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Sample records for a2 domain facilitate

  1. Do proteins facilitate the formation of cholesterol-rich domains?

    PubMed

    Epand, Richard M

    2004-11-03

    Both biological and model membranes can exhibit the formation of domains. A brief review of some of the diverse methodologies used to identify the presence of domains in membranes is given. Some of these domains are enriched in cholesterol. The segregation of lipids into cholesterol-rich domains can occur in both pure lipid systems as well as membranes containing peptides and proteins. Peptides and proteins can promote the formation of cholesterol-rich domains not only by preferentially interacting with cholesterol and being sequestered into these regions of the membrane, but also indirectly as a consequence of being excluded from cholesterol-rich domains. The redistribution of components is dictated by the thermodynamics of the system. The formation of domains in a biological membrane is a consequence of all of the intermolecular interactions including those among lipid molecules as well as between lipids and proteins.

  2. Facilitation of Ferroelectric Switching via Mechanical Manipulation of Hierarchical Nanoscale Domain Structures

    NASA Astrophysics Data System (ADS)

    Chen, Zibin; Hong, Liang; Wang, Feifei; Ringer, Simon P.; Chen, Long-Qing; Luo, Haosu; Liao, Xiaozhou

    2017-01-01

    Heterogeneous ferroelastic transition that produces hierarchical 90° tetragonal nanodomains via mechanical loading and its effect on facilitating ferroelectric domain switching in relaxor-based ferroelectrics were explored. Combining in situ electron microscopy characterization and phase-field modeling, we reveal the nature of the transition process and discover that the transition lowers by 40% the electrical loading threshold needed for ferroelectric domain switching. Our results advance the fundamental understanding of ferroelectric domain switching behavior.

  3. Facilitation of Ferroelectric Switching via Mechanical Manipulation of Hierarchical Nanoscale Domain Structures.

    PubMed

    Chen, Zibin; Hong, Liang; Wang, Feifei; Ringer, Simon P; Chen, Long-Qing; Luo, Haosu; Liao, Xiaozhou

    2017-01-06

    Heterogeneous ferroelastic transition that produces hierarchical 90° tetragonal nanodomains via mechanical loading and its effect on facilitating ferroelectric domain switching in relaxor-based ferroelectrics were explored. Combining in situ electron microscopy characterization and phase-field modeling, we reveal the nature of the transition process and discover that the transition lowers by 40% the electrical loading threshold needed for ferroelectric domain switching. Our results advance the fundamental understanding of ferroelectric domain switching behavior.

  4. Domain loss facilitates accelerated evolution and neofunctionalization of duplicate snake venom metalloproteinase toxin genes.

    PubMed

    Casewell, Nicholas R; Wagstaff, Simon C; Harrison, Robert A; Renjifo, Camila; Wüster, Wolfgang

    2011-09-01

    Gene duplication is a key mechanism for the adaptive evolution and neofunctionalization of gene families. Large multigene families often exhibit complex evolutionary histories as a result of frequent gene duplication acting in concordance with positive selection pressures. Alterations in the domain structure of genes, causing changes in the molecular scaffold of proteins, can also result in a complex evolutionary history and has been observed in functionally diverse multigene toxin families. Here, we investigate the role alterations in domain structure have on the tempo of evolution and neofunctionalization of multigene families using the snake venom metalloproteinases (SVMPs) as a model system. Our results reveal that the evolutionary history of viperid (Serpentes: Viperidae) SVMPs is repeatedly punctuated by domain loss, with the single loss of the cysteine-rich domain, facilitating the formation of P-II class SVMPs, occurring prior to the convergent loss of the disintegrin domain to form multiple P-I SVMP structures. Notably, the majority of phylogenetic branches where domain loss was inferred to have occurred exhibited highly significant evidence of positive selection in surface-exposed amino acid residues, resulting in the neofunctionalization of P-II and P-I SVMP classes. These results provide a valuable insight into the mechanisms by which complex gene families evolve and detail how the loss of domain structures can catalyze the accelerated evolution of novel gene paralogues. The ensuing generation of differing molecular scaffolds encoded by the same multigene family facilitates gene neofunctionalization while presenting an evolutionary advantage through the retention of multiple genes capable of encoding functionally distinct proteins.

  5. Functional Equivalence of Retroviral MA Domains in Facilitating Psi RNA Binding Specificity by Gag

    PubMed Central

    Rye-McCurdy, Tiffiny; Olson, Erik D.; Liu, Shuohui; Binkley, Christiana; Reyes, Joshua-Paolo; Thompson, Brian R.; Flanagan, John M.; Parent, Leslie J.; Musier-Forsyth, Karin

    2016-01-01

    Retroviruses specifically package full-length, dimeric genomic RNA (gRNA) even in the presence of a vast excess of cellular RNA. The “psi” (Ψ) element within the 5′-untranslated region (5′UTR) of gRNA is critical for packaging through interaction with the nucleocapsid (NC) domain of Gag. However, in vitro Gag binding affinity for Ψ versus non-Ψ RNAs is not significantly different. Previous salt-titration binding assays revealed that human immunodeficiency virus type 1 (HIV-1) Gag bound to Ψ RNA with high specificity and relatively few charge interactions, whereas binding to non-Ψ RNA was less specific and involved more electrostatic interactions. The NC domain was critical for specific Ψ binding, but surprisingly, a Gag mutant lacking the matrix (MA) domain was less effective at discriminating Ψ from non-Ψ RNA. We now find that Rous sarcoma virus (RSV) Gag also effectively discriminates RSV Ψ from non-Ψ RNA in a MA-dependent manner. Interestingly, Gag chimeras, wherein the HIV-1 and RSV MA domains were swapped, maintained high binding specificity to cognate Ψ RNAs. Using Ψ RNA mutant constructs, determinants responsible for promoting high Gag binding specificity were identified in both systems. Taken together, these studies reveal the functional equivalence of HIV-1 and RSV MA domains in facilitating Ψ RNA selectivity by Gag, as well as Ψ elements that promote this selectivity. PMID:27657107

  6. Thermocapillary bubble dynamics in a 2D axis swirl domain

    NASA Astrophysics Data System (ADS)

    Alhendal, Yousuf; Turan, Ali

    2014-09-01

    The lack of significant buoyancy effects in zero-gravity conditions poses an issue with fluid transfer in a stagnant liquid. In this paper, bubble movement in a stagnant liquid is analysed and presented numerically using a computational fluid dynamics approach. The governing continuum and conservation equations for two-phase flow are solved using the commercial software package Ansys-Fluent v.13. The volume of fluid method is used to track the liquid/gas interface in 2D and 3D domains, which has been found to be a valuable tool for studying the phenomenon of gas-liquid interaction, and the validation results are in reasonable agreement with earlier experimental observations. The flow is driven via Marangoni influence induced by the temperature difference, which in turn drives the bubble from the cold to the hot region. The results indicate that the inherent velocity of bubbles decreases with an increase in Marangoni number; this is in agreement with the results of previous experiments conducted in Kang et al. (Microgravity Sci Technol 20:67-71, 2008). Some three-dimensional simulations will also be performed to compare and examine the results with two-dimensional simulations. The thermocapillary bubble flow in a 2D swirl axisymmetry driven by the rotation of the walls was also carried out for different angular velocities in zero gravity. The bubble migration speed was found to decrease with increasing angular velocity. This occurrence is due to an increase in the pressure gradient between the cylinder's outer wall and the axis of rotation, which forces the lowest pressure region to shift from the sides of the bubble to the axis of rotation. A deformation of the bubble and the formation of the two vortices inside the bubble are also observed. These new and original findings aim to help support research into space applications.

  7. Thermocapillary bubble dynamics in a 2D axis swirl domain

    NASA Astrophysics Data System (ADS)

    Alhendal, Yousuf; Turan, Ali

    2015-04-01

    The lack of significant buoyancy effects in zero-gravity conditions poses an issue with fluid transfer in a stagnant liquid. In this paper, bubble movement in a stagnant liquid is analysed and presented numerically using a computational fluid dynamics approach. The governing continuum and conservation equations for two-phase flow are solved using the commercial software package Ansys-Fluent v.13. The volume of fluid method is used to track the liquid/gas interface in 2D and 3D domains, which has been found to be a valuable tool for studying the phenomenon of gas-liquid interaction, and the validation results are in reasonable agreement with earlier experimental observations. The flow is driven via Marangoni influence induced by the temperature difference, which in turn drives the bubble from the cold to the hot region. The results indicate that the inherent velocity of bubbles decreases with an increase in Marangoni number; this is in agreement with the results of previous experiments conducted in Kang et al. (Microgravity Sci Technol 20:67-71, 2008). Some three-dimensional simulations will also be performed to compare and examine the results with two-dimensional simulations. The thermocapillary bubble flow in a 2D swirl axisymmetry driven by the rotation of the walls was also carried out for different angular velocities in zero gravity. The bubble migration speed was found to decrease with increasing angular velocity. This occurrence is due to an increase in the pressure gradient between the cylinder's outer wall and the axis of rotation, which forces the lowest pressure region to shift from the sides of the bubble to the axis of rotation. A deformation of the bubble and the formation of the two vortices inside the bubble are also observed. These new and original findings aim to help support research into space applications.

  8. Ligand-binding domains of nuclear receptors facilitate tight control of split CRISPR activity

    PubMed Central

    Nguyen, Duy P.; Miyaoka, Yuichiro; Gilbert, Luke A.; Mayerl, Steven J.; Lee, Brian H.; Weissman, Jonathan S.; Conklin, Bruce R.; Wells, James A.

    2016-01-01

    Cas9-based RNA-guided nuclease (RGN) has emerged to be a versatile method for genome editing due to the ease of construction of RGN reagents to target specific genomic sequences. The ability to control the activity of Cas9 with a high temporal resolution will facilitate tight regulation of genome editing processes for studying the dynamics of transcriptional regulation or epigenetic modifications in complex biological systems. Here we show that fusing ligand-binding domains of nuclear receptors to split Cas9 protein fragments can provide chemical control over split Cas9 activity. The method has allowed us to control Cas9 activity in a tunable manner with no significant background, which has been challenging for other inducible Cas9 constructs. We anticipate that our design will provide opportunities through the use of different ligand-binding domains to enable multiplexed genome regulation of endogenous genes in distinct loci through simultaneous chemical regulation of orthogonal Cas9 variants. PMID:27363581

  9. Extremely long range chromatin loops link topological domains to facilitate a diverse antibody repertoire

    PubMed Central

    Montefiori, Lindsey; Wuerffel, Robert; Roqueiro, Damian; Lajoie, Bryan; Guo, Changying; Gerasimova, Tatiana; De, Supriyo; Wood, William; Becker, Kevin G.; Dekker, Job; Liang, Jie; Sen, Ranjan; Kenter, Amy L.

    2015-01-01

    SUMMARY Early B cell development is characterized by large scale Igh locus contraction prior to V(D)J recombination to facilitate a highly diverse Ig repertoire. However, an understanding of the molecular architecture that mediates locus contraction remains unclear. We have combined high resolution chromosome conformation capture (3C) techniques with 3D DNA FISH to identify three conserved topological sub-domains. Each of these topological folds encompasses a major VH gene family that become juxtaposed in pro-B cells via Mb-scale chromatin looping. The transcription factor Pax5 organizes the sub-domain that spans the VHJ558 gene family. In its absence the J558 VH genes fail to associate with the proximal VH genes, thereby providing a plausible explanation for reduced VHJ558 gene rearrangements in Pax5-deficient pro-B cells. We propose that Igh locus contraction is the cumulative effect of several independently controlled chromatin sub-domains that provide the structural infrastructure to coordinate optimal antigen receptor assembly. PMID:26804913

  10. BAR Domain-Containing FAM92 Proteins Interact with Chibby1 To Facilitate Ciliogenesis

    PubMed Central

    Li, Feng-Qian; Chen, Xingwang; Fisher, Cody; Siller, Saul S.; Zelikman, Klara; Kuriyama, Ryoko

    2016-01-01

    Chibby1 (Cby1) is a small, conserved coiled-coil protein that localizes to centrioles/basal bodies and plays a crucial role in the formation and function of cilia. During early stages of ciliogenesis, Cby1 is required for the efficient recruitment of small vesicles at the distal end of centrioles to facilitate basal body docking to the plasma membrane. Here, we identified family with sequence similarity 92, member A (FAM92A) and FAM92B, which harbor predicted lipid-binding BAR domains, as novel Cby1-interacting partners using tandem affinity purification and mass spectrometry. We found that in cultured cell lines, FAM92A colocalizes with Cby1 at the centrioles/basal bodies of primary cilia, while FAM92B is undetectable. In airway multiciliated cells, both FAM92A and -92B colocalize with Cby1 at the base of cilia. Notably, the centriolar localization of FAM92A and -92B depends largely on Cby1. Knockdown of FAM92A in RPE1 cells impairs ciliogenesis. Consistent with the membrane-remodeling properties of BAR domains, FAM92A and -92B in cooperation with Cby1 induce deformed membrane-like structures containing the small GTPase Rab8 in cultured cells. Our results therefore suggest that FAM92 proteins interact with Cby1 to promote ciliogenesis via regulation of membrane-remodeling processes. PMID:27528616

  11. A role of the SAM domain in EphA2 receptor activation

    PubMed Central

    Shi, Xiaojun; Hapiak, Vera; Zheng, Ji; Muller-Greven, Jeannine; Bowman, Deanna; Lingerak, Ryan; Buck, Matthias; Wang, Bing-Cheng; Smith, Adam W.

    2017-01-01

    Among the 20 subfamilies of protein receptor tyrosine kinases (RTKs), Eph receptors are unique in possessing a sterile alpha motif (SAM domain) at their C-terminal ends. However, the functions of SAM domains in Eph receptors remain elusive. Here we report on a combined cell biology and quantitative fluorescence study to investigate the role of the SAM domain in EphA2 function. We observed elevated tyrosine autophosphorylation levels upon deletion of the EphA2 SAM domain (EphA2ΔS) in DU145 and PC3 prostate cancer cells and a skin tumor cell line derived from EphA1/A2 knockout mice. These results suggest that SAM domain deletion induced constitutive activation of EphA2 kinase activity. In order to explain these effects, we applied fluorescence correlation spectroscopy to investigate the lateral molecular organization of EphA2. Our results indicate that SAM domain deletion (EphA2ΔS-GFP) increases oligomerization compared to the full length receptor (EphA2FL-GFP). Stimulation with ephrinA1, a ligand for EphA2, induced further oligomerization and activation of EphA2FL-GFP. The SAM domain deletion mutant, EphA2ΔS-GFP, also underwent further oligomerization upon ephrinA1 stimulation, but the oligomers were larger than those observed for EphA2FL-GFP. Based on these results, we conclude that the EphA2 SAM domain inhibits kinase activity by reducing receptor oligomerization. PMID:28338017

  12. Computer-predicted peptides that mimic discontinuous epitopes on the A2 domain of factor VIII.

    PubMed

    Lebreton, A; Simon, N; Moreau, V; Demolombe, V; Cayzac, C; Nguyen, C; Schved, J F; Granier, C; Lavigne-Lissalde, G

    2015-05-01

    Development of antibodies (Abs) against factor VIII (FVIII) is a severe complication of haemophilia A treatment. Recent publications suggest that domain specificity of anti-FVIII antibodies, particularly during immune tolerance induction (ITI), might be related to the outcome of the treatment. Obtaining suitable tools for a fine mapping of discontinuous epitopes could thus be helpful. The aim of this study was to map discontinuous epitopes on FVIII A2 domain using a new epitope prediction functionality of the PEPOP bioinformatics tool and a peptide inhibition assay based on the Luminex technology. We predicted, selected and synthesized 40 peptides mimicking discontinuous epitopes on the A2 domain of FVIII. A new inhibition assays using Luminex technology was performed to identify peptides able to inhibit the binding of anti-A2 Abs to A2 domain. We identified two peptides (IFKKLYHVWTKEVG and LYSRRLPKGVKHFD) able to block the binding of anti-A2 allo-antibodies to this domain. The three-dimensional representation of these two peptides on the A2 domain revealed that they are localized on a limited region of A2. We also confirmed that residues 484-508 of the A2 domain define an antigenic site. We suggest that dissection of the antibody response during ITI using synthetic peptide epitopes could provide important information for the management of patients with inhibitors.

  13. Use of Heuristics to Facilitate Scientific Discovery Learning in a Simulation Learning Environment in a Physics Domain

    ERIC Educational Resources Information Center

    Veermans, Koen; van Joolingen, Wouter; de Jong, Ton

    2006-01-01

    This article describes a study into the role of heuristic support in facilitating discovery learning through simulation-based learning. The study compares the use of two such learning environments in the physics domain of collisions. In one learning environment (implicit heuristics) heuristics are only used to provide the learner with guidance…

  14. Discoidin domain receptor 2 facilitates prostate cancer bone metastasis via regulating parathyroid hormone-related protein.

    PubMed

    Yan, Zhang; Jin, Su; Wei, Zhang; Huilian, Hou; Zhanhai, Yin; Yue, Teng; Juan, Li; Jing, Li; Libo, Yao; Xu, Li

    2014-09-01

    Prostate cancer frequently metastasizes to the skeleton but the underlying mechanism remains largely undefined. Discoidin domain receptor 2 (DDR2) is a member of receptor tyrosine kinase (RTK) family and is activated by collagen binding. This study aimed to investigate the function and detailed mechanism of DDR2 in prostate cancer bone dissemination. Herein we found that DDR2 was strongly expressed in bone-metastatic prostate cancer cells and tissues compared to that in normal controls. Enhanced expression of constitutively activated DDR2 led to elevation in motility and invasiveness of prostate cancer cells, whereas knockdown of DDR2 through specific shRNA caused a dramatic repression. Knockdown of DDR2 in prostate cancer cells resulted in significant decrease in the proliferation, differentiation and function of osteoblast. Over-expression of DDR2 in prostate cancer cells resulted in notable acceleration of osteoclast differentiation and bone resorption, whereas knockdown of DDR2 exhibited the opposite effects. An intrabone injection bone metastasis animal model demonstrated that DDR2 promoted osteolytic metastasis in vivo. Molecular evidence demonstrated that DDR2 regulated the expression, secretion, and promoter activity of parathyroid hormone-related protein (PTHrP), via modulating Runx2 phosphorylation and transactivity. DDR2 was responsive to TGF-β and involved in TGF-β-mediated osteoclast activation and bone resorption. In addition, DDR2 facilitated prostate cancer cells adhere to type I collagen. This study reveals for the first time that DDR2 plays an essential role in prostate cancer bone metastasis. The mechanism disclosure may provide therapeutic targets for the treatment of prostate cancer.

  15. The BAH domain facilitates the ability of human Orc1 protein to activate replication origins in vivo

    PubMed Central

    Noguchi, Kohji; Vassilev, Alex; Ghosh, Soma; Yates, John L; DePamphilis, Melvin L

    2006-01-01

    Selection of initiation sites for DNA replication in eukaryotes is determined by the interaction between the origin recognition complex (ORC) and genomic DNA. In mammalian cells, this interaction appears to be regulated by Orc1, the only ORC subunit that contains a bromo-adjacent homology (BAH) domain. Since BAH domains mediate protein–protein interactions, the human Orc1 BAH domain was mutated, and the mutant proteins expressed in human cells to determine their affects on ORC function. The BAH domain was not required for nuclear localization of Orc1, association of Orc1 with other ORC subunits, or selective degradation of Orc1 during S-phase. It did, however, facilitate reassociation of Orc1 with chromosomes during the M to G1-phase transition, and it was required for binding Orc1 to the Epstein–Barr virus oriP and stimulating oriP-dependent plasmid DNA replication. Moreover, the BAH domain affected Orc1's ability to promote binding of Orc2 to chromatin as cells exit mitosis. Thus, the BAH domain in human Orc1 facilitates its ability to activate replication origins in vivo by promoting association of ORC with chromatin. PMID:17066079

  16. The Robustness of a Signaling Complex to Domain Rearrangements Facilitates Network Evolution

    PubMed Central

    Sato, Paloma M.; Yoganathan, Kogulan; Jung, Jae H.; Peisajovich, Sergio G.

    2014-01-01

    The rearrangement of protein domains is known to have key roles in the evolution of signaling networks and, consequently, is a major tool used to synthetically rewire networks. However, natural mutational events leading to the creation of proteins with novel domain combinations, such as in frame fusions followed by domain loss, retrotranspositions, or translocations, to name a few, often simultaneously replace pre-existing genes. Thus, while proteins with new domain combinations may establish novel network connections, it is not clear how the concomitant deletions are tolerated. We investigated the mechanisms that enable signaling networks to tolerate domain rearrangement-mediated gene replacements. Using as a model system the yeast mitogen activated protein kinase (MAPK)-mediated mating pathway, we analyzed 92 domain-rearrangement events affecting 11 genes. Our results indicate that, while domain rearrangement events that result in the loss of catalytic activities within the signaling complex are not tolerated, domain rearrangements can drastically alter protein interactions without impairing function. This suggests that signaling complexes can maintain function even when some components are recruited to alternative sites within the complex. Furthermore, we also found that the ability of the complex to tolerate changes in interaction partners does not depend on long disordered linkers that often connect domains. Taken together, our results suggest that some signaling complexes are dynamic ensembles with loose spatial constraints that could be easily re-shaped by evolution and, therefore, are ideal targets for cellular engineering. PMID:25490747

  17. Use of Heuristics to Facilitate Scientific Discovery Learning in a Simulation Learning Environment in a Physics Domain

    NASA Astrophysics Data System (ADS)

    Veermans, Koen; van Joolingen, Wouter; de Jong, Ton

    2006-03-01

    This article describes a study into the role of heuristic support in facilitating discovery learning through simulation-based learning. The study compares the use of two such learning environments in the physics domain of collisions. In one learning environment (implicit heuristics) heuristics are only used to provide the learner with guidance derived from heuristics, without presenting the heuristics themselves; in the other (explicit heuristics) the heuristics themselves are also made explicit to the learner. The two learning environments are tested with 46 students from two schools. The results show that learners in both conditions gain domain knowledge from pre-test to post-test. Regression analyses show that pre-test results can predict post-test results in the implicit heuristics condition but not in the explicit heuristic condition. Process analyses suggest that presenting the heuristics explicitly facilitate more self-regulation in students.

  18. Modeling of leachate generation from MSW landfills by a 2-dimensional 2-domain approach

    SciTech Connect

    Fellner, Johann

    2010-11-15

    The flow of water through Municipal Solid Waste (MSW) landfills is highly non-uniform and dominated by preferential pathways. Thus, concepts to simulate landfill behavior require that a heterogeneous flow regime is considered. Recent models are based on a 2-domain approach, differentiating between channel domain with high hydraulic conductivity, and matrix domain of slow water movement with high water retention capacity. These models focus on the mathematical description of rapid water flow in channel domain. The present paper highlights the importance of water exchange between the two domains, and expands the 1-dimensional, 2-domain flow model by taking into account water flows in two dimensions. A flow field consisting of a vertical path (channel domain) surrounded by the waste mass (matrix domain) is defined using the software HYDRUS-2D. When the new model is calibrated using data sets from a MSW-landfill site the predicted leachate generation corresponds well with the observed leachate discharge. An overall model efficiency in terms of r{sup 2} of 0.76 was determined for a simulation period of almost 4 years. The results confirm that water in landfills follows a preferential path way characterized by high permeability (K{sub s} = 300 m/d) and zero retention capacity, while the bulk of the landfill (matrix domain) is characterized by low permeability (K{sub s} = 0.1 m/d) and high retention capacity. The most sensitive parameters of the model are the hydraulic conductivities of the channel domain and the matrix domain, and the anisotropy of the matrix domain.

  19. The Sec7 N-terminal regulatory domains facilitate membrane-proximal activation of the Arf1 GTPase

    PubMed Central

    Richardson, Brian C; Halaby, Steve L; Gustafson, Margaret A; Fromme, J Christopher

    2016-01-01

    The Golgi complex is the central sorting compartment of eukaryotic cells. Arf guanine nucleotide exchange factors (Arf-GEFs) regulate virtually all traffic through the Golgi by activating Arf GTPase trafficking pathways. The Golgi Arf-GEFs contain multiple autoregulatory domains, but the precise mechanisms underlying their function remain largely undefined. We report a crystal structure revealing that the N-terminal DCB and HUS regulatory domains of the Arf-GEF Sec7 form a single structural unit. We demonstrate that the established role of the N-terminal region in dimerization is not conserved; instead, a C-terminal autoinhibitory domain is responsible for dimerization of Sec7. We find that the DCB/HUS domain amplifies the ability of Sec7 to activate Arf1 on the membrane surface by facilitating membrane insertion of the Arf1 amphipathic helix. This enhancing function of the Sec7 N-terminal domains is consistent with the high rate of Arf1-dependent trafficking to the plasma membrane necessary for maximal cell growth. DOI: http://dx.doi.org/10.7554/eLife.12411.001 PMID:26765562

  20. Polymerization of immunoglobulin domains: A model system for the development of facilitated macromolecular assembly

    SciTech Connect

    Stevens, F.J.; Myatt, E.A.

    1991-12-31

    We have recently determined that monoclonal immunoglobulin light chains (Bence Jones proteins) are capable of reversible polymerization at room temperature. This property, as exhibited by immunoglobulin light chains (normally a component of an intact antibody molecule), may have novel implications for the development of ``molecular nanotechnology.`` The polymerization capability of the immunoglobulin light chain is associated with the so-called variable domain of this molecule. The variable domain is a durable, compact beta-sheet structure of molecular weight approximately 12,000. Most of the primary sequence variation is limited to one portion of the molecule, that portion associated with the contribution of immunoglobulin light chains to the recognition and binding of thousand of different antigens by antibodies. As a consequence of these variations, different light chains polymerize with different degrees of avidity, from negligible to extensive. The polymerization process depends on solution parameters such as Ph. Thus, polymerization might be induced at one pH and suppressed or reversed at another. Combinations of molecules of appropriate specificities could assemble into structures of predetermined three-dimensional forms and properties. These features suggest that Bence Jones proteins represent a powerful model system within which to develop empirical rules relevant to a technology of protein-based ``construction``. Development of these rules will require the combined efforts of biophysical and crystallographic studies, protein engineering, and molecular modeling. 53 refs., 5 figs.

  1. Polymerization of immunoglobulin domains: A model system for the development of facilitated macromolecular assembly

    SciTech Connect

    Stevens, F.J.; Myatt, E.A.

    1991-01-01

    We have recently determined that monoclonal immunoglobulin light chains (Bence Jones proteins) are capable of reversible polymerization at room temperature. This property, as exhibited by immunoglobulin light chains (normally a component of an intact antibody molecule), may have novel implications for the development of molecular nanotechnology.'' The polymerization capability of the immunoglobulin light chain is associated with the so-called variable domain of this molecule. The variable domain is a durable, compact beta-sheet structure of molecular weight approximately 12,000. Most of the primary sequence variation is limited to one portion of the molecule, that portion associated with the contribution of immunoglobulin light chains to the recognition and binding of thousand of different antigens by antibodies. As a consequence of these variations, different light chains polymerize with different degrees of avidity, from negligible to extensive. The polymerization process depends on solution parameters such as Ph. Thus, polymerization might be induced at one pH and suppressed or reversed at another. Combinations of molecules of appropriate specificities could assemble into structures of predetermined three-dimensional forms and properties. These features suggest that Bence Jones proteins represent a powerful model system within which to develop empirical rules relevant to a technology of protein-based construction''. Development of these rules will require the combined efforts of biophysical and crystallographic studies, protein engineering, and molecular modeling. 53 refs., 5 figs.

  2. Leveraging domain knowledge to facilitate visual exploration of large population datasets.

    PubMed

    Hsu, William; Bui, Alex A T

    2013-01-01

    Observational patient data provides an unprecedented opportunity to gleam new insights into diseases and assess patient quality of care, but a challenge lies in matching our ability to collect data with a comparable ability to understand and apply this information. Visual analytic techniques are promising as they permit the exploration and manipulation of complex datasets through a graphical user interface. Nevertheless, current visualization tools rely on users to manually configure which aspects of the dataset are shown and how they are presented. In this paper, we describe an approach that utilizes characteristics of the data and domain knowledge to assist users with summarizing the information space of a large population. We present a representation that captures contextual information about the data and constructs that operate on this information to tailor the data's presentation. We describe a use case of this approach in exploring a claims dataset of individuals with spinal dysraphism.

  3. Modeling Tear Film Dynamics on a 2-D Eye-shaped Domain

    NASA Astrophysics Data System (ADS)

    Li, Longfei; Braun, Richard; Maki, Kara; Henshaw, William

    2012-11-01

    We study tear film dynamics on a 2-D eye-shaped domain using a lubrication model. Time dependent flux boundary conditions that model the lacrimal gland tear supply and punctal drainage are imposed. We solved the model equations with Overture computational framework. Results reveals our model captures the hydraulic connectivity and other key physics of human tear film observed in vivo. Comparisons are made with existing models and experiments. Should time permit, osmolarity dynamics (salt ion concentration) will be included.

  4. The Sec domain protein Scfd1 facilitates trafficking of ECM components during chondrogenesis.

    PubMed

    Hou, Ningning; Yang, Yuxi; Scott, Ian C; Lou, Xin

    2017-01-01

    Chondrogenesis in the developing skeleton requires transformation of chondrocytes from a simple mesenchymal condensation to cells with a highly enriched extracellular matrix (ECM). This transition is in part accomplished by alterations in the chondrocyte protein transport machinery to cope with both the increased amount and large size of ECM components. In a zebrafish mutagenesis screen to identify genes essential for cartilage development, we uncovered a mutant that disrupts the gene encoding Sec1 family domain containing 1 (scfd1). Homozygous scfd1 mutant embryos exhibit a profound craniofacial abnormality caused by a failure of chondrogenesis. Loss of scfd1 was found to hinder ER to Golgi transport of ECM proteins and is accompanied with activation of the unfolded protein response in chondrocytes. We further demonstrate a conserved role for Scfd1 in differentiation of mammalian chondrocytes, in which loss of either SCFD1 or STX18, a SLY1 interacting t-SNARE, severely impair transport of type II collagen. These results show that the existence of a specific export pathway, mediated by a complex containing SCFD1 and STX18 that plays an essential role in secretion of large ECM proteins during chondrogenesis.

  5. Finite-difference time-domain-based optical microscopy simulation of dispersive media facilitates the development of optical imaging techniques

    NASA Astrophysics Data System (ADS)

    Zhang, Di; Capoglu, Ilker; Li, Yue; Cherkezyan, Lusik; Chandler, John; Spicer, Graham; Subramanian, Hariharan; Taflove, Allen; Backman, Vadim

    2016-06-01

    Combining finite-difference time-domain (FDTD) methods and modeling of optical microscopy modalities, we previously developed an open-source software package called Angora, which is essentially a "microscope in a computer." However, the samples being simulated were limited to nondispersive media. Since media dispersions are common in biological samples (such as cells with staining and metallic biomarkers), we have further developed a module in Angora to simulate samples having complicated dispersion properties, thereby allowing the synthesis of microscope images of most biological samples. We first describe a method to integrate media dispersion into FDTD, and we validate the corresponding Angora dispersion module by applying Mie theory, as well as by experimentally imaging gold microspheres. Then, we demonstrate how Angora can facilitate the development of optical imaging techniques with a case study.

  6. Membrane Restructuring by Phospholipase A2 Is Regulated by the Presence of Lipid Domains

    PubMed Central

    Leidy, Chad; Ocampo, Jackson; Duelund, Lars; Mouritsen, Ole G.; Jørgensen, Kent; Peters, Günther H.

    2011-01-01

    Secretory phospholipase A2 (sPLA2) catalyzes the hydrolysis of glycerophospholipids. This enzyme is sensitive to membrane structure, and its activity has been shown to increase in the presence of liquid-crystalline/gel (Lα/Lβ) lipid domains. In this work, we explore whether lipid domains can also direct the activity of the enzyme by inducing hydrolysis of certain lipid components due to preferential activity of the enzyme toward lipid domains susceptible to sPLA2. Specifically, we show that the presence of Lα/Lβ and Lα/Pβ′ phase coexistence in a 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC)/1,2 distearoyl-sn-glycero-3-phosphocholine (DSPC) system results in the preferential hydrolysis of the shorter-chained lipid component in the mixture, leading to an enrichment in the longer-chained component. The restructuring process is monitored by atomic force microscopy on supported single and double bilayers formed by vesicle fusion. We observe that during preferential hydrolysis of the DMPC-rich Lα regions, the Lβ and Pβ′ regions grow and reseal, maintaining membrane integrity. This result indicates that a sharp reorganization of the membrane structure can occur during sPLA2 hydrolysis without necessarily destroying the membrane. We confirm by high-performance liquid chromatography the preferential hydrolysis of DMPC within the phase coexistence region of the DMPC/DSPC phase diagram, showing that this preferential hydrolysis is accentuated close to the solidus phase boundary. Differential scanning calorimetry results show that this preferential hydrolysis in the presence of lipid domains leads to a membrane system with a higher-temperature melting profile due to enrichment in DSPC. Together, these results show that the presence of lipid domains can induce specificity in the hydrolytic activity of the enzyme, resulting in marked differences in the physical properties of the membrane end-product. PMID:21723818

  7. A Cholesterol Recognition Amino Acid Consensus Domain in GP64 Fusion Protein Facilitates Anchoring of Baculovirus to Mammalian Cells

    PubMed Central

    Luz-Madrigal, Agustin; Asanov, Alexander; Camacho-Zarco, Aldo R.; Sampieri, Alicia

    2013-01-01

    Baculoviridae is a large family of double-stranded DNA viruses that selectively infect insects. Autographa californica multiple nucleopolyhedrovirus (AcMNPV) is the best-studied baculovirus from the family. Many studies over the last several years have shown that AcMNPV can enter a wide variety of mammalian cells and deliver genetic material for foreign gene expression. While most animal viruses studied so far have developed sophisticated mechanisms to selectively infect specific cells and tissues in an organism, AcMNPV can penetrate and deliver foreign genes into most cells studied to this date. The details about the mechanisms of internalization have been partially described. In the present study, we have identified a cholesterol recognition amino acid consensus (CRAC) domain present in the AcMNPV envelope fusion protein GP64. We demonstrated the association of a CRAC domain with cholesterol, which is important to facilitate the anchoring of the virus at the mammalian cell membrane. Furthermore, this initial anchoring favors AcMNPV endocytosis via a dynamin- and clathrin-dependent mechanism. Under these conditions, efficient baculovirus-driven gene expression is obtained. In contrast, when cholesterol is reduced from the plasma membrane, AcMNPV enters the cell via a dynamin- and clathrin-independent mechanism. The result of using this alternative internalization pathway is a reduced level of baculovirus-driven gene expression. This study is the first to document the importance of a novel CRAC domain in GP64 and its role in modulating gene delivery in AcMNPV. PMID:23986592

  8. A cholesterol recognition amino acid consensus domain in GP64 fusion protein facilitates anchoring of baculovirus to mammalian cells.

    PubMed

    Luz-Madrigal, Agustin; Asanov, Alexander; Camacho-Zarco, Aldo R; Sampieri, Alicia; Vaca, Luis

    2013-11-01

    Baculoviridae is a large family of double-stranded DNA viruses that selectively infect insects. Autographa californica multiple nucleopolyhedrovirus (AcMNPV) is the best-studied baculovirus from the family. Many studies over the last several years have shown that AcMNPV can enter a wide variety of mammalian cells and deliver genetic material for foreign gene expression. While most animal viruses studied so far have developed sophisticated mechanisms to selectively infect specific cells and tissues in an organism, AcMNPV can penetrate and deliver foreign genes into most cells studied to this date. The details about the mechanisms of internalization have been partially described. In the present study, we have identified a cholesterol recognition amino acid consensus (CRAC) domain present in the AcMNPV envelope fusion protein GP64. We demonstrated the association of a CRAC domain with cholesterol, which is important to facilitate the anchoring of the virus at the mammalian cell membrane. Furthermore, this initial anchoring favors AcMNPV endocytosis via a dynamin- and clathrin-dependent mechanism. Under these conditions, efficient baculovirus-driven gene expression is obtained. In contrast, when cholesterol is reduced from the plasma membrane, AcMNPV enters the cell via a dynamin- and clathrin-independent mechanism. The result of using this alternative internalization pathway is a reduced level of baculovirus-driven gene expression. This study is the first to document the importance of a novel CRAC domain in GP64 and its role in modulating gene delivery in AcMNPV.

  9. Facilitated extinction of morphine conditioned place preference with Tat-GluA2(3Y) interference peptide.

    PubMed

    Dias, C; Wang, Y T; Phillips, A G

    2012-08-01

    Neuroplasticity including long-term depression (LTD) has been implicated in both learning processes and addiction. LTD can be blocked by intravenous administration of the interference peptide Tat-GluA2(3Y) that prevents regulated endocytosis of the alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) receptor. In this study, Tat-GluA2(3Y) was used to assess the role of LTD in the induction, expression, extinction and reinstatement of morphine-induced conditioned place preference (CPP). CPP was established in rats by pairing morphine (5 mg/kg, i.p.) or saline with a specific environmental context using a balanced protocol. Tat-GluA2(3Y) (0; 1.5; 2.25 nmol/g; i.v.), scrambled peptide (Tat-GluA2(Sc)), or vehicle was administered during the acquisition phase or prior to the test for CPP. Tat-GluA2(3Y) had no effect on the induction or initial expression of morphine-induced CPP. Rats that received Tat-GluA2(3Y) or Tat-GluA2(Sc) during acquisition were subsequently tested for 11 consecutive days in order to extinguish morphine CPP. CPP was then reinstated by an injection of morphine (5 mg/kg, i.p.). Co-administration of morphine and Tat-GluA2(3Y) during acquisition greatly facilitated extinction of CPP without affecting morphine-induced reinstatement of CPP. Using an intermittent retest schedule with bi-weekly tests to measure the maintenance of CPP, Tat-GluA2(3Y) during the acquisition phase had no effect on the maintenance of CPP. We propose that co-administration of Tat-GluA2(3Y) with morphine during acquisition of CPP weakens the association between morphine and contextual cues leading to rapid extinction of morphine CPP with repeated daily testing.

  10. Solution structure of the first Sam domain of Odin and binding studies with the EphA2 receptor.

    PubMed

    Mercurio, Flavia Anna; Marasco, Daniela; Pirone, Luciano; Pedone, Emilia Maria; Pellecchia, Maurizio; Leone, Marilisa

    2012-03-13

    The EphA2 receptor plays key roles in many physiological and pathological events, including cancer. The process of receptor endocytosis and the consequent degradation have attracted attention as possible means of overcoming the negative outcomes of EphA2 in cancer cells and decreasing tumor malignancy. A recent study indicates that Sam (sterile alpha motif) domains of Odin, a member of the ANKS (ankyrin repeat and sterile alpha motif domain-containing) family of proteins, are important for the regulation of EphA2 endocytosis. Odin contains two tandem Sam domains (Odin-Sam1 and -Sam2). Herein, we report on the nuclear magnetic resonance (NMR) solution structure of Odin-Sam1; through a variety of assays (employing NMR, surface plasmon resonance, and isothermal titration calorimetry techniques), we clearly demonstrate that Odin-Sam1 binds to the Sam domain of EphA2 in the low micromolar range. NMR chemical shift perturbation experiments and molecular modeling studies point out that the two Sam domains interact with a head-to-tail topology characteristic of several Sam-Sam complexes. This binding mode is similar to that we have previously proposed for the association between the Sam domains of the lipid phosphatase Ship2 and EphA2. This work further validates structural elements relevant for the heterotypic Sam-Sam interactions of EphA2 and provides novel insights for the design of potential therapeutic compounds that can modulate receptor endocytosis.

  11. C-type lectin-like domain and fibronectin-like type II domain of phospholipase A(2) receptor 1 modulate binding and migratory responses to collagen.

    PubMed

    Takahashi, Soichiro; Watanabe, Kazuhiro; Watanabe, Yosuke; Fujioka, Daisuke; Nakamura, Takamitsu; Nakamura, Kazuto; Obata, Jun-ei; Kugiyama, Kiyotaka

    2015-03-24

    Phospholipase A2 receptor 1 (PLA2R) mediates collagen-dependent migration. The mechanisms by which PLA2R interacts with collagen remain unclear. We produced HEK293 cells expressing full-length wild-type PLA2R or a truncated PLA2R that lacks fibronectin-like type II (FNII) domains or several regions of C-type lectin-like domain (CTLD). We show that the CTLD1-2 as well as the FNII domain of PLA2R are responsible for binding to collagen and for collagen-dependent migration. Thus, multiple regions and domains of the extracellular portion of PLA2R participate in the responses to collagen. These data suggest a potentially new mechanism for PLA2R-mediated biological response beyond that of a receptor for secretory PLA2.

  12. Intersubunit Physical Couplings Fostered By The Left Flipper Domain Facilitate Channel Opening Of P2X4 Receptors.

    PubMed

    Wang, Jin; Sun, Liang-Fei; Cui, Wen-Wen; Zhao, Wen-Shan; Ma, Xue-Fei; Li, Bin; Liu, Yan; Yang, Yang; Hu, You-Min; Huang, Li-Dong; Cheng, Xiao-Yang; Li, Lingyong; Lu, Xiang-Yang; Tian, Yun; Yu, Ye

    2017-03-16

    P2X receptors are ATP-gated trimeric channels with important roles in diverse pathophysiological functions. A detailed understanding of the mechanism underlying the gating process of these receptors is thus fundamentally important and may open new therapeutic avenues. The left flipper (LF) domain of P2X receptors is a flexible loop structure and its coordinated motions together with the dorsal fin (DF) domain are crucial for the channel gating of the P2X receptors. However, the mechanism underlying the crucial role of the LF domain in the channel gating remains obscure. Here, we propose that the ATP-induced allosteric changes of the LF domain enable it to foster intersubunit physical couplings among the DF and two lower body domains, which is pivotal for the channel gating of P2X4 receptors. Metadynamics analysis indicated that these newly established intersubunit couplings correlate well with the ATP-bound open state of the receptors. Moreover, weakening or strengthening these physical interactions with engineered intersubunit metal bridges remarkably decreased or increased the open probability of the receptors, respectively. Further disulfide crosslinking and covalent modification confirmed that the intersubunit physical couplings among the DF and two lower body domains fostered by the LF domain at the open state act as an integrated structural element that is stringently required for the channel gating of P2X4 receptors. Our observations provide new mechanistic insights into P2X receptor activation and will stimulate development of new allosteric modulators of P2X receptors.

  13. Valence-bond-solid domain walls in a 2D quantum magnet

    NASA Astrophysics Data System (ADS)

    Shao, Hui; Guo, Wenan; Sandvik, Anders

    sing quantum Monte Carlo simulations, we study properties of domain walls in a square-lattice S=1/2 Heisenberg model with additional interactions which can drive the system from an antiferromagnetic (AFM) ground state to a valence-bond solid (VBS). We study the finite-size scaling of the domain-wall energy at the putative ''deconfined'' critical AFM-VBS point, which gives access to the critical exponent governing the domain-wall width. This length-scale diverges faster than the correlation length and also is related to the scale of spinon deconfinement. Our results show additional evidence of deconfied quantum criticality and are compatible with critical exponents extracted from finite-size scaling of other quantities. NSFC Grant No. 11175018, NSF Grant No. DMR-1410126.

  14. N-linked glycans within the A2 domain of von Willebrand factor modulate macrophage-mediated clearance.

    PubMed

    Chion, Alain; O'Sullivan, Jamie M; Drakeford, Clive; Bergsson, Gudmundur; Dalton, Niall; Aguila, Sonia; Ward, Soracha; Fallon, Padraic G; Brophy, Teresa M; Preston, Roger J S; Brady, Lauren; Sheils, Orla; Laffan, Michael; McKinnon, Thomas A J; O'Donnell, James S

    2016-10-13

    Enhanced von Willebrand factor (VWF) clearance is important in the etiology of von Willebrand disease. However, the molecular mechanisms underlying VWF clearance remain poorly understood. In this study, we investigated the role of VWF domains and specific glycan moieties in regulating in vivo clearance. Our findings demonstrate that the A1 domain of VWF contains a receptor-recognition site that plays a key role in regulating the interaction of VWF with macrophages. In A1-A2-A3 and full-length VWF, this macrophage-binding site is cryptic but becomes exposed following exposure to shear or ristocetin. Previous studies have demonstrated that the N-linked glycans within the A2 domain play an important role in modulating susceptibility to ADAMTS13 proteolysis. We further demonstrate that these glycans presented at N1515 and N1574 also play a critical role in protecting VWF against macrophage binding and clearance. Indeed, loss of the N-glycan at N1515 resulted in markedly enhanced VWF clearance that was significantly faster than that observed with any previously described VWF mutations. In addition, A1-A2-A3 fragments containing the N1515Q or N1574Q substitutions also demonstrated significantly enhanced clearance. Importantly, clodronate-induced macrophage depletion significantly attenuated the increased clearance observed with N1515Q and N1574Q in both full-length VWF and A1-A2-A3. Finally, we further demonstrate that loss of these N-linked glycans does not enhance clearance in VWF in the presence of a structurally constrained A2 domain. Collectively, these novel findings support the hypothesis that conformation of the VWF A domains plays a critical role in modulating macrophage-mediated clearance of VWF in vivo.

  15. An artificially evolved albumin binding module facilitates chemical shift epitope mapping of GA domain interactions with phylogenetically diverse albumins.

    PubMed

    He, Yanan; Chen, Yihong; Rozak, David A; Bryan, Philip N; Orban, John

    2007-07-01

    Protein G-related albumin-binding (GA) modules occur on the surface of numerous Gram-positive bacterial pathogens and their presence may promote bacterial growth and virulence in mammalian hosts. We recently used phage display selection to evolve a GA domain, PSD-1 (phage selected domain-1), which tightly bound phylogenetically diverse albumins. With respect to PSD-1's broad albumin binding specificity, it remained unclear how the evolved binding epitope compared to those of naturally occurring GA domains and whether PSD-1's binding mode was the same for different albumins. We investigate these questions here using chemical shift perturbation measurements of PSD-1 with rabbit serum albumin (RSA) and human serum albumin (HSA) and put the results in the context of previous work on structure and dynamics of GA domains. Combined, these data provide insights into the requirements for broad binding specificity in GA-albumin interactions. Moreover, we note that using the phage-optimized PSD-1 protein significantly diminishes the effects of exchange broadening at the binding interface between GA modules and albumin, presumably through stabilization of a ligand-bound conformation. The employment of artificially evolved domains may be generally useful in NMR structural studies of other protein-protein complexes.

  16. Disease-Homologous Mutation in the Cation Diffusion Facilitator Protein MamM Causes Single-Domain Structural Loss and Signifies Its Importance

    PubMed Central

    Barber-Zucker, Shiran; Uebe, René; Davidov, Geula; Navon, Yotam; Sherf, Dror; Chill, Jordan H.; Kass, Itamar; Bitton, Ronit; Schüler, Dirk; Zarivach, Raz

    2016-01-01

    Cation diffusion facilitators (CDF) are highly conserved, metal ion efflux transporters that maintain divalent transition metal cation homeostasis. Most CDF proteins contain two domains, the cation transporting transmembrane domain and the regulatory cytoplasmic C-terminal domain (CTD). MamM is a magnetosome-associated CDF protein essential for the biomineralization of magnetic iron-oxide particles in magnetotactic bacteria. To investigate the structure-function relationship of CDF cytoplasmic domains, we characterized a MamM M250P mutation that is synonymous with the disease-related mutation L349P of the human CDF protein ZnT-10. Our results show that the M250P exchange in MamM causes severe structural changes in its CTD resulting in abnormal reduced function. Our in vivo, in vitro and in silico studies indicate that the CTD fold is critical for CDF proteins’ proper function and support the previously suggested role of the CDF cytoplasmic domain as a CDF regulatory element. Based on our results, we also suggest a mechanism for the effects of the ZnT-10 L349P mutation in human. PMID:27550551

  17. Spiroplasma eriocheiris Adhesin-Like Protein (ALP) Interacts with Epidermal Growth Factor (EGF) Domain Proteins to Facilitate Infection

    PubMed Central

    Hou, Libo; Liu, Yuhan; Gao, Qi; Xu, Xuechuan; Ning, Mingxiao; Bi, Jingxiu; Liu, Hui; Liu, Min; Gu, Wei; Wang, Wen; Meng, Qingguo

    2017-01-01

    Spiroplasma eriocheiris is a novel pathogen found in recent years, causing the tremor disease (TD) of Chinese mitten crab Eriocheir sinensis. Like Spiroplasma mirum, S. eriocheiris infects the newborn mouse (adult mice are not infected) and can cause cataract. Adhesion-related protein is an important protein involved in the interaction between pathogen and host. In this study, the Adhesin-like Protein (ALP) of S. eriocheiris was detected on its outer membrane by using immune electron microscopy, and was found to be involved in the bacterium's infection of mouse embryo fibroblasts (3T6-Swiss albino). Yeast two-hybrid analysis demonstrated that ALP interacts with a diverse group of mouse proteins. The interactions between recombinant partial fibulin7 (FBLN7; including two epidermal growth factor [EGF] domains) and ALP were confirmed by Far-western blotting and colocalization. We synthetized the domains of FBLN7 [EGF domain: amino acids 136–172 and complement control protein (CCP) domain: 81–134 amino acids], and demonstrated that only EGF domain of FBLN7 can interact with ALP. Because the EGF domain has high degree of similarity to EGF, it can activate the downstream EGFR signaling pathway, in key site amino acids. The EGFR pathway in 3T6 cells was restrained after rALP stimulation resulting from competitive binding of ALP to EGF. The unborn mouse, newborn mouse, and the adult mouse with cataract have a small amount of expressed FBLN7; however, none was detected in the brain and very little expression was seen in the eye of normal adult mice. In short, ALP as a S. eriocheiris surface protein, is critical for infection and further supports the role of ALP in S. eriocheiris infection by competitive effection of the EGF/EGFR axis of the target cells. PMID:28184355

  18. Crystal structure of the BoNT/A2 receptor-binding domain in complex with the luminal domain of its neuronal receptor SV2C

    PubMed Central

    Benoit, Roger M.; Schärer, Martin A.; Wieser, Mara M.; Li, Xiaodan; Frey, Daniel; Kammerer, Richard A.

    2017-01-01

    A detailed molecular understanding of botulinum neurotoxin (BoNT)/host-cell-receptor interactions is fundamental both for developing strategies against botulism and for generating improved BoNT variants for medical applications. The X-ray crystal structure of the receptor-binding domain (HC) of BoNT/A1 in complex with the luminal domain (LD) of its neuronal receptor SV2C revealed only few specific side-chain – side-chain interactions that are important for binding. Notably, two BoNT/A1 residues, Arg 1156 and Arg 1294, that are crucial for the interaction with SV2, are not conserved among subtypes. Because it has been suggested that differential receptor binding of subtypes might explain their differences in biological activity, we determined the crystal structure of BoNT/A2-HC in complex with SV2C-LD. Although only few side-chain interactions are conserved between the two BoNT/A subtypes, the overall binding mode of subtypes A1 and A2 is virtually identical. In the BoNT/A2-HC – SV2C complex structure, a missing cation-π stacking is compensated for by an additional salt bridge and an anion-π stacking interaction, which explains why the binding of BoNT/A subtypes to SV2C tolerates variable side chains. These findings suggest that motif extensions and a shallow binding cleft in BoNT/A-HC contribute to binding specificity. PMID:28252640

  19. Structural specializations of A2, a force-sensing domain in the ultralarge vascular protein von Willebrand factor

    SciTech Connect

    Zhang, Qing; Zhou, Yan-Feng; Zhang, Cheng-Zhong; Zhang, Xiaohui; Lu, Chafen; Springer, Timothy A.; Harvard-Med

    2009-06-30

    The lengths of von Willebrand factor (VWF) concatamers correlate with hemostatic potency. After secretion in plasma, length is regulated by hydrodynamic shear force-dependent unfolding of the A2 domain, which is then cleaved by a specific protease. The 1.9-{angstrom} crystal structure of the A2 domain demonstrates evolutionary adaptations to this shear sensor function. Unique among VWF A (VWA) domains, A2 contains a loop in place of the {alpha}4 helix, and a cis-proline. The central {beta}4-strand is poorly packed, with multiple side-chain rotamers. The Tyr-Met cleavage site is buried in the {beta}4-strand in the central hydrophobic core, and the Tyr structurally links to the C-terminal {alpha}6-helix. The {alpha}6-helix ends in 2 Cys residues that are linked by an unusual vicinal disulfide bond that is buried in a hydrophobic pocket. These features may narrow the force range over which unfolding occurs and may also slow refolding. Von Willebrand disease mutations, which presumably lower the force at which A2 unfolds, are illuminated by the structure.

  20. Regulation of Notch1 signaling by the APP intracellular domain facilitates degradation of the Notch1 intracellular domain and RBP-Jk.

    PubMed

    Kim, Mi-Yeon; Mo, Jung-Soon; Ann, Eun-Jung; Yoon, Ji-Hye; Jung, Jane; Choi, Yun-Hee; Kim, Su-Man; Kim, Hwa-Young; Ahn, Ji-Seon; Kim, Hangun; Kim, Kwonseop; Hoe, Hyang-Sook; Park, Hee-Sae

    2011-06-01

    The Notch1 receptor is a crucial controller of cell fate decisions, and is also a key regulator of cell growth and differentiation in a variety of contexts. In this study, we have demonstrated that the APP intracellular domain (AICD) attenuates Notch1 signaling by accelerated degradation of the Notch1 intracellular domain (Notch1-IC) and RBP-Jk, through different degradation pathways. AICD suppresses Notch1 transcriptional activity by the dissociation of the Notch1-IC-RBP-Jk complex after processing by γ-secretase. Notch1-IC is capable of forming a trimeric complex with Fbw7 and AICD, and AICD enhances the protein degradation of Notch1-IC through an Fbw7-dependent proteasomal pathway. AICD downregulates the levels of RBP-Jk protein through the lysosomal pathway. AICD-mediated degradation is involved in the preferential degradation of non-phosphorylated RBP-Jk. Collectively, our results demonstrate that AICD functions as a negative regulator in Notch1 signaling through the promotion of Notch1-IC and RBP-Jk protein degradation.

  1. Protein export by the mycobacterial SecA2 system is determined by the preprotein mature domain.

    PubMed

    Feltcher, Meghan E; Gibbons, Henry S; Ligon, Lauren S; Braunstein, Miriam

    2013-02-01

    At the core of the bacterial general secretion (Sec) pathway is the SecA ATPase, which powers translocation of unfolded preproteins containing Sec signal sequences through the SecYEG membrane channel. Mycobacteria have two nonredundant SecA homologs: SecA1 and SecA2. While the essential SecA1 handles "housekeeping" export, the nonessential SecA2 exports a subset of proteins and is required for Mycobacterium tuberculosis virulence. Currently, it is not understood how SecA2 contributes to Sec export in mycobacteria. In this study, we focused on identifying the features of two SecA2 substrates that target them to SecA2 for export, the Ms1704 and Ms1712 lipoproteins of the model organism Mycobacterium smegmatis. We found that the mature domains of Ms1704 and Ms1712, not the N-terminal signal sequences, confer SecA2-dependent export. We also demonstrated that the lipid modification and the extreme N terminus of the mature protein do not impart the requirement for SecA2 in export. We further showed that the Ms1704 mature domain can be efficiently exported by the twin-arginine translocation (Tat) pathway. Because the Tat system exports only folded proteins, this result implies that SecA2 substrates can fold in the cytoplasm and suggests a putative role of SecA2 in enabling export of such proteins. Thus, the mycobacterial SecA2 system may represent another way that bacteria solve the problem of exporting proteins that can fold in the cytoplasm.

  2. Insights into the Packing Switching of the EphA2 Transmembrane Domain by Molecular Dynamic Simulations.

    PubMed

    Sun, Fude; Xu, Lida; Chen, Peng; Wei, Peng; Qu, Jing; Chen, Jialin; Luo, Shi-Zhong

    2015-06-25

    Receptor tyrosine kinases play an important role in mediating cell migration and adhesion associated with various biology processes. With a single-span transmembrane domain (TMD), the activities of the receptors are regulated by the definite packing configurations of the TMDs. For the EphA2 receptor, increasing studies have been conducted to investigate the packing domains that induce its switching TMD dimerization. However, the inherent transformation mechanisms including the interrelations among the involved packing domains remain unclear. Herein, we applied multiple simulation methods to explore the underlying packing mechanisms within the EphA2 TMD dimer. Our results demonstrated that the G(540)xxxG(544) contributed to the formation of the right-handed configuration while the heptad repeat L(535)xxxG(539)xxA(542)xxxV(546)xxL(549)xxxG(553) motif together with the FFxH(559) region mediated the parallel mode. Furthermore, the FF(557) residues packing mutually as rigid riveting structures were found comparable to the heptad repeat motif in maintaining the parallel configuration. In addition, the H(559) residue associated definitely with the lower bilayer leaflet, which was proved to stabilize the parallel mode significantly. The simulations provide a full range of insights into the essential packing motifs or residues involved in the switching TMD dimer configurations, which can enrich our comprehension toward the EphA2 receptor.

  3. Nonconserved Residues Ala287 and Ser290 of the Cryptosporidium hominis Thymidylate Synthase Domain Facilitate Its Rapid Rate of Catalysis

    SciTech Connect

    Doan,L.; Martucci, W.; Vargo, M.; Atreya, C.; Anderson, K.

    2007-01-01

    Cryptosporidium hominis TS-DHFR exhibits an unusually high rate of catalysis at the TS domain, at least 10-fold greater than those of other TS enzymes. Using site-directed mutagenesis, we have mutated residues Ala287 and Ser290 in the folate-binding helix to phenylalanine and glycine, respectively, the corresponding residues in human and most other TS enzymes. Our results show that the mutant A287F, the mutant S290G, and the double mutant all have reduced affinities for methylene tetrahydrofolate and reduced rates of reaction at the TS domain. Interestingly, the S290G mutant enzyme had the lowest TS activity, with a catalytic efficiency {approx}200-fold lower than that of the wild type (WT). The rate of conformational change of the S290G mutant is {approx}80 times slower than that of WT, resulting in a change in the rate-limiting step from hydride transfer to covalent ternary complex formation. We have determined the crystal structure of ligand-bound S290G mutant enzyme, which shows that the primary effect of the mutation is an increase in the distance between the TS ligands. The kinetic and crystal structure data presented here provide the first evidence explaining the unusually fast TS rate in C. hominis.

  4. The S100A10 Subunit of the Annexin A2 Heterotetramer Facilitates L2-Mediated Human Papillomavirus Infection

    PubMed Central

    Woodham, Andrew W.; Da Silva, Diane M.; Skeate, Joseph G.; Raff, Adam B.; Ambroso, Mark R.; Brand, Heike E.; Isas, J. Mario; Langen, Ralf; Kast, W. Martin

    2012-01-01

    Mucosotropic, high-risk human papillomaviruses (HPV) are sexually transmitted viruses that are causally associated with the development of cervical cancer. The most common high-risk genotype, HPV16, is an obligatory intracellular virus that must gain entry into host epithelial cells and deliver its double stranded DNA to the nucleus. HPV capsid proteins play a vital role in these steps. Despite the critical nature of these capsid protein-host cell interactions, the precise cellular components necessary for HPV16 infection of epithelial cells remains unknown. Several neutralizing epitopes have been identified for the HPV16 L2 minor capsid protein that can inhibit infection after initial attachment of the virus to the cell surface, which suggests an L2-specific secondary receptor or cofactor is required for infection, but so far no specific L2-receptor has been identified. Here, we demonstrate that the annexin A2 heterotetramer (A2t) contributes to HPV16 infection and co-immunoprecipitates with HPV16 particles on the surface of epithelial cells in an L2-dependent manner. Inhibiting A2t with an endogenous annexin A2 ligand, secretory leukocyte protease inhibitor (SLPI), or with an annexin A2 antibody significantly reduces HPV16 infection. With electron paramagnetic resonance, we demonstrate that a previously identified neutralizing epitope of L2 (aa 108–120) specifically interacts with the S100A10 subunit of A2t. Additionally, mutation of this L2 region significantly reduces binding to A2t and HPV16 pseudovirus infection. Furthermore, downregulation of A2t with shRNA significantly decreases capsid internalization and infection by HPV16. Taken together, these findings indicate that A2t contributes to HPV16 internalization and infection of epithelial cells and this interaction is dependent on the presence of the L2 minor capsid protein. PMID:22927980

  5. Structures of Ca(V) Ca**2+/CaM-IQ Domain Complexes Reveal Binding Modes That Underlie Calcium-Dependent Inactivation And Facilitation

    SciTech Connect

    Kim, E.Y.; Rumpf, C.H.; Fujiwara, Y.; Cooley, E.S.; Petegem, F.Van; Minor, D.L., Jr.

    2009-05-20

    Calcium influx drives two opposing voltage-activated calcium channel (Ca{sub V}) self-modulatory processes: calcium-dependent inactivation (CDI) and calcium-dependent facilitation (CDF). Specific Ca{sup 2+}/calmodulin (Ca{sup 2+}/CaM) lobes produce CDI and CDF through interactions with the Ca{sub V}{alpha}{sub 1} subunit IQ domain. Curiously, Ca{sup 2+}/CaM lobe modulation polarity appears inverted between Ca{sub V}1s and Ca{sub V}2s. Here, we present crystal structures of Ca{sub V}2.1, Ca{sub V}2.2, and Ca{sub V}2.3 Ca{sup 2+}/CaM-IQ domain complexes. All display binding orientations opposite to Ca{sub V}1.2 with a physical reversal of the CaM lobe positions relative to the IQ {alpha}-helix. Titration calorimetry reveals lobe competition for a high-affinity site common to Ca{sub V}1 and Ca{sub V}2 IQ domains that is occupied by the CDI lobe in the structures. Electrophysiological experiments demonstrate that the N-terminal Ca{sub V}2 Ca{sup 2+}/C-lobe anchors affect CDF. Together, the data unveil the remarkable structural plasticity at the heart of Ca{sub V} feedback modulation and indicate that Ca{sub V}1 and Ca{sub V}2 IQ domains bear a dedicated CDF site that exchanges Ca{sup 2+}/CaM lobe occupants.

  6. Serotonin facilitates peripheral pain sensitivity in a manner that depends on the nonproton ligand sensing domain of ASIC3 channel.

    PubMed

    Wang, Xiang; Li, Wei-Guang; Yu, Ye; Xiao, Xian; Cheng, Jin; Zeng, Wei-Zheng; Peng, Zhong; Xi Zhu, Michael; Xu, Tian-Le

    2013-03-06

    Tissue acidosis and inflammatory mediators play critical roles in inflammatory pain. Extracellular acidosis activates acid-sensing ion channels (ASICs), which have emerged as key sensors for extracellular protons in the central and peripheral nervous systems and play key roles in pain sensation and transmission. Additionally, inflammatory mediators, such as serotonin (5-HT), are known to enhance pain sensation. However, functional interactions among protons, inflammatory mediators, and ASICs in pain sensation are poorly understood. In the present study, we show that 5-HT, a classical pro-inflammatory mediator, specifically enhances the proton-evoked sustained, but not transient, currents mediated by homomeric ASIC3 channels and heteromeric ASIC3/1a and ASIC3/1b channels. Unexpectedly, the effect of 5-HT on ASIC3 channels does not involve activation of 5-HT receptors, but is mediated via a functional interaction between 5-HT and ASIC3 channels. We further show that the effect of 5-HT on ASIC3 channels depends on the newly identified nonproton ligand sensing domain. Finally, coapplication of 5-HT and acid significantly increased pain-related behaviors as assayed by the paw-licking test in mice, which was largely attenuated in ASIC3 knock-out mice, and inhibited by the nonselective ASIC inhibitor amiloride. Together, these data identify ASIC3 channels as an unexpected molecular target for acute actions of 5-HT in inflammatory pain sensation and reveal an important role of ASIC3 channels in regulating inflammatory pain via coincident detection of extracellular protons and inflammatory mediators.

  7. The Functions of the A1A2A3 Domains in Von Willebrand Factor Include Multimerin 1 Binding

    PubMed Central

    Parker, D’Andra N.; Tasneem, Subia; Farndale, Richard W.; Bihan, Dominique; Sadler, J. Evan; Sebastian, Silvie; De Groot, Philip G.

    2016-01-01

    Summary Multimerin 1 (MMRN1) is a massive, homopolymeric protein that is stored in platelets and endothelial cells for activation-induced release. In vitro, MMRN1 binds to the outer surfaces of activated platelets and endothelial cells, the extracellular matrix (including collagen) and von Willebrand factor (VWF) to support platelet adhesive functions. VWF associates with MMRN1 at high shear, not static conditions, suggesting that shear exposes cryptic sites within VWF that support MMRN1 binding. Modified ELISA and surface plasmon resonance were used to study the structural features of VWF that support MMRN1 binding, and determine the affinities for VWF-MMRN1 binding. High shear microfluidic platelet adhesion assays determined the functional consequences for VWF-MMRN1 binding. VWF binding to MMRN1 was enhanced by shear exposure and ristocetin, and required VWF A1A2A3 region, specifically the A1 and A3 domains. VWF A1A2A3 bound to MMRN1 with a physiologically relevant binding affinity (KD: 2.0 ± 0.4 nM), whereas the individual VWF A1 (KD: 39.3 ± 7.7 nM) and A3 domains (KD: 229 ± 114 nM) bound to MMRN1 with lower affinities. VWF A1A2A3 was also sufficient to support the adhesion of resting platelets to MMRN1 at high shear, by a mechanism dependent on VWF-GPIbα binding. Our study provides new information on the molecular basis of MMRN1 binding to VWF, and its role in supporting platelet adhesion at high shear. We propose that at sites of vessel injury, MMRN1 that is released following activation of platelets and endothelial cells, binds to VWF A1A2A3 region to support platelet adhesion at arterial shear rates. PMID:27052467

  8. ApCPEB4, a non-prion domain containing homolog of ApCPEB, is involved in the initiation of long-term facilitation.

    PubMed

    Lee, Seung-Hee; Shim, Jaehoon; Cheong, Ye-Hwang; Choi, Sun-Lim; Jun, Yong-Woo; Lee, Sue-Hyun; Chae, Yeon-Su; Han, Jin-Hee; Lee, Yong-Seok; Lee, Jin-A; Lim, Chae-Seok; Si, Kausik; Kassabov, Stefan; Antonov, Igor; Kandel, Eric R; Kaang, Bong-Kiun; Jang, Deok-Jin

    2016-10-22

    Two pharmacologically distinct types of local protein synthesis are required for synapse- specific long-term synaptic facilitation (LTF) in Aplysia: one for initiation and the other for maintenance. ApCPEB, a rapamycin sensitive prion-like molecule regulates a form of local protein synthesis that is specifically required for the maintenance of the LTF. However, the molecular component of the local protein synthesis that is required for the initiation of LTF and that is sensitive to emetine is not known. Here, we identify a homolog of ApCPEB responsible for the initiation of LTF. ApCPEB4 which we have named after its mammalian CPEB4-like homolog lacks a prion-like domain, is responsive to 5-hydroxytryptamine, and is translated (but not transcribed) in an emetine-sensitive, rapamycin-insensitive, and PKA-dependent manner. The ApCPEB4 binds to different target RNAs than does ApCPEB. Knock-down of ApCPEB4 blocked the induction of LTF, whereas overexpression of ApCPEB4 reduces the threshold of the formation of LTF. Thus, our findings suggest that the two different forms of CPEBs play distinct roles in LTF; ApCPEB is required for maintenance of LTF, whereas the ApCPEB4, which lacks a prion-like domain, is required for the initiation of LTF.

  9. Calmodulin and calcium interplay in the modulation of TRPC5 channel activity. Identification of a novel C-terminal domain for calcium/calmodulin-mediated facilitation.

    PubMed

    Ordaz, Benito; Tang, Jisen; Xiao, Rui; Salgado, Alfonso; Sampieri, Alicia; Zhu, Michael X; Vaca, Luis

    2005-09-02

    TRPC5 forms Ca2+-permeable nonselective cation channels important for neurite outgrowth and growth cone morphology of hippocampal neurons. Here we studied the activation of mouse TRPC5 expressed in Chinese hamster ovary and human embryonic kidney 293 cells by agonist stimulation of several receptors that couple to the phosphoinositide signaling cascade and the role of calmodulin (CaM) on the activation. We showed that exogenous application of 10 microM CaM through patch pipette accelerated the agonist-induced channel activation by 2.8-fold, with the time constant for half-activation reduced from 4.25 +/- 0.4 to 1.56 +/- 0.85 min. We identified a novel CaM-binding site located at the C terminus of TRPC5, 95 amino acids downstream from the previously determined common CaM/IP3R-binding (CIRB) domain for all TRPC proteins. Deletion of the novel CaM-binding site attenuated the acceleration in channel activation induced by CaM. However, disruption of the CIRB domain from TRPC5 rendered the channel irresponsive to agonist stimulation without affecting the cell surface expression of the channel protein. Furthermore, we showed that high (>5 microM) intracellular free Ca2+ inhibited the current density without affecting the time course of TRPC5 activation by receptor agonists. These results demonstrated that intracellular Ca2+ has dual and opposite effects on the activation of TRPC5. The novel CaM-binding site is important for the Ca2+/CaM-mediated facilitation, whereas the CIRB domain is critical for the overall response of receptor-induced TRPC5 channel activation.

  10. The Kringle-like Domain Facilitates Post-endoplasmic Reticulum Changes to Premelanosome Protein (PMEL) Oligomerization and Disulfide Bond Configuration and Promotes Amyloid Formation*

    PubMed Central

    Ho, Tina; Watt, Brenda; Spruce, Lynn A.; Seeholzer, Steven H.; Marks, Michael S.

    2016-01-01

    The formation of functional amyloid must be carefully regulated to prevent the accumulation of potentially toxic products. Premelanosome protein (PMEL) forms non-toxic functional amyloid fibrils that assemble into sheets upon which melanins ultimately are deposited within the melanosomes of pigment cells. PMEL is synthesized in the endoplasmic reticulum but forms amyloid only within post-Golgi melanosome precursors; thus, PMEL must traverse the secretory pathway in a non-amyloid form. Here, we identified two pre-amyloid PMEL intermediates that likely regulate the timing of fibril formation. Analyses by non-reducing SDS-PAGE, size exclusion chromatography, and sedimentation velocity revealed two native high Mr disulfide-bonded species that contain Golgi-modified forms of PMEL. These species correspond to disulfide bond-containing dimeric and monomeric PMEL isoforms that contain no other proteins as judged by two-dimensional PAGE of metabolically labeled/immunoprecipitated PMEL and by mass spectrometry of affinity-purified complexes. Metabolic pulse-chase analyses, small molecule inhibitor treatments, and evaluation of site-directed mutants suggest that the PMEL dimer forms around the time of endoplasmic reticulum exit and is resolved by disulfide bond rearrangement into a monomeric form within the late Golgi or a post-Golgi compartment. Mutagenesis of individual cysteine residues within the non-amyloid cysteine-rich Kringle-like domain stabilizes the disulfide-bonded dimer and impairs fibril formation as determined by electron microscopy. Our data show that the Kringle-like domain facilitates the resolution of disulfide-bonded PMEL dimers and promotes PMEL functional amyloid formation, thereby suggesting that PMEL dimers must be resolved to monomers to generate functional amyloid fibrils. PMID:26694611

  11. Cloning and Characterization of a 2-Cys Peroxiredoxin in the Pine Wood Nematode, Bursaphelenchus xylophilus, a Putative Genetic Factor Facilitating the Infestation

    PubMed Central

    Li, Zhen; Liu, Xiaoxia; Chu, Yanna; Wang, Yan; Zhang, Qingwen; Zhou, Xuguo

    2011-01-01

    The pine wood nematode, Bursaphelenchus xylophilus, is an invasive plant parasitic nematode and a worldwide quarantine pest. An indigenous species in North America and the causal agent of pine wilt disease, B. xylophilus has devastated pine production in Southeastern Asia including Japan, China, and Korea since its initial introduction in the early 1900s. The reactive oxygen species (ROS) is the first line of defense utilized by host plants against parasites, while nematodes, counteractively, employ antioxidants to facilitate their infection. Peroxiredoxins (Prxs) are a large class of antioxidants recently found in a wide variety of organisms. In this report, a gene encoding a novel 2-cysteine peroxiredoxin protein in B. xylophilus was cloned and characterized. The 2-cysteine peroxiredoxin in B. xylophilus (herein refers to as “BxPrx”) is highly conserved in comparison to 2-cysteine peroxiredoxins (Prx2s) in other nematodes, which have two conserved cysteine amino acids (Cp and Cr), a threonine-cysteine-arginine catalytic triad, and two signature motifs (GGLG and YF) sensitive to hydrogen peroxide. In silico assembly of BxPrx tertiary structure reveals the spatial configuration of these conserved domains and the simulated BxPrx 3-dimensional structure is congruent with its presumed redox functions. Although no signal peptide was identified, BxPrx was abundantly expressed and secreted under the B. xylophilus cuticle. Upon further analysis of this leader-less peptide, a single transmembrane α-helix composed of 23 consecutive hydrophobic amino acids was found in the primary structure of BxPrx. This transmembrane region and/or readily available ATP binding cassette transporters may facilitate the transport of non-classical BxPrx across the cell membrane. Recombinant BxPrx showed peroxidase activity in vitro reducing hydrogen peroxide using glutathione as the electron donor. The combined results from gene discovery, protein expression and distribution profiling

  12. Differential domain evolution and complex RNA processing in a family of paralogous EPB41 (protein 4.1) genes facilitates expression of diverse tissue-specific isoforms

    SciTech Connect

    Parra, Marilyn; Gee, Sherry; Chan, Nadine; Ryaboy, Dmitriy; Dubchak, Inna; Narla, Mohandas; Gascard, Philippe D.; Conboy, John G.

    2004-07-15

    The EPB41 (protein 4.1) genes epitomize the resourcefulness of the mammalian genome to encode a complex proteome from a small number of genes. By utilizing alternative transcriptional promoters and tissue-specific alternative pre-mRNA splicing, EPB41, EPB41L2, EPB41L3, and EPB41L1 encode a diverse array of structural adapter proteins. Comparative genomic and transcript analysis of these 140kb-240kb genes indicates several unusual features: differential evolution of highly conserved exons encoding known functional domains, interspersed with unique exons whose size and sequence variations contribute substantially to intergenic diversity: alternative first exons, most of which map far upstream of the coding regions; and complex tissue-specific alternative pre-mRNA splicing that facilitates synthesis of functionally different complements of 4.1 proteins in various cells. Understanding the splicing regulatory networks that control protein 4.1 expression will be critical to a full appreciation of the many roles of 4.1 proteins in normal cell biology and their proposed roles in human cancer.

  13. Potentiation by tonic A2a-adenosine receptor activation of CGRP-facilitated [3H]-ACh release from rat motor nerve endings.

    PubMed Central

    Correia-de-Sá, P.; Ribeiro, J. A.

    1994-01-01

    1. The effect of calcitonin gene-related peptide (CGRP) on [3H]-acetylcholine ([3H]-ACh) release from motor nerve endings and its interaction with presynaptic facilitatory A2a-adenosine and nicotinic acetylcholine receptors was studied on rat phrenic nerve-hemidiaphragm preparations loaded with [3H]-choline. 2. CGRP (100-400 nM) increased electrically evoked [3H]-ACh release from phrenic nerve endings in a concentration-dependent manner. 3. The magnitude of CGRP excitation increased with the increase of the stimulation pulse duration from 40 microseconds to 1 ms, keeping the frequency, the amplitude and the train length constants. With 1 ms pulses, the evoked [3H]-ACh release was more intense than with 40 microseconds pulse duration. 4. Both the nicotinic acetylcholine receptor agonist, 1,1-dimethyl-4-phenylpiperazinium, and the A2a adenosine receptor agonist, CGS 21680C, increased evoked [3H]-ACh release, but only CGS 21680C potentiated the facilitatory effect of CGRP. This potentiation was prevented by the A2a adenosine receptor antagonist, PD 115,199. 5. Adenosine deaminase prevented the excitatory effect of CGRP (400 nM) on [3H]-ACh release. This effect was reversed by the non-hydrolysable A2a-adenosine receptor agonist, CGS 21680C. 6. The nicotinic antagonist, tubocurarine, did not significantly change, whereas the A2-adenosine receptor antagonist, PD 115,199, blocked the CGRP facilitation. The A1-adenosine receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine, potentiated the CGRP excitatory effect. 7. The results suggest that the facilitatory effect of CGRP on evoked [3H]-ACh release from rat phrenic motor nerve endings depends on the presence of endogenous adenosine which tonically activates A2a-adenosine receptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8004402

  14. Structural and binding properties of the PASTA domain of PonA2, a key penicillin binding protein from Mycobacterium tuberculosis.

    PubMed

    Calvanese, Luisa; Falcigno, Lucia; Maglione, Cira; Marasco, Daniela; Ruggiero, Alessia; Squeglia, Flavia; Berisio, Rita; D'Auria, Gabriella

    2014-07-01

    PonA2 is one of the two class A penicillin binding proteins of Mycobacterium tuberculosis, the etiologic agent of tuberculosis. It plays a complex role in mycobacterial physiology and is spotted as a promising target for inhibitors. PonA2 is involved in adaptation of M. tuberculosis to dormancy, an ability which has been attributed to the presence in its sequence of a C-terminal PASTA domain. Since PASTA modules are typically considered as β-lactam antibiotic binding domains, we determined the solution structure of the PASTA domain from PonA2 and analyzed its binding properties versus a plethora of potential binders, including the β-lactam antibiotics, two typical muropeptide mimics, and polymeric peptidoglycan. We show that, despite a high structural similarity with other PASTA domains, the PASTA domain of PonA2 displays different binding properties, as it is not able to bind muropeptides, or β-lactams, or polymeric peptidoglycan. These results indicate that the role of PASTA domains cannot be generalized, as their specific binding properties strongly depend on surface residues, which are widely variable.

  15. Identification of the Major Ubiquitin-binding Domain of the Pseudomonas aeruginosa ExoU A2 Phospholipase*

    PubMed Central

    Anderson, David M.; Feix, Jimmy B.; Monroe, Andrew L.; Peterson, Francis C.; Volkman, Brian F.; Haas, Arthur L.; Frank, Dara W.

    2013-01-01

    Numerous Gram-negative bacterial pathogens use type III secretion systems to deliver effector molecules into the cytoplasm of a host cell. Many of these effectors have evolved to manipulate the host ubiquitin system to alter host cell physiology or the location, stability, or function of the effector itself. ExoU is a potent A2 phospholipase used by Pseudomonas aeruginosa to destroy membranes of infected cells. The enzyme is held in an inactive state inside of the bacterium due to the absence of a required eukaryotic activator, which was recently identified as ubiquitin. This study sought to identify the region of ExoU required to mediate this interaction and determine the properties of ubiquitin important for binding, ExoU activation, or both. Biochemical and biophysical approaches were used to map the ubiquitin-binding domain to a C-terminal four-helix bundle of ExoU. The hydrophobic patch of ubiquitin is required for full binding affinity and activation. Binding and activation were uncoupled by introducing an L8R substitution in ubiquitin. Purified L8R demonstrated a parental binding phenotype to ExoU but did not activate the phospholipase in vitro. Utilizing these new biochemical data and intermolecular distance measurements by double electron-electron resonance, we propose a model for an ExoU-monoubiquitin complex. PMID:23908356

  16. Influenza A virus virulence depends on two amino acids in the N-terminal domain of its NS1 protein facilitating inhibition of PKR.

    PubMed

    Schierhorn, Kristina L; Jolmes, Fabian; Bespalowa, Julia; Saenger, Sandra; Peteranderl, Christin; Dzieciolowski, Julia; Budt, Matthias; Pleschka, Stephan; Herrmann, Andreas; Herold, Susanne; Wolff, Thorsten

    2017-03-01

    The RNA-dependent protein kinase (PKR) has broad antiviral activity inducing translational shut-down of viral and cellular genes and is therefore targeted by various viral proteins to facilitate pathogen propagation. The pleiotropic NS1 protein of influenza A virus acts as silencer of PKR activation and ascertains high level viral replication and virulence. However, the exact way of this inhibition remains controversial. To elucidate the structural requirements within the NS1 protein for PKR inhibition, we generated a set of mutant viruses identifying highly conserved arginine residues 35 and 46 within the NS1 N-terminus as being most critical not only for binding to and blocking activation of PKR, but also for efficient virus propagation. Biochemical and FRET-based interaction studies showed that mutation of each of R35 or R46 allowed formation of NS1 dimers, but eliminated any detectable binding to PKR as well as to dsRNA. Using in vitro and in vivo approaches of phenotypic restoration we demonstrate the essential role of the NS1 N-terminus for blocking PKR. The strong attenuation conferred by NS1 mutations R35A or R46A was substantially alleviated by stable knock-down of PKR in human cells. Intriguingly, both NS1 mutant viruses did not trigger any signs of disease in PKR(+/+) mice, but replicated to high titers in lungs of PKR(-/-) mice and caused lethal infections. These data not only establish the NS1 N-terminus as highly critical for neutralization of PKR's antiviral activity, but also identify this blockade as an indispensable contribution of NS1 to the viral life cycle.IMPORTANCE Influenza A virus inhibits activation of the RNA-dependent protein kinase PKR by means of its non-structural NS1 protein, but the underlying mode of inhibition is debated. Using mutational analysis, we identify arginine residues 35 and 46 within the N-terminal NS1 domain as highly critical for binding to and functional silencing of PKR. In addition, our data show that this is a

  17. RapA2 Is a Calcium-binding Lectin Composed of Two Highly Conserved Cadherin-like Domains That Specifically Recognize Rhizobium leguminosarum Acidic Exopolysaccharides*

    PubMed Central

    Abdian, Patricia L.; Caramelo, Julio J.; Ausmees, Nora; Zorreguieta, Angeles

    2013-01-01

    In silico analyses have revealed a conserved protein domain (CHDL) widely present in bacteria that has significant structural similarity to eukaryotic cadherins. A CHDL domain was shown to be present in RapA, a protein that is involved in autoaggregation of Rhizobium cells, biofilm formation, and adhesion to plant roots as shown by us and others. Structural similarity to cadherins suggested calcium-dependent oligomerization of CHDL domains as a mechanistic basis for RapA action. Here we show by circular dichroism spectroscopy, light scattering, isothermal titration calorimetry, and other methods that RapA2 from Rhizobium leguminosarum indeed exhibits a cadherin-like β-sheet conformation and that its proper folding and stability are dependent on the binding of one calcium ion per protein molecule. By further in silico analysis we also reveal that RapA2 consists of two CHDL domains and expand the range of CHDL-containing proteins in bacteria and archaea. However, light scattering assays at various concentrations of added calcium revealed that RapA2 formed neither homo-oligomers nor hetero-oligomers with RapB (a distinct CHDL protein), indicating that RapA2 does not mediate cellular interactions through a cadherin-like mechanism. Instead, we demonstrate that RapA2 interacts specifically with the acidic exopolysaccharides (EPSs) produced by R. leguminosarum in a calcium-dependent manner, sustaining a role of these proteins in the development of the biofilm matrix made of EPS. Because EPS binding by RapA2 can only be attributed to its two CHDL domains, we propose that RapA2 is a calcium-dependent lectin and that CHDL domains in various bacterial and archaeal proteins confer carbohydrate binding activity to these proteins. PMID:23235153

  18. Tetanic depression is overcome by tonic adenosine A2A receptor facilitation of L-type Ca2+ influx into rat motor nerve terminals

    PubMed Central

    Oliveira, Laura; Timóteo, M Alexandrina; Correia-de-Sá, Paulo

    2004-01-01

    Motor nerve terminals possess multiple voltage-sensitive calcium channels operating acetylcholine (ACh) release. In this study, we investigated whether facilitation of neuromuscular transmission by adenosine generated during neuronal firing was operated by Ca2+ influx via ‘prevalent’ P-type or via the recruitment of ‘silent’ L-type channels. The release of [3H]ACh from rat phrenic nerve endings decreased upon increasing the stimulation frequency of the trains (750 pulses) from 5 Hz (83 ± 4 × 103 disintegrations per minute per gram (d.p.m. g−1); n = 11) to 50 Hz (30 ± 3 × 103 d.p.m. g−1; n = 5). The P-type Ca2+ channel blocker, ω-agatoxin IVA (100 nm) reduced (by 40 ± 10%; n = 6) the release of [3H]ACh evoked by 50-Hz trains, while nifedipine (1 μm, an L-type blocker) was inactive. Tetanic depression was overcome (88 ± 6 × 103 d.p.m. g−1; n = 12) by stimulating the phrenic nerve with 50-Hz bursts (five bursts of 150 pulses, 20 s interburst interval). In these conditions, ω-agatoxin IVA (100 nm) failed to affect transmitter release, but nifedipine (1 μm) decreased [3H]ACh release by 21 ± 7% (n = 4). Inactivation of endogenous adenosine with adenosine deaminase (ADA, 0.5 U ml−1) reduced (by 54 ± 8%, n = 5) the release of [3H]ACh evoked with 50-Hz bursts. This effect was opposite to the excitatory actions of adenosine (0.5 mm), S-(p-nitrobenzyl)-6-thioinosine (5 μm, an adenosine uptake blocker) and CGS 21680C (3 nm, a selective A2A receptor agonist); as the A1 receptor agonist R-N6-phenylisopropyl adenosine (R-PIA, 300 nm) failed to affect the release of [3H]ACh, the results indicate that adenosine generated during 50-Hz bursts exerts an A2A-receptor-mediated tonus. The effects of ADA (0.5 U ml−1) and CGS 21680C (3 nm) were prevented by nifedipine (1 μm). Blocking tonic A2A receptor activation, with ADA (0.5 U ml−1) or 3,7-dimethyl-1-propargyl xanthine (10 μm, an A2A antagonist), recovered ω-agatoxin IVA (100 nm) inhibition and

  19. The N-terminal pleckstrin, coiled-coil, and IQ domains of the exchange factor Ras-GRF act cooperatively to facilitate activation by calcium.

    PubMed

    Buchsbaum, R; Telliez, J B; Goonesekera, S; Feig, L A

    1996-09-01

    We have recently shown that the neuronal exchange factor p140 Ras-GRF becomes activated in vivo in response to elevated calcium levels [C. L. Farnsworth, N. W. Freshney, L. B. Rosen, A. Ghosh, M. E. Greenberg, and L. A. Feig, Nature (London) 376:524-527, 1995]. Activation is mediated by calcium-induced calmodulin binding to an IQ domain near the N terminus of Ras-GRF. Here we show that the adjacent N-terminal pleckstrin homology (PH), coiled-coil, and IQ domains function cooperatively to allow Ras-GRF activation. Deletion of the N-terminal PH domain redistributes a large percentage of Ras-GRF from the particulate to the cytosolic fraction of cells and renders the protein insensitive to calcium stimulation. A similar cellular distribution and biological activity are observed when only the core catalytic domain is expressed. Although the PH domain is necessary for particulate association of Ras-GRF, it is not sufficient for targeting the core catalytic domain to this cellular location. This requires the PH domain and the adjacent coiled-coil and IQ sequences. Remarkably, this form of Ras-GRF is constitutively activated. The PH and coiled-coil domains must also perform an additional function, since targeting to the particulate fraction of cells is not sufficient to allow Ras-GRF activation by calcium. A Ras-GRF mutant containing the PH domain from Ras-GTPase-activating protein in place of its own N-terminal PH domain localizes to the particulate fraction of cells but does not respond to calcium. Similar phenotypes are seen with mutant Ras-GRFs containing point mutations in either the PH or coiled-coil domain. These findings argue that the N-terminal PH, coiled-coil, and IQ domains of Ras-GRF function together to connect Ras-GRF to multiple components in the particulate fractions of cells that are required for responsiveness of the protein to calcium signaling.

  20. Missense mutations near the N-glycosylation site of the A2 domain lead to various intracellular trafficking defects in coagulation factor VIII

    PubMed Central

    Wei, Wei; Zheng, Chunlei; Zhu, Min; Zhu, Xiaofan; Yang, Renchi; Misra, Saurav; Zhang, Bin

    2017-01-01

    Missense mutation is the most common mutation type in hemophilia. However, the majority of missense mutations remain uncharacterized. Here we characterize how hemophilia mutations near the unused N-glycosylation site of the A2 domain (N582) of FVIII affect protein conformation and intracellular trafficking. N582 is located in the middle of a short 310-helical turn (D580-S584), in which most amino acids have multiple hemophilia mutations. All 14 missense mutations found in this 310-helix reduced secretion levels of the A2 domain and full-length FVIII. Secreted mutants have decreased activities relative to WT FVIII. Selected mutations also lead to partial glycosylation of N582, suggesting that rapid folding of local conformation prevents glycosylation of this site in wild-type FVIII. Protease sensitivity, stability and degradation of the A2 domain vary among mutants, and between non-glycosylated and glycosylated species of the same mutant. Most of the mutants interact with the ER chaperone BiP, while only mutants with aberrant glycosylation interact with calreticulin. Our results show that the short 310-helix from D580 to S584 is critical for proper biogenesis of the A2 domain and FVIII, and reveal a range of molecular mechanisms by which FVIII missense mutations lead to moderate to severe hemophilia A. PMID:28327546

  1. Annexin A2 reduces PCSK9 protein levels via a translational mechanism and interacts with the M1 and M2 domains of PCSK9.

    PubMed

    Ly, Kévin; Saavedra, Yascara Grisel Luna; Canuel, Maryssa; Routhier, Sophie; Desjardins, Roxane; Hamelin, Josée; Mayne, Janice; Lazure, Claude; Seidah, Nabil G; Day, Robert

    2014-06-20

    Annexin A2 (AnxA2) was reported to be an extracellular endogenous inhibitor of proprotein convertase subtilisin kexin type 9 (PCSK9) activity on cell-surface LDL receptor degradation. In this study, we investigated the effect of silencing the expression of AnxA2 and PCSK9 in HepG2 and Huh7 cells to better define the role of AnxA2 in PCSK9 regulation. AnxA2 knockdown in Huh7 cells significantly increased PCSK9 protein levels as opposed to AnxA2 knockdown in HepG2 cells. However, HepG2 cells overexpressing AnxA2 had lower levels of PCSK9 protein. Overall, our data revealed a plausible new role of AnxA2 in the reduction of PCSK9 protein levels via a translational mechanism. Moreover, the C-terminal Cys/His-rich domain of PCSK9 is crucial in the regulation of PCSK9 activity, and we demonstrated by far-Western blot assay that the M1 and M2 domains are necessary for the specific interaction of PCSK9's C-terminal Cys/His-rich domain and AnxA2. Finally, we produced and purified recombinant PCSK9 from humans and mice, which was characterized and used to perform 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate LDL cell-based assays on the stable knockdown HepG2 and Huh7 cells. We also demonstrated for the first time the equipotency of human and mouse PCSK9 R218S on human cells.

  2. Discovery of the cell-penetrating function of A2 domain derived from LTA subunit of Escherichia coli heat-labile enterotoxin.

    PubMed

    Liu, Di; Guo, Hua; Zheng, Wenyun; Zhang, Na; Wang, Tianwen; Wang, Ping; Ma, Xingyuan

    2016-06-01

    Heat-labile enterotoxin (LT) is a protein toxin produced by enterotoxigenic Escherichia coli (ETEC). As a bacterial toxin, LT holotoxin can enter intestinal epithelial cells and cause diarrhea. In addition, LT is also a powerful mucosal adjuvant capable of enhancing the strong immune responses to co-administered antigens. However, the LT immunological mechanism is still not clear in some aspects, especially with the respect to how the LTA subunit functions alone. Here, we discovered that the A2 domain of LTA could carry a fluorescent protein into cells, whose function is similar to a cell-penetrating peptide. The transmembrane-transporting ability of the A2 domain is non-specific in its cell-penetrating function, which was shown through testing with different cell types. Moreover, the LTA2 fusion protein penetrated a fluorescently labeled cell membrane that identified LTA2 internalization through membrane transport pathways, and showed it finally localized in the endoplasmic reticulum. Furthermore, low-temperature stress and pharmacological agent treatments showed that the LTA2 internalization route is a temperature-dependent process involving the clathrin-mediated endocytosis and the macropinocytosis pathways. These results could explain the internalization of the LTA subunit alone without the LTB pentamer, contributing to a better understanding of LTA working as a mucosal adjuvant; they also suggest that the A2 domain could be used as a novel transport vehicle for research and treatment of disease.

  3. Molecular mimicry of human tRNALys anti-codon domain by HIV-1 RNA genome facilitates tRNA primer annealing.

    PubMed

    Jones, Christopher P; Saadatmand, Jenan; Kleiman, Lawrence; Musier-Forsyth, Karin

    2013-02-01

    The primer for initiating reverse transcription in human immunodeficiency virus type 1 (HIV-1) is tRNA(Lys3). Host cell tRNA(Lys) is selectively packaged into HIV-1 through a specific interaction between the major tRNA(Lys)-binding protein, human lysyl-tRNA synthetase (hLysRS), and the viral proteins Gag and GagPol. Annealing of the tRNA primer onto the complementary primer-binding site (PBS) in viral RNA is mediated by the nucleocapsid domain of Gag. The mechanism by which tRNA(Lys3) is targeted to the PBS and released from hLysRS prior to annealing is unknown. Here, we show that hLysRS specifically binds to a tRNA anti-codon-like element (TLE) in the HIV-1 genome, which mimics the anti-codon loop of tRNA(Lys) and is located proximal to the PBS. Mutation of the U-rich sequence within the TLE attenuates binding of hLysRS in vitro and reduces the amount of annealed tRNA(Lys3) in virions. Thus, LysRS binds specifically to the TLE, which is part of a larger LysRS binding domain in the viral RNA that includes elements of the Psi packaging signal. Our results suggest that HIV-1 uses molecular mimicry of the anti-codon of tRNA(Lys) to increase the efficiency of tRNA(Lys3) annealing to viral RNA.

  4. A Novel Rrm3 Function in Restricting DNA Replication via an Orc5-Binding Domain Is Genetically Separable from Rrm3 Function as an ATPase/Helicase in Facilitating Fork Progression

    PubMed Central

    Syed, Salahuddin; Desler, Claus; Rasmussen, Lene J.; Schmidt, Kristina H.

    2016-01-01

    In response to replication stress cells activate the intra-S checkpoint, induce DNA repair pathways, increase nucleotide levels, and inhibit origin firing. Here, we report that Rrm3 associates with a subset of replication origins and controls DNA synthesis during replication stress. The N-terminal domain required for control of DNA synthesis maps to residues 186–212 that are also critical for binding Orc5 of the origin recognition complex. Deletion of this domain is lethal to cells lacking the replication checkpoint mediator Mrc1 and leads to mutations upon exposure to the replication stressor hydroxyurea. This novel Rrm3 function is independent of its established role as an ATPase/helicase in facilitating replication fork progression through polymerase blocking obstacles. Using quantitative mass spectrometry and genetic analyses, we find that the homologous recombination factor Rdh54 and Rad5-dependent error-free DNA damage bypass act as independent mechanisms on DNA lesions that arise when Rrm3 catalytic activity is disrupted whereas these mechanisms are dispensable for DNA damage tolerance when the replication function is disrupted, indicating that the DNA lesions generated by the loss of each Rrm3 function are distinct. Although both lesion types activate the DNA-damage checkpoint, we find that the resultant increase in nucleotide levels is not sufficient for continued DNA synthesis under replication stress. Together, our findings suggest a role of Rrm3, via its Orc5-binding domain, in restricting DNA synthesis that is genetically and physically separable from its established catalytic role in facilitating fork progression through replication blocks. PMID:27923055

  5. The Kaposi Sarcoma Herpesvirus Latency-associated Nuclear Antigen DNA Binding Domain Dorsal Positive Electrostatic Patch Facilitates DNA Replication and Episome Persistence.

    PubMed

    Li, Shijun; Tan, Min; Juillard, Franceline; Ponnusamy, Rajesh; Correia, Bruno; Simas, J Pedro; Carrondo, Maria A; McVey, Colin E; Kaye, Kenneth M

    2015-11-20

    Kaposi sarcoma-associated herpesvirus (KSHV) has a causative role in several human malignancies. KSHV latency-associated nuclear antigen (LANA) mediates persistence of viral episomes in latently infected cells. LANA mediates KSHV DNA replication and segregates episomes to progeny nuclei. The structure of the LANA DNA binding domain was recently solved, revealing a positive electrostatic patch opposite the DNA binding surface, which is the site of BET protein binding. Here we investigate the functional role of the positive patch in LANA-mediated episome persistence. As expected, LANA mutants with alanine or glutamate substitutions in the central, peripheral, or lateral portions of the positive patch maintained the ability to bind DNA by EMSA. However, all of the substitution mutants were deficient for LANA DNA replication and episome maintenance. Mutation of the peripheral region generated the largest deficiencies. Despite these deficiencies, all positive patch mutants concentrated to dots along mitotic chromosomes in cells containing episomes, similar to LANA. The central and peripheral mutants, but not the lateral mutants, were reduced for BET protein interaction as assessed by co-immunoprecipitation. However, defects in BET protein binding were independent of episome maintenance function. Overall, the reductions in episome maintenance closely correlated with DNA replication deficiencies, suggesting that the replication defects account for the reduced episome persistence. Therefore, the electrostatic patch exerts a key role in LANA-mediated DNA replication and episome persistence and may act through a host cell partner(s) other than a BET protein or by inducing specific structures or complexes.

  6. A conserved carboxy-terminal domain in the major tegument structural protein VP22 facilitates virion packaging of a chimeric protein during productive herpes simplex virus 1 infection

    SciTech Connect

    Schlegel, Elisabeth F.M.; Blaho, John A.

    2009-05-10

    Recombinant virus HSV-1(RF177) was previously generated to examine tegument protein VP22 function by inserting the GFP gene into the gene encoding VP22. During a detailed analysis of this virus, we discovered that RF177 produces a novel fusion protein between the last 15 amino acids of VP22 and GFP, termed GCT-VP22. Thus, the VP22 carboxy-terminal specific antibody 22-3 and two anti-GFP antibodies reacted with an approximately 28 kDa protein from RF177-infected Vero cells. GCT-VP22 was detected at 1 and 3 hpi. Examination of purified virions indicated that GCT-VP22 was incorporated into RF177 virus particles. These observations imply that at least a portion of the information required for virion targeting is located in this domain of VP22. Indirect immunofluorescence analyses showed that GCT-VP22 also localized to areas of marginalized chromatin during RF177 infection. These results indicate that the last fifteen amino acids of VP22 participate in virion targeting during HSV-1 infection.

  7. Hydroxylation of aspartic acid in domains homologous to the epidermal growth factor precursor is catalyzed by a 2-oxoglutarate-dependent dioxygenase.

    PubMed Central

    Stenflo, J; Holme, E; Lindstedt, S; Chandramouli, N; Huang, L H; Tam, J P; Merrifield, R B

    1989-01-01

    3-Hydroxyaspartic acid and 3-hydroxyasparagine are two rare amino acids that are present in domains homologous to the epidermal growth factor precursor in vitamin K-dependent plasma proteins as well as in proteins that do not require vitamin K for normal biosynthesis. They are formed by posttranslational hydroxylation of aspartic acid and asparagine, respectively. The first epidermal growth factor-like domain in factor IX (residues 45-87) was synthesized with aspartic acid in position 64, replacing 3-hydroxyaspartic acid. It was used as substrate in a hydroxylase assay with rat liver microsomes as the source of enzyme and reaction conditions that satisfy the requirements of 2-oxoglutarate-dependent dioxygenases. The synthetic peptide stimulated the 2-oxoglutarate decarboxylation in contrast to synthetic, modified epidermal growth factor (Met-21 and His-22 deleted and Glu-24 replaced by Asp) and synthetic peptides corresponding to residues 60-71 in human factor IX. This indicates that the hydroxylase is a 2-oxoglutarate-dependent dioxygenase with a selective substrate requirement. Images PMID:2492106

  8. Postsynaptic VAMP/Synaptobrevin Facilitates Differential Vesicle Trafficking of GluA1 and GluA2 AMPA Receptor Subunits

    PubMed Central

    Hussain, Suleman; Davanger, Svend

    2015-01-01

    Vertebrate organisms adapt to a continuously changing environment by regulating the strength of synaptic connections between brain cells. Excitatory synapses are believed to increase their strength by vesicular insertion of transmitter glutamate receptors into the postsynaptic plasma membrane. These vesicles, however, have never been demonstrated or characterized. For the first time, we show the presence of small vesicles in postsynaptic spines, often closely adjacent to the plasma membrane and PSD (postsynaptic density). We demonstrate that they harbor vesicle-associated membrane protein 2 (VAMP2/synaptobrevin-2) and glutamate receptor subunit 1 (GluA1). Disrupting VAMP2 by tetanus toxin treatment reduces the concentration of GluA1 in the postsynaptic plasma membrane. GluA1/VAMP2-containing vesicles, but not GluA2/VAMP2-vesicles, are concentrated in postsynaptic spines relative to dendrites. Our results indicate that small postsynaptic vesicles containing GluA1 are inserted directly into the spine plasma membrane through a VAMP2-dependent mechanism. PMID:26488171

  9. A2A adenosine-receptor-mediated facilitation of noradrenaline release in rat tail artery involves protein kinase C activation and betagamma subunits formed after alpha2-adrenoceptor activation.

    PubMed

    Fresco, Paula; Oliveira, Jorge M A; Kunc, Filip; Soares, Ana Sofia; Rocha-Pereira, Carolina; Gonçalves, Jorge; Diniz, Carmen

    2007-07-01

    This work aimed to investigate the molecular mechanisms involved in the interaction of alpha2-adrenoceptors and adenosine A2A-receptor-mediated facilitation of noradrenaline release in rat tail artery, namely the type of G-protein involved in this effect and the step or steps where the signalling cascades triggered by alpha2-adrenoceptors and A2A-receptors interact. The selective adenosine A2A-receptor agonist 2-p-(2-carboxy ethyl) phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS 21680; 100 nM) enhanced tritium overflow evoked by trains of 100 pulses at 5 Hz. This effect was abolished by the selective adenosine A2A-receptor antagonist 5-amino-7-(2-phenyl ethyl)-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo [1,5-c]pyrimidine (SCH 58261; 20 nM) and by yohimbine (1 microM). CGS 21680-mediated effects were also abolished by drugs that disrupted G(i/o)-protein coupling with receptors, PTX (2 microg/ml) or NEM (40 microM), by the anti-G(salpha) peptide (2 microg/ml) anti-G(betagamma) peptide (10 microg/ml) indicating coupling of A2A-receptors to G(salpha) and suggesting a crucial role for G(betagamma) subunits in the A(2A)-receptor-mediated enhancement of tritium overflow. Furthermore, phorbol 12-myristate 13-acetate (PMA; 1 microM) or forskolin (1 microM), direct activators of protein kinase C and of adenylyl cyclase, respectively, also enhanced tritium overflow. In addition, PMA-mediated effects were not observed in the presence of either yohimbine or PTX. Results indicate that facilitatory adenosine A2A-receptors couple to G(salpha) subunits which is essential, but not sufficient, for the release facilitation to occur, requiring the involvement of G(i/o)-protein coupling (it disappears after disruption of G(i/o)-protein coupling, PTX or NEM) and/or G(betagamma) subunits (anti-G(betagamma)). We propose a mechanism for the interaction in study suggesting group 2 AC isoforms as a plausible candidate for the interaction site, as these isoforms can integrate inputs from G

  10. Murine AKAP7 Has a 2′,5′-Phosphodiesterase Domain That Can Complement an Inactive Murine Coronavirus ns2 Gene

    PubMed Central

    Gusho, Elona; Zhang, Rong; Jha, Babal K.; Thornbrough, Joshua M.; Dong, Beihua; Gaughan, Christina; Elliott, Ruth

    2014-01-01

    ABSTRACT Viral 2′,5′-phosphodiesterases (2′,5′-PDEs) help disparate RNA viruses evade the antiviral activity of interferon (IFN) by degrading 2′,5′-oligoadenylate (2-5A) activators of RNase L. A kinase anchoring proteins (AKAPs) bind the regulatory subunits of protein kinase A (PKA) to localize and organize cyclic AMP (cAMP) signaling during diverse physiological processes. Among more than 43 AKAP isoforms, AKAP7 appears to be unique in its homology to viral 2′,5′-PDEs. Here we show that mouse AKAP7 rapidly degrades 2-5A with kinetics similar to that of murine coronavirus (mouse hepatitis virus [MHV]) strain A59 ns2 and human rotavirus strain WA VP3 proteins. To determine whether AKAP7 could substitute for a viral 2′,5′-PDE, we inserted AKAP7 cDNA into an MHV genome with an inactivated ns2 gene. The AKAP7 PDE domain or N-terminally truncated AKAP7 (both lacking a nuclear localization motif), but not full-length AKAP7 or a mutant, AKAP7H185R, PDE domain restored the infectivity of ns2 mutant MHV in bone marrow macrophages and in livers of infected mice. Interestingly, the AKAP7 PDE domain and N-terminally deleted AKAP7 were present in the cytoplasm (the site of MHV replication), whereas full-length AKAP7 was observed only in nuclei. We suggest the possibility that viral acquisition of the host AKAP7 PDE domain might have occurred during evolution, allowing diverse RNA viruses to antagonize the RNase L pathway. PMID:24987090

  11. Facilitation of learning: part 1.

    PubMed

    Warburton, Tyler; Trish, Houghton; Barry, Debbie

    2016-04-06

    This article, the fourth in a series of 11, discusses the context for the facilitation of learning. It outlines the main principles and theories for understanding the process of learning, including examples which link these concepts to practice. The practical aspects of using these theories in a practice setting will be discussed in the fifth article of this series. Together, these two articles will provide mentors and practice teachers with knowledge of the learning process, which will enable them to meet the second domain of the Nursing and Midwifery Council's Standards to Support Learning and Assessment in Practice on facilitation of learning.

  12. A chimera carrying the functional domain of the orphan protein SLC7A14 in the backbone of SLC7A2 mediates trans-stimulated arginine transport.

    PubMed

    Jaenecke, Isabel; Boissel, Jean-Paul; Lemke, Matthias; Rupp, Johanna; Gasnier, Bruno; Closs, Ellen I

    2012-08-31

    In human skin fibroblasts, a lysosomal transport system specific for cationic amino acids has been described and named system c. We asked if SLC7A14 (solute carrier family 7 member A14), an orphan protein assigned to the SLC7 subfamily of cationic amino acid transporters (CATs) due to sequence homology, may represent system c. Fusion proteins between SLC7A14 and enhanced GFP localized to intracellular vesicles, co-staining with the lysosomal marker LysoTracker(®). To perform transport studies, we first tried to redirect SLC7A14 to the plasma membrane (by mutating putative lysosomal targeting motifs) but without success. We then created a chimera carrying the backbone of human (h) CAT-2 and the protein domain of SLC7A14 corresponding to the so-called "functional domain" of the hCAT proteins, a protein stretch of 81 amino acids that determines the apparent substrate affinity, sensitivity to trans-stimulation, and (as revealed in this study) pH dependence. The chimera mediated arginine transport and exhibited characteristics similar but not identical to hCAT-2A (the low affinity hCAT-2 isoform). Western blot and microscopic analyses confirmed localization of the chimera in the plasma membrane of Xenopus laevis oocytes. Noticeably, arginine transport by the hCAT-2/SLC7A14 chimera was pH-dependent, trans-stimulated, and inhibited by α-trimethyl-L-lysine, properties assigned to lysosomal transport system c in human skin fibroblasts. Expression analysis showed strong expression of SLC7A14 mRNA in these cells. Taken together, these data strongly suggest that SLC7A14 is a lysosomal transporter for cationic amino acids.

  13. Facilitating Facilitators: Enhancing PBL through a Structured Facilitator Development Program

    ERIC Educational Resources Information Center

    Salinitri, Francine D.; Wilhelm, Sheila M.; Crabtree, Brian L.

    2015-01-01

    With increasing adoption of the problem-based learning (PBL) model, creative approaches to enhancing facilitator training and optimizing resources to maintain effective learning in small groups is essential. We describe a theoretical framework for the development of a PBL facilitator training program that uses the constructivist approach as the…

  14. 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.

  15. Inhibition of the Myotoxicity Induced by Bothrops jararacussu Venom and Isolated Phospholipases A2 by Specific Camelid Single-Domain Antibody Fragments

    PubMed Central

    Prado, Nidiane D. R.; Pereira, Soraya S.; da Silva, Michele P.; Morais, Michelle S. S.; Kayano, Anderson M.; Moreira-Dill, Leandro S.; Luiz, Marcos B.; Zanchi, Fernando B.; Fuly, André L.; E. F. Huacca, Maribel; Fernandes, Cleberson F.; Calderon, Leonardo A.; Zuliani, Juliana P.; Soares, Andreimar M.; Stabeli, Rodrigo G.; F. C. Fernandes, Carla

    2016-01-01

    Antivenoms, produced using animal hyperimmune plasma, remains the standard therapy for snakebites. Although effective against systemic damages, conventional antivenoms have limited efficacy against local tissue damage. Additionally, the hypersensitivity reactions, often elicited by antivenoms, the high costs for animal maintenance, the difficulty of producing homogeneous lots, and the instability of biological products instigate the search for innovative products for antivenom therapy. In this study, camelid antibody fragments (VHH) with specificity to Bothropstoxin I and II (BthTX-I and BthTX-II), two myotoxic phospholipases from Bothrops jararacussu venom, were selected from an immune VHH phage display library. After biopanning, 28 and 6 clones recognized BthTX-I and BthTX-II by ELISA, respectively. Complementarity determining regions (CDRs) and immunoglobulin frameworks (FRs) of 13 VHH-deduced amino acid sequences were identified, as well as the camelid hallmark amino acid substitutions in FR2. Three VHH clones (KF498607, KF498608, and KC329718) were capable of recognizing BthTX-I by Western blot and showed affinity constants in the nanomolar range against both toxins. VHHs inhibited the BthTX-II phospholipase A2 activity, and when tested for cross-reactivity, presented specificity to the Bothrops genus in ELISA. Furthermore, two clones (KC329718 and KF498607) neutralized the myotoxic effects induced by B. jararacussu venom, BthTX-I, BthTX-II, and by a myotoxin from Bothrops brazili venom (MTX-I) in mice. Molecular docking revealed that VHH CDRs are expected to bind the C-terminal of both toxins, essential for myotoxic activity, and to epitopes in the BthTX-II enzymatic cleft. Identified VHHs could be a biotechnological tool to improve the treatment for snake envenomation, an important and neglected world public health problem. PMID:27028872

  16. The Inhibitory Effect of α/β-Hydrolase Domain-Containing 6 (ABHD6) on the Surface Targeting of GluA2- and GluA3-Containing AMPA Receptors

    PubMed Central

    Wei, Mengping; Jia, Moye; Zhang, Jian; Yu, Lulu; Zhao, Yunzhi; Chen, Yingqi; Ma, Yimeng; Zhang, Wei; Shi, Yun S.; Zhang, Chen

    2017-01-01

    The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors (AMPARs) are major excitatory receptors that mediate fast neurotransmission in the mammalian brain. The surface expression of functional AMPARs is crucial for synaptic transmission and plasticity. AMPAR auxiliary subunits control the biosynthesis, membrane trafficking, and synaptic targeting of AMPARs. Our previous report showed that α/β-hydrolase domain-containing 6 (ABHD6), an auxiliary subunit for AMPARs, suppresses the membrane delivery and function of GluA1-containing receptors in both heterologous cells and neurons. However, it remained unclear whether ABHD6 affects the membrane trafficking of glutamate receptor subunits, GluA2 and GluA3. Here, we examine the effects of ABHD6 overexpression in HEK293T cells expressing GluA1, GluA2, GluA3, and stargazin, either alone or in combination. The results show that ABHD6 suppresses the glutamate-induced currents and the membrane expression of AMPARs when expressing GluA2 or GluA3 in the HEK293T cells. We generated a series of GluA2 and GluA3 C-terminal deletion constructs and confirm that the C-terminus of GluAs is required for ABHD6’s inhibitory effects on glutamate-induced currents and surface expression of GluAs. Meanwhile, our pull-down experiments reveal that ABHD6 binds to GluA1–3, and deletion of the C-terminal domain of GluAs abolishes this binding. These findings demonstrate that ABHD6 inhibits the AMPAR-mediated currents and its surface expression, independent of the type of AMPAR subunits, and this inhibitor’s effects are mediated through the binding with the GluAs C-terminal regions. PMID:28303090

  17. Bis-Retinoid A2E Induces an Increase of Basic Fibroblast Growth Factor via Inhibition of Extracellular Signal-Regulated Kinases 1/2 Pathway in Retinal Pigment Epithelium Cells and Facilitates Phagocytosis

    PubMed Central

    Balmer, Delphine; Bapst-Wicht, Linda; Pyakurel, Aswin; Emery, Martine; Nanchen, Natacha; Bochet, Christian G.; Roduit, Raphael

    2017-01-01

    Age-related macular degeneration (ARMD) is the leading cause of vision loss in developed countries. Hallmarks of the disease are well known; indeed, this pathology is characterized by lipofuscin accumulation, is principally composed of lipid-containing residues of lysosomal digestion. The N-retinyl-N-retinylidene ethanolamine (A2E) retinoid which is thought to be a cytotoxic component for RPE is the best-characterized component of lipofuscin so far. Even if no direct correlation between A2E spatial distribution and lipofuscin fluorescence has been established in aged human RPE, modified forms or metabolites of A2E could be involved in ARMD pathology. Mitogen-activated protein kinase (MAPK) pathways have been involved in many pathologies, but not in ARMD. Therefore, we wanted to analyze the effects of A2E on MAPKs in polarized ARPE19 and isolated mouse RPE cells. We showed that long-term exposure of polarized ARPE19 cells to low A2E dose induces a strong decrease of the extracellular signal-regulated kinases' (ERK1/2) activity. In addition, we showed that A2E, via ERK1/2 decrease, induces a significant decrease of the retinal pigment epithelium-specific protein 65 kDa (RPE65) expression in ARPE19 cells and isolated mouse RPE. In the meantime, we showed that the decrease of ERK1/2 activity mediates an increase of basic fibroblast growth factor (bFGF) mRNA expression and secretion that induces an increase in phagocytosis via a paracrine effect. We suggest that the accumulation of deposits coming from outer segments (OS) could be explained by both an increase of bFGF-induced phagocytosis and by the decrease of clearance by A2E. The bFGF angiogenic protein may therefore be an attractive target to treat ARMD. PMID:28298893

  18. Genomic characterization and dynamic methylation of promoter facilitates transcriptional regulation of H2A variants, H2A.1 and H2A.2 in various pathophysiological states of hepatocyte.

    PubMed

    Tyagi, Monica; Reddy, Divya; Gupta, Sanjay

    2017-02-03

    Differential expression of homomorphous variants of H2A family of histone H2A.1 and H2A.2 have been associated with hepatocellular carcinoma and maintenance of undifferentiated state of hepatocyte. However, not much is known about the transcriptional regulation of these H2A variants. The current study revealed the presence of 43bp 5'-regulatory region upstream of translation start site and a 26bp 3' stem loop conserved region for both the H2A.1 and H2A.2 variants. However, alignment of both H2A.1 and H2A.2 5'-untranslated region (UTR) sequences revealed no significant degree of homology between them despite the coding exon being very similar amongst the variants. Further, transient transfection coupled with dual luciferase assay of cloned 5' upstream sequences of H2A.1 and H2A.2 of length 1.2 (-1056 to +144) and 1.379kb (-1160 to +219) from experimentally identified 5'UTR in rat liver cell line (CL38) confirmed their promoter activity. Moreover, in silico analysis revealed a presence of multiple CpG sites interspersed in the cloned promoter of H2A.1 and a CpG island near TSS for H2A.2, suggesting that histone variants transcription might be regulated epigenetically. Indeed, treatment with DNMT and HDAC inhibitors increased the expression of H2A.2 with no significant change in H2A.1 levels. Further, methyl DNA immunoprecipitation coupled with quantitative analysis of DNA methylation using real-time PCR revealed hypo-methylation and hyper-methylation of H2A.1 and H2A.2 respectively in embryonic and HCC compared to control adult liver tissue. Collectively, the data suggests that differential DNA methylation on histone promoters is a dynamic player regulating their expression status in different pathophysiological stages of liver.

  19. Sequencing and characterization of mixed function monooxygenase genes CYP1A1 and CYP1A2 of Mink (Mustela vison) to facilitate study of dioxin-like compounds

    SciTech Connect

    Zhang Xiaowei; Moore, Jeremy N.; Newsted, John L.; Hecker, Markus Zwiernik, Matthew J.; Jones, Paul D.; Bursian, Steven J.

    2009-02-01

    As part of an ongoing effort to understand aryl hydrocarbon receptor (AhR) mediated toxicity in mink, cDNAs encoding for CYP1A1 and the CYP1A2 mixed function monooxygenases were cloned and characterized. In addition, the effects of selected dibenzofurans on the expression of these genes and the presence of their respective proteins (P4501A) were investigated, and then correlated with the catalytic activities of these proteins as measured by ethoxyresorufin O-deethylase (EROD) and methoxyresorufin O-deethylase (MROD) activities. The predicted protein sequences for CYP1A1 and CYP1A2 comprise 517 and 512 amino acid residues, respectively. The phylogenetic analysis of the mink CYP1As with protein sequences of other mammals revealed high sequence homology with sea otter, seals and the dog, with amino acid identities ranging from 89 to 95% for CYP1A1 and 81 to 93% for CYP1A2. Since exposure to both 2,3,7,8-Tetrachlorodibenzofuran (TCDF) and 2,3,4,7,8-Pentachlorodibenzofuran (PeCDF) resulted in dose-dependent increases of CYP1A1 mRNA, CYP1A2 mRNA and CYP1A protein levels an underlying AhR-mediated mechanism is suggested. The up-regulation of CYP1A mRNA in liver was more consistent to the sum adipose TEQ concentration than to the liver TEQ concentration in minks treated with TCDF or PeCDF. The result suggested that the hepatic-sequestered fraction of PeCDF was biologically inactive to the induction of CYP1A1 and CYP1A2.

  20. Sound Symbolism Facilitates Early Verb Learning

    ERIC Educational Resources Information Center

    Imai, Mutsumi; Kita, Sotaro; Nagumo, Miho; Okada, Hiroyuki

    2008-01-01

    Some words are sound-symbolic in that they involve a non-arbitrary relationship between sound and meaning. Here, we report that 25-month-old children are sensitive to cross-linguistically valid sound-symbolic matches in the domain of action and that this sound symbolism facilitates verb learning in young children. We constructed a set of novel…

  1. Cell Surface Expression Level Variation between Two Common Human Leukocyte Antigen Alleles, HLA-A2 and HLA-B8, Is Dependent on the Structure of the C Terminal Part of the Alpha 2 and the Alpha 3 Domains

    PubMed Central

    Dellgren, Christoffer; Nehlin, Jan O.; Barington, Torben

    2015-01-01

    Constitutive cell surface expression of Human Leukocyte Antigen (HLA) class I antigens vary extremely from tissue to tissue and individual antigens may differ widely in expression levels. Down-regulation of class I expression is a known immune evasive mechanism used by cancer cells and viruses. Moreover, recent observations suggest that even minor differences in expression levels may influence the course of viral infections and the frequency of complications to stem cell transplantation. We have shown that some human multipotent stem cells have high expression of HLA-A while HLA-B is only weakly expressed, and demonstrate here that this is also the case for the human embryonic kidney cell line HEK293T. Using quantitative flow cytometry and quantitative polymerase chain reaction we found expression levels of endogenous HLA-A3 (median 71,204 molecules per cell) 9.2-fold higher than the expression of-B7 (P = 0.002). Transfection experiments with full-length HLA-A2 and -B8 encoding plasmids confirmed this (54,031 molecules per cell vs. 2,466, respectively, P = 0.001) independently of transcript levels suggesting a post-transcriptional regulation. Using chimeric constructs we found that the cytoplasmic tail and the transmembrane region had no impact on the differential cell surface expression. In contrast, ~65% of the difference could be mapped to the six C-terminal amino acids of the alpha 2 domain and the alpha 3 domain (amino acids 176–284), i.e. amino acids not previously shown to be of importance for differential expression levels of HLA class I molecules. We suggest that the differential cell surface expression of two common HLA-A and–B alleles is regulated by a post-translational mechanism that may involve hitherto unrecognized molecules. PMID:26258424

  2. Facilitating Organizational Change.

    ERIC Educational Resources Information Center

    1999

    The first of the three papers in this symposium, "Conflicts that Arise in Small Group Facilitation: A Descriptive Study of Accounts, Actions, Outcomes, and Assessments" (Judith A. Kolb, William J. Rothwell), contains self-report verbatim accounts contributed by facilitators and the results of a literature review on small group conflict.…

  3. Evaluator or Facilitator.

    ERIC Educational Resources Information Center

    Bolding, James T.

    1978-01-01

    In American schools, the classroom teacher must act in two conflicting capacities: as a facilitator of learning and as an evaluator of his own facilitating activities. To avoid problems inherent in this, the evaluator role could be assigned elsewhere, as in the Boy Scouts' merit badge system. (SJL)

  4. Monitoring disappearance of monomers and generation of resistance to proteolysis during the formation of the activation domain of human procarboxypeptidase A2 (ADA2h) amyloid fibrils by matrix-assisted laser-desorption ionization-time-of-flight-MS.

    PubMed Central

    Villanueva, Josep; Villegas, Virtudes; Querol, Enrique; Avilés, Francesc X; Serrano, Luis

    2003-01-01

    The term 'amyloidosis' is used to represent a group of protein misfolding diseases characterized by the polymerization of normally innocuous and soluble proteins or peptides into insoluble proteinaceous deposits. One of the several questions that remain unclear regarding the process of amyloid fibril formation is related to the status of the protein when such a process begins. Protein engineering is one of the selected approaches to study amyloidosis. Characterization of many variants of a protein can give information about why a soluble protein aggregates to form fibrils. In the present study, we report information on the conformational changes that precede the formation of fibrils, monitored by the complementary use of exoproteolysis and matrix-assisted laser-desorption ionization-time-of-flight-MS. This is a novel application of an easy and fast approach. In addition, we used it to evaluate the ability of the model protein ADA2h (activation domain of human procarboxypeptidase A2) and their mutants to generate amyloid fibrils. It could be a useful test to screen protein variants and to study to what extent some physicochemical parameters affect fibrillogenesis. PMID:12765547

  5. Facilitating Understandings of Geometry.

    ERIC Educational Resources Information Center

    Pappas, Christine C.; Bush, Sara

    1989-01-01

    Illustrates some learning encounters for facilitating first graders' understanding of geometry. Describes some of children's approaches using Cuisenaire rods and teacher's intervening. Presents six problems involving various combinations of Cuisenaire rods and cubes. (YP)

  6. Ligand binding by PDZ domains.

    PubMed

    Chi, Celestine N; Bach, Anders; Strømgaard, Kristian; Gianni, Stefano; Jemth, Per

    2012-01-01

    The postsynaptic density protein-95/disks large/zonula occludens-1 (PDZ) protein domain family is one of the most common protein-protein interaction modules in mammalian cells, with paralogs present in several hundred human proteins. PDZ domains are found in most cell types, but neuronal proteins, for example, are particularly rich in these domains. The general function of PDZ domains is to bring proteins together within the appropriate cellular compartment, thereby facilitating scaffolding, signaling, and trafficking events. The many functions of PDZ domains under normal physiological as well as pathological conditions have been reviewed recently. In this review, we focus on the molecular details of how PDZ domains bind their protein ligands and their potential as drug targets in this context.

  7. [Drug facilitated sexual assault].

    PubMed

    Alempijević, Djordje; Savić, Slobodan; Stojanović, Jovan; Spasić, Andjelka

    2007-01-01

    In line with the fact that there is little information regarding drug facilitated sexual assault in national medical literature, the authors aimed to prepare a review of the phenomenon based on available international references. Therefore we offered a definition of the concept of sexual assault, and rape in particular. Consent and ability for valid consent for sexual intercourse were defined as well. A review contains discussion about the basic elements of a concept of drug-facilitated sexual assault. There is also available information in regard to pharmacology of common data rape drugs, i.e. flunitrazepam, gamma-hydroxybutyrate (GHB), and ketamine. We indicate the utmost importance of prompt collecting of biological samples for toxicological screening in patients who are suspected victims of drug facilitated sexual assault.

  8. Understanding Facilitation: Theory and Principles.

    ERIC Educational Resources Information Center

    Hogan, Christine

    This book introduces newcomers to the concept of facilitation, and it presents a critical analysis of established and current theory on facilitation for existing practitioners. The following are among the topics discussed: (1) emergence of the field of facilitation; (2) development of facilitation in management; (3) development of facilitation in…

  9. Facilitation of Adult Development

    ERIC Educational Resources Information Center

    Boydell, Tom

    2016-01-01

    Taking an autobiographical approach, I tell the story of my experiences facilitating adult development, in a polytechnic and as a management consultant. I relate these to a developmental framework of Modes of Being and Learning that I created and elaborated with colleagues. I connect this picture with a number of related models, theories,…

  10. Facilitator's Guide: Censorship Workshop.

    ERIC Educational Resources Information Center

    Layden, Kent

    To help leaders or "facilitators" of a series of simulation exercises on controversial issues for school board members, this guide describes how the simulations work and provides some of the materials required for the simulation exercise on censorship and book banning. After defining simulation or gaming exercises, the author notes the…

  11. Facilitating Distance Education.

    ERIC Educational Resources Information Center

    Rossman, Mark H., Ed.; Rossman, Maxine E., Ed.

    1995-01-01

    This collection of articles on distance learning reflects the perspectives and concerns of the learner and the facilitator of learning in distance education setting. Eight chapters are included: (1) "The Evolution and Advantages of Distance Education" (John E. Cantelon) traces the history of distance education and demonstrates how it transcends…

  12. Facilitative Strategies in Action.

    ERIC Educational Resources Information Center

    Fuller, Thara M. A.; Haugabrook, Adrian K.

    2001-01-01

    Describes campus-based strategies to facilitate collaboration by examining the process of restructuring a division of student affairs as an educational partner with academic affairs. Describes three collaborative efforts at the University of Massachusetts Boston: the Beacon Leadership Project, the Diversity Research Initiative, and the Beacon…

  13. The Inclusion Facilitator's Guide

    ERIC Educational Resources Information Center

    Jorgensen, Cheryl M.; Schuh, Mary C.; Nisbet, Jan

    2005-01-01

    Inclusion facilitators are educators who do more than teach children with disabilities--they advocate for change in schools and communities, sparking a passion for inclusion in teachers, administrators, and families and giving them the practical guidance they need to make it work. This is an essential new role in today's schools, and this guide…

  14. Program Facilitates Distributed Computing

    NASA Technical Reports Server (NTRS)

    Hui, Joseph

    1993-01-01

    KNET computer program facilitates distribution of computing between UNIX-compatible local host computer and remote host computer, which may or may not be UNIX-compatible. Capable of automatic remote log-in. User communicates interactively with remote host computer. Data output from remote host computer directed to local screen, to local file, and/or to local process. Conversely, data input from keyboard, local file, or local process directed to remote host computer. Written in ANSI standard C language.

  15. Single-domain antibodies for biomedical applications.

    PubMed

    Krah, Simon; Schröter, Christian; Zielonka, Stefan; Empting, Martin; Valldorf, Bernhard; Kolmar, Harald

    2016-01-01

    Single-domain antibodies are the smallest antigen-binding units of antibodies, consisting either only of one variable domain or one engineered constant domain that solely facilitates target binding. This class of antibody derivatives comprises naturally occurring variable domains derived from camelids and sharks as well as engineered human variable or constant antibody domains of the heavy or light chain. Because of their high affinity and specificity as well as stability, small size and benefit of multiple re-formatting opportunities, those molecules emerged as promising candidates for biomedical applications and some of these entities have already proven to be successful in clinical development.

  16. A 2D-QSAR and Grid-Independent Molecular Descriptor (GRIND) Analysis of Quinoline-Type Inhibitors of Akt2: Exploration of the Binding Mode in the Pleckstrin Homology (PH) Domain

    PubMed Central

    Akhtar, Noreen; Jabeen, Ishrat

    2016-01-01

    Protein kinase B-β (PKBβ/Akt2) is a serine/threonine-specific protein kinase that has emerged as one of the most important regulators of cell growth, differentiation, and division. Upregulation of Akt2 in various human carcinomas, including ovarian, breast, and pancreatic, is a well-known tumorigenesis phenomenon. Early on, the concept of the simultaneous administration of anticancer drugs with inhibitors of Akt2 was advocated to overcome cell proliferation in the chemotherapeutic treatment of cancer. However, clinical studies have not lived up to the high expectations, and several phase II and phase III clinical studies have been terminated prematurely because of severe side effects related to the non-selective isomeric inhibition of Akt2. The notion that the sequence identity of pleckstrin homology (PH) domains within Akt-isoforms is less than 30% might indicate the possibility of the development of selective antagonists against the Akt2 PH domain. Therefore, in this study, various in silico tools were utilized to explore the hypothesis that quinoline-type inhibitors bind in the Akt2 PH domain. A Grid-Independent Molecular Descriptor (GRIND) analysis indicated that two hydrogen bond acceptors, two hydrogen bond donors and one hydrophobic feature at a certain distance from each other were important for the selective inhibition of Akt2. Our docking results delineated the importance of Lys30 as an anchor point for mapping the distances of important amino acid residues in the binding pocket, including Lys14, Glu17, Arg25, Asn53, Asn54 and Arg86. The binding regions identified complement the GRIND-based pharmacophoric features. PMID:28036396

  17. Task Integration Facilitates Multitasking

    PubMed Central

    de Oliveira, Rita F.; Raab, Markus; Hegele, Mathias; Schorer, Jörg

    2017-01-01

    The aim of this study was to investigate multi-task integration in a continuous tracking task. We were particularly interested in how manipulating task structure in a dual-task situation affects learning of a constant segment embedded in a pursuit-tracking task. Importantly, we examined if dual-task effects could be attributed to task integration by varying the structural similarity and difficulty of the primary and secondary tasks. In Experiment 1 participants performed a pursuit tracking task while counting high-pitched tones and ignoring low-pitched tones. The tones were either presented randomly or structurally 250 ms before each tracking turn. Experiment 2 increased the motor load of the secondary tasks by asking participants to tap their feet to the tones. Experiment 3 further increased motor load of the primary task by increasing its speed and having participants tracking with their non-dominant hand. The results show that dual-task interference can be moderated by secondary task conditions that match the structure of the primary task. Therefore our results support proposals of task integration in continuous tracking paradigms. We conclude that multi-tasking is not always detrimental for motor learning but can be facilitated through task-integration. PMID:28360878

  18. Task Integration Facilitates Multitasking.

    PubMed

    de Oliveira, Rita F; Raab, Markus; Hegele, Mathias; Schorer, Jörg

    2017-01-01

    The aim of this study was to investigate multi-task integration in a continuous tracking task. We were particularly interested in how manipulating task structure in a dual-task situation affects learning of a constant segment embedded in a pursuit-tracking task. Importantly, we examined if dual-task effects could be attributed to task integration by varying the structural similarity and difficulty of the primary and secondary tasks. In Experiment 1 participants performed a pursuit tracking task while counting high-pitched tones and ignoring low-pitched tones. The tones were either presented randomly or structurally 250 ms before each tracking turn. Experiment 2 increased the motor load of the secondary tasks by asking participants to tap their feet to the tones. Experiment 3 further increased motor load of the primary task by increasing its speed and having participants tracking with their non-dominant hand. The results show that dual-task interference can be moderated by secondary task conditions that match the structure of the primary task. Therefore our results support proposals of task integration in continuous tracking paradigms. We conclude that multi-tasking is not always detrimental for motor learning but can be facilitated through task-integration.

  19. Program Facilitates CMMI Appraisals

    NASA Technical Reports Server (NTRS)

    Sweetser, Wesley

    2005-01-01

    A computer program has been written to facilitate appraisals according to the methodology of Capability Maturity Model Integration (CMMI). [CMMI is a government/industry standard, maintained by the Software Engineering Institute at Carnegie Mellon University, for objectively assessing the engineering capability and maturity of an organization (especially, an organization that produces software)]. The program assists in preparation for a CMMI appraisal by providing drop-down lists suggesting required artifacts or evidence. It identifies process areas for which similar evidence is required and includes a copy feature that reduces or eliminates repetitive data entry. It generates reports to show the entire framework for reference, the appraisal artifacts to determine readiness for an appraisal, and lists of interviewees and questions to ask them during the appraisal. During an appraisal, the program provides screens for entering observations and ratings, and reviewing evidence provided thus far. Findings concerning strengths and weaknesses can be exported for use in a report or a graphical presentation. The program generates a chart showing capability level ratings of the organization. A context-sensitive Windows help system enables a novice to use the program and learn about the CMMI appraisal process.

  20. The calcium sensor synaptotagmin 7 is required for synaptic facilitation

    PubMed Central

    Jackman, Skyler L.; Turecek, Josef; Belinsky, Justine E.

    2015-01-01

    It has been known for over 70 years that synaptic strength is dynamically regulated in a use-dependent manner1. At synapses with a low initial release probability, closely spaced presynaptic action potentials can result in facilitation, a short-term form of enhancement where each subsequent action potential evokes greater neurotransmitter release2. Facilitation can enhance neurotransmitter release manyfold and profoundly influence information transfer across synapses3, but the underlying mechanism remains a mystery. Among the proposed mechanisms is that a specialized calcium sensor for facilitation transiently increases the probability of release2,4 and is distinct from the fast sensors that mediate rapid neurotransmitter release. Yet such a sensor has never been identified, and its very existence has been disputed5,6. Here we show that synaptotagmin 7 (syt7) is a calcium sensor that is required for facilitation at multiple central synapses. In syt7 knockout mice, facilitation is eliminated even though the initial probability of release and presynaptic residual calcium signals are unaltered. Expression of wild-type syt7 in presynaptic neurons restored facilitation, whereas expression of a mutated syt7 with a calcium-insensitive C2A domain did not. By revealing the role of syt7 in synaptic facilitation, these results resolve a longstanding debate about a widespread form of short-term plasticity, and will enable future studies that may lead to a deeper understanding of the functional importance of facilitation. PMID:26738595

  1. Facilitating Dialogues about Racial Realities

    ERIC Educational Resources Information Center

    Quaye, Stephen John

    2014-01-01

    Background/Context: Facilitating dialogues about racial issues in higher education classroom settings continues to be a vexing problem facing postsecondary educators. In order for students to discuss race with their peers, they need skilled facilitators who are knowledgeable about racial issues and able to support students in these difficult…

  2. Facilitated Communication in Mainstream Schools.

    ERIC Educational Resources Information Center

    Remington-Gurney, Jane; Crossley, Rosemary

    Facilitated communication is described as a method of training communication partners or facilitators to provide physical assistance to communication aid users, to help them overcome physical and emotional problems in using their aids. In Melbourne (Victoria, Australia), the DEAL (Dignity, Education and Language) Centre has identified 96 people…

  3. A Manual for Group Facilitators.

    ERIC Educational Resources Information Center

    Auvine, Brian; And Others

    This resource manual presents guidelines and effective techniques for people who want to acquire group facilitation skills. It is a valuable resource for anyone planning or presenting a workshop; trainers or teachers interested in innovative classroom techniques; and anyone involved in a group as leader, facilitator, or participant. The manual…

  4. Treatment adherence and facilitator characteristics in a community based pediatric weight control intervention

    PubMed Central

    2014-01-01

    Background There is a pressing need to develop effective and broadly accessible interventions to address pediatric obesity. An important dimension in translating interventions to community settings is evaluating the fidelity with which the intended treatment is delivered and the level of facilitator needed to deliver the intervention with efficacy. Purpose The primary objectives of this study were to: 1) provide descriptive information regarding adherence to protocol and non-specific facilitator characteristics (e.g. interpersonal characteristics, group management skills) within the context of a community based pediatric weight control intervention delivered by paraprofessionals; and 2) examine the relationships among facilitator adherence and characteristics and rate of change in percent overweight demonstrated by youth over the course of the 24-week intervention. Methods The intervention was conducted between February and September of 2011. Children (6–16 years) and parents completed primary outcome measures at baseline, 12, and 24 weeks (i.e. end of treatment). A 2-part rating form was developed to assess facilitator adherence to weekly content and general provider characteristics at two different time points during the intervention. Results Youth participating in this study were on average 11.3 years old (SD = 2.8), with most being under the age of 13 years (74.2%). Over half were female (54.8%) and over two-thirds were White (68.4%). On average, facilitators adhered to 96.0% (SD = 5.2%) of the session content at Time 1 and 92.6% (SD = 6.8%) at Time 2. Higher Content Adherence at Time 1 and Time 2 were associated with greater loss in percent overweight. Conclusions Our data suggest that paraprofessionals without prior expertise in pediatric weight control can be trained to successfully deliver an intervention that is evidence based and incorporates behavioral and educational components. These findings need to be considered in light of some

  5. 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

  6. 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…

  7. Social Facilitation of Aiding Responses.

    ERIC Educational Resources Information Center

    Bartell, Patricia; And Others

    Research on individual's response to emergency situations in the presence of others has produced conflicting results. The bystander effect is the label applied to inaction or the unlikelihood of assistance with others present. The social facilitation effect occurs when the presence of others energizes response; strong habit responses are…

  8. Facilitating Creativity in Adult Learners

    ERIC Educational Resources Information Center

    Tsai, Kuan Chen

    2013-01-01

    Creativity in education research has received increasing attention, although the major focus of this research has been on children. Despite pleas by several adult educators for promoting creativity, very few studies have focused on adult learners, leaving to it to be explored what approaches are useful for adult educators to facilitate creativity…

  9. SUPERFUND GROUNDWATER ISSUE - FACILITATED TRANSPORT

    EPA Science Inventory

    The Regional Superfund Ground Water Forum is a group of ground-water scientists representing EPA's Regional Superfund Offices, organized to exchange up to date information related to ground-water remediation at Superfund sites. Facilitated transport is an issue identified by the ...

  10. Facilitating Conditions for School Motivation.

    ERIC Educational Resources Information Center

    Yeung, Alexander Seeshing; McInerney, Dennis M.

    Primary and high school students (277 in grades 5-6; 615 in grades 7-12) in the United States (47 percent boys) responded to 26 items of the Facilitating Conditions Questionnaire (FCQ). Results indicate 7 distinct FCQ factors: perceived value of schooling; affect toward schooling; peer positive academic climate (Peer Positive); encouragement from…

  11. Parietal connectivity mediates multisensory facilitation.

    PubMed

    Brang, David; Taich, Zachary J; Hillyard, Steven A; Grabowecky, Marcia; Ramachandran, V S

    2013-09-01

    Our senses interact in daily life through multisensory integration, facilitating perceptual processes and behavioral responses. The neural mechanisms proposed to underlie this multisensory facilitation include anatomical connections directly linking early sensory areas, indirect connections to higher-order multisensory regions, as well as thalamic connections. Here we examine the relationship between white matter connectivity, as assessed with diffusion tensor imaging, and individual differences in multisensory facilitation and provide the first demonstration of a relationship between anatomical connectivity and multisensory processing in typically developed individuals. Using a whole-brain analysis and contrasting anatomical models of multisensory processing we found that increased connectivity between parietal regions and early sensory areas was associated with the facilitation of reaction times to multisensory (auditory-visual) stimuli. Furthermore, building on prior animal work suggesting the involvement of the superior colliculus in this process, using probabilistic tractography we determined that the strongest cortical projection area connected with the superior colliculus includes the region of connectivity implicated in our independent whole-brain analysis.

  12. Facilitation of Mourning During Childhood.

    ERIC Educational Resources Information Center

    Kliman, Gilbert; And Others

    This paper discusses case studies of children psychologically disturbed by the death of parents or siblings. Illustrations of mourning facilitation were mainly gathered from 16 orphaned children, ages 3-14. Some techniques used in helping children mourn include: discussing physical details of the illness, discussing previous deaths of animals and…

  13. 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.

  14. Classification and Lineage Tracing of SH2 Domains Throughout Eukaryotes.

    PubMed

    Liu, Bernard A

    2017-01-01

    Today there exists a rapidly expanding number of sequenced genomes. Cataloging protein interaction domains such as the Src Homology 2 (SH2) domain across these various genomes can be accomplished with ease due to existing algorithms and predictions models. An evolutionary analysis of SH2 domains provides a step towards understanding how SH2 proteins integrated with existing signaling networks to position phosphotyrosine signaling as a crucial driver of robust cellular communication networks in metazoans. However organizing and tracing SH2 domain across organisms and understanding their evolutionary trajectory remains a challenge. This chapter describes several methodologies towards analyzing the evolutionary trajectory of SH2 domains including a global SH2 domain classification system, which facilitates annotation of new SH2 sequences essential for tracing the lineage of SH2 domains throughout eukaryote evolution. This classification utilizes a combination of sequence homology, protein domain architecture and the boundary positions between introns and exons within the SH2 domain or genes encoding these domains. Discrete SH2 families can then be traced across various genomes to provide insight into its origins. Furthermore, additional methods for examining potential mechanisms for divergence of SH2 domains from structural changes to alterations in the protein domain content and genome duplication will be discussed. Therefore a better understanding of SH2 domain evolution may enhance our insight into the emergence of phosphotyrosine signaling and the expansion of protein interaction domains.

  15. Facilitating Facilitators to Facilitate, in Problem or Enquiry Based Learning Sessions

    ERIC Educational Resources Information Center

    Coelho, Catherine

    2014-01-01

    Problem based learning (PBL) has been used in dental education over the past 20 years and uses a patient case scenario to stimulate learning in a small group setting, where a trained facilitator does not teach but guides the group to bring about deep contextualized learning, to be empathetic to each other and to encourage fair and equitable…

  16. 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.

  17. Sound symbolism facilitates early verb learning.

    PubMed

    Imai, Mutsumi; Kita, Sotaro; Nagumo, Miho; Okada, Hiroyuki

    2008-10-01

    Some words are sound-symbolic in that they involve a non-arbitrary relationship between sound and meaning. Here, we report that 25-month-old children are sensitive to cross-linguistically valid sound-symbolic matches in the domain of action and that this sound symbolism facilitates verb learning in young children. We constructed a set of novel sound-symbolic verbs whose sounds were judged to match certain actions better than others, as confirmed by adult Japanese- as well as English speakers, and by 2- and 3-year-old Japanese-speaking children. These sound-symbolic verbs, together with other novel non-sound-symbolic verbs, were used in a verb learning task with 3-year-old Japanese children. In line with the previous literature, 3-year-olds could not generalize the meaning of novel non-sound-symbolic verbs on the basis of the sameness of action. However, 3-year-olds could correctly generalize the meaning of novel sound-symbolic verbs. These results suggest that iconic scaffolding by means of sound symbolism plays an important role in early verb learning.

  18. Stochastic facilitation in the brain?

    NASA Astrophysics Data System (ADS)

    Ward, Lawrence M.; Greenwood, Priscilla E.

    2016-05-01

    We describe the context for three unsolved problems of noise in the brain as well as provide some new results relevant to one of them. The problems are: are neural oscillations better described as noisy limit cycles or as noise-driven quasicycles, does noise facilitate synchronization and information transmission in the brain, and do noise-driven spatial patterns (quasipatterns) coexist with noise-driven quasicycles in the brain? We provide a few new results indicating that, in models at least, spatial quasipatterns of quasicycles can occur, and resemble patterns observed in other areas, such as predator-prey systems and chemical reactions.

  19. The Influence of Facilitator and Facilitation Characteristics on Participants' Ratings of Stepfamily Education

    ERIC Educational Resources Information Center

    Higginbotham, Brian J.; Myler, Cory

    2010-01-01

    We examine the relative importance of facilitator and facilitation characteristics on participant ratings of a stepfamily education program. Data from 48 facilitators and 598 participants suggest that quality facilitation is more meaningful to participants than whether facilitators have comparable demographic characteristics or life experiences.…

  20. Facilitating submetering implementation. Final report

    SciTech Connect

    Bowers, M.A.

    1996-05-01

    Residential submetering is the measurement and billing of electric use in individual apartments in master-metered buildings. In master-metered building situations, residents do not bear electricity costs in proportion to consumption levels. As a result, studies have confirmed that residents in master-metered buildings tend to consume more electricity than residents with individual apartment metering, and have established electrical submetering as an effective energy conservation measure. The New York State Energy Research & Development Authority (NYSERDA) has commissioned a project called Facilitating Submetering Implementation to identify and analyze barriers to the implementation of residential electrical submetering in New York and to formulate recommendations that would facilitate the removal of these barriers, streamlining the process. Experienced professionals in the technical, legal, regulatory, analytical, financial, and other aspects of submetering were retained to interview key interested parties and conduct public forums. This and other data were then analyzed to ascertain the barriers to submetering and develop recommendations designed to reduce or eliminate these barriers. The key barriers to submetering implementation were found to be the Public Service Commission (PSC) requirement for a vote of a majority of shareholders (for coops and condos) and the high initial cost that cannot easily be recouped by owners of both rental and shareholder-owned buildings. The key recommendations are to repeal the voting requirement, maintain the utility incentives, adopt a uniform dispute resolution mechanism, and increase awareness through an Ad-hoc Submetering Committee and supporting educational materials. Other funding sources not fully available can also be made available with regulatory agency support.

  1. Voltage-dependent facilitation of Cx46 hemichannels

    PubMed Central

    Yin, ShengYong; Altenberg, Guillermo A.; Reuss, Luis

    2010-01-01

    Gap junction channels are formed by two hemichannels in series (one from each neighboring cell), which are in turn connexin hexamers. Under normal conditions, hemichannels at the plasma membrane are mostly closed but can be opened by changes in membrane voltage, extracellular divalent ion concentration, phosphorylation, pH, and redox potential. Recently, interactions between channels have been found to modulate the activity of several ion channels, including gap junction channels. Here, we studied whether connexin46 (Cx46) hemichannels display such behavior. We studied the response of the Cx46 hemichannels expressed in Xenopus laevis oocytes to consecutive depolarization pulses. Hemichannels formed by wild-type Cx46 and a COOH-terminal domain truncation mutant (Cx46ΔCT) were activated by voltage pulses. When the hemichannels were depolarized repeatedly from −60 mV to +80 mV, the amplitude of the outward and tail currents increased progressively with successive pulses. This phenomenon (“current facilitation”) depended on the amplitude of the depolarization, reaching a maximum at approximately +60 mV in oocytes expressing Cx46, and on the interval between pulses, disappearing with intervals longer than about 20 s. The current facilitation was also present in oocytes expressing Cx46ΔCT, ruling out a primary role of this domain in the facilitation. Nominal removal of divalent cations from the extracellular side caused maximal current activation of Cx46 and Cx46ΔCT hemichannels and prevented facilitation. The results suggest that Cx46 hemichannels show a cooperative activation independent of their COOH-terminal domain. PMID:19889966

  2. Gesture Facilitates Children's Creative Thinking.

    PubMed

    Kirk, Elizabeth; Lewis, Carine

    2017-02-01

    Gestures help people think and can help problem solvers generate new ideas. We conducted two experiments exploring the self-oriented function of gesture in a novel domain: creative thinking. In Experiment 1, we explored the relationship between children's spontaneous gesture production and their ability to generate novel uses for everyday items (alternative-uses task). There was a significant correlation between children's creative fluency and their gesture production, and the majority of children's gestures depicted an action on the target object. Restricting children from gesturing did not significantly reduce their fluency, however. In Experiment 2, we encouraged children to gesture, and this significantly boosted their generation of creative ideas. These findings demonstrate that gestures serve an important self-oriented function and can assist creative thinking.

  3. Barriers and facilitators to shelter utilization among homeless young adults.

    PubMed

    Ha, Yoonsook; Narendorf, Sarah C; Santa Maria, Diane; Bezette-Flores, Noel

    2015-12-01

    Rates of shelter use among homeless youth are low compared to use of other supportive services, yet research on barriers to shelter use has been conducted in limited regions, specifically in West Coast or Midwest cities. Additionally, while studies have generally focused on barriers to shelter use, studies on what might facilitate shelter use are lacking. This study explores barriers and facilitators to shelter use among homeless young adults from a large city in the Southwest region. Focus groups were conducted with a diverse sample of 49 homeless young adults ages 18-24. Drawing on models of health service use, findings were categorized into two domains--attitudinal and access. Themes related to attitudinal barriers include stigma/shame and self-reliance/pride. Attitudinal facilitators include the desire to extricate themselves from street life and turn their lives in a new direction. Access-related themes include barriers such as a lack of shelters and services available to meet the needs of youth, adverse shelter conditions, staff attitudes that are not acceptable to youth, restrictive shelter rules, restrictive definitions of homelessness, and a desire to differentiate themselves from older homeless individuals. Certain characteristics or circumstances (e.g., being pregnant), having supportive others, and shelters' ability to connect them to other services emerged as access facilitators to shelter use. Implications for policymakers, service providers, and future research are discussed.

  4. 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.

  5. The Teacher and Town Planner as Facilitator.

    ERIC Educational Resources Information Center

    Peel, Deborah

    2000-01-01

    Discussion of theories of facilitation in teaching focuses on citizen participation and the role of the facilitator in town planning. Highlights include hierarchies of learning; student-centered learning; facilitating community participation; information technology skills and interpersonal skills; and a rationale for participation. (LRW)

  6. Evaluation of the Facilitated Communication Pilot

    ERIC Educational Resources Information Center

    Cooper-Martin, Elizabeth

    2014-01-01

    The Office of Special Education and Student Services asked the Office of Shared Accountability to evaluate the "Facilitated Communication Pilot." In facilitated communication (FC), people with communication impairments express themselves by typing with the aid of a communication partner, called a facilitator, who provides physical (and…

  7. Technologies and Techniques for Supporting Facilitated Video

    ERIC Educational Resources Information Center

    Linnell, Natalie

    2011-01-01

    Worldwide, demand for education of all kinds is increasing beyond the capacity to provide it. One approach that shows potential for addressing this demand is facilitated video. In facilitated video, an educator is recorded teaching, and that video is sent to a remote site where it is shown to students by a facilitator who creates interaction…

  8. Fungal phylogenetic diversity drives plant facilitation.

    PubMed

    Montesinos-Navarro, Alicia; Segarra-Moragues, J G; Valiente-Banuet, A; Verdú, M

    2016-06-01

    Plant-plant facilitation is a crucial ecological process, as many plant species (facilitated) require the presence of an established individual (nurse) to recruit. Some plant facilitative interactions disappear during the ontogenetic development of the facilitated plant but others persist, even when the two plants are adults. We test whether the persistence of plant facilitative interactions is explained by the phylogenetic diversity of mutualistic and non-mutualistic fungi that the nurse and the facilitated species add to the shared rhizosphere. We classify plant facilitative interactions as persistent and non-persistent interactions and quantify the phylogenetic diversity of mutualistic and non-mutualistic fungi added by the plant species to the shared rhizosphere. Our results show that the facilitated species add less phylogenetic diversity of non-mutualistic fungi when plant facilitative interactions persist than when they do not persist. However, persistent and non-persistent facilitative interactions did not differ in the phylogenetic diversity of mutualistic fungi added by the facilitated species to the shared rhizosphere. Finally, the fungal phylogenetic diversity added by the nurse to the shared rhizosphere did not differ between persistent and non-persistent interactions. This study suggests that considering the fungal associates of the plant species involved in facilitative interactions can shed light on the mechanisms of persistence for plant-plant interactions.

  9. Effect of support group peer facilitator training programmes on peer facilitator and support group member outcomes: a systematic review

    PubMed Central

    Delisle, Vanessa C; Gumuchian, Stephanie T; Kloda, Lorie A; Boruff, Jill; El-Baalbaki, Ghassan; Körner, Annett; Malcarne, Vanessa L; Thombs, Brett D

    2016-01-01

    Objective Peer facilitators play an important role in determining the success of many support groups for patients with medical illnesses. However, many facilitators do not receive training for their role and report a number of challenges in fulfilling their responsibilities. The objective of this systematic review was to evaluate the effects of training and support programmes for peer facilitators of support groups for people with medical illnesses on (1) the competency and self-efficacy of group facilitators and (2) self-efficacy for disease management, health outcomes and satisfaction with support groups among group members. Methods Searches included the CENTRAL, CINAHL, EMBASE, MEDLINE, PsycINFO and Web of Science databases from inception through 8 April 2016; reference list reviews; citation tracking of included articles; and trial registry reviews. Eligible studies were randomised controlled trials (RCTs) in any language that evaluated the effects of training programmes for peer facilitators compared with no training or alternative training formats on (1) competency or self-efficacy of peer facilitators, and (2) self-efficacy for disease management, health outcomes and satisfaction with groups of group members. The Cochrane Risk of Bias tool was used to assess risk of bias. Results There were 9757 unique titles/abstracts and 2 full-text publications reviewed. 1 RCT met inclusion criteria. The study evaluated the confidence and self-efficacy of cancer support group facilitators randomised to 4 months access to a website and discussion forum (N=23; low resource) versus website, discussion forum and 2-day training workshop (N=29). There were no significant differences in facilitator confidence (Hedges' g=0.16, 95% CI −0.39 to 0.71) or self-efficacy (Hedges' g=0.31, 95% CI −0.24 to 0.86). Risk of bias was unclear or high for 4 of 6 domains. Conclusions Well-designed and well-conducted, adequately powered trials of peer support group facilitator training

  10. A Domain Analysis Bibliography

    DTIC Science & Technology

    1990-06-01

    Bauhaus , a prototype CASE workstation for D-SAPS development. [ARAN88A] Guillermo F. Arango. Domain Engineering for Software Reuse. PhD thesis...34 VITA90B: Domain Analysis within the ISEC Rapid Center 48 CMU/SEI-90-SR-3 Appendix III Alphabetical by Organization/Project BAUHAUS * ALLE87A

  11. 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.

  12. 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…

  13. 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…

  14. Sac phosphatase domain proteins.

    PubMed Central

    Hughes, W E; Cooke, F T; Parker, P J

    2000-01-01

    Advances in our understanding of the roles of phosphatidylinositol phosphates in controlling cellular functions such as endocytosis, exocytosis and the actin cytoskeleton have included new insights into the phosphatases that are responsible for the interconversion of these lipids. One of these is an entirely novel class of phosphatase domain found in a number of well characterized proteins. Proteins containing this Sac phosphatase domain include the yeast Saccharomyces cerevisiae proteins Sac1p and Fig4p. The Sac phosphatase domain is also found within the mammalian phosphoinositide 5-phosphatase synaptojanin and the yeast synaptojanin homologues Inp51p, Inp52p and Inp53p. These proteins therefore contain both Sac phosphatase and 5-phosphatase domains. This review describes the Sac phosphatase domain-containing proteins and their actions, with particular reference to the genetic and biochemical insights provided by study of the yeast Saccharomyces cerevisiae. PMID:10947947

  15. Cross Domain Analogies for Learning Domain Theories

    DTIC Science & Technology

    2007-01-01

    Example Problem and Worked Solution All problems and worked solutions used in this work were taken from the same physics textbook ( Giancoli 1991...domain theory. We close with a discussion of related work and our plans for the future. Representations and Problem Solving Representing physics ...small compared to the 30,000+ concepts and 8,000+ predicates already defined in the KB. Thus, objects, relations, and events that appear in physics

  16. EphrinA2 Receptor (EphA2) Is an Invasion and Intracellular Signaling Receptor for Chlamydia trachomatis

    PubMed Central

    Subbarayal, Prema; Karunakaran, Karthika; Winkler, Ann-Cathrin; Rother, Marion; Gonzalez, Erik; Meyer, Thomas F.; Rudel, Thomas

    2015-01-01

    The obligate intracellular bacterium Chlamydia trachomatis invades into host cells to replicate inside a membrane-bound vacuole called inclusion. Multiple different host proteins are recruited to the inclusion and are functionally modulated to support chlamydial development. Invaded and replicating Chlamydia induces a long-lasting activation of the PI3 kinase signaling pathway that is required for efficient replication. We identified the cell surface tyrosine kinase EphrinA2 receptor (EphA2) as a chlamydial adherence and invasion receptor that induces PI3 kinase (PI3K) activation, promoting chlamydial replication. Interfering with binding of C. trachomatis serovar L2 (Ctr) to EphA2, downregulation of EphA2 expression or inhibition of EphA2 activity significantly reduced Ctr infection. Ctr interacts with and activates EphA2 on the cell surface resulting in Ctr and receptor internalization. During chlamydial replication, EphA2 remains active accumulating around the inclusion and interacts with the p85 regulatory subunit of PI3K to support the activation of the PI3K/Akt signaling pathway that is required for normal chlamydial development. Overexpression of full length EphA2, but not the mutant form lacking the intracellular cytoplasmic domain, enhanced PI3K activation and Ctr infection. Despite the depletion of EphA2 from the cell surface, Ctr infection induces upregulation of EphA2 through the activation of the ERK pathway, which keeps the infected cell in an apoptosis-resistant state. The significance of EphA2 as an entry and intracellular signaling receptor was also observed with the urogenital C. trachomatis-serovar D. Our findings provide the first evidence for a host cell surface receptor that is exploited for invasion as well as for receptor-mediated intracellular signaling to facilitate chlamydial replication. In addition, the engagement of a cell surface receptor at the inclusion membrane is a new mechanism by which Chlamydia subverts the host cell and

  17. Scaffolding Peer-Questioning Strategies to Facilitate Meta-Cognition During Online Small Group Discussion

    ERIC Educational Resources Information Center

    Choi, Ikseon; Land, Susan M.; Turgeon, Alfred J.

    2005-01-01

    Meaningful discussion that facilitates reflective thinking can be initiated when learners raise thoughtful questions or provide critical feedback; however, generating effective questions requires a certain level of domain knowledge and meta-cognitive skills of the question-askers. We propose a peer-questioning scaffolding framework intended to…

  18. Saccharomyces SRP RNA secondary structures: a conserved S-domain and extended Alu-domain.

    PubMed

    Van Nues, Rob W; Brown, Jeremy D

    2004-01-01

    The contribution made by the RNA component of signal recognition particle (SRP) to its function in protein targeting is poorly understood. We have generated a complete secondary structure for Saccharomyces cerevisiae SRP RNA, scR1. The structure conforms to that of other eukaryotic SRP RNAs. It is rod-shaped with, at opposite ends, binding sites for proteins required for the SRP functions of signal sequence recognition (S-domain) and translational elongation arrest (Alu-domain). Micrococcal nuclease digestion of purified S. cerevisiae SRP separated the S-domain of the RNA from the Alu-domain as a discrete fragment. The Alu-domain resolved into several stable fragments indicating a compact structure. Comparison of scR1 with SRP RNAs of five yeast species related to S. cerevisiae revealed the S-domain to be the most conserved region of the RNA. Extending data from nuclease digestion with phylogenetic comparison, we built the secondary structure model for scR1. The Alu-domain contains large extensions, including a sequence with hallmarks of an expansion segment. Evolutionarily conserved bases are placed in the Alu- and S-domains as in other SRP RNAs, the exception being an unusual GU(4)A loop closing the helix onto which the signal sequence binding Srp54p assembles (domain IV). Surprisingly, several mutations within the predicted Srp54p binding site failed to disrupt SRP function in vivo. However, the strength of the Srp54p-scR1 and, to a lesser extent, Sec65p-scR1 interaction was decreased in these mutant particles. The availability of a secondary structure for scR1 will facilitate interpretation of data from genetic analysis of the RNA.

  19. 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;…

  20. Software architecture design domain

    SciTech Connect

    White, S.A.

    1996-12-31

    Software architectures can provide a basis for the capture and subsequent reuse of design knowledge. The goal of software architecture is to allow the design of a system to take place at a higher level of abstraction; a level concerned with components, connections, constraints, rationale. This architectural view of software adds a new layer of abstraction to the traditional design phase of software development. It has resulted in a flurry of activity towards techniques, tools, and architectural design languages developed specifically to assist with this activity. An analysis of architectural descriptions, even though they differ in notation, shows a common set of key constructs that are present across widely varying domains. These common aspects form a core set of constructs that should belong to any ADL in order to for the language to offer the ability to specify software systems at the architectural level. This analysis also revealed a second set of constructs which served to expand the first set thereby improving the syntax and semantics. These constructs are classified according to whether they provide representation and analysis support for architectures belonging to many varying application domains (domain-independent construct class) or to a particular application domain (domain-dependent constructs). This paper presents the constructs of these two classes, their placement in the architecture design domain and shows how they may be used to classify, select, and analyze proclaimed architectural design languages (ADLs).

  1. Simple scale interpolator facilitates reading of graphs

    NASA Technical Reports Server (NTRS)

    Fetterman, D. E., Jr.

    1965-01-01

    Simple transparent overlay with interpolation scale facilitates accurate, rapid reading of graph coordinate points. This device can be used for enlarging drawings and locating points on perspective drawings.

  2. Parental Provision of Structure: Implementation and Correlates in Three Domains

    ERIC Educational Resources Information Center

    Grolnick, Wendy S.; Raftery-Helmer, Jacquelyn N.; Marbell, Kristine N; Flamm, Elizabeth S.; Cardemil, Esteban V.

    2014-01-01

    This study examined parents' provision of "structure," defined as the organization of the environment to facilitate competence, and the degree to which it supports versus controls children's autonomy, in the domains of homework and studying, unsupervised time, and responsibilities in a diverse sample of sixth-grade children and their…

  3. Facilitation of calcium-dependent potassium current.

    PubMed

    Thompson, S H

    1994-12-01

    The activation of Ca-dependent K+ current, Ic, was studied in macropatches on the cell bodies of molluscan neurons. When a depolarizing voltage-clamp pulse was applied repeatedly, Ic facilitated in a manner that resembled the facilitation of synaptic transmitter release. Facilitation was characterized by an increase in Ic amplitude, a progressive increase in instantaneous outward current, and a decrease in utilization time. Experiments were done to investigate the mechanism responsible for Ic facilitation. Facilitation was reduced by microinjection of an exogenous Ca2+ buffer into the cytoplasm, indicating that facilitation is a Ca(2+)-dependent process. It was also reduced at elevated temperatures. Conversely, facilitation was greatly potentiated by blocking the Na/Ca exchange mechanism. It is concluded that the facilitation of Ca-dependent K+ current results from the accumulation of Ca2+ at the inner face of the membrane during the repeated activation of Ca2+ channels by depolarization. The Ca2+ indicator fluo-3 was used in fluorescence imaging experiments to measure changes in [Ca]i near the cell membrane during repeated depolarizing pulses and the interpretation of these results was aided by numerical simulations of Ca2+ accumulation, diffusion, and buffering in the peripheral cytoplasm. These experiments showed that the time course of Ic facilitation matches the time course of Ca2+ accumulation at the membrane. It was found that the strength of Ic facilitation varies among patches on the same neuron, suggesting that the accumulation of Ca2+ is not uniform along the inner surface of the membrane and that gradients in [Ca]i develop and are maintained during trains of depolarizing pulses. Potential mechanisms that may lead to local differences in Ca2+ accumulation and Ic facilitation are discussed.

  4. 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

  5. The Role of Touch in Facilitated Communication.

    ERIC Educational Resources Information Center

    Kezuka, Emiko

    1997-01-01

    A study investigated the role of touch in the use of facilitated communication with Japanese individuals with autism. Five experiments were conducted involving a "telepathy game" using a rod with an attached strain gauge. Results found the facilitator's contact controlled the motor responses of the subjects. (Author/CR)

  6. Caring and Sharing: Becoming a Peer Facilitator.

    ERIC Educational Resources Information Center

    Myrick, Robert D.; Erney, Tom

    This book contains information and skill-building activities designed to train adolescents as peer facilitators. The first chapter describes peer facilitation and provides an overview of the book. The second chapter discusses principles, concepts, and ideas to help better understand how people learn, make decisions, change, and develop their own…

  7. Facilitated Communication: The Clinical and Social Phenomenon.

    ERIC Educational Resources Information Center

    Shane, Howard C., Ed.

    This text explains the phenomenon of facilitated communication (FC) from an empirical, data-based, and/or clinical perspective. It is not a how-to-facilitate text, but one that explores the clinical and sociological reality of FC. A common theme running through each of the papers in the book is the question of FC's legitimacy. The papers reveal…

  8. Interaction Patterns and Facilitation of Peer Learning.

    ERIC Educational Resources Information Center

    Shaw, Marvin E.; And Others

    1979-01-01

    Data show that giving information to members of a group is more important in determining the perception by others that the person is facilitating group performance. Asking for information and opinions is more important in actual facilitation of group learning. Social-emotional support becomes important after initial phases of group interaction.…

  9. 49 CFR 38.2 - Equivalent facilitation.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 1 2011-10-01 2011-10-01 false Equivalent facilitation. 38.2 Section 38.2 Transportation Office of the Secretary of Transportation AMERICANS WITH DISABILITIES ACT (ADA) ACCESSIBILITY SPECIFICATIONS FOR TRANSPORTATION VEHICLES General § 38.2 Equivalent facilitation. Departures from...

  10. 49 CFR 38.2 - Equivalent facilitation.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 1 2013-10-01 2013-10-01 false Equivalent facilitation. 38.2 Section 38.2 Transportation Office of the Secretary of Transportation AMERICANS WITH DISABILITIES ACT (ADA) ACCESSIBILITY SPECIFICATIONS FOR TRANSPORTATION VEHICLES General § 38.2 Equivalent facilitation. Departures from...

  11. 49 CFR 38.2 - Equivalent facilitation.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 1 2014-10-01 2014-10-01 false Equivalent facilitation. 38.2 Section 38.2 Transportation Office of the Secretary of Transportation AMERICANS WITH DISABILITIES ACT (ADA) ACCESSIBILITY SPECIFICATIONS FOR TRANSPORTATION VEHICLES General § 38.2 Equivalent facilitation. Departures from...

  12. 49 CFR 38.2 - Equivalent facilitation.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 1 2012-10-01 2012-10-01 false Equivalent facilitation. 38.2 Section 38.2 Transportation Office of the Secretary of Transportation AMERICANS WITH DISABILITIES ACT (ADA) ACCESSIBILITY SPECIFICATIONS FOR TRANSPORTATION VEHICLES General § 38.2 Equivalent facilitation. Departures from...

  13. A Dialogic Approach to Online Facilitation

    ERIC Educational Resources Information Center

    Swann, Jennie

    2010-01-01

    Social construction of understanding has long been a significant underlying principle of learning and teaching, and while there are many models for the design of online activities to promote this, there are considerably fewer models for the facilitation of such dialogue. This paper examines some of these facilitation models from the point of view…

  14. Getting the Words Out: Facilitated Communication Training.

    ERIC Educational Resources Information Center

    Crossley, Rosemary; Remington-Gurney, Jane

    1992-01-01

    This paper discusses the use of facilitated communication training with individuals labeled as intellectually impaired, including individuals diagnosed as autistic, at the DEAL Communication Centre in Victoria, Australia. The paper describes the clients, hand use problems addressed by facilitation, literacy, structuring success, fading support,…

  15. "Stepping Up": A Focus on Facilitator Development

    ERIC Educational Resources Information Center

    Kostouros, Patricia; Warthe, D. Gaye; Carter-Snell, Catherine; Burnett, Che

    2016-01-01

    This article examines the impact on peer facilitators in "Stepping Up," a dating violence prevention program at a Canadian university. A focus group held eight months following the delivery of the program determined the personal impact of involvement in the program. Results indicate that peer facilitators experienced personal growth as…

  16. 49 CFR 38.2 - Equivalent facilitation.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false Equivalent facilitation. 38.2 Section 38.2 Transportation Office of the Secretary of Transportation AMERICANS WITH DISABILITIES ACT (ADA) ACCESSIBILITY SPECIFICATIONS FOR TRANSPORTATION VEHICLES General § 38.2 Equivalent facilitation. Departures from...

  17. Facilitator Talk in EAP Reading Classes

    ERIC Educational Resources Information Center

    Wilson, Kate

    2008-01-01

    Current sociocultural perspectives on language learning call on teachers to reinvent themselves in ways which facilitate student learning rather than transmit knowledge. For teachers, this means adopting new roles, and acquiring a new repertoire of teacher talk. This paper aims to further the work on facilitator talk begun by Clifton (2006) and…

  18. Toward Facilitative Mentoring and Catalytic Interventions

    ERIC Educational Resources Information Center

    Smith, Melissa K.; Lewis, Marilyn

    2015-01-01

    In TESOL teacher mentoring, giving advice can be conceptualized as a continuum, ranging from directive to facilitative feedback. The goal, over time, is to lead toward the facilitative end of the continuum and specifically to catalytic interventions that encourage self-reflection and autonomous learning. This study begins by examining research on…

  19. Facilitative Leadership: How Principals Lead without Dominating.

    ERIC Educational Resources Information Center

    Conley, David T.; Goldman, Paul

    1994-01-01

    "Facilitative leadership" may be defined as the ability of principals to lead without controlling, while making it easier for all members of the school community to achieve agreed-upon goals. The bulk of the Bulletin consists of a discussion of 10 propositions related to facilitative leadership drawn from 3 sources: (1) studies in…

  20. The Limited Facilitative Effect of Typographical Signals.

    ERIC Educational Resources Information Center

    Golding, Jonathan M.; Fowler, Susan B.

    1992-01-01

    Two experiments with 188 college students investigated the facilitative effect of typographical signals such as underlining, headings, or other devices to help readers identify specific points. Results do not support a general facilitative effect of typographical signals but suggest that use of signals depends on the reader's strategic processing.…

  1. Gabor domain optical coherence microscopy

    NASA Astrophysics Data System (ADS)

    Murali, Supraja

    to this technology all of which have been demonstrated in full functional hardware conceived and built during the course of this research. First, it has been demonstrated that the coherence gate created by the femtosecond laser can be coupled into a scanning optical microscope using optical design methods to include liquid lens technology that enables scanning below the surface of skin with no moving parts and at high resolution throughout a 2x2x2 mm imaging cube. Second, the integration the variable-focus liquid lens technology within a fixed-optics microscope custom optical design helped increase the working NA by an order of magnitude over the limitation imposed by the liquid lens alone. Thus, this design has enabled homogenous axial and lateral resolution at the micron-level (i.e., 2 mum) while imaging in the spectral domain, and still maintaining in vivo speeds. The latest images in biological specimens clearly demonstrate sub-cellular resolution in all dimensions throughout the imaging volume. Third, this new modality for data collection has been integrated with an automated Gabor domain image registration and fusion algorithm to provide full resolution images across the data cube in real-time. We refer to this overall OCM method as Gabor domain OCM (GD-OCM). These advantages place GD-OCM in a unique position with respect to the diagnosis of cancer, because when fully developed, it promises to enable fast and accurate screening for early symptoms that could lead to prevention. The next step for this technology is to apply it directly, in a clinical environment. This step is underway and is expected to be reported by the next generation of researchers within this group.

  2. 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.

  3. Integrating knowledge across domains to advance the science of health behavior: overcoming challenges and facilitating success.

    PubMed

    Klein, William M P; Grenen, Emily G; O'Connell, Mary; Blanch-Hartigan, Danielle; Chou, Wen-Ying Sylvia; Hall, Kara L; Taber, Jennifer M; Vogel, Amanda L

    2017-03-01

    Health behaviors often co-occur and have common determinants at multiple levels (e.g., individual, relational, environmental). Nevertheless, research programs often examine single health behaviors without a systematic attempt to integrate knowledge across behaviors. This paper highlights the significant potential of cross-cutting behavioral research to advance our understanding of the mechanisms and causal factors that shape health behaviors. It also offers suggestions for how researchers could develop more effective interventions. We highlight barriers to such an integrative science along with potential steps that can be taken to address these barriers. With a more nuanced understanding of health behavior, redundancies in research can be minimized, and a stronger evidence base for the development of health behavior interventions can be realized.

  4. Optimal domain decomposition strategies

    NASA Technical Reports Server (NTRS)

    Yoon, Yonghyun; Soni, Bharat K.

    1995-01-01

    The primary interest of the authors is in the area of grid generation, in particular, optimal domain decomposition about realistic configurations. A grid generation procedure with optimal blocking strategies has been developed to generate multi-block grids for a circular-to-rectangular transition duct. The focus of this study is the domain decomposition which optimizes solution algorithm/block compatibility based on geometrical complexities as well as the physical characteristics of flow field. The progress realized in this study is summarized in this paper.

  5. Facilitated versus Non-Facilitated Online Case Discussions: Comparing Differences in Problem Space Coverage

    ERIC Educational Resources Information Center

    Ertmer, Peggy A.; Koehler, Adrie A.

    2015-01-01

    The facilitator plays a key role in guiding students' efforts during case discussions. However, few studies have compared differences in learning outcomes for students participating in facilitated versus non-facilitated discussions. In this research, we used "problem space coverage" as a learning measure to compare outcomes between…

  6. Facilitating normative judgments of conditional probability: frequency or nested sets?

    PubMed

    Yamagishi, Kimihiko

    2003-01-01

    Recent probability judgment research contrasts two opposing views. Some theorists have emphasized the role of frequency representations in facilitating probabilistic correctness; opponents have noted that visualizing the probabilistic structure of the task sufficiently facilitates normative reasoning. In the current experiment, the following conditional probability task, an isomorph of the "Problem of Three Prisoners" was tested. "A factory manufactures artificial gemstones. Each gemstone has a 1/3 chance of being blurred, a 1/3 chance of being cracked, and a 1/3 chance of being clear. An inspection machine removes all cracked gemstones, and retains all clear gemstones. However, the machine removes 1/2 of the blurred gemstones. What is the chance that a gemstone is blurred after the inspection?" A 2 x 2 design was administered. The first variable was the use of frequency instruction. The second manipulation was the use of a roulette-wheel diagram that illustrated a "nested-sets" relationship between the prior and the posterior probabilities. Results from two experiments showed that frequency alone had modest effects, while the nested-sets instruction achieved a superior facilitation of normative reasoning. The third experiment compared the roulette-wheel diagram to tree diagrams that also showed the nested-sets relationship. The roulette-wheel diagram outperformed the tree diagrams in facilitation of probabilistic reasoning. Implications for understanding the nature of intuitive probability judgments are discussed.

  7. Cellulose binding domain proteins

    SciTech Connect

    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.

  8. The Domains of TESOL.

    ERIC Educational Resources Information Center

    Robinett, Betty Wallace

    The domains of Teachers of English to Speakers of Other Languages (TESOL) are those spheres of concern involving persons who speak languages other than English or dialects of English other than the standard. This clientele has been classified traditionally in terms of programs in English as a foreign language, English as a second language, English…

  9. 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.

  10. Domain Validity and Generalizability

    ERIC Educational Resources Information Center

    Kaiser, Henry F.; Michael, William B.

    1975-01-01

    An alternative derivation of Tryon's basic formula for the coefficient of domain validity or the coefficient of generalizability developed by Cronbach, Rajaratnam, and Glaser is provided. This derivation, which is also the generalized Kuder-Richardson coefficient, requires a relatively minimal number of assumptions compared with that in previously…

  11. 31 CFR 537.205 - Prohibited facilitation.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... the United States. (b) With respect to new investment in Burma, the prohibition against facilitation... may be waived by the President upon the making of certain determinations and notification to...

  12. Suicide: Issues of Prevention, Intervention, and Facilitation.

    ERIC Educational Resources Information Center

    Nelson, Franklyn L.

    1984-01-01

    Discusses the concept of suicide intervention which allows for the possibility of death facilitation as well as prevention. A proposed suicide intervention model is contrasted with the goals and methods of existing suicide prevention and crisis counseling services. (JAC)

  13. Dream Deprivation and Facilitation with Hypnosis

    ERIC Educational Resources Information Center

    Albert, Ira B.; Boone, Donald

    1975-01-01

    The present study attempted to deprive human subjects of dreaming through the administration of a posthypnotic suggestion and to increase or facilitate dreaming through a second suggestion that was used with another group of subjects. (Author/RK)

  14. Facilitating LOS Debriefings: A Training Manual

    NASA Technical Reports Server (NTRS)

    McDonnell, Lori K.; Jobe, Kimberly K.; Dismukes, R. Key

    1997-01-01

    This manual is a practical guide to help airline instructors effectively facilitate debriefings of Line Oriented Simulations (LOS). It is based on a recently completed study of Line Oriented Flight Training (LOFT) debriefings at several U.S. airlines. This manual presents specific facilitation tools instructors can use to achieve debriefing objectives. The approach of the manual is to be flexible so it can be tailored to the individual needs of each airline. Part One clarifies the purpose and objectives of facilitation in the LOS setting. Part Two provides recommendations for clarifying roles and expectations and presents a model for organizing discussion. Part Tree suggests techniques for eliciting active crew participation and in-depth analysis and evaluation. Finally, in Part Four, these techniques are organized according to the facilitation model. Examples of how to effectively use the techniques are provided throughout, including strategies to try when the debriefing objectives are not being fully achieved.

  15. Facilitating Transfer in College Reading Programs.

    ERIC Educational Resources Information Center

    Nist, Sherrie; Simpson, Michele L.

    1987-01-01

    Gives three activities--journal writing, microteaching partners, and the PLAE model (planning, listing, activating, and evaluating)--that can facilitate learner independence and transfer of efficient and effective study strategies in college developmental reading programs. (NKA)

  16. The Dynamics and Evolutionary Potential of Domain Loss and Emergence

    PubMed Central

    Moore, Andrew D.; Bornberg-Bauer, Erich

    2012-01-01

    The wealth of available genomic data presents an unrivaled opportunity to study the molecular basis of evolution. Studies on gene family expansions and site-dependent analyses have already helped establish important insights into how proteins facilitate adaptation. However, efforts to conduct full-scale cross-genomic comparisons between species are challenged by both growing amounts of data and the inherent difficulty in accurately inferring homology between deeply rooted species. Proteins, in comparison, evolve by means of domain rearrangements, a process more amenable to study given the strength of profile-based homology inference and the lower rates with which rearrangements occur. However, adapting to a constantly changing environment can require molecular modulations beyond reach of rearrangement alone. Here, we explore rates and functional implications of novel domain emergence in contrast to domain gain and loss in 20 arthropod species of the pancrustacean clade. Emerging domains are more likely disordered in structure and spread more rapidly within their genomes than established domains. Furthermore, although domain turnover occurs at lower rates than gene family turnover, we find strong evidence that the emergence of novel domains is foremost associated with environmental adaptation such as abiotic stress response. The results presented here illustrate the simplicity with which domain-based analyses can unravel key players of nature's adaptational machinery, complementing the classical site-based analyses of adaptation. PMID:22016574

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

    PubMed

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

    2016-02-27

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

  18. 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.

  19. 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

  20. Foreign language comprehension achievement: insights from the cognate facilitation effect.

    PubMed

    Casaponsa, Aina; Antón, Eneko; Pérez, Alejandro; Duñabeitia, Jon A

    2015-01-01

    Numerous studies have shown that the native language influences foreign word recognition and that this influence is modulated by the proficiency in the non-native language. Here we explored how the degree of reliance on cross-language similarity (as measured by the cognate facilitation effect) together with other domain-general cognitive factors contribute to reading comprehension achievement in a non-native language at different stages of the learning process. We tested two groups of native speakers of Spanish learning English at elementary and intermediate levels in an academic context. A regression model approach showed that domain-general cognitive skills are good predictors of second language reading achievement independently of the level of proficiency. Critically, we found that individual differences in the degree of reliance on the native language predicted foreign language reading achievement, showing a markedly different pattern between proficiency groups. At lower levels of proficiency the cognate facilitation effect was positively related with reading achievement, while this relation became negative at intermediate levels of foreign language learning. We conclude that the link between native- and foreign-language lexical representations helps participants at initial stages of the learning process, whereas it is no longer the case at intermediate levels of proficiency, when reliance on cross-language similarity is inversely related to successful non-native reading achievement. Thus, at intermediate levels of proficiency strong and direct mappings from the non-native lexical forms to semantic concepts are needed to achieve good non-native reading comprehension, in line with the premises of current models of bilingual lexico-semantic organization.

  1. Foreign language comprehension achievement: insights from the cognate facilitation effect

    PubMed Central

    Casaponsa, Aina; Antón, Eneko; Pérez, Alejandro; Duñabeitia, Jon A.

    2015-01-01

    Numerous studies have shown that the native language influences foreign word recognition and that this influence is modulated by the proficiency in the non-native language. Here we explored how the degree of reliance on cross-language similarity (as measured by the cognate facilitation effect) together with other domain-general cognitive factors contribute to reading comprehension achievement in a non-native language at different stages of the learning process. We tested two groups of native speakers of Spanish learning English at elementary and intermediate levels in an academic context. A regression model approach showed that domain-general cognitive skills are good predictors of second language reading achievement independently of the level of proficiency. Critically, we found that individual differences in the degree of reliance on the native language predicted foreign language reading achievement, showing a markedly different pattern between proficiency groups. At lower levels of proficiency the cognate facilitation effect was positively related with reading achievement, while this relation became negative at intermediate levels of foreign language learning. We conclude that the link between native- and foreign-language lexical representations helps participants at initial stages of the learning process, whereas it is no longer the case at intermediate levels of proficiency, when reliance on cross-language similarity is inversely related to successful non-native reading achievement. Thus, at intermediate levels of proficiency strong and direct mappings from the non-native lexical forms to semantic concepts are needed to achieve good non-native reading comprehension, in line with the premises of current models of bilingual lexico-semantic organization. PMID:25999899

  2. Magnetic domain and domain wall in Co/Pt multilayer

    NASA Astrophysics Data System (ADS)

    Talapatra, A.; Mohanty, J.

    2016-05-01

    We report systematic micromagnetic investigation of formation of magnetic domains in perpendicularly magnetized Co/Pt multilayer with the variation in magnetic anisotropy and stack thickness. The lowering of anisotropy makes the domain wall broader and domain formation less efficient. Domain sizeincreases with increasing thickness of the stack to minimize the stray field energy.The minimization of energy of the system due to domain formation makes the M-H loop narrower whereas, lower stack thickness results in a wider loop. The magnetization reversalin this system occurs due tothe nucleation and growth of reverse domains.

  3. ECOD: an evolutionary classification of protein domains.

    PubMed

    Cheng, Hua; Schaeffer, R Dustin; Liao, Yuxing; Kinch, Lisa N; Pei, Jimin; Shi, Shuoyong; Kim, Bong-Hyun; Grishin, Nick V

    2014-12-01

    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.

  4. Divalent cations increase lipid order in erythrocytes and susceptibility to secretory phospholipase A2.

    PubMed

    Vest, Rebekah S; Gonzales, Laurie J; Permann, Seth A; Spencer, Emily; Hansen, Lee D; Judd, Allan M; Bell, John D

    2004-04-01

    Elevated concentrations of intracellular calcium in erythrocytes increase membrane order and susceptibility to secretory phospholipase A2. We hypothesize that calcium aids the formation of domains of ordered lipids within erythrocyte membranes by interacting directly with the inner leaflet of the cell membrane. The interface of these domains with regions of more fluid lipids may create an environment with weakened neighbor-neighbor interactions that would facilitate phospholipid migration into the active site of bound secretory phospholipase A2. This hypothesis was investigated by determining the effects of seven other divalent ions on erythrocyte membrane properties. Changes in membrane order were assessed with steady-state fluorescence spectroscopy and two-photon microscopy with an environment-sensitive probe, laurdan. Each ion increased apparent membrane order in model membranes and in erythrocytes when introduced with an ionophore, suggesting that direct binding to the inner face of the membrane accounts for the effects of calcium on membrane fluidity. Furthermore, the degree to which ions affected membrane properties correlated with the ionic radius and electronegativity of the ions. Lastly, erythrocytes became more susceptible to enzyme hydrolysis in the presence of elevated intracellular levels of nickel and manganese, but not magnesium. These differences appeared related to the ability of the ions to induce a transition in erythrocyte shape.

  5. Magnetic Domains in Magnetostrictive Fe-Ga Alloys

    SciTech Connect

    Q. Xing; T.A. Lograsso

    2008-11-03

    Lorentz microscopy was applied to the observation of magnetic domains in iron-gallium (Fe-Ga) alloys. Results did not show any link between the magnetic domains and the magnetostriction enhancement by Ga addition, but did reveal that the drastic decrease in magnetostriction for Fe-31.2 at. % Ga was due to the presence of large scale precipitates. Magnetic domain features did not change in the alloys of A2, D0{sub 3}, A2+D0{sub 3}, A2+B2+D0{sub 3}, and A2+fine scale precipitates. Large scale precipitates within the slow-cooled Fe-31.2 at. % Ga affected both the distribution and wall motion of magnetic domains.

  6. Sorting Nexin 9 facilitates podocin endocytosis in the injured podocyte

    PubMed Central

    Sasaki, Yu; Hidaka, Teruo; Ueno, Takashi; Akiba-Takagi, Miyuki; Trejo, Juan Alejandro Oliva; Seki, Takuto; Nagai-Hosoe, Yoshiko; Tanaka, Eriko; Horikoshi, Satoshi; Tomino, Yasuhiko; Suzuki, Yusuke; Asanuma, Katsuhiko

    2017-01-01

    The irreversibility of glomerulosclerotic changes depends on the degree of podocyte injury. We have previously demonstrated the endocytic translocation of podocin to the subcellular area in severely injured podocytes and found that this process is the primary disease trigger. Here we identified the protein sorting nexin 9 (SNX9) as a novel facilitator of podocin endocytosis in a yeast two-hybrid analysis. SNX9 is involved in clathrin-mediated endocytosis, actin rearrangement and vesicle transport regulation. Our results revealed and confirmed that SNX9 interacts with podocin exclusively through the Bin–Amphiphysin–Rvs (BAR) domain of SNX9. Immunofluorescence staining revealed the expression of SNX9 in response to podocyte adriamycin-induced injury both in vitro and in vivo. Finally, an analysis of human glomerular disease biopsy samples demonstrated strong SNX9 expression and co-localization with podocin in samples representative of severe podocyte injury, such as IgA nephropathy with poor prognosis, membranous nephropathy and focal segmental glomerulosclerosis. In conclusion, we identified SNX9 as a facilitator of podocin endocytosis in severe podocyte injury and demonstrated the expression of SNX9 in the podocytes of both nephropathy model mice and human patients with irreversible glomerular disease. PMID:28266622

  7. Sorting Nexin 9 facilitates podocin endocytosis in the injured podocyte.

    PubMed

    Sasaki, Yu; Hidaka, Teruo; Ueno, Takashi; Akiba-Takagi, Miyuki; Trejo, Juan Alejandro Oliva; Seki, Takuto; Nagai-Hosoe, Yoshiko; Tanaka, Eriko; Horikoshi, Satoshi; Tomino, Yasuhiko; Suzuki, Yusuke; Asanuma, Katsuhiko

    2017-03-07

    The irreversibility of glomerulosclerotic changes depends on the degree of podocyte injury. We have previously demonstrated the endocytic translocation of podocin to the subcellular area in severely injured podocytes and found that this process is the primary disease trigger. Here we identified the protein sorting nexin 9 (SNX9) as a novel facilitator of podocin endocytosis in a yeast two-hybrid analysis. SNX9 is involved in clathrin-mediated endocytosis, actin rearrangement and vesicle transport regulation. Our results revealed and confirmed that SNX9 interacts with podocin exclusively through the Bin-Amphiphysin-Rvs (BAR) domain of SNX9. Immunofluorescence staining revealed the expression of SNX9 in response to podocyte adriamycin-induced injury both in vitro and in vivo. Finally, an analysis of human glomerular disease biopsy samples demonstrated strong SNX9 expression and co-localization with podocin in samples representative of severe podocyte injury, such as IgA nephropathy with poor prognosis, membranous nephropathy and focal segmental glomerulosclerosis. In conclusion, we identified SNX9 as a facilitator of podocin endocytosis in severe podocyte injury and demonstrated the expression of SNX9 in the podocytes of both nephropathy model mice and human patients with irreversible glomerular disease.

  8. Facilitation as a ubiquitous driver of biodiversity.

    PubMed

    McIntire, Eliot J B; Fajardo, Alex

    2014-01-01

    Models describing the biotic drivers that create and maintain biological diversity within trophic levels have focused primarily on negative interactions (i.e. competition), leaving marginal room for positive interactions (i.e. facilitation). We show facilitation to be a ubiquitous driver of biodiversity by first noting that all species use resources and thus change the local biotic or abiotic conditions, altering the available multidimensional niches. This can cause a shift in local species composition, which can cause an increase in beta, and sometimes alpha, diversity. We show that these increases are ubiquitous across ecosystems. These positive effects on diversity occur via a broad host of disparate direct and indirect mechanisms. We identify and unify several of these facilitative mechanisms and discuss why it has been easy to underappreciate the importance of facilitation. We show that net positive effects have a long history of being considered ecologically or evolutionarily unstable, and we present recent evidence of its potential stability. Facilitation goes well beyond the common case of stress amelioration and it probably gains importance as community complexity increases. While biodiversity is, in part, created by species exploiting many niches, many niches are available to exploit only because species create them.

  9. Proton-coupled sugar transport in the prototypical major facilitator superfamily protein XylE.

    PubMed

    Wisedchaisri, Goragot; Park, Min-Sun; Iadanza, Matthew G; Zheng, Hongjin; Gonen, Tamir

    2014-08-04

    The major facilitator superfamily (MFS) is the largest collection of structurally related membrane proteins that transport a wide array of substrates. The proton-coupled sugar transporter XylE is the first member of the MFS that has been structurally characterized in multiple transporting conformations, including both the outward and inward-facing states. Here we report the crystal structure of XylE in a new inward-facing open conformation, allowing us to visualize the rocker-switch movement of the N-domain against the C-domain during the transport cycle. Using molecular dynamics simulation, and functional transport assays, we describe the movement of XylE that facilitates sugar translocation across a lipid membrane and identify the likely candidate proton-coupling residues as the conserved Asp27 and Arg133. This study addresses the structural basis for proton-coupled substrate transport and release mechanism for the sugar porter family of proteins.

  10. Facilitation: An Essential Ingredient in Online Coursework

    NASA Astrophysics Data System (ADS)

    Ristvey, J.; Bogner, D.

    2003-12-01

    Mid-continent Research for Education and Learning (McREL) partnered with the Colorado School of Mines (CSM) to offer the ESSEA Earth System Science Online Course for Middle School Teachers during the 2002-2003 school year. During the two semesters that the course was offered, we were able to retain 75% of our enrollees. We found that course facilitation was the key ingredient in retaining this large number of students-who are not only scattered across the U.S., but around the world-in a rigorous online course. In this poster session, we will share what we have learned about online facilitation as part of this course, and how this knowledge might translate into other online coursework. Online facilitation begins as soon as a student enrolls in the course. When a student registers online or at CSM, McREL receives notification and then sends course materials and e-mail and written confirmation to the enrollee within 24 hours. This sets the tone for the type of communications that students can expect during the 16-week course. McREL facilitators know how time consuming monitoring participant progress can be, but feel strongly about its importance when facilitating learners who are working in small groups and are completing independent research. Timely monitoring of discussion spaces and e-mail messages is essential to maintaining a high student-retention rate. Kearsley (2000) confirms this when he states that, "the most important role of the instructor in online classes is to ensure that there is a high degree of interactivity and participation." In the ESSEA courses, the isolation of students working independently on classroom applications and reflection is balanced with group construction of interactions and causal chains. Each step of the way facilitators use guided questioning in group discussion sessions and serve as a mentor when participants develop individualized classroom assignments, giving participants the opportunity to apply what they have learned in a

  11. The mechanism of facilitated cell membrane resealing.

    PubMed

    Togo, T; Alderton, J M; Bi, G Q; Steinhardt, R A

    1999-03-01

    Disruption of the plasma membrane evokes an exocytotic response that is required for rapid membrane resealing. We show here in Swiss 3T3 fibroblasts that a second disruption at the same site reseals more rapidly than the initial wound. This facilitated response of resealing was inhibited by both low external Ca2+ concentration and specific protein kinase C (PKC) inhibitors, bisindolylmaleimide I (BIS) and Gö-6976. In addition, activation of PKC by phorbol ester facilitated the resealing of a first wound. BIS and Gö-6976 suppressed the effect of phorbol ester on resealing rate. Fluorescent dye loss from a FM1-43 pre-labeled endocytotic compartment was used to investigate the relationship between exocytosis, resealing and the facilitation of resealing. Exocytosis of endocytotic compartments near the wounding site was correlated with successful resealing. The destaining did not occur when exocytosis and resealing were inhibited by low external Ca2+ concentration or by injected tetanus toxin. When the dye loaded cells were wounded twice, FM1-43 destaining at the second wound was less than at the first wound. Less destaining was also observed in cells pre-treated with phorbol ester, suggesting newly formed vesicles, which were FM1-43 unlabeled, were exocytosed in the resealing at repeated woundings. Facilitation was also blocked by brefeldin A (BFA), a fungal metabolite that inhibits vesicle formation at the Golgi apparatus. Lowering the temperature below 20 degrees C also blocked facilitation as expected from a block of Golgi function. BFA had no effect on the resealing rate of an initial wound. The facilitation of the resealing by phorbol ester was blocked by pre-treatment with BFA. These results suggest that at first wounding the cell used the endocytotic compartment to add membrane necessary for resealing. At a second wounding, PKC, activated by Ca2+ entry at the first wound, stimulated vesicle formation from the Golgi apparatus, resulting in more rapid resealing

  12. Factors for Effective Facilitator Training Evaluation.

    DTIC Science & Technology

    1996-09-01

    34 Journal of Personality and Social Psychology 59(6): 1216-1229( 1990 ). Hackman , J. Richard and Greg R. Oldham. Work Redesign. Reading MA: Addison...the Effect of Response Distortion On Those Validities," Journal of Applied Psychology 75: 581-595 ( 1990 ). "Introduction to Facilitator Training...4 """’. r "- " \\ <*’ -#äJ ^’i&fc^i*^’.-J litSt ... A**" ■ 4? FACTORS FOR EFFECTIVE FACILITATOR TRAINING EVALUATION THESIS Mark I

  13. Facilitated diffusion buffers noise in gene expression.

    PubMed

    Schoech, Armin P; Zabet, Nicolae Radu

    2014-09-01

    Transcription factors perform facilitated diffusion [three-dimensional (3D) diffusion in the cytosol and 1D diffusion on the DNA] when binding to their target sites to regulate gene expression. Here, we investigated the influence of this binding mechanism on the noise in gene expression. Our results showed that, for biologically relevant parameters, the binding process can be represented by a two-state Markov model and that the accelerated target finding due to facilitated diffusion leads to a reduction in both the mRNA and the protein noise.

  14. Facilitated diffusion buffers noise in gene expression

    NASA Astrophysics Data System (ADS)

    Schoech, Armin P.; Zabet, Nicolae Radu

    2014-09-01

    Transcription factors perform facilitated diffusion [three-dimensional (3D) diffusion in the cytosol and 1D diffusion on the DNA] when binding to their target sites to regulate gene expression. Here, we investigated the influence of this binding mechanism on the noise in gene expression. Our results showed that, for biologically relevant parameters, the binding process can be represented by a two-state Markov model and that the accelerated target finding due to facilitated diffusion leads to a reduction in both the mRNA and the protein noise.

  15. 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.

  16. Field Evolution of Antiferromagnetic Domains and Domain Walls

    NASA Astrophysics Data System (ADS)

    Fullerton, Eric E.; Hellwig, Olav; Berger, Andreas K.

    2003-03-01

    We have used magnetron sputtered [Co(4Å)Pt(7Å)]X Co(4Å)Ru(9Å)N multiplayer films to create artificially layered antiferromagnets. In contrast to atomic antiferromagnets our model system has an antiferromagnetic (AF) exchange energy comparable to the Zeemann energy in moderate fields and allows to fine tune the relative magnitude of the different magnetic energy terms by varying the parameters X and N. With increasing X and N we observe a transition from traditionally observed sharp AF domain walls towards AF domain walls with a finite width which consist of ferromagnetic stripes, i.e. the AF domains have zero net moment whereas the domain walls carry a finite magnetic moment. Such AF domain walls have not been observed before and are a direct consequence of balancing out exchange and Zeeman energy. We also show that such domain walls are expected from theoretical energy calculations. In this contribution we study the nature and field evolution of the AF stripe domain walls by Magnetic Force Microscopy (MFM). The surface sensitivity of MFM and the finite moment of the AF domain walls allow us to image AF domains as well as domain walls. We are showing first experiments to study the AF domain wall evolution in real space while applying an external field. O.H. was supported by the Deutsche Forschungsgemeinschaft via a Forschungsstipendium under the contract number HE 3286/1-1.

  17. Space Domain Awareness

    DTIC Science & Technology

    2012-09-01

    information required to characterize a space object. Another key parameter to be considered is the frequency of observation. This sampling rate varies...useful to define the values of these parameters that approximate the current and future state of the space domain. The current catalog and network... Parameters used in estimating data needs for SDA Current Threshold Objective βmo , βimg 0.1, 10Kb 0.1, 10Kb 0.1, 10Kb Number of Objects (Na , Np

  18. Functional Analysis of CP2-Like Domain and SAM-Like Domain in TFCP2L1, Novel Pluripotency Factor of Embryonic Stem Cells.

    PubMed

    Kim, Chang Min; Jang, Tae-Ho; Park, Hyun Ho

    2016-06-01

    TFCP2L1 is a transcription factor that facilitates establishment and maintenance of pluripotency in embryonic stem cells by forming a complex transcriptional network with other transcription factors (OCT4, SOX2, and NANOG). TFCP2L1 contains two distinct domains, the CP2-like domain at the N-terminus and the SAM-like domain at the C-terminus. In this study, we found that TFCP2L1 is hexamerized in solution via the C-terminal SAM-like domain. We also found that homo-oligomerization of SAM-like domain is dependent on the concentration of the proteins. Finally, we found that TFCP2L1 binds directly to DNA via the N-terminal CP2-like domain.

  19. The Resourceful Facilitator: Teacher Leaders Constructing Identities as Facilitators of Teacher Peer Groups

    ERIC Educational Resources Information Center

    Allen, David

    2016-01-01

    The use of teacher peer groups is a prevalent strategy for school-based professional development and instructional improvement. Facilitation of such groups is an increasingly vital dimension of teacher leadership as a component of school improvement efforts. Drawing on a qualitative study of facilitation of teacher peer groups, the article…

  20. The spatial range of peripheral collinear facilitation

    PubMed Central

    Maniglia, Marcello; Pavan, Andrea; Aedo-Jury, Felipe; Trotter, Yves

    2015-01-01

    Contrast detection thresholds for a central Gabor patch (target) can be modulated by the presence of co-oriented and collinear high contrast Gabors flankers. In foveal vision collinear facilitation can be observed for target-to-flankers relative distances beyond two times the wavelength (λ) of the Gabor’s carrier, while for shorter relative distances (<2λ) there is suppression. These modulatory influences seem to disappear after 12λ. In this study, we measured contrast detection thresholds for different spatial frequencies (1, 4 and 6 cpd) and target-to-flankers relative distances ranging from 6 to 16λ, but with collinear configurations presented in near periphery at 4° of eccentricity. Results showed that in near periphery collinear facilitation extends beyond 12λ for the higher spatial frequencies tested (4 and 6 cpd), while it decays already at 10λ for the lowest spatial frequency used (i.e., 1 cpd). In addition, we found that increasing the spatial frequency the peak of collinear facilitation shifts towards larger target-to-flankers relative distances (expressed as multiples of the stimulus wavelength), an effect never reported neither for near peripheral nor for central vision. The results suggest that the peak and the spatial extent of collinear facilitation in near periphery depend on the spatial frequency of the stimuli used. PMID:26502834

  1. Effective tactile noise facilitates visual perception.

    PubMed

    Lugo, J E; Doti, R; Faubert, J

    2012-01-01

    The fulcrum principle establishes that a subthreshold excitatory signal (entering in one sense) that is synchronous with a facilitation signal (entering in a different sense) can be increased (up to a resonant-like level) and then decreased by the energy and frequency content of the facilitating signal. As a result, the sensation of the signal changes according to the excitatory signal strength. In this context, the sensitivity transitions represent the change from subthreshold activity to a firing activity in multisensory neurons. Initially the energy of their activity (supplied by the weak signals) is not enough to be detected but when the facilitating signal enters the brain, it generates a general activation among multisensory neurons, modifying their original activity. In our opinion, the result is an integrated activation that promotes sensitivity transitions and the signals are then perceived. In other words, the activity created by the interaction of the excitatory signal (e.g., visual) and the facilitating signal (tactile noise) at some specific energy, produces the capability for a central detection of an otherwise weak signal. In this work we investigate the effect of an effective tactile noise on visual perception. Specifically we show that tactile noise is capable of decreasing luminance modulated thresholds.

  2. Infant Day Care Facilitates Preschool Social Behavior.

    ERIC Educational Resources Information Center

    Field, Tiffany; And Others

    1988-01-01

    Compared play, social, and attachment behaviors of 71 preschool children who had entered infant day care at varying ages and received varying amounts of day care. Concluded that continuous infant day care in quality centers appears to facilitate preschool social behavior and does not negatively affect attachment behavior. (NH)

  3. Facilitation and Practice in Verb Acquisition

    ERIC Educational Resources Information Center

    Keren-Portnoy, Tamar

    2006-01-01

    This paper presents a model of syntax acquisition, whose main points are as follows: Syntax is acquired in an item-based manner; early learning facilitates subsequent learning--as evidenced by the accelerating rate of new verbs entering a given structure; and mastery of syntactic knowledge is typically achieved through practice--as evidenced by…

  4. Writing To Facilitate Learning in Microbiology.

    ERIC Educational Resources Information Center

    Fisher, Linda E.

    This paper describes a microbiology course that utilizes writing to facilitate learning of complex concepts, for communicating experimental results, and as a diagnostic tool for the instructor in monitoring the students' understanding of material on an on-going basis. In-class writing assignments that summarize subject units are accompanied by a…

  5. Body Posture Facilitates Retrieval of Autobiographical Memories

    ERIC Educational Resources Information Center

    Dijkstra, Katinka; Kaschak, Michael P.; Zwaan, Rolf A.

    2007-01-01

    We assessed potential facilitation of congruent body posture on access to and retention of autobiographical memories in younger and older adults. Response times were shorter when body positions during prompted retrieval of autobiographical events were similar to the body positions in the original events than when body position was incongruent.…

  6. Using Assistive Technology To Facilitate Cooperative Learning.

    ERIC Educational Resources Information Center

    Bryant, Brian R.; Rivera, Diane Pedrotty

    This conference paper describes the cooperative learning structure; presents the elements of cooperative learning; discusses how to plan, implement, and evaluate using the cooperative learning structure; introduces assistive technology services for students with disabilities; and examines how devices and services can be used to facilitate active…

  7. Competency Based Vocational Education Workshop Facilitators Guide.

    ERIC Educational Resources Information Center

    Michigan State Univ., East Lansing. Michigan Center for Career and Technical Education.

    This workshop facilitator's guide is designed to inform professional staff about competency-based vocational education (CBVE) to help eligible persons on public assistance acquire competencies necessary for gainful employment in the following occupational areas: airline reservations and travel services; computer applications; dental care;…

  8. Plant facilitation of a belowground predator.

    PubMed

    Preisser, Evan L; Dugaw, Christopher J; Dennis, Brian; Strong, Donald R

    2006-05-01

    Interest in facilitative predator plant interactions has focused upon above-ground systems. Underground physical conditions are distinctive, however, and we provide evidence that bush lupine, Lupinus arboreus, facilitates the survival of the predatory nematode Heterorhabditis marelatus. Because H. marelatus is prone to desiccation and lupines maintain a zone of moist soil around their taproots even during dry periods, we hypothesized that dry-season nematode survival under lupines might be higher than in the surrounding grasslands. We performed field surveys and measured nematode survival in lupine and grassland rhizospheres under wet- and dry-season conditions. Nematodes survived the crucial summer period better under lupines than in grasslands; however, this advantage disappeared in wet, winter soils. Modeling the probability of nematode population extinction showed that, while even large nematode cohorts were likely to go extinct in grasslands, even small cohorts in lupine rhizospheres were likely to survive until the arrival of the next prey generation. Because this nematode predator has a strong top-down effect on lupine survival via its effect on root-boring larvae of the ghost moth Hepialus californicus, this facilitative interaction may enable a belowground trophic cascade. Similar cases of predator facilitation in seasonally stressful environments are probably common in nature.

  9. Supervisor Behaviours that Facilitate Training Transfer

    ERIC Educational Resources Information Center

    Lancaster, Sue; Di Milia, Lee; Cameron, Roslyn

    2013-01-01

    Purpose: The purpose of this paper is to describe the supervisor behaviours that employees found to be helpful and unhelpful in facilitating training transfer. The study aims to provide rich qualitative data from the employee's perspective. Design/methodology/approach: This study utilises a cross-sectional design. A case study and a qualitative…

  10. Retrieval during Learning Facilitates Subsequent Memory Encoding

    ERIC Educational Resources Information Center

    Pastotter, Bernhard; Schicker, Sabine; Niedernhuber, Julia; Bauml, Karl-Heinz T.

    2011-01-01

    In multiple-list learning, retrieval during learning has been suggested to improve recall of the single lists by enhancing list discrimination and, at test, reducing interference. Using electrophysiological, oscillatory measures of brain activity, we examined to what extent retrieval during learning facilitates list encoding. Subjects studied 5…

  11. International Collaborative Learning--The Facilitation Process.

    ERIC Educational Resources Information Center

    Clear, A. G.

    International collaborative learning is becoming more viable through a variety of Internet enabled software products. Group Support Systems appear to offer promise. But it is not well understood how to facilitate the teaching and learning process in electronic environments. If education is to involve an interactive process of collaborative inquiry…

  12. Videoconferencing: A New Opportunity to Facilitate Learning

    ERIC Educational Resources Information Center

    Mader, Cheryl; Ming, Kavin

    2015-01-01

    The use of distance learning techniques as a means of delivering instruction in higher education classrooms has become increasingly popular with the growing diversity of today's college students. Videoconferencing has been used as a tool to facilitate the simultaneous communication of individuals across varying geographic regions through the use…

  13. 36 CFR 1192.2 - Equivalent facilitation.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 36 Parks, Forests, and Public Property 3 2011-07-01 2011-07-01 false Equivalent facilitation. 1192.2 Section 1192.2 Parks, Forests, and Public Property ARCHITECTURAL AND TRANSPORTATION BARRIERS COMPLIANCE BOARD AMERICANS WITH DISABILITIES ACT (ADA) ACCESSIBILITY GUIDELINES FOR TRANSPORTATION...

  14. 36 CFR 1192.2 - Equivalent facilitation.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 36 Parks, Forests, and Public Property 3 2014-07-01 2014-07-01 false Equivalent facilitation. 1192.2 Section 1192.2 Parks, Forests, and Public Property ARCHITECTURAL AND TRANSPORTATION BARRIERS COMPLIANCE BOARD AMERICANS WITH DISABILITIES ACT (ADA) ACCESSIBILITY GUIDELINES FOR TRANSPORTATION...

  15. 36 CFR 1192.2 - Equivalent facilitation.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 36 Parks, Forests, and Public Property 3 2013-07-01 2012-07-01 true Equivalent facilitation. 1192.2 Section 1192.2 Parks, Forests, and Public Property ARCHITECTURAL AND TRANSPORTATION BARRIERS COMPLIANCE BOARD AMERICANS WITH DISABILITIES ACT (ADA) ACCESSIBILITY GUIDELINES FOR TRANSPORTATION...

  16. Questioning as Facilitating Strategies in Online Discussion

    ERIC Educational Resources Information Center

    Wang, Yu-Mei

    2014-01-01

    Facilitation of online discussions presents a challenge to online learning instructors. Unlike in face-to-face courses, students in online learning do not have physical contacts with instructors. They might view instructors as authoritarian figures and perceive instructor's comments as impersonal. This article details the author's personal…

  17. Teacher Actions to Facilitate Early Algebraic Reasoning

    ERIC Educational Resources Information Center

    Hunter, Jodie

    2015-01-01

    In recent years there has been an increased emphasis on integrating the teaching of arithmetic and algebra in primary school classrooms. This requires teachers to develop links between arithmetic and algebra and use pedagogical actions that facilitate algebraic reasoning. Drawing on findings from a classroom-based study, this paper provides an…

  18. Does Teaching Creationism Facilitate Student Autonomy?

    ERIC Educational Resources Information Center

    Warnick, Bryan R.; Fooce, C. David

    2007-01-01

    The teaching of evolution in US public schools continues to generate controversy. One argument for including creationism in science classrooms is based on the goal of facilitating student autonomy. Autonomy requires that students be exposed to significant alternatives, it is argued, and religious creation stories offer a significant alternative to…

  19. 31 CFR 537.205 - Prohibited facilitation.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 3 2012-07-01 2012-07-01 false Prohibited facilitation. 537.205 Section 537.205 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY BURMESE SANCTIONS REGULATIONS...

  20. 31 CFR 537.205 - Prohibited facilitation.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 3 2013-07-01 2013-07-01 false Prohibited facilitation. 537.205 Section 537.205 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY BURMESE SANCTIONS REGULATIONS...

  1. 31 CFR 538.206 - Prohibited facilitation.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance:Treasury 3 2013-07-01 2013-07-01 false Prohibited facilitation. 538.206 Section 538.206 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY SUDANESE SANCTIONS REGULATIONS...

  2. 31 CFR 537.205 - Prohibited facilitation.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false Prohibited facilitation. 537.205 Section 537.205 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY BURMESE SANCTIONS REGULATIONS...

  3. Generic Language Facilitates Children's Cross-Classification

    ERIC Educational Resources Information Center

    Nguyen, Simone P.; Gelman, A.

    2012-01-01

    Four studies examined the role of generic language in facilitating 4- and 5-year-old children's ability to cross-classify. Participants were asked to classify an item into a familiar (taxonomic or script) category, then cross-classify it into a novel (script or taxonomic) category with the help of a clue expressed in either generic or specific…

  4. Facilitated IEP Meetings. PHP-c90

    ERIC Educational Resources Information Center

    PACER Center, 2004

    2004-01-01

    To help special education planning teams reach agreements, the Minnesota Department of Education and the Minnesota Special Education Mediation Service (MNSEMS) provide the option of facilitated IEP meetings. This option is available for IEP (Individualized Education Program), IIIP (Individual Interagency Intervention Plan), and IFSP (Individual…

  5. Facilitating Learning Spaces in Forum Theatre

    ERIC Educational Resources Information Center

    Rae, Jan

    2013-01-01

    Purpose: The purpose of this paper is to evaluate the extent to which forum theatre interventions can support non-hierarchical approaches to learning, development and change management initiatives in organisations. Design/methodology/approach: Semi-structured interviews were carried out with theatre consultancies, actors/facilitators,…

  6. 31 CFR 542.210 - Prohibited facilitation.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false Prohibited facilitation. 542.210 Section 542.210 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY SYRIAN SANCTIONS REGULATIONS Prohibitions §...

  7. Perceived Benefits of Human Sexuality Peer Facilitators

    ERIC Educational Resources Information Center

    Butler, Scott M.; Hartzell, Rose M.; Sherwood, Catherine M.

    2008-01-01

    Peer education, facilitation, and counseling programs are commonly utilized in primary and secondary prevention programs within colleges and universities. In addition, peer-based human sexuality discussions have been used as an adjunct to traditional human sexuality pedagogic programs over the last 20 years. Whereas ample evidence suggests that…

  8. Facilitating Second Language Learning with Music

    ERIC Educational Resources Information Center

    Bae, Su-Young

    2006-01-01

    The use of music in facilitating second language (as well as first language) learning is supported by evidence that points to the musical nature of even preverbal infants. Music and language have been found to develop similarly, and researchers have noted advantages to using song in learning. The author observed her Korean 21-month-old for …

  9. How Academic Teachers Perceive and Facilitate Creativity

    ERIC Educational Resources Information Center

    Bjørner, Thomas; Kofoed, Lise Busk

    2013-01-01

    We will present a case study result from a cross-disciplinary education called Medialogy, which is taught in the Technical and Science Faculty at Aalborg University. The aim of Medialogy is to facilitate creativity within technical solutions. The intention of this paper is to answer the following: how do the Medialogy teachers perceive creativity…

  10. Prose Learning for Veterinary Educators: Facilitating Acquisition

    ERIC Educational Resources Information Center

    Harkness, John E.

    1978-01-01

    A prose text in veterinary medicine can be arranged and supplemented to facilitate efficient and effective acquisition into short-term memory. Methods include: variation in textual format; relating new information to previous knowledge and future goals; providing specific, test-relevant objectives or introductions, describing mnemonic devices; and…

  11. Dynamic Flexibility and Proprioceptive Neuromuscular Facilitation.

    ERIC Educational Resources Information Center

    Hardy, Lew; Jones, David

    1986-01-01

    Two experiments are described which investigated whether results obtained in studies of static flexibility tranfer to dynamic flexibility. In both experiments, subjects were assigned to a group receiving proprioceptive neuromuscular facilitation training, ballistic stretching technique training or a control group. Results are presented and…

  12. Guide to Resources for ESL Literacy Facilitators.

    ERIC Educational Resources Information Center

    Gaber-Katz, Elaine; Zettel, Kathryn

    This resource guide, for English-as-a-Second-Language (ESL) literacy facilitators, reviews a variety of resources for ESL literacy. The guide contains three sections. The first section cites four books that provide a theoretical context for literacy work: "Ah-Hah! A New Approach to Popular Education" (Gatt-Fly); "Approaches and Methods in Language…

  13. 50 CFR 17.107 - Facilitating enforcement.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 50 Wildlife and Fisheries 7 2011-10-01 2005-10-01 true Facilitating enforcement. 17.107 Section 17.107 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR..., provide a safe ladder, manrope, safety line and illumination of the ladder; and (4) Take such...

  14. 50 CFR 17.107 - Facilitating enforcement.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 50 Wildlife and Fisheries 8 2012-10-01 2012-10-01 false Facilitating enforcement. 17.107 Section 17.107 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR..., provide a safe ladder, manrope, safety line and illumination of the ladder; and (4) Take such...

  15. 50 CFR 17.107 - Facilitating enforcement.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 50 Wildlife and Fisheries 8 2013-10-01 2013-10-01 false Facilitating enforcement. 17.107 Section 17.107 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR..., provide a safe ladder, manrope, safety line and illumination of the ladder; and (4) Take such...

  16. 50 CFR 17.107 - Facilitating enforcement.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 50 Wildlife and Fisheries 8 2014-10-01 2013-10-01 true Facilitating enforcement. 17.107 Section 17.107 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR..., provide a safe ladder, manrope, safety line and illumination of the ladder; and (4) Take such...

  17. 50 CFR 17.107 - Facilitating enforcement.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 5 2010-10-01 2010-10-01 true Facilitating enforcement. 17.107 Section 17.107 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR..., provide a safe ladder, manrope, safety line and illumination of the ladder; and (4) Take such...

  18. Improving the Human Environment of Schools: Facilitation.

    ERIC Educational Resources Information Center

    Avis, Joan P.; Bigelow, Elizabeth D.

    This training guide and reference manual helps educational leaders learn to be facilitators in the program called "Improving the Human Environment of Schools" (IHES), a participative problem-solving method designed to improve a school's "quality of life." An introductory chapter reviews the history of IHES and outlines IHES…

  19. Facilitating International Business Communication: A Global Perspective.

    ERIC Educational Resources Information Center

    Scott, James Calvert

    This document, which is intended for business educators at all levels, outlines two approaches to facilitating international business communication by adopting a global approach in business communication and related business education courses. In the first half of the document, the following steps in implementing the separate-course approach, are…

  20. 31 CFR 538.206 - Prohibited facilitation.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 3 2011-07-01 2011-07-01 false Prohibited facilitation. 538.206 Section 538.206 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY SUDANESE SANCTIONS REGULATIONS...

  1. 31 CFR 537.205 - Prohibited facilitation.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance:Treasury 3 2011-07-01 2011-07-01 false Prohibited facilitation. 537.205 Section 537.205 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY BURMESE SANCTIONS REGULATIONS...

  2. Facilitation of Retention by White Noise

    ERIC Educational Resources Information Center

    Baumeister, Alfred A.; Kistler, Doris

    1975-01-01

    This study attempted to determine if white noise (an arousing stimulus), when presented at the time of recall, facilitates performance of second and fifth grade students, and if this effect generalizes across different kinds of learning tasks. Findings indicate that white noise produces improvements in performance in both age groups. (GO)

  3. Building Better Career Futures: Facilitator Guide.

    ERIC Educational Resources Information Center

    Bezanson, Lynne; Hopkins, Sareena

    This guide, designed to be used by facilitators of the Building Better Career Futures, a comprehensive career development program for young adults, is to be used in conjunction with the Backgrounder and the Portfolio Builder. It includes an introduction to the full program and lesson plans for all topics. Each lesson plan begins with a cover sheet…

  4. Facilitating Team Learning through Transformational Leadership

    ERIC Educational Resources Information Center

    Raes, Elisabeth; Decuyper, Stefan; Lismont, Bart; Van den Bossche, Piet; Kyndt, Eva; Demeyere, Sybille; Dochy, Filip

    2013-01-01

    This article investigates when and how teams engage in team learning behaviours (TLB). More specifically, it looks into how different leadership styles facilitate TLB by influencing the social conditions that proceed them. 498 healthcare workers from 28 nursery teams filled out a questionnaire measuring the concepts leadership style, TLB, social…

  5. The HARP domain dictates the annealing helicase activity of HARP/SMARCAL1.

    PubMed

    Ghosal, Gargi; Yuan, Jingsong; Chen, Junjie

    2011-06-01

    Mutations in HepA-related protein (HARP, or SMARCAL1) cause Schimke immunoosseous dysplasia (SIOD). HARP has ATP-dependent annealing helicase activity, which helps to stabilize stalled replication forks and facilitate DNA repair during replication. Here, we show that the conserved tandem HARP (2HP) domain dictates this annealing helicase activity. Furthermore, chimeric proteins generated by fusing the 2HP domain of HARP with the SNF2 domain of BRG1 or HELLS show annealing helicase activity in vitro and, when targeted to replication forks, mimic the functions of HARP in vivo. We propose that the HARP domain endows HARP with this ATP-driven annealing helicase activity.

  6. Facilitated communication and authorship: a systematic review.

    PubMed

    Schlosser, Ralf W; Balandin, Susan; Hemsley, Bronwyn; Iacono, Teresa; Probst, Paul; von Tetzchner, Stephen

    2014-12-01

    Facilitated Communication (FC) is a technique whereby individuals with disabilities and communication impairments allegedly select letters by typing on a keyboard while receiving physical support, emotional encouragement, and other communication supports from facilitators. The validity of FC stands or falls on the question of who is authoring the typed messages--the individual with a disability or the facilitator. The International Society for Augmentative and Alternative Communication (ISAAC) formed an Ad Hoc Committee on FC and charged this committee to synthesize the evidence base related to this question in order to develop a position statement. The purpose of this paper is to report this synthesis of the extant peer-reviewed literature on the question of authorship in FC. A multi-faceted search was conducted including electronic database searches, ancestry searches, and contacting selected authors. The authors considered synopses of systematic reviews, and systematic reviews, which were supplemented with individual studies not included in any prior reviews. Additionally, documents submitted by the membership were screened for inclusion. The evidence was classified into articles that provided (a) quantitative experimental data related to the authorship of messages, (b) quantitative descriptive data on the output generated through FC without testing of authorship, (c) qualitative descriptive data on the output generated via FC without testing of authorship, and (d) anecdotal reports in which writers shared their perspectives on FC. Only documents with quantitative experimental data were analyzed for authorship. Results indicated unequivocal evidence for facilitator control: messages generated through FC are authored by the facilitators rather than the individuals with disabilities. Hence, FC is a technique that has no validity.

  7. Knowledge management across domains

    NASA Astrophysics Data System (ADS)

    Gilfillan, Lynne G.; Haddock, Gail; Borek, Stan

    2001-02-01

    This paper presents a secure, Internet-enabled, third wave knowledge management system. TheResearchPlaceTM, that will facilitate a collaborative, strategic approach to analyzing public safety problems and developing interventions to reduce them. TheResearchPlace, currently being developed under Government and private funding for use by the National Cancer Institute, Federal agencies, and the Defense Advanced Research Project Agency, will augment Geographic Information Systems and analytical tool capabilities by providing a synergistic workspace where teams of multidisciplinary professions can manage portfolios of existing knowledge resources, locate and create new knowledge resources that are added to portfolios, and collaborate with colleagues to leverage evolving portfolios' capabilities on team missions. TheResearchPlace is currently in use by selected alpha users at selected federal sites, and by the faculty of Howard University.

  8. Swarming in bounded domains

    NASA Astrophysics Data System (ADS)

    Armbruster, Dieter; Motsch, Sébastien; Thatcher, Andrea

    2017-04-01

    The Vicsek model is a prototype for the emergence of collective motion. In free space, it is characterized by a swarm of particles all moving in the same direction. Since this dynamic does not include attraction among particles, the swarm, while aligning in velocity space, has no spatial coherence. Adding specular reflection at the boundaries generates global spatial coherence of the swarms while maintaining its velocity alignment. We investigate numerically how the geometry of the domain influences the Vicsek model using three type of geometry: a channel, a disk and a rectangle. Varying the parameters of the Vicsek model (e.g. noise levels and influence horizons), we discuss the mechanisms that generate spatial coherence and show how they create new dynamical solutions of the swarming motions in these geometries. Several observables are introduced to characterize the simulated patterns (e.g. mass profile, center of mass, connectivity of the swarm).

  9. 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

  10. Does supplementary reinforcement of stereotypy facilitate extinction?

    PubMed

    Dozier, Claudia L; Iwata, Brian A; Wilson, David M; Thomason-Sassi, Jessica L; Roscoe, Eileen M

    2013-01-01

    Results of several studies suggest that delivery of supplemental (social) reinforcement for stereotypy might facilitate its subsequent extinction. We examined this possibility with 9 subjects who engaged in stereotypy by including methodological refinements to ensure that (a) subjects' stereotypy was maintained in the absence of social consequences, (b) supplementary reinforcers were highly preferred and were shown to be reinforcers for some behavior, and (c) subjects were exposed to lengthy reinforcement and extinction conditions. In spite of these modifications, only 4 subjects' stereotypy increased when supplementary reinforcement was delivered contingent on stereotypy, and no subject's stereotypy decreased below initial baseline levels when social reinforcement was subsequently withheld. Decreases in stereotypy occurred with the implementation of noncontingent reinforcement. Thus, delivery of supplementary reinforcers either did not increase stereotypy or did not facilitate extinction of stereotypy maintained by automatic reinforcement. We discuss the practical and conceptual bases of these results with respect to our current understanding of function-based interventions.

  11. Drug-facilitated sexual assault ('date rape').

    PubMed

    Schwartz, R H; Milteer, R; LeBeau, M A

    2000-06-01

    In the past few years, drug-facilitated sexual assaults have received widespread media coverage. In addition to alcohol, the most frequently used date-rape drug, flunitrazepam (Rohypnol), a fast-acting benzodiazepine, and gamma-hydroxybutyrate (GHB) and its congeners are among the most popular drugs used for this purpose. The latter drug is easily procured at some gymnasiums, popular bars, discos, and rave clubs, as well as over the Internet. Perpetrators choose these drugs because they act rapidly, produce disinhibition and relaxation of voluntary muscles, and cause the victim to have lasting anterograde amnesia for events that occur under the influence of the drug. Alcoholic beverages potentiate the drug effects. We review several date-rape drugs, provide information on laboratory testing for them, and offer guidelines for preventing drug-facilitated sexual assault.

  12. Drug-facilitated sexual assault using tetrahydrozoline.

    PubMed

    Spiller, Henry A; Siewert, Dennis J

    2012-05-01

    Drug-facilitated sexual assault (DFSA) has been defined as the use of a chemical agent to facilitate a sexual assault. We report two cases of the use of tetrahydrozoline for DFSA. We believe this is the first report with urinary quantification of tetrahydrozoline levels postassault. Blood and urine were obtained c. 20 h postexposure in two cases of reported DFSA. Tetrahydrozoline was not detected in blood but was identified in urine in both victims. After initial identification in the urine using the 2010 update to the AAFS mass spectrometry database library, tetrahydrozoline was quantified at 114 and 150 ng/mL, respectively, using GC/MS. Two unique clinical features reported in these cases were intermittent periods of consciousness and postexposure vomiting. Use of GC/MS was successful in identifying tetrahydrozoline in the 100 ng/mL range up to 20 h postexposure. For victims with late presentation, urine may be a better sample for evaluation for tetrahydrozoline.

  13. Singing can facilitate foreign language learning.

    PubMed

    Ludke, Karen M; Ferreira, Fernanda; Overy, Katie

    2014-01-01

    This study presents the first experimental evidence that singing can facilitate short-term paired-associate phrase learning in an unfamiliar language (Hungarian). Sixty adult participants were randomly assigned to one of three "listen-and-repeat" learning conditions: speaking, rhythmic speaking, or singing. Participants in the singing condition showed superior overall performance on a collection of Hungarian language tests after a 15-min learning period, as compared with participants in the speaking and rhythmic speaking conditions. This superior performance was statistically significant (p < .05) for the two tests that required participants to recall and produce spoken Hungarian phrases. The differences in performance were not explained by potentially influencing factors such as age, gender, mood, phonological working memory ability, or musical ability and training. These results suggest that a "listen-and-sing" learning method can facilitate verbatim memory for spoken foreign language phrases.

  14. Prior expectations facilitate metacognition for perceptual decision.

    PubMed

    Sherman, M T; Seth, A K; Barrett, A B; Kanai, R

    2015-09-01

    The influential framework of 'predictive processing' suggests that prior probabilistic expectations influence, or even constitute, perceptual contents. This notion is evidenced by the facilitation of low-level perceptual processing by expectations. However, whether expectations can facilitate high-level components of perception remains unclear. We addressed this question by considering the influence of expectations on perceptual metacognition. To isolate the effects of expectation from those of attention we used a novel factorial design: expectation was manipulated by changing the probability that a Gabor target would be presented; attention was manipulated by instructing participants to perform or ignore a concurrent visual search task. We found that, independently of attention, metacognition improved when yes/no responses were congruent with expectations of target presence/absence. Results were modeled under a novel Bayesian signal detection theoretic framework which integrates bottom-up signal propagation with top-down influences, to provide a unified description of the mechanisms underlying perceptual decision and metacognition.

  15. Anticipatory coarticulation facilitates word recognition in toddlers.

    PubMed

    Mahr, Tristan; McMillan, Brianna T M; Saffran, Jenny R; Ellis Weismer, Susan; Edwards, Jan

    2015-09-01

    Children learn from their environments and their caregivers. To capitalize on learning opportunities, young children have to recognize familiar words efficiently by integrating contextual cues across word boundaries. Previous research has shown that adults can use phonetic cues from anticipatory coarticulation during word recognition. We asked whether 18-24 month-olds (n=29) used coarticulatory cues on the word "the" when recognizing the following noun. We performed a looking-while-listening eyetracking experiment to examine word recognition in neutral vs. facilitating coarticulatory conditions. Participants looked to the target image significantly sooner when the determiner contained facilitating coarticulatory cues. These results provide the first evidence that novice word-learners can take advantage of anticipatory sub-phonemic cues during word recognition.

  16. Writing reports to facilitate patent applications.

    SciTech Connect

    Libman, George H.; Doerry, Armin Walter

    2004-06-01

    Brief disclosures may often be sufficient for the filing of a Technical Advance with Sandia's Intellectual Property Center, but still be inadequate to facilitate an optimum patent application where more detail and explanation are required. Consequently, the crafting of a patent application may require considerably more additional interaction between the application preparer and the inventors. This inefficiency can be considerably mitigated if the inventors address some critical aspects of a patent application when they write a technical report.

  17. A facilitated mentoring process for engineers

    SciTech Connect

    Donald, L.; Clark, M.

    1993-11-01

    Mentoring has been occurring in organizations for many, many years through a natural pairing process of people wanting to help one another. The numerous benefits of mentoring to both the protege and the mentor are widely known. In this paper we describe a Facilitated Mentoring Pilot Program for engineers, successfully completed in June, 1993. This career development tool can help make ``Every Engineer a Leader.``

  18. 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.

  19. Top-down facilitation of visual recognition

    PubMed Central

    Bar, M.; Kassam, K. S.; Ghuman, A. S.; Boshyan, J.; Schmid, A. M.; Dale, A. M.; Hämäläinen, M. S.; Marinkovic, K.; Schacter, D. L.; Rosen, B. R.; Halgren, E.

    2006-01-01

    Cortical analysis related to visual object recognition is traditionally thought to propagate serially along a bottom-up hierarchy of ventral areas. Recent proposals gradually promote the role of top-down processing in recognition, but how such facilitation is triggered remains a puzzle. We tested a specific model, proposing that low spatial frequencies facilitate visual object recognition by initiating top-down processes projected from orbitofrontal to visual cortex. The present study combined magnetoencephalography, which has superior temporal resolution, functional magnetic resonance imaging, and a behavioral task that yields successful recognition with stimulus repetitions. Object recognition elicited differential activity that developed in the left orbitofrontal cortex 50 ms earlier than it did in recognition-related areas in the temporal cortex. This early orbitofrontal activity was directly modulated by the presence of low spatial frequencies in the image. Taken together, the dynamics we revealed provide strong support for the proposal of how top-down facilitation of object recognition is initiated, and our observations are used to derive predictions for future research. PMID:16407167

  20. Spatial part-set cuing facilitation.

    PubMed

    Kelley, Matthew R; Parasiuk, Yuri; Salgado-Benz, Jennifer; Crocco, Megan

    2016-07-01

    Cole, Reysen, and Kelley [2013. Part-set cuing facilitation for spatial information. Journal of Experimental Psychology: Learning, Memory, & Cognition, 39, 1615-1620] reported robust part-set cuing facilitation for spatial information using snap circuits (a colour-coded electronics kit designed for children to create rudimentary circuit boards). In contrast, Drinkwater, Dagnall, and Parker [2006. Effects of part-set cuing on experienced and novice chess players' reconstruction of a typical chess midgame position. Perceptual and Motor Skills, 102(3), 645-653] and Watkins, Schwartz, and Lane [1984. Does part-set cuing test for memory organization? Evidence from reconstructions of chess positions. Canadian Journal of Psychology/Revue Canadienne de Psychologie, 38(3), 498-503] showed no influence of part-set cuing for spatial information when using chess boards. One key difference between the two procedures was that the snap circuit stimuli were explicitly connected to one another, whereas chess pieces were not. Two experiments examined the effects of connection type (connected vs. unconnected) and cue type (cued vs. uncued) on memory for spatial information. Using chess boards (Experiment 1) and snap circuits (Experiment 2), part-set cuing facilitation only occurred when the stimuli were explicitly connected; there was no influence of cuing with unconnected stimuli. These results are potentially consistent with the retrieval strategy disruption hypothesis, as well as the two- and three-mechanism accounts of part-set cuing.

  1. Cognitive Fatigue Facilitates Procedural Sequence Learning

    PubMed Central

    Borragán, Guillermo; Slama, Hichem; Destrebecqz, Arnaud; Peigneux, Philippe

    2016-01-01

    Enhanced procedural learning has been evidenced in conditions where cognitive control is diminished, including hypnosis, disruption of prefrontal activity and non-optimal time of the day. Another condition depleting the availability of controlled resources is cognitive fatigue (CF). We tested the hypothesis that CF, eventually leading to diminished cognitive control, facilitates procedural sequence learning. In a two-day experiment, 23 young healthy adults were administered a serial reaction time task (SRTT) following the induction of high or low levels of CF, in a counterbalanced order. CF was induced using the Time load Dual-back (TloadDback) paradigm, a dual working memory task that allows tailoring cognitive load levels to the individual’s optimal performance capacity. In line with our hypothesis, reaction times (RT) in the SRTT were faster in the high- than in the low-level fatigue condition, and performance improvement was higher for the sequential than the motor components. Altogether, our results suggest a paradoxical, facilitating impact of CF on procedural motor sequence learning. We propose that facilitated learning in the high-level fatigue condition stems from a reduction in the cognitive resources devoted to cognitive control processes that normally oppose automatic procedural acquisition mechanisms. PMID:26973501

  2. Fluoxetine Facilitates Fear Extinction Through Amygdala Endocannabinoids

    PubMed Central

    Gunduz-Cinar, Ozge; Flynn, Shaun; Brockway, Emma; Kaugars, Katherine; Baldi, Rita; Ramikie, Teniel S; Cinar, Resat; Kunos, George; Patel, Sachin; Holmes, Andrew

    2016-01-01

    Pharmacologically elevating brain endocannabinoids (eCBs) share anxiolytic and fear extinction-facilitating properties with classical therapeutics, including the selective serotonin reuptake inhibitor, fluoxetine. There are also known functional interactions between the eCB and serotonin systems and preliminary evidence that antidepressants cause alterations in brain eCBs. However, the potential role of eCBs in mediating the facilitatory effects of fluoxetine on fear extinction has not been established. Here, to test for a possible mechanistic contribution of eCBs to fluoxetine's proextinction effects, we integrated biochemical, electrophysiological, pharmacological, and behavioral techniques, using the extinction-impaired 129S1/Sv1mJ mouse strain. Chronic fluoxetine treatment produced a significant and selective increase in levels of anandamide in the BLA, and an associated decrease in activity of the anandamide-catabolizing enzyme, fatty acid amide hydrolase. Slice electrophysiological recordings showed that fluoxetine-induced increases in anandamide were associated with the amplification of eCB-mediated tonic constraint of inhibitory, but not excitatory, transmission in the BLA. Behaviorally, chronic fluoxetine facilitated extinction retrieval in a manner that was prevented by systemic or BLA-specific blockade of CB1 receptors. In contrast to fluoxetine, citalopram treatment did not increase BLA eCBs or facilitate extinction. Taken together, these findings reveal a novel, obligatory role for amygdala eCBs in the proextinction effects of a major pharmacotherapy for trauma- and stressor-related disorders and anxiety disorders. PMID:26514583

  3. Fluoxetine Facilitates Fear Extinction Through Amygdala Endocannabinoids.

    PubMed

    Gunduz-Cinar, Ozge; Flynn, Shaun; Brockway, Emma; Kaugars, Katherine; Baldi, Rita; Ramikie, Teniel S; Cinar, Resat; Kunos, George; Patel, Sachin; Holmes, Andrew

    2016-05-01

    Pharmacologically elevating brain endocannabinoids (eCBs) share anxiolytic and fear extinction-facilitating properties with classical therapeutics, including the selective serotonin reuptake inhibitor, fluoxetine. There are also known functional interactions between the eCB and serotonin systems and preliminary evidence that antidepressants cause alterations in brain eCBs. However, the potential role of eCBs in mediating the facilitatory effects of fluoxetine on fear extinction has not been established. Here, to test for a possible mechanistic contribution of eCBs to fluoxetine's proextinction effects, we integrated biochemical, electrophysiological, pharmacological, and behavioral techniques, using the extinction-impaired 129S1/Sv1mJ mouse strain. Chronic fluoxetine treatment produced a significant and selective increase in levels of anandamide in the BLA, and an associated decrease in activity of the anandamide-catabolizing enzyme, fatty acid amide hydrolase. Slice electrophysiological recordings showed that fluoxetine-induced increases in anandamide were associated with the amplification of eCB-mediated tonic constraint of inhibitory, but not excitatory, transmission in the BLA. Behaviorally, chronic fluoxetine facilitated extinction retrieval in a manner that was prevented by systemic or BLA-specific blockade of CB1 receptors. In contrast to fluoxetine, citalopram treatment did not increase BLA eCBs or facilitate extinction. Taken together, these findings reveal a novel, obligatory role for amygdala eCBs in the proextinction effects of a major pharmacotherapy for trauma- and stressor-related disorders and anxiety disorders.

  4. Stress at learning facilitates memory formation by regulating AMPA receptor trafficking through a glucocorticoid action.

    PubMed

    Conboy, Lisa; Sandi, Carmen

    2010-02-01

    Stress and glucocorticoids (GCs) can facilitate memory formation. However, the molecular mechanisms mediating their effects are largely unknown. Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor (AMPAR) trafficking has been implicated in the changes in synaptic strength at central glutamatergic synapses associated with memory formation. In cell cultures, corticosterone has been shown to condition the synaptic trafficking of the AMPAR GluA2 subunit. In this study, we investigated the involvement of GluA2 trafficking in the facilitation of learning by stress. Using the water maze spatial task involving different stress levels, mice trained under more stressful conditions (water at 22 degrees C) showed better learning and memory, and higher post-training corticosterone levels, than mice trained under lower stress (water at 30 degrees C). Strikingly, this facilitated learning by stress was accompanied by enhanced synaptic expression of GluA2 AMPARs that was not observed in mice trained under less stressful conditions. Interfering with GC actions by injecting the GC synthesis inhibitor, metyrapone, blocked both the memory facilitation and the enhanced GluA2 trafficking induced by stressful learning. Intracerebroventricular infusion of the peptide, pep2m, that blocks GluA2 synaptic trafficking by interfering with the interaction between N-ethylmaleimide-sensitive factor and GluA2, impaired immediate performance at learning as well as long-term memory retrieval, supporting a causal role for GluA2 trafficking in stress-induced facilitation of spatial learning and memory. Evidence for the involvement of the neural cell adhesion molecule N-cadherin in interaction with GluA2 is also provided. These findings underscore a new mechanism whereby stress can improve memory function.

  5. 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

  6. Discoidin Domain Receptor 1

    PubMed Central

    Song, Sunmi; Shackel, Nicholas A.; Wang, Xin M.; Ajami, Katerina; McCaughan, Geoffrey W.; Gorrell, Mark D.

    2011-01-01

    Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase that binds and is activated by collagens. Transcriptional profiling of cirrhosis in human liver using a DNA array and quantitative PCR detected elevated mRNA expression of DDR1 compared with that in nondiseased liver. The present study characterized DDR1 expression in cirrhotic and nondiseased human liver and examined the cellular effects of DDR1 expression. mRNA expression of all five isoforms of DDR1 was detected in human liver, whereas DDR1a demonstrated differential expression in liver with hepatitis C virus and primary biliary cirrhosis compared with nondiseased liver. In addition, immunoblot analysis detected shed fragments of DDR1 more readily in cirrhotic liver than in nondiseased liver. Inasmuch as DDR1 is subject to protease-mediated cleavage after prolonged interaction with collagen, this differential expression may indicate more intense activation of DDR1 protein in cirrhotic compared with nondiseased liver. In situ hybridization and immunofluorescence localized intense DDR1 mRNA and protein expression to epithelial cells including hepatocytes at the portal-parenchymal interface and the luminal aspect of the biliary epithelium. Overexpression of DDR1a altered hepatocyte behavior including increased adhesion and less migration on extracelular matrix substrates. DDR1a regulated extracellular expression of matrix metalloproteinases 1 and 2. These data elucidate DDR1 function pertinent to cirrhosis and indicate the importance of epithelial cell–collagen interactions in chronic liver injury. PMID:21356365

  7. 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

  8. The role of sulfatide lipid domains in the membrane pore-forming activity of cobra cardiotoxin.

    PubMed

    Wu, Po-Long; Chiu, Chang-Ru; Huang, Wei-Ning; Wu, Wen-Guey

    2012-05-01

    Cobra CTX A3, the major cardiotoxin (CTX) from Naja atra, is a cytotoxic, basic β-sheet polypeptide that is known to induce a transient membrane leakage of cardiomyocytes through a sulfatide-dependent CTX membrane pore formation and internalization mechanism. The molecular specificity of CTX A3-sulfatide interaction at atomic levels has also been shown by both nuclear magnetic resonance (NMR) and X-ray diffraction techniques to reveal a role of CTX-induced sulfatide conformational changes for CTX A3 binding and dimer formation. In this study, we investigate the role of sulfatide lipid domains in CTX pore formation by various biophysical methods, including fluorescence imaging and atomic force microscopy, and suggest an important role of liquid-disordered (ld) and solid-ordered (so) phase boundary in lipid domains to facilitate the process. Fluorescence spectroscopic studies on the kinetics of membrane leakage and CTX oligomerization further reveal that, although most CTXs can oligomerize on membranes, only a small fraction of CTXs oligomerizations form leakage pores. We therefore suggest that CTX binding at the boundary between the so and so/ld phase coexistence sulfatide lipid domains could form effective pores to significantly enhance the CTX-induced membrane leakage of sulfatide-containing phosphatidylcholine vesicles. The model is consistent with our earlier observations that CTX may penetrate and lyse the bilayers into small aggregates at a lipid/protein molar ratio of about 20 in the ripple P(β)' phase of phosphatidylcholine bilayers and suggest a novel mechanism for the synergistic action of cobra secretary phospholipase A2 and CTXs.

  9. End-to-end observatory software modeling using domain specific languages

    NASA Astrophysics Data System (ADS)

    Filgueira, José M.; Bec, Matthieu; Liu, Ning; Peng, Chien; Soto, José

    2014-07-01

    The Giant Magellan Telescope (GMT) is a 25-meter extremely large telescope that is being built by an international consortium of universities and research institutions. Its software and control system is being developed using a set of Domain Specific Languages (DSL) that supports a model driven development methodology integrated with an Agile management process. This approach promotes the use of standardized models that capture the component architecture of the system, that facilitate the construction of technical specifications in a uniform way, that facilitate communication between developers and domain experts and that provide a framework to ensure the successful integration of the software subsystems developed by the GMT partner institutions.

  10. Fractional diffusion on bounded domains

    DOE PAGES

    Defterli, Ozlem; D'Elia, Marta; Du, Qiang; ...

    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.

  11. Faulty ECM signaling facilitates autoimmune lymphomagenesis.

    PubMed

    Brekken, Rolf A

    2014-01-01

    The contribution of the extracellular matrix (ECM) to the microenvironment of solid tumors is appreciated although not completely understood; however, the contribution of the ECM to the development of hematopoietic tumors has not been investigated in depth. A new study by Sangaletti and colleagues demonstrates that faulty ECM signaling can facilitate malignant lymphoproliferation in mice predisposed to autoimmunity. Similar changes in ECM construction, consistent with a loss of inhibitory ECM signaling, were identified in the transition from reactive lymphoid hyperplasia to malignant chronic lymphocytic leukemia in patients. These results reveal a critical contribution of reduced collagen signaling in lymphoma and highlight the importance of appropriate ECM construction for maintenance of tissue homeostasis.

  12. Microgravity: New opportunities to facilitate biotechnology development

    NASA Astrophysics Data System (ADS)

    Johnson, Terry; Todd, Paul; Stodieck, Louis S.

    1996-03-01

    New opportunities exist to use the microgravity environment to facilitate biotechnology development. BioServe Space Technologies Center for the Commercial Development of Space offers access to microgravity environments for companies who wish to perform research or develop products in three specific life-science fields: Biomedical and Pharmaceutical Research, Biotechnology and Bioprocessing Research, and Agricultural and Environmental Research. Examples of each include physiological testing of new pharmaceutical countermeasures against symptoms that are exaggerated in space flight, crystallization and testing of novel, precompetitive biopharmaceutical substances in a convection-free environment, and closed life-support system product development.

  13. A new 'enterocompressor' to facilitate rectal anastomosis.

    PubMed

    Barraza, R P

    1990-02-01

    A newly devised enterocompressor facilitates low rectal anastomosis in children with Hirschsprung's disease. This simple surgical instrument, composed of two semicylindrical valves, a hinge, and a regulating screw, maintains intestinal anastomoses properly placed and produces spur crushing. In addition, it is inexpensive and reusable. The enterocompressor, used in 33 primary and 15 secondary Duhamel operations, and applied to normalize intestinal transit in 10 colectomies, provided adequate anastomosis and prevented leakage of intestinal contents. This enterocompressor can be used safely in children as young as six months of age.

  14. Molecular Mechanisms of Microbially Facilitated Corrosion

    DTIC Science & Technology

    1986-10-23

    AD-A173 862 MOLECULAR MECHANISMS OF MICR38IRLLY FACILITATED 1/2 CORROSION(U) TENNESSEE UNIV K~NOXVILLE INST FOR APPLIED MICROBIOLOGY D C WHITE 23 OCT...of Tennessee 10515 Research Drive, Building # 1, Suite 300 Knoxville, Tennessee 37932-2567 N 615-675-9520 October 23, 1986 00 Dr. Eli D . Schmell ELECTE...V) Program Manager, Molecular Biology NOV 4 NO8 Code 041M - Office of Naval Research 800 North Quincy Street D Arlington, VA 22217-5000. Dear Eli

  15. Orienting attention during phonetic training facilitates learning.

    PubMed

    Pederson, Eric; Guion-Anderson, Susan

    2010-02-01

    The role of consciously directed attention toward speech input in learning has not yet been determined. Previous phonetic learning studies have manipulated acoustic signals and response feedback, but not conscious control over attentional orienting. This study tests whether directed attention facilitates learning of phonetic information. Two monolingual English-speaking groups were trained with feedback on the same auditory stimuli: Hindi words. One group was instructed to attend to the consonants and the other to the vowels. The consonant-oriented group, but not the vowel-oriented group, demonstrated post-training improvement in consonant perception, confirming a role for consciously directed attentional mechanisms during phonetic learning.

  16. Learned interval time facilitates associate memory retrieval

    PubMed Central

    van de Ven, Vincent; Kochs, Sarah; Smulders, Fren; De Weerd, Peter

    2017-01-01

    The extent to which time is represented in memory remains underinvestigated. We designed a time paired associate task (TPAT) in which participants implicitly learned cue–time–target associations between cue–target pairs and specific cue–target intervals. During subsequent memory testing, participants showed increased accuracy of identifying matching cue–target pairs if the time interval during testing matched the implicitly learned interval. A control experiment showed that participants had no explicit knowledge about the cue–time associations. We suggest that “elapsed time” can act as a temporal mnemonic associate that can facilitate retrieval of events associated in memory. PMID:28298554

  17. Flexible parasympathetic responses to sadness facilitate spontaneous affect regulation.

    PubMed

    Stange, Jonathan P; Hamilton, Jessica L; Fresco, David M; Alloy, Lauren B

    2017-03-23

    The ability of the parasympathetic nervous system to flexibly adapt to changes in environmental context is thought to serve as a physiological indicator of self-regulatory capacity, and deficits in parasympathetic flexibility appear to characterize affective disorders such as depression. However, whether parasympathetic flexibility (vagal withdrawal to emotional or environmental challenges such as sadness, and vagal augmentation during recovery from sadness) could facilitate the effectiveness of adaptive affect regulation strategies is not known. In a study of 178 undergraduate students, we evaluated whether parasympathetic flexibility in response to a sad film involving loss would enhance the effectiveness of regulatory strategies (reappraisal, distraction, and suppression) spontaneously employed to reduce negative affect during a 2-min uninstructed recovery period following the induction. Parasympathetic reactivity and recovery were indexed by fluctuations in respiratory sinus arrhythmia and high-frequency heart rate variability. Cognitive reappraisal and distraction were more effective in attenuating negative affect among individuals with more parasympathetic flexibility, particularly greater vagal augmentation during recovery, relative to individuals with less parasympathetic flexibility. In contrast, suppression was associated with less attenuation of negative affect, but only among individuals who also had less vagal withdrawal during the sad film. Alternative models provided partial support for reversed directionality, with reappraisal predicting greater parasympathetic recovery, but only when individuals also experienced greater reductions in negative affect. These results suggest that contextually appropriate parasympathetic reactivity and recovery may facilitate the success of affect regulation. Impairments in parasympathetic flexibility could confer risk for affective disorders due to attenuated capacity for effective self-regulation.

  18. 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

  19. Microbial starch-binding domain.

    PubMed

    Rodríguez-Sanoja, Romina; Oviedo, Norma; Sánchez, Sergio

    2005-06-01

    Glucosidic bonds from different non-soluble polysaccharides such as starch, cellulose and xylan are hydrolyzed by amylases, cellulases and xylanases, respectively. These enzymes are produced by microorganisms. They have a modular structure that is composed of a catalytic domain and at least one non-catalytic domain that is involved in polysaccharide binding. Starch-binding modules are present in microbial enzymes that are involved in starch metabolism; these are classified into several different families on the basis of their amino acid sequence similarities. Such binding domains promote attachment to the substrate and increase its concentration at the active site of the enzyme, which allows microorganisms to degrade non-soluble starch. Fold similarities are better conserved than sequences; nevertheless, it is possible to notice two evolutionary clusters of microbial starch-binding domains. These domains have enormous potential as tags for protein immobilization, as well as for the tailoring of enzymes that play a part in polysaccharide metabolism.

  20. Phase-domain photoacoustic sensing

    NASA Astrophysics Data System (ADS)

    Gao, Fei; Zhang, Ruochong; Feng, Xiaohua; Liu, Siyu; Ding, Ran; Kishor, Rahul; Qiu, Lei; Zheng, Yuanjin

    2017-01-01

    As one of the fastest-growing imaging modalities in recent years, photoacoustic imaging has attracted tremendous research interest for various applications including anatomical, functional, and molecular imaging. The majority of the photoacoustic imaging systems are based on the time-domain pulsed photoacoustic method, which utilizes a pulsed laser source to induce a wideband photoacoustic signal, revealing optical absorption contrast. An alternative way is the frequency-domain photoacoustic method utilizing the chirping modulation of laser intensity to achieve lower system cost. In this paper, we report another way of the photoacoustic method, called phase-domain photoacoustic sensing, which explores the phase difference between two consequent intensity-modulated laser pulse induced photoacoustic measurements to reveal the optical properties. The basic principle is introduced, modeled, and experimentally validated in this paper, which opens another potential pathway to perform photoacoustic sensing and imaging, eliminating acoustic detection variations beyond the conventional time-domain and frequency-domain photoacoustic methods.

  1. The monocyte binding domain(s) on human immunoglobulin G.

    PubMed

    Woof, J M; Nik Jaafar, M I; Jefferis, R; Burton, D R

    1984-06-01

    Monocyte binding has previously been assigned to the C gamma 3 domain of human immunoglobulin G (IgG) largely on the ability of the pFc' fragment to inhibit the monocyte-IgG interaction. This ability is markedly reduced compared to the intact parent IgG. We find this result with a conventional pFc' preparation but this preparation is found to contain trace contamination of parent IgG as demonstrated by reactivity with monoclonal antibodies directed against C gamma 2 domain and light-chain epitopes of human IgG. Extensive immunoaffinity purification of the pFc' preparation removes its inhibitory ability indicating that this originates in the trace contamination of parent IgG (or Fc). Neither of the human IgG1 paraproteins TIM, lacking the C gamma 2 domain, or SIZ, lacking the C gamma 3 domain, are found to inhibit the monocyte-IgG interaction. The hinge-deleted IgG1 Dob protein shows little or no inhibitory ability. Indirect evidence for the involvement of the C gamma 2 domain in monocyte binding is considered. We suggest finally that the site of interaction is found either on the C gamma 2 domain alone or between the C gamma 2 and C gamma 3 domains.

  2. Ultra-thin clay layers facilitate seismic slip in carbonate faults.

    PubMed

    Smeraglia, Luca; Billi, Andrea; Carminati, Eugenio; Cavallo, Andrea; Di Toro, Giulio; Spagnuolo, Elena; Zorzi, Federico

    2017-04-06

    Many earthquakes propagate up to the Earth's surface producing surface ruptures. Seismic slip propagation is facilitated by along-fault low dynamic frictional resistance, which is controlled by a number of physico-chemical lubrication mechanisms. In particular, rotary shear experiments conducted at seismic slip rates (1 ms(-1)) show that phyllosilicates can facilitate co-seismic slip along faults during earthquakes. This evidence is crucial for hazard assessment along oceanic subduction zones, where pelagic clays participate in seismic slip propagation. Conversely, the reason why, in continental domains, co-seismic slip along faults can propagate up to the Earth's surface is still poorly understood. We document the occurrence of micrometer-thick phyllosilicate-bearing layers along a carbonate-hosted seismogenic extensional fault in the central Apennines, Italy. Using friction experiments, we demonstrate that, at seismic slip rates (1 ms(-1)), similar calcite gouges with pre-existing phyllosilicate-bearing (clay content ≤3 wt.%) micro-layers weaken faster than calcite gouges or mixed calcite-phyllosilicate gouges. We thus propose that, within calcite gouge, ultra-low clay content (≤3 wt.%) localized along micrometer-thick layers can facilitate seismic slip propagation during earthquakes in continental domains, possibly enhancing surface displacement.

  3. On Certain New Methodology for Reducing Sensor and Readout Electronics Circuitry Noise in Digital Domain

    NASA Technical Reports Server (NTRS)

    Kizhner, Semion; Miko, Joseph; Bradley, Damon; Heinzen, Katherine

    2008-01-01

    NASA Hubble Space Telescope (HST) and upcoming cosmology science missions carry instruments with multiple focal planes populated with many large sensor detector arrays. These sensors are passively cooled to low temperatures for low-level light (L3) and near-infrared (NIR) signal detection, and the sensor readout electronics circuitry must perform at extremely low noise levels to enable new required science measurements. Because we are at the technological edge of enhanced performance for sensors and readout electronics circuitry, as determined by thermal noise level at given temperature in analog domain, we must find new ways of further compensating for the noise in the signal digital domain. To facilitate this new approach, state-of-the-art sensors are augmented at their array hardware boundaries by non-illuminated reference pixels, which can be used to reduce noise attributed to sensors. There are a few proposed methodologies of processing in the digital domain the information carried by reference pixels, as employed by the Hubble Space Telescope and the James Webb Space Telescope Projects. These methods involve using spatial and temporal statistical parameters derived from boundary reference pixel information to enhance the active (non-reference) pixel signals. To make a step beyond this heritage methodology, we apply the NASA-developed technology known as the Hilbert- Huang Transform Data Processing System (HHT-DPS) for reference pixel information processing and its utilization in reconfigurable hardware on-board a spaceflight instrument or post-processing on the ground. The methodology examines signal processing for a 2-D domain, in which high-variance components of the thermal noise are carried by both active and reference pixels, similar to that in processing of low-voltage differential signals and subtraction of a single analog reference pixel from all active pixels on the sensor. Heritage methods using the aforementioned statistical parameters in the

  4. Chemical input multiplicity facilitates arithmetical processing.

    PubMed

    Margulies, David; Melman, Galina; Felder, Clifford E; Arad-Yellin, Rina; Shanzer, Abraham

    2004-12-01

    We describe the design and function of a molecular logic system, by which a combinatorial recognition of the input signals is utilized to efficiently process chemically encoded information. Each chemical input can target simultaneously multiple domains on the same molecular platform, resulting in a unique combination of chemical states, each with its characteristic fluorescence output. Simple alteration of the input reagents changes the emitted logic pattern and enables it to perform different algebraic operations between two bits, solely in the fluorescence mode. This system exhibits parallelism in both its chemical inputs and light outputs.

  5. 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.

  6. Electronic health records to facilitate clinical research.

    PubMed

    Cowie, Martin R; Blomster, Juuso I; Curtis, Lesley H; Duclaux, Sylvie; Ford, Ian; Fritz, Fleur; Goldman, Samantha; Janmohamed, Salim; Kreuzer, Jörg; Leenay, Mark; Michel, Alexander; Ong, Seleen; Pell, Jill P; Southworth, Mary Ross; Stough, Wendy Gattis; Thoenes, Martin; Zannad, Faiez; Zalewski, Andrew

    2017-01-01

    Electronic health records (EHRs) provide opportunities to enhance patient care, embed performance measures in clinical practice, and facilitate clinical research. Concerns have been raised about the increasing recruitment challenges in trials, burdensome and obtrusive data collection, and uncertain generalizability of the results. Leveraging electronic health records to counterbalance these trends is an area of intense interest. The initial applications of electronic health records, as the primary data source is envisioned for observational studies, embedded pragmatic or post-marketing registry-based randomized studies, or comparative effectiveness studies. Advancing this approach to randomized clinical trials, electronic health records may potentially be used to assess study feasibility, to facilitate patient recruitment, and streamline data collection at baseline and follow-up. Ensuring data security and privacy, overcoming the challenges associated with linking diverse systems and maintaining infrastructure for repeat use of high quality data, are some of the challenges associated with using electronic health records in clinical research. Collaboration between academia, industry, regulatory bodies, policy makers, patients, and electronic health record vendors is critical for the greater use of electronic health records in clinical research. This manuscript identifies the key steps required to advance the role of electronic health records in cardiovascular clinical research.

  7. Both predictability and familiarity facilitate contour integration.

    PubMed

    Sassi, Michaël; Demeyer, Maarten; Machilsen, Bart; Putzeys, Tom; Wagemans, Johan

    2014-05-30

    Research has shown that contour detection is impaired in the visual periphery for snake-shaped Gabor contours but not for circular and elliptical contours. This discrepancy in findings could be due to differences in intrinsic shape properties, including shape closure and curvature variation, as well as to differences in stimulus predictability and familiarity. In a detection task using only circular contours, the target shape is both more familiar and more predictable to the observer compared with a detection task in which a different snake-shaped contour is presented on each trial. In this study, we investigated the effects of stimulus familiarity and predictability on contour integration by manipulating and disentangling the familiarity and predictability of snakelike stimuli. We manipulated stimulus familiarity by extensively training observers with one particular snake shape. Predictability was varied by alternating trial blocks with only a single target shape and trial blocks with multiple target shapes. Our results show that both predictability and familiarity facilitated contour integration, which constitutes novel behavioral evidence for the adaptivity of the contour integration mechanism in humans. If familiarity or predictability facilitated contour integration in the periphery specifically, this could explain the discrepant findings obtained with snake contours as compared with circles or ellipses. However, we found that their facilitatory effects did not differ between central and peripheral vision and thus cannot explain that particular discrepancy in the literature.

  8. Semaphorin signaling facilitates cleft formation in the developing salivary gland.

    PubMed

    Chung, Ling; Yang, Tsung-Lin; Huang, Hsiu-Ru; Hsu, Su-Ming; Cheng, Hwai-Jong; Huang, Pei-Hsin

    2007-08-01

    Semaphorin signaling plays integral roles in multiple developmental processes. Branching morphogenesis is one such role that has not been thoroughly explored. Here, we show in mice that functional blockage of neuropilin 1 (Npn1) inhibits cleft formation in the developing submandibular gland (SMG) cultured ex vivo. This Npn1-dependent morphogenesis is mediated by Sema3A and Sema3C in an additive manner, and can be abolished by decreasing the expression of plexin A2 or plexin D1. VEGF, another known Npn1 ligand, has no apparent effects on SMG development. FGF signaling, which also mediates SMG branching morphogenesis, acts in parallel with semaphorin signaling. Finally, in contrast to the effect of FGF signaling, we find that semaphorins do not stimulate the proliferation of SMG epithelial cells. Instead, the semaphorin signals act locally on the epithelial cells to facilitate SMG cleft formation.

  9. The nested assembly of plant facilitation networks prevents species extinctions.

    PubMed

    Verdú, Miguel; Valiente-Banuet, Alfonso

    2008-12-01

    Facilitation is a positive interaction assembling ecological communities and preserving global biodiversity. Although communities acquire emerging properties when many species interact, most of our knowledge about facilitation is based on studies between pairs of species. To understand how plant facilitation preserves biodiversity in complex ecological communities, we propose to move from the study of pairwise interactions to the network approach. We show that facilitation networks behave as mutualistic networks do, characterized by a nonrandom, nested structure of plant-plant interactions in which a few generalist nurses facilitate a large number of species while the rest of the nurses facilitate only a subset of them. Consequently, generalist nurses shape a dense and highly connected network. Interestingly, such generalist nurses are the most abundant species in the community, making facilitation-shaped communities strongly resistant to extinction, as revealed by coextinction simulations. The nested structure of facilitative networks explains why facilitation, by preventing extinction, preserves biodiversity.

  10. Domain walls riding the wave.

    SciTech Connect

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

    2010-11-01

    Recent years have witnessed a rapid proliferation of electronic gadgets around the world. These devices are used for both communication and entertainment, and it is a fact that they account for a growing portion of household energy consumption and overall world consumption of electricity. Increasing the energy efficiency of these devices could have a far greater and immediate impact than a gradual switch to renewable energy sources. The advances in the area of spintronics are therefore very important, as gadgets are mostly comprised of memory and logic elements. Recent developments in controlled manipulation of magnetic domains in ferromagnet nanostructures have opened opportunities for novel device architectures. This new class of memories and logic gates could soon power millions of consumer electronic devices. The attractiveness of using domain-wall motion in electronics is due to its inherent reliability (no mechanical moving parts), scalability (3D scalable architectures such as in racetrack memory), and nonvolatility (retains information in the absence of power). The remaining obstacles in widespread use of 'racetrack-type' elements are the speed and the energy dissipation during the manipulation of domain walls. In their recent contribution to Physical Review Letters, Oleg Tretiakov, Yang Liu, and Artem Abanov from Texas A&M University in College Station, provide a theoretical description of domain-wall motion in nanoscale ferromagnets due to the spin-polarized currents. They find exact conditions for time-dependent resonant domain-wall movement, which could speed up the motion of domain walls while minimizing Ohmic losses. Movement of domain walls in ferromagnetic nanowires can be achieved by application of external magnetic fields or by passing a spin-polarized current through the nanowire itself. On the other hand, the readout of the domain state is done by measuring the resistance of the wire. Therefore, passing current through the ferromagnetic wire is

  11. Voltage-controlled domain wall traps in ferromagnetic nanowires

    NASA Astrophysics Data System (ADS)

    Bauer, Uwe; Emori, Satoru; Beach, Geoffrey S. D.

    2013-06-01

    Electrical control of magnetism has the potential to bring about revolutionary new spintronic devices, many of which rely on efficient manipulation of magnetic domain walls in ferromagnetic nanowires. Recently, it has been shown that voltage-induced charge accumulation at a metal-oxide interface can influence domain wall motion in ultrathin metallic ferromagnets, but the effects have been relatively modest and limited to the slow, thermally activated regime. Here we show that a voltage can generate non-volatile switching of magnetic properties at the nanoscale by modulating interfacial chemistry rather than charge density. Using a solid-state ionic conductor as a gate dielectric, we generate unprecedentedly strong voltage-controlled domain wall traps that function as non-volatile, electrically programmable and switchable pinning sites. Pinning strengths of at least 650 Oe can be readily achieved, enough to bring to a standstill domain walls travelling at speeds of at least ~20 m s-1. We exploit this new magneto-ionic effect to demonstrate a prototype non-volatile memory device in which voltage-controlled domain wall traps facilitate electrical bit selection in a magnetic nanowire register.

  12. Voltage-controlled domain wall traps in ferromagnetic nanowires.

    PubMed

    Bauer, Uwe; Emori, Satoru; Beach, Geoffrey S D

    2013-06-01

    Electrical control of magnetism has the potential to bring about revolutionary new spintronic devices, many of which rely on efficient manipulation of magnetic domain walls in ferromagnetic nanowires. Recently, it has been shown that voltage-induced charge accumulation at a metal-oxide interface can influence domain wall motion in ultrathin metallic ferromagnets, but the effects have been relatively modest and limited to the slow, thermally activated regime. Here we show that a voltage can generate non-volatile switching of magnetic properties at the nanoscale by modulating interfacial chemistry rather than charge density. Using a solid-state ionic conductor as a gate dielectric, we generate unprecedentedly strong voltage-controlled domain wall traps that function as non-volatile, electrically programmable and switchable pinning sites. Pinning strengths of at least 650 Oe can be readily achieved, enough to bring to a standstill domain walls travelling at speeds of at least ~20 m s(-1). We exploit this new magneto-ionic effect to demonstrate a prototype non-volatile memory device in which voltage-controlled domain wall traps facilitate electrical bit selection in a magnetic nanowire register.

  13. Partwise cross-parameterization via nonregular convex hull domains.

    PubMed

    Wu, Huai-Yu; Pan, Chunhong; Zha, Hongbin; Yang, Qing; Ma, Songde

    2011-10-01

    In this paper, we propose a novel partwise framework for cross-parameterization between 3D mesh models. Unlike most existing methods that use regular parameterization domains, our framework uses nonregular approximation domains to build the cross-parameterization. Once the nonregular approximation domains are constructed for 3D models, different (and complex) input shapes are transformed into similar (and simple) shapes, thus facilitating the cross-parameterization process. Specifically, a novel nonregular domain, the convex hull, is adopted to build shape correspondence. We first construct convex hulls for each part of the segmented model, and then adopt our convex-hull cross-parameterization method to generate compatible meshes. Our method exploits properties of the convex hull, e.g., good approximation ability and linear convex representation for interior vertices. After building an initial cross-parameterization via convex-hull domains, we use compatible remeshing algorithms to achieve an accurate approximation of the target geometry and to ensure a complete surface matching. Experimental results show that the compatible meshes constructed are well suited for shape blending and other geometric applications.

  14. Frequency-domain multiscale quantum mechanics/electromagnetics simulation method

    SciTech Connect

    Meng, Lingyi; Yin, Zhenyu; Yam, ChiYung E-mail: ghc@everest.hku.hk; Koo, SiuKong; Chen, GuanHua E-mail: ghc@everest.hku.hk; Chen, Quan; Wong, Ngai

    2013-12-28

    A frequency-domain quantum mechanics and electromagnetics (QM/EM) method is developed. Compared with the time-domain QM/EM method [Meng et al., J. Chem. Theory Comput. 8, 1190–1199 (2012)], the newly developed frequency-domain QM/EM method could effectively capture the dynamic properties of electronic devices over a broader range of operating frequencies. The system is divided into QM and EM regions and solved in a self-consistent manner via updating the boundary conditions at the QM and EM interface. The calculated potential distributions and current densities at the interface are taken as the boundary conditions for the QM and EM calculations, respectively, which facilitate the information exchange between the QM and EM calculations and ensure that the potential, charge, and current distributions are continuous across the QM/EM interface. Via Fourier transformation, the dynamic admittance calculated from the time-domain and frequency-domain QM/EM methods is compared for a carbon nanotube based molecular device.

  15. Adapting perspectives to facilitate knowledge assimilation

    SciTech Connect

    Kelsey, R.L.; Webster, R.B.

    1998-12-31

    The notion of perspective when supported in knowledge representation can allow the representation of multiple and varying points of view, some of which may even be inconsistent with one another. In an object-based knowledge representation methodology created and used by the authors, a perspective is defined by consolidating a number of objects and a number of those objects` associated attributes and methods into a view. This view can help partition a knowledge domain into separate portions. A separate portion represents an individual`s view of the knowledge domain. Representation of multiple and varying perspectives may add to the existing knowledge as well as reveal paths to additional knowledge. A simple example is presented where perspectives are used to represent game playing strategies and levels of expertise in those strategies. Players` perspectives are adapted and changed to provide additional knowledge and insight into further game playing strategies. Results show improvement in the playing of the games. Additionally, a more complex problem for applying these techniques is introduced.

  16. Mutation of domain III and domain VI in L gene conserved domain of Nipah virus

    NASA Astrophysics Data System (ADS)

    Jalani, Siti Aishah; Ibrahim, Nazlina

    2016-11-01

    Nipah virus (NiV) is the etiologic agent responsible for the respiratory illness and causes fatal encephalitis in human. NiV L protein subunit is thought to be responsible for the majority of enzymatic activities involved in viral transcription and replication. The L protein which is the viral RNA dependent RNA polymerase has high sequence homology among negative sense RNA viruses. In negative stranded RNA viruses, based on sequence alignment six conserved domain (domain I-IV) have been determined. Each domain is separated on variable regions that suggest the structure to consist concatenated functional domain. To directly address the roles of domains III and VI, site-directed mutations were constructed by the substitution of bases at sequences 2497, 2500, 5528 and 5532. Each mutated L gene can be used in future studies to test the ability for expression on in vitro translation.

  17. 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.

  18. How Identification Facilitates Effective Learning: The Evaluation of Generic versus Localized Professionalization Training

    ERIC Educational Resources Information Center

    Bjerregaard, Kirstien; Haslam, S. Alexander; Morton, Thomas

    2016-01-01

    Worldwide, organizations are keen to ensure that they achieve a performance return from the large investment they make in employee training. This study examines the way in which workgroup identification facilitates trainees' motivation to transfer learning into workplace performance. A 2 × 2 longitudinal study evaluated the effects of a new…

  19. Protein domain connectivity and essentiality

    NASA Astrophysics Data System (ADS)

    da F. Costa, L.; Rodrigues, F. A.; Travieso, G.

    2006-10-01

    Protein-protein interactions can be properly modeled as scale-free complex networks, while the lethality of proteins has been correlated with the node degrees, therefore defining a lethality-centrality rule. In this work the authors revisit this relevant problem by focusing attention not on proteins as a whole, but on their functional domains, which are ultimately responsible for their binding potential. Four networks are considered: the original protein-protein interaction network, its randomized version, and two domain networks assuming different lethality hypotheses. By using formal statistical analysis, they show that the correlation between connectivity and essentiality is higher for domains than for proteins.

  20. Characterization of the molecular basis of group II intron RNA recognition by CRS1-CRM domains.

    PubMed

    Keren, Ido; Klipcan, Liron; Bezawork-Geleta, Ayenachew; Kolton, Max; Shaya, Felix; Ostersetzer-Biran, Oren

    2008-08-22

    CRM (chloroplast RNA splicing and ribosome maturation) is a recently recognized RNA-binding domain of ancient origin that has been retained in eukaryotic genomes only within the plant lineage. Whereas in bacteria CRM domains exist as single domain proteins involved in ribosome maturation, in plants they are found in a family of proteins that contain between one and four repeats. Several members of this family with multiple CRM domains have been shown to be required for the splicing of specific plastidic group II introns. Detailed biochemical analysis of one of these factors in maize, CRS1, demonstrated its high affinity and specific binding to the single group II intron whose splicing it facilitates, the plastid-encoded atpF intron RNA. Through its association with two intronic regions, CRS1 guides the folding of atpF intron RNA into its predicted "catalytically active" form. To understand how multiple CRM domains cooperate to achieve high affinity sequence-specific binding to RNA, we analyzed the RNA binding affinity and specificity associated with each individual CRM domain in CRS1; whereas CRM3 bound tightly to the RNA, CRM1 associated specifically with a unique region found within atpF intron domain I. CRM2, which demonstrated only low binding affinity, also seems to form specific interactions with regions localized to domains I, III, and IV. We further show that CRM domains share structural similarities and RNA binding characteristics with the well known RNA recognition motif domain.

  1. Semantic facilitation in bilingual first language acquisition.

    PubMed

    Bilson, Samuel; Yoshida, Hanako; Tran, Crystal D; Woods, Elizabeth A; Hills, Thomas T

    2015-07-01

    Bilingual first language learners face unique challenges that may influence the rate and order of early word learning relative to monolinguals. A comparison of the productive vocabularies of 435 children between the ages of 6 months and 7 years-181 of which were bilingual English learners-found that monolinguals learned both English words and all-language concepts faster than bilinguals. However, bilinguals showed an enhancement of an effect previously found in monolinguals-the preference for learning words with more associative cues. Though both monolinguals and bilinguals were best fit by a similar model of word learning, semantic network structure and growth indicated that the two groups were learning English words in a different order. Further, in comparison with a model of two-monolinguals-in-one-mind, bilinguals overproduced translational equivalents. Our results support an emergent account of bilingual first language acquisition, where learning a word in one language facilitates its acquisition in a second language.

  2. Facilitating scholarly writing in academic medicine.

    PubMed

    Pololi, Linda; Knight, Sharon; Dunn, Kathleen

    2004-01-01

    Scholarly writing is a critical skill for faculty in academic medicine; however, few faculty receive instruction in the process. We describe the experience of 18 assistant professors who participated in a writing and faculty development program which consisted of 7 monthly 75-minute sessions embedded in a Collaborative Mentoring Program (CMP). Participants identified barriers to writing, developed personal writing strategies, had time to write, and completed monthly writing contracts. Participants provided written responses to open-ended questions about the learning experience, and at the end of the program, participants identified manuscripts submitted for publication, and completed an audiotaped interview. Analysis of qualitative data using data reduction, data display, and conclusion drawing/verification showed that this writing program facilitated the knowledge, skills, and support needed to foster writing productivity. All participants completed at least 1 scholarly manuscript by the end of the CMP. The impact on participants' future academic productivity requires long-term follow-up.

  3. On facilitated oxygen diffusion in muscle tissues.

    PubMed Central

    Fletcher, J E

    1980-01-01

    The role of myoglobin in facilitated diffusion of oxygen in muscle in examined in a tissue model that utilizes a central supplying capillary and a tissue cylinder concentric with the central capillary, and that includes the nonlinear characteristics of the oxygen-hemoglobin dissociation reaction. In contrast to previous work, this model exhibits the effect of blood flow and a realistic, though ideal, tissue-capillary geometry. Solutions of the model equations are obtained by a singular-perturbation technique, and numerical results are discussed for model parameters of physiologic interest. In contrast to the findings of Murray, Rubinow, Taylor, and others, fractional order perturbation terms obtained for the "boundary-layer" regions near the supplying capillaries are quite significant in the overall interpretation of the modeling results. Some closed solutions are found for special cases, and these are contrasted with the full singular-perturbation solution. Interpretations are given for parameters of physiologic interest. PMID:7295866

  4. Facilitating critical discourse through "meaningful disagreement" online.

    PubMed

    Dalley-Hewer, Jayne; Clouder, Deanne Lynn; Jackson, Ann; Goodman, Simon; Bluteau, Patricia; Davies, Bernadette

    2012-11-01

    This paper is concerned with identifying ways of facilitating "meaningful disagreement" amongst students in interprofessional online discussion forums. It builds on previous research that identified a trend toward polite agreement and only limited evidence of disagreement in this setting. Given the suggestion that disagreement indicates a deeper level of engagement in group discussion and therefore leads to deeper learning, our aim was to critique the pedagogical approach adopted by analyzing whether we were promoting a particular interprofessional discourse amongst students that favored agreement and therefore limited potential learning. Agreement in this context has been conceptualized as a form of online interprofessional "netiquette" existing amongst participants. Findings suggest that creating an online context for critical discourse is challenging; however, the careful construction of learning outcomes, trigger material/resources and learning activities, as well as attention to students' stage of study and life experience, can provoke the desired effects.

  5. Facilitating disaster preparedness through local radio broadcasting.

    PubMed

    Romo-Murphy, Eila; James, Ross; Adams, Mike

    2011-10-01

    The 2008 Disaster Mitigation Preparedness (DMP) study took place in Aceh province, Indonesia. It sought to help develop radio programmes and messages to increase resilience to disasters. The role of radio was evaluated during and after the 2004 Asian tsunami disaster. The study team interviewed 984 tsunami survivors from nine sub-districts of Banda Aceh, and local nongovernmental organisations convened eight focus groups around the area of Aceh Besar. Six key informant interviews were held with government disaster management agencies. The DMP survey is the first of its kind to interview a representative random sample of Banda Aceh residents. It reveals the importance of community and social networks, during disaster situations, when essential communications are down. A disaster warning information system based on a multi-media approach needs to be developed. The wider community should be involved in the planning, education and training of Banda Aceh and Aceh Besar residents to facilitate appropriate personal and community survival strategies.

  6. Bat echolocation calls facilitate social communication

    PubMed Central

    Knörnschild, Mirjam; Jung, Kirsten; Nagy, Martina; Metz, Markus; Kalko, Elisabeth

    2012-01-01

    Bat echolocation is primarily used for orientation and foraging but also holds great potential for social communication. The communicative function of echolocation calls is still largely unstudied, especially in the wild. Eavesdropping on vocal signatures encoding social information in echolocation calls has not, to our knowledge, been studied in free-living bats so far. We analysed echolocation calls of the polygynous bat Saccopteryx bilineata and found pronounced vocal signatures encoding sex and individual identity. We showed experimentally that free-living males discriminate approaching male and female conspecifics solely based on their echolocation calls. Males always produced aggressive vocalizations when hearing male echolocation calls and courtship vocalizations when hearing female echolocation calls; hence, they responded with complex social vocalizations in the appropriate social context. Our study demonstrates that social information encoded in bat echolocation calls plays a crucial and hitherto underestimated role for eavesdropping conspecifics and thus facilitates social communication in a highly mobile nocturnal mammal. PMID:23034703

  7. Bat echolocation calls facilitate social communication.

    PubMed

    Knörnschild, Mirjam; Jung, Kirsten; Nagy, Martina; Metz, Markus; Kalko, Elisabeth

    2012-12-07

    Bat echolocation is primarily used for orientation and foraging but also holds great potential for social communication. The communicative function of echolocation calls is still largely unstudied, especially in the wild. Eavesdropping on vocal signatures encoding social information in echolocation calls has not, to our knowledge, been studied in free-living bats so far. We analysed echolocation calls of the polygynous bat Saccopteryx bilineata and found pronounced vocal signatures encoding sex and individual identity. We showed experimentally that free-living males discriminate approaching male and female conspecifics solely based on their echolocation calls. Males always produced aggressive vocalizations when hearing male echolocation calls and courtship vocalizations when hearing female echolocation calls; hence, they responded with complex social vocalizations in the appropriate social context. Our study demonstrates that social information encoded in bat echolocation calls plays a crucial and hitherto underestimated role for eavesdropping conspecifics and thus facilitates social communication in a highly mobile nocturnal mammal.

  8. Fertile green: green facilitates creative performance.

    PubMed

    Lichtenfeld, Stephanie; Elliot, Andrew J; Maier, Markus A; Pekrun, Reinhard

    2012-06-01

    The present research sought to extend the nascent literature on color and psychological functioning by examining whether perception of the color green facilitates creativity. In four experiments, we demonstrated that a brief glimpse of green prior to a creativity task enhances creative performance. This green effect was observed using both achromatic (white, gray) and chromatic (red, blue) contrast colors that were carefully matched on nonhue properties, and using both picture-based and word-based assessments of creativity. Participants were not aware of the purpose of the experiment, and null effects were obtained on participants' self-reported mood and positive activation. These findings indicate that green has implications beyond aesthetics and suggest the need for sustained empirical work on the functional meaning of green.

  9. Criminal poisoning: drug-facilitated sexual assault.

    PubMed

    Bechtel, Laura K; Holstege, Christopher P

    2007-05-01

    Drug-facilitated sexual assault (DFSA) is a complex and ever-prevalent problem presenting to emergency departments. Emergency personnel should consider DFSA in patients who are amnestic to the specific details of the event following a reported sexual assault. The presence of ethanol or a positive routine drug screen in a sexual assault victim does not exclude the potential of a surreptitious drug being present. In addition, a negative routine drug screen does not exclude all potential agents that are used in DFSA. This article discusses agents reported in DFSA. It is imperative for emergency personnel to clearly document the history and the presenting signs and symptoms to assist laboratory personnel to hone in and detect the correct agent used in a DFSA.

  10. Drug facilitated sexual assault--a review.

    PubMed

    Hall, J A; Moore, C B T

    2008-07-01

    This review was undertaken to identify the evolutionary process in the current understanding of allegations of drug facilitated sexual assault (DFSA), so that those who work in this field may gain a better understanding of the complexities involved in such cases. Several definitions of DFSA are provided as well as a list of intoxicating substances which have so far been incriminated in this crime. Perception and alcohol use is addressed, whilst an examination of intoxication and victim outcomes reveals disturbing but important information which needs to be centrally placed within health education campaigns with a degree of urgency. The review identifies the effects of alcohol on sexual behaviour, drinking patterns and specific quantitative research indicating very high alcohol levels in some instances. In practical terms, suggestions are made following Operation Matisse, to address prevention, early detection and easier identification of DFSA cases so that victims' needs are prioritised and appropriately addressed.

  11. Facilitating consumer access to health information.

    PubMed

    Snowdon, Anne; Schnarr, Karin; Alessi, Charles

    2014-01-01

    The lead paper from Zelmer and Hagens details the substantive evolution occurring in health information technologies that has the potential to transform the relationship between consumers, health practitioners and health systems. In this commentary, the authors suggest that Canada is experiencing a shift in consumer behaviour toward a desire to actively manage one's health and wellness that is being facilitated through the advent of health applications on mobile and online technologies platforms. The result is that Canadians are now able to create personalized health solutions based on their individual health values and goals. However, before Canadians are able to derive a personal health benefit from these rapid changes in information technology, they require and are increasingly demanding greater real-time access to their own health information to better inform decision-making, as well as interoperability between their personal health tracking systems and those of their health practitioner team.

  12. Component with inspection-facilitating features

    DOEpatents

    Marra, John J; Zombo, Paul J

    2014-02-11

    A turbine airfoil can be formed with features to facilitate measurement of its wall thickness. An outer wall of the airfoil can include an outer surface and an inner surface. The outer surface of the airfoil can have an outer inspection target surface, and the inner surface of the airfoil can have an inner inspection target surface. The inner and outer target surfaces can define substantially flat regions in surfaces that are otherwise highly contoured. The inner and outer inspection target surfaces can be substantially aligned with each other. The inner and outer target surfaces can be substantially parallel to each other. As a result of these arrangements, a highly accurate measurement of wall thickness can be obtained. In one embodiment, the outer inspection target surface can be defined by an innermost surface of a groove formed in the outer surface of the outer wall of the airfoil.

  13. Podosomes of dendritic cells facilitate antigen sampling

    PubMed Central

    Reinieren-Beeren, Inge; Cambi, Alessandra; Figdor, Carl G.; van den Bogaart, Geert

    2014-01-01

    Summary Dendritic cells sample the environment for antigens and play an important role in establishing the link between innate and acquired immunity. Dendritic cells contain mechanosensitive adhesive structures called podosomes that consist of an actin-rich core surrounded by integrins, adaptor proteins and actin network filaments. They facilitate cell migration via localized degradation of extracellular matrix. Here we show that podosomes of human dendritic cells locate to spots of low physical resistance in the substrate (soft spots) where they can evolve into protrusive structures. Pathogen recognition receptors locate to these protrusive structures where they can trigger localized antigen uptake, processing and presentation to activate T-cells. Our data demonstrate a novel role in antigen sampling for podosomes of dendritic cells. PMID:24424029

  14. Podosomes of dendritic cells facilitate antigen sampling.

    PubMed

    Baranov, Maksim V; Ter Beest, Martin; Reinieren-Beeren, Inge; Cambi, Alessandra; Figdor, Carl G; van den Bogaart, Geert

    2014-03-01

    Dendritic cells sample the environment for antigens and play an important role in establishing the link between innate and acquired immunity. Dendritic cells contain mechanosensitive adhesive structures called podosomes that consist of an actin-rich core surrounded by integrins, adaptor proteins and actin network filaments. They facilitate cell migration via localized degradation of extracellular matrix. Here, we show that podosomes of human dendritic cells locate to spots of low physical resistance in the substrate (soft spots) where they can evolve into protrusive structures. Pathogen recognition receptors locate to these protrusive structures where they can trigger localized antigen uptake, processing and presentation to activate T-cells. Our data demonstrate a novel role in antigen sampling for the podosomes of dendritic cells.

  15. BTFS: The Border Trade Facilitation System

    SciTech Connect

    Phillips, L.R.

    1999-03-18

    The author demonstrates the Border Trade Facilitation System (BTFS), an agent-based bilingual e-commerce system built to expedite the regulation, control, and execution of commercial trans-border shipments during the delivery phase. The system was built to serve maquila industries at the US/Mexican border. The BTFS uses foundation technology developed here at Sandia Laboratories' Advanced Information Systems Lab (AISL), including a distributed object substrate, a general-purpose agent development framework, dynamically generated agent-human interaction via the World-Wide Web, and a collaborative agent architecture. This technology is also the substrate for the Multi-Agent Simulation Management System (MASMAS) proposed for demonstration at this conference. The BTFS executes authenticated transactions among agents performing open trading over the Internet. With the BTFS in place, one could conduct secure international transactions from any site with an Internet connection and a web browser. The BTFS is currently being evaluated for commercialization.

  16. NIRPS - Solutions Facilitator Team Overview and Accomplishments

    NASA Technical Reports Server (NTRS)

    Brown, Thomas M., III; Childress, Rhonda

    2013-01-01

    National Institute for Rocket Propulsion Systems (NIRPS) purpose is to help preserve and align government and private rocket propulsion capabilities to meet present and future US commercial, civil, and defense needs, while providing authoritative insight and recommendations to National decisional authorities. Stewardship: Monitor and analyze the state of the industry in order to formulate and recommend National Policy options and strategies that promote a healthy industrial base and ensure best-value for the American taxpayer. Technology: Identify technology needs and recommend technology insertions by leading roadmap assessments and actively participating in program formulation activities. Solutions Facilitator/Provider: Maintain relationships and awareness across the Government, industry and academia, to align available capacity with emerging demand.

  17. Bacterial Nanowires Facilitate Extracellular Electron Transfer

    NASA Astrophysics Data System (ADS)

    Gorby, Y.

    2005-12-01

    Dissimilatory metal reducing bacteria, including Shewanella oneidensis and Geobacter sulfurreducens, produce electrically conductive nanowires that facilitate electron transfer to solid phase iron oxides. Nanowires produced by S. oneidensis strain MR-1 are functionalized by decaheme cytochromes MtrC and OmcA that are distributed along the length of the nanowires, as confirmed by immunolocalization experiments using peptide specific antibodies. Mutants lacking MtrC and OmcA produce nanowires that were poorly conductive, are unable to reduce solid phase iron oxides, and do not produce electric current in microbial fuel cells. Although less completely characterized, nanowires are also produced by organisms throughout a broad metabolic spectrum, from sulfate reducing bacteria to oxygenic, phototrophic cyanobacteria. Our research suggests that electrically conductive nanowires may be common throughout the microbial world and may serve as structures for efficient electron transfer and energy dissemination in complex communities such as microbial mats and biofilms.

  18. Histamine facilitates consolidation of fear extinction.

    PubMed

    Bonini, Juliana Sartori; Da Silva, Weber Cláudio; Da Silveira, Clarice Kras Borges; Köhler, Cristiano André; Izquierdo, Iván; Cammarota, Martín

    2011-10-01

    Non-reinforced retrieval induces memory extinction, a phenomenon characterized by a decrease in the intensity of the learned response. This attribute has been used to develop extinction-based therapies to treat anxiety and post-traumatic stress disorders. Histamine modulates memory and anxiety but its role on fear extinction has not yet been evaluated. Therefore, using male Wistar rats, we determined the effect of the intra-hippocampal administration of different histaminergic agents on the extinction of step-down inhibitory avoidance (IA), a form of aversive learning. We found that intra-CA1 infusion of histamine immediately after non-reinforced retrieval facilitated consolidation of IA extinction in a dose-dependent manner. This facilitation was mimicked by the histamine N-methyltransferase inhibitor SKF91488 and the H2 receptor agonist dimaprit, reversed by the H2 receptor antagonist ranitidine, and unaffected by the H1 antagonist pyrilamine, the H3 antagonist thioperamide and the antagonist at the NMDA receptor (NMDAR) polyamine-binding site ifenprodil. Neither the H1 agonist 2-2-pyridylethylamine nor the NMDAR polyamine-binding site agonist spermidine affected the consolidation of extinction while the H3 receptor agonist imetit hampered it. Extinction induced the phosphorylation of ERK1 in dorsal CA1 while intra-CA1 infusion of the MEK inhibitor U0126 blocked extinction of the avoidance response. The extinction-induced phosphorylation of ERK1 was enhanced by histamine and dimaprit and blocked by ranitidine administered to dorsal CA1 after non-reinforced retrieval. Taken together, our data indicate that the hippocampal histaminergic system modulates the consolidation of fear extinction through a mechanism involving the H2-dependent activation of ERK signalling.

  19. Nicotine facilitates memory consolidation in perceptual learning.

    PubMed

    Beer, Anton L; Vartak, Devavrat; Greenlee, Mark W

    2013-01-01

    Perceptual learning is a special type of non-declarative learning that involves experience-dependent plasticity in sensory cortices. The cholinergic system is known to modulate declarative learning. In particular, reduced levels or efficacy of the neurotransmitter acetylcholine were found to facilitate declarative memory consolidation. However, little is known about the role of the cholinergic system in memory consolidation of non-declarative learning. Here we compared two groups of non-smoking men who learned a visual texture discrimination task (TDT). One group received chewing tobacco containing nicotine for 1 h directly following the TDT training. The other group received a similar tasting control substance without nicotine. Electroencephalographic recordings during substance consumption showed reduced alpha activity and P300 latencies in the nicotine group compared to the control group. When re-tested on the TDT the following day, both groups responded more accurately and more rapidly than during training. These improvements were specific to the retinal location and orientation of the texture elements of the TDT suggesting that learning involved early visual cortex. A group comparison showed that learning effects were more pronounced in the nicotine group than in the control group. These findings suggest that oral consumption of nicotine enhances the efficacy of nicotinic acetylcholine receptors. Our findings further suggest that enhanced efficacy of the cholinergic system facilitates memory consolidation in perceptual learning (and possibly other types of non-declarative learning). In that regard acetylcholine seems to affect consolidation processes in perceptual learning in a different manner than in declarative learning. Alternatively, our findings might reflect dose-dependent cholinergic modulation of memory consolidation. This article is part of a Special Issue entitled 'Cognitive Enhancers'.

  20. Modeling Facilitated Contaminant Transport by Mobile Bacteria

    NASA Astrophysics Data System (ADS)

    Corapcioglu, M. Yavuz; Kim, Seunghyun

    1995-01-01

    Introduction of exogenous biocolloids such as genetically engineered bacteria in a bioremediation operation can enhance the transport of contaminants in groundwater by reducing the retardation effects. Because of their colloidal size and favorable surface conditions, bacteria are efficient contaminant carriers. In cases where contaminants have a low mobility in porous media because of their high partition with solid matrix, facilitated contaminant transport by mobile bacteria can create high contaminant fluxes. When metabolically active mobile bacteria are present in a subsurface environment, the system can be treated as consisting of three phases: water phase, bacterial phase, and stationary solid matrix phase. In this work a mathematical model based on mass balance equations is developed to describe the facilitated transport and fate of a contaminant and bacteria in a porous medium. Bacterial partition between the bulk solution and the stationary solid matrix and contaminant partition among three phases are represented by expressions in terms of measurable quantities. Solutions were obtained to provide estimates of contaminant and bacterial concentrations. A dimensional analysis of the transport model was utilized to estimate model parameters from the experimental data and to assess the effect of several parameters on model behavior. The model results matched favorably with experimental data of Jenkins and Lion (1993). The presence of mobile bacteria enhances the contaminant transport. However, bacterial consumption of the contaminant, which serves as a bacterial nutrient, can attenuate the contaminant mobility. The work presented in this paper is the first three-phase model to include the effects of substrate metabolism on the fate of groundwater contaminants.

  1. Hyaluronidase facilitated subcutaneous immunoglobulin in primary immunodeficiency

    PubMed Central

    Jolles, Stephen

    2013-01-01

    Immunoglobulin (Ig)-replacement therapy represents the mainstay of treatment for patients with primary antibody deficiency and is administered either intravenously (IVIg) or subcutaneously (SCIg). While hyaluronidase has been used in clinical practice for over 50 years, the development of a high-purity recombinant form of this enzyme (recombinant human hyaluronidase PH20) has recently enabled the study of repeated and more prolonged use of hyaluronidase in facilitating the delivery of SC medicines. It has been used in a wide range of clinical settings to give antibiotics, local anesthetics, insulin, morphine, fluid replacement, and larger molecules, such as antibodies. Hyaluronidase has been used to help overcome the limitations on the maximum volume that can be delivered into the SC space by enabling dispersion of SCIg and its absorption into lymphatics. The rate of facilitated SCIg (fSCIg) infusion is equivalent to that of IVIg, and the volume administered at a single site can be greater than 700 mL, a huge increase over conventional SCIg, at 20–40 mL. The use of fSCIg avoids the higher incidence of systemic side effects of IVIg, and it has higher bioavailability than SCIg. Data on the long-term safety of this approach are currently lacking, as fSCIg has only recently become available. fSCIg may help several areas of patient management in primary antibody deficiency, and the extent to which it may be used in future will depend on long-term safety data and cost–benefit analysis. PMID:27471693

  2. Tailoring volume magnetostriction of giant magnetostrictive materials by engineering magnetic domain morphology

    NASA Astrophysics Data System (ADS)

    Zhang, Changsheng; Ma, Tianyu; Sun, Guangai

    2017-02-01

    Volume conservation is usually considered for the classic magnetostrictive materials during technical magnetization process. The present work reports the forced volume magnetostriction prior to saturation magnetization in the rare-earth giant magnetostrictive materials by engineering the initial magnetic domain morphology. It is found that the volume magnetostriction can be manipulated with the changeable sign and magnitude from about -200 × 10-6 at the thermal-demagnetized state to 450 × 10-6 at the domain-aligned state. Such behavior arises from the different domain pathways. On the light of these observations, the exploration of materials design and applications based on the volume magnetostriction effect might be facilitated.

  3. Structure of axionic domain walls

    NASA Astrophysics Data System (ADS)

    Huang, M. C.; Sikivie, P.

    1985-09-01

    The structure of axionic domain walls is investigated using the low-energy effective theory of axions and pions. We derive the spatial dependence of the phases of the Peccei-Quinn scalar field and the QCD quark-antiquark condensates inside an axionic domain wall. Thence an accurate estimate of the wall surface energy density is obtained. The equations of motion for axions, photons, leptons, and baryons in the neighborhood of axionic domain walls are written down and estimates are given for the wall reflection and transmission coefficients of these particles. Finally, we discuss the energy dissipation by axionic domain walls oscillating in the early universe due to the reflection of particles in the primordial soup.

  4. Leading Instructional Rounds in Education: A Facilitator?'s Guide. Instructional Rounds Series

    ERIC Educational Resources Information Center

    Fowler-Finn, Thomas

    2013-01-01

    Instructional rounds is a powerful form of professional learning aimed at helping schools and systems develop the capacity to educate all children to high levels. In this practical book, Thomas Fowler-Finn, an experienced consultant who has worked closely with the Harvard team that pioneered instructional rounds, discusses how facilitators can…

  5. Facilitation in Action: The Reflective Practice of Two Facilitators Using a Participation Training Model

    ERIC Educational Resources Information Center

    Treff, Marjorie E.; Earnest, Steve

    2016-01-01

    This article describes the experiences of two graduate faculty members from Indiana University who facilitated two workshops sponsored by Ball State University at Highlander Research and Education Center, one in May of 2013, and another in May of 2014. We describe the history of Participation Training, the program we used to plan and conduct…

  6. The Role of the Facilitator on Total Quality Management Teams.

    ERIC Educational Resources Information Center

    Eakin, William L.

    1993-01-01

    As Total Quality Management teams work to improve organizational processes, several types of facilitators emerge: the director, the workhorse, and the cheerleader. Experience at the University of Kansas illustrates how different facilitator styles can affect team learning. (MSE)

  7. Unfolding the HIV-1 reverse transcriptase RNase H domain – how to lose a molecular tug-of-war

    PubMed Central

    Zheng, Xunhai; Pedersen, Lars C.; Gabel, Scott A.; Mueller, Geoffrey A.; DeRose, Eugene F.; London, Robert E.

    2016-01-01

    Formation of the mature HIV-1 reverse transcriptase (RT) p66/p51 heterodimer requires subunit-specific processing of the p66/p66′ homodimer precursor. Since the ribonuclease H (RH) domain contains an occult cleavage site located near its center, cleavage must occur either prior to folding or subsequent to unfolding. Recent NMR studies have identified a slow, subunit-specific RH domain unfolding process proposed to result from a residue tug-of-war between the polymerase and RH domains on the functionally inactive, p66′ subunit. Here, we describe a structural comparison of the isolated RH domain with a domain swapped RH dimer that reveals several intrinsically destabilizing characteristics of the isolated domain that facilitate excursions of Tyr427 from its binding pocket and separation of helices B and D. These studies provide independent support for the subunit-selective RH domain unfolding pathway in which instability of the Tyr427 binding pocket facilitates its release followed by domain transfer, acting as a trigger for further RH domain destabilization and subsequent unfolding. As further support for this pathway, NMR studies demonstrate that addition of an RH active site-directed isoquinolone ligand retards the subunit-selective RH′ domain unfolding behavior of the p66/p66′ homodimer. This study demonstrates the feasibility of directly targeting RT maturation with therapeutics. PMID:26773054

  8. Unfolding the HIV-1 reverse transcriptase RNase H domain – how to lose a molecular tug-of-war

    SciTech Connect

    Zheng, Xunhai; Pedersen, Lars C.; Gabel, Scott A.; Mueller, Geoffrey A.; DeRose, Eugene F.; London, Robert E.

    2016-01-14

    Formation of the mature HIV-1 reverse transcriptase (RT) p66/p51 heterodimer requires subunit-specific processing of the p66/p66' homodimer precursor. Since the ribonuclease H (RH) domain contains an occult cleavage site located near its center, cleavage must occur either prior to folding or subsequent to unfolding. Recent NMR studies have identified a slow, subunit-specific RH domain unfolding process proposed to result from a residue tug-of-war between the polymerase and RH domains on the functionally inactive, p66' subunit. Here, we describe a structural comparison of the isolated RH domain with a domain swapped RH dimer that reveals several intrinsically destabilizing characteristics of the isolated domain that facilitate excursions of Tyr427 from its binding pocket and separation of helices B and D. These studies provide independent support for the subunit-selective RH domain unfolding pathway in which instability of the Tyr427 binding pocket facilitates its release followed by domain transfer, acting as a trigger for further RH domain destabilization and subsequent unfolding. As further support for this pathway, NMR studies demonstrate that addition of an RH active site-directed isoquinolone ligand retards the subunit-selective RH' domain unfolding behavior of the p66/p66' homodimer. As a result, this study demonstrates the feasibility of directly targeting RT maturation with therapeutics.

  9. Unfolding the HIV-1 reverse transcriptase RNase H domain – how to lose a molecular tug-of-war

    DOE PAGES

    Zheng, Xunhai; Pedersen, Lars C.; Gabel, Scott A.; ...

    2016-01-14

    Formation of the mature HIV-1 reverse transcriptase (RT) p66/p51 heterodimer requires subunit-specific processing of the p66/p66' homodimer precursor. Since the ribonuclease H (RH) domain contains an occult cleavage site located near its center, cleavage must occur either prior to folding or subsequent to unfolding. Recent NMR studies have identified a slow, subunit-specific RH domain unfolding process proposed to result from a residue tug-of-war between the polymerase and RH domains on the functionally inactive, p66' subunit. Here, we describe a structural comparison of the isolated RH domain with a domain swapped RH dimer that reveals several intrinsically destabilizing characteristics of themore » isolated domain that facilitate excursions of Tyr427 from its binding pocket and separation of helices B and D. These studies provide independent support for the subunit-selective RH domain unfolding pathway in which instability of the Tyr427 binding pocket facilitates its release followed by domain transfer, acting as a trigger for further RH domain destabilization and subsequent unfolding. As further support for this pathway, NMR studies demonstrate that addition of an RH active site-directed isoquinolone ligand retards the subunit-selective RH' domain unfolding behavior of the p66/p66' homodimer. As a result, this study demonstrates the feasibility of directly targeting RT maturation with therapeutics.« less

  10. Engineered autonomous human variable domains

    PubMed Central

    Nilvebrant, Johan; Tessier, Peter M.; Sidhu, Sachdev S.

    2017-01-01

    The complex multi-chain architecture of antibodies has spurred interest in smaller derivatives that retain specificity but can be more easily produced in bacteria. Domain antibodies consisting of single variable domains are the smallest antibody fragments and have been shown to possess enhanced ability to target epitopes that are difficult to access using multidomain antibodies. However, in contrast to natural camelid antibody domains, human variable domains typically suffer from low stability and high propensity to aggregate. This review summarizes strategies to improve the biophysical properties of heavy chain variable domains from human antibodies with an emphasis on aggregation resistance. Several protein engineering approaches have targeted antibody frameworks and complementarity determining regions to stabilize the native state and prevent aggregation of the denatured state. Recent findings enable the construction of highly diverse libraries enriched in aggregation-resistant variants that are expected to provide binders to diverse antigens. Engineered domain antibodies possess unique advantages in expression, epitope preference and flexibility of formatting over conventional immunoreagents and are a promising class of antibody fragments for biomedical development. PMID:27655414

  11. Structure of the periplasmic adaptor protein from a major facilitator superfamily (MFS) multidrug efflux pump

    PubMed Central

    Hinchliffe, Philip; Greene, Nicholas P.; Paterson, Neil G.; Crow, Allister; Hughes, Colin; Koronakis, Vassilis

    2014-01-01

    Periplasmic adaptor proteins are key components of bacterial tripartite efflux pumps. The 2.85 Å resolution structure of an MFS (major facilitator superfamily) pump adaptor, Aquifex aeolicus EmrA, shows linearly arranged α-helical coiled-coil, lipoyl, and β-barrel domains, but lacks the fourth membrane-proximal domain shown in other pumps to interact with the inner membrane transporter. The adaptor α-hairpin, which binds outer membrane TolC, is exceptionally long at 127 Å, and the β-barrel contains a conserved disordered loop. The structure extends the view of adaptors as flexible, modular components that mediate diverse pump assembly, and suggests that in MFS tripartite pumps a hexamer of adaptors could provide a periplasmic seal. PMID:24996185

  12. Oligonucleotide facilitators may inhibit or activate a hammerhead ribozyme.

    PubMed Central

    Jankowsky, E; Schwenzer, B

    1996-01-01

    Facilitators are oligonucleotides capable of affecting hammerhead ribozyme activity by interacting with the substrate at the termini of the ribozyme. Facilitator effects were determined in vitro using a system consisting of a ribozyme with 7 nucleotides in every stem sequence and two substrates with inverted facilitator binding sequences. The effects of 9mer and 12mer RNA as well as DNA facilitators which bind either adjacent to the 3'- or 5'-end of the ribozyme were investigated. A kinetic model was developed which allows determination of the apparent dissociation constant of the ribozyme-substrate complex from single turnover reactions. We observed a decreased dissociation constant of the ribozyme-substrate complex due to facilitator addition corresponding to an additional stabilization energy of delta delta G=-1.7 kcal/mol with 3'-end facilitators. The cleavage rate constant was increased by 3'-end facilitators and decreased by 5'-end facilitators. Values for Km were slightly lowered by all facilitators and kcat was increased by 3'-end facilitators and decreased by 5'-end facilitators in our system. Generally the facilitator effects increased with the length of the facilitators and RNA provided greater effects than DNA of the same sequence. Results suggest facilitator influences on several steps of the hammerhead reaction, substrate association, cleavage and dissociation of products. Moreover, these effects are dependent in different manners on ribozyme and substrate concentration. This leads to the conclusion that there is a concentration dependence whether activation or inhibition is caused by facilitators. Conclusions are drawn with regard to the design of hammerhead ribozyme facilitator systems. PMID:8602353

  13. A Gestalt Point of View on Facilitating Growth in Counseling

    ERIC Educational Resources Information Center

    Harman, Robert L.

    1975-01-01

    If counselors are to be facilitators of client growth, it would seem essentail that they become familiar with the concept of growth and ways to facilitate it. The author defines growth from a gestalt therapy point of view and provides techniques and examples of ways to facilitate client growth. (Author)

  14. The Dynamics of Syntax Acquisition: Facilitation between Syntactic Structures

    ERIC Educational Resources Information Center

    Keren-Portnoy, Tamar; Keren, Michael

    2011-01-01

    This paper sets out to show how facilitation between different clause structures operates over time in syntax acquisition. The phenomenon of facilitation within given structures has been widely documented, yet inter-structure facilitation has rarely been reported so far. Our findings are based on the naturalistic production corpora of six toddlers…

  15. Deconstructing Inquiry in the Professional Development School: Exploring the Domains and Contents of Teachers' Questions

    ERIC Educational Resources Information Center

    Dana, Nancy Fichtman; Yendol-Hoppey, Diane; Snow-Gerono, Jennifer L.

    2006-01-01

    Having facilitated, read, and collected more than 200 teacher research pieces written by prospective and practicing teachers, the authors conducted a systematic analysis of the domains and contents of teachers' questions as they embarked on their first research study. Focusing on the questions teachers ask led to the generation of a typology of…

  16. Elongated polyproline motifs facilitate enamel evolution through matrix subunit compaction.

    PubMed

    Jin, Tianquan; Ito, Yoshihiro; Luan, Xianghong; Dangaria, Smit; Walker, Cameron; Allen, Michael; Kulkarni, Ashok; Gibson, Carolyn; Braatz, Richard; Liao, Xiubei; Diekwisch, Thomas G H

    2009-12-01

    Vertebrate body designs rely on hydroxyapatite as the principal mineral component of relatively light-weight, articulated endoskeletons and sophisticated tooth-bearing jaws, facilitating rapid movement and efficient predation. Biological mineralization and skeletal growth are frequently accomplished through proteins containing polyproline repeat elements. Through their well-defined yet mobile and flexible structure polyproline-rich proteins control mineral shape and contribute many other biological functions including Alzheimer's amyloid aggregation and prolamine plant storage. In the present study we have hypothesized that polyproline repeat proteins exert their control over biological events such as mineral growth, plaque aggregation, or viscous adhesion by altering the length of their central repeat domain, resulting in dramatic changes in supramolecular assembly dimensions. In order to test our hypothesis, we have used the vertebrate mineralization protein amelogenin as an exemplar and determined the biological effect of the four-fold increased polyproline tandem repeat length in the amphibian/mammalian transition. To study the effect of polyproline repeat length on matrix assembly, protein structure, and apatite crystal growth, we have measured supramolecular assembly dimensions in various vertebrates using atomic force microscopy, tested the effect of protein assemblies on crystal growth by electron microscopy, generated a transgenic mouse model to examine the effect of an abbreviated polyproline sequence on crystal growth, and determined the structure of polyproline repeat elements using 3D NMR. Our study shows that an increase in PXX/PXQ tandem repeat motif length results (i) in a compaction of protein matrix subunit dimensions, (ii) reduced conformational variability, (iii) an increase in polyproline II helices, and (iv) promotion of apatite crystal length. Together, these findings establish a direct relationship between polyproline tandem repeat fragment

  17. Elongated Polyproline Motifs Facilitate Enamel Evolution through Matrix Subunit Compaction

    PubMed Central

    Luan, Xianghong; Dangaria, Smit; Walker, Cameron; Allen, Michael; Kulkarni, Ashok; Gibson, Carolyn; Braatz, Richard; Liao, Xiubei; Diekwisch, Thomas G. H.

    2009-01-01

    Vertebrate body designs rely on hydroxyapatite as the principal mineral component of relatively light-weight, articulated endoskeletons and sophisticated tooth-bearing jaws, facilitating rapid movement and efficient predation. Biological mineralization and skeletal growth are frequently accomplished through proteins containing polyproline repeat elements. Through their well-defined yet mobile and flexible structure polyproline-rich proteins control mineral shape and contribute many other biological functions including Alzheimer's amyloid aggregation and prolamine plant storage. In the present study we have hypothesized that polyproline repeat proteins exert their control over biological events such as mineral growth, plaque aggregation, or viscous adhesion by altering the length of their central repeat domain, resulting in dramatic changes in supramolecular assembly dimensions. In order to test our hypothesis, we have used the vertebrate mineralization protein amelogenin as an exemplar and determined the biological effect of the four-fold increased polyproline tandem repeat length in the amphibian/mammalian transition. To study the effect of polyproline repeat length on matrix assembly, protein structure, and apatite crystal growth, we have measured supramolecular assembly dimensions in various vertebrates using atomic force microscopy, tested the effect of protein assemblies on crystal growth by electron microscopy, generated a transgenic mouse model to examine the effect of an abbreviated polyproline sequence on crystal growth, and determined the structure of polyproline repeat elements using 3D NMR. Our study shows that an increase in PXX/PXQ tandem repeat motif length results (i) in a compaction of protein matrix subunit dimensions, (ii) reduced conformational variability, (iii) an increase in polyproline II helices, and (iv) promotion of apatite crystal length. Together, these findings establish a direct relationship between polyproline tandem repeat fragment

  18. 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.

  19. Regularized Laplace-Fourier-Domain Full Waveform Inversion Using a Weighted l 2 Objective Function

    NASA Astrophysics Data System (ADS)

    Jun, Hyunggu; Kwon, Jungmin; Shin, Changsoo; Zhou, Hongbo; Cogan, Mike

    2017-03-01

    Full waveform inversion (FWI) can be applied to obtain an accurate velocity model that contains important geophysical and geological information. FWI suffers from the local minimum problem when the starting model is not sufficiently close to the true model. Therefore, an accurate macroscale velocity model is essential for successful FWI, and Laplace-Fourier-domain FWI is appropriate for obtaining such a velocity model. However, conventional Laplace-Fourier-domain FWI remains an ill-posed and ill-conditioned problem, meaning that small errors in the data can result in large differences in the inverted model. This approach also suffers from certain limitations related to the logarithmic objective function. To overcome the limitations of conventional Laplace-Fourier-domain FWI, we introduce a weighted l 2 objective function, instead of the logarithmic objective function, as the data-domain objective function, and we also introduce two different model-domain regularizations: first-order Tikhonov regularization and prior model regularization. The weighting matrix for the data-domain objective function is constructed to suitably enhance the far-offset information. Tikhonov regularization smoothes the gradient, and prior model regularization allows reliable prior information to be taken into account. Two hyperparameters are obtained through trial and error and used to control the trade-off and achieve an appropriate balance between the data-domain and model-domain gradients. The application of the proposed regularizations facilitates finding a unique solution via FWI, and the weighted l 2 objective function ensures a more reasonable residual, thereby improving the stability of the gradient calculation. Numerical tests performed using the Marmousi synthetic dataset show that the use of the weighted l 2 objective function and the model-domain regularizations significantly improves the Laplace-Fourier-domain FWI. Because the Laplace-Fourier-domain FWI is improved, the

  20. Regularized Laplace-Fourier-Domain Full Waveform Inversion Using a Weighted l 2 Objective Function

    NASA Astrophysics Data System (ADS)

    Jun, Hyunggu; Kwon, Jungmin; Shin, Changsoo; Zhou, Hongbo; Cogan, Mike

    2016-09-01

    Full waveform inversion (FWI) can be applied to obtain an accurate velocity model that contains important geophysical and geological information. FWI suffers from the local minimum problem when the starting model is not sufficiently close to the true model. Therefore, an accurate macroscale velocity model is essential for successful FWI, and Laplace-Fourier-domain FWI is appropriate for obtaining such a velocity model. However, conventional Laplace-Fourier-domain FWI remains an ill-posed and ill-conditioned problem, meaning that small errors in the data can result in large differences in the inverted model. This approach also suffers from certain limitations related to the logarithmic objective function. To overcome the limitations of conventional Laplace-Fourier-domain FWI, we introduce a weighted l 2 objective function, instead of the logarithmic objective function, as the data-domain objective function, and we also introduce two different model-domain regularizations: first-order Tikhonov regularization and prior model regularization. The weighting matrix for the data-domain objective function is constructed to suitably enhance the far-offset information. Tikhonov regularization smoothes the gradient, and prior model regularization allows reliable prior information to be taken into account. Two hyperparameters are obtained through trial and error and used to control the trade-off and achieve an appropriate balance between the data-domain and model-domain gradients. The application of the proposed regularizations facilitates finding a unique solution via FWI, and the weighted l 2 objective function ensures a more reasonable residual, thereby improving the stability of the gradient calculation. Numerical tests performed using the Marmousi synthetic dataset show that the use of the weighted l 2 objective function and the model-domain regularizations significantly improves the Laplace-Fourier-domain FWI. Because the Laplace-Fourier-domain FWI is improved, the

  1. 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.

  2. Motor imagery facilitates force field learning.

    PubMed

    Anwar, Muhammad Nabeel; Tomi, Naoki; Ito, Koji

    2011-06-13

    Humans have the ability to produce an internal reproduction of a specific motor action without any overt motor output. Recent findings show that the processes underlying motor imagery are similar to those active during motor execution and both share common neural substrates. This suggests that the imagery of motor movements might play an important role in acquiring new motor skills. In this study we used haptic robot in conjunction with motor imagery technique to improve learning in a robot-based adaptation task. Two groups of subjects performed reaching movements with or without motor imagery in a velocity-dependent and position-dependent mixed force field. The groups performed movements with motor imagery produced higher after effects and decreased muscle co-contraction with respect to no-motor imagery group. These results showed a positive influence of motor imagery on acquiring new motor skill and suggest that motor learning can be facilitated by mental practice and could be used to increase the rate of adaptation.

  3. Sleep facilitates long-term face adaptation.

    PubMed

    Ditye, Thomas; Javadi, Amir Homayoun; Carbon, Claus-Christian; Walsh, Vincent

    2013-10-22

    Adaptation is an automatic neural mechanism supporting the optimization of visual processing on the basis of previous experiences. While the short-term effects of adaptation on behaviour and physiology have been studied extensively, perceptual long-term changes associated with adaptation are still poorly understood. Here, we show that the integration of adaptation-dependent long-term shifts in neural function is facilitated by sleep. Perceptual shifts induced by adaptation to a distorted image of a famous person were larger in a group of participants who had slept (experiment 1) or merely napped for 90 min (experiment 2) during the interval between adaptation and test compared with controls who stayed awake. Participants' individual rapid eye movement sleep duration predicted the size of post-sleep behavioural adaptation effects. Our data suggest that sleep prevented decay of adaptation in a way that is qualitatively different from the effects of reduced visual interference known as 'storage'. In the light of the well-established link between sleep and memory consolidation, our findings link the perceptual mechanisms of sensory adaptation--which are usually not considered to play a relevant role in mnemonic processes--with learning and memory, and at the same time reveal a new function of sleep in cognition.

  4. An enhanced archive facilitating climate impacts analysis

    USGS Publications Warehouse

    Maurer, E.P.; Brekke, L.; Pruitt, T.; Thrasher, B.; Long, J.; Duffy, P.; Dettinger, M.; Cayan, D.; Arnold, J.

    2014-01-01

    We describe the expansion of a publicly available archive of downscaled climate and hydrology projections for the United States. Those studying or planning to adapt to future climate impacts demand downscaled climate model output for local or regional use. The archive we describe attempts to fulfill this need by providing data in several formats, selectable to meet user needs. Our archive has served as a resource for climate impacts modelers, water managers, educators, and others. Over 1,400 individuals have transferred more than 50 TB of data from the archive. In response to user demands, the archive has expanded from monthly downscaled data to include daily data to facilitate investigations of phenomena sensitive to daily to monthly temperature and precipitation, including extremes in these quantities. New developments include downscaled output from the new Coupled Model Intercomparison Project phase 5 (CMIP5) climate model simulations at both the monthly and daily time scales, as well as simulations of surface hydrologi- cal variables. The web interface allows the extraction of individual projections or ensemble statistics for user-defined regions, promoting the rapid assessment of model consensus and uncertainty for future projections of precipitation, temperature, and hydrology. The archive is accessible online (http://gdo-dcp.ucllnl.org/downscaled_ cmip_projections).

  5. Sleep facilitates long-term face adaptation

    PubMed Central

    Ditye, Thomas; Javadi, Amir Homayoun; Carbon, Claus-Christian; Walsh, Vincent

    2013-01-01

    Adaptation is an automatic neural mechanism supporting the optimization of visual processing on the basis of previous experiences. While the short-term effects of adaptation on behaviour and physiology have been studied extensively, perceptual long-term changes associated with adaptation are still poorly understood. Here, we show that the integration of adaptation-dependent long-term shifts in neural function is facilitated by sleep. Perceptual shifts induced by adaptation to a distorted image of a famous person were larger in a group of participants who had slept (experiment 1) or merely napped for 90 min (experiment 2) during the interval between adaptation and test compared with controls who stayed awake. Participants' individual rapid eye movement sleep duration predicted the size of post-sleep behavioural adaptation effects. Our data suggest that sleep prevented decay of adaptation in a way that is qualitatively different from the effects of reduced visual interference known as ‘storage’. In the light of the well-established link between sleep and memory consolidation, our findings link the perceptual mechanisms of sensory adaptation—which are usually not considered to play a relevant role in mnemonic processes—with learning and memory, and at the same time reveal a new function of sleep in cognition. PMID:23986109

  6. Facilitated auditory detection for speech sounds.

    PubMed

    Signoret, Carine; Gaudrain, Etienne; Tillmann, Barbara; Grimault, Nicolas; Perrin, Fabien

    2011-01-01

    If it is well known that knowledge facilitates higher cognitive functions, such as visual and auditory word recognition, little is known about the influence of knowledge on detection, particularly in the auditory modality. Our study tested the influence of phonological and lexical knowledge on auditory detection. Words, pseudo-words, and complex non-phonological sounds, energetically matched as closely as possible, were presented at a range of presentation levels from sub-threshold to clearly audible. The participants performed a detection task (Experiments 1 and 2) that was followed by a two alternative forced-choice recognition task in Experiment 2. The results of this second task in Experiment 2 suggest a correct recognition of words in the absence of detection with a subjective threshold approach. In the detection task of both experiments, phonological stimuli (words and pseudo-words) were better detected than non-phonological stimuli (complex sounds), presented close to the auditory threshold. This finding suggests an advantage of speech for signal detection. An additional advantage of words over pseudo-words was observed in Experiment 2, suggesting that lexical knowledge could also improve auditory detection when listeners had to recognize the stimulus in a subsequent task. Two simulations of detection performance performed on the sound signals confirmed that the advantage of speech over non-speech processing could not be attributed to energetic differences in the stimuli.

  7. The epidemiology of drug facilitated sexual assault.

    PubMed

    Hurley, Michael; Parker, Helen; Wells, David L

    2006-05-01

    The files of the Victorian Institute of Forensic Medicine were reviewed for all cases of alleged drug facilitated sexual assault for the 12 month period concluding in April 2003. Seventy-six cases were identified from a total of 434 (17.5%) cases of adult sexual assault. The median delay from alleged incident to time of examination was 20 h. Alcohol consumption in the hours prior to the assault was reported by 77%. Alcohol was still present in 37% when subsequently examined, with an average blood alcohol concentration of 0.11% at the time of examination. Forty-nine percent reported using prescription medications and 26% reported the use of recreational drugs. Drugs not reportedly consumed by the subject were detected in 15 cases (20%) of the study group or 3% of all adult sexual assault cases. The drugs detected included cannabis (four cases), antidepressants (4), amphetamines (3), benzodiazepines (4) and opiates (3). The study indicates that covert administration of drugs in the setting of adult sexual assault appears uncommon. The true incidence however may be higher (due to non or delayed reporting) or lower (due to inaccurate self reporting of drug consumption) however the frequent findings of high concentrations of alcohol has implications for the health and safety of these individuals.

  8. Challenges of Drug-Facilitated Sexual Assault.

    PubMed

    LeBeau, M A; Montgomery, M A

    2010-01-01

    This article provides the reader with an understanding of the numerous challenges of drug-facilitated sexual assaults (DFSA). The challenges are categorized as follows: the drugs, reporting the crime, evidence collection, and laboratory analysis of specimens. The challenges associated with the drugs used to commit DFSA emphasizes the pharmacological effects of strong central nervous system depressants and how the pharmacokinetics and pharmacodynamics of these drugs create difficulties in an investigation. For example, while sexual assaults are generally considered to be a significantly underreported crime, the drug effects further complicate victims' reporting to law enforcement. Any delay in reporting decreases the ability of a laboratory to detect the presence of drugs or metabolites in useful evidentiary specimens such as blood and urine. Finally, differences in instrumentation and mission from one laboratory to the next will impact the ability to provide consistent identification of DFSA drugs or metabolites in these cases. Although the true prevalence of DFSAs will never be fully known, acknowledgment of the many challenges that come with these cases provides insight as to how to improve chances of successfully investigating DFSA allegations.

  9. Protected areas facilitate species’ range expansions

    PubMed Central

    Thomas, Chris D.; Gillingham, Phillipa K.; Bradbury, Richard B.; Roy, David B.; Anderson, Barbara J.; Baxter, John M.; Bourn, Nigel A. D.; Crick, Humphrey Q. P.; Findon, Richard A.; Fox, Richard; Hodgson, Jenny A.; Holt, Alison R.; Morecroft, Mike D.; O’Hanlon, Nina J.; Oliver, Tom H.; Pearce-Higgins, James W.; Procter, Deborah A.; Thomas, Jeremy A.; Walker, Kevin J.; Walmsley, Clive A.; Wilson, Robert J.; Hill, Jane K.

    2012-01-01

    The benefits of protected areas (PAs) for biodiversity have been questioned in the context of climate change because PAs are static, whereas the distributions of species are dynamic. Current PAs may, however, continue to be important if they provide suitable locations for species to colonize at their leading-edge range boundaries, thereby enabling spread into new regions. Here, we present an empirical assessment of the role of PAs as targets for colonization during recent range expansions. Records from intensive surveys revealed that seven bird and butterfly species have colonized PAs 4.2 (median) times more frequently than expected from the availability of PAs in the landscapes colonized. Records of an additional 256 invertebrate species with less-intensive surveys supported these findings and showed that 98% of species are disproportionately associated with PAs in newly colonized parts of their ranges. Although colonizing species favor PAs in general, species vary greatly in their reliance on PAs, reflecting differences in the dependence of individual species on particular habitats and other conditions that are available only in PAs. These findings highlight the importance of current PAs for facilitating range expansions and show that a small subset of the landscape receives a high proportion of colonizations by range-expanding species. PMID:22893689

  10. Free radical facilitated damage of ungual keratin.

    PubMed

    Khengar, Rajeshree H; Brown, Marc B; Turner, Rob B; Traynor, Matthew J; Holt, Katherine B; Jones, Stuart A

    2010-09-01

    Thioglycolic acid (TA) and urea hydrogen peroxide (urea H(2)O(2)) are thought to disrupt alpha-keratin disulfide links in the nail. However, optimal clinical use of these agents to improve the treatment of nail disorders is currently hindered by a lack of fundamental data to support their mechanism of action. The aim of this study was to investigate how the redox environment of ungual keratin, when manipulated by TA and urea H(2)O(2), influenced the properties of the nail barrier. Potentiometric and voltammetric measurements demonstrated that urea H(2)O(2) obeyed the Nernst equation for a proton coupled one-electron transfer redox process while TA underwent a series of redox reactions that was complicated by electrode adsorption and dimer formation. The functional studies demonstrated that nail permeability, measured through TBF penetration (38.51+/-10.94 microg/cm(2)/h) and nail swelling (244.10+/-14.99% weight increase), was greatest when relatively low concentrations of the thiolate ion were present in the applied solution. Limiting the thiolate ion to low levels in the solution retards thiolate dimerisation and generates thiyl free radicals. It appeared that this free radical generation was fundamental in facilitating the redox-mediated keratin disruption of the ungual membrane.

  11. Contrast, induction, facilitation, suppression, and conservation1

    PubMed Central

    Allison, James

    1976-01-01

    Ten rats received all of their water in daily 1-hr sessions. Following a baseline phase in which lever and water spout were freely available throughout each session, subjects were trained to press the lever for water on mixed schedules composed of two alternating components. Each component gave access to water for a fixed cumulation of drinking time every time the rat cumulated a fixed amount of lever-pressing time. Changes in one component produced contrast and induction effects, both positive and negative, with respect to both lever pressing and drinking in the unchanged component. All schedules facilitated lever pressing relative to baseline. All schedules suppressed drinking relative to baseline, even though contingency sessions allowed ample time to perform the baseline amount of drinking. The entire pattern of results was predicted in quantitative detail by assuming that the total amount of a dimension apportioned to lever pressing and drinking is conserved between baseline and contingency sessions. Conservation theory was shown to predict several effects produced by simple fixed-ratio schedules, and was compared favorably with probability-differential (Premack, 1971) and response-deprivation (Timberlake and Allison, 1974) theory. PMID:16811902

  12. Interspecific competition/facilitation among insect parasitoids.

    PubMed

    Cusumano, Antonino; Peri, Ezio; Colazza, Stefano

    2016-04-01

    Competition for limited resources is a widespread ecological interaction in animals. In the case of insect parasitoids, species can compete for host resources both at the adult stage as well as at the larval stage. Interspecific competition can play a role in sizing and shaping community structures. In addition of being relevant for basic ecological studies, understanding how interspecific competition between parasitoids affects pest suppression is important for biological control. In this opinion paper we review recent advances in the field of interspecific competition among parasitoids in a biological control perspective. We first discuss adult competition, highlighting which factors are likely to play a role in the outcome of competition when adults interact either directly or indirectly. Then we focus on the interactions occurring between competing larvae that develop within the same host taking also into account the fitness consequences of competition for the larva surviving interspecific competition. We also explore the possibility of interspecific facilitation among parasitoids in those situations in which a given species may benefit from interspecific competition.

  13. Anthocyanins facilitate tungsten accumulation in Brassica

    SciTech Connect

    Hale, K.L.

    2002-11-01

    Accumulation of molybdenum in Brassica was recently found to be correlated with anthocyanin content, involving the formation of a blue complex. Here the role of anthocyanins in tungsten sequestration was investigated using three species of Brassica: B. rapa (cv. Fast plants), B. juncea (Indian mustard) and B. oleracea (red cabbage). Seedlings of B. rapa and B. juncea turned blue when supplied with colourless tungstate. The blue compound co-localized with anthocyanins in the peripheral cell layers, and the degree of blueness was correlated with anthocyanin content. The direct involvement of anthocyanins in the blue coloration was evident when purified anthocyanins showed a colour change from pink to blue in vitro upon addition of tungstate, over a wide pH range. Anthocyanin production was upregulated 3-fold by W in B. juncea, possibly reflecting a function for anthocyanins in W tolerance or sequestration. The presence of anthocyanins facilitated W accumulation in B. rapa: anthocyanin-containing seedlings accumulated 3-fold more W than an anthocyaninless mutant. There was no correlation between anthocyanin content and W tolerance under these conditions. The nature of the interaction between anthocyanins and tungstate was investigated. X-ray absorption spectroscopy showed no change in the local chemical environment of Wupon uptake of tungstate by the plant; HPLC analysis of purified anthocyanin with or without tungstate showed no peak shift after metal treatment.

  14. Spatiotopic updating facilitates perception immediately after saccades

    PubMed Central

    Fabius, Jasper H.; Fracasso, Alessio; Van der Stigchel, Stefan

    2016-01-01

    As the neural representation of visual information is initially coded in retinotopic coordinates, eye movements (saccades) pose a major problem for visual stability. If no visual information were maintained across saccades, retinotopic representations would have to be rebuilt after each saccade. It is currently strongly debated what kind of information (if any at all) is accumulated across saccades, and when this information becomes available after a saccade. Here, we use a motion illusion to examine the accumulation of visual information across saccades. In this illusion, an annulus with a random texture slowly rotates, and is then replaced with a second texture (motion transient). With increasing rotation durations, observers consistently perceive the transient as large rotational jumps in the direction opposite to rotation direction (backward jumps). We first show that accumulated motion information is updated spatiotopically across saccades. Then, we show that this accumulated information is readily available after a saccade, immediately biasing postsaccadic perception. The current findings suggest that presaccadic information is used to facilitate postsaccadic perception and are in support of a forward model of transsaccadic perception, aiming at anticipating the consequences of eye movements and operating within the narrow perisaccadic time window. PMID:27686998

  15. Open rhinoplasty concepts in facilitating tip reconstruction.

    PubMed

    Carminati, Marcello; Robotti, Enrico

    2014-06-01

    The nose is a frequent site for skin cancer, accounting for approximately 26% of basal cell carcinomas and approximately 13% of spinal cell carcinomas of the facial district. Also melanomas, mostly as lentigo maligna melanomas, are frequently located at the nasal pyramid. Although defects can be of varying size and depth, some even involving the whole trilaminar structure of the nose, most remain superficial and seldom reach and infiltrate the underlying framework. In contrast, they can be wide, thus requesting large flaps to resurface the defect. Although a technically well-planned and well-performed surgery can lead to excellent aesthetic results, scars from both donor and recipient sites can be noticeable. Since skin cancers generally affect older people, we often deal with aged noses. Such noses typically present some common features such as plunging tip, increased length, and a prominent hump due to several reasons, already well described in the literature. In this scenario, by reducing and addressing the framework, we can obtain a variable quota of downsizing of the original defect, thus requiring less skin for coverage, and thus reducing the size of needed flaps and consequent scars. This is greatly facilitated by the open rhinoplasty approach. Most of the maneuvers aimed at reducing the framework are indeed the same.

  16. Oxytocin: the Great Facilitator of Life

    PubMed Central

    Lee, Heon-Jin; Macbeth, Abbe H.; Pagani, Jerome; Young, W. Scott

    2009-01-01

    Oxytocin (Oxt) is a nonapeptide hormone best known for its role in lactation and parturition. Since 1906 when its uterine-contracting properties were described until 50 years later when its sequence was elucidated, research focused on its peripheral roles in reproduction. Only over the past several decades have researchers focused on what functions Oxt might have in the brain, the subject of this review. Immunohistochemical studies revealed that magnocellular neurons of the hypothalamic paraventricular and supraoptic nuclei are the neurons of origin for the Oxt released from the posterior pituitary. Smaller cells in various parts of the brain, as well as release from magnocellular dendrites, provide the Oxt responsible for modulating various behaviors at its only identified receptor. Although Oxt is implicated in a variety of “non-social” behaviors, such as learning, anxiety, feeding and pain perception, it is Oxt’s roles in various social behaviors that have come to the fore recently. Oxt is important for social memory and attachment, sexual and maternal behavior, and aggression. Recent work implicates Oxt in human bonding and trust as well. Human disorders characterized by aberrant social interactions, such as autism and schizophrenia, may also involve Oxt expression. Many, if not most, of Oxt’s functions, from social interactions (affiliation, aggression) and sexual behavior to eventual parturition, lactation and maternal behavior, may be viewed as specifically facilitating PMID:19482229

  17. Transducer model produces facilitation from opposite-sign flanks

    NASA Technical Reports Server (NTRS)

    Solomon, J. A.; Watson, A. B.; Morgan, M. J.

    1999-01-01

    Small spots, lines and Gabor patterns can be easier to detect when they are superimposed upon similar spots, lines and Gabor patterns. Traditionally, such facilitation has been understood to be a consequence of nonlinear contrast transduction. Facilitation has also been reported to arise from non-overlapping patterns with opposite sign. We point out that this result does not preclude the traditional explanation for superimposed targets. Moreover, we find that facilitation from opposite-sign flanks is weaker than facilitation from same-sign flanks. Simulations with a transducer model produce opposite-sign facilitation.

  18. Anomalous excitation facilitation in inhomogeneously broadened Rydberg gases

    NASA Astrophysics Data System (ADS)

    Letscher, F.; Thomas, O.; Niederprüm, T.; Ott, H.; Fleischhauer, M.

    2017-02-01

    When atomic gases are laser driven to Rydberg states in an off-resonant way, a single Rydberg atom may enhance the excitation rate of surrounding atoms. This leads to a facilitated excitation referred to as Rydberg antiblockade. In the usual facilitation scenario, the detuning of the laser from resonance compensates the interaction shift. Here, we discuss a different excitation mechanism, which we call anomalous facilitation. This occurs on the "wrong side" of the resonance and originates from inhomogeneous broadening. The anomalous facilitation may be seen in experiments of attractively interacting atoms on the blue detuned side, where facilitation is not expected to appear.

  19. Human HLTF mediates postreplication repair by its HIRAN domain-dependent replication fork remodelling

    PubMed Central

    Achar, Yathish Jagadheesh; Balogh, David; Neculai, Dante; Juhasz, Szilvia; Morocz, Monika; Gali, Himabindu; Dhe-Paganon, Sirano; Venclovas, Česlovas; Haracska, Lajos

    2015-01-01

    Defects in the ability to respond properly to an unrepaired DNA lesion blocking replication promote genomic instability and cancer. Human HLTF, implicated in error-free replication of damaged DNA and tumour suppression, exhibits a HIRAN domain, a RING domain, and a SWI/SNF domain facilitating DNA-binding, PCNA-polyubiquitin-ligase, and dsDNA-translocase activities, respectively. Here, we investigate the mechanism of HLTF action with emphasis on its HIRAN domain. We found that in cells HLTF promotes the filling-in of gaps left opposite damaged DNA during replication, and this postreplication repair function depends on its HIRAN domain. Our biochemical assays show that HIRAN domain mutant HLTF proteins retain their ubiquitin ligase, ATPase and dsDNA translocase activities but are impaired in binding to a model replication fork. These data and our structural study indicate that the HIRAN domain recruits HLTF to a stalled replication fork, and it also provides the direction for the movement of the dsDNA translocase motor domain for fork reversal. In more general terms, we suggest functional similarities between the HIRAN, the OB, the HARP2, and other domains found in certain motor proteins, which may explain why only a subset of DNA translocases can carry out fork reversal. PMID:26350214

  20. Human HLTF mediates postreplication repair by its HIRAN domain-dependent replication fork remodelling

    DOE PAGES

    Achar, Yathish Jagadheesh; Balogh, David; Neculai, Dante; ...

    2015-09-08

    Defects in the ability to respond properly to an unrepaired DNA lesion blocking replication promote genomic instability and cancer. Human HLTF, implicated in error-free replication of damaged DNA and tumour suppression, exhibits a HIRAN domain, a RING domain, and a SWI/SNF domain facilitating DNA-binding, PCNA-polyubiquitin-ligase, and dsDNA-translocase activities, respectively. Here, we investigate the mechanism of HLTF action with emphasis on its HIRAN domain. We found that in cells HLTF promotes the filling-in of gaps left opposite damaged DNA during replication, and this postreplication repair function depends on its HIRAN domain. Our biochemical assays show that HIRAN domain mutant HLTF proteinsmore » retain their ubiquitin ligase, ATPase and dsDNA translocase activities but are impaired in binding to a model replication fork. These data and our structural study indicate that the HIRAN domain recruits HLTF to a stalled replication fork, and it also provides the direction for the movement of the dsDNA translocase motor domain for fork reversal. We suggest functional similarities between the HIRAN, the OB, the HARP2, and other domains found in certain motor proteins, which may explain why only a subset of DNA translocases can carry out fork reversal.« less

  1. Human HLTF mediates postreplication repair by its HIRAN domain-dependent replication fork remodelling

    SciTech Connect

    Achar, Yathish Jagadheesh; Balogh, David; Neculai, Dante; Juhasz, Szilvia; Morocz, Monika; Gali, Himabindu; Dhe-Paganon, Sirano; Venclovas, Česlovas; Haracska, Lajos

    2015-09-08

    Defects in the ability to respond properly to an unrepaired DNA lesion blocking replication promote genomic instability and cancer. Human HLTF, implicated in error-free replication of damaged DNA and tumour suppression, exhibits a HIRAN domain, a RING domain, and a SWI/SNF domain facilitating DNA-binding, PCNA-polyubiquitin-ligase, and dsDNA-translocase activities, respectively. Here, we investigate the mechanism of HLTF action with emphasis on its HIRAN domain. We found that in cells HLTF promotes the filling-in of gaps left opposite damaged DNA during replication, and this postreplication repair function depends on its HIRAN domain. Our biochemical assays show that HIRAN domain mutant HLTF proteins retain their ubiquitin ligase, ATPase and dsDNA translocase activities but are impaired in binding to a model replication fork. These data and our structural study indicate that the HIRAN domain recruits HLTF to a stalled replication fork, and it also provides the direction for the movement of the dsDNA translocase motor domain for fork reversal. We suggest functional similarities between the HIRAN, the OB, the HARP2, and other domains found in certain motor proteins, which may explain why only a subset of DNA translocases can carry out fork reversal.

  2. C-type lectins facilitate tumor metastasis

    PubMed Central

    Ding, Dongbing; Yao, Yao; Zhang, Songbai; Su, Chunjie; Zhang, Yonglian

    2017-01-01

    Metastasis, a life-threatening complication of cancer, leads to the majority of cases of cancer-associated mortality. Unfortunately, the underlying molecular and cellular mechanisms of cancer metastasis remain to be fully elucidated. C-type lectins are a large group of proteins, which share structurally homologous carbohydrate-recognition domains (CRDs) and possess diverse physiological functions, including inflammation and antimicrobial immunity. Accumulating evidence has demonstrated the contribution of C-type lectins in different steps of the metastatic spread of cancer. Notably, a substantial proportion of C-type lectins, including selectins, mannose receptor (MR) and liver and lymph node sinusoidal endothelial cell C-type lectin, are important molecular targets for the formation of metastases in vitro and in vivo. The present review summarizes what has been found regarding C-type lectins in the lymphatic and hematogenous metastasis of cancer. An improved understanding the role of C-type lectins in cancer metastasis provides a comprehensive perspective for further clarifying the molecular mechanisms of cancer metastasis and supports the development of novel C-type lectins-based therapies the for prevention of metastasis in certain types of cancer. PMID:28123516

  3. C-type lectins facilitate tumor metastasis.

    PubMed

    Ding, Dongbing; Yao, Yao; Zhang, Songbai; Su, Chunjie; Zhang, Yonglian

    2017-01-01

    Metastasis, a life-threatening complication of cancer, leads to the majority of cases of cancer-associated mortality. Unfortunately, the underlying molecular and cellular mechanisms of cancer metastasis remain to be fully elucidated. C-type lectins are a large group of proteins, which share structurally homologous carbohydrate-recognition domains (CRDs) and possess diverse physiological functions, including inflammation and antimicrobial immunity. Accumulating evidence has demonstrated the contribution of C-type lectins in different steps of the metastatic spread of cancer. Notably, a substantial proportion of C-type lectins, including selectins, mannose receptor (MR) and liver and lymph node sinusoidal endothelial cell C-type lectin, are important molecular targets for the formation of metastases in vitro and in vivo. The present review summarizes what has been found regarding C-type lectins in the lymphatic and hematogenous metastasis of cancer. An improved understanding the role of C-type lectins in cancer metastasis provides a comprehensive perspective for further clarifying the molecular mechanisms of cancer metastasis and supports the development of novel C-type lectins-based therapies the for prevention of metastasis in certain types of cancer.

  4. Facilitating Collaboration Through Linked Open Data

    NASA Astrophysics Data System (ADS)

    Narock, T. W.; Rozell, E. A.; Robinson, E. M.

    2012-12-01

    The increasing volumes, complexity, and heterogeneity of scientific data are requiring members of formally disparate disciplines to come together to address today's scientific challenges. Data science is formed at the intersection of domain scientists, information specialists, librarians, computer scientists and data managers. With such a distributed and diverse community, it can be difficult to identify collaborators, keep track of current research, and assess the underlying social network. We introduce the notion of data science within the Earth and space sciences and present a novel tool for understanding the evolving research network. Linked Data, a modern paradigm for data publishing, leverages the inherent linking capabilities of the Web. Additionally, Linked Data is a machine understandable data format that enables computational reasoning and inferencing. Using this concept, we have linked data from a number of disparate sources such as, hundreds of thousands of AGU abstracts, National Science Foundation project information, people, and organizations. We highlight new collaborations and insights enabled by visualizing the relationships between publications, science data, people, organizations, and events and discuss how such an approach can benefit with extensions from the community at large.

  5. Natural frequencies facilitate diagnostic inferences of managers

    PubMed Central

    Hoffrage, Ulrich; Hafenbrädl, Sebastian; Bouquet, Cyril

    2015-01-01

    In Bayesian inference tasks, information about base rates as well as hit rate and false-alarm rate needs to be integrated according to Bayes’ rule after the result of a diagnostic test became known. Numerous studies have found that presenting information in a Bayesian inference task in terms of natural frequencies leads to better performance compared to variants with information presented in terms of probabilities or percentages. Natural frequencies are the tallies in a natural sample in which hit rate and false-alarm rate are not normalized with respect to base rates. The present research replicates the beneficial effect of natural frequencies with four tasks from the domain of management, and with management students as well as experienced executives as participants. The percentage of Bayesian responses was almost twice as high when information was presented in natural frequencies compared to a presentation in terms of percentages. In contrast to most tasks previously studied, the majority of numerical responses were lower than the Bayesian solutions. Having heard of Bayes’ rule prior to the study did not affect Bayesian performance. An implication of our work is that textbooks explaining Bayes’ rule should teach how to represent information in terms of natural frequencies instead of how to plug probabilities or percentages into a formula. PMID:26157397

  6. Functional domain walls in multiferroics.

    PubMed

    Meier, Dennis

    2015-11-25

    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. Sustained Hypoxia Elicits Competing Spinal Mechanisms of Phrenic Motor Facilitation

    PubMed Central

    Devinney, Michael J.; Nichols, Nicole L.

    2016-01-01

    Acute intermittent hypoxia (AIH) induces phrenic long-term facilitation (pLTF), a form of spinal motor plasticity. Competing mechanisms give rise to phrenic motor facilitation (pMF; a general term including pLTF) depending on the severity of hypoxia within episodes. In contrast, moderate acute sustained hypoxia (mASH) does not elicit pMF. By varying the severity of ASH and targeting competing mechanisms of pMF, we sought to illustrate why moderate AIH (mAIH) elicits pMF but mASH does not. Although mAIH elicits serotonin-dependent pLTF, mASH does not; thus, mAIH-induced pLTF is pattern sensitive. In contrast, severe AIH (sAIH) elicits pLTF through adenosine-dependent mechanisms, likely from greater extracellular adenosine accumulation. Because serotonin- and adenosine-dependent pMF interact via cross talk inhibition, we hypothesized that pMF is obscured because the competing mechanisms of pMF are balanced and offsetting during mASH. Here, we demonstrate the following: (1) blocking spinal A2A receptors with MSX-3 reveals mASH-induced pMF; and (2) sASH elicits A2A-dependent pMF. In anesthetized rats pretreated with intrathecal A2A receptor antagonist injections before mASH (PaO2 = 40–54 mmHg) or sASH (PaO2 = 25–36 mmHg), (1) mASH induced a serotonin-dependent pMF and (2) sASH induced an adenosine-dependent pMF, which was enhanced by spinal serotonin receptor inhibition. Thus, competing adenosine- and serotonin-dependent mechanisms contribute differentially to pMF depending on the pattern/severity of hypoxia. Understanding interactions between these mechanisms has clinical relevance as we develop therapies to treat severe neuromuscular disorders that compromise somatic motor behaviors, including breathing. Moreover, these results demonstrate how competing mechanisms of plasticity can give rise to pattern sensitivity in pLTF. SIGNIFICANCE STATEMENT Intermittent hypoxia elicits pattern-sensitive spinal plasticity and improves motor function after spinal injury or

  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. Metadherin facilitates podocyte apoptosis in diabetic nephropathy

    PubMed Central

    Liu, Wen-Ting; Peng, Fen-Fen; Li, Hong-Yu; Chen, Xiao-Wen; Gong, Wang-Qiu; Chen, Wen-Jing; Chen, Yi-Hua; Li, Pei-Lin; Li, Shu-Ting; Xu, Zhao-Zhong; Long, Hai-Bo

    2016-01-01

    Apoptosis, one of the major causes of podocyte loss, has been reported to have a vital role in diabetic nephropathy (DN) pathogenesis, and understanding the mechanisms underlying the regulation of podocyte apoptosis is crucial. Metadherin (MTDH) is an important oncogene, which is overexpressed in most cancers and responsible for apoptosis, metastasis, and poor patient survival. Here we show that the expression levels of Mtdh and phosphorylated p38 mitogen-activated protein kinase (MAPK) are significantly increased, whereas those of the microRNA-30 family members (miR-30s) are considerably reduced in the glomeruli of DN rat model and in high glucose (HG)-induced conditionally immortalized mouse podocytes (MPC5). These levels are positively correlated with podocyte apoptosis rate. The inhibition of Mtdh expression, using small interfering RNA, but not Mtdh overexpression, was shown to inhibit HG-induced MPC5 apoptosis and p38 MAPK pathway, and Bax and cleaved caspase 3 expression. This was shown to be similar to the effects of p38 MAPK inhibitor (SB203580). Furthermore, luciferase assay results demonstrated that Mtdh represents the target of miR-30s. Transient transfection experiments, using miR-30 microRNA (miRNA) inhibitors, led to the increase in Mtdh expression and induced the apoptosis of MPC5, whereas the treatment with miR-30 miRNA mimics led to the reduction in Mtdh expression and apoptosis of HG-induced MPC5 cells in comparison with their respective controls. Our results demonstrate that Mtdh is a potent modulator of podocyte apoptosis, and that it represents the target of miR-30 miRNAs, facilitating podocyte apoptosis through the activation of HG-induced p38 MAPK-dependent pathway. PMID:27882943

  10. Sleep facilitates learning a new linguistic rule

    PubMed Central

    Batterink, Laura J.; Oudiette, Delphine; Reber, Paul J.; Paller, Ken A.

    2014-01-01

    Natural languages contain countless regularities. Extraction of these patterns is an essential component of language acquisition. Here we examined the hypothesis that memory processing during sleep contributes to this learning. We exposed participants to a hidden linguistic rule by presenting a large number of two-word phrases, each including a noun preceded by one of four novel words that functioned as an article (e.g., gi rhino). These novel words (ul, gi, ro and ne) were presented as obeying an explicit rule: two words signified that the noun referent was relatively near, and two that it was relatively far. Undisclosed to participants was the fact that the novel articles also predicted noun animacy, with two of the articles preceding animate referents and the other two preceding inanimate referents. Rule acquisition was tested implicitly using a task in which participants responded to each phrase according to whether the noun was animate or inanimate. Learning of the hidden rule was evident in slower responses to phrases that violated the rule. Responses were delayed regardless of whether rule-knowledge was consciously accessible. Brain potentials provided additional confirmation of implicit and explicit rule-knowledge. An afternoon nap was interposed between two 20-min learning sessions. Participants who obtained greater amounts of both slow-wave and rapid-eye-movement sleep showed increased sensitivity to the hidden linguistic rule in the second session. We conclude that during sleep, reactivation of linguistic information linked with the rule was instrumental for stabilizing learning. The combination of slow-wave and rapid-eye-movement sleep may synergistically facilitate the abstraction of complex patterns in linguistic input. PMID:25447376

  11. Facilitating Analysis of Multiple Partial Data Streams

    NASA Technical Reports Server (NTRS)

    Maimone, Mark W.; Liebersbach, Robert R.

    2008-01-01

    Robotic Operations Automation: Mechanisms, Imaging, Navigation report Generation (ROAMING) is a set of computer programs that facilitates and accelerates both tactical and strategic analysis of time-sampled data especially the disparate and often incomplete streams of Mars Explorer Rover (MER) telemetry data described in the immediately preceding article. As used here, tactical refers to the activities over a relatively short time (one Martian day in the original MER application) and strategic refers to a longer time (the entire multi-year MER missions in the original application). Prior to installation, ROAMING must be configured with the types of data of interest, and parsers must be modified to understand the format of the input data (many example parsers are provided, including for general CSV files). Thereafter, new data from multiple disparate sources are automatically resampled into a single common annotated spreadsheet stored in a readable space-separated format, and these data can be processed or plotted at any time scale. Such processing or plotting makes it possible to study not only the details of a particular activity spanning only a few seconds, but also longer-term trends. ROAMING makes it possible to generate mission-wide plots of multiple engineering quantities [e.g., vehicle tilt as in Figure 1(a), motor current, numbers of images] that, heretofore could be found only in thousands of separate files. ROAMING also supports automatic annotation of both images and graphs. In the MER application, labels given to terrain features by rover scientists and engineers are automatically plotted in all received images based on their associated camera models (see Figure 2), times measured in seconds are mapped to Mars local time, and command names or arbitrary time-labeled events can be used to label engineering plots, as in Figure 1(b).

  12. Does polyploidy facilitate long-distance dispersal?

    PubMed Central

    Linder, H. Peter; Barker, Nigel P.

    2014-01-01

    Background and Aims The ability of plant lineages to reach all continents contributes substantially to their evolutionary success. This is exemplified by the Poaceae, one of the most successful angiosperm families, in which most higher taxa (tribes, subfamilies) have global distributions. Due to the old age of the ocean basins relative to the major angiosperm radiations, this is only possible by means of long-distance dispersal (LDD), yet the attributes of lineages with successful LDD remain obscure. Polyploid species are over-represented in invasive floras and in the previously glaciated Arctic regions, and often have wider ecological tolerances than diploids; thus polyploidy is a candidate attribute of successful LDD. Methods The link between polyploidy and LDD was explored in the globally distributed grass subfamily Danthonioideae. An almost completely sampled and well-resolved species-level phylogeny of the danthonioids was used, and the available cytological information was assembled. The cytological evolution in the clade was inferred using maximum likelihood (ML) as implemented in ChromEvol. The biogeographical evolution in the clade was reconstructed using ML and Bayesian approaches. Key Results Numerous increases in ploidy level are demonstrated. A Late Miocene–Pliocene cycle of polyploidy is associated with LDD, and in two cases (the Australian Rytidosperma and the American Danthonia) led to secondary polyploidy. While it is demonstrated that successful LDD is more likely in polyploid than in diploid lineages, a link between polyploidization events and LDD is not demonstrated. Conclusions The results suggest that polyploids are more successful at LDD than diploids, and that the frequent polyploidy in the grasses might have facilitated the extensive dispersal among continents in the family, thus contributing to their evolutionary success. PMID:24694830

  13. Sleep facilitates learning a new linguistic rule.

    PubMed

    Batterink, Laura J; Oudiette, Delphine; Reber, Paul J; Paller, Ken A

    2014-12-01

    Natural languages contain countless regularities. Extraction of these patterns is an essential component of language acquisition. Here we examined the hypothesis that memory processing during sleep contributes to this learning. We exposed participants to a hidden linguistic rule by presenting a large number of two-word phrases, each including a noun preceded by one of four novel words that functioned as an article (e.g., gi rhino). These novel words (ul, gi, ro and ne) were presented as obeying an explicit rule: two words signified that the noun referent was relatively near, and two that it was relatively far. Undisclosed to participants was the fact that the novel articles also predicted noun animacy, with two of the articles preceding animate referents and the other two preceding inanimate referents. Rule acquisition was tested implicitly using a task in which participants responded to each phrase according to whether the noun was animate or inanimate. Learning of the hidden rule was evident in slower responses to phrases that violated the rule. Responses were delayed regardless of whether rule-knowledge was consciously accessible. Brain potentials provided additional confirmation of implicit and explicit rule-knowledge. An afternoon nap was interposed between two 20-min learning sessions. Participants who obtained greater amounts of both slow-wave and rapid-eye-movement sleep showed increased sensitivity to the hidden linguistic rule in the second session. We conclude that during sleep, reactivation of linguistic information linked with the rule was instrumental for stabilizing learning. The combination of slow-wave and rapid-eye-movement sleep may synergistically facilitate the abstraction of complex patterns in linguistic input.

  14. Sinh-domain complex integrators

    NASA Astrophysics Data System (ADS)

    Skotis, George-Drosos; Khanday, Farooq A.; Psychalinos, Costas

    2015-07-01

    The basic building blocks for performing complex signal processing in the Sinh-domain are introduced in this article. Attractive offered benefits are the capabilities for achieving resistorless realisations with electronic adjustment of their frequency characteristics, independent tuning of centre frequency and bandwidth and operating in a low-voltage environment. In addition, the inherent class-AB operation of Sinh-domain filters allows the handling of signals greater than the bias current, leading to a power saving. The aforementioned benefits have been evaluated through simulation results, using the Analog Design Environment of the Cadence software.

  15. Neighborhood functions alter unbalanced facilitation on a stress gradient.

    PubMed

    Malanson, George P; Resler, Lynn M

    2015-01-21

    The stress-gradient hypothesis states that individual and species competitive and facilitative effects change in relative importance or intensity along environmental gradients of stress. The importance of the number of facilitators in the neighborhood of a potential beneficiary has not been explored. Evenly distributed and stress-correlated facilitation and the increase in the intensity of facilitation with neighbors as linear, logarithmic, and unimodal functions is simulated for two hypothetical species, both of which improve the local environment. The mutualism is unbalanced in that the establishment of one species is enhanced by neighbors more than the other. Compared to no facilitation or evenly distributed facilitation, the stress gradient produces more edges in the spatially advancing population, more overall intensity of facilitation, and more individuals further advanced into the area of higher stress; the more enhanced species has increased population relative to the other - to the point where they are equal. Among three neighborhood functions, little difference exists in outcomes between the linear and logarithmic functions, but the unimodal function, which shifts peak facilitation intensity to fewer neighbors, increases the above state variables more than the differences between the even and stress gradient facilitation scenarios; the population of the beneficiary species exceeds that of the other. Different neighborhood functions change the effects of spatial pattern on the biological outcome. The unbalanced mutualism may be important where additional species alter the basic interaction in the high stress area of the environmental gradient, such as ecotones where the spatial pattern becomes central to facilitation.

  16. How the strengths of Lisp-family languages facilitate building complex and flexible bioinformatics applications.

    PubMed

    Khomtchouk, Bohdan B; Weitz, Edmund; Karp, Peter D; Wahlestedt, Claes

    2016-12-31

    We present a rationale for expanding the presence of the Lisp family of programming languages in bioinformatics and computational biology research. Put simply, Lisp-family languages enable programmers to more quickly write programs that run faster than in other languages. Languages such as Common Lisp, Scheme and Clojure facilitate the creation of powerful and flexible software that is required for complex and rapidly evolving domains like biology. We will point out several important key features that distinguish languages of the Lisp family from other programming languages, and we will explain how these features can aid researchers in becoming more productive and creating better code. We will also show how these features make these languages ideal tools for artificial intelligence and machine learning applications. We will specifically stress the advantages of domain-specific languages (DSLs): languages that are specialized to a particular area, and thus not only facilitate easier research problem formulation, but also aid in the establishment of standards and best programming practices as applied to the specific research field at hand. DSLs are particularly easy to build in Common Lisp, the most comprehensive Lisp dialect, which is commonly referred to as the 'programmable programming language'. We are convinced that Lisp grants programmers unprecedented power to build increasingly sophisticated artificial intelligence systems that may ultimately transform machine learning and artificial intelligence research in bioinformatics and computational biology.

  17. A Facilitated Peer Mentoring Program for Junior Faculty to Promote Professional Development and Peer Networking

    PubMed Central

    Fleming, Geoffrey M.; Simmons, Jill H.; Xu, Meng; Gesell, Sabina B.; Brown, Rebekah F.; Cutrer, William B.; Gigante, Joseph; Cooper, William O.

    2015-01-01

    Purpose To explore the design, implementation, and efficacy of a faculty development program in a cohort of early-career junior faculty. Method Interested junior faculty members were divided into interdisciplinary small groups led by senior faculty facilitators. The groups met monthly for 1.5 hours to review a modular curriculum from 2011 to 2013. Using a survey at two time points (September 2011 and May 2013) and an interim program evaluation, the authors collected data on participants’ demographics, faculty interconnectedness, and self-reported knowledge, skills, and attitudes (KSA) in the domains of professional development and scholarship, including the ability to write career goals and align activities with those goals. Results A total of 104 junior faculty participated in the program. They demonstrated changes in self-reported KSA in the domains of professional development (P = .013, P = .001) and scholarship (P = .038, P = .015) with an increase in ability to write career goals (P < .001), align activities with those goals (P < .001), and in the number of and amount of time spent pursuing activities related to those goals (P = .022). These changes were more significant among female faculty and were not affected by academic rank or time since last training. Interconnectedness among faculty increased during the period of study--the number of nodes and ties between nodes within the network increased. Conclusions This facilitated peer mentoring program for junior faculty was effective in improving the KSA necessary to promote early career advancement and peer networking, especially for women. PMID:25830537

  18. Dynamics and Adaptive Benefits of Protein Domain Emergence and Arrangements during Plant Genome Evolution

    PubMed Central

    Kersting, Anna R.; Bornberg-Bauer, Erich; Moore, Andrew D.; Grath, Sonja

    2012-01-01

    Plant genomes are generally very large, mostly paleopolyploid, and have numerous gene duplicates and complex genomic features such as repeats and transposable elements. Many of these features have been hypothesized to enable plants, which cannot easily escape environmental challenges, to rapidly adapt. Another mechanism, which has recently been well described as a major facilitator of rapid adaptation in bacteria, animals, and fungi but not yet for plants, is modular rearrangement of protein-coding genes. Due to the high precision of profile-based methods, rearrangements can be well captured at the protein level by characterizing the emergence, loss, and rearrangements of protein domains, their structural, functional, and evolutionary building blocks. Here, we study the dynamics of domain rearrangements and explore their adaptive benefit in 27 plant and 3 algal genomes. We use a phylogenomic approach by which we can explain the formation of 88% of all arrangements by single-step events, such as fusion, fission, and terminal loss of domains. We find many domains are lost along every lineage, but at least 500 domains are novel, that is, they are unique to green plants and emerged more or less recently. These novel domains duplicate and rearrange more readily within their genomes than ancient domains and are overproportionally involved in stress response and developmental innovations. Novel domains more often affect regulatory proteins and show a higher degree of structural disorder than ancient domains. Whereas a relatively large and well-conserved core set of single-domain proteins exists, long multi-domain arrangements tend to be species-specific. We find that duplicated genes are more often involved in rearrangements. Although fission events typically impact metabolic proteins, fusion events often create new signaling proteins essential for environmental sensing. Taken together, the high volatility of single domains and complex arrangements in plant genomes

  19. 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…

  20. A grid to facilitate physics staffing justification.

    PubMed

    Klein, Eric E

    2009-12-03

    Justification of clinical physics staffing levels is difficult due to the lack of direction as how to equate clinical needs with the staffing levels and competency required. When a physicist negotiates staffing requests to administration, she/he often refers to American College of Radiology staffing level suggestions, and resources such as the Abt studies. This approach is often met with questions as to how to fairly derive the time it takes to perform tasks. The result is often insufficient and/or inexperienced staff handling complex and cumbersome tasks. We undertook development of a staffing justification grid to equate the clinical needs to the quantity and quality of staffing required. The first step is using the Abt study, customized to the clinical setting, to derive time per task multiplied by the anticipated number of such tasks. Inclusion of vacation, meeting, and developmental time may be incorporated along with allocated time for education and administration. This is followed by mapping the tasks to the level of competency/experience needed. For example, in an academic setting the faculty appointment levels correlate with experience. Non-staff personnel, such as IMRT QA technicians or clerical staff, should also be part of the equation. By using the staffing justification grid, we derived strong documentation to justify a substantial budget increase. The grid also proved useful when our clinical demands changed. Justification for physics staffing can be significantly strengthened with a properly developed data-based time and work analysis. A staffing grid is presented, along with a development methodology that facilitated our justification. Though our grid is for a large academic facility, the methodology can be extended to a non-academic setting, and to a smaller scale. This grid method not only equates the clinical needs with the quantity of staffing, but can also help generate the personnel budget, based on the type of staff and personnel required

  1. CNK and HYP form a discrete dimer by their SAM domains to mediate RAF kinase signaling.

    PubMed

    Rajakulendran, Thanashan; Sahmi, Malha; Kurinov, Igor; Tyers, Mike; Therrien, Marc; Sicheri, Frank

    2008-02-26

    RAF kinase functions in the mitogen-activated protein kinase (MAPK) pathway to transmit growth signals to the downstream kinases MEK and ERK. Activation of RAF catalytic activity is facilitated by a regulatory complex comprising the proteins CNK (Connector enhancer of KSR), HYP (Hyphen), and KSR (Kinase Suppressor of Ras). The sterile alpha-motif (SAM) domain found in both CNK and HYP plays an essential role in complex formation. Here, we have determined the x-ray crystal structure of the SAM domain of CNK in complex with the SAM domain of HYP. The structure reveals a single-junction SAM domain dimer of 1:1 stoichiometry in which the binding mode is a variation of polymeric SAM domain interactions. Through in vitro and in vivo mutational analyses, we show that the specific mode of dimerization revealed by the crystal structure is essential for RAF signaling and facilitates the recruitment of KSR to form the CNK/HYP/KSR regulatory complex. We present two docking-site models to account for how SAM domain dimerization might influence the formation of a higher-order CNK/HYP/KSR complex.

  2. Cellulose binding domain fusion proteins

    SciTech Connect

    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.

  3. 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…

  4. 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.

  5. Impact of Domain Analysis on Reuse Methods

    DTIC Science & Technology

    1989-11-06

    libraries with very different domain models . The semantic network knowledge representation system (differing in this respect from object-oriented approaches...2.1.4 Organizational Strategies ...... ............. 10 2.1.5 Role of Existing Systems ..... .............. ..11 2.2 Process Models for Domain Analysis...Acquire Domain Analysis Resources. ... 15 2.2.4 Develop the Domain Model ..... .............. .16 2.2.4.1 Identification of Domain Objects

  6. Facilitating Soldier Receipt of Needed Mental Health Treatment

    DTIC Science & Technology

    2016-01-01

    AWARD NUMBER: W81XWH-11-2-0010 TITLE: Facilitating Soldier Receipt of Needed Mental Health Treatment PRINCIPAL INVESTIGATOR: Thomas W. Britt...SUBTITLE Facilitating Soldier Receipt of Needed Mental Health Treatment Sa. CONTRACT NUMBER Sb. GRANT NUMBER W81XWH-11-2-0010 Sc. PROGRAM ELEMENT...the final version of the ’’Facilitating Mental Health Treatment (FMHT)" unit and leader training, gaining Institutional Review Board (and MRMC

  7. Structure of the Response Regulator PhoP from Mycobacterium tuberculosis Reveals a Dimer Through the Receiver Domain

    SciTech Connect

    S Menon; S Wang

    2011-12-31

    The PhoP protein from Mycobacterium tuberculosis is a response regulator of the OmpR/PhoB subfamily, whose structure consists of an N-terminal receiver domain and a C-terminal DNA-binding domain. How the DNA-binding activities are regulated by phosphorylation of the receiver domain remains unclear due to a lack of structural information on the full-length proteins. Here we report the crystal structure of the full-length PhoP of M. tuberculosis. Unlike other known structures of full-length proteins of the same subfamily, PhoP forms a dimer through its receiver domain with the dimer interface involving {alpha}4-{beta}5-{alpha}5, a common interface for activated receiver domain dimers. However, the switch residues, Thr99 and Tyr118, are in a conformation resembling those of nonactivated receiver domains. The Tyr118 side chain is involved in the dimer interface interactions. The receiver domain is tethered to the DNA-binding domain through a flexible linker and does not impose structural constraints on the DNA-binding domain. This structure suggests that phosphorylation likely facilitates/stabilizes receiver domain dimerization, bringing the DNA-binding domains to close proximity, thereby increasing their binding affinity for direct repeat DNA sequences.

  8. Sprouty 2 binds ESCRT-II factor Eap20 and facilitates HIV-1 gag release.

    PubMed

    Medina, G N; Ehrlich, L S; Chen, M H; Khan, M B; Powell, M D; Carter, C A

    2011-07-01

    The four ESCRT (endocytic sorting complexes required for transport) complexes (ESCRT-0, -I, -II, and -III) normally operate sequentially in the trafficking of cellular cargo. HIV-1 Gag trafficking and release as virus-like particles (VLPs) require the participation of ESCRTs; however, its use of ESCRTs is selective and nonsequential. Specifically, Gag trafficking to release sites on the plasma membrane does not require ESCRT-0 or -II. It is known that a bypass of ESCRT-0 is achieved by the direct linkage of the ESCRT-I component, Tsg101, to the primary L domain motif (PTAP) in Gag and that bypass of ESCRT-II is achieved by the linkage of Gag to ESCRT-III through the adaptor protein Alix. However, the mechanism by which Gag suppresses the interaction of bound ESCRT-I with ESCRT-II is unknown. Here we show (i) that VLP release requires the steady-state level of Sprouty 2 (Spry2) in COS-1 cells, (ii) that Spry2 binds the ESCRT-II component Eap20, (iii) that binding Eap20 permits Spry2 to disrupt ESCRT-I interaction with ESCRT-II, and (iv) that coexpression of Gag with a Spry2 fragment that binds Eap20 increases VLP release. Spry2 also facilitated release of P7L-Gag (i.e., release in the absence of Tsg101 binding). In this case, rescue required the secondary L domain (YPX(n)L) in HIV-1 Gag that binds Alix and the region in Spry2 that binds Eap20. The results identify Spry2 as a novel cellular factor that facilitates release driven by the primary and secondary HIV-1 Gag L domains.

  9. Enhancement of Local Photovoltaic Current at Ferroelectric Domain Walls in BiFeO3

    PubMed Central

    Yang, Ming-Min; Bhatnagar, Akash; Luo, Zheng-Dong; Alexe, Marin

    2017-01-01

    Domain walls, which are intrinsically two dimensional nano-objects exhibiting nontrivial electronic and magnetic behaviours, have been proven to play a crucial role in photovoltaic properties of ferroelectrics. Despite this recognition, the electronic properties of domain walls under illumination until now have been accessible only to macroscopic studies and their effects upon the conduction of photovoltaic current still remain elusive. The lack of understanding hinders the developing of nanoscale devices based on ferroelectric domain walls. Here, we directly characterize the local photovoltaic and photoconductive properties of 71° domain walls on BiFeO3 thin films with a nanoscale resolution. Local photovoltaic current, proven to be driven by the bulk photovoltaic effect, has been probed over the whole illuminated surface by using a specially designed photoelectric atomic force microscopy and found to be significantly enhanced at domain walls. Additionally, spatially resolved photoconductive current distribution reveals a higher density of excited carriers at domain walls in comparison with domains. Our measurements demonstrate that domain wall enhanced photovoltaic current originates from its high conduction rather than the internal electric field. This photoconduction facilitated local photovoltaic current is likely to be a universal property of topological defects in ferroelectric semiconductors. PMID:28216672

  10. Nucleoporin domain topology is linked to the transport status of the nuclear pore complex.

    PubMed

    Paulillo, Sara M; Phillips, Erica M; Köser, Joachim; Sauder, Ursula; Ullman, Katharine S; Powers, Maureen A; Fahrenkrog, Birthe

    2005-08-26

    Nuclear pore complexes (NPCs) facilitate macromolecular exchange between the nucleus and cytoplasm of eukaryotic cells. The vertebrate NPC is composed of approximately 30 different proteins (nucleoporins), of which around one third contain phenylalanine-glycine (FG)-repeat domains that are thought to mediate the main interaction between the NPC and soluble transport receptors. We have recently shown that the FG-repeat domain of Nup153 is flexible within the NPC, although this nucleoporin is anchored to the nuclear side of the NPC. By using domain-specific antibodies, we have now mapped the domain topology of Nup214 in Xenopus oocytes and in human somatic cells by immuno-EM. We have found that whereas Nup214 is anchored to the cytoplasmic side of the NPC via its N-terminal and central domain, its FG-repeat domain appears flexible, residing on both sides of the NPC. Moreover, the spatial distribution of the FG-repeat domains of both Nup153 and Nup214 shifts in a transport-dependent manner, suggesting that the location of FG-repeat domains within the NPC correlates with cargo/receptor interactions and that they concomitantly move with cargo through the central pore of the NPC.

  11. Efficient secretion of a folded protein domain by a monomeric bacterial autotransporter.

    PubMed

    Skillman, Kristen M; Barnard, Travis J; Peterson, Janine H; Ghirlando, Rodolfo; Bernstein, Harris D

    2005-11-01

    Bacterial autotransporters are proteins that contain a small C-terminal 'beta domain' that facilitates translocation of a large N-terminal 'passenger domain' across the outer membrane (OM) by an unknown mechanism. Here we used EspP, an autotransporter produced by Escherichia coli 0157:H7, as a model protein to gain insight into the transport reaction. Initially we found that the passenger domain of a truncated version of EspP (EspPDelta1-851) was translocated efficiently across the OM. Blue Native polyacrylamide gel electrophoresis, analytical ultracentrifugation and other biochemical methods showed that EspPDelta1-851 behaves as a compact monomer and strongly suggest that the channel formed by the beta domain is too narrow to accommodate folded polypeptides. Surprisingly, we found that a folded protein domain fused to the N-terminus of EspPDelta1-851 was efficiently translocated across the OM. Further analysis revealed that the passenger domain of wild-type EspP also folds at least partially in the periplasm. To reconcile these data, we propose that the EspP beta domain functions primarily to target and anchor the protein and that an external factor transports the passenger domain across the OM.

  12. Enhancement of Local Photovoltaic Current at Ferroelectric Domain Walls in BiFeO3.

    PubMed

    Yang, Ming-Min; Bhatnagar, Akash; Luo, Zheng-Dong; Alexe, Marin

    2017-02-20

    Domain walls, which are intrinsically two dimensional nano-objects exhibiting nontrivial electronic and magnetic behaviours, have been proven to play a crucial role in photovoltaic properties of ferroelectrics. Despite this recognition, the electronic properties of domain walls under illumination until now have been accessible only to macroscopic studies and their effects upon the conduction of photovoltaic current still remain elusive. The lack of understanding hinders the developing of nanoscale devices based on ferroelectric domain walls. Here, we directly characterize the local photovoltaic and photoconductive properties of 71° domain walls on BiFeO3 thin films with a nanoscale resolution. Local photovoltaic current, proven to be driven by the bulk photovoltaic effect, has been probed over the whole illuminated surface by using a specially designed photoelectric atomic force microscopy and found to be significantly enhanced at domain walls. Additionally, spatially resolved photoconductive current distribution reveals a higher density of excited carriers at domain walls in comparison with domains. Our measurements demonstrate that domain wall enhanced photovoltaic current originates from its high conduction rather than the internal electric field. This photoconduction facilitated local photovoltaic current is likely to be a universal property of topological defects in ferroelectric semiconductors.

  13. Enhancement of Local Photovoltaic Current at Ferroelectric Domain Walls in BiFeO3

    NASA Astrophysics Data System (ADS)

    Yang, Ming-Min; Bhatnagar, Akash; Luo, Zheng-Dong; Alexe, Marin

    2017-02-01

    Domain walls, which are intrinsically two dimensional nano-objects exhibiting nontrivial electronic and magnetic behaviours, have been proven to play a crucial role in photovoltaic properties of ferroelectrics. Despite this recognition, the electronic properties of domain walls under illumination until now have been accessible only to macroscopic studies and their effects upon the conduction of photovoltaic current still remain elusive. The lack of understanding hinders the developing of nanoscale devices based on ferroelectric domain walls. Here, we directly characterize the local photovoltaic and photoconductive properties of 71° domain walls on BiFeO3 thin films with a nanoscale resolution. Local photovoltaic current, proven to be driven by the bulk photovoltaic effect, has been probed over the whole illuminated surface by using a specially designed photoelectric atomic force microscopy and found to be significantly enhanced at domain walls. Additionally, spatially resolved photoconductive current distribution reveals a higher density of excited carriers at domain walls in comparison with domains. Our measurements demonstrate that domain wall enhanced photovoltaic current originates from its high conduction rather than the internal electric field. This photoconduction facilitated local photovoltaic current is likely to be a universal property of topological defects in ferroelectric semiconductors.

  14. Evidence for general and domain-specific elements of teacher-child interactions: associations with preschool children's development.

    PubMed

    Hamre, Bridget; Hatfield, Bridget; Pianta, Robert; Jamil, Faiza

    2014-01-01

    This study evaluates a model for considering domain-general and domain-specific associations between teacher-child interactions and children's development, using a bifactor analytic strategy. Among a sample of 325 early childhood classrooms there was evidence for both general elements of teacher-child interaction (responsive teaching) and domain-specific elements related to positive management and routines and cognitive facilitation. Among a diverse population of 4-year-old children (n = 1,407) responsive teaching was modestly associated with development across social and cognitive domains, whereas positive management and routines was modestly associated with increases in inhibitory control and cognitive facilitation was associated with gains in early language and literacy skills. The conceptual and methodological contributions and challenges of this approach are discussed.

  15. Crystal Structure of the Dimeric Oct6 (Pou3fl) POU Domain Bound to Palindromic MORE DNA

    SciTech Connect

    R Jauch; S Choo; C Ng; P Kolatkar

    2011-12-31

    POU domains (named after their identification in Pit1, Oct1 unc86) are found in around 15 transcription factors encoded in mammalian genomes many of which feature prominently as key regulators at development bifurcations. For example, the POU III class Octamer binding protein 6 (Oct6) is expressed in embryonic stem cells and during neural development and drives the differentia5tion of myelinated cells in the central and peripheral nervous system. Defects in oct6 expression levels are linked to neurological disorders such as schizophrenia. POU proteins contain a bi-partite DNA binding domain that assembles on various DNA motifs with differentially configured subdomains. Intriguingly, alternative configurations of POU domains on different DNA sites were shown to affect the subsequent recruitment of transcriptional coactivators. Namely, binding of Oct1 to a Palindromic Oct-factor Recognition Element (PORE) was shown to facilitate the recruitment of the OBF1 coactivator whereas More of PORE (MORE) bound Oct1 does not. Moreover, Pit1 was shown to recruit the corepressor N-CoR only when bound to a variant MORE motif with a 2 bp half-site spacing. Therefore, POU proteins are seen as a paradigm for DNA induced allosteric effects on transcription factors modulating their regulatory potential. However, a big unresolved conundrum for the POU class and for most if not all other transcription factor classes is how highly similar proteins regulate different sets of genes causing fundamentally different biological responses. Ultimately, there must be subtle features enabling those factors to engage in contrasting molecular interactions in the cell. Thus, the dissection of the molecular details of the transcription-DNA recognition in general, and the formation of multimeric regulatory complexes, in particular, is highly desirable. To contribute to these efforts they solved the 2.05 {angstrom} crystal structure of Oct6 bound as a symmetrical homodimer to palindromic MORE DNA.

  16. Protein Interaction between Ameloblastin and Proteasome Subunit α Type 3 Can Facilitate Redistribution of Ameloblastin Domains within Forming Enamel.

    PubMed

    Geng, Shuhui; White, Shane N; Paine, Michael L; Snead, Malcolm L

    2015-08-21

    Enamel is a bioceramic tissue composed of thousands of hydroxyapatite crystallites aligned in parallel within boundaries fabricated by a single ameloblast cell. Enamel is the hardest tissue in the vertebrate body; however, it starts development as a self-organizing assembly of matrix proteins that control crystallite habit. Here, we examine ameloblastin, a protein that is initially distributed uniformly across the cell boundary but redistributes to the lateral margins of the extracellular matrix following secretion thus producing cell-defined boundaries within the matrix and the mineral phase. The yeast two-hybrid assay identified that proteasome subunit α type 3 (Psma3) interacts with ameloblastin. Confocal microscopy confirmed Psma3 co-distribution with ameloblastin at the ameloblast secretory end piece. Co-immunoprecipitation assay of mouse ameloblast cell lysates with either ameloblastin or Psma3 antibody identified each reciprocal protein partner. Protein engineering demonstrated that only the ameloblastin C terminus interacts with Psma3. We show that 20S proteasome digestion of ameloblastin in vitro generates an N-terminal cleavage fragment consistent with the in vivo pattern of ameloblastin distribution. These findings suggest a novel pathway participating in control of protein distribution within the extracellular space that serves to regulate the protein-mineral interactions essential to biomineralization.

  17. Effects of amino acid mutations in the pore-forming domain of the hemolytic lectin CEL-III.

    PubMed

    Nagao, Tomonao; Masaki, Risa; Unno, Hideaki; Goda, Shuichiro; Hatakeyama, Tomomitsu

    2016-10-01

    The hemolytic lectin CEL-III forms transmembrane pores in the membranes of target cells. A study on the effect of site-directed mutation at Lys405 in domain 3 of CEL-III indicated that replacements of this residue by relatively smaller residues lead to a marked increase in hemolytic activity, suggesting that moderately destabilizing domain 3 facilitates formation of transmembrane pores through conformational changes.

  18. Real-time investigation of referential domains in unscripted conversation: a targeted language game approach

    PubMed Central

    Brown-Schmidt, Sarah; Tanenhaus, Michael K.

    2009-01-01

    Two experiments examined the restriction of referential domains during unscripted conversation by analyzing the modification and on-line interpretation of referring expressions. Experiment 1 demonstrated that from the earliest moments of processing, addressees interpreted referring expressions with respect to referential domains constrained by the conversation. Analysis of eye movements during the conversation showed elimination of standard competition effects seen with scripted language. Results from Experiment 2 pinpointed two pragmatic factors responsible for restriction of the referential domains used by speakers to design referential expressions and demonstrated that the same factors predict whether addressees consider local competitors to be potential referents during on-line interpretation of the same expressions. These experiments demonstrate for the first time that on-line interpretation of referring expressions in conversation is facilitated by referential domains constrained by pragmatic factors which predict when addressees are likely to encounter temporary ambiguity in language processing. PMID:19890480

  19. 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

  20. 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.

  1. 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.

  2. Domain Processes in Ferroelectric Ceramics

    DTIC Science & Technology

    1994-04-14

    WALLS Electron holography utilizing the wave characteristics of electrons. Through a sharp emission tip, the emitted electron beam is largely coherent, or...mirostructural modulation at 25% doping. The strongly first order ferroelectric phase transition in PbTiO3 is also gradually changed to a nearly second...a new domain configuraton. 13 The end-member of the PZT solid solution, PbTiO3 , has the highest transition temperature (Tc = 490 °C) and the largest

  3. Dynamic optical frequency domain reflectometry.

    PubMed

    Arbel, Dror; Eyal, Avishay

    2014-04-21

    We describe a dynamic Optical Frequency Domain Reflectometry (OFDR) system which enables real time, long range, acoustic sensing at high sampling rate. The system is based on a fast scanning laser and coherent detection scheme. Distributed sensing is obtained by probing the Rayleigh backscattered light. The system was tested by interrogation of a 10 km communication type single mode fiber and successfully detected localized impulse and sinusoidal excitations.

  4. L2 Gender Facilitation and Inhibition in Spoken Word Recognition

    ERIC Educational Resources Information Center

    Behney, Jennifer N.

    2011-01-01

    This dissertation investigates the role of grammatical gender facilitation and inhibition in second language (L2) learners' spoken word recognition. Native speakers of languages that have grammatical gender are sensitive to gender marking when hearing and recognizing a word. Gender facilitation refers to when a given noun that is preceded by an…

  5. 50 CFR 300.5 - Facilitation of enforcement.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 7 2010-10-01 2010-10-01 false Facilitation of enforcement. 300.5 Section 300.5 Wildlife and Fisheries INTERNATIONAL FISHING AND RELATED ACTIVITIES INTERNATIONAL FISHERIES REGULATIONS General § 300.5 Facilitation of enforcement. (a) Compliance. The operator of, or any other...

  6. The Principal as a Catalyst and Facilitator of Planned Change.

    ERIC Educational Resources Information Center

    Chamley, John; And Others

    1994-01-01

    Educational change must be facilitated, not dictated, to be successful. Since most new curriculum programs ignore complex classroom realities, teachers usually view them negatively. Facilitative principals create the necessary conditions for change by progressing through three stages: creating new roles and expectations, mobilizing proponents for…

  7. Facilitated transport of copper with hydroxyapatite nanoparticles in saturated sand

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Saturated packed column experiments were conducted to investigate the facilitated transport of Cu with hydroxyapatite nanoparticles (nHAP) at different pore water velocities (0.22-2.2 cm min–1), solution pH (6.2-9.0), and fraction of Fe oxide coating on grain surfaces (', 0-0.36). The facilitated tr...

  8. The New England School Effectiveness Project: A Facilitator's Sourcebook.

    ERIC Educational Resources Information Center

    Northeast Regional Exchange, Inc., Chelmsford, MA.

    The School Team Facilitator assists participating New England secondary schools in planning and implementing improvement efforts based on school effectiveness research. This publication, distributed at a team training conference, begins with the conference schedule, a list of facilitators, instructions on choosing a school team, and letters to…

  9. "Just Add Facilitators and Stir": Stimulating Policy Uptake in Schools

    ERIC Educational Resources Information Center

    Abbott, Rebecca; Macdonald, Doune; Hay, Peter; McCuaig, Louise

    2011-01-01

    This article presents the evaluation findings of an education policy initiative that involved the employment of facilitators to broker the policy and its implementation. An Australian state's education authority piloted the employment of physical activity facilitators to expedite the implementation of "Smart Moves" in schools, a…

  10. A Facilitator Guide. Outdoor Education for the Handicapped.

    ERIC Educational Resources Information Center

    Kentucky Univ., Lexington.

    The concept and purpose of this facilitator guide is to provide the three facilitator groups of educators, park and resource management personnel, and parents of handicapped children with information on how to cooperatively design and implement an outdoor education program for handicapped students. Chapter 1 (contributed by Vicki Stayton) outlines…

  11. 50 CFR 600.752 - Use of conveners and facilitators.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... issues of concern, and to ascertain whether the establishment of an FNP regarding such matter is feasible... an impartial, neutral facilitator for the negotiations of the FNP, subject to the approval of the FNP... section. If the FNP does not approve the nominee of the Council or NMFS for facilitator, the FNP...

  12. Exploring Dimensions of Critical Reflection in Activist-Facilitator Practice

    ERIC Educational Resources Information Center

    Hanson, Cindy

    2013-01-01

    This article explores how 14 diverse, Canadian activist-facilitators working in international development experience and understand "critical reflection" as a component of participatory methodologies in facilitation practices. The findings, based on my doctoral study, demonstrate that although critical reflection is often discussed as…

  13. Facilitating North-South Partnerships for Sustainable Agriculture

    ERIC Educational Resources Information Center

    Termeer, C. J. A. M.; Hilhorst, T.; Oorthuizen, J.

    2010-01-01

    The increased number of development cooperation and sustainable agriculture partnerships brings with it new challenges for professionals who are asked to facilitate these partnering processes. In this article we shed more light on the world of development cooperation and we explore questions that facilitators working with North-South partnerships…

  14. The Facilitator's Edge: Group Sessions for Edge-ucators.

    ERIC Educational Resources Information Center

    Handcock, Helen

    The Facilitator's Edge is a workshop series based on the life/work messages of The Edge magazine. The workshops are deigned to help educators, youth workers, and their career practitioners facilitate conscious career building. This manual consists of five group sessions, each focusing on a different career-building theme. "Megatrends and…

  15. Connectivity of Learning in MOOCs: Facilitators' Experiences in Team Teaching

    ERIC Educational Resources Information Center

    Mercado-Varela, Martin Alonso; Beltran, Jesus; Perez, Marisol Villegas; Vazquez, Nohemi Rivera; Ramirez-Montoya, Maria-Soledad

    2017-01-01

    The role of facilitators in distance learning environments is of substantial importance in supporting the learning process. This article specifically discusses the role of the facilitator in Massive Open Online Courses (MOOC), which are characterized by their stimulation of learning connections. The study analyzes the experiences of 135…

  16. Drug-Facilitated Sexual Assault on Campus: Challenges and Interventions.

    ERIC Educational Resources Information Center

    Hensley, Laura G.

    2002-01-01

    The use of gamma-hydroxybutyric acid (GHB) to facilitate sexual assault is increasing on campuses nationwide. This article provides college counselors with an overview of the use of GHB in campus sexual assault, outlines suggestions for crisis intervention, and discusses the challenges of counseling survivors of drug-facilitated sexual assault.…

  17. Orthographic Facilitation Effects on Spoken Word Production: Evidence from Chinese

    ERIC Educational Resources Information Center

    Zhang, Qingfang; Weekes, Brendan Stuart

    2009-01-01

    The aim of this experiment was to investigate the time course of orthographic facilitation on picture naming in Chinese. We used a picture-word paradigm to investigate orthographic and phonological facilitation on monosyllabic spoken word production in native Mandarin speakers. Both the stimulus-onset asynchrony (SOA) and the picture-word…

  18. 31 CFR 537.418 - Facilitating new investment.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 31 Money and Finance:Treasury 3 2014-07-01 2014-07-01 false Facilitating new investment. 537.418 Section 537.418 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE... § 537.418 Facilitating new investment. Consistent with § 537.530, U.S. persons may approve,...

  19. An Analysis of Instructional Facilitators' Relationships with Teachers and Principals

    ERIC Educational Resources Information Center

    Range, Bret G.; Pijanowski, John C.; Duncan, Heather; Scherz, Susan; Hvidston, David

    2014-01-01

    This study examines the perspectives of Wyoming instructional facilitators, concerning three coaching constructs--namely, their instructional leadership roles, teachers' instructional practices, and the support that they receive from principals and teachers. Findings suggest that instructional facilitators were positive about their instructional…

  20. Self-Motivated Personal Career Planning Program. Facilitator's Guide.

    ERIC Educational Resources Information Center

    Walter, Verne; Wallace, Melvin

    The guide presents a process of self-assessment and goal-setting involving employee planners and management facilitators. An overview and rationale of the program and instructions and procedures are discussed in Chapters 1 and 2. Chapter 3 deals with effective facilitator skills and procedural steps for self-assessment, comparison with others, and…

  1. The Relationship of Facilitative Functioning to Effective Peer Supervision

    ERIC Educational Resources Information Center

    Seligman, Linda

    1978-01-01

    This study investigates peer supervision. The criterion used was counselor trainees' growth in facilitative functioning. The study sought to ascertain whether the facilitative counselor trainee was also the effective peer supervisor, to provide information on evaluating peer-supervisory experience, and to shed light on the most effective…

  2. Barriers to and Facilitators of Health for Latina Undergraduate Students

    ERIC Educational Resources Information Center

    Mount, Jill

    2015-01-01

    Latina undergraduate students' barriers and facilitators of health are examined: Barriers to psychological health--separating from family, pressure to succeed, and racism; Barriers to physical health--lacking health insurance, and discomfort using campus sports facilities; and Facilitators of psychological health--membership in Latina student…

  3. Computation Of Facilitated Transport of O2 In Hemoglobin

    NASA Technical Reports Server (NTRS)

    Davis, Sanford

    1991-01-01

    Report describes computations of unsteady facilitated transport of oxygen through liquid membrane of hemoglobin. Used here, "facilitated transport" means diffusion of permeant through membrane in which that diffusion enhanced by reversible chemical reaction between permeant and membrane. In this case, reversible reactions between hemoglobin and oxygen.

  4. Using Text Mining to Characterize Online Discussion Facilitation

    ERIC Educational Resources Information Center

    Ming, Norma; Baumer, Eric

    2011-01-01

    Facilitating class discussions effectively is a critical yet challenging component of instruction, particularly in online environments where student and faculty interaction is limited. Our goals in this research were to identify facilitation strategies that encourage productive discussion, and to explore text mining techniques that can help…

  5. Evidence for rotational contribution to protein-facilitated proton transport.

    PubMed Central

    Gros, G; Lavalette, D; Moll, W; Gros, H; Amand, B; Pochon, F

    1984-01-01

    Two modes of molecular motion of carrier molecules can, in principle, lead to a facilitated transport of a substrate: translational and rotational diffusion. In the present study, which deals with the mechanism of the facilitated diffusion of H+ and O2 in solutions of earthworm hemoglobin, examples for both types of facilitation are presented. Only translational, not rotational, diffusion of earthworm hemoglobin appears to lead to a facilitated O2 flux. In contrast, substantial facilitated H+ fluxes of comparable size arise from rotational diffusion as well as from translational diffusion of this large protein. This is derived from measurements of facilitated H+ and O2 fluxes in earthworm hemoglobin solutions and determinations of the rotational and translational diffusion coefficients of earthworm hemoglobin with the help of a theoretical treatment of facilitated diffusion by rotational carrier diffusion. H+ transport by rotational protein diffusion appears to be a case where the often-postulated mechanism of facilitated transport by rotation of a carrier lends itself to experimental verification. Images PMID:6324213

  6. Team Building. Baldor Electric Company. [Facilitator Guide and Participant Guide.

    ERIC Educational Resources Information Center

    Saint Louis Community Coll., MO. Workplace Literacy Services Center.

    This document contains the facilitator and participant guides for a course in team building that was developed by a community college for a St. Louis (Missouri) electric company. The facilitator's guide contains the transparency masters, outlines, learning activities, questionnaires, and other handouts required for two course sessions. The first…

  7. Facilitated Communication and Its Legitimacy--Twenty-First Century Developments

    ERIC Educational Resources Information Center

    Mostert, Mark P.

    2010-01-01

    By 2001, Facilitated Communication (FC) had largely been empirically discredited as an effective intervention for previously uncommunicative persons with disabilities, especially those with autism and related disorders. Key empirical findings consistently showed that the facilitator and not the client initiated communication. I analyze the extant…

  8. Applications of Motivational Interviewing in Career Counseling: Facilitating Career Transition

    ERIC Educational Resources Information Center

    Stoltz, Kevin B.; Young, Tabitha L.

    2013-01-01

    The Protean and Boundaryless career paradigms are calling for new ways to provide career counseling to clients. Career counselors need methods for facilitating client's career transition across all stages of career development. This facilitation requires career counselors to be armed with methods for promoting client's autonomy,…

  9. Partners in Quality: Facilitator's Guide = Partenaires Pour la Qualite.

    ERIC Educational Resources Information Center

    Beckman, Sandra

    Partners in Quality is a research and development project sponsored by the Canadian Child Care Federation and its affiliates to explore how child care providers, parents, and other partners can work together to support and improve quality in child care. This facilitator's guide is designed to help facilitators prepare and deliver workshops based…

  10. Subharmonic Fourier domain mode locking.

    PubMed

    Eigenwillig, Christoph M; Wieser, Wolfgang; Biedermann, Benjamin R; Huber, Robert

    2009-03-15

    We demonstrate a subharmonically Fourier domain mode-locked wavelength-swept laser source with a substantially reduced cavity fiber length. In contrast to a standard Fourier domain mode-locked configuration, light is recirculated repetitively in the delay line with the optical bandpass filter used as switch. The laser has a fundamental optical round trip frequency of 285 kHz and can be operated at integer fractions thereof (subharmonics). Sweep ranges up to 95 nm full width centred at 1317 nm are achieved at the 1/5th subharmonic. A maximum sensitivity of 116 dB and an axial resolution of 12 microm in air are measured at an average sweep power of 12 mW. A sensitivity roll-off of 11 dB over 4 mm and 25 dB over 10 mm is observed and optical coherence tomography imaging is demonstrated. Besides the advantage of a reduced fiber length, subharmonic Fourier domain mode locking (shFDML) enables simple scaling of the sweep speed by extracting light from the delay part of the resonator. A sweep rate of 570 kHz is achieved. Characteristic features of shFDML operation, such as power leakage during fly-back and cw breakthrough, are investigated.

  11. Cross-Domain Network Fault Localization

    DTIC Science & Technology

    2009-06-01

    digest, or simply digest, for Gi. • Gj = ( n ] i6=j f(Gi) ) ] Gj , where j is a domain performing cross-domain inference and ] is a model-specific union... Gj is the cross-domain model integrating the digests from all the other domains with domain j’s undigested graph. Now, domain j may use an existing...algorithm such as SHRINK to perform inference over Gj . Before a practical graph digest design can be implemented, interoperability standards must be

  12. Joint annotation of chromatin state and chromatin conformation reveals relationships among domain types and identifies domains of cell-type-specific expression.

    PubMed

    Libbrecht, Maxwell W; Ay, Ferhat; Hoffman, Michael M; Gilbert, David M; Bilmes, Jeffrey A; Noble, William Stafford

    2015-04-01

    The genomic neighborhood of a gene influences its activity, a behavior that is attributable in part to domain-scale regulation. Previous genomic studies have identified many types of regulatory domains. However, due to the difficulty of integrating genomics data sets, the relationships among these domain types are poorly understood. Semi-automated genome annotation (SAGA) algorithms facilitate human interpretation of heterogeneous collections of genomics data by simultaneously partitioning the human genome and assigning labels to the resulting genomic segments. However, existing SAGA methods cannot integrate inherently pairwise chromatin conformation data. We developed a new computational method, called graph-based regularization (GBR), for expressing a pairwise prior that encourages certain pairs of genomic loci to receive the same label in a genome annotation. We used GBR to exploit chromatin conformation information during genome annotation by encouraging positions that are close in 3D to occupy the same type of domain. Using this approach, we produced a model of chromatin domains in eight human cell types, thereby revealing the relationships among known domain types. Through this model, we identified clusters of tightly regulated genes expressed in only a small number of cell types, which we term "specific expression domains." We found that domain boundaries marked by promoters and CTCF motifs are consistent between cell types even when domain activity changes. Finally, we showed that GBR can be used to transfer information from well-studied cell types to less well-characterized cell types during genome annotation, making it possible to produce high-quality annotations of the hundreds of cell types with limited available data.

  13. Facilitator control as automatic behavior: A verbal behavior analysis

    PubMed Central

    Hall, Genae A.

    1993-01-01

    Several studies of facilitated communication have demonstrated that the facilitators were controlling and directing the typing, although they appeared to be unaware of doing so. Such results shift the focus of analysis to the facilitator's behavior and raise questions regarding the controlling variables for that behavior. This paper analyzes facilitator behavior as an instance of automatic verbal behavior, from the perspective of Skinner's (1957) book Verbal Behavior. Verbal behavior is automatic when the speaker or writer is not stimulated by the behavior at the time of emission, the behavior is not edited, the products of behavior differ from what the person would produce normally, and the behavior is attributed to an outside source. All of these characteristics appear to be present in facilitator behavior. Other variables seem to account for the thematic content of the typed messages. These variables also are discussed. PMID:22477083

  14. The neural correlates of picture naming facilitated by auditory repetition

    PubMed Central

    2012-01-01

    Background Overt repetition of auditorily presented words can facilitate picture naming performance in both unimpaired speakers and individuals with word retrieval difficulties, but the underlying neurocognitive mechanisms and longevity of such effects remain unclear. This study used functional magnetic resonance imaging to examine whether different neurological mechanisms underlie short-term (within minutes) and long-term (within days) facilitation effects from an auditory repetition task in healthy older adults. Results The behavioral results showed that both short- and long-term facilitated items were named significantly faster than unfacilitated items, with short-term items significantly faster than long-term items. Neuroimaging analyses identified a repetition suppression effect for long-term facilitated items, relative to short-term facilitated and unfacilitated items, in regions known to be associated with both semantic and phonological processing. A repetition suppression effect was also observed for short-term facilitated items when compared to unfacilitated items in a region of the inferior temporal lobe linked to semantic processing and object recognition, and a repetition enhancement effect when compared to long-term facilitated items in a posterior superior temporal region associated with phonological processing. Conclusions These findings suggest that different neurocognitive mechanisms underlie short- and long-term facilitation of picture naming by an auditory repetition task, reflecting both phonological and semantic processing. More specifically, the brain areas engaged were consistent with the view that long-term facilitation may be driven by a strengthening of semantic-phonological connections. Short-term facilitation, however, appears to result in more efficient semantic processing and/or object recognition, possibly in conjunction with active recognition of the phonological form. PMID:22364354

  15. Knowledge Discovery from Biomedical Ontologies in Cross Domains

    PubMed Central

    Shen, Feichen; Lee, Yugyung

    2016-01-01

    In recent years, there is an increasing demand for sharing and integration of medical data in biomedical research. In order to improve a health care system, it is required to support the integration of data by facilitating semantic interoperability systems and practices. Semantic interoperability is difficult to achieve in these systems as the conceptual models underlying datasets are not fully exploited. In this paper, we propose a semantic framework, called Medical Knowledge Discovery and Data Mining (MedKDD), that aims to build a topic hierarchy and serve the semantic interoperability between different ontologies. For the purpose, we fully focus on the discovery of semantic patterns about the association of relations in the heterogeneous information network representing different types of objects and relationships in multiple biological ontologies and the creation of a topic hierarchy through the analysis of the discovered patterns. These patterns are used to cluster heterogeneous information networks into a set of smaller topic graphs in a hierarchical manner and then to conduct cross domain knowledge discovery from the multiple biological ontologies. Thus, patterns made a greater contribution in the knowledge discovery across multiple ontologies. We have demonstrated the cross domain knowledge discovery in the MedKDD framework using a case study with 9 primary biological ontologies from Bio2RDF and compared it with the cross domain query processing approach, namely SLAP. We have confirmed the effectiveness of the MedKDD framework in knowledge discovery from multiple medical ontologies. PMID:27548262

  16. Cross Domain Deterrence: Livermore Technical Report, 2014-2016

    SciTech Connect

    Barnes, Peter D.; Bahney, Ben; Matarazzo, Celeste; Markey, Michael; Pearl, Jonathan

    2016-08-03

    Lawrence Livermore National Laboratory (LLNL) is an original collaborator on the project titled “Deterring Complex Threats: The Effects of Asymmetry, Interdependence, and Multi-polarity on International Strategy,” (CDD Project) led by the UC Institute on Global Conflict and Cooperation at UCSD under PIs Jon Lindsay and Erik Gartzke , and funded through the DoD Minerva Research Initiative. In addition to participating in workshops and facilitating interaction among UC social scientists, LLNL is leading the computational modeling effort and assisting with empirical case studies to probe the viability of analytic, modeling and data analysis concepts. This report summarizes LLNL work on the CDD Project to date, primarily in Project Years 1-2, corresponding to Federal fiscal year 2015. LLNL brings two unique domains of expertise to bear on this Project: (1) access to scientific expertise on the technical dimensions of emerging threat technology, and (2) high performance computing (HPC) expertise, required for analyzing the complexity of bargaining interactions in the envisioned threat models. In addition, we have a small group of researchers trained as social scientists who are intimately familiar with the International Relations research. We find that pairing simulation scientists, who are typically trained in computer science, with domain experts, social scientists in this case, is the most effective route to developing powerful new simulation tools capable of representing domain concepts accurately and answering challenging questions in the field.

  17. An Algebro-Topological Description of Protein Domain Structure

    PubMed Central

    Penner, Robert Clark; Knudsen, Michael; Wiuf, Carsten; Andersen, Jørgen Ellegaard

    2011-01-01

    The space of possible protein structures appears vast and continuous, and the relationship between primary, secondary and tertiary structure levels is complex. Protein structure comparison and classification is therefore a difficult but important task since structure is a determinant for molecular interaction and function. We introduce a novel mathematical abstraction based on geometric topology to describe protein domain structure. Using the locations of the backbone atoms and the hydrogen bonds, we build a combinatorial object – a so-called fatgraph. The description is discrete yet gives rise to a 2-dimensional mathematical surface. Thus, each protein domain corresponds to a particular mathematical surface with characteristic topological invariants, such as the genus (number of holes) and the number of boundary components. Both invariants are global fatgraph features reflecting the interconnectivity of the domain by hydrogen bonds. We introduce the notion of robust variables, that is variables that are robust towards minor changes in the structure/fatgraph, and show that the genus and the number of boundary components are robust. Further, we invesigate the distribution of different fatgraph variables and show how only four variables are capable of distinguishing different folds. We use local (secondary) and global (tertiary) fatgraph features to describe domain structures and illustrate that they are useful for classification of domains in CATH. In addition, we combine our method with two other methods thereby using primary, secondary, and tertiary structure information, and show that we can identify a large percentage of new and unclassified structures in CATH. PMID:21629687

  18. A novel domain-by-domain survivable mechanism in multi-domain wavelength-division-multiplexing optical networks

    NASA Astrophysics Data System (ADS)

    Guo, Lei; Wang, Xingwei; Li, Ying; Wang, Chongshan; Li, Hongming; Wang, Hongpeng; Liu, Xin

    2009-03-01

    In multi-domain wavelength-division-multiplexing (WDM) optical networks, the inter-domain routing is a challenge since each single-domain cannot view the full network topology. At the same time, survivability is also an important issue in optical networks since the failures of fiber links or network nodes may lead to a lot of traffic being blocked. In this paper, we study the survivability in multi-domain WDM optical networks, and propose a new survivable mechanism called load balanced domain-by-domain routing (LBDDR). In LBDDR, in order to obtain the efficient inter-domain survivable routes, we present the domain-by-domain routing (DDR) method which can find the intra-domain sub-working path and sub-backup path in each single-domain to form the inter-domain working path and backup path for each demand. In order to reduce the blocking probability, we present the load balanced routing method which can encourage the traffic to be uniformly distributed on the links with more free wavelengths. Simulation results show that, compared with conventional mechanism, LBDDR can obtain better performances.

  19. POGs2: A Web Portal to Facilitate Cross-Species Inferences About Protein Architecture and Function in Plants

    PubMed Central

    Tomcal, Michael; Stiffler, Nicholas; Barkan, Alice

    2013-01-01

    The Putative orthologous Groups 2 Database (POGs2) (http://pogs.uoregon.edu/) integrates information about the inferred proteomes of four plant species (Arabidopsis thaliana, Zea mays, Orza sativa, and Populus trichocarpa) in a display that facilitates comparisons among orthologs and extrapolation of annotations among species. A single-page view collates key functional data for members of each Putative Orthologous Group (POG): graphical representations of InterPro domains, predicted and established intracellular locations, and imported gene descriptions. The display incorporates POGs predicted by two different algorithms as well as gene trees, allowing users to evaluate the validity of POG memberships. The web interface provides ready access to sequences and alignments of POG members, as well as sequences, alignments, and domain architectures of closely-related paralogs. A simple and flexible search interface permits queries by BLAST and by any combination of gene identifier, keywords, domain names, InterPro identifiers, and intracellular location. The concurrent display of domain architectures for orthologous proteins highlights errors in gene models and false-negatives in domain predictions. The POGs2 layout is also useful for exploring candidate genes identified by transposon tagging, QTL mapping, map-based cloning, and proteomics, and for navigating between orthologous groups that belong to the same gene family. PMID:24340041

  20. Implementation of the Clinical Facilitation Model within an Australian rural setting: the role of the Clinical Facilitator.

    PubMed

    Sanderson, Helena; Lea, Jacqueline

    2012-11-01

    Education providers globally use various models for undergraduate nurse clinical education. This paper presents the major findings of a research project conducted by a rural university in Australia that aimed to explore the Clinical Facilitation Model of undergraduate nursing education from a rural perspective. In particular how the Clinical Facilitators enacted their role within the rural environment and to identify any barriers to the provision of effective clinical learning during facilitated clinical experience within this context. This qualitative study used a phenomenological approach to explore the experiences of Clinical Facilitators. Individual in-depth interviews were conducted with eight Clinical Facilitators. Data was analysed using thematic analysis and several themes emerged from the study. This paper will report two of the major findings which are based on how Clinical Facilitators enacted their role within the rural environment. Whilst this study has a rural focus the findings will add to the limited body of knowledge internationally regarding the Clinical Facilitation model used as a result of balancing educational needs of the student with the care needs of the patients in the current health policy climate. The findings will be useful for informing undergraduate curricula, and will assist faculty and health services in planning and implementation of models of clinical education that meet the needs of the student and that are specific to the rural environment. In addition, the findings will provide insight into strategies that the rural Clinical Facilitator can utilise to assist in fulfilling their teaching role.

  1. Scale-free behavior of a 2D complex plasma during rapid cooling.

    PubMed

    Knapek, C A; Durniak, C; Samsonov, D; Morfill, G E

    2013-01-18

    Experimental evidence is presented for a scale-free transition from an unordered to an ordered state in a 2D complex plasma that differs from the KTHNY theory of phase transitions in 2D systems. The transition is characterized by the formation and growth of ordered domains. A fractal relationship is found between the domain areas and domain boundary lengths, which can be explained by a recent theoretical model. The experimental findings are supported by a molecular dynamics simulation of a 2D particle system.

  2. Characterization of lipid domains in erythrocyte membranes.

    PubMed

    Rodgers, W; Glaser, M

    1991-02-15

    Fluorescence digital imaging microscopy was used to study the lateral distribution of the lipid components in erythrocyte membranes. Intact erythrocytes labeled with phospholipids containing a fluorophore attached to one fatty acid chain showed an uneven distribution of the phospholipids in the membrane thereby demonstrating the presence of membrane domains. The enrichment of the lipotropic compound chlor-promazine in domains in intact erythrocytes also suggested that the domains are lipid-enriched regions. Similar membrane domains were present in erythrocyte ghosts. The phospholipid enrichment was increased in the domains by inducing membrane protein aggregation. Double-labeling experiments were done to determine the relative distributions of different phospholipids in the membrane. Vesicles made from extracted lipids did not show the presence of domains consistent with the conclusion that membrane proteins were responsible for creating the domains. Overall, it was found that large domains exist in the red blood cell membrane with unequal enrichment of the different phospholipid species.

  3. Crystal structures of the armadillo repeat domain of adenomatous polyposis coli and its complex with the tyrosine-rich domain of Sam68.

    PubMed

    Morishita, Ella Czarina; Murayama, Kazutaka; Kato-Murayama, Miyuki; Ishizuka-Katsura, Yoshiko; Tomabechi, Yuri; Hayashi, Tomoatsu; Terada, Takaho; Handa, Noriko; Shirouzu, Mikako; Akiyama, Tetsu; Yokoyama, Shigeyuki

    2011-10-12

    Adenomatous polyposis coli (APC) is a tumor suppressor protein commonly mutated in colorectal tumors. APC plays important roles in Wnt signaling and other cellular processes. Here, we present the crystal structure of the armadillo repeat (Arm) domain of APC, which facilitates the binding of APC to various proteins. APC-Arm forms a superhelix with a positively charged groove. We also determined the structure of the complex of APC-Arm with the tyrosine-rich (YY) domain of the Src-associated in mitosis, 68 kDa protein (Sam68), which regulates TCF-1 alternative splicing. Sam68-YY forms numerous interactions with the residues on the groove and is thereby fixed in a bent conformation. We assessed the effects of mutations and phosphorylation on complex formation between APC-Arm and Sam68-YY. Structural comparisons revealed different modes of ligand recognition between the Arm domains of APC and other Arm-containing proteins.

  4. DEP domains: structurally similar but functionally different.

    PubMed

    Consonni, Sarah V; Maurice, Madelon M; Bos, Johannes L

    2014-05-01

    The Dishevelled, EGL-10 and pleckstrin (DEP) domain is a globular protein domain that is present in about ten human protein families with well-defined structural features. A picture is emerging that DEP domains mainly function in the spatial and temporal control of diverse signal transduction events by recruiting proteins to the plasma membrane. DEP domains can interact with various partners at the membrane, including phospholipids and membrane receptors, and their binding is subject to regulation.

  5. 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.

  6. The code and beyond: transcription regulation by the RNA polymerase II carboxy-terminal domain.

    PubMed

    Harlen, Kevin M; Churchman, L Stirling

    2017-04-01

    The carboxy-terminal domain (CTD) extends from the largest subunit of RNA polymerase II (Pol II) as a long, repetitive and largely unstructured polypeptide chain. Throughout the transcription process, the CTD is dynamically modified by post-translational modifications, many of which facilitate or hinder the recruitment of key regulatory factors of Pol II that collectively constitute the 'CTD code'. Recent studies have revealed how the physicochemical properties of the CTD promote phase separation in the presence of other low-complexity domains. Here, we discuss the intricacies of the CTD code and how the newly characterized physicochemical properties of the CTD expand the function of the CTD beyond the code.

  7. Neutralisation of specific surface carboxylates speeds up translocation of botulinum neurotoxin type B enzymatic domain.

    PubMed

    Pirazzini, Marco; Henke, Tina; Rossetto, Ornella; Mahrhold, Stefan; Krez, Nadja; Rummel, Andreas; Montecucco, Cesare; Binz, Thomas

    2013-11-29

    Botulinum neurotoxins translocate their enzymatic domain across vesicular membranes. The molecular triggers of this process are unknown. Here, we tested the possibility that this is elicited by protonation of conserved surface carboxylates. Glutamate-48, glutamate-653 and aspartate-877 were identified as possible candidates and changed into amide. This triple mutant showed increased neurotoxicity due to faster cytosolic delivery of the enzymatic domain; membrane translocation could take place at less acidic pH. Thus, neutralisation of specific negative surface charges facilitates membrane contact permitting a faster initiation of the toxin membrane insertion.

  8. Trait divergence and indirect interactions allow facilitation of congeneric species

    PubMed Central

    Beltrán, Elisa; Valiente-Banuet, Alfonso; Verdú, Miguel

    2012-01-01

    Background Plant facilitation occurs when the presence of a plant (i.e. a nurse plant) modifies the environment, making it more favourable for the establishment and survival of other species (i.e. facilitated plants), which can germinate and grow nearby. Facilitative associations can be maintained or turned into competition as the facilitated seedling grows. According to the competition-relatedness hypothesis that suggests that closely related species tend to compete more, facilitation turns into competition between phylogenetically close species. However, some examples of facilitation between congeneric species, which are supposed to be closely related species, have been found in nature. Scope In this work, some examples of congeneric facilitation and subsequent coexistence are reviewed and an attempt is made to explain those exceptions to the competition-relatedness hypothesis. Conclusions Two mechanisms are proposed that can switch the facilitation–competition balance: trait divergence and indirect interactions. When traits have diverged within the genus, the niche overlap is reduced and competition relaxed, thus allowing the coexistence of congeneric species. The presence of third interplayers (mycorrhizal fungi, seed dispersers, pollinators or pathogens) participating in the interaction between plants can alleviate the competition or enhance the reproduction and allow the coexistence of species that could not coexist in their absence. PMID:22543178

  9. 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.

  10. Cobalt intercalation at the graphene/iridium(111) interface: Influence of rotational domains, wrinkles, and atomic steps

    SciTech Connect

    Vlaic, S.; Kimouche, A.; Coraux, J.; Rougemaille, N.; Santos, B.; Locatelli, A.

    2014-03-10

    Using low-energy electron microscopy, we study Co intercalation under graphene grown on Ir(111). Depending on the rotational domain of graphene on which it is deposited, Co is found intercalated at different locations. While intercalated Co is observed preferentially at the substrate step edges below certain rotational domains, it is mostly found close to wrinkles below other domains. These results indicate that curved regions (near substrate atomic steps and wrinkles) of the graphene sheet facilitate Co intercalation and suggest that the strength of the graphene/Ir interaction determines which pathway is energetically more favorable.

  11. The influence of domain size on the response characteristics of a hurricane storm surge model

    NASA Astrophysics Data System (ADS)

    Blain, C. A.; Westerink, J. J.; Luettich, R. A.

    1994-09-01

    The influence of domain size on boundary condition specification and on computed storm surge response is investigated. Storm surge response along the Florida shelf in the Gulf of Mexico due to Hurricane Kate is examined over three domains using two different open ocean boundary forcing functions, a still water (or zero elevation) condition and an inverted barometer condition which accounts for the atmospheric pressure component of the meteorological forcing. The first domain is relatively small and is situated primarily on the continental shelf in the region of intense storm surge generation. A second domain includes the entire Gulf of Mexico basin. The final domain covers the Gulf of Mexico, contiguous basins, and extends out into the deep Atlantic Ocean. The computed storm surge response indicates that the small domain is inadequate, since cross-shelf boundaries are in regions of significant storm surge generation where surge and therefore boundary conditions are not known a priori. Also, the behavior of resonant modes that are physically excited within the Gulf of Mexico due to the passage of the hurricane is unknown at the boundaries of this small domain. The domain that includes the entire Gulf of Mexico captures the primary storm surge well but may not correctly model resonant modes. In general, these resonant modes are difficult to accurately set up by boundary condition specification, since they may be dependent on interactions between the Gulf and contiguous basins. The primary storm surge response as well as resonant modes excited by the storm are best represented using a domain which encompasses the western North Atlantic Ocean, the Caribbean Sea, and the Gulf of Mexico. This domain with deep Atlantic Ocean boundaries facilitates simple boundary condition specification and minimizes the influence of boundary conditions on storm surge generation in coastal regions. Basin resonant modes and basin to basin interactions are also captured.

  12. 22 CFR 120.11 - Public domain.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Public domain. 120.11 Section 120.11 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL TRAFFIC IN ARMS REGULATIONS PURPOSE AND DEFINITIONS § 120.11 Public domain. (a) Public domain means information which is published and which is generally...

  13. 22 CFR 120.11 - Public domain.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Public domain. 120.11 Section 120.11 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL TRAFFIC IN ARMS REGULATIONS PURPOSE AND DEFINITIONS § 120.11 Public domain. (a) Public domain means information which is published and which is generally...

  14. 22 CFR 120.11 - Public domain.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Public domain. 120.11 Section 120.11 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL TRAFFIC IN ARMS REGULATIONS PURPOSE AND DEFINITIONS § 120.11 Public domain. (a) Public domain means information which is published and which is generally...

  15. 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...

  16. 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

  17. 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

  18. Walking droplets in confined domains

    NASA Astrophysics Data System (ADS)

    Sáenz, Pedro; Bush, John

    2016-11-01

    A millimetric liquid drop can walk spontaneously along the surface of a vibrating fluid bath, propelled by a resonant interaction with its own wave field. These walking droplets exhibit features previously thought to be exclusive to the microscopic quantum realm. We here explore experimentally the dynamics and statistics of this macroscopic wave-particle system in confined domains, or 'corrals'. Particular attention is given to characterizing the influence of the corral geometry on the emergent probability distributions. The relation to analogous quantum systems (specifically, quantum corrals, the quantum mirage and scarring in Bose-Einstein condensates) is discussed. NSF support via CMMI-1333242.

  19. Changes in nucleoporin domain topology in response to chemical effectors.

    PubMed

    Paulillo, Sara M; Powers, Maureen A; Ullman, Katharine S; Fahrenkrog, Birthe

    2006-10-13

    Nucleoporins represent the molecular building blocks of nuclear pore complexes (NPCs), which mediate facilitated macromolecular trafficking between the cytoplasm and nucleus of eukaryotic cells. Phenylalanine-glycine (FG) repeat motifs are found in about one-third of the nucleoporins, and they provide major binding or docking sites for soluble transport receptors. We have shown recently that localization of the FG-repeat domains of vertebrate nucleoporins Nup153 and Nup214 within the NPC is influenced by its transport state. To test whether chemical effectors, such as calcium and ATP, influence the localization of the FG-repeat domains of Nup153 and Nup214 within the NPC, we performed immuno-electron microscopy of Xenopus oocyte nuclei using domain-specific antibodies against Nup153 and Nup214, respectively. Ca2+ and ATP are known to induce conformational changes in the NPC architecture, especially at the cytoplasmic face, but also at the nuclear basket of the NPC. We have found concentrations of calcium in the micromolar range or 1 mM ATP in the surrounding buffer leaves the spatial distribution of the FG-repeat of Nup153 and Nup214 largely unchanged. In contrast, ATP depletion, calcium store depletion by EGTA or thapsigargin, and high concentrations of divalent cation (i.e. 2 mM Ca2+ and 2 mM Mg2+) constrain the distribution of the FG-repeats of Nup153 and Nup214. Our data suggest that the location of the FG-repeat domains of Nup153 and Nup214 is sensitive to chemical changes within the near-field environment of the NPC.

  20. Time domain backcalculation of pavement

    NASA Astrophysics Data System (ADS)

    Matsui, Kunihito; Nishizawa, Tatsuo; Kikuta, Yukio

    1998-03-01

    Falling weight deflectometor (FWD) has been frequently used to evaluate structural integrity of pavement. The device applies an impulsive force on the surface of pavement and measure surface deflections at several locations including the place of loading. Although the test is dynamic, the data is regarded as pseudo-static data. According to common practice, using the peak load and the corresponding peak deflections, layer moduli are estimated in a static domain such that the measured peak deflections coincide with the corresponding calculated deflections based on the assumption of the theory of linear elasticity. This paper presents a method to back calculate layer moduli in dynamic domain such that the histories of both measured and calculated responses corresponding to the impulsive force coincide. Pavement is modeled by an axisymmetric linear elastic system. FEM is utilized coupled with Ritz vector to reduce a matrix and thus to improve computational efficiency. The backcalculation algorithm used is the Gauss-Newton method coupled with a truncated singular value decomposition.

  1. 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

  2. Positive consequences of conflict on decision making: when a conflict mindset facilitates choice.

    PubMed

    Savary, Jennifer; Kleiman, Tali; Hassin, Ran R; Dhar, Ravi

    2015-02-01

    Much research has shown that conflict is aversive and leads to increased choice deferral. In contrast, we have proposed that conflict can be beneficial. Specifically, exposure to nonconscious goal conflict can activate a mindset (a set of cognitive procedures) that facilitates the systematic processing of information without triggering the associated costs, such as negative affect and stress. In a conflict mindset, people should be better able to make tradeoffs and resolve choice conflict. We tested this proposition in 4 experiments, and demonstrated that priming conflicting goals before a decision increases choice in domains unrelated to the primed conflict. We further demonstrated that increased choice occurs because people in a conflict mindset process choice information more systematically, and we rule out several alternative explanations for the results.

  3. crm-1 facilitates BMP signaling to control body size in Caenorhabditis elegans.

    PubMed

    Fung, Wong Yan; Fat, Ko Frankie Chi; Eng, Cheah Kathryn Song; Lau, Chow King

    2007-11-01

    We have identified in Caenorhabditis elegans a homologue of the vertebrate Crim1, crm-1, which encodes a putative transmembrane protein with multiple cysteine-rich (CR) domains known to have bone morphogenetic proteins (BMPs) binding activity. Using the body morphology of C. elegans as an indicator, we showed that attenuation of crm-1 activity leads to a small body phenotype reminiscent of that of BMP pathway mutants. We showed that the crm-1 loss-of-function phenotype can be rescued by constitutive supply of sma-4 activity. crm-1 can enhance BMP signaling and this activity is dependent on the presence of the DBL-1 ligand and its receptors. crm-1 is expressed in neurons at the ventral nerve cord, where the DBL-1 ligand is produced. However, ectopic expression experiments reveal that crm-1 gene products act outside the DBL-1 producing cells and function non-autonomously to facilitate dbl/sma pathway signaling to control body size.

  4. 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.

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

    DOEpatents

    Freimuth, Paul I.

    2010-04-06

    The invention provides recombinant human CAR (coxsackievirus and adenovirus receptor) polypeptides which bind adenovirus. Specifically, polypeptides corresponding to adenovirus binding domain D1 and the entire extracellular domain of human CAR protein comprising D1 and D2 are provided. In another aspect, the invention provides nucleic acid sequences encoding these domains and expression vectors for producing the domains and bacterial cells containing such vectors. The invention also includes an isolated fusion protein comprised of the D1 polypeptide fused to a polypeptide which facilitates folding of D1 when expressed in bacteria. The functional D1 domain finds application in a therapeutic method for treating a patient infected with a CAR D1-binding virus, and also in a method for identifying an antiviral compound which interferes with viral attachment. The invention also provides a method for specifically targeting a cell for infection by a virus which binds to D1.

  6. Inflatable bladder to facilitate handling of heavy objects - A concept

    NASA Technical Reports Server (NTRS)

    Mc Goldrick, G. J.

    1969-01-01

    Inflatable bladder facilitates the removal of heavy, highly finished metal parts from tote boxes or shipping containers. The proposed concept permits removal without danger of damage to the parts or injury to handling personnel.

  7. Encountering Carl Rogers: His Views on Facilitating Groups.

    ERIC Educational Resources Information Center

    Landreth, Garry L.

    1984-01-01

    Presents Carl Rogers' views on facilitating groups, as expressed in a telephone dialogue seminar with graduate students in counselor education at North Texas State University. Discusses extended group marathons, cocounseling, nonverbal group exercises and the future of group work. (JAC)

  8. Dynamic facilitation picture of a higher-order glass singularity.

    PubMed

    Sellitto, Mauro; De Martino, Daniele; Caccioli, Fabio; Arenzon, Jeferson J

    2010-12-31

    We show that facilitated spin mixtures with a tunable facilitation reproduce, on a Bethe lattice, the simplest higher-order singularity scenario predicted by the mode-coupling theory (MCT) of liquid-glass transition. Depending on the facilitation strength, they yield either a discontinuous glass transition or a continuous one, with no underlying thermodynamic singularity. Similar results are obtained for facilitated spin models on a diluted Bethe lattice. The mechanism of dynamical arrest in these systems can be interpreted in terms of bootstrap and standard percolation and corresponds to a crossover from a compact to a fractal structure of the incipient spanning cluster of frozen spins. Theoretical and numerical simulation results are fully consistent with MCT predictions.

  9. The Overlooked Role of Facilitation in Biodiversity Experiments.

    PubMed

    Wright, Alexandra J; Wardle, David A; Callaway, Ragan; Gaxiola, Aurora

    2017-03-08

    Past research has demonstrated that decreased biodiversity often reduces ecosystem productivity, but variation in the shape of biodiversity-ecosystem function (BEF) relationships begets the need for a deeper mechanistic understanding of what drives these patterns. While mechanisms involving competition are often invoked, the role of facilitation is overlooked, or lumped within several less explicitly defined processes (e.g., complementarity effects). Here, we explore recent advances in understanding how facilitation affects BEF relationships and identify three categories of facilitative mechanisms that can drive variation in those relationships. Species interactions underlying BEF relationships are complex, but the framework we present provides a step toward understanding this complexity and predicting how facilitation contributes to the ecosystem role of biodiversity in a rapidly changing environment.

  10. Biohydrogen facilitated denitrification at biocathode in bioelectrochemical system (BES).

    PubMed

    Liu, Hao; Yan, Qun; Shen, Wei

    2014-11-01

    Reductive removal of nitrate in bioelectrochemical system (BES) at abiotic cathode, biocathode and biohydrogen facilitated biocathode were investigated. It was found that nitrate removal efficiency reached 95% and 59% at the biohydrogen facilitated biocathode and biocathode respectively, while which was only 13% at the abiotic cathode. Meanwhile, activity of nitrate reductase reached 0.701 g-N/Lh for the biohydrogen facilitated group, which was about 9.3 times of the biocathode group. Moreover, electrochemical performances as power density, ohmic resistance, and polarization resistance of the biohydrogen facilitated group reached 76.96 mW/m(3), 8.63 ohm and 383 ohm, respectively, which were better than two other groups. Finally, an obvious shift of bacterial community responsible for the enhanced nitrate reduction between the two biocathode groups was observed. Therefore, nitrate reduction in BES could be enhanced at the biocathode than that of the abiotic cathode, and then be further boosted with the combination of biohydrogen.

  11. The Role of the Facilitator in Couple Relationship Education.

    PubMed

    Ketring, Scott A; Bradford, Angela B; Davis, Stephanie Y; Adler-Baeder, Francesca; McGill, Julianne; Smith, Thomas A

    2017-03-11

    While much of the Couple Relationship Education (CRE) research has focused on participant factors, unexpectedly little research has considered how characteristics of those providing the programming shape its efficacy. The current study draws upon a diverse sample of 225 couples who received CRE from community educators to examine how facilitation alliance is related to relationship outcomes for men and women and whether having a facilitator with similar demographic characteristics is related to the alliance. Results suggest that the facilitation alliance is related to some-though not all-postprogram outcomes and these effects were uniform across gender and relationship status (married vs. unmarried). Having a facilitator of the same gender was associated with a stronger alliance. Implications are discussed.

  12. Facilitating Vocational Development Among Disadvantaged Inner-City Adolescents

    ERIC Educational Resources Information Center

    Hamdani, Asma

    1977-01-01

    The purpose of this study was to investigate whether the vocational development process of tenth-grade disadvantaged students can be facilitated through deliberate intervention in the form of supplementary learning experiences. (Author)

  13. Premovement facilitation of corticospinal excitability in patients with Parkinson's disease.

    PubMed

    Hiraoka, Koichi; Notani, Masaru; Iwata, Akira; Minamida, Fumiko; Abe, Kazuo

    2010-02-01

    The purpose of this study was to investigate the abnormality of premovement facilitation in patients with Parkinson's disease. Seven patients with Parkinson's disease and seven healthy subjects participated in this study. The subjects attempted abduction of the index finger in response to a visual start cue, and motor-evoked potentials were recorded from the first dorsal interosseous muscle before movement onset. The rate of premovement facilitation in patients with Parkinson's disease was slower than that in healthy subjects. Additionally, the rate of premovement facilitation as a function of delay from the start cue was positively correlated with the reaction time. These findings indicate that premovement facilitation is abnormal in patients with Parkinson's disease. This abnormality may be partially related to akinesia.

  14. Reciprocal feeding facilitation between above- and below-ground herbivores.

    PubMed

    McKenzie, Scott W; Vanbergen, Adam J; Hails, Rosemary S; Jones, T Hefin; Johnson, Scott N

    2013-10-23

    Interspecific interactions between insect herbivores predominantly involve asymmetric competition. By contrast, facilitation, whereby herbivory by one insect benefits another via induced plant susceptibility, is uncommon. Positive reciprocal interactions between insect herbivores are even rarer. Here, we reveal a novel case of reciprocal feeding facilitation between above-ground aphids (Amphorophora idaei) and root-feeding vine weevil larvae (Otiorhynchus sulcatus), attacking red raspberry (Rubus idaeus). Using two raspberry cultivars with varying resistance to these herbivores, we further demonstrate that feeding facilitation occurred regardless of host plant resistance. This positive reciprocal interaction operates via an, as yet, unreported mechanism. Specifically, the aphid induces compensatory growth, possibly as a prelude to greater resistance/tolerance, whereas the root herbivore causes the plant to abandon this strategy. Both herbivores may ultimately benefit from this facilitative interaction.

  15. The Motivation-Facilitation Theory of Prenatal Care Access.

    PubMed

    Phillippi, Julia C; Roman, Marian W

    2013-01-01

    Despite the availability of services, accessing health care remains a problem in the United States and other developed countries. Prenatal care has the potential to improve perinatal outcomes and decrease health disparities, yet many women struggle with access to care. Current theories addressing access to prenatal care focus on barriers, although such knowledge is minimally useful for clinicians. We propose a middle-range theory, the motivation-facilitation theory of prenatal care access, which condenses the prenatal care access process into 2 interacting components: motivation and facilitation. Maternal motivation is the mother's desire to begin and maintain care. Facilitation represents the goal of the clinic to create easy, open access to person-centered beneficial care. This simple model directs the focus of research and change to the interface of the woman and the clinic and encourages practice-level interventions that facilitate women entering and maintaining prenatal care.

  16. Online Chemistry Modules: Interaction and Effective Faculty Facilitation

    ERIC Educational Resources Information Center

    Slocum, Laura E.; Towns Marcy Hamby; Zielinski, Theresa Julia

    2004-01-01

    Computer supported collaborative learning, cooperative learning combined with electronic communication, physical chemistry online modules, use of discussion boards, its advantages and limitations are experimented and discussed. The most important finding is the example of effective online faculty facilitation and interaction.

  17. Immunogenicity of the outer domain of a HIV-1 clade C gp120

    PubMed Central

    Chen, Hongying; Xu, Xiaodong; Jones, Ian M

    2007-01-01

    Background The possibility that a sub domain of a C clade HIV-1 gp120 could act as an effective immunogen was investigated. To do this, the outer domain (OD) of gp120CN54 was expressed and characterized in a construct marked by a re-introduced conformational epitope for MAb 2G12. The expressed sequence showed efficient epitope retention on the isolated ODCN54 suggesting authentic folding. To facilitate purification and subsequent immunogenicity ODCN54 was fused to the Fc domain of human IgG1. Mice were immunised with the resulting fusion proteins and also with gp120CN54-Fc and gp120 alone. Results Fusion to Fc was found to stimulate antibody titre and Fc tagged ODCN54 was substantially more immunogenic than non-tagged gp120. Immunogenicity appeared the result of Fc facilitated antigen processing as immunisation with an Fc domain mutant that reduced binding to the FcR lead to a reduction in antibody titre when compared to the parental sequence. The breadth of the antibody response was assessed by serum reaction with five overlapping fragments of gp120CN54 expressed as GST fusion proteins in bacteria. A predominant anti-inner domain and anti-V3C3 response was observed following immunisation with gp120CN54-Fc and an anti-V3C3 response to the ODCN54-Fc fusion. Conclusion The outer domain of gp120CN54 is correctly folded following expression as a C terminal fusion protein. Immunogenicity is substantial when targeted to antigen presenting cells but shows V3 dominance in the polyvalent response. The gp120 outer domain has potential as a candidate vaccine component. PMID:17509143

  18. Defining E-Services Using a Co-Design Platform: Example in the Domain of Instrumental E-Learning

    ERIC Educational Resources Information Center

    Sebastien, Olivier; Conruyt, Noel; Grosser, David

    2008-01-01

    Purpose: One of the aims of expert knowledge management via information and communication technology is to improve the efficiency of knowledge transfer to non-specialists, and to facilitate the implementation of service-products that are adapted so as to be truly used. The aim of this paper is to describe an example in the domain of instrumental…

  19. 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.

  20. Role of "external facilitation" in implementation of research findings: a qualitative evaluation of facilitation experiences in the Veterans Health Administration

    PubMed Central

    Stetler, Cheryl B; Legro, Marcia W; Rycroft-Malone, Joanne; Bowman, Candice; Curran, Geoffrey; Guihan, Marylou; Hagedorn, Hildi; Pineros, Sandra; Wallace, Carolyn M

    2006-01-01

    Background Facilitation has been identified in the literature as a potentially key component of successful implementation. It has not, however, either been well-defined or well-studied. Significant questions remain about the operational definition of facilitation and about the relationship of facilitation to other interventions, especially to other change agent roles when used in multi-faceted implementation projects. Researchers who are part of the Quality Enhancement Research Initiative (QUERI) are actively exploring various approaches and processes, including facilitation, to enable implementation of best practices in the Veterans Health Administration health care system – the largest integrated healthcare system in the United States. This paper describes a systematic, retrospective evaluation of implementation-related facilitation experiences within QUERI, a quality improvement program developed by the US Department of Veterans Affairs. Methods A post-hoc evaluation was conducted through a series of semi-structured interviews to examine the concept of facilitation across several multi-site QUERI implementation studies. The interview process is based on a technique developed in the field of education, which systematically enhances learning through experience by stimulating recall and reflection regarding past complex activities. An iterative content analysis approach relative to a set of conceptually-based interview questions was used for data analysis. Findings Findings suggest that facilitation, within an implementation study initiated by a central change agency, is a deliberate and valued process of interactive problem solving and support that occurs in the context of a recognized need for improvement and a supportive interpersonal relationship. Facilitation was described primarily as a distinct role with a number of potentially crucial behaviors and activities. Data further suggest that external facilitators were likely to use or integrate other

  1. Colloid-Facilitated Transport of Radionuclides through the Vadose Zone

    SciTech Connect

    Flury, Markus; Harsh, James B.; Zachara, John M.; McCarthy, John F.; Lichtner, Peter C.

    2006-05-31

    This project seeks to improve the basic understanding of the role of colloids in facilitating the transport of contaminants in the vadose zone. We focus on three major thrusts: (1) thermodynamic stability and mobility of colloids formed by reactions of sediments with highly alkaline tank waste solutions, (2) colloid-contaminant interactions, and (3) in-situ colloid mobilization and colloid facilitated contaminant transport occurring in both contaminated and uncontaminated Hanford sediments.

  2. The Use of Benzodiazepines to Facilitate Sexual Assault.

    PubMed

    Montgomery, M A

    2010-01-01

    Benzodiazepines are one of the classes of drugs most commonly associated with drug-facilitated sexual assault. As a widely prescribed class of medications and abused drugs, benzodiazepines are extensively available. Their sedating and amnesic effects make them effective candidates for use in drug-facilitated assaults. Detection methods for benzodiazepines and their metabolites in biological fluids are plentiful, but methods must be tailored to the low concentrations of drugs and metabolites expected to be encountered in these cases.

  3. Frequency domain, waveform inversion of laboratory crosswell radar data

    USGS Publications Warehouse

    Ellefsen, Karl J.; Mazzella, Aldo T.; Horton, Robert J.; McKenna, Jason R.

    2010-01-01

    A new waveform inversion for crosswell radar is formulated in the frequency-domain for a 2.5D model. The inversion simulates radar waves using the vector Helmholtz equation for electromagnetic waves. The objective function is minimized using a backpropagation method suitable for a 2.5D model. The inversion is tested by processing crosswell radar data collected in a laboratory tank. The estimated model is consistent with the known electromagnetic properties of the tank. The formulation for the 2.5D model can be extended to inversions of acoustic and elastic data.

  4. Collective magnetism at multiferroic vortex domain walls.

    PubMed

    Geng, Yanan; Lee, N; Choi, Y J; Cheong, S-W; Wu, Weida

    2012-12-12

    Cross-coupled phenomena of multiferroic domains and domain walls are of fundamental scientific and technological interest. Using cryogenic magnetic force microscopy, we find alternating net magnetic moments at ferroelectric domain walls around vortex cores in multiferroic hexagonal ErMnO(3), which correlate with each other throughout the entire vortex network. This collective nature of domain wall magnetism originates from the uncompensated Er(3+) moments at domain walls and the self-organization of the vortex network. Our results demonstrate that the collective domain wall magnetism can be controlled by external magnetic fields and represent a major advancement in the manipulation of local magnetic moments by harnessing cross-coupled domain walls.

  5. [Mechanisms of neurotransmitter release facilitation in strontium solutions].

    PubMed

    Mukhamed'iarov, M A; Kochunova, Iu O; Telina, E N; Zefirov, A L

    2008-02-01

    Mechanisms of neurotransmitter release facilitation were studied using electrophysiological recording of end-plate currents (EPC) and nerve ending (NE) responses after substitution of extracellular Ca ions with Sr ions at the frog neuromuscular junction. The solutions with 0.5 mM concentration of Ca ions (calcium solution) or 1 mM concentration of Sr ions (strontium solution) were used where baseline neurotransmitter release (at low-frequency stimulation) is equal. Decay of paired-pulse facilitation of EPC at calcium solutions with increase of interpulse interval from 5 to 500 ms was well described by three-exponential function consisting of early, first and second components. Facilitation at strontium solutions was significantly diminished due mainly to decrease of early and first components. At the same time, EPC facilitation with rhythmic stimulation (10 or 50 imp/s) at strontium solutions was significantly increased. Also more pronounced decrease of NE response 3rd phase, reflecting potassium currents was detected under rhythmic stimulation of 50 imp/s at strontium solutions comparing to calcium solutions. It was concluded that facilitation sites underlying first and early components had lower affinity to Sr ions than to Ca ions. The enhancement of frequency facilitation at strontium solutions is mediated by two mechanisms: more pronounced broadening of NE action potential and increase of bivalent cation influx due to feebly marked activation of Ca(2+)-dependent potassium current by Sr ions, and slower dynamics of Sr(2+) removal from NE axoplasm comparing to Ca(2+).

  6. Key symptom domains to be assessed in fibromyalgia (outcome measures in rheumatoid arthritis clinical trials).

    PubMed

    Choy, Ernest H; Mease, Philip J

    2009-05-01

    This article discusses the key symptom domains to be assessed in fibromyalgia. Development of a consensus on a core set of outcome measures that should be assessed and reported in all clinical trials is needed to facilitate interpretation, pooling, and comparison of results. This aligns with the key objective of the Outcome Measures in Rheumatoid Arthritis Clinical Trials initiative to improve outcome measurement in rheumatic diseases through a data-driven interactive consensus process.

  7. Barriers and Facilitators to Exercise Participation in People with Hip and/or Knee Osteoarthritis: Synthesis of the Literature Using Behavior Change Theory.

    PubMed

    Dobson, Fiona; Bennell, Kim L; French, Simon D; Nicolson, Philippa J A; Klaasman, Remco N; Holden, Melanie A; Atkins, Lou; Hinman, Rana S

    2016-05-01

    Exercise is recommended for hip and knee osteoarthritis (OA). Patient initiation of, and adherence to, exercise is key to the success of managing symptoms. This study aimed to (1) identify modifiable barriers and facilitators to participation in intentional exercise in hip and/or knee OA, and (2) synthesize findings using behavior change theory. A scoping review with systematic searches was conducted through March 2015. Two reviewers screened studies for eligibility. Barriers and facilitators were extracted and synthesized according to the Theoretical Domains Framework (TDF) by two independent reviewers. Twenty-three studies (total of 4633 participants) were included. The greatest number of unique barriers and facilitators mapped to the Environmental Context and Resources domain. Many barriers were related to Beliefs about Consequences and Beliefs about Capabilities, whereas many facilitators were related to Reinforcement. Clinicians should take a proactive role in facilitating exercise uptake and adherence, rather than trusting patients to independently overcome barriers to exercise. Strategies that may be useful include a personalized approach to exercise prescription, considering environmental context and available resources, personalized education about beneficial consequences of exercise and reassurance about exercise capability, and use of reinforcement strategies. Future research should investigate the effectiveness of behavior change interventions that specifically target these factors.

  8. Structure and function of KH domains.

    PubMed

    Valverde, Roberto; Edwards, Laura; Regan, Lynne

    2008-06-01

    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.

  9. 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.

  10. Distinct self-interaction domains promote Multi Sex Combs accumulation in and formation of the Drosophila histone locus body.

    PubMed

    Terzo, Esteban A; Lyons, Shawn M; Poulton, John S; Temple, Brenda R S; Marzluff, William F; Duronio, Robert J

    2015-04-15

    Nuclear bodies (NBs) are structures that concentrate proteins, RNAs, and ribonucleoproteins that perform functions essential to gene expression. How NBs assemble is not well understood. We studied the Drosophila histone locus body (HLB), a NB that concentrates factors required for histone mRNA biosynthesis at the replication-dependent histone gene locus. We coupled biochemical analysis with confocal imaging of both fixed and live tissues to demonstrate that the Drosophila Multi Sex Combs (Mxc) protein contains multiple domains necessary for HLB assembly. An important feature of this assembly process is the self-interaction of Mxc via two conserved N-terminal domains: a LisH domain and a novel self-interaction facilitator (SIF) domain immediately downstream of the LisH domain. Molecular modeling suggests that the LisH and SIF domains directly interact, and mutation of either the LisH or the SIF domain severely impairs Mxc function in vivo, resulting in reduced histone mRNA accumulation. A region of Mxc between amino acids 721 and 1481 is also necessary for HLB assembly independent of the LisH and SIF domains. Finally, the C-terminal 195 amino acids of Mxc are required for recruiting FLASH, an essential histone mRNA-processing factor, to the HLB. We conclude that multiple domains of the Mxc protein promote HLB assembly in order to concentrate factors required for histone mRNA biosynthesis.

  11. Brap2 facilitates HsCdc14A Lys-63 linked ubiquitin modification.

    PubMed

    Chen, Jing-Sen; Hu, Hai-Ying; Zhang, Shuo; He, Min; Hu, Ren-Ming

    2009-05-01

    Protein phosphotase Cdc14 (Cell division cycle gene 14) is a key regulator of late mitotic events in Saccharomyces cerevisiae. However the function of human Cdc14 (HsCdc14A & B) and its regulatory network are still elusive. In this study, we identified a new partner of HsCdc14A named Brap2 (BRCA1 associated protein 2) using yeast two-hybrid screening assay. The interaction between these two proteins is confirmed by co-immunoprecipitation in human HEK 293T cells. Brap2 co-localizes with HsCdc14A on mitotic spindle poles and over-expression of Brap2 causes multiple spindle poles. Furthermore, we found that Brap2, which has intrinsic RING domain dependent E3 ligase activity, facilitates HsCdc14A Lys-63 linked ubiquitin modification, indicating that Brap2 may be the ubiquitin E3 Ligase of HsCdc14A. Our findings imply that Brap2 plays a significant role in cell cycle regulation besides its facilitation of HsCdc14A ubiquitination.

  12. Latent memory facilitates relearning through molecular signaling mechanisms that are distinct from original learning.

    PubMed

    Menges, Steven A; Riepe, Joshua R; Philips, Gary T

    2015-09-01

    A highly conserved feature of memory is that it can exist in a latent, non-expressed state which is revealed during subsequent learning by its ability to significantly facilitate (savings) or inhibit (latent inhibition) subsequent memory formation. Despite the ubiquitous nature of latent memory, the mechanistic nature of the latent memory trace and its ability to influence subsequent learning remains unclear. The model organism Aplysia californica provides the unique opportunity to make strong links between behavior and underlying cellular and molecular mechanisms. Using Aplysia, we have studied the mechanisms of savings due to latent memory for a prior, forgotten experience. We previously reported savings in the induction of three distinct temporal domains of memory: short-term (10min), intermediate-term (2h) and long-term (24h). Here we report that savings memory formation utilizes molecular signaling pathways that are distinct from original learning: whereas the induction of both original intermediate- and long-term memory in naïve animals requires mitogen activated protein kinase (MAPK) activation and ongoing protein synthesis, 2h savings memory is not disrupted by inhibitors of MAPK or protein synthesis, and 24h savings memory is not dependent on MAPK activation. Collectively, these findings reveal that during forgetting, latent memory for the original experience can facilitate relearning through molecular signaling mechanisms that are distinct from original learning.

  13. Functional domains in tetraspanin proteins.

    PubMed

    Stipp, Christopher S; Kolesnikova, Tatiana V; Hemler, Martin E

    2003-02-01

    Exciting new findings have emerged about the structure, function and biochemistry of tetraspanin proteins. Five distinct tetraspanin regions have now been delineated linking structural features to specific functions. Within the large extracellular loop of tetraspanins, there is a variable region that mediates specific interactions with other proteins, as well as a more highly conserved region that has been suggested to mediate homodimerization. Within the transmembrane region, the four tetraspanin transmembrane domains are probable sites of both intra- and inter-molecular interactions that are crucial during biosynthesis and assembly of the network of tetraspanin-linked membrane proteins known as the 'tetraspanin web'. In the intracellular juxtamembrane region, palmitoylation of cysteine residues also contributes to tetraspanin web assembly, and the C-terminal cytoplasmic tail region could provide specific functional links to cytoskeletal or signaling proteins.

  14. Tetramer formation in Arabidopsis MADS domain proteins: analysis of a protein-protein interaction network

    PubMed Central

    2014-01-01

    Background MADS domain proteins are transcription factors that coordinate several important developmental processes in plants. These proteins interact with other MADS domain proteins to form dimers, and it has been proposed that they are able to associate as tetrameric complexes that regulate transcription of target genes. Whether the formation of functional tetramers is a widespread property of plant MADS domain proteins, or it is specific to few of these transcriptional regulators remains unclear. Results We analyzed the structure of the network of physical interactions among MADS domain proteins in Arabidopsis thaliana. We determined the abundance of subgraphs that represent the connection pattern expected for a MADS domain protein heterotetramer. These subgraphs were significantly more abundant in the MADS domain protein interaction network than in randomized analogous networks. Importantly, these subgraphs are not significantly frequent in a protein interaction network of TCP plant transcription factors, when compared to expectation by chance. In addition, we found that MADS domain proteins in tetramer-like subgraphs are more likely to be expressed jointly than proteins in other subgraphs. This effect is mainly due to proteins in the monophyletic MIKC clade, as there is no association between tetramer-like subgraphs and co-expression for proteins outside this clade. Conclusions Our results support that the tendency to form functional tetramers is widespread in the MADS domain protein-protein interaction network. Our observations also suggest that this trend is prevalent, or perhaps exclusive, for proteins in the MIKC clade. Because it is possible to retrodict several experimental results from our analyses, our work can be an important aid to make new predictions and facilitates experimental research on plant MADS domain proteins. PMID:24468197

  15. Discoidin domain receptor functions in physiological and pathological conditions

    PubMed Central

    Leitinger, Birgit

    2014-01-01

    The discoidin domain receptors, DDR1 and DDR2, are non-integrin collagen receptors that are members of the receptor tyrosine kinase family. Both DDRs bind a number of different collagen types and play important roles in embryo development. Dysregulated DDR function is associated with progression of various human diseases, including fibrosis, arthritis and cancer. By interacting with key components of the extracellular matrix and displaying distinct activation kinetics, the DDRs form a unique subfamily of receptor tyrosine kinases. DDR-facilitated cellular functions include cell migration, cell survival, proliferation and differentiation, as well as remodelling of extracellular matrices. This review summarises the current knowledge of DDR-ligand interactions, DDR-initiated signal pathways and the molecular mechanisms that regulate receptor function. Also discussed are the roles of DDRs in development and disease progression. PMID:24725424

  16. Charged domain walls under super-band-gap illumination

    NASA Astrophysics Data System (ADS)

    Sturman, B.; Podivilov, E.

    2017-03-01

    Charged domain walls (CDWs), which possess metallic-type conductivity and can be created and controlled in the bulk of wide-band-gap ferroelectrics, attract nowadays a strong research interest. The most advanced method for production of stable CDWs involves weak super-band-gap illumination. Here, we investigate theoretically the impact of this illumination on the major wall properties including the energy and the spatial profiles of the polarization, of the electrostatic potential, and of the compensating charge carriers. The key material parameters determining the effect of light are the zero-field polarization strength, the dielectric permittivity, and the trap concentration. The main predictions are substantial reduction of the wall energies and decrease of the electric wall potential under light. These features facilitate creation of dense CDWs patterns and accessibility of the metallic-type wall conductivity.

  17. Domain Adaptation with Conditional Transferable Components

    PubMed Central

    Gong, Mingming; Zhang, Kun; Liu, Tongliang; Tao, Dacheng; Glymour, Clark; Schölkopf, Bernhard

    2017-01-01

    Domain adaptation arises in supervised learning when the training (source domain) and test (target domain) data have different distributions. Let X and Y denote the features and target, respectively, previous work on domain adaptation mainly considers the covariate shift situation where the distribution of the features P(X) changes across domains while the conditional distribution P(Y∣X) stays the same. To reduce domain discrepancy, recent methods try to find invariant components T(X) that have similar P(T(X)) on different domains by explicitly minimizing a distribution discrepancy measure. However, it is not clear if P(Y∣T(X)) in different domains is also similar when P(Y∣X) changes. Furthermore, transferable components do not necessarily have to be invariant. If the change in some components is identifiable, we can make use of such components for prediction in the target domain. In this paper, we focus on the case where P(X∣Y) and P(Y) both change in a causal system in which Y is the cause for X. Under appropriate assumptions, we aim to extract conditional transferable components whose conditional distribution P(T(X)∣Y) is invariant after proper location-scale (LS) transformations, and identify how P(Y) changes between domains simultaneously. We provide theoretical analysis and empirical evaluation on both synthetic and real-world data to show the effectiveness of our method. PMID:28239433

  18. Domain Adaptation with Conditional Transferable Components.

    PubMed

    Gong, Mingming; Zhang, Kun; Liu, Tongliang; Tao, Dacheng; Glymour, Clark; Schölkopf, Bernhard

    2016-06-01

    Domain adaptation arises in supervised learning when the training (source domain) and test (target domain) data have different distributions. Let X and Y denote the features and target, respectively, previous work on domain adaptation mainly considers the covariate shift situation where the distribution of the features P(X) changes across domains while the conditional distribution P(Y∣X) stays the same. To reduce domain discrepancy, recent methods try to find invariant components [Formula: see text] that have similar [Formula: see text] on different domains by explicitly minimizing a distribution discrepancy measure. However, it is not clear if [Formula: see text] in different domains is also similar when P(Y∣X) changes. Furthermore, transferable components do not necessarily have to be invariant. If the change in some components is identifiable, we can make use of such components for prediction in the target domain. In this paper, we focus on the case where P(X∣Y) and P(Y) both change in a causal system in which Y is the cause for X. Under appropriate assumptions, we aim to extract conditional transferable components whose conditional distribution [Formula: see text] is invariant after proper location-scale (LS) transformations, and identify how P(Y) changes between domains simultaneously. We provide theoretical analysis and empirical evaluation on both synthetic and real-world data to show the effectiveness of our method.

  19. Amplification of TLO Mediator Subunit Genes Facilitate Filamentous Growth in Candida Spp.

    PubMed Central

    Liu, Zhongle; Moran, Gary P.; Myers, Lawrence C.

    2016-01-01

    Filamentous growth is a hallmark of C. albicans pathogenicity compared to less-virulent ascomycetes. A multitude of transcription factors regulate filamentous growth in response to specific environmental cues. Our work, however, suggests the evolutionary history of C. albicans that resulted in its filamentous growth plasticity may be tied to a change in the general transcription machinery rather than transcription factors and their specific targets. A key genomic difference between C. albicans and its less-virulent relatives, including its closest relative C. dubliniensis, is the unique expansion of the TLO (TeLOmere-associated) gene family in C. albicans. Individual Tlo proteins are fungal-specific subunits of Mediator, a large multi-subunit eukaryotic transcriptional co-activator complex. This amplification results in a large pool of ‘free,’ non-Mediator associated, Tlo protein present in C. albicans, but not in C. dubliniensis or other ascomycetes with attenuated virulence. We show that engineering a large ‘free’ pool of the C. dubliniensis Tlo2 (CdTlo2) protein in C. dubliniensis, through overexpression, results in a number of filamentation phenotypes typically associated only with C. albicans. The amplitude of these phenotypes is proportional to the amount of overexpressed CdTlo2 protein. Overexpression of other C. dubliniensis and C. albicans Tlo proteins do result in these phenotypes. Tlo proteins and their orthologs contain a Mediator interaction domain, and a potent transcriptional activation domain. Nuclear localization of the CdTlo2 activation domain, facilitated naturally by the Tlo Mediator binding domain or artificially through an appended nuclear localization signal, is sufficient for the CdTlo2 overexpression phenotypes. A C. albicans med3 null mutant causes multiple defects including the inability to localize Tlo proteins to the nucleus and reduced virulence in a murine systemic infection model. Our data supports a model in which the

  20. Facilitating classroom based interprofessional learning: a grounded theory study of university educators' perceptions of their role adequacy as facilitators.

    PubMed

    Derbyshire, Julie A; Machin, Alison I; Crozier, Suzanne

    2015-01-01

    The provision of inter professional learning (IPL) within undergraduate programmes is now well established within many Higher Education Institutions (HEIs). IPL aims to better equip nurses and other health professionals with effective collaborative working skills and knowledge to improve the quality of patient care. Although there is still ambiguity in relation to the optimum timing and method for delivering IPL, effective facilitation is seen as essential. This paper reports on a grounded theory study of university educators' perceptions of the knowledge and skills needed for their role adequacy as IPL facilitators. Data was collected using semi structured interviews with nine participants who were theoretically sampled from a range of professional backgrounds, with varied experiences of education and involvement in facilitating IPL. Constant comparative analysis was used to generate four data categories: creating and sustaining an IPL group culture through transformational IPL leadership (core category), readiness for IPL facilitation, drawing on past interprofessional learning and working experiences and role modelling an interprofessional approach. The grounded theory generated from this study, although propositional, suggests that role adequacy for IPL facilitation is dependent on facilitator engagement in a process of 'transformational interprofessional learning leadership' to create and sustain a group culture.