WorldWideScience

Sample records for binding pocket similarity

  1. PoSSuM: a database of similar protein–ligand binding and putative pockets

    OpenAIRE

    Ito, Jun-ichi; Tabei, Yasuo; Shimizu, Kana; Tsuda, Koji; Tomii, Kentaro

    2011-01-01

    Numerous potential ligand-binding sites are available today, along with hundreds of thousands of known binding sites observed in the PDB. Exhaustive similarity search for such vastly numerous binding site pairs is useful to predict protein functions and to enable rapid screening of target proteins for drug design. Existing databases of ligand-binding sites offer databases of limited scale. For example, SitesBase covers only ∼33 000 known binding sites. Inferring protein function and drug disc...

  2. A new protein binding pocket similarity measure based on comparison of 3D atom clouds: application to ligand prediction

    OpenAIRE

    Hoffmann, Brice; Zaslavskiy, Mikhail; Vert, Jean-Philippe; Stoven, Véronique

    2009-01-01

    Motivation: Prediction of ligands for proteins of known 3D structure is important to understand structure-function relationship, predict molecular function, or design new drugs.\\\\ Results: We explore a new approach for ligand prediction in which binding pockets are represented by atom clouds. Each target pocket is compared to an ensemble of pockets of known ligands. Pockets are aligned in 3D space with further use of convolution kernels between clouds of points. Performance of the new method ...

  3. Definition of the G protein-coupled receptor transmembrane bundle binding pocket and calculation of receptor similarities for drug design

    DEFF Research Database (Denmark)

    Gloriam, David Erik Immanuel; Foord, Steven M; Blaney, Frank E;

    2009-01-01

    currently available crystal structures. This was used to characterize pharmacological relationships of Family A/Rhodopsin family GPCRs, minimizing evolutionary influence from parts of the receptor that do not generally affect ligand binding. The resultant dendogram tended to group receptors according to...

  4. POVME: An Algorithm for Measuring Binding-Pocket Volumes

    OpenAIRE

    Durrant, Jacob D; de Oliveira, César Augusto F; McCammon, J. Andrew

    2010-01-01

    Researchers engaged in computer-aided drug design often wish to measure the volume of a ligand-binding pocket in order to predict pharmacology. We have recently developed a simple algorithm, called POVME (POcket Volume MEasurer), for this purpose. POVME is Python implemented, fast, and freely available. To demonstrate its utility, we use the new algorithm to study three members of the matrix-metalloproteinase family of proteins. Despite the structural similarity of these proteins, differences...

  5. Computational analysis of HIV-1 protease protein binding pockets.

    Science.gov (United States)

    Ko, Gene M; Reddy, A Srinivas; Kumar, Sunil; Bailey, Barbara A; Garg, Rajni

    2010-10-25

    Mutations that arise in HIV-1 protease after exposure to various HIV-1 protease inhibitors have proved to be a difficult aspect in the treatment of HIV. Mutations in the binding pocket of the protease can prevent the protease inhibitor from binding to the protein effectively. In the present study, the crystal structures of 68 HIV-1 proteases complexed with one of the nine FDA approved protease inhibitors from the Protein Data Bank (PDB) were analyzed by (a) identifying the mutational changes with the aid of a developed mutation map and (b) correlating the structure of the binding pockets with the complexed inhibitors. The mutations of each crystal structure were identified by comparing the amino acid sequence of each structure against the HIV-1 wild-type strain HXB2. These mutations were visually presented in the form of a mutation map to analyze mutation patterns corresponding to each protease inhibitor. The crystal structure mutation patterns of each inhibitor (in vitro) were compared against the mutation patterns observed in in vivo data. The in vitro mutation patterns were found to be representative of most of the major in vivo mutations. We then performed a data mining analysis of the binding pockets from each crystal structure in terms of their chemical descriptors to identify important structural features of the HIV-1 protease protein with respect to the binding conformation of the HIV-1 protease inhibitors. Data mining analysis is performed using several classification techniques: Random Forest (RF), linear discriminant analysis (LDA), and logistic regression (LR). We developed two hybrid models, RF-LDA and RF-LR. Random Forest is used as a feature selection proxy, reducing the descriptor space to a few of the most relevant descriptors determined by the classifier. These descriptors are then used to develop the subsequent LDA, LR, and hierarchical classification models. Clustering analysis of the binding pockets using the selected descriptors used to

  6. Free enthalpies of replacing water molecules in protein binding pockets.

    Science.gov (United States)

    Riniker, Sereina; Barandun, Luzi J; Diederich, François; Krämer, Oliver; Steffen, Andreas; van Gunsteren, Wilfred F

    2012-12-01

    Water molecules in the binding pocket of a protein and their role in ligand binding have increasingly raised interest in recent years. Displacement of such water molecules by ligand atoms can be either favourable or unfavourable for ligand binding depending on the change in free enthalpy. In this study, we investigate the displacement of water molecules by an apolar probe in the binding pocket of two proteins, cyclin-dependent kinase 2 and tRNA-guanine transglycosylase, using the method of enveloping distribution sampling (EDS) to obtain free enthalpy differences. In both cases, a ligand core is placed inside the respective pocket and the remaining water molecules are converted to apolar probes, both individually and in pairs. The free enthalpy difference between a water molecule and a CH(3) group at the same location in the pocket in comparison to their presence in bulk solution calculated from EDS molecular dynamics simulations corresponds to the binding free enthalpy of CH(3) at this location. From the free enthalpy difference and the enthalpy difference, the entropic contribution of the displacement can be obtained too. The overlay of the resulting occupancy volumes of the water molecules with crystal structures of analogous ligands shows qualitative correlation between experimentally measured inhibition constants and the calculated free enthalpy differences. Thus, such an EDS analysis of the water molecules in the binding pocket may give valuable insight for potency optimization in drug design. PMID:23247390

  7. The distribution of ligand-binding pockets around protein-protein interfaces suggests a general mechanism for pocket formation

    OpenAIRE

    Gao, Mu; Skolnick, Jeffrey

    2012-01-01

    Protein-protein and protein-ligand interactions are ubiquitous in a biological cell. Here, we report a comprehensive study of the distribution of protein-ligand interaction sites, namely ligand-binding pockets, around protein-protein interfaces where protein-protein interactions occur. We inspected a representative set of 1,611 representative protein-protein complexes and identified pockets with a potential for binding small molecule ligands. The majority of these pockets are within a 6 Å dis...

  8. Importance of a Hydrophobic Pocket for Peptide Binding in Lactococcal OppA▿

    OpenAIRE

    Berntsson, Ronnie P-A; Thunnissen, Andy-Mark W H; Poolman, Bert; Slotboom, Dirk-Jan

    2011-01-01

    Lactococcal oligopeptide-binding protein A (OppA) binds peptides with widely varied lengths and sequences. We previously hypothesized that a hydrophobic pocket in OppA preferentially binds a hydrophobic peptide side chain and thus determines its binding register. Two crystal structures of OppA with different nonapeptides now indeed show binding in different registers.

  9. Do drugs have access to the P-glycoprotein drug-binding pocket through gates?

    Science.gov (United States)

    Ferreira, Ricardo J; Ferreira, Maria-José U; Dos Santos, Daniel J V A

    2015-10-13

    The P-glycoprotein efflux mechanism is being studied since its identification as a leading protagonist in multidrug resistance. Recently, it was suggested that drugs enter the drug-binding pocket (DBP) through gates located between the transmembrane domains. For both a substrate and a modulator, the potential of mean force curves along the reaction coordinate obtained with the WHAM approach were similar, with no activation energy required for crossing the gate. Moreover, drug transit from bulk water into the DBP was characterized as an overall free-energy downhill process. PMID:26574244

  10. The minor binding pocket: a major player in 7TM receptor activation

    DEFF Research Database (Denmark)

    Rosenkilde, Mette Marie; Benned-Jensen, Tau; Frimurer, Thomas M.;

    2010-01-01

    interface between TM-II and TM-VII being of particular significance. Importantly, the minor binding pocket, especially the proline-kink in TM-II, is involved in G protein versus arrestin pathway-biased signaling, for example in the angiotensin AT1 system. Consequently, this pocket could be specifically...

  11. Divergence of Pumilio/fem-3 mRNA Binding Factor (PUF) Protein Specificity through Variations in an RNA-binding Pocket*

    Science.gov (United States)

    Qiu, Chen; Kershner, Aaron; Wang, Yeming; Holley, Cynthia P.; Wilinski, Daniel; Keles, Sunduz; Kimble, Judith; Wickens, Marvin; Hall, Traci M. Tanaka

    2012-01-01

    mRNA control networks depend on recognition of specific RNA sequences. Pumilio-fem-3 mRNA binding factor (PUF) RNA-binding proteins achieve that specificity through variations on a conserved scaffold. Saccharomyces cerevisiae Puf3p achieves specificity through an additional binding pocket for a cytosine base upstream of the core RNA recognition site. Here we demonstrate that this chemically simple adaptation is prevalent and contributes to the diversity of RNA specificities among PUF proteins. Bioinformatics analysis shows that mRNAs associated with Caenorhabditis elegans fem-3 mRNA binding factor (FBF)-2 in vivo contain an upstream cytosine required for biological regulation. Crystal structures of FBF-2 and C. elegans PUF-6 reveal binding pockets structurally similar to that of Puf3p, whereas sequence alignments predict a pocket in PUF-11. For Puf3p, FBF-2, PUF-6, and PUF-11, the upstream pockets and a cytosine are required for maximal binding to RNA, but the quantitative impact on binding affinity varies. Furthermore, the position of the upstream cytosine relative to the core PUF recognition site can differ, which in the case of FBF-2 originally masked the identification of this consensus sequence feature. Importantly, other PUF proteins lack the pocket and so do not discriminate upstream bases. A structure-based alignment reveals that these proteins lack key residues that would contact the cytosine, and in some instances, they also present amino acid side chains that interfere with binding. Loss of the pocket requires only substitution of one serine, as appears to have occurred during the evolution of certain fungal species. PMID:22205700

  12. Divergence of Pumilio/fem-3 mRNA binding factor (PUF) protein specificity through variations in an RNA-binding pocket.

    Science.gov (United States)

    Qiu, Chen; Kershner, Aaron; Wang, Yeming; Holley, Cynthia P; Wilinski, Daniel; Keles, Sunduz; Kimble, Judith; Wickens, Marvin; Hall, Traci M Tanaka

    2012-02-24

    mRNA control networks depend on recognition of specific RNA sequences. Pumilio-fem-3 mRNA binding factor (PUF) RNA-binding proteins achieve that specificity through variations on a conserved scaffold. Saccharomyces cerevisiae Puf3p achieves specificity through an additional binding pocket for a cytosine base upstream of the core RNA recognition site. Here we demonstrate that this chemically simple adaptation is prevalent and contributes to the diversity of RNA specificities among PUF proteins. Bioinformatics analysis shows that mRNAs associated with Caenorhabditis elegans fem-3 mRNA binding factor (FBF)-2 in vivo contain an upstream cytosine required for biological regulation. Crystal structures of FBF-2 and C. elegans PUF-6 reveal binding pockets structurally similar to that of Puf3p, whereas sequence alignments predict a pocket in PUF-11. For Puf3p, FBF-2, PUF-6, and PUF-11, the upstream pockets and a cytosine are required for maximal binding to RNA, but the quantitative impact on binding affinity varies. Furthermore, the position of the upstream cytosine relative to the core PUF recognition site can differ, which in the case of FBF-2 originally masked the identification of this consensus sequence feature. Importantly, other PUF proteins lack the pocket and so do not discriminate upstream bases. A structure-based alignment reveals that these proteins lack key residues that would contact the cytosine, and in some instances, they also present amino acid side chains that interfere with binding. Loss of the pocket requires only substitution of one serine, as appears to have occurred during the evolution of certain fungal species. PMID:22205700

  13. Visualisation of variable binding pockets on protein surfaces by probabilistic analysis of related structure sets

    Directory of Open Access Journals (Sweden)

    Ashford Paul

    2012-03-01

    Full Text Available Abstract Background Protein structures provide a valuable resource for rational drug design. For a protein with no known ligand, computational tools can predict surface pockets that are of suitable size and shape to accommodate a complementary small-molecule drug. However, pocket prediction against single static structures may miss features of pockets that arise from proteins' dynamic behaviour. In particular, ligand-binding conformations can be observed as transiently populated states of the apo protein, so it is possible to gain insight into ligand-bound forms by considering conformational variation in apo proteins. This variation can be explored by considering sets of related structures: computationally generated conformers, solution NMR ensembles, multiple crystal structures, homologues or homology models. It is non-trivial to compare pockets, either from different programs or across sets of structures. For a single structure, difficulties arise in defining particular pocket's boundaries. For a set of conformationally distinct structures the challenge is how to make reasonable comparisons between them given that a perfect structural alignment is not possible. Results We have developed a computational method, Provar, that provides a consistent representation of predicted binding pockets across sets of related protein structures. The outputs are probabilities that each atom or residue of the protein borders a predicted pocket. These probabilities can be readily visualised on a protein using existing molecular graphics software. We show how Provar simplifies comparison of the outputs of different pocket prediction algorithms, of pockets across multiple simulated conformations and between homologous structures. We demonstrate the benefits of use of multiple structures for protein-ligand and protein-protein interface analysis on a set of complexes and consider three case studies in detail: i analysis of a kinase superfamily highlights the

  14. Doubling the Size of the Glucocorticoid Receptor Ligand Binding Pocket by Deacylcortivazol

    Energy Technology Data Exchange (ETDEWEB)

    Suino-Powell, Kelly; Xu, Yong; Zhang, Chenghai; Tao, Yong-guang; Tolbert, W. David; Simons, Jr., S. Stoney; Xu, H. Eric (NIH)

    2010-03-08

    A common feature of nuclear receptor ligand binding domains (LBD) is a helical sandwich fold that nests a ligand binding pocket within the bottom half of the domain. Here we report that the ligand pocket of glucocorticoid receptor (GR) can be continuously extended into the top half of the LBD by binding to deacylcortivazol (DAC), an extremely potent glucocorticoid. It has been puzzling for decades why DAC, which contains a phenylpyrazole replacement at the conserved 3-ketone of steroid hormones that are normally required for activation of their cognate receptors, is a potent GR activator. The crystal structure of the GR LBD bound to DAC and the fourth LXXLL motif of steroid receptor coactivator 1 reveals that the GR ligand binding pocket is expanded to a size of 1,070 {angstrom}{sup 3}, effectively doubling the size of the GR dexamethasone-binding pocket of 540 {angstrom}{sup 3} and yet leaving the structure of the coactivator binding site intact. DAC occupies only {approx}50% of the space of the pocket but makes intricate interactions with the receptor around the phenylpyrazole group that accounts for the high-affinity binding of DAC. The dramatic expansion of the DAC-binding pocket thus highlights the conformational adaptability of GR to ligand binding. The new structure also allows docking of various nonsteroidal ligands that cannot be fitted into the previous structures, thus providing a new rational template for drug discovery of steroidal and nonsteroidal glucocorticoids that can be specifically designed to reach the unoccupied space of the expanded pocket.

  15. Solvent fluctuations induce non-Markovian kinetics in hydrophobic pocket-ligand binding

    CERN Document Server

    Weiß, R Gregor; Dzubiella, Joachim

    2016-01-01

    We investigate the impact of water fluctuations on the key-lock association kinetics of a hydrophobic ligand (key) binding to a hydrophobic pocket (lock) by means of a minimalistic stochastic model system. It describes the collective hydration behavior of the pocket by bimodal fluctuations of a water-pocket interface that dynamically couples to the diffusive motion of the approaching ligand via the hydrophobic interaction. This leads to a set of overdamped Langevin equations in 2D-coordinate-space, that is Markovian in each dimension. Numerical simulations demonstrate locally increased friction of the ligand, decelerated binding kinetics, and local non-Markovian (memory) effects in the ligand's reaction coordinate as found previously in explicit-water molecular dynamics studies of model hydrophobic pocket-ligand binding [1,2]. Our minimalistic model elucidates the origin of effectively enhanced friction in the process that can be traced back to long-time decays in the force-autocorrelation function induced by...

  16. Specificity of anion-binding in the substrate-pocket ofbacteriorhodopsin

    Energy Technology Data Exchange (ETDEWEB)

    Facciotti, Marc T.; Cheung, Vincent S.; Lunde, Christopher S.; Rouhani, Shahab; Baliga, Nitin S.; Glaeser, Robert M.

    2003-08-30

    The structure of the D85S mutant of bacteriorhodopsin with a nitrate anion bound in the Schiff-base binding site, and the structure of the anion-free protein have been obtained in the same crystal form. Together with the previously solved structures of this anion pump, in both the anion-free state and bromide-bound state, these new structures provide insight into how this mutant of bacteriorhodopsin is able to bind a variety of different anions in the same binding pocket. The structural analysis reveals that the main structural change that accommodates different anions is the repositioning of the polar side-chain of S85. On the basis of these x-ray crystal structures, the prediction is then made that the D85S/D212N double mutant might bind similar anions and do so over a broader pH range than does the single mutant. Experimental comparison of the dissociation constants, K{sub d}, for a variety of anions confirms this prediction and demonstrates, in addition, that the binding affinity is dramatically improved by the D212N substitution.

  17. Conformational Plasticity of the NNRTI-Binding Pocket in HIV-1 Reverse Transcriptase: A Fluorine Nuclear Magnetic Resonance Study.

    Science.gov (United States)

    Sharaf, Naima G; Ishima, Rieko; Gronenborn, Angela M

    2016-07-19

    HIV-1 reverse transcriptase (RT) is a major drug target in the treatment of HIV-1 infection. RT inhibitors currently in use include non-nucleoside, allosteric RT inhibitors (NNRTIs), which bind to a hydrophobic pocket, distinct from the enzyme's active site. We investigated RT-NNRTI interactions by solution (19)F nuclear magnetic resonance (NMR), using singly (19)F-labeled RT proteins. Comparison of (19)F chemical shifts of fluorinated RT and drug-resistant variants revealed that the fluorine resonance is a sensitive probe for identifying mutation-induced changes in the enzyme. Our data show that in the unliganded enzyme, the NNRTI-binding pocket is highly plastic and not locked into a single conformation. Upon inhibitor binding, the binding pocket becomes rigidified. In the inhibitor-bound state, the (19)F signal of RT is similar to that of drug-resistant mutant enzymes, distinct from what is observed for the free state. Our results demonstrate the power of (19)F NMR spectroscopy to characterize conformational properties using selectively (19)F-labeled protein. PMID:27163463

  18. Computational fragment-based drug design to explore the hydrophobic sub-pocket of the mitotic kinesin Eg5 allosteric binding site.

    Science.gov (United States)

    Oguievetskaia, Ksenia; Martin-Chanas, Laetitia; Vorotyntsev, Artem; Doppelt-Azeroual, Olivia; Brotel, Xavier; Adcock, Stewart A; de Brevern, Alexandre G; Delfaud, Francois; Moriaud, Fabrice

    2009-08-01

    Eg5, a mitotic kinesin exclusively involved in the formation and function of the mitotic spindle has attracted interest as an anticancer drug target. Eg5 is co-crystallized with several inhibitors bound to its allosteric binding pocket. Each of these occupies a pocket formed by loop 5/helix alpha2 (L5/alpha2). Recently designed inhibitors additionally occupy a hydrophobic pocket of this site. The goal of the present study was to explore this hydrophobic pocket with our MED-SuMo fragment-based protocol, and thus discover novel chemical structures that might bind as inhibitors. The MED-SuMo software is able to compare and superimpose similar interaction surfaces upon the whole protein data bank (PDB). In a fragment-based protocol, MED-SuMo retrieves MED-Portions that encode protein-fragment binding sites and are derived from cross-mining protein-ligand structures with libraries of small molecules. Furthermore we have excluded intra-family MED-Portions derived from Eg5 ligands that occupy the hydrophobic pocket and predicted new potential ligands by hybridization that would fill simultaneously both pockets. Some of the latter having original scaffolds and substituents in the hydrophobic pocket are identified in libraries of synthetically accessible molecules by the MED-Search software. PMID:19533373

  19. Microbial diversity similarities in periodontal pockets and atheromatous plaques of cardiovascular disease patients.

    Directory of Open Access Journals (Sweden)

    Wagner Serra e Silva Filho

    Full Text Available BACKGROUND AND OBJECTIVE: The immune and infectious alterations occurring in periodontitis have been shown to alter the development and severity of cardiovascular disease. One of these relationships is the translocation of oral bacteria to atheroma plaques, thereby promoting plaque development. Thus, the aim of this study was to assess, by 16s cloning and sequencing, the microbial diversity of the subgingival environment and atheroma plaques of patients concomitantly suffering from periodontitis and obstructive coronary artery atherosclerosis (OCAA. METHODS: Subgingival biofilm and coronary balloons used in percutaneous transluminal coronary angioplasty were collected from 18 subjects presenting with generalized moderate to severe periodontitis and OCAA. DNA was extracted and the gene 16S was amplified, cloned and sequenced. RESULTS: Significant differences in microbial diversity were observed between both environments. While subgingival samples mostly contained the phylum Firmicutes, in coronary balloons, Proteobacteria (p<0.05 was predominant. In addition, the most commonly detected genera in coronary balloons were Acinetobacter, Alloprevotella, Pseudomonas, Enterobacter, Sphingomonas and Moraxella, while in subgingival samples Porphyromonas, Filifactor, Veillonella, Aggregatibacter and Treponema (p<0.05 were found. Interestingly, 17 identical phylotypes were found in atheroma and subgingival samples, indicating possible bacterial translocation between periodontal pockets and coronary arteries. CONCLUSION: Periodontal pockets and atheromatous plaques of cardiovascular disease patients can present similarities in the microbial diversity.

  20. The XRCC1 phosphate-binding pocket binds poly (ADP-ribose) and is required for XRCC1 function.

    Science.gov (United States)

    Breslin, Claire; Hornyak, Peter; Ridley, Andrew; Rulten, Stuart L; Hanzlikova, Hana; Oliver, Antony W; Caldecott, Keith W

    2015-08-18

    Poly (ADP-ribose) is synthesized at DNA single-strand breaks and can promote the recruitment of the scaffold protein, XRCC1. However, the mechanism and importance of this process has been challenged. To address this issue, we have characterized the mechanism of poly (ADP-ribose) binding by XRCC1 and examined its importance for XRCC1 function. We show that the phosphate-binding pocket in the central BRCT1 domain of XRCC1 is required for selective binding to poly (ADP-ribose) at low levels of ADP-ribosylation, and promotes interaction with cellular PARP1. We also show that the phosphate-binding pocket is required for EGFP-XRCC1 accumulation at DNA damage induced by UVA laser, H2O2, and at sites of sub-nuclear PCNA foci, suggesting that poly (ADP-ribose) promotes XRCC1 recruitment both at single-strand breaks globally across the genome and at sites of DNA replication stress. Finally, we show that the phosphate-binding pocket is required following DNA damage for XRCC1-dependent acceleration of DNA single-strand break repair, DNA base excision repair, and cell survival. These data support the hypothesis that poly (ADP-ribose) synthesis promotes XRCC1 recruitment at DNA damage sites and is important for XRCC1 function. PMID:26130715

  1. The XRCC1 phosphate-binding pocket binds poly (ADP-ribose) and is required for XRCC1 function

    Science.gov (United States)

    Breslin, Claire; Hornyak, Peter; Ridley, Andrew; Rulten, Stuart L.; Hanzlikova, Hana; Oliver, Antony W.; Caldecott, Keith W.

    2015-01-01

    Poly (ADP-ribose) is synthesized at DNA single-strand breaks and can promote the recruitment of the scaffold protein, XRCC1. However, the mechanism and importance of this process has been challenged. To address this issue, we have characterized the mechanism of poly (ADP-ribose) binding by XRCC1 and examined its importance for XRCC1 function. We show that the phosphate-binding pocket in the central BRCT1 domain of XRCC1 is required for selective binding to poly (ADP-ribose) at low levels of ADP-ribosylation, and promotes interaction with cellular PARP1. We also show that the phosphate-binding pocket is required for EGFP-XRCC1 accumulation at DNA damage induced by UVA laser, H2O2, and at sites of sub-nuclear PCNA foci, suggesting that poly (ADP-ribose) promotes XRCC1 recruitment both at single-strand breaks globally across the genome and at sites of DNA replication stress. Finally, we show that the phosphate-binding pocket is required following DNA damage for XRCC1-dependent acceleration of DNA single-strand break repair, DNA base excision repair, and cell survival. These data support the hypothesis that poly (ADP-ribose) synthesis promotes XRCC1 recruitment at DNA damage sites and is important for XRCC1 function. PMID:26130715

  2. Re-designing the substrate binding pocket of laccase for enhanced oxidation of sinapic acid

    OpenAIRE

    Pardo, Isabel; Santiago, Gerard; Gentili, Patrizia; Lucas, Fátima; Monza, Emanuele; Medrano, Francisco Javier; Galli, Carlo; Martínez, Angel T.; Guallar, Víctor; Camarero, Susana

    2015-01-01

    Iterative saturation mutagenesis was performed over six residues delimiting the substrate binding pocket of a high redox potential chimeric laccase with the aim of enhancing its activity over sinapic acid, a ligninrelated phenol of industrial interest. In total, more than 15000 clones were screened and two selected variants, together with the parent-type laccase, were purified and characterized. The new variants presented shifted pH activity profiles and enhanced turnover rates on sinapic aci...

  3. The structure of the SBP-Tag–streptavidin complex reveals a novel helical scaffold bridging binding pockets on separate subunits

    Energy Technology Data Exchange (ETDEWEB)

    Barrette-Ng, Isabelle H.; Wu, Sau-Ching; Tjia, Wai-Mui; Wong, Sui-Lam; Ng, Kenneth K. S., E-mail: ngk@ucalgary.ca [University of Calgary, 2500 University Drive NW, Calgary, Alberta T2N 1N4 (Canada)

    2013-05-01

    The structure of the SBP-Tag–streptavidin complex reveals a novel mode of peptide recognition in which a single peptide binds simultaneously to biotin-binding pockets from adjacent subunits of streptavidin. The molecular details of peptide recognition suggest how the SBP-Tag can be further modified to become an even more useful tag for a wider range of biotechnological applications. The 38-residue SBP-Tag binds to streptavidin more tightly (K{sub d} ≃ 2.5–4.9 nM) than most if not all other known peptide sequences. Crystallographic analysis at 1.75 Å resolution shows that the SBP-Tag binds to streptavidin in an unprecedented manner by simultaneously interacting with biotin-binding pockets from two separate subunits. An N-terminal HVV peptide sequence (residues 12–14) and a C-terminal HPQ sequence (residues 31–33) form the bulk of the direct interactions between the SBP-Tag and the two biotin-binding pockets. Surprisingly, most of the peptide spanning these two sites (residues 17–28) adopts a regular α-helical structure that projects three leucine side chains into a groove formed at the interface between two streptavidin protomers. The crystal structure shows that residues 1–10 and 35–38 of the original SBP-Tag identified through in vitro selection and deletion analysis do not appear to contact streptavidin and thus may not be important for binding. A 25-residue peptide comprising residues 11–34 (SBP-Tag2) was synthesized and shown using surface plasmon resonance to bind streptavidin with very similar affinity and kinetics when compared with the SBP-Tag. The SBP-Tag2 was also added to the C-terminus of β-lactamase and was shown to be just as effective as the full-length SBP-Tag in affinity purification. These results validate the molecular structure of the SBP-Tag–streptavidin complex and establish a minimal bivalent streptavidin-binding tag from which further rational design and optimization can proceed.

  4. Retinoid-binding proteins: similar protein architectures bind similar ligands via completely different ways.

    Directory of Open Access Journals (Sweden)

    Yu-Ru Zhang

    Full Text Available BACKGROUND: Retinoids are a class of compounds that are chemically related to vitamin A, which is an essential nutrient that plays a key role in vision, cell growth and differentiation. In vivo, retinoids must bind with specific proteins to perform their necessary functions. Plasma retinol-binding protein (RBP and epididymal retinoic acid binding protein (ERABP carry retinoids in bodily fluids, while cellular retinol-binding proteins (CRBPs and cellular retinoic acid-binding proteins (CRABPs carry retinoids within cells. Interestingly, although all of these transport proteins possess similar structures, the modes of binding for the different retinoid ligands with their carrier proteins are different. METHODOLOGY/PRINCIPAL FINDINGS: In this work, we analyzed the various retinoid transport mechanisms using structure and sequence comparisons, binding site analyses and molecular dynamics simulations. Our results show that in the same family of proteins and subcellular location, the orientation of a retinoid molecule within a binding protein is same, whereas when different families of proteins are considered, the orientation of the bound retinoid is completely different. In addition, none of the amino acid residues involved in ligand binding is conserved between the transport proteins. However, for each specific binding protein, the amino acids involved in the ligand binding are conserved. The results of this study allow us to propose a possible transport model for retinoids. CONCLUSIONS/SIGNIFICANCE: Our results reveal the differences in the binding modes between the different retinoid-binding proteins.

  5. Computational approaches for identification of conserved/unique binding pockets in the A chain of ricin

    Energy Technology Data Exchange (ETDEWEB)

    Ecale Zhou, C L; Zemla, A T; Roe, D; Young, M; Lam, M; Schoeniger, J; Balhorn, R

    2005-01-29

    Specific and sensitive ligand-based protein detection assays that employ antibodies or small molecules such as peptides, aptamers, or other small molecules require that the corresponding surface region of the protein be accessible and that there be minimal cross-reactivity with non-target proteins. To reduce the time and cost of laboratory screening efforts for diagnostic reagents, we developed new methods for evaluating and selecting protein surface regions for ligand targeting. We devised combined structure- and sequence-based methods for identifying 3D epitopes and binding pockets on the surface of the A chain of ricin that are conserved with respect to a set of ricin A chains and unique with respect to other proteins. We (1) used structure alignment software to detect structural deviations and extracted from this analysis the residue-residue correspondence, (2) devised a method to compare corresponding residues across sets of ricin structures and structures of closely related proteins, (3) devised a sequence-based approach to determine residue infrequency in local sequence context, and (4) modified a pocket-finding algorithm to identify surface crevices in close proximity to residues determined to be conserved/unique based on our structure- and sequence-based methods. In applying this combined informatics approach to ricin A we identified a conserved/unique pocket in close proximity (but not overlapping) the active site that is suitable for bi-dentate ligand development. These methods are generally applicable to identification of surface epitopes and binding pockets for development of diagnostic reagents, therapeutics, and vaccines.

  6. eMatchSite: sequence order-independent structure alignments of ligand binding pockets in protein models.

    Directory of Open Access Journals (Sweden)

    Michal Brylinski

    2014-09-01

    Full Text Available Detecting similarities between ligand binding sites in the absence of global homology between target proteins has been recognized as one of the critical components of modern drug discovery. Local binding site alignments can be constructed using sequence order-independent techniques, however, to achieve a high accuracy, many current algorithms for binding site comparison require high-quality experimental protein structures, preferably in the bound conformational state. This, in turn, complicates proteome scale applications, where only various quality structure models are available for the majority of gene products. To improve the state-of-the-art, we developed eMatchSite, a new method for constructing sequence order-independent alignments of ligand binding sites in protein models. Large-scale benchmarking calculations using adenine-binding pockets in crystal structures demonstrate that eMatchSite generates accurate alignments for almost three times more protein pairs than SOIPPA. More importantly, eMatchSite offers a high tolerance to structural distortions in ligand binding regions in protein models. For example, the percentage of correctly aligned pairs of adenine-binding sites in weakly homologous protein models is only 4-9% lower than those aligned using crystal structures. This represents a significant improvement over other algorithms, e.g. the performance of eMatchSite in recognizing similar binding sites is 6% and 13% higher than that of SiteEngine using high- and moderate-quality protein models, respectively. Constructing biologically correct alignments using predicted ligand binding sites in protein models opens up the possibility to investigate drug-protein interaction networks for complete proteomes with prospective systems-level applications in polypharmacology and rational drug repositioning. eMatchSite is freely available to the academic community as a web-server and a stand-alone software distribution at http://www.brylinski.org/ematchsite.

  7. Identification of a Ligand Binding Pocket in LdtR from Liberibacter asiaticus.

    Science.gov (United States)

    Pagliai, Fernando A; Gonzalez, Claudio F; Lorca, Graciela L

    2015-01-01

    LdtR is a transcriptional activator involved in the regulation of a putative L,D transpeptidase in Liberibacter asiaticus, an unculturable pathogen and one of the causative agents of Huanglongbing disease. Using small molecule screens we identified benzbromarone as an inhibitor of LdtR activity, which was confirmed using in vivo and in vitro assays. Based on these previous results, the objective of this work was to identify the LdtR ligand binding pocket and characterize its interactions with benzbromarone. A structural model of LdtR was constructed and the molecular interactions with the ligand were predicted using the SwissDock interface. Using site-directed mutagenesis, these residues were changed to alanine. Electrophoretic mobility shift assays, thermal denaturation, isothermal titration calorimetry experiments, and in vivo assays were used to identify residues T43, L61, and F64 in the Benz1 pocket of LdtR as the amino acids most likely involved in the binding to benzbromarone. These results provide new information on the binding mechanism of LdtR to a modulatory molecule and provide a blue print for the design of therapeutics for other members of the MarR family of transcriptional regulators involved in pathogenicity. PMID:26635775

  8. Influences of the Hydrophobicity of the Heme-binding Pocket on the Propreties and Functions of Cytochrome b5 Mutants

    Institute of Scientific and Technical Information of China (English)

    GAN, Jian-Hua; WANG, Yun-Hua; WU, Jian; HUANG, Zhong-Xian; XIA, Zong-Xiang

    2003-01-01

    The mutation sites of the four mutants F35Y, P40V, V45E and V45Y of cytochrome b5 are located at the edge of the hemebinding pocket. The solvent accessible areas of the "pocket interior" of the four mutants and the wild-type cytochrome b5 have been calculated based on their crystal structures at high resolution. The change in the hydrophobicity of the heme-binding pocket resulting from the mutation can be quantitatively described using the difference of the solvent accessible area of the "pocket interior" of each mutant from that of the wild-type cytochrome b5. The influences of the hydrophobicity of the hemebinding pocket on the protein stability and redox potential are discussed.

  9. Allosteric coupling from G protein to the agonist-binding pocket in GPCRs.

    Science.gov (United States)

    DeVree, Brian T; Mahoney, Jacob P; Vélez-Ruiz, Gisselle A; Rasmussen, Soren G F; Kuszak, Adam J; Edwald, Elin; Fung, Juan-Jose; Manglik, Aashish; Masureel, Matthieu; Du, Yang; Matt, Rachel A; Pardon, Els; Steyaert, Jan; Kobilka, Brian K; Sunahara, Roger K

    2016-07-01

    G-protein-coupled receptors (GPCRs) remain the primary conduit by which cells detect environmental stimuli and communicate with each other. Upon activation by extracellular agonists, these seven-transmembrane-domain-containing receptors interact with heterotrimeric G proteins to regulate downstream second messenger and/or protein kinase cascades. Crystallographic evidence from a prototypic GPCR, the β2-adrenergic receptor (β2AR), in complex with its cognate G protein, Gs, has provided a model for how agonist binding promotes conformational changes that propagate through the GPCR and into the nucleotide-binding pocket of the G protein α-subunit to catalyse GDP release, the key step required for GTP binding and activation of G proteins. The structure also offers hints about how G-protein binding may, in turn, allosterically influence ligand binding. Here we provide functional evidence that G-protein coupling to the β2AR stabilizes a ‘closed’ receptor conformation characterized by restricted access to and egress from the hormone-binding site. Surprisingly, the effects of G protein on the hormone-binding site can be observed in the absence of a bound agonist, where G-protein coupling driven by basal receptor activity impedes the association of agonists, partial agonists, antagonists and inverse agonists. The ability of bound ligands to dissociate from the receptor is also hindered, providing a structural explanation for the G-protein-mediated enhancement of agonist affinity, which has been observed for many GPCR–G-protein pairs. Our data also indicate that, in contrast to agonist binding alone, coupling of a G protein in the absence of an agonist stabilizes large structural changes in a GPCR. The effects of nucleotide-free G protein on ligand-binding kinetics are shared by other members of the superfamily of GPCRs, suggesting that a common mechanism may underlie G-protein-mediated enhancement of agonist affinity. PMID:27362234

  10. The same pocket in menin binds both MLL and JUND but has opposite effects on transcription

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Jing; Gurung, Buddha; Wan, Bingbing; Matkar, Smita; Veniaminova, Natalia A.; Wan, Ke; Merchant, Juanita L.; Hua, Xianxin; Lei, Ming (Michigan); (Michigan-Med); (UPENN-MED)

    2013-04-08

    Menin is a tumour suppressor protein whose loss or inactivation causes multiple endocrine neoplasia 1 (MEN1), a hereditary autosomal dominant tumour syndrome that is characterized by tumorigenesis in multiple endocrine organs. Menin interacts with many proteins and is involved in a variety of cellular processes. Menin binds the JUN family transcription factor JUND and inhibits its transcriptional activity. Several MEN1 missense mutations disrupt the menin-JUND interaction, suggesting a correlation between the tumour-suppressor function of menin and its suppression of JUND-activated transcription. Menin also interacts with mixed lineage leukaemia protein 1 (MLL1), a histone H3 lysine 4 methyltransferase, and functions as an oncogenic cofactor to upregulate gene transcription and promote MLL1-fusion-protein-induced leukaemogenesis. A recent report on the tethering of MLL1 to chromatin binding factor lens epithelium-derived growth factor (LEDGF) by menin indicates that menin is a molecular adaptor coordinating the functions of multiple proteins. Despite its importance, how menin interacts with many distinct partners and regulates their functions remains poorly understood. Here we present the crystal structures of human menin in its free form and in complexes with MLL1 or with JUND, or with an MLL1-LEDGF heterodimer. These structures show that menin contains a deep pocket that binds short peptides of MLL1 or JUND in the same manner, but that it can have opposite effects on transcription. The menin-JUND interaction blocks JUN N-terminal kinase (JNK)-mediated JUND phosphorylation and suppresses JUND-induced transcription. In contrast, menin promotes gene transcription by binding the transcription activator MLL1 through the peptide pocket while still interacting with the chromatin-anchoring protein LEDGF at a distinct surface formed by both menin and MLL1.

  11. Selective membrane disruption by the cyclotide kalata B7: complex ions and essential functional groups in the phosphatidylethanolamine binding pocket.

    Science.gov (United States)

    Strömstedt, Adam A; Kristiansen, Per Eugen; Gunasekera, Sunithi; Grob, Nathalie; Skjeldal, Lars; Göransson, Ulf

    2016-06-01

    The cyclic cystine knot plant peptides called cyclotides are active against a wide variety of organisms. This is primarily achieved through membrane binding and disruption, in part deriving from a high affinity for phosphatidylethanolamine (PE) lipids. Some cyclotides, such as kalata B7 (kB7), form complexes with divalent cations in a pocket associated with the tyrosine residue at position 15 (Tyr15). In the current work we explore the effect of cations on membrane leakage caused by cyclotides kB1, kB2 and kB7, and we identify a functional group that is essential for PE selectivity. The presence of PE-lipids in liposomes increased the membrane permeabilizing potency of the cyclotides, with the potency of kB7 increasing by as much as 740-fold. The divalent cations Mn(2+), Mg(2+) and Ca(2+) had no apparent effect on PE selectivity. However, amino acid substitutions in kB7 proved that Tyr15 is crucial for PE-selective membrane permeabilization on various liposome systems. Although the tertiary structure of kB7 was maintained, as reflected by the NMR solution structure, mutating Tyr into Ser at position 15 resulted in substantially reduced PE selectivity. Ala substitution at the same position produced a similar reduction in PE selectivity, while substitution with Phe maintained high selectivity. We conclude that the phenyl ring in Tyr15 is critical for the high PE selectivity of kB7. Our results suggest that PE-binding and divalent cation coordination occur in the same pocket without adverse effects of competitive binding for the phospholipid. PMID:26878982

  12. Broadly neutralizing human antibody that recognizes the receptor-binding pocket of influenza virus hemagglutinin

    Energy Technology Data Exchange (ETDEWEB)

    Whittle, James R.R.; Zhang, Ruijun; Khurana, Surender; King, Lisa R.; Manischewitz, Jody; Golding, Hana; Dormitzer, Philip R.; Haynes, Barton F.; Walter, Emmanuel B.; Moody, M. Anthony; Kepler, Thomas B.; Liao, Hua-Xin; Harrison, Stephen C. (Harvard-Med); (Novartis); (US-FDA); (Duke)

    2011-09-20

    Seasonal antigenic drift of circulating influenza virus leads to a requirement for frequent changes in vaccine composition, because exposure or vaccination elicits human antibodies with limited cross-neutralization of drifted strains. We describe a human monoclonal antibody, CH65, obtained by isolating rearranged heavy- and light-chain genes from sorted single plasma cells, coming from a subject immunized with the 2007 trivalent influenza vaccine. The crystal structure of a complex of the hemagglutinin (HA) from H1N1 strain A/Solomon Islands/3/2006 with the Fab of CH65 shows that the tip of the CH65 heavy-chain complementarity determining region 3 (CDR3) inserts into the receptor binding pocket on HA1, mimicking in many respects the interaction of the physiological receptor, sialic acid. CH65 neutralizes infectivity of 30 out of 36 H1N1 strains tested. The resistant strains have a single-residue insertion near the rim of the sialic-acid pocket. We conclude that broad neutralization of influenza virus can be achieved by antibodies with contacts that mimic those of the receptor.

  13. Evidence for an intrinsic binding force between dodecaborate dianions and receptors with hydrophobic binding pockets.

    Science.gov (United States)

    Warneke, Jonas; Jenne, Carsten; Bernarding, Johannes; Azov, Vladimir A; Plaumann, Markus

    2016-05-01

    A gas phase binding study revealed strong intrinsic intermolecular interactions between dianionic halogenated closo-dodecaborates [B12X12](2-) and several neutral organic receptors. Oxidation of a tetrathiafulvalene host allowed switching between two host-guest binding modes in a supramolecular complex. Complexes of β-cyclodextrin with [B12F12](2-) show remarkable stability in the gas phase and were successfully tested as carriers for the delivery of boron clusters into cancer cells. PMID:27087168

  14. Kinetic evidence for an anion binding pocket in the active site of nitronate monooxygenase.

    Science.gov (United States)

    Francis, Kevin; Gadda, Giovanni

    2009-10-01

    A series of monovalent, inorganic anions and aliphatic aldehydes were tested as inhibitors for Hansenula mrakii and Neurospora crassa nitronate monooxygenase, formerly known as 2-nitropropane dioxygenase, to investigate the structural features that contribute to the binding of the anionic nitronate substrates to the enzymes. A linear correlation between the volumes of the inorganic anions and their effectiveness as competitive inhibitors of the enzymes was observed in a plot of pK(is)versus the ionic volume of the anion with slopes of 0.041+/-0.001 mM/A(3) and 0.027+/-0.001 mM/A(3) for the H. mrakii and N. crassa enzymes, respectively. Aliphatic aldehydes were weak competitive inhibitors of the enzymes, with inhibition constants that are independent of their alkyl chain lengths. The reductive half reactions of H. mrakii nitronate monooxygenase with primary nitronates containing two to four carbon atoms all showed apparent K(d) values of approximately 5 mM. These results are consistent with the presence of an anion binding pocket in the active site of nitronate monooxygenase that interacts with the nitro group of the substrate, and suggest a minimal contribution of the hydrocarbon chain of the nitronates to the binding of the ligands to the enzyme. PMID:19683782

  15. Identification of Glucose-Binding Pockets in Human Serum Albumin Using Support Vector Machine and Molecular Dynamics Simulations.

    Science.gov (United States)

    Ranganarayanan, Preethi; Thanigesan, Narmadha; Ananth, Vivek; Jayaraman, Valadi K; Ramakrishnan, Vigneshwar

    2016-01-01

    Human Serum Albumin (HSA) has been suggested to be an alternate biomarker to the existing Hemoglobin-A1c (HbA1c) marker for glycemic monitoring. Development and usage of HSA as an alternate biomarker requires the identification of glycation sites, or equivalently, glucose-binding pockets. In this work, we combine molecular dynamics simulations of HSA and the state-of-art machine learning method Support Vector Machine (SVM) to predict glucose-binding pockets in HSA. SVM uses the three dimensional arrangement of atoms and their chemical properties to predict glucose-binding ability of a pocket. Feature selection reveals that the arrangement of atoms and their chemical properties within the first 4Å from the centroid of the pocket play an important role in the binding of glucose. With a 10-fold cross validation accuracy of 84 percent, our SVM model reveals seven new potential glucose-binding sites in HSA of which two are exposed only during the dynamics of HSA. The predictions are further corroborated using docking studies. These findings can complement studies directed towards the development of HSA as an alternate biomarker for glycemic monitoring. PMID:26886739

  16. Evolutionary diversification of retinoic acid receptor ligand-binding pocket structure by molecular tinkering.

    Science.gov (United States)

    Gutierrez-Mazariegos, Juliana; Nadendla, Eswar Kumar; Studer, Romain A; Alvarez, Susana; de Lera, Angel R; Kuraku, Shigehiro; Bourguet, William; Schubert, Michael; Laudet, Vincent

    2016-03-01

    Whole genome duplications (WGDs) have been classically associated with the origin of evolutionary novelties and the so-called duplication-degeneration-complementation model describes the possible fates of genes after duplication. However, how sequence divergence effectively allows functional changes between gene duplicates is still unclear. In the vertebrate lineage, two rounds of WGDs took place, giving rise to paralogous gene copies observed for many gene families. For the retinoic acid receptors (RARs), for example, which are members of the nuclear hormone receptor (NR) superfamily, a unique ancestral gene has been duplicated resulting in three vertebrate paralogues: RARα, RARβ and RARγ. It has previously been shown that this single ancestral RAR was neofunctionalized to give rise to a larger substrate specificity range in the RARs of extant jawed vertebrates (also called gnathostomes). To understand RAR diversification, the members of the cyclostomes (lamprey and hagfish), jawless vertebrates representing the extant sister group of gnathostomes, provide an intermediate situation and thus allow the characterization of the evolutionary steps that shaped RAR ligand-binding properties following the WGDs. In this study, we assessed the ligand-binding specificity of cyclostome RARs and found that their ligand-binding pockets resemble those of gnathostome RARα and RARβ. In contrast, none of the cyclostome receptors studied showed any RARγ-like specificity. Together, our results suggest that cyclostome RARs cover only a portion of the specificity repertoire of the ancestral gnathostome RARs and indicate that the establishment of ligand-binding specificity was a stepwise event. This iterative process thus provides a rare example for the diversification of receptor-ligand interactions of NRs following WGDs. PMID:27069642

  17. Comparative study of the binding pockets of mammalian proprotein convertases and its implications for the design of specific small molecule inhibitors

    Directory of Open Access Journals (Sweden)

    Sun Tian, Wu Jianhua

    2010-01-01

    Full Text Available Proprotein convertases are enzymes that proteolytically cleave protein precursors in the secretory pathway to yield functional proteins. Seven mammalian subtilisin/Kex2p-like proprotein convertases have been identified: furin, PC1, PC2, PC4, PACE4, PC5 and PC7. The binding pockets of all seven proprotein convertases are evolutionarily conserved and highly similar. Among the seven proprotein convertases, the furin cleavage site motif has recently been characterized as a 20-residue motif that includes one core region P6-P2´ inside the furin binding pocket. This study extended this information by examining the 3D structural environment of the furin binding pocket surrounding the core region P6-P2´ of furin substrates. The physical properties of mutations in the binding pockets of the other six mammalian proprotein convertases were compared. The results suggest that: 1 mutations at two positions, Glu230 and Glu257, change the overall density of the negative charge of the binding pockets, and govern the substrate specificities of mammalian proprotein convertases; 2 two proprotein convertases (PC1 and PC2 may have reduced sensitivity for positively charged residues at substrate position P5 or P6, whereas the substrate specificities of three proprotein convertases (furin, PACE4, and PC5 are similar to each other. This finding led to a novel design of a short peptide pattern for small molecule inhibitors: [K/R]-X-V-X-K-R. Compared with the widely used small molecule dec-RVKR-cmk that inhibits all seven proprotein convertases, a finely-tuned derivative of the short peptide pattern [K/R]-X-V-X-K-R may have the potential to more effectively inhibit five of the proprotein convertases (furin, PC4, PACE4, PC5 and PC7 compared to the remaining two (PC1 and PC2. The results not only provide insights into the molecular evolution of enzyme function in the proprotein convertase family, but will also aid the study of the functional redundancy of proprotein

  18. Hot spots and transient pockets: predicting the determinants of small-molecule binding to a protein-protein interface.

    Science.gov (United States)

    Metz, Alexander; Pfleger, Christopher; Kopitz, Hannes; Pfeiffer-Marek, Stefania; Baringhaus, Karl-Heinz; Gohlke, Holger

    2012-01-23

    Protein-protein interfaces are considered difficult targets for small-molecule protein-protein interaction modulators (PPIMs ). Here, we present for the first time a computational strategy that simultaneously considers aspects of energetics and plasticity in the context of PPIM binding to a protein interface. The strategy aims at identifying the determinants of small-molecule binding, hot spots, and transient pockets, in a protein-protein interface in order to make use of this knowledge for predicting binding modes of and ranking PPIMs with respect to their affinity. When applied to interleukin-2 (IL-2), the computationally inexpensive constrained geometric simulation method FRODA outperforms molecular dynamics simulations in sampling hydrophobic transient pockets. We introduce the PPIAnalyzer approach for identifying transient pockets on the basis of geometrical criteria only. A sequence of docking to identified transient pockets, starting structure selection based on hot spot information, RMSD clustering and intermolecular docking energies, and MM-PBSA calculations allows one to enrich IL-2 PPIMs from a set of decoys and to discriminate between subgroups of IL-2 PPIMs with low and high affinity. Our strategy will be applicable in a prospective manner where nothing else than a protein-protein complex structure is known; hence, it can well be the first step in a structure-based endeavor to identify PPIMs. PMID:22087639

  19. Structures of BmrR-Drug Complexes Reveal a Rigid Multidrug Binding Pocket And Transcription Activation Through Tyrosine Expulsion

    Energy Technology Data Exchange (ETDEWEB)

    Newberry, K.J.; Huffman, J.L.; Miller, M.C.; Vazquez-Laslop, N.; Neyfakh, A.A.; Brennan, R.G.

    2009-05-22

    BmrR is a member of the MerR family and a multidrug binding transcription factor that up-regulates the expression of the bmr multidrug efflux transporter gene in response to myriad lipophilic cationic compounds. The structural mechanism by which BmrR binds these chemically and structurally different drugs and subsequently activates transcription is poorly understood. Here, we describe the crystal structures of BmrR bound to rhodamine 6G (R6G) or berberine (Ber) and cognate DNA. These structures reveal each drug stacks against multiple aromatic residues with their positive charges most proximal to the carboxylate group of Glu-253 and that, unlike other multidrug binding pockets, that of BmrR is rigid. Substitution of Glu-253 with either alanine (E253A) or glutamine (E253Q) results in unpredictable binding affinities for R6G, Ber, and tetraphenylphosphonium. Moreover, these drug binding studies reveal that the negative charge of Glu-253 is not important for high affinity binding to Ber and tetraphenylphosphonium but plays a more significant, but unpredictable, role in R6G binding. In vitro transcription data show that E253A and E253Q are constitutively active, and structures of the drug-free E253A-DNA and E253Q-DNA complexes support a transcription activation mechanism requiring the expulsion of Tyr-152 from the multidrug binding pocket. In sum, these data delineate the mechanism by which BmrR binds lipophilic, monovalent cationic compounds and suggest the importance of the redundant negative electrostatic nature of this rigid drug binding pocket that can be used to discriminate against molecules that are not substrates of the Bmr multidrug efflux pump.

  20. An induced pocket for the binding of potent fusion inhibitor CL-385319 with H5N1 influenza virus hemagglutinin.

    Directory of Open Access Journals (Sweden)

    Runming Li

    Full Text Available The influenza glycoprotein hemagglutinin (HA plays crucial roles in the early stage of virus infection, including receptor binding and membrane fusion. Therefore, HA is a potential target for developing anti-influenza drugs. Recently, we characterized a novel inhibitor of highly pathogenic H5N1 influenza virus, CL-385319, which specifically inhibits HA-mediated viral entry. Studies presented here identified the critical binding residues for CL-385319, which clustered in the stem region of the HA trimer by site-directed mutagenesis. Extensive computational simulations, including molecular docking, molecular dynamics simulations, molecular mechanics generalized Born surface area (MM_GBSA calculations, charge density and Laplacian calculations, have been carried out to uncover the detailed molecular mechanism that underlies the binding of CL-385319 to H5N1 influenza virus HA. It was found that the recognition and binding of CL-385319 to HA proceeds by a process of "induced fit" whereby the binding pocket is formed during their interaction. Occupation of this pocket by CL-385319 stabilizes the neutral pH structure of hemagglutinin, thus inhibiting the conformational rearrangements required for membrane fusion. This "induced fit" pocket may be a target for structure-based design of more potent influenza fusion inhibitors.

  1. Reshaping an enzyme binding pocket for enhanced and inverted stereoselectivity: use of smallest amino acid alphabets in directed evolution.

    Science.gov (United States)

    Sun, Zhoutong; Lonsdale, Richard; Kong, Xu-Dong; Xu, Jian-He; Zhou, Jiahai; Reetz, Manfred T

    2015-10-12

    Directed evolution based on saturation mutagenesis at sites lining the binding pocket is a commonly practiced strategy for enhancing or inverting the stereoselectivity of enzymes for use in organic chemistry or biotechnology. However, as the number of residues in a randomization site increases to five or more, the screening effort for 95 % library coverage increases astronomically until it is no longer feasible. We propose the use of a single amino acid for saturation mutagenesis at superlarge randomization sites comprising 10 or more residues. When used to reshape the binding pocket of limonene epoxide hydrolase, this strategy, which drastically reduces the search space and thus the screening effort, resulted in R,R- and S,S-selective mutants for the hydrolytic desymmetrization of cyclohexene oxide and other epoxides. X-ray crystal structures and docking studies of the mutants unveiled the source of stereoselectivity and shed light on the mechanistic intricacies of this enzyme. PMID:25891639

  2. Drug Promiscuity in PDB: Protein Binding Site Similarity Is Key.

    Directory of Open Access Journals (Sweden)

    V Joachim Haupt

    Full Text Available Drug repositioning applies established drugs to new disease indications with increasing success. A pre-requisite for drug repurposing is drug promiscuity (polypharmacology - a drug's ability to bind to several targets. There is a long standing debate on the reasons for drug promiscuity. Based on large compound screens, hydrophobicity and molecular weight have been suggested as key reasons. However, the results are sometimes contradictory and leave space for further analysis. Protein structures offer a structural dimension to explain promiscuity: Can a drug bind multiple targets because the drug is flexible or because the targets are structurally similar or even share similar binding sites? We present a systematic study of drug promiscuity based on structural data of PDB target proteins with a set of 164 promiscuous drugs. We show that there is no correlation between the degree of promiscuity and ligand properties such as hydrophobicity or molecular weight but a weak correlation to conformational flexibility. However, we do find a correlation between promiscuity and structural similarity as well as binding site similarity of protein targets. In particular, 71% of the drugs have at least two targets with similar binding sites. In order to overcome issues in detection of remotely similar binding sites, we employed a score for binding site similarity: LigandRMSD measures the similarity of the aligned ligands and uncovers remote local similarities in proteins. It can be applied to arbitrary structural binding site alignments. Three representative examples, namely the anti-cancer drug methotrexate, the natural product quercetin and the anti-diabetic drug acarbose are discussed in detail. Our findings suggest that global structural and binding site similarity play a more important role to explain the observed drug promiscuity in the PDB than physicochemical drug properties like hydrophobicity or molecular weight. Additionally, we find ligand

  3. Mutations in FMN Binding Pocket Diminish Chromate Reduction Rates for Gh-ChrR Isolated from Gluconacetobacter hansenii

    Energy Technology Data Exchange (ETDEWEB)

    Khaleel, Janin A.; Gong, Chunhong; Zhang, Yanfeng; Tan, Ruimin; Squier, Thomas C.; Jin, Hongjun

    2013-06-01

    A putative chromate ion binding site was identified proximal to a rigidly bound FMN from electron densities in the crystal structure of the quinone reductase from Gluconacetobacter hansenii (Gh-ChrR) (3s2y.pdb). To clarify the location of the chromate binding site, and to understand the role of FMN in the NADPH-dependent reduction of chromate, we have expressed and purified four mutant enzymes involving the site-specific substitution of individual side chains within the FMN binding pocket that form non-covalent bonds with the ribityl phosphate (i.e., S15A and R17A in loop 1 between β1 sheet and α1 helix) or the isoalloxanzine ring (E83A or Y84A in loop 4 between the β3 sheet and α4 helix). Mutations that selectively disrupt hydrogen bonds between either the N3 nitrogen on the isoalloxanzine ring (i.e., E83) or the ribitylphos- phoate (i.e., S15) respectively result in 50% or 70% reductions in catalytic rates of chromate reduction. In comparison, mutations that disrupt π-π ring stacking interactions with the isoal-loxanzine ring (i.e., Y84) or a salt bridge with the ribityl phosphate result in 87% and 97% inhibittion. In all cases there are minimal alterations in chromate binding affinities. Collectively, these results support the hypothesis that chromate binds proximal to FMN, and implicate a structural role for FMN positioning for optimal chromate reduction rates. As side chains proximal to the β3/α4 FMN binding loop 4 contribute to both NADH and metal ion binding, we propose a model in which structural changes around the FMN binding pocket couples to both chromate and NADH binding sites.

  4. Structural and mechanistic investigations on Salmonella typhimurium acetate kinase (AckA: identification of a putative ligand binding pocket at the dimeric interface

    Directory of Open Access Journals (Sweden)

    Chittori Sagar

    2012-10-01

    Full Text Available Abstract Background Bacteria such as Escherichia coli and Salmonella typhimurium can utilize acetate as the sole source of carbon and energy. Acetate kinase (AckA and phosphotransacetylase (Pta, key enzymes of acetate utilization pathway, regulate flux of metabolites in glycolysis, gluconeogenesis, TCA cycle, glyoxylate bypass and fatty acid metabolism. Results Here we report kinetic characterization of S. typhimurium AckA (StAckA and structures of its unliganded (Form-I, 2.70 Å resolution and citrate-bound (Form-II, 1.90 Å resolution forms. The enzyme showed broad substrate specificity with kcat/Km in the order of acetate > propionate > formate. Further, the Km for acetyl-phosphate was significantly lower than for acetate and the enzyme could catalyze the reverse reaction (i.e. ATP synthesis more efficiently. ATP and Mg2+ could be substituted by other nucleoside 5′-triphosphates (GTP, UTP and CTP and divalent cations (Mn2+ and Co2+, respectively. Form-I StAckA represents the first structural report of an unliganded AckA. StAckA protomer consists of two domains with characteristic βββαβαβα topology of ASKHA superfamily of proteins. These domains adopt an intermediate conformation compared to that of open and closed forms of ligand-bound Methanosarcina thermophila AckA (MtAckA. Spectroscopic and structural analyses of StAckA further suggested occurrence of inter-domain motion upon ligand-binding. Unexpectedly, Form-II StAckA structure showed a drastic change in the conformation of residues 230–300 compared to that of Form-I. Further investigation revealed electron density corresponding to a citrate molecule in a pocket located at the dimeric interface of Form-II StAckA. Interestingly, a similar dimeric interface pocket lined with largely conserved residues could be identified in Form-I StAckA as well as in other enzymes homologous to AckA suggesting that ligand binding at this pocket may influence the function of these

  5. Aromatic Amino Acid Mutagenesis at the Substrate Binding Pocket of Yarrowia lipolytica Lipase Lip2 Affects Its Activity and Thermostability

    OpenAIRE

    Guilong Wang; Zimin Liu; Li Xu; Yunjun Yan

    2014-01-01

    The lipase2 from Yarrowia lipolytica (YLLip2) is a yeast lipase exhibiting high homologous to filamentous fungal lipase family. Though its crystal structure has been resolved, its structure-function relationship has rarely been reported. By contrast, there are two amino acid residues (V94 and I100) with significant difference in the substrate binding pocket of YLLip2; they were subjected to site-directed mutagenesis (SDM) to introduce aromatic amino acid mutations. Two mutants (V94W and I100F...

  6. Identification of an alternative ligand-binding pocket in the nuclear vitamin D receptor and its functional importance in 1α,25(OH)2-vitamin D3 signaling

    OpenAIRE

    Mizwicki, Mathew T; Keidel, Don; Bula, Craig M.; Bishop, June. E.; Zanello, Laura P; Wurtz, Jean-Marie; Moras, Dino; Norman, Anthony W.

    2004-01-01

    Structural and molecular studies have shown that the vitamin D receptor (VDR) mediates 1α,25(OH)2-vitamin D3 gene transactivation. Recent evidence indicates that both VDR and the estrogen receptor are localized to plasma membrane caveolae and are required for initiation of nongenomic (NG) responses. Computer docking of the NG-specific 1α,25(OH)2-lumisterol to the VDR resulted in identification of an alternative ligand-binding pocket that partially overlaps the genomic pocket described in the ...

  7. A molecular description of ligand binding to the two overlapping binding pockets of the nuclear vitamin D receptor (VDR): structure-function implications

    OpenAIRE

    Mizwicki, Mathew T; Menegaz, Danusa; Yaghmaei, Sepideh; Henry, Helen L.; Norman, Anthony W.

    2010-01-01

    Molecular modeling results indicate that the VDR contains two overlapping ligand binding pockets (LBP). Differential ligand stability and fractional occupancy of the two LBP has been physiochemically linked to the regulation of VDR-dependent genomic and non-genomic cellular responses. The purpose of this report is to develop an unbiased molecular modeling protocol that serves as a good starting point in simulating the dynamic interaction between 1α,25(OH)2-vitamin D3 (1,25D3) and the VDR LBP....

  8. Fatty Acid- and Retinoid-binding Proteins Have Distinct Binding Pockets for the Two Types of Cargo*

    OpenAIRE

    Jordanova, Rositsa; Groves, Matthew R.; Kostova, Elena; Woltersdorf, Christian; Liebau, Eva; Tucker, Paul A.

    2009-01-01

    Parasitic nematodes cause serious diseases in humans, animals, and plants. They have limited lipid metabolism and are reliant on lipid-binding proteins to acquire these metabolites from their hosts. Several structurally novel families of lipid-binding proteins in nematodes have been described, including the fatty acid- and retinoid-binding protein family (FAR). In Caenorhabditis elegans, used as a model for studying parasitic nematodes, eight C. elegans FAR proteins have been described. The c...

  9. Sequence similarity between the erythrocyte binding domain 1 of the Plasmodium vivax Duffy binding protein and the V3 loop of HIV-1 strain MN reveals binding residues for the Duffy Antigen Receptor for Chemokines

    Directory of Open Access Journals (Sweden)

    Garry Robert F

    2011-01-01

    Full Text Available Abstract Background The surface glycoprotein (SU, gp120 of the human immunodeficiency virus (HIV must bind to a chemokine receptor, CCR5 or CXCR4, to invade CD4+ cells. Plasmodium vivax uses the Duffy Binding Protein (DBP to bind the Duffy Antigen Receptor for Chemokines (DARC and invade reticulocytes. Results Variable loop 3 (V3 of HIV-1 SU and domain 1 of the Plasmodium vivax DBP share a sequence similarity. The site of amino acid sequence similarity was necessary, but not sufficient, for DARC binding and contained a consensus heparin binding site essential for DARC binding. Both HIV-1 and P. vivax can be blocked from binding to their chemokine receptors by the chemokine, RANTES and its analog AOP-RANTES. Site directed mutagenesis of the heparin binding motif in members of the DBP family, the P. knowlesi alpha, beta and gamma proteins abrogated their binding to erythrocytes. Positively charged residues within domain 1 are required for binding of P. vivax and P. knowlesi erythrocyte binding proteins. Conclusion A heparin binding site motif in members of the DBP family may form part of a conserved erythrocyte receptor binding pocket.

  10. Exploring the binding nature of pyrrolidine pocket-dependent interactions in the polo-box domain of polo-like kinase 1.

    Directory of Open Access Journals (Sweden)

    Ravichandran N Murugan

    Full Text Available BACKGROUND: Over the years, a great deal of effort has been focused on the design and synthesis of potent, linear peptide inhibitors targeting the polo-like kinase 1 (Plk1, which is critically involved in multiple mitotic processes and has been established as an adverse prognostic marker for tumor patients. Plk1 localizes to its intracellular anchoring sites via its polo-box domain, and inhibiting the Plk1 polo-box domain has been considered as an approach to circumvent the specificity problems associated with inhibiting the conserved adenosine triphosphate-binding pocket. The polo-box domain consists of two different binding regions, such as the unique, broader pyrrolidine-binding pocket and the conserved, narrow, Tyr-rich hydrophobic channel, among the three Plk polo-box domains (Plks 1-3, respectively. Therefore, the studies that provide insights into the binding nature of the unique, broader pyrrolidine-binding pocket might lead to the development of selective Plk1-inhibitory compounds. METHODOLOGY/PRINCIPAL FINDINGS: In an attempt to retain the monospecificity by targeting the unique, broader pyrrolidine-binding pocket, here, for the first time, a systematic approach was undertaken to examine the structure-activity relationship of N-terminal-truncated PLHSpTM derivatives, to apply a site-directed ligand approach using bulky aromatic and non-aromatic systems, and to characterize the binding nature of these analogues using X-ray crystallographic studies. We have identified a new mode of binding interactions, having improved binding affinity and retaining the Plk1 polo-box domain specificity, at the pyrrolidine-binding pocket. Furthermore, our data revealed that the pyrrolidine-binding pocket was very specific to recognize a short and bulky hydrophobic ligand like adamantane, whereas the Tyr-rich hydrophobic channel was specific with lengthy and small hydrophobic groups. CONCLUSION/SIGNIFICANCE: The progress made using our site

  11. Post-docking virtual screening of diverse binding pockets: comparative study using DOCK, AMMOS, X-Score and FRED scoring functions.

    Science.gov (United States)

    Pencheva, Tania; Soumana, Oumarou Samna; Pajeva, Ilza; Miteva, Maria A

    2010-06-01

    Most of the benchmark studies on docking-scoring methods reported in the last decade conclude that no single scoring function performs well across different protein targets. In this study a comparison of thirteen commonly used force field and empirical scoring functions as implemented in DOCK, AMMOS, X-Score and FRED is carried out on five proteins with diverse binding pockets. The performance is analyzed in relation to the physicochemical properties of the binding sites. The solvation effects are considered via the Generalized Born/Surface Area (GBSA) solvation method for one of the assessed scoring functions. We examined the ability of these scoring functions to discriminate between active and inactive compounds over receptor-based focused libraries. Our results demonstrated that the employed here empirical scoring functions were more appropriate for the pocket of predominant hydrophobic nature while the force field scoring functions performed better on the mixed or polar pockets. PMID:20227800

  12. A New Method for Navigating Optimal Direction for Pulling Ligand from Binding Pocket: Application to Ranking Binding Affinity by Steered Molecular Dynamics.

    Science.gov (United States)

    Vuong, Quan Van; Nguyen, Tin Trung; Li, Mai Suan

    2015-12-28

    In this paper we present a new method for finding the optimal path for pulling a ligand from the binding pocket using steered molecular dynamics (SMD). Scoring function is defined as the steric hindrance caused by a receptor to ligand movement. Then the optimal path corresponds to the minimum of this scoring function. We call the new method MSH (Minimal Steric Hindrance). Contrary to existing navigation methods, our approach takes into account the geometry of the ligand while other methods including CAVER only consider the ligand as a sphere with a given radius. Using three different target + receptor sets, we have shown that the rupture force Fmax and nonequilibrium work Wpull obtained based on the MSH method show a much higher correlation with experimental data on binding free energies compared to CAVER. Furthermore, Wpull was found to be a better indicator for binding affinity than Fmax. Thus, the new MSH method is a reliable tool for obtaining the best direction for ligand exiting from the binding site. Its combination with the standard SMD technique can provide reasonable results for ranking binding affinities using Wpull as a scoring function. PMID:26595261

  13. Electrostatic Modifications of the Human Leukocyte Antigen-DR P9 Peptide-Binding Pocket and Susceptibility to Primary Sclerosing Cholangitis

    Science.gov (United States)

    Hov, Johannes R; Kosmoliaptsis, Vasilis; Traherne, James A; Olsson, Marita; Boberg, Kirsten M; Bergquist, Annika; Schrumpf, Erik; Bradley, J Andrew; Taylor, Craig J; Lie, Benedicte A; Trowsdale, John; Karlsen, Tom H

    2011-01-01

    The strongest genetic risk factors for primary sclerosing cholangitis (PSC) are found in the human leukocyte antigen (HLA) complex at chromosome 6p21. Genes in the HLA class II region encode molecules that present antigen to T lymphocytes. Polymorphisms in these genes are associated with most autoimmune diseases, most likely because they contribute to the specificity of immune responses. The aim of this study was to analyze the structure and electrostatic properties of the peptide-binding groove of HLA-DR in relation to PSC. Thus, four-digit resolution HLA-DRB1 genotyping was performed in 356 PSC patients and 366 healthy controls. Sequence information was used to assign which amino acids were encoded at all polymorphic positions. In stepwise logistic regressions, variations at residues 37 and 86 were independently associated with PSC (P = 1.2 × 10−32 and P = 1.8 × 10−22 in single-residue models, respectively). Three-dimensional modeling was performed to explore the effect of these key residues on the HLA-DR molecule. This analysis indicated that residue 37 was a major determinant of the electrostatic properties of pocket P9 of the peptide-binding groove. Asparagine at residue 37, which was associated with PSC, induced a positive charge in pocket P9. Tyrosine, which protected against PSC, induced a negative charge in this pocket. Consistent with the statistical observations, variation at residue 86 also indirectly influenced the electrostatic properties of this pocket. DRB1*13:01, which was PSC-associated, had a positive P9 pocket and DRB1*13:02, protective against PSC, had a negative P9 pocket. Conclusion: The results suggest that in patients with PSC, residues 37 and 86 of the HLA-DRβ chain critically influence the electrostatic properties of pocket P9 and thereby the range of peptides presented. (Hepatology 2011;53:1967-1976) PMID:21413052

  14. Aromatic Amino Acid Mutagenesis at the Substrate Binding Pocket of Yarrowia lipolytica Lipase Lip2 Affects Its Activity and Thermostability

    Directory of Open Access Journals (Sweden)

    Guilong Wang

    2014-01-01

    Full Text Available The lipase2 from Yarrowia lipolytica (YLLip2 is a yeast lipase exhibiting high homologous to filamentous fungal lipase family. Though its crystal structure has been resolved, its structure-function relationship has rarely been reported. By contrast, there are two amino acid residues (V94 and I100 with significant difference in the substrate binding pocket of YLLip2; they were subjected to site-directed mutagenesis (SDM to introduce aromatic amino acid mutations. Two mutants (V94W and I100F were created. The enzymatic properties of the mutant lipases were detected and compared with the wild-type. The activities of mutant enzymes dropped to some extent towards p-nitrophenyl palmitate (pNPC16 and their optimum temperature was 35°C, which was 5°C lower than that of the wild-type. However, the thermostability of I100F increased 22.44% after incubation for 1 h at 40°C and its optimum substrate shifted from p-nitrophenyl laurate (pNPC12 to p-nitrophenyl caprate (pNPC10. The above results demonstrated that the two substituted amino acid residuals have close relationship with such enzymatic properties as thermostability and substrate selectivity.

  15. Study on the Gas Phase Stability of Heme-binding Pocket in Cytochrome Tb5 and Its Mutants by Electrospray Mass Spectrometry

    Institute of Scientific and Technical Information of China (English)

    YU,Chong-Tian(余翀天); GUO,Yin-Long(郭寅龙); L(U),Long(吕龙); WANG,Yun-Hua(王韵华); YAO,Ping(姚萍); HUANG,Zhong-Xian(黄仲贤)

    2002-01-01

    To ehucidate the effect of various amino acid residues on the heme-binding pocket in cytochrome Tbs, several residues were chosen for replacement by means of site-directed mutagenesis.Comparison of the mass spectrmn between the F35Y mutant and the wild type shows that the relative abundance of holoprotein ion of F35Y is lower than that of the wild type in gas phase. It is concluded that mutation from Phe35 residue to tyrosine decreases the hydrophobic character of cytochrome Tbs heme pocket, which decreases the stability of heme-binding pocket. ESI-MS spectra of the mutants V61E, V61K, V61H and V61Y show various contribution of amino acid to the stability of heme-binding pocket. The small and non-polar residue Vat61 was replaced with large or polar residues, resulting in enhancing the trend of heme leaving from the pocket. In addition, comparison of the mass relative abundance of bolo-proteins among all the Va161-mutants, shows that their stability in gas phase appropriately submit the following order: wild type > V61H > V61E > V61K ≈ V61Y. The extra great stability of quadruple sites mutant E44/48/56A/D60A shows that reduction of electrostatic or hydrogen bond interactions among the residues locating in the outside region of the heme edge remarkably affect the stability of heme. The results of analyzing the oxidation states of heme iron in Tbs and its mutants by insource-CAD experiment suggest that the charge states of heme iron maintain inflexible in mutation process.

  16. Pocket Money

    Institute of Scientific and Technical Information of China (English)

    刘杰莹; 赵惠; 李世芹; 袁琳

    2007-01-01

    Do you get any poch’et money from your parents? What do you do with it?刘杰莹Pocket Money (1st Floor) I get some pocket money from Mom every day.But I never spend it casually.Except the money for breakfast,

  17. A minimal ligand binding pocket within a network of correlated mutations identified by multiple sequence and structural analysis of G protein coupled receptors

    International Nuclear Information System (INIS)

    G protein coupled receptors (GPCRs) are seven helical transmembrane proteins that function as signal transducers. They bind ligands in their extracellular and transmembrane regions and activate cognate G proteins at their intracellular surface at the other side of the membrane. The relay of allosteric communication between the ligand binding site and the distant G protein binding site is poorly understood. In this study, GREMLIN, a recently developed method that identifies networks of co-evolving residues from multiple sequence alignments, was used to identify those that may be involved in communicating the activation signal across the membrane. The GREMLIN-predicted long-range interactions between amino acids were analyzed with respect to the seven GPCR structures that have been crystallized at the time this study was undertaken. We demonstrate the use of GREMLIN to reveal a network of statistically correlated and functionally important residues in class A GPCRs. GREMLIN identified that ligand binding pocket residues are extensively correlated with distal residues. An analysis of the GREMLIN edges across multiple structures suggests that there may be a minimal binding pocket common to the seven known GPCRs. Further, the activation of rhodopsin involves these long-range interactions between extracellular and intracellular domain residues mediated by the retinal domain.

  18. Engineered tryptophan in the adenine-binding pocket of catalytic subunit A of A-ATP synthase demonstrates the importance of aromatic residues in adenine binding, forming a tool for steady-state and time-resolved fluorescence spectroscopy

    International Nuclear Information System (INIS)

    The crystallographic structures of the subunit B mutants F427W and F508W of the Pyrococcus horikoshii OT3 of the A1AO ATP synthase reveal that the exact volume of the adenine ribose binding pocket is essential for ATP-/ADP-binding. A reporter tryptophan residue was individually introduced by site-directed mutagenesis into the adenine-binding pocket of the catalytic subunit A (F427W and F508W mutants) of the motor protein A1AO ATP synthase from Pyrococcus horikoshii OT3. The crystal structures of the F427W and F508W mutant proteins were determined to 2.5 and 2.6 Å resolution, respectively. The tryptophan substitution caused the fluorescence signal to increase by 28% (F427W) and 33% (F508W), with a shift from 333 nm in the wild-type protein to 339 nm in the mutant proteins. Tryptophan emission spectra showed binding of Mg-ATP to the F427W mutant with a Kd of 8.5 µM. In contrast, no significant binding of nucleotide could be observed for the F508W mutant. A closer inspection of the crystal structure of the F427W mutant showed that the adenine-binding pocket had widened by 0.7 Å (to 8.70 Å) in comparison to the wild-type subunit A (8.07 Å) owing to tryptophan substitution, as a result of which it was able to bind ATP. In contrast, the adenine-binding pocket had narrowed in the F508W mutant. The two mutants presented demonstrate that the exact volume of the adenine ribose binding pocket is essential for nucleotide binding and even minor narrowing makes it unfit for nucleotide binding. In addition, structural and fluorescence data confirmed the viability of the fluorescently active mutant F427W, which had ideal tryptophan spectra for future structure-based time-resolved dynamic measurements of the catalytic subunit A of the ATP-synthesizing enzyme A-ATP synthase

  19. Probing the Binding Pocket of the Broadly Tuned Human Bitter Taste Receptor TAS2R14 by Chemical Modification of Cognate Agonists.

    Science.gov (United States)

    Karaman, Rafik; Nowak, Stefanie; Di Pizio, Antonella; Kitaneh, Hothaifa; Abu-Jaish, Alaa; Meyerhof, Wolfgang; Niv, Masha Y; Behrens, Maik

    2016-07-01

    Sensing potentially harmful bitter substances in the oral cavity is achieved by a group of (˜) 25 receptors, named TAS2Rs, which are expressed in specialized sensory cells and recognize individual but overlapping sets of bitter compounds. The receptors differ in their tuning breadths ranging from narrowly to broadly tuned receptors. One of the most broadly tuned human bitter taste receptors is the TAS2R14 recognizing an enormous variety of chemically diverse synthetic and natural bitter compounds, including numerous medicinal drugs. This suggests that this receptor possesses a large readily accessible ligand binding pocket. To allow probing the accessibility and size of the ligand binding pocket, we chemically modified cognate agonists and tested receptor responses in functional assays. The addition of large functional groups to agonists was usually possible without abolishing agonistic activity. The newly synthesized agonist derivatives were modeled in the binding site of the receptor, providing comparison to the mother substances and rationalization of the in vitro activities of this series of compounds. PMID:26825540

  20. Targeting the Small- and Intermediate-Conductance Ca2+-Activated Potassium Channels: The Drug-Binding Pocket at the Channel/Calmodulin Interface

    Directory of Open Access Journals (Sweden)

    Meng Cui

    2014-10-01

    Full Text Available The small- and intermediate-conductance Ca2+-activated potassium (SK/IK channels play important roles in the regulation of excitable cells in both the central nervous and cardiovascular systems. Evidence from animal models has implicated SK/IK channels in neurological conditions such as ataxia and alcohol use disorders. Further, genome-wide association studies have suggested that cardiovascular abnormalities such as arrhythmias and hypertension are associated with single nucleotide polymorphisms that occur within the genes encoding the SK/IK channels. The Ca2+ sensitivity of the SK/IK channels stems from a constitutively bound Ca2+-binding protein: calmodulin. Small-molecule positive modulators of SK/IK channels have been developed over the past decade, and recent structural studies have revealed that the binding pocket of these positive modulators is located at the interface between the channel and calmodulin. SK/IK channel positive modulators can potentiate channel activity by enhancing the coupling between Ca2+ sensing via calmodulin and mechanical opening of the channel. Here, we review binding pocket studies that have provided structural insight into the mechanism of action for SK/IK channel positive modulators. These studies lay the foundation for structure-based drug discovery efforts that can identify novel SK/IK channel positive modulators. © 2014 S. Karger AG, Basel

  1. Pocket Bikes

    Institute of Scientific and Technical Information of China (English)

    Terry Mccarthy; 陈青

    2004-01-01

    @@ The next big thing out of California is 18 in. High, weighs about 50 lbs. And is capable of traveling up to 70 m. P. H. Meet the pocket bike, a scaled-down①motorcycle that is selling faster than low-carb hot cakes across the Golden State②-and causing nightmares③ for traffic police.

  2. Binding of Similarly Charged Plates: A Global Analysis

    OpenAIRE

    Moreira, Andre G.; Netz, Roland R.

    2000-01-01

    Similarly and highly charged plates in the presence of multivalent counter ions attract each other, leading to electrostatically bound states. Using Monte-Carlo simulations we obtain the inter-plate pressure in the global parameter space. The equilibrium plate separation, where the pressure changes from attractive to repulsive, exhibits a novel unbinding transition. A systematic and asymptotically exact strong-coupling field-theory yields the bound state from a competition between counter-ion...

  3. Protein PocketViewer: A Web-Service Based Interface for Protein Pocket Extraction and Visualization

    OpenAIRE

    Xiaoyu Zhang; Martin Gordon

    2013-01-01

    One important problem in bioinformatics is to study pockets or tunnels within the protein structure. These pocket or tunnel regions are significant because they indicate areas of ligand binding or enzymatic reactions, and tunnels are often solvent ion conductance areas. The Protein Pocket Viewer (PPV) is a web interface that allows the user to extract and visualize the protein pockets in a browser, based on the algorithm in [1]. The PPV packaged the pocket extraction executable as a web servi...

  4. Isolation of a Thiamine-binding Protein from Rice Germ and Distribution of Similar Proteins.

    Science.gov (United States)

    Shimizu, M; Yoshida, T; Toda, T; Iwashima, A; Mitsunaga, T

    1996-01-01

    A thiamine-binding protein was purified from rice germ (Oryza sativa L.) by extraction, salting-out with ammonium sulfate, and column chromatography. From the results of molecular mass, Kd and Bmax values for thiamine-binding, binding specificity for thiamine phosphates and analog, the protein was suggested to be identical to the thiamine-binding protein in rice bran. The thiamine-binding protein w as more efficiently purified from rice germ than from rice bran. The protein was rich in glutamic acid (and/or glutamine) and glycine. The protein did not show immunological similarity to thiamine-binding proteins in buckwheat and sesame seeds. However proteins similar to the thiamine-binding protein from rice germ existed in gramineous seeds. They were suggested to have thiamine-binding activity and to be of the same molecular mass as the thiamine-binding protein. PMID:27299548

  5. Pathogenicity of the BRCA1 Missense Variant M1775K is Determined by the Disruption of the BRCT Phosphopeptide-Binding Pocket: a Multi-Modal Approach

    Energy Technology Data Exchange (ETDEWEB)

    Tischkowitz,M.; Hamel, N.; Carvalho, M.; Birrane, G.; Soni, A.; van Beers, E.; Joosse, S.; Wong, N.; Novak, D.; et al

    2008-01-01

    A number of germ-line mutations in the BRCA1 gene confer susceptibility to breast and ovarian cancer. However, it remains difficult to determine whether many single amino-acid (missense) changes in the BRCA1 protein that are frequently detected in the clinical setting are pathologic or not. Here, we used a combination of functional, crystallographic, biophysical, molecular and evolutionary techniques, and classical genetic segregation analysis to demonstrate that the BRCA1 missense variant M1775K is pathogenic. Functional assays in yeast and mammalian cells showed that the BRCA1 BRCT domains carrying the amino-acid change M1775K displayed markedly reduced transcriptional activity, indicating that this variant represents a deleterious mutation. Importantly, the M1775K mutation disrupted the phosphopeptide-binding pocket of the BRCA1 BRCT domains, thereby inhibiting the BRCA1 interaction with the proteins BRIP1 and CtIP, which are involved in DNA damage-induced checkpoint control. These results indicate that the integrity of the BRCT phosphopeptide-binding pocket is critical for the tumor suppression function of BRCA1. Moreover, this study demonstrates that multiple lines of evidence obtained from a combination of functional, structural, molecular and evolutionary techniques, and classical genetic segregation analysis are required to confirm the pathogenicity of rare variants of disease-susceptibility genes and obtain important insights into the underlying pathogenetic mechanisms.

  6. Mutational analysis of the binding pockets of the diketo acid inhibitor L-742,001 in the influenza virus PA endonuclease.

    Science.gov (United States)

    Stevaert, Annelies; Dallocchio, Roberto; Dessì, Alessandro; Pala, Nicolino; Rogolino, Dominga; Sechi, Mario; Naesens, Lieve

    2013-10-01

    The influenza virus PA endonuclease, which cleaves capped host pre-mRNAs to initiate synthesis of viral mRNA, is a prime target for antiviral therapy. The diketo acid compound L-742,001 was previously identified as a potent inhibitor of the influenza virus endonuclease reaction, but information on its precise binding mode to PA or potential resistance profile is limited. Computer-assisted docking of L-742,001 into the crystal structure of inhibitor-free N-terminal PA (PA-Nter) indicated a binding orientation distinct from that seen in a recent crystallographic study with L-742,001-bound PA-Nter (R. M. DuBois et al., PLoS Pathog. 8:e1002830, 2012). A comprehensive mutational analysis was performed to determine which amino acid changes within the catalytic center of PA or its surrounding hydrophobic pockets alter the antiviral sensitivity to L-742,001 in cell culture. Marked (up to 20-fold) resistance to L-742,001 was observed for the H41A, I120T, and G81F/V/T mutant forms of PA. Two- to 3-fold resistance was seen for the T20A, L42T, and V122T mutants, and the R124Q and Y130A mutants were 3-fold more sensitive to L-742,001. Several mutations situated at noncatalytic sites in PA had no or only marginal impact on the enzymatic functionality of viral ribonucleoprotein complexes reconstituted in cell culture, consistent with the less conserved nature of these PA residues. Our data provide relevant insights into the binding mode of L-742,001 in the PA endonuclease active site. In addition, we predict some potential resistance sites that should be taken into account during optimization of PA endonuclease inhibitors toward tight binding in any of the hydrophobic pockets surrounding the catalytic center of the enzyme. PMID:23824822

  7. Auxin-binding pocket of ABP1 is crucial for its gain-of-function cellular and developmental roles

    Czech Academy of Sciences Publication Activity Database

    Grones, P.; Chen, X.; Simon, S.; Kaufmann, W.A.; De Rycke, R.; Nodzyński, T.; Zažímalová, Eva; Friml, J.

    2015-01-01

    Roč. 66, č. 16 (2015), s. 5055-5065. ISSN 0022-0957 Institutional support: RVO:61389030 Keywords : Auxin * ABP1 * Auxin binding Subject RIV: EB - Genetic s ; Molecular Biology Impact factor: 5.526, year: 2014

  8. Antibody remodeling: a general solution to the design of a metal-coordination site in an antibody binding pocket.

    OpenAIRE

    Roberts, V A; Iverson, B L; Iverson, S A; Benkovic, S J; Lerner, R A; Getzoff, E D; Tainer, J A

    1990-01-01

    To develop a general approach to designing cofactor-binding sites for catalytic antibodies, we characterized structural patterns in the binding sites of antibodies and zinc enzymes. Superposition of eight sets of antibody light- and heavy-chain variable domains identified structurally conserved sites within the sequence-variable complementarity determining regions. The pattern for catalytic zinc sites included two ligands close in sequence, a sequence-distant ligand, and a main-chain hydrogen...

  9. Two types of antibodies are induced by vaccination with A/California/2009 pdm virus: binding near the sialic acid-binding pocket and neutralizing both H1N1 and H5N1 viruses.

    Directory of Open Access Journals (Sweden)

    Nobuko Ohshima

    Full Text Available Many people have a history of catching the flu several times during childhood but no additional flu in adulthood, even without vaccination. We analyzed the total repertoire of antibodies (Abs against influenza A group 1 viruses induced in such a flu-resistant person after vaccination with 2009 H1N1 pandemic influenza virus. They were classified into two types, with no exceptions. The first type, the products of B cells newly induced through vaccination, binds near the sialic acid-binding pocket. The second type, the products of long-lived memory B cells established before vaccination, utilizes the 1-69 VH gene, binds to the stem of HA, and neutralizes both H1N1 and H5N1 viruses with few exceptions. These observations indicate that the sialic acid-binding pocket and its surrounding region are immunogenically very potent and majority of the B cells whose growth is newly induced by vaccination produce Abs that recognize these regions. However, they play a role in protection against influenza virus infection for a short period since variant viruses that have acquired resistance to these Abs become dominant. On the other hand, although the stem of HA is immunogenically not potent, the second type of B cells eventually becomes dominant. Thus, a selection system should function in forming the repertoire of long-lived memory B cells and the stability of the epitope would greatly affect the fate of the memory cells. Acquisition of the ability to produce Abs that bind to the stable epitope could be a major factor of flu resistance.

  10. Tetranectin-binding site on plasminogen kringle 4 involves the lysine-binding pocket and at least one additional amino acid residue

    DEFF Research Database (Denmark)

    Graversen, Jonas Heilskov; Sigurskjold, B W; Thøgersen, H C;

    2000-01-01

    of plasminogen kringle 4, which both were found to interact with the low molecular weight ligand with an almost identical geometry in the crystal of the complex, are not of equal functional importance in t-AMCHA binding. Mutating Asp 57 to an Asn totally eliminates binding, whereas the Asp 55 to Asn...

  11. Navigating into the binding pockets of the HER family protein kinases: discovery of novel EGFR inhibitor as antitumor agent

    Directory of Open Access Journals (Sweden)

    Liu W

    2015-07-01

    Full Text Available Wei Liu,1,* Jin-Feng Ning,2,* Qing-Wei Meng,1 Jing Hu,1 Yan-Bin Zhao,1 Chao Liu,3 Li Cai11The Fourth Department of Medical Oncology, Harbin Medical University Cancer Hospital, 2The Thoracic Surgery Department, Harbin Medical University Cancer Hospital, Harbin, People’s Republic of China; 3General Surgery Department, Mudanjiang Guanliju Central Hospital, Mishan, Heilongjiang Province, People’s Republic of China*These authors contributed equally to this workAbstract: The epidermal growth factor receptor (EGFR family has been validated as a successful antitumor drug target for decades. Known EGFR inhibitors were exposed to distinct drug resistance against the various EGFR mutants within non-small-cell lung cancer (NSCLC, particularly the T790M mutation. Although so far a number of studies have been reported on the development of third-generation EGFR inhibitors for overcoming the resistance issue, the design procedure largely depends on the intuition of medicinal chemists. Here we retrospectively make a detailed analysis of the 42 EGFR family protein crystal complexes deposited in the Protein Data Bank (PDB. Based on the analysis of inhibitor binding modes in the kinase catalytic cleft, we identified a potent EGFR inhibitor (compound A-10 against drug-resistant EGFR through fragment-based drug design. This compound showed at least 30-fold more potency against EGFR T790M than the two control molecules erlotinib and gefitinib in vitro. Moreover, it could exhibit potent HER2 inhibitory activities as well as tumor growth inhibitory activity. Molecular docking studies revealed a structural basis for the increased potency and mutant selectivity of this compound. Compound A-10 may be selected as a promising candidate in further preclinical studies. In addition, our findings could provide a powerful strategy to identify novel selective kinase inhibitors on the basis of detailed kinase–ligand interaction space in the PDB.Keywords: EGFR, kinase

  12. Design, synthesis and evaluation of novel HIV-1 NNRTIs with dual structural conformations targeting the entrance channel of the NNRTI binding pocket.

    Science.gov (United States)

    Meng, Qing; Chen, Xuwang; Kang, Dongwei; Huang, Boshi; Li, Wenxin; Zhan, Peng; Daelemans, Dirk; De Clercq, Erik; Pannecouque, Christophe; Liu, Xinyong

    2016-06-10

    On the basis of structure-based bioisosteric replacement and molecular hybridization strategy, a series of novel dual structural-conformation inhibitors targeting the "entrance channel" of HIV-1 NNRTIs binding pocket (NNIBP) were designed and synthesized. All of the new compounds were evaluated for their anti-HIV activities in MT-4 cells using the MTT method. Five compounds exhibited moderate to excellent potencies inhibiting wild-type (wt) HIV-1 replication with EC50 values ranging from 31.36 μM to 0.11 μM. Among them, compound 15b was identified as the most potent inhibitor with EC50 values of 0.11 μM and 2.18 μM against wt and K103N/Y181C double mutant HIV-1 strain (RES056), respectively. In addition, preliminary structure-activity relationships (SARs) and molecular simulation studies were discussed, which may provide valuable insights for further optimization. PMID:26994843

  13. Quantum Hall conductance and de Haas-van Alphen oscillation in a tight-binding model with electron and hole pockets for (TMTSF) 2NO3

    Science.gov (United States)

    Kishigi, Keita; Hasegawa, Yasumasa

    2016-08-01

    Quantized Hall conductance and de Haas-van Alphen (dHvA) oscillation are studied theoretically in the tight-binding model for (TMTSF) 2NO3 , in which there are small pockets of electrons and holes due to the periodic potentials of anion ordering in the a direction. The magnetic field is treated by hoppings as complex numbers due to the phase caused by the vector potential, i.e., Peierls substitution. In realistic values of parameters and the magnetic field, the energy as a function of the magnetic field (Hofstadter butterfly diagram) is obtained. It is shown that the energy levels are broadened and the gaps are closed or almost closed periodically as a function of the inverse magnetic field, which is not seen in the semiclassical theory of the magnetic breakdown. The Hall conductance is quantized with an integer obtained by the Diophantine equation when the chemical potential lies in an energy gap. When electrons or holes are doped in this system, the Hall conductance is quantized in some regions of a magnetic field but it is not quantized in other regions of a magnetic field due to the broadening of the Landau levels. The amplitude of the dHvA oscillation at zero temperature decreases as the magnetic field increases, while it is constant in the semiclassical Lifshitz Kosevich formula.

  14. SPIC: A novel similarity metric for comparing transcription factor binding site motifs based on information contents

    OpenAIRE

    Zhang, Shaoqiang; Zhou, Xiguo; Du, Chuanbin; Su, Zhengchang

    2013-01-01

    Background Discovering transcription factor binding sites (TFBS) is one of primary challenges to decipher complex gene regulatory networks encrypted in a genome. A set of short DNA sequences identified by a transcription factor (TF) is known as a motif, which can be expressed accurately in matrix form such as a position-specific scoring matrix (PSSM) and a position frequency matrix. Very frequently, we need to query a motif in a database of motifs by seeking its similar motifs, merge similar ...

  15. SPOT-Ligand: Fast and effective structure-based virtual screening by binding homology search according to ligand and receptor similarity.

    Science.gov (United States)

    Yang, Yuedong; Zhan, Jian; Zhou, Yaoqi

    2016-07-01

    Structure-based virtual screening usually involves docking of a library of chemical compounds onto the functional pocket of the target receptor so as to discover novel classes of ligands. However, the overall success rate remains low and screening a large library is computationally intensive. An alternative to this "ab initio" approach is virtual screening by binding homology search. In this approach, potential ligands are predicted based on similar interaction pairs (similarity in receptors and ligands). SPOT-Ligand is an approach that integrates ligand similarity by Tanimoto coefficient and receptor similarity by protein structure alignment program SPalign. The method was found to yield a consistent performance in DUD and DUD-E docking benchmarks even if model structures were employed. It improves over docking methods (DOCK6 and AUTODOCK Vina) and has a performance comparable to or better than other binding-homology methods (FINDsite and PoLi) with higher computational efficiency. The server is available at http://sparks-lab.org. © 2016 Wiley Periodicals, Inc. PMID:27074979

  16. Binding in working memory and frontal lobe in normal aging: is there any similarity with autism?

    OpenAIRE

    Lecouvey, Grégory; Quinette, Peggy; Kalpouzos, Grégoria; Guillery-Girard, Bérengère; Bejanin, Alexandre; Gonneaud, Julie; Abbas,Ahmed; Viader, Fausto; Eustache, Francis; Desgranges, Béatrice

    2015-01-01

    Some studies highlight similarities between Autism Spectrum Disorder (ASD) and healthy aging. Indeed, the decline in older individuals’ ability to create a unified representation of the individual features of an event is thought to arise from a disruption of binding within the episodic buffer of working memory (WM) as the same way as observed in ASD. In both cases, this deficit may result from an abnormal engagement of a frontohippocampal network. The objective of the present study is to iden...

  17. Crystal structure of silkworm Bombyx mori JHBP in complex with 2-methyl-2,4-pentanediol: plasticity of JH-binding pocket and ligand-induced conformational change of the second cavity in JHBP.

    Directory of Open Access Journals (Sweden)

    Zui Fujimoto

    Full Text Available Juvenile hormones (JHs control a diversity of crucial life events in insects. In Lepidoptera which major agricultural pests belong to, JH signaling is critically controlled by a species-specific high-affinity, low molecular weight JH-binding protein (JHBP in hemolymph, which transports JH from the site of its synthesis to target tissues. Hence, JHBP is expected to be an excellent target for the development of novel specific insect growth regulators (IGRs and insecticides. A better understanding of the structural biology of JHBP should pave the way for the structure-based drug design of such compounds. Here, we report the crystal structure of the silkworm Bombyx mori JHBP in complex with two molecules of 2-methyl-2,4-pentanediol (MPD, one molecule (MPD1 bound in the JH-binding pocket while the other (MPD2 in a second cavity. Detailed comparison with the apo-JHBP and JHBP-JH II complex structures previously reported by us led to a number of intriguing findings. First, the JH-binding pocket changes its size in a ligand-dependent manner due to flexibility of the gate α1 helix. Second, MPD1 mimics interactions of the epoxide moiety of JH previously observed in the JHBP-JH complex, and MPD can compete with JH in binding to the JH-binding pocket. We also confirmed that methoprene, which has an MPD-like structure, inhibits the complex formation between JHBP and JH while the unepoxydated JH III (methyl farnesoate does not. These findings may open the door to the development of novel IGRs targeted against JHBP. Third, binding of MPD to the second cavity of JHBP induces significant conformational changes accompanied with a cavity expansion. This finding, together with MPD2-JHBP interaction mechanism identified in the JHBP-MPD complex, should provide important guidance in the search for the natural ligand of the second cavity.

  18. Searching the protein structure database for ligand-binding site similarities using CPASS v.2

    Directory of Open Access Journals (Sweden)

    Caprez Adam

    2011-01-01

    Full Text Available Abstract Background A recent analysis of protein sequences deposited in the NCBI RefSeq database indicates that ~8.5 million protein sequences are encoded in prokaryotic and eukaryotic genomes, where ~30% are explicitly annotated as "hypothetical" or "uncharacterized" protein. Our Comparison of Protein Active-Site Structures (CPASS v.2 database and software compares the sequence and structural characteristics of experimentally determined ligand binding sites to infer a functional relationship in the absence of global sequence or structure similarity. CPASS is an important component of our Functional Annotation Screening Technology by NMR (FAST-NMR protocol and has been successfully applied to aid the annotation of a number of proteins of unknown function. Findings We report a major upgrade to our CPASS software and database that significantly improves its broad utility. CPASS v.2 is designed with a layered architecture to increase flexibility and portability that also enables job distribution over the Open Science Grid (OSG to increase speed. Similarly, the CPASS interface was enhanced to provide more user flexibility in submitting a CPASS query. CPASS v.2 now allows for both automatic and manual definition of ligand-binding sites and permits pair-wise, one versus all, one versus list, or list versus list comparisons. Solvent accessible surface area, ligand root-mean square difference, and Cβ distances have been incorporated into the CPASS similarity function to improve the quality of the results. The CPASS database has also been updated. Conclusions CPASS v.2 is more than an order of magnitude faster than the original implementation, and allows for multiple simultaneous job submissions. Similarly, the CPASS database of ligand-defined binding sites has increased in size by ~ 38%, dramatically increasing the likelihood of a positive search result. The modification to the CPASS similarity function is effective in reducing CPASS similarity scores

  19. Sequence similarity between the erythrocyte binding domain of the Plasmodium vivax Duffy binding protein and the V3 loop of HIV-1 strain MN reveals a functional heparin binding motif involved in binding to the Duffy antigen receptor for chemokines

    Directory of Open Access Journals (Sweden)

    Bolton Michael J

    2011-11-01

    Full Text Available Abstract Background The HIV surface glycoprotein gp120 (SU, gp120 and the Plasmodium vivax Duffy binding protein (PvDBP bind to chemokine receptors during infection and have a site of amino acid sequence similarity in their binding domains that often includes a heparin binding motif (HBM. Infection by either pathogen has been found to be inhibited by polyanions. Results Specific polyanions that inhibit HIV infection and bind to the V3 loop of X4 strains also inhibited DBP-mediated infection of erythrocytes and DBP binding to the Duffy Antigen Receptor for Chemokines (DARC. A peptide including the HBM of PvDBP had similar affinity for heparin as RANTES and V3 loop peptides, and could be specifically inhibited from heparin binding by the same polyanions that inhibit DBP binding to DARC. However, some V3 peptides can competitively inhibit RANTES binding to heparin, but not the PvDBP HBM peptide. Three other members of the DBP family have an HBM sequence that is necessary for erythrocyte binding, however only the protein which binds to DARC, the P. knowlesi alpha protein, is inhibited by heparin from binding to erythrocytes. Heparitinase digestion does not affect the binding of DBP to erythrocytes. Conclusion The HBMs of DBPs that bind to DARC have similar heparin binding affinities as some V3 loop peptides and chemokines, are responsible for specific sulfated polysaccharide inhibition of parasite binding and invasion of red blood cells, and are more likely to bind to negative charges on the receptor than cell surface glycosaminoglycans.

  20. Bovine lactoferrin binds oleic acid to form an anti-tumor complex similar to HAMLET.

    Science.gov (United States)

    Fang, Bing; Zhang, Ming; Tian, Mai; Jiang, Lu; Guo, Hui Yuan; Ren, Fa Zheng

    2014-04-01

    α-Lactalbumin (α-LA) can bind oleic acid (OA) to form HAMLET-like complexes, which exhibited highly selective anti-tumor activity in vitro and in vivo. Considering the structural similarity to α-LA, we conjectured that lactoferrin (LF) could also bind OA to obtain a complex with anti-tumor activity. In this study, LF-OA was prepared and its activity and structural changes were compared with α-LA-OA. The anti-tumor activity was evaluated by methylene blue assay, while the apoptosis mechanism was analyzed using flow cytometry and Western blot. Structural changes of LF-OA were measured by fluorescence spectroscopy and circular dichroism. The interactions of OA with LF and α-LA were evaluated by isothermal titration calorimetry (ITC). LF-OA was obtained by heat-treatment at pH8.0 with LD50 of 4.88, 4.95 and 4.62μM for HepG2, HT29, and MCF-7 cells, respectively, all of which were 10 times higher than those of α-LA-OA. Similar to HAMLET, LF-OA induced apoptosis in tumor cells through both death receptor- and mitochondrial-mediated pathways. Exposure of tryptophan residues and the hydrophobic regions as well as the loss of tertiary structure were observed in LF-OA. Besides these similarities, LF showed different secondary structure changes when compared with α-LA, with a decrease of α-helix and β-turn and an increase of β-sheet and random coil. ITC results showed that there was a higher binding number of OA to LF than to α-LA, while both of the proteins interacted with OA through van der Waals forces and hydrogen bonds. This study provides a theoretical basis for further exploration of protein-OA complexes. PMID:24368211

  1. Nonlinear scoring functions for similarity-based ligand docking and binding affinity prediction.

    Science.gov (United States)

    Brylinski, Michal

    2013-11-25

    A common strategy for virtual screening considers a systematic docking of a large library of organic compounds into the target sites in protein receptors with promising leads selected based on favorable intermolecular interactions. Despite a continuous progress in the modeling of protein-ligand interactions for pharmaceutical design, important challenges still remain, thus the development of novel techniques is required. In this communication, we describe eSimDock, a new approach to ligand docking and binding affinity prediction. eSimDock employs nonlinear machine learning-based scoring functions to improve the accuracy of ligand ranking and similarity-based binding pose prediction, and to increase the tolerance to structural imperfections in the target structures. In large-scale benchmarking using the Astex/CCDC data set, we show that 53.9% (67.9%) of the predicted ligand poses have RMSD of <2 Å (<3 Å). Moreover, using binding sites predicted by recently developed eFindSite, eSimDock models ligand binding poses with an RMSD of 4 Å for 50.0-39.7% of the complexes at the protein homology level limited to 80-40%. Simulations against non-native receptor structures, whose mean backbone rearrangements vary from 0.5 to 5.0 Å Cα-RMSD, show that the ratio of docking accuracy and the estimated upper bound is at a constant level of ∼0.65. Pearson correlation coefficient between experimental and predicted by eSimDock Ki values for a large data set of the crystal structures of protein-ligand complexes from BindingDB is 0.58, which decreases only to 0.46 when target structures distorted to 3.0 Å Cα-RMSD are used. Finally, two case studies demonstrate that eSimDock can be customized to specific applications as well. These encouraging results show that the performance of eSimDock is largely unaffected by the deformations of ligand binding regions, thus it represents a practical strategy for across-proteome virtual screening using protein models. eSimDock is freely

  2. Acetylcholine-Binding Protein Engineered to Mimic the α4-α4 Binding Pocket in α4β2 Nicotinic Acetylcholine Receptors Reveals Interface Specific Interactions Important for Binding and Activity

    DEFF Research Database (Denmark)

    Shahsavar, Azadeh; Ahring, Philip K; Olsen, Jeppe A;

    2015-01-01

    residues, H142, Q150, and T152, were demonstrated to be involved in the distinct pharmacology of the α4-α4 versus α4-β2 binding sites. To obtain insight into the three-dimensional structure of the α4-α4 binding site, a surrogate protein reproducing α4-α4 binding characteristics was constructed by...

  3. Reinventing Pocket Microscopy

    CERN Document Server

    Kamal, T; Lee, W M

    2015-01-01

    The key to the success of pocket microscopes stems from the convenience for anyone to magnify the fine details (tens of micrometres) of any object on-thespot. The capability with a portable microscope lets us surpass our limited vision and is commonly used in many areas of science, industry, education. The growth of imaging and computing power in smartphones is creating the possibility of converting your smartphone into a high power pocket microscope. In this article, we briefly describe the history of pocket microscopy and elucidate how mobile technologies are set to become the next platform for pocket microscopes

  4. Pocket pumped image analysis

    Energy Technology Data Exchange (ETDEWEB)

    Kotov, I.V., E-mail: kotov@bnl.gov [Brookhaven National Laboratory, Upton, NY 11973 (United States); O' Connor, P. [Brookhaven National Laboratory, Upton, NY 11973 (United States); Murray, N. [Centre for Electronic Imaging, Open University, Milton Keynes, MK7 6AA (United Kingdom)

    2015-07-01

    The pocket pumping technique is used to detect small electron trap sites. These traps, if present, degrade CCD charge transfer efficiency. To reveal traps in the active area, a CCD is illuminated with a flat field and, before image is read out, accumulated charges are moved back and forth number of times in parallel direction. As charges are moved over a trap, an electron is removed from the original pocket and re-emitted in the following pocket. As process repeats one pocket gets depleted and the neighboring pocket gets excess of charges. As a result a “dipole” signal appears on the otherwise flat background level. The amplitude of the dipole signal depends on the trap pumping efficiency. This paper is focused on trap identification technique and particularly on new methods developed for this purpose. The sensor with bad segments was deliberately chosen for algorithms development and to demonstrate sensitivity and power of new methods in uncovering sensor defects.

  5. How Similar Are Protein Folding and Protein Binding Nuclei? Examination of Vibrational Motions of Energy Hot Spots and Conserved Residues

    OpenAIRE

    Haliloglu, Turkan; Keskin, Ozlem; Ma, Buyong; Nussinov, Ruth

    2004-01-01

    The underlying physico-chemical principles of the interactions between domains in protein folding are similar to those between protein molecules in binding. Here we show that conserved residues and experimental hot spots at intermolecular binding interfaces overlap residues that vibrate with high frequencies. Similarly, conserved residues and hot spots are found in protein cores and are also observed to vibrate with high frequencies. In both cases, these residues contribute significantly to t...

  6. Structure of the HIV-1 reverse transcriptase Q151M mutant: insights into the inhibitor resistance of HIV-1 reverse transcriptase and the structure of the nucleotide-binding pocket of Hepatitis B virus polymerase.

    Science.gov (United States)

    Nakamura, Akiyoshi; Tamura, Noriko; Yasutake, Yoshiaki

    2015-11-01

    Hepatitis B virus polymerase (HBV Pol) is an important target for anti-HBV drug development; however, its low solubility and stability in vitro has hindered detailed structural studies. Certain nucleotide reverse transcriptase (RT) inhibitors (NRTIs) such as tenofovir and lamivudine can inhibit both HBV Pol and Human immunodeficiency virus 1 (HIV-1) RT, leading to speculation on structural and mechanistic analogies between the deoxynucleotide triphosphate (dNTP)-binding sites of these enzymes. The Q151M mutation in HIV-1 RT, located at the dNTP-binding site, confers resistance to various NRTIs, while maintaining sensitivity to tenofovir and lamivudine. The residue corresponding to Gln151 is strictly conserved as a methionine in HBV Pol. Therefore, the structure of the dNTP-binding pocket of the HIV-1 RT Q151M mutant may reflect that of HBV Pol. Here, the crystal structure of HIV-1 RT Q151M, determined at 2.6 Å resolution, in a new crystal form with space group P321 is presented. Although the structure of HIV-1 RT Q151M superimposes well onto that of HIV-1 RT in a closed conformation, a slight movement of the β-strands (β2-β3) that partially create the dNTP-binding pocket was observed. This movement might be caused by the introduction of the bulky thioether group of Met151. The structure also highlighted the possibility that the hydrogen-bonding network among amino acids and NRTIs is rearranged by the Q151M mutation, leading to a difference in the affinity of NRTIs for HIV-1 RT and HBV Pol. PMID:26527265

  7. Structure of the HIV-1 reverse transcriptase Q151M mutant: insights into the inhibitor resistance of HIV-1 reverse transcriptase and the structure of the nucleotide-binding pocket of Hepatitis B virus polymerase

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, Akiyoshi; Tamura, Noriko; Yasutake, Yoshiaki, E-mail: y-yasutake@aist.go.jp [National Institute of Advanced Industrial Science and Technology (AIST), 2-17-2-1 Tsukisamu-Higashi, Toyohira, Sapporo, Hokkaido 062-8517 (Japan)

    2015-10-23

    The structure of the HIV-1 reverse transcriptase Q151M mutant was determined at a resolution of 2.6 Å in space group P321. Hepatitis B virus polymerase (HBV Pol) is an important target for anti-HBV drug development; however, its low solubility and stability in vitro has hindered detailed structural studies. Certain nucleotide reverse transcriptase (RT) inhibitors (NRTIs) such as tenofovir and lamivudine can inhibit both HBV Pol and Human immunodeficiency virus 1 (HIV-1) RT, leading to speculation on structural and mechanistic analogies between the deoxynucleotide triphosphate (dNTP)-binding sites of these enzymes. The Q151M mutation in HIV-1 RT, located at the dNTP-binding site, confers resistance to various NRTIs, while maintaining sensitivity to tenofovir and lamivudine. The residue corresponding to Gln151 is strictly conserved as a methionine in HBV Pol. Therefore, the structure of the dNTP-binding pocket of the HIV-1 RT Q151M mutant may reflect that of HBV Pol. Here, the crystal structure of HIV-1 RT Q151M, determined at 2.6 Å resolution, in a new crystal form with space group P321 is presented. Although the structure of HIV-1 RT Q151M superimposes well onto that of HIV-1 RT in a closed conformation, a slight movement of the β-strands (β2–β3) that partially create the dNTP-binding pocket was observed. This movement might be caused by the introduction of the bulky thioether group of Met151. The structure also highlighted the possibility that the hydrogen-bonding network among amino acids and NRTIs is rearranged by the Q151M mutation, leading to a difference in the affinity of NRTIs for HIV-1 RT and HBV Pol.

  8. Binding in working memory and frontal lobe in normal aging: is there any similarity with autism?

    Directory of Open Access Journals (Sweden)

    Gregory eLecouvey

    2015-03-01

    Full Text Available Some studies highlight similarities between Autism Spectrum Disorder (ASD and healthy aging. Indeed, the decline in older individuals’ ability to create a unified representation of the individual features of an event is thought to arise from a disruption of integration within the episodic buffer of working memory as the same way as observed in ASD. In both cases, this deficit may result from an abnormal engagement of a frontohippocampal network. The objective of the present study is to identify both cognitive processes and neural substrates associated to the deficit of integration in healthy aging. We studied the capacity of integration and the cognitive processes that might mediate its decline in 72 healthy participants aged 18-84 years. We confronted the behavioral data to the changes in brain metabolism associated with the age-related decline in a subgroup of 34 healthy participants aged 20-77 years using the resting-state [18F] fluorodeoxyglucose positron emission tomography (18F-FDG PET. Forward stepwise regression analyses showed that the age-related decline in binding was partially explained by a decline in inhibition and processing speed. PET correlation analyses indicated that metabolism of the medial frontal regions, anterior and middle cingulate cortices is implicated in this phenomenon. These data suggest that executive functions and processing speed may play a crucial rule in the capacity to integrate unified representations in memory in aging. Possible implications are discussed in ASD.

  9. f POP: footprinting functional pockets of proteins by comparative spatial patterns

    OpenAIRE

    Tseng, Yan Yuan; Chen, Z. Jeffrey; Li, Wen-Hsiung

    2009-01-01

    f POP (footprinting Pockets Of Proteins, http://pocket.uchicago.edu/fpop/) is a relational database of the protein functional surfaces identified by analyzing the shapes of binding sites in ∼42 700 structures, including both holo and apo forms. We previously used a purely geometric method to extract the spatial patterns of functional surfaces (split pockets) in ∼19 000 bound structures and constructed a database, SplitPocket (http://pocket.uchicago.edu/). These functional surfaces are now use...

  10. Derivation of an amino acid similarity matrix for peptide:MHC binding and its application as a Bayesian prior

    Directory of Open Access Journals (Sweden)

    Sette Alessandro

    2009-11-01

    Full Text Available Abstract Background Experts in peptide:MHC binding studies are often able to estimate the impact of a single residue substitution based on a heuristic understanding of amino acid similarity in an experimental context. Our aim is to quantify this measure of similarity to improve peptide:MHC binding prediction methods. This should help compensate for holes and bias in the sequence space coverage of existing peptide binding datasets. Results Here, a novel amino acid similarity matrix (PMBEC is directly derived from the binding affinity data of combinatorial peptide mixtures. Like BLOSUM62, this matrix captures well-known physicochemical properties of amino acid residues. However, PMBEC differs markedly from existing matrices in cases where residue substitution involves a reversal of electrostatic charge. To demonstrate its usefulness, we have developed a new peptide:MHC class I binding prediction method, using the matrix as a Bayesian prior. We show that the new method can compensate for missing information on specific residues in the training data. We also carried out a large-scale benchmark, and its results indicate that prediction performance of the new method is comparable to that of the best neural network based approaches for peptide:MHC class I binding. Conclusion A novel amino acid similarity matrix has been derived for peptide:MHC binding interactions. One prominent feature of the matrix is that it disfavors substitution of residues with opposite charges. Given that the matrix was derived from experimentally determined peptide:MHC binding affinity measurements, this feature is likely shared by all peptide:protein interactions. In addition, we have demonstrated the usefulness of the matrix as a Bayesian prior in an improved scoring-matrix based peptide:MHC class I prediction method. A software implementation of the method is available at: http://www.mhc-pathway.net/smmpmbec.

  11. Trends for isolated amino acids and dipeptides: Conformation, divalent ion binding, and remarkable similarity of binding to calcium and lead

    CERN Document Server

    Ropo, Matti; Baldauf, Carsten

    2016-01-01

    We derive structural and binding energy trends for twenty amino acids, their dipeptides, and their interactions with the divalent cations Ca$^{2+}$, Ba$^{2+}$, Sr$^{2+}$, Cd$^{2+}$, Pb$^{2+}$, and Hg$^{2+}$. The underlying data set consists of 45,892 first-principles predicted conformers with relative energies up to about 4 eV (about 400kJ/mol). We show that only very few distinct backbone structures of isolated amino acids and their dipeptides emerge as lowest-energy conformers. The isolated amino acids predominantly adopt structures that involve an acidic proton shared between the carboxy and amino function. Dipeptides adopt one of two intramolecular-hydrogen bonded conformations C$_5$ or equatorial C$_7$. Upon complexation with a divalent cation, the accessible conformational space shrinks and intramolecular hydrogen bonding is prevented due to strong electrostatic interaction of backbone and side chain functional groups with cations. Clear correlations emerge from the binding energies of the six divalent ...

  12. Protein PocketViewer: A Web-Service Based Interface for Protein Pocket Extraction and Visualization

    Directory of Open Access Journals (Sweden)

    Xiaoyu Zhang

    2013-09-01

    Full Text Available One important problem in bioinformatics is to study pockets or tunnels within the protein structure. These pocket or tunnel regions are significant because they indicate areas of ligand binding or enzymatic reactions, and tunnels are often solvent ion conductance areas. The Protein Pocket Viewer (PPV is a web interface that allows the user to extract and visualize the protein pockets in a browser, based on the algorithm in [1]. The PPV packaged the pocket extraction executable as a web service, and made it accessible to all users with the Internet access and a modern java enabled browser. The PPV employed the Model2design pattern, which led to a loosely coupled implementation that is more robust and easier to maintain. It consists of a client web interface for user inputs and visualization, a middle-layer for controlling the flow, and the backend web services performing the actual CPU-intensive computation. The PPV web client consists of multiple window regions, with each region providing differing views of the protein, pockets and related information. For a more responsive user experience, the PPV web client employs AJAX for asynchronous execution of long running tasks, like protein pocket extraction.

  13. Newnes electrical pocket book

    CERN Document Server

    Reeves, E A

    2013-01-01

    Newnes Electrical Pocket Book, Twenty-first Edition, provides engineers with convenient access to various facts, tables, and formulae relating to the particular branch of engineering being dealt with. In the case of electrical engineering, it is essential that the engineer have a clear understanding of the methods by which the various formulae are derived to ensure that any particular formulae is applicable to the conditions being considered. The first section of the Pocket Book is devoted to the theoretical groundwork upon which all the practical applications are based. This covers symbols,

  14. Google Pocket Guide

    CERN Document Server

    Calishain, Tara; Adams, DJ

    2003-01-01

    Beneath its deceptively simple search form, Google is a remarkably powerful and flexible search engine that indexes billions of web pages, handling more than 150 million searches a day. You know that what you're looking for must be in there somewhere, but how do you make Google work for you? Crafted from our best-selling Google Hacks title, the Google Pocket Guide provides exactly the information you need to make your searches faster and more effective, right from the start. The Google Pocket Guide unleashes the power behind that blinking cursor by delivering: A thorough but concise tour o

  15. VBScript pocket reference

    CERN Document Server

    Lomax, Paul; Petrusha, Ron

    2008-01-01

    Microsoft's Visual Basic Scripting Edition (VBScript), a subset of Visual Basic for Applications, is a powerful language for Internet application development, where it can serve as a scripting language for server-side, client-side, and system scripting. Whether you're developing code for Active Server Pages, client-side scripts for Internet Explorer, code for Outlook forms, or scripts for Windows Script Host, VBScript Pocket Reference will be your constant companion. Don't let the pocket-friendly format fool you. Based on the bestsellingVBScript in a Nutshell, this small book details every V

  16. HTML & XHTML Pocket Reference

    CERN Document Server

    Robbins, Jennifer

    2010-01-01

    After years of using spacer GIFs, layers of nested tables, and other improvised solutions for building your web sites, getting used to the more stringent standards-compliant design can be intimidating. HTML and XHTML Pocket Reference is the perfect little book when you need answers immediately. Jennifer Niederst-Robbins, author Web Design in a Nutshell, has revised and updated the fourth edition of this pocket guide by taking the top 20% of vital reference information from her Nutshell book, augmenting it judiciously, cross-referencing everything, and organizing it according to the most com

  17. The CK2 alpha/CK2 beta interface of human protein kinase CK2 harbors a binding pocket for small molecules

    DEFF Research Database (Denmark)

    Raaf, Jennifer; Brunstein, Elena; Issinger, Olaf-Georg; Niefind, Karsten

    2008-01-01

    The Ser/Thr kinase CK2 (previously called casein kinase 2) is composed of two catalytic chains (CK2 alpha) attached to a dimer of noncatalytic subunits (CK2 beta). CK2 is involved in suppression of apoptosis, cell survival, and tumorigenesis. To investigate these activities and possibly affect them......, selective CK2 inhibitors are required. An often-used CK2 inhibitor is 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB). In a complex structure with human CK2 alpha, DRB binds to the canonical ATP cleft, but additionally it occupies an allosteric site that can be alternatively filled by glycerol....... Inhibition kinetic studies corroborate the dual binding mode of the inhibitor. Structural comparisons reveal a surprising conformational plasticity of human CK2 alpha around both DRB binding sites. After local rearrangement, the allosteric site serves as a CK2 beta interface. This opens the potential to...

  18. Similar serotonin-2A receptor binding in rats with different coping styles or levels of aggression

    DEFF Research Database (Denmark)

    Visser, Anniek Kd; Ettrup, Anders; Klein, Anders Bue;

    2015-01-01

    important molecular marker for coping style. Since neither an antagonist nor an agonist tracer showed any binding differences, it is unlikely that the affinity state of the 5-HT2A R is co-varying with levels of aggression or active avoidance in WTG, RHA and RLA. This article is protected by copyright. All...

  19. Data communications pocket book

    CERN Document Server

    Tooley, Michael

    2014-01-01

    Data Communications Pocket Book, Second Edition presents information relevant to data communication. The book provides tabulated reference materials with a brief description and diagrams. The coverage of the text includes abbreviations, terminal control codes, and conversion tables. The text will be of great use to individuals involved in the interconnection of computer systems.

  20. Structure of an Odorant-Vinding Protein form the Mosquito Aedes aegypti Suggests a Binding Pocket Covered by a pH-Sensitive

    Energy Technology Data Exchange (ETDEWEB)

    N Leite; R Krogh; W Xu; Y Ishida; J Iulek; W Leal; G Oliva

    2011-12-31

    The yellow fever mosquito, Aedes aegypti, is the primary vector for the viruses that cause yellow fever, mostly in tropical regions of Africa and in parts of South America, and human dengue, which infects 100 million people yearly in the tropics and subtropics. A better understanding of the structural biology of olfactory proteins may pave the way for the development of environmentally-friendly mosquito attractants and repellents, which may ultimately contribute to reduction of mosquito biting and disease transmission. Previously, we isolated and cloned a major, female-enriched odorant-binding protein (OBP) from the yellow fever mosquito, AaegOBP1, which was later inadvertently renamed AaegOBP39. We prepared recombinant samples of AaegOBP1 by using an expression system that allows proper formation of disulfide bridges and generates functional OBPs, which are indistinguishable from native OBPs. We crystallized AaegOBP1 and determined its three-dimensional structure at 1.85 {angstrom} resolution by molecular replacement based on the structure of the malaria mosquito OBP, AgamOBP1, the only mosquito OBP structure known to date. The structure of AaegOBP1 (= AaegOBP39) shares the common fold of insect OBPs with six {alpha}-helices knitted by three disulfide bonds. A long molecule of polyethylene glycol (PEG) was built into the electron-density maps identified in a long tunnel formed by a crystallographic dimer of AaegOBP1. Circular dichroism analysis indicated that delipidated AaegOBP1 undergoes a pH-dependent conformational change, which may lead to release of odorant at low pH (as in the environment in the vicinity of odorant receptors). A C-terminal loop covers the binding cavity and this 'lid' may be opened by disruption of an array of acid-labile hydrogen bonds thus explaining reduced or no binding affinity at low pH.

  1. Functions of key residues in the ligand-binding pocket of vitamin D receptor: Fragment molecular orbital interfragment interaction energy analysis

    Science.gov (United States)

    Yamagishi, Kenji; Yamamoto, Keiko; Yamada, Sachiko; Tokiwa, Hiroaki

    2006-03-01

    Fragment molecular orbital-interfragment interaction energy calculations of the vitamin D receptor (VDR)/1α,25-dihydroxyvitamin D 3 complex were utilized to assign functions of key residues of the VDR. Only one residue forms a significant interaction with the corresponding hydroxy group of the ligand, although two residues are located around each hydroxy group. The degradation of binding affinity for derivatives upon removal of a hydroxy group is closely related to the trend in the strength of the hydrogen bonds. Type II hereditary rickets due to an Arg274 point mutation is caused by the lack of the strongest hydrogen bond.

  2. Interaction pattern of Arg 62 in the A-pocket of differentially disease-associated HLA-B27 subtypes suggests distinct TCR binding modes.

    Directory of Open Access Journals (Sweden)

    Elisa Nurzia

    Full Text Available The single amino acid replacement Asp116His distinguishes the two subtypes HLA-B*2705 and HLA-B*2709 which are, respectively, associated and non-associated with Ankylosing Spondylitis, an autoimmune chronic inflammatory disease. The reason for this differential association is so far poorly understood and might be related to subtype-specific HLA:peptide conformations as well as to subtype/peptide-dependent dynamical properties on the nanoscale. Here, we combine functional experiments with extensive molecular dynamics simulations to investigate the molecular dynamics and function of the conserved Arg62 of the α1-helix for both B27 subtypes in complex with the self-peptides pVIPR (RRKWRRWHL and TIS (RRLPIFSRL, and the viral peptides pLMP2 (RRRWRRLTV and NPflu (SRYWAIRTR. Simulations of HLA:peptide systems suggest that peptide-stabilizing interactions of the Arg62 residue observed in crystal structures are metastable for both B27 subtypes under physiological conditions, rendering this arginine solvent-exposed and, probably, a key residue for TCR interaction more than peptide-binding. This view is supported by functional experiments with conservative (R62K and non-conservative (R62A B*2705 and B*2709 mutants that showed an overall reduction in their capability to present peptides to CD8+ T cells. Moreover, major subtype-dependent differences in the peptide recognition suggest distinct TCR binding modes for the B*2705 versus the B*2709 subtype.

  3. SQL Pocket Guide

    CERN Document Server

    Gennick, Jonathan

    2010-01-01

    If you're a programmer or database administrator who uses SQL in your day-to-day work, this popular pocket guide is the ideal on-the-job reference. You'll find many examples that address the language's complexity, along with key aspects of SQL used in IBM DB2 Release 9.7, MySQL 5.1, Oracle Database 11g Release 2, PostgreSQL 9.0, and Microsoft SQL Server 2008 Release 2. SQL Pocket Guide describes how these database systems implement SQL syntax for querying, managing transactions, and making changes to data. It also shows how the systems use SQL functions, regular expression syntax, and type c

  4. Software engineer's pocket book

    CERN Document Server

    Tooley, Michael

    2013-01-01

    Software Engineer's Pocket Book provides a concise discussion on various aspects of software engineering. The book is comprised of six chapters that tackle various areas of concerns in software engineering. Chapter 1 discusses software development, and Chapter 2 covers programming languages. Chapter 3 deals with operating systems. The book also tackles discrete mathematics and numerical computation. Data structures and algorithms are also explained. The text will be of great use to individuals involved in the specification, design, development, implementation, testing, maintenance, and qualit

  5. A tight-binding model of CO chemisorption on Pd/Ta(110) and similar systems

    International Nuclear Information System (INIS)

    Chemisorption of an isolated CO molecule at various adsorption sites above the epitaxial Pd overlayer on Ta(110), and on related systems, is studied by using a self-consistent tight-binding scheme. Basic assumptions of the model are discussed in detail. The σ donation and especially the π backdonation are generally a good deal reduced at the bimetallic surface as compared with the pure Pd(111) surface. Simultaneously, the bond between CO and the surface becomes weaker. However, for CO in the atop position the effect is considerably smaller than for sites with twofold or threefold coordination and the atop site can therefore become preferred. A simple bonding picture explaining the gross trends is suggested. Core-level shifts induced in surface atoms by the adsorption are briefly discussed. (authors)

  6. Binding in working memory and frontal lobe in normal aging: is there any similarity with autism?

    OpenAIRE

    Grégoria Kalpouzos; Berengere Guillery-Girard

    2015-01-01

    Some studies highlight similarities between Autism Spectrum Disorder (ASD) and healthy aging. Indeed, the decline in older individuals’ ability to create a unified representation of the individual features of an event is thought to arise from a disruption of integration within the episodic buffer of working memory as the same way as observed in ASD. In both cases, this deficit may result from an abnormal engagement of a frontohippocampal network. The objective of the present study is to ident...

  7. Hematopoietic cytokines: similarities and differences in the structures, with implications for receptor binding.

    OpenAIRE

    Wlodawer, A; A. Pavlovsky; Gustchina, A.

    1993-01-01

    Crystal and NMR structures of helical cytokines--interleukin-4 (IL-4), granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukin-2 (IL-2)--have been compared. Root mean square deviations in the C alpha coordinates for the conserved regions of the helices were 1-2 A between different cytokines, about twice the differences observed for independently determined crystal and solution structures of IL-4. Considerable similarity in amino acid sequence in the areas expected to intera...

  8. Regular Expression Pocket Reference

    CERN Document Server

    Stubblebine, Tony

    2007-01-01

    This handy little book offers programmers a complete overview of the syntax and semantics of regular expressions that are at the heart of every text-processing application. Ideal as a quick reference, Regular Expression Pocket Reference covers the regular expression APIs for Perl 5.8, Ruby (including some upcoming 1.9 features), Java, PHP, .NET and C#, Python, vi, JavaScript, and the PCRE regular expression libraries. This concise and easy-to-use reference puts a very powerful tool for manipulating text and data right at your fingertips. Composed of a mixture of symbols and text, regular exp

  9. Pocket ECG electrode

    Science.gov (United States)

    Lund, Gordon F. (Inventor)

    1982-01-01

    A low-noise electrode suited for sensing electrocardiograms when chronically and subcutaneously implanted in a free-ranging subject. The electrode comprises a pocket-shaped electrically conductive member with a single entrance adapted to receive body fluids. The exterior of the member and the entrance region is coated with electrical insulation so that the only electrolyte/electrode interface is within the member remote from artifact-generating tissue. Cloth straps are bonded to the member to permit the electrode to be sutured to tissue and to provide electrical lead flexure relief.

  10. JDBC Pocket Reference

    CERN Document Server

    Bales, Donald

    2003-01-01

    JDBC--the Java Database Connectivity specification--is a complex set of application programming interfaces (APIs) that developers need to understand if they want their Java applications to work with databases. JDBC is so complex that even the most experienced developers need to refresh their memories from time to time on specific methods and details. But, practically speaking, who wants to stop and thumb through a weighty tutorial volume each time a question arises? The answer is the JDBC Pocket Reference, a data-packed quick reference that is both a time-saver and a lifesaver. The JDBC P

  11. XSLT 10 Pocket Reference

    CERN Document Server

    Lenz, Evan

    2008-01-01

    XSLT is an essential tool for converting XML into other kinds of documents: HTML, PDF file, and many others. It's a critical technology for XML-based platforms such as Microsoft .NET, Sun Microsystems' Sun One, as well as for most web browsers and authoring tools. As useful as XSLT is, however, most people have a difficult time getting used to its peculiar characteristics. The ability to use advanced techniques depends on a clear and exact understanding of how XSLT templates work and interact. The XSLT 1.0 Pocket Reference from O'Reilly wants to make sure you achieve that level of understan

  12. Perl Debugger Pocket Reference

    CERN Document Server

    Foley, Richard

    2004-01-01

    Most Perl programmers know about the Perl debugger--the nifty little built-in utility that you can use to fully debug any programs that you write. Inside the interactive debugger environment, you're prompted for commands that let you examine your source code, set breakpoints, dump out function call stacks, change values of variables, and much more. It's so convenient that some programmers run it just to test out Perl constructs as they create a program. But although it's on their radar, not many Perl programmers take the time to master the debugger. That's where the Perl Debugger Pocket Refer

  13. Python pocket reference

    CERN Document Server

    Lutz, Mark

    2010-01-01

    This is the book to reach for when you're coding on the fly and need an answer now. It's an easy-to-use reference to the core language, with descriptions of commonly used modules and toolkits, and a guide to recent changes, new features, and upgraded built-ins -- all updated to cover Python 3.X as well as version 2.6. You'll also quickly find exactly what you need with the handy index. Written by Mark Lutz -- widely recognized as the world's leading Python trainer -- Python Pocket Reference, Fourth Edition, is the perfect companion to O'Reilly's classic Python tutorials, also written by Mark

  14. CSS Pocket Reference

    CERN Document Server

    Meyer, Eric A

    2007-01-01

    They say that good things come in small packages, and it's certainly true for this edition of CSS Pocket Reference. Completely revised and updated to reflect the latest Cascading Style Sheet specifications in CSS 2.1, this indispensable little book covers the most essential information that web designers and developers need to implement CSS effectively across all browsers. Inside, you'll find: A short introduction to the key concepts of CSS A complete alphabetical reference to all CSS 2.1 selectors and properties A chart displaying detailed information about CSS support for every style ele

  15. Electronics pocket book

    CERN Document Server

    Parr, E A

    1981-01-01

    Electronics Pocket Book, Fourth Edition is a nonmathematical presentation of the many varied topics covered by electronics. The book tackles electron physics, electronic components (i.e. resistors, capacitors, and conductors), integrated circuits, and the principles of a.c. and d.c. amplifiers. The text also discusses oscillators, digital circuits, digital computers, and optoelectronics (i.e., sensors, emitters, and devices that utilize light). Communications (such as line and radio communications, transmitters, receivers, and digital techniques); the principles and examples of servosystems; a

  16. RTF Pocket Guide

    CERN Document Server

    Burke, Sean

    2008-01-01

    Rich Text Format, or RTF, is the internal markup language used by Microsoft Word and understood by dozens of other word processors. RTF is a universal file format that pervades practically every desktop. Because RTF is text, it's much easier to generate and process than binary .doc files. Any programmer working with word processing documents needs to learn enough RTF to get around, whether it's to format text for Word (or almost any other word processor), to make global changes to an existing document, or to convert Word files to (or from) another format. RTF Pocket Guide is a concise and e

  17. STL pocket reference

    CERN Document Server

    Lischner, Ray

    2003-01-01

    The STL Pocket Reference describes the functions, classes, and templates in that part of the C++ standard library often referred to as the Standard Template Library (STL). The STL encompasses containers, iterators, algorithms, and function objects, which collectively represent one of the most important and widely used subsets of standard library functionality. The C++ standard library, even the subset known as the STL, is vast. It's next to impossible to work with the STL without some sort of reference at your side to remind you of template parameters, function invocations, return types--ind

  18. Linux Desktop Pocket Guide

    CERN Document Server

    Brickner, David

    2005-01-01

    While Mac OS X garners all the praise from pundits, and Windows XP attracts all the viruses, Linux is quietly being installed on millions of desktops every year. For programmers and system administrators, business users, and educators, desktop Linux is a breath of fresh air and a needed alternative to other operating systems. The Linux Desktop Pocket Guide is your introduction to using Linux on five of the most popular distributions: Fedora, Gentoo, Mandriva, SUSE, and Ubuntu. Despite what you may have heard, using Linux is not all that hard. Firefox and Konqueror can handle all your web bro

  19. CSS Pocket Reference

    CERN Document Server

    Meyer, Eric

    2011-01-01

    When you're working with CSS and need a quick answer, CSS Pocket Reference delivers. This handy, concise book provides all of the essential information you need to implement CSS on the fly. Ideal for intermediate to advanced web designers and developers, the 4th edition is revised and updated for CSS3, the latest version of the Cascading Style Sheet specification. Along with a complete alphabetical reference to CSS3 selectors and properties, you'll also find a short introduction to the key concepts of CSS. Based on Cascading Style Sheets: The Definitive Guide, this reference is an easy-to-us

  20. Rails Pocket Reference

    CERN Document Server

    Berry, Eric

    2008-01-01

    Rails 2.1 brings a new level of stability and power to this acclaimed web development framework, but keeping track of its numerous moving parts is still a chore. Rails Pocket Reference offers you a painless alternative to hunting for resources online, with brief yet thorough explanations of the most frequently used methods and structures supported by Rails 2.1, along with key concepts you need to work through the framework's most tangled corners. Organized to help you quickly find what you need, this book will not only get you up to speed on how Rails works, it also provides a handy referenc

  1. Newnes microprocessor pocket book

    CERN Document Server

    Money, Steve

    2014-01-01

    Newnes Microprocessor Pocket Book explains the basic hardware operation of a microprocessor and describes the actions of the various types of instruction that can be executed. A summary of the characteristics of many of the popular microprocessors is presented. Apart from the popular 8- and 16-bit microprocessors, some details are also given of the popular single chip microcomputers and of the reduced instruction set computer (RISC) type processors such as the Transputer, Novix FORTH processor, and Acorn ARM processor.Comprised of 15 chapters, this book discusses the principles involved in bot

  2. Perl Pocket Reference

    CERN Document Server

    Vromans, Johan

    2011-01-01

    If you have a Perl programming question, you'll find the answer quickly in this handy, easy-to-use quick reference. The Perl Pocket Reference condenses and organizes stacks of documentation down to the most essential facts, so you can find what you need in a heartbeat. Updated for Perl 5.14, the 5th edition provides a summary of Perl syntax rules and a complete list of operators, built-in functions, and other features. It's the perfect companion to O'Reilly's authoritative and in-depth Perl programming books, including Learning Perl, Programming Perl, and the Perl Cookbook..

  3. Word Pocket Guide

    CERN Document Server

    Glenn, Walter

    2004-01-01

    Millions of people use Microsoft Word every day and, chances are, you're one of them. Like most Word users, you've attained a certain level of proficiency--enough to get by, with a few extra tricks and tips--but don't get the opportunity to probe much further into the real power of Word. And Word is so rich in features that regardless of your level of expertise, there's always more to master. If you've ever wanted a quick answer to a nagging question or had the thought that there must be a better way, then this second edition of Word Pocket Guide is just what you need. Updated for Word 2003

  4. Hydrophobic pocket targeting probes for enteroviruses

    Science.gov (United States)

    Martikainen, Mari; Salorinne, Kirsi; Lahtinen, Tanja; Malola, Sami; Permi, Perttu; Häkkinen, Hannu; Marjomäki, Varpu

    2015-10-01

    Visualization and tracking of viruses without compromising their functionality is crucial in order to understand virus targeting to cells and tissues, and to understand the subsequent subcellular steps leading to virus uncoating and replication. Enteroviruses are important human pathogens causing a vast number of acute infections, and are also suggested to contribute to the development of chronic diseases like type I diabetes. Here, we demonstrate a novel method to target site-specifically the hydrophobic pocket of enteroviruses. A probe, a derivative of Pleconaril, was developed and conjugated to various labels that enabled the visualization of enteroviruses under light and electron microscopes. The probe mildly stabilized the virus particle by increasing the melting temperature by 1-3 degrees, and caused a delay in the uncoating of the virus in the cellular endosomes, but could not however inhibit the receptor binding, cellular entry or infectivity of the virus. The hydrophobic pocket binding moiety of the probe was shown to bind to echovirus 1 particle by STD and tr-NOESY NMR methods. Furthermore, binding to echovirus 1 and Coxsackievirus A9, and to a lesser extent to Coxsackie virus B3 was verified by using a gold nanocluster labeled probe by TEM analysis. Molecular modelling suggested that the probe fits the hydrophobic pockets of EV1 and CVA9, but not of CVB3 as expected, correlating well with the variations in the infectivity and stability of the virus particles. EV1 conjugated to the fluorescent dye labeled probe was efficiently internalized into the cells. The virus-fluorescent probe conjugate accumulated in the cytoplasmic endosomes and caused infection starting from 6 hours onwards. Remarkably, before and during the time of replication, the fluorescent probe was seen to leak from the virus-positive endosomes and thus separate from the capsid proteins that were left in the endosomes. These results suggest that, like the physiological hydrophobic content

  5. BS25999 a pocket guide

    CERN Document Server

    Drewitt, Tony

    2008-01-01

    This new pocket guide provides an easy to read and straightforward introduction to the subjects of business continuity and BS 25999. If your organisation is implementing, or considering implementing, a BS 25999 business continuity management system (BCMS) then you need to read a copy of this pocket guide.

  6. Heparan sulfate chains from glypican and syndecans bind the Hep II domain of fibronectin similarly despite minor structural differences

    DEFF Research Database (Denmark)

    Tumova, S; Woods, A; Couchman, J R

    2000-01-01

    structure, where highly sulfated, iduronate-rich domains alternate with N-acetylated domains. Syndecan-4, a cell surface heparan sulfate proteoglycan, has a distinct role in cell adhesion, suggesting its chains may differ from those of other cell surface proteoglycans. To determine whether the specific role...... of syndecan-4 correlates with a distinct heparan sulfate structure, we have analyzed heparan sulfate chains from the different surface proteoglycans of a single fibroblast strain and compared their ability to bind the Hep II domain of fibronectin, a ligand known to promote focal adhesion formation...... through syndecan-4. Despite distinct molecular masses of glypican and syndecan glycosaminoglycans and minor differences in disaccharide composition and sulfation pattern, the overall proportion and distribution of sulfated regions and the affinity for the Hep II domain were similar. Therefore, adhesion...

  7. Two arginine residues in the substrate pocket predominantly control the substrate selectivity of thiocyanate hydrolase.

    Science.gov (United States)

    Yamanaka, Yasuaki; Arakawa, Takatoshi; Watanabe, Toshinori; Namima, Satoshi; Sato, Masa; Hori, Shota; Ohtaki, Akashi; Noguchi, Keiichi; Katayama, Yoko; Yohda, Masafumi; Odaka, Masafumi

    2013-07-01

    Thiocyanate hydrolase (SCNase) of Thiobacillus thioparus THI115 is a cobalt (Co)-containing enzyme that catalyzes the hydrolysis of thiocyanate (SCN⁻), a major component of wastewater from coke oven factories, to carbonyl sulfide and ammonia. Although SCNase exhibits high structural similarities to Co-type nitrile hydratase (NHase), including a unique Co³⁺ catalytic center with two oxidized Cys ligands, both SCNase and NHase exclusively catalyze only their own substrates. Based on the differences in the substrate-binding pockets of these enzymes, βArg90 and γArg136 of SCNase, with side chains extending toward the pocket, were separately substituted with Phe and Trp, the corresponding residues, respectively, in Co-type NHase. Both SCNase βArg90 and SCNase γArg136 mutants showed no SCN⁻ hydrolysis activity but did catalyze the hydration of nitriles. The estimated kcat values (∼2 s⁻¹) corresponded to approximately 0.2% of that of Co-type NHase for nitrile hydration and approximately 3% of that of wild-type SCNase for SCN⁻ hydrolysis. The crystal structure of SCNase γR136W is essentially identical to that of the wild-type, including the Co³⁺ center having Cys oxidations; the size of the substrate pocket was enlarged because of conformational changes on the side chains of the mutated residue. Discussion of the difference in the environments around the substrate-binding pockets among the wild-type and mutant SCNases and Co-type NHase strongly suggests that βArg90 and γArg136, positioned at the top of the Co³⁺ center, predominantly control the substrate selectivity of SCNase. PMID:23453853

  8. Reasons not to ''pocket shoot''

    International Nuclear Information System (INIS)

    The authors' large population of intravenous drug abusers (IVDA) has increasingly resorted to supraclavicular central venous injection for vascular access. Few reports of complications associated with the practice of supraclavicular ''pocket'' injection have appeared in the radiologic literature. This exhibit demonstrates the complications associated with this practice, including pneumothorax, mycotic aneurysm, arteriovenous fistual, jugular vein thrombosis, cellulitis, foreign body and neck abscess. In addition, they show examples of sternoclavicular osteomyelities. The anatomy of the ''pocket'' and the pathophysiology and radiographic manifestations of these complications are reviewed

  9. Unbound position II in MXCXXC metallochaperone model peptides impacts metal binding mode and reactivity: Distinct similarities to whole proteins.

    Science.gov (United States)

    Shoshan, Michal S; Dekel, Noa; Goch, Wojciech; Shalev, Deborah E; Danieli, Tsafi; Lebendiker, Mario; Bal, Wojciech; Tshuva, Edit Y

    2016-06-01

    The effect of position II in the binding sequence of copper metallochaperones, which varies between Thr and His, was investigated through structural analysis and affinity and oxidation kinetic studies of model peptides. A first Cys-Cu(I)-Cys model obtained for the His peptide at acidic and neutral pH, correlated with higher affinity and more rapid oxidation of its complex; in contrast, the Thr peptide with the Cys-Cu(I)-Met coordination under neutral conditions demonstrated weaker and pH dependent binding. Studies with human antioxidant protein 1 (Atox1) and three of its mutants where S residues were replaced with Ala suggested that (a) the binding affinity is influenced more by the binding sequence than by the protein fold (b) pH may play a role in binding reactivity, and (c) mutating the Met impacted the affinity and oxidation rate more drastically than did mutating one of the Cys, supporting its important role in protein function. Position II thus plays a dominant role in metal binding and transport. PMID:26901629

  10. Origin of melt pockets in mantle xenoliths from southern Patagonia, Argentina

    Science.gov (United States)

    Aliani, Paola; Ntaflos, Theodoros; Bjerg, Ernesto

    2009-12-01

    Peridotite mantle xenoliths collected north of Gobernador Gregores, Patagonia, affected by cryptic and modal metasomatism bear melt pockets of unusually large size. Melt pockets consist of second generation olivine (ol2), clinopyroxene (cpx2) and spinel (sp2) ± relict amphibole (amph) immersed in a yellowish vesicular glass matrix. Amphibole breakdown was responsible for melt pocket generation as suggested by textural evidence and proved by consistent mass-balance calculations: amph → cpx2 + ol2 + sp2 + melt. Composition of calculated amphibole in amphibole-free melt pockets is very similar to that measured in amphibole-bearing melt pockets from the same xenolith, i.e. amphibole was consumed in the melt pocket generation process. In melt pockets devoid of relict amphibole, mass-balance calculations show remarkable differences between the calculated amphibole and the measured amphibole compositions in melt pockets from the same xenolith. The participation of minor proportions of a consumed reactant phase could be a reasonable explanation. In some samples the calculated phase proportion of glass is in excess compared to modal estimations based on backscattered electron images, probably because a portion of the generated melt was able to migrate out of the melt pockets. Compositional inhomogeneity of cpx2 and variable Ti Kd in cpx2 vs. glass in the same melt pocket reflect fast nucleation and growth and disequilibrium crystallisation, respectively. This and the difference between forsterite content in calculated equilibrium olivine and second generation olivine, suggest that mineral equilibrium was inhibited by rapid quenching of melt pockets.

  11. IT governance a pocket guide

    CERN Document Server

    Calder, Alan

    2007-01-01

    This new downloadable pocket guide in the Practical IT Governance series, is designed to provide the reader with a basic understanding of how an organization's Information Technology supports and enables the achievement of its strategies and objectives.

  12. Mr Black'sPocket

    Institute of Scientific and Technical Information of China (English)

    耿志华

    2002-01-01

    ground and put that in his pocket too. He was very happy now. He stopped digging for a minute and shouted to his wife. "Elizabeth, come quickly. Someone's hidden(隐蔽) a lot of money in our garden and I' m finding it.”

  13. Newnes electronics assembly pocket book

    CERN Document Server

    Brindley, Keith

    2013-01-01

    Produced in association with the Engineering Training Authority with contributions from dozens of people in the electronics industry. The material covers common skills in electrical and electronic engineering and concentrates mainly on wiring and assembly. 'Newnes Electronics Assembly Pocket Book' is for electronics technicians, students and apprentices.

  14. Pocket dictionary of laboratory equipment

    International Nuclear Information System (INIS)

    This pocket dictionary contains the 2500 most common terms for scientific and technical equipment in chemical laboratories. It is a useful tool for those who are used to communicating in German and English, but have to learn the special terminology in this field. (orig.)

  15. Genome-wide mapping indicates that p73 and p63 co-occupy target sites and have similar dna-binding profiles in vivo.

    Directory of Open Access Journals (Sweden)

    Annie Yang

    Full Text Available BACKGROUND: The p53 homologs, p63 and p73, share approximately 85% amino acid identity in their DNA-binding domains, but they have distinct biological functions. PRINCIPAL FINDINGS: Using chromatin immunoprecipitation and high-resolution tiling arrays covering the human genome, we identify p73 DNA binding sites on a genome-wide level in ME180 human cervical carcinoma cells. Strikingly, the p73 binding profile is indistinguishable from the previously described binding profile for p63 in the same cells. Moreover, the p73:p63 binding ratio is similar at all genomic loci tested, suggesting that there are few, if any, targets that are specific for one of these factors. As assayed by sequential chromatin immunoprecipitation, p63 and p73 co-occupy DNA target sites in vivo, suggesting that p63 and p73 bind primarily as heterotetrameric complexes in ME180 cells. CONCLUSIONS: The observation that p63 and p73 associate with the same genomic targets suggest that their distinct biological functions are due to cell-type specific expression and/or protein domains that involve functions other than DNA binding.

  16. TclTk Pocket Reference

    CERN Document Server

    Raines, Paul

    1998-01-01

    The Tcl/Tk combination is increasingly popular because it lets you produce sophisticated graphical interfaces with a few easy commands, develop and change scripts quickly, and conveniently tie together existing utilities or programming libraries. The Tcl/Tk Pocket Reference,a handy reference guide to the basic Tcl language elements, Tcl and Tk commands, and Tk widgets, is a companion volume to Tcl/Tk in a Nutshell.

  17. Prince2 2009 edition a pocket guide

    CERN Document Server

    Hedeman, Bert

    2010-01-01

    This Pocket Guide supplies a summary of the PRINCE2 method, to provide a quick introduction as well as a structured overview of the method;Main target Group for this pocket guide is anyone who wants to get to know the method PRINCE2 or a methodical approach for project management. The book is also very useful for members of a project management team on a project using the PRINCE2 method. Furthermore this pocket guide can be used as literature for the preparation of the PRINCE2 2009 Edition Foundation exam;This pocket guide is based on PRINCE2 2009 Edition;This pocket book deals with processes,

  18. Vaccinia protein F12 has structural similarity to kinesin light chain and contains a motor binding motif required for virion export.

    Directory of Open Access Journals (Sweden)

    Gareth W Morgan

    2010-02-01

    Full Text Available Vaccinia virus (VACV uses microtubules for export of virions to the cell surface and this process requires the viral protein F12. Here we show that F12 has structural similarity to kinesin light chain (KLC, a subunit of the kinesin-1 motor that binds cargo. F12 and KLC share similar size, pI, hydropathy and cargo-binding tetratricopeptide repeats (TPRs. Moreover, molecular modeling of F12 TPRs upon the crystal structure of KLC2 TPRs showed a striking conservation of structure. We also identified multiple TPRs in VACV proteins E2 and A36. Data presented demonstrate that F12 is critical for recruitment of kinesin-1 to virions and that a conserved tryptophan and aspartic acid (WD motif, which is conserved in the kinesin-1-binding sequence (KBS of the neuronal protein calsyntenin/alcadein and several other cellular kinesin-1 binding proteins, is essential for kinesin-1 recruitment and virion transport. In contrast, mutation of WD motifs in protein A36 revealed they were not required for kinesin-1 recruitment or IEV transport. This report of a viral KLC-like protein containing a KBS that is conserved in several cellular proteins advances our understanding of how VACV recruits the kinesin motor to virions, and exemplifies how viruses use molecular mimicry of cellular components to their advantage.

  19. (-)-Rhazinilam and the diphenylpyridazinone NSC 613241: Two compounds inducing the formation of morphologically similar tubulin spirals but binding apparently to two distinct sites on tubulin.

    Science.gov (United States)

    Bai, Ruoli; Hamel, Ernest

    2016-08-15

    The most potent microtubule assembly inhibitor of newer diphenylpyridazinone derivatives examined was NSC 613241. Because NSC 613241 and (-)-rhazinilam also induce the formation of similar 2-filament spirals, these aberrant reactions were compared. Spiral formation with both compounds was enhanced by GTP and inhibited by GDP and by 15 other inhibitors of microtubule assembly. Similarly, microtubule assembly induced by paclitaxel or laulimalide is enhanced by GTP and inhibited by GDP and assembly inhibitors, but neither [(3)H]NSC 613241 nor [(3)H](-)-rhazinilam bound to microtubules or inhibited the binding of [(3)H]paclitaxel or [(3)H]peloruside A to microtubules. Differences in the pitch of aberrant polymers were found: NSC 613241-induced and (-)-rhazinilam-induced spirals had average repeats of 85 and 79-80 nm, respectively. We found no binding of [(3)H]NSC 613241 or [(3)H](-)-rhazinilam to αβ-tubulin dimer, but both compounds were incorporated into the polymers they induced in substoichiometric reactions, with as little as 0.1-0.2 mol compound/mol of tubulin, and no cross-inhibition by NSC 613241 or (-)-rhazinilam into spirals occurred. Under reaction conditions where neither compound induced spiral formation, both compounds together synergistically induced substantial spiral formation. We conclude that (-)-rhazinilam and NSC 613241 bind to different sites on tubulin that differ from binding sites for other antitubulin agents. PMID:27311615

  20. Windows Vista Administrator's Pocket Guide

    CERN Document Server

    Stanek, William R

    2007-01-01

    Portable and precise, this pocket-sized guide delivers immediate answers for the day-to-day administration of Windows Vista. Zero in on core support and maintenance tasks using quick-reference tables, instructions, and lists. You'll get the precise information you need to solve problems and get the job done-whether you're at your desk or in the field! Get fast facts to: Install and configure Windows Vista-and optimize the user workspaceMaintain operating system components, hardware devices, and driversCreate user and group accounts-and control rights and permissionsAdminister group policy se

  1. Newnes electronics engineers pocket book

    CERN Document Server

    Brindley, Keith

    2013-01-01

    This book is packed with information and material which everyone involved in electronics will find indispensable. Now when you need to know a transistor's characteristics, or an integrated circuit's pinout details, simply look it up! The book is full of tables, symbols, formulae, conversions and illustrations.Promotion via the new Newnes Pocket Book catalogue to the electronics trade will drive sales into the book trade Covers component data; encapsulations; pin-outs; symbols & codings Extensive material on conversion factors, formulae; units and relationships

  2. Electrical engineering a pocket reference

    CERN Document Server

    Schmidt-Walter, Heinz

    2007-01-01

    This essential reference offers you a well-organized resource for accessing the basic electrical engineering knowledge you need for your work. Whether you're an experienced engineer who appreciates an occasional refresher in key areas, or a student preparing to enter the field, Electrical Engineering: A Pocket Reference provides quick and easy access to fundamental principles and their applications. You also find an extensive collection of time-saving equations that help simplify your daily projects.Supported with more than 500 diagrams and figures, 60 tables, and an extensive index, this uniq

  3. Oracle Data Dictionary Pocket Reference

    CERN Document Server

    Kreines, David

    2003-01-01

    If you work with Oracle, then you don't need to be told that the data dictionary is large and complex, and grows larger with each new Oracle release. It's one of the basic elements of the Oracle database you interact with regularly, but the sheer number of tables and views makes it difficult to remember which view you need, much less the name of the specific column. Want to make it simpler? The Oracle Data Dictionary Pocket Reference puts all the information you need right at your fingertips. Its handy and compact format lets you locate the table and view you need effortlessly without stoppin

  4. JavaScript Pocket Reference

    CERN Document Server

    Flanagan, David

    1998-01-01

    JavaScript is a powerful, object-based scripting language that can be embedded directly in HTML pages. It allows you to create dynamic, interactive Web-based applications that run completely within a Web browser -- JavaScript is the language of choice for developing Dynamic HTML (DHTML) content. JavaScript can be integrated effectively with CGI and Java to produce sophisticated Web applications, although, in many cases, JavaScript eliminates the need for complex CGI scripts and Java applets altogether. The JavaScript Pocket Reference is a companion volume to JavaScript: The Definitive Guide

  5. Exploration of electrostatic interaction in the hydrophobic pocket of lysozyme: Importance of ligand-induced perturbation of the secondary structure on the mode of binding of exogenous ligand and possible consequences.

    Science.gov (United States)

    Panja, Sudipta; Halder, Mintu

    2016-08-01

    Exogenous ligand binding can be adequate to alter the secondary structure of biomolecules besides other external stimuli. In such cases, structural alterations can complicate on the nature of interaction with the exogenous molecules. In order to accommodate the exogenous ligand, the biomolecule has to unfold resulting in a considerable change to its properties. If the bound ligand can be unbound, the biomolecule gets the opportunity to refold back and return to its native state. Keeping this in mind, we have purposely investigated the interaction of tartrazine (TZ), a well abundant azo food colorant, with two homologous lysozymes, namely, human lysozyme (HLZ) and chicken egg white lysozyme (CEWLZ) in physiological pH condition. The binding of TZ with lysozymes has been identified to accompany a ligand-induced secondary structure alteration as indicated by the circular dichroism spectra, and the reduction of α-helical content is more with HLZ than CEWLZ. Interestingly, the binding is identified to occur in the electronic ground state of TZ with lysozyme in its hydrophobic cavity, containing excess of positive charge, predominantly via electrostatic interaction. With increase of salinity of the medium the protein tends to refold back due to wakening of electrostatic forces and consequent reduction of strength of ligand interaction and unbinding. The entropy enthalpy compensation (EEC) has been probed to understand the binding features and it is found that CEWLZ-TZ shows better compensation than HLZ-TZ complex. This is presumably due to the fact that with CEWLZ the binding does not accompany substantial change in the protein secondary structure and hence ineffective to scramble the EEC. The present study initiates the importance of ligand-perturbed structural alteration of biomolecule in controlling the thermodynamics of binding. If there is a considerable alteration of the protein secondary structure due to binding, it is indicative that such changes should bring in

  6. In silico peptide-binding predictions of passerine MHC class I reveal similarities across distantly related species, suggesting convergence on the level of protein function

    DEFF Research Database (Denmark)

    Follin, Elna; Karlsson, Maria; Lundegaard, Claus; Nielsen, Morten; Wallin, Stefan; Paulsson, Kajsa Maria; Westerdahl, Helena

    2013-01-01

    The major histocompatibility complex (MHC) genes are the most polymorphic genes found in the vertebrate genome, and they encode proteins that play an essential role in the adaptive immune response. Many songbirds (passerines) have been shown to have a large number of transcribed MHC class I genes...... compared to most mammals. To elucidate the reason for this large number of genes, we compared 14 MHC class I alleles (α1–α3 domains), from great reed warbler, house sparrow and tree sparrow, via phylogenetic analysis, homology modelling and in silico peptide-binding predictions to investigate their...... functional significance. The MHC class I allomorphs from house sparrow and tree sparrow, species that diverged 10 million years ago (MYA), had overlapping peptide-binding specificities, and these similarities across species were also confirmed in phylogenetic analyses based on amino acid sequences. Notably...

  7. Identification of active pocket and protein druggability within envelope glycoprotein GP2 from Ebola virus

    Institute of Scientific and Technical Information of China (English)

    Beuy; Joob; Viroj; Wiwanitkit

    2014-01-01

    The drug searching for combating the present outbreak of Ebola virus infection is the urgent activity at present.Finding the new effective drug at present must base on the molecular analysis of the pathogenic virus.The in-depth analysis of the viral protein to find the binding site,active pocket is needed.Here,the authors analyzed the envelope glycoprotein GP2 from Ebola virus.Identification of active pocket and protein draggability within envelope glycoprotein GP2 from Ebola virus was done.According to this assessment,7 active pockets with varied draggability could be identified.

  8. Identification of active pocket and protein druggability within envelope glycoprotein GP2 from Ebola virus

    Institute of Scientific and Technical Information of China (English)

    Beuy Joob; Viroj Wiwanitkit

    2014-01-01

    The drug searching for combating the present outbreak of Ebola virus infection is the urgent activity at present. Finding the new effective drug at present must base on the molecular analysis of the pathogenic virus. The in-depth analysis of the viral protein to find the binding site, active pocket is needed. Here, the authors analyzed the envelope glycoprotein GP2 from Ebola virus. Identification of active pocket and protein druggability within envelope glycoprotein GP2 from Ebola virus was done. According to this assessment, 7 active pockets with varied druggability could be identified.

  9. The system architecture of the Pocket Companion

    OpenAIRE

    Paul J. M. Havinga; Smit, Gerard J. M.

    1997-01-01

    In the Moby Dick project we design the architecture of a so-called Pocket Companion. It is a small personal portable computer with wireless communication facilities for every day use. The typical use of the Pocket Companion induces a number of requirements concerning security, performance, energy consumption, communication and size. We have shown that these requirements are interrelated and can only be met optimal with one single architecture. The Pocket Companion architecture consists of a c...

  10. The pocket dictionary of energy

    International Nuclear Information System (INIS)

    The pocket dictionary of energy does not only address the interested amateur but also students, pupils, teachers, scientists, technicians, and polititcians in like manner. The dictionary contains ca. 900 key-words from the fields of energy, consumption, energy types, energy deposits, energy programmes, energy industry, thermal insulation, governmental aids for energy conservation measures, heating cost calculation, energy utilization and energy conservation. The problems of the costs and efficiency of energy conversion, energy pricing, the promotion of research projects, the rentability of heating devices or insulation, the sanitation of old buildings, governmental aids by subsidies or tax abatement according to the modernization and energy conservation law etc., as well as the problem of pollution and the endangering of the environment by exhaust air, waste heat, ash and litter are emphasized particularly. Considering the space available the criterion for the selection of the key-words was not a scientific completeness but the provision of a fundamental understanding of the matter. (orig.)

  11. Clinical characteristics of the eardrum retraction pocket

    Directory of Open Access Journals (Sweden)

    Ješić Snežana

    2003-01-01

    Full Text Available Development of the eardrum retraction pocket, as pathologic finding, depends on Eustachian tube dysfunction, onset of the middle ear infection and site of development of retraction on the eardrum. The study is aimed at: 1. Determining the incidence of eardrum retraction pocket and cholesteatoma within it, as well as at the degree of eardrum retraction; 2. Determining of association between eardrum retraction pocket and changes of the eardrum mucosaand parstensa of the tympanic membrane; 3. Determining of onset and intensity of the bone destruction in eardrum retraction pocket; 4. Examining of Eustachian tube function based on time of mucocilliary transport according to the type of the eardrum retraction pocket. The study is based on the retrospective analysis of the results obtained from the patients treated at the Institute of Oto-Rhino-Laryngology and Maxillofacial Surgery Clinical Centre of Serbia in Belgrade for the diagnosis of the chronic suppurative otitis who underwent otosurgical procedures during the six-year period, from 1996-2001. In our series of 540 patients subjected to otosurgical treatment, the incidence of the retraction pocket of the eardrum was 11.23%. Onset of more severe degree of eardrum retraction was most frequent in the attic. Cholesteatoma was detected in 82.2% of patients of the group with the attic-retraction pocket of the eardrum, as well as in 25% of patients of the group of tensa-sinus retraction pocket of the eardrum. Atrophic changes of the tympanic membrane pars tensa were detected in almost all tensa-sinus retraction pockets of the eardrum. Approximately one half of the attic-retraction pockets of the eardrum were accompanied by eardrum atrophy. Bone destruction of the auditory ossicles was limited to the long process of incus and superior structures of stapes. Time of the mucocilliary transport was significantly longer (p<0.01 in attic-retraction pocket of the eardrum than in tensa-sinus retraction pocket of

  12. Single-chain antibody-fragment M6P-1 possesses a mannose 6-phosphate monosaccharide-specific binding pocket that distinguishes N-glycan phosphorylation in a branch-specific manner†.

    Science.gov (United States)

    Blackler, Ryan J; Evans, Dylan W; Smith, David F; Cummings, Richard D; Brooks, Cory L; Braulke, Thomas; Liu, Xinyu; Evans, Stephen V; Müller-Loennies, Sven

    2016-02-01

    The acquisition of mannose 6-phosphate (Man6P) on N-linked glycans of lysosomal enzymes is a structural requirement for their transport from the Golgi apparatus to lysosomes mediated by the mannose 6-phosphate receptors, 300 kDa cation-independent mannose 6-phosphate receptor (MPR300) and 46 kDa cation-dependent mannose 6-phosphate receptor (MPR46). Here we report that the single-chain variable domain (scFv) M6P-1 is a unique antibody fragment with specificity for Man6P monosaccharide that, through an array-screening approach against a number of phosphorylated N-glycans, is shown to bind mono- and diphosphorylated Man6 and Man7 glycans that contain terminal αMan6P(1 → 2)αMan(1 → 3)αMan. In contrast to MPR300, scFv M6P-1 does not bind phosphodiesters, monophosphorylated Man8 or mono- or diphosphorylated Man9 structures. Single crystal X-ray diffraction analysis to 2.7 Å resolution of Fv M6P-1 in complex with Man6P reveals that specificity and affinity is achieved via multiple hydrogen bonds to the mannose ring and two salt bridges to the phosphate moiety. In common with both MPRs, loss of binding was observed for scFv M6P-1 at pH values below the second pKa of Man6P (pKa = 6.1). The structures of Fv M6P-1 and the MPRs suggest that the change of the ionization state of Man6P is the main driving force for the loss of binding at acidic lysosomal pH (e.g. lysosome pH ∼ 4.6), which provides justification for the evolution of a lysosomal enzyme transport pathway based on Man6P recognition. PMID:26503547

  13. Crystal Structure of the Bovine lactadherin C2 Domain, a Membrane Binding Motif, Shows Similarity of the C2 Domains of Factor V and Factor VIII

    Energy Technology Data Exchange (ETDEWEB)

    Lin,L.; Huai, Q.; Huang, M.; Furie, B.; Furie, B.

    2007-01-01

    Lactadherin, a glycoprotein secreted by a variety of cell types, contains two EGF domains and two C domains with sequence homology to the C domains of blood coagulation proteins factor V and factor VIII. Like these proteins, lactadherin binds to phosphatidylserine (PS)-containing membranes with high affinity. We determined the crystal structure of the bovine lactadherin C2 domain (residues 1 to 158) at 2.4 Angstroms. The lactadherin C2 structure is similar to the C2 domains of factors V and VIII (rmsd of C? atoms of 0.9 Angstroms and 1.2 Angstroms, and sequence identities of 43% and 38%, respectively). The lactadherin C2 domain has a discoidin-like fold containing two ?-sheets of five and three antiparallel ?-strands packed against one another. The N and C termini are linked by a disulfide bridge between Cys1 and Cys158. One ?-turn and two loops containing solvent-exposed hydrophobic residues extend from the C2 domain ?-sandwich core. In analogy with the C2 domains of factors V and VIII, some or all of these solvent-exposed hydrophobic residues, Trp26, Leu28, Phe31, and Phe81, likely participate in membrane binding. The C2 domain of lactadherin may serve as a marker of cell surface phosphatidylserine exposure and may have potential as a unique anti-thrombotic agent.

  14. Crystal Structure of the Bovine lactadherin C2 Domain, a Membrane Binding Motif, Shows Similarity to the C2 Domains of Factor V and Factor VIII

    Energy Technology Data Exchange (ETDEWEB)

    Lin,L.

    2007-01-01

    Lactadherin, a glycoprotein secreted by a variety of cell types, contains two EGF domains and two C domains with sequence homology to the C domains of blood coagulation proteins factor V and factor VIII. Like these proteins, lactadherin binds to phosphatidylserine (PS)-containing membranes with high affinity. We determined the crystal structure of the bovine lactadherin C2 domain (residues 1 to 158) at 2.4 {angstrom}. The lactadherin C2 structure is similar to the C2 domains of factors V and VIII (rmsd of C{sub {alpha}} atoms of 0.9 {angstrom} and 1.2 {angstrom}, and sequence identities of 43% and 38%, respectively). The lactadherin C2 domain has a discoidin-like fold containing two {beta}-sheets of five and three antiparallel {beta}-strands packed against one another. The N and C termini are linked by a disulfide bridge between Cys1 and Cys158. One {beta}-turn and two loops containing solvent-exposed hydrophobic residues extend from the C2 domain {beta}-sandwich core. In analogy with the C2 domains of factors V and VIII, some or all of these solvent-exposed hydrophobic residues, Trp26, Leu28, Phe31, and Phe81, likely participate in membrane binding. The C2 domain of lactadherin may serve as a marker of cell surface phosphatidylserine exposure and may have potential as a unique anti-thrombotic agent.

  15. Pocket companion to PMI's PMBOK guide

    CERN Document Server

    Snijders, Paul; Zandhuis, Anton

    2010-01-01

    This pocket guide is based on the PMBOK Guide® Fourth Edition.This pocket guide supplies a summary of the PMBOK Guide® , to provide a quick introduction as well as a structured overview of this method for project management.This pocket guide deals with the key issues and themes within project management and PMBOK:A short overview of the activities of PMI Inc., The organization and its standards: PMBOK Guide®, Standard for Project Portfolio Management, Standard for Program Management, OPM3.The essentials of the Project Lifecycle and Organization.What are the key project management knowledge ar

  16. Triple NF-kB binding sites and LTR sequence similarities in HIV-1C isolates irrespective of helminth co-infection

    Science.gov (United States)

    2014-01-01

    Background Helminth infections as well as structural alternations in the long-terminal repeat (LTR) regions of HIV-1 are known to contribute to elevated HIV RNA level and enhance HIV-1 diseases progression. However, the impact of helminths infections on the occurrences of triple NF-κB and genetic variability in LTR region of HIV-1C isolates is not known. We aimed to examine the presence of genetic variability in the LTR region of HIV-1C isolates during chronic HIV-helminth co-infection. Methods HIV-1C infected Ethiopians with (n = 22) and without (n = 20) helminth infection were included. The LTR region of HIV was amplified and sequenced. Sequences were aligned with reference set from the Los Alamos HIV database. Phylogenetic analysis and frequency of polymorphic changes was performed by the neighbour-joining method using Geneious Basic software. Results All LTR sequences from patients with or without of helminth co-infection clustered with HIV-1 subtype C with two distinct subclusters (C and C’). The enhancer element was found to have three copies of 10-base pair binding sites for NF-κBs which is an evidence for predominance of triple NF-κB sites (94%) in HIV-1C isolates irrespective of helminths co-infection and subclusters. Moreover, irrespective of helminth co-infection and C/C’ subclusters high sequences similarity in LTR was observed. There was no significant difference in plasma HIV RNA level between HIV-1 C and C’ subclusters. Conclusions Despite the small sample size, the predominance of triple NF-κB binding sites and high sequence similarities in LTR region irrespective of helminths infection suggest the natural occurrence of the three NF-κB binding sites in HIV-1C isolates without the influence of secondary infection. Thus, the higher HIV-1C viraemia in helminth co-infected individuals is more likely a result of immune activation rather than LTR sequence variation. Moreover, the lack of significant difference in plasma HIV RNA level

  17. Parameter selection of pocket extraction algorithm using interaction interface

    Institute of Scientific and Technical Information of China (English)

    KIM Chong-Min; WON Chung-In; RYU Joonghyun; CHO Cheol-Hyung; BHAK Jonghwa; KIM Deok-Soo

    2006-01-01

    Pockets in proteins have been known to be very important for the life process. There have been several studies in the past to automatically extract the pockets from the structure information of known proteins. However, it is difficult to find a study comparing the precision of the extracted pockets from known pockets on the protein. In this paper, we propose an algorithm for extracting pockets from structure data of proteins and analyze the quality of the algorithm by comparing the extracted pockets with some known pockets. These results in this paper can be used to set the parameter values of the pocket extraction algorithm for getting better results.

  18. Macintosh Troubleshooting Pocket Guide for Mac OS

    CERN Document Server

    Lerner, David; Corporation, Tekserve

    2009-01-01

    The Macintosh Troubleshooting Pocket Guide covers the most common user hardware and software trouble. It's not just a book for Mac OS X (although it includes tips for OS X and Jaguar), it's for anyone who owns a Mac of any type-- there are software tips going back as far as OS 6. This slim guide distills the answers to the urgent questions that Tekserve's employee's answer every week into a handy guide that fits in your back pocket or alongside your keyboard.

  19. Cell-phone interference with pocket dosimeters

    International Nuclear Information System (INIS)

    Accurate reporting of personal dose is required by regulation for hospital personnel that work with radioactive material. Pocket dosimeters are commonly used for monitoring this personal dose. We show that operating a cell phone in the vicinity of a pocket dosimeter can introduce large and erroneous readings of the dosimeter. This note reports a systematic study of this electromagnetic interference. We found that simple practical measures are enough to mitigate this problem, such as increasing the distance between the cell phone and the dosimeter or shielding the dosimeter, while maintaining its sensitivity to ionizing radiation, by placing it inside a common anti-static bag. (note)

  20. Bacterial periplasmic sialic acid-binding proteins exhibit a conserved binding site

    Energy Technology Data Exchange (ETDEWEB)

    Gangi Setty, Thanuja [Institute for Stem Cell Biology and Regenerative Medicine, NCBS Campus, GKVK Post, Bangalore, Karnataka 560 065 (India); Cho, Christine [Carver College of Medicine, University of Iowa, Iowa City, IA 52242-1109 (United States); Govindappa, Sowmya [Institute for Stem Cell Biology and Regenerative Medicine, NCBS Campus, GKVK Post, Bangalore, Karnataka 560 065 (India); Apicella, Michael A. [Carver College of Medicine, University of Iowa, Iowa City, IA 52242-1109 (United States); Ramaswamy, S., E-mail: ramas@instem.res.in [Institute for Stem Cell Biology and Regenerative Medicine, NCBS Campus, GKVK Post, Bangalore, Karnataka 560 065 (India)

    2014-07-01

    Structure–function studies of sialic acid-binding proteins from F. nucleatum, P. multocida, V. cholerae and H. influenzae reveal a conserved network of hydrogen bonds involved in conformational change on ligand binding. Sialic acids are a family of related nine-carbon sugar acids that play important roles in both eukaryotes and prokaryotes. These sialic acids are incorporated/decorated onto lipooligosaccharides as terminal sugars in multiple bacteria to evade the host immune system. Many pathogenic bacteria scavenge sialic acids from their host and use them for molecular mimicry. The first step of this process is the transport of sialic acid to the cytoplasm, which often takes place using a tripartite ATP-independent transport system consisting of a periplasmic binding protein and a membrane transporter. In this paper, the structural characterization of periplasmic binding proteins from the pathogenic bacteria Fusobacterium nucleatum, Pasteurella multocida and Vibrio cholerae and their thermodynamic characterization are reported. The binding affinities of several mutations in the Neu5Ac binding site of the Haemophilus influenzae protein are also reported. The structure and the thermodynamics of the binding of sugars suggest that all of these proteins have a very well conserved binding pocket and similar binding affinities. A significant conformational change occurs when these proteins bind the sugar. While the C1 carboxylate has been identified as the primary binding site, a second conserved hydrogen-bonding network is involved in the initiation and stabilization of the conformational states.

  1. Bacterial periplasmic sialic acid-binding proteins exhibit a conserved binding site

    International Nuclear Information System (INIS)

    Structure–function studies of sialic acid-binding proteins from F. nucleatum, P. multocida, V. cholerae and H. influenzae reveal a conserved network of hydrogen bonds involved in conformational change on ligand binding. Sialic acids are a family of related nine-carbon sugar acids that play important roles in both eukaryotes and prokaryotes. These sialic acids are incorporated/decorated onto lipooligosaccharides as terminal sugars in multiple bacteria to evade the host immune system. Many pathogenic bacteria scavenge sialic acids from their host and use them for molecular mimicry. The first step of this process is the transport of sialic acid to the cytoplasm, which often takes place using a tripartite ATP-independent transport system consisting of a periplasmic binding protein and a membrane transporter. In this paper, the structural characterization of periplasmic binding proteins from the pathogenic bacteria Fusobacterium nucleatum, Pasteurella multocida and Vibrio cholerae and their thermodynamic characterization are reported. The binding affinities of several mutations in the Neu5Ac binding site of the Haemophilus influenzae protein are also reported. The structure and the thermodynamics of the binding of sugars suggest that all of these proteins have a very well conserved binding pocket and similar binding affinities. A significant conformational change occurs when these proteins bind the sugar. While the C1 carboxylate has been identified as the primary binding site, a second conserved hydrogen-bonding network is involved in the initiation and stabilization of the conformational states

  2. Frameworks for IT management a pocket guide

    CERN Document Server

    Rozemeijer, Eric

    2008-01-01

    This Pocket Guide is a concise summary of the Frameworks for IT Management. A quick, portable reference tool to the standards used within the Service Management community.English version available: September 2007, Dutch, French, Japanese, Spanish, German available February 2008.

  3. E-mail security a pocket guide

    CERN Document Server

    Furnell, Steven

    2010-01-01

    This pocket guide will help businesses to address the most important issues. Its comprehensive approach covers both the technical and the managerial aspects of the subject, offering valuable insights for IT professionals, managers and executives, as well as for individual users of e-mail.

  4. Evidence for designing health promoting pocket parks

    DEFF Research Database (Denmark)

    Peschardt, Karin Kragsig; Stigsdotter, Ulrika K.

    2014-01-01

    pocket park, Dantes Plads, before and after a redesign. Six people were interviewed about their perception of the change. First of all, the results show that Dantes Plads is primarily used for ‘rest and restitution’. Furthermore, the interviewees prefer to have the presence of sun, shade and planting in...

  5. Pocket Checklists of Indonesian timber trees

    NARCIS (Netherlands)

    Prawira, Soewanda A.; Tantra, I.G.M.; Whitmore, T.C.

    1984-01-01

    Indonesia as yet does not have a comprehensive account of the forest trees which reach timber size (35 cm dbh = 14 inch or 105 cm gbh = 42 inch). A project has been started in August 1983 by the Botany Section of the Forest Research Institute in Bogor, Indonesia, to prepare pocket checklists of the

  6. The U1 RNA-binding site of the U1 small nuclear ribonucleoprotein (snRNP)-associated A protein suggests a similarity with U2 snRNPs.

    OpenAIRE

    Lutz-Freyermuth, C; Keene, J D; Lutz-Reyermuth, C

    1989-01-01

    The site of interaction between human U1 RNA and one of its uniquely associated proteins, A, was examined with in vitro binding assays. The A protein bound directly to stem-loop II of U1 RNA in a region which exhibits sequence similarity to U2 RNA. The similarity with U2 RNA was in a region that has been shown to interact with a U2 RNA-associated protein. The A protein-binding site on U1 RNA overlapped a previously described epitope for an RNA-specific human autoantibody (S. L. Deutscher and ...

  7. A strategy using NMR peptide structures of thromboxane A2 receptor as templates to construct ligand-recognition pocket of prostacyclin receptor

    Directory of Open Access Journals (Sweden)

    Ruan Ke-He

    2005-11-01

    Full Text Available Abstract Background: Prostacyclin receptor (IP and thromboxane A2 receptor (TP belong to rhodopsin-type G protein-coupling receptors and respectively bind to prostacyclin and thromboxane A2 derived from arachidonic acid. Recently, we have determined the extracellular loop (eLP structures of the human TP receptor by 2-D 1H NMR spectroscopy using constrained peptides mimicking the individual eLP segments. The studies have identified the segment along with several residues in the eLP domains important to ligand recognition, as well as proposed a ligand recognition pocket for the TP receptor. Results: The IP receptor shares a similar primary structure in the eLPs with those of the TP receptor. Forty percent residues in the second eLPs of the receptors are identical, which is the major region involved in forming the ligand recognition pocket in the TP receptor. Based on the high homology score, the eLP domains of the IP receptor were constructed by the homology modeling approach using the NMR structures of the TP eLPs as templates, and then configured to the seven transmembrane (TM domains model constructed using the crystal structure of the bovine rhodopsin as a template. A NMR structure of iloprost was docked into the modeled IP ligand recognition pocket. After dynamic studies, the segments and residues involved in the IP ligand recognition were proposed. A key residue, Arg173 involved in the ligand recognition for the IP receptor, as predicted from the modeling, was confirmed by site-directed mutagenesis. Conclusion: A 3-D model of the human IP receptor was constructed by homology modeling using the crystal structure of bovine rhodopsin TM domains and the NMR structures of the synthetic constrained peptides of the eLP domains of the TP receptor as templates. This strategy can be applied to molecular modeling and the prediction of ligand recognition pockets for other prostanoid receptors.

  8. Structural and Functional Studies Indicate That the EPEC Effector, EspG, Directly Binds p21-Activated Kinase

    Energy Technology Data Exchange (ETDEWEB)

    Germane, Katherine L.; Spiller, Benjamin W. (Vanderbilt)

    2011-09-20

    Bacterial pathogens secrete effectors into their hosts that subvert host defenses and redirect host processes. EspG is a type three secretion effector with a disputed function that is found in enteropathogenic Escherichia coli. Here we show that EspG is structurally similar to VirA, a Shigella virulence factor; EspG has a large, conserved pocket on its surface; EspG binds directly to the amino-terminal inhibitory domain of human p21-activated kinase (PAK); and mutations to conserved residues in the surface pocket disrupt the interaction with PAK.

  9. Distributed classification for pocket data mining

    OpenAIRE

    Stahl, F.; Gaber, M; Liu, Han; Bramer, Max; Yu, P.

    2011-01-01

    Distributed and collaborative data stream mining in a mobile computing environment is referred to as Pocket Data Mining PDM. Large amounts of available data streams to which smart phones can subscribe to or sense, coupled with the increasing computational power of handheld devices motivates the development of PDM as a decision making system. This emerging area of study has shown to be feasible in an earlier study using technological enablers of mobile software agents and stream mining techniq...

  10. Windows® 7 Administrator's Pocket Consultant

    CERN Document Server

    Stanek, William

    2009-01-01

    Portable and precise, this pocket-sized guide delivers immediate answers for the day-to-day administration of Windows 7-from desktop configuration and management to networking and security issues. Zero in on core support and maintenance tasks by using quick-reference tables, instructions, and lists. You'll get the precise information you need to solve problems and get the job done-whether at your desk or in the field!

  11. ISO27001 / ISO27002 a pocket guide

    CERN Document Server

    Calder, Alan

    2013-01-01

    Information is one of your organisation's most important resources. Keeping it secure is therefore vital to your business. This handy pocket guide is an essential overview of two key information security standards that cover the formal requirements (ISO27001:2013) for creating an Information Security Management System (ISMS), and the best-practice recommendations (ISO27002:2013) for those responsible for initiating, implementing or maintaining it.

  12. Pocket Checklists of Indonesian timber trees

    OpenAIRE

    Prawira, Soewanda A.; Tantra, I.G.M.; Whitmore, T.C.

    1984-01-01

    Indonesia as yet does not have a comprehensive account of the forest trees which reach timber size (35 cm dbh = 14 inch or 105 cm gbh = 42 inch). A project has been started in August 1983 by the Botany Section of the Forest Research Institute in Bogor, Indonesia, to prepare pocket checklists of the timber trees of all regions of the country. These lists will include forest-based descriptions, keys and line drawings.

  13. Newnes radio and electronics engineer's pocket book

    CERN Document Server

    Moorshead, H W; Perry, J

    1978-01-01

    Newnes Radio and Electronics Engineer's Pocket Book, Fifteenth Edition provides reference of the information relevant in radio and electronics engineering. The book presents tables, illustrations, and diagrams of various data used in radio and electronics engineering. The coverage of the text includes abbreviations and symbols, electrical equations, and code conversions. The text will be useful to engineers, technicians, and other professionals who require a reference about the different aspects of radio and electronics.

  14. SAS1 and SAS2, GTP-binding protein genes in Dictyostelium discoideum with sequence similarities to essential genes in Saccharomyces cerevisiae.

    OpenAIRE

    Saxe, S A; Kimmel, A R

    1990-01-01

    We have identified two novel, very closely related genes, SAS1 and SAS2, from Dictyostelium discoideum. These encode small, approximately 20-kilodaton proteins with amino acid sequences thought to be involved in interaction with guanine nucleotides. The protein sizes, spacings of GTP-binding domains, and carboxyl-terminal sequences suggest their relationship to the ubiquitous ras-type proteins. Their sequences, however, are sufficiently different to indicate that they are not true ras protein...

  15. Characterization of polymer release from the flagellar pocket of Leishmania mexicana promastigotes.

    Science.gov (United States)

    Stierhof, Y D; Ilg, T; Russell, D G; Hohenberg, H; Overath, P

    1994-04-01

    Trypanosomatids contain a unique compartment, the flagellar pocket, formed by an invagination of the plasma membrane at the base of the flagellum, which is considered to be the sole cellular site for endocytosis and exocytosis of macromolecules. The culture supernatant of Leishmania mexicana promastigotes, the insect stage of this protozoan parasite, contains two types of polymers: a filamentous acid phosphatase (sAP) composed of a 100-kD phosphoglycoprotein with non-covalently associated proteo high molecular weight phosphoglycan (proteo-HMWPG) and fibrous material termed network consisting of complex phosphoglycans. Secretion of both polymers is investigated using mAbs and a combination of light and electron microscopic techniques. Long filaments of sAP are detectable in the lumen of the flagellar pocket. Both sAP filaments and network material emerge from the ostium of the flagellar pocket. While sAP filaments detach from the cells, the fibrous network frequently remains associated with the anterior end of the parasites and can be found in the center of cell aggregates. The related species L. major forms similar networks. Since polymeric structures cannot be detected in intracellular compartments, it is proposed that monomeric or, possibly, oligomeric subunits synthesized in the cells are secreted into the flagellar pocket. Polymer formation from subunits is suggested to occur in the lumen of the pocket before release into the culture medium or, naturally, into the gut of infected sandflies. PMID:8163549

  16. Flagellar pocket restructuring through the Leishmania life cycle involves a discrete flagellum attachment zone.

    Science.gov (United States)

    Wheeler, Richard J; Sunter, Jack D; Gull, Keith

    2016-02-15

    Leishmania promastigote parasites have a flagellum, which protrudes from the flagellar pocket at the cell anterior, yet, surprisingly, have homologs of many flagellum attachment zone (FAZ) proteins--proteins used in the related Trypanosoma species to laterally attach the flagellum to the cell body from the flagellar pocket to the cell posterior. Here, we use seven Leishmania mexicana cell lines that expressed eYFP fusions of FAZ protein homologs to show that the Leishmania flagellar pocket includes a FAZ structure. Electron tomography revealed a precisely defined 3D organisation for both the flagellar pocket and FAZ, with striking similarities to those of Trypanosoma brucei. Expression of two T. brucei FAZ proteins in L. mexicana showed that T. brucei FAZ proteins can assemble into the Leishmania FAZ structure. Leishmania therefore have a previously unrecognised FAZ structure, which we show undergoes major structural reorganisation in the transition from the promastigote (sandfly vector) to amastigote (in mammalian macrophages). Morphogenesis of the Leishmania flagellar pocket, a structure important for pathogenicity, is therefore intimately associated with a FAZ; a finding with implications for understanding shape changes involving component modules during evolution. PMID:26746239

  17. Holo- And Apo- Structures of Bacterial Periplasmic Heme Binding Proteins

    Energy Technology Data Exchange (ETDEWEB)

    Ho, W.W.; Li, H.; Eakanunkul, S.; Tong, Y.; Wilks, A.; Guo, M.; Poulos, T.L.

    2009-06-01

    An essential component of heme transport in Gram-negative bacterial pathogens is the periplasmic protein that shuttles heme between outer and inner membranes. We have solved the first crystal structures of two such proteins, ShuT from Shigella dysenteriae and PhuT from Pseudomonas aeruginosa. Both share a common architecture typical of Class III periplasmic binding proteins. The heme binds in a narrow cleft between the N- and C-terminal binding domains and is coordinated by a Tyr residue. A comparison of the heme-free (apo) and -bound (holo) structures indicates little change in structure other than minor alterations in the heme pocket and movement of the Tyr heme ligand from an 'in' position where it can coordinate the heme iron to an 'out' orientation where it points away from the heme pocket. The detailed architecture of the heme pocket is quite different in ShuT and PhuT. Although Arg{sup 228} in PhuT H-bonds with a heme propionate, in ShuT a peptide loop partially takes up the space occupied by Arg{sup 228}, and there is no Lys or Arg H-bonding with the heme propionates. A comparison of PhuT/ShuT with the vitamin B{sub 12}-binding protein BtuF and the hydroxamic-type siderophore-binding protein FhuD, the only two other structurally characterized Class III periplasmic binding proteins, demonstrates that PhuT/ShuT more closely resembles BtuF, which reflects the closer similarity in ligands, heme and B{sub 12}, compared with ligands for FhuD, a peptide siderophore.

  18. The Binding Mode Prediction and Similar Ligand Potency in the Active Site of Vitamin D Receptor with QM/MM Interaction, MESP, and MD Simulation.

    Science.gov (United States)

    Selvaraman, Nagamani; Selvam, Saravana Kumar; Muthusamy, Karthikeyan

    2016-08-01

    Non-secosteroidal ligands are well-known vitamin D receptor (VDR) agonists. In this study, we described a combined QM/MM to define the protein-ligand interaction energy a strong positive correlation in both QM-MM interaction energy and binding free energy against the biological activity. The molecular dynamics simulation study was performed, and specific interactions were extensively studied. The molecular docking results and surface analysis shed light on steric and electrostatic complementarities of these non-secosteroidal ligands to VDR. Finally, the drug likeness properties were also calculated and found within the acceptable range. The results show that bulky group substitutions in side chain decrease the VDR activity, whereas a small substitution increased it. Functional analyses of H393A and H301A mutations substantiate their roles in the VDR agonistic and antagonistic activities. Apart from the His393 and His301, two other amino acids in the hinge region viz. Ser233 and Arg270 acted as an electron donor/acceptor specific to the agonist in the distinct ligand potency. The results from this study disclose the binding mechanism of VDR agonists and structural modifications required to improve the selectivity. PMID:26945790

  19. Pardon my French pocket French slang dictionary

    CERN Document Server

    Nicholson, Kate

    2009-01-01

    A runaway bestseller since its launch, Pardon My French! is a pocket-sized dictionary of French and English slang as it is spoken today. This edition includes even more non-standard language from the colloquial to the vulgar, with over 2,500 terms added. Ideal for both Francophobes and Francophiles alike. Over 14,000 referencesDozens of helpful usage notes to explain interesting meanings and originsThematic panels on the slang of sex, alcohol, violence etcFully updated and revised panels on varieties of slang (eg verlan, javanais, Black American slang)

  20. Python pocket reference, version 2.4

    CERN Document Server

    Lutz, Mark

    2005-01-01

    Python is optimized for quality, productivity, portability, and integration. Hundreds of thousands of Python developers around the world rely on Python for general-purpose tasks, Internet scripting, systems programming, user interfaces, and product customization. Available on all major computing platforms, including commercial versions of Unix, Linux, Windows, and Mac OS X, Python is portable, powerful and remarkable easy to use. With its convenient, quick-reference format, Python Pocket Reference, 3rd Edition is the perfect on-the-job reference. More importantly, it's now been refreshed

  1. Gravitational pocket billiards with MathematicaTM

    OpenAIRE

    Antón, C.; Brun, J.L.

    2009-01-01

    Playing pocket billiards with two gravitational attracting balls and a non-interacting hole requires one to know the trajectories of the balls and therefore to be an "artisan" in the so-called two-body problem, one of the milestones for undergraduate students of Classical Mechanics.Jugar al billar con dos bolas sometidas a interacción gravitatoria y un hoyo no interactuante precisa conocer las trayectorias de las bolas de billar y, además, ser un "artesano" en el bien conocido Problema de Dos...

  2. AIR for Javascript Developers Pocket Guide

    CERN Document Server

    Chambers, Mike; Hoyt, Kevin; Georgita, Dragos

    2009-01-01

    This book is the official guide to Adobe ® AIR[TM], written by members of the AIR team. With Adobe AIR, web developers can use technologies like HTML and JavaScript to build and deploy web applications to the desktop. Packed with examples, this book explains how AIR works and features recipes for performing common runtime tasks. Part of the Adobe Developer Library, this concise pocket guide explains: What Adobe AIR is, and the problems this runtime aims to solveHow to set up your development environmentThe HTML and JavaScript environments within AIRHow to create your first AIR application

  3. Mac OS X Snow Leopard pocket guide

    CERN Document Server

    Seiblod, Chris

    2009-01-01

    Whether you're new to the Mac or a longtime user, this handy book is the quickest way to get up to speed on Snow Leopard. Packed with concise information in an easy-to-read format, Mac OS X Snow Leopard Pocket Guide covers what you need to know and is an ideal resource for problem-solving on the fly. This book goes right to the heart of Snow Leopard, with details on system preferences, built-in applications, and utilities. You'll also find configuration tips, keyboard shortcuts, guides for troubleshooting, lots of step-by-step instructions, and more. Learn about new features and changes s

  4. Pocket guide for improving board performance.

    Science.gov (United States)

    1994-01-01

    This pocket guide, a supplement to "The Family Planning Manager," provides suggestions for building an effective, supportive board of directors. Among the topics covered are defining the board's terms of office, board committees, criteria for selecting board members and the board leader, dealing with key family planning issues, and ethical concerns. Also included is a sample chart for keeping track of board diversity in terms of age, gender, ethnicity, and professional and organizational experience. Yet another section sets forth a sample board member job description, including requirements, functional responsibilities, and expectations. PMID:12291665

  5. E88, a new cyclic-di-GMP class I riboswitch aptamer from Clostridium tetani, has a similar fold to the prototypical class I riboswitch, Vc2, but differentially binds to c-di-GMP analogs.

    Science.gov (United States)

    Luo, Yiling; Chen, Bin; Zhou, Jie; Sintim, Herman O; Dayie, T Kwaku

    2014-03-01

    C-di-GMP has emerged as a ubiquitous second messenger, which regulates the transition between sessile and motile lifestyles and virulence factor expression in many pathogenic bacteria using both RNA riboswitches and protein effectors. We recently showed that two additional class I c-di-GMP riboswitch aptamers (Ct-E88 and Cb-17B) bind c-di-GMP with nanomolar affinity, and that Ct-E88 RNA binds 2'-F-c-di-GMP 422 times less tightly than class I Vc2 RNA. Based on sequence comparison, it was concluded that the global folds of Ct-E88 and Vc2 RNAs were similar and that differences in ligand binding were probably due to differences in binding site architectures. Herein, we utilized EMSA, aptamer sensing spinach modules, SAXS and 1D NMR titration to study the conformational transitions of Ct-E88. We conclude that whereas the global folds of the bound states of Vc2 and Ct-E88 RNAs are similar, the unbound states are different and this could explain differences in ligand affinities between these class I c-di-GMP riboswitches. PMID:24430255

  6. Pairwise structure alignment specifically tuned for surface pockets and interaction interfaces

    KAUST Repository

    Cui, Xuefeng

    2015-09-09

    To detect and evaluate the similarities between the three-dimensional (3D) structures of two molecules, various kinds of methods have been proposed for the pairwise structure alignment problem [6, 9, 7, 11]. The problem plays important roles when studying the function and the evolution of biological molecules. Recently, pairwise structure alignment methods have been extended and applied on surface pocket structures [10, 3, 5] and interaction interface structures [8, 4]. The results show that, even when there are no global similarities discovered between the global sequences and the global structures, biological molecules or complexes could share similar functions because of well conserved pockets and interfaces. Thus, pairwise pocket and interface structure alignments are promising to unveil such shared functions that cannot be discovered by the well-studied global sequence and global structure alignments. State-of-the-art methods for pairwise pocket and interface structure alignments [4, 5] are direct extensions of the classic pairwise protein structure alignment methods, and thus such methods share a few limitations. First, the goal of the classic protein structure alignment methods is to align single-chain protein structures (i.e., a single fragment of residues connected by peptide bonds). However, we observed that pockets and interfaces tend to consist of tens of extremely short backbone fragments (i.e., three or fewer residues connected by peptide bonds). Thus, existing pocket and interface alignment methods based on the protein structure alignment methods still rely on the existence of long-enough backbone fragments, and the fragmentation issue of pockets and interfaces rises the risk of missing the optimal alignments. Moreover, existing interface structure alignment methods focus on protein-protein interfaces, and require a "blackbox preprocessing" before aligning protein-DNA and protein-RNA interfaces. Therefore, we introduce the PROtein STucture Alignment

  7. Modal Similarity

    OpenAIRE

    Vigo , Dr. Ronaldo

    2009-01-01

    Just as Boolean rules define Boolean categories, the Boolean operators define higher-order Boolean categories referred to as modal categories. We examine the similarity order between these categories and the standard category of logical identity (i.e. the modal category defined by the biconditional or equivalence operator). Our goal is 4-fold: first, to introduce a similarity measure for determining this similarity order; second, to show that such a measure is a good predictor of the similari...

  8. Web Similarity

    OpenAIRE

    Cohen, Andrew; Vitányi, Paul

    2015-01-01

    Normalized web distance (NWD) is a similarity or normalized semantic distance based on the World Wide Web or any other large electronic database, for instance Wikipedia, and a search engine that returns reliable aggregate page counts. For sets of search terms the NWD gives a similarity on a scale from 0 (identical) to 1 (completely different). The NWD approximates the similarity according to all (upper semi)computable properties. We develop the theory and give applications. The derivation of ...

  9. Approaches for Identification of HIV-1 Entry Inhibitors Targeting gp41 Pocket

    Directory of Open Access Journals (Sweden)

    Asim K. Debnath

    2013-01-01

    Full Text Available The hydrophobic pocket in the HIV-1 gp41 N-terminal heptad repeat (NHR domain plays an important role in viral fusion and entry into the host cell, and serves as an attractive target for development of HIV-1 fusion/entry inhibitors. The peptide anti-HIV drug targeting gp41 NHR, T-20 (generic name: enfuvirtide; brand name: Fuzeon, was approved by the U.S. FDA in 2003 as the first HIV fusion/entry inhibitor for treatment of HIV/AIDS patients who fail to respond to the current antiretroviral drugs. However, because T20 lacks the pocket-binding domain (PBD, it exhibits low anti-HIV-1 activity and short half-life. Therefore, several next-generation HIV fusion inhibitory peptides with PBD have been developed. They possess longer half-life and more potent antiviral activity against a broad spectrum of HIV-1 strains, including the T-20-resistant variants. Nonetheless, the clinical application of these peptides is still limited by the lack of oral availability and the high cost of production. Thus, development of small molecule compounds targeting the gp41 pocket with oral availability has been promoted. This review describes the main approaches for identification of HIV fusion/entry inhibitors targeting the gp41 pocket and summarizes the latest progress in developing these inhibitors as a new class of anti-HIV drugs.

  10. IsoCleft Finder – a web-based tool for the detection and analysis of protein binding-site geometric and chemical similarities [v2; ref status: indexed, http://f1000r.es/13y

    Directory of Open Access Journals (Sweden)

    Natalja Kurbatova

    2013-05-01

    Full Text Available IsoCleft Finder is a web-based tool for the detection of local geometric and chemical similarities between potential small-molecule binding cavities and a non-redundant dataset of ligand-bound known small-molecule binding-sites. The non-redundant dataset developed as part of this study is composed of 7339 entries representing unique Pfam/PDB-ligand (hetero group code combinations with known levels of cognate ligand similarity. The query cavity can be uploaded by the user or detected automatically by the system using existing PDB entries as well as user-provided structures in PDB format. In all cases, the user can refine the definition of the cavity interactively via a browser-based Jmol 3D molecular visualization interface. Furthermore, users can restrict the search to a subset of the dataset using a cognate-similarity threshold. Local structural similarities are detected using the IsoCleft software and ranked according to two criteria (number of atoms in common and Tanimoto score of local structural similarity and the associated Z-score and p-value measures of statistical significance. The results, including predicted ligands, target proteins, similarity scores, number of atoms in common, etc., are shown in a powerful interactive graphical interface. This interface permits the visualization of target ligands superimposed on the query cavity and additionally provides a table of pairwise ligand topological similarities. Similarities between top scoring ligands serve as an additional tool to judge the quality of the results obtained. We present several examples where IsoCleft Finder provides useful functional information. IsoCleft Finder results are complementary to existing approaches for the prediction of protein function from structure, rational drug design and x-ray crystallography. IsoCleft Finder can be found at: http://bcb.med.usherbrooke.ca/isocleftfinder.

  11. The Influence of Injection Pockets on the Performance of Tilting-Pad Thrust Bearings - Part I: Theory

    DEFF Research Database (Denmark)

    Heinrichson, Niels; Santos, Ilmar; Fuerst, Axel

    2007-01-01

    This is Part I of a two-part series of papers describing the effects of high-pressure injection pockets on the operating conditions of tilting-pad thrust bearings. In Part I a numerical model based on the Reynolds equation is developed extending the threedimensional thermoelastohydrodynamic (TEHD......) analysis of tilting-pad thrust bearings to include the effects of high-pressure injection and recesses in the bearing pads. The model is applied to the analysis of an existing bearing of large dimensions and the influence of the pocket is analyzed. In the analysis, the high-pressure oil injection used for...... hydrostatic jacking is turned off (i.e., only the effect of the pocket is studied). It is shown that a shallow pocket positively influences the performance of the bearing because it has characteristics similar to those of a Rayleigh-step bearing. In Part II of the paper (Heinrichson, N., Fuerst, A., and...

  12. A cation-π interaction at a phenylalanine residue in the glycine receptor binding site is conserved for different agonists

    DEFF Research Database (Denmark)

    Pless, Stephan Alexander; Hanek, Ariele P; Price, Kerry L;

    2011-01-01

    current study, we investigated whether the lower efficacy agonists of the human GlyR β-alanine and taurine also form cation-π interactions with Phe159. By incorporating a series of unnatural amino acids, we found cation-π interactions between Phe159 and the amino groups of β-alanine and taurine. The...... strengths of these interactions were significantly weaker than for glycine. Modeling studies suggest that β-alanine and taurine are orientated subtly differently in the binding pocket, with their amino groups further from Phe159 than that of glycine. These data therefore show that similar agonists can have...... similar but not identical orientations and interactions in the binding pocket and provide a possible explanation for the lower potencies of β-alanine and taurine....

  13. An in silico analysis of the binding modes and binding affinities of small molecule modulators of PDZ-peptide interactions.

    Directory of Open Access Journals (Sweden)

    Garima Tiwari

    Full Text Available Inhibitors of PDZ-peptide interactions have important implications in a variety of biological processes including treatment of cancer and Parkinson's disease. Even though experimental studies have reported characterization of peptidomimetic inhibitors of PDZ-peptide interactions, the binding modes for most of them have not been characterized by structural studies. In this study we have attempted to understand the structural basis of the small molecule-PDZ interactions by in silico analysis of the binding modes and binding affinities of a set of 38 small molecules with known K(i or K(d values for PDZ2 and PDZ3 domains of PSD-95 protein. These two PDZ domains show differential selectivity for these compounds despite having a high degree of sequence similarity and almost identical peptide binding pockets. Optimum binding modes for these ligands for PDZ2 and PDZ3 domains were identified by using a novel combination of semi-flexible docking and explicit solvent molecular dynamics (MD simulations. Analysis of the binding modes revealed most of the peptidomimectic ligands which had high K(i or K(d moved away from the peptide binding pocket, while ligands with high binding affinities remained in the peptide binding pocket. The differential specificities of the PDZ2 and PDZ3 domains primarily arise from differences in the conformation of the loop connecting βB and βC strands, because this loop interacts with the N-terminal chemical moieties of the ligands. We have also computed the MM/PBSA binding free energy values for these 38 compounds with both the PDZ domains from multiple 5 ns MD trajectories on each complex i.e. a total of 228 MD trajectories of 5 ns length each. Interestingly, computational binding free energies show good agreement with experimental binding free energies with a correlation coefficient of approximately 0.6. Thus our study demonstrates that combined use of docking and MD simulations can help in identification of potent inhibitors

  14. INVESTIGATION OF THERMOFORMING TOOL DESIGN AND POCKET QUALITY

    OpenAIRE

    Moustafa, Moustafa

    2015-01-01

    Thermoforming is widely used in manufacturing industries to produce a range of polymer products. The Reflex tape thermoforming system is designed to form flat tape film into pockets. These formed pockets, also called carrier tape, are used in numerous applications to package a large variety of electronic or small mechanical parts. Thermoformed pocket walls are generally not uniform in thickness and often break during the forming process. Uniform wall thickness distribution, especially for dee...

  15. The equilibrium and kinetic drug binding properties of the mouse P-gp1a and P-gp1b P-glycoproteins are similar

    OpenAIRE

    Taylor, J. C.; Ferry, D. R.; Higgins, C F; Callaghan, R

    1999-01-01

    The gene encoding the multidrug resistance P-glycoprotein (P-gp) is duplicated in rodent species and the functional basis for this remains unresolved. Despite a high sequence similarity, the mouse P-gp1a and P-gp1b isoforms show distinct patterns of tissue distribution which suggest a specific role of the P-gp1b isoform in steroid transport. In the present study possible biochemical differences between the isoforms were directly investigated at the level of drug interaction. There was no dete...

  16. CityInMyPocket: Digital Walking Guides

    OpenAIRE

    S. Depuydt; J. Vanattenhoven; Engelen, J.

    2006-01-01

    By the end of this year visitors to the Flemish town of Mechelen can discover the city with the help of the new CityInMyPocket walking guide. Instead of following a person or a book, people can pick up a CityInMyPocket digital walking guide and go sightseeing at their own speed. So, leave your heavy guide books and many flyers at home. CityInMyPocket will tell you just as much, and even more. CityInMyPocket is like having a friend who lives in the neighbourhood showing you around. The goals a...

  17. The use of isomeric testosterone dimers to explore allosteric effects in substrate binding to cytochrome P450 CYP3A4.

    Science.gov (United States)

    Denisov, Ilia G; Mak, Piotr J; Grinkova, Yelena V; Bastien, Dominic; Bérubé, Gervais; Sligar, Stephen G; Kincaid, James R

    2016-05-01

    Cytochrome P450 CYP3A4 is the main drug-metabolizing enzyme in the human liver, being responsible for oxidation of 50% of all pharmaceuticals metabolized by human P450 enzymes. Possessing a large substrate binding pocket, it can simultaneously bind several substrate molecules and often exhibits a complex pattern of drug-drug interactions. In order to better understand structural and functional aspects of binding of multiple substrate molecules to CYP3A4 we used resonance Raman and UV-VIS spectroscopy to document the effects of binding of synthetic testosterone dimers of different configurations, cis-TST2 and trans-TST2. We directly demonstrate that the binding of two steroid molecules, which can assume multiple possible configurations inside the substrate binding pocket of monomeric CYP3A4, can lead to active site structural changes that affect functional properties. Using resonance Raman spectroscopy, we have documented perturbations in the ferric and Fe-CO states by these substrates, and compared these results with effects caused by binding of monomeric TST. While the binding of trans-TST2 yields results similar to those obtained with monomeric TST, the binding of cis-TST2 is much tighter and results in significantly more pronounced conformational changes of the porphyrin side chains and Fe-CO unit. In addition, binding of an additional monomeric TST molecule in the remote allosteric site significantly improves binding affinity and the overall spin shift for CYP3A4 with trans-TST2 dimer bound inside the substrate binding pocket. This result provides the first direct evidence for an allosteric effect of the peripheral binding site at the protein-membrane interface on the functional properties of CYP3A4. PMID:26774838

  18. Oracle PL/SQL Language Pocket Reference

    CERN Document Server

    Feuerstein, Steven; Dawes, Chip

    2004-01-01

    While it's good to have a book with all the answers--like your trusty copy of Oracle PL/SQL Programming-- how often do you need all the answers? More likely, you just need a reminder, a quick answer to a problem you're up against. For these times, nothing's handier than the new edition of the Oracle PL/SQL Language Pocket Reference by PL/SQL experts Stephen Feuerstein, Bill Pribyl, and Chip Dawes. Newly updated for Oracle10g, this little book is always at the ready for the quick problem solving you need. The 3rd edition of this popular mini-reference boils down the most vital information fr

  19. Fpocket: An open source platform for ligand pocket detection

    Directory of Open Access Journals (Sweden)

    Le Guilloux Vincent

    2009-06-01

    Full Text Available Abstract Background Virtual screening methods start to be well established as effective approaches to identify hits, candidates and leads for drug discovery research. Among those, structure based virtual screening (SBVS approaches aim at docking collections of small compounds in the target structure to identify potent compounds. For SBVS, the identification of candidate pockets in protein structures is a key feature, and the recent years have seen increasing interest in developing methods for pocket and cavity detection on protein surfaces. Results Fpocket is an open source pocket detection package based on Voronoi tessellation and alpha spheres built on top of the publicly available package Qhull. The modular source code is organised around a central library of functions, a basis for three main programs: (i Fpocket, to perform pocket identification, (ii Tpocket, to organise pocket detection benchmarking on a set of known protein-ligand complexes, and (iii Dpocket, to collect pocket descriptor values on a set of proteins. Fpocket is written in the C programming language, which makes it a platform well suited for the scientific community willing to develop new scoring functions and extract various pocket descriptors on a large scale level. Fpocket 1.0, relying on a simple scoring function, is able to detect 94% and 92% of the pockets within the best three ranked pockets from the holo and apo proteins respectively, outperforming the standards of the field, while being faster. Conclusion Fpocket provides a rapid, open source and stable basis for further developments related to protein pocket detection, efficient pocket descriptor extraction, or drugablity prediction purposes. Fpocket is freely available under the GNU GPL license at http://fpocket.sourceforge.net.

  20. Identification of essential cannabinoid-binding domains: structural insights into early dynamic events in receptor activation.

    Science.gov (United States)

    Shim, Joong-Youn; Bertalovitz, Alexander C; Kendall, Debra A

    2011-09-23

    The classical cannabinoid agonist HU210, a structural analog of (-)-Δ(9)-tetrahydrocannabinol, binds to brain cannabinoid (CB1) receptors and activates signal transduction pathways. To date, an exact molecular description of the CB1 receptor is not yet available. Utilizing the minor binding pocket of the CB1 receptor as the primary ligand interaction site, we explored HU210 binding using lipid bilayer molecular dynamics (MD) simulations. Among the potential ligand contact residues, we identified residues Phe-174(2.61), Phe-177(2.64), Leu-193(3.29), and Met-363(6.55) as being critical for HU210 binding by mutational analysis. Using these residues to guide the simulations, we determined essential cannabinoid-binding domains in the CB1 receptor, including the highly sought after hydrophobic pocket important for the binding of the C3 alkyl chain of classical and nonclassical cannabinoids. Analyzing the simulations of the HU210-CB1 receptor complex, the CP55940-CB1 receptor complex, and the (-)-Δ(9)-tetrahydrocannabinol-CB1 receptor complex, we found that the positioning of the C3 alkyl chain and the aromatic stacking between Trp-356(6.48) and Trp-279(5.43) is crucial for the Trp-356(6.48) rotamer change toward receptor activation through the rigid-body movement of H6. The functional data for the mutant receptors demonstrated reductions in potency for G protein activation similar to the reductions seen in ligand binding affinity for HU210. PMID:21795705

  1. Heavy chain binding protein (BiP/GRP78) and endoplasmin are exported from the endoplasmic reticulum in rat exocrine pancreatic cells, similar to protein disulfide-isomerase.

    Science.gov (United States)

    Takemoto, H; Yoshimori, T; Yamamoto, A; Miyata, Y; Yahara, I; Inoue, K; Tashiro, Y

    1992-07-01

    Previously we found that in rat exocrine pancreatic cells, protein disulfide-isomerase (PDI), one of the major resident proteins in the lumen of the endoplasmic reticulum (ER) of many cells, is localized not only in the ER but also in the Golgi apparatus, secretory granules, plasma membranes, and even in the glandular lumens, despite possessing the ER retention signal KDEL (Lys-Asp-Glu-Leu) at the carboxyl terminus. In this report, we examined whether other ER luminal proteins bearing the KDEL signal at their C-termini, such as BiP/GRP78 and endoplasmin/GRP94 are also exported from the ER. We prepared two kinds of affinity-purified polyclonal antibodies; one against a synthetic peptide with 12 amino acids which is identical to the carboxyl terminus of BiP and another against purified endoplasmin. Immunoblot analysis using these two antibodies showed that BiP and endoplasmin exist in both the plasma membrane and the microsomal fractions, similar to the intracellular distribution of PDI in rat exocrine pancreas. The ratios of the amount of the three proteins in the two fractions, however, were variable, suggesting that the KDEL-bearing proteins such as PDI, BiP, and endoplasmin are exported from the ER with different efficiencies. Postembedding protein A-immunogold electron microscopy revealed that endoplasmin was exported from the ER and secreted to the extracellular space. The secretion of PDI in rat pancreatic lobules was inhibited by Brefeldin A (BFA) and by guanidino acid esters (FOY-305), which are known to be the inhibitors of the intracellular transport. Taken together with the previous immunogold electron microscopic analyses by Akagi et al. (1988), it is strongly suggested that in rat exocrine pancreatic cells PDI and the other KDEL-bearing proteins found in the extracellular space were not artificially released by cell damage during incubation but were secreted via the normal secretory pathway. PMID:1318687

  2. 30 CFR 56.19103 - Dumping facilities and loading pockets.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Dumping facilities and loading pockets. 56.19103 Section 56.19103 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... Personnel Hoisting Shafts § 56.19103 Dumping facilities and loading pockets. Dumping facilities and...

  3. 30 CFR 57.19103 - Dumping facilities and loading pockets.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Dumping facilities and loading pockets. 57.19103 Section 57.19103 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... MINES Personnel Hoisting Shafts § 57.19103 Dumping facilities and loading pockets. Dumping...

  4. ADAMTS13, lucky to have a hydrophobic pocket

    OpenAIRE

    Zheng, X. Long

    2015-01-01

    In this issue of Blood, de Groot et al identify a hydrophobic pocket in the Cys-rich domain of ADAMTS13 that appears to interact with the hydrophobic pocket in the central A2 domain of von Willebrand factor (VWF) for its proteolysis.1

  5. Molecularly Responsive Binding through Co-occupation of Binding Space: A Lock-Key Story.

    Science.gov (United States)

    Awino, Joseph K; Hu, Lan; Zhao, Yan

    2016-04-01

    When two guest molecules co-occupy a binding pocket of a water-soluble host, the first guest could be used as a signal molecule to turn on the binding of the second. This type of molecularly responsive binding strongly depends on the size of the two guests and the location of the signal molecule. PMID:27001464

  6. An improved digital pocket dosimeter (digidose)

    International Nuclear Information System (INIS)

    More than 3500 Digital Pocket Dosimeters (DIGIDOSE) are being used in a number of DAE facilities. A new model of the dosimeter with overall improvement in power consumption and circuit performance has been developed. The circuit has been redesigned to operate at 3.3V. A single, higher power, 3V Li battery is used along with a micro power DC-DC converter to get 3.3V needed to power the circuit. The detector, amplifier and discriminator are integrated on a separate PCB and the PCB is housed in a copper box to provide shielding from Electro Magnetic Interference (EMI). The new model has lower power consumption, works on a single Li battery and has an improved immunity from EMI. The energy compensation filters have also been redesigned to provide two types of energy response; ±20% from 300keV to 1.25 MeV and ±30% from 60 keV to 1.25 MeV. The circuit details and the characteristics of the dosimeter are discussed. (author)

  7. Improvement of personal dosimetry - Digital pocket dosemeter

    International Nuclear Information System (INIS)

    Physical dosimetric surveillance of professional groups working with various radiation sources is a regular procedure in Croatia, established almost 40 years ago. Data available point out that the majority of professionals under surveillance are those employed in medical facilities, most of them working with X-ray sources. Depending on the nature of professional activities, personnel occupationally exposed to radiation sources are obliged to wear either film badge, TLD or film+TLD badge. Unfortunately, due to the line of data processing, all standard dosemeters have the same disadvantage i.e. up to 40 days delay in dose reporting, regarding the time of actual exposure. The significance of such a delay raises in cases when radiation dose was received within the short time or when technical failure on the operating unit(s) is suspected. Bearing this in mind, the additional dosimetric monitoring becomes an imperative. Therefore, we decided to introduce a palette of digital pocket dosemeters, meant to be used in different workplaces in the radiation zone, each of them being adjusted to the specificities of a particular workplace

  8. Pocket book of integrals and mathematical formulas

    CERN Document Server

    Tallarida, Ronald J

    2008-01-01

    Convenient Organization of Essential Material so You Can Look up Formulas Fast Containing a careful selection of standard and timely topics, the Pocket Book of Integrals and Mathematical Formulas, Fourth Edition presents many numerical and statistical tables, scores of worked examples, and the most useful mathematical formulas for engineering and scientific applications. This fourth edition of a bestseller provides even more comprehensive coverage with the inclusion of several additional topics, all while maintaining its accessible, clear style and handy size. New to the Fourth Edition           An expanded chapter on series that covers many fascinating properties of the natural numbers that follow from number theory           New applications such as geostationary satellite orbits and drug kinetics           An expanded statistics section that discusses nonlinear regression as well as the normal approximation of the binomial distribution           Revised f...

  9. Analysis of ASTER data for mapping bauxite rich pockets within high altitude lateritic bauxite, Jharkhand, India

    Science.gov (United States)

    Guha, Arindam; Singh, Vivek Kr.; Parveen, Reshma; Kumar, K. Vinod; Jeyaseelan, A. T.; Dhanamjaya Rao, E. N.

    2013-04-01

    Bauxite deposits of Jharkhand in India are resulted from the lateritization process and therefore are often associated with the laterites. In the present study, ASTER (Advanced Space borne Thermal Emission and Reflection Radiometer) image is processed to delineate bauxite rich pockets within the laterites. In this regard, spectral signatures of lateritic bauxite samples are analyzed in the laboratory with reference to the spectral features of gibbsite (main mineral constituent of bauxite) and goethite (main mineral constituent of laterite) in VNIR-SWIR (visible-near infrared and short wave infrared) electromagnetic domain. The analysis of spectral signatures of lateritic bauxite samples helps in understanding the differences in the spectral features of bauxites and laterites. Based on these differences; ASTER data based relative band depth and simple ratio images are derived for spatial mapping of the bauxites developed within the lateritic province. In order to integrate the complementary information of different index image, an index based principal component (IPC) image is derived to incorporate the correlative information of these indices to delineate bauxite rich pockets. The occurrences of bauxite rich pockets derived from density sliced IPC image are further delimited by the topographic controls as it has been observed that the major bauxite occurrences of the area are controlled by slope and altitude. In addition to above, IPC image is draped over the digital elevation model (DEM) to illustrate how bauxite rich pockets are distributed with reference to the topographic variability of the terrain. Bauxite rich pockets delineated in the IPC image are also validated based on the known mine occurrences and existing geological map of the bauxite. It is also conceptually validated based on the spectral similarity of the bauxite pixels delineated in the IPC image with the ASTER convolved laboratory spectra of bauxite samples.

  10. Microbial Diversity Similarities in Periodontal Pockets and Atheromatous Plaques of Cardiovascular Disease Patients

    OpenAIRE

    Serra e Silva Filho, Wagner; Casarin, Renato C. V.; Nicolela Junior, Eduardo L.; Passos, Humberto M.; Antônio W Sallum; Gonçalves, Reginaldo B.

    2014-01-01

    Background and Objective The immune and infectious alterations occurring in periodontitis have been shown to alter the development and severity of cardiovascular disease. One of these relationships is the translocation of oral bacteria to atheroma plaques, thereby promoting plaque development. Thus, the aim of this study was to assess, by 16s cloning and sequencing, the microbial diversity of the subgingival environment and atheroma plaques of patients concomitantly suffering from periodontit...

  11. X-ray structures of checkpoint kinase 2 in complex with inhibitors that target its gatekeeper-dependent hydrophobic pocket

    Energy Technology Data Exchange (ETDEWEB)

    Lountos, George T.; Jobson, Andrew G.; Tropea, Joseph E.; Self, Christopher R.; Zhang, Guangtao; Pommier, Yves; Shoemaker, Robert H.; Waugh, David S. (Provid); (NIH); (SAIC); (NCI)

    2012-09-17

    The serine/threonine checkpoint kinase 2 (Chk2) is an attractive molecular target for the development of small molecule inhibitors to treat cancer. Here, we report the rational design of Chk2 inhibitors that target the gatekeeper-dependent hydrophobic pocket located behind the adenine-binding region of the ATP-binding site. These compounds exhibit IC{sub 50} values in the low nanomolar range and are highly selective for Chk2 over Chk1. X-ray crystallography was used to determine the structures of the inhibitors in complex with the catalytic kinase domain of Chk2 to verify their modes of binding.

  12. Ubiquitin-binding proteins: similar, but different

    DEFF Research Database (Denmark)

    Andersen, Katrine M; Hofmann, Kay; Hartmann-Petersen, Rasmus

    2005-01-01

    ubiquitin conjugation to endoplasmic reticulum degradation), UEV [ubiquitin E2 (ubiquitin-conjugating enzyme) variant] and NZF (nuclear protein localization gene 4 zinc finger) domain-containing proteins appear to have more specialized functions. Here we discuss functional and structural properties of...

  13. Computational Analysis of the Ligand Binding Site of the Extracellular ATP Receptor, DORN1.

    Science.gov (United States)

    Nguyen, Cuong The; Tanaka, Kiwamu; Cao, Yangrong; Cho, Sung-Hwan; Xu, Dong; Stacey, Gary

    2016-01-01

    DORN1 (also known as P2K1) is a plant receptor for extracellular ATP, which belongs to a large gene family of legume-type (L-type) lectin receptor kinases. Extracellular ATP binds to DORN1 with strong affinity through its lectin domain, and the binding triggers a variety of intracellular activities in response to biotic and abiotic stresses. However, information on the tertiary structure of the ligand binding site of DORN1is lacking, which hampers efforts to fully elucidate the mechanism of receptor action. Available data of the crystal structures from more than 50 L-type lectins enable us to perform an in silico study of molecular interaction between DORN1 and ATP. In this study, we employed a computational approach to develop a tertiary structure model of the DORN1 lectin domain. A blind docking analysis demonstrated that ATP binds to a cavity made by four loops (defined as loops A B, C and D) of the DORN1 lectin domain with high affinity. In silico target docking of ATP to the DORN1 binding site predicted interaction with 12 residues, located on the four loops, via hydrogen bonds and hydrophobic interactions. The ATP binding pocket is structurally similar in location to the carbohydrate binding pocket of the canonical L-type lectins. However, four of the residues predicted to interact with ATP are not conserved between DORN1 and the other carbohydrate-binding lectins, suggesting that diversifying selection acting on these key residues may have led to the ATP binding activity of DORN1. The in silico model was validated by in vitro ATP binding assays using the purified extracellular lectin domain of wild-type DORN1, as well as mutated DORN1 lacking key ATP binding residues. PMID:27583834

  14. New pseudodimeric aurones as palm pocket inhibitors of Hepatitis C virus RNA-dependent RNA polymerase.

    Science.gov (United States)

    Meguellati, Amel; Ahmed-Belkacem, Abdelhakim; Nurisso, Alessandra; Yi, Wei; Brillet, Rozenn; Berqouch, Nawel; Chavoutier, Laura; Fortuné, Antoine; Pawlotsky, Jean-Michel; Boumendjel, Ahcène; Peuchmaur, Marine

    2016-06-10

    The NS5B RNA-dependent RNA polymerase (RdRp) is a key enzyme for Hepatitis C Virus (HCV) replication. In addition to the catalytic site, this enzyme is characterized by the presence of at least four allosteric pockets making it an interesting target for development of inhibitors as potential anti-HCV drugs. Based on a previous study showing the potential of the naturally occurring aurones as inhibitors of NS5B, we pursued our efforts to focus on pseudodimeric aurones that have never been investigated so far. Hence, 14 original compounds characterized by the presence of a spacer between the benzofuranone moieties were synthesized and investigated as HCV RdRp inhibitors by means of an in vitro assay. The most active inhibitor, pseudodimeric aurone 4, induced high inhibition activity (IC50 = 1.3 μM). Mutagenic and molecular modeling studies reveal that the binding site for the most active derivatives probably is the palm pocket I instead of the thumb pocket I as for the monomeric derivatives. PMID:27017550

  15. Calibrations of pocket dosemeters using a comparison method

    International Nuclear Information System (INIS)

    This monograph is dedicated mainly to the calibration of pocket dosemeters. Various types of radiation sources used in hospitals and different radiation detectors with emphasis on ionization chambers are briefly presented. Calibration methods based on the use of a reference dosemeter were developed to calibrate all pocket dosemeters existing at the Radiation Physics and Metrology Laboratory. Some of these dosemeters were used in personnel dosimetry at hospitals. Moreover, a study was realized about factors that affect the measurements with pocket dosemeters in the long term, such as discharges due to cosmic radiation. A DBASE IV program was developed to store the information included in the hospital's registry

  16. Assessing the structural conservation of protein pockets to study functional and allosteric sites: implications for drug discovery

    Directory of Open Access Journals (Sweden)

    Daura Xavier

    2010-03-01

    Full Text Available Abstract Background With the classical, active-site oriented drug-development approach reaching its limits, protein ligand-binding sites in general and allosteric sites in particular are increasingly attracting the interest of medicinal chemists in the search for new types of targets and strategies to drug development. Given that allostery represents one of the most common and powerful means to regulate protein function, the traditional drug discovery approach of targeting active sites can be extended by targeting allosteric or regulatory protein pockets that may allow the discovery of not only novel drug-like inhibitors, but activators as well. The wealth of available protein structural data can be exploited to further increase our understanding of allosterism, which in turn may have therapeutic applications. A first step in this direction is to identify and characterize putative effector sites that may be present in already available structural data. Results We performed a large-scale study of protein cavities as potential allosteric and functional sites, by integrating publicly available information on protein sequences, structures and active sites for more than a thousand protein families. By identifying common pockets across different structures of the same protein family we developed a method to measure the pocket's structural conservation. The method was first parameterized using known active sites. We characterized the predicted pockets in terms of sequence and structural conservation, backbone flexibility and electrostatic potential. Although these different measures do not tend to correlate, their combination is useful in selecting functional and regulatory sites, as a detailed analysis of a handful of protein families shows. We finally estimated the numbers of potential allosteric or regulatory pockets that may be present in the data set, finding that pockets with putative functional and effector characteristics are widespread across

  17. Investigation on the gas pockets in a rotodynamic multiphase pump

    Science.gov (United States)

    Zhang, J. Y.; Li, Y. J.; Cai, S. J.; Zhu, H. W.; Zhang, Y. X.

    2016-05-01

    The appearance of gas pockets has an obvious impact on the performance of the rotodynamic multiphase pump. In order to study the formation of gas pockets in the pump and its effects on pump's performance, the unsteady numerical simulation and the visualization experiments were done to investigate gas pockets in a three-stage rotodynamic multiphase pump developed by authors. Meanwhile, the mixture of water and air was selected as the medium. According to the distributions of pressure, gas volume fraction and velocity vector in three compression cells in unsteady flow process, the process of the formation of gas pockets in the pump were analysed generally. The visualization experiments were used to verify the validity of the numerical simulation. The results will be benefit for the hydraulic design of the compression cell of rotodynamic multiphase pump.

  18. Out-of-Pocket Costs Rose Moderately Under Obamacare: Report

    Science.gov (United States)

    ... for higher out-of-pocket expenses. Copayments for brand-name prescription drugs were also higher, on average, in marketplace plans than in employer-based plans, the study revealed. Under marketplace plans, ...

  19. The influence of Injection Pockets on the Performance of Tilting-Pad Thrust Bearings: Part I - Theory

    DEFF Research Database (Denmark)

    Heinrichson, Niels; Santos, Ilmar; Fuerst, Axel

    2006-01-01

    This is Part I of a two-part series of papers describing the effects of high pressure injection pockets on the operating conditions of tilting-pad thrust bearings. A numerical model based on the Reynolds equation is developed extending the three dimensional thermo-elasto-hydrodynamic (TEHD......) analysis of tilting-pad thrust bearings to include the effects of high pressure injection and recesses in the bearing pad. The model is applied to the analysis of an existing bearing of large dimensions and the influence of the pocket is analyzed. It is shown that a shallow pocket positively influences the...... performance of the bearing as it has characteristics similar to those of a parallel step bearing....

  20. Structure of Bacillus subtilis γ-glutamyltranspeptidase in complex with acivicin: diversity of the binding mode of a classical and electrophilic active-site-directed glutamate analogue

    International Nuclear Information System (INIS)

    The binding modes of acivicin, a classical and an electrophilic active-site-directed glutamate analogue, to bacterial γ-glutamyltranspeptidases were found to be diverse. γ-Glutamyltranspeptidase (GGT) is an enzyme that plays a central role in glutathione metabolism, and acivicin is a classical inhibitor of GGT. Here, the structure of acivicin bound to Bacillus subtilis GGT determined by X-ray crystallography to 1.8 Å resolution is presented, in which it binds to the active site in a similar manner to that in Helicobacter pylori GGT, but in a different binding mode to that in Escherichia coli GGT. In B. subtilis GGT, acivicin is bound covalently through its C3 atom with sp2 hybridization to Thr403 Oγ, the catalytic nucleophile of the enzyme. The results show that acivicin-binding sites are common, but the binding manners and orientations of its five-membered dihydroisoxazole ring are diverse in the binding pockets of GGTs

  1. UML 2.0 Pocket Reference UML Syntax and Usage

    CERN Document Server

    Pilone, Dan

    2006-01-01

    Globe-trotting travelers have long resorted to handy, pocket-size dictionaries as an aid to communicating across the language barrier. Dan Pilone's UML 2.0 Pocket Reference is just such an aid for on-the-go developers who need to converse in the Unified Modeling Language (UML). Use this book to decipher the many UML diagrams you'll encounter on the path to delivering a modern software system. Updated to cover the very latest in UML, you'll find coverage of the following UML 2.0 diagram types: Class diagramsComponent diagrams*Sequence diagrams*Communication diagrams*Timing diagrams*Interactio

  2. Microflora cultivable from minocycline strips placed in persisting periodontal pockets

    OpenAIRE

    Leung, WK; Jin, L; Yau, JYY; Q. Sun; Corbet, EF

    2005-01-01

    The microflora that develops on minocycline strips, used as an adjunct in non-surgical periodontal therapy was studied. Minocycline (1.4 mg in polycaprolactone vehicle) and control strips were applied into all residual pockets (PD ≥ 5 mm, ≥2 pockets/subject) of patients with chronic periodontitis 1 month after a course of non-surgical periodontal therapy. Strips were inserted and retained for 3 days, changed to new strips for 3 more days and then removed. Strips were recovered from 14 (eight ...

  3. Apache 2 Pocket Reference For Apache Programmers & Administrators

    CERN Document Server

    Ford, Andrew

    2008-01-01

    Even if you know the Apache web server inside and out, you still need an occasional on-the-job reminder -- especially if you're moving to the newer Apache 2.x. Apache 2 Pocket Reference gives you exactly what you need to get the job done without forcing you to plow through a cumbersome, doorstop-sized reference. This Book provides essential information to help you configure and maintain the server quickly, with brief explanations that get directly to the point. It covers Apache 2.x, giving web masters, web administrators, and programmers a quick and easy reference solution. This pocket r

  4. Why not to ''pocket shoot'': Radiology of intravenous drug abuse

    International Nuclear Information System (INIS)

    Our large population of intravenous drug abusers has increasingly resorted to supraclavicular central venous injection for vascular access. Few reports of complications associated with the practice of supraclavicular ''pocket'' injection have appeared in the radiologic literature. The authors describe the complications associated with this practice, including pneumothorax, mycotic aneurysm, arteriovenous fistula, jugular vein thrombosis, cellulitis, foreign body reaction, and neck abscess. In addition, the authors provide examples of sternoclavicular osteomyelitis. The anatomy of the ''pocket,'' and the pathophysiology and radiographic manifestations of these complications, are reviewed

  5. Pocket radar guide key facts, equations, and data

    CERN Document Server

    Curry, G Richard

    2010-01-01

    ThePocket Radar Guideis a concise collection of key radar facts and important radar data that provides you with necessary radar information when you are away from your office or references. It includes statements and comments on radar design, operation, and performance; equations describing the characteristics and performance of radar systems and their components; and tables with data on radar characteristics and key performance issues.It is intended to supplement other radar information sources by providing a pocket companion to refresh memory and provide details whenever you need them such a

  6. Inhibition of TLR2 signaling by small molecule inhibitors targeting a pocket within the TLR2 TIR domain.

    Science.gov (United States)

    Mistry, Pragnesh; Laird, Michelle H W; Schwarz, Ryan S; Greene, Shannon; Dyson, Tristan; Snyder, Greg A; Xiao, Tsan Sam; Chauhan, Jay; Fletcher, Steven; Toshchakov, Vladimir Y; MacKerell, Alexander D; Vogel, Stefanie N

    2015-04-28

    Toll-like receptor (TLR) signaling is initiated by dimerization of intracellular Toll/IL-1 receptor resistance (TIR) domains. For all TLRs except TLR3, recruitment of the adapter, myeloid differentiation primary response gene 88 (MyD88), to TLR TIR domains results in downstream signaling culminating in proinflammatory cytokine production. Therefore, blocking TLR TIR dimerization may ameliorate TLR2-mediated hyperinflammatory states. The BB loop within the TLR TIR domain is critical for mediating certain protein-protein interactions. Examination of the human TLR2 TIR domain crystal structure revealed a pocket adjacent to the highly conserved P681 and G682 BB loop residues. Using computer-aided drug design (CADD), we sought to identify a small molecule inhibitor(s) that would fit within this pocket and potentially disrupt TLR2 signaling. In silico screening identified 149 compounds and 20 US Food and Drug Administration-approved drugs based on their predicted ability to bind in the BB loop pocket. These compounds were screened in HEK293T-TLR2 transfectants for the ability to inhibit TLR2-mediated IL-8 mRNA. C16H15NO4 (C29) was identified as a potential TLR2 inhibitor. C29, and its derivative, ortho-vanillin (o-vanillin), inhibited TLR2/1 and TLR2/6 signaling induced by synthetic and bacterial TLR2 agonists in human HEK-TLR2 and THP-1 cells, but only TLR2/1 signaling in murine macrophages. C29 failed to inhibit signaling induced by other TLR agonists and TNF-α. Mutagenesis of BB loop pocket residues revealed an indispensable role for TLR2/1, but not TLR2/6, signaling, suggesting divergent roles. Mice treated with o-vanillin exhibited reduced TLR2-induced inflammation. Our data provide proof of principle that targeting the BB loop pocket is an effective approach for identification of TLR2 signaling inhibitors. PMID:25870276

  7. Structural analyses of the Slm1-PH domain demonstrate ligand binding in the non-canonical site.

    Directory of Open Access Journals (Sweden)

    Kanchan Anand

    Full Text Available BACKGROUND: Pleckstrin homology (PH domains are common membrane-targeting modules and their best characterized ligands are a set of important signaling lipids that include phosphatidylinositol phosphates (PtdInsPs. PH domains recognize PtdInsPs through two distinct mechanisms that use different binding pockets on opposite sides of the β-strands 1 and 2: i a canonical binding site delimited by the β1-β2 and β3-β4loops and ii a non-canonical binding site bordered by the β1-β2 and β5-β6loops. The PH domain-containing protein Slm1 from budding yeast Saccharomyces cerevisiae is required for actin cytoskeleton polarization and cell growth. We recently reported that this PH domain binds PtdInsPs and phosphorylated sphingolipids in a cooperative manner. PRINCIPAL FINDINGS: To study the structural basis for the Slm1-PH domain (Slm1-PH specificity, we co-crystallized this domain with different soluble compounds that have structures analogous to anionic lipid head groups of reported Slm1 ligands: inositol 4-phosphate, which mimics phosphatidylinositol-4-phosphate (PtdIns(4P, and phosphoserine as a surrogate for dihydrosphingosine 1-phosphate (DHS1-P. We found electron densities for the ligands within the so-called non-canonical binding site. An additional positively charged surface that contacts a phosphate group was identified next to the canonical binding site. CONCLUSIONS: Our results suggest that Slm1-PH utilizes a non-canonical binding site to bind PtdInsPs, similar to that described for the PH domains of β-spectrin, Tiam1 and ArhGAP9. Additionally, Slm1-PH may have retained an active canonical site. We propose that the presence of both a canonical and a non-canonical binding pocket in Slm1-PH may account for the cooperative binding to PtdInsPs and DHS-1P.

  8. Australian Vocational Education and Training Statistics Pocket Guide, Issued 2011

    Science.gov (United States)

    National Centre for Vocational Education Research (NCVER), 2011

    2011-01-01

    This handy, pocket-sized booklet summarises information from the National Centre for Vocational Education Research's (NCVER's) current statistical publications. It presents statistics about: Australia's public vocational education and training (VET) system (which includes activity undertaken at technical and further education [TAFE] institutes,…

  9. Australian Vocational Education and Training Statistics Pocket Guide, Issued 2012

    Science.gov (United States)

    National Centre for Vocational Education Research (NCVER), 2012

    2012-01-01

    This pocket guide presents statistics about: (1) the public vocational education and training (VET) system, which includes activity undertaken at technical and further education (TAFE) institutes, other government providers, community education providers and publicly funded delivery by private providers; (2) apprentices and trainees, who are…

  10. Out-of-Pocket Costs Rose Moderately Under Obamacare: Report

    Science.gov (United States)

    ... medlineplus/news/fullstory_158832.html Out-of-Pocket Costs Rose Moderately Under Obamacare: Report Enrollees most affected were those who ... than in employer-based plans, the study revealed. Under marketplace plans, ... care visits cost, on average, $29. The average copayment under employer- ...

  11. Simulation of Quantum-Mechanical Measurements with Programmable Pocket Calculators.

    Science.gov (United States)

    Sauer, G.

    1979-01-01

    Described is a method for the illustration of the statistical nature of measurements in quantum physics by means of simulation with pocket calculators. The application to examples like the double-slit experiment, Mott scattering, and the demonstration of the uncertainty relation is discussed. (Author/HM)

  12. Structural Determinants of Binding the Seven-transmembrane Domain of the Glucagon-like Peptide-1 Receptor (GLP-1R).

    Science.gov (United States)

    Yang, Dehua; de Graaf, Chris; Yang, Linlin; Song, Gaojie; Dai, Antao; Cai, Xiaoqing; Feng, Yang; Reedtz-Runge, Steffen; Hanson, Michael A; Yang, Huaiyu; Jiang, Hualiang; Stevens, Raymond C; Wang, Ming-Wei

    2016-06-17

    The glucagon-like peptide-1 receptor (GLP-1R) belongs to the secretin-like (class B) family of G protein-coupled receptors. Members of the class B family are distinguished by their large extracellular domain, which works cooperatively with the canonical seven-transmembrane (7TM) helical domain to signal in response to binding of various peptide hormones. We have combined structure-based site-specific mutational studies with molecular dynamics simulations of a full-length model of GLP-1R bound to multiple peptide ligand variants. Despite the high sequence similarity between GLP-1R and its closest structural homologue, the glucagon receptor (GCGR), nearly half of the 62 stably expressed mutants affected GLP-1R in a different manner than the corresponding mutants in GCGR. The molecular dynamics simulations of wild-type and mutant GLP-1R·ligand complexes provided molecular insights into GLP-1R-specific recognition mechanisms for the N terminus of GLP-1 by residues in the 7TM pocket and explained how glucagon-mimicking GLP-1 mutants restored binding affinity for (GCGR-mimicking) GLP-1R mutants. Structural analysis of the simulations suggested that peptide ligand binding mode variations in the 7TM binding pocket are facilitated by movement of the extracellular domain relative to the 7TM bundle. These differences in binding modes may account for the pharmacological differences between GLP-1 peptide variants. PMID:27059958

  13. Liver fatty acid-binding protein binds monoacylglycerol in vitro and in mouse liver cytosol.

    Science.gov (United States)

    Lagakos, William S; Guan, Xudong; Ho, Shiu-Ying; Sawicki, Luciana Rodriguez; Corsico, Betina; Kodukula, Sarala; Murota, Kaeko; Stark, Ruth E; Storch, Judith

    2013-07-01

    Liver fatty acid-binding protein (LFABP; FABP1) is expressed both in liver and intestinal mucosa. Mice null for LFABP were recently shown to have altered metabolism of not only fatty acids but also monoacylglycerol, the two major products of dietary triacylglycerol hydrolysis (Lagakos, W. S., Gajda, A. M., Agellon, L., Binas, B., Choi, V., Mandap, B., Russnak, T., Zhou, Y. X., and Storch, J. (2011) Am. J. Physiol. Gastrointest. Liver Physiol. 300, G803-G814). Nevertheless, the binding and transport of monoacylglycerol (MG) by LFABP are uncertain, with conflicting reports in the literature as to whether this single chain amphiphile is in fact bound by LFABP. In the present studies, gel filtration chromatography of liver cytosol from LFABP(-/-) mice shows the absence of the low molecular weight peak of radiolabeled monoolein present in the fractions that contain LFABP in cytosol from wild type mice, indicating that LFABP binds sn-2 MG in vivo. Furthermore, solution-state NMR spectroscopy demonstrates two molecules of sn-2 monoolein bound in the LFABP binding pocket in positions similar to those found for oleate binding. Equilibrium binding affinities are ∼2-fold lower for MG compared with fatty acid. Finally, kinetic studies examining the transfer of a fluorescent MG analog show that the rate of transfer of MG is 7-fold faster from LFABP to phospholipid membranes than from membranes to membranes and occurs by an aqueous diffusion mechanism. These results provide strong support for monoacylglycerol as a physiological ligand for LFABP and further suggest that LFABP functions in the efficient intracellular transport of MG. PMID:23658011

  14. Liver Fatty Acid-binding Protein Binds Monoacylglycerol in Vitro and in Mouse Liver Cytosol*

    Science.gov (United States)

    Lagakos, William S.; Guan, Xudong; Ho, Shiu-Ying; Sawicki, Luciana Rodriguez; Corsico, Betina; Kodukula, Sarala; Murota, Kaeko; Stark, Ruth E.; Storch, Judith

    2013-01-01

    Liver fatty acid-binding protein (LFABP; FABP1) is expressed both in liver and intestinal mucosa. Mice null for LFABP were recently shown to have altered metabolism of not only fatty acids but also monoacylglycerol, the two major products of dietary triacylglycerol hydrolysis (Lagakos, W. S., Gajda, A. M., Agellon, L., Binas, B., Choi, V., Mandap, B., Russnak, T., Zhou, Y. X., and Storch, J. (2011) Am. J. Physiol. Gastrointest. Liver Physiol. 300, G803–G814). Nevertheless, the binding and transport of monoacylglycerol (MG) by LFABP are uncertain, with conflicting reports in the literature as to whether this single chain amphiphile is in fact bound by LFABP. In the present studies, gel filtration chromatography of liver cytosol from LFABP−/− mice shows the absence of the low molecular weight peak of radiolabeled monoolein present in the fractions that contain LFABP in cytosol from wild type mice, indicating that LFABP binds sn-2 MG in vivo. Furthermore, solution-state NMR spectroscopy demonstrates two molecules of sn-2 monoolein bound in the LFABP binding pocket in positions similar to those found for oleate binding. Equilibrium binding affinities are ∼2-fold lower for MG compared with fatty acid. Finally, kinetic studies examining the transfer of a fluorescent MG analog show that the rate of transfer of MG is 7-fold faster from LFABP to phospholipid membranes than from membranes to membranes and occurs by an aqueous diffusion mechanism. These results provide strong support for monoacylglycerol as a physiological ligand for LFABP and further suggest that LFABP functions in the efficient intracellular transport of MG. PMID:23658011

  15. Out-Of-Pocket X-Ray, CT Scan Costs Vary Widely

    Science.gov (United States)

    ... fullstory_158853.html Out-of-Pocket X-Ray, CT Scan Costs Vary Widely And trying to get hospitals ... pocket price for a standard chest X-ray, CT scan or ultrasound can vary by hundreds of dollars, ...

  16. Health Promoting Pocket Parks in a Landscape Architectural Perspective

    DEFF Research Database (Denmark)

    Peschardt, Karin Kragsig

    cities have become detached from nature and live most of their daily life indoors where sedentary work and physical inactivity characterise everyday life. It has been suggested that this inactivity has resulted in a rapid increase in a number of lifestyle diseases. Urban green spaces (UGS) have been...... shown to have a positive influence on preventing lifestyle related diseases, although only limited research suggests how the various green spaces in the urban green infrastructure (UGI) can benefit health. Especially knowledge about the role of pocket parks is lacking. The study evaluates the health...... contribute to the health promoting effect. The results from this thesis add knowledge to future evidence based health design processes of health promoting pocket parks....

  17. Pocket PC-based portable gamma-ray spectrometer

    Directory of Open Access Journals (Sweden)

    Kamontip Ploykrachang

    2011-04-01

    Full Text Available A portable gamma-ray spectrometer based on a Pocket PC has been developed. A 12-bit pipeline analog-to-digitalconverter (ADC associated with an implemented pulse height histogram function on field programmable gate array (FPGAoperating at 15 MHz is employed for pulse height analysis from built-in pulse amplifier. The system, which interfaces withthe Pocket PC via an enhanced RS-232 serial port under the microcontroller facilitation, is utilized for spectrum acquisition,display and analysis. The pulse height analysis capability of the system was tested and it was found that the ADC integralnonlinearity of ±0.45% was obtained with the throughput rate at 160 kcps. The overall system performance was tested usinga PIN photodiode-CsI(Tl crystal coupled scintillation detector and gamma standard radioactive sources of Cs-137 andCo-60. Low cost and the compact system size as a result of the implemented logical function are also discussed.

  18. Gas pockets in a wastewater rising main: a case study.

    Science.gov (United States)

    Pozos-Estrada, Oscar; Fuentes-Mariles, Oscar A; Pozos-Estrada, Adrian

    2012-01-01

    This paper presents a case study of an existing wastewater rising main (WWRM) in which an extreme transient event produced by simultaneous power failure of the pumps caused the rupture of a 1.2 m (48 in) prestressed concrete cylinder pipe (PCCP), causing an important leakage of sewage. The event and the methodology followed in order to validate the diagnostics of the failure are described. The detail study included in situ observation of the system, experimental investigation in a setup, hydraulic analysis, as well as details of the structural strength of the WWRM. After the extensive investigation and several simulations of fluid transients for different scenarios and flow conditions, it was found that stationary small gas pockets accumulated at high points of the WWRM were identified as the principal contributory factor of the failure. This case study serves as clear warning of the consequences of operating a WWRM with gas pockets at its high points. PMID:22949261

  19. 24 CFR 570.466 - Additional application submission requirements for Pockets of Poverty-employment opportunities.

    Science.gov (United States)

    2010-04-01

    ... requirements for Pockets of Poverty-employment opportunities. 570.466 Section 570.466 Housing and Urban... application submission requirements for Pockets of Poverty—employment opportunities. Applicants for Action Grants under the Pockets of Poverty provision must describe the number and, to the extent possible,...

  20. Excerpts from THE ROMANCE OF SIAM: A POCKET GUIDE

    OpenAIRE

    Ravine, Jai Arun

    2016-01-01

    These pieces are excerpts from the forthcoming book THE ROMANCE OF SIAM: A POCKET GUIDE, which is a subverted travel guide that interrogates the desire White people have to lose and reinvent themselves in Thailand. I track how this “White love” manifests in the tourism industry, popular American media and the western imaginary in order to reveal the connections between tourism and colonization.

  1. A Mechanism for Pockets of Predictability in Complex Adaptive Systems

    OpenAIRE

    Jorgen Vitting Andersen; Didier Sornette

    2004-01-01

    We document a mechanism operating in complex adaptive systems leading to dynamical pockets of predictability (``prediction days''), in which agents collectively take predetermined courses of action, transiently decoupled from past history. We demonstrate and test it out-of-sample on synthetic minority and majority games as well as on real financial time series. The surprising large frequency of these prediction days implies a collective organization of agents and of their strategies which con...

  2. Newnes circuit calculations pocket book with computer programs

    CERN Document Server

    Davies, Thomas J

    2013-01-01

    Newnes Circuit Calculations Pocket Book: With Computer Programs presents equations, examples, and problems in circuit calculations. The text includes 300 computer programs that help solve the problems presented. The book is comprised of 20 chapters that tackle different aspects of circuit calculation. The coverage of the text includes dc voltage, dc circuits, and network theorems. The book also covers oscillators, phasors, and transformers. The text will be useful to electrical engineers and other professionals whose work involves electronic circuitry.

  3. Pocket computers: a new aid to nutritional support.

    OpenAIRE

    1985-01-01

    A program has been written to run on a pocket computer (Sharp PC-1500) that can be used at the bedside to predict the nutritional requirements of patients with a wide range of clinical conditions. The predictions of the program showed good correlation with measured values for energy and nitrogen requirements. The program was used, with good results, in the management of over 100 patients needing nutritional support. The calculation of nutritional requirements for each patient individually fac...

  4. Design of 50nm Vertical MOSFET Incorporating a Dielectric Pocket

    OpenAIRE

    Donaghy, D; Hall, S.; De Groot, C. H. (Kees); Kunz, V. D.; Ashburn, P.

    2004-01-01

    A new architecture for a vertical MOS transistor is proposed that incorporates a so-calle dielectric pocket (DP) for suppression of short channel effects and bulk punch-through. We outline the advantages that the DP brings and propose a basic fabrication process to realize the device. The design issues of a 50-nm channel device are addressed by numerical simulation. The gate delay of an associated CMOS inverter is assessed in the context of the International Technology Roadmap for Semiconduct...

  5. Substitutions of Thr30 provide mechanistic insight into tryptophan-mediated activation of TRAP binding to RNA

    OpenAIRE

    Payal, Vandana; Gollnick, Paul

    2006-01-01

    TRAP is an 11 subunit RNA binding protein that regulates expression of genes involved in tryptophan biosynthesis and transport in Bacillus subtilis. TRAP is activated to bind RNA by binding up to 11 molecules of l-tryptophan in pockets formed by adjacent subunits. The precise mechanism by which tryptophan binding activates TRAP is not known. Thr30 is in the tryptophan binding pocket. A TRAP mutant in which Thr30 is substituted with Val (T30V) does not bind tryptophan but binds RNA constitutiv...

  6. Film cooling air pocket in a closed loop cooled airfoil

    Science.gov (United States)

    Yu, Yufeng Phillip; Itzel, Gary Michael; Osgood, Sarah Jane; Bagepalli, Radhakrishna; Webbon, Waylon Willard; Burdgick, Steven Sebastian

    2002-01-01

    Turbine stator vane segments have radially inner and outer walls with vanes extending between them. The inner and outer walls are compartmentalized and have impingement plates. Steam flowing into the outer wall plenum passes through the impingement plate for impingement cooling of the outer wall upper surface. The spent impingement steam flows into cavities of the vane having inserts for impingement cooling the walls of the vane. The steam passes into the inner wall and through the impingement plate for impingement cooling of the inner wall surface and for return through return cavities having inserts for impingement cooling of the vane surfaces. To provide for air film cooing of select portions of the airfoil outer surface, at least one air pocket is defined on a wall of at least one of the cavities. Each air pocket is substantially closed with respect to the cooling medium in the cavity and cooling air pumped to the air pocket flows through outlet apertures in the wall of the airfoil to cool the same.

  7. Small organic compounds enhance antigen loading of class II major histocompatibility complex proteins by targeting the polymorphic P1 pocket

    DEFF Research Database (Denmark)

    Höpner, Sabine; Dickhaut, Katharina; Hofstätter, Maria;

    2006-01-01

    the peptide loading rate. The effect was evident only for an allelic subset and strictly correlated with the presence of glycine at the dimorphic position beta86 of the HLA-DR molecule. The residue forms the floor of the conserved pocket P1, located in the peptide binding site of MHC molecule...... "adamantyl-susceptible" MHC molecules. As catalysts of antigen loading, compounds targeting P1 may be useful molecular tools to amplify the immune response. The observation, however, that the ligand repertoire can be affected through polymorphic sites form the outside may also imply that environmental...

  8. Analysis of Pocket Double Gate Tunnel FET for Low Stand by Power Logic Circuits

    Directory of Open Access Journals (Sweden)

    Kamal K. Jha

    2013-12-01

    Full Text Available For low power circuits downscaling of MOSFET has a major issue of scaling of voltage which has ceased after 1V. This paper highlights comparative study and analysis of pocket double gate tunnel FET (DGTFET with MOSFET for low standby power logic circuits. The leakage current of pocket DGTFET and MOSFET have been studied and the analysis results shows that the pocket DGTFET gives the lower leakage current than the MOSFET. Further a pocket DGTFET inverter circuit is design in 32 nm technology node at VDD =0.6 V. The pocket DGTFET inverter shows the significant improvement on the leakage power than multi-threshold CMOS (MTCMOS inverter. The leakage power of pocket DGFET and MTCMOS inverter are 0.116 pW and 1.83 pW respectively. It is found that, the pocket DGTFET can replace the MOSFET for low standby power circuits.

  9. Family 42 carbohydrate-binding modules display multiple arabinoxylan-binding interfaces presenting different ligand affinities.

    Science.gov (United States)

    Ribeiro, Teresa; Santos-Silva, Teresa; Alves, Victor D; Dias, Fernando M V; Luís, Ana S; Prates, José A M; Ferreira, Luís M A; Romão, Maria J; Fontes, Carlos M G A

    2010-10-01

    Enzymes that degrade plant cell wall polysaccharides display a modular architecture comprising a catalytic domain bound to one or more non-catalytic carbohydrate-binding modules (CBMs). CBMs display considerable variation in primary structure and are grouped into 59 sequence-based families organized in the Carbohydrate-Active enZYme (CAZy) database. Here we report the crystal structure of CtCBM42A together with the biochemical characterization of two other members of family 42 CBMs from Clostridium thermocellum. CtCBM42A, CtCBM42B and CtCBM42C bind specifically to the arabinose side-chains of arabinoxylans and arabinan, suggesting that various cellulosomal components are targeted to these regions of the plant cell wall. The structure of CtCBM42A displays a beta-trefoil fold, which comprises 3 sub-domains designated as alpha, beta and gamma. Each one of the three sub-domains presents a putative carbohydrate-binding pocket where an aspartate residue located in a central position dominates ligand recognition. Intriguingly, the gamma sub-domain of CtCBM42A is pivotal for arabinoxylan binding, while the concerted action of beta and gamma sub-domains of CtCBM42B and CtCBM42C is apparently required for ligand sequestration. Thus, this work reveals that the binding mechanism of CBM42 members is in contrast with that of homologous CBM13s where recognition of complex polysaccharides results from the cooperative action of three protein sub-domains presenting similar affinities. PMID:20637315

  10. Theoretical investigation on the diatomic ligand migration process and ligand binding properties in non-O2-binding H-NOX domain.

    Science.gov (United States)

    Zhang, Yuebin; Liu, Li; Wu, Lei; Li, Shuai; Li, Fei; Li, Zhengqiang

    2013-08-01

    The Nostoc sp (Ns) H-NOX (heme-nitric oxide or OXygen-binding) domain shares 35% sequence identity with soluble guanylate cyclase (sGC) and exhibits similar ligand binding property with the sGC. Previously, our molecular dynamic (MD) simulation work identified that there exists a Y-shaped tunnel system hosted in the Ns H-NOX interior, which servers for ligand migration. The tunnels were then confirmed by Winter et al. [PNAS 2011;108(43):E 881-889] recently using x-ray crystallography with xenon pressured conditions. In this work, to further investigate how the protein matrix of Ns H-NOX modulates the ligand migration process and how the distal residue composition affects the ligand binding prosperities, the free energy profiles for nitric oxide (NO), carbon monooxide (CO), and O2 migration are explored using the steered MDs simulation and the ligand binding energies are calculated using QM/MM schemes. The potential of mean force profiles suggest that the longer branch of the tunnel would be the most favorable route for NO migration and a second NO trapping site other than the distal heme pocket along this route in the Ns H-NOX was identified. On the contrary, CO and O2 would prefer to diffuse via the shorter branch of the tunnel. The QM/MM (quantum mechanics/molecular mechanics) calculations suggest that the hydrophobic distal pocket of Ns H-NOX would provide an approximately vacuum environment and the ligand discrimination would be determined by the intrinsic binding properties of the diatomic gas ligand to the heme group. PMID:23504767

  11. Role of Desolvation in Thermodynamics and Kinetics of Ligand Binding to a Kinase

    OpenAIRE

    Mondal, Jagannath; Friesner, Richard A.; Berne, B. J.

    2014-01-01

    Computer simulations are used to determine the free energy landscape for the binding of the anticancer drug Dasatinib to its src kinase receptor and show that before settling into a free energy basin the ligand must surmount a free energy barrier. An analysis based on using both the ligand-pocket separation and the pocket-water occupancy as reaction coordinates shows that the free energy barrier is a result of the free energy cost for almost complete desolvation of the binding pocket. The sim...

  12. Practical Pocket PC Application w/Biometric Security

    Science.gov (United States)

    Logan, Julian

    2004-01-01

    I work in the Flight Software Engineering Branch, where we provide design and development of embedded real-time software applications for flight and supporting ground systems to support the NASA Aeronautics and Space Programs. In addition, this branch evaluates, develops and implements new technologies for embedded real-time systems, and maintains a laboratory for applications of embedded technology. The majority of microchips that are used in modern society have been programmed using embedded technology. These small chips can be found in microwaves, calculators, home security systems, cell phones and more. My assignment this summer entails working with an iPAQ HP 5500 Pocket PC. This top-of-the-line hand-held device is one of the first mobile PC's to introduce biometric security capabilities. Biometric security, in this case a fingerprint authentication system, is on the edge of technology as far as securing information. The benefits of fingerprint authentication are enormous. The most significant of them are that it is extremely difficult to reproduce someone else's fingerprint, and it is equally difficult to lose or forget your own fingerprint as opposed to a password or pin number. One of my goals for this summer is to integrate this technology with another Pocket PC application. The second task for the summer is to develop a simple application that provides an Astronaut EVA (Extravehicular Activity) Log Book capability. The Astronaut EVA Log Book is what an astronaut would use to report the status of field missions, crew physical health, successes, future plans, etc. My goal is to develop a user interface into which these data fields can be entered and stored. The applications that I am developing are created using eMbedded Visual C++ 4.0 with the Pocket PC 2003 Software Development Kit provided by Microsoft.

  13. Porphyromonas gingivalis invades human pocket epithelium in vitro.

    Science.gov (United States)

    Sandros, J; Papapanou, P N; Nannmark, U; Dahlén, G

    1994-01-01

    The present study examined the adhesive and invasive potential of Porphyromonas gingivalis interacting with human pocket epithelium in vitro. Pocket epithelial tissue, obtained during periodontal surgery of patients with advanced periodontal disease, generated a stratified epithelium in culture. P. gingivalis strains W50 and FDC 381 (laboratory strains), OMGS 712, 1439, 1738, 1739 and 1743 (clinical isolates) as well as Escherichia coli strain HB101 (non-adhering control) were tested with respect to epithelial adhesion and invasion. Adhesion was quantitated by scintillation spectrometry after incubation of radiolabeled bacteria with epithelial cells. The invasive ability of P. gingivalis was measured by means of an antibiotic protection assay. The epithelial multilayers were infected with the test and control strains and subsequently incubated with an antibiotic mixture (metronidazole 0.1 mg/ml and gentamicin 0.5 mg/ml). The number of internalized bacteria surviving the antibiotic treatment was assessed after plating lyzed epithelial cells on culture media. All tested P. gingivalis strains adhered to and entered pocket epithelial cells. However, considerable variation in their adhesive and invasive potential was observed. E. coli strain HB101 did not adhere or invade. Transmission electron microscopy revealed that internalization of P. gingivalis was preceded by formation of microvilli and coated pits on the epithelial cell surfaces. Intracellular bacteria were most frequently surrounded by endosomal membranes; however, bacteria devoid of such membranes were also seen. Release of outer membrane vesicles (blebs) by internalized P. gingivalis was observed. These results support and extend previous work from this laboratory which demonstrated invasion of a human oral epithelial cell-line (KB) by P. gingivalis. PMID:8113953

  14. Windows® Group Policy Administrators Pocket Consultant

    CERN Document Server

    Stanek, William

    2009-01-01

    Portable and precise, this pocket-sized guide delivers ready answers for the day-to-day administration of Group Policy. Zero in on core support and maintenance tasks using quick-reference tables, instructions, and lists. You'll get the focused information you need to solve problems and get the job done-whether at your desk or in the field! Get fast facts to: Configure Local GPOs and Active Directory®-based GPOsManage policy preferences and settingsModel policy changes through the consoleMigrate and maintain the SYSVOLDiagnose and troubleshoot replication issuesKnow when to enforce, block,

  15. Cost and sensitivity exercises with a pocket calculator

    International Nuclear Information System (INIS)

    There are a lot of comprehensive programmes and methods to calculate costs and to simulate mining and processing operations. Sometimes they are not available to the whole people. In this paper it is shown how it is possible, with a pocket programmable calculator less than US $ 200 price, to do exercises in order to estimate the magnitude of investment and operation costs and also their ranges for different practical situations. So, geologists and metallurgists could decide either to spend more money or which aspects need more research. Several examples are developed in order to show how to use a type of these small calculators

  16. Windows® Small Business Server 2008 Administrator's Pocket Consultant

    CERN Document Server

    Zacker, Craig

    2009-01-01

    Portable and precise, this pocket-sized guide delivers ready answers for administering Windows Small Business Server 2008. Zero in on core support tasks and tools using quick-reference tables, instructions, and lists. You'll get the focused information you need to solve problems and get the job done-whether at your desk or in the field. Get fast facts to: Plan, install, and configure a small business network Navigate the Windows SBS Console toolCreate and administer user and group accounts Manage automatic updates, disk storage, and shared printersConfigure mail settings and customize inte

  17. Estimation of cosmic ray dose in airplanes with pocket dosimeters

    International Nuclear Information System (INIS)

    For the purpose of dose control of aircrew, many dose measurements have been conducted in airplanes. In IRPA9, we have reported data mainly based on a Na(Tl) scintillation spectrometer. In the present study, however, analyses were done on data of pocket dosimeters (Silicon detectors: Aloka PDM-101 for ionizing components and PDM-303 for neutrons). As the pocket dosimeters are compact and easy to handle, their uses are certainly advantageous to collect numbers of data with small efforts. However, we need to apply proper conversion as indicated values are not real doses. Currently we have suggested that 2.7 times the indicated value of PDM-101 would approximate the total dose (=ionizing components + neutrons), and about 40% of ionizing components' dose would reflect neutron dose in case 'quality factor Q' before ICRP Publication 60 is used. These conversion factors are based on our simultaneous in-flight measurements with various types of detectors. This paper presents numerical data which provide bases of such conversion. Comparisons are also made between measurements and calculations using computer codes CARI-2/4 to check the reliability of the conversion. Furthermore, special attention was paid to neutron dose in airflights. As neutron dose measurements are scarce, accumulation of data is required first. To meet this, uses of pocket dosimeters are preferable. However, as a neutron detector counts incident protons as well as knocked-on protons induced by incident neutrons, the neutron dose will be overestimated unless contribution of incident protons is rightly removed. In this situation, simultaneous in-flight measurements with PDM-303 and PDM-101 have been conducted in many international and domestic flights covering Japan, China, USA, Brazil and European countries. A linear relationship was obtained between indicated values of PDM-303 and the neutron doses calculated following the aforementioned hypotheses, i.e., neutron dose=2.7x(indicated dose of PDM-101)/1.4x

  18. Newnes audio and Hi-Fi engineer's pocket book

    CERN Document Server

    Capel, Vivian

    2013-01-01

    Newnes Audio and Hi-Fi Engineer's Pocket Book, Second Edition provides concise discussion of several audio topics. The book is comprised of 10 chapters that cover different audio equipment. The coverage of the text includes microphones, gramophones, compact discs, and tape recorders. The book also covers high-quality radio, amplifiers, and loudspeakers. The book then reviews the concepts of sound and acoustics, and presents some facts and formulas relevant to audio. The text will be useful to sound engineers and other professionals whose work involves sound systems.

  19. GPR17: Molecular modeling and dynamics studies of the 3-D structure and purinergic ligand binding features in comparison with P2Y receptors

    Directory of Open Access Journals (Sweden)

    Ranghino Graziella

    2008-06-01

    Full Text Available Abstract Background GPR17 is a G-protein-coupled receptor located at intermediate phylogenetic position between two distinct receptor families: the P2Y and CysLT receptors for extracellular nucleotides and cysteinyl-LTs, respectively. We previously showed that GPR17 can indeed respond to both classes of endogenous ligands and to synthetic compounds active at the above receptor families, thus representing the first fully characterized non-peptide "hybrid" GPCR. In a rat brain focal ischemia model, the selective in vivo knock down of GPR17 by anti-sense technology or P2Y/CysLT antagonists reduced progression of ischemic damage, thus highlighting GPR17 as a novel therapeutic target for stroke. Elucidation of the structure of GPR17 and of ligand binding mechanisms are the necessary steps to obtain selective and potent drugs for this new potential target. On this basis, a 3-D molecular model of GPR17 embedded in a solvated phospholipid bilayer and refined by molecular dynamics simulations has been the first aim of this study. To explore the binding mode of the "purinergic" component of the receptor, the endogenous agonist UDP and two P2Y receptor antagonists demonstrated to be active on GPR17 (MRS2179 and cangrelor were then modeled on the receptor. Results Molecular dynamics simulations suggest that GPR17 nucleotide binding pocket is similar to that described for the other P2Y receptors, although only one of the three basic residues that have been typically involved in ligand recognition is conserved (Arg255. The binding pocket is enclosed between the helical bundle and covered at the top by EL2. Driving interactions are H-bonds and salt bridges between the 6.55 and 6.52 residues and the phosphate moieties of the ligands. An "accessory" binding site in a region formed by the EL2, EL3 and the Nt was also found. Conclusion Nucleotide binding to GPR17 occurs on the same receptor regions identified for already known P2Y receptors. Agonist

  20. SambVca 2. A Web Tool for Analyzing Catalytic Pockets with Topographic Steric Maps

    KAUST Repository

    Falivene, Laura

    2016-06-27

    Developing more efficient catalysts remains one of the primary targets of organometallic chemists. To accelerate reaching this goal, effective molecular descriptors and visualization tools can represent a remarkable aid. Here, we present a Web application for analyzing the catalytic pocket of metal complexes using topographic steric maps as a general and unbiased descriptor that is suitable for every class of catalysts. To show the broad applicability of our approach, we first compared the steric map of a series of transition metal complexes presenting popular mono-, di-, and tetracoordinated ligands and three classic zirconocenes. This comparative analysis highlighted similarities and differences between totally unrelated ligands. Then, we focused on a recently developed Fe(II) catalyst that is active in the asymmetric transfer hydrogenation of ketones and imines. Finally, we expand the scope of these tools to rationalize the inversion of enantioselectivity in enzymatic catalysis, achieved by point mutation of three amino acids of mononuclear p-hydroxymandelate synthase.

  1. Comparison of right-handed and left-handed dental students in measurement of periodontal pocket depth

    Directory of Open Access Journals (Sweden)

    Kadkhoda Z

    2011-02-01

    Full Text Available "nBackground and Aims: The precision of periodontal pocket measurements with periodontal probe is related to different factors. Some of these are related to examiner. The purpose of this study was to compare the right-handed and left-handed dental students in the measurement of periodontal pocket depth (PPD."nMaterials and Methods: Eight systemically healthy adult patients (mean age of 35 years with 0.5-6 mm periodontal pocket depth and a minimum of 20 teeth were examined by 4 right-handed and 4 left-handed students of dentistry (mean age of 25 years. These students were trained for periodontal examination probe depth measurements with Williams probe. Measurements were inserted in SPSS software and analyzed with Iintraclass correlation coefficient (ICCS and T-test."nResults: There was statistically significant difference in the measurement of PPD between right-handed and left-handed examiners in the whole mouth (P<0.05, but this difference (0.08 mm was not clinically significant. The most difference was found in the posterior teeth of mandible at right quadrant (mean=0.2 mm. Analyses of each pair of same handed and different handed examiners with T-test and ICCS showed that these measurements were nearly similar and reproducible."nConclusion: There was no clinically significant difference in measurement of PPD between right-handed and left-handed examiners.

  2. Design of electronic pen pocket dosimeter with wireless battery charger

    International Nuclear Information System (INIS)

    this paper presents the design of pen-thin electronic pocket dosimeter with high accuracy to measure personal accumulated quantities of gamma rays and the strength of the radiation field and display them on the integrated alphanumerical liquid crystal display (LCD). to overcome the need of removing the micro controller from the PCB to reprogram it , we use in circuit serial programming (ICSP) method which enhances the flexibility of the pocket dosimeter design as it reduces costs of field upgrades, reduces time to market, allows easy calibration of our system during manufacturing and allows adding a unique identification code (ID) to each instrument. the design of this device is based on the PIC16F876 micro controller and powered from two AAA size, 250 m Ah rechargeable batteries. recharging of these batteries is done using wireless charger which is the new trend now in charging devices. the design of this charger is based on the principle of magnetic inductive power transfer by sending the power through an air gap between a transmitting circuit in the attached docking station and receiving circuit which is built in the instrument

  3. Ligand binding pocket function of drosophila USP is necessary for metamorphosis

    Science.gov (United States)

    The widely accepted paradigm that epoxidized methyl farnesoates (“juvenile hormones,” JHs) are the principle sesquiterpenoid hormones regulating insect metamorphosis was assessed in Drosophila melanogaster. GC-MS analysis showed that methyl farnesoate, rather than methyl epoxyfarnesoate (= JH III), ...

  4. Adjusting the binding thermodynamics, kinetics, and orientation of guests within large synthetic hydrophobic pockets

    OpenAIRE

    Gibb, C. L. D.; Li, X.; Gibb, B C.

    2002-01-01

    Kinetic analysis of the host guest complexation of a large, open molecular basket and a highly complementary adamantoid guest reveals that for these types of systems a dissociative mechanism is in operation. Hence, the resident adamantyl guest must completely vacate the cavity before another guest molecule can move in to replace it. As a result of the rigid nature of the host, the energy barrier to this process is relatively high, about 16 kcal mol−1 at room temperature. ...

  5. Characterization of the metal binding histidine pockets at the surface of mammalian IgGs

    Czech Academy of Sciences Publication Activity Database

    Tishchenko, Galina; Hašek, Jindřich; Strachota, Adam; Skálová, Tereza; Buchtelová, Eva; Kurková, Dana; Brynda, Eduard; Štouračová, Renata

    Compiegne : University of Technology, 2003. s. 49. [International Symposium on Polymer Design for BioSeparation and Nanobiotechnology /8./. 27.11.2003-29.11.2003, Compiegne] R&D Projects: GA AV ČR KSK4055109 Institutional research plan: CEZ:AV0Z5052915; CEZ:AV0Z4050913 Keywords : mammalian immunoglobulin Subject RIV: CC - Organic Chemistry

  6. A Novel Peptide Binding Prediction Approach for HLA-DR Molecule Based on Sequence and Structural Information

    Science.gov (United States)

    Li, Zhao; Zhao, Yilei; Pan, Gaofeng; Tang, Jijun; Guo, Fei

    2016-01-01

    MHC molecule plays a key role in immunology, and the molecule binding reaction with peptide is an important prerequisite for T cell immunity induced. MHC II molecules do not have conserved residues, so they appear as open grooves. As a consequence, this will increase the difficulty in predicting MHC II molecules binding peptides. In this paper, we aim to propose a novel prediction method for MHC II molecules binding peptides. First, we calculate sequence similarity and structural similarity between different MHC II molecules. Then, we reorder pseudosequences according to descending similarity values and use a weight calculation formula to calculate new pocket profiles. Finally, we use three scoring functions to predict binding cores and evaluate the accuracy of prediction to judge performance of each scoring function. In the experiment, we set a parameter α in the weight formula. By changing α value, we can observe different performances of each scoring function. We compare our method with the best function to some popular prediction methods and ultimately find that our method outperforms them in identifying binding cores of HLA-DR molecules. PMID:27340658

  7. Acute phase of healing - laser assisted pocket debridement versus convention hand instrumentation

    OpenAIRE

    Minovska, Ana

    2013-01-01

    Essentially, the no-surgical periodontal treatment is accomplished with pocket debridement which can be carryout either with conventional, mechanical or, since recently, with laser treatment. In periodontal pocket therapy, laser devices can not only ablate the diseased tissues and decontaminate and detoxify the pockets and root surfaces but also can stimulate or activate the surrounding gingival and bone tissues. It has been suggested that the erbium laser wavelengths present the broadest ra...

  8. STUDY OF RELATIONSHIP BETWEEN DEPTH OF PERIODONTAL POCKETS, ANAEROBIC BACTERIA AND INFLAMMATORY CELLS IN PERIODONTITIS

    OpenAIRE

    P. Owlia; Salari MH.; H Saderi; Z. Kadkhoda

    2000-01-01

    In this study 100 cases of advanced periodontitis were compared with a control group of 100 persons. The parameters were the depth of the periodontal pockets, radiographic images, presence of inflammatory cells and different types of anaerobic bacteria in the pockets. The depth of pocket was measured by a sterile probe and the presence of inflammatory cells was determined through sterile curettage. The smears were stained by Gimsa and Gram methods. For the purpose of microbiological studies, ...

  9. Optimal design of Tilting-Pad Thrust Bearings with High Pressure Injection Pockets

    DEFF Research Database (Denmark)

    Heinrichson, Niels; Santos, Ilmar

    2006-01-01

    A thermo-elasto-hydrodynamic(TEHD) model based on the Reynolds equation has been used to study the effect of oil injection pockets on the performance of tilting pad thrust bearings. The optimal position of the pivot both with respect to load carrying capacity and minimal power consumption is seen...... to move towards the leading edge of the pads as the pocket size is increased. A large pocket is seen to negatively influence the performance with respect to friction loss at most operating conditions while at some operating conditions it has a small positive influence. The small pocket has a slight...

  10. Exploitation of pocket gophers and their food caches by grizzly bears

    Science.gov (United States)

    Mattson, D.J.

    2004-01-01

    I investigated the exploitation of pocket gophers (Thomomys talpoides) by grizzly bears (Ursus arctos horribilis) in the Yellowstone region of the United States with the use of data collected during a study of radiomarked bears in 1977-1992. My analysis focused on the importance of pocket gophers as a source of energy and nutrients, effects of weather and site features, and importance of pocket gophers to grizzly bears in the western contiguous United States prior to historical extirpations. Pocket gophers and their food caches were infrequent in grizzly bear feces, although foraging for pocket gophers accounted for about 20-25% of all grizzly bear feeding activity during April and May. Compared with roots individually excavated by bears, pocket gopher food caches were less digestible but more easily dug out. Exploitation of gopher food caches by grizzly bears was highly sensitive to site and weather conditions and peaked during and shortly after snowmelt. This peak coincided with maximum success by bears in finding pocket gopher food caches. Exploitation was most frequent and extensive on gently sloping nonforested sites with abundant spring beauty (Claytonia lanceolata) and yampah (Perdieridia gairdneri). Pocket gophers are rare in forests, and spring beauty and yampah roots are known to be important foods of both grizzly bears and burrowing rodents. Although grizzly bears commonly exploit pocket gophers only in the Yellowstone region, this behavior was probably widespread in mountainous areas of the western contiguous United States prior to extirpations of grizzly bears within the last 150 years.

  11. Burden of out-of-pocket expenditure for road traffic injuries in urban India

    Directory of Open Access Journals (Sweden)

    Kumar G

    2012-08-01

    Full Text Available Abstract Background Road traffic injuries (RTI are an increasing public health problem in India where out-of-pocket (OOP expenditures on health are among the highest in the world. We estimated the OOP expenses for RTI in a large city in India. Methods Information on medical and non-medical expenditure was documented for RTI cases of all ages that reported alive or dead to the emergency departments of two public hospitals and a large private hospital in Hyderabad. Differential risk of catastrophic OOP total expenditure (COPE-T and medical expenditure (COPE-M, and distress financing was assessed for 723 RTI cases that arrived alive at the study hospitals with multiple logistic regression. Catastrophic expenditure was defined as expenditure > 25% of the RTI patient’s annual household income. Variation in intensity of COPE-M in RTI was assessed using multiple classification analysis (MCA. Results The median OOP medical and non-medical expenditure was USD 169 and USD 163, respectively. The prevalence of COPE-M and COPE-T was 21.9% (95% CI 18.8-24.9 and 46% (95% CI 42–49.3, respectively. Only 22% had access to medical insurance. Being admitted to a private hospital (OR 5.2, 95% CI 2.7–9.9 and not having access to insurance (OR 3.8, 95% CI 1.9–7.6 were significantly associated with risk of having COPE – M. Similar results were seen for COPE - T. MCA analysis showed that the burden of OOP medical expenditure was mainly associated with in-patient days in hospital (Eta =0.191. Prevalence of distress financing was 69% (95% CI 65.5-72.3 with it being significantly higher for those reporting to the public hospitals (OR 2.8, 95% CI 1.7-4.6, those belonging to the lowest per capita annual household income quartile (OR 7.0, 95% CI 3.7-13.3, and for those without insurance access (OR 3.4, 95% CI 2.0-5.7. Conclusions This paper has outlined the high burden of out-of-pocket medical and total expenditure associated with RTI in India. These data

  12. Relating the shape of protein binding sites to binding affinity profiles: is there an association?

    Directory of Open Access Journals (Sweden)

    Bitter István

    2010-10-01

    Full Text Available Abstract Background Various pattern-based methods exist that use in vitro or in silico affinity profiles for classification and functional examination of proteins. Nevertheless, the connection between the protein affinity profiles and the structural characteristics of the binding sites is still unclear. Our aim was to investigate the association between virtual drug screening results (calculated binding free energy values and the geometry of protein binding sites. Molecular Affinity Fingerprints (MAFs were determined for 154 proteins based on their molecular docking energy results for 1,255 FDA-approved drugs. Protein binding site geometries were characterized by 420 PocketPicker descriptors. The basic underlying component structure of MAFs and binding site geometries, respectively, were examined by principal component analysis; association between principal components extracted from these two sets of variables was then investigated by canonical correlation and redundancy analyses. Results PCA analysis of the MAF variables provided 30 factors which explained 71.4% of the total variance of the energy values while 13 factors were obtained from the PocketPicker descriptors which cumulatively explained 94.1% of the total variance. Canonical correlation analysis resulted in 3 statistically significant canonical factor pairs with correlation values of 0.87, 0.84 and 0.77, respectively. Redundancy analysis indicated that PocketPicker descriptor factors explain 6.9% of the variance of the MAF factor set while MAF factors explain 15.9% of the total variance of PocketPicker descriptor factors. Based on the salient structures of the factor pairs, we identified a clear-cut association between the shape and bulkiness of the drug molecules and the protein binding site descriptors. Conclusions This is the first study to investigate complex multivariate associations between affinity profiles and the geometric properties of protein binding sites. We found that

  13. Development of a pocket multi-channel analyzer

    International Nuclear Information System (INIS)

    A pocket Multi-Channel Analyzer, which is based on 20 pin SMT micro-controller, Serial Peripheral Interfaced ADC and FRAM, and MCU on chip timer/counter acting as de-dead-time clock, was developed and introduced in this paper. Pulse peak hold circuit, MCA timing, micro-controller application techniques, and a reliable simple schematic for peak detection was described as well. The protocol MCA is housed in 110 60 23 mm3. The analyzing resolution can be up to 16384 channels. The dead time is 17 μs when the resolution is programmed to be 1024 channels. It is powered from a single +5V supply, and the power consumption is 360 mW. It can be well embedded in various portable multi-channel spectrum equipments. (authors)

  14. MARTINDALE'S DRUGS RESTRICTED IN SPORT POCKET COMPANION 2009

    Directory of Open Access Journals (Sweden)

    Sean C. Sweetman

    2009-06-01

    Full Text Available Over 500 drugs restricted in sport presented in alphabetical order. To inform and alert the athlete about the potential problem of drug taking for any kind of reasons on and off during training and competition.A comprehensive index of drug names, synonyms, medical usage, single and multi-ingredient preparations and trade (on occasion street names of drugs from 40 countries worldwide (Martindale data. The classification of World Anti-Doping Agency (WADA is added to the explanation of drugs limitation in sport in and out of competition. A glossary of common medical terms is also included.This pocket publication is a must-have list of restricted drugs for athletes, trainers, sports medicine professionals, in short for anyone in exercise physiology and human performance fields.

  15. Pocket book of environmental engineering; Taschenbuch der Umwelttechnik

    Energy Technology Data Exchange (ETDEWEB)

    Schwister, K. (ed.) [Fachhochschule Duesseldorf (Germany)

    2003-07-01

    The pocket book of environmental engineering presents compact, practical, and easy-to-understand information on the complex mechanisms of environmental protection and environmental engineering. The interdependences between soil, water and air are outlined, and measures in the fields of soil and water protection, air pollution abatement, waste volume reduction, noise protection, energy conservation and renewable energy sources are listed. The fundamentals of environmental management are gone into, and current problems like ozone depletion, forest die-back and global climate change are discussed. [German] Das Taschenbuch der Umwelttechnik enthaelt eine kompakte, verstaendliche und an den Beduerfnissen der Praxis ausgerichtete Gesamtdarstellung des Umweltschutzes sowie der Umwelttechnik. Es zeigt die vernetzten stofflichen Zusammenhaenge zwischen den Umweltmedien Boden - Wasser - Luft und stellt die notwendigen Massnahmen in den Bereichen Boden- und Wasserschutz, Luftreinhaltung, Abfallreduzierung, Laermschutz, Energieeinsparung sowie Umstellung auf regenerative Energietraeger uebersichtlich zusammen. Neben den Grundlagen des Umweltmanagements werden konkrete Umweltfragen, z.B. Ozonloch, Waldsterben und Klimawandel, beispielhaft besprochen. (orig.)

  16. Pocket data mining big data on small devices

    CERN Document Server

    Gaber, Mohamed Medhat; Gomes, Joao Bartolo

    2014-01-01

    Owing to continuous advances in the computational power of handheld devices like smartphones and tablet computers, it has become possible to perform Big Data operations including modern data mining processes onboard these small devices. A decade of research has proved the feasibility of what has been termed as Mobile Data Mining, with a focus on one mobile device running data mining processes. However, it is not before 2010 until the authors of this book initiated the Pocket Data Mining (PDM) project exploiting the seamless communication among handheld devices performing data analysis tasks that were infeasible until recently. PDM is the process of collaboratively extracting knowledge from distributed data streams in a mobile computing environment. This book provides the reader with an in-depth treatment on this emerging area of research. Details of techniques used and thorough experimental studies are given. More importantly and exclusive to this book, the authors provide detailed practical guide on the depl...

  17. A pocket warning γ-dosimeter with numerical display

    International Nuclear Information System (INIS)

    A pocket warning dosimeter is described. It provides alarms (continuous tone and a flashing red light) when a presettable dose has been accumulated in the range .064 - 16.4 rads (0.64 - 164 μGy). This warning level can be selected in nine steps of 2 with a switch inside the dosimeter. The dose rate is indicated by a series of sound pulses whose repetition rate is proportional to the dose rate. At 1 rad/h (10 mGy/h) about 17 pluses/minute are emitted. The accumulated dose up to 20 rads (0.2 Gy) is displayed in steps of 1 mrad (10 μGy) with a liquid crystal display. A red LED lights before battery failure occurs. The effects of changes in temperature, battery voltage, dose rate and photon energy upon dosimeter sensitivity are presented. Finally, the applications of the dosimeter are discussed. (auth)

  18. The Six-Inch Lunar Atlas A Pocket Field Guide

    CERN Document Server

    Spain, Don

    2009-01-01

    The Six-Inch Lunar Atlas has been designed specifically for use in the field by lunar observers so it’s perfect for fitting into an observer’s pocket! The author’s own lunar photographs were taken with a 6-inch (150mm) telescope and CCD camera, and closely match the visual appearance of the Moon when viewed through 3-inch to 8-inch telescopes. Each picture is shown oriented "as the Moon really is" when viewed from the northern hemisphere, and is supplemented by exquisite computer sketches that list the main features. Two separate computer sketches are provided to go with each photograph, one oriented to appear as seen through an SCT telescope (e.g. the Meade and Celestron ranges), the other oriented for Newtonian and refracting telescopes. Observers using the various types telescopes will find it extremely helpful to identify lunar features as the human brain is very poor at making "mirror-image" visual translations.

  19. Stabilization of a protein nanocage through the plugging of a protein-protein interfacial water pocket.

    Science.gov (United States)

    Ardejani, Maziar S; Li, Noel X; Orner, Brendan P

    2011-05-17

    The unique structural properties of the ferritin protein cages have provided impetus to focus on the methodical study of these self-assembling nanosystems. Among these proteins, Escherichia coli bacterioferritin (EcBfr), although architecturally very similar to other members of the family, shows structural instability and an incomplete self-assembly behavior by populating two oligomerization states. Through computational analysis and comparison to its homologues, we have found that this protein has a smaller than average dimeric interface on its 2-fold symmetry axis mainly because of the existence of an interfacial water pocket centered around two water-bridged asparagine residues. To investigate the possibility of engineering EcBfr for modified structural stability, we have used a semiempirical computational method to virtually explore the energy differences of the 480 possible mutants at the dimeric interface relative to that of wild-type EcBfr. This computational study also converged on the water-bridged asparagines. Replacing these two asparagines with hydrophobic amino acids resulted in proteins that folded into α-helical monomers and assembled into cages as evidenced by circular dichroism and transmission electron microscopy. Both thermal and chemical denaturation confirmed that, in all cases, these proteins, in agreement with the calculations, possessed increased stability. One of the three mutations shifts the population in favor of the higher-order oligomerization state in solution as evidenced by both size exclusion chromatography and native gel electrophoresis. These results taken together suggest that our low-level design was successful and that it may be possible to apply the strategy of targeting water pockets at protein--protein interfaces to other protein cage and self-assembling systems. More generally, this study further demonstrates the power of jointly employing in silico and in vitro techniques to understand and enhance biostructural

  20. Pocket pathologist: A mobile application for rapid diagnostic surgical pathology consultation

    Directory of Open Access Journals (Sweden)

    Douglas J Hartman

    2014-01-01

    Full Text Available Introduction: Telepathology allows the digital transmission of images for rapid access to pathology experts. Recent technologic advances in smartphones have allowed them to be used to acquire and transmit digital images of the glass slide, representing cost savings and efficiency gains over traditional forms of telepathology. We report our experience with developing an iPhone application (App - Pocket Pathologist to facilitate rapid diagnostic pathology teleconsultation utilizing a smartphone. Materials and Methods: A secure, web-based portal (http://pathconsult.upmc.com/ was created to facilitate remote transmission of digital images for teleconsultation. The App augments functionality of the web-based portal and allows the user to quickly and easily upload digital images for teleconsultation. Image quality of smartphone cameras was evaluated by capturing images using different adapters that directly attach phones to a microscope ocular lens. Results: The App was launched in August 2013. The App facilitated easy submission of cases for teleconsultation by limiting the number of data entry fields for users and enabling uploading of images from their smartphone′s gallery wirelessly. Smartphone cameras properly attached to a microscope create static digital images of similar quality to a commercial digital microscope camera. Conclusion: Smartphones have great potential to support telepathology because they are portable, provide ubiquitous internet connectivity, contain excellent digital cameras, and can be easily attached to a microscope. The Pocket Pathologist App represents a significant reduction in the cost of creating digital images and submitting them for teleconsultation. The iPhone App provides an easy solution for global users to submit digital pathology images to pathology experts for consultation.

  1. Reduction potential and heme-pocket polarity in low potential cytochrome b5 of Giardia intestinalis.

    Science.gov (United States)

    Yang, Zhen Alice; Pazdzior, Robert; Yee, Janet; Rafferty, Steven

    2016-05-01

    Although it lacks mitochondria and the ability to synthesize heme, the protozoan parasite Giardia intestinalis encodes several heme proteins. This includes four members of the cytochrome b5 family, three of which are of similar size to mammalian cytochromes b5 but with reduction potentials that are 140 to 180mV lower. While no structures have yet been determined for any of these proteins, homology modeling points to an increase in heme pocket polarity as a reason for their low potentials. To test this we measured the reduction potentials of four mutants of Giardia cytochrome b5 isotype-I (gCYTB5-I) in which polar residues at two candidate positions (C84, Y51) in the heme pocket were changed to nonpolar ones (C84A, C84F; Y51L, Y51F). All mutants were expressed with comparable levels of heme incorporation and had UV-visible spectra consistent with low spin bis-histidyl coordination. These mutations increased the reduction potential by 18 to 57mV and highlight the influence of C84, which is a residue unique to gCYTB5-I and whose mutation to alanine caused the largest increase. The influence of these two residues plus that of Y61 reported previously accounts for much of the reduction potential difference between gCYTB5-I and microsomal cytochrome b5. A complementary triple mutant of the latter with the hydrophilic residues found in gCYTB5-I bound heme less effectively but nonetheless had a reduction potential that was 135mV lower than wild type. PMID:27048807

  2. Structural analysis of the receptor binding domain of botulinum neurotoxin serotype D

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yanfeng; Buchko, Garry W.; Qin, Lin; Robinson, Howard; Varnum, Susan M.

    2010-10-28

    Botulinum neurotoxins (BoNTs) are the most toxic proteins known. The mechanism for entry into neuronal cells for serotypes A, B, E, F, and G involves a well understood dual receptor (protein and ganglioside) process, however, the mechanism of entry for serotypes C and D remains unclear. To provide structural insights into how BoNT/D enters neuronal cells, the crystal structure of the receptor binding domain (S863-E1276) for this serotype (BoNT/D-HCR) was determined at 1.65 Å resolution. While BoNT/D-HCR adopts an overall fold similar to that observed in other known BoNT HCRs, several major structural differences are present. These structural differences are located at, or near, putative receptor binding sites and may be responsible for BoNT/D host preferences. Two loops, S1195-I1204 and K1236-N1244, located on both sides of the putative protein receptor binding pocket, are displaced >10 Å relative to the corresponding residues in the crystal structures of BoNT/B and G. Obvious clashes were observed in the putative protein receptor binding site when the BoNT/B protein receptor synaptotagmin II was modeled into the BoNT/D-HCR structure. Although a ganglioside binding site has never been unambiguously identified in BoNT/D-HCR, a shallow cavity in an analogous location to the other BoNT serotypes HCR domains is observed in BoNT/D-HCR that has features compatible with membrane binding. A portion of a loop near the putative receptor binding site, K1236-N1244, is hydrophobic and solvent-exposed and may directly bind membrane lipids. Liposome-binding experiments with BoNT/D-HCR demonstrate that this membrane lipid may be phosphatidylethanolamine.

  3. Structural Analysis of the Receptor Binding Domain of Botulinum Neurotoxin Serotype D

    Energy Technology Data Exchange (ETDEWEB)

    Y Zhang; G Buchko; L Qin; H Robinson; S Varnum

    2011-12-31

    Botulinum neurotoxins (BoNTs) are the most toxic proteins known. The mechanism for entry into neuronal cells for serotypes A, B, E, F, and G involves a well understood dual receptor (protein and ganglioside) process, however, the mechanism of entry for serotypes C and D remains unclear. To provide structural insights into how BoNT/D enters neuronal cells, the crystal structure of the receptor binding domain (S863-E1276) for this serotype (BoNT/D-HCR) was determined at 1.65{angstrom} resolution. While BoNT/D-HCR adopts an overall fold similar to that observed in other known BoNT HCRs, several major structural differences are present. These structural differences are located at, or near, putative receptor binding sites and may be responsible for BoNT/D host preferences. Two loops, S1195-I1204 and K1236-N1244, located on both sides of the putative protein receptor binding pocket, are displaced >10{angstrom} relative to the corresponding residues in the crystal structures of BoNT/B and G. Obvious clashes were observed in the putative protein receptor binding site when the BoNT/B protein receptor synaptotagmin II was modeled into the BoNT/D-HCR structure. Although a ganglioside binding site has never been unambiguously identified in BoNT/D-HCR, a shallow cavity in an analogous location to the other BoNT serotypes HCR domains is observed in BoNT/D-HCR that has features compatible with membrane binding. A portion of a loop near the putative receptor binding site, K1236-N1244, is hydrophobic and solvent-exposed and may directly bind membrane lipids. Liposome-binding experiments with BoNT/D-HCR demonstrate that this membrane lipid may be phosphatidylethanolamine.

  4. Binding of a fluorescence reporter and a ligand to an odorant-binding protein of the yellow fever mosquito, Aedes aegypti

    Science.gov (United States)

    Leal, Gabriel M.; Leal, Walter S.

    2015-01-01

    Odorant-binding proteins (OBPs), also named pheromone-binding proteins when the odorant is a pheromone, are essential for insect olfaction. They solubilize odorants that reach the port of entry of the olfactory system, the pore tubules in antennae and other olfactory appendages. Then, OBPs transport these hydrophobic compounds through an aqueous sensillar lymph to receptors embedded on dendritic membranes of olfactory receptor neurons. Structures of OBPs from mosquito species have shed new light on the mechanism of transport, although there is considerable debate on how they deliver odorant to receptors. An OBP from the southern house mosquito, Culex quinquefasciatus, binds the hydrophobic moiety of a mosquito oviposition pheromone (MOP) on the edge of its binding cavity. Likewise, it has been demonstrated that the orthologous protein from the malaria mosquito binds the insect repellent DEET on a similar edge of its binding pocket. A high school research project was aimed at testing whether the orthologous protein from the yellow fever mosquito, AaegOBP1, binds DEET and other insect repellents, and MOP was used as a positive control. Binding assays using the fluorescence reporter N-phenyl-1-naphtylamine (NPN) were inconclusive. However, titration of NPN fluorescence emission in AaegOBP1 solution with MOP led to unexpected and intriguing results. Quenching was observed in the initial phase of titration, but addition of higher doses of MOP led to a stepwise increase in fluorescence emission coupled with a blue shift, which can be explained at least in part by formation of MOP micelles to house stray NPN molecules. PMID:25671088

  5. O2 and Water Migration Pathways between the Solvent and Heme Pockets of Hemoglobin with Open and Closed Conformations of the Distal HisE7.

    Science.gov (United States)

    Shadrina, Maria S; Peslherbe, Gilles H; English, Ann M

    2015-09-01

    Hemoglobin transports O2 by binding the gas at its four hemes. Hydrogen bonding between the distal histidine (HisE7) and heme-bound O2 significantly increases the affinity of human hemoglobin (HbA) for this ligand. HisE7 is also proposed to regulate the release of O2 to the solvent via a transient E7 channel. To reveal the O2 escape routes controlled by HisE7 and to evaluate its role in gating heme access, we compare simulations of O2 diffusion from the distal heme pockets of the T and R states of HbA performed with HisE7 in its open (protonated) and closed (neutral) conformations. Irrespective of HisE7's conformation, we observe the same four or five escape routes leading directly from the α- or β-distal heme pockets to the solvent. Only 21-53% of O2 escapes occur via these routes, with the remainder escaping through routes that encompass multiple internal cavities in HbA. The conformation of the distal HisE7 controls the escape of O2 from the heme by altering the distal pocket architecture in a pH-dependent manner, not by gating the E7 channel. Removal of the HisE7 side chain in the GlyE7 variant exposes the distal pockets to the solvent, and the percentage of O2 escapes to the solvent directly from the α- or β-distal pockets of the mutant increases to 70-88%. In contrast to O2, the dominant water route from the bulk solvent is gated by HisE7 because protonation and opening of this residue dramatically increase the rate of influx of water into the empty distal heme pockets. The occupancy of the distal heme site by a water molecule, which functions as an additional nonprotein barrier to binding of the ligand to the heme, is also controlled by HisE7. Overall, analysis of gas and water diffusion routes in the subunits of HbA and its GlyE7 variant sheds light on the contribution of distal HisE7 in controlling polar and nonpolar ligand movement between the solvent and the hemes. PMID:26226401

  6. Protein contacts and ligand binding in the inward-facing model of human P-glycoprotein.

    Science.gov (United States)

    Pajeva, Ilza K; Hanl, Markus; Wiese, Michael

    2013-05-01

    The primary aim of this work was to analyze the contacts between residues in the nucleotide binding domains (NBDs) and at the interface between the transmembrane domains (TMDs) and the NBDs in the inward-open homology model of human P-glycoprotein (P-gp). The analysis revealed communication nets through hydrogen bonding in the NBD and at the NBD-TMD interface of each half involving residues from the adenosine triphosphate (ATP) motifs and the coupling helices of the intracellular loops. Similar networks have been identified in P-gp conformations generated by molecular dynamics simulation. Differences have been recorded in the networking between both halves of P-gp. Many of the residue contacts have also been observed in the X-ray crystal structures of other ATP binding cassette (ABC) transporters, which confirms their validity. Next, possible binding pockets involving residues of importance for the TMD-NBD communication were identified. By studying these pockets, binding sites were suggested for rhodamine 123 (R-site) and prazosin (regulatory site) at the NBD-TMD interface that agreed with the experimental data on their location. Additionally, one more R-site in the protein cavity was proposed, in accordance with the available biochemical data. Together with the previously suggested Hoechst 33342 site (H-site), all sites were interpreted with respect to their effects on the protein ATPase activity, in correspondence with the experimental observations. Several residues involved in key contacts in the P-gp NBDs were proposed for further targeted mutagenesis experiments. PMID:23564544

  7. Biogenicity of terrestrial oncoids formed in soil pockets, Cayman Brac, British West Indies

    Science.gov (United States)

    Jones, Brian

    2011-05-01

    Terrestrial oncoids, up to 85 mm long, are common in some of the soil-filled pockets found in the finely crystalline dolostones of the Cayman Formation on Cayman Brac. Each of these coated grains has a nucleus formed of a white, finely crystalline dolostone lithoclast (derived from the Cayman Formation) that is encased by a light brown to tan cortex that is formed largely of micrite and minimicrite, is vaguely laminated, and lacks obvious biogenic structures. The cortex, typically microbiota that includes various reticulate filaments that are typically < 1 μm in diameter, cocci, some large-diameter collapsed and calcified filaments, sporangia-like structures, and locally, exopolysaccharides (EPS). In the subsurface parts of the cortices, however, filaments are very rare and there are only scattered cocci. Evidence derived from the surface microbes indicates that they played an active role in the growth of the cortical laminae by binding material to their surfaces, calcification of the microbes, providing substrates on which calcite was precipitated, and forming cavities in which calcite cement was later precipitated. In stark contrast, it is difficult to ascribe a biotic influence to the formation of the subsurface laminae because of the paucity of preserved microbes. The lack of microbes, however, probably reflects the fact that the formative microbes were destroyed during diagenesis. This example clearly demonstrates that the lack of preserved microbes cannot be taken as an indication that the grains formed as a result of abiogenic processes.

  8. Microbiological characteristics of the contents of periodontal pockets of patients with periodontitis adolescents

    Directory of Open Access Journals (Sweden)

    Morgunova V.M.

    2011-03-01

    Full Text Available In this paper we present a study of the contents of periodontal pocket in patients with a diagnosis of chronic generalized periodontitis mild, moderate and severe. Defined genera and species affiliation of anaerobic bacteria by various methods of diagnosis. We found a decreasing trend in the number of associations of microorganisms in periodontal pockets, as the weighting of the pathological process

  9. Microbiological characteristics of the contents of periodontal pockets of patients with periodontitis adolescents

    OpenAIRE

    Morgunova V.M.

    2011-01-01

    In this paper we present a study of the contents of periodontal pocket in patients with a diagnosis of chronic generalized periodontitis mild, moderate and severe. Defined genera and species affiliation of anaerobic bacteria by various methods of diagnosis. We found a decreasing trend in the number of associations of microorganisms in periodontal pockets, as the weighting of the pathological process

  10. The Role of Electronic Pocket Dictionaries as an English Learning Tool among Chinese Students

    Science.gov (United States)

    Jian, Hua-Li; Sandnes, Frode Eika; Law, Kris M. Y.; Huang, Yo-Ping; Huang, Yueh-Min

    2009-01-01

    This study addressed the role of electronic pocket dictionaries as a language learning tool among university students in Hong Kong and Taiwan. The target groups included engineering and humanities students at both undergraduate and graduate level. Speed of reference was found to be the main motivator for using an electronic pocket dictionary.…

  11. Unusual Siderite-Bearing Dendrites in Melt Pockets of the Elga IIE Iron

    Science.gov (United States)

    Teplyakova, S. N.; Artemov, V. V.; Vasiliev, A. L.

    2012-03-01

    The Elga iron contains melt pockets with dedritic texture not only inside Fe,Ni-metal but also inside silicate inclusions (SI). The unusual siderite-bearing melt pockets inside SIs has never been previously observed in any types of meteorites.

  12. 78 FR 54214 - Endangered and Threatened Wildlife and Plants; Removing Five Subspecies of Mazama Pocket Gopher...

    Science.gov (United States)

    2013-09-03

    ...We, the U.S. Fish and Wildlife Service (Service), remove five subspecies of Mazama pocket gopher (Tacoma, Brush Prairie, Shelton, Olympic, and Cathlamet) from the list of candidates for listing as threatened or endangered species under the Endangered Species Act of 1973, as amended. After review of the best available scientific and commercial information, we find that the Tacoma pocket gopher......

  13. Influence of Lubricant Pocket Geometry upon Lubrication Mechanisms on Tool-Workpiece Interfaces in Metal Forming

    DEFF Research Database (Denmark)

    Shimizu, I; Martins, P.A.F.; Bay, Niels; Andreasen, Jan Lasson; Bech, Jakob I.

    Micro lubricant pockets located on the surface of plastically deforming workpieces are recognized to improve the performance of fluid lubrication in a metal forming processes. This work investigates the joint influence of pocket geometry and process working conditions on micro lubrication mechani...

  14. Textual Spatial Cosine Similarity

    OpenAIRE

    Crocetti, Giancarlo

    2015-01-01

    When dealing with document similarity many methods exist today, like cosine similarity. More complex methods are also available based on the semantic analysis of textual information, which are computationally expensive and rarely used in the real time feeding of content as in enterprise-wide search environments. To address these real-time constraints, we developed a new measure of document similarity called Textual Spatial Cosine Similarity, which is able to detect similitude at the semantic ...

  15. Divergent evolution of vitamin B9 binding underlies Juno-mediated adhesion of mammalian gametes.

    Science.gov (United States)

    Han, Ling; Nishimura, Kaoru; Sadat Al Hosseini, Hamed; Bianchi, Enrica; Wright, Gavin J; Jovine, Luca

    2016-02-01

    The interaction between egg and sperm is the first necessary step of fertilization in all sexually reproducing organisms. A decade-long search for a protein pair mediating this event in mammals culminated in the identification of the glycosylphosphatidylinositol (GPI)-anchored glycoprotein Juno as the egg plasma membrane receptor of sperm Izumo1 [1,2]. The Juno-Izumo1 interaction was shown to be essential for fertilization since mice lacking either gene exhibit sex-specific sterility, making these proteins promising non-hormonal contraceptive targets [1,3]. No structural information is available on how gamete membranes interact at fertilization, and it is unclear how Juno - which was previously named folate receptor (FR) 4, based on sequence similarity considerations - triggers membrane adhesion by binding Izumo1. Here, we report the crystal structure of Juno and find that the overall fold is similar to that of FRα and FRβ but with significant flexibility within the area that corresponds to the rigid ligand-binding site of these bona fide folate receptors. This explains both the inability of Juno to bind vitamin B9/folic acid [1], and why mutations within the flexible region can either abolish or change the species specificity of this interaction. Furthermore, structural similarity between Juno and the cholesterol-binding Niemann-Pick disease type C1 protein (NPC1) suggests how the modified binding surface of Juno may recognize the helical structure of the amino-terminal domain of Izumo1. As Juno appears to be a mammalian innovation, our study indicates that a key evolutionary event in mammalian reproduction originated from the neofunctionalization of the vitamin B9-binding pocket of an ancestral folate receptor molecule. PMID:26859261

  16. Combining docking and comparative molecular similarity indices analysis (COMSIA) to predict estrogen activity and probe molecular mechanisms of estrogen activity for estrogen compounds

    Institute of Scientific and Technical Information of China (English)

    YANG XuShu; WANG XiaoDong; JI Li; LI Rong; SUN Cheng; WANG LianSheng

    2008-01-01

    Estrogen compounds are suspected of disrupting endocrine functions by mimicking natural hormones,and such compounds may pose a serious threat to the health of humans and wildlife. Close attention has been paid to the prediction and molecular mechanisms of estrogen activity for estrogen compounds. In this article, estrogen receptor a subtype (Era) -based comparative molecular similarity indices analysis (COMSIA) was performed on 44 estrogen compounds with structural diversity to find out the structural relationship with the activity and to predict the activity. The model with the significant correlation and the best predictive power (R2 = 0.965, (Q2LOO = 0.599, R2pred = 0.825) was achieved. The COMSIA and docking results revealed the structural features for estrogen activity and key amino acid residues in binding pocket, and provided an insight into the interaction between the ligands and these amino acid residues.

  17. Structural fold, conservation and Fe(II) binding of the intracellular domain of prokaryote FeoB

    Energy Technology Data Exchange (ETDEWEB)

    Hung, Kuo-Wei; Chang, Yi-Wei; Eng, Edward T.; Chen, Jai-Hui; Chen, Yi-Chung; Sun, Yuh-Ju; Hsiao, Chwan-Deng; Dong, Gang; Spasov, Krasimir A.; Unger, Vinzenz M.; Huang, Tai-huang (Yale-MED); (Perutz Lab); (AS); (NTHU-Taiwan)

    2010-09-17

    FeoB is a G-protein coupled membrane protein essential for Fe(II) uptake in prokaryotes. Here, we report the crystal structures of the intracellular domain of FeoB (NFeoB) from Klebsiella pneumoniae (KpNFeoB) and Pyrococcus furiosus (PfNFeoB) with and without bound ligands. In the structures, a canonical G-protein domain (G domain) is followed by a helical bundle domain (S-domain), which despite its lack of sequence similarity between species is structurally conserved. In the nucleotide-free state, the G-domain's two switch regions point away from the binding site. This gives rise to an open binding pocket whose shallowness is likely to be responsible for the low nucleotide-binding affinity. Nucleotide binding induced significant conformational changes in the G5 motif which in the case of GMPPNP binding was accompanied by destabilization of the switch I region. In addition to the structural data, we demonstrate that Fe(II)-induced foot printing cleaves the protein close to a putative Fe(II)-binding site at the tip of switch I, and we identify functionally important regions within the S-domain. Moreover, we show that NFeoB exists as a monomer in solution, and that its two constituent domains can undergo large conformational changes. The data show that the S-domain plays important roles in FeoB function.

  18. Micro-Pocket Fission Detectors (MPFD) For Fuel Assembly Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Troy Unruh; Michael Reichenberger; Phillip Ugorowski

    2013-09-01

    Neutron sensors capable of real-time measurement of thermal flux, fast flux, and temperature in a single miniaturized probe are needed in irradiation tests required to demonstrate the performance of candidate new fuels, and cladding materials. In-core ceramic-based miniature neutron detectors or “Micro-Pocket Fission Detectors” (MPFDs) have been studied at Kansas State University (KSU). The first MPFD prototypes were tested in various neutron fields at the KSU TRIGA research reactor with successful results. Currently, a United States Department of Energy-sponsored joint KSU/Idaho National Laboratory (INL) effort is underway to develop a high-temperature, high-pressure version of the MPFD using radiation-resistant, high temperature materials, which would be capable of withstanding irradiation test conditions in high performance material and test reactors (MTRs). Ultimately, this more compact, more accurate, and longer lifetime flux sensor for critical mock-ups, existing and advanced reactor designs, high performance MTRs, and transient test reactors has the potential to lead to higher accuracy and resolution data from irradiation testing, more detailed core flux measurements and enhanced fuel assembly processing. Prior evaluations by KSU indicate that these sensors could also be used to monitor burn-up of nuclear fuel. If integrated into nuclear fuel assemblies, MPFDs offer several advantages to current spent fuel management systems.

  19. Inertial Pocket Navigation System: Unaided 3D Positioning.

    Science.gov (United States)

    Diaz, Estefania Munoz

    2015-01-01

    Inertial navigation systems use dead-reckoning to estimate the pedestrian's position. There are two types of pedestrian dead-reckoning, the strapdown algorithm and the step-and-heading approach. Unlike the strapdown algorithm, which consists of the double integration of the three orthogonal accelerometer readings, the step-and-heading approach lacks the vertical displacement estimation. We propose the first step-and-heading approach based on unaided inertial data solving 3D positioning. We present a step detector for steps up and down and a novel vertical displacement estimator. Our navigation system uses the sensor introduced in the front pocket of the trousers, a likely location of a smartphone. The proposed algorithms are based on the opening angle of the leg or pitch angle. We analyzed our step detector and compared it with the state-of-the-art, as well as our already proposed step length estimator. Lastly, we assessed our vertical displacement estimator in a real-world scenario. We found that our algorithms outperform the literature step and heading algorithms and solve 3D positioning using unaided inertial data. Additionally, we found that with the pitch angle, five activities are distinguishable: standing, sitting, walking, walking up stairs and walking down stairs. This information complements the pedestrian location and is of interest for applications, such as elderly care. PMID:25897501

  20. Pocket dosimeter with alarm 'REM-Master-S'

    International Nuclear Information System (INIS)

    The pocket dosimeters with alarm presently used in nuclear power stations, laboratories, hospitals and so on are mainly of GM counter type, and have such problems as short service life and large characteristic fluctuation. Fuji Electric developed a new type of the dosimeters with alarm ''REM MASTER-S'', which adopted semiconductor detectors and has such features as the measuring range is wider than conventional type, the service life is long, and the size is small and convenient to carry. It is provided with data transmitting and reading functions by opto-electronic communication method so that the exposure dose of individuals can be efficiently controlled. For the development of this new type of dosimeters, Fuji Electric used its technology and experience accumulated in the manufacture of radiation monitors for years. The specifications are as follows. Type: NRS, sensor: silicon semiconductor detector, type S 104S, kind of radiation: X-ray and gamma-ray from 100 keV to 3 MeV, energy dependence: within +-20% from 100 keV to Co-60 (1.3 MeV), integrated calibration accuracy: within +-10% at 100 mR/h with Cs-137 source, linearity of dosage ratio: within +-15% from 10 mR/h to 10 R/h with Cs-137 source, display: 4-digit digital indicator from 0 to 9999 mR, and so on. The application range is shown. (Kako, I.)

  1. Identification of an allosteric pocket on human hsp70 reveals a mode of inhibition of this therapeutically important protein.

    Science.gov (United States)

    Rodina, Anna; Patel, Pallav D; Kang, Yanlong; Patel, Yogita; Baaklini, Imad; Wong, Michael J H; Taldone, Tony; Yan, Pengrong; Yang, Chenghua; Maharaj, Ronnie; Gozman, Alexander; Patel, Maulik R; Patel, Hardik J; Chirico, William; Erdjument-Bromage, Hediye; Talele, Tanaji T; Young, Jason C; Chiosis, Gabriela

    2013-12-19

    Hsp70s are important cancer chaperones that act upstream of Hsp90 and exhibit independent anti-apoptotic activities. To develop chemical tools for the study of human Hsp70, we developed a homology model that unveils a previously unknown allosteric site located in the nucleotide binding domain of Hsp70. Combining structure-based design and phenotypic testing, we discovered a previously unknown inhibitor of this site, YK5. In cancer cells, this compound is a potent and selective binder of the cytosolic but not the organellar human Hsp70s and has biological activity partly by interfering with the formation of active oncogenic Hsp70/Hsp90/client protein complexes. YK5 is a small molecule inhibitor rationally designed to interact with an allosteric pocket of Hsp70 and represents a previously unknown chemical tool to investigate cellular mechanisms associated with Hsp70. PMID:24239008

  2. Coregulator Control of Androgen Receptor Action by a Novel Nuclear Receptor-Binding Motif

    OpenAIRE

    Jehle, Katja; Cato, Laura; Neeb, Antje; Muhle-Goll, Claudia; Jung, Nicole; Smith, Emmanuel W.; Buzon, Victor; Carbó, Laia R.; Estébanez-Perpiñá, Eva; Schmitz, Katja; Fruk, Ljiljana; Luy, Burkhard; Chen, Yu; Cox, Marc B.; Bräse, Stefan

    2014-01-01

    The androgen receptor (AR) is a ligand-activated transcription factor that is essential for prostate cancer development. It is activated by androgens through its ligand-binding domain (LBD), which consists predominantly of 11 α-helices. Upon ligand binding, the last helix is reorganized to an agonist conformation termed activator function-2 (AF-2) for coactivator binding. Several coactivators bind to the AF-2 pocket through conserved LXXLL or FXXLF sequences to enhance the activity of the rec...

  3. Sonographic assessment of predictors of depth of the corner pocket for ultrasound-guided supraclavicular brachial plexus block

    Directory of Open Access Journals (Sweden)

    Naveen Yadav

    2016-01-01

    Conclusion: Prescanning of supraclavicular region for estimating depth of corner pocket should be done before choosing an appropriate size needle. Furthermore, the needle should not be advanced more than the predicted corner pocket depth.

  4. Approximate similarity search

    OpenAIRE

    Amato, Giuseppe

    2000-01-01

    Similarity searching is fundamental in various application areas. Recently it has attracted much attention in the database community because of the growing need to deal with large volume of data. Consequently, efficiency has become a matter of concern in design. Although much has been done to develop structures able to perform fast similarity search, results are still not satisfactory, and more research is needed. The performance of similarity search for complex features deteriorates and does...

  5. Structure of the RNA-Binding Domain of Telomerase: Implications For RNA Recognition and Binding

    Energy Technology Data Exchange (ETDEWEB)

    Rouda,S.; Skordalakes, E.

    2007-01-01

    Telomerase, a ribonucleoprotein complex, replicates the linear ends of eukaryotic chromosomes, thus taking care of the 'end of replication problem.' TERT contains an essential and universally conserved domain (TRBD) that makes extensive contacts with the RNA (TER) component of the holoenzyme, and this interaction is thought to facilitate TERT/TER assembly and repeat-addition processivity. Here, we present a high-resolution structure of TRBD from Tetrahymena thermophila. The nearly all-helical structure comprises a nucleic acid-binding fold suitable for TER binding. An extended pocket on the surface of the protein, formed by two conserved motifs (CP and T motifs) comprises TRBD's RNA-binding pocket. The width and the chemical nature of this pocket suggest that it binds both single- and double-stranded RNA, possibly stem I, and the template boundary element (TBE). Moreover, the structure provides clues into the role of this domain in TERT/TER stabilization and telomerase repeat-addition processivity.

  6. Clustering by Pattern Similarity

    Institute of Scientific and Technical Information of China (English)

    Hai-xun Wang; Jian Pei

    2008-01-01

    The task of clustering is to identify classes of similar objects among a set of objects. The definition of similarity varies from one clustering model to another. However, in most of these models the concept of similarity is often based on such metrics as Manhattan distance, Euclidean distance or other Lp distances. In other words, similar objects must have close values in at least a set of dimensions. In this paper, we explore a more general type of similarity. Under the pCluster model we proposed, two objects are similar if they exhibit a coherent pattern on a subset of dimensions. The new similarity concept models a wide range of applications. For instance, in DNA microarray analysis, the expression levels of two genes may rise and fall synchronously in response to a set of environmental stimuli. Although the magnitude of their expression levels may not be close, the patterns they exhibit can be very much alike. Discovery of such clusters of genes is essential in revealing significant connections in gene regulatory networks. E-commerce applications, such as collaborative filtering, can also benefit from the new model, because it is able to capture not only the closeness of values of certain leading indicators but also the closeness of (purchasing, browsing, etc.) patterns exhibited by the customers. In addition to the novel similarity model, this paper also introduces an effective and efficient algorithm to detect such clusters, and we perform tests on several real and synthetic data sets to show its performance.

  7. Technical Tip for Proximal Release During Open Carpal Tunnel Release Using a Subcutaneous Pocket.

    Science.gov (United States)

    Nikkhah, Dariush; Sadr, Amir H; Akhavani, Mohammed Ali

    2016-06-01

    Technical steps to avoid incomplete proximal release of the carpal tunnel are described. Local anaesthesia is infiltrated as a subcutaneous bleb over the distal wrist crease and extending 2-3 cm over the forearm fascia. Tumescence of local anaesthesia into the subcutaneous plane helps create a pocket between the forearm fascia and subcutaneous tissues. Intraoperatively a subcutaneous pocket is made above the transverse carpal ligament and antebrachial fascia with blunt dissection. A retractor is placed under the pocket, which facilitates optimal visualization to allow reliable complete proximal release of compression.The authors have found that this technique is reproducible and reliable across their collective experience. PMID:27454649

  8. Structural insights into parasite eIF4E binding specificity for m7G and m2,2,7G mRNA caps.

    Science.gov (United States)

    Liu, Weizhi; Zhao, Rui; McFarland, Craig; Kieft, Jeffrey; Niedzwiecka, Anna; Jankowska-Anyszka, Marzena; Stepinski, Janusz; Darzynkiewicz, Edward; Jones, David N M; Davis, Richard E

    2009-11-01

    The eukaryotic translation initiation factor eIF4E recognizes the mRNA cap, a key step in translation initiation. Here we have characterized eIF4E from the human parasite Schistosoma mansoni. Schistosome mRNAs have either the typical monomethylguanosine (m(7)G) or a trimethylguanosine (m(2,2,7)G) cap derived from spliced leader trans-splicing. Quantitative fluorescence titration analyses demonstrated that schistosome eIF4E has similar binding specificity for both caps. We present the first crystal structure of an eIF4E with similar binding specificity for m(7)G and m(2,2,7)G caps. The eIF4E.m(7)GpppG structure demonstrates that the schistosome protein binds monomethyl cap in a manner similar to that of single specificity eIF4Es and exhibits a structure similar to other known eIF4Es. The structure suggests an alternate orientation of a conserved, key Glu-90 in the cap-binding pocket that may contribute to dual binding specificity and a position for mRNA bound to eIF4E consistent with biochemical data. Comparison of NMR chemical shift perturbations in schistosome eIF4E on binding m(7)GpppG and m(2,2,7)GpppG identified key differences between the two complexes. Isothermal titration calorimetry demonstrated significant thermodynamics differences for the binding process with the two caps (m(7)G versus m(2,2,7)G). Overall the NMR and isothermal titration calorimetry data suggest the importance of intrinsic conformational flexibility in the schistosome eIF4E that enables binding to m(2,2,7)G cap. PMID:19710013

  9. The semantic similarity ensemble

    Directory of Open Access Journals (Sweden)

    Andrea Ballatore

    2013-12-01

    Full Text Available Computational measures of semantic similarity between geographic terms provide valuable support across geographic information retrieval, data mining, and information integration. To date, a wide variety of approaches to geo-semantic similarity have been devised. A judgment of similarity is not intrinsically right or wrong, but obtains a certain degree of cognitive plausibility, depending on how closely it mimics human behavior. Thus selecting the most appropriate measure for a specific task is a significant challenge. To address this issue, we make an analogy between computational similarity measures and soliciting domain expert opinions, which incorporate a subjective set of beliefs, perceptions, hypotheses, and epistemic biases. Following this analogy, we define the semantic similarity ensemble (SSE as a composition of different similarity measures, acting as a panel of experts having to reach a decision on the semantic similarity of a set of geographic terms. The approach is evaluated in comparison to human judgments, and results indicate that an SSE performs better than the average of its parts. Although the best member tends to outperform the ensemble, all ensembles outperform the average performance of each ensemble's member. Hence, in contexts where the best measure is unknown, the ensemble provides a more cognitively plausible approach.

  10. Gender similarities and differences.

    Science.gov (United States)

    Hyde, Janet Shibley

    2014-01-01

    Whether men and women are fundamentally different or similar has been debated for more than a century. This review summarizes major theories designed to explain gender differences: evolutionary theories, cognitive social learning theory, sociocultural theory, and expectancy-value theory. The gender similarities hypothesis raises the possibility of theorizing gender similarities. Statistical methods for the analysis of gender differences and similarities are reviewed, including effect sizes, meta-analysis, taxometric analysis, and equivalence testing. Then, relying mainly on evidence from meta-analyses, gender differences are reviewed in cognitive performance (e.g., math performance), personality and social behaviors (e.g., temperament, emotions, aggression, and leadership), and psychological well-being. The evidence on gender differences in variance is summarized. The final sections explore applications of intersectionality and directions for future research. PMID:23808917

  11. Pocket atlas of sectional anatomy: computed tomography and magnetic resonance imaging. Vol. 3. Spine, extremities, joints

    Energy Technology Data Exchange (ETDEWEB)

    Moeller, T.B.; Reif, E. [Caritas Hospital, Dillingen (Germany). Dept. of Radiology

    2007-07-01

    Magnetic resonance imaging (MRI) of the musculoskeletal system is an established and important component in the diagnosis of diseases of the joints, soft tissues, bones, and bone marrow. We are therefore pleased to collect together images of the joints and the spinal column in a separate volume on the musculoskeletal system. Demonstrating the growing importance of new developments in MRI in recent years, with ever-increasing resolution, many images were acquired with 3-tesla units. We are deeply grateful to the manufacturers, Siemens and Philips, for making this possible. We believe that colored atlases are the ideal medium to represent the highly detailed images achieved nowadays with improved resolution techniques. Volume 3 of the Pocket Atlas of Sectional Anatomay provides a color illustration facing each magnetic resonance image, as in the preceding volumes on the skull, thorax, and abdomen. To ensure the greatest possible precision in details, we still produce these illustrations ourselves. Each is accompanied by a sectional image and an orientation aid. Uniform color schemes ensure optimal clarity, as similar structures, such as arteries, veins, nerves, tendons, etc., are consistently represented in the same color. Individual muscle groups are represented uniformly, but differentiated from other muscle groups, so that classification is possible even when numerous groups of muscles are shown in the same image. Maximal lucidity prevails even in highly detailed representations. This is made possible by the high quality of the production and printing process that are characteristic of Thieme International. (orig.)

  12. Complex home care: Part 2- family annual income, insurance premium, and out-of-pocket expenses.

    Science.gov (United States)

    Piamjariyakul, Ubolrat; Yadrich, Donna Macan; Ross, Vicki M; Smith, Carol E; Clements, Faye; Williams, Arthur R

    2010-01-01

    Annual costs paid by families for intravenous infusion of home parenteral nutrition (HPN) health insurance premiums, deductibles, co-payments for health services, and the wide range of out-of-pocket home health care expenses are significant. The costs of managing complex chronic care at home cannot be completely understood until all out-of-pocket costs have been defined, described, and tabulated. Non-reimbursed and out-of-pocket costs paid by families over years for complex chronic care negatively impact the financial stability of families. National health care reform must take into account the long-term financial burdens of families caring for those with complex home care. Any changes that may increase the out-of-pocket costs or health insurance costs to these families can also have a negative long-term impact on society when greater numbers of patients declare bankruptcy or qualify for medical disability. PMID:21158253

  13. Focused surveys for the Pacific Pocket Mouse in Orange County, California

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — The purpose of this report is to document the results of confirmation trapping surveys for the Pacific Pocket Mouse performed by the San Diego Natural History...

  14. Diagnostic accuracy of pocket-size handheld echocardiographs used by cardiologists in the acute care setting

    OpenAIRE

    Testuz, Ariane Marie; Müller, Hajo; Keller, Pierre-Frédéric; Meyer, Philippe; Stampfli, Tomoe Elianne Lybia; Sekoranja, Lucka; Vuille, Cédric; Burri, Haran Kumar

    2013-01-01

    Pocket-size echographs may be useful for bedside diagnosis in acute cardiac care, but their diagnostic accuracy in this setting has not been well tested. Our aim was to evaluate this tool in patients requiring an urgent echocardiogram.

  15. Surgical management of retraction pockets of the pars tensa with cartilage and perichondrial grafts.

    Science.gov (United States)

    Spielmann, P; Mills, R

    2006-09-01

    Stable, self-cleansing retraction pockets of the pars tensa are common incidental findings and require no treatment. In other cases, recurrent discharge occurs and there may also be associated conductive hearing loss. In a minority of cases, cholesteatoma may develop. This paper presents the results of surgery using a graft composed of cartilage and perichondrium for retraction pockets involving the posterior half of the tympanic membrane, as well as early results using a larger graft designed to manage retraction of the entire tympanic membrane. Data on 51 patients with posterior retraction pockets are presented. Forty-two (82 per cent) patients had no aural discharge one year following surgery and the tympanic membrane was not retracted in 43 (84 per cent). The larger 'Mercedes-Benz' graft was used in four patients and the results obtained suggested that it may prove a successful technique for extensive retraction pockets. PMID:16740207

  16. Out-of-pocket expenditures for pharmaceuticals: Lessons from the Austrian household budget survey

    OpenAIRE

    Sanwald, Alice; Theurl, Engelbert

    2015-01-01

    BACKGROUND: Paying pharmaceuticals out-of-pocket is an important source of financing pharmaceutical consumption. Only limited empirical knowledge is available on the determinants of these expenditures. OBJECTIVES: In this paper we analyze which characteristics of private households influence out-of-pocket pharmaceutical expenditure (OOPPE) in Austria. DESIGN & METHODS: We use cross-sectional information on OOPPE and on household characteristics provided by the Austrian household budget survey...

  17. Structural and Chemical Basis for Glucosamine 6-Phosphate Binding and Activation of the glmS Ribozyme

    Energy Technology Data Exchange (ETDEWEB)

    Cochrane, J.; Lipchock, S; Smith, K; Strobel, S

    2009-01-01

    The glmS ribozyme is the first naturally occurring catalytic RNA that relies on an exogenous, nonnucleotide cofactor for reactivity. From a biochemical perspective, the glmS ribozyme derived from Bacillus anthracis is the best characterized. However, much of the structural work to date has been done on a variant glmS ribozyme, derived from Thermoanaerobacter tengcongensis. Here we present structures of the B. anthracis glmS ribozyme in states before the activating sugar, glucosamine 6-phosphate (GlcN6P), has bound and after the reaction has occurred. These structures show an active site preorganized to bind GlcN6P that retains some affinity for the sugar even after cleavage of the RNA backbone. A structure of an inactive glmS ribozyme with a mutation distal from the ligand-binding pocket highlights a nucleotide critical to the reaction that does not affect GlcN6P binding. Structures of the glmS ribozyme bound to a naturally occurring inhibitor, glucose 6-phosphate (Glc6P), and a nonnatural activating sugar, mannosamine 6-phosphate (MaN6P), reveal a binding mode similar to that of GlcN6P. Kinetic analyses show a pH dependence of ligand binding that is consistent with titration of the cofactor's phosphate group and support a model in which the major determinant of activity is the sugar amine independent of its stereochemical presentation.

  18. NEET Micro-Pocket Fission Detector -- FY 2012 Status Report

    Energy Technology Data Exchange (ETDEWEB)

    Troy Unruh; Joy Rempe; Douglas McGregor; Philip Ugorowski; Michael Reichenberger

    2012-09-01

    A research program has been initiated by the NEET program for developing and testing compact miniature fission chambers capable of simultaneously measuring thermal neutron flux, fast neutron flux and temperature within a single package. When implemented, these sensors will significantly advance flux detection capabilities for irradiation tests in US Materials Test Reactors (MTRs).Ultimately, evaluations may lead to a more compact, more accurate, and longer lifetime flux sensor for critical mock-ups, high performance reactors and commercial nuclear power plants. Deployment of Micro-Pocket Fission Detectors (MPFDs) in US DOE-NE program irradiation tests will address several challenges: Current fission chamber technologies do not offer the ability to measure fast flux, thermal flux and temperature within a single compact probe, MPFDs offer this option. MPFD construction is very different then current fission chamber construction; the use of high temperature materials allow MPFDs to be specifically tailored to survive harsh conditions in typical high performance MTR irradiation tests. New high-fidelity reactor physics codes will need a small, accurate, multipurpose in-core sensor to validate the codes without perturbing the validation experiment; MPFDs fill this requirement. MPFDs can be built with variable sensitivities to survive the lifetime of an experiment or fuel assembly in some MTRs; allowing for more efficient and cost effective power monitoring. The small size of the MPFDs allows multiple sensors to be simultaneously deployed; obtaining data required to visualize the reactor flux and temperature profiles. This report summarizes the research progress for year 1 of this 3 year project. An updated design of the MPFD has been developed, materials and tools to support the new design have been procured, construction methods to support the new design have been initiated at INL’s HTTL and KSU’s SMART Laboratory, plating methods are being updated at KSU, new

  19. NEET Micro-Pocket Fission Detector. Final Project report

    Energy Technology Data Exchange (ETDEWEB)

    Unruh, T.; Rempe, Joy; McGregor, Douglas; Ugorowski, Philip; Reichenberger, Michael; Ito, Takashi; Villard, J.-F.

    2014-09-01

    A collaboration between the Idaho National Laboratory (INL), the Kansas State University (KSU), and the French Alternative Energies and Atomic Energy Commission, Commissariat à l'Énergie Atomique et aux Energies Alternatives, (CEA), is funded by the Nuclear Energy Enabling Technologies (NEET) program to develop and test Micro-Pocket Fission Detectors (MPFDs), which are compact fission chambers capable of simultaneously measuring thermal neutron flux, fast neutron flux and temperature within a single package. When deployed, these sensors will significantly advance flux detection capabilities for irradiation tests in US Material Test Reactors (MTRs). Ultimately, evaluations may lead to a more compact, more accurate, and longer lifetime flux sensor for critical mock-ups, and high performance reactors, allowing several Department of Energy Office of Nuclear Energy (DOE-NE) programs to obtain higher accuracy/higher resolution data from irradiation tests of candidate new fuels and materials. Specifically, deployment of MPFDs will address several challenges faced in irradiations performed at MTRs: Current fission chamber technologies do not offer the ability to measure fast flux, thermal flux and temperature within a single compact probe; MPFDs offer this option. MPFD construction is very different than current fission chamber construction; the use of high temperature materials allow MPFDs to be specifically tailored to survive harsh conditions encountered in-core of high performance MTRs. The higher accuracy, high fidelity data available from the compact MPFD will significantly enhance efforts to validate new high-fidelity reactor physics codes and new multi-scale, multi-physics codes. MPFDs can be built with variable sensitivities to survive the lifetime of an experiment or fuel assembly in some MTRs, allowing for more efficient and cost effective power monitoring. The small size of the MPFDs allows multiple sensors to be deployed, offering the potential to

  20. Periodontal pocket as a potential reservoir of high risk human papilloma virus: A pilot study

    Science.gov (United States)

    Dayakar, Manjunath Mundoor; Shipilova, Anna; Gupta, Dinesh

    2016-01-01

    Aim: Human papilloma viruses (HPVs) are small DNA viruses that have been identified in periodontal pocket as well as gingival sulcus. High risk HPVs are also associated with a subset of head and neck carcinomas. HPV detection in periodontium has previously involved DNA detection. This study attempts to: (a) Detect the presence or absence of high risk HPV in marginal periodontiun by identifying E6/E7 messenger RNA (mRNA) in cells from samples obtained by periodontal pocket scraping. (b) Detect the percentage of HPV E6/E7 mRNA in cells of pocket scrapings, which is responsible for producing oncoproteins E6 and E7. Materials and Methods: Pocket scrapings from the periodontal pockets of eight subjects with generalized chronic periodontitis were taken the detection of presence or absence of E6, E7 mRNA was performed using in situ hybridization and flow cytometry. Results: HPV E6/E7 mRNA was detected in four of the eight samples. Conclusion: Presence of high risk human papillomaviruses in periodontal pockets patients of diagnosed with chronic periodontitis, not suffering from head and neck squamous cell carcinoma in the present day could link periodontitis to HPV related squamous cell carcinoma. Prevalence studies are needed detecting the presence of HPV in marginal periodontium as well as prospective studies of HPV positive periodontitis patients are required to explore this possible link. PMID:27143823

  1. Constructive Similarity of Soils

    Czech Academy of Sciences Publication Activity Database

    Koudelka, Petr

    Singapore : Design, CRC a iTEK CMS Web solutions, 2012 - (Phoon, K.; Beer, M.; Quek, S.; Pang, S.), s. 206-211 ISBN 978-981-07-2218-0. [APS on Structural Reliability and Its Application – Sustainable Civil Infrastructures /5./. Singapore (SG), 23.05.2012-25.05.2012] Grant ostatní: GA ČR(CZ) GAP105/11/1160 Institutional support: RVO:68378297 Keywords : model similarity * database of soil properties * soil similarity characteristic * statistical analysis * ultimate limit states Subject RIV: JM - Building Engineering

  2. Cognitive residues of similarity

    OpenAIRE

    OToole, Stephanie; Keane, Mark T.

    2013-01-01

    What are the cognitive after-effects of making a similarity judgement? What, cognitively, is left behind and what effect might these residues have on subsequent processing? In this paper, we probe for such after-effects using a visual search task, performed after a task in which pictures of real-world objects were compared. So, target objects were first presented in a comparison task (e.g., rate the similarity of this object to another) thus, presumably, modifying some of their features befor...

  3. Similarity of molecular shape.

    Science.gov (United States)

    Meyer, A Y; Richards, W G

    1991-10-01

    The similarity of one molecule to another has usually been defined in terms of electron densities or electrostatic potentials or fields. Here it is expressed as a function of the molecular shape. Formulations of similarity (S) reduce to very simple forms, thus rendering the computerised calculation straightforward and fast. 'Elements of similarity' are identified, in the same spirit as 'elements of chirality', except that the former are understood to be variable rather than present-or-absent. Methods are presented which bypass the time-consuming mathematical optimisation of the relative orientation of the molecules. Numerical results are presented and examined, with emphasis on the similarity of isomers. At the extreme, enantiomeric pairs are considered, where it is the dissimilarity (D = 1 - S) that is of consequence. We argue that chiral molecules can be graded by dissimilarity, and show that D is the shape-analog of the 'chirality coefficient', with the simple form of the former opening up numerical access to the latter. PMID:1770379

  4. The Qualitative Similarity Hypothesis

    Science.gov (United States)

    Paul, Peter V.; Lee, Chongmin

    2010-01-01

    Evidence is presented for the qualitative similarity hypothesis (QSH) with respect to children and adolescents who are d/Deaf or hard of hearing. The primary focus is on the development of English language and literacy skills, and some information is provided on the acquisition of English as a second language. The QSH is briefly discussed within…

  5. Mutational Mapping and Modeling of the Binding Site for (S)-Citalopram in the Human Serotonin Transporter

    DEFF Research Database (Denmark)

    Andersen, Jacob; Olsen, Lars; Hansen, Kasper B.;

    2010-01-01

    , and (S)-citalopram, which are competitive inhibitors of the transport function. Knowledge of the molecular details of the antidepressant binding sites in SERT has been limited due to lack of structural data on SERT. Here, we present a characterization of the (S)-citalopram binding pocket in human SERT...... (hSERT) using mutational and computational approaches. Comparative modeling and ligand docking reveal that (S)-citalopram fits into the hSERT substrate binding pocket, where (S)-citalopram can adopt a number of different binding orientations. We find, however, that only one of these binding modes is...... functionally relevant from studying the effects of 64 point mutations around the putative substrate binding site. The mutational mapping also identify novel hSERT residues that are crucial for (S)-citalopram binding. The model defines the molecular determinants for (S)-citalopram binding to hSERT and...

  6. The human fatty acid-binding protein family: Evolutionary divergences and functions

    Directory of Open Access Journals (Sweden)

    Smathers Rebecca L

    2011-03-01

    Full Text Available Abstract Fatty acid-binding proteins (FABPs are members of the intracellular lipid-binding protein (iLBP family and are involved in reversibly binding intracellular hydrophobic ligands and trafficking them throughout cellular compartments, including the peroxisomes, mitochondria, endoplasmic reticulum and nucleus. FABPs are small, structurally conserved cytosolic proteins consisting of a water-filled, interior-binding pocket surrounded by ten anti-parallel beta sheets, forming a beta barrel. At the superior surface, two alpha-helices cap the pocket and are thought to regulate binding. FABPs have broad specificity, including the ability to bind long-chain (C16-C20 fatty acids, eicosanoids, bile salts and peroxisome proliferators. FABPs demonstrate strong evolutionary conservation and are present in a spectrum of species including Drosophila melanogaster, Caenorhabditis elegans, mouse and human. The human genome consists of nine putatively functional protein-coding FABP genes. The most recently identified family member, FABP12, has been less studied.

  7. Structure of Bacillus subtilis γ-glutamyltranspeptidase in complex with acivicin: diversity of the binding mode of a classical and electrophilic active-site-directed glutamate analogue

    Energy Technology Data Exchange (ETDEWEB)

    Ida, Tomoyo [Osaka University, Toyonaka, Osaka 560-0043 (Japan); Suzuki, Hideyuki [Kyoto Institute of Technology, Goshokaido-cho, Matsugasaki, Sakyo-ku, Kyoto 606-8585 (Japan); Fukuyama, Keiichi [Osaka University, Toyonaka, Osaka 560-0043 (Japan); Hiratake, Jun [Kyoto University, Uji, Kyoto 611-0011 (Japan); Wada, Kei, E-mail: keiwada@med.miyazaki-u.ac.jp [University of Miyazaki, Miyazaki 889-1692 (Japan); Osaka University, Toyonaka, Osaka 560-0043 (Japan)

    2014-02-01

    The binding modes of acivicin, a classical and an electrophilic active-site-directed glutamate analogue, to bacterial γ-glutamyltranspeptidases were found to be diverse. γ-Glutamyltranspeptidase (GGT) is an enzyme that plays a central role in glutathione metabolism, and acivicin is a classical inhibitor of GGT. Here, the structure of acivicin bound to Bacillus subtilis GGT determined by X-ray crystallography to 1.8 Å resolution is presented, in which it binds to the active site in a similar manner to that in Helicobacter pylori GGT, but in a different binding mode to that in Escherichia coli GGT. In B. subtilis GGT, acivicin is bound covalently through its C3 atom with sp{sup 2} hybridization to Thr403 O{sup γ}, the catalytic nucleophile of the enzyme. The results show that acivicin-binding sites are common, but the binding manners and orientations of its five-membered dihydroisoxazole ring are diverse in the binding pockets of GGTs.

  8. Limiting Similarity Revisited

    OpenAIRE

    Szabo, P; Meszena, G.

    2005-01-01

    We reinvestigate the validity of the limiting similarity principle via numerical simulations of the Lotka-Volterra model. A Gaussian competition kernel is employed to describe decreasing competition with increasing difference in a one-dimensional phenotype variable. The simulations are initiated by a large number of species, evenly distributed along the phenotype axis. Exceptionally, the Gaussian carrying capacity supports coexistence of all species, initially present. In case of any other, d...

  9. Compression-based similarity

    OpenAIRE

    Vitányi, Paul

    2011-01-01

    First we consider pair-wise distances for literal objects consisting of finite binary files. These files are taken to contain all of their meaning, like genomes or books. The distances are based on compression of the objects concerned, normalized, and can be viewed as similarity distances. Second, we consider pair-wise distances between names of objects, like "red" or "christianity." In this case the distances are based on searches of the Internet. Such a search can be performed by any search...

  10. Binding of a fluorescence reporter and a ligand to an odorant-binding protein of the yellow fever mosquito, Aedes aegypti [v2; ref status: indexed, http://f1000r.es/4yp

    Directory of Open Access Journals (Sweden)

    Gabriel M. Leal

    2015-01-01

    Full Text Available Odorant-binding proteins (OBPs, also named pheromone-binding proteins when the odorant is a pheromone, are essential for insect olfaction. They solubilize odorants that reach the port of entry of the olfactory system, the pore tubules in antennae and other olfactory appendages. Then, OBPs transport these hydrophobic compounds through an aqueous sensillar lymph to receptors embedded on dendritic membranes of olfactory receptor neurons. Structures of OBPs from mosquito species have shed new light on the mechanism of transport, although there is considerable debate on how they deliver odorant to receptors. An OBP from the southern house mosquito, Culex quinquefasciatus, binds the hydrophobic moiety of a mosquito oviposition pheromone (MOP on the edge of its binding cavity. Likewise, it has been demonstrated that the orthologous protein from the malaria mosquito binds the insect repellent DEET on a similar edge of its binding pocket. A high school research project was aimed at testing whether the orthologous protein from the yellow fever mosquito, AaegOBP1, binds DEET and other insect repellents, and MOP was used as a positive control. Binding assays using the fluorescence reporter N-phenyl-1-naphtylamine (NPN were inconclusive. However, titration of NPN fluorescence emission in AaegOBP1 solution with MOP led to unexpected and intriguing results. Quenching was observed in the initial phase of titration, but addition of higher doses of MOP led to a stepwise increase in fluorescence emission coupled with a blue shift, which can be explained at least in part by formation of MOP micelles to house stray NPN molecules.

  11. A Low Affinity Ground State Conformation for the Dynein Microtubule Binding Domain*

    OpenAIRE

    McNaughton, Lynn; Tikhonenko, Irina; Banavali, Nilesh K.; LeMaster, David M.; Koonce, Michael P.

    2010-01-01

    Dynein interacts with microtubules through a dedicated binding domain that is dynamically controlled to achieve high or low affinity, depending on the state of nucleotide bound in a distant catalytic pocket. The active sites for microtubule binding and ATP hydrolysis communicate via conformational changes transduced through a ∼10-nm length antiparallel coiled-coil stalk, which connects the binding domain to the roughly 300-kDa motor core. Recently, an x-ray structure of the murine cytoplasmic...

  12. Identification of Essential Cannabinoid-binding Domains: STRUCTURAL INSIGHTS INTO EARLY DYNAMIC EVENTS IN RECEPTOR ACTIVATION*

    OpenAIRE

    Shim, Joong-Youn; Bertalovitz, Alexander C.; Kendall, Debra A.

    2011-01-01

    The classical cannabinoid agonist HU210, a structural analog of (−)-Δ9-tetrahydrocannabinol, binds to brain cannabinoid (CB1) receptors and activates signal transduction pathways. To date, an exact molecular description of the CB1 receptor is not yet available. Utilizing the minor binding pocket of the CB1 receptor as the primary ligand interaction site, we explored HU210 binding using lipid bilayer molecular dynamics (MD) simulations. Among the potential ligand contact residues, we identifie...

  13. Three Dimensional Flow and Pressure Patterns in a Single Pocket of a Hydrostatic Journal Bearing

    Science.gov (United States)

    Braun, M. Jack; Dzodzo, Milorad B.

    1996-01-01

    The flow in a hydrostatic pocket is described by a mathematical model that uses the three dimensional Navier-Stokes equations written in terms of the primary variables, u, v, w, and p. Using a conservative formulation, a finite volume multi-block method is applied through a collocated, body fitted grid. The flow is simulated in a shallow pocket with a depth/length ratio of 0.02. The flow structures obtained and described by the authors in their previous two dimensional models are made visible in their three dimensional aspect for the Couette flow. It has been found that the flow regimes formed central and secondary vortical cells with three dimensional corkscrew-like structures that lead the fluid on an outward bound path in the axial direction of the pocket. The position of the central vortical cell center is at the exit region of the capillary restrictor feedline. It has also been determined that a fluid turn around zone occupies all the upstream space between the floor of the pocket and the runner, thus preventing any flow exit through the upstream port. The corresponding pressure distribution under the shaft presented as well. It was clearly established that for the Couette dominated case the pressure varies significantly in the pocket in the circumferential direction, while its variation is less pronounced axially.

  14. A simple system for the measurement of natural radiation (γ-ray) using a pocket computer

    International Nuclear Information System (INIS)

    A simple and convenient system has been constructed for the measurement of natural radiation (γ-ray). A pocket computer and a dose rate meter (commercial name: HORIBA HAKARUKUN) were used. The dose meter detects the γ-rays with energy from 150 keV to 3 MeV. An interface-circuit was made to count the number of detected γ-rays and to connect the pocket computer with dose meter. The counts of γ-rays for each regular interval time (for example 10 sec) were stored in memory of pocket computer. About 3600 data can be stored in memory. Then if we count each 10 sec, we can measure continuously for 10 hours. The system (dose meter, interface-circuit and pocket computer) is operated by battery and can be encased in a compact tool box for the field work. The data stored in pocket computer were transfered to personal computer with RS-232 C line. The changes of the counts of γ-rays were measured at some places in Fukui National College of Technology and in the JR-train from Kanazawa to Nagaoka etc. Some reasonable results were obtained. (author)

  15. Iranian Households’ Payments on Food and Health Out-of-Pocket Expenditures: Evidence of Inequality

    Directory of Open Access Journals (Sweden)

    Hesam GHIASVAND

    2015-10-01

    Full Text Available Background: Inequality in households’ payments on food and health expenditures presents the accessibility and utili-zation patterns between them. This study investigated the Iranian rural and urban households’ inequality in payments on food and Out-of-Pocket health expenditures from 1998 to 2012.Methods: This descriptive study was conducted through the analysis of Iranian Statistics Centre data on Iranian households’ income and expenditures. The Gini Coefficients, Concentration and Kakwani indices have been calculat-ed for Iranian rural and urban households’ Out-of-Pocket health and food expenditures.Results: The means of Iranian rural and urban total consumption expenditures inequality were 0.48 and 0.48, respec-tively. The means of concentration index of food expenditures for rural and urban regions were 0.35 and 0.34, respec-tively. The means of Out-of-Pocket payments for health services for rural and urban regions were 0.51 and 0.5, re-spectively. Finally the means of Kakwani index of Out-of-Pocket health payments in rural and urban households were -0.005 and -0.018, respectively.Conclusion: There are relative high levels of inequality in Iranian households’ payments on food and Out-of-Pocket health expenditures.

  16. Medicare Advantage Members' Expected Out-Of-Pocket Spending For Inpatient And Skilled Nursing Facility Services.

    Science.gov (United States)

    Keohane, Laura M; Grebla, Regina C; Mor, Vincent; Trivedi, Amal N

    2015-06-01

    Inpatient and skilled nursing facility (SNF) cost sharing in Medicare Advantage (MA) plans may reduce unnecessary use of these services. However, large out-of-pocket expenses potentially limit access to care and encourage beneficiaries at high risk of needing inpatient and postacute care to avoid or leave MA plans. In 2011 new federal regulations restricted inpatient and skilled nursing facility cost sharing and mandated limits on out-of-pocket spending in MA plans. After these regulations, MA members in plans with low premiums averaged $1,758 in expected out-of-pocket spending for an episode of seven hospital days and twenty skilled nursing facility days. Among members with the same low-premium plan in 2010 and 2011, 36 percent of members belonged to plans that added an out-of-pocket spending limit in 2011. However, these members also had a $293 increase in average cost sharing for an inpatient and skilled nursing facility episode, possibly to offset plans' expenses in financing out-of-pocket limits. Some MA beneficiaries may still have difficulty affording acute and postacute care despite greater regulation of cost sharing. PMID:26056208

  17. Treatment of Fingertip Amputation in Adults by Palmar Pocketing of the Amputated Part

    Directory of Open Access Journals (Sweden)

    Mi Sun Jung

    2012-07-01

    Full Text Available Background First suggested by Brent in 1979, the pocket principle is an alternative methodfor patients for whom a microsurgical replantation is not feasible. We report the successfulresults of a modified palmar pocket method in adults.Methods Between 2004 and 2008, we treated 10 patients by nonmicrosurgical replantationusing palmar pocketing. All patients were adults who sustained a complete fingertip amputationfrom the tip to lunula in a digits. In all of these patients, the amputation occurred due to a crushor avulsion-type injury, and a microsurgical replantation was not feasible. We used the palmarpocketing method following a composite graft in these patients and prepared the pocket in thesubcutaneous layer of the ipsilateral palm.Results Of a total of 10 cases, nine had complete survival of the replantation and one had20% partial necrosis. All of the cases were managed to conserve the fingernails, which led toacceptable cosmetic results.Conclusions A composite graft and palmar pocketing in adult cases of fingertip injuryconstitute a simple, reliable operation for digital amputation extending from the tip to thelunula. These methods had satisfactory results.

  18. The qualitative similarity hypothesis.

    Science.gov (United States)

    Paul, Peter V; Lee, Chongmin

    2010-01-01

    Evidence is presented for the qualitative similarity hypothesis (QSH) with respect to children and adolescents who are d/Deaf or hard of hearing. The primary focus is on the development of English language and literacy skills, and some information is provided on the acquisition of English as a second language. The QSH is briefly discussed within the purview of two groups of cognitive models: those that emphasize the cognitive development of individuals and those that pertain to disciplinary or knowledge structures. It is argued that the QSH has scientific merit with implications for classroom instruction. Future research should examine the validity of the QSH in other disciplines such as mathematics and science and should include perspectives from social as well as cognitive models. PMID:20415280

  19. Self Similar Optical Fiber

    Science.gov (United States)

    Lai, Zheng-Xuan

    This research proposes Self Similar optical fiber (SSF) as a new type of optical fiber. It has a special core that consists of self similar structure. Such a structure is obtained by following the formula for generating iterated function systems (IFS) in Fractal Theory. The resulted SSF can be viewed as a true fractal object in optical fibers. In addition, the method of fabricating SSF makes it possible to generate desired structures exponentially in numbers, whereas it also allows lower scale units in the structure to be reduced in size exponentially. The invention of SSF is expected to greatly ease the production of optical fiber when a large number of small hollow structures are needed in the core of the optical fiber. This dissertation will analyze the core structure of SSF based on fractal theory. Possible properties from the structural characteristics and the corresponding applications are explained. Four SSF samples were obtained through actual fabrication in a laboratory environment. Different from traditional conductive heating fabrication system, I used an in-house designed furnace that incorporated a radiation heating method, and was equipped with automated temperature control system. The obtained samples were examined through spectrum tests. Results from the tests showed that SSF does have the optical property of delivering light in a certain wavelength range. However, SSF as a new type of optical fiber requires a systematic research to find out the theory that explains its structure and the associated optical properties. The fabrication and quality of SSF also needs to be improved for product deployment. As a start of this extensive research, this dissertation work opens the door to a very promising new area in optical fiber research.

  20. The $^{13}C$-pockets in AGB Stars and Their Fingerprints in Mainstream SiC Grains

    CERN Document Server

    Liu, Nan; Gallino, Roberto; Savina, Michael R; Bisterzo, Sara; Gyngard, Frank; Pellin, Michael J; Dauphas, Nicolas

    2015-01-01

    We identify three isotopic tracers that can be used to constrain the $^{13}C$-pocket and show the correlated isotopic ratios of Sr and Ba in single mainstream presolar SiC grains. These newly measured data can be explained by postprocess AGB model calculations with large $^{13}C$-pockets with a range of relatively low $^{13}C$ concentrations, which may suggest that multiple mixing processes contributed to the $^{13}C$-pocket formation in parent AGB stars.

  1. Co-current air-water flow in downward sloping pipes: Transport of capacity reducing gas pockets in wastewater mains

    OpenAIRE

    Pothof, I.W.M.

    2011-01-01

    Air-water flow is an undesired condition in many systems for the transportation of water or wastewater. Air in storm water tunnels may get trapped and negatively affect the system. Air pockets in hydropower tunnels or sewers may cause blow-back events and inadmissible pressure spikes. Water pipes and wastewater pressure mains in particular are subject to air pocket formation in downward-sloping reaches, such as inverted siphons or terrain slopes. Air pocket accumulation causes energy losses a...

  2. 趁热打铁——联想Pocket Yoga Netbook

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    闹得沸沸扬扬的联想新款上网本PocketYoga不管是外观还是尺寸都像极了索尼VAIOP系列,造型与标准的商务信封差不多,难道是想趁着VAIOP市场火爆的东风也热闹一把?与VAIOP不同的是,PocketYoga的显示屏可以360度旋转,从而变成平板电脑。PocketYoga拥有奢华的皮革外壳,还安装了一个超广角触摸屏和边角齐平的按键。从以上方面来看,

  3. Neurology diagnostics security and terminal adaptation for PocketNeuro project.

    Science.gov (United States)

    Chemak, C; Bouhlel, M-S; Lapayre, J-C

    2008-09-01

    This paper presents new approaches of medical information security and terminal mobile phone adaptation for the PocketNeuro project. The latter term refers to a project created for the management of neurological diseases. It consists of transmitting information about patients ("desk of patients") to a doctor's mobile phone during a visit and examination of a patient. These new approaches for the PocketNeuro project were analyzed in terms of medical information security and adaptation of the diagnostic images to the doctor's mobile phone. Images were extracted from a DICOM library. Matlab and its library were used as software to test our approaches and to validate our results. Experiments performed on a database of 30 256 x 256 pixel-sized neuronal medical images indicated that our new approaches for PocketNeuro project are valid and support plans for large-scale studies between French and Swiss hospitals using secured connections. PMID:18817496

  4. PROSTAGLANDIN E2 LEVEL IN GINGIVAL CREVICULAR FLUID AND ITS RELATION TO THE PERIODONTAL POCKET DEPTH IN PATIENTS WITH PERIODONTITIS

    Institute of Scientific and Technical Information of China (English)

    周坚; 邹石莹; 赵戚; 赵玉霞

    1994-01-01

    Prostaglandin E2(PGE2)levels in gingival crevicular fluid (GCF)of 46 normal controls and 90 patients suf-fering from periodontitis with different periodontal pocket depths were measured by radioimmunoassay (RIA).The results demonstrated that PGE2 levels in the periodontal pockets are higher in patients with peri-odontitis.The PGE2 level rises as the periodontal pocket deepens,especially in casses where the periodontal pocket depth exceeds 6 mm.This study shows that PGE2 level is significantly related to the severity of bone destruc-tion in periodontitis.

  5. How the Proximal Pocket May Influence the Enantiospecificities of Chloroperoxidase-Catalyzed Epoxidations of Olefins

    Science.gov (United States)

    Morozov, Alexander N.; Chatfield, David C.

    2016-01-01

    Chloroperoxidase-catalyzed enantiospecific epoxidations of olefins are of significant biotechnological interest. Typical enantiomeric excesses are in the range of 66%–97% and translate into free energy differences on the order of 1 kcal/mol. These differences are generally attributed to the effect of the distal pocket. In this paper, we show that the influence of the proximal pocket on the electron transfer mechanism in the rate-limiting event may be just as significant for a quantitatively accurate account of the experimentally-measured enantiospecificities. PMID:27517911

  6. The Klebsiella pneumoniae O12 ATP-binding Cassette (ABC) Transporter Recognizes the Terminal Residue of Its O-antigen Polysaccharide Substrate.

    Science.gov (United States)

    Mann, Evan; Mallette, Evan; Clarke, Bradley R; Kimber, Matthew S; Whitfield, Chris

    2016-04-29

    Export of the Escherichia coli serotype O9a O-antigenic polysaccharides (O-PS) involves an ATP-binding cassette (ABC) transporter. The process requires a non-reducing terminal residue, which is recognized by a carbohydrate-binding module (CBM) appended to the C terminus of the nucleotide-binding domain of the transporter. Here, we investigate the process in Klebsiella pneumoniae serotype O12 (and Raoultella terrigena ATCC 33257). The O12 polysaccharide is terminated at the non-reducing end by a β-linked 3-deoxy-d-manno-oct-2-ulosonic acid (Kdo) residue. The O12 ABC transporter also binds its cognate O-PS via a CBM, and export is dependent on the presence of the terminal β-Kdo residue. The overall structural architecture of the O12 CBM resembles the O9a prototype, but they share only weak sequence similarity, and the putative binding pocket for the O12 glycan is different. Removal of the CBM abrogated O-PS transport, but export was restored when the CBM was expressed in trans with the mutant CBM-deficient ABC transporter. These results demonstrate that the CBM-mediated substrate-recognition mechanism is evolutionarily conserved and can operate with glycans of widely differing structures. PMID:26934919

  7. Use of 2D NMR, protein engineering, and molecular modeling to study the hapten-binding site of an antibody Fv fragment against 2-phenyloxazolone

    International Nuclear Information System (INIS)

    Two-dimensional (2D) 1H NMR spectroscopy was used to study the hapten-binding site of a recombinant antibody Fv fragment expressed in Escherichia coli. Point mutations of residues in the CDR loops of the Fv fragment were designed in order to investigate their influence on hapten binding and to make site-specific assignments of aromatic NMR proton signals. Two tyrosines giving NOEs to the ligand 2-phenyloxazolone were identified, residue 33 in CDR1 of the heavy chain and residue 32 in CDR1 of the light chain. The benzyl portion of 2-phenyloxazolone is located between these two residues. The binding site is close to the surface of the Fv fragment. Comparison with a different anti-2-phenyloxazolone antibody, the crystal structure of which has recently been solved, shows that the general location of the hapten-binding site in both antibodies is similar. However, in the crystallographically solved antibody, the hapten is bound farther from the surface in a pocket created by a short CDR3 loop of the heavy chain. In the binding site identified in the Fv fragment studied in this report, this space is probably filled by the extra seven residues of the CDR3

  8. Structural and functional insights into the ligand-binding domain of a nonduplicated retinoid X nuclear receptor from the invertebrate chordate amphioxus.

    Science.gov (United States)

    Tocchini-Valentini, Giuseppe D; Rochel, Natacha; Escriva, Hector; Germain, Pierre; Peluso-Iltis, Carole; Paris, Mathilde; Sanglier-Cianferani, Sarah; Van Dorsselaer, Alain; Moras, Dino; Laudet, Vincent

    2009-01-16

    Retinoid X nuclear receptors (RXRs), as well as their insect orthologue, ultraspiracle protein (USP), play an important role in the transcription regulation mediated by the nuclear receptors as the common partner of many other nuclear receptors. Phylogenetic and structural studies have shown that the several evolutionary shifts have modified the ligand binding ability of RXRs. To understand the vertebrate-specific character of RXRs, we have studied the RXR ligand-binding domain of the cephalochordate amphioxus (Branchiostoma floridae), an invertebrate chordate that predates the genome duplication that produced the three vertebrates RXRs (alpha, beta, and gamma). Here we report the crystal structure of a novel apotetramer conformation of the AmphiRXR ligand-binding domain, which shows some similarity with the structures of the arthropods RXR/USPs. AmphiRXR adopts an apo antagonist conformation with a peculiar conformation of helix H11 filling the binding pocket. In contrast to the arthropods RXR/USPs, which cannot be activated by any RXR ligands, our functional data show that AmphiRXR, like the vertebrates/mollusk RXRs, is able to bind and be activated by RXR ligands but less efficiently than vertebrate RXRs. Our data suggest that amphioxus RXR is, functionally, an intermediate between arthropods RXR/USPs and vertebrate RXRs. PMID:18986992

  9. Imatinib binding to human c-Src is coupled to inter-domain allostery and suggests a novel kinase inhibition strategy.

    Science.gov (United States)

    Tsutsui, Yuko; Deredge, Daniel; Wintrode, Patrick L; Hays, Franklin A

    2016-01-01

    Imatinib (Gleevec), a non-receptor tyrosine kinase inhibitor (nRTKI), is one of the most successful anti-neoplastic drugs in clinical use. However, imatinib-resistant mutations are increasingly prevalent in patient tissues and driving development of novel imatinib analogs. We present a detailed study of the conformational dynamics, in the presence and absence of bound imatinib, for full-length human c-Src using hydrogen-deuterium exchange and mass spectrometry. Our results demonstrate that imatinib binding to the kinase domain effects dynamics of proline-rich or phosphorylated peptide ligand binding sites in distal c-Src SH3 and SH2 domains. These dynamic changes in functional regulatory sites, distal to the imatinib binding pocket, show similarities to structural transitions involved in kinase activation. These data also identify imatinib-sensitive, and imatinib-resistant, mutation sites. Thus, the current study identifies novel c-Src allosteric sites associated with imatinib binding and kinase activation and provide a framework for follow-on development of TKI binding modulators. PMID:27480221

  10. Characterization of the differences in the cyclopiazonic acid binding mode to mammalian and P. Falciparum Ca2+ pumps: a computational study.

    KAUST Repository

    Di Marino, Daniele

    2015-03-01

    Despite the investments in malaria research, an effective vaccine has not yet been developed and the causative parasites are becoming increasingly resistant to most of the available drugs. PfATP6, the sarco/endoplasmic reticulum Ca2+ pump (SERCA) of P. falciparum, has been recently genetically validated as a potential antimalarial target and cyclopiazonic acid (CPA) has been found to be a potent inhibitor of SERCAs in several organisms, including P. falciparum. In position 263, PfATP6 displays a leucine residue, whilst the corresponding position in the mammalian SERCA is occupied by a glutamic acid. The PfATP6 L263E mutation has been studied in relation to the artemisinin inhibitory effect on P. falciparum and recent studies have provided evidence that the parasite with this mutation is more susceptible to CPA. Here, we characterized, for the first time, the interaction of CPA with PfATP6 and its mammalian counterpart to understand similarities and differences in the mode of binding of the inhibitor to the two Ca2+ pumps. We found that, even though CPA does not directly interact with the residue in position 263, the presence of a hydrophobic residue in this position in PfATP6 rather than a negatively charged one, as in the mammalian SERCA, entails a conformational arrangement of the binding pocket which, in turn, determines a relaxation of CPA leading to a different binding mode of the compound. Our findings highlight differences between the plasmodial and human SERCA CPA-binding pockets that may be exploited to design CPA derivatives more selective toward PfATP6.

  11. Profiling Protein Kinases and Other ATP Binding Proteins in Arabidopsis Using Acyl-ATP Probes*

    OpenAIRE

    Villamor, J. G.; Kaschani, F.; Colby, T; Oeljeklaus, J.; Zhao, D; Kaiser, M.; Patricelli, M. P.; R. A. L. van der Hoorn

    2013-01-01

    Many protein activities are driven by ATP binding and hydrolysis. Here, we explore the ATP binding proteome of the model plant Arabidopsis thaliana using acyl-ATP (AcATP)1 probes. These probes target ATP binding sites and covalently label lysine residues in the ATP binding pocket. Gel-based profiling using biotinylated AcATP showed that labeling is dependent on pH and divalent ions and can be competed by nucleotides. The vast majority of these AcATP-labeled proteins are known ATP binding prot...

  12. Binding Procurement

    Science.gov (United States)

    Rao, Gopalakrishna M.; Vaidyanathan, Hari

    2007-01-01

    This viewgraph presentation reviews the use of the binding procurement process in purchasing Aerospace Flight Battery Systems. NASA Engineering and Safety Center (NESC) requested NASA Aerospace Flight Battery Systems Working Group to develop a set of guideline requirements document for Binding Procurement Contracts.

  13. Kinetic properties and heme pocket structure of two domains of the polymeric hemoglobin of Artemia in comparison with the native molecule.

    Science.gov (United States)

    Borhani, Heshmat Akbari; Berghmans, Herald; Trashin, Stanislav; De Wael, Karolien; Fago, Angela; Moens, Luc; Habibi-Rezaei, Mehran; Dewilde, Sylvia

    2015-10-01

    In this project, we studied some physicochemical properties of two different globin domains of the polymeric hemoglobin of the brine shrimp Artemia salina and compared them with those of the native molecule. Two domains (AsHbC1D1 and AsHbC1D5) were cloned and expressed in BL21(DE3)pLysS strain of Escherichia coli. The recombinant proteins as well as the native hemoglobin (AfHb) were purified from bacteria and frozen Artemia, respectively by standard chromatographic methods and assessed by SDS-PAGE. The heme environment of these proteins was studied by optical spectroscopy and ligand-binding kinetics (e.g. CO association and O2 binding affinity) were measured for the two recombinant proteins and the native hemoglobin. This indicates that the CO association rate for AsHbC1D1 is higher than that of AsHbC1D5 and AfHb, while the calculated P50 value for AsHbC1D1 is lower than that of AsHbC1D5 and AfHb. The geminate and bimolecular rebinding parameters indicate a significant difference between both domains. Moreover, EPR results showed that the heme pocket in AfHb is in a more closed conformation than the heme pocket in myoglobin. Finally, the reduction potential of -0.13V versus the standard hydrogen electrode was determined for AfHb by direct electrochemical measurements. It is about 0.06V higher than the potential of the single domain AsHbC1D5. This work shows that each domain in the hemoglobin of Artemia has different characteristics of ligand binding. PMID:26004089

  14. Steered Molecular Dynamics Simulation on the Binding of NNRTI to HIV-1 RT

    Energy Technology Data Exchange (ETDEWEB)

    Shen, Lingling; Shen, Jianhua; Luo, Xiaomin; Cheng, Feng; Xu, Yechun; Chen, Kaixian; Arnold, Edward; Ding, Jianping; Jiang, Hualiang

    2003-06-01

    HIV-1 reverse transcriptase (RT) is the primary target for anti-AIDS chemotherapy. Nonnucleoside RT inhibitors (NNRTIs) are very potent and most promising anti-AIDS drugs that specifically inhibit HIV-1 RT. The binding and unbinding processes of alpha-APA, an NNRTI, have been studied using nanosecond conventional molecular dynamics and steered molecular dynamics simulations. The simulation results show that the unbinding process of alpha-APA consists of three phases based on the position of alpha-APA in relation to the entrance of the binding pocket. When alpha-APA is bound in the binding pocket, the hydrophobic interactions between HIV-1 RT and alpha-APA dominate the binding; however, the hydrophilic interactions (both direct and water-bridged hydrogen bonds) also contribute to the stabilizing forces. Whereas Tyr-181 makes significant hydrophobic interactions with alpha-APA, Tyr-188 forms a strong hydrogen bond with the acylamino group (N14) of alpha-APA. These two residues have very flexible side chains and appear to act as two ''flexible clamps'' discouraging alpha-APA to dissociate from the binding pocket. At the pocket entrance, two relatively inflexible residues, Val-179 and Leu-100, gauge the openness of the entrance and form the bottleneck of the inhibitor-unbinding pathway. Two special water molecules at the pocket entrance appear to play important roles in inhibitor recognition of binding and unbinding. These water molecules form water bridges between the polar groups of the inhibitor and the residues around the entrance, and between the polar groups of the inhibitor themselves. The water-bridged interactions not only induce the inhibitor to adopt an energetically favorable conformation so the inhibitor can pass through the pocket entrance, but also stabilize the binding of the inhibitor in the pocket to prevent the inhibitor's dissociation. The complementary steered molecular dynamics and conventional molecular dynamics

  15. Investigation of dielectric pocket induced variations in tunnel field effect transistor

    Science.gov (United States)

    Upasana; Narang, Rakhi; Saxena, Manoj; Gupta, Mridula

    2016-04-01

    The performance of conventional Tunnel FETs struggling from ambipolar issues, insufficient on-current, lower transconductance value, higher delay and lower cut off frequency has been improved by introducing several material and device engineering concepts in past few years. Keeping this in view, another interesting and reliable option i.e. Dielectric Pocket TFET (featuring a dielectric pocket placement near tunneling junction) has been comprehensively and qualitatively demonstrated using ATLAS device simulator. The architecture has been explored in terms of various device electrostatic parameters such as potential, energy band profile, electron and hole concentration, electric field variation and band to band generation rate (GBTB) near the tunneling junction where the Dielectric Pocket (DP) has been introduced. Subsequently, a detailed investigation by changing the position and dielectric constant of pocket at respective junctions has been made where DP induced variations in drain current, transconductance and parasitic capacitance have been examined. The work highlights major improvements over conventional TFET in terms of lower subthreshold swing and threshold voltage, higher drain current and transconductance, improved on-to-off current ratio, suppressed ambipolar conduction and improved dynamic power dissipation issues for low voltage analog and digital applications.

  16. Access to Rural Mental Health Services: Service Use and Out-of-Pocket Costs

    Science.gov (United States)

    Ziller, Erika C.; Anderson, Nathaniel J.; Coburn, Andrew F.

    2010-01-01

    Purpose: To examine rural-urban differences in the use of mental health services (mental health and substance abuse office visits, and mental health prescriptions) and in the out-of-pocket costs paid for these services. Methods: The pooled 2003 and 2004 Medical Expenditure Panel Surveys were used to assess differences in mental health service use…

  17. Do Nurse-Led Skill Training Interventions Affect Informal Caregivers' Out-of-Pocket Expenditures?

    Science.gov (United States)

    Van Houtven, Courtney Harold; Thorpe, Joshua M.; Chestnutt, Deborah; Molloy, Margory; Boling, John C.; Davis, Linda Lindsey

    2013-01-01

    Purpose of the Study: This paper is a report of a study of the Assistance, Support, and Self-health Initiated through Skill Training (ASSIST) randomized control trial. The aim of this paper is to understand whether participating in ASSIST significantly changed the out-of-pocket (OOP) costs for family caregivers of Alzheimer's disease (AD) or…

  18. Adaptation of a pocket PC for use as a wearable voice dosimeter

    NARCIS (Netherlands)

    Popolo, PS; Svec, Jan G.; Titze, Ingo R.

    2005-01-01

    This article deals with the adaptation of a commercially available Pocket PC for use a wearable device that measures the vocal dose of teachers as a voice dosimeter, or other individuals on the job, at home, and elsewhere during the course of an entire day. An engineering approach for designing a vo

  19. A Mobile Computing Solution for Collecting Functional Analysis Data on a Pocket PC

    Science.gov (United States)

    Jackson, James; Dixon, Mark R.

    2007-01-01

    The present paper provides a task analysis for creating a computerized data system using a Pocket PC and Microsoft Visual Basic. With Visual Basic software and any handheld device running the Windows MOBLE operating system, this task analysis will allow behavior analysts to program and customize their own functional analysis data-collection…

  20. The Single Needle Lockstitch Machine. [Constructing and Setting Pockets.] Module 9.

    Science.gov (United States)

    South Carolina State Dept. of Education, Columbia. Office of Vocational Education.

    This module on constructing and setting pockets, one in a series on the single needle lockstitch sewing machine for student self-study, contains three sections. Each section includes the following parts: an introduction, directions, an objective, learning activities, student information, student self-check, check-out activities, and an…

  1. Adaptation of a Pocket PC for Use as a Wearable Voice Dosimeter

    Science.gov (United States)

    Popolo, Peter S.; Svec, Jan G.; Titze, Ingo R.

    2005-01-01

    This article deals with the adaptation of a commercially available Pocket PC for use as a voice dosimeter, a wearable device that measures the vocal dose of teachers or other individuals on the job, at home, and elsewhere during the course of an entire day. An engineering approach for designing a voice dosimeter is described, and design data are…

  2. PREPARING PERFECT PROJECT PLANS: A POCKET GUIDE FOR THE PREPARATION OF QUALITY ASSURANCE PROJECT PLANS

    Science.gov (United States)

    This Pocket Guide helps you prepare Quality Assurance (QA) Project Plans thoroughly and easily. he Risk Reduction Engineering Laboratory (RREL) utilizes a four-tiered project category approach in order to more effectively focus QA with respect to the intended use of the data and ...

  3. Proton NMR investigation of heme pocket mobility in hemoglobin via hydrogen isotope exchange kinetics

    International Nuclear Information System (INIS)

    Dynamic mobility of heme cavity, the active site of Hb, was investigated by analyzing the hydrogen isotope exchange kinetics of the proximal histidyl ring NH of various kinds of Hbs with the aid of the high field Fourier Transform 1 H NMR spectroscopy. The exchange reaction occurs faster in oxy or R-state Hb than in deoxy or T-state Hb and there exists a good correlation between the oxygen affinity of Hb and the heme pocket mobility reflected in the hydrogen exchange rate. The effect of pH on the exchange is dramatically different for the two subunits of Hb A. Studying the exchange characteristics of mutant Hbs and chemically modified Hbs not only showed the existence of three well-defined localized paths for transmission of conformational changes between different heme pockets through a1b2 subunit interface, but also indicated that the heme pocket mobility is regulated by the quaternary state of Hb as well as by the ligation state of Hb. Finally, the effect of the quaternary state on the heme pocket mobility is separated from that of the ligation by following the exchange reactions in Hbs where only their quaternary structure transition can be achieved without changing their ligation states by adjusting experimental conditions such as adding inositol hexaphosphate

  4. Identifying features of pocket parks that may be related to health promoting use

    DEFF Research Database (Denmark)

    Peschardt, Karin Kragsig; Stigsdotter, Ulrika K.; Schipperijn, Jasper

    2016-01-01

    uses. The relationship between the two types of use and the shape, size, noise level, greenness, as well as ‘elements’ (paved and unpaved trails, café, historical feature, table, other seating than benches, flowerbeds, view outside park, playground) in nine pocket parks in Copenhagen were analysed. The...

  5. The function and three-dimensional structure of a thromboxane A2/cysteinyl leukotriene-binding protein from the saliva of a mosquito vector of the malaria parasite.

    Directory of Open Access Journals (Sweden)

    Patricia H Alvarenga

    Full Text Available The highly expressed D7 protein family of mosquito saliva has previously been shown to act as an anti-inflammatory mediator by binding host biogenic amines and cysteinyl leukotrienes (CysLTs. In this study we demonstrate that AnSt-D7L1, a two-domain member of this group from Anopheles stephensi, retains the CysLT binding function seen in the homolog AeD7 from Aedes aegypti but has lost the ability to bind biogenic amines. Unlike any previously characterized members of the D7 family, AnSt-D7L1 has acquired the important function of binding thromboxane A(2 (TXA(2 and its analogs with high affinity. When administered to tissue preparations, AnSt-D7L1 abrogated Leukotriene C(4 (LTC(4-induced contraction of guinea pig ileum and contraction of rat aorta by the TXA(2 analog U46619. The protein also inhibited platelet aggregation induced by both collagen and U46619 when administered to stirred platelets. The crystal structure of AnSt-D7L1 contains two OBP-like domains and has a structure similar to AeD7. In AnSt-D7L1, the binding pocket of the C-terminal domain has been rearranged relative to AeD7, making the protein unable to bind biogenic amines. Structures of the ligand complexes show that CysLTs and TXA(2 analogs both bind in the same hydrophobic pocket of the N-terminal domain. The TXA(2 analog U46619 is stabilized by hydrogen bonding interactions of the ω-5 hydroxyl group with the phenolic hydroxyl group of Tyr 52. LTC(4 and occupies a very similar position to LTE(4 in the previously determined structure of its complex with AeD7. As yet, it is not known what, if any, new function has been acquired by the rearranged C-terminal domain. This article presents, to our knowledge, the first structural characterization of a protein from mosquito saliva that inhibits collagen mediated platelet activation.

  6. Ondansetron and Granisetron Binding Orientation in the 5-HT3 Receptor Determined by Unnatural Amino Acid Mutagenesis

    Science.gov (United States)

    Duffy, Noah H.; Lester, Henry A.; Dougherty, Dennis A.

    2012-01-01

    The serotonin type 3 receptor (5-HT3R) is a ligand-gated ion channel that mediates fast synaptic transmission in the central and peripheral nervous systems. The 5-HT3R is a therapeutic target, and the clinically available drugs ondansetron and granisetron inhibit receptor activity. Their inhibitory action is through competitive binding to the native ligand binding site, although the binding orientation of the drugs at the receptor has been a matter of debate. Here we heterologously express mouse 5-HT3A receptors in Xenopus oocytes and use unnatural amino acid mutagenesis to establish a cation-π interaction for both ondansetron and granisetron to tryptophan 183 in the ligand binding pocket. This cation-π interaction establishes a binding orientation for both ondansetron and granisetron within the binding pocket. PMID:22873819

  7. Influences of lubricant pocket geometry and working conditions upon micro lubrication mechanisms in upsetting and strip drawing

    DEFF Research Database (Denmark)

    Shimizu, Ichiro; Martins, P. A. F.; Bay, Niels; Andresen, Jan Lasson; Bech, Jakob Ilsted

    2010-01-01

    Micro-lubricant pockets located in the surface of plastically deforming workpieces are recognised to improve the performance of fluid lubrication in a metal-forming process. This work investigates the joint influence of pocket geometry and process working conditions on micro-lubrication mechanism...

  8. Health care consumers’ opinions on different variants of out-of-pocket payments. A cross-sectional questionnaire study .

    NARCIS (Netherlands)

    Reitsma, M.; Jong, J. de

    2014-01-01

    Background: Health care expenditures are rising faster than the resources in many countries. One of the tools to reduce this expenditures is by introducing out-of-pocket payments. With these payments insured have to pay (part of) the costs of health care themselves. One of the aims of out-of pocket

  9. Enhanced performance of GeSn source-pocket tunnel field-effect transistors for low-power applications

    Science.gov (United States)

    Liu, Lei; Liang, Renrong; Wang, Jing; Xu, Jun

    2016-07-01

    Germanium–tin (GeSn) source-pocket tunnel field-effect transistors (TFETs) are comprehensively investigated by numerical device simulations at low supply voltages. Device configurations with homo- and hetero-tunneling junctions (TJ) are analyzed and compared. It is shown that direct-gap GeSn alloys are favorable for increasing the source-pocket tunneling rate. Increasing the source Sn composition of the device may aid the on-state current increase, but the subthreshold swing (SS) is degraded because of the reduced band gap. At ultrascaled supply voltages, the GeSn hetero-TJ TFET with higher pocket Sn composition exhibits the best performance and SS, and the device performance can be further improved by increasing the Sn composition in the pocket region. These simulation results could be used to understand and optimize the performance of GeSn source-pocket TFETs, which are very promising electronic devices for low-power applications.

  10. Chicken avidin-related proteins show altered biotin-binding and physico-chemical properties as compared with avidin.

    Science.gov (United States)

    Laitinen, Olli H; Hytönen, Vesa P; Ahlroth, Mervi K; Pentikäinen, Olli T; Gallagher, Ciara; Nordlund, Henri R; Ovod, Vladimir; Marttila, Ari T; Porkka, Eevaleena; Heino, Sanna; Johnson, Mark S; Airenne, Kari J; Kulomaa, Markku S

    2002-01-01

    Chicken avidin and bacterial streptavidin are proteins familiar from their use in various (strept)avidin-biotin technological applications. Avidin binds the vitamin biotin with the highest affinity known for non-covalent interactions found in nature. The gene encoding avidin (AVD) has homologues in chicken, named avidin-related genes (AVRs). In the present study we used the AVR genes to produce recombinant AVR proteins (AVRs 1, 2, 3, 4/5, 6 and 7) in insect cell cultures and characterized their biotin-binding affinity and biochemical properties. Amino acid sequence analysis and molecular modelling were also used to predict and explain the properties of the AVRs. We found that the AVR proteins are very similar to avidin, both structurally and functionally. Despite the numerous amino acid substitutions in the subunit interface regions, the AVRs form extremely stable tetramers similar to those of avidin. Differences were found in some physico-chemical properties of the AVRs as compared with avidin, including lowered pI, increased glycosylation and, most notably, reversible biotin binding for two AVRs (AVR1 and AVR2). Molecular modelling showed how the replacement Lys(111)-->isoleucine in AVR2 alters the shape of the biotin-binding pocket and thus results in reversible binding. Both modelling and biochemical analyses showed that disulphide bonds can form and link monomers in AVR4/5, a property not found in avidin. These, together with the other properties of the AVRs described in the present paper, may offer advantages over avidin and streptavidin, making the AVRs applicable for improved avidin-biotin technological applications. PMID:11964162

  11. Pairing symmetries of several iron-based superconductor families and some similarities with cuprates and heavy-fermions

    Directory of Open Access Journals (Sweden)

    Das Tanmoy

    2012-03-01

    Full Text Available We show that, by using the unit-cell transformation between 1 Fe per unit cell to 2 Fe per unit cell, one can qualitatively understand the pairing symmetry of several families of iron-based superconductors. In iron-pnictides and iron-chalcogenides, the nodeless s±-pairing and the resulting magnetic resonance mode transform nicely between the two unit cells, while retaining all physical properties unchanged. However, when the electron-pocket disappears from the Fermi surface with complete doping in KFe2As2, we find that the unit-cell invariant requirement prohibits the occurrence of s±-pairing symmetry (caused by inter-hole-pocket nesting. However, the intra-pocket nesting is compatible here, which leads to a nodal d-wave pairing. The corresponding Fermi surface topology and the pairing symmetry are similar to Ce-based heavy-fermion superconductors. Furthermore, when the Fermi surface hosts only electron-pockets in KyFe2-xSe2, the inter-electron-pocket nesting induces a nodeless and isotropic d-wave pairing. This situation is analogous to the electron-doped cuprates, where the strong antiferromagnetic order creates similar disconnected electron-pocket Fermi surface, and hence nodeless d-wave pairing appears. The unit-cell transformation in KyFe2-xSe2 exhibits that the d-wave pairing breaks the translational symmetry of the 2 Fe unit cell, and thus cannot be realized unless a vacancy ordering forms to compensate for it. These results are consistent with the coexistence picture of a competing order and nodeless d-wave superconductivity in both cuprates and KyFe1.6Se2.

  12. IQGAP Proteins Reveal an Atypical Phosphoinositide (aPI) Binding Domain with a Pseudo C2 Domain Fold

    Energy Technology Data Exchange (ETDEWEB)

    Dixon, Miles J.; Gray, Alexander; Schenning, Martijn; Agacan, Mark; Tempel, Wolfram; Tong, Yufeng; Nedyalkova, Lyudmila; Park, Hee-Won; Leslie, Nicholas R.; van Aalten, Daan M.F.; Downes, C. Peter; Batty, Ian H. (Toronto); (Dundee)

    2012-10-16

    Class I phosphoinositide (PI) 3-kinases act through effector proteins whose 3-PI selectivity is mediated by a limited repertoire of structurally defined, lipid recognition domains. We describe here the lipid preferences and crystal structure of a new class of PI binding modules exemplified by select IQGAPs (IQ motif containing GTPase-activating proteins) known to coordinate cellular signaling events and cytoskeletal dynamics. This module is defined by a C-terminal 105-107 amino acid region of which IQGAP1 and -2, but not IQGAP3, binds preferentially to phosphatidylinositol 3,4,5-trisphosphate (PtdInsP3). The binding affinity for PtdInsP3, together with other, secondary target-recognition characteristics, are comparable with those of the pleckstrin homology domain of cytohesin-3 (general receptor for phosphoinositides 1), an established PtdInsP3 effector protein. Importantly, the IQGAP1 C-terminal domain and the cytohesin-3 pleckstrin homology domain, each tagged with enhanced green fluorescent protein, were both re-localized from the cytosol to the cell periphery following the activation of PI 3-kinase in Swiss 3T3 fibroblasts, consistent with their common, selective recognition of endogenous 3-PI(s). The crystal structure of the C-terminal IQGAP2 PI binding module reveals unexpected topological similarity to an integral fold of C2 domains, including a putative basic binding pocket. We propose that this module integrates select IQGAP proteins with PI 3-kinase signaling and constitutes a novel, atypical phosphoinositide binding domain that may represent the first of a larger group, each perhaps structurally unique but collectively dissimilar from the known PI recognition modules.

  13. Simulation of Major Histocompatibility Complex (MHC) structure and peptide loading into an MHC binding pocket with teachers'hands.

    Science.gov (United States)

    Sankian, Mojtaba

    2013-10-01

    Molecular understanding of three-dimensional (3D) peptide: MHC models require both basic knowledge of computational modeling and skilled visual perception, which are not possessed by all students. The present model aims to simulate MHC molecular structure with the hands and make a profound impression on the students. PMID:26989722

  14. A Phenylnorstatine Inhibitor Binding to HIV-1 Protease: Geometry, Protonation and Subsite-Pocket Interactions Analyzed at Atomic Resolution

    Czech Academy of Sciences Publication Activity Database

    Brynda, Jiří; Řezáčová, Pavlína; Fábry, Milan; Hořejší, Magdalena; Štouračová, Renata; Sedláček, Juraj; Souček, Milan; Hradilek, Martin; Lepšík, Martin; Konvalinka, Jan

    Praha : Czech and Slovak Crystallographic Association, 2004 - (Kužel, R.; Hašek, J.; Fiala, J.; Weiss, Z.), s. 62 ISSN 1211-5894. - (Bulletin of the Czech and Slovak Crystallographic Association.. 11). [Meeting of the Czech and Slovak structural biologists /3./. Nové hrady (CZ), 11.03.2004-13.03.2004] R&D Projects: GA MŠk OE67/1 Institutional research plan: CEZ:AV0Z5052915 Keywords : inhibitor * HIV protease * atomic resolution Subject RIV: CE - Biochemistry

  15. A Phenylnorstatine Inhibitor Binding to HIV-1 Protease: Geometry, Protonation, and Subsite-Pocket Interactions Analyzed at Atomic Resolution

    Czech Academy of Sciences Publication Activity Database

    Brynda, Jiří; Řezáčová, Pavlína; Fábry, Milan; Hořejší, Magdalena; Štouračová, Renata; Sedláček, Juraj; Souček, Milan; Hradilek, Martin; Lepšík, Martin; Konvalinka, Jan

    2004-01-01

    Roč. 47, č. 8 (2004), s. 2030-2036. ISSN 0022-2623 Grant ostatní: V.program EU(XE) QLRI-2000-02360 Institutional research plan: CEZ:AV0Z5052915 Keywords : inhibitor * HIV protease * atomic resolution Subject RIV: CE - Biochemistry Impact factor: 5.076, year: 2004

  16. Design, synthesis and anti-HIV evaluation of novel diarylpyridine derivatives targeting the entrance channel of NNRTI binding pocket.

    Science.gov (United States)

    Yang, Jiapei; Chen, Wenmin; Kang, Dongwei; Lu, Xueyi; Li, Xiao; Liu, Zhaoqiang; Huang, Boshi; Daelemans, Dirk; Pannecouque, Christophe; De Clercq, Erik; Zhan, Peng; Liu, Xinyong

    2016-02-15

    The development of novel NNRTIs with activity against variants of HIV-1RT is crucial for overcoming treatment failure. In the present study, a series of novel 6-substituted diarylpyridine derivatives targeting the entrance channel of the NNIBP of RT were designed through a molecular hybridization strategy. Encouragingly, these new diarylpyridine derivatives were found to be active against wild-type (WT) HIV-1 with an EC50 values ranging from 0.035 μM to 1.99 μM. Nearly half of them exhibited more potent inhibitory activities in cellular assays than the control drug nevirapine (NVP). Notably, three most promising compounds If (EC50 = 35 nM), Ia (EC50 = 43 nM) and IIa (EC50 = 41 nM) showed high potency against WT and were comparable to the reference drug delavirdine (DLV) (EC50 = 33 nM). Moreover, compounds Ib, IIb and IIh displayed effective activity against the most common clinically observed single and double-mutated HIV-1 strains in micromolar concentrations. In particular, the inhibition of IIb against the K103N mutation (EC50 = 49 nM), which confers resistance to a wide variety of NNRTIs, was about 140 times more effective than NVP (EC50 = 6.78 μM), 50 times more than DLV (EC50 = 2.48 μM) and about 3 times more than EFV (EC50 = 0.12 μM), indicating that the newly designed compounds have great potential to be further developed as new anti-HIV-1 agents. Preliminary structure-activity relationships (SARs) and molecular modeling of the new diarylpyridine derivatives were discussed in detail. PMID:26802545

  17. Crystallographic analysis reveals the structural basis of the high-affinity binding of iophenoxic acid to human serum albumin

    Directory of Open Access Journals (Sweden)

    Chung Chun-wa

    2011-04-01

    Full Text Available Abstract Background Iophenoxic acid is an iodinated radiocontrast agent that was withdrawn from clinical use because of its exceptionally long half-life in the body, which was due in part to its high-affinity binding to human serum albumin (HSA. It was replaced by Iopanoic acid, which has an amino rather than a hydroxyl group at position 3 on the iodinated benzyl ring and, as a result, binds to albumin with lower affinity and is excreted more rapidly from the body. To understand how iophenoxic acid binds so tightly to albumin, we wanted to examine the structural basis of its interaction with HSA. Results We have determined the co-crystal structure of HSA in complex with iophenoxic acid at 2.75 Å resolution, revealing a total of four binding sites, two of which - in drugs sites 1 and 2 on the protein - are likely to be occupied at clinical doses. High-affinity binding of iophenoxic acid occurs at drug site 1. The structure reveals that polar and apolar groups on the compound are involved in its interactions with drug site 1. In particular, the 3-hydroxyl group makes three hydrogen bonds with the side-chains of Tyr 150 and Arg 257. The mode of binding to drug site 2 is similar except for the absence of a binding partner for the hydroxyl group on the benzyl ring of the compound. Conclusions The HSA-iophenoxic acid structure indicates that high-affinity binding to drug site 1 is likely to be due to extensive desolvation of the compound, coupled with the ability of the binding pocket to provide a full set of salt-bridging or hydrogen bonding partners for its polar groups. Consistent with this interpretation, the structure also suggests that the lower-affinity binding of iopanoic acid arises because replacement of the 3-hydroxyl by an amino group eliminates hydrogen bonding to Arg 257. This finding underscores the importance of polar interactions in high-affinity binding to albumin.

  18. Reconstitution of a surface transferrin binding complex in insect form Trypanosoma brucei.

    OpenAIRE

    Ligtenberg, M.J.; Bitter, W.; Kieft, R.; Steverding, D; Janssen, H.; Calafat, J.; Borst, P

    1994-01-01

    In the bloodstream of the mammalian host, Trypanosoma brucei takes up host transferrin by means of a high-affinity uptake system, presumably a transferrin receptor. Transferrin-binding activity is seen in the flagellar pocket and is absent in insect form trypanosomes. By transfection we have reconstituted a transferrin-binding complex in insect form trypanosomes. Formation of this complex requires the products of two genes that are part of a variant surface glycoprotein expression site, expre...

  19. Apolipoprotein M binds oxidized phospholipids and increases the antioxidant effect of HDL

    DEFF Research Database (Denmark)

    Elsøe, Sara; Ahnström, Josefin; Christoffersen, Christina;

    2012-01-01

    Oxidation of LDL plays a key role in the development of atherosclerosis. HDL may, in part, protect against atherosclerosis by inhibiting LDL oxidation. Overexpression of HDL-associated apolipoprotein M (apoM) protects mice against atherosclerosis through a not yet clarified mechanism. Being a lip...... lipocalin, apoM contains a binding pocket for small lipophilic molecules. Here, we report that apoM likely serves as an antioxidant in HDL by binding oxidized phospholipids, thus enhancing the antioxidant potential of HDL....

  20. Ligand binding and micro-switches in 7TM receptor structures

    DEFF Research Database (Denmark)

    Nygaard, Rie; Frimurer, Thomas M; Holst, Birgitte; Rosenkilde, Mette M; Schwartz, Thue W

    2009-01-01

    The past couple of years have seen several novel X-ray structures of 7 transmembrane (7TM) receptors in complex with antagonists and even with a peptide fragment of a G protein. These structures demonstrate that the main ligand-binding pocket in 7TM receptors is like a funnel with a partial 'lid...... domains (i.e. especially TM-VI), which performs the large, global toggle switch movements connecting ligand binding with intracellular signaling....

  1. Structural proof of a dimeric positive modulator bridging two identical AMPA receptor-binding sites

    DEFF Research Database (Denmark)

    Kaae, Birgitte Høiriis; Harpsøe, Kasper; Kastrup, Jette Sandholm Jensen;

    2007-01-01

    have dramatically increased potencies, more than three orders of magnitude higher than the corresponding monomers. Dimer (R,R)-2a was cocrystallized with the GluR2-S1S2J construct, and an X-ray crystallographic analysis showed (R,R)-2a to bridge two identical binding pockets on two neighboring GluR2...... subunits. Thus, this is biostructural evidence of a homomeric dimer bridging two identical receptor-binding sites....

  2. Multivariate Time Series Similarity Searching

    OpenAIRE

    Jimin Wang; Yuelong Zhu; Shijin Li; Dingsheng Wan; Pengcheng Zhang

    2014-01-01

    Multivariate time series (MTS) datasets are very common in various financial, multimedia, and hydrological fields. In this paper, a dimension-combination method is proposed to search similar sequences for MTS. Firstly, the similarity of single-dimension series is calculated; then the overall similarity of the MTS is obtained by synthesizing each of the single-dimension similarity based on weighted BORDA voting method. The dimension-combination method could use the existing similarity searchin...

  3. The use of pocket-size imaging devices: a position statement of the European Association of Echocardiography.

    Science.gov (United States)

    Sicari, Rosa; Galderisi, Maurizio; Voigt, Jens-Uwe; Habib, Gilbert; Zamorano, Jose L; Lancellotti, Patrizio; Badano, Luigi P

    2011-02-01

    Pocket-size imaging devices are a completely new type of echo machines which have recently reached the market. They are very cheap, smartphone-size hand-held echo machines with limited technical capabilities. The aim of this European Association of Echocardiography (EAE) position paper is to provide recommendations on the use of pocket-size imaging devices in the clinical arena by profiling the educational needs of potential users other than cardiologists experts in echo. EAE recommendations about pocket-size imaging devices can be summarized in: (1) pocket-size imaging devices do not provide a complete diagnostic echocardiographic examination. The range of indications for their use is therefore limited. (2) Imaging assessment with pocket-size imaging devices should be reported as part of the physical examination of the patient. Image data should be stored according to the applicable national rules for technical examinations. (3) With the exception of cardiologists who are certified for transthoracic echocardiography according to national legislation, specific training and certification is recommended for all users. The certification should be limited to the clinical questions that can potentially be answered by pocket-size devices. (4) The patient has to be informed that an examination with the current generation of pocket-size imaging devices does not replace a complete echocardiogram. PMID:21216764

  4. Collagen binding to Staphylococcus aureus

    International Nuclear Information System (INIS)

    Staphylococcus aureus can bind soluble collagen in a specific, saturable manner. We have previously shown that some variability exists in the degree of collagen binding between different strains of heat-killed, formaldehyde-fixed S. aureus which are commercially available as immunologic reagents. The present study demonstrates that live S. aureus of the Cowan 1 strain binds amounts of collagen per organism equivalent to those demonstrated previously in heat-killed, formaldehyde-fixed bacteria but has an affinity over 100 times greater, with Kd values of 9.7 X 10(-11) M and 4.3 X 10(-8) M for live and heat-killed organisms, respectively. Studies were also carried out with S. aureus killed by ionizing radiation, since this method of killing the organism seemed less likely to alter the binding moieties on the surface than did heat killing. Bacteria killed by exposure to gamma radiation bound collagen in a manner essentially indistinguishable from that of live organisms. Binding of collagen to irradiated cells of the Cowan 1 strain was rapid, with equilibrium reached by 30 min at 22 degrees C, and was fully reversible. The binding was not inhibited by fibronectin, fibrinogen, C1q, or immunoglobulin G, suggesting a binding site for collagen distinct from those for these proteins. Collagen binding was virtually eliminated in trypsin-treated organisms, indicating that the binding site has a protein component. Of four strains examined, Cowan 1 and S. aureus ATCC 25923 showed saturable, specific binding, while strains Woods and S4 showed a complete lack of binding. These results suggest that some strains of S. aureus contain high-affinity binding sites for collagen. While the number of binding sites per bacterium varied sixfold in the two collagen-binding strains, the apparent affinity was similar

  5. Modulated Degradation of Transient Electronic Devices through Multilayer Silk Fibroin Pockets.

    Science.gov (United States)

    Brenckle, Mark A; Cheng, Huanyu; Hwang, Sukwon; Tao, Hu; Paquette, Mark; Kaplan, David L; Rogers, John A; Huang, Yonggang; Omenetto, Fiorenzo G

    2015-09-16

    The recent introduction of transient, bioresorbable electronics into the field of electronic device design offers promise for the areas of medical implants and environmental monitors, where programmed loss of function and environmental resorption are advantageous characteristics. Materials challenges remain, however, in protecting the labile device components from degradation at faster than desirable rates. Here we introduce an indirect passivation strategy for transient electronic devices that consists of encapsulation in multiple air pockets fabricated from silk fibroin. This approach is investigated through the properties of silk as a diffusional barrier to water penetration, coupled with the degradation of magnesium-based devices in humid air. Finally, silk pockets are demonstrated to be useful for controlled modulation of device lifetime. This approach may provide additional future opportunities for silk utility due to the low immunogenicity of the material and its ability to stabilize labile biotherapeutic dopants. PMID:26305434

  6. Pars tensa retraction pockets in children: treatment by excision and ventilation tube insertion.

    Science.gov (United States)

    Srinivasan, V; Banhegyi, G; O'Sullivan, G; Sherman, I W

    2000-08-01

    Tympanic membrane retraction pockets involving the pars tensa are not uncommon in clinical practice. Recurrent infections, ossicular erosion and cholesteatoma are the recognized sequelae. The management options include surveillance, medical treatment and surgery. The surgical procedures range from grommet insertion to extensive tympanoplasty procedures. We report our experience with simple excision and grommet insertion, performed in 31 ears in 26 patients as day cases. The follow-up ranged from 8 to 34 months with a mean of 16 months. The procedure was successful in 23 ears (success rate of 74%). Recurrence of retraction occurred in seven ears and in one ear there was a persistent perforation. Age, previous grommet insertion and severity of retraction did not have a statistically significant influence on the final outcome. We conclude that excision and grommet insertion is a simple, safe and efficient procedure for the management of tympanic membrane retraction pockets and can be considered in preference to extensive tympanoplasty. PMID:10971530

  7. Characterization of vertical strain silicon MOSFET incorporating dielectric pocket (SDP-VMOSFET)

    Energy Technology Data Exchange (ETDEWEB)

    Napiah, Z. A. F. M., E-mail: zulatfyi@utem.edu.my, E-mail: nazirah6969@gmail.com, E-mail: azlishah@utem.edu.my, E-mail: idzdihar@utem.edu.my, E-mail: faiz.arith@utem.edu.my, E-mail: yashidar@yahoo.com, E-mail: sitinabilahtaib@gmail.com; Makhtar, N., E-mail: zulatfyi@utem.edu.my, E-mail: nazirah6969@gmail.com, E-mail: azlishah@utem.edu.my, E-mail: idzdihar@utem.edu.my, E-mail: faiz.arith@utem.edu.my, E-mail: yashidar@yahoo.com, E-mail: sitinabilahtaib@gmail.com; Othman, M. A., E-mail: zulatfyi@utem.edu.my, E-mail: nazirah6969@gmail.com, E-mail: azlishah@utem.edu.my, E-mail: idzdihar@utem.edu.my, E-mail: faiz.arith@utem.edu.my, E-mail: yashidar@yahoo.com, E-mail: sitinabilahtaib@gmail.com; Idris, M. I., E-mail: zulatfyi@utem.edu.my, E-mail: nazirah6969@gmail.com, E-mail: azlishah@utem.edu.my, E-mail: idzdihar@utem.edu.my, E-mail: faiz.arith@utem.edu.my, E-mail: yashidar@yahoo.com, E-mail: sitinabilahtaib@gmail.com; Arith, F., E-mail: zulatfyi@utem.edu.my, E-mail: nazirah6969@gmail.com, E-mail: azlishah@utem.edu.my, E-mail: idzdihar@utem.edu.my, E-mail: faiz.arith@utem.edu.my, E-mail: yashidar@yahoo.com, E-mail: sitinabilahtaib@gmail.com; Yasin, N. Y. M., E-mail: zulatfyi@utem.edu.my, E-mail: nazirah6969@gmail.com, E-mail: azlishah@utem.edu.my, E-mail: idzdihar@utem.edu.my, E-mail: faiz.arith@utem.edu.my, E-mail: yashidar@yahoo.com, E-mail: sitinabilahtaib@gmail.com; Taib, S. N., E-mail: zulatfyi@utem.edu.my, E-mail: nazirah6969@gmail.com, E-mail: azlishah@utem.edu.my, E-mail: idzdihar@utem.edu.my, E-mail: faiz.arith@utem.edu.my, E-mail: yashidar@yahoo.com, E-mail: sitinabilahtaib@gmail.com [Centre for Telecommunication Research and Innovation (CeTRI), Faculty of Electronic and Computer Engineering, Universiti Teknikal Malaysia Melaka, Hang Tuah Jaya, 76100 Durian Tunggal, Melaka (Malaysia)

    2014-02-24

    The vertical Metal-Oxide-Semiconductor Field-Effect-Transistor (MOSFET) leads to a double channel width that can increase the packaging density. The strained silicon MOSFET was introduced to modify the carrier transport properties of silicon in order to enhance transport of both electrons and holes within strained layer. Dielectric pocket was act to control encroachment of the drain doping into the channel and reduce short channel effects (SCE). SDP-VMOSFET which was a combination of those advantages was proposed to overcome the SCE in term of leakage current, threshold voltage roll-off also Drain Induce Barrier Lowering (DIBL). As a result, SDP-VMOSFET produces a better threshold voltage and DIBL compared to related structures. Meanwhile, it gives slightly increased for leakage current compared to Vertical MOSFET Incorporating Dielectric Pocket. The characteristics of the SDP-VMOSFET are analyzed in order to optimize the performance of the device and leading to the next generation of IC technology.

  8. Mechanistic differences between methanol and dimethyl ether carbonylation in side pockets and large channels of mordenite.

    Science.gov (United States)

    Boronat, Mercedes; Martínez, Cristina; Corma, Avelino

    2011-02-21

    The activity and selectivity towards carbonylation presented by Brønsted acid sites located inside the 8MR pockets or in the main 12MR channels of mordenite is studied by means of quantum-chemical calculations, and the mechanistic differences between methanol and DME carbonylation are investigated. The selectivity towards carbonylation is higher inside the 8MR pockets, where the competitive formation of DME and hydrocarbons that finally leads to catalyst deactivation is sterically impeded. Moreover, inclusion of dispersion interactions in the calculations leads to agreement between the calculated activation barriers for the rate determining step and the experimentally observed higher reactivity of methoxy groups located inside the 8MR channels. PMID:21249237

  9. Characterization of vertical strain silicon MOSFET incorporating dielectric pocket (SDP-VMOSFET)

    International Nuclear Information System (INIS)

    The vertical Metal-Oxide-Semiconductor Field-Effect-Transistor (MOSFET) leads to a double channel width that can increase the packaging density. The strained silicon MOSFET was introduced to modify the carrier transport properties of silicon in order to enhance transport of both electrons and holes within strained layer. Dielectric pocket was act to control encroachment of the drain doping into the channel and reduce short channel effects (SCE). SDP-VMOSFET which was a combination of those advantages was proposed to overcome the SCE in term of leakage current, threshold voltage roll-off also Drain Induce Barrier Lowering (DIBL). As a result, SDP-VMOSFET produces a better threshold voltage and DIBL compared to related structures. Meanwhile, it gives slightly increased for leakage current compared to Vertical MOSFET Incorporating Dielectric Pocket. The characteristics of the SDP-VMOSFET are analyzed in order to optimize the performance of the device and leading to the next generation of IC technology

  10. A mollusk retinoic acid receptor (RAR) ortholog sheds light on the evolution of ligand binding.

    Science.gov (United States)

    Gutierrez-Mazariegos, Juliana; Nadendla, Eswar Kumar; Lima, Daniela; Pierzchalski, Keely; Jones, Jace W; Kane, Maureen; Nishikawa, Jun-Ichi; Hiromori, Youhei; Nakanishi, Tsuyoshi; Santos, Miguel M; Castro, L Filipe C; Bourguet, William; Schubert, Michael; Laudet, Vincent

    2014-11-01

    Nuclear receptors are transcription factors that regulate networks of target genes in response to small molecules. There is a strong bias in our knowledge of these receptors because they were mainly characterized in classical model organisms, mostly vertebrates. Therefore, the evolutionary origins of specific ligand-receptor couples still remain elusive. Here we present the identification and characterization of a retinoic acid receptor (RAR) from the mollusk Nucella lapillus (NlRAR). We show that this receptor specifically binds to DNA response elements organized in direct repeats as a heterodimer with retinoid X receptor. Surprisingly, we also find that NlRAR does not bind all-trans retinoic acid or any other retinoid we tested. Furthermore, NlRAR is unable to activate the transcription of reporter genes in response to stimulation by retinoids and to recruit coactivators in the presence of these compounds. Three-dimensional modeling of the ligand-binding domain of NlRAR reveals an overall structure that is similar to vertebrate RARs. However, in the ligand-binding pocket (LBP) of the mollusk receptor, the alteration of several residues interacting with the ligand has apparently led to an overall decrease in the strength of the interaction with the ligand. Accordingly, mutations of NlRAR at key positions within the LBP generate receptors that are responsive to retinoids. Altogether our data suggest that, in mollusks, RAR has lost its affinity for all-trans retinoic acid, highlighting the evolutionary plasticity of its LBP. When put in an evolutionary context, our results reveal new structural and functional features of nuclear receptors validated by millions of years of evolution that were impossible to reveal in model organisms. PMID:25116705

  11. Structural Analysis of Papain-Like NlpC/P60 Superfamily Enzymes with a Circularly Permuted Topology Reveals Potential Lipid Binding Sites

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Qingping; Rawlings, Neil D.; Chiu, Hsiu-Ju; Jaroszewski, Lukasz; Klock, Heath E.; Knuth, Mark W.; Miller, Mitchell D.; Elsliger, Marc-Andre; Deacon, Ashley M.; Godzik, Adam; Lesley, Scott A.; Wilson, Ian A. (SG); (Wellcome)

    2012-07-11

    NlpC/P60 superfamily papain-like enzymes play important roles in all kingdoms of life. Two members of this superfamily, LRAT-like and YaeF/YiiX-like families, were predicted to contain a catalytic domain that is circularly permuted such that the catalytic cysteine is located near the C-terminus, instead of at the N-terminus. These permuted enzymes are widespread in virus, pathogenic bacteria, and eukaryotes. We determined the crystal structure of a member of the YaeF/YiiX-like family from Bacillus cereus in complex with lysine. The structure, which adopts a ligand-induced, 'closed' conformation, confirms the circular permutation of catalytic residues. A comparative analysis of other related protein structures within the NlpC/P60 superfamily is presented. Permutated NlpC/P60 enzymes contain a similar conserved core and arrangement of catalytic residues, including a Cys/His-containing triad and an additional conserved tyrosine. More surprisingly, permuted enzymes have a hydrophobic S1 binding pocket that is distinct from previously characterized enzymes in the family, indicative of novel substrate specificity. Further analysis of a structural homolog, YiiX (PDB 2if6) identified a fatty acid in the conserved hydrophobic pocket, thus providing additional insights into possible function of these novel enzymes.

  12. Reimbursement for out of Pocket Expenses for Service Users and Carers

    OpenAIRE

    Public Health Agency

    2012-01-01

    The PHA, through the Regional HSC Personal and Public Involvement Forum, have led on the development of an agreed regional policy to ensure that services users and carers are not out of pocket when involved in helping us to plan, deliver, review and evaluate HSC services. Staff are asked to familiarise themselves with the policy and apply it when involving services users and carers in their work.���

  13. Cytological analysis of the periodontal pocket in patients with aggressive periodontitis and chronic periodontitis

    OpenAIRE

    E Castro Cecilia; A Koss Myriam; E López María

    2014-01-01

    Background: Oral exfoliative cytology includes the study and interpretation of the features cells exfoliated from the oral mucosa. The aim of this study was to analyze cytological changes in the periodontal pocket of patients with different clinical stages of aggressive periodontitis (AP) and chronic periodontitis (CP). Materials and Methods: Patients aged 24-54 years, of whom 41 were diagnosed with AP, 40 with CP, sub-classified as mild, moderate and severe periodontitis, and 40 healthy indi...

  14. GCE and solar S-process abundances. Dependence on the 13C-pocket structure

    International Nuclear Information System (INIS)

    We study the s-process abundances (A>90) at the epoch of the formation of the solar-system as the outcome of nucleosynthesis occurring in AGB stars of various initial masses and metallicities. AGB yields are computed with an updated neutron capture network and updated initial solar abundances. We use a Galactic Chemical Evolution (GCE) code based on, slightly modified accounting for the new determination of the age of the Universe (13.8 Gyr [3]) and solar abundances by [4]. At present, one of the most problematic issues of AGB stellar models is the formation of the 13C-pocket, where the major neutron source of the s-process (the 13C(α, n)16O reaction) burns radiatively. Indeed, the internal structure of the 13C-pocket may depend on the stellar characteristic (e.g., AGB initial mass and metallicity), and on the interplay between physical mechanisms that may compete in the star itself (e.g., rotation, magnetic fields, gravity waves). Because of the present uncertainties, we adopt in our AGB models a free parametrization of the 13C-pocket as has been done by [1]: this approximation allow us to investigate the impact of different internal structures of the 13C-pocket on the GCE s-distribution. We discuss our results in the light of the most recent studies.We follow the chemical evolution of several elements (e.g., α, Zr, Ba, Eu) along the stellar age and metallicity, comparing our results with the most update spectroscopic observations (e.g., [11,12]). (author)

  15. Local Histogram Matching for Efficient Optical Flow Computation Applied to Velocity Estimation on Pocket Drones

    OpenAIRE

    McGuire, Kimberly; de Croon, Guido; de Wagter, Christophe; Remes, Bart; Tuyls, Karl; Kappen, Hilbert

    2016-01-01

    Autonomous flight of pocket drones is challenging due to the severe limitations on on-board energy, sensing, and processing power. However, tiny drones have great potential as their small size allows maneuvering through narrow spaces while their small weight provides significant safety advantages. This paper presents a computationally efficient algorithm for determining optical flow, which can be run on an STM32F4 microprocessor (168 MHz) of a 4 gram stereo-camera. The optical flow algorithm ...

  16. Young Adult Insurance Coverage And Out-Of-Pocket Spending: Long-Term Patterns.

    Science.gov (United States)

    Berk, Marc L; Fang, Zhengyi

    2016-04-01

    The Affordable Care Act appears to have improved health insurance coverage for young adults (ages 18-30). But data from twenty national surveys conducted between 1977 and 2013 paint a more complex picture, showing coverage rates lower in 2013 than they were thirty-six years earlier. Racial and ethnic disparities in coverage have declined recently, while out-of-pocket expenditures remain low for most young adults. PMID:27008855

  17. New pockets in dengue virus 2 surface identified by molecular dynamics simulation

    OpenAIRE

    Fuzo, Carlos A.; Degrève, Léo

    2012-01-01

    One of the factors limiting the search of new compounds based on the structure of target proteins involved in diseases is the limited amount of target structural information. Great advances in the search for lead compounds could be achieved to find new cavities in protein structures that are generated using well established computational chemistry tools. In the case of dengue, the discovery of pockets in the crystallographic structure of the E protein has contributed to the search for lead co...

  18. Focused Cardiac Ultrasound Using a Pocket-Size Device in the Emergency Room

    OpenAIRE

    Mancuso, Frederico José Neves; Siqueira, Vicente Nicoliello; Moisés, Valdir Ambrósio; Gois, Aécio Flavio Teixeira; de Paola, Angelo Amato Vincenzo; Carvalho, Antonio Carlos Camargo; Campos, Orlando

    2014-01-01

    Background Cardiovascular urgencies are frequent reasons for seeking medical care. Prompt and accurate medical diagnosis is critical to reduce the morbidity and mortality of these conditions. Objective To evaluate the use of a pocket-size echocardiography in addition to clinical history and physical exam in a tertiary medical emergency care. Methods One hundred adult patients without known cardiac or lung diseases who sought emergency care with cardiac complaints were included. Patients with ...

  19. Characterization of polymer release from the flagellar pocket of Leishmania mexicana promastigotes

    OpenAIRE

    1994-01-01

    Trypanosomatids contain a unique compartment, the flagellar pocket, formed by an invagination of the plasma membrane at the base of the flagellum, which is considered to be the sole cellular site for endocytosis and exocytosis of macromolecules. The culture supernatant of Leishmania mexicana promastigotes, the insect stage of this protozoan parasite, contains two types of polymers: a filamentous acid phosphatase (sAP) composed of a 100-kD phosphoglycoprotein with non- covalently associated pr...

  20. Morphological adaptations for digging and climate-impacted soil properties define pocket gopher (Thomomys spp. distributions.

    Directory of Open Access Journals (Sweden)

    Ariel E Marcy

    Full Text Available Species ranges are mediated by physiology, environmental factors, and competition with other organisms. The allopatric distribution of five species of northern Californian pocket gophers (Thomomys spp. is hypothesized to result from competitive exclusion. The five species in this environmentally heterogeneous region separate into two subgenera, Thomomys or Megascapheus, which have divergent digging styles. While all pocket gophers dig with their claws, the tooth-digging adaptations of subgenus Megascapheus allow access to harder soils and climate-protected depths. In a Northern Californian locality, replacement of subgenus Thomomys with subgenus Megascapheus occurred gradually during the Pleistocene-Holocene transition. Concurrent climate change over this transition suggests that environmental factors--in addition to soil--define pocket gopher distributional limits. Here we show 1 that all pocket gophers occupy the subset of less energetically costly soils and 2 that subgenera sort by percent soil clay, bulk density, and shrink-swell capacity (a mineralogical attribute. While clay and bulk density (without major perturbations stay constant over decades to millennia, low precipitation and high temperatures can cause shrink-swell clays to crack and harden within days. The strong yet underappreciated interaction between soil and moisture on the distribution of vertebrates is rarely considered when projecting species responses to climatic change. Furthermore, increased precipitation alters the weathering processes that create shrink-swell minerals. Two projected outcomes of ongoing climate change--higher temperatures and precipitation--will dramatically impact hardness of soil with shrink-swell minerals. Current climate models do not include factors controlling soil hardness, despite its impact on all organisms that depend on a stable soil structure.

  1. Multiple Fermi pockets revealed by Shubnikov-de Haas oscillations in WTe2

    OpenAIRE

    Xiang, Fei-Xiang; Veldhorst, Menno; Dou, Shi-Xue; Wang, Xiao-lin

    2015-01-01

    We use magneto-transport measurements to investigate the electronic structure of WTe2 single crystals. A non-saturating and parabolic magnetoresistance is observed in the temperature range between 2.5 to 200 K and magnetic fields up to 8 T. Shubnikov - de Haas oscillations with beating patterns are observed. The fast Fourier transform of the SdH oscillations reveals three oscillation frequencies, corresponding to three pairs of Fermi pockets with comparable effective masses , m* ~ 0.31 me. By...

  2. Triple Point Collision and Origin of Unburned Gas Pockets in Irregular Detonations

    OpenAIRE

    Mahmoudi, Yasser; Mazaheri, Kiumars

    2014-01-01

    The turbulent structure of an irregular detonation is studied through very high resolution numerical simulations of 600 points per half reaction length. The aim is to explore the nature of the transverse waves during the collision and reflection processes of the triple point with the channel walls. Consequently the formation and consumption mechanism of unreacted gas pockets is studied. Results show that as the triple point collides with the wall, the transverse shock interacts with the unrea...

  3. Out-of-pocket health spending by poor and near-poor elderly Medicare beneficiaries.

    OpenAIRE

    Gross, D. J.; Alecxih, L; Gibson, M J; Corea, J; Caplan, C; Brangan, N

    1999-01-01

    OBJECTIVE: To estimate out-of-pocket health care spending by lower-income Medicare beneficiaries, and to examine spending variations between those who receive Medicaid assistance and those who do not receive such aid. DATA SOURCES AND COLLECTION: 1993 Medicare Current Beneficiary Survey (MCBS) Cost and Use files, supplemented with data from the Bureau of the Census (Current Population Survey); the Congressional Budget Office; the Health Care Financing Administration, Office of the Actuary (Na...

  4. The influence of Injection Pockets on the Performance of Tilting-Pad Thrust Bearings: Part I - Theory

    DEFF Research Database (Denmark)

    Heinrichson, Niels; Santos, Ilmar; Fuerst, Axel

    This is Part I of a two-part series of papers describing the effects of high pressure injection pockets on the operating conditions of tilting-pad thrust bearings. A numerical model based on the Reynolds equation is developed extending the three dimensional thermo-elasto-hydrodynamic (TEHD......) analysis of tilting-pad thrust bearings to include the effects of high pressure injection and recesses in the bearing pad. The model is applied to the analysis of an existing bearing of large dimensions and the influence of the pocket is analyzed. It is shown that a shallow pocket positively influences the...

  5. Development testing of a pocket-type, hydrostatic rotary end face seal in high-pressure water

    International Nuclear Information System (INIS)

    Experimental work to study the effects of balance ratio, seal face divergency, shaft speed and number of pockets on leakage and tilt stability, for a 9.5 cm pocket-type, hydrostatic rotary end face seal in high-pressure water, is described and discussed. It is shown that leakage and tilt stability, for a given pressure, both depend primarily on balance ratio and parallelity of the sealing gap. It is also shown that seal face separation prevails even if the sealing gap is slightly divergent. For the seal, the data indicate that at least six pockets are required to obtain close to maximum tilt stability

  6. Health care consumers’ opinions on different variants of out-of-pocket payments. A cross-sectional questionnaire study (2013).

    OpenAIRE

    Reitsma, M.; J. De Jong

    2014-01-01

    Background: Health care expenditures are rising faster than the resources in many countries. One of the tools to reduce this expenditures is by introducing out-of-pocket payments. With these payments insured have to pay (part of) the costs of health care themselves. One of the aims of out-of pocket payments is that it leads to less health care use. The assumption is that out-of-pocket-payments lead to a higher cost consciousness which is assumed to lead to cost conscious behavior and herewith...

  7. Cytological analysis of the periodontal pocket in patients with aggressive periodontitis and chronic periodontitis

    Directory of Open Access Journals (Sweden)

    E Castro Cecilia

    2014-01-01

    Full Text Available Background: Oral exfoliative cytology includes the study and interpretation of the features cells exfoliated from the oral mucosa. The aim of this study was to analyze cytological changes in the periodontal pocket of patients with different clinical stages of aggressive periodontitis (AP and chronic periodontitis (CP. Materials and Methods: Patients aged 24-54 years, of whom 41 were diagnosed with AP, 40 with CP, sub-classified as mild, moderate and severe periodontitis, and 40 healthy individuals who were the control group. Samples of the epithelium of the periodontal pocket were taken for the cytological study. Results: Superficial and intermediate cell values were significantly greater in patients with AP than in patients with CP or the control group. Histiocyte number was higher in patients with CP than in those with AP, and differed significantly in both types of periodontitis compared to the control group. There were significant differences in polymorphonuclear neutrophil leukocytes when both types of periodontitis were compared to the control group. Microbial flora was statistically higher in patients with CP, and there were differences between patients with periodontitis and the control group. Conclusions: The cytological study demonstrated that patients with AP had greater tissue damage, shown by the increase in intermediate and superficial cells of the epithelium of the periodontal pocket compared to the group of healthy subjects and to a lesser extent, to patients with CP. Only superficial cells made it possible to differentiate the sub-stages of the disease.

  8. Multiple Fermi pockets revealed by Shubnikov-de Haas oscillations in WTe2

    Science.gov (United States)

    Xiang, Fei-Xiang; Veldhorst, Menno; Dou, Shi-Xue; Wang, Xiao-Lin

    2015-11-01

    The recently discovered non-saturating and parabolic magnetoresistance and the pressure-induced superconductivity at low temperature in WTe2 imply its rich electronic structure and possible practical applications. Here we use magnetotransport measurements to investigate the electronic structure of WTe2 single crystals. A non-saturating and parabolic magnetoresistance is observed from low temperature to high temperature up to 200 K with magnetic fields up to 8 T. Shubnikov-de Haas (SdH) oscillations with beating patterns are observed, the fast Fourier transform of which reveals three oscillation frequencies, corresponding to three pairs of Fermi pockets with comparable effective masses, m* ∼ 0.31~me . By fitting the Hall resistivity, we infer that they can be attributed to one pair of electron pockets and two pairs of hole pockets, together with nearly perfect compensation of the electron-hole carrier concentration. These magnetotransport measurements reveal the complex electronic structure in WTe2, explaining the non-saturating magnetoresistance.

  9. Functional Similarity and Interpersonal Attraction.

    Science.gov (United States)

    Neimeyer, Greg J.; Neimeyer, Robert A.

    1981-01-01

    Students participated in dyadic disclosure exercises over a five-week period. Results indicated members of high functional similarity dyads evidenced greater attraction to one another than did members of low functional similarity dyads. "Friendship" pairs of male undergraduates displayed greater functional similarity than did "nominal" pairs from…

  10. Improving structural similarity based virtual screening using background knowledge

    OpenAIRE

    Girschick, Tobias; Puchbauer, Lucia; Kramer, Stefan

    2013-01-01

    Background Virtual screening in the form of similarity rankings is often applied in the early drug discovery process to rank and prioritize compounds from a database. This similarity ranking can be achieved with structural similarity measures. However, their general nature can lead to insufficient performance in some application cases. In this paper, we provide a link between ranking-based virtual screening and fragment-based data mining methods. The inclusion of binding-relevant background k...

  11. Health service use, out-of-pocket payments and catastrophic health expenditure among older people in India

    DEFF Research Database (Denmark)

    Brinda, Ethel Mary; Kowal, Paul; Attermann, Jørn;

    2015-01-01

    BACKGROUND: Healthcare financing through out-of-pocket payments and inequities in healthcare utilisation are common in low and middle income countries (LMICs). Given the dearth of pertinent studies on these issues among older people in LMICs, we investigated the determinants of health service use......, out-of-pocket and catastrophic health expenditures among older people in one LMIC, India. METHODS: We accessed data from a nationally representative, multistage sample of 2414 people aged 65 years and older from the WHO's Study on global Ageing and adult health in India. Sociodemographic...... regression models were used to assess the determinants of out-of-pocket and catastrophic health expenditures. RESULTS: Out-of-pocket health expenditures were higher among participants with disability and lower income. Diabetes, hypertension, chronic pulmonary disease, heart disease and tuberculosis increased...

  12. Dissecting functions of the retinoblastoma tumor suppressor and the related pocket proteins by integrating genetic, cell biology, and electrophoretic techniques

    DEFF Research Database (Denmark)

    Hansen, Klaus; Lukas, J; Holm, K;

    1999-01-01

    The members of the 'pocket protein' family, comprising the retinoblastoma tumor suppressor (pRB) and its relatives, p107 and p130, negatively regulate cell proliferation and modulate fundamental biological processes including embryonic development, differentiation, homeostatic tissue renewal, and...

  13. Residues accessible in the binding-site crevice of transmembrane helix 6 of the CB2 cannabinoid receptor.

    Science.gov (United States)

    Nebane, Ntsang M; Hurst, Dow P; Carrasquer, Carl A; Qiao, Zhuanhong; Reggio, Patricia H; Song, Zhao-Hui

    2008-12-30

    We have used the substituted-cysteine accessibility method (SCAM) to map the residues in the sixth membrane-spanning segment of the CB2 cannabinoid receptor that contribute to the surface of the water-accessible binding-site crevice. Using a background of the mutant C2.59S which is relatively insensitive to the methanethiosulfonate (MTS) reagents, we mutated to cysteine, one at a time, 34 consecutive residues in TMH6 of the CB2 receptor. These mutant receptors were then expressed in HEK293 cells. By incubating HEK293 cells stably transfected with CB2 receptors with the small, charged, hydrophilic, thiol-specific reagent methanethiosulfonate ethylammonium (MTSEA), [(3)H]CP55940 binding was significantly inhibited for six mutant receptors. All six of the mutants that reacted with MTSEA were protected from the reaction when pretreated with the cannabinoid agonist WIN55212-2, suggesting that MTSEA modification occurred within the binding crevice. Therefore, the side chains of the residues at these reactive loci (V6.51, L6.52, L6.54, M6.55, L6.59, and T6.62) are on the water-accessible surface of the binding-site crevice. These residues are extracellular to the TMH6 CWXP hinge motif. The pattern of accessibility is consistent with a alpha-helical conformation for this segment of TMH6. Molecular modeling studies performed in the context of the CB2 model show that V6.51, L6.52, L6.54, M6.55, L6.59, and T6.62 face into the CB2 binding pocket, further confirming our SCAM results. These results are similar to the accessibility patterns determined by SCAM studies of TMH6 in the opioid and dopamine D2 receptors. PMID:19053233

  14. Conformational and functional analysis of the lipid binding protein Ag-NPA-1 from the parasitic nematode Ascaridia galli.

    Science.gov (United States)

    Jordanova, Rositsa; Radoslavov, Georgi; Fischer, Peter; Liebau, Eva; Walter, Rolf D; Bankov, Ilia; Boteva, Raina

    2005-01-01

    Ag-NPA-1 (AgFABP), a 15 kDa lipid binding protein (LBP) from Ascaridia galli, is a member of the nematode polyprotein allergen/antigen (NPA) family. Spectroscopic analysis shows that Ag-NPA-1 is a highly ordered, alpha-helical protein and that ligand binding slightly increases the ordered secondary structure content. The conserved, single Trp residue (Trp17) and three Tyr residues determine the fluorescence properties of Ag-NPA-1. Analysis of the efficiency of the energy transfer between these chromophores shows a high degree of Tyr-Trp dipole-dipole coupling. Binding of fatty acids and retinol was accompanied by enhancement of the Trp emission, which allowed calculation of the affinity constants of the binary complexes. The distance between the single Trp of Ag-NPA-1 and the fluorescent fatty acid analogue 11-[(5-dimethylaminonaphthalene-1- sulfonyl)amino]undecanoic acid (DAUDA) from the protein binding site is 1.41 nm as estimated by fluorescence resonance energy transfer. A chemical modification of the Cys residues of Ag-NPA-1 (Cys66 and Cys122) with the thiol reactive probes 5-({[(2-iodoacetyl)amino]ethyl}amino) naphthalene-1-sulfonic acid (IAEDANS) and N,N'-dimethyl-N-(iodoacetyl)-N'-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)ethylenediamine (IANBD), followed by MALDI-TOF analysis showed that only Cys66 was labeled. The observed similar affinities for fatty acids of the modified and native Ag-NPA-1 suggest that Cys66 is not a part of the protein binding pocket but is located close to it. Ag-NPA-1 is one of the most abundant proteins in A. galli and it is distributed extracellularly mainly as shown by immunohistology and immunogold electron microscopy. This suggests that Ag-NPA-1 plays an important role in the transport of fatty acids and retinoids. PMID:15634342

  15. Use of an active fixation lead and a subpectoral pacemaker pocket may not avoid Twiddler′s syndrome

    Directory of Open Access Journals (Sweden)

    Floris E A Udink ten Cate

    2012-01-01

    Full Text Available Manipulation of a pacemaker with consequent malfunction of the device has been called Twiddler′s syndrome. Use of active-fixation leads and subpectoral pacemaker pockets has been considered to help in avoiding this problem. We describe a child in whom twiddling was not prevented despite implantation of a lumenless atrial lead and insertion of the pacemaker generator in a subpectoral pocket.

  16. Nuclear pockets and clefts in the lymphoid cell population of bone marrow and blood of children with acute lymphoblastic leukemia.

    OpenAIRE

    Schuurmans Stekhoven, J. H.; Holland, R.

    1986-01-01

    Ultrastructural investigation of the nuclei of the lymphoid cell population of bone marrow and blood of children with acute lymphoblastic leukemia regularly shows the presence of two types of nuclear pockets and nuclear clefts. The incidences of these nuclear features decrease significantly during cytostatic therapy. The pockets consist of either a cytoplasmic segment enclosed by a nuclear heterochromatin bridge or a nuclear segment enclosed by an intranuclear cleft. One type of nuclear cleft...

  17. The effect of air leakage and heat exchange on the decay of entrapped air pocket slamming oscillations

    Science.gov (United States)

    Abrahamsen, Bjørn C.; Faltinsen, Odd M.

    2011-10-01

    The phenomenon studied in this work is that of an air pocket entrapped by a free surface water wave inside a rectangular tank at a high filling level. The wave, which is a gravity wave, is caused by forced horizontal motion which is constructed in a particular way, in order to entrap an air pocket as it approaches the upper left corner of the tank. As the wave touches the roof, the air is compressed and starts to oscillate. The oscillations resemble, to some extent, the free oscillations of an underdamped mass-spring system, where the mass is related to the generalized added mass effect of the water pressure associated with the air pocket oscillations. The stiffness is due to the compressibility of the air. The reason for the damping or, more generally, the decay of the air pocket oscillations is less understood. Air leakage has been proposed as one possible reason for this decay. In this work, the role of air leakage is found not to be the reason for the decay of the air pocket oscillations, because it is not present during major parts of the impact. However, by drilling holes in the roof of the tank, the effect of leakage during the oscillations is proven to cause decay. To explain the physical source of the decay of the oscillations, damping due to heat transfer to and from the air pocket is investigated through an analytical one-dimensional steady-state model. The damping due to heat transfer is observed to play an important role. The obtained understanding of the mechanisms causing the decay of the air-pocket impact at the upper corner is believed to be relevant to other types of impacts, particularly the entrapment of air pockets on walls by breaking waves.

  18. Novel benzimidazole inhibitors bind to a unique site in the kinesin spindle protein motor domain.

    Science.gov (United States)

    Sheth, Payal R; Shipps, Gerald W; Seghezzi, Wolfgang; Smith, Catherine K; Chuang, Cheng-Chi; Sanden, David; Basso, Andrea D; Vilenchik, Lev; Gray, Kimberly; Annis, D Allen; Nickbarg, Elliott; Ma, Yao; Lahue, Brian; Herbst, Ronald; Le, Hung V

    2010-09-28

    Affinity selection-mass spectrometry (AS-MS) screening of kinesin spindle protein (KSP) followed by enzyme inhibition studies and temperature-dependent circular dichroism (TdCD) characterization was utilized to identify a series of benzimidazole compounds. This series also binds in the presence of Ispinesib, a known anticancer KSP inhibitor in phase I/II clinical trials for breast cancer. TdCD and AS-MS analyses support simultaneous binding implying existence of a novel non-Ispinesib binding pocket within KSP. Additional TdCD analyses demonstrate direct binding of these compounds to Ispinesib-resistant mutants (D130V, A133D, and A133D + D130V double mutant), further strengthening the hypothesis that the compounds bind to a distinct binding pocket. Also importantly, binding to this pocket causes uncompetitive inhibition of KSP ATPase activity. The uncompetitive inhibition with respect to ATP is also confirmed by the requirement of nucleotide for binding of the compounds. After preliminary affinity optimization, the benzimidazole series exhibited distinctive antimitotic activity as evidenced by blockade of bipolar spindle formation and appearance of monoasters. Cancer cell growth inhibition was also demonstrated either as a single agent or in combination with Ispinesib. The combination was additive as predicted by the binding studies using TdCD and AS-MS analyses. The available data support the existence of a KSP inhibitory site hitherto unknown in the literature. The data also suggest that targeting this novel site could be a productive strategy for eluding Ispinesib-resistant tumors. Finally, AS-MS and TdCD techniques are general in scope and may enable screening other targets in the presence of known drugs, clinical candidates, or tool compounds that bind to the protein of interest in an effort to identify potency-enhancing small molecules that increase efficacy and impede resistance in combination therapy. PMID:20718440

  19. Identification of a Binding Site for Unsaturated Fatty Acids in the Orphan Nuclear Receptor Nurr1.

    Science.gov (United States)

    de Vera, Ian Mitchelle S; Giri, Pankaj K; Munoz-Tello, Paola; Brust, Richard; Fuhrmann, Jakob; Matta-Camacho, Edna; Shang, Jinsai; Campbell, Sean; Wilson, Henry D; Granados, Juan; Gardner, William J; Creamer, Trevor P; Solt, Laura A; Kojetin, Douglas J

    2016-07-15

    Nurr1/NR4A2 is an orphan nuclear receptor, and currently there are no known natural ligands that bind Nurr1. A recent metabolomics study identified unsaturated fatty acids, including arachidonic acid and docosahexaenoic acid (DHA), that interact with the ligand-binding domain (LBD) of a related orphan receptor, Nur77/NR4A1. However, the binding location and whether these ligands bind other NR4A receptors were not defined. Here, we show that unsaturated fatty acids also interact with the Nurr1 LBD, and solution NMR spectroscopy reveals the binding epitope of DHA at its putative ligand-binding pocket. Biochemical assays reveal that DHA-bound Nurr1 interacts with high affinity with a peptide derived from PIASγ, a protein that interacts with Nurr1 in cellular extracts, and DHA also affects cellular Nurr1 transactivation. This work is the first structural report of a natural ligand binding to a canonical NR4A ligand-binding pocket and indicates a natural ligand can bind and affect Nurr1 function. PMID:27128111

  20. A COMPARISON OF SEMANTIC SIMILARITY MODELS IN EVALUATING CONCEPT SIMILARITY

    Directory of Open Access Journals (Sweden)

    Q. X. Xu

    2012-08-01

    Full Text Available The semantic similarities are important in concept definition, recognition, categorization, interpretation, and integration. Many semantic similarity models have been established to evaluate semantic similarities of objects or/and concepts. To find out the suitability and performance of different models in evaluating concept similarities, we make a comparison of four main types of models in this paper: the geometric model, the feature model, the network model, and the transformational model. Fundamental principles and main characteristics of these models are introduced and compared firstly. Land use and land cover concepts of NLCD92 are employed as examples in the case study. The results demonstrate that correlations between these models are very high for a possible reason that all these models are designed to simulate the similarity judgement of human mind.

  1. Comparison of Different Ranking Methods in Protein-Ligand Binding Site Prediction

    Science.gov (United States)

    Gao, Jun; Liu, Qi; Kang, Hong; Cao, Zhiwei; Zhu, Ruixin

    2012-01-01

    In recent years, although many ligand-binding site prediction methods have been developed, there has still been a great demand to improve the prediction accuracy and compare different prediction algorithms to evaluate their performances. In this work, in order to improve the performance of the protein-ligand binding site prediction method presented in our former study, a comparison of different binding site ranking lists was studied. Four kinds of properties, i.e., pocket size, distance from the protein centroid, sequence conservation and the number of hydrophobic residues, have been chosen as the corresponding ranking criterion respectively. Our studies show that the sequence conservation information helps to rank the real pockets with the most successful accuracy compared to others. At the same time, the pocket size and the distance of binding site from the protein centroid are also found to be helpful. In addition, a multi-view ranking aggregation method, which combines the information among those four properties, was further applied in our study. The results show that a better performance can be achieved by the aggregation of the complementary properties in the prediction of ligand-binding sites. PMID:22942732

  2. Learning Multi-modal Similarity

    CERN Document Server

    McFee, Brian

    2010-01-01

    In many applications involving multi-media data, the definition of similarity between items is integral to several key tasks, e.g., nearest-neighbor retrieval, classification, and recommendation. Data in such regimes typically exhibits multiple modalities, such as acoustic and visual content of video. Integrating such heterogeneous data to form a holistic similarity space is therefore a key challenge to be overcome in many real-world applications. We present a novel multiple kernel learning technique for integrating heterogeneous data into a single, unified similarity space. Our algorithm learns an optimal ensemble of kernel transfor- mations which conform to measurements of human perceptual similarity, as expressed by relative comparisons. To cope with the ubiquitous problems of subjectivity and inconsistency in multi- media similarity, we develop graph-based techniques to filter similarity measurements, resulting in a simplified and robust training procedure.

  3. Roget's Thesaurus and Semantic Similarity

    OpenAIRE

    Jarmasz, Mario; Szpakowicz, Stan

    2012-01-01

    We have implemented a system that measures semantic similarity using a computerized 1987 Roget's Thesaurus, and evaluated it by performing a few typical tests. We compare the results of these tests with those produced by WordNet-based similarity measures. One of the benchmarks is Miller and Charles' list of 30 noun pairs to which human judges had assigned similarity measures. We correlate these measures with those computed by several NLP systems. The 30 pairs can be traced back to Rubenstein ...

  4. Classification of a Haemophilus influenzae ABC transporter HI1470/71 through its cognate molybdate periplasmic binding protein, MolA

    OpenAIRE

    Tirado-Lee, Leidamarie; Lee, Allen; Rees, Douglas C.; Pinkett, Heather W.

    2011-01-01

    molA(HI1472) from H. influenzae encodes a periplasmic binding protein (PBP) that delivers substrate to the ABC transporter MolB2C2 (formerly HI1470/71). The structures of MolA with molybdate and tungstate in the binding pocket were solved to 1.6 and 1.7-Å resolution, respectively. The MolA binding protein binds molybdate and tungstate but not other oxyanions such as sulfate and phosphate, making it the first class III molybdate binding protein structurally solved. The ~100 μM binding affinity...

  5. Personalized recommendation with corrected similarity

    International Nuclear Information System (INIS)

    Personalized recommendation has attracted a surge of interdisciplinary research. Especially, similarity-based methods in applications of real recommendation systems have achieved great success. However, the computations of similarities are overestimated or underestimated, in particular because of the defective strategy of unidirectional similarity estimation. In this paper, we solve this drawback by leveraging mutual correction of forward and backward similarity estimations, and propose a new personalized recommendation index, i.e., corrected similarity based inference (CSI). Through extensive experiments on four benchmark datasets, the results show a greater improvement of CSI in comparison with these mainstream baselines. And a detailed analysis is presented to unveil and understand the origin of such difference between CSI and mainstream indices. (paper)

  6. Incidence of pocket hematoma after electrophysiological device placement:dual antiplatelet therapy versus low-molecular-weight heparin regimen

    Institute of Scientific and Technical Information of China (English)

    Yan CHEN; Xin-Cun YANG; Kang MENG; Yun-Tao LI; Ming-Dong GAO; Ze-Chun ZENG; Jin-Rong ZHANG; Hong-Liang CONG; Yin LIU; Ru ZHAO; Le-Feng WANG

    2014-01-01

    Background Given the increasing number of patients who require dual antiplatelet (DAP) therapy and electrophysiological device (EPD) placement, perioperative antiplatelet management is a current challenge. In this study, we investigated the incidence of pocket hema-toma formation after EPD placement in patients undergoing DAP therapy or an alternative low-molecular-weight heparin (LMWH) regimen. Methods This clinical observational study was performed from July 2010 to July 2012. In total, 171 patients were enrolled in the analysis after meeting the inclusion criteria. These patients were divided into two groups: 86 patients were treated with DAP therapy at the time of device implantation, and the DAP therapy was discontinued for 5 to 7 days and replaced with enoxaparin before device implantation in the other 85 patients. Adenosine phosphate (ADP)-mediated platelet aggregation and arachidonic acid-induced platelet aggregation were tested preoperatively. We compared the incidence of pocket hematoma between the two groups and the association of pocket hematoma develop-ment with ADP-mediated platelet aggregation and arachidonic acid-induced platelet aggregation.Results The incidence of pocket hema-toma in the patients who continued DAP was lower than that in the patients who replaced the dual antiplatelet regimen with LMWH (3.49%vs. 16.47%, respectively;X2 = 6.66,P < 0.01). Among the patients who continued DAP therapies, the rate of ADP-mediated platelet aggre-gation inhibition in patients with pocket hematomas was higher than that in patients without pocket hematomas. None of the patients under-going DAP or enoxaparin therapy developed pocket infection, thromboembolic events, or other serious complications. Multiple logistic re-gression analysis revealed that LMWH therapy was an independent risk factor for the development of pocket hematoma (RR = 0.054, 95%CI = 0.012-0.251). Furthermore, patients undergoing LMWH therapy were 5.1-fold more likely to develop pocket

  7. Invasion of radioactive waste burial sites by the Great Basin Pocket Mouse (Perognathus parvus)

    International Nuclear Information System (INIS)

    The invasion of burial sites by animals is a common problem documented at several nuclear facilities including Idaho National Engineering Laboratories (INEL), Savannah River, Oak Ridge, and Los Alamos. In order to establish effective deterrents for control of this problem, baseline information has been collected about specific parameters related to the potential for transport of radionuclides by animals. This study identifies parameters associated with burrowing activities of the Great Basin Pocket Mouse (Perognathus parvus) at the Hanford Site in Eastern Washington. The objectives of the study were: 1) document and compare burrow depths and soil volumes on a control site and a decommissioned radioactive waste site and 2) develop a system to estimate the depth and soil volume of burrows without requiring excavation. Animals were found to burrow deeper in the backfilled burial site (x = .77 m) than they did in the control site (x = .43 m). Burrows were probably deeper in the disturbed waste site due to limited compaction; and as a result, pocket mice have to dig deeper to maintain the integrity of the burrow system. Significant positive correlations (p<.01) were calculated from both study sites between burrow depth and soil volume and between mound diameter and soil volume. Based on these correlations, it should be possible to estimate burrow depths and soil volumes without excavation. Confidence levels and standard deviations are provided with these estimates. This method will allow estimates to be made of how much soil has been brought to the surface by pocket mice over a given period of time and may be useful in determining which waste sites could experience potential problems related to radionuclide transport. Recommendations based on these data can be used in the design of future burial facilities to prevent or mitigate the impact of encroachment by burrowing animals

  8. vi and Vim Editors Pocket Reference Support for every text editing task

    CERN Document Server

    Robbins, Arnold

    2011-01-01

    Many Unix, Linux, and Mac OS X geeks enjoy using the powerful, platform-agnostic text editors vi and Vim, but there are far too many commands for anyone to remember. Author Arnold Robbins has chosen the most valuable commands for vi, Vim, and vi's main clones-vile, elvis, and nvi-and packed them into this easy-to-browse pocket reference. You'll find commands for all kinds of editing tasks, such as programming, modifying system files, and writing and marking up articles. This second edition includes: Command-line optionsvi commands and set optionsInput mode shortcutsSubstitution and regular e

  9. Approaches for Identification of HIV-1 Entry Inhibitors Targeting gp41 Pocket

    OpenAIRE

    Debnath, Asim K.; Shibo Jiang; Xiaojie Zhu; Lanying Du; Fei Yu; Lu Lu

    2013-01-01

    The hydrophobic pocket in the HIV-1 gp41 N-terminal heptad repeat (NHR) domain plays an important role in viral fusion and entry into the host cell, and serves as an attractive target for development of HIV-1 fusion/entry inhibitors. The peptide anti-HIV drug targeting gp41 NHR, T-20 (generic name: enfuvirtide; brand name: Fuzeon), was approved by the U.S. FDA in 2003 as the first HIV fusion/entry inhibitor for treatment of HIV/AIDS patients who fail to respond to the current antiretroviral d...

  10. Landscape of protein-small ligand binding modes.

    Science.gov (United States)

    Kasahara, Kota; Kinoshita, Kengo

    2016-09-01

    Elucidating the mechanisms of specific small-molecule (ligand) recognition by proteins is a long-standing conundrum. While the structures of these molecules, proteins and ligands, have been extensively studied, protein-ligand interactions, or binding modes, have not been comprehensively analyzed. Although methods for assessing similarities of binding site structures have been extensively developed, the methods for the computational treatment of binding modes have not been well established. Here, we developed a computational method for encoding the information about binding modes as graphs, and assessing their similarities. An all-against-all comparison of 20,040 protein-ligand complexes provided the landscape of the protein-ligand binding modes and its relationships with protein- and chemical spaces. While similar proteins in the same SCOP Family tend to bind relatively similar ligands with similar binding modes, the correlation between ligand and binding similarities was not very high (R(2)  = 0.443). We found many pairs with novel relationships, in which two evolutionally distant proteins recognize dissimilar ligands by similar binding modes (757,474 pairs out of 200,790,780 pairs were categorized into this relationship, in our dataset). In addition, there were an abundance of pairs of homologous proteins binding to similar ligands with different binding modes (68,217 pairs). Our results showed that many interesting relationships between protein-ligand complexes are still hidden in the structure database, and our new method for assessing binding mode similarities is effective to find them. PMID:27327045

  11. Identification of amino acid residues in protein SRP72 required for binding to a kinked 5e motif of the human signal recognition particle RNA

    Directory of Open Access Journals (Sweden)

    Zwieb Christian

    2010-11-01

    Full Text Available Abstract Background Human cells depend critically on the signal recognition particle (SRP for the sorting and delivery of their proteins. The SRP is a ribonucleoprotein complex which binds to signal sequences of secretory polypeptides as they emerge from the ribosome. Among the six proteins of the eukaryotic SRP, the largest protein, SRP72, is essential for protein targeting and possesses a poorly characterized RNA binding domain. Results We delineated the minimal region of SRP72 capable of forming a stable complex with an SRP RNA fragment. The region encompassed residues 545 to 585 of the full-length human SRP72 and contained a lysine-rich cluster (KKKKKKKKGK at postions 552 to 561 as well as a conserved Pfam motif with the sequence PDPXRWLPXXER at positions 572 to 583. We demonstrated by site-directed mutagenesis that both regions participated in the formation of a complex with the RNA. In agreement with biochemical data and results from chymotryptic digestion experiments, molecular modeling of SRP72 implied that the invariant W577 was located inside the predicted structure of an RNA binding domain. The 11-nucleotide 5e motif contained within the SRP RNA fragment was shown by comparative electrophoresis on native polyacrylamide gels to conform to an RNA kink-turn. The model of the complex suggested that the conserved A240 of the K-turn, previously identified as being essential for the binding to SRP72, could protrude into a groove of the SRP72 RNA binding domain, similar but not identical to how other K-turn recognizing proteins interact with RNA. Conclusions The results from the presented experiments provided insights into the molecular details of a functionally important and structurally interesting RNA-protein interaction. A model for how a ligand binding pocket of SRP72 can accommodate a new RNA K-turn in the 5e region of the eukaryotic SRP RNA is proposed.

  12. Electrophoretic behavior of streptavidin complexed to a biotinylated probe : A functional screening assay for biotin-binding proteins

    OpenAIRE

    Humbert, Nicolas; Zocchi, Andrea; Ward, Thomas R.

    2006-01-01

    The biotin-binding protein streptavidin exhibits a high stability against thermal denaturation, especially when complexed to biotin. Herein we show that, in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), streptavidin is stabilized at high temperature in the presence of biotinylated fluorescent probes, such as biotin-4-fluorescein, which is incorporated within the binding pocket. In nondenaturing SDS-PAGE, streptavidin is detectable when complexed with biotin-4-fluoresce...

  13. Binding sensitivity of adefovir to the polymerase from different genotypes of HBV: molecular modeling, docking and dynamics simulation studies

    OpenAIRE

    Li, Jing; Du, Yun; Liu, Xian; Shen, Qian-cheng; Huang, Ai-Long; Zheng, Ming-Yue; Luo, Xiao-Min; Jiang, Hua-liang

    2012-01-01

    Aim: To investigate the molecular mechanisms underlying the influence of DNA polymerase from different genotypes of hepatitis B virus (HBV) on the binding affinity of adefovir (ADV). Methods: Computational approaches, including homology modeling, docking, MD simulation and MM/PBSA free energy analyses were used. Results: Sequence analyses revealed that residue 238 near the binding pocket was not only a polymorphic site but also a genotype-specific site (His238 in genotype B; Asn238 in genotyp...

  14. Self-similar aftershock rates

    CERN Document Server

    Davidsen, Jörn

    2016-01-01

    In many important systems exhibiting crackling noise --- intermittent avalanche-like relaxation response with power-law and, thus, self-similar distributed event sizes --- the "laws" for the rate of activity after large events are not consistent with the overall self-similar behavior expected on theoretical grounds. This is in particular true for the case of seismicity and a satisfying solution to this paradox has remained outstanding. Here, we propose a generalized description of the aftershock rates which is both self-similar and consistent with all other known self-similar features. Comparing our theoretical predictions with high resolution earthquake data from Southern California we find excellent agreement, providing in particular clear evidence for a unified description of aftershocks and foreshocks. This may offer an improved way of time-dependent seismic hazard assessment and earthquake forecasting.

  15. Structure of the Cyclic Nucleotide-Binding Homology Domain of the hERG Channel and Its Insight into Type 2 Long QT Syndrome.

    Science.gov (United States)

    Li, Yan; Ng, Hui Qi; Li, Qingxin; Kang, CongBao

    2016-01-01

    The human ether-à-go-go related gene (hERG) channel is crucial for the cardiac action potential by contributing to the fast delayed-rectifier potassium current. Mutations in the hERG channel result in type 2 long QT syndrome (LQT2). The hERG channel contains a cyclic nucleotide-binding homology domain (CNBHD) and this domain is required for the channel gating though molecular interactions with the eag domain. Here we present solution structure of the CNBHD of the hERG channel. The structural study reveals that the CNBHD adopts a similar fold to other KCNH channels. It is self-liganded and it contains a short β-strand that blocks the nucleotide-binding pocket in the β-roll. Folding of LQT2-related mutations in this domain was shown to be affected by point mutation. Mutations in this domain can cause protein aggregation in E. coli cells or induce conformational changes. One mutant-R752W showed obvious chemical shift perturbation compared with the wild-type, but it still binds to the eag domain. The helix region from the N-terminal cap domain of the hERG channel showed unspecific interactions with the CNBHD. PMID:27025590

  16. Learning Multi-modal Similarity

    OpenAIRE

    McFee, Brian; Lanckriet, Gert

    2010-01-01

    In many applications involving multi-media data, the definition of similarity between items is integral to several key tasks, e.g., nearest-neighbor retrieval, classification, and recommendation. Data in such regimes typically exhibits multiple modalities, such as acoustic and visual content of video. Integrating such heterogeneous data to form a holistic similarity space is therefore a key challenge to be overcome in many real-world applications. We present a novel multiple kernel learning t...

  17. Similarity measures for protein ensembles

    DEFF Research Database (Denmark)

    Lindorff-Larsen, Kresten; Ferkinghoff-Borg, Jesper

    2009-01-01

    Analyses of similarities and changes in protein conformation can provide important information regarding protein function and evolution. Many scores, including the commonly used root mean square deviation, have therefore been developed to quantify the similarities of different protein conformations...... synthetic example from molecular dynamics simulations. We then apply the algorithms to revisit the problem of ensemble averaging during structure determination of proteins, and find that an ensemble refinement method is able to recover the correct distribution of conformations better than standard single...

  18. SELF-SIMILAR TRAFFIC GENERATOR

    OpenAIRE

    Linawati Linawati; I Made Suartika

    2009-01-01

    Network traffic generator can be produced using OPNET. OPNET generates the traffic as explicit traffic or background traffic. This paper demonstrates generating traffic in OPNET 7.0 as background traffic. The traffi generator that was simulated is self-similar traffic with different Hurst parameter. The simulation results proved that OPNET with background traffic function can be as a qualified self-similar traffic generator. These results can help in investigating and analysing network perfor...

  19. Molecular similarity of MDR inhibitors

    OpenAIRE

    Simon Gibbons; Mire Zloh

    2004-01-01

    Abstract: The molecular similarity of multidrug resistance (MDR) inhibitors was evaluated using the point centred atom charge approach in an attempt to find some common features of structurally unrelated inhibitors. A series of inhibitors of bacterial MDR were studied and there is a high similarity between these in terms of their shape, presence and orientation of aromatic ring moieties. A comparison of the lipophilic properties of these molecules has also been conducted suggesting that this ...

  20. HOW DISSIMILARLY SIMILAR ARE BIOSIMILARS?

    OpenAIRE

    Ramshankar Vijayalakshmi; Kesavan Sabitha; Krishnamurthy Arvind

    2012-01-01

    Recently Biopharmaceuticals are the new chemotherapeutical agents that are called as “Biosimilars” or “follow on protein products” by the European Medicines Agency (EMA) and the American regulatory agencies (Food and Drug Administration) respectively. Biosimilars are extremely similar to the reference molecule but not identical, however close their similarities may be. A regulatory framework is therefore in place to assess the application for marketing authorisation of biosimilars. When a bi...

  1. Method of similarity for cavitation

    International Nuclear Information System (INIS)

    The knowledge of possible cavitation in subassembly nozzles of the fast reactor core implies the realization of a fluid dynamic model test. We propose a method of similarity based on the non-dimensionalization of the equation of motion for viscous capillarity fluid issued from the Cahn and Hilliard model. Taking into account the dissolved gas effect, a condition of compatibility is determined. This condition must be respected by the fluid in experiment, along with the scaling between the two similar flows. (author)

  2. Supervised Learning with Similarity Functions

    OpenAIRE

    Kar, Purushottam; Jain, Prateek

    2012-01-01

    We address the problem of general supervised learning when data can only be accessed through an (indefinite) similarity function between data points. Existing work on learning with indefinite kernels has concentrated solely on binary/multi-class classification problems. We propose a model that is generic enough to handle any supervised learning task and also subsumes the model previously proposed for classification. We give a "goodness" criterion for similarity functions w.r.t. a given superv...

  3. Using remote substituents to control solution structure and anion binding in lanthanide complexes

    DEFF Research Database (Denmark)

    Tropiano, Manuel; Blackburn, Octavia A.; Tilney, James A.;

    2013-01-01

    of the molecule, at a substantial distance from the binding pocket. Herein, we explore these remote substituent effects and explain the observed behaviour through discussion of the way in which remote substituents can influence and control the global structure of a molecule through their demands upon...... conformational space. Peripheral modifications to a binuclear lanthanide motif derived from α,α'-bis(DO3 Ayl)-m-xylene are shown to result in dramatic changes to the binding constant for isophthalate. In this system, the parent compound displays considerable conformational flexibility, yet can be assumed to bind...

  4. Representation is representation of similarities.

    Science.gov (United States)

    Edelman, S

    1998-08-01

    Advanced perceptual systems are faced with the problem of securing a principled (ideally, veridical) relationship between the world and its internal representation. I propose a unified approach to visual representation, addressing the need for superordinate and basic-level categorization and for the identification of specific instances of familiar categories. According to the proposed theory, a shape is represented internally by the responses of a small number of tuned modules, each broadly selective for some reference shape, whose similarity to the stimulus it measures. This amounts to embedding the stimulus in a low-dimensional proximal shape space spanned by the outputs of the active modules. This shape space supports representations of distal shape similarities that are veridical as Shepard's (1968) second-order isomorphisms (i.e., correspondence between distal and proximal similarities among shapes, rather than between distal shapes and their proximal representations). Representation in terms of similarities to reference shapes supports processing (e.g., discrimination) of shapes that are radically different from the reference ones, without the need for the computationally problematic decomposition into parts required by other theories. Furthermore, a general expression for similarity between two stimuli, based on comparisons to reference shapes, can be used to derive models of perceived similarity ranging from continuous, symmetric, and hierarchical ones, as in multidimensional scaling (Shepard 1980), to discrete and nonhierarchical ones, as in the general contrast models (Shepard & Arabie 1979; Tversky 1977). PMID:10097019

  5. Kinetic and structural insights into the binding of histone deacetylase 1 and 2 (HDAC1, 2) inhibitors.

    Science.gov (United States)

    Wagner, Florence F; Weïwer, Michel; Steinbacher, Stefan; Schomburg, Adrian; Reinemer, Peter; Gale, Jennifer P; Campbell, Arthur J; Fisher, Stewart L; Zhao, Wen-Ning; Reis, Surya A; Hennig, Krista M; Thomas, Méryl; Müller, Peter; Jefson, Martin R; Fass, Daniel M; Haggarty, Stephen J; Zhang, Yan-Ling; Holson, Edward B

    2016-09-15

    The structure-activity and structure-kinetic relationships of a series of novel and selective ortho-aminoanilide inhibitors of histone deacetylases (HDACs) 1 and 2 are described. Different kinetic and thermodynamic selectivity profiles were obtained by varying the moiety occupying an 11Å channel leading to the Zn(2+) catalytic pocket of HDACs 1 and 2, two paralogs with a high degree of structural similarity. The design of these novel inhibitors was informed by two ligand-bound crystal structures of truncated hHDAC2. BRD4884 and BRD7232 possess kinetic selectivity for HDAC1 versus HDAC2. We demonstrate that the binding kinetics of HDAC inhibitors can be tuned for individual isoforms in order to modulate target residence time while retaining functional activity and increased histone H4K12 and H3K9 acetylation in primary mouse neuronal cell culture assays. These chromatin modifiers, with tuned binding kinetic profiles, can be used to define the relation between target engagement requirements and the pharmacodynamic response of HDACs in different disease applications. PMID:27377864

  6. Use of sequence microdivergence in mycobacterial ortholog to analyze contributions of the water-activating loop histidine of Escherichia coli uracil-DNA glycosylase in reactant binding and catalysis

    International Nuclear Information System (INIS)

    Uracil-DNA glycosylase (Ung), a DNA repair enzyme, pioneers uracil excision repair pathway. Structural determinations and mutational analyses of the Ung class of proteins have greatly facilitated our understanding of the mechanism of uracil excision from DNA. More recently, a hybrid quantum-mechanical/molecular mechanical analysis revealed that while the histidine (H67 in EcoUng) of the GQDPYH motif (ω loop) in the active site pocket is important in positioning the reactants, it makes an unfavorable energetic contribution (penalty) in achieving the transition state intermediate. Mutational analysis of this histidine is unavailable from any of the Ung class of proteins. A complication in demonstrating negative role of a residue, especially when located within the active site pocket, is that the mutants with enhanced activity are rarely obtained. Interestingly, unlike the most Ung proteins, the H67 equivalent in the ω loop in mycobacterial Ung is represented by P67. Exploiting this natural diversity to maintain structural integrity of the active site, we transplanted an H67P mutation in EcoUng. Uracil inhibition assays and binding of a proteinaceous inhibitor, Ugi (a transition state substrate mimic), with the mutant (H67P) revealed that its active site pocket was not perturbed. The catalytic efficiency (Vmax/Km) of the mutant was similar to that of the wild type Ung. However, the mutant showed increased Km and Vmax. Together with the data from a double mutation H67P/G68T, these observations provide the first biochemical evidence for the proposed diverse roles of H67 in catalysis by Ung

  7. Double gate graphene nanoribbon field effect transistor with single halo pocket in channel region

    Science.gov (United States)

    Naderi, Ali

    2016-01-01

    A new structure for graphene nanoribbon field-effect transistors (GNRFETs) is proposed and investigated using quantum simulation with a nonequilibrium Green's function (NEGF) method. Tunneling leakage current and ambipolar conduction are known effects for MOSFET-like GNRFETs. To minimize these issues a novel structure with a simple change of the GNRFETs by using single halo pocket in the intrinsic channel region, "Single Halo GNRFET (SH-GNRFET)", is proposed. An appropriate halo pocket at source side of channel is used to modify potential distribution of the gate region and weaken band to band tunneling (BTBT). In devices with materials like Si in channel region, doping type of halo and source/drain regions are different. But, here, due to the smaller bandgap of graphene, the mentioned doping types should be the same to reduce BTBT. Simulations have shown that in comparison with conventional GNRFET (C-GNRFET), an SH-GNRFET with appropriately halo doping results in a larger ON current (Ion), smaller OFF current (Ioff), a larger ON-OFF current ratio (Ion/Ioff), superior ambipolar characteristics, a reduced power-delay product and lower delay time.

  8. Compare local pocket and global protein structure models by small structure patterns

    KAUST Repository

    Cui, Xuefeng

    2015-09-09

    Researchers proposed several criteria to assess the quality of predicted protein structures because it is one of the essential tasks in the Critical Assessment of Techniques for Protein Structure Prediction (CASP) competitions. Popular criteria include root mean squared deviation (RMSD), MaxSub score, TM-score, GDT-TS and GDT-HA scores. All these criteria require calculation of rigid transformations to superimpose the the predicted protein structure to the native protein structure. Yet, how to obtain the rigid transformations is unknown or with high time complexity, and, hence, heuristic algorithms were proposed. In this work, we carefully design various small structure patterns, including the ones specifically tuned for local pockets. Such structure patterns are biologically meaningful, and address the issue of relying on a sufficient number of backbone residue fragments for existing methods. We sample the rigid transformations from these small structure patterns; and the optimal superpositions yield by these small structures are refined and reported. As a result, among 11; 669 pairs of predicted and native local protein pocket models from the CASP10 dataset, the GDT-TS scores calculated by our method are significantly higher than those calculated by LGA. Moreover, our program is computationally much more efficient. Source codes and executables are publicly available at http://www.cbrc.kaust.edu.sa/prosta/

  9. Triple Point Collision and Origin of Unburned Gas Pockets in Irregular Detonations

    CERN Document Server

    Mahmoudi, Yasser

    2014-01-01

    The turbulent structure of an irregular detonation is studied through very high resolution numerical simulations of 600 points per half reaction length. The aim is to explore the nature of the transverse waves during the collision and reflection processes of the triple point with the channel walls. Consequently the formation and consumption mechanism of unreacted gas pockets is studied. Results show that as the triple point collides with the wall, the transverse shock interacts with the unreacted pocket. After reflection of the triple point off the wall, the transverse wave interacts with the wall. The structure found to be of a double Mach configuration and does not change before and after reflection. In the second half of the detonation cell the triple point and the transverse wave collide simultaneously with the wall. The strong transverse wave switches from a primary triple point before collision to a new one after reflection. After some time a weak triple point reflects off the wall and hence the structu...

  10. Radial-firing optical fiber tip containing conical-shaped air-pocket for biomedical applications.

    Science.gov (United States)

    Lee, Seung Ho; Ryu, Yong-Tak; Son, Dong Hoon; Jeong, Seongmook; Kim, Youngwoong; Ju, Seongmin; Kim, Bok Hyeon; Han, Won-Taek

    2015-08-10

    We report a novel radial-firing optical fiber tip containing a conical-shaped air-pocket fabricated by deforming a hollow optical fiber using electric arc-discharge process. The hollow optical fiber was fusion spliced with a conventional optical fiber, simultaneously deforming into the intagliated conical-shaped region along the longitudinal fiber-axis of the fiber due to the gradual collapse of the cavity of the hollow optical fiber. Then the distal-end of the hollow optical fiber was sealed by the additional arc-discharge in order to obstruct the inflow of an external bio-substance or liquid to the inner air surface during the surgical operations, resulting in the formation of encased air-pocket in the silica glass fiber. Due to the total internal reflection of the laser beam at the conical-shaped air surface, the laser beam (λ = 632.8 nm) was deflected to the circumferential direction up to 87 degree with respect to the fiber-axis. PMID:26367974

  11. The PocketSpacecraft.com Integrated eXploration Environment (PIXE)

    Science.gov (United States)

    Johnson, Michael

    2015-04-01

    The PocketSpacecraft.com Integrated eXploration Environment (PIXE) is an integrated generic spacecraft design, simulation, manufacturing, and operations system for the low cost mass exploration of space by amateur and professional Principle Investigators (PIs). PIs use an online tool to design Thin-Film Spacecraft/Lander/Rovers (TF-SLRs) using a library of predefined spacecraft and mission components to specify TF-SLRs in quantities ranging from one to thousands per mission, each with a typical mass <1g, surface area <1m2, and Pocket Spacecraft: Mission to the Moon' has been traditionally and crowd funded and is being prepared for flight with the goal of achieving low lunar orbit in 2016.

  12. Focused Cardiac Ultrasound Using a Pocket-Size Device in the Emergency Room

    International Nuclear Information System (INIS)

    Cardiovascular urgencies are frequent reasons for seeking medical care. Prompt and accurate medical diagnosis is critical to reduce the morbidity and mortality of these conditions. To evaluate the use of a pocket-size echocardiography in addition to clinical history and physical exam in a tertiary medical emergency care. One hundred adult patients without known cardiac or lung diseases who sought emergency care with cardiac complaints were included. Patients with ischemic changes in the electrocardiography or fever were excluded. A focused echocardiography with GE Vscan equipment was performed after the initial evaluation in the emergency room. Cardiac chambers dimensions, left and right ventricular systolic function, intracardiac flows with color, pericardium, and aorta were evaluated. The mean age was 61 ± 17 years old. The patient complaint was chest pain in 51 patients, dyspnea in 32 patients, arrhythmia to evaluate the left ventricular function in ten patients, hypotension/dizziness in five patients and edema in one patient. In 28 patients, the focused echocardiography allowed to confirm the initial diagnosis: 19 patients with heart failure, five with acute coronary syndrome, two with pulmonary embolism and two patients with cardiac tamponade. In 17 patients, the echocardiography changed the diagnosis: ten with suspicious of heart failure, two with pulmonary embolism suspicious, two with hypotension without cause, one suspicious of acute coronary syndrome, one of cardiac tamponade and one of aortic dissection. The focused echocardiography with pocket-size equipment in the emergency care may allow a prompt diagnosis and, consequently, an earlier initiation of the therapy

  13. Poverty, out-of-pocket payments and access to health care: evidence from Tajikistan.

    Science.gov (United States)

    Falkingham, Jane

    2004-01-01

    Most countries of the Former Soviet Union (FSU) have either initiated or are contemplating reform of the health sector. With negative real income growth and falling government revenues, a key concern of many governments is to secure additional finance through non-budgetary sources such as hypothecated payroll taxes, voluntary insurance, and increased private finance through patient cost-sharing. However, before such reforms can be considered, information is needed both on the current levels and distribution of household expenditures on health care, and the extent to which increased charges may affect access to health services, especially amongst the poor. This paper uses the Tajikistan Livings Standard Survey to investigate the level and distribution of out-of-pocket payments for health care in Tajikistan and to examine the extent to which such payments act as barriers to health-care access. The data show that there are significant differences in health-care utilisation rates across socio-economic groups and that these differences are related to ability to pay. Official and informal payments are acting both to deter people from seeking medical assistance and once advice has been sought, from receiving the most appropriate treatment. Despite informal exemptions, out-of-pocket payments for health care are exacting a high toll on household welfare with households being forced to sell assets or go into debt to meet the costs of care. Urgent action is needed to ensure equity in access to health care. PMID:14604611

  14. Focused Cardiac Ultrasound Using a Pocket-Size Device in the Emergency Room

    Energy Technology Data Exchange (ETDEWEB)

    Mancuso, Frederico José Neves, E-mail: frederico.mancuso@grupofleury.com.br [Disciplina de Cardiologia - Escola Paulista de Medicina - Universidade Federal de São Paulo (Unifesp), São Paulo, SP (Brazil); Disciplina de Medicina de Urgência - Escola Paulista de Medicina - Universidade Federal de São Paulo (Unifesp), São Paulo, SP (Brazil); Siqueira, Vicente Nicoliello; Moisés, Valdir Ambrósio [Disciplina de Cardiologia - Escola Paulista de Medicina - Universidade Federal de São Paulo (Unifesp), São Paulo, SP (Brazil); Gois, Aécio Flavio Teixeira [Disciplina de Medicina de Urgência - Escola Paulista de Medicina - Universidade Federal de São Paulo (Unifesp), São Paulo, SP (Brazil); Paola, Angelo Amato Vincenzo de; Carvalho, Antonio Carlos Camargo; Campos, Orlando [Disciplina de Cardiologia - Escola Paulista de Medicina - Universidade Federal de São Paulo (Unifesp), São Paulo, SP (Brazil)

    2014-12-15

    Cardiovascular urgencies are frequent reasons for seeking medical care. Prompt and accurate medical diagnosis is critical to reduce the morbidity and mortality of these conditions. To evaluate the use of a pocket-size echocardiography in addition to clinical history and physical exam in a tertiary medical emergency care. One hundred adult patients without known cardiac or lung diseases who sought emergency care with cardiac complaints were included. Patients with ischemic changes in the electrocardiography or fever were excluded. A focused echocardiography with GE Vscan equipment was performed after the initial evaluation in the emergency room. Cardiac chambers dimensions, left and right ventricular systolic function, intracardiac flows with color, pericardium, and aorta were evaluated. The mean age was 61 ± 17 years old. The patient complaint was chest pain in 51 patients, dyspnea in 32 patients, arrhythmia to evaluate the left ventricular function in ten patients, hypotension/dizziness in five patients and edema in one patient. In 28 patients, the focused echocardiography allowed to confirm the initial diagnosis: 19 patients with heart failure, five with acute coronary syndrome, two with pulmonary embolism and two patients with cardiac tamponade. In 17 patients, the echocardiography changed the diagnosis: ten with suspicious of heart failure, two with pulmonary embolism suspicious, two with hypotension without cause, one suspicious of acute coronary syndrome, one of cardiac tamponade and one of aortic dissection. The focused echocardiography with pocket-size equipment in the emergency care may allow a prompt diagnosis and, consequently, an earlier initiation of the therapy.

  15. Child Wasting in Emergency Pockets: A Meta-Analysis of Small-Scale Surveys from Ethiopia.

    Science.gov (United States)

    Altare, Chiara; Delbiso, Tefera Darge; Guha-Sapir, Debarati

    2016-02-01

    Child undernutrition is a major public health concern in Ethiopia (stunting national prevalence: 44%; wasting: 10%), despite the overall improvement in child health status during the last decade. Hundreds of small-scale surveys are conducted in Ethiopia's emergency pockets under ENCU's supervision. We reviewed the evidence from small-scale surveys conducted between 2008 and 2013 with two objectives: to provide a summary estimate of wasting prevalence from emergency pockets and to examine reasons for variation in prevalence estimates. We created a dataset by combining data from the Complex Emergency Database, the Famine Early Warning System Network and the Armed Conflict Location Event Data. We conducted a meta-analysis of small-scale surveys using a random effects model with known within-study heterogeneity. The influence of survey covariates on estimated prevalence was investigated with meta-regression techniques. We included 158 surveys in the analysis. A high degree of heterogeneity among surveys was observed. The overall estimate of wasting prevalence was 10.6% (95% CI 9.8-11.4), with differences among regions and between residents and refugees. Meta-regression results showed that vaccination coverage, child mortality, diarrhea prevalence and food insecurity are significantly associated with wasting prevalence. Child care and displacement status were not. Aggregated analysis of small-scale surveys provides insights into the prevalence of wasting and factors explaining its variation. It can also guide survey planning towards areas with limited data availability. PMID:26828512

  16. Social Values as Arguments: Similar is Convincing

    Directory of Open Access Journals (Sweden)

    Gregory R Maio

    2014-08-01

    Full Text Available Politicians, philosophers, and rhetors engage in co-value argumentation: appealing to one value in order to support another value (e.g., equality leads to freedom. Across four experiments in the United Kingdom and India, we found that the psychological relatedness of values affects the persuasiveness of the arguments that bind them. Experiment 1 found that participants were more persuaded by arguments citing values that fulfilled similar motives than by arguments citing opposing values. Experiments 2 and 3 replicated this result using a wider variety of values, while finding that the effect is stronger among people higher in need for cognition and that the effect is mediated by the greater plausibility of co-value arguments that link motivationally compatible values. Experiment 4 extended the effect to real-world arguments taken from political propaganda and replicated the mediating effect of argument plausibility. The findings highlight the importance of value relatedness in argument persuasiveness.

  17. Thermodynamic evaluation and modeling of proton and water exchange associated with benzamidine and berenil binding to ß-trypsin

    Directory of Open Access Journals (Sweden)

    M.T. Pereira

    2005-11-01

    Full Text Available Serine-proteases are involved in vital processes in virtually all species. They are important targets for researchers studying the relationships between protein structure and activity, for the rational design of new pharmaceuticals. Trypsin was used as a model to assess a possible differential contribution of hydration water to the binding of two synthetic inhibitors. Thermodynamic parameters for the association of bovine ß-trypsin (homogeneous material, observed 23,294.4 ± 0.2 Da, theoretical 23,292.5 Da with the inhibitors benzamidine and berenil at pH 8.0, 25ºC and with 25 mM CaCl2, were determined using isothermal titration calorimetry and the osmotic stress method. The association constant for berenil was about 12 times higher compared to the one for benzamidine (binding constants are K = 596,599 ± 25,057 and 49,513 ± 2,732 M-1, respectively; the number of binding sites is the same for both ligands, N = 0.99 ± 0.05. Apparently the driving force responsible for this large difference of affinity is not due to hydrophobic interactions because the variation in heat capacity (DCp, a characteristic signature of these interactions, was similar in both systems tested (-464.7 ± 23.9 and -477.1 ± 86.8 J K-1 mol-1 for berenil and benzamidine, respectively. The results also indicated that the enzyme has a net gain of about 21 water molecules regardless of the inhibitor tested. It was shown that the difference in affinity could be due to a larger number of interactions between berenil and the enzyme based on computational modeling. The data support the view that pharmaceuticals derived from benzamidine that enable hydrogen bond formation outside the catalytic binding pocket of ß-trypsin may result in more effective inhibitors.

  18. Similarity measures for face recognition

    CERN Document Server

    Vezzetti, Enrico

    2015-01-01

    Face recognition has several applications, including security, such as (authentication and identification of device users and criminal suspects), and in medicine (corrective surgery and diagnosis). Facial recognition programs rely on algorithms that can compare and compute the similarity between two sets of images. This eBook explains some of the similarity measures used in facial recognition systems in a single volume. Readers will learn about various measures including Minkowski distances, Mahalanobis distances, Hansdorff distances, cosine-based distances, among other methods. The book also summarizes errors that may occur in face recognition methods. Computer scientists "facing face" and looking to select and test different methods of computing similarities will benefit from this book. The book is also useful tool for students undertaking computer vision courses.

  19. Similarity Measures for Comparing Biclusterings.

    Science.gov (United States)

    Horta, Danilo; Campello, Ricardo J G B

    2014-01-01

    The comparison of ordinary partitions of a set of objects is well established in the clustering literature, which comprehends several studies on the analysis of the properties of similarity measures for comparing partitions. However, similarity measures for clusterings are not readily applicable to biclusterings, since each bicluster is a tuple of two sets (of rows and columns), whereas a cluster is only a single set (of rows). Some biclustering similarity measures have been defined as minor contributions in papers which primarily report on proposals and evaluation of biclustering algorithms or comparative analyses of biclustering algorithms. The consequence is that some desirable properties of such measures have been overlooked in the literature. We review 14 biclustering similarity measures. We define eight desirable properties of a biclustering measure, discuss their importance, and prove which properties each of the reviewed measures has. We show examples drawn and inspired from important studies in which several biclustering measures convey misleading evaluations due to the absence of one or more of the discussed properties. We also advocate the use of a more general comparison approach that is based on the idea of transforming the original problem of comparing biclusterings into an equivalent problem of comparing clustering partitions with overlapping clusters. PMID:26356865

  20. Approaches to Sequence Similarity Representation

    OpenAIRE

    Sokolov, Artem; Rachkovskij, Dmitri

    2006-01-01

    We discuss several approaches to similarity preserving coding of symbol sequences and possible connections of their distributed versions to metric embeddings. Interpreting sequence representation methods with embeddings can help develop an approach to their analysis and may lead to discovering useful properties.

  1. A square from similar rectangles

    OpenAIRE

    Dorichenko, Sergey; Skopenkov, Mikhail

    2013-01-01

    In the present popular science paper we determine when a square can be dissected into rectangles similar to a given rectangle. The approach to the question is based on a physical interpretation using electrical networks. Only secondary school background is assumed in the paper.

  2. HOW DISSIMILARLY SIMILAR ARE BIOSIMILARS?

    Directory of Open Access Journals (Sweden)

    Ramshankar Vijayalakshmi

    2012-05-01

    Full Text Available Recently Biopharmaceuticals are the new chemotherapeutical agents that are called as “Biosimilars” or “follow on protein products” by the European Medicines Agency (EMA and the American regulatory agencies (Food and Drug Administration respectively. Biosimilars are extremely similar to the reference molecule but not identical, however close their similarities may be. A regulatory framework is therefore in place to assess the application for marketing authorisation of biosimilars. When a biosimilar is similar to the reference biopharmaceutical in terms of safety, quality, and efficacy, it can be registered. It is important to document data from clinical trials with a view of similar safety and efficacy. If the development time for a generic medicine is around 3 years, a biosimilar takes about 6-9 years. Generic medicines need to demonstrate bioequivalence only unlike biosimilars that need to conduct phase I and Phase III clinical trials. In this review, different biosimilars that are already being used successfully in the field on Oncology is discussed. Their similarity, differences and guidelines to be followed before a clinically informed decision to be taken, is discussed. More importantly the regulatory guidelines that are operational in India with a work flow of making a biosimilar with relevant dos and dont’s are discussed. For a large populous country like India, where with improved treatments in all sectors including oncology, our ageing population is increasing. For the health care of this sector, we need more newer, cheaper and effective biosimilars in the market. It becomes therefore important to understand the regulatory guidelines and steps to come up with more biosimilars for the existing population and also more information is mandatory for the practicing clinicians to translate these effectively into clinical practice.

  3. Improved cardiovascular diagnostic accuracy by pocket size imaging device in non-cardiologic outpatients: the NaUSiCa (Naples Ultrasound Stethoscope in Cardiology study

    Directory of Open Access Journals (Sweden)

    Schiattarella Pier

    2010-11-01

    Full Text Available Abstract Miniaturization has evolved in the creation of a pocket-size imaging device which can be utilized as an ultrasound stethoscope. This study assessed the additional diagnostic power of pocket size device by both experts operators and trainees in comparison with physical examination and its appropriateness of use in comparison with standard echo machine in a non-cardiologic population. Three hundred four consecutive non cardiologic outpatients underwent a sequential assessment including physical examination, pocket size imaging device and standard Doppler-echo exam. Pocket size device was used by both expert operators and trainees (who received specific training before the beginning of the study. All the operators were requested to give only visual, qualitative insights on specific issues. All standard Doppler-echo exams were performed by expert operators. One hundred two pocket size device exams were performed by experts and two hundred two by trainees. The time duration of the pocket size device exam was 304 ± 117 sec. Diagnosis of cardiac abnormalities was made in 38.2% of cases by physical examination and in 69.7% of cases by physical examination + pocket size device (additional diagnostic power = 31.5%, p In conclusion, pocket size device showed a relevant additional diagnostic value in comparison with physical examination. Sensitivity and specificity were good in experts and suboptimal in trainees. Specificity was particularly influenced by the level of experience. Training programs are needed for pocket size device users.

  4. Design of a Novel Low Cost Point of Care Tampon (POCkeT Colposcope for Use in Resource Limited Settings.

    Directory of Open Access Journals (Sweden)

    Christopher T Lam

    Full Text Available Current guidelines by WHO for cervical cancer screening in low- and middle-income countries involves visual inspection with acetic acid (VIA of the cervix, followed by treatment during the same visit or a subsequent visit with cryotherapy if a suspicious lesion is found. Implementation of these guidelines is hampered by a lack of: trained health workers, reliable technology, and access to screening facilities. A low cost ultra-portable Point of Care Tampon based digital colposcope (POCkeT Colposcope for use at the community level setting, which has the unique form factor of a tampon, can be inserted into the vagina to capture images of the cervix, which are on par with that of a state of the art colposcope, at a fraction of the cost. A repository of images to be compiled that can be used to empower front line workers to become more effective through virtual dynamic training. By task shifting to the community setting, this technology could potentially provide significantly greater cervical screening access to where the most vulnerable women live. The POCkeT Colposcope's concentric LED ring provides comparable white and green field illumination at a fraction of the electrical power required in commercial colposcopes. Evaluation with standard optical imaging targets to assess the POCkeT Colposcope against the state of the art digital colposcope and other VIAM technologies.Our POCkeT Colposcope has comparable resolving power, color reproduction accuracy, minimal lens distortion, and illumination when compared to commercially available colposcopes. In vitro and pilot in vivo imaging results are promising with our POCkeT Colposcope capturing comparable quality images to commercial systems.The POCkeT Colposcope is capable of capturing images suitable for cervical lesion analysis. Our portable low cost system could potentially increase access to cervical cancer screening in limited resource settings through task shifting to community health workers.

  5. BINDING ISOTHERMS SURFACTANT-PROTEINS

    OpenAIRE

    Elena Irina Moater; Cristiana Radulescu; Ionica Ionita

    2011-01-01

    The interactions between surfactants and proteins shows some similarities with interactions between surfactants and polymers, but the hydrophobic amphoteric nature of proteins and their secondary and tertiary structure components make them different from conventional polymer systems. Many studies from the past about surfactant - proteins bonding used the dialysis techniques. Other techniques used to determine the binding isotherm, included ultrafiltration, ultracentrifugation, potentiometry, ...

  6. Influence of a mutation in the ATP-binding region of Ca2+/calmodulin-dependent protein kinase II on its interaction with peptide substrates.

    Science.gov (United States)

    Praseeda, Mullasseril; Pradeep, Kurup K; Krupa, Ananth; Krishna, S Sri; Leena, Suseela; Kumar, R Rajeev; Cheriyan, John; Mayadevi, Madhavan; Srinivasan, Narayanaswamy; Omkumar, Ramakrishnapillai V

    2004-03-01

    CaMKII (Ca2+/calmodulin-dependent protein kinase II) is expressed in high concentrations in the brain and is found enriched in the postsynaptic densities. The enzyme is activated by the binding of calmodulin to the autoregulatory domain in the presence of high levels of intracellular Ca2+, which causes removal of auto-inhibition from the N-terminal catalytic domain. Knowledge of the 3D (three-dimensional) structure of this enzyme at atomic resolution is restricted to the association domain, a region at the extreme C-terminus. The catalytic domain of CaMKII shares high sequence similarity with CaMKI. The 3D structure of the catalytic core of CaMKI comprises ATP- and substrate-binding regions in a cleft between two distinct lobes, similar to the structures of all protein kinases solved to date. Mutation of Glu-60, a residue in the ATP-binding region of CaMKII, to glycine exerts different effects on phosphorylation of two peptide substrates, syntide and NR2B ( N -methyl-D-aspartate receptor subunit 2B) 17-mer. Although the mutation caused increases in the Km values for phosphorylation for both the peptide substrates, the effect on the kcat values for each was different. The kcat value decreased in the case of syntide, whereas it increased in the case of the NR2B peptide as a result of the mutation. This resulted in a significant decrease in the apparent kcat/Km value for syntide, but the change was minimal for the NR2B peptide. These results indicate that different catalytic mechanisms are employed by the kinase for the two peptides. Molecular modelling suggests structural changes are likely to occur at the peptide-binding pocket in the active state of the enzyme as a consequence of the Glu-60-->Gly mutation. PMID:14558884

  7. Measurements of cosmic radiation doses in civil aircraft by pocket dosimeter (II). Results for international air lines

    International Nuclear Information System (INIS)

    Next to previous results for domestic airlines, the present ones concerned international lines. The measurement was done in about 70 international flights from December 1992-September 2000, using Aloka PDM-101 semiconductor electronic pocket dosimeter worn at the breast position. In some cases, dose rate was also measured by intermittent reading. The integrating dose was found to increase with the time of flight and dose rate change reflected the pattern of flight. Data are preliminary but it was thought that the pocket dosimeter can provide the whole dose and dose rate which are the sum of ionizing and neutron components. (K.H.)

  8. Retrieval of similar chess positions

    OpenAIRE

    Ganguly, Debasis; LEVELING, JOHANNES; Jones, Gareth J.F.

    2014-01-01

    We address the problem of retrieving chess game positions similar to a given query position from a collection of archived chess games. We investigate this problem from an information retrieval (IR) perspective. The advantage of our proposed IR-based approach is that it allows using the standard inverted organization of stored chess positions, leading to an ecient retrieval. Moreover, in contrast to retrieving exactly identical board positions, the IR-based approach is able to provide approxim...

  9. Scaling Group Testing Similarity Search

    OpenAIRE

    Iscen, Ahmet; Amsaleg, Laurent; Furon, Teddy

    2016-01-01

    The large dimensionality of modern image feature vectors, up to thousands of dimensions, is challenging the high dimensional indexing techniques. Traditional approaches fail at returning good quality results within a response time that is usable in practice. However, similarity search techniques inspired by the group testing framework have recently been proposed in an attempt to specifically defeat the curse of dimensionality. Yet, group testing does not scale and fails at indexing very large...

  10. Study of PIN diode based pocket dosimeter for gamma and beta radiation

    International Nuclear Information System (INIS)

    A pocket dosimeter, based on PN junction Si Semiconductor detector earlier was developed for the measurement of dose equivalent in the field of gamma and beta radiation. This dosemeter was insensitive to beta radiation which is primary requirement as a legal personal dosemeter from IEE standards. This dosemeter works on a high power 3V Li battery along with a micro power DC-DC converter to get 3.3V needed to power the circuit. It has a 6 digit LCD digital display along with battery low indication. It measures the dose range of 1- 99999 μSv. The photon energy dependence of the dosimeter from 60 keV to 1.2 MeV is ± 30% for gamma radiation and ± 40% for beta. Further work is in progress to bring beta response within acceptable limit and to display beta and gamma response separately as Hp (0.07) and Hp (10). (author)

  11. Low-Level Laser Therapy (LLLT) for periodontal pockets: a review

    Science.gov (United States)

    Pribac, Valentin; Todea, Carmen; Duma, Virgil-Florin

    2016-03-01

    The applications of lasers in medicine, both in the field of diagnosis and treatment are gaining momentum. In dentistry in particular, numerous types of lasers with a wide range of characteristics are being utilized in all fields. In consequence, a lot of experience and knowledge has been gained in the last two decades in this domain; this resulted in the development of novel technologies and devices. A brief overview is made in the first part of this article on these topics. The treatment of periodontal disease with laser therapy is pointed out, as well as the photodynamic therapy which is using LLLT for the activation of the sensitizing gel that is introduced in the periodontal pockets. This paper reviews also the application of photodynamic therapy in clinical trials which have different results; a standardization of the protocol utilized for this procedure is concluded to be necessary.

  12. Approaching an organic semimetal: Electron pockets at the Fermi level for a p-benzoquinonemonoimine zwitterion

    Energy Technology Data Exchange (ETDEWEB)

    Rosa, Luis G.; Velev, Julian [Department of Physics and Electronics, University of Puerto Rico, Humacao (United States); Institute for Functional Nanomaterials, University of Puerto Rico, San Juan (United States); Department of Physics and Astronomy, Nebraska Center for Materials and Nanoscience, University of Nebraska-Lincoln, NE (United States); Zhang, Zhengzheng [Department of Physics, University of Puerto Rico, Rio Piedras, San Juan (United States); Alvira, Jose; Vega, Omar; Diaz, Gerson [Department of Physics and Electronics, University of Puerto Rico, Humacao (United States); Routaboul, Lucie; Braunstein, Pierre [Laboratoire de Chimie de Coordination, Institut de Chimie (UMR 7177 CNRS), Universite de Strasbourg (France); Doudin, Bernard [Institut de Physique, Applique de Physique et Chimie des Materiaux de Strasbourg, Universite Louis Pasteur Strasbourg (France); Losovyj, Yaroslav B. [Institute for Functional Nanomaterials, University of Puerto Rico, San Juan (United States); J. Bennett Johnston Sr. Center for Advanced Microstructures and Devices, Louisiana State Univ., Baton Rouge, LA (United States); Dowben, Peter A. [Institute for Functional Nanomaterials, University of Puerto Rico, San Juan (United States)

    2012-08-15

    There is compelling evidence of electron pockets, at the Fermi level, in the band structure for an organic zwitterion molecule of the p-benzoquinonemonoimine type. The electronic structure of the zwitterion molecular film has a definite, although small, density of states evident at the Fermi level as well as a nonzero inner potential and thus is very different from a true insulator. In spite of a small Brillouin zone, significant band width is observed in the intermolecular band dispersion. The results demonstrate that Bloch's theorem applies to the wave vector dependence of the electronic band structure formed from the molecular orbitals of adjacent molecules in a molecular thin film of a p-benzoquinonemonoimine type zwitterion. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  13. Changing the acceptor identity of a transfer RNA by altering nucleotides in a "variable pocket".

    Science.gov (United States)

    McClain, W H; Foss, K

    1988-09-30

    The specificity of tRNA(Arg) (arginine transfer RNA) for aminoacylation (its acceptor identity) were first identified by computer analysis and then examined with amber suppressor tRNAs in Escherichia coli. On replacing two nucleotides in tRNA(Phe) (phenylalanine transfer RNA) with the corresponding nucleotides from tRNA(Arg), the acceptor identity of the resulting tRNA was changed to that of tRNA(Arg). The nucleotides used in the identity transformation occupy a "variable pocket" structure on the surface of the tRNA molecule where two single-stranded loop segments interact. The middle nucleotide in the anticodon also probably contributes to the interaction, since an amber suppressor of tRNA(Arg) had an acceptor identity for lysine as well as arginine. PMID:2459773

  14. Out of pocket payments and social health insurance for private hospital care: Evidence from Greece.

    Science.gov (United States)

    Grigorakis, Nikolaos; Floros, Christos; Tsangari, Haritini; Tsoukatos, Evangelos

    2016-08-01

    The Greek state has reduced their funding on health as part of broader efforts to limit the large fiscal deficits and rising debt ratios to GDP. Benefits cuts and limitations of Social Health Insurance (SHI) reimbursements result in substantial Out of Pocket (OOP) payments in the Greek population. In this paper, we examine social health insurance's risk pooling mechanisms and the catastrophic impact that OOP payments may have on insured's income and well-being. Using data collected from a cross sectional survey in Greece, we find that the OOP payments for inpatient care in private hospitals have a positive relationship with SHI funding. Moreover, we show that the SHI funding is inadequate to total inpatient financing. We argue that the Greek health policy makers have to give serious consideration to the perspective of a SHI system which should be supplemented by the Private Health Insurance (PHI) sector. PMID:27421172

  15. Postoperative blunt trauma to 7.5 mm scleral pocket wounds.

    Science.gov (United States)

    Stevens, J D; Claoué, C M; Steele, A D

    1994-05-01

    Two patients received blunt trauma to the operated eye after phacoemulsification cataract surgery. Both patients had a three-step 7.5 mm chord width, 3.0 mm long, curving incision, extending from sclera into clear cornea. One patient had rupture of the scleral tunnel and horizontal suture 20 days after surgery. The intraocular lens was dislocated into and along the scleral tunnel. The second patient had direct trauma four days after surgery, resulting in cheese-wiring of the horizontal nylon 10-0 suture and wound leakage but no other sequelae. Blunt trauma after scleral pocket phacoemulsification cataract surgery may result in clinical wound dehiscence if sufficient force is sustained. PMID:8064613

  16. SPATIO-TEXTUAL SIMILARITY JOIN

    Directory of Open Access Journals (Sweden)

    Ch Shylaja and Supreethi K.P

    2015-07-01

    Full Text Available Data mining is the process of discovering interesting patterns and knowledge from large amounts of data. Spatial databases store large space related data, such as maps, preprocessed remote sensing or medical imaging data. Modern mobile phones and mobile devices are equipped with GPS devices; this is the reason for the Location based services to gain significant attention. These Location based services generate large amounts of spatio- textual data which contain both spatial location and textual description. The spatiotextual objects have different representations because of deviations in GPS or due to different user descriptions. This calls for the need of efficient methods to integrate spatio-textual data. Spatio-textual similarity join meets this need. Spatio-textual similarity join: Given two sets of spatio-textual data, it finds all the similar pairs. Filter and refine framework will be developed to device the algorithms. The prefix filter technique will be extended to generate spatial and textual signatures and inverted indexes will be built on top of these signatures. Candidate pairs will be found using these indexes. Finally the candidate pairs will be refined to get the result. MBR-prefix based signature will be used to prune dissimilar objects. Hybrid signature will be used to support spatial and textual pruning simultaneously.

  17. Roget's Thesaurus and Semantic Similarity

    CERN Document Server

    Jarmasz, Mario

    2012-01-01

    We have implemented a system that measures semantic similarity using a computerized 1987 Roget's Thesaurus, and evaluated it by performing a few typical tests. We compare the results of these tests with those produced by WordNet-based similarity measures. One of the benchmarks is Miller and Charles' list of 30 noun pairs to which human judges had assigned similarity measures. We correlate these measures with those computed by several NLP systems. The 30 pairs can be traced back to Rubenstein and Goodenough's 65 pairs, which we have also studied. Our Roget's-based system gets correlations of .878 for the smaller and .818 for the larger list of noun pairs; this is quite close to the .885 that Resnik obtained when he employed humans to replicate the Miller and Charles experiment. We further evaluate our measure by using Roget's and WordNet to answer 80 TOEFL, 50 ESL and 300 Reader's Digest questions: the correct synonym must be selected amongst a group of four words. Our system gets 78.75%, 82.00% and 74.33% of ...

  18. Focused Cardiac Ultrasound Using a Pocket-Size Device in the Emergency Room

    Directory of Open Access Journals (Sweden)

    Frederico José Neves Mancuso

    2014-12-01

    Full Text Available Background: Cardiovascular urgencies are frequent reasons for seeking medical care. Prompt and accurate medical diagnosis is critical to reduce the morbidity and mortality of these conditions. Objective: To evaluate the use of a pocket-size echocardiography in addition to clinical history and physical exam in a tertiary medical emergency care. Methods: One hundred adult patients without known cardiac or lung diseases who sought emergency care with cardiac complaints were included. Patients with ischemic changes in the electrocardiography or fever were excluded. A focused echocardiography with GE Vscan equipment was performed after the initial evaluation in the emergency room. Cardiac chambers dimensions, left and right ventricular systolic function, intracardiac flows with color, pericardium, and aorta were evaluated. Results: The mean age was 61 ± 17 years old. The patient complaint was chest pain in 51 patients, dyspnea in 32 patients, arrhythmia to evaluate the left ventricular function in ten patients, hypotension/dizziness in five patients and edema in one patient. In 28 patients, the focused echocardiography allowed to confirm the initial diagnosis: 19 patients with heart failure, five with acute coronary syndrome, two with pulmonary embolism and two patients with cardiac tamponade. In 17 patients, the echocardiography changed the diagnosis: ten with suspicious of heart failure, two with pulmonary embolism suspicious, two with hypotension without cause, one suspicious of acute coronary syndrome, one of cardiac tamponade and one of aortic dissection. Conclusion: The focused echocardiography with pocket-size equipment in the emergency care may allow a prompt diagnosis and, consequently, an earlier initiation of the therapy.

  19. Development of Pocket Vision Screener and its effectiveness at screening visual acuity deficits

    Directory of Open Access Journals (Sweden)

    Monica Raja

    2014-01-01

    Full Text Available Aim: The aim was to construct a visual acuity chart and find its effectiveness at screening visual acuity deficits. Materials and Methods: Two phases were involved in this study.Construction of the screener: Ten Sloan letters (C, D, H, K, N, O, R, S, V, and Z were selected and the letters were constructed and reduced to 0.2 logMAR acuity size (6.92 mm for viewing at 3 m. The screener contains three lines with seven letters in each. Few combinations of the seven letter sequences were chosen based on the row legibility scores. Three seven letter combinations close to the median of all combinations were selected, such that maximum difficulty score difference between the lines are <1%. Finding the effectiveness of the screener: 100 literate subjects with unaided visual acuity better than or equal to 6/60 were recruited for the study. Unaided visual acuity was tested using both the newly constructed Pocket Vision Screener and a logMAR visual acuity chart and the time taken to measure the visual acuity using both the charts was noted. Results: The mean age of the subjects was 43 ± 17 years. Subjects were classified as normal or deficient based on the logMAR visual acuity measurement. The screener was found to have 81% sensitivity, 94% specificity. The positive and negative predictive values were found to be 91% and 87%, respectively. A significant difference (P < 0.001 was found in the time taken to record visual acuity using both the charts. Conclusion: The Pocket Vision Screener can be used as a quick and accurate tool to screen subjects for visual acuity deficits, being highly sensitive, specific, and cost-effective.

  20. Solute-vacancy binding in aluminum

    International Nuclear Information System (INIS)

    Previous efforts to understand solute-vacancy binding in aluminum alloys have been hampered by a scarcity of reliable, quantitative experimental measurements. Here, we report a large database of solute-vacancy binding energies determined from first-principles density functional calculations. The calculated binding energies agree well with accurate measurements where available, and provide an accurate predictor of solute-vacancy binding in other systems. We find: (i) some common solutes in commercial Al alloys (e.g., Cu and Mg) possess either very weak (Cu), or even repulsive (Mg), binding energies. Hence, we assert that some previously reported large binding energies for these solutes are erroneous. (ii) Large binding energies are found for Sn, Cd and In, confirming the proposed mechanism for the reduced natural aging in Al-Cu alloys containing microalloying additions of these solutes. (iii) In addition, we predict that similar reduction in natural aging should occur with additions of Si, Ge and Au. (iv) Even larger binding energies are found for other solutes (e.g., Pb, Bi, Sr, Ba), but these solutes possess essentially no solubility in Al. (v) We have explored the physical effects controlling solute-vacancy binding in Al. We find that there is a strong correlation between binding energy and solute size, with larger solute atoms possessing a stronger binding with vacancies. (vi) Most transition-metal 3d solutes do not bind strongly with vacancies, and some are even energetically strongly repelled from vacancies, particularly for the early 3d solutes, Ti and V

  1. Drug binding properties of neonatal albumin

    DEFF Research Database (Denmark)

    Brodersen, R; Honoré, B

    1989-01-01

    Neonatal and adult albumin was isolated by gel chromatography on Sephacryl S-300, from adult and umbilical cord serum, respectively. Binding of monoacetyl-diamino-diphenyl sulfone, warfarin, sulfamethizole, and diazepam was studied by means of equilibrium dialysis and the binding data were analyzed...... by the method of several acceptable fitted curves. It was found that the binding affinity to neonatal albumin is less than to adult albumin for monoacetyl-diamino-diphenyl sulfone and warfarin. Sulfamethizole binding to the neonatal protein is similarly reduced when more than one molecule of the drug...... is bound per albumin molecule, and binding of the first sulfamethizole molecule is possibly reduced as well. Diazepam binds with equal affinity to the fetal and adult proteins. Among the two main albumin drug-binding functions, for warfarin and diazepam, the former is thus compromised in the newborn...

  2. Evolved streptavidin mutants reveal key role of loop residue in high-affinity binding

    OpenAIRE

    Magalhães, Maria L. B.; Czekster, Clarissa Melo; Guan, Rong; Malashkevich, Vladimir N.; Almo, Steven C.; Levy, Matthew

    2011-01-01

    We have performed a detailed analysis of streptavidin variants with altered specificity towards desthiobiotin. In addition to changes in key residues which widen the ligand binding pocket and accommodate the more structurally flexible desthiobiotin, the data revealed the role of a key, non-active site mutation at the base of the flexible loop (S52G) which slows dissociation of this ligand by approximately sevenfold. Our data suggest that this mutation results in the loss of a stabilizing cont...

  3. Evaluating the binding efficiency of pheromone binding protein with its natural ligand using molecular docking and fluorescence analysis

    Science.gov (United States)

    Ilayaraja, Renganathan; Rajkumar, Ramalingam; Rajesh, Durairaj; Muralidharan, Arumugam Ramachandran; Padmanabhan, Parasuraman; Archunan, Govindaraju

    2014-06-01

    Chemosignals play a crucial role in social and sexual communication among inter- and intra-species. Chemical cues are bound with protein that is present in the pheromones irrespective of sex are commonly called as pheromone binding protein (PBP). In rats, the pheromone compounds are bound with low molecular lipocalin protein α2u-globulin (α2u). We reported farnesol is a natural endogenous ligand (compound) present in rat preputial gland as a bound volatile compound. In the present study, an attempt has been made through computational method to evaluating the binding efficiency of α2u with the natural ligand (farnesol) and standard fluorescent molecule (2-naphthol). The docking analysis revealed that the binding energy of farnesol and 2-naphthol was almost equal and likely to share some binding pocket of protein. Further, to extrapolate the results generated through computational approach, the α2u protein was purified and subjected to fluorescence titration and binding assay. The results showed that the farnesol is replaced by 2-naphthol with high hydrophobicity of TYR120 in binding sites of α2u providing an acceptable dissociation constant indicating the binding efficiency of α2u. The obtained results are in corroboration with the data made through computational approach.

  4. Pheromone binding proteins of Epiphyas postvittana (Lepidoptera: Tortricidae) are encoded at a single locus.

    Science.gov (United States)

    Newcomb, R D; Sirey, T M; Rassam, M; Greenwood, D R

    2002-11-01

    The light brown apple moth, Epiphyas postvittana (Tortricidae: Lepidoptera) uses a blend of (E)-11-tetradecenyl acetate and (E,E)-9,11-tetradecadienyl acetate as its sex pheromone. Odorant binding proteins, abundant in the antennae of male and female E. postvittana, were separated by native PAGE to reveal four major proteins with distinct mobilities. Microsequencing of their N-terminal residues showed that two were general odorant binding proteins (GOBPs) while two were pheromone binding proteins (PBPs). Full length cDNAs encoding these proteins were amplified using a combination of PCR and RACE-PCR. Sequence of the GOBPs revealed two genes (EposGOBP1, EposGOBP2), similar to orthologues in other species of Lepidoptera. Eleven cDNAs of the PBP gene were amplified, cloned and sequenced revealing two major phylogenetic clusters of PBP sequences differing by six amino acid substitutions. The position of the six amino acid differences on the protein was predicted by mapping onto the three-dimensional structure of PBP of Bombyx mori. All six substitutions were predicted to fall on the outside of the protein away from the inner pheromone binding pocket. One substitution does fall close to the putative dimerisation region of the protein (Ser63Thr). Expression of three of the cDNAs in a baculovirus expression system revealed that one class encodes an electrophoretically slow form (EposPBP1-12) while the other encodes a fast form (EposPBP1-2, EposPBP1-3). A native Western of these expressed proteins compared with antennal protein extracts demonstrated that PBP is also expressed in female antennae and that PBP may be present as a dimer as well as a monomer in E. postvittana. The fast and slow forms of EposPBP1 are allelic. Westerns on single antennal pair protein extracts and allele-specific PCR from genomic DNA both show a segregating pattern of inheritance in laboratory and wild populations. Radio labelled (E)-11-tetradecenyl acetate binds to both fast and slow PBP forms in

  5. Insulin binding to individual rat skeletal muscles

    International Nuclear Information System (INIS)

    Studies of insulin binding to skeletal muscle, performed using sarcolemmal membrane preparations or whole muscle incubations of mixed muscle or typical red (soleus, psoas) or white [extensor digitorum longus (EDL), gastrocnemius] muscle, have suggested that red muscle binds more insulin than white muscle. We have evaluated this hypothesis using cryostat sections of unfixed tissue to measure insulin binding in a broad range of skeletal muscles; many were of similar fiber-type profiles. Insulin binding per square millimeter of skeletal muscle slice was measured by autoradiography and computer-assisted densitometry. We found a 4.5-fold range in specific insulin tracer binding, with heart and predominantly slow-twitch oxidative muscles (SO) at the high end and the predominantly fast-twitch glycolytic (FG) muscles at the low end of the range. This pattern reflects insulin sensitivity. Evaluation of displacement curves for insulin binding yielded linear Scatchard plots. The dissociation constants varied over a ninefold range (0.26-2.06 nM). Binding capacity varied from 12.2 to 82.7 fmol/mm2. Neither binding parameter was correlated with fiber type or insulin sensitivity; e.g., among three muscles of similar fiber-type profile, the EDL had high numbers of low-affinity binding sites, whereas the quadriceps had low numbers of high-affinity sites. In summary, considerable heterogeneity in insulin binding was found among hindlimb muscles of the rat, which can be attributed to heterogeneity in binding affinities and the numbers of binding sites. It can be concluded that a given fiber type is not uniquely associated with a set of insulin binding parameters that result in high or low binding

  6. Yeast TATA-binding protein TFIID binds to TATA elements with both consensus and nonconsensus DNA sequences.

    OpenAIRE

    S. Hahn; Buratowski, S.; Sharp, P A; Guarente, L

    1989-01-01

    The DNA binding properties of the yeast TATA element-binding protein TFIID were investigated. The affinity (apparent equilibrium dissociation constant) of TFIID for the adenovirus major late promoter consensus TATA element is 2 x 10(-9) M, a value similar to the affinity of gene-specific regulatory proteins for their binding sites. TFIID binding is highly specific and recognizes nonspecific sites with approximately 10(5)-fold lower affinity. Despite this specificity, TFIID also binds with hig...

  7. In silico docking of forchlorfenuron (FCF to septins suggests that FCF interferes with GTP binding.

    Directory of Open Access Journals (Sweden)

    Dimitrios Angelis

    Full Text Available Septins are GTP-binding proteins that form cytoskeleton-like filaments, which are essential for many functions in eukaryotic organisms. Small molecule compounds that disrupt septin filament assembly are valuable tools for dissecting septin functions with high temporal control. To date, forchlorfenuron (FCF is the only compound known to affect septin assembly and functions. FCF dampens the dynamics of septin assembly inducing the formation of enlarged stable polymers, but the underlying mechanism of action is unknown. To investigate how FCF binds and affects septins, we performed in silico simulations of FCF docking to all available crystal structures of septins. Docking of FCF with SEPT2 and SEPT3 indicated that FCF interacts preferentially with the nucleotide-binding pockets of septins. Strikingly, FCF is predicted to form hydrogen bonds with residues involved in GDP-binding, mimicking nucleotide binding. FCF docking with the structure of SEPT2-GppNHp, a nonhydrolyzable GTP analog, and SEPT7 showed that FCF may assume two alternative non-overlapping conformations deeply into and on the outer side of the nucleotide-binding pocket. Surprisingly, FCF was predicted to interact with the P-loop Walker A motif GxxxxGKS/T, which binds the phosphates of GTP, and the GTP specificity motif AKAD, which interacts with the guanine base of GTP, and highly conserved amino acids including a threonine, which is critical for GTP hydrolysis. Thus, in silico FCF exhibits a conserved mechanism of binding, interacting with septin signature motifs and residues involved in GTP binding and hydrolysis. Taken together, our results suggest that FCF stabilizes septins by locking them into a conformation that mimics a nucleotide-bound state, preventing further GTP binding and hydrolysis. Overall, this study provides the first insight into how FCF may bind and stabilize septins, and offers a blueprint for the rational design of FCF derivatives that could target septins with

  8. Mechanisms for similarity based cooperation

    Science.gov (United States)

    Traulsen, A.

    2008-06-01

    Cooperation based on similarity has been discussed since Richard Dawkins introduced the term “green beard” effect. In these models, individuals cooperate based on an aribtrary signal (or tag) such as the famous green beard. Here, two different models for such tag based cooperation are analysed. As neutral drift is important in both models, a finite population framework is applied. The first model, which we term “cooperative tags” considers a situation in which groups of cooperators are formed by some joint signal. Defectors adopting the signal and exploiting the group can lead to a breakdown of cooperation. In this case, conditions are derived under which the average abundance of the more cooperative strategy exceeds 50%. The second model considers a situation in which individuals start defecting towards others that are not similar to them. This situation is termed “defective tags”. It is shown that in this case, individuals using tags to cooperate exclusively with their own kind dominate over unconditional cooperators.

  9. Characterization of a gene family encoding SEA (sea-urchin sperm protein, enterokinase and agrin-domain proteins with lectin-like and heme-binding properties from Schistosoma japonicum.

    Directory of Open Access Journals (Sweden)

    Evaristus Chibunna Mbanefo

    Full Text Available BACKGROUND: We previously identified a novel gene family dispersed in the genome of Schistosoma japonicum by retrotransposon-mediated gene duplication mechanism. Although many transcripts were identified, no homolog was readily identifiable from sequence information. METHODOLOGY/PRINCIPAL FINDINGS: Here, we utilized structural homology modeling and biochemical methods to identify remote homologs, and characterized the gene products as SEA (sea-urchin sperm protein, enterokinase and agrin-domain containing proteins. A common extracellular domain in this family was structurally similar to SEA-domain. SEA-domain is primarily a structural domain, known to assist or regulate binding to glycans. Recombinant proteins from three members of this gene family specifically interacted with glycosaminoglycans with high affinity, with potential implication in ligand acquisition and immune evasion. Similar approach was used to identify a heme-binding site on the SEA-domain. The heme-binding mode showed heme molecule inserted into a hydrophobic pocket, with heme iron putatively coordinated to two histidine axial ligands. Heme-binding properties were confirmed using biochemical assays and UV-visible absorption spectroscopy, which showed high affinity heme-binding (K D = 1.605×10(-6 M and cognate spectroscopic attributes of hexa-coordinated heme iron. The native proteins were oligomers, antigenic, and are localized on adult worm teguments and gastrodermis; major host-parasite interfaces and site for heme detoxification and acquisition. CONCLUSIONS: The results suggest potential role, at least in the nucleation step of heme crystallization (hemozoin formation, and as receptors for heme uptake. Survival strategies exploited by parasites, including heme homeostasis mechanism in hemoparasites, are paramount for successful parasitism. Thus, assessing prospects for application in disease intervention is warranted.

  10. Co-current air-water flow in downward sloping pipes: Transport of capacity reducing gas pockets in wastewater mains

    NARCIS (Netherlands)

    Pothof, I.W.M.

    2011-01-01

    Air-water flow is an undesired condition in many systems for the transportation of water or wastewater. Air in storm water tunnels may get trapped and negatively affect the system. Air pockets in hydropower tunnels or sewers may cause blow-back events and inadmissible pressure spikes. Water pipes an

  11. Effects of high-frequency electromagnetic fields emitted from card readers of access control systems on electronic pocket dosimeters

    Energy Technology Data Exchange (ETDEWEB)

    Deji, Shizuhiko [Graduate School of Environmental Studies, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8602 (Japan); Nishizawa, Kunihide [Radioisotope Research Center, Nagoya University, Furo-cho, Chlkusa-ku, Nagoya 464-8602 (Japan)]. E-mail: j45616a@nucc.cc.nagoya-u.ac.jp

    2005-06-01

    High-frequency electromagnetic fields in the 120 kHz band emitted from card readers for access control systems caused abnormally high doses on electronic pocket dosimeters (EPDs). All EPDs recovered their normal performance by resetting after the exposure ceased. The electric and magnetic immunity levels of the EPDs were estimated by using the distances needed to prevent electromagnetic interference.

  12. Out-of-pocket payments and community-wide health outcomes: an examination of influenza vaccination subsidies in Japan.

    Science.gov (United States)

    Ibuka, Yoko; Bessho, Shun-Ichiro

    2016-07-01

    While studies have shown that reductions in out-of-pocket payments for vaccination generally encourages vaccination uptake, research on the impact on health outcomes has rarely been examined. Thus, the present study, using municipal-level survey data on a subsidy programme for influenza vaccination in Japan that covers the entire country, examines how reductions in out-of-pocket payments for vaccination among non-elderly individuals through a subsidy programme affected regional-level influenza activity. We find that payment reductions are negatively correlated with the number of weeks with a high influenza alert in that region, although the correlation varied across years. At the same time, we find no significant correlation between payment reductions and the total duration of influenza outbreaks (i.e. periods with a moderate or high alert). Given that a greater number of weeks with a high alert indicates a severer epidemic, our findings suggest that reductions in out-of-pocket payments for influenza vaccination among the non-elderly had a positive impact on community-wide health outcomes, indicating that reduced out-of-pocket payments contributes to the effective control of severe influenza epidemics. This suggests that payment reductions could benefit not only individuals by providing them with better access to preventive care, as has been shown previously, but also communities as a whole by shortening the duration of epidemics. PMID:26894514

  13. Performance Indexes: Similarities and Differences

    Directory of Open Access Journals (Sweden)

    André Machado Caldeira

    2013-06-01

    Full Text Available The investor of today is more rigorous on monitoring a financial assets portfolio. He no longer thinks only in terms of the expected return (one dimension, but in terms of risk-return (two dimensions. Thus new perception is more complex, since the risk measurement can vary according to anyone’s perception; some use the standard deviation for that, others disagree with this measure by proposing others. In addition to this difficulty, there is the problem of how to consider these two dimensions. The objective of this essay is to study the main performance indexes through an empirical study in order to verify the differences and similarities for some of the selected assets. One performance index proposed in Caldeira (2005 shall be included in this analysis.

  14. Features Based Text Similarity Detection

    CERN Document Server

    Kent, Chow Kok

    2010-01-01

    As the Internet help us cross cultural border by providing different information, plagiarism issue is bound to arise. As a result, plagiarism detection becomes more demanding in overcoming this issue. Different plagiarism detection tools have been developed based on various detection techniques. Nowadays, fingerprint matching technique plays an important role in those detection tools. However, in handling some large content articles, there are some weaknesses in fingerprint matching technique especially in space and time consumption issue. In this paper, we propose a new approach to detect plagiarism which integrates the use of fingerprint matching technique with four key features to assist in the detection process. These proposed features are capable to choose the main point or key sentence in the articles to be compared. Those selected sentence will be undergo the fingerprint matching process in order to detect the similarity between the sentences. Hence, time and space usage for the comparison process is r...

  15. Semantically enabled image similarity search

    Science.gov (United States)

    Casterline, May V.; Emerick, Timothy; Sadeghi, Kolia; Gosse, C. A.; Bartlett, Brent; Casey, Jason

    2015-05-01

    Georeferenced data of various modalities are increasingly available for intelligence and commercial use, however effectively exploiting these sources demands a unified data space capable of capturing the unique contribution of each input. This work presents a suite of software tools for representing geospatial vector data and overhead imagery in a shared high-dimension vector or embedding" space that supports fused learning and similarity search across dissimilar modalities. While the approach is suitable for fusing arbitrary input types, including free text, the present work exploits the obvious but computationally difficult relationship between GIS and overhead imagery. GIS is comprised of temporally-smoothed but information-limited content of a GIS, while overhead imagery provides an information-rich but temporally-limited perspective. This processing framework includes some important extensions of concepts in literature but, more critically, presents a means to accomplish them as a unified framework at scale on commodity cloud architectures.

  16. Validity of a Smartphone-Based Fall Detection Application on Different Phones Worn on a Belt or in a Trouser Pocket.

    Science.gov (United States)

    Vermeulen, Joan; Willard, Sarah; Aguiar, Bruno; De Witte, Luc P

    2015-01-01

    The objective of this study was to evaluate the sensitivity and specificity of a smartphone-based fall detection application when different smartphone models are worn on a belt or in a trouser pocket. Eight healthy adults aged between 18 and 24 years old simulated 10 different types of true falls, 5 different types of falls with recovery, and 11 daily activities, five consecutive times. Participants wore one smartphone in a pocket that was attached to their belt and another one in their trouser pocket. All smartphones were equipped with a built-in accelerometer and the fall detection application. Four participants tested the application on a Samsung S3 and four tested the application on a Samsung S3 mini. Sensitivity scores were .75 (Samsung S3 belt), .88 (Samsung S3 mini trouser pocket), and .90 (Samsung S3 mini belt/Samsung S3 trouser pocket). Specificity scores were .87 (Samsung S3 trouser pocket), .91 (Samsung S3 mini trouser pocket), .97 (Samsung S3 belt), and .99 (Samsung S3 mini belt). These results suggest that an application on a smartphone can generate valid fall alarms when worn on a belt or in a trouser pocket. However, sensitivity should be improved before implementation of the application in practice. PMID:26132221

  17. The binding sites for cocaine and dopamine in the dopamine transporter overlap

    DEFF Research Database (Denmark)

    Beuming, Thijs; Kniazeff, Julie; Bergmann, Marianne L; Shi, Lei; Gracia, Luis; Raniszewska, Klaudia; Newman, Amy Hauck; Javitch, Jonathan A; Weinstein, Harel; Gether, Ulrik; Løland, Claus Juul

    2008-01-01

    Cocaine is a widely abused substance with psychostimulant effects that are attributed to inhibition of the dopamine transporter (DAT). We present molecular models for DAT binding of cocaine and cocaine analogs constructed from the high-resolution structure of the bacterial transporter homolog Leu......T. Our models suggest that the binding site for cocaine and cocaine analogs is deeply buried between transmembrane segments 1, 3, 6 and 8, and overlaps with the binding sites for the substrates dopamine and amphetamine, as well as for benztropine-like DAT inhibitors. We validated our models by detailed...... mutagenesis and by trapping the radiolabeled cocaine analog [3H]CFT in the transporter, either by cross-linking engineered cysteines or with an engineered Zn2+-binding site that was situated extracellularly to the predicted common binding pocket. Our data demonstrate the molecular basis for the competitive...

  18. Out-of-pocket cost of managing sick newborns in Enugu, southeast Nigeria

    Directory of Open Access Journals (Sweden)

    Ekwochi U

    2014-01-01

    Full Text Available Uchenna Ekwochi,1 D Chidiebere Osuorah,3 Ikenna K Ndu,1 Osita U Ezenwosu,2 Ogechukwu F Amadi,1 Ikenna C Nwokoye,1 O Israel Odetunde2 1Department of Pediatrics, Enugu State University Teaching Hospital, Parklane, Nigeria; 2Department of Pediatrics, University of Nigeria Teaching Hospital, Enugu, Nigeria; 3Child Survival Unit, Medical Research Council (UK, The Gambia unit, Fajara, The Gambia Background: Neonatal illnesses usually require long hospital stays and specialized care and/or facilities, which usually results in huge medical bills. With more than 70% of people in Nigeria living on less than US$2 per day, these bills are not affordable to many families' livelihoods. Aim: This study aims to determine the average cost of managing neonatal illnesses in Enugu in southeast Nigeria and the proportion of family income spent on these illnesses. It further seeks to ascertain the cost of various components in the management of neonatal diseases. Methods: This is a longitudinal and descriptive study involving 106 newborns admitted to the sick baby unit of the Enugu State University Teaching Hospital and the out-of-pocket medical expenditure in the management of their illnesses. Results: A hundred and six newborns participated in the study. All (100% medical bills were out-of-pocket payments, and 103 (97.2% of these were catastrophic health expenditure (more than 10% of total family monthly income. The average duration of hospital stay and cost of managing a neonatal illness was 12.86±8.81 days and ₦36,382±19,389.72 (US$223±119, respectively. This expenditure amounted to 157%, 71%, and 25% of total monthly family income for the low, middle, and upper socioeconomic class families, respectively, with a mean percentage of 85%. Families with a total monthly income of less than ₦10,000 (US$61, ₦10,000–49,999 (US$61–306, and ₦50,000–100,000 (US$306–612 and more than ₦100,000 (US$612 on average spent 683%, 108%, 54%, and 20% of their

  19. The comparison of minocycline oral-rinse and gel on pocket depth

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    Eka Fitria Augustina

    2010-03-01

    Full Text Available Background: Infection disease is still considered as a prominent disease in many developing countries, like Indonesia. The most oral infection disease is periodontitis. Despite scaling and root planning as the main therapy, minocycline as adjunct therapy has already been used for periodontitis. There are a lot of media used, such as oral rinse and gel. Many researches even have also shown that the use of minocycline as adjunct therapy can decrease inflammation in periodontitis. Like tetracycline, minocycline as an anti inflammatory and anticollagenase is also considered to be very effective for the treatment of periodontitis. Media of minocycline that are available are gel, fiber, and oral rinse, as the newest one. Purpose: The purpose of this research is to examine the comparison of 0.2% oral rinse minocycline and 2% minocycline gel to reduce the pocket depth. Method: The samples were divided into two groups, the first group using oral rinse and the second one using gel after scaling. Result: There was no statistically significant difference between the group with minocycline gel and oral rinse. Conclusion: The application of 2% minocycline gel or 0.2% minocycline mouth wash after scaling and root planning has the same effect in reducing pocket depth.Latar belakang: Penyakit infeksi masih merupakan kasus yang menonjol di banyak negara berkembang, seperti Indonesia. Infeksi rongga mulut yang banyak terjadi adalah periodontitis. Selain terapi utama yaitu skeling dan root planning, menggunakan minosiklin sebagai terapi tambahan telah banyak digunakan, seperti obat kumur dan gel. Banyak penelitian menunjukkan bahwa penggunaan minosiklin sebagai terapi tambahan dapat menurunkan keradangan pada pasien periodontitis. Seperti tetrasiklin, minosiklin sebagai anti keradangan dan anti kolagenase, sangat efektif sebagai perawatan periodontitis. Media minosiklin yang banyak digunakan di antaranya yaitu gel, fiber, dan obat kumur yang terbaru. Tujuan: Tujuan

  20. X-ray Crystal Structure of the Novel Enhanced-Affinity Glucocorticoid Agonist Fluticasone Furoate in the Glucocorticoid Receptor−Ligand Binding Domain

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    Biggadike, Keith; Bledsoe, Randy K.; Hassell, Anne M.; Kirk, Barrie E.; McLay, Iain M.; Shewchuk, Lisa M.; Stewart, Eugene L. (GSKNC); (GSK)

    2008-07-08

    An X-ray crystal structure is reported for the novel enhanced-affinity glucocorticoid agonist fluticasone furoate (FF) in the ligand binding domain of the glucocorticoid receptor. Comparison of this structure with those of dexamethasone and fluticasone propionate shows the 17{alpha} furoate ester to occupy more fully the lipophilic 17{alpha} pocket on the receptor, which may account for the enhanced glucocorticoid receptor binding of FF.