-3 and A549 cells and was lower for cells with higher surface densities of HER2. The fusion toxin was found specific for HER2 as shown by blocking available HER2 receptors with free affibody molecule before subjecting the cells to the toxin. Analysis of contact time showed that 10 min was sufficient to kill 50% of the cells. In conclusion, all three regions of the fusion toxin were found to be functional.

  2. Interactions of actin, myosin, and an actin-binding protein of chronic myelogenous leukemia leukocytes.

    PubMed Central

    Boxer, L A; Stossel, T P

    1976-01-01

    Actin, myosin, and a high molecular weight actin-binding protein were purified from chronic myelogenous leukemia (CML) leukocytes. CML leukocyte actin resembled skeletal muscle and other cytoplasmic actins by its subunit molecular weight, by its ability to polymerize in the presence of salts, and to activate the Mg2+-ATPase activity of rabbit skeletal muscle myosin. CML leukocyte myosin was similar to other vertebrate cytoplasmic myosins in having heavy chains and two light subunits. However, its apparent heavy-chain molecular weight and Stokes radius suggested that it was variably degraded during purification. Purified CML leukocyte myosin had average specific EDTA- AND Ca2+-activated ATPase activities of 125 and 151 nmol Pi released/mg protein per min, respectively and low specific Mg2+-ATPase activity. The Mg2+-ATPase activity of CML myosin was increased 200-fold by rabbit skeletal muscle F-actin, but the specific activity relative to that of actin-activated rabbit skeletal muscle myosin was low. CML leukocyte myosin, like other vertebrate cytoplasmic myosins, formed filaments in 0.1 M KCl solutions. Reduced and denatured CML leukocyte-actin-binding protein had a single high molecular weight subunit like a recently described actin-binding protein of rabbit pulmonary macrophages which promotes the polymerization and gelation of actin. Cytoplasmic extracts of CML leukocytes prepared with ice-cold 0.34-M sucrose solutions containing Mg2+-ATP, dithiothreitol, and EDTA at pH 7.0 underwent rapid gelation when warmed to 25 degrees C. Initially, the gel could be liquified by cooling to ice-bath temperature. With time, warmed cytoplasmic extract gels shrunk ("contracted") into aggregates. The following findings indicated that CML leukocyte actin-binding protein promoted the temperature-dependent gelation of actin in the cytoplasmic extracts and that CML leukocyte myosin was involved in the contraction of the actin gels: (a) Cytoplasmic extract gels initially contained

  3. Switch II mutants reveal coupling between the nucleotide- and actin-binding regions in myosin V.

    PubMed

    Trivedi, Darshan V; David, Charles; Jacobs, Donald J; Yengo, Christopher M

    2012-06-01

    Conserved active-site elements in myosins and other P-loop NTPases play critical roles in nucleotide binding and hydrolysis; however, the mechanisms of allosteric communication among these mechanoenzymes remain unresolved. In this work we introduced the E442A mutation, which abrogates a salt-bridge between switch I and switch II, and the G440A mutation, which abolishes a main-chain hydrogen bond associated with the interaction of switch II with the γ phosphate of ATP, into myosin V. We used fluorescence resonance energy transfer between mant-labeled nucleotides or IAEDANS-labeled actin and FlAsH-labeled myosin V to examine the conformation of the nucleotide- and actin-binding regions, respectively. We demonstrate that in the absence of actin, both the G440A and E442A mutants bind ATP with similar affinity and result in only minor alterations in the conformation of the nucleotide-binding pocket (NBP). In the presence of ADP and actin, both switch II mutants disrupt the formation of a closed NBP actomyosin.ADP state. The G440A mutant also prevents ATP-induced opening of the actin-binding cleft. Our results indicate that the switch II region is critical for stabilizing the closed NBP conformation in the presence of actin, and is essential for communication between the active site and actin-binding region.

  4. Switch II Mutants Reveal Coupling between the Nucleotide- and Actin-Binding Regions in Myosin V

    PubMed Central

    Trivedi, Darshan V.; David, Charles; Jacobs, Donald J.; Yengo, Christopher M.

    2012-01-01

    Conserved active-site elements in myosins and other P-loop NTPases play critical roles in nucleotide binding and hydrolysis; however, the mechanisms of allosteric communication among these mechanoenzymes remain unresolved. In this work we introduced the E442A mutation, which abrogates a salt-bridge between switch I and switch II, and the G440A mutation, which abolishes a main-chain hydrogen bond associated with the interaction of switch II with the γ phosphate of ATP, into myosin V. We used fluorescence resonance energy transfer between mant-labeled nucleotides or IAEDANS-labeled actin and FlAsH-labeled myosin V to examine the conformation of the nucleotide- and actin-binding regions, respectively. We demonstrate that in the absence of actin, both the G440A and E442A mutants bind ATP with similar affinity and result in only minor alterations in the conformation of the nucleotide-binding pocket (NBP). In the presence of ADP and actin, both switch II mutants disrupt the formation of a closed NBP actomyosin.ADP state. The G440A mutant also prevents ATP-induced opening of the actin-binding cleft. Our results indicate that the switch II region is critical for stabilizing the closed NBP conformation in the presence of actin, and is essential for communication between the active site and actin-binding region. PMID:22713570

  5. Moesin, ezrin, and p205 are actin-binding proteins associated with neutrophil plasma membranes.

    PubMed Central

    Pestonjamasp, K; Amieva, M R; Strassel, C P; Nauseef, W M; Furthmayr, H; Luna, E J

    1995-01-01

    Actin-binding proteins in bovine neutrophil plasma membranes were identified using blot overlays with 125I-labeled F-actin. Along with surface-biotinylated proteins, membranes were enriched in major actin-binding polypeptides of 78, 81, and 205 kDa. Binding was specific for F-actin because G-actin did not bind. Further, unlabeled F-actin blocked the binding of 125I-labeled F-actin whereas other acidic biopolymers were relatively ineffective. Binding also was specifically inhibited by myosin subfragment 1, but not by CapZ or plasma gelsolin, suggesting that the membrane proteins, like myosin, bind along the sides of the actin filaments. The 78- and 81-kDa polypeptides were identified as moesin and ezrin, respectively, by co-migration on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoprecipitation with antibodies specific for moesin and ezrin. Although not present in detectable amounts in bovine neutrophils, radixin (a third and closely related member of this gene family) also bound 125I-labeled F-actin on blot overlays. Experiments with full-length and truncated bacterial fusion proteins localized the actin-binding site in moesin to the extreme carboxy terminus, a highly conserved sequence. Immunofluorescence micrographs of permeabilized cells and cell "footprints" showed moesin co-localization with actin at the cytoplasmic surface of the plasma membrane, consistent with a role as a membrane-actin-linking protein. Images PMID:7612961

  6. Purification and properties of a 90-kDa nuclear actin-binding protein.

    PubMed

    Yeoman, L C; Bremer, J W

    1986-04-01

    A 90 kDa actin-binding nuclear protein (ABNP) with a pI of 5.2 has been purified from the 0.7 M NaCl extracted residue fraction of chromatin prepared from Novikoff hepatoma cell nuclei. This residue fraction was previously shown to contain nuclear actin. Although twice the size, similar in pI, and similar in amino acid composition to actin, the tryptic peptide map for ABNP is distinct and contains the appropriate number of tyrosine-containing tryptic peptides for a protein of 90,000 molecular weight. A comparison of the amino acid composition of ABNP with those reported in the literature for gelsolin and villin, using a calculation of S delta Q as an indication of relatedness, results in values of 30 and 27, respectively. Actin-binding activity, however, was demonstrated for both crude and gel purified ABNP using a gel-overlay technique that employs 125I-G-actin to detect specific actin-binding proteins.

  7. 65-kilodalton protein phosphorylated by interleukin 2 stimulation bears two putative actin-binding sites and two calcium-binding sites

    SciTech Connect

    Zu, Youli; Shigesada, Katsuya; Hanaoka, Masao; Namba, Yuziro ); Nishida, Eisuke ); Kubota, Ichiro ); Kohno, Michiaki )

    1990-09-11

    The authors have previously characterized a 65-kilodalton protein (p65) as an interleukin 2 stimulated phosphoprotein in human T cells and showed that three endopeptide sequences of p65 are present in the sequence of l-plastin. In this paper, they present the complete primary structure of p65 based on the cDNA isolated from a human T lymphocyte (KUT-2) cDNA library. Analysis of p65 sequences and the amino acid composition of cleaved p65 N-terminal peptide indicated that the deduced p65 amino acid sequence exactly coincides with that of l-plastin over the C-terminal 580 residues and has a 57-residue extension at the N-terminus to l-plastin. Computer-assisted structural analysis revealed that p65 is a multidomain molecule involving at least three intriguing functional domains: two putative calcium-binding sites along the N-terminal 80 amino acid residues; a putative calmodulin-binding site following the calcium-binding region; and two tandem repeats of putative actin-binding domains in its middle and C-terminal parts, each containing approximately 240 amino acid residues. These results suggest that p65 belongs to actin-binding proteins.

  8. Resemblance of actin-binding protein/actin gels to covalently crosslinked networks

    NASA Astrophysics Data System (ADS)

    Janmey, Paul A.; Hvidt, Søren; Lamb, Jennifer; Stossel, Thomas P.

    1990-05-01

    THE maintainance of the shape of cells is often due to their surface elasticity, which arises mainly from an actin-rich cytoplasmic cortex1,2. On locomotion, phagocytosis or fission, however, these cells become partially fluid-like. The finding of proteins that can bind to actin and control the assembly of, or crosslink, actin filaments, and of intracellular messages that regulate the activities of some of these actin-binding proteins, indicates that such 'gel sol' transformations result from the rearrangement of cortical actin-rich networks3. Alternatively, on the basis of a study of the mechanical properties of mixtures of actin filaments and an Acanthamoeba actin-binding protein, α-actinin, it has been proposed that these transformations can be accounted for by rapid exchange of crosslinks between actin filaments4: the cortical network would be solid when the deformation rate is greater than the rate of crosslink exchange, but would deform or 'creep' when deformation is slow enough to permit crosslinker molecules to rearrange. Here we report, however, that mixtures of actin filaments and actin-binding protein (ABP), an actin crosslinking protein of many higher eukaryotes, form gels Theologically equivalent to covalently crosslinked networks. These gels do not creep in response to applied stress on a time scale compatible with most cell-surface movements. These findings support a more complex and controlled mechanism underlying the dynamic mechanical properties of cortical cytoplasm, and can explain why cells do not collapse under the constant shear forces that often exist in tissues.

  9. Functional Analysis of Actin-Binding Proteins in the Central Nervous System of Drosophila.

    PubMed

    He, Qi; Roblodowski, Christopher

    2016-01-01

    Using Drosophila actin-binding protein Dunc-115 as model system, this chapter describes a MARCM (mosaic analysis with a repressible cell marker)-based method for analyzing cytoskeletal components for their functions in the nervous system. Following a concise description about the principle, a step-by-step protocol is provided for generating the needed stocks and for histological analysis. Additional details and explanations have been given in the accompanying notes. Together, this should form a practical and sufficient recipe for performing at the single-cell-level loss-of-function and gain-of-function analyses of proteins associated with the cytoskeleton.

  10. Human RNASET2 derivatives as potential anti-angiogenic agents: actin binding sequence identification and characterization

    PubMed Central

    Nesiel-Nuttman, Liron; Doron, Shani; Schwartz, Betty; Shoseyov, Oded

    2015-01-01

    Human RNASET2 (hRNASET2) has been demonstrated to exert antiangiogenic and antitumorigenic effects independent of its ribonuclease capacity. We suggested that RNASET2 exerts its antiangiogenic and antitumorigenic activities via binding to actin and consequently inhibits cell motility. We focused herein on the identification of the actin binding site of hRNASET2 using defined sequences encountered within the whole hRNASET2 protein. For that purpose we designed 29 different hRNASET2-derived peptides. The 29 peptides were examined for their ability to bind immobilized actin. Two selected peptides-A103-Q159 consisting of 57 amino acids and peptide K108-K133 consisting of 26 amino acids were demonstrated to have the highest actin binding ability and concomitantly the most potent anti-angiogenic activity. Further analyses on the putative mechanisms associated with angiogenesis inhibition exerted by peptide K108-K133 involved its location during treatment within the HUVE cells. Peptide K108-K133 readily penetrates the cell membrane within 10 min of incubation. In addition, supplementation with angiogenin delays the entrance of peptide K108-K133 to the cell suggesting competition on the same cell internalization route. The peptide was demonstrated to co-localize with angiogenin, suggesting that both molecules bind analogous cellular epitopes, similar to our previously reported data for ACTIBIND and trT2-50. PMID:25815360

  11. Actin-Binding Protein 1 Regulates B Cell Receptor-Mediated Antigen Processing and Presentation in Response to B Cell Receptor Activation1

    PubMed Central

    Onabajo, Olusegun O.; Seeley, Margaret K.; Kale, Amruta; Qualmann, Britta; Kessels, Michael; Han, Jin; Tan, Tse-Hua; Song, Wenxia

    2010-01-01

    The BCR serves as both signal transducer and Ag transporter. Binding of Ags to the BCR induces signaling cascades and Ag processing and presentation, two essential cellular events for B cell activation. BCR-initiated signaling increases BCR-mediated Ag-processing efficiency by increasing the rate and specificity of Ag transport. Previous studies showed a critical role for the actin cytoskeleton in these two processes. In this study, we found that actin-binding protein 1 (Abp1/HIP-55/SH3P7) functioned as an actin-binding adaptor protein, coupling BCR signaling and Ag-processing pathways with the actin cytoskeleton. Gene knockout of Abp1 and overexpression of the Src homology 3 domain of Abp1 inhibited BCR-mediated Ag internalization, consequently reducing the rate of Ag transport to processing compartments and the efficiency of BCR-mediated Ag processing and presentation. BCR activation induced tyrosine phosphorylation of Abp1 and translocation of both Abp1 and dynamin 2 from the cytoplasm to plasma membrane, where they colocalized with the BCR and cortical F-actin. Mutations of the two tyrosine phosphorylation sites of Abp1 and depolymerization of the actin cytoskeleton interfered with BCR-induced Abp1 recruitment to the plasma membrane. The inhibitory effect of a dynamin proline-rich domain deletion mutant on the recruitment of Abp1 to the plasma membrane, coimmunoprecipitation of dynamin with Abp1, and coprecipitation of Abp1 with GST fusion of the dyanmin proline-rich domain demonstrate the interaction of Abp1 with dynamin 2. These results demonstrate that the BCR regulates the function of Abp1 by inducing Abp1 phosphorylation and actin cytoskeleton rearrangement, and that Abp1 facilitates BCR-mediated Ag processing by simultaneously interacting with dynamin and the actin cytoskeleton. The Journal of Immunology, 2008, 180: 6685–6695. PMID:18453588

  12. Endothelial actin-binding proteins and actin dynamics in leukocyte transendothelial migration.

    PubMed

    Schnoor, Michael

    2015-04-15

    The endothelium is the first barrier that leukocytes have to overcome during recruitment to sites of inflamed tissues. The leukocyte extravasation cascade is a complex multistep process that requires the activation of various adhesion molecules and signaling pathways, as well as actin remodeling, in both leukocytes and endothelial cells. Endothelial adhesion molecules, such as E-selectin or ICAM-1, are connected to the actin cytoskeleton via actin-binding proteins (ABPs). Although the contribution of receptor-ligand interactions to leukocyte extravasation has been studied extensively, the contribution of endothelial ABPs to the regulation of leukocyte adhesion and transendothelial migration remains poorly understood. This review focuses on recently published evidence that endothelial ABPs, such as cortactin, myosin, or α-actinin, regulate leukocyte extravasation by controlling actin dynamics, biomechanical properties of endothelia, and signaling pathways, such as GTPase activation, during inflammation. Thus, ABPs may serve as targets for novel treatment strategies for disorders characterized by excessive leukocyte recruitment.

  13. How actin binds and assembles onto plasma membranes from Dictyostelium discoideum

    PubMed Central

    1988-01-01

    We have shown previously (Schwartz, M. A., and E. J. Luna. 1986. J. Cell Biol. 102: 2067-2075) that actin binds with positive cooperativity to plasma membranes from Dictyostelium discoideum. Actin is polymerized at the membrane surface even at concentrations well below the critical concentration for polymerization in solution. Low salt buffer that blocks actin polymerization in solution also prevents actin binding to membranes. To further explore the relationship between actin polymerization and binding to membranes, we prepared four chemically modified actins that appear to be incapable of polymerizing in solution. Three of these derivatives also lost their ability to bind to membranes. The fourth derivative (EF actin), in which histidine-40 is labeled with ethoxyformic anhydride, binds to membranes with reduced affinity. Binding curves exhibit positive cooperativity, and cross- linking experiments show that membrane-bound actin is multimeric. Thus, binding and polymerization are tightly coupled, and the ability of these membranes to polymerize actin is dramatically demonstrated. EF actin coassembles weakly with untreated actin in solution, but coassembles well on membranes. Binding by untreated actin and EF actin are mutually competitive, indicating that they bind to the same membrane sites. Hill plots indicate that an actin trimer is the minimum assembly state required for tight binding to membranes. The best explanation for our data is a model in which actin oligomers assemble by binding to clustered membrane sites with successive monomers on one side of the actin filament bound to the membrane. Individual binding affinities are expected to be low, but the overall actin-membrane avidity is high, due to multivalency. Our results imply that extracellular factors that cluster membrane proteins may create sites for the formation of actin nuclei and thus trigger actin polymerization in the cell. PMID:3392099

  14. Identification of a new actin binding surface on vinculin that mediates mechanical cell and focal adhesion properties

    PubMed Central

    Thompson, Peter M.; Tolbert, Caitlin E.; Shen, Kai; Kota, Pradeep; Palmer, Sean M.; Plevock, Karen M.; Orlova, Albina; Galkin, Vitold E.; Burridge, Keith; Egelman, Edward H.; Dokholyan, Nikolay V.; Superfine, Richard; Campbell, Sharon L.

    2014-01-01

    SUMMARY Vinculin, a cytoskeletal scaffold protein essential for embryogenesis and cardiovascular function, localizes to focal adhesions and adherens junctions, connecting cell surface receptors to the actin cytoskeleton. While vinculin interacts with many adhesion proteins, its interaction with filamentous actin regulates cell morphology, motility, and mechanotransduction. Disruption of this interaction lowers cell traction forces and enhances actin flow rates. Although a model for the vinculin:actin complex exists, we recently identified actin-binding deficient mutants of vinculin outside sites predicted to bind actin, and developed an alternative model to better define this novel actin-binding surface, using negative-stain EM, discrete molecular dynamics, and mutagenesis. Actin-binding deficient vinculin variants expressed in vinculin knockout fibroblasts fail to rescue cell-spreading defects and reduce cellular response to external force. These findings highlight the importance of this new actin-binding surface and provide the molecular basis for elucidating additional roles of this interaction, including actin-induced conformational changes which promote actin bundling. PMID:24685146

  15. Importance of internal regions and the overall length of tropomyosin for actin binding and regulatory function.

    PubMed

    Hitchcock-DeGregori, S E; Song, Y; Moraczewska, J

    2001-02-20

    Tropomyosin (Tm) binds along actin filaments, one molecule spanning four to seven actin monomers, depending on the isoform. Periodic repeats in the sequence have been proposed to correspond to actin binding sites. To learn the functional importance of length and the internal periods we made a series of progressively shorter Tms, deleting from two up to six of the internal periods from rat striated alpha-TM (dAc2--3, dAc2--4, dAc3--5, dAc2--5, dAc2--6, dAc1.5--6.5). Recombinant Tms (unacetylated) were expressed in Escherichia coli. Tropomyosins that are four or more periods long (dAc2--3, dAc2--4, and dAc3--5) bound well to F-actin with troponin (Tn). dAc2--5 bound weakly (with EGTA) and binding of shorter mutants was undetectable in any condition. Myosin S1-induced binding of Tm to actin in the tight Tm-binding "open" state did not correlate with actin binding. dAc3--5 and dAc2--5 did not bind to actin even when the filament was saturated with S1. In contrast, dAc2--3 and dAc2--4 did, like wild-type-Tm, requiring about 3 mol of S1/mol of Tm for half-maximal binding. The results show the critical importance of period 5 (residues 166--207) for myosin S1-induced binding. The Tms that bound to actin (dAc2--3, dAc2--4, and dAc3--5) all fully inhibited the actomyosin ATPase (+Tn) in EGTA. In the presence of Ca(2+), relief of inhibition by these Tms was incomplete. We conclude (1) four or more actin periods are required for Tm to bind to actin with reasonable affinity and (2) that the structural requirements of Tm for the transition of the regulated filament from the blocked-to-closed/open (relief of inhibition by Ca(2+)) and the closed-to-open states (strong Tm binding to actin-S1) are different. PMID:11329279

  16. The architecture of actin filaments and the ultrastructural location of actin-binding protein in the periphery of lung macrophages.

    PubMed

    Hartwig, J H; Shevlin, P

    1986-09-01

    A highly branched filament network is the principal structure in the periphery of detergent-extracted cytoskeletons of macrophages that have been spread on a surface and either freeze or critical point dried, and then rotary shadowed with platinum-carbon. This array of filaments completely fills lamellae extended from the cell and bifurcates to form 0.2-0.5 micron thick layers on the top and bottom of the cell body. Reaction of the macrophage cytoskeletons with anti-actin IgG and with anti-IgG bound to colloidal gold produces dense staining of these filaments, and incubation with myosin subfragment 1 uniformly decorates these filaments, identifying them as actin. 45% of the total cellular actin and approximately 70% of actin-binding protein remains in the detergent-insoluble cell residue. The soluble actin is not filamentous as determined by sedimentation analysis, the DNAase I inhibition assay, and electron microscopy, indicating that the cytoskeleton is not fragmented by detergent extraction. The spacing between the ramifications of the actin network is 94 +/- 47 nm and 118 +/- 72 nm in cytoskeletons prepared for electron microscopy by freeze drying and critical point drying, respectively. Free filament ends are rare, except for a few which project upward from the body of the network or which extend down to the substrate. Filaments of the network intersect predominantly at right angles to form either T-shaped and X-shaped overlaps having striking perpendicularity or else Y-shaped intersections composed of filaments intersecting at 120-130 degrees angles. The actin filament concentration in the lamellae is high, with an average value of 12.5 mg/ml. The concentration was much more uniform in freeze-dried preparations than in critical point-dried specimens, indicating that there is less collapse associated with the freezing technique. The orthogonal actin network of the macrophage cortical cytoplasm resembles actin gels made with actin-binding protein. Reaction of

  17. Regulation of blood-testis barrier by actin binding proteins and protein kinases

    PubMed Central

    Li, Nan; Tang, Elizabeth I.; Cheng, C. Yan

    2016-01-01

    The blood-testis barrier (BTB) is an important ultrastructure in the testis since the onset of spermatogenesis coincides with the establishment of a functional barrier in rodents and humans. It is also noted that a delay in the assembly of a functional BTB following treatment of neonatal rats with drugs such as diethylstilbestrol or adjudin also delays the first wave of spermiation. While the BTB is one of the tightest blood-tissue barriers, it undergoes extensive remodeling, in particular at stage VIII of the epithelial cycle to facilitate the transport of preleptotene spermatocytes connected in clones across the immunological barrier. Without this timely transport of preleptotene spermatocytes derived from type B spermatogonia, meiosis will be arrested, causing aspermatogenesis. Yet the biology and regulation of the BTB remains largely unexplored since the morphological studies in the 1970s. Recent studies, however, have shed new light on the biology of the BTB. Herein, we critically evaluate some of these findings, illustrating that the Sertoli cell BTB is regulated by actin binding proteins (ABPs), likely supported by non-receptor protein kinases, to modulate the organization of actin microfilament bundles at the site. Furthermore, microtubule (MT)-based cytoskeleton is also working in concert with the actin-based cytoskeleton to confer BTB dynamics. This timely review provides an update on the unique biology and regulation of the BTB based on the latest findings in the field, focusing on the role of ABPs and non-receptor protein kinases. PMID:26628556

  18. Analysis of the human cofilin 1 structure reveals conformational changes required for actin binding

    PubMed Central

    Klejnot, Marta; Gabrielsen, Mads; Cameron, Jenifer; Mleczak, Andrzej; Talapatra, Sandeep K.; Kozielski, Frank; Pannifer, Andrew; Olson, Michael F.

    2013-01-01

    The actin cytoskeleton is the chassis that gives a cell its shape and structure, and supplies the power for numerous dynamic processes including motility, endocytosis, intracellular transport and division. To perform these activities, the cytoskeleton undergoes constant remodelling and reorganization. One of the major actin-remodelling families are the cofilin proteins, made up of cofilin 1, cofilin 2 and actin-depolymerizing factor (ADF), which sever aged ADP-associated actin filaments to reduce filament length and provide new potential nucleation sites. Despite the significant interest in cofilin as a central node in actin-cytoskeleton dynamics, to date the only forms of cofilin for which crystal structures have been solved are from the yeast, Chromalveolata and plant kingdoms; none have previously been reported for an animal cofilin protein. Two distinct regions in animal cofilin are significantly larger than in the forms previously crystallized, suggesting that they would be uniquely organized. Therefore, it was sought to determine the structure of human cofilin 1 by X-ray crystallography to elucidate how it could interact with and regulate dynamic actin-cytoskeletal structures. Although wild-type human cofilin 1 proved to be recalcitrant, a C147A point mutant yielded crystals that diffracted to 2.8 Å resolution. These studies revealed how the actin-binding helix undergoes a conformational change that increases the number of potential hydrogen bonds available for substrate binding. PMID:23999301

  19. Redox-sensitive residue in the actin-binding interface of myosin.

    PubMed

    Moen, Rebecca J; Cornea, Sinziana; Oseid, Daniel E; Binder, Benjamin P; Klein, Jennifer C; Thomas, David D

    2014-10-24

    We have examined the chemical and functional reversibility of oxidative modification in myosin. Redox regulation has emerged as a crucial modulator of protein function, with particular relevance to aging. We previously identified a single methionine residue in Dictyostelium discoideum (Dicty) myosin II (M394, near the myosin cardiomyopathy loop in the actin-binding interface) that is functionally sensitive to oxidation. We now show that oxidation of M394 is reversible by methionine sulfoxide reductase (Msr), restoring actin-activated ATPase activity. Sequence alignment reveals that M394 of Dicty myosin II is a cysteine residue in all human isoforms of skeletal and cardiac myosin. Using Dicty myosin II as a model for site-specific redox sensitivity of this Cys residue, the M394C mutant can be glutathionylated in vitro, resulting in reversible inhibition of actin-activated ATPase activity, with effects similar to those of methionine oxidation at this site. This work illustrates the potential for myosin to function as a redox sensor in both non-muscle and muscle cells, modulating motility/contractility in response to oxidative stress. PMID:25264102

  20. Redox-sensitive residue in the actin-binding interface of myosin

    PubMed Central

    Moen, Rebecca J.; Cornea, Sinziana; Oseid, Daniel E.; Binder, Benjamin P.; Klein, Jennifer C.; Thomas, David D.

    2014-01-01

    We have examined the chemical and functional reversibility of oxidative modification in myosin. Redox regulation has emerged as a crucial modulator of protein function, with particular relevance to aging. We previously identified a single methionine residue in Dictyostelium discoideum (Dicty) myosin II (M394, near the myosin cardiomyopathy loop in the actin-binding interface) that is functionally sensitive to oxidation. We now show that oxidation of M394 is reversible by methionine sulfoxide reductase (Msr), restoring actin-activated ATPase activity. Sequence alignment reveals that M394 of Dicty myosin II is a cysteine residue in all human isoforms of skeletal and cardiac myosin. Using Dicty myosin II as a model for site-specific redox sensitivity of this Cys residue, the M394C mutant can be glutathionylated in vitro, resulting in reversible inhibition of actin-activated ATPase activity, with effects similar to those of methionine oxidation at this site. This work illustrates the potential for myosin to function as a redox sensor in both non-muscle and muscle cells, modulating motility/contractility in response to oxidative stress. PMID:25264102

  1. A second Las17 monomeric actin-binding motif functions in Arp2/3-dependent actin polymerization during endocytosis.

    PubMed

    Feliciano, Daniel; Tolsma, Thomas O; Farrell, Kristen B; Aradi, Al; Di Pietro, Santiago M

    2015-04-01

    During clathrin-mediated endocytosis (CME), actin assembly provides force to drive vesicle internalization. Members of the Wiskott-Aldrich syndrome protein (WASP) family play a fundamental role stimulating actin assembly. WASP family proteins contain a WH2 motif that binds globular actin (G-actin) and a central-acidic motif that binds the Arp2/3 complex, thus promoting the formation of branched actin filaments. Yeast WASP (Las17) is the strongest of five factors promoting Arp2/3-dependent actin polymerization during CME. It was suggested that this strong activity may be caused by a putative second G-actin-binding motif in Las17. Here, we describe the in vitro and in vivo characterization of such Las17 G-actin-binding motif (LGM) and its dependence on a group of conserved arginine residues. Using the yeast two-hybrid system, GST-pulldown, fluorescence polarization and pyrene-actin polymerization assays, we show that LGM binds G-actin and is necessary for normal Arp2/3-mediated actin polymerization in vitro. Live-cell fluorescence microscopy experiments demonstrate that LGM is required for normal dynamics of actin polymerization during CME. Further, LGM is necessary for normal dynamics of endocytic machinery components that are recruited at early, intermediate and late stages of endocytosis, as well as for optimal endocytosis of native CME cargo. Both in vitro and in vivo experiments show that LGM has relatively lower potency compared to the previously known Las17 G-actin-binding motif, WH2. These results establish a second G-actin-binding motif in Las17 and advance our knowledge on the mechanism of actin assembly during CME.

  2. Design, synthesis, and biological evaluation of simplified side chain hybrids of the potent actin binding polyketides rhizopodin and bistramide.

    PubMed

    Herkommer, Daniel; Dreisigacker, Sandra; Sergeev, Galina; Sasse, Florenz; Gohlke, Holger; Menche, Dirk

    2015-03-01

    The natural products rhizopodin and bistramide belong to an elite class of highly potent actin binding agents. They show powerful antiproliferative activities against a range of tumor cell lines, with IC50 values in the low-nanomolar range. At the molecular level they disrupt the actin cytoskeleton by binding specifically to a few critical sites of G-actin, resulting in actin filament stabilization. The important biological properties of rhizopodin and bistramide, coupled with their unique and intriguing molecular architectures, render them attractive compounds for further development. However, this is severely hampered by the structural complexity of these metabolites. We initiated an interdisciplinary approach at the interface between molecular modeling, organic synthesis, and chemical biology to support further biological applications. We also wanted to expand structure-activity relationship studies with the goal of accessing simplified analogues with potent biological properties. We report computational analyses of actin-inhibitor interactions involving molecular docking, validated on known actin binding ligands, that show a close match between the crystal and modeled structures. Based on these results, the ligand shape was simplified, and more readily accessible rhizopodin-bistramide mimetics were designed. A flexible and modular strategy was applied for the synthesis of these compounds, enabling diverse access to dramatically simplified rhizopodin-bistramide hybrids. This novel analogue class was analyzed for its antiproliferative and actin binding properties. PMID:25641798

  3. Early events of fertilization in sea urchin eggs are sensitive to actin-binding organic molecules.

    PubMed

    Chun, Jong T; Limatola, Nunzia; Vasilev, Filip; Santella, Luigia

    2014-08-01

    We previously demonstrated that many aspects of the intracellular Ca(2+) increase in fertilized eggs of starfish are significantly influenced by the state of the actin cytoskeleton. In addition, the actin cytoskeleton appeared to play comprehensive roles in modulating cortical granules exocytosis and sperm entry during the early phase of fertilization. In the present communication, we have extended our work to sea urchin which is believed to have bifurcated from the common ancestor in the phylogenetic tree some 500 million years ago. To corroborate our earlier findings in starfish, we have tested how the early events of fertilization in sea urchin eggs are influenced by four different actin-binding drugs that promote either depolymerization or stabilization of actin filaments. We found that all the actin drugs commonly blocked sperm entry in high doses and significantly reduced the speed of the Ca(2+) wave. At low doses, however, cytochalasin B and phalloidin increased the rate of polyspermy. Overall, certain aspects of Ca(2+) signaling in these eggs were in line with the morphological changes induced by the actin drugs. That is, the time interval between the cortical flash and the first Ca(2+) spot at the sperm interaction site (the latent period) was significantly prolonged in the eggs pretreated with cytochalasin B or latrunculin A, whereas the Ca(2+) decay kinetics after the peak was specifically attenuated in the eggs pretreated with jasplakinolide or phalloidin. In addition, the sperm interacting with the eggs pretreated with actin drugs often generated multiple Ca(2+) waves, but tended to fail to enter the egg. Thus, our results indicated that generation of massive Ca(2+) waves is neither indicative of sperm entry nor sufficient for cortical granules exocytosis in the inseminated sea urchin eggs, whereas the structure and functionality of the actin cytoskeleton are the major determining factors in the two processes.

  4. The actin-binding protein Lasp promotes Oskar accumulation at the posterior pole of the Drosophila embryo.

    PubMed

    Suyama, Ritsuko; Jenny, Andreas; Curado, Silvia; Pellis-van Berkel, Wendy; Ephrussi, Anne

    2009-01-01

    During Drosophila oogenesis, Oskar mRNA is transported to the posterior pole of the oocyte, where it is locally translated and induces germ-plasm assembly. Oskar protein recruits all of the components necessary for the establishment of posterior embryonic structures and of the germline. Tight localization of Oskar is essential, as its ectopic expression causes severe patterning defects. Here, we show that the Drosophila homolog of mammalian Lasp1 protein, an actin-binding protein previously implicated in cell migration in vertebrate cell culture, contributes to the accumulation of Oskar protein at the posterior pole of the embryo. The reduced number of primordial germ cells in embryos derived from lasp mutant females can be rescued only with a form of Lasp that is capable of interacting with Oskar, revealing the physiological importance of the Lasp-Oskar interaction.

  5. [Molecular mechanisms for collective cell migration--perspectives and approaches from the studies on the actin-binding protein Girdin].

    PubMed

    Enomoto, Atsushi; Kato, Takuya; Asai, Naoya; Takahashi, Masahide

    2016-03-01

    In embryonal development and pathogenesis of diseases, cells often get connected and form small groups to undergo "collective migration", rather than spread out individually. The examples include the migration of neural crest cells and neuroblasts during development and the invasion of cancers in surrounding stroma, indicating the importance and significance of collective behavior of cells in the body. Recent studies have revealed the mechanisms for collective cell migration, which had seemed not to be the subject of traditional cell biology on single cells in culture. The heterogeneity in cell groups is also a key in understanding the mechanisms for collective cell migration. In this article, we describe recently emerging mechanisms for collective cell migration, with a particular focus on our studies on the actin-binding protein Girdin and tripartite motif containing 27. PMID:27025099

  6. F-actin binding regions on the androgen receptor and huntingtin increase aggregation and alter aggregate characteristics.

    PubMed

    Angeli, Suzanne; Shao, Jieya; Diamond, Marc I

    2010-01-01

    Protein aggregation is associated with neurodegeneration. Polyglutamine expansion diseases such as spinobulbar muscular atrophy and Huntington disease feature proteins that are destabilized by an expanded polyglutamine tract in their N-termini. It has previously been reported that intracellular aggregation of these target proteins, the androgen receptor (AR) and huntingtin (Htt), is modulated by actin-regulatory pathways. Sequences that flank the polyglutamine tract of AR and Htt might influence protein aggregation and toxicity through protein-protein interactions, but this has not been studied in detail. Here we have evaluated an N-terminal 127 amino acid fragment of AR and Htt exon 1. The first 50 amino acids of ARN127 and the first 14 amino acids of Htt exon 1 mediate binding to filamentous actin in vitro. Deletion of these actin-binding regions renders the polyglutamine-expanded forms of ARN127 and Htt exon 1 less aggregation-prone, and increases the SDS-solubility of aggregates that do form. These regions thus appear to alter the aggregation frequency and type of polyglutamine-induced aggregation. These findings highlight the importance of flanking sequences in determining the propensity of unstable proteins to misfold. PMID:20140226

  7. The N-terminal tropomyosin- and actin-binding sites are important for leiomodin 2’s function

    PubMed Central

    Ly, Thu; Moroz, Natalia; Pappas, Christopher T.; Novak, Stefanie M.; Tolkatchev, Dmitri; Wooldridge, Dayton; Mayfield, Rachel M.; Helms, Gregory; Gregorio, Carol C.; Kostyukova, Alla S.

    2016-01-01

    Leiomodin is a potent actin nucleator related to tropomodulin, a capping protein localized at the pointed end of the thin filaments. Mutations in leiomodin-3 are associated with lethal nemaline myopathy in humans, and leiomodin-2–knockout mice present with dilated cardiomyopathy. The arrangement of the N-terminal actin- and tropomyosin-binding sites in leiomodin is contradictory and functionally not well understood. Using one-dimensional nuclear magnetic resonance and the pointed-end actin polymerization assay, we find that leiomodin-2, a major cardiac isoform, has an N-terminal actin-binding site located within residues 43–90. Moreover, for the first time, we obtain evidence that there are additional interactions with actin within residues 124–201. Here we establish that leiomodin interacts with only one tropomyosin molecule, and this is the only site of interaction between leiomodin and tropomyosin. Introduction of mutations in both actin- and tropomyosin-binding sites of leiomodin affected its localization at the pointed ends of the thin filaments in cardiomyocytes. On the basis of our new findings, we propose a model in which leiomodin regulates actin poly­merization dynamics in myocytes by acting as a leaky cap at thin filament pointed ends. PMID:27307584

  8. The N-terminal tropomyosin- and actin-binding sites are important for leiomodin 2's function.

    PubMed

    Ly, Thu; Moroz, Natalia; Pappas, Christopher T; Novak, Stefanie M; Tolkatchev, Dmitri; Wooldridge, Dayton; Mayfield, Rachel M; Helms, Gregory; Gregorio, Carol C; Kostyukova, Alla S

    2016-08-15

    Leiomodin is a potent actin nucleator related to tropomodulin, a capping protein localized at the pointed end of the thin filaments. Mutations in leiomodin-3 are associated with lethal nemaline myopathy in humans, and leiomodin-2-knockout mice present with dilated cardiomyopathy. The arrangement of the N-terminal actin- and tropomyosin-binding sites in leiomodin is contradictory and functionally not well understood. Using one-dimensional nuclear magnetic resonance and the pointed-end actin polymerization assay, we find that leiomodin-2, a major cardiac isoform, has an N-terminal actin-binding site located within residues 43-90. Moreover, for the first time, we obtain evidence that there are additional interactions with actin within residues 124-201. Here we establish that leiomodin interacts with only one tropomyosin molecule, and this is the only site of interaction between leiomodin and tropomyosin. Introduction of mutations in both actin- and tropomyosin-binding sites of leiomodin affected its localization at the pointed ends of the thin filaments in cardiomyocytes. On the basis of our new findings, we propose a model in which leiomodin regulates actin poly-merization dynamics in myocytes by acting as a leaky cap at thin filament pointed ends.

  9. The N-terminal tropomyosin- and actin-binding sites are important for leiomodin 2's function.

    PubMed

    Ly, Thu; Moroz, Natalia; Pappas, Christopher T; Novak, Stefanie M; Tolkatchev, Dmitri; Wooldridge, Dayton; Mayfield, Rachel M; Helms, Gregory; Gregorio, Carol C; Kostyukova, Alla S

    2016-08-15

    Leiomodin is a potent actin nucleator related to tropomodulin, a capping protein localized at the pointed end of the thin filaments. Mutations in leiomodin-3 are associated with lethal nemaline myopathy in humans, and leiomodin-2-knockout mice present with dilated cardiomyopathy. The arrangement of the N-terminal actin- and tropomyosin-binding sites in leiomodin is contradictory and functionally not well understood. Using one-dimensional nuclear magnetic resonance and the pointed-end actin polymerization assay, we find that leiomodin-2, a major cardiac isoform, has an N-terminal actin-binding site located within residues 43-90. Moreover, for the first time, we obtain evidence that there are additional interactions with actin within residues 124-201. Here we establish that leiomodin interacts with only one tropomyosin molecule, and this is the only site of interaction between leiomodin and tropomyosin. Introduction of mutations in both actin- and tropomyosin-binding sites of leiomodin affected its localization at the pointed ends of the thin filaments in cardiomyocytes. On the basis of our new findings, we propose a model in which leiomodin regulates actin poly-merization dynamics in myocytes by acting as a leaky cap at thin filament pointed ends. PMID:27307584

  10. Utilization of paramagnetic relaxation enhancements for structural analysis of actin-binding proteins in complex with actin

    PubMed Central

    Huang, Shuxian; Umemoto, Ryo; Tamura, Yuki; Kofuku, Yutaka; Uyeda, Taro Q. P.; Nishida, Noritaka; Shimada, Ichio

    2016-01-01

    Actin cytoskeleton dynamics are controlled by various actin binding proteins (ABPs) that modulate the polymerization of the monomeric G-actin and the depolymerization of filamentous F-actin. Although revealing the structures of the actin/ABP complexes is crucial to understand how the ABPs regulate actin dynamics, the X-ray crystallography and cryoEM methods are inadequate to apply for the ABPs that interact with G- or F-actin with lower affinity or multiple binding modes. In this study, we aimed to establish the alternative method to build a structural model of G-actin/ABP complexes, utilizing the paramagnetic relaxation enhancement (PRE) experiments. Thymosin β4 (Tβ4) was used as a test case for validation, since its structure in complex with G-actin was reported recently. Recombinantly expressed G-actin, containing a cysteine mutation, was conjugated with a nitroxyl spin label at the specific site. Based on the intensity ratio of the 1H-15N HSQC spectra of Tβ4 in the complex with G-actin in the paramagnetic and diamagnetic states, the distances between the amide groups of Tβ4 and the spin label of G-actin were estimated. Using the PRE-derived distance constraints, we were able to compute a well-converged docking structure of the G-actin/Tβ4 complex that shows great accordance with the reference structure. PMID:27654858

  11. A membrane cytoskeleton from Dictyostelium discoideum. I. Identification and partial characterization of an actin-binding activity

    PubMed Central

    1981-01-01

    Dictyostelium discoideum plasma membranes isolated by each of three procedures bind F-actin. The interactions between these membranes and actin are examined by a novel application of falling ball viscometry. Treating the membranes as multivalent actin-binding particles analogous to divalent actin-gelation factors, we observe large increases in viscosity (actin cross-linking) when membranes of depleted actin and myosin are incubated with rabbit skeletal muscle F-actin. Pre- extraction of peripheral membrane proteins with chaotropes or the inclusion of Triton X-100 during the assay does not appreciably diminish this actin cross-linking activity. Lipid vesicles, heat- denatured membranes, proteolyzed membranes, or membranes containing endogenous actin show minimal actin cross-linking activity. Heat- denatured, but not proteolyzed, membranes regain activity when assayed in the presence of Triton X-100. Thus, integral membrane proteins appear to be responsible for some or all of the actin cross-linking activity of D. discoideum membranes. In the absence of MgATP, Triton X- 100 extraction of isolated D. discoideum membranes results in a Triton- insoluble residue composed of actin, myosin, and associated membrane proteins. The inclusion of MgATP before and during Triton extraction greatly diminishes the amount of protein in the Triton-insoluble residue without appreciably altering its composition. Our results suggest the existence of a protein complex stabilized by actin and/or myosin (membrane cytoskeleton) associated with the D. discoideum plasma membrane. PMID:6894148

  12. CP beta3, a novel isoform of an actin-binding protein, is a component of the cytoskeletal calyx of the mammalian sperm head.

    PubMed

    von Bülow, M; Rackwitz, H R; Zimbelmann, R; Franke, W W

    1997-05-25

    In the mammalian sperm head, the nucleus is tightly associated with the calyx, a cell type-specific cytoskeletal structure. Previously, we have identified and characterized some basic proteins such as calicin and cylicins I and II as major calyx components of bovine and human spermatids and spermatozoa. Surprisingly we have now discovered another calyx constituent which by amino acid sequencing and cDNA cloning was recognized as a novel isoform of the widespread beta subunit of the heterodimeric actin-binding "capping protein" (CP). This polypeptide, CP beta3, of sperm calices, is identical with the beta2 subunit present in diverse somatic cell types, except that it shows an amino-terminal extension of 29 amino acids and its mRNA is detected only in testis and, albeit in trace amounts, brain. This CP beta3 mRNA contains the additional sequence, encoded by exon 1 of the gene, which is missing in beta2 mRNAs. Antibodies specific for the beta3 amino-terminal addition have been used to identify the protein by immunoblotting and to localize it to the calyx structure by immunofluorescence microscopy. We conclude that in spermiogenesis the transcription of the gene encoding the beta1, beta2, and beta3 CP subunits is regulated specifically to include exon 1 and to give rise to the testis isoform CP beta3, which is integrated into the calyx structure of the forming sperm head. This surprising finding of an actin-binding protein isoform in an insoluble cytoskeletal structure is discussed in relation to the demonstrated roles of actin and certain actin-binding proteins, such as Limulus alpha-scruin, in spermiogenesis and spermatozoa.

  13. Actin-binding protein (ABP-280) filamin gene (FLN) maps telomeric to the color vision locus (R/GCP) and centromeric to G6PD in Xq28

    SciTech Connect

    Gorlin, J.B. Dana-Farber Cancer Institute, Boston, MA ); Henske, E.; Hartwig, J.H.; Kwiatkowski, D.J. ); Warren, S.T.; Kunst, C.B. ); D'Urso, M.; Palmieri, G. ); Bruns, G. )

    1993-08-01

    Actin-binding protein-280 (ABP-280) is a dimeric actin filament-crosslinking protein that promotes orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins. The authors have mapped the ABP-280 filamin gene (FLN) to Xq28 by Southern blot analysis of somatic cell hybrid lines, by fluorescence in situ hybridization, and through identification of portions of the FLN gene within cosmids and YACs mapped to Xq28. The FLN gene is found within a 200-kb region centromeric to the G6PD locus and telomeric to DSX52 and the color vision locus. 23 refs., 2 figs.

  14. Linking microfilaments to intracellular membranes: the actin-binding and vesicle-associated protein comitin exhibits a mannose-specific lectin activity.

    PubMed Central

    Jung, E; Fucini, P; Stewart, M; Noegel, A A; Schleicher, M

    1996-01-01

    Comitin is a 24 kDa actin-binding protein from Dictyostelium discoideum that is located primarily on Golgi and vesicle membranes. We have probed the molecular basis of comitin's interaction with both actin and membranes using a series of truncation mutants obtained by expressing the appropriate cDNA in Escherichia coli. Comitin dimerizes in solution; its principle actin-binding activity is located between residues 90 and 135. The N-terminal 135 'core' residues of comitin contain a 3-fold sequence repeat that is homologous to several monocotyledon lectins and which retains key residues that determine these lectins' three-dimensional structure and mannose binding. These repeats of comitin appear to mediate its interaction with mannose residues in glycoproteins or glycolipids on the cytoplasmic surface of membrane vesicles from D.discoideum, and comitin can be released from membranes with mannose. Our data indicate that comitin binds to vesicle membranes via mannose residues and, by way of its interaction with actin, links these membranes to the cytoskeleton. Images PMID:8635456

  15. αT-Catenin Is a Constitutive Actin-binding α-Catenin That Directly Couples the Cadherin·Catenin Complex to Actin Filaments*

    PubMed Central

    Wickline, Emily D.; Dale, Ian W.; Merkel, Chelsea D.; Heier, Jonathon A.; Stolz, Donna B.

    2016-01-01

    α-Catenin is the primary link between the cadherin·catenin complex and the actin cytoskeleton. Mammalian αE-catenin is allosterically regulated: the monomer binds the β-catenin·cadherin complex, whereas the homodimer does not bind β-catenin but interacts with F-actin. As part of the cadherin·catenin complex, αE-catenin requires force to bind F-actin strongly. It is not known whether these properties are conserved across the mammalian α-catenin family. Here we show that αT (testes)-catenin, a protein unique to amniotes that is expressed predominantly in the heart, is a constitutive actin-binding α-catenin. We demonstrate that αT-catenin is primarily a monomer in solution and that αT-catenin monomer binds F-actin in cosedimentation assays as strongly as αE-catenin homodimer. The β-catenin·αT-catenin heterocomplex also binds F-actin with high affinity unlike the β-catenin·αE-catenin complex, indicating that αT-catenin can directly link the cadherin·catenin complex to the actin cytoskeleton. Finally, we show that a mutation in αT-catenin linked to arrhythmogenic right ventricular cardiomyopathy, V94D, promotes homodimerization, blocks β-catenin binding, and in cardiomyocytes disrupts localization at cell-cell contacts. Together, our data demonstrate that αT-catenin is a constitutively active actin-binding protein that can physically couple the cadherin·catenin complex to F-actin in the absence of tension. We speculate that these properties are optimized to meet the demands of cardiomyocyte adhesion. PMID:27231342

  16. A novel function for the Hox gene Abd-B in the male accessory gland regulates the long-term female post-mating response in Drosophila.

    PubMed

    Gligorov, Dragan; Sitnik, Jessica L; Maeda, Robert K; Wolfner, Mariana F; Karch, François

    2013-03-01

    In insects, products of the male reproductive tract are essential for initiating and maintaining the female post-mating response (PMR). The PMR includes changes in egg laying, receptivity to courting males, and sperm storage. In Drosophila, previous studies have determined that the main cells of the male accessory gland produce some of the products required for these processes. However, nothing was known about the contribution of the gland's other secretory cell type, the secondary cells. In the course of investigating the late functions of the homeotic gene, Abdominal-B (Abd-B), we discovered that Abd-B is specifically expressed in the secondary cells of the Drosophila male accessory gland. Using an Abd-B BAC reporter coupled with a collection of genetic deletions, we discovered an enhancer from the iab-6 regulatory domain that is responsible for Abd-B expression in these cells and that apparently works independently from the segmentally regulated chromatin domains of the bithorax complex. Removal of this enhancer results in visible morphological defects in the secondary cells. We determined that mates of iab-6 mutant males show defects in long-term egg laying and suppression of receptivity, and that products of the secondary cells are influential during sperm competition. Many of these phenotypes seem to be caused by a defect in the storage and gradual release of sex peptide in female mates of iab-6 mutant males. We also found that Abd-B expression in the secondary cells contributes to glycosylation of at least three accessory gland proteins: ovulin (Acp26Aa), CG1656, and CG1652. Our results demonstrate that long-term post-mating changes observed in mated females are not solely induced by main cell secretions, as previously believed, but that secondary cells also play an important role in male fertility by extending the female PMR. Overall, these discoveries provide new insights into how these two cell types cooperate to produce and maintain a robust female PMR.

  17. Drosophila myosin-XX functions as an actin-binding protein to facilitate the interaction between Zyx102 and actin.

    PubMed

    Cao, Yang; White, Howard D; Li, Xiang-Dong

    2014-01-21

    The class XX myosin is a member of the diverse myosin superfamily and exists in insects and several lower invertebrates. DmMyo20, the class XX myosin in Drosophila, is encoded by dachs, which functions as a crucial downstream component of the Fat signaling pathway, influencing growth, affinity, and gene expression during development. Sequence analysis shows that DmMyo20 contains a unique N-terminal extension, the motor domain, followed by one IQ motif, and a C-terminal tail. To investigate the biochemical properties of DmMyo20, we expressed several DmMyo20 truncated constructs containing the motor domain in the baculovirus/Sf9 system. We found that the motor domain of DmMyo20 had neither ATPase activity nor the ability to bind to ATP, suggesting that DmMyo20 does not function as a molecular motor. We found that the motor domain of DmMyo20 could specifically bind to actin filaments in an ATP-independent manner and enhance the interaction between actin filaments and Zyx102, a downstream component of DmMyo20 in the Fat signaling pathway. These results suggest that DmMyo20 functions as a scaffold protein, but not as a molecular motor, in a signaling pathway controlling cell differentiation.

  18. Graduates and ABDs in Colleges of Education: Characteristics and Implications for the Structure of Doctoral Programs.

    ERIC Educational Resources Information Center

    1995

    This monograph is comprised of five papers originally presented at a symposium concerning degree completion or non-completion (ABDs--"all but dissertation") of doctoral students in colleges of education. The first paper is by Raymond Kluever and is titled "ABDs and Graduates from a College of Education: Responsibility, Barriers, and Facilitators."…

  19. Crystallization and X-ray diffraction of LGN in complex with the actin-binding protein afadin.

    PubMed

    Carminati, Manuel; Cecatiello, Valentina; Mapelli, Marina

    2016-02-01

    Asymmetric stem-cell divisions are fundamental for morphogenesis and tissue homeostasis. They rely on the coordination between cortical polarity and the orientation of the mitotic spindle, which is orchestrated by microtubule pulling motors recruited at the cortex by NuMA-LGN-Gαi complexes. LGN has emerged as a central component of the spindle-orientation pathway that is conserved throughout species. Its domain structure consists of an N-terminal TPR domain associating with NuMA, followed by four GoLoco motifs binding to Gαi subunits. The LGN(TPR) region is also involved in interactions with other membrane-associated proteins ensuring the correct cortical localization of microtubule motors, among which is the junctional protein afadin. To investigate the architecture of LGN(TPR) in complex with afadin, a chimeric fusion protein with a native linker derived from the region of afadin upstream of the LGN-binding domain was generated. The fusion protein behaves as a globular monomer in solution and readily crystallizes in the presence of sulfate-containing reservoirs. The crystals diffracted to 3.0 Å resolution and belonged to the cubic space group P213, with unit-cell parameter a = 170.3 Å. The structure of the engineered protein revealed that the crystal packing is promoted by the coordination of sulfate ions by residues of the afadin linker region and LGN(TPR).

  20. Abd-B expression in Porcellio scaber Latreille, 1804 (Isopoda: Crustacea): conserved pattern versus novel roles in development and evolution.

    PubMed

    Brena, C; Liu, P Z; Minelli, A; Kaufman, T C

    2005-01-01

    The Hox genes are intimately involved in patterning the animal body during development and are considered to have had a pivotal role in the evolution of different body plans among the metazoans. From this perspective, crustaceans, a group that has evolved an extreme diversity of body structures, represent a choice group in which to study the evolution of these genes and their expression. The expression of one of these genes, Abdominal-B (Abd-B), has only been studied in two distantly related crustaceans, Artemia and Sacculina, where it shows dissimilar patterns, highly differentiated from the one described in other arthropods. Moreover, we have no information for the Malacostraca. Thus, we cloned the gene Abd-B and followed its expression through development by in situ hybridization in the isopod Porcellio scaber. We found a highly dynamic expression pattern of PsAbd-B during embryonic development. In early stages, it is expressed in the posterior-most part of the germ band, in a domain common to several arthropods studied to date, and later it is expressed in the developing limb buds of the pleon and still later in the endopodites of the third to fifth pleopodites. This raises the interesting possibility of the involvement of this gene in the later respiratory specialization of these appendages. In association with the above expression domain, Abd-B appears to be expressed in later stages also in the ventral ectoderm, raising the further suggestion of its possible involvement in patterning the developing nervous system. Moreover, we show that the first pleopod and the endopodite of the second pleopod, whereas present as limb buds in early embryonic stages, are later reduced and actually absent in the first postembryonic stage, although they reappear again in adults. These appendages thus represent an example of Lazarus appendages. Our data show strong plasticity in the use of a key developmental gene and point out the necessity of further research that may end

  1. Abnormal actin binding of aberrant β-tropomyosins is a molecular cause of muscle weakness in TPM2-related nemaline and cap myopathy.

    PubMed

    Marttila, Minttu; Lemola, Elina; Wallefeld, William; Memo, Massimiliano; Donner, Kati; Laing, Nigel G; Marston, Steven; Grönholm, Mikaela; Wallgren-Pettersson, Carina

    2012-02-15

    NM (nemaline myopathy) is a rare genetic muscle disorder defined on the basis of muscle weakness and the presence of structural abnormalities in the muscle fibres, i.e. nemaline bodies. The related disorder cap myopathy is defined by cap-like structures located peripherally in the muscle fibres. Both disorders may be caused by mutations in the TPM2 gene encoding β-Tm (tropomyosin). Tm controls muscle contraction by inhibiting actin-myosin interaction in a calcium-sensitive manner. In the present study, we have investigated the pathogenetic mechanisms underlying five disease-causing mutations in Tm. We show that four of the mutations cause changes in affinity for actin, which may cause muscle weakness in these patients, whereas two show defective Ca2+ activation of contractility. We have also mapped the amino acids altered by the mutation to regions important for actin binding and note that two of the mutations cause altered protein conformation, which could account for impaired actin affinity. PMID:22084935

  2. Microtubule-associated Protein 2c Reorganizes Both Microtubules and Microfilaments into Distinct Cytological Structures in an Actin-binding Protein-280–deficient Melanoma Cell Line

    PubMed Central

    Cunningham, C. Casey; Leclerc, Nicole; Flanagan, Lisa A.; Lu, Mei; Janmey, Paul A.; Kosik, Kenneth S.

    1997-01-01

    The emergence of processes from cells often involves interactions between microtubules and microfilaments. Interactions between these two cytoskeletal systems are particularly apparent in neuronal growth cones. The juvenile isoform of the neuronal microtubule-associated protein 2 (MAP2c) is present in growth cones, where we hypothesize it mediates interactions between microfilaments and microtubules. To approach this problem in vivo, we used the human melanoma cell, M2, which lacks actin-binding protein-280 (ABP-280) and forms membrane blebs, which are not seen in wild-type or ABP-transfected cells. The microinjection of tau or mature MAP2 rescued the blebbing phenotype; MAP2c not only caused cessation of blebbing but also induced the formation of two distinct cellular structures. These were actin-rich lamellae, which often included membrane ruffles, and microtubule-bearing processes. The lamellae collapsed after treatment with cytochalasin D, and the processes retracted after treatment with colchicine. MAP2c was immunocytochemically visualized in zones of the cell that were devoid of tubulin, such as regions within the lamellae and in association with membrane ruffles. In vitro rheometry confirmed that MAP2c is an efficient actin gelation protein capable of organizing actin filaments into an isotropic array at very low concentrations; tau and mature MAP2 do not share this rheologic property. These results suggest that MAP2c engages in functionally specific interactions not only with microtubules but also with microfilaments. PMID:9049250

  3. ABD56 causes osteoclast apoptosis by inhibiting the NF{kappa}B and ERK pathways

    SciTech Connect

    Idris, Aymen; Mrak, Emanuela; Greig, Iain; Guidobono, Francesca; Ralston, Stuart H.; Hof, Rob van 't

    2008-06-20

    We have previously shown that the biphenylcarboxylic acid butanediol ester (ABD56) inhibits osteoclast formation and activity in vitro and in vivo. However, the mechanism of action of this compound is unknown. ABD56 inhibited osteoclast formation and caused osteoclast apoptosis, but had no effects on osteoblasts or macrophages. As the NF{kappa}B and MAPK pathways are essential for osteoclast formation and survival, we studied the effects of ABD56 on these pathways. ABD56 caused phosphorylation of p38, JNK and nuclear translocation of c-jun in osteoclasts. ABD56-induced apoptosis was prevented by the caspase inhibitor zVAD-fmk but was not prevented by the p38- or JNK-inhibitors. ABD56 completely abolished RANKL-induced I{kappa}B and ERK1/2 phosphorylation. Increasing the amount of RANKL partially rescued ABD56-induced apoptosis, indicating that the apoptosis is most probably due to the inhibition of survival signals such as ERK and NF{kappa}B, rather than activation of the p38 or Jnk MAPK pathways.

  4. Development, validation and characterization of a novel mouse model of Adynamic Bone Disease (ABD).

    PubMed

    Ng, Adeline H; Willett, Thomas L; Alman, Benjamin A; Grynpas, Marc D

    2014-11-01

    The etiology of Adynamic Bone Disease (ABD) is poorly understood but the hallmark of ABD is a lack of bone turnover. ABD occurs in renal osteodystrophy (ROD) and is suspected to occur in elderly patients on long-term anti-resorptive therapy. A major clinical concern of ABD is diminished bone quality and an increased fracture risk. To our knowledge, experimental animal models for ABD other than ROD-ABD have not been developed or studied. The objectives of this study were to develop a mouse model of ABD without the complications of renal ablation, and to characterize changes in bone quality in ABD relative to controls. To re-create the adynamic bone condition, 4-month old female Col2.3Δtk mice were treated with ganciclovir to specifically ablate osteoblasts, and pamidronate was used to inhibit osteoclastic resorption. Four groups of animals were used to characterize bone quality in ABD: Normal bone controls, No Formation controls, No Resorption controls, and an Adynamic group. After a 6-week treatment period, the animals were sacrificed and the bones were harvested for analyses. Bone quality assessments were conducted using established techniques including bone histology, quantitative backscattered electron imaging (qBEI), dual energy X-ray absorptiometry (DXA), microcomputed tomography (microCT), and biomechanical testing. Histomorphometry confirmed osteoblast-related hallmarks of ABD in our mouse model. Bone formation was near complete suppression in the No Formation and Adynamic specimens. Inhibition of bone resorption in the Adynamic group was confirmed by tartrate-resistant acid phosphatase (TRAP) stain. Normal bone mineral density and architecture were maintained in the Adynamic group, whereas the No Formation group showed a reduction in bone mineral content and trabecular thickness relative to the Adynamic group. As expected, the No Formation group had a more hypomineralized profile and the Adynamic group had a higher mean mineralization profile that is

  5. Development, validation and characterization of a novel mouse model of Adynamic Bone Disease (ABD).

    PubMed

    Ng, Adeline H; Willett, Thomas L; Alman, Benjamin A; Grynpas, Marc D

    2014-11-01

    The etiology of Adynamic Bone Disease (ABD) is poorly understood but the hallmark of ABD is a lack of bone turnover. ABD occurs in renal osteodystrophy (ROD) and is suspected to occur in elderly patients on long-term anti-resorptive therapy. A major clinical concern of ABD is diminished bone quality and an increased fracture risk. To our knowledge, experimental animal models for ABD other than ROD-ABD have not been developed or studied. The objectives of this study were to develop a mouse model of ABD without the complications of renal ablation, and to characterize changes in bone quality in ABD relative to controls. To re-create the adynamic bone condition, 4-month old female Col2.3Δtk mice were treated with ganciclovir to specifically ablate osteoblasts, and pamidronate was used to inhibit osteoclastic resorption. Four groups of animals were used to characterize bone quality in ABD: Normal bone controls, No Formation controls, No Resorption controls, and an Adynamic group. After a 6-week treatment period, the animals were sacrificed and the bones were harvested for analyses. Bone quality assessments were conducted using established techniques including bone histology, quantitative backscattered electron imaging (qBEI), dual energy X-ray absorptiometry (DXA), microcomputed tomography (microCT), and biomechanical testing. Histomorphometry confirmed osteoblast-related hallmarks of ABD in our mouse model. Bone formation was near complete suppression in the No Formation and Adynamic specimens. Inhibition of bone resorption in the Adynamic group was confirmed by tartrate-resistant acid phosphatase (TRAP) stain. Normal bone mineral density and architecture were maintained in the Adynamic group, whereas the No Formation group showed a reduction in bone mineral content and trabecular thickness relative to the Adynamic group. As expected, the No Formation group had a more hypomineralized profile and the Adynamic group had a higher mean mineralization profile that is

  6. [Interacting insulators from the Drosophila melanogaster bithorax complex can form independent expression domains].

    PubMed

    Kyrchanova, O V; Ivleva, T A; Georgiev, P G

    2011-12-01

    Regulatory region of three bithorax complex genes, Ultrabithorax (Ubx), abdominal-A (abd-A), and Abdominal-B (Abd-B) can be divided into nine iab domains, capable of directing expression of one of the genes in certain abdominal parasegment of Drosophila. In the Abd-B regulatory region, three insulators were identified, including Fab-7 and Fab-8, which flanked the iab-7domain, and Mcp, which separated the Abd-B and abd-A regulatory regions. It was suggested that boundary insulators formed a barrier between active and repressed chromatin. In the present study, using the yellow and white reporter genes and different combinations of known insulators, Mcp, Fab-7, and Fab-8, it was demonstrated that only specific interaction of two insulators was capable of isolation of active and repressed chromatin, i.e., the formation of independent expression domains.

  7. The actin-binding proteins eps8 and gelsolin have complementary roles in regulating the growth and stability of mechanosensory hair bundles of mammalian cochlear outer hair cells.

    PubMed

    Olt, Jennifer; Mburu, Philomena; Johnson, Stuart L; Parker, Andy; Kuhn, Stephanie; Bowl, Mike; Marcotti, Walter; Brown, Steve D M

    2014-01-01

    Sound transduction depends upon mechanosensitive channels localized on the hair-like bundles that project from the apical surface of cochlear hair cells. Hair bundles show a stair-case structure composed of rows of stereocilia, and each stereocilium contains a core of tightly-packed and uniformly-polarized actin filaments. The growth and maintenance of the stereociliary actin core are dynamically regulated. Recently, it was shown that the actin-binding protein gelsolin is expressed in the stereocilia of outer hair cells (OHCs) and in its absence they become long and straggly. Gelsolin is part of a whirlin scaffolding protein complex at the stereocilia tip, which has been shown to interact with other actin regulatory molecules such as Eps8. Here we investigated the physiological effects associated with the absence of gelsolin and its possible overlapping role with Eps8. We found that, in contrast to Eps8, gelsolin does not affect mechanoelectrical transduction during immature stages of development. Moreover, OHCs from gelsolin knockout mice were able to mature into fully functional sensory receptors as judged by the normal resting membrane potential and basolateral membrane currents. Mechanoelectrical transducer current in gelsolin-Eps8 double knockout mice showed a profile similar to that observed in the single mutants for Eps8. We propose that gelsolin has a non-overlapping role with Eps8. While Eps8 is mainly involved in the initial growth of stereocilia in both inner hair cells (IHCs) and OHCs, gelsolin is required for the maintenance of mature hair bundles of low-frequency OHCs after the onset of hearing. PMID:24475274

  8. A Short Splice Form of Xin-Actin Binding Repeat Containing 2 (XIRP2) Lacking the Xin Repeats Is Required for Maintenance of Stereocilia Morphology and Hearing Function

    PubMed Central

    Francis, Shimon P.; Krey, Jocelyn F.; Krystofiak, Evan S.; Cui, Runjia; Nanda, Sonali; Xu, Wenhao; Kachar, Bechara; Barr-Gillespie, Peter G.

    2015-01-01

    Approximately one-third of known deafness genes encode proteins located in the hair bundle, the sensory hair cell's mechanoreceptive organelle. In previous studies, we used mass spectrometry to characterize the hair bundle's proteome, resulting in the discovery of novel bundle proteins. One such protein is Xin-actin binding repeat containing 2 (XIRP2), an actin-cross-linking protein previously reported to be specifically expressed in striated muscle. Because mutations in other actin-cross-linkers result in hearing loss, we investigated the role of XIRP2 in hearing function. In the inner ear, XIRP2 is specifically expressed in hair cells, colocalizing with actin-rich structures in bundles, the underlying cuticular plate, and the circumferential actin belt. Analysis using peptide mass spectrometry revealed that the bundle harbors a previously uncharacterized XIRP2 splice variant, suggesting XIRP2's role in the hair cell differs significantly from that reported in myocytes. To determine the role of XIRP2 in hearing, we applied clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9-mediated genome-editing technology to induce targeted mutations into the mouse Xirp2 gene, resulting in the elimination of XIRP2 protein expression in the inner ear. Functional analysis of hearing in the resulting Xirp2-null mice revealed high-frequency hearing loss, and ultrastructural scanning electron microscopy analyses of hair cells demonstrated stereocilia degeneration in these mice. We thus conclude that XIRP2 is required for long-term maintenance of hair cell stereocilia, and that its dysfunction causes hearing loss in the mouse. PMID:25653358

  9. Phosphatidylinositol 3-Kinase-Associated Protein (PI3KAP)/XB130 Crosslinks Actin Filaments through Its Actin Binding and Multimerization Properties In Vitro and Enhances Endocytosis in HEK293 Cells.

    PubMed

    Yamanaka, Daisuke; Akama, Takeshi; Chida, Kazuhiro; Minami, Shiro; Ito, Koichi; Hakuno, Fumihiko; Takahashi, Shin-Ichiro

    2016-01-01

    Actin-crosslinking proteins control actin filament networks and bundles and contribute to various cellular functions including regulation of cell migration, cell morphology, and endocytosis. Phosphatidylinositol 3-kinase-associated protein (PI3KAP)/XB130 has been reported to be localized to actin filaments (F-actin) and required for cell migration in thyroid carcinoma cells. Here, we show a role for PI3KAP/XB130 as an actin-crosslinking protein. First, we found that the carboxyl terminal region of PI3KAP/XB130 containing amino acid residues 830-840 was required and sufficient for localization to F-actin in NIH3T3 cells, and this region is directly bound to F-actin in vitro. Moreover, actin-crosslinking assay revealed that recombinant PI3KAP/XB130 crosslinked F-actin. In general, actin-crosslinking proteins often multimerize to assemble multiple actin-binding sites. We then investigated whether PI3KAP/XB130 could form a multimer. Blue native-PAGE analysis showed that recombinant PI3KAP/XB130 was detected at 250-1200 kDa although the molecular mass was approximately 125 kDa, suggesting that PI3KAP/XB130 formed multimers. Furthermore, we found that the amino terminal 40 amino acids were required for this multimerization by co-immunoprecipitation assay in HEK293T cells. Deletion mutants of PI3KAP/XB130 lacking the actin-binding region or the multimerizing region did not crosslink actin filaments, indicating that actin binding and multimerization of PI3KAP/XB130 were necessary to crosslink F-actin. Finally, we examined roles of PI3KAP/XB130 on endocytosis, an actin-related biological process. Overexpression of PI3KAP/XB130 enhanced dextran uptake in HEK 293 cells. However, most of the cells transfected with the deletion mutant lacking the actin-binding region incorporated dextran to a similar extent as control cells. Taken together, these results demonstrate that PI3KAP/XB130 crosslinks F-actin through both its actin-binding region and multimerizing region and plays

  10. Two distinct domains of protein 4.1 critical for assembly of functional nuclei in vitro.

    PubMed

    Krauss, Sharon Wald; Heald, Rebecca; Lee, Gloria; Nunomura, Wataru; Gimm, J Aura; Mohandas, Narla; Chasis, Joel Anne

    2002-11-15

    Protein 4.1R, a multifunctional structural protein, acts as an adaptor in mature red cell membrane skeletons linking spectrin-actin complexes to plasma membrane-associated proteins. In nucleated cells protein 4.1 is not associated exclusively with plasma membrane but is also detected at several important subcellular locations crucial for cell division. To identify 4.1 domains having critical functions in nuclear assembly, 4.1 domain peptides were added to Xenopus egg extract nuclear reconstitution reactions. Morphologically disorganized, replication deficient nuclei assembled when spectrin-actin-binding domain or NuMA-binding C-terminal domain peptides were present. However, control variant spectrin-actin-binding domain peptides incapable of binding actin or mutant C-terminal domain peptides with reduced NuMA binding had no deleterious effects on nuclear reconstitution. To test whether 4.1 is required for proper nuclear assembly, 4.1 isoforms were depleted with spectrin-actin binding or C-terminal domain-specific antibodies. Nuclei assembled in the depleted extracts were deranged. However, nuclear assembly could be rescued by the addition of recombinant 4.1R. Our data establish that protein 4.1 is essential for nuclear assembly and identify two distinct 4.1 domains, initially characterized in cytoskeletal interactions, that have crucial and versatile functions in nuclear assembly.

  11. Detection of nucleotide- and F-actin-induced movements in the switch II helix of the skeletal myosin using its differential oxidative cleavage mediated by an iron-EDTA complex disulfide-linked to the strong actin binding site.

    PubMed

    Bertrand, R; Capony, J P; Derancourt, J; Kassab, R

    1999-09-14

    We have synthesized the mixed disulfide, S-(2-nitro-5-thiobenzoic acid) cysteaminyl-EDTA, using a rapid procedure and water-soluble chemistry. Its disulfide-thiol exchange reaction with rabbit myosin subfragment-1 (S-1), analyzed by spectrophotometry, ATPase assays, and peptide mapping, led to the incorporation of the cysteaminyl-EDTA group into only Cys 540 on the heavy chain and into the unique cysteine on the alkali light chains. The former thiol, residing in the strong actin binding site, reacted at a much faster rate with a concomitant 3-fold decrease in the V(max) for acto-S-1 ATPase but without change in the essential enzymatic functions of S-1. Upon chelation of Fe(3+) ions to the Cys 540-bound EDTA and incubation of the S-1 derivative-Fe complex with ascorbic acid at pH 7.5, the 95 kDa heavy chain underwent a conformation-dependent, single-cut oxidative fragmentation within 5-15 A of Cys 540. Three pairs of fragments were formed which, after specific fluorescent labeling and SDS-PAGE, could be positioned along the heavy chain sequence as 68 kDa-26 kDa, 62 kDa-32 kDa, and 54 kDa-40 kDa. Densitometric measurements revealed that the yield of the 54 kDa-40 kDa pair of bands, but not that for the two other pairs, was very sensitive to S-1 binding to nucleotides or phosphate analogues as well as to F-actin. In binary complexes, all the former ligands specifically lowered the yield to 40% of S-1 alone, roughly in the following order: ADP = AMP-PNP > ATP = ADP.AlF(4) > ADP.BeF(x)() > PP(i). By contrast, rigor binding to F-actin increased the yield to 130%. In the ternary acto-S-1-ADP complex, the yield was again reduced to 80%, and it fell to 25% in acto-S-1-ADP.AlF(4), the putative transition state analogue complex of the acto-S-1 ATPase. These different quantitative changes reflect distinct ligand-induced conformations of the secondary structure element whose scission generates the 54 kDa-40 kDa species. According to the S-1 crystal structure, this element could

  12. Cholecystokinin (CCK) functional cholescintigraphy (FC) in patients suspected of acalculous biliary disease (ABD)

    SciTech Connect

    Fink-Bennett, D.; De Ridder, P.; Kolozsi, W.; Gordon, R.; Rapp, J.

    1984-01-01

    To determine if CCK FC can aid in the diagnosis (Dx.) of ABD, the authors retrospectively analyzed the max. gallbladder (GB) ejection fraction response (EFR) to CCK in 240 patients (pts.) with persistent symptoms of biliary colic, a normal GB Ultrasound exam and/or OCG. Each pt. (NPO after 12 A.M.) received 5 mCi of technetium (Tc)-99 Hepatolite. After max GB filling, .02 ..mu..g/kg CCK was administered (1-3 minutes) I.V. Background corrected GB EFs were determined q.5 min x4 by ratioing the pre-CCK GB cts. minus post-CCK GB cts. to pre-CCK GB cts. In 131/240 pts. the max. GBEFR was <35%; 76 had a cholecystectomy (Cx.), 2 an exploratory lap., 53 medical Rx. Of the 76 post-Cx. pts., 74 had chronic cholecystitis (CC) (67 acalculous, 7 calculous), 2 were normal. Exploratory lap. pts, had no GB disease. Clinically 69/70 (4 no followup, 1 no change) post-op CC pts. are improved. One normal GB pt. has persistent pain, the other a Sphincter of Oddi dyskinesia. Of the 53 medical Rx. pts. 23 are lost to followup, and 2 died. Twenty-four are clinically felt to have ABD, 4 are not. In 109/240 pts. the max GBEFR was >35%. Eleven underwent surgery, 98 medical Rx. 4/11 Cx. apts had CAC, 7 were normal. Of the 98 medical Rx. pts. 21 lack followup, 71 are clinically felt not to have ABD; 6 are felt to have ABD. CCK FC appears to be a useful test for the detection of ABD. Its predictive value (GBEF <35%) in Cx. pts. is 97%; in all pts. (assuming medical Rx. correct), 94% (sensitivity - 91%, specificity - 93%).

  13. UNC-45/CRO1/She4p (UCS) protein forms elongated dimer and joins two myosin heads near their actin binding region

    PubMed Central

    Shi, Hang; Blobel, Günter

    2010-01-01

    UNC-45/CRO1/She4p (UCS) proteins have variously been proposed to affect the folding, stability, and ATPase activity of myosins. They are the only proteins known to interact directly with the motor domain. To gain more insight into UCS function, we determined the atomic structure of the yeast UCS protein, She4p, at 2.9 Å resolution. We found that 16 helical repeats are organized into an L-shaped superhelix with an amphipathic N-terminal helix dangling off the short arm of the L-shaped molecule. In the crystal, She4p forms a 193-Å-long, zigzag-shaped dimer through three distinct and evolutionary conserved interfaces. We have identified She4p’s C-terminal region as a ligand for a 27-residue-long epitope on the myosin motor domain. Remarkably, this region consists of two adjacent, but distinct, binding epitopes localized at the nucleotide-responsive cleft between the nucleotide- and actin-filament-binding sites. One epitope is situated inside the cleft, the other outside the cleft. After ATP hydrolysis and Pi ejection, the cleft narrows at its base from 20 to 12 Å thereby occluding the inside the cleft epitope, while leaving the adjacent, outside the cleft binding epitope accessible to UCS binding. Hence, one cycle of higher and lower binding affinity would accompany one ATP hydrolysis cycle and a single step in the walk on an actin filament rope. We propose that a UCS dimer links two myosins at their motor domains and thereby functions as one of the determinants for step size of myosin on actin filaments. PMID:21115842

  14. The association of myosin IB with actin waves in dictyostelium requires both the plasma membrane-binding site and actin-binding region in the myosin tail.

    PubMed

    Brzeska, Hanna; Pridham, Kevin; Chery, Godefroy; Titus, Margaret A; Korn, Edward D

    2014-01-01

    F-actin structures and their distribution are important determinants of the dynamic shapes and functions of eukaryotic cells. Actin waves are F-actin formations that move along the ventral cell membrane driven by actin polymerization. Dictyostelium myosin IB is associated with actin waves but its role in the wave is unknown. Myosin IB is a monomeric, non-filamentous myosin with a globular head that binds to F-actin and has motor activity, and a non-helical tail comprising a basic region, a glycine-proline-glutamine-rich region and an SH3-domain. The basic region binds to acidic phospholipids in the plasma membrane through a short basic-hydrophobic site and the Gly-Pro-Gln region binds F-actin. In the current work we found that both the basic-hydrophobic site in the basic region and the Gly-Pro-Gln region of the tail are required for the association of myosin IB with actin waves. This is the first evidence that the Gly-Pro-Gln region is required for localization of myosin IB to a specific actin structure in situ. The head is not required for myosin IB association with actin waves but binding of the head to F-actin strengthens the association of myosin IB with waves and stabilizes waves. Neither the SH3-domain nor motor activity is required for association of myosin IB with actin waves. We conclude that myosin IB contributes to anchoring actin waves to the plasma membranes by binding of the basic-hydrophobic site to acidic phospholipids in the plasma membrane and binding of the Gly-Pro-Gln region to F-actin in the wave.

  15. Myosin Head Configuration in Relaxed Insect Flight Muscle: X-Ray Modeled Resting Cross-Bridges in a Pre-Powerstroke State Are Poised for Actin Binding

    PubMed Central

    AL-Khayat, Hind A.; Hudson, Liam; Reedy, Michael K.; Irving, Thomas C.; Squire, John M.

    2003-01-01

    Low-angle x-ray diffraction patterns from relaxed insect flight muscle recorded on the BioCAT beamline at the Argonne APS have been modeled to 6.5 nm resolution (R-factor 9.7%, 65 reflections) using the known myosin head atomic coordinates, a hinge between the motor (catalytic) domain and the light chain-binding (neck) region (lever arm), together with a simulated annealing procedure. The best head conformation angles around the hinge gave a head shape that was close to that typical of relaxed M•ADP•Pi heads, a head shape never before demonstrated in intact muscle. The best packing constrained the eight heads per crown within a compact crown shelf projecting at ∼90° to the filament axis. The two heads of each myosin molecule assume nonequivalent positions, one head projecting outward while the other curves round the thick filament surface to nose against the proximal neck of the projecting head of the neighboring molecule. The projecting heads immediately suggest a possible cross-bridge cycle. The relaxed projecting head, oriented almost as needed for actin attachment, will attach, then release Pi followed by ADP, as the lever arm with a purely axial change in tilt drives ∼10 nm of actin filament sliding on the way to the nucleotide-free limit of its working stroke. The overall arrangement appears well designed to support precision cycling for the myogenic oscillatory mode of contraction with its enhanced stretch-activation response used in flight by insects equipped with asynchronous fibrillar flight muscles. PMID:12885653

  16. Recent changes in climate, hydrology and sediment load in the Wadi Abd, Algeria (1970-2010)

    NASA Astrophysics Data System (ADS)

    Achite, Mohammed; Ouillon, Sylvain

    2016-04-01

    Here we investigate the changes of temperature, precipitation, river runoff and sediment transport in the Wadi Abd in northwest Algeria over a time series of 40 hydrological years (1970-2010). Temperature increased and precipitation decreased with the reduction in rainfall being relatively higher during the rainy season. A shift towards an earlier onset of first rains during summer was also found with cascading effects on hydrology (hydrological regimes, vegetation, etc.) and thus on erosion and sediment yield. During the 1980s, the flow regime shifted from perennial to intermittent with an amplification of the variations of discharge and a modification of the sediment regime with higher and more irregular suspended particulate flux. Sediment flux was shown to almost double every decade from the 1970s to the 2000s. The sediment regime shifted from two equivalent seasons of sediment yield (spring and fall) to a single major season regime. In the 2000s, autumn produced over 4 times more sediment than spring. The enhanced scatter of the C-Q pairs denotes an increase of hysteresis phenomena in the Wadi Abd that is probably related to the change in the hydrologic regime. At the end of the period, due to irregularity of the discharge, the ability of a rating curve to derive suspended sediment concentration from river discharge was poor.

  17. Modulation of food consumption and sleep-wake cycle in mice by the neutral CB1 antagonist ABD459.

    PubMed

    Goonawardena, Anushka V; Plano, Andrea; Robinson, Lianne; Ross, Ruth; Greig, Iain; Pertwee, Roger G; Hampson, Robert E; Platt, Bettina; Riedel, Gernot

    2015-04-01

    The brain endocannabinoid system is a potential target for the treatment of psychiatric and metabolic conditions. Here, a novel CB1 receptor antagonist (ABD459) was synthesized and assayed for pharmacological efficacy in vitro and for modulation of food consumption, vigilance staging and cortical electroencephalography in the mouse. ABD459 completely displaced the CB1 agonist CP99540 at a Ki of 8.6 nmol/l, and did not affect basal, but antagonized CP55940-induced GTPγS binding with a KB of 7.7 nmol/l. Acute ABD459 (3-20 mg/kg) reliably inhibited food consumption in nonfasted mice, without affecting motor activity. Active food seeking was reduced for 5-6 h postdrug, with no rebound after washout. Epidural recording of electroencephalogram confirmed that ABD459 (3 mg/kg) robustly reduced rapid eye movement (REM) sleep, with no alterations of wakefulness or non-REM sleep. Effects were strongest during 3 h postdrug, followed by a progressive washout period. The CB1 antagonist AM251 (3 mg/kg) and agonist WIN-55,212-2 (WIN-2: 3 mg/kg) also reduced REM, but variously affected other vigilance stages. WIN-2 caused a global suppression of normalized spectral power. AM251 and ABD459 lowered delta power and increased power in the theta band in the hippocampus, but not the prefrontal cortex. The neutral antagonist ABD459 thus showed a specific role of endocannabinoid release in attention and arousal, possibly through modulation of cholinergic activity.

  18. Modulation of food consumption and sleep–wake cycle in mice by the neutral CB1 antagonist ABD459

    PubMed Central

    Goonawardena, Anushka V.; Plano, Andrea; Robinson, Lianne; Ross, Ruth; Greig, Iain; Pertwee, Roger G.; Hampson, Robert E.; Platt, Bettina; Riedel, Gernot

    2015-01-01

    The brain endocannabinoid system is a potential target for the treatment of psychiatric and metabolic conditions. Here, a novel CB1 receptor antagonist (ABD459) was synthesized and assayed for pharmacological efficacy in vitro and for modulation of food consumption, vigilance staging and cortical electroencephalography in the mouse. ABD459 completely displaced the CB1 agonist CP99540 at a Ki of 8.6 nmol/l, and did not affect basal, but antagonized CP55940-induced GTPγS binding with a KB of 7.7 nmol/l. Acute ABD459 (3–20 mg/kg) reliably inhibited food consumption in nonfasted mice, without affecting motor activity. Active food seeking was reduced for 5–6 h postdrug, with no rebound after washout. Epidural recording of electroencephalogram confirmed that ABD459 (3 mg/kg) robustly reduced rapid eye movement (REM) sleep, with no alterations of wakefulness or non-REM sleep. Effects were strongest during 3 h postdrug, followed by a progressive washout period. The CB1 antagonist AM251 (3mg/kg) and agonist WIN-55,212-2 (WIN-2: 3 mg/kg) also reduced REM, but variously affected other vigilance stages. WIN-2 caused a global suppression of normalized spectral power. AM251 and ABD459 lowered delta power and increased power in the theta band in the hippocampus, but not the prefrontal cortex. The neutral antagonist ABD459 thus showed a specific role of endocannabinoid release in attention and arousal, possibly through modulation of cholinergic activity. PMID:25356730

  19. ABD1 is an Arabidopsis DCAF substrate receptor for CUL4-DDB1-based E3 ligases that acts as a negative regulator of abscisic acid signaling.

    PubMed

    Seo, Kyoung-In; Lee, Jae-Hoon; Nezames, Cynthia D; Zhong, Shangwei; Song, Eunyoung; Byun, Myung-Ok; Deng, Xing Wang

    2014-02-01

    Members of the DDB1-CUL4-associated factors (DCAFs) family directly bind to DAMAGED DNA BINDING PROTEIN1 (DDB1) and function as the substrate receptors in CULLIN4-based E3 (CUL4) ubiquitin ligases, which regulate the selective ubiquitination of proteins. Here, we describe a DCAF protein, ABD1 (for ABA-hypersensitive DCAF1), that negatively regulates abscisic acid (ABA) signaling in Arabidopsis thaliana. ABD1 interacts with DDB1 in vitro and in vivo, indicating that it likely functions as a CUL4 E3 ligase substrate receptor. ABD1 expression is induced by ABA, and mutations in ABD1 result in ABA- and NaCl-hypersensitive phenotypes. Loss of ABD1 leads to hyperinduction of ABA-responsive genes and higher accumulation of the ABA-responsive transcription factor ABA INSENSITIVE5 (ABI5), hypersensitivity to ABA during seed germination and seedling growth, enhanced stomatal closure, reduced water loss, and, ultimately, increased drought tolerance. ABD1 directly interacts with ABI5 in yeast two-hybrid assays and associates with ABI5 in vivo by coimmunoprecipitation, and the interaction was found in the nucleus by bimolecular fluorescence complementation. Furthermore, loss of ABD1 results in a retardation of ABI5 degradation by the 26S proteasome. Taken together, these data suggest that the DCAF-CUL4 E3 ubiquitin ligase assembled with ABD1 is a negative regulator of ABA responses by directly binding to and affecting the stability of ABI5 in the nucleus. PMID:24563203

  20. Direct binding of F actin to the cytoplasmic domain of the alpha 2 integrin chain in vitro

    NASA Technical Reports Server (NTRS)

    Kieffer, J. D.; Plopper, G.; Ingber, D. E.; Hartwig, J. H.; Kupper, T. S.

    1995-01-01

    The transmembrane integrins have been shown to interact with the cytoskeleton via noncovalent binding between cytoplasmic domains (CDs) of integrin beta chains and various actin binding proteins within the focal adhesion complex. Direct or indirect integrin alpha chain CD binding to the actin cytoskeleton has not been reported. We show here that actin, as an abundant constituent of focal adhesion complex proteins isolated from fibroblasts, binds strongly and specifically to alpha 2 CD, but not to alpha 1 CD peptide. Similar specific binding to alpha 2 CD peptide was seen for highly purified F actin, free of putative actin-binding proteins. The bound complex of actin and peptide was visualized directly by coprecipitation, and actin binding was abrogated by removal of a five amino acid sequence from the alpha 2 CD peptide. Our findings may explain the earlier observation that, while integrins alpha 2 beta 1 and alpha 1 beta 1 both bind to collagen, only alpha 2 beta 1 can mediate contraction of extracellular collagen matrices.

  1. 'Abd al-Rahman al-Sufi's 3-Step Magnitude System

    NASA Astrophysics Data System (ADS)

    Hafez, Ihsan; Stephenson, F. Richard; Orchiston, Wayne

    'Abd al-Rahmān al-ūfī's Book of the Fixed Stars dates from around AD 964 and is one of the most important medieval Arabic treatises on astronomy. In this paper we begin with a very brief introduction to the Book of the Fixed Stars. This book contains an extensive star catalogue that lists star coordinates and magnitude estimates for all of the Ptolemaic stars. However, in his book al-hūfī utilized three distinct intermediate magnitude values whereas Ptolemy only mentioned two. We believe that al-hūfī used what we have termed a '3-step intermediate magnitude system,' which is more accurate than Ptolemy's 2-step intermediate system. In this paper we examine in detail the accuracy of this unique 3-step system in comparison with Ptolemy's and modern magnitude values.

  2. Actin-binding protein regulation by microRNAs as a novel microbial strategy to modulate phagocytosis by host cells: the case of N-Wasp and miR-142-3p.

    PubMed

    Bettencourt, Paulo; Marion, Sabrina; Pires, David; Santos, Leonor F; Lastrucci, Claire; Carmo, Nuno; Blake, Jonathon; Benes, Vladimir; Griffiths, Gareth; Neyrolles, Olivier; Lugo-Villarino, Geanncarlo; Anes, Elsa

    2013-01-01

    Mycobacterium tuberculosis (Mtb) is a successful intracellular pathogen that thrives in macrophages (Mφs). There is a need to better understand how Mtb alters cellular processes like phagolysosome biogenesis, a classical determinant of its pathogenesis. A central feature of this bacteria's strategy is the manipulation of Mφ actin. Here, we examined the role of microRNAs (miRNAs) as a potential mechanism in the regulation of actin-mediated events leading to phagocytosis in the context of mycobacteria infection. Given that non-virulent Mycobacterium smegmatis also controls actin filament assembly to prolong its intracellular survival inside host cells, we performed a global transcriptomic analysis to assess the modulation of miRNAs upon M. smegmatis infection of the murine Mφ cell line, J774A.1. This approach identified miR-142-3p as a key candidate to be involved in the regulation of actin dynamics required in phagocytosis. We unequivocally demonstrate that miR-142-3p targets N-Wasp, an actin-binding protein required during microbial challenge. A gain-of-function approach for miR-142-3p revealed a down-regulation of N-Wasp expression accompanied by a decrease of mycobacteria intake, while a loss-of-function approach yielded the reciprocal increase of the phagocytosis process. Equally important, we show Mtb induces the early expression of miR-142-3p and partially down-regulates N-Wasp protein levels in both the murine J774A.1 cell line and primary human Mφs. As proof of principle, the partial siRNA-mediated knock down of N-Wasp resulted in a decrease of Mtb intake by human Mφs, reflected in lower levels of colony-forming units (CFU) counts over time. We therefore propose the modulation of miRNAs as a novel strategy in mycobacterial infection to control factors involved in actin filament assembly and other early events of phagolysosome biogenesis.

  3. Actin-binding protein regulation by microRNAs as a novel microbial strategy to modulate phagocytosis by host cells: the case of N-Wasp and miR-142-3p

    PubMed Central

    Bettencourt, Paulo; Marion, Sabrina; Pires, David; Santos, Leonor F.; Lastrucci, Claire; Carmo, Nuno; Blake, Jonathon; Benes, Vladimir; Griffiths, Gareth; Neyrolles, Olivier; Lugo-Villarino, Geanncarlo; Anes, Elsa

    2013-01-01

    Mycobacterium tuberculosis (Mtb) is a successful intracellular pathogen that thrives in macrophages (Mφs). There is a need to better understand how Mtb alters cellular processes like phagolysosome biogenesis, a classical determinant of its pathogenesis. A central feature of this bacteria's strategy is the manipulation of Mφ actin. Here, we examined the role of microRNAs (miRNAs) as a potential mechanism in the regulation of actin-mediated events leading to phagocytosis in the context of mycobacteria infection. Given that non-virulent Mycobacterium smegmatis also controls actin filament assembly to prolong its intracellular survival inside host cells, we performed a global transcriptomic analysis to assess the modulation of miRNAs upon M. smegmatis infection of the murine Mφ cell line, J774A.1. This approach identified miR-142-3p as a key candidate to be involved in the regulation of actin dynamics required in phagocytosis. We unequivocally demonstrate that miR-142-3p targets N-Wasp, an actin-binding protein required during microbial challenge. A gain-of-function approach for miR-142-3p revealed a down-regulation of N-Wasp expression accompanied by a decrease of mycobacteria intake, while a loss-of-function approach yielded the reciprocal increase of the phagocytosis process. Equally important, we show Mtb induces the early expression of miR-142-3p and partially down-regulates N-Wasp protein levels in both the murine J774A.1 cell line and primary human Mφs. As proof of principle, the partial siRNA-mediated knock down of N-Wasp resulted in a decrease of Mtb intake by human Mφs, reflected in lower levels of colony-forming units (CFU) counts over time. We therefore propose the modulation of miRNAs as a novel strategy in mycobacterial infection to control factors involved in actin filament assembly and other early events of phagolysosome biogenesis. PMID:23760605

  4. Deletion of the cytoplasmic domain of N-cadherin reduces, but does not eliminate, traction force-transmission.

    PubMed

    Lee, Eliot; Ewald, Makena L; Sedarous, Mary; Kim, Timothy; Weyers, Brent W; Truong, Rose Hong; Yamada, Soichiro

    2016-09-30

    Collective migration of epithelial cells is an integral part of embryonic development, wound healing, tissue renewal and carcinoma invasion. While previous studies have focused on cell-extracellular matrix adhesion as a site of migration-driving, traction force-transmission, cadherin mediated cell-cell adhesion is also capable of force-transmission. Using a soft elastomer coated with purified N-cadherin as a substrate and a Hepatocyte Growth Factor-treated, transformed MDCK epithelial cell line as a model system, we quantified traction transmitted by N-cadherin-mediated contacts. On a substrate coated with purified extracellular domain of N-cadherin, cell surface N-cadherin proteins arranged into puncta. N-cadherin mutants (either the cytoplasmic deletion or actin-binding domain chimera), however, failed to assemble into puncta, suggesting the assembly of focal adhesion like puncta requires the cytoplasmic domain of N-cadherin. Furthermore, the cytoplasmic domain deleted N-cadherin expressing cells exerted lower traction stress than the full-length or the actin binding domain chimeric N-cadherin. Our data demonstrate that N-cadherin junctions exert significant traction stress that requires the cytoplasmic domain of N-cadherin, but the loss of the cytoplasmic domain does not completely eliminate traction force transmission.

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

    PubMed

    Merabet, Samir; Litim-Mecheri, Isma; Karlsson, Daniel; Dixit, Richa; Saadaoui, Mehdi; Monier, Bruno; Brun, Christine; Thor, Stefan; Vijayraghavan, K; Perrin, Laurent; Pradel, Jacques; Graba, Yacine

    2011-10-01

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

  6. Fusion to an albumin-binding domain with a high affinity for albumin extends the circulatory half-life and enhances the in vivo antitumor effects of human TRAIL.

    PubMed

    Li, Rui; Yang, Hao; Jia, Dianlong; Nie, Qianxue; Cai, Huawei; Fan, Qing; Wan, Lin; Li, Lin; Lu, Xiaofeng

    2016-04-28

    Clinical applications of recombinant human tumor necrosis factor-related apoptosis-inducing ligand (hTRAIL) have been limited by their poor pharmacokinetics. Using endogenous albumin as a carrier is an attractive approach for circulatory half-life extension. Here, we produced ABD-hTRAIL and hTRAIL-ABD by fusing the albumin-binding domain (ABD) from protein G to the N- or C-terminus of hTRAIL. We found that ABD-hTRAIL bound human serum albumin (HSA) with a high affinity (0.4 ± 0.18 nM) and formed nanoparticles with an average diameter (~12 nm) above the threshold (~7 nm) of renal filtration. ABD-hTRAIL also bound mouse serum albumin (MSA); thus, its half-life was 40-50-fold greater than that of hTRAIL (14.1 ± 0.87 h vs 0.32 ± 0.14 h). Tumor uptake of ABD-hTRAIL 8-48 h post-injection was 6-16-fold that of hTRAIL. Consequently, the tumor suppression of ABD-hTRAIL in mice bearing subcutaneous xenografts was 3-4 times greater than that of hTRAIL. Additionally, the time period during which ABD-hTRAIL could kill circulating tumor cells was approximately 8 times longer than that of hTRAIL. These results demonstrate that ABD fused to the N-terminus endows hTRAIL with albumin binding ability; once it enters the vasculature, ABD mediates binding with endogenous albumin, thus prolonging the half-life and enhancing the antitumor effect of hTRAIL. However, hTRAIL-ABD did not show a high affinity for albumin and therefore did not display the prolonged circulatory half-life and enhanced antitumor effects. These results demonstrate that N-terminal, but not C-terminal, ABD-fusion is an efficient technique for enhancing the antitumor effects of hTRAIL by using endogenous albumin as a carrier.

  7. Crystal structure of the rigor-like human non-muscle myosin-2 motor domain.

    PubMed

    Münnich, Stefan; Pathan-Chhatbar, Salma; Manstein, Dietmar J

    2014-12-20

    We determined the crystal structure of the motor domain of human non-muscle myosin 2B (NM-2B) in a nucleotide-free state and at a resolution of 2.8 Å. The structure shows the motor domain with an open active site and the large cleft that divides the 50 kDa domain in a closed state. Compared to other rigor-like myosin motor domain structures, our structure shows subtle but significant conformational changes in regions important for actin binding and mechanochemical coupling. Moreover, our crystal structure helps to rationalize the impact of myosin, heavy chain 9 (MYH9)-related disease mutations Arg709Cys and Arg709His on the kinetic and functional properties of NM-2B and of the closely related non-muscle myosin 2A (NM-2A). PMID:25451231

  8. A GLP-1 receptor agonist conjugated to an albumin-binding domain for extended half-life.

    PubMed

    Lindgren, Joel; Refai, Essam; Zaitsev, Sergei V; Abrahmsén, Lars; Berggren, Per-Olof; Karlström, Amelie Eriksson

    2014-05-01

    Glucagon-like peptide 1 (GLP-1) and related peptide agonists have been extensively investigated for glycaemic control in Type 2 diabetes, and may also have therapeutic applications for other diseases. Due to the short half-life (t1/2  < 2 min) of the endogenous peptide, caused by proteolytic degradation and renal clearance, different strategies for half-life extension and sustained release have been explored. In the present study, conjugates between a GLP-1 analogue and a 5 kDa albumin-binding domain (ABD) derived from streptococcal protein G have been chemically synthesized and evaluated. ABD binds with high affinity to human serum albumin, which is highly abundant in plasma and functions as a drug carrier in the circulation. Three different GLP-1-ABD conjugates, with the two peptides connected by linkers of two, four, and six PEG units, respectively, were synthesized and tested in mouse pancreatic islets at high (11 mM) and low (3 mM) glucose concentration. Insulin release upon stimulation was shown to be glucose-dependent, showing no significant difference between the three different GLP-1-ABD conjugates and unconjugated GLP-1 analogue. The biological activity, in combination with the high affinity binding to albumin, make the GLP-1-ABD conjugates promising GLP-1 receptor agonists expected to show extended in vivo half-life.

  9. Crystallization and preliminary X-ray crystallographic analysis of the sclerostin-neutralizing Fab AbD09097.

    PubMed

    Boschert, Verena; Muth, Eva Maria; Knappik, Achim; Frisch, Christian; Mueller, Thomas D

    2015-04-01

    The secreted cystine-knot protein sclerostin was first identified from genetic screening of patients suffering from the rare bone-overgrowth diseases sclerosteosis and van Buchem disease. Sclerostin acts a negative regulator of bone growth through inhibiting the canonical Wnt signalling cascade by binding to and blocking the Wnt co-receptor LRP5/6. Its function in blocking osteoblastogenesis makes it an important target for osteoanabolic therapy approaches to treat osteoporosis, which is characterized by a progressive decrease in bone mass and density. In this work, the production, crystallization and preliminary X-ray diffraction data analysis of a sclerostin-neutralizing human Fab antibody fragment, AbD09097, obtained from a naive antibody library are reported. Crystals of the Fab AbD09097 belonged to space group P21, with unit-cell parameters a = 45.19, b = 78.49, c = 59.20 Å, β = 95.71° and diffracted X-rays to a resolution of 1.8 Å.

  10. A domain of synapsin I involved with actin bundling shares immunologic cross-reactivity with villin.

    PubMed

    Petrucci, T C; Mooseker, M S; Morrow, J S

    1988-01-01

    Synapsin I is a neuronal phosphoprotein that can bundle actin filaments in vitro. This activity is under phosphorylation control, and may be related to its putative in vivo role of regulating the clustering and release of small synaptic vesicles. We have compared human and bovine synapsin I by peptide mapping, and have used NTCB (2-nitro-5-thiocyano benzoic acid) cleavage to generate a series of peptide fragments from bovine synapsin I. After chymotryptic digestion, 88% of the tyrosine-containing fragments appear to be structurally identical in human and bovine synapsin I, as judged by their positions on high-resolution two-dimensional peptide maps. The alignment of the NTCB peptides within the parent protein have been determined by peptide mapping, and the ability of these fragments to precipitate with actin bundles has been measured. Only peptides that are derived from regions near the ends of the protein are active. One such 25-kDa peptide which sediments with actin also cross-reacts with antibodies to chicken villin, an actin binding and bundling protein derived from the intestinal microvillus. Since in other respects villin appears to be an unrelated protein, these results suggest the possibility that certain actin binding proteins may show immunologic cross-reactivity due to convergent evolution within the acting binding domain. PMID:3125185

  11. Characterization of the Enzymatic Activity of the Actin Cross-Linking Domain from the Vibrio cholerae MARTXVc Toxin

    PubMed Central

    Kudryashov, Dmitri S.; Cordero, Christina L.; Reisler, Emil; Fullner Satchell, Karla J.

    2008-01-01

    Vibrio cholerae is a Gram-negative bacterial pathogen that exports enterotoxins which alter host cells through a number of mechanisms resulting in diarrheal disease. Among the secreted toxins is the multifunctional, autoprocessing RTX toxin (MARTXVc), which disrupts actin cytoskeleton by covalently cross-linking actin monomers into oligomers. The region of the toxin responsible for cross-linking activity is the actin cross-linking domain (ACD). In this study, we demonstrate unambiguously that ACD utilizes G- and not F-actin as a substrate for the cross-linking reaction and hydrolyzes one molecule of ATP per cross-linking event. Furthermore, major actin binding proteins that regulate actin cytoskeleton in vivo do not block the cross-linking reaction in vitro. Cofilin inhibits the cross-linking of G- and F-actin at high mole ratio to actin, but accelerates F-actin cross-linking at low mole ratios. DNase I blocks completely the cross-linking of actin, likely due to steric hindrance with one of the cross-linking sites on actin. In the context of the holotoxin, the inhibition of Rho by the Rho-inactivating domain of MARTXVc (Sheahan, K.L., Satchell, K.J.F. 2007 Cellular Microbiology 9:1324-1335) would accelerate F-actin depolymerization and provide G-actin, alone or in complex with actin binding proteins, for cross-linking by ACD, ultimately leading to the observed rapid cell rounding. PMID:17951576

  12. 75 FR 26316 - In the Matter of the Designation of Qasim al-Rimi, Also Known as Qasim Yahya Mahda `abd al-Rimi...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-11

    ... published in the Federal Register. Dated: April 6, 2010. Hillary Rodham Clinton, Secretary of State... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF STATE In the Matter of the Designation of Qasim al-Rimi, Also Known as Qasim Yahya Mahda `abd al-Rimi, Also Known...

  13. Brush border myosin-I truncated in the motor domain impairs the distribution and the function of endocytic compartments in an hepatoma cell line.

    PubMed Central

    Durrbach, A; Collins, K; Matsudaira, P; Louvard, D; Coudrier, E

    1996-01-01

    Myosins I, a ubiquitous monomeric class of myosins that exhibits actin-based motor properties, are associated with plasma and/or vesicular membranes and have been suggested as players for trafficking events between cell surface and intracellular membranous structures. To investigate the function of myosins 1, we have transfected a mouse hepatoma cell line (BWTG3) with cDNAs encoding the chicken brush border myosin-I (BBMI) and two variants truncated in the motor domain. One variant is deleted of the first 446 amino acids and thereby lacks the ATP binding site, whereas the other is deleted of the entire motor domain and lacks the ATP and actin binding sites. We have observed (i) that significant amounts of the truncated variants are recovered with membrane fractions after cell fractionation, (ii) that they codistribute with a compartment containing alpha2-macroglobulin internalized for 30 min as determined by fluorescent microscopy, (iii) that the production of BBMI-truncated variants impairs the distribution of the acidic compartment and ligands internalized for 30 min, and (iv) that the production of the truncated variant containing the actin binding site decreases the rate of alpha2-macroglobulin degradation whereas the production of the variant lacking the ATP binding site and the actin binding site increases the rate of a2-macroglobulin degradation. These observations indicate that the two truncated variants have a dominant negative effect on the distribution and the function of the endocytic compartments. We propose that an unidentified myosin-I might contribute to the distribution of endocytic compartments in a juxtanuclear position and/or to the regulation of the delivery of ligands to the degradative compartment in BWTG3 cells. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:8692943

  14. Involvement of the cynABDS operon and the CO2-concentrating mechanism in the light-dependent transport and metabolism of cyanate by cyanobacteria.

    PubMed

    Espie, George S; Jalali, Farid; Tong, Tommy; Zacal, Natalie J; So, Anthony K-C

    2007-02-01

    The cyanobacteria Synechococcus elongatus strain PCC7942 and Synechococcus sp. strain UTEX625 decomposed exogenously supplied cyanate (NCO-) to CO2 and NH3 through the action of a cytosolic cyanase which required HCO3- as a second substrate. The ability to metabolize NCO- relied on three essential elements: proteins encoded by the cynABDS operon, the biophysical activity of the CO2-concentrating mechanism (CCM), and light. Inactivation of cynS, encoding cyanase, and cynA yielded mutants unable to decompose cyanate. Furthermore, loss of CynA, the periplasmic binding protein of a multicomponent ABC-type transporter, resulted in loss of active cyanate transport. Competition experiments revealed that native transport systems for CO2, HCO3-, NO3-, NO2-, Cl-, PO4(2-), and SO4(2-) did not contribute to the cellular flux of NCO- and that CynABD did not contribute to the flux of these nutrients, implicating CynABD as a novel primary active NCO- transporter. In the S. elongatus strain PCC7942 DeltachpX DeltachpY mutant that is defective in the full expression of the CCM, mass spectrometry revealed that the cellular rate of cyanate decomposition depended upon the size of the internal inorganic carbon (Ci) (HCO3- + CO2) pool. Unlike wild-type cells, the rate of NCO- decomposition by the DeltachpX DeltachpY mutant was severely depressed at low external Ci concentrations, indicating that the CCM was essential in providing HCO3- for cyanase under typical growth conditions. Light was required to activate and/or energize the active transport of both NCO- and Ci. Putative cynABDS operons were identified in the genomes of diverse Proteobacteria, suggesting that CynABDS-mediated cyanate metabolism is not restricted to cyanobacteria.

  15. Involvement of the cynABDS Operon and the CO2-Concentrating Mechanism in the Light-Dependent Transport and Metabolism of Cyanate by Cyanobacteria▿

    PubMed Central

    Espie, George S.; Jalali, Farid; Tong, Tommy; Zacal, Natalie J.; So, Anthony K.-C.

    2007-01-01

    The cyanobacteria Synechococcus elongatus strain PCC7942 and Synechococcus sp. strain UTEX625 decomposed exogenously supplied cyanate (NCO−) to CO2 and NH3 through the action of a cytosolic cyanase which required HCO3− as a second substrate. The ability to metabolize NCO− relied on three essential elements: proteins encoded by the cynABDS operon, the biophysical activity of the CO2-concentrating mechanism (CCM), and light. Inactivation of cynS, encoding cyanase, and cynA yielded mutants unable to decompose cyanate. Furthermore, loss of CynA, the periplasmic binding protein of a multicomponent ABC-type transporter, resulted in loss of active cyanate transport. Competition experiments revealed that native transport systems for CO2, HCO3−, NO3−, NO2−, Cl−, PO42−, and SO42− did not contribute to the cellular flux of NCO− and that CynABD did not contribute to the flux of these nutrients, implicating CynABD as a novel primary active NCO− transporter. In the S. elongatus strain PCC7942 ΔchpX ΔchpY mutant that is defective in the full expression of the CCM, mass spectrometry revealed that the cellular rate of cyanate decomposition depended upon the size of the internal inorganic carbon (Ci) (HCO3− + CO2) pool. Unlike wild-type cells, the rate of NCO− decomposition by the ΔchpX ΔchpY mutant was severely depressed at low external Ci concentrations, indicating that the CCM was essential in providing HCO3− for cyanase under typical growth conditions. Light was required to activate and/or energize the active transport of both NCO− and Ci. Putative cynABDS operons were identified in the genomes of diverse Proteobacteria, suggesting that CynABDS-mediated cyanate metabolism is not restricted to cyanobacteria. PMID:17122352

  16. Fusion of an albumin-binding domain extends the half-life of immunotoxins.

    PubMed

    Guo, Rui; Guo, Wenjun; Cao, Li; Liu, Hui; Liu, Jieyu; Xu, Hua; Huang, Weiqiang; Wang, Fengwei; Hong, Zhangyong

    2016-09-10

    Immunotoxins have documented potential as a cancer treatment due to their extreme potency; a single toxin molecule delivered to the cytosol may be sufficient to kill a cell. However, their short half-life in the circulatory system may be one of the key problems associated with the clinical use of immunotoxins and may continue to limit their therapeutic activity. Herein, we genetically fused an albumin-binding domain (ABD) to the human epidermal growth factor receptor 2 (HER2)-specific immunotoxin ZHER2-PE38 to extend the circulation time and thus improve the therapeutic outcome of this immunotoxin. Furthermore, the fusion of an ABD to the immunotoxin was found to promote non-covalent interactions between the immunotoxin and serum albumin, which rescue the immunotoxin from lysosomal degradation through a serum albumin-mediated interaction with the neonatal Fc receptor (FcRn). This manuscript reports the construction, purification, and characterization of the ABD-fused HER2-specific immunotoxin, ABD-ZHER2-PE38, both in vitro and in vivo. Compared with non-fused ZHER2-PE38, this new construct exhibits a clearly increased half-life in plasma (330.8 versus 13.5min, approximately 24.4-fold extension) and remarkably improved antitumor effects in an NCI-N87 subcutaneous xenograft model. Therefore, the new construct represents a potentially attractive therapeutic modality, and the proposed strategy may also have useful applications for current immunotoxin designs.

  17. Fusion of an albumin-binding domain extends the half-life of immunotoxins.

    PubMed

    Guo, Rui; Guo, Wenjun; Cao, Li; Liu, Hui; Liu, Jieyu; Xu, Hua; Huang, Weiqiang; Wang, Fengwei; Hong, Zhangyong

    2016-09-10

    Immunotoxins have documented potential as a cancer treatment due to their extreme potency; a single toxin molecule delivered to the cytosol may be sufficient to kill a cell. However, their short half-life in the circulatory system may be one of the key problems associated with the clinical use of immunotoxins and may continue to limit their therapeutic activity. Herein, we genetically fused an albumin-binding domain (ABD) to the human epidermal growth factor receptor 2 (HER2)-specific immunotoxin ZHER2-PE38 to extend the circulation time and thus improve the therapeutic outcome of this immunotoxin. Furthermore, the fusion of an ABD to the immunotoxin was found to promote non-covalent interactions between the immunotoxin and serum albumin, which rescue the immunotoxin from lysosomal degradation through a serum albumin-mediated interaction with the neonatal Fc receptor (FcRn). This manuscript reports the construction, purification, and characterization of the ABD-fused HER2-specific immunotoxin, ABD-ZHER2-PE38, both in vitro and in vivo. Compared with non-fused ZHER2-PE38, this new construct exhibits a clearly increased half-life in plasma (330.8 versus 13.5min, approximately 24.4-fold extension) and remarkably improved antitumor effects in an NCI-N87 subcutaneous xenograft model. Therefore, the new construct represents a potentially attractive therapeutic modality, and the proposed strategy may also have useful applications for current immunotoxin designs. PMID:27457423

  18. Novel Exenatide Analogs with Peptidic Albumin Binding Domains: Potent Anti-Diabetic Agents with Extended Duration of Action

    PubMed Central

    Levy, Odile E.; Jodka, Carolyn M.; Ren, Shijun Steven; Mamedova, Lala; Sharma, Abhinandini; Samant, Manoj; D’Souza, Lawrence J.; Soares, Christopher J.; Yuskin, Diane R.; Jin, Li Jenny; Parkes, David G.; Tatarkiewicz, Krystyna; Ghosh, Soumitra S.

    2014-01-01

    The design, synthesis and pharmacology of novel long-acting exenatide analogs for the treatment of metabolic diseases are described. These molecules display enhanced pharmacokinetic profile and potent glucoregulatory and weight lowering actions compared to native exenatide. [Leu14]exenatide-ABD is an 88 residue peptide amide incorporating an Albumin Binding Domain (ABD) scaffold. [Leu14]exenatide-ABP is a 53 residue peptide incorporating a short Albumin Binding Peptide (ABP). [Leu14]exenatide-ABD and [Leu14]exenatide-ABP exhibited nanomolar functional GLP-1 receptor potency and were metabolically stable in vitro in human plasma and in a pancreatic digestive enzyme mixture. Both molecules displayed picomolar and nanomolar binding association with albumin across multiple species and circulating half lives of 16 and 11 hours, respectively, post a single IV dose in rats. Unlike exenatide, both molecules elicited robust glucose lowering when injected 1 day prior to an oral glucose tolerance test, indicative of their extended duration of action. [Leu14]exenatide-ABD was compared to exenatide in a Lep ob/ob mouse model of diabetes. Twice-weekly subcutaneously dosed [Leu14]exenatide-ABD displayed superior glucose lowering and weight loss in diabetic mice when compared to continuously infused exenatide at the same total weekly dose. A single oral administration of each molecule via an enteric coated capsule to cynomolgus monkeys showed superior pharmacokinetics for [Leu14]exenatide-ABD as compared to [Leu14]exenatide-ABP with detectable exposure longer than 14 days. These studies support the potential use of these novel long acting exenatide analogs with different routes of administration for the treatment of type 2 diabetes. PMID:24503632

  19. Ezrin NH2-terminal domain inhibits the cell extension activity of the COOH-terminal domain

    PubMed Central

    1995-01-01

    Overexpression in insect cells of the full coding sequence of the human membrane cytoskeletal linker ezrin (1-586) was compared with that of a NH2-terminal domain (ezrin 1-233) and that of a COOH-terminal domain (ezrin 310-586). Ezrin (1-586), as well as ezrin (1-233) enhanced cell adhesion of infected Sf9 cells without inducing gross morphological changes in the cell structure. Ezrin (310-586) enhanced cell adhesion and elicited membrane spreading followed by microspike and lamellipodia extensions by mobilization of Sf9 cell actin. Moreover some microspikes elongated into thin processes, up to 200 microns in length, resembling neurite outgrowths by a mechanism requiring microtubule assembly. Kinetics of videomicroscopic and drug-interference studies demonstrated that mobilization of actin was required for tubulin assembly to proceed. A similar phenotype was observed in CHO cells when a comparable ezrin domain was transiently overexpressed. The shortest domain promoting cell extension was localized between residues 373-586. Removal of residues 566-586, involved in in vitro actin binding (Turunen, O., T. Wahlstrom, and A. Vaheri. 1994. J. Cell Biol. 126:1445- 1453), suppressed the extension activity. Coexpression of ezrin (1-233) with ezrin (310-586) in the same insect cells blocked the constitutive activity of ezrin COOH-terminal domain. The inhibitory activity was mapped within ezrin 115 first NH2-terminal residues. We conclude that ezrin has properties to promote cell adhesion, and that ezrin NH2- terminal domain negatively regulates membrane spreading and elongation properties of ezrin COOH-terminal domain. PMID:7896873

  20. Tectonic history and structural development of the Zallah-Dur al Abd Sub-basin, western Sirt Basin, Libya

    NASA Astrophysics Data System (ADS)

    Abdunaser, Khalifa M.; McCaffrey, Ken J. W.

    2015-04-01

    The Zallah-Dur al Abd Sub-basin area lies in the western part of the Sirt Basin of Libya. 2D seismic data covering an area of about 32,000 km² were studied along with the formation tops from 240 wells. We mapped a complex network of normal and probable strike-slip faults, generally striking NNW-SSE that control the asymmetry of the basin. Subordinate NE-SW structures acted as transverse faults controlling local depocentres that segment the Zallah-Dur al Abd Sub-basin. A number of active faults in the intra-basin area have been identified in seismic sections with generally moderate to high dip angles, and displaying evidence for positive and negative flower structures. The bordering extensional fault (the Gedari fault) passes at depth into a moderately SW-dipping structure crossing most of the Upper Mesozoic to Cenozoic stratigraphic section. Thickness variations adjacent to other major faults suggest also an original extensional system where inherited high-angle faults were reactivated throughout this time. A detailed analysis of the available seismic reflection and drill hole data shows that an obliquely rifted, multi-cyclic, NNW-SSE trending basin developed during the complex Upper Mesozoic Cenozoic rearrangement of Mediterranean tectonics. Multiple phases of rifting can be observed in the study area affecting a number of different horizons from Upper Cretaceous to Eocene. In the study area, the basin was initiated as a result of a Tethyan oblique extensional rift system that began in the Early Cretaceous and peaked in the Late Cretaceous. The basin reached its rift maturation phase during the Upper Cretaceous as a result of the continuing extensional tectonics on the marginal bounding NNW-SSE trending normal growth faults. During the Alpine-related tectonic pulses of Middle-Late Eocene the Sirt Basin underwent compression resulted in northward tilting of the basin, causing abrupt subsidence in the north and uplift on the basin southern shoulders, possibly

  1. Two protein 4.1 domains essential for mitotic spindle and aster microtubule dynamics and organization in vitro.

    PubMed

    Krauss, Sharon Wald; Lee, Gloria; Chasis, Joel Anne; Mohandas, Narla; Heald, Rebecca

    2004-06-25

    Multifunctional structural proteins belonging to the 4.1 family are components of nuclei, spindles, and centrosomes in vertebrate cells. Here we report that 4.1 is critical for spindle assembly and the formation of centrosome-nucleated and motor-dependent self-organized microtubule asters in metaphase-arrested Xenopus egg extracts. Immunodepletion of 4.1 disrupted microtubule arrays and mislocalized the spindle pole protein NuMA. Remarkably, assembly was completely rescued by supplementation with a recombinant 4.1R isoform. We identified two 4.1 domains critical for its function in microtubule polymerization and organization utilizing dominant negative peptides. The 4.1 spectrin-actin binding domain or NuMA binding C-terminal domain peptides caused morphologically disorganized structures. Control peptides with low homology or variant spectrin-actin binding domain peptides that were incapable of binding actin had no deleterious effects. Unexpectedly, the addition of C-terminal domain peptides with reduced NuMA binding caused severe microtubule destabilization in extracts, dramatically inhibiting aster and spindle assembly and also depolymerizing preformed structures. However, the mutant C-terminal peptides did not directly inhibit or destabilize microtubule polymerization from pure tubulin in a microtubule pelleting assay. Our data showing that 4.1 is a crucial factor for assembly and maintenance of mitotic spindles and self-organized and centrosome-nucleated microtubule asters indicates that 4.1 is involved in regulating both microtubule dynamics and organization. These investigations underscore an important functional context for protein 4.1 in microtubule morphogenesis and highlight a previously unappreciated role for 4.1 in cell division.

  2. The Investigation of Stars, Star Clusters and Nebulae in 'Abd al-Rahman-Sufi's Book of the Fixed Stars

    NASA Astrophysics Data System (ADS)

    Hafez, Ihsan; Stephenson, F. Richard; Orchiston, Wayne

    'Abd al-Rahān al-Sūfī (AD 903-986) is justly famous for his Book of the Fixed Stars. This is an outstanding Medieval treatise on astronomy that was written in AD 964. This work was developed from Ptolemy's Almagest, but was based upon al-Sūfī's own stellar observations. The Book of the Fixed Stars has been copied down through the ages, and currently 35 copies are known to exist in various archival repositories around the world. In this paper we begin with a brief introduction to the Book of the Fixed Stars and provide biographical material about al-Sūfī before reviewing his investigation of stars, star clusters, nebulae and galaxies in his book. We examine al-Sūfī's novel stellar magnitude system, his comments on star colours, and stars mentioned in his book but not in the Almagest. We conclude with a listing of star clusters, nebulae and galaxies, including the earliest-known mention of the Great Nebula in Andromeda.

  3. Observation of cytoskeleton dynamics in Arabidopsis-GFP-MAP4, -GFP-ABD2 plants under clinorotation

    NASA Astrophysics Data System (ADS)

    Shevchenko, Galina

    With the aim to investigate the impact of simulated microgravity on the cytoskeleton arrangement and plant cell growth we observed Arabidopsis thaliana transfected with GFP- MAP4 and GFP-ABD2 under clinorotation (2 rpm). This allowed us to visualize the tubulin microtubules and actin microfilaments in live cells and helped to follow the dynamics of cytoskeleton rearrangements in simulated microgravity. Ability to investigate the changes in live plant cells opens the wide perspectives for onboard research. We applied the pharmacological approach and investigated the behavior of microtubules when the microfilaments were disrupted and vice versa. Measurements of cell parameters in the distal elongation zone of plant root showed the slight discoordination of growth in cells with damaged actin microfilament. It is suggested that mutual structural interrelations of the cytoskeleton elements is essential for growth coordination in plant root. Clinorotation experiments revealed that root cell growth is less dependent upon the mutual co-alignment between the cytoskeleton elements. In this connection, we assume the involvement of cytoskeleton in the mechanism of growth restriction which is hidden under constant g-vector and is unmasked in simulated microgravity.

  4. The sclerostin-neutralizing antibody AbD09097 recognizes an epitope adjacent to sclerostin's binding site for the Wnt co-receptor LRP6.

    PubMed

    Boschert, V; Frisch, C; Back, J W; van Pee, K; Weidauer, S E; Muth, E-M; Schmieder, P; Beerbaum, M; Knappik, A; Timmerman, P; Mueller, T D

    2016-08-01

    The glycoprotein sclerostin has been identified as a negative regulator of bone growth. It exerts its function by interacting with the Wnt co-receptor LRP5/6, blocks the binding of Wnt factors and thereby inhibits Wnt signalling. Neutralizing anti-sclerostin antibodies are able to restore Wnt activity and enhance bone growth thereby presenting a new osteoanabolic therapy approach for diseases such as osteoporosis. We have generated various Fab antibodies against human and murine sclerostin using a phage display set-up. Biochemical analyses have identified one Fab developed against murine sclerostin, AbD09097 that efficiently neutralizes sclerostin's Wnt inhibitory activity. In vitro interaction analysis using sclerostin variants revealed that this neutralizing Fab binds to sclerostin's flexible second loop, which has been shown to harbour the LRP5/6 binding motif. Affinity maturation was then applied to AbD09097, providing a set of improved neutralizing Fab antibodies which particularly bind human sclerostin with enhanced affinity. Determining the crystal structure of AbD09097 provides first insights into how this antibody might recognize and neutralize sclerostin. Together with the structure-function relationship derived from affinity maturation these new data will foster the rational design of new and highly efficient anti-sclerostin antibodies for the therapy of bone loss diseases such as osteoporosis. PMID:27558933

  5. The sclerostin-neutralizing antibody AbD09097 recognizes an epitope adjacent to sclerostin's binding site for the Wnt co-receptor LRP6

    PubMed Central

    Boschert, V.; Frisch, C.; Back, J. W.; van Pee, K.; Weidauer, S. E.; Muth, E.-M.; Schmieder, P.; Beerbaum, M.; Knappik, A.; Timmerman, P.

    2016-01-01

    The glycoprotein sclerostin has been identified as a negative regulator of bone growth. It exerts its function by interacting with the Wnt co-receptor LRP5/6, blocks the binding of Wnt factors and thereby inhibits Wnt signalling. Neutralizing anti-sclerostin antibodies are able to restore Wnt activity and enhance bone growth thereby presenting a new osteoanabolic therapy approach for diseases such as osteoporosis. We have generated various Fab antibodies against human and murine sclerostin using a phage display set-up. Biochemical analyses have identified one Fab developed against murine sclerostin, AbD09097 that efficiently neutralizes sclerostin's Wnt inhibitory activity. In vitro interaction analysis using sclerostin variants revealed that this neutralizing Fab binds to sclerostin's flexible second loop, which has been shown to harbour the LRP5/6 binding motif. Affinity maturation was then applied to AbD09097, providing a set of improved neutralizing Fab antibodies which particularly bind human sclerostin with enhanced affinity. Determining the crystal structure of AbD09097 provides first insights into how this antibody might recognize and neutralize sclerostin. Together with the structure–function relationship derived from affinity maturation these new data will foster the rational design of new and highly efficient anti-sclerostin antibodies for the therapy of bone loss diseases such as osteoporosis. PMID:27558933

  6. Development of Recombinant Lactococcus lactis Displaying Albumin-Binding Domain Variants against Shiga Toxin 1 B Subunit.

    PubMed

    Zadravec, Petra; Marečková, Lucie; Petroková, Hana; Hodnik, Vesna; Perišić Nanut, Milica; Anderluh, Gregor; Štrukelj, Borut; Malý, Petr; Berlec, Aleš

    2016-01-01

    Infections with shiga toxin-producing bacteria, like enterohemorrhagic Escherichia coli and Shigella dysenteriae, represent a serious medical problem. No specific and effective treatment is available for patients with these infections, creating a need for the development of new therapies. Recombinant lactic acid bacterium Lactococcus lactis was engineered to bind Shiga toxin by displaying novel designed albumin binding domains (ABD) against Shiga toxin 1 B subunit (Stx1B) on their surface. Functional recombinant Stx1B was produced in Escherichia coli and used as a target for selection of 17 different ABD variants (named S1B) from the ABD scaffold-derived high-complex combinatorial library in combination with a five-round ribosome display. Two most promising S1Bs (S1B22 and S1B26) were characterized into more details by ELISA, surface plasmon resonance and microscale thermophoresis. Addition of S1Bs changed the subcellular distribution of Stx1B, completely eliminating it from Golgi apparatus most likely by interfering with its retrograde transport. All ABD variants were successfully displayed on the surface of L. lactis by fusing to the Usp45 secretion signal and to the peptidoglycan-binding C terminus of AcmA. Binding of Stx1B by engineered lactococcal cells was confirmed using flow cytometry and whole cell ELISA. Lactic acid bacteria prepared in this study are potentially useful for the removal of Shiga toxin from human intestine. PMID:27606705

  7. Development of Recombinant Lactococcus lactis Displaying Albumin-Binding Domain Variants against Shiga Toxin 1 B Subunit

    PubMed Central

    Zadravec, Petra; Marečková, Lucie; Petroková, Hana; Hodnik, Vesna; Perišić Nanut, Milica; Anderluh, Gregor; Štrukelj, Borut; Malý, Petr; Berlec, Aleš

    2016-01-01

    Infections with shiga toxin-producing bacteria, like enterohemorrhagic Escherichia coli and Shigella dysenteriae, represent a serious medical problem. No specific and effective treatment is available for patients with these infections, creating a need for the development of new therapies. Recombinant lactic acid bacterium Lactococcus lactis was engineered to bind Shiga toxin by displaying novel designed albumin binding domains (ABD) against Shiga toxin 1 B subunit (Stx1B) on their surface. Functional recombinant Stx1B was produced in Escherichia coli and used as a target for selection of 17 different ABD variants (named S1B) from the ABD scaffold-derived high-complex combinatorial library in combination with a five-round ribosome display. Two most promising S1Bs (S1B22 and S1B26) were characterized into more details by ELISA, surface plasmon resonance and microscale thermophoresis. Addition of S1Bs changed the subcellular distribution of Stx1B, completely eliminating it from Golgi apparatus most likely by interfering with its retrograde transport. All ABD variants were successfully displayed on the surface of L. lactis by fusing to the Usp45 secretion signal and to the peptidoglycan-binding C terminus of AcmA. Binding of Stx1B by engineered lactococcal cells was confirmed using flow cytometry and whole cell ELISA. Lactic acid bacteria prepared in this study are potentially useful for the removal of Shiga toxin from human intestine. PMID:27606705

  8. Cloning, overexpression, purification and crystallization of the CRN12 coiled-coil domain from Leishmania donovani

    PubMed Central

    Srivastava, Vijay Kumar; Rana, Ajay Kumar; Sahasrabuddhe, Amogh A.; Gupta, C. M; Pratap, J. V.

    2013-01-01

    Leishmania donovani coronin CRN12 is an actin-binding protein which consists of two domains: an N-terminal WD repeat domain and a C-terminal coiled-coil domain. The coiled-coil domain is 53 residues in length. Helix–helix interactions in general and coiled coils in particular are ubiquitous in the structure of proteins and play a significant role in the association among proteins, including supramolecular assemblies and transmembrane receptors that mediate cellular signalling, transport and actin dynamics. The L. donovani coronin CRN12 coiled-coil domain (5.8 kDa) was cloned, overexpressed, purified to homogeneity and the N-terminal 6×His tag was successfully removed by thrombin cleavage. Crystals of recombinant L. donovani coronin CRN12 coiled-coil domain were grown by vapour diffusion using a hanging-drop setup. Diffraction-quality crystals were obtained and data extending to 2.46 Å resolution were collected at 100 K on BM14, ESRF, Grenoble, France. The crystal belonged to the monoclinic space group C2, with unit-cell parameters a = 118.0, b = 50.6, c = 46.0 Å, β = 111.0°. Matthews coefficient (V M) calculations suggested the presence of 4–6 molecules in the asymmetric unit, corresponding to a solvent content of ∼33–55%, and are consistent with self-rotation function calculations. PMID:23695571

  9. Cloning, overexpression, purification and crystallization of the CRN12 coiled-coil domain from Leishmania donovani.

    PubMed

    Srivastava, Vijay Kumar; Rana, Ajay Kumar; Sahasrabuddhe, Amogh A; Gupta, C M; Pratap, J V

    2013-05-01

    Leishmania donovani coronin CRN12 is an actin-binding protein which consists of two domains: an N-terminal WD repeat domain and a C-terminal coiled-coil domain. The coiled-coil domain is 53 residues in length. Helix-helix interactions in general and coiled coils in particular are ubiquitous in the structure of proteins and play a significant role in the association among proteins, including supramolecular assemblies and transmembrane receptors that mediate cellular signalling, transport and actin dynamics. The L. donovani coronin CRN12 coiled-coil domain (5.8 kDa) was cloned, overexpressed, purified to homogeneity and the N-terminal 6×His tag was successfully removed by thrombin cleavage. Crystals of recombinant L. donovani coronin CRN12 coiled-coil domain were grown by vapour diffusion using a hanging-drop setup. Diffraction-quality crystals were obtained and data extending to 2.46 Å resolution were collected at 100 K on BM14, ESRF, Grenoble, France. The crystal belonged to the monoclinic space group C2, with unit-cell parameters a = 118.0, b = 50.6, c = 46.0 Å, β = 111.0°. Matthews coefficient (VM) calculations suggested the presence of 4-6 molecules in the asymmetric unit, corresponding to a solvent content of ∼33-55%, and are consistent with self-rotation function calculations. PMID:23695571

  10. Identification of sucrose synthase as an actin-binding protein

    NASA Technical Reports Server (NTRS)

    Winter, H.; Huber, J. L.; Huber, S. C.; Davies, E. (Principal Investigator)

    1998-01-01

    Several lines of evidence indicate that sucrose synthase (SuSy) binds both G- and F-actin: (i) presence of SuSy in the Triton X-100-insoluble fraction of microsomal membranes (i.e. crude cytoskeleton fraction); (ii) co-immunoprecipitation of actin with anti-SuSy monoclonal antibodies; (iii) association of SuSy with in situ phalloidin-stabilized F-actin filaments; and (iv) direct binding to F-actin, polymerized in vitro. Aldolase, well known to interact with F-actin, interfered with binding of SuSy, suggesting that a common or overlapping binding site may be involved. We postulate that some of the soluble SuSy in the cytosol may be associated with the actin cytoskeleton in vivo.

  11. Extending half-life by indirect targeting of the neonatal Fc receptor (FcRn) using a minimal albumin binding domain.

    PubMed

    Andersen, Jan Terje; Pehrson, Rikard; Tolmachev, Vladimir; Daba, Muluneh Bekele; Abrahmsén, Lars; Ekblad, Caroline

    2011-02-18

    The therapeutic and diagnostic efficiency of engineered small proteins, peptides, and chemical drug candidates is hampered by short in vivo serum half-life. Thus, strategies to tailor their biodistribution and serum persistence are highly needed. An attractive approach is to take advantage of the exceptionally long circulation half-life of serum albumin or IgG, which is attributed to a pH-dependent interaction with the neonatal Fc receptor (FcRn) rescuing these proteins from intracellular degradation. Here, we present molecular evidence that a minimal albumin binding domain (ABD) derived from streptococcal protein G can be used for efficient half-life extension by indirect targeting of FcRn. We show that ABD, and ABD recombinantly fused to an Affibody molecule, in complex with albumin does not interfere with the strictly pH-dependent FcRn-albumin binding kinetics. The same result was obtained in the presence of IgG. An in vivo study performed in rat confirmed that the clinically relevant human epidermal growth factor 2 (HER2)-targeting Affibody molecule fused to ABD has a similar half-life and biodistribution profile as serum albumin. The proof-of-concept described may be broadly applicable to extend the in vivo half-life of short lived biological or chemical drugs ultimately resulting in enhanced therapeutic or diagnostic efficiency, a more favorable dosing regimen, and improved patient compliance.

  12. Accommodation of structural rearrangements in the huntingtin-interacting protein 1 coiled-coil domain

    SciTech Connect

    Wilbur, Jeremy D.; Hwang, Peter K.; Brodsky, Frances M.; Fletterick, Robert J.

    2010-03-01

    Variable packing interaction related to the conformational flexibility within the huntingtin-interacting protein 1 coiled coil domain. Huntingtin-interacting protein 1 (HIP1) is an important link between the actin cytoskeleton and clathrin-mediated endocytosis machinery. HIP1 has also been implicated in the pathogenesis of Huntington’s disease. The binding of HIP1 to actin is regulated through an interaction with clathrin light chain. Clathrin light chain binds to a flexible coiled-coil domain in HIP1 and induces a compact state that is refractory to actin binding. To understand the mechanism of this conformational regulation, a high-resolution crystal structure of a stable fragment from the HIP1 coiled-coil domain was determined. The flexibility of the HIP1 coiled-coil region was evident from its variation from a previously determined structure of a similar region. A hydrogen-bond network and changes in coiled-coil monomer interaction suggest that the HIP1 coiled-coil domain is uniquely suited to allow conformational flexibility.

  13. Talin is required to position and expand the luminal domain of the Drosophila heart tube.

    PubMed

    Vanderploeg, Jessica; Jacobs, J Roger

    2015-09-15

    Fluid- and gas-transporting tubular organs are critical to metazoan development and homeostasis. Tubulogenesis involves cell polarization and morphogenesis to specify the luminal, adhesive, and basal cell domains and to establish an open lumen. We explore a requirement for Talin, a cytoplasmic integrin adapter, during Drosophila melanogaster embryonic heart tube development. Talin marks the presumptive luminal domain and is required to orient and develop an open luminal space within the heart. Genetic analysis demonstrates that loss of zygotic or maternal-and-zygotic Talin disrupts heart cell migratory dynamics, morphogenesis, and polarity. Talin is essential for subsequent polarization of luminal determinants Slit, Robo, and Dystroglycan as well as stabilization of extracellular and intracellular integrin adhesion factors. In the absence of Talin function, mini-lumens enriched in luminal factors form in ectopic locations. Rescue experiments performed with mutant Talin transgenes suggest that actin-binding is required for normal lumen formation, but not for initial heart cell polarization. We propose that Talin provides instructive cues to position the luminal domain and coordinate the actin cytoskeleton during Drosophila heart lumen development.

  14. A central role for the WH2 domain of Srv2/CAP in recharging actin monomers to drive actin turnover in vitro and in vivo

    PubMed Central

    Chaudhry, Faisal; Little, Kristin; Talarico, Lou; Quintero-Monzon, Omar; Goode, Bruce L.

    2010-01-01

    Cellular processes propelled by actin polymerization require rapid disassembly of filaments, and then efficient recycling of ADF/cofilin-bound ADP-actin monomers back to an assembly-competent ATP-bound state. How monomer recharging is regulated in vivo is still not well understood, but recent work suggests the involvement of the ubiquitous actin-monomer binding protein Srv2/CAP. To better understand Srv2/CAP mechanism, we explored the contribution of its WH2 domain, the function of which has remained highly elusive. We found that the WH2 domain binds to actin monomers and, unlike most other WH2 domains, exhibits similar binding affinity for ATP-actin and ADP-actin (Kd ~1.5μM). Mutations in the WH2 domain that impair actin binding disrupt the ability of purified full-length Srv2/CAP to catalyze nucleotide exchange on ADF/cofilin-bound actin monomers and accelerate actin turnover in vitro. The same mutations impair Srv2/CAP function in vivo in regulating actin organization, cell growth, and cell morphogenesis. Thus, normal cell growth and organization depend on the ability of Srv2/CAP to recharge actin monomers, and the WH2 domain plays a central role in this process. Our data also reveal that while most isolated WH2 domains inhibit nucleotide exchange on actin, WH2 domains in the context of intact proteins can help promote nucleotide exchange. PMID:20169536

  15. The Nucleocapsid Domain of Gag Is Dispensable for Actin Incorporation into HIV-1 and for Association of Viral Budding Sites with Cortical F-Actin

    PubMed Central

    Stauffer, Sarah; Rahman, Sheikh Abdul; de Marco, Alex; Carlson, Lars-Anders; Glass, Bärbel; Oberwinkler, Heike; Herold, Nikolas; Briggs, John A. G.; Müller, Barbara

    2014-01-01

    ABSTRACT Actin and actin-binding proteins are incorporated into HIV-1 particles, and F-actin has been suggested to bind the NC domain in HIV-1 Gag. Furthermore, F-actin has been frequently observed in the vicinity of HIV-1 budding sites by cryo-electron tomography (cET). Filamentous structures emanating from viral buds and suggested to correspond to actin filaments have been observed by atomic force microscopy. To determine whether the NC domain of Gag is required for actin association with viral buds and for actin incorporation into HIV-1, we performed comparative analyses of virus-like particles (VLPs) obtained by expression of wild-type HIV-1 Gag or a Gag variant where the entire NC domain had been replaced by a dimerizing leucine zipper [Gag(LZ)]. The latter protein yielded efficient production of VLPs with near-wild-type assembly kinetics and size and exhibited a regular immature Gag lattice. Typical HIV-1 budding sites were detected by using cET in cells expressing either Gag or Gag(LZ), and no difference was observed regarding the association of buds with the F-actin network. Furthermore, actin was equally incorporated into wild-type HIV-1 and Gag- or Gag(LZ)-derived VLPs, with less actin per particle observed than had been reported previously. Incorporation appeared to correlate with the relative intracellular actin concentration, suggesting an uptake of cytosol rather than a specific recruitment of actin. Thus, the NC domain in HIV-1 Gag does not appear to have a role in actin recruitment or actin incorporation into HIV-1 particles. IMPORTANCE HIV-1 particles bud from the plasma membrane, which is lined by a network of actin filaments. Actin was found to interact with the nucleocapsid domain of the viral structural protein Gag and is incorporated in significant amounts into HIV-1 particles, suggesting that it may play an active role in virus release. Using electron microscopy techniques, we previously observed bundles of actin filaments near HIV-1 buds

  16. Alfalfa yield response to inoculation with recombinant strains of Rhizobium meliloti with an extra copy of dctABD and/or modified nifA expression.

    PubMed

    Bosworth, A H; Williams, M K; Albrecht, K A; Kwiatkowski, R; Beynon, J; Hankinson, T R; Ronson, C W; Cannon, F; Wacek, T J; Triplett, E W

    1994-10-01

    The construction of rhizobial strains which increase plant biomass under controlled conditions has been previously reported. However, there is no evidence that these newly constructed strains increase legume yield under agricultural conditions. This work tested the hypothesis that carefully manipulating expression of additional copies of nifA and dctABD in strains of Rhizobium meliloti would increase alfalfa yield in the field. The rationale for this hypothesis is based on the positive regulatory role that nifA plays in the expression of the nif regulon and the fact that a supply of dicarboxylic acids from the plant is required as a carbon and energy source for nitrogen fixation by the Rhizobium bacteroids in the nodule. These recombinant strains, as well as the wild-type strains from which they were derived, are ideal tools to examine the effects of modifying or increasing the expression of these genes on alfalfa biomass. The experimental design comprised seven recombinant strains, two wild-type strains, and an uninoculated control. Each treatment was replicated eight times and was conducted at four field sites in Wisconsin. Recombinant strain RMBPC-2, which has an additional copy of both nifA and dctABD, increased alfalfa biomass by 12.9% compared with the yield with the wild-type strain RMBPC and 17.9% over that in the uninoculated control plot at the site where soil nitrogen and organic matter content was lowest. These increases were statistically significant at the 5% confidence interval for each of the three harvests made during the growing season. Strain RMBPC-2 did increase alfalfa biomass at the Hancock site; however, no other significant increases or decreases in alfalfa biomass were observed with the seven other recombinant strains at that site. At three sites where this experiment was conducted, either native rhizobial populations or soil nitrogen concentrations were high. At these sites, none of the recombinant strains affected yield. We conclude that

  17. Domain Engineering

    NASA Astrophysics Data System (ADS)

    Bjørner, Dines

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

  18. Murine genes related to the Drosophila AbdB homeotic genes are sequentially expressed during development of the posterior part of the body.

    PubMed Central

    Izpisúa-Belmonte, J C; Falkenstein, H; Dollé, P; Renucci, A; Duboule, D

    1991-01-01

    The cloning, characterization and developmental expression patterns of two novel murine Hox genes, Hox-4.6 and Hox-4.7, are reported. Structural data allow us to classify the four Hox-4 genes located in the most upstream (5') position in the HOX-4 complex as members of a large family of homeogenes related to the Drosophila homeotic gene Abdominal B (AbdB). It therefore appears that these vertebrate genes are derived from a selective amplification of an ancestral gene which gave rise, during evolution, to the most posterior of the insect homeotic genes so far described. In agreement with the structural colinearity, these genes have very posteriorly restricted expression profiles. In addition, their developmental expression is temporally regulated according to a cranio-caudal sequence which parallels the physical ordering of these genes along the chromosome. We discuss the phylogenetic alternative in the evolution of genetic complexity by amplifying either genes or regulatory sequences, as exemplified by this system in the mouse and Drosophila. Furthermore, the possible role of 'temporal colinearity' in the ontogeny of all coelomic (metamerized) metazoans showing a temporal anteroposterior morphogenetic progression is addressed. Images PMID:1676674

  19. The Cardiac Stress Response Factor Ms1 Can Bind to DNA and Has a Function in the Nucleus.

    PubMed

    Zaleska, Mariola; Fogl, Claudia; Kho, Ay Lin; Ababou, Abdessamad; Ehler, Elisabeth; Pfuhl, Mark

    2015-01-01

    Ms1 (also known as STARS and ABRA) has been shown to act as an early stress response gene in processes as different as hypertrophy in skeletal and cardiac muscle and growth of collateral blood vessels. It is important for cardiac development in zebrafish and is upregulated in mouse models for cardiac hypertrophy as well as in human failing hearts. Ms1 possesses actin binding sites at its C-terminus and is usually found in the cell bound to actin filaments in the cytosol or in sarcomeres. We determined the NMR structure of the only folded domain of Ms1 comprising the second actin binding site called actin binding domain 2 (ABD2, residues 294-375), and found that it is similar to the winged helix-turn-helix fold adopted mainly by DNA binding domains of transcriptional factors. In vitro experiments show specific binding of this domain, in combination with a newly discovered AT-hook motif located N-terminally, to the sequence (A/C/G)AAA(C/A). NMR and fluorescence titration experiments confirm that this motif is indeed bound specifically by the recognition helix. In neonatal rat cardiomyocytes endogenous Ms1 is found in the nucleus in a spotted pattern, reminiscent of PML bodies. In adult rat cardiomyocytes Ms1 is exclusively found in the sarcomere. A nuclear localisation site in the N-terminus of the protein is required for nuclear localisation. This suggests that Ms1 has the potential to act directly in the nucleus through specific interaction with DNA in development and potentially as a response to stress in adult tissues. PMID:26656831

  20. The Cardiac Stress Response Factor Ms1 Can Bind to DNA and Has a Function in the Nucleus

    PubMed Central

    Kho, Ay Lin; Ababou, Abdessamad; Ehler, Elisabeth; Pfuhl, Mark

    2015-01-01

    Ms1 (also known as STARS and ABRA) has been shown to act as an early stress response gene in processes as different as hypertrophy in skeletal and cardiac muscle and growth of collateral blood vessels. It is important for cardiac development in zebrafish and is upregulated in mouse models for cardiac hypertrophy as well as in human failing hearts. Ms1 possesses actin binding sites at its C-terminus and is usually found in the cell bound to actin filaments in the cytosol or in sarcomeres. We determined the NMR structure of the only folded domain of Ms1 comprising the second actin binding site called actin binding domain 2 (ABD2, residues 294–375), and found that it is similar to the winged helix-turn-helix fold adopted mainly by DNA binding domains of transcriptional factors. In vitro experiments show specific binding of this domain, in combination with a newly discovered AT-hook motif located N-terminally, to the sequence (A/C/G)AAA(C/A). NMR and fluorescence titration experiments confirm that this motif is indeed bound specifically by the recognition helix. In neonatal rat cardiomyocytes endogenous Ms1 is found in the nucleus in a spotted pattern, reminiscent of PML bodies. In adult rat cardiomyocytes Ms1 is exclusively found in the sarcomere. A nuclear localisation site in the N-terminus of the protein is required for nuclear localisation. This suggests that Ms1 has the potential to act directly in the nucleus through specific interaction with DNA in development and potentially as a response to stress in adult tissues. PMID:26656831

  1. Evidence for physical and functional interactions among two Saccharomyces cerevisiae SH3 domain proteins, an adenylyl cyclase-associated protein and the actin cytoskeleton.

    PubMed Central

    Lila, T; Drubin, D G

    1997-01-01

    In a variety of organisms, a number of proteins associated with the cortical actin cytoskeleton contain SH3 domains, suggesting that these domains may provide the physical basis for functional interactions among structural and regulatory proteins in the actin cytoskeleton. We present evidence that SH3 domains mediate at least two independent functions of the Saccharomyces cerevisiae actin-binding protein Abp1p in vivo. Abp1p contains a single SH3 domain that has recently been shown to bind in vitro to the adenylyl cyclase-associated protein Srv2p. Immunofluorescence analysis of Srv2p subcellular localization in strains carrying mutations in either ABP1 or SRV2 reveals that the Abp1p SH3 domain mediates the normal association of Srv2p with the cortical actin cytoskeleton. We also show that a site in Abp1p itself is specifically bound by the SH3 domain of the actin-associated protein Rvs167p. Genetic analysis provides evidence that Abp1p and Rvs167p have functions that are closely interrelated. Abp1 null mutations, like rvs167 mutations, result in defects in sporulation and reduced viability under certain suboptimal growth conditions. In addition, mutations in ABP1 and RVS167 yield similar profiles of genetic "synthetic lethal" interactions when combined with mutations in genes encoding other cytoskeletal components. Mutations which specifically disrupt the SH3 domain-mediated interaction between Abp1p and Srv2p, however, show none of the shared phenotypes of abp1 and rvs167 mutations. We conclude that the Abp1p SH3 domain mediates the association of Srv2p with the cortical actin cytoskeleton, and that Abp1p performs a distinct function that is likely to involve binding by the Rvs167p SH3 domain. Overall, work presented here illustrates how SH3 domains can integrate the activities of multiple actin cytoskeleton proteins in response to varying environmental conditions. Images PMID:9190214

  2. The nebulette repeat domain is necessary for proper maintenance of tropomyosin with the cardiac sarcomere.

    PubMed

    Bonzo, Jeremy R; Norris, Andrea A; Esham, Michael; Moncman, Carole L

    2008-11-15

    Nebulette is a cardiac-specific isoform of the giant actin-binding protein nebulin. Nebulette, having a mass of approximately 100 kDa, is only predicted to extend 150 nm from the edge of the Z-lines. Overexpression of the nebulette C-terminal linker and/or SH3 domains in chicken cardiomyocytes results in a loss of endogenous nebulette with a concomitant loss of tropomyosin (TPM) and troponin, as well as a shortening of the thin filaments. These data suggest that nebulette's position in the sarcomere is important for the maintenance of TPM, troponin and thin filament length. To evaluate this hypothesis, N-terminal nested truncations tagged with GFP were expressed in chicken cardiomyocytes and the cells were analyzed for the distribution of myofilament proteins. Minimal effects on the myofilaments were observed with N-terminal deletions of up to 10 modules; however, deletion of 15 modules replicated the phenotype observed with expression of the C-terminal fragments. Expression of internal deletions of nebulette verifies that a site between module 10 and 15 is important for TPM maintenance within the sarcomeric lattice. We have additionally isolated TPM cDNAs from a yeast two hybrid (Y2H) analysis. These data indicate the importance of the nebulette-TPM interactions in the maintenance and stability of the thin filaments.

  3. Structure and calcium-binding studies of calmodulin-like domain of human non-muscle α-actinin-1

    PubMed Central

    Drmota Prebil, Sara; Slapšak, Urška; Pavšič, Miha; Ilc, Gregor; Puž, Vid; de Almeida Ribeiro, Euripedes; Anrather, Dorothea; Hartl, Markus; Backman, Lars; Plavec, Janez; Lenarčič, Brigita; Djinović-Carugo, Kristina

    2016-01-01

    The activity of several cytosolic proteins critically depends on the concentration of calcium ions. One important intracellular calcium-sensing protein is α-actinin-1, the major actin crosslinking protein in focal adhesions and stress fibers. The actin crosslinking activity of α-actinin-1 has been proposed to be negatively regulated by calcium, but the underlying molecular mechanisms are poorly understood. To address this, we determined the first high-resolution NMR structure of its functional calmodulin-like domain (CaMD) in calcium-bound and calcium-free form. These structures reveal that in the absence of calcium, CaMD displays a conformationally flexible ensemble that undergoes a structural change upon calcium binding, leading to limited rotation of the N- and C-terminal lobes around the connecting linker and consequent stabilization of the calcium-loaded structure. Mutagenesis experiments, coupled with mass-spectrometry and isothermal calorimetry data designed to validate the calcium binding stoichiometry and binding site, showed that human non-muscle α-actinin-1 binds a single calcium ion within the N-terminal lobe. Finally, based on our structural data and analogy with other α-actinins, we provide a structural model of regulation of the actin crosslinking activity of α-actinin-1 where calcium induced structural stabilisation causes fastening of the juxtaposed actin binding domain, leading to impaired capacity to crosslink actin. PMID:27272015

  4. ['The spirit has left the bottle': the medieval Arabic physician 'Abd al-Latĭf ibn Yŭsuf al-Baghdădĭ: his medical work and his bizarre affiliation with twentieth-century spiritualism].

    PubMed

    Joosse, N Peter

    2007-01-01

    The Arabic physician 'Abd al-Latĭf ibn Yŭsuf al-Baghdădĭ, lived at the crossroads of the twelfth and the thirteenth century. His unbridled curiosity and his unquenchable thirst for knowledge of any kind brought him to far-away countries and regions and put him in contact with all sorts and conditions of people. The great Egyptian famine of the years 1200-1202 enabled him to study and examine thousands of human cadavers and skeletons at first hand. This led to a new understanding of the anatomical structure of the human body, and rejected the more or less antiquated ideas of the Greek doctor Galen of Pergamum. However, 'Abd al-Latĭf's vision was granted only a short life. After his death, his discovery sank into oblivion and as a consequence it was never again mentioned in Arabic medical manuals. From then on the Arabic physicians once more referred to the anatomical data which were developed and taught by Galen. Relatively few specimens of his remaining medical work were preserved for posterity. However, his Book of the two advices (or: K. al-Nasĭhatain) is of the utmost importance as a source for the medical thinking and the medical treatment in the late twelfth and the early thirteenth century A.D. During the years following World War I, 'Abd al-Latĭf's name reappeared within the spiritualistic movement in England. He became known as Abduhl Latif the great Persian physician and acted as a control of mediums. Until the late sixties, he practised the art of healing as the head of a medical mission somewhere in the Spheres. PMID:18447318

  5. Physician-anatomists of Italy in Şānīzāde Mehmed Atāullah Efendi's work Mir'āt al-abdān (Mirror of bodies).

    PubMed

    Aciduman, Ahmet; Arda, Berna

    2014-09-01

    Şānīzāde Mehmed Atāullah Efendi was a pioneer in the history of Turkish medical education with his work Ḫamse-i Şānīzāde (Five Works of Şānīzāde). The first of these works, Mir'āt al-abdān fī taşrīh-i a'ḍāi'l-insān (Mirror of the bodies in the dissection of the members of the human body), concerns anatomy and was written in 1816. Şānīzāde's Mir'āt al-abdān is an important milestone in the teaching of anatomy in the Ottoman Empire and was also the first book on anatomy both written in a modern manner and printed in the Ottoman Empire. This paper is based on investigation of a printed copy of Mir'āt al-Abdān in the library of the History of Medicine and Ethics Department, Ankara University Faculty of Medicine. The main text and explanations were transliterated into the contemporary Turkish alphabet. The names of European physicians and their eponyms in the main text and in the explanations of illustrations were identified and evaluated. The names of European masters of anatomy in Şānīzāde are mentioned either in the text or in plate explanations. These names and plates indicate well-known physicians and masters of anatomy whose works were examined and quoted by Şānīzāde. The references in Şānīzāde's book and presented in this study relate to Italian physician-anatomists such as Bartolomeo Eustachi, Gabriele Fallopio, Costanzo Varolio and to others, such as Andreas Vesalius and Adriaan van den Spiegel, who were also Padua-educated but not Italian. PMID:24753269

  6. Fusion to a highly stable consensus albumin binding domain allows for tunable pharmacokinetics.

    PubMed

    Jacobs, Steven A; Gibbs, Alan C; Conk, Michelle; Yi, Fang; Maguire, Diane; Kane, Colleen; O'Neil, Karyn T

    2015-10-01

    A number of classes of proteins have been engineered for high stability using consensus sequence design methods. Here we describe the engineering of a novel albumin binding domain (ABD) three-helix bundle protein. The resulting engineered ABD molecule, called ABDCon, is expressed at high levels in the soluble fraction of Escherichia coli and is highly stable, with a melting temperature of 81.5°C. ABDCon binds human, monkey and mouse serum albumins with affinity as high as 61 pM. The solution structure of ABDCon is consistent with the three-helix bundle design and epitope mapping studies enabled a precise definition of the albumin binding interface. Fusion of a 10 kDa scaffold protein to ABDCon results in a long terminal half-life of 60 h in mice and 182 h in cynomolgus monkeys. To explore the link between albumin affinity and in vivo exposure, mutations were designed at the albumin binding interface of ABDCon yielding variants that span an 11 000-fold range in affinity. The PK properties of five such variants were determined in mice in order to demonstrate the tunable nature of serum half-life, exposure and clearance with variations in albumin binding affinity.

  7. Recognition of lysine-rich peptide ligands by murine cortactin SH3 domain: CD, ITC, and NMR studies.

    PubMed

    Rubini, Chiara; Ruzza, Paolo; Spaller, Mark R; Siligardi, Giuliano; Hussain, Rohanah; Udugamasooriya, D Gomika; Bellanda, Massimo; Mammi, Stefano; Borgogno, Andrea; Calderan, Andrea; Cesaro, Luca; Brunati, Anna M; Donella-Deana, Arianna

    2010-01-01

    Cortactin is a ubiquitous actin-binding protein that regulates various aspects of cell dynamics and is implicated in the pathogenesis of human neoplasia. The sequence of cortactin contains a number of signaling motifs and an SH3 domain at the C-terminus, which mediates the interaction of the protein with several partners, including Shank2. A recombinant protein, comprising the murine cortactin SH3 domain fused to GST (GST-SH3(m-cort)), was prepared and used to assess the domain-binding affinity of potential peptide-ligands reproducing the proline-rich regions of human HPK1 and Shank2 proteins. The key residues involved in the SH3(m-cort) domain recognition were identified by three different approaches: non-immobilized ligand interaction assay by circular dichroism, isothermal titration calorimetry, and nuclear magnetic resonance. Our results show that the classical PxxPxK class II binding motif is not sufficient to mediate the interaction with GST-SH3(m-cort), an event that depends on the presence of additional basic residues located at either the N- or the C-terminus of the PxxPxK motif. Especially effective in promoting the peptide binding is a Lys residue at the -5 position, a determinant present in both P2 (HPK1 394-403) and S1 (Shank2 1168-1189) peptides. GST-SH3(m-cort) exhibits the highest affinity toward peptide S1, which contains additional Lys residues at the -3, -5, and -7 positions, indicating that the optimal consensus motif may be KPPxPxKxKxK. These results are supported by the in silico models of SH3(m-cort) complexed with P2 or S1, which highlight the domain residues that interact with the recognition determinants of the peptide-ligand and cooperate in binding stabilization.

  8. The EH-domain-containing protein Pan1 is required for normal organization of the actin cytoskeleton in Saccharomyces cerevisiae.

    PubMed Central

    Tang, H Y; Cai, M

    1996-01-01

    Normal cell growth and division in the yeast Saccharomyces cerevisiae involve dramatic and frequent changes in the organization of the actin cytoskeleton. Previous studies have suggested that the reorganization of the actin cytoskeleton in accordance with cell cycle progression is controlled, directly or indirectly, by the cyclin-dependent kinase Cdc28. Here we report that by isolating rapid-death mutants in the background of the Start-deficient cdc28-4 mutation, the essential yeast gene PAN1, previously thought to encode the yeast poly(A) nuclease, is identified as a new factor required for normal organization of the actin cytoskeleton. We show that at restrictive temperature, the pan1 mutant exhibited abnormal bud growth, failed to maintain a proper distribution of the actin cytoskeleton, was unable to reorganize actin the cytoskeleton during cell cycle, and was defective in cytokinesis. The mutant also displayed a random pattern of budding even at permissive temperature. Ectopic expression of PAN1 by the GAL promoter caused abnormal distribution of the actin cytoskeleton when a single-copy vector was used. Immunofluorescence staining revealed that the Pan1 protein colocalized with the cortical actin patches, suggesting that it may be a filamentous actin-binding protein. The Pan1 protein contains an EF-hand calcium-binding domain, a putative Src homology 3 (SH3)-binding domain, a region similar to the actin cytoskeleton assembly control protein Sla1, and two repeats of a newly identified protein motif known as the EH domain. These findings suggest that Pan1, recently recognized as not responsible for the poly(A) nuclease activity (A. B. Sachs and J. A. Deardorff, erratum, Cell 83:1059, 1995; R. Boeck, S. Tarun, Jr., M. Rieger, J. A. Deardorff, S. Muller-Auer, and A. B. Sachs, J. Biol. Chem. 271:432-438, 1996), plays an important role in the organization of the actin cytoskeleton in S. cerevisiae. PMID:8756649

  9. Systematic mutational analysis of the amino-terminal domain of the Listeria monocytogenes ActA protein reveals novel functions in actin-based motility.

    PubMed

    Lauer, P; Theriot, J A; Skoble, J; Welch, M D; Portnoy, D A

    2001-12-01

    The Listeria monocytogenes ActA protein acts as a scaffold to assemble and activate host cell actin cytoskeletal factors at the bacterial surface, resulting in directional actin polymerization and propulsion of the bacterium through the cytoplasm. We have constructed 20 clustered charged-to-alanine mutations in the NH2-terminal domain of ActA and replaced the endogenous actA gene with these molecular variants. These 20 clones were evaluated in several biological assays for phenotypes associated with particular amino acid changes. Additionally, each protein variant was purified and tested for stimulation of the Arp2/3 complex, and a subset was tested for actin monomer binding. These specific mutations refined the two regions involved in Arp2/3 activation and suggest that the actin-binding sequence of ActA spans 40 amino acids. We also identified a 'motility rate and cloud-to-tail transition' region in which nine contiguous mutations spanning amino acids 165-260 caused motility rate defects and changed the ratio of intracellular bacteria associated with actin clouds and comet tails without affecting Arp2/3 activation. Several unusual motility phenotypes were associated with amino acid changes in this region, including altered paths through the cytoplasm, discontinuous actin tails in host cells and the tendency to 'skid' or dramatically change direction while moving. These unusual phenotypes illustrate the complexity of ActA functions that control the actin-based motility of L. monocytogenes.

  10. Systematic mutational analysis of the amino-terminal domain of the Listeria monocytogenes ActA protein reveals novel functions in actin-based motility.

    PubMed

    Lauer, P; Theriot, J A; Skoble, J; Welch, M D; Portnoy, D A

    2001-12-01

    The Listeria monocytogenes ActA protein acts as a scaffold to assemble and activate host cell actin cytoskeletal factors at the bacterial surface, resulting in directional actin polymerization and propulsion of the bacterium through the cytoplasm. We have constructed 20 clustered charged-to-alanine mutations in the NH2-terminal domain of ActA and replaced the endogenous actA gene with these molecular variants. These 20 clones were evaluated in several biological assays for phenotypes associated with particular amino acid changes. Additionally, each protein variant was purified and tested for stimulation of the Arp2/3 complex, and a subset was tested for actin monomer binding. These specific mutations refined the two regions involved in Arp2/3 activation and suggest that the actin-binding sequence of ActA spans 40 amino acids. We also identified a 'motility rate and cloud-to-tail transition' region in which nine contiguous mutations spanning amino acids 165-260 caused motility rate defects and changed the ratio of intracellular bacteria associated with actin clouds and comet tails without affecting Arp2/3 activation. Several unusual motility phenotypes were associated with amino acid changes in this region, including altered paths through the cytoplasm, discontinuous actin tails in host cells and the tendency to 'skid' or dramatically change direction while moving. These unusual phenotypes illustrate the complexity of ActA functions that control the actin-based motility of L. monocytogenes. PMID:11886549

  11. Properties and catalytic activities of MICAL1, the flavoenzyme involved in cytoskeleton dynamics, and modulation by its CH, LIM and C-terminal domains.

    PubMed

    Vitali, Teresa; Maffioli, Elisa; Tedeschi, Gabriella; Vanoni, Maria A

    2016-03-01

    MICAL1 is a cytoplasmic 119 kDa protein participating in cytoskeleton dynamics through the NADPH-dependent oxidase and F-actin depolymerizing activities of its N-terminal flavoprotein domain, which is followed by calponin homology (CH), LIM domains and a C-terminal region with Pro-, Glu-rich and coiled-coil motifs. MICAL1 and truncated forms lacking the C-terminal, LIM and/or CH regions have been produced and characterized. The CH, LIM and C-terminal regions cause an increase of Km,NADPH exhibited by the NADPH oxidase activity of the flavoprotein domain, paralleling changes in the overall protein charge. The C-terminus also determines a ∼ 10-fold decrease of kcat, revealing its role in establishing an inactive/active conformational equilibrium, which is at the heart of the regulation of MICAL1 in cells. F-actin lowers Km,NADPH (10-50 μM) and increases kcat (10-25 s(-1)) to similar values for all MICAL forms. The apparent Km,actin of MICAL1 is ∼ 10-fold higher than that of the other forms (3-5 μM), reflecting the fact that F-actin binds to the flavoprotein domain in the MICAL's active conformation and stabilizes it. Analyses of the reaction in the presence of F-actin indicate that actin depolymerization is mediated by H2O2 produced by the NADPH oxidase reaction, rather than due to direct hydroxylation of actin methionine residues.

  12. Unconventional actins and actin-binding proteins in human protozoan parasites.

    PubMed

    Gupta, C M; Thiyagarajan, S; Sahasrabuddhe, A A

    2015-06-01

    Actin and its regulatory proteins play a key role in several essential cellular processes such as cell movement, intracellular trafficking and cytokinesis in most eukaryotes. While these proteins are highly conserved in higher eukaryotes, a number of unicellular eukaryotic organisms contain divergent forms of these proteins which have highly unusual biochemical and structural properties. Here, we review the biochemical and structural properties of these unconventional actins and their core binding proteins which are present in commonly occurring human protozoan parasites.

  13. Simiate is an Actin binding protein involved in filopodia dynamics and arborization of neurons

    PubMed Central

    Derlig, Kristin; Ehrhardt, Toni; Gießl, Andreas; Brandstätter, Johann H.; Enz, Ralf; Dahlhaus, Regina

    2014-01-01

    The Actin cytoskeleton constitutes the functional base for a multitude of cellular processes extending from motility and migration to cell mechanics and morphogenesis. The latter is particularly important to neuronal cells since the accurate functioning of the brain crucially depends on the correct arborization of neurons, a process that requires the formation of several dozens to hundreds of dendritic branches. Recently, a model was proposed where different transcription factors are detailed to distinct facets and phases of dendritogenesis and exert their function by acting on the Actin cytoskeleton, however, the proteins involved as well as the underlying molecular mechanisms are largely unknown. Here, we demonstrate that Simiate, a protein previously indicated to activate transcription, directly associates with both, G- and F-Actin and in doing so, affects Actin polymerization and Actin turnover in living cells. Imaging studies illustrate that Simiate particularly influences filopodia dynamics and specifically increases the branching of proximal, but not distal dendrites of developing neurons. The data suggests that Simiate functions as a direct molecular link between transcription regulation on one side, and dendritogenesis on the other, wherein Simiate serves to coordinate the development of proximal and distal dendrites by acting on the Actin cytoskeleton of filopodia and on transcription regulation, hence supporting the novel model. PMID:24782708

  14. Isolation of an actin-binding protein from membranes of Dictyostelium discoideum

    PubMed Central

    1985-01-01

    We prepared a probe of radiolabeled, glutaraldehyde cross-linked filamentous actin (F-actin) to study binding of actin to membranes of Dictyostelium discoideum. The probe bound to membranes or detergent extracts of membranes with a high affinity and in a saturable manner. The binding could be reduced by boiling of either the actin probe or the membranes, or by addition of excess native F-actin, but not by addition of an equivalent amount of bovine serum albumin, to the assay. The probe labeled several proteins when used to overlay sodium dodecyl sulfate gels of Dictyostelium membranes. One of these labeled proteins was a 24,000-mol-wt protein (p24), which was soluble only in the presence of a high concentration of sodium deoxycholate (5%, wt/vol) at room temperature or above. The p24 was purified by selective detergent extraction and column chromatography. When tested in a novel two-phase binding assay, p24 bound both native monomeric actin (G-actin) and F- actin in a specific manner. In this assay, G-actin bound p24 with a submicromolar affinity. PMID:3972891

  15. REM sleep deprivation attenuates actin-binding protein cortactin: a link between sleep and hippocampal plasticity.

    PubMed

    Davis, Christopher J; Meighan, Peter C; Taishi, Ping; Krueger, James M; Harding, Joseph W; Wright, John W

    2006-06-12

    Rapid eye-movement sleep (REMS) is thought to affect synaptic plasticity. Cortactin is a cytoskeletal protein critically involved in the regulation of actin branching and stabilization including the actin backbone of dendritic spines. Hippocampal cortactin levels, phosphorylation, and processing appear to be altered during learning and long-term potentiation (LTP); consistent with a role for cortactin in the dendritic restructuring that accompanies synaptic plasticity. In this study juvenile male Sprague-Dawley rats were selectively REMS-deprived (RD) for 48 h by the flowerpot method. Cage control (CC) and large pedestal control (PC) animals were used for comparison. Animals were euthanized immediately, or 12 h, after removal from the pedestal. The hippocampus was dissected, flash-frozen, and stored for subsequent Western blot or quantitative RT-PCR analysis of cortactin. Cortactin mRNA/cDNA levels initially rose in PC and RD rats but returned to CC levels by 12 h after removal from the pedestal. Predictably cortactin protein levels were initially unchanged but were up-regulated after 12 h. The PC group had more total and tyrosine-phosphorylated cortactin protein expression than the RD and CC groups. This increase in cortactin was likely due to the exposure of the rats to the novel environment of the deprivation chambers thus triggering plasticity events. The lack of REMS, however, severely hampered cortactin protein up-regulation and phosphorylation observed in the PC group suggesting an attenuation of plasticity-related events. Thus, these data support a functional link between REMS and cytoskeletal reorganization in the hippocampus, a process that is essential for synaptic plasticity.

  16. The role of actin binding proteins in epithelial morphogenesis: models based upon Listeria movement.

    PubMed

    Golsteyn, R M; Louvard, D; Friederich, E

    1997-10-01

    We summarize recent findings on the organization of the protein actin in eucaryotic cells. In particular we focus on how actin can be used to generate a vectorial force that is required for cell movement. These forces arise from protein molecules that recruit actin to the plasma membrane in such a manner that actin filaments extend outward from the cell body. This type of actin dependent force generation has been described in a nucleation-release model, which is one of several models currently being tested to explain actin dependent cell movement. Data in support of this model has arisen unexpectedly from studies of an intracellular bacteria, Listeria monocytogenes. This bacteria uses actin to propel itself during infection of eucaryotic cells. By studying Listeria movement, the roles of several eucaryotic actin interacting proteins have been identified. One of these is zyxin, a human protein that shares important structural and possibly functional properties with ActA, an actin dependent force generating protein of Listeria. We intend to test the function of these and other actin interacting proteins in a simplified system that should facilitate precise measurement of their properties of force generation in vitro.

  17. Protein domain architectures.

    PubMed

    Mulder, Nicola J

    2010-01-01

    Proteins are composed of functional units, or domains, that can be found alone or in combination with other domains. Analysis of protein domain architectures and the movement of protein domains within and across different genomes provide clues about the evolution of protein function. The classification of proteins into families and domains is provided through publicly available tools and databases that use known protein domains to predict other members in new proteins sequences. Currently at least 80% of the main protein sequence databases can be classified using these tools, thus providing a large data set to work from for analyzing protein domain architectures. Each of the protein domain databases provide intuitive web interfaces for viewing and analyzing their domain classifications and provide their data freely for downloading. Some of the main protein family and domain databases are described here, along with their Web-based tools for analyzing domain architectures.

  18. Understanding the Public Domain.

    ERIC Educational Resources Information Center

    Russell, Carrie

    2003-01-01

    This overview of the public domain covers: defining the public domain; figuring out if a work is protected by copyright; being sure a work is in the public domain; asserting the copyright protection and term; the Creative Commons initiative; building the Information Commons; when permission is needed for using a public domain work; and special…

  19. The study of the Bithorax-complex genes in patterning CCAP neurons reveals a temporal control of neuronal differentiation by Abd-B

    PubMed Central

    Moris-Sanz, M.; Estacio-Gómez, A.; Sánchez-Herrero, E.; Díaz-Benjumea, F. J.

    2015-01-01

    ABSTRACT During development, HOX genes play critical roles in the establishment of segmental differences. In the Drosophila central nervous system, these differences are manifested in the number and type of neurons generated by each neuroblast in each segment. HOX genes can act either in neuroblasts or in postmitotic cells, and either early or late in a lineage. Additionally, they can be continuously required during development or just at a specific stage. Moreover, these features are generally segment-specific. Lately, it has been shown that contrary to what happens in other tissues, where HOX genes define domains of expression, these genes are expressed in individual cells as part of the combinatorial codes involved in cell type specification. In this report we analyse the role of the Bithorax-complex genes – Ultrabithorax, abdominal-A and Abdominal-B – in sculpting the pattern of crustacean cardioactive peptide (CCAP)-expressing neurons. These neurons are widespread in invertebrates, express CCAP, Bursicon and MIP neuropeptides and play major roles in controlling ecdysis. There are two types of CCAP neuron: interneurons and efferent neurons. Our results indicate that Ultrabithorax and Abdominal-A are not necessary for specification of the CCAP-interneurons, but are absolutely required to prevent the death by apoptosis of the CCAP-efferent neurons. Furthermore, Abdominal-B controls by repression the temporal onset of neuropeptide expression in a subset of CCAP-efferent neurons, and a peak of ecdysone hormone at the end of larval life counteracts this repression. Thus, Bithorax complex genes control the developmental appearance of these neuropeptides both temporally and spatially. PMID:26276099

  20. The Drosophila melanogaster flightless-I gene involved in gastrulation and muscle degeneration encodes gelsolin-like and leucine-rich repeat domains and is conserved in Caenorhabditis elegans and humans.

    PubMed Central

    Campbell, H D; Schimansky, T; Claudianos, C; Ozsarac, N; Kasprzak, A B; Cotsell, J N; Young, I G; de Couet, H G; Miklos, G L

    1993-01-01

    Mutations at the flightless-I locus (fliI) of Drosophila melanogaster cause flightlessness or, when severe, incomplete cellularization during early embryogenesis, with subsequent abnormalities in mesoderm invagination and in gastrulation. After chromosome walking, deficiency mapping, and transgenic analysis, we have isolated and characterized flightless-I cDNAs, enabling prediction of the complete amino acid sequence of the 1256-residue protein. Data base searches revealed a homologous gene in Caenorhabditis elegans, and we have isolated and characterized corresponding cDNAs. By using the polymerase chain reaction with nested sets of degenerate oligonucleotide primers based on conserved regions of the C. elegans and D. melanogaster proteins, we have cloned a homologous human cDNA. The predicted C. elegans and human proteins are, respectively, 49% and 58% identical to the D. melanogaster protein. The predicted proteins have significant sequence similarity to the actin-binding protein gelsolin and related proteins and, in addition, have an N-terminal domain consisting of a repetitive amphipathic leucine-rich motif. This repeat is found in D. melanogaster, Saccharomyces cerevisiae, and mammalian proteins known to be involved in cell adhesion and in binding to other proteins. The structure of the maternally expressed flightless-I protein suggests that it may play a key role in embryonic cellularization by interacting with both the cytoskeleton and other cellular components. The presence of a highly conserved homologue in nematodes, flies, and humans is indicative of a fundamental role for this protein in many metazoans. PMID:8248259

  1. Engineering of a bispecific affibody molecule towards HER2 and HER3 by addition of an albumin-binding domain allows for affinity purification and in vivo half-life extension.

    PubMed

    Malm, Magdalena; Bass, Tarek; Gudmundsdotter, Lindvi; Lord, Martin; Frejd, Fredrik Y; Ståhl, Stefan; Löfblom, John

    2014-09-01

    Emerging strategies in cancer biotherapy include the generation and application of bispecific antibodies, targeting two tumor-associated antigens for improved tumor selectivity and potency. Here, an alternative format for bispecific molecules was designed and investigated, in which two Affibody molecules were linked by an albumin-binding domain (ABD). Affibody molecules are small (6 kDa) affinity proteins and this new format allows for engineering of molecules with similar function as full-length bispecific antibodies, but in a dramatically smaller size (around eight-fold smaller). The ABD was intended to function both as a tag for affinity purification as well as for in vivo half-life extension in future preclinical and clinical investigations. Affinity-purified bispecific Affibody molecules, targeting HER2 and HER3, showed simultaneous binding to the three target proteins (HER2, HER3, and albumin) when investigated in biosensor assays. Moreover, simultaneous interactions with the receptors and albumin were demonstrated using flow cytometry on cancer cells. The bispecific Affibody molecules were also able to block ligand-induced phosphorylation of the HER receptors, indicating an anti-proliferative effect. We believe that this compact and flexible format has great potential for developing new potent bispecific affinity proteins in the future, as it combines the benefits of a small size (e.g. improved tissue penetration and reduced cost of goods) with a long circulatory half-life.

  2. Domains and Naive Theories

    PubMed Central

    Gelman, Susan A.; Noles, Nicholaus S.

    2013-01-01

    Human cognition entails domain-specific cognitive processes that influence memory, attention, categorization, problem-solving, reasoning, and knowledge organization. This review examines domain-specific causal theories, which are of particular interest for permitting an examination of how knowledge structures change over time. We first describe the properties of commonsense theories, and how commonsense theories differ from scientific theories, illustrating with children’s classification of biological and non-biological kinds. We next consider the implications of domain-specificity for broader issues regarding cognitive development and conceptual change. We then examine the extent to which domain-specific theories interact, and how people reconcile competing causal frameworks. Future directions for research include examining how different content domains interact, the nature of theory change, the role of context (including culture, language, and social interaction) in inducing different frameworks, and the neural bases for domain-specific reasoning. PMID:24187603

  3. Effect of nucleotides and actin on the orientation of the light chain-binding domain in myosin subfragment 1.

    PubMed

    Smyczynski, C; Kasprzak, A A

    1997-10-28

    The X-ray structure of myosin head (S1) reveals the presence of a long alpha-helical structure that supports both the essential and the regulatory light chains. It has been proposed that small structural changes in the catalytic domain of S1 are amplified by swinging the long alpha-helix (the "lever arm") to produce approximately 11 nm steps. To probe the spatial position of the putative lever in various S1 states, we have measured, by fluorescence resonance energy transfer (FRET), the effect of nucleotides and actin on the distances between Cys-177 of the essential light chain A1 (which is attached to the alpha-helix) and three loci in the catalytic domain. Cys-177 (donor) was labeled with 1,5-IAEDANS. The trinitrophenylated ADP analog (TNP-ADP, acceptor) was used to measure the distance to the active site. Lys-553 at the actin-binding site, labeled with a fluorescein derivative, and Lys-83 modified with trinitrobenzenesulfonic acid served as two other acceptors. FRET measurements were performed for S1 alone, for its complexes with MgADP and MgATP, for the analogs of the transition state of the ATPase reaction, S1.ADP.BeFx, S1.ADP.AlF4, and S1.ADP.VO4, and for acto-S1 in the absence and in the presence of ADP. When the transition state and acto-S1 complexes were formed, the change in the Cys-177 --> Lys-83 distance was <1.1 A, for the distance Cys-177 --> Lys-553, the change was +/-2.5 A. These distance changes correspond to rotations by <10 degrees and approximately 25 degrees, respectively. For the Cys-177 --> TNP-ADP the interprobe separation decreased by approximately 6 A in the presence of BeFx and AlF4- but only 1.9 A in the presence of vanadate; we do not interpret the 6 A change as resulting from the lever rotation. Using the coordinates of the acto-S1 complex, we have computed the expected changes in these distances resulting from rotation of the lever. These changes were much greater than the ones observed. The above results are inconsistent with models

  4. Learning and Domain Adaptation

    NASA Astrophysics Data System (ADS)

    Mansour, Yishay

    Domain adaptation is a fundamental learning problem where one wishes to use labeled data from one or several source domains to learn a hypothesis performing well on a different, yet related, domain for which no labeled data is available. This generalization across domains is a very significant challenge for many machine learning applications and arises in a variety of natural settings, including NLP tasks (document classification, sentiment analysis, etc.), speech recognition (speakers and noise or environment adaptation) and face recognition (different lighting conditions, different population composition).

  5. Visualizing domain wall and reverse domain superconductivity.

    PubMed

    Iavarone, M; Moore, S A; Fedor, J; Ciocys, S T; Karapetrov, G; Pearson, J; Novosad, V; Bader, S D

    2014-08-28

    In magnetically coupled, planar ferromagnet-superconductor (F/S) hybrid structures, magnetic domain walls can be used to spatially confine the superconductivity. In contrast to a superconductor in a uniform applied magnetic field, the nucleation of the superconducting order parameter in F/S structures is governed by the inhomogeneous magnetic field distribution. The interplay between the superconductivity localized at the domain walls and far from the walls leads to effects such as re-entrant superconductivity and reverse domain superconductivity with the critical temperature depending upon the location. Here we use scanning tunnelling spectroscopy to directly image the nucleation of superconductivity at the domain wall in F/S structures realized with Co-Pd multilayers and Pb thin films. Our results demonstrate that such F/S structures are attractive model systems that offer the possibility to control the strength and the location of the superconducting nucleus by applying an external magnetic field, potentially useful to guide vortices for computing application.

  6. Visualizing domain wall and reverse domain superconductivity

    PubMed Central

    Iavarone, M.; Moore, S. A.; Fedor, J.; Ciocys, S. T.; Karapetrov, G.; Pearson, J.; Novosad, V.; Bader, S. D.

    2014-01-01

    In magnetically coupled, planar ferromagnet-superconductor (F/S) hybrid structures, magnetic domain walls can be used to spatially confine the superconductivity. In contrast to a superconductor in a uniform applied magnetic field, the nucleation of the superconducting order parameter in F/S structures is governed by the inhomogeneous magnetic field distribution. The interplay between the superconductivity localized at the domain walls and far from the walls leads to effects such as re-entrant superconductivity and reverse domain superconductivity with the critical temperature depending upon the location. Here we use scanning tunnelling spectroscopy to directly image the nucleation of superconductivity at the domain wall in F/S structures realized with Co-Pd multilayers and Pb thin films. Our results demonstrate that such F/S structures are attractive model systems that offer the possibility to control the strength and the location of the superconducting nucleus by applying an external magnetic field, potentially useful to guide vortices for computing application. PMID:25164004

  7. Causal Learning Across Domains

    ERIC Educational Resources Information Center

    Schulz, Laura E.; Gopnik, Alison

    2004-01-01

    Five studies investigated (a) children's ability to use the dependent and independent probabilities of events to make causal inferences and (b) the interaction between such inferences and domain-specific knowledge. In Experiment 1, preschoolers used patterns of dependence and independence to make accurate causal inferences in the domains of…

  8. Domain wall filters

    SciTech Connect

    Baer, Oliver; Narayanan, Rajamani; Neuberger, Herbert; Witzel, Oliver

    2007-03-15

    We propose using the extra dimension separating the domain walls carrying lattice quarks of opposite handedness to gradually filter out the ultraviolet fluctuations of the gauge fields that are felt by the fermionic excitations living in the bulk. This generalization of the homogeneous domain wall construction has some theoretical features that seem nontrivial.

  9. Modeling Protein Domain Function

    ERIC Educational Resources Information Center

    Baker, William P.; Jones, Carleton "Buck"; Hull, Elizabeth

    2007-01-01

    This simple but effective laboratory exercise helps students understand the concept of protein domain function. They use foam beads, Styrofoam craft balls, and pipe cleaners to explore how domains within protein active sites interact to form a functional protein. The activity allows students to gain content mastery and an understanding of the…

  10. Visualizing Knowledge Domains.

    ERIC Educational Resources Information Center

    Borner, Katy; Chen, Chaomei; Boyack, Kevin W.

    2003-01-01

    Reviews visualization techniques for scientific disciplines and information retrieval and classification. Highlights include historical background of scientometrics, bibliometrics, and citation analysis; map generation; process flow of visualizing knowledge domains; measures and similarity calculations; vector space model; factor analysis;…

  11. Domains in Ferroelectric Nanostructures

    NASA Astrophysics Data System (ADS)

    Gregg, Marty

    2010-03-01

    Ferroelectric materials have great potential in influencing the future of small scale electronics. At a basic level, this is because ferroelectric surfaces are charged, and so interact strongly with charge-carrying metals and semiconductors - the building blocks for all electronic systems. Since the electrical polarity of the ferroelectric can be reversed, surfaces can both attract and repel charges in nearby materials, and can thereby exert complete control over both charge distribution and movement. It should be no surprise, therefore, that microelectronics industries have already looked very seriously at harnessing ferroelectric materials in a variety of applications, from solid state memory chips (FeRAMs) to field effect transistors (FeFETs). In all such applications, switching the direction of the polarity of the ferroelectric is a key aspect of functional behavior. The mechanism for switching involves the field-induced nucleation and growth of domains. Domain coarsening, through domain wall propagation, eventually causes the entire ferroelectric to switch its polar direction. It is thus the existence and behavior of domains that determine the switching response, and ultimately the performance of the ferroelectric device. A major issue, associated with the integration of ferroelectrics into microelectronic devices, has been that the fundamental properties associated with ferroelectrics, when in bulk form, appear to change quite dramatically and unpredictably when at the nanoscale: new modes of behaviour, and different functional characteristics from those seen in bulk appear. For domains, in particular, the proximity of surfaces and boundaries have a dramatic effect: surface tension and depolarizing fields both serve to increase the equilibrium density of domains, such that minor changes in scale or morphology can have major ramifications for domain redistribution. Given the importance of domains in dictating the overall switching characteristics of a device

  12. Just how versatile are domains?

    PubMed Central

    2008-01-01

    Background Creating new protein domain arrangements is a frequent mechanism of evolutionary innovation. While some domains always form the same combinations, others form many different arrangements. This ability, which is often referred to as versatility or promiscuity of domains, its a random evolutionary model in which a domain's promiscuity is based on its relative frequency of domains. Results We show that there is a clear relationship across genomes between the promiscuity of a given domain and its frequency. However, the strength of this relationship differs for different domains. We thus redefine domain promiscuity by defining a new index, DV I ("domain versatility index"), which eliminates the effect of domain frequency. We explore links between a domain's versatility, when unlinked from abundance, and its biological properties. Conclusion Our results indicate that domains occurring as single domain proteins and domains appearing frequently at protein termini have a higher DV I. This is consistent with previous observations that the evolution of domain re-arrangements is primarily driven by fusion of pre-existing arrangements and single domains as well as loss of domains at protein termini. Furthermore, we studied the link between domain age, defined as the first appearance of a domain in the species tree, and the DV I. Contrary to previous studies based on domain promiscuity, it seems as if the DV I is age independent. Finally, we find that contrary to previously reported findings, versatility is lower in Eukaryotes. In summary, our measure of domain versatility indicates that a random attachment process is sufficient to explain the observed distribution of domain arrangements and that several views on domain promiscuity need to be revised. PMID:18854028

  13. Axion domain wall baryogenesis

    SciTech Connect

    Daido, Ryuji; Kitajima, Naoya; Takahashi, Fuminobu

    2015-07-28

    We propose a new scenario of baryogenesis, in which annihilation of axion domain walls generates a sizable baryon asymmetry. Successful baryogenesis is possible for a wide range of the axion mass and decay constant, m≃10{sup 8}–10{sup 13} GeV and f≃10{sup 13}–10{sup 16} GeV. Baryonic isocurvature perturbations are significantly suppressed in our model, in contrast to various spontaneous baryogenesis scenarios in the slow-roll regime. In particular, the axion domain wall baryogenesis is consistent with high-scale inflation which generates a large tensor-to-scalar ratio within the reach of future CMB B-mode experiments. We also discuss the gravitational waves produced by the domain wall annihilation and its implications for the future gravitational wave experiments.

  14. FERM family proteins and their importance in cellular movements and wound healing (review).

    PubMed

    Bosanquet, David C; Ye, Lin; Harding, Keith G; Jiang, Wen G

    2014-07-01

    Motility is a requirement for a number of biological processes, including embryonic development, neuronal development, immune responses, cancer progression and wound healing. Specific to wound healing is the migration of endothelial cells, fibroblasts and other key cellular players into the wound space. Aberrations in wound healing can result in either chronic wounds or abnormally healed wounds. The protein 4.1R, ezrin, radixin, moesin (FERM) superfamily consists of over 40 proteins all containing a three lobed N-terminal FERM domain which binds a variety of cell-membrane associated proteins and lipids. The C-terminal ends of these proteins typically contain an actin-binding domain (ABD). These proteins therefore mediate the linkage between the cell membrane and the actin cytoskeleton, and are involved in cellular movements and migration. Certain FERM proteins have been shown to promote cancer metastasis via this very mechanism. Herein we review the effects of a number of FERM proteins on wound healing and cancer. We show how these proteins typically aid wound healing through their effects on increasing cellular migration and movements, but also typically promote metastasis in cancer. We conclude that FERM proteins play important roles in cellular migration, with markedly different outcomes in the context of cancer and wound healing.

  15. Cellulose binding domain proteins

    DOEpatents

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

    1998-11-17

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

  16. Cellulose binding domain proteins

    DOEpatents

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

    1998-01-01

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

  17. Structure of the 34 kDa F-actin-bundling protein ABP34 from Dictyostelium discoideum.

    PubMed

    Kim, Min-Kyu; Kim, Ji-Hye; Kim, Ji-Sun; Kang, Sa-Ouk

    2015-09-01

    The crystal structure of the 34 kDa F-actin-bundling protein ABP34 from Dictyostelium discoideum was solved by Ca(2+)/S-SAD phasing and refined at 1.89 Å resolution. ABP34 is a calcium-regulated actin-binding protein that cross-links actin filaments into bundles. Its in vitro F-actin-binding and F-actin-bundling activities were confirmed by a co-sedimentation assay and transmission electron microscopy. The co-localization of ABP34 with actin in cells was also verified. ABP34 adopts a two-domain structure with an EF-hand-containing N-domain and an actin-binding C-domain, but has no reported overall structural homologues. The EF-hand is occupied by a calcium ion with a pentagonal bipyramidal coordination as in the canonical EF-hand. The C-domain structure resembles a three-helical bundle and superposes well onto the rod-shaped helical structures of some cytoskeletal proteins. Residues 216-244 in the C-domain form part of the strongest actin-binding sites (193-254) and exhibit a conserved sequence with the actin-binding region of α-actinin and ABP120. Furthermore, the second helical region of the C-domain is kinked by a proline break, offering a convex surface towards the solvent area which is implicated in actin binding. The F-actin-binding model suggests that ABP34 binds to the side of the actin filament and residues 216-244 fit into a pocket between actin subdomains -1 and -2 through hydrophobic interactions. These studies provide insights into the calcium coordination in the EF-hand and F-actin-binding site in the C-domain of ABP34, which are associated through interdomain interactions. PMID:26327373

  18. PTP1B-dependent regulation of receptor tyrosine kinase signaling by the actin-binding protein Mena

    PubMed Central

    Hughes, Shannon K.; Oudin, Madeleine J.; Tadros, Jenny; Neil, Jason; Del Rosario, Amanda; Joughin, Brian A.; Ritsma, Laila; Wyckoff, Jeff; Vasile, Eliza; Eddy, Robert; Philippar, Ulrike; Lussiez, Alisha; Condeelis, John S.; van Rheenen, Jacco; White, Forest; Lauffenburger, Douglas A.; Gertler, Frank B.

    2015-01-01

    During breast cancer progression, alternative mRNA splicing produces functionally distinct isoforms of Mena, an actin regulator with roles in cell migration and metastasis. Aggressive tumor cell subpopulations express MenaINV, which promotes tumor cell invasion by potentiating EGF responses. However, the mechanism by which this occurs is unknown. Here we report that Mena associates constitutively with the tyrosine phosphatase PTP1B and mediates a novel negative feedback mechanism that attenuates receptor tyrosine kinase signaling. On EGF stimulation, complexes containing Mena and PTP1B are recruited to the EGFR, causing receptor dephosphorylation and leading to decreased motility responses. Mena also interacts with the 5′ inositol phosphatase SHIP2, which is important for the recruitment of the Mena-PTP1B complex to the EGFR. When MenaINV is expressed, PTP1B recruitment to the EGFR is impaired, providing a mechanism for growth factor sensitization to EGF, as well as HGF and IGF, and increased resistance to EGFR and Met inhibitors in signaling and motility assays. In sum, we demonstrate that Mena plays an important role in regulating growth factor–induced signaling. Disruption of this attenuation by MenaINV sensitizes tumor cells to low–growth factor concentrations, thereby increasing the migration and invasion responses that contribute to aggressive, malignant cell phenotypes. PMID:26337385

  19. PTP1B-dependent regulation of receptor tyrosine kinase signaling by the actin-binding protein Mena.

    PubMed

    Hughes, Shannon K; Oudin, Madeleine J; Tadros, Jenny; Neil, Jason; Del Rosario, Amanda; Joughin, Brian A; Ritsma, Laila; Wyckoff, Jeff; Vasile, Eliza; Eddy, Robert; Philippar, Ulrike; Lussiez, Alisha; Condeelis, John S; van Rheenen, Jacco; White, Forest; Lauffenburger, Douglas A; Gertler, Frank B

    2015-11-01

    During breast cancer progression, alternative mRNA splicing produces functionally distinct isoforms of Mena, an actin regulator with roles in cell migration and metastasis. Aggressive tumor cell subpopulations express Mena(INV), which promotes tumor cell invasion by potentiating EGF responses. However, the mechanism by which this occurs is unknown. Here we report that Mena associates constitutively with the tyrosine phosphatase PTP1B and mediates a novel negative feedback mechanism that attenuates receptor tyrosine kinase signaling. On EGF stimulation, complexes containing Mena and PTP1B are recruited to the EGFR, causing receptor dephosphorylation and leading to decreased motility responses. Mena also interacts with the 5' inositol phosphatase SHIP2, which is important for the recruitment of the Mena-PTP1B complex to the EGFR. When Mena(INV) is expressed, PTP1B recruitment to the EGFR is impaired, providing a mechanism for growth factor sensitization to EGF, as well as HGF and IGF, and increased resistance to EGFR and Met inhibitors in signaling and motility assays. In sum, we demonstrate that Mena plays an important role in regulating growth factor-induced signaling. Disruption of this attenuation by Mena(INV) sensitizes tumor cells to low-growth factor concentrations, thereby increasing the migration and invasion responses that contribute to aggressive, malignant cell phenotypes.

  20. A small molecule inhibitor of tropomyosin dissociates actin binding from tropomyosin-directed regulation of actin dynamics

    PubMed Central

    Bonello, Teresa T.; Janco, Miro; Hook, Jeff; Byun, Alex; Appaduray, Mark; Dedova, Irina; Hitchcock-DeGregori, Sarah; Hardeman, Edna C.; Stehn, Justine R.; Böcking, Till; Gunning, Peter W.

    2016-01-01

    The tropomyosin family of proteins form end-to-end polymers along the actin filament. Tumour cells rely on specific tropomyosin-containing actin filament populations for growth and survival. To dissect out the role of tropomyosin in actin filament regulation we use the small molecule TR100 directed against the C terminus of the tropomyosin isoform Tpm3.1. TR100 nullifies the effect of Tpm3.1 on actin depolymerisation but surprisingly Tpm3.1 retains the capacity to bind F-actin in a cooperative manner. In vivo analysis also confirms that, in the presence of TR100, fluorescently tagged Tpm3.1 recovers normally into stress fibers. Assembling end-to-end along the actin filament is thereby not sufficient for tropomyosin to fulfil its function. Rather, regulation of F-actin stability by tropomyosin requires fidelity of information communicated at the barbed end of the actin filament. This distinction has significant implications for perturbing tropomyosin-dependent actin filament function in the context of anti-cancer drug development. PMID:26804624

  1. The actin-binding protein EPS8 binds VE-cadherin and modulates YAP localization and signaling

    PubMed Central

    Disanza, Andrea; Bravi, Luca; Barrios-Rodiles, Miriam; Corada, Monica; Frittoli, Emanuela; Savorani, Cecilia; Lampugnani, Maria Grazia; Boggetti, Barbara; Niessen, Carien; Wrana, Jeff L.

    2015-01-01

    Vascular endothelial (VE)–cadherin transfers intracellular signals contributing to vascular hemostasis. Signaling through VE-cadherin requires association and activity of different intracellular partners. Yes-associated protein (YAP)/TAZ transcriptional cofactors are important regulators of cell growth and organ size. We show that EPS8, a signaling adapter regulating actin dynamics, is a novel partner of VE-cadherin and is able to modulate YAP activity. By biochemical and imaging approaches, we demonstrate that EPS8 associates with the VE-cadherin complex of remodeling junctions promoting YAP translocation to the nucleus and transcriptional activation. Conversely, in stabilized junctions, 14–3-3–YAP associates with the VE–cadherin complex, whereas Eps8 is excluded. Junctional association of YAP inhibits nuclear translocation and inactivates its transcriptional activity both in vitro and in vivo in Eps8-null mice. The absence of Eps8 also increases vascular permeability in vivo, but did not induce other major vascular defects. Collectively, we identified novel components of the adherens junction complex, and we introduce a novel molecular mechanism through which the VE-cadherin complex controls YAP transcriptional activity. PMID:26668327

  2. Comparison of the domain and frequency domain state feedbacks

    SciTech Connect

    Zhang, S.Y.

    1986-01-01

    In this paper, we present explicitly the equivalence of the time domain and frequency domain state feedbacks, as well as the dynamic state feedback and a modified frequency domain state feedback, from the closed-loop transfer function point of view. The difference of the two approaches is also shown.

  3. Domain Specific vs Domain General: Implications for Dynamic Assessment

    ERIC Educational Resources Information Center

    Kaniel, Shlomo

    2010-01-01

    The article responds to the need for evidence-based dynamic assessment. The article is divided into two sections: In Part 1 we examine the scientific answer to the question of how far human mental activities and capabilities are domain general (DG) / domain specific (DS). A highly complex answer emerges from the literature review of domains such…

  4. Frequency domain nonlinear optics

    NASA Astrophysics Data System (ADS)

    Legare, Francois

    2016-05-01

    The universal dilemma of gain narrowing occurring in fs amplifiers prevents ultra-high power lasers from delivering few-cycle pulses. This problem is overcome by a new amplification concept: Frequency domain Optical Parametric Amplification - FOPA. It enables simultaneous up-scaling of peak power and amplified spectral bandwidth and can be performed at any wavelength range of conventional amplification schemes, however, with the capability to amplify single cycles of light. The key idea for amplification of octave-spanning spectra without loss of spectral bandwidth is to amplify the broad spectrum ``slice by slice'' in the frequency domain, i.e. in the Fourier plane of a 4f-setup. The striking advantages of this scheme, are its capability to amplify (more than) one octave of bandwidth without shorting the corresponding pulse duration. This is because ultrabroadband phase matching is not defined by the properties of the nonlinear crystal employed but the number of crystals employed. In the same manner, to increase the output energy one simply has to increase the spectral extension in the Fourier plane and to add one more crystal. Thus, increasing pulse energy and shortening its duration accompany each other. A proof of principle experiment was carried out at ALLS on the sub-two cycle IR beam line and yielded record breaking performance in the field of few-cycle IR lasers. 100 μJ two-cycle pulses from a hollow core fibre compression setup were amplified to 1.43mJ without distorting spatial or temporal properties. Pulse duration at the input of FOPA and after FOPA remains the same. Recently, we have started upgrading this system to be pumped by 250 mJ to reach 40 mJ two-cycle IR few-cycle pulses and latest results will be presented at the conference. Furthermore, the extension of the concept of FOPA to other nonlinear optical processes will be discussed. Frequency domain nonlinear optics.

  5. On Probability Domains III

    NASA Astrophysics Data System (ADS)

    Frič, Roman; Papčo, Martin

    2015-12-01

    Domains of generalized probability have been introduced in order to provide a general construction of random events, observables and states. It is based on the notion of a cogenerator and the properties of product. We continue our previous study and show how some other quantum structures fit our categorical approach. We discuss how various epireflections implicitly used in the classical probability theory are related to the transition to fuzzy probability theory and describe the latter probability theory as a genuine categorical extension of the former. We show that the IF-probability can be studied via the fuzzy probability theory. We outline a "tensor modification" of the fuzzy probability theory.

  6. Transfer of high domain knowledge to a similar domain.

    PubMed

    Jessup, Ryan K

    2009-01-01

    Researchers have widely examined domain knowledge yet rarely investigate the transfer of knowledge from one domain to another. This study sought to fill in the literature gap concerning the impact of domain knowledge on memory in a similar situation. Specifically, this study examined whether high knowledge of baseball could enhance memory for the similar yet unknown domain of cricket, using a 2 (knowledge) x 2 (prime) design. An interaction occurred, indicating that when primed, baseball knowledge improves memory for cricket events in participants with high baseball knowledge but reduces memory in their low-knowledge counterparts. These results suggest that extensive knowledge in one domain allows it to serve as an organizational framework for incoming information in a similar domain; conversely, priming poorly understood domain knowledge results in negative transfer.

  7. Transfer of high domain knowledge to a similar domain.

    PubMed

    Jessup, Ryan K

    2009-01-01

    Researchers have widely examined domain knowledge yet rarely investigate the transfer of knowledge from one domain to another. This study sought to fill in the literature gap concerning the impact of domain knowledge on memory in a similar situation. Specifically, this study examined whether high knowledge of baseball could enhance memory for the similar yet unknown domain of cricket, using a 2 (knowledge) x 2 (prime) design. An interaction occurred, indicating that when primed, baseball knowledge improves memory for cricket events in participants with high baseball knowledge but reduces memory in their low-knowledge counterparts. These results suggest that extensive knowledge in one domain allows it to serve as an organizational framework for incoming information in a similar domain; conversely, priming poorly understood domain knowledge results in negative transfer. PMID:19353932

  8. STAS Domain Structure and Function

    PubMed Central

    Sharma, Alok K.; Rigby, Alan C.; Alper, Seth L.

    2011-01-01

    Pendrin shares with nearly all SLC26/SulP anion transporters a carboxy-terminal cytoplasmic segment organized around a Sulfate Transporter and Anti-Sigma factor antagonist (STAS) domain. STAS domains of divergent amino acid sequence exhibit a conserved fold of 4 β strands interspersed among 5 α helices. The first STAS domain proteins studied were single-domain anti-sigma factor antagonists (anti-anti-σ). These anti-anti-σ indirectly stimulate bacterial RNA polymerase by inactivating inhibitory anti-σ kinases, liberating σ factors to direct specific transcription of target genes or operons. Some STAS domains are nucleotide-binding phosphoproteins or nucleotidases. Others are interaction/transduction modules within multidomain sensors of light, oxygen and other gasotransmitters, cyclic nucleotides, inositol phosphates, and G proteins. Additional multidomain STAS protein sequences suggest functions in sensing, metabolism, or transport of nutrients such as sugars, amino acids, lipids, anions, vitamins, or hydrocarbons. Still other multidomain STAS polypeptides include histidine and serine/threonine kinase domains and ligand-activated transcription factor domains. SulP/SLC26 STAS domains and adjacent sequences interact with other transporters, cytoskeletal scaffolds, and with enzymes metabolizing transported anion substrates, forming putative metabolons. STAS domains are central to membrane targeting of many SulP/SLC26 anion transporters, and STAS domain mutations are associated with at least three human recessive diseases. This review summarizes STAS domain structure and function. PMID:22116355

  9. Spectral Domain Phase Microscopy

    NASA Astrophysics Data System (ADS)

    Hendargo, Hansford C.; Ellerbee, Audrey K.; Izatt, Joseph A.

    Spectral domain phase microscopy (SDPM) is a functional extension of optical coherence tomography (OCT) using common-path interferometry to produce phase-referenced images of dynamic samples. Like OCT, axial resolution in SDPM is determined by the source coherence length, while lateral resolution is limited by diffraction in the microscope optics. However, the quantitative phase information SDPM generates is sensitive to nanometer-scale displacements of scattering structures. The use of a common-path optical geometry yields an imaging system with high phase stability. Due to coherence gating, SDPM can achieve full depth discrimination, allowing for independent motion resolution of subcellular structures throughout the sample volume. Here we review the basic theory of OCT and SDPM along with applications of SDPM in cellular imaging to measure topology, Doppler flow in single-celled organisms, time-resolved motions, rheological information of the cytoskeleton, and optical signaling of neural activation. Phase imaging limitations, artifacts, and sensitivity considerations are discussed.

  10. Beyond the Number Domain

    PubMed Central

    Cantlon, Jessica F.; Platt, Michael L.; Brannon, Elizabeth M.

    2009-01-01

    In a world without numbers, we would be unable to build a skyscraper, hold a national election, plan a wedding, or pay for a chicken at the market. The numerical symbols used in all these behaviors build on the approximate number system (ANS) which represents the number of discrete objects or events as a continuous mental magnitude. In this review, we first discuss evidence that the ANS bears a set of behavioral and brain signatures that are universally displayed across animal species, human cultures, and development. We then turn to the question of whether the ANS constitutes a specialized cognitive and neural domain--a question central to understanding how this system works, the nature of its evolutionary and developmental trajectory, and its physical instantiation in the brain. PMID:19131268

  11. Rational identification of enoxacin as a novel V-ATPase-directed osteoclast inhibitor.

    PubMed

    Toro, Edgardo J; Ostrov, David A; Wronski, Thomas J; Holliday, L Shannon

    2012-03-01

    Binding between vacuolar H+-ATPases (V-ATPases) and microfilaments is mediated by an actin binding domain in the B-subunit. Both isoforms of mammalian B-subunit bind microfilaments with high affinity. A similar actinbinding activity has been demonstrated in the B-subunit of yeast. A conserved "profilin-like" domain in the B-subunit mediates this actin-binding activity, named due to its sequence and structural similarity to an actin-binding surface of the canonical actin binding protein profilin. Subtle mutations in the "profilin-like" domain eliminate actin binding activity without disrupting the ability of the altered protein to associate with the other subunits of V-ATPase to form a functional proton pump. Analysis of these mutated B-subunits suggests that the actin-binding activity is not required for the "housekeeping" functions of V-ATPases, but is important for certain specialized roles. In osteoclasts, the actin-binding activity is required for transport of V-ATPases to the plasma membrane, a prerequisite for bone resorption. A virtual screen led to the identification of enoxacin as a small molecule that bound to the actin-binding surface of the B2-subunit and competitively inhibited B2-subunit and actin interaction. Enoxacin disrupted osteoclastic bone resorption in vitro, but did not affect osteoblast formation or mineralization. Recently, enoxacin was identified as an inhibitor of the virulence of Candida albicans and more importantly of cancer growth and metastasis. Efforts are underway to determine the mechanisms by which enoxacin and other small molecule inhibitors of B2 and microfilament binding interaction selectively block bone resorption, the virulence of Candida, cancer growth, and metastasis.

  12. Characterization of the pre-force-generation state in the actomyosin cross-bridge cycle

    PubMed Central

    Sun, Mingxuan; Rose, Michael B.; Ananthanarayanan, Shobana K.; Jacobs, Donald J.; Yengo, Christopher M.

    2008-01-01

    Myosin is an actin-based motor protein that generates force by cycling between actin-attached (strong binding: ADP or rigor) and actin-detached (weak binding: ATP or ADP·Pi) states during its ATPase cycle. However, it remains unclear what specific conformational changes in the actin binding site take place on binding to actin, and how these structural changes lead to product release and the production of force and motion. We studied the dynamics of the actin binding region of myosin V by using fluorescence resonance energy transfer (FRET) to monitor conformational changes in the upper-50-kDa domain of the actin binding cleft in the weak and strong actin binding states. Steady-state and lifetime data monitoring the FRET signal suggest that the cleft is in a more open conformation in the weak actin binding states. Transient kinetic experiments suggest that a rapid conformational change occurs, which is consistent with cleft closure before actin-activated phosphate release. Our results have identified a pre-force-generation actomyosin ADP·Pi state, and suggest force generation may occur from a state not yet seen by crystallography in which the actin binding cleft and the nucleotide binding pocket are closed. Computational modeling uncovers dramatic changes in the rigidity of the upper-50-kDa domain in different nucleotide states, which suggests that the intrinsic flexibility of this domain allows myosin motors to accomplish simultaneous tight nucleotide binding (closed nucleotide binding pocket) and high-affinity actin binding (closed actin binding cleft). PMID:18552179

  13. Multifunctionalities driven by ferroic domains

    SciTech Connect

    Yang, J. C.; Huang, Y. L.; Chu, Y. H.; He, Q.

    2014-08-14

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

  14. Dynamical domain wall and localization

    NASA Astrophysics Data System (ADS)

    Toyozato, Yuta; Higuchi, Masafumi; Nojiri, Shin'ichi

    2016-03-01

    Based on the previous works (Toyozato et al., 2013 [24]; Higuchi and Nojiri, 2014 [25]), we investigate the localization of the fields on the dynamical domain wall, where the four-dimensional FRW universe is realized on the domain wall in the five-dimensional space-time. Especially we show that the chiral spinor can localize on the domain wall, which has not been succeeded in the past works as the seminal work in George et al. (2009) [23].

  15. Mapping the Moral Domain

    PubMed Central

    Graham, Jesse; Nosek, Brian A.; Haidt, Jonathan; Iyer, Ravi; Koleva, Spassena; Ditto, Peter H.

    2010-01-01

    The moral domain is broader than the empathy and justice concerns assessed by existing measures of moral competence, and it is not just a subset of the values assessed by value inventories. To fill the need for reliable and theoretically-grounded measurement of the full range of moral concerns, we developed the Moral Foundations Questionnaire (MFQ) based on a theoretical model of five universally available (but variably developed) sets of moral intuitions: Harm/care, Fairness/reciprocity, Ingroup/loyalty, Authority/respect, and Purity/sanctity. We present evidence for the internal and external validity of the scale and the model, and in doing so present new findings about morality: 1. Comparative model fitting of confirmatory factor analyses provides empirical justification for a five-factor structure of moral concerns. 2. Convergent/discriminant validity evidence suggests that moral concerns predict personality features and social group attitudes not previously considered morally relevant. 3. We establish pragmatic validity of the measure in providing new knowledge and research opportunities concerning demographic and cultural differences in moral intuitions. These analyses provide evidence for the usefulness of Moral Foundations Theory in simultaneously increasing the scope and sharpening the resolution of psychological views of morality. PMID:21244182

  16. Hydrophobic Compounds Reshape Membrane Domains

    PubMed Central

    Barnoud, Jonathan; Rossi, Giulia; Marrink, Siewert J.; Monticelli, Luca

    2014-01-01

    Cell membranes have a complex lateral organization featuring domains with distinct composition, also known as rafts, which play an essential role in cellular processes such as signal transduction and protein trafficking. In vivo, perturbations of membrane domains (e.g., by drugs or lipophilic compounds) have major effects on the activity of raft-associated proteins and on signaling pathways, but they are difficult to characterize because of the small size of the domains, typically below optical resolution. Model membranes, instead, can show macroscopic phase separation between liquid-ordered and liquid-disordered domains, and they are often used to investigate the driving forces of membrane lateral organization. Studies in model membranes have shown that some lipophilic compounds perturb membrane domains, but it is not clear which chemical and physical properties determine domain perturbation. The mechanisms of domain stabilization and destabilization are also unknown. Here we describe the effect of six simple hydrophobic compounds on the lateral organization of phase-separated model membranes consisting of saturated and unsaturated phospholipids and cholesterol. Using molecular simulations, we identify two groups of molecules with distinct behavior: aliphatic compounds promote lipid mixing by distributing at the interface between liquid-ordered and liquid-disordered domains; aromatic compounds, instead, stabilize phase separation by partitioning into liquid-disordered domains and excluding cholesterol from the disordered domains. We predict that relatively small concentrations of hydrophobic species can have a broad impact on domain stability in model systems, which suggests possible mechanisms of action for hydrophobic compounds in vivo. PMID:25299598

  17. On Probability Domains

    NASA Astrophysics Data System (ADS)

    Frič, Roman; Papčo, Martin

    2010-12-01

    Motivated by IF-probability theory (intuitionistic fuzzy), we study n-component probability domains in which each event represents a body of competing components and the range of a state represents a simplex S n of n-tuples of possible rewards-the sum of the rewards is a number from [0,1]. For n=1 we get fuzzy events, for example a bold algebra, and the corresponding fuzzy probability theory can be developed within the category ID of D-posets (equivalently effect algebras) of fuzzy sets and sequentially continuous D-homomorphisms. For n=2 we get IF-events, i.e., pairs ( μ, ν) of fuzzy sets μ, ν∈[0,1] X such that μ( x)+ ν( x)≤1 for all x∈ X, but we order our pairs (events) coordinatewise. Hence the structure of IF-events (where ( μ 1, ν 1)≤( μ 2, ν 2) whenever μ 1≤ μ 2 and ν 2≤ ν 1) is different and, consequently, the resulting IF-probability theory models a different principle. The category ID is cogenerated by I=[0,1] (objects of ID are subobjects of powers I X ), has nice properties and basic probabilistic notions and constructions are categorical. For example, states are morphisms. We introduce the category S n D cogenerated by Sn=\\{(x1,x2,ldots ,xn)in In;sum_{i=1}nxi≤ 1\\} carrying the coordinatewise partial order, difference, and sequential convergence and we show how basic probability notions can be defined within S n D.

  18. Fractional diffusion on bounded domains

    SciTech Connect

    Defterli, Ozlem; D'Elia, Marta; Du, Qiang; Gunzburger, Max Donald; Lehoucq, Richard B.; Meerschaert, Mark M.

    2015-03-13

    We found that the mathematically correct specification of a fractional differential equation on a bounded domain requires specification of appropriate boundary conditions, or their fractional analogue. In this paper we discuss the application of nonlocal diffusion theory to specify well-posed fractional diffusion equations on bounded domains.

  19. Diversity in protein domain superfamilies

    PubMed Central

    Das, Sayoni; Dawson, Natalie L; Orengo, Christine A

    2015-01-01

    Whilst ∼93% of domain superfamilies appear to be relatively structurally and functionally conserved based on the available data from the CATH-Gene3D domain classification resource, the remainder are much more diverse. In this review, we consider how domains in some of the most ubiquitous and promiscuous superfamilies have evolved, in particular the plasticity in their functional sites and surfaces which expands the repertoire of molecules they interact with and actions performed on them. To what extent can we identify a core function for these superfamilies which would allow us to develop a ‘domain grammar of function’ whereby a protein's biological role can be proposed from its constituent domains? Clearly the first step is to understand the extent to which these components vary and how changes in their molecular make-up modifies function. PMID:26451979

  20. Separated matter and antimatter domains with vanishing domain walls

    SciTech Connect

    Dolgov, A.D.; Godunov, S.I.; Rudenko, A.S.; Tkachev, I.I. E-mail: sgodunov@itep.ru E-mail: tkachev@ms2.inr.ac.ru

    2015-10-01

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

  1. Modeling software systems by domains

    NASA Technical Reports Server (NTRS)

    Dippolito, Richard; Lee, Kenneth

    1992-01-01

    The Software Architectures Engineering (SAE) Project at the Software Engineering Institute (SEI) has developed engineering modeling techniques that both reduce the complexity of software for domain-specific computer systems and result in systems that are easier to build and maintain. These techniques allow maximum freedom for system developers to apply their domain expertise to software. We have applied these techniques to several types of applications, including training simulators operating in real time, engineering simulators operating in non-real time, and real-time embedded computer systems. Our modeling techniques result in software that mirrors both the complexity of the application and the domain knowledge requirements. We submit that the proper measure of software complexity reflects neither the number of software component units nor the code count, but the locus of and amount of domain knowledge. As a result of using these techniques, domain knowledge is isolated by fields of engineering expertise and removed from the concern of the software engineer. In this paper, we will describe kinds of domain expertise, describe engineering by domains, and provide relevant examples of software developed for simulator applications using the techniques.

  2. Concept Convergence in Empirical Domains

    NASA Astrophysics Data System (ADS)

    Ontañón, Santiago; Plaza, Enric

    How to achieve shared meaning is a significant issue when more than one intelligent agent is involved in the same domain. We define the task of concept convergence, by which intelligent agents can achieve a shared, agreed-upon meaning of a concept (restricted to empirical domains). For this purpose we present a framework that, integrating computational argumentation and inductive concept learning, allows a pair of agents to (1) learn a concept in an empirical domain, (2) argue about the concept's meaning, and (3) reach a shared agreed-upon concept definition. We apply this framework to marine sponges, a biological domain where the actual definitions of concepts such as orders, families and species are currently open to discussion. An experimental evaluation on marine sponges shows that concept convergence is achieved, within a reasonable number of interchanged arguments, and reaching short and accurate definitions (with respect to precision and recall).

  3. Domain and Specification Models for Software Engineering

    NASA Technical Reports Server (NTRS)

    Iscoe, Neil; Liu, Zheng-Yang; Feng, Guohui

    1992-01-01

    This paper discusses our approach to representing application domain knowledge for specific software engineering tasks. Application domain knowledge is embodied in a domain model. Domain models are used to assist in the creation of specification models. Although many different specification models can be created from any particular domain model, each specification model is consistent and correct with respect to the domain model. One aspect of the system-hierarchical organization is described in detail.

  4. Localization of resistive domains in inhomogeneous superconductors

    SciTech Connect

    Gurevich, A.V.; Mints, R.G.

    1981-01-01

    The properties of resistive domains due to the Joule heating in inhomogeneous superconductors with transport currents are studied. The equilibrium of a domain at an inhomogeneity of arbitrary type and with dimensions much smaller than the dimensions of the domain is investigated. It is shown that resistive domains can become localized at inhomogeneities. The temperature distribution in a domain and the current--voltage characteristic of the domain are determined. The stability of localized domains is discussed. It is shown that such domains give rise to a hysteresis in the destruction (recovery) of the superconductivity by the transport current.

  5. Predicting cognitive change within domains

    PubMed Central

    Duff, Kevin; Beglinger, Leigh J.; Moser, David J.; Paulsen, Jane S.

    2010-01-01

    Standardized regression based (SRB) formulas, a method for predicting cognitive change across time, traditionally use baseline performance on a neuropsychological measure to predict future performance on that same measure. However, there are instances in which the same tests may not be given at follow-up assessments (e.g., lack of continuity of provider, avoiding practice effects). The current study sought to expand this methodology by developing SRBs to predict performance on different tests within the same cognitive domain. Using a sample of 127 non-demented community-dwelling older adults assessed at baseline and after one year, two sets of SRBs were developed: 1. those predicting performance on the same test, and 2. those predicting performance on a different test within the same cognitive domain. The domains examined were learning and memory, processing speed, and language. Across both sets of SRBs, one year scores were significantly predicted by baseline scores, especially for the learning and memory and processing speed measures. Although SRBs developed for the same test were comparable to those developed for different tests within the same domain, less variance was accounted for as tests became less similar. The current results lend preliminary support for additional development of SRBs, both for same- and different-tests, as well as beginning to examine domain-based SRBs. PMID:20358479

  6. Functional domain walls in multiferroics

    NASA Astrophysics Data System (ADS)

    Meier, Dennis

    2015-11-01

    During the last decade a wide variety of novel and fascinating correlation phenomena has been discovered at domain walls in multiferroic bulk systems, ranging from unusual electronic conductance to inseparably entangled spin and charge degrees of freedom. The domain walls represent quasi-2D functional objects that can be induced, positioned, and erased on demand, bearing considerable technological potential for future nanoelectronics. Most of the challenges that remain to be solved before turning related device paradigms into reality, however, still fall in the field of fundamental condensed matter physics and materials science. In this topical review seminal experimental findings gained on electric and magnetic domain walls in multiferroic bulk materials are addressed. A special focus is put on the physical properties that emerge at so-called charged domain walls and the added functionality that arises from coexisting magnetic order. The research presented in this review highlights that we are just entering a whole new world of intriguing nanoscale physics that is yet to be explored in all its details. The goal is to draw attention to the persistent challenges and identify future key directions for the research on functional domain walls in multiferroics.

  7. Gradient Domain Guided Image Filtering.

    PubMed

    Kou, Fei; Chen, Weihai; Wen, Changyun; Li, Zhengguo

    2015-11-01

    Guided image filter (GIF) is a well-known local filter for its edge-preserving property and low computational complexity. Unfortunately, the GIF may suffer from halo artifacts, because the local linear model used in the GIF cannot represent the image well near some edges. In this paper, a gradient domain GIF is proposed by incorporating an explicit first-order edge-aware constraint. The edge-aware constraint makes edges be preserved better. To illustrate the efficiency of the proposed filter, the proposed gradient domain GIF is applied for single-image detail enhancement, tone mapping of high dynamic range images and image saliency detection. Both theoretical analysis and experimental results prove that the proposed gradient domain GIF can produce better resultant images, especially near the edges, where halos appear in the original GIF. PMID:26285153

  8. Faraday instability in deformable domains

    NASA Astrophysics Data System (ADS)

    Pucci, Giuseppe; Ben Amar, Martine; Couder, Yves

    2014-11-01

    We investigate the Faraday instability in floating liquid lenses, as an example of hydrodynamic instability that develops in a domain with flexible boundaries. We show that a mutual adaptation of the instability pattern and the domain shape occurs, as a result of the competition between the wave radiation pressure and the capillary response of the lens border. Two archetypes of behaviour are observed. In the first, stable shapes are obtained experimentally and predicted theoretically as the exact solutions of a Riccati equation, and they result from the equilibrium between wave radiation pressure and capillarity. In the second, the radiation pressure exceeds the capillary response of the lens border and leads to non-equilibrium behaviours, with breaking into smaller domains that have a complex dynamics including spontaneous propagation. The authors are grateful to Université Franco-Italienne (UFI) for financial support.

  9. A Method to Examine Content Domain Structures

    ERIC Educational Resources Information Center

    D'Agostino, Jerome; Karpinski, Aryn; Welsh, Megan

    2011-01-01

    After a test is developed, most content validation analyses shift from ascertaining domain definition to studying domain representation and relevance because the domain is assumed to be set once a test exists. We present an approach that allows for the examination of alternative domain structures based on extant test items. In our example based on…

  10. Domain Specificity and Variability in Cognitive Development.

    ERIC Educational Resources Information Center

    Gelman, Rochel

    2000-01-01

    Maintains that there are core-specific and non-core-specific domains of knowledge, but that only the core-specific domains benefit from innate skeletal structures. Asserts that core skeletal domains are universally shared, even though their particular foci may vary. Emphasizes that individuals vary in terms of the noncore domains they acquire.…

  11. Cellulose binding domain fusion proteins

    DOEpatents

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

    1998-02-17

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

  12. Development in the Food Domain.

    ERIC Educational Resources Information Center

    Rozin, Paul

    1990-01-01

    Discusses problems of general interest in developmental psychology that can be successfully studied in the domain of food; these include (1) development of food likes and dislikes; (2) establishment of the edible/inedible distinction; (3) disgust and contagion; (4) transgenerational communication of preferences; and (5) transition to food…

  13. Cellulose binding domain fusion proteins

    DOEpatents

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

    1998-01-01

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

  14. In the Multi-domain Protein Adenylate Kinase, Domain Insertion Facilitates Cooperative Folding while Accommodating Function at Domain Interfaces

    PubMed Central

    Giri Rao, V. V. Hemanth; Gosavi, Shachi

    2014-01-01

    Having multiple domains in proteins can lead to partial folding and increased aggregation. Folding cooperativity, the all or nothing folding of a protein, can reduce this aggregation propensity. In agreement with bulk experiments, a coarse-grained structure-based model of the three-domain protein, E. coli Adenylate kinase (AKE), folds cooperatively. Domain interfaces have previously been implicated in the cooperative folding of multi-domain proteins. To understand their role in AKE folding, we computationally create mutants with deleted inter-domain interfaces and simulate their folding. We find that inter-domain interfaces play a minor role in the folding cooperativity of AKE. On further analysis, we find that unlike other multi-domain proteins whose folding has been studied, the domains of AKE are not singly-linked. Two of its domains have two linkers to the third one, i.e., they are inserted into the third one. We use circular permutation to modify AKE chain-connectivity and convert inserted-domains into singly-linked domains. We find that domain insertion in AKE achieves the following: (1) It facilitates folding cooperativity even when domains have different stabilities. Insertion constrains the N- and C-termini of inserted domains and stabilizes their folded states. Therefore, domains that perform conformational transitions can be smaller with fewer stabilizing interactions. (2) Inter-domain interactions are not needed to promote folding cooperativity and can be tuned for function. In AKE, these interactions help promote conformational dynamics limited catalysis. Finally, using structural bioinformatics, we suggest that domain insertion may also facilitate the cooperative folding of other multi-domain proteins. PMID:25393408

  15. Cross-domain human action recognition.

    PubMed

    Bian, Wei; Tao, Dacheng; Rui, Yong

    2012-04-01

    Conventional human action recognition algorithms cannot work well when the amount of training videos is insufficient. We solve this problem by proposing a transfer topic model (TTM), which utilizes information extracted from videos in the auxiliary domain to assist recognition tasks in the target domain. The TTM is well characterized by two aspects: 1) it uses the bag-of-words model trained from the auxiliary domain to represent videos in the target domain; and 2) it assumes each human action is a mixture of a set of topics and uses the topics learned from the auxiliary domain to regularize the topic estimation in the target domain, wherein the regularization is the summation of Kullback-Leibler divergences between topic pairs of the two domains. The utilization of the auxiliary domain knowledge improves the generalization ability of the learned topic model. Experiments on Weizmann and KTH human action databases suggest the effectiveness of the proposed TTM for cross-domain human action recognition.

  16. Spline interpolation on unbounded domains

    NASA Astrophysics Data System (ADS)

    Skeel, Robert D.

    2016-06-01

    Spline interpolation is a splendid tool for multiscale approximation on unbounded domains. In particular, it is well suited for use by the multilevel summation method (MSM) for calculating a sum of pairwise interactions for a large set of particles in linear time. Outlined here is an algorithm for spline interpolation on unbounded domains that is efficient and elegant though not so simple. Further gains in efficiency are possible via quasi-interpolation, which compromises collocation but with minimal loss of accuracy. The MSM, which may also be of value for continuum models, embodies most of the best features of both hierarchical clustering methods (tree methods, fast multipole methods, hierarchical matrix methods) and FFT-based 2-level methods (particle-particle particle-mesh methods, particle-mesh Ewald methods).

  17. Gabor domain optical coherence microscopy

    NASA Astrophysics Data System (ADS)

    Murali, Supraja

    Time domain Optical Coherence Tomography (TD-OCT), first reported in 1991, makes use of the low temporal coherence properties of a NIR broadband laser to create depth sectioning of up to 2mm under the surface using optical interferometry and point to point scanning. Prior and ongoing work in OCT in the research community has concentrated on improving axial resolution through the development of broadband sources and speed of image acquisition through new techniques such as Spectral domain OCT (SD-OCT). In SD-OCT, an entire depth scan is acquired at once with a low numerical aperture (NA) objective lens focused at a fixed point within the sample. In this imaging geometry, a longer depth of focus is achieved at the expense of lateral resolution, which is typically limited to 10 to 20 mum. Optical Coherence Microscopy (OCM), introduced in 1994, combined the advantages of high axial resolution obtained in OCT with high lateral resolution obtained by increasing the NA of the microscope placed in the sample arm. However, OCM presented trade-offs caused by the inverse quadratic relationship between the NA and the DOF of the optics used. For applications requiring high lateral resolution, such as cancer diagnostics, several solutions have been proposed including the periodic manual re-focusing of the objective lens in the time domain as well as the spectral domain C-mode configuration in order to overcome the loss in lateral resolution outside the DOF. In this research, we report for the first time, high speed, sub-cellular imaging (lateral resolution of 2 mum) in OCM using a Gabor domain image processing algorithm with a custom designed and fabricated dynamic focus microscope interfaced to a Ti:Sa femtosecond laser centered at 800 nm within an SD-OCM configuration. It is envisioned that this technology will provide a non-invasive replacement for the current practice of multiple biopsies for skin cancer diagnosis. The research reported here presents three important advances

  18. Frequency domain optical parametric amplification

    NASA Astrophysics Data System (ADS)

    Schmidt, Bruno E.; Thiré, Nicolas; Boivin, Maxime; Laramée, Antoine; Poitras, François; Lebrun, Guy; Ozaki, Tsuneyuki; Ibrahim, Heide; Légaré, François

    2014-05-01

    Today’s ultrafast lasers operate at the physical limits of optical materials to reach extreme performances. Amplification of single-cycle laser pulses with their corresponding octave-spanning spectra still remains a formidable challenge since the universal dilemma of gain narrowing sets limits for both real level pumped amplifiers as well as parametric amplifiers. We demonstrate that employing parametric amplification in the frequency domain rather than in time domain opens up new design opportunities for ultrafast laser science, with the potential to generate single-cycle multi-terawatt pulses. Fundamental restrictions arising from phase mismatch and damage threshold of nonlinear laser crystals are not only circumvented but also exploited to produce a synergy between increased seed spectrum and increased pump energy. This concept was successfully demonstrated by generating carrier envelope phase stable, 1.43 mJ two-cycle pulses at 1.8 μm wavelength.

  19. Certifying Domain-Specific Policies

    NASA Technical Reports Server (NTRS)

    Lowry, Michael; Pressburger, Thomas; Rosu, Grigore; Koga, Dennis (Technical Monitor)

    2001-01-01

    Proof-checking code for compliance to safety policies potentially enables a product-oriented approach to certain aspects of software certification. To date, previous research has focused on generic, low-level programming-language properties such as memory type safety. In this paper we consider proof-checking higher-level domain -specific properties for compliance to safety policies. The paper first describes a framework related to abstract interpretation in which compliance to a class of certification policies can be efficiently calculated Membership equational logic is shown to provide a rich logic for carrying out such calculations, including partiality, for certification. The architecture for a domain-specific certifier is described, followed by an implemented case study. The case study considers consistency of abstract variable attributes in code that performs geometric calculations in Aerospace systems.

  20. Frequency domain optical parametric amplification

    PubMed Central

    Schmidt, Bruno E.; Thiré, Nicolas; Boivin, Maxime; Laramée, Antoine; Poitras, François; Lebrun, Guy; Ozaki, Tsuneyuki; Ibrahim, Heide; Légaré, François

    2014-01-01

    Today’s ultrafast lasers operate at the physical limits of optical materials to reach extreme performances. Amplification of single-cycle laser pulses with their corresponding octave-spanning spectra still remains a formidable challenge since the universal dilemma of gain narrowing sets limits for both real level pumped amplifiers as well as parametric amplifiers. We demonstrate that employing parametric amplification in the frequency domain rather than in time domain opens up new design opportunities for ultrafast laser science, with the potential to generate single-cycle multi-terawatt pulses. Fundamental restrictions arising from phase mismatch and damage threshold of nonlinear laser crystals are not only circumvented but also exploited to produce a synergy between increased seed spectrum and increased pump energy. This concept was successfully demonstrated by generating carrier envelope phase stable, 1.43 mJ two-cycle pulses at 1.8 μm wavelength. PMID:24805968

  1. Domain decomposition methods in aerodynamics

    NASA Technical Reports Server (NTRS)

    Venkatakrishnan, V.; Saltz, Joel

    1990-01-01

    Compressible Euler equations are solved for two-dimensional problems by a preconditioned conjugate gradient-like technique. An approximate Riemann solver is used to compute the numerical fluxes to second order accuracy in space. Two ways to achieve parallelism are tested, one which makes use of parallelism inherent in triangular solves and the other which employs domain decomposition techniques. The vectorization/parallelism in triangular solves is realized by the use of a recording technique called wavefront ordering. This process involves the interpretation of the triangular matrix as a directed graph and the analysis of the data dependencies. It is noted that the factorization can also be done in parallel with the wave front ordering. The performances of two ways of partitioning the domain, strips and slabs, are compared. Results on Cray YMP are reported for an inviscid transonic test case. The performances of linear algebra kernels are also reported.

  2. Flexible time domain averaging technique

    NASA Astrophysics Data System (ADS)

    Zhao, Ming; Lin, Jing; Lei, Yaguo; Wang, Xiufeng

    2013-09-01

    Time domain averaging(TDA) is essentially a comb filter, it cannot extract the specified harmonics which may be caused by some faults, such as gear eccentric. Meanwhile, TDA always suffers from period cutting error(PCE) to different extent. Several improved TDA methods have been proposed, however they cannot completely eliminate the waveform reconstruction error caused by PCE. In order to overcome the shortcomings of conventional methods, a flexible time domain averaging(FTDA) technique is established, which adapts to the analyzed signal through adjusting each harmonic of the comb filter. In this technique, the explicit form of FTDA is first constructed by frequency domain sampling. Subsequently, chirp Z-transform(CZT) is employed in the algorithm of FTDA, which can improve the calculating efficiency significantly. Since the signal is reconstructed in the continuous time domain, there is no PCE in the FTDA. To validate the effectiveness of FTDA in the signal de-noising, interpolation and harmonic reconstruction, a simulated multi-components periodic signal that corrupted by noise is processed by FTDA. The simulation results show that the FTDA is capable of recovering the periodic components from the background noise effectively. Moreover, it can improve the signal-to-noise ratio by 7.9 dB compared with conventional ones. Experiments are also carried out on gearbox test rigs with chipped tooth and eccentricity gear, respectively. It is shown that the FTDA can identify the direction and severity of the eccentricity gear, and further enhances the amplitudes of impulses by 35%. The proposed technique not only solves the problem of PCE, but also provides a useful tool for the fault symptom extraction of rotating machinery.

  3. Field-Domain Ion Spectrometry

    NASA Technical Reports Server (NTRS)

    Bowers, W. D.; Chuan, R. L.

    1992-01-01

    Field-domain ion spectrometry (FDIS) is variant of established technique known as ion-mobility spectrometry. Operates at atmospheric pressure and only requires small pump to draw air sample into instrument. Strength of retarding electric field varied to distinguish among ions of different mobilities. New concept offers potential for development of small, (hand-held), low-power, portable devices detecting airborne chemical substances in real-time at concentrations at parts-per-billion level.

  4. Pyramidal inversion domain boundaries revisited

    SciTech Connect

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

    2011-10-03

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

  5. Dynamics of domain wall networks

    SciTech Connect

    Eto, Minoru; Fujimori, Toshiaki; Nagashima, Takayuki; Sakai, Norisuke; Nitta, Muneto; Ohashi, Keisuke

    2007-12-15

    Networks or webs of domain walls are admitted in Abelian or non-Abelian gauge theory coupled to fundamental Higgs fields with complex masses. We examine the dynamics of the domain wall loops by using the moduli approximation and find a phase rotation induces a repulsive force which can be understood as a Noether charge of Q-solitons. Non-Abelian gauge theory allows different types of loops which can be deformed to each other by changing a modulus. This admits the moduli geometry like a sandglass made by gluing the tips of the two cigar-(cone-)like metrics of a single triangle loop. We conclude that the sizes of all loops tend to grow for a late time in general models with complex Higgs masses, while the sizes are stabilized at some values once triplet masses are introduced for the Higgs fields. We also show that the stationary motion on the moduli space of the domain wall webs represents 1/4 Bogomol'nyi-Prasad-Sommerfield Q-webs of walls.

  6. Aversive control: A separate domain?

    PubMed Central

    Hineline, Philip N.

    1984-01-01

    Traditionally, aversive control has been viewed as a separate domain within behavior theory. Sometimes this separateness has been based upon a distinction between reinforcement and punishment, and sometimes upon a distinction between positive and negative reinforcement. The latter is regarded here as the more compelling basis, due to some inherent procedural asymmetries. An approach to the interpretation of negative reinforcement is presented, with indication of types of experiments that support it and that also point to promising directions for further work. However, most of the interpretive issues that arise here are relevant to positively reinforced behavior as well. These include: possible reformulation of the operant/respondent distinction; the place of emotional concepts in behavior analysis; the need for simultaneous, complementary analysis on differing time scales; the understanding of behavioral situations with rewarding or aversive properties that depend as much upon the contingencies that the situations involve as upon the primary rewarding or aversive stimuli that they include. Thus, an adequate understanding of this domain, which has been traditionally viewed as distinct, has implications for all domains of behavior-analytic theory. PMID:16812404

  7. Aversive control: A separate domain?

    PubMed

    Hineline, P N

    1984-11-01

    Traditionally, aversive control has been viewed as a separate domain within behavior theory. Sometimes this separateness has been based upon a distinction between reinforcement and punishment, and sometimes upon a distinction between positive and negative reinforcement. The latter is regarded here as the more compelling basis, due to some inherent procedural asymmetries. An approach to the interpretation of negative reinforcement is presented, with indication of types of experiments that support it and that also point to promising directions for further work. However, most of the interpretive issues that arise here are relevant to positively reinforced behavior as well. These include: possible reformulation of the operant/respondent distinction; the place of emotional concepts in behavior analysis; the need for simultaneous, complementary analysis on differing time scales; the understanding of behavioral situations with rewarding or aversive properties that depend as much upon the contingencies that the situations involve as upon the primary rewarding or aversive stimuli that they include. Thus, an adequate understanding of this domain, which has been traditionally viewed as distinct, has implications for all domains of behavior-analytic theory.

  8. Aversive control: A separate domain?

    PubMed

    Hineline, P N

    1984-11-01

    Traditionally, aversive control has been viewed as a separate domain within behavior theory. Sometimes this separateness has been based upon a distinction between reinforcement and punishment, and sometimes upon a distinction between positive and negative reinforcement. The latter is regarded here as the more compelling basis, due to some inherent procedural asymmetries. An approach to the interpretation of negative reinforcement is presented, with indication of types of experiments that support it and that also point to promising directions for further work. However, most of the interpretive issues that arise here are relevant to positively reinforced behavior as well. These include: possible reformulation of the operant/respondent distinction; the place of emotional concepts in behavior analysis; the need for simultaneous, complementary analysis on differing time scales; the understanding of behavioral situations with rewarding or aversive properties that depend as much upon the contingencies that the situations involve as upon the primary rewarding or aversive stimuli that they include. Thus, an adequate understanding of this domain, which has been traditionally viewed as distinct, has implications for all domains of behavior-analytic theory. PMID:16812404

  9. Generic domain models in software engineering

    NASA Technical Reports Server (NTRS)

    Maiden, Neil

    1992-01-01

    This paper outlines three research directions related to domain-specific software development: (1) reuse of generic models for domain-specific software development; (2) empirical evidence to determine these generic models, namely elicitation of mental knowledge schema possessed by expert software developers; and (3) exploitation of generic domain models to assist modelling of specific applications. It focuses on knowledge acquisition for domain-specific software development, with emphasis on tool support for the most important phases of software development.

  10. Domain wall orientation and domain shape in KTiOPO4 crystals

    NASA Astrophysics Data System (ADS)

    Shur, V. Ya.; Vaskina, E. M.; Pelegova, E. V.; Chuvakova, M. A.; Akhmatkhanov, A. R.; Kizko, O. V.; Ivanov, M.; Kholkin, A. L.

    2016-09-01

    Domain shape evolution and domain wall motion have been studied in KTiOPO4 (KTP) ferroelectric single crystals using complementary experimental methods. The in situ visualization of domain kinetics has allowed revealing: (1) qualitative change of the domain shape, (2) dependence of the domain wall velocity on its orientation, (3) jump-like domain wall motion caused by domain merging, (4) effect of domain shape stability. The model of domain wall motion driven by generation of elementary steps (kink-pair nucleation) and subsequent kink motion is presented. The decrease in the relative velocity of the approaching parallel domain walls is attributed to electrostatic interaction. The effect of polarization reversal induced by chemical etching is observed. The obtained results are important for the development of domain engineering in the crystals of KTP family.

  11. The Promise of Domain Adaptation

    NASA Astrophysics Data System (ADS)

    Mahabal, Ashish A.; Li, Jingling; Vaijanapurkar, Samarth; Bue, Brian; Miller, Adam; Donalek, Ciro; Djorgovski, Stanislav G.; Drake, Andrew J.; Graham, Matthew; CRTS, iPTF

    2016-01-01

    Most new surveys spend an appreciable time in collecting data on which to train classifiers before they can be used on future observations from the same dataset. The result generating phase can start much earlier if the training could incorporate data accumulated from older surveys enhanced with a small set from the new survey. This is exactly what Domain Adaptation (DA) allows us to do. The main idea behind DAs can be summarized thus: if we have two classes of separable objects in some feature space of a Source survey (S), we can define a hyperplane to separate the two types. In a second Target survey (T), for the same features the hyperplane would be inclined differently. DA methods get the mapping between the two hyperplanes using a small fraction of data from the Target (T) survey and can then be used to predict the classes of the remaining majority of data in T. We discuss the parameters that need to be tuned, the difficulties involved, and ways to improve the results. As we move towards bigger, and deeper surveys, being able to use existing labelled information to conduct classification in future surveys will be more cost-effective and promote time efficiency as well. Starting with the light curve data of 50,000 periodic objects from Catalina Real-Time Transient Survey (CRTS), we have applied domain adaptation techniques such as Geodesic Flow Kernel (GFK) with Random forest classifier and Co-training for domain adaptation (CODA) to the CRTS data which has 35,000 points overlapping with Palomar Transient Factory (PTF), and 12,000 with Lincoln Near-Earth Asteroid Research (LINEAR). The results suggest that domain adaptation is an area worth exploring as the knowledge between these surveys is transferable and the approaches to find the mappings between these surveys can be applied to the remaining data as well as for near future surveys such as CRTS-II, Zwicky Transient Facility (ZTF) and the Large Synoptic Survey Telescope (LSST) to name a few at the optical

  12. Pectin Homogalacturonans: Nanostructural Characterization of Methylesterified Domains

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Functionality of pectic hydrocolloids is largely dependent on the two major domains commonly found in their homogalacturonan (HG) regions, i.e., methylester protected domains (MPDs)and non methylesterified domains (NMDs). MPDs can participate in hydrogen bonding and hydrophobic interactions but unli...

  13. Frequency domain photoacoustic and fluorescence microscopy.

    PubMed

    Langer, Gregor; Buchegger, Bianca; Jacak, Jaroslaw; Klar, Thomas A; Berer, Thomas

    2016-07-01

    We report on simultaneous frequency domain optical-resolution photoacoustic and fluorescence microscopy with sub-µm lateral resolution. With the help of a blood smear, we show that photoacoustic and fluorescence images provide complementary information. Furthermore, we compare theoretically predicted signal-to-noise ratios of sinusoidal modulation in frequency domain with pulsed excitation in time domain. PMID:27446698

  14. Frequency domain photoacoustic and fluorescence microscopy.

    PubMed

    Langer, Gregor; Buchegger, Bianca; Jacak, Jaroslaw; Klar, Thomas A; Berer, Thomas

    2016-07-01

    We report on simultaneous frequency domain optical-resolution photoacoustic and fluorescence microscopy with sub-µm lateral resolution. With the help of a blood smear, we show that photoacoustic and fluorescence images provide complementary information. Furthermore, we compare theoretically predicted signal-to-noise ratios of sinusoidal modulation in frequency domain with pulsed excitation in time domain.

  15. Frequency domain photoacoustic and fluorescence microscopy

    PubMed Central

    Langer, Gregor; Buchegger, Bianca; Jacak, Jaroslaw; Klar, Thomas A.; Berer, Thomas

    2016-01-01

    We report on simultaneous frequency domain optical-resolution photoacoustic and fluorescence microscopy with sub-µm lateral resolution. With the help of a blood smear, we show that photoacoustic and fluorescence images provide complementary information. Furthermore, we compare theoretically predicted signal-to-noise ratios of sinusoidal modulation in frequency domain with pulsed excitation in time domain. PMID:27446698

  16. One Health Core Competency Domains.

    PubMed

    Frankson, Rebekah; Hueston, William; Christian, Kira; Olson, Debra; Lee, Mary; Valeri, Linda; Hyatt, Raymond; Annelli, Joseph; Rubin, Carol

    2016-01-01

    The emergence of complex global challenges at the convergence of human, animal, and environmental health has catalyzed a movement supporting "One Health" approaches. Despite recognition of the importance of One Health approaches to address these complex challenges, little effort has been directed at identifying the seminal knowledge, skills, and attitudes necessary for individuals to successfully contribute to One Health efforts. Between 2008 and 2011, three groups independently embarked on separate initiatives to identify core competencies for professionals involved with One Health approaches. Core competencies were considered critically important for guiding curriculum development and continuing professional education, as they describe the knowledge, skills, and attitudes required to be effective. A workshop was convened in 2012 to synthesize the various strands of work on One Health competencies. Despite having different mandates, participants, and approaches, all of these initiatives identified similar core competency domains: management; communication and informatics; values and ethics; leadership; teams and collaboration; roles and responsibilities; and systems thinking. These core competency domains have been used to develop new continuing professional education programs for One Health professionals and help university curricula prepare new graduates to be able to contribute more effectively to One Health approaches. PMID:27679794

  17. One Health Core Competency Domains

    PubMed Central

    Frankson, Rebekah; Hueston, William; Christian, Kira; Olson, Debra; Lee, Mary; Valeri, Linda; Hyatt, Raymond; Annelli, Joseph; Rubin, Carol

    2016-01-01

    The emergence of complex global challenges at the convergence of human, animal, and environmental health has catalyzed a movement supporting “One Health” approaches. Despite recognition of the importance of One Health approaches to address these complex challenges, little effort has been directed at identifying the seminal knowledge, skills, and attitudes necessary for individuals to successfully contribute to One Health efforts. Between 2008 and 2011, three groups independently embarked on separate initiatives to identify core competencies for professionals involved with One Health approaches. Core competencies were considered critically important for guiding curriculum development and continuing professional education, as they describe the knowledge, skills, and attitudes required to be effective. A workshop was convened in 2012 to synthesize the various strands of work on One Health competencies. Despite having different mandates, participants, and approaches, all of these initiatives identified similar core competency domains: management; communication and informatics; values and ethics; leadership; teams and collaboration; roles and responsibilities; and systems thinking. These core competency domains have been used to develop new continuing professional education programs for One Health professionals and help university curricula prepare new graduates to be able to contribute more effectively to One Health approaches. PMID:27679794

  18. One Health Core Competency Domains

    PubMed Central

    Frankson, Rebekah; Hueston, William; Christian, Kira; Olson, Debra; Lee, Mary; Valeri, Linda; Hyatt, Raymond; Annelli, Joseph; Rubin, Carol

    2016-01-01

    The emergence of complex global challenges at the convergence of human, animal, and environmental health has catalyzed a movement supporting “One Health” approaches. Despite recognition of the importance of One Health approaches to address these complex challenges, little effort has been directed at identifying the seminal knowledge, skills, and attitudes necessary for individuals to successfully contribute to One Health efforts. Between 2008 and 2011, three groups independently embarked on separate initiatives to identify core competencies for professionals involved with One Health approaches. Core competencies were considered critically important for guiding curriculum development and continuing professional education, as they describe the knowledge, skills, and attitudes required to be effective. A workshop was convened in 2012 to synthesize the various strands of work on One Health competencies. Despite having different mandates, participants, and approaches, all of these initiatives identified similar core competency domains: management; communication and informatics; values and ethics; leadership; teams and collaboration; roles and responsibilities; and systems thinking. These core competency domains have been used to develop new continuing professional education programs for One Health professionals and help university curricula prepare new graduates to be able to contribute more effectively to One Health approaches.

  19. One Health Core Competency Domains.

    PubMed

    Frankson, Rebekah; Hueston, William; Christian, Kira; Olson, Debra; Lee, Mary; Valeri, Linda; Hyatt, Raymond; Annelli, Joseph; Rubin, Carol

    2016-01-01

    The emergence of complex global challenges at the convergence of human, animal, and environmental health has catalyzed a movement supporting "One Health" approaches. Despite recognition of the importance of One Health approaches to address these complex challenges, little effort has been directed at identifying the seminal knowledge, skills, and attitudes necessary for individuals to successfully contribute to One Health efforts. Between 2008 and 2011, three groups independently embarked on separate initiatives to identify core competencies for professionals involved with One Health approaches. Core competencies were considered critically important for guiding curriculum development and continuing professional education, as they describe the knowledge, skills, and attitudes required to be effective. A workshop was convened in 2012 to synthesize the various strands of work on One Health competencies. Despite having different mandates, participants, and approaches, all of these initiatives identified similar core competency domains: management; communication and informatics; values and ethics; leadership; teams and collaboration; roles and responsibilities; and systems thinking. These core competency domains have been used to develop new continuing professional education programs for One Health professionals and help university curricula prepare new graduates to be able to contribute more effectively to One Health approaches.

  20. Word Domain Disambiguation via Word Sense Disambiguation

    SciTech Connect

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

    2006-06-04

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

  1. GMPLS inter-domain signaling and routing to control LSPs based on per-domain policy

    NASA Astrophysics Data System (ADS)

    Okamoto, S.; Guo, H.; Otani, T.

    2008-11-01

    GMPLS inter-domain network control was investigated by employing BGP-based inter-domain routing and flexible signaling with loose hop expansion. Per-domain based operational policy was successfully applied to the establishment of GMPLS inter-domain LSPs.

  2. Domain adaptive boosting method and its applications

    NASA Astrophysics Data System (ADS)

    Geng, Jie; Miao, Zhenjiang

    2015-03-01

    Differences of data distributions widely exist among datasets, i.e., domains. For many pattern recognition, nature language processing, and content-based analysis systems, a decrease in performance caused by the domain differences between the training and testing datasets is still a notable problem. We propose a domain adaptation method called domain adaptive boosting (DAB). It is based on the AdaBoost approach with extensions to cover the domain differences between the source and target domains. Two main stages are contained in this approach: source-domain clustering and source-domain sample selection. By iteratively adding the selected training samples from the source domain, the discrimination model is able to achieve better domain adaptation performance based on a small validation set. The DAB algorithm is suitable for the domains with large scale samples and easy to extend for multisource adaptation. We implement this method on three computer vision systems: the skin detection model in single images, the video concept detection model, and the object classification model. In the experiments, we compare the performances of several commonly used methods and the proposed DAB. Under most situations, the DAB is superior.

  3. Domain wall conduction in multiaxial ferroelectrics

    SciTech Connect

    Eliseev, E. A.; Morozovska, A. N.; Svechnikov, S. V.; Maksymovych, Petro; Kalinin, Sergei V

    2012-01-01

    The conductance of domain wall structures consisting of either stripes or cylindrical domains in multiaxial ferroelectric-semiconductors is analyzed. The effects of the flexoelectric coupling, domain size, wall tilt, and curvature on charge accumulation are analyzed using the Landau-Ginsburg Devonshire theory for polarization vector combined with the Poisson equation for charge distributions. The proximity and size effect of the electron and donor accumulation/depletion by thin stripe domains and cylindrical nanodomains are revealed. In contrast to thick domain stripes and wider cylindrical domains, in which the carrier accumulation (and so the static conductivity) sharply increases at the domain walls only, small nanodomains of radii less than 5-10 correlation lengths appeared conducting across the entire cross-section. Implications of such conductive nanosized channels may be promising for nanoelectronics.

  4. Morphology and interaction between lipid domains

    PubMed Central

    Ursell, Tristan S.; Klug, William S.; Phillips, Rob

    2009-01-01

    Cellular membranes are a heterogeneous mix of lipids, proteins and small molecules. Special groupings enriched in saturated lipids and cholesterol form liquid-ordered domains, known as “lipid rafts,” thought to serve as platforms for signaling, trafficking and material transport throughout the secretory pathway. Questions remain as to how the cell maintains small fluid lipid domains, through time, on a length scale consistent with the fact that no large-scale phase separation is observed. Motivated by these examples, we have utilized a combination of mechanical modeling and in vitro experiments to show that membrane morphology plays a key role in maintaining small domain sizes and organizing domains in a model membrane. We demonstrate that lipid domains can adopt a flat or dimpled morphology, where the latter facilitates a repulsive interaction that slows coalescence and helps regulate domain size and tends to laterally organize domains in the membrane. PMID:19620730

  5. Functional innovation from changes in protein domains and their combinations.

    PubMed

    Lees, Jonathan G; Dawson, Natalie L; Sillitoe, Ian; Orengo, Christine A

    2016-06-01

    Domains are the functional building blocks of proteins. In this work we discuss how domains can contribute to the evolution of new functions. Domains themselves can evolve through various mechanisms, altering their intrinsic function. Domains can also facilitate functional innovations by combining with other domains to make novel proteins. We discuss the mechanisms by which domain and domain combinations support functional innovations. We highlight interesting examples where changes in domain combination promote changes at the domain level. PMID:27309309

  6. Structure and Function of KH Domains

    SciTech Connect

    Valverde, R.; Regan, E

    2008-01-01

    The hnRNP K homology (KH) domain was first identified in the protein human heterogeneous nuclear ribonucleoprotein K (hnRNP K) 14 years ago. Since then, KH domains have been identified as nucleic acid recognition motifs in proteins that perform a wide range of cellular functions. KH domains bind RNA or ssDNA, and are found in proteins associated with transcriptional and translational regulation, along with other cellular processes. Several diseases, e.g. fragile X mental retardation syndrome and paraneoplastic disease, are associated with the loss of function of a particular KH domain. Here we discuss the progress made towards understanding both general and specific features of the molecular recognition of nucleic acids by KH domains. The typical binding surface of KH domains is a cleft that is versatile but that can typically accommodate only four unpaired bases. Van der Waals forces and hydrophobic interactions and, to a lesser extent, electrostatic interactions, contribute to the nucleic acid binding affinity. 'Augmented' KH domains or multiple copies of KH domains within a protein are two strategies that are used to achieve greater affinity and specificity of nucleic acid binding. Isolated KH domains have been seen to crystallize as monomers, dimers and tetramers, but no published data support the formation of noncovalent higher-order oligomers by KH domains in solution. Much attention has been given in the literature to a conserved hydrophobic residue (typically Ile or Leu) that is present in most KH domains. The interest derives from the observation that an individual with this Ile mutated to Asn, in the KH2 domain of fragile X mental retardation protein, exhibits a particularly severe form of the syndrome. The structural effects of this mutation in the fragile X mental retardation protein KH2 domain have recently been reported. We discuss the use of analogous point mutations at this position in other KH domains to dissect both structure and function.

  7. Structural basis for the phosphorylation-regulated interaction between the cytoplasmic tail of cell polarity protein crumbs and the actin-binding protein moesin.

    PubMed

    Wei, Zhiyi; Li, Youjun; Ye, Fei; Zhang, Mingjie

    2015-05-01

    The type I transmembrane protein crumbs (Crb) plays critical roles in the establishment and maintenance of cell polarities in diverse tissues. As such, mutations of Crb can cause different forms of cancers. The cell intrinsic role of Crb in cell polarity is governed by its conserved, 37-residue cytoplasmic tail (Crb-CT) via binding to moesin and protein associated with Lin7-1 (PALS1). However, the detailed mechanism governing the Crb·moesin interaction and the balance of Crb in binding to moesin and PALS1 are not well understood. Here we report the 1.5 Å resolution crystal structure of the moesin protein 4.1/ezrin/radixin/moesin (FERM)·Crb-CT complex, revealing that both the canonical FERM binding motif and the postsynaptic density protein-95/Disc large-1/Zonula occludens-1 (PDZ) binding motif of Crb contribute to the Crb·moesin interaction. We further demonstrate that phosphorylation of Crb-CT by atypical protein kinase C (aPKC) disrupts the Crb·moesin association but has no impact on the Crb·PALS1 interaction. The above results indicate that, upon the establishment of the apical-basal polarity in epithelia, apical-localized aPKC can actively prevent the Crb·moesin complex formation and thereby shift Crb to form complex with PALS1 at apical junctions. Therefore, Crb may serve as an aPKC-mediated sensor in coordinating contact-dependent cell growth inhibition in epithelial tissues.

  8. EuPathDomains: the divergent domain database for eukaryotic pathogens.

    PubMed

    Ghouila, Amel; Terrapon, Nicolas; Gascuel, Olivier; Guerfali, Fatma Z; Laouini, Dhafer; Maréchal, Eric; Bréhélin, Laurent

    2011-06-01

    Eukaryotic pathogens (e.g. Plasmodium, Leishmania, Trypanosomes, etc.) are a major source of morbidity and mortality worldwide. In Africa, one of the most impacted continents, they cause millions of deaths and constitute an immense economic burden. While the genome sequence of several of these organisms is now available, the biological functions of more than half of their proteins are still unknown. This is a serious issue for bringing to the foreground the expected new therapeutic targets. In this context, the identification of protein domains is a key step to improve the functional annotation of the proteins. However, several domains are missed in eukaryotic pathogens because of the high phylogenetic distance of these organisms from the classical eukaryote models. We recently proposed a method, co-occurrence domain detection (CODD), that improves the sensitivity of Pfam domain detection by exploiting the tendency of domains to appear preferentially with a few other favorite domains in a protein. In this paper, we present EuPathDomains (http://www.atgc-montpellier.fr/EuPathDomains/), an extended database of protein domains belonging to ten major eukaryotic human pathogens. EuPathDomains gathers known and new domains detected by CODD, along with the associated confidence measurements and the GO annotations that can be deduced from the new domains. This database significantly extends the Pfam domain coverage of all selected genomes, by proposing new occurrences of domains as well as new domain families that have never been reported before. For example, with a false discovery rate lower than 20%, EuPathDomains increases the number of detected domains by 13% in Toxoplasma gondii genome and up to 28% in Cryptospordium parvum, and the total number of domain families by 10% in Plasmodium falciparum and up to 16% in C. parvum genome. The database can be queried by protein names, domain identifiers, Pfam or Interpro identifiers, or organisms, and should become a valuable

  9. Imaging Ferroelectric Domains and Domain Walls Using Charge Gradient Microscopy: Role of Screening Charges.

    PubMed

    Tong, Sheng; Jung, Il Woong; Choi, Yoon-Young; Hong, Seungbum; Roelofs, Andreas

    2016-02-23

    Advanced scanning probe microscopies (SPMs) open up the possibilities of the next-generation ferroic devices that utilize both domains and domain walls as active elements. However, current SPMs lack the capability of dynamically monitoring the motion of domains and domain walls in conjunction with the transport of the screening charges that lower the total electrostatic energy of both domains and domain walls. Charge gradient microscopy (CGM) is a strong candidate to overcome these shortcomings because it can map domains and domain walls at high speed and mechanically remove the screening charges. Yet the underlying mechanism of the CGM signals is not fully understood due to the complexity of the electrostatic interactions. Here, we designed a semiconductor-metal CGM tip, which can separate and quantify the ferroelectric domain and domain wall signals by simply changing its scanning direction. Our investigation reveals that the domain wall signals are due to the spatial change of polarization charges, while the domain signals are due to continuous removal and supply of screening charges at the CGM tip. In addition, we observed asymmetric CGM domain currents from the up and down domains, which are originated from the different debonding energies and the amount of the screening charges on positive and negative bound charges. We believe that our findings can help design CGM with high spatial resolution and lead to breakthroughs in information storage and energy-harvesting devices. PMID:26751281

  10. Is the myonuclear domain size fixed?

    PubMed

    Van der Meer, S F T; Jaspers, R T; Degens, H

    2011-12-01

    It has been suggested that the number of myonuclei in a muscle fibre changes in proportion to the change in fibre size, resulting in a constant myonuclear domain size, defined as the cytoplasmic volume per myonucleus. The myonuclear domain size varies, however, between fibre types and is inversely related with the oxidative capacity of a fibre. Overall, the observations of an increase in myonuclear domain size during both maturational growth and overload-induced hypertrophy, and the decrease in myonuclear domain size during disuse- and ageing-associated muscle atrophy suggest that the concept of a constant myonuclear domain size needs to be treated cautiously. It also suggests that only when the myonuclear domain size exceeds a certain threshold during growth or overload-induced hypertrophy acquisition of new myonuclei is required for further fibre hypertrophy. PMID:22130137

  11. Pattern orientation in finite domains without boundaries

    NASA Astrophysics Data System (ADS)

    Rapp, Lisa; Bergmann, Fabian; Zimmermann, Walter

    2016-01-01

    We investigate the orientation of nonlinear stripe patterns in finite domains. Motivated by recent experiments, we introduce a control parameter drop from supercritical inside a domain to subcritical outside without boundary conditions at the domain border. As a result, stripes align perpendicularly to shallow control parameter drops. For steeper drops, non-adiabatic effects lead to a surprising orientational transition to parallel stripes with respect to the borders. We demonstrate this effect in terms of the Brusselator model and generic amplitude equations.

  12. Domain decomposition for the SPN solver MINOS

    SciTech Connect

    Jamelot, Erell; Baudron, Anne-Marie; Lautard, Jean-Jacques

    2012-07-01

    In this article we present a domain decomposition method for the mixed SPN equations, discretized with Raviart-Thomas-Nedelec finite elements. This domain decomposition is based on the iterative Schwarz algorithm with Robin interface conditions to handle communications. After having described this method, we give details on how to optimize the convergence. Finally, we give some numerical results computed in a realistic 3D domain. The computations are done with the MINOS solver of the APOLLO3 (R) code. (authors)

  13. Domain Transfer Learning for MCI Conversion Prediction.

    PubMed

    Cheng, Bo; Liu, Mingxia; Zhang, Daoqiang; Munsell, Brent C; Shen, Dinggang

    2015-07-01

    Machine learning methods have successfully been used to predict the conversion of mild cognitive impairment (MCI) to Alzheimer's disease (AD), by classifying MCI converters (MCI-C) from MCI nonconverters (MCI-NC). However, most existing methods construct classifiers using data from one particular target domain (e.g., MCI), and ignore data in other related domains (e.g., AD and normal control (NC)) that may provide valuable information to improve MCI conversion prediction performance. To address is limitation, we develop a novel domain transfer learning method for MCI conversion prediction, which can use data from both the target domain (i.e., MCI) and auxiliary domains (i.e., AD and NC). Specifically, the proposed method consists of three key components: 1) a domain transfer feature selection component that selects the most informative feature-subset from both target domain and auxiliary domains from different imaging modalities; 2) a domain transfer sample selection component that selects the most informative sample-subset from the same target and auxiliary domains from different data modalities; and 3) a domain transfer support vector machine classification component that fuses the selected features and samples to separate MCI-C and MCI-NC patients. We evaluate our method on 202 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) that have MRI, FDG-PET, and CSF data. The experimental results show the proposed method can classify MCI-C patients from MCI-NC patients with an accuracy of 79.4%, with the aid of additional domain knowledge learned from AD and NC.

  14. Frequency domain FIR and IIR adaptive filters

    NASA Technical Reports Server (NTRS)

    Lynn, D. W.

    1990-01-01

    A discussion of the LMS adaptive filter relating to its convergence characteristics and the problems associated with disparate eigenvalues is presented. This is used to introduce the concept of proportional convergence. An approach is used to analyze the convergence characteristics of block frequency-domain adaptive filters. This leads to a development showing how the frequency-domain FIR adaptive filter is easily modified to provide proportional convergence. These ideas are extended to a block frequency-domain IIR adaptive filter and the idea of proportional convergence is applied. Experimental results illustrating proportional convergence in both FIR and IIR frequency-domain block adaptive filters is presented.

  15. Distinction of magnetic non-ferroelastic domains.

    PubMed

    Litvin, D B; Janovec, V

    2006-03-01

    It is shown that there always exists a coordinate system in which components of property tensors that distinguish between the domains of a magnetic non-ferroelastic domain pair differ solely in the two domains by a change in sign. The 309 classes of twin laws of magnetic non-ferroelastic domain pairs are listed and the twin laws, which are given in a coordinate system where the tensor distinction is provided by a change in sign of tensor components, are specified. If the twin law is not given in such a coordinate system, then a new coordinate system, related by a rotation, is specified. PMID:16489246

  16. Transform domain steganography with blind source separation

    NASA Astrophysics Data System (ADS)

    Jouny, Ismail

    2015-05-01

    This paper applies blind source separation or independent component analysis for images that may contain mixtures of text, audio, or other images for steganography purposes. The paper focuses on separating mixtures in the transform domain such as Fourier domain or the Wavelet domain. The study addresses the effectiveness of steganography when using linear mixtures of multimedia components and the ability of standard blind sources separation techniques to discern hidden multimedia messages. Mixing in the space, frequency, and wavelet (scale) domains is compared. Effectiveness is measured using mean square error rate between original and recovered images.

  17. Bioconvection in spatially extended domains

    NASA Astrophysics Data System (ADS)

    Karimi, A.; Paul, M. R.

    2013-05-01

    We numerically explore gyrotactic bioconvection in large spatially extended domains of finite depth using parameter values from available experiments with the unicellular alga Chlamydomonas nivalis. We numerically integrate the three-dimensional, time-dependent continuum model of Pedley [J. Fluid Mech.10.1017/S0022112088002393 195, 223 (1988)] using a high-order, parallel, spectral-element approach. We explore the long-time nonlinear patterns and dynamics found for layers with an aspect ratio of 10 over a range of Rayleigh numbers. Our results yield the pattern wavelength and pattern dynamics which we compare with available theory and experimental measurement. There is good agreement for the pattern wavelength at short times between numerics, experiment, and a linear stability analysis. At long times we find that the general sequence of patterns given by the nonlinear evolution of the governing equations correspond qualitatively to what has been described experimentally. However, at long times the patterns in numerics grow to larger wavelengths, in contrast to what is observed in experiment where the wavelength is found to decrease with time.

  18. Optical coherence domain reflectometry guidewire

    DOEpatents

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

    2001-01-01

    A guidewire with optical sensing capabilities is based on a multiplexed optical coherence domain reflectometer (OCDR), which allows it to sense location, thickness, and structure of the arterial walls or other intra-cavity regions as it travels through the body during minimally invasive medical procedures. This information will be used both to direct the guidewire through the body by detecting vascular junctions and to evaluate the nearby tissue. The guidewire contains multiple optical fibers which couple light from the proximal to distal end. Light from the fibers at the distal end of the guidewire is directed onto interior cavity walls via small diameter optics such as gradient index lenses and mirrored corner cubes. Both forward viewing and side viewing fibers can be included. The light reflected or scattered from the cavity walls is then collected by the fibers, which are multiplexed at the proximal end to the sample arm of an optical low coherence reflectometer. The guidewire can also be used in nonmedical applications.

  19. Time Domain Challenges for Exoplanets

    NASA Astrophysics Data System (ADS)

    Dawson, Rebekah Ilene

    2016-01-01

    Over the past couple decades, thousands of extra-solar planets have been discovered orbiting other stars. Most have been detected and characterized using transit and/or radial velocity time series, and these techniques have undergone huge improvements in instrumental precision. However, the improvements in precision have brought to light new statistical challenges in detecting and characterizing exoplanets in the presence of correlated noise caused by stellar activity (transits and radial velocities) and gaps in the time sampling (radial velocities). These challenges have afflicted many of the most interesting exoplanets, from Earth-like planets to planetary systems whose orbital dynamics place important constraints on how planetary systems form and evolve. In the first part of the talk, I will focus on the problem of correlated noise for characterizing transiting exoplanets using transit timing variations. I will present a comparison of several techniques using wavelets, Gaussian processes, and polynomial splines to account for correlated noise in the likelihood function when inferring planetary parameters. I will also present results on the characteristics of correlated noise that cause planets to be missed by the Kepler and homegrown pipelines despite high nominal signal-to-noise. In the second part of the talk, I will focus on the problem of aliasing caused by gaps in the radial-velocity time series on yearly, daily, and monthly timescales. I will present results on identifying aliases in the Fourier domain by taking advantage of aliasing on multiple timescales and discuss the interplay between aliasing and stellar activity for several habitable-zone "planets" that have recently been called into question as possible spurious signals caused by activity. As we push toward detecting and characterizing lower mass planets, it is essential that astrostatistical advances keep pace with advances in instrumentation.

  20. Are Epistemological Beliefs Similar across Domains?

    ERIC Educational Resources Information Center

    Schommer, Marlene; Walker, Kiersten

    1995-01-01

    College students in 2 studies (n=95 and 114) completed an epistemological questionnaire with a specific domain in mind (social sciences or mathematics), read a passage, answered a passage test, and completed another epistemological questionnaire. Results supported the idea that individuals' epistemological beliefs tended to be domain independent.…

  1. Domain transfer learning for MCI conversion prediction.

    PubMed

    Cheng, Bo; Zhang, Daoqiang; Shen, Dinggang

    2012-01-01

    In recent studies of Alzheimer's disease (AD), it has increasing attentions in identifying mild cognitive impairment (MCI) converters (MCI-C) from MCI non-converters (MCI-NC). Note that MCI is a prodromal stage of AD, with possibility to convert to AD. Most traditional methods for MCI conversion prediction learn information only from MCI subjects (including MCI-C and MCI-NC), not from other related subjects, e.g., AD and normal controls (NC), which can actually aid the classification between MCI-C and MCI-NC. In this paper, we propose a novel domain-transfer learning method for MCI conversion prediction. Different from most existing methods, we classify MCI-C and MCI-NC with aid from the domain knowledge learned with AD and NC subjects as auxiliary domain to further improve the classification performance. Our method contains two key components: (1) the cross-domain kernel learning for transferring auxiliary domain knowledge, and (2) the adapted support vector machine (SVM) decision function construction for cross-domain and auxiliary domain knowledge fusion. Experimental results on the Alzheimer's Disease neuroimaging initiative (ADNI) database show that the proposed method can significantly improve the classification performance between MCI-C and MCI-NC, with aid of domain knowledge learned from AD and NC subjects.

  2. Domains of the Florida Performance Measurement System.

    ERIC Educational Resources Information Center

    Florida State Dept. of Education, Tallahassee.

    This monograph sets forth in detail the concepts included in the five domains of teaching as identified by the Florida Coalition for the Development of a Performance Evaluation System. The first domain, planning, includes the concepts: (1) content coverage; (2) utilization of instructional materials; (3) activity structure; (4) goal focusing; and…

  3. The Domain Specificity of Academic Emotional Experiences

    ERIC Educational Resources Information Center

    Goetz, Thomas; Frenzel, Anne C.; Pekrun, Reinhard; Hall, Nathan C.

    2006-01-01

    The authors analyzed the domain specificity of emotions and focused on experiences of enjoyment, anxiety, and boredom in the domains of mathematics, Latin, German, and English. On the basis of assumptions in R. Pekrun's (2000; in press) control-value theory and findings of pilot studies, the authors hypothesized the existence of a largely…

  4. Student Behavior and Attitudes: The Affective Domain.

    ERIC Educational Resources Information Center

    Archer, Patricia F.

    This two-part learning module, designed to acquaint teachers with the affective domain of Bloom's Taxonomy, provides a methodology for identifying the attitudinal and motivational problems of non-traditional students. Part I discusses the cognitive, affective, and psychomotor domains considered in Bloom's Taxonomy and presents possible learning…

  5. Multiple hypothesis tracking for the cyber domain

    NASA Astrophysics Data System (ADS)

    Schwoegler, Stefan; Blackman, Sam; Holsopple, Jared; Hirsch, Michael J.

    2011-09-01

    This paper discusses how methods used for conventional multiple hypothesis tracking (MHT) can be extended to domain-agnostic tracking of entities from non-kinematic constraints such as those imposed by cyber attacks in a potentially dense false alarm background. MHT is widely recognized as the premier method to avoid corrupting tracks with spurious data in the kinematic domain but it has not been extensively applied to other problem domains. The traditional approach is to tightly couple track maintenance (prediction, gating, filtering, probabilistic pruning, and target confirmation) with hypothesis management (clustering, incompatibility maintenance, hypothesis formation, and Nassociation pruning). However, by separating the domain specific track maintenance portion from the domain agnostic hypothesis management piece, we can begin to apply the wealth of knowledge gained from ground and air tracking solutions to the cyber (and other) domains. These realizations led to the creation of Raytheon's Multiple Hypothesis Extensible Tracking Architecture (MHETA). In this paper, we showcase MHETA for the cyber domain, plugging in a well established method, CUBRC's INFormation Engine for Real-time Decision making, (INFERD), for the association portion of the MHT. The result is a CyberMHT. We demonstrate the power of MHETA-INFERD using simulated data. Using metrics from both the tracking and cyber domains, we show that while no tracker is perfect, by applying MHETA-INFERD, advanced nonkinematic tracks can be captured in an automated way, perform better than non-MHT approaches, and decrease analyst response time to cyber threats.

  6. 22 CFR 120.11 - Public domain.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Public domain. (a) Public domain means information which is published and which is generally accessible... published information; (3) Through second class mailing privileges granted by the U.S. Government; (4) At libraries open to the public or from which the public can obtain documents; (5) Through patents available...

  7. 22 CFR 120.11 - Public domain.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Public domain. (a) Public domain means information which is published and which is generally accessible... published information; (3) Through second class mailing privileges granted by the U.S. Government; (4) At libraries open to the public or from which the public can obtain documents; (5) Through patents available...

  8. 22 CFR 120.11 - Public domain.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Public domain. (a) Public domain means information which is published and which is generally accessible... published information; (3) Through second class mailing privileges granted by the U.S. Government; (4) At libraries open to the public or from which the public can obtain documents; (5) Through patents available...

  9. XML Based Markup Languages for Specific Domains

    NASA Astrophysics Data System (ADS)

    Varde, Aparna; Rundensteiner, Elke; Fahrenholz, Sally

    A challenging area in web based support systems is the study of human activities in connection with the web, especially with reference to certain domains. This includes capturing human reasoning in information retrieval, facilitating the exchange of domain-specific knowledge through a common platform and developing tools for the analysis of data on the web from a domain expert's angle. Among the techniques and standards related to such work, we have XML, the eXtensible Markup Language. This serves as a medium of communication for storing and publishing textual, numeric and other forms of data seamlessly. XML tag sets are such that they preserve semantics and simplify the understanding of stored information by users. Often domain-specific markup languages are designed using XML, with a user-centric perspective. Standardization bodies and research communities may extend these to include additional semantics of areas within and related to the domain. This chapter outlines the issues to be considered in developing domain-specific markup languages: the motivation for development, the semantic considerations, the syntactic constraints and other relevant aspects, especially taking into account human factors. Illustrating examples are provided from domains such as Medicine, Finance and Materials Science. Particular emphasis in these examples is on the Materials Markup Language MatML and the semantics of one of its areas, namely, the Heat Treating of Materials. The focus of this chapter, however, is not the design of one particular language but rather the generic issues concerning the development of domain-specific markup languages.

  10. Actin-organising properties of the muscular dystrophy protein myotilin.

    PubMed

    von Nandelstadh, Pernilla; Grönholm, Mikaela; Moza, Monica; Lamberg, Arja; Savilahti, Harri; Carpén, Olli

    2005-10-15

    Myotilin is a sarcomeric Z-disc protein that binds F-actin directly and bundles actin filaments, although it does not contain a conventional actin-binding domain. Expression of mutant myotilin leads to sarcomeric alterations in the dominantly inherited limb-girdle muscular dystrophy 1A and in myofibrillar myopathy/desmin-related myopathy. Together, with previous in vitro studies, this indicates that myotilin has an important function in the assembly and maintenance of Z-discs. This study characterises further the interaction between myotilin and actin. Functionally important regions in myotilin were identified by actin pull-down and yeast two-hybrid assays and with a novel strategy that combines in vitro DNA transposition-based peptide insertion mutagenesis with phenotype analysis in yeast cells. The shortest fragment to bind actin was the second Ig domain together with a short C-terminal sequence. Concerted action of the first and second Ig domain was, however, necessary for the functional activity of myotilin, as verified by analysis of transposon mutants, actin binding and phenotypic effect in mammalian cells. Furthermore, the Ig domains flanked with N- and C-terminal regions were needed for actin-bundling, indicating that the mere actin-binding sequence was insufficient for the actin-regulating activity. None of the four known disease-associated mutations altered the actin-organising ability. These results, together with previous studies in titin and kettin, identify the Ig domain as an actin-binding unit.

  11. Thermodynamics of heme-induced conformational changes in hemopexin: role of domain-domain interactions.

    PubMed Central

    Wu, M. L.; Morgan, W. T.

    1995-01-01

    Hemopexin is a serum glycoprotein that binds heme with high affinity and delivers heme to the liver cells via receptor-mediated endocytosis. A hinge region connects the two non-disulfide-linked domains of hemopexin, a 35-kDa N-terminal domain (domain I) that binds heme, and a 25-kDa C-terminal domain (domain II). Although domain II does not bind heme, it assumes one structural state in apo-hemopexin and another in heme-hemopexin, and this change is important in facilitating the association of heme-hemopexin with its receptor. In order to elucidate the structure and function of hemopexin, it is important to understand how structural information is transmitted to domain II when domain I binds heme. Here we report a study of the protein-protein interactions between domain I and domain II using analytical ultracentrifugation and isothermal titration calorimetry. Sedimentation equilibrium analysis showed that domain I associates with domain II both in the presence and absence of heme with Kd values of 0.8 microM and 55 microM, respectively. The interaction between heme-domain I and domain II has a calorimetric enthalpy of +11 kcal/mol, a heat capacity (delta Cp) of -720 cal/mol.K, and a calculated entropy of +65 cal/mol.K. By varying the temperature of the centrifugation equilibrium runs, a van't Hoff plot with an apparent change in enthalpy (delta H) of -3.6 kcal/mol and change in entropy (delta S) of +8.1 cal/mol.K for the association of apo-domain I with domain II was obtained.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7773173

  12. Nonequilibrium Raftlike Membrane Domains under Continuous Recycling

    NASA Astrophysics Data System (ADS)

    Turner, Matthew S.; Sens, Pierre; Socci, Nicholas D.

    2005-10-01

    We present a model for the kinetics of spontaneous membrane domain (raft) assembly that includes the effect of membrane recycling ubiquitous in living cells. We show that domains can have a broad power-law distribution with an average radius that scales with the 1/4 power of the domain lifetime when the line tension at the domain edges is large. For biologically reasonable recycling and diffusion rates, the average domain radius is in the tens of nm range, consistent with observations. This represents one possible link between signaling (involving rafts) and traffic (recycling) in cells. Finally, we present evidence that suggests that the average raft size may be the same for all scale-free recycling schemes.

  13. Investigation of multilayer magnetic domain lattice file

    NASA Technical Reports Server (NTRS)

    Torok, E. J.; Kamin, M.; Tolman, C. H.

    1980-01-01

    The feasibility of the self structured multilayered bubble domain memory as a mass memory medium for satellite applications is examined. Theoretical considerations of multilayer bubble supporting materials are presented, in addition to the experimental evaluation of current accessed circuitry for various memory functions. The design, fabrication, and test of four device designs is described, and a recommended memory storage area configuration is presented. Memory functions which were demonstrated include the current accessed propagation of bubble domains and stripe domains, pinning of stripe domain ends, generation of single and double bubbles, generation of arrays of coexisting strip and bubble domains in a single garnet layer, and demonstration of different values of the strip out field for single and double bubbles indicating adequate margins for data detection. All functions necessary to develop a multilayer self structured bubble memory device were demonstrated in individual experiments.

  14. The SH2 domain interaction landscape

    PubMed Central

    Tinti, Michele; Kiemer, Lars; Costa, Stefano; Miller, Martin; Sacco, Francesca; Olsen, Jesper V.; Carducci, Martina; Paoluzi, Serena; Langone, Francesca; Workman, Christopher T.; Blom, Nikolaj; Machida, Kazuya; Thompson, Christopher M.; Schutkowski, Mike; Brunak, Søren; Mann, Matthias; Mayer, Bruce J.; Castagnoli, Luisa; Cesareni, Gianni

    2014-01-01

    Summary Members of the SH2 domain family modulate signal transduction by binding to short peptides containing phosphorylated tyrosines. Each domain displays a distinct preference for the sequence context of the phosphorylated residue. We have developed a new high-density peptide chip technology that allows probing the affinity of most SH2 domains for a large fraction of the entire complement of tyrosine phosphopeptides in the human proteome. Using this technique we have experimentally identified thousands of putative SH2- peptide interactions for more than 70 different SH2 domains. By integrating this rich data set with orthogonal context-specific information, we have assembled an SH2 mediated probabilistic interaction network, which we make available as a community resource in the PepSpotDB database. A new predicted dynamic interaction between the SH2 domains of the tyrosine phosphatase SHP2 and the phosphorylated tyrosine in the ERK activation loop was validated by experiments in living cells. PMID:23545499

  15. The SH2 domain interaction landscape.

    PubMed

    Tinti, Michele; Kiemer, Lars; Costa, Stefano; Miller, Martin L; Sacco, Francesca; Olsen, Jesper V; Carducci, Martina; Paoluzi, Serena; Langone, Francesca; Workman, Christopher T; Blom, Nikolaj; Machida, Kazuya; Thompson, Christopher M; Schutkowski, Mike; Brunak, Søren; Mann, Matthias; Mayer, Bruce J; Castagnoli, Luisa; Cesareni, Gianni

    2013-04-25

    Members of the SH2 domain family modulate signal transduction by binding to short peptides containing phosphorylated tyrosines. Each domain displays a distinct preference for the sequence context of the phosphorylated residue. We have developed a high-density peptide chip technology that allows for probing of the affinity of most SH2 domains for a large fraction of the entire complement of tyrosine phosphopeptides in the human proteome. Using this technique, we have experimentally identified thousands of putative SH2-peptide interactions for more than 70 different SH2 domains. By integrating this rich data set with orthogonal context-specific information, we have assembled an SH2-mediated probabilistic interaction network, which we make available as a community resource in the PepspotDB database. A predicted dynamic interaction between the SH2 domains of the tyrosine phosphatase SHP2 and the phosphorylated tyrosine in the extracellular signal-regulated kinase activation loop was validated by experiments in living cells.

  16. Requirements analysis, domain knowledge, and design

    NASA Technical Reports Server (NTRS)

    Potts, Colin

    1988-01-01

    Two improvements to current requirements analysis practices are suggested: domain modeling, and the systematic application of analysis heuristics. Domain modeling is the representation of relevant application knowledge prior to requirements specification. Artificial intelligence techniques may eventually be applicable for domain modeling. In the short term, however, restricted domain modeling techniques, such as that in JSD, will still be of practical benefit. Analysis heuristics are standard patterns of reasoning about the requirements. They usually generate questions of clarification or issues relating to completeness. Analysis heuristics can be represented and therefore systematically applied in an issue-based framework. This is illustrated by an issue-based analysis of JSD's domain modeling and functional specification heuristics. They are discussed in the context of the preliminary design of simple embedded systems.

  17. Using ontology for domain specific information retrieval

    NASA Astrophysics Data System (ADS)

    Shashirekha, H. L.; Murali, S.; Nagabhushan, P.

    2010-02-01

    This paper presents a system for retrieving information from a domain specific document collection made up of data rich unnatural language text documents. Instead of conventional keyword based retrieval, our system makes use of domain ontology to retrieve the information from a collection of documents. The system addresses the problem of representing unnatural language text documents and constructing a classifier model that helps in the efficient retrieval of relevant information. Query to this system may be either the key phrases in terms of concepts or a domain specific unnatural language text document. The classifier used in this system can also be used to assign multiple labels to the previously unseen text document belonging to the same domain. An empirical evaluation of the system is conducted on the domain of text documents describing the classified matrimonial advertisements to determine its performance.

  18. A domain dictionary of trimeric autotransporter adhesins.

    PubMed

    Bassler, Jens; Hernandez Alvarez, Birte; Hartmann, Marcus D; Lupas, Andrei N

    2015-02-01

    Trimeric autotransporter adhesins (TAAs) are modular, highly repetitive outer membrane proteins that mediate adhesion to external surfaces in many Gram-negative bacteria. In recent years, several TAAs have been investigated in considerable detail, also at the structural level. However, in their vast majority, putative TAAs in prokaryotic genomes remain poorly annotated, due to their sequence diversity and changeable domain architecture. In order to achieve an automated annotation of these proteins that is both detailed and accurate we have taken a domain dictionary approach, in which we identify recurrent domains by sequence comparisons, produce bioinformatic descriptors for each domain type, and connect these to structural information where available. We implemented this approach in a web-based platform, daTAA, in 2008 and demonstrated its applicability by reconstructing the complete fiber structure of a TAA conserved in enterobacteria. Here we review current knowledge on the domain structure of TAAs.

  19. Contribution of the CR domain to P-selectin lectin domain allostery by regulating the orientation of the EGF domain.

    PubMed

    Lü, Shouqin; Chen, Shenbao; Mao, Debin; Zhang, Yan; Long, Mian

    2015-01-01

    The allostery of P-selectin has been studied extensively with a focus on the Lec and EGF domains, whereas the contribution of the CR domain remains unclear. Here, molecular dynamics simulations (MDS) combined with homology modeling were preformed to investigate the impact of the CR domain on P-selectin allostery. The results indicated that the CR domain plays a role in the allosteric dynamics of P-selectin in two ways. First, the CR1 domain tends to stabilize the low affinity of P-selectin during the equilibration processes with the transition inhibition from the S1 to S1' state by restraining the extension of the bent EGF orientation, or with the relaxation acceleration of the S2 state by promoting the bending of the extended EGF orientation. Second, the existence of CR domain increases intramolecular extension prior to complex separation, increasing the time available for the allosteric shift during forced dissociation with a prolonged bond duration. These findings further our understanding of the structure-function relationship of P-selectin with the enriched micro-structural bases of the CR domain.

  20. Dzyaloshinskii-Moriya Domain Walls in Nanotubes

    NASA Astrophysics Data System (ADS)

    Tretiakov, Oleg; Goussev, Arseni; Robbins, J. M.; Slastikov, Valeriy

    2015-03-01

    We study domain walls in thin ferromagnetic nanotubes with Dzyaloshinskii-Moriya interaction (DMI). Dramatic effects arise from the interplay of space curvature and spin-orbit induced DMI on the domain wall structure in these systems. The domain walls become narrower in systems with DMI and curvature. Moreover, the domain walls created in such nanotubes can propagate without Walker breakdown for arbitrary applied currents, thus allowing for a robust and controlled domain-wall motion. The domain-wall velocity is directly proportional to the non-adiabatic spin transfer torque current term and is insensitive to the adiabatic current term. Application of an external magnetic field along the nanotube axis triggers rich dynamical response of the curved domain wall. In particular, we show that the propagation velocity is a non-linear function of both the applied field and DMI, and strongly depends on the orientation and chirality of the wall. We acknowledge support by the Grants-in-Aid for Scientific Research (No. 25800184 and No. 25247056) from the MEXT, Japan and SpinNet.

  1. PDEs in Moving Time Dependent Domains

    NASA Astrophysics Data System (ADS)

    Cortez, F.; Rodríguez-Bernal, A.

    In this work we study partial differential equations defined in a domain that moves in time according to the flow of a given ordinary differential equation, starting out of a given initial domain. We first derive a formulation for a particular case of partial differential equations known as balance equations. For this kind of equations we find the equivalent partial differential equations in the initial domain and later we study some particular cases with and without diffusion. We also analyze general second order differential equations, not necessarily of balance type. The equations without diffusion are solved using the characteristics method. We also prove that the diffusion equations, endowed with Dirichlet boundary conditions and initial data, are well posed in the moving domain. For this we show that the principal part of the equivalent equation in the initial domain is uniformly elliptic. We then prove a version of the weak maximum principle for an equation in a moving domain. Finally we perform suitable energy estimates in the moving domain and give sufficient conditions for the solution to converge to zero as time goes to infinity.

  2. J domain independent functions of J proteins.

    PubMed

    Ajit Tamadaddi, Chetana; Sahi, Chandan

    2016-07-01

    Heat shock proteins of 40 kDa (Hsp40s), also called J proteins, are obligate partners of Hsp70s. Via their highly conserved and functionally critical J domain, J proteins interact and modulate the activity of their Hsp70 partners. Mutations in the critical residues in the J domain often result in the null phenotype for the J protein in question. However, as more J proteins have been characterized, it is becoming increasingly clear that a significant number of J proteins do not "completely" rely on their J domains to carry out their cellular functions, as previously thought. In some cases, regions outside the highly conserved J domain have become more important making the J domain dispensable for some, if not for all functions of a J protein. This has profound effects on the evolution of such J proteins. Here we present selected examples of J proteins that perform J domain independent functions and discuss this in the context of evolution of J proteins with dispensable J domains and J-like proteins in eukaryotes.

  3. Benchmark Generation using Domain Specific Modeling

    SciTech Connect

    Bui, Ngoc B.; Zhu, Liming; Gorton, Ian; Liu, Yan

    2007-08-01

    Performance benchmarks are domain specific applications that are specialized to a certain set of technologies and platforms. The development of a benchmark application requires mapping the performance specific domain concepts to an implementation and producing complex technology and platform specific code. Domain Specific Modeling (DSM) promises to bridge the gap between application domains and implementations by allowing designers to specify solutions in domain-specific abstractions and semantics through Domain Specific Languages (DSL). This allows generation of a final implementation automatically from high level models. The modeling and task automation benefits obtained from this approach usually justify the upfront cost involved. This paper employs a DSM based approach to invent a new DSL, DSLBench, for benchmark generation. DSLBench and its associated code generation facilities allow the design and generation of a completely deployable benchmark application for performance testing from a high level model. DSLBench is implemented using Microsoft Domain Specific Language toolkit. It is integrated with the Visual Studio 2005 Team Suite as a plug-in to provide extra modeling capabilities for performance testing. We illustrate the approach using a case study based on .Net and C#.

  4. Structural domain walls in polar hexagonal manganites

    NASA Astrophysics Data System (ADS)

    Kumagai, Yu

    2014-03-01

    The domain structure in the multiferroic hexagonal manganites is currently intensely investigated, motivated by the observation of intriguing sixfold topological defects at their meeting points [Choi, T. et al,. Nature Mater. 9, 253 (2010).] and nanoscale electrical conductivity at the domain walls [Wu, W. et al., Phys. Rev. Lett. 108, 077203 (2012).; Meier, D. et al., Nature Mater. 11, 284 (2012).], as well as reports of coupling between ferroelectricity, magnetism and structural antiphase domains [Geng, Y. et al., Nano Lett. 12, 6055 (2012).]. The detailed structure of the domain walls, as well as the origin of such couplings, however, was previously not fully understood. In the present study, we have used first-principles density functional theory to calculate the structure and properties of the low-energy structural domain walls in the hexagonal manganites [Kumagai, Y. and Spaldin, N. A., Nature Commun. 4, 1540 (2013).]. We find that the lowest energy domain walls are atomically sharp, with {210}orientation, explaining the orientation of recently observed stripe domains and suggesting their topological protection [Chae, S. C. et al., Phys. Rev. Lett. 108, 167603 (2012).]. We also explain why ferroelectric domain walls are always simultaneously antiphase walls, propose a mechanism for ferroelectric switching through domain-wall motion, and suggest an atomistic structure for the cores of the sixfold topological defects. This work was supported by ETH Zurich, the European Research Council FP7 Advanced Grants program me (grant number 291151), the JSPS Postdoctoral Fellowships for Research Abroad, and the MEXT Elements Strategy Initiative to Form Core Research Center TIES.

  5. Domain decomposition algorithms and computational fluid dynamics

    NASA Technical Reports Server (NTRS)

    Chan, Tony F.

    1988-01-01

    Some of the new domain decomposition algorithms are applied to two model problems in computational fluid dynamics: the two-dimensional convection-diffusion problem and the incompressible driven cavity flow problem. First, a brief introduction to the various approaches of domain decomposition is given, and a survey of domain decomposition preconditioners for the operator on the interface separating the subdomains is then presented. For the convection-diffusion problem, the effect of the convection term and its discretization on the performance of some of the preconditioners is discussed. For the driven cavity problem, the effectiveness of a class of boundary probe preconditioners is examined.

  6. Skyrmions from Instantons inside Domain Walls

    NASA Astrophysics Data System (ADS)

    Eto, Minoru; Nitta, Muneto; Ohashi, Keisuke; Tong, David

    2005-12-01

    Some years ago, Atiyah and Manton described a method to construct approximate Skyrmion solutions from Yang-Mills instantons. Here we present a dynamical realization of this construction using domain walls in a five-dimensional gauge theory. The non-Abelian gauge symmetry is broken in each vacuum but restored in the core of the domain wall, allowing instantons to nestle inside the wall. We show that the world volume dynamics of the wall is given by the Skyrme model, including the four-derivative term, and the instantons appear as domain wall Skyrmions.

  7. Domain-decomposed preconditionings for transport operators

    NASA Technical Reports Server (NTRS)

    Chan, Tony F.; Gropp, William D.; Keyes, David E.

    1991-01-01

    The performance was tested of five different interface preconditionings for domain decomposed convection diffusion problems, including a novel one known as the spectral probe, while varying mesh parameters, Reynolds number, ratio of subdomain diffusion coefficients, and domain aspect ratio. The preconditioners are representative of the range of practically computable possibilities that have appeared in the domain decomposition literature for the treatment of nonoverlapping subdomains. It is shown that through a large number of numerical examples that no single preconditioner can be considered uniformly superior or uniformly inferior to the rest, but that knowledge of particulars, including the shape and strength of the convection, is important in selecting among them in a given problem.

  8. Asymmetric counter propagation of domain walls

    NASA Astrophysics Data System (ADS)

    Andrade-Silva, I.; Clerc, M. G.; Odent, V.

    2016-07-01

    Far from equilibrium systems show different states and domain walls between them. These walls, depending on the type of connected equilibria, exhibit a rich spatiotemporal dynamics. Here, we investigate the asymmetrical counter propagation of domain walls in an in-plane-switching cell filled with a nematic liquid crystal. Experimentally, we characterize the shape and speed of the domain walls. Based on the molecular orientation, we infer that the counter propagative walls have different elastic deformations. These deformations are responsible of the asymmetric counter propagating fronts. Theoretically, based on symmetry arguments, we propose a simple bistable model under the influence of a nonlinear gradient, which qualitatively describes the observed dynamics.

  9. Shape design sensitivity analysis using domain information

    NASA Technical Reports Server (NTRS)

    Seong, Hwal-Gyeong; Choi, Kyung K.

    1985-01-01

    A numerical method for obtaining accurate shape design sensitivity information for built-up structures is developed and demonstrated through analysis of examples. The basic character of the finite element method, which gives more accurate domain information than boundary information, is utilized for shape design sensitivity improvement. A domain approach for shape design sensitivity analysis of built-up structures is derived using the material derivative idea of structural mechanics and the adjoint variable method of design sensitivity analysis. Velocity elements and B-spline curves are introduced to alleviate difficulties in generating domain velocity fields. The regularity requirements of the design velocity field are studied.

  10. Separating Cognitive and Content Domains in Mathematical Competence

    ERIC Educational Resources Information Center

    Harks, Birgit; Klieme, Eckhard; Hartig, Johannes; Leiss, Dominik

    2014-01-01

    The present study investigates the empirical separability of mathematical (a) content domains, (b) cognitive domains, and (c) content-specific cognitive domains. There were 122 items representing two content domains (linear equations vs. theorem of Pythagoras) combined with two cognitive domains (modeling competence vs. technical competence)…

  11. Supporting multiple domains in a single reuse repository

    NASA Technical Reports Server (NTRS)

    Eichmann, David A.

    1992-01-01

    Domain analysis typically results in the construction of a domain-specific repository. Such a repository imposes artificial boundaries on the sharing of similar assets between related domains. A lattice-based approach to repository modeling can preserve a reuser's domain specific view of the repository, while avoiding replication of commonly used assets and supporting a more general perspective on domain interrelationships.

  12. Epistemic Analysis of Interrogative Domains using Cuboids

    NASA Astrophysics Data System (ADS)

    Hughes, Cameron; Hughes, Tracey

    We are interested in analyzing the propositional knowledge extracted by an epistemic agent from interrogative domains. The interrogative domains that have our current focus are taken from transcripts of legal trials, congressional hearings, or law enforcement interrogations. These transcripts have be encoded in XML or HTML formats. The agent uses these transcripts as a primary knowledge source. The complexity, size, scope and potentially conflicting nature of transcripts from interrogative domains bring into question the quality of propositional knowledge that can be garnered by the agent. Epistemic Cuboids or Cubes are used as a knowledge analysis technique that helps determine the quality and quantity of the propositional knowledge extracted by an epistemic agent from an interrogative domain. In this paper we explore how 'Epistemic Cubes' can be used to evaluate the nature of the agent's propositional knowledge.

  13. Substructure coupling in the frequency domain

    NASA Technical Reports Server (NTRS)

    1985-01-01

    Frequency domain analysis was found to be a suitable method for determining the transient response of systems subjected to a wide variety of loads. However, since a large number of calculations are performed within the discrete frequency loop, the method loses it computational efficiency if the loads must be represented by a large number of discrete frequencies. It was also discovered that substructure coupling in the frequency domain work particularly well for analyzing structural system with a small number of interface and loaded degrees of freedom. It was discovered that substructure coupling in the frequency domain can lead to an efficient method of obtaining natural frequencies of undamped structures. It was also found that the damped natural frequencies of a system may be determined using frequency domain techniques.

  14. Resistance domain in type II superconductors

    SciTech Connect

    Gurevich, A.V.; Mints, R.G.

    1980-01-05

    We show that traveling domains with a finite resistance can exist in type II superconductors in the presence of a transport current. An experiment in which this effect generates an alternating electric field and current is proposed.

  15. Antiferromagnetic domains in UPdSn

    SciTech Connect

    Nakotte, H.; Brueck, E.; de Boer, F.R. ); Svoboda, P.; Tuan, N.C.; Havela, L.; Sechovsky, V. ); Robinson, R.A. )

    1993-05-15

    The magnetization of a single crystal of the hexagonal antiferromagnet UPdSn has been studied in fields up to 5 T in order to examine the energetics associated with antiferromagnetic domains. The magnetic unit cell is orthorhombic, so there are three possible domain orientations within the parent lattice. The low-temperature magnetization reflects both spin-flop transition and domain-depopulation effects. Although the interpretation of our results is complicated by the coexistence of these two phenomena, we can conclude that the domain occupancies are history dependent below the spin-reorientation transition which lies at 25 K, but history independent between this transition and [ital T][sub [ital N

  16. Between-domain relations of students' academic emotions and their judgments of school domain similarity

    PubMed Central

    Goetz, Thomas; Haag, Ludwig; Lipnevich, Anastasiya A.; Keller, Melanie M.; Frenzel, Anne C.; Collier, Antonie P. M.

    2014-01-01

    With the aim to deepen our understanding of the between-domain relations of academic emotions, a series of three studies was conducted. We theorized that between-domain relations of trait (i.e., habitual) emotions reflected students' judgments of domain similarities, whereas between-domain relations of state (i.e., momentary) emotions did not. This supposition was based on the accessibility model of emotional self-report, according to which individuals' beliefs tend to strongly impact trait, but not state emotions. The aim of Study 1 (interviews; N = 40; 8th and 11th graders) was to gather salient characteristics of academic domains from students' perspective. In Study 2 (N = 1709; 8th and 11th graders) the 13 characteristics identified in Study 1 were assessed along with academic emotions in four different domains (mathematics, physics, German, and English) using a questionnaire-based trait assessment. With respect to the same domains, state emotions were assessed in Study 3 (N = 121; 8th and 11th graders) by employing an experience sampling approach. In line with our initial assumptions, between-domain relations of trait but not state academic emotions reflected between-domain relations of domain characteristics. Implications for research and practice are discussed. PMID:25374547

  17. Noisy neural nets exhibiting memory domains.

    PubMed

    Anninos, P; Kokkinidis, M; Skouras, A

    1984-08-21

    Previous studies with probabilistic neural nets in which the neural connections are set up by means of chemical markers, revealed the existence of multiple memory domains. We generalized these studies by considering the intrinsic noise of the systems, caused by the spontaneous release of synaptic transmitter substance. A simple mathematical model is developed, which yields characteristics of multiple memory domains analogous to those occurring in noiseless nets.

  18. Planning with Continuous Resources in Stochastic Domains

    NASA Technical Reports Server (NTRS)

    Mausam, Mausau; Benazera, Emmanuel; Brafman, Roneu; Hansen, Eric

    2005-01-01

    We consider the problem of optimal planning in stochastic domains with metric resource constraints. Our goal is to generate a policy whose expected sum of rewards is maximized for a given initial state. We consider a general formulation motivated by our application domain--planetary exploration--in which the choice of an action at each step may depend on the current resource levels. We adapt the forward search algorithm AO* to handle our continuous state space efficiently.

  19. Moving Towards Domain Wall Devices in Ferroics

    NASA Astrophysics Data System (ADS)

    Gregg, Marty

    Domain walls in ferroelectric, ferroelastic and multiferroic oxides are distinct functional materials in their own right. They can be conducting, or even superconducting, when surrounding domains are insulating; they can demonstrate magnetism when the surrounding bulk is non-magnetic and they can contain ordered electrical dipoles when the matrix containing them is non-polar. Since domain walls can also be created, destroyed, and controllably moved from place to place, there is an amazing opportunity for us to design new forms of devices in which functionality is actively and dynamically deployed (now you see it; now you don't). This is the essence of the emerging field known as ``domain wall nanoelectronics''. In time, this arena of research could change the way we think of nanoscale functional devices, moving increasingly towards agile circuitry and neuromorphic device architectures. While the control of domain wall injection, movement and annihilation has been developed rather well in the nanomagnetics community (in race-track and domain wall logic research), similar research has not been widely performed in nanoscale ferroelectrics, ferroelastics and multiferroics. This talk will discuss progress that has been made to date and the way in which nanomagnetics research can be used as a source of inspiration. Site-specific domain wall injection and motion control in both proper and improper ferroelectrics using inhomogeneous electric and elastic fields, as well as dielectric patterning in uniaxial ferroelectrics, will be specifically considered. As will be shown, sufficient control has been developed to allow the creation of a diode for domain wall motion in ferroelectrics, for example. The author acknowledges support from the Engineering and Physical Sciences Research Council (EPSRC).

  20. Determination of the critical residues responsible for cardiac myosin binding protein C's interactions.

    PubMed

    Bhuiyan, Md Shenuarin; Gulick, James; Osinska, Hanna; Gupta, Manish; Robbins, Jeffrey

    2012-12-01

    Despite early demonstrations of myosin binding protein C's (MyBP-C) interaction with actin, different investigators have reached different conclusions regarding the relevant and necessary domains mediating this binding. Establishing the detailed structure-function relationships is needed to fully understand cMyBP-C's ability to impact on myofilament contraction as mutations in different domains are causative for familial hypertrophic cardiomyopathy. We defined cMyBP-C's N-terminal structural domains that are necessary or sufficient to mediate interactions with actin and/or the head region of the myosin heavy chain (S2-MyHC). Using a combination of genetics and functional assays, we defined the actin binding site(s) present in cMyBP-C. We confirmed that cMyBP-C's C1 and m domains productively interact with actin, while S2-MyHC interactions are restricted to the m domain. Using residue-specific mutagenesis, we identified the critical actin binding residues and distinguished them from the residues that were critical for S2-MyHC binding. To validate the structural and functional significance of these residues, we silenced the endogenous cMyBP-C in neonatal rat cardiomyocytes (NRC) using cMyBP-C siRNA, and replaced the endogenous cMyBP-C with normal or actin binding-ablated cMyBP-C. Replacement with actin binding-ablated cMyBP-C showed that the mutated protein did not incorporate into the sarcomere normally. Residues responsible for actin and S2-MyHC binding are partially present in overlapping domains but are unique. Expression of an actin binding-deficient cMyBP-C resulted in abnormal cytosolic distribution of the protein, indicating that interaction with actin is essential for the formation and/or maintenance of normal cMyBP-C sarcomeric distribution.

  1. Mechanical Properties of Nanoscopic Lipid Domains.

    PubMed

    Nickels, Jonathan D; Cheng, Xiaolin; Mostofian, Barmak; Stanley, Christopher; Lindner, Benjamin; Heberle, Frederick A; Perticaroli, Stefania; Feygenson, Mikhail; Egami, Takeshi; Standaert, Robert F; Smith, Jeremy C; Myles, Dean A A; Ohl, Michael; Katsaras, John

    2015-12-23

    The lipid raft hypothesis presents insights into how the cell membrane organizes proteins and lipids to accomplish its many vital functions. Yet basic questions remain about the physical mechanisms that lead to the formation, stability, and size of lipid rafts. As a result, much interest has been generated in the study of systems that contain similar lateral heterogeneities, or domains. In the current work we present an experimental approach that is capable of isolating the bending moduli of lipid domains. This is accomplished using neutron scattering and its unique sensitivity to the isotopes of hydrogen. Combining contrast matching approaches with inelastic neutron scattering, we isolate the bending modulus of ∼13 nm diameter domains residing in 60 nm unilamellar vesicles, whose lipid composition mimics the mammalian plasma membrane outer leaflet. Importantly, the bending modulus of the nanoscopic domains differs from the modulus of the continuous phase surrounding them. From additional structural measurements and all-atom simulations, we also determine that nanoscopic domains are in-register across the bilayer leaflets. Taken together, these results inform a number of theoretical models of domain/raft formation and highlight the fact that mismatches in bending modulus must be accounted for when explaining the emergence of lateral heterogeneities in lipid systems and biological membranes.

  2. Tandem BRCT Domains: DNA's Praetorian Guard.

    PubMed

    Mesquita, Rafael D; Woods, Nicholas T; Seabra-Junior, Eloy S; Monteiro, Alvaro N A

    2010-11-01

    The cell's ability to sense and respond to specific stimuli is a complex system derived from precisely regulated protein-protein interactions. Some of these protein-protein interactions are mediated by the recognition of linear peptide motifs by protein modular domains. BRCT (BRCA1 C-terminal) domains and their linear motif counterparts, which contain phosphoserines, are one such pair-wise interaction system that seems to have evolved to serve as a surveillance system to monitor threats to the cell's genetic integrity. Evidence indicates that BRCT domains found in tandem can cooperate to provide sequence-specific binding of phosphorylated peptides as is the case for the breast and ovarian cancer susceptibility gene BRCA1 and the PAX transcription factor-interacting protein PAXIP1. Particular interest has been paid to tandem BRCT domains as "readers" of signaling events in the form of phosphorylated serine moieties induced by the activation of DNA damage response kinases ATM, ATR, and DNA-PK. However, given the diversity of tandem BRCT-containing proteins, questions remain as to the origin and evolution of this domain. Here, we discuss emerging views of the origin and evolving roles of tandem BRCT domain repeats in the DNA damage response.

  3. Functional domains of the poliovirus receptor

    SciTech Connect

    Koike, Satoshi; Ise, Iku; Nomoto, Akio )

    1991-05-15

    A number of mutant cDNAs of the human poliovirus receptor were constructed to identify essential regions of the molecule as the receptor. All mutant cDNAs carrying the sequence coding for the entire N-terminal immunoglobulin-like domain (domain I) confer permissiveness for poliovirus to mouse L cells, but a mutant cDNA lacking the sequence for domain I does not. The transformants permissive for poliovirus were able to bind the virus and were also recognized by monoclonal antibody D171, which competes with poliovirus for the cellular receptor. These results strongly suggest that the poliovirus binding site resides in domain I of the receptor. Mutant cDNAs for the sequence encoding the intracellular peptide were also constructed and expressed in mouse L cells. Susceptibility of these cells to poliovirus revealed that the entire putative cytoplasmic domain is not essential for virus infection. Thus, the cytoplasmic domain of the molecule appears not to play a role in the penetration of poliovirus.

  4. Structured hints : extracting and abstracting domain expertise.

    SciTech Connect

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

    2009-03-16

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

  5. Incubational domain characterization in lightly doped ceria

    SciTech Connect

    Li Zhipeng; Mori, Toshiyuki; John Auchterlonie, Graeme; Zou Jin; Drennan, John

    2012-08-15

    Microstructures of both Gd- and Y-doped ceria with different doping level (i.e., 10 at% and 25 at%) have been comprehensively characterized by means of high resolution transmission electron microscopy and selected area electron diffraction. Coherent nano-sized domains can be widely observed in heavily doped ceria. Nevertheless, it was found that a large amount of dislocations actually exist in lightly doped ceria instead of heavily doped ones. Furthermore, incubational domains can be detected in lightly doped ceria, with dislocations located at the interfaces. The interactions between such linear dislocations and dopant defects have been simulated accordingly. As a consequence, the formation mechanism of incubational domains is rationalized in terms of the interaction between intrinsic dislocations of doped ceria and dopant defects. This study offers the insights into the initial state and related mechanism of the formation of nano-sized domains, which have been widely observed in heavily rare-earth-doped ceria in recent years. - Graphical abstract: Interactions between dislocations and dopants lead to incubational domain formation in lightly doped ceria. Highlights: Black-Right-Pointing-Pointer Microstructures were characterized in both heavily and light Gd-/Y-doped ceria. Black-Right-Pointing-Pointer Dislocations are existed in lightly doped ceria rather than heavily doped one. Black-Right-Pointing-Pointer Interactions between dislocations and dopant defects were simulated. Black-Right-Pointing-Pointer Formation of dislocation associated incubational domain is rationalized.

  6. An optical space domain volume holographic correlator

    NASA Astrophysics Data System (ADS)

    Birch, Philip; Gardezi, Akber; Mitra, Bhargav; Young, Rupert; Chatwin, Chris

    2009-04-01

    We propose a novel space domain volume holographic correlator system. One of the limitations of conventional correlators is the bandwidth limits imposed by updating the filter and the readout speed of the CCD. The volume holographic correlator overcomes these by storing a large number of filters that can be interrogated simultaneously. By using angle multiplexing, the match can be read out onto a high speed linear array of sensors. A scanning window can be used to implement shift invariance, thus, making the system operate like a space domain correlator. The space domain correlation method offers an advantage over the frequency domain correlator in that the correlation filter no longer has shift invariance imposed on it since the kernel can be modified depending on its position. This maybe used for normalising the kernel or imposing some non-linearity in an attempt to improve performance. However, one of the key advantages of the frequency domain method is lost using this technique, namely the speed of the computation. A large kernel space-domain correlation, performed on a computer, will be very slow compared to what is achievable using a 4f optical correlator. We propose a method of implementing this using the scanning holographic memory based correlator.

  7. Domain wall geometry controls conduction in ferroelectrics.

    PubMed

    Vasudevan, R K; Morozovska, A N; Eliseev, E A; Britson, J; Yang, J-C; Chu, Y-H; Maksymovych, P; Chen, L Q; Nagarajan, V; Kalinin, S V

    2012-11-14

    A new paradigm of domain wall nanoelectronics has emerged recently, in which the domain wall in a ferroic is itself an active device element. The ability to spatially modulate the ferroic order parameter within a single domain wall allows the physical properties to be tailored at will and hence opens vastly unexplored device possibilities. Here, we demonstrate via ambient and ultrahigh-vacuum (UHV) scanning probe microscopy (SPM) measurements in bismuth ferrite that the conductivity of the domain walls can be modulated by up to 500% in the spatial dimension as a function of domain wall curvature. Landau-Ginzburg-Devonshire calculations reveal the conduction is a result of carriers or vacancies migrating to neutralize the charge at the formed interface. Phase-field modeling indicates that anisotropic potential distributions can occur even for initially uncharged walls, from polarization dynamics mediated by elastic effects. These results are the first proof of concept for modulation of charge as a function of domain wall geometry by a proximal probe, thereby expanding potential applications for oxide ferroics in future nanoscale electronics. PMID:22994244

  8. Human-computer interface incorporating personal and application domains

    DOEpatents

    Anderson, Thomas G.

    2011-03-29

    The present invention provides a human-computer interface. The interface includes provision of an application domain, for example corresponding to a three-dimensional application. The user is allowed to navigate and interact with the application domain. The interface also includes a personal domain, offering the user controls and interaction distinct from the application domain. The separation into two domains allows the most suitable interface methods in each: for example, three-dimensional navigation in the application domain, and two- or three-dimensional controls in the personal domain. Transitions between the application domain and the personal domain are under control of the user, and the transition method is substantially independent of the navigation in the application domain. For example, the user can fly through a three-dimensional application domain, and always move to the personal domain by moving a cursor near one extreme of the display.

  9. Human-computer interface incorporating personal and application domains

    DOEpatents

    Anderson, Thomas G.

    2004-04-20

    The present invention provides a human-computer interface. The interface includes provision of an application domain, for example corresponding to a three-dimensional application. The user is allowed to navigate and interact with the application domain. The interface also includes a personal domain, offering the user controls and interaction distinct from the application domain. The separation into two domains allows the most suitable interface methods in each: for example, three-dimensional navigation in the application domain, and two- or three-dimensional controls in the personal domain. Transitions between the application domain and the personal domain are under control of the user, and the transition method is substantially independent of the navigation in the application domain. For example, the user can fly through a three-dimensional application domain, and always move to the personal domain by moving a cursor near one extreme of the display.

  10. A simple method for converting frequency domain aerodynamics to the time domain

    NASA Technical Reports Server (NTRS)

    Dowell, E. H.

    1980-01-01

    A simple, direct procedure was developed for converting frequency domain aerodynamics into indicial aerodynamics. The data required for aerodynamic forces in the frequency domain may be obtained from any available (linear) theory. The method retains flexibility for the analyst and is based upon the particular character of the frequency domain results. An evaluation of the method was made for incompressible, subsonic, and transonic two dimensional flows.

  11. Low energy electron imaging of domains and domain walls in magnesium-doped lithium niobate

    NASA Astrophysics Data System (ADS)

    Nataf, G. F.; Grysan, P.; Guennou, M.; Kreisel, J.; Martinotti, D.; Rountree, C. L.; Mathieu, C.; Barrett, N.

    2016-09-01

    The understanding of domain structures, specifically domain walls, currently attracts a significant attention in the field of (multi)-ferroic materials. In this article, we analyze contrast formation in full field electron microscopy applied to domains and domain walls in the uniaxial ferroelectric lithium niobate, which presents a large 3.8 eV band gap and for which conductive domain walls have been reported. We show that the transition from Mirror Electron Microscopy (MEM – electrons reflected) to Low Energy Electron Microscopy (LEEM – electrons backscattered) gives rise to a robust contrast between domains with upwards (Pup) and downwards (Pdown) polarization, and provides a measure of the difference in surface potential between the domains. We demonstrate that out-of-focus conditions of imaging produce contrast inversion, due to image distortion induced by charged surfaces, and also carry information on the polarization direction in the domains. Finally, we show that the intensity profile at domain walls provides experimental evidence for a local stray, lateral electric field.

  12. Putative Domain-Domain Interactions in the Vesicular Stomatitis Virus L Polymerase Protein Appendage Region

    PubMed Central

    Ruedas, John B.

    2014-01-01

    ABSTRACT The multidomain polymerase protein (L) of nonsegmented negative-strand (NNS) RNA viruses catalyzes transcription and replication of the virus genome. The N-terminal half of the protein forms a ring-like polymerase structure, while the C-terminal half encoding viral mRNA transcript modifications consists of a flexible appendage with three distinct globular domains. To gain insight into putative transient interactions between L domains during viral RNA synthesis, we exchanged each of the four distinct regions encompassing the appendage region of vesicular stomatitis virus (VSV) Indiana serotype L protein with their counterparts from VSV New Jersey and analyzed effects on virus polymerase activity in a minigenome system. The methyltransferase domain exchange yielded a fully active polymerase protein, which functioned as well as wild-type L in the context of a recombinant virus. Exchange of the downstream C-terminal nonconserved region abolished activity, but coexchanging it with the methyltransferase domain generated a polymerase favoring replicase over transcriptase activity, providing strong evidence of interaction between these two regions. Exchange of the capping enzyme domain or the adjacent nonconserved region thought to function as an “unstructured” linker also abrogated polymerase activity even when either domain was coexchanged with other appendage domains. Further probing of the putative linker segment using in-frame enhanced green fluorescent protein (EGFP) insertions similarly abrogated activity. We discuss the implications of these findings with regard to L protein appendage domain structure and putative domain-domain interactions required for polymerase function. IMPORTANCE NNS viruses include many well-known human pathogens (e.g., rabies, measles, and Ebola viruses), as well as emerging viral threats (e.g., Nipah and Hendra viruses). These viruses all encode a large L polymerase protein similarly organized into multiple domains that work in

  13. Low energy electron imaging of domains and domain walls in magnesium-doped lithium niobate

    NASA Astrophysics Data System (ADS)

    Nataf, G. F.; Grysan, P.; Guennou, M.; Kreisel, J.; Martinotti, D.; Rountree, C. L.; Mathieu, C.; Barrett, N.

    2016-09-01

    The understanding of domain structures, specifically domain walls, currently attracts a significant attention in the field of (multi)-ferroic materials. In this article, we analyze contrast formation in full field electron microscopy applied to domains and domain walls in the uniaxial ferroelectric lithium niobate, which presents a large 3.8 eV band gap and for which conductive domain walls have been reported. We show that the transition from Mirror Electron Microscopy (MEM - electrons reflected) to Low Energy Electron Microscopy (LEEM - electrons backscattered) gives rise to a robust contrast between domains with upwards (Pup) and downwards (Pdown) polarization, and provides a measure of the difference in surface potential between the domains. We demonstrate that out-of-focus conditions of imaging produce contrast inversion, due to image distortion induced by charged surfaces, and also carry information on the polarization direction in the domains. Finally, we show that the intensity profile at domain walls provides experimental evidence for a local stray, lateral electric field.

  14. Low energy electron imaging of domains and domain walls in magnesium-doped lithium niobate

    PubMed Central

    Nataf, G. F.; Grysan, P.; Guennou, M.; Kreisel, J.; Martinotti, D.; Rountree, C. L.; Mathieu, C.; Barrett, N.

    2016-01-01

    The understanding of domain structures, specifically domain walls, currently attracts a significant attention in the field of (multi)-ferroic materials. In this article, we analyze contrast formation in full field electron microscopy applied to domains and domain walls in the uniaxial ferroelectric lithium niobate, which presents a large 3.8 eV band gap and for which conductive domain walls have been reported. We show that the transition from Mirror Electron Microscopy (MEM – electrons reflected) to Low Energy Electron Microscopy (LEEM – electrons backscattered) gives rise to a robust contrast between domains with upwards (Pup) and downwards (Pdown) polarization, and provides a measure of the difference in surface potential between the domains. We demonstrate that out-of-focus conditions of imaging produce contrast inversion, due to image distortion induced by charged surfaces, and also carry information on the polarization direction in the domains. Finally, we show that the intensity profile at domain walls provides experimental evidence for a local stray, lateral electric field. PMID:27608605

  15. A new and unexpected domain-domain interaction in the AraC protein.

    PubMed

    Cole, Stephanie Dirla; Schleif, Robert

    2012-05-01

    An interaction between the dimerization domains and DNA binding domains of the dimeric AraC protein has previously been shown to facilitate repression of the Escherichia coli araBAD operon by AraC in the absence of arabinose. A new interaction between the domains of AraC in the presence of arabinose is reported here, the regulatory consequences of which are unknown. Evidence for the interaction is the following: the dissociation rate of arabinose-bound AraC from half-site DNA is considerably faster than that of free DNA binding domain, and the affinity of the dimerization domains for arabinose is increased when half-site DNA is bound. In addition, an increase in the fluorescence intensity of tryptophan residues located in the arabinose-bound dimerization domain is observed upon binding of half-site DNA to the DNA binding domains. Direct physical evidence of the new domain-domain interaction is demonstrated by chemical crosslinking and NMR experiments. PMID:22383259

  16. Low energy electron imaging of domains and domain walls in magnesium-doped lithium niobate.

    PubMed

    Nataf, G F; Grysan, P; Guennou, M; Kreisel, J; Martinotti, D; Rountree, C L; Mathieu, C; Barrett, N

    2016-01-01

    The understanding of domain structures, specifically domain walls, currently attracts a significant attention in the field of (multi)-ferroic materials. In this article, we analyze contrast formation in full field electron microscopy applied to domains and domain walls in the uniaxial ferroelectric lithium niobate, which presents a large 3.8 eV band gap and for which conductive domain walls have been reported. We show that the transition from Mirror Electron Microscopy (MEM - electrons reflected) to Low Energy Electron Microscopy (LEEM - electrons backscattered) gives rise to a robust contrast between domains with upwards (Pup) and downwards (Pdown) polarization, and provides a measure of the difference in surface potential between the domains. We demonstrate that out-of-focus conditions of imaging produce contrast inversion, due to image distortion induced by charged surfaces, and also carry information on the polarization direction in the domains. Finally, we show that the intensity profile at domain walls provides experimental evidence for a local stray, lateral electric field. PMID:27608605

  17. Algorithms for propagating uncertainty across heterogeneous domains

    SciTech Connect

    Cho, Heyrim; Yang, Xiu; Venturi, D.; Karniadakis, George E.

    2015-12-30

    We address an important research area in stochastic multi-scale modeling, namely the propagation of uncertainty across heterogeneous domains characterized by partially correlated processes with vastly different correlation lengths. This class of problems arise very often when computing stochastic PDEs and particle models with stochastic/stochastic domain interaction but also with stochastic/deterministic coupling. The domains may be fully embedded, adjacent or partially overlapping. The fundamental open question we address is the construction of proper transmission boundary conditions that preserve global statistical properties of the solution across different subdomains. Often, the codes that model different parts of the domains are black-box and hence a domain decomposition technique is required. No rigorous theory or even effective empirical algorithms have yet been developed for this purpose, although interfaces defined in terms of functionals of random fields (e.g., multi-point cumulants) can overcome the computationally prohibitive problem of preserving sample-path continuity across domains. The key idea of the different methods we propose relies on combining local reduced-order representations of random fields with multi-level domain decomposition. Specifically, we propose two new algorithms: The first one enforces the continuity of the conditional mean and variance of the solution across adjacent subdomains by using Schwarz iterations. The second algorithm is based on PDE-constrained multi-objective optimization, and it allows us to set more general interface conditions. The effectiveness of these new algorithms is demonstrated in numerical examples involving elliptic problems with random diffusion coefficients, stochastically advected scalar fields, and nonlinear advection-reaction problems with random reaction rates.

  18. Dual-domain point diffraction interferometer

    DOEpatents

    Naulleau, Patrick P.; Goldberg, Kenneth Alan

    2000-01-01

    A hybrid spatial/temporal-domain point diffraction interferometer (referred to as the dual-domain PS/PDI) that is capable of suppressing the scattered-reference-light noise that hinders the conventional PS/PDI is provided. The dual-domain PS/PDI combines the separate noise-suppression capabilities of the widely-used phase-shifting and Fourier-transform fringe pattern analysis methods. The dual-domain PS/PDI relies on both a more restrictive implementation of the image plane PS/PDI mask and a new analysis method to be applied to the interferograms generated and recorded by the modified PS/PDI. The more restrictive PS/PDI mask guarantees the elimination of spatial-frequency crosstalk between the signal and the scattered-light noise arising from scattered-reference-light interfering with the test beam. The new dual-domain analysis method is then used to eliminate scattered-light noise arising from both the scattered-reference-light interfering with the test beam and the scattered-reference-light interfering with the "true" pinhole-diffracted reference light. The dual-domain analysis method has also been demonstrated to provide performance enhancement when using the non-optimized standard PS/PDI design. The dual-domain PS/PDI is essentially a three-tiered filtering system composed of lowpass spatial-filtering the test-beam electric field using the more restrictive PS/PDI mask, bandpass spatial-filtering the individual interferogram irradiance frames making up the phase-shifting series, and bandpass temporal-filtering the phase-shifting series as a whole.

  19. Polar domain walls trigger magnetoelectric coupling

    PubMed Central

    Fontcuberta, Josep; Skumryev, Vassil; Laukhin, Vladimir; Granados, Xavier; Salje, Ekhard K. H.

    2015-01-01

    Interface physics in oxides heterostructures is pivotal in material’s science. Domain walls (DWs) in ferroic systems are examples of naturally occurring interfaces, where order parameter of neighboring domains is modified and emerging properties may develop. Here we show that electric tuning of ferroelastic domain walls in SrTiO3 leads to dramatic changes of the magnetic domain structure of a neighboring magnetic layer (La1/2Sr1/2MnO3) epitaxially clamped on a SrTiO3 substrate. We show that the properties of the magnetic layer are intimately connected to the existence of polar regions at twin boundaries of SrTiO3, developing at , that can be electrically modulated. These findings illustrate that by exploiting the responsiveness of DWs nanoregions to external stimuli, even in absence of any domain contribution, prominent and adjustable macroscopic reactions of neighboring layers can be obtained. We conclude that polar DWs, known to exist in other materials, can be used to trigger tunable responses and may lead to new ways for the manipulation of interfacial emerging properties. PMID:26387597

  20. The architecture of the protein domain universe.

    PubMed

    Dokholyan, Nikolay V

    2005-03-14

    Understanding the design of the universe of protein structures may provide insights into protein evolution. We study the architecture of the protein domain universe, which has been found to poses peculiar scale-free properties. We examine the origin of these scale-free properties of the graph of protein domain structures (PDUG) and determine that that the PDUG is not modular, i.e. it does not consist of modules with uniform properties. Instead, we find the PDUG to be self-similar at all scales. We further characterize the PDUG architecture by studying the properties of the hub nodes that are responsible for the scale-free connectivity of the PDUG. We introduce a measure of the betweenness centrality of protein domains in the PDUG and find a power-law distribution of the betweenness centrality values. The scale-free distribution of hubs in the protein universe suggests that a set of specific statistical mechanics models, such as the self-organized criticality model, can potentially identify the principal driving forces of protein evolution. We also find a gatekeeper protein domain, removal of which partitions the largest cluster into two large sub-clusters. We suggest that the loss of such gatekeeper protein domains in the course of evolution is responsible for the creation of new fold families.

  1. Generalized vector calculus on convex domain

    NASA Astrophysics Data System (ADS)

    Agrawal, Om P.; Xu, Yufeng

    2015-06-01

    In this paper, we apply recently proposed generalized integral and differential operators to develop generalized vector calculus and generalized variational calculus for problems defined over a convex domain. In particular, we present some generalization of Green's and Gauss divergence theorems involving some new operators, and apply these theorems to generalized variational calculus. For fractional power kernels, the formulation leads to fractional vector calculus and fractional variational calculus for problems defined over a convex domain. In special cases, when certain parameters take integer values, we obtain formulations for integer order problems. Two examples are presented to demonstrate applications of the generalized variational calculus which utilize the generalized vector calculus developed in the paper. The first example leads to a generalized partial differential equation and the second example leads to a generalized eigenvalue problem, both in two dimensional convex domains. We solve the generalized partial differential equation by using polynomial approximation. A special case of the second example is a generalized isoperimetric problem. We find an approximate solution to this problem. Many physical problems containing integer order integrals and derivatives are defined over arbitrary domains. We speculate that future problems containing fractional and generalized integrals and derivatives in fractional mechanics will be defined over arbitrary domains, and therefore, a general variational calculus incorporating a general vector calculus will be needed for these problems. This research is our first attempt in that direction.

  2. Domain Wall structures in wide permalloy strips

    NASA Astrophysics Data System (ADS)

    Estevez, Virginia; Laurson, Lasse

    2015-03-01

    We analyze numerically the equilibrium micromagnetic domain wall structures encountered in Permalloy strips of a wide range of thicknesses and widths, with strip widths up to several micrometers. By performing an extensive set of micromagnetic simulations, we show that the equilibrium phase diagram of the domain wall structures exhibits in addition to the previously found structures (symmetric and asymmetric transverse wall and vortex wall) also a double-vortex domain wall for large enough strip widths and thicknesses. In general, shape anisotropy is less important for wider strips, and thus energy minima with more complex spin structures closing the flux more efficiently than those found before for narrow strips may appear. Also several metastable domain wall structures are found, such as structures with three or four vortices or two vortices and an antivortex. We discuss the details of the relaxation process, including the effect of varying the magnitude of the Gilbert damping constant, and the role of using different initial conditions. Finally, we also consider the field-driven dynamics of the double-vortex domain wall.

  3. Domain walls as probes of gravity

    SciTech Connect

    Dvali, Gia; Gabadadze, Gregory; Pujolas, Oriol; Rahman, Rakibur

    2007-06-15

    We show that domain walls are probes that enable one to distinguish large-distance modified gravity from general relativity (GR) at short distances. For example, low-tension domain walls are stealth in modified gravity, while they do produce global gravitational effects in GR. We demonstrate this by finding exact solutions for various domain walls in the DGP model. A wall with tension lower than the fundamental Planck scale does not inflate and has no gravitational effects on a 4D observer, since its 4D tension is completely screened by gravity itself. We argue that this feature remains valid in a generic class of models of infrared modified gravity. As a byproduct, we obtain exact solutions for supermassive codimension-2 branes.

  4. Hallucinating face in the DCT domain.

    PubMed

    Zhang, Wei; Cham, Wai-Kuen

    2011-10-01

    In this paper, we propose a novel learning-based face hallucination framework built in the DCT domain, which can produce a high-resolution face image from a single low-resolution one. The problem is formulated as inferring the DCT coefficients in frequency domain instead of estimating pixel intensities in spatial domain. Our study shows that DC coefficients can be estimated fairly accurately by simple interpolation-based methods. AC coefficients, which contain the information of local features of face image, cannot be estimated well using interpolation. A simple but effective learning-based inference model is proposed to infer the ac coefficients. Experiments have been conducted to demonstrate the effectiveness of the proposed method in producing high quality hallucinated face images.

  5. Formal Problem Domain Modeling within MDA

    NASA Astrophysics Data System (ADS)

    Osis, Janis; Asnina, Erika; Grave, Andrejs

    The proposed approach called Topological Functioning Modeling for Model Driven Architecture (TFM4MDA) uses formal mathematical foundations of Topological Functioning Model (TFM). It introduces the main feature of MDA - Separation of Concerns by formal analysis of a business system, enables mapping to functional requirements and verifying whether those requirements are in conformity with the TFM of the problem domain. By using a goal-based method, a holistic behavior of the planned application can be decomposed in accordance with the goals. Graph transformation from the TFM to a conceptual model (or a domain object model) enables establishing the definition of domain concepts and their relations. The paper also suggests a concept of a tool for TFM4MDA, which is realized as an Eclipse plug-in.

  6. On thick domain walls in general relativity

    NASA Technical Reports Server (NTRS)

    Goetz, Guenter; Noetzold, Dirk

    1989-01-01

    Planar scalar field configurations in general relativity differ considerably from those in flat space. It is shown that static domain walls of finite thickness in curved space-time do not possess a reflection symmetry. At infinity, the space-time tends to the Taub vacuum on one side of the wall and to the Minkowski vacuum (Rindler space-time) on the other. Massive test particles are always accelerated towards the Minkowski side, i.e., domain walls are attractive on the Taub side, but repulsive on the Minkowski side (Taub-vacuum cleaner). It is also proved that the pressure in all directions is always negative. Finally, a brief comment is made concerning the possibility of infinite, i.e., bigger than horizon size, domain walls in our universe. All of the results are independent of the form of the potential V(phi) greater than or equal to 0 of the scalar field phi.

  7. Domain Size Distribution in Segregating Binary Superfluids

    NASA Astrophysics Data System (ADS)

    Takeuchi, Hiromitsu

    2016-05-01

    Domain size distribution in phase separating binary Bose-Einstein condensates is studied theoretically by numerically solving the Gross-Pitaevskii equations at zero temperature. We show that the size distribution in the domain patterns arising from the dynamic instability obeys a power law in a scaling regime according to the dynamic scaling analysis based on the percolation theory. The scaling behavior is kept during the relaxation dynamics until the characteristic domain size becomes comparable to the linear size of the system, consistent with the dynamic scaling hypothesis of the phase-ordering kinetics. Our numerical experiments indicate the existence of a different scaling regime in the size distribution function, which can be caused by the so-called coreless vortices.

  8. Anomalous feedback and negative domain wall resistance

    NASA Astrophysics Data System (ADS)

    Cheng, Ran; Zhu, Jian-Gang; Xiao, Di

    2016-11-01

    Magnetic induction can be regarded as a negative feedback effect, where the motive-force opposes the change of magnetic flux that generates the motive-force. In artificial electromagnetics emerging from spintronics, however, this is not necessarily the case. By studying the current-induced domain wall dynamics in a cylindrical nanowire, we show that the spin motive-force exerting on electrons can either oppose or support the applied current that drives the domain wall. The switching into the anomalous feedback regime occurs when the strength of the dissipative torque β is about twice the value of the Gilbert damping constant α. The anomalous feedback manifests as a negative domain wall resistance, which has an analogy with the water turbine.

  9. Frequency-domain analysis of absolute gravimeters

    NASA Astrophysics Data System (ADS)

    Svitlov, S.

    2012-12-01

    An absolute gravimeter is analysed as a linear time-invariant system in the frequency domain. Frequency responses of absolute gravimeters are derived analytically based on the propagation of the complex exponential signal through their linear measurement functions. Depending on the model of motion and the number of time-distance coordinates, an absolute gravimeter is considered as a second-order (three-level scheme) or third-order (multiple-level scheme) low-pass filter. It is shown that the behaviour of an atom absolute gravimeter in the frequency domain corresponds to that of the three-level corner-cube absolute gravimeter. Theoretical results are applied for evaluation of random and systematic measurement errors and optimization of an experiment. The developed theory agrees with known results of an absolute gravimeter analysis in the time and frequency domains and can be used for measurement uncertainty analyses, building of vibration-isolation systems and synthesis of digital filtering algorithms.

  10. On automating domain connectivity for overset grids

    NASA Technical Reports Server (NTRS)

    Chiu, Ing-Tsau; Meakin, Robert L.

    1995-01-01

    An alternative method for domain connectivity among systems of overset grids is presented. Reference uniform Cartesian systems of points are used to achieve highly efficient domain connectivity, and form the basis for a future fully automated system. The Cartesian systems are used to approximate body surfaces and to map the computational space of component grids. By exploiting the characteristics of Cartesian systems, Chimera type hole-cutting and identification of donor elements for intergrid boundary points can be carried out very efficiently. The method is tested for a range of geometrically complex multiple-body overset grid systems. A dynamic hole expansion/contraction algorithm is also implemented to obtain optimum domain connectivity; however, it is tested only for geometry of generic shapes.

  11. Domain switching of fatigued ferroelectric thin films

    SciTech Connect

    Tak Lim, Yun; Yeog Son, Jong E-mail: hoponpop@ulsan.ac.kr; Shin, Young-Han E-mail: hoponpop@ulsan.ac.kr

    2014-05-12

    We investigate the domain wall speed of a ferroelectric PbZr{sub 0.48}Ti{sub 0.52}O{sub 3} (PZT) thin film using an atomic force microscope incorporated with a mercury-probe system to control the degree of electrical fatigue. The depolarization field in the PZT thin film decreases with increasing the degree of electrical fatigue. We find that the wide-range activation field previously reported in ferroelectric domains result from the change of the depolarization field caused by the electrical fatigue. Domain wall speed exhibits universal behavior to the effective electric field (defined by an applied electric field minus the depolarization field), regardless of the degree of the electrical fatigue.

  12. Chromatin Domains: The Unit of Chromosome Organization.

    PubMed

    Dixon, Jesse R; Gorkin, David U; Ren, Bing

    2016-06-01

    How eukaryotic chromosomes fold inside the nucleus is an age-old question that remains unanswered today. Early biochemical and microscopic studies revealed the existence of chromatin domains and loops as a pervasive feature of interphase chromosomes, but the biological implications of such organizational features were obscure. Genome-wide analysis of pair-wise chromatin interactions using chromatin conformation capture (3C)-based techniques has shed new light on the organization of chromosomes in interphase nuclei. Particularly, the finding of cell-type invariant, evolutionarily conserved topologically associating domains (TADs) in a broad spectrum of cell types has provided a new molecular framework for the study of animal development and human diseases. Here, we review recent progress in characterization of such chromatin domains and delineation of mechanisms of their formation in animal cells. PMID:27259200

  13. Targeting SH2 domains in breast cancer

    PubMed Central

    Morlacchi, Pietro; Robertson, Fredika M; Klostergaard, Jim; McMurray, John S

    2014-01-01

    Breast cancer is among the most commonly diagnosed cancer types in women worldwide and is the second leading cause of cancer-related disease in the USA. SH2 domains recruit signaling proteins to phosphotyrosine residues on aberrantly activated growth factor and cytokine receptors and contribute to cancer cell cycling, metastasis, angiogenesis and so on. Herein we review phosphopeptide mimetic and small-molecule approaches targeting the SH2 domains of Grb2, Grb7 and STAT3 that inhibit their targets and reduce proliferation in in vitro breast cancer models. Only STAT3 inhibitors have been evaluated in in vivo models and have led to tumor reduction. Taken together, these studies suggest that targeting SH2 domains is an important approach to the treatment of breast cancer. PMID:25495984

  14. Time domain reflectometry in time variant plasmas

    NASA Technical Reports Server (NTRS)

    Scherner, Michael J.

    1992-01-01

    The effects of time-dependent electron density fluctuations on a synthesized time domain reflectometry response of a one-dimensional cold plasma sheath are considered. Numerical solutions of the Helmholtz wave equation, which describes the electric field of a normally incident plane wave in a specified static electron density profile, are used. A study of the effects of Doppler shifts resulting from moving density fluctuations in the electron density profile of the sheath is included. Varying electron density levels corrupt time domain and distance measurements. Reducing or modulating the electron density levels of a given electron density profile affects the time domain response of a plasma and results in motion of the turning point, and the effective motion has a significant effect on measuring electron density locations.

  15. A Domain Description Language for Data Processing

    NASA Technical Reports Server (NTRS)

    Golden, Keith

    2003-01-01

    We discuss an application of planning to data processing, a planning problem which poses unique challenges for domain description languages. We discuss these challenges and why the current PDDL standard does not meet them. We discuss DPADL (Data Processing Action Description Language), a language for describing planning domains that involve data processing. DPADL is a declarative, object-oriented language that supports constraints and embedded Java code, object creation and copying, explicit inputs and outputs for actions, and metadata descriptions of existing and desired data. DPADL is supported by the IMAGEbot system, which we are using to provide automation for an ecological forecasting application. We compare DPADL to PDDL and discuss changes that could be made to PDDL to make it more suitable for representing planning domains that involve data processing actions.

  16. Multilevel domain decomposition for electronic structure calculations

    SciTech Connect

    Barrault, M. . E-mail: maxime.barrault@edf.fr; Cances, E. . E-mail: cances@cermics.enpc.fr; Hager, W.W. . E-mail: hager@math.ufl.edu; Le Bris, C. . E-mail: lebris@cermics.enpc.fr

    2007-03-01

    We introduce a new multilevel domain decomposition method (MDD) for electronic structure calculations within semi-empirical and density functional theory (DFT) frameworks. This method iterates between local fine solvers and global coarse solvers, in the spirit of domain decomposition methods. Using this approach, calculations have been successfully performed on several linear polymer chains containing up to 40,000 atoms and 200,000 atomic orbitals. Both the computational cost and the memory requirement scale linearly with the number of atoms. Additional speed-up can easily be obtained by parallelization. We show that this domain decomposition method outperforms the density matrix minimization (DMM) method for poor initial guesses. Our method provides an efficient preconditioner for DMM and other linear scaling methods, variational in nature, such as the orbital minimization (OM) procedure.

  17. Comparing and Contrasting Consensus versus Empirical Domains

    PubMed Central

    Jason, Leonard A.; Kot, Bobby; Sunnquist, Madison; Brown, Abigail; Reed, Jordan; Furst, Jacob; Newton, Julia L.; Strand, Elin Bolle; Vernon, Suzanne D.

    2015-01-01

    Background Since the publication of the CFS case definition [1], there have been a number of other criteria proposed including the Canadian Consensus Criteria [2] and the Myalgic Encephalomyelitis: International Consensus Criteria. [3] Purpose The current study compared these domains that were developed through consensus methods to one obtained through more empirical approaches using factor analysis. Methods Using data mining, we compared and contrasted fundamental features of consensus-based criteria versus empirical latent factors. In general, these approaches found the domain of Fatigue/Post-exertional malaise as best differentiating patients from controls. Results Findings indicated that the Fukuda et al. criteria had the worst sensitivity and specificity. Conclusions These outcomes might help both theorists and researchers better determine which fundamental domains to be used for the case definition. PMID:26977374

  18. Electric-field-driven dynamics of magnetic domain walls in magnetic nanowires patterned on ferroelectric domains

    NASA Astrophysics Data System (ADS)

    Van de Wiele, Ben; Leliaert, Jonathan; Franke, Kévin J. A.; van Dijken, Sebastiaan

    2016-03-01

    Strong coupling of magnetic domain walls onto straight ferroelastic boundaries of a ferroelectric layer enables full and reversible electric-field control of magnetic domain wall motion. In this paper, the dynamics of this new driving mechanism is analyzed using micromagnetic simulations. We show that transverse domain walls with a near-180° spin structure are stabilized in magnetic nanowires and that electric fields can move these walls with high velocities. Above a critical velocity, which depends on material parameters, nanowire geometry and the direction of domain wall motion, the magnetic domain walls depin abruptly from the ferroelastic boundaries. Depinning evolves either smoothly or via the emission and annihilation of a vortex or antivortex core (Walker breakdown). In both cases, the magnetic domain wall slows down after depinning in an oscillatory fashion and eventually comes to a halt. The simulations provide design rules for hybrid ferromagnetic-ferroelectric domain-wall-based devices and indicate that material disorder and structural imperfections only influence Walker-breakdown-like depinning at high domain wall velocities.

  19. Domain decomposition for coupled Stokes and Darcy flows with floating Stokes domains

    NASA Astrophysics Data System (ADS)

    Wang, Changqing; Yotov, Ivan

    2013-11-01

    A non-overlapping domain decomposition method is presented to solve a coupled Stokes-Darcy flow problem in parallel by partitioning the computational domain into multiple subdomains. Specifically, in the case where floating Stokes subdomain occurs, an approach based on the FETI methods is introduced and tested.

  20. Structural basis for the regulation of enzymatic activity of Regnase-1 by domain-domain interactions

    PubMed Central

    Yokogawa, Mariko; Tsushima, Takashi; Noda, Nobuo N.; Kumeta, Hiroyuki; Enokizono, Yoshiaki; Yamashita, Kazuo; Standley, Daron M.; Takeuchi, Osamu; Akira, Shizuo; Inagaki, Fuyuhiko

    2016-01-01

    Regnase-1 is an RNase that directly cleaves mRNAs of inflammatory genes such as IL-6 and IL-12p40, and negatively regulates cellular inflammatory responses. Here, we report the structures of four domains of Regnase-1 from Mus musculus—the N-terminal domain (NTD), PilT N-terminus like (PIN) domain, zinc finger (ZF) domain and C-terminal domain (CTD). The PIN domain harbors the RNase catalytic center; however, it is insufficient for enzymatic activity. We found that the NTD associates with the PIN domain and significantly enhances its RNase activity. The PIN domain forms a head-to-tail oligomer and the dimer interface overlaps with the NTD binding site. Interestingly, mutations blocking PIN oligomerization had no RNase activity, indicating that both oligomerization and NTD binding are crucial for RNase activity in vitro. These results suggest that Regnase-1 RNase activity is tightly controlled by both intramolecular (NTD-PIN) and intermolecular (PIN-PIN) interactions. PMID:26927947

  1. Application of modern tensor calculus to engineered domain structures. 2. Tensor distinction of domain states.

    PubMed

    Kopský, Vojtech

    2006-03-01

    The theory of domain states is reviewed as a prerequisite for consideration of tensorial distinction of domain states. It is then shown that the parameters of the first domain in a ferroic phase transition from a set of isomorphic groups of the same oriented Laue class can be systematically and suitably represented in terms of typical variables. On replacing these variables by actual tensor components according to the previous paper, we can reveal the tensorial parameters associated with each particular symmetry descent. Parameters are distinguished by the ireps to which they belong and this can be used to determine which of them are the principal parameters that distinguish all domain states, in contrast to secondary parameters which are common to several domain states. In general, the parameters are expressed as the covariant components of the tensors. A general procedure is described which is designed to transform the results to Cartesian components. It consists of two parts: the first, called the labelling of covariants, and its inverse, called the conversion equations. Transformation of parameters from the first domain state to other states is now reduced to irreducible subspaces whose maximal dimension is three in contrast with higher dimensions of tensor spaces. With this method, we can explicitly calculate tensor parameters for all domain states. To find the distinction of pairs of domain states, it is suitable to use the concept of the twinning group which is briefly described. PMID:16489243

  2. Matter antimatter domains: A possible solution to the CP domain wall problem in the early universe

    NASA Technical Reports Server (NTRS)

    Mohanty, A. K.; Stecker, F. W.

    1984-01-01

    An SU(5) grand unified theory model is used to show how the degeneracy between vacua with different spontaneously broken charge parity can be dynamically lifted by a condensate of heavy fermion pairs. This drives a phase transition to a unique vacuum state with definite charge parity. The transition eliminates the domain walls in a matter antimatter symmetric domain cosmology.

  3. Intellectual Growth in Children as a Function of Domain Specific and Domain General Working Memory Subgroups

    ERIC Educational Resources Information Center

    Swanson, H. Lee

    2011-01-01

    This study examined whether children's growth on measures of fluid (Raven Colored Progressive Matrices) and crystallized (reading and math achievement) intelligence was attributable to domain-specific or domain-general functions of working memory (WM). A sample of 290 elementary school children was tested on measures of intelligence across three…

  4. [Development of domain specific search engines].

    PubMed

    Takai, T; Tokunaga, M; Maeda, K; Kaminuma, T

    2000-01-01

    As cyber space exploding in a pace that nobody has ever imagined, it becomes very important to search cyber space efficiently and effectively. One solution to this problem is search engines. Already a lot of commercial search engines have been put on the market. However these search engines respond with such cumbersome results that domain specific experts can not tolerate. Using a dedicate hardware and a commercial software called OpenText, we have tried to develop several domain specific search engines. These engines are for our institute's Web contents, drugs, chemical safety, endocrine disruptors, and emergent response for chemical hazard. These engines have been on our Web site for testing.

  5. On automating domain connectivity for overset grids

    NASA Technical Reports Server (NTRS)

    Chiu, Ing-Tsau

    1994-01-01

    An alternative method for domain connectivity among systems of overset grids is presented. Reference uniform Cartesian systems of points are used to achieve highly efficient domain connectivity, and form the basis for a future fully automated system. The Cartesian systems are used to approximated body surfaces and to map the computational space of component grids. By exploiting the characteristics of Cartesian Systems, Chimera type hole-cutting and identification of donor elements for intergrid boundary points can be carried out very efficiently. The method is tested for a range of geometrically complex multiple-body overset grid systems.

  6. Small domain-size multiblock copolymer electrolytes

    DOEpatents

    Pistorino, Jonathan; Eitouni, Hany Basam

    2016-09-20

    New block polymer electrolytes have been developed which have higher conductivities than previously reported for other block copolymer electrolytes. The new materials are constructed of multiple blocks (>5) of relatively low domain size. The small domain size provides greater protection against formation of dendrites during cycling against lithium in an electrochemical cell, while the large total molecular weight insures poor long range alignment, which leads to higher conductivity. In addition to higher conductivity, these materials can be more easily synthesized because of reduced requirements on the purity level of the reagents.

  7. Casimir forces in the time domain: Theory

    SciTech Connect

    Rodriguez, Alejandro W.; McCauley, Alexander P.; Joannopoulos, John D.; Johnson, Steven G.

    2009-07-15

    We present a method to compute Casimir forces in arbitrary geometries and for arbitrary materials based on the finite-difference time-domain (FDTD) scheme. The method involves the time evolution of electric and magnetic fields in response to a set of current sources, in a modified medium with frequency-independent conductivity. The advantage of this approach is that it allows one to exploit existing FDTD software, without modification, to compute Casimir forces. In this paper, we focus on the derivation, implementation choices, and essential properties of the time-domain algorithm, both considered analytically and illustrated in the simplest parallel-plate geometry.

  8. Anderson localization in the time domain

    NASA Astrophysics Data System (ADS)

    Sacha, Krzysztof; Delande, Dominique

    2016-08-01

    In analogy with the usual Anderson localization taking place in time-independent disordered quantum systems where the disorder acts in configuration space, systems exposed to temporally disordered potentials can display Anderson localization in the time domain. We demonstrate this phenomenon with one-dimensional examples where a temporally disordered potential induces localization during the quantum evolution of wave packets, in contrast with a fully delocalized classical dynamics. This is an example of a time crystal phenomenon, i.e., a crystalline behavior in the time domain.

  9. Time-domain Raman analytical forward solvers.

    PubMed

    Martelli, Fabrizio; Binzoni, Tiziano; Sekar, Sanathana Konugolu Venkata; Farina, Andrea; Cavalieri, Stefano; Pifferi, Antonio

    2016-09-01

    A set of time-domain analytical forward solvers for Raman signals detected from homogeneous diffusive media is presented. The time-domain solvers have been developed for two geometries: the parallelepiped and the finite cylinder. The potential presence of a background fluorescence emission, contaminating the Raman signal, has also been taken into account. All the solvers have been obtained as solutions of the time dependent diffusion equation. The validation of the solvers has been performed by means of comparisons with the results of "gold standard" Monte Carlo simulations. These forward solvers provide an accurate tool to explore the information content encoded in the time-resolved Raman measurements. PMID:27607645

  10. Standing gravitational waves from domain walls

    SciTech Connect

    Gogberashvili, Merab; Myrzakul, Shynaray; Singleton, Douglas

    2009-07-15

    We construct a plane symmetric, standing gravitational wave for a domain wall plus a massless scalar field. The scalar field can be associated with a fluid which has the properties of 'stiff' matter, i.e., matter in which the speed of sound equals the speed of light. Although domain walls are observationally ruled out in the present era, the solution has interesting features which might shed light on the character of exact nonlinear wave solutions to Einstein's equations. Additionally this solution may act as a template for higher dimensional 'brane-world' model standing waves.

  11. Nodal domains in open microwave systems.

    PubMed

    Kuhl, U; Höhmann, R; Stöckmann, H-J; Gnutzmann, S

    2007-03-01

    Nodal domains are studied both for real psiR and imaginary part psiI of the wave functions of an open microwave cavity and found to show the same behavior as wave functions in closed billiards. In addition we investigate the variation of the number of nodal domains and the signed area correlation by changing the global phase phig according to psiR+ipsiI=eiphig(psiR'+ipsiI'). This variation can be qualitatively, and the correlation quantitatively explained in terms of the phase rigidity characterizing the openness of the billiard.

  12. Nodal domains in open microwave systems

    NASA Astrophysics Data System (ADS)

    Kuhl, U.; Höhmann, R.; Stöckmann, H.-J.; Gnutzmann, S.

    2007-03-01

    Nodal domains are studied both for real ψR and imaginary part ψI of the wave functions of an open microwave cavity and found to show the same behavior as wave functions in closed billiards. In addition we investigate the variation of the number of nodal domains and the signed area correlation by changing the global phase φg according to ψR+iψI=eiφg(ψR'+iψI') . This variation can be qualitatively, and the correlation quantitatively explained in terms of the phase rigidity characterizing the openness of the billiard.

  13. Strategy for cloaking of twisted domains

    SciTech Connect

    Schmiele, Martin; Rockstuhl, Carsten; Lederer, Falk

    2009-05-15

    We describe a strategy to cloak twisted domains where, in contrast to the usual cloaks, the outer domain does not necessarily need to possess a direct connection to the point of inflation. The strategy consists of two steps. At first, a transformation is applied to untwist the geometry. Then, a second transformation is applied to create a point-transformed cloak with vanishing scattering cross section. As an extreme, yet analytical example, we construct a cloak having the shape of a spiral. Full-wave simulations confirm that electromagnetic waves impinging on the spiral-type cloak are bent around the structure with no discernible scattering.

  14. Convergence Analysis of a Domain Decomposition Paradigm

    SciTech Connect

    Bank, R E; Vassilevski, P S

    2006-06-12

    We describe a domain decomposition algorithm for use in several variants of the parallel adaptive meshing paradigm of Bank and Holst. This algorithm has low communication, makes extensive use of existing sequential solvers, and exploits in several important ways data generated as part of the adaptive meshing paradigm. We show that for an idealized version of the algorithm, the rate of convergence is independent of both the global problem size N and the number of subdomains p used in the domain decomposition partition. Numerical examples illustrate the effectiveness of the procedure.

  15. A non-chromatographic protein purification strategy using Src 3 homology domains as generalized capture domains.

    PubMed

    Kim, Heejae; Chen, Wilfred

    2016-09-20

    Protein purification using inverse phase transition of elastin-like polypeptide (ELP) domains is a useful alternative to chromatography. Genetic fusions of ELP domains to various proteins have the ability to reversibly transition between soluble monomers and micron-sized aggregates and this has been used to selectively purify many ELP fusions. Affinity domains can enhance this technology by using specific protein binding domains to enable ELP mediated affinity capture (EMAC) of proteins of interest (POI) that have been fused to corresponding affinity ligands. In this paper, we highlight the use of Src homology 3 (SH3) domains and corresponding peptide ligands in EMAC that have differential binding affinities towards SH3 for efficient capture and elution of proteins. Furthermore, differences between capture and elution of a monomeric and a multimeric protein were also studied. PMID:27457699

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

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

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

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

    PubMed Central

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

    2016-01-01

    The use of Fourier domain model observer is challenged by iterative reconstruction (IR), because IR algorithms are nonlinear and IR images have noise texture different from that of FBP. A modified Fourier domain model observer, which incorporates nonlinear noise and resolution properties, has been proposed for IR and needs to be validated with human detection performance. On the other hand, the spatial domain model observer is theoretically applicable to IR, but more computationally intensive than the Fourier domain method. The purpose of this study is to compare the modified Fourier domain model observer to the spatial domain model observer with both FBP and IR images, using human detection performance as the gold standard. A phantom with inserts of various low contrast levels and sizes was repeatedly scanned 100 times on a third-generation, dual-source CT scanner at 5 dose levels and reconstructed using FBP and IR algorithms. The human detection performance of the inserts was measured via a 2-alternative-forced-choice (2AFC) test. In addition, two model observer performances were calculated, including a Fourier domain non-prewhitening model observer and a spatial domain channelized Hotelling observer. The performance of these two mode observers was compared in terms of how well they correlated with human observer performance. Our results demonstrated that the spatial domain model observer correlated well with human observers across various dose levels, object contrast levels, and object sizes. The Fourier domain observer correlated well with human observers using FBP images, but overestimated the detection performance using IR images. PMID:27239086

  18. A PH domain in ACAP1 possesses key features of the BAR domain in promoting membrane curvature.

    PubMed

    Pang, Xiaoyun; Fan, Jun; Zhang, Yan; Zhang, Kai; Gao, Bingquan; Ma, Jun; Li, Jian; Deng, Yuchen; Zhou, Qiangjun; Egelman, Edward H; Hsu, Victor W; Sun, Fei

    2014-10-13

    The BAR (Bin-Amphiphysin-Rvs) domain undergoes dimerization to produce a curved protein structure, which superimposes onto membrane through electrostatic interactions to sense and impart membrane curvature. In some cases, a BAR domain also possesses an amphipathic helix that inserts into the membrane to induce curvature. ACAP1 (Arfgap with Coil coil, Ankyrin repeat, and PH domain protein 1) contains a BAR domain. Here, we show that this BAR domain can neither bind membrane nor impart curvature, but instead requires a neighboring PH (Pleckstrin Homology) domain to achieve these functions. Specific residues within the PH domain are responsible for both membrane binding and curvature generation. The BAR domain adjacent to the PH domain instead interacts with the BAR domains of neighboring ACAP1 proteins to enable clustering at the membrane. Thus, we have uncovered the molecular basis for an unexpected and unconventional collaboration between PH and BAR domains in membrane bending. PMID:25284369

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

    DOE PAGES

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

    2014-12-31

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

  20. Interaction of actin with carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) receptor in liposomes is Ca2+- and phospholipid-dependent.

    PubMed

    Lu, Rongze; Niesen, Michiel J M; Hu, Weidong; Vaidehi, Nagarajan; Shively, John E

    2011-08-01

    The regulation of binding of G-actin to cytoplasmic domains of cell surface receptors is a common mechanism to control diverse biological processes. To model the regulation of G-actin binding to a cell surface receptor we used the cell-cell adhesion molecule carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1-S) in which G-actin binds to its short cytoplasmic domain (12 amino acids; Chen, C. J., Kirshner, J., Sherman, M. A., Hu, W., Nguyen, T., and Shively, J. E. (2007) J. Biol. Chem. 282, 5749-5760). A liposome model system demonstrates that G-actin binds to the cytosolic domain peptide of CEACAM1-S in the presence of negatively charged palmitoyl-oleoyl phosphatidylserine (POPS) liposomes and Ca(2+). In contrast, no binding of G-actin was observed in palmitoyl-oleoyl phosphatidylcholine (POPC) liposomes or when a key residue in the peptide, Phe-454, is replaced with Ala. Molecular Dynamics simulations on CEACAM1-S in an asymmetric phospholipid bilayer show migration of Ca(2+) ions to the lipid leaflet containing POPS and reveal two conformations for Phe-454 explaining the reversible availability of this residue for G-actin binding. NMR transverse relaxation optimized spectroscopic analysis of (13)C-labeled Phe-454 CEACAM1-S peptide in liposomes plus actin further confirmed the existence of two peptide conformers and the Ca(2+) dependence of actin binding. These findings explain how a receptor with a short cytoplasmic domain can recruit a cytosolic protein in a phospholipid and Ca(2+)-specific manner. In addition, this model system provides a powerful approach that can be applied to study other membrane protein interactions with their cytosolic targets.

  1. Reporting Valid and Reliable Overall Scores and Domain Scores

    ERIC Educational Resources Information Center

    Yao, Lihua

    2010-01-01

    In educational assessment, overall scores obtained by simply averaging a number of domain scores are sometimes reported. However, simply averaging the domain scores ignores the fact that different domains have different score points, that scores from those domains are related, and that at different score points the relationship between overall…

  2. The Loyal Opposition Comments on Plan Domain Description Languages

    NASA Technical Reports Server (NTRS)

    Frank, Jeremy; Golden, Keith; Jonsson, Ari

    2003-01-01

    In this paper we take a critical look at PDDL 2.1 as designers and users of plan domain description languages. We describe planning domains that have features which are hard to model using PDDL 2.1. We then offer some suggestions on domain description language design, and describe how these suggestions make modeling our chosen domains easier.

  3. Conceptualizing Indicator Domains for Evaluating Action Research

    ERIC Educational Resources Information Center

    Piggot-Irvine, Eileen; Rowe, Wendy; Ferkins, Lesley

    2015-01-01

    The focus of this paper is to share thinking about meta-level evaluation of action research (AR), and to introduce indicator domains for assessing and measuring inputs, outputs and outcomes. Meta-level and multi-site evaluation has been rare in AR beyond project implementation and participant satisfaction. The paper is the first of several…

  4. Notes from Beyond the Cognitive Domain.

    ERIC Educational Resources Information Center

    Brand, Alice, G., Comp.; Graves, Dick, Comp.

    This collection of materials, a summary of a workshop, is in four parts. The first part lists participants in the workshop and their addresses. The second part presents a recorder's summary of statements made by six participants in a panel presentation on "What Is the Domain Beyond?" The third section gives brief accounts of three interactive…

  5. Time-Domain Simulation of RF Couplers

    SciTech Connect

    Smithe, David; Carlsson, Johan; Austin, Travis

    2009-11-26

    We have developed a finite-difference time-domain (FDTD) fluid-like approach to integrated plasma-and-coupler simulation [1], and show how it can be used to model LH and ICRF couplers in the MST and larger tokamaks.[2] This approach permits very accurate 3-D representation of coupler geometry, and easily includes non-axi-symmetry in vessel wall, magnetic equilibrium, and plasma density. The plasma is integrated with the FDTD Maxwell solver in an implicit solve that steps over electron time-scales, and permits tenuous plasma in the coupler itself, without any need to distinguish or interface between different regions of vacuum and/or plasma. The FDTD algorithm is also generalized to incorporate a time-domain sheath potential [3] on metal structures within the simulation, to look for situations where the sheath potential might generate local sputtering opportunities. Benchmarking of the time-domain sheath algorithm has been reported in the references. Finally, the time-domain software [4] permits the use of particles, either as field diagnostic (test particles) or to self-consistently compute plasma current from the applied RF power.

  6. Domain General Constraints on Statistical Learning

    ERIC Educational Resources Information Center

    Thiessen, Erik D.

    2011-01-01

    All theories of language development suggest that learning is constrained. However, theories differ on whether these constraints arise from language-specific processes or have domain-general origins such as the characteristics of human perception and information processing. The current experiments explored constraints on statistical learning of…

  7. fork head domain genes in zebrafish.

    PubMed

    Odenthal, J; Nüsslein-Volhard, C

    1998-07-01

    Nine members of the fork head domain gene family (fkd1-fkd9) were isolated from early cDNA libraries in the zebrafish. They show unique expression patterns in whole-mount RNA in situ hybridization during the first 24 h of embryonic development. These fkd genes fall into three of ten classes, based on sequence similarities within the DNA-binding domain, whereas members for the other seven classes described in other vertebrates were not found. In addition to conserved residues at certain positions in the fork head domain, characteristic transcription activation domains as well as similarities in expression patterns were found for members of the different classes. Members of class I (fkd1/axial, fkd2/Zffkh1, fkd4 and fkd7) are differentially transcribed in unsegmented dorsal axial structures such as the floor plate, the notochord, the hypochord and, in addition, the endoderm. Transcripts of fkd3 and fkd5 (class II) are mainly detected in the cells of the ectoderm which form neural tissues, as is the case for genes of this class in other species. RNAs of the three members of class V (fkd6, fkd8 and fkd9) are expressed in the paraxial mesoderm and transiently in the neuroectoderm. fkd6 is strongly expressed in neural crest cells from early stages on, whereas fkd2 and fkd7 are transcribed in individual neural crest cells in the pharyngula period.

  8. Scalable Domain Decomposed Monte Carlo Particle Transport

    SciTech Connect

    O'Brien, Matthew Joseph

    2013-12-05

    In this dissertation, we present the parallel algorithms necessary to run domain decomposed Monte Carlo particle transport on large numbers of processors (millions of processors). Previous algorithms were not scalable, and the parallel overhead became more computationally costly than the numerical simulation.

  9. Semi-supervised domain adaptation on manifolds.

    PubMed

    Cheng, Li; Pan, Sinno Jialin

    2014-12-01

    In real-life problems, the following semi-supervised domain adaptation scenario is often encountered: we have full access to some source data, which is usually very large; the target data distribution is under certain unknown transformation of the source data distribution; meanwhile, only a small fraction of the target instances come with labels. The goal is to learn a prediction model by incorporating information from the source domain that is able to generalize well on the target test instances. We consider an explicit form of transformation functions and especially linear transformations that maps examples from the source to the target domain, and we argue that by proper preprocessing of the data from both source and target domains, the feasible transformation functions can be characterized by a set of rotation matrices. This naturally leads to an optimization formulation under the special orthogonal group constraints. We present an iterative coordinate descent solver that is able to jointly learn the transformation as well as the model parameters, while the geodesic update ensures the manifold constraints are always satisfied. Our framework is sufficiently general to work with a variety of loss functions and prediction problems. Empirical evaluations on synthetic and real-world experiments demonstrate the competitive performance of our method with respect to the state-of-the-art. PMID:25314712

  10. Domain growth kinetics in stratifying foam films

    NASA Astrophysics Data System (ADS)

    Zhang, Yiran; Sharma, Vivek

    2015-11-01

    Baking bread, brewing cappuccino, pouring beer, washing dishes, shaving, shampooing, whipping eggs and blowing bubbles all involve creation of aqueous foam films. Typical foam films consist of two surfactant-laden surfaces that are ~ 5 nm - 10 micron apart. Sandwiched between these interfacial layers is a fluid that drains primarily under the influence of viscous and interfacial forces, including disjoining pressure. Interestingly, a layered ordering of micelles inside the foam films (thickness <100 nm) leads to a stepwise thinning phenomena called stratification, which results in a thickness-dependent variation in reflected light intensity, visualized as progressively darker shades of gray. Thinner, darker domains spontaneously grow within foam films. We show that the domain expansion dynamics exhibit two distinct growth regimes with characteristic scaling laws. Though several studies have focused on the expansion dynamics of isolated domains that exhibit a diffusion-like scaling, the change in expansion kinetics observed after domains contact with the Plateau border has not been reported and analyzed before.

  11. Physical Education's Fourth Domain: Physical Fitness

    ERIC Educational Resources Information Center

    Beaudet, Bob; Acquaviva, John

    2005-01-01

    The Surgeon General's report discusses the importance of daily physical activity and addresses the role of schools' physical education programs in implementing activity into every child's life. Professionals in the physical education field have typically used three domains to address the physical education curriculum: motor, cognitive, and…

  12. Development of sulfonamide AKT PH domain inhibitors

    PubMed Central

    Ahad, Ali Md.; Zuohe, Song; Du-Cuny, Lei; Moses, Sylvestor A.; Zhou, Li Li; Zhang, Shuxing; Powis, Garth; Meuillet, Emmanuelle J.; Mash, Eugene A.

    2011-01-01

    Disruption of the phosphatidylinositol 3-kinase/AKT signaling pathway can lead to apoptosis in cancer cells. Previously we identified a lead sulfonamide that selectively bound to the pleckstrin homology (PH) domain of AKT and induced apoptosis when present at low micromolar concentrations. To examine the effects of structural modification, a set of sulfonamides related to the lead compound was designed, synthesized, and tested for binding to the expressed PH domain of AKT using a surface plasmon resonance-based competitive binding assay. Cellular activity was determined by means of an assay for pAKT production and a cell killing assay using BxPC3 cells. The most active compounds in the set are lipophilic and possess an aliphatic chain of the proper length. Results were interpreted with the aid of computational modeling. This paper represents the first structure-activity relationship (SAR) study of a large family of AKT PH domain inhibitors. Information obtained will be used in the design of the next generation of inhibitors of AKT PH domain function. PMID:21353784

  13. Efficient integration method for fictitious domain approaches

    NASA Astrophysics Data System (ADS)

    Duczek, Sascha; Gabbert, Ulrich

    2015-10-01

    In the current article, we present an efficient and accurate numerical method for the integration of the system matrices in fictitious domain approaches such as the finite cell method (FCM). In the framework of the FCM, the physical domain is embedded in a geometrically larger domain of simple shape which is discretized using a regular Cartesian grid of cells. Therefore, a spacetree-based adaptive quadrature technique is normally deployed to resolve the geometry of the structure. Depending on the complexity of the structure under investigation this method accounts for most of the computational effort. To reduce the computational costs for computing the system matrices an efficient quadrature scheme based on the divergence theorem (Gauß-Ostrogradsky theorem) is proposed. Using this theorem the dimension of the integral is reduced by one, i.e. instead of solving the integral for the whole domain only its contour needs to be considered. In the current paper, we present the general principles of the integration method and its implementation. The results to several two-dimensional benchmark problems highlight its properties. The efficiency of the proposed method is compared to conventional spacetree-based integration techniques.

  14. Clarifying domains of internalizing psychopathology using neurophysiology.

    PubMed

    Vaidyanathan, U; Nelson, L D; Patrick, C J

    2012-03-01

    Current initiatives such as the National Institute of Mental Health's Research Domain Criteria project aim to reorganize classification of mental disorders along neurobiological lines. Here, we describe how consideration of findings from psychiatric research employing two physiological measures with distinct neural substrates--the startle blink reflex and the error-related negativity (ERN)--can help to clarify relations among disorders entailing salient anxiety or depressive symptomatology. Specifically, findings across various studies and reviews reveal distinct patterns of association for both the startle blink reflex and the ERN with three key domains of psychopathology: (1) Fear (or phobic) disorders (distinguished by increased startle to unpleasant stimuli, but normal-range ERN). (2) Non-phobic anxiety disorders and negative affect (associated with increased ERN, increased startle across all types of emotional stimuli and increased baseline startle) and, more tentatively (3) Major depression (for which patterns of response for both startle and ERN appear to vary, as a function of severity and distinct symptomatology). Findings from this review point to distinct neurobiological indicators of key psychopathology domains that have been previously demarcated using personality and diagnostic data. Notably, these indicators exhibit more specificity in their relations with these three domains than has been seen in quantitative-dimensional models. Implications of these findings are discussed. PMID:21854683

  15. Teachers' Domain Evaluation Report. CCT Reports

    ERIC Educational Resources Information Center

    Pasnik, Shelley; Keisch, Deborah

    2004-01-01

    This report is the result of a five-month study; it is comprised of two components: (1) an overview of the current knowledge base regarding how rich media resources, like Teachers' Domain, can support teaching and learning in K-12 schools; and (2) case studies of teachers, technology coordinators and administrators' perceptions and potential use…

  16. Domain Differences in Early Social Interactions

    ERIC Educational Resources Information Center

    Dahl, Audun; Campos, Joseph J.

    2013-01-01

    Different social experiences help children develop distinctions between domains of norms. This study investigated whether mothers respond differently to moral, prudential, and pragmatic norms during the 2nd year, a period that precedes the time when children are able to make explicit distinctions between these norms. Sixty mothers of infants…

  17. The dynamics of domain walls and strings

    NASA Technical Reports Server (NTRS)

    Gregory, Ruth; Haws, David; Garfinkle, David

    1989-01-01

    The leading order finite-width corrections to the equation of motion describing the motion of a domain wall are derived. The regime in which this equation of motion is invalid is discussed. Spherically and cylindrically symmetric solutions to this equation of motion are found. A misconception that has arisen in recent years regarding the rigidity (or otherwise) of cosmic strings is also clarified.

  18. Memetic Algorithms, Domain Knowledge, and Financial Investing

    ERIC Educational Resources Information Center

    Du, Jie

    2012-01-01

    While the question of how to use human knowledge to guide evolutionary search is long-recognized, much remains to be done to answer this question adequately. This dissertation aims to further answer this question by exploring the role of domain knowledge in evolutionary computation as applied to real-world, complex problems, such as financial…

  19. Simplified technique demonstrates magnetic domain switching

    NASA Technical Reports Server (NTRS)

    1967-01-01

    Light from a conventional photographic light source is polarized and projected through thin samples of gadolinium iron garnet and then observed with a conventional polarizing microscope. A distinctive change in color from red to yellow is observed as the magnetic domains are switched.

  20. Public Domain Microcomputer Software for Forestry.

    ERIC Educational Resources Information Center

    Martin, Les

    A project was conducted to develop a computer forestry/forest products bibliography applicable to high school and community college vocational/technical programs. The project director contacted curriculum clearinghouses, computer companies, and high school and community college instructors in order to obtain listings of public domain programs for…

  1. The Different Roles of Aggrecan Interaction Domains

    PubMed Central

    2012-01-01

    The aggregating proteoglycans of the lectican family are important components of extracellular matrices. Aggrecan is the most well studied of these and is central to cartilage biomechanical properties and skeletal development. Key to its biological function is the fixed charge of the many glycosaminoglycan chains, that provide the basis for the viscoelastic properties necessary for load distribution over the articular surface. This review is focused on the globular domains of aggrecan and their role in anchoring the proteoglycans to other extracellular matrix components. The N-terminal G1 domain is vital in that it binds the proteoglycan to hyaluronan in ternary complex with link protein, retaining the proteoglycan in the tissue. The importance of the C-terminal G3 domain interactions has recently been emphasized by two different human hereditary disorders: autosomal recessive aggrecan-type spondyloepimetaphyseal dysplasia and autosomal dominant familial osteochondritis dissecans. In these two conditions, different missense mutations in the aggrecan C-type lectin repeat have been described. The resulting amino acid replacements affect the ligand interactions of the G3 domain, albeit with widely different phenotypic outcomes. PMID:23019016

  2. Scalable Domain Decomposed Monte Carlo Particle Transport

    NASA Astrophysics Data System (ADS)

    O'Brien, Matthew Joseph

    In this dissertation, we present the parallel algorithms necessary to run domain decomposed Monte Carlo particle transport on large numbers of processors (millions of processors). Previous algorithms were not scalable, and the parallel overhead became more computationally costly than the numerical simulation. The main algorithms we consider are: • Domain decomposition of constructive solid geometry: enables extremely large calculations in which the background geometry is too large to fit in the memory of a single computational node. • Load Balancing: keeps the workload per processor as even as possible so the calculation runs efficiently. • Global Particle Find: if particles are on the wrong processor, globally resolve their locations to the correct processor based on particle coordinate and background domain. • Visualizing constructive solid geometry, sourcing particles, deciding that particle streaming communication is completed and spatial redecomposition. These algorithms are some of the most important parallel algorithms required for domain decomposed Monte Carlo particle transport. We demonstrate that our previous algorithms were not scalable, prove that our new algorithms are scalable, and run some of the algorithms up to 2 million MPI processes on the Sequoia supercomputer.

  3. The Fourth Domain of Educational Objectives: Induction.

    ERIC Educational Resources Information Center

    Holleman, Wes

    1985-01-01

    Tests the claim to comprehensiveness of Bloom's taxonomy of educational objectives by analyzing educational objectives of some freshmen orientation programs and those connected with human developmental tasks. It is concluded that the taxonomy should be enlarged with a fourth domain: actual induction into tasks for which students are being…

  4. Nucleic acids encoding a cellulose binding domain

    DOEpatents

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

    1996-03-05

    A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques. 15 figs.

  5. Nucleic acids encoding a cellulose binding domain

    DOEpatents

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

    1996-01-01

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

  6. Adaptive Random Testing with Combinatorial Input Domain

    PubMed Central

    Lu, Yansheng

    2014-01-01

    Random testing (RT) is a fundamental testing technique to assess software reliability, by simply selecting test cases in a random manner from the whole input domain. As an enhancement of RT, adaptive random testing (ART) has better failure-detection capability and has been widely applied in different scenarios, such as numerical programs, some object-oriented programs, and mobile applications. However, not much work has been done on the effectiveness of ART for the programs with combinatorial input domain (i.e., the set of categorical data). To extend the ideas to the testing for combinatorial input domain, we have adopted different similarity measures that are widely used for categorical data in data mining and have proposed two similarity measures based on interaction coverage. Then, we propose a new version named ART-CID as an extension of ART in combinatorial input domain, which selects an element from categorical data as the next test case such that it has the lowest similarity against already generated test cases. Experimental results show that ART-CID generally performs better than RT, with respect to different evaluation metrics. PMID:24772036

  7. An English language interface for constrained domains

    NASA Technical Reports Server (NTRS)

    Page, Brenda J.

    1989-01-01

    The Multi-Satellite Operations Control Center (MSOCC) Jargon Interpreter (MJI) demonstrates an English language interface for a constrained domain. A constrained domain is defined as one with a small and well delineated set of actions and objects. The set of actions chosen for the MJI is from the domain of MSOCC Applications Executive (MAE) Systems Test and Operations Language (STOL) directives and contains directives for signing a cathode ray tube (CRT) on or off, calling up or clearing a display page, starting or stopping a procedure, and controlling history recording. The set of objects chosen consists of CRTs, display pages, STOL procedures, and history files. Translation from English sentences to STOL directives is done in two phases. In the first phase, an augmented transition net (ATN) parser and dictionary are used for determining grammatically correct parsings of input sentences. In the second phase, grammatically typed sentences are submitted to a forward-chaining rule-based system for interpretation and translation into equivalent MAE STOL directives. Tests of the MJI show that it is able to translate individual clearly stated sentences into the subset of directives selected for the prototype. This approach to an English language interface may be used for similarly constrained situations by modifying the MJI's dictionary and rules to reflect the change of domain.

  8. Developing Domain Ontologies for Course Content

    ERIC Educational Resources Information Center

    Boyce, Sinead; Pahl, Claus

    2007-01-01

    Ontologies have the potential to play an important role in instructional design and the development of course content. They can be used to represent knowledge about content, supporting instructors in creating content or learners in accessing content in a knowledge-guided way. While ontologies exist for many subject domains, their quality and…

  9. Factor Score Reliabilities and Domain Validities.

    ERIC Educational Resources Information Center

    Gorsuch, Richard L.

    1980-01-01

    Kaiser and Michael reported a formula for factor scores giving an internal consistency reliability and its square root, the domain validity. Using this formula is inappropriate if variables are included which have trival weights rather than salient weights for the factor for which the score is being computed. (Author/RL)

  10. Kernel Manifold Alignment for Domain Adaptation.

    PubMed

    Tuia, Devis; Camps-Valls, Gustau

    2016-01-01

    The wealth of sensory data coming from different modalities has opened numerous opportunities for data analysis. The data are of increasing volume, complexity and dimensionality, thus calling for new methodological innovations towards multimodal data processing. However, multimodal architectures must rely on models able to adapt to changes in the data distribution. Differences in the density functions can be due to changes in acquisition conditions (pose, illumination), sensors characteristics (number of channels, resolution) or different views (e.g. street level vs. aerial views of a same building). We call these different acquisition modes domains, and refer to the adaptation problem as domain adaptation. In this paper, instead of adapting the trained models themselves, we alternatively focus on finding mappings of the data sources into a common, semantically meaningful, representation domain. This field of manifold alignment extends traditional techniques in statistics such as canonical correlation analysis (CCA) to deal with nonlinear adaptation and possibly non-corresponding data pairs between the domains. We introduce a kernel method for manifold alignment (KEMA) that can match an arbitrary number of data sources without needing corresponding pairs, just few labeled examples in all domains. KEMA has interesting properties: 1) it generalizes other manifold alignment methods, 2) it can align manifolds of very different complexities, performing a discriminative alignment preserving each manifold inner structure, 3) it can define a domain-specific metric to cope with multimodal specificities, 4) it can align data spaces of different dimensionality, 5) it is robust to strong nonlinear feature deformations, and 6) it is closed-form invertible, which allows transfer across-domains and data synthesis. To authors' knowledge this is the first method addressing all these important issues at once. We also present a reduced-rank version of KEMA for computational

  11. Kernel Manifold Alignment for Domain Adaptation

    PubMed Central

    Tuia, Devis; Camps-Valls, Gustau

    2016-01-01

    The wealth of sensory data coming from different modalities has opened numerous opportunities for data analysis. The data are of increasing volume, complexity and dimensionality, thus calling for new methodological innovations towards multimodal data processing. However, multimodal architectures must rely on models able to adapt to changes in the data distribution. Differences in the density functions can be due to changes in acquisition conditions (pose, illumination), sensors characteristics (number of channels, resolution) or different views (e.g. street level vs. aerial views of a same building). We call these different acquisition modes domains, and refer to the adaptation problem as domain adaptation. In this paper, instead of adapting the trained models themselves, we alternatively focus on finding mappings of the data sources into a common, semantically meaningful, representation domain. This field of manifold alignment extends traditional techniques in statistics such as canonical correlation analysis (CCA) to deal with nonlinear adaptation and possibly non-corresponding data pairs between the domains. We introduce a kernel method for manifold alignment (KEMA) that can match an arbitrary number of data sources without needing corresponding pairs, just few labeled examples in all domains. KEMA has interesting properties: 1) it generalizes other manifold alignment methods, 2) it can align manifolds of very different complexities, performing a discriminative alignment preserving each manifold inner structure, 3) it can define a domain-specific metric to cope with multimodal specificities, 4) it can align data spaces of different dimensionality, 5) it is robust to strong nonlinear feature deformations, and 6) it is closed-form invertible, which allows transfer across-domains and data synthesis. To authors’ knowledge this is the first method addressing all these important issues at once. We also present a reduced-rank version of KEMA for computational

  12. Phase Transitions and Domain Structures in Nanoferroelectrics.

    NASA Astrophysics Data System (ADS)

    Levanyuk, Arkadi

    2006-03-01

    A review of the Landau-type theory of size effects in ferroelectric phase transitions will be presented. An aspect of this theory, a question about the ``critical thickness'' of ferroelectric thin films will be the main emphasis. This question can be reduced to that of the size dependence of temperature of ferroelectric phase transition by taking into account two possibilities for such a transition: formation of (i) single- or (ii) multi-domain ferroelectric state. In a defect-free sample, two factors would define which of these possibilities is realized: the depolarizing field and the specific features of the sample surface reflected in the boundary conditions for the Landau-type equations in addition to the conventional electrodynamics boundary conditions. The possibility of the transition into the single domain state strongly depends on a character of electrodes and the additional boundary conditions, while it is much less important for the multi-domain case. In realistic conditions, the transition would proceed into the multi-domain state, especially in near cubic ferroelectrics, e.g. films of cubic perovskites with an elastic mismatch between the film and a substrate. Importantly, the shift of a transition temperature with respect to a bulk is relatively small in this case. The message is that, while studying the question about the ``critical thickness'', multi-domain states rather than single domain ones should be considered first of all, contrary to the approach in some recent papers where only monodomain state was studied.. In particular, there is no definite indication of ultimate ``critical thickness'' for a multi domain ferroelectric state in nearly cubic samples. Along with ultra thin films the ferroelectric nanopowders are also intensively studied now. Here the size effects are more complicated because of long-range interaction between the particles. The problems which the theory faces here are briefly commented upon. It is worth mentioning that

  13. Comparison of frequency-domain and time-domain rotorcraft vibration control methods

    NASA Technical Reports Server (NTRS)

    Gupta, N. K.

    1984-01-01

    Active control of rotor-induced vibration in rotorcraft has received significant attention recently. Two classes of techniques have been proposed. The more developed approach works with harmonic analysis of measured time histories and is called the frequency-domain approach. The more recent approach computes the control input directly using the measured time history data and is called the time-domain approach. The report summarizes the results of a theoretical investigation to compare the two approaches. Five specific areas were addressed: (1) techniques to derive models needed for control design (system identification methods), (2) robustness with respect to errors, (3) transient response, (4) susceptibility to noise, and (5) implementation difficulties. The system identification methods are more difficult for the time-domain models. The time-domain approach is more robust (e.g., has higher gain and phase margins) than the frequency-domain approach. It might thus be possible to avoid doing real-time system identification in the time-domain approach by storing models at a number of flight conditions. The most significant error source is the variation in open-loop vibrations caused by pilot inputs, maneuvers or gusts. The implementation requirements are similar except that the time-domain approach can be much simpler to implement if real-time system identification were not necessary.

  14. PTEN-PDZ domain interactions: binding of PTEN to PDZ domains of PTPN13.

    PubMed

    Sotelo, Natalia S; Schepens, Jan T G; Valiente, Miguel; Hendriks, Wiljan J A J; Pulido, Rafael

    2015-05-01

    Protein modular interactions mediated by PDZ domains are essential for the establishment of functional protein networks controlling diverse cellular functions. The tumor suppressor PTEN possesses a C-terminal PDZ-binding motif (PDZ-BM) that is recognized by a specific set of PDZ domains from scaffolding and regulatory proteins. Here, we review the current knowledge on PTEN-PDZ domain interactions and tumor suppressor networks, describe methodology suitable to analyze these interactions, and report the binding of PTEN and the PDZ domain-containing protein tyrosine phosphatase PTPN13. Yeast two-hybrid and GST pull-down analyses showed that PTEN binds to PDZ2/PTPN13 domain in a manner that depends on the specific PTPN13 PDZ domain arrangement involving the interdomain region between PDZ1 and PDZ2. Furthermore, a specific binding profile of PTEN to PDZ2/PTPN13 domain was observed by mutational analysis of the PTEN PDZ-BM. Our results disclose a PDZ-mediated physical interaction of PTEN and PTPN13 with potential relevance in tumor suppression and cell homeostasis.

  15. Domain fusion analysis by applying relational algebra to protein sequence and domain databases

    PubMed Central

    Truong, Kevin; Ikura, Mitsuhiko

    2003-01-01

    Background Domain fusion analysis is a useful method to predict functionally linked proteins that may be involved in direct protein-protein interactions or in the same metabolic or signaling pathway. As separate domain databases like BLOCKS, PROSITE, Pfam, SMART, PRINTS-S, ProDom, TIGRFAMs, and amalgamated domain databases like InterPro continue to grow in size and quality, a computational method to perform domain fusion analysis that leverages on these efforts will become increasingly powerful. Results This paper proposes a computational method employing relational algebra to find domain fusions in protein sequence databases. The feasibility of this method was illustrated on the SWISS-PROT+TrEMBL sequence database using domain predictions from the Pfam HMM (hidden Markov model) database. We identified 235 and 189 putative functionally linked protein partners in H. sapiens and S. cerevisiae, respectively. From scientific literature, we were able to confirm many of these functional linkages, while the remainder offer testable experimental hypothesis. Results can be viewed at . Conclusion As the analysis can be computed quickly on any relational database that supports standard SQL (structured query language), it can be dynamically updated along with the sequence and domain databases, thereby improving the quality of predictions over time. PMID:12734020

  16. Crystal structure of domain-swapped STE20 OSR1 kinase domain

    SciTech Connect

    Lee, Seung-Jae; Cobb, Melanie H.; Goldsmith, Elizabeth J.

    2009-09-15

    OSR1 (oxidative stress-responsive-1) and SPAK (Ste20/Sps1-related proline/alanine-rich kinase) belong to the GCK-VI subfamily of Ste20 group kinases. OSR1 and SPAK are key regulators of NKCCs (Na{sup +}/K{sup +}/2Cl{sup -} cotransporters) and activated by WNK family members (with-no-lysine kinase), mutations of which are known to cause Gordon syndrome, an autosomal dominant form of inherited hypertension. The crystal structure of OSR1 kinase domain has been solved at 2.25 {angstrom}. OSR1 forms a domain-swapped dimer in an inactive conformation, in which P+1 loop and {alpha}EF helix are swapped between dimer-related monomers. Structural alignment with nonswapped Ste20 TAO2 kinase indicates that the integrity of chemical interactions in the kinase domain is well preserved in the domain-swapped interfaces. The OSR1 kinase domain has now been added to a growing list of domain-swapped protein kinases recently reported, suggesting that the domain-swapping event provides an additional layer of complexity in regulating protein kinase activity.

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

    PubMed Central

    Culbertson, Jennifer; Kirby, Simon

    2016-01-01

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

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

    PubMed

    Culbertson, Jennifer; Kirby, Simon

    2015-01-01

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

  19. The acidic domains of the Toc159 chloroplast preprotein receptor family are intrinsically disordered protein domains

    PubMed Central

    2009-01-01

    Background The Toc159 family of proteins serve as receptors for chloroplast-destined preproteins. They directly bind to transit peptides, and exhibit preprotein substrate selectivity conferred by an unknown mechanism. The Toc159 receptors each include three domains: C-terminal membrane, central GTPase, and N-terminal acidic (A-) domains. Although the function(s) of the A-domain remains largely unknown, the amino acid sequences are most variable within these domains, suggesting they may contribute to the functional specificity of the receptors. Results The physicochemical properties of the A-domains are characteristic of intrinsically disordered proteins (IDPs). Using CD spectroscopy we show that the A-domains of two Arabidopsis Toc159 family members (atToc132 and atToc159) are disordered at physiological pH and temperature and undergo conformational changes at temperature and pH extremes that are characteristic of IDPs. Conclusions Identification of the A-domains as IDPs will be important for determining their precise function(s), and suggests a role in protein-protein interactions, which may explain how these proteins serve as receptors for such a wide variety of preprotein substrates. PMID:20042108

  20. REvolver: modeling sequence evolution under domain constraints.

    PubMed

    Koestler, Tina; von Haeseler, Arndt; Ebersberger, Ingo

    2012-09-01

    Simulating the change of protein sequences over time in a biologically realistic way is fundamental for a broad range of studies with a focus on evolution. It is, thus, problematic that typically simulators evolve individual sites of a sequence identically and independently. More realistic simulations are possible; however, they are often prohibited by limited knowledge concerning site-specific evolutionary constraints or functional dependencies between amino acids. As a consequence, a protein's functional and structural characteristics are rapidly lost in the course of simulated evolution. Here, we present REvolver (www.cibiv.at/software/revolver), a program that simulates protein sequence alteration such that evolutionarily stable sequence characteristics, like functional domains, are maintained. For this purpose, REvolver recruits profile hidden Markov models (pHMMs) for parameterizing site-specific models of sequence evolution in an automated fashion. pHMMs derived from alignments of homologous proteins or protein domains capture information regarding which sequence sites remained conserved over time and where in a sequence insertions or deletions are more likely to occur. Thus, they describe constraints on the evolutionary process acting on these sequences. To demonstrate the performance of REvolver as well as its applicability in large-scale simulation studies, we evolved the entire human proteome up to 1.5 expected substitutions per site. Simultaneously, we analyzed the preservation of Pfam and SMART domains in the simulated sequences over time. REvolver preserved 92% of the Pfam domains originally present in the human sequences. This value drops to 15% when traditional models of amino acid sequence evolution are used. Thus, REvolver represents a significant advance toward a realistic simulation of protein sequence evolution on a proteome-wide scale. Further, REvolver facilitates the simulation of a protein family with a user-defined domain architecture at

  1. Architecture and function of metallopeptidase catalytic domains

    PubMed Central

    Cerdà-Costa, Núria; Gomis-Rüth, Francesc Xavier

    2014-01-01

    The cleavage of peptide bonds by metallopeptidases (MPs) is essential for life. These ubiquitous enzymes participate in all major physiological processes, and so their deregulation leads to diseases ranging from cancer and metastasis, inflammation, and microbial infection to neurological insults and cardiovascular disorders. MPs cleave their substrates without a covalent intermediate in a single-step reaction involving a solvent molecule, a general base/acid, and a mono-or dinuclear catalytic metal site. Most monometallic MPs comprise a short metal-binding motif (HEXXH), which includes two metal-binding histidines and a general base/acid glutamate, and they are grouped into the zincin tribe of MPs. The latter divides mainly into the gluzincin and metzincin clans. Metzincins consist of globular ∼130–270-residue catalytic domains, which are usually preceded by N-terminal pro-segments, typically required for folding and latency maintenance. The catalytic domains are often followed by C-terminal domains for substrate recognition and other protein–protein interactions, anchoring to membranes, oligomerization, and compartmentalization. Metzincin catalytic domains consist of a structurally conserved N-terminal subdomain spanning a five-stranded β-sheet, a backing helix, and an active-site helix. The latter contains most of the metal-binding motif, which is here characteristically extended to HEXXHXXGXX(H,D). Downstream C-terminal subdomains are generally shorter, differ more among metzincins, and mainly share a conserved loop—the Met-turn—and a C-terminal helix. The accumulated structural data from more than 300 deposited structures of the 12 currently characterized metzincin families reviewed here provide detailed knowledge of the molecular features of their catalytic domains, help in our understanding of their working mechanisms, and form the basis for the design of novel drugs. PMID:24596965

  2. ECOD: An Evolutionary Classification of Protein Domains

    PubMed Central

    Kinch, Lisa N.; Pei, Jimin; Shi, Shuoyong; Kim, Bong-Hyun; Grishin, Nick V.

    2014-01-01

    Understanding the evolution of a protein, including both close and distant relationships, often reveals insight into its structure and function. Fast and easy access to such up-to-date information facilitates research. We have developed a hierarchical evolutionary classification of all proteins with experimentally determined spatial structures, and presented it as an interactive and updatable online database. ECOD (Evolutionary Classification of protein Domains) is distinct from other structural classifications in that it groups domains primarily by evolutionary relationships (homology), rather than topology (or “fold”). This distinction highlights cases of homology between domains of differing topology to aid in understanding of protein structure evolution. ECOD uniquely emphasizes distantly related homologs that are difficult to detect, and thus catalogs the largest number of evolutionary links among structural domain classifications. Placing distant homologs together underscores the ancestral similarities of these proteins and draws attention to the most important regions of sequence and structure, as well as conserved functional sites. ECOD also recognizes closer sequence-based relationships between protein domains. Currently, approximately 100,000 protein structures are classified in ECOD into 9,000 sequence families clustered into close to 2,000 evolutionary groups. The classification is assisted by an automated pipeline that quickly and consistently classifies weekly releases of PDB structures and allows for continual updates. This synchronization with PDB uniquely distinguishes ECOD among all protein classifications. Finally, we present several case studies of homologous proteins not recorded in other classifications, illustrating the potential of how ECOD can be used to further biological and evolutionary studies. PMID:25474468

  3. A mixed finite element domain decomposition method for nearly elastic wave equations in the frequency domain

    SciTech Connect

    Feng, Xiaobing

    1996-12-31

    A non-overlapping domain decomposition iterative method is proposed and analyzed for mixed finite element methods for a sequence of noncoercive elliptic systems with radiation boundary conditions. These differential systems describe the motion of a nearly elastic solid in the frequency domain. The convergence of the iterative procedure is demonstrated and the rate of convergence is derived for the case when the domain is decomposed into subdomains in which each subdomain consists of an individual element associated with the mixed finite elements. The hybridization of mixed finite element methods plays a important role in the construction of the discrete procedure.

  4. Phylogenetic Analysis of Brassica rapa MATH-Domain Proteins.

    PubMed

    Zhao, Liming; Huang, Yong; Hu, Yan; He, Xiaoli; Shen, Wenhui; Liu, Chunlin; Ruan, Ying

    2013-05-01

    The MATH (meprin and TRAF-C homology) domain is a fold of seven anti-parallel β-helices involved in protein-protein interaction. Here, we report the identification and characterization of 90 MATH-domain proteins from the Brassica rapa genome. By sequence analysis together with MATH-domain proteins from other species, the B. rapa MATH-domain proteins can be grouped into 6 classes. Class-I protein has one or several MATH domains without any other recognizable domain; Class-II protein contains a MATH domain together with a conserved BTB (Broad Complex, Tramtrack, and Bric-a-Brac ) domain; Class-III protein belongs to the MATH/Filament domain family; Class-IV protein contains a MATH domain frequently combined with some other domains; Class-V protein has a relative long sequence but contains only one MATH domain; Class-VI protein is characterized by the presence of Peptidase and UBQ (Ubiquitinylation) domains together with one MATH domain. As part of our study regarding seed development of B. rapa, six genes are screened by SSH (Suppression Subtractive Hybridization) and their expression levels are analyzed in combination with seed developmental stages, and expression patterns suggested that Bra001786, Bra03578 and Bra036572 may be seed development specific genes, while Bra001787, Bra020541 and Bra040904 may be involved in seed and flower organ development. This study provides the first characterization of the MATH domain proteins in B. rapa.

  5. The BTB domains of the potassium channel tetramerization domain proteins prevalently assume pentameric states.

    PubMed

    Smaldone, Giovanni; Pirone, Luciano; Pedone, Emilia; Marlovits, Thomas; Vitagliano, Luigi; Ciccarelli, Luciano

    2016-06-01

    Potassium channel tetramerization domain-containing (KCTD) proteins are involved in fundamental physio-pathological processes. Here, we report an analysis of the oligomeric state of the Bric-à-brack, Tram-track, Broad complex (BTB) domains of seven distinct KCTDs belonging to five major clades of the family evolution tree. Despite their functional and sequence variability, present electron microscopy data highlight the occurrence of well-defined pentameric states for all domains. Our data also show that these states coexist with alternative forms which include open pentamers. Thermal denaturation analyses conducted using KCTD1 as a model suggest that, in these proteins, different domains cooperate to their overall stability. Finally, negative-stain electron micrographs of KCTD6(BTB) in complex with Cullin3 show the presence of assemblies with a five-pointed pinwheel shape. PMID:27152988

  6. Study of ferroelectric domain switching by domain wall induced light scattering

    NASA Astrophysics Data System (ADS)

    Volk, T.; Isakov, D.; Ivanov, N.; Ivleva, L.; Betzler, K.; Tunyagi, A.; Wöhlecke, M.

    2005-04-01

    The 90°-light scattering on domain walls was probed in various strontium barium niobate (SBN) crystals for studies of the ferroelectric switching under pulsed fields. The validity of this optical method is proved by a good agreement of the switching parameters deduced from optical scattering data with those obtained with electric methods. Scanning of the scattering over the crystal bulk revealed local specialities of the switching, particularly, a marked distribution of the domain wall density D along the polar axis with a maximum close to the negative electrode. In compliance with these in situ observations, the electro-optic coefficient rc reveals a position dependence in all SBN crystals poled in the ferroelectric phase, rc decreasing from the positive to negative electrode. This regularity is interpreted in terms of the domain density distribution D(z ) and accounted for by an asymmetry of the domain nucleation.

  7. Repeated evolution of identical domain architecture in metazoan netrin domain-containing proteins.

    PubMed

    Leclère, Lucas; Rentzsch, Fabian

    2012-01-01

    The majority of proteins in eukaryotes are composed of multiple domains, and the number and order of these domains is an important determinant of protein function. Although multidomain proteins with a particular domain architecture were initially considered to have a common evolutionary origin, recent comparative studies of protein families or whole genomes have reported that a minority of multidomain proteins could have appeared multiple times independently. Here, we test this scenario in detail for the signaling molecules netrin and secreted frizzled-related proteins (sFRPs), two groups of netrin domain-containing proteins with essential roles in animal development. Our primary phylogenetic analyses suggest that the particular domain architectures of each of these proteins were present in the eumetazoan ancestor and evolved a second time independently within the metazoan lineage from laminin and frizzled proteins, respectively. Using an array of phylogenetic methods, statistical tests, and character sorting analyses, we show that the polyphyly of netrin and sFRP is well supported and cannot be explained by classical phylogenetic reconstruction artifacts. Despite their independent origins, the two groups of netrins and of sFRPs have the same protein interaction partners (Deleted in Colorectal Cancer/neogenin and Unc5 for netrins and Wnts for sFRPs) and similar developmental functions. Thus, these cases of convergent evolution emphasize the importance of domain architecture for protein function by uncoupling shared domain architecture from shared evolutionary history. Therefore, we propose the terms merology to describe the repeated evolution of proteins with similar domain architecture and discuss the potential of merologous proteins to help understanding protein evolution. PMID:22813778

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

    SciTech Connect

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

    2014-12-31

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

  9. Ribosomal small subunit domains radiate from a central core

    PubMed Central

    Gulen, Burak; Petrov, Anton S.; Okafor, C. Denise; Vander Wood, Drew; O’Neill, Eric B.; Hud, Nicholas V.; Williams, Loren Dean

    2016-01-01

    The domain architecture of a large RNA can help explain and/or predict folding, function, biogenesis and evolution. We offer a formal and general definition of an RNA domain and use that definition to experimentally characterize the rRNA of the ribosomal small subunit. Here the rRNA comprising a domain is compact, with a self-contained system of molecular interactions. A given rRNA helix or stem-loop must be allocated uniquely to a single domain. Local changes such as mutations can give domain-wide effects. Helices within a domain have interdependent orientations, stabilities and interactions. With these criteria we identify a core domain (domain A) of small subunit rRNA. Domain A acts as a hub, linking the four peripheral domains and imposing orientational and positional restraints on the other domains. Experimental characterization of isolated domain A, and mutations and truncations of it, by methods including selective 2′OH acylation analyzed by primer extension and circular dichroism spectroscopy are consistent with our architectural model. The results support the utility of the concept of an RNA domain. Domain A, which exhibits structural similarity to tRNA, appears to be an essential core of the small ribosomal subunit. PMID:26876483

  10. Purification and Structural Analysis of LEM-Domain Proteins.

    PubMed

    Herrada, Isaline; Bourgeois, Benjamin; Samson, Camille; Buendia, Brigitte; Worman, Howard J; Zinn-Justin, Sophie

    2016-01-01

    LAP2-emerin-MAN1 (LEM)-domain proteins are modular proteins characterized by the presence of a conserved motif of about 50 residues. Most LEM-domain proteins localize at the inner nuclear membrane, but some are also found in the endoplasmic reticulum or nuclear interior. Their architecture has been analyzed by predicting the limits of their globular domains, determining the 3D structure of these domains and in a few cases calculating the 3D structure of specific domains bound to biological targets. The LEM domain adopts an α-helical fold also found in SAP and HeH domains of prokaryotes and unicellular eukaryotes. The LEM domain binds to BAF (barrier-to-autointegration factor; BANF1), which interacts with DNA and tethers chromatin to the nuclear envelope. LAP2 isoforms also share an N-terminal LEM-like domain, which binds DNA. The structure and function of other globular domains that distinguish LEM-domain proteins from each other have been characterized, including the C-terminal dimerization domain of LAP2α and C-terminal WH and UHM domains of MAN1. LEM-domain proteins also have large intrinsically disordered regions that are involved in intra- and intermolecular interactions and are highly regulated by posttranslational modifications in vivo.

  11. Ribosomal small subunit domains radiate from a central core

    NASA Astrophysics Data System (ADS)

    Gulen, Burak; Petrov, Anton S.; Okafor, C. Denise; Vander Wood, Drew; O'Neill, Eric B.; Hud, Nicholas V.; Williams, Loren Dean

    2016-02-01

    The domain architecture of a large RNA can help explain and/or predict folding, function, biogenesis and evolution. We offer a formal and general definition of an RNA domain and use that definition to experimentally characterize the rRNA of the ribosomal small subunit. Here the rRNA comprising a domain is compact, with a self-contained system of molecular interactions. A given rRNA helix or stem-loop must be allocated uniquely to a single domain. Local changes such as mutations can give domain-wide effects. Helices within a domain have interdependent orientations, stabilities and interactions. With these criteria we identify a core domain (domain A) of small subunit rRNA. Domain A acts as a hub, linking the four peripheral domains and imposing orientational and positional restraints on the other domains. Experimental characterization of isolated domain A, and mutations and truncations of it, by methods including selective 2‧OH acylation analyzed by primer extension and circular dichroism spectroscopy are consistent with our architectural model. The results support the utility of the concept of an RNA domain. Domain A, which exhibits structural similarity to tRNA, appears to be an essential core of the small ribosomal subunit.

  12. Ribosomal small subunit domains radiate from a central core.

    PubMed

    Gulen, Burak; Petrov, Anton S; Okafor, C Denise; Vander Wood, Drew; O'Neill, Eric B; Hud, Nicholas V; Williams, Loren Dean

    2016-02-15

    The domain architecture of a large RNA can help explain and/or predict folding, function, biogenesis and evolution. We offer a formal and general definition of an RNA domain and use that definition to experimentally characterize the rRNA of the ribosomal small subunit. Here the rRNA comprising a domain is compact, with a self-contained system of molecular interactions. A given rRNA helix or stem-loop must be allocated uniquely to a single domain. Local changes such as mutations can give domain-wide effects. Helices within a domain have interdependent orientations, stabilities and interactions. With these criteria we identify a core domain (domain A) of small subunit rRNA. Domain A acts as a hub, linking the four peripheral domains and imposing orientational and positional restraints on the other domains. Experimental characterization of isolated domain A, and mutations and truncations of it, by methods including selective 2'OH acylation analyzed by primer extension and circular dichroism spectroscopy are consistent with our architectural model. The results support the utility of the concept of an RNA domain. Domain A, which exhibits structural similarity to tRNA, appears to be an essential core of the small ribosomal subunit.

  13. Skyrmion domain wall collision and domain wall-gated skyrmion logic

    NASA Astrophysics Data System (ADS)

    Xing, Xiangjun; Pong, Philip W. T.; Zhou, Yan

    2016-08-01

    Skyrmions and domain walls are significant spin textures of great technological relevance to magnetic memory and logic applications, where they can be used as carriers of information. The unique topology of skyrmions makes them display emergent dynamical properties as compared with domain walls. Some studies have demonstrated that the two topologically inequivalent magnetic objects could be interconverted by using cleverly designed geometric structures. Here, we numerically address the skyrmion domain wall collision in a magnetic racetrack by introducing relative motion between the two objects based on a specially designed junction. An electric current serves as the driving force that moves a skyrmion toward a trapped domain wall pair. We see different types of collision dynamics depending on the driving parameters. Most importantly, the modulation of skyrmion transport using domain walls is realized in this system, allowing a set of domain wall-gated logical NOT, NAND, and NOR gates to be constructed. This work provides a skyrmion-based spin-logic architecture that is fully compatible with racetrack memories.

  14. Domain view: a web tool for protein domain visualization and analysis.

    PubMed

    Pan, Xiaokang; Bingman, Craig A; Wesenberg, Gary E; Sun, Zhaohui; Phillips, George N

    2010-12-01

    The identification of sequence-based protein domains and their boundaries is often a prelude to structure determination. An accurate prediction of disordered regions, secondary structures and low complexity segments of target protein sequences can improve the efficiency of selection in structural genomics and also aid in design of constructs for directed structural biology studies. At the Center for Eukaryotic Structural Genomics (CESG) we have developed DomainView, a web tool to visualize and analyze predicted protein domains, disordered regions, secondary structures and low complexity segments of target protein sequences for selection of experimental protein structure attempts. DomainView consists of a relational database and a web graphical-user interface. The database was developed based on MySQL, which stores data from target protein sequences and their domains, disordered regions, secondary structures and low complexity segments. The program of the web user interface is a Perl CGI script. When a user searches for a target protein sequence, the script displays the combinational information about the domains and other features of that target sequence graphically on a web page by querying the database. The graphical representation for each feature is linked to a web page showing more detailed annotation information or to a new window directly running the corresponding prediction program to show further information about that feature.

  15. Parallel computation of a domain decomposition method

    SciTech Connect

    Chin, R.C.Y.; Hedstrom, G.W.; Scroggs, J.S.; Sorensen, D.C.

    1987-01-01

    The most easily tractable multiple scale problems are those in which there are only a small number of widely separated groups of scales and the motion on the fastest scales has little influence on the smooth part of the solution. An identifying feature of this class is the presence of regions in which the solution undergoes rapid variation. Such regions are called boundary or internal layers, depending on whether they are located near a boundary or in the interior of the domain. These are the problems which are most natural for multitasking because it makes sense to break up the domain according to the regions of different local behavior. This paper restricts its attention to this class of multiple scale problems.

  16. Student Reasoning Across Domains of Context

    NASA Astrophysics Data System (ADS)

    Warnakulasooriya, Rasil; Bao, Lei

    2001-10-01

    Students' learning and understanding of physical concepts depend on the context settings in which the concepts are introduced. In this research, questions were developed to investigate students' understanding of a wide range of physical concepts and how these were carried across different context domains. We conducted surveys and interviews with students in an algebra-based course on electricity and magnetism at The Ohio State University. The results show that students often apply their knowledge of physical principles inconsistently across context domains. For example, students who show understanding of the Newton's third law in a classical mechanics setting fail to recognize the same concept in the context of electricity and magnetism. Ref: L. Bao and E.F. Redish, "Model Analysis: Assessing the Dynamics of Student Learning." Submitted to Cognition and Instruction (2001). This work is supported in part by NSF grant REC-0087788

  17. LOB Domain Proteins: Beyond Lateral Organ Boundaries.

    PubMed

    Xu, Changzheng; Luo, Feng; Hochholdinger, Frank

    2016-02-01

    LATERAL ORGAN BOUNDARIES DOMAIN (LBD) proteins defined by a conserved LATERAL ORGAN BOUNDARIES (LOB) domain are key regulators of plant organ development. Recent studies have expanded their functional diversity beyond the definition of lateral organ boundaries to pollen development, plant regeneration, photomorphogenesis, pathogen response, and specific developmental functions in non-model plants, such as poplar and legumes. The identification of a range of upstream regulators, protein partners, and downstream targets of LBD family members has unraveled the molecular networks of LBD-dependent processes. Moreover, it has been demonstrated that LBD proteins have essential roles in integrating developmental changes in response to phytohormone signaling or environmental cues. As we discuss here, these novel discoveries of LBD functions and their molecular contexts promote a better understanding of this plant-specific transcription factor family. PMID:26616195

  18. Entropy gives rise to topologically associating domains

    PubMed Central

    Vasquez, Paula A.; Hult, Caitlin; Adalsteinsson, David; Lawrimore, Josh; Forest, Mark G.; Bloom, Kerry

    2016-01-01

    We investigate chromosome organization within the nucleus using polymer models whose formulation is closely guided by experiments in live yeast cells. We employ bead-spring chromosome models together with loop formation within the chains and the presence of nuclear bodies to quantify the extent to which these mechanisms shape the topological landscape in the interphase nucleus. By investigating the genome as a dynamical system, we show that domains of high chromosomal interactions can arise solely from the polymeric nature of the chromosome arms due to entropic interactions and nuclear confinement. In this view, the role of bio-chemical related processes is to modulate and extend the duration of the interacting domains. PMID:27257057

  19. Myonuclear domains in muscle adaptation and disease

    NASA Technical Reports Server (NTRS)

    Allen, D. L.; Roy, R. R.; Edgerton, V. R.

    1999-01-01

    Adult skeletal muscle fibers are among the few cell types that are truly multinucleated. Recently, evidence has accumulated supporting a role for the modulation of myonuclear number during muscle remodeling in response to injury, adaptation, and disease. These studies have demonstrated that muscle hypertrophy is associated with, and is dependent on, the addition of newly formed myonuclei via the fusion of myogenic cells to the adult myofiber, whereas muscle atrophy and disease appear to be associated with the loss of myonuclei, possibly through apoptotic-like mechanisms. Moreover, these studies also have demonstrated that myonuclear domain size, i. e., the amount of cytoplasm per myonucleus, is unchanged following the acute phase of hypertrophy but is reduced following atrophy. Together these data demonstrate that modulation of myonuclear number or myonuclear domain size (or both) is a mechanism contributing to the remodeling of adult skeletal muscle in response to alterations in the level of normal neuromuscular activity. Copyright 1999 John Wiley & Sons, Inc.

  20. Membrane Domain Formation on Nanostructured Scaffolds

    NASA Astrophysics Data System (ADS)

    Collier, Charles; Liu, Fangjie; Srijanto, Bernadeta

    The spatial organization of lipids and proteins in biological membranes seems to have a functional role in the life of a cell. Separation of the lipids into distinct domains of greater order and anchoring to the cytoskeleton are two main mechanisms for organizing the membrane in cells. We propose a novel model membrane consisting of a lipid bilayer suspended over a nanostructured scaffold consisting of arrays of fabricated nanopillars. Unlike traditional model membranes, our model will have well-defined lateral structure and distributed substrate attachments that will emulate the connections of cellular membranes to the underlying cytoskeleton. Membranes will be characterized using neutron reflectometry, atomic force microscopy and fluorescence to verify a suspended, planar geometry with restricted diffusion at suspension points, and free diffusion in between. This architecture will allow the controlled study of lipid domain reorganization, viral infection and signal transduction that depend on the lateral structure of the membrane.

  1. Diastereomeric liquid crystal domains at the mesoscale.

    PubMed

    Chen, Dong; Tuchband, Michael R; Horanyi, Balazs; Korblova, Eva; Walba, David M; Glaser, Matthew A; Maclennan, Joseph E; Clark, Noel A

    2015-08-07

    In many technologies used to achieve separation of enantiomers, chiral selectors are designed to display differential affinity for the two enantiomers of a chiral compound. Such complexes are diastereomeric, differing in structure and free energy for the two enantiomers and enabling chiral discrimination. Here we present evidence for strong diastereomeric interaction effects at the mesoscale, manifested in chiral liquid crystal guest materials confined in a chiral, nanoporous network of semi-crystalline helical nanofilaments. The nanoporous host is itself an assembly of achiral, bent-core liquid crystal molecules that phase-separate into a conglomerate of 100 micron-scale, helical nanofilament domains that differ in structure only in the handedness of their homogeneous chirality. With the inclusion of a homochiral guest liquid crystal, these enantiomeric domains become diastereomeric, exhibiting unexpected and markedly different mesoscale structures and orientation transitions producing optical effects in which chirality has a dominant role.

  2. Diastereomeric liquid crystal domains at the mesoscale

    NASA Astrophysics Data System (ADS)

    Chen, Dong; Tuchband, Michael R.; Horanyi, Balazs; Korblova, Eva; Walba, David M.; Glaser, Matthew A.; Maclennan, Joseph E.; Clark, Noel A.

    2015-08-01

    In many technologies used to achieve separation of enantiomers, chiral selectors are designed to display differential affinity for the two enantiomers of a chiral compound. Such complexes are diastereomeric, differing in structure and free energy for the two enantiomers and enabling chiral discrimination. Here we present evidence for strong diastereomeric interaction effects at the mesoscale, manifested in chiral liquid crystal guest materials confined in a chiral, nanoporous network of semi-crystalline helical nanofilaments. The nanoporous host is itself an assembly of achiral, bent-core liquid crystal molecules that phase-separate into a conglomerate of 100 micron-scale, helical nanofilament domains that differ in structure only in the handedness of their homogeneous chirality. With the inclusion of a homochiral guest liquid crystal, these enantiomeric domains become diastereomeric, exhibiting unexpected and markedly different mesoscale structures and orientation transitions producing optical effects in which chirality has a dominant role.

  3. Domain Growth Kinetics in Stratifying Foam Films

    NASA Astrophysics Data System (ADS)

    Zhang, Yiran; Sharma, Vivek

    2015-03-01

    Baking bread, brewing cappuccino, pouring beer, washing dishes, shaving, shampooing, whipping eggs and blowing bubbles all involve creation of aqueous foam films. Typical foam films consist of two surfactant-laden surfaces that are μ 5 nm - 10 micron apart. Sandwiched between these interfacial layers is a fluid that drains primarily under the influence of viscous and interfacial forces, including disjoining pressure. Interestingly, for certain low molecular weight surfactants, a layered ordering of micelles inside the foam films (thickness <100 nm) leads to a stepwise thinning phenomena called stratification. We experimentally elucidate the influence of these different driving forces, and confinement on drainage kinetics of horizontal stratifying foam films. Thinner, darker domains spontaneously grow within foam films. Quantitative characterization of domain growth visualized in a using Scheludko-type thin film cell and a theoretical model based on lubrication analysis, provide critical insights into hydrodynamics of thin foam films, and the strength and nature of surface forces, including supramolecular oscillatory structural forces.

  4. Entropy gives rise to topologically associating domains.

    PubMed

    Vasquez, Paula A; Hult, Caitlin; Adalsteinsson, David; Lawrimore, Josh; Forest, Mark G; Bloom, Kerry

    2016-07-01

    We investigate chromosome organization within the nucleus using polymer models whose formulation is closely guided by experiments in live yeast cells. We employ bead-spring chromosome models together with loop formation within the chains and the presence of nuclear bodies to quantify the extent to which these mechanisms shape the topological landscape in the interphase nucleus. By investigating the genome as a dynamical system, we show that domains of high chromosomal interactions can arise solely from the polymeric nature of the chromosome arms due to entropic interactions and nuclear confinement. In this view, the role of bio-chemical related processes is to modulate and extend the duration of the interacting domains. PMID:27257057

  5. Myosin flexibility: structural domains and collective vibrations.

    PubMed

    Navizet, Isabelle; Lavery, Richard; Jernigan, Robert L

    2004-02-15

    The movement of the myosin motor along an actin filament involves a directed conformational change within the cross-bridge formed between the protein and the filament. Despite the structural data that has been obtained on this system, little is known of the mechanics of this conformational change. We have used existing crystallographic structures of three conformations of the myosin head, containing the motor domain and the lever arm, for structural comparisons and mechanical studies with a coarse-grained elastic network model. The results enable us to define structurally conserved domains within the protein and to better understand myosin flexibility. Notably they point to the role of the light chains in rigidifying the lever arm and to changes in flexibility as a consequence of nucleotide binding.

  6. LHC RF System Time-Domain Simulation

    SciTech Connect

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

    2010-09-14

    Non-linear time-domain simulations have been developed for the Positron-Electron Project (PEP-II) and the Large Hadron Collider (LHC). These simulations capture the dynamic behavior of the RF station-beam interaction and are structured to reproduce the technical characteristics of the system (noise contributions, non-linear elements, and more). As such, they provide useful results and insight for the development and design of future LLRF feedback systems. They are also a valuable tool for the study of diverse longitudinal beam dynamics effects such as coupled-bunch impedance driven instabilities and single bunch longitudinal emittance growth. Results from these studies and related measurements from PEP-II and LHC have been presented in multiple places. This report presents an example of the time-domain simulation implementation for the LHC.

  7. An intelligent tutor for the space domain

    NASA Technical Reports Server (NTRS)

    Swigger, Kathleen; Loveland, Harry

    1987-01-01

    An intelligent tutoring system for the space domain is described. This system was developed on a Xerox 1108 using LOOPS and provides an environment for discovering principles of ground tracks as a direct function of the orbital elements. Some of the more practical design and implementation issues associated with the development of intelligent tutoring systems are examined. Some solutions to the problems and some suggestions for future research are offered.

  8. Domain decomposition methods for mortar finite elements

    SciTech Connect

    Widlund, O.

    1996-12-31

    In the last few years, domain decomposition methods, previously developed and tested for standard finite element methods and elliptic problems, have been extended and modified to work for mortar and other nonconforming finite element methods. A survey will be given of work carried out jointly with Yves Achdou, Mario Casarin, Maksymilian Dryja and Yvon Maday. Results on the p- and h-p-version finite elements will also be discussed.

  9. Keeping children healthy--the intermediate domain.

    PubMed

    Mayall, B

    1993-01-01

    This paper draws on two recent research studies to consider negotiations and relationships between parents and health staff as regards child health care and child rearing, to which each side contributes. The value of the concept of an intermediate domain, located between the public world of paid work and the private world of the family is explored to throw light on the character of these negotiations and relationships. The implications of gender for relationships between parent and health staff are considered.

  10. Domain-wall supergravities from sphere reduction

    NASA Astrophysics Data System (ADS)

    Cvetič , M.; Liu, James T.; Lü, H.; Pope, C. N.

    1999-10-01

    Kaluza-Klein sphere reductions of supergravities that admit Ads × Sphere vacuum solutions are believed to be consistent. The examples include the S4 and S7 reductions of eleven-dimensional supergravity, and the S5 reduction of ten-dimensional type IIB supergravity . In this paper we provide evidence that sphere reductions of supergravities that admit instead Domain-wallxSphere vacuum solutions are also consistent, where the background can be viewed as the near-horizon structure of a dilatonic p-brane of the theory. The resulting lower-dimensional theory is a gauged supergravity that admits a domain wall, rather than AdS, as a vacuum solution. We illustrate this consistency by taking the singular limits of certain modulus parameters, for which the original Sn compactifying spheres ( n = 4, 5 or 7) becomes Sp × Rq, with p = n - q < n. The consistency of the S4, S7 reductions then implies the consistency of the S p reductions of the lower-dimensional supergravities. In particular, we obtain explicit non-linear ansätze for the S3 reduction of type IIA and heterotic supergravities, restricting to the U(1) 2 subgroup of the SO(4) gauge group of S3. We also study the black-hole solutions in the lower-dimensional gauged supergravities with domain-wall backgrounds. We find new domain-wall black holes which are not the singular-modulus limits of the AdS black holes of the original theories, and we obtain their Killing spinors.

  11. Domain decomposition multigrid for unstructured grids

    SciTech Connect

    Shapira, Yair

    1997-01-01

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

  12. Working memory storage is intrinsically domain specific.

    PubMed

    Fougnie, Daryl; Zughni, Samir; Godwin, Douglass; Marois, René

    2015-02-01

    A longstanding debate in working memory (WM) is whether information is maintained in a central, capacity-limited storage system or whether there are domain-specific stores for different modalities. This question is typically addressed by determining whether concurrent storage of 2 different memory arrays produces interference. Prior studies using this approach have shown at least some cost to maintaining 2 memory arrays that differed in perceptual modalities. However, it is not clear whether these WM costs resulted from competition for a central, capacity-limited store or from other potential sources of dual-task interference, such as task preparation and coordination, overlap in representational content (e.g., object vs. space based), or cognitive strategies (e.g., verbalization, chunking of the stimulus material in a higher order structure). In the present study we assess dual-task costs during the concurrent performance of a visuospatial WM task and an auditory object WM task when such sources of interference are minimized. The results show that performance of these 2 WM tasks are independent from each another, even at high WM load. Only when we introduced a common representational format (spatial information) to both WM tasks did dual-task performance begin to suffer. These results are inconsistent with the notion of a domain-independent storage system, and suggest instead that WM is constrained by multiple domain-specific stores and central executive processes. Evidently, there is nothing intrinsic about the functional architecture of the human mind that prevents it from storing 2 distinct representations in WM, as long as these representations do not overlap in any functional domain.

  13. Metrology for terahertz time-domain spectrometers

    NASA Astrophysics Data System (ADS)

    Molloy, John F.; Naftaly, Mira

    2015-12-01

    In recent years the terahertz time-domain spectrometer (THz TDS) [1] has emerged as a key measurement device for spectroscopic investigations in the frequency range of 0.1-5 THz. To date, almost every type of material has been studied using THz TDS, including semiconductors, ceramics, polymers, metal films, liquid crystals, glasses, pharmaceuticals, DNA molecules, proteins, gases, composites, foams, oils, and many others. Measurements with a TDS are made in the time domain; conversion from the time domain data to a frequency spectrum is achieved by applying the Fourier Transform, calculated numerically using the Fast Fourier Transform (FFT) algorithm. As in many other types of spectrometer, THz TDS requires that the sample data be referenced to similarly acquired data with no sample present. Unlike frequency-domain spectrometers which detect light intensity and measure absorption spectra, a TDS records both amplitude and phase information, and therefore yields both the absorption coefficient and the refractive index of the sample material. The analysis of the data from THz TDS relies on the assumptions that: a) the frequency scale is accurate; b) the measurement of THz field amplitude is linear; and c) that the presence of the sample does not affect the performance characteristics of the instrument. The frequency scale of a THz TDS is derived from the displacement of the delay line; via FFT, positioning errors may give rise to frequency errors that are difficult to quantify. The measurement of the field amplitude in a THz TDS is required to be linear with a dynamic range of the order of 10 000. And attention must be given to the sample positioning and handling in order to avoid sample-related errors.

  14. Networked Ontologies from the Fisheries Domain

    NASA Astrophysics Data System (ADS)

    Caracciolo, Caterina; Heguiabehere, Juan; Sini, Margherita; Keizer, Johannes

    In this paper we report on ongoing work concerning the creation of a network of ontologies based on metadata for time series relative to the domain of fisheries, and hint at the possibility of exploiting the network for web service applications. The results obtained so far show that the reengineering of classification systems stored as relational databases is possible, although some technical problems is still to be addressed.

  15. Geophysical Signatures of Adjoining Lithospheric Domains

    NASA Astrophysics Data System (ADS)

    Gradmann, S.; Kaiser, J.

    2014-12-01

    Lithospheres of different age have distinctly different characteristics regarding their composition, thermal and density structure. Major differences exist between cratons and the Phanerozoic domains and mobile belts. We here investigate how the lateral transition from one lithospheric domain to another is reflected in the geophysical signatures, the seismic velocities, gravity, topography and geoid. We combine geophysical-petrological forward modeling with a comparison to worldwide occurrences of adjoining lithospheric domains. Three distinctly different mantle types (Archean, Proterozoic, Phanerozoic) are used to calculate the geophysical signatures of a range of possible lateral transition zones. The mantle types are characterized by their different elemental composition, from which stable mineral phases and bulk physical properties are derived. Usually, older SCLM (sub-lithospheric mantle) is more depleted in heavier minerals and thereby lighter, but this effect is mainly counterbalanced by the increased density caused by long-term thermal cooling. At the edges of cratons, changes in the thermal structure affect this balance. A range of models is tested for the effects of lateral variations in the crustal and SCLM structure (thickness, smoothness of thickness changes) and mantle compositions. Abrupt changes in composition and lithosphere thickness generally cause distinct topographic lows or ridges. In the real world, these may be offset by respective adjustments in Moho depth, crustal structure or sediment infill. Gradual variations in lithosphere thickness, however, only show minor geophysical signatures. A possible expression of adjoining lithospheric domains is the Scandinavian Mountain Belt in Norway at the edge of Proterozoic Baltica. Although many of the present-day topographic features are unlikely to have existed since the Precambrian, the evolution of the cratons (rejuvenation of the craton edges) may have assisted in shaping the present

  16. Dynamic Domains in Data Production Planning

    NASA Technical Reports Server (NTRS)

    Golden, Keith; Pang, Wanlin

    2005-01-01

    This paper discusses a planner-based approach to automating data production tasks, such as producing fire forecasts from satellite imagery and weather station data. Since the set of available data products is large, dynamic and mostly unknown, planning techniques developed for closed worlds are unsuitable. We discuss a number of techniques we have developed to cope with data production domains, including a novel constraint propagation algorithm based on planning graphs and a constraint-based approach to interleaved planning, sensing and execution.

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

    SciTech Connect

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

    2013-09-25

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

  18. Conservation and specialization in PAS domain dynamics.

    PubMed

    Pandini, A; Bonati, L

    2005-03-01

    The PAS (Per-ARNT-Sim) superfamily is presented as a well-suited study case to demonstrate how comparison of functional motions among distant homologous proteins with conserved fold characteristics may give insight into their functional specialization. Based on the importance of structural flexibility of the receptive structures in anticipating the signal-induced conformational changes of these sensory systems, the dynamics of these structures were analysed. Molecular dynamics was proved to be an effective method to obtain a reliable picture of the dynamics of the crystal structures of HERG, phy3, PYP and FixL, provided that an extensive conformational space sampling is performed. Other reliable sources of dynamic information were the ensembles of NMR structures of hPASK, HIF-2alpha and PYP. Essential dynamics analysis was successfully employed to extract the relevant information from the sampled conformational spaces. Comparison of motion patterns in the essential subspaces, based on the structural alignment, allowed identification of the specialized region in each domain. This appears to be evolved in the superfamily by following a specific trend, that also suggests the presence of a limited number of general solutions adopted by the PAS domains to sense external signals. These findings may give insight into unknown mechanisms of PAS domains and guide further experimental studies. PMID:15820977

  19. Masked object registration in the Fourier domain.

    PubMed

    Padfield, Dirk

    2012-05-01

    Registration is one of the most common tasks of image analysis and computer vision applications. The requirements of most registration algorithms include large capture range and fast computation so that the algorithms are robust to different scenarios and can be computed in a reasonable amount of time. For these purposes, registration in the Fourier domain using normalized cross-correlation is well suited and has been extensively studied in the literature. Another common requirement is masking, which is necessary for applications where certain regions of the image that would adversely affect the registration result should be ignored. To address these requirements, we have derived a mathematical model that describes an exact form for embedding the masking step fully into the Fourier domain so that all steps of translation registration can be computed efficiently using Fast Fourier Transforms. We provide algorithms and implementation details that demonstrate the correctness of our derivations. We also demonstrate how this masked FFT registration approach can be applied to improve the Fourier-Mellin algorithm that calculates translation, rotation, and scale in the Fourier domain. We demonstrate the computational efficiency, advantages, and correctness of our algorithm on a number of images from real-world applications. Our framework enables fast, global, parameter-free registration of images with masked regions.

  20. Linking in domain-swapped protein dimers

    PubMed Central

    Baiesi, Marco; Orlandini, Enzo; Trovato, Antonio; Seno, Flavio

    2016-01-01

    The presence of knots has been observed in a small fraction of single-domain proteins and related to their thermodynamic and kinetic properties. The exchanging of identical structural elements, typical of domain-swapped proteins, makes such dimers suitable candidates to validate the possibility that mutual entanglement between chains may play a similar role for protein complexes. We suggest that such entanglement is captured by the linking number. This represents, for two closed curves, the number of times that each curve winds around the other. We show that closing the curves is not necessary, as a novel parameter G′, termed Gaussian entanglement, is strongly correlated with the linking number. Based on 110 non redundant domain-swapped dimers, our analysis evidences a high fraction of chains with a significant intertwining, that is with |G′| > 1. We report that Nature promotes configurations with negative mutual entanglement and surprisingly, it seems to suppress intertwining in long protein dimers. Supported by numerical simulations of dimer dissociation, our results provide a novel topology-based classification of protein-swapped dimers together with some preliminary evidence of its impact on their physical and biological properties. PMID:27659606

  1. Time domain scattering of travelling wave radiance

    NASA Astrophysics Data System (ADS)

    Berger, Henry; Rand, Robert S.

    2002-12-01

    I present, apparently, a new description of radiative transfer problems in the time domain. It appears that for the first time a simple physical picture emerges of the underlying essence of scattered radiance when dealing with isotropic axially-symmetric scattering in nonconservative linear media as attenuated travelling waves was by analogy. The method used a new differential equation approach. Initially its accuracy in the frequency domain was demonstrated by applying it to a solved problem, where in the literature it is dealt with using the conventional 95-year-old integro-differential equation description. Confidence in the differential equation method was bolstered by showing how this new method produces the same analytical answer. The new technique converts the integro-differential equation formulation of radiative transfer into a "pure" differential equation formulation, consisting here in a mixture of ordinary and partial derivatives, and solves that. This paper analyzes the situation in the time domain using the differential equation description and again yields a travelling wave description. However, this time it is not simply by analogy that such a description is obtained. It is exact. This result of attenuated travelling waves was demonstrated in a prior paper by solving the integro-differential equation for the classic problem of axially-symmetric scalar isotropic scattering in a nonconservative linear medium. In this paper we revisit the problem, this time solving it by the differential equation method and obtain the identical result, once again confirming the method.

  2. Motor Domain Phosphorylation Modulates Kinesin-1 Transport*

    PubMed Central

    DeBerg, Hannah A.; Blehm, Benjamin H.; Sheung, Janet; Thompson, Andrew R.; Bookwalter, Carol S.; Torabi, Seyed F.; Schroer, Trina A.; Berger, Christopher L.; Lu, Yi; Trybus, Kathleen M.; Selvin, Paul R.

    2013-01-01

    Disruptions in microtubule motor transport are associated with a variety of neurodegenerative diseases. Post-translational modification of the cargo-binding domain of the light and heavy chains of kinesin has been shown to regulate transport, but less is known about how modifications of the motor domain affect transport. Here we report on the effects of phosphorylation of a mammalian kinesin motor domain by the kinase JNK3 at a conserved serine residue (Ser-175 in the B isoform and Ser-176 in the A and C isoforms). Phosphorylation of this residue has been implicated in Huntington disease, but the mechanism by which Ser-175 phosphorylation affects transport is unclear. The ATPase, microtubule-binding affinity, and processivity are unchanged between a phosphomimetic S175D and a nonphosphorylatable S175A construct. However, we find that application of force differentiates between the two. Placement of negative charge at Ser-175, through phosphorylation or mutation, leads to a lower stall force and decreased velocity under a load of 1 piconewton or greater. Sedimentation velocity experiments also show that addition of a negative charge at Ser-175 favors the autoinhibited conformation of kinesin. These observations imply that when cargo is transported by both dynein and phosphorylated kinesin, a common occurrence in the cell, there may be a bias that favors motion toward the minus-end of microtubules. Such bias could be used to tune transport in healthy cells when properly regulated but contribute to a disease state when misregulated. PMID:24072715

  3. Interactions between domain walls and spin currents

    NASA Astrophysics Data System (ADS)

    Klaui, M.; Laufenberg, M.; Backes, D.; Buhrer, W.; Rudiger, U.; Vila, L.; Vouille, C.; Faini, G.

    2006-03-01

    A promising novel approach for switching magnetic nanostructures is current-induced domain wall propagation (CIDP), where due to a spin torque effect, electrons transfer angular momentum to a head-to-head domain wall and thereby push it in the direction of the electron flow without any externally applied fields. This effect has been observed with a variety of techniques including MFM [1] and spin polarized scanning electron microscopy [2] to directly observe current-induced domain wall propagation in ferromagnetic nanostructures and magnetoresistance measurements to systematically probe the critical current densities as a function of the geometry [3]. The observed wall velocities and critical current densities, where wall motion sets in at room temperature, do not agree well with theoretical 0K calculations [4]. We have therefore measured the critical current densities as a function of the sample temperature. We find that the spin torque effect becomes more efficient at low temperatures, which could account for some of the observed discrepancies between the 300K experiment and the 0K simulation. [1] A. Yamaguchi et al., Phys. Rev. Lett. 92, 77205 (2004); [2] M. Klaui et al., PRL 95, 26601 (2005); [3] M. Klaui et al., PRL 94, 106601 (2005); [4] A. Thiaville et al., EPL 69, 990 (2005); G. Tatara et al., APL 86, 252509 (2005);

  4. MBT domain proteins in development and disease

    PubMed Central

    Bonasio, Roberto; Lecona, Emilio; Reinberg, Danny

    2013-01-01

    The Malignant Brain Tumor (MBT) domain is a “chromatin reader”, a protein module that binds to post-translational modifications on histone tails that are thought to affect a variety of chromatin processes, including transcription. More specifically, MBT domains recognize mono- and di-methylated lysines at a number of different positions on histone H3 and H4 tails. Three Drosophila proteins, SCM, L(3)MBT and SFMBT contain multiple adjacent MBT repeats and have critical roles in development, maintenance of cell identity, and tumor suppression. Although they function in different pathways, these proteins all localize to chromatin in vivo and repress transcription by a currently unknown molecular mechanism that requires the MBT domains. The human genome contains several homologues of these MBT proteins, some of which have been linked to important gene regulatory pathways, such as E2F/Rb- and Polycomb-mediated repression, and to the insurgence of certain neurological tumors. Here, we review the genetics, biochemistry, and cell biology of MBT proteins and their role in development and disease. PMID:19778625

  5. Birdsong dialect patterns explained using magnetic domains.

    PubMed

    Burridge, James; Kenney, Steven

    2016-06-01

    The songs and calls of many bird species, like human speech, form distinct regional dialects. We suggest that the process of dialect formation is analogous to the physical process of magnetic domain formation. We take the coastal breeding grounds of the Puget Sound white crowned sparrow as an example. Previous field studies suggest that birds of this species learn multiple songs early in life, and when establishing a territory for the first time, retain one of these dialects in order to match the majority of their neighbors. We introduce a simple lattice model of the process, showing that this matching behavior can produce single dialect domains provided the death rate of adult birds is sufficiently low. We relate death rate to thermodynamic temperature in magnetic materials, and calculate the critical death rate by analogy with the Ising model. Using parameters consistent with the known behavior of these birds we show that coastal dialect domain shapes may be explained by viewing them as low-temperature "stripe states."

  6. Domain wall motion in ferroelectrics: Barkhausen noise

    NASA Astrophysics Data System (ADS)

    Shur, V.; Rumyantsev, E.; Kozhevnikov, V.; Nikolaeva, E.; Shishkin, E.

    2002-03-01

    The switching current noise has been recorded during polarization reversal in single-crystalline gadolinium molybdate (GMO) and lithium tantalate (LT). Analysis of Barkhausen noise (BN) data allows to classify the noise types by determination of the critical indexes and fractal dimensions. BN is manifested as the short pulses during the polarization reversal. We have analyzed the BN data recorded in GMO and LT with various types of controlled domain structure. The data treatment in terms of probability distribution of duration, area and energy of individual pulses reveals the critical behavior typical for the fractal records in time. We used the Fourier transform and Hurst's rescaled range analysis for obtaining the Hurst factor, fractal dimension and classifying the noise types. We investigated by computer simulation the mechanism of sideways motion of 180O domain wall by nucleation at the wall taking into account the nuclei-nuclei interaction. It was shown that the moving domain walls display the fractal shape and their motion is accompanied by Flicker noise, which is in accord with experimental data. The research was made possible in part by Programs "Basic Research in Russian Universities" and "Priority Research in High School. Electronics", by Grant No. 01-02-17443 of RFBR, by Award No.REC-005 of CRDF.

  7. Time-Domain Filtering of Metasurfaces

    PubMed Central

    Wakatsuchi, Hiroki

    2015-01-01

    In general electromagnetic response of each material to a continuous wave does not vary in time domain if the frequency component remains the same. Recently, it turned out that integrating several circuit elements including schottky diodes with periodically metallised surfaces, or the so-called metasurfaces, leads to selectively absorbing specific types of waveforms or pulse widths even at the same frequency. These waveform-selective metasurfaces effectively showed different absorbing performances for different widths of pulsed sine waves by gradually varying their electromagnetic responses in time domain. Here we study time-filtering effects of such circuit-based metasurfaces illuminated by continuous sine waves. Moreover, we introduce extra circuit elements to these structures to enhance the time-domain control capability. These time-varying properties are expected to give us another degree of freedom to control electromagnetic waves and thus contribute to developing new kinds of electromagnetic applications and technologies, e.g. time-windowing wireless communications and waveform conversion. PMID:26564027

  8. Domain specific software design for decision aiding

    NASA Technical Reports Server (NTRS)

    Keller, Kirby; Stanley, Kevin

    1992-01-01

    McDonnell Aircraft Company (MCAIR) is involved in many large multi-discipline design and development efforts of tactical aircraft. These involve a number of design disciplines that must be coordinated to produce an integrated design and a successful product. Our interpretation of a domain specific software design (DSSD) is that of a representation or framework that is specialized to support a limited problem domain. A DSSD is an abstract software design that is shaped by the problem characteristics. This parallels the theme of object-oriented analysis and design of letting the problem model directly drive the design. The DSSD concept extends the notion of software reusability to include representations or frameworks. It supports the entire software life cycle and specifically leads to improved prototyping capability, supports system integration, and promotes reuse of software designs and supporting frameworks. The example presented in this paper is the task network architecture or design which was developed for the MCAIR Pilot's Associate program. The task network concept supported both module development and system integration within the domain of operator decision aiding. It is presented as an instance where a software design exhibited many of the attributes associated with DSSD concept.

  9. Birdsong dialect patterns explained using magnetic domains

    NASA Astrophysics Data System (ADS)

    Burridge, James; Kenney, Steven

    2016-06-01

    The songs and calls of many bird species, like human speech, form distinct regional dialects. We suggest that the process of dialect formation is analogous to the physical process of magnetic domain formation. We take the coastal breeding grounds of the Puget Sound white crowned sparrow as an example. Previous field studies suggest that birds of this species learn multiple songs early in life, and when establishing a territory for the first time, retain one of these dialects in order to match the majority of their neighbors. We introduce a simple lattice model of the process, showing that this matching behavior can produce single dialect domains provided the death rate of adult birds is sufficiently low. We relate death rate to thermodynamic temperature in magnetic materials, and calculate the critical death rate by analogy with the Ising model. Using parameters consistent with the known behavior of these birds we show that coastal dialect domain shapes may be explained by viewing them as low-temperature "stripe states."

  10. Domain theoretic structures in quantum information theory

    NASA Astrophysics Data System (ADS)

    Feng, Johnny

    2011-12-01

    In this thesis, we continue the study of domain theoretic structures in quantum information theory initiated by Keye Martin and Bob Coecke in 2002. The first part of the thesis is focused on exploring the domain theoretic properties of qubit channels. We discover that the Scott continuous qubit channels are exactly those that are unital or constant. We then prove that the unital qubit channels form a continuous dcpo, and identify various measurements on them. We show that Holevo capacity is a measurement on unital qubit channels, and discover the natural measurement in this setting. We find that qubit channels also form a continuous dcpo, but capacity fails to be a measurement. In the second part we focus on the study of exact dcpos, a domain theoretic structure, closely related to continuous dcpos, possessed by quantum states. Exact dcpos admit a topology, called the exact topology, and we show that the exact topology has an order theoretic characterization similar to the characterization of the Scott topology on continuous dcpos. We then explore the connection between exact and continuous dcpos; first, by identifying an important set of points, called the split points, that distinguishes between exact and continuous structures; second, by exploring a continuous completion of exact dcpos, and showing that we can recover the exact topology from the Scott topology of the completion.

  11. Energy of domain walls in ferrite films

    NASA Astrophysics Data System (ADS)

    Gomez, M. E.; Prieto, P.; Mendoza, A.; Guzman, O.

    2007-03-01

    MnZn Ferrite films were deposited by RF sputtering on (001) single crystal MgO substrates. AFM images show an increment in grain size with the film thickness. Grains with diameter between φ ˜ 70 and 700 nm have been observed. The coercive field Hc as a function of the grain size reaches a maximum value of about 80 Oe for φc˜ 300 nm. The existence of a multidomain structure associated with a critical grain size was identified by Magneto-optical Kerr effect technique (MOKE). The transition of the one-domain regime to the two-domain regime was observed at a critical grain size of Dc˜ 530 nm. This value agree with values predicted previously. The Jiles-Atherton model (JAM) was used to discuss the experimental hysteresis loops. The k pinning parameter obtained from JAM shows a maximum value of k/μo = 67 Am^2 for grains with Lc˜ 529 nm. The total energy per unit area E was correlated with k and D. We found a simple phenomenological relationship given by E α kD; where D is the magnetic domain width.

  12. Birdsong dialect patterns explained using magnetic domains.

    PubMed

    Burridge, James; Kenney, Steven

    2016-06-01

    The songs and calls of many bird species, like human speech, form distinct regional dialects. We suggest that the process of dialect formation is analogous to the physical process of magnetic domain formation. We take the coastal breeding grounds of the Puget Sound white crowned sparrow as an example. Previous field studies suggest that birds of this species learn multiple songs early in life, and when establishing a territory for the first time, retain one of these dialects in order to match the majority of their neighbors. We introduce a simple lattice model of the process, showing that this matching behavior can produce single dialect domains provided the death rate of adult birds is sufficiently low. We relate death rate to thermodynamic temperature in magnetic materials, and calculate the critical death rate by analogy with the Ising model. Using parameters consistent with the known behavior of these birds we show that coastal dialect domain shapes may be explained by viewing them as low-temperature "stripe states." PMID:27415293

  13. Evaluating, comparing, and interpreting protein domain hierarchies.

    PubMed

    Neuwald, Andrew F

    2014-04-01

    Arranging protein domain sequences hierarchically into evolutionarily divergent subgroups is important for investigating evolutionary history, for speeding up web-based similarity searches, for identifying sequence determinants of protein function, and for genome annotation. However, whether or not a particular hierarchy is optimal is often unclear, and independently constructed hierarchies for the same domain can often differ significantly. This article describes methods for statistically evaluating specific aspects of a hierarchy, for probing the criteria underlying its construction and for direct comparisons between hierarchies. Information theoretical notions are used to quantify the contributions of specific hierarchical features to the underlying statistical model. Such features include subhierarchies, sequence subgroups, individual sequences, and subgroup-associated signature patterns. Underlying properties are graphically displayed in plots of each specific feature's contributions, in heat maps of pattern residue conservation, in "contrast alignments," and through cross-mapping of subgroups between hierarchies. Together, these approaches provide a deeper understanding of protein domain functional divergence, reveal uncertainties caused by inconsistent patterns of sequence conservation, and help resolve conflicts between competing hierarchies.

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

    NASA Astrophysics Data System (ADS)

    Marrows, C. H.; Meier, G.

    2012-01-01

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

  15. Antiferromagnetic Domain Wall Motion Driven by Spin-Orbit Torques.

    PubMed

    Shiino, Takayuki; Oh, Se-Hyeok; Haney, Paul M; Lee, Seo-Won; Go, Gyungchoon; Park, Byong-Guk; Lee, Kyung-Jin

    2016-08-19

    We theoretically investigate the dynamics of antiferromagnetic domain walls driven by spin-orbit torques in antiferromagnet-heavy-metal bilayers. We show that spin-orbit torques drive antiferromagnetic domain walls much faster than ferromagnetic domain walls. As the domain wall velocity approaches the maximum spin-wave group velocity, the domain wall undergoes Lorentz contraction and emits spin waves in the terahertz frequency range. The interplay between spin-orbit torques and the relativistic dynamics of antiferromagnetic domain walls leads to the efficient manipulation of antiferromagnetic spin textures and paves the way for the generation of high frequency signals from antiferromagnets. PMID:27588878

  16. Anisotropic domain structure of KTiOPO4 crystals

    NASA Astrophysics Data System (ADS)

    Urenski, P.; Lesnykh, M.; Rosenwaks, Y.; Rosenman, G.; Molotskii, M.

    2001-08-01

    Highly anisotropic ferroelectric domain structure is observed in KTiOPO4 (KTP) crystals reversed by low electric field. The applied Miller-Weinreich model for sidewise motion of domain walls indicates that this anisotropy results from the peculiarities of KTP crystal lattice. The domain nuclei of dozen nanometer size, imaged by atomic force microscopy method, demonstrate regular hexagonal forms. The orientation of domain walls of the elementary nuclei coincides with the orientation of the facets of macroscopic KTP crystals. The observed strong domain elongation along one principal crystal axis allows us to improve tailoring of ferroelectric domain engineered structures for nonlinear optical converters.

  17. Antiferromagnetic Domain Wall Motion Driven by Spin-Orbit Torques

    NASA Astrophysics Data System (ADS)

    Shiino, Takayuki; Oh, Se-Hyeok; Haney, Paul M.; Lee, Seo-Won; Go, Gyungchoon; Park, Byong-Guk; Lee, Kyung-Jin

    2016-08-01

    We theoretically investigate the dynamics of antiferromagnetic domain walls driven by spin-orbit torques in antiferromagnet-heavy-metal bilayers. We show that spin-orbit torques drive antiferromagnetic domain walls much faster than ferromagnetic domain walls. As the domain wall velocity approaches the maximum spin-wave group velocity, the domain wall undergoes Lorentz contraction and emits spin waves in the terahertz frequency range. The interplay between spin-orbit torques and the relativistic dynamics of antiferromagnetic domain walls leads to the efficient manipulation of antiferromagnetic spin textures and paves the way for the generation of high frequency signals from antiferromagnets.

  18. Cache domains that are homologous to, but different from PAS domains comprise the largest superfamily of extracellular sensors in prokaryotes

    DOE PAGES

    Upadhyay, Amit A.; Fleetwood, Aaron D.; Adebali, Ogun; Finn, Robert D.; Zhulin, Igor B.; Schlessinger, Avner

    2016-04-06

    Cellular receptors usually contain a designated sensory domain that recognizes the signal. Per/Arnt/Sim (PAS) domains are ubiquitous sensors in thousands of species ranging from bacteria to humans. Although PAS domains were described as intracellular sensors, recent structural studies revealed PAS-like domains in extracytoplasmic regions in several transmembrane receptors. However, these structurally defined extracellular PAS-like domains do not match sequence-derived PAS domain models, and thus their distribution across the genomic landscape remains largely unknown. Here we show that structurally defined extracellular PAS-like domains belong to the Cache superfamily, which is homologous to, but distinct from the PAS superfamily. Our newly builtmore » computational models enabled identification of Cache domains in tens of thousands of signal transduction proteins including those from important pathogens and model organisms.Moreover, we show that Cache domains comprise the dominant mode of extracellular sensing in prokaryotes.« less

  19. Cache Domains That are Homologous to, but Different from PAS Domains Comprise the Largest Superfamily of Extracellular Sensors in Prokaryotes.

    PubMed

    Upadhyay, Amit A; Fleetwood, Aaron D; Adebali, Ogun; Finn, Robert D; Zhulin, Igor B

    2016-04-01

    Cellular receptors usually contain a designated sensory domain that recognizes the signal. Per/Arnt/Sim (PAS) domains are ubiquitous sensors in thousands of species ranging from bacteria to humans. Although PAS domains were described as intracellular sensors, recent structural studies revealed PAS-like domains in extracytoplasmic regions in several transmembrane receptors. However, these structurally defined extracellular PAS-like domains do not match sequence-derived PAS domain models, and thus their distribution across the genomic landscape remains largely unknown. Here we show that structurally defined extracellular PAS-like domains belong to the Cache superfamily, which is homologous to, but distinct from the PAS superfamily. Our newly built computational models enabled identification of Cache domains in tens of thousands of signal transduction proteins including those from important pathogens and model organisms. Furthermore, we show that Cache domains comprise the dominant mode of extracellular sensing in prokaryotes.

  20. Cache Domains That are Homologous to, but Different from PAS Domains Comprise the Largest Superfamily of Extracellular Sensors in Prokaryotes.

    PubMed

    Upadhyay, Amit A; Fleetwood, Aaron D; Adebali, Ogun; Finn, Robert D; Zhulin, Igor B

    2016-04-01

    Cellular receptors usually contain a designated sensory domain that recognizes the signal. Per/Arnt/Sim (PAS) domains are ubiquitous sensors in thousands of species ranging from bacteria to humans. Although PAS domains were described as intracellular sensors, recent structural studies revealed PAS-like domains in extracytoplasmic regions in several transmembrane receptors. However, these structurally defined extracellular PAS-like domains do not match sequence-derived PAS domain models, and thus their distribution across the genomic landscape remains largely unknown. Here we show that structurally defined extracellular PAS-like domains belong to the Cache superfamily, which is homologous to, but distinct from the PAS superfamily. Our newly built computational models enabled identification of Cache domains in tens of thousands of signal transduction proteins including those from important pathogens and model organisms. Furthermore, we show that Cache domains comprise the dominant mode of extracellular sensing in prokaryotes. PMID:27049771

  1. Cache Domains That are Homologous to, but Different from PAS Domains Comprise the Largest Superfamily of Extracellular Sensors in Prokaryotes

    PubMed Central

    Upadhyay, Amit A.; Fleetwood, Aaron D.; Adebali, Ogun; Finn, Robert D.; Zhulin, Igor B.

    2016-01-01

    Cellular receptors usually contain a designated sensory domain that recognizes the signal. Per/Arnt/Sim (PAS) domains are ubiquitous sensors in thousands of species ranging from bacteria to humans. Although PAS domains were described as intracellular sensors, recent structural studies revealed PAS-like domains in extracytoplasmic regions in several transmembrane receptors. However, these structurally defined extracellular PAS-like domains do not match sequence-derived PAS domain models, and thus their distribution across the genomic landscape remains largely unknown. Here we show that structurally defined extracellular PAS-like domains belong to the Cache superfamily, which is homologous to, but distinct from the PAS superfamily. Our newly built computational models enabled identification of Cache domains in tens of thousands of signal transduction proteins including those from important pathogens and model organisms. Furthermore, we show that Cache domains comprise the dominant mode of extracellular sensing in prokaryotes. PMID:27049771

  2. Thermomagnetic Stability in Pseudo Single Domain Grains

    NASA Astrophysics Data System (ADS)

    Nagy, Lesleis; Williams, Wyn; Muxworthy, Adrian; Fabian, Karl; Conbhuí, Pádraig Ó.

    2016-04-01

    The reliability of paleomagnetic remanences are well understood for fine grains of magnetite that are single-domain (SD, uniformly magnetized). In particular Néel's theory [1] outlined the thermal energies required to block and unblock magnetic remanences. This lead to determination of thermal stability for magnetization in fine grains as outlined in Pullaiah et. al. [2] and a comprehensive understanding of SD paleomagnetic recordings. It has been known for some time that single domain magnetite is possible only in the grain size range 30 - 80nm, which may only account for a small fraction of the grain size distribution in any rock sample. Indeed rocks are often dominated by grains in the pseudo single domain (PSD) size range, at approximately 80 - 1000nm. Toward the top end of this range multi-domain features begin to dominate. In order to determine thermomagnetic stability in PSD grains we need to identify the energy barriers between all possible pairs of local energy minima (LEM) domain states as a function of both temperature and grain size. We have attempted to do this using the nudged elastic band (NEB) method [3] which searches for minimum energy paths between any given pair of LEM states. Using this technique we have determined, for the first time, complete thermomagnetic stability curves for PSD magnetite. The work presented is at a preliminary stage. However it can be shown that PSD grains of magnetite with simple geometries (e.g. cubes or cuboctahedra) have very few low energy transition paths and the stability is likely to be similar to that observed for SD grains (as expected form experimental observations). The results will provide a basis for a much more rigorous understanding of the fidelity of paleomagnetic signals in assemblages of PSD grains and their ability to retain ancient recordings of the geomagnetic field. References: [1] Néel, Louis. "Théorie du traînage magnétique des ferromagnétiques en grains fins avec applications aux terres

  3. Flowing on Riemannian manifold: domain adaptation by shifting covariance.

    PubMed

    Cui, Zhen; Li, Wen; Xu, Dong; Shan, Shiguang; Chen, Xilin; Li, Xuelong

    2014-12-01

    Domain adaptation has shown promising results in computer vision applications. In this paper, we propose a new unsupervised domain adaptation method called domain adaptation by shifting covariance (DASC) for object recognition without requiring any labeled samples from the target domain. By characterizing samples from each domain as one covariance matrix, the source and target domain are represented into two distinct points residing on a Riemannian manifold. Along the geodesic constructed from the two points, we then interpolate some intermediate points (i.e., covariance matrices), which are used to bridge the two domains. By utilizing the principal components of each covariance matrix, samples from each domain are further projected into intermediate feature spaces, which finally leads to domain-invariant features after the concatenation of these features from intermediate points. In the multiple source domain adaptation task, we also need to effectively integrate different types of features between each pair of source and target domains. We additionally propose an SVM based method to simultaneously learn the optimal target classifier as well as the optimal weights for different source domains. Extensive experiments demonstrate the effectiveness of our method for both single source and multiple source domain adaptation tasks.

  4. DIMA 2.0--predicted and known domain interactions.

    PubMed

    Pagel, Philipp; Oesterheld, Matthias; Tovstukhina, Oksana; Strack, Norman; Stümpflen, Volker; Frishman, Dmitrij

    2008-01-01

    DIMA-the domain interaction map has evolved from a simple web server for domain phylogenetic profiling into an integrative prediction resource combining both experimental data on domain-domain interactions and predictions from two different algorithms. With this update, DIMA obtains greatly improved coverage at the level of genomes and domains as well as with respect to available prediction approaches. The domain phylogenetic profiling method now uses SIMAP as its backend for exhaustive domain hit coverage: 7038 Pfam domains were profiled over 460 completely sequenced genomes. Domain pair exclusion predictions were produced from 83 969 distinct protein-protein interactions obtained from IntAct resulting in 21 513 domain pairs with significant domain pair exclusion algorithm scores. Additional predictions applying the same algorithm to predicted protein interactions from STRING yielded 2378 high-confidence pairs. Experimental data comes from iPfam (3074) and 3did (3034 pairs), two databases identifying domain contacts in solved protein structures. Taken together, these two resources yielded 3653 distinct interacting domain pairs. DIMA is available at http://mips.gsf.de/genre/proj/dima.

  5. Characterisation of Schizosaccharomyces pombe α-actinin.

    PubMed

    Addario, Barbara; Sandblad, Linda; Persson, Karina; Backman, Lars

    2016-01-01

    The actin cytoskeleton plays a fundamental role in eukaryotic cells. Its reorganization is regulated by a plethora of actin-modulating proteins, such as a-actinin. In higher organisms, α-actinin is characterized by the presence of three distinct structural domains: an N-terminal actin-binding domain and a C-terminal region with EF-hand motif separated by a central rod domain with four spectrin repeats. Sequence analysis has revealed that the central rod domain of α-actinin from the fission yeast Schizosaccharomyces pombe consists of only two spectrin repeats. To obtain a firmer understanding of the structure and function of this unconventional α-actinin, we have cloned and characterized each structural domain. Our results show that this a-actinin isoform is capable of forming dimers and that the rod domain is required for this. However, its actin-binding and cross-linking activity appears less efficient compared to conventional α-actinins. The solved crystal structure of the actin-binding domain indicates that the closed state is stabilised by hydrogen bonds and a salt bridge not present in other α-actinins, which may reduce the affinity for actin.

  6. Characterisation of Schizosaccharomyces pombe α-actinin

    PubMed Central

    Addario, Barbara; Sandblad, Linda; Persson, Karina

    2016-01-01

    The actin cytoskeleton plays a fundamental role in eukaryotic cells. Its reorganization is regulated by a plethora of actin-modulating proteins, such as a-actinin. In higher organisms, α-actinin is characterized by the presence of three distinct structural domains: an N-terminal actin-binding domain and a C-terminal region with EF-hand motif separated by a central rod domain with four spectrin repeats. Sequence analysis has revealed that the central rod domain of α-actinin from the fission yeast Schizosaccharomyces pombe consists of only two spectrin repeats. To obtain a firmer understanding of the structure and function of this unconventional α-actinin, we have cloned and characterized each structural domain. Our results show that this a-actinin isoform is capable of forming dimers and that the rod domain is required for this. However, its actin-binding and cross-linking activity appears less efficient compared to conventional α-actinins. The solved crystal structure of the actin-binding domain indicates that the closed state is stabilised by hydrogen bonds and a salt bridge not present in other α-actinins, which may reduce the affinity for actin. PMID:27069798

  7. Correlation between spin structure oscillations and domain wall velocities

    PubMed Central

    Bisig, André; Stärk, Martin; Mawass, Mohamad-Assaad; Moutafis, Christoforos; Rhensius, Jan; Heidler, Jakoba; Büttner, Felix; Noske, Matthias; Weigand, Markus; Eisebitt, Stefan; Tyliszczak, Tolek; Van Waeyenberge, Bartel; Stoll, Hermann; Schütz, Gisela; Kläui, Mathias

    2013-01-01

    Magnetic sensing and logic devices based on the motion of magnetic domain walls rely on the precise and deterministic control of the position and the velocity of individual magnetic domain walls in curved nanowires. Varying domain wall velocities have been predicted to result from intrinsic effects such as oscillating domain wall spin structure transformations and extrinsic pinning due to imperfections. Here we use direct dynamic imaging of the nanoscale spin structure that allows us for the first time to directly check these predictions. We find a new regime of oscillating domain wall motion even below the Walker breakdown correlated with periodic spin structure changes. We show that the extrinsic pinning from imperfections in the nanowire only affects slow domain walls and we identify the magnetostatic energy, which scales with the domain wall velocity, as the energy reservoir for the domain wall to overcome the local pinning potential landscape. PMID:23978905

  8. Generating target system specifications from a domain model using CLIPS

    NASA Technical Reports Server (NTRS)

    Sugumaran, Vijayan; Gomaa, Hassan; Kerschberg, Larry

    1991-01-01

    The quest for reuse in software engineering is still being pursued and researchers are actively investigating the domain modeling approach to software construction. There are several domain modeling efforts reported in the literature and they all agree that the components that are generated from domain modeling are more conducive to reuse. Once a domain model is created, several target systems can be generated by tailoring the domain model or by evolving the domain model and then tailoring it according to the specified requirements. This paper presents the Evolutionary Domain Life Cycle (EDLC) paradigm in which a domain model is created using multiple views, namely, aggregation hierarchy, generalization/specialization hierarchies, object communication diagrams and state transition diagrams. The architecture of the Knowledge Based Requirements Elicitation Tool (KBRET) which is used to generate target system specifications is also presented. The preliminary version of KBRET is implemented in the C Language Integrated Production System (CLIPS).

  9. Domain structure of black hole space-times

    SciTech Connect

    Harmark, Troels

    2009-07-15

    We introduce the domain structure for stationary black hole space-times. The domain structure lives on the submanifold of fixed points of the Killing vector fields. Depending on which Killing vector field has fixed points the submanifold is naturally divided into domains. The domain structure provides invariants of the space-time, both topological and continuous. It is defined for any space-time dimension and any number of Killing vector fields. We examine the domain structure for asymptotically flat space-times and find a canonical form for the metric of such space-times. The domain structure generalizes the rod structure introduced for space-times with D-2 commuting Killing vector fields. We analyze in detail the domain structure for Minkowski space, the Schwarzschild-Tangherlini black hole and the Myers-Perry black hole in six and seven dimensions. Finally, we consider the possible domain structures for asymptotically flat black holes in six and seven dimensio0008.

  10. Generalization Bounds Derived IPM-Based Regularization for Domain Adaptation.

    PubMed

    Meng, Juan; Hu, Guyu; Li, Dong; Zhang, Yanyan; Pan, Zhisong

    2016-01-01

    Domain adaptation has received much attention as a major form of transfer learning. One issue that should be considered in domain adaptation is the gap between source domain and target domain. In order to improve the generalization ability of domain adaption methods, we proposed a framework for domain adaptation combining source and target data, with a new regularizer which takes generalization bounds into account. This regularization term considers integral probability metric (IPM) as the distance between the source domain and the target domain and thus can bound up the testing error of an existing predictor from the formula. Since the computation of IPM only involves two distributions, this generalization term is independent with specific classifiers. With popular learning models, the empirical risk minimization is expressed as a general convex optimization problem and thus can be solved effectively by existing tools. Empirical studies on synthetic data for regression and real-world data for classification show the effectiveness of this method.

  11. Periodic magnetic domains in single-crystalline cobalt filament arrays

    NASA Astrophysics Data System (ADS)

    Chen, Fei; Wang, Fan; Jia, Fei; Li, Jingning; Liu, Kai; Huang, Sunxiang; Luan, Zhongzhi; Wu, Di; Chen, Yanbin; Zhu, Jianmin; Peng, Ru-Wen; Wang, Mu

    2016-02-01

    Magnetic structures with controlled domain wall pattern may be applied as potential building blocks for three-dimensional magnetic memory and logic devices. Using a unique electrochemical self-assembly method, we achieve regular single-crystalline cobalt filament arrays with specific geometric profile and crystallographic orientation, and the magnetic domain configuration can be conveniently tailored. We report the transition of periodic antiparallel magnetic domains to compressed vortex magnetic domains depending on the ratio of height to width of the wires. A "phase diagram" is obtained to describe the dependence of the type of magnetic domain and the geometrical profiles of the wires. Magnetoresistance of the filaments demonstrates that the contribution of a series of 180∘ domain walls is over 0.15 % of the zero-field resistance ρ (H =0 ) . These self-assembled magnetic nanofilaments, with controlled periodic domain patterns, offer an interesting platform to explore domain-wall-based memory and logic devices.

  12. Examining thermal transport through a frequency-domain representation of time-domain thermoreflectance data.

    PubMed

    Collins, Kimberlee C; Maznev, Alexei A; Cuffe, John; Nelson, Keith A; Chen, Gang

    2014-12-01

    Laser-based time-domain thermoreflectance (TDTR) and frequency-domain thermoreflectance (FDTR) techniques are widely used for investigating thermal transport at micro- and nano-scales. We demonstrate that data obtained in TDTR measurements can be represented in a frequency-domain form equivalent to FDTR, i.e., in the form of a surface temperature amplitude and phase response to time-harmonic heating. Such a representation is made possible by using a large TDTR delay time window covering the entire pulse repetition interval. We demonstrate the extraction of frequency-domain data up to 1 GHz from TDTR measurements on a sapphire sample coated with a thin layer of aluminum, and show that the frequency dependencies of both the amplitude and phase responses agree well with theory. The proposed method not only allows a direct comparison of TDTR and FDTR data, but also enables measurements at high frequencies currently not accessible to FDTR. The frequency-domain representation helps uncover aspects of the measurement physics which remain obscured in a traditional TDTR measurement, such as the importance of modeling the details of the heat transport in the metal transducer film for analyzing high frequency responses.

  13. Examining thermal transport through a frequency-domain representation of time-domain thermoreflectance data

    NASA Astrophysics Data System (ADS)

    Collins, Kimberlee C.; Maznev, Alexei A.; Cuffe, John; Nelson, Keith A.; Chen, Gang

    2014-12-01

    Laser-based time-domain thermoreflectance (TDTR) and frequency-domain thermoreflectance (FDTR) techniques are widely used for investigating thermal transport at micro- and nano-scales. We demonstrate that data obtained in TDTR measurements can be represented in a frequency-domain form equivalent to FDTR, i.e., in the form of a surface temperature amplitude and phase response to time-harmonic heating. Such a representation is made possible by using a large TDTR delay time window covering the entire pulse repetition interval. We demonstrate the extraction of frequency-domain data up to 1 GHz from TDTR measurements on a sapphire sample coated with a thin layer of aluminum, and show that the frequency dependencies of both the amplitude and phase responses agree well with theory. The proposed method not only allows a direct comparison of TDTR and FDTR data, but also enables measurements at high frequencies currently not accessible to FDTR. The frequency-domain representation helps uncover aspects of the measurement physics which remain obscured in a traditional TDTR measurement, such as the importance of modeling the details of the heat transport in the metal transducer film for analyzing high frequency responses.

  14. A bacterial collagen-binding domain with novel calcium-binding motif controls domain orientation

    PubMed Central

    Wilson, Jeffrey J.; Matsushita, Osamu; Okabe, Akinobu; Sakon, Joshua

    2003-01-01

    The crystal structure of a collagen-binding domain (CBD) with an N-terminal domain linker from Clostridium histolyticum class I collagenase was determined at 1.00 Å resolution in the absence of calcium (1NQJ) and at 1.65 Å resolution in the presence of calcium (1NQD). The mature enzyme is composed of four domains: a metalloprotease domain, a spacing domain and two CBDs. A 12-residue-long linker is found at the N-terminus of each CBD. In the absence of calcium, the CBD reveals a β-sheet sandwich fold with the linker adopting an α-helix. The addition of calcium unwinds the linker and anchors it to the distal side of the sandwich as a new β-strand. The conformational change of the linker upon calcium binding is confirmed by changes in the Stokes and hydrodynamic radii as measured by size exclusion chromatography and by dynamic light scattering with and without calcium. Furthermore, extensive mutagenesis of conserved surface residues and collagen-binding studies allow us to identify the collagen-binding surface of the protein and propose likely collagen–protein binding models. PMID:12682007

  15. Prediction of Domain Behavior through Dynamic Well-Being Domain Model Analysis

    PubMed Central

    Bosems, Steven; van Sinderen, Marten

    2015-01-01

    As the concept of context-awareness is becoming more popular the demand for improved quality of context-aware systems increases too. Due to the inherent challenges posed by context-awareness, it is harder to predict what the behavior of the systems and their context will be once provided to the end-user than is the case for non-context-aware systems. A domain where such upfront knowledge is highly important is that of well-being. In this paper, we introduce a method to model the well-being domain and to predict the effects the system will have on its context when implemented. This analysis can be performed at design time. Using these predictions, the design can be fine-tuned to increase the chance that systems will have the desired effect. The method has been tested using three existing well-being applications. For these applications, domain models were created in the Dynamic Well-being Domain Model language. This language allows for causal reasoning over the application domain. The models created were used to perform the analysis and behavior prediction. The analysis results were compared to existing application end-user evaluation studies. Results showed that our analysis could accurately predict success and possible problems in the focus of the systems, although certain limitation regarding the predictions should be kept into consideration. PMID:26351660

  16. The evolutionary analysis reveals domain fusion of proteins with Frizzled-like CRD domain.

    PubMed

    Yan, Jun; Jia, Haibo; Ma, Zhaowu; Ye, Huashan; Zhou, Mi; Su, Li; Liu, Jianfeng; Guo, An-Yuan

    2014-01-01

    Frizzleds (FZDs) are transmembrane receptors in the Wnt signaling pathway and they play pivotal roles in developments. The Frizzled-like extracellular Cysteine-rich domain (Fz-CRD) has been identified in FZDs and other proteins. The origin and evolution of these proteins with Fz-CRD is the main interest of this study. We found that the Fz-CRD exists in FZD, SFRP, RTK, MFRP, CPZ, CORIN, COL18A1 and other proteins. Our systematic analysis revealed that the Fz-CRD domain might have originated in protists and then fused with the Frizzled-like seven-transmembrane domain (7TM) to form the FZD receptors, which duplicated and diversified into about 11 members in Vertebrates. The SFRPs and RTKs with the Fz-CRD were found in sponge and expanded in Vertebrates. Other proteins with Fz-CRD may have emerged during Vertebrate evolution through domain fusion. Moreover, we found a glycosylation site and several conserved motifs in FZDs, which may be related to Wnt interaction. Based on these results, we proposed a model showing that the domain fusion and expansion of Fz-CRD genes occurred in Metazoa and Vertebrates. Our study may help to pave the way for further research on the conservation and diversification of Wnt signaling functions during evolution.

  17. Prediction of VH-VL domain orientation for antibody variable domain modeling.

    PubMed

    Bujotzek, Alexander; Dunbar, James; Lipsmeier, Florian; Schäfer, Wolfgang; Antes, Iris; Deane, Charlotte M; Georges, Guy

    2015-04-01

    The antigen-binding site of antibodies forms at the interface of their two variable domains, VH and VL, making VH-VL domain orientation a factor that codetermines antibody specificity and affinity. Preserving VH-VL domain orientation in the process of antibody engineering is important in order to retain the original antibody properties, and predicting the correct VH-VL orientation has also been recognized as an important factor in antibody homology modeling. In this article, we present a fast sequence-based predictor that predicts VH-VL domain orientation with Q(2) values ranging from 0.54 to 0.73 on the evaluation set. We describe VH-VL orientation in terms of the six absolute ABangle parameters that have recently been proposed as a means to separate the different degrees of freedom of VH-VL domain orientation. In order to assess the impact of adjusting VH-VL orientation according to our predictions, we use the set of antibody structures of the recently published Antibody Modeling Assessment (AMA) II study. In comparison to the original AMAII homology models, we find an improvement in the accuracy of VH-VL orientation modeling, which also translates into an improvement in the average root-mean-square deviation with regard to the crystal structures.

  18. Apoplastic domains and sub-domains in the shoots of etiolated corn seedlings

    NASA Technical Reports Server (NTRS)

    Epel, B. L.; Bandurski, R. S.

    1990-01-01

    Light Green, an apoplastic probe, was applied to the cut mesocotyl base or to the cut coleoptile apex of etiolated seedlings of Zea mays L. cv. Silver Queen. Probe transport was measured and its tissue distribution determined. In the mesocotyl, there is an apoplastic barrier between cortex and stele. This barrier creates two apoplastic domains which are non-communicating. A kinetic barrier exists between the apoplast of the mesocotyl stele and that of the coleoptile. This kinetic barrier is not absolute and there is limited communication between the apoplasts of the two regions. This kinetic barrier effectively creates two sub-domains. In the coleoptile, there is communication between the apoplast of the vascular strands and that of the surrounding cortical tissue. No apoplastic communication was observed between the coleoptile cortex and the mesocotyl cortex. Thus, the apoplastic space of the coleoptile cortex is a sub-domain of the integrated coleoptile domain and is separate from that of the apoplastic domain of the mesocotyl cortex.

  19. Entropy production by domain wall decay in the NMSSM

    NASA Astrophysics Data System (ADS)

    Hattori, Hironori; Kobayashi, Tatsuo; Omoto, Naoya; Seto, Osamu

    2015-11-01

    We consider domain walls in the Z3 symmetric next-to-minimal supersymmetric standard model. The spontaneous Z3 discrete symmetry breaking produces domain walls, and the stable domain walls are problematic. Thus, we assume the Z3 symmetry is slightly but explicitly broken and the domain walls decay. Such a decay causes a large late-time entropy production. We study its cosmological implications on unwanted relics such as the moduli, gravitino, lightest superparticle, and axion.

  20. The Allosteric Mechanism Induced by Protein Kinase A (PKA) Phosphorylation of Dematin (Band 4.9)*

    PubMed Central

    Chen, Lin; Brown, Jeffrey W.; Mok, Yee-Foong; Hatters, Danny M.; McKnight, C. James

    2013-01-01

    Dematin (band 4.9) is an F-actin binding and bundling protein best known for its role within red blood cells, where it both stabilizes as well as attaches the spectrin/actin cytoskeleton to the erythrocytic membrane. Here, we investigate the structural consequences of phosphorylating serine 381, a covalent modification that turns off F-actin bundling activity. In contrast to the canonical doctrine, in which phosphorylation of an intrinsically disordered region/protein confers affinity for another domain/protein, we found the converse to be true of dematin: phosphorylation of the well folded C-terminal villin-type headpiece confers affinity for its intrinsically disordered N-terminal core domain. We employed analytical ultracentrifugation to demonstrate that dematin is monomeric, in contrast to the prevailing view that it is trimeric. Next, using a series of truncation mutants, we verified that dematin has two F-actin binding sites, one in the core domain and the other in the headpiece domain. Although the phosphorylation-mimicking mutant, S381E, was incapable of bundling microfilaments, it retains the ability to bind F-actin. We found that a phosphorylation-mimicking mutant, S381E, eliminated the ability to bundle, but not bind F-actin filaments. Lastly, we show that the S381E point mutant caused the headpiece domain to associate with the core domain, leading us to the mechanism for cAMP-dependent kinase control of dematin's F-actin bundling activity: when unphosphorylated, dematin's two F-actin binding domains move independent of one another permitting them to bind different F-actin filaments. Phosphorylation causes these two domains to associate, forming a compact structure, and sterically eliminating one of these F-actin binding sites. PMID:23355471

  1. Spatial-domain optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Langevin, L.; Gay, D.; Piché, M.

    2008-06-01

    Optical coherence tomography (OCT) is a non-invasive imaging technique invented in 1991 and allowing the observation of biological tissues with millimeter depth of penetration and a few micrometer resolution. In the standard time-domain OCT setup (TD-OCT), a broadband light source is used with a Michelson interferometer where one of the mirrors is replaced by the sample (which is mechanically moved transversally during data acquisition) while the other is axially vibrating. By analyzing the temporal signal at the exit of the interferometer, a high resolution tomographic cut of the sample can be obtained. A number of new OCT setups have been proposed since 1991 in order to improve the data acquisition speed. In particular, Fourier-domain OCT (FD-OCT) has allowed in vivo observation of samples by eliminating the necessity of the axial motion of the reference mirror in the setup. We propose in this paper new OCT setups having the same potential without requiring numerical treatment of the signal (as it is the case in FD-OCT). Because those setups are such that the axial information of the sample becomes linearly distributed at different points of space in an interference pattern, we call them spatial-domain OCT setups (SD-OCT). SD-OCT setups use a tilted mirror in a Michelson interferometer to produce an interference pattern which is imaged on a CCD detector. The pattern contains all the information on the sample and is obtained without mechanical motion or numerical treatment of the recorded signal. In order to validate the proposed scheme, prototypes of the setups have been made in the laboratories of COPL at Laval University; biological samples such as onion peels and phloem of trees have been tested in order to produce their tomographic images. Comparisons of some of our results with those from a commercial setup with the same samples had notably confirmed the capacity of ours prototypes to effectively image biological samples.

  2. Credentialing Data Scientists: A Domain Repository Perspective

    NASA Astrophysics Data System (ADS)

    Lehnert, K. A.; Furukawa, H.

    2015-12-01

    A career in data science can have many paths: data curation, data analysis, metadata modeling - all of these in different commercial or scientific applications. Can a certification as 'data scientist' provide the guarantee that an applicant or candidate for a data science position has just the right skills? How valuable is a 'generic' certification as data scientist for an employer looking to fill a data science position? Credentials that are more specific and discipline-oriented may be more valuable to both the employer and the job candidate. One employment sector for data scientists are the data repositories that provide discipline-specific data services for science communities. Data science positions within domain repositories include a wide range of responsibilities in support of the full data life cycle - from data preservation and curation to development of data models, ontologies, and user interfaces, to development of data analysis and visualization tools to community education and outreach, and require a substantial degree of discipline-specific knowledge of scientific data acquisition and analysis workflows, data quality measures, and data cultures. Can there be certification programs for domain-specific data scientists that help build the urgently needed workforce for the repositories? The American Geophysical Union has recently started an initiative to develop a program for data science continuing education and data science professional certification for the Earth and space sciences. An Editorial Board has been charged to identify and develop curricula and content for these programs and to provide input and feedback in the implementation of the program. This presentation will report on the progress of this initiative and evaluate its utility for the needs of domain repositories in the Earth and space sciences.

  3. Stochastic finite-difference time-domain

    NASA Astrophysics Data System (ADS)

    Smith, Steven Michael

    2011-12-01

    This dissertation presents the derivation of an approximate method to determine the mean and the variance of electro-magnetic fields in the body using the Finite-Difference Time-Domain (FDTD) method. Unlike Monte Carlo analysis, which requires repeated FDTD simulations, this method directly computes the variance of the fields at every point in space at every sample of time in the simulation. This Stochastic FDTD simulation (S-FDTD) has at its root a new wave called the Variance wave, which is computed in the time domain along with the mean properties of the model space in the FDTD simulation. The Variance wave depends on the electro-magnetic fields, the reflections and transmission though the different dielectrics, and the variances of the electrical properties of the surrounding materials. Like the electro-magnetic fields, the Variance wave begins at zero (there is no variance before the source is turned on) and is computed in the time domain until all fields reach steady state. This process is performed in a fraction of the time of a Monte Carlo simulation and yields the first two statistical parameters (mean and variance). The mean of the field is computed using the traditional FDTD equations. Variance is computed by approximating the correlation coefficients between the constituitive properties and the use of the S-FDTD equations. The impetus for this work was the simulation time it takes to perform 3D Specific Absorption Rate (SAR) FDTD analysis of the human head model for cell phone power absorption in the human head due to the proximity of a cell phone being used. In many instances, Monte Carlo analysis is not performed due to the lengthy simulation times required. With the development of S-FDTD, these statistical analyses could be performed providing valuable statistical information with this information being provided in a small fraction of the time it would take to perform a Monte Carlo analysis.

  4. Boosting domain wall propagation by notches

    NASA Astrophysics Data System (ADS)

    Yuan, H. Y.; Wang, X. R.

    2015-08-01

    We report a counterintuitive finding that notches in an otherwise homogeneous magnetic nanowire can boost current-induced domain wall (DW) propagation. DW motion in notch-modulated wires can be classified into three phases: (1) A DW is pinned around a notch when the current density is below the depinning current density. (2) DW propagation velocity is boosted by notches above the depinning current density and when nonadiabatic spin-transfer torque strength β is smaller than the Gilbert damping constant α . The boost can be multifold. (3) DW propagation velocity is hindered when β >α . The results are explained by using the Thiele equation.

  5. FIND: Fluorescence Imaging in the Nuclear Domain

    SciTech Connect

    Barty, C J

    2005-02-14

    This document examines the potential use of Thomson-Radiated Extreme X-ray (T-REX) sources for Fluorescence Imaging in the Nuclear Domain (FIND) of special nuclear materials. A back-of-the-envelope, relative comparison of T-REX sources vs. Bremsstrahlung sources for this application is presented. It is estimated that use of T-REX for FIND could be as much as 5 x 10{sup 12} more effective than the use of anode based sources. Furthermore it is estimated that illumination of samples of dimension 1 cm on a side could produce up to {approx}10{sup 9} detectable photons per second.

  6. Applications of Terahertz Time-Domain Reflectometry

    NASA Astrophysics Data System (ADS)

    Kitahara, Hideaki; Takano, Keisuke; Ikeda, Takeshi; Tani, Masahiko; Hangyo, Masanori

    A reflection-type terahertz (THz) time-domain spectroscopy (TDS) is applied to non-contact and non-destructive diagnosis of the surface and inner-structure of test samples. Raster scan imaging and THz optical coherence tomography (THz-OCT) are demonstrated for a bank bill, a high voltage cable and an indented impression on a memo-pad paper. The watermark of the bank bill, the indented impression, and a flaw in the cable are detected successfully. These results indicate that THz imaging is potentially useful for the analysis of surfaces and inner-structures of products made with various materials.

  7. Dental optical coherence domain reflectometry explorer

    DOEpatents

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

    2001-01-01

    A hand-held, fiber optic based dental device with optical coherence domain reflectometry (OCDR) sensing capabilities provides a profile of optical scattering as a function of depth in the tissue at the point where the tip of the dental explorer touches the tissue. This system provides information on the internal structure of the dental tissue, which is then used to detect caries and periodontal disease. A series of profiles of optical scattering or tissue microstructure are generated by moving the explorer across the tooth or other tissue. The profiles are combined to form a cross-sectional, or optical coherence tomography (OCT), image.

  8. Time-domain multiple-quantum NMR

    SciTech Connect

    Weitekamp, D.P.

    1982-11-01

    The development of time-domain multiple-quantum nuclear magnetic resonance is reviewed through mid 1982 and some prospects for future development are indicated. Particular attention is given to the problem of obtaining resolved, interpretable, many-quantum spectra for anisotropic magnetically isolated systems of coupled spins. New results are presented on a number of topics including the optimization of multiple-quantum-line intensities, analysis of noise in two-dimensional spectroscopy, and the use of order-selective excitation for cross polarization between nuclear-spin species.

  9. Magnetic domain wall motion by spin transfer

    NASA Astrophysics Data System (ADS)

    Grollier, Julie; Chanthbouala, A.; Matsumoto, R.; Anane, A.; Cros, V.; Nguyen van Dau, F.; Fert, Albert

    2011-04-01

    The discovery that a spin polarized current can exert a large torque on a ferromagnet through a transfusion of spin angular momentum, offers a new way to control a magnetization by simple current injection, without the help of an applied external field. Spin transfer can be used to induce magnetization reversals and oscillations, or to control the position of a magnetic domain wall. In this review, we focus on this last mechanism, which is today the subject of an extensive research, both because the microscopic details for its origin are still debated, but also because promising applications are at stake for non-volatile magnetic memories.

  10. Constricted nanowire with stabilized magnetic domain wall

    NASA Astrophysics Data System (ADS)

    Sbiaa, R.; Al Bahri, M.

    2016-08-01

    Domain wall (DW)-based magnetic memory offers the possibility for increasing the storage capacity. However, stability of DW remains the major drawback of this scheme. In this letter, we propose a stepped nanowire for pinning DW in a desirable position. From micromagnetic simulation, the proposed design applied to in-plane magnetic anisotropy materials shows that by adjusting the nanowire step size and its width it is possible to stabilize DW for a desirable current density range. In contrast, only a movement of DW could be seen for conventional nanowire. An extension to a multi-stepped nanowire could be used for multi-bit per cell magnetic memory.

  11. Lattice gas simulations of replicating domains

    SciTech Connect

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

    1993-12-31

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

  12. Cross-domain active learning for video concept detection

    NASA Astrophysics Data System (ADS)

    Li, Huan; Li, Chao; Shi, Yuan; Xiong, Zhang; Hauptmann, Alexander G.

    2011-08-01

    As video data from a variety of different domains (e.g., news, documentaries, entertainment) have distinctive data distributions, cross-domain video concept detection becomes an important task, in which one can reuse the labeled data of one domain to benefit the learning task in another domain with insufficient labeled data. In this paper, we approach this problem by proposing a cross-domain active learning method which iteratively queries labels of the most informative samples in the target domain. Traditional active learning assumes that the training (source domain) and test data (target domain) are from the same distribution. However, it may fail when the two domains have different distributions because querying informative samples according to a base learner that initially learned from source domain may no longer be helpful for the target domain. In our paper, we use the Gaussian random field model as the base learner which has the advantage of exploring the distributions in both domains, and adopt uncertainty sampling as the query strategy. Additionally, we present an instance weighting trick to accelerate the adaptability of the base learner, and develop an efficient model updating method which can significantly speed up the active learning process. Experimental results on TRECVID collections highlight the effectiveness.

  13. Domain Specificity between Peer Support and Self-Concept

    ERIC Educational Resources Information Center

    Leung, Kim Chau; Marsh, Herbert W.; Craven, Rhonda G.; Yeung, Alexander S.; Abduljabbar, Adel S.

    2013-01-01

    Peer support interventions have mostly neglected the domain specificity of intervention effects. In two studies, the present investigation examined the domain specificity of peer support interventions targeting specific domains of self-concept. In Study 1, participants ("n" = 50) who had received an academically oriented peer support intervention…

  14. Changing Your Domain Name in 25 Nail-Biting Steps

    ERIC Educational Resources Information Center

    Hassler, Carol

    2012-01-01

    When staff at the Wisconsin State Law Library began compiling a wish list for a new website, the topic of a new domain name came up almost immediately. Their old website was located at http://wsll.state.wi.us. Spelling that relatively complex domain over the phone day after day provided the impetus to explore other options. Whatever domain name…

  15. Conception of Learning Outcomes in the Bloom's Taxonomy Affective Domain

    ERIC Educational Resources Information Center

    Savickiene, Izabela

    2010-01-01

    The article raises a problematic issue regarding an insufficient base of the conception of learning outcomes in the Bloom's taxonomy affective domain. The search for solutions introduces the conception of teaching and learning in the affective domain as well as presents validity criteria of learning outcomes in the affective domain. The…

  16. 32 CFR 644.534 - Return of public domain land.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 4 2011-07-01 2011-07-01 false Return of public domain land. 644.534 Section... Excess Land and Improvements § 644.534 Return of public domain land. (a) General. The procedures... on or in the land after release are equally applicable to public domain lands. Air Force policy...

  17. The Dynamic Interdependence of Developmental Domains across Emerging Adulthood

    ERIC Educational Resources Information Center

    Sneed, Joel R.; Hamagami, Fumiaki; McArdle, John J.; Cohen, Patricia; Chen, Henian

    2007-01-01

    Emerging adulthood is a period in which profound role changes take place across a number of life domains including finance, romance, and residence. On the basis of dynamic systems theory, change in one domain should be related to change in another domain, because the concept of development according to this approach is a relational one. To…

  18. A Methodology to Develop Ontologies for Emerging Domains

    ERIC Educational Resources Information Center

    Meenorngwar, Chai

    2013-01-01

    The characteristic of complex, dynamic domains, such as an emerging domain, is that the information necessary to describe them is not fully established. Standards are not yet established for these domains, and hence they are difficult to describe and present, and methods are needed that will reflect the changes that will occur as the domains…

  19. Between- and Within-Domain Relations of Students' Academic Emotions

    ERIC Educational Resources Information Center

    Goetz, Thomas; Frenzel, Anne C.; Pekrun, Reinhard; Hall, Nathan C.; Ludtke, Oliver

    2007-01-01

    The authors investigated between- and within-domain relations of academic emotions, including students' enjoyment, pride, anxiety, anger, and boredom experienced in mathematics, physics, German, and English classes (N = 542; Grades 8 and 11). Corroborating assumptions of domain specificity, the between-domains relations of these emotions were weak…

  20. Frequency-Domain Methods for Characterization of Pulsed Power Diagnostics

    SciTech Connect

    White, A D; Anderson, R A; Ferriera, T J; Goerz, D A

    2009-07-27

    This paper discusses methods of frequency-domain characterization of pulsed power sensors using vector network analyzer and spectrum analyzer techniques that offer significant simplification over time-domain methods, while mitigating or minimizing the effect of the difficulties present in time domain characterization. These methods are applicable to characterization of a wide variety of sensors.