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Sample records for au-rich signature motif

  1. Motif signatures of transcribed enhancers

    KAUST Repository

    Kleftogiannis, Dimitrios

    2017-09-14

    In mammalian cells, transcribed enhancers (TrEn) play important roles in the initiation of gene expression and maintenance of gene expression levels in spatiotemporal manner. One of the most challenging questions in biology today is how the genomic characteristics of enhancers relate to enhancer activities. This is particularly critical, as several recent studies have linked enhancer sequence motifs to specific functional roles. To date, only a limited number of enhancer sequence characteristics have been investigated, leaving space for exploring the enhancers genomic code in a more systematic way. To address this problem, we developed a novel computational method, TELS, aimed at identifying predictive cell type/tissue specific motif signatures. We used TELS to compile a comprehensive catalog of motif signatures for all known TrEn identified by the FANTOM5 consortium across 112 human primary cells and tissues. Our results confirm that distinct cell type/tissue specific motif signatures characterize TrEn. These signatures allow discriminating successfully a) TrEn from random controls, proxy of non-enhancer activity, and b) cell type/tissue specific TrEn from enhancers expressed and transcribed in different cell types/tissues. TELS codes and datasets are publicly available at http://www.cbrc.kaust.edu.sa/TELS.

  2. Spectroscopic Signatures and Structural Motifs of Dopamine: a Computational Study

    Science.gov (United States)

    Srivastava, Santosh Kumar; Singh, Vipin Bahadur

    2016-06-01

    Dopamine (DA) is an essential neurotransmitter in the central nervous system and it plays integral role in numerous brain functions including behaviour, cognition, emotion, working memory and associated learning. In the present work the conformational landscapes of neutral and protonated dopamine have been investigated in the gas phase and in aqueous solution by MP2 and DFT (M06-2X, ωB97X-D, B3LYP and B3LYP-D3) methods. Twenty lowest energy structures of neutral DA were subjected to geometry optimization and the gauche conformer, GIa, was found to be the lowest gas phase structure at the each level of theory in agreement with the experimental rotational spectroscopy. All folded gauche conformers (GI) where lone electron pair of the NH2 group is directed towards the π system of the aromatic ring ( 'non up' ) are found more stable in the gas phase. While in aqueous solution, all those gauche conformers (GII) where lone electron pair of the NH2 group is directed opposite from the π system of the aromatic ring ('up' structures) are stabilized significantly.Nine lowest energy structures, protonated at the amino group, are optimized at the same MP2/aug-cc-pVDZ level of theory. In the most stable gauche structures, g-1 and g+1, mainly electrostatic cation - π interaction is further stabilized by significant dispersion forces as predicted by the substantial differences between the DFT and dispersion corrected DFT-D3 calculations. In aqueous environment the intra-molecular cation- π distance in g-1 and g+1 isomers, slightly increases compared to the gas phase and the magnitude of the cation- π interaction is reduced relative to the gas phase, because solvation of the cation decreases its interaction energy with the π face of aromatic system. The IR intensity of the bound N-H+ stretching mode provides characteristic 'IR spectroscopic signatures' which can reflect the strength of cation- π interaction energy. The CC2 lowest lying S1 ( 1ππ* ) excited state of neutral

  3. Structural relationships in the lysozyme superfamily: significant evidence for glycoside hydrolase signature motifs.

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    Alexandre Wohlkönig

    Full Text Available BACKGROUND: Chitin is a polysaccharide that forms the hard, outer shell of arthropods and the cell walls of fungi and some algae. Peptidoglycan is a polymer of sugars and amino acids constituting the cell walls of most bacteria. Enzymes that are able to hydrolyze these cell membrane polymers generally play important roles for protecting plants and animals against infection with insects and pathogens. A particular group of such glycoside hydrolase enzymes share some common features in their three-dimensional structure and in their molecular mechanism, forming the lysozyme superfamily. RESULTS: Besides having a similar fold, all known catalytic domains of glycoside hydrolase proteins of lysozyme superfamily (families and subfamilies GH19, GH22, GH23, GH24 and GH46 share in common two structural elements: the central helix of the all-α domain, which invariably contains the catalytic glutamate residue acting as general-acid catalyst, and a β-hairpin pointed towards the substrate binding cleft. The invariant β-hairpin structure is interestingly found to display the highest amino acid conservation in aligned sequences of a given family, thereby allowing to define signature motifs for each GH family. Most of such signature motifs are found to have promising performances for searching sequence databases. Our structural analysis further indicates that the GH motifs participate in enzymatic catalysis essentially by containing the catalytic water positioning residue of inverting mechanism. CONCLUSIONS: The seven families and subfamilies of the lysozyme superfamily all have in common a β-hairpin structure which displays a family-specific sequence motif. These GH β-hairpin motifs contain potentially important residues for the catalytic activity, thereby suggesting the participation of the GH motif to catalysis and also revealing a common catalytic scheme utilized by enzymes of the lysozyme superfamily.

  4. Using sequence signatures and kink-turn motifs in knowledge-based statistical potentials for RNA structure prediction.

    Science.gov (United States)

    Bayrak, Cigdem Sevim; Kim, Namhee; Schlick, Tamar

    2017-05-19

    Kink turns are widely occurring motifs in RNA, located in internal loops and associated with many biological functions including translation, regulation and splicing. The associated sequence pattern, a 3-nt bulge and G-A, A-G base-pairs, generates an angle of ∼50° along the helical axis due to A-minor interactions. The conserved sequence and distinct secondary structures of kink-turns (k-turn) suggest computational folding rules to predict k-turn-like topologies from sequence. Here, we annotate observed k-turn motifs within a non-redundant RNA dataset based on sequence signatures and geometrical features, analyze bending and torsion angles, and determine distinct knowledge-based potentials with and without k-turn motifs. We apply these scoring potentials to our RAGTOP (RNA-As-Graph-Topologies) graph sampling protocol to construct and sample coarse-grained graph representations of RNAs from a given secondary structure. We present graph-sampling results for 35 RNAs, including 12 k-turn and 23 non k-turn internal loops, and compare the results to solved structures and to RAGTOP results without special k-turn potentials. Significant improvements are observed with the updated scoring potentials compared to the k-turn-free potentials. Because k-turns represent a classic example of sequence/structure motif, our study suggests that other such motifs with sequence signatures and unique geometrical features can similarly be utilized for RNA structure prediction and design. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  5. A PEF/Y substrate recognition and signature motif plays a critical role in DAPK-related kinase activity.

    Science.gov (United States)

    Temmerman, Koen; de Diego, Iñaki; Pogenberg, Vivian; Simon, Bertrand; Jonko, Weronika; Li, Xun; Wilmanns, Matthias

    2014-02-20

    Knowledge about protein kinase substrate preferences is biased toward residues immediately adjacent to the site of phosphorylation. By a combined structural, biochemical, and cellular approach, we have discovered an unexpected substrate recognition element with the consensus sequence PEF/Y in the tumor suppressor death-associated protein kinase 1. This motif can be effectively blocked by a specific pseudosubstrate-type interaction with an autoregulatory domain of this kinase. In this arrangement, the central PEF/Y glutamate interacts with a conserved arginine distant to the phosphorylation site in sequence and structure. We also demonstrate that the element is crucial for kinase activity regulation and substrate recognition. The PEF/Y motif distinguishes close death-associated protein kinase relatives from canonical calcium/calmodulin-dependent protein kinases. Insight into this signature and mode of action offers new opportunities to identify specific small molecule inhibitors in PEF/Y-containing protein kinases. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Requirement for asparagine in the aquaporin NPA sequence signature motifs for cation exclusion

    DEFF Research Database (Denmark)

    Wree, Dorothea; Wu, Binghua; Zeuthen, Thomas

    2011-01-01

    Two highly conserved NPA motifs are a hallmark of the aquaporin (AQP) family. The NPA triplets form N-terminal helix capping structures with the Asn side chains located in the centre of the water or solute-conducting channel, and are considered to play an important role in AQP selectivity. Although...... electrophysiology, we found that an analogous mammalian AQP1 N76S mutant excluded protons and potassium ions, but leaked sodium ions, providing an argument for the overwhelming prevalence of Asn over other amino acids. We conclude that, at the first position in the NPA motifs, only Asn provides efficient helix cap...

  7. Identification of E-cadherin signature motifs functioning as cleavage sites for Helicobacter pylori HtrA

    Science.gov (United States)

    Schmidt, Thomas P.; Perna, Anna M.; Fugmann, Tim; Böhm, Manja; Jan Hiss; Haller, Sarah; Götz, Camilla; Tegtmeyer, Nicole; Hoy, Benjamin; Rau, Tilman T.; Neri, Dario; Backert, Steffen; Schneider, Gisbert; Wessler, Silja

    2016-03-01

    The cell adhesion protein and tumour suppressor E-cadherin exhibits important functions in the prevention of gastric cancer. As a class-I carcinogen, Helicobacter pylori (H. pylori) has developed a unique strategy to interfere with E-cadherin functions. In previous studies, we have demonstrated that H. pylori secretes the protease high temperature requirement A (HtrA) which cleaves off the E-cadherin ectodomain (NTF) on epithelial cells. This opens cell-to-cell junctions, allowing bacterial transmigration across the polarised epithelium. Here, we investigated the molecular mechanism of the HtrA-E-cadherin interaction and identified E-cadherin cleavage sites for HtrA. Mass-spectrometry-based proteomics and Edman degradation revealed three signature motifs containing the [VITA]-[VITA]-x-x-D-[DN] sequence pattern, which were preferentially cleaved by HtrA. Based on these sites, we developed a substrate-derived peptide inhibitor that selectively bound and inhibited HtrA, thereby blocking transmigration of H. pylori. The discovery of HtrA-targeted signature sites might further explain why we detected a stable 90 kDa NTF fragment during H. pylori infection, but also additional E-cadherin fragments ranging from 105 kDa to 48 kDa in in vitro cleavage experiments. In conclusion, HtrA targets E-cadherin signature sites that are accessible in in vitro reactions, but might be partially masked on epithelial cells through functional homophilic E-cadherin interactions.

  8. ISFOLD: structure prediction of base pairs in non-helical RNA motifs from isostericity signatures in their sequence alignments.

    Science.gov (United States)

    Mokdad, Ali; Frankel, Alan D

    2008-04-01

    The existence and identity of non-Watson-Crick base pairs (bps) within RNA bulges, internal loops, and hairpin loops cannot reliably be predicted by existing algorithms. We have developed the Isfold (Isosteric Folding) program as a tool to examine patterns of nucleotide substitutions from sequence alignments or mutation experiments and identify plausible bp interactions. We infer these interactions based on the observation that each non-Watson-Crick bp has a signature pattern of isosteric substitutions where mutations can be made that preserve the 3D structure. Isfold produces a dynamic representation of predicted bps within defined motifs in order of their probabilities. The software was developed under Windows XP, and is capable of running on PC and MAC with Matlab 7.1 (SP3) or higher. A PC stand-alone version that does not require Matlab also is available. This software and a user manual are freely available at www.ucsf.edu/frankel/isfold.

  9. Comparative analyses of the thermodynamic RNA binding signatures of different types of RNA recognition motifs.

    Science.gov (United States)

    Samatanga, Brighton; Cléry, Antoine; Barraud, Pierre; Allain, Frédéric H-T; Jelesarov, Ilian

    2017-06-02

    RNA recognition motifs (RRMs) are structurally versatile domains important in regulation of alternative splicing. Structural mechanisms of sequence-specific recognition of single-stranded RNAs (ssRNAs) by RRMs are well understood. The thermodynamic strategies are however unclear. Therefore, we utilized microcalorimetry and semi-empirical analyses to comparatively analyze the cognate ssRNA binding thermodynamics of four different RRM domains, each with a different RNA binding mode. The different binding modes are: canonical binding to the β-sheet surface; canonical binding with involvement of N- and C-termini; binding to conserved loops; and binding to an α-helix. Our results identify enthalpy as the sole and general force driving association at physiological temperatures. Also, networks of weak interactions are a general feature regulating stability of the different RRM-ssRNA complexes. In agreement, non-polyelectrolyte effects contributed between ∼75 and 90% of the overall free energy of binding in the considered complexes. The various RNA binding modes also displayed enormous heat capacity differences, that upon dissection revealed large differential changes in hydration, conformations and dynamics upon binding RNA. Altogether, different modes employed by RRMs to bind cognate ssRNAs utilize various thermodynamics strategies during the association process. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  10. Signature Motifs Identify an Acinetobacter Cif Virulence Factor with Epoxide Hydrolase Activity*

    Science.gov (United States)

    Bahl, Christopher D.; Hvorecny, Kelli L.; Bridges, Andrew A.; Ballok, Alicia E.; Bomberger, Jennifer M.; Cady, Kyle C.; O'Toole, George A.; Madden, Dean R.

    2014-01-01

    Endocytic recycling of the cystic fibrosis transmembrane conductance regulator (CFTR) is blocked by the CFTR inhibitory factor (Cif). Originally discovered in Pseudomonas aeruginosa, Cif is a secreted epoxide hydrolase that is transcriptionally regulated by CifR, an epoxide-sensitive repressor. In this report, we investigate a homologous protein found in strains of the emerging nosocomial pathogens Acinetobacter nosocomialis and Acinetobacter baumannii (“aCif”). Like Cif, aCif is an epoxide hydrolase that carries an N-terminal secretion signal and can be purified from culture supernatants. When applied directly to polarized airway epithelial cells, mature aCif triggers a reduction in CFTR abundance at the apical membrane. Biochemical and crystallographic studies reveal a dimeric assembly with a stereochemically conserved active site, confirming our motif-based identification of candidate Cif-like pathogenic EH sequences. Furthermore, cif expression is transcriptionally repressed by a CifR homolog (“aCifR”) and is induced in the presence of epoxides. Overall, this Acinetobacter protein recapitulates the essential attributes of the Pseudomonas Cif system and thus may facilitate airway colonization in nosocomial lung infections. PMID:24474692

  11. Signature motifs identify an Acinetobacter Cif virulence factor with epoxide hydrolase activity.

    Science.gov (United States)

    Bahl, Christopher D; Hvorecny, Kelli L; Bridges, Andrew A; Ballok, Alicia E; Bomberger, Jennifer M; Cady, Kyle C; O'Toole, George A; Madden, Dean R

    2014-03-14

    Endocytic recycling of the cystic fibrosis transmembrane conductance regulator (CFTR) is blocked by the CFTR inhibitory factor (Cif). Originally discovered in Pseudomonas aeruginosa, Cif is a secreted epoxide hydrolase that is transcriptionally regulated by CifR, an epoxide-sensitive repressor. In this report, we investigate a homologous protein found in strains of the emerging nosocomial pathogens Acinetobacter nosocomialis and Acinetobacter baumannii ("aCif"). Like Cif, aCif is an epoxide hydrolase that carries an N-terminal secretion signal and can be purified from culture supernatants. When applied directly to polarized airway epithelial cells, mature aCif triggers a reduction in CFTR abundance at the apical membrane. Biochemical and crystallographic studies reveal a dimeric assembly with a stereochemically conserved active site, confirming our motif-based identification of candidate Cif-like pathogenic EH sequences. Furthermore, cif expression is transcriptionally repressed by a CifR homolog ("aCifR") and is induced in the presence of epoxides. Overall, this Acinetobacter protein recapitulates the essential attributes of the Pseudomonas Cif system and thus may facilitate airway colonization in nosocomial lung infections.

  12. Acinetobacter Insertion Sequence ISAba11 Belongs to a Novel Family That Encodes Transposases with a Signature HHEK Motif

    Science.gov (United States)

    Rieck, Barbara; Tourigny, David S.; Crosatti, Marialuisa; Schmid, Ralf; Kochar, Mandira; Harrison, Ewan M.; Ou, Hong-Yu; Turton, Jane F.

    2012-01-01

    Experimental and in silico PCR analysis targeting ISAba11 and TnAbaR islands in 196 epidemiologically unrelated Acinetobacter strains representative of ≥19 species were performed. The first two Acinetobacter baumannii ISAba11 elements identified had been found to map to the same site on TnAbaR transposons. However, no further evidence of physical linkage between the two elements was demonstrated. Indeed, examination of 25 definite or putative insertion sites suggested limited sequence specificity. Importantly, an aacC1-tagged version of ISAba11 was shown to actively transpose in A. baumannii. Similarity searches identified nine iso-ISAba11 elements in Acinetobacter and one in Enhydrobacter and single representatives of four distant homologs in bacteria belonging to the phyla “Cyanobacteria” and Proteobacteria. Phylogenetic, sequence, and structural analyses of ISAba11 and/or its associated transposase (TnpISAba11) suggested that these elements be assigned to a new family. All five homologs encode transposases with a shared extended signature comprising 16 invariant residues within the N2, N3, and C1 regions, four of which constituted the cardinal ISAba11 family HHEK motif that is substituted for the YREK DNA binding motif conserved in the IS4 family. Additionally, ISAba11 family members were associated with either no flanking direct repeat (DR) or an ISAba11-typical 5-bp DR and possessed variable-length terminal inverted repeats that exhibited extensive intrafamily sequence identity. Given the limited pairwise identity among TnpISAba11 homologs and the observed restricted distribution of ISAba11, we propose that substantial gaps persist in the evolutionary record of ISAba11 and that this element represents a recent though potentially highly significant entrant into the A. baumannii gene pool. PMID:22081580

  13. Comparative analysis of P450 signature motifs EXXR and CXG in the large and diverse kingdom of fungi: identification of evolutionarily conserved amino acid patterns characteristic of P450 family.

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    Khajamohiddin Syed

    Full Text Available Cytochrome P450 monooxygenases (P450s are heme-thiolate proteins distributed across the biological kingdoms. P450s are catalytically versatile and play key roles in organisms primary and secondary metabolism. Identification of P450s across the biological kingdoms depends largely on the identification of two P450 signature motifs, EXXR and CXG, in the protein sequence. Once a putative protein has been identified as P450, it will be assigned to a family and subfamily based on the criteria that P450s within a family share more than 40% homology and members of subfamilies share more than 55% homology. However, to date, no evidence has been presented that can distinguish members of a P450 family. Here, for the first time we report the identification of EXXR- and CXG-motifs-based amino acid patterns that are characteristic of the P450 family. Analysis of P450 signature motifs in the under-explored fungal P450s from four different phyla, ascomycota, basidiomycota, zygomycota and chytridiomycota, indicated that the EXXR motif is highly variable and the CXG motif is somewhat variable. The amino acids threonine and leucine are preferred as second and third amino acids in the EXXR motif and proline and glycine are preferred as second and third amino acids in the CXG motif in fungal P450s. Analysis of 67 P450 families from biological kingdoms such as plants, animals, bacteria and fungi showed conservation of a set of amino acid patterns characteristic of a particular P450 family in EXXR and CXG motifs. This suggests that during the divergence of P450 families from a common ancestor these amino acids patterns evolve and are retained in each P450 family as a signature of that family. The role of amino acid patterns characteristic of a P450 family in the structural and/or functional aspects of members of the P450 family is a topic for future research.

  14. Evolution of the Twist Subfamily Vertebrate Proteins: Discovery of a Signature Motif and Origin of the Twist1 Glycine-Rich Motifs in the Amino-Terminus Disordered Domain.

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    Yacidzohara Rodriguez

    Full Text Available Twist proteins belong to the basic helix-loop-helix (bHLH family of multifunctional transcriptional factors. These factors are known to use domains other than the common bHLH in protein-protein interactions. There has been much work characterizing the bHLH domain and the C-terminus in protein-protein interactions but despite a few attempts more focus is needed at the N-terminus. Since the region of highest diversity in Twist proteins is the N-terminus, we analyzed the conservation of this region in different vertebrate Twist proteins and study the sequence differences between Twist1 and Twist2 with emphasis on the glycine-rich regions found in Twist1. We found a highly conserved sequence motif in all Twist1 (SSSPVSPADDSLSNSEEE and Twist2 (SSSPVSPVDSLGTSEEE mammalian species with unknown function. Through sequence comparison we demonstrate that the Twist protein family ancestor was "Twist2-like" and the two glycine-rich regions found in Twist1 sequences were acquired late in evolution, apparently not at the same time. The second glycine-rich region started developing first in the fish vertebrate group, while the first glycine region arose afterwards within the reptiles. Disordered domain and secondary structure predictions showed that the amino acid sequence and disorder feature found at the N-terminus is highly evolutionary conserved and could be a functional site that interacts with other proteins. Detailed examination of the glycine-rich regions in the N-terminus of Twist1 demonstrate that the first region is completely aliphatic while the second region contains some polar residues that could be subject to post-translational modification. Phylogenetic and sequence space analysis showed that the Twist1 subfamily is the result of a gene duplication during Twist2 vertebrate fish evolution, and has undergone more evolutionary drift than Twist2. We identified a new signature motif that is characteristic of each Twist paralog and identified

  15. Evolution of the Twist Subfamily Vertebrate Proteins: Discovery of a Signature Motif and Origin of the Twist1 Glycine-Rich Motifs in the Amino-Terminus Disordered Domain.

    Science.gov (United States)

    Rodriguez, Yacidzohara; Gonzalez-Mendez, Ricardo R; Cadilla, Carmen L

    2016-01-01

    Twist proteins belong to the basic helix-loop-helix (bHLH) family of multifunctional transcriptional factors. These factors are known to use domains other than the common bHLH in protein-protein interactions. There has been much work characterizing the bHLH domain and the C-terminus in protein-protein interactions but despite a few attempts more focus is needed at the N-terminus. Since the region of highest diversity in Twist proteins is the N-terminus, we analyzed the conservation of this region in different vertebrate Twist proteins and study the sequence differences between Twist1 and Twist2 with emphasis on the glycine-rich regions found in Twist1. We found a highly conserved sequence motif in all Twist1 (SSSPVSPADDSLSNSEEE) and Twist2 (SSSPVSPVDSLGTSEEE) mammalian species with unknown function. Through sequence comparison we demonstrate that the Twist protein family ancestor was "Twist2-like" and the two glycine-rich regions found in Twist1 sequences were acquired late in evolution, apparently not at the same time. The second glycine-rich region started developing first in the fish vertebrate group, while the first glycine region arose afterwards within the reptiles. Disordered domain and secondary structure predictions showed that the amino acid sequence and disorder feature found at the N-terminus is highly evolutionary conserved and could be a functional site that interacts with other proteins. Detailed examination of the glycine-rich regions in the N-terminus of Twist1 demonstrate that the first region is completely aliphatic while the second region contains some polar residues that could be subject to post-translational modification. Phylogenetic and sequence space analysis showed that the Twist1 subfamily is the result of a gene duplication during Twist2 vertebrate fish evolution, and has undergone more evolutionary drift than Twist2. We identified a new signature motif that is characteristic of each Twist paralog and identified important residues within

  16. The cholesterol-dependent cytolysin signature motif: a critical element in the allosteric pathway that couples membrane binding to pore assembly.

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    Kelley J Dowd

    Full Text Available The cholesterol-dependent cytolysins (CDCs constitute a family of pore-forming toxins that contribute to the pathogenesis of a large number of Gram-positive bacterial pathogens.The most highly conserved region in the primary structure of the CDCs is the signature undecapeptide sequence (ECTGLAWEWWR. The CDC pore forming mechanism is highly sensitive to changes in its structure, yet its contribution to the molecular mechanism of the CDCs has remained enigmatic. Using a combination of fluorescence spectroscopic methods we provide evidence that shows the undecapeptide motif of the archetype CDC, perfringolysin O (PFO, is a key structural element in the allosteric coupling of the cholesterol-mediated membrane binding in domain 4 (D4 to distal structural changes in domain 3 (D3 that are required for the formation of the oligomeric pore complex. Loss of the undecapeptide function prevents all measurable D3 structural transitions, the intermolecular interaction of membrane bound monomers and the assembly of the oligomeric pore complex. We further show that this pathway does not exist in intermedilysin (ILY, a CDC that exhibits a divergent undecapeptide and that has evolved to use human CD59 rather than cholesterol as its receptor. These studies show for the first time that the undecapeptide of the cholesterol-binding CDCs forms a critical element of the allosteric pathway that controls the assembly of the pore complex.

  17. The p53 target Wig-1 regulates p53 mRNA stability through an AU-rich element

    DEFF Research Database (Denmark)

    Vilborg, Anna; Glahder, Jacob-Andreas Harald; Wilhelm, Margareta T

    2009-01-01

    The p53 target gene Wig-1 encodes a double-stranded-RNA-binding zinc finger protein. We show here that Wig-1 binds to p53 mRNA and stabilizes it through an AU-rich element (ARE) in the 3' UTR of the p53 mRNA. This effect is mirrored by enhanced p53 protein levels in both unstressed cells and cells...... exposed to p53-activating stress agents. Thus, the p53 target Wig-1 is a previously undescribed ARE-regulating protein that acts as a positive feedback regulator of p53, with implications both for the steady-state levels of p53 and for the p53 stress response. Our data reveal a previously undescribed link...... between the tumor suppressor p53 and posttranscriptional gene regulation via AREs in mRNA....

  18. Au@PdOx with a PdOx-rich shell and Au-rich core embedded in Co3O4 nanorods for catalytic combustion of methane.

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    Yang, Nating; Liu, Jingwei; Sun, Yuhan; Zhu, Yan

    2017-02-09

    Au@PdOx with a PdOx-rich shell and Au-rich core nested in Co3O4 nanorods exhibited enhanced catalytic performance in the reaction of methane catalytic combustion, compared to monometallic Pd or Au/Co3O4 nanorods as well as conventional PdAu/Co3O4 nanorods. The superior catalysis of Au@PdOx/Co3O4 nanorods is mainly due to the architectural style of the PdOx-rich shell and Au-rich core, which shows strong interaction of Pd, Au, and Co3O4.

  19. Structural modelling and phylogenetic analyses of PgeIF4A2 (Eukaryotic translation initiation factor) from Pennisetum glaucum reveal signature motifs with a role in stress tolerance and development.

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    Agarwal, Aakrati; Mudgil, Yashwanti; Pandey, Saurabh; Fartyal, Dhirendra; Reddy, Malireddy K

    2016-01-01

    Eukaryotic translation initiation factor 4A (eIF4A) is an indispensable component of the translation machinery and also play a role in developmental processes and stress alleviation in plants and animals. Different eIF4A isoforms are present in the cytosol of the cell, namely, eIF4A1, eIF4A2, and eIF4A3 and their expression is tightly regulated in cap-dependent translation. We revealed the structural model of PgeIF4A2 protein using the crystal structure of Homo sapiens eIF4A3 (PDB ID: 2J0S) as template by Modeller 9.12. The resultant PgeIF4A2 model structure was refined by PROCHECK, ProSA, Verify3D and RMSD that showed the model structure is reliable with 77 % amino acid sequence identity with template. Investigation revealed two conserved signatures for ATP-dependent RNA Helicase DEAD-box conserved site (VLDEADEML) and RNA helicase DEAD-box type, Q-motif in sheet-turn-helix and α-helical region respectively. All these conserved motifs are responsible for response during developmental stages and stress tolerance in plants.

  20. The association of Alu repeats with the generation of potential AU-rich elements (ARE at 3' untranslated regions.

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    Bhak Jonghwa

    2004-12-01

    Full Text Available Abstract Background A significant portion (about 8% in the human genome of mammalian mRNA sequences contains AU (Adenine and Uracil rich elements or AREs at their 3' untranslated regions (UTR. These mRNA sequences are usually stable. However, an increasing number of observations have been made of unstable species, possibly depending on certain elements such as Alu repeats. ARE motifs are repeats of the tetramer AUUU and a monomer A at the end of the repeats ((AUUUnA. The importance of AREs in biology is that they make certain mRNA unstable. Proto-oncogene, such as c-fos, c-myc, and c-jun in humans, are associated with AREs. Although it has been known that the increased number of ARE motifs caused the decrease of the half-life of mRNA containing ARE repeats, the exact mechanism is as of yet unknown. We analyzed the occurrences of AREs and Alu and propose a possible mechanism for how human mRNA could acquire and keep AREs at its 3' UTR originating from Alu repeats. Results Interspersed in the human genome, Alu repeats occupy 5% of the 3' UTR of mRNA sequences. Alu has poly-adenine (poly-A regions at its end, which lead to poly-thymine (poly-T regions at the end of its complementary Alu. It has been found that AREs are present at the poly-T regions. From the 3' UTR of the NCBI's reference mRNA sequence database, we found nearly 40% (38.5% of ARE (Class I were associated with Alu sequences (Table 1 within one mismatch allowance in ARE sequences. Other ARE classes had statistically significant associations as well. This is far from a random occurrence given their limited quantity. At each ARE class, random distribution was simulated 1,000 times, and it was shown that there is a special relationship between ARE patterns and the Alu repeats. Table 1 Defined ARE classes. (Symbol marks are used in this study instead of full sequences. Symbol ARE sequence Class I (AUUU5A AUUUAUUUAUUUAUUUAUUUA Class II (AUUU4A AUUUAUUUAUUUAUUUA Class III U(AUUU3AU

  1. FastMotif: spectral sequence motif discovery

    National Research Council Canada - National Science Library

    Colombo, Nicoló; Vlassis, Nikos

    2015-01-01

    ... datasets produced by modern high-throughput sequencing technologies. We present FastMotif, a new motif discovery algorithm that is built on a recent machine learning technique referred to as Method of Moments...

  2. Origin of Zn-Pb-Sb-Au mineralization adjacent to the Paleoproterozoic Boliden Au-rich VMS deposit, Sweden: evidence from petrographic and oxygen isotope characteristics

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    Adomako-Ansah, Kofi; Ishiyama, Daizo; Allen, Rodney

    2017-10-01

    Adjacent to the world-class Boliden deposit, fine- to coarse-grained Zn-Pb-Sb-Au-rich sulfide-sulfosalt-bearing horizons occur within the base of a metasedimentary succession that has previously been regarded to stratigraphically overlie the Skellefte Volcanics and Boliden deposit. The metasedimentary succession comprises interbedded mudstone and normal-graded crystal-rich volcanic sandstone-siltstone units, interpreted to be low-density turbidity currents in a subaqueous environment below wave base. The sharp contact between the mineralized intervals and volcanic sandstone is concordant to the bedding planes and compaction foliation. Above and below the mineralization, the wall rocks contain well-preserved plagioclase crystals, partly enclosed by a weak alteration composed of bedding-parallel metamorphic biotite±sericite minerals. These observations are consistent with burial (or tectonic) compaction and diagenetic alteration that was overprinted by metamorphic biotite. The occurrence of biotite in the wall rocks and homogenization recrystallization of the sulfide-sulfosalt assemblage in the mineralized intervals are consistent with peak metamorphic conditions ( 350-450 °C, < 4 kbars) in the Boliden area. However, preservation of plagioclase and water-rock interaction under rock-dominant conditions suggest that high δ18O values (+ 10.7 to + 13.5‰) acquired during diagenesis were unchanged by the metamorphic overprint. The δ18O values yield low temperatures (< 150 °C), which indicate pre-metamorphic conditions. These data suggest that the Zn-Pb-Sb-Au-rich intervals formed as pre-metamorphic distal syn-volcanic exhalative mineralization during sedimentation of the Vargfors group metasedimentary rocks. This implies that massive sulfide formation continued even during Vargfors group time and, therefore, there is still potential for discovery of gold-rich base-metal ores in this part of the Skellefte field stratigraphy.

  3. Pengembangan Motif Batik Khas Bali

    Directory of Open Access Journals (Sweden)

    Irfa'ina Rohana Salma

    2016-04-01

    Full Text Available ABSTRAKIndustri batik berkembang pesat di Bali, namun motif-motif batiknya tidak mencerminkan identitas khas daerah. Oleh karena itu perlu diciptakan desain motif batik khas Bali yang sumber inspirasinya digali budaya dan alam Bali. Tujuan penelitian dan penciptaan seni ini adalah untuk menghasilkan motif batik yang mempunyai bentuk  unik dan karakteristik sehingga dapat mencerminkan budaya dan alam Bali. Metode yang digunakan yaitu pengumpulan data, perancangan motif, perwujudan menjadi batik, serta uji estetikanya. Dari penciptaan seni ini berhasil diciptakan 5 motif batik yaitu: (1 Motif Jepun Alit; (2 Motif Jepun Ageng; (3 Motif Sekar Jagad Bali; (4 Motif Teratai Banji; dan (5 Motif Poleng Biru. Berdasarkan hasil penilaian “Selera Estetika” diketahui bahwa motif yang paling banyak disukai adalah Motif Jepun Alit, Motif Sekar Jagad Bali,  dan Motif Teratai Banji. Kata kunci: Motif Jepun Alit, Motif Jepun Ageng, Motif Sekar Jagad Bali, Motif Teratai Banji, Motif Poleng Biru ABSTRACT Batik industry is growing rapidly in Bali, but its batik motifs do not reflect the typical regional identities. Therefore, it is necessary to create a distinctive design motif source of Bali excavated  from the repertoire of traditional Balinese arts and culture. The purpose of this research and its art creation is to produce batik motifs that have a unique shape and characteristics  to reflect the Balinese culture and natural surroundings. The method used by gathering and collecting data, designing motifs to  become the embodiment of batik. From the creation of this art had been created 5 motifs, namely: (1 Motif Jepun Alit; (2 Motif Jepun Ageng; (3 Motif Sekar Jagad Bali; (4 Motif Teratai Banji; and (5 Motif Poleng Biru. Based on the results of aesthetical assessment known that the most preferred motif are  Motif Jepun Alit, Motif Sekar Jagad Bali, and Motif Teratai Banji. Key words: Motif Jepun Alit, Motif Jepun Ageng, Motif Sekar Jagad Bali, Motif

  4. Mining Conditional Phosphorylation Motifs.

    Science.gov (United States)

    Liu, Xiaoqing; Wu, Jun; Gong, Haipeng; Deng, Shengchun; He, Zengyou

    2014-01-01

    Phosphorylation motifs represent position-specific amino acid patterns around the phosphorylation sites in the set of phosphopeptides. Several algorithms have been proposed to uncover phosphorylation motifs, whereas the problem of efficiently discovering a set of significant motifs with sufficiently high coverage and non-redundancy still remains unsolved. Here we present a novel notion called conditional phosphorylation motifs. Through this new concept, the motifs whose over-expressiveness mainly benefits from its constituting parts can be filtered out effectively. To discover conditional phosphorylation motifs, we propose an algorithm called C-Motif for a non-redundant identification of significant phosphorylation motifs. C-Motif is implemented under the Apriori framework, and it tests the statistical significance together with the frequency of candidate motifs in a single stage. Experiments demonstrate that C-Motif outperforms some current algorithms such as MMFPh and Motif-All in terms of coverage and non-redundancy of the results and efficiency of the execution. The source code of C-Motif is available at: https://sourceforge. net/projects/cmotif/.

  5. Analysis of the A-U rich hairpin from the intergenic region of tospovirus S RNA as target and inducer of RNA silencing.

    Directory of Open Access Journals (Sweden)

    Marcio Hedil

    Full Text Available Earlier work indicated that Tomato spotted wilt virus (TSWV messenger transcripts, and not the (antigenomic RNAs, are targeted by the RNA silencing machinery. Here, the predicted AU-rich hairpin (HP structure encoded by the intergenic region (IGR of the TSWV S RNA, and present at the 3' end of viral mRNAs, was analyzed as a target and inducer for RNA silencing. Virus-derived siRNAs (vsiRNAs purified from virus infected plants were found to derive from all three genomic RNA segments but predominantly the ambisense M and S RNAs. Further profiling on the S RNA sequence revealed that vsiRNAs were found from almost the entire S RNA sequence, except the IGR from where hardly any vsiRNAs were found. Similar profiles were observed with the distantly related Tomato yellow ring tospovirus (TYRV. Dicer cleavage assays using Drosophila melanogaster (Dm embryo extracts showed that synthetic transcripts of the IGR-HP region were recognized as substrate for Dicer. Transient agroinfiltration assays of a GFP-sensor construct containing the IGR-HP sequence at its 3' UTR (GFP-HP did not show more rapid/strong silencing and profiling of the corresponding siRNAs, generated outside the context of a viral infection, still revealed relatively low levels of IGR-HP-derived siRNAs. These data support the idea that the IGR-HP is a weak inducer of RNA silencing and only plays a minor role in the amplification of a strong antiviral RNAi response.

  6. FastMotif: spectral sequence motif discovery.

    Science.gov (United States)

    Colombo, Nicoló; Vlassis, Nikos

    2015-08-15

    Sequence discovery tools play a central role in several fields of computational biology. In the framework of Transcription Factor binding studies, most of the existing motif finding algorithms are computationally demanding, and they may not be able to support the increasingly large datasets produced by modern high-throughput sequencing technologies. We present FastMotif, a new motif discovery algorithm that is built on a recent machine learning technique referred to as Method of Moments. Based on spectral decompositions, our method is robust to model misspecifications and is not prone to locally optimal solutions. We obtain an algorithm that is extremely fast and designed for the analysis of big sequencing data. On HT-Selex data, FastMotif extracts motif profiles that match those computed by various state-of-the-art algorithms, but one order of magnitude faster. We provide a theoretical and numerical analysis of the algorithm's robustness and discuss its sensitivity with respect to the free parameters. The Matlab code of FastMotif is available from http://lcsb-portal.uni.lu/bioinformatics. vlassis@adobe.com Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  7. Efficient exact motif discovery.

    Science.gov (United States)

    Marschall, Tobias; Rahmann, Sven

    2009-06-15

    The motif discovery problem consists of finding over-represented patterns in a collection of biosequences. It is one of the classical sequence analysis problems, but still has not been satisfactorily solved in an exact and efficient manner. This is partly due to the large number of possibilities of defining the motif search space and the notion of over-representation. Even for well-defined formalizations, the problem is frequently solved in an ad hoc manner with heuristics that do not guarantee to find the best motif. We show how to solve the motif discovery problem (almost) exactly on a practically relevant space of IUPAC generalized string patterns, using the p-value with respect to an i.i.d. model or a Markov model as the measure of over-representation. In particular, (i) we use a highly accurate compound Poisson approximation for the null distribution of the number of motif occurrences. We show how to compute the exact clump size distribution using a recently introduced device called probabilistic arithmetic automaton (PAA). (ii) We define two p-value scores for over-representation, the first one based on the total number of motif occurrences, the second one based on the number of sequences in a collection with at least one occurrence. (iii) We describe an algorithm to discover the optimal pattern with respect to either of the scores. The method exploits monotonicity properties of the compound Poisson approximation and is by orders of magnitude faster than exhaustive enumeration of IUPAC strings (11.8 h compared with an extrapolated runtime of 4.8 years). (iv) We justify the use of the proposed scores for motif discovery by showing our method to outperform other motif discovery algorithms (e.g. MEME, Weeder) on benchmark datasets. We also propose new motifs on Mycobacterium tuberculosis. The method has been implemented in Java. It can be obtained from http://ls11-www.cs.tu-dortmund.de/people/marschal/paa_md/.

  8. ELECTRONIC SIGNATURES

    African Journals Online (AJOL)

    10332324

    'electronic signature' means data attached to, incorporated in, or logically associated with other data and which is intended by the user to serve as a signature;. The suggested new definition for an electronic signature reads as follows: 'electronic signature' means a sound, symbol or process that is (i) uniquely linked to the ...

  9. Crystal Structure of the N-Terminal RNA Recognition Motif of mRNA Decay Regulator AUF1

    Directory of Open Access Journals (Sweden)

    Young Jun Choi

    2016-01-01

    Full Text Available AU-rich element binding/degradation factor 1 (AUF1 plays a role in destabilizing mRNAs by forming complexes with AU-rich elements (ARE in the 3′-untranslated regions. Multiple AUF1-ARE complexes regulate the translation of encoded products related to the cell cycle, apoptosis, and inflammation. AUF1 contains two tandem RNA recognition motifs (RRM and a Gln- (Q- rich domain in their C-terminal region. To observe how the two RRMs are involved in recognizing ARE, we obtained the AUF1-p37 protein covering the two RRMs. However, only N-terminal RRM (RRM1 was crystallized and its structure was determined at 1.7 Å resolution. It appears that the RRM1 and RRM2 separated before crystallization. To demonstrate which factors affect the separate RRM1-2, we performed limited proteolysis using trypsin. The results indicated that the intact proteins were cleaved by unknown proteases that were associated with them prior to crystallization. In comparison with each of the monomers, the conformations of the β2-β3 loops were highly variable. Furthermore, a comparison with the RRM1-2 structures of HuR and hnRNP A1 revealed that a dimer of RRM1 could be one of the possible conformations of RRM1-2. Our data may provide a guidance for further structural investigations of AUF1 tandem RRM repeat and its mode of ARE binding.

  10. Visibility graph motifs

    CERN Document Server

    Iacovacci, Jacopo

    2015-01-01

    Visibility algorithms transform time series into graphs and encode dynamical information in their topology, paving the way for graph-theoretical time series analysis as well as building a bridge between nonlinear dynamics and network science. In this work we introduce and study the concept of visibility graph motifs, smaller substructures that appear with characteristic frequencies. We develop a theory to compute in an exact way the motif profiles associated to general classes of deterministic and stochastic dynamics. We find that this simple property is indeed a highly informative and computationally efficient feature capable to distinguish among different dynamics and robust against noise contamination. We finally confirm that it can be used in practice to perform unsupervised learning, by extracting motif profiles from experimental heart-rate series and being able, accordingly, to disentangle meditative from other relaxation states. Applications of this general theory include the automatic classification a...

  11. The MHC motif viewer

    DEFF Research Database (Denmark)

    Rapin, Nicolas Philippe Jean-Pierre; Hoof, Ilka; Lund, Ole

    2010-01-01

    In vertebrates, the onset of cellular immune reactions is controlled by presentation of peptides in complex with major histocompatibility complex (MHC) molecules to T cell receptors. In humans, MHCs are called human leukocyte antigens (HLAs). Different MHC molecules present different subsets...... is hampered by the lack of tools for browsing and comparing specificity of these molecules. We have developed a Web server, MHC Motif Viewer, which allows the display of the binding motif for MHC class I proteins for human, chimpanzee, rhesus monkey, mouse, and swine, as well as HLA-DR protein sequences...

  12. MHC motif viewer

    DEFF Research Database (Denmark)

    Rapin, Nicolas Philippe Jean-Pierre; Hoof, Ilka; Lund, Ole

    2008-01-01

    viewer, that allows the display of the likely binding motif for all human class I proteins of the loci HLA A, B, C, and E and for MHC class I molecules from chimpanzee (Pan troglodytes), rhesus monkey (Macaca mulatta), and mouse (Mus musculus). Furthermore, it covers all HLA-DR protein sequences...

  13. Fingerprint motifs of phytases

    African Journals Online (AJOL)

    Fan CM

    2013-03-06

    Mar 6, 2013 ... unique sequences including 131 prokaryotic and 102 eukaryotic phytase sequences covered phytases from. 190 species including 131 bacterium sequences, 70 fungus sequences, 27 plant sequences, one animal sequence and four yeast sequences. For motif analysis, 54 sequences were randomly.

  14. [Personal motif in art].

    Science.gov (United States)

    Gerevich, József

    2015-01-01

    One of the basic questions of the art psychology is whether a personal motif is to be found behind works of art and if so, how openly or indirectly it appears in the work itself. Analysis of examples and documents from the fine arts and literature allow us to conclude that the personal motif that can be identified by the viewer through symbols, at times easily at others with more difficulty, gives an emotional plus to the artistic product. The personal motif may be found in traumatic experiences, in communication to the model or with other emotionally important persons (mourning, disappointment, revenge, hatred, rivalry, revolt etc.), in self-searching, or self-analysis. The emotions are expressed in artistic activity either directly or indirectly. The intention nourished by the artist's identity (Kunstwollen) may stand in the way of spontaneous self-expression, channelling it into hidden paths. Under the influence of certain circumstances, the artist may arouse in the viewer, consciously or unconsciously, an illusionary, misleading image of himself. An examination of the personal motif is one of the important research areas of art therapy.

  15. ActiveMotif: Interactive motif discovery with human feedback.

    Science.gov (United States)

    Younghoon Kim; Woonghee Lee; Keonwoo Kim

    2017-07-01

    Motif detection, which is to discover short patterns involved in many important biological processes, has been recently raised as an important task in bioinformatics. The traditional algorithms to find a sequence motif have been developed using machine learning only without involving the experience and domain knowledge of human experts effectively. In this paper, we propose an interactive motif discovery system by introducing a new learning algorithm, by generalizing a well-known statistical motif model, whose inference can be shepherded by human feedback.

  16. Topological generalizations of network motifs

    Science.gov (United States)

    Kashtan, N.; Itzkovitz, S.; Milo, R.; Alon, U.

    2004-09-01

    Biological and technological networks contain patterns, termed network motifs, which occur far more often than in randomized networks. Network motifs were suggested to be elementary building blocks that carry out key functions in the network. It is of interest to understand how network motifs combine to form larger structures. To address this, we present a systematic approach to define “motif generalizations”: families of motifs of different sizes that share a common architectural theme. To define motif generalizations, we first define “roles” in a subgraph according to structural equivalence. For example, the feedforward loop triad—a motif in transcription, neuronal, and some electronic networks—has three roles: an input node, an output node, and an internal node. The roles are used to define possible generalizations of the motif. The feedforward loop can have three simple generalizations, based on replicating each of the three roles and their connections. We present algorithms for efficiently detecting motif generalizations. We find that the transcription networks of bacteria and yeast display only one of the three generalizations, the multi-output feedforward generalization. In contrast, the neuronal network of C. elegans mainly displays the multi-input generalization. Forward-logic electronic circuits display a multi-input, multi-output hybrid. Thus, networks which share a common motif can have very different generalizations of that motif. Using mathematical modeling, we describe the information processing functions of the different motif generalizations in transcription, neuronal, and electronic networks.

  17. Structural alphabet motif discovery and a structural motif database.

    Science.gov (United States)

    Ku, Shih-Yen; Hu, Yuh-Jyh

    2012-01-01

    This study proposes a general framework for structural motif discovery. The framework is based on a modular design in which the system components can be modified or replaced independently to increase its applicability to various studies. It is a two-stage approach that first converts protein 3D structures into structural alphabet sequences, and then applies a sequence motif-finding tool to these sequences to detect conserved motifs. We named the structural motif database we built the SA-Motifbase, which provides the structural information conserved at different hierarchical levels in SCOP. For each motif, SA-Motifbase presents its 3D view; alphabet letter preference; alphabet letter frequency distribution; and the significance. SA-Motifbase is available at http://bioinfo.cis.nctu.edu.tw/samotifbase/. Copyright © 2011 Elsevier Ltd. All rights reserved.

  18. 3'UTR AU-Rich Elements (AREs) and the RNA-Binding Protein Tristetraprolin (TTP) Are Not Required for the LPS-Mediated Destabilization of Phospholipase-Cβ-2 mRNA in Murine Macrophages.

    Science.gov (United States)

    Shukla, Smita; Elson, Genie; Blackshear, Perry J; Lutz, Carol S; Leibovich, S Joseph

    2017-04-01

    We have shown previously that bacterial lipopolysaccharide (LPS)-mediated suppression of phospholipase-Cβ-2 (PLCβ-2) expression is involved in M1 (inflammatory) to M2-like (wound healing) phenotypic switching of macrophages triggered by adenosine. This suppression is mediated post-transcriptionally by destabilization of PLCβ-2 mRNA (messenger ribonucleic acid). To investigate the mechanism of this LPS-mediated destabilization, we examined the roles of RNA-binding agents including microRNAs and RNA-binding proteins that are involved in regulating stability of mRNAs encoding growth factors, inflammatory mediators, and proto-oncogenes. Adenylate and uridylate (AU)-rich elements (AREs) in 3'UTRs are specific recognition sites for RNA-binding proteins including tristetraprolin (TTP), HuR, and AUF1 and for microRNAs that are involved in regulating mRNA stability. In this study, we investigated the role of TTP and AREs in regulating PLCβ-2 mRNA stability. The 3'UTR of the PLCβ-2 gene was inserted into the pLightswitch luciferase reporter plasmid and transfected into RAW264.7 cells. LPS suppressed luciferase expression from this reporter. Luciferase expression from mutant 3'UTR constructs lacking AREs was similarly downregulated, suggesting that these regions are not required for LPS-mediated suppression of PLCβ-2. TTP was rapidly upregulated in both primary murine macrophages and RAW264.7 cells in response to LPS. Suppression of PLCβ-2 by LPS was examined using macrophages from mice lacking TTP (TTP(-/-)). LPS suppressed PLCβ-2 expression to the same extent in wild type (WT) and TTP(-/-) macrophages. Also, the rate of decay of PLCβ-2 mRNA in LPS-treated macrophages following transcriptional blockade was similar in WT and TTP(-/-) macrophages, clearly indicating that TTP is not involved in LPS-mediated destabilization of PLCβ-2 mRNA in macrophages.

  19. Genome-wide map of RNA degradation kinetics patterns in dendritic cells after LPS stimulation facilitates identification of primary sequence and secondary structure motifs in mRNAs.

    Science.gov (United States)

    Kumagai, Yutaro; Vandenbon, Alexis; Teraguchi, Shunsuke; Akira, Shizuo; Suzuki, Yutaka

    2016-12-22

    Immune cells have to change their gene expression patterns dynamically in response to external stimuli such as lipopolysaccharide (LPS). The gene expression is regulated at multiple steps in eukaryotic cells, in which control of RNA levels at both the transcriptional level and the post-transcriptional level plays important role. Impairment of the control leads to aberrant immune responses such as excessive or impaired production of cytokines. However, genome-wide studies focusing on the post-transcriptional control were relatively rare until recently. Moreover, several RNA cis elements and RNA-binding proteins have been found to be involved in the process, but our general understanding remains poor, partly because identification of regulatory RNA motifs is very challenging in spite of its importance. We took advantage of genome-wide measurement of RNA degradation in combination with estimation of degradation kinetics by qualitative approach, and performed de novo prediction of RNA sequence and structure motifs. To classify genes by their RNA degradation kinetics, we first measured RNA degradation time course in mouse dendritic cells after LPS stimulation and the time courses were clustered to estimate degradation kinetics and to find patterns in the kinetics. Then genes were clustered by their similarity in degradation kinetics patterns. The 3' UTR sequences of a cluster was subjected to de novo sequence or structure motif prediction. The quick degradation kinetics was found to be strongly associated with lower gene expression level, immediate regulation (both induction and repression) of gene expression level, and longer 3' UTR length. De novo sequence motif prediction found AU-rich element-like and TTP-binding sequence-like motifs which are enriched in quickly degrading genes. De novo structure motif prediction found a known functional motif, namely stem-loop structure containing sequence bound by RNA-binding protein Roquin and Regnase-1, as well as unknown

  20. A cluster refinement algorithm for motif discovery.

    Science.gov (United States)

    Li, Gang; Chan, Tak-Ming; Leung, Kwong-Sak; Lee, Kin-Hong

    2010-01-01

    Finding Transcription Factor Binding Sites, i.e., motif discovery, is crucial for understanding the gene regulatory relationship. Motifs are weakly conserved and motif discovery is an NP-hard problem. We propose a new approach called Cluster Refinement Algorithm for Motif Discovery (CRMD). CRMD employs a flexible statistical motif model allowing a variable number of motifs and motif instances. CRMD first uses a novel entropy-based clustering to find complete and good starting candidate motifs from the DNA sequences. CRMD then employs an effective greedy refinement to search for optimal motifs from the candidate motifs. The refinement is fast, and it changes the number of motif instances based on the adaptive thresholds. The performance of CRMD is further enhanced if the problem has one occurrence of motif instance per sequence. Using an appropriate similarity test of motifs, CRMD is also able to find multiple motifs. CRMD has been tested extensively on synthetic and real data sets. The experimental results verify that CRMD usually outperforms four other state-of-the-art algorithms in terms of the qualities of the solutions with competitive computing time. It finds a good balance between finding true motif instances and screening false motif instances, and is robust on problems of various levels of difficulty.

  1. Unravelling daily human mobility motifs.

    Science.gov (United States)

    Schneider, Christian M; Belik, Vitaly; Couronné, Thomas; Smoreda, Zbigniew; González, Marta C

    2013-07-06

    Human mobility is differentiated by time scales. While the mechanism for long time scales has been studied, the underlying mechanism on the daily scale is still unrevealed. Here, we uncover the mechanism responsible for the daily mobility patterns by analysing the temporal and spatial trajectories of thousands of persons as individual networks. Using the concept of motifs from network theory, we find only 17 unique networks are present in daily mobility and they follow simple rules. These networks, called here motifs, are sufficient to capture up to 90 per cent of the population in surveys and mobile phone datasets for different countries. Each individual exhibits a characteristic motif, which seems to be stable over several months. Consequently, daily human mobility can be reproduced by an analytically tractable framework for Markov chains by modelling periods of high-frequency trips followed by periods of lower activity as the key ingredient.

  2. Biological network motif detection and evaluation.

    Science.gov (United States)

    Kim, Wooyoung; Li, Min; Wang, Jianxin; Pan, Yi

    2011-01-01

    Molecular level of biological data can be constructed into system level of data as biological networks. Network motifs are defined as over-represented small connected subgraphs in networks and they have been used for many biological applications. Since network motif discovery involves computationally challenging processes, previous algorithms have focused on computational efficiency. However, we believe that the biological quality of network motifs is also very important. We define biological network motifs as biologically significant subgraphs and traditional network motifs are differentiated as structural network motifs in this paper. We develop five algorithms, namely, EDGEGO-BNM, EDGEBETWEENNESS-BNM, NMF-BNM, NMFGO-BNM and VOLTAGE-BNM, for efficient detection of biological network motifs, and introduce several evaluation measures including motifs included in complex, motifs included in functional module and GO term clustering score in this paper. Experimental results show that EDGEGO-BNM and EDGEBETWEENNESS-BNM perform better than existing algorithms and all of our algorithms are applicable to find structural network motifs as well. We provide new approaches to finding network motifs in biological networks. Our algorithms efficiently detect biological network motifs and further improve existing algorithms to find high quality structural network motifs, which would be impossible using existing algorithms. The performances of the algorithms are compared based on our new evaluation measures in biological contexts. We believe that our work gives some guidelines of network motifs research for the biological networks.

  3. Biological network motif detection and evaluation

    Directory of Open Access Journals (Sweden)

    Kim Wooyoung

    2011-12-01

    Full Text Available Abstract Background Molecular level of biological data can be constructed into system level of data as biological networks. Network motifs are defined as over-represented small connected subgraphs in networks and they have been used for many biological applications. Since network motif discovery involves computationally challenging processes, previous algorithms have focused on computational efficiency. However, we believe that the biological quality of network motifs is also very important. Results We define biological network motifs as biologically significant subgraphs and traditional network motifs are differentiated as structural network motifs in this paper. We develop five algorithms, namely, EDGEGO-BNM, EDGEBETWEENNESS-BNM, NMF-BNM, NMFGO-BNM and VOLTAGE-BNM, for efficient detection of biological network motifs, and introduce several evaluation measures including motifs included in complex, motifs included in functional module and GO term clustering score in this paper. Experimental results show that EDGEGO-BNM and EDGEBETWEENNESS-BNM perform better than existing algorithms and all of our algorithms are applicable to find structural network motifs as well. Conclusion We provide new approaches to finding network motifs in biological networks. Our algorithms efficiently detect biological network motifs and further improve existing algorithms to find high quality structural network motifs, which would be impossible using existing algorithms. The performances of the algorithms are compared based on our new evaluation measures in biological contexts. We believe that our work gives some guidelines of network motifs research for the biological networks.

  4. MEET: motif elements estimation toolkit.

    Science.gov (United States)

    Pairó, Erola; Maynou, Joan; Vallverdú, Montserrat; Caminal, Pere; Marco, Santiago; Perera, Alexandre

    2011-01-01

    MEET is an R package that integrates a set of algorithms for the detection of transcription factor binding sites (TFBS). The MEET R package includes five motif searching algorithms: MEME/MAST(Multiple Expectation-Maximization for Motif Elicitation), Q-residuals, MDscan (Motif Discovery scan), ITEME (Information Theory Elements for Motif Estimation) and MATCH. In addition MEET allows the user to work with different alignment algorithms: MUSCLE (Multiple Sequence Comparison by Log-Expectation), ClustalW and MEME. The package can work in two modes, training and detection. The training mode allows the user to choose the best parameters of a detector. Once the parameters are chosen, the detection mode allows to analyze a genome looking for binding sites. Both modes can combine the different alignment and detection methods, offering multiple possibilities. Combining the alignments and the detection algorithms makes possible the comparison between detection models at the same level, without having to care about the differences produced during the alignment process. The MEET R package can be downloaded from http://sisbio.recerca.upc.edu/R/MEET_1.0. tar.gz.

  5. Predicting conserved protein motifs with Sub-HMMs

    Directory of Open Access Journals (Sweden)

    Girke Thomas

    2010-04-01

    Full Text Available Abstract Background Profile HMMs (hidden Markov models provide effective methods for modeling the conserved regions of protein families. A limitation of the resulting domain models is the difficulty to pinpoint their much shorter functional sub-features, such as catalytically relevant sequence motifs in enzymes or ligand binding signatures of receptor proteins. Results To identify these conserved motifs efficiently, we propose a method for extracting the most information-rich regions in protein families from their profile HMMs. The method was used here to predict a comprehensive set of sub-HMMs from the Pfam domain database. Cross-validations with the PROSITE and CSA databases confirmed the efficiency of the method in predicting most of the known functionally relevant motifs and residues. At the same time, 46,768 novel conserved regions could be predicted. The data set also allowed us to link at least 461 Pfam domains of known and unknown function by their common sub-HMMs. Finally, the sub-HMM method showed very promising results as an alternative search method for identifying proteins that share only short sequence similarities. Conclusions Sub-HMMs extend the application spectrum of profile HMMs to motif discovery. Their most interesting utility is the identification of the functionally relevant residues in proteins of known and unknown function. Additionally, sub-HMMs can be used for highly localized sequence similarity searches that focus on shorter conserved features rather than entire domains or global similarities. The motif data generated by this study is a valuable knowledge resource for characterizing protein functions in the future.

  6. Relinkable Ring Signature

    Science.gov (United States)

    Suzuki, Koutarou; Hoshino, Fumitaka; Kobayashi, Tetsutaro

    In this paper, we propose the concept of a relinkable ring signature, which is a ring signature with ring reformation function, i.e., a signer can delegate ring reformation ability separately from signing ability to his/her proxy. The relinkable ring signature can be applicable to proxy ring reformation, anonymization of past-generated signature, or ring signature for dynamic group. We also propose a concrete relinkable ring signature scheme that uses pairing in the random oracle model.

  7. Motif discovery in ranked lists of sequences

    DEFF Research Database (Denmark)

    Nielsen, Morten Muhlig; Tataru, Paula; Madsen, Tobias

    2016-01-01

    . These features make Regmex well suited for a range of biological sequence analysis problems related to motif discovery, exemplified by microRNA seed enrichment, but also including enrichment problems involving complex motifs and combinations of motifs. We demonstrate a number of usage scenarios that take......Motif analysis has long been an important method to characterize biological functionality and the current growth of sequencing-based genomics experiments further extends its potential. These diverse experiments often generate sequence lists ranked by some functional property. There is therefore...... a growing need for motif analysis methods that can exploit this coupled data structure and be tailored for specific biological questions. Here, we present an exploratory motif analysis tool, Regmex (REGular expression Motif EXplorer), which offers several methods to evaluate the correlation of motifs...

  8. MODIS: an audio motif discovery software

    OpenAIRE

    Catanese, Laurence; Souviraà-Labastie, Nathan; Qu, Bingqing; Campion, Sébastien; Gravier, Guillaume; Vincent, Emmanuel; Bimbot, Frédéric

    2013-01-01

    International audience; MODIS is a free speech and audio motif discovery software developed at IRISA Rennes. Motif discovery is the task of discovering and collecting occurrences of repeating patterns in the absence of prior knowledge, or training material. MODIS is based on a generic approach to mine repeating audio sequences, with tolerance to motif variability. The algorithm implementation allows to process large audio streams at a reasonable speed where motif discovery often requires huge...

  9. Global mapping of transcription factor motifs in human aging.

    Science.gov (United States)

    Alfego, David; Rodeck, Ulrich; Kriete, Andres

    2018-01-01

    Biological aging is a complex process dependent on the interplay of cell autonomous and tissue contextual changes which occur in response to cumulative molecular stress and manifest through adaptive transcriptional reprogramming. Here we describe a transcription factor (TF) meta-analysis of gene expression datasets accrued from 18 tissue sites collected at different biological ages and from 7 different in-vitro aging models. In-vitro aging platforms included replicative senescence and an energy restriction model in quiescence (ERiQ), in which ATP was transiently reduced. TF motifs in promoter regions of trimmed sets of target genes were scanned using JASPAR and TRANSFAC. TF signatures established a global mapping of agglomerating motifs with distinct clusters when ranked hierarchically. Remarkably, the ERiQ profile was shared with the majority of in-vivo aged tissues. Fitting motifs in a minimalistic protein-protein network allowed to probe for connectivity to distinct stress sensors. The DNA damage sensors ATM and ATR linked to the subnetwork associated with senescence. By contrast, the energy sensors PTEN and AMPK connected to the nodes in the ERiQ subnetwork. These data suggest that metabolic dysfunction may be linked to transcriptional patterns characteristic of many aged tissues and distinct from cumulative DNA damage associated with senescence.

  10. Developing composite signatures

    Science.gov (United States)

    Hawley, Chadwick T.; Carpenter, Tom; Cappelaere, Patrice G.; Frye, Stu; Lemoigne-Stewart, Jacqueline J.; Mandle, Dan; Montgomery, Sarah; Williams-Bess, Autumn

    2011-06-01

    A composite signature is a group of signatures that are related in such a way to more completely or further define a target or operational endeavor at a higher fidelity. This paper explores the merits of using composite signatures, in lieu of waiting for opportunities for the more elusive diagnostic signatures, to satisfy key essential elements of information Keywords: signature, composite signature, civil disaster (EEI) associated with civil disaster-related problems. It discusses efforts to refine composite signature development methodology and quantify the relative value of composite vs. diagnostic signatures. The objectives are to: 1) investigate and develop innovative composite signatures associated with civil disasters, including physical, chemical and pattern/behavioral; 2) explore the feasibility of collecting representative composite signatures using current and emerging intelligence, surveillance, and reconnaissance (ISR) collection architectures leveraging civilian and commercial architectures; and 3) collaborate extensively with scientists and engineers from U.S. government organizations and laboratories, the defense industry, and academic institutions.

  11. Detecting correlations among functional-sequence motifs

    Science.gov (United States)

    Pirino, Davide; Rigosa, Jacopo; Ledda, Alice; Ferretti, Luca

    2012-06-01

    Sequence motifs are words of nucleotides in DNA with biological functions, e.g., gene regulation. Identification of such words proceeds through rejection of Markov models on the expected motif frequency along the genome. Additional biological information can be extracted from the correlation structure among patterns of motif occurrences. In this paper a log-linear multivariate intensity Poisson model is estimated via expectation maximization on a set of motifs along the genome of E. coli K12. The proposed approach allows for excitatory as well as inhibitory interactions among motifs and between motifs and other genomic features like gene occurrences. Our findings confirm previous stylized facts about such types of interactions and shed new light on genome-maintenance functions of some particular motifs. We expect these methods to be applicable to a wider set of genomic features.

  12. Kopi dan Kakao dalam Kreasi Motif Batik Khas Jember

    Directory of Open Access Journals (Sweden)

    Irfa'ina Rohana Salma

    2015-06-01

    Full Text Available ABSTRAK Batik Jember selama ini identik dengan motif daun tembakau. Visualisasi daun tembakau dalam motif Batik Jember cukup lemah, yaitu kurang berkarakter karena motif yang muncul adalah seperti gambar daun pada umumnya. Oleh karena itu perlu diciptakan desain motif batik khas Jember yang sumber inspirasinya digali dari kekayaan alam lainnya dari Jember yang mempunyai bentuk spesifik dan karakteristik sehingga identitas motif bisa didapatkan dengan lebih kuat. Hasil alam khas Jember tersebut adalah kopi dan kakao. Tujuan penciptaan seni ini adalah untuk menghasilkan motif batik  baru yang mempunyai ciri khas Jember. Metode yang digunakan yaitu pengumpulan data, pengamatan mendalam terhadap objek penciptaan, pengkajian sumber inspirasi, pembuatan desain motif, dan perwujudan menjadi batik. Dari penciptaan seni ini berhasil dikreasikan 6 (enam motif batik yaitu: (1 Motif Uwoh Kopi; (2 Motif Godong Kopi;  (3 Motif Ceplok Kakao; (4 Motif Kakao Raja; (5 Motif Kakao Biru; dan (6 Motif Wiji Mukti. Berdasarkan hasil penilaian “Selera Estetika” diketahui bahwa motif yang paling banyak disukai adalah Motif Uwoh Kopi dan Motif Kakao Raja. Kata kunci: Motif Woh Kopi, Motif Godong Kopi, Motif Ceplok Kakao, Motif Kakao Raja, Motif Kakao Biru, Motif Wiji Mukti ABSTRACTBatik Jember is synonymous with tobacco leaf motif. Tobacco leaf shape is quite weak in the visual appearance characterized as that motif emerges like a picture of leaves in general. Therefore, it is necessary to create a distinctive design motif extracted from other natural resources of Jember that have specific shapes and characteristics that can be obtained as the stronger motif identity. The typical natural resources from Jember are coffee and cocoa. The purpose of the creation of this art is to produce the unique, creative and innovative batik and have specific characteristics of Jember. The method used are data collection, observation of the object, reviewing inspiration sources

  13. Statistical tests to compare motif count exceptionalities

    Directory of Open Access Journals (Sweden)

    Vandewalle Vincent

    2007-03-01

    Full Text Available Abstract Background Finding over- or under-represented motifs in biological sequences is now a common task in genomics. Thanks to p-value calculation for motif counts, exceptional motifs are identified and represent candidate functional motifs. The present work addresses the related question of comparing the exceptionality of one motif in two different sequences. Just comparing the motif count p-values in each sequence is indeed not sufficient to decide if this motif is significantly more exceptional in one sequence compared to the other one. A statistical test is required. Results We develop and analyze two statistical tests, an exact binomial one and an asymptotic likelihood ratio test, to decide whether the exceptionality of a given motif is equivalent or significantly different in two sequences of interest. For that purpose, motif occurrences are modeled by Poisson processes, with a special care for overlapping motifs. Both tests can take the sequence compositions into account. As an illustration, we compare the octamer exceptionalities in the Escherichia coli K-12 backbone versus variable strain-specific loops. Conclusion The exact binomial test is particularly adapted for small counts. For large counts, we advise to use the likelihood ratio test which is asymptotic but strongly correlated with the exact binomial test and very simple to use.

  14. An Algorithm for Motif Discovery with Iteration on Lengths of Motifs.

    Science.gov (United States)

    Fan, Yetian; Wu, Wei; Yang, Jie; Yang, Wenyu; Liu, Rongrong

    2015-01-01

    Analysis of DNA sequence motifs is becoming increasingly important in the study of gene regulation, and the identification of motif in DNA sequences is a complex problem in computational biology. Motif discovery has attracted the attention of more and more researchers, and varieties of algorithms have been proposed. Most existing motif discovery algorithms fix the motif's length as one of the input parameters. In this paper, a novel method is proposed to identify the optimal length of the motif and the optimal motif with that length, through an iteration process on increasing length numbers. For each fixed length, a modified genetic algorithm (GA) is used for finding the optimal motif with that length. Three operators are used in the modified GA: Mutation that is similar to the one used in usual GA but is modified to avoid local optimum in our case, and Addition and Deletion that are proposed by us for the problem. A criterion is given for singling out the optimal length in the increasing motif's lengths. We call this method AMDILM (an algorithm for motif discovery with iteration on lengths of motifs). The experiments on simulated data and real biological data show that AMDILM can accurately identify the optimal motif length. Meanwhile, the optimal motifs discovered by AMDILM are consistent with the real ones and are similar with the motifs obtained by the three well-known methods: Gibbs Sampler, MEME and Weeder.

  15. rMotifGen: random motif generator for DNA and protein sequences

    Directory of Open Access Journals (Sweden)

    Hardin C Timothy

    2007-08-01

    Full Text Available Abstract Background Detection of short, subtle conserved motif regions within a set of related DNA or amino acid sequences can lead to discoveries about important regulatory domains such as transcription factor and DNA binding sites as well as conserved protein domains. In order to help assess motif detection algorithms on motifs with varying properties and levels of conservation, we have developed a computational tool, rMotifGen, with the sole purpose of generating a number of random DNA or protein sequences containing short sequence motifs. Each motif consensus can be user-defined, randomly generated, or created from a position-specific scoring matrix (PSSM. Insertions and mutations within these motifs are created according to user-defined parameters and substitution matrices. The resulting sequences can be helpful in mutational simulations and in testing the limits of motif detection algorithms. Results Two implementations of rMotifGen have been created, one providing a graphical user interface (GUI for random motif construction, and the other serving as a command line interface. The second implementation has the added advantages of platform independence and being able to be called in a batch mode. rMotifGen was used to construct sample sets of sequences containing DNA motifs and amino acid motifs that were then tested against the Gibbs sampler and MEME packages. Conclusion rMotifGen provides an efficient and convenient method for creating random DNA or amino acid sequences with a variable number of motifs, where the instance of each motif can be incorporated using a position-specific scoring matrix (PSSM or by creating an instance mutated from its corresponding consensus using an evolutionary model based on substitution matrices. rMotifGen is freely available at: http://bioinformatics.louisville.edu/brg/rMotifGen/.

  16. Motif Tool Manager: a web-based framework for motif discovery.

    Science.gov (United States)

    Phan, Vinhthuy; Furlotte, Nicholas A

    2008-12-15

    Motif Tool Manager is a web-based framework for comparing and combining different approaches to discover novel DNA motifs. It comes with a set of five well-known approaches to motif discovery. It provides an easy mechanism for adding new motif finding tools to the framework through a web-interface and a minimal setup of the tools on the server. Users can execute the tools through the web-based framework and compare results from such executions. The framework provides a basic mechanism for identifying the most similar motif candidates found by a majority of themotif finding tools. http://cetus.cs.memphis.edu/motif

  17. Fitness for synchronization of network motifs

    DEFF Research Database (Denmark)

    Vega, Y.M.; Vázquez-Prada, M.; Pacheco, A.F.

    2004-01-01

    We study the synchronization of Kuramoto's oscillators in small parts of networks known as motifs. We first report on the system dynamics for the case of a scale-free network and show the existence of a non-trivial critical point. We compute the probability that network motifs synchronize, and fi...... that the fitness for synchronization correlates well with motifs interconnectedness and structural complexity. Possible implications for present debates about network evolution in biological and other systems are discussed....

  18. Motif discovery using optimized suffix tries

    OpenAIRE

    Prado Martínez, Sergio

    2012-01-01

    Motif discovery is a challenging problem from a computational point of view [5] [6]. Binding sites are better conserved in DNA because they have a biological function and are therefore under selective pressure. Motif discovery algorithms can help us detect them. To tackle our problem we design and implement an index structure and a motif discovery algorithm. In this thesis we will investigate memory and performance optimizations. En el present article es presenta una implementació d'un ...

  19. MSDmotif: exploring protein sites and motifs

    Directory of Open Access Journals (Sweden)

    Henrick Kim

    2008-07-01

    Full Text Available Abstract Background Protein structures have conserved features – motifs, which have a sufficient influence on the protein function. These motifs can be found in sequence as well as in 3D space. Understanding of these fragments is essential for 3D structure prediction, modelling and drug-design. The Protein Data Bank (PDB is the source of this information however present search tools have limited 3D options to integrate protein sequence with its 3D structure. Results We describe here a web application for querying the PDB for ligands, binding sites, small 3D structural and sequence motifs and the underlying database. Novel algorithms for chemical fragments, 3D motifs, ϕ/ψ sequences, super-secondary structure motifs and for small 3D structural motif associations searches are incorporated. The interface provides functionality for visualization, search criteria creation, sequence and 3D multiple alignment options. MSDmotif is an integrated system where a results page is also a search form. A set of motif statistics is available for analysis. This set includes molecule and motif binding statistics, distribution of motif sequences, occurrence of an amino-acid within a motif, correlation of amino-acids side-chain charges within a motif and Ramachandran plots for each residue. The binding statistics are presented in association with properties that include a ligand fragment library. Access is also provided through the distributed Annotation System (DAS protocol. An additional entry point facilitates XML requests with XML responses. Conclusion MSDmotif is unique by combining chemical, sequence and 3D data in a single search engine with a range of search and visualisation options. It provides multiple views of data found in the PDB archive for exploring protein structures.

  20. Assessment of composite motif discovery methods

    Directory of Open Access Journals (Sweden)

    Johansen Jostein

    2008-02-01

    Full Text Available Abstract Background Computational discovery of regulatory elements is an important area of bioinformatics research and more than a hundred motif discovery methods have been published. Traditionally, most of these methods have addressed the problem of single motif discovery – discovering binding motifs for individual transcription factors. In higher organisms, however, transcription factors usually act in combination with nearby bound factors to induce specific regulatory behaviours. Hence, recent focus has shifted from single motifs to the discovery of sets of motifs bound by multiple cooperating transcription factors, so called composite motifs or cis-regulatory modules. Given the large number and diversity of methods available, independent assessment of methods becomes important. Although there have been several benchmark studies of single motif discovery, no similar studies have previously been conducted concerning composite motif discovery. Results We have developed a benchmarking framework for composite motif discovery and used it to evaluate the performance of eight published module discovery tools. Benchmark datasets were constructed based on real genomic sequences containing experimentally verified regulatory modules, and the module discovery programs were asked to predict both the locations of these modules and to specify the single motifs involved. To aid the programs in their search, we provided position weight matrices corresponding to the binding motifs of the transcription factors involved. In addition, selections of decoy matrices were mixed with the genuine matrices on one dataset to test the response of programs to varying levels of noise. Conclusion Although some of the methods tested tended to score somewhat better than others overall, there were still large variations between individual datasets and no single method performed consistently better than the rest in all situations. The variation in performance on individual

  1. PMS: a panoptic motif search tool.

    Directory of Open Access Journals (Sweden)

    Hieu Dinh

    Full Text Available Identification of DNA/Protein motifs is a crucial problem for biologists. Computational techniques could be of great help in this identification. In this direction, many computational models for motifs have been proposed in the literature.One such important model is the (l,d motif model. In this paper we describe a motif search web tool that predominantly employs this motif model. This web tool exploits the state-of-the art algorithms for solving the (l,d motif search problem.The online tool has been helping scientists identify many unknown motifs. Many of our predictions have been successfully verified as well. We hope that this paper will expose this crucial tool to many more scientists.Project name: PMS--Panoptic Motif Search Tool. Project home page: http://pms.engr.uconn.edu or http://motifsearch.com. Licence: PMS tools will be readily available to any scientist wishing to use it for non-commercial purposes, without restrictions. The online tool is freely available without login.

  2. MotifNet: a web-server for network motif analysis.

    Science.gov (United States)

    Smoly, Ilan Y; Lerman, Eugene; Ziv-Ukelson, Michal; Yeger-Lotem, Esti

    2017-06-15

    Network motifs are small topological patterns that recur in a network significantly more often than expected by chance. Their identification emerged as a powerful approach for uncovering the design principles underlying complex networks. However, available tools for network motif analysis typically require download and execution of computationally intensive software on a local computer. We present MotifNet, the first open-access web-server for network motif analysis. MotifNet allows researchers to analyze integrated networks, where nodes and edges may be labeled, and to search for motifs of up to eight nodes. The output motifs are presented graphically and the user can interactively filter them by their significance, number of instances, node and edge labels, and node identities, and view their instances. MotifNet also allows the user to distinguish between motifs that are centered on specific nodes and motifs that recur in distinct parts of the network. MotifNet is freely available at http://netbio.bgu.ac.il/motifnet . The website was implemented using ReactJs and supports all major browsers. The server interface was implemented in Python with data stored on a MySQL database. estiyl@bgu.ac.il or michaluz@cs.bgu.ac.il. Supplementary data are available at Bioinformatics online.

  3. CompleteMOTIFs: DNA motif discovery platform for transcription factor binding experiments.

    Science.gov (United States)

    Kuttippurathu, Lakshmi; Hsing, Michael; Liu, Yongchao; Schmidt, Bertil; Maskell, Douglas L; Lee, Kyungjoon; He, Aibin; Pu, William T; Kong, Sek Won

    2011-03-01

    CompleteMOTIFs (cMOTIFs) is an integrated web tool developed to facilitate systematic discovery of overrepresented transcription factor binding motifs from high-throughput chromatin immunoprecipitation experiments. Comprehensive annotations and Boolean logic operations on multiple peak locations enable users to focus on genomic regions of interest for de novo motif discovery using tools such as MEME, Weeder and ChIPMunk. The pipeline incorporates a scanning tool for known motifs from TRANSFAC and JASPAR databases, and performs an enrichment test using local or precalculated background models that significantly improve the motif scanning result. Furthermore, using the cMOTIFs pipeline, we demonstrated that multiple transcription factors could cooperatively bind to the upstream of important stem cell differentiation regulators. http://cmotifs.tchlab.org.

  4. Improved benchmarks for computational motif discovery

    Directory of Open Access Journals (Sweden)

    Walseng Vegard

    2007-06-01

    Full Text Available Abstract Background An important step in annotation of sequenced genomes is the identification of transcription factor binding sites. More than a hundred different computational methods have been proposed, and it is difficult to make an informed choice. Therefore, robust assessment of motif discovery methods becomes important, both for validation of existing tools and for identification of promising directions for future research. Results We use a machine learning perspective to analyze collections of transcription factors with known binding sites. Algorithms are presented for finding position weight matrices (PWMs, IUPAC-type motifs and mismatch motifs with optimal discrimination of binding sites from remaining sequence. We show that for many data sets in a recently proposed benchmark suite for motif discovery, none of the common motif models can accurately discriminate the binding sites from remaining sequence. This may obscure the distinction between the potential performance of the motif discovery tool itself versus the intrinsic complexity of the problem we are trying to solve. Synthetic data sets may avoid this problem, but we show on some previously proposed benchmarks that there may be a strong bias towards a presupposed motif model. We also propose a new approach to benchmark data set construction. This approach is based on collections of binding site fragments that are ranked according to the optimal level of discrimination achieved with our algorithms. This allows us to select subsets with specific properties. We present one benchmark suite with data sets that allow good discrimination between positive and negative instances with the common motif models. These data sets are suitable for evaluating algorithms for motif discovery that rely on these models. We present another benchmark suite where PWM, IUPAC and mismatch motif models are not able to discriminate reliably between positive and negative instances. This suite could be used

  5. Combining phylogenetic footprinting with motif models incorporating intra-motif dependencies.

    Science.gov (United States)

    Nettling, Martin; Treutler, Hendrik; Cerquides, Jesus; Grosse, Ivo

    2017-03-01

    Transcriptional gene regulation is a fundamental process in nature, and the experimental and computational investigation of DNA binding motifs and their binding sites is a prerequisite for elucidating this process. Approaches for de-novo motif discovery can be subdivided in phylogenetic footprinting that takes into account phylogenetic dependencies in aligned sequences of more than one species and non-phylogenetic approaches based on sequences from only one species that typically take into account intra-motif dependencies. It has been shown that modeling (i) phylogenetic dependencies as well as (ii) intra-motif dependencies separately improves de-novo motif discovery, but there is no approach capable of modeling both (i) and (ii) simultaneously. Here, we present an approach for de-novo motif discovery that combines phylogenetic footprinting with motif models capable of taking into account intra-motif dependencies. We study the degree of intra-motif dependencies inferred by this approach from ChIP-seq data of 35 transcription factors. We find that significant intra-motif dependencies of orders 1 and 2 are present in all 35 datasets and that intra-motif dependencies of order 2 are typically stronger than those of order 1. We also find that the presented approach improves the classification performance of phylogenetic footprinting in all 35 datasets and that incorporating intra-motif dependencies of order 2 yields a higher classification performance than incorporating such dependencies of only order 1. Combining phylogenetic footprinting with motif models incorporating intra-motif dependencies leads to an improved performance in the classification of transcription factor binding sites. This may advance our understanding of transcriptional gene regulation and its evolution.

  6. MotifLab: a tools and data integration workbench for motif discovery and regulatory sequence analysis.

    Science.gov (United States)

    Klepper, Kjetil; Drabløs, Finn

    2013-01-16

    Traditional methods for computational motif discovery often suffer from poor performance. In particular, methods that search for sequence matches to known binding motifs tend to predict many non-functional binding sites because they fail to take into consideration the biological state of the cell. In recent years, genome-wide studies have generated a lot of data that has the potential to improve our ability to identify functional motifs and binding sites, such as information about chromatin accessibility and epigenetic states in different cell types. However, it is not always trivial to make use of this data in combination with existing motif discovery tools, especially for researchers who are not skilled in bioinformatics programming. Here we present MotifLab, a general workbench for analysing regulatory sequence regions and discovering transcription factor binding sites and cis-regulatory modules. MotifLab supports comprehensive motif discovery and analysis by allowing users to integrate several popular motif discovery tools as well as different kinds of additional information, including phylogenetic conservation, epigenetic marks, DNase hypersensitive sites, ChIP-Seq data, positional binding preferences of transcription factors, transcription factor interactions and gene expression. MotifLab offers several data-processing operations that can be used to create, manipulate and analyse data objects, and complete analysis workflows can be constructed and automatically executed within MotifLab, including graphical presentation of the results. We have developed MotifLab as a flexible workbench for motif analysis in a genomic context. The flexibility and effectiveness of this workbench has been demonstrated on selected test cases, in particular two previously published benchmark data sets for single motifs and modules, and a realistic example of genes responding to treatment with forskolin. MotifLab is freely available at http://www.motiflab.org.

  7. A frequent, GxxxG-mediated, transmembrane association motif is optimized for the formation of interhelical Cα–H hydrogen bonds

    OpenAIRE

    Mueller, Benjamin K.; Subramaniam, Sabareesh; Senes, Alessandro

    2014-01-01

    The transmembrane helices of single-span membrane proteins are commonly engaged in oligomeric interactions that are essential for structure and function. These interactions often occur in the form of recurrent structural motifs. Here we present an analysis of one of the most important motifs (GASright), showing that its geometry is optimized to form carbon hydrogen bonds at the helix−helix interface. The analysis reveals the structural basis for its characteristic GxxxG sequence signature. We...

  8. A Conserved GPG-Motif in the HIV-1 Nef Core Is Required for Principal Nef-Activities.

    Directory of Open Access Journals (Sweden)

    Marta Martínez-Bonet

    Full Text Available To find out new determinants required for Nef activity we performed a functional alanine scanning analysis along a discrete but highly conserved region at the core of HIV-1 Nef. We identified the GPG-motif, located at the 121-137 region of HIV-1 NL4.3 Nef, as a novel protein signature strictly required for the p56Lck dependent Nef-induced CD4-downregulation in T-cells. Since the Nef-GPG motif was dispensable for CD4-downregulation in HeLa-CD4 cells, Nef/AP-1 interaction and Nef-dependent effects on Tf-R trafficking, the observed effects on CD4 downregulation cannot be attributed to structure constraints or to alterations on general protein trafficking. Besides, we found that the GPG-motif was also required for Nef-dependent inhibition of ring actin re-organization upon TCR triggering and MHCI downregulation, suggesting that the GPG-motif could actively cooperate with the Nef PxxP motif for these HIV-1 Nef-related effects. Finally, we observed that the Nef-GPG motif was required for optimal infectivity of those viruses produced in T-cells. According to these findings, we propose the conserved GPG-motif in HIV-1 Nef as functional region required for HIV-1 infectivity and therefore with a potential interest for the interference of Nef activity during HIV-1 infection.

  9. Hunting Motifs in Situla Art

    Directory of Open Access Journals (Sweden)

    Andrej Preložnik

    2013-07-01

    Full Text Available Situla art developed as an echo of the toreutic style which had spread from the Near East through the Phoenicians, Greeks and Etruscans as far as the Veneti, Raeti, Histri, and their eastern neighbours in the region of Dolenjska (Lower Carniola. An Early Iron Age phenomenon (c. 600—300 BC, it rep- resents the major and most arresting form of the contemporary visual arts in an area stretching from the foot of the Apennines in the south to the Drava and Sava rivers in the east. Indeed, individual pieces have found their way across the Alpine passes and all the way north to the Danube. In the world and art of the situlae, a prominent role is accorded to ani- mals. They are displayed in numerous representations of human activities on artefacts crafted in the classic situla style – that is, between the late 6th  and early 5th centuries BC – as passive participants (e.g. in pageants or in harness or as an active element of the situla narrative. The most typical example of the latter is the hunting scene. Today we know at least four objects decorat- ed exclusively with hunting themes, and a number of situlae and other larger vessels where hunting scenes are embedded in composite narratives. All this suggests a popularity unparallelled by any other genre. Clearly recognisable are various hunting techniques and weapons, each associated with a particu- lar type of game (Fig. 1. The chase of a stag with javelin, horse and hound is depicted on the long- familiar and repeatedly published fibula of Zagorje (Fig. 2. It displays a hound mauling the stag’s back and a hunter on horseback pursuing a hind, her neck already pierced by the javelin. To judge by the (so far unnoticed shaft end un- der the stag’s muzzle, the hunter would have been brandishing a second jave- lin as well, like the warrior of the Vače fibula or the rider of the Nesactium situla, presumably himself a hunter. Many parallels to his motif are known from Greece, Etruria, and

  10. Automated classification of RNA 3D motifs and the RNA 3D Motif Atlas

    Science.gov (United States)

    Petrov, Anton I.; Zirbel, Craig L.; Leontis, Neocles B.

    2013-01-01

    The analysis of atomic-resolution RNA three-dimensional (3D) structures reveals that many internal and hairpin loops are modular, recurrent, and structured by conserved non-Watson–Crick base pairs. Structurally similar loops define RNA 3D motifs that are conserved in homologous RNA molecules, but can also occur at nonhomologous sites in diverse RNAs, and which often vary in sequence. To further our understanding of RNA motif structure and sequence variability and to provide a useful resource for structure modeling and prediction, we present a new method for automated classification of internal and hairpin loop RNA 3D motifs and a new online database called the RNA 3D Motif Atlas. To classify the motif instances, a representative set of internal and hairpin loops is automatically extracted from a nonredundant list of RNA-containing PDB files. Their structures are compared geometrically, all-against-all, using the FR3D program suite. The loops are clustered into motif groups, taking into account geometric similarity and structural annotations and making allowance for a variable number of bulged bases. The automated procedure that we have implemented identifies all hairpin and internal loop motifs previously described in the literature. All motif instances and motif groups are assigned unique and stable identifiers and are made available in the RNA 3D Motif Atlas (http://rna.bgsu.edu/motifs), which is automatically updated every four weeks. The RNA 3D Motif Atlas provides an interactive user interface for exploring motif diversity and tools for programmatic data access. PMID:23970545

  11. Radar Signature Calculation Facility

    Data.gov (United States)

    Federal Laboratory Consortium — FUNCTION: The calculation, analysis, and visualization of the spatially extended radar signatures of complex objects such as ships in a sea multipath environment and...

  12. Blind Collective Signature Protocol

    Directory of Open Access Journals (Sweden)

    Nikolay A. Moldovyan

    2011-06-01

    Full Text Available Using the digital signature (DS scheme specified by Belarusian DS standard there are designed the collective and blind collective DS protocols. Signature formation is performed simultaneously by all of the assigned signers, therefore the proposed protocols can be used also as protocols for simultaneous signing a contract. The proposed blind collective DS protocol represents a particular implementation of the blind multisignature schemes that is a novel type of the signature schemes. The proposed protocols are the first implementations of the multisignature schemes based on Belarusian signature standard.

  13. Unconditionally Secure Quantum Signatures

    Directory of Open Access Journals (Sweden)

    Ryan Amiri

    2015-08-01

    Full Text Available Signature schemes, proposed in 1976 by Diffie and Hellman, have become ubiquitous across modern communications. They allow for the exchange of messages from one sender to multiple recipients, with the guarantees that messages cannot be forged or tampered with and that messages also can be forwarded from one recipient to another without compromising their validity. Signatures are different from, but no less important than encryption, which ensures the privacy of a message. Commonly used signature protocols—signatures based on the Rivest–Adleman–Shamir (RSA algorithm, the digital signature algorithm (DSA, and the elliptic curve digital signature algorithm (ECDSA—are only computationally secure, similar to public key encryption methods. In fact, since these rely on the difficulty of finding discrete logarithms or factoring large primes, it is known that they will become completely insecure with the emergence of quantum computers. We may therefore see a shift towards signature protocols that will remain secure even in a post-quantum world. Ideally, such schemes would provide unconditional or information-theoretic security. In this paper, we aim to provide an accessible and comprehensive review of existing unconditionally securesecure signature schemes for signing classical messages, with a focus on unconditionally secure quantum signature schemes.

  14. Bayesian centroid estimation for motif discovery.

    Science.gov (United States)

    Carvalho, Luis

    2013-01-01

    Biological sequences may contain patterns that signal important biomolecular functions; a classical example is regulation of gene expression by transcription factors that bind to specific patterns in genomic promoter regions. In motif discovery we are given a set of sequences that share a common motif and aim to identify not only the motif composition, but also the binding sites in each sequence of the set. We propose a new centroid estimator that arises from a refined and meaningful loss function for binding site inference. We discuss the main advantages of centroid estimation for motif discovery, including computational convenience, and how its principled derivation offers further insights about the posterior distribution of binding site configurations. We also illustrate, using simulated and real datasets, that the centroid estimator can differ from the traditional maximum a posteriori or maximum likelihood estimators.

  15. POWRS: position-sensitive motif discovery

    National Research Council Canada - National Science Library

    Davis, Ian W; Benninger, Christopher; Benfey, Philip N; Elich, Tedd

    2012-01-01

    .... Here we present a new algorithm "POWRS" (POsition-sensitive WoRd Set) for identifying regulatory sequence motifs, specifically developed to address two common shortcomings of existing algorithms...

  16. MotifMiner: A Table Driven Greedy Algorithm for DNA Motif Mining

    Science.gov (United States)

    Seeja, K. R.; Alam, M. A.; Jain, S. K.

    DNA motif discovery is a much explored problem in functional genomics. This paper describes a table driven greedy algorithm for discovering regulatory motifs in the promoter sequences of co-expressed genes. The proposed algorithm searches both DNA strands for the common patterns or motifs. The inputs to the algorithm are set of promoter sequences, the motif length and minimum Information Content. The algorithm generates subsequences of given length from the shortest input promoter sequence. It stores these subsequences and their reverse complements in a table. Then it searches the remaining sequences for good matches of these subsequences. The Information Content score is used to measure the goodness of the motifs. The algorithm has been tested with synthetic data and real data. The results are found promising. The algorithm could discover meaningful motifs from the muscle specific regulatory sequences.

  17. MotifHyades: expectation maximization for de novo DNA motif pair discovery on paired sequences.

    Science.gov (United States)

    Wong, Ka-Chun

    2017-10-01

    In higher eukaryotes, protein-DNA binding interactions are the central activities in gene regulation. In particular, DNA motifs such as transcription factor binding sites are the key components in gene transcription. Harnessing the recently available chromatin interaction data, computational methods are desired for identifying the coupling DNA motif pairs enriched on long-range chromatin-interacting sequence pairs (e.g. promoter-enhancer pairs) systematically. To fill the void, a novel probabilistic model (namely, MotifHyades) is proposed and developed for de novo DNA motif pair discovery on paired sequences. In particular, two expectation maximization algorithms are derived for efficient model training with linear computational complexity. Under diverse scenarios, MotifHyades is demonstrated faster and more accurate than the existing ad hoc computational pipeline. In addition, MotifHyades is applied to discover thousands of DNA motif pairs with higher gold standard motif matching ratio, higher DNase accessibility and higher evolutionary conservation than the previous ones in the human K562 cell line. Lastly, it has been run on five other human cell lines (i.e. GM12878, HeLa-S3, HUVEC, IMR90, and NHEK), revealing another thousands of novel DNA motif pairs which are characterized across a broad spectrum of genomic features on long-range promoter-enhancer pairs. The matrix-algebra-optimized versions of MotifHyades and the discovered DNA motif pairs can be found in http://bioinfo.cs.cityu.edu.hk/MotifHyades. kc.w@cityu.edu.hk. Supplementary data are available at Bioinformatics online.

  18. Digital Signature Management.

    Science.gov (United States)

    Hassler, Vesna; Biely, Helmut

    1999-01-01

    Describes the Digital Signature Project that was developed in Austria to establish an infrastructure for applying smart card-based digital signatures in banking and electronic-commerce applications. Discusses the need to conform to international standards, an international certification infrastructure, and security features for a public directory…

  19. Modeling gene regulatory network motifs using Statecharts.

    Science.gov (United States)

    Fioravanti, Fabio; Helmer-Citterich, Manuela; Nardelli, Enrico

    2012-03-28

    Gene regulatory networks are widely used by biologists to describe the interactions among genes, proteins and other components at the intra-cellular level. Recently, a great effort has been devoted to give gene regulatory networks a formal semantics based on existing computational frameworks.For this purpose, we consider Statecharts, which are a modular, hierarchical and executable formal model widely used to represent software systems. We use Statecharts for modeling small and recurring patterns of interactions in gene regulatory networks, called motifs. We present an improved method for modeling gene regulatory network motifs using Statecharts and we describe the successful modeling of several motifs, including those which could not be modeled or whose models could not be distinguished using the method of a previous proposal.We model motifs in an easy and intuitive way by taking advantage of the visual features of Statecharts. Our modeling approach is able to simulate some interesting temporal properties of gene regulatory network motifs: the delay in the activation and the deactivation of the "output" gene in the coherent type-1 feedforward loop, the pulse in the incoherent type-1 feedforward loop, the bistability nature of double positive and double negative feedback loops, the oscillatory behavior of the negative feedback loop, and the "lock-in" effect of positive autoregulation. We present a Statecharts-based approach for the modeling of gene regulatory network motifs in biological systems. The basic motifs used to build more complex networks (that is, simple regulation, reciprocal regulation, feedback loop, feedforward loop, and autoregulation) can be faithfully described and their temporal dynamics can be analyzed.

  20. UV Signature Mutations †

    Science.gov (United States)

    2014-01-01

    Sequencing complete tumor genomes and exomes has sparked the cancer field's interest in mutation signatures for identifying the tumor's carcinogen. This review and meta-analysis discusses signatures and their proper use. We first distinguish between a mutagen's canonical mutations – deviations from a random distribution of base changes to create a pattern typical of that mutagen – and the subset of signature mutations, which are unique to that mutagen and permit inference backward from mutations to mutagen. To verify UV signature mutations, we assembled literature datasets on cells exposed to UVC, UVB, UVA, or solar simulator light (SSL) and tested canonical UV mutation features as criteria for clustering datasets. A confirmed UV signature was: ≥60% of mutations are C→T at a dipyrimidine site, with ≥5% CC→TT. Other canonical features such as a bias for mutations on the non-transcribed strand or at the 3' pyrimidine had limited application. The most robust classifier combined these features with criteria for the rarity of non-UV canonical mutations. In addition, several signatures proposed for specific UV wavelengths were limited to specific genes or species; non-signature mutations induced by UV may cause melanoma BRAF mutations; and the mutagen for sunlight-related skin neoplasms may vary between continents. PMID:25354245

  1. Analisis Unsur Matematika pada Motif Sulam Usus

    Directory of Open Access Journals (Sweden)

    Fredi Ganda Putra

    2017-12-01

    Full Text Available Based on interviews with researchers sources said that the beginning of the intestine embroidery is an art of genuine crafts. Called the intestine embroidery because this technique is a technique of combining a strand of cloth resembling the intestine formed according to the pattern by means of embroidered using a thread. Intestinal embroidery techniques were originally used to create a cover of the women's customary wardrobe of Lampung or often referred to as bebe. But not many people in Lampung, especially people who live in Lampung are still many who do not know and recognize the intestine embroidery because most only know tapis only characteristic of Lampung, besides that there are other cultural results that is embroidered intestine. There are still many who do not know that the intestine motif there is a knowledge of mathematics. The researcher's problem formulation is whether there are mathematical elements contained in the intestine embroidery motif based on the concept of geometry. The purpose of this study is to determine whether there are elements of mathematics contained in the intestine motif based on the concept of geometry. Subjects in this study consisted of 4 people obtained by purposive sampling technique. From the results of data analysis conducted by using descriptive analysis and discussion as follows: (1 Intestinal embroidery motif contains the meaning of mathematics and culture or often called Etnomatematika. On the meaning of culture there is a link between the embroidery intestine with a culture that has been there before as the existence of cultural linkage between Hindu belief Buddhism and there are similarities of motifs and decorative patterns contained in the motif embroidery intestine with ornamental variety in Indonesia. (2 The relationship between the intestine with mathematical motifs there are elements of mathematics such as geometry elements in the form of geometry of dimension one and dimension two, and the

  2. SVM2Motif--Reconstructing Overlapping DNA Sequence Motifs by Mimicking an SVM Predictor.

    Directory of Open Access Journals (Sweden)

    Marina M-C Vidovic

    Full Text Available Identifying discriminative motifs underlying the functionality and evolution of organisms is a major challenge in computational biology. Machine learning approaches such as support vector machines (SVMs achieve state-of-the-art performances in genomic discrimination tasks, but--due to its black-box character--motifs underlying its decision function are largely unknown. As a remedy, positional oligomer importance matrices (POIMs allow us to visualize the significance of position-specific subsequences. Although being a major step towards the explanation of trained SVM models, they suffer from the fact that their size grows exponentially in the length of the motif, which renders their manual inspection feasible only for comparably small motif sizes, typically k ≤ 5. In this work, we extend the work on positional oligomer importance matrices, by presenting a new machine-learning methodology, entitled motifPOIM, to extract the truly relevant motifs--regardless of their length and complexity--underlying the predictions of a trained SVM model. Our framework thereby considers the motifs as free parameters in a probabilistic model, a task which can be phrased as a non-convex optimization problem. The exponential dependence of the POIM size on the oligomer length poses a major numerical challenge, which we address by an efficient optimization framework that allows us to find possibly overlapping motifs consisting of up to hundreds of nucleotides. We demonstrate the efficacy of our approach on a synthetic data set as well as a real-world human splice site data set.

  3. SVM2Motif--Reconstructing Overlapping DNA Sequence Motifs by Mimicking an SVM Predictor.

    Science.gov (United States)

    Vidovic, Marina M-C; Görnitz, Nico; Müller, Klaus-Robert; Rätsch, Gunnar; Kloft, Marius

    2015-01-01

    Identifying discriminative motifs underlying the functionality and evolution of organisms is a major challenge in computational biology. Machine learning approaches such as support vector machines (SVMs) achieve state-of-the-art performances in genomic discrimination tasks, but--due to its black-box character--motifs underlying its decision function are largely unknown. As a remedy, positional oligomer importance matrices (POIMs) allow us to visualize the significance of position-specific subsequences. Although being a major step towards the explanation of trained SVM models, they suffer from the fact that their size grows exponentially in the length of the motif, which renders their manual inspection feasible only for comparably small motif sizes, typically k ≤ 5. In this work, we extend the work on positional oligomer importance matrices, by presenting a new machine-learning methodology, entitled motifPOIM, to extract the truly relevant motifs--regardless of their length and complexity--underlying the predictions of a trained SVM model. Our framework thereby considers the motifs as free parameters in a probabilistic model, a task which can be phrased as a non-convex optimization problem. The exponential dependence of the POIM size on the oligomer length poses a major numerical challenge, which we address by an efficient optimization framework that allows us to find possibly overlapping motifs consisting of up to hundreds of nucleotides. We demonstrate the efficacy of our approach on a synthetic data set as well as a real-world human splice site data set.

  4. MOTIFATOR : detection and characterization of regulatory motifs using prokaryote transcriptome data

    NARCIS (Netherlands)

    Blom, Evert-Jan; Roerdink, Jos B.T.M.; Kuipers, Oscar P.; Hijum, Sacha A.F.T. van

    2009-01-01

    Unraveling regulatory mechanisms (e.g. identification of motifs in cis-regulatory regions) remains a major challenge in the analysis of transcriptome experiments. Existing applications identify putative motifs from gene lists obtained at rather arbitrary cutoff and require additional manual

  5. Sublinear Time Motif Discovery from Multiple Sequences

    Directory of Open Access Journals (Sweden)

    Yunhui Fu

    2013-10-01

    Full Text Available In this paper, a natural probabilistic model for motif discovery has been used to experimentally test the quality of motif discovery programs. In this model, there are k background sequences, and each character in a background sequence is a random character from an alphabet, Σ. A motif G = g1g2 ... gm is a string of m characters. In each background sequence is implanted a probabilistically-generated approximate copy of G. For a probabilistically-generated approximate copy b1b2 ... bm of G, every character, bi, is probabilistically generated, such that the probability for bi ≠ gi is at most α. We develop two new randomized algorithms and one new deterministic algorithm. They make advancements in the following aspects: (1 The algorithms are much faster than those before. Our algorithms can even run in sublinear time. (2 They can handle any motif pattern. (3 The restriction for the alphabet size is a lower bound of four. This gives them potential applications in practical problems, since gene sequences have an alphabet size of four. (4 All algorithms have rigorous proofs about their performances. The methods developed in this paper have been used in the software implementation. We observed some encouraging results that show improved performance for motif detection compared with other software.

  6. Functional characterization of variations on regulatory motifs.

    Directory of Open Access Journals (Sweden)

    Michal Lapidot

    2008-03-01

    Full Text Available Transcription factors (TFs regulate gene expression through specific interactions with short promoter elements. The same regulatory protein may recognize a variety of related sequences. Moreover, once they are detected it is hard to predict whether highly similar sequence motifs will be recognized by the same TF and regulate similar gene expression patterns, or serve as binding sites for distinct regulatory factors. We developed computational measures to assess the functional implications of variations on regulatory motifs and to compare the functions of related sites. We have developed computational means for estimating the functional outcome of substituting a single position within a binding site and applied them to a collection of putative regulatory motifs. We predict the effects of nucleotide variations within motifs on gene expression patterns. In cases where such predictions could be compared to suitable published experimental evidence, we found very good agreement. We further accumulated statistics from multiple substitutions across various binding sites in an attempt to deduce general properties that characterize nucleotide substitutions that are more likely to alter expression. We found that substitutions involving Adenine are more likely to retain the expression pattern and that substitutions involving Guanine are more likely to alter expression compared to the rest of the substitutions. Our results should facilitate the prediction of the expression outcomes of binding site variations. One typical important implication is expected to be the ability to predict the phenotypic effect of variation in regulatory motifs in promoters.

  7. Defect Motifs for Constant Mean Curvature Surfaces

    Science.gov (United States)

    Kusumaatmaja, Halim; Wales, David J.

    2013-04-01

    The energy landscapes of electrostatically charged particles embedded on constant mean curvature surfaces are analyzed for a wide range of system size, curvature, and interaction potentials. The surfaces are taken to be rigid, and the basin-hopping method is used to locate the putative global minimum structures. The defect motifs favored by potential energy agree with experimental observations for colloidal systems: extended defects (scars and pleats) for weakly positive and negative Gaussian curvatures, and isolated defects for strongly negative Gaussian curvatures. Near the phase boundary between these regimes, the two motifs are in strong competition, as evidenced from the appearance of distinct funnels in the potential energy landscape. We also report a novel defect motif consisting of pentagon pairs.

  8. Analysis of computational approaches for motif discovery

    Directory of Open Access Journals (Sweden)

    Tompa Martin

    2006-05-01

    Full Text Available Abstract Recently, we performed an assessment of 13 popular computational tools for discovery of transcription factor binding sites (M. Tompa, N. Li, et al., "Assessing Computational Tools for the Discovery of Transcription Factor Binding Sites", Nature Biotechnology, Jan. 2005. This paper contains follow-up analysis of the assessment results, and raises and discusses some important issues concerning the state of the art in motif discovery methods: 1. We categorize the objective functions used by existing tools, and design experiments to evaluate whether any of these objective functions is the right one to optimize. 2. We examine various features of the data sets that were used in the assessment, such as sequence length and motif degeneracy, and identify which features make data sets hard for current motif discovery tools. 3. We identify an important feature that has not yet been used by existing tools and propose a new objective function that incorporates this feature.

  9. Advanced Missile Signature Center

    Data.gov (United States)

    Federal Laboratory Consortium — The Advanced Missile Signature Center (AMSC) is a national facility supporting the Missile Defense Agency (MDA) and other DoD programs and customers with analysis,...

  10. THE ELECTRONIC SIGNATURE

    Directory of Open Access Journals (Sweden)

    Voiculescu Madalina Irena

    2009-05-01

    Full Text Available Article refers to significance and the digital signature in electronic commerce. Internet and electronic commerce open up many new opportunities for the consumer, yet, the security (or perceived lack of security of exchanging personal and financial data

  11. Digital signature feasibility study

    Science.gov (United States)

    2008-06-01

    The purpose of this study was to assess the advantages and disadvantages of using digital signatures to assist the Arizona Department of Transportation in conducting business. The Department is evaluating the potential of performing more electronic t...

  12. Are there molecular signatures?

    Energy Technology Data Exchange (ETDEWEB)

    Bennett, W.P.

    1995-10-01

    This report describes molecular signatures and mutational spectrum analysis. The mutation spectrum is defined as the type and location of DNA base change. There are currently about five well documented cases. Mutations and radon-associated tumors are discussed.

  13. Direct AUC optimization of regulatory motifs.

    Science.gov (United States)

    Zhu, Lin; Zhang, Hong-Bo; Huang, De-Shuang

    2017-07-15

    The discovery of transcription factor binding site (TFBS) motifs is essential for untangling the complex mechanism of genetic variation under different developmental and environmental conditions. Among the huge amount of computational approaches for de novo identification of TFBS motifs, discriminative motif learning (DML) methods have been proven to be promising for harnessing the discovery power of accumulated huge amount of high-throughput binding data. However, they have to sacrifice accuracy for speed and could fail to fully utilize the information of the input sequences. We propose a novel algorithm called CDAUC for optimizing DML-learned motifs based on the area under the receiver-operating characteristic curve (AUC) criterion, which has been widely used in the literature to evaluate the significance of extracted motifs. We show that when the considered AUC loss function is optimized in a coordinate-wise manner, the cost function of each resultant sub-problem is a piece-wise constant function, whose optimal value can be found exactly and efficiently. Further, a key step of each iteration of CDAUC can be efficiently solved as a computational geometry problem. Experimental results on real world high-throughput datasets illustrate that CDAUC outperforms competing methods for refining DML motifs, while being one order of magnitude faster. Meanwhile, preliminary results also show that CDAUC may also be useful for improving the interpretability of convolutional kernels generated by the emerging deep learning approaches for predicting TF sequences specificities. CDAUC is available at: https://drive.google.com/drive/folders/0BxOW5MtIZbJjNFpCeHlBVWJHeW8 . dshuang@tongji.edu.cn. Supplementary data are available at Bioinformatics online.

  14. cWords - systematic microRNA regulatory motif discovery from mRNA expression data

    DEFF Research Database (Denmark)

    Rasmussen, Simon Horskjær; Jacobsen, Anders; Krogh, Anders

    2013-01-01

    -transcriptional regulation by small RNAs is mediated through partial complementary binding to messenger RNAs leaving nucleotide signatures or motifs throughout the entire transcriptome. Computational methods for discovery and analysis of sequence motifs in high-throughput mRNA expression profiling experiments are becoming......BACKGROUND:Post-transcriptional regulation of gene expression by small RNAs and RNA binding proteins is of fundamental importance in development of complex organisms, and dysregulation of regulatory RNAs can influence onset, progression and potentially be target for treatment of many diseases. Post...... clustering and visualization that accompany the cWords analysis for more intuitive and effective data interpretation. To demonstrate the versatility of cWords we show that it can also be used for identification of potential siRNA off-target binding. Moreover, cWords analysis of an experiment profiling mRNAs...

  15. Technology of Electronic Signatur

    Directory of Open Access Journals (Sweden)

    Jaroslav Sadovsky

    2004-01-01

    Full Text Available An electronic signature uses a hash of message and an asymetrical algorithm of encryption for its generation. During verification of message on receiver side the hash of original message must be identical with the hash of received message. Electronic message is secured autentization of author and integrity of transmission date. By electronic signature it is possible to sign everything what is in digital form.

  16. Meteor signature interpretation

    Energy Technology Data Exchange (ETDEWEB)

    Canavan, G.H.

    1997-01-01

    Meteor signatures contain information about the constituents of space debris and present potential false alarms to early warnings systems. Better models could both extract the maximum scientific information possible and reduce their danger. Accurate predictions can be produced by models of modest complexity, which can be inverted to predict the sizes, compositions, and trajectories of object from their signatures for most objects of interest and concern.

  17. Motif-based embedding for graph clustering

    Science.gov (United States)

    Lim, Sungsu; Lee, Jae-Gil

    2016-12-01

    Community detection in complex networks is a fundamental problem that has been extensively studied owing to its wide range of applications. However, because community detection methods typically rely on the relations between vertices in networks, they may fail to discover higher-order graph substructures, called the network motifs. In this paper, we propose a novel embedding method for graph clustering that considers higher-order relationships involving multiple vertices. We show that our embedding method, which we call motif-based embedding, is more effective in detecting communities than existing graph embedding methods, spectral embedding and force-directed embedding, both theoretically and experimentally.

  18. Polyrhythmic synchronization in bursting networking motifs.

    Science.gov (United States)

    Shilnikov, Andrey; Gordon, René; Belykh, Igor

    2008-09-01

    We study the emergence of polyrhythmic dynamics of motifs which are the building block for small inhibitory-excitatory networks, such as central pattern generators controlling various locomotive behaviors of animals. We discover that the pacemaker determining the specific rhythm of such a network composed of realistic Hodgkin-Huxley-type neurons is identified through the order parameter, which is the ratio of the neurons' burst durations or of duty cycles. We analyze different configurations of the motifs and describe the universal mechanisms for synergetics of the bursting patterns. We discuss also the multistability of inhibitory networks that results in polyrhythmicity of its emergent synchronous behaviors. (c) 2008 American Institute of Physics.

  19. Book and library motif in Arabian Nights

    Directory of Open Access Journals (Sweden)

    Coşkun Polat

    2016-09-01

    In this book, it is aimed that using of book, library and literacy motifs and their conceptual meanings that could not be used in stories in any way have been tried to examine at Arabian Nights. As a result of the study carried out by considering the Arabian Nights, 52 nights that examine the book, reading, writing a book and writing in fiction have been determined. Thus, book, reading and library motifs are between the basic concepts given in the oeuvre. The content of the work is unique and useful for librarians and literati, historians and folklorists and all people.

  20. Signature verification: A comprehensive study of the hidden signature method

    Directory of Open Access Journals (Sweden)

    Putz-Leszczyńska Joanna

    2015-09-01

    Full Text Available Many handwritten signature verification algorithms have been developed in order to distinguish between genuine signatures and forgeries. An important group of these methods is based on dynamic time warping (DTW. Traditional use of DTW for signature verification consists in forming a misalignment score between the verified signature and a set of template signatures. The right selection of template signatures has a big impact on that verification. In this article, we describe our proposition for replacing the template signatures with the hidden signature-an artificial signature which is created by minimizing the mean misalignment between itself and the signatures from the enrollment set. We present a few hidden signature estimation methods together with their comprehensive comparison. The hidden signature opens a number of new possibilities for signature analysis. We apply statistical properties of the hidden signature to normalize the error signal of the verified signature and to use the misalignment on the normalized errors as a verification basis. A result, we achieve satisfying error rates that allow creating an on-line system, ready for operating in a real-world environment

  1. MEME SUITE: tools for motif discovery and searching.

    Science.gov (United States)

    Bailey, Timothy L; Boden, Mikael; Buske, Fabian A; Frith, Martin; Grant, Charles E; Clementi, Luca; Ren, Jingyuan; Li, Wilfred W; Noble, William S

    2009-07-01

    The MEME Suite web server provides a unified portal for online discovery and analysis of sequence motifs representing features such as DNA binding sites and protein interaction domains. The popular MEME motif discovery algorithm is now complemented by the GLAM2 algorithm which allows discovery of motifs containing gaps. Three sequence scanning algorithms--MAST, FIMO and GLAM2SCAN--allow scanning numerous DNA and protein sequence databases for motifs discovered by MEME and GLAM2. Transcription factor motifs (including those discovered using MEME) can be compared with motifs in many popular motif databases using the motif database scanning algorithm TOMTOM. Transcription factor motifs can be further analyzed for putative function by association with Gene Ontology (GO) terms using the motif-GO term association tool GOMO. MEME output now contains sequence LOGOS for each discovered motif, as well as buttons to allow motifs to be conveniently submitted to the sequence and motif database scanning algorithms (MAST, FIMO and TOMTOM), or to GOMO, for further analysis. GLAM2 output similarly contains buttons for further analysis using GLAM2SCAN and for rerunning GLAM2 with different parameters. All of the motif-based tools are now implemented as web services via Opal. Source code, binaries and a web server are freely available for noncommercial use at http://meme.nbcr.net.

  2. Identifying motifs in folktales using topic models

    NARCIS (Netherlands)

    Karsdorp, F.; Bosch, A.P.J. van den

    2013-01-01

    With the undertake of various folktale digitalization initiatives, the need for computational aids to explore these collections is increasing. In this paper we compare Labeled LDA (L-LDA) to a simple retrieval model on the task of identifying motifs in folktales. We show that both methods are well

  3. Highly scalable Ab initio genomic motif identification

    KAUST Repository

    Marchand, Benoit

    2011-01-01

    We present results of scaling an ab initio motif family identification system, Dragon Motif Finder (DMF), to 65,536 processor cores of IBM Blue Gene/P. DMF seeks groups of mutually similar polynucleotide patterns within a set of genomic sequences and builds various motif families from them. Such information is of relevance to many problems in life sciences. Prior attempts to scale such ab initio motif-finding algorithms achieved limited success. We solve the scalability issues using a combination of mixed-mode MPI-OpenMP parallel programming, master-slave work assignment, multi-level workload distribution, multi-level MPI collectives, and serial optimizations. While the scalability of our algorithm was excellent (94% parallel efficiency on 65,536 cores relative to 256 cores on a modest-size problem), the final speedup with respect to the original serial code exceeded 250,000 when serial optimizations are included. This enabled us to carry out many large-scale ab initio motiffinding simulations in a few hours while the original serial code would have needed decades of execution time. Copyright 2011 ACM.

  4. Discovery of protein phosphorylation motifs through exploratory data analysis.

    Directory of Open Access Journals (Sweden)

    Yi-Cheng Chen

    Full Text Available BACKGROUND: The need for efficient algorithms to uncover biologically relevant phosphorylation motifs has become very important with rapid expansion of the proteomic sequence database along with a plethora of new information on phosphorylation sites. Here we present a novel unsupervised method, called Motif Finder (in short, F-Motif for identification of phosphorylation motifs. F-Motif uses clustering of sequence information represented by numerical features that exploit the statistical information hidden in some foreground data. Furthermore, these identified motifs are then filtered to find "actual" motifs with statistically significant motif scores. RESULTS AND DISCUSSION: We have applied F-Motif to several new and existing data sets and compared its performance with two well known state-of-the-art methods. In almost all cases F-Motif could identify all statistically significant motifs extracted by the state-of-the-art methods. More importantly, in addition to this, F-Motif uncovers several novel motifs. We have demonstrated using clues from the literature that most of these new motifs discovered by F-Motif are indeed novel. We have also found some interesting phenomena. For example, for CK2 kinase, the conserved sites appear only on the right side of S. However, for CDK kinase, the adjacent site on the right of S is conserved with residue P. In addition, three different encoding methods, including a novel position contrast matrix (PCM and the simplest binary coding, are used and the ability of F-motif to discover motifs remains quite robust with respect to encoding schemes. CONCLUSIONS: An iterative algorithm proposed here uses exploratory data analysis to discover motifs from phosphorylated data. The effectiveness of F-Motif has been demonstrated using several real data sets as well as using a synthetic data set. The method is quite general in nature and can be used to find other types of motifs also. We have also provided a server for F-Motif

  5. Parallel motif extraction from very long sequences

    KAUST Repository

    Sahli, Majed

    2013-01-01

    Motifs are frequent patterns used to identify biological functionality in genomic sequences, periodicity in time series, or user trends in web logs. In contrast to a lot of existing work that focuses on collections of many short sequences, modern applications require mining of motifs in one very long sequence (i.e., in the order of several gigabytes). For this case, there exist statistical approaches that are fast but inaccurate; or combinatorial methods that are sound and complete. Unfortunately, existing combinatorial methods are serial and very slow. Consequently, they are limited to very short sequences (i.e., a few megabytes), small alphabets (typically 4 symbols for DNA sequences), and restricted types of motifs. This paper presents ACME, a combinatorial method for extracting motifs from a single very long sequence. ACME arranges the search space in contiguous blocks that take advantage of the cache hierarchy in modern architectures, and achieves almost an order of magnitude performance gain in serial execution. It also decomposes the search space in a smart way that allows scalability to thousands of processors with more than 90% speedup. ACME is the only method that: (i) scales to gigabyte-long sequences; (ii) handles large alphabets; (iii) supports interesting types of motifs with minimal additional cost; and (iv) is optimized for a variety of architectures such as multi-core systems, clusters in the cloud, and supercomputers. ACME reduces the extraction time for an exact-length query from 4 hours to 7 minutes on a typical workstation; handles 3 orders of magnitude longer sequences; and scales up to 16, 384 cores on a supercomputer. Copyright is held by the owner/author(s).

  6. DNA motif elucidation using belief propagation

    KAUST Repository

    Wong, Ka-Chun

    2013-06-29

    Protein-binding microarray (PBM) is a high-throughout platform that can measure the DNA-binding preference of a protein in a comprehensive and unbiased manner. A typical PBM experiment can measure binding signal intensities of a protein to all the possible DNA k-mers (k = 8 ?10); such comprehensive binding affinity data usually need to be reduced and represented as motif models before they can be further analyzed and applied. Since proteins can often bind to DNA in multiple modes, one of the major challenges is to decompose the comprehensive affinity data into multimodal motif representations. Here, we describe a new algorithm that uses Hidden Markov Models (HMMs) and can derive precise and multimodal motifs using belief propagations. We describe an HMM-based approach using belief propagations (kmerHMM), which accepts and preprocesses PBM probe raw data into median-binding intensities of individual k-mers. The k-mers are ranked and aligned for training an HMM as the underlying motif representation. Multiple motifs are then extracted from the HMM using belief propagations. Comparisons of kmerHMM with other leading methods on several data sets demonstrated its effectiveness and uniqueness. Especially, it achieved the best performance on more than half of the data sets. In addition, the multiple binding modes derived by kmerHMM are biologically meaningful and will be useful in interpreting other genome-wide data such as those generated from ChIP-seq. The executables and source codes are available at the authors\\' websites: e.g. http://www.cs.toronto.edu/?wkc/kmerHMM. 2013 The Author(s).

  7. Motifs, themes and thematic maps of an integrated Saccharomyces cerevisiae interaction network

    Directory of Open Access Journals (Sweden)

    Andrews Brenda

    2005-06-01

    Full Text Available Abstract Background Large-scale studies have revealed networks of various biological interaction types, such as protein-protein interaction, genetic interaction, transcriptional regulation, sequence homology, and expression correlation. Recurring patterns of interconnection, or 'network motifs', have revealed biological insights for networks containing either one or two types of interaction. Results To study more complex relationships involving multiple biological interaction types, we assembled an integrated Saccharomyces cerevisiae network in which nodes represent genes (or their protein products and differently colored links represent the aforementioned five biological interaction types. We examined three- and four-node interconnection patterns containing multiple interaction types and found many enriched multi-color network motifs. Furthermore, we showed that most of the motifs form 'network themes' – classes of higher-order recurring interconnection patterns that encompass multiple occurrences of network motifs. Network themes can be tied to specific biological phenomena and may represent more fundamental network design principles. Examples of network themes include a pair of protein complexes with many inter-complex genetic interactions – the 'compensatory complexes' theme. Thematic maps – networks rendered in terms of such themes – can simplify an otherwise confusing tangle of biological relationships. We show this by mapping the S. cerevisiae network in terms of two specific network themes. Conclusion Significantly enriched motifs in an integrated S. cerevisiae interaction network are often signatures of network themes, higher-order network structures that correspond to biological phenomena. Representing networks in terms of network themes provides a useful simplification of complex biological relationships.

  8. Mitochondrial and Y chromosome haplotype motifs as diagnostic markers of Jewish ancestry: a reconsideration.

    Directory of Open Access Journals (Sweden)

    Sergio eTofanelli

    2014-11-01

    Full Text Available Several authors have proposed haplotype motifs based on site variants at the mitochondrial genome (mtDNA and the non-recombining portion of the Y chromosome (NRY to trace the genealogies of Jewish people. Here, we analyzed their main approaches and test the feasibility of adopting motifs as ancestry markers through construction of a large database of mtDNA and NRY haplotypes from public genetic genealogical repositories. We verified the reliability of Jewish ancestry prediction based on the Cohen and Levite Modal Haplotypes in their classical 6 STR marker format or in the extended 12 STR format, as well as four founder mtDNA lineages (HVS-I segments accounting for about 40% of the current population of Ashkenazi Jews. For this purpose we compared haplotype composition in individuals of self-reported Jewish ancestry with the rest of European, African or Middle Eastern samples, to test for non-random association of ethno-geographic groups and haplotypes. Overall, NRY and mtDNA based motifs, previously reported to differentiate between groups, were found to be more represented in Jewish compared to non-Jewish groups. However, this seems to stem from common ancestors of Jewish lineages being rather recent respect to ancestors of non-Jewish lineages with the same haplotype signatures. Moreover, the polyphyly of haplotypes which contain the proposed motifs and the misuse of constant mutation rates heavily affected previous attempts to correctly dating the origin of common ancestries. Accordingly, our results stress the limitations of using the above haplotype motifs as reliable Jewish ancestry predictors and show its inadequacy for forensic or genealogical purposes.

  9. Ab initio coordination chemistry for nickel chelation motifs.

    Science.gov (United States)

    Sudan, R Jesu Jaya; Kumari, J Lesitha Jeeva; Sudandiradoss, C

    2015-01-01

    Chelation therapy is one of the most appreciated methods in the treatment of metal induced disease predisposition. Coordination chemistry provides a way to understand metal association in biological structures. In this work we have implemented coordination chemistry to study nickel coordination due to its high impact in industrial usage and thereby health consequences. This paper reports the analysis of nickel coordination from a large dataset of nickel bound structures and sequences. Coordination patterns predicted from the structures are reported in terms of donors, chelate length, coordination number, chelate geometry, structural fold and architecture. The analysis revealed histidine as the most favored residue in nickel coordination. The most common chelates identified were histidine based namely HHH, HDH, HEH and HH spaced at specific intervals. Though a maximum coordination number of 8 was observed, the presence of a single protein donor was noted to be mandatory in nickel coordination. The coordination pattern did not reveal any specific fold, nevertheless we report preferable residue spacing for specific structural architecture. In contrast, the analysis of nickel binding proteins from bacterial and archeal species revealed no common coordination patterns. Nickel binding sequence motifs were noted to be organism specific and protein class specific. As a result we identified about 13 signatures derived from 13 classes of nickel binding proteins. The specifications on nickel coordination presented in this paper will prove beneficial for developing better chelation strategies.

  10. Ab initio coordination chemistry for nickel chelation motifs.

    Directory of Open Access Journals (Sweden)

    R Jesu Jaya Sudan

    Full Text Available Chelation therapy is one of the most appreciated methods in the treatment of metal induced disease predisposition. Coordination chemistry provides a way to understand metal association in biological structures. In this work we have implemented coordination chemistry to study nickel coordination due to its high impact in industrial usage and thereby health consequences. This paper reports the analysis of nickel coordination from a large dataset of nickel bound structures and sequences. Coordination patterns predicted from the structures are reported in terms of donors, chelate length, coordination number, chelate geometry, structural fold and architecture. The analysis revealed histidine as the most favored residue in nickel coordination. The most common chelates identified were histidine based namely HHH, HDH, HEH and HH spaced at specific intervals. Though a maximum coordination number of 8 was observed, the presence of a single protein donor was noted to be mandatory in nickel coordination. The coordination pattern did not reveal any specific fold, nevertheless we report preferable residue spacing for specific structural architecture. In contrast, the analysis of nickel binding proteins from bacterial and archeal species revealed no common coordination patterns. Nickel binding sequence motifs were noted to be organism specific and protein class specific. As a result we identified about 13 signatures derived from 13 classes of nickel binding proteins. The specifications on nickel coordination presented in this paper will prove beneficial for developing better chelation strategies.

  11. Practical quantum digital signature

    Science.gov (United States)

    Yin, Hua-Lei; Fu, Yao; Chen, Zeng-Bing

    2016-03-01

    Guaranteeing nonrepudiation, unforgeability as well as transferability of a signature is one of the most vital safeguards in today's e-commerce era. Based on fundamental laws of quantum physics, quantum digital signature (QDS) aims to provide information-theoretic security for this cryptographic task. However, up to date, the previously proposed QDS protocols are impractical due to various challenging problems and most importantly, the requirement of authenticated (secure) quantum channels between participants. Here, we present the first quantum digital signature protocol that removes the assumption of authenticated quantum channels while remaining secure against the collective attacks. Besides, our QDS protocol can be practically implemented over more than 100 km under current mature technology as used in quantum key distribution.

  12. Factor models for cancer signatures

    Science.gov (United States)

    Kakushadze, Zura; Yu, Willie

    2016-11-01

    We present a novel method for extracting cancer signatures by applying statistical risk models (http://ssrn.com/abstract=2732453) from quantitative finance to cancer genome data. Using 1389 whole genome sequenced samples from 14 cancers, we identify an ;overall; mode of somatic mutational noise. We give a prescription for factoring out this noise and source code for fixing the number of signatures. We apply nonnegative matrix factorization (NMF) to genome data aggregated by cancer subtype and filtered using our method. The resultant signatures have substantially lower variability than those from unfiltered data. Also, the computational cost of signature extraction is cut by about a factor of 10. We find 3 novel cancer signatures, including a liver cancer dominant signature (96% contribution) and a renal cell carcinoma signature (70% contribution). Our method accelerates finding new cancer signatures and improves their overall stability. Reciprocally, the methods for extracting cancer signatures could have interesting applications in quantitative finance.

  13. Current signature sensor

    Science.gov (United States)

    Perotti, Jose M. (Inventor); Lucena, Angel (Inventor); Ihlefeld, Curtis (Inventor); Burns, Bradley (Inventor); Bassignani, Karin E. (Inventor)

    2005-01-01

    A solenoid health monitoring system uses a signal conditioner and controller assembly in one embodiment that includes analog circuitry and a DSP controller. The analog circuitry provides signal conditioning to the low-level raw signal coming from a signal acquisition assembly. Software running in a DSP analyzes the incoming data (recorded current signature) and determines the state of the solenoid whether it is energized, de-energized, or in a transitioning state. In one embodiment, the software identifies key features in the current signature during the transition phase and is able to determine the health of the solenoid.

  14. Using SCOPE to identify potential regulatory motifs in coregulated genes.

    Science.gov (United States)

    Martyanov, Viktor; Gross, Robert H

    2011-05-31

    SCOPE is an ensemble motif finder that uses three component algorithms in parallel to identify potential regulatory motifs by over-representation and motif position preference. Each component algorithm is optimized to find a different kind of motif. By taking the best of these three approaches, SCOPE performs better than any single algorithm, even in the presence of noisy data. In this article, we utilize a web version of SCOPE to examine genes that are involved in telomere maintenance. SCOPE has been incorporated into at least two other motif finding programs and has been used in other studies. The three algorithms that comprise SCOPE are BEAM, which finds non-degenerate motifs (ACCGGT), PRISM, which finds degenerate motifs (ASCGWT), and SPACER, which finds longer bipartite motifs (ACCnnnnnnnnGGT). These three algorithms have been optimized to find their corresponding type of motif. Together, they allow SCOPE to perform extremely well. Once a gene set has been analyzed and candidate motifs identified, SCOPE can look for other genes that contain the motif which, when added to the original set, will improve the motif score. This can occur through over-representation or motif position preference. Working with partial gene sets that have biologically verified transcription factor binding sites, SCOPE was able to identify most of the rest of the genes also regulated by the given transcription factor. Output from SCOPE shows candidate motifs, their significance, and other information both as a table and as a graphical motif map. FAQs and video tutorials are available at the SCOPE web site which also includes a "Sample Search" button that allows the user to perform a trial run. Scope has a very friendly user interface that enables novice users to access the algorithm's full power without having to become an expert in the bioinformatics of motif finding. As input, SCOPE can take a list of genes, or FASTA sequences. These can be entered in browser text fields, or read from

  15. Chiral Alkyl Halides: Underexplored Motifs in Medicine

    Directory of Open Access Journals (Sweden)

    Bálint Gál

    2016-11-01

    Full Text Available While alkyl halides are valuable intermediates in synthetic organic chemistry, their use as bioactive motifs in drug discovery and medicinal chemistry is rare in comparison. This is likely attributable to the common misconception that these compounds are merely non-specific alkylators in biological systems. A number of chlorinated compounds in the pharmaceutical and food industries, as well as a growing number of halogenated marine natural products showing unique bioactivity, illustrate the role that chiral alkyl halides can play in drug discovery. Through a series of case studies, we demonstrate in this review that these motifs can indeed be stable under physiological conditions, and that halogenation can enhance bioactivity through both steric and electronic effects. Our hope is that, by placing such compounds in the minds of the chemical community, they may gain more traction in drug discovery and inspire more synthetic chemists to develop methods for selective halogenation.

  16. Sequential motif profile of natural visibility graphs

    Science.gov (United States)

    Iacovacci, Jacopo; Lacasa, Lucas

    2016-11-01

    The concept of sequential visibility graph motifs—subgraphs appearing with characteristic frequencies in the visibility graphs associated to time series—has been advanced recently along with a theoretical framework to compute analytically the motif profiles associated to horizontal visibility graphs (HVGs). Here we develop a theory to compute the profile of sequential visibility graph motifs in the context of natural visibility graphs (VGs). This theory gives exact results for deterministic aperiodic processes with a smooth invariant density or stochastic processes that fulfill the Markov property and have a continuous marginal distribution. The framework also allows for a linear time numerical estimation in the case of empirical time series. A comparison between the HVG and the VG case (including evaluation of their robustness for short series polluted with measurement noise) is also presented.

  17. Statistical clumped isotope signatures

    NARCIS (Netherlands)

    Röckmann, T.; Popa, M.E.; Krol, M.C.; Hofmann, M.E.G.

    2016-01-01

    High precision measurements of molecules containing more than one heavy isotope may provide novel constraints on element cycles in nature. These so-called clumped isotope signatures are reported relative to the random (stochastic) distribution of heavy isotopes over all available isotopocules of

  18. Statistical clumped isotope signatures

    NARCIS (Netherlands)

    Röckmann, T.|info:eu-repo/dai/nl/304838233; Popa, M. E.|info:eu-repo/dai/nl/375806407; Krol, M. C.|info:eu-repo/dai/nl/078760410; Hofmann, M. E. G.|info:eu-repo/dai/nl/374642907

    2016-01-01

    High precision measurements of molecules containing more than one heavy isotope may provide novel constraints on element cycles in nature. These so-called clumped isotope signatures are reported relative to the random (stochastic) distribution of heavy isotopes over all available isotopocules of a

  19. Signatures of the Invisible

    CERN Multimedia

    Strom, D

    2003-01-01

    On the Net it is possible to take a look at art from afar via Virtual Museums. One such exhibition was recently in the New York Museum of Modern Art's branch, PS1. Entitled 'Signatures of the Invisible' it was a collaborative effort between artists and physicists (1/2 page).

  20. Chiral Alkyl Halides: Underexplored Motifs in Medicine

    OpenAIRE

    Bálint Gál; Cyril Bucher; Burns, Noah Z.

    2016-01-01

    While alkyl halides are valuable intermediates in synthetic organic chemistry, their use as bioactive motifs in drug discovery and medicinal chemistry is rare in comparison. This is likely attributable to the common misconception that these compounds are merely non-specific alkylators in biological systems. A number of chlorinated compounds in the pharmaceutical and food industries, as well as a growing number of halogenated marine natural products showing unique bioactivity, illustrate the r...

  1. Large-scale discovery of promoter motifs in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Thomas A Down

    2007-01-01

    Full Text Available A key step in understanding gene regulation is to identify the repertoire of transcription factor binding motifs (TFBMs that form the building blocks of promoters and other regulatory elements. Identifying these experimentally is very laborious, and the number of TFBMs discovered remains relatively small, especially when compared with the hundreds of transcription factor genes predicted in metazoan genomes. We have used a recently developed statistical motif discovery approach, NestedMICA, to detect candidate TFBMs from a large set of Drosophila melanogaster promoter regions. Of the 120 motifs inferred in our initial analysis, 25 were statistically significant matches to previously reported motifs, while 87 appeared to be novel. Analysis of sequence conservation and motif positioning suggested that the great majority of these discovered motifs are predictive of functional elements in the genome. Many motifs showed associations with specific patterns of gene expression in the D. melanogaster embryo, and we were able to obtain confident annotation of expression patterns for 25 of our motifs, including eight of the novel motifs. The motifs are available through Tiffin, a new database of DNA sequence motifs. We have discovered many new motifs that are overrepresented in D. melanogaster promoter regions, and offer several independent lines of evidence that these are novel TFBMs. Our motif dictionary provides a solid foundation for further investigation of regulatory elements in Drosophila, and demonstrates techniques that should be applicable in other species. We suggest that further improvements in computational motif discovery should narrow the gap between the set of known motifs and the total number of transcription factors in metazoan genomes.

  2. CONTEMPORARY USAGE OF TRADITIONAL TURKISH MOTIFS IN PRODUCT DESIGNS

    Directory of Open Access Journals (Sweden)

    Tulay Gumuser

    2012-12-01

    Full Text Available The aim of this study is to identify the traditional Turkish motifs and its relations among present industrial designs. Traditional Turkish motifs played a very important role in 16th century onwards. The arts of the Ottoman Empire were used because of their symbolic meanings and unique styles. When we examine these motifs we encounter; Tiger Stripe, Three Spot (Çintemani, Rumi, Hatayi, Penç, Cloud, Crescent, Star, Crown, Hyacinth, Tulip and Carnation motifs. Nowadays, Turkish designers have begun to use these traditional Turkish motifs in their designs so as to create differences and awareness in the world design. The examples of these industrial designs, using the Turkish motifs, have survived and have Ottoman heritage and historical value. In this study, the Turkish motifs will be examined along with their focus on contemporary Turkish industrial designs used today.

  3. MProfiler: A Profile-Based Method for DNA Motif Discovery

    Science.gov (United States)

    Altarawy, Doaa; Ismail, Mohamed A.; Ghanem, Sahar M.

    Motif Finding is one of the most important tasks in gene regulation which is essential in understanding biological cell functions. Based on recent studies, the performance of current motif finders is not satisfactory. A number of ensemble methods have been proposed to enhance the accuracy of the results. Existing ensemble methods overall performance is better than stand-alone motif finders. A recent ensemble method, MotifVoter, significantly outperforms all existing stand-alone and ensemble methods. In this paper, we propose a method, MProfiler, to increase the accuracy of MotifVoter without increasing the run time by introducing an idea called center profiling. Our experiments show improvement in the quality of generated clusters over MotifVoter in both accuracy and cluster compactness. Using 56 datasets, the accuracy of the final results using our method achieves 80% improvement in correlation coefficient nCC, and 93% improvement in performance coefficient nPC over MotifVoter.

  4. RNA structural motif recognition based on least-squares distance.

    Science.gov (United States)

    Shen, Ying; Wong, Hau-San; Zhang, Shaohong; Zhang, Lin

    2013-09-01

    RNA structural motifs are recurrent structural elements occurring in RNA molecules. RNA structural motif recognition aims to find RNA substructures that are similar to a query motif, and it is important for RNA structure analysis and RNA function prediction. In view of this, we propose a new method known as RNA Structural Motif Recognition based on Least-Squares distance (LS-RSMR) to effectively recognize RNA structural motifs. A test set consisting of five types of RNA structural motifs occurring in Escherichia coli ribosomal RNA is compiled by us. Experiments are conducted for recognizing these five types of motifs. The experimental results fully reveal the superiority of the proposed LS-RSMR compared with four other state-of-the-art methods.

  5. Chaotic motif sampler: detecting motifs from biological sequences by using chaotic neurodynamics

    Science.gov (United States)

    Matsuura, Takafumi; Ikeguchi, Tohru

    Identification of a region in biological sequences, motif extraction problem (MEP) is solved in bioinformatics. However, the MEP is an NP-hard problem. Therefore, it is almost impossible to obtain an optimal solution within a reasonable time frame. To find near optimal solutions for NP-hard combinatorial optimization problems such as traveling salesman problems, quadratic assignment problems, and vehicle routing problems, chaotic search, which is one of the deterministic approaches, has been proposed and exhibits better performance than stochastic approaches. In this paper, we propose a new alignment method that employs chaotic dynamics to solve the MEPs. It is called the Chaotic Motif Sampler. We show that the performance of the Chaotic Motif Sampler is considerably better than that of the conventional methods such as the Gibbs Site Sampler and the Neighborhood Optimization for Multiple Alignment Discovery.

  6. Assessing the Exceptionality of Coloured Motifs in Networks

    Directory of Open Access Journals (Sweden)

    Lacroix Vincent

    2009-01-01

    Full Text Available Various methods have been recently employed to characterise the structure of biological networks. In particular, the concept of network motif and the related one of coloured motif have proven useful to model the notion of a functional/evolutionary building block. However, algorithms that enumerate all the motifs of a network may produce a very large output, and methods to decide which motifs should be selected for downstream analysis are needed. A widely used method is to assess if the motif is exceptional, that is, over- or under-represented with respect to a null hypothesis. Much effort has been put in the last thirty years to derive -values for the frequencies of topological motifs, that is, fixed subgraphs. They rely either on (compound Poisson and Gaussian approximations for the motif count distribution in Erdös-Rényi random graphs or on simulations in other models. We focus on a different definition of graph motifs that corresponds to coloured motifs. A coloured motif is a connected subgraph with fixed vertex colours but unspecified topology. Our work is the first analytical attempt to assess the exceptionality of coloured motifs in networks without any simulation. We first establish analytical formulae for the mean and the variance of the count of a coloured motif in an Erdös-Rényi random graph model. Using simulations under this model, we further show that a Pólya-Aeppli distribution better approximates the distribution of the motif count compared to Gaussian or Poisson distributions. The Pólya-Aeppli distribution, and more generally the compound Poisson distributions, are indeed well designed to model counts of clumping events. Altogether, these results enable to derive a -value for a coloured motif, without spending time on simulations.

  7. DEKONSTRUKSI MOTIF BATIK KERATON CIREBON: PENGARUH RAGAM HIAS KERATON PADA MOTIF BATIK CIREBON

    Directory of Open Access Journals (Sweden)

    Agus Nursalim

    2015-04-01

    Full Text Available Motif batik Keraton Cirebon memiliki makna simbolik dan filosofis yang mengandung pesan moral. Ide dasar batik keraton adalah dari ragam hias Keraton Cirebon, naskah dan mushaf Al-qur’an pada Abad 20. Tekanan dan resistensi kebudayaan barat pada dekade 70-an yang bersifat progresif utopis telah mengubur berbagai tradisi dan kebudayaan etnik, identitas lokal, subculture, yang dianggap tidak sesuai dengan semangat zaman modern. Arus informasi global telah memperkaya cakrawala pengetahuan lokal yang mampu membangkitkan kesadaran lokal yaitu kesadaran ontologism diantara kebudayaan plural yang imperialis dan represif yang akan menggiring pada krisis identitas. Identitas, menurut Jonathan Rutherfort merupakan satu mata rantai masa lalu dengan hubunganhubungan sosial, kultural, dan ekonomi di dalam ruang dan waktu satu masyarakat hidup. Kini motif batik keraton telah menjadi identitas batik Cirebon. Penelitian ini bersifat diskriptif kualitatif yang mengkaji hingar bingarnya era kebangkitan kembali motif batik keraton Cirebon setelah mengalami ‘mati suri’ selama berpuluh-puluh tahun. Permasalahannya adalah: Bagaimana pola ragam hias Keraton Cirebon mengalami dekonstruksi menjadi motif batik keraton Cirebon? Apakah makna filosofis dan makna simbolik motif Batik Keraton mengalami dekonstruksi setelah berkembang pesat menjadi batik Cirebon? Teknik Pengumpulan data dilakukan dengan cara: observasi, wawancara dan dokumentasi. Sedangkan Analisis data hasil penelitian dilakukan dengan pendekatan teori ‘semiotika dekonstruktif’ dari Jaques Derida dan Ferdinand de’Sausure. Kajian terhadap bahasa dan makna (petanda simbolik dilakukan dengan teorinya Ferdinand de’Saussure. Sedangkan; penafsiran makna ‘logos’ menggunakan pendekatan teori semiotika dekonstruktif Jaques Derida. Dari hasil penelitian diperoleh informasi secara akurat dan benar mengenai proses dekonstruksi bentuk ragam hias ke dalam motif batik keraton hingga menjadi

  8. The MHC motif viewer: a visualization tool for MHC binding motifs

    DEFF Research Database (Denmark)

    Rapin, Nicolas; Hoof, Ilka; Lund, Ole

    2010-01-01

    In vertebrates, the onset of cellular immune reactions is controlled by presentation of peptides in complex with major histocompatibility complex (MHC) molecules to T cell receptors. In humans, MHCs are called human leukocyte antigens (HLAs). Different MHC molecules present different subsets...... is hampered by the lack of tools for browsing and comparing specificity of these molecules. We have developed a Web server, MHC Motif Viewer, which allows the display of the binding motif for MHC class I proteins for human, chimpanzee, rhesus monkey, mouse, and swine, as well as HLA-DR protein sequences...

  9. Multilayer motif analysis of brain networks

    Science.gov (United States)

    Battiston, Federico; Nicosia, Vincenzo; Chavez, Mario; Latora, Vito

    2017-04-01

    In the last decade, network science has shed new light both on the structural (anatomical) and on the functional (correlations in the activity) connectivity among the different areas of the human brain. The analysis of brain networks has made possible to detect the central areas of a neural system and to identify its building blocks by looking at overabundant small subgraphs, known as motifs. However, network analysis of the brain has so far mainly focused on anatomical and functional networks as separate entities. The recently developed mathematical framework of multi-layer networks allows us to perform an analysis of the human brain where the structural and functional layers are considered together. In this work, we describe how to classify the subgraphs of a multiplex network, and we extend the motif analysis to networks with an arbitrary number of layers. We then extract multi-layer motifs in brain networks of healthy subjects by considering networks with two layers, anatomical and functional, respectively, obtained from diffusion and functional magnetic resonance imaging. Results indicate that subgraphs in which the presence of a physical connection between brain areas (links at the structural layer) coexists with a non-trivial positive correlation in their activities are statistically overabundant. Finally, we investigate the existence of a reinforcement mechanism between the two layers by looking at how the probability to find a link in one layer depends on the intensity of the connection in the other one. Showing that functional connectivity is non-trivially constrained by the underlying anatomical network, our work contributes to a better understanding of the interplay between the structure and function in the human brain.

  10. Presence of a consensus DNA motif at nearby DNA sequence of the mutation susceptible CG nucleotides.

    Science.gov (United States)

    Chowdhury, Kaushik; Kumar, Suresh; Sharma, Tanu; Sharma, Ankit; Bhagat, Meenakshi; Kamai, Asangla; Ford, Bridget M; Asthana, Shailendra; Mandal, Chandi C

    2018-01-10

    Complexity in tissues affected by cancer arises from somatic mutations and epigenetic modifications in the genome. The mutation susceptible hotspots present within the genome indicate a non-random nature and/or a position specific selection of mutation. An association exists between the occurrence of mutations and epigenetic DNA methylation. This study is primarily aimed at determining mutation status, and identifying a signature for predicting mutation prone zones of tumor suppressor (TS) genes. Nearby sequences from the top five positions having a higher mutation frequency in each gene of 42 TS genes were selected from a cosmic database and were considered as mutation prone zones. The conserved motifs present in the mutation prone DNA fragments were identified. Molecular docking studies were done to determine putative interactions between the identified conserved motifs and enzyme methyltransferase DNMT1. Collective analysis of 42 TS genes found GC as the most commonly replaced and AT as the most commonly formed residues after mutation. Analysis of the top 5 mutated positions of each gene (210 DNA segments for 42 TS genes) identified that CG nucleotides of the amino acid codons (e.g., Arginine) are most susceptible to mutation, and found a consensus DNA "T/AGC/GAGGA/TG" sequence present in these mutation prone DNA segments. Similar to TS genes, analysis of 54 oncogenes not only found CG nucleotides of the amino acid Arg as the most susceptible to mutation, but also identified the presence of similar consensus DNA motifs in the mutation prone DNA fragments (270 DNA segments for 54 oncogenes) of oncogenes. Docking studies depicted that, upon binding of DNMT1 methylates to this consensus DNA motif (C residues of CpG islands), mutation was likely to occur. Thus, this study proposes that DNMT1 mediated methylation in chromosomal DNA may decrease if a foreign DNA segment containing this consensus sequence along with CG nucleotides is exogenously introduced to dividing

  11. RMOD: a tool for regulatory motif detection in signaling network.

    Directory of Open Access Journals (Sweden)

    Jinki Kim

    Full Text Available Regulatory motifs are patterns of activation and inhibition that appear repeatedly in various signaling networks and that show specific regulatory properties. However, the network structures of regulatory motifs are highly diverse and complex, rendering their identification difficult. Here, we present a RMOD, a web-based system for the identification of regulatory motifs and their properties in signaling networks. RMOD finds various network structures of regulatory motifs by compressing the signaling network and detecting the compressed forms of regulatory motifs. To apply it into a large-scale signaling network, it adopts a new subgraph search algorithm using a novel data structure called path-tree, which is a tree structure composed of isomorphic graphs of query regulatory motifs. This algorithm was evaluated using various sizes of signaling networks generated from the integration of various human signaling pathways and it showed that the speed and scalability of this algorithm outperforms those of other algorithms. RMOD includes interactive analysis and auxiliary tools that make it possible to manipulate the whole processes from building signaling network and query regulatory motifs to analyzing regulatory motifs with graphical illustration and summarized descriptions. As a result, RMOD provides an integrated view of the regulatory motifs and mechanism underlying their regulatory motif activities within the signaling network. RMOD is freely accessible online at the following URL: http://pks.kaist.ac.kr/rmod.

  12. RMOD: a tool for regulatory motif detection in signaling network.

    Science.gov (United States)

    Kim, Jinki; Yi, Gwan-Su

    2013-01-01

    Regulatory motifs are patterns of activation and inhibition that appear repeatedly in various signaling networks and that show specific regulatory properties. However, the network structures of regulatory motifs are highly diverse and complex, rendering their identification difficult. Here, we present a RMOD, a web-based system for the identification of regulatory motifs and their properties in signaling networks. RMOD finds various network structures of regulatory motifs by compressing the signaling network and detecting the compressed forms of regulatory motifs. To apply it into a large-scale signaling network, it adopts a new subgraph search algorithm using a novel data structure called path-tree, which is a tree structure composed of isomorphic graphs of query regulatory motifs. This algorithm was evaluated using various sizes of signaling networks generated from the integration of various human signaling pathways and it showed that the speed and scalability of this algorithm outperforms those of other algorithms. RMOD includes interactive analysis and auxiliary tools that make it possible to manipulate the whole processes from building signaling network and query regulatory motifs to analyzing regulatory motifs with graphical illustration and summarized descriptions. As a result, RMOD provides an integrated view of the regulatory motifs and mechanism underlying their regulatory motif activities within the signaling network. RMOD is freely accessible online at the following URL: http://pks.kaist.ac.kr/rmod.

  13. UKIRAN KERAWANG ACEH GAYO SEBAGAI INSPIRASI PENCIPTAAN MOTIF BATIK KHAS GAYO

    Directory of Open Access Journals (Sweden)

    Irfa ina Rohana Salma

    2016-12-01

    Full Text Available ABSTRAK Industri batik mulai berkembang di Gayo, tetapi belum memiliki motif batik khas daerah. Oleh karena itu perlu diciptakan motif batik khas Gayo, dengan mengambil inspirasi dari ukiran yang terdapat pada rumah tradisional yang biasa disebut ukiran kerawang Gayo. Tujuan penciptaan seni ini adalah untuk menciptakan motif batik yang memiliki ciri khas Gayo. Metode yang digunakan yaitu eksplorasi ide, perancangan, dan perwujudan menjadi motif batik. Dalam kegiatan ini telah diciptakan enam motif batik khas Gayo yaitu: (1 Motif Ceplok Gayo; (2 Motif Gayo Tegak; (3 Motif Gayo Lurus; (4 Motif Parang Gayo; (5 Motif Gayo Lembut; dan (6 Motif Geometris Gayo. Hasil uji kesukaan terhadap motif kepada lima puluh responden menunjukkan bahwa Motif Ceplok Gayo paling banyak dipilih oleh responden yaitu sebesar 19%, sedangkan Motif Parang Gayo 18%, Motif Gayo Lembut 17%, Motif Geometris Gayo 17%, Motif Gayo Lurus 15% dan Motif Gayo Tegak 14%. Rata-rata motif yang dihasilkan mendapatkan apresiasi yang baik dari responden, sehingga semua motif layak diproduksi sebagai batik khas Gayo.Kata kunci: batik Gayo, Motif Ceplok Gayo, Motif Parang Gayo.ABSTRACTBatik industry began to develop in Gayo, but have not had a typical batik motif itself. Therefore, it is necessary to create batik motifs of Gayo, by taking inspiration from the carvings found in traditional houses commonly called kerawang Gayo. The purpose of this art is to create motifs those have a Gayo characteristic. The method used are the idea exploration, design, and motifs embodiment. In this activity has created six Gayo batik motifs, namely: (1 Motif Ceplok Gayo; (2 Motif Gayo Tegak; (3 Motif GayoLurus; (4 Motif Parang Gayo; (5 Motif Gayo Lembut; dan (6 Motif Geometris Gayo. The test results fondness of the motives to fifty respondents indicated that the Motif Ceplok Gayo most preferred by respondents ie 19%, while Motif Parang Gayo 18%, Motif Gayo Lembut 17%, Motif Geometris Gayo 17%, Motif Gayo

  14. Promoter Motifs in NCLDVs: An Evolutionary Perspective

    Directory of Open Access Journals (Sweden)

    Graziele Pereira Oliveira

    2017-01-01

    Full Text Available For many years, gene expression in the three cellular domains has been studied in an attempt to discover sequences associated with the regulation of the transcription process. Some specific transcriptional features were described in viruses, although few studies have been devoted to understanding the evolutionary aspects related to the spread of promoter motifs through related viral families. The discovery of giant viruses and the proposition of the new viral order Megavirales that comprise a monophyletic group, named nucleo-cytoplasmic large DNA viruses (NCLDV, raised new questions in the field. Some putative promoter sequences have already been described for some NCLDV members, bringing new insights into the evolutionary history of these complex microorganisms. In this review, we summarize the main aspects of the transcription regulation process in the three domains of life, followed by a systematic description of what is currently known about promoter regions in several NCLDVs. We also discuss how the analysis of the promoter sequences could bring new ideas about the giant viruses’ evolution. Finally, considering a possible common ancestor for the NCLDV group, we discussed possible promoters’ evolutionary scenarios and propose the term “MEGA-box” to designate an ancestor promoter motif (‘TATATAAAATTGA’ that could be evolved gradually by nucleotides’ gain and loss and point mutations.

  15. An Affinity Propagation-Based DNA Motif Discovery Algorithm

    Directory of Open Access Journals (Sweden)

    Chunxiao Sun

    2015-01-01

    Full Text Available The planted (l,d motif search (PMS is one of the fundamental problems in bioinformatics, which plays an important role in locating transcription factor binding sites (TFBSs in DNA sequences. Nowadays, identifying weak motifs and reducing the effect of local optimum are still important but challenging tasks for motif discovery. To solve the tasks, we propose a new algorithm, APMotif, which first applies the Affinity Propagation (AP clustering in DNA sequences to produce informative and good candidate motifs and then employs Expectation Maximization (EM refinement to obtain the optimal motifs from the candidate motifs. Experimental results both on simulated data sets and real biological data sets show that APMotif usually outperforms four other widely used algorithms in terms of high prediction accuracy.

  16. An Affinity Propagation-Based DNA Motif Discovery Algorithm.

    Science.gov (United States)

    Sun, Chunxiao; Huo, Hongwei; Yu, Qiang; Guo, Haitao; Sun, Zhigang

    2015-01-01

    The planted (l, d) motif search (PMS) is one of the fundamental problems in bioinformatics, which plays an important role in locating transcription factor binding sites (TFBSs) in DNA sequences. Nowadays, identifying weak motifs and reducing the effect of local optimum are still important but challenging tasks for motif discovery. To solve the tasks, we propose a new algorithm, APMotif, which first applies the Affinity Propagation (AP) clustering in DNA sequences to produce informative and good candidate motifs and then employs Expectation Maximization (EM) refinement to obtain the optimal motifs from the candidate motifs. Experimental results both on simulated data sets and real biological data sets show that APMotif usually outperforms four other widely used algorithms in terms of high prediction accuracy.

  17. Probabilistic models for semisupervised discriminative motif discovery in DNA sequences.

    Science.gov (United States)

    Kim, Jong Kyoung; Choi, Seungjin

    2011-01-01

    Methods for discriminative motif discovery in DNA sequences identify transcription factor binding sites (TFBSs), searching only for patterns that differentiate two sets (positive and negative sets) of sequences. On one hand, discriminative methods increase the sensitivity and specificity of motif discovery, compared to generative models. On the other hand, generative models can easily exploit unlabeled sequences to better detect functional motifs when labeled training samples are limited. In this paper, we develop a hybrid generative/discriminative model which enables us to make use of unlabeled sequences in the framework of discriminative motif discovery, leading to semisupervised discriminative motif discovery. Numerical experiments on yeast ChIP-chip data for discovering DNA motifs demonstrate that the best performance is obtained between the purely-generative and the purely-discriminative and the semisupervised learning improves the performance when labeled sequences are limited.

  18. MADMX: A Novel Strategy for Maximal Dense Motif Extraction

    Science.gov (United States)

    Grossi, Roberto; Pietracaprina, Andrea; Pisanti, Nadia; Pucci, Geppino; Upfal, Eli; Vandin, Fabio

    We develop, analyze and experiment with a new tool, called madmx, which extracts frequent motifs, possibly including don’t care characters, from biological sequences. We introduce density, a simple and flexible measure for bounding the number of don’t cares in a motif, defined as the ratio of solid (i.e., different from don’t care) characters to the total length of the motif. By extracting only maximal dense motifs, madmx reduces the output size and improves performance, while enhancing the quality of the discoveries. The efficiency of our approach relies on a newly defined combining operation, dubbed fusion, which allows for the construction of maximal dense motifs in a bottom-up fashion, while avoiding the generation of nonmaximal ones. We provide experimental evidence of the efficiency and the quality of the motifs returned by madmx.

  19. Parole, Sintagmatik, dan Paradigmatik Motif Batik Mega Mendung

    Directory of Open Access Journals (Sweden)

    Rudi - Nababan

    2012-04-01

    Full Text Available ABSTRACT   Discussing traditional batik is related a lot to the organization system of fine arts element ac- companying it, either the pattern of the motif or the technique of the making. In this case, the motif of Mega Mendung Cirebon certainly has patterns and rules which are traditionally different from the other motifs in other areas. Through  semiotics analysis especially with Saussure and Pierce concept, it can be traced that batik with Cirebon motif, in this case Mega Mendung motif, has parole and langue system, as unique fine arts language in batik, and structure of visual syntagmatic and paradigmatic. In the context of batik motif as fine arts language, it is surely related to sign system as symbol and icon.       Keywords: visual semiotic, Cirebon’s batik.

  20. Signatures of topological superconductivity

    Energy Technology Data Exchange (ETDEWEB)

    Peng, Yang

    2017-07-19

    The prediction and experimental discovery of topological insulators brought the importance of topology in condensed matter physics into the limelight. Topology hence acts as a new dimension along which more and more new states of matter start to emerge. One of these topological states of matter, namely topological superconductors, comes into the focus because of their gapless excitations. These gapless excitations, especially in one dimensional topological superconductors, are Majorana zero modes localized at the ends of the superconductor and exhibit exotic nonabelian statistics, which can be potentially applied to fault-tolerant quantum computation. Given their highly interesting physical properties and potential applications to quantum computation, both theorists and experimentalists spend great efforts to realize topological supercondoctors and to detect Majoranas. In two projects within this thesis, we investigate the properties of Majorana zero modes in realistic materials which are absent in simple theoretical models. We find that the superconducting proximity effect, an essential ingredient in all existing platforms for topological superconductors, plays a significant role in determining the localization property of the Majoranas. Strong proximity coupling between the normal system and the superconducting substrate can lead to strongly localized Majoranas, which can explain the observation in a recent experiment. Motivated by experiments in Molenkamp's group, we also look at realistic quantum spin Hall Josephson junctions, in which charge puddles acting as magnetic impurities are coupled to the helical edge states. We find that with this setup, the junction generically realizes an exotic 8π periodic Josephson effect, which is absent in a pristine Josephson junction. In another two projects, we propose more pronounced signatures of Majoranas that are accessible with current experimental techniques. The first one is a transport measurement, which uses

  1. Why is the GMN motif conserved in the CorA/Mrs2/Alr1 superfamily of magnesium transport proteins?

    Science.gov (United States)

    Palombo, Isolde; Daley, Daniel O; Rapp, Mikaela

    2013-07-16

    Members of the CorA/Mrs2/Alr1 superfamily of transport proteins mediate magnesium uptake in all kingdoms of life. Family members have a low degree of sequence conservation but are characterized by a conserved extracellular loop. While the degree of sequence conservation in the loop deviates to some extent between family members, the GMN family signature motif is always present. Structural and functional data imply that the loop plays a central role in magnesium selectivity, and recent biochemical data suggest it is crucial for stabilizing the pentamer in the magnesium-free (putative open) conformation. In this study, we present a detailed structure-function analysis of the extracellular loop of CorA from Thermotoga maritima, which provides molecular insight into how the loop mediates these two functions. The data show that loop residues outside of the GMN motif can be substituted if they support the pentameric state, but the residues of the GMN motif are intolerant to substitution. We conclude that G(312) is absolutely required for magnesium uptake, M(313) is absolutely required for pentamer integrity in the putative open conformation, and N(314) plays a role in both of these functions. These observations suggest a molecular reason why the GMN motif is conserved throughout the CorA/Mrs2/Alr1 superfamily.

  2. Detecting DNA regulatory motifs by incorporating positional trendsin information content

    Energy Technology Data Exchange (ETDEWEB)

    Kechris, Katherina J.; van Zwet, Erik; Bickel, Peter J.; Eisen,Michael B.

    2004-05-04

    On the basis of the observation that conserved positions in transcription factor binding sites are often clustered together, we propose a simple extension to the model-based motif discovery methods. We assign position-specific prior distributions to the frequency parameters of the model, penalizing deviations from a specified conservation profile. Examples with both simulated and real data show that this extension helps discover motifs as the data become noisier or when there is a competing false motif.

  3. An Affinity Propagation-Based DNA Motif Discovery Algorithm

    OpenAIRE

    Chunxiao Sun; Hongwei Huo; Qiang Yu; Haitao Guo; Zhigang Sun

    2015-01-01

    The planted (l, d) motif search (PMS) is one of the fundamental problems in bioinformatics, which plays an important role in locating transcription factor binding sites (TFBSs) in DNA sequences. Nowadays, identifying weak motifs and reducing the effect of local optimum are still important but challenging tasks for motif discovery. To solve the tasks, we propose a new algorithm, APMotif, which first applies the Affinity Propagation (AP) clustering in DNA sequences to produce informative and go...

  4. Motif content comparison between monocot and dicot species.

    Science.gov (United States)

    Cserhati, Matyas

    2015-03-01

    While a number of DNA sequence motifs have been functionally characterized, the full repertoire of motifs in an organism (the motifome) is yet to be characterized. The present study wishes to widen the scope of motif content analysis in different monocot and dicot species that include both rice species, Brachypodium, corn, wheat as monocots and Arabidopsis, Lotus japonica, Medicago truncatula, and Populus tremula as dicots. All possible existing motifs were analyzed in different regions of genomes such as were found in different sets of sequences in these species: the whole genome, core proximal and distal promoters, 5' and 3' UTRs, and the 1st introns. Due to the increased number of species involved in this study compared to previous works, species relationships were analyzed based on the similarity of common motif content. Certain secondary structure elements were inferred in the genomes of these species as well as new unknown motifs. The distribution of 20 motifs common to the studied species were found to have a significantly larger occurrence within the promoters and 3' UTRs of genes, both being regulatory regions. Motifs common to the promoter regions of japonica rice, Brachypodium, and corn were also found in a number of orthologous and paralogous genes. Some of our motifs were found to be complementary to miRNA elements in Brachypodium distachyon and japonica rice.

  5. STEME: a robust, accurate motif finder for large data sets.

    Directory of Open Access Journals (Sweden)

    John E Reid

    Full Text Available Motif finding is a difficult problem that has been studied for over 20 years. Some older popular motif finders are not suitable for analysis of the large data sets generated by next-generation sequencing. We recently published an efficient approximation (STEME to the EM algorithm that is at the core of many motif finders such as MEME. This approximation allows the EM algorithm to be applied to large data sets. In this work we describe several efficient extensions to STEME that are based on the MEME algorithm. Together with the original STEME EM approximation, these extensions make STEME a fully-fledged motif finder with similar properties to MEME. We discuss the difficulty of objectively comparing motif finders. We show that STEME performs comparably to existing prominent discriminative motif finders, DREME and Trawler, on 13 sets of transcription factor binding data in mouse ES cells. We demonstrate the ability of STEME to find long degenerate motifs which these discriminative motif finders do not find. As part of our method, we extend an earlier method due to Nagarajan et al. for the efficient calculation of motif E-values. STEME's source code is available under an open source license and STEME is available via a web interface.

  6. Clustering signatures classify directed networks

    Science.gov (United States)

    Ahnert, S. E.; Fink, T. M. A.

    2008-09-01

    We use a clustering signature, based on a recently introduced generalization of the clustering coefficient to directed networks, to analyze 16 directed real-world networks of five different types: social networks, genetic transcription networks, word adjacency networks, food webs, and electric circuits. We show that these five classes of networks are cleanly separated in the space of clustering signatures due to the statistical properties of their local neighborhoods, demonstrating the usefulness of clustering signatures as a classifier of directed networks.

  7. Electronic Warfare Signature Measurement Facility

    Data.gov (United States)

    Federal Laboratory Consortium — The Electronic Warfare Signature Measurement Facility contains specialized mobile spectral, radiometric, and imaging measurement systems to characterize ultraviolet,...

  8. Expressiveness considerations of XML signatures

    DEFF Research Database (Denmark)

    Jensen, Meiko; Meyer, Christopher

    2011-01-01

    XML Signatures are used to protect XML-based Web Service communication against a broad range of attacks related to man-in-the-middle scenarios. However, due to the complexity of the Web Services specification landscape, the task of applying XML Signatures in a robust and reliable manner becomes...... more and more challenging. In this paper, we investigate this issue, describing how an attacker can still interfere with Web Services communication even in the presence of XML Signatures. Additionally, we discuss the interrelation of XML Signatures and XML Encryption, focussing on their security...

  9. Transnationalism as a motif in family stories.

    Science.gov (United States)

    Stone, Elizabeth; Gomez, Erica; Hotzoglou, Despina; Lipnitsky, Jane Y

    2005-12-01

    Family stories have long been recognized as a vehicle for assessing components of a family's emotional and social life, including the degree to which an immigrant family has been willing to assimilate. Transnationalism, defined as living in one or more cultures and maintaining connections to both, is now increasingly common. A qualitative study of family stories in the family of those who appear completely "American" suggests that an affiliation with one's home country is nevertheless detectable in the stories via motifs such as (1) positively connotated home remedies, (2) continuing denigration of home country "enemies," (3) extensive knowledge of the home country history and politics, (4) praise of endogamy and negative assessment of exogamy, (5) superiority of home country to America, and (6) beauty of home country. Furthermore, an awareness of which model--assimilationist or transnational--governs a family's experience may help clarify a clinician's understanding of a family's strengths, vulnerabilities, and mode of framing their cultural experiences.

  10. Rekayasa Pengembangan Desain Motif Batik Khas Melayu

    Directory of Open Access Journals (Sweden)

    Eustasia Sri Murwati

    2016-04-01

    Full Text Available ABSTRAKPengembangan desain batik melalui rancang bangun perekayasaan desain menurut ragam hias Melayu meliputi pengembangan motif dan proses, termasuk pemilihan komposisi warna. Proses yang sering dilakukan yaitu proses celup, penghilangan lilin dan celup warna tumpangan atau proses colet, celup, penghilangan lilin atau celup kemudian penghilangan lilin yang disebut Batik Kelengan. Setiap pulau di Indonesia mempunyai ciri khas budaya dan kesenian yang dikenal dengan corak/ragam hias khas daerah, juga ornamen yang diminati oleh masyarakat dari daerah tersebut atau dari daerah lain. Kondisi demikian mendorong pertumbuhan industri kerajinan yang memanfaatkan unsur–unsur seni. Adapun motif yang diperoleh adalah: Ayam Berlaga, Bungo Matahari, Kuntum Bersanding, Lancang Kuning, Encong Kerinci, Durian Pecah, Bungo Bintang, Bungo Pauh Kecil, Riang-riang, Bungo Nagaro. Pengembangan desain tersebut dipilih 3 produk terbaik yang dinilai oleh 5 penilai yang ahli di bidang desain batik, yaitu motif Durian Pecah, Ayam Berlaga, dan Bungo Matahari. Rancang bangun diversifikasi desain dengan memanfaatkan unsur–unsur seni dan ketrampilan etnis Melayu yaitu pemilihan ragam hias dan motif batik Melayu untuk diterapkan ke bahan sandang dengan komposisi warna yang menarik, sehingga produk memenuhi selera konsumen. Memperbaiki keberagaman batik dengan meningkatkan desain produk antara lain menuangkan ragam hias Melayu ke dalam proses batik yang menggunakan berbagai macam warna sehingga komposisi warna memadai. Diperoleh hasil produk batik dengan ragam hias Melayu yang berkualitas dan komposisi warna yang sesuai dengan karakter ragam hias Melayu. Rancang bangun desain produk untuk mendapatkan formulasi desain serta kelayakan prosesnya dengan penekanan pada teknologi akrab lingkungan dilaksanakan dengan alternatif pendekatan yaitu penciptaan desain bentuk baru.Kata kunci: desain, batik, rancang bangun, ragam hias, MelayuABSTRACTDevelopment of batik design through

  11. Motif-role-fingerprints: the building-blocks of motifs, clustering-coefficients and transitivities in directed networks.

    Directory of Open Access Journals (Sweden)

    Mark D McDonnell

    Full Text Available Complex networks are frequently characterized by metrics for which particular subgraphs are counted. One statistic from this category, which we refer to as motif-role fingerprints, differs from global subgraph counts in that the number of subgraphs in which each node participates is counted. As with global subgraph counts, it can be important to distinguish between motif-role fingerprints that are 'structural' (induced subgraphs and 'functional' (partial subgraphs. Here we show mathematically that a vector of all functional motif-role fingerprints can readily be obtained from an arbitrary directed adjacency matrix, and then converted to structural motif-role fingerprints by multiplying that vector by a specific invertible conversion matrix. This result demonstrates that a unique structural motif-role fingerprint exists for any given functional motif-role fingerprint. We demonstrate a similar result for the cases of functional and structural motif-fingerprints without node roles, and global subgraph counts that form the basis of standard motif analysis. We also explicitly highlight that motif-role fingerprints are elemental to several popular metrics for quantifying the subgraph structure of directed complex networks, including motif distributions, directed clustering coefficient, and transitivity. The relationships between each of these metrics and motif-role fingerprints also suggest new subtypes of directed clustering coefficients and transitivities. Our results have potential utility in analyzing directed synaptic networks constructed from neuronal connectome data, such as in terms of centrality. Other potential applications include anomaly detection in networks, identification of similar networks and identification of similar nodes within networks. Matlab code for calculating all stated metrics following calculation of functional motif-role fingerprints is provided as S1 Matlab File.

  12. Motif decomposition of the phosphotyrosine proteome reveals a new N-terminal binding motif for SHIP2

    DEFF Research Database (Denmark)

    Miller, Martin Lee; Hanke, S.; Hinsby, A. M.

    2008-01-01

    (P)-specific binding partners for peptides corresponding to the extracted motifs. We confirmed numerous previously known interaction motifs and found 15 new interactions mediated by phosphosites not previously known to bind SH2 or PTB. Remarkably, a novel hydrophobic N-terminal motif ((L/V/I)(L/V/I)pY) was identified...... and validated as a binding motif for the SH2 domain-containing inositol phosphatase SHIP2. Our decomposition of the in vivo Tyr(P) proteome furthermore suggests that two-thirds of the Tyr(P) sites mediate interaction, whereas the remaining third govern processes such as enzyme activation and nucleic acid...

  13. The limits of de novo DNA motif discovery.

    Science.gov (United States)

    Simcha, David; Price, Nathan D; Geman, Donald

    2012-01-01

    A major challenge in molecular biology is reverse-engineering the cis-regulatory logic that plays a major role in the control of gene expression. This program includes searching through DNA sequences to identify "motifs" that serve as the binding sites for transcription factors or, more generally, are predictive of gene expression across cellular conditions. Several approaches have been proposed for de novo motif discovery-searching sequences without prior knowledge of binding sites or nucleotide patterns. However, unbiased validation is not straightforward. We consider two approaches to unbiased validation of discovered motifs: testing the statistical significance of a motif using a DNA "background" sequence model to represent the null hypothesis and measuring performance in predicting membership in gene clusters. We demonstrate that the background models typically used are "too null," resulting in overly optimistic assessments of significance, and argue that performance in predicting TF binding or expression patterns from DNA motifs should be assessed by held-out data, as in predictive learning. Applying this criterion to common motif discovery methods resulted in universally poor performance, although there is a marked improvement when motifs are statistically significant against real background sequences. Moreover, on synthetic data where "ground truth" is known, discriminative performance of all algorithms is far below the theoretical upper bound, with pronounced "over-fitting" in training. A key conclusion from this work is that the failure of de novo discovery approaches to accurately identify motifs is basically due to statistical intractability resulting from the fixed size of co-regulated gene clusters, and thus such failures do not necessarily provide evidence that unfound motifs are not active biologically. Consequently, the use of prior knowledge to enhance motif discovery is not just advantageous but necessary. An implementation of the LR and ALR

  14. EXTREME: an online EM algorithm for motif discovery.

    Science.gov (United States)

    Quang, Daniel; Xie, Xiaohui

    2014-06-15

    Identifying regulatory elements is a fundamental problem in the field of gene transcription. Motif discovery-the task of identifying the sequence preference of transcription factor proteins, which bind to these elements-is an important step in this challenge. MEME is a popular motif discovery algorithm. Unfortunately, MEME's running time scales poorly with the size of the dataset. Experiments such as ChIP-Seq and DNase-Seq are providing a rich amount of information on the binding preference of transcription factors. MEME cannot discover motifs in data from these experiments in a practical amount of time without a compromising strategy such as discarding a majority of the sequences. We present EXTREME, a motif discovery algorithm designed to find DNA-binding motifs in ChIP-Seq and DNase-Seq data. Unlike MEME, which uses the expectation-maximization algorithm for motif discovery, EXTREME uses the online expectation-maximization algorithm to discover motifs. EXTREME can discover motifs in large datasets in a practical amount of time without discarding any sequences. Using EXTREME on ChIP-Seq and DNase-Seq data, we discover many motifs, including some novel and infrequent motifs that can only be discovered by using the entire dataset. Conservation analysis of one of these novel infrequent motifs confirms that it is evolutionarily conserved and possibly functional. All source code is available at the Github repository http://github.com/uci-cbcl/EXTREME. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  15. The limits of de novo DNA motif discovery.

    Directory of Open Access Journals (Sweden)

    David Simcha

    Full Text Available A major challenge in molecular biology is reverse-engineering the cis-regulatory logic that plays a major role in the control of gene expression. This program includes searching through DNA sequences to identify "motifs" that serve as the binding sites for transcription factors or, more generally, are predictive of gene expression across cellular conditions. Several approaches have been proposed for de novo motif discovery-searching sequences without prior knowledge of binding sites or nucleotide patterns. However, unbiased validation is not straightforward. We consider two approaches to unbiased validation of discovered motifs: testing the statistical significance of a motif using a DNA "background" sequence model to represent the null hypothesis and measuring performance in predicting membership in gene clusters. We demonstrate that the background models typically used are "too null," resulting in overly optimistic assessments of significance, and argue that performance in predicting TF binding or expression patterns from DNA motifs should be assessed by held-out data, as in predictive learning. Applying this criterion to common motif discovery methods resulted in universally poor performance, although there is a marked improvement when motifs are statistically significant against real background sequences. Moreover, on synthetic data where "ground truth" is known, discriminative performance of all algorithms is far below the theoretical upper bound, with pronounced "over-fitting" in training. A key conclusion from this work is that the failure of de novo discovery approaches to accurately identify motifs is basically due to statistical intractability resulting from the fixed size of co-regulated gene clusters, and thus such failures do not necessarily provide evidence that unfound motifs are not active biologically. Consequently, the use of prior knowledge to enhance motif discovery is not just advantageous but necessary. An implementation of

  16. Assessing Local Structure Motifs Using Order Parameters for Motif Recognition, Interstitial Identification, and Diffusion Path Characterization

    Directory of Open Access Journals (Sweden)

    Nils E. R. Zimmermann

    2017-11-01

    Full Text Available Structure–property relationships form the basis of many design rules in materials science, including synthesizability and long-term stability of catalysts, control of electrical and optoelectronic behavior in semiconductors, as well as the capacity of and transport properties in cathode materials for rechargeable batteries. The immediate atomic environments (i.e., the first coordination shells of a few atomic sites are often a key factor in achieving a desired property. Some of the most frequently encountered coordination patterns are tetrahedra, octahedra, body and face-centered cubic as well as hexagonal close packed-like environments. Here, we showcase the usefulness of local order parameters to identify these basic structural motifs in inorganic solid materials by developing classification criteria. We introduce a systematic testing framework, the Einstein crystal test rig, that probes the response of order parameters to distortions in perfect motifs to validate our approach. Subsequently, we highlight three important application cases. First, we map basic crystal structure information of a large materials database in an intuitive manner by screening the Materials Project (MP database (61,422 compounds for element-specific motif distributions. Second, we use the structure-motif recognition capabilities to automatically find interstitials in metals, semiconductor, and insulator materials. Our Interstitialcy Finding Tool (InFiT facilitates high-throughput screenings of defect properties. Third, the order parameters are reliable and compact quantitative structure descriptors for characterizing diffusion hops of intercalants as our example of magnesium in MnO2-spinel indicates. Finally, the tools developed in our work are readily and freely available as software implementations in the pymatgen library, and we expect them to be further applied to machine-learning approaches for emerging applications in materials science.

  17. Functional diversity of CTCFs is encoded in their binding motifs.

    Science.gov (United States)

    Fang, Rongxin; Wang, Chengqi; Skogerbo, Geir; Zhang, Zhihua

    2015-08-28

    The CCCTC-binding factor (CTCF) has diverse regulatory functions. However, the definitive characteristics of the CTCF binding motif required for its functional diversity still remains elusive. Here, we describe a new motif discovery workflow by which we have identified three CTCF binding motif variations with highly divergent functionalities. Supported by transcriptomic, epigenomic and chromatin-interactomic data, we show that the functional diversity of the CTCF binding motifs is strongly associated with their GC content, CpG dinucleotide coverage and relative DNA methylation level at the 12th position of the motifs. Further analysis suggested that the co-localization of cohesin, the key factor in cohesion of sister chromatids, is negatively correlated with the CpG coverage and the relative DNA methylation level at the 12th position. Finally, we present evidences for a hypothetical model in which chromatin interactions between promoters and distal regulatory regions are likely mediated by CTCFs binding to sequences with high CpG. These results demonstrate the existence of definitive CTCF binding motifs corresponding to CTCF's diverse functions, and that the functional diversity of the motifs is strongly associated with genetic and epigenetic features at the 12th position of the motifs.

  18. Identifying novel sequence variants of RNA 3D motifs

    Science.gov (United States)

    Zirbel, Craig L.; Roll, James; Sweeney, Blake A.; Petrov, Anton I.; Pirrung, Meg; Leontis, Neocles B.

    2015-01-01

    Predicting RNA 3D structure from sequence is a major challenge in biophysics. An important sub-goal is accurately identifying recurrent 3D motifs from RNA internal and hairpin loop sequences extracted from secondary structure (2D) diagrams. We have developed and validated new probabilistic models for 3D motif sequences based on hybrid Stochastic Context-Free Grammars and Markov Random Fields (SCFG/MRF). The SCFG/MRF models are constructed using atomic-resolution RNA 3D structures. To parameterize each model, we use all instances of each motif found in the RNA 3D Motif Atlas and annotations of pairwise nucleotide interactions generated by the FR3D software. Isostericity relations between non-Watson–Crick basepairs are used in scoring sequence variants. SCFG techniques model nested pairs and insertions, while MRF ideas handle crossing interactions and base triples. We use test sets of randomly-generated sequences to set acceptance and rejection thresholds for each motif group and thus control the false positive rate. Validation was carried out by comparing results for four motif groups to RMDetect. The software developed for sequence scoring (JAR3D) is structured to automatically incorporate new motifs as they accumulate in the RNA 3D Motif Atlas when new structures are solved and is available free for download. PMID:26130723

  19. The effect of orthology and coregulation on detecting regulatory motifs.

    Directory of Open Access Journals (Sweden)

    Valerie Storms

    Full Text Available BACKGROUND: Computational de novo discovery of transcription factor binding sites is still a challenging problem. The growing number of sequenced genomes allows integrating orthology evidence with coregulation information when searching for motifs. Moreover, the more advanced motif detection algorithms explicitly model the phylogenetic relatedness between the orthologous input sequences and thus should be well adapted towards using orthologous information. In this study, we evaluated the conditions under which complementing coregulation with orthologous information improves motif detection for the class of probabilistic motif detection algorithms with an explicit evolutionary model. METHODOLOGY: We designed datasets (real and synthetic covering different degrees of coregulation and orthologous information to test how well Phylogibbs and Phylogenetic sampler, as representatives of the motif detection algorithms with evolutionary model performed as compared to MEME, a more classical motif detection algorithm that treats orthologs independently. RESULTS AND CONCLUSIONS: Under certain conditions detecting motifs in the combined coregulation-orthology space is indeed more efficient than using each space separately, but this is not always the case. Moreover, the difference in success rate between the advanced algorithms and MEME is still marginal. The success rate of motif detection depends on the complex interplay between the added information and the specificities of the applied algorithms. Insights in this relation provide information useful to both developers and users. All benchmark datasets are available at http://homes.esat.kuleuven.be/~kmarchal/Supplementary_Storms_Valerie_PlosONE.

  20. Fingerprint motifs of phytases | Fan | African Journal of Biotechnology

    African Journals Online (AJOL)

    Among the total of potential 173 phytases gained in 11 plant genomes through MAST, PAPhys are the major phytases, and HAPhys are the minor, and other phytase groups are not found in planta. Keywords: Phytase, fingerprint motif, multiple EM for motif elicitation (MEME), MAST African Journal of Biotechnology Vol.

  1. Probing structural changes of self assembled i-motif DNA

    KAUST Repository

    Lee, Iljoon

    2015-01-01

    We report an i-motif structural probing system based on Thioflavin T (ThT) as a fluorescent sensor. This probe can discriminate the structural changes of RET and Rb i-motif sequences according to pH change. This journal is

  2. ELM: the status of the 2010 eukaryotic linear motif resource.

    Science.gov (United States)

    Gould, Cathryn M; Diella, Francesca; Via, Allegra; Puntervoll, Pål; Gemünd, Christine; Chabanis-Davidson, Sophie; Michael, Sushama; Sayadi, Ahmed; Bryne, Jan Christian; Chica, Claudia; Seiler, Markus; Davey, Norman E; Haslam, Niall; Weatheritt, Robert J; Budd, Aidan; Hughes, Tim; Pas, Jakub; Rychlewski, Leszek; Travé, Gilles; Aasland, Rein; Helmer-Citterich, Manuela; Linding, Rune; Gibson, Toby J

    2010-01-01

    Linear motifs are short segments of multidomain proteins that provide regulatory functions independently of protein tertiary structure. Much of intracellular signalling passes through protein modifications at linear motifs. Many thousands of linear motif instances, most notably phosphorylation sites, have now been reported. Although clearly very abundant, linear motifs are difficult to predict de novo in protein sequences due to the difficulty of obtaining robust statistical assessments. The ELM resource at http://elm.eu.org/ provides an expanding knowledge base, currently covering 146 known motifs, with annotation that includes >1300 experimentally reported instances. ELM is also an exploratory tool for suggesting new candidates of known linear motifs in proteins of interest. Information about protein domains, protein structure and native disorder, cellular and taxonomic contexts is used to reduce or deprecate false positive matches. Results are graphically displayed in a 'Bar Code' format, which also displays known instances from homologous proteins through a novel 'Instance Mapper' protocol based on PHI-BLAST. ELM server output provides links to the ELM annotation as well as to a number of remote resources. Using the links, researchers can explore the motifs, proteins, complex structures and associated literature to evaluate whether candidate motifs might be worth experimental investigation.

  3. Aztec, Incan and Mayan Motifs...Lead to Distinctive Designs.

    Science.gov (United States)

    Shields, Joanne

    2001-01-01

    Describes an art project for seventh-grade students in which they choose motifs based on Incan, Aztec, and Mayan Indian materials to incorporate into two-dimensional designs. Explains that the activity objective is to create a unified, balanced and pleasing composition using a minimum of three motifs. (CMK)

  4. BlockLogo: Visualization of peptide and sequence motif conservation

    DEFF Research Database (Denmark)

    Olsen, Lars Rønn; Kudahl, Ulrich Johan; Simon, Christian

    2013-01-01

    , selection of motif positions, type of sequence, and output format definition. The output has BlockLogo along with the sequence logo, and a table of motif frequencies. We deployed BlockLogo as an online application and have demonstrated its utility through examples that show visualization of T-cell epitopes...

  5. Discovering large network motifs from a complex biological network

    Science.gov (United States)

    Terada, Aika; Sese, Jun

    2009-12-01

    Graph structures representing relationships between entries have been studied in statistical analysis, and the results of these studies have been applied to biological networks, whose nodes and edges represent proteins and the relationships between them, respectively. Most of the studies have focused on only graph structures such as scale-free properties and cliques, but the relationships between nodes are also important features since most of the proteins perform their functions by connecting to other proteins. In order to determine such relationships, the problem of network motif discovery has been addressed; network motifs are frequently appearing graph structures in a given graph. However, the methods for network motif discovery are highly restrictive for the application to biological network because they can only be used to find small network motifs or they do not consider noise and uncertainty in observations. In this study, we introduce a new index to measure network motifs called AR index and develop a novel algorithm called ARIANA for finding large motifs even when the network has noise. Experiments using a synthetic network verify that our method can find better network motifs than an existing algorithm. By applying ARIANA to a real complex biological network, we find network motifs associated with regulations of start time of cell functions and generation of cell energies and discover that the cell cycle proteins can be categorized into two different groups.

  6. Stochastic EM-based TFBS motif discovery with MITSU.

    Science.gov (United States)

    Kilpatrick, Alastair M; Ward, Bruce; Aitken, Stuart

    2014-06-15

    The Expectation-Maximization (EM) algorithm has been successfully applied to the problem of transcription factor binding site (TFBS) motif discovery and underlies the most widely used motif discovery algorithms. In the wider field of probabilistic modelling, the stochastic EM (sEM) algorithm has been used to overcome some of the limitations of the EM algorithm; however, the application of sEM to motif discovery has not been fully explored. We present MITSU (Motif discovery by ITerative Sampling and Updating), a novel algorithm for motif discovery, which combines sEM with an improved approximation to the likelihood function, which is unconstrained with regard to the distribution of motif occurrences within the input dataset. The algorithm is evaluated quantitatively on realistic synthetic data and several collections of characterized prokaryotic TFBS motifs and shown to outperform EM and an alternative sEM-based algorithm, particularly in terms of site-level positive predictive value. Java executable available for download at http://www.sourceforge.net/p/mitsu-motif/, supported on Linux/OS X. © The Author 2014. Published by Oxford University Press.

  7. Unmasking functional motifs within disordered regions of proteins.

    Science.gov (United States)

    Das, Rahul K; Mao, Albert H; Pappu, Rohit V

    2012-04-17

    Eukaryotic proteins often possess long stretches that fail to adopt well-defined, three-dimensional structures. These intrinsically disordered regions are associated with cell signaling through the enrichment of hub proteins of networks and as targets for posttranslational modifications. Although disordered regions are readily identified because of their distinct sequence characteristics, it is difficult to predict the functions associated with these regions. This is because disordered regions often house short (two- to five-residue) linear motifs that mediate intermolecular interactions. Predicting their function requires the ability to identify the functionally relevant motifs. If one assumes that functional motifs are highly conserved as compared to background sequence contexts, then a suitable comparative genomics approach proves to be powerful in unmasking functional motifs that are part of disordered regions. This approach has successfully identified known functional motifs and predicted a set of new motifs that might yield important insights regarding previously unknown functionalities for disordered regions. Given knowledge of highly conserved motifs, one can assess whether the rapidly changing sequence contexts are actuators of the functionalities of short linear motifs within disordered regions. This should have important implications for engineering and targeting hub proteins in signaling networks.

  8. Ancient Writers’ Motifs in Spanish Golden Age Drama

    Directory of Open Access Journals (Sweden)

    Bojana Tomc

    2016-12-01

    Full Text Available In Spanish Golden Age drama we come across all forms of the reception of ancient writers’ motifs: explicit (direct quotation of an ancient author, where the quotation may be more or less complete, or a clear allusion to it, implicit (where there is no explicit mentioning of the ancient source, however certain ancient elements are mentioned such as persons, places, historical circumstances, hidden (where there is no clear hint about a literary intervention in Antiquity or an imitation of the literary excerpt or motif, as well as direct imitation (aemulatio or adaptation (variatio. In the Renaissance and Baroque there are almost no motifs, which could not be taken over from Antiquity without a transformation or innovation. If there is a close correspondence to the ancient motif, it is generally sufficient simply to mention it or employ a side motif as an illustration of a similar situation without elaborating the motif further or weaving it more deeply into the supporting fabric of the dramatic work. The ancient authors who contribute the motifs are numerous and diverse: Vergil, the Roman elegists Propertius in Tibullus, the lyric poet Horace, the comedian Plautus, the stoic philosopher Seneca, the historian Tacitus, the novelist Apuleius, as well as Greek dramatist Aeschylus and stoic philosopher Epictetus. The genres, which are a source for the surviving ancient motifs in the Golden Age in the selected authors, include literary as well as not-literary forms: epic poetry, lyric, dramatics, philosophy and historiography.

  9. Signatures de l'invisible

    CERN Multimedia

    CERN Press Office. Geneva

    2000-01-01

    "Signatures of the Invisible" is an unique collaboration between contemporary artists and contemporary physicists which has the potential to help redefine the relationship between science and art. "Signatures of the Invisible" is jointly organised by the London Institute - the world's largest college of art and design and CERN*, the world's leading particle physics laboratory. 12 leading visual artists:

  10. Ship Signature Management System : Functionality

    NARCIS (Netherlands)

    Arciszewski, H.F.R.; Lier, L. van; Meijer, Y.G.S.; Noordkamp, H.W.; Wassenaar, A.S.

    2010-01-01

    A signature of a platform is the manner in which the platform manifests itself to a certain type of sensor and how observable it is when such a sensor is used to detect the platform. Because many military platforms use sensors in different media, it is the total of its different signatures that

  11. MotifCombinator: a web-based tool to search for combinations of cis-regulatory motifs

    Directory of Open Access Journals (Sweden)

    Tsunoda Tatsuhiko

    2007-03-01

    Full Text Available Abstract Background A combination of multiple types of transcription factors and cis-regulatory elements is often required for gene expression in eukaryotes, and the combinatorial regulation confers specific gene expression to tissues or environments. To reveal the combinatorial regulation, computational methods are developed that efficiently infer combinations of cis-regulatory motifs that are important for gene expression as measured by DNA microarrays. One promising type of computational method is to utilize regression analysis between expression levels and scores of motifs in input sequences. This type takes full advantage of information on expression levels because it does not require that the expression level of each gene be dichotomized according to whether or not it reaches a certain threshold level. However, there is no web-based tool that employs regression methods to systematically search for motif combinations and that practically handles combinations of more than two or three motifs. Results We here introduced MotifCombinator, an online tool with a user-friendly interface, to systematically search for combinations composed of any number of motifs based on regression methods. The tool utilizes well-known regression methods (the multivariate linear regression, the multivariate adaptive regression spline or MARS, and the multivariate logistic regression method for this purpose, and uses the genetic algorithm to search for combinations composed of any desired number of motifs. The visualization systems in this tool help users to intuitively grasp the process of the combination search, and the backup system allows users to easily stop and restart calculations that are expected to require large computational time. This tool also provides preparatory steps needed for systematic combination search – i.e., selecting single motifs to constitute combinations and cutting out redundant similar motifs based on clustering analysis. Conclusion

  12. Classification and assessment tools for structural motif discovery algorithms.

    Science.gov (United States)

    Badr, Ghada; Al-Turaiki, Isra; Mathkour, Hassan

    2013-01-01

    Motif discovery is the problem of finding recurring patterns in biological data. Patterns can be sequential, mainly when discovered in DNA sequences. They can also be structural (e.g. when discovering RNA motifs). Finding common structural patterns helps to gain a better understanding of the mechanism of action (e.g. post-transcriptional regulation). Unlike DNA motifs, which are sequentially conserved, RNA motifs exhibit conservation in structure, which may be common even if the sequences are different. Over the past few years, hundreds of algorithms have been developed to solve the sequential motif discovery problem, while less work has been done for the structural case. In this paper, we survey, classify, and compare different algorithms that solve the structural motif discovery problem, where the underlying sequences may be different. We highlight their strengths and weaknesses. We start by proposing a benchmark dataset and a measurement tool that can be used to evaluate different motif discovery approaches. Then, we proceed by proposing our experimental setup. Finally, results are obtained using the proposed benchmark to compare available tools. To the best of our knowledge, this is the first attempt to compare tools solely designed for structural motif discovery. Results show that the accuracy of discovered motifs is relatively low. The results also suggest a complementary behavior among tools where some tools perform well on simple structures, while other tools are better for complex structures. We have classified and evaluated the performance of available structural motif discovery tools. In addition, we have proposed a benchmark dataset with tools that can be used to evaluate newly developed tools.

  13. Cell surface lectin array: parameters affecting cell glycan signature.

    Science.gov (United States)

    Landemarre, Ludovic; Cancellieri, Perrine; Duverger, Eric

    2013-04-01

    Among the "omics", glycomics is one of the most complex fields and needs complementary strategies of analysis to decipher the "glycan dictionary". As an alternative method, which has developed since the beginning of the 21st century, lectin array technology could generate relevant information related to glycan motifs, accessibility and a number of other valuable insights from molecules (purified and non-purified) or cells. Based on a cell line model, this study deals with the key parameters that influence the whole cell surface glycan interaction with lectin arrays and the consequences on the interpretation and reliability of the results. The comparison between the adherent and suspension forms of Chinese Hamster Ovary (CHO) cells, showed respective glycan signatures, which could be inhibited specifically by neoglycoproteins. The modifications of the respective glycan signatures were also revealed according to the detachment modes and cell growth conditions. Finally the power of lectin array technology was highlighted by the possibility of selecting and characterizing a specific clone from the mother cell line, based on the slight difference determination in the respective glycan signatures.

  14. A motif for infinite metal atom wires.

    Science.gov (United States)

    Yin, Xi; Warren, Steven A; Pan, Yung-Tin; Tsao, Kai-Chieh; Gray, Danielle L; Bertke, Jeffery; Yang, Hong

    2014-12-15

    A new motif for infinite metal atom wires with tunable compositions and properties is developed based on the connection between metal paddlewheel and square planar complex moieties. Two infinite Pd chain compounds, [Pd4(CO)4(OAc)4Pd(acac)2] 1 and [Pd4(CO)4(TFA)4Pd(acac)2] 2, and an infinite Pd-Pt heterometallic chain compound, [Pd4(CO)4(OAc)4Pt(acac)2] 3, are identified by single-crystal X-ray diffraction analysis. In these new structures, the paddlewheel moiety is a Pd four-membered ring coordinated by bridging carboxylic ligands and μ2 carbonyl ligands. The planar moiety is either Pd(acac)2 or Pt(acac)2 (acac = acetylacetonate). These moieties are connected by metallophilic interactions. The results showed that these one-dimensional metal wire compounds have photoluminescent properties that are tunable by changing ligands and metal ions. 3 can also serve as a single source precursor for making Pd4Pt bimetallic nanostructures with precise control of metal composition. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Tripartite motif 32 prevents pathological cardiac hypertrophy.

    Science.gov (United States)

    Chen, Lijuan; Huang, Jia; Ji, Yanxiao; Zhang, Xiaojing; Wang, Pixiao; Deng, Keqiong; Jiang, Xi; Ma, Genshan; Li, Hongliang

    2016-05-01

    TRIM32 (tripartite motif 32) is widely accepted to be an E3 ligase that interacts with and eventually ubiquitylates multiple substrates. TRIM32 mutants have been associated with LGMD-2H (limb girdle muscular dystrophy 2H). However, whether TRIM32 is involved in cardiac hypertrophy induced by biomechanical stresses and neurohumoral mediators remains unclear. We generated mice and isolated NRCMs (neonatal rat cardiomyocytes) that overexpressed or were deficient in TRIM32 to investigate the effect of TRIM32 on AB (aortic banding) or AngII (angiotensin II)-mediated cardiac hypertrophy. Echocardiography and both pathological and molecular analyses were used to determine the extent of cardiac hypertrophy and subsequent fibrosis. Our results showed that overexpression of TRIM32 in the heart significantly alleviated the hypertrophic response induced by pressure overload, whereas TRIM32 deficiency dramatically aggravated pathological cardiac remodelling. Similar results were also found in cultured NRCMs incubated with AngII. Mechanistically, the present study suggests that TRIM32 exerts cardioprotective action by interruption of Akt- but not MAPK (mitogen-dependent protein kinase)-dependent signalling pathways. Additionally, inactivation of Akt by LY294002 offset the exacerbated hypertrophic response induced by AB in TRIM32-deficient mice. In conclusion, the present study indicates that TRIM32 plays a protective role in AB-induced pathological cardiac remodelling by blocking Akt-dependent signalling. Therefore TRIM32 could be a novel therapeutic target for the prevention of cardiac hypertrophy and heart failure. © 2016 The Author(s).

  16. Single promoters as regulatory network motifs

    Science.gov (United States)

    Zopf, Christopher; Maheshri, Narendra

    2012-02-01

    At eukaryotic promoters, chromatin can influence the relationship between a gene's expression and transcription factor (TF) activity. This additional complexity might allow single promoters to exhibit dynamical behavior commonly attributed to regulatory motifs involving multiple genes. We investigate the role of promoter chromatin architecture in the kinetics of gene activation using a previously described set of promoter variants based on the phosphate-regulated PHO5 promoter in S. cerevisiae. Accurate quantitative measurement of transcription activation kinetics is facilitated by a controllable and observable TF input to a promoter of interest leading to an observable expression output in single cells. We find the particular architecture of these promoters can result in a significant delay in activation, filtering of noisy TF signals, and a memory of previous activation -- dynamical behaviors reminiscent of a feed-forward loop but only requiring a single promoter. We suggest this is a consequence of chromatin transactions at the promoter, likely passing through a long-lived ``primed'' state between its inactive and competent states. Finally, we show our experimental setup can be generalized as a ``gene oscilloscope'' to probe the kinetics of heterologous promoter architectures.

  17. On the signature of LINCOS

    Science.gov (United States)

    Ollongren, Alexander

    2010-12-01

    Suppose the international SETI effort yields the discovery of some signal of evidently non-natural origin. Could it contain linguistic information formulated in some kind of Lingua Cosmica? One way to get insight into this matter is to consider what specific (bio) linguistic signature( s) could be attached to a cosmic language for interstellar communication—designed by humans or an alien society having reached a level of intelligence (and technology) comparable to or surpassing ours. For this purpose, we consider in the present paper the logico-linguistic system LINCOS for ( A)CETI, developed during a number of years by the author in several papers and a monograph [1]. The system has a two-fold signature, which distinguishes it significantly from natural languages. In fact abstract and concrete signatures can be distinguished. That an abstract kind occurs is due to the manner in which abstractions of reality are represented in LINCOS-texts. They can take compound forms because the system is multi-expressive—partly due to the availability of inductive (recursive) entities. On the other hand, the concrete signature of LINCOS is related to the distribution of delimiters and predefined tokens in texts. Assigning measures to concrete signatures will be discussed elsewhere. The present contribution concentrates on the abstract signature of the language. At the same time, it is realized that an alien Lingua Cosmica might, but not necessarily needs to have this kind of signatures.

  18. Statistical clumped isotope signatures

    Science.gov (United States)

    Röckmann, T.; Popa, M. E.; Krol, M. C.; Hofmann, M. E. G.

    2016-01-01

    High precision measurements of molecules containing more than one heavy isotope may provide novel constraints on element cycles in nature. These so-called clumped isotope signatures are reported relative to the random (stochastic) distribution of heavy isotopes over all available isotopocules of a molecule, which is the conventional reference. When multiple indistinguishable atoms of the same element are present in a molecule, this reference is calculated from the bulk (≈average) isotopic composition of the involved atoms. We show here that this referencing convention leads to apparent negative clumped isotope anomalies (anti-clumping) when the indistinguishable atoms originate from isotopically different populations. Such statistical clumped isotope anomalies must occur in any system where two or more indistinguishable atoms of the same element, but with different isotopic composition, combine in a molecule. The size of the anti-clumping signal is closely related to the difference of the initial isotope ratios of the indistinguishable atoms that have combined. Therefore, a measured statistical clumped isotope anomaly, relative to an expected (e.g. thermodynamical) clumped isotope composition, may allow assessment of the heterogeneity of the isotopic pools of atoms that are the substrate for formation of molecules. PMID:27535168

  19. Identifying topological motif patterns of human brain functional networks.

    Science.gov (United States)

    Wei, Yongbin; Liao, Xuhong; Yan, Chaogan; He, Yong; Xia, Mingrui

    2017-05-01

    Recent imaging connectome studies demonstrated that the human functional brain network follows an efficient small-world topology with cohesive functional modules and highly connected hubs. However, the functional motif patterns that represent the underlying information flow remain largely unknown. Here, we investigated motif patterns within directed human functional brain networks, which were derived from resting-state functional magnetic resonance imaging data with controlled confounding hemodynamic latencies. We found several significantly recurring motifs within the network, including the two-node reciprocal motif and five classes of three-node motifs. These recurring motifs were distributed in distinct patterns to support intra- and inter-module functional connectivity, which also promoted integration and segregation in network organization. Moreover, the significant participation of several functional hubs in the recurring motifs exhibited their critical role in global integration. Collectively, our findings highlight the basic architecture governing brain network organization and provide insight into the information flow mechanism underlying intrinsic brain activities. Hum Brain Mapp 38:2734-2750, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  20. i-Motif DNA: structure, stability and targeting with ligands.

    Science.gov (United States)

    Day, Henry A; Pavlou, Pavlos; Waller, Zoë A E

    2014-08-15

    i-Motifs are four-stranded DNA secondary structures which can form in sequences rich in cytosine. Stabilised by acidic conditions, they are comprised of two parallel-stranded DNA duplexes held together in an antiparallel orientation by intercalated, cytosine-cytosine(+) base pairs. By virtue of their pH dependent folding, i-motif forming DNA sequences have been used extensively as pH switches for applications in nanotechnology. Initially, i-motifs were thought to be unstable at physiological pH, which precluded substantial biological investigation. However, recent advances have shown that this is not always the case and that i-motif stability is highly dependent on factors such as sequence and environmental conditions. In this review, we discuss some of the different i-motif structures investigated to date and the factors which affect their topology, stability and dynamics. Ligands which can interact with these structures are necessary to aid investigations into the potential biological functions of i-motif DNA and herein we review the existing i-motif ligands and give our perspective on the associated challenges with targeting this structure. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Computational analyses of synergism in small molecular network motifs.

    Directory of Open Access Journals (Sweden)

    Yili Zhang

    2014-03-01

    Full Text Available Cellular functions and responses to stimuli are controlled by complex regulatory networks that comprise a large diversity of molecular components and their interactions. However, achieving an intuitive understanding of the dynamical properties and responses to stimuli of these networks is hampered by their large scale and complexity. To address this issue, analyses of regulatory networks often focus on reduced models that depict distinct, reoccurring connectivity patterns referred to as motifs. Previous modeling studies have begun to characterize the dynamics of small motifs, and to describe ways in which variations in parameters affect their responses to stimuli. The present study investigates how variations in pairs of parameters affect responses in a series of ten common network motifs, identifying concurrent variations that act synergistically (or antagonistically to alter the responses of the motifs to stimuli. Synergism (or antagonism was quantified using degrees of nonlinear blending and additive synergism. Simulations identified concurrent variations that maximized synergism, and examined the ways in which it was affected by stimulus protocols and the architecture of a motif. Only a subset of architectures exhibited synergism following paired changes in parameters. The approach was then applied to a model describing interlocked feedback loops governing the synthesis of the CREB1 and CREB2 transcription factors. The effects of motifs on synergism for this biologically realistic model were consistent with those for the abstract models of single motifs. These results have implications for the rational design of combination drug therapies with the potential for synergistic interactions.

  2. Triadic motifs in the dependence networks of virtual societies

    Science.gov (United States)

    Xie, Wen-Jie; Li, Ming-Xia; Jiang, Zhi-Qiang; Zhou, Wei-Xing

    2014-06-01

    In friendship networks, individuals have different numbers of friends, and the closeness or intimacy between an individual and her friends is heterogeneous. Using a statistical filtering method to identify relationships about who depends on whom, we construct dependence networks (which are directed) from weighted friendship networks of avatars in more than two hundred virtual societies of a massively multiplayer online role-playing game (MMORPG). We investigate the evolution of triadic motifs in dependence networks. Several metrics show that the virtual societies evolved through a transient stage in the first two to three weeks and reached a relatively stable stage. We find that the unidirectional loop motif (M9) is underrepresented and does not appear, open motifs are also underrepresented, while other close motifs are overrepresented. We also find that, for most motifs, the overall level difference of the three avatars in the same motif is significantly lower than average, whereas the sum of ranks is only slightly larger than average. Our findings show that avatars' social status plays an important role in the formation of triadic motifs.

  3. EAR motif-mediated transcriptional repression in plants

    Science.gov (United States)

    Kagale, Sateesh

    2011-01-01

    Ethylene-responsive element binding factor-associated amphiphilic repression (EAR) motif-mediated transcriptional repression is emerging as one of the principal mechanisms of plant gene regulation. The EAR motif, defined by the consensus sequence patterns of either LxLxL or DLN xxP, is the most predominant form of transcriptional repression motif so far identified in plants. Additionally, this active repression motif is highly conserved in transcriptional regulators known to function as negative regulators in a broad range of developmental and physiological processes across evolutionarily diverse plant species. Recent discoveries of co-repressors interacting with EAR motifs, such as TO PLESS (TPL) and AtSA P18, have begun to unravel the mechanisms of EAR motif-mediated repression. The demonstration of genetic interaction between mutants of TPL and AtHDA 19, co-complex formation between TPL-related 1 (TPR1) and AtHDA 19, as well as direct physical interaction between AtSA P18 and AtHDA 19 support a model where EAR repressors, via recruitment of chromatin remodeling factors, facilitate epigenetic regulation of gene expression. Here, we discuss the biological significance of EAR -mediated gene regulation in the broader context of plant biology and present literature evidence in support of a model for EAR motif-mediated repression via the recruitment and action of chromatin modifiers. Additionally, we discuss the possible influences of phosphorylation and ubiquitination on the function and turnover of EAR repressors. PMID:20935498

  4. Triadic motifs in the dependence networks of virtual societies.

    Science.gov (United States)

    Xie, Wen-Jie; Li, Ming-Xia; Jiang, Zhi-Qiang; Zhou, Wei-Xing

    2014-06-10

    In friendship networks, individuals have different numbers of friends, and the closeness or intimacy between an individual and her friends is heterogeneous. Using a statistical filtering method to identify relationships about who depends on whom, we construct dependence networks (which are directed) from weighted friendship networks of avatars in more than two hundred virtual societies of a massively multiplayer online role-playing game (MMORPG). We investigate the evolution of triadic motifs in dependence networks. Several metrics show that the virtual societies evolved through a transient stage in the first two to three weeks and reached a relatively stable stage. We find that the unidirectional loop motif (M9) is underrepresented and does not appear, open motifs are also underrepresented, while other close motifs are overrepresented. We also find that, for most motifs, the overall level difference of the three avatars in the same motif is significantly lower than average, whereas the sum of ranks is only slightly larger than average. Our findings show that avatars' social status plays an important role in the formation of triadic motifs.

  5. Profile-based short linear protein motif discovery

    Directory of Open Access Journals (Sweden)

    Haslam Niall J

    2012-05-01

    Full Text Available Abstract Background Short linear protein motifs are attracting increasing attention as functionally independent sites, typically 3–10 amino acids in length that are enriched in disordered regions of proteins. Multiple methods have recently been proposed to discover over-represented motifs within a set of proteins based on simple regular expressions. Here, we extend these approaches to profile-based methods, which provide a richer motif representation. Results The profile motif discovery method MEME performed relatively poorly for motifs in disordered regions of proteins. However, when we applied evolutionary weighting to account for redundancy amongst homologous proteins, and masked out poorly conserved regions of disordered proteins, the performance of MEME is equivalent to that of regular expression methods. However, the two approaches returned different subsets within both a benchmark dataset, and a more realistic discovery dataset. Conclusions Profile-based motif discovery methods complement regular expression based methods. Whilst profile-based methods are computationally more intensive, they are likely to discover motifs currently overlooked by regular expression methods.

  6. A speedup technique for (l, d-motif finding algorithms

    Directory of Open Access Journals (Sweden)

    Dinh Hieu

    2011-03-01

    Full Text Available Abstract Background The discovery of patterns in DNA, RNA, and protein sequences has led to the solution of many vital biological problems. For instance, the identification of patterns in nucleic acid sequences has resulted in the determination of open reading frames, identification of promoter elements of genes, identification of intron/exon splicing sites, identification of SH RNAs, location of RNA degradation signals, identification of alternative splicing sites, etc. In protein sequences, patterns have proven to be extremely helpful in domain identification, location of protease cleavage sites, identification of signal peptides, protein interactions, determination of protein degradation elements, identification of protein trafficking elements, etc. Motifs are important patterns that are helpful in finding transcriptional regulatory elements, transcription factor binding sites, functional genomics, drug design, etc. As a result, numerous papers have been written to solve the motif search problem. Results Three versions of the motif search problem have been proposed in the literature: Simple Motif Search (SMS, (l, d-motif search (or Planted Motif Search (PMS, and Edit-distance-based Motif Search (EMS. In this paper we focus on PMS. Two kinds of algorithms can be found in the literature for solving the PMS problem: exact and approximate. An exact algorithm identifies the motifs always and an approximate algorithm may fail to identify some or all of the motifs. The exact version of PMS problem has been shown to be NP-hard. Exact algorithms proposed in the literature for PMS take time that is exponential in some of the underlying parameters. In this paper we propose a generic technique that can be used to speedup PMS algorithms. Conclusions We present a speedup technique that can be used on any PMS algorithm. We have tested our speedup technique on a number of algorithms. These experimental results show that our speedup technique is indeed very

  7. Discovering sequence motifs in quantitative and qualitative pepetide data

    DEFF Research Database (Denmark)

    Andreatta, Massimo

    where the three-dimensional aspect of the interaction is prevalent, protein-peptide interactions can normally be represented simply by a linear binding motif. Phage display and peptide microarray technologies allow generating large libraries of peptide sequences and the parallel detection of thousands...... molecules, two classes of HLA molecules with recognized importance in immune response but poorly characterized sequence motifs. The sequence logos of 5 HLADP and 6 HLA-DQ molecules provide a characterization of their binding motifs at an unprecedented level of detail. The third paper in this thesis deals...

  8. C-terminal motif prediction in eukaryotic proteomes using comparative genomics and statistical over-representation across protein families

    Directory of Open Access Journals (Sweden)

    Cutler Sean R

    2007-06-01

    Full Text Available Abstract Background The carboxy termini of proteins are a frequent site of activity for a variety of biologically important functions, ranging from post-translational modification to protein targeting. Several short peptide motifs involved in protein sorting roles and dependent upon their proximity to the C-terminus for proper function have already been characterized. As a limited number of such motifs have been identified, the potential exists for genome-wide statistical analysis and comparative genomics to reveal novel peptide signatures functioning in a C-terminal dependent manner. We have applied a novel methodology to the prediction of C-terminal-anchored peptide motifs involving a simple z-statistic and several techniques for improving the signal-to-noise ratio. Results We examined the statistical over-representation of position-specific C-terminal tripeptides in 7 eukaryotic proteomes. Sequence randomization models and simple-sequence masking were applied to the successful reduction of background noise. Similarly, as C-terminal homology among members of large protein families may artificially inflate tripeptide counts in an irrelevant and obfuscating manner, gene-family clustering was performed prior to the analysis in order to assess tripeptide over-representation across protein families as opposed to across all proteins. Finally, comparative genomics was used to identify tripeptides significantly occurring in multiple species. This approach has been able to predict, to our knowledge, all C-terminally anchored targeting motifs present in the literature. These include the PTS1 peroxisomal targeting signal (SKL*, the ER-retention signal (K/HDEL*, the ER-retrieval signal for membrane bound proteins (KKxx*, the prenylation signal (CC* and the CaaX box prenylation motif. In addition to a high statistical over-representation of these known motifs, a collection of significant tripeptides with a high propensity for biological function exists

  9. ROMANIAN FOLKLORE MOTIFS IN FASHION DESIGN

    Directory of Open Access Journals (Sweden)

    MOCENCO Alexandra

    2014-05-01

    Full Text Available The traditional Romanian costume such as the entire popular art (architecture, woodcarvins, pottery etc. was born and lasted in our country since ancient times. Closely related to human existence, the traditional costume reflected over the years as reflected nowadays, the mentality and artistic conception of the people. Today the traditional Romanian costume became an inspiration source to the wholesale fashion production industry designers, both Romanian and international. Although the contemporary designers are working in accordance with a vision, using a wide area of styles, methods and current technology, they usually return to traditional techniques and ethnic folklore motifs, which converts and resize them, integrating them in their contemporary space. Adrian Oianu is a very appreciated Romanian designer who launched two collections inspired by his native’s country traditional costumes: “Suflecata pan’ la brau” (“Turned up ‘til the belt” and “Bucurie” (“Joy”. Dorin Negrau had as inspiration for his “Lost” collection the traditional costume from the Bihor region. Yves Saint Laurent had a collection inspired by the Romanian traditional flax blouses called “La blouse roumaine”. The paper presents the traditional Romanian values throw fashion collections. The research activity will create innovative concepts to support the garment industry in order to develop their own brand and to bring the design activities in Romania at an international level. The research was conducted during the initial stage of a project, financed through national founds, consisting in a documentary study on ethnographic characteristics of the popular costume from different regions of the country.

  10. Password-based digital signatures

    OpenAIRE

    Sivagnanasuntharam, Sangeepan

    2013-01-01

    This thesis is about implementing a digital signature scheme proposed by associate professor Kristian Gjøsteen and Oystein Thuen.The thesis explains the implementation, the challenges met and a security assessment of the implementation.

  11. Intrusion detection using secure signatures

    Science.gov (United States)

    Nelson, Trent Darnel; Haile, Jedediah

    2014-09-30

    A method and device for intrusion detection using secure signatures comprising capturing network data. A search hash value, value employing at least one one-way function, is generated from the captured network data using a first hash function. The presence of a search hash value match in a secure signature table comprising search hash values and an encrypted rule is determined. After determining a search hash value match, a decryption key is generated from the captured network data using a second hash function, a hash function different form the first hash function. One or more of the encrypted rules of the secure signatures table having a hash value equal to the generated search hash value are then decrypted using the generated decryption key. The one or more decrypted secure signature rules are then processed for a match and one or more user notifications are deployed if a match is identified.

  12. Epigenetic Signatures of Cigarette Smoking

    National Research Council Canada - National Science Library

    Joehanes, Roby; Just, A.C; Marioni, Riccardo; Pilling, Luke; Reynolds, Lindsay; Mandaviya, P.R; Guan, Weihua; Xu, T; Elks, Cathy; Aslibekyan, S; Moreno-Macías, Hortensia; Smith, Jennifer A; Brody, Jennifer; Dhingra, R; Yousefi, Paul; Pankow, James; Kunze, S; Shah, S.H; McRae, Allan F; Lohman, Kurt; Sha, J; Absher, Devin; Ferrucci, Luigi; Zhao, W; Demerath, Ellen; Bressler, Jan; Grove, Megan; Huan, Tianxiao; Liu, Chunyu; Mendelson, M.M; Yao, Chen; Kiel, Douglas P; Peters, Annette; Wang-Sattler, Rui; Visscher, Peter; Wray, Naomi; Starr, John; Ding, J; Roiguez, C.J; Wareham, Nick; Irvin, M.R; Zhi, D; Barrdahl, Myrto; Vineis, Paolo; Ambatipudi, S; Uitterlinden, Ané; Hofman, Albert; Schwartz, J; Colicino, E; Hou, L; Vokonas, P.S; Hernandez, Dena; Singleton, Anew; Bandinelli, Stefania; Turner, Stephen; Ware, Erin B; Smith, A.K; Klengel, Torsten; Binder, Elisabeth B; Psaty, Bruce; Taylor, Kent; Gharib, Sina; Swenson, B.R; Liang, L; Demeo, Dawn L; O'Connor, George; Herceg, Zdenko; Ressler, K.J; Conneely, Karen N; Sotoodehnia, Nona; Kardia, S.L.R; Melzer, David; Baccarelli, Anea A; Meurs, Joyce; Romieu, Isabelle; Arnett, Donna; Ong, K.K; Liu, Yongmei; Waldenberger, Melanie; Deary, Ian J; Fornage, Myriam; Levy, Daniel; London, Stephanie J

    2016-01-01

    textabstractBackground-DNA methylation leaves a long-term signature of smoking exposure and is one potential mechanism by which tobacco exposure predisposes to adverse health outcomes, such as cancers...

  13. Initial Semantics for Strengthened Signatures

    Directory of Open Access Journals (Sweden)

    André Hirschowitz

    2012-02-01

    Full Text Available We give a new general definition of arity, yielding the companion notions of signature and associated syntax. This setting is modular in the sense requested by Ghani and Uustalu: merging two extensions of syntax corresponds to building an amalgamated sum. These signatures are too general in the sense that we are not able to prove the existence of an associated syntax in this general context. So we have to select arities and signatures for which there exists the desired initial monad. For this, we follow a track opened by Matthes and Uustalu: we introduce a notion of strengthened arity and prove that the corresponding signatures have initial semantics (i.e. associated syntax. Our strengthened arities admit colimits, which allows the treatment of the λ-calculus with explicit substitution.

  14. Conformational flexibility may explain multiple cellular roles of PEST motifs.

    Science.gov (United States)

    Sandhu, Kuljeet Singh; Dash, Debasis

    2006-06-01

    PEST sequences are one of the major motifs that serve as signal for the protein degradation and are also involved in various cellular processes such as phosphorylation and protein-protein interaction. In our earlier study, we found that these motifs contribute largely to eukaryotic protein disorder. This observation led us to evaluate their conformational variability in the nonredundant Protein Data Bank (PDB) structures. For this purpose, crystallographic temperature factors, structural alignment of multiple NMR models, and dihedral angle order parameters have been used in this study. The study has revealed the hypermobility of PEST motifs as compared to other regions of the protein. Conformational flexibility may allow them to participate in number of molecular interactions under different conditions. This analysis may explain the role of protein backbone flexibility in bringing about multiple cellular roles of PEST motifs. 2006 Wiley-Liss, Inc.

  15. DNA regulatory motif selection based on support vector machine ...

    African Journals Online (AJOL)

    Administrator

    2011-10-19

    Oct 19, 2011 ... Conserved DNA sequences are essential to investigate the regulation and expression of nearby genes. .... where, i is the genes index, k is the total number of motif type in ..... environmental degradation or food, which causes.

  16. Limitations and potentials of current motif discovery algorithms

    National Research Council Canada - National Science Library

    Hu, Jianjun; Li, Bin; Kihara, Daisuke

    2005-01-01

    .... Here, we designed a comprehensive set of performance measures and benchmarked five modern sequence-based motif discovery algorithms using large datasets generated from Escherichia coli RegulonDB...

  17. An Entropy-Based Position Projection Algorithm for Motif Discovery.

    Science.gov (United States)

    Zhang, Yipu; Wang, Ping; Yan, Maode

    2016-01-01

    Motif discovery problem is crucial for understanding the structure and function of gene expression. Over the past decades, many attempts using consensus and probability training model for motif finding are successful. However, the most existing motif discovery algorithms are still time-consuming or easily trapped in a local optimum. To overcome these shortcomings, in this paper, we propose an entropy-based position projection algorithm, called EPP, which designs a projection process to divide the dataset and explores the best local optimal solution. The experimental results on real DNA sequences, Tompa data, and ChIP-seq data show that EPP is advantageous in dealing with the motif discovery problem and outperforms current widely used algorithms.

  18. An Entropy-Based Position Projection Algorithm for Motif Discovery

    Directory of Open Access Journals (Sweden)

    Yipu Zhang

    2016-01-01

    Full Text Available Motif discovery problem is crucial for understanding the structure and function of gene expression. Over the past decades, many attempts using consensus and probability training model for motif finding are successful. However, the most existing motif discovery algorithms are still time-consuming or easily trapped in a local optimum. To overcome these shortcomings, in this paper, we propose an entropy-based position projection algorithm, called EPP, which designs a projection process to divide the dataset and explores the best local optimal solution. The experimental results on real DNA sequences, Tompa data, and ChIP-seq data show that EPP is advantageous in dealing with the motif discovery problem and outperforms current widely used algorithms.

  19. POWRS: Position-Sensitive Motif Discovery: e40373

    National Research Council Canada - National Science Library

    Ian W Davis; Christopher Benninger; Philip N Benfey; Tedd Elich

    2012-01-01

    .... Here we present a new algorithm "POWRS" (POsition-sensitive WoRd Set) for identifying regulatory sequence motifs, specifically developed to address two common shortcomings of existing algorithms...

  20. Direct vs 2-stage approaches to structured motif finding

    Directory of Open Access Journals (Sweden)

    Federico Maria

    2012-08-01

    Full Text Available Abstract Background The notion of DNA motif is a mathematical abstraction used to model regions of the DNA (known as Transcription Factor Binding Sites, or TFBSs that are bound by a given Transcription Factor to regulate gene expression or repression. In turn, DNA structured motifs are a mathematical counterpart that models sets of TFBSs that work in concert in the gene regulations processes of higher eukaryotic organisms. Typically, a structured motif is composed of an ordered set of isolated (or simple motifs, separated by a variable, but somewhat constrained number of “irrelevant” base-pairs. Discovering structured motifs in a set of DNA sequences is a computationally hard problem that has been addressed by a number of authors using either a direct approach, or via the preliminary identification and successive combination of simple motifs. Results We describe a computational tool, named SISMA, for the de-novo discovery of structured motifs in a set of DNA sequences. SISMA is an exact, enumerative algorithm, meaning that it finds all the motifs conforming to the specifications. It does so in two stages: first it discovers all the possible component simple motifs, then combines them in a way that respects the given constraints. We developed SISMA mainly with the aim of understanding the potential benefits of such a 2-stage approach w.r.t. direct methods. In fact, no 2-stage software was available for the general problem of structured motif discovery, but only a few tools that solved restricted versions of the problem. We evaluated SISMA against other published tools on a comprehensive benchmark made of both synthetic and real biological datasets. In a significant number of cases, SISMA outperformed the competitors, exhibiting a good performance also in most of the cases in which it was inferior. Conclusions A reflection on the results obtained lead us to conclude that a 2-stage approach can be implemented with many advantages over direct

  1. The origin of motif families in food webs

    OpenAIRE

    Klaise, Janis; Johnson, Samuel

    2017-01-01

    Food webs have been found to exhibit remarkable “motif profiles”, patterns in the relative prevalences of all possible three-species subgraphs, and this has been related to ecosystem properties such as stability and robustness. Analysing 46 food webs of various kinds, we find that most food webs fall into one of two distinct motif families. The separation between the families is well predicted by a global measure of hierarchical order in directed networks—trophic coherence. We find that troph...

  2. Linear motif atlas for phosphorylation-dependent signaling

    DEFF Research Database (Denmark)

    Miller, Martin Lee; Jensen, LJ; Diella, F

    2008-01-01

    bind to them remains a challenge. NetPhorest is an atlas of consensus sequence motifs that covers 179 kinases and 104 phosphorylation-dependent binding domains [Src homology 2 (SH2), phosphotyrosine binding (PTB), BRCA1 C-terminal (BRCT), WW, and 14-3-3]. The atlas reveals new aspects of signaling...... sequence models of linear motifs. The atlas is available as a community resource (http://netphorest.info)....

  3. No tradeoff between versatility and robustness in gene circuit motifs

    OpenAIRE

    Payne Joshua L.

    2016-01-01

    Circuit motifs are small directed subgraphs that appear in real world networks significantly more often than in randomized networks. In the Boolean model of gene circuits most motifs are realized by multiple circuit genotypes. Each of a motif’s constituent circuit genotypes may have one or more functions which are embodied in the expression patterns the circuit forms in response to specific initial conditions. Recent enumeration of a space of nearly 17 million three gene circuit genotypes rev...

  4. Attribute-Based Digital Signature System

    NARCIS (Netherlands)

    Ibraimi, L.; Asim, Muhammad; Petkovic, M.

    2011-01-01

    An attribute-based digital signature system comprises a signature generation unit (1) for signing a message (m) by generating a signature (s) based on a user secret key (SK) associated with a set of user attributes, wherein the signature generation unit (1) is arranged for combining the user secret

  5. Practical Certificateless Aggregate Signatures From Bilinear Maps

    NARCIS (Netherlands)

    Gong, Zheng; Long, Y.; Hong, X.; Chen, Kefei

    2010-01-01

    Aggregate signature is a digital signature with a striking property that anyone can aggregate n individual signatures on n different messages which are signed by n distinct signers, into a single compact signature to reduce computational and storage costs. In this work, two practical certificateless

  6. Efficient motif finding algorithms for large-alphabet inputs

    Directory of Open Access Journals (Sweden)

    Pavlovic Vladimir

    2010-10-01

    Full Text Available Abstract Background We consider the problem of identifying motifs, recurring or conserved patterns, in the biological sequence data sets. To solve this task, we present a new deterministic algorithm for finding patterns that are embedded as exact or inexact instances in all or most of the input strings. Results The proposed algorithm (1 improves search efficiency compared to existing algorithms, and (2 scales well with the size of alphabet. On a synthetic planted DNA motif finding problem our algorithm is over 10× more efficient than MITRA, PMSPrune, and RISOTTO for long motifs. Improvements are orders of magnitude higher in the same setting with large alphabets. On benchmark TF-binding site problems (FNP, CRP, LexA we observed reduction in running time of over 12×, with high detection accuracy. The algorithm was also successful in rapidly identifying protein motifs in Lipocalin, Zinc metallopeptidase, and supersecondary structure motifs for Cadherin and Immunoglobin families. Conclusions Our algorithm reduces computational complexity of the current motif finding algorithms and demonstrate strong running time improvements over existing exact algorithms, especially in important and difficult cases of large-alphabet sequences.

  7. Discovering Motifs in Biological Sequences Using the Micron Automata Processor.

    Science.gov (United States)

    Roy, Indranil; Aluru, Srinivas

    2016-01-01

    Finding approximately conserved sequences, called motifs, across multiple DNA or protein sequences is an important problem in computational biology. In this paper, we consider the (l, d) motif search problem of identifying one or more motifs of length l present in at least q of the n given sequences, with each occurrence differing from the motif in at most d substitutions. The problem is known to be NP-complete, and the largest solved instance reported to date is (26,11). We propose a novel algorithm for the (l,d) motif search problem using streaming execution over a large set of non-deterministic finite automata (NFA). This solution is designed to take advantage of the micron automata processor, a new technology close to deployment that can simultaneously execute multiple NFA in parallel. We demonstrate the capability for solving much larger instances of the (l, d) motif search problem using the resources available within a single automata processor board, by estimating run-times for problem instances (39,18) and (40,17). The paper serves as a useful guide to solving problems using this new accelerator technology.

  8. BEAM web server: A tool for structural RNA motif discovery.

    Science.gov (United States)

    Pietrosanto, Marco; Adinolfi, Marta; Casula, Riccardo; Ausiello, Gabriele; Ferrè, Fabrizio; Helmer-Citterich, Manuela

    2017-10-31

    RNA structural motif finding is a relevant problem that becomes computationally hard when working on high-throughput data (e.g. eCLIP, PAR-CLIP), often represented by thousands of RNA molecules. Currently, the BEAM server is the only web tool capable to handle tens of thousands of RNA in input with a motif discovery procedure that is only limited by the current secondary structure prediction accuracies. The recently developed method BEAM (BEAr Motifs finder) can analyze tens of thousands of RNA molecules and identify RNA secondary structure motifs associated to a measure of their statistical significance. BEAM is extremely fast thanks to the BEAR encoding that transforms each RNA secondary structure in a string of characters. BEAM also exploits the evolutionary knowledge contained in a substitution matrix of secondary structure elements, extracted from the RFAM database of families of homologous RNAs. The BEAM web server has been designed to streamline data pre-processing by automatically handling folding and encoding of RNA sequences, giving users a choice for the preferred folding program. The server provides an intuitive and informative results page with the list of secondary structure motifs identified, the logo of each motif, its significance, graphic representation and information about its position in the RNA molecules sharing it. The web server is freely available at http://beam.uniroma2.it/and it is implemented in NodeJS and Python with all major browsers supported. marco.pietrosanto@uniroma2.it.

  9. Simulating realistic predator signatures in quantitative fatty acid signature analysis

    Science.gov (United States)

    Bromaghin, Jeffrey F.

    2015-01-01

    Diet estimation is an important field within quantitative ecology, providing critical insights into many aspects of ecology and community dynamics. Quantitative fatty acid signature analysis (QFASA) is a prominent method of diet estimation, particularly for marine mammal and bird species. Investigators using QFASA commonly use computer simulation to evaluate statistical characteristics of diet estimators for the populations they study. Similar computer simulations have been used to explore and compare the performance of different variations of the original QFASA diet estimator. In both cases, computer simulations involve bootstrap sampling prey signature data to construct pseudo-predator signatures with known properties. However, bootstrap sample sizes have been selected arbitrarily and pseudo-predator signatures therefore may not have realistic properties. I develop an algorithm to objectively establish bootstrap sample sizes that generates pseudo-predator signatures with realistic properties, thereby enhancing the utility of computer simulation for assessing QFASA estimator performance. The algorithm also appears to be computationally efficient, resulting in bootstrap sample sizes that are smaller than those commonly used. I illustrate the algorithm with an example using data from Chukchi Sea polar bears (Ursus maritimus) and their marine mammal prey. The concepts underlying the approach may have value in other areas of quantitative ecology in which bootstrap samples are post-processed prior to their use.

  10. SIGNATURE: A workbench for gene expression signature analysis

    Directory of Open Access Journals (Sweden)

    Chang Jeffrey T

    2011-11-01

    Full Text Available Abstract Background The biological phenotype of a cell, such as a characteristic visual image or behavior, reflects activities derived from the expression of collections of genes. As such, an ability to measure the expression of these genes provides an opportunity to develop more precise and varied sets of phenotypes. However, to use this approach requires computational methods that are difficult to implement and apply, and thus there is a critical need for intelligent software tools that can reduce the technical burden of the analysis. Tools for gene expression analyses are unusually difficult to implement in a user-friendly way because their application requires a combination of biological data curation, statistical computational methods, and database expertise. Results We have developed SIGNATURE, a web-based resource that simplifies gene expression signature analysis by providing software, data, and protocols to perform the analysis successfully. This resource uses Bayesian methods for processing gene expression data coupled with a curated database of gene expression signatures, all carried out within a GenePattern web interface for easy use and access. Conclusions SIGNATURE is available for public use at http://genepattern.genome.duke.edu/signature/.

  11. Significance analysis of prognostic signatures.

    Directory of Open Access Journals (Sweden)

    Andrew H Beck

    Full Text Available A major goal in translational cancer research is to identify biological signatures driving cancer progression and metastasis. A common technique applied in genomics research is to cluster patients using gene expression data from a candidate prognostic gene set, and if the resulting clusters show statistically significant outcome stratification, to associate the gene set with prognosis, suggesting its biological and clinical importance. Recent work has questioned the validity of this approach by showing in several breast cancer data sets that "random" gene sets tend to cluster patients into prognostically variable subgroups. This work suggests that new rigorous statistical methods are needed to identify biologically informative prognostic gene sets. To address this problem, we developed Significance Analysis of Prognostic Signatures (SAPS which integrates standard prognostic tests with a new prognostic significance test based on stratifying patients into prognostic subtypes with random gene sets. SAPS ensures that a significant gene set is not only able to stratify patients into prognostically variable groups, but is also enriched for genes showing strong univariate associations with patient prognosis, and performs significantly better than random gene sets. We use SAPS to perform a large meta-analysis (the largest completed to date of prognostic pathways in breast and ovarian cancer and their molecular subtypes. Our analyses show that only a small subset of the gene sets found statistically significant using standard measures achieve significance by SAPS. We identify new prognostic signatures in breast and ovarian cancer and their corresponding molecular subtypes, and we show that prognostic signatures in ER negative breast cancer are more similar to prognostic signatures in ovarian cancer than to prognostic signatures in ER positive breast cancer. SAPS is a powerful new method for deriving robust prognostic biological signatures from clinically

  12. Signature molecular descriptor : advanced applications.

    Energy Technology Data Exchange (ETDEWEB)

    Visco, Donald Patrick, Jr. (Tennessee Technological University, Cookeville, TN)

    2010-04-01

    In this work we report on the development of the Signature Molecular Descriptor (or Signature) for use in the solution of inverse design problems as well as in highthroughput screening applications. The ultimate goal of using Signature is to identify novel and non-intuitive chemical structures with optimal predicted properties for a given application. We demonstrate this in three studies: green solvent design, glucocorticoid receptor ligand design and the design of inhibitors for Factor XIa. In many areas of engineering, compounds are designed and/or modified in incremental ways which rely upon heuristics or institutional knowledge. Often multiple experiments are performed and the optimal compound is identified in this brute-force fashion. Perhaps a traditional chemical scaffold is identified and movement of a substituent group around a ring constitutes the whole of the design process. Also notably, a chemical being evaluated in one area might demonstrate properties very attractive in another area and serendipity was the mechanism for solution. In contrast to such approaches, computer-aided molecular design (CAMD) looks to encompass both experimental and heuristic-based knowledge into a strategy that will design a molecule on a computer to meet a given target. Depending on the algorithm employed, the molecule which is designed might be quite novel (re: no CAS registration number) and/or non-intuitive relative to what is known about the problem at hand. While CAMD is a fairly recent strategy (dating to the early 1980s), it contains a variety of bottlenecks and limitations which have prevented the technique from garnering more attention in the academic, governmental and industrial institutions. A main reason for this is how the molecules are described in the computer. This step can control how models are developed for the properties of interest on a given problem as well as how to go from an output of the algorithm to an actual chemical structure. This report

  13. Molecular signatures in breast cancer.

    Science.gov (United States)

    Lal, Samir; McCart Reed, Amy E; de Luca, Xavier M; Simpson, Peter T

    2017-12-01

    The use of molecular signatures to add value to standard clinical and pathological parameters has impacted clinical practice in many cancer types, but perhaps most notably in the breast cancer field. This is, in part, due to the considerable complexity of the disease at the clinical, morphological and molecular levels. The adoption of molecular profiling of DNA, RNA and protein continues to reveal important differences in the intrinsic biology between molecular subtypes and has begun to impact the way patients are managed. Several bioinformatic tools have been developed using DNA or RNA-based signatures to stratify the disease into biologically and/or clinically meaningful subgroups. Here, we review the approaches that have been used to develop gene expression signatures into currently available diagnostic assays (e.g., OncotypeDX® and Mammaprint®), plus we describe the latest work on genome sequencing, the methodologies used in the discovery process of mutational signatures, and the potential of these signatures to impact the clinic. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Structural and functional studies of a phosphatidic acid-binding antifungal plant defensin MtDef4: Identification of an RGFRRR motif governing fungal cell entry

    Energy Technology Data Exchange (ETDEWEB)

    Sagaram, Uma S.; El-Mounadi, Kaoutar; Buchko, Garry W.; Berg, Howard R.; Kaur, Jagdeep; Pandurangi, Raghoottama; Smith, Thomas J.; Shah, Dilip

    2013-12-04

    A highly conserved plant defensin MtDef4 potently inhibits the growth of a filamentous fungus Fusarium graminearum. MtDef4 is internalized by cells of F. graminearum. To determine its mechanism of fungal cell entry and antifungal action, NMR solution structure of MtDef4 has been determined. The analysis of its structure has revealed a positively charged patch on the surface of the protein consisting of arginine residues in its γ-core signature, a major determinant of the antifungal activity of MtDef4. Here, we report functional analysis of the RGFRRR motif of the γ-core signature of MtDef4. The replacement of RGFRRR to AAAARR or to RGFRAA not only abolishes fungal cell entry but also results in loss of the antifungal activity of MtDef4. MtDef4 binds strongly to phosphatidic acid (PA), a precursor for the biosynthesis of membrane phospholipids and a signaling lipid known to recruit cytosolic proteins to membranes. Mutations of RGFRRR which abolish fungal cell entry of MtDef4 also impair its binding to PA. Our results suggest that RGFRRR motif is a translocation signal for entry of MtDef4 into fungal cells and that this positively charged motif likely mediates interaction of this defensin with PA as part of its antifungal action.

  15. Assessing the effects of symmetry on motif discovery and modeling.

    Directory of Open Access Journals (Sweden)

    Lala M Motlhabi

    Full Text Available BACKGROUND: Identifying the DNA binding sites for transcription factors is a key task in modeling the gene regulatory network of a cell. Predicting DNA binding sites computationally suffers from high false positives and false negatives due to various contributing factors, including the inaccurate models for transcription factor specificity. One source of inaccuracy in the specificity models is the assumption of asymmetry for symmetric models. METHODOLOGY/PRINCIPAL FINDINGS: Using simulation studies, so that the correct binding site model is known and various parameters of the process can be systematically controlled, we test different motif finding algorithms on both symmetric and asymmetric binding site data. We show that if the true binding site is asymmetric the results are unambiguous and the asymmetric model is clearly superior to the symmetric model. But if the true binding specificity is symmetric commonly used methods can infer, incorrectly, that the motif is asymmetric. The resulting inaccurate motifs lead to lower sensitivity and specificity than would the correct, symmetric models. We also show how the correct model can be obtained by the use of appropriate measures of statistical significance. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that the most commonly used motif-finding approaches usually model symmetric motifs incorrectly, which leads to higher than necessary false prediction errors. It also demonstrates how alternative motif-finding methods can correct the problem, providing more accurate motif models and reducing the errors. Furthermore, it provides criteria for determining whether a symmetric or asymmetric model is the most appropriate for any experimental dataset.

  16. Mechanisms of Zero-Lag Synchronization in Cortical Motifs

    Science.gov (United States)

    Gollo, Leonardo L.; Mirasso, Claudio; Sporns, Olaf; Breakspear, Michael

    2014-01-01

    Zero-lag synchronization between distant cortical areas has been observed in a diversity of experimental data sets and between many different regions of the brain. Several computational mechanisms have been proposed to account for such isochronous synchronization in the presence of long conduction delays: Of these, the phenomenon of “dynamical relaying” – a mechanism that relies on a specific network motif – has proven to be the most robust with respect to parameter mismatch and system noise. Surprisingly, despite a contrary belief in the community, the common driving motif is an unreliable means of establishing zero-lag synchrony. Although dynamical relaying has been validated in empirical and computational studies, the deeper dynamical mechanisms and comparison to dynamics on other motifs is lacking. By systematically comparing synchronization on a variety of small motifs, we establish that the presence of a single reciprocally connected pair – a “resonance pair” – plays a crucial role in disambiguating those motifs that foster zero-lag synchrony in the presence of conduction delays (such as dynamical relaying) from those that do not (such as the common driving triad). Remarkably, minor structural changes to the common driving motif that incorporate a reciprocal pair recover robust zero-lag synchrony. The findings are observed in computational models of spiking neurons, populations of spiking neurons and neural mass models, and arise whether the oscillatory systems are periodic, chaotic, noise-free or driven by stochastic inputs. The influence of the resonance pair is also robust to parameter mismatch and asymmetrical time delays amongst the elements of the motif. We call this manner of facilitating zero-lag synchrony resonance-induced synchronization, outline the conditions for its occurrence, and propose that it may be a general mechanism to promote zero-lag synchrony in the brain. PMID:24763382

  17. Signature Visualization of Software Binaries

    Energy Technology Data Exchange (ETDEWEB)

    Panas, T

    2008-07-01

    In this paper we present work on the visualization of software binaries. In particular, we utilize ROSE, an open source compiler infrastructure, to pre-process software binaries, and we apply a landscape metaphor to visualize the signature of each binary (malware). We define the signature of a binary as a metric-based layout of the functions contained in the binary. In our initial experiment, we visualize the signatures of a series of computer worms that all originate from the same line. These visualizations are useful for a number of reasons. First, the images reveal how the archetype has evolved over a series of versions of one worm. Second, one can see the distinct changes between version. This allows the viewer to form conclusions about the development cycle of a particular worm.

  18. Fitting a mixture model by expectation maximization to discover motifs in biopolymers

    Energy Technology Data Exchange (ETDEWEB)

    Bailey, T.L.; Elkan, C. [Univ. of California, La Jolla, CA (United States)

    1994-12-31

    The algorithm described in this paper discovers one or more motifs in a collection of DNA or protein sequences by using the technique of expectation maximization to fit a two-component finite mixture model to the set of sequences. Multiple motifs are found by fitting a mixture model to the data, probabilistically erasing the occurrences of the motif thus found, and repeating the process to find successive motifs. The algorithm requires only a set of unaligned sequences and a number specifying the width of the motifs as input. It returns a model of each motif and a threshold which together can be used as a Bayes-optimal classifier for searching for occurrences of the motif in other databases. The algorithm estimates how many times each motif occurs in each sequence in the dataset and outputs an alignment of the occurrences of the motif. The algorithm is capable of discovering several different motifs with differing numbers of occurrences in a single dataset.

  19. Discovering motifs in ranked lists of DNA sequences.

    Directory of Open Access Journals (Sweden)

    Eran Eden

    2007-03-01

    Full Text Available Computational methods for discovery of sequence elements that are enriched in a target set compared with a background set are fundamental in molecular biology research. One example is the discovery of transcription factor binding motifs that are inferred from ChIP-chip (chromatin immuno-precipitation on a microarray measurements. Several major challenges in sequence motif discovery still require consideration: (i the need for a principled approach to partitioning the data into target and background sets; (ii the lack of rigorous models and of an exact p-value for measuring motif enrichment; (iii the need for an appropriate framework for accounting for motif multiplicity; (iv the tendency, in many of the existing methods, to report presumably significant motifs even when applied to randomly generated data. In this paper we present a statistical framework for discovering enriched sequence elements in ranked lists that resolves these four issues. We demonstrate the implementation of this framework in a software application, termed DRIM (discovery of rank imbalanced motifs, which identifies sequence motifs in lists of ranked DNA sequences. We applied DRIM to ChIP-chip and CpG methylation data and obtained the following results. (i Identification of 50 novel putative transcription factor (TF binding sites in yeast ChIP-chip data. The biological function of some of them was further investigated to gain new insights on transcription regulation networks in yeast. For example, our discoveries enable the elucidation of the network of the TF ARO80. Another finding concerns a systematic TF binding enhancement to sequences containing CA repeats. (ii Discovery of novel motifs in human cancer CpG methylation data. Remarkably, most of these motifs are similar to DNA sequence elements bound by the Polycomb complex that promotes histone methylation. Our findings thus support a model in which histone methylation and CpG methylation are mechanistically linked

  20. cWINNOWER algorithm for finding fuzzy dna motifs

    Science.gov (United States)

    Liang, S.; Samanta, M. P.; Biegel, B. A.

    2004-01-01

    The cWINNOWER algorithm detects fuzzy motifs in DNA sequences rich in protein-binding signals. A signal is defined as any short nucleotide pattern having up to d mutations differing from a motif of length l. The algorithm finds such motifs if a clique consisting of a sufficiently large number of mutated copies of the motif (i.e., the signals) is present in the DNA sequence. The cWINNOWER algorithm substantially improves the sensitivity of the winnower method of Pevzner and Sze by imposing a consensus constraint, enabling it to detect much weaker signals. We studied the minimum detectable clique size qc as a function of sequence length N for random sequences. We found that qc increases linearly with N for a fast version of the algorithm based on counting three-member sub-cliques. Imposing consensus constraints reduces qc by a factor of three in this case, which makes the algorithm dramatically more sensitive. Our most sensitive algorithm, which counts four-member sub-cliques, needs a minimum of only 13 signals to detect motifs in a sequence of length N = 12,000 for (l, d) = (15, 4). Copyright Imperial College Press.

  1. BayesMD: flexible biological modeling for motif discovery.

    Science.gov (United States)

    Tang, Man-Hung Eric; Krogh, Anders; Winther, Ole

    2008-12-01

    We present BayesMD, a Bayesian Motif Discovery model with several new features. Three different types of biological a priori knowledge are built into the framework in a modular fashion. A mixture of Dirichlets is used as prior over nucleotide probabilities in binding sites. It is trained on transcription factor (TF) databases in order to extract the typical properties of TF binding sites. In a similar fashion we train organism-specific priors for the background sequences. Lastly, we use a prior over the position of binding sites. This prior represents information complementary to the motif and background priors coming from conservation, local sequence complexity, nucleosome occupancy, etc. and assumptions about the number of occurrences. The Bayesian inference is carried out using a combination of exact marginalization (multinomial parameters) and sampling (over the position of sites). Robust sampling results are achieved using the advanced sampling method parallel tempering. In a post-analysis step candidate motifs with high marginal probability are found by searching among those motifs that contain sites that occur frequently. Thereby, maximum a posteriori inference for the motifs is avoided and the marginal probabilities can be used directly to assess the significance of the findings. The framework is benchmarked against other methods on a number of real and artificial data sets. The accompanying prediction server, documentation, software, models and data are available from http://bayesmd.binf.ku.dk/.

  2. How pathogens use linear motifs to perturb host cell networks

    KAUST Repository

    Via, Allegra

    2015-01-01

    Molecular mimicry is one of the powerful stratagems that pathogens employ to colonise their hosts and take advantage of host cell functions to guarantee their replication and dissemination. In particular, several viruses have evolved the ability to interact with host cell components through protein short linear motifs (SLiMs) that mimic host SLiMs, thus facilitating their internalisation and the manipulation of a wide range of cellular networks. Here we present convincing evidence from the literature that motif mimicry also represents an effective, widespread hijacking strategy in prokaryotic and eukaryotic parasites. Further insights into host motif mimicry would be of great help in the elucidation of the molecular mechanisms behind host cell invasion and the development of anti-infective therapeutic strategies.

  3. Metal-Free Motifs for Solar Fuel Applications

    Science.gov (United States)

    Ilic, Stefan; Zoric, Marija R.; Kadel, Usha Pandey; Huang, Yunjing; Glusac, Ksenija D.

    2017-05-01

    Metal-free motifs, such as graphitic carbon nitride, conjugated polymers, and doped nanostructures, are emerging as a new class of Earth-abundant materials for solar fuel devices. Although these metal-free structures show great potential, detailed mechanistic understanding of their performance remains limited. Here, we review important experimental and theoretical findings relevant to the role of metal-free motifs as either photoelectrodes or electrocatalysts. First, the light-harvesting characteristics of metal-free photoelectrodes (band energetics, exciton binding energies, charge carrier mobilities and lifetimes) are discussed and contrasted with those in traditional inorganic semiconductors (such as Si). Second, the mechanistic insights into the electrocatalytic oxygen reduction and evolution reactions, hydrogen evolution reaction, and carbon dioxide reduction reaction by metal-free motifs are summarized, including experimental surface-sensitive spectroscopy findings, studies on small molecular models, and computational modeling of these chemical transformations.

  4. PMS6MC: A Multicore Algorithm for Motif Discovery.

    Science.gov (United States)

    Bandyopadhyay, Shibdas; Sahni, Sartaj; Rajasekaran, Sanguthevar

    2013-11-18

    We develop an efficient multicore algorithm, PMS6MC, for the (l, d)-motif discovery problem in which we are to find all strings of length l that appear in every string of a given set of strings with at most d mismatches. PMS6MC is based on PMS6, which is currently the fastest single-core algorithm for motif discovery in large instances. The speedup, relative to PMS6, attained by our multicore algorithm ranges from a high of 6.62 for the (17,6) challenging instances to a low of 2.75 for the (13,4) challenging instances on an Intel 6-core system. We estimate that PMS6MC is 2 to 4 times faster than other parallel algorithms for motif search on large instances.

  5. PMS6MC: A Multicore Algorithm for Motif Discovery

    Directory of Open Access Journals (Sweden)

    Shibdas Bandyopadhyay

    2013-11-01

    Full Text Available We develop an efficient multicore algorithm, PMS6MC, for the (l; d-motif discovery problem in which we are to find all strings of length l that appear in every string of a given set of strings with at most d mismatches. PMS6MC is based on PMS6, which is currently the fastest single-core algorithm for motif discovery in large instances. The speedup, relative to PMS6, attained by our multicore algorithm ranges from a high of 6.62 for the (17,6 challenging instances to a low of 2.75 for the (13,4 challenging instances on an Intel 6-core system. We estimate that PMS6MC is 2 to 4 times faster than other parallel algorithms for motif search on large instances.

  6. Core signalling motif displaying multistability through multi-state enzymes

    DEFF Research Database (Denmark)

    Feng, Song; Saez Cornellana, Meritxell; Wiuf, Carsten Henrik

    2016-01-01

    the existence of multiple steady states. These conditions foster the intuition that bistability arises as a consequence of competition between the two states of the kinase. Extending from this result, we find that increasing the number of kinase states linearly translates into an increase in the number....... Here, we show that a key motif found predominantly in eukaryotic signalling systems, namely a futile signalling cycle, can display bistability when featuring a two-state kinase. We provide necessary and sufficient mathematical conditions on the kinetic parameters of this motif that guarantee...... of steady states in the system. These findings reveal, to our knowledge, a new mechanism for the generation of bistability and multistability in cellular signalling systems. Further the futile cycle featuring a two-state kinase is among the smallest bistable signalling motifs. We show that multi-state...

  7. Galaxy interactions : The HI signature

    NARCIS (Netherlands)

    Sancisi, R; Barnes, JE; Sanders, DB

    1999-01-01

    HI observations are an excellent tool for investigating tidal interactions. Ongoing major and minor interactions which can lead to traumatic mergers or to accretion and the triggering of star formation, show distinct HI signatures. Interactions and mergers in the recent past can also be recognized

  8. Signature simulation of mixed materials

    Science.gov (United States)

    Carson, Tyler D.; Salvaggio, Carl

    2015-05-01

    Soil target signatures vary due to geometry, chemical composition, and scene radiometry. Although radiative transfer models and function-fit physical models may describe certain targets in limited depth, the ability to incorporate all three signature variables is difficult. This work describes a method to simulate the transient signatures of soil by first considering scene geometry synthetically created using 3D physics engines. Through the assignment of spectral data from the Nonconventional Exploitation Factors Data System (NEFDS), the synthetic scene is represented as a physical mixture of particles. Finally, first principles radiometry is modeled using the Digital Imaging and Remote Sensing Image Generation (DIRSIG) model. With DIRSIG, radiometric and sensing conditions were systematically manipulated to produce and record goniometric signatures. The implementation of this virtual goniometer allows users to examine how a target bidirectional reflectance distribution function (BRDF) will change with geometry, composition, and illumination direction. By using 3D computer graphics models, this process does not require geometric assumptions that are native to many radiative transfer models. It delivers a discrete method to circumnavigate the significant cost of time and treasure associated with hardware-based goniometric data collections.

  9. Epigenetic Signatures of Cigarette Smoking

    NARCIS (Netherlands)

    R. Joehanes (Roby); Just, A.C. (Allan C.); R.E. Marioni (Riccardo); L.C. Pilling (Luke); L.M. Reynolds (Lindsay); Mandaviya, P.R. (Pooja R.); W. Guan (Weihua); Xu, T. (Tao); C.E. Elks (Cathy); Aslibekyan, S. (Stella); H. Moreno-Macías (Hortensia); J.A. Smith (Jennifer A); J. Brody (Jennifer); Dhingra, R. (Radhika); P. Yousefi (Paul); J.S. Pankow (James); Kunze, S. (Sonja); Shah, S.H. (Sonia H.); A.F. McRae (Allan F.); K. Lohman (Kurt); Sha, J. (Jin); D. Absher (Devin); L. Ferrucci (Luigi); Zhao, W. (Wei); E.W. Demerath (Ellen); J. Bressler (Jan); M.L. Grove (Megan); T. Huan (Tianxiao); C. Liu (Chunyu); Mendelson, M.M. (Michael M.); C. Yao (Chen); D.P. Kiel (Douglas P.); A. Peters (Annette); R. Wang-Sattler (Rui); P.M. Visscher (Peter); N.R. Wray (Naomi); J.M. Starr (John); Ding, J. (Jingzhong); Rodriguez, C.J. (Carlos J.); N.J. Wareham (Nick); Irvin, M.R. (Marguerite R.); Zhi, D. (Degui); M. Barrdahl (Myrto); P. Vineis (Paolo); Ambatipudi, S. (Srikant); A.G. Uitterlinden (André); A. Hofman (Albert); Schwartz, J. (Joel); Colicino, E. (Elena); Hou, L. (Lifang); Vokonas, P.S. (Pantel S.); D.G. Hernandez (Dena); A. Singleton (Andrew); S. Bandinelli (Stefania); S.T. Turner (Stephen); E.B. Ware (Erin B.); Smith, A.K. (Alicia K.); T. Klengel (Torsten); E.B. Binder (Elisabeth B.); B.M. Psaty (Bruce); K.D. Taylor (Kent); S.A. Gharib (Sina); Swenson, B.R. (Brenton R.); Liang, L. (Liming); D.L. Demeo (Dawn L.); G.T. O'Connor (George); Z. Herceg (Zdenko); Ressler, K.J. (Kerry J.); K.N. Conneely (Karen N.); N. Sotoodehnia (Nona); Kardia, S.L.R. (Sharon L. R.); D. Melzer (David); A.A. Baccarelli (Andrea A.); J.B.J. van Meurs (Joyce); I. Romieu (Isabelle); D.K. Arnett (Donna); Ong, K.K. (Ken K.); Y. Liu (Yongmei); M. Waldenberger (Melanie); I.J. Deary (Ian J.); M. Fornage (Myriam); D. Levy (Daniel); S.J. London (Stephanie J.)

    2016-01-01

    textabstractBackground-DNA methylation leaves a long-term signature of smoking exposure and is one potential mechanism by which tobacco exposure predisposes to adverse health outcomes, such as cancers, osteoporosis, lung, and cardiovascular disorders. Methods and Results-To comprehensively determine

  10. Disaster relief through composite signatures

    Science.gov (United States)

    Hawley, Chadwick T.; Hyde, Brian; Carpenter, Tom; Nichols, Steve

    2012-06-01

    A composite signature is a group of signatures that are related in such a way to more completely or further define a target or operational endeavor at a higher fidelity. This paper builds on previous work developing innovative composite signatures associated with civil disasters, including physical, chemical and pattern/behavioral. For the composite signature approach to be successful it requires effective data fusion and visualization. This plays a key role in both preparedness and the response and recovery which are critical to saving lives. Visualization tools enhance the overall understanding of the crisis by pulling together and analyzing the data, and providing a clear and complete analysis of the information to the organizations/agencies dependant on it for a successful operation. An example of this, Freedom Web, is an easy-to-use data visualization and collaboration solution for use in homeland security, emergency preparedness, situational awareness, and event management. The solution provides a nationwide common operating picture for all levels of government through a web based, map interface. The tool was designed to be utilized by non-geospatial experts and is easily tailored to the specific needs of the users. Consisting of standard COTS and open source databases and a web server, users can view, edit, share, and highlight information easily and quickly through a standard internet browser.

  11. Selection against spurious promoter motifs correlates withtranslational efficiency across bacteria

    Energy Technology Data Exchange (ETDEWEB)

    Froula, Jeffrey L.; Francino, M. Pilar

    2007-05-01

    Because binding of RNAP to misplaced sites could compromise the efficiency of transcription, natural selection for the optimization of gene expression should regulate the distribution of DNA motifs capable of RNAP-binding across the genome. Here we analyze the distribution of the -10 promoter motifs that bind the {sigma}{sup 70} subunit of RNAP in 42 bacterial genomes. We show that selection on these motifs operates across the genome, maintaining an over-representation of -10 motifs in regulatory sequences while eliminating them from the nonfunctional and, in most cases, from the protein coding regions. In some genomes, however, -10 sites are over-represented in the coding sequences; these sites could induce pauses effecting regulatory roles throughout the length of a transcriptional unit. For nonfunctional sequences, the extent of motif under-representation varies across genomes in a manner that broadly correlates with the number of tRNA genes, a good indicator of translational speed and growth rate. This suggests that minimizing the time invested in gene transcription is an important selective pressure against spurious binding. However, selection against spurious binding is detectable in the reduced genomes of host-restricted bacteria that grow at slow rates, indicating that components of efficiency other than speed may also be important. Minimizing the number of RNAP molecules per cell required for transcription, and the corresponding energetic expense, may be most relevant in slow growers. These results indicate that genome-level properties affecting the efficiency of transcription and translation can respond in an integrated manner to optimize gene expression. The detection of selection against promoter motifs in nonfunctional regions also implies that no sequence may evolve free of selective constraints, at least in the relatively small and unstructured genomes of bacteria.

  12. Genome Analysis of Conserved Dehydrin Motifs in Vascular Plants

    Directory of Open Access Journals (Sweden)

    Ahmad A. Malik

    2017-05-01

    Full Text Available Dehydrins, a large family of abiotic stress proteins, are defined by the presence of a mostly conserved motif known as the K-segment, and may also contain two other conserved motifs known as the Y-segment and S-segment. Using the dehydrin literature, we developed a sequence motif definition of the K-segment, which we used to create a large dataset of dehydrin sequences by searching the Pfam00257 dehydrin dataset and the Phytozome 10 sequences of vascular plants. A comprehensive analysis of these sequences reveals that lysine residues are highly conserved in the K-segment, while the amino acid type is often conserved at other positions. Despite the Y-segment name, the central tyrosine is somewhat conserved, but can be substituted with two other small aromatic amino acids (phenylalanine or histidine. The S-segment contains a series of serine residues, but in some proteins is also preceded by a conserved LHR sequence. In many dehydrins containing all three of these motifs the S-segment is linked to the K-segment by a GXGGRRKK motif (where X can be any amino acid, suggesting a functional linkage between these two motifs. An analysis of the sequences shows that the dehydrin architecture and several biochemical properties (isoelectric point, molecular mass, and hydrophobicity score are dependent on each other, and that some dehydrin architectures are overexpressed during certain abiotic stress, suggesting that they may be optimized for a specific abiotic stress while others are involved in all forms of dehydration stress (drought, cold, and salinity.

  13. Detecting Statistically Significant Communities of Triangle Motifs in Undirected Networks

    Science.gov (United States)

    2016-04-26

    Granovetter, M. (1983), “The strength of weak ties: A network theory revisited,” Sociological Theory 1 pp. 201-233. [4] Lancichinetti, A., Fortunato, S...AFRL-AFOSR-UK-TR-2015-0025 Detecting Statistically Signicant Communities of Triangle Motifs in Undirected Networks Marcus Perry IMPERIAL COLLEGE OF...triangle motifs in undirected networks 5a.  CONTRACT NUMBER 5b.  GRANT NUMBER FA9550-15-1-0019 5c.  PROGRAM ELEMENT NUMBER 61102F 6. AUTHOR(S) Marcus Perry

  14. Screening of Genetic Switches Based on the Twister Ribozyme Motif.

    Science.gov (United States)

    Felletti, Michele; Klauser, Benedikt; Hartig, Jörg S

    2016-01-01

    The recent description of a new class of small endonucleolytic ribozymes termed twister opened new avenues into the development of artificial riboswitches, providing new tools for the development of artificial genetic circuits in bacteria. Here we present a method to develop new ligand-dependent riboswitches, employing the newly described catalytic motif as an expression platform in conjugation with naturally occurring or in vitro-selected aptameric domains. The twister motif is an outstandingly flexible tool for the development of highly active ribozyme-based riboswitches able to control gene expression in a ligand-dependent manner in Escherichia coli.

  15. Electronic Signatures in Law: 4th Edition

    OpenAIRE

    Mason, Stephen

    2016-01-01

    Stephen Mason is a leading authority on electronic signatures and electronic evidence, having advised global corporations and governments on these topics. He is also the founder and editor of the international open source journal the Digital Evidence and Electronic Signature Law Review. Stephen is an Associate Research Fellow at the IALS.\\ud \\ud This fourth edition of the well-established practitioner text sets out what constitutes an electronic signature; the form an electronic signature can...

  16. Polygraph: Automatically Generating Signatures for Polymorphic Worms

    OpenAIRE

    Newsome, J.; Karp, B.; Song, D.

    2005-01-01

    It is widely believed that content-signature-based intrusion detection systems (IDSes) are easily evaded by polymorphic worms, which vary their payload on every infection attempt. In this paper, we present Polygraph, a signature generation system that successfully produces signatures that match polymorphic worms. Polygraph generates signatures that consist of multiple disjoint content substrings. In doing so, Polygraph leverages our insight that for a real-world exploit to function properly, ...

  17. SIGNCRYPTION BASED ON DIFFERENT DIGITAL SIGNATURE SCHEMES

    OpenAIRE

    Adrian Atanasiu; Laura Savu

    2012-01-01

    This article presents two new signcryption schemes. The first one is based on Schnorr digital signature algorithm and the second one is using Proxy Signature scheme introduced by Mambo. Schnorr Signcryption has been implemented in a program and here are provided the steps of the algorithm, the results and some examples. The Mambo’s Proxy Signature is adapted for Shortened Digital Signature Standard, being part of a new Proxy Signcryption scheme.

  18. 1 CFR 18.7 - Signature.

    Science.gov (United States)

    2010-01-01

    ... under § 18.4(c) may be authenticated as original documents by digital signatures. ... 1 General Provisions 1 2010-01-01 2010-01-01 false Signature. 18.7 Section 18.7 General Provisions... PREPARATION AND TRANSMITTAL OF DOCUMENTS GENERALLY § 18.7 Signature. The original and each duplicate original...

  19. Signature Size: A Key to Status Awareness

    Science.gov (United States)

    Zweigenhaft, Richard L.

    1970-01-01

    Hypothesizing that signature size is related to status, signatures of undergraduates, blue collar workers, and professors were compared and found to be ranked in the above order. Further, case studies of professors revealed a 50 percent increase in size of signature from several months prior to attainment of the Ph. D. to four years afterward. (DB)

  20. Positional bias of general and tissue-specific regulatory motifs in mouse gene promoters

    Directory of Open Access Journals (Sweden)

    Farré Domènec

    2007-12-01

    Full Text Available Abstract Background The arrangement of regulatory motifs in gene promoters, or promoter architecture, is the result of mutation and selection processes that have operated over many millions of years. In mammals, tissue-specific transcriptional regulation is related to the presence of specific protein-interacting DNA motifs in gene promoters. However, little is known about the relative location and spacing of these motifs. To fill this gap, we have performed a systematic search for motifs that show significant bias at specific promoter locations in a large collection of housekeeping and tissue-specific genes. Results We observe that promoters driving housekeeping gene expression are enriched in particular motifs with strong positional bias, such as YY1, which are of little relevance in promoters driving tissue-specific expression. We also identify a large number of motifs that show positional bias in genes expressed in a highly tissue-specific manner. They include well-known tissue-specific motifs, such as HNF1 and HNF4 motifs in liver, kidney and small intestine, or RFX motifs in testis, as well as many potentially novel regulatory motifs. Based on this analysis, we provide predictions for 559 tissue-specific motifs in mouse gene promoters. Conclusion The study shows that motif positional bias is an important feature of mammalian proximal promoters and that it affects both general and tissue-specific motifs. Motif positional constraints define very distinct promoter architectures depending on breadth of expression and type of tissue.

  1. Nephila clavipes Flagelliform silk-like GGX motifs contribute to extensibility and spacer motifs contribute to strength in synthetic spider silk fibers.

    Science.gov (United States)

    Adrianos, Sherry L; Teulé, Florence; Hinman, Michael B; Jones, Justin A; Weber, Warner S; Yarger, Jeffery L; Lewis, Randolph V

    2013-06-10

    Flagelliform spider silk is the most extensible silk fiber produced by orb weaver spiders, though not as strong as the dragline silk of the spider. The motifs found in the core of the Nephila clavipes flagelliform Flag protein are GGX, spacer, and GPGGX. Flag does not contain the polyalanine motif known to provide the strength of dragline silk. To investigate the source of flagelliform fiber strength, four recombinant proteins were produced containing variations of the three core motifs of the Nephila clavipes flagelliform Flag protein that produces this type of fiber. The as-spun fibers were processed in 80% aqueous isopropanol using a standardized process for all four fiber types, which produced improved mechanical properties. Mechanical testing of the recombinant proteins determined that the GGX motif contributes extensibility and the spacer motif contributes strength to the recombinant fibers. Recombinant protein fibers containing the spacer motif were stronger than the proteins constructed without the spacer that contained only the GGX motif or the combination of the GGX and GPGGX motifs. The mechanical and structural X-ray diffraction analysis of the recombinant fibers provide data that suggests a functional role of the spacer motif that produces tensile strength, though the spacer motif is not clearly defined structurally. These results indicate that the spacer is likely a primary contributor of strength, with the GGX motif supplying mobility to the protein network of native N. clavipes flagelliform silk fibers.

  2. Crystal Structure of (+)-[delta]-Cadinene Synthase from Gossypium arboreum and Evolutionary Divergence of Metal Binding Motifs for Catalysis

    Energy Technology Data Exchange (ETDEWEB)

    Gennadios, Heather A.; Gonzalez, Veronica; Di Costanzo, Luigi; Li, Amang; Yu, Fanglei; Miller, David J.; Allemann, Rudolf K.; Christianson, David W.; (UPENN); (Cardiff); (UC)

    2009-09-11

    (+)-{delta}-Cadinene synthase (DCS) from Gossypium arboreum (tree cotton) is a sesquiterpene cyclase that catalyzes the cyclization of farnesyl diphosphate in the first committed step of the biosynthesis of gossypol, a phytoalexin that defends the plant from bacterial and fungal pathogens. Here, we report the X-ray crystal structure of unliganded DCS at 2.4 {angstrom} resolution and the structure of its complex with three putative Mg{sup 2+} ions and the substrate analogue inhibitor 2-fluorofarnesyl diphosphate (2F-FPP) at 2.75 {angstrom} resolution. These structures illuminate unusual features that accommodate the trinuclear metal cluster required for substrate binding and catalysis. Like other terpenoid cyclases, DCS contains a characteristic aspartate-rich D{sup 307}DTYD{sup 311} motif on helix D that interacts with Mg{sub A}{sup 2+} and Mg{sub C}{sup 2+}. However, DCS appears to be unique among terpenoid cyclases in that it does not contain the 'NSE/DTE' motif on helix H that specifically chelates Mg{sub B}{sup 2+}, which is usually found as the signature sequence (N,D)D(L,I,V)X(S,T)XXXE (boldface indicates Mg{sub B}{sup 2+} ligands). Instead, DCS contains a second aspartate-rich motif, D{sup 451}DVAE{sup 455}, that interacts with Mg{sub B}{sup 2+}. In this regard, DCS is more similar to the isoprenoid chain elongation enzyme farnesyl diphosphate synthase, which also contains two aspartate-rich motifs, rather than the greater family of terpenoid cyclases. Nevertheless, the structure of the DCS-2F-FPP complex shows that the structure of the trinuclear magnesium cluster is generally similar to that of other terpenoid cyclases despite the alternative Mg{sub B}{sup 2+} binding motif. Analyses of DCS mutants with alanine substitutions in the D{sup 307}DTYD{sup 311} and D{sup 451}DVAE{sup 455} segments reveal the contributions of these segments to catalysis.

  3. Identification of a Baeyer-Villiger monooxygenase sequence motif

    NARCIS (Netherlands)

    Fraaije, MW; Kamerbeek, NM; van Berkel, WJH; Janssen, DB; Kamerbeek, Nanne M.; Berkel, Willem J.H. van

    2002-01-01

    Baeyer-Villiger monooxygenases (BVMOs) form a distinct class of flavoproteins that catalyze the insertion of an oxygen atom in a C-C bond using dioxygen and NAD(P)H. Using newly characterized BVMO sequences, we have uncovered a BVMO-identifying sequence motif: FXGXXXRXXXW(P/D). Studies with

  4. Learning Cellular Sorting Pathways Using Protein Interactions and Sequence Motifs

    Science.gov (United States)

    Lin, Tien-Ho; Bar-Joseph, Ziv; Murphy, Robert F.

    Proper subcellular localization is critical for proteins to perform their roles in cellular functions. Proteins are transported by different cellular sorting pathways, some of which take a protein through several intermediate locations until reaching its final destination. The pathway a protein is transported through is determined by carrier proteins that bind to specific sequence motifs. In this paper we present a new method that integrates sequence, motif and protein interaction data to model how proteins are sorted through these targeting pathways. We use a hidden Markov model (HMM) to represent protein targeting pathways. The model is able to determine intermediate sorting states and to assign carrier proteins and motifs to the sorting pathways. In simulation studies, we show that the method can accurately recover an underlying sorting model. Using data for yeast, we show that our model leads to accurate prediction of subcellular localization. We also show that the pathways learned by our model recover many known sorting pathways and correctly assign proteins to the path they utilize. The learned model identified new pathways and their putative carriers and motifs and these may represent novel protein sorting mechanisms.

  5. BayesMD: flexible biological modeling for motif discovery

    DEFF Research Database (Denmark)

    Tang, Man-Hung Eric; Krogh, Anders; Winther, Ole

    2008-01-01

    We present BayesMD, a Bayesian Motif Discovery model with several new features. Three different types of biological a priori knowledge are built into the framework in a modular fashion. A mixture of Dirichlets is used as prior over nucleotide probabilities in binding sites. It is trained on trans...

  6. Type 2 diabetes mellitus: phylogenetic motifs for predicting protein ...

    Indian Academy of Sciences (India)

    2007-06-28

    Jun 28, 2007 ... Diabetes mellitus, commonly referred to as diabetes, is a medical condition associated with abnormally high levels of glucose (or sugar) in the blood. Keeping this view, we demonstrate the phylogenetic motifs (PMs) identification in type 2 diabetes mellitus very likely corresponding to protein functional sites.

  7. Glycation ligand binding motif in lactoferrin. Implications in diabetic infection.

    Science.gov (United States)

    Li, Y M

    1998-01-01

    Lactoferrin and lysozyme are two important, naturally occurring antibacterial proteins found in saliva, nasal secretions, milk, mucus, serum and in the lysosomes of neutrophils and macrophages. Both proteins bind specifically to glucose-modified proteins bearing advanced glycation endproducts (AGEs). Exposure to AGE-modified proteins blocks the bacterial agglutination and bacterial killing activities of lactoferrin and also inhibits the bactericidal and enzymatic activity of lysozyme. Peptide mapping by AGE ligand blot revealed two AGE-binding domains in lactoferrin, and a single AGE-binding domain in lysozyme. None of these AGE-binding domains displayed any significant homology in their primary sequences; however, a common 17-18 amino acid cysteine loop motif (CX15-16C) was identified among them, which we named an ABCD motif (AGE-Binding Cysteine-bounded Domain). Similar domains are also present in other antimicrobial proteins such as defesins. Hydrophilicity analysis indicated that each of these ABCD loops is markedly hydrophilic. Synthetic peptides, corresponding to these motifs in lactoferrin and lysozyme, exhibited AGE-binding activity. Since diabetes is associated with abnormally high levels of tissue and serum AGEs, the elevated AGEs may inhibit endogenous antibacterial proteins by binding to the conserved ABCD motif, thereby increasing susceptibility to bacterial infections in diabetic individuals. These results may provide a basis for the development of new approaches to prevent diabetic infections.

  8. Perceptions of Seshoeshoe fabric, naming and meanings of motifs ...

    African Journals Online (AJOL)

    Responses of participants showed that both the dress and fabric are popularly known as seshoeshoe. It was further found that the choice of the fabric has increased in the market due to the wide variety of motifs and colours although the quality of fabric has not improved. There are still problems encountered by dressmakers ...

  9. Biomarker Motif Discovery by Integrating Mass Spectrometry and PPI Network

    Science.gov (United States)

    Zhou, Xiaobo; Wang, Yuan; Wang, Honghui; Pham, Tuan D.; Li, King

    2011-06-01

    Traditional mass spectrometry biomarker discovery studies which focus on single biomarkers or a panel of biomarkers have shown their limitations with low reproducibility. In this paper, we propose a novel biomarker motif discovery approach by integrating both mass spectrometry data and protein interaction network information together to identify biomarkers. A novel Bayesian score method is developed to score the protein subnetwork both from the expression of protein and from the protein interaction network structure. Compared with the previous biomarker discovery method, our biomarker motif identification method not only models the expression of each protein, but also the relationship of proteins affected by the protein-protein interaction network. The experiment results show that our proposed biomarker discovery method has a higher sensitivity and lower false discovery rates than previously used methods. When applying our biomarker motifs discovery approach to the real stroke mass spectrometry data, we can identify several biomarker motifs for ischemic stroke which can achieve a higher classification performance with high biological significance.

  10. DNA regulatory motif selection based on support vector machine ...

    African Journals Online (AJOL)

    Conserved DNA sequences are essential to investigate the regulation and expression of nearby genes. The conserved regions can interact with certain proteins and can potentially determine the transcription speed and amount of the corresponding mRNA in gene replication process. In this paper, motifs of coexpressed ...

  11. Core signalling motif displaying multistability through multi-state enzymes.

    Science.gov (United States)

    Feng, Song; Sáez, Meritxell; Wiuf, Carsten; Feliu, Elisenda; Soyer, Orkun S

    2016-10-01

    Bistability, and more generally multistability, is a key system dynamics feature enabling decision-making and memory in cells. Deciphering the molecular determinants of multistability is thus crucial for a better understanding of cellular pathways and their (re)engineering in synthetic biology. Here, we show that a key motif found predominantly in eukaryotic signalling systems, namely a futile signalling cycle, can display bistability when featuring a two-state kinase. We provide necessary and sufficient mathematical conditions on the kinetic parameters of this motif that guarantee the existence of multiple steady states. These conditions foster the intuition that bistability arises as a consequence of competition between the two states of the kinase. Extending from this result, we find that increasing the number of kinase states linearly translates into an increase in the number of steady states in the system. These findings reveal, to our knowledge, a new mechanism for the generation of bistability and multistability in cellular signalling systems. Further the futile cycle featuring a two-state kinase is among the smallest bistable signalling motifs. We show that multi-state kinases and the described competition-based motif are part of several natural signalling systems and thereby could enable them to implement complex information processing through multistability. These results indicate that multi-state kinases in signalling systems are readily exploited by natural evolution and could equally be used by synthetic approaches for the generation of multistable information processing systems at the cellular level. © 2016 The Authors.

  12. 333 An Examination of the Festival Motif in Femi Osofisan's ...

    African Journals Online (AJOL)

    a vintage and delightful play, which is very aesthetic and scintillating, yet possesses a strong and radical socialist message. Keywords: Festival motif, Morountodun, Dance, Music,. Traditional theatre, Femi Osofisan. Introduction. Ruth Finnegan describes drama as the enactment or representation through actors who imitate ...

  13. Genetic analysis of beta1 integrin "activation motifs" in mice

    DEFF Research Database (Denmark)

    Czuchra, Aleksandra; Meyer, Hannelore; Legate, Kyle R

    2006-01-01

    Akey feature of integrins is their ability to regulate the affinity for ligands, a process termed integrin activation. The final step in integrin activation is talin binding to the NPXY motif of the integrin beta cytoplasmic domains. Talin binding disrupts the salt bridge between the alpha/beta t...

  14. Signatures of a shadow biosphere.

    Science.gov (United States)

    Davies, Paul C W; Benner, Steven A; Cleland, Carol E; Lineweaver, Charles H; McKay, Christopher P; Wolfe-Simon, Felisa

    2009-03-01

    Astrobiologists are aware that extraterrestrial life might differ from known life, and considerable thought has been given to possible signatures associated with weird forms of life on other planets. So far, however, very little attention has been paid to the possibility that our own planet might also host communities of weird life. If life arises readily in Earth-like conditions, as many astrobiologists contend, then it may well have formed many times on Earth itself, which raises the question whether one or more shadow biospheres have existed in the past or still exist today. In this paper, we discuss possible signatures of weird life and outline some simple strategies for seeking evidence of a shadow biosphere.

  15. Epigenetic signatures of cigarette smoking

    OpenAIRE

    Deary, Ian; Joehanes, Roby; Just, Allan C.; Marioni, Riccardo

    2016-01-01

    Background—DNA methylation leaves a long-term signature of smoking exposure and is one potential mechanism by which tobacco exposure predisposes to adverse health outcomes, such as cancers, osteoporosis, lung, and cardiovascular disorders. Methods and Results—To comprehensively determine the association between cigarette smoking and DNA methylation, we conducted a meta-analysis of genome-wide DNA methylation assessed using the Illumina BeadChip 450K array on 15 907 blood-derived DNA samples f...

  16. Sequence alignment reveals possible MAPK docking motifs on HIV proteins.

    Directory of Open Access Journals (Sweden)

    Perry Evans

    Full Text Available Over the course of HIV infection, virus replication is facilitated by the phosphorylation of HIV proteins by human ERK1 and ERK2 mitogen-activated protein kinases (MAPKs. MAPKs are known to phosphorylate their substrates by first binding with them at a docking site. Docking site interactions could be viable drug targets because the sequences guiding them are more specific than phosphorylation consensus sites. In this study we use multiple bioinformatics tools to discover candidate MAPK docking site motifs on HIV proteins known to be phosphorylated by MAPKs, and we discuss the possibility of targeting docking sites with drugs. Using sequence alignments of HIV proteins of different subtypes, we show that MAPK docking patterns previously described for human proteins appear on the HIV matrix, Tat, and Vif proteins in a strain dependent manner, but are absent from HIV Rev and appear on all HIV Nef strains. We revise the regular expressions of previously annotated MAPK docking patterns in order to provide a subtype independent motif that annotates all HIV proteins. One revision is based on a documented human variant of one of the substrate docking motifs, and the other reduces the number of required basic amino acids in the standard docking motifs from two to one. The proposed patterns are shown to be consistent with in silico docking between ERK1 and the HIV matrix protein. The motif usage on HIV proteins is sufficiently different from human proteins in amino acid sequence similarity to allow for HIV specific targeting using small-molecule drugs.

  17. Infrared signature studies of aerospace vehicles

    Science.gov (United States)

    Mahulikar, Shripad P.; Sonawane, Hemant R.; Arvind Rao, G.

    2007-10-01

    Infrared (IR) emissions from aircraft are used to detect, track, and lock-on to the target. MAN Portable Air Defence Systems (MANPADS) have emerged as a major cause of aircraft and helicopter loss. Therefore, IR signature studies are important to counter this threat for survivability enhancement, and are an important aspect of stealth technology. This paper reviews contemporary developments in this discipline, with particular emphasis on IR signature prediction from aerospace vehicles. The role of atmosphere in IR signature analysis, and relation between IR signature level and target susceptibility are illustrated. Also, IR signature suppression systems and countermeasure techniques are discussed, to highlight their effectiveness and implications in terms of penalties.

  18. Time Series Based for Online Signature Verification

    Directory of Open Access Journals (Sweden)

    I Ketut Gede Darma Putra

    2013-11-01

    Full Text Available Signature verification system is to match the tested signature with a claimed signature. This paper proposes time series based for feature extraction method and dynamic time warping for match method. The system made by process of testing 900 signatures belong to 50 participants, 3 signatures for reference and 5 signatures from original user, simple imposters and trained imposters for signatures test. The final result system was tested with 50 participants with 3 references. This test obtained that system accuracy without imposters is 90,44897959% at threshold 44 with rejection errors (FNMR is 5,2% and acceptance errors (FMR is 4,35102%, when with imposters system accuracy is 80,1361% at threshold 27 with error rejection (FNMR is 15,6% and acceptance errors (average FMR is 4,263946%, with details as follows: acceptance errors is 0,391837%, acceptance errors simple imposters is 3,2% and acceptance errors trained imposters is 9,2%.

  19. Searching for non-B DNA-forming motifs using nBMST (non-B DNA Motif Search Tool)

    Science.gov (United States)

    Cer, RZ; Bruce, KH; Donohue, DE; Temiz, NA; Mudunuri, US; Yi, M; Volfovsky, N; Bacolla, A; Luke, BT; Collins; Stephens, RM

    2012-01-01

    This unit describes basic protocols on using the non-B DNA Motif Search Tool (nBMST) to search for sequence motifs predicted to form alternative DNA conformations that differ from the canonical right-handed Watson-Crick double-helix, collectively known as non-B DNA and on using the associated PolyBrowse, a GBrowse (Stein et al., 2002) based genomic browser. The nBMST is a web-based resource that allows users to submit one or more DNA sequences to search for inverted repeats (cruciform DNA), mirror repeats (triplex DNA), direct/tandem repeats (slipped/hairpin structures), G4 motifs (tetraplex, G-quadruplex DNA), alternating purine-pyrimidine tracts (left-handed Z-DNA), and Aphased repeats (static bending). Basic protocol 1 illustrates different ways of submitting sequences, the required file input format, results comprising downloadable Generic Feature Format (GFF) files, static Portable Network Graphics (PNG) images, dynamic PolyBrowse link, and accessing documentation through the Help and Frequently Asked Questions (FAQs) pages. Basic Protocol 2 illustrates a brief overview of some of the PolyBrowse functionalities, particularly with reference to possible associations between predicted non-B DNA forming motifs and disease causing effects. The nBMST is versatile, simple to use, does not require bioinformatics skills, and can be applied to any type of DNA sequences, including viral and bacterial genomes, up to 20 megabytes (MB). PMID:22470144

  20. Motivated proteins: a web application for studying small three-dimensional protein motifs.

    Science.gov (United States)

    Leader, David P; Milner-White, E James

    2009-02-11

    Small loop-shaped motifs are common constituents of the three-dimensional structure of proteins. Typically they comprise between three and seven amino acid residues, and are defined by a combination of dihedral angles and hydrogen bonding partners. The most abundant of these are alphabeta-motifs, asx-motifs, asx-turns, beta-bulges, beta-bulge loops, beta-turns, nests, niches, Schellmann loops, ST-motifs, ST-staples and ST-turns. We have constructed a database of such motifs from a range of high-quality protein structures and built a web application as a visual interface to this. The web application, Motivated Proteins, provides access to these 12 motifs (with 48 sub-categories) in a database of over 400 representative proteins. Queries can be made for specific categories or sub-categories of motif, motifs in the vicinity of ligands, motifs which include part of an enzyme active site, overlapping motifs, or motifs which include a particular amino acid sequence. Individual proteins can be specified, or, where appropriate, motifs for all proteins listed. The results of queries are presented in textual form as an (X)HTML table, and may be saved as parsable plain text or XML. Motifs can be viewed and manipulated either individually or in the context of the protein in the Jmol applet structural viewer. Cartoons of the motifs imposed on a linear representation of protein secondary structure are also provided. Summary information for the motifs is available, as are histograms of amino acid distribution, and graphs of dihedral angles at individual positions in the motifs. Motivated Proteins is a publicly and freely accessible web application that enables protein scientists to study small three-dimensional motifs without requiring knowledge of either Structured Query Language or the underlying database schema.

  1. Motivated Proteins: A web application for studying small three-dimensional protein motifs

    Directory of Open Access Journals (Sweden)

    Milner-White E James

    2009-02-01

    Full Text Available Abstract Background Small loop-shaped motifs are common constituents of the three-dimensional structure of proteins. Typically they comprise between three and seven amino acid residues, and are defined by a combination of dihedral angles and hydrogen bonding partners. The most abundant of these are αβ-motifs, asx-motifs, asx-turns, β-bulges, β-bulge loops, β-turns, nests, niches, Schellmann loops, ST-motifs, ST-staples and ST-turns. We have constructed a database of such motifs from a range of high-quality protein structures and built a web application as a visual interface to this. Description The web application, Motivated Proteins, provides access to these 12 motifs (with 48 sub-categories in a database of over 400 representative proteins. Queries can be made for specific categories or sub-categories of motif, motifs in the vicinity of ligands, motifs which include part of an enzyme active site, overlapping motifs, or motifs which include a particular amino acid sequence. Individual proteins can be specified, or, where appropriate, motifs for all proteins listed. The results of queries are presented in textual form as an (XHTML table, and may be saved as parsable plain text or XML. Motifs can be viewed and manipulated either individually or in the context of the protein in the Jmol applet structural viewer. Cartoons of the motifs imposed on a linear representation of protein secondary structure are also provided. Summary information for the motifs is available, as are histograms of amino acid distribution, and graphs of dihedral angles at individual positions in the motifs. Conclusion Motivated Proteins is a publicly and freely accessible web application that enables protein scientists to study small three-dimensional motifs without requiring knowledge of either Structured Query Language or the underlying database schema.

  2. Enzyme sensitive synthetic polymer micelles based on the azobenzene motif.

    Science.gov (United States)

    Rao, Jingyi; Khan, Anzar

    2013-09-25

    In this study, we investigate the potential of an artificial structural motif, azobenzene, in the preparation of enzyme sensitive polymeric nanostructures. For this purpose, an azobenzene linkage is established at the copolymer junction of an amphiphilic diblock copolymer. This polymer assembles into a micellar structure in water. Treatment with the enzyme azoreductase, in the presence of coenzyme NADPH, results in the cleavage of the azo-based copolymer junction and disruption of the micellar assembly. These results suggest that azobenezene is a useful non-natural structural motif for the preparation of enzyme responsive polymer nanoparticles. Due to the presence of azoreductase in the human intestine, such nanomaterials are anticipated to find applicability in the arena of colon-specific delivery systems.

  3. Identifiability and inference of pathway motifs by epistasis analysis

    Science.gov (United States)

    Phenix, Hilary; Perkins, Theodore; Kærn, Mads

    2013-06-01

    The accuracy of genetic network inference is limited by the assumptions used to determine if one hypothetical model is better than another in explaining experimental observations. Most previous work on epistasis analysis—in which one attempts to infer pathway relationships by determining equivalences among traits following mutations—has been based on Boolean or linear models. Here, we delineate the ultimate limits of epistasis-based inference by systematically surveying all two-gene network motifs and use symbolic algebra with arbitrary regulation functions to examine trait equivalences. Our analysis divides the motifs into equivalence classes, where different genetic perturbations result in indistinguishable experimental outcomes. We demonstrate that this partitioning can reveal important information about network architecture, and show, using simulated data, that it greatly improves the accuracy of genetic network inference methods. Because of the minimal assumptions involved, equivalence partitioning has broad applicability for gene network inference.

  4. Factoring local sequence composition in motif significance analysis.

    Science.gov (United States)

    Ng, Patrick; Keich, Uri

    2008-01-01

    We recently introduced a biologically realistic and reliable significance analysis of the output of a popular class of motif finders. In this paper we further improve our significance analysis by incorporating local base composition information. Relying on realistic biological data simulation, as well as on FDR analysis applied to real data, we show that our method is significantly better than the increasingly popular practice of using the normal approximation to estimate the significance of a finder's output. Finally we turn to leveraging our reliable significance analysis to improve the actual motif finding task. Specifically, endowing a variant of the Gibbs Sampler with our improved significance analysis we demonstrate that de novo finders can perform better than has been perceived. Significantly, our new variant outperforms all the finders reviewed in a recently published comprehensive analysis of the Harbison genome-wide binding location data. Interestingly, many of these finders incorporate additional information such as nucleosome positioning and the significance of binding data.

  5. Distinct configurations of protein complexes and biochemical pathways revealed by epistatic interaction network motifs

    LENUS (Irish Health Repository)

    Casey, Fergal

    2011-08-22

    Abstract Background Gene and protein interactions are commonly represented as networks, with the genes or proteins comprising the nodes and the relationship between them as edges. Motifs, or small local configurations of edges and nodes that arise repeatedly, can be used to simplify the interpretation of networks. Results We examined triplet motifs in a network of quantitative epistatic genetic relationships, and found a non-random distribution of particular motif classes. Individual motif classes were found to be associated with different functional properties, suggestive of an underlying biological significance. These associations were apparent not only for motif classes, but for individual positions within the motifs. As expected, NNN (all negative) motifs were strongly associated with previously reported genetic (i.e. synthetic lethal) interactions, while PPP (all positive) motifs were associated with protein complexes. The two other motif classes (NNP: a positive interaction spanned by two negative interactions, and NPP: a negative spanned by two positives) showed very distinct functional associations, with physical interactions dominating for the former but alternative enrichments, typical of biochemical pathways, dominating for the latter. Conclusion We present a model showing how NNP motifs can be used to recognize supportive relationships between protein complexes, while NPP motifs often identify opposing or regulatory behaviour between a gene and an associated pathway. The ability to use motifs to point toward underlying biological organizational themes is likely to be increasingly important as more extensive epistasis mapping projects in higher organisms begin.

  6. DMINDA: an integrated web server for DNA motif identification and analyses

    Science.gov (United States)

    Ma, Qin; Zhang, Hanyuan; Mao, Xizeng; Zhou, Chuan; Liu, Bingqiang; Chen, Xin; Xu, Ying

    2014-01-01

    DMINDA (DNA motif identification and analyses) is an integrated web server for DNA motif identification and analyses, which is accessible at http://csbl.bmb.uga.edu/DMINDA/. This web site is freely available to all users and there is no login requirement. This server provides a suite of cis-regulatory motif analysis functions on DNA sequences, which are important to elucidation of the mechanisms of transcriptional regulation: (i) de novo motif finding for a given set of promoter sequences along with statistical scores for the predicted motifs derived based on information extracted from a control set, (ii) scanning motif instances of a query motif in provided genomic sequences, (iii) motif comparison and clustering of identified motifs, and (iv) co-occurrence analyses of query motifs in given promoter sequences. The server is powered by a backend computer cluster with over 150 computing nodes, and is particularly useful for motif prediction and analyses in prokaryotic genomes. We believe that DMINDA, as a new and comprehensive web server for cis-regulatory motif finding and analyses, will benefit the genomic research community in general and prokaryotic genome researchers in particular. PMID:24753419

  7. DMINDA: an integrated web server for DNA motif identification and analyses.

    Science.gov (United States)

    Ma, Qin; Zhang, Hanyuan; Mao, Xizeng; Zhou, Chuan; Liu, Bingqiang; Chen, Xin; Xu, Ying

    2014-07-01

    DMINDA (DNA motif identification and analyses) is an integrated web server for DNA motif identification and analyses, which is accessible at http://csbl.bmb.uga.edu/DMINDA/. This web site is freely available to all users and there is no login requirement. This server provides a suite of cis-regulatory motif analysis functions on DNA sequences, which are important to elucidation of the mechanisms of transcriptional regulation: (i) de novo motif finding for a given set of promoter sequences along with statistical scores for the predicted motifs derived based on information extracted from a control set, (ii) scanning motif instances of a query motif in provided genomic sequences, (iii) motif comparison and clustering of identified motifs, and (iv) co-occurrence analyses of query motifs in given promoter sequences. The server is powered by a backend computer cluster with over 150 computing nodes, and is particularly useful for motif prediction and analyses in prokaryotic genomes. We believe that DMINDA, as a new and comprehensive web server for cis-regulatory motif finding and analyses, will benefit the genomic research community in general and prokaryotic genome researchers in particular. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  8. DREME: motif discovery in transcription factor ChIP-seq data.

    Science.gov (United States)

    Bailey, Timothy L

    2011-06-15

    Transcription factor (TF) ChIP-seq datasets have particular characteristics that provide unique challenges and opportunities for motif discovery. Most existing motif discovery algorithms do not scale well to such large datasets, or fail to report many motifs associated with cofactors of the ChIP-ed TF. We present DREME, a motif discovery algorithm specifically designed to find the short, core DNA-binding motifs of eukaryotic TFs, and optimized to analyze very large ChIP-seq datasets in minutes. Using DREME, we discover the binding motifs of the the ChIP-ed TF and many cofactors in mouse ES cell (mESC), mouse erythrocyte and human cell line ChIP-seq datasets. For example, in mESC ChIP-seq data for the TF Esrrb, we discover the binding motifs for eight cofactor TFs important in the maintenance of pluripotency. Several other commonly used algorithms find at most two cofactor motifs in this same dataset. DREME can also perform discriminative motif discovery, and we use this feature to provide evidence that Sox2 and Oct4 do not bind in mES cells as an obligate heterodimer. DREME is much faster than many commonly used algorithms, scales linearly in dataset size, finds multiple, non-redundant motifs and reports a reliable measure of statistical significance for each motif found. DREME is available as part of the MEME Suite of motif-based sequence analysis tools (http://meme.nbcr.net).

  9. A Monte Carlo EM algorithm for de novo motif discovery in biomolecular sequences.

    Science.gov (United States)

    Bi, Chengpeng

    2009-01-01

    Motif discovery methods play pivotal roles in deciphering the genetic regulatory codes (i.e., motifs) in genomes as well as in locating conserved domains in protein sequences. The Expectation Maximization (EM) algorithm is one of the most popular methods used in de novo motif discovery. Based on the position weight matrix (PWM) updating technique, this paper presents a Monte Carlo version of the EM motif-finding algorithm that carries out stochastic sampling in local alignment space to overcome the conventional EM's main drawback of being trapped in a local optimum. The newly implemented algorithm is named as Monte Carlo EM Motif Discovery Algorithm (MCEMDA). MCEMDA starts from an initial model, and then it iteratively performs Monte Carlo simulation and parameter update until convergence. A log-likelihood profiling technique together with the top-k strategy is introduced to cope with the phase shifts and multiple modal issues in motif discovery problem. A novel grouping motif alignment (GMA) algorithm is designed to select motifs by clustering a population of candidate local alignments and successfully applied to subtle motif discovery. MCEMDA compares favorably to other popular PWM-based and word enumerative motif algorithms tested using simulated (l, d)-motif cases, documented prokaryotic, and eukaryotic DNA motif sequences. Finally, MCEMDA is applied to detect large blocks of conserved domains using protein benchmarks and exhibits its excellent capacity while compared with other multiple sequence alignment methods.

  10. Triadic motifs in the dependence networks of virtual societies

    OpenAIRE

    Xie, Wen-Jie; Li, Ming-Xia; Jiang, Zhi-Qiang; Zhou, Wei-Xing

    2014-01-01

    In friendship networks, individuals have different numbers of friends, and the closeness or intimacy between an individual and her friends is heterogeneous. Using a statistical filtering method to identify relationships about who depends on whom, we construct dependence networks (which are directed) from weighted friendship networks of avatars in more than two hundred virtual societies of a massively multiplayer online role-playing game (MMORPG). We investigate the evolution of triadic motifs...

  11. Exon silencing by UAGG motifs in response to neuronal excitation.

    Directory of Open Access Journals (Sweden)

    Ping An

    2007-02-01

    Full Text Available Alternative pre-mRNA splicing plays fundamental roles in neurons by generating functional diversity in proteins associated with the communication and connectivity of the synapse. The CI cassette of the NMDA R1 receptor is one of a variety of exons that show an increase in exon skipping in response to cell excitation, but the molecular nature of this splicing responsiveness is not yet understood. Here we investigate the molecular basis for the induced changes in splicing of the CI cassette exon in primary rat cortical cultures in response to KCl-induced depolarization using an expression assay with a tight neuron-specific readout. In this system, exon silencing in response to neuronal excitation was mediated by multiple UAGG-type silencing motifs, and transfer of the motifs to a constitutive exon conferred a similar responsiveness by gain of function. Biochemical analysis of protein binding to UAGG motifs in extracts prepared from treated and mock-treated cortical cultures showed an increase in nuclear hnRNP A1-RNA binding activity in parallel with excitation. Evidence for the role of the NMDA receptor and calcium signaling in the induced splicing response was shown by the use of specific antagonists, as well as cell-permeable inhibitors of signaling pathways. Finally, a wider role for exon-skipping responsiveness is shown to involve additional exons with UAGG-related silencing motifs, and transcripts involved in synaptic functions. These results suggest that, at the post-transcriptional level, excitable exons such as the CI cassette may be involved in strategies by which neurons mount adaptive responses to hyperstimulation.

  12. Neoanalysis, Orality, and Intertextuality: An Examination of Homeric Motif Transference

    Directory of Open Access Journals (Sweden)

    Jonathan Burgess

    2006-03-01

    Full Text Available In Homeric studies scholars have speculated on the influence of (non-surviving preHomeric material on the Iliad. This article expands this line of argument from an oralist perspective, with reference to modern intertextual theory. It concludes that preHomeric and nonHomeric motifs from oral traditions were transferred into the epic poem, creating an intertextually allusive poetics that would have been recognizable to an early Greek audience informed of mythological traditions.

  13. Motif Subscriber Menonton Channel YouTube Raditya Dika

    OpenAIRE

    Mellyaningsih, Adinda

    2016-01-01

    Penelitian ini dilakukan untuk mengetahui motif para subscriber dalam menonton channelYouTube Raditya Dika. Raditya Dika merupakan YouTuber Indonesia dengan jumlah subscriber terbanyak dan merupakan orang pertama di Indonesia yang mendapatkan penghargaan Certifies Award oleh YouTube. Peneliti menggunakan teori Uses and Gratification dengan empat indikator, yaitu hiburan dan relaksasi, hubungan antar pribadi, mencari informasi, dan persahabatan. Metode dalam penelitian ini adalah online survei...

  14. Motif, the basics: an overview of the widget set

    Energy Technology Data Exchange (ETDEWEB)

    McClurg, F.R.

    1992-10-01

    The Motif library provides programmers with a rich set of tools for building a graphical user interface with a three-dimensional appearance and a consistent method of interaction for controlling an Unix application. This Xt-based, high-level library presents an object-oriented'' approach to program design for programmers and allows end-users the flexibility to modify attributes of the interface.

  15. Motif, the basics: an overview of the widget set

    Energy Technology Data Exchange (ETDEWEB)

    McClurg, F.R.

    1992-10-01

    The Motif library provides programmers with a rich set of tools for building a graphical user interface with a three-dimensional appearance and a consistent method of interaction for controlling an Unix application. This Xt-based, high-level library presents an ``object-oriented`` approach to program design for programmers and allows end-users the flexibility to modify attributes of the interface.

  16. Event Networks and the Identification of Crime Pattern Motifs.

    Directory of Open Access Journals (Sweden)

    Toby Davies

    Full Text Available In this paper we demonstrate the use of network analysis to characterise patterns of clustering in spatio-temporal events. Such clustering is of both theoretical and practical importance in the study of crime, and forms the basis for a number of preventative strategies. However, existing analytical methods show only that clustering is present in data, while offering little insight into the nature of the patterns present. Here, we show how the classification of pairs of events as close in space and time can be used to define a network, thereby generalising previous approaches. The application of graph-theoretic techniques to these networks can then offer significantly deeper insight into the structure of the data than previously possible. In particular, we focus on the identification of network motifs, which have clear interpretation in terms of spatio-temporal behaviour. Statistical analysis is complicated by the nature of the underlying data, and we provide a method by which appropriate randomised graphs can be generated. Two datasets are used as case studies: maritime piracy at the global scale, and residential burglary in an urban area. In both cases, the same significant 3-vertex motif is found; this result suggests that incidents tend to occur not just in pairs, but in fact in larger groups within a restricted spatio-temporal domain. In the 4-vertex case, different motifs are found to be significant in each case, suggesting that this technique is capable of discriminating between clustering patterns at a finer granularity than previously possible.

  17. Insertion of tetracysteine motifs into dopamine transporter extracellular domains.

    Directory of Open Access Journals (Sweden)

    Deanna M Navaroli

    Full Text Available The neuronal dopamine transporter (DAT is a major determinant of extracellular dopamine (DA levels and is the primary target for a variety of addictive and therapeutic psychoactive drugs. DAT is acutely regulated by protein kinase C (PKC activation and amphetamine exposure, both of which modulate DAT surface expression by endocytic trafficking. In order to use live imaging approaches to study DAT endocytosis, methods are needed to exclusively label the DAT surface pool. The use of membrane impermeant, sulfonated biarsenic dyes holds potential as one such approach, and requires introduction of an extracellular tetracysteine motif (tetraCys; CCPGCC to facilitate dye binding. In the current study, we took advantage of intrinsic proline-glycine (Pro-Gly dipeptides encoded in predicted DAT extracellular domains to introduce tetraCys motifs into DAT extracellular loops 2, 3, and 4. [(3H]DA uptake studies, surface biotinylation and fluorescence microscopy in PC12 cells indicate that tetraCys insertion into the DAT second extracellular loop results in a functional transporter that maintains PKC-mediated downregulation. Introduction of tetraCys into extracellular loops 3 and 4 yielded DATs with severely compromised function that failed to mature and traffic to the cell surface. This is the first demonstration of successful introduction of a tetracysteine motif into a DAT extracellular domain, and may hold promise for use of biarsenic dyes in live DAT imaging studies.

  18. Maximum likelihood density modification by pattern recognition of structural motifs

    Science.gov (United States)

    Terwilliger, Thomas C.

    2004-04-13

    An electron density for a crystallographic structure having protein regions and solvent regions is improved by maximizing the log likelihood of a set of structures factors {F.sub.h } using a local log-likelihood function: (x)+p(.rho.(x).vertline.SOLV)p.sub.SOLV (x)+p(.rho.(x).vertline.H)p.sub.H (x)], where p.sub.PROT (x) is the probability that x is in the protein region, p(.rho.(x).vertline.PROT) is the conditional probability for .rho.(x) given that x is in the protein region, and p.sub.SOLV (x) and p(.rho.(x).vertline.SOLV) are the corresponding quantities for the solvent region, p.sub.H (x) refers to the probability that there is a structural motif at a known location, with a known orientation, in the vicinity of the point x; and p(.rho.(x).vertline.H) is the probability distribution for electron density at this point given that the structural motif actually is present. One appropriate structural motif is a helical structure within the crystallographic structure.

  19. Interlinking motifs and entropy landscapes of statistically interacting particles

    Directory of Open Access Journals (Sweden)

    P. Lu

    2012-03-01

    Full Text Available The s=1/2 Ising chain with uniform nearest-neighbor and next-nearest-neighbor coupling is used to construct a system of floating particles characterized by motifs of up to six consecutive local spins. The spin couplings cause the assembly of particles which, in turn, remain free of interaction energies even at high density. All microstates are configurations of particles from one of three different sets, excited from pseudo-vacua associated with ground states of periodicities one, two, and four. The motifs of particles and elements of pseudo-vacuum interlink in two shared site variables. The statistical interaction between particles is encoded in a generalized Pauli principle, describing how the placement of one particle modifies the options for placing further particles. In the statistical mechanical analysis arbitrary energies can be assigned to all particle species. The entropy is a function of the particle populations. The statistical interaction specifications are transparently built into that expression. The energies and structures of the particles alone govern the ordering at low temperature. Under special circumstances the particles can be replaced by more fundamental particles with shorter motifs that interlink in only one shared site variable. Structures emerge from interactions on two levels: particles with shapes from coupled spins and long-range ordering tendencies from statistically interacting particles with shapes.

  20. ROMANIAN TRADITIONAL MOTIF ELEMENT OF MODERNITY IN CLOTHING

    Directory of Open Access Journals (Sweden)

    ŞUTEU Marius Darius

    2017-05-01

    Full Text Available In this paper are presented the phases for improving from an aesthetic point of view a clothing item, the T-shirt for women using software design patterns, computerised graphics and textile different modern technologies including: industrial embroidery, digital printing, sublimation. In the first phase a documentation was prepared in the University of Oradea and traditional motif was selected from a collection comprising a number of Romanian traditional motifs from different parts of the country and were reintepreted and stylized whilst preserving the symbolism and color range specified to the area. For the styling phase was used CorelDraw vector graphics program that allows changing the shape, size and color of the drawings without affecting the identity of the pattern. The embroidery was done using BERNINA Embroidery Software Designer Plus Software. This software allows you to export the model to any domestic or industrial embroidery machine regardless of brand. Finally we observed the resistance of the printed and embroided model to various: elasticity, resistance to abrasion and a sensory analysis on the preservation of color. After testing we noticed the imprint resistance applied to the fabric, resulting in a quality that makes possible to keep the Romanian traditional motif from generation to generation.

  1. Multitasking of neuropeptide Y through the lens of motifs.

    Science.gov (United States)

    Myslobodsky, Michael

    2009-01-01

    Networks controlling ingestion-related peptides are also known to be the targets and signals for numerous other systems. Yet, their topological properties are still ill understood. The Ingenuity Pathway Analysis (IPA) was employed to represent molecules engaged in feeding as nodes, and the interactions between them as edges. Using extracted molecules as 'seeds' for core analysis it was possible to scrutinize some of the complex relationships of sub-networks and the so-called 'motifs' well outside the neighborhoods of their classical roles. Contrary to the requirements for modular structure, the orexigenic and anorexigenic neuropeptides do not represent two types of modules. They are densely interconnected. Functional annotations showed that the same molecules are recruited ad-hoc from a larger 'repository' and assembled into dynamic networks for executing diverse physiological functions and behaviors. Some molecules clustered in motifs appear as the multipurpose entities for cell-to-cell signaling, organismal development, cellular movement, growth and proliferation, endocrine system development and tissue morphology, etc. that apparently become active in early ontogeny. Based mostly on neuropeptide Y (NPY), my arguments here will focus on the potential benefits of exploring motifs in network controlling ingestion for generating insights for polypharmacy of obesity-related targets and co-morbid disorders. Recent patents describing new NPY receptor antagonists directed to treat obesity and cardiovascular disorders were cited.

  2. Motif structure and cooperation in real-world complex networks

    Science.gov (United States)

    Salehi, Mostafa; Rabiee, Hamid R.; Jalili, Mahdi

    2010-12-01

    Networks of dynamical nodes serve as generic models for real-world systems in many branches of science ranging from mathematics to physics, technology, sociology and biology. Collective behavior of agents interacting over complex networks is important in many applications. The cooperation between selfish individuals is one of the most interesting collective phenomena. In this paper we address the interplay between the motifs’ cooperation properties and their abundance in a number of real-world networks including yeast protein-protein interaction, human brain, protein structure, email communication, dolphins’ social interaction, Zachary karate club and Net-science coauthorship networks. First, the amount of cooperativity for all possible undirected subgraphs with three to six nodes is calculated. To this end, the evolutionary dynamics of the Prisoner’s Dilemma game is considered and the cooperativity of each subgraph is calculated as the percentage of cooperating agents at the end of the simulation time. Then, the three- to six-node motifs are extracted for each network. The significance of the abundance of a motif, represented by a Z-value, is obtained by comparing them with some properly randomized versions of the original network. We found that there is always a group of motifs showing a significant inverse correlation between their cooperativity amount and Z-value, i.e. the more the Z-value the less the amount of cooperativity. This suggests that networks composed of well-structured units do not have good cooperativity properties.

  3. MAR characteristic motifs mediate episomal vector in CHO cells.

    Science.gov (United States)

    Lin, Yan; Li, Zhaoxi; Wang, Tianyun; Wang, Xiaoyin; Wang, Li; Dong, Weihua; Jing, Changqin; Yang, Xianjun

    2015-04-01

    An ideal gene therapy vector should enable persistent transgene expression without limitations in safety and reproducibility. Recent researches' insight into the ability of chromosomal matrix attachment regions (MARs) to mediate episomal maintenance of genetic elements allowed the development of a circular episomal vector. Although a MAR-mediated engineered vector has been developed, little is known on which motifs of MAR confer this function during interaction with the host genome. Here, we report an artificially synthesized DNA fragment containing only characteristic motif sequences that served as an alternative to human beta-interferon matrix attachment region sequence. The potential of the vector to mediate gene transfer in CHO cells was investigated. The short synthetic MAR motifs were found to mediate episomal vector at a low copy number for many generations without integration into the host genome. Higher transgene expression was maintained for at least 4 months. In addition, MAR was maintained episomally and conferred sustained EGFP expression even in nonselective CHO cells. All the results demonstrated that MAR characteristic sequence-based vector can function as stable episomes in CHO cells, supporting long-term and effective transgene expression. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Event Networks and the Identification of Crime Pattern Motifs

    Science.gov (United States)

    2015-01-01

    In this paper we demonstrate the use of network analysis to characterise patterns of clustering in spatio-temporal events. Such clustering is of both theoretical and practical importance in the study of crime, and forms the basis for a number of preventative strategies. However, existing analytical methods show only that clustering is present in data, while offering little insight into the nature of the patterns present. Here, we show how the classification of pairs of events as close in space and time can be used to define a network, thereby generalising previous approaches. The application of graph-theoretic techniques to these networks can then offer significantly deeper insight into the structure of the data than previously possible. In particular, we focus on the identification of network motifs, which have clear interpretation in terms of spatio-temporal behaviour. Statistical analysis is complicated by the nature of the underlying data, and we provide a method by which appropriate randomised graphs can be generated. Two datasets are used as case studies: maritime piracy at the global scale, and residential burglary in an urban area. In both cases, the same significant 3-vertex motif is found; this result suggests that incidents tend to occur not just in pairs, but in fact in larger groups within a restricted spatio-temporal domain. In the 4-vertex case, different motifs are found to be significant in each case, suggesting that this technique is capable of discriminating between clustering patterns at a finer granularity than previously possible. PMID:26605544

  5. An update on cell surface proteins containing extensin-motifs.

    Science.gov (United States)

    Borassi, Cecilia; Sede, Ana R; Mecchia, Martin A; Salgado Salter, Juan D; Marzol, Eliana; Muschietti, Jorge P; Estevez, Jose M

    2016-01-01

    In recent years it has become clear that there are several molecular links that interconnect the plant cell surface continuum, which is highly important in many biological processes such as plant growth, development, and interaction with the environment. The plant cell surface continuum can be defined as the space that contains and interlinks the cell wall, plasma membrane and cytoskeleton compartments. In this review, we provide an updated view of cell surface proteins that include modular domains with an extensin (EXT)-motif followed by a cytoplasmic kinase-like domain, known as PERKs (for proline-rich extensin-like receptor kinases); with an EXT-motif and an actin binding domain, known as formins; and with extracellular hybrid-EXTs. We focus our attention on the EXT-motifs with the short sequence Ser-Pro(3-5), which is found in several different protein contexts within the same extracellular space, highlighting a putative conserved structural and functional role. A closer understanding of the dynamic regulation of plant cell surface continuum and its relationship with the downstream signalling cascade is a crucial forthcoming challenge. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  6. Cryptoschemes Based on New Signature Formation Mechanism

    Directory of Open Access Journals (Sweden)

    A.A.Moldovyan

    2006-12-01

    Full Text Available Several variants of new digital signature schemes (DSS based on the discrete logarithm and factorization problems have been proposed. Considered DSS are characterized in that a novel mechanism of the signature generation is used, in which two parameters of the (k,S or (R,S signature are defined after solving a system of two congruences. In the case of composite modulus additional restrictions conditions have been introduced for selection of the public key.

  7. Cryptographic key generation using handwritten signature

    Science.gov (United States)

    Freire-Santos, M.; Fierrez-Aguilar, J.; Ortega-Garcia, J.

    2006-04-01

    Based on recent works showing the feasibility of key generation using biometrics, we study the application of handwritten signature to cryptography. Our signature-based key generation scheme implements the cryptographic construction named fuzzy vault. The use of distinctive signature features suited for the fuzzy vault is discussed and evaluated. Experimental results are reported, including error rates to unlock the secret data by using both random and skilled forgeries from the MCYT database.

  8. Molecular Signatures in Urologic Tumors

    Directory of Open Access Journals (Sweden)

    Spencer Larkin

    2013-09-01

    Full Text Available Urologic tumors continue to represent a huge fraction of cancer cases in the United States, with over 376,310 estimated new diagnoses in 2013. As with many types of tumors, urologic tumors vary greatly in their phenotype, ranging from minimally invasive to malignancies possessing great metastatic potential. The increasing need for more efficient and less invasive methods of cancer detection, as well as the ability to predict severity of the disease phenotype is readily evident—yet reliable methods remain elusive in a clinical setting today. Comprehensive panels of gene clusters are being developed toward the generation of molecular signatures in order to better diagnose urologic malignancies, and identify effective treatment strategies in the emerging era of personalized medicine. In this review, we discuss the current literature on the credibility and biomarker value of such molecular signatures in the context of clinical significance relating to the pathological aggressiveness of urologic tumors (prostate, bladder and renal cancer—also exploiting their predictive potential in the response to treatment.

  9. A novel Bayesian DNA motif comparison method for clustering and retrieval.

    Directory of Open Access Journals (Sweden)

    Naomi Habib

    2008-02-01

    Full Text Available Characterizing the DNA-binding specificities of transcription factors is a key problem in computational biology that has been addressed by multiple algorithms. These usually take as input sequences that are putatively bound by the same factor and output one or more DNA motifs. A common practice is to apply several such algorithms simultaneously to improve coverage at the price of redundancy. In interpreting such results, two tasks are crucial: clustering of redundant motifs, and attributing the motifs to transcription factors by retrieval of similar motifs from previously characterized motif libraries. Both tasks inherently involve motif comparison. Here we present a novel method for comparing and merging motifs, based on Bayesian probabilistic principles. This method takes into account both the similarity in positional nucleotide distributions of the two motifs and their dissimilarity to the background distribution. We demonstrate the use of the new comparison method as a basis for motif clustering and retrieval procedures, and compare it to several commonly used alternatives. Our results show that the new method outperforms other available methods in accuracy and sensitivity. We incorporated the resulting motif clustering and retrieval procedures in a large-scale automated pipeline for analyzing DNA motifs. This pipeline integrates the results of various DNA motif discovery algorithms and automatically merges redundant motifs from multiple training sets into a coherent annotated library of motifs. Application of this pipeline to recent genome-wide transcription factor location data in S. cerevisiae successfully identified DNA motifs in a manner that is as good as semi-automated analysis reported in the literature. Moreover, we show how this analysis elucidates the mechanisms of condition-specific preferences of transcription factors.

  10. An Arbitrated Quantum Signature Scheme without Entanglement*

    Science.gov (United States)

    Li, Hui-Ran; Luo, Ming-Xing; Peng, Dai-Yuan; Wang, Xiao-Jun

    2017-09-01

    Several quantum signature schemes are recently proposed to realize secure signatures of quantum or classical messages. Arbitrated quantum signature as one nontrivial scheme has attracted great interests because of its usefulness and efficiency. Unfortunately, previous schemes cannot against Trojan horse attack and DoS attack and lack of the unforgeability and the non-repudiation. In this paper, we propose an improved arbitrated quantum signature to address these secure issues with the honesty arbitrator. Our scheme takes use of qubit states not entanglements. More importantly, the qubit scheme can achieve the unforgeability and the non-repudiation. Our scheme is also secure for other known quantum attacks.

  11. On reliable discovery of molecular signatures

    Directory of Open Access Journals (Sweden)

    Björkegren Johan

    2009-01-01

    Full Text Available Abstract Background Molecular signatures are sets of genes, proteins, genetic variants or other variables that can be used as markers for a particular phenotype. Reliable signature discovery methods could yield valuable insight into cell biology and mechanisms of human disease. However, it is currently not clear how to control error rates such as the false discovery rate (FDR in signature discovery. Moreover, signatures for cancer gene expression have been shown to be unstable, that is, difficult to replicate in independent studies, casting doubts on their reliability. Results We demonstrate that with modern prediction methods, signatures that yield accurate predictions may still have a high FDR. Further, we show that even signatures with low FDR may fail to replicate in independent studies due to limited statistical power. Thus, neither stability nor predictive accuracy are relevant when FDR control is the primary goal. We therefore develop a general statistical hypothesis testing framework that for the first time provides FDR control for signature discovery. Our method is demonstrated to be correct in simulation studies. When applied to five cancer data sets, the method was able to discover molecular signatures with 5% FDR in three cases, while two data sets yielded no significant findings. Conclusion Our approach enables reliable discovery of molecular signatures from genome-wide data with current sample sizes. The statistical framework developed herein is potentially applicable to a wide range of prediction problems in bioinformatics.

  12. Institute of Geophysics, Planetary Physics, and Signatures

    Data.gov (United States)

    Federal Laboratory Consortium — The Institute of Geophysics, Planetary Physics, and Signatures at Los Alamos National Laboratory is committed to promoting and supporting high quality, cutting-edge...

  13. Novel Quantum Proxy Signature without Entanglement

    Science.gov (United States)

    Xu, Guang-bao

    2015-08-01

    Proxy signature is an important research topic in classic cryptography since it has many application occasions in our real life. But only a few quantum proxy signature schemes have been proposed up to now. In this paper, we propose a quantum proxy signature scheme, which is designed based on quantum one-time pad. Our scheme can be realized easily since it only uses single-particle states. Security analysis shows that it is secure and meets all the properties of a proxy signature, such as verifiability, distinguishability, unforgeability and undeniability.

  14. Predicting tissue specific cis-regulatory modules in the human genome using pairs of co-occurring motifs

    Directory of Open Access Journals (Sweden)

    Girgis Hani Z

    2012-02-01

    Full Text Available Abstract Background Researchers seeking to unlock the genetic basis of human physiology and diseases have been studying gene transcription regulation. The temporal and spatial patterns of gene expression are controlled by mainly non-coding elements known as cis-regulatory modules (CRMs and epigenetic factors. CRMs modulating related genes share the regulatory signature which consists of transcription factor (TF binding sites (TFBSs. Identifying such CRMs is a challenging problem due to the prohibitive number of sequence sets that need to be analyzed. Results We formulated the challenge as a supervised classification problem even though experimentally validated CRMs were not required. Our efforts resulted in a software system named CrmMiner. The system mines for CRMs in the vicinity of related genes. CrmMiner requires two sets of sequences: a mixed set and a control set. Sequences in the vicinity of the related genes comprise the mixed set, whereas the control set includes random genomic sequences. CrmMiner assumes that a large percentage of the mixed set is made of background sequences that do not include CRMs. The system identifies pairs of closely located motifs representing vertebrate TFBSs that are enriched in the training mixed set consisting of 50% of the gene loci. In addition, CrmMiner selects a group of the enriched pairs to represent the tissue-specific regulatory signature. The mixed and the control sets are searched for candidate sequences that include any of the selected pairs. Next, an optimal Bayesian classifier is used to distinguish candidates found in the mixed set from their control counterparts. Our study proposes 62 tissue-specific regulatory signatures and putative CRMs for different human tissues and cell types. These signatures consist of assortments of ubiquitously expressed TFs and tissue-specific TFs. Under controlled settings, CrmMiner identified known CRMs in noisy sets up to 1:25 signal-to-noise ratio. CrmMiner was

  15. Predicting tissue specific cis-regulatory modules in the human genome using pairs of co-occurring motifs.

    Science.gov (United States)

    Girgis, Hani Z; Ovcharenko, Ivan

    2012-02-07

    Researchers seeking to unlock the genetic basis of human physiology and diseases have been studying gene transcription regulation. The temporal and spatial patterns of gene expression are controlled by mainly non-coding elements known as cis-regulatory modules (CRMs) and epigenetic factors. CRMs modulating related genes share the regulatory signature which consists of transcription factor (TF) binding sites (TFBSs). Identifying such CRMs is a challenging problem due to the prohibitive number of sequence sets that need to be analyzed. We formulated the challenge as a supervised classification problem even though experimentally validated CRMs were not required. Our efforts resulted in a software system named CrmMiner. The system mines for CRMs in the vicinity of related genes. CrmMiner requires two sets of sequences: a mixed set and a control set. Sequences in the vicinity of the related genes comprise the mixed set, whereas the control set includes random genomic sequences. CrmMiner assumes that a large percentage of the mixed set is made of background sequences that do not include CRMs. The system identifies pairs of closely located motifs representing vertebrate TFBSs that are enriched in the training mixed set consisting of 50% of the gene loci. In addition, CrmMiner selects a group of the enriched pairs to represent the tissue-specific regulatory signature. The mixed and the control sets are searched for candidate sequences that include any of the selected pairs. Next, an optimal Bayesian classifier is used to distinguish candidates found in the mixed set from their control counterparts. Our study proposes 62 tissue-specific regulatory signatures and putative CRMs for different human tissues and cell types. These signatures consist of assortments of ubiquitously expressed TFs and tissue-specific TFs. Under controlled settings, CrmMiner identified known CRMs in noisy sets up to 1:25 signal-to-noise ratio. CrmMiner was 21-75% more precise than a related CRM

  16. Strategies for the Analysis of Bam Recognition Motifs in Outer Membrane Proteins.

    Science.gov (United States)

    Paramasivam, Nagarajan; Linke, Dirk

    2015-01-01

    Well-structured proteins interact with other proteins through surface-surface interactions. In such cases, the residues that form the interacting surface are not necessarily neighboring residues on the level of protein sequence. In contrast, unfolded or partially unfolded proteins can interact with other proteins through defined linear motifs. In the case of the β-barrel assembly machinery (BAM) in the outer membrane of Gram-negative bacteria, unfolded β-barrel proteins are recognized through a C-terminal linear motif, and are inserted into the membrane. While the exact mechanism of recognition is still under investigation, it has been shown that mutations in the recognition motif can partially or completely abolish membrane insertion. In this chapter, we demonstrate the workflow for motif discovery, motif extraction, and motif visualization on the example of the C-terminal motifs in transmembrane β-barrel proteins.

  17. Distinguishing between biochemical and cellular function: Are there peptide signatures for cellular function of proteins?

    Science.gov (United States)

    Jain, Shruti; Bhattacharyya, Kausik; Bakshi, Rachit; Narang, Ankita; Brahmachari, Vani

    2017-04-01

    The genome annotation and identification of gene function depends on conserved biochemical activity. However, in the cell, proteins with the same biochemical function can participate in different cellular pathways and cannot complement one another. Similarly, two proteins of very different biochemical functions are put in the same class of cellular function; for example, the classification of a gene as an oncogene or a tumour suppressor gene is not related to its biochemical function, but is related to its cellular function. We have taken an approach to identify peptide signatures for cellular function in proteins with known biochemical function. ATPases as a test case, we classified ATPases (2360 proteins) and kinases (517 proteins) from the human genome into different cellular function categories such as transcriptional, replicative, and chromatin remodelling proteins. Using publicly available tool, MEME, we identify peptide signatures shared among the members of a given category but not between cellular functional categories; for example, no motif sharing is seen between chromatin remodelling and transporter ATPases, similarly between receptor Serine/Threonine Kinase and Receptor Tyrosine Kinase. There are motifs shared within each category with significant E value and high occurrence. This concept of signature for cellular function was applied to developmental regulators, the polycomb and trithorax proteins which led to the prediction of the role of INO80, a chromatin remodelling protein, in development. This has been experimentally validated earlier for its role in homeotic gene regulation and its interaction with regulatory complexes like the Polycomb and Trithorax complex. Proteins 2017; 85:682-693. © 2016 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  18. Association between targeted somatic mutation (TSM) signatures and HGS-OvCa progression.

    Science.gov (United States)

    Lindley, Robyn A; Humbert, Patrick; Larner, Cliff; Akmeemana, Eric H; Pendlebury, Christopher R R

    2016-09-01

    Evidence already exists that the activation-induced cytidine deaminase (AID/APOBEC) and the adenosine deaminase (ADAR) families of enzymes are implicated as powerful mutagens in oncogenic processes in many somatic tissues. Each deaminase is identified by the DNA or RNA nucleotide sequence ("motif") surrounding the nucleotide targeted for deamination. The primary objective of this study is to develop an in silico approach to identify nucleotide sequence changes of the target motifs of key deaminases during oncogenesis. If successful, a secondary objective is to investigate if such changes are associated with disease progression indicators that include disease stage and progression-free survival time. Using a discovery cohort of 194 high-grade serous ovarian adenocarcinoma (HGS-OvCa) exomes, the results confirm the ability of the novel in silico approach used to identify changes in the preferred target motifs for AID, APOBEC3G, APOBEC3B, and ADAR1 during oncogenesis. Using this approach, a set of new cancer-progression associated signatures (C-PASs) were identified. Furthermore, it was found that the C-PAS identified can be used to differentiate between the cohort of patients that remained progression-free for longer than 60 months, from those in which disease progressed within 60 months (sensitivity 95%, specificity 90%). The spectrum of outcomes observed here could provide a foundation for future clinical assessment of susceptibility variants in ovarian, and several other cancers as disease progresses. The ability of the in silico methodology used to identify changes in deaminase motifs during oncogenesis also suggests new links between immune system function and tumorigenesis. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  19. Evolutionarily conserved bias of amino-acid usage refines the definition of PDZ-binding motif

    Directory of Open Access Journals (Sweden)

    Launey Thomas

    2011-06-01

    Full Text Available Abstract Background The interactions between PDZ (PSD-95, Dlg, ZO-1 domains and PDZ-binding motifs play central roles in signal transductions within cells. Proteins with PDZ domains bind to PDZ-binding motifs almost exclusively when the motifs are located at the carboxyl (C- terminal ends of their binding partners. However, it remains little explored whether PDZ-binding motifs show any preferential location at the C-terminal ends of proteins, at genome-level. Results Here, we examined the distribution of the type-I (x-x-S/T-x-I/L/V or type-II (x-x-V-x-I/V PDZ-binding motifs in proteins encoded in the genomes of five different species (human, mouse, zebrafish, fruit fly and nematode. We first established that these PDZ-binding motifs are indeed preferentially present at their C-terminal ends. Moreover, we found specific amino acid (AA bias for the 'x' positions in the motifs at the C-terminal ends. In general, hydrophilic AAs were favored. Our genomics-based findings confirm and largely extend the results of previous interaction-based studies, allowing us to propose refined consensus sequences for all of the examined PDZ-binding motifs. An ontological analysis revealed that the refined motifs are functionally relevant since a large fraction of the proteins bearing the motif appear to be involved in signal transduction. Furthermore, co-precipitation experiments confirmed two new protein interactions predicted by our genomics-based approach. Finally, we show that influenza virus pathogenicity can be correlated with PDZ-binding motif, with high-virulence viral proteins bearing a refined PDZ-binding motif. Conclusions Our refined definition of PDZ-binding motifs should provide important clues for identifying functional PDZ-binding motifs and proteins involved in signal transduction.

  20. IncMD: incremental trie-based structural motif discovery algorithm.

    Science.gov (United States)

    Badr, Ghada; Al-Turaiki, Isra; Turcotte, Marcel; Mathkour, Hassan

    2014-10-01

    The discovery of common RNA secondary structure motifs is an important problem in bioinformatics. The presence of such motifs is usually associated with key biological functions. However, the identification of structural motifs is far from easy. Unlike motifs in sequences, which have conserved bases, structural motifs have common structure arrangements even if the underlying sequences are different. Over the past few years, hundreds of algorithms have been published for the discovery of sequential motifs, while less work has been done for the structural motifs case. Current structural motif discovery algorithms are limited in terms of accuracy and scalability. In this paper, we present an incremental and scalable algorithm for discovering RNA secondary structure motifs, namely IncMD. We consider the structural motif discovery as a frequent pattern mining problem and tackle it using a modified a priori algorithm. IncMD uses data structures, trie-based linked lists of prefixes (LLP), to accelerate the search and retrieval of patterns, support counting, and candidate generation. We modify the candidate generation step in order to adapt it to the RNA secondary structure representation. IncMD constructs the frequent patterns incrementally from RNA secondary structure basic elements, using nesting and joining operations. The notion of a motif group is introduced in order to simulate an alignment of motifs that only differ in the number of unpaired bases. In addition, we use a cluster beam approach to select motifs that will survive to the next iterations of the search. Results indicate that IncMD can perform better than some of the available structural motif discovery algorithms in terms of sensitivity (Sn), positive predictive value (PPV), and specificity (Sp). The empirical results also show that the algorithm is scalable and runs faster than all of the compared algorithms.

  1. Motif discovery with data mining in 3D protein structure databases: discovery, validation and prediction of the U-shape zinc binding ("Huf-Zinc") motif.

    Science.gov (United States)

    Maurer-Stroh, Sebastian; Gao, He; Han, Hao; Baeten, Lies; Schymkowitz, Joost; Rousseau, Frederic; Zhang, Louxin; Eisenhaber, Frank

    2013-02-01

    Data mining in protein databases, derivatives from more fundamental protein 3D structure and sequence databases, has considerable unearthed potential for the discovery of sequence motif--structural motif--function relationships as the finding of the U-shape (Huf-Zinc) motif, originally a small student's project, exemplifies. The metal ion zinc is critically involved in universal biological processes, ranging from protein-DNA complexes and transcription regulation to enzymatic catalysis and metabolic pathways. Proteins have evolved a series of motifs to specifically recognize and bind zinc ions. Many of these, so called zinc fingers, are structurally independent globular domains with discontinuous binding motifs made up of residues mostly far apart in sequence. Through a systematic approach starting from the BRIX structure fragment database, we discovered that there exists another predictable subset of zinc-binding motifs that not only have a conserved continuous sequence pattern but also share a characteristic local conformation, despite being included in totally different overall folds. While this does not allow general prediction of all Zn binding motifs, a HMM-based web server, Huf-Zinc, is available for prediction of these novel, as well as conventional, zinc finger motifs in protein sequences. The Huf-Zinc webserver can be freely accessed through this URL (http://mendel.bii.a-star.edu.sg/METHODS/hufzinc/).

  2. Analysis of signature wrapping attacks and countermeasures

    DEFF Research Database (Denmark)

    Gajek, Sebastian; Jensen, Meiko; Liao, Lijun

    2009-01-01

    In recent research it turned out that Boolean verification, of digital signatures in the context of WSSecurity, is likely to fail: If parts of a SOAP message, are signed and the signature verification applied to, the whole document returns true, then nevertheless the, document may have been...

  3. Prediction of soil effects on GPR signatures

    NARCIS (Netherlands)

    Rhebergen, J.B.; Lensen, H.A.; Wijk, C.V. van; Hendrickx, J.M.H.; Dam, R. van; Borchers, B.

    2004-01-01

    In previous work we have shown that GPR signatures are affected by soil texture and soil water content. In this contribution we will use a three dimensional electromagnetic model and a hydrological soil model to explore in more detail the relationships between GPR signatures, soil physical

  4. Measuring ship acoustic signatures against mine threat

    NARCIS (Netherlands)

    Jong, C.A.F. de; Quesson, B.A.J.; Ainslie, M.A.; Vermeulen, R.C.N.

    2012-01-01

    The NATO standard ‘AMP-15’ [1] provides procedures for the measurement and reporting of the acoustic signature of ships and for the establishment of acoustic signature goals to counter the naval mine threat. Measurements are carried out at dedicated shallow water acoustic ranges. Measurements

  5. 21 CFR 11.50 - Signature manifestations.

    Science.gov (United States)

    2010-04-01

    ... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ELECTRONIC RECORDS; ELECTRONIC SIGNATURES Electronic Records § 11.50 Signature manifestations. (a) Signed electronic... the same controls as for electronic records and shall be included as part of any human readable form...

  6. DNA nanotechnology based on i-motif structures.

    Science.gov (United States)

    Dong, Yuanchen; Yang, Zhongqiang; Liu, Dongsheng

    2014-06-17

    CONSPECTUS: Most biological processes happen at the nanometer scale, and understanding the energy transformations and material transportation mechanisms within living organisms has proved challenging. To better understand the secrets of life, researchers have investigated artificial molecular motors and devices over the past decade because such systems can mimic certain biological processes. DNA nanotechnology based on i-motif structures is one system that has played an important role in these investigations. In this Account, we summarize recent advances in functional DNA nanotechnology based on i-motif structures. The i-motif is a DNA quadruplex that occurs as four stretches of cytosine repeat sequences form C·CH(+) base pairs, and their stabilization requires slightly acidic conditions. This unique property has produced the first DNA molecular motor driven by pH changes. The motor is reliable, and studies show that it is capable of millisecond running speeds, comparable to the speed of natural protein motors. With careful design, the output of these types of motors was combined to drive micrometer-sized cantilevers bend. Using established DNA nanostructure assembly and functionalization methods, researchers can easily integrate the motor within other DNA assembled structures and functional units, producing DNA molecular devices with new functions such as suprahydrophobic/suprahydrophilic smart surfaces that switch, intelligent nanopores triggered by pH changes, molecular logic gates, and DNA nanosprings. Recently, researchers have produced motors driven by light and electricity, which have allowed DNA motors to be integrated within silicon-based nanodevices. Moreover, some devices based on i-motif structures have proven useful for investigating processes within living cells. The pH-responsiveness of the i-motif structure also provides a way to control the stepwise assembly of DNA nanostructures. In addition, because of the stability of the i-motif, this

  7. Short sequence motifs, overrepresented in mammalian conservednon-coding sequences

    Energy Technology Data Exchange (ETDEWEB)

    Minovitsky, Simon; Stegmaier, Philip; Kel, Alexander; Kondrashov,Alexey S.; Dubchak, Inna

    2007-02-21

    Background: A substantial fraction of non-coding DNAsequences of multicellular eukaryotes is under selective constraint. Inparticular, ~;5 percent of the human genome consists of conservednon-coding sequences (CNSs). CNSs differ from other genomic sequences intheir nucleotide composition and must play important functional roles,which mostly remain obscure.Results: We investigated relative abundancesof short sequence motifs in all human CNSs present in the human/mousewhole-genome alignments vs. three background sets of sequences: (i)weakly conserved or unconserved non-coding sequences (non-CNSs); (ii)near-promoter sequences (located between nucleotides -500 and -1500,relative to a start of transcription); and (iii) random sequences withthe same nucleotide composition as that of CNSs. When compared tonon-CNSs and near-promoter sequences, CNSs possess an excess of AT-richmotifs, often containing runs of identical nucleotides. In contrast, whencompared to random sequences, CNSs contain an excess of GC-rich motifswhich, however, lack CpG dinucleotides. Thus, abundance of short sequencemotifs in human CNSs, taken as a whole, is mostly determined by theiroverall compositional properties and not by overrepresentation of anyspecific short motifs. These properties are: (i) high AT-content of CNSs,(ii) a tendency, probably due to context-dependent mutation, of A's andT's to clump, (iii) presence of short GC-rich regions, and (iv) avoidanceof CpG contexts, due to their hypermutability. Only a small number ofshort motifs, overrepresented in all human CNSs are similar to bindingsites of transcription factors from the FOX family.Conclusion: Human CNSsas a whole appear to be too broad a class of sequences to possess strongfootprints of any short sequence-specific functions. Such footprintsshould be studied at the level of functional subclasses of CNSs, such asthose which flank genes with a particular pattern of expression. Overallproperties of CNSs are affected by

  8. Sequence-based classification using discriminatory motif feature selection.

    Directory of Open Access Journals (Sweden)

    Hao Xiong

    Full Text Available Most existing methods for sequence-based classification use exhaustive feature generation, employing, for example, all k-mer patterns. The motivation behind such (enumerative approaches is to minimize the potential for overlooking important features. However, there are shortcomings to this strategy. First, practical constraints limit the scope of exhaustive feature generation to patterns of length ≤ k, such that potentially important, longer (> k predictors are not considered. Second, features so generated exhibit strong dependencies, which can complicate understanding of derived classification rules. Third, and most importantly, numerous irrelevant features are created. These concerns can compromise prediction and interpretation. While remedies have been proposed, they tend to be problem-specific and not broadly applicable. Here, we develop a generally applicable methodology, and an attendant software pipeline, that is predicated on discriminatory motif finding. In addition to the traditional training and validation partitions, our framework entails a third level of data partitioning, a discovery partition. A discriminatory motif finder is used on sequences and associated class labels in the discovery partition to yield a (small set of features. These features are then used as inputs to a classifier in the training partition. Finally, performance assessment occurs on the validation partition. Important attributes of our approach are its modularity (any discriminatory motif finder and any classifier can be deployed and its universality (all data, including sequences that are unaligned and/or of unequal length, can be accommodated. We illustrate our approach on two nucleosome occupancy datasets and a protein solubility dataset, previously analyzed using enumerative feature generation. Our method achieves excellent performance results, with and without optimization of classifier tuning parameters. A Python pipeline implementing the approach is

  9. Motif Discovery in Speech: Application to Monitoring Alzheimer's Disease.

    Science.gov (United States)

    Garrard, Peter; Nemes, Vanda; Nikolic, Dragana; Barney, Anna

    2017-01-01

    Perseveration - repetition of words, phrases or questions in speech - is commonly described in Alzheimer's disease (AD). Measuring perseveration is difficult, but may index cognitive performance, aiding diagnosis and disease monitoring. Continuous recording of speech would produce a large quantity of data requiring painstaking manual analysis, and risk violating patients' and others' privacy. A secure record and an automated approach to analysis are required. To record bone-conducted acoustic energy fluctuations from a subject's vocal apparatus using an accelerometer, to describe the recording and analysis stages in detail, and demonstrate that the approach is feasible in AD. Speech-related vibration was captured by an accelerometer, affixed above the temporomandibular joint. Healthy subjects read a script with embedded repetitions. Features were extracted from recorded signals and combined using Principal Component Analysis to obtain a one-dimensional representation of the feature vector. Motif discovery techniques were used to detect repeated segments. The equipment was tested in AD patients to determine device acceptability and recording quality. Comparison with the known location of embedded motifs suggests that, with appropriate parameter tuning, the motif discovery method can detect repetitions. The device was acceptable to patients and produced adequate signal quality in their home environments. We established that continuously recording bone-conducted speech and detecting perseverative patterns were both possible. In future studies we plan to associate the frequency of verbal repetitions with stage, progression and type of dementia. It is possible that the method could contribute to the assessment of disease-modifying treatments. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  10. Recurring sequence-structure motifs in (βα)8-barrel proteins and experimental optimization of a chimeric protein designed based on such motifs.

    Science.gov (United States)

    Wang, Jichao; Zhang, Tongchuan; Liu, Ruicun; Song, Meilin; Wang, Juncheng; Hong, Jiong; Chen, Quan; Liu, Haiyan

    2017-02-01

    An interesting way of generating novel artificial proteins is to combine sequence motifs from natural proteins, mimicking the evolutionary path suggested by natural proteins comprising recurring motifs. We analyzed the βα and αβ modules of TIM barrel proteins by structure alignment-based sequence clustering. A number of preferred motifs were identified. A chimeric TIM was designed by using recurring elements as mutually compatible interfaces. The foldability of the designed TIM protein was then significantly improved by six rounds of directed evolution. The melting temperature has been improved by more than 20°C. A variety of characteristics suggested that the resulting protein is well-folded. Our analysis provided a library of peptide motifs that is potentially useful for different protein engineering studies. The protein engineering strategy of using recurring motifs as interfaces to connect partial natural proteins may be applied to other protein folds. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Redactable signatures for signed CDA Documents.

    Science.gov (United States)

    Wu, Zhen-Yu; Hsueh, Chih-Wen; Tsai, Cheng-Yu; Lai, Feipei; Lee, Hung-Chang; Chung, Yufang

    2012-06-01

    The Clinical Document Architecture, introduced by Health Level Seven, is a XML-based standard intending to specify the encoding, structure, and semantics of clinical documents for exchange. Since the clinical document is in XML form, its authenticity and integrity could be guaranteed by the use of the XML signature published by W3C. While a clinical document wants to conceal some personal or private information, the document needs to be redacted. It makes the signed signature of the original clinical document not be verified. The redactable signature is thus proposed to enable verification for the redacted document. Only a little research does the implementation of the redactable signature, and there still not exists an appropriate scheme for the clinical document. This paper will investigate the existing web-technologies and find a compact and applicable model to implement a suitable redactable signature for the clinical document viewer.

  12. Real time gamma-ray signature identifier

    Science.gov (United States)

    Rowland, Mark [Alamo, CA; Gosnell, Tom B [Moraga, CA; Ham, Cheryl [Livermore, CA; Perkins, Dwight [Livermore, CA; Wong, James [Dublin, CA

    2012-05-15

    A real time gamma-ray signature/source identification method and system using principal components analysis (PCA) for transforming and substantially reducing one or more comprehensive spectral libraries of nuclear materials types and configurations into a corresponding concise representation/signature(s) representing and indexing each individual predetermined spectrum in principal component (PC) space, wherein an unknown gamma-ray signature may be compared against the representative signature to find a match or at least characterize the unknown signature from among all the entries in the library with a single regression or simple projection into the PC space, so as to substantially reduce processing time and computing resources and enable real-time characterization and/or identification.

  13. How curved membranes recruit amphipathic helices and protein anchoring motifs

    DEFF Research Database (Denmark)

    Hatzakis, Nikos; Bhatia, Vikram Kjøller; Larsen, Jannik

    2009-01-01

    Lipids and several specialized proteins are thought to be able to sense the curvature of membranes (MC). Here we used quantitative fluorescence microscopy to measure curvature-selective binding of amphipathic motifs on single liposomes 50-700 nm in diameter. Our results revealed that sensing...... is predominantly mediated by a higher density of binding sites on curved membranes instead of higher affinity. We proposed a model based on curvature-induced defects in lipid packing that related these findings to lipid sorting and accurately predicted the existence of a new ubiquitous class of curvature sensors...

  14. Indonesian Traditional Toys and the Development of Batik Motifs

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    Bagus Indrayana

    2016-06-01

    Full Text Available There is a wide array of traditional toys in Indonesia. In the past, traditional toys played an important role for skill and creativity development of children. Today, the position of traditional toys in the society is displaced by toys from large-scale manufacturers. Given the critical role of traditional toys for children’s motoric and social development, there is a need to develop media that can be used to promote these traditional products and strengthen their position in the public. We propose to use Batik as a way to effectively disseminate and promote traditional toys to the general public. Apart from this, using traditional toys to create new Batik motifs can have an economic value for the producers of Batik, promote Indonesian products and enrich the Indonesian Batik. This study aims to explore the variety of traditional toys, mainly from Klaten and Magelang, in the Central Java province of Indonesia, and use them as the basis for the development of Batik motif creation. This study used Trilogi Keseimbangan (or Harmony Trilogy aesthetic theory analytical approach that explains the creation of craft consists of the following phases: exploration, design, and materialization. The creation method in this study adopts Tiga Tahap Enam Langkah (Three Phases, Six Steps method offered in the theory. The finding in the field found that the traditional toys material used in Klaten and Magelang, mostly made from waste wood, plywood, and zinc. The manufacturing process is done manually by two or three craftsmen using a simple technology. The traditional toys are designed by the artisans mostly, although there may be designs from the clients. In addition, we also found that the traditional toys have never been used as a Batik motif. The traditional toys Batik motif presented in this work is researcher’s design. For the purposes of this study, we first research the variety of traditional toys available in the market today in Indonesia. We look

  15. Genome wide identification of regulatory motifs in Bacillus subtilis

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    Siggia Eric D

    2003-05-01

    Full Text Available Abstract Background To explain the vastly different phenotypes exhibited by the same organism under different conditions, it is essential that we understand how the organism's genes are coordinately regulated. While there are many excellent tools for predicting sequences encoding proteins or RNA genes, few algorithms exist to predict regulatory sequences on a genome wide scale with no prior information. Results To identify motifs involved in the control of transcription, an algorithm was developed that searches upstream of operons for improbably frequent dimers. The algorithm was applied to the B. subtilis genome, which is predicted to encode for approximately 200 DNA binding proteins. The dimers found to be over-represented could be clustered into 317 distinct groups, each thought to represent a class of motifs uniquely recognized by some transcription factor. For each cluster of dimers, a representative weight matrix was derived and scored over the regions upstream of the operons to predict the sites recognized by the cluster's factor, and a putative regulon of the operons immediately downstream of the sites was inferred. The distribution in number of operons per predicted regulon is comparable to that for well characterized transcription factors. The most highly over-represented dimers matched σA, the T-box, and σW sites. We have evidence to suggest that at least 52 of our clusters of dimers represent actual regulatory motifs, based on the groups' weight matrix matches to experimentally characterized sites, the functional similarity of the component operons of the groups' regulons, and the positional biases of the weight matrix matches. All predictions are assigned a significance value, and thresholds are set to avoid false positives. Where possible, we examine our false negatives, drawing examples from known regulatory motifs and regulons inferred from RNA expression data. Conclusions We have demonstrated that in the case of B. subtilis

  16. Dimensionality of social networks using motifs and eigenvalues.

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    Anthony Bonato

    Full Text Available We consider the dimensionality of social networks, and develop experiments aimed at predicting that dimension. We find that a social network model with nodes and links sampled from an m-dimensional metric space with power-law distributed influence regions best fits samples from real-world networks when m scales logarithmically with the number of nodes of the network. This supports a logarithmic dimension hypothesis, and we provide evidence with two different social networks, Facebook and LinkedIn. Further, we employ two different methods for confirming the hypothesis: the first uses the distribution of motif counts, and the second exploits the eigenvalue distribution.

  17. Nucleic Acid i-Motif Structures in Analytical Chemistry.

    Science.gov (United States)

    Alba, Joan Josep; Sadurní, Anna; Gargallo, Raimundo

    2016-09-02

    Under the appropriate experimental conditions of pH and temperature, cytosine-rich segments in DNA or RNA sequences may produce a characteristic folded structure known as an i-motif. Besides its potential role in vivo, which is still under investigation, this structure has attracted increasing interest in other fields due to its sharp, fast and reversible pH-driven conformational changes. This "on/off" switch at molecular level is being used in nanotechnology and analytical chemistry to develop nanomachines and sensors, respectively. This paper presents a review of the latest applications of this structure in the field of chemical analysis.

  18. Recurrent signature patterns in HIV-1 B clade envelope glycoproteins associated with either early or chronic infections.

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    S Gnanakaran

    2011-09-01

    Full Text Available Here we have identified HIV-1 B clade Envelope (Env amino acid signatures from early in infection that may be favored at transmission, as well as patterns of recurrent mutation in chronic infection that may reflect common pathways of immune evasion. To accomplish this, we compared thousands of sequences derived by single genome amplification from several hundred individuals that were sampled either early in infection or were chronically infected. Samples were divided at the outset into hypothesis-forming and validation sets, and we used phylogenetically corrected statistical strategies to identify signatures, systematically scanning all of Env. Signatures included single amino acids, glycosylation motifs, and multi-site patterns based on functional or structural groupings of amino acids. We identified signatures near the CCR5 co-receptor-binding region, near the CD4 binding site, and in the signal peptide and cytoplasmic domain, which may influence Env expression and processing. Two signatures patterns associated with transmission were particularly interesting. The first was the most statistically robust signature, located in position 12 in the signal peptide. The second was the loss of an N-linked glycosylation site at positions 413-415; the presence of this site has been recently found to be associated with escape from potent and broad neutralizing antibodies, consistent with enabling a common pathway for immune escape during chronic infection. Its recurrent loss in early infection suggests it may impact fitness at the time of transmission or during early viral expansion. The signature patterns we identified implicate Env expression levels in selection at viral transmission or in early expansion, and suggest that immune evasion patterns that recur in many individuals during chronic infection when antibodies are present can be selected against when the infection is being established prior to the adaptive immune response.

  19. A fast weak motif-finding algorithm based on community detection in graphs.

    Science.gov (United States)

    Jia, Caiyan; Carson, Matthew B; Yu, Jian

    2013-07-17

    Identification of transcription factor binding sites (also called 'motif discovery') in DNA sequences is a basic step in understanding genetic regulation. Although many successful programs have been developed, the problem is far from being solved on account of diversity in gene expression/regulation and the low specificity of binding sites. State-of-the-art algorithms have their own constraints (e.g., high time or space complexity for finding long motifs, low precision in identification of weak motifs, or the OOPS constraint: one occurrence of the motif instance per sequence) which limit their scope of application. In this paper, we present a novel and fast algorithm we call TFBSGroup. It is based on community detection from a graph and is used to discover long and weak (l,d) motifs under the ZOMOPS constraint (zero, one or multiple occurrence(s) of the motif instance(s) per sequence), where l is the length of a motif and d is the maximum number of mutations between a motif instance and the motif itself. Firstly, TFBSGroup transforms the (l, d) motif search in sequences to focus on the discovery of dense subgraphs within a graph. It identifies these subgraphs using a fast community detection method for obtaining coarse-grained candidate motifs. Next, it greedily refines these candidate motifs towards the true motif within their own communities. Empirical studies on synthetic (l, d) samples have shown that TFBSGroup is very efficient (e.g., it can find true (18, 6), (24, 8) motifs within 30 seconds). More importantly, the algorithm has succeeded in rapidly identifying motifs in a large data set of prokaryotic promoters generated from the Escherichia coli database RegulonDB. The algorithm has also accurately identified motifs in ChIP-seq data sets for 12 mouse transcription factors involved in ES cell pluripotency and self-renewal. Our novel heuristic algorithm, TFBSGroup, is able to quickly identify nearly exact matches for long and weak (l, d) motifs in DNA

  20. Fast and accurate discovery of degenerate linear motifs in protein sequences.

    Science.gov (United States)

    Kelil, Abdellali; Dubreuil, Benjamin; Levy, Emmanuel D; Michnick, Stephen W

    2014-01-01

    Linear motifs mediate a wide variety of cellular functions, which makes their characterization in protein sequences crucial to understanding cellular systems. However, the short length and degenerate nature of linear motifs make their discovery a difficult problem. Here, we introduce MotifHound, an algorithm particularly suited for the discovery of small and degenerate linear motifs. MotifHound performs an exact and exhaustive enumeration of all motifs present in proteins of interest, including all of their degenerate forms, and scores the overrepresentation of each motif based on its occurrence in proteins of interest relative to a background (e.g., proteome) using the hypergeometric distribution. To assess MotifHound, we benchmarked it together with state-of-the-art algorithms. The benchmark consists of 11,880 sets of proteins from S. cerevisiae; in each set, we artificially spiked-in one motif varying in terms of three key parameters, (i) number of occurrences, (ii) length and (iii) the number of degenerate or "wildcard" positions. The benchmark enabled the evaluation of the impact of these three properties on the performance of the different algorithms. The results showed that MotifHound and SLiMFinder were the most accurate in detecting degenerate linear motifs. Interestingly, MotifHound was 15 to 20 times faster at comparable accuracy and performed best in the discovery of highly degenerate motifs. We complemented the benchmark by an analysis of proteins experimentally shown to bind the FUS1 SH3 domain from S. cerevisiae. Using the full-length protein partners as sole information, MotifHound recapitulated most experimentally determined motifs binding to the FUS1 SH3 domain. Moreover, these motifs exhibited properties typical of SH3 binding peptides, e.g., high intrinsic disorder and evolutionary conservation, despite the fact that none of these properties were used as prior information. MotifHound is available (http://michnick.bcm.umontreal.ca or http

  1. HIGEDA: a hierarchical gene-set genetics based algorithm for finding subtle motifs in biological sequences.

    Science.gov (United States)

    Le, Thanh; Altman, Tom; Gardiner, Katheleen

    2010-02-01

    Identification of motifs in biological sequences is a challenging problem because such motifs are often short, degenerate, and may contain gaps. Most algorithms that have been developed for motif-finding use the expectation-maximization (EM) algorithm iteratively. Although EM algorithms can converge quickly, they depend strongly on initialization parameters and can converge to local sub-optimal solutions. In addition, they cannot generate gapped motifs. The effectiveness of EM algorithms in motif finding can be improved by incorporating methods that choose different sets of initial parameters to enable escape from local optima, and that allow gapped alignments within motif models. We have developed HIGEDA, an algorithm that uses the hierarchical gene-set genetic algorithm (HGA) with EM to initiate and search for the best parameters for the motif model. In addition, HIGEDA can identify gapped motifs using a position weight matrix and dynamic programming to generate an optimal gapped alignment of the motif model with sequences from the dataset. We show that HIGEDA outperforms MEME and other motif-finding algorithms on both DNA and protein sequences. Source code and test datasets are available for download at http://ouray.cudenver.edu/~tnle/, implemented in C++ and supported on Linux and MS Windows.

  2. CMD: A Database to Store the Bonding States of Cysteine Motifs with Secondary Structures.

    Science.gov (United States)

    Bostan, Hamed; Salim, Naomie; Hussein, Zeti Azura; Klappa, Peter; Shamsir, Mohd Shahir

    2012-01-01

    Computational approaches to the disulphide bonding state and its connectivity pattern prediction are based on various descriptors. One descriptor is the amino acid sequence motifs flanking the cysteine residue motifs. Despite the existence of disulphide bonding information in many databases and applications, there is no complete reference and motif query available at the moment. Cysteine motif database (CMD) is the first online resource that stores all cysteine residues, their flanking motifs with their secondary structure, and propensity values assignment derived from the laboratory data. We extracted more than 3 million cysteine motifs from PDB and UniProt data, annotated with secondary structure assignment, propensity value assignment, and frequency of occurrence and coefficiency of their bonding status. Removal of redundancies generated 15875 unique flanking motifs that are always bonded and 41577 unique patterns that are always nonbonded. Queries are based on the protein ID, FASTA sequence, sequence motif, and secondary structure individually or in batch format using the provided APIs that allow remote users to query our database via third party software and/or high throughput screening/querying. The CMD offers extensive information about the bonded, free cysteine residues, and their motifs that allows in-depth characterization of the sequence motif composition.

  3. CMD: A Database to Store the Bonding States of Cysteine Motifs with Secondary Structures

    Directory of Open Access Journals (Sweden)

    Hamed Bostan

    2012-01-01

    Full Text Available Computational approaches to the disulphide bonding state and its connectivity pattern prediction are based on various descriptors. One descriptor is the amino acid sequence motifs flanking the cysteine residue motifs. Despite the existence of disulphide bonding information in many databases and applications, there is no complete reference and motif query available at the moment. Cysteine motif database (CMD is the first online resource that stores all cysteine residues, their flanking motifs with their secondary structure, and propensity values assignment derived from the laboratory data. We extracted more than 3 million cysteine motifs from PDB and UniProt data, annotated with secondary structure assignment, propensity value assignment, and frequency of occurrence and coefficiency of their bonding status. Removal of redundancies generated 15875 unique flanking motifs that are always bonded and 41577 unique patterns that are always nonbonded. Queries are based on the protein ID, FASTA sequence, sequence motif, and secondary structure individually or in batch format using the provided APIs that allow remote users to query our database via third party software and/or high throughput screening/querying. The CMD offers extensive information about the bonded, free cysteine residues, and their motifs that allows in-depth characterization of the sequence motif composition.

  4. Finding a Leucine in a Haystack: Searching the Proteome for ambigous Leucine-Aspartic Acid motifs

    KAUST Repository

    Arold, Stefan T.

    2016-01-25

    Leucine-aspartic acid (LD) motifs are short helical protein-protein interaction motifs involved in cell motility, survival and communication. LD motif interactions are also implicated in cancer metastasis and are targeted by several viruses. LD motifs are notoriously difficult to detect because sequence pattern searches lead to an excessively high number of false positives. Hence, despite 20 years of research, only six LD motif–containing proteins are known in humans, three of which are close homologues of the paxillin family. To enable the proteome-wide discovery of LD motifs, we developed LD Motif Finder (LDMF), a web tool based on machine learning that combines sequence information with structural predictions to detect LD motifs with high accuracy. LDMF predicted 13 new LD motifs in humans. Using biophysical assays, we experimentally confirmed in vitro interactions for four novel LD motif proteins. Thus, LDMF allows proteome-wide discovery of LD motifs, despite a highly ambiguous sequence pattern. Functional implications will be discussed.

  5. Motif Discovery in Tissue-Specific Regulatory Sequences Using Directed Information

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    States David

    2007-01-01

    Full Text Available Motif discovery for the identification of functional regulatory elements underlying gene expression is a challenging problem. Sequence inspection often leads to discovery of novel motifs (including transcription factor sites with previously uncharacterized function in gene expression. Coupled with the complexity underlying tissue-specific gene expression, there are several motifs that are putatively responsible for expression in a certain cell type. This has important implications in understanding fundamental biological processes such as development and disease progression. In this work, we present an approach to the identification of motifs (not necessarily transcription factor sites and examine its application to some questions in current bioinformatics research. These motifs are seen to discriminate tissue-specific gene promoter or regulatory regions from those that are not tissue-specific. There are two main contributions of this work. Firstly, we propose the use of directed information for such classification constrained motif discovery, and then use the selected features with a support vector machine (SVM classifier to find the tissue specificity of any sequence of interest. Such analysis yields several novel interesting motifs that merit further experimental characterization. Furthermore, this approach leads to a principled framework for the prospective examination of any chosen motif to be discriminatory motif for a group of coexpressed/coregulated genes, thereby integrating sequence and expression perspectives. We hypothesize that the discovery of these motifs would enable the large-scale investigation for the tissue-specific regulatory role of any conserved sequence element identified from genome-wide studies.

  6. SLiMScape: a protein short linear motif analysis plugin for Cytoscape.

    Science.gov (United States)

    O'Brien, Kevin T; Haslam, Niall J; Shields, Denis C

    2013-07-15

    Computational protein short linear motif discovery can use protein interaction information to search for motifs among proteins which share a common interactor. Cytoscape provides a visual interface for protein networks but there is no streamlined way to rapidly visualize motifs in a network of proteins, or to integrate computational discovery with such visualizations. We present SLiMScape, a Cytoscape plugin, which enables both de novo motif discovery and searches for instances of known motifs. Data is presented using Cytoscape's visualization features thus providing an intuitive interface for interpreting results. The distribution of discovered or user-defined motifs may be selectively displayed and the distribution of protein domains may be viewed simultaneously. To facilitate this SLiMScape automatically retrieves domains for each protein. SLiMScape provides a platform for performing short linear motif analyses of protein interaction networks by integrating motif discovery and search tools in a network visualization environment. This significantly aids in the discovery of novel short linear motifs and in visualizing the distribution of known motifs.

  7. Transduction motif analysis of gastric cancer based on a human signaling network

    Energy Technology Data Exchange (ETDEWEB)

    Liu, G.; Li, D.Z.; Jiang, C.S.; Wang, W. [Fuzhou General Hospital of Nanjing Command, Department of Gastroenterology, Fuzhou, China, Department of Gastroenterology, Fuzhou General Hospital of Nanjing Command, Fuzhou (China)

    2014-04-04

    To investigate signal regulation models of gastric cancer, databases and literature were used to construct the signaling network in humans. Topological characteristics of the network were analyzed by CytoScape. After marking gastric cancer-related genes extracted from the CancerResource, GeneRIF, and COSMIC databases, the FANMOD software was used for the mining of gastric cancer-related motifs in a network with three vertices. The significant motif difference method was adopted to identify significantly different motifs in the normal and cancer states. Finally, we conducted a series of analyses of the significantly different motifs, including gene ontology, function annotation of genes, and model classification. A human signaling network was constructed, with 1643 nodes and 5089 regulating interactions. The network was configured to have the characteristics of other biological networks. There were 57,942 motifs marked with gastric cancer-related genes out of a total of 69,492 motifs, and 264 motifs were selected as significantly different motifs by calculating the significant motif difference (SMD) scores. Genes in significantly different motifs were mainly enriched in functions associated with cancer genesis, such as regulation of cell death, amino acid phosphorylation of proteins, and intracellular signaling cascades. The top five significantly different motifs were mainly cascade and positive feedback types. Almost all genes in the five motifs were cancer related, including EPOR, MAPK14, BCL2L1, KRT18, PTPN6, CASP3, TGFBR2, AR, and CASP7. The development of cancer might be curbed by inhibiting signal transductions upstream and downstream of the selected motifs.

  8. Maximizing biomarker discovery by minimizing gene signatures

    Directory of Open Access Journals (Sweden)

    Chang Chang

    2011-12-01

    Full Text Available Abstract Background The use of gene signatures can potentially be of considerable value in the field of clinical diagnosis. However, gene signatures defined with different methods can be quite various even when applied the same disease and the same endpoint. Previous studies have shown that the correct selection of subsets of genes from microarray data is key for the accurate classification of disease phenotypes, and a number of methods have been proposed for the purpose. However, these methods refine the subsets by only considering each single feature, and they do not confirm the association between the genes identified in each gene signature and the phenotype of the disease. We proposed an innovative new method termed Minimize Feature's Size (MFS based on multiple level similarity analyses and association between the genes and disease for breast cancer endpoints by comparing classifier models generated from the second phase of MicroArray Quality Control (MAQC-II, trying to develop effective meta-analysis strategies to transform the MAQC-II signatures into a robust and reliable set of biomarker for clinical applications. Results We analyzed the similarity of the multiple gene signatures in an endpoint and between the two endpoints of breast cancer at probe and gene levels, the results indicate that disease-related genes can be preferably selected as the components of gene signature, and that the gene signatures for the two endpoints could be interchangeable. The minimized signatures were built at probe level by using MFS for each endpoint. By applying the approach, we generated a much smaller set of gene signature with the similar predictive power compared with those gene signatures from MAQC-II. Conclusions Our results indicate that gene signatures of both large and small sizes could perform equally well in clinical applications. Besides, consistency and biological significances can be detected among different gene signatures, reflecting the

  9. Distinct saturable pathways for the endocytosis of different tyrosine motifs.

    Science.gov (United States)

    Warren, R A; Green, F A; Stenberg, P E; Enns, C A

    1998-07-03

    Endocytosis of surface proteins through clathrin-coated pits requires an internalization signal in the cytoplasmic domain. Two types of internalization signal have been described: one requiring a tyrosine as the critical residue (tyrosine-based motif), and the other consisting of either two consecutive leucines or an isoleucine and leucine (dileucine motif). Although it seems that these signals are necessary and sufficient for endocytic targeting, the mechanism of recognition is not well understood. To examine this question, tetracycline-repressible cell lines were used to overexpress one of several receptors bearing a tyrosine-based internalization signal. By measuring the rates of endocytosis for either the overexpressed receptor, or that of other endogenous receptors, we were able to show that the endocytosis of identical receptors could be saturated, but a complete lack of competition exists between the transferrin receptor (TfR), the low-density lipoprotein receptor, and the epidermal growth factor receptor. Overexpression of any one of these receptors resulted in its redistribution toward the cell surface, implying that entry into coated pits is limited. During high levels of TfR expression, however, a significant increase in the amount of surface Lamp1, but not low-density lipoprotein receptor, epidermal growth factor receptor, or Lamp2, is detected. This suggests that Lamp1 and TfR compete for the same endocytic sites. Together, these results support the idea that there are at least three distinct saturable components involved in clathrin-mediated endocytosis.

  10. PMS6: a fast algorithm for motif discovery.

    Science.gov (United States)

    Bandyopadhyay, Shibdas; Sahni, Sartaj; Rajasekaran, Sanguthevar

    2014-01-01

    We propose a new algorithm, PMS6, for the (l,d)-motif discovery problem in which we are to find all strings of length l that appear in every string of a given set of strings with at most d mismatches. The run time ratio PMS5/PMS6, where PMS5 is the fastest previously known algorithm for motif discovery in large instances, ranges from a high of 2.20 for the (21,8) challenge instances to a low of 1.69 for the (17,6) challenge instances. Both PMS5 and PMS6 require some amount of pre-processing. The pre-processing time for PMS6 is 34 times faster than that for PMS5 for (23,9) instances. When pre-processing time is factored in, the run time ratio PMS5/PMS6 is as high as 2.75 for (13,4) instances and as low as 1.95 for (17,6) instances.

  11. Graph animals, subgraph sampling and motif search in large networks

    CERN Document Server

    Baskerville, Kim; Paczuski, Maya

    2007-01-01

    We generalize a sampling algorithm for lattice animals (connected clusters on a regular lattice) to a Monte Carlo algorithm for `graph animals', i.e. connected subgraphs in arbitrary networks. As with the algorithm in [N. Kashtan et al., Bioinformatics 20, 1746 (2004)], it provides a weighted sample, but the computation of the weights is much faster (linear in the size of subgraphs, instead of super-exponential). This allows subgraphs with up to ten or more nodes to be sampled with very high statistics, from arbitrarily large networks. Using this together with a heuristic algorithm for rapidly classifying isomorphic graphs, we present results for two protein interaction networks obtained using the TAP high throughput method: one of Escherichia coli with 230 nodes and 695 links, and one for yeast (Saccharomyces cerevisiae) with roughly ten times more nodes and links. We find in both cases that most connected subgraphs are strong motifs (Z-scores >10) or anti-motifs (Z-scores <-10) when the null model is the...

  12. Prevalent RNA recognition motif duplication in the human genome.

    Science.gov (United States)

    Tsai, Yihsuan S; Gomez, Shawn M; Wang, Zefeng

    2014-05-01

    The sequence-specific recognition of RNA by proteins is mediated through various RNA binding domains, with the RNA recognition motif (RRM) being the most frequent and present in >50% of RNA-binding proteins (RBPs). Many RBPs contain multiple RRMs, and it is unclear how each RRM contributes to the binding specificity of the entire protein. We found that RRMs within the same RBP (i.e., sibling RRMs) tend to have significantly higher similarity than expected by chance. Sibling RRM pairs from RBPs shared by multiple species tend to have lower similarity than those found only in a single species, suggesting that multiple RRMs within the same protein might arise from domain duplication followed by divergence through random mutations. This finding is exemplified by a recent RRM domain duplication in DAZ proteins and an ancient duplication in PABP proteins. Additionally, we found that different similarities between sibling RRMs are associated with distinct functions of an RBP and that the RBPs tend to contain repetitive sequences with low complexity. Taken together, this study suggests that the number of RBPs with multiple RRMs has expanded in mammals and that the multiple sibling RRMs may recognize similar target motifs in a cooperative manner.

  13. Proline Rich Motifs as Drug Targets in Immune Mediated Disorders

    Directory of Open Access Journals (Sweden)

    Mythily Srinivasan

    2012-01-01

    Full Text Available The current version of the human immunome network consists of nearly 1400 interactions involving approximately 600 proteins. Intermolecular interactions mediated by proline-rich motifs (PRMs are observed in many facets of the immune response. The proline-rich regions are known to preferentially adopt a polyproline type II helical conformation, an extended structure that facilitates transient intermolecular interactions such as signal transduction, antigen recognition, cell-cell communication and cytoskeletal organization. The propensity of both the side chain and the backbone carbonyls of the polyproline type II helix to participate in the interface interaction makes it an excellent recognition motif. An advantage of such distinct chemical features is that the interactions can be discriminatory even in the absence of high affinities. Indeed, the immune response is mediated by well-orchestrated low-affinity short-duration intermolecular interactions. The proline-rich regions are predominantly localized in the solvent-exposed regions such as the loops, intrinsically disordered regions, or between domains that constitute the intermolecular interface. Peptide mimics of the PRM have been suggested as potential antagonists of intermolecular interactions. In this paper, we discuss novel PRM-mediated interactions in the human immunome that potentially serve as attractive targets for immunomodulation and drug development for inflammatory and autoimmune pathologies.

  14. Romanian traditional motif - element of modernity in clothing

    Science.gov (United States)

    Doble, L.; Stan, O.; Suteu, M. D.; Albu, A.; Bohm, G.; Tsatsarou-Michalaki, A.; Gialinou, E.

    2017-10-01

    In this paper are presented the phases for improving from an aesthetic point of view a clothing item, the jacket respectively, with a straight cut for women using software design patterns, computerised graphics and textile different modern technologies including: industrial embroidery, digital printing, sublimation. In the first phase a documentation was prepared in the Ethnographic Museum of Transylvania from Cluj Napoca where more traditional motifs were selected specific to Transylvania etnographic region and were reintepreted and stylized whilst preserving the symbolism and color range specified to the area. For the styling phase was used CorelDraw vector graphics program that allows changing the shape, size and color of the drawings without affecting the identity of the pattern. In the patterns design phase Gemini CAD software was used and for the modeling and model development Optitex software was used. The part for garnishing the model was performed using Embrodery machine software reproducing the stylized motif identically. In order to obtain a significantly improved aesthetic look and an added artistic value the pattern chosen for the jacket was done using a combination of modern textile technologies. This has allowed the realization of a particular texture on the surface of the designed product, demonstrating that traditional patterns can be reintepreted in modern clothing

  15. info-gibbs: a motif discovery algorithm that directly optimizes information content during sampling.

    Science.gov (United States)

    Defrance, Matthieu; van Helden, Jacques

    2009-10-15

    Discovering cis-regulatory elements in genome sequence remains a challenging issue. Several methods rely on the optimization of some target scoring function. The information content (IC) or relative entropy of the motif has proven to be a good estimator of transcription factor DNA binding affinity. However, these information-based metrics are usually used as a posteriori statistics rather than during the motif search process itself. We introduce here info-gibbs, a Gibbs sampling algorithm that efficiently optimizes the IC or the log-likelihood ratio (LLR) of the motif while keeping computation time low. The method compares well with existing methods like MEME, BioProspector, Gibbs or GAME on both synthetic and biological datasets. Our study shows that motif discovery techniques can be enhanced by directly focusing the search on the motif IC or the motif LLR. http://rsat.ulb.ac.be/rsat/info-gibbs

  16. Anion induced conformational preference of CαNN motif residues in functional proteins.

    Science.gov (United States)

    Patra, Piya; Ghosh, Mahua; Banerjee, Raja; Chakrabarti, Jaydeb

    2017-12-01

    Among different ligand binding motifs, anion binding C α NN motif consisting of peptide backbone atoms of three consecutive residues are observed to be important for recognition of free anions, like sulphate or biphosphate and participate in different key functions. Here we study the interaction of sulphate and biphosphate with C α NN motif present in different proteins. Instead of total protein, a peptide fragment has been studied keeping C α NN motif flanked in between other residues. We use classical force field based molecular dynamics simulations to understand the stability of this motif. Our data indicate fluctuations in conformational preferences of the motif residues in absence of the anion. The anion gives stability to one of these conformations. However, the anion induced conformational preferences are highly sequence dependent and specific to the type of anion. In particular, the polar residues are more favourable compared to the other residues for recognising the anion. © 2017 Wiley Periodicals, Inc.

  17. RSAT::Plants: Motif Discovery in ChIP-Seq Peaks of Plant Genomes.

    Science.gov (United States)

    Castro-Mondragon, Jaime A; Rioualen, Claire; Contreras-Moreira, Bruno; van Helden, Jacques

    2016-01-01

    In this protocol, we explain how to run ab initio motif discovery in order to gather putative transcription factor binding motifs (TFBMs) from sets of genomic regions returned by ChIP-seq experiments. The protocol starts from a set of peak coordinates (genomic regions) which can be either downloaded from ChIP-seq databases, or produced by a peak-calling software tool. We provide a concise description of the successive steps to discover motifs, cluster the motifs returned by different motif discovery algorithms, and compare them with reference motif databases. The protocol is documented with detailed notes explaining the rationale underlying the choice of options. The interpretation of the results is illustrated with an example from the model plant Arabidopsis thaliana.

  18. Bilepton signatures at the LHC

    Science.gov (United States)

    Corcella, Gennaro; Corianò, Claudio; Costantini, Antonio; Frampton, Paul H.

    2017-10-01

    We discuss the main signatures of the Bilepton Model at the Large Hadron Collider, focusing on its gauge boson sector. The model is characterised by five additional gauge bosons, four charged and one neutral, beyond those of the Standard Model, plus three exotic quarks. The latter turn into ordinary quarks with the emission of bilepton doublets (Y++ ,Y+) and (Y- ,Y-) of lepton number L = - 2 and L = + 2 respectively, with the doubly-charged bileptons decaying into same-sign lepton pairs. We perform a phenomenological analysis investigating processes with two doubly-charged bileptons and two jets at the LHC and find that, setting suitable cuts on pseudorapidities and transverse momenta of final-states jets and leptons, the model yields a visible signal and the main Standard Model backgrounds can be suppressed. Compared to previous studies, our investigation is based on a full Monte Carlo implementation of the model and accounts for parton showers, hadronization and an actual jet-clustering algorithm for both signal and Standard Model background, thus providing an optimal framework for an actual experimental search.

  19. Epigenetic Signatures of Cigarette Smoking.

    Science.gov (United States)

    Joehanes, Roby; Just, Allan C; Marioni, Riccardo E; Pilling, Luke C; Reynolds, Lindsay M; Mandaviya, Pooja R; Guan, Weihua; Xu, Tao; Elks, Cathy E; Aslibekyan, Stella; Moreno-Macias, Hortensia; Smith, Jennifer A; Brody, Jennifer A; Dhingra, Radhika; Yousefi, Paul; Pankow, James S; Kunze, Sonja; Shah, Sonia H; McRae, Allan F; Lohman, Kurt; Sha, Jin; Absher, Devin M; Ferrucci, Luigi; Zhao, Wei; Demerath, Ellen W; Bressler, Jan; Grove, Megan L; Huan, Tianxiao; Liu, Chunyu; Mendelson, Michael M; Yao, Chen; Kiel, Douglas P; Peters, Annette; Wang-Sattler, Rui; Visscher, Peter M; Wray, Naomi R; Starr, John M; Ding, Jingzhong; Rodriguez, Carlos J; Wareham, Nicholas J; Irvin, Marguerite R; Zhi, Degui; Barrdahl, Myrto; Vineis, Paolo; Ambatipudi, Srikant; Uitterlinden, André G; Hofman, Albert; Schwartz, Joel; Colicino, Elena; Hou, Lifang; Vokonas, Pantel S; Hernandez, Dena G; Singleton, Andrew B; Bandinelli, Stefania; Turner, Stephen T; Ware, Erin B; Smith, Alicia K; Klengel, Torsten; Binder, Elisabeth B; Psaty, Bruce M; Taylor, Kent D; Gharib, Sina A; Swenson, Brenton R; Liang, Liming; DeMeo, Dawn L; O'Connor, George T; Herceg, Zdenko; Ressler, Kerry J; Conneely, Karen N; Sotoodehnia, Nona; Kardia, Sharon L R; Melzer, David; Baccarelli, Andrea A; van Meurs, Joyce B J; Romieu, Isabelle; Arnett, Donna K; Ong, Ken K; Liu, Yongmei; Waldenberger, Melanie; Deary, Ian J; Fornage, Myriam; Levy, Daniel; London, Stephanie J

    2016-10-01

    DNA methylation leaves a long-term signature of smoking exposure and is one potential mechanism by which tobacco exposure predisposes to adverse health outcomes, such as cancers, osteoporosis, lung, and cardiovascular disorders. To comprehensively determine the association between cigarette smoking and DNA methylation, we conducted a meta-analysis of genome-wide DNA methylation assessed using the Illumina BeadChip 450K array on 15 907 blood-derived DNA samples from participants in 16 cohorts (including 2433 current, 6518 former, and 6956 never smokers). Comparing current versus never smokers, 2623 cytosine-phosphate-guanine sites (CpGs), annotated to 1405 genes, were statistically significantly differentially methylated at Bonferroni threshold of Psmoking-related traits in genome-wide studies including pulmonary function, cancers, inflammatory diseases, and heart disease. Comparing former versus never smokers, 185 of the CpGs that differed between current and never smokers were significant Psmoking cessation. Transcriptomic integration identified effects on gene expression at many differentially methylated CpGs. Cigarette smoking has a broad impact on genome-wide methylation that, at many loci, persists many years after smoking cessation. Many of the differentially methylated genes were novel genes with respect to biological effects of smoking and might represent therapeutic targets for prevention or treatment of tobacco-related diseases. Methylation at these sites could also serve as sensitive and stable biomarkers of lifetime exposure to tobacco smoke. © 2016 American Heart Association, Inc.

  20. Metabolomic signature of brain cancer.

    Science.gov (United States)

    Pandey, Renu; Caflisch, Laura; Lodi, Alessia; Brenner, Andrew J; Tiziani, Stefano

    2017-11-01

    Despite advances in surgery and adjuvant therapy, brain tumors represent one of the leading causes of cancer-related mortality and morbidity in both adults and children. Gliomas constitute about 60% of all cerebral tumors, showing varying degrees of malignancy. They are difficult to treat due to dismal prognosis and limited therapeutics. Metabolomics is the untargeted and targeted analyses of endogenous and exogenous small molecules, which charact erizes the phenotype of an individual. This emerging "omics" science provides functional readouts of cellular activity that contribute greatly to the understanding of cancer biology including brain tumor biology. Metabolites are highly informative as a direct signature of biochemical activity; therefore, metabolite profiling has become a promising approach for clinical diagnostics and prognostics. The metabolic alterations are well-recognized as one of the key hallmarks in monitoring disease progression, therapy, and revealing new molecular targets for effective therapeutic intervention. Taking advantage of the latest high-throughput analytical technologies, that is, nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS), metabolomics is now a promising field for precision medicine and drug discovery. In the present report, we review the application of metabolomics and in vivo metabolic profiling in the context of adult gliomas and paediatric brain tumors. Analytical platforms such as high-resolution (HR) NMR, in vivo magnetic resonance spectroscopic imaging and high- and low-resolution MS are discussed. Moreover, the relevance of metabolic studies in the development of new therapeutic strategies for treatment of gliomas are reviewed. © 2017 Wiley Periodicals, Inc.

  1. Reduction of a Ship's Magnetic Field Signatures

    CERN Document Server

    Holmes, John

    2008-01-01

    Decreasing the magnetic field signature of a naval vessel will reduce its susceptibility to detonating naval influence mines and the probability of a submarine being detected by underwater barriers and maritime patrol aircraft. Both passive and active techniques for reducing the magnetic signatures produced by a vessel's ferromagnetism, roll-induced eddy currents, corrosion-related sources, and stray fields are presented. Mathematical models of simple hull shapes are used to predict the levels of signature reduction that might be achieved through the use of alternate construction materials. Al

  2. Coordinated Action of Two Double-Stranded RNA Binding Motifs and an RGG Motif Enables Nuclear Factor 90 To Flexibly Target Different RNA Substrates.

    Science.gov (United States)

    Schmidt, Tobias; Knick, Paul; Lilie, Hauke; Friedrich, Susann; Golbik, Ralph Peter; Behrens, Sven-Erik

    2016-02-16

    The mechanisms of how RNA binding proteins (RBP) bind to and distinguish different RNA molecules are yet uncertain. Here, we performed a comprehensive analysis of the RNA binding properties of multidomain RBP nuclear factor 90 (NF90) by investigating specifically the functional activities of two double-stranded RNA binding motifs (dsRBM) and an RGG motif in the protein's unstructured C-terminus. By comparison of the RNA binding affinities of several NF90 variants and their modes of binding to a set of defined RNA molecules, the activities of the motifs turned out to be very different. While dsRBM1 contributes little to RNA binding, dsRBM2 is essential for effective binding of double-stranded RNA. The protein's immediate C-terminus, including the RGG motif, is indispensable for interactions of the protein with single-stranded RNA, and the RGG motif decisively contributes to NF90's overall RNA binding properties. Conformational studies, which compared wild-type NF90 with a variant that contains a pseudophosphorylated residue in the RGG motif, suggest that the NF90 C-terminus is involved in conformational changes in the protein after RNA binding, with the RGG motif acting as a central regulatory element. In summary, our data propose a concerted action of all RNA binding motifs within the frame of the full-length protein, which may be controlled by regulation of the activity of the RGG motif, e.g., by phosphorylation. This multidomain interplay enables the RBP NF90 to discriminate RNA features by dynamic and adaptable interactions.

  3. NestedMICA as an ab initio protein motif discovery tool

    Directory of Open Access Journals (Sweden)

    Down Thomas A

    2008-01-01

    Full Text Available Abstract Background Discovering overrepresented patterns in amino acid sequences is an important step in protein functional element identification. We adapted and extended NestedMICA, an ab initio motif finder originally developed for finding transcription binding site motifs, to find short protein signals, and compared its performance with another popular protein motif finder, MEME. NestedMICA, an open source protein motif discovery tool written in Java, is driven by a Monte Carlo technique called Nested Sampling. It uses multi-class sequence background models to represent different "uninteresting" parts of sequences that do not contain motifs of interest. In order to assess NestedMICA as a protein motif finder, we have tested it on synthetic datasets produced by spiking instances of known motifs into a randomly selected set of protein sequences. NestedMICA was also tested using a biologically-authentic test set, where we evaluated its performance with respect to varying sequence length. Results Generally NestedMICA recovered most of the short (3–9 amino acid long test protein motifs spiked into a test set of sequences at different frequencies. We showed that it can be used to find multiple motifs at the same time, too. In all the assessment experiments we carried out, its overall motif discovery performance was better than that of MEME. Conclusion NestedMICA proved itself to be a robust and sensitive ab initio protein motif finder, even for relatively short motifs that exist in only a small fraction of sequences. Availability NestedMICA is available under the Lesser GPL open-source license from: http://www.sanger.ac.uk/Software/analysis/nmica/

  4. Vampirism today : the change of the vampire motif from the gothic novel to today's fantasy literature

    OpenAIRE

    Resch, Tina

    2009-01-01

    This thesis examins the change of the vampire motif throughout time. How have vampires and their clichés changed and why? Starting with a brief examination of the 'classical' litarary vampire, I mainly focus on contemporary fantasy literature by discussing recent works of vampire fiction. The adaptation of the vampire motif in role-playing games will as well be discussed as the effects the vampire film had on the motif.

  5. The value of position-specific priors in motif discovery using MEME.

    Science.gov (United States)

    Bailey, Timothy L; Bodén, Mikael; Whitington, Tom; Machanick, Philip

    2010-04-09

    Position-specific priors have been shown to be a flexible and elegant way to extend the power of Gibbs sampler-based motif discovery algorithms. Information of many types-including sequence conservation, nucleosome positioning, and negative examples-can be converted into a prior over the location of motif sites, which then guides the sequence motif discovery algorithm. This approach has been shown to confer many of the benefits of conservation-based and discriminative motif discovery approaches on Gibbs sampler-based motif discovery methods, but has not previously been studied with methods based on expectation maximization (EM). We extend the popular EM-based MEME algorithm to utilize position-specific priors and demonstrate their effectiveness for discovering transcription factor (TF) motifs in yeast and mouse DNA sequences. Utilizing a discriminative, conservation-based prior dramatically improves MEME's ability to discover motifs in 156 yeast TF ChIP-chip datasets, more than doubling the number of datasets where it finds the correct motif. On these datasets, MEME using the prior has a higher success rate than eight other conservation-based motif discovery approaches. We also show that the same type of prior improves the accuracy of motifs discovered by MEME in mouse TF ChIP-seq data, and that the motifs tend to be of slightly higher quality those found by a Gibbs sampling algorithm using the same prior. We conclude that using position-specific priors can substantially increase the power of EM-based motif discovery algorithms such as MEME algorithm.

  6. AMD, an Automated Motif Discovery Tool Using Stepwise Refinement of Gapped Consensuses

    OpenAIRE

    Shi, Jiantao; Yang, Wentao; Chen, Mingjie; Du, Yanzhi; Zhang, Ji; Wang, Kankan

    2011-01-01

    Motif discovery is essential for deciphering regulatory codes from high throughput genomic data, such as those from ChIP-chip/seq experiments. However, there remains a lack of effective and efficient methods for the identification of long and gapped motifs in many relevant tools reported to date. We describe here an automated tool that allows for de novo discovery of transcription factor binding sites, regardless of whether the motifs are long or short, gapped or contiguous.

  7. Hybrid DNA i-motif: Aminoethylprolyl-PNA (pC5) enhance the stability of DNA (dC5) i-motif structure.

    Science.gov (United States)

    Gade, Chandrasekhar Reddy; Sharma, Nagendra K

    2017-12-15

    This report describes the synthesis of C-rich sequence, cytosine pentamer, of aep-PNA and its biophysical studies for the formation of hybrid DNA:aep-PNAi-motif structure with DNA cytosine pentamer (dC 5 ) under acidic pH conditions. Herein, the CD/UV/NMR/ESI-Mass studies strongly support the formation of stable hybrid DNA i-motif structure with aep-PNA even near acidic conditions. Hence aep-PNA C-rich sequence cytosine could be considered as potential DNA i-motif stabilizing agents in vivo conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. A motif extraction algorithm based on hashing and modulo-4 arithmetic.

    Science.gov (United States)

    Sheng, Huitao; Mehrotra, Kishan; Mohan, Chilukuri; Raina, Ramesh

    2008-01-01

    We develop an algorithm to identify cis-elements in promoter regions of coregulated genes. This algorithm searches for subsequences of desired length whose frequency of occurrence is relatively high, while accounting for slightly perturbed variants using hash table and modulo arithmetic. Motifs are evaluated using profile matrices and higher-order Markov background model. Simulation results show that our algorithm discovers more motifs present in the test sequences, when compared with two well-known motif-discovery tools (MDScan and AlignACE). The algorithm produces very promising results on real data set; the output of the algorithm contained many known motifs.

  9. Mapping network motif tunability and robustness in the design of synthetic signaling circuits.

    Directory of Open Access Journals (Sweden)

    Sergio Iadevaia

    Full Text Available Cellular networks are highly dynamic in their function, yet evolutionarily conserved in their core network motifs or topologies. Understanding functional tunability and robustness of network motifs to small perturbations in function and structure is vital to our ability to synthesize controllable circuits. In establishing core sets of network motifs, we selected topologies that are overrepresented in mammalian networks, including the linear, feedback, feed-forward, and bifan circuits. Static and dynamic tunability of network motifs were defined as the motif ability to respectively attain steady-state or transient outputs in response to pre-defined input stimuli. Detailed computational analysis suggested that static tunability is insensitive to the circuit topology, since all of the motifs displayed similar ability to attain predefined steady-state outputs in response to constant inputs. Dynamic tunability, in contrast, was tightly dependent on circuit topology, with some motifs performing superiorly in achieving observed time-course outputs. Finally, we mapped dynamic tunability onto motif topologies to determine robustness of motif structures to changes in topology and identify design principles for the rational assembly of robust synthetic networks.

  10. Analysis of genomic sequence motifs for deciphering transcription factor binding and transcriptional regulation in eukaryotic cells

    Directory of Open Access Journals (Sweden)

    Valentina eBoeva

    2016-02-01

    Full Text Available Eukaryotic genomes contain a variety of structured patterns: repetitive elements, binding sites of DNA and RNA associated proteins, splice sites and so on. Often, these structured patterns can be formalized as motifs and described using a proper mathematical model such as position weight matrix and IUPAC consensus. Two key tasks are typically carried out for motifs in the context of the analysis of genomic sequences. These are: identification in a set of DNA regions of over-represented motifs from a particular motif database, and de novo discovery of over-represented motifs. Here we describe existing methodology to perform these two tasks for motifs characterizing transcription factor binding. When applied to the output of ChIP-seq and ChIP-exo experiments, or to promoter regions of co-modulated genes, motif analysis techniques allow for the prediction of transcription factor binding events and enable identification of transcriptional regulators and co-regulators. The usefulness of motif analysis is further exemplified in this review by how motif discovery improves peak calling in ChIP-seq and ChIP-exo experiments and, when coupled with information on gene expression, allows insights into physical mechanisms of transcriptional modulation.

  11. Combining intrinsic disorder prediction and augmented training of hidden Markov models improves discriminative motif discovery

    Science.gov (United States)

    Song, Tao; Bu, Xiaoting; Gu, Hong

    2015-08-01

    Identifying short linear motifs (SLiMs) usually suffers from lack of sufficient sequences. SLiMs with the same functional site class are typically characterized by similar motif patterns, which makes them hard to distinguish by generative motif discovery methods. A discriminative method based on maximal mutual information estimation (MMIE) of hidden Markov models (HMMs) is proposed. It masks ordered regions to improve signal to noise ratio and augments the training set to diminish the impact of the lack of sequences. Experimental results on a dataset selected from the Eukaryotic Linear Motif (ELM) resource show that the proposed method is effective and practical.

  12. A general approach for discriminative de novo motif discovery from high-throughput data.

    Science.gov (United States)

    Grau, Jan; Posch, Stefan; Grosse, Ivo; Keilwagen, Jens

    2013-11-01

    De novo motif discovery has been an important challenge of bioinformatics for the past two decades. Since the emergence of high-throughput techniques like ChIP-seq, ChIP-exo and protein-binding microarrays (PBMs), the focus of de novo motif discovery has shifted to runtime and accuracy on large data sets. For this purpose, specialized algorithms have been designed for discovering motifs in ChIP-seq or PBM data. However, none of the existing approaches work perfectly for all three high-throughput techniques. In this article, we propose Dimont, a general approach for fast and accurate de novo motif discovery from high-throughput data. We demonstrate that Dimont yields a higher number of correct motifs from ChIP-seq data than any of the specialized approaches and achieves a higher accuracy for predicting PBM intensities from probe sequence than any of the approaches specifically designed for that purpose. Dimont also reports the expected motifs for several ChIP-exo data sets. Investigating differences between in vitro and in vivo binding, we find that for most transcription factors, the motifs discovered by Dimont are in good accordance between techniques, but we also find notable exceptions. We also observe that modeling intra-motif dependencies may increase accuracy, which indicates that more complex motif models are a worthwhile field of research.

  13. A review on models and algorithms for motif discovery in protein-protein interaction networks.

    Science.gov (United States)

    Ciriello, Giovanni; Guerra, Concettina

    2008-03-01

    Several algorithms have been recently designed to identify motifs in biological networks, particularly in protein-protein interaction networks. Motifs correspond to repeated modules in the network that may be of biological interest. The approaches proposed in the literature often differ in the definition of a motif, the way the occurrences of a motif are counted and the way their statistical significance is assessed. This has strong implications on the computational complexity of the discovery process and on the type of results that can be expected. This review presents in a systematic way the different computational settings outlining their main features and limitations.

  14. Blind Quantum Signature with Blind Quantum Computation

    Science.gov (United States)

    Li, Wei; Shi, Ronghua; Guo, Ying

    2017-04-01

    Blind quantum computation allows a client without quantum abilities to interact with a quantum server to perform a unconditional secure computing protocol, while protecting client's privacy. Motivated by confidentiality of blind quantum computation, a blind quantum signature scheme is designed with laconic structure. Different from the traditional signature schemes, the signing and verifying operations are performed through measurement-based quantum computation. Inputs of blind quantum computation are securely controlled with multi-qubit entangled states. The unique signature of the transmitted message is generated by the signer without leaking information in imperfect channels. Whereas, the receiver can verify the validity of the signature using the quantum matching algorithm. The security is guaranteed by entanglement of quantum system for blind quantum computation. It provides a potential practical application for e-commerce in the cloud computing and first-generation quantum computation.

  15. Electronic Signatures for Public Procurement across Europe

    Science.gov (United States)

    Ølnes, Jon; Andresen, Anette; Arbia, Stefano; Ernst, Markus; Hagen, Martin; Klein, Stephan; Manca, Giovanni; Rossi, Adriano; Schipplick, Frank; Tatti, Daniele; Wessolowski, Gesa; Windheuser, Jan

    The PEPPOL (Pan-European Public Procurement On-Line) project is a large scale pilot under the CIP programme of the EU, exploring electronic public procurement in a unified European market. An important element is interoperability of electronic signatures across borders, identified today as a major obstacle to cross-border procurement. PEPPOL will address use of signatures in procurement processes, in particular tendering but also post-award processes like orders and invoices. Signature policies, i.e. quality requirements and requirements on information captured in the signing process, will be developed. This as well as technical interoperability of e-signatures across Europe will finally be piloted in demonstrators starting late 2009 or early 2010.

  16. Magnetic Signature of Brushless Electric Motors

    National Research Council Canada - National Science Library

    Clarke, David

    2006-01-01

    Brushless electric motors are used in a number of underwater vehicles. When these underwater vehicles are used for mine clearance operations the magnetic signature of the brushless motors is important...

  17. Sulfur-induced structural motifs on copper and gold surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Walen, Holly [Iowa State Univ., Ames, IA (United States)

    2016-01-01

    The interaction of sulfur with copper and gold surfaces plays a fundamental role in important phenomena that include coarsening of surface nanostructures, and self-assembly of alkanethiols. Here, we identify and analyze unique sulfur-induced structural motifs observed on the low-index surfaces of these two metals. We seek out these structures in an effort to better understand the fundamental interactions between these metals and sulfur that lends to the stability and favorability of metal-sulfur complexes vs. chemisorbed atomic sulfur. The experimental observations presented here—made under identical conditions—together with extensive DFT analyses, allow comparisons and insights into factors that favor the existence of metal-sulfur complexes, vs. chemisorbed atomic sulfur, on metal terraces. We believe this data will be instrumental in better understanding the complex phenomena occurring between the surfaces of coinage metals and sulfur.

  18. Study on online community user motif using web usage mining

    Science.gov (United States)

    Alphy, Meera; Sharma, Ajay

    2016-04-01

    The Web usage mining is the application of data mining, which is used to extract useful information from the online community. The World Wide Web contains at least 4.73 billion pages according to Indexed Web and it contains at least 228.52 million pages according Dutch Indexed web on 6th august 2015, Thursday. It’s difficult to get needed data from these billions of web pages in World Wide Web. Here is the importance of web usage mining. Personalizing the search engine helps the web user to identify the most used data in an easy way. It reduces the time consumption; automatic site search and automatic restore the useful sites. This study represents the old techniques to latest techniques used in pattern discovery and analysis in web usage mining from 1996 to 2015. Analyzing user motif helps in the improvement of business, e-commerce, personalisation and improvement of websites.

  19. Lifetimes and lengthscales of structural motifs in a model glassformer.

    Science.gov (United States)

    Malins, Alex; Eggers, Jens; Tanaka, Hajime; Royall, C Patrick

    2013-01-01

    We use a newly-developed method to identify local structural motifs in a popular model glassformer, the Kob-Andersen binary Lennard-Jones mixture. By measuring the lifetimes of a zoo of clusters, we find that 11-membered bicapped square antiprisms, denoted as 11A, have longer lifetimes on average than other structures considered. Other long-lived clusters are similar in structure to the 11A cluster. These clusters group into ramified networks that are correlated with slow particles and act to retard the motion of neighbouring particles. The structural lengthscale associated with these networks does not grow as fast as the dynamical lengthscale xi(4) as the system is cooled, in the range of temperatures our molecular dynamics simulations access. Thus we find a strong, but indirect, correlation between static structural ordering and slow dynamics.

  20. The postprocessing of quantum digital signatures

    Science.gov (United States)

    Wang, Tian-Yin; Ma, Jian-Feng; Cai, Xiao-Qiu

    2017-01-01

    Many novel quantum digital signature proposals have been proposed, which can effectively guarantee the information-theoretic security of the signature for a singe bit against forging and denying. Using the current basic building blocks of signing a single bit, we give a new proposal to construct an entire protocol for signing a long message. Compared with the previous work, it can improve at least 33.33% efficiency.

  1. Signature for the shape of the universe

    Energy Technology Data Exchange (ETDEWEB)

    Gomero, G.I.; Reboucas, M.J.; Teixeira, A.F.F. [Centro Brasileiro de Pesquisas Fisicas (CBPF), Rio de Janeiro, RJ (Brazil)]. E-mail: german@cbpf.br; reboucas@cbpf.br; teixeira@cbpf.br

    2001-03-01

    If the universe has a nontrival shape (topology) the sky may show multiple correlated images of cosmic objects. These correlations can be counched in terms of distance correlations. We propose a statistical quantity which can be used to reveal the topological signature of any Roberston-Walker (RW) spacetime with nontrivial topology. We also show through computer-aided simulations how one can extract the topological signatures of flat elliptic and hyperbolic RW universes with nontrivial topology. (author)

  2. Quantum blind signature with an offline repository

    Science.gov (United States)

    Ribeiro, J.; Souto, A.; Mateus, P.

    2015-04-01

    We propose a quantum blind signature scheme that achieves perfect security under the assumption of an honest offline repository. The security of the protocol also relies on perfect private quantum channels, which are achievable using quantum one-time pads with keys shared via a quantum key distribution (QKD) protocol. The proposed approach ensures that signatures cannot be copied and that the sender must compromise to a single message, which are important advantages over classical protocols for certain applications.

  3. Signature-based store checking buffer

    Science.gov (United States)

    Sridharan, Vilas; Gurumurthi, Sudhanva

    2015-06-02

    A system and method for optimizing redundant output verification, are provided. A hardware-based store fingerprint buffer receives multiple instances of output from multiple instances of computation. The store fingerprint buffer generates a signature from the content included in the multiple instances of output. When a barrier is reached, the store fingerprint buffer uses the signature to verify the content is error-free.

  4. BIMBINGAN KELUARGA DALAM MEMBANTU ANAK AUTIS (KEHEBATAN MOTIF KEIBUAN

    Directory of Open Access Journals (Sweden)

    Farida Farida

    2015-01-01

    Full Text Available Tulisan ini menjelaskan tentang pola bimbingan yang dilakukan oleh keluarga.  karena tidak bisa dipungkiri anak-anak kenal pertama kali dengan kedua orang tuanya dan mengalami tumbuh kembang dalam lingkungan  keluarga. Keluarga  adalah tempat pertama dan utama untuk tumbuh dan kembang anak (baik anak normal maupun anak berkebutuhan khusus, misalnya autis. Ciri utama anak autis adalah mengalami gangguan komunikasi dan interaksi sosial. Hasilnya upaya orang tua, khususnya ibu (dengan motif keibuan yang dimiliki dalam memberikan bimbingan pada anak autis dengan pembiasaan perilaku baik sampai pemahaman perilaku, penyesuaian perilaku secara keumuman/kelaziman  dan dukungan keluarga akan membantu anak autis untuk tumbuh secara optimal, bahkan meraih prestasi yang sama atau bahkan melebihi anak-anak normal,   seperti  yang  dialami Stephen Wiltshire.   Kata Kunci: Bimbingan Keluarga, Anak Autis, Motif Keibuan. FAMILY     COUNSELLING   IN    HELPING   CHILDREN AUTIS (THE     EXCELLENCE   OF     THE    MOTIF     OF MOTHERHOOD.The first time children know with both parents and experiencing growth and development in a family environment. The family is first and foremost a place for growth and development of children (both normal children and children with special needs, such as autism. The main characteristic of children with autism  is impaired  social interaction  and communication. So that the efforts of parents, especially mothers (the motherhood of motive owned in providing guidance in autistic children by habituation good behavior to understanding  behavior, behavioral  adjustment  in generality  / prevalence  and family  support  will help autistic children to grow optimally, even achievements, equal or even exceed normal kids, like that of Stephen Wiltshire.   Keywords:  Family Guidance, Autistic, Motherhood Motive.

  5. Geochemical and Sulfur-Isotopic Signatures of Volcanogenic Massive Sulfide Deposits on Prince of Wales Island and Vicinity, Southeastern Alaska

    Science.gov (United States)

    Slack, John F.; Shanks, Wayne C.; Karl, Susan M.; Gemery, Pamela A.; Bittenbender, Peter E.; Ridley, W. Ian

    2007-01-01

    example, Mn, As, Sb, and Tl in pyrite from the Moira Sound unit), whereas in other samples the signatures are varyingly annealed, owing to metamorphic overprinting. A limited LA-ICP-MS database for sphalerite indicates that low-Fe sphalerite is preferentially associated with the most Au rich deposits, the Niblack and Nutkwa. Sulfur-isotopic values for sulfide minerals in the VMS deposits in the Wales Group range from 5.9 to 17.4 permil (avg 11.5?2.7 permil), about 5 to 6 permil higher than those in the Moira Sound unit, which range from -2.8 to 10.4 permil (avg 6.1?4.0 permil). This difference in 34Ssulfide values reflects a dominantly seawater sulfate source of the sulfides and is linked to the 34S values of contemporaneous seawater sulfate, which were slightly higher during the Late Proterozoic through Cambrian than during the Ordovician through Early Silurian.

  6. Peripheral Blood Signatures of Lead Exposure

    Science.gov (United States)

    LaBreche, Heather G.; Meadows, Sarah K.; Nevins, Joseph R.; Chute, John P.

    2011-01-01

    Background Current evidence indicates that even low-level lead (Pb) exposure can have detrimental effects, especially in children. We tested the hypothesis that Pb exposure alters gene expression patterns in peripheral blood cells and that these changes reflect dose-specific alterations in the activity of particular pathways. Methodology/Principal Finding Using Affymetrix Mouse Genome 430 2.0 arrays, we examined gene expression changes in the peripheral blood of female Balb/c mice following exposure to per os lead acetate trihydrate or plain drinking water for two weeks and after a two-week recovery period. Data sets were RMA-normalized and dose-specific signatures were generated using established methods of supervised classification and binary regression. Pathway activity was analyzed using the ScoreSignatures module from GenePattern. Conclusions/Significance The low-level Pb signature was 93% sensitive and 100% specific in classifying samples a leave-one-out crossvalidation. The high-level Pb signature demonstrated 100% sensitivity and specificity in the leave-one-out crossvalidation. These two signatures exhibited dose-specificity in their ability to predict Pb exposure and had little overlap in terms of constituent genes. The signatures also seemed to reflect current levels of Pb exposure rather than past exposure. Finally, the two doses showed differential activation of cellular pathways. Low-level Pb exposure increased activity of the interferon-gamma pathway, whereas high-level Pb exposure increased activity of the E2F1 pathway. PMID:21829687

  7. Identifying Discriminating Network Motifs in YouTube Spam

    OpenAIRE

    O'Callaghan, Derek; Harrigan, Martin; Carthy, Joe; Cunningham, Pádraig

    2012-01-01

    Like other social media websites, YouTube is not immune from the attention of spammers. In particular, evidence can be found of attempts to attract users to malicious third-party websites. As this type of spam is often associated with orchestrated campaigns, it has a discernible network signature, based on networks derived from comments posted by users to videos. In this paper, we examine examples of different YouTube spam campaigns of this nature, and use a feature selection process to ident...

  8. Structural fragment clustering reveals novel structural and functional motifs in α-helical transmembrane proteins

    Directory of Open Access Journals (Sweden)

    Vassilev Boris

    2010-04-01

    Full Text Available Abstract Background A large proportion of an organism's genome encodes for membrane proteins. Membrane proteins are important for many cellular processes, and several diseases can be linked to mutations in them. With the tremendous growth of sequence data, there is an increasing need to reliably identify membrane proteins from sequence, to functionally annotate them, and to correctly predict their topology. Results We introduce a technique called structural fragment clustering, which learns sequential motifs from 3D structural fragments. From over 500,000 fragments, we obtain 213 statistically significant, non-redundant, and novel motifs that are highly specific to α-helical transmembrane proteins. From these 213 motifs, 58 of them were assigned to function and checked in the scientific literature for a biological assessment. Seventy percent of the motifs are found in co-factor, ligand, and ion binding sites, 30% at protein interaction interfaces, and 12% bind specific lipids such as glycerol or cardiolipins. The vast majority of motifs (94% appear across evolutionarily unrelated families, highlighting the modularity of functional design in membrane proteins. We describe three novel motifs in detail: (1 a dimer interface motif found in voltage-gated chloride channels, (2 a proton transfer motif found in heme-copper oxidases, and (3 a convergently evolved interface helix motif found in an aspartate symporter, a serine protease, and cytochrome b. Conclusions Our findings suggest that functional modules exist in membrane proteins, and that they occur in completely different evolutionary contexts and cover different binding sites. Structural fragment clustering allows us to link sequence motifs to function through clusters of structural fragments. The sequence motifs can be applied to identify and characterize membrane proteins in novel genomes.

  9. Prediction of virus-host protein-protein interactions mediated by short linear motifs.

    Science.gov (United States)

    Becerra, Andrés; Bucheli, Victor A; Moreno, Pedro A

    2017-03-09

    Short linear motifs in host organisms proteins can be mimicked by viruses to create protein-protein interactions that disable or control metabolic pathways. Given that viral linear motif instances of host motif regular expressions can be found by chance, it is necessary to develop filtering methods of functional linear motifs. We conduct a systematic comparison of linear motifs filtering methods to develop a computational approach for predicting motif-mediated protein-protein interactions between human and the human immunodeficiency virus 1 (HIV-1). We implemented three filtering methods to obtain linear motif sets: 1) conserved in viral proteins (C), 2) located in disordered regions (D) and 3) rare or scarce in a set of randomized viral sequences (R). The sets C,D,R are united and intersected. The resulting sets are compared by the number of protein-protein interactions correctly inferred with them - with experimental validation. The comparison is done with HIV-1 sequences and interactions from the National Institute of Allergy and Infectious Diseases (NIAID). The number of correctly inferred interactions allows to rank the interactions by the sets used to deduce them: D∪R and C. The ordering of the sets is descending on the probability of capturing functional interactions. With respect to HIV-1, the sets C∪R, D∪R, C∪D∪R infer all known interactions between HIV1 and human proteins mediated by linear motifs. We found that the majority of conserved linear motifs in the virus are located in disordered regions. We have developed a method for predicting protein-protein interactions mediated by linear motifs between HIV-1 and human proteins. The method only use protein sequences as inputs. We can extend the software developed to any other eukaryotic virus and host in order to find and rank candidate interactions. In future works we will use it to explore possible viral attack mechanisms based on linear motif mimicry.

  10. Identification of coupling DNA motif pairs on long-range chromatin interactions in human K562 cells

    KAUST Repository

    Wong, Ka-Chun

    2015-09-27

    Motivation: The protein-DNA interactions between transcription factors (TFs) and transcription factor binding sites (TFBSs, also known as DNA motifs) are critical activities in gene transcription. The identification of the DNA motifs is a vital task for downstream analysis. Unfortunately, the long-range coupling information between different DNA motifs is still lacking. To fill the void, as the first-of-its-kind study, we have identified the coupling DNA motif pairs on long-range chromatin interactions in human. Results: The coupling DNA motif pairs exhibit substantially higher DNase accessibility than the background sequences. Half of the DNA motifs involved are matched to the existing motif databases, although nearly all of them are enriched with at least one gene ontology term. Their motif instances are also found statistically enriched on the promoter and enhancer regions. Especially, we introduce a novel measurement called motif pairing multiplicity which is defined as the number of motifs that are paired with a given motif on chromatin interactions. Interestingly, we observe that motif pairing multiplicity is linked to several characteristics such as regulatory region type, motif sequence degeneracy, DNase accessibility and pairing genomic distance. Taken into account together, we believe the coupling DNA motif pairs identified in this study can shed lights on the gene transcription mechanism under long-range chromatin interactions. © The Author 2015. Published by Oxford University Press.

  11. DNase footprint signatures are dictated by factor dynamics and DNA sequence.

    Science.gov (United States)

    Sung, Myong-Hee; Guertin, Michael J; Baek, Songjoon; Hager, Gordon L

    2014-10-23

    Genomic footprinting has emerged as an unbiased discovery method for transcription factor (TF) occupancy at cognate DNA in vivo. A basic premise of footprinting is that sequence-specific TF-DNA interactions are associated with localized resistance to nucleases, leaving observable signatures of cleavage within accessible chromatin. This phenomenon is interpreted to imply protection of the critical nucleotides by the stably bound protein factor. However, this model conflicts with previous reports of many TFs exchanging with specific binding sites in living cells on a timescale of seconds. We show that TFs with short DNA residence times have no footprints at bound motif elements. Moreover, the nuclease cleavage profile within a footprint originates from the DNA sequence in the factor-binding site, rather than from the protein occupying specific nucleotides. These findings suggest a revised understanding of TF footprinting and reveal limitations in comprehensive reconstruction of the TF regulatory network using this approach.

  12. An efficient modified Elliptic Curve Digital Signature Algorithm | Kiros ...

    African Journals Online (AJOL)

    Many digital signatures which are based on Elliptic Curves Cryptography (ECC) have been proposed. Among these digital signatures, the Elliptic Curve Digital Signature Algorithm (ECDSA) is the widely standardized one. However, the verification process of ECDSA is slower than the signature generation process. Hence ...

  13. 21 CFR 11.70 - Signature/record linking.

    Science.gov (United States)

    2010-04-01

    ... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ELECTRONIC RECORDS; ELECTRONIC SIGNATURES Electronic Records § 11.70 Signature/record linking. Electronic signatures and handwritten signatures executed to electronic records shall be linked to their respective...

  14. I-motif structures formed in the human c-MYC promoter are highly dynamic--insights into sequence redundancy and I-motif stability.

    Directory of Open Access Journals (Sweden)

    Jixun Dai

    Full Text Available The GC-rich nuclease hypersensitivity element III1 (NHE III1 of the c-MYC promoter largely controls the transcriptional activity of the c-MYC oncogene. The C-rich strand in this region can form I-motif DNA secondary structures. We determined the folding pattern of the major I-motif formed in the NHE III1, which can be formed at near-neutral pH. While we find that the I-motif formed in the four 3' consecutive runs of cytosines appears to be the most favored, our results demonstrate that the C-rich strand of the c-MYC NHE III1 exhibits a high degree of dynamic equilibration. Using a trisubstituted oligomer of this region, we determined the formation of two equilibrating loop isomers, one of which contains a flipped-out cytosine. Our results indicate that the intercalative cytosine+-cytosine base pairs are not always necessary for an intramolecular I-motif. The dynamic character of the c-MYC I-motif is intrinsic to the NHE III1 sequence and appears to provide stability to the c-MYC I-motif.

  15. Composite Structural Motifs of Binding Sites for Delineating Biological Functions of Proteins

    Science.gov (United States)

    Kinjo, Akira R.; Nakamura, Haruki

    2012-01-01

    Most biological processes are described as a series of interactions between proteins and other molecules, and interactions are in turn described in terms of atomic structures. To annotate protein functions as sets of interaction states at atomic resolution, and thereby to better understand the relation between protein interactions and biological functions, we conducted exhaustive all-against-all atomic structure comparisons of all known binding sites for ligands including small molecules, proteins and nucleic acids, and identified recurring elementary motifs. By integrating the elementary motifs associated with each subunit, we defined composite motifs that represent context-dependent combinations of elementary motifs. It is demonstrated that function similarity can be better inferred from composite motif similarity compared to the similarity of protein sequences or of individual binding sites. By integrating the composite motifs associated with each protein function, we define meta-composite motifs each of which is regarded as a time-independent diagrammatic representation of a biological process. It is shown that meta-composite motifs provide richer annotations of biological processes than sequence clusters. The present results serve as a basis for bridging atomic structures to higher-order biological phenomena by classification and integration of binding site structures. PMID:22347478

  16. SLIDER: A Generic Metaheuristic for the Discovery of Correlated Motifs in Protein-Protein Interaction Networks

    NARCIS (Netherlands)

    Boyen, P.; Dyck, van D.; Neven, F.; Ham, van R.C.H.J.; Dijk, van A.D.J.

    2011-01-01

    Correlated motif mining (CMM) is the problem of finding overrepresented pairs of patterns, called motifs, in sequences of interacting proteins. Algorithmic solutions for CMM thereby provide a computational method for predicting binding sites for protein interaction. In this paper, we adopt a

  17. Endocytic sorting motif interactions involved in Nef-mediated downmodulation of CD4 and CD3.

    Science.gov (United States)

    Manrique, Santiago; Sauter, Daniel; Horenkamp, Florian A; Lülf, Sebastian; Yu, Hangxing; Hotter, Dominik; Anand, Kanchan; Kirchhoff, Frank; Geyer, Matthias

    2017-09-05

    Lentiviral Nefs recruit assembly polypeptide complexes and target sorting motifs in cellular receptors to induce their internalization. While Nef-mediated CD4 downmodulation is conserved, the ability to internalize CD3 was lost in HIV-1 and its precursors. Although both functions play key roles in lentiviral replication and pathogenicity, the underlying structural requirements are poorly defined. Here, we determine the structure of SIVmac239 Nef bound to the ExxxLM motif of another Nef molecule at 2.5 Å resolution. This provides a basis for a structural model, where a hydrophobic crevice in simian immunodeficiency virus (SIV) Nef targets a dileucine motif in CD4 and a tyrosine-based motif in CD3. Introducing key residues into this crevice of HIV-1 Nef enables CD3 binding but an additional N-terminal tyrosine motif is required for internalization. Our resolution of the CD4/Nef/AP2 complex and generation of HIV-1 Nefs capable of CD3 downregulation provide insights into sorting motif interactions and target discrimination of Nef.HIV and simian immunodeficiency virus (SIV) Nef proteins both stimulate the clathrin-mediated endocytosis of CD4 but differ in downmodulation of the immune receptor CD3. Here, the authors present the structure of SIV Nef bound to the ExxxLM motif of another Nef molecule, which allows them to propose a model how Nef recognizes these motifs in CD3 and CD4.

  18. Gene Isolation Using Degenerate Primers Targeting Protein Motif: A Laboratory Exercise

    Science.gov (United States)

    Yeo, Brandon Pei Hui; Foong, Lian Chee; Tam, Sheh May; Lee, Vivian; Hwang, Siaw San

    2018-01-01

    Structures and functions of protein motifs are widely included in many biology-based course syllabi. However, little emphasis is placed to link this knowledge to applications in biotechnology to enhance the learning experience. Here, the conserved motifs of nucleotide binding site-leucine rich repeats (NBS-LRR) proteins, successfully used for the…

  19. Mechanism for activation of the growth factor-activated AGC kinases by turn motif phosphorylation

    DEFF Research Database (Denmark)

    Hauge, Camilla; Antal, Torben L; Hirschberg, Daniel

    2007-01-01

    investigated the role of the third, so-called turn motif phosphate, also located in the tail, in the AGC kinases PKB, S6K, RSK, MSK, PRK and PKC. We report cooperative action of the HM phosphate and the turn motif phosphate, because it binds a phosphoSer/Thr-binding site above the glycine-rich loop within...

  20. Exploring comprehensive within-motif dependence of transcription factor binding in Escherichia coli.

    Science.gov (United States)

    Yang, Chi; Chang, Chuan-Hsiung

    2015-11-23

    Modeling the binding of transcription factors helps to decipher the control logic behind transcriptional regulatory networks. Position weight matrix is commonly used to describe a binding motif but assumes statistical independence between positions. Although current approaches take within-motif dependence into account for better predictive performance, these models usually rely on prior knowledge and incorporate simple positional dependence to describe binding motifs. The inability to take complex within-motif dependence into account may result in an incomplete representation of binding motifs. In this work, we applied association rule mining techniques and constructed models to explore within-motif dependence for transcription factors in Escherichia coli. Our models can reflect transcription factor-DNA recognition where the explored dependence correlates with the binding specificity. We also propose a graphical representation of the explored within-motif dependence to illustrate the final binding configurations. Understanding the binding configurations also enables us to fine-tune or design transcription factor binding sites, and we attempt to present the configurations through exploring within-motif dependence.

  1. An Efficient Exact Algorithm for the Motif Stem Search Problem over Large Alphabets.

    Science.gov (United States)

    Yu, Qiang; Huo, Hongwei; Vitter, Jeffrey Scott; Huan, Jun; Nekrich, Yakov

    2015-01-01

    In recent years, there has been an increasing interest in planted (l, d) motif search (PMS) with applications to discovering significant segments in biological sequences. However, there has been little discussion about PMS over large alphabets. This paper focuses on motif stem search (MSS), which is recently introduced to search motifs on large-alphabet inputs. A motif stem is an l-length string with some wildcards. The goal of the MSS problem is to find a set of stems that represents a superset of all (l , d) motifs present in the input sequences, and the superset is expected to be as small as possible. The three main contributions of this paper are as follows: (1) We build motif stem representation more precisely by using regular expressions. (2) We give a method for generating all possible motif stems without redundant wildcards. (3) We propose an efficient exact algorithm, called StemFinder, for solving the MSS problem. Compared with the previous MSS algorithms, StemFinder runs much faster and reports fewer stems which represent a smaller superset of all (l, d) motifs. StemFinder is freely available at http://sites.google.com/site/feqond/stemfinder.

  2. Design of Fashion Accessories Using Akwa-Ocha Motifs and Symbols

    African Journals Online (AJOL)

    The exploration of Akwa-Ocha motifs and symbols for the design of fashion accessories for obvious reasons include creating an identity, checking the emphasis already placed on foreign fashion accessories, creating awareness and projecting one of Nigeria's rich cultural heritages. Key Words: Akwa-Ocha, motifs, symbols, ...

  3. World Color Survey color naming reveals universal motifs and their within-language diversity.

    Science.gov (United States)

    Lindsey, Delwin T; Brown, Angela M

    2009-11-24

    We analyzed the color terms in the World Color Survey (WCS) (www.icsi.berkeley.edu/wcs/), a large color-naming database obtained from informants of mostly unwritten languages spoken in preindustrialized cultures that have had limited contact with modern, industrialized society. The color naming idiolects of 2,367 WCS informants fall into three to six "motifs," where each motif is a different color-naming system based on a subset of a universal glossary of 11 color terms. These motifs are universal in that they occur worldwide, with some individual variation, in completely unrelated languages. Strikingly, these few motifs are distributed across the WCS informants in such a way that multiple motifs occur in most languages. Thus, the culture a speaker comes from does not completely determine how he or she will use color terms. An analysis of the modern patterns of motif usage in the WCS languages, based on the assumption that they reflect historical patterns of color term evolution, suggests that color lexicons have changed over time in a complex but orderly way. The worldwide distribution of the motifs and the cooccurrence of multiple motifs within languages suggest that universal processes control the naming of colors.

  4. Bayesian multiple-instance motif discovery with BAMBI: inference of recombinase and transcription factor binding sites.

    Science.gov (United States)

    Jajamovich, Guido H; Wang, Xiaodong; Arkin, Adam P; Samoilov, Michael S

    2011-11-01

    Finding conserved motifs in genomic sequences represents one of essential bioinformatic problems. However, achieving high discovery performance without imposing substantial auxiliary constraints on possible motif features remains a key algorithmic challenge. This work describes BAMBI-a sequential Monte Carlo motif-identification algorithm, which is based on a position weight matrix model that does not require additional constraints and is able to estimate such motif properties as length, logo, number of instances and their locations solely on the basis of primary nucleotide sequence data. Furthermore, should biologically meaningful information about motif attributes be available, BAMBI takes advantage of this knowledge to further refine the discovery results. In practical applications, we show that the proposed approach can be used to find sites of such diverse DNA-binding molecules as the cAMP receptor protein (CRP) and Din-family site-specific serine recombinases. Results obtained by BAMBI in these and other settings demonstrate better statistical performance than any of the four widely-used profile-based motif discovery methods: MEME, BioProspector with BioOptimizer, SeSiMCMC and Motif Sampler as measured by the nucleotide-level correlation coefficient. Additionally, in the case of Din-family recombinase target site discovery, the BAMBI-inferred motif is found to be the only one functionally accurate from the underlying biochemical mechanism standpoint. C++ and Matlab code is available at http://www.ee.columbia.edu/~guido/BAMBI or http://genomics.lbl.gov/BAMBI/.

  5. MOMFER: A Search Engine of Thompson's Motif-Index of Folk Literature

    NARCIS (Netherlands)

    Karsdorp, F.B.; van der Meulen, Marten; Meder, Theo; van den Bosch, Antal

    2015-01-01

    More than fifty years after the first edition of Thompson's seminal Motif-Indexof Folk Literature, we present an online search engine tailored to fully disclose the index digitally. This search engine, called MOMFER, greatly enhances the searchability of the Motif-Index and provides exciting new

  6. Observed and predicted hydrogen bond motifs in crystal structures of hydantoins, dihydrouracils and uracils

    NARCIS (Netherlands)

    Cruz-Cabeza, A.J.; Schwalbe, C.H.

    2012-01-01

    A survey of crystal structures containing hydantoin, dihydrouracil and uracil derivatives in the Cambridge Structural Database revealed four main types of hydrogen bond motifs when derivatives with extra substituents able to interfere with the main motif are excluded. All these molecules contain two

  7. Genome-wide conserved consensus transcription factor binding motifs are hyper-methylated

    Directory of Open Access Journals (Sweden)

    Down Thomas A

    2010-09-01

    Full Text Available Abstract Background DNA methylation can regulate gene expression by modulating the interaction between DNA and proteins or protein complexes. Conserved consensus motifs exist across the human genome ("predicted transcription factor binding sites": "predicted TFBS" but the large majority of these are proven by chromatin immunoprecipitation and high throughput sequencing (ChIP-seq not to be biological transcription factor binding sites ("empirical TFBS". We hypothesize that DNA methylation at conserved consensus motifs prevents promiscuous or disorderly transcription factor binding. Results Using genome-wide methylation maps of the human heart and sperm, we found that all conserved consensus motifs as well as the subset of those that reside outside CpG islands have an aggregate profile of hyper-methylation. In contrast, empirical TFBS with conserved consensus motifs have a profile of hypo-methylation. 40% of empirical TFBS with conserved consensus motifs resided in CpG islands whereas only 7% of all conserved consensus motifs were in CpG islands. Finally we further identified a minority subset of TF whose profiles are either hypo-methylated or neutral at their respective conserved consensus motifs implicating that these TF may be responsible for establishing or maintaining an un-methylated DNA state, or whose binding is not regulated by DNA methylation. Conclusions Our analysis supports the hypothesis that at least for a subset of TF, empirical binding to conserved consensus motifs genome-wide may be controlled by DNA methylation.

  8. Identification and characterization of subfamily-specific signatures in a large protein superfamily by a hidden Markov model approach

    Directory of Open Access Journals (Sweden)

    Ikura Mitsuhiko

    2002-01-01

    Full Text Available Abstract Background Most profile and motif databases strive to classify protein sequences into a broad spectrum of protein families. The next step of such database studies should include the development of classification systems capable of distinguishing between subfamilies within a structurally and functionally diverse superfamily. This would be helpful in elucidating sequence-structure-function relationships of proteins. Results Here, we present a method to diagnose sequences into subfamilies by employing hidden Markov models (HMMs to find windows of residues that are distinct among subfamilies (called signatures. The method starts with a multiple sequence alignment (MSA of the subfamily. Then, we build a HMM database representing all sliding windows of the MSA of a fixed size. Finally, we construct a HMM histogram of the matches of each sliding window in the entire superfamily. To illustrate the efficacy of the method, we have applied the analysis to find subfamily signatures in two well-studied superfamilies: the cadherin and the EF-hand protein superfamilies. As a corollary, the HMM histograms of the analyzed subfamilies revealed information about their Ca2+ binding sites and loops. Conclusions The method is used to create HMM databases to diagnose subfamilies of protein superfamilies that complement broad profile and motif databases such as BLOCKS, PROSITE, Pfam, SMART, PRINTS and InterPro.

  9. Does Twitter trigger bursts in signature collections?

    Science.gov (United States)

    Yamaguchi, Rui; Imoto, Seiya; Kami, Masahiro; Watanabe, Kenji; Miyano, Satoru; Yuji, Koichiro

    2013-01-01

    The quantification of social media impacts on societal and political events is a difficult undertaking. The Japanese Society of Oriental Medicine started a signature-collecting campaign to oppose a medical policy of the Government Revitalization Unit to exclude a traditional Japanese medicine, "Kampo," from the public insurance system. The signature count showed a series of aberrant bursts from November 26 to 29, 2009. In the same interval, the number of messages on Twitter including the keywords "Signature" and "Kampo," increased abruptly. Moreover, the number of messages on an Internet forum that discussed the policy and called for signatures showed a train of spikes. In order to estimate the contributions of social media, we developed a statistical model with state-space modeling framework that distinguishes the contributions of multiple social media in time-series of collected public opinions. We applied the model to the time-series of signature counts of the campaign and quantified contributions of two social media, i.e., Twitter and an Internet forum, by the estimation. We found that a considerable portion (78%) of the signatures was affected from either of the social media throughout the campaign and the Twitter effect (26%) was smaller than the Forum effect (52%) in total, although Twitter probably triggered the initial two bursts of signatures. Comparisons of the estimated profiles of the both effects suggested distinctions between the social media in terms of sustainable impact of messages or tweets. Twitter shows messages on various topics on a time-line; newer messages push out older ones. Twitter may diminish the impact of messages that are tweeted intermittently. The quantification of social media impacts is beneficial to better understand people's tendency and may promote developing strategies to engage public opinions effectively. Our proposed method is a promising tool to explore information hidden in social phenomena.

  10. Does Twitter trigger bursts in signature collections?

    Directory of Open Access Journals (Sweden)

    Rui Yamaguchi

    Full Text Available INTRODUCTION: The quantification of social media impacts on societal and political events is a difficult undertaking. The Japanese Society of Oriental Medicine started a signature-collecting campaign to oppose a medical policy of the Government Revitalization Unit to exclude a traditional Japanese medicine, "Kampo," from the public insurance system. The signature count showed a series of aberrant bursts from November 26 to 29, 2009. In the same interval, the number of messages on Twitter including the keywords "Signature" and "Kampo," increased abruptly. Moreover, the number of messages on an Internet forum that discussed the policy and called for signatures showed a train of spikes. METHODS AND FINDINGS: In order to estimate the contributions of social media, we developed a statistical model with state-space modeling framework that distinguishes the contributions of multiple social media in time-series of collected public opinions. We applied the model to the time-series of signature counts of the campaign and quantified contributions of two social media, i.e., Twitter and an Internet forum, by the estimation. We found that a considerable portion (78% of the signatures was affected from either of the social media throughout the campaign and the Twitter effect (26% was smaller than the Forum effect (52% in total, although Twitter probably triggered the initial two bursts of signatures. Comparisons of the estimated profiles of the both effects suggested distinctions between the social media in terms of sustainable impact of messages or tweets. Twitter shows messages on various topics on a time-line; newer messages push out older ones. Twitter may diminish the impact of messages that are tweeted intermittently. CONCLUSIONS: The quantification of social media impacts is beneficial to better understand people's tendency and may promote developing strategies to engage public opinions effectively. Our proposed method is a promising tool to explore

  11. Evolution, homology conservation, and identification of unique sequence signatures in GH19 family chitinases.

    Science.gov (United States)

    Udaya Prakash, N A; Jayanthi, M; Sabarinathan, R; Kangueane, P; Mathew, Lazar; Sekar, K

    2010-05-01

    The discovery of GH (Glycoside Hydrolase) 19 chitinases in Streptomyces sp. raises the possibility of the presence of these proteins in other bacterial species, since they were initially thought to be confined to higher plants. The present study mainly concentrates on the phylogenetic distribution and homology conservation in GH19 family chitinases. Extensive database searches are performed to identify the presence of GH19 family chitinases in the three major super kingdoms of life. Multiple sequence alignment of all the identified GH19 chitinase family members resulted in the identification of globally conserved residues. We further identified conserved sequence motifs across the major sub groups within the family. Estimation of evolutionary distance between the various bacterial and plant chitinases are carried out to better understand the pattern of evolution. Our study also supports the horizontal gene transfer theory, which states that GH19 chitinase genes are transferred from higher plants to bacteria. Further, the present study sheds light on the phylogenetic distribution and identifies unique sequence signatures that define GH19 chitinase family of proteins. The identified motifs could be used as markers to delineate uncharacterized GH19 family chitinases. The estimation of evolutionary distance between chitinase identified in plants and bacteria shows that the flowering plants are more related to chitinase in actinobacteria than that of identified in purple bacteria. We propose a model to elucidate the natural history of GH19 family chitinases.

  12. Seed storage protein gene promoters contain conserved DNA motifs in Brassicaceae, Fabaceae and Poaceae

    Science.gov (United States)

    Fauteux, François; Strömvik, Martina V

    2009-01-01

    Background Accurate computational identification of cis-regulatory motifs is difficult, particularly in eukaryotic promoters, which typically contain multiple short and degenerate DNA sequences bound by several interacting factors. Enrichment in combinations of rare motifs in the promoter sequence of functionally or evolutionarily related genes among several species is an indicator of conserved transcriptional regulatory mechanisms. This provides a basis for the computational identification of cis-regulatory motifs. Results We have used a discriminative seeding DNA motif discovery algorithm for an in-depth analysis of 54 seed storage protein (SSP) gene promoters from three plant families, namely Brassicaceae (mustards), Fabaceae (legumes) and Poaceae (grasses) using backgrounds based on complete sets of promoters from a representative species in each family, namely Arabidopsis (Arabidopsis thaliana (L.) Heynh.), soybean (Glycine max (L.) Merr.) and rice (Oryza sativa L.) respectively. We have identified three conserved motifs (two RY-like and one ACGT-like) in Brassicaceae and Fabaceae SSP gene promoters that are similar to experimentally characterized seed-specific cis-regulatory elements. Fabaceae SSP gene promoter sequences are also enriched in a novel, seed-specific E2Fb-like motif. Conserved motifs identified in Poaceae SSP gene promoters include a GCN4-like motif, two prolamin-box-like motifs and an Skn-1-like motif. Evidence of the presence of a variant of the TATA-box is found in the SSP gene promoters from the three plant families. Motifs discovered in SSP gene promoters were used to score whole-genome sets of promoters from Arabidopsis, soybean and rice. The highest-scoring promoters are associated with genes coding for different subunits or precursors of seed storage proteins. Conclusion Seed storage protein gene promoter motifs are conserved in diverse species, and different plant families are characterized by a distinct combination of conserved motifs

  13. Seed storage protein gene promoters contain conserved DNA motifs in Brassicaceae, Fabaceae and Poaceae

    Directory of Open Access Journals (Sweden)

    Fauteux François

    2009-10-01

    Full Text Available Abstract Background Accurate computational identification of cis-regulatory motifs is difficult, particularly in eukaryotic promoters, which typically contain multiple short and degenerate DNA sequences bound by several interacting factors. Enrichment in combinations of rare motifs in the promoter sequence of functionally or evolutionarily related genes among several species is an indicator of conserved transcriptional regulatory mechanisms. This provides a basis for the computational identification of cis-regulatory motifs. Results We have used a discriminative seeding DNA motif discovery algorithm for an in-depth analysis of 54 seed storage protein (SSP gene promoters from three plant families, namely Brassicaceae (mustards, Fabaceae (legumes and Poaceae (grasses using backgrounds based on complete sets of promoters from a representative species in each family, namely Arabidopsis (Arabidopsis thaliana (L. Heynh., soybean (Glycine max (L. Merr. and rice (Oryza sativa L. respectively. We have identified three conserved motifs (two RY-like and one ACGT-like in Brassicaceae and Fabaceae SSP gene promoters that are similar to experimentally characterized seed-specific cis-regulatory elements. Fabaceae SSP gene promoter sequences are also enriched in a novel, seed-specific E2Fb-like motif. Conserved motifs identified in Poaceae SSP gene promoters include a GCN4-like motif, two prolamin-box-like motifs and an Skn-1-like motif. Evidence of the presence of a variant of the TATA-box is found in the SSP gene promoters from the three plant families. Motifs discovered in SSP gene promoters were used to score whole-genome sets of promoters from Arabidopsis, soybean and rice. The highest-scoring promoters are associated with genes coding for different subunits or precursors of seed storage proteins. Conclusion Seed storage protein gene promoter motifs are conserved in diverse species, and different plant families are characterized by a distinct combination

  14. Methods for Identifying Ligands that Target Nucleic Acid Molecules and Nucleic Acid Structural Motifs

    Science.gov (United States)

    Disney, Matthew D. (Inventor); Childs-Disney, Jessica L. (Inventor)

    2017-01-01

    Disclosed are methods for identifying a nucleic acid (e.g., RNA, DNA, etc.) motif which interacts with a ligand. The method includes providing a plurality of ligands immobilized on a support, wherein each particular ligand is immobilized at a discrete location on the support; contacting the plurality of immobilized ligands with a nucleic acid motif library under conditions effective for one or more members of the nucleic acid motif library to bind with the immobilized ligands; and identifying members of the nucleic acid motif library that are bound to a particular immobilized ligand. Also disclosed are methods for selecting, from a plurality of candidate ligands, one or more ligands that have increased likelihood of binding to a nucleic acid molecule comprising a particular nucleic acid motif, as well as methods for identifying a nucleic acid which interacts with a ligand.

  15. Use of BONSAI decision trees for the identification of potential MHC class I peptide epitope motifs.

    Science.gov (United States)

    Savoie, C J; Kamikawaji, N; Sasazuki, T; Kuhara, S

    1999-01-01

    Recognition of short peptides of 8 to 10 mer bound to MHC class I molecules by cytotoxic T lymphocytes forms the basis of cellular immunity. While the sequence motifs necessary for binding of intracellular peptides to MHC have been well studied, little is known about sequence motifs that may cause preferential affinity to the T cell receptor and/or preferential recognition and response by T cells. Here we demonstrate that computational learning systems can be useful to elucidate sequence motifs that affect T cell activation. Knowledge of T cell activation motifs could be useful for targeted vaccine design or immunotherapy. With the BONSAI computational learning algorithm, using a database of previously reported MHC bound peptides that had positive or negative T cell responses, we were able to identify sequence motif rules that explain 70% of positive T cell responses and 84% of negative T cell responses.

  16. A Conserved Motif Provides Binding Specificity to the PP2A-B56 Phosphatase

    DEFF Research Database (Denmark)

    Hertz, Emil Peter Thrane; Kruse, Thomas; Davey, Norman E

    2016-01-01

    -exposed pocket on PP2A regulatory B56 subunits binds to a consensus sequence on interacting proteins, which we term the LxxIxE motif. The composition of the motif modulates the affinity for B56, which in turn determines the phosphorylation status of associated substrates. Phosphorylation of amino acid residues......Dynamic protein phosphorylation is a fundamental mechanism regulating biological processes in all organisms. Protein phosphatase 2A (PP2A) is the main source of phosphatase activity in the cell, but the molecular details of substrate recognition are unknown. Here, we report that a conserved surface...... within the motif increases B56 binding, allowing integration of kinase and phosphatase activity. We identify conserved LxxIxE motifs in essential proteins throughout the eukaryotic domain of life and in human viruses, suggesting that the motifs are required for basic cellular function. Our study provides...

  17. Stochastic and coherence resonance in feed-forward-loop neuronal network motifs

    Science.gov (United States)

    Guo, Daqing; Li, Chunguang

    2009-05-01

    The relationships between noise and complex dynamic behaviors of neuronal ensembles are key questions in computational neuroscience, particularly in understanding some basic signal transmission mechanisms of the brain. Here we systemically investigate both the stochastic resonance (SR) and coherence resonance (CR) in the triple-neuron feed-forward-loop (FFL) network motifs by computational modeling. We use the Izhikevich neuron model as well as the chemical coupling to build the FFL motifs, and consider all possible motif types. The simulation results demonstrate that these motifs can exploit noise to enrich its dynamic performance. With a proper choice of noise intensities, both the SR and CR can be exhibited in many types of the FFLs. On the other hand, our results also indicate that the coupling strength serves as a control parameter, which has great impacts on the stochastic dynamics of the FFL motifs. Additionally, biological implications of presented results in the field of neuroscience are outlined.

  18. MotifMap-RNA: a genome-wide map of RBP binding sites.

    Science.gov (United States)

    Liu, Yu; Sun, Sha; Bredy, Timothy; Wood, Marcelo; Spitale, Robert C; Baldi, Pierre

    2017-07-01

    RNA plays a critical role in gene expression and its regulation. RNA binding proteins (RBPs), in turn, are important regulators of RNA. Thanks to the availability of large scale data for RBP binding motifs and in vivo binding sites results in the form of eCLIP experiments, it is now possible to computationally predict RBP binding sites across the whole genome. We describe MotifMap-RNA, an extension of MotifMap which predicts binding sites for RBP motifs across human and mouse genomes and allows large scale querying of predicted binding sites. The data and corresponding web server are available from: http://motifmap-rna.ics.uci.edu/ as part of the MotifMap web portal. rspitale@uci.edu or pfbaldi@uci.edu. Supplementary data are available at Bioinformatics online.

  19. RSAT::Plants: Motif Discovery Within Clusters of Upstream Sequences in Plant Genomes.

    Science.gov (United States)

    Contreras-Moreira, Bruno; Castro-Mondragon, Jaime A; Rioualen, Claire; Cantalapiedra, Carlos P; van Helden, Jacques

    2016-01-01

    The plant-dedicated mirror of the Regulatory Sequence Analysis Tools (RSAT, http://plants.rsat.eu ) offers specialized options for researchers dealing with plant transcriptional regulation. The website contains whole-sequenced genomes from species regularly updated from Ensembl Plants and other sources (currently 40), and supports an array of tasks frequently required for the analysis of regulatory sequences, such as retrieving upstream sequences, motif discovery, motif comparison, and pattern matching. RSAT::Plants also integrates the footprintDB collection of DNA motifs. This protocol explains step-by-step how to discover DNA motifs in regulatory regions of clusters of co-expressed genes in plants. It also explains how to empirically control the significance of the result, and how to associate the discovered motifs with putative binding factors.

  20. Research on a New Signature Scheme on Blockchain

    Directory of Open Access Journals (Sweden)

    Chao Yuan

    2017-01-01

    Full Text Available With the rise of Bitcoin, blockchain which is the core technology of Bitcoin has received increasing attention. Privacy preserving and performance on blockchain are two research points in academia and business, but there are still some unresolved issues in both respects. An aggregate signature scheme is a digital signature that supports making signatures on many different messages generated by many different users. Using aggregate signature, the size of the signature could be shortened by compressing multiple signatures into a single signature. In this paper, a new signature scheme for transactions on blockchain based on the aggregate signature was proposed. It was worth noting that elliptic curve discrete logarithm problem and bilinear maps played major roles in our signature scheme. And the security properties of our signature scheme were proved. In our signature scheme, the amount will be hidden especially in the transactions which contain multiple inputs and outputs. Additionally, the size of the signature on transaction is constant regardless of the number of inputs and outputs that the transaction contains, which can improve the performance of signature. Finally, we gave an application scenario for our signature scheme which aims to achieve the transactions of big data on blockchain.

  1. Cellular automata simulation of topological effects on the dynamics of feed-forward motifs

    Science.gov (United States)

    Apte, Advait A; Cain, John W; Bonchev, Danail G; Fong, Stephen S

    2008-01-01

    Background Feed-forward motifs are important functional modules in biological and other complex networks. The functionality of feed-forward motifs and other network motifs is largely dictated by the connectivity of the individual network components. While studies on the dynamics of motifs and networks are usually devoted to the temporal or spatial description of processes, this study focuses on the relationship between the specific architecture and the overall rate of the processes of the feed-forward family of motifs, including double and triple feed-forward loops. The search for the most efficient network architecture could be of particular interest for regulatory or signaling pathways in biology, as well as in computational and communication systems. Results Feed-forward motif dynamics were studied using cellular automata and compared with differential equation modeling. The number of cellular automata iterations needed for a 100% conversion of a substrate into a target product was used as an inverse measure of the transformation rate. Several basic topological patterns were identified that order the specific feed-forward constructions according to the rate of dynamics they enable. At the same number of network nodes and constant other parameters, the bi-parallel and tri-parallel motifs provide higher network efficacy than single feed-forward motifs. Additionally, a topological property of isodynamicity was identified for feed-forward motifs where different network architectures resulted in the same overall rate of the target production. Conclusion It was shown for classes of structural motifs with feed-forward architecture that network topology affects the overall rate of a process in a quantitatively predictable manner. These fundamental results can be used as a basis for simulating larger networks as combinations of smaller network modules with implications on studying synthetic gene circuits, small regulatory systems, and eventually dynamic whole-cell models

  2. Integrating Temporal and Spatial Scales: Human Structural Network Motifs Across Age and Region of Interest Size

    Science.gov (United States)

    Echtermeyer, Christoph; Han, Cheol E.; Rotarska-Jagiela, Anna; Mohr, Harald; Uhlhaas, Peter J.; Kaiser, Marcus

    2011-01-01

    Human brain networks can be characterized at different temporal or spatial scales given by the age of the subject or the spatial resolution of the neuroimaging method. Integration of data across scales can only be successful if the combined networks show a similar architecture. One way to compare networks is to look at spatial features, based on fiber length, and topological features of individual nodes where outlier nodes form single node motifs whose frequency yields a fingerprint of the network. Here, we observe how characteristic single node motifs change over age (12–23 years) and network size (414, 813, and 1615 nodes) for diffusion tensor imaging structural connectivity in healthy human subjects. First, we find the number and diversity of motifs in a network to be strongly correlated. Second, comparing different scales, the number and diversity of motifs varied across the temporal (subject age) and spatial (network resolution) scale: certain motifs might only occur at one spatial scale or for a certain age range. Third, regions of interest which show one motif at a lower resolution may show a range of motifs at a higher resolution which may or may not include the original motif at the lower resolution. Therefore, both the type and localization of motifs differ for different spatial resolutions. Our results also indicate that spatial resolution has a higher effect on topological measures whereas spatial measures, based on fiber lengths, remain more comparable between resolutions. Therefore, spatial resolution is crucial when comparing characteristic node fingerprints given by topological and spatial network features. As node motifs are based on topological and spatial properties of brain connectivity networks, these conclusions are also relevant to other studies using connectome analysis. PMID:21811454

  3. MOCCS: Clarifying DNA-binding motif ambiguity using ChIP-Seq data.

    Science.gov (United States)

    Ozaki, Haruka; Iwasaki, Wataru

    2016-08-01

    As a key mechanism of gene regulation, transcription factors (TFs) bind to DNA by recognizing specific short sequence patterns that are called DNA-binding motifs. A single TF can accept ambiguity within its DNA-binding motifs, which comprise both canonical (typical) and non-canonical motifs. Clarification of such DNA-binding motif ambiguity is crucial for revealing gene regulatory networks and evaluating mutations in cis-regulatory elements. Although chromatin immunoprecipitation sequencing (ChIP-seq) now provides abundant data on the genomic sequences to which a given TF binds, existing motif discovery methods are unable to directly answer whether a given TF can bind to a specific DNA-binding motif. Here, we report a method for clarifying the DNA-binding motif ambiguity, MOCCS. Given ChIP-Seq data of any TF, MOCCS comprehensively analyzes and describes every k-mer to which that TF binds. Analysis of simulated datasets revealed that MOCCS is applicable to various ChIP-Seq datasets, requiring only a few minutes per dataset. Application to the ENCODE ChIP-Seq datasets proved that MOCCS directly evaluates whether a given TF binds to each DNA-binding motif, even if known position weight matrix models do not provide sufficient information on DNA-binding motif ambiguity. Furthermore, users are not required to provide numerous parameters or background genomic sequence models that are typically unavailable. MOCCS is implemented in Perl and R and is freely available via https://github.com/yuifu/moccs. By complementing existing motif-discovery software, MOCCS will contribute to the basic understanding of how the genome controls diverse cellular processes via DNA-protein interactions. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Lattice-Based Revocable Certificateless Signature

    Directory of Open Access Journals (Sweden)

    Ying-Hao Hung

    2017-10-01

    Full Text Available Certificateless signatures (CLS are noticeable because they may resolve the key escrow problem in ID-based signatures and break away the management problem regarding certificate in conventional signatures. However, the security of the mostly previous CLS schemes relies on the difficulty of solving discrete logarithm or large integer factorization problems. These two problems would be solved by quantum computers in the future so that the signature schemes based on them will also become insecure. For post-quantum cryptography, lattice-based cryptography is significant due to its efficiency and security. However, no study on addressing the revocation problem in the existing lattice-based CLS schemes is presented. In this paper, we focus on the revocation issue and present the first revocable CLS (RCLS scheme over lattices. Based on the short integer solution (SIS assumption over lattices, the proposed lattice-based RCLS scheme is shown to be existential unforgeability against adaptive chosen message attacks. By performance analysis and comparisons, the proposed lattice-based RCLS scheme is better than the previously proposed lattice-based CLS scheme, in terms of private key size, signature length and the revocation mechanism.

  5. Univalent binding of the Cry1Ab toxin of Bacillus thuringiensis to a conserved structural motif in the cadherin receptor BT-R1.

    Science.gov (United States)

    Griko, Natalya B; Rose-Young, Laura; Zhang, Xuebin; Carpenter, Lindy; Candas, Mehmet; Ibrahim, Mohamed A; Junker, Matthew; Bulla, Lee A

    2007-09-04

    The Cry1Ab toxin produced by Bacillus thuringiensis (Bt) exerts insecticidal action upon binding to BT-R1, a cadherin receptor localized in the midgut epithelium of the tobacco hornworm Manduca sexta [Dorsch, J. A., Candas, M., Griko, N. B., Maaty, W. S., Midboe, E. G., Vadlamudi, R. K., and Bulla, L. A., Jr. (2002) Cry1A toxins of Bacillus thuringiensis bind specifically to a region adjacent to the membrane-proximal extracellular domain of BT-R1 in Manduca sexta: involvement of a cadherin in the entomopathogenicity of Bacillus thuringiensis, Insect Biochem. Mol. Biol. 32, 1025-1036]. BT-R1 represents a family of invertebrate cadherins whose ectodomains (ECs) are composed of multiple cadherin repeats (EC1 through EC12). In the present work, we determined the Cry1Ab toxin binding site in BT-R1 in the context of cadherin structural determinants. Our studies revealed a conserved structural motif for toxin binding that includes two distinct regions within the N- and C-termini of EC12. These regions are characterized by unique sequence signatures that mark the toxin-binding function in BT-R1 as well as in homologous lepidopteran cadherins. Structure modeling of EC12 discloses the conserved motif as a single broad interface that holds the N- and C-termini in close proximity. Binding of toxin to BT-R1, which is univalent, and the subsequent downstream molecular events responsible for cell death depend on the conserved motif in EC12.

  6. One motif to bind them: A small-XXX-small motif affects transmembrane domain 1 oligomerization, function, localization, and cross-talk between two yeast GPCRs.

    Science.gov (United States)

    Lock, Antonia; Forfar, Rachel; Weston, Cathryn; Bowsher, Leo; Upton, Graham J G; Reynolds, Christopher A; Ladds, Graham; Dixon, Ann M

    2014-12-01

    G protein-coupled receptors (GPCRs) are the largest family of cell-surface receptors in mammals and facilitate a range of physiological responses triggered by a variety of ligands. GPCRs were thought to function as monomers, however it is now accepted that GPCR homo- and hetero-oligomers also exist and influence receptor properties. The Schizosaccharomyces pombe GPCR Mam2 is a pheromone-sensing receptor involved in mating and has previously been shown to form oligomers in vivo. The first transmembrane domain (TMD) of Mam2 contains a small-XXX-small motif, overrepresented in membrane proteins and well-known for promoting helix-helix interactions. An ortholog of Mam2 in Saccharomyces cerevisiae, Ste2, contains an analogous small-XXX-small motif which has been shown to contribute to receptor homo-oligomerization, localization and function. Here we have used experimental and computational techniques to characterize the role of the small-XXX-small motif in function and assembly of Mam2 for the first time. We find that disruption of the motif via mutagenesis leads to reduction of Mam2 TMD1 homo-oligomerization and pheromone-responsive cellular signaling of the full-length protein. It also impairs correct targeting to the plasma membrane. Mutation of the analogous motif in Ste2 yielded similar results, suggesting a conserved mechanism for assembly. Using co-expression of the two fungal receptors in conjunction with computational models, we demonstrate a functional change in G protein specificity and propose that this is brought about through hetero-dimeric interactions of Mam2 with Ste2 via the complementary small-XXX-small motifs. This highlights the potential of these motifs to affect a range of properties that can be investigated in other GPCRs. Copyright © 2014. Published by Elsevier B.V.

  7. Quantum mechanical stabilization of Minkowski signature wormholes

    Energy Technology Data Exchange (ETDEWEB)

    Visser, M.

    1989-05-19

    When one attempts to construct classical wormholes in Minkowski signature Lorentzian spacetimes violations of both the weak energy hypothesis and averaged weak energy hypothesis are encountered. Since the weak energy hypothesis is experimentally known to be violated quantum mechanically, this suggests that a quantum mechanical analysis of Minkowski signature wormholes is in order. In this note I perform a minisuperspace analysis of a simple class of Minkowski signature wormholes. By solving the Wheeler-de Witt equation for pure Einstein gravity on this minisuperspace the quantum mechanical wave function of the wormhole is obtained in closed form. The wormhole is shown to be quantum mechanically stabilized with an average radius of order the Planck length. 8 refs.

  8. Digital signature of electronic dental records.

    Science.gov (United States)

    Maruo, Ivan Toshio; Maruo, Hiroshi

    2012-05-01

    The purpose of this article is to examine the feasibility of digital signature technology to guarantee the legal validation of electronic dental records. The possible uses of digital signature technology, the actual use of digital signature technology to authenticate electronic dental records, the authentication of each part of the electronic dental record, the general legal principles involved, how to digitally sign electronic dental record files, and the limitations of this method are discussed. It is possible to obtain electronic dental records that carry the same legal certainty as conventional, nonelectronic records. For this purpose, each part of the electronic dental records should be digitally signed by the author of the document. Copyright © 2012 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

  9. A Methodology for Calculating Radiation Signatures

    Energy Technology Data Exchange (ETDEWEB)

    Klasky, Marc Louis [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Wilcox, Trevor [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Bathke, Charles G. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); James, Michael R. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-05-01

    A rigorous formalism is presented for calculating radiation signatures from both Special Nuclear Material (SNM) as well as radiological sources. The use of MCNP6 in conjunction with CINDER/ORIGEN is described to allow for the determination of both neutron and photon leakages from objects of interest. In addition, a description of the use of MCNP6 to properly model the background neutron and photon sources is also presented. Examinations of the physics issues encountered in the modeling are investigated so as to allow for guidance in the user discerning the relevant physics to incorporate into general radiation signature calculations. Furthermore, examples are provided to assist in delineating the pertinent physics that must be accounted for. Finally, examples of detector modeling utilizing MCNP are provided along with a discussion on the generation of Receiver Operating Curves, which are the suggested means by which to determine detectability radiation signatures emanating from objects.

  10. Cryptanalysis of the arbitrated quantum signature protocols

    Energy Technology Data Exchange (ETDEWEB)

    Gao Fei; Qin Sujuan; Guo Fenzhuo; Wen Qiaoyan [State Key Laboratory of Networking and Switching Technology, Beijing University of Posts and Telecommunications, Beijing 100876 (China)

    2011-08-15

    As a new model for signing quantum messages, arbitrated quantum signature (AQS) has recently received a lot of attention. In this paper we study the cryptanalysis of previous AQS protocols from the aspects of forgery and disavowal. We show that in these protocols the receiver, Bob, can realize existential forgery of the sender's signature under known message attack. Bob can even achieve universal forgery when the protocols are used to sign a classical message. Furthermore, the sender, Alice, can successfully disavow any of her signatures by simple attack. The attack strategies are described in detail and some discussions about the potential improvements of the protocols are given. Finally we also present several interesting topics on AQS protocols that can be studied in future.

  11. Low Scale Gravity Signatures in ATLAS

    CERN Document Server

    Karagoz-Unel, M

    2008-01-01

    The ATLAS detector may reveal in the LHC collisions signatures of extra dimensional models which predict quantum gravity at the TeV scale. One of the most dramatic consequences of such models is the copious production of micro blackholes. Micro blackholes can yield distinct signatures with large multiplicity and large energy release in the ATLAS detector. Extra dimensional models also predict the existence of Kaluza-Klein partners of SM gauge bosons, such as the excited graviton and gluon. These particles can be searched for in their two-body decays. The emerging final state particles are highly energetic, thus requiring novel reconstruction techniques, in particular in the heavy quark (t, b) channels. I will summarize the current status of the low scale gravity studies in ATLAS with example signatures.

  12. A possible signature of annihilating dark matter

    Science.gov (United States)

    Chan, Man Ho

    2018-02-01

    In this article, we report a new signature of dark matter annihilation based on the radio continuum data of NGC 1569 galaxy detected in the past few decades. After eliminating the thermal contribution of the radio signal, an abrupt change in the spectral index is shown in the radio spectrum. Previously, this signature was interpreted as an evidence of convective outflow of cosmic ray. However, we show that the cosmic ray contribution is not enough to account for the observed radio flux. We then discover that if dark matter annihilates via the 4-e channel with the thermal relic cross-section, the electrons and positrons produced would emit a strong radio flux which can provide an excellent agreement with the observed signature. The best-fitting dark matter mass is 25 GeV.

  13. Regulation of GPCR Anterograde Trafficking by Molecular Chaperones and Motifs.

    Science.gov (United States)

    Young, Brent; Wertman, Jaime; Dupré, Denis J

    2015-01-01

    G protein-coupled receptors (GPCRs) make up a superfamily of integral membrane proteins that respond to a wide variety of extracellular stimuli, giving them an important role in cell function and survival. They have also proven to be valuable targets in the fight against various diseases. As such, GPCR signal regulation has received considerable attention over the last few decades. With the amplitude of signaling being determined in large part by receptor density at the plasma membrane, several endogenous mechanisms for modulating GPCR expression at the cell surface have come to light. It has been shown that cell surface expression is determined by both exocytic and endocytic processes. However, the body of knowledge surrounding GPCR trafficking from the endoplasmic reticulum to the plasma membrane, commonly known as anterograde trafficking, has considerable room for growth. We focus here on the current paradigms of anterograde GPCR trafficking. We will discuss the regulatory role of both the general and "nonclassical private" chaperone systems in GPCR trafficking as well as conserved motifs that serve as modulators of GPCR export from the endoplasmic reticulum and Golgi apparatus. Together, these topics summarize some of the known mechanisms by which the cell regulates anterograde GPCR trafficking. © 2015 Elsevier Inc. All rights reserved.

  14. Peptide motif analysis predicts alphaviruses as triggers for rheumatoid arthritis.

    Science.gov (United States)

    Hogeboom, Charissa

    2015-12-01

    Rheumatoid arthritis (RA) develops in response to both genetic and environmental factors. The strongest genetic determinant is HLA-DR, where polymorphisms within the P4 and P6 binding pockets confer elevated risk. However, low disease concordance across monozygotic twin pairs underscores the importance of an environmental factor, probably infectious. The goal of this investigation was to predict the microorganism most likely to interact with HLA-DR to trigger RA under the molecular mimicry hypothesis. A set of 185 structural proteins from viruses or intracellular bacteria was scanned for regions of sequence homology with a collagen peptide that binds preferentially to DR4; candidates were then evaluated against a motif required for T cell cross-reactivity. The plausibility of the predicted agent was evaluated by comparison of microbial prevalence patterns to epidemiological characteristics of RA. Peptides from alphavirus capsid proteins provided the closest fit. Variations in the P6 position suggest that the HLA binding preference may vary by species, with Ross River virus, Chikungunya virus, and Mayaro virus peptides binding preferentially to DR4, and peptides from Sindbis/Ockelbo virus showing stronger affinity to DR1. The predicted HLA preference is supported by epidemiological studies of post-infection chronic arthralgia. Parallels between the cytokine profiles of RA and chronic alphavirus infection are discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Eukaryotic Penelope-Like Retroelements Encode Hammerhead Ribozyme Motifs

    Science.gov (United States)

    Cervera, Amelia; De la Peña, Marcos

    2014-01-01

    Small self-cleaving RNAs, such as the paradigmatic Hammerhead ribozyme (HHR), have been recently found widespread in DNA genomes across all kingdoms of life. In this work, we found that new HHR variants are preserved in the ancient family of Penelope-like elements (PLEs), a group of eukaryotic retrotransposons regarded as exceptional for encoding telomerase-like retrotranscriptases and spliceosomal introns. Our bioinformatic analysis revealed not only the presence of minimalist HHRs in the two flanking repeats of PLEs but also their massive and widespread occurrence in metazoan genomes. The architecture of these ribozymes indicates that they may work as dimers, although their low self-cleavage activity in vitro suggests the requirement of other factors in vivo. In plants, however, PLEs show canonical HHRs, whereas fungi and protist PLEs encode ribozyme variants with a stable active conformation as monomers. Overall, our data confirm the connection of self-cleaving RNAs with eukaryotic retroelements and unveil these motifs as a significant fraction of the encoded information in eukaryotic genomes. PMID:25135949

  16. DNA mutation motifs in the genes associated with inherited diseases.

    Science.gov (United States)

    Růžička, Michal; Kulhánek, Petr; Radová, Lenka; Čechová, Andrea; Špačková, Naďa; Fajkusová, Lenka; Réblová, Kamila

    2017-01-01

    Mutations in human genes can be responsible for inherited genetic disorders and cancer. Mutations can arise due to environmental factors or spontaneously. It has been shown that certain DNA sequences are more prone to mutate. These sites are termed hotspots and exhibit a higher mutation frequency than expected by chance. In contrast, DNA sequences with lower mutation frequencies than expected by chance are termed coldspots. Mutation hotspots are usually derived from a mutation spectrum, which reflects particular population where an effect of a common ancestor plays a role. To detect coldspots/hotspots unaffected by population bias, we analysed the presence of germline mutations obtained from HGMD database in the 5-nucleotide segments repeatedly occurring in genes associated with common inherited disorders, in particular, the PAH, LDLR, CFTR, F8, and F9 genes. Statistically significant sequences (mutational motifs) rarely associated with mutations (coldspots) and frequently associated with mutations (hotspots) exhibited characteristic sequence patterns, e.g. coldspots contained purine tract while hotspots showed alternating purine-pyrimidine bases, often with the presence of CpG dinucleotide. Using molecular dynamics simulations and free energy calculations, we analysed the global bending properties of two selected coldspots and two hotspots with a G/T mismatch. We observed that the coldspots were inherently more flexible than the hotspots. We assume that this property might be critical for effective mismatch repair as DNA with a mutation recognized by MutSα protein is noticeably bent.

  17. Perkembangan Motif Sineas Film Indie dalam Menghadapi Industri Film Mainstream

    Directory of Open Access Journals (Sweden)

    Yoppy Ardiyono

    2016-03-01

    Full Text Available The research aims to review to review determine the effect and its impact raised by motive - a motive the ada in the hearts period travel time history of film short against cinematographer-filmmaker as principal especially filmmakers left path (indie. The used platform theory research hearts singer adopts from theory commodification media vincent mosco. Singer helped shift theory understanding the motive filmmakers working hearts differences fundamental basis of political pressure economic happens under with demands regime. The method used is descriptive qualitative research methods. Data collection techniques through observation of the environment of an independent film live and in-depth interviews with speakers including mr. Yang prayer orangutan direct contact 'with realm of research. Coupled with study to review the literature references adding insight research. And that was concluded change appears motif among indie film cinematographer it is true the situation is closely linked to the mainstream industry, konstilasi politics, and the orientation of capitalism. Necessary their one thing is clear and systematic regulation from the government to the future movement of currents sidestream (indie more with good operates professionally arranged, the air so that the contribution of indie cinema film land for progress can feels good to yourself indie filmmakers as well as those of its main industries.

  18. Motif mediated protein-protein interactions as drug targets.

    Science.gov (United States)

    Corbi-Verge, Carles; Kim, Philip M

    2016-03-02

    Protein-protein interactions (PPI) are involved in virtually every cellular process and thus represent an attractive target for therapeutic interventions. A significant number of protein interactions are frequently formed between globular domains and short linear peptide motifs (DMI). Targeting these DMIs has proven challenging and classical approaches to inhibiting such interactions with small molecules have had limited success. However, recent new approaches have led to the discovery of potent inhibitors, some of them, such as Obatoclax, ABT-199, AEG-40826 and SAH-p53-8 are likely to become approved drugs. These novel inhibitors belong to a wide range of different molecule classes, ranging from small molecules to peptidomimetics and biologicals. This article reviews the main reasons for limited success in targeting PPIs, discusses how successful approaches overcome these obstacles to discovery promising inhibitors for human protein double minute 2 (HDM2), B-cell lymphoma 2 (Bcl-2), X-linked inhibitor of apoptosis protein (XIAP), and provides a summary of the promising approaches currently in development that indicate the future potential of PPI inhibitors in drug discovery.

  19. DNA Methylation Signatures of the Plant Chromomethyltransferases.

    Directory of Open Access Journals (Sweden)

    Quentin Gouil

    2016-12-01

    Full Text Available DNA methylation in plants is traditionally partitioned into CG, CHG and CHH contexts (with H any nucleotide but G. By investigating DNA methylation patterns in trinucleotide contexts in four angiosperm species, we show that such a representation hides spatial and functional partitioning of different methylation pathways and is incomplete. CG methylation (mCG is largely context-independent whereas, at CHG motifs, there is under-representation of mCCG in pericentric regions of A. thaliana and tomato and throughout the chromosomes of maize and rice. In A. thaliana the biased representation of mCCG in heterochromatin is related to specificities of H3K9 methyltransferase SUVH family members. At CHH motifs there is an over-representation of different variant forms of mCHH that, similarly to mCCG hypomethylation, is partitioned into the pericentric regions of the two dicots but dispersed in the monocot chromosomes. The over-represented mCHH motifs in A. thaliana associate with specific types of transposon including both class I and II elements. At mCHH the contextual bias is due to the involvement of various chromomethyltransferases whereas the context-independent CHH methylation in A. thaliana and tomato is mediated by the RNA-directed DNA methylation process that is most active in the gene-rich euchromatin. This analysis therefore reveals that the sequence context of the methylome of plant genomes is informative about the mechanisms associated with maintenance of methylation and the overlying chromatin structure.

  20. Peripheral blood signatures of lead exposure.

    Directory of Open Access Journals (Sweden)

    Heather G LaBreche

    Full Text Available BACKGROUND: Current evidence indicates that even low-level lead (Pb exposure can have detrimental effects, especially in children. We tested the hypothesis that Pb exposure alters gene expression patterns in peripheral blood cells and that these changes reflect dose-specific alterations in the activity of particular pathways. METHODOLOGY/PRINCIPAL FINDING: Using Affymetrix Mouse Genome 430 2.0 arrays, we examined gene expression changes in the peripheral blood of female Balb/c mice following exposure to per os lead acetate trihydrate or plain drinking water for two weeks and after a two-week recovery period. Data sets were RMA-normalized and dose-specific signatures were generated using established methods of supervised classification and binary regression. Pathway activity was analyzed using the ScoreSignatures module from GenePattern. CONCLUSIONS/SIGNIFICANCE: The low-level Pb signature was 93% sensitive and 100% specific in classifying samples a leave-one-out crossvalidation. The high-level Pb signature demonstrated 100% sensitivity and specificity in the leave-one-out crossvalidation. These two signatures exhibited dose-specificity in their ability to predict Pb exposure and had little overlap in terms of constituent genes. The signatures also seemed to reflect current levels of Pb exposure rather than past exposure. Finally, the two doses showed differential activation of cellular pathways. Low-level Pb exposure increased activity of the interferon-gamma pathway, whereas high-level Pb exposure increased activity of the E2F1 pathway.

  1. Transient thermal camouflage and heat signature control

    Science.gov (United States)

    Yang, Tian-Zhi; Su, Yishu; Xu, Weikai; Yang, Xiao-Dong

    2016-09-01

    Thermal metamaterials have been proposed to manipulate heat flux as a new way to cloak or camouflage objects in the infrared world. To date, however, thermal metamaterials only operate in the steady-state and exhibit detectable, transient heat signatures. In this letter, the theoretical basis for a thermal camouflaging technique with controlled transient diffusion is presented. This technique renders an object invisible in real time. More importantly, the thermal camouflaging device instantaneously generates a pre-designed heat signature and behaves as a perfect thermal illusion device. A metamaterial coating with homogeneous and isotropic thermal conductivity, density, and volumetric heat capacity was fabricated and very good camouflaging performance was achieved.

  2. Experimental quantum digital signature over 102 km

    Science.gov (United States)

    Yin, Hua-Lei; Fu, Yao; Liu, Hui; Tang, Qi-Jie; Wang, Jian; You, Li-Xing; Zhang, Wei-Jun; Chen, Si-Jing; Wang, Zhen; Zhang, Qiang; Chen, Teng-Yun; Chen, Zeng-Bing; Pan, Jian-Wei

    2017-03-01

    Quantum digital signature (QDS) is an approach to guarantee the nonrepudiation, unforgeability, and transferability of a signature with information-theoretical security. Previous experimental realizations of QDS relied on an unrealistic assumption of secure channels and the longest distance is several kilometers. Here, we have experimentally demonstrated a recently proposed QDS protocol without assuming any secure channel. Exploiting the decoy state modulation, we have successfully signed a one-bit message through an up to 102-km optical fiber. Furthermore, we continuously run the system to sign the longer message "USTC" with 32 bits at the distance of 51 km. Our results pave the way towards the practical application of QDS.

  3. State of the Art: Signature Biometrics Verification

    Directory of Open Access Journals (Sweden)

    Nourddine Guersi

    2010-04-01

    Full Text Available This paper presents a comparative analysis of the performance of three estimation algorithms: Expectation Maximization (EM, Greedy EM Algorithm (GEM and Figueiredo-Jain Algorithm (FJ - based on the Gaussian mixture models (GMMs for signature biometrics verification. The simulation results have shown significant performance achievements. The test performance of EER=5.49 % for "EM", EER=5.04 % for "GEM" and EER=5.00 % for "FJ", shows that the behavioral information scheme of signature biometrics is robust and has a discriminating power, which can be explored for identity authentication.

  4. Security problem on arbitrated quantum signature schemes

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Jeong Woon [Emerging Technology R and D Center, SK Telecom, Kyunggi 463-784 (Korea, Republic of); Chang, Ku-Young; Hong, Dowon [Cryptography Research Team, Electronics and Telecommunications Research Institute, Daejeon 305-700 (Korea, Republic of)

    2011-12-15

    Many arbitrated quantum signature schemes implemented with the help of a trusted third party have been developed up to now. In order to guarantee unconditional security, most of them take advantage of the optimal quantum one-time encryption based on Pauli operators. However, in this paper we point out that the previous schemes provide security only against a total break attack and show in fact that there exists an existential forgery attack that can validly modify the transmitted pair of message and signature. In addition, we also provide a simple method to recover security against the proposed attack.

  5. Cryptanalysis of the Quantum Group Signature Protocols

    Science.gov (United States)

    Zhang, Ke-Jia; Sun, Ying; Song, Ting-Ting; Zuo, Hui-Juan

    2013-11-01

    Recently, the researches of quantum group signature (QGS) have attracted a lot of attentions and some typical protocols have been designed for e-payment system, e-government, e-business, etc. In this paper, we analyze the security of the quantum group signature with the example of two novel protocols. It can be seen that both of them cannot be implemented securely since the arbitrator cannot solve the disputes fairly. In order to show that, some possible attack strategies, which can be used by the malicious participants, are proposed. Moreover, the further discussions of QGS are presented finally, including some insecurity factors and improved ideas.

  6. Argo_CUDA: Exhaustive GPU based approach for motif discovery in large DNA datasets.

    Science.gov (United States)

    Vishnevsky, Oleg V; Bocharnikov, Andrey V; Kolchanov, Nikolay A

    2017-12-10

    The development of chromatin immunoprecipitation sequencing (ChIP-seq) technology has revolutionized the genetic analysis of the basic mechanisms underlying transcription regulation and led to accumulation of information about a huge amount of DNA sequences. There are a lot of web services which are currently available for de novo motif discovery in datasets containing information about DNA/protein binding. An enormous motif diversity makes their finding challenging. In order to avoid the difficulties, researchers use different stochastic approaches. Unfortunately, the efficiency of the motif discovery programs dramatically declines with the query set size increase. This leads to the fact that only a fraction of top "peak" ChIP-Seq segments can be analyzed or the area of analysis should be narrowed. Thus, the motif discovery in massive datasets remains a challenging issue. Argo_Compute Unified Device Architecture (CUDA) web service is designed to process the massive DNA data. It is a program for the detection of degenerate oligonucleotide motifs of fixed length written in 15-letter IUPAC code. Argo_CUDA is a full-exhaustive approach based on the high-performance GPU technologies. Compared with the existing motif discovery web services, Argo_CUDA shows good prediction quality on simulated sets. The analysis of ChIP-Seq sequences revealed the motifs which correspond to known transcription factor binding sites.

  7. Switch-like Transitions Insulate Network Motifs to Modularize Biological Networks.

    Science.gov (United States)

    Atay, Oguzhan; Doncic, Andreas; Skotheim, Jan M

    2016-08-01

    Cellular decisions are made by complex networks that are difficult to analyze. Although it is common to analyze smaller sub-networks known as network motifs, it is unclear whether this is valid, because these motifs are embedded in complex larger networks. Here, we address the general question of modularity by examining the S. cerevisiae pheromone response. We demonstrate that the feedforward motif controlling the cell-cycle inhibitor Far1 is insulated from cell-cycle dynamics by the positive feedback switch that drives reentry to the cell cycle. Before cells switch on positive feedback, the feedforward motif model predicts the behavior of the larger network. Conversely, after the switch, the feedforward motif is dismantled and has no discernable effect on the cell cycle. When insulation is broken, the feedforward motif no longer predicts network behavior. This work illustrates how, despite the interconnectivity of networks, the activity of motifs can be insulated by switches that generate well-defined cellular states. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. SLIDER: a generic metaheuristic for the discovery of correlated motifs in protein-protein interaction networks.

    Science.gov (United States)

    Boyen, Peter; Van Dyck, Dries; Neven, Frank; van Ham, Roeland C H J; van Dijk, Aalt D J

    2011-01-01

    Correlated motif mining (cmm) is the problem of finding overrepresented pairs of patterns, called motifs, in sequences of interacting proteins. Algorithmic solutions for cmm thereby provide a computational method for predicting binding sites for protein interaction. In this paper, we adopt a motif-driven approach where the support of candidate motif pairs is evaluated in the network. We experimentally establish the superiority of the Chi-square-based support measure over other support measures. Furthermore, we obtain that cmm is an np-hard problem for a large class of support measures (including Chi-square) and reformulate the search for correlated motifs as a combinatorial optimization problem. We then present the generic metaheuristic slider which uses steepest ascent with a neighborhood function based on sliding motifs and employs the Chi-square-based support measure. We show that slider outperforms existing motif-driven cmm methods and scales to large protein-protein interaction networks. The slider-implementation and the data used in the experiments are available on http://bioinformatics.uhasselt.be.

  9. Recurrent motifs as resonant attractor states in the narrative field: a testable model of archetype.

    Science.gov (United States)

    Goodwyn, Erik

    2013-06-01

    At the most basic level, archetypes represented Jung's attempt to explain the phenomenon of recurrent myths and folktale motifs (Jung 1956, 1959, para. 99). But the archetype remains controversial as an explanation of recurrent motifs, as the existence of recurrent motifs does not prove that archetypes exist. Thus, the challenge for contemporary archetype theory is not merely to demonstrate that recurrent motifs exist, since that is not disputed, but to demonstrate that archetypes exist and cause recurrent motifs. The present paper proposes a new model which is unlike others in that it postulates how the archetype creates resonant motifs. This model necessarily clarifies and adapts some of Jung's seminal ideas on archetype in order to provide a working framework grounded in contemporary practice and methodologies. For the first time, a model of archetype is proposed that can be validated on empirical, rather than theoretical grounds. This is achieved by linking the archetype to the hard data of recurrent motifs rather than academic trends in other fields. © 2013, The Society of Analytical Psychology.

  10. Introducing Dunaliella LIP promoter containing light-inducible motifs improves transgenic expression in Chlamydomonas reinhardtii.

    Science.gov (United States)

    Baek, Kwangryul; Lee, Yew; Nam, Onyou; Park, Seunghye; Sim, Sang Jun; Jin, EonSeon

    2016-03-01

    Promoter of the light-inducible protein gene (LIP) of Dunaliella was recently isolated in our laboratory. The aim of this work is to find the light-inducible motif in the Dunaliella LIP promoter and verify its regulatory motif with a Gaussia luciferase reporter gene transformed in Chlamydomonas reinhardtii. 400 bp upstream to the translational start site of the Dunaliella LIP gene was gradually truncated and analyzed for the luciferase expression. Furthermore, this promoter comprising duplicated or triplicated light-responsive motifs was tested for its augmentation of light response. Two putative light-responsive motifs, GT-1 binding motif and sequences over-represented in light-repressed promoters (SORLIP) located in the 200 bp LIP promoter fragment were analyzed for their light responsibility. It is turned out that SORLIP was responsible for the light-inducible activity. With the copy number of SORLIP up to three showed stronger high light response compared with the native LIP promoter fragment. Therefore, we found a light-responsive DNA motif operating in Chlamydomonas and confirm a synthetic promoter including this motif displayed light inducibility in heterologously transformed green algae for the first time. This light-inducible expression system will be applied to various area of algal research including algal biotechnology. Copyright © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. CircularLogo: A lightweight web application to visualize intra-motif dependencies.

    Science.gov (United States)

    Ye, Zhenqing; Ma, Tao; Kalmbach, Michael T; Dasari, Surendra; Kocher, Jean-Pierre A; Wang, Liguo

    2017-05-22

    The sequence logo has been widely used to represent DNA or RNA motifs for more than three decades. Despite its intelligibility and intuitiveness, the traditional sequence logo is unable to display the intra-motif dependencies and therefore is insufficient to fully characterize nucleotide motifs. Many methods have been developed to quantify the intra-motif dependencies, but fewer tools are available for visualization. We developed CircularLogo, a web-based interactive application, which is able to not only visualize the position-specific nucleotide consensus and diversity but also display the intra-motif dependencies. Applying CircularLogo to HNF6 binding sites and tRNA sequences demonstrated its ability to show intra-motif dependencies and intuitively reveal biomolecular structure. CircularLogo is implemented in JavaScript and Python based on the Django web framework. The program's source code and user's manual are freely available at http://circularlogo.sourceforge.net . CircularLogo web server can be accessed from http://bioinformaticstools.mayo.edu/circularlogo/index.html . CircularLogo is an innovative web application that is specifically designed to visualize and interactively explore intra-motif dependencies.

  12. MODA: an efficient algorithm for network motif discovery in biological networks.

    Science.gov (United States)

    Omidi, Saeed; Schreiber, Falk; Masoudi-Nejad, Ali

    2009-10-01

    In recent years, interest has been growing in the study of complex networks. Since Erdös and Rényi (1960) proposed their random graph model about 50 years ago, many researchers have investigated and shaped this field. Many indicators have been proposed to assess the global features of networks. Recently, an active research area has developed in studying local features named motifs as the building blocks of networks. Unfortunately, network motif discovery is a computationally hard problem and finding rather large motifs (larger than 8 nodes) by means of current algorithms is impractical as it demands too much computational effort. In this paper, we present a new algorithm (MODA) that incorporates techniques such as a pattern growth approach for extracting larger motifs efficiently. We have tested our algorithm and found it able to identify larger motifs with more than 8 nodes more efficiently than most of the current state-of-the-art motif discovery algorithms. While most of the algorithms rely on induced subgraphs as motifs of the networks, MODA is able to extract both induced and non-induced subgraphs simultaneously. The MODA source code is freely available at: http://LBB.ut.ac.ir/Download/LBBsoft/MODA/

  13. Network motifs in integrated cellular networks of transcription-regulation and protein-protein interaction

    Science.gov (United States)

    Yeger-Lotem, Esti; Sattath, Shmuel; Kashtan, Nadav; Itzkovitz, Shalev; Milo, Ron; Pinter, Ron Y.; Alon, Uri; Margalit, Hanah

    2004-04-01

    Genes and proteins generate molecular circuitry that enables the cell to process information and respond to stimuli. A major challenge is to identify characteristic patterns in this network of interactions that may shed light on basic cellular mechanisms. Previous studies have analyzed aspects of this network, concentrating on either transcription-regulation or protein-protein interactions. Here we search for composite network motifs: characteristic network patterns consisting of both transcription-regulation and protein-protein interactions that recur significantly more often than in random networks. To this end we developed algorithms for detecting motifs in networks with two or more types of interactions and applied them to an integrated data set of protein-protein interactions and transcription regulation in Saccharomyces cerevisiae. We found a two-protein mixed-feedback loop motif, five types of three-protein motifs exhibiting coregulation and complex formation, and many motifs involving four proteins. Virtually all four-protein motifs consisted of combinations of smaller motifs. This study presents a basic framework for detecting the building blocks of networks with multiple types of interactions.

  14. WSMD: weakly-supervised motif discovery in transcription factor ChIP-seq data.

    Science.gov (United States)

    Zhang, Hongbo; Zhu, Lin; Huang, De-Shuang

    2017-06-12

    Although discriminative motif discovery (DMD) methods are promising for eliciting motifs from high-throughput experimental data, due to consideration of computational expense, most of existing DMD methods have to choose approximate schemes that greatly restrict the search space, leading to significant loss of predictive accuracy. In this paper, we propose Weakly-Supervised Motif Discovery (WSMD) to discover motifs from ChIP-seq datasets. In contrast to the learning strategies adopted by previous DMD methods, WSMD allows a "global" optimization scheme of the motif parameters in continuous space, thereby reducing the information loss of model representation and improving the quality of resultant motifs. Meanwhile, by exploiting the connection between DMD framework and existing weakly supervised learning (WSL) technologies, we also present highly scalable learning strategies for the proposed method. The experimental results on both real ChIP-seq datasets and synthetic datasets show that WSMD substantially outperforms former DMD methods (including DREME, HOMER, XXmotif, motifRG and DECOD) in terms of predictive accuracy, while also achieving a competitive computational speed.

  15. Identification of a putative nuclear export signal motif in human NANOG homeobox domain

    Energy Technology Data Exchange (ETDEWEB)

    Park, Sung-Won; Do, Hyun-Jin; Huh, Sun-Hyung; Sung, Boreum [Department of Biomedical Science, College of Life Science, CHA University, Seongnam-si, Gyeonggi-Do (Korea, Republic of); Uhm, Sang-Jun [Department of Animal Science and Biotechnology, Sangji Youngseo College, Wonju, Gwangwon-Do (Korea, Republic of); Song, Hyuk [Department of Animal and Food Bioscience, College of Natural Science, Konkuk University, ChungJu, Chungbuk (Korea, Republic of); Kim, Nam-Hyung [Department of Animal Sciences, Chungbuk National University, Cheongju, Chungbuk (Korea, Republic of); Kim, Jae-Hwan, E-mail: jaehwan_k@cha.ac.kr [Department of Biomedical Science, College of Life Science, CHA University, Seongnam-si, Gyeonggi-Do (Korea, Republic of)

    2012-05-11

    Highlights: Black-Right-Pointing-Pointer We found the putative nuclear export signal motif within human NANOG homeodomain. Black-Right-Pointing-Pointer Leucine-rich residues are important for human NANOG homeodomain nuclear export. Black-Right-Pointing-Pointer CRM1-specific inhibitor LMB blocked the potent human NANOG NES-mediated nuclear export. -- Abstract: NANOG is a homeobox-containing transcription factor that plays an important role in pluripotent stem cells and tumorigenic cells. To understand how nuclear localization of human NANOG is regulated, the NANOG sequence was examined and a leucine-rich nuclear export signal (NES) motif ({sup 125}MQELSNILNL{sup 134}) was found in the homeodomain (HD). To functionally validate the putative NES motif, deletion and site-directed mutants were fused to an EGFP expression vector and transfected into COS-7 cells, and the localization of the proteins was examined. While hNANOG HD exclusively localized to the nucleus, a mutant with both NLSs deleted and only the putative NES motif contained (hNANOG HD-{Delta}NLSs) was predominantly cytoplasmic, as observed by nucleo/cytoplasmic fractionation and Western blot analysis as well as confocal microscopy. Furthermore, site-directed mutagenesis of the putative NES motif in a partial hNANOG HD only containing either one of the two NLS motifs led to localization in the nucleus, suggesting that the NES motif may play a functional role in nuclear export. Furthermore, CRM1-specific nuclear export inhibitor LMB blocked the hNANOG potent NES-mediated export, suggesting that the leucine-rich motif may function in CRM1-mediated nuclear export of hNANOG. Collectively, a NES motif is present in the hNANOG HD and may be functionally involved in CRM1-mediated nuclear export pathway.

  16. Colored motifs reveal computational building blocks in the C. elegans brain.

    Directory of Open Access Journals (Sweden)

    Jifeng Qian

    Full Text Available BACKGROUND: Complex networks can often be decomposed into less complex sub-networks whose structures can give hints about the functional organization of the network as a whole. However, these structural motifs can only tell one part of the functional story because in this analysis each node and edge is treated on an equal footing. In real networks, two motifs that are topologically identical but whose nodes perform very different functions will play very different roles in the network. METHODOLOGY/PRINCIPAL FINDINGS: Here, we combine structural information derived from the topology of the neuronal network of the nematode C. elegans with information about the biological function of these nodes, thus coloring nodes by function. We discover that particular colorations of motifs are significantly more abundant in the worm brain than expected by chance, and have particular computational functions that emphasize the feed-forward structure of information processing in the network, while evading feedback loops. Interneurons are strongly over-represented among the common motifs, supporting the notion that these motifs process and transduce the information from the sensor neurons towards the muscles. Some of the most common motifs identified in the search for significant colored motifs play a crucial role in the system of neurons controlling the worm's locomotion. CONCLUSIONS/SIGNIFICANCE: The analysis of complex networks in terms of colored motifs combines two independent data sets to generate insight about these networks that cannot be obtained with either data set alone. The method is general and should allow a decomposition of any complex networks into its functional (rather than topological motifs as long as both wiring and functional information is available.

  17. KI motifs of human Knl1 enhance assembly of comprehensive spindle checkpoint complexes around MELT repeats.

    Science.gov (United States)

    Krenn, Veronica; Overlack, Katharina; Primorac, Ivana; van Gerwen, Suzan; Musacchio, Andrea

    2014-01-06

    The KMN network, a ten-subunit protein complex, mediates the interaction of kinetochores with spindle microtubules and recruits spindle assembly checkpoint (SAC) constituents to halt cells in mitosis until attainment of sister chromatid biorientation. Two types of motifs in the KMN subunit Knl1 interact with SAC proteins. Lys-Ile (KI) motifs, found in vertebrates, interact with the TPR motifs of Bub1 and BubR1. Met-Glu-Leu-Thr (MELT) repeats, ubiquitous in evolution, recruit the Bub3/Bub1 complex in a phosphorylation-dependent manner. The exact contributions of KI and MELT motifs to SAC signaling and chromosome alignment are unclear. We report here that KI motifs cooperate strongly with the neighboring single MELT motif in the N-terminal 250 residues (Knl1(1-250)) of human Knl1 to seed a comprehensive assembly of SAC proteins. In cells depleted of endogenous Knl1, kinetochore-targeted Knl1(1-250) suffices to restore SAC and chromosome alignment. Individual MELT repeats outside of Knl1(1-250), which lack flanking KI motifs, establish qualitatively similar sets of interactions, but less efficiently. MELT sequences on Knl1 emerge from our analysis as the platforms on which SAC complexes become assembled. Our results show that KI motifs are enhancers of MELT function in assembling SAC signaling complexes, and that they might have evolved to limit the expansion of MELT motifs by providing a more robust mechanism of SAC signaling around a single MELT. We shed light on the mechanism of Bub1 and BubR1 recruitment and identify crucial questions for future studies. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Towards a theoretical understanding of false positives in DNA motif finding

    Directory of Open Access Journals (Sweden)

    Zia Amin

    2012-06-01

    Full Text Available Abstract Background Detection of false-positive motifs is one of the main causes of low performance in de novo DNA motif-finding methods. Despite the substantial algorithm development effort in this area, recent comprehensive benchmark studies revealed that the performance of DNA motif-finders leaves room for improvement in realistic scenarios. Results Using large-deviations theory, we derive a remarkably simple relationship that describes the dependence of false positives on dataset size for the one-occurrence per sequence motif-finding problem. As expected, we predict that false-positives can be reduced by decreasing the sequence length or by adding more sequences to the dataset. Interestingly, we find that the false-positive strength depends more strongly on the number of sequences in the dataset than it does on the sequence length, but that the dependence on the number of sequences diminishes, after which adding more sequences does not reduce the false-positive rate significantly. We compare our theoretical predictions by applying four popular motif-finding algorithms that solve the one-occurrence-per-sequence problem (MEME, the Gibbs Sampler, Weeder, and GIMSAN to simulated data that contain no motifs. We find that the dependence of false positives detected by these softwares on the motif-finding parameters is similar to that predicted by our formula. Conclusions We quantify the relationship between the sequence search space and motif-finding false-positives. Based on the simple formula we derive, we provide a number of intuitive rules of thumb that may be used to enhance motif-finding results in practice. Our results provide a theoretical advance in an important problem in computational biology.

  19. Miz-1 activates gene expression via a novel consensus DNA binding motif.

    Directory of Open Access Journals (Sweden)

    Bonnie L Barrilleaux

    Full Text Available The transcription factor Miz-1 can either activate or repress gene expression in concert with binding partners including the Myc oncoprotein. The genomic binding of Miz-1 includes both core promoters and more distal sites, but the preferred DNA binding motif of Miz-1 has been unclear. We used a high-throughput in vitro technique, Bind-n-Seq, to identify two Miz-1 consensus DNA binding motif sequences--ATCGGTAATC and ATCGAT (Mizm1 and Mizm2--bound by full-length Miz-1 and its zinc finger domain, respectively. We validated these sequences directly as high affinity Miz-1 binding motifs. Competition assays using mutant probes indicated that the binding affinity of Miz-1 for Mizm1 and Mizm2 is highly sequence-specific. Miz-1 strongly activates gene expression through the motifs in a Myc-independent manner. MEME-ChIP analysis of Miz-1 ChIP-seq data in two different cell types reveals a long motif with a central core sequence highly similar to the Mizm1 motif identified by Bind-n-Seq, validating the in vivo relevance of the findings. Miz-1 ChIP-seq peaks containing the long motif are predominantly located outside of proximal promoter regions, in contrast to peaks without the motif, which are highly concentrated within 1.5 kb of the nearest transcription start site. Overall, our results indicate that Miz-1 may be directed in vivo to the novel motif sequences we have identified, where it can recruit its specific binding partners to control gene expression and ultimately regulate cell fate.

  20. Dispom: a discriminative de-novo motif discovery tool based on the jstacs library.

    Science.gov (United States)

    Grau, Jan; Keilwagen, Jens; Gohr, André; Paponov, Ivan A; Posch, Stefan; Seifert, Michael; Strickert, Marc; Grosse, Ivo

    2013-02-01

    DNA-binding proteins are a main component of gene regulation as they activate or repress gene expression by binding to specific binding sites in target regions of genomic DNA. However, de-novo discovery of these binding sites in target regions obtained by wet-lab experiments is a challenging problem in computational biology, which has not yet been solved satisfactorily. Here, we present a detailed description and analysis of the de-novo motif discovery tool Dispom, which has been developed for finding binding sites of DNA-binding proteins that are differentially abundant in a set of target regions compared to a set of control regions. Two additional features of Dispom are its capability of modeling positional preferences of binding sites and adjusting the length of the motif in the learning process. Dispom yields an increased prediction accuracy compared to existing tools for de-novo motif discovery, suggesting that the combination of searching for differentially abundant motifs, inferring their positional distributions, and adjusting the motif lengths is beneficial for de-novo motif discovery. When applying Dispom to promoters of auxin-responsive genes and those of ABI3 target genes from Arabidopsis thaliana, we identify relevant binding motifs with pronounced positional distributions. These results suggest that learning motifs, their positional distributions, and their lengths by a discriminative learning principle may aid motif discovery from ChIP-chip and gene expression data. We make Dispom freely available as part of Jstacs, an open-source Java library that is tailored to statistical sequence analysis. To facilitate extensions of Dispom, we describe its implementation using Jstacs in this manuscript. In addition, we provide a stand-alone application of Dispom at http://www.jstacs.de/index.php/Dispom for instant use.

  1. A group signature scheme based on quantum teleportation

    Science.gov (United States)

    Wen, Xiaojun; Tian, Yuan; Ji, Liping; Niu, Xiamu

    2010-05-01

    In this paper, we present a group signature scheme using quantum teleportation. Different from classical group signature and current quantum signature schemes, which could only deliver either group signature or unconditional security, our scheme guarantees both by adopting quantum key preparation, quantum encryption algorithm and quantum teleportation. Security analysis proved that our scheme has the characteristics of group signature, non-counterfeit, non-disavowal, blindness and traceability. Our quantum group signature scheme has a foreseeable application in the e-payment system, e-government, e-business, etc.

  2. Stochastic Resonance in Neuronal Network Motifs with Ornstein-Uhlenbeck Colored Noise

    Directory of Open Access Journals (Sweden)

    Xuyang Lou

    2014-01-01

    Full Text Available We consider here the effect of the Ornstein-Uhlenbeck colored noise on the stochastic resonance of the feed-forward-loop (FFL network motif. The FFL motif is modeled through the FitzHugh-Nagumo neuron model as well as the chemical coupling. Our results show that the noise intensity and the correlation time of the noise process serve as the control parameters, which have great impacts on the stochastic dynamics of the FFL motif. We find that, with a proper choice of noise intensities and the correlation time of the noise process, the signal-to-noise ratio (SNR can display more than one peak.

  3. Discovering structural motifs using a structural alphabet: Application to magnesium-binding sites

    Directory of Open Access Journals (Sweden)

    Lim Carmay

    2007-03-01

    Full Text Available Abstract Background For many metalloproteins, sequence motifs characteristic of metal-binding sites have not been found or are so short that they would not be expected to be metal-specific. Striking examples of such metalloproteins are those containing Mg2+, one of the most versatile metal cofactors in cellular biochemistry. Even when Mg2+-proteins share insufficient sequence homology to identify Mg2+-specific sequence motifs, they may still share similarity in the Mg2+-binding site structure. However, no structural motifs characteristic of Mg2+-binding sites have been reported. Thus, our aims are (i to develop a general method for discovering structural patterns/motifs characteristic of ligand-binding sites, given the 3D protein structures, and (ii to apply it to Mg2+-proteins sharing 2+-structural motifs are identified as recurring structural patterns. Results The structural alphabet-based motif discovery method has revealed the structural preference of Mg2+-binding sites for certain local/secondary structures: compared to all residues in the Mg2+-proteins, both first and second-shell Mg2+-ligands prefer loops to helices. Even when the Mg2+-proteins share no significant sequence homology, some of them share a similar Mg2+-binding site structure: 4 Mg2+-structural motifs, comprising 21% of the binding sites, were found. In particular, one of the Mg2+-structural motifs found maps to a specific functional group, namely, hydrolases. Furthermore, 2 of the motifs were not found in non metalloproteins or in Ca2+-binding proteins. The structural motifs discovered thus capture some essential biochemical and/or evolutionary properties, and hence may be useful for discovering proteins where Mg2+ plays an important biological role. Conclusion The structural motif discovery method presented herein is general and can be applied to any set of proteins with known 3D structures. This new method is timely considering the increasing number of structures for

  4. Organizational motifs for ground squirrel cone bipolar cells

    Science.gov (United States)

    Light, Adam C.; Zhu, Yongling; Shi, Jun; Saszik, Shannon; Lindstrom, Sarah; Davidson, Laura; Li, Xiaoyu; Chiodo, Vince A.; Hauswirth, William W.; Li, Wei; DeVries, Steven H.

    2012-01-01

    In daylight vision, parallel processing starts at the cone synapse. Cone signals flow to On and Off bipolar cells, which are further divided into types according to morphology, immunocytochemistry, and function. The axons of the bipolar cell types stratify at different levels in the inner plexiform layer (IPL), and can interact with costratifying amacrine and ganglion cells. These interactions endow the ganglion cell types with unique functional properties. The wiring that underlies the interactions between bipolar, amacrine, and ganglion cells is poorly understood. It may be easier to elucidate this wiring if organizational rules can be established. We identify 13 types of cone bipolar cells in the ground squirrel, 11 of which contact contiguous cones with the possible exception of short-wavelength sensitive cones. Cells were identified by antibody labeling, tracer filling, and Golgi-like filling following transduction with an adeno-associated virus encoding for GFP. The 11 bipolar cell types displayed two organizational patterns. In the first pattern, 8-10 of the 11 types came in pairs with partially overlapping axonal stratification. Pairs shared morphological, immunocytochemical, and functional properties. The existence of similar pairs is a new motif that may have implications for how signals first diverge from a cone to bipolar cells, and then re-converge onto a costratifying ganglion cell. The second pattern is a mirror symmetric organization about the middle of the IPL involving at least 7 bipolar cell types. This anatomical symmetry may be associated with a functional symmetry in On and Off ganglion cell responses. PMID:22778006

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

    Directory of Open Access Journals (Sweden)

    Tianquan Jin

    2009-12-01

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

  6. The acoustic signature for intelligibility test words.

    Science.gov (United States)

    Weismer, G; Kent, R D; Hodge, M; Martin, R

    1988-10-01

    As part of a research program that aims to develop an explicit acoustic basis for a single-word intelligibility test, an initial attempt to characterize the formant trajectories and segment durations of seven test words produced by 30 normal speakers is described. These characterizations are referred to as "acoustic signatures." The data indicate that: (1) formant trajectories show two sex effects, namely, that females are more variable as a group than males and tend to have greater slopes for the transitional segment of the second-formant trajectories and that these effects are consistent across words; (2) Bark transformations of the frequency data do not seem to eliminate the interspeaker differences in formant trajectories, nor do they eliminate either of the sex effects described above; and (3) segment durations have different variabilities depending on the syllabic structure of the word; no sex effect was noted here. The discussion focuses on the appropriate form for the acoustic signatures, as well as factors that should be considered in selecting words for signature development. To demonstrate the potential application of these data, formant trajectory and segment duration data from 18 speakers with amyotrophic lateral sclerosis and varying degrees of dysarthria are compared to the acoustic signature for the word wax.

  7. Detection of proteolytic signatures for Parkinson's disease

    DEFF Research Database (Denmark)

    Jordal, Peter Lüttge; Dyrlund, Thomas F.; Winge, Kristian

    2016-01-01

    Aim: To investigate if idiopathic Parkinson's disease (IPD) is associated with distinct proteolytic signatures relative to non-neurodegenerative controls (NND) and patients with multiple system atrophy (MSA). Materials & methods: A subtiligase-based N-terminomics screening method was exploited...

  8. Molecular signatures of thyroid follicular neoplasia

    DEFF Research Database (Denmark)

    Borup, R.; Rossing, M.; Henao, Ricardo

    2010-01-01

    The molecular pathways leading to thyroid follicular neoplasia are incompletely understood, and the diagnosis of follicular tumors is a clinical challenge. To provide leads to the pathogenesis and diagnosis of the tumors, we examined the global transcriptome signatures of follicular thyroid...

  9. Negative obstacle detection by thermal signature

    Science.gov (United States)

    Matthies, Larry; Rankin, A.

    2003-01-01

    Detecting negative obstacles (ditches, potholes, and other depressions) is one of the most difficult problems in perception for autonomous, off-road navigation. Past work has largely relied on range imagery, because that is based on the geometry of the obstacle, is largely insensitive to illumination variables, and because there have not been other reliable alternatives. However, the visible aspect of negative obstacles shrinks rapidly with range, making them impossible to detect in time to avoid them at high speed. To relive this problem, we show that the interiors of negative obstacles generally remain warmer than the surrounding terrain throughout the night, making thermal signature a stable property for night-time negative obstacle detection. Experimental results to date have achieved detection distances 45% greater by using thermal signature than by using range data alone. Thermal signature is the first known observable with potential to reveal a deep negative obstacle without actually seeing far into it. Modeling solar illumination has potential to extend the usefulness of thermal signature through daylight hours.

  10. Exploring Signature Pedagogies in Undergraduate Leadership Education

    Science.gov (United States)

    Jenkins, Daniel M.

    2012-01-01

    This research explores the instructional strategies most frequently used by leadership educators who teach academic credit-bearing undergraduate leadership studies courses through a national survey and identifies signature pedagogies within the leadership discipline. Findings from this study suggest that class discussion--whether in the form of…

  11. SUSY with ATLAS Leptonic Signatures, Coannihilation Region

    CERN Document Server

    Comune, G

    2004-01-01

    In this work we present an initial study on how leptonic signatures can be used at ATLAS to constrain SUSY particle masses combinations for the first time in the so called "coannihilation region''. The analysis is carried out in the framework of mSUGRA constrained SUSY model using fast detector simulation and reconstruction exploiting an invariant mass endpoint technique.

  12. Practical Certificateless Aggregate Signatures From Bilinear Maps

    NARCIS (Netherlands)

    Gong, Zheng; Long, Yu; Hong, Xuan; Chen, Kefei

    2008-01-01

    In some restrictive environments, such as sensor networks, each sensor submits the newest information to the server, every message must be authenticated to immune forgery and replay attacks. But the regular signatures need to be saved and verified individually, which will heavily add the costs of

  13. VAR2CSA signatures of high Plasmodium falciparum parasitemia in the placenta.

    Directory of Open Access Journals (Sweden)

    Eduard Rovira-Vallbona

    Full Text Available Plasmodium falciparum infected erythrocytes (IE accumulate in the placenta through the interaction between Duffy-binding like (DBL domains of parasite-encoded ligand VAR2CSA and chondroitin sulphate-A (CSA receptor. Polymorphisms in these domains, including DBL2X and DBL3X, may affect their antigenicity or CSA-binding affinity, eventually increasing parasitemia and its adverse effects on pregnancy outcomes. A total of 373 DBL2X and 328 DBL3X sequences were obtained from transcripts of 20 placental isolates infecting Mozambican women, resulting in 176 DBL2X and 191 DBL3X unique sequences at the protein level. Sequence alignments were divided in segments containing combinations of correlated polymorphisms and the association of segment sequences with placental parasite density was tested using Bonferroni corrected regression models, taking into consideration the weight of each sequence in the infection. Three DBL2X and three DBL3X segments contained signatures of high parasite density (P<0.003 that were highly prevalent in the parasite population (49-91%. Identified regions included a flexible loop that contributes to DBL3X-CSA interaction and two DBL3X motifs with evidence of positive natural selection. Limited antibody responses against signatures of high parasite density among malaria-exposed pregnant women could not explain the increased placental parasitemia. These results suggest that a higher binding efficiency to CSA rather than reduced antigenicity might provide a biological advantage to parasites with high parasite density signatures in VAR2CSA. Sequences contributing to high parasitemia may be critical for the functional characterization of VAR2CSA and the development of tools against placental malaria.

  14. Comparison of metagenomic samples using sequence signatures

    Directory of Open Access Journals (Sweden)

    Jiang Bai

    2012-12-01

    Full Text Available Abstract Background Sequence signatures, as defined by the frequencies of k-tuples (or k-mers, k-grams, have been used extensively to compare genomic sequences of individual organisms, to identify cis-regulatory modules, and to study the evolution of regulatory sequences. Recently many next-generation sequencing (NGS read data sets of metagenomic samples from a variety of different environments have been generated. The assembly of these reads can be difficult and analysis methods based on mapping reads to genes or pathways are also restricted by the availability and completeness of existing databases. Sequence-signature-based methods, however, do not need the complete genomes or existing databases and thus, can potentially be very useful for the comparison of metagenomic samples using NGS read data. Still, the applications of sequence signature methods for the comparison of metagenomic samples have not been well studied. Results We studied several dissimilarity measures, including d2, d2* and d2S recently developed from our group, a measure (hereinafter noted as Hao used in CVTree developed from Hao’s group (Qi et al., 2004, measures based on relative di-, tri-, and tetra-nucleotide frequencies as in Willner et al. (2009, as well as standard lp measures between the frequency vectors, for the comparison of metagenomic samples using sequence signatures. We compared their performance using a series of extensive simulations and three real next-generation sequencing (NGS metagenomic datasets: 39 fecal samples from 33 mammalian host species, 56 marine samples across the world, and 13 fecal samples from human individuals. Results showed that the dissimilarity measure d2S can achieve superior performance when comparing metagenomic samples by clustering them into different groups as well as recovering environmental gradients affecting microbial samples. New insights into the environmental factors affecting microbial compositions in metagenomic samples

  15. Identification of putative regulatory motifs in the upstream regions of co-expressed functional groups of genes in Plasmodium falciparum

    Directory of Open Access Journals (Sweden)

    Joshi NV

    2009-01-01

    Full Text Available Abstract Background Regulation of gene expression in Plasmodium falciparum (Pf remains poorly understood. While over half the genes are estimated to be regulated at the transcriptional level, few regulatory motifs and transcription regulators have been found. Results The study seeks to identify putative regulatory motifs in the upstream regions of 13 functional groups of genes expressed in the intraerythrocytic developmental cycle of Pf. Three motif-discovery programs were used for the purpose, and motifs were searched for only on the gene coding strand. Four motifs – the 'G-rich', the 'C-rich', the 'TGTG' and the 'CACA' motifs – were identified, and zero to all four of these occur in the 13 sets of upstream regions. The 'CACA motif' was absent in functional groups expressed during the ring to early trophozoite transition. For functional groups expressed in each transition, the motifs tended to be similar. Upstream motifs in some functional groups showed 'positional conservation' by occurring at similar positions relative to the translational start site (TLS; this increases their significance as regulatory motifs. In the ribonucleotide synthesis, mitochondrial, proteasome and organellar translation machinery genes, G-rich, C-rich, CACA and TGTG motifs, respectively, occur with striking positional conservation. In the organellar translation machinery group, G-rich motifs occur close to the TLS. The same motifs were sometimes identified for multiple functional groups; differences in location and abundance of the motifs appear to ensure different modes of action. Conclusion The identification of positionally conserved over-represented upstream motifs throws light on putative regulatory elements for transcription in Pf.

  16. Forward secure digital signature for electronic medical records.

    Science.gov (United States)

    Yu, Yao-Chang; Huang, To-Yeh; Hou, Ting-Wei

    2012-04-01

    The Technology Safeguard in Health Insurance Portability and Accountability Act (HIPAA) Title II has addressed a way to maintain the integrity and non-repudiation of Electronic Medical Record (EMR). One of the important cryptographic technologies is mentioned in the ACT is digital signature; however, the ordinary digital signature (e.g. DSA, RSA, GQ...) has an inherent weakness: if the key (certificate) is updated, than all signatures, even the ones generated before the update, are no longer trustworthy. Unfortunately, the current most frequently used digital signature schemes are categorized into the ordinary digital signature scheme; therefore, the objective of this paper is to analyze the shortcoming of using ordinary digital signatures in EMR and to propose a method to use forward secure digital signature to sign EMR to ensure that the past EMR signatures remain trustworthy while the key (certificate) is updated.

  17. The ICDAR 2009 Signature Verification Competition

    NARCIS (Netherlands)

    Blankers, V.L.; Heuvel, C.E. van den; Franke, K.Y.; Vuurpijl, L.G.

    2009-01-01

    Recent results of forgery detection by implementing biometric signature verification methods are promising. At present, forensic signature verification in daily casework is performed through visual examination by trained forensic handwriting experts, without reliance on computerassisted methods.

  18. A blind digital signature scheme using elliptic curve digital signature algorithm

    OpenAIRE

    BÜTÜN, İsmail; DEMİRER, Mehmet

    2014-01-01

    In this study, we propose a blind digital signature (BDS) scheme based on the elliptic curve digital signature algorithm that increases the performance significantly. The security of our scheme is based on the difficulty of the elliptic curve discrete algorithm problem. Therefore, it offers much smaller key lengths for the desired security levels, along with much faster cryptographic processes, leading to fewer hardware and software requirements. According to our simulation results, ...

  19. The effects of extrinsic motivation on signature authorship opinions in forensic signature blind trials.

    Science.gov (United States)

    Dewhurst, Tahnee N; Found, Bryan; Ballantyne, Kaye N; Rogers, Doug

    2014-03-01

    Expertise studies in forensic handwriting examination involve comparisons of Forensic Handwriting Examiners' (FHEs) opinions with lay-persons on blind tests. All published studies of this type have reported real and demonstrable skill differences between the specialist and lay groups. However, critics have proposed that any difference shown may be indicative of a lack of motivation on the part of lay participants, rather than a real difference in skill. It has been suggested that qualified FHEs would be inherently more motivated to succeed in blinded validation trials, as their professional reputations could be at risk, should they perform poorly on the task provided. Furthermore, critics suggest that lay-persons would be unlikely to be highly motivated to succeed, as they would have no fear of negative consequences should they perform badly. In an effort to investigate this concern, a blind signature trial was designed and administered to forty lay-persons. Participants were required to compare known (exemplar) signatures of an individual to questioned signatures and asked to express an opinion regarding whether the writer of the known signatures wrote each of the questioned signatures. The questioned signatures comprised a mixture of genuine, disguised and simulated signatures. The forty participants were divided into two separate groupings. Group 'A' were requested to complete the trial as directed and were advised that for each correct answer they would be financially rewarded, for each incorrect answer they would be financially penalized, and for each inconclusive opinion they would receive neither penalty nor reward. Group 'B' was requested to complete the trial as directed, with no mention of financial recompense or penalty. The results of this study do not support the proposition that motivation rather than skill difference is the source of the statistical difference in opinions between individuals' results in blinded signature proficiency trials. Crown

  20. TrieAMD: a scalable and efficient apriori motif discovery approach.

    Science.gov (United States)

    Al-Turaiki, Isra; Badr, Ghada; Mathkour, Hassan

    2015-01-01

    Motif discovery is the problem of finding recurring patterns in biological sequences. It is one of the hardest and long-standing problems in bioinformatics. Apriori is a well-known data-mining algorithm for the discovery of frequent patterns in large datasets. In this paper, we apply the Apriori algorithm and use the Trie data structure to discover motifs. We propose several modifications so that we can adapt the classic Apriori to our problem. Experiments are conducted on Tompa's benchmark to investigate the performance of our proposed algorithm, the Trie-based Apriori Motif Discovery (TrieAMD). Results show that our algorithm outperforms all of the tested tools on real datasets for the average sensitivity measure, which means that our approach is able to discover more motifs. In terms of specificity, the performance of our algorithm is comparable to the other tools. The results also confirm both linear time and linear space scalability of the algorithm.

  1. Protospacer adjacent motif (PAM)-distal sequences engage CRISPR Cas9 DNA target cleavage

    National Research Council Canada - National Science Library

    Cencic, Regina; Miura, Hisashi; Malina, Abba; Robert, Francis; Ethier, Sylvain; Schmeing, T Martin; Dostie, Josée; Pelletier, Jerry

    2014-01-01

    ...') protospacer adjacent motifs (PAM). Yet among 43 ChIP-seq sites harboring seed regions analyzed for mutational status, we find editing only at the intended on-target locus and one off-target site...

  2. Thermal Stability of Modified i-Motif Oligonucleotides with Naphthalimide Intercalating Nucleic Acids

    DEFF Research Database (Denmark)

    El-Sayed, Ahmed Ali; Pedersen, Erik B.; Khaireldin, Nahid Y.

    2016-01-01

    of naphthalimide (1H-benzo[de]isoquinoline-1,3(2H)-dione) as the intercalating nucleic acid. The stabilities of i-motif structures with inserted naphthalimide intercalating nucleotides were studied using UV melting temperatures (Tm) and circular dichroism spectra at different pH values and conditions (crowding......In continuation of our investigation of characteristics and thermodynamic properties of the i-motif 5′-d[(CCCTAA)3CCCT)] upon insertion of intercalating nucleotides into the cytosine-rich oligonucleotide, this article evaluates the stabilities of i-motif oligonucleotides upon insertion...... and non-crowding). This study indicated a positive effect of the naphthalimide intercalating nucleotides on the stabilities of the i-motif structures compared to the wild-type structure which is in contrast to a previous observation for a pyrene-intercalating nucleotide showing a decrease in Tm values....

  3. Structure and Function of the Feed-Forward Loop Network Motif

    National Research Council Canada - National Science Library

    S. Mangan; U. Alon

    2003-01-01

    .... One of these motifs is the feed-forward loop (FFL). The FFL, a three-gene pattern, is composed of two input transcription factors, one of which regulates the other, both jointly regulating a target gene...

  4. Salt-bridge Swapping in the EXXERFXYY Motif of Proton Coupled Oligopeptide Transporters

    DEFF Research Database (Denmark)

    Aduri, Nanda G; Prabhala, Bala K; Ernst, Heidi A

    2015-01-01

    Proton-coupled oligopeptide transporters (POTs) couple the inwards transport of di- or tripeptides with an inwards-directed transport of protons. Evidence from several studies of different POTs have pointed towards involvement of a highly conserved sequence motif, E1XXE2RFXYY (from here on referred......-motif salt bridge, i.e. R-E2 to R-E1, which is consistent with previous structural studies. Molecular dynamics simulations of the motif variants E1XXE2R and E1XXQ2R support this mechanism. The simulations showed that upon changing conformation, arginine pushes Helix V, through interactions with the highly...... conserved FYING motif, further away from the central cavity, in what could be a stabilization of an inward-facing conformation. As E2 has been suggested to be the primary site for protonation, these novel findings show how protonation may drive conformational changes through interactions of two highly...

  5. A Signature Comparing Android Mobile Application Utilizing Feature Extracting Algorithms

    Directory of Open Access Journals (Sweden)

    Paul Grafilon

    2017-08-01

    Full Text Available The paper presented one of the application that can be done using smartphones camera. Nowadays forgery is one of the most undetected crimes. With the forensic technology used today it is still difficult for authorities to compare and define what a real signature is and what a forged signature is. A signature is a legal representation of a person. All transactions are based on a signature. Forgers may use a signature to sign illegal contracts and withdraw from bank accounts undetected. A signature can also be forged during election periods for repeated voting. Addressing the issues a signature should always be secure. Signature verification is a reduced problem that still poses a real challenge for researchers. The literature on signature verification is quite extensive and shows two main areas of research off-line and on-line systems. Off-line systems deal with a static image of the signature i.e. the result of the action of signing while on-line systems work on the dynamic process of generating the signature i.e. the action of signing itself. The researchers have found a way to resolve the concerns. A mobile application that integrates the camera to take a picture of a signature analyzes it and compares it to other signatures for verification. It will exist to help citizens to be more cautious and aware with issues regarding the signatures. This might also be relevant to help organizations and institutions such as banks and insurance companies in verifying signatures that may avoid unwanted transactions and identity theft. Furthermore this might help the authorities in the never ending battle against crime especially against forgers and thieves. The project aimed to design and develop a mobile application that integrates the smartphone camera for verifying and comparing signatures for security using the best algorithm possible. As the result of the development the said smartphone camera application is functional and reliable.

  6. The Verrucomicrobia LexA-binding Motif: Insights into the Evolutionary Dynamics of the SOS Response

    Directory of Open Access Journals (Sweden)

    Ivan Erill

    2016-07-01

    Full Text Available The SOS response is the primary bacterial mechanism to address DNA damage, coordinating multiple cellular processes that include DNA repair, cell division and translesion synthesis. In contrast to other regulatory systems, the composition of the SOS genetic network and the binding motif of its transcriptional repressor, LexA, have been shown to vary greatly across bacterial clades, making it an ideal system to study the co-evolution of transcription factors and their regulons. Leveraging comparative genomics approaches and prior knowledge on the core SOS regulon, here we define the binding motif of the Verrucomicrobia, a recently described phylum of emerging interest due to its association with eukaryotic hosts. Site directed mutagenesis of the Verrucomicrobium spinosum recA promoter confirms that LexA binds a 14 bp palindromic motif with consensus sequence TGTTC-N4-GAACA. Computational analyses suggest that recognition of this novel motif is determined primarily by changes in base-contacting residues of the third alpha helix of the LexA helix-turn-helix DNA binding motif. In conjunction with comparative genomics analysis of the LexA regulon in the Verrucomicrobia phylum, electrophoretic shift assays reveal that LexA binds to operators in the promoter region of DNA repair genes and a mutagenesis cassette in this organism, and identify previously unreported components of the SOS response. The identification of tandem LexA-binding sites generating instances of other LexA-binding motifs in the lexA gene promoter of Verrucomicrobia species leads us to postulate a novel mechanism for LexA-binding motif evolution. This model, based on gene duplication, successfully addresses outstanding questions in the intricate co-evolution of the LexA protein, its binding motif and the regulatory network it controls.

  7. Base motif recognition and design of DNA templates for fluorescent silver clusters by machine learning.

    Science.gov (United States)

    Copp, Stacy M; Bogdanov, Petko; Debord, Mark; Singh, Ambuj; Gwinn, Elisabeth

    2014-09-03

    Discriminative base motifs within DNA templates for fluorescent silver clusters are identified using methods that combine large experimental data sets with machine learning tools for pattern recognition. Combining the discovery of certain multibase motifs important for determining fluorescence brightness with a generative algorithm, the probability of selecting DNA templates that stabilize fluorescent silver clusters is increased by a factor of >3. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Fast motif matching revisited: high-order PWMs, SNPs and indels.

    Science.gov (United States)

    Korhonen, Janne H; Palin, Kimmo; Taipale, Jussi; Ukkonen, Esko

    2017-02-15

    While the position weight matrix (PWM) is the most popular model for sequence motifs, there is growing evidence of the usefulness of more advanced models such as first-order Markov representations, and such models are also becoming available in well-known motif databases. There has been lots of research of how to learn these models from training data but the problem of predicting putative sites of the learned motifs by matching the model against new sequences has been given less attention. Moreover, motif site analysis is often concerned about how different variants in the sequence affect the sites. So far, though, the corresponding efficient software tools for motif matching have been lacking. We develop fast motif matching algorithms for the aforementioned tasks. First, we formalize a framework based on high-order position weight matrices for generic representation of motif models with dinucleotide or general q -mer dependencies, and adapt fast PWM matching algorithms to the high-order PWM framework. Second, we show how to incorporate different types of sequence variants , such as SNPs and indels, and their combined effects into efficient PWM matching workflows. Benchmark results show that our algorithms perform well in practice on genome-sized sequence sets and are for multiple motif search much faster than the basic sliding window algorithm. Implementations are available as a part of the MOODS software package under the GNU General Public License v3.0 and the Biopython license ( http://www.cs.helsinki.fi/group/pssmfind ). janne.h.korhonen@gmail.com.

  9. CyClus3D: a Cytoscape plugin for clustering network motifs in integrated networks.

    Science.gov (United States)

    Audenaert, Pieter; Van Parys, Thomas; Brondel, Florian; Pickavet, Mario; Demeester, Piet; Van de Peer, Yves; Michoel, Tom

    2011-06-01

    Network motifs in integrated molecular networks represent functional relationships between distinct data types. They aggregate to form dense topological structures corresponding to functional modules which cannot be detected by traditional graph clustering algorithms. We developed CyClus3D, a Cytoscape plugin for clustering composite three-node network motifs using a 3D spectral clustering algorithm. Via the Cytoscape plugin manager or http://bioinformatics.psb.ugent.be/software/details/CyClus3D.

  10. An interaction-motif-based scoring function for protein-ligand docking

    Directory of Open Access Journals (Sweden)

    Xie Zhong-Ru

    2010-06-01

    Full Text Available Abstract Background A good scoring function is essential for molecular docking computations. In conventional scoring functions, energy terms modeling pairwise interactions are cumulatively summed, and the best docking solution is selected. Here, we propose to transform protein-ligand interactions into three-dimensional geometric networks, from which recurring network substructures, or network motifs, are selected and used to provide probability-ranked interaction templates with which to score docking solutions. Results A novel scoring function for protein-ligand docking, MotifScore, was developed. It is non-energy-based, and docking is, instead, scored by counting the occurrences of motifs of protein-ligand interaction networks constructed using structures of protein-ligand complexes. MotifScore has been tested on a benchmark set established by others to assess its ability to identify near-native complex conformations among a set of decoys. In this benchmark test, 84% of the highest-scored docking conformations had root-mean-square deviations (rmsds below 2.0 Å from the native conformation, which is comparable with the best of several energy-based docking scoring functions. Many of the top motifs, which comprise a multitude of chemical groups that interact simultaneously and make a highly significant contribution to MotifScore, capture recurrent interacting patterns beyond pairwise interactions. Conclusions While providing quite good docking scores, MotifScore is quite different from conventional energy-based functions. MotifScore thus represents a new, network-based approach for exploring problems associated with molecular docking.

  11. Dual-stimuli responsive i-motif/nanoflares for sensing ATP in lysosomes.

    Science.gov (United States)

    Jin, Fen; Zheng, Jing; Liu, Changhui; Yang, Sheng; Li, Yinhui; Li, Jishan; Lian, Yan; Yang, Ronghua

    2014-08-07

    A dual-stimuli responsive i-motif/nanoflare for molecule detection in lysosomes was designed. By combining the structure-switchable i-motif sequence and high recognition ability of an adenosine triphosphate (ATP) aptamer, subcellular sensing and visualization sensing of ATP in lysosomes at the subcellular level can be achieved. This general sensing technique can be applied for a broad range of cellular communication studies to improve our understanding of subcellular signaling and function.

  12. Acoustic Signature Monitoring and Management of Naval Platforms

    NARCIS (Netherlands)

    Basten, T.G.H.; Jong, C.A.F. de; Graafland, F.; Hof, J. van 't

    2015-01-01

    Acoustic signatures make naval platforms susceptible to detection by threat sensors. The variable operational conditions and lifespan of a platform cause variations in the acoustic signature. To deal with these variations, a real time signature monitoring capability is being developed, with advisory

  13. Radar micro-doppler signatures processing and applications

    CERN Document Server

    Chen, Victor C; Miceli, William J

    2014-01-01

    Radar Micro-Doppler Signatures: Processing and applications concentrates on the processing and application of radar micro-Doppler signatures in real world situations, providing readers with a good working knowledge on a variety of applications of radar micro-Doppler signatures.

  14. 36 CFR 1150.22 - Signature of documents.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Signature of documents. 1150... Documents for Proceedings on Citations § 1150.22 Signature of documents. The signature of a party, authorized officer, employee or attorney constitutes a certification that he/she has read the document, that...

  15. 21 CFR 11.200 - Electronic signature components and controls.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Electronic signature components and controls. 11.200 Section 11.200 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ELECTRONIC RECORDS; ELECTRONIC SIGNATURES Electronic Signatures § 11.200 Electronic...

  16. Peptide-binding motifs of two common equine class I MHC molecules in Thoroughbred horses.

    Science.gov (United States)

    Bergmann, Tobias; Lindvall, Mikaela; Moore, Erin; Moore, Eugene; Sidney, John; Miller, Donald; Tallmadge, Rebecca L; Myers, Paisley T; Malaker, Stacy A; Shabanowitz, Jeffrey; Osterrieder, Nikolaus; Peters, Bjoern; Hunt, Donald F; Antczak, Douglas F; Sette, Alessandro

    2017-05-01

    Quantitative peptide-binding motifs of MHC class I alleles provide a valuable tool to efficiently identify putative T cell epitopes. Detailed information on equine MHC class I alleles is still very limited, and to date, only a single equine MHC class I allele, Eqca-1*00101 (ELA-A3 haplotype), has been characterized. The present study extends the number of characterized ELA class I specificities in two additional haplotypes found commonly in the Thoroughbred breed. Accordingly, we here report quantitative binding motifs for the ELA-A2 allele Eqca-16*00101 and the ELA-A9 allele Eqca-1*00201. Utilizing analyses of endogenously bound and eluted ligands and the screening of positional scanning combinatorial libraries, detailed and quantitative peptide-binding motifs were derived for both alleles. Eqca-16*00101 preferentially binds peptides with aliphatic/hydrophobic residues in position 2 and at the C-terminus, and Eqca-1*00201 has a preference for peptides with arginine in position 2 and hydrophobic/aliphatic residues at the C-terminus. Interestingly, the Eqca-16*00101 motif resembles that of the human HLA A02-supertype, while the Eqca-1*00201 motif resembles that of the HLA B27-supertype and two macaque class I alleles. It is expected that the identified motifs will facilitate the selection of candidate epitopes for the study of immune responses in horses.

  17. Discriminative motif discovery via simulated evolution and random under-sampling.

    Directory of Open Access Journals (Sweden)

    Tao Song

    Full Text Available Conserved motifs in biological sequences are closely related to their structure and functions. Recently, discriminative motif discovery methods have attracted more and more attention. However, little attention has been devoted to the data imbalance problem, which is one of the main reasons affecting the performance of the discriminative models. In this article, a simulated evolution method is applied to solve the multi-class imbalance problem at the stage of data preprocessing, and at the stage of Hidden Markov Models (HMMs training, a random under-sampling method is introduced for the imbalance between the positive and negative datasets. It is shown that, in the task of discovering targeting motifs of nine subcellular compartments, the motifs found by our method are more conserved than the methods without considering data imbalance problem and recover the most known targeting motifs from Minimotif Miner and InterPro. Meanwhile, we use the found motifs to predict protein subcellular localization and achieve higher prediction precision and recall for the minority classes.

  18. Identifying the preferred RNA motifs and chemotypes that interact by probing millions of combinations.

    Science.gov (United States)

    Tran, Tuan; Disney, Matthew D

    2012-01-01

    RNA is an important therapeutic target but information about RNA-ligand interactions is limited. Here, we report a screening method that probes over 3,000,000 combinations of RNA motif-small molecule interactions to identify the privileged RNA structures and chemical spaces that interact. Specifically, a small molecule library biased for binding RNA was probed for binding to over 70,000 unique RNA motifs in a high throughput solution-based screen. The RNA motifs that specifically bind each small molecule were identified by microarray-based selection. In this library-versus-library or multidimensional combinatorial screening approach, hairpin loops (among a variety of RNA motifs) were the preferred RNA motif space that binds small molecules. Furthermore, it was shown that indole, 2-phenyl indole, 2-phenyl benzimidazole and pyridinium chemotypes allow for specific recognition of RNA motifs. As targeting RNA with small molecules is an extremely challenging area, these studies provide new information on RNA-ligand interactions that has many potential uses.

  19. What Determines the Assembly of Transcriptional Network Motifs in Escherichia coli?

    Science.gov (United States)

    Camas, Francisco M.; Poyatos, Juan F.

    2008-01-01

    Transcriptional networks are constituted by a collection of building blocks known as network motifs. Why do motifs appear? An adaptive model of motif emergence was recently questioned in favor of neutralist scenarios. Here, we provide a new picture of motif assembly in Escherichia coli which partially clarifies these contrasting explanations. This is based on characterizing the linkage between motifs and sensing or response specificity of their constituent transcriptional factors (TFs). We find that sensing specificity influences the distribution of autoregulation, while the tendency of a TF to establish feed-forward loops (FFLs) depends on response specificity, i.e., regulon size. Analysis of the latter pattern reveals that coregulation between large regulon-size TFs is common under a network neutral model, leading to the assembly of a great number of FFLs and bifans. In addition, neutral exclusive regulation also leads to a collection of single input modules -the fourth basic motif. On the whole, and even under the conservative neutralist scenario considered, a substantial group of regulatory structures revealed adaptive. These structures visibly function as fully-fledged working units. PMID:18987754

  20. Motif formation and industry specific topologies in the Japanese business firm network

    Science.gov (United States)

    Maluck, Julian; Donner, Reik V.; Takayasu, Hideki; Takayasu, Misako

    2017-05-01

    Motifs and roles are basic quantities for the characterization of interactions among 3-node subsets in complex networks. In this work, we investigate how the distribution of 3-node motifs can be influenced by modifying the rules of an evolving network model while keeping the statistics of simpler network characteristics, such as the link density and the degree distribution, invariant. We exemplify this problem for the special case of the Japanese Business Firm Network, where a well-studied and relatively simple yet realistic evolving network model is available, and compare the resulting motif distribution in the real-world and simulated networks. To better approximate the motif distribution of the real-world network in the model, we introduce both subgraph dependent and global additional rules. We find that a specific rule that allows only for the merging process between nodes with similar link directionality patterns reduces the observed excess of densely connected motifs with bidirectional links. Our study improves the mechanistic understanding of motif formation in evolving network models to better describe the characteristic features of real-world networks with a scale-free topology.

  1. Pipeline for the Analysis of ChIP-seq Data and New Motif Ranking Procedure

    KAUST Repository

    Ashoor, Haitham

    2011-06-01

    This thesis presents a computational methodology for ab-initio identification of transcription factor binding sites based on ChIP-seq data. This method consists of three main steps, namely ChIP-seq data processing, motif discovery and models selection. A novel method for ranking the models of motifs identified in this process is proposed. This method combines multiple factors in order to rank the provided candidate motifs. It combines the model coverage of the ChIP-seq fragments that contain motifs from which that model is built, the suitable background data made up of shuffled ChIP-seq fragments, and the p-value that resulted from evaluating the model on actual and background data. Two ChIP-seq datasets retrieved from ENCODE project are used to evaluate and demonstrate the ability of the method to predict correct TFBSs with high precision. The first dataset relates to neuron-restrictive silencer factor, NRSF, while the second one corresponds to growth-associated binding protein, GABP. The pipeline system shows high precision prediction for both datasets, as in both cases the top ranked motif closely resembles the known motifs for the respective transcription factors.

  2. RNA Bricks—a database of RNA 3D motifs and their interactions

    Science.gov (United States)

    Chojnowski, Grzegorz; Waleń, Tomasz; Bujnicki, Janusz M.

    2014-01-01

    The RNA Bricks database (http://iimcb.genesilico.pl/rnabricks), stores information about recurrent RNA 3D motifs and their interactions, found in experimentally determined RNA structures and in RNA–protein complexes. In contrast to other similar tools (RNA 3D Motif Atlas, RNA Frabase, Rloom) RNA motifs, i.e. ‘RNA bricks’ are presented in the molecular environment, in which they were determined, including RNA, protein, metal ions, water molecules and ligands. All nucleotide residues in RNA bricks are annotated with structural quality scores that describe real-space correlation coefficients with the electron density data (if available), backbone geometry and possible steric conflicts, which can be used to identify poorly modeled residues. The database is also equipped with an algorithm for 3D motif search and comparison. The algorithm compares spatial positions of backbone atoms of the user-provided query structure and of stored RNA motifs, without relying on sequence or secondary structure information. This enables the identification of local structural similarities among evolutionarily related and unrelated RNA molecules. Besides, the search utility enables searching ‘RNA bricks’ according to sequence similarity, and makes it possible to identify motifs with modified ribonucleotide residues at specific positions. PMID:24220091

  3. RNA Bricks--a database of RNA 3D motifs and their interactions.

    Science.gov (United States)

    Chojnowski, Grzegorz; Walen, Tomasz; Bujnicki, Janusz M

    2014-01-01

    The RNA Bricks database (http://iimcb.genesilico.pl/rnabricks), stores information about recurrent RNA 3D motifs and their interactions, found in experimentally determined RNA structures and in RNA-protein complexes. In contrast to other similar tools (RNA 3D Motif Atlas, RNA Frabase, Rloom) RNA motifs, i.e. 'RNA bricks' are presented in the molecular environment, in which they were determined, including RNA, protein, metal ions, water molecules and ligands. All nucleotide residues in RNA bricks are annotated with structural quality scores that describe real-space correlation coefficients with the electron density data (if available), backbone geometry and possible steric conflicts, which can be used to identify poorly modeled residues. The database is also equipped with an algorithm for 3D motif search and comparison. The algorithm compares spatial positions of backbone atoms of the user-provided query structure and of stored RNA motifs, without relying on sequence or secondary structure information. This enables the identification of local structural similarities among evolutionarily related and unrelated RNA molecules. Besides, the search utility enables searching 'RNA bricks' according to sequence similarity, and makes it possible to identify motifs with modified ribonucleotide residues at specific positions.

  4. Improved i-motif thermal stability by insertion of anthraquinone monomers

    DEFF Research Database (Denmark)

    Gouda, Alaa S; Amine, Mahasen S.; Pedersen, Erik Bjerregaard

    2017-01-01

    In order to gain insight into how to improve thermal stability of i-motifs when used in the context of biomedical and nanotechnological applications, novel anthraquinone-modified i-motifs were synthesized by insertion of 1,8-, 1,4-, 1,5- and 2,6-disubstituted anthraquinone monomers into the TAA...... loops of a 22mer cytosine-rich human telomeric DNA sequence. The influence of the four anthraquinone linkers on the i-motif thermal stability was investigated at 295 nm and pH 5.5. Anthraquinone monomers modulate the i-motif stability in a position-depending manner and the modulation also depends...... unlocked nucleic acid monomers or twisted intercalating nucleic acid. The 2,6-disubstituted anthraquinone linker replacing T10 enabled a significant increase of i-motif thermal melting by 8.2 °C. A substantial increase of 5.0 °C in i-motif thermal melting was recorded when both A6 and T16 were modified...

  5. SLiMPrints: conservation-based discovery of functional motif fingerprints in intrinsically disordered protein regions.

    Science.gov (United States)

    Davey, Norman E; Cowan, Joanne L; Shields, Denis C; Gibson, Toby J; Coldwell, Mark J; Edwards, Richard J

    2012-11-01

    Large portions of higher eukaryotic proteomes are intrinsically disordered, and abundant evidence suggests that these unstructured regions of proteins are rich in regulatory interaction interfaces. A major class of disordered interaction interfaces are the compact and degenerate modules known as short linear motifs (SLiMs). As a result of the difficulties associated with the experimental identification and validation of SLiMs, our understanding of these modules is limited, advocating the use of computational methods to focus experimental discovery. This article evaluates the use of evolutionary conservation as a discriminatory technique for motif discovery. A statistical framework is introduced to assess the significance of relatively conserved residues, quantifying the likelihood a residue will have a particular level of conservation given the conservation of the surrounding residues. The framework is expanded to assess the significance of groupings of conserved residues, a metric that forms the basis of SLiMPrints (short linear motif fingerprints), a de novo motif discovery tool. SLiMPrints identifies relatively overconstrained proximal groupings of residues within intrinsically disordered regions, indicative of putatively functional motifs. Finally, the human proteome is analysed to create a set of highly conserved putative motif instances, including a novel site on translation initiation factor eIF2A that may regulate translation through binding of eIF4E.

  6. Discovery of Novel Human Gene Regulatory Modules from Gene Co-expression and Promoter Motif Analysis.

    Science.gov (United States)

    Ma, Shisong; Snyder, Michael; Dinesh-Kumar, Savithramma P

    2017-07-17

    Deciphering gene regulatory networks requires identification of gene expression modules. We describe a novel bottom-up approach to identify gene modules regulated by cis-regulatory motifs from a human gene co-expression network. Target genes of a cis-regulatory motif were identified from the network via the motif's enrichment or biased distribution towards transcription start sites in the promoters of co-expressed genes. A gene sub-network containing the target genes was extracted and used to derive gene modules. The analysis revealed known and novel gene modules regulated by the NF-Y motif. The binding of NF-Y proteins to these modules' gene promoters were verified using ENCODE ChIP-Seq data. The analyses also identified 8,048 Sp1 motif target genes, interestingly many of which were not detected by ENCODE ChIP-Seq. These target genes assemble into house-keeping, tissues-specific developmental, and immune response modules. Integration of Sp1 modules with genomic and epigenomic data indicates epigenetic control of Sp1 targets' expression in a cell/tissue specific manner. Finally, known and novel target genes and modules regulated by the YY1, RFX1, IRF1, and 34 other motifs were also identified. The study described here provides a valuable resource to understand transcriptional regulation of various human developmental, disease, or immunity pathways.

  7. Novel protein domains and motifs in the marine planctomycete Rhodopirellula baltica.

    Science.gov (United States)

    Studholme, David J; Fuerst, John A; Bateman, Alex

    2004-07-15

    The planctomycetes are a phylum of bacteria that have a unique cell compartmentalisation and yeast-like budding cell division and peptidoglycan-less proteinaceous cell walls. We wished to further our understanding of these unique organisms at the molecular level by searching for conserved amino acid sequence motifs and domains in the proteins encoded by Rhodopirellula baltica. Using BLAST and single-linkage clustering, we have discovered several new protein domains and sequence motifs in this planctomycete. R. baltica has multiple members of the newly discovered GEFGR protein family and the ASPIC C-terminal domain family, whilst most other organisms for which whole genome sequence is available have no more than one. Many of the domains and motifs appear to be restricted to the planctomycetes. It is possible that these protein domains and motifs may have been lost or replaced in other phyla, or they may have undergone multiple duplication events in the planctomycete lineage. One of the novel motifs probably represents a novel N-terminal export signal peptide. With their unique cell biology, it may be that the planctomycete cell compartmentalisation plan in particular needs special membrane transport mechanisms. The discovery of these new domains and motifs, many of which are associated with secretion and cell-surface functions, will help to stimulate experimental work and thus enhance further understanding of this fascinating group of organisms.

  8. Leveraging cross-link modification events in CLIP-seq for motif discovery.

    Science.gov (United States)

    Bahrami-Samani, Emad; Penalva, Luiz O F; Smith, Andrew D; Uren, Philip J

    2015-01-01

    High-throughput protein-RNA interaction data generated by CLIP-seq has provided an unprecedented depth of access to the activities of RNA-binding proteins (RBPs), the key players in co- and post-transcriptional regulation of gene expression. Motif discovery forms part of the necessary follow-up data analysis for CLIP-seq, both to refine the exact locations of RBP binding sites, and to characterize them. The specific properties of RBP binding sites, and the CLIP-seq methods, provide additional information not usually present in the classic motif discovery problem: the binding site structure, and cross-linking induced events in reads. We show that CLIP-seq data contains clear secondary structure signals, as well as technology- and RBP-specific cross-link signals. We introduce Zagros, a motif discovery algorithm specifically designed to leverage this information and explore its impact on the quality of recovered motifs. Our results indicate that using both secondary structure and cross-link modifications can greatly improve motif discovery on CLIP-seq data. Further, the motifs we recover provide insight into the balance between sequence- and structure-specificity struck by RBP binding. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  9. GPUmotif: An Ultra-Fast and Energy-Efficient Motif Analysis Program Using Graphics Processing Units

    Science.gov (United States)

    Zandevakili, Pooya; Hu, Ming; Qin, Zhaohui

    2012-01-01

    Computational detection of TF binding patterns has become an indispensable tool in functional genomics research. With the rapid advance of new sequencing technologies, large amounts of protein-DNA interaction data have been produced. Analyzing this data can provide substantial insight into the mechanisms of transcriptional regulation. However, the massive amount of sequence data presents daunting challenges. In our previous work, we have developed a novel algorithm called Hybrid Motif Sampler (HMS) that enables more scalable and accurate motif analysis. Despite much improvement, HMS is still time-consuming due to the requirement to calculate matching probabilities position-by-position. Using the NVIDIA CUDA toolkit, we developed a graphics processing unit (GPU)-accelerated motif analysis program named GPUmotif. We proposed a “fragmentation" technique to hide data transfer time between memories. Performance comparison studies showed that commonly-used model-based motif scan and de novo motif finding procedures such as HMS can be dramatically accelerated when running GPUmotif on NVIDIA graphics cards. As a result, energy consumption can also be greatly reduced when running motif analysis using GPUmotif. The GPUmotif program is freely available at http://sourceforge.net/projects/gpumotif/ PMID:22662128

  10. Gene signatures in hepatocellular carcinoma (HCC).

    Science.gov (United States)

    Andrisani, Ourania M; Studach, Leo; Merle, Philippe

    2011-02-01

    Primary hepatocellular carcinoma (HCC) is a significant human cancer globally, with poor prognosis. New and efficacious therapy strategies are needed as well as new biomarkers for early detection of at-risk patients. In this review, we discuss select microarray studies of human HCCs, and propose a gene signature that has promise for clinical/translational application. This gene signature combines the proliferation cluster of genes and the hepatic cancer initiating/stem cell gene cluster for identification of HCCs with poor prognosis. Evidence from cell-based assays identifies the existence of a mechanistic link between these two gene clusters, involving the proliferation cluster gene polo-like kinase 1 (PLK1). We propose that PLK1 is a promising therapy target for HCC. Copyright © 2010 Elsevier Ltd. All rights reserved.

  11. Stochastic monotony signature and biomedical applications.

    Science.gov (United States)

    Demongeot, Jacques; Galli Carminati, Giuliana; Carminati, Federico; Rachdi, Mustapha

    2015-12-01

    We introduce a new concept, the stochastic monotony signature of a function, made of the sequence of the signs that indicate if the function is increasing or constant (sign +), or decreasing (sign -). If the function results from the averaging of successive observations with errors, the monotony sign is a random binary variable, whose density is studied under two hypotheses for the distribution of errors: uniform and Gaussian. Then, we describe a simple statistical test allowing the comparison between the monotony signatures of two functions (e.g., one observed and the other as reference) and we apply the test to four biomedical examples, coming from genetics, psychology, gerontology, and morphogenesis. Copyright © 2015 Académie des sciences. Published by Elsevier SAS. All rights reserved.

  12. Characterizing the psychophysiological signature of boredom.

    Science.gov (United States)

    Merrifield, Colleen; Danckert, James

    2014-02-01

    Research on the experience and expression of boredom is underdeveloped. The purpose of the present study was to explore the psychophysiological signature of the subjective experience of boredom. Healthy undergraduates (n = 72) viewed previously validated and standardized video clips to induce boredom, sadness, and a neutral affective state, while their heart rate (HR), skin conductance levels (SCL), and cortisol levels were measured. Boredom yielded dynamic psychophysiological responses that differed from the other emotional states. Of particular interest, the physiological signature of boredom relative to sadness was characterized by rising HR, decreased SCL, and increased cortisol levels. This pattern of results suggests that boredom may be associated with both increased arousal and difficulties with sustained attention. These findings may help to resolve divergent conceptualizations of boredom in the extant literature and, ultimately, to enhance our understanding and treatment of clinical syndromes in which self-reported boredom is a prominent symptom.

  13. Limits and signatures of relativistic spaceflight

    Science.gov (United States)

    Yurtsever, Ulvi; Wilkinson, Steven

    2018-01-01

    While special relativity imposes an absolute speed limit at the speed of light, our Universe is not empty Minkowski spacetime. The constituents that fill the interstellar/intergalactic vacuum, including the cosmic microwave background photons, impose a lower speed limit on any object travelling at relativistic velocities. Scattering of cosmic microwave photons from an ultra-relativistic object may create radiation with a characteristic signature allowing the detection of such objects at large distances.

  14. Constraining blazar physics with polarization signatures

    Science.gov (United States)

    Zhang, Haocheng; Boettcher, Markus; Li, Hui

    2016-01-01

    Blazars are active galactic nuclei whose jets are directed very close to our line of sight. They emit nonthermal-dominated emission from radio to gamma-rays, with the radio to optical emissions known to be polarized. Both radiation and polarization signatures can be strongly variable. Observations have shown that sometimes strong multiwavelength flares are accompanied by drastic polarization variations, indicating active participation of the magnetic field during flares. We have developed a 3D multi-zone time-dependent polarization-dependent radiation transfer code, which enables us to study the spectral and polarization signatures of blazar flares simultaneously. By combining this code with a Fokker-Planck nonthermal particle evolution scheme, we are able to derive simultaneous fits to time-dependent spectra, multiwavelength light curves, and time-dependent optical polarization signatures of a well-known multiwavelength flare with 180 degree polarization angle swing of the blazar 3C279. Our work shows that with detailed consideration of light travel time effects, the apparently symmetric time-dependent radiation and polarization signatures can be naturally explained by a straight, helically symmetric jet pervaded by a helical magnetic field, without the need of any asymmetric structures. Also our model suggests that the excess in the nonthermal particles during flares can originate from magnetic reconnection events, initiated by a shock propagating through the emission region. Additionally, the magnetic field should generally revert to its initial topology after the flare. We conclude that such shock-initiated magnetic reconnection event in an emission environment with relatively strong magnetic energy can be the driver of multiwavelength flares with polarization angle swings. Future statistics on such observations will constrain general features of such events, while magneto-hydrodynamic simulations will provide physical scenarios for the magnetic field evolution

  15. Digital gene expression signatures for maize development.

    Science.gov (United States)

    Eveland, Andrea L; Satoh-Nagasawa, Namiko; Goldshmidt, Alexander; Meyer, Sandra; Beatty, Mary; Sakai, Hajime; Ware, Doreen; Jackson, David

    2010-11-01

    Genome-wide expression signatures detect specific perturbations in developmental programs and contribute to functional resolution of key regulatory networks. In maize (Zea mays) inflorescences, mutations in the RAMOSA (RA) genes affect the determinacy of axillary meristems and thus alter branching patterns, an important agronomic trait. In this work, we developed and tested a framework for analysis of tag-based, digital gene expression profiles using Illumina's high-throughput sequencing technology and the newly assembled B73 maize reference genome. We also used a mutation in the RA3 gene to identify putative expression signatures specific to stem cell fate in axillary meristem determinacy. The RA3 gene encodes a trehalose-6-phosphate phosphatase and may act at the interface between developmental and metabolic processes. Deep sequencing of digital gene expression libraries, representing three biological replicate ear samples from wild-type and ra3 plants, generated 27 million 20- to 21-nucleotide reads with frequencies spanning 4 orders of magnitude. Unique sequence tags were anchored to 3'-ends of individual transcripts by DpnII and NlaIII digests, which were multiplexed during sequencing. We mapped 86% of nonredundant signature tags to the maize genome, which associated with 37,117 gene models and unannotated regions of expression. In total, 66% of genes were detected by at least nine reads in immature maize ears. We used comparative genomics to leverage existing information from Arabidopsis (Arabidopsis thaliana) and rice (Oryza sativa) in functional analyses of differentially expressed maize genes. Results from this study provide a basis for the analysis of short-read expression data in maize and resolved specific expression signatures that will help define mechanisms of action for the RA3 gene.

  16. Selection signatures in Canchim beef cattle

    OpenAIRE

    URBINATI, I.; STAFUZZA, N. B.; OLIVEIRA, M. T.; CHUD, T. C. S.; HIGA, R. H.; L.C.A. Regitano; M.M. Alencar; Buzanskas, M. E. [UNESP; MUNARI, D. P.

    2016-01-01

    Background Recent technological advances in genomics have allowed the genotyping of cattle through single nucleotide polymorphism (SNP) panels. High-density SNP panels possess greater genome coverage and are useful for the identification of conserved regions of the genome due to selection, known as selection signatures (SS). The SS are detectable by different methods, such as the extended haplotype homozygosity (EHH); and the integrated haplotype score (iHS), which is derived from the EHH. Th...

  17. Identity-Based Verifiably Encrypted Signatures without Random Oracles

    Science.gov (United States)

    Zhang, Lei; Wu, Qianhong; Qin, Bo

    Fair exchange protocol plays an important role in electronic commerce in the case of exchanging digital contracts. Verifiably encrypted signatures provide an optimistic solution to these scenarios with an off-line trusted third party. In this paper, we propose an identity-based verifiably encrypted signature scheme. The scheme is non-interactive to generate verifiably encrypted signatures and the resulting encrypted signature consists of only four group elements. Based on the computational Diffie-Hellman assumption, our scheme is proven secure without using random oracles. To the best of our knowledge, this is the first identity-based verifiably encrypted signature scheme provably secure in the standard model.

  18. A Digital Signature Scheme Based on MST3 Cryptosystems

    Directory of Open Access Journals (Sweden)

    Haibo Hong

    2014-01-01

    Full Text Available As special types of factorization of finite groups, logarithmic signature and cover have been used as the main components of cryptographic keys for secret key cryptosystems such as PGM and public key cryptosystems like MST1, MST2, and MST3. Recently, Svaba et. al proposed a revised MST3 encryption scheme with greater security. Meanwhile, they put forward an idea of constructing signature schemes on the basis of logarithmic signatures and random covers. In this paper, we firstly design a secure digital signature scheme based on logarithmic signatures and random covers. In order to complete the task, we devise a new encryption scheme based on MST3 cryptosystems.

  19. Hereditary family signature of facial expression.

    Science.gov (United States)

    Peleg, Gili; Katzir, Gadi; Peleg, Ofer; Kamara, Michal; Brodsky, Leonid; Hel-Or, Hagit; Keren, Daniel; Nevo, Eviatar

    2006-10-24

    Although facial expressions of emotion are universal, individual differences create a facial expression "signature" for each person; but, is there a unique family facial expression signature? Only a few family studies on the heredity of facial expressions have been performed, none of which compared the gestalt of movements in various emotional states; they compared only a few movements in one or two emotional states. No studies, to our knowledge, have compared movements of congenitally blind subjects with their relatives to our knowledge. Using two types of analyses, we show a correlation between movements of congenitally blind subjects with those of their relatives in think-concentrate, sadness, anger, disgust, joy, and surprise and provide evidence for a unique family facial expression signature. In the analysis "in-out family test," a particular movement was compared each time across subjects. Results show that the frequency of occurrence of a movement of a congenitally blind subject in his family is significantly higher than that outside of his family in think-concentrate, sadness, and anger. In the analysis "the classification test," in which congenitally blind subjects were classified to their families according to the gestalt of movements, results show 80% correct classification over the entire interview and 75% in anger. Analysis of the movements' frequencies in anger revealed a correlation between the movements' frequencies of congenitally blind individuals and those of their relatives. This study anticipates discovering genes that influence facial expressions, understanding their evolutionary significance, and elucidating repair mechanisms for syndromes lacking facial expression, such as autism.

  20. Measurement-device-independent quantum digital signatures

    Science.gov (United States)

    Puthoor, Ittoop Vergheese; Amiri, Ryan; Wallden, Petros; Curty, Marcos; Andersson, Erika

    2016-08-01

    Digital signatures play an important role in software distribution, modern communication, and financial transactions, where it is important to detect forgery and tampering. Signatures are a cryptographic technique for validating the authenticity and integrity of messages, software, or digital documents. The security of currently used classical schemes relies on computational assumptions. Quantum digital signatures (QDS), on the other hand, provide information-theoretic security based on the laws of quantum physics. Recent work on QDS Amiri et al., Phys. Rev. A 93, 032325 (2016);, 10.1103/PhysRevA.93.032325 Yin, Fu, and Zeng-Bing, Phys. Rev. A 93, 032316 (2016), 10.1103/PhysRevA.93.032316 shows that such schemes do not require trusted quantum channels and are unconditionally secure against general coherent attacks. However, in practical QDS, just as in quantum key distribution (QKD), the detectors can be subjected to side-channel attacks, which can make the actual implementations insecure. Motivated by the idea of measurement-device-independent quantum key distribution (MDI-QKD), we present a measurement-device-independent QDS (MDI-QDS) scheme, which is secure against all detector side-channel attacks. Based on the rapid development of practical MDI-QKD, our MDI-QDS protocol could also be experimentally implemented, since it requires a similar experimental setup.