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Sample records for a2 domain facilitate

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

    PubMed Central

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

    2014-01-01

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

  2. Annexin A2 facilitates endocytic trafficking of antisense oligonucleotides

    PubMed Central

    Wang, Shiyu; Sun, Hong; Tanowitz, Michael; Liang, Xue-hai; Crooke, Stanley T.

    2016-01-01

    Chemically modified antisense oligonucleotides (ASOs) designed to mediate site-specific cleavage of RNA by RNase H1 are used as research tools and as therapeutics. ASOs modified with phosphorothioate (PS) linkages enter cells via endocytotic pathways. The mechanisms by which PS-ASOs are released from membrane-enclosed endocytotic organelles to reach target RNAs remain largely unknown. We recently found that annexin A2 (ANXA2) co-localizes with PS-ASOs in late endosomes (LEs) and enhances ASO activity. Here, we show that co-localization of ANXA2 with PS-ASO is not dependent on their direct interactions or mediated by ANXA2 partner protein S100A10. Instead, ANXA2 accompanies the transport of PS-ASOs to LEs, as ANXA2/PS-ASO co-localization was observed inside LEs. Although ANXA2 appears not to affect levels of PS-ASO internalization, ANXA2 reduction caused significant accumulation of ASOs in early endosomes (EEs) and reduced localization in LEs and decreased PS-ASO activity. Importantly, the kinetics of PS-ASO activity upon free uptake show that target mRNA reduction occurs at least 4 hrs after PS-ASOs exit from EEs and is coincident with release from LEs. Taken together, our results indicate that ANXA2 facilitates PS-ASO trafficking from early to late endosomes where it may also contribute to PS-ASO release. PMID:27378781

  3. Facilitating Inter-Domain Synergies in Ambient Assisted Living Environments.

    PubMed

    Schwartze, Jonas; Schrom, Harald; Wolf, Klaus-Hendrik; Marschollek, Michael

    2016-01-01

    Current Ambient Assisted Living (AAL) environments lack integration of sensors and actuators of other sub-domains. Creating technical and organizational integration is addressed by the BASIS project (Build Automation by a Scalable and Intelligent System), which aims to build a cross-domain home bus system. The main objective of this paper is to present an overview of design, architecture and state of realization of BASIS by describing the requirements development process, underlying hardware design and software architecture. We built a distributed system of one independent building manager with several redundantly meshed segment controllers, each controlling a bus segment with any number of bus nodes. The software system layer is divided into logical partitions representing each sub-domain. Structured data storage is possible with a special FHIR based home centered data warehouse. The system has been implemented in six apartments running under daily living conditions. BASIS integrates a broad range of sub-domains, which poses challenges to all project partners in terms of a common terminology, and project management methods, but enables development of inter-domain synergies like using the same sensor and actuator hardware for a broad range of services and use cases. PMID:27577428

  4. Facilitating Inter-Domain Synergies in Ambient Assisted Living Environments.

    PubMed

    Schwartze, Jonas; Schrom, Harald; Wolf, Klaus-Hendrik; Marschollek, Michael

    2016-01-01

    Current Ambient Assisted Living (AAL) environments lack integration of sensors and actuators of other sub-domains. Creating technical and organizational integration is addressed by the BASIS project (Build Automation by a Scalable and Intelligent System), which aims to build a cross-domain home bus system. The main objective of this paper is to present an overview of design, architecture and state of realization of BASIS by describing the requirements development process, underlying hardware design and software architecture. We built a distributed system of one independent building manager with several redundantly meshed segment controllers, each controlling a bus segment with any number of bus nodes. The software system layer is divided into logical partitions representing each sub-domain. Structured data storage is possible with a special FHIR based home centered data warehouse. The system has been implemented in six apartments running under daily living conditions. BASIS integrates a broad range of sub-domains, which poses challenges to all project partners in terms of a common terminology, and project management methods, but enables development of inter-domain synergies like using the same sensor and actuator hardware for a broad range of services and use cases.

  5. Eukaryotic RNAse H shares a conserved domain with caulimovirus proteins that facilitate translation of polycistronic RNA.

    PubMed Central

    Mushegian, A R; Edskes, H K; Koonin, E V

    1994-01-01

    RNAse H (RNH1 protein) from the trypanosomatid Crithidia fasciculata has a functionally uncharacterized N-terminal domain dispensable for the RNAse H activity. Using computer methods for database search and multiple alignment, we show that the N-terminal domains of RNH1 and its homologue encoded by a cDNA from chicken lens are related to the conserved domain in caulimovirus ORF VI product that facilitates translation of polycistronic virus RNA in plant cells. We hypothesize that the N-terminal domain of eukaryotic RNAse H performs an as yet uncharacterized regulatory function, possibly in mRNA translation or turnover. PMID:7937142

  6. Substrate recognition by gelatinase A: the C-terminal domain facilitates surface diffusion.

    PubMed Central

    Collier, I E; Saffarian, S; Marmer, B L; Elson, E L; Goldberg, G

    2001-01-01

    An investigation of gelatinase A binding to gelatin produced results that are inconsistent with a traditional bimolecular Michaelis-Menten formalism but are effectively accounted for by a power law characteristic of fractal kinetics. The main reason for this inconsistency is that the bulk of the gelatinase A binding depends on its ability to diffuse laterally on the gelatin surface. Most interestingly, we show that the anomalous lateral diffusion and, consequently, the binding to gelatin is greatly facilitated by the C-terminal hemopexin-like domain of the enzyme whereas the specificity of binding resides with the fibronectin-like gelatin-binding domain. PMID:11566806

  7. 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

  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. Acidic domain in dentin phosphophoryn facilitates cellular uptake: implications in targeted protein delivery.

    PubMed

    Ravindran, Sriram; Snee, Preston T; Ramachandran, Amsaveni; George, Anne

    2013-05-31

    Dentin phosphophoryn is nature's most acidic protein found predominantly in the dentin extracellular matrix. Its unique amino acid composition containing Asp-Ser (DS)-rich repeats makes it highly anionic. It has a low isoelectric point (pI 1.1) and, therefore, tends to be negatively charged at physiological pH. Phosphophoryn is normally associated with matrix mineralization as it can bind avidly to Ca(2+). It is well known that several macromolecules present in the extracellular matrix can be internalized and localized to specific intracellular compartments. In this study we demonstrate that dentin phosphophoryn (DPP) is internalized by several cell types via a non-conventional endocytic process. Utilizing a DSS polypeptide derived from DPP, we demonstrate the repetitive DSS-rich domain facilitates that endocytosis. As a proof-of-concept, we further demonstrate the use of this polypeptide as a protein delivery vehicle by delivering the osteoblast transcription factor Runx2 to the nucleus of mesenchymal cells. The functionality of the endocytosed Runx2 protein was demonstrated by performing gene expression analysis of Runx2 target genes. Nuclear localization was also demonstrated with the fusion protein DSS-Runx2 conjugated to quantum dots in two- and three-dimensional culture models in vitro and in vivo. Overall, we demonstrate that the DSS domain of DPP functions as a novel cell-penetrating peptide, and these findings demonstrate new opportunities for intracellular delivery of therapeutic proteins and cell tracking in vivo.

  10. 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…

  11. The Ubiquitin-associated Domain of Cellular Inhibitor of Apoptosis Proteins Facilitates Ubiquitylation*

    PubMed Central

    Budhidarmo, Rhesa; Day, Catherine L.

    2014-01-01

    The cellular inhibitor of apoptosis (cIAP) proteins are essential RING E3 ubiquitin ligases that regulate apoptosis and inflammatory responses. cIAPs contain a ubiquitin-associated (UBA) domain that binds ubiquitin and is implicated in the regulation of cell survival and proteasomal degradation. Here we show that mutation of the MGF and LL motifs in the UBA domain of cIAP1 caused unfolding and increased cIAP1 multimonoubiquitylation. By developing a UBA mutant that disrupted ubiquitin binding but not the structure of the UBA domain, we found that the UBA domain enhances cIAP1 and cIAP2 ubiquitylation. We demonstrate that the UBA domain binds to the UbcH5b∼Ub conjugate, and this promotes RING domain-dependent monoubiquitylation. This study establishes ubiquitin-binding modules, such as the UBA domain, as important regulatory modules that can fine tune the activity of E3 ligases. PMID:25065467

  12. The Habc Domain of the SNARE Vam3 Interacts with the HOPS Tethering Complex to Facilitate Vacuole Fusion*

    PubMed Central

    Lürick, Anna; Kuhlee, Anne; Bröcker, Cornelia; Kümmel, Daniel; Raunser, Stefan; Ungermann, Christian

    2015-01-01

    Membrane fusion at vacuoles requires a consecutive action of the HOPS tethering complex, which is recruited by the Rab GTPase Ypt7, and vacuolar SNAREs to drive membrane fusion. It is assumed that the Sec1/Munc18-like Vps33 within the HOPS complex is largely responsible for SNARE chaperoning. Here, we present direct evidence for HOPS binding to SNAREs and the Habc domain of the Vam3 SNARE protein, which may explain its function during fusion. We show that HOPS interacts strongly with the Vam3 Habc domain, assembled Q-SNAREs, and the R-SNARE Ykt6, but not the Q-SNARE Vti1 or the Vam3 SNARE domain. Electron microscopy combined with Nanogold labeling reveals that the binding sites for vacuolar SNAREs and the Habc domain are located in the large head of the HOPS complex, where Vps16 and Vps33 have been identified before. Competition experiments suggest that HOPS bound to the Habc domain can still interact with assembled Q-SNAREs, whereas Q-SNARE binding prevents recognition of the Habc domain. In agreement, membranes carrying Vam3ΔHabc fuse poorly unless an excess of HOPS is provided. These data suggest that the Habc domain of Vam3 facilitates the assembly of the HOPS/SNARE machinery at fusion sites and thus supports efficient membrane fusion. PMID:25564619

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

    PubMed

    Fellner, Johann; Brunner, Paul H

    2010-11-01

    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(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(s)=300 m/d) and zero retention capacity, while the bulk of the landfill (matrix domain) is characterized by low permeability (K(s)=0.1m/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. PMID:20385480

  14. Inhibitory spillover: increased urination urgency facilitates impulse control in unrelated domains.

    PubMed

    Tuk, Mirjam A; Trampe, Debra; Warlop, Luk

    2011-05-01

    Visceral states are known to reduce the ability to exert self-control. In the current research, we investigated how self-control is affected by a visceral factor associated with inhibition rather than with approach: bladder control. We designed four studies to test the hypothesis that inhibitory signals are not domain-specific but can spill over to unrelated domains, resulting in increased impulse control in the behavioral domain. In Study 1, participants' urination urgency correlated with performance on color-naming but not word-meaning trials of a Stroop task. In Studies 2 and 3, we found that higher levels of bladder pressure resulted in an increased ability to resist impulsive choices in monetary decision making. We found that inhibitory spillover effects are moderated by sensitivity of the Behavioral Inhibition System (Study 3) and can be induced by exogenous cues (Study 4). Implications for inhibition and impulse-control theories are discussed.

  15. Inhibitory spillover: increased urination urgency facilitates impulse control in unrelated domains.

    PubMed

    Tuk, Mirjam A; Trampe, Debra; Warlop, Luk

    2011-05-01

    Visceral states are known to reduce the ability to exert self-control. In the current research, we investigated how self-control is affected by a visceral factor associated with inhibition rather than with approach: bladder control. We designed four studies to test the hypothesis that inhibitory signals are not domain-specific but can spill over to unrelated domains, resulting in increased impulse control in the behavioral domain. In Study 1, participants' urination urgency correlated with performance on color-naming but not word-meaning trials of a Stroop task. In Studies 2 and 3, we found that higher levels of bladder pressure resulted in an increased ability to resist impulsive choices in monetary decision making. We found that inhibitory spillover effects are moderated by sensitivity of the Behavioral Inhibition System (Study 3) and can be induced by exogenous cues (Study 4). Implications for inhibition and impulse-control theories are discussed. PMID:21467548

  16. 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

  17. 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.

  18. 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.

  19. The Collagen Receptor Discoidin Domain Receptor 2 Stabilizes Snail1 Protein to Facilitate Breast Cancer Metastasis

    PubMed Central

    Zhang, Kun; Corsa, Callie A.; Ponik, Suzanne M.; Prior, Julie L.; Piwnica-Worms, David; Eliceiri, Kevin W.; Keely, Patricia J.; Longmore, Gregory D.

    2013-01-01

    Increased stromal collagen deposition in human breast tumours correlates with metastases. We show that activation of the collagen I receptor DDR2 regulates Snail1 protein stability by stimulating ERK2 activity, in a Src-dependent manner. Activated ERK2 directly phosphorylates Snail1, leading to Snail1 nuclear accumulation, reduced ubiquitination, and increased protein half-life. DDR2-mediated stabilization of Snail1 promotes breast cancer cell invasion and migration in vitro, and metastasis in vivo. DDR2 expression was observed in the majority of human invasive ductal breast carcinomas studied, and was associated with nuclear Snail1 and absence of E-cadherin expression. We propose that DDR2 maintains Snail1 protein level and activity in tumor cells that have undergone EMT, thereby facilitating continued tumor cell invasion through collagen I-rich ECM by sustaining the EMT phenotype. As such, DDR2 could be an RTK target for the treatment of breast cancer metastasis. PMID:23644467

  20. Leveraging Domain Knowledge to Facilitate Visual Exploration of Large Population Datasets

    PubMed Central

    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. PMID:24551363

  1. 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

  2. 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.

  3. The discoidin domain receptor 1 gene has a functional A2RE sequence.

    PubMed

    Roig, Barbara; Moyano, Sílvia; Martorell, Lourdes; Costas, Javier; Vilella, Elisabet

    2012-02-01

    Discoidin domain receptor 1 (DDR1) is expressed in myelin oligodendrocytes and co-localizes with myelin basic protein (MBP). Alternative splicing of DDR1 generates five isoforms designated DDR1a-e. The MBP mRNA contains an hnRNP A2 response element (A2RE) sequence that is recognized by heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1, which is responsible for transport of the MBP mRNA to oligodendrocyte processes. We hypothesized that DDR1 could have a functional A2RE sequence. By in silico analysis, we identified an A2RE-like sequence in the human DDR1 mRNA. We observed nuclear and dendrite cytoplasmic immunofluorescence, indicating that DDR1 and hnRNP A2/B1 co-localize in human oligodendrocytes and in differentiated HOG16 cells. The A2RE-like sequence of DDR1 contains the single nucleotide polymorphism rs2267641, and we found that in the human brain, the minor allele is associated with lower and higher levels DDR1b and DDR1c mRNA expression, respectively. Moreover, a positive correlation between DDR1c and the myelin genes myelin-associated glycoprotein and oligodendrocyte lineage transcription factor 2 was found. Differentiated HOG16 cells transfected with an hnRNP A2/B1 siRNA simultaneously show a decrease and an increase in the DDR1c and DDR1b mRNA expression levels, respectively, which was accompanied by a decrease in DDR1 protein levels at the cytoplasmic edges. These results suggest that the DDR1 A2RE sequence is functionally involved in the hnRNP A2/B1-mediated splicing and transport of the DDR1c mRNA.

  4. Transactivation domains facilitate promoter occupancy for the dioxin-inducible CYP1A1 gene in vivo.

    PubMed Central

    Ko, H P; Okino, S T; Ma, Q; Whitlock, J P

    1997-01-01

    We have studied the transcriptional regulation of the dioxin-inducible mouse CYP1A1 gene in its native chromosomal setting. We analyzed the ability of aromatic hydrocarbon receptor (AhR) mutants and AhR chimeras to restore dioxin responsiveness to the CYP1A1 gene in AhR-defective mouse hepatoma cells. Our data reveal that transactivation domains in AhR's C-terminal half mediate occupancy of the nuclear factor 1 site and TATA box for the CYP1A1 promoter in vivo. Transactivation domains of VP16 and AhR nuclear translocator, but not Sp1, can substitute for AhR's C-terminal half in facilitating protein binding at the promoter. Our data also reveal an apparent linear relationship between promoter occupancy and CYP1A1 gene expression in chromatin. These findings provide new insights into the in vivo mechanism of transcriptional activation for an interesting mammalian gene. PMID:9199285

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. The Basic Domain of Herpes Simplex Virus 1 pUS9 Recruits Kinesin-1 To Facilitate Egress from Neurons

    PubMed Central

    Davis, April; Miranda-Saksena, Monica; Fernandez, Marian A.; Kelly, Barbara J.; Jones, Cheryl A.; LaVail, Jennifer H.; Xue, Jing; Lai, Joey

    2015-01-01

    ABSTRACT The alphaherpesviral envelope protein pUS9 has been shown to play a role in the anterograde axonal transport of herpes simplex virus 1 (HSV-1), yet the molecular mechanism is unknown. To address this, we used an in vitro pulldown assay to define a series of five arginine residues within the conserved pUS9 basic domain that were essential for binding the molecular motor kinesin-1. The mutation of these pUS9 arginine residues to asparagine blocked the binding of both recombinant and native kinesin-1. We next generated HSV-1 with the same pUS9 arginine residues mutated to asparagine (HSV-1pUS9KBDM) and then restored them being to arginine (HSV-1pUS9KBDR). The two mutated viruses were analyzed initially in a zosteriform model of recurrent cutaneous infection. The primary skin lesion scores were identical in severity and kinetics, and there were no differences in viral load at dorsal root ganglionic (DRG) neurons at day 4 postinfection (p.i.) for both viruses. In contrast, HSV-1pUS9KBDM showed a partial reduction in secondary skin lesions at day 8 p.i. compared to the level for HSV-1pUS9KBDR. The use of rat DRG neuronal cultures in a microfluidic chamber system showed both a reduction in anterograde axonal transport and spread from axons to nonneuronal cells for HSV-1pUS9KBDM. Therefore, the basic domain of pUS9 contributes to anterograde axonal transport and spread of HSV-1 from neurons to the skin through recruitment of kinesin-1. IMPORTANCE Herpes simplex virus 1 and 2 cause genital herpes, blindness, encephalitis, and occasionally neonatal deaths. There is also increasing evidence that sexually transmitted genital herpes increases HIV acquisition, and the reactivation of HSV increases HIV replication and transmission. New antiviral strategies are required to control resistant viruses and to block HSV spread, thereby reducing HIV acquisition and transmission. These aims will be facilitated through understanding how HSV is transported down nerves and into

  10. LIM domain only 2 over-expression in prostate stromal cells facilitates prostate cancer progression through paracrine of Interleukin-11

    PubMed Central

    Ruan, Yuan; Wang, Xiao-Hai; Zhao, Wei; Wang, Xing-Jie; Zhu, Yi-Ping; Gao, Yuan; Hao, Kui-Yuan; Chen, Lei; Han, Bang-Min; Xia, Shu-Jie; Zhao, Fu-Jun

    2016-01-01

    Mechanisms of stromal-epithelial crosstalk are essential for Prostate cancer (PCa) tumorigenesis and progression. Peripheral zone of the prostate gland possesses a stronger inclination for PCa than transition zone. We previously found a variety of genes that differently expressed among different prostate stromal cells, including LIM domain only 2 (LMO2) which highly expressed in peripheral zone derived stromal cells (PZSCs) and PCa associated fibroblasts (CAFs) compared to transition zone derived stromal cells (TZSCs). Studies on its role in tumors have highlighted LMO2 as an oncogene. Herein, we aim to study the potential mechanisms of stromal LMO2 in promoting PCa progression. The in vitro cells co-culture and in vivo cells recombination revealed that LMO2 over-expressed prostate stromal cells could promote the proliferation and invasiveness of either prostate epithelial or cancer cells. Further protein array screening confirmed that stromal LMO2 stimulated the secretion of Interleukin-11 (IL-11), which could promote proliferation and invasiveness of PCa cells via IL-11 receptor α (IL11Rα) – STAT3 signaling. Moreover, stromal LMO2 over-expression could suppress miR-204-5p which was proven to be a negative regulator of IL-11 expression. Taken together, results of our study demonstrate that prostate stromal LMO2 is capable of stimulating IL-11 secretion and by which activates IL11Rα – STAT3 signaling in PCa cells and then facilitates PCa progression. These results may make stromal LMO2 responsible for zonal characteristic of PCa and as a target for PCa microenvironment-targeted therapy. PMID:27028859

  11. Viral fusion protein transmembrane domain adopts β-strand structure to facilitate membrane topological changes for virus-cell fusion.

    PubMed

    Yao, Hongwei; Lee, Michelle W; Waring, Alan J; Wong, Gerard C L; Hong, Mei

    2015-09-01

    The C-terminal transmembrane domain (TMD) of viral fusion proteins such as HIV gp41 and influenza hemagglutinin (HA) is traditionally viewed as a passive α-helical anchor of the protein to the virus envelope during its merger with the cell membrane. The conformation, dynamics, and lipid interaction of these fusion protein TMDs have so far eluded high-resolution structure characterization because of their highly hydrophobic nature. Using magic-angle-spinning solid-state NMR spectroscopy, we show that the TMD of the parainfluenza virus 5 (PIV5) fusion protein adopts lipid-dependent conformations and interactions with the membrane and water. In phosphatidylcholine (PC) and phosphatidylglycerol (PG) membranes, the TMD is predominantly α-helical, but in phosphatidylethanolamine (PE) membranes, the TMD changes significantly to the β-strand conformation. Measured order parameters indicate that the strand segments are immobilized and thus oligomerized. (31)P NMR spectra and small-angle X-ray scattering (SAXS) data show that this β-strand-rich conformation converts the PE membrane to a bicontinuous cubic phase, which is rich in negative Gaussian curvature that is characteristic of hemifusion intermediates and fusion pores. (1)H-(31)P 2D correlation spectra and (2)H spectra show that the PE membrane with or without the TMD is much less hydrated than PC and PG membranes, suggesting that the TMD works with the natural dehydration tendency of PE to facilitate membrane merger. These results suggest a new viral-fusion model in which the TMD actively promotes membrane topological changes during fusion using the β-strand as the fusogenic conformation.

  12. Generation of enhanced stability factor VIII variants by replacement of charged residues at the A2 domain interface.

    PubMed

    Wakabayashi, Hironao; Varfaj, Fatbardha; Deangelis, Jennifer; Fay, Philip J

    2008-10-01

    Factor VIII consists of a heavy chain (A1A2B domains) and light chain (A3C1C2 domains), whereas the contiguous A1A2 domains are separate subunits in the cofactor, factor VIIIa. The intrinsic instability of the cofactor results from weak affinity interactions of the A2 subunit within factor VIIIa. The charged residues Glu272, Asp519, Glu665, and Glu1984 appear buried at the interface of the A2 domain with either the A1 or A3 domain, and thus may impact protein stability. To determine the effects of these residues on procofactor/cofactor stability, these residues were individually replaced with either Ala or Val, and stable BHK cell lines expressing the B-domainless proteins were prepared. Specific activity and thrombin generation parameters for 7 of the 8 variants were more than 80% the wild-type value. Factor VIII activity at 52 degrees C to 60 degrees C and the decay of factor VIIIa activity after thrombin activation were monitored. Six of the 7 variants showing wild-type-like activity demonstrated enhanced stability, with the Glu1984Val variant showing a 2-fold increase in thermostability and an approximately 4- to 8-fold increase in stability of factor VIIIa. These results indicate that replacement of buried charged residues is an effective alternative to covalent modification in increasing factor VIII (VIIIa) stability. PMID:18650448

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

    PubMed

    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

  14. 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

  15. 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.

  16. The central domain of yeast transcription factor Rpn4 facilitates degradation of reporter protein in human cells.

    PubMed

    Morozov, A V; Spasskaya, D S; Karpov, D S; Karpov, V L

    2014-10-16

    Despite high interest in the cellular degradation machinery and protein degradation signals (degrons), few degrons with universal activity along species have been identified. It has been shown that fusion of a target protein with a degradation signal from mammalian ornithine decarboxylase (ODC) induces fast proteasomal degradation of the chimera in both mammalian and yeast cells. However, no degrons from yeast-encoded proteins capable to function in mammalian cells were identified so far. Here, we demonstrate that the yeast transcription factor Rpn4 undergoes fast proteasomal degradation and its central domain can destabilize green fluorescent protein and Alpha-fetoprotein in human HEK 293T cells. Furthermore, we confirm the activity of this degron in yeast. Thus, the Rpn4 central domain is an effective interspecies degradation signal.

  17. Transmembrane domain V plays a stabilizing role in the function of human bile acid transporter SLC10A2.

    PubMed

    Moore, Robyn H; Chothe, Paresh; Swaan, Peter W

    2013-07-30

    The human apical sodium-dependent bile acid transporter (hASBT, SLC10A2), primarily expressed in the ileum, is involved in both the recycling of bile acids and cholesterol homeostasis. In this study, the structure-function relationship of transmembrane domain 5 (TM5) residues involved in transport is elucidated. Cysteine scanning mutagenesis of each consecutive residue on TM5 resulted in 96% of mutants having a significantly decreased transport activity, although each was expressed at the cell surface. Specifically, G197 and I208 were no longer functional, and G201 and G212 functioned at a level of <10% upon cysteine mutation. Interestingly, each of these exists along one face of the helix. Studies suggest that neither G201 nor G212 is on the substrate pathway. Conservative alanine mutations of the four residues displayed a higher activity in all but G197A, indicating its functional importance. G197 and G201 form a GxxxG motif, which has been found to be important in helix-helix interactions. According to our model, G197 and G201 face transmembrane domain 4 (TM4) residues G179 and P175, respectively. Similarly, G212 faces G237, which forms part of a GxxxG domain in transmembrane domain 6 (TM6). It is possible that these GxxxG domains and their interacting partners are responsible for maintaining the structure of the helices and their interactions with one another. I205 and I208 are both in positions to anchor the GxxxG domains and direct the change in interaction of TM5 from TM4 to TM6. Combined, the results suggest that residues along TM5 are critical for ASBT function but are not directly involved in substrate translocation.

  18. Isolation and Characterization of a Monobody with a Fibronectin Domain III Scaffold That Specifically Binds EphA2.

    PubMed

    Park, Seung-Hwan; Park, Sukho; Kim, Dong-Yeon; Pyo, Ayoung; Kimura, Richard H; Sathirachinda, Ataya; Choy, Hyon E; Min, Jung-Joon; Gambhir, Sanjiv Sam; Hong, Yeongjin

    2015-01-01

    Monobodies are binding scaffold proteins originating from a human fibronectin domain III (Fn3) scaffold that can be easily engineered with specificity and affinity. Human EphA2 (hEphA2) is an early detection marker protein for various tumors including lung, breast, and colon cancer. In this study, we isolated two hEphA2-specific monobodies (E1 and E10) by screening a yeast surface display library. They showed the same amino acid sequence except in the DE loop and had high affinity (~2 nM Kd) against hEphA2. E1 bound only hEphA2 and mEphA2, although it bound hEphA2 with an affinity 2-fold higher than that of mEphA2. However, E10 also bound the mEphA6 and mEphA8 homologs as well as hEphA2 and mEphA2. Thus, E1 but not E10 was highly specific for hEphA2. E1 specifically bound human cells and xenograft tumor tissues expressing hEphA on the cell surface. In vivo optical imaging showed strong targeting of Cy5.5-labeled E1 to mouse tumor tissue induced by PC3 cells, a human prostate cancer cell line that expresses a high level of hEphA2. In conclusion, the highly specific monobody E1 is useful as a hEphA2 probe candidate for in vivo diagnosis and therapy. PMID:26177208

  19. N-terminal domain of the V-ATPase a2-subunit displays integral membrane protein properties.

    PubMed

    Merkulova, Maria; McKee, Mary; Dip, Phat Vinh; Grüber, Gerhard; Marshansky, Vladimir

    2010-10-01

    V-ATPase is a multisubunit membrane complex that functions as nanomotor coupling ATP hydrolysis with proton translocation across biological membranes. Recently, we uncovered details of the mechanism of interaction between the N-terminal tail of the V-ATPase a2-subunit isoform (a2N(1-402)) and ARNO, a GTP/GDP exchange factor for Arf-family small GTPases. Here, we describe the development of two methods for preparation of the a2N(1-402) recombinant protein in milligram quantities sufficient for further biochemical, biophysical, and structural studies. We found two alternative amphiphilic chemicals that were required for protein stability and solubility during purification: (i) non-detergent sulfobetaine NDSB-256 and (ii) zwitterionic detergent FOS-CHOLINE®12 (FC-12). Moreover, the other factors including mild alkaline pH, the presence of reducing agents and the absence of salt were beneficial for stabilization and solubilization of the protein. A preparation of a2N(1-402) in NDSB-256 was successfully used in pull-down and BIAcore™ protein-protein interaction experiments with ARNO, whereas the purity and quality of the second preparation in FC-12 was validated by size-exclusion chromatography and CD spectroscopy. Surprisingly, the detergent requirement for stabilization and solubilization of a2N(1-402) and its cosedimentation with liposomes were different from peripheral domains of other transmembrane proteins. Thus, our data suggest that in contrast to current models, so called "cytosolic" tail of the a2-subunit might actually be embedded into and/or closely associated with membrane phospholipids even in the absence of any obvious predicted transmembrane segments. We propose that a2N(1-402) should be categorized as an integral monotopic domain of the a2-subunit isoform of the V-ATPase.

  20. 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.

  1. Transmembrane domain II of the human bile acid transporter SLC10A2 coordinates sodium translocation.

    PubMed

    Sabit, Hairat; Mallajosyula, Sairam S; MacKerell, Alexander D; Swaan, Peter W

    2013-11-01

    Human apical sodium-dependent bile acid transporter (hASBT, SLC10A2) is responsible for intestinal reabsorption of bile acids and plays a key role in cholesterol homeostasis. We used a targeted and systematic approach to delineate the role of highly conserved transmembrane helix 2 on the expression and function of hASBT. Cysteine mutation significantly depressed transport activity for >60% of mutants without affecting cell surface localization of the transporter. All mutants were inaccessible toward chemical modification by membrane-impermeant MTSET reagent, strongly suggesting that transmembrane 2 (TM2) plays an indirect role in bile acid substrate translocation. Both bile acid uptake and sodium dependence of TM2 mutants revealed a distinct α-helical periodicity. Kinetic studies with conservative and non-conservative mutants of sodium sensitive residues further underscored the importance of Gln(75), Phe(76), Met(79), Gly(83), Leu(86), Phe(90), and Asp(91) in hASBT function. Computational analysis indicated that Asp(91) may coordinate with sodium during the transport cycle. Combined, our data propose that a consortium of sodium-sensitive residues along with previously reported residues (Thr(134), Leu(138), and Thr(149)) from TM3 may form the sodium binding and translocation pathway. Notably, residues Gln(75), Met(79), Thr(82), and Leu(86) from TM2 are highly conserved in TM3 of a putative remote bacterial homologue (ASBTNM), suggesting a universal mechanism for the SLC10A transporter family.

  2. Inhibition of alloreactive cytotoxic T lymphocytes by peptides from the alpha 2 domain of HLA-A2.

    PubMed

    Parham, P; Clayberger, C; Zorn, S L; Ludwig, D S; Schoolnik, G K; Krensky, A M

    Class I major histocompatibility complex (MHC) molecules function in the recognition of antigens by cytotoxic T lymphocytes (CTL). Although this biological role is firmly established and much has been learnt about their structure and polymorphic variation, little is known of the regions of class I molecules that are involved in functional interactions with components of the T-cell surface. Here we show that peptides derived from residues 98-113 of the alpha 2 domain of HLA-A2 specifically inhibit the recognition of target cells by many HLA-A2-specific CTL. In addition to identifying a region that is probably involved in binding the T-cell receptor these results raise the possibility that alloreactive CTL may recognize degraded fragments of class I histocompatibility antigens. PMID:2433598

  3. Implementation of pregnancy weight management and obesity guidelines: a meta-synthesis of healthcare professionals' barriers and facilitators using the Theoretical Domains Framework.

    PubMed

    Heslehurst, N; Newham, J; Maniatopoulos, G; Fleetwood, C; Robalino, S; Rankin, J

    2014-06-01

    Obesity in pregnancy is rising and is associated with severe health consequences for both the mother and the child. There is an increasing international focus on guidelines to manage the clinical risks of maternal obesity, and for pregnancy weight management. However, passive dissemination of guidelines is not effective and more active strategies are required for effective guideline implementation into practice. Implementation of guidelines is a form of healthcare professional behaviour change, and therefore implementation strategies should be based on appropriate behaviour change theory. This systematic review aimed to identify the determinants of healthcare professionals' behaviours in relation to maternal obesity and weight management. Twenty-five studies were included. Data synthesis of the existing international qualitative and quantitative evidence base used the Theoretical Domains Framework to identify the barriers and facilitators to healthcare professionals' maternal obesity and weight management practice. The domains most frequently identified included 'knowledge', 'beliefs about consequences' and 'environmental context and resources'. Healthcare professionals' weight management practice had the most barriers compared with any other area of maternal obesity practice. The results of this review will be used to inform the development of an intervention to support healthcare professional behaviour change.

  4. Enhanced factor VIIIa stability of A2 domain interface variants results from an increased apparent affinity for the A2 subunit. Results from an increased apparent affinity for the A2 subunit.

    PubMed

    Monaghan, M; Wakabayashi, H; Griffiths, A; Wintermute, J; Fay, P J

    2014-09-01

    Factor (F)VIIIa, a heterotrimer comprised of A1, A2, and A3C1C2 subunits, is labile due to the tendency of the A2 subunit to dissociate from the A1/A3C1C2 dimer. As dissociation of the A2 subunit inactivates FVIIIa activity, retention of A2 defines FVIIIa stability and thus, FXase activity. Earlier results showed that replacing residues D519, E665, and E1984 at the A2 domain interface with Ala or Val reduced rates of FVIIIa decay, increasing FXa and thrombin generation. We now show the enhanced FVIIIa stability of these variants results from increases in inter-A2 subunit affinity. Using a FVIIIa reconstitution assay to monitor inter-subunit affinity by activity regeneration, the apparent Kd value for the interaction of wild-type (WT) A2 subunit with WT A1/A3C1C2 dimer (43 ± 2 nM) was significantly higher than values observed for the A2 point mutants D519A/V, E665A/V, and E1984A/V which ranged from ~5 to ~19 nM. Val was determined to be the optimal hydrophobic residue at position 665 (apparent Kd = 5.1 ± 0.7 nM) as substitutions with Ile or Leu at this position increased the apparent Kd value by ~3- and ~7-fold, respectively. Furthermore, the double mutant (D519V/E665V) showed an ~47-fold lower apparent Kd value (0.9 ± 0.6 nM) than WT. Thus these hydrophobic mutations at the A2 subunit interfaces result in high binding affinities for the A2 subunit and correlate well with previously observed reductions in rates in FVIIIa decay. PMID:24899227

  5. 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

    2005-09-01

    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.

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

    PubMed

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

    2016-02-12

    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

  7. Interfacial membrane docking of cytosolic phospholipase A2 C2 domain using electrostatic potential-modulated spin relaxation magnetic resonance

    PubMed Central

    Ball, Andy; Nielsen, Robert; Gelb, Michael H.; Robinson, Bruce H.

    1999-01-01

    The C2 domain of cytosolic phospholipase A2 (C2cPLA2) plays an important role in calcium-dependent transfer of the protein from the cytosol to internal cellular membranes as a prelude for arachidonate release from membrane phospholipids. By using a recently developed electron paramagnetic resonance approach together with 13 site-specifically nitroxide spin labeled C2cPLA2s and membrane-permeant and -impermeant spin relaxants, we have determined the orientation of C2cPLA2 with respect to the surface of vesicles of the phospholipid 1,2-dioleoyl-sn-glycero-3-phosphomethanol. The structure reveals that the two calcium-binding regions on C2cPLA2 that display hydrophobic residues, CBR1 and CBR3, are partially inserted into the core of the membrane. CBR2 that contains predominantly hydrophilic residues is close to the membrane but not inserted. The long axis of the cylindrical C2cPLA2 molecule is tilted with respect to the bilayer normal, which brings a cluster of basic protein residues close to the phospholipid headgroups. Such an orientation places the two bound calcium ions close to the membrane surface. All together, the results provide structural support for previous proposals that binding of C2cPLA2 to the membrane interface is driven in part by insertion of hydrophobic surface loops into the membrane core. The results are contrasted with previous studies of the interfacial binding of the first C2 domain of synaptotagmin I, which has shorter surface loops that display basic residues for electrostatic interaction with the bilayer surface. PMID:10359764

  8. 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.

  9. Bombyx Y-box protein BYB facilitates specific DNA interaction of various DNA binding proteins independently of the cold shock domain.

    PubMed

    Takiya, Shigeharu; Nishita, Yoshinori; Ishikawa, Susumu; Ohno, Kaoru; Tamura, Taka-aki; Suzuki, Yoshiaki

    2004-06-01

    A new member of the Y-box protein family of the silkworm Bombyx mori (BYB) was co-purified with the fibroin gene enhancer-binding protein FMBP-1, and stimulated the binding of FMBP-1 to its cognate DNA element. However, the stimulatory effect was not specific to FMBP-1, BYB also enhancing the binding of mammalian transcription factors OTF2, SP1 and AP2 to their specific binding elements. Besides the above transcription regulatory factors, BYB facilitated the binding of basal transcription factor TBP, and enhanced transcription from the adenovirus 2 major late promoter in a reconstituted transcription system. Moreover, BYB stimulated the reactions of some restriction endonucleases under cold conditions. The C-terminal region of BYB was sufficient for these stimulatory effects, and the highly conserved cold shock domain (CSD) in the N-terminal region was dispensable. GST-pull down experiments showed that the C-terminal region could interact with DNA independently of the CSD. The above results suggest that the C-terminal region of BYB causes the active interaction of various DNA binding proteins with their targets. Such a function of the C-terminal region of BYB may partly explain the functional diversity of Y-box proteins.

  10. Enhanced Expression of T-Cell Immunoglobulin and Mucin Domain Protein 3 in Endothelial Cells Facilitates Intracellular Killing of Rickettsia heilongjiangensis.

    PubMed

    Yang, Xiaomei; Jiao, Jun; Han, Gencheng; Gong, Wenping; Wang, Pengcheng; Xiong, Xiaolu; Wen, Bohai

    2016-01-01

    Rickettsia heilongjiangensis is the pathogen of Far eastern spotted fever, and T-cell immunoglobulin and mucin domain protein 3 (Tim-3) is expressed in human vascular endothelial cells, the major target cells of rickettsiae. In the present study, we investigated the effects of altered Tim-3 expression in vivo in mice and in vitro in human endothelial cells, on day 3 after R. heilongjiangensis infection. Compared with corresponding controls, rickettsial burdens both in vivo and in vitro were significantly higher with blocked Tim-3 signaling or silenced Tim-3 and significantly lower with overexpressed Tim-3. Additionally, the expression of inducible nitric oxide synthase and interferon γ in endothelial cells with blocked Tim-3 signaling or silenced Tim-3 was significantly lower, while the expression of inducible nitric oxide synthase, interferon γ, and tumor necrosis factor α in transgenic mice with Tim-3 overexpression was significantly higher. These results reveal that enhanced Tim-3 expression facilitates intracellular rickettsial killing in a nitric oxide-dependent manner in endothelial cells during the early phase of rickettsial infection.

  11. Major facilitator superfamily domain-containing protein 2a (MFSD2A) has roles in body growth, motor function, and lipid metabolism.

    PubMed

    Berger, Justin H; Charron, Maureen J; Silver, David L

    2012-01-01

    The metabolic adaptations to fasting in the liver are largely controlled by the nuclear hormone receptor peroxisome proliferator-activated receptor alpha (PPARα), where PPARα upregulates genes encoding the biochemical pathway for β-oxidation of fatty acids and ketogenesis. As part of an effort to identify and characterize nutritionally regulated genes that play physiological roles in the adaptation to fasting, we identified Major facilitator superfamily domain-containing protein 2a (Mfsd2a) as a fasting-induced gene regulated by both PPARα and glucagon signaling in the liver. MFSD2A is a cell-surface protein homologous to bacterial sodium-melibiose transporters. Hepatic expression and turnover of MFSD2A is acutely regulated by fasting/refeeding, but expression in the brain is constitutive. Relative to wildtype mice, gene-targeted Mfsd2a knockout mice are smaller, leaner, and have decreased serum, liver and brown adipose triglycerides. Mfsd2a knockout mice have normal liver lipid metabolism but increased whole body energy expenditure, likely due to increased β-oxidation in brown adipose tissue and significantly increased voluntary movement, but surprisingly exhibited a form of ataxia. Together, these results indicate that MFSD2A is a nutritionally regulated gene that plays myriad roles in body growth and development, motor function, and lipid metabolism. Moreover, these data suggest that the ligand(s) that are transported by MFSD2A play important roles in these physiological processes and await future identification. PMID:23209793

  12. 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

  13. A subset of high-titer anti-factor VIII A2 domain antibodies is responsive to treatment with factor VIII.

    PubMed

    Eubanks, Joshua; Baldwin, W Hunter; Markovitz, Rebecca; Parker, Ernest T; Cox, Courtney; Kempton, Christine L; Meeks, Shannon L

    2016-04-21

    The primary B-cell epitopes of factor VIII (fVIII) are in the A2 and C2 domains. Within the C2 domain, antibody epitope and kinetics are more important than inhibitor titer in predicting pathogenicity in a murine bleeding model. To investigate this within the A2 domain, the pathogenicity of a diverse panel of antihuman fVIII A2 domain monoclonal antibodies (MAbs) was tested in the murine model. MAbs were injected into hemophilia A mice, followed by injection of human B domain-deleted fVIII. Blood loss after a 4-mm tail snip was measured. The following anti-A2 MAbs were tested: high-titer type 1 inhibitors 4A4, 2-76, and 1D4; 2-54, a high-titer type 2 inhibitor; B94, a type 2 inhibitor; and noninhibitory MAbs GMA-012, 4C7, and B25. All high-titer type 1 MAbs produced blood loss that was significantly greater than control mice, whereas all non-inhibitory MAbs produced blood loss that was similar to control. The type 2 MAbs were not pathogenic despite 2-54 having an inhibitor titer of 34 000 BU/mg immunoglobulin G. In addition, a patient with a high-titer type 2 anti-A2 inhibitor who is responsive to fVIII is reported. The discrepancy between inhibitor titer and bleeding phenotype combined with similar findings in the C2 domain stress the importance of inhibitor properties not detected in the standard Bethesda assay in predicting response to fVIII therapy.

  14. Adenosine A(2A) receptor antagonists are broad facilitators of antinicotinic neuromuscular blockade monitored either with 2 Hz train-of-four or 50 Hz tetanic stimuli.

    PubMed

    Pereira, Monalisa W; Correia-de-Sá, Paulo; Alves-Do-Prado, Wilson

    2012-10-01

    1. The 2 Hz train-of-four ratio (TOF(ratio)) is used to monitor the degree of patient curarization. Using a rat phrenic nerve-hemidiaphragm preparation, we showed that antinicotinic agents, such as hexamethonium, d-tubocurarine and pancuronium, but not cisatracurium, decreased contractions produced by physiological nerve activity patterns (50 Hz) more efficiently than those caused by 2 Hz trains. Uncertainty about the usefulness of the TOF(ratio) to control safe recovery from curarization prompted us to investigate the muscarinic and adenosine neuromodulation of tetanic (50 Hz) fade induced by antinicotinic agents at concentrations that cause a 25% reduction in the TOF(ratio) (TOF(fade)). 2. Tetanic fade caused by d-tubocurarine (1.1 μmol/L), pancuronium (3 μmol/L) and hexamethonium (5.47 mmol/L) was attenuated by blocking presynaptic inhibitory muscarinic M(2) and adenosine A(1) receptors with methoctramine (1 μmol/L) and 1,3-dipropyl-8-cyclopentylxanthine (2.5 nmol/L), respectively. These compounds enhanced rather than decreased tetanic fade induced by cisatracurium (2.2 μmol/L), but they consistently attenuated cisatracurium-induced TOF(fade). The effect of the M(1) receptor antagonist pirenzepine (10 nmol/L) on fade produced by antinicotinic agents at 50 Hz was opposite to that observed with TOF stimulation. Blockade of adenosine A(2A) receptors with ZM 241385 (10 nmol/L) attenuated TOF(fade) caused by all antinicotinic drugs tested, with the exception of the 'pure' presynaptic nicotinic antagonist hexamethonium. ZM 241385 was the only compound tested in this series that facilitated recovery from tetanic fade produced by cisatracurium. 3. The data suggest that distinct antinicotinic relaxants interfere with fine-tuning neuromuscular adaptations to motor nerve stimulation patterns via activation of presynaptic muscarinic and adenosine receptors. These results support the use of A(2A) receptor antagonists together with atropine to facilitate recovery from

  15. Fusion proteins containing the A2 domain of cholera toxin assemble with B polypeptides of cholera toxin to form immunoreactive and functional holotoxin-like chimeras.

    PubMed Central

    Jobling, M G; Holmes, R K

    1992-01-01

    Cholera enterotoxin (CT) is produced by Vibrio cholerae and excreted into the culture medium as an extracellular protein. CT consists of one A polypeptide and five B polypeptides associated by noncovalent bonds, and CT-B interacts with CT-A primarily via the A2 domain. Treatment of CT with trypsin cleaves CT-A into A1 and A2 fragments that are linked by a disulfide bond. CT-B binds to ganglioside GM1, which functions as the plasma membrane receptor for CT, and the enzymatic activity of A1 causes the toxic effects of CT on target cells. We constructed translational fusions that joined foreign proteins via their carboxyl termini to the A2 domain of CT-A, and we studied the interactions of the fusion proteins with CT-B. The A2 domain was necessary and sufficient to enable bacterial alkaline phosphatase (BAP), maltose-binding protein (MBP) or beta-lactamase (BLA) to associate with CT-B to form stable, immunoreactive, holotoxin-like chimeras. Each holotoxin-like chimera was able to bind to ganglioside GM1. Holotoxin-like chimeras containing the BAP-A2 and BLA-A2 fusion proteins had BAP activity and BLA activity, respectively. We constructed BAP-A2 mutants with altered carboxyl-terminal sequences and tested their ability to assemble into holotoxin-like chimeras. Although the carboxyl-terminal QDEL sequence of the BAP-A2 fusion protein was not required for interaction with CT-B, most BAP-A2 mutants with altered carboxyl termini did not form holotoxin-like chimeras. When holotoxin-like chimeras containing BAP-A2, MBP-A2, or BLA-A2 were synthesized in V. cholerae, they were found predominantly in the periplasm. The toxin secretory apparatus of V. cholerae was not able, therefore, to translocate these holotoxin-like chimeras across the outer membrane. PMID:1399002

  16. Annexin A2 Reduces PCSK9 Protein Levels via a Translational Mechanism and Interacts with the M1 and M2 Domains of PCSK9*

    PubMed Central

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

    2014-01-01

    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. PMID:24808179

  17. An autoantibody epitope comprising residues R660, Y661, and Y665 in the ADAMTS13 spacer domain identifies a binding site for the A2 domain of VWF

    PubMed Central

    Pos, Wouter; Crawley, James T. B.; Fijnheer, Rob; Voorberg, Jan; Lane, David A.

    2010-01-01

    In the majority of patients with acquired thrombotic thrombocytopenic purpura (TTP), antibodies are directed toward the spacer domain of ADAMTS13. We have previously shown that region Y658-Y665 is involved. We now show that replacement of R660, Y661, or Y665 with alanine in ADAMTS13 reduced/abolished the binding of 2 previously isolated human monoclonal antibodies and polyclonal antibodies derived from plasma of 6 patients with acquired TTP. We investigated whether these residues also influenced cleavage of short von Willebrand factor (VWF) fragment substrate VWF115. An ADAMTS13 variant (R660A/Y661A/Y665A, ADAMTS13-RYY) showed a 12-fold reduced catalytic efficiency (kcat/Km) arising from greatly reduced (> 25-fold) binding, demonstrated by surface plasmon resonance. The influence of these residue changes on full-length VWF was determined with denaturing and flow assays. ADAMTS13-RYY had reduced activity in both, with proteolysis of VWF unaffected by autoantibody. Binding of ADAMTS13-RYY mutant to VWF was, however, similar to normal. Our results demonstrate that residues within Y658-Y665 of the ADAMTS13 spacer domain that are targeted by autoantibodies in TTP directly interact with a complementary exosite (E1660-R1668) within the VWF A2 domain. Residues R660, Y661, and Y665 are critical for proteolysis of short VWF substrates, but wider domain interactions also make important contributions to cleavage of full-length VWF. PMID:20032502

  18. Structure and function of the PWI motif: a novel nucleic acid-binding domain that facilitates pre-mRNA processing

    PubMed Central

    Szymczyna, Blair R.; Bowman, John; McCracken, Susan; Pineda-Lucena, Antonio; Lu, Ying; Cox, Brian; Lambermon, Mark; Graveley, Brenton R.; Arrowsmith, Cheryl H.; Blencowe, Benjamin J.

    2003-01-01

    The PWI motif is a highly conserved domain of unknown function in the SRm160 splicing and 3′-end cleavage-stimulatory factor, as well as in several other known or putative pre-mRNA processing components. We show here that the PWI motif is a new type of RNA/DNA-binding domain that has an equal preference for single- and double-stranded nucleic acids. Deletion of the motif prevents SRm160 from binding RNA and stimulating 3′-end cleavage, and its substitution with a heterologous RNA-binding domain restores these functions. The NMR solution structure of the SRm160-PWI motif reveals a novel, four-helix bundle and represents the first example of an α-helical fold that can bind single-stranded (ss)RNA. Structure-guided mutagenesis indicates that the same surface is involved in RNA and DNA binding and requires the cooperative action of a highly conserved, adjacent basic region. Thus, the PWI motif is a novel type of nucleic acid-binding domain that likely has multiple important functions in pre-mRNA processing, including SRm160-dependent stimulation of 3′-end formation. PMID:12600940

  19. Sluggish Cognitive Tempo and ADHD Inattention as Predictors of Externalizing, Internalizing, and Impairment Domains: A 2-Year Longitudinal Study.

    PubMed

    Bernad, Maria del Mar; Servera, Mateu; Becker, Stephen P; Burns, G Leonard

    2016-05-01

    Although sluggish cognitive tempo (SCT) is distinct from attention-deficit/hyperactivity disorder inattention (ADHD-IN), few studies have examined whether SCT longitudinally predicts other symptom or impairment dimensions. This study used 4 sources (mothers, fathers, primary teachers, and secondary teachers) and 3 occasions of measurement (first, second, and third grades) with 758 first grade (55 % boys), 718 second grade (54 % boys), and 585 third grade (53 % boys) children from Spain to determine SCT's and ADHD-IN's unique longitudinal relationships with psychopathology, academic impairment, and social impairment over the 1- and 2-year intervals (i.e., first to third grade, second to third grade). For 1- and 2-year intervals using both mothers' and fathers' ratings, higher levels of SCT uniquely predicted higher levels of anxiety, depression, academic impairment, and social impairment whereas higher levels of ADHD-IN uniquely predicted higher levels of ADHD-HI, ODD, and academic impairment. For 1- and 2-year intervals across different primary and secondary teachers (i.e., first/second and third grade ratings were provided by different teachers), higher scores on ADHD-IN uniquely predicted poorer outcomes across domains whereas higher scores on SCT uniquely predicted lower levels of ADHD-HI and ODD for both intervals in addition to higher levels of depression (for primary teachers only), academic impairment (for 1-year interval only), and peer rejection (2-year interval only for primary teachers). Overall, SCT was significantly associated with important outcomes independent of ADHD-IN over 1- and 2-year intervals and across four different raters. This study provides further evidence for distinguishing between SCT and ADHD-IN in home and school settings.

  20. 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.

  1. Cby1 promotes Ahi1 recruitment to a ring-shaped domain at the centriole-cilium interface and facilitates proper cilium formation and function.

    PubMed

    Lee, Yin Loon; Santé, Joshua; Comerci, Colin J; Cyge, Benjamin; Menezes, Luis F; Li, Feng-Qian; Germino, Gregory G; Moerner, W E; Takemaru, Ken-Ichi; Stearns, Tim

    2014-10-01

    Defects in centrosome and cilium function are associated with phenotypically related syndromes called ciliopathies. Cby1, the mammalian orthologue of the Drosophila Chibby protein, localizes to mature centrioles, is important for ciliogenesis in multiciliated airway epithelia in mice, and antagonizes canonical Wnt signaling via direct regulation of β-catenin. We report that deletion of the mouse Cby1 gene results in cystic kidneys, a phenotype common to ciliopathies, and that Cby1 facilitates the formation of primary cilia and ciliary recruitment of the Joubert syndrome protein Arl13b. Localization of Cby1 to the distal end of mature centrioles depends on the centriole protein Ofd1. Superresolution microscopy using both three-dimensional SIM and STED reveals that Cby1 localizes to an ∼250-nm ring at the distal end of the mature centriole, in close proximity to Ofd1 and Ahi1, a component of the transition zone between centriole and cilium. The amount of centriole-localized Ahi1, but not Ofd1, is reduced in Cby1(-/-) cells. This suggests that Cby1 is required for efficient recruitment of Ahi1, providing a possible molecular mechanism for the ciliogenesis defect in Cby1(-/-) cells.

  2. 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.

  3. Tumor-penetrating peptide fused EGFR single-domain antibody enhances cancer drug penetration into 3D multicellular spheroids and facilitates effective gastric cancer therapy

    PubMed Central

    Sha, Huizi; Zou, Zhengyun; Xin, Kai; Bian, Xinyu; Cai, Xueting; Lu, Wuguang; Chen, Jiao; Chen, Gang; Huang, Leaf; Blair, Andrew M.; Cao, Peng; Liu, Baorui

    2016-01-01

    Human tumors, including gastric cancer, frequently express high levels of epidermal growth factor receptors (EGFRs), which are associated with a poor prognosis. Targeted delivery of anticancer drugs to cancerous tissues shows potential in sparing unaffected tissues. However, it has been a major challenge for drug penetration in solid tumor tissues due to the complicated tumor microenvironment. We have constructed a recombinant protein named anti-EGFR-iRGD consisting of an anti-EGFR VHH (the variable domain from the heavy chain of the antibody) fused to iRGD, a tumor-specific binding peptide with high permeability. Anti-EGFR-iRGD, which targets EGFR and αvβ3, spreads extensively throughout both the multicellular spheroids and the tumor mass. The recombinant protein anti-EGFR-iRGD also exhibited antitumor activity in tumor cell lines, multicellular spheroids, and mice. Moreover, anti-EGFR-iRGD could improve anticancer drugs, such as doxorubicin (DOX), bevacizumab, nanoparticle permeability and efficacy in multicellular spheroids. This study draws attention to the importance of iRGD peptide in the therapeutic approach of anti-EGFR-iRGD. As a consequence, anti-EGFR-iRGD could be a drug candidate for cancer treatment and a useful adjunct of other anticancer drugs. PMID:25553823

  4. Omi/HtrA2 catalytic cleavage of inhibitor of apoptosis (IAP) irreversibly inactivates IAPs and facilitates caspase activity in apoptosis.

    PubMed

    Yang, Qi-Heng; Church-Hajduk, Robin; Ren, Jinyu; Newton, Michelle L; Du, Chunying

    2003-06-15

    Omi/HtrA2 is a mitochondrial serine protease that is released into the cytosol during apoptosis to antagonize inhibitors of apoptosis (IAPs) and contribute to caspase-independent cell death. Here, we demonstrate that Omi/HtrA2 directly cleaves various IAPs in vitro, and the cleavage efficiency is determined by its IAP-binding motif, AVPS. Cleavage of IAPs such as c-IAP1 substantially reduces its ability to inhibit and ubiquitylate caspases. In contrast to the stoichiometric anti-IAP activity by Smac/DIABLO, Omi/HtrA2 cleavage of c-IAP1 is catalytic and irreversible, thereby more efficiently inactivating IAPs and promoting caspase activity. Elimination of endogenous Omi by RNA interference abolishes c-IAP1 cleavage and desensitizes cells to apoptosis induced by TRAIL. In addition, overexpression of cleavage-site mutant c-IAP1 makes cells more resistant to TRAIL-induced caspase activation. This IAP cleavage by Omi is independent of caspase. Taken together, these results indicate that unlike Smac/DIABLO, Omi/HtrA2's catalytic cleavage of IAPs is a key mechanism for it to irreversibly inactivate IAPs and promote apoptosis.

  5. Role of C-terminal domain and transmembrane helices 5 and 6 in function and quaternary structure of major intrinsic proteins: analysis of aquaporin/glycerol facilitator chimeric proteins.

    PubMed

    Duchesne, Laurence; Pellerin, Isabelle; Delamarche, Christian; Deschamps, Stephane; Lagree, Valerie; Froger, Alexandrine; Bonnec, Georgette; Thomas, Daniel; Hubert, Jean-Francois

    2002-06-01

    We previously observed that aquaporins and glycerol facilitators exhibit different oligomeric states when studied by sedimentation on density gradients following nondenaturing detergent solubilization. To determine the domains of major intrinsic protein (MIP) family proteins involved in oligomerization, we constructed protein chimeras corresponding to the aquaporin AQPcic substituted in the loop E (including the proximal part of transmembrane domain (TM) 5) and/or the C-terminal part (including the distal part of TM 6) by the equivalent domain of the glycerol channel aquaglyceroporin (GlpF) (chimeras called AGA, AAG, and AGG). The analogous chimeras of GlpF were also constructed (chimeras GAG, GGA, and GAA). cRNA corresponding to all constructs were injected into Xenopus oocytes. AQPcic, GlpF, AAG, AGG, and GAG were targeted to plasma membranes. Water or glycerol membrane permeability measurements demonstrated that only the AAG chimera exhibited a channel function corresponding to water transport. Analysis of all proteins expressed either in oocytes or in yeast by velocity sedimentation on sucrose gradients following solubilization by 2% n-octyl glucoside indicated that only AQPcic and AAG exist in tetrameric forms. GlpF, GAG, and GAA sediment in a monomeric form, whereas GGA and AGG were found mono/dimeric. These data bring new evidence that, within the MIP family, aquaporins and GlpFs behave differently toward nondenaturing detergents. We demonstrate that the C-terminal part of AQPcic, including the distal half of TM 6, can be substituted by the equivalent domain of GlpF (AAG chimera) without modifying the transport specificity. Our results also suggest that interactions of TM 5 of one monomer with TM 1 of the adjacent monomer are crucial for aquaporin tetramer stability. PMID:11927589

  6. Muscarinic M(3) facilitation of acetylcholine release from rat myenteric neurons depends on adenosine outflow leading to activation of excitatory A(2A) receptors.

    PubMed

    Vieira, C; Duarte-Araújo, M; Adães, S; Magalhães-Cardoso, T; Correia-de-Sá, P

    2009-10-01

    Acetylcholine (ACh) is a major excitatory neurotransmitter in the myenteric plexus, and it regulates its own release acting via muscarinic autoreceptors. Adenosine released from stimulated myenteric neurons modulates ACh release preferentially via facilitatory A(2A) receptors. In this study, we investigated how muscarinic and adenosine receptors interplay to regulate ACh from the longitudinal muscle-myenteric plexus of the rat ileum. Blockade of the muscarinic M(2) receptor with 11-[[2-1[(diethylamino) methyl-1-piperidinyl]- acetyl

  7. The DNA methyltransferase Dnmt1 directly interacts with the SET and RING finger-associated (SRA) domain of the multifunctional protein Uhrf1 to facilitate accession of the catalytic center to hemi-methylated DNA.

    PubMed

    Berkyurek, Ahmet Can; Suetake, Isao; Arita, Kyohei; Takeshita, Kohei; Nakagawa, Atsushi; Shirakawa, Masahiro; Tajima, Shoji

    2014-01-01

    Dnmt1 is responsible for the maintenance DNA methylation during replication to propagate methylation patterns to the next generation. The replication foci targeting sequence (RFTS), which plugs the catalytic pocket, is necessary for recruitment of Dnmt1 to the replication site. In the present study we found that the DNA methylation activity of Dnmt1 was DNA length-dependent and scarcely methylated 12-bp short hemi-methylated DNA. Contrarily, the RFTS-deleted Dnmt1 and Dnmt1 mutants that destroyed the hydrogen bonds between the RFTS and catalytic domain showed significant DNA methylation activity even toward 12-bp hemi-methylated DNA. The DNA methylation activity of the RFTS-deleted Dnmt1 toward 12-bp hemi-methylated DNA was strongly inhibited on the addition of RFTS, but to a lesser extent by Dnmt1 harboring the mutations that impair the hydrogen bond formation. The SRA domain of Uhrf1, which is a prerequisite factor for maintenance methylation and selectively binds to hemi-methylated DNA, stimulated the DNA methylation activity of Dnmt1. The SRA to Dnmt1 concentration ratio was the determinant for the maximum stimulation. In addition, a mutant SRA, which had lost the DNA binding activity but was able to bind to Dnmt1, stimulated the DNA methylation activity of Dnmt1. The results indicate that the DNA methylation activity of Dnmt1 was stimulated on the direct interaction of the SRA and Dnmt1. The SRA facilitated acceptance of the 12-bp fluorocytosine-containing DNA by the catalytic center. We propose that the SRA removes the RFTS plug from the catalytic pocket to facilitate DNA acceptance by the catalytic center.

  8. The DNA Methyltransferase Dnmt1 Directly Interacts with the SET and RING Finger-associated (SRA) Domain of the Multifunctional Protein Uhrf1 to Facilitate Accession of the Catalytic Center to Hemi-methylated DNA*

    PubMed Central

    Berkyurek, Ahmet Can; Suetake, Isao; Arita, Kyohei; Takeshita, Kohei; Nakagawa, Atsushi; Shirakawa, Masahiro; Tajima, Shoji

    2014-01-01

    Dnmt1 is responsible for the maintenance DNA methylation during replication to propagate methylation patterns to the next generation. The replication foci targeting sequence (RFTS), which plugs the catalytic pocket, is necessary for recruitment of Dnmt1 to the replication site. In the present study we found that the DNA methylation activity of Dnmt1 was DNA length-dependent and scarcely methylated 12-bp short hemi-methylated DNA. Contrarily, the RFTS-deleted Dnmt1 and Dnmt1 mutants that destroyed the hydrogen bonds between the RFTS and catalytic domain showed significant DNA methylation activity even toward 12-bp hemi-methylated DNA. The DNA methylation activity of the RFTS-deleted Dnmt1 toward 12-bp hemi-methylated DNA was strongly inhibited on the addition of RFTS, but to a lesser extent by Dnmt1 harboring the mutations that impair the hydrogen bond formation. The SRA domain of Uhrf1, which is a prerequisite factor for maintenance methylation and selectively binds to hemi-methylated DNA, stimulated the DNA methylation activity of Dnmt1. The SRA to Dnmt1 concentration ratio was the determinant for the maximum stimulation. In addition, a mutant SRA, which had lost the DNA binding activity but was able to bind to Dnmt1, stimulated the DNA methylation activity of Dnmt1. The results indicate that the DNA methylation activity of Dnmt1 was stimulated on the direct interaction of the SRA and Dnmt1. The SRA facilitated acceptance of the 12-bp fluorocytosine-containing DNA by the catalytic center. We propose that the SRA removes the RFTS plug from the catalytic pocket to facilitate DNA acceptance by the catalytic center. PMID:24253042

  9. The Rab GTPase-activating protein TBC1D4/AS160 contains an atypical phosphotyrosine-binding domain that interacts with plasma membrane phospholipids to facilitate GLUT4 trafficking in adipocytes.

    PubMed

    Tan, Shi-Xiong; Ng, Yvonne; Burchfield, James G; Ramm, Georg; Lambright, David G; Stöckli, Jacqueline; James, David E

    2012-12-01

    The Rab GTPase-activating protein TBC1D4/AS160 regulates GLUT4 trafficking in adipocytes. Nonphosphorylated AS160 binds to GLUT4 vesicles and inhibits GLUT4 translocation, and AS160 phosphorylation overcomes this inhibitory effect. In the present study we detected several new functional features of AS160. The second phosphotyrosine-binding domain in AS160 encodes a phospholipid-binding domain that facilitates plasma membrane (PM) targeting of AS160, and this function is conserved in other related RabGAP/Tre-2/Bub2/Cdc16 (TBC) proteins and an AS160 ortholog in Drosophila. This region also contains a nonoverlapping intracellular GLUT4-containing storage vesicle (GSV) cargo-binding site. The interaction of AS160 with GSVs and not with the PM confers the inhibitory effect of AS160 on insulin-dependent GLUT4 translocation. Constitutive targeting of AS160 to the PM increased the surface GLUT4 levels, and this was attributed to both enhanced AS160 phosphorylation and 14-3-3 binding and inhibition of AS160 GAP activity. We propose a model wherein AS160 acts as a regulatory switch in the docking and/or fusion of GSVs with the PM.

  10. The Rab GTPase-Activating Protein TBC1D4/AS160 Contains an Atypical Phosphotyrosine-Binding Domain That Interacts with Plasma Membrane Phospholipids To Facilitate GLUT4 Trafficking in Adipocytes

    PubMed Central

    Tan, Shi-Xiong; Ng, Yvonne; Burchfield, James G.; Ramm, Georg; Lambright, David G.; Stöckli, Jacqueline

    2012-01-01

    The Rab GTPase-activating protein TBC1D4/AS160 regulates GLUT4 trafficking in adipocytes. Nonphosphorylated AS160 binds to GLUT4 vesicles and inhibits GLUT4 translocation, and AS160 phosphorylation overcomes this inhibitory effect. In the present study we detected several new functional features of AS160. The second phosphotyrosine-binding domain in AS160 encodes a phospholipid-binding domain that facilitates plasma membrane (PM) targeting of AS160, and this function is conserved in other related RabGAP/Tre-2/Bub2/Cdc16 (TBC) proteins and an AS160 ortholog in Drosophila. This region also contains a nonoverlapping intracellular GLUT4-containing storage vesicle (GSV) cargo-binding site. The interaction of AS160 with GSVs and not with the PM confers the inhibitory effect of AS160 on insulin-dependent GLUT4 translocation. Constitutive targeting of AS160 to the PM increased the surface GLUT4 levels, and this was attributed to both enhanced AS160 phosphorylation and 14-3-3 binding and inhibition of AS160 GAP activity. We propose a model wherein AS160 acts as a regulatory switch in the docking and/or fusion of GSVs with the PM. PMID:23045393

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

    PubMed

    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.

  12. 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

  13. 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

  14. Direct binding of the Kex2p cytosolic tail to the VHS domain of yeast Gga2p facilitates TGN to prevacuolar compartment transport and is regulated by phosphorylation

    PubMed Central

    De, Mithu; Abazeed, Mohamed E.; Fuller, Robert S.

    2013-01-01

    Human Golgi-localized, γ-ear–containing, ADP-ribosylation factor–binding proteins (Ggas) bind directly to acidic dileucine sorting motifs in the cytosolic tails (C-tails) of intracellular receptors. Despite evidence for a role in recruiting ubiquitinated cargo, it remains unclear whether yeast Ggas also function by binding peptide-sorting signals directly. Two-hybrid analysis shows that the Gga1p and Gga2p Vps27, Hrs, Stam (VHS) domains both bind a site in the Kex2p C-tail and that the Gga2p VHS domain binds a site in the Vps10p C-tail. Binding requires deletion of an apparently autoinhibitory sequence in the Gga2p hinge. Ser780 in the Kex2p C-tail is crucial for binding: an Ala substitution blocks but an Asp substitution permits binding. Biochemical assays using purified Gga2p VHS–GGA and TOM1 (GAT) and glutathione S-transferase–Kex2p C-tail fusions show that Gga2p binds directly to the Kex2p C-tail, with relative affinities Asp780 > Ser780 > Ala780. Affinity-purified antibody against a peptide containing phospho-Ser­780 recognizes wild-type Kex2p but not S780A Kex2p, showing that Ser780 is phosphorylated in vivo; phosphorylation of Ser780 is up-regulated by cell wall–damaging drugs. Finally, mutation of Ser780 alters trafficking of Kex2p both in vivo and in cell-free trans-Golgi network (TGN)–prevacuolar compartment (PVC) transport. Thus yeast Gga adaptors facilitate TGN–PVC transport by direct binding of noncanonical phosphoregulated Gga-binding sites in cargo molecules. PMID:23408788

  15. The double PHD finger domain of MOZ/MYST3 induces α-helical structure of the histone H3 tail to facilitate acetylation and methylation sampling and modification.

    PubMed

    Dreveny, Ingrid; Deeves, Sian E; Fulton, Joel; Yue, Baigong; Messmer, Marie; Bhattacharya, Amit; Collins, Hilary M; Heery, David M

    2014-01-01

    Histone tail modifications control many nuclear processes by dictating the dynamic exchange of regulatory proteins on chromatin. Here we report novel insights into histone H3 tail structure in complex with the double PHD finger (DPF) of the lysine acetyltransferase MOZ/MYST3/KAT6A. In addition to sampling H3 and H4 modification status, we show that the DPF cooperates with the MYST domain to promote H3K9 and H3K14 acetylation, although not if H3K4 is trimethylated. Four crystal structures of an extended DPF alone and in complex with unmodified or acetylated forms of the H3 tail reveal the molecular basis of crosstalk between H3K4me3 and H3K14ac. We show for the first time that MOZ DPF induces α-helical conformation of H3K4-T11, revealing a unique mode of H3 recognition. The helical structure facilitates sampling of H3K4 methylation status, and proffers H3K9 and other residues for modification. Additionally, we show that a conserved double glycine hinge flanking the H3 tail helix is required for a conformational change enabling docking of H3K14ac with the DPF. In summary, our data provide the first observations of extensive helical structure in a histone tail, revealing the inherent ability of the H3 tail to adopt alternate conformations in complex with chromatin regulators.

  16. The double PHD finger domain of MOZ/MYST3 induces α-helical structure of the histone H3 tail to facilitate acetylation and methylation sampling and modification

    PubMed Central

    Dreveny, Ingrid; Deeves, Sian E.; Fulton, Joel; Yue, Baigong; Messmer, Marie; Bhattacharya, Amit; Collins, Hilary M.; Heery, David M.

    2014-01-01

    Histone tail modifications control many nuclear processes by dictating the dynamic exchange of regulatory proteins on chromatin. Here we report novel insights into histone H3 tail structure in complex with the double PHD finger (DPF) of the lysine acetyltransferase MOZ/MYST3/KAT6A. In addition to sampling H3 and H4 modification status, we show that the DPF cooperates with the MYST domain to promote H3K9 and H3K14 acetylation, although not if H3K4 is trimethylated. Four crystal structures of an extended DPF alone and in complex with unmodified or acetylated forms of the H3 tail reveal the molecular basis of crosstalk between H3K4me3 and H3K14ac. We show for the first time that MOZ DPF induces α-helical conformation of H3K4-T11, revealing a unique mode of H3 recognition. The helical structure facilitates sampling of H3K4 methylation status, and proffers H3K9 and other residues for modification. Additionally, we show that a conserved double glycine hinge flanking the H3 tail helix is required for a conformational change enabling docking of H3K14ac with the DPF. In summary, our data provide the first observations of extensive helical structure in a histone tail, revealing the inherent ability of the H3 tail to adopt alternate conformations in complex with chromatin regulators. PMID:24150941

  17. Humanized-single domain antibodies (VH/VHH) that bound specifically to Naja kaouthia phospholipase A2 and neutralized the enzymatic activity.

    PubMed

    Chavanayarn, Charnwit; Thanongsaksrikul, Jeeraphong; Thueng-In, Kanyarat; Bangphoomi, Kunan; Sookrung, Nitat; Chaicumpa, Wanpen

    2012-07-01

    Naja kaouthia (monocled cobra) venom contains many isoforms of secreted phospholipase A2 (sPLA(2)). The PLA(2) exerts several pharmacologic and toxic effects in the snake bitten subject, dependent or independent on the enzymatic activity. N. kaouthia venom appeared in two protein profiles, P3 and P5, after fractionating the venom by ion exchange column chromatography. In this study, phage clones displaying humanized-camel single domain antibodies (VH/V(H)H) that bound specifically to the P3 and P5 were selected from a humanized-camel VH/V(H)H phage display library. Two phagemid transfected E. coli clones (P3-1 and P3-3) produced humanized-V(H)H, while another clone (P3-7) produced humanized-VH. At the optimal venom:antibody ratio, the VH/V(H)H purified from the E. coli homogenates neutralized PLA(2) enzyme activity comparable to the horse immune serum against the N. kaouthia holo-venom. Homology modeling and molecular docking revealed that the VH/V(H)H covered the areas around the PLA(2) catalytic groove and inserted their Complementarity Determining Regions (CDRs) into the enzymatic cleft. It is envisaged that the VH/V(H)H would ameliorate/abrogate the principal toxicity of the venom PLA(2) (membrane phospholipid catabolism leading to cellular and subcellular membrane damage which consequently causes hemolysis, hemorrhage, and dermo-/myo-necrosis), if they were used for passive immunotherapy of the cobra bitten victim. The speculation needs further investigations.

  18. An anti-phospholipase A2 receptor quantitative immunoassay and epitope analysis in membranous nephropathy reveals different antigenic domains of the receptor.

    PubMed

    Behnert, Astrid; Fritzler, Marvin J; Teng, Beina; Zhang, Meifeng; Bollig, Frank; Haller, Hermann; Skoberne, Andrej; Mahler, Michael; Schiffer, Mario

    2013-01-01

    The phospholipase A2 receptor (PLA2R) was recently discovered as a target autoantigen in patients with idiopathic membranous nephropathy (IMN). Published evidence suggests that the autoantibodies directed towards a conformation dependent epitope are currently effectively detected by a cell based assay (CBA) utilizing indirect immunofluorescence (IIF) on tissue culture cells transfected with the PLA2R cDNA. Limitations of such IIF-CBA assays include observer dependent subjective evaluation of semi-quantitative test results and the protocols are not amenable to high throughput diagnostic testing. We developed a quantitative, observer independent, high throughput capture immunoassay for detecting PLA2R autoantibodies on an addressable laser bead immunoassay (ALBIA) platform. Since reactive domains of PLA2R (i.e. epitopes) could be used to improve diagnostic tests by using small peptides in various high throughput diagnostic platforms, we identified PLA2R epitopes that bound autoantibodies of IMN patients. These studies confirmed that inter-molecular epitope spreading occurs in IMN but use of the cognate synthetic peptides in immunoassays was unable to conclusively distinguish between IMN patients and normal controls. However, combinations of these peptides were able to effectively absorb anti-PLA2R reactivity in IIF-CBA and an immunoassay that employed a lysate derived from HEK cells tranfected with and overexpressing PLA2R. While we provide evidence of intermolecular epitope spreading, our data indicates that in addition to conformational epitopes, human anti-PLA2R reactivity in a commercially available CBA and an addressable laser bead immunoassay is significantly absorbed by peptides representing epitopes of PLA2R.

  19. Humanized-single domain antibodies (VH/VHH) that bound specifically to Naja kaouthia phospholipase A2 and neutralized the enzymatic activity.

    PubMed

    Chavanayarn, Charnwit; Thanongsaksrikul, Jeeraphong; Thueng-In, Kanyarat; Bangphoomi, Kunan; Sookrung, Nitat; Chaicumpa, Wanpen

    2012-07-01

    Naja kaouthia (monocled cobra) venom contains many isoforms of secreted phospholipase A2 (sPLA(2)). The PLA(2) exerts several pharmacologic and toxic effects in the snake bitten subject, dependent or independent on the enzymatic activity. N. kaouthia venom appeared in two protein profiles, P3 and P5, after fractionating the venom by ion exchange column chromatography. In this study, phage clones displaying humanized-camel single domain antibodies (VH/V(H)H) that bound specifically to the P3 and P5 were selected from a humanized-camel VH/V(H)H phage display library. Two phagemid transfected E. coli clones (P3-1 and P3-3) produced humanized-V(H)H, while another clone (P3-7) produced humanized-VH. At the optimal venom:antibody ratio, the VH/V(H)H purified from the E. coli homogenates neutralized PLA(2) enzyme activity comparable to the horse immune serum against the N. kaouthia holo-venom. Homology modeling and molecular docking revealed that the VH/V(H)H covered the areas around the PLA(2) catalytic groove and inserted their Complementarity Determining Regions (CDRs) into the enzymatic cleft. It is envisaged that the VH/V(H)H would ameliorate/abrogate the principal toxicity of the venom PLA(2) (membrane phospholipid catabolism leading to cellular and subcellular membrane damage which consequently causes hemolysis, hemorrhage, and dermo-/myo-necrosis), if they were used for passive immunotherapy of the cobra bitten victim. The speculation needs further investigations. PMID:22852068

  20. Finite difference time domain method for calculating the band structure of a 2D photonic crystal and simulating the lensing effect

    NASA Astrophysics Data System (ADS)

    Rafiee Dastjerdi, S.; Ghanaatshoar, M.

    2013-08-01

    A finite difference time domain method based on regular Yee's algorithm in an orthogonal coordinate system is utilized to calculate the band structure of a two-dimensional square-lattice photonic crystal comprising dielectric cylinders in air background and to simulate the image formation of mentioned structure incorporating the perfectly matched layer boundary condition. By analyzing the photonic band diagram of this system, we find that the frequency region of effective negative refraction exists in the second band in near-infrared domain. In this case, electromagnetic wave propagates with a negative phase velocity and the evanescent waves can be supported to perform higher image resolution.

  1. Amino acid sequences in the alpha 1 domain and not glycosylation are important in HLA-A2/beta 2-microglobulin association and cell surface expression.

    PubMed Central

    Santos-Aguado, J; Biro, P A; Fuhrmann, U; Strominger, J L; Barbosa, J A

    1987-01-01

    The role of the single carbohydrate moiety present on the HLA-A2 molecule was studied by introducing several amino acid substitutions (by site-directed mutagenesis of the HLA-A2 gene) in the consensus glycosylation sequence Asn-X-Ser. Two different amino acid substitutions of the asparagine residue at position 86 (glutamine and aspartic acid) resulted in the synthesis of ca. 39,000-molecular-weight nonglycosylated heavy chains that were detected in the cytoplasm but not on the surface of mouse L-cell transfectants. However, a low level of surface expression was detected following transfection of human (rhabdomyosarcoma) cells or mouse L cells containing human beta 2-microglobulin. The defect in surface expression was not due to the absence of the glycan moiety, since the substitution of a glycine for a serine at amino acid 88 did not have the same drastic effect in the presence of human beta 2-microglobulin. These and other data suggest that the asparagine residue may play a critical role in the conformation of the HLA heavy chain and its interaction with beta 2-microglobulin. Immunofluorescence microscopy following permeabilization of the transfectants demonstrated that the unglycosylated HLA heavy chains are sequestered in an unidentified cellular compartment that is different from the Golgi structure. Images PMID:3550437

  2. 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…

  3. 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

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

    PubMed

    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; Huacca, Maribel E F; Fernandes, Cleberson F; Calderon, Leonardo A; Zuliani, Juliana P; Pereira da Silva, Luiz H; Soares, Andreimar M; Stabeli, Rodrigo G; Fernandes, Carla F C

    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

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

    PubMed

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

    2016-06-01

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

  6. Domain Engineering

    NASA Astrophysics Data System (ADS)

    Bjørner, Dines

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

  7. 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.

  8. Phosphatidylinositol 4-phosphate 5-kinase α facilitates Toll-like receptor 4-mediated microglial inflammation through regulation of the Toll/interleukin-1 receptor domain-containing adaptor protein (TIRAP) location.

    PubMed

    Nguyen, Tu Thi Ngoc; Kim, Yong Min; Kim, T Doohun; Le, Oanh Thi Tu; Kim, Jae Jin; Kang, Ho Chul; Hasegawa, Hiroshi; Kanaho, Yasunori; Jou, Ilo; Lee, Sang Yoon

    2013-02-22

    Phosphatidylinositol (PI) 4,5-bisphosphate (PIP(2)), generated by PI 4-phosphate 5-kinase (PIP5K), regulates many critical cellular events. PIP(2) is also known to mediate plasma membrane localization of the Toll/IL-1 receptor domain-containing adaptor protein (TIRAP), required for the MyD88-dependent Toll-like receptor (TLR) 4 signaling pathway. Microglia are the primary immune competent cells in brain tissue, and TLR4 is important for microglial activation. However, a functional role for PIP5K and PIP(2) in TLR4-dependent microglial activation remains unclear. Here, we knocked down PIP5Kα, a PIP5K isoform, in a BV2 microglial cell line using stable expression of lentiviral shRNA constructs or siRNA transfection. PIP5Kα knockdown significantly suppressed induction of inflammatory mediators, including IL-6, IL-1β, and nitric oxide, by lipopolysaccharide. PIP5Kα knockdown also attenuated signaling events downstream of TLR4 activation, including p38 MAPK and JNK phosphorylation, NF-κB p65 nuclear translocation, and IκB-α degradation. Complementation of the PIP5Kα knockdown cells with wild type but not kinase-dead PIP5Kα effectively restored the LPS-mediated inflammatory response. We found that PIP5Kα and TIRAP colocalized at the cell surface and interacted with each other, whereas kinase-dead PIP5Kα rendered TIRAP soluble. Furthermore, in LPS-stimulated control cells, plasma membrane PIP(2) increased and subsequently declined, and TIRAP underwent bi-directional translocation between the membrane and cytosol, which temporally correlated with the changes in PIP(2). In contrast, PIP5Kα knockdown that reduced PIP(2) levels disrupted TIRAP membrane targeting by LPS. Together, our results suggest that PIP5Kα promotes TLR4-associated microglial inflammation by mediating PIP(2)-dependent recruitment of TIRAP to the plasma membrane.

  9. Plasminogen Substrate Recognition by the Streptokinase-Plasminogen Catalytic Complex Is Facilitated by Arg253, Lys256, and Lys257 in the Streptokinase β-Domain and Kringle 5 of the Substrate*

    PubMed Central

    Tharp, Anthony C.; Laha, Malabika; Panizzi, Peter; Thompson, Michael W.; Fuentes-Prior, Pablo; Bock, Paul E.

    2009-01-01

    Streptokinase (SK) conformationally activates the central zymogen of the fibrinolytic system, plasminogen (Pg). The SK·Pg* catalytic complex binds Pg as a specific substrate and cleaves it into plasmin (Pm), which binds SK to form the SK·Pm complex that propagates Pm generation. Catalytic complex formation is dependent on lysine-binding site (LBS) interactions between a Pg/Pm kringle and the SK COOH-terminal Lys414. Pg substrate recognition is also LBS-dependent, but the kringle and SK structural element(s) responsible have not been identified. SK mutants lacking Lys414 with Ala substitutions of charged residues in the SK β-domain 250-loop were evaluated in kinetic studies that resolved conformational and proteolytic Pg activation. Activation of [Lys]Pg and mini-Pg (containing only kringle 5 of Pg) by SK with Ala substitutions of Arg253, Lys256, and Lys257 showed decreases in the bimolecular rate constant for Pm generation, with nearly total inhibition for the SK Lys256/Lys257 double mutant. Binding of bovine Pg (BPg) to the SK·Pm complex containing fluorescently labeled Pm demonstrated LBS-dependent assembly of a SK·labeled Pm·BPg ternary complex, whereas BPg did not bind to the complex containing the SK Lys256/Lys257 mutant. BPg was activated by SK·Pm with a Km indistinguishable from the KD for BPg binding to form the ternary complex, whereas the SK Lys256/Lys257 mutant did not support BPg activation. We conclude that SK residues Arg253, Lys256, and Lys257 mediate Pg substrate recognition through kringle 5 of the [Lys]Pg and mini-Pg substrates. A molecular model of the SK·kringle 5 complex identifies the putative interactions involved in LBS-dependent Pg substrate recognition. PMID:19473980

  10. 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

    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

  11. 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

  12. The CD8 coreceptor interaction with the alpha 3 domain of HLA class I is critical to the differentiation of human cytotoxic T-lymphocytes specific for HLA-A2 and HLA-Cw4.

    PubMed

    Wesley, P K; Clayberger, C; Lyu, S C; Krensky, A M

    1993-03-01

    The CD8 coreceptor interacts with MHC class I molecules through an acidic loop in the MHC alpha 3 domain. Mutations in this region reduced binding between cells expressing mutant HLA molecules and CHO cells transfected with CD8 alpha chain, with mutations at residue 227 having the greatest effects. This study was undertaken to examine the role of the CD8-HLA interaction in the generation of primary and long-term CTLs. HLA-A*0201 genes (wild type or mutated at residue 227) were transfected into a cell line that lacked expression of HLA-A or B molecules but expressed HLA-Cw4. These cells were used as stimulators for PBLs from a normal donor. Cultures were tested for cytotoxicity at various times thereafter. Transfectants expressing the HLA-A*0201 mutant gene were poor stimulators of primary HLA-A2-specific CTLs. In long-term culture, HLA-Cw4-specific CTLs predominated, indicating that continuous expansion of allogeneic CTLs depends upon an efficient CD8-MHC class I interaction. PMID:8320133

  13. 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. "A Test of…

  14. A Facilitation Performance Aid.

    ERIC Educational Resources Information Center

    Chevalier, Roger

    1997-01-01

    Presents a guide, derived from the Situational Leadership model, which describes the process that should be used in facilitating a group discussion. The process includes preparation, assessment, diagnosis, prescription, development, reinforcement, and follow-up. Three figures depict the Situational Leadership model, the facilitation process, and…

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

    PubMed

    Jessup, Ryan K

    2009-01-01

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

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

    PubMed

    Jessup, Ryan K

    2009-01-01

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

  17. 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…

  18. 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…

  19. 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…

  20. Facilitating Cognitive Development.

    ERIC Educational Resources Information Center

    Schwebel, Milton

    1985-01-01

    Human cognition research is shifting away from the importance of IQ and is emphasizing the stimulation and acceleration of a child's mental development. The emerging field of instructional psychology is trying to facilitate cognitive development. Current experimental programs--a university-school project in Belgium and a family project in…

  1. Formation of Freirian Facilitators.

    ERIC Educational Resources Information Center

    Noble, Phyllis

    This paper is written for people who are already familiar with the philosophy and methodology of Paulo Freire's liberatory education and are interested in creating a formation program for adult education facilitators using his ideas. The author describes the paper as "a collection of thoughts, of things to consider," when organizing such a…

  2. 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…

  3. 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,…

  4. Facilitation as a teaching strategy : experiences of facilitators.

    PubMed

    Lekalakala-Mokgele, E

    2006-08-01

    Changes in nursing education involve the move from traditional teaching approaches that are teacher-centred to facilitation, a student centred approach. The student-centred approach is based on a philosophy of teaching and learning that puts the learner on centre-stage. The aim of this study was to identify the challenges of facilitators of learning using facilitation as a teaching method and recommend strategies for their (facilitators) development and support. A qualitative, explorative and contextual design was used. Four (4) universities in South Africa which utilize facilitation as a teaching/ learning process were identified and the facilitators were selected to be the sample of the study. The main question posed during in-depth group interviews was: How do you experience facilitation as a teaching/learning method?. Facilitators indicated different experiences and emotions when they first had to facilitate learning. All of them indicated that it was difficult to facilitate at the beginning as they were trained to lecture and that no format for facilitation was available. They experienced frustrations and anxieties as a result. The lack of knowledge of facilitation instilled fear in them. However they indicated that facilitation had many benefits for them and for the students. Amongst the ones mentioned were personal and professional growth. Challenges mentioned were the fear that they waste time and that they do not cover the content. It is therefore important that facilitation be included in the training of nurse educators. PMID:17131610

  5. Morphology and interaction between lipid domains

    PubMed Central

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

    2009-01-01

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

  6. GLIAL ANKYRINS FACILITATE PARANODAL AXOGLIAL JUNCTION ASSEMBLY

    PubMed Central

    Chang, Kae-Jiun; Zollinger, Daniel R.; Susuki, Keiichiro; Sherman, Diane L.; Makara, Michael A.; Brophy, Peter J.; Cooper, Edward C.; Bennett, Vann; Mohler, Peter J.; Rasband, Matthew N.

    2014-01-01

    Neuron-glia interactions establish functional membrane domains along myelinated axons. These include nodes of Ranvier, paranodal axoglial junctions, and juxtaparanodes. Paranodal junctions are the largest vertebrate junctional adhesion complex, are essential for rapid saltatory conduction, and contribute to assembly and maintenance of nodes. However, the molecular mechanisms underlying paranodal junction assembly are poorly understood. Ankyrins are cytoskeletal scaffolds traditionally associated with Na+ channel clustering in neurons and important for membrane domain establishment and maintenance in many cell types. Here, we show that ankyrinB, expressed by Schwann cells, and ankyrinG, expressed by oligodendrocytes, are highly enriched at the glial side of paranodal junctions where they interact with the essential glial junctional component neurofascin 155. Conditional knockout of ankyrins in oligodendrocytes disrupts paranodal junction assembly and delays nerve conduction during early development in mice. Thus, glial ankyrins function as major scaffolds that facilitate early and efficient paranodal junction assembly in the developing central nervous system. PMID:25362471

  7. Reality based scenarios facilitate knowledge network development.

    PubMed

    Manning, J; Broughton, V; McConnell, E A

    1995-03-01

    The challenge in nursing education is to create a learning environment that enables students to learn new knowledge, access previously acquired information from a variety of disciplines, and apply this newly constructed knowledge to the complex and constantly changing world of practice. Faculty at the University of South Australia, School of Nursing, City Campus describe the use of reality based scenarios to acquire domain-specific knowledge and develop well connected associative knowledge networks, both of which facilitate theory based practice and the student's transition to the role of registered nurse.

  8. Facilitating post traumatic growth

    PubMed Central

    Turner, de Sales; Cox, Helen

    2004-01-01

    Background Whilst negative responses to traumatic injury have been well documented in the literature, there is a small but growing body of work that identifies posttraumatic growth as a salient feature of this experience. We contribute to this discourse by reporting on the experiences of 13 individuals who were traumatically injured, had undergone extensive rehabilitation and were discharged from formal care. All participants were injured through involvement in a motor vehicle accident, with the exception of one, who was injured through falling off the roof of a house. Methods In this qualitative study, we used an audio-taped in-depth interview with each participant as the means of data collection. Interviews were transcribed verbatim and analysed thematically to determine the participants' unique perspectives on the experience of recovery from traumatic injury. In reporting the findings, all participants' were given a pseudonym to assure their anonymity. Results Most participants indicated that their involvement in a traumatic occurrence was a springboard for growth that enabled them to develop new perspectives on life and living. Conclusion There are a number of contributions that health providers may make to the recovery of individuals who have been traumatically injured to assist them to develop new views of vulnerability and strength, make changes in relationships, and facilitate philosophical, physical and spiritual growth. PMID:15248894

  9. Preferential up-regulation of G2/M phase-specific genes by overexpression of the hyperactive form of NtmybA2 lacking its negative regulation domain in tobacco BY-2 cells.

    PubMed

    Kato, Kiichi; Gális, Ivan; Suzuki, Shiori; Araki, Satoshi; Demura, Taku; Criqui, Marie-Claire; Potuschak, Thomas; Genschik, Pascal; Fukuda, Hiroo; Matsuoka, Ken; Ito, Masaki

    2009-04-01

    Many G2/M phase-specific genes in plants contain mitosis-specific activator (MSA) elements, which act as G2/M phase-specific enhancers and bind with R1R2R3-Myb transcription factors. Here, we examined the genome-wide effects of NtmybA2 overexpression, one of the R1R2R3-Myb transcription factors in tobacco (Nicotiana tabacum). We used a custom-made 16-K cDNA microarray for comparative transcriptome analysis of transgenic tobacco BY-2 cell lines that overexpress NtmybA2 or its truncated hyperactive form. The microarray was also used to determine the transcript profile during the cell cycle in synchronized cultures of BY-2 cells. Combined microarray data from transgenic lines and synchronized cells revealed that overexpression of the truncated hyperactive form of NtmybA2, but not its full-length form, preferentially up-regulated many G2/M phase-specific genes in BY-2 cells. We determined promoter sequences of several such up-regulated genes and showed that all contain MSA-like motifs in the proximal regions of their promoters. One of the up-regulated genes, NtE2C, encoding for cyclin-specific ubiquitin carrier proteins, contained a single functional MSA-like motif, which specifically controlled the expression of a reporter gene in the G2/M phase in BY-2 cells. Furthermore, a genomic footprint experiment showed that the MSA element in the NtE2C promoter interacted with nuclear proteins in vivo. Therefore, we propose that the transcription of many G2/M phase-specific genes in tobacco is positively regulated by NtmybA2, in most cases through direct binding to the MSA elements. PMID:19244455

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

    PubMed

    Jackman, Skyler L; Turecek, Josef; Belinsky, Justine E; Regehr, Wade G

    2016-01-01

    It has been known for more than 70 years that synaptic strength is dynamically regulated in a use-dependent manner. At synapses with a low initial release probability, closely spaced presynaptic action potentials can result in facilitation, a short-term form of enhancement in which each subsequent action potential evokes greater neurotransmitter release. Facilitation can enhance neurotransmitter release considerably and can profoundly influence information transfer across synapses, but the underlying mechanism remains a mystery. One proposed mechanism is that a specialized calcium sensor for facilitation transiently increases the probability of release, and this sensor 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 disputed. Here we show that synaptotagmin 7 (Syt7) is a calcium sensor that is required for facilitation at several central synapses. In Syt7-knockout mice, facilitation is eliminated even though the initial probability of release and the 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.

  11. 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

  12. The Essential Elements of Facilitation.

    ERIC Educational Resources Information Center

    Priest, Simon; Gass, Michael; Gillis, Lee

    Most organizations find it difficult to implement change, and only about 10 percent of learning from training and development experiences is actually applied in the workplace. This book advocates facilitation as a means of enhancing change and increasing productivity. Facilitation engages employees by enhancing the processes associated with their…

  13. 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…

  14. 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

  15. Protein domain architectures.

    PubMed

    Mulder, Nicola J

    2010-01-01

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

  16. Huntingtin facilitates polycomb repressive complex 2

    PubMed Central

    Seong, Ihn Sik; Woda, Juliana M.; Song, Ji-Joon; Lloret, Alejandro; Abeyrathne, Priyanka D.; Woo, Caroline J.; Gregory, Gillian; Lee, Jong-Min; Wheeler, Vanessa C.; Walz, Thomas; Kingston, Robert E.; Gusella, James F.; Conlon, Ronald A.; MacDonald, Marcy E.

    2010-01-01

    Huntington's disease (HD) is caused by expansion of the polymorphic polyglutamine segment in the huntingtin protein. Full-length huntingtin is thought to be a predominant HEAT repeat α-solenoid, implying a role as a facilitator of macromolecular complexes. Here we have investigated huntingtin's domain structure and potential intersection with epigenetic silencer polycomb repressive complex 2 (PRC2), suggested by shared embryonic deficiency phenotypes. Analysis of a set of full-length recombinant huntingtins, with different polyglutamine regions, demonstrated dramatic conformational flexibility, with an accessible hinge separating two large α-helical domains. Moreover, embryos lacking huntingtin exhibited impaired PRC2 regulation of Hox gene expression, trophoblast giant cell differentiation, paternal X chromosome inactivation and histone H3K27 tri-methylation, while full-length endogenous nuclear huntingtin in wild-type embryoid bodies (EBs) was associated with PRC2 subunits and was detected with trimethylated histone H3K27 at Hoxb9. Supporting a direct stimulatory role, full-length recombinant huntingtin significantly increased the histone H3K27 tri-methylase activity of reconstituted PRC2 in vitro, and structure–function analysis demonstrated that the polyglutamine region augmented full-length huntingtin PRC2 stimulation, both in HdhQ111 EBs and in vitro, with reconstituted PRC2. Knowledge of full-length huntingtin's α-helical organization and role as a facilitator of the multi-subunit PRC2 complex provides a novel starting point for studying PRC2 regulation, implicates this chromatin repressive complex in a neurodegenerative disorder and sets the stage for further study of huntingtin's molecular function and the impact of its modulatory polyglutamine region. PMID:19933700

  17. 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…

  18. 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.

  19. Concerted but Noncooperative Activation of Nucleotide and Actuator Domains of the Ca-ATPase Upon Calcium Binding

    SciTech Connect

    Chen, Baowei; Mahaney, James E.; Mayer, M. Uljana; Bigelow, Diana J.; Squier, Thomas C.

    2008-11-25

    Calcium-dependent domain movements of the nucleotide (N) and actuator (A) domains of the SERCA2a isoform of the Ca-ATPase were assessed using constructs containing engineered tetracysteine binding motifs, which were expressed in insect High-Five cells and subsequently labeled with the biarsenical fluorophore 4’,5’-bis(1,3,2-dithoarsolan-2-yl)fluorescein (FlAsH-EDT2). Maximum catalytic function is retained in microsomes isolated from High-Five cells and labeled with FlAsH-EDT2. Distance measurements using the nucleotide analog TNP-ATP, which acts as a fluorescence resonance energy transfer (FRET) acceptor from FlAsH, identify a 2.4 Å increase in the spatial separation between the N- and A-domains induced by high-affinity calcium binding; this structural change is comparable to that observed in crystal structures. No significant distance changes occur across the N-domain between FlAsH and TNP-ATP, indicating that calcium activation induces rigid body domain movements rather than intradomain conformational changes. Calcium-dependent decreases in the fluorescence of FlAsH bound respectively to either the N- or A-domains indicate coordinated and noncooperative domain movements, where both N- and A-domains domains display virtually identical calcium dependencies (i.e., Kd = 4.8 ± 0.4 μM). We suggest that occupancy of a single high-affinity calcium binding site induces the rearrangement of the A- and N-domains of the Ca-ATPase to form an intermediate state, which facilitates ATP utilization upon occupancy of the second high-affinity calcium site to enhance transport efficiency.

  20. High School Facilitators and Inhibitors.

    ERIC Educational Resources Information Center

    Gnagey, William J.

    1981-01-01

    Teachers in a small high school nominated students whose classroom behavior facilitates or inhibits (disrupts) the learning process. These two groups were compared on locus of control, Maslow motive hierarchies, attitudes toward crime prevention, and achievement. Results are discussed and suggestions for helping disruptive students are made. (SJL)

  1. Sign Facilitation in Word Recognition.

    ERIC Educational Resources Information Center

    Wauters, Loes N.; Knoors, Harry E. T.; Vervloed, Mathijs P. J.; Aarnoutse, Cor A. J.

    2001-01-01

    This study examined whether use of sign language would facilitate reading word recognition by 16 deaf children (6- to 1 years-old) in the Netherlands. Results indicated that if words were learned through speech, accompanied by the relevant sign, accuracy of word recognition was greater than if words were learned solely through speech. (Contains…

  2. Producing Gestures Facilitates Route Learning

    PubMed Central

    So, Wing Chee; Ching, Terence Han-Wei; Lim, Phoebe Elizabeth; Cheng, Xiaoqin; Ip, Kit Yee

    2014-01-01

    The present study investigates whether producing gestures would facilitate route learning in a navigation task and whether its facilitation effect is comparable to that of hand movements that leave physical visible traces. In two experiments, we focused on gestures produced without accompanying speech, i.e., co-thought gestures (e.g., an index finger traces the spatial sequence of a route in the air). Adult participants were asked to study routes shown in four diagrams, one at a time. Participants reproduced the routes (verbally in Experiment 1 and non-verbally in Experiment 2) without rehearsal or after rehearsal by mentally simulating the route, by drawing it, or by gesturing (either in the air or on paper). Participants who moved their hands (either in the form of gestures or drawing) recalled better than those who mentally simulated the routes and those who did not rehearse, suggesting that hand movements produced during rehearsal facilitate route learning. Interestingly, participants who gestured the routes in the air or on paper recalled better than those who drew them on paper in both experiments, suggesting that the facilitation effect of co-thought gesture holds for both verbal and nonverbal recall modalities. It is possibly because, co-thought gesture, as a kind of representational action, consolidates spatial sequence better than drawing and thus exerting more powerful influence on spatial representation. PMID:25426624

  3. Producing gestures facilitates route learning.

    PubMed

    So, Wing Chee; Ching, Terence Han-Wei; Lim, Phoebe Elizabeth; Cheng, Xiaoqin; Ip, Kit Yee

    2014-01-01

    The present study investigates whether producing gestures would facilitate route learning in a navigation task and whether its facilitation effect is comparable to that of hand movements that leave physical visible traces. In two experiments, we focused on gestures produced without accompanying speech, i.e., co-thought gestures (e.g., an index finger traces the spatial sequence of a route in the air). Adult participants were asked to study routes shown in four diagrams, one at a time. Participants reproduced the routes (verbally in Experiment 1 and non-verbally in Experiment 2) without rehearsal or after rehearsal by mentally simulating the route, by drawing it, or by gesturing (either in the air or on paper). Participants who moved their hands (either in the form of gestures or drawing) recalled better than those who mentally simulated the routes and those who did not rehearse, suggesting that hand movements produced during rehearsal facilitate route learning. Interestingly, participants who gestured the routes in the air or on paper recalled better than those who drew them on paper in both experiments, suggesting that the facilitation effect of co-thought gesture holds for both verbal and nonverbal recall modalities. It is possibly because, co-thought gesture, as a kind of representational action, consolidates spatial sequence better than drawing and thus exerting more powerful influence on spatial representation. PMID:25426624

  4. 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…

  5. 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 ...

  6. 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…

  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. Prolonged adenosine A1 receptor activation in hypoxia and pial vessel disruption focal cortical ischemia facilitates clathrin-mediated AMPA receptor endocytosis and long-lasting synaptic inhibition in rat hippocampal CA3-CA1 synapses: differential regulation of GluA2 and GluA1 subunits by p38 MAPK and JNK.

    PubMed

    Chen, Zhicheng; Xiong, Cherry; Pancyr, Cassandra; Stockwell, Jocelyn; Walz, Wolfgang; Cayabyab, Francisco S

    2014-07-16

    Activation of presynaptic adenosine A1 receptors (A1Rs) causes substantial synaptic depression during hypoxia/cerebral ischemia, but postsynaptic actions of A1Rs are less clear. We found that A1Rs and GluA2-containing AMPA receptors (AMPARs) form stable protein complexes from hippocampal brain homogenates and cultured hippocampal neurons from Sprague Dawley rats. In contrast, adenosine A2A receptors (A2ARs) did not coprecipitate or colocalize with GluA2-containing AMPARs. Prolonged stimulation of A1Rs with the agonist N(6)-cyclopentyladenosine (CPA) caused adenosine-induced persistent synaptic depression (APSD) in hippocampal brain slices, and APSD levels were blunted by inhibiting clathrin-mediated endocytosis of GluA2 subunits with the Tat-GluA2-3Y peptide. Using biotinylation and membrane fractionation assays, prolonged CPA incubation showed significant depletion of GluA2/GluA1 surface expression from hippocampal brain slices and cultured neurons. Tat-GluA2-3Y peptide or dynamin inhibitor Dynasore prevented CPA-induced GluA2/GluA1 internalization. Confocal imaging analysis confirmed that functional A1Rs, but not A2ARs, are required for clathrin-mediated AMPAR endocytosis in hippocampal neurons. Pharmacological inhibitors or shRNA knockdown of p38 MAPK and JNK prevented A1R-mediated internalization of GluA2 but not GluA1 subunits. Tat-GluA2-3Y peptide or A1R antagonist 8-cyclopentyl-1,3-dipropylxanthine also prevented hypoxia-mediated GluA2/GluA1 internalization. Finally, in a pial vessel disruption cortical stroke model, a unilateral cortical lesion compared with sham surgery reduced hippocampal GluA2, GluA1, and A1R surface expression and also caused synaptic depression in hippocampal slices that was consistent with AMPAR downregulation and decreased probability of transmitter release. Together, these results indicate a previously unknown mechanism for A1R-induced persistent synaptic depression involving clathrin-mediated GluA2 and GluA1 internalization that

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

    PubMed

    Cole, Stephanie Dirla; Schleif, Robert

    2012-05-01

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

  10. 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…

  11. Counterfactual Thinking Facilitates Behavioral Intentions

    PubMed Central

    Smallman, Rachel; Roese, Neal J.

    2009-01-01

    People often ponder what might have been, and these counterfactual inferences have been linked to behavior regulation. Counterfactuals may enhance performance by either a content-specific pathway (via shift in behavioral intentions) and/or a content-neutral pathway (via mindsets or motivation). Three experiments provided new specification of the content-specific pathway. A sequential priming paradigm revealed that counterfactual judgments facilitated RTs to complete behavioral intention judgments relative to control judgments and to a no-judgment baseline (Experiment 1). This facilitation effect was found only for intention judgments that matched the information content of the counterfactual (Experiment 2) and only for intention judgments as opposed to a different judgment that nevertheless focused on the same information content (Experiment 3). These findings clarify the content-specific pathway by which counterfactuals influence behavior. PMID:20161221

  12. How We Think and Talk about Facilitation

    ERIC Educational Resources Information Center

    Kato, Fumitoshi

    2010-01-01

    Over the past few years, the notion of "facilitation" has been increasingly gaining attention and acceptance in Japan, especially in the context of education and training. Today, Japanese educators think and talk about facilitation, even if it is not yet clear what facilitation is. Interestingly enough, the term "facilitation" does not exist in…

  13. 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.

  14. Advance care planning: identifying system-specific barriers and facilitators

    PubMed Central

    Hagen, N.A.; Howlett, J.; Sharma, N.C.; Biondo, P.; Holroyd-Leduc, J.; Fassbender, K.; Simon, J.

    2015-01-01

    Background Advance care planning (acp) is an important process in health care today. How to prospectively identify potential local barriers and facilitators to uptake of acp across a complex, multi-sector, publicly funded health care system and how to develop specific mitigating strategies have not been well characterized. Methods We surveyed a convenience sample of clinical and administrative health care opinion leaders across the province of Alberta to characterize system-specific barriers and facilitators to uptake of acp. The survey was based on published literature about the barriers to and facilitators of acp and on the Michie Theoretical Domains Framework. Results Of 88 surveys, 51 (58%) were returned. The survey identified system-specific barriers that could challenge uptake of acp. The factors were categorized into four main domains. Three examples of individual system-specific barriers were “insufficient public engagement and misunderstanding,” “conflict among different provincial health service initiatives,” and “lack of infrastructure.” Local system-specific barriers and facilitators were subsequently explored through a semi-structured informal discussion group involving key informants. The group identified approaches to mitigate specific barriers. Conclusions Uptake of acp is a priority for many health care systems, but bringing about change in multi-sector health care systems is complex. Identifying system-specific barriers and facilitators to the uptake of innovation are important elements of successful knowledge translation. We developed and successfully used a simple and inexpensive process to identify local system-specific barriers and enablers to uptake of acp, and to identify specific mitigating strategies. PMID:26300673

  15. Domains and Naive Theories

    PubMed Central

    Gelman, Susan A.; Noles, Nicholaus S.

    2013-01-01

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

  16. 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.

  17. Learning and Domain Adaptation

    NASA Astrophysics Data System (ADS)

    Mansour, Yishay

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

  18. 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.

  19. Visualizing domain wall and reverse domain superconductivity

    PubMed Central

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

    2014-01-01

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

  20. Positive Emotion Facilitates Audiovisual Binding

    PubMed Central

    Kitamura, Miho S.; Watanabe, Katsumi; Kitagawa, Norimichi

    2016-01-01

    It has been shown that positive emotions can facilitate integrative and associative information processing in cognitive functions. The present study examined whether emotions in observers can also enhance perceptual integrative processes. We tested 125 participants in total for revealing the effects of emotional states and traits in observers on the multisensory binding between auditory and visual signals. Participants in Experiment 1 observed two identical visual disks moving toward each other, coinciding, and moving away, presented with a brief sound. We found that for participants with lower depressive tendency, induced happy moods increased the width of the temporal binding window of the sound-induced bounce percept in the stream/bounce display, while no effect was found for the participants with higher depressive tendency. In contrast, no effect of mood was observed for a simple audiovisual simultaneity discrimination task in Experiment 2. These results provide the first empirical evidence of a dependency of multisensory binding upon emotional states and traits, revealing that positive emotions can facilitate the multisensory binding processes at a perceptual level. PMID:26834585

  1. The Facilitation of Curriculum Research Workshops in TAFE.

    ERIC Educational Resources Information Center

    Anderson, Tony; Jones, Neil

    The processes entailed in facilitating or leading workshops or seminars for researching the curriculum in Technical and Further Education (TAFE) were examined by using a modified Delphi process, which was followed by a 2-day workshop. Participants in the study were all experienced curriculum development specialists with knowledge of one or more of…

  2. 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…

  3. 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.

  4. 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…

  5. Tobacco use prevention and health facilitator effectiveness.

    PubMed

    Young, R L; Elder, J P; Green, M; de Moor, C; Wildey, M B

    1988-11-01

    Tobacco prevention programs often use peers to teach refusal skills to other adolescents. College undergraduate health facilitators delivered a tobacco prevention intervention to sixth and seventh grade students in six schools. Outside observers evaluated facilitators in seven categories: being prepared, maintaining class control, keeping students' attention, encouraging participation, communication, relating to students, and working well in a team. Facilitators were rated highly in all categories. Higher rated health facilitators had more effect in reducing tobacco use than poorly rated facilitators. Facilitators who worked well in a team, related well to students, and were well-prepared were especially effective in positively influencing program outcomes.

  6. 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.…

  7. Guanidinium Pairing Facilitates Membrane Translocation.

    PubMed

    Allolio, Christoph; Baxova, Katarina; Vazdar, Mario; Jungwirth, Pavel

    2016-01-14

    Ab initio free energy calculations of guanidinium pairing in aqueous solution confirm the counterintuitive conjecture that the like-charge ion pair is thermodynamically stable. Transferring the guanidinium pair to the inside of a POPC lipid bilayer, like-charge ion pairing is found to occur also inside the membrane defect. It is found to contribute to the nonadditivity of ion transfer, thereby facilitating the presence of ions inside the bilayer. The effect is quantified by free energy decomposition and comparison with ammonium ions, which do not form a stable pair. The presence of two charges inside the center of the bilayer leads to the formation of a pore. Potential consequences for cell penetrating peptides and ion conduction are drawn.

  8. 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.

  9. 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…

  10. An experimental analysis of facilitated communication.

    PubMed Central

    Montee, B B; Miltenberger, R G; Wittrock, D; Watkins, N; Rheinberger, A; Stackhaus, J

    1995-01-01

    We evaluated the authorship of messages produced through facilitated communication by 7 adults with moderate or severe mental retardation and their facilitators. The clients had been reported to be communicating fluently through facilitated communication. We controlled the facilitators' access to information to be communicated in two evaluation formats, naming pictures and describing activities. In both formats we conducted three conditions: (a) the facilitator and client had access to the same information, (b) the facilitator did not have access to the picture or activity, and (c) the facilitator was given false information about the picture or activity. The results showed that the clients typed the correct answer only when the facilitator had access to the same information, never typed the correct answer when the facilitator had no information or false information, and typed the picture or activity presented to the facilitator when it was different from the one experienced by the client. These results provide unequivocal evidence for facilitator control of typing during facilitated communication. PMID:7601804

  11. 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)

  12. 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…

  13. 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;…

  14. 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

  15. An experimental assessment of facilitated communication.

    PubMed

    Wheeler, D L; Jacobson, J W; Paglieri, R A; Schwartz, A A

    1993-02-01

    This report presents a quantitative study of facilitated communication. Participants were 12 people living at an institutional autism program and 9 people who provided them with facilitated communication support. These subjects were the 12 most competent producers of facilitated communication in the program. They were shown pictures of familiar objects and asked to type the names of the objects under three conditions: (a) assisted typing with facilitators unaware of the content of the stimulus picture, (b) unassisted typing, and (c) a condition in which the participants and facilitators were each shown pictures at the same time. In this last condition the paired pictures were either the same or different, and the participant's typing was facilitated to label or describe the picture. These participants were unable to succeed in the tasks without facilitator assistance. On trials when the facilitators and participants had different pictures, the only "correct" labels were for pictures shown to the facilitators and not shown to the participants. This finding demonstrates that the facilitators were unknowingly determining what was typed.

  16. 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.

  17. 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…

  18. Just how versatile are domains?

    PubMed Central

    2008-01-01

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

  19. 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.

  20. 50 CFR 17.107 - Facilitating enforcement.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... WILDLIFE AND PLANTS (CONTINUED) ENDANGERED AND THREATENED WILDLIFE AND PLANTS (CONTINUED) Manatee Protection Areas § 17.107 Facilitating enforcement. Water vehicles operating in manatee sanctuary or...

  1. 50 CFR 17.107 - Facilitating enforcement.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... WILDLIFE AND PLANTS (CONTINUED) ENDANGERED AND THREATENED WILDLIFE AND PLANTS (CONTINUED) Manatee Protection Areas § 17.107 Facilitating enforcement. Water vehicles operating in manatee sanctuary or...

  2. 50 CFR 17.107 - Facilitating enforcement.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... WILDLIFE AND PLANTS (CONTINUED) ENDANGERED AND THREATENED WILDLIFE AND PLANTS (CONTINUED) Manatee Protection Areas § 17.107 Facilitating enforcement. Water vehicles operating in manatee sanctuary or...

  3. 50 CFR 17.107 - Facilitating enforcement.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... WILDLIFE AND PLANTS (CONTINUED) ENDANGERED AND THREATENED WILDLIFE AND PLANTS (CONTINUED) Manatee Protection Areas § 17.107 Facilitating enforcement. Water vehicles operating in manatee sanctuary or...

  4. 50 CFR 17.107 - Facilitating enforcement.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... WILDLIFE AND PLANTS (CONTINUED) ENDANGERED AND THREATENED WILDLIFE AND PLANTS (CONTINUED) Manatee Protection Areas § 17.107 Facilitating enforcement. Water vehicles operating in manatee sanctuary or...

  5. 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.

  6. Using learning theory, interprofessional facilitation competencies, and behavioral indicators to evaluate facilitator training.

    PubMed

    LeGros, Theresa A; Amerongen, Helen M; Cooley, Janet H; Schloss, Ernest P

    2015-01-01

    Despite the increasing need for faculty and preceptors skilled in interprofessional facilitation (IPF), the relative novelty of the field poses a challenge to the development and evaluation of IPF programs. We use learning theory and IPF competencies with associated behavioral indicators to develop and evaluate six key messages in IPF training and experience. Our mixed methods approach included two phases: quantitative data collection with embedded qualitative data, followed by qualitative data collection in explanatory sequential fashion. This enabled triangulated analyses of both data types and of facilitation behaviors from facilitator and student perspectives. Results indicate the competency-based training was effective. Facilitators felt comfortable performing behaviors associated with IPF competencies; student observations of those behaviors supported facilitator self-reported performance. Overall, students perceived more facilitation opportunities than facilitators. Findings corroborate the importance of recruiting seasoned facilitators and establishing IPF guidelines that acknowledge variable team dynamics and help facilitators recognize teachable moments. PMID:26230378

  7. Using learning theory, interprofessional facilitation competencies, and behavioral indicators to evaluate facilitator training.

    PubMed

    LeGros, Theresa A; Amerongen, Helen M; Cooley, Janet H; Schloss, Ernest P

    2015-01-01

    Despite the increasing need for faculty and preceptors skilled in interprofessional facilitation (IPF), the relative novelty of the field poses a challenge to the development and evaluation of IPF programs. We use learning theory and IPF competencies with associated behavioral indicators to develop and evaluate six key messages in IPF training and experience. Our mixed methods approach included two phases: quantitative data collection with embedded qualitative data, followed by qualitative data collection in explanatory sequential fashion. This enabled triangulated analyses of both data types and of facilitation behaviors from facilitator and student perspectives. Results indicate the competency-based training was effective. Facilitators felt comfortable performing behaviors associated with IPF competencies; student observations of those behaviors supported facilitator self-reported performance. Overall, students perceived more facilitation opportunities than facilitators. Findings corroborate the importance of recruiting seasoned facilitators and establishing IPF guidelines that acknowledge variable team dynamics and help facilitators recognize teachable moments.

  8. 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.

  9. Cellulose binding domain proteins

    DOEpatents

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

    1998-01-01

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

  10. THE AAA3 DOMAIN OF CYTOPLASMIC DYNEIN ACTS AS A SWITCH TO FACILITATE MICROTUBULE RELEASE

    PubMed Central

    Dewitt, Mark A.; Cypranowska, Caroline A.; Cleary, Frank B.; Belyy, Vladislav; Yildiz, Ahmet

    2014-01-01

    Cytoplasmic dynein is an AAA+ motor responsible for intracellular cargo transport and force generation along microtubules (MTs). Unlike kinesin and myosin, dynein contains multiple ATPase subunits, with AAA1 serving as the primary catalytic site. ATPase activity at AAA3 is also essential for robust motility, but its role in dynein’s mechanochemical cycle remains unclear. Here, we introduced transient pauses in Saccharomyces cerevisiae dynein motility by using a slowly hydrolyzing ATP analog. Analysis of pausing behavior revealed that AAA3 hydrolyzes nucleotide an order of magnitude slower than AAA1 and the two sites do not coordinate. ATPase mutations to AAA3 abolish the ability of dynein to modulate MT release. Nucleotide hydrolysis at AAA3 lifts this “MT gate” to fast motility. These results suggest that AAA3 acts as a switch that repurposes cytoplasmic dynein for fast cargo transport and MT anchoring tasks in cells. PMID:25486306

  11. "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…

  12. Peervention: Training Peer Facilitators for Prevention Education.

    ERIC Educational Resources Information Center

    Myrick, Robert D.; Folk, Betsy E.

    This book introduces students to the helping relationship and appropriate methods of responding to others through a variety of experiential training activities. The first chapter discusses the need for peer facilitators. The peer facilitator movement is traced to the 1970s, and the power of peer relationships is described. Four basic helping roles…

  13. Parent Involvement Facilitators: Unlocking Social Capital Wealth

    ERIC Educational Resources Information Center

    Ferrara, Margaret M.

    2015-01-01

    This case study provides an overview of a family outreach intervention that supports student retention in school through a school-home communication link. This intervention structure, which employs staff appropriately called parent involvement facilitators (PIFs), is one that school districts have employed to facilitate family engagement in…

  14. 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…

  15. A Model of Small Group Facilitator Competencies

    ERIC Educational Resources Information Center

    Kolb, Judith A.; Jin, Sungmi; Song, Ji Hoon

    2008-01-01

    This study used small group theory, quantitative and qualitative data collected from experienced practicing facilitators at three points of time, and a building block process of collection, analysis, further collection, and consolidation to develop a model of small group facilitator competencies. The proposed model has five components:…

  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. 75 FR 64641 - Facilitating Shareholder Director Nominations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-20

    ... COMMISSION 17 CFR Parts 200, 232, 240, and 249 RIN 3235-AK27 Facilitating Shareholder Director Nominations... rules that the Commission adopted to facilitate the effective exercise of shareholders' traditional state law rights to nominate and elect directors to company boards of directors. We are publishing...

  18. Escaping Homelessness: Anticipated and Perceived Facilitators

    ERIC Educational Resources Information Center

    Patterson, Allisha; Tweed, Roger

    2009-01-01

    One study with two distinct sections was conducted to identify factors facilitating escape from homelessness. In Section 1, 58 homeless individuals rated possible facilitators of escape (factors they believed would help them become more independent and self-sufficient). In Section 2, 80 participants who had already exited homelessness rated the…

  19. A Multitask Controlled Evaluation of Facilitated Communication.

    ERIC Educational Resources Information Center

    Vazquez, Carol A.

    1994-01-01

    This study tested the validity of facilitated communication with 2 students (ages 10 and 12) with autism, using a picture identification task, video task, and object identification. Subjects were able to report information unknown to the facilitator in one out of four controlled sessions. Strong evidence for direct cuing between subject and…

  20. Facilitator's Manual: Summer Transitions. Fifth Edition.

    ERIC Educational Resources Information Center

    Kuenzli, Linda A., Ed.

    A facilitator's manual for the Summer Transition Enrichment Program at Bowling Green State University is presented. The overall objectives of the program are: (1) to facilitate the transition of entering freshmen into the academic and cultural life of the university; and (2) to assist students in their personal growth and adjustment to the…

  1. 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)

  2. 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…

  3. Reconceptualizing the Pedagogical Value of Student Facilitation

    ERIC Educational Resources Information Center

    Oztok, Murat

    2016-01-01

    Sustained discourse is critical to the learning potential of online courses. And, while research has surfaced many factors that mediate interaction, it further suggests that sustained interaction remains elusive. In this paper, I propose that student facilitation may have an impact on the quality of facilitators' interactions following a week of…

  4. 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…

  5. Social Facilitation: A Test of Two Theories.

    ERIC Educational Resources Information Center

    Ryujin, Donald H.; And Others

    Social facilitation can be defined as the effect of an audience or coactors on performance. Research on social facilitation effects has produced some contradictory and confusing findings. Some studies have found that the presence of others enhances performance; other studies have found that the presence of an audience or coactors impairs…

  6. 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…

  7. 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.…

  8. Vitamin E facilitates the inactivation of the kinase Akt by the phosphatase PHLPP1.

    PubMed

    Huang, Po-Hsien; Chuang, Hsiao-Ching; Chou, Chih-Chien; Wang, Huiling; Lee, Su-Lin; Yang, Hsiao-Ching; Chiu, Hao-Chieh; Kapuriya, Naval; Wang, Dasheng; Kulp, Samuel K; Chen, Ching-Shih

    2013-03-19

    Vitamin E is a fat-soluble vitamin with antioxidant properties. Tocopherols are the predominant form of vitamin E found in the diet and in supplements and have garnered interest for their potential cancer therapeutic and preventive effects, such as the dephosphorylation of Akt, a serine/threonine kinase with a pivotal role in cell growth, survival, and metabolism. Dephosphorylation of Akt at Ser473 substantially reduces its catalytic activity and inhibits downstream signaling. We found that the mechanism by which α-tocopherol and γ-tocopherol facilitate this site-specific dephosphorylation of Akt was mediated through the pleckstrin homology (PH) domain-dependent recruitment of Akt and PHLPP1 (PH domain leucine-rich repeat protein phosphatase, isoform 1) to the plasma membrane. We structurally optimized these tocopherols to obtain derivatives with greater in vitro potency and in vivo tumor-suppressive activity in two prostate xenograft tumor models. Binding affinities for the PH domains of Akt and PHLPP1 were greater than for other PH domain-containing proteins, which may underlie the preferential recruitment of these proteins to membranes containing tocopherols. Molecular modeling revealed the structural determinants of the interaction with the PH domain of Akt that may inform strategies for continued structural optimization. By describing a mechanism by which tocopherols facilitate the dephosphorylation of Akt at Ser473, we provide insights into the mode of antitumor action of tocopherols and a rationale for the translational development of tocopherols into novel PH domain-targeted Akt inhibitors.

  9. Dissecting a locus control region: facilitation of enhancer function by extended enhancer-flanking sequences.

    PubMed Central

    Aronow, B J; Ebert, C A; Valerius, M T; Potter, S S; Wiginton, D A; Witte, D P; Hutton, J J

    1995-01-01

    Using transgenic mice, we have defined novel gene regulatory elements, termed "facilitators." These elements bilaterally flank, by up to 1 kb, a 200-bp T-cell-specific enhancer domain in the human adenosine deaminase (ADA) gene. Facilitators were essential for gene copy-proportional and integration site-independent reporter expression in transgenic thymocytes, but they had no effect on the enhancer in transfected T cells. Both segments were required. Individual segments had no activity. A lack of facilitator function caused positional susceptibility and prevented DNase I-hypersensitive site formation at the enhancer. The segments were required to be at opposed ends of the enhancer, and they could not be grouped together. Reversing the orientation of a facilitator segment caused a partial loss of function, suggesting involvement of a stereospecific chromatin structure. trans-acting factor access to enhancer elements was modeled by exposing nuclei to a restriction endonuclease. The enhancer domain was accessible to the 4-cutter DpnII in a tissue- and cell-type-specific fashion. However, unlike DNase I hypersensitivity and gene expression, accessibility to the endonuclease could occur without the facilitator segments, suggesting that an accessible chromatin domain is an intermediate state in the activational pathway. These results suggest that facilitators (i) are distinct from yet positionally constrained to the enhancer, (ii) participate in a chromatin structure transition that is necessary for the DNase I hypersensitivity and the transcriptional activating function of the enhancer, and (iii) act after cell-type-specific accessibility to the enhancer sequences is established by factors that do not require the facilitators to be present. PMID:7823928

  10. 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.

  11. 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

  12. Further insight into BRUTUS domain composition and functionality

    PubMed Central

    Matthiadis, Anna; Long, Terri A.

    2016-01-01

    ABSTRACT BRUTUS (BTS) is a hemerythrin (HHE) domain containing E3 ligase that facilitates the degradation of POPEYE-like (PYEL) proteins in a proteasomal-dependent manner. Deletion of BTS HHE domains enhances BTS stability in the presence of iron and also complements loss of BTS function, suggesting that the HHE domains are critical for protein stability but not for enzymatic function. The RING E3 domain plays an essential role in BTS' capacity to both interact with PYEL proteins and to act as an E3 ligase. Here we show that removal of the RING domain does not complement loss of BTS function. We conclude that enzymatic activity of BTS via the RING domain is essential for response to iron deficiency in plants. Further, we analyze possible BTS domain structure evolution and predict that the combination of domains found in BTS is specific to photosynthetic organisms, potentially indicative of a role for BTS and its orthologs in mitigating the iron-related challenges presented by photosynthesis. PMID:27359166

  13. Further insight into BRUTUS domain composition and functionality.

    PubMed

    Matthiadis, Anna; Long, Terri A

    2016-08-01

    BRUTUS (BTS) is a hemerythrin (HHE) domain containing E3 ligase that facilitates the degradation of POPEYE-like (PYEL) proteins in a proteasomal-dependent manner. Deletion of BTS HHE domains enhances BTS stability in the presence of iron and also complements loss of BTS function, suggesting that the HHE domains are critical for protein stability but not for enzymatic function. The RING E3 domain plays an essential role in BTS' capacity to both interact with PYEL proteins and to act as an E3 ligase. Here we show that removal of the RING domain does not complement loss of BTS function. We conclude that enzymatic activity of BTS via the RING domain is essential for response to iron deficiency in plants. Further, we analyze possible BTS domain structure evolution and predict that the combination of domains found in BTS is specific to photosynthetic organisms, potentially indicative of a role for BTS and its orthologs in mitigating the iron-related challenges presented by photosynthesis. PMID:27359166

  14. REvolver: modeling sequence evolution under domain constraints.

    PubMed

    Koestler, Tina; von Haeseler, Arndt; Ebersberger, Ingo

    2012-09-01

    Simulating the change of protein sequences over time in a biologically realistic way is fundamental for a broad range of studies with a focus on evolution. It is, thus, problematic that typically simulators evolve individual sites of a sequence identically and independently. More realistic simulations are possible; however, they are often prohibited by limited knowledge concerning site-specific evolutionary constraints or functional dependencies between amino acids. As a consequence, a protein's functional and structural characteristics are rapidly lost in the course of simulated evolution. Here, we present REvolver (www.cibiv.at/software/revolver), a program that simulates protein sequence alteration such that evolutionarily stable sequence characteristics, like functional domains, are maintained. For this purpose, REvolver recruits profile hidden Markov models (pHMMs) for parameterizing site-specific models of sequence evolution in an automated fashion. pHMMs derived from alignments of homologous proteins or protein domains capture information regarding which sequence sites remained conserved over time and where in a sequence insertions or deletions are more likely to occur. Thus, they describe constraints on the evolutionary process acting on these sequences. To demonstrate the performance of REvolver as well as its applicability in large-scale simulation studies, we evolved the entire human proteome up to 1.5 expected substitutions per site. Simultaneously, we analyzed the preservation of Pfam and SMART domains in the simulated sequences over time. REvolver preserved 92% of the Pfam domains originally present in the human sequences. This value drops to 15% when traditional models of amino acid sequence evolution are used. Thus, REvolver represents a significant advance toward a realistic simulation of protein sequence evolution on a proteome-wide scale. Further, REvolver facilitates the simulation of a protein family with a user-defined domain architecture at

  15. ECOD: An Evolutionary Classification of Protein Domains

    PubMed Central

    Kinch, Lisa N.; Pei, Jimin; Shi, Shuoyong; Kim, Bong-Hyun; Grishin, Nick V.

    2014-01-01

    Understanding the evolution of a protein, including both close and distant relationships, often reveals insight into its structure and function. Fast and easy access to such up-to-date information facilitates research. We have developed a hierarchical evolutionary classification of all proteins with experimentally determined spatial structures, and presented it as an interactive and updatable online database. ECOD (Evolutionary Classification of protein Domains) is distinct from other structural classifications in that it groups domains primarily by evolutionary relationships (homology), rather than topology (or “fold”). This distinction highlights cases of homology between domains of differing topology to aid in understanding of protein structure evolution. ECOD uniquely emphasizes distantly related homologs that are difficult to detect, and thus catalogs the largest number of evolutionary links among structural domain classifications. Placing distant homologs together underscores the ancestral similarities of these proteins and draws attention to the most important regions of sequence and structure, as well as conserved functional sites. ECOD also recognizes closer sequence-based relationships between protein domains. Currently, approximately 100,000 protein structures are classified in ECOD into 9,000 sequence families clustered into close to 2,000 evolutionary groups. The classification is assisted by an automated pipeline that quickly and consistently classifies weekly releases of PDB structures and allows for continual updates. This synchronization with PDB uniquely distinguishes ECOD among all protein classifications. Finally, we present several case studies of homologous proteins not recorded in other classifications, illustrating the potential of how ECOD can be used to further biological and evolutionary studies. PMID:25474468

  16. 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.

  17. 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. PMID:12693194

  18. 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…

  19. PAT: an intelligent authoring tool for facilitating clinical trial design.

    PubMed

    Tagaris, Anastasios; Andronikou, Vassiliki; Karanastasis, Efstathios; Chondrogiannis, Efthymios; Tsirmpas, Charalambos; Varvarigou, Theodora; Koutsouris, Dimitris

    2014-01-01

    Great investments are made by both private and public funds and a wealth of research findings is published, the research and development pipeline phases quite low productivity and tremendous delays. In this paper, we present a novel authoring tool which has been designed and developed for facilitating study design. Its underlying models are based on a thorough analysis of existing clinical trial protocols (CTPs) and eligibility criteria (EC) published in clinicaltrials.gov by domain experts. Moreover, its integration with intelligent decision support services and mechanisms linking the study design process with healthcare patient data as well as its direct access to literature designate it as a powerful tool offering great support to researchers during clinical trial design.

  20. The perforin pore facilitates the delivery of cationic cargos.

    PubMed

    Stewart, Sarah E; Kondos, Stephanie C; Matthews, Antony Y; D'Angelo, Michael E; Dunstone, Michelle A; Whisstock, James C; Trapani, Joseph A; Bird, Phillip I

    2014-03-28

    Cytotoxic lymphocytes eliminate virally infected or neoplastic cells through the action of cytotoxic proteases (granzymes). The pore-forming protein perforin is essential for delivery of granzymes into the cytoplasm of target cells; however the mechanism of this delivery is incompletely understood. Perforin contains a membrane attack complex/perforin (MACPF) domain and oligomerizes to form an aqueous pore in the plasma membrane; therefore the simplest (and best supported) model suggests that granzymes passively diffuse through the perforin pore into the cytoplasm of the target cell. Here we demonstrate that perforin preferentially delivers cationic molecules while anionic and neutral cargoes are delivered inefficiently. Furthermore, another distantly related pore-forming MACPF protein, pleurotolysin (from the oyster mushroom), also favors the delivery of cationic molecules, and efficiently delivers human granzyme B. We propose that this facilitated diffusion is due to conserved features of oligomerized MACPF proteins, which may include an anionic lumen. PMID:24558045

  1. Towards sustainable decision-support system facilitating EBM.

    PubMed

    Stolba, Nevena; Nguyen, Tho Manh; Tjoa, A Min

    2007-01-01

    Due to the immense volumes of medical data, the architecture of the future healthcare decision support systems focus more on interoperability than on integration. With the raising need for the creation of unified knowledge base, the federated approach to distributed data warehouses (DWH) is getting increasing attention. In this paper, we explore the idea of a federation technology and its uses within the domain of health, particularly in the conceptualization of DWH federation as a sustainable, appropriate and legitimate solution. Further, we present a federated DWH model which enables the interoperability between heterogeneous and distributed medical IS, which includes a sense and response mechanism and facilitates evidence-based medicine in order to primarily support the physicians at the point of care. A real-world scenario illustrates a possible application field in the area of emergency and intensive care.

  2. Comparison of the domain and frequency domain state feedbacks

    SciTech Connect

    Zhang, S.Y.

    1986-01-01

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

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

    ERIC Educational Resources Information Center

    Kaniel, Shlomo

    2010-01-01

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

  4. 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.

  5. 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)

  6. 36 CFR 1194.5 - Equivalent facilitation.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... COMPLIANCE BOARD ELECTRONIC AND INFORMATION TECHNOLOGY ACCESSIBILITY STANDARDS General § 1194.5 Equivalent facilitation. Nothing in this part is intended to prevent the use of designs or technologies as alternatives...

  7. 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

  8. 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.

  9. Managing and facilitating innovation and nurse satisfaction.

    PubMed

    Weston, Marla J

    2009-01-01

    Behaviors and actions that foster innovation are complementary to those associated with managing and facilitating nurse satisfaction. These include creating an organizational climate that encourages the generation, sharing, and implementation of new ideas; managing with the skills to hire and retain competent and creative individuals; and establishing the infrastructure and processes to recognize and embed best and promising practices into the organization. The ability to innovate and to manage and facilitate nurse satisfaction is a necessary competency for organizational success. PMID:19893447

  10. Categorical facilitation with equally discriminable colors.

    PubMed

    Witzel, Christoph; Gegenfurtner, Karl R

    2015-01-01

    This study investigates the impact of language on color perception. By categorical facilitation, we refer to an aspect of categorical perception, in which the linguistic distinction between categories affects color discrimination beyond the low-level, sensory sensitivity to color differences. According to this idea, discrimination performance for colors that cross a category border should be better than for colors that belong to the same category when controlling for low-level sensitivity. We controlled for sensitivity by using colors that were equally discriminable according to empirically measured discrimination thresholds. To test for categorical facilitation, we measured response times and error rates in a speeded discrimination task for suprathreshold stimuli. Robust categorical facilitation occurred for five out of six categories with a group of inexperienced observers, namely for pink, orange, yellow, green, and purple. Categorical facilitation was robust against individual variations of categories or the laterality of target presentation. However, contradictory effects occurred in the blue category, most probably reflecting the difficulty to control effects of sensory mechanisms at the green-blue boundary. Moreover, a group of observers who were highly familiar with the discrimination task did not show consistent categorical facilitation in the other five categories. This trained group had much faster response times than the inexperienced group without any speed-accuracy trade-off. Additional analyses suggest that categorical facilitation occurs when observers pay attention to the categorical distinction but not when they respond automatically based on sensory feed-forward information. PMID:26129860

  11. 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.

  12. On Probability Domains III

    NASA Astrophysics Data System (ADS)

    Frič, Roman; Papčo, Martin

    2015-12-01

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

  13. Selective inactivation of adenosine A2A receptors in striatal neurons enhances working memory and reversal learning

    PubMed Central

    Wei, Catherine J.; Singer, Philipp; Coelho, Joana; Boison, Detlev; Feldon, Joram; Yee, Benjamin K.; Chen, Jiang-Fan

    2011-01-01

    The adenosine A2A receptor (A2AR) is highly enriched in the striatum where it is uniquely positioned to integrate dopaminergic, glutamatergic, and other signals to modulate cognition. Although previous studies support the hypothesis that A2AR inactivation can be pro-cognitive, analyses of A2AR's effects on cognitive functions have been restricted to a small subset of cognitive domains. Furthermore, the relative contribution of A2ARs in distinct brain regions remains largely unknown. Here, we studied the regulation of multiple memory processes by brain region-specific populations of A2ARs. Specifically, we evaluated the cognitive impacts of conditional A2AR deletion restricted to either the entire forebrain (i.e., cerebral cortex, hippocampus, and striatum, fb-A2AR KO) or to striatum alone (st-A2AR KO) in recognition memory, working memory, reference memory, and reversal learning. This comprehensive, comparative analysis showed for the first time that depletion of A2AR-dependent signaling in either the entire forebrain or striatum alone is associated with two specific phenotypes indicative of cognitive flexibility—enhanced working memory and enhanced reversal learning. These selective pro-cognitive phenotypes seemed largely attributed to inactivation of striatal A2ARs as they were captured by A2AR deletion restricted to striatal neurons. Neither spatial reference memory acquisition nor spatial recognition memory were grossly affected, and no evidence for compensatory changes in striatal or cortical D1, D2, or A1 receptor expression was found. This study provides the first direct demonstration that targeting striatal A2ARs may be an effective, novel strategy to facilitate cognitive flexibility under normal and pathologic conditions. PMID:21693634

  14. STAS Domain Structure and Function

    PubMed Central

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

    2011-01-01

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

  15. Rating knowledge sharing in cross-domain collaborative filtering.

    PubMed

    Li, Bin; Zhu, Xingquan; Li, Ruijiang; Zhang, Chengqi

    2015-05-01

    Cross-domain collaborative filtering (CF) aims to share common rating knowledge across multiple related CF domains to boost the CF performance. In this paper, we view CF domains as a 2-D site-time coordinate system, on which multiple related domains, such as similar recommender sites or successive time-slices, can share group-level rating patterns. We propose a unified framework for cross-domain CF over the site-time coordinate system by sharing group-level rating patterns and imposing user/item dependence across domains. A generative model, say ratings over site-time (ROST), which can generate and predict ratings for multiple related CF domains, is developed as the basic model for the framework. We further introduce cross-domain user/item dependence into ROST and extend it to two real-world cross-domain CF scenarios: 1) ROST (sites) for alleviating rating sparsity in the target domain, where multiple similar sites are viewed as related CF domains and some items in the target domain depend on their correspondences in the related ones; and 2) ROST (time) for modeling user-interest drift over time, where a series of time-slices are viewed as related CF domains and a user at current time-slice depends on herself in the previous time-slice. All these ROST models are instances of the proposed unified framework. The experimental results show that ROST (sites) can effectively alleviate the sparsity problem to improve rating prediction performance and ROST (time) can clearly track and visualize user-interest drift over time.

  16. DOUTfinder--identification of distant domain outliers using subsignificant sequence similarity.

    PubMed

    Novatchkova, Maria; Schneider, Georg; Fritz, Richard; Eisenhaber, Frank; Schleiffer, Alexander

    2006-07-01

    DOUTfinder is a web-based tool facilitating protein domain detection among related protein sequences in the twilight zone of sequence similarity. The sequence set required for this analysis can be provided by the user or will be collected using PSI-BLAST if a single sequence is given as an input. The obtained sequence family is analyzed for known Pfam and SMART domains, and the thereby identified subsignificant domain similarities are evaluated further. Domains with several subthreshold hits in the query set are ranked based on a sum-score function and likely homologous domains are suggested according to established cut-offs. By providing a post-filtering procedure for subsignificant domain hits DOUTfinder allows the detection of non-trivial domain relationships and can thereby lead to new insights into the function and evolution of distantly related sequence families. DOUTfinder is available at http://mendel.imp.ac.at/dout/.

  17. Facilitators and Challenges in Psychosocial Adaptation to Being at Increased Familial Risk of Breast Cancer.

    PubMed

    Heiniger, Louise; Price, Melanie A; Charles, Margaret; Butow, Phyllis N

    2015-12-01

    Little is known about the process of psychosocial adaptation to familial risk in tested and untested individuals at increased familial risk of cancer. This paper presents findings from a qualitative study of 36 women participating in the Kathleen Cuningham Consortium for Research into Familial Breast cancer (kConFab) Psychosocial study. Facilitators and challenges in psychosocial adaptation were identified through semi-structured interviews. The women, who were either tested (carriers or non-carriers of breast cancer susceptibility mutations) or untested (ineligible for testing or eligible but delayed or declined testing), described personal, support network and healthcare characteristics that impacted on the adaptation process. Challenges in one domain could be overcome by facilitators in other domains and key differences relating to whether women had undergone testing, or not, were identified. Tested and untested women with an increased familial risk of breast cancer may benefit from support tailored to their mutation testing status in order to enhance adaptation.

  18. Physically facilitating drug-delivery systems

    PubMed Central

    Rodriguez-Devora, Jorge I; Ambure, Sunny; Shi, Zhi-Dong; Yuan, Yuyu; Sun, Wei; Xu, Tao

    2012-01-01

    Facilitated/modulated drug-delivery systems have emerged as a possible solution for delivery of drugs of interest to pre-allocated sites at predetermined doses for predefined periods of time. Over the past decade, the use of different physical methods and mechanisms to mediate drug release and delivery has grown significantly. This emerging area of research has important implications for development of new therapeutic drugs for efficient treatments. This review aims to introduce and describe different modalities of physically facilitating drug-delivery systems that are currently in use for cancer and other diseases therapy. In particular, delivery methods based on ultrasound, electrical, magnetic and photo modulations are highlighted. Current uses and areas of improvement for these different physically facilitating drug-delivery systems are discussed. Furthermore, the main advantages and drawbacks of these technologies reviewed are compared. The review ends with a speculative viewpoint of how research is expected to evolve in the upcoming years. PMID:22485192

  19. Spectral Domain Phase Microscopy

    NASA Astrophysics Data System (ADS)

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

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

  20. 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

  1. 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

  2. Effects of Domain Knowledge, Working Memory Capacity, and Age on Cognitive Performance: An Investigation of the Knowledge-Is-Power Hypothesis

    ERIC Educational Resources Information Center

    Hambrick, David Z.; Engle, Randall W.

    2002-01-01

    Domain knowledge facilitates performance in many cognitive tasks. However, very little is known about the interplay between domain knowledge and factors that are believed to reflect general, and relatively stable, characteristics of the individual. The primary goal of this study was to investigate the interplay between domain knowledge and one…

  3. 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…

  4. 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…

  5. Grief Support Group Curriculum: Facilitator's Handbook.

    ERIC Educational Resources Information Center

    Lehmann, Linda; Jimerson, Shane R.; Gaasch, Ann

    This handbook is designed for facilitators of grief support groups for mourning children. The first chapter discusses the history, philosophy, and format of a specific curriculum - the Mourning Child curriculum. This curriculum, originally written in 1986 and later expanded and revised, has been used with hundreds of children. Chapter two covers…

  6. 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,…

  7. 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…

  8. Facilitating Engagement by Differentiating Independent Reading

    ERIC Educational Resources Information Center

    Kelley, Michelle J.; Clausen-Grace, Nicki

    2009-01-01

    The authors provide teachers with a rationale for engaging students in independent reading using a differentiated approach. By profiling types of readers, sharing observational tools, and offering teaching suggestions for each type of reader the authors give practical suggestions to facilitate reading engagement and make independent reading more…

  9. The Community Leisure Facilitator. Project REC.

    ERIC Educational Resources Information Center

    Moon, M. Sherril; And Others

    Developed as part of a project to integrate youth with disabilities into regular recreational and leisure activities, this report focuses on the role of the community leisure facilitator (CLF), defined as a professional, friend, family member, or volunteer who assists individuals with disabilities to enjoy the same leisure pursuits as other…

  10. 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…

  11. 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...

  12. Facilitating Sustainable Professional Development through Lesson Study

    ERIC Educational Resources Information Center

    Hunter, Jodie; Back, Jenni

    2011-01-01

    Developing sustainable professional development which facilitates teachers of mathematics to develop effective mathematics pedagogy has been a key aim in recent years. This paper examines how lesson study can be used with networks of teachers as a vehicle to promote and sustain professional development. Drawing on findings from a year-long study…

  13. 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…

  14. Facilitating Transfer through Student Support Services.

    ERIC Educational Resources Information Center

    Brawer, Florence B.

    Drawing on findings of two Center for the Study of Community College (CSCC) projects, this paper reviews some of the services offered by community colleges to facilitate transfer to four-year institutions. Introductory material provides background on the low rates of student transfer and on the CSCC projects, which involve 6 large urban community…

  15. 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...

  16. 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…

  17. 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…

  18. Utilizing the Internet to Facilitate Classroom Learning

    ERIC Educational Resources Information Center

    Tucker, Jan; Courts, Bari

    2010-01-01

    Traditional theories on classroom learning focus on fixed curriculum, static learning tools and believe learning is achieved through repetition and rote memorization. The instructor's role in a traditional learning environment focuses on providing direction to the student versus facilitating learning. As the technology age becomes more prevalent…

  19. 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…

  20. 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…

  1. 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…

  2. 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…

  3. Social Facilitation of Laughter in Children

    ERIC Educational Resources Information Center

    Chapman, Antony J.

    1973-01-01

    The present study is concerned primarily with demonstrating that laughter can be socially facilitated. It showed that children, presented aurally with laughter-provoking material, laugh more in the presence of a companion, whether or not the companion can hear the material. (Author/RK)

  4. Facilitating Learning Organizations. Making Learning Count.

    ERIC Educational Resources Information Center

    Marsick, Victoria J.; Watkins, Karen E.

    This book offers advice to facilitators and change agents who wish to build systems-level learning to create knowledge that can be used to gain a competitive advantage. Chapter 1 describes forces driving companies to build, sustain, and effectively use systems-level learning and presents and links a working definition of the learning organization…

  5. Facilitating Teaching and Learning across STEM Fields

    ERIC Educational Resources Information Center

    Ejiwale, James A.

    2012-01-01

    The reformation of the contents for instruction across STEM fields has changed the role of STEM educators from being a "dictator" in the classroom/laboratory to a facilitator of students' activities. More important, this new paradigm and professional orientation for STEM educators is no more limited to delivering instruction intuitively, but with…

  6. How Facilities Facilitate Education. Principal's Notebook.

    ERIC Educational Resources Information Center

    Quinn, Linda

    2001-01-01

    Advice on making facilities facilitate education includes: an educational vision comes first, involve all stakeholders, working smarter requires a systems approach, systems-focused planning takes time, partnerships stretch limited resources, "beautiful" is not expensive, change is tough, building a community is as important as building a facility,…

  7. 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…

  8. 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.…

  9. Career Planning for Minority Women. Facilitator's Manual.

    ERIC Educational Resources Information Center

    Jackson, Stanlie M., Ed.

    This facilitator's manual consists of guidelines and materials for use in conducting a workshop dealing with career planning for minority women. Covered in the first half of the manual are the following aspects of implementing the workshop: background on the need for and development of the workshop, a workshop outline and time schedule, the…

  10. Management Basics for Minority Women. Facilitator's Manual.

    ERIC Educational Resources Information Center

    Jackson, Stanlie M., Ed.

    This facilitator's manual consists of guidelines and materials for use in conducting a workshop dealing with three management basics for minority women--communication, decision making, and interpersonal skills. Covered in the first half of the manual are the following aspects of implementing the workshop: background on the need for and development…

  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. Microcomputers as Social Facilitators in Integrated Preschools.

    ERIC Educational Resources Information Center

    Spiegel-McGill, Phyllis; And Others

    1989-01-01

    The study compared the effects of different play conditions (microcomputer, remote-control robot, or no toys) on the amount of time four dyads of handicapped/nonhandicapped children would interact during structured play. Results suggested that microcomputers may serve as social facilitators for children with significant social and language…

  13. Social Facilitation as Self-Presentation.

    ERIC Educational Resources Information Center

    Bond, Charles F., Jr.

    Social facilitation as a self-presentational display, and social performance impairment attributable to perceived public failure, are examined in a study of context effects in verbal learning. Female undergraduates (N=72) served as subjects with one male who served as an "audience." Performance data indicate that, consistent with the present…

  14. 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 …

  15. The Facilitator. Technical Note No. 11.

    ERIC Educational Resources Information Center

    Barriga, Patricio; And Others

    This paper describes the concept, training, and experiences of community facilitators as change agents in a nonformal education project in rural Ecuador. Presently, the social, economic, and political context of the rural Ecuadorian consists of poverty, racial prejudice, economic exploitation, and psychological dependency. The project attempted to…

  16. 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…

  17. 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…

  18. Facilitating Reminiscence Groups: Perceptions of Group Leaders

    ERIC Educational Resources Information Center

    Christensen, Teresa M.; Hulse-Killacky, Diana; Salgado, Roy A.; Thornton, Mark D.; Miller, Jason L.

    2006-01-01

    This article presents the results of a two-year qualitative investigation in which group leaders provided their perceptions of the process of facilitating reminiscence groups with elderly persons in a residential care facility. Group Culture emerged as the dominant construct. Findings from this study can serve guide leaders who are interested in…

  19. 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.

  20. Dynamical domain wall and localization

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

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

  1. Memory facilitation educed by food intake.

    PubMed

    Oomura, Y; Sasaki, K; Li, A J

    1993-09-01

    Acidic fibroblast growth factor (aFGF) in rat CSF increased 1000 times in the 2-h period after food intake, or IP, or ICV glucose infusion. The ICV application of aFGF dose dependently depresses and anti-aFGF antibody facilitates food intake. aFGF is produced in the ependymal cells and released into the CSF in response to increased glucose in the CSF caused by food intake. Released aFGF diffused into the brain parenchyma and was taken up into neurons in the hypothalamus, hippocampus, amygdala, etc. IP injection of glucose 2 h before a task that combined acquisition with passive avoidance significantly increased retention of avoidance by mice tested 24 h later. In a Morris water maze task, IP glucose injection 2 h before a first trial block reduced time to find and climb onto a platform hidden just below the water surface. The glucose facilitation of these affective and spatial memory were abolished by pretreatment with anti-aFGF antibody applied ICV. Continuous ICV infusion of aFGF into rats also significantly increased the reliability of passive avoidance for several days. After food intake, centrally released aFGF reaches the hippocampus and facilitates memory; peripherally released cholecystokinin reaches the endings of the afferent vagal nerves in the portal vein and changes their activity, which modulates hippocampal activity, to lead to memory facilitation. This, however, is blocked by vagotomy below the diaphragm. The results indicate the importance of food intake, not only to maintain homeostasis, but also to prepare a readiness state for memory facilitation. PMID:7692459

  2. 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

  3. Vitamin E Facilitates the Inactivation of the Kinase Akt by the Phosphatase PHLPP1

    PubMed Central

    Huang, Po-Hsien; Chuang, Hsiao-Ching; Chou, Chih-Chien; Wang, Huiling; Lee, Su-Lin; Yang, Hsiao-Ching; Chiu, Hao-Chieh; Kapuriya, Naval; Wang, Dasheng; Kulp, Samuel K.; Chen, Ching-Shih

    2014-01-01

    Vitamin E is a fat-soluble vitamin that includes isomers of tocopherols and tocotrienols which are known for their antioxidant properties. Tocopherols are the predominant form encountered in the diet and through supplementation, and have garnered interest for their potential cancer therapeutic and chemopreventive effects, which include the dephosphorylation of Akt, a serine/threonine kinase that plays a pivotal role in important cellular processes, such as cell growth, survival, metabolism and motility. Full catalytic activation of Akt requires phosphorylation at both Thr308 and Ser473. Dephosphorylation of Ser473 drastically reduces Akt catalytic activity and the number of downstream substrates it can regulate. The mechanism by which α- and γ-tocopherol facilitate the selective dephosphorylation of the kinase Akt at Ser473 was investigated. We showed that this site-specific Akt dephosphorylation was mediated through the pleckstrin homology (PH) domain-dependent recruitment to the plasma membrane of Akt and PHLPP1 (PH domain leucine-rich repeat protein phosphatase, isoform 1), a phosphatase that dephosphorylates Akt at Ser473. The ability of α- and γ-tocopherol to induce PHLPP-mediated Akt inhibition established PHLPP as a “druggable” target. We structurally optimized these tocopherols to obtain derivatives with greater in vitro potency and in vivo tumor-suppressive activity in two prostate xenograft tumor models. Binding affinities for the PH domains of Akt and PHLPP1 were greater than for other PH domain-containing proteins, which may underlie the preferential membrane recruitment of these proteins. Molecular modeling revealed the structural determinants of the interaction with the PH domain of Akt that may inform strategies for continued structural optimization. These findings describe a mechanism by which tocopherols facilitate the dephosphorylation of Akt at Ser473, thereby providing insights into the mode of antitumor action of tocopherols and a

  4. 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

  5. On Probability Domains

    NASA Astrophysics Data System (ADS)

    Frič, Roman; Papčo, Martin

    2010-12-01

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

  6. Fractional diffusion on bounded domains

    SciTech Connect

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

    2015-03-13

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

  7. 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. PMID:10881768

  8. 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.

  9. How academic teachers perceive and facilitate creativity

    NASA Astrophysics Data System (ADS)

    Bjørner, Thomas; Busk Kofoed, Lise

    2013-10-01

    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 and how do they facilitate it? Many of the answers point to the pedagogical approach used in problem-based learning, which are perceived as an important element for the creative process. In this paper we will also argue the importance of including the social context (both at a macro and at a micro level) in the definition and use of creativity in engineering education.

  10. Generic language facilitates children's cross-classification

    PubMed Central

    Nguyen, Simone P.; Gelman, Susan 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 language. Experiment 1 showed that generics facilitate 5-year-olds' and adults' cross-classification when expressed at an appropriate level of generalization (e.g., “foods,” “birthday party things”), whereas Experiment 2 showed that such effects disappeared when labels were at an inappropriate level of generalization (e.g., “pizzas,” “balloons”). Experiments 3 and 4 offered additional controls. Taken together, the findings demonstrate that language can guide and direct children's multiple categorizations. PMID:22888182

  11. 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.

  12. Facilitating emergent change in a healthcare setting.

    PubMed

    Dickens, Peter M

    2013-01-01

    During my doctoral research, I identified new ways of thinking about complexity in organizations. This involved embracing the capacity of complex systems to find their own form of order and coherence, often referred to as self-organization, and then asking the question, "What can organizational leaders do to create the systems and structures that would facilitate emergent change?" Emergent change comes from within and through the active members of a system and not according to some external prompting or design. This results in the sort of change capacity that enables an organization to be agile and resilient through a high level of employee engagement. The question was answered by identifying and validating organizational-specific factors that facilitate emergent change.

  13. Isoform-selective Inhibition of Facilitative Glucose Transporters

    PubMed Central

    Hresko, Richard C.; Kraft, Thomas E.; Tzekov, Anatoly; Wildman, Scott A.; Hruz, Paul W.

    2014-01-01

    Pharmacologic HIV protease inhibitors (PIs) and structurally related oligopeptides are known to reversibly bind and inactivate the insulin-responsive facilitative glucose transporter 4 (GLUT4). Several PIs exhibit isoform selectivity with little effect on GLUT1. The ability to target individual GLUT isoforms in an acute and reversible manner provides novel means both to investigate the contribution of individual GLUTs to health and disease and to develop targeted treatment of glucose-dependent diseases. To determine the molecular basis of transport inhibition, a series of chimeric proteins containing transmembrane and cytosolic domains from GLUT1 and GLUT4 and/or point mutations were generated and expressed in HEK293 cells. Structural integrity was confirmed via measurement of N-[2-[2-[2-[(N-biotinylcaproylamino)ethoxy)ethoxyl]-4-[2-(trifluoromethyl)-3H-diazirin-3-yl]benzoyl]-1,3-bis(mannopyranosyl-4-yloxy)-2-propylamine (ATB-BMPA) labeling of the chimeric proteins in low density microsome fractions isolated from stably transfected 293 cells. Functional integrity was assessed via measurement of zero-trans 2-deoxyglucose (2-DOG) uptake. ATB-BMPA labeling studies and 2-DOG uptake revealed that transmembrane helices 1 and 5 contain amino acid residues that influence inhibitor access to the transporter binding domain. Substitution of Thr-30 and His-160 in GLUT1 to the corresponding positions in GLUT4 is sufficient to completely transform GLUT1 into GLUT4 with respect to indinavir inhibition of 2-DOG uptake and ATB-BMPA binding. These data provide a structural basis for the selectivity of PIs toward GLUT4 over GLUT1 that can be used in ongoing novel drug design. PMID:24706759

  14. To adapt or not to adapt: the question of domain-general cognitive control.

    PubMed

    Kan, Irene P; Teubner-Rhodes, Susan; Drummey, Anna B; Nutile, Lauren; Krupa, Lauren; Novick, Jared M

    2013-12-01

    What do perceptually bistable figures, sentences vulnerable to misinterpretation and the Stroop task have in common? Although seemingly disparate, they all contain elements of conflict or ambiguity. Consequently, in order to monitor a fluctuating percept, reinterpret sentence meaning, or say "blue" when the word RED is printed in blue ink, individuals must regulate attention and engage cognitive control. According to the Conflict Monitoring Theory (Botvinick, Braver, Barch, Carter, & Cohen, 2001), the detection of conflict automatically triggers cognitive control mechanisms, which can enhance resolution of subsequent conflict, namely, "conflict adaptation." If adaptation reflects the recruitment of domain-general processes, then conflict detection in one domain should facilitate conflict resolution in an entirely different domain. We report two novel findings: (i) significant conflict adaptation from a syntactic to a non-syntactic domain and (ii) from a perceptual to a verbal domain, providing strong evidence that adaptation is mediated by domain-general cognitive control. PMID:24103774

  15. 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.

  16. 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.``

  17. Conditions under which lorazepam can facilitate retrieval.

    PubMed

    File, S E; Fluck, E; Joyce, E M

    1999-08-01

    Memory is composed of three stages: acquisition, consolidation, and retrieval. By impairing acquisition processes, benzodiazepines cause anterograde amnesia while leaving intact information learned before the drug was taken. In some circumstances, retrieval of this information is even improved by benzodiazepines. It has been hypothesized that this phenomenon is not a true facilitation of retrieval processes, but is the result of reduced interference from items presented after drug administration and is thus a secondary consequence of drug-induced amnesia. Experiment 1 investigated the effect of 0.5, 1, and 2.5 mg of lorazepam on explicit episodic memory in healthy young volunteers. The 1-mg dose was found to significantly improve recall of items presented before drug administration without causing amnesia for items presented after drug administration, thus excluding an interference explanation. Experiment 2 investigated the conditions necessary to obtain facilitated retrieval with 1 mg of lorazepam. The results showed that facilitation was found only when two lists of semantically related material were presented, but that both of the lists could be presented before drug administration, thus excluding an effect of lorazepam on consolidation. Facilitation could be demonstrated in both direct (free recall) and indirect (backwards reading) retrieval tasks and when all of the material was presented after lorazepam administration. This improved retrieval could therefore be of clinical relevance, but any benefits would be reduced at higher doses that at the same time impair acquisition of new information. However, because 1 mg of lorazepam is an effective anxiolytic dose, these results suggest that it is possible to combine effective anxiety reduction with some benefits to memory.

  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. 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

  20. Chimpanzee lip-smacking facilitates cooperative behaviour

    PubMed Central

    Fedurek, Pawel; Slocombe, Katie E.; Hartel, Jessica A.; Zuberbühler, Klaus

    2015-01-01

    Signalling plays an important role in facilitating and maintaining affiliative or cooperative interactions in social animals. Social grooming in primates is an example of an interaction that requires coordination between partners but little is known about communicative behaviours facilitating this activity. In this study, we analysed the communication of wild chimpanzees of Budongo Forest, Uganda, as they entered and maintained a naturally occurring cooperative interaction: social grooming. We found that lip-smacking, a distinct multimodal oral gesture produced during grooming, coordinated this activity. Lip-smacking at the beginning of grooming bouts was significantly more often followed by longer and reciprocated bouts than silent grooming initiations. Lip-smacks were more likely to be produced when the risk of termination of the interaction by the recipient was high, for instance when grooming vulnerable body parts. Groomers were also more likely to produce lip-smacks during face-to-face grooming where the visual aspect of the signal could be perceived. Data are consistent with the hypothesis that chimpanzee lip-smacks function to coordinate and prolong social grooming, suggesting that this oral signal is an example of a communicative behaviour facilitating cooperative behaviour in chimpanzees. PMID:26293777

  1. Selective Activation of Microglia Facilitates Synaptic Strength

    PubMed Central

    Clark, Anna K.; Gruber-Schoffnegger, Doris; Drdla-Schutting, Ruth; Gerhold, Katharina J.; Malcangio, Marzia

    2015-01-01

    Synaptic plasticity is thought to be initiated by neurons only, with the prevailing view assigning glial cells mere specify supportive functions for synaptic transmission and plasticity. We now demonstrate that glial cells can control synaptic strength independent of neuronal activity. Here we show that selective activation of microglia in the rat is sufficient to rapidly facilitate synaptic strength between primary afferent C-fibers and lamina I neurons, the first synaptic relay in the nociceptive pathway. Specifically, the activation of the CX3CR1 receptor by fractalkine induces the release of interleukin-1β from microglia, which modulates NMDA signaling in postsynaptic neurons, leading to the release of an eicosanoid messenger, which ultimately enhances presynaptic neurotransmitter release. In contrast to the conventional view, this form of plasticity does not require enhanced neuronal activity to trigger the events leading to synaptic facilitation. Augmentation of synaptic strength in nociceptive pathways represents a cellular model of pain amplification. The present data thus suggest that, under chronic pain states, CX3CR1-mediated activation of microglia drives the facilitation of excitatory synaptic transmission in the dorsal horn, which contributes to pain hypersensitivity in chronic pain states. PMID:25788673

  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. 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.

  4. 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.

  5. Uniform rotating field network structure to efficiently package a magnetic bubble domain memory

    NASA Technical Reports Server (NTRS)

    Wolfshagen, Ronald G. (Inventor); Ypma, John E. (Inventor); Murray, Glen W. (Inventor); Chen, Thomas T. (Inventor)

    1978-01-01

    A unique and compact open coil rotating magnetic field network structure to efficiently package an array of bubble domain devices is disclosed. The field network has a configuration which effectively enables selected bubble domain devices from the array to be driven in a vertical magnetic field and in an independent and uniform horizontal rotating magnetic field. The field network is suitably adapted to minimize undesirable inductance effects, improve capabilities of heat dissipation, and facilitate repair or replacement of a bubble device.

  6. 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

  7. 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.

  8. 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.

  9. Auxilin facilitates membrane traffic in the early secretory pathway.

    PubMed

    Ding, Jingzhen; Segarra, Verónica A; Chen, Shuliang; Cai, Huaqing; Lemmon, Sandra K; Ferro-Novick, Susan

    2016-01-01

    Coat protein complexes contain an inner shell that sorts cargo and an outer shell that helps deform the membrane to give the vesicle its shape. There are three major types of coated vesicles in the cell: COPII, COPI, and clathrin. The COPII coat complex facilitates vesicle budding from the endoplasmic reticulum (ER), while the COPI coat complex performs an analogous function in the Golgi. Clathrin-coated vesicles mediate traffic from the cell surface and between the trans-Golgi and endosome. While the assembly and structure of these coat complexes has been extensively studied, the disassembly of COPII and COPI coats from membranes is less well understood. We describe a proteomic and genetic approach that connects the J-domain chaperone auxilin, which uncoats clathrin-coated vesicles, to COPII and COPI coat complexes. Consistent with a functional role for auxilin in the early secretory pathway, auxilin binds to COPII and COPI coat subunits. Furthermore, ER-Golgi and intra-Golgi traffic is delayed at 15°C in swa2Δ mutant cells, which lack auxilin. In the case of COPII vesicles, we link this delay to a defect in vesicle fusion. We propose that auxilin acts as a chaperone and/or uncoating factor for transport vesicles that act in the early secretory pathway.

  10. Facilitating functional annotation of chicken microarray data

    PubMed Central

    2009-01-01

    Background Modeling results from chicken microarray studies is challenging for researchers due to little functional annotation associated with these arrays. The Affymetrix GenChip chicken genome array, one of the biggest arrays that serve as a key research tool for the study of chicken functional genomics, is among the few arrays that link gene products to Gene Ontology (GO). However the GO annotation data presented by Affymetrix is incomplete, for example, they do not show references linked to manually annotated functions. In addition, there is no tool that facilitates microarray researchers to directly retrieve functional annotations for their datasets from the annotated arrays. This costs researchers amount of time in searching multiple GO databases for functional information. Results We have improved the breadth of functional annotations of the gene products associated with probesets on the Affymetrix chicken genome array by 45% and the quality of annotation by 14%. We have also identified the most significant diseases and disorders, different types of genes, and known drug targets represented on Affymetrix chicken genome array. To facilitate functional annotation of other arrays and microarray experimental datasets we developed an Array GO Mapper (AGOM) tool to help researchers to quickly retrieve corresponding functional information for their dataset. Conclusion Results from this study will directly facilitate annotation of other chicken arrays and microarray experimental datasets. Researchers will be able to quickly model their microarray dataset into more reliable biological functional information by using AGOM tool. The disease, disorders, gene types and drug targets revealed in the study will allow researchers to learn more about how genes function in complex biological systems and may lead to new drug discovery and development of therapies. The GO annotation data generated will be available for public use via AgBase website and will be updated on regular

  11. Facilitation of glutamate receptors enhances memory.

    PubMed Central

    Staubli, U; Rogers, G; Lynch, G

    1994-01-01

    A benzamide drug that crosses the blood-brain barrier and facilitates DL-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated synaptic responses was tested for its effects on memory in three behavioral tasks. The compound reversibly increased the amplitude and prolonged the duration of field excitatory postsynaptic potentials in hippocampal slices and produced comparable effects in the dentgate gyrus in situ after intraperitoneal injections. Rats injected with the drug 30 min prior to being given a suboptimal number of training trials in a two-odor discrimination task were more likely than controls to select the correct odor in a retention test carried out 96 hr later. Evidence for improved memory was also obtained in a water maze task in which rats were given only four trials to find a submerged platform in the presence of spatial cues; animals injected with the drug 30 min before the training session were significantly faster than vehicle-injected controls in returning to the platform location when tested 24 hr after training. Finally, the drug produced positive effects in a radial maze test of short-term memory. Well trained rats were allowed to retrieve rewards from four arms of an eight-arm maze and then tested for reentry errors 8 hr later. The number of such errors was substantially reduced on days in which the animals were injected with the drug before initial learning. These results indicate that a drug that facilitates glutamatergic transmission enhances the encoding of memory across tasks involving different sensory cues and performance requirements. This may reflect an action on the cellular mechanisms responsible for producing synaptic changes since facilitation of AMPA receptors promotes the induction of the long-term potentiation effect. PMID:8290599

  12. 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. PMID:2298104

  13. Concept Convergence in Empirical Domains

    NASA Astrophysics Data System (ADS)

    Ontañón, Santiago; Plaza, Enric

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

  14. 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.

  15. Dose-response investigation into glucose facilitation of memory performance and mood in healthy young adults.

    PubMed

    Sünram-Lea, Sandra I; Owen, Lauren; Finnegan, Yvonne; Hu, Henglong

    2011-08-01

    It has been suggested that the memory enhancing effect of glucose follows an inverted U-shaped curve, with 25 g resulting in optimal facilitation in healthy young adults. The aim of this study was to further investigate the dose dependency of the glucose facilitation effect in this population across different memory domains and to assess moderation by interindividual differences in glucose regulation and weight. Following a double-blind, repeated measures design, 30 participants were administered drinks containing five different doses of glucose (0 g, 15 g, 25 g, 50 g, and 60 g) and were tested across a range of memory tasks. Glycaemic response and changes in mood state were assessed following drink administration. Analysis of the data showed that glucose administration did not affect mood, but significant glucose facilitation of several memory tasks was observed. However, dose-response curves differed depending on the memory task with only performance on the long-term memory tasks adhering largely to the previously observed inverted U-shaped dose-response curve. Moderation of the response profiles by interindividual differences in glucose regulation and weight was observed. The current data suggest that dose-response function and optimal dose might depend on cognitive domain and are moderated by interindividual differences in glucose regulation and weight.

  16. Facilitation and practice in verb acquisition.

    PubMed

    Keren-Portnoy, Tamar

    2006-08-01

    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 intensive use and common word order errors--and this slows down learning during the early stages of acquiring a structure. The facilitation and practice hypotheses were tested on naturalistic production samples of six Hebrew-acquiring children ranging from ages 1;1 to 2;7 (average ages 1;6 to 2;4 months). Results show that most structures did in fact accelerate; the notion of 'practice' is supported by the inverse correlation found between number of verbs and number of errors in the earliest productions in a given structure; and the absence of acceleration in a minority of the structures is due to the fact that they involve relatively less practice. PMID:17017277

  17. 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.

  18. Pathways by which Abeta facilitates tau pathology.

    PubMed

    Blurton-Jones, Mathew; Laferla, Frank M

    2006-12-01

    Since the initial description one hundred years ago by Dr. Alois Alzheimer, the disorder that bears his name has been characterized by the occurrence of two brain lesions: amyloid plaques and neurofibrillary tangles (NFTs). Yet the precise relationship between beta-amyloid (Abeta) and tau, the two proteins that accumulate within these lesions, has proven elusive. Today, a growing body of work supports the notion that Abeta may directly or indirectly interact with tau to accelerate NFT formation. Here we review recent evidence that Abeta can adversely affect distinct molecular and cellular pathways, thereby facilitating tau phosphorylation, aggregation, mis-localization, and accumulation. Studies are presented that support four putative mechanisms by which Abeta may facilitate the development of tau pathology. A great deal of work suggests that Abeta may drive tau pathology by activating specific kinases, providing a straightforward mechanism by which Abeta may enhance tau hyperphosphorylation and NFT formation. In the AD brain, Abeta also triggers a massive inflammatory response and pro-inflammatory cytokines can in turn indirectly modulate tau phosphorylation. Mounting evidence also suggests that Abeta may inhibit tau degradation via the proteasome. Lastly, Abeta and tau may indirectly interact at the level of axonal transport and evidence is presented for two possible scenarios by which axonal transport deficits may play a role. We propose that the four putative mechanisms described in this review likely mediate the interactions between Abeta and tau, thereby leading to the development of AD neurodegeneration.

  19. Shear stress facilitates tissue-engineered odontogenesis.

    PubMed

    Honda, M J; Shinohara, Y; Sumita, Y; Tonomura, A; Kagami, H; Ueda, M

    2006-07-01

    Numerous studies have demonstrated the effect of shear stress on osteoblasts, but its effect on odontogenic cells has never been reported. In this study, we focused on the effect of shear stress on facilitating tissue-engineered odontogenesis by dissociated single cells. Cells were harvested from the porcine third molar tooth at the early stage of crown formation, and the isolated heterogeneous cells were seeded on a biodegradable polyglycolic acid fiber mesh. Then, cell-polymer constructs with and without exposure to shear stress were evaluated by in vitro and in vivo studies. In in vitro studies, the expression of both epithelial and mesenchymal odontogenic-related mRNAs was significantly enhanced by shear stress for 2 h. At 12 h after exposure to shear stress, the expression of amelogenin, bone sialoprotein and vimentin protein was significantly enhanced compared with that of control. Moreover, after 7 days, alkaline phosphatase activity exhibited a significant increase without any significant effect on cell proliferation in vitro. In vivo, enamel and dentin tissues formed after 15 weeks of in vivo implantation in constructs exposure to in vitro shear stress for 12 h. Such was not the case in controls. We concluded that shear stress facilitates odontogenic cell differentiation in vitro as well as the process of tooth tissue engineering in vivo.

  20. Crystal structure of the human GGA1 GAT domain.

    SciTech Connect

    Zhu, G.; Zhai, P.; He, X.; Terzyan, S.; Zhang, R.; Joachimiak, A.; Tang, J.; Zhang, X. C.; Biosciences Division; Oklahoma Medical Research Foundation; Oklahoma Univ. Medical Center

    2003-06-03

    GGAs are a family of vesicle-coating regulatory proteins that function in intracellular protein transport. A GGA molecule contains four domains, each mediating interaction with other proteins in carrying out intracellular transport. The GAT domain of GGAs has been identified as the structural entity that binds membrane-bound ARF, a molecular switch regulating vesicle-coat assembly. It also directly interacts with rabaptin5, an essential component of endosome fusion. A 2.8 A resolution crystal structure of the human GGA1 GAT domain is reported here. The GAT domain contains four helices and has an elongated shape with the longest dimension exceeding 80 A. Its longest helix is involved in two structural motifs: an N-terminal helix-loop-helix motif and a C-terminal three-helix bundle. The N-terminal motif harbors the most conservative amino acid sequence in the GGA GAT domains. Within this conserved region, a cluster of residues previously implicated in ARF binding forms a hydrophobic surface patch, which is likely to be the ARF-binding site. In addition, a structure-based mutagenesis-biochemical analysis demonstrates that the C-terminal three-helix bundle of this GAT domain is responsible for the rabaptin5 binding. These structural characteristics are consistent with a model supporting multiple functional roles for the GAT domain.

  1. 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.

  2. Best practice in clinical facilitation of undergraduate nursing students.

    PubMed

    Needham, Judith; McMurray, Anne; Shaban, Ramon Z

    2016-09-01

    Clinical facilitation is critical to successful student clinical experience. The research reported in this paper used an interpretive case study to explore perspectives of clinical facilitators on what constitutes best practice in clinical facilitation of undergraduate nursing students. Eleven clinical facilitators from South East Queensland, Australia, participated in focus groups, interviews and a concept mapping exercise to gather their perspectives on best practice. The data gathered information regarding their prior and current experiences as registered nurses and facilitators, considering reasons they became clinical facilitators, their educational background and self-perceived adequacy of their knowledge for clinical facilitation. Analysis was through constant comparison. Findings of the study provided in-depth insight into the role of clinical facilitators, with best practice conceptualised via three main themes; 'assessing', 'learning to facilitate' and 'facilitating effectively'. While they felt there was some autonomy in the role, the clinical facilitators sought a closer liaison with academic staff and feedback about their performance, in particular their assessment of the students. Key strategies identified for improving best practice included educational support for the clinical facilitators, networking, and mentoring from more experienced clinical facilitators. When implemented, these strategies will help develop the clinical facilitators' skills and ensure quality clinical experiences for undergraduate nursing students. PMID:27580169

  3. 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

  4. 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.; 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 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

  5. Structure and Dynamics of Adeno-Associated Virus Serotype 1 VP1-Unique N-Terminal Domain and Its Role in Capsid Trafficking

    PubMed Central

    Venkatakrishnan, Balasubramanian; Yarbrough, Joseph; Domsic, John; Bennett, Antonette; Bothner, Brian; Kozyreva, Olga G.; Samulski, R. Jude; Muzyczka, Nicholas

    2013-01-01

    The importance of the phospholipase A2 domain located within the unique N terminus of the capsid viral protein VP1 (VP1u) in parvovirus infection has been reported. This study used computational methods to characterize the VP1 sequence for adeno-associated virus (AAV) serotypes 1 to 12 and circular dichroism and electron microscopy to monitor conformational changes in the AAV1 capsid induced by temperature and the pHs encountered during trafficking through the endocytic pathway. Circular dichroism was also used to monitor conformational changes in AAV6 capsids assembled from VP2 and VP3 or VP1, VP2, and VP3 at pH 7.5. VP1u was predicted (computationally) and confirmed (in solution) to be structurally ordered. This VP domain was observed to undergo a reversible pH-induced unfolding/refolding process, a loss/gain of α-helical structure, which did not disrupt the capsid integrity and is likely facilitated by its difference in isoelectric point compared to the other VP sequences assembling the capsid. This study is the first to physically document conformational changes in the VP1u region that likely facilitate its externalization from the capsid interior during infection and establishes the order of events in the escape of the AAV capsid from the endosome en route to the nucleus. PMID:23427155

  6. Structure and dynamics of adeno-associated virus serotype 1 VP1-unique N-terminal domain and its role in capsid trafficking.

    PubMed

    Venkatakrishnan, Balasubramanian; Yarbrough, Joseph; Domsic, John; Bennett, Antonette; Bothner, Brian; Kozyreva, Olga G; Samulski, R Jude; Muzyczka, Nicholas; McKenna, Robert; Agbandje-McKenna, Mavis

    2013-05-01

    The importance of the phospholipase A2 domain located within the unique N terminus of the capsid viral protein VP1 (VP1u) in parvovirus infection has been reported. This study used computational methods to characterize the VP1 sequence for adeno-associated virus (AAV) serotypes 1 to 12 and circular dichroism and electron microscopy to monitor conformational changes in the AAV1 capsid induced by temperature and the pHs encountered during trafficking through the endocytic pathway. Circular dichroism was also used to monitor conformational changes in AAV6 capsids assembled from VP2 and VP3 or VP1, VP2, and VP3 at pH 7.5. VP1u was predicted (computationally) and confirmed (in solution) to be structurally ordered. This VP domain was observed to undergo a reversible pH-induced unfolding/refolding process, a loss/gain of α-helical structure, which did not disrupt the capsid integrity and is likely facilitated by its difference in isoelectric point compared to the other VP sequences assembling the capsid. This study is the first to physically document conformational changes in the VP1u region that likely facilitate its externalization from the capsid interior during infection and establishes the order of events in the escape of the AAV capsid from the endosome en route to the nucleus. PMID:23427155

  7. 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…

  8. 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.

  9. Transforming PICU Culture to Facilitate Early Rehabilitation

    PubMed Central

    Hopkins, Ramona O.; Choong, Karen; Zebuhr, Carleen A.; Kudchadkar, Sapna R.

    2016-01-01

    Children who survive a critical illness are at risk of developing significant, long-lasting morbidities that may include neuromuscular weakness, cognitive impairments, and new mental health disorders. These morbidities, collectively known as post–intensive care syndrome (PICS), may lead to functional impairments, difficulty in school and social settings, and reduced quality of life. Interventions aimed at rehabilitation such as early mobilization, sedation minimization and prevention of ICU-acquired weakness, delirium, and posttraumatic stress disorder may lead to improved clinical outcomes and functional recovery in critically ill children. Acute rehabilitation is challenging to implement in a pediatric intensive care unit (PICU), and a culture change is needed to effect widespread transformation in this setting. Our objectives in this article are to review the evidence on PICS in children and strategies for affecting culture change to facilitate early rehabilitation in the PICU. PMID:27134761

  10. 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.

  11. The helical structure of DNA facilitates binding

    NASA Astrophysics Data System (ADS)

    Berg, Otto G.; Mahmutovic, Anel; Marklund, Emil; Elf, Johan

    2016-09-01

    The helical structure of DNA imposes constraints on the rate of diffusion-limited protein binding. Here we solve the reaction-diffusion equations for DNA-like geometries and extend with simulations when necessary. We find that the helical structure can make binding to the DNA more than twice as fast compared to a case where DNA would be reactive only along one side. We also find that this rate advantage remains when the contributions from steric constraints and rotational diffusion of the DNA-binding protein are included. Furthermore, we find that the association rate is insensitive to changes in the steric constraints on the DNA in the helix geometry, while it is much more dependent on the steric constraints on the DNA-binding protein. We conclude that the helical structure of DNA facilitates the nonspecific binding of transcription factors and structural DNA-binding proteins in general.

  12. RGB marking facilitates multicolor clonal cell tracking.

    PubMed

    Weber, Kristoffer; Thomaschewski, Michael; Warlich, Michael; Volz, Tassilo; Cornils, Kerstin; Niebuhr, Birte; Täger, Maike; Lütgehetmann, Marc; Pollok, Jörg-Matthias; Stocking, Carol; Dandri, Maura; Benten, Daniel; Fehse, Boris

    2011-04-01

    We simultaneously transduced cells with three lentiviral gene ontology (LeGO) vectors encoding red, green or blue fluorescent proteins. Individual cells were thereby marked by different combinations of inserted vectors, resulting in the generation of numerous mixed colors, a principle we named red-green-blue (RGB) marking. We show that lentiviral vector-mediated RGB marking remained stable after cell division, thus facilitating the analysis of clonal cell fates in vitro and in vivo. Particularly, we provide evidence that RGB marking allows assessment of clonality after regeneration of injured livers by transplanted primary hepatocytes. We also used RGB vectors to mark hematopoietic stem/progenitor cells that generated colored spleen colonies. Finally, based on limiting-dilution and serial transplantation assays with tumor cells, we found that clonal tumor cells retained their specific color-code over extensive periods of time. We conclude that RGB marking represents a useful tool for cell clonality studies in tissue regeneration and pathology. PMID:21441917

  13. 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. PMID:22897367

  14. Component with inspection-facilitating features

    SciTech Connect

    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.

  15. The helical structure of DNA facilitates binding

    NASA Astrophysics Data System (ADS)

    Berg, Otto G.; Mahmutovic, Anel; Marklund, Emil; Elf, Johan

    2016-09-01

    The helical structure of DNA imposes constraints on the rate of diffusion-limited protein binding. Here we solve the reaction–diffusion equations for DNA-like geometries and extend with simulations when necessary. We find that the helical structure can make binding to the DNA more than twice as fast compared to a case where DNA would be reactive only along one side. We also find that this rate advantage remains when the contributions from steric constraints and rotational diffusion of the DNA-binding protein are included. Furthermore, we find that the association rate is insensitive to changes in the steric constraints on the DNA in the helix geometry, while it is much more dependent on the steric constraints on the DNA-binding protein. We conclude that the helical structure of DNA facilitates the nonspecific binding of transcription factors and structural DNA-binding proteins in general.

  16. 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.

  17. 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.

  18. 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.

  19. Facilitative glucose transporters in livestock species.

    PubMed

    Hocquette, J F; Abe, H

    2000-01-01

    The study of facilitative glucose transporters (GLUT) requires carefully done immunological experiments and sensitive molecular biology approaches to identify the various mechanisms which control GLUT expression at the RNA and protein levels. The cloning of species-specific GLUT cDNAs showed that GLUT4 and GLUT1 diverge less among species than other GLUT isoforms. The key role of GLUT in glucose homeostasis has been demonstrated in livestock species. In vitro studies have suggested specific roles of GLUT1 and GLUT3 in avian cells. In vivo studies have demonstrated a regulation of GLUTs (especially of GLUT4) by nutritional and hormonal factors in pigs and cattle, in lactating cows and goats and throughout the foetal life in the placenta and tissues of lambs and calves. All these results suggest that any changes in GLUT expression and activity (such as GLUT4 in muscles) could modify nutrient partitioning and tissue metabolism, and hence, the qualities of animal products (milk, meat).

  20. 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.

  1. 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.

  2. Dissociative Tendencies and Facilitated Emotional Processing

    PubMed Central

    Oathes, Desmond J.; Ray, William J.

    2009-01-01

    Dissociation is a process linked to lapses of attention, history of abuse or trauma, compromised emotional memory, and a disintegrated sense of self. It is theorized that dissociation stems from avoiding emotional information, especially negative emotion, to protect a fragile psyche. The present study tested whether or not dissociaters do actually avoid processing emotion by asking groups scoring high or low on the Dissociative Experiences Scale to judge the affective valence of several types of emotional stimuli. Manipulations of valence, modality (pictures or words), task complexity, and personal relevance lead to results suggesting that dissociation is linked to facilitated rather than deficient emotional processing. Our results are consistent with a theory that sensitivity to emotional material may be a contributing factor in subsequent dissociation to avoid further elaboration of upsetting emotion in these individuals. The findings for dissociation further exemplify the influence of individual differences in the link between cognition and emotion. PMID:18837615

  3. Brief fear preexposure facilitates subsequent fear conditioning.

    PubMed

    Iwasaki, Satoshi; Sakaguchi, Tetsuya; Ikegaya, Yuji

    2015-06-01

    Post-traumatic stress disorder (PTSD) is an anxiety disorder that occurs following an unexpected exposure to a severe psychological event. A history of a brief trauma is reported to affect a risk for future PTSD development; however, little is known about the mechanisms by which a previous trauma exposure drives the sensitivity to a late-coming trauma. Using a mouse PTSD model, we found that a prior foot shock enhances contextual fear conditioning. This shock-induced facilitation of fear conditioning (i.e., priming effect) persisted for 7 days and was prevented by MK801, an N-methyl-D-aspartate receptor antagonist. Other types of trauma, such as forced swimming or tail pinch, did not induce a priming effect on fear conditioning. Thus, a trauma is unlikely generalized to modify the sensitivity to other traumatic experiences. The behavioral procedure employed in this study may be a useful tool to elucidate the etiology of PTSD.

  4. Cognitive Facilitation Following Intentional Odor Exposure

    PubMed Central

    Johnson, Andrew J.

    2011-01-01

    This paper reviews evidence that, in addition to incidental olfactory pollutants, intentional odor delivery can impact cognitive operations both positively and negatively. Evidence for cognitive facilitation/interference is reviewed alongside four potential explanations for odor-induced effects. It is concluded that the pharmacological properties of odors can induce changes in cognition. However, these effects can be accentuated/attenuated by the shift in mood following odor exposure, expectancy of cognitive effects, and cues to behavior via the contextual association with the odor. It is proposed that greater consideration is required in the intentional utilization of odors within both industrial and private locations, since differential effects are observed for odors with positive hedonic qualities. PMID:22163909

  5. 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.

  6. Domain-specific enhancement of metacognitive ability following meditation training.

    PubMed

    Baird, Benjamin; Mrazek, Michael D; Phillips, Dawa T; Schooler, Jonathan W

    2014-10-01

    Contemplative mental practices aim to enable individuals to develop greater awareness of their own cognitive and affective states through repeated examination of first-person experience. Recent cross-sectional studies of long-term meditation practitioners suggest that the subjective reports of such individuals are better calibrated with objective indices; however, the impact of mental training on metacognitive ability has not yet been examined in a randomized controlled investigation. The present study evaluated the impact of a 2-week meditation-training program on introspective accuracy in the domains of perception and memory. Compared with an active control group that elicited no change, we found that a 2-week meditation program significantly enhanced introspective accuracy, quantified by metacognitive judgments of cognition on a trial-by-trial basis, in a memory but not a perception domain. Together, these data suggest that, in at least some domains, the human capacity to introspect is plastic and can be enhanced through training.

  7. 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.

  8. 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.

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

    PubMed

    Jiang, Daohua; Zhao, Yan; Fan, Junping; Liu, Xuehui; Wu, Yan; Feng, Wei; Zhang, Xuejun C

    2014-07-25

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

  10. Modulated Magnetic Nanowires for Controlling Domain Wall Motion: Toward 3D Magnetic Memories.

    PubMed

    Ivanov, Yurii P; Chuvilin, Andrey; Lopatin, Sergei; Kosel, Jurgen

    2016-05-24

    Cylindrical magnetic nanowires are attractive materials for next generation data storage devices owing to the theoretically achievable high domain wall velocity and their efficient fabrication in highly dense arrays. In order to obtain control over domain wall motion, reliable and well-defined pinning sites are required. Here, we show that modulated nanowires consisting of alternating nickel and cobalt sections facilitate efficient domain wall pinning at the interfaces of those sections. By combining electron holography with micromagnetic simulations, the pinning effect can be explained by the interaction of the stray fields generated at the interface and the domain wall. Utilizing a modified differential phase contrast imaging, we visualized the pinned domain wall with a high resolution, revealing its three-dimensional vortex structure with the previously predicted Bloch point at its center. These findings suggest the potential of modulated nanowires for the development of high-density, three-dimensional data storage devices. PMID:27138460

  11. Modulated Magnetic Nanowires for Controlling Domain Wall Motion: Toward 3D Magnetic Memories.

    PubMed

    Ivanov, Yurii P; Chuvilin, Andrey; Lopatin, Sergei; Kosel, Jurgen

    2016-05-24

    Cylindrical magnetic nanowires are attractive materials for next generation data storage devices owing to the theoretically achievable high domain wall velocity and their efficient fabrication in highly dense arrays. In order to obtain control over domain wall motion, reliable and well-defined pinning sites are required. Here, we show that modulated nanowires consisting of alternating nickel and cobalt sections facilitate efficient domain wall pinning at the interfaces of those sections. By combining electron holography with micromagnetic simulations, the pinning effect can be explained by the interaction of the stray fields generated at the interface and the domain wall. Utilizing a modified differential phase contrast imaging, we visualized the pinned domain wall with a high resolution, revealing its three-dimensional vortex structure with the previously predicted Bloch point at its center. These findings suggest the potential of modulated nanowires for the development of high-density, three-dimensional data storage devices.

  12. Practice-Tailored Facilitation to Improve Pediatric Preventive Care Delivery: A Randomized Trial

    PubMed Central

    Schiltz, Nicholas K.; Sattar, Abdus; Stange, Kurt C.; Nevar, Ann H.; Davey, Christina; Ferretti, Gerald A.; Howell, Diana E.; Strosaker, Robyn; Vavrek, Pamela; Bader, Samantha; Ruhe, Mary C.; Cuttler, Leona

    2014-01-01

    OBJECTIVE: Evolving primary care models require methods to help practices achieve quality standards. This study assessed the effectiveness of a Practice-Tailored Facilitation Intervention for improving delivery of 3 pediatric preventive services. METHODS: In this cluster-randomized trial, a practice facilitator implemented practice-tailored rapid-cycle feedback/change strategies for improving obesity screening/counseling, lead screening, and dental fluoride varnish application. Thirty practices were randomized to Early or Late Intervention, and outcomes assessed for 16 419 well-child visits. A multidisciplinary team characterized facilitation processes by using comparative case study methods. RESULTS: Baseline performance was as follows: for Obesity: 3.5% successful performance in Early and 6.3% in Late practices, P = .74; Lead: 62.2% and 77.8% success, respectively, P = .11; and Fluoride: <0.1% success for all practices. Four months after randomization, performance rose in Early practices, to 82.8% for Obesity, 86.3% for Lead, and 89.1% for Fluoride, all P < .001 for improvement compared with Late practices’ control time. During the full 6-month intervention, care improved versus baseline in all practices, for Obesity for Early practices to 86.5%, and for Late practices 88.9%; for Lead for Early practices to 87.5% and Late practices 94.5%; and for Fluoride, for Early practices to 78.9% and Late practices 81.9%, all P < .001 compared with baseline. Improvements were sustained 2 months after intervention. Successful facilitation involved multidisciplinary support, rapid-cycle problem solving feedback, and ongoing relationship-building, allowing individualizing facilitation approach and intensity based on 3 levels of practice need. CONCLUSIONS: Practice-tailored Facilitation Intervention can lead to substantial, simultaneous, and sustained improvements in 3 domains, and holds promise as a broad-based method to advance pediatric preventive care. PMID:24799539

  13. Predicting cognitive change within domains

    PubMed Central

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

    2010-01-01

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

  14. Functional domain walls in multiferroics

    NASA Astrophysics Data System (ADS)

    Meier, Dennis

    2015-11-01

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

  15. Facilitating Integrated Spatio-Temporal Visualization and Analysis of Heterogeneous Archaeological and Palaeoenvironmental Research Data

    NASA Astrophysics Data System (ADS)

    Willmes, C.; Brocks, S.; Hoffmeister, D.; Hütt, C.; Kürner, D.; Volland, K.; Bareth, G.

    2012-07-01

    In the context of the Collaborative Research Centre 806 "Our way to Europe" (CRC806), a research database is developed for integrating data from the disciplines of archaeology, the geosciences and the cultural sciences to facilitate integrated access to heterogeneous data sources. A practice-oriented data integration concept and its implementation is presented in this contribution. The data integration approach is based on the application of Semantic Web Technology and is applied to the domains of archaeological and palaeoenvironmental data. The aim is to provide integrated spatio-temporal access to an existing wealth of data to facilitate research on the integrated data basis. For the web portal of the CRC806 research database (CRC806-Database), a number of interfaces and applications have been evaluated, developed and implemented for exposing the data to interactive analysis and visualizations.

  16. 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…

  17. 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

  18. Toward a Data Scalable Solution for Facilitating Discovery of Scientific Data Resources

    SciTech Connect

    Chappell, Alan R.; Choudhury, Sutanay; Feo, John T.; Haglin, David J.; Morari, Alessandro; Purohit, Sumit; Schuchardt, Karen L.; Tumeo, Antonino; Weaver, Jesse R.; Villa, Oreste

    2013-11-18

    Science is increasingly motivated by the need to process larger quantities of data. It is facing severe challenges in data collection, management, and processing, so much so that the computational demands of "data scaling" are competing with, and in many fields surpassing, the traditional objective of decreasing processing time. Example domains with large datasets include astronomy, biology, genomic, climate and weather, and material sciences. This paper presents a real-world use case in which we wish to answer queries provided by domain scientists in order to facilitate discovery of relevant science resources. The problem is that the metadata for these science resources is very large and is growing quickly, rapidly increasing the need for a data scaling solution. We propose the use of our SGEM stack -- a system designed for answering graph-based queries over large datasets on cluster architectures -- for answering complex queries over the metadata, and we report early results for our current capability.

  19. The neuritic plaque facilitates pathological conversion of tau in an Alzheimer's disease mouse model

    PubMed Central

    Li, Tong; Braunstein, Kerstin E.; Zhang, Juhong; Lau, Ashley; Sibener, Leslie; Deeble, Christopher; Wong, Philip C.

    2016-01-01

    A central question in Alzheimer's Disease (AD) is whether the neuritic plaque is necessary and sufficient for the development of tau pathology. Hyperphosphorylation of tau is found within dystrophic neurites surrounding β-amyloid deposits in AD mouse models but the pathological conversion of tau is absent. Likewise, expression of a human tau repeat domain in mice is insufficient to drive the pathological conversion of tau. Here we developed an Aβ-amyloidosis mouse model that expresses the human tau repeat domain and show that in these mice, the neuritic plaque facilitates the pathological conversion of wild-type tau. We show that this tau fragment seeds the neuritic plaque-dependent pathological conversion of wild-type tau that spreads from the cortex and hippocampus to the brain stem. These results establish that in addition to the neuritic plaque, a second determinant is required to drive the conversion of wild-type tau. PMID:27373369

  20. Plastic preforms facilitate fabrication of welded cordwood electronic modules

    NASA Technical Reports Server (NTRS)

    Sturman, J. C.

    1968-01-01

    Molded plastic preform facilitates the fabrication of small lots of welded cordwood circuits. The preforms retain the components during welding and electrical checkout and facilitate encapsulation of the welded module when used with a conventional potting shell.

  1. 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)

  2. Massively Parallel Functional Analysis of BRCA1 RING Domain Variants

    PubMed Central

    Starita, Lea M.; Young, David L.; Islam, Muhtadi; Kitzman, Jacob O.; Gullingsrud, Justin; Hause, Ronald J.; Fowler, Douglas M.; Parvin, Jeffrey D.; Shendure, Jay; Fields, Stanley

    2015-01-01

    Interpreting variants of uncertain significance (VUS) is a central challenge in medical genetics. One approach is to experimentally measure the functional consequences of VUS, but to date this approach has been post hoc and low throughput. Here we use massively parallel assays to measure the effects of nearly 2000 missense substitutions in the RING domain of BRCA1 on its E3 ubiquitin ligase activity and its binding to the BARD1 RING domain. From the resulting scores, we generate a model to predict the capacities of full-length BRCA1 variants to support homology-directed DNA repair, the essential role of BRCA1 in tumor suppression, and show that it outperforms widely used biological-effect prediction algorithms. We envision that massively parallel functional assays may facilitate the prospective interpretation of variants observed in clinical sequencing. PMID:25823446

  3. 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.

  4. 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

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

    DOE PAGES

    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 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

  6. Gradient Domain Guided Image Filtering.

    PubMed

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

    2015-11-01

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

  7. 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.

  8. 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

  9. Domain evolution and functional diversification of sulfite reductases.

    PubMed

    Dhillon, Ashita; Goswami, Sulip; Riley, Monica; Teske, Andreas; Sogin, Mitchell

    2005-02-01

    Sulfite reductases are key enzymes of assimilatory and dissimilatory sulfur metabolism, which occur in diverse bacterial and archaeal lineages. They share a highly conserved domain "C-X5-C-n-C-X3-C" for binding siroheme and iron-sulfur clusters that facilitate electron transfer to the substrate. For each sulfite reductase cluster, the siroheme-binding domain is positioned slightly differently at the N-terminus of dsrA and dsrB, while in the assimilatory proteins the siroheme domain is located at the C-terminus. Our sequence and phylogenetic analysis of the siroheme-binding domain shows that sulfite reductase sequences diverged from a common ancestor into four separate clusters (aSir, alSir, dsr, and asrC) that are biochemically distinct; each serves a different assimilatory or dissimilatory role in sulfur metabolism. The phylogenetic distribution and functional grouping in sulfite reductase clusters (dsrA and dsrB vs. aSiR, asrC, and alSir) suggest that their functional diversification during evolution may have preceded the bacterial/archaeal divergence.

  10. Domain Evolution and Functional Diversification of Sulfite Reductases

    NASA Astrophysics Data System (ADS)

    Dhillon, Ashita; Goswami, Sulip; Riley, Monica; Teske, Andreas; Sogin, Mitchell

    2005-02-01

    Sulfite reductases are key enzymes of assimilatory and dissimilatory sulfur metabolism, which occur in diverse bacterial and archaeal lineages. They share a highly conserved domain "C-X5-C-n-C-X3-C" for binding siroheme and iron-sulfur clusters that facilitate electron transfer to the substrate. For each sulfite reductase cluster, the siroheme-binding domain is positioned slightly differently at the N-terminus of dsrA and dsrB, while in the assimilatory proteins the siroheme domain is located at the C-terminus. Our sequence and phylogenetic analysis of the siroheme-binding domain shows that sulfite reductase sequences diverged from a common ancestor into four separate clusters (aSir, alSir, dsr, and asrC) that are biochemically distinct; each serves a different assimilatory or dissimilatory role in sulfur metabolism. The phylogenetic distribution and functional grouping in sulfite reductase clusters (dsrA and dsrB vs. aSiR, asrC, and alSir) suggest that their functional diversification during evolution may have preceded the bacterial/archaeal divergence.

  11. 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…

  12. 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)

  13. Assessing Facilitator Performance as an Influence on Student Satisfaction

    ERIC Educational Resources Information Center

    Dunlap, Scotty; May, David

    2011-01-01

    Growth in class size within the online environment has resulted in a facilitator model in which an instructor teaches the class with the assistance of facilitators who interact with students in smaller groups. This research sought to determine the effectiveness of a structured performance evaluation for facilitators and the correlation to student…

  14. Facilitating the Design of a Campus Leadership Team

    ERIC Educational Resources Information Center

    Meyers, Renee A.; Johnson, John R.

    2008-01-01

    This essay describes how we facilitated the design of a campus leadership team. What is particularly interesting about this consultative project is that both authors participated--one as facilitator and the other as participant. The facilitation included a needs assessment prior to the event, the use of structured controversy techniques,…

  15. 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... § 537.418 Facilitating new investment. Consistent with § 537.530, U.S. persons may approve, finance, facilitate, or guarantee new investment by foreign persons provided such new investment is not pursuant to...

  16. The facilitator: as teams battle to be effective.

    PubMed

    McChesney, H

    1995-05-01

    In this article, you will learn the role facilitators play in team operations, including several power and authority models that can be used. Various group dynamics that facilitators must deal with in team situations will be identified. A suggested facilitator training curriculum is also included.

  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. The NR4A2 Nuclear Receptor Is Recruited to Novel Nuclear Foci in Response to UV Irradiation and Participates in Nucleotide Excision Repair

    PubMed Central

    Harrison, Matthew; Lim, Wen; Muscat, George E. O.; Sturm, Richard A.; Smith, Aaron G.

    2013-01-01

    Ultraviolet radiation (UVR) is one of the most common mutagens encountered by humans and induces the formation of cyclobutane pyrimidine dimers (CPDs) and pyrimidine-(6-4)-pyrimidone photoproduct (6-4PP) lesions in the genomic DNA. To prevent the accumulation of deleterious mutations these lesions must be efficiently repaired, primarily by nucleotide excision repair. We have previously demonstrated that the NR4A family of nuclear receptors are crucial mediators of the DNA repair function of the MC1R signalling pathway in melanocytes. Here we explore the role of the NR4A2 protein in the DNA repair process further. Using EYFP tagged-NR4A2 we have demonstrated a UVR induced recruitment to distinct nuclear foci where they co-localise with known DNA repair proteins. We reveal that the N-terminal domain of the receptor is required for this translocation and identify a role for p38 and PARP signalling in this process. Moreover disruption of the functional integrity of the Ligand Binding Domain of the receptor by deleting the terminal helix 12 effectively blocks co-localisation of the receptor with DNA repair factors. Restored co-localisation of the mutant receptor with DNA repair proteins in the presence of a Histone Deacetylase Inhibitor suggests that impaired chromatin accessibility underpins the mis-localisation observed. Finally NR4A2 over-expression facilitated a more efficient clearance of UVR induced CPD and 6-4PP lesions. Taken together these data uncover a novel role for the NR4A nuclear receptors as direct facilitators of nucleotide excision repair. PMID:24223135

  19. Arthroscopically assisted medial meniscal allograft transplantation using a modified bone plug to facilitate passage: surgical technique.

    PubMed

    Kim, Jin Goo; Lee, Yong Seuk; Lee, Soo Won; Kim, Young Jae; Kong, Doo Hwan; Ko, Min Soo

    2009-07-01

    This article describes a novel medial meniscal allograft transplantation method that permits easy passage of posterior bone plugs and facilitates bone-to-bone healing. With this method, an anterior bone plug with a long cylindrical shape is prepared, and the posterior bone plug is prepared using only a 2-mm deep, flat bone shell containing cancellous material with 6 baseball Ethibond stitches placed around it. The graft is divided into 3 portions, and boundaries of each are marked. Using a posteromedial portal, the posterior bony bed is prepared directly, and the exact anatomic location is visualized. This modified method facilitates graft passage as well as bone-to-bone healing.

  20. 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…

  1. Domain Specificity and Variability in Cognitive Development.

    ERIC Educational Resources Information Center

    Gelman, Rochel

    2000-01-01

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

  2. 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. PMID:20550963

  3. Protected areas facilitate species' range expansions.

    PubMed

    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

    2012-08-28

    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

  4. 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

  5. Environmental stress, facilitation, competition, and coexistence.

    PubMed

    Hart, Simon P; Marshall, Dustin J

    2013-12-01

    The major theories regarding the combined influence of the environment and species interactions on population and community dynamics appear to conflict. Stress/ disturbance gradient models of community organization, such as the stress gradient hypothesis, emphasize a diminished role for competition in harsh environments whereas modern coexistence theory does not. Confusion about the role of species interactions in harsh environments is perpetuated by a disconnect between population dynamics theory and data. We linked theory and data using response surface experiments done in the field to parameterize mathematical, population-dynamic competition models. We replicated our experiment across two environments that spanned a common and important environmental stress gradient for determining community structure in benthic marine systems. We generated quantitative estimates of the effects of environmental stress on population growth rates and the direction and strength of intra- and interspecific interactions within each environment. Our approach directly addressed a perpetual blind spot in this field by showing how the effects of competition can be intensified in stressful environments even though the apparent strength of competition remains unchanged. Furthermore, we showed how simultaneous, reciprocal competitive and facilitative effects can stabilize population dynamics in multispecies communities in stressful environments.

  6. Protein crystallization facilitated by molecularly imprinted polymers

    PubMed Central

    Saridakis, Emmanuel; Khurshid, Sahir; Govada, Lata; Phan, Quan; Hawkins, Daniel; Crichlow, Gregg V.; Lolis, Elias; Reddy, Subrayal M.; Chayen, Naomi E.

    2011-01-01

    We present a previously undescribed initiative and its application, namely the design of molecularly imprinted polymers (MIPs) for producing protein crystals that are essential for determining high-resolution 3D structures of proteins. MIPs, also referred to as “smart materials,” are made to contain cavities capable of rebinding protein; thus the fingerprint of the protein created on the polymer allows it to serve as an ideal template for crystal formation. We have shown that six different MIPs induced crystallization of nine proteins, yielding crystals in conditions that do not give crystals otherwise. The incorporation of MIPs in screening experiments gave rise to crystalline hits in 8–10% of the trials for three target proteins. These hits would have been missed using other known nucleants. MIPs also facilitated the formation of large single crystals at metastable conditions for seven proteins. Moreover, the presence of MIPs has led to faster formation of crystals in all cases where crystals would appear eventually and to major improvement in diffraction in some cases. The MIPs were effective for their cognate proteins and also for other proteins, with size compatibility being a likely criterion for efficacy. Atomic force microscopy (AFM) measurements demonstrated specific affinity between the MIP cavities and a protein-functionalized AFM tip, corroborating our hypothesis that due to the recognition of proteins by the cavities, MIPs can act as nucleation-inducing substrates (nucleants) by harnessing the proteins themselves as templates. PMID:21690356

  7. Audiovisual integration facilitates unconscious visual scene processing.

    PubMed

    Tan, Jye-Sheng; Yeh, Su-Ling

    2015-10-01

    Meanings of masked complex scenes can be extracted without awareness; however, it remains unknown whether audiovisual integration occurs with an invisible complex visual scene. The authors examine whether a scenery soundtrack can facilitate unconscious processing of a subliminal visual scene. The continuous flash suppression paradigm was used to render a complex scene picture invisible, and the picture was paired with a semantically congruent or incongruent scenery soundtrack. Participants were asked to respond as quickly as possible if they detected any part of the scene. Release-from-suppression time was used as an index of unconscious processing of the complex scene, which was shorter in the audiovisual congruent condition than in the incongruent condition (Experiment 1). The possibility that participants adopted different detection criteria for the 2 conditions was excluded (Experiment 2). The audiovisual congruency effect did not occur for objects-only (Experiment 3) and background-only (Experiment 4) pictures, and it did not result from consciously mediated conceptual priming (Experiment 5). The congruency effect was replicated when catch trials without scene pictures were added to exclude participants with high false-alarm rates (Experiment 6). This is the first study demonstrating unconscious audiovisual integration with subliminal scene pictures, and it suggests expansions of scene-perception theories to include unconscious audiovisual integration.

  8. Batten disease: features to facilitate early diagnosis

    PubMed Central

    Collins, J; Holder, G E; Herbert, H; Adams, G G W

    2006-01-01

    Aims To ascertain the clinical and electrophysiological features in patients with juvenile neuronal ceroid lipofuscinosis (jNCL/Batten disease) and to identify those features that facilitate early diagnosis. Methods Nine patients with jNCL were identified retrospectively and their case notes reviewed. All had undergone an extensive clinical examination, including electrophysiology. Blood and molecular genetic testing confirmed the diagnosis. Results Age at onset ranged from 4–8 years. At presentation, two of nine patients had normal fundi; only two of nine patients had a bull's eye maculopathy. The electroretinogram (ERG) findings in this series included undetectable rod specific ERGs, an electronegative maximal response, reduced and delayed cone flicker ERGs, reduction in the b:a ratio in the photopic single flash ERG, and an undetectable pattern ERG. Vacuolated lymphocytes on peripheral blood film testing were present in eight of nine patients. Five of eight patients were homozygous for the 1.02 kb deletion on the CLN3 gene on molecular genetic testing; two of eight patients were heterozygous for that deletion. Conclusion jNCL should be considered in children of 10 years and under presenting with visual loss and fundal changes ranging from normal through to pigmentary/atrophic changes or a bull's eye maculopathy. Electrophysiology may suggest jNCL. Although currently untreatable, early diagnosis is important to institute appropriate counselling and support. PMID:16754648

  9. 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.

  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. 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

  12. Oxytocin facilitates the sensation of social stress.

    PubMed

    Eckstein, Monika; Scheele, Dirk; Weber, Kristina; Stoffel-Wagner, Birgit; Maier, Wolfgang; Hurlemann, René

    2014-09-01

    Essentially all social species experience social stress which can be a catalyst for detriments in mental and physical health. The neuropeptide oxytocin (OXT) has been shown to produce anxiolytic and antistress effects, thereby qualifying the OXT system as a promising drug target in the treatment of stress-related disorders. However, recently it has been shown that OXT can have anxiogenic effects as well. In the present study, we used functional magnetic resonance imaging to scan the brains of 60 healthy men while they were exposed to social stress after they received either intranasal OXT (24 IU) or placebo treatment. Although OXT administration did not alter salivary cortisol levels as a surrogate marker of stress axis activity, our participants initially reported an increment in perceived social stress. This behavioral effect was paralleled on the neural level by increased activity in the precuneus and cingulate cortex. Taken together, our results support the hypothesis that OXT can induce a self-referential processing bias which facilitates the sensation of social stress in the absence of altered endocrine responses.

  13. 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).

  14. 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.

  15. Facilitating nurturant fathering behavior in the NICU.

    PubMed

    Novak, J C

    1990-09-01

    Many of the roles required of the father of a NICU infant are new and unfamiliar, difficult to carry out, unrehearsed, and yet called for in an unexpected crisis. At a time when they too need nurturing, fathers of high-risk infants are expected to adapt readily and be models of self-control. It is apparent from this investigation that the primary nurse is in a strategic position to assist the new father in his acquaintance with and early adjustment to his infant. Although some of the fathers will become actively involved with their children, others prefer less involvement in infant care taking and display minimal nurturant behaviors. A nurse must be able to recognize these differences and support a father's (and mother's) choice. A couple's sociocultural ideology and perceptions of the father's role, as well as the family dynamics and values, need to be given primary consideration in planning nursing care. In order for the nurse to fulfill an important teaching role for the fathers (parents) of NICU infants, the nurse must meet the needs of each individual father in relation to the family system. This requires systematic and nonjudgmental assessment and caring facilitation of paternal role development and early father-infant and father-mother-infant interactions.

  16. Training facilitates object recognition in cubist paintings.

    PubMed

    Wiesmann, Martin; Ishai, Alumit

    2010-01-01

    To the naïve observer, cubist paintings contain geometrical forms in which familiar objects are hardly recognizable, even in the presence of a meaningful title. We used fMRI to test whether a short training session about Cubism would facilitate object recognition in paintings by Picasso, Braque and Gris. Subjects, who had no formal art education, were presented with titled or untitled cubist paintings and scrambled images, and performed object recognition tasks. Relative to the control group, trained subjects recognized more objects in the paintings, their response latencies were significantly shorter, and they showed enhanced activation in the parahippocampal cortex, with a parametric increase in the amplitude of the fMRI signal as a function of the number of recognized objects. Moreover, trained subjects were slower to report not recognizing any familiar objects in the paintings and these longer response latencies were correlated with activation in a fronto-parietal network. These findings suggest that trained subjects adopted a visual search strategy and used contextual associations to perform the tasks. Our study supports the proactive brain framework, according to which the brain uses associations to generate predictions. PMID:20224810

  17. 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

  18. A Traceability Framework to facilitate model evaluation

    NASA Astrophysics Data System (ADS)

    Luo, Yiqi; Xia, Jianyang; Hararuk, Sasha; Wang, Ying Ping

    2013-04-01

    Land models have been developed to account for more and more processes, making their complex structures difficult to be understood and evaluated. Here we introduced a framework to decompose a complex land model into traceable components based on their mutually independent properties of modeled biogeochemical processes. The framework traces modeled ecosystem carbon storage capacity (Xss) to (1) a product of net primary productivity (NPP) and ecosystem residence time (τ_E). The latter τE can be further traced to (2) baseline carbon residence times (τ_(E )^'), which are usually preset in a model according to vegetation characteristics and soil types, (3) environmental scalars (ξ) including temperature and water scalars, and (4) environmental forcings. We have applied the framework to the Australian Community Atmosphere Biosphere Land Exchange (CABLE) model to help understand differences in modeled carbon processes among biomes and as influenced by nitrogen processes. Our framework could be used to facilitate data-model comparisons and model intercomparisons via tracking a few traceable components for all terrestrial carbon cycle models.

  19. Repeated intravenous doxapram induces phrenic motor facilitation

    PubMed Central

    Sandhu, MS; Lee, KZ; Gonzalez-Rothi, EJ; Fuller, DD

    2013-01-01

    Doxapram is a respiratory stimulant used to treat hypoventilation. Here we investigated whether doxapram could also trigger respiratory neuroplasticity. Specifically, we hypothesized that intermittent delivery of doxapram at low doses would lead to long-lasting increases (i.e., facilitation) of phrenic motor output in anesthetized, vagotomized, and mechanically-ventilated rats. Doxapram was delivered intravenously in a single bolus (2 or 6 mg/kg) or as a series of 3 injections (2 mg/kg) at 5 min intervals. Control groups received pH-matched saline injections (vehicle) or no treatment (anesthesia time control). Doxapram evoked an immediate increase in phrenic output in all groups, but a persistent increase in burst amplitude only occurred after repeated dosing with 2 mg/kg. At 60 min following the last injection, phrenic burst amplitude was 168±24% of baseline (%BL) in the group receiving 3 injections (P < 0.05 vs. controls), but was 103±8%BL and 112±4%BL in the groups receiving a single dose of 2 or 6 mg/kg, respectively. Following bilateral section of the carotid sinus nerves, the acute phrenic response to doxapram (2 mg/kg) was reduced by 68% suggesting that at low doses the drug was acting primarily via the carotid chemoreceptors. We conclude that intermittent application of doxapram can trigger phrenic neuroplasticity, and this approach might be of use in the context of respiratory rehabilitation following neurologic injury. PMID:24013015

  20. 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

  1. 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. PMID:24918706

  2. Environmental stress, facilitation, competition, and coexistence.

    PubMed

    Hart, Simon P; Marshall, Dustin J

    2013-12-01

    The major theories regarding the combined influence of the environment and species interactions on population and community dynamics appear to conflict. Stress/ disturbance gradient models of community organization, such as the stress gradient hypothesis, emphasize a diminished role for competition in harsh environments whereas modern coexistence theory does not. Confusion about the role of species interactions in harsh environments is perpetuated by a disconnect between population dynamics theory and data. We linked theory and data using response surface experiments done in the field to parameterize mathematical, population-dynamic competition models. We replicated our experiment across two environments that spanned a common and important environmental stress gradient for determining community structure in benthic marine systems. We generated quantitative estimates of the effects of environmental stress on population growth rates and the direction and strength of intra- and interspecific interactions within each environment. Our approach directly addressed a perpetual blind spot in this field by showing how the effects of competition can be intensified in stressful environments even though the apparent strength of competition remains unchanged. Furthermore, we showed how simultaneous, reciprocal competitive and facilitative effects can stabilize population dynamics in multispecies communities in stressful environments. PMID:24597219

  3. 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.

  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. 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…

  6. Cellulose binding domain fusion proteins

    DOEpatents

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

    1998-01-01

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

  7. 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

  8. 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.

  9. Endpoint distinctiveness facilitates analogical mapping in pigeons.

    PubMed

    Hagmann, Carl Erick; Cook, Robert G

    2015-03-01

    Analogical thinking necessitates mapping shared relations across two separate domains. We investigated whether pigeons could learn faster with ordinal mapping of relations across two physical dimensions (circle size & choice spatial position) relative to random mapping of these relations. Pigeons were trained to relate six circular samples of different sizes to horizontally positioned choice locations in a six alternative matching-to-sample task. Three pigeons were trained in a mapped condition in which circle size mapped directly onto choice spatial position. Three other pigeons were trained in a random condition in which the relations between size and choice position were arbitrarily assigned. The mapped group showed an advantage over the random group in acquiring this task. In a subsequent second phase, relations between the dimensions were ordinally reversed for the mapped group and re-randomized for the random group. There was no difference in how quickly matching accuracy re-emerged in the two groups, although the mapped group eventually performed more accurately. Analyses suggested this mapped advantage was likely due to endpoint distinctiveness and the benefits of proximity errors during choice responding rather than a conceptual or relational advantage attributable to the common or ordinal mapping of the two dimensions. This potential difficulty in mapping relations across dimensions may limit the pigeons' capacity for more advanced types of analogical reasoning. This article is part of a Special Issue entitled: Tribute to Tom Zentall.

  10. Natural frequencies facilitate diagnostic inferences of managers.

    PubMed

    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

  11. Facilitating undergraduate nurses clinical practicum: the lived experience of clinical facilitators.

    PubMed

    Dickson, Cathy; Walker, Jane; Bourgeois, Sharon

    2006-07-01

    Clinical practicum experience for undergraduate nurses remains undisputed as an essential component of any program. Exposure to the reality of professional practice and its integration of explicit, with tacit knowledge, is invaluable in producing skilled clinicians. Currently there are many issues that have arisen regarding clinical practice education for undergraduate nurses in Australia including; ongoing financial support and resourcing of clinical placements. Developing an understanding of these issues is central to the provision of quality clinical education. The aim of this study is to reveal dimensions of the lived experience of being a clinical facilitator, a popular model of nursing clinical education, to come to an understanding of how facilitation actually takes place in the clinical environment. The Hermeneutic phenomenological approach used in this study has brought to light five essential themes that elucidate the phenomena of facilitation. Those themes have been identified as; knowing your own limitations, employing the notion of stepping in or stepping back, developing alliances, acknowledging the reciprocity of the learning experience, and identifying appropriate clinical buddies. The recommendations from this study will have an impact on current issues and will inturn, influence the quality of clinical education for all stakeholders.

  12. Groundwater seeps facilitate exposure to Burkholderia pseudomallei.

    PubMed

    Baker, Anthony; Tahani, Donald; Gardiner, Christopher; Bristow, Keith L; Greenhill, Andrew R; Warner, Jeffrey

    2011-10-01

    Burkholderia pseudomallei is a saprophytic bacterium which is the causative agent of melioidosis, a common cause of fatal bacterial pneumonia and sepsis in the tropics. The incidence of melioidosis is clustered spatially and temporally and is heavily linked to rainfall and extreme weather events. Clinical case clustering has recently been reported in Townsville, Australia, and has implicated Castle Hill, a granite monolith in the city center, as a potential reservoir of infection. Topsoil and water from seasonal groundwater seeps were collected around the base of Castle Hill and analyzed by quantitative real-time PCR targeting the type III secretion system genes for the presence of B. pseudomallei. The organism was identified in 65% (95% confidence interval [CI], 49.5 to 80.4) of soil samples (n = 40) and 92.5% (95% CI, 83.9 to 100) of seasonal groundwater samples (n = 40). Further sampling of water collected from roads and gutters in nearby residential areas after an intense rainfall event found that 88.2% (95% CI, 72.9 to 100) of samples (n = 16) contained viable B. pseudomallei at concentrations up to 113 CFU/ml. Comparison of isolates using multilocus sequence typing demonstrated clinical matches and close associations between environmental isolates and isolates derived from clinical samples from patients in Townsville. This study demonstrated that waterborne B. pseudomallei from groundwater seeps around Castle Hill may facilitate exposure to B. pseudomallei and contribute to the clinical clustering at this site. Access to this type of information will advise the development and implementation of public health measures to reduce the incidence of melioidosis.

  13. Imperfect information facilitates the evolution of reciprocity.

    PubMed

    Kurokawa, Shun

    2016-06-01

    The existence of cooperation demands explanation since cooperation is costly to the actor. Reciprocity has long been regarded as a potential explanatory mechanism for the existence of cooperation. Reciprocity is a mechanism wherein a cooperator responds to an opponent's behavior by switching his/her own behavior. Hence, a possible problematic case relevant to the theory of reciprocity evolution arises when the mechanism is such that the information regarding an opponent's behavior is imperfect. Although it has been confirmed also by previous theoretical studies that imperfect information interferes with the evolution of reciprocity, this argument is based on the assumption that there are no mistakes in behavior. And, a previous study presumed that it might be expected that when such mistakes occur, reciprocity can more readily evolve in the case of imperfect information than in the case of perfect information. The reason why the previous study considers so is that in the former case, reciprocators can miss defections incurred by other reciprocators' mistakes due to imperfect information, allowing cooperation to persist when such reciprocators meet. However, contrary to this expectation, the previous study has shown that even when mistakes occur, imperfect information interferes with the evolution of reciprocity. Nevertheless, the previous study assumed that payoffs are linear (i.e., that the effect of behavior is additive and there are no synergetic effects). In this study, we revisited the same problem but removed the assumption that payoffs are linear. We used evolutionarily stable strategy analysis to compare the condition for reciprocity to evolve when mistakes occur and information is imperfect with the condition for reciprocity to evolve when mistakes occur and information is perfect. Our study revealed that when payoffs are not linear, imperfect information can facilitate the evolution of reciprocity when mistakes occur; while when payoffs are linear

  14. Tonoplast Aquaporins Facilitate Lateral Root Emergence.

    PubMed

    Reinhardt, Hagen; Hachez, Charles; Bienert, Manuela Désirée; Beebo, Azeez; Swarup, Kamal; Voß, Ute; Bouhidel, Karim; Frigerio, Lorenzo; Schjoerring, Jan K; Bennett, Malcolm J; Chaumont, Francois

    2016-03-01

    Aquaporins (AQPs) are water channels allowing fast and passive diffusion of water across cell membranes. It was hypothesized that AQPs contribute to cell elongation processes by allowing water influx across the plasma membrane and the tonoplast to maintain adequate turgor pressure. Here, we report that, in Arabidopsis (Arabidopsis thaliana), the highly abundant tonoplast AQP isoforms AtTIP1;1, AtTIP1;2, and AtTIP2;1 facilitate the emergence of new lateral root primordia (LRPs). The number of lateral roots was strongly reduced in the triple tip mutant, whereas the single, double, and triple tip mutants showed no or minor reduction in growth of the main root. This phenotype was due to the retardation of LRP emergence. Live cell imaging revealed that tight spatiotemporal control of TIP abundance in the tonoplast of the different LRP cells is pivotal to mediating this developmental process. While lateral root emergence is correlated to a reduction of AtTIP1;1 and AtTIP1;2 protein levels in LRPs, expression of AtTIP2;1 is specifically needed in a restricted cell population at the base, then later at the flanks, of developing LRPs. Interestingly, the LRP emergence phenotype of the triple tip mutants could be fully rescued by expressing AtTIP2;1 under its native promoter. We conclude that TIP isoforms allow the spatial and temporal fine-tuning of cellular water transport, which is critically required during the highly regulated process of LRP morphogenesis and emergence.

  15. 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. PMID:25447376

  16. 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

  17. 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

  18. 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

  19. Nucleation, growth, and control of ferroelectric-ferroelastic domains in thin polycrystalline films

    NASA Astrophysics Data System (ADS)

    Ivry, Yachin; Scott, James F.; Salje, Ekhard K. H.; Durkan, Colm

    2012-11-01

    The unique response of ferroic materials to external excitations facilitates them for diverse technologies, such as nonvolatile memory devices. The primary driving force behind this response is encoded in domain switching. In bulk ferroics, domains switch in a two-step process: nucleation and growth. For ferroelectrics, this can be explained by the Kolmogorov-Avrami-Ishibashi (KAI) model. Nevertheless, it is unclear whether domains remain correlated in finite geometries, as required by the KAI model. Moreover, although ferroelastic domains exist in many ferroelectrics, experimental limitations have hindered the study of their switching mechanisms. This uncertainty limits our understanding of domain switching and controllability, preventing thin-film and polycrystalline ferroelectrics from reaching their full technological potential. Here we used piezoresponse force microscopy to study the switching mechanisms of ferroelectric-ferroelastic domains in thin polycrystalline Pb0.7Zr0.3TiO3 films at the nanometer scale. We have found that switched biferroic domains can nucleate at multiple sites with a coherence length that may span several grains, and that nucleators merge to form mesoscale domains, in a manner consistent with that expected from the KAI model.

  20. 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.

  1. A triple-arginine motif in the amino-terminal domain and oligomerization are required for HIV-1 inhibition by human MX2.

    PubMed

    Goujon, Caroline; Greenbury, Rebecca A; Papaioannou, Stelios; Doyle, Tomas; Malim, Michael H

    2015-04-01

    We have employed molecular genetic approaches to understand the domain organization of the HIV-1 resistance factor myxovirus resistance 2 (MX2). First, we describe an essential triple-arginine motif in the amino-terminal domain. Second, we demonstrate that this 91-residue domain mediates antiviral activity when appended to heterologous proteins, and we provide genetic evidence that protein oligomerization is required for MX2 function. These insights will facilitate future work aiming to elucidate MX2's mechanism of action.

  2. Competition and cooperation among similar representations: toward a unified account of facilitative and inhibitory effects of lexical neighbors.

    PubMed

    Chen, Qi; Mirman, Daniel

    2012-04-01

    One of the core principles of how the mind works is the graded, parallel activation of multiple related or similar representations. Parallel activation of multiple representations has been particularly important in the development of theories and models of language processing, where coactivated representations (neighbors) have been shown to exhibit both facilitative and inhibitory effects on word recognition and production. Researchers generally ascribe these effects to interactive activation and competition, but there is no unified explanation for why the effects are facilitative in some cases and inhibitory in others. We present a series of simulations of a simple domain-general interactive activation and competition model that is broadly consistent with more specialized domain-specific models of lexical processing. The results showed that interactive activation and competition can indeed account for the complex pattern of reversals. Critically, the simulations revealed a core computational principle that determines whether neighbor effects are facilitative or inhibitory: strongly active neighbors exert a net inhibitory effect, and weakly active neighbors exert a net facilitative effect.

  3. Cross-domain human action recognition.

    PubMed

    Bian, Wei; Tao, Dacheng; Rui, Yong

    2012-04-01

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

  4. 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.

  5. Saturated Zone Colloid-Facilitated Transport

    SciTech Connect

    A. Wolfsberg; P. Reimus

    2001-12-18

    The purpose of the Saturated Zone Colloid-Facilitated Transport Analysis and Modeling Report (AMR), as outlined in its Work Direction and Planning Document (CRWMS M&O 1999a), is to provide retardation factors for colloids with irreversibly-attached radionuclides, such as plutonium, in the saturated zone (SZ) between their point of entrance from the unsaturated zone (UZ) and downgradient compliance points. Although it is not exclusive to any particular radionuclide release scenario, this AMR especially addresses those scenarios pertaining to evidence from waste degradation experiments, which indicate that plutonium and perhaps other radionuclides may be irreversibly attached to colloids. This report establishes the requirements and elements of the design of a methodology for calculating colloid transport in the saturated zone at Yucca Mountain. In previous Total Systems Performance Assessment (TSPA) analyses, radionuclide-bearing colloids were assumed to be unretarded in their migration. Field experiments in fractured tuff at Yucca Mountain and in porous media at other sites indicate that colloids may, in fact, experience retardation relative to the mean pore-water velocity, suggesting that contaminants associated with colloids should also experience some retardation. Therefore, this analysis incorporates field data where available and a theoretical framework when site-specific data are not available for estimating plausible ranges of retardation factors in both saturated fractured tuff and saturated alluvium. The distribution of retardation factors for tuff and alluvium are developed in a form consistent with the Performance Assessment (PA) analysis framework for simulating radionuclide transport in the saturated zone. To improve on the work performed so far for the saturated-zone flow and transport modeling, concerted effort has been made in quantifying colloid retardation factors in both fractured tuff and alluvium. The fractured tuff analysis used recent data

  6. Spline interpolation on unbounded domains

    NASA Astrophysics Data System (ADS)

    Skeel, Robert D.

    2016-06-01

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

  7. Frequency domain optical parametric amplification

    NASA Astrophysics Data System (ADS)

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

    2014-05-01

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

  8. 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.

  9. 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

  10. Domain decomposition methods in aerodynamics

    NASA Technical Reports Server (NTRS)

    Venkatakrishnan, V.; Saltz, Joel

    1990-01-01

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

  11. 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.

  12. Field-Domain Ion Spectrometry

    NASA Technical Reports Server (NTRS)

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

    1992-01-01

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

  13. Pyramidal inversion domain boundaries revisited

    SciTech Connect

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

    2011-10-03

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

  14. Dynamics of domain wall networks

    SciTech Connect

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

    2007-12-15

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

  15. Aversive control: A separate domain?

    PubMed Central

    Hineline, Philip N.

    1984-01-01

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

  16. Aversive control: A separate domain?

    PubMed

    Hineline, P N

    1984-11-01

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

  17. Aversive control: A separate domain?

    PubMed

    Hineline, P N

    1984-11-01

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

  18. 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.

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

    PubMed Central

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

    2015-01-01

    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. PMID:26070558

  20. Biophysical Analysis of the MHR Motif in Folding and Domain Swapping of the HIV Capsid Protein C-Terminal Domain

    PubMed Central

    Bocanegra, Rebeca; Fuertes, Miguel Ángel; Rodríguez-Huete, Alicia; Neira, José Luis; Mateu, Mauricio G.

    2015-01-01

    Infection by human immunodeficiency virus (HIV) depends on the function, in virion morphogenesis and other stages of the viral cycle, of a highly conserved structural element, the major homology region (MHR), within the carboxyterminal domain (CTD) of the capsid protein. In a modified CTD dimer, MHR is swapped between monomers. While no evidence for MHR swapping has been provided by structural models of retroviral capsids, it is unknown whether it may occur transiently along the virus assembly pathway. Whatever the case, the MHR-swapped dimer does provide a novel target for the development of anti-HIV drugs based on the concept of trapping a nonnative capsid protein conformation. We have carried out a thermodynamic and kinetic characterization of the domain-swapped CTD dimer in solution. The analysis includes a dissection of the role of conserved MHR residues and other amino acids at the dimerization interface in CTD folding, stability, and dimerization by domain swapping. The results revealed some energetic hotspots at the domain-swapped interface. In addition, many MHR residues that are not in the protein hydrophobic core were nevertheless found to be critical for folding and stability of the CTD monomer, which may dramatically slow down the swapping reaction. Conservation of MHR residues in retroviruses did not correlate with their contribution to domain swapping, but it did correlate with their importance for stable CTD folding. Because folding is required for capsid protein function, this remarkable MHR-mediated conformational stabilization of CTD may help to explain the functional roles of MHR not only during immature capsid assembly but in other processes associated with retrovirus infection. This energetic dissection of the dimerization interface in MHR-swapped CTD may also facilitate the design of anti-HIV compounds that inhibit capsid assembly by conformational trapping of swapped CTD dimers. PMID:25606682

  1. 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.

  2. 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. PMID:27101707

  3. Inter-domain interactions of TDP-43 as decoded by NMR.

    PubMed

    Wei, Yuanyuan; Lim, Liangzhong; Wang, Lu; Song, Jianxing

    2016-04-29

    TDP-43 inclusions have been found in ∼97% ALS as well as an increasing spectrum of other neurodegenerative diseases including Alzheimer's. TDP-43 contains an ubiquitin-like fold, two RRMs and a prion-like domain, but whether they interact with each other remains unknown due to being intrinsically aggregation-prone. Nevertheless, this knowledge is pivotal to understanding physiological functions and pathological roles of TDP-43. Here as facilitated by our previous discovery which allowed NMR characterization of TDP-43 and its five dissected fragments, we successfully decoded that TDP-43 does have dynamic inter-domain interactions, which are coordinated by the intrinsically-disordered prion-like domain. Thus, TDP-43 appears to undergo conformational exchanges between "closed" and "open" states which are needed for its functions. Our study thus offers a mechanism by which cellular processes might control TDP-43 physiology and proteinopathy by mediating its inter-domain interactions. PMID:27040765

  4. Trophic cascade facilitates coral recruitment in a marine reserve

    PubMed Central

    Mumby, Peter J.; Harborne, Alastair R.; Williams, Jodene; Kappel, Carrie V.; Brumbaugh, Daniel R.; Micheli, Fiorenza; Holmes, Katherine E.; Dahlgren, Craig P.; Paris, Claire B.; Blackwell, Paul G.

    2007-01-01

    Reduced fishing pressure and weak predator–prey interactions within marine reserves can create trophic cascades that increase the number of grazing fishes and reduce the coverage of macroalgae on coral reefs. Here, we show that the impacts of reserves extend beyond trophic cascades and enhance the process of coral recruitment. Increased fish grazing, primarily driven by reduced fishing, was strongly negatively correlated with macroalgal cover and resulted in a 2-fold increase in the density of coral recruits within a Bahamian reef system. Our conclusions are robust because four alternative hypotheses that may generate a spurious correlation between grazing and coral recruitment were tested and rejected. Grazing appears to influence the density and community structure of coral recruits, but no detectable influence was found on the overall size-frequency distribution, community structure, or cover of corals. We interpret this absence of pattern in the adult coral community as symptomatic of the impact of a recent disturbance event that masks the recovery trajectories of individual reefs. Marine reserves are not a panacea for conservation but can facilitate the recovery of corals from disturbance and may help sustain the biodiversity of organisms that depend on a complex three-dimensional coral habitat. PMID:17488824

  5. Bone overgrowth-associated mutations in the LRP4 gene impair sclerostin facilitator function.

    PubMed

    Leupin, Olivier; Piters, Elke; Halleux, Christine; Hu, Shouih; Kramer, Ina; Morvan, Frederic; Bouwmeester, Tewis; Schirle, Markus; Bueno-Lozano, Manuel; Fuentes, Feliciano J Ramos; Itin, Peter H; Boudin, Eveline; de Freitas, Fenna; Jennes, Karen; Brannetti, Barbara; Charara, Nadine; Ebersbach, Hilmar; Geisse, Sabine; Lu, Chris X; Bauer, Andreas; Van Hul, Wim; Kneissel, Michaela

    2011-06-01

    Humans lacking sclerostin display progressive bone overgrowth due to increased bone formation. Although it is well established that sclerostin is an osteocyte-secreted bone formation inhibitor, the underlying molecular mechanisms are not fully elucidated. We identified in tandem affinity purification proteomics screens LRP4 (low density lipoprotein-related protein 4) as a sclerostin interaction partner. Biochemical assays with recombinant proteins confirmed that sclerostin LRP4 interaction is direct. Interestingly, in vitro overexpression and RNAi-mediated knockdown experiments revealed that LRP4 specifically facilitates the previously described inhibitory action of sclerostin on Wnt1/β-catenin signaling. We found the extracellular β-propeller structured domain of LRP4 to be required for this sclerostin facilitator activity. Immunohistochemistry demonstrated that LRP4 protein is present in human and rodent osteoblasts and osteocytes, both presumed target cells of sclerostin action. Silencing of LRP4 by lentivirus-mediated shRNA delivery blocked sclerostin inhibitory action on in vitro bone mineralization. Notably, we identified two mutations in LRP4 (R1170W and W1186S) in patients suffering from bone overgrowth. We found that these mutations impair LRP4 interaction with sclerostin and its concomitant sclerostin facilitator effect. Together these data indicate that the interaction of sclerostin with LRP4 is required to mediate the inhibitory function of sclerostin on bone formation, thus identifying a novel role for LRP4 in bone.

  6. Characterization of a novel swollenin from Penicillium oxalicum in facilitating enzymatic saccharification of cellulose

    PubMed Central

    2013-01-01

    Background Plant expansins and fungal swollenin that can disrupt crystalline cellulose have great potential for applications in conversion of biomass. Recent studies have been mainly focused on Trichoderma reesei swollenin that show relatively low activity in the promotion of cellulosic hydrolysis. Our aim was to isolate a novel swollenin with greater disruptive activity, to establish an efficient way of producing recombinant swollenin, and to optimize the procedure using swollenin in facilitation of cellulosic hydrolysis. Results A novel gene encoding a swollenin-like protein, POSWOI, was isolated from the filamentous fungus Penicillium oxalicum by Thermal Asymmetric Interlaced PCR (TAIL-PCR). It consisted of a family 1 carbohydrate-binding module (CBM1) followed by a linker connected to a family 45 endoglucanase-like domain. Using the cellobiohydrolase I promoter, recombinant POSWOI was efficiently produced in T. reesei with a yield of 105 mg/L, and showed significant disruptive activity on crystalline cellulose. Simultaneous reaction with both POSWOI and cellulases enhanced the hydrolysis of crystalline cellulose Avicel by approximately 50%. Using a POSWOI-pretreatment procedure, cellulases can produce nearly twice as many reducing sugars as without pretreatment. The mechanism by which POSWOI facilitates the saccharification of cellulose was also studied using a cellulase binding assay. Conclusion We present a novel fungal swollenin with considerable disruptive activity on crystalline cellulose, and develop a better procedure for using swollenin in facilitating cellulosic hydrolysis. We thus provide a new approach for the effective bioconversion of cellulosic biomass. PMID:23688024

  7. Facilitating adverse drug event detection in pharmacovigilance databases using molecular structure similarity: application to rhabdomyolysis

    PubMed Central

    Vilar, Santiago; Harpaz, Rave; Chase, Herbert S; Costanzi, Stefano; Rabadan, Raul

    2011-01-01

    Background Adverse drug events (ADE) cause considerable harm to patients, and consequently their detection is critical for patient safety. The US Food and Drug Administration maintains an adverse event reporting system (AERS) to facilitate the detection of ADE in drugs. Various data mining approaches have been developed that use AERS to detect signals identifying associations between drugs and ADE. The signals must then be monitored further by domain experts, which is a time-consuming task. Objective To develop a new methodology that combines existing data mining algorithms with chemical information by analysis of molecular fingerprints to enhance initial ADE signals generated from AERS, and to provide a decision support mechanism to facilitate the identification of novel adverse events. Results The method achieved a significant improvement in precision in identifying known ADE, and a more than twofold signal enhancement when applied to the ADE rhabdomyolysis. The simplicity of the method assists in highlighting the etiology of the ADE by identifying structurally similar drugs. A set of drugs with strong evidence from both AERS and molecular fingerprint-based modeling is constructed for further analysis. Conclusion The results demonstrate that the proposed methodology could be used as a pharmacovigilance decision support tool to facilitate ADE detection. PMID:21946238

  8. Facilitators and barriers to quality of care in maternal, newborn and child health: a global situational analysis through metareview

    PubMed Central

    Nair, Manisha; Yoshida, Sachiyo; Lambrechts, Thierry; Boschi-Pinto, Cynthia; Bose, Krishna; Mason, Elizabeth Mary; Mathai, Matthews

    2014-01-01

    Objective Conduct a global situational analysis to identify the current facilitators and barriers to improving quality of care (QoC) for pregnant women, newborns and children. Study design Metareview of published and unpublished systematic reviews and meta-analyses conducted between January 2000 and March 2013 in any language. Assessment of Multiple Systematic Reviews (AMSTAR) is used to assess the methodological quality of systematic reviews. Settings Health systems of all countries. Study outcome: QoC measured using surrogate indicators––effective, efficient, accessible, acceptable/patient centred, equitable and safe. Analysis Conducted in two phases (1) qualitative synthesis of extracted data to identify and group the facilitators and barriers to improving QoC, for each of the three population groups, into the six domains of WHO's framework and explore new domains and (2) an analysis grid to map the common facilitators and barriers. Results We included 98 systematic reviews with 110 interventions to improve QoC from countries globally. The facilitators and barriers identified fitted the six domains of WHO's framework––information, patient–population engagement, leadership, regulations and standards, organisational capacity and models of care. Two new domains, ‘communication’ and ‘satisfaction’, were generated. Facilitators included active and regular interpersonal communication between users and providers; respect, confidentiality, comfort and support during care provision; engaging users in decision-making; continuity of care and effective audit and feedback mechanisms. Key barriers identified were language barriers in information and communication; power difference between users and providers; health systems not accounting for user satisfaction; variable standards of implementation of standard guidelines; shortage of resources in health facilities and lack of studies assessing the role of leadership in improving QoC. These were common across

  9. Restoring Tropical Grassland Productivity with Facilitated Biofertilisation

    NASA Astrophysics Data System (ADS)

    Williams, Wendy; Büdel, Burkhard

    2015-04-01

    Grazing is the major economic activity in northern Australia's subtropical grasslands, savannah and shrublands that cover >1.9 million km2 however; there has been significant decline in soil fertility that has led to the need to consider ways to improve management. Terrestrial cyanobacteria primarily inhabit complex soil microbial communities that drive physical and biological processes in the topsoil. These microbes facilitate resilience to drought and maintain soil function. They transform their environment through the secretion of mucilaginous organic compounds that improve aggregate stability, porosity, rainfall infiltration rates and water storage, reduce evaporation and soil erosion and, improve seedling emergence. In the northern Australian savannah cyanobacterial communities dominate soil surfaces of the perennial tussock grasslands. The core focus of this research has been to better understand the function of cyanobacteria within the climate-soil-plant ecosystem. The recent discovery that cyanobacteria are programmed to detect and respond only to wet season rains, and remain inactive and unproductive during the dry season even if it rains, has rewritten our understanding of soil nutrient cycles in the northern Australian savannah. In this project we have established: 1. For the wet season trials (Dec 2009-May 2010) the mean values of cyanobacterial crust (0-1 cm depth; n=100) plant-available N fluctuated, yet significantly increased incrementally from Dec to Feb (2.74 ± 0.37SE-5.62 ± 0.82 mg NH4+ kg-1 soil; p = 0.003) and peaked from Mar-May (9.59 ± 1.5SE-16.04 ± 3.2SE mg NH4+ kg-1 soil; p = 0.127) that represented the concluding stages of the wet season. 2. Cyanobacterial rates of N-fixation (determined by Acetylene Reduction assays, n=6 per month), increased significantly from the commencement to the height of the wet season (13.2 ± 2.9SE-30.2 ± 1.9SE kg N ha-1; p = 0.001) and decreased towards the end of the wet season (10.4 ± 1.8SE kg N ha-1; p

  10. Flying blind: the experience of online interprofessional facilitation.

    PubMed

    Hanna, Elizabeth; Soren, Barbara; Telner, Deanna; MacNeill, Heather; Lowe, Mandy; Reeves, Scott

    2013-07-01

    The role of the facilitator is known to be important in fostering productive interprofessional education (IPE) in the face-to-face (F2F) environment. Online learning can help surmount some of the logistical challenges in IPE by bringing together diverse professionals in multiple geographical locations. Best practices in F2F IPE facilitation are beginning to emerge, but there is scant literature examining IPE facilitation online. What little research exists has focused on the asynchronous environment and suggests that the skill sets of online and F2F facilitators have considerable overlap, but there are further demands in the online setting. This qualitative study sought to examine online synchronous IPE facilitation through the self-reported experiences of seven trained facilitators during a 12-week online course. Data collected through focus groups and targeted interviews were analyzed by the research team using constant comparison techniques. Four major themes were revealed: technology as a dynamic force, reduction in non-verbal cues, evolution of the online IPE group process over time and the importance of co-facilitation. The foundations of IPE facilitation were seen to carry over to the online setting. This study has implications for the training of IPE facilitators and for the design of online IPE learning experiences. PMID:23002787

  11. Branch-specific heterosynaptic facilitation in Aplysia siphon sensory cells.

    PubMed

    Clark, G A; Kandel, E R

    1984-04-01

    Aplysia siphon sensory cells exhibit heterosynaptic facilitation of transmitter release during both sensitization and classical conditioning of the siphon withdrawal response. In the present study, we asked whether facilitation must invariably enhance transmission at all terminals of a neuron or whether facilitation can instead occur at one set of terminals without also occurring at other terminals of the same cell. To examine this question, we compared effects of local application of serotonin and of connective stimulation on transmission at central and peripheral branches of single sensory cells. We found that heterosynaptic facilitation can be branch-specific and can occur at either central or peripheral synapses independently. We also found that siphon sensory cells exhibit homosynaptic post-tetanic potentiation, allowing us to compare effects of hetero- and homosynaptic facilitation in the same cells. By contrast to heterosynaptic facilitation, homosynaptic facilitation occurs concomitantly at both central and peripheral synapses of siphon sensory cells. Thus, while both heterosynaptic and homosynaptic facilitation involve increases in transmitter release from sensory neuron terminals, heterosynaptic facilitation provides a greater specificity and flexibility in the modification of synaptic connections.

  12. Changes in nociceptive reflex facilitation during carrageenan-induced arthritis.

    PubMed

    Herrero, J F; Cervero, F

    1996-04-22

    Facilitation of neuronal responses induced by repetitive electrical stimulation of C-fibres (wind-up) is thought to be a substrate of hyperalgesia. There is little information on how these responses are in turn modified during hyperalgesia, and the extent to which hyperalgesic states also induce a facilitation of the neuronal responses mediated by A-fibres. The current study was undertaken in order to evaluate the effects of peripheral inflammation and stimulus presentation on the facilitation of nociceptive reflexes. Flexor reflexes, recorded as single motor units, were evoked in rats by cycles of low and high frequency electrical stimulation with pulse durations of 0.2, 0.5 and 2 ms. Responses were studied in control and inflammatory conditions, using the carrageenan-induced mono-arthritis model. The results show that the facilitation of late (C-fibre mediated) responses was proportional to the pulse duration of stimulation, as well as to the stimulation frequency. Facilitation was always higher when animals were subjected to inflammation. In inflammatory conditions, facilitation of reflexes was observed not only for late (C-fibre mediated) but also for early (A-fibre mediated) reflex responses. However, the facilitation of these early responses was not proportional to the intensity of stimulation. Thus, in arthritic animals, late (C-fibre mediated) flexion reflexes elicited from the skin, are facilitated and early (A-fibre mediated) reflexes are not only facilitated but, in addition, show a novel wind-up phenomenon.

  13. 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.

  14. Barriers and Facilitators for Generalizing Cycling Skills Learned at Camp to Home.

    PubMed

    Temple, Viviene A; Purves, P Lynn; Misovic, Robyn; Lewis, Coral J; DeBoer, Carrie

    2016-01-01

    Many children with disabling conditions do not acquire the skills to successfully ride a 2-wheeled bicycle. The aim was to describe cycling patterns before and after an innovative learn-to-ride bike camp and factors that facilitate or hinder the generalization of skills developed at camp to home. Parents and children participated in semistructured interviews 3-4 mo postcamp. Transcripts were examined deductively for participation and contextual influences using a template of codes approach. None of the children were successfully riding a 2-wheeled bicycle before camp. Two patterns of participation were evident from narrative descriptions of postcamp riding: "riders" and "not there yet." Major facilitating factors were the camp itself, the interaction between the camp and the health service, and continued parent involvement. The program transferred well to home for children who were riding independently on the last day of camp. Ongoing support is needed for children "not there yet."

  15. 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

  16. Vertebrate intersectin1 is repurposed to facilitate cortical midline connectivity and higher order cognition.

    PubMed

    Sengar, Ameet S; Ellegood, Jacob; Yiu, Adelaide P; Wang, Hua; Wang, Wei; Juneja, Subhash C; Lerch, Jason P; Josselyn, Sheena A; Henkelman, R Mark; Salter, Michael W; Egan, Sean E

    2013-02-27

    Invertebrate studies have highlighted a role for EH and SH3 domain Intersectin (Itsn) proteins in synaptic vesicle recycling and morphology. Mammals have two Itsn genes (Itsn1 and Itsn2), both of which can undergo alternative splicing to include DBL/PH and C2 domains not present in invertebrate Itsn proteins. To probe for specific and redundant functions of vertebrate Itsn genes, we generated Itsn1, Itsn2, and double mutant mice. While invertebrate mutants showed severe synaptic abnormalities, basal synaptic transmission and plasticity were unaffected at Schaffer CA1 synapses in mutant mice. Surprisingly, intercortical tracts-corpus callosum, ventral hippocampal, and anterior commissures-failed to cross the midline in mice lacking Itsn1, but not Itsn2. In contrast, tracts extending within hemispheres and those that decussate to more caudal brain segments appeared normal. Itsn1 mutant mice showed severe deficits in Morris water maze and contextual fear memory tasks, whereas mice lacking Itsn2 showed normal learning and memory. Thus, coincident with the acquisition of additional signaling domains, vertebrate Itsn1 has been functionally repurposed to also facilitate interhemispheric connectivity essential for high order cognitive functions.

  17. Functional independence in resting-state connectivity facilitates higher-order cognition.

    PubMed

    James, G Andrew; Kearney-Ramos, Tonisha E; Young, Jonathan A; Kilts, Clinton D; Gess, Jennifer L; Fausett, Jennifer S

    2016-06-01

    Growing evidence suggests that intrinsic functional connectivity (i.e. highly structured patterns of communication between brain regions during wakeful rest) may encode cognitive ability. However, the generalizability of these findings is limited by between-study differences in statistical methodology and cognitive domains evaluated. To address this barrier, we evaluated resting-state neural representations of multiple cognitive domains within a relatively large normative adult sample. Forty-four participants (mean(sd) age=31(10) years; 18 male and 26 female) completed a resting-state functional MRI scan and neuropsychological assessments spanning motor, visuospatial, language, learning, memory, attention, working memory, and executive function performance. Robust linear regression related cognitive performance to resting-state connectivity among 200 a priori determined functional regions of interest (ROIs). Only higher-order cognitions (such as learning and executive function) demonstrated significant relationships between brain function and behavior. Additionally, all significant relationships were negative - characterized by moderately positive correlations among low performers and weak to moderately negative correlations among high performers. These findings suggest that functional independence among brain regions at rest facilitates cognitive performance. Our interpretation is consistent with graph theoretic analyses which represent the brain as independent functional nodes that undergo dynamic reorganization with task demand. Future work will build upon these findings by evaluating domain-specific variance in resting-state neural representations of cognitive impairment among patient populations.

  18. Functional independence in resting-state connectivity facilitates higher-order cognition.

    PubMed

    James, G Andrew; Kearney-Ramos, Tonisha E; Young, Jonathan A; Kilts, Clinton D; Gess, Jennifer L; Fausett, Jennifer S

    2016-06-01

    Growing evidence suggests that intrinsic functional connectivity (i.e. highly structured patterns of communication between brain regions during wakeful rest) may encode cognitive ability. However, the generalizability of these findings is limited by between-study differences in statistical methodology and cognitive domains evaluated. To address this barrier, we evaluated resting-state neural representations of multiple cognitive domains within a relatively large normative adult sample. Forty-four participants (mean(sd) age=31(10) years; 18 male and 26 female) completed a resting-state functional MRI scan and neuropsychological assessments spanning motor, visuospatial, language, learning, memory, attention, working memory, and executive function performance. Robust linear regression related cognitive performance to resting-state connectivity among 200 a priori determined functional regions of interest (ROIs). Only higher-order cognitions (such as learning and executive function) demonstrated significant relationships between brain function and behavior. Additionally, all significant relationships were negative - characterized by moderately positive correlations among low performers and weak to moderately negative correlations among high performers. These findings suggest that functional independence among brain regions at rest facilitates cognitive performance. Our interpretation is consistent with graph theoretic analyses which represent the brain as independent functional nodes that undergo dynamic reorganization with task demand. Future work will build upon these findings by evaluating domain-specific variance in resting-state neural representations of cognitive impairment among patient populations. PMID:27105037

  19. Knowledge Discovery from Biomedical Ontologies in Cross Domains.

    PubMed

    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.

  20. 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

  1. Knowledge Discovery from Biomedical Ontologies in Cross Domains.

    PubMed

    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

  2. The structural mechanism of KCNH-channel regulation by the eag domain

    PubMed Central

    Haitin, Yoni; Carlson, Anne E.; Zagotta, William N.

    2013-01-01

    The KCNH voltage-dependent potassium channels (ether-á-go-go, EAG; EAG-related gene, ERG; EAG-like channels, ELK) are important regulators of cellular excitability1-3 and have key roles in diseases such as cardiac long QT syndrome type 2 (LQT2)4, epilepsy5, schizophrenia6 and cancer7. The intracellular domains of KCNH channels are structurally distinct from other voltage-gated channels. The amino-terminal region contains an eag domain, which is comprised of a Per-Arnt-Sim (PAS) domain and a PAS-cap domain8, while the carboxy-terminal region contains a cyclic nucleotide-binding homology domain (CNBHD) which is connected to the pore through a C-linker domain. Many disease-causing mutations localize to these specialized intracellular domains, which underlie the unique gating and regulation of KCNH channels9. It has been suggested that the eag domain may regulate the channel by interacting with either the S4-S5 linker or the CNBHD8,10. Here we present a 2-Å resolution crystal structure of the eag domain-CNBHD complex of the mouse EAG1 (mEAG1) channel. It displays extensive interactions between the eag domain and the CNBHD, indicating that the regulatory mechanism of the eag domain involves primarily the CNBHD. Surprisingly, the structure reveals that a number of LQT2 mutations at homologous positions in hERG, and cancer-associated mutations in EAG channels, localize to the eag domain-CNBHD interface. Furthermore, mutations at the interface produced dramatic effects on channel gating demonstrating the important physiological role of the eag domain-CNBHD interaction. Our structure of the eag domain-CNBHD complex of mEAG1 provides unique insights into the physiological and pathophysiological mechanisms of KCNH channels. PMID:23975098

  3. Do mirrors facilitate acquisition of motor imitation in children diagnosed with autism?

    PubMed

    Miller, Scott A; Rodriguez, Nicole M; Rourke, Ami J

    2015-01-01

    We evaluated the efficacy of a procedure that incorporated a mirror to teach gross motor imitation with a 2-year-old boy who had been diagnosed with autistic disorder. Responses taught with a mirror were acquired more quickly than responses taught without the mirror and were maintained after the mirror was removed. These data indicate that a mirror can facilitate acquisition of motor imitation. PMID:25684255

  4. 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.

  5. 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.

  6. 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

  7. 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...

  8. Frequency domain photoacoustic and fluorescence microscopy.

    PubMed

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

    2016-07-01

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

  9. Frequency domain photoacoustic and fluorescence microscopy.

    PubMed

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

    2016-07-01

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

  10. 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

  11. 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...

  12. 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.…

  13. 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…

  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 Making it…

  15. Neurophysiological Facilitation of Eating Skills in Children with Severe Handicaps.

    ERIC Educational Resources Information Center

    Sobsey, Richard; Orelove, Fred P.

    1984-01-01

    Effectiveness of neurophysiological facilitation procedures (exteroceptive and proprioceptive stimulation) was evaluated on lip closure, rotary chewing, and food spilling from the mouth of four severely disabled children (3-12 years old). Some improvements in eating skills were found in each student following facilitation procedures. (CL)

  16. 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…

  17. 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...

  18. 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…

  19. 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…

  20. 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.

  1. 50 CFR 300.118 - Facilitation of enforcement and inspection.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 7 2010-10-01 2010-10-01 false Facilitation of enforcement and inspection. 300.118 Section 300.118 Wildlife and Fisheries INTERNATIONAL FISHING AND RELATED ACTIVITIES INTERNATIONAL FISHERIES REGULATIONS Antarctic Marine Living Resources § 300.118 Facilitation of enforcement...

  2. 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…

  3. A Study of Self-Actualization and Facilitative Communication.

    ERIC Educational Resources Information Center

    Omizo, Michael M.

    1981-01-01

    Examined the relationship between self-actualization measures and ability in facilitative communication of trainees from counseling, social work, and psychology programs to determine if differences existed between the three groups. Self-actualization indexes were significantly correlated with ability in facilitative communication. (RC)

  4. 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…

  5. 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…

  6. Ten Great Tips for Facilitating Virtual Learning Teams.

    ERIC Educational Resources Information Center

    Bailey, Margaret L.; Luetkehans, Lara

    This paper presents tips for educators to integrate and facilitate virtual learning teams within online courses. The techniques are grounded in current research and theoretical foundations of systems theory and group dynamics. Tips emphasize facilitation of virtual learning teams, assembled for the purpose of formal education and supported by…

  7. Student-Facilitators' Roles in Moderating Online Discussions

    ERIC Educational Resources Information Center

    Wang, Qiyun

    2008-01-01

    Intellectual, social, managerial and technical are four commonly reported categories of facilitation in online discussions. The purpose of this study was to investigate whether these four broad categories of facilitation were equally applied in online discussions and which specific skills were perceived to be more important. In this study,…

  8. A STUDY OF SOCIAL FACILITATION DURING PROGRAMMED INSTRUCTION. FINAL REPORT.

    ERIC Educational Resources Information Center

    KRESS, GERARD C., JR.

    THIS STUDY INVESTIGATES THE POTENTIALLY FACILITATIVE AND INHIBITORY EFFECTS OF SOCIAL INTERACTION DURING PROGRAMED INSTRUCTION. SPECIFIC OBJECTIVES WERE (1) TO IDENTIFY THE PARTICULAR ASPECTS OF SOCIAL INTERACTION CRITICAL TO FACILITATING OR INHIBITING PROGRAMED LEARNING, AND (2) TO DETERMINE THE METHOD OF CONSTRUCTING WORK GROUPS THAT OPTIMIZES…

  9. 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…

  10. 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…

  11. Facilitating Action Research for Curriculum Development in Higher Education.

    ERIC Educational Resources Information Center

    Burchell, Helen

    2000-01-01

    Examines the role of a facilitator in an action research project, and explores the dilemmas it presents. Focuses on development of a competence-based approach to the clinical education and assessment of student radiographers. Concludes that the facilitator must understand the nature of each dilemma and make a judgment regarding how to work with it…

  12. 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,…

  13. Direct observation of ferroelectric domain switching in varying electric field regimes using in situ TEM.

    PubMed

    Winkler, C R; Damodaran, A R; Karthik, J; Martin, L W; Taheri, M L

    2012-11-01

    In situ Transmission Electron Microscopy (TEM) techniques can potentially fill in gaps in the current understanding interfacial phenomena in complex oxides. Select multiferroic oxide materials, such as BiFeO(3) (BFO), exhibit ferroelectric and magnetic order, and the two order parameters are coupled through a quantum-mechanical exchange interaction. The magneto-electric coupling in BFO allows control of the ferroelectric and magnetic domain structures via applied electric fields. Because of these unique properties, BFO and other magneto-electric multiferroics constitute a promising class of materials for incorporation into devices such as high-density ferroelectric and magnetoresistive memories, spin valves, and magnetic field sensors. The magneto-electric coupling in BFO is mediated by volatile ferroelastically switched domains that make it difficult to incorporate this material into devices. To facilitate device integration, an understanding of the microstructural factors that affect ferroelastic relaxation and ferroelectric domain switching must be developed. In this article, a method of viewing ferroelectric (and ferroelastic) domain dynamics using in situ biasing in TEM is presented. The evolution of ferroelastically switched ferroelectric domains in BFO thin films during many switching cycles is investigated. Evidence of partial domain nucleation, propagation, and switching even at applied electric fields below the estimated coercive field is revealed. Our observations indicate that the occurrence of ferroelastic relaxation in switched domains and the stability of these domains is influenced the applied field as well as the BFO microstructure. These biasing experiments provide a real time view of the complex dynamics of domain switching and complement scanning probe techniques. Quantitative information about domain switching under bias in ferroelectric and multiferroic materials can be extracted from in situ TEM to provide a predictive tool for future device

  14. Characterization of cholesterol-sphingomyelin domains and their dynamics in bilayer membranes.

    PubMed Central

    Samsonov, A V; Mihalyov, I; Cohen, F S

    2001-01-01

    Lipids segregate with each other into small domains in biological membranes, which can facilitate the associations of particular proteins. The segregation of cholesterol and sphingomyelin (SPM) into domains known as rafts is thought to be especially important. The formation of rafts was studied by using planar bilayer membranes that contained rhodamine-phosphatidylethanolamine (rho-DOPE) as a fluorescent probe, and wide-field fluorescence microscopy was used to detect phase separation of the probe. A fluorescently labeled GM(1), known to preferentially partition into rafts, verified that rho-DOPE faithfully reported the rafts. SPM-cholesterol domains did not form at high temperatures but spontaneously formed when temperature was lowered to below the melting temperature of the SPM. Saturated acyl chains on SPMs therefore promote the formation of rafts. The domains were circular (resolution > or = 0.5 microm), quickly reassumed their circular shape after they were deformed, and merged with each other to create larger domains, all phenomena consistent with liquid-ordered (l(o)) rather than solid-ordered (s(o)) domains. A saturated phosphatidylcholine (PC), disteoryl-PC, could substitute for SPM to complex with cholesterol into a l(o)-domain. But in the presence of cholesterol, a saturated phosphatidylethanolamine or phosphatidylserine yielded s(o)-domains of irregular shape. Lipids with saturated acyl chains can therefore pack well among each other and with cholesterol to form l(o)-domains, but domain formation is dependent on the polar headgroup of the lipid. An individual raft always extended through both monolayers. Degrading cholesterol in one monolayer with cholesterol oxidase first caused the boundary of the raft to become irregular; then the raft gradually disappeared. The fluid nature of rafts, demonstrated in this study, may be important for permitting dynamic interactions between proteins localized within rafts. PMID:11509362

  15. 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

  16. Facilitating memory with hypnosis, focused meditation, and eye closure.

    PubMed

    Wagstaff, Graham F; Brunas-Wagstaff, Jo; Cole, Jon; Knapton, Luke; Winterbottom, James; Crean, Vicki; Wheatcroft, Jacqueline

    2004-10-01

    Three experiments examined some features of hypnotic induction that might be useful in the development of brief memory-facilitation procedures. The first involved a hypnosis procedure designed to facilitate face identification; the second employed a brief, focused-meditation (FM) procedure, with and without eye closure, designed to facilitate memory for an emotional event. The third experiment was a check for simple motivation and expectancy effects. Limited facilitation effects were found for hypnosis, but these were accompanied by increased confidence in incorrect responses. However, eye closure and FM were effective in facilitating free recall of an event without an increase in errors. FM reduced phonemic fluency, suggesting that the effectiveness of FM was not due to simple changes in expectancy or motivation.

  17. Evaluating facilitated communications of people with developmental disabilities.

    PubMed

    Szempruch, J; Jacobson, J W

    1993-01-01

    A quasi-experimental message-passing procedure was used to assess the validity of the facilitated communication (FC) by people with autism and mental retardation or with mental retardation. The 23 participants were classified as having intellectual skills within the range of severe to profound mental retardation. Message-passing consisted of showing and verbally labeling a picture of a familiar object with the facilitator absent, and subsequent facilitation to generate a label or description of the object. Three-trial blocks were conducted with each participant on two different days. Blocks were conducted in the participants' normal FC setting, with their facilitators of choice, and no special apparatus was used. No participant was able to accurately label or describe the object shown to them with facilitation. Possible reasons for findings set forth by proponents of FC and findings from the emerging quantitative literature on FC are considered. PMID:8210603

  18. One Health Core Competency Domains.

    PubMed

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

    2016-01-01

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

  19. 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

  20. 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.

  1. One Health Core Competency Domains.

    PubMed

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

    2016-01-01

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

  2. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2008-11-01

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

  4. 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.

  5. Domain wall conduction in multiaxial ferroelectrics

    SciTech Connect

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

    2012-01-01

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

  6. Identification, modeling, and characterization studies of Tetrahymena thermophila myosin FERM domains suggests a conserved core fold but functional differences.

    PubMed

    Martin, Che L; Singh, Shaneen M

    2015-11-01

    Myosins (MYO) define a superfamily of motor proteins which facilitate movement along cytoskeletal actin filaments in an ATP-dependent manner. To date, over 30 classes of myosin have been defined that vary in their roles and distribution across different taxa. The multidomain tail of myosin is responsible for the observed functional differences in different myosin classes facilitating differential binding to different cargos. One domain found in this region, the FERM domain, is found in several diverse proteins and is involved in many biological functions ranging from cell adhesion and actin-driven cytoskeleton assembly to cell signaling. Recently, new classes of unconventional myosin have been identified in Tetrahymena thermophila. In this study, we have identified, modeled, and characterized eight FERM domains from the unconventional T. thermophila myosins as their complete functional MyTH4-FERM cassettes. Our results reveal notable sequence, structural, and electrostatic differences between T. thermophila and other characterized FERM domains. Specifically, T. thermophila FERM domains contain helical inserts or extensions, which contribute to significant differences in surface electrostatic profiles of T. thermophila myosin FERMs when compared to the conventional FERM domains. Analyses of the modeled domains reveal differences in key functional residues as well as phosphoinositide-binding signatures and affinities. The work presented here broadens the scope of our understanding of myosin classes and their inherent functions, and provides a platform for experimentalists to design rational experimental studies to test the functional roles for T. thermophila myosins. PMID:26492945

  7. Identification, modeling, and characterization studies of Tetrahymena thermophila myosin FERM domains suggests a conserved core fold but functional differences.

    PubMed

    Martin, Che L; Singh, Shaneen M

    2015-11-01

    Myosins (MYO) define a superfamily of motor proteins which facilitate movement along cytoskeletal actin filaments in an ATP-dependent manner. To date, over 30 classes of myosin have been defined that vary in their roles and distribution across different taxa. The multidomain tail of myosin is responsible for the observed functional differences in different myosin classes facilitating differential binding to different cargos. One domain found in this region, the FERM domain, is found in several diverse proteins and is involved in many biological functions ranging from cell adhesion and actin-driven cytoskeleton assembly to cell signaling. Recently, new classes of unconventional myosin have been identified in Tetrahymena thermophila. In this study, we have identified, modeled, and characterized eight FERM domains from the unconventional T. thermophila myosins as their complete functional MyTH4-FERM cassettes. Our results reveal notable sequence, structural, and electrostatic differences between T. thermophila and other characterized FERM domains. Specifically, T. thermophila FERM domains contain helical inserts or extensions, which contribute to significant differences in surface electrostatic profiles of T. thermophila myosin FERMs when compared to the conventional FERM domains. Analyses of the modeled domains reveal differences in key functional residues as well as phosphoinositide-binding signatures and affinities. The work presented here broadens the scope of our understanding of myosin classes and their inherent functions, and provides a platform for experimentalists to design rational experimental studies to test the functional roles for T. thermophila myosins.

  8. 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.

  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. 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.

  11. Piezoelectric Enhancement of (PbTiO3)m/(BaTiO3)n Ferroelectric Superlattices through Domain Engineering

    SciTech Connect

    Hong, Liang; Wu, Pingping; Li, Yulan; Gopalan, Venkatraman; Eom, C.B.; Schlom, Darrell G.; Chen, Long-Qing

    2014-11-20

    The phase diagram of (PbTiO3)m/(BaTiO3)n ferroelectric superlattices was computed using the phase-field approach as a function of layer volume fraction and biaxial strain to tune ferroelectric properties through domain engineering. Two interesting domain structures are found: one with mixed Bloch-Néel-Ising domain wall structures and the other with stabilized monoclinic phases. The polarization of the monoclinic phase is able to rotate from out-of-plane to in-plane or vice versa under an electric field, and thus facilitates the domain reversal of rhombohedral domains. This contributes significantly to both reduced coercive fields and enhanced piezoelectric responses.

  12. The Tetramerization Domain Potentiates Kv4 Channel Function by Suppressing Closed-State Inactivation

    PubMed Central

    Tang, Yi-Quan; Zhou, Jing-Heng; Yang, Fan; Zheng, Jie; Wang, KeWei

    2014-01-01

    A-type Kv4 potassium channels undergo a conformational change toward a nonconductive state at negative membrane potentials, a dynamic process known as pre-open closed states or closed-state inactivation (CSI). CSI causes inhibition of channel activity without the prerequisite of channel opening, thus providing a dynamic regulation of neuronal excitability, dendritic signal integration, and synaptic plasticity at resting. However, the structural determinants underlying Kv4 CSI remain largely unknown. We recently showed that the auxiliary KChIP4a subunit contains an N-terminal Kv4 inhibitory domain (KID) that directly interacts with Kv4.3 channels to enhance CSI. In this study, we utilized the KChIP4a KID to probe key structural elements underlying Kv4 CSI. Using fluorescence resonance energy transfer two-hybrid mapping and bimolecular fluorescence complementation-based screening combined with electrophysiology, we identified the intracellular tetramerization (T1) domain that functions to suppress CSI and serves as a receptor for the binding of KID. Disrupting the Kv4.3 T1-T1 interaction interface by mutating C110A within the C3H1 motif of T1 domain facilitated CSI and ablated the KID-mediated enhancement of CSI. Furthermore, replacing the Kv4.3 T1 domain with the T1 domain from Kv1.4 (without the C3H1 motif) or Kv2.1 (with the C3H1 motif) resulted in channels functioning with enhanced or suppressed CSI, respectively. Taken together, our findings reveal a novel (to our knowledge) role of the T1 domain in suppressing Kv4 CSI, and that KChIP4a KID directly interacts with the T1 domain to facilitate Kv4.3 CSI, thus leading to inhibition of channel function. PMID:25185545

  13. Temperature-induced changes of HtrA2(Omi) protease activity and structure.

    PubMed

    Zurawa-Janicka, Dorota; Jarzab, Miroslaw; Polit, Agnieszka; Skorko-Glonek, Joanna; Lesner, Adam; Gitlin, Agata; Gieldon, Artur; Ciarkowski, Jerzy; Glaza, Przemyslaw; Lubomska, Agnieszka; Lipinska, Barbara

    2013-01-01

    HtrA2(Omi), belonging to the high-temperature requirement A (HtrA) family of stress proteins, is involved in the maintenance of mitochondrial homeostasis and in the stimulation of apoptosis, as well as in cancer and neurodegenerative disorders. The protein comprises a serine protease domain and a postsynaptic density of 95 kDa, disk large, and zonula occludens 1 (PDZ) regulatory domain and functions both as a protease and a chaperone. Based on the crystal structure of the HtrA2 inactive trimer, it has been proposed that PDZ domains restrict substrate access to the protease domain and that during protease activation there is a significant conformational change at the PDZ-protease interface, which removes the inhibitory effect of PDZ from the active site. The crystal structure of the HtrA2 active form is not available yet. HtrA2 activity markedly increases with temperature. To understand the molecular basis of this increase in activity, we monitored the temperature-induced structural changes using a set of single-Trp HtrA2 mutants with Trps located at the PDZ-protease interface. The accessibility of each Trp to aqueous medium was assessed by fluorescence quenching, and these results, in combination with mean fluorescence lifetimes and wavelength emission maxima, indicate that upon an increase in temperature the HtrA2 structure relaxes, the PDZ-protease interface becomes more exposed to the solvent, and significant conformational changes involving both domains occur at and above 30 °C. This conclusion correlates well with temperature-dependent changes of HtrA2 proteolytic activity and the effect of amino acid substitutions (V226K and R432L) located at the domain interface, on HtrA2 activity. Our results experimentally support the model of HtrA2 activation and provide an insight into the mechanism of temperature-induced changes in HtrA2 structure.

  14. The propagation of self-control: Self-control in one domain simultaneously improves self-control in other domains.

    PubMed

    Tuk, Mirjam A; Zhang, Kuangjie; Sweldens, Steven

    2015-06-01

    [Correction Notice: An Erratum for this article was reported in Vol 144(3) of Journal of Experimental Psychology: General (see record 2015-24174-008). The affiliations for co-authors Kuangjie Zhang and Steven Sweldens were incorrect. All versions of this article have been corrected.] A rich tradition in self-control research has documented the negative consequences of exerting self-control in 1 task for self-control performance in subsequent tasks. However, there is a dearth of research examining what happens when people exert self-control in multiple domains simultaneously. The current research aims to fill this gap. We integrate predictions from the most prominent models of self-control with recent neuropsychological insights in the human inhibition system to generate the novel hypothesis that exerting effortful self-control in 1 task can simultaneously improve self-control in completely unrelated domains. An internal meta-analysis on all 18 studies we conducted shows that exerting self-control in 1 domain (i.e., controlling attention, food consumption, emotions, or thoughts) simultaneously improves self-control in a range of other domains, as demonstrated by, for example, reduced unhealthy food consumption, better Stroop task performance, and less impulsive decision making. A subset of 9 studies demonstrates the crucial nature of task timing-when the same tasks are executed sequentially, our results suggest the emergence of an ego depletion effect. We provide conservative estimates of the self-control facilitation (d = |0.22|) as well as the ego depletion effect size (d = |0.17|) free of data selection and publication biases. These results (a) shed new light on self-control theories, (b) confirm recent claims that previous estimates of the ego depletion effect size were inflated due to publication bias, and (c) provide a blueprint for how to handle the power issues and associated file drawer problems commonly encountered in multistudy research projects. PMID

  15. The propagation of self-control: Self-control in one domain simultaneously improves self-control in other domains.

    PubMed

    Tuk, Mirjam A; Zhang, Kuangjie; Sweldens, Steven

    2015-06-01

    [Correction Notice: An Erratum for this article was reported in Vol 144(3) of Journal of Experimental Psychology: General (see record 2015-24174-008). The affiliations for co-authors Kuangjie Zhang and Steven Sweldens were incorrect. All versions of this article have been corrected.] A rich tradition in self-control research has documented the negative consequences of exerting self-control in 1 task for self-control performance in subsequent tasks. However, there is a dearth of research examining what happens when people exert self-control in multiple domains simultaneously. The current research aims to fill this gap. We integrate predictions from the most prominent models of self-control with recent neuropsychological insights in the human inhibition system to generate the novel hypothesis that exerting effortful self-control in 1 task can simultaneously improve self-control in completely unrelated domains. An internal meta-analysis on all 18 studies we conducted shows that exerting self-control in 1 domain (i.e., controlling attention, food consumption, emotions, or thoughts) simultaneously improves self-control in a range of other domains, as demonstrated by, for example, reduced unhealthy food consumption, better Stroop task performance, and less impulsive decision making. A subset of 9 studies demonstrates the crucial nature of task timing-when the same tasks are executed sequentially, our results suggest the emergence of an ego depletion effect. We provide conservative estimates of the self-control facilitation (d = |0.22|) as well as the ego depletion effect size (d = |0.17|) free of data selection and publication biases. These results (a) shed new light on self-control theories, (b) confirm recent claims that previous estimates of the ego depletion effect size were inflated due to publication bias, and (c) provide a blueprint for how to handle the power issues and associated file drawer problems commonly encountered in multistudy research projects.

  16. Feasibility and Domain Validation of RA Flare Core Domain Set: A Report of the OMERACT 2014 RA Flare Group Plenary

    PubMed Central

    Bartlett, Susan J.; Bykerk, Vivian P.; Cooksey, Roxanne; Choy, Ernest H.; Alten, Rieke; Christensen, Robin; Furst, Daniel E.; Guillemin, Francis; Halls, Serena; Hewlett, Sarah; Leong, Amye L.; Lyddiatt, Anne; March, Lyn; Montie, Pamela; Orbai, Ana Maria; Pohl, Christoph; Voshaar, Marieke Scholte; Woodworth, Thasia G.; Bingham, Clifton O.

    2015-01-01

    Objective The OMERACT RA Flare Group was established to develop an approach to identify and measure rheumatoid arthritis (RA) flares. Here, we provide an overview of our OMERACT 2014 plenary. Methods Feasibility and validity of flare domains endorsed at OMERACT 11 (2012) were described based on initial data from three international studies collected using a common set of questions specific to RA flare. Mean flare frequency, severity, and duration data were presented, and domain scores were compared by flare status to examine known-groups validity. Breakout groups provided input for stiffness, self-management, contextual factors, and measurement considerations. Results Flare data from 501 patients in a observational study indicated 39% were in a flare, with mean (SD) severity of 6.0 (2.6) and 55% lasting > 14 days. Pain, physical function, fatigue, participation and stiffness scores averaged ≥ 2 times higher (2 of 11 points) in flaring individuals. Correlations between flare domains and corresponding legacy instruments were r’s from 0.46 to 0.93. A combined definition (patient-report of flare and DAS28 increase) was evaluated in two other trials with similar results. Breakout groups debated specific measurement issues. Conclusion These data contribute initial evidence of feasibility and content validation of the OMERACT RA Flare Core Domain Set. Our research agenda for OMERACT 2016 includes establishing duration/intensity criteria and developing criteria to identify RA flares using existing disease activity measures. Ongoing work will also address discordance between patients and physician ratings, facilitate applications to clinical care, elucidate the role of self-management and help finalize recommendations for RA flare measurement. PMID:25684764

  17. 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…

  18. Structural Insights into a Wildtype Domain of the Oncoprotein E6 and Its Interaction with a PDZ Domain

    PubMed Central

    Mischo, André; Ohlenschläger, Oliver; Hortschansky, Peter; Ramachandran, Ramadurai; Görlach, Matthias

    2013-01-01

    The high-risk human papilloma virus (HPV) oncoproteins E6 and E7 interact with key cellular regulators and are etiological agents for tumorigenesis and tumor maintenance in cervical cancer and other malignant conditions. E6 induces degradation of the tumor suppressor p53, activates telomerase and deregulates cell polarity. Analysis of E6 derived from a number of high risk HPV finally yielded the first structure of a wild-type HPV E6 domain (PDB 2M3L) representing the second zinc-binding domain of HPV 51 E6 (termed 51Z2) determined by NMR spectroscopy. The 51Z2 structure provides clues about HPV-type specific structural differences between E6 proteins. The observed temperature sensitivity of the well-folded wild-type E6 domain implies a significant malleability of the oncoprotein in vivo. Hence, the structural differences between individual E6 and their malleability appear, together with HPV type-specific surface exposed side-chains, to provide the structural basis for the different interaction networks reported for individual E6 proteins. Furthermore, the interaction of 51Z2 with a PDZ domain of hDlg was analyzed. Human Dlg constitutes a prototypic representative of the large family of PDZ proteins regulating cell polarity, which are common targets of high-risk HPV E6. Nine C-terminal residues of 51Z2 interact with the second PDZ domain of hDlg2. Surface plasmon resonance in conjunction with the NMR spectroscopy derived complex structure (PDB 2M3M) indicate that E6 residues N-terminal to the canonical PDZ-BM of E6 significantly contribute to this interaction and increase affinity. The structure of the complex reveals how residues outside of the classical PDZ-BM enhance the affinity of E6 towards PDZ domains. Such mechanism facilitates successful competition of E6 with cellular PDZ-binding proteins and may apply to PDZ-binding proteins of other viruses as well. PMID:23638119

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

    PubMed

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

    2011-06-01

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

  20. Vesicle uncoating regulated by SH3-SH3 domain-mediated complex formation between endophilin and intersectin at synapses

    PubMed Central

    Pechstein, Arndt; Gerth, Fabian; Milosevic, Ira; Jäpel, Maria; Eichhorn-Grünig, Marielle; Vorontsova, Olga; Bacetic, Jelena; Maritzen, Tanja; Shupliakov, Oleg; Freund, Christian; Haucke, Volker

    2015-01-01

    Neurotransmission involves the exo-endocytic cycling of synaptic vesicle (SV) membranes. Endocytic membrane retrieval and clathrin-mediated SV reformation require curvature-sensing and membrane-bending BAR domain proteins such as endophilin A. While their ability to sense and stabilize curved membranes facilitates membrane recruitment of BAR domain proteins, the precise mechanisms by which they are targeted to specific sites of SV recycling has remained unclear. Here, we demonstrate that the multi-domain scaffold intersectin 1 directly associates with endophilin A to facilitate vesicle uncoating at synapses. Knockout mice deficient in intersectin 1 accumulate clathrin-coated vesicles at synapses, a phenotype akin to loss of endophilin function. Intersectin 1/endophilin A1 complex formation is mediated by direct binding of the SH3B domain of intersectin to a non-canonical site on the SH3 domain of endophilin A1. Consistent with this, intersectin-binding defective mutant endophilin A1 fails to rescue clathrin accumulation at neuronal synapses derived from endophilin A1-3 triple knockout (TKO) mice. Our data support a model in which intersectin aids endophilin A recruitment to sites of clathrin-mediated SV recycling, thereby facilitating vesicle uncoating. PMID:25520322