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Sample records for adjacent motif pam

  1. An Archaeal Immune System Can Detect Multiple Protospacer Adjacent Motifs (PAMs) to Target Invader DNA*

    PubMed Central

    Fischer, Susan; Maier, Lisa-Katharina; Stoll, Britta; Brendel, Jutta; Fischer, Eike; Pfeiffer, Friedhelm; Dyall-Smith, Mike; Marchfelder, Anita

    2012-01-01

    The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated (Cas) system provides adaptive and heritable immunity against foreign genetic elements in most archaea and many bacteria. Although this system is widespread and diverse with many subtypes, only a few species have been investigated to elucidate the precise mechanisms for the defense of viruses or plasmids. Approximately 90% of all sequenced archaea encode CRISPR/Cas systems, but their molecular details have so far only been examined in three archaeal species: Sulfolobus solfataricus, Sulfolobus islandicus, and Pyrococcus furiosus. Here, we analyzed the CRISPR/Cas system of Haloferax volcanii using a plasmid-based invader assay. Haloferax encodes a type I-B CRISPR/Cas system with eight Cas proteins and three CRISPR loci for which the identity of protospacer adjacent motifs (PAMs) was unknown until now. We identified six different PAM sequences that are required upstream of the protospacer to permit target DNA recognition. This is only the second archaeon for which PAM sequences have been determined, and the first CRISPR group with such a high number of PAM sequences. Cells could survive the plasmid challenge if their CRISPR/Cas system was altered or defective, e.g. by deletion of the cas gene cassette. Experimental PAM data were supplemented with bioinformatics data on Haloferax and Haloquadratum. PMID:22767603

  2. Protospacer Adjacent Motif (PAM)-Distal Sequences Engage CRISPR Cas9 DNA Target Cleavage

    PubMed Central

    Ethier, Sylvain; Schmeing, T. Martin; Dostie, Josée; Pelletier, Jerry

    2014-01-01

    The clustered regularly interspaced short palindromic repeat (CRISPR)-associated enzyme Cas9 is an RNA-guided nuclease that has been widely adapted for genome editing in eukaryotic cells. However, the in vivo target specificity of Cas9 is poorly understood and most studies rely on in silico predictions to define the potential off-target editing spectrum. Using chromatin immunoprecipitation followed by sequencing (ChIP-seq), we delineate the genome-wide binding panorama of catalytically inactive Cas9 directed by two different single guide (sg) RNAs targeting the Trp53 locus. Cas9:sgRNA complexes are able to load onto multiple sites with short seed regions adjacent to 5′NGG3′ 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. In vitro analysis of target site recognition revealed that interactions between the 5′ end of the guide and PAM-distal target sequences are necessary to efficiently engage Cas9 nucleolytic activity, providing an explanation for why off-target editing is significantly lower than expected from ChIP-seq data. PMID:25275497

  3. Rapid characterization of CRISPR-Cas9 protospacer adjacent motif sequence elements.

    PubMed

    Karvelis, Tautvydas; Gasiunas, Giedrius; Young, Joshua; Bigelyte, Greta; Silanskas, Arunas; Cigan, Mark; Siksnys, Virginijus

    2015-01-01

    To expand the repertoire of Cas9s available for genome targeting, we present a new in vitro method for the simultaneous examination of guide RNA and protospacer adjacent motif (PAM) requirements. The method relies on the in vitro cleavage of plasmid libraries containing a randomized PAM as a function of Cas9-guide RNA complex concentration. Using this method, we accurately reproduce the canonical PAM preferences for Streptococcus pyogenes, Streptococcus thermophilus CRISPR3 (Sth3), and CRISPR1 (Sth1). Additionally, PAM and sgRNA solutions for a novel Cas9 protein from Brevibacillus laterosporus are provided by the assay and are demonstrated to support functional activity in vitro and in plants. PMID:26585795

  4. Phosphorylation at intrinsically disordered regions of PAM2 motif-containing proteins modulates their interactions with PABPC1 and influences mRNA fate.

    PubMed

    Huang, Kai-Lieh; Chadee, Amanda B; Chen, Chyi-Ying A; Zhang, Yueqiang; Shyu, Ann-Bin

    2013-03-01

    Cytoplasmic poly(A)-binding protein (PABP) C1 recruits different interacting partners to regulate mRNA fate. The majority of PABP-interacting proteins contain a PAM2 motif to mediate their interactions with PABPC1. However, little is known about the regulation of these interactions or the corresponding functional consequences. Through in silico analysis, we found that PAM2 motifs are generally embedded within an extended intrinsic disorder region (IDR) and are located next to cluster(s) of potential serine (Ser) or threonine (Thr) phosphorylation sites within the IDR. We hypothesized that phosphorylation at these Ser/Thr sites regulates the interactions between PAM2-containing proteins and PABPC1. In the present study, we have tested this hypothesis using complementary approaches to increase or decrease phosphorylation. The results indicate that changing the extent of phosphorylation of three PAM2-containing proteins (Tob2, Pan3, and Tnrc6c) alters their ability to interact with PABPC1. Results from experiments using phospho-blocking or phosphomimetic mutants in PAM2-containing proteins further support our hypothesis. Moreover, the phosphomimetic mutations appreciably affected the functions of these proteins in mRNA turnover and gene silencing. Taken together, these results provide a new framework for understanding the roles of intrinsically disordered proteins in the dynamic and signal-dependent control of cytoplasmic mRNA functions. PMID:23340509

  5. Further optimization of the M1 PAM VU0453595: Discovery of novel heterobicyclic core motifs with improved CNS penetration.

    PubMed

    Panarese, Joseph D; Cho, Hykeyung P; Adams, Jeffrey J; Nance, Kellie D; Garcia-Barrantes, Pedro M; Chang, Sichen; Morrison, Ryan D; Blobaum, Anna L; Niswender, Colleen M; Stauffer, Shaun R; Conn, P Jeffrey; Lindsley, Craig W

    2016-08-01

    This Letter describes the continued chemical optimization of the VU0453595 series of M1 positive allosteric modulators (PAMs). By surveying alternative 5,6- and 6,6-heterobicylic cores for the 6,7-dihydro-5H-pyrrolo[3,4-b]pyridine-5-one core of VU453595, we found new cores that engendered not only comparable or improved M1 PAM potency, but significantly improved CNS distribution (Kps 0.3-3.1). Moreover, this campaign provided fundamentally distinct M1 PAM chemotypes, greatly expanding the available structural diversity for this valuable CNS target, devoid of hydrogen-bond donors. PMID:27173801

  6. Identifying and Visualizing Functional PAM Diversity across CRISPR-Cas Systems.

    PubMed

    Leenay, Ryan T; Maksimchuk, Kenneth R; Slotkowski, Rebecca A; Agrawal, Roma N; Gomaa, Ahmed A; Briner, Alexandra E; Barrangou, Rodolphe; Beisel, Chase L

    2016-04-01

    CRISPR-Cas adaptive immune systems in prokaryotes boast a diversity of protein families and mechanisms of action, where most systems rely on protospacer-adjacent motifs (PAMs) for DNA target recognition. Here, we developed an in vivo, positive, and tunable screen termed PAM-SCANR (PAM screen achieved by NOT-gate repression) to elucidate functional PAMs as well as an interactive visualization scheme termed the PAM wheel to convey individual PAM sequences and their activities. PAM-SCANR and the PAM wheel identified known functional PAMs while revealing complex sequence-activity landscapes for the Bacillus halodurans I-C (Cascade), Escherichia coli I-E (Cascade), Streptococcus thermophilus II-A CRISPR1 (Cas9), and Francisella novicida V-A (Cpf1) systems. The PAM wheel was also readily applicable to existing high-throughput screens and garnered insights into SpyCas9 and SauCas9 PAM diversity. These tools offer powerful means of elucidating and visualizing functional PAMs toward accelerating our ability to understand and exploit the multitude of CRISPR-Cas systems in nature. PMID:27041224

  7. Capping motifs stabilize the leucine-rich repeat protein PP32 and rigidify adjacent repeats.

    PubMed

    Dao, Thuy P; Majumdar, Ananya; Barrick, Doug

    2014-06-01

    Capping motifs are found to flank most β-strand-containing repeat proteins. To better understand the roles of these capping motifs in organizing structure and stability, we carried out folding and solution NMR studies on the leucine-rich repeat (LRR) domain of PP32, which is composed of five tandem LRR, capped by α-helical and β-hairpin motifs on the N- and C-termini. We were able to purify PP32 constructs lacking either cap and containing destabilizing substitutions. Removing the C-cap results in complete unfolding of PP32. Removing the N-cap has a much less severe effect, decreasing stability but retaining much of its secondary structure. In contrast, the dynamics and tertiary structure of the first two repeats are significantly perturbed, based on (1)H-(15)N relaxation studies, chemical shift perturbations, and residual dipolar couplings. However, more distal repeats (3 to C-cap) retain their native tertiary structure. In this regard, the N-cap drives the folding of adjacent repeats from what appears to be a molten-globule-like state. This interpretation is supported by extensive analysis using core packing substitutions in the full-length and N-cap-truncated PP32. This work highlights the importance of caps to the stability and structural integrity of β-strand-containing LRR proteins, and emphasizes the different contributions of the N- and C-terminal caps. PMID:24659532

  8. A designed DNA binding motif that recognizes extended sites and spans two adjacent major grooves†

    PubMed Central

    Rodríguez, Jéssica; Mosquera, Jesús; García-Fandiño, Rebeca; Vázquez, M. Eugenio; Mascareñas, José L.

    2016-01-01

    We report the rational design of a DNA-binding peptide construct composed of the DNA-contacting regions of two transcription factors (GCN4 and GAGA) linked through an AT-hook DNA anchor. The resulting chimera, which represents a new, non-natural DNA binding motif, binds with high affinity and selectivity to a long composite sequence of 13 base pairs (TCAT-AATT-GAGAG). PMID:27252825

  9. Comparative Analysis of Putative Orthologues of Mitochondrial Import Motor Subunit: Pam18 and Pam16 in Plants

    PubMed Central

    Chen, Xuejin; Ghazanfar, Bushra; Khan, Abdul Rehman; Hayat, Sikandar; Cheng, Zhihui

    2013-01-01

    Pam18/Tim14 and Pam16/Tim16, highly conserved proteins among eukaryotes, are two essential subunits of protein import motors localized in the inner mitochondrial membrane. The heterodimer formed by Pam18 and Pam16 via their J-type domains serves a regulatory function in protein translocation. Here, we report that thirty-one Pam18 and twenty-six Pam16 putative orthologues in twelve plant species were identified and analyzed through bioinformatics strategy. Results data revealed that Pam18 and Pam16 were also highly conserved among plants including their J-type domains within the hydrophilic region. Key amino acid residues and an HPD motif of Pam18 were identical among the orthologues except OsPam18L5. N-myristoylation sites of Pam18 and casein kinase II phosphorylation sites of Pam 16 were more abundant, which might be important functional sites. Some Pam18 and Pam16 proteins contained a transmembrane region at the N-terminal region. Sub-cellular prediction results indicated that many orthologues localized at mitochondria. Gene expression analyses revealed that Pam18 and Pam16 in Arabidopsis might play roles in senescence and abiotic stress responses. Our detailed study provides a better understanding of Pam18 and Pam16 in plant kingdom. PMID:24194927

  10. Structural Basis for the Altered PAM Specificities of Engineered CRISPR-Cas9.

    PubMed

    Hirano, Seiichi; Nishimasu, Hiroshi; Ishitani, Ryuichiro; Nureki, Osamu

    2016-03-17

    The RNA-guided endonuclease Cas9 cleaves double-stranded DNA targets bearing a PAM (protospacer adjacent motif) and complementarity to the guide RNA. A recent study showed that, whereas wild-type Streptococcus pyogenes Cas9 (SpCas9) recognizes the 5'-NGG-3' PAM, the engineered VQR, EQR, and VRER SpCas9 variants recognize the 5'-NGA-3', 5'-NGAG-3', and 5'-NGCG-3' PAMs, respectively, thus expanding the targetable sequences in Cas9-mediated genome editing applications. Here, we present the high-resolution crystal structures of the three SpCas9 variants in complexes with a single-guide RNA and its altered PAM-containing, partially double-stranded DNA targets. A structural comparison of the three SpCas9 variants with wild-type SpCas9 revealed that the multiple mutations synergistically induce an unexpected displacement in the phosphodiester backbone of the PAM duplex, thereby allowing the SpCas9 variants to directly recognize the altered PAM nucleotides. Our findings explain the altered PAM specificities of the SpCas9 variants and establish a framework for further rational engineering of CRISPR-Cas9. PMID:26990991

  11. PAM multiplicity marks genomic target sites as inhibitory to CRISPR-Cas9 editing

    PubMed Central

    Malina, Abba; Cameron, Christopher J. F.; Robert, Francis; Blanchette, Mathieu; Dostie, Josée; Pelletier, Jerry

    2015-01-01

    In CRISPR-Cas9 genome editing, the underlying principles for selecting guide RNA (gRNA) sequences that would ensure for efficient target site modification remain poorly understood. Here we show that target sites harbouring multiple protospacer adjacent motifs (PAMs) are refractory to Cas9-mediated repair in situ. Thus we refine which substrates should be avoided in gRNA design, implicating PAM density as a novel sequence-specific feature that inhibits in vivo Cas9-driven DNA modification. PMID:26644285

  12. Exploiting the CRISPR/Cas9 PAM Constraint for Single-Nucleotide Resolution Interventions

    PubMed Central

    Li, Yi; Mendiratta, Saurabh; Ehrhardt, Kristina; Kashyap, Neha; White, Michael A.; Bleris, Leonidas

    2016-01-01

    CRISPR/Cas9 is an enabling RNA-guided technology for genome targeting and engineering. An acute DNA binding constraint of the Cas9 protein is the Protospacer Adjacent Motif (PAM). Here we demonstrate that the PAM requirement can be exploited to specifically target single-nucleotide heterozygous mutations while exerting no aberrant effects on the wild-type alleles. Specifically, we target the heterozygous G13A activating mutation of KRAS in colorectal cancer cells and we show reversal of drug resistance to a MEK small-molecule inhibitor. Our study introduces a new paradigm in genome editing and therapeutic targeting via the use of gRNA to guide Cas9 to a desired protospacer adjacent motif. PMID:26788852

  13. Engineered CRISPR-Cas9 nucleases with altered PAM specificities

    PubMed Central

    Kleinstiver, Benjamin P.; Prew, Michelle S.; Tsai, Shengdar Q.; Topkar, Ved; Nguyen, Nhu T.; Zheng, Zongli; Gonzales, Andrew P.W.; Li, Zhuyun; Peterson, Randall T.; Yeh, Jing-Ruey Joanna; Aryee, Martin J.; Joung, J. Keith

    2015-01-01

    Although CRISPR-Cas9 nucleases are widely used for genome editing1, 2, the range of sequences that Cas9 can recognize is constrained by the need for a specific protospacer adjacent motif (PAM)3–6. As a result, it can often be difficult to target double-stranded breaks (DSBs) with the precision that is necessary for various genome editing applications. The ability to engineer Cas9 derivatives with purposefully altered PAM specificities would address this limitation. Here we show that the commonly used Streptococcus pyogenes Cas9 (SpCas9) can be modified to recognize alternative PAM sequences using structural information, bacterial selection-based directed evolution, and combinatorial design. These altered PAM specificity variants enable robust editing of endogenous gene sites in zebrafish and human cells not currently targetable by wild-type SpCas9, and their genome-wide specificities are comparable to wild-type SpCas9 as judged by GUIDE-Seq analysis7. In addition, we identified and characterized another SpCas9 variant that exhibits improved specificity in human cells, possessing better discrimination against off-target sites with non-canonical NAG and NGA PAMs and/or mismatched spacers. We also found that two smaller-size Cas9 orthologues, Streptococcus thermophilus Cas9 (St1Cas9) and Staphylococcus aureus Cas9 (SaCas9), function efficiently in the bacterial selection systems and in human cells, suggesting that our engineering strategies could be extended to Cas9s from other species. Our findings provide broadly useful SpCas9 variants and, more importantly, establish the feasibility of engineering a wide range of Cas9s with altered and improved PAM specificities. PMID:26098369

  14. Engineered CRISPR-Cas9 nucleases with altered PAM specificities.

    PubMed

    Kleinstiver, Benjamin P; Prew, Michelle S; Tsai, Shengdar Q; Topkar, Ved V; Nguyen, Nhu T; Zheng, Zongli; Gonzales, Andrew P W; Li, Zhuyun; Peterson, Randall T; Yeh, Jing-Ruey Joanna; Aryee, Martin J; Joung, J Keith

    2015-07-23

    Although CRISPR-Cas9 nucleases are widely used for genome editing, the range of sequences that Cas9 can recognize is constrained by the need for a specific protospacer adjacent motif (PAM). As a result, it can often be difficult to target double-stranded breaks (DSBs) with the precision that is necessary for various genome-editing applications. The ability to engineer Cas9 derivatives with purposefully altered PAM specificities would address this limitation. Here we show that the commonly used Streptococcus pyogenes Cas9 (SpCas9) can be modified to recognize alternative PAM sequences using structural information, bacterial selection-based directed evolution, and combinatorial design. These altered PAM specificity variants enable robust editing of endogenous gene sites in zebrafish and human cells not currently targetable by wild-type SpCas9, and their genome-wide specificities are comparable to wild-type SpCas9 as judged by GUIDE-seq analysis. In addition, we identify and characterize another SpCas9 variant that exhibits improved specificity in human cells, possessing better discrimination against off-target sites with non-canonical NAG and NGA PAMs and/or mismatched spacers. We also find that two smaller-size Cas9 orthologues, Streptococcus thermophilus Cas9 (St1Cas9) and Staphylococcus aureus Cas9 (SaCas9), function efficiently in the bacterial selection systems and in human cells, suggesting that our engineering strategies could be extended to Cas9s from other species. Our findings provide broadly useful SpCas9 variants and, more importantly, establish the feasibility of engineering a wide range of Cas9s with altered and improved PAM specificities. PMID:26098369

  15. The association of a La module with the PABP-interacting motif PAM2 is a recurrent evolutionary process that led to the neofunctionalization of La-related proteins.

    PubMed

    Merret, Rémy; Martino, Luigi; Bousquet-Antonelli, Cécile; Fneich, Sara; Descombin, Julie; Billey, Elodie; Conte, Maria R; Deragon, Jean-Marc

    2013-01-01

    La-related proteins (LARPs) are largely uncharacterized factors, well conserved throughout evolution. Recent reports on the function of human LARP4 and LARP6 suggest that these proteins fulfill key functions in mRNA metabolism and/or translation. We report here a detailed evolutionary history of the LARP4 and 6 families in eukaryotes. Genes coding for LARP4 and 6 were duplicated in the common ancestor of the vertebrate lineage, but one LARP6 gene was subsequently lost in the common ancestor of the eutherian lineage. The LARP6 gene was also independently duplicated several times in the vascular plant lineage. We observed that vertebrate LARP4 and plant LARP6 duplication events were correlated with the acquisition of a PABP-interacting motif 2 (PAM2) and with a significant reorganization of their RNA-binding modules. Using isothermal titration calorimetry (ITC) and immunoprecipitation methods, we show that the two plant PAM2-containing LARP6s (LARP6b and c) can, indeed, interact with the major plant poly(A)-binding protein (PAB2), while the third plant LARP6 (LARP6a) is unable to do so. We also analyzed the RNA-binding properties and the subcellular localizations of the two types of plant LARP6 proteins and found that they display nonredundant characteristics. As a whole, our results support a model in which the acquisition by LARP4 and LARP6 of a PAM2 allowed their targeting to mRNA 3' UTRs and led to their neofunctionalization. PMID:23148093

  16. Beta-branched residues adjacent to GG4 motifs promote the efficient association of glycophorin A transmembrane helices.

    PubMed

    Cunningham, Fiona; Poulsen, Bradley E; Ip, Wilfred; Deber, Charles M

    2011-01-01

    Protein transmenembrane (TM) segments participating in helix-helix packing commonly contain small residue patterns (termed GG4 or "small-xxx-small" motifs) at i and i + 4 positions. Within many TM segments - such as the glycophorin A (GpA) sequence L75IxxGVxxGVxxT87- the G17y-xxx-Gly83 motif often occurs in combination with large, usually beta3-branched aliphatic residues at adjacent positions, typified here by Val30 and Val84 residues. To explore the importance of local P-branched character on GpA dimerization, we made systematic replacements to all 16 combinations of single or double Ile, Leu, and AIa residues at GpA TM Val/Val positions 80 and 84. Using the TOXCAT system to assay self-oligomerization in the Escherichia coli inner membrane--we observed that (i) combinations of Val and lie residues maintained, or improved dimerization levels; (ii) single Ala or Leu mutant combinations with Val or Ile maintained near-wild type dimerization affinities; and (iii) in the absence of beta-branching, i.e., Leu/Leu, Ala/Ala and Ala/Leu combinations, GpA dimerization was significantly diminished. An apparent capacity of lle-containing mutants to increase GpA dimerization versus WT likely arises from improved van der Waals packing (vs. Val) within the locus of helix contact, consistent with correlations we noted in lipid accessibility measurements. Examination of several synthetic peptides with sequences corresponding to selected GpA mutants (VV VI, IV II, and LL) confirmed their dimerization on sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE). The overall results reinforce the importance of a beta-branch-containing "ridge" residue to complement a "small-xxx-small groove" in promotion of TM-TM interactions. PMID:21072853

  17. Structural Plasticity of PAM Recognition by Engineered Variants of the RNA-Guided Endonuclease Cas9.

    PubMed

    Anders, Carolin; Bargsten, Katja; Jinek, Martin

    2016-03-17

    The RNA-guided endonuclease Cas9 from Streptococcus pyogenes (SpCas9) forms the core of a powerful genome editing technology. DNA cleavage by SpCas9 is dependent on the presence of a 5'-NGG-3' protospacer adjacent motif (PAM) in the target DNA, restricting the choice of targetable sequences. To address this limitation, artificial SpCas9 variants with altered PAM specificities have recently been developed. Here we report crystal structures of the VQR, EQR, and VRER SpCas9 variants bound to target DNAs containing their preferred PAM sequences. The structures reveal that the non-canonical PAMs are recognized by an induced fit mechanism. Besides mediating sequence-specific base recognition, the amino acid substitutions introduced in the SpCas9 variants facilitate conformational remodeling of the PAM region of the bound DNA. Guided by the structural data, we engineered a SpCas9 variant that specifically recognizes NAAG PAMs. Taken together, these studies inform further development of Cas9-based genome editing tools. PMID:26990992

  18. Broadening Staphylococcus aureus Cas9 Targeting Range by Modifying PAM Recognition

    PubMed Central

    Kleinstiver, Benjamin P.; Prew, Michelle S.; Tsai, Shengdar Q.; Nguyen, Nhu T.; Topkar, Ved V.; Zheng, Zongli; Joung, J. Keith

    2015-01-01

    CRISPR-Cas9 nucleases are primarily guided by RNA-DNA interactions but also require Cas9-mediated recognition of a protospacer adjacent motif (PAM). While potentially advantageous for specificity, extended PAM sequences limit the targeting range of Cas9 orthologues for genome editing. One possible strategy to relieve this restriction is to relax specificities for certain positions within the PAM. Here we used molecular evolution to modify the NNGRRT PAM specificity of Staphylococcus aureus Cas9 (SaCas9). One variant we identified, referred to as KKH SaCas9, shows robust genome editing activities at endogenous human target sites with NNNRRT PAMs. Importantly, using GUIDE-seq, we show that both wild-type and KKH SaCas9 induce comparable numbers of off-target effects in human cells. KKH SaCas9 increased the targeting range of SaCas9 by nearly two- to four-fold. Our molecular evolution strategy does not require structural information and therefore should be applicable to a wide range of Cas9 orthologues. PMID:26524662

  19. PAM stack test utility

    2007-08-22

    The pamtest utility calls the normal PAM hooks using a service and username supplied on the command line. This allows an administratory to test any one of many configured PAM stacks as any existing user on the machine.

  20. Structural basis for promiscuous PAM recognition in type I-E Cascade from E. coli.

    PubMed

    Hayes, Robert P; Xiao, Yibei; Ding, Fran; van Erp, Paul B G; Rajashankar, Kanagalaghatta; Bailey, Scott; Wiedenheft, Blake; Ke, Ailong

    2016-02-25

    Clustered regularly interspaced short palindromic repeats (CRISPRs) and the cas (CRISPR-associated) operon form an RNA-based adaptive immune system against foreign genetic elements in prokaryotes. Type I accounts for 95% of CRISPR systems, and has been used to control gene expression and cell fate. During CRISPR RNA (crRNA)-guided interference, Cascade (CRISPR-associated complex for antiviral defence) facilitates the crRNA-guided invasion of double-stranded DNA for complementary base-pairing with the target DNA strand while displacing the non-target strand, forming an R-loop. Cas3, which has nuclease and helicase activities, is subsequently recruited to degrade two DNA strands. A protospacer adjacent motif (PAM) sequence flanking target DNA is crucial for self versus foreign discrimination. Here we present the 2.45 Å crystal structure of Escherichia coli Cascade bound to a foreign double-stranded DNA target. The 5'-ATG PAM is recognized in duplex form, from the minor groove side, by three structural features in the Cascade Cse1 subunit. The promiscuity inherent to minor groove DNA recognition rationalizes the observation that a single Cascade complex can respond to several distinct PAM sequences. Optimal PAM recognition coincides with wedge insertion, initiating directional target DNA strand unwinding to allow segmented base-pairing with crRNA. The non-target strand is guided along a parallel path 25 Å apart, and the R-loop structure is further stabilized by locking this strand behind the Cse2 dimer. These observations provide the structural basis for understanding the PAM-dependent directional R-loop formation process. PMID:26863189

  1. Effect of P to A Mutation of the N-Terminal Residue Adjacent to the Rgd Motif on Rhodostomin: Importance of Dynamics in Integrin Recognition

    PubMed Central

    Chen, Yi-Chun; Chang, Yao-Tsung; Chang, Yung-Sheng; Huang, Chun-Hao; Chuang, Woei-Jer

    2012-01-01

    Rhodostomin (Rho) is an RGD protein that specifically inhibits integrins. We found that Rho mutants with the P48A mutation 4.4–11.5 times more actively inhibited integrin α5β1. Structural analysis showed that they have a similar 3D conformation for the RGD loop. Docking analysis also showed no difference between their interactions with integrin α5β1. However, the backbone dynamics of RGD residues were different. The values of the R2 relaxation parameter for Rho residues R49 and D51 were 39% and 54% higher than those of the P48A mutant, which caused differences in S2, Rex, and τe. The S2 values of the P48A mutant residues R49, G50, and D51 were 29%, 14%, and 28% lower than those of Rho. The Rex values of Rho residues R49 and D51 were 0.91 s−1 and 1.42 s−1; however, no Rex was found for those of the P48A mutant. The τe values of Rho residues R49 and D51 were 9.5 and 5.1 times lower than those of P48A mutant. Mutational study showed that integrin α5β1 prefers its ligands to contain (G/A)RGD but not PRGD sequences for binding. These results demonstrate that the N-terminal proline residue adjacent to the RGD motif affect its function and dynamics, which suggests that the dynamic properties of the RGD motif may be important in Rho's interaction with integrin α5β1. PMID:22238583

  2. [Unusual motifs of the nucleotide sequence adjacent to the putative transcription initiation site in the rDNA intergenic spacer of diploid wheat Triticum urartu Thum. ex Gandil, T. boeoticum Boiss, and T. monococcum L].

    PubMed

    Akhunov, E D; Chemeris, A V; Vakhitov, V A

    1997-11-01

    In the intergenic spacer (IGS) of rDNA of diploid wheats Triticum urartu, T. boeoticum, and T. monococcum, the uncommon motives adjacent to the site of transcription initiation (TIS) are revealed. They are located in the region from -6 to +1 relative to the putative TIS and are not encountered in cereals studied earlier. In T. urartu and T. boeoticum, the motif TACTATG has been revealed, in T. monococcum--TATTATG, while diploid Aegilops speltoides has the motif TATAGTA, typical of the remaining cereal species. The TIS-surrounding rDNA IGS region of diploid wheats was compared to the correspondent known rDNA IGS regions of different plant and animal species. PMID:9480224

  3. Differentiation of Pancreatic Ductal Adenocarcinoma From Chronic Pancreatitis by PAM4 Immunohistochemistry

    PubMed Central

    Shi, Chanjuan; Merchant, Nipun; Newsome, Guy; Goldenberg, David M.; Gold, David V.

    2014-01-01

    Context PAM4 is a monoclonal antibody that shows high specificity for pancreatic ductal adenocarcinoma (PDAC) and its neoplastic precursor lesions. A PAM4-based serum immunoassay is able to detect 71% of early-stage patients and 91% with advanced disease. However, approximately 20% of patients diagnosed with chronic pancreatitis (CP) are also positive for circulating PAM4 antigen. The specificity of the PAM4 antibody is critical to the interpretation of the serum-based and immunohistochemical assays for detection of PDAC. Objective To determine whether PAM4 can differentiate PDAC from nonneoplastic lesions of the pancreas. Design Tissue microarrays of PDAC (N = 43) and surgical specimens from CP (N = 32) and benign cystic lesions (N=19) were evaluated for expression of the PAM4 biomarker, MUC1, MUC4, CEACAM5/6, and CA19-9. Results PAM4 and monoclonal antibodies (MAbs) to MUC1, MUC4, CEACAM5/6, and CA19-9 were each reactive with the majority of PDAC cases; however, PAM4 was the only monoclonal antibody not to react with adjacent, nonneoplastic parenchyma. Although PAM4 labeled 19% (6 of 32) of CP specimens, reactivity was restricted to pancreatic intraepithelial neoplasia associated with CP; inflamed tissues were negative in all cases. In contrast, MUC1, MUC4, CEACAM5/6, and CA19-9 were detected in 90%, 78%, 97%, and 100% of CP, respectively, with reactivity also present in nonneoplastic inflamed tissue. Conclusions PAM4 was the only monoclonal antibody able to differentiate PDAC (and pancreatic intraepithelial neoplasia precursor lesions) from benign, nonneoplastic tissues of the pancreas. These results suggest the use of PAM4 for evaluation of tissue specimens, and support its role as an immunoassay for detection of PDAC. PMID:24476519

  4. GPM Rain Rates in Tropical Cyclone Pam

    NASA Video Gallery

    NASA-JAXA's GPM Satellite Close-up of Cyclone Pam's Rainfall NASA-JAXA's GPM core satellite captured rain rates in Tropical Cyclone Pam at 03:51 UTC (2:51 p.m. local time) on March 14, 2015. Heavie...

  5. OVERVIEW OF PAMS METEOROLOGICAL MONITORING REQUIREMENTS

    EPA Science Inventory

    The Photochemical Assessment Monitoring Station (PAMS) requires theincorporation of surface and upper air meteorological instrumentation. he platform for the surface instrumentation is a 10 m tower. he variables to be collected include horizontal wind speed, horizontal wind direc...

  6. PAMS photo image retrieval prototype alternatives analysis

    SciTech Connect

    Conner, M.L.

    1996-04-30

    Photography and Audiovisual Services uses a system called the Photography and Audiovisual Management System (PAMS) to perform order entry and billing services. The PAMS system utilizes Revelation Technologies database management software, AREV. Work is currently in progress to link the PAMS AREV system to a Microsoft SQL Server database engine to provide photograph indexing and query capabilities. The link between AREV and SQLServer will use a technique called ``bonding.`` This photograph imaging subsystem will interface to the PAMS system and handle the image capture and retrieval portions of the project. The intent of this alternatives analysis is to examine the software and hardware alternatives available to meet the requirements for this project, and identify a cost-effective solution.

  7. PAM in irrigated agriculture: Processes and soil-PAM interactions influencing canal sealing

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To identify or develop alternative polymers, which may successfully replace PAM as an irrigation reservoir or canal sealant, it is important to understand the nature of the sealing processes in these unlined, earthen irrigation structures and how PAM interacts with those processes to alter water see...

  8. Tropical cyclone Pam field survey in Vanuatu

    NASA Astrophysics Data System (ADS)

    Fritz, Hermann M.; Pilarczyk, Jessica E.; Kosciuch, Thomas; Hong, Isabel; Rarai, Allan; Harrison, Morris J.; Jockley, Fred R.; Horton, Benjamin P.

    2016-04-01

    Severe tropical cyclone Pam (Cat. 5, SSHS) crossed the Vanuatu archipelago with sustained winds of 270 km/h on March 13 and 14, 2015 and made landfall on Erromango. Pam is the most intense tropical cyclone to make landfall on Vanuatu since the advent of satellite imagery based intensity estimates in the 1970s. Pam caused one of the worst natural disaster in Vanuatu's recorded history. Eleven fatalities were directly attributed to cyclone Pam and mostly due to lack of shelter from airborne debris. On March 6 Pam formed east of the Santa Cruz Islands causing coastal inundation on Tuvalu's Vaitupu Island located some 1100 km east of the cyclone center. Pam intensified while tracking southward along Vanuatu severely affecting the Shefa and Tafea Provinces. An international storm surge reconnaissance team was deployed to Vanuatu from June 3 to 17, 2015 to complement earlier local surveys. Cyclone Pam struck a remote island archipelago particularly vulnerable to the combined cyclonic multi-hazards encompassing extreme wind gusts, massive rainfall and coastal flooding due to a combination of storm surge and storm wave impacts. The team surveyed coastal villages on Epi, the Shepherd Islands (Tongoa and Mataso), Efate (including Lelepa), Erromango, and Tanna. The survey spanned 320 km parallel to the cyclone track between Epi and Tanna encompassing more than 45 sites including the hardest hit settlements. Coastal flooding profiles were surveyed from the shoreline to the limit of inundation. Maximum coastal flood elevations and overland flow depths were measured based on water marks on buildings, scars on trees, rafted debris and corroborated with eyewitness accounts. We surveyed 91 high water marks with characteristic coastal flood levels in the 3 to 7 m range and composed of storm surge with superimposed storm waves. Inundation distances were mostly limited to a few hundred meters but reached 800 m on Epi Island. Wrack lines containing pumice perfectly delineated the

  9. Hydrodynamic Issues in PAMS Mandrel Target Fabrication

    SciTech Connect

    McQuillan, B M; Paguio, R; Subramanian, P; Takagi, M; Zebib, A

    2003-08-27

    Imperfections in PAMS mandrels critically govern the quality of final ICF targets. Imperfections in the mandrels can have a wide range of origins. Here, they present observations of 3 types of imperfections, and data to support the proposal that hydrodynamic factors during the curing of the mandrel are potential causes of these imperfections.

  10. HYDRODYNAMIC ISSUES IN PAMS MANDREL TARGET FABRICATION

    SciTech Connect

    McQUILLAN,B.W; PAGUIO,R; SUBRAMANIAN,P; TAKAGI,M; ZEBIB,A

    2003-09-01

    OAK-B135 Imperfections in PAMS mandrels critically govern the quality of final ICF targets. Imperfections in the mandrels can have a wide range of origins. Here, they present observations of 3 types of imperfections, and data to support the proposal that hydrodynamic factors during the curing of the mandrel are potential causes of these imperfections.

  11. USDA-ARS perspective on PAM

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Polyacrylamide (PAM) described herein is a synthetic organic polymer used globally by a number of important industries. It also has a number of valuable applications in irrigated agriculture, including its use in furrow irrigation to control erosion and sediment loss in runoff, manage infiltration,...

  12. Innovation in Engineering Education: The "PAMS" Project.

    ERIC Educational Resources Information Center

    Jarvis, Peter; Quick, Nick

    1995-01-01

    The University of Birmingham (England) Product and Manufacturing System (PAMS) design project is a major engineering design project undertaken by student teams and is spread over three undergraduate years. The project's objectives, open-ended student task, team member selection method, focus on transferable skills, supervision, and peer assessment…

  13. Intraoperative surgical photoacoustic microscopy (IS-PAM) using augmented reality

    NASA Astrophysics Data System (ADS)

    Lee, Changho; Han, Seunghoon; Kim, Sehui; Jeon, Mansik; Kim, Jeehyun; Kim, Chulhong

    2014-03-01

    We have developed an intraoperative surgical photoacoustic microscopy (IS-PAM) system by integrating an optical resolution photoacoustic microscopy (OR-PAM) and conventional surgical microscope. Based on the common optical path in the OR-PAM and microscope system, we can acquire the PAM and microscope images at the same time. Furthermore, by utilizing a mini-sized beam projector, 2D PAM images are back-projected onto the microscope view plane as augmented reality. Thus, both the conventional microscopic and 2D cross-sectional PAM images are displayed on the plane through an eyepiece lens of the microscope. In our method, additional image display tool is not required to show the PAM image. Therefore, it potentially offers significant convenience to surgeons without movement of their sights during surgeries. In order to demonstrate the performance of our IS-PAM system, first, we successfully monitored needle intervention in phantoms. Moreover, we successfully guided needle insertion into mice skins in vivo by visualizing surrounding blood vessels from the PAM images and the magnified skin surfaces from the conventional microscopic images simultaneously.

  14. Pro-2-PAM therapy for central and peripheral cholinesterases.

    PubMed

    Demar, James C; Clarkson, Edward D; Ratcliffe, Ruthie H; Campbell, Amy J; Thangavelu, Sonia G; Herdman, Christine A; Leader, Haim; Schulz, Susan M; Marek, Elizabeth; Medynets, Marie A; Ku, Therese C; Evans, Sarah A; Khan, Farhat A; Owens, Roberta R; Nambiar, Madhusoodana P; Gordon, Richard K

    2010-09-01

    Novel therapeutics to overcome the toxic effects of organophosphorus (OP) chemical agents are needed due to the documented use of OPs in warfare (e.g. 1980-1988 Iran/Iraq war) and terrorism (e.g. 1995 Tokyo subway attacks). Standard OP exposure therapy in the United States consists of atropine sulfate (to block muscarinic receptors), the acetylcholinesterase (AChE) reactivator (oxime) pralidoxime chloride (2-PAM), and a benzodiazepine anticonvulsant to ameliorate seizures. A major disadvantage is that quaternary nitrogen charged oximes, including 2-PAM, do not cross the blood brain barrier (BBB) to treat brain AChE. Therefore, we have synthesized and evaluated pro-2-PAM (a lipid permeable 2-PAM derivative) that can enter the brain and reactivate CNS AChE, preventing seizures in guinea pigs after exposure to OPs. The protective effects of the pro-2-PAM after OP exposure were shown using (a) surgically implanted radiotelemetry probes for electroencephalogram (EEG), (b) neurohistopathology of brain, (c) cholinesterase activities in the PNS and CNS, and (d) survivability. The PNS oxime 2-PAM was ineffective at reducing seizures/status epilepticus (SE) in diisopropylfluorophosphate (DFP)-exposed animals. In contrast, pro-2-PAM significantly suppressed and then eliminated seizure activity. In OP-exposed guinea pigs, there was a significant reduction in neurological damage with pro-2-PAM but not 2-PAM. Distinct regional areas of the brains showed significantly higher AChE activity 1.5h after OP exposure in pro-2-PAM treated animals compared to the 2-PAM treated ones. However, blood and diaphragm showed similar AChE activities in animals treated with either oxime, as both 2-PAM and pro-2-PAM are PNS active oximes. In conclusion, pro-2-PAM can cross the BBB, is rapidly metabolized inside the brain to 2-PAM, and protects against OP-induced SE through restoration of brain AChE activity. Pro-2-PAM represents the first non-invasive means of administering a CNS therapeutic for

  15. Fully Automated Data Collection Using PAM and the Development of PAM/SPACE Reversible Cassettes

    NASA Astrophysics Data System (ADS)

    Hiraki, Masahiko; Watanabe, Shokei; Chavas, Leonard M. G.; Yamada, Yusuke; Matsugaki, Naohiro; Igarashi, Noriyuki; Wakatsuki, Soichi; Fujihashi, Masahiro; Miki, Kunio; Baba, Seiki; Ueno, Go; Yamamoto, Masaki; Suzuki, Mamoru; Nakagawa, Atsushi; Watanabe, Nobuhisa; Tanaka, Isao

    2010-06-01

    To remotely control and automatically collect data in high-throughput X-ray data collection experiments, the Structural Biology Research Center at the Photon Factory (PF) developed and installed sample exchange robots PAM (PF Automated Mounting system) at PF macromolecular crystallography beamlines; BL-5A, BL-17A, AR-NW12A and AR-NE3A. We developed and installed software that manages the flow of the automated X-ray experiments; sample exchanges, loop-centering and X-ray diffraction data collection. The fully automated data collection function has been available since February 2009. To identify sample cassettes, PAM employs a two-dimensional bar code reader. New beamlines, BL-1A at the Photon Factory and BL32XU at SPring-8, are currently under construction as part of Targeted Proteins Research Program (TPRP) by the Ministry of Education, Culture, Sports, Science and Technology of Japan. However, different robots, PAM and SPACE (SPring-8 Precise Automatic Cryo-sample Exchanger), will be installed at BL-1A and BL32XU, respectively. For the convenience of the users of both facilities, pins and cassettes for PAM and SPACE are developed as part of the TPRP.

  16. Mining Conditional Phosphorylation Motifs.

    PubMed

    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/. PMID:26356863

  17. PAMS Photo Image Retrieval Prototype System Design Description

    SciTech Connect

    Conner, M.L., Westinghouse Hanford

    1996-05-02

    This System Design Description (SDD) documents the detail design of the Photo Audio/Visual Management System (PAMS) Photo Image Retrieval Prototype (PPIRP) subsystem. This SDD shows how the software is structured to satisfy the requirements identified in the PAMS Photo Image Prototype Requirements Document. It is a description of the software structure, software components,interfaces, and data that make up the PPIRP subsystem.

  18. Substance P primes lipoteichoic acid- and Pam3CysSerLys4-mediated activation of human mast cells by up-regulating Toll-like receptor 2.

    PubMed

    Tancowny, Brian P; Karpov, Victor; Schleimer, Robert P; Kulka, Marianna

    2010-10-01

    Substance P (SP) is a neuropeptide with neuroimmunoregulatory activity that may play a role in susceptibility to infection. Human mast cells, which are important in innate immune responses, were analysed for their responses to pathogen-associated molecules via Toll-like receptors (TLRs) in the presence of SP. Human cultured mast cells (LAD2) were activated by SP and TLR ligands including lipopolysaccharide (LPS), Pam3CysSerLys4 (Pam3CSK4) and lipoteichoic acid (LTA), and mast cell leukotriene and chemokine production was assessed by enzyme-linked immunosorbent assay (ELISA) and gene expression by quantitative PCR (qPCR). Mast cell degranulation was determined using a β-hexosaminidase (β-hex) assay. SP treatment of LAD2 up-regulated mRNA for TLR2, TLR4, TLR8 and TLR9 while anti-immunoglobulin E (IgE) stimulation up-regulated expression of TLR4 only. Flow cytometry and western blot confirmed up-regulation of TLR2 and TLR8. Pretreatment of LAD2 with SP followed by stimulation with Pam3CSK4 or LTA increased production of leukotriene C4 (LTC(4) ) and interleukin (IL)-8 compared with treatment with Pam3CSK4 or LTA alone (>2-fold; P<0·01). SP alone activated 5-lipoxygenase (5-LO) nuclear translocation but also augmented Pam3CSK4 and LTA-mediated 5-LO translocation. Pam3CSK4, LPS and LTA did not induce LAD2 degranulation. SP primed LTA and Pam3CSK4-mediated activation of JNK, p38 and extracellular-signal-regulated kinase (ERK) and activated the nuclear translocation of c-Jun, nuclear factor (NF)-κB, activating transcription factor 2 (ATF-2) and cyclic-AMP-responsive element binding protein (CREB) transcription factors. Pretreatment with SP followed by LTA stimulation synergistically induced production of chemokine (C-X-C motif) ligand 8 (CXCL8)/IL-8, chemokine (C-C motif) ligand 2 (CCL2)/monocyte chemotactic protein 1 (MCP-1), tumour necrosis factor (TNF) and IL-6 protein. SP primes TLR2-mediated activation of human mast cells by up-regulating TLR expression and

  19. Fast approximate motif statistics.

    PubMed

    Nicodème, P

    2001-01-01

    We present in this article a fast approximate method for computing the statistics of a number of non-self-overlapping matches of motifs in a random text in the nonuniform Bernoulli model. This method is well suited for protein motifs where the probability of self-overlap of motifs is small. For 96% of the PROSITE motifs, the expectations of occurrences of the motifs in a 7-million-amino-acids random database are computed by the approximate method with less than 1% error when compared with the exact method. Processing of the whole PROSITE takes about 30 seconds with the approximate method. We apply this new method to a comparison of the C. elegans and S. cerevisiae proteomes. PMID:11535175

  20. Development of the Patient Activation Measure for Mental Health (PAM-MH)

    PubMed Central

    Green, Carla A.; Perrin, Nancy A.; Polen, Michael R.; Leo, Michael C.; Hibbard, Judith H.; Tusler, Martin

    2012-01-01

    Objective To adapt the physical health Patient Activation Measure (PAM) for use among people with mental health conditions (PAM-MH). Research Design Data came from 3 studies among people with chronic mental health conditions and were combined in Rasch analyses. Results The PAM-MH’s psychometric properties equal those of the original 13-item PAM. Test-retest reliability and concurrent validity were good, and the PAM-MH showed sensitivity to change. Conclusions The PAM-MH appears to be a reliable and valid measure of patient activation among individuals with mental health problems. It appears to have potential for use in assessing change in activation. PMID:19728074

  1. PAMS photo image retrieval prototype system requirements specification

    SciTech Connect

    Conner, M.L.

    1996-04-30

    This project is part of the Photo Audiovisual Management System (PAMS). The project was initially identified in 1989 and has since been has been worked on under various names such as Image Retrieval and Viewing System, Photo Image Retrieval Subsystem and Image Processing and Compression System. This document builds upon the information collected and the analysis performed in the earlier phases of this project. The PAMS Photo Imaging subsystem will provide the means of capturing low resolution digital images from Photography`s negative files and associating the digital images with a record in the PAMS photo database. The digital images and key photo identification information will be accessible to HAN users to assist in locating and identifying specific photographs. After identifying desired photographs, users may request photo prints or high resolution digital images directly from Photography. The digital images captured by this project are for identification purposes only and are not intended to be of sufficient quality for subsequent use.

  2. 40 CFR 52.1080 - Photochemical Assessment Monitoring Stations (PAMS) Program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Assessment Monitoring Stations (PAMS) Program as a state implementation plan (SIP) revision, as required by... (PAMS) Program on September 11, 1995 and made it part of Maryland SIP. As with all components of the...

  3. Cristallisation, syncristallisation, et alliages moléculaires entre le lorazépam et l'oxazépam

    NASA Astrophysics Data System (ADS)

    Mascherpa-Corral, D.; Mascherpa, G.; Chauvet, A.

    1993-04-01

    Le polymorphisme et pseudopolymorphisme du lorazépam et oxazépam ont été étudiés par analyse thermique, calorimétrie différentielle à balayage et diffraction de rayons X. Deux formes polymorphes du lorazépam et plusieurs mono et hemisolvates ont été isolés à partir de recristallisation dans divers soivants. Aucun polymorphisme ni solvate n'a été mis en évidence avec l'oxazépam. Les paramètres cristallographiques des phases isolées ont été déterminées. A 160 et 203°C, le lorazépam et l'oxazépam perdent respectivement une molécule d'eau pour donner après réarrangement la quinazolinecarboxaldéhyde correspondante. La syncristallisation des deux benzodiazépines dans le benzène conduit à des alliages moléculaires à miscibilité totale à l'état solide dans tout le domaine de concentration entre l'exazépam el la forme α du lorazépam, elle n'est que partielle avec la forme β. Thermal analysis, differential scanning calorimetry, and X-ray diffraction were carried out to study the polymorphism and pseudopolymorphism of lorazepam and oxazepam. Two polymorphic forms of lorazepam and several mono- or hemisolvates were obtained after recrystallization from various solvents. No polymorphic form or solvate has been found for oxazepam. The crystallographic parameters of these new phases were determined. Lorazepam and oxazepam can lose a molecule of water at 160 and 203°C, respectively, and rearrange to quinazolinecarboxaldehyde. Mixed crystals of the two benzodiazepines, after recrystallization from benzene, lead to molecular alloys with complete solid solubility between oxazepam and the α-form of lorazepam over the whole range of composition but only to partial solubility with the β-form of lorazepam.

  4. POLYACRYLAMIDE (PAM) IN AGRICULTURE AND ENVIRONMENTAL LAND MANAGEMENT

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Anionic polyacrylamide (PAM) has been sold since 1995 to reduce irrigation-induced erosion and enhance infiltration. Its soil stabilizing and flocculating properties improve runoff water quality by reducing sediments, N, dissolved reactive P (DRP) and total P, chemical oxygen demand (COD), pesticid...

  5. Field application of PAM as an amendment in deep-tilled US southeastern Coastal Plain soils

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Polyacrylamide (PAM) was added to sandy coastal plain soils to improve physical properties and yield. Soils were amended with 8 treatments of linear and cross-linked PAMs or controls. Treatments and controls included the following: 1. spraying a 600 mg/kg solution of linear PAM behind a subsoil shan...

  6. Augmenting the spectral efficiency of enhanced PAM-DMT-based optical wireless communications.

    PubMed

    Islim, Mohamed Sufyan; Haas, Harald

    2016-05-30

    The energy efficiency of pulse-amplitude-modulated discrete multitone modulation (PAM-DMT) decreases as the modulation order of M-PAM modulation increases. Enhanced PAM-DMT (ePAM-DMT) was proposed as a solution to the reduced energy efficiency of PAM-DMT. This was achieved by allowing multiple streams of PAM-DMT to be superimposed and successively demodulated at the receiver side. In order to maintain a distortion-free unipolar ePAM-DMT system, the multiple time-domain PAM-DMT streams are required to be aligned. However, aligning the antisymmetry in ePAM-DMT is complex and results in efficiency losses. In this paper, a novel simplified method to apply the superposition modulation on M-PAM modulated discrete multitone (DMT) is introduced. Contrary to ePAM-DMT, the signal generation of the proposed system, termed augmented spectral efficiency discrete multitone (ASE-DMT), occurs in the frequency domain. This results in an improved spectral and energy efficiency. The analytical bit error rate (BER) performance bound of the proposed system is derived and compared with Monte-Carlo simulations. The system performance is shown to offer significant electrical and optical energy savings compared with ePAM-DMT and DC-biased optical orthogonal frequency division multiplexing (DCO-OFDM). PMID:27410116

  7. Adjacent segment disease.

    PubMed

    Virk, Sohrab S; Niedermeier, Steven; Yu, Elizabeth; Khan, Safdar N

    2014-08-01

    EDUCATIONAL OBJECTIVES As a result of reading this article, physicians should be able to: 1. Understand the forces that predispose adjacent cervical segments to degeneration. 2. Understand the challenges of radiographic evaluation in the diagnosis of cervical and lumbar adjacent segment disease. 3. Describe the changes in biomechanical forces applied to adjacent segments of lumbar vertebrae with fusion. 4. Know the risk factors for adjacent segment disease in spinal fusion. Adjacent segment disease (ASD) is a broad term encompassing many complications of spinal fusion, including listhesis, instability, herniated nucleus pulposus, stenosis, hypertrophic facet arthritis, scoliosis, and vertebral compression fracture. The area of the cervical spine where most fusions occur (C3-C7) is adjacent to a highly mobile upper cervical region, and this contributes to the biomechanical stress put on the adjacent cervical segments postfusion. Studies have shown that after fusion surgery, there is increased load on adjacent segments. Definitive treatment of ASD is a topic of continuing research, but in general, treatment choices are dictated by patient age and degree of debilitation. Investigators have also studied the risk factors associated with spinal fusion that may predispose certain patients to ASD postfusion, and these data are invaluable for properly counseling patients considering spinal fusion surgery. Biomechanical studies have confirmed the added stress on adjacent segments in the cervical and lumbar spine. The diagnosis of cervical ASD is complicated given the imprecise correlation of radiographic and clinical findings. Although radiological and clinical diagnoses do not always correlate, radiographs and clinical examination dictate how a patient with prolonged pain is treated. Options for both cervical and lumbar spine ASD include fusion and/or decompression. Current studies are encouraging regarding the adoption of arthroplasty in spinal surgery, but more long

  8. The mitochondrial protein translocation motor: structural conservation between the human and yeast Tim14/Pam18-Tim16/Pam16 co-chaperones.

    PubMed

    Elsner, Shira; Simian, Dana; Iosefson, Ohad; Marom, Milit; Azem, Abdussalam

    2009-05-01

    Most of our knowledge regarding the process of protein import into mitochondria has come from research employing Saccharomyces cerevisiae as a model system. Recently, several mammalian homologues of the mitochondrial motor proteins were identified. Of particular interest for us is the human Tim14/Pam18-Tim16/Pam16 complex. We chose a structural approach in order to examine the evolutionary conservation between yeast Tim14/Pam18-Tim16/Pam16 proteins and their human homologues. For this purpose, we examined the structural properties of the purified human proteins and their interaction with their yeast homologues, in vitro. Our results show that the soluble domains of the human Tim14/Pam18 and Tim16/Pam16 proteins interact with their yeast counterparts, forming heterodimeric complexes and that these complexes interact with yeast mtHsp70. PMID:19564938

  9. The Mitochondrial Protein Translocation Motor: Structural Conservation between the Human and Yeast Tim14/Pam18-Tim16/Pam16 co-Chaperones

    PubMed Central

    Elsner, Shira; Simian, Dana; Iosefson, Ohad; Marom, Milit; Azem, Abdussalam

    2009-01-01

    Most of our knowledge regarding the process of protein import into mitochondria has come from research employing Saccharomyces cerevisiae as a model system. Recently, several mammalian homologues of the mitochondrial motor proteins were identified. Of particular interest for us is the human Tim14/Pam18-Tim16/Pam16 complex. We chose a structural approach in order to examine the evolutionary conservation between yeast Tim14/Pam18-Tim16/Pam16 proteins and their human homologues. For this purpose, we examined the structural properties of the purified human proteins and their interaction with their yeast homologues, in vitro. Our results show that the soluble domains of the human Tim14/Pam18 and Tim16/Pam16 proteins interact with their yeast counterparts, forming heterodimeric complexes and that these complexes interact with yeast mtHsp70. PMID:19564938

  10. Efficient exact motif discovery

    PubMed Central

    Marschall, Tobias; Rahmann, Sven

    2009-01-01

    Motivation: 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. Results: 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. Availability and Implementation: The method has been implemented in Java. It can be obtained from http://ls11-www

  11. Motif-Role-Fingerprints: The Building-Blocks of Motifs, Clustering-Coefficients and Transitivities in Directed Networks

    PubMed Central

    McDonnell, Mark D.; Yaveroğlu, Ömer Nebil; Schmerl, Brett A.; Iannella, Nicolangelo; Ward, Lawrence M.

    2014-01-01

    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. PMID:25486535

  12. Tropical cyclone Pam coastal impact survey in Vanuatu

    NASA Astrophysics Data System (ADS)

    Fritz, H. M.; Pilarczyk, J.; Kosciuch, T. J.; Hong, I.; Rarai, A.; Harrison, M. J.; Jockley, F. R.; Horton, B.

    2015-12-01

    Severe tropical cyclone Pam (Cat. 5, SSHS) crossed the Vanuatu archipelago with sustained winds of 270 km/h on March 13 and 14, 2015 and made landfall on Erromango. Pam caused the worst natural disaster in Vanuatu's recorded history since severe tropical cyclone Uma in 1987. Eleven fatalities were directly attributed to cyclone Pam and mostly due to lack of shelter from airborne debris. On March 6 Pam formed east of the Santa Cruz Islands and intensified while tracking southward along Vanuatu severely affecting the Shefa and Tafea Provinces. An international storm surge reconnaissance team was deployed to Vanuatu from June 3 to 17, 2015 to complement earlier local surveys. Cyclone Pam struck a remote island archipelago particularly vulnerable to the combined cyclonic multi-hazards encompassing extreme wind gusts, massive rainfall and coastal flooding due to a combination of storm surge and storm wave impacts. The team surveyed coastal villages on Epi, the Shepherd Islands (Tongoa and Mataso), Efate (including Lelepa), Erromango, and Tanna. The survey spanned 320 km parallel to the cyclone track between Epi and Tanna encompassing more than 45 sites including the hardest hit settlements. Coastal flooding profiles were surveyed from the shoreline to the limit of inundation. Maximum coastal flood elevations and overland flow depths were measured based on water marks on buildings, scars on trees, rafted debris and corroborated with eyewitness accounts. We surveyed 91 high water marks with characteristic coastal flood levels in the 3 to 7 m range and composed of storm surge with superimposed storm waves. Inundation distances were mostly limited to a few hundred meters. Coral boulders of more than 1 m diameter were measured on Erromango and sediment samples were collected at key sites across the archipelago. Infrastructure damage on traditional and modern structures was assessed. Eyewitnesses were interviewed at most sites to document the chronology of the wind and

  13. [Personal motif in art].

    PubMed

    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. PMID:26202617

  14. First clinical trials of the Twente photoacoustic mammoscope (PAM)

    NASA Astrophysics Data System (ADS)

    Vaartjes, Susanne E.; van Hespen, Johan C. G.; Klaase, Joost M.; van den Engh, Frank M.; Thé, Andy K. H.; Steenbergen, Wiendelt; van Leeuwen, Ton G.; Manohar, Srirang

    2007-07-01

    Breast cancer dominates cancers in females. This burden on society and the room for improvements in the current practice of mammography have been stimuli for developing new modalities like photoacoustic mammography. At the University of Twente (UT), an instrument had been developed aimed at performing limited area scans on the human breast. This instrument is called the Twente Photoacoustic Mammoscope (PAM). The PAM is based on generating laserinduced ultrasound from absorbing structures in the breast. The heart of the instrument is a flat PVDF based detector matrix comprising 590 active elements. We show the performance characteristics of the ultrasound detector. The exciting source is an Nd:YAG laser operating at 1064 nm with 5 ns pulses. A study protocol was designed to explore the feasibility of using the PAM to detect cancer in the breasts of patients. The protocol was executed at the Medisch Spectrum Twente by using the mammoscope to obtain photoacoustic region-of-interest (ROI) images of the suspect/symptomatic breasts. We compare the photoacoustic images obtained with x-ray mammograms and ultrasound images. We show photoacoustic images of ROI in one case where we attribute high intensity regions to tumor vascularization.

  15. The Pam18/Tim14-Pam16/Tim16 complex of the mitochondrial translocation motor: the formation of a stable complex from marginally stable proteins.

    PubMed

    Iosefson, Ohad; Levy, Ran; Marom, Milit; Slutsky-Leiderman, Olga; Azem, Abdussalam

    2007-02-01

    The vast majority of mitochondrial proteins are imported from the cytosol. For matrix-localized proteins, the final step of translocation across the inner membrane is mediated by the mitochondrial translocation motor, of which mhsp70 is a key component. The ATP-dependent function of mhsp70 is regulated by a complex, composed of a J-protein (called Pam18 or Tim14) and a J-like protein (called Pam16 or Tim16), and the nucleotide exchange factor Mge1. In this study, we investigated the structural properties of a recombinant purified Pam18/Tim14-Pam16/Tim16 complex using cross-linking with the bifunctional reagent DSS and CD-spectroscopy. The results of the study show that both Pam18/Tim14 and Pam16/Tim16 are thermally unstable proteins that unfold at very low temperatures (T(m) values of 16.5 degrees C and 29 degrees C, respectively). Upon mixing the proteins in vitro, or when both proteins are co-overexpressed in bacteria, Pam18/Tim14 and Pam16/Tim16 form a heterodimer that is thermally more stable than the individual proteins (T(m) = 41 degrees C). Analysis of the properties of the complex in GdnHCl shows that dissociation of the heterodimer is the limiting step in achieving full denaturation. PMID:17242434

  16. The Pam18/Tim14–Pam16/Tim16 complex of the mitochondrial translocation motor: The formation of a stable complex from marginally stable proteins

    PubMed Central

    Iosefson, Ohad; Levy, Ran; Marom, Milit; Slutsky-Leiderman, Olga; Azem, Abdussalam

    2007-01-01

    The vast majority of mitochondrial proteins are imported from the cytosol. For matrix-localized proteins, the final step of translocation across the inner membrane is mediated by the mitochondrial translocation motor, of which mhsp70 is a key component. The ATP-dependent function of mhsp70 is regulated by a complex, composed of a J-protein (called Pam18 or Tim14) and a J-like protein (called Pam16 or Tim16), and the nucleotide exchange factor Mge1. In this study, we investigated the structural properties of a recombinant purified Pam18/Tim14–Pam16/Tim16 complex using cross-linking with the bifunctional reagent DSS and CD-spectroscopy. The results of the study show that both Pam18/Tim14 and Pam16/Tim16 are thermally unstable proteins that unfold at very low temperatures (Tm values of 16.5°C and 29°C, respectively). Upon mixing the proteins in vitro, or when both proteins are co-overexpressed in bacteria, Pam18/Tim14 and Pam16/Tim16 form a heterodimer that is thermally more stable than the individual proteins (Tm = 41°C). Analysis of the properties of the complex in GdnHCl shows that dissociation of the heterodimer is the limiting step in achieving full denaturation. PMID:17242434

  17. The Role of PAM4 in the Management of Pancreatic Cancer: Diagnosis, Radioimmunodetection, and Radioimmunotherapy

    PubMed Central

    Han, Suxia; Jin, Guihua; Wang, Lijuan; Li, Meng; He, Chenchen; Guo, Xijing; Zhu, Qing

    2014-01-01

    PAM4, a new monoclonal antibody (MAb) known as clivatuzumab, is highly reactive with pancreatic cancer and precursor lesions. It is absent from the normal tissues and has limited reactivity with nonpancreatic cancer. The detailed characteristic of the PAM4 epitope is unknown but recent studies have shown that it is dependent on MUC1 glycosylation status. The limited PAM4 expression pattern makes it an attractive candidate for management of pancreatic adenocarcinoma. In addition, PAM4 is a serum biomarker for diagnosis of pancreatic cancer. Several different radiolabeled immunodiagnostic and immunotherapeutic agents of PAM4 have been developed and some are being evaluated in preclinical and/or clinical studies. The review will focus on PAM4 and its potential utility for the diagnosis, radioimmunodetection, and radioimmunotherapy of pancreatic cancer. PMID:24818166

  18. Mining protein sequences for motifs.

    PubMed

    Narasimhan, Giri; Bu, Changsong; Gao, Yuan; Wang, Xuning; Xu, Ning; Mathee, Kalai

    2002-01-01

    We use methods from Data Mining and Knowledge Discovery to design an algorithm for detecting motifs in protein sequences. The algorithm assumes that a motif is constituted by the presence of a "good" combination of residues in appropriate locations of the motif. The algorithm attempts to compile such good combinations into a "pattern dictionary" by processing an aligned training set of protein sequences. The dictionary is subsequently used to detect motifs in new protein sequences. Statistical significance of the detection results are ensured by statistically determining the various parameters of the algorithm. Based on this approach, we have implemented a program called GYM. The Helix-Turn-Helix motif was used as a model system on which to test our program. The program was also extended to detect Homeodomain motifs. The detection results for the two motifs compare favorably with existing programs. In addition, the GYM program provides a lot of useful information about a given protein sequence. PMID:12487759

  19. PAM and Copper – a Gene/Nutrient Interaction Critical to Nervous System Function

    PubMed Central

    Bousquet-Moore, Danielle; Mains, Richard E.; Eipper, Betty A.

    2013-01-01

    Peptidylgycine α-amidating monooxygenase (PAM), a highly conserved copper-dependent enzyme, is essential for the synthesis of all amidated neuropeptides. Biophysical studies revealed that the binding of copper to PAM affects its structure, and cell biological studies demonstrated that the endocytic trafficking of PAM was sensitive to copper. We review data indicating that genetic reduction of PAM expression and mild copper deficiency in mice cause similar alterations in several physiological functions known to be regulated by neuropeptides - thermal regulation, seizure sensitivity and anxiety-like behavior. PMID:20648645

  20. Laboratory Studies to Examine the Impact of Polyacrylamide (PAM) on Soil Hydraulic Conductivity

    NASA Astrophysics Data System (ADS)

    Moran, E. A.; Young, M. H.; Yu, Z.

    2005-12-01

    Polyacrylamide (PAM) is a long-chain synthetic polymer made of the monomer acrylamide (AMD). PAM has numerous uses ranging from food processing to drilling to wastewater treatment. More recently it has been proposed as a canal sealant in the western US to improve water conservation. To support a larger field-based experimental program being implemented in Grand Junction, CO, soil column experiments are being conducted to evaluate the mechanisms of how, and to what extent, PAM reduces soil hydraulic conductivity. The goal of the experiments is to find the optimum concentration and application method of PAM that reduces hydraulic conductivity to the greatest extent. Column tests were conducted, in triplicate, using a constant head method in acrylic columns of 15 cm length and 6.4 cm diameter. An unbalanced multi-factorial design was used with experimental variables including soil type (medium silica sand, locally-derived sand, and locally-derived loam), PAM concentration (11, 22, 44, 88 kg/canal-ha), turbidity (0, 100, 350 NTU), and application method (hydrated PAM on dry soil and powdered PAM applied to water column above saturated soil). Non-crosslinked anionic PAM with a molecular weight of 12 to 24 Mg/mol was used for all experiments. Additional experiments were conducted in graduated cylinders to evaluate interactions between PAM, turbidity and water chemistry. Results of the laboratory tests will be presented and discussed in the context of water conservation in the western US.

  1. Analysis of the Performance of a PAM/PPM/OOK System Operating with OCDMA, under Nonlinear Optical Effects in Optical Fiber Propagation

    NASA Astrophysics Data System (ADS)

    Correia, D. G.; Sales, J. C.; Pinto, P. V. F.; Moura, L. P.; Ferreira, A. C.; Menezes, J. W. M.; Guimarães, G. F.; Sombra, A. S. B.

    2016-06-01

    In this article, we present a numerical simulation study of encoding, decoding and propagation performance of short optical pulses and words with modulations OOK, PAM and PPM in OCDMA systems (Optical Code Division Multiple Access). The encoding and decoding of short pulses are obtained through fiber Bragg grating(FBG - FBG optical) devices, where the codes are inserted through discrete jumps in the optical phase (±π) where Gold codes were used. A figure of merit (SNR - Signal to Noise Ratio) was obtained to quantify the interference in propagation of short optical pulses. An increase in the temporal width was observed. For decoded pulses due to the nonlinearity effect, we observed an increase of 1.3 ps considering the propagation with γ=3 W-1 km-1 and γ=24 W-1 km-1. Analysis of coding and decoding words "a" and "w" was done. Considering the propagation (with γ=9 W-1 km-1) of a word "w", an error occurred in all modulations except for simultaneous PPM/PAM modulation, which is associated to the better autocorrelation characteristics obtained with the OOK, PAM and PPM modulations alone, and could double the transmission rate. The nonlinear effects directly affect the process of the autocorrelation codes due to interference from adjacent chip components of the code.

  2. CHANNEL EVOLUTION AND EROSION IN PAM-TREATED AND UNTREATED EXPERIMENTAL WATERWAYS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Unprotected earthen waterways (e.g. grassed waterway before vegetation) and ephemeral gullies are prone to severe erosion. Previous research has suggested that polyacrylamide (PAM) may reduce erosion in areas of concentrated flow. This research tested the hypothesis that a PAM-treated channel would ...

  3. 40 CFR 52.2426 - Photochemical Assessment Monitoring Stations (PAMS) Program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) Virginia § 52.2426 Photochemical Assessment Monitoring Stations (PAMS) Program. On November 23, 1994 Virginia's... Stations (PAMS) Program on September 11, 1995 and made it part of the Virginia SIP. As with all...

  4. 40 CFR 52.2426 - Photochemical Assessment Monitoring Stations (PAMS) Program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) Virginia § 52.2426 Photochemical Assessment Monitoring Stations (PAMS) Program. On November 23, 1994 Virginia's... Stations (PAMS) Program on September 11, 1995 and made it part of the Virginia SIP. As with all...

  5. 40 CFR 52.2426 - Photochemical Assessment Monitoring Stations (PAMS) Program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) Virginia § 52.2426 Photochemical Assessment Monitoring Stations (PAMS) Program. On November 23, 1994 Virginia's... Stations (PAMS) Program on September 11, 1995 and made it part of the Virginia SIP. As with all...

  6. 40 CFR 52.2426 - Photochemical Assessment Monitoring Stations (PAMS) Program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) Virginia § 52.2426 Photochemical Assessment Monitoring Stations (PAMS) Program. On November 23, 1994 Virginia's... Stations (PAMS) Program on September 11, 1995 and made it part of the Virginia SIP. As with all...

  7. 40 CFR 52.2426 - Photochemical Assessment Monitoring Stations (PAMS) Program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) Virginia § 52.2426 Photochemical Assessment Monitoring Stations (PAMS) Program. On November 23, 1994 Virginia's... Stations (PAMS) Program on September 11, 1995 and made it part of the Virginia SIP. As with all...

  8. PHBV/PAM Scaffolds with Local Oriented Structure through UV Polymerization for Tissue Engineering

    PubMed Central

    Wang, Yingjun

    2014-01-01

    Locally oriented tissue engineering scaffolds can provoke cellular orientation and direct cell spread and migration, offering an exciting potential way for the regeneration of the complex tissue. Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) scaffolds with locally oriented hydrophilic polyacrylamide (PAM) inside the macropores of the scaffolds were achieved through UV graft polymerization. The interpenetrating PAM chains enabled good interconnectivity of PHBV/PAM scaffolds that presented a lower porosity and minor diameter of pores than PHBV scaffolds. The pores with diameter below 100 μm increased to 82.15% of PHBV/PAM scaffolds compared with 31.5% of PHBV scaffolds. PHBV/PAM scaffold showed a much higher compressive elastic modulus than PHBV scaffold due to PAM stuffing. At 5 days of culturing, sheep chondrocytes spread along the similar direction in the macropores of PHBV/PAM scaffolds. The locally oriented PAM chains might guide the attachment and spreading of chondrocytes and direct the formation of microfilaments via contact guidance. PMID:24579074

  9. 40 CFR 52.430 - Photochemical Assessment Monitoring Stations (PAMS) Program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Photochemical Assessment Monitoring Stations (PAMS) Program as a state implementation plan (SIP) revision, as... Stations (PAMS) Program on September 11, 1995 and made it part of the Delaware SIP. As with all components of the SIP, Delaware must implement the program as submitted and approved by EPA....

  10. Infiltration and Erosion in Soils Treated with Dry PAM of Two Molecular Weights and Phosphogypsum

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Soil surface application of dissolved linear polyacrylamide (PAM) of high molecular weight (MW) can mitigate seal formation, runoff and erosion, especially when added with a source of electrolytes (e.g., gypsum). Practical difficulties associated with PAM solution application prohibited commercial u...

  11. CHANNEL EVOLUTION AND EROSION IN PAM-TREATED AND UNTREATED EXPERIMENTAL WATERWAYS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Unprotected earthen waterways (e.g., grassed waterways before vegetation) and ephemeral gullies are prone to severe erosion. Previous research has suggested that polyacrylamide (PAM) may reduce erosion in areas of concentrated flow. This research tested the hypothesis that a PAM-treated channel woul...

  12. 40 CFR 52.2035 - Photochemical Assessment Monitoring Stations (PAMS) Program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...) Pennsylvania § 52.2035 Photochemical Assessment Monitoring Stations (PAMS) Program. On September 23, 1994... Clean Air Act. EPA approved the Photochemical Assessment Monitoring Stations (PAMS) Program on September 11, 1995 and made it part of Pennsylvania SIP. As with all components of the SIP, Pennsylvania...

  13. 40 CFR 52.2035 - Photochemical Assessment Monitoring Stations (PAMS) Program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...) Pennsylvania § 52.2035 Photochemical Assessment Monitoring Stations (PAMS) Program. On September 23, 1994... Clean Air Act. EPA approved the Photochemical Assessment Monitoring Stations (PAMS) Program on September 11, 1995 and made it part of Pennsylvania SIP. As with all components of the SIP, Pennsylvania...

  14. Generation 3 programmable array microscope (PAM) for high speed large format optical sectioning in fluorescence

    NASA Astrophysics Data System (ADS)

    de Vries, Anthony H. B.; Cook, Nathan P.; Kramer, Stephan; Arndt-Jovin, Donna J.; Jovin, Thomas M.

    2015-03-01

    We report on the current version of the optical sectioning programmable array microscope (PAM) implemented with a single digital micro-mirror device (DMD) spatial light modulator utilized as a mask in both the fluorescence excitation and emission paths. The PAM incorporates structured illumination and structured detection operating in synchrony. A sequence of binary patterns of excitation light in high definition format (1920×1080 elements) is projected into the focal plane of the microscope at the 18 kHz binary frame rate of the Texas Instruments 1080p DMD. The resulting fluorescent emission is captured as two distinct signals: conjugate (c, ca. "on-focus") consisting of light impinging on and deviated from the "on" elements of the DMD, and the non-conjugate (nc, ca. "out-of-focus") light falling on and deviated from the "off" elements. The two distinct, deflected beams are optically filtered and detected either by two individual cameras or captured as adjacent images on a single camera after traversing an image combiner. The sectioned image is gained from a subtraction of the nc image from the c image, weighted in accordance with the pattern(s) used for illumination and detection and the relative exposure times of the cameras. The widefield image is given by the sum of the c and nc images. This procedure allows a high duty cycle (typically 25-50%) of on-elements in the excitation patterns and thus functions with low light intensities, preventing saturation and minimizing photobleaching of sensitive fluorophores. The corresponding acquisition speed is also very high, limited only by the bandwidth of the camera(s) (100 fps full frame with the sCMOS camera in current use) and the optical power of the light source (lasers, large area LEDs). In contrast to the static patterns typical of SIM systems, the programmable array allows optimization of the patterns (duty cycle, feature size and distribution), thus enabling a wide range of applications, ranging from patterned

  15. Anionic Polyacrylamide (PAM) and Extracellular Polysaccharides (EPS) effects on flocculation and aggregate stability of soil

    NASA Astrophysics Data System (ADS)

    Albalasmeh, A. A.; Gharaibeh, M. A.; Ghezzehei, T. A.

    2015-12-01

    Soil structure influences many soil properties including aeration, water retention, drainage, bulk density, and resistance to erosion and indirectly influences most biological and chemical processes that occur in and around soil. A significant amount of literature showed that PAM plays an important role to control erosion. However, researchers are looking for more natural alternative for PAM. This study evaluated two anionic polymers including low and high molecular weight (MW), root exudates and bacterial exudates. We evaluated their influence on the rate and efficacy of colloid flocculation and the percent of water stable aggregates. We found that PAM was more effective than EPS in flocculating the colloids and all polymers increased the percent of stable soil aggregates although the PAM was more effective. These data suggest that the EPS would be less effective than PAM for reducing water erosion owing to its lesser flocculation and aggregate stabilizing potential.

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

    PubMed

    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/. PMID:22099701

  17. Preferential Acquisition and Activation of Plasminogen Glycoform II by PAM Positive Group A Streptococcal Isolates.

    PubMed

    De Oliveira, David M P; Law, Ruby H P; Ly, Diane; Cook, Simon M; Quek, Adam J; McArthur, Jason D; Whisstock, James C; Sanderson-Smith, Martina L

    2015-06-30

    Plasminogen (Plg) circulates in the host as two predominant glycoforms. Glycoform I Plg (GI-Plg) contains glycosylation sites at Asn289 and Thr346, whereas glycoform II Plg (GII-Plg) is exclusively glycosylated at Thr346. Surface plasmon resonance experiments demonstrated that Plg binding group A streptococcal M protein (PAM) exhibits comparative equal affinity for GI- and GII-Plg in the "closed" conformation (for GII-Plg, KD = 27.4 nM; for GI-Plg, KD = 37.0 nM). When Plg was in the "open" conformation, PAM exhibited an 11-fold increase in affinity for GII-Plg (KD = 2.8 nM) compared with that for GI-Plg (KD = 33.2 nM). The interaction of PAM with Plg is believed to be mediated by lysine binding sites within kringle (KR) 2 of Plg. PAM-GI-Plg interactions were fully inhibited with 100 mM lysine analogue ε-aminocaproic acid (εACA), whereas PAM-GII-Plg interactions were shown to be weakened but not inhibited in the presence of 400 mM εACA. In contrast, binding to the KR1-3 domains of GII-Plg (angiostatin) by PAM was completely inhibited in the presence 5 mM εACA. Along with PAM, emm pattern D GAS isolates express a phenotypically distinct SK variant (type 2b SK) that requires Plg ligands such as PAM to activate Plg. Type 2b SK was able to generate an active site and activate GII-Plg at a rate significantly higher than that of GI-Plg when bound to PAM. Taken together, these data suggest that GAS selectively recruits and activates GII-Plg. Furthermore, we propose that the interaction between PAM and Plg may be partially mediated by a secondary binding site outside of KR2, affected by glycosylation at Asn289. PMID:26029848

  18. Pam2 lipopeptides systemically increase myeloid-derived suppressor cells through TLR2 signaling

    SciTech Connect

    Maruyama, Akira; Shime, Hiroaki Takeda, Yohei; Azuma, Masahiro; Matsumoto, Misako; Seya, Tsukasa

    2015-02-13

    Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells that exhibit potent immunosuppressive activity. They are increased in tumor-bearing hosts and contribute to tumor development. Toll-like receptors (TLRs) on MDSCs may modulate the tumor-supporting properties of MDSCs through pattern-recognition. Pam2 lipopeptides represented by Pam2CSK4 serve as a TLR2 agonist to exert anti-tumor function by dendritic cell (DC)-priming that leads to NK cell activation and cytotoxic T cell proliferation. On the other hand, TLR2 enhances tumor cell progression/invasion by activating tumor-infiltrating macrophages. How MDSCs respond to TLR2 agonists has not yet been determined. In this study, we found intravenous administration of Pam2CSK4 systemically up-regulated the frequency of MDSCs in EG7 tumor-bearing mice. The frequency of tumor-infiltrating MDSCs was accordingly increased in response to Pam2CSK4. MDSCs were not increased by Pam2CSK4 stimuli in TLR2 knockout (KO) mice. Adoptive transfer experiments using CFSE-labeled MDSCs revealed that the TLR2-positive MDSCs survived long in tumor-bearing mice in response to Pam2CSK4 treatment. Since the increased MDSC population sustained immune-suppressive properties, our study suggests that Pam2CSK4-triggered TLR2 activation enhances the MDSC potential and suppress antitumor immune response in tumor microenvironment. - Highlights: • Pam2CSK4 administration induces systemic accumulation of CD11b{sup +}Gr1{sup +} MDSCs. • TLR2 is essential for Pam2CSK4-induced accumulation of CD11b{sup +}Gr1{sup +} MDSCs. • Pam2CSK4 supports survival of CD11b{sup +}Gr1{sup +} MDSCs in vivo.

  19. Psychometric Properties of the Hebrew Translation of the Patient Activation Measure (PAM-13)

    PubMed Central

    Magnezi, Racheli; Glasser, Saralee

    2014-01-01

    Objective “Patient activation” reflects involvement in managing ones health. This cross-sectional study assessed the psychometric properties of the Hebrew translation (PAM-H) of the PAM-13. Methods A nationally representative sample of 203 Hebrew-speaking Israeli adults answered the PAM-H, PHQ-9 depression scale, SF-12, and Self-efficacy Scale via telephone. Results Mean PAM-H scores were 70.7±15.4. Rasch analysis indicated that the PAM-H is a good measure of activation. There were no differences in PAM-H scores based on gender, age or education. Subjects with chronic disease scored lower than those without. Scores correlated with the Self-efficacy Scale (0.47), Total SF-12 (0.39) and PHQ-9 (−0.35, P<0.0001), indicating concurrent validity. Discriminant validity was reflected by a significant difference in the mean PAM-H score of those who scored below 10 (72.1±14.8) on the PHQ-9 (not depressed) compared to those scoring ≥10 (i.e. probable depression) (59.2±15.8; t 3.75; P = 0.001). Conclusion The PAM-H psychometric properties indicate its usefulness with the Hebrew-speaking Israeli population. Practice Implications PAM-H can be useful for assessing programs aimed at effecting changes in patient compliance, health behaviors, etc. Researchers in Israel should use a single translation of the PAM-13 so that findings can be compared, increasing understanding of patient activation. PMID:25411841

  20. Novel glycolipid TLR2 ligands of the type Pam2Cys-α-Gal: synthesis and biological properties.

    PubMed

    Thomann, Jean-Sébastien; Monneaux, Fanny; Creusat, Gaëlle; Spanedda, Maria Vittoria; Heurtault, Béatrice; Habermacher, Chloé; Schuber, Francis; Bourel-Bonnet, Line; Frisch, Benoît

    2012-05-01

    A more complete understanding of the mechanism of action of TLR agonists has fueled the investigation of new synthetic immunoadjuvants. In this context, we designed and synthesized glycolipids of the type Pam(2)Cys-α-Galactose as novel immunoadjuvants. Their synthesis required modifying a hydrophobic tBoc-[2,3-bispalmitoyloxy-(2R)-propyl]-R-cysteinyl moiety, i.e. the minimal structure required for TLR2 agonist activity, by addition of a hydrophilic head, either an α-Galactosylpyranose or an α-Galactosylfuranose to gain respectively Pam(2)CGalp and Pam(2)CGalf. While preparing a carbohydrate building block, an unexpected stereoselectivity was observed during a halide ion-catalytic process on a protected galactofuranose: the alpha anomer was obtained with surprisingly high selectivity (α/β ratio>9) and with good isolated yield (51%). The TLR2 binding properties of Pam(2)CGalp and Pam(2)CGalf were then fully evaluated. Their efficiency in triggering the proliferation of BALB/c mouse splenocytes was also compared to that of Pam(2)CAG and Pam(3)CAG, two well-established ligands of TLRs. Moreover, the maturation state of murine dendritic cells previously incubated with either Pam(2)CGalp or Pam(2)CGalf was monitored by flow cytometry and compared to that induced by lipopolysaccharide. Pam(2)CGalp and Pam(2)CGalf were found to be equivalent TLR2 agonists, and induced splenocyte proliferation and DC maturation. With very similar activity, Pam(2)CGalp and Pam(2)CGalf were also 10-fold to 100-fold better than Pam(2)CAG and Pam(3)CAG at inducing B cell proliferation. This represents the first time a glucidic head has been added to the tBoc-[2,3-bispalmitoyloxy-(2R)-propyl]-R-cysteinyl moiety whilst maintaining the immunomodulating activity. This should greatly enrich the data available on Pam(2)C structure/activity relationships. PMID:22483966

  1. Exploring with PAM: Prospecting ANTS Missions for Solar System Surveys

    NASA Technical Reports Server (NTRS)

    Clark, P. E.; Rilee, M. L.; Curtis, S. A.

    2003-01-01

    ANTS (Autonomous Nano-Technology Swarm), a large (1000 member) swarm of nano to picoclass (10 to 1 kg) totally autonomous spacecraft, are being developed as a NASA advanced mission concept. ANTS, based on a hierarchical insect social order, use an evolvable, self-similar, hierarchical neural system in which individual spacecraft represent the highest level nodes. ANTS uses swarm intelligence attained through collective, cooperative interactions of the nodes at all levels of the system. At the highest levels this can take the form of cooperative, collective behavior among the individual spacecraft in a very large constellation. The ANTS neural architecture is designed for totally autonomous operation of complex systems including spacecraft constellations. The ANTS (Autonomous Nano Technology Swarm) concept has a number of possible applications. A version of ANTS designed for surveying and determining the resource potential of the asteroid belt, called PAM (Prospecting ANTS Mission), is examined here.

  2. ANTS/PAM: Future Exploration of the Asteroid Belt

    NASA Astrophysics Data System (ADS)

    Clark, P. E.; Curtis, S. A.; Rilee, M. L.; Cheung, C. Y.

    2004-05-01

    The Autonomous Nano-Technology Swarm (ANTS) is applied to the Prospecting Asteroid Mission (PAM) concept, as part of a NASA RASC study. The ANTS architecture is inspired by success of social insect colonies, based on the division of labor within the colonies: 1) within their specialties, individual specialists generally outperform general-ists, and 2) with sufficiently efficient social interaction and coordination, the group of specialists generally outper-forms the group of generalists. ANTS as applied to PAM involves a thousand individual specialist `sciencecraft', one subswarm per target, in an environment where detection and tracking of irregular, infrequent targets is a major chal-lenge. Workers, carry and operate eight to nine different scientific instruments, including spectrometers, ranging and radio science devices, imagers. The remaining specialists, Messenger/Rulers, provide communication and coordina-tion. The non-expendable propulsion system is based on autonomously deployable and configurable solar sails, a system suitable to a low gravity environment. The design of the neural basis function requires a minimum of 4 or 5 specialists for collective decision making. Allowing for ten instrument specialist teams and compensating for antici-pated high attrition, we calculate an initial minimum of 100 per subswarm should allow characterization of hundreds of asteroids. The difficulty in observing irregular, rapidly moving, poorly illuminated objects is largely overcome by the ANT sciencecraft capability to optimize conditions for each instrument. Components are composed of carbon nanotubules reversibly deployable from NEMS nodes, allowing 100 times decrease in packaging volume. 1000 smart 10 centimeter, 1 kg cubic boxes create a 1000 kg 1 meter cube.

  3. Plasma Arc Melting (PAM) and Corrosion Resistance of Pure NiTi Shape Memory Alloys

    NASA Astrophysics Data System (ADS)

    Tuissi, A.; Rondelli, G.; Bassani, P.

    2015-03-01

    Plasma arc melting (PAM) as a suitable non-contaminating melting route for manufacturing high-quality NiTi alloy was successfully examined. The corrosion resistance of PAM Nitinol was evaluated by both potentiodynamic and potentiostatic tests and compared with lower purity NiTi produced by vacuum induction melting (VIM). For the electro-polished surfaces, excellent corrosion resistance of NiTi comparable with the Ti alloys was found with no pitting up to 800 mV versus saturated calomel electrode in simulated body fluid at 37 °C. Potentiostatic results of PAM Nitinol indicate slightly better corrosion resistance than the lower quality VIM alloy.

  4. In vivo analysis of Caenorhabditis elegans noncoding RNA promoter motifs

    PubMed Central

    Li, Tiantian; He, Housheng; Wang, Yunfei; Zheng, Haixia; Skogerbø, Geir; Chen, Runsheng

    2008-01-01

    Background Noncoding RNAs (ncRNAs) play important roles in a variety of cellular processes. Characterizing the transcriptional activity of ncRNA promoters is therefore a critical step toward understanding the complex cellular roles of ncRNAs. Results Here we present an in vivo transcriptional analysis of three C. elegans ncRNA upstream motifs (UM1-3). Transcriptional activity of all three motifs has been demonstrated, and mutational analysis revealed differential contributions of different parts of each motif. We showed that upstream motif 1 (UM1) can drive the expression of green fluorescent protein (GFP), and utilized this for detailed analysis of temporal and spatial expression patterns of 5 SL2 RNAs. Upstream motifs 2 and 3 do not drive GFP expression, and termination at consecutive T runs suggests transcription by RNA polymerase III. The UM2 sequence resembles the tRNA promoter, and is actually embedded within its own short-lived, primary transcript. This is a structure which is also found at a few plant and yeast loci, and may indicate an evolutionarily very old dicistronic transcription pattern in which a tRNA serves as a promoter for an adjacent snoRNA. Conclusion The study has demonstrated that the three upstream motifs UM1-3 have promoter activity. The UM1 sequence can drive expression of GFP, which allows for the use of UM1::GFP fusion constructs to study temporal-spatial expression patterns of UM1 ncRNA loci. The UM1 loci appear to act in concert with other upstream sequences, whereas the transcriptional activities of the UM2 and UM3 are confined to the motifs themselves. PMID:18680611

  5. 40 CFR 52.2035 - Photochemical Assessment Monitoring Stations (PAMS) Program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... (PAMS) Program as a state implementation plan (SIP) revision, as required by section 182(c)(1) of the... 11, 1995 and made it part of Pennsylvania SIP. As with all components of the SIP, Pennsylvania...

  6. Effects of miso- and mesoscale obstructions on PAM winds obtained during project NIMROD. [Portable Automated Mesonet

    NASA Technical Reports Server (NTRS)

    Fujita, T. T.; Wakimoto, R. M.

    1982-01-01

    Data from 27 PAM (Portable Automated Mesonet) stations, operational as a phase of project NIMROD (Northern Illinois Meteorological Research on Downburst), are presented. It was found that PAM-measured winds are influenced by the mesoscale obstruction of the Chicago metropolitan area, as well as by the misoscale obstruction of identified trees and buildings. The mesoscale obstruction was estimated within the range of near zero to 50%, increasing toward the city limits, while the misoscale obstruction was estimated as being as large as 58% near obstructing trees which were empirically calculated to cause a wind speed deficit 50-80 times their height. Despite a statistical analysis based on one-million PAM winds, wind speed and stability transmission factors could not be accurately calculated; thus, in order to calculate the airflow free from obstacle, PAM-measured winds must be corrected.

  7. Preparation and characterization of BC/PAM-AgNPs nanocomposites for antibacterial applications.

    PubMed

    Yang, Guang; Wang, Caixia; Hong, Feng; Yang, Xuexia; Cao, Zhangjun

    2015-01-22

    In this work, a bacterial cellulose/polyacrylamide (BC/PAM) double network composite was prepared to act as the template for in situ synthesis of silver nanoparticles (AgNPs). Effects of reaction conditions of the BC/PAM composite were investigated on its microstructure, mechanical properties and thermal stabilities. Both the BC/PAM composite and pure BC were utilized to prepare the corresponding silver impregnated nanocomposites, i.e., BC/PAM-AgNPs and BC-AgNPs, by an environmental friendly method, UV irradiation. The influences of the templates were investigated on the AgNPs formation and the antibacterial activities of the nanocomposites by both the zone of inhibition and dynamic shake flask methods. It was shown that the BC/PAM composite displayed a denser microstructure and higher thermal stabilities than pure BC. The BC/PAM-AgNPs nanocomposite exhibited a bigger particle size and lower mass content of AgNPs than the BC-AgNPs one. For the antibacterial test, two nanocomposites exhibited a close antibacterial effect, with a high log reduction above 3 and killing ratio above 99.9%, respectively. PMID:25439942

  8. The Annotation of RNA Motifs

    PubMed Central

    2002-01-01

    The recent deluge of new RNA structures, including complete atomic-resolution views of both subunits of the ribosome, has on the one hand literally overwhelmed our individual abilities to comprehend the diversity of RNA structure, and on the other hand presented us with new opportunities for comprehensive use of RNA sequences for comparative genetic, evolutionary and phylogenetic studies. Two concepts are key to understanding RNA structure: hierarchical organization of global structure and isostericity of local interactions. Global structure changes extremely slowly, as it relies on conserved long-range tertiary interactions. Tertiary RNA–RNA and quaternary RNA–protein interactions are mediated by RNA motifs, defined as recurrent and ordered arrays of non-Watson–Crick base-pairs. A single RNA motif comprises a family of sequences, all of which can fold into the same three-dimensional structure and can mediate the same interaction(s). The chemistry and geometry of base pairing constrain the evolution of motifs in such a way that random mutations that occur within motifs are accepted or rejected insofar as they can mediate a similar ordered array of interactions. The steps involved in the analysis and annotation of RNA motifs in 3D structures are: (a) decomposition of each motif into non-Watson–Crick base-pairs; (b) geometric classification of each basepair; (c) identification of isosteric substitutions for each basepair by comparison to isostericity matrices; (d) alignment of homologous sequences using the isostericity matrices to identify corresponding positions in the crystal structure; (e) acceptance or rejection of the null hypothesis that the motif is conserved. PMID:18629252

  9. Redox active motifs in selenoproteins.

    PubMed

    Li, Fei; Lutz, Patricia B; Pepelyayeva, Yuliya; Arnér, Elias S J; Bayse, Craig A; Rozovsky, Sharon

    2014-05-13

    Selenoproteins use the rare amino acid selenocysteine (Sec) to act as the first line of defense against oxidants, which are linked to aging, cancer, and neurodegenerative diseases. Many selenoproteins are oxidoreductases in which the reactive Sec is connected to a neighboring Cys and able to form a ring. These Sec-containing redox motifs govern much of the reactivity of selenoproteins. To study their fundamental properties, we have used (77)Se NMR spectroscopy in concert with theoretical calculations to determine the conformational preferences and mobility of representative motifs. This use of (77)Se as a probe enables the direct recording of the properties of Sec as its environment is systematically changed. We find that all motifs have several ring conformations in their oxidized state. These ring structures are most likely stabilized by weak, nonbonding interactions between the selenium and the amide carbon. To examine how the presence of selenium and ring geometric strain governs the motifs' reactivity, we measured the redox potentials of Sec-containing motifs and their corresponding Cys-only variants. The comparisons reveal that for C-terminal motifs the redox potentials increased between 20-25 mV when the selenenylsulfide bond was changed to a disulfide bond. Changes of similar magnitude arose when we varied ring size or the motifs' flanking residues. This suggests that the presence of Sec is not tied to unusually low redox potentials. The unique roles of selenoproteins in human health and their chemical reactivities may therefore not necessarily be explained by lower redox potentials, as has often been claimed. PMID:24769567

  10. [Prediction of Promoter Motifs in Virophages].

    PubMed

    Gong, Chaowen; Zhou, Xuewen; Pan, Yingjie; Wang, Yongjie

    2015-07-01

    Virophages have crucial roles in ecosystems and are the transport vectors of genetic materials. To shed light on regulation and control mechanisms in virophage--host systems as well as evolution between virophages and their hosts, the promoter motifs of virophages were predicted on the upstream regions of start codons using an analytical tool for prediction of promoter motifs: Multiple EM for Motif Elicitation. Seventeen potential promoter motifs were identified based on the E-value, location, number and length of promoters in genomes. Sputnik and zamilon motif 2 with AT-rich regions were distributed widely on genomes, suggesting that these motifs may be associated with regulation of the expression of various genes. Motifs containing the TCTA box were predicted to be late promoter motif in mavirus; motifs containing the ATCT box were the potential late promoter motif in the Ace Lake mavirus . AT-rich regions were identified on motif 2 in the Organic Lake virophage, motif 3 in Yellowstone Lake virophage (YSLV)1 and 2, motif 1 in YSLV3, and motif 1 and 2 in YSLV4, respectively. AT-rich regions were distributed widely on the genomes of virophages. All of these motifs may be promoter motifs of virophages. Our results provide insights into further exploration of temporal expression of genes in virophages as well as associations between virophages and giant viruses. PMID:26524912

  11. Seepage from channeled flows as influenced by PAM and sediment

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Seepage from water streams into unlined channels determines the proportion of water distributed to adjacent soil for plant use or soil or groundwater recharge, or conveyed to downstream reaches. We conducted a laboratory study to determine how sediment type (none, clay, silt), sediment concentratio...

  12. Specific RNA self-assembly with minimal paranemic motifs

    PubMed Central

    Afonin, Kirill A.; Cieply, Dennis J.; Leontis, Neocles B.

    2016-01-01

    The paranemic crossover (PX) is a motif for assembling two nucleic acid molecules using Watson-Crick (WC) basepairing without unfolding pre-formed secondary structure in the individual molecules. Once formed, the paranemic assembly motif comprises adjacent parallel double helices that cross over at every possible point over the length of the motif. The interaction is reversible as it does not require denaturation of basepairs internal to each interacting molecular unit. Paranemic assembly has been demonstrated for DNA but not for RNA, and only for motifs with four or more cross-over points and lengths of five or more helical half-turns. Here we report the design of RNA molecules that paranemically assemble with the minimum number of two cross-overs spanning the major groove to form paranemic motifs with a length of three half-turns (3HT). Dissociation constants (Kds) were measured for series of molecules in which the number of basepairs between the cross-over points was varied from five to eight basepairs. The paranemic 3HT complex with six basepairs (3HT_6M) was found to be the most stable with Kd = 1×10−8 M. The half-time for kinetic exchange of the 3HT_6M complex was determined to be ~100 minutes, from which we calculated association and dissociation rate constants ka = 5.11×103 M−1sec−1 and kd = 5.11×10−5 sec−1. RNA paranemic assembly of 3HT and 5HT complexes is blocked by single-base substitutions that disrupt individual inter-molecular Watson-Crick basepairs and is restored by compensatory substitutions that restore those basepairs. The 3HT motif appears suitable for specific, programmable, and reversible tecto-RNA self-assembly for constructing artificial RNA molecular machines. PMID:18072767

  13. Sequential visibility-graph motifs

    NASA Astrophysics Data System (ADS)

    Iacovacci, Jacopo; Lacasa, Lucas

    2016-04-01

    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 sequential visibility-graph motifs, smaller substructures of n consecutive nodes that appear with characteristic frequencies. We develop a theory to compute in an exact way the motif profiles associated with general classes of deterministic and stochastic dynamics. We find that this simple property is indeed a highly informative and computationally efficient feature capable of distinguishing 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 and description of physical, biological, and financial time series.

  14. Comparison of 2-PAM and pro-2-PAM containing treatment regimens as antagonists of nerve agent-induced lethality and incapacitation. Final report, June 1981-December 1985

    SciTech Connect

    Talbot, B.G.; Harris, L.W.; Lennox, W.J.; Anderson, D.A.; Green, M.D.

    1986-09-01

    In vivo, (2-Puridine Aldoxine Methioidide) reactivates phosphonylated acetylcholinesterase AChE peripherally, but is effective in restoring AChE centrally because the quaternary nitrogen atom of 2-PAM prevents penetration of the brain. The problem was solved by the synthesis of the 1,6-dihyropyridine derivative of 2-PAM, pro-2-PAM (PP). Functional brain AChE is related to return to control performance on an accelerating rotarod (ARR) in animals intoxicated with soman. There should be a difference in the time to recovery of control ARR performance between PP- and 2-PAM-treated, sarin-intoxicated animals. In the present work, an ARR decrement free dosage (DFD) of each of these oximes (30 mg/kg, im) in combination with DFD of atropine (A) and mecamylamine (M) (0.79 mg/kg each, im) was used as pretreatment against sarin-induced deficit. The same antidotes were given pre-and post- intoxication (as pretreatment and therapy) to anatagonize sarin-induced lethality; the PP containing antidote provided significantly greater protection than that by the 2-PAM antidote which in turn provided significant protection over control. Neither antidote when given as pretreatment and therapy provided protection above control against soman-induced physical incapacitation, but they were equally effective in antagonizing VX-induced physical incapacitation. The reversal of sarin-induced physical debilitation reflects the central actions of PP and supports the notion that functional brain AChE activity is essential for rapid recovery from the debilitating effeclts on nerve agents.

  15. Effective PCR-based detection of Naegleria fowleri from cultured sample and PAM-developed mouse.

    PubMed

    Kang, Heekyoung; Seong, Gi-Sang; Sohn, Hae-Jin; Kim, Jong-Hyun; Lee, Sang-Eun; Park, Mi Yeoun; Lee, Won-Ja; Shin, Ho-Joon

    2015-10-01

    Increasing numbers of Primary Amoebic Meningoencephalitis (PAM) cases due to Naegleria fowleri are becoming a serious issue in subtropical and tropical countries as a Neglected Tropical Disease (NTD). To establish a rapid and effective diagnostic tool, a PCR-based detection technique was developed based on previous PCR methods. Four kinds of primer pairs, Nfa1, Nae3, Nf-ITS, and Naegl, were employed in the cultured amoebic trophozoites and a mouse with PAM experimentally developed by N. fowleri inoculation (PAM-mouse). For the extraction of genomic DNA from N. fowleri trophozoites (1×10(6)), simple boiling with 10μl of PBS (pH 7.4) at 100°C for 30min was found to be the most rapid and efficient procedure, allowing amplification of 2.5×10(2) trophozoites using the Nfa-1 primer. The primers Nfa1 and Nae3 amplified only N. fowleri DNA, whereas the ITS primer detected N. fowleri and N. gruberi DNA. Using the PAM-mouse brain tissue, the Nfa1 primer was able to amplify the N. fowleri DNA 4 days post infection with 1ng/μl of genomic DNA being detectable. Using the PAM-mouse CSF, amplification of the N. fowleri DNA with the Nae3 primer was possible 5 days post infection showing a better performance than the Nfa1 primer at day 6. PMID:26322498

  16. Feasibility investigation of oily wastewater treatment by combination of zinc and PAM in coagulation/flocculation.

    PubMed

    Zeng, Yubin; Yang, Changzhu; Zhang, Jingdong; Pu, Wenhong

    2007-08-25

    Poly-zinc silicate (PZSS) is a new type of coagulant with cationic polymer synthesized by polysilicic acid and zinc sulfate. It has been used in several sorts of wastewaters treatment, but not used in oily wastewater treatment. In this study, we investigated the coagulation/flocculation of oil and suspended solids in heavy oil wastewater (HOW) by PZSS and anion polyacrylamide (A-PAM). The properties of PZSS cooperated with A-PAM were compared with PAC and PFS in dosages, PAMs amount, settling time, pH value and flocs morphology. The results showed that PZSS was more efficient than PAC and PFS. Under the optimum experimental conditions of coagulation/flocculation (dosage: 100mg/L, A-PAM dosage: 1.0mg/L, settling time time: 40min and pH 6.5-9.5), more than 99% of oil was removed and suspended solid value less than 5mg/L by using PZSS cooperated with A-PAM, which could satisfy the demands of the pre-treatment process for HOW to be reused in the steam boiler or recycled into the injecting well. PMID:17350754

  17. Redox active motifs in selenoproteins

    PubMed Central

    Li, Fei; Lutz, Patricia B.; Pepelyayeva, Yuliya; Arnér, Elias S. J.; Bayse, Craig A.; Rozovsky, Sharon

    2014-01-01

    Selenoproteins use the rare amino acid selenocysteine (Sec) to act as the first line of defense against oxidants, which are linked to aging, cancer, and neurodegenerative diseases. Many selenoproteins are oxidoreductases in which the reactive Sec is connected to a neighboring Cys and able to form a ring. These Sec-containing redox motifs govern much of the reactivity of selenoproteins. To study their fundamental properties, we have used 77Se NMR spectroscopy in concert with theoretical calculations to determine the conformational preferences and mobility of representative motifs. This use of 77Se as a probe enables the direct recording of the properties of Sec as its environment is systematically changed. We find that all motifs have several ring conformations in their oxidized state. These ring structures are most likely stabilized by weak, nonbonding interactions between the selenium and the amide carbon. To examine how the presence of selenium and ring geometric strain governs the motifs’ reactivity, we measured the redox potentials of Sec-containing motifs and their corresponding Cys-only variants. The comparisons reveal that for C-terminal motifs the redox potentials increased between 20–25 mV when the selenenylsulfide bond was changed to a disulfide bond. Changes of similar magnitude arose when we varied ring size or the motifs’ flanking residues. This suggests that the presence of Sec is not tied to unusually low redox potentials. The unique roles of selenoproteins in human health and their chemical reactivities may therefore not necessarily be explained by lower redox potentials, as has often been claimed. PMID:24769567

  18. Electrochemical examination of ability of dsDNA/PAM composites for storing and releasing of doxorubicin.

    PubMed

    Zabost, Ewelina; Liwinska, Wioletta; Karbarz, Marcin; Kurek, Eliza; Lyp, Marek; Donten, Mikolaj; Stojek, Zbigniew

    2016-06-01

    Composites consisting of ss- and ds-DNA strands and polyacrylamide (PAM) hydrogel have been synthesized. DNA was entrapped non-covalently. The obtained DNA biomaterial exhibited a strong increase in guanine and adenine anodic currents when temperature reached the physiological level. This increase was related to the unique oligonucleotide structural changes in the composite. The structural alterations in the PAM lattices were employed for the release of the drug accumulated in the composite. Doxorubicin (Dox) was selected as the drug; it was accumulated by intercalation to dsDNA and was slowly released from the dsDNA/PAM system by using a minor temperature increase (up to 40÷45°C) as it is routinely done in hyperthermia. The applied release temperature was either constant or oscillating. The binding strength, the rate of Dox release and the properties of the composite were examined using voltammetry, SEM and ICP-MS. PMID:26764570

  19. Control of Methicillin-Resistant Staphylococcus aureus Pneumonia Utilizing TLR2 Agonist Pam3CSK4.

    PubMed

    Chen, Yi-Guo; Zhang, Yong; Deng, Lin-Qiang; Chen, Hui; Zhang, Yu-Juan; Zhou, Nan-Jin; Yuan, Keng; Yu, Li-Zhi; Xiong, Zhang-Hua; Gui, Xiao-Mei; Yu, Yan-Rong; Wu, Xiao-Mu; Min, Wei-Ping

    2016-01-01

    The spread of methicillin-resistant Staphylococcus aureus (MRSA) is a critical health issue that has drawn greater attention to the potential use of immunotherapy. Toll-like receptor 2 (TLR2), a pattern recognition receptor, is an essential component in host innate defense system against S. aureus infection. However, little is known about the innate immune response, specifically TLR2 activation, against MRSA infection. Here, we evaluate the protective effect and the mechanism of MRSA murine pneumonia after pretreatment with Pam3CSK4, a TLR2 agonist. We found that the MRSA-pneumonia mouse model, pretreated with Pam3CSK4, had reduced bacteria and mortality in comparison to control mice. As well, lower protein and mRNA levels of TNF-α, IL-1β and IL-6 were observed in lungs and bronchus of the Pam3CSK4 pretreatment group. Conversely, expression of anti-inflammatory cytokine IL-10, but not TGF-β, increased in Pam3CSK4-pretreated mice. Our additional studies showed that CXCL-2 and CXCL1, which are necessary for neutrophil recruitment, were less evident in the Pam3CSK4-pretreated group compared to control group, whereas the expression of Fcγ receptors (FcγⅠ/Ⅲ) and complement receptors (CR1/3) increased in murine lungs. Furthermore, we found that increased survival and improved bacterial clearance were not a result of higher levels of neutrophil infiltration, but rather a result of enhanced phagocytosis and bactericidal activity of neutrophils in vitro and in vivo as well as increased robust oxidative activity and release of lactoferrin. Our cumulative findings suggest that Pam3CSK4 could be a novel immunotherapeutic candidate against MRSA pneumonia. PMID:26974438

  20. Control of Methicillin-Resistant Staphylococcus aureus Pneumonia Utilizing TLR2 Agonist Pam3CSK4

    PubMed Central

    Chen, Yi-Guo; Zhang, Yong; Deng, Lin-Qiang; Chen, Hui; Zhang, Yu-Juan; Zhou, Nan-Jin; Yuan, Keng; Yu, Li-Zhi; Xiong, Zhang-Hua; Gui, Xiao-Mei; Yu, Yan-Rong; Wu, Xiao-Mu; Min, Wei-Ping

    2016-01-01

    The spread of methicillin-resistant Staphylococcus aureus (MRSA) is a critical health issue that has drawn greater attention to the potential use of immunotherapy. Toll-like receptor 2 (TLR2), a pattern recognition receptor, is an essential component in host innate defense system against S. aureus infection. However, little is known about the innate immune response, specifically TLR2 activation, against MRSA infection. Here, we evaluate the protective effect and the mechanism of MRSA murine pneumonia after pretreatment with Pam3CSK4, a TLR2 agonist. We found that the MRSA-pneumonia mouse model, pretreated with Pam3CSK4, had reduced bacteria and mortality in comparison to control mice. As well, lower protein and mRNA levels of TNF-α, IL-1β and IL-6 were observed in lungs and bronchus of the Pam3CSK4 pretreatment group. Conversely, expression of anti-inflammatory cytokine IL-10, but not TGF-β, increased in Pam3CSK4-pretreated mice. Our additional studies showed that CXCL-2 and CXCL1, which are necessary for neutrophil recruitment, were less evident in the Pam3CSK4-pretreated group compared to control group, whereas the expression of Fcγ receptors (FcγⅠ/Ⅲ) and complement receptors (CR1/3) increased in murine lungs. Furthermore, we found that increased survival and improved bacterial clearance were not a result of higher levels of neutrophil infiltration, but rather a result of enhanced phagocytosis and bactericidal activity of neutrophils in vitro and in vivo as well as increased robust oxidative activity and release of lactoferrin. Our cumulative findings suggest that Pam3CSK4 could be a novel immunotherapeutic candidate against MRSA pneumonia. PMID:26974438

  1. The Thiamin Pyrophosphate-Motif

    NASA Technical Reports Server (NTRS)

    Dominiak, P.; Ciszak, E.

    2003-01-01

    Using databases the authors have identified a common thiamin pyrophosphate (TPP)-motif in the family of functionally diverse TPP-dependent enzymes. This common motif consists of multimeric organization of subunits and two catalytic centers. Each catalytic center (PP:PYR) is formed at the interface of the PP-domain binding the magnesium ion, pyrophosphate and amhopyrimidine ring of TPP, and the PYR-domain binding the aminopyrimidine ring of that cofactor. A pair of these catalytic centers constitutes the catalytic core (PP:PYR)(sub 2) within these enzymes. Analysis of the structural elements of this catalytic core reveals novel definition of the common amino acid sequences, which are GXPhiX(sub 4)(G)PhiXXGQ and GDGX(sub 25-30)NN in the PP-domain, and the EX(sub 4)(G)PhiXXGPhi in the PYR-domain, where Phi corresponds to a hydrophobic amino acid. This TPP-motif provides a novel tool for annotation of TPP-dependent enzymes useful in advancing functional proteomics.

  2. The Thiamin Pyrophosphate-Motif

    NASA Technical Reports Server (NTRS)

    Dominiak, Paulina M.; Ciszak, Ewa M.

    2003-01-01

    Using databases the authors have identified a common thiamin pyrophosphate (TPP)-motif in the family of functionally diverse TPP-dependent enzymes. This common motif consists of multimeric organization of subunits, two catalytic centers, common amino acid sequence, and specific contacts to provide a flip-flop, or alternate site, mechanism of action. Each catalytic center [PP:PYR] is formed at the interface of the PP-domain binding the magnesium ion, pyrophosphate and aminopyrimidine ring of TPP, and the PYR-domain binding the aminopyrimidine ring of that cofactor. A pair of these catalytic centers constitutes the catalytic core [PP:PYR]* within these enzymes. Analysis of the structural elements of this catalytic core reveals novel definition of the common amino acid sequences, which are GX@&(G)@XXGQ, and GDGX25-30 within the PP- domain, and the E&(G)@XXG@ within the PYR-domain, where Q, corresponds to a hydrophobic amino acid. This TPP-motif provides a novel tool for annotation of TPP-dependent enzymes useful in advancing functional proteomics.

  3. Comprehensive discovery of DNA motifs in 349 human cells and tissues reveals new features of motifs

    PubMed Central

    Zheng, Yiyu; Li, Xiaoman; Hu, Haiyan

    2015-01-01

    Comprehensive motif discovery under experimental conditions is critical for the global understanding of gene regulation. To generate a nearly complete list of human DNA motifs under given conditions, we employed a novel approach to de novo discover significant co-occurring DNA motifs in 349 human DNase I hypersensitive site datasets. We predicted 845 to 1325 motifs in each dataset, for a total of 2684 non-redundant motifs. These 2684 motifs contained 54.02 to 75.95% of the known motifs in seven large collections including TRANSFAC. In each dataset, we also discovered 43 663 to 2 013 288 motif modules, groups of motifs with their binding sites co-occurring in a significant number of short DNA regions. Compared with known interacting transcription factors in eight resources, the predicted motif modules on average included 84.23% of known interacting motifs. We further showed new features of the predicted motifs, such as motifs enriched in proximal regions rarely overlapped with motifs enriched in distal regions, motifs enriched in 5′ distal regions were often enriched in 3′ distal regions, etc. Finally, we observed that the 2684 predicted motifs classified the cell or tissue types of the datasets with an accuracy of 81.29%. The resources generated in this study are available at http://server.cs.ucf.edu/predrem/. PMID:25505144

  4. Dimerization Is Not a Determining Factor for Functional High Affinity Human Plasminogen Binding by the Group A Streptococcal Virulence Factor PAM and Is Mediated by Specific Residues within the PAM a1a2 Domain*

    PubMed Central

    Bhattacharya, Sarbani; Liang, Zhong; Quek, Adam J.; Ploplis, Victoria A.; Law, Ruby; Castellino, Francis J.

    2014-01-01

    A emm53 subclass of Group A Streptococcus pyogenes (GAS) interacts tightly with human plasma plasminogen (hPg) and plasmin (hPm) via the kringle 2 (K2hPg) domain of hPg/hPm and the N-terminal a1a2 regions of a GAS coiled-coil M-like protein (PAM). Previous studies have shown that a monomeric PAM fragment, VEK30 (residues 97–125 + Tyr), interacted specifically with isolated K2hPg. However, the binding strength of VEK30 (KD = 56 nm) was ∼60-fold weaker than that of full-length dimeric PAM (KD = 1 nm). To assess whether this attenuated binding was due to the inability of VEK30 to dimerize, we defined the minimal length of PAM required to dimerize using a series of peptides with additional PAM residues placed at the NH2 and COOH termini of VEK30. VEK64 (PAM residues 83–145 + Tyr) was found to be the smallest peptide that adopted an α-helical dimer, and was bound to K2hPg with nearly the same affinity as PAM (KD = 1–2 nm). However, addition of two PAM residues (Arg126-His127) to the COOH terminus of VEK30 (VEK32) maintained a monomeric peptidic structure, but exhibited similar K2hPg binding affinity as full-length dimeric PAM. We identified five residues in a1a2 (Arg113, His114, Glu116, Arg126, His127), mutation of which reduced PAM binding affinity for K2hPg by ∼1000-fold. Replacement of these critical residues by Ala in the GAS genome resulted in reduced virulence, similar to the effects of inactivating the PAM gene entirely. We conclude that rather than dimerization of PAM, the five key residues in the binding domain of PAM are essential to mediate the high affinity interaction with hPg, leading to increased GAS virulence. PMID:24962580

  5. Dimerization is not a determining factor for functional high affinity human plasminogen binding by the group A streptococcal virulence factor PAM and is mediated by specific residues within the PAM a1a2 domain.

    PubMed

    Bhattacharya, Sarbani; Liang, Zhong; Quek, Adam J; Ploplis, Victoria A; Law, Ruby; Castellino, Francis J

    2014-08-01

    A emm53 subclass of Group A Streptococcus pyogenes (GAS) interacts tightly with human plasma plasminogen (hPg) and plasmin (hPm) via the kringle 2 (K2hPg) domain of hPg/hPm and the N-terminal a1a2 regions of a GAS coiled-coil M-like protein (PAM). Previous studies have shown that a monomeric PAM fragment, VEK30 (residues 97-125 + Tyr), interacted specifically with isolated K2hPg. However, the binding strength of VEK30 (KD = 56 nm) was ∼60-fold weaker than that of full-length dimeric PAM (KD = 1 nm). To assess whether this attenuated binding was due to the inability of VEK30 to dimerize, we defined the minimal length of PAM required to dimerize using a series of peptides with additional PAM residues placed at the NH2 and COOH termini of VEK30. VEK64 (PAM residues 83-145 + Tyr) was found to be the smallest peptide that adopted an α-helical dimer, and was bound to K2hPg with nearly the same affinity as PAM (KD = 1-2 nm). However, addition of two PAM residues (Arg(126)-His(127)) to the COOH terminus of VEK30 (VEK32) maintained a monomeric peptidic structure, but exhibited similar K2hPg binding affinity as full-length dimeric PAM. We identified five residues in a1a2 (Arg(113), His(114), Glu(116), Arg(126), His(127)), mutation of which reduced PAM binding affinity for K2hPg by ∼ 1000-fold. Replacement of these critical residues by Ala in the GAS genome resulted in reduced virulence, similar to the effects of inactivating the PAM gene entirely. We conclude that rather than dimerization of PAM, the five key residues in the binding domain of PAM are essential to mediate the high affinity interaction with hPg, leading to increased GAS virulence. PMID:24962580

  6. Detecting correlations among functional-sequence motifs

    NASA Astrophysics Data System (ADS)

    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.

  7. Detecting correlations among functional-sequence motifs.

    PubMed

    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. PMID:23005179

  8. From the Field: Speech Therapy Outcome Measures--Interview with Dr. Pam Enderby

    ERIC Educational Resources Information Center

    Montgomery, Judy K.

    2015-01-01

    This article is an interview with Dr. Pam Enderby--a speech language therapist and professor at the Institute of General Practice and Primary Care at the University of Sheffield, Community Sciences Centre, Northern General Hospital, in the United Kingdom--conducted by Judy Montgomery, Editor in Chief, of "Communication Disorders…

  9. Evaluation of the blood level duration properties of procaine benzylpenicillin in oil with aluminium monostearate (PAM)*

    PubMed Central

    Bond, Jillian M.; Lightbown, J. W.; Mussett, Marjorie V.; Woodward, Patricia M.

    1965-01-01

    The study of procaine benzylpenicillin in oil with aluminium monostearate (PAM) described in this paper was undertaken to devise laboratory assay methods, based on animal tests, to evaluate those properties of PAM responsible for the persistence of penicillin in the circulation, as a preferable substitute for the existing test in man. Comparative studies of a number of batches of PAM in man proved, with statistical certainty, that the duration of the blood level of penicillin which they produced varied from batch to batch. The chemical and physical properties of the batches gave inadequate characterization and were of no value in assessing material for clinical use. A blood level duration test in rabbits was developed which reflected the blood level duration properties shown in man. The test was incorporated in the Requirements for Procaine Benzylpenicillin in Oil with Aluminium Monostearate that were set up by the WHO Expert Committee on Biological Standardization to ensure the suitability of batches for clinical use. An International Reference Preparation was necessary and was established. Batches of PAM in use in the field by WHO in anti-yaws campaigns were examined by the test described and found to be satisfactory. ImagesFIG. 5 PMID:5295406

  10. Runoff and interrill erosion in sodic soils treated with dry PAM and phosphogypsum

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Seal formation at the soil surface during rainstorms reduces rain infiltration and leads to runoff and erosion. An increase in soil sodicity increases soil susceptibility to crusting, runoff, and erosion. Surface application of dissolved polyacrylamide (PAM) mixed with gypsum was found to be very ef...

  11. Of Wondrous Places and "Benevolent Neglect": An Interview with Pam Munoz Ryan

    ERIC Educational Resources Information Center

    Fabbi, Jennifer; Johnson, Amy

    2007-01-01

    With her recent book, "Paint the Wind" (2007), hitting the shelves this fall, author Pam Munoz Ryan delivers a welcome addition to the 25 plus books she has written for young people, including her award-winning novels "Esperanza Rising" (2000) and "Riding Freedom" (1998) and picture books "Amelia and Eleanor Go for a Ride" (1999) and "When Marian…

  12. Solid-liquid separation of dairy manure with PAM and chitosan polymers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Organic polymers are useful to increase separation of suspended solids and carbon compounds from liquid swine manure, but experiences with dairy manure are limited. In this experiment, two polymers, a synthetic polyacrylamide (PAM) and a natural chitosan were used to increase separation of suspended...

  13. A survey of DNA motif finding algorithms

    PubMed Central

    Das, Modan K; Dai, Ho-Kwok

    2007-01-01

    Background Unraveling the mechanisms that regulate gene expression is a major challenge in biology. An important task in this challenge is to identify regulatory elements, especially the binding sites in deoxyribonucleic acid (DNA) for transcription factors. These binding sites are short DNA segments that are called motifs. Recent advances in genome sequence availability and in high-throughput gene expression analysis technologies have allowed for the development of computational methods for motif finding. As a result, a large number of motif finding algorithms have been implemented and applied to various motif models over the past decade. This survey reviews the latest developments in DNA motif finding algorithms. Results Earlier algorithms use promoter sequences of coregulated genes from single genome and search for statistically overrepresented motifs. Recent algorithms are designed to use phylogenetic footprinting or orthologous sequences and also an integrated approach where promoter sequences of coregulated genes and phylogenetic footprinting are used. All the algorithms studied have been reported to correctly detect the motifs that have been previously detected by laboratory experimental approaches, and some algorithms were able to find novel motifs. However, most of these motif finding algorithms have been shown to work successfully in yeast and other lower organisms, but perform significantly worse in higher organisms. Conclusion Despite considerable efforts to date, DNA motif finding remains a complex challenge for biologists and computer scientists. Researchers have taken many different approaches in developing motif discovery tools and the progress made in this area of research is very encouraging. Performance comparison of different motif finding tools and identification of the best tools have proven to be a difficult task because tools are designed based on algorithms and motif models that are diverse and complex and our incomplete understanding of

  14. A20 Is Critical for the Induction of Pam3CSK4-Tolerance in Monocytic THP-1 Cells

    PubMed Central

    Hu, Jinyue; Wang, Guihua; Liu, Xueting; Zhou, Lina; Jiang, Manli; Yang, Li

    2014-01-01

    A20 functions to terminate Toll-like receptor (TLR)-induced immune response, and play important roles in the induction of lipopolysacchride (LPS)-tolerance. However, the molecular mechanism for Pam3CSK4-tolerance is uncertain. Here we report that TLR1/2 ligand Pam3CSK4 induced tolerance in monocytic THP-1 cells. The pre-treatment of THP-1 cells with Pam3CSK4 down-regulated the induction of pro-inflammatory cytokines induced by Pam3CSK4 re-stimulation. Pam3CSK4 pre-treatment also down-regulated the signaling transduction of JNK, p38 and NF-κB induced by Pam3CSK4 re-stimulation. The activation of TLR1/2 induced a rapid and robust up-regulation of A20, suggesting that A20 may contribute to the induction of Pam3CSK4-tolerance. This hypothesis was proved by the observation that the over-expression of A20 by gene transfer down-regulated Pam3CSK4-induced inflammatory responses, and the down-regulation of A20 by RNA interference inhibited the induction of tolerance. Moreover, LPS induced a significant up-regulation of A20, which contributed to the induction of cross-tolerance between LPS and Pam3CSK4. A20 was also induced by the treatment of THP-1 cells with TNF-α and IL-1β. The pre-treatment with TNF-α and IL-1β partly down-regulated Pam3CSK4-induced activation of MAPKs. Furthermore, pharmacologic inhibition of GSK3 signaling down-regulated Pam3CSK4-induced A20 expression, up-regulated Pam3CSK4-induced inflammatory responses, and partly reversed Pam3CSK4 pre-treatment-induced tolerance, suggesting that GSK3 is involved in TLR1/2-induced tolerance by up-regulation of A20 expression. Taken together, these results indicated that A20 is a critical regulator for TLR1/2-induced pro-inflammatory responses. PMID:24489933

  15. The Thiamine-Pyrophosphate-Motif

    NASA Technical Reports Server (NTRS)

    Ciszak, Ewa; Dominiak, Paulina

    2004-01-01

    Thiamin pyrophosphate (TPP), a derivative of vitamin B1, is a cofactor for enzymes performing catalysis in pathways of energy production including the well known decarboxylation of a-keto acid dehydrogenases followed by transketolation. TPP-dependent enzymes constitute a structurally and functionally diverse group exhibiting multimeric subunit organization, multiple domains and two chemically equivalent catalytic centers. Annotation of functional TPP-dependcnt enzymes, therefore, has not been trivial due to low sequence similarity related to this complex organization. Our approach to analysis of structures of known TPP-dependent enzymes reveals for the first time features common to this group, which we have termed the TPP-motif. The TPP-motif consists of specific spatial arrangements of structural elements and their specific contacts to provide for a flip-flop, or alternate site, enzymatic mechanism of action. Analysis of structural elements entrained in the flip-flop action displayed by TPP-dependent enzymes reveals a novel definition of the common amino acid sequences. These sequences allow for annotation of TPP-dependent enzymes, thus advancing functional proteomics. Further details of three-dimensional structures of TPP-dependent enzymes will be discussed.

  16. Synthetic biology with RNA motifs.

    PubMed

    Saito, Hirohide; Inoue, Tan

    2009-02-01

    Structural motifs in naturally occurring RNAs and RNPs can be employed as new molecular parts for synthetic biology to facilitate the development of novel devices and systems that modulate cellular functions. In this review, we focus on the following: (i) experimental evolution techniques of RNA molecules in vitro and (ii) their applications for regulating gene expression systems in vivo. For experimental evolution, new artificial RNA aptamers and RNA enzymes (ribozymes) have been selected in vitro. These functional RNA molecules are likely to be applicable in the reprogramming of existing gene regulatory systems. Furthermore, they may be used for designing hypothetical RNA-based living systems in the so-called RNA world. For the regulation of gene expressions in living cells, the development of new riboswitches allows us to modulate the target gene expression in a tailor-made manner. Moreover, recently RNA-based synthetic genetic circuits have been reported by employing functional RNA molecules, expanding the repertory of synthetic biology with RNA motifs. PMID:18775792

  17. The Physical Abilities and Mobility Scale (PAMS): reliability and validity in children receiving inpatient brain injury rehabilitation

    PubMed Central

    Trovato, Melissa K.; Bradley, Elena; Slomine, Beth S.; Salorio, Cynthia F.; Christensen, James R.; Suskauer, Stacy J.

    2013-01-01

    Objective To investigate the psychometric properties of the Physical Abilities and Mobility Scale (PAMS) in children receiving inpatient rehabilitation for acquired brain injury. Design Admission and discharge PAMS item and total scores were evaluated. The Functional Independence Measure for Children (WeeFIM) was used as the criterion standard. A case study was used to illustrate the complementary nature of the PAMS and WeeFIM. Setting A single free-standing academically-affiliated pediatric rehabilitation hospital Participants 107 children aged two through eighteen years receiving inpatient rehabilitation for acquired brain injury between March 2009 and March 2012. 42 additional children treated during this time were excluded due to missing PAMS data. Interventions Not applicable Main Outcome Measures Internal consistency was evaluated using Cronbach alpha. Inter-rater reliability was evaluated through overall agreement, Pearson correlations, and intraclass correlations. Construct validity was examined through exploratory factor analysis. Criterion validity was explored through correlations of PAMS overall and factor scores with WeeFIM total and subscale scores. Sensitivity to recovery was examined using paired t tests examining differences between admission and discharge scores for each item and for the total score. Results Internal consistency and inter-rater reliability were high. Factor analysis revealed two factors: lower level skills and higher level mobility skills. Correlations with the WeeFIM ranged from moderate to very strong; total PAMS score most strongly correlated with the WeeFIM mobility subscore. Total PAMS score and each item score significantly increased between admission and discharge. Conclusions The PAMS is a reliable and valid measure of progress during inpatient rehabilitation for children with acquired brain injury. By capturing fine grain progress toward both lower level and higher level mobility skills, the PAMS complements the WeeFIM in

  18. DILIMOT: discovery of linear motifs in proteins.

    PubMed

    Neduva, Victor; Russell, Robert B

    2006-07-01

    Discovery of protein functional motifs is critical in modern biology. Small segments of 3-10 residues play critical roles in protein interactions, post-translational modifications and trafficking. DILIMOT (DIscovery of LInear MOTifs) is a server for the prediction of these short linear motifs within a set of proteins. Given a set of sequences sharing a common functional feature (e.g. interaction partner or localization) the method finds statistically over-represented motifs likely to be responsible for it. The input sequences are first passed through a set of filters to remove regions unlikely to contain instances of linear motifs. Motifs are then found in the remaining sequence and ranked according to a statistic that measure over-representation and conservation across homologues in related species. The results are displayed via a visual interface for easy perusal. The server is available at http://dilimot.embl.de. PMID:16845024

  19. Orientation and Dynamics of Synthetic Transbilayer Polypeptides Containing GpATM Dimerization Motifs

    PubMed Central

    McDonald, Mark C.; Booth, Valerie; Morrow, Michael R.

    2011-01-01

    Deuterium NMR spectroscopy was used to study how the positioning of a dimerization motif within a transbilayer polypeptide influences its orientation and dynamics in bilayers. Three polypeptide variants comprising glycophorin A transmembrane (GpATM) dimerization motifs incorporated into lysine-terminated poly-leucine-alanine helices were mixed into 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine multilamellar vesicles. The variants differed in orientation of the motif segment around the helix axis with respect to the peptide ends. Polypeptides were labeled with methyl-deuterated alanines at positions that were identically situated relative to the peptide ends (Ala-20 and Ala-22) and at two positions within the motif. An analysis of quadrupole splittings revealed similar tilts and orientations of the peptide ends for all three variants, suggesting that average orientations were dominated by interactions at the bilayer surface. For one variant, however, fast orientational fluctuations about the helix axis were significantly smaller. This may indicate some perturbation of peptide dynamics and conformation by interactions that are sensitive to the motif orientation relative to the peptide ends. For the variant that displayed distinct dynamics, one orientation consistent with observed splittings corresponded to the motif being situated such that its two glycines were particularly accessible to adjacent peptides. PMID:21281580

  20. Relationship between total Non-Methane Hydrocarbons (NMHC) and Speciated NMHCs by Photochemical Assessment Monitoring Station (PAMS)

    NASA Astrophysics Data System (ADS)

    Chen, S.; Ou Yang, C.; Chang, J.; Wang, J.

    2012-12-01

    Total NMHC observations were made in some of the EPA air quality stations (AQS) across Taiwan, along with measurements of ozone, CO, NOx, SO2 and PM10. This network is also complimented by another eight-station network, called photochemical assessment monitoring stations (PAMS), to provide hourly observations of 56 individual volatile organic compounds (VOCs). In this study, the relationship of the total NMHC and PAMS NMHC observations for the period of 2007-2011 at four sites were cross-examined. It was found that both the hourly mixing ratios and variations of the summed PAMS NMHC values were in excellent agreement with the total NMHC data, with the summed PAMS NMHC observations accounted for at least 80% of the total NMHC observations. However, when looking into the VOC emission database, the PAMS NMHC emissions only contributed 58% of the total NMHC emissions. This then leads to about 30% difference in the traditionally observed NMHCs and estimated emissions. The three-dimensional Eulerian air quality model (PAMS-AQM) was used to simulate both the total NMHC and individual PAMS NMHCs, which showed that the sum of the simulated PAMS NMHCs agreed well with the observed PAMS values. However, the modeled total VOC values were significantly higher than the observed total NMHC values, and such findings were consistent among all four stations. This and the above findings combine to suggest that the customarily labeled "total NMHC" reported by almost all air quality stations are underestimates by about 30%. This underestimate is rather uncertain for two reasons: One, both total NMHC and PAMS speciated NMHC measurements underestimate VOC levels in ambient air. Since both types of measurements use the same method of flame ionization detection, it is less sensitive to oxygen containing VOCs (OVOCs), e.g., aldehydes, esters, ketones, ether, acids, etc. than other VOCs. In contrast, the PAMS measurements only target 56 PAMS NMHCs although more directly, and OVOCs also are

  1. Autonomous NanoTechnology Swarm (ANTS) Prospecting Asteroid Mission (PAM), Asteroid Proximity Operations

    NASA Technical Reports Server (NTRS)

    Marr, Greg; Cooley, Steve; Roithmayr, Carlos; Kay-Bunnell, Linda; Williams, Trevor

    2004-01-01

    The Autonomous NanoTechnology Swarm (ANTS) is a generic mission architecture based on spatially distributed spacecraft, autonomous and redundant components, and hierarchical organization. The ANTS Prospecting Asteroid Mission (PAM) is an ANTS application which will nominally use a swarm of 1000 spacecraft. There would be 10 types of "specialists" with common spacecraft buses. There would be 10 subswarms of approximately 100 spacecraft each or approximately 10 of each specialist in each swarm. The ANTS PAM primary objective is the exploration of the asteroid belt in search of resources and material with astrobiologically relevant origins and signatures. The ANTS PAM spacecraft will nominally be released from a station in an Earth-Moon L1 libration point orbit, and they will use Solar sails for propulsion. The sail structure would be highly flexible, capable of changing morphology to change cross-section for capture of sunlight or to form effective "tip vanes" for attitude control. ANTS PAM sails would be capable of full to partial deployment, to change effective sail area and center of pressure, and thus allow attitude control. Results of analysis of a transfer trajectory from Earth to a sample target asteroid will be presented. ANTS PAM will require continuous coverage of different asteroid locations as close as one to two asteroid "diameters" from the surface of the asteroid for periods of science data collection during asteroid proximity operations. Hovering spacecraft could meet the science data collection objectives. The results of hovering analysis will be presented. There are locations for which hovering is not possible, for example on the illuminated side of the asteroid. For cases where hovering is not possible, the results of utilizing asteroid formations to orbit the asteroid and achieve the desired asteroid viewing will be presented for sample asteroids. The ability of ANTS PAM to reduce the area of the solar sail during asteroid proximity operations is

  2. Bridge and brick motifs in complex networks

    NASA Astrophysics Data System (ADS)

    Huang, Chung-Yuan; Sun, Chuen-Tsai; Cheng, Chia-Ying; Hsieh, Ji-Lung

    2007-04-01

    Acknowledging the expanding role of complex networks in numerous scientific contexts, we examine significant functional and topological differences between bridge and brick motifs for predicting network behaviors and functions. After observing similarities between social networks and their genetic, ecological, and engineering counterparts, we identify a larger number of brick motifs in social networks and bridge motifs in the other three types. We conclude that bridge and brick motif content analysis can assist researchers in understanding the small-world and clustering properties of network structures when investigating network functions and behaviors.

  3. 46 CFR 148.445 - Adjacent spaces.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 5 2013-10-01 2013-10-01 false Adjacent spaces. 148.445 Section 148.445 Shipping COAST... THAT REQUIRE SPECIAL HANDLING Additional Special Requirements § 148.445 Adjacent spaces. When... following requirements must be met: (a) Each space adjacent to a cargo hold must be ventilated by...

  4. 46 CFR 148.445 - Adjacent spaces.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 5 2014-10-01 2014-10-01 false Adjacent spaces. 148.445 Section 148.445 Shipping COAST... THAT REQUIRE SPECIAL HANDLING Additional Special Requirements § 148.445 Adjacent spaces. When... following requirements must be met: (a) Each space adjacent to a cargo hold must be ventilated by...

  5. 46 CFR 148.445 - Adjacent spaces.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 5 2012-10-01 2012-10-01 false Adjacent spaces. 148.445 Section 148.445 Shipping COAST... THAT REQUIRE SPECIAL HANDLING Additional Special Requirements § 148.445 Adjacent spaces. When... following requirements must be met: (a) Each space adjacent to a cargo hold must be ventilated by...

  6. 46 CFR 148.445 - Adjacent spaces.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 5 2011-10-01 2011-10-01 false Adjacent spaces. 148.445 Section 148.445 Shipping COAST... THAT REQUIRE SPECIAL HANDLING Additional Special Requirements § 148.445 Adjacent spaces. When... following requirements must be met: (a) Each space adjacent to a cargo hold must be ventilated by...

  7. A survey of motif finding Web tools for detecting binding site motifs in ChIP-Seq data.

    PubMed

    Tran, Ngoc Tam L; Huang, Chun-Hsi

    2014-01-01

    ChIP-Seq (chromatin immunoprecipitation sequencing) has provided the advantage for finding motifs as ChIP-Seq experiments narrow down the motif finding to binding site locations. Recent motif finding tools facilitate the motif detection by providing user-friendly Web interface. In this work, we reviewed nine motif finding Web tools that are capable for detecting binding site motifs in ChIP-Seq data. We showed each motif finding Web tool has its own advantages for detecting motifs that other tools may not discover. We recommended the users to use multiple motif finding Web tools that implement different algorithms for obtaining significant motifs, overlapping resemble motifs, and non-overlapping motifs. Finally, we provided our suggestions for future development of motif finding Web tool that better assists researchers for finding motifs in ChIP-Seq data. PMID:24555784

  8. Segmented silicon MZM for PAM-8 transmissions at 114 Gb/s with binary signaling.

    PubMed

    Simard, A D; Filion, B; Patel, D; Plant, D; LaRochelle, S

    2016-08-22

    We experimentally demonstrate PAM-8 generation from binary electrical signals driving a silicon multi-electrode Mach-Zehnder modulator acting as an optical digital-to-analog converter. Measured BER in back-to-back configuration is used to evaluate signal quality. We demonstrate 38 GBd PAM-8 transmission below the forward error correction (FEC) threshold using minimum mean square error (MMSE) equalization. The results show that modulators with segmented phase shifters can be advantageously used to eliminate the need for high bandwidth electronic digital-to-analog converters in the generation of multilevel signals. These modulators, that can be designed and fabricated with standard CMOS compatible tools and processes, are of high interest for short range high-speed data links. PMID:27557224

  9. Comparison of PAM Systems for Acoustic Monitoring and Further Risk Mitigation Application.

    PubMed

    Ludwig, Stefan; Kreimeyer, Roman; Knoll, Michaela

    2016-01-01

    We present results of the SIRENA 2011 research cruises conducted by the NATO Undersea Research Centre (NURC) and joined by the Research Department for Underwater Acoustics and Geophysics (FWG), Bundeswehr Technical Centre (WTD 71) and the Universities of Kiel and Pavia. The cruises were carried out in the Ligurian Sea. The main aim of the FWG was to test and evaluate the newly developed towed hydrophone array as a passive acoustic monitoring (PAM) tool for risk mitigation applications. The system was compared with the PAM equipment used by the other participating institutions. Recorded sounds were used to improve an automatic acoustic classifier for marine mammals, and validated acoustic detections by observers were compared with the results of the classifier. PMID:26611016

  10. Region-of-interest breast images with the Twente Photoacoustic Mammoscope (PAM)

    NASA Astrophysics Data System (ADS)

    Manohar, Srirang; Vaartjes, Sanne E.; van Hespen, Johan G. C.; Klaase, Joost M.; van den Engh, Frank M.; The, Andy K. H.; Steenbergen, Wiendelt; van Leeuwen, Ton G.

    2007-02-01

    The Twente Photoacoustic Mammoscope (PAM) is based on generating laser-induced ultrasound from absorbing structures in the breast. The heart of the instrument is a flat PVDF based detector matrix comprising 590 active elements. The exciting source is an Nd:YAG laser operating at 1064 nm with 5 ns pulses. The instrument is built around a hospital bed. A study protocol was designed to explore the feasibility of using the photoacoustic technique as embodied in PAM to detect cancer in the breasts of patients with suspect/symptomatic breasts. The protocol was approved by a Medical Ethics testing committee and the instrument approved for laser and electrical safety. The protocol was executed at the Medisch Spectrum Twente by using the mammoscope to obtain photoacoustic region-of-interest (ROI) images of the suspect/symptomatic breasts. We report on one case and compare the photoacoustic images obtained with x-ray mammograms and ultrasound images.

  11. Optical coherence photoacoustic microscopy (OC-PAM) with an intensity-modulated continuous-wave broadband light source

    NASA Astrophysics Data System (ADS)

    Liu, Xiaojing; Wen, Rong; Li, Yiwen; Jiao, Shuliang

    2016-06-01

    We developed an optical coherence photoacoustic microscopy system using an intensity-modulated continuous-wave superluminescent diode with a center wavelength of 840 nm. The system can accomplish optical coherence tomography (OCT) and photoacoustic microscopy (PAM) simultaneously. Compared to the system with a pulsed light source, this system is able to achieve OCT imaging with quality as high as conventional spectral-domain OCT. Since both of the OCT and PAM images are generated from the same group of photons, they are intrinsically registered in the lateral directions. The system was tested for multimodal imaging the vasculature of mouse ear in vivo by using gold nanorods as contrast agent for PAM, as well as excised porcine eyes ex vivo. The OCT and PAM images showed complimentary information of the sample.

  12. OFDM and PAM comparison using a high baudrate low resolution IM/DD interface for 400G Ethernet access.

    PubMed

    André, Nuno Sequeira; Louchet, Hadrien; Filsinger, Volker; Hansen, Erik; Richter, André

    2016-05-30

    We compare OFDM and PAM for 400G Ethernet based on a 3-bit high baudrate IM/DD interface at 1550nm. We demonstrate 27Gb/s and 32Gb/s transmission over 10km SSMF using OFDM and PAM respectively. We show that capacity can be improved through adaptation/equalization to achieve 42Gb/s and 64Gb/s for OFDM and PAM respectively. Experimental results are used to create realistic simulations to extrapolate the performance of both modulation formats under varied conditions. For the considered interface we found that PAM has the best performance, OFDM is impaired by quantization noise. When the resolution limitation is relaxed, OFDM shows better performance. PMID:27410115

  13. Large-field-of-view laser-scanning OR-PAM using a fibre optic sensor

    NASA Astrophysics Data System (ADS)

    Allen, T. J.; Zhang, E.; Beard, P. C.

    2015-03-01

    Laser-Scanning-Optical-Resolution Photoacoustic Microscopy (LSOR-PAM) requires an ultrasound detector with a low noise equivalent pressure (NEP) and a large angular detection aperture in order to image a large field of view (FOV). It is however challenging to meet these requirements when using piezoelectric receivers since using a small sensing element size (<100μm) in order to achieve a large angular detection aperture will inevitability reduce the sensitivity of the detector as it scales with decreasing element size. Fibre optic ultrasound sensors based on a Fabry Perot cavity do not suffer from this limitation and can provide high detection sensitivity (NEP<0.1kPa over a 20 MHz measurement bandwidth) with a large angular detection aperture due to their small active element size (~10μm). A LSOR-PAM system was developed and combined with this type of fibre optic ultrasound sensor. A set of phantom studies were undertaken. The first study demonstrated that a high resolution image over a large field of view (Ø11mm) could be obtained with a sampledetector separation of only 1.6mm. In the second study, a 12μm diameter tube filled with methylene blue whose absorption coefficient was similar to that of blood was visualised demonstrating that the fibre optic sensor could provide sufficient SNR for in-vivo microvascular OR-PAM imaging. These preliminary results suggest that the fibre optic sensor has the potential to outperform piezoelectric detectors for Laser-Scanning Optical Resolution Photoacoustic Microscopy (LSOR-PAM).

  14. TP53 Mutational Analysis Enhances the Prognostic Accuracy of IHC4 and PAM50 Assays

    PubMed Central

    Lin, Ching-Hung; Chen, I-Chiun; Huang, Chiun-Sheng; Hu, Fu-Chang; Kuo, Wen-Hung; Kuo, Kuan-Ting; Wang, Chung-Chieh; Wu, Pei-Fang; Chang, Dwan-Ying; Wang, Ming-Yang; Chang, Chin-Hao; Chen, Wei-Wu; Lu, Yen-Shen; Cheng, Ann-Lii

    2015-01-01

    IHC4 and PAM50 assays have been shown to provide additional prognostic information for patients with early breast cancer. We evaluated whether incorporating TP53 mutation analysis can further enhance their prognostic accuracy. We examined TP53 mutation and the IHC4 score in tumors of 605 patients diagnosed with stage I–III breast cancer at National Taiwan University Hospital (the NTUH cohort). We obtained information regarding TP53 mutation and PAM50 subtypes in 699 tumors from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) cohort. We found that TP53 mutation was significantly associated with high-risk IHC4 group and with luminal B, HER2-enriched, and basal-like subtypes. Despite the strong associations, TP53 mutation independently predicted shorter relapse-free survival (hazard ratio [HR] = 1.63, P = 0.007) in the NTUH cohort and shorter breast cancer-specific survival (HR = 2.35, P = <0.001) in the METABRIC cohort. TP53 mutational analysis added significant prognostic information in addition to the IHC4 score (∆ LR-χ2 = 8.61, P = 0.002) in the NTUH cohort and the PAM50 subtypes (∆ LR-χ2 = 18.9, P = <0.001) in the METABRIC cohort. We conclude that incorporating TP53 mutation analysis can enhance the prognostic accuracy of the IHC4 and PAM50 assays. PMID:26671300

  15. PAM4 Immunoassay Alone and in Combination with CA19-9 for the Detection of Pancreatic Adenocarcinoma

    PubMed Central

    Gold, David V.; Gaedcke, Jochen; Ghadimi, B. Michael; Goggins, Michael; Hruban, Ralph H.; Liu, Mengling; Newsome, Guy; Goldenberg, David M.

    2012-01-01

    Background Monoclonal antibody PAM4 has high specificity for pancreatic ductal adenocarcinoma (PDAC), as well as its precursor lesions, but is not reactive with normal and benign pancreatic tissues. Our purpose was to evaluate a PAM4-based serum-immunoassay alone, and in combination with the CA19-9 assay, for the detection of PDAC with particular attention to early-stage disease. Methods Sera from patients with confirmed PDAC (N=298), other cancers (N=99), benign disease of the pancreas (N=120), and healthy adults (N=79) were evaluated by specific enzyme-immunoassay for concentration of PAM4 and CA19-9 antigen levels by blinded analyses. All tests for statistical significance were two-sided. Results Overall sensitivity for PAM4 detection of PDAC was 76%, with 64% of stage-1 patients also identified. The detection rate was considerably higher (85%) for advanced disease. The assay showed high specificity compared to benign pancreatic disease (85%), with a positive likelihood ratio (+LR) of 4.93. CA19-9 provided an overall sensitivity of 77%, and was positive in 58% of patients with stage-1 disease; however, specificity was significantly lower for CA19-9 (68%) with a +LR=2.85 (P=0.026 compared to PAM4). Importantly, a combined PAM4/CA19-9 assay demonstrated an improved sensitivity (84%) for overall detection of PDAC without significant loss of specificity (82%), as compared to either arm alone. Conclusions The PAM4-immunoassay identified approximately two-thirds of stage-1 PDAC patients with high discriminatory power with respect to benign, non-neoplastic pancreatic disease. These results provide a rationale for testing patient groups considered at high-risk for PDAC with a combined PAM4/CA19-9 biomarker assay for detection of early-stage PDAC. PMID:22898932

  16. Breast imaging using the Twente photoacoustic mammoscope (PAM): new clinical measurements

    NASA Astrophysics Data System (ADS)

    Heijblom, Michelle; Piras, Daniele; Ten Tije, Ellen; Xia, Wenfeng; van Hespen, Johan; Klaase, Joost; van den Engh, Frank; van Leeuwen, Ton; Steenbergen, Wiendelt; Manohar, Srirang

    2011-07-01

    Worldwide, yearly about 450,000 women die from the consequences of breast cancer. Current imaging modalities are not optimal in discriminating benign from malignant tissue. Visualizing the malignancy-associated increased hemoglobin concentration might significantly improve early diagnosis of breast cancer. Since photoacoustic imaging can visualize hemoglobin in tissue with optical contrast and ultrasound-like resolution, it is potentially an ideal method for early breast cancer imaging. The Twente Photoacoustic Mammoscope (PAM) has been developed specifically for breast imaging. Recently, a large clinical study has been started in the Medisch Spectrum Twente in Oldenzaal using PAM. In PAM, the breast is slightly compressed between a window for laser light illumination and a flat array ultrasound detector. The measurements are performed using a Q-switched Nd:YAG laser, pulsed at 1064 nm and a 1 MHz unfocused ultrasound detector array. Three-dimensional data are reconstructed using a delay and sum reconstruction algorithm. Those reconstructed images are compared with conventional imaging and histopathology. In the first phase of the study 12 patients with a malignant lesion and 2 patients with a benign cyst have been measured. The results are used to guide developments in photoacoustic mammography in order to pave the way towards an optimal technique for early diagnosis of breast cancer.

  17. FRAP and Photoconversion in Multiple Arbitrary Regions of Interest Using a Programmable Array Microscope (PAM)

    PubMed Central

    Hagen, Guy M.; Caarls, Wouter; Lidke, Keith A.; de Vries, Anthony H. B.; Fritsch, Cornelia; Barisas, B. George; Arndt-Jovin, Donna J.; Jovin, Thomas M.

    2011-01-01

    Photomanipulation (photobleaching, photoactivation, or photoconversion) is an essential tool in fluorescence microscopy. Fluorescence recovery after photobleaching (FRAP) is commonly used for the determination of lateral diffusion constants of membrane proteins, and can be conveniently implemented in confocal laser scanning microscopy (CLSM). Such determinations provide important information on molecular dynamics in live cells. However, the CLSM platform is inherently limited for FRAP because of its inflexible raster (spot) scanning format. We have implemented FRAP and photoactivation protocols using structured illumination and detection in a programmable array microscope (PAM). The patterns are arbitrary in number and shape, dynamic and adjustable to and by the sample characteristics. We have used multi-spot PAM-FRAP to measure the lateral diffusion of the erbB3 (HER3) receptor tyrosine kinase labeled by fusion with mCitrine on untreated cells and after treatment with reagents that perturb the cytoskeleton or plasma membrane or activate co-expressed erbB1 (HER1, the EGF receptor EGFR). We also show the versatility of the PAM for photoactivation in arbitrary regions of interest, in cells expressing erbB3 fused with the photoconvertible fluorescent protein dronpa. PMID:19208387

  18. Discovery of ML326: the first sub-micromolar, selective M5 PAM

    PubMed Central

    Gentry, Patirck R.; Bridges, Thomas M.; Lamasal, Atin; Vinson, Paige N.; Smith, Emery; Chase, Peter; Hodder, Peter S.; Engers, Julie L.; Niswender, Colleen M.; Daniels, J. Scott; Conn, P. Jeffrey; Wood, Michael R.; Lindsley, Craig W.

    2013-01-01

    This letter describes the further chemical optimization of the M5 PAM MLPCN probes ML129 and ML172. A multi-dimensional iterative parallel synthesis effort quickly explored isatin replacements and a number of southern heterobiaryl variations with no improvement over ML129 and ML172. An HTS campaign identified several weak M5 PAMs (M5 EC50 >10 μM) with a structurally related isatin core that possessed a southern phenethyl ether linkage. While SAR within the HTS series was very shallow and unable to be optimized, grafting the phenethyl ether linkage onto the ML129/ML172 cores led to the first sub-micromolar M5 PAM, ML326 (VU0467903), (human and rat M5 EC50s of 409 nM and 480 nM, respectively) with excellent mAChR selectivity (M1-M4 EC50s <30 μM) and a robust 20-fold leftward shift of the ACh CRC. PMID:23562060

  19. Solar Radiation Stress in Natural Acidophilic Biofilms of Euglena mutabilis Revealed by Metatranscriptomics and PAM Fluorometry.

    PubMed

    Puente-Sánchez, Fernando; Olsson, Sanna; Gómez-Rodriguez, Manuel; Souza-Egipsy, Virginia; Altamirano-Jeschke, Maria; Amils, Ricardo; Parro, Victor; Aguilera, Angeles

    2016-02-01

    The daily photosynthetic performance of a natural biofilm of the extreme acidophilic Euglena mutabilis from Río Tinto (SW, Spain) under full solar radiation was analyzed by means of pulse amplitude-modulated (PAM) fluorescence measurements and metatrascriptomic analysis. Natural E. mutabilis biofilms undergo large-scale transcriptomic reprogramming during midday due to a dynamic photoinhibition and solar radiation stress. Photoinhibition is due to UV radiation and not to light intensity, as revealed by PAM fluorometry analysis. In order to minimize the negative effects of solar radiation, our data supports the presence of a circadian rhythm in this euglenophyte that increases their opportunity to survive. Differential gene expression throughout the day (at 12:00, 20:00 and night) was monitored by massive Illumina parallel sequencing of metatranscriptomic libraries. The transcription pattern was altered in genes involved in Photosystem II stability and repair, UV damaged DNA repair, non-photochemical quenching and oxidative stress, supporting the photoinhibition detected by PAM fluorometry at midday. PMID:26827143

  20. Temporal motifs in time-dependent networks

    NASA Astrophysics Data System (ADS)

    Kovanen, Lauri; Karsai, Márton; Kaski, Kimmo; Kertész, János; Saramäki, Jari

    2011-11-01

    Temporal networks are commonly used to represent systems where connections between elements are active only for restricted periods of time, such as telecommunication, neural signal processing, biochemical reaction and human social interaction networks. We introduce the framework of temporal motifs to study the mesoscale topological-temporal structure of temporal networks in which the events of nodes do not overlap in time. Temporal motifs are classes of similar event sequences, where the similarity refers not only to topology but also to the temporal order of the events. We provide a mapping from event sequences to coloured directed graphs that enables an efficient algorithm for identifying temporal motifs. We discuss some aspects of temporal motifs, including causality and null models, and present basic statistics of temporal motifs in a large mobile call network.

  1. Sampling Motif-Constrained Ensembles of Networks

    NASA Astrophysics Data System (ADS)

    Fischer, Rico; Leitão, Jorge C.; Peixoto, Tiago P.; Altmann, Eduardo G.

    2015-10-01

    The statistical significance of network properties is conditioned on null models which satisfy specified properties but that are otherwise random. Exponential random graph models are a principled theoretical framework to generate such constrained ensembles, but which often fail in practice, either due to model inconsistency or due to the impossibility to sample networks from them. These problems affect the important case of networks with prescribed clustering coefficient or number of small connected subgraphs (motifs). In this Letter we use the Wang-Landau method to obtain a multicanonical sampling that overcomes both these problems. We sample, in polynomial time, networks with arbitrary degree sequences from ensembles with imposed motifs counts. Applying this method to social networks, we investigate the relation between transitivity and homophily, and we quantify the correlation between different types of motifs, finding that single motifs can explain up to 60% of the variation of motif profiles.

  2. Characterization of biopolymeric flocculant (pectin) and organic synthetic flocculant (PAM): a comparative study on treatment and optimization in kaolin suspension.

    PubMed

    Ho, Y C; Norli, I; Alkarkhi, Abbas F M; Morad, N

    2010-02-01

    Polyacrylamide (PAM), a commonly used organic synthetic flocculant, is known to have high reduction in turbidity treatment. However, PAM is not readily degradable. In this paper, pectin as a biopolymeric flocculant is used. The objectives are (i) to determine the characteristics of both flocculants (ii) to optimize the treatment processes of both flocculants in synthetic turbid waste water. The results obtained indicated that pectin has a lower average molecular weight at 1.63 x 10(5) and PAM at 6.00 x 10(7). However, the thermal degradation results showed that the onset temperature for pectin is at 165.58 degrees C, while the highest onset temperature obtained for PAM is at 235.39 degrees C. The optimum treatment conditions for the biopolymeric flocculant for flocculating activity was at pH 3, cation concentration at 0.55 mM, and pectin concentration at 3 mg/L. In contrast, PAM was at pH 4, cation concentration >0.05 mM and PAM concentration between 13 and 30 mg/L. PMID:19854044

  3. The pam1 gene is required for meiotic bouquet formation and efficient homologous synapsis in maize (Zea mays L.).

    PubMed Central

    Golubovskaya, Inna N; Harper, Lisa C; Pawlowski, Wojciech P; Schichnes, Denise; Cande, W Zacheus

    2002-01-01

    The clustering of telomeres on the nuclear envelope (NE) during meiotic prophase to form the bouquet arrangement of chromosomes may facilitate homologous chromosome synapsis. The pam1 (plural abnormalities of meiosis 1) gene is the first maize gene that appears to be required for telomere clustering, and homologous synapsis is impaired in pam1. Telomere clustering on the NE is arrested or delayed at an intermediate stage in pam1. Telomeres associate with the NE during the leptotene-zygotene transition but cluster slowly if at all as meiosis proceeds. Intermediate stages in telomere clustering including miniclusters are observed in pam1 but not in wild-type meiocytes. The tight bouquet normally seen at zygotene is a rare event. In contrast, the polarization of centromeres vs. telomeres in the nucleus at the leptotene-zygotene transition is the same in mutant and wild-type cells. Defects in homologous chromosome synapsis include incomplete synapsis, nonhomologous synapsis, and unresolved interlocks. However, the number of RAD51 foci on chromosomes in pam1 is similar to that of wild type. We suggest that the defects in homologous synapsis and the retardation of prophase I arise from the irregularity of telomere clustering and propose that pam1 is involved in the control of bouquet formation and downstream meiotic prophase I events. PMID:12524364

  4. SURVEY AND SUMMARY: Unusual DNA duplex and hairpin motifs

    PubMed Central

    Chou, Shan-Ho; Chin, Ko-Hsin; Wang, Andrew H.-J.

    2003-01-01

    Single-stranded DNA or double-stranded DNA has the potential to adopt a wide variety of unusual duplex and hairpin motifs in the presence (trans) or absence (cis) of ligands. Several principles for the formation of those unusual structures have been established through the observation of a number of recurring structural motifs associated with different sequences. These include: (i) internal loops of consecutive mismatches can occur in a B-DNA duplex when sheared base pairs are adjacent to each other to confer extensive cross- and intra-strand base stacking; (ii) interdigitated (zipper-like) duplex structures form instead when sheared G·A base pairs are separated by one or two pairs of purine·purine mismatches; (iii) stacking is not restricted to base, deoxyribose also exhibits the potential to do so; (iv) canonical G·C or A·T base pairs are flexible enough to exhibit considerable changes from the regular H-bonded conformation. The paired bases become stacked when bracketed by sheared G·A base pairs, or become extruded out and perpendicular to their neighboring bases in the presence of interacting drugs; (v) the purine-rich and pyrimidine-rich loop structures are notably different in nature. The purine-rich loops form compact triloop structures closed by a sheared G·A, A·A, A·C or sheared-like Ganti·Csyn base pair that is stacked by a single residue. On the other hand, the pyrimidine-rich loops with a thymidine in the first position exhibit no base pairing but are characterized by the folding of the thymidine residue into the minor groove to form a compact loop structure. Identification of such diverse duplex or hairpin motifs greatly enlarges the repertoire for unusual DNA structural formation. PMID:12736295

  5. Stochastic motif extraction using hidden Markov model

    SciTech Connect

    Fujiwara, Yukiko; Asogawa, Minoru; Konagaya, Akihiko

    1994-12-31

    In this paper, we study the application of an HMM (hidden Markov model) to the problem of representing protein sequences by a stochastic motif. A stochastic protein motif represents the small segments of protein sequences that have a certain function or structure. The stochastic motif, represented by an HMM, has conditional probabilities to deal with the stochastic nature of the motif. This HMM directive reflects the characteristics of the motif, such as a protein periodical structure or grouping. In order to obtain the optimal HMM, we developed the {open_quotes}iterative duplication method{close_quotes} for HMM topology learning. It starts from a small fully-connected network and iterates the network generation and parameter optimization until it achieves sufficient discrimination accuracy. Using this method, we obtained an HMM for a leucine zipper motif. Compared to the accuracy of a symbolic pattern representation with accuracy of 14.8 percent, an HMM achieved 79.3 percent in prediction. Additionally, the method can obtain an HMM for various types of zinc finger motifs, and it might separate the mixed data. We demonstrated that this approach is applicable to the validation of the protein databases; a constructed HMM b as indicated that one protein sequence annotated as {open_quotes}lencine-zipper like sequence{close_quotes} in the database is quite different from other leucine-zipper sequences in terms of likelihood, and we found this discrimination is plausible.

  6. Automated Motif Discovery from Glycan Array Data

    PubMed Central

    Cholleti, Sharath R.; Agravat, Sanjay; Morris, Tim; Saltz, Joel H.; Song, Xuezheng

    2012-01-01

    Abstract Assessing interactions of a glycan-binding protein (GBP) or lectin with glycans on a microarray generates large datasets, making it difficult to identify a glycan structural motif or determinant associated with the highest apparent binding strength of the GBP. We have developed a computational method, termed GlycanMotifMiner, that uses the relative binding of a GBP with glycans within a glycan microarray to automatically reveal the glycan structural motifs recognized by a GBP. We implemented the software with a web-based graphical interface for users to explore and visualize the discovered motifs. The utility of GlycanMotifMiner was determined using five plant lectins, SNA, HPA, PNA, Con A, and UEA-I. Data from the analyses of the lectins at different protein concentrations were processed to rank the glycans based on their relative binding strengths. The motifs, defined as glycan substructures that exist in a large number of the bound glycans and few non-bound glycans, were then discovered by our algorithm and displayed in a web-based graphical user interface (http://glycanmotifminer.emory.edu). The information is used in defining the glycan-binding specificity of GBPs. The results were compared to the known glycan specificities of these lectins generated by manual methods. A more complex analysis was also carried out using glycan microarray data obtained for a recombinant form of human galectin-8. Results for all of these lectins show that GlycanMotifMiner identified the major motifs known in the literature along with some unexpected novel binding motifs. PMID:22877213

  7. Automated motif discovery from glycan array data.

    PubMed

    Cholleti, Sharath R; Agravat, Sanjay; Morris, Tim; Saltz, Joel H; Song, Xuezheng; Cummings, Richard D; Smith, David F

    2012-10-01

    Assessing interactions of a glycan-binding protein (GBP) or lectin with glycans on a microarray generates large datasets, making it difficult to identify a glycan structural motif or determinant associated with the highest apparent binding strength of the GBP. We have developed a computational method, termed GlycanMotifMiner, that uses the relative binding of a GBP with glycans within a glycan microarray to automatically reveal the glycan structural motifs recognized by a GBP. We implemented the software with a web-based graphical interface for users to explore and visualize the discovered motifs. The utility of GlycanMotifMiner was determined using five plant lectins, SNA, HPA, PNA, Con A, and UEA-I. Data from the analyses of the lectins at different protein concentrations were processed to rank the glycans based on their relative binding strengths. The motifs, defined as glycan substructures that exist in a large number of the bound glycans and few non-bound glycans, were then discovered by our algorithm and displayed in a web-based graphical user interface ( http://glycanmotifminer.emory.edu ). The information is used in defining the glycan-binding specificity of GBPs. The results were compared to the known glycan specificities of these lectins generated by manual methods. A more complex analysis was also carried out using glycan microarray data obtained for a recombinant form of human galectin-8. Results for all of these lectins show that GlycanMotifMiner identified the major motifs known in the literature along with some unexpected novel binding motifs. PMID:22877213

  8. Theme and variations: evolutionary diversification of the HET-s functional amyloid motif

    PubMed Central

    Daskalov, Asen; Dyrka, Witold; Saupe, Sven J.

    2015-01-01

    In mammals and fungi, Nod-like receptors (NLR) activate downstream cell death execution proteins by a prion-like mechanism. In Podospora anserina, the NWD2 NLR activates the HET-S Helo-domain pore-forming protein by converting its prion-forming domain into a characteristic β-solenoid amyloid fold. The amyloid forming region of HET-S/s comprises two repetitions of a 21 amino acid motif. Herein, we systematically analyze the sequences of C-terminal regions of fungal HeLo and HeLo-like domain proteins to identify HET-s-related amyloid motifs (HRAM). We now identify four novel HRAM subfamilies in addition to the canonical HET-S/s subfamily. These novel motifs share the pseudo-repeat structure of HET-S/s and a specific pattern of distribution of hydrophobic and polar residues. Sequence co-variance analyses predict parallel in-register β-stacking of the two repeats and residue-residue interactions compatible with the β-solenoid fold. As described for HET-S, most genes encoding the HeLo proteins are adjacent to genes encoding NLRs also displaying HRAMs. The motifs of the NLRs are similar to those of their cognate HeLo-domain protein, indicating concerted evolution between repeats. This study shows that HET-s-related amyloid motifs are more common than anticipated and that they have diversified into discrete subfamilies that apparently share a common overall fold. PMID:26219477

  9. RSAT peak-motifs: motif analysis in full-size ChIP-seq datasets.

    PubMed

    Thomas-Chollier, Morgane; Herrmann, Carl; Defrance, Matthieu; Sand, Olivier; Thieffry, Denis; van Helden, Jacques

    2012-02-01

    ChIP-seq is increasingly used to characterize transcription factor binding and chromatin marks at a genomic scale. Various tools are now available to extract binding motifs from peak data sets. However, most approaches are only available as command-line programs, or via a website but with size restrictions. We present peak-motifs, a computational pipeline that discovers motifs in peak sequences, compares them with databases, exports putative binding sites for visualization in the UCSC genome browser and generates an extensive report suited for both naive and expert users. It relies on time- and memory-efficient algorithms enabling the treatment of several thousand peaks within minutes. Regarding time efficiency, peak-motifs outperforms all comparable tools by several orders of magnitude. We demonstrate its accuracy by analyzing data sets ranging from 4000 to 1,28,000 peaks for 12 embryonic stem cell-specific transcription factors. In all cases, the program finds the expected motifs and returns additional motifs potentially bound by cofactors. We further apply peak-motifs to discover tissue-specific motifs in peak collections for the p300 transcriptional co-activator. To our knowledge, peak-motifs is the only tool that performs a complete motif analysis and offers a user-friendly web interface without any restriction on sequence size or number of peaks. PMID:22156162

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

    PubMed Central

    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. CodingMotif: exact determination of overrepresented nucleotide motifs in coding sequences

    PubMed Central

    2012-01-01

    Background It has been increasingly appreciated that coding sequences harbor regulatory sequence motifs in addition to encoding for protein. These sequence motifs are expected to be overrepresented in nucleotide sequences bound by a common protein or small RNA. However, detecting overrepresented motifs has been difficult because of interference by constraints at the protein level. Sampling-based approaches to solve this problem based on codon-shuffling have been limited to exploring only an infinitesimal fraction of the sequence space and by their use of parametric approximations. Results We present a novel O(N(log N)2)-time algorithm, CodingMotif, to identify nucleotide-level motifs of unusual copy number in protein-coding regions. Using a new dynamic programming algorithm we are able to exhaustively calculate the distribution of the number of occurrences of a motif over all possible coding sequences that encode the same amino acid sequence, given a background model for codon usage and dinucleotide biases. Our method takes advantage of the sparseness of loci where a given motif can occur, greatly speeding up the required convolution calculations. Knowledge of the distribution allows one to assess the exact non-parametric p-value of whether a given motif is over- or under- represented. We demonstrate that our method identifies known functional motifs more accurately than sampling and parametric-based approaches in a variety of coding datasets of various size, including ChIP-seq data for the transcription factors NRSF and GABP. Conclusions CodingMotif provides a theoretically and empirically-demonstrated advance for the detection of motifs overrepresented in coding sequences. We expect CodingMotif to be useful for identifying motifs in functional genomic datasets such as DNA-protein binding, RNA-protein binding, or microRNA-RNA binding within coding regions. A software implementation is available at http://bioinformatics.bc.edu/chuanglab/codingmotif.tar PMID

  12. Scaling single-wavelength optical interconnects to 180 Gb/s with PAM-M and pulse shaping

    NASA Astrophysics Data System (ADS)

    Dris, Stefanos; Bakopoulos, Paraskevas; Argyris, Nikolaos; Spatharakis, Christos; Avramopoulos, Hercules

    2016-03-01

    Faced with surging datacenter traffic demand, system designers are turning to multi-level optical modulation with direct detection as the means of reaching 100 Gb/s in a single optical lane; a further upgrade to 400 Gb/s is envisaged through wavelength-multiplexing of multiple 100 Gb/s strands. In terms of modulation formats, PAM-4 and PAM-8 are considered the front-runners, striking a good balance between bandwidth-efficiency and implementation complexity. In addition, the emergence of energy-efficient, high-speed CMOS digital-to-analog converters (DACs) opens up new possibilities: Spectral shaping through digital filtering will allow squeezing even more data through low-cost, low-bandwidth electro-optic components. In this work we demonstrate an optical interconnect based on an EAM that is driven directly with sub-volt electrical swing by a 65 GSa/s arbitrary waveform generator (AWG). Low-voltage drive is particularly attractive since it allows direct interfacing with the switch/server ASIC, eliminating the need for dedicated, power-hungry and expensive electrical drivers. Single-wavelength throughputs of 180 and 120 Gb/s are experimentally demonstrated with 60 Gbaud optical PAM-8 and PAM-4 respectively. Successful transmission over 1250 m SMF is achieved with direct-detection, using linear equalization via offline digital signal processing in order to overcome the strong bandwidth limitation of the overall link (~20 GHz). The suitability of Nyquist pulse shaping for optical interconnects is also investigated experimentally with PAM-4 and PAM-8, at a lower symbol rate of 40 Gbaud (limited by the sampling rate of the AWG). To the best of our knowledge, the rates achieved are the highest ever using optical PAM-M formats.

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

    NASA Astrophysics Data System (ADS)

    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.

  14. DNA Motif Databases and Their Uses.

    PubMed

    Stormo, Gary D

    2015-01-01

    Transcription factors (TFs) recognize and bind to specific DNA sequences. The specificity of a TF is usually represented as a position weight matrix (PWM). Several databases of DNA motifs exist and are used in biological research to address important biological questions. This overview describes PWMs and some of the most commonly used motif databases, as well as a few of their common applications. PMID:26334922

  15. The PAM-1 aminopeptidase regulates centrosome positioning to ensure anterior-posterior axis specification in one-cell C. elegans embryos

    PubMed Central

    Fortin, Samantha M.; Marshall, Sara L.; Jaeger, Eva C.; Greene, Pauline E.; Brady, Lauren K.; Isaac, R. Elwyn; Schrandt, Jennifer C.; Brooks, Darren R.; Lyczak, Rebecca

    2010-01-01

    In the one-cell Caenorhabditis elegans embryo, the anterior-posterior (A-P) axis is established when the sperm donated centrosome contacts the posterior cortex. While this contact appears to be essential for axis polarization, little is known about the mechanisms governing centrosome positioning during this process. pam-1 encodes a puromycin sensitive aminopeptidase that regulates centrosome positioning in the early embryo. Previously we showed that pam-1 mutants fail to polarize the A-P axis. Here we show that PAM-1 can be found in mature sperm and in cytoplasm throughout early embryogenesis where it concentrates around mitotic centrosomes and chromosomes. We provide further evidence that PAM-1 acts early in the polarization process by showing that PAR-1 and PAR-6 do not localize appropriately in pam-1 mutants. Additionally, we tested the hypothesis that PAM-1’s role in polarity establishment is to ensure centrosome contact with the posterior cortex. We inactivated the microtubule motor dynein, DHC-1, in pam-1 mutants, in an attempt to prevent centrosome movement from the cortex and restore anterior-posterior polarity. When this was done, the aberrant centrosome movements of pam-1 mutants were not observed and anterior-posterior polarity was properly established, with proper localization of cortical and cytoplasmic determinants. We conclude that PAM-1’s role in axis polarization is to prevent premature movement of the centrosome from the posterior cortex, ensuring proper axis establishment in the embryo. PMID:20599902

  16. Resolving the contribution of the uncoupled phycobilisomes to cyanobacterial pulse-amplitude modulated (PAM) fluorometry signals.

    PubMed

    Acuña, Alonso M; Snellenburg, Joris J; Gwizdala, Michal; Kirilovsky, Diana; van Grondelle, Rienk; van Stokkum, Ivo H M

    2016-01-01

    Pulse-amplitude modulated (PAM) fluorometry is extensively used to characterize photosynthetic organisms on the slow time-scale (1-1000 s). The saturation pulse method allows determination of the quantum yields of maximal (F(M)) and minimal fluorescence (F(0)), parameters related to the activity of the photosynthetic apparatus. Also, when the sample undergoes a certain light treatment during the measurement, the fluorescence quantum yields of the unquenched and the quenched states can be determined. In the case of cyanobacteria, however, the recorded fluorescence does not exclusively stem from the chlorophyll a in photosystem II (PSII). The phycobilins, the pigments of the cyanobacterial light-harvesting complexes, the phycobilisomes (PB), also contribute to the PAM signal, and therefore, F(0) and F(M) are no longer related to PSII only. We present a functional model that takes into account the presence of several fluorescent species whose concentrations can be resolved provided their fluorescence quantum yields are known. Data analysis of PAM measurements on in vivo cells of our model organism Synechocystis PCC6803 is discussed. Three different components are found necessary to fit the data: uncoupled PB (PB(free)), PB-PSII complexes, and free PSI. The free PSII contribution was negligible. The PB(free) contribution substantially increased in the mutants that lack the core terminal emitter subunits allophycocyanin D or allophycocyanin F. A positive correlation was found between the amount of PB(free) and the rate constants describing the binding of the activated orange carotenoid protein to PB, responsible for non-photochemical quenching. PMID:25893897

  17. Alpha7 nicotinic acetylcholine receptor agonists and PAMs as adjunctive treatment in schizophrenia. An experimental study.

    PubMed

    Marcus, Monica M; Björkholm, Carl; Malmerfelt, Anna; Möller, Annie; Påhlsson, Ninni; Konradsson-Geuken, Åsa; Feltmann, Kristin; Jardemark, Kent; Schilström, Björn; Svensson, Torgny H

    2016-09-01

    Nicotine has been found to improve cognition and reduce negative symptoms in schizophrenia and a genetic and pathophysiological link between the α7 nicotinic acetylcholine receptors (nAChRs) and schizophrenia has been demonstrated. Therefore, there has been a large interest in developing drugs affecting the α7 nAChRs for schizophrenia. In the present study we investigated, in rats, the effects of a selective α7 agonist (PNU282987) and a α7 positive allosteric modulator (PAM; NS1738) alone and in combination with the atypical antipsychotic drug risperidone for their utility as adjunct treatment in schizophrenia. Moreover we also investigated their utility as adjunct treatment in depression in combination with the SSRI citalopram. We found that NS1738 and to some extent also PNU282987, potentiated a subeffective dose of risperidone in the conditioned avoidance response test. Both drugs also potentiated the effect of a sub-effective concentration of risperidone on NMDA-induced currents in pyramidal cells of the medial prefrontal cortex. Moreover, NS1738 and PNU282987 enhanced recognition memory in the novel object recognition test, when given separately. Both drugs also potentiated accumbal but not prefrontal risperidone-induced dopamine release. Finally, PNU282987 reduced immobility in the forced swim test, indicating an antidepressant-like effect. Taken together, our data support the utility of drugs targeting the α7 nAChRs, perhaps especially α7 PAMs, to potentiate the effect of atypical antipsychotic drugs. Moreover, our data suggest that α7 agonists and PAMs can be used to ameliorate cognitive symptoms in schizophrenia and depression. PMID:27474687

  18. Basic OSF/Motif programming and applications

    SciTech Connect

    Brooks, D. ); Novak, B. )

    1992-09-15

    When users refer to Motif, they are usually talking about mwm, the window manager. However, when programmers mention Motif they are usually discussing the programming toolkit. This toolkit is used to develop new or modify existing applications. In this presentation, the term Motif will refer to the toolkit. Motif comes with a number of features that help users effectively use the applications built with it. The term look and feel may be overused; nonetheless, a consistent and well designed look and feel assists the user in Teaming and using new applications. The term point and click generally refers to using a mouse to select program commands. While Motif supports point and click, the toolkit also supports using the keyboard as a substitute for many operations. This gives a good typist a distinct advantage when using a familiar application. We will give an overview of the toolkit, touching on the user interface features and general programming considerations. Since the source code for many useful Motif programs is readily available, we will explain how to get these sources and touch on derived benefits. We win also point to other sources of on-line help and documentation. Finally, we will present some practical experiences developing applications.

  19. Detecting seeded motifs in DNA sequences.

    PubMed

    Pizzi, Cinzia; Bortoluzzi, Stefania; Bisognin, Andrea; Coppe, Alessandro; Danieli, Gian Antonio

    2005-01-01

    The problem of detecting DNA motifs with functional relevance in real biological sequences is difficult due to a number of biological, statistical and computational issues and also because of the lack of knowledge about the structure of searched patterns. Many algorithms are implemented in fully automated processes, which are often based upon a guess of input parameters from the user at the very first step. In this paper, we present a novel method for the detection of seeded DNA motifs, composed by regions with a different extent of variability. The method is based on a multi-step approach, which was implemented in a motif searching web tool (MOST). Overrepresented exact patterns are extracted from input sequences and clustered to produce motifs core regions, which are then extended and scored to generate seeded motifs. The combination of automated pattern discovery algorithms and different display tools for the evaluation and selection of results at several analysis steps can potentially lead to much more meaningful results than complete automation can produce. Experimental results on different yeast and human real datasets proved the methodology to be a promising solution for finding seeded motifs. MOST web tool is freely available at http://telethon.bio.unipd.it/bioinfo/MOST. PMID:16141193

  20. Detecting seeded motifs in DNA sequences

    PubMed Central

    Pizzi, Cinzia; Bortoluzzi, Stefania; Bisognin, Andrea; Coppe, Alessandro; Danieli, Gian Antonio

    2005-01-01

    The problem of detecting DNA motifs with functional relevance in real biological sequences is difficult due to a number of biological, statistical and computational issues and also because of the lack of knowledge about the structure of searched patterns. Many algorithms are implemented in fully automated processes, which are often based upon a guess of input parameters from the user at the very first step. In this paper, we present a novel method for the detection of seeded DNA motifs, composed by regions with a different extent of variability. The method is based on a multi-step approach, which was implemented in a motif searching web tool (MOST). Overrepresented exact patterns are extracted from input sequences and clustered to produce motifs core regions, which are then extended and scored to generate seeded motifs. The combination of automated pattern discovery algorithms and different display tools for the evaluation and selection of results at several analysis steps can potentially lead to much more meaningful results than complete automation can produce. Experimental results on different yeast and human real datasets proved the methodology to be a promising solution for finding seeded motifs. MOST web tool is freely available at . PMID:16141193

  1. Effects of the TLR2 Agonists MALP-2 and Pam3Cys in Isolated Mouse Lungs

    PubMed Central

    Barrenschee, Martina; Lex, Dennis; Uhlig, Stefan

    2010-01-01

    Background Gram-positive and Gram-negative bacteria are main causes of pneumonia or acute lung injury. They are recognized by the innate immune system via toll-like receptor-2 (TLR2) or TLR4, respectively. Among all organs, the lungs have the highest expression of TLR2 receptors, but little is known about the pulmonary consequences of their activation. Here we studied the effects of the TLR2/6 agonist MALP-2, the TLR2/1 agonist Pam3Cys and the TLR4 agonist lipopolysaccharide (LPS) on pro-inflammatory responses in isolated lungs. Methodology/Principal Findings Isolated perfused mouse lungs were perfused for 60 min or 180 min with MALP-2 (25 ng/mL), Pam3Cys (160 ng/mL) or LPS (1 µg/mL). We studied mediator release by enzyme linked immunosorbent assay (ELISA), the activation of mitogen activated protein kinase (MAPK) and AKT/protein kinase B by immunoblotting, and gene induction by quantitative polymerase chain reaction. All agonists activated the MAPK ERK1/2 and p38, but neither JNK or AKT kinase. The TLR ligands upregulated the inflammation related genes Tnf, Il1β, Il6, Il10, Il12, Ifng, Cxcl2 (MIP-2α) and Ptgs2. MALP-2 was more potent than Pam3Cys in inducing Slpi, Cxcl10 (IP10) and Parg. Remarkable was the strong induction of Tnc by MALP2, which was not seen with Pam3Cys or LPS. The growth factor related genes Areg and Hbegf were not affected. In addition, all three TLR agonists stimulated the release of IL-6, TNF, CXCL2 and CXCL10 protein from the lungs. Conclusions/Significance TLR2 and TLR4 activation leads to similar reactions in the lungs regarding MAPK activation, gene induction and mediator release. Several genes studied here have not yet been appreciated as targets of TLR2-activation in the lungs before, i.e., Slpi, tenascin C, Parg and Traf1. In addition, the MALP-2 dependent induction of Tnc may indicate the existence of TLR2/6-specific pathways. PMID:21124967

  2. Microbursts in JAWS depicted by Doppler radars, PAM, and aerial photographs

    NASA Technical Reports Server (NTRS)

    Fujita, T. T.; Wakimoto, R. M.

    1983-01-01

    Preliminary results obtained from the JAWS (Joint Airport Weather Studies) Project near Denver, Colorado in the spring and summer of 1982 using Doppler radar, PAM, and aerial photography are presented. The definitions of the microburst phenomenon are discussed, and statistics comparing NIMROD (Northern Illinois Meteorological Research On Downbursts) for the Midwest region are compared with JAWS for the High Plains region. Possible parent clouds of the microburst are considered, and an analysis of a macroburst/microburst event on July 14, 1982 is presented.

  3. The Arabidopsis thylakoid protein PAM68 is required for efficient D1 biogenesis and photosystem II assembly.

    PubMed

    Armbruster, Ute; Zühlke, Jessica; Rengstl, Birgit; Kreller, Renate; Makarenko, Elina; Rühle, Thilo; Schünemann, Danja; Jahns, Peter; Weisshaar, Bernd; Nickelsen, Jörg; Leister, Dario

    2010-10-01

    Photosystem II (PSII) is a multiprotein complex that functions as a light-driven water:plastoquinone oxidoreductase in photosynthesis. Assembly of PSII proceeds through a number of distinct intermediate states and requires auxiliary proteins. The photosynthesis affected mutant 68 (pam68) of Arabidopsis thaliana displays drastically altered chlorophyll fluorescence and abnormally low levels of the PSII core subunits D1, D2, CP43, and CP47. We show that these phenotypes result from a specific decrease in the stability and maturation of D1. This is associated with a marked increase in the synthesis of RC (the PSII reaction center-like assembly complex) at the expense of PSII dimers and supercomplexes. PAM68 is a conserved integral membrane protein found in cyanobacterial and eukaryotic thylakoids and interacts in split-ubiquitin assays with several PSII core proteins and known PSII assembly factors. Biochemical analyses of thylakoids from Arabidopsis and Synechocystis sp PCC 6803 suggest that, during PSII assembly, PAM68 proteins associate with an early intermediate complex that might contain D1 and the assembly factor LPA1. Inactivation of cyanobacterial PAM68 destabilizes RC but does not affect larger PSII assembly complexes. Our data imply that PAM68 proteins promote early steps in PSII biogenesis in cyanobacteria and plants, but their inactivation is differently compensated for in the two classes of organisms. PMID:20923938

  4. Comparison of the efficacy of HI6 and 2-PAM against soman, tabun, sarin, and VX in the rabbit

    SciTech Connect

    Koplovitz, I.; Stewart, J.R.

    1994-12-31

    This study compared the efficacy of H16 and 2-PAM against nerve agent (soman tabun sarin and VX) -induced lethality in the atropinesterase-free rabbits pretreated with vehicle (controls) or pyridostigmine. Treatment was administered at signs or 2 min after agent challenge and consisted ofoxime (l00umol/lkg) + atropine 13 mg(kg) (alone or together with diazepam). Twenty-four-h LD50 values were calculated for soman- and tabun-intoxicated animals, whereas 24-h survival was noted in animals given 10 LD50s of sarin or VX. In pyridostigmine and control rabbits intoxicated with soman and treated with oxime + atropine (alone or together with diazepam), HI6 was 35 times more effective than 2-PAM. In contrast 1116 was less effective than 2-PAM against tabun poisoning. In pyridostigmine-pretreated animals exposed to tabun, efficacy was increased more than 3-fold when compare to tabun-challenged animals treated with atropine + H16 alone. Both oximes were highly effective against satin and VX. These findings suggest that Hifi could replace 2-PAM as therapy for nerve agent poisoning because it is superior to 2-PAM against soman, and when used in pyridostigmine-pretreated animals it affords excellent protection against all four nerve agents when used in combination with atropine (alone or together with diazepam) therapy.

  5. 43 CFR 420.3 - Adjacent lands.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 43 Public Lands: Interior 1 2014-10-01 2014-10-01 false Adjacent lands. 420.3 Section 420.3 Public Lands: Interior Regulations Relating to Public Lands BUREAU OF RECLAMATION, DEPARTMENT OF THE INTERIOR...-managing agencies on adjacent lands (both public and private)....

  6. 43 CFR 420.3 - Adjacent lands.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 1 2013-10-01 2013-10-01 false Adjacent lands. 420.3 Section 420.3 Public Lands: Interior Regulations Relating to Public Lands BUREAU OF RECLAMATION, DEPARTMENT OF THE INTERIOR...-managing agencies on adjacent lands (both public and private)....

  7. 43 CFR 420.3 - Adjacent lands.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 43 Public Lands: Interior 1 2011-10-01 2011-10-01 false Adjacent lands. 420.3 Section 420.3 Public Lands: Interior Regulations Relating to Public Lands BUREAU OF RECLAMATION, DEPARTMENT OF THE INTERIOR OFF-ROAD VEHICLE USE § 420.3 Adjacent lands. When administratively feasible, the regulation of off-road vehicle use on Reclamation lands will...

  8. 43 CFR 420.3 - Adjacent lands.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 43 Public Lands: Interior 1 2012-10-01 2011-10-01 true Adjacent lands. 420.3 Section 420.3 Public Lands: Interior Regulations Relating to Public Lands BUREAU OF RECLAMATION, DEPARTMENT OF THE INTERIOR...-managing agencies on adjacent lands (both public and private)....

  9. 43 CFR 420.3 - Adjacent lands.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Adjacent lands. 420.3 Section 420.3 Public Lands: Interior Regulations Relating to Public Lands BUREAU OF RECLAMATION, DEPARTMENT OF THE INTERIOR OFF-ROAD VEHICLE USE § 420.3 Adjacent lands. When administratively feasible, the regulation of...

  10. Space-related pharma-motifs for fast search of protein binding motifs and polypharmacological targets

    PubMed Central

    2012-01-01

    Background To discover a compound inhibiting multiple proteins (i.e. polypharmacological targets) is a new paradigm for the complex diseases (e.g. cancers and diabetes). In general, the polypharmacological proteins often share similar local binding environments and motifs. As the exponential growth of the number of protein structures, to find the similar structural binding motifs (pharma-motifs) is an emergency task for drug discovery (e.g. side effects and new uses for old drugs) and protein functions. Results We have developed a Space-Related Pharmamotifs (called SRPmotif) method to recognize the binding motifs by searching against protein structure database. SRPmotif is able to recognize conserved binding environments containing spatially discontinuous pharma-motifs which are often short conserved peptides with specific physico-chemical properties for protein functions. Among 356 pharma-motifs, 56.5% interacting residues are highly conserved. Experimental results indicate that 81.1% and 92.7% polypharmacological targets of each protein-ligand complex are annotated with same biological process (BP) and molecular function (MF) terms, respectively, based on Gene Ontology (GO). Our experimental results show that the identified pharma-motifs often consist of key residues in functional (active) sites and play the key roles for protein functions. The SRPmotif is available at http://gemdock.life.nctu.edu.tw/SRP/. Conclusions SRPmotif is able to identify similar pharma-interfaces and pharma-motifs sharing similar binding environments for polypharmacological targets by rapidly searching against the protein structure database. Pharma-motifs describe the conservations of binding environments for drug discovery and protein functions. Additionally, these pharma-motifs provide the clues for discovering new sequence-based motifs to predict protein functions from protein sequence databases. We believe that SRPmotif is useful for elucidating protein functions and drug discovery

  11. Extracting body image symptom dimensions among eating disorder patients: the Profile Analysis via Multidimensional Scaling (PAMS) approach.

    PubMed

    Olatunji, Bunmi O; Kim, Se-Kang; Wall, David

    2015-09-01

    The present study employs Profile Analysis via Multidimensional Scaling (PAMS), a procedure for extracting dimensions, in order to identify core eating disorder symptoms in a clinical sample. A large sample of patients with eating disorders (N=5193) presenting for treatment completed the Eating Disorders Inventory-2 (EDI-2; Garner, 1991), and PAMS was then employed to estimate individual profile weights that reflect the degree to which an individual's observed symptom profile approximates the pattern of the dimensions. The findings revealed three symptom dimensions: Body Thinness, Body Perfectionism, and Body Awareness. Subsequent analysis using individual level data illustrate that the PAMS profiles properly operate as prototypical profiles that encapsulate all individuals' response patterns. The implications of these dimensional findings for the assessment and diagnosis of eating disorders are discussed. PMID:25996520

  12. Experimental investigation of PAM, CAP and DMT modulations efficiency over a double-step-index polymer optical fiber

    NASA Astrophysics Data System (ADS)

    Stepniak, G.; Siuzdak, J.

    2014-08-01

    Investigated was the transmission over step index POF that is 50 m/100 m long with a red DVD laser as a source and a Si p-i-n commercial photo-detector. The maximum bit rates of three modulation formats: PAM, CAP and DMT were sought. Their constellation sizes and symbol rates were varied in order to maximize FEC limited throughputs for each modulation whereas the laser operating point and relevant optical powers were maintained constant for all the modulations. The maximum throughputs were similar for PAM and CAP, namely 3.3/2 Gbit/s for PAM, and 3.15/2.1 for CAP for 50/100 m fiber, respectively. The bit rates for DMT were 2.65/1.65 Gbit/s for the respective lengths of the fiber. We attribute the inferior performance of DMT to its high value of peak to average power ratio.

  13. Identification of PAM4 (clivatuzumab)-reactive epitope on MUC5AC: a promising biomarker and therapeutic target for pancreatic cancer.

    PubMed

    Liu, Donglin; Chang, Chien-Hsing; Gold, David V; Goldenberg, David M

    2015-02-28

    PAM4 is a monoclonal antibody showing high specificity for pancreatic ductal adenocarcinoma (PDAC). Humanized PAM4 labeled with 90Y in combination with low-dose gemcitabine has shown promising therapeutic activity, and is being evaluated in a phase III clinical trial. Prior efforts have suggested that PAM4 potentially reacts with MUC5AC, a secretory mucin expressed de novo in early pancreatic neoplasia and retained throughout disease progression. In present study, we provide further evidence validating MUC5AC as the PAM4 antigen, and locate PAM4-reactive epitope within the N-terminal cysteine-rich subdomain 2 (Cys2), thus differentiating PAM4 from most anti-MUC5AC antibodies known to-date. Specifically, we show (i) PAM4-antigen and MUC5AC were co-localized in multiple human cancer cell lines, including Capan-1, BxPC-3, and CFPAC-1; (ii) MUC5AC-specific siRNA prominently reduced the expression of both MUC5AC and PAM4-antigen in CFPAC-1 cells; (iii) PAM4 preferentially binds to the void-volume fractions from Sepharose-CL2B chromatography of Capan-1 culture supernatants, which were revealed by Western blot to display the ladder pattern characteristic of oligomeric MUC5AC; and (iv) the N-terminal Cys2 within several recombinant MUC5AC fragments is essential for binding to PAM4. These findings shed light on the mechanism of PAM4-based diagnosis and treatment for pancreatic cancer, and guide further exploration of its clinical utility. PMID:25595893

  14. Identification of PAM4 (clivatuzumab)-reactive epitope on MUC5AC: A promising biomarker and therapeutic target for pancreatic cancer

    PubMed Central

    Liu, Donglin; Chang, Chien-Hsing; Gold, David V.; Goldenberg, David M.

    2015-01-01

    PAM4 is a monoclonal antibody showing high specificity for pancreatic ductal adenocarcinoma (PDAC). Humanized PAM4 labeled with 90Y in combination with low-dose gemcitabine has shown promising therapeutic activity, and is being evaluated in a phase III clinical trial. Prior efforts have suggested that PAM4 potentially reacts with MUC5AC, a secretory mucin expressed de novo in early pancreatic neoplasia and retained throughout disease progression. In present study, we provide further evidence validating MUC5AC as the PAM4 antigen, and locate PAM4-reactive epitope within the N-terminal cysteine-rich subdomain 2 (Cys2), thus differentiating PAM4 from most anti-MUC5AC antibodies known to-date. Specifically, we show (i) PAM4-antigen and MUC5AC were co-localized in multiple human cancer cell lines, including Capan-1, BxPC-3, and CFPAC-1; (ii) MUC5AC-specific siRNA prominently reduced the expression of both MUC5AC and PAM4-antigen in CFPAC-1 cells; (iii) PAM4 preferentially binds to the void-volume fractions from Sepharose-CL2B chromatography of Capan-1 culture supernatants, which were revealed by Western blot to display the ladder pattern characteristic of oligomeric MUC5AC; and (iv) the N-terminal Cys2 within several recombinant MUC5AC fragments is essential for binding to PAM4. These findings shed light on the mechanism of PAM4-based diagnosis and treatment for pancreatic cancer, and guide further exploration of its clinical utility. PMID:25595893

  15. Light-sheet photoacoustic microscopy (LIS-PAM) with optical ultrasound detection

    NASA Astrophysics Data System (ADS)

    Nuster, Robert; Slezak, Paul; Paltauf, Guenther

    2016-03-01

    Photoacoustic (or optoacoustic) microscopy has great potential as a diagnostic tool in biomedical research. For in vivo imaging, an important requirement is to keep the measurement time as short as possible. In light-sheet photoacoustic microscopy (LIS-PAM) a cylindrical lens illuminates a thin section perpendicular to the sample surface with a short laser pulse and a projection of the excited acoustic wave pattern leaving the sample is recorded with a camera. From the recorded data, a B-scan photoacoustic image is obtained by applying a two-dimensional reconstruction algorithm, without requiring any mechanical scanning. Hence, LIS-PAM is capable of real-time B-scan imaging with acoustical resolution within the individual B-scans and optical out of plane resolution up to a depth limited by optical diffusion. A 3D image is composed of reconstructed B-scan images recorded while scanning the excitation line along the sample surface. Using a camera with 200 Hz frame rate a C-scan image (5x5 mm2 field of view) can be recorded in less than 5 seconds (without averaging). The achievable sensitivity and resolution of the optical phase contrast detection system were estimated theoretically with 0.34 kPa mm without averaging and 30 μm, respectively. A first experiment on a phantom that mimics tissue properties shows the applicability of this technique for in-vivo imaging.

  16. PAM-ASK optical logic gates in an optical fiber Sagnac interferometer

    NASA Astrophysics Data System (ADS)

    Ferreira, A. C.; Coêlho, A. G.; Sousa, J. R. R.; Sobrinho, C. S.; Magalhães, F. T. C. B.; Filho, A. F. G. F.; Guimarães, G. F.; Sales, J. C.; Menezes, J. W. M.; Sombra, A. S. B.

    2016-03-01

    In this work we performed a numerical study of optical logic gates based on a Sagnac interferometer, operating with short optical pulses (10 ps) in a PAM-ASK modulation scheme with binary amplitude modulation scheme. We examined the performance of a nonlinear Sagnac interferometer implementing two-input logical functions. We evaluated the effect resulting from an increment in the PAM coding parameter offset (ε) , considering the anomalous group velocity dispersion (GVD) and nonlinear self phase modulation (SPM) in a lossless configuration. By analysing the transmitted output, we conclude it is possible to obtain logic gates OR for two different power-splitting ratios ρ of the coupler (ρ = 0.1 and 0.2). After this step, we applied a dephasing control to the input pulses, aiming to achieve logic gates with ρ = 0.3 and ρ = 0.4 and to enhance the study of cases in which they had not been previously obtained. We obtained OR and AND logic gates with a phase variation study for ρ = 0.1 and 0.2. For ρ = 0.3 and 0.4, the variety and versatility of logic gates proved to be very broad where OR, AND and XOR gates were obtained.

  17. Characterisation of SOL density fluctuations in front of the LHCD PAM launcher in Tore

    SciTech Connect

    Oosako, T.; Ekedahl, A.; Goniche, M.; Achard, J.; Decker, J.; Peysson, Y.

    2011-12-23

    The density fluctuations, modified by Lower Hybrid Wave (LHW), is analyzed in Tore Supra with reference to the injected LHW power, density and the gap between LCFS (Last Closed Flux Surface) and the PAM (passive-active-multijunction) launcher. The density fluctuations are measured with RF probes installed at the PAM launcher front. A density scan at nominal toroidal field (3.8 T) shows that the fluctuations rate stays nearly constant ({approx}50%) for <3.5x10{sup 19}m{sup -3} and with LHW power up to 2MW. However, when increasing the density above <{approx}4.2x10{sup 19}m{sup -3}, using strong gas puffing, the fluctuation rate increases to >70% and is characterized by strong negative spikes, with typical frequency >100kHz. These are most likely originating from acceleration of electrons in the LHW near field due to parasitic absorption, as evidenced on the IR images, showing hot spots on the side limiters.

  18. Expression and modulation of nerve growth factor in murine keratinocytes (PAM 212)

    SciTech Connect

    Tron, V.A.; Coughlin, M.D.; Jang, D.E.; Stanisz, J.; Sauder, D.N. )

    1990-04-01

    Nerve growth factor (NGF) is a polypeptide that is required for normal development and maintenance of the sympathetic and sensory nervous systems. Skin has been shown to contain relatively high amounts of NGF, which is in keeping with the finding that the quantity of NGF in a tissue is proportional to the extent of sympathetic innervation of that organ. Since the keratinocyte, a major cellular constituent of the skin, is known to produce other growth factors and cytokines, our experiments were designed to determine whether keratinocytes are a source of NGF. Keratinocyte-conditioned media from the keratinocyte cell line PAM 212 contained NGF-like activity, approximately 2-3 ng/ml, as detected by the neurite outgrowth assay. Freshly isolated BALB/c keratinocytes contained approximately 0.1 ng/ml. Using a cDNA probe directed against NGF, we demonstrated the presence of a 1.3-kb NGF mRNA in both PAM 212 and BALB/c keratinocytes. Since ultraviolet radiation (UV) is a potentially important modulating factor for cytokines in skin, we examined the effect of UV on NGF mRNA expression. Although UV initially inhibited the expression of keratinocyte NGF mRNA (4 h), by 24 h an induction of NGF mRNA was seen. The NGF signal could also be induced by phorbol esters. Thus, keratinocytes synthesize and express NGF, and its expression is modulated by UVB and phorbol esters.

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

    PubMed

    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. PMID:26690911

  20. Using the Proactive Action Model (PAM) To Enhance Student Inquiry in Social Studies Education: From 1978 to the Dawn of the 21st Century.

    ERIC Educational Resources Information Center

    Peters, Richard

    The Proactive Action Model (PAM) is an approach to social studies education that involves students directly in research-type activities. Using the PAM technique, students may research a variety of social studies topics and follow a logical process of thought and inquiry towards a tangible product such as a report or presentation. This application…

  1. Mapping PAM4 (clivatuzumab), a monoclonal antibody in clinical trials for early detection and therapy of pancreatic ductal adenocarcinoma, to MUC5AC mucin

    PubMed Central

    2013-01-01

    Background PAM4, an antibody that has high specificity for pancreatic ductal adenocarcinoma (PDAC), compared to normal pancreas, benign lesions of the pancreas, and cancers originating from other tissues, is being investigated as a biomarker for early detection, as well as antibody-targeted imaging and therapy. Therefore, the identity of the antigen bound by this monoclonal antibody (MAb) can provide information leading to improved use of the antibody. Prior results suggested the antigen is a mucin-type glycoprotein rich in cysteine disulfide bridges that provide stable conformation for the PAM4-epitope. Methods Indirect and sandwich enzyme immunoassays (EIA) were performed to compare and contrast the reactivity of PAM4 with several anti-mucin antibodies having known reactivity to specific mucin species (e.g., MUC1, MUC4, MUC5AC, etc.). Studies designed to block reactivity of PAM4 with its specific antigen also were performed. Results We demonstrate that MAbs 2-11 M1 and 45 M1, each reactive with MUC5AC, are able to provide signal in a heterologous sandwich immunoassay where PAM4 is the capture antibody. Further, we identify MAbs 21 M1, 62 M1, and 463 M1, each reactive with MUC5AC, as inhibiting the reaction of PAM4 with its specific epitope. MAbs directed to MUC1, MUC3, MUC4, MUC16 and CEACAM6 are not reactive with PAM4-captured antigen, nor are they able to block the reaction of PAM4 with its antigen. Conclusions These data implicate MUC5AC as a specific mucin species to which PAM4 is reactive. Furthermore, this realization may allow for the improvement of the current PAM4 serum-based immunoassay for detection of early-stage PDAC by the application of anti-MUC5AC MAbs as probes in this sandwich EIA. PMID:24257318

  2. Editorial: Eutrophication and hypoxia and their impacts on the ecosystem of the Changjiang Estuary and adjacent coastal environment

    NASA Astrophysics Data System (ADS)

    Zhang, Jing; Xiao, Tian; Huang, Daji; Liu, Su Mei; Fang, Jianguang

    2016-02-01

    The Changjiang (Yangtze River) Estuary plays an important role in the land-ocean interactions of East Asia, particularly in regard to the fate of land-derived materials and their impact on marine ecosystems in the Northwest Pacific Ocean. The 12 papers included in this special issue describe results from the MEcoPAM Study, an IMBER-China project, which occurred in 2011-2015. This project used a multi-disciplinary approach to understand ecosystem function of the Changjiang Estuary in response to multiple stressors (i.e. combined external forcings). The results presented here show that human activities in the watersheds have greatly changed the flux and variation of dissolved and particulate materials from the river. Further interactions between the Changjiang Watersheds and the East China Sea can dramatically modify the pathways of biogeochemistry and food web dynamics of the estuary and adjacent coastal environment at seasonal and inter-annual scales.

  3. Concentric network symmetry grasps authors' styles in word adjacency networks

    NASA Astrophysics Data System (ADS)

    Amancio, Diego R.; Silva, Filipi N.; Costa, Luciano da F.

    2015-06-01

    Several characteristics of written texts have been inferred from statistical analysis derived from networked models. Even though many network measurements have been adapted to study textual properties at several levels of complexity, some textual aspects have been disregarded. In this paper, we study the symmetry of word adjacency networks, a well-known representation of text as a graph. A statistical analysis of the symmetry distribution performed in several novels showed that most of the words do not display symmetric patterns of connectivity. More specifically, the merged symmetry displayed a distribution similar to the ubiquitous power-law distribution. Our experiments also revealed that the studied metrics do not correlate with other traditional network measurements, such as the degree or the betweenness centrality. The discriminability power of the symmetry measurements was verified in the authorship attribution task. Interestingly, we found that specific authors prefer particular types of symmetric motifs. As a consequence, the authorship of books could be accurately identified in 82.5% of the cases, in a dataset comprising books written by 8 authors. Because the proposed measurements for text analysis are complementary to the traditional approach, they can be used to improve the characterization of text networks, which might be useful for applications based on stylistic classification.

  4. MEME Suite: tools for motif discovery and searching

    PubMed Central

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

    2009-01-01

    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. PMID:19458158

  5. Dynamic bending of bionic flexible body driven by pneumatic artificial muscles(PAMs) for spinning gait of quadruped robot

    NASA Astrophysics Data System (ADS)

    Lei, Jingtao; Yu, Huangying; Wang, Tianmiao

    2016-01-01

    The body of quadruped robot is generally developed with the rigid structure. The mobility of quadruped robot depends on the mechanical properties of the body mechanism. It is difficult for quadruped robot with rigid structure to achieve better mobility walking or running in the unstructured environment. A kind of bionic flexible body mechanism for quadruped robot is proposed, which is composed of one bionic spine and four pneumatic artificial muscles(PAMs). This kind of body imitates the four-legged creatures' kinematical structure and physical properties, which has the characteristic of changeable stiffness, lightweight, flexible and better bionics. The kinematics of body bending is derived, and the coordinated movement between the flexible body and legs is analyzed. The relationship between the body bending angle and the PAM length is obtained. The dynamics of the body bending is derived by the floating coordinate method and Lagrangian method, and the driving force of PAM is determined. The experiment of body bending is conducted, and the dynamic bending characteristic of bionic flexible body is evaluated. Experimental results show that the bending angle of the bionic flexible body can reach 18°. An innovation body mechanism for quadruped robot is proposed, which has the characteristic of flexibility and achieve bending by changing gas pressure of PAMs. The coordinated movement of the body and legs can achieve spinning gait in order to improve the mobility of quadruped robot.

  6. Evaluating the Invariance of Cognitive Profile Patterns Derived from Profile Analysis via Multidimensional Scaling (PAMS): A Bootstrapping Approach

    ERIC Educational Resources Information Center

    Kim, Se-Kang

    2010-01-01

    The aim of the current study is to validate the invariance of major profile patterns derived from multidimensional scaling (MDS) by bootstrapping. Profile Analysis via Multidimensional Scaling (PAMS) was employed to obtain profiles and bootstrapping was used to construct the sampling distributions of the profile coordinates and the empirical…

  7. Single channel 112Gbit/sec PAM4 at 56Gbaud with digital signal processing for data centers applications.

    PubMed

    Sadot, Dan; Dorman, G; Gorshtein, Albert; Sonkin, Eduard; Vidal, Or

    2015-01-26

    112Gbit/sec DSP-based single channel transmission of PAM4 at 56Gbaud over 15GHz of effective analog bandwidth is experimentally demonstrated. The DSP enables use of mature 25G optoelectronics for 2-10km datacenter intra-connections, and 8Tbit/sec over 80km interconnections between data centers. PMID:25835858

  8. Polarization-insensitive PAM-4-carrying free-space orbital angular momentum (OAM) communications.

    PubMed

    Liu, Jun; Wang, Jian

    2016-02-22

    We present a simple configuration incorporating single polarization-sensitive phase-only liquid crystal spatial light modulator (SLM) to facilitate polarization-insensitive free-space optical communications employing orbital angular momentum (OAM) modes. We experimentally demonstrate several polarization-insensitive optical communication subsystems by propagating a single OAM mode, multicasting 4 and 10 OAM modes, and multiplexing 8 OAM modes, respectively. Free-space polarization-insensitive optical communication links using OAM modes that carry four-level pulse-amplitude modulation (PAM-4) signal are demonstrated in the experiment. The observed optical signal-to-noise ratio (OSNR) penalties are less than 1 dB in both polarization-insensitive N-fold OAM modes multicasting and multiple OAM modes multiplexing at a bit-error rate (BER) of 2e-3 (enhanced forward-error correction (EFEC) threshold). PMID:26907073

  9. Iterative nonlinear ISI cancellation in optical tilted filter-based Nyquist 4-PAM system

    NASA Astrophysics Data System (ADS)

    Ju, Cheng; Liu, Na

    2016-09-01

    The conventional double sideband (DSB) modulation and direct detection scheme suffers from severer power fading, linear and nonlinear inter-symbol interference (ISI) caused by fiber dispersion and square-law direct detection. The system's frequency response deteriorates at high frequencies owing to the limited device bandwidth. Moreover, the linear and nonlinear ISI is enhanced induced by the bandwidth limited effect. In this paper, an optical tilted filter is used to mitigate the effect of power fading, and improve the high frequency response of bandwidth limited device in Nyquist 4-ary pulse amplitude modulation (4-PAM) system. Furtherly, iterative technique is introduced to mitigate the nonlinear ISI caused by the combined effects of electrical Nyquist filter, limited device bandwidth, optical tilted filter, dispersion, and square-law photo-detection. Thus, the system's frequency response is greatly improved and the delivery distance can be extended.

  10. New FEC encoding technique based parity selected codes for 4-ary PAM signal

    NASA Astrophysics Data System (ADS)

    Al-Qawasmi, Abdel-Rahman; Al-Lawama, Aiman

    2011-10-01

    To ensure reliable communications,(an algorithm has been built for bit error detection and correction). To achieve this goal, special codeword combinations and their related parity codes are used as powerful detection and correction codes. All codeword combinations are divided into four main groups, where each code in a group has a common parity code. In this paper, we used the distance feature between special selected codeword combinations and unique combinations from a fixed set to improve the BER in digital communications systems. The results of using such algorithm show that 100% correction of two errors and 66% of three errors. The probability of detection is very high and up to 8 errors in different positions. All correction and detection processes are achieved with minimum number of transmitted bits representing 4- ary PAM symbols with compression ratio equals to 76% comparing to traditional distance parity check codes.

  11. The Motif of Meeting in Digital Education

    ERIC Educational Resources Information Center

    Sheail, Philippa

    2015-01-01

    This article draws on theoretical work which considers the composition of meetings, in order to think about the form of the meeting in digital environments for higher education. To explore the motif of meeting, I undertake a "compositional interpretation" (Rose, 2012) of the default interface offered by "Collaborate", an…

  12. A survey of motif finding Web tools for detecting binding site motifs in ChIP-Seq data

    PubMed Central

    2014-01-01

    Abstract ChIP-Seq (chromatin immunoprecipitation sequencing) has provided the advantage for finding motifs as ChIP-Seq experiments narrow down the motif finding to binding site locations. Recent motif finding tools facilitate the motif detection by providing user-friendly Web interface. In this work, we reviewed nine motif finding Web tools that are capable for detecting binding site motifs in ChIP-Seq data. We showed each motif finding Web tool has its own advantages for detecting motifs that other tools may not discover. We recommended the users to use multiple motif finding Web tools that implement different algorithms for obtaining significant motifs, overlapping resemble motifs, and non-overlapping motifs. Finally, we provided our suggestions for future development of motif finding Web tool that better assists researchers for finding motifs in ChIP-Seq data. Reviewers This article was reviewed by Prof. Sandor Pongor, Dr. Yuriy Gusev, and Dr. Shyam Prabhakar (nominated by Prof. Limsoon Wong). PMID:24555784

  13. On the time-course of adjacent and non-adjacent transposed-letter priming

    PubMed Central

    Ktori, Maria; Kingma, Brechtsje; Hannagan, Thomas; Holcomb, Phillip J.; Grainger, Jonathan

    2014-01-01

    We compared effects of adjacent (e.g., atricle-ARTICLE) and non-adjacent (e.g., actirle-ARTICLE) transposed-letter (TL) primes in an ERP study using the sandwich priming technique. TL priming was measured relative to the standard double-substitution condition. We found significantly stronger priming effects for adjacent transpositions than non-adjacent transpositions (with 2 intervening letters) in behavioral responses (lexical decision latencies), and the adjacent priming effects emerged earlier in the ERP signal, at around 200 ms post-target onset. Non-adjacent priming effects emerged about 50 ms later and were short-lived, being significant only in the 250-300 ms time-window. Adjacent transpositions on the other hand continued to produce priming in the N400 time-window (300-500 ms post-target onset). This qualitatively different pattern of priming effects for adjacent and non-adjacent transpositions is discussed in the light of different accounts of letter transposition effects, and the utility of drawing a distinction between positional flexibility and positional noise. PMID:25364497

  14. The Molecular Evolution of the Qo Motif

    PubMed Central

    Kao, Wei-Chun; Hunte, Carola

    2014-01-01

    Quinol oxidation in the catalytic quinol oxidation site (Qo site) of cytochrome (cyt) bc1 complexes is the key step of the Q cycle mechanism, which laid the ground for Mitchell’s chemiosmotic theory of energy conversion. Bifurcated electron transfer upon quinol oxidation enables proton uptake and release on opposite membrane sides, thus generating a proton gradient that fuels ATP synthesis in cellular respiration and photosynthesis. The Qo site architecture formed by cyt b and Rieske iron–sulfur protein (ISP) impedes harmful bypass reactions. Catalytic importance is assigned to four residues of cyt b formerly described as PEWY motif in the context of mitochondrial complexes, which we now denominate Qo motif as comprehensive evolutionary sequence analysis of cyt b shows substantial natural variance of the motif with phylogenetically specific patterns. In particular, the Qo motif is identified as PEWY in mitochondria, α- and ε-Proteobacteria, Aquificae, Chlorobi, Cyanobacteria, and chloroplasts. PDWY is present in Gram-positive bacteria, Deinococcus–Thermus and haloarchaea, and PVWY in β- and γ-Proteobacteria. PPWF only exists in Archaea. Distinct patterns for acidophilic organisms indicate environment-specific adaptations. Importantly, the presence of PDWY and PEWY is correlated with the redox potential of Rieske ISP and quinone species. We propose that during evolution from low to high potential electron-transfer systems in the emerging oxygenic atmosphere, cyt bc1 complexes with PEWY as Qo motif prevailed to efficiently use high potential ubiquinone as substrate, whereas cyt b with PDWY operate best with low potential Rieske ISP and menaquinone, with the latter being the likely composition of the ancestral cyt bc1 complex. PMID:25115012

  15. DNA motif elucidation using belief propagation.

    PubMed

    Wong, Ka-Chun; Chan, Tak-Ming; Peng, Chengbin; Li, Yue; Zhang, Zhaolei

    2013-09-01

    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. PMID:23814189

  16. CombiMotif: A new algorithm for network motifs discovery in protein-protein interaction networks

    NASA Astrophysics Data System (ADS)

    Luo, Jiawei; Li, Guanghui; Song, Dan; Liang, Cheng

    2014-12-01

    Discovering motifs in protein-protein interaction networks is becoming a current major challenge in computational biology, since the distribution of the number of network motifs can reveal significant systemic differences among species. However, this task can be computationally expensive because of the involvement of graph isomorphic detection. In this paper, we present a new algorithm (CombiMotif) that incorporates combinatorial techniques to count non-induced occurrences of subgraph topologies in the form of trees. The efficiency of our algorithm is demonstrated by comparing the obtained results with the current state-of-the art subgraph counting algorithms. We also show major differences between unicellular and multicellular organisms. The datasets and source code of CombiMotif are freely available upon request.

  17. SOLIDS TRANSPORT BETWEEN ADJACENT CAFB FLUIDIZED BEDS

    EPA Science Inventory

    The report gives results of an experimental investigation of a pulsed, dense-phase pneumatic transport system for controlled circulation between adjacent fluidized beds. A model was developed to predict performance. The program provides technical support for EPA's program to demo...

  18. Border separation for adjacent orthogonal fields

    SciTech Connect

    Werner, B.L.; Khan, F.M.; Sharma, S.C.; Lee, C.K.; Kim, T.H. )

    1991-06-01

    Field border separations for adjacent orthogonal fields can be calculated geometrically, given the validity of some important assumptions such as beam alignment and field uniformity. Thermoluminescent dosimetry (TLD) measurements were used to investigate dose uniformity across field junctions as a function of field separation and, in particular, to review the CCSG recommendation for the treatment of medulloblastoma with separate head and spine fields.

  19. Discovery and SAR of a novel series of potent, CNS penetrant M4 PAMs based on a non-enolizable ketone core: Challenges in disposition.

    PubMed

    Wood, Michael R; Noetzel, Meredith J; Tarr, James C; Rodriguez, Alice L; Lamsal, Atin; Chang, Sichen; Foster, Jarrett J; Smith, Emery; Chase, Peter; Hodder, Peter S; Engers, Darren W; Niswender, Colleen M; Brandon, Nicholas J; Wood, Michael W; Duggan, Mark E; Conn, P Jeffrey; Bridges, Thomas M; Lindsley, Craig W

    2016-09-01

    This Letter describes the chemical optimization of a novel series of M4 PAMs based on a non-enolizable ketone core, identified from an MLPCN functional high-throughput screen. The HTS hit was potent, selective and CNS penetrant; however, the compound was highly cleared in vitro and in vivo. SAR provided analogs for which M4 PAM potency and CNS exposure were maintained; yet, clearance remained high. Metabolite identification studies demonstrated that this series was subject to rapid, and near quantitative, reductive metabolism to the corresponding secondary alcohol metabolite that was devoid of M4 PAM activity. PMID:27476142

  20. Use of synthetic peptides to locate novel integrin alpha2beta1-binding motifs in human collagen III.

    PubMed

    Raynal, Nicolas; Hamaia, Samir W; Siljander, Pia R-M; Maddox, Ben; Peachey, Anthony R; Fernandez, Rafael; Foley, Loraine J; Slatter, David A; Jarvis, Gavin E; Farndale, Richard W

    2006-02-17

    A set of 57 synthetic peptides encompassing the entire triplehelical domain of human collagen III was used to locate binding sites for the collagen-binding integrin alpha(2)beta(1). The capacity of the peptides to support Mg(2+)-dependent binding of several integrin preparations was examined. Wild-type integrins (recombinant alpha(2) I-domain, alpha(2)beta(1) purified from platelet membranes, and recombinant soluble alpha(2)beta(1) expressed as an alpha(2)-Fos/beta(1)-Jun heterodimer) bound well to only three peptides, two containing GXX'GER motifs (GROGER and GMOGER, where O is hydroxyproline) and one containing two adjacent GXX'GEN motifs (GLKGEN and GLOGEN). Two mutant alpha(2) I-domains were tested: the inactive T221A mutant, which recognized no peptides, and the constitutively active E318W mutant, which bound a larger subset of peptides. Adhesion of activated human platelets to GER-containing peptides was greater than that of resting platelets, and HT1080 cells bound well to more of the peptides compared with platelets. Binding of cells and recombinant proteins was abolished by anti-alpha(2) monoclonal antibody 6F1 and by chelation of Mg(2+). We describe two novel high affinity integrin-binding motifs in human collagen III (GROGER and GLOGEN) and a third motif (GLKGEN) that displays intermediate activity. Each motif was verified using shorter synthetic peptides. PMID:16326707

  1. Functional Motifs in Biochemical Reaction Networks

    PubMed Central

    Tyson, John J.; Novák, Béla

    2013-01-01

    The signal-response characteristics of a living cell are determined by complex networks of interacting genes, proteins, and metabolites. Understanding how cells respond to specific challenges, how these responses are contravened in diseased cells, and how to intervene pharmacologically in the decision-making processes of cells requires an accurate theory of the information-processing capabilities of macromolecular regulatory networks. Adopting an engineer’s approach to control systems, we ask whether realistic cellular control networks can be decomposed into simple regulatory motifs that carry out specific functions in a cell. We show that such functional motifs exist and review the experimental evidence that they control cellular responses as expected. PMID:20055671

  2. A Basic Set of Homeostatic Controller Motifs

    PubMed Central

    Drengstig, T.; Jolma, I.W.; Ni, X.Y.; Thorsen, K.; Xu, X.M.; Ruoff, P.

    2012-01-01

    Adaptation and homeostasis are essential properties of all living systems. However, our knowledge about the reaction kinetic mechanisms leading to robust homeostatic behavior in the presence of environmental perturbations is still poor. Here, we describe, and provide physiological examples of, a set of two-component controller motifs that show robust homeostasis. This basic set of controller motifs, which can be considered as complete, divides into two operational work modes, termed as inflow and outflow control. We show how controller combinations within a cell can integrate uptake and metabolization of a homeostatic controlled species and how pathways can be activated and lead to the formation of alternative products, as observed, for example, in the change of fermentation products by microorganisms when the supply of the carbon source is altered. The antagonistic character of hormonal control systems can be understood by a combination of inflow and outflow controllers. PMID:23199928

  3. Anticipated synchronization in neuronal network motifs

    NASA Astrophysics Data System (ADS)

    Matias, F. S.; Gollo, L. L.; Carelli, P. V.; Copelli, M.; Mirasso, C. R.

    2013-01-01

    Two identical dynamical systems coupled unidirectionally (in a so called master-slave configuration) exhibit anticipated synchronization (AS) if the one which receives the coupling (the slave) also receives a negative delayed self-feedback. In oscillatory neuronal systems AS is characterized by a phase-locking with negative time delay τ between the spikes of the master and of the slave (slave fires before the master), while in the usual delayed synchronization (DS) regime τ is positive (slave fires after the master). A 3-neuron motif in which the slave self-feedback is replaced by a feedback loop mediated by an interneuron can exhibits both AS and DS regimes. Here we show that AS is robust in the presence of noise in a 3 Hodgkin-Huxley type neuronal motif. We also show that AS is stable for large values of τ in a chain of connected slaves-interneurons.

  4. Motifs, modules and games in bacteria

    SciTech Connect

    Wolf, Denise M.; Arkin, Adam P.

    2003-04-01

    Global explorations of regulatory network dynamics, organization and evolution have become tractable thanks to high-throughput sequencing and molecular measurement of bacterial physiology. From these, a nascent conceptual framework is developing, that views the principles of regulation in term of motifs, modules and games. Motifs are small, repeated, and conserved biological units ranging from molecular domains to small reaction networks. They are arranged into functional modules, genetically dissectible cellular functions such as the cell cycle, or different stress responses. The dynamical functioning of modules defines the organism's strategy to survive in a game, pitting cell against cell, and cell against environment. Placing pathway structure and dynamics into an evolutionary context begins to allow discrimination between those physical and molecular features that particularize a species to its surroundings, and those that provide core physiological function. This approach promises to generate a higher level understanding of cellular design, pathway evolution and cellular bioengineering.

  5. Real-Time Secondary Aerosol Formation Measurements using a Photooxidation Reactor (PAM) and AMS in Urban Air and Biomass Smoke

    NASA Astrophysics Data System (ADS)

    Ortega, A. M.; Cubison, M.; Hayes, P. L.; Brune, W. H.; Hu, W.; Flynn, J. H.; Grossberg, N.; Lefer, B. L.; Alvarez, S. L.; Rappenglueck, B.; Bon, D.; Graus, M.; Warneke, C.; Gilman, J. B.; Kuster, W. C.; De Gouw, J. A.; Sullivan, A. P.; Jimenez, J. L.

    2011-12-01

    Recent field studies reveal large formation of secondary organic aerosol (SOA) under urban polluted ambient conditions, while SOA formation in biomass burning smoke appears to be variable but sometimes substantial. To study this formation in real-time, a Potential Aerosol Mass (PAM) photooxidation reactor was deployed with submicron aerosol size and chemical composition measurements during two studies: FLAME-3, a biomass-burning study at USDA Fire Sciences Laboratory in Missoula in 2009, MT and CalNex-LA in Pasadena, CA in 2010. A high-resolution aerosol mass spectrometer (HR-AMS) and a scanning mobility particle sizer (SMPS) alternated sampling unprocessed and PAM-processed aerosol. The PAM reactor produces OH concentrations up to 4 orders of magnitude higher than in ambient air, achieving equivalent aging of ~2 weeks in 5 minutes of processing. The OH intensity was also scanned every 20 min. in both field studies. Results show the value of PAM-AMS as a tool for in-situ evaluation of changes in OA concentration and composition due to SOA formation and POA oxidation. In FLAME-3, net SOA formation was variable among smokes from different biomasses; however, OA oxidation was always observed. The average SOA enhancement factor was 1.7 +/- 0.5 of the initial POA. Reactive VOCs such as toluene, monoterpenes, and acetaldehyde, as measured from a PIT-MS, decreased with increased PAM processing; however, formic acid, acetone, and some unidentified OVOCs increased after significant exposure to high oxidant levels suggesting multigenerational chemistry. Results from CalNex-LA show enhancement of SOA and inorganic aerosol from gas-phase precursors. This enhanced OA mass increase from PAM processing is maximum at night and correlates with trimethylbenzene concentrations, which indicates the dominance of short-lived SOA precursors in the LA Basin. A traditional SOA model with mostly aromatic precursors underpredicts the amount of SOA formed by about an order-of-magnitude, which

  6. Analyzing network reliability using structural motifs

    NASA Astrophysics Data System (ADS)

    Khorramzadeh, Yasamin; Youssef, Mina; Eubank, Stephen; Mowlaei, Shahir

    2015-04-01

    This paper uses the reliability polynomial, introduced by Moore and Shannon in 1956, to analyze the effect of network structure on diffusive dynamics such as the spread of infectious disease. We exhibit a representation for the reliability polynomial in terms of what we call structural motifs that is well suited for reasoning about the effect of a network's structural properties on diffusion across the network. We illustrate by deriving several general results relating graph structure to dynamical phenomena.

  7. Bioinformatics Approaches for Predicting Disordered Protein Motifs.

    PubMed

    Bhowmick, Pallab; Guharoy, Mainak; Tompa, Peter

    2015-01-01

    Short, linear motifs (SLiMs) in proteins are functional microdomains consisting of contiguous residue segments along the protein sequence, typically not more than 10 consecutive amino acids in length with less than 5 defined positions. Many positions are 'degenerate' thus offering flexibility in terms of the amino acid types allowed at those positions. Their short length and degenerate nature confers evolutionary plasticity meaning that SLiMs often evolve convergently. Further, SLiMs have a propensity to occur within intrinsically unstructured protein segments and this confers versatile functionality to unstructured regions of the proteome. SLiMs mediate multiple types of protein interactions based on domain-peptide recognition and guide functions including posttranslational modifications, subcellular localization of proteins, and ligand binding. SLiMs thus behave as modular interaction units that confer versatility to protein function and SLiM-mediated interactions are increasingly being recognized as therapeutic targets. In this chapter we start with a brief description about the properties of SLiMs and their interactions and then move on to discuss algorithms and tools including several web-based methods that enable the discovery of novel SLiMs (de novo motif discovery) as well as the prediction of novel occurrences of known SLiMs. Both individual amino acid sequences as well as sets of protein sequences can be scanned using these methods to obtain statistically overrepresented sequence patterns. Lists of putatively functional SLiMs are then assembled based on parameters such as evolutionary sequence conservation, disorder scores, structural data, gene ontology terms and other contextual information that helps to assess the functional credibility or significance of these motifs. These bioinformatics methods should certainly guide experiments aimed at motif discovery. PMID:26387106

  8. [Conserved motifs in voltage sensing proteins].

    PubMed

    Wang, Chang-He; Xie, Zhen-Li; Lv, Jian-Wei; Yu, Zhi-Dan; Shao, Shu-Li

    2012-08-25

    This paper was aimed to study conserved motifs of voltage sensing proteins (VSPs) and establish a voltage sensing model. All VSPs were collected from the Uniprot database using a comprehensive keyword search followed by manual curation, and the results indicated that there are only two types of known VSPs, voltage gated ion channels and voltage dependent phosphatases. All the VSPs have a common domain of four helical transmembrane segments (TMS, S1-S4), which constitute the voltage sensing module of the VSPs. The S1 segment was shown to be responsible for membrane targeting and insertion of these proteins, while S2-S4 segments, which can sense membrane potential, for protein properties. Conserved motifs/residues and their functional significance of each TMS were identified using profile-to-profile sequence alignments. Conserved motifs in these four segments are strikingly similar for all VSPs, especially, the conserved motif [RK]-X(2)-R-X(2)-R-X(2)-[RK] was presented in all the S4 segments, with positively charged arginine (R) alternating with two hydrophobic or uncharged residues. Movement of these arginines across the membrane electric field is the core mechanism by which the VSPs detect changes in membrane potential. The negatively charged aspartate (D) in the S3 segment is universally conserved in all the VSPs, suggesting that the aspartate residue may be involved in voltage sensing properties of VSPs as well as the electrostatic interactions with the positively charged residues in the S4 segment, which may enhance the thermodynamic stability of the S4 segments in plasma membrane. PMID:22907298

  9. Dynamic motifs in socio-economic networks

    NASA Astrophysics Data System (ADS)

    Zhang, Xin; Shao, Shuai; Stanley, H. Eugene; Havlin, Shlomo

    2014-12-01

    Socio-economic networks are of central importance in economic life. We develop a method of identifying and studying motifs in socio-economic networks by focusing on “dynamic motifs,” i.e., evolutionary connection patterns that, because of “node acquaintances” in the network, occur much more frequently than random patterns. We examine two evolving bi-partite networks: i) the world-wide commercial ship chartering market and ii) the ship build-to-order market. We find similar dynamic motifs in both bipartite networks, even though they describe different economic activities. We also find that “influence” and “persistence” are strong factors in the interaction behavior of organizations. When two companies are doing business with the same customer, it is highly probable that another customer who currently only has business relationship with one of these two companies, will become customer of the second in the future. This is the effect of influence. Persistence means that companies with close business ties to customers tend to maintain their relationships over a long period of time.

  10. Rab geranylgeranyl transferase catalyzes the geranylgeranylation of adjacent cysteines in the small GTPases Rab1A, Rab3A, and Rab5A.

    PubMed Central

    Farnsworth, C C; Seabra, M C; Ericsson, L H; Gelb, M H; Glomset, J A

    1994-01-01

    Rab proteins are Ras-related small GTPases that are geranylgeranylated on cysteine residues located at or near their C termini. They differ from other geranylgeranylated small GTPases in several important respects. (i) Most Rab proteins contain two adjacent cysteine residues within one of the following C-terminal sequence motifs: -XXCC, -XCXC, or -CCXX; (ii) a Rab protein that ends in a -XCXC motif has been shown to be geranylgeranylated on both adjacent cysteine residues; and (iii) Rab proteins are substrates of a unique Rab-specific geranylgeranyltransferase. Whether this enzyme catalyzes the geranylgeranylation of both cysteines is unknown. We addressed this question by direct structural analysis of in vitro prenylated proteins. We incubated recombinant Rab geranylgeranyltransferase, Rab escort protein, and [1-3H]geranylgeranyl pyrophosphate with recombinant wild-type Rab1A (-XXCC), Rab3A (-XCXC), or Rab5A (-CCXX) and treated each labeled protein with trypsin. We then analyzed the resulting peptides by HPLC and electrospray mass spectrometry and found that for each protein both C-terminal adjacent cysteines were geranylgeranylated. These results indicate that Rab geranylgeranyltransferase/Rab escort protein catalyzes the geranylgeranylation of both cysteines in Rab proteins with three distinct C-terminal motifs and suggest that other Rab proteins with these motifs may be similarly modified. PMID:7991565

  11. Rab geranylgeranyl transferase catalyzes the geranylgeranylation of adjacent cysteines in the small GTPases Rab1A, Rab3A, and Rab5A.

    PubMed

    Farnsworth, C C; Seabra, M C; Ericsson, L H; Gelb, M H; Glomset, J A

    1994-12-01

    Rab proteins are Ras-related small GTPases that are geranylgeranylated on cysteine residues located at or near their C termini. They differ from other geranylgeranylated small GTPases in several important respects. (i) Most Rab proteins contain two adjacent cysteine residues within one of the following C-terminal sequence motifs: -XXCC, -XCXC, or -CCXX; (ii) a Rab protein that ends in a -XCXC motif has been shown to be geranylgeranylated on both adjacent cysteine residues; and (iii) Rab proteins are substrates of a unique Rab-specific geranylgeranyltransferase. Whether this enzyme catalyzes the geranylgeranylation of both cysteines is unknown. We addressed this question by direct structural analysis of in vitro prenylated proteins. We incubated recombinant Rab geranylgeranyltransferase, Rab escort protein, and [1-3H]geranylgeranyl pyrophosphate with recombinant wild-type Rab1A (-XXCC), Rab3A (-XCXC), or Rab5A (-CCXX) and treated each labeled protein with trypsin. We then analyzed the resulting peptides by HPLC and electrospray mass spectrometry and found that for each protein both C-terminal adjacent cysteines were geranylgeranylated. These results indicate that Rab geranylgeranyltransferase/Rab escort protein catalyzes the geranylgeranylation of both cysteines in Rab proteins with three distinct C-terminal motifs and suggest that other Rab proteins with these motifs may be similarly modified. PMID:7991565

  12. Occurrence probability of structured motifs in random sequences.

    PubMed

    Robin, S; Daudin, J-J; Richard, H; Sagot, M-F; Schbath, S

    2002-01-01

    The problem of extracting from a set of nucleic acid sequences motifs which may have biological function is more and more important. In this paper, we are interested in particular motifs that may be implicated in the transcription process. These motifs, called structured motifs, are composed of two ordered parts separated by a variable distance and allowing for substitutions. In order to assess their statistical significance, we propose approximations of the probability of occurrences of such a structured motif in a given sequence. An application of our method to evaluate candidate promoters in E. coli and B. subtilis is presented. Simulations show the goodness of the approximations. PMID:12614545

  13. ET-Motif: Solving the Exact (l, d)-Planted Motif Problem Using Error Tree Structure.

    PubMed

    Al-Okaily, Anas; Huang, Chun-Hsi

    2016-07-01

    Motif finding is an important and a challenging problem in many biological applications such as discovering promoters, enhancers, locus control regions, transcription factors, and more. The (l, d)-planted motif search, PMS, is one of several variations of the problem. In this problem, there are n given sequences over alphabets of size [Formula: see text], each of length m, and two given integers l and d. The problem is to find a motif m of length l, where in each sequence there is at least an l-mer at a Hamming distance of [Formula: see text] of m. In this article, we propose ET-Motif, an algorithm that can solve the PMS problem in [Formula: see text] time and [Formula: see text] space. The time bound can be further reduced by a factor of m with [Formula: see text] space. In case the suffix tree that is built for the input sequences is balanced, the problem can be solved in [Formula: see text] time and [Formula: see text] space. Similarly, the time bound can be reduced by a factor of m using [Formula: see text] space. Moreover, the variations of the problem, namely the edit distance PMS and edited PMS (Quorum), can be solved using ET-Motif with simple modifications but upper bands of space and time. For edit distance PMS, the time and space bounds will be increased by [Formula: see text], while for edited PMS the increase will be of [Formula: see text] in the time bound. PMID:27152692

  14. Development of a microalgal PAM test method for Cu(II) in waters: comparison of using spectrofluorometry.

    PubMed

    Peña-Vázquez, E; Pérez-Conde, C; Costas, E; Moreno-Bondi, M C

    2010-08-01

    Test methods are needed to monitor Cu concentrations in reservoirs and water supplies. Dictyosphaerium chlorelloides (Chlorophyta) cells were immobilized in a silicate sol-gel and the toxic effects of Cu(II) were examined using different techniques: fluorescence measurements (using a spectrofluorometer with an optic fiber coupled to a flow cell or a 96-well-plate reader) or by Pulse Amplitude Modulation (PAM) parameters using a portable instrument and the pulse saturation method. Fm' and qN were the most sensitive indicator parameters when performing Cu analysis in water. D. chlorelloides PAM biosensor presented a detection limit of 0.6 mg l(-1) for Cu(II), within the limits to establish if Cu concentrations exceeded regulatory levels. Moreover, a 1.9 mg Cu l(-1) (30 microM) resistant strain of the D. chlorelloides microalgae was produced in order to obtain more selectivity on the metal determination. PMID:20354900

  15. Flocculation properties of polyacrylamide grafted carboxymethyl guar gum (CMG-g-PAM) synthesised by conventional and microwave assisted method.

    PubMed

    Pal, Sagar; Ghorai, S; Dash, M K; Ghosh, S; Udayabhanu, G

    2011-09-15

    A novel polymeric flocculant based on polyacrylamide grafted carboxymethyl guar gum (CMG-g-PAM) has been synthesised by grafting polyacrylamide chains onto CMG backbone using conventional redox grafting and microwave assisted grafting methods. Under optimum grafting conditions, 82% and 96% grafting efficiencies have been observed in case of conventional and microwave assisted methods respectively. The optimum sample has been characterized using viscometry, spectroscopic analysis, elemental analysis, molecular weight and radius of gyration determination. The flocculation characteristics of grafted and ungrafted polysaccharides have been evaluated in kaolin suspension, municipal sewage wastewater and decolourization efficiency of a dye solution (methylene blue). It is evident from results that CMG-g-PAM synthesised by microwave assisted grafting method is showing best flocculation characteristics. PMID:21802849

  16. CLIMP: Clustering Motifs via Maximal Cliques with Parallel Computing Design

    PubMed Central

    Chen, Yong

    2016-01-01

    A set of conserved binding sites recognized by a transcription factor is called a motif, which can be found by many applications of comparative genomics for identifying over-represented segments. Moreover, when numerous putative motifs are predicted from a collection of genome-wide data, their similarity data can be represented as a large graph, where these motifs are connected to one another. However, an efficient clustering algorithm is desired for clustering the motifs that belong to the same groups and separating the motifs that belong to different groups, or even deleting an amount of spurious ones. In this work, a new motif clustering algorithm, CLIMP, is proposed by using maximal cliques and sped up by parallelizing its program. When a synthetic motif dataset from the database JASPAR, a set of putative motifs from a phylogenetic foot-printing dataset, and a set of putative motifs from a ChIP dataset are used to compare the performances of CLIMP and two other high-performance algorithms, the results demonstrate that CLIMP mostly outperforms the two algorithms on the three datasets for motif clustering, so that it can be a useful complement of the clustering procedures in some genome-wide motif prediction pipelines. CLIMP is available at http://sqzhang.cn/climp.html. PMID:27487245

  17. CLIMP: Clustering Motifs via Maximal Cliques with Parallel Computing Design.

    PubMed

    Zhang, Shaoqiang; Chen, Yong

    2016-01-01

    A set of conserved binding sites recognized by a transcription factor is called a motif, which can be found by many applications of comparative genomics for identifying over-represented segments. Moreover, when numerous putative motifs are predicted from a collection of genome-wide data, their similarity data can be represented as a large graph, where these motifs are connected to one another. However, an efficient clustering algorithm is desired for clustering the motifs that belong to the same groups and separating the motifs that belong to different groups, or even deleting an amount of spurious ones. In this work, a new motif clustering algorithm, CLIMP, is proposed by using maximal cliques and sped up by parallelizing its program. When a synthetic motif dataset from the database JASPAR, a set of putative motifs from a phylogenetic foot-printing dataset, and a set of putative motifs from a ChIP dataset are used to compare the performances of CLIMP and two other high-performance algorithms, the results demonstrate that CLIMP mostly outperforms the two algorithms on the three datasets for motif clustering, so that it can be a useful complement of the clustering procedures in some genome-wide motif prediction pipelines. CLIMP is available at http://sqzhang.cn/climp.html. PMID:27487245

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

    NASA Astrophysics Data System (ADS)

    Payne, Joshua L.

    2016-05-01

    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 revealed that all circuit motifs have more than one function, with the number of functions per motif ranging from 12 to nearly 30,000. This indicates that some motifs are more functionally versatile than others. However, the individual circuit genotypes that constitute each motif are less robust to mutation if they have many functions, hinting that functionally versatile motifs may be less robust to mutation than motifs with few functions. Here, I explore the relationship between versatility and robustness in circuit motifs, demonstrating that functionally versatile motifs are robust to mutation despite the inherent tradeoff between versatility and robustness at the level of an individual circuit genotype.

  19. New aspects in the phase behaviour of poly-N-isopropyl acrylamide: systematic temperature dependent shrinking of PNiPAM assemblies well beyond the LCST

    NASA Astrophysics Data System (ADS)

    Bischofberger, Irmgard; Trappe, Veronique

    2015-10-01

    We investigate the phase behaviour of aqueous dispersions of poly-N-isopropyl acrylamide (PNiPAM) microgels above their lower critical solution temperature (LCST) and find that beyond a well-defined concentration the systems exhibit a peculiar behaviour: the microgels assemble into space-spanning gels that shrink in time while maintaining the shape of the container in which they have been formed. Over a wide range of concentrations this shrinking behaviour is independent of PNiPAM concentration, but systematically depends on temperature in a temperature range significantly exceeding the LCST. The overall shrinking characteristics are consistent with those expected for scaffolds made of materials that exhibit thermal contraction. However, for the PNiPAM assemblies contraction is irreversible and can be as large as 90%. Such characteristics disclose complex interactions between fully collapsed PNiPAM and water well beyond the LCST, the origin of which has yet to be elucidated.

  20. New aspects in the phase behaviour of poly-N-isopropyl acrylamide: systematic temperature dependent shrinking of PNiPAM assemblies well beyond the LCST.

    PubMed

    Bischofberger, Irmgard; Trappe, Veronique

    2015-01-01

    We investigate the phase behaviour of aqueous dispersions of poly-N-isopropyl acrylamide (PNiPAM) microgels above their lower critical solution temperature (LCST) and find that beyond a well-defined concentration the systems exhibit a peculiar behaviour: the microgels assemble into space-spanning gels that shrink in time while maintaining the shape of the container in which they have been formed. Over a wide range of concentrations this shrinking behaviour is independent of PNiPAM concentration, but systematically depends on temperature in a temperature range significantly exceeding the LCST. The overall shrinking characteristics are consistent with those expected for scaffolds made of materials that exhibit thermal contraction. However, for the PNiPAM assemblies contraction is irreversible and can be as large as 90%. Such characteristics disclose complex interactions between fully collapsed PNiPAM and water well beyond the LCST, the origin of which has yet to be elucidated. PMID:26493499

  1. Localization of the gene encoding peptidylglycine [alpha]-amidating monooxygenase (PAM) to human chromosome 5q14-5q21

    SciTech Connect

    Ouafik, L.H.; Giraud, P.; Oliver, C. ); Mattei, M.G. ); Eipper, B.A.; Mains, R.E. )

    1993-11-01

    Peptidylglycine [alpha]-amidating monooxygenase (PAM; EC 1.14.17.3) is a multifunctional protein containing two enzymes that act sequentially to catalyze the [alpha]-amidation of neuroendocrine peptides. Southern blot analysis of human placental DNA demonstrated that PAM is encoded by a single gene. The chromosomal localization of the PAM gene was established using in situ hybridization. A 2.2-kb human PAM cDNA hybridized to human metaphase chromosomes revealed a significant clustering of silver grains over chromosome 5 bands q14-q21. The gene encoding another enzyme important in the post-translational processing of neuroendocrine precursors, prohormone convertase 1 (PC1), is localized in the same region (5q15-q21). 14 refs., 2 figs.

  2. New aspects in the phase behaviour of poly-N-isopropyl acrylamide: systematic temperature dependent shrinking of PNiPAM assemblies well beyond the LCST

    PubMed Central

    Bischofberger, Irmgard; Trappe, Veronique

    2015-01-01

    We investigate the phase behaviour of aqueous dispersions of poly-N-isopropyl acrylamide (PNiPAM) microgels above their lower critical solution temperature (LCST) and find that beyond a well-defined concentration the systems exhibit a peculiar behaviour: the microgels assemble into space-spanning gels that shrink in time while maintaining the shape of the container in which they have been formed. Over a wide range of concentrations this shrinking behaviour is independent of PNiPAM concentration, but systematically depends on temperature in a temperature range significantly exceeding the LCST. The overall shrinking characteristics are consistent with those expected for scaffolds made of materials that exhibit thermal contraction. However, for the PNiPAM assemblies contraction is irreversible and can be as large as 90%. Such characteristics disclose complex interactions between fully collapsed PNiPAM and water well beyond the LCST, the origin of which has yet to be elucidated. PMID:26493499

  3. Adjacent Segment Pathology after Lumbar Spinal Fusion.

    PubMed

    Lee, Jae Chul; Choi, Sung-Woo

    2015-10-01

    One of the major clinical issues encountered after lumbar spinal fusion is the development of adjacent segment pathology (ASP) caused by increased mechanical stress at adjacent segments, and resulting in various radiographic changes and clinical symptoms. This condition may require surgical intervention. The incidence of ASP varies with both the definition and methodology adopted in individual studies; various risk factors for this condition have been identified, although a significant controversy still exists regarding their significance. Motion-preserving devices have been developed, and some studies have shown their efficacy of preventing ASP. Surgeons should be aware of the risk factors of ASP when planning a surgery, and accordingly counsel their patients preoperatively. PMID:26435804

  4. A conserved heptamer motif for ribosomal RNA transcription termination in animal mitochondria.

    PubMed Central

    Valverde, J R; Marco, R; Garesse, R

    1994-01-01

    A search of sequence data bases for a tridecamer transcription termination signal, previously described in human mtDNA as being responsible for the accumulation of mitochondrial ribosomal RNAs (rRNAs) in excess over the rest of mitochondrial genes, has revealed that this termination signal occurs in equivalent positions in a wide variety of organisms from protozoa to mammals. Due to the compact organization of the mtDNA, the tridecamer motif usually appears as part of the 3' adjacent gene sequence. Because in phylogenetically widely separated organisms the mitochondrial genome has experienced many rearrangements, it is interesting that its occurrence near the 3' end of the large rRNA is independent of the adjacent gene. The tridecamer sequence has diverged in phylogenetically widely separated organisms. Nevertheless, a well-conserved heptamer--TGGCAGA, the mitochondrial rRNA termination box--can be defined. Although extending the experimental evidence of its role as a transcription termination signal in humans will be of great interest, its evolutionary conservation strongly suggests that mitochondrial rRNA transcription termination could be a widely conserved mechanism in animals. Furthermore, the conservation of a homologous tridecamer motif in one of the last 3' secondary loops of nonmitochondrial 23S-like rRNAs suggests that the role of the sequence has changed during mitochondrial evolution. PMID:7515499

  5. Characterization of the peptidylglycine α-amidating monooxygenase (PAM) from the venom ducts of neogastropods, Conus bullatus and Conus geographus

    PubMed Central

    Ul-Hasan, Sabah; Burgess, Daniel M.; Gajewiak, Joanna; Li, Qing; Hu, Hao; Yandell, Mark; Olivera, Baldomero M.; Bandyopadhyay, Pradip K.

    2014-01-01

    Cone snails, genus Conus, are predatory marine snails that use venom to capture their prey. This venom contains a diverse array of peptide toxins, known as conotoxins, which undergo a diverse set of posttranslational modifications. Amidating enzymes modify peptides and proteins containing a C-terminal glycine residue, resulting in loss of the glycine residue and amidation of the preceding residue. A significant fraction of peptides present in the venom of cone snails contain C-terminal amidated residues, which are important for optimizing biological activity. This study describes the characterization of the amidating enzyme, peptidylglycine α-amidating monooxygenase (PAM), present in the venom duct of cone snails, Conus bullatus and Conus geographus. PAM is known to carry out two functions, peptidyl α-hydroxylating monooxygenase (PHM) and peptidylamido-glycolate lyase (PAL). In some animals, such as Drosophila melanogaster, these two functions are present in separate polypeptides, working as individual enzymes. In other animals, such as mammals and in Aplysia californica, PAM activity resides in a single, bifunctional polypeptide. Using specific oligonucleotide primers and reverse transcription-polymerase chain reaction we have identified and cloned from the venom duct cDNA library, a cDNA with 49% homology to PAM from A. californica. We have determined that both the PHM and PAL activities are encoded in one mRNA polynucleotide in both C. bullatus and C. geographus. We have directly demonstrated enzymatic activity catalyzing the conversion of dansyl-YVG-COOH to dansyl-YV-NH2 in cloned cDNA expressed in Drosophila S2 cells. PMID:23994590

  6. Potential Aerosol Mass (PAM) flow reactor measurements of SOA formation in a Ponderosa Pine forest in the southern Rocky Mountains during BEACHON-RoMBAS

    NASA Astrophysics Data System (ADS)

    Palm, B. B.; Ortega, A. M.; Campuzano Jost, P.; Day, D. A.; Kaser, L.; Karl, T.; Jud, W.; Hansel, A.; Fry, J.; Brown, S. S.; Zarzana, K. J.; Dube, W. P.; Wagner, N.; Draper, D.; Brune, W. H.; Jimenez, J. L.

    2012-12-01

    A Potential Aerosol Mass (PAM) photooxidation flow reactor was used in combination with an Aerodyne High Resolution Time-of-Flight Aerosol Mass Spectrometer to characterize biogenic secondary organic aerosol (SOA) formation in a terpene-dominated forest during the July-August 2011 Bio-hydro-atmosphere interactions of Energy, Aerosols, Carbon, H2O, Organics & Nitrogen - Rocky Mountain Biogenic Aerosol Study (BEACHON-RoMBAS) field campaign at the U.S. Forest Service Manitou Forest Observatory, Colorado, as well as in corresponding laboratory experiments. In the PAM reactor, a chosen oxidant (OH, O3, or NO3) was generated and controlled over a range of values up to 10,000 times ambient levels. High oxidant concentrations accelerated the gas-phase, heterogeneous, and possibly aqueous oxidative aging of volatile organic compounds (VOCs), inorganic gases, and existing aerosol, which led to repartitioning into the aerosol phase. PAM oxidative processing represented from a few hours up to ~20 days of equivalent atmospheric aging during the ~3 minute reactor residence time. During BEACHON-RoMBAS, PAM photooxidation enhanced SOA at intermediate OH exposure (1-10 equivalent days) but resulted in net loss of OA at long OH exposure (10-20 equivalent days), demonstrating the competing effects of functionalization vs. fragmentation (and possibly photolysis) as aging increased. PAM oxidation also resulted in f44 vs. f43 and Van Krevelen diagram (H/C vs. O/C) slopes similar to ambient oxidation, suggesting the PAM reactor employs oxidation pathways similar to ambient air. Single precursor aerosol yields were measured using the PAM reactor in the laboratory as a function of organic aerosol concentration and reacted hydrocarbon amounts. When applying the laboratory PAM yields with complete consumption of the most abundant VOCs measured at the forest site (monoterpenes, sesquiterpenes, MBO, and toluene), a simple model underpredicted the amount of SOA formed in the PAM reactor in the

  7. Multi-Parametric Relationships between PAM Measurements and Carbon Incorporation, an In Situ Approach

    PubMed Central

    Napoléon, Camille; Claquin, Pascal

    2012-01-01

    Primary production (PP) in the English Channel was measured using 13C uptake and compared to the electron transport rate (ETR) measured using PAM (pulse amplitude modulated fluorometer). The relationship between carbon incorporation (Pobs) and ETR was not linear but logarithmic. This result can be explained by alternative electron sinks at high irradiance which protect the phytoplankton from photoinhibition. A multi-parametric model was developed to estimate PP by ETR. This approach highlighted the importance of taking physicochemical parameters like incident light and nutrient concentrations into account. The variation in the ETR/Pobs ratio as a function of the light revealed different trends which were characterized by three parameters (Rmax, the maximum value of ETR/Pobs; ERmax, the light intensity at which Rmax is measured; γ the initial slope of the curve). Based on the values of these three parameters, data were divided into six groups which were highly dependent on the seasons and on the physicochemical conditions. Using the multi-parametric model which we defined by Pobs and ETR measurements at low frequencies, the high frequency measurements of ETR enabled us to estimate the primary production capacity between November 2009 and December 2010 at high temporal and spatial scales. PMID:22911698

  8. Characterization of Four Bifunctional Plant IAM/PAM-Amidohydrolases Capable of Contributing to Auxin Biosynthesis

    PubMed Central

    Sánchez-Parra, Beatriz; Frerigmann, Henning; Pérez Alonso, Marta-Marina; Carrasco Loba, Víctor; Jost, Ricarda; Hentrich, Mathias; Pollmann, Stephan

    2014-01-01

    Amidases [EC 3.5.1.4] capable of converting indole-3-acetamide (IAM) into the major plant growth hormone indole-3-acetic acid (IAA) are assumed to be involved in auxin de novo biosynthesis. With the emerging amount of genomics data, it was possible to identify over forty proteins with substantial homology to the already characterized amidases from Arabidopsis and tobacco. The observed high conservation of amidase-like proteins throughout the plant kingdom may suggest an important role of theses enzymes in plant development. Here, we report cloning and functional analysis of four, thus far, uncharacterized plant amidases from Oryza sativa, Sorghum bicolor, Medicago truncatula, and Populus trichocarpa. Intriguingly, we were able to demonstrate that the examined amidases are also capable of converting phenyl-2-acetamide (PAM) into phenyl-2-acetic acid (PAA), an auxin endogenous to several plant species including Arabidopsis. Furthermore, we compared the subcellular localization of the enzymes to that of Arabidopsis AMI1, providing further evidence for similar enzymatic functions. Our results point to the presence of a presumably conserved pathway of auxin biosynthesis via IAM, as amidases, both of monocot, and dicot origins, were analyzed. PMID:27135507

  9. PAM: Particle automata model in simulation of Fusarium graminearum pathogen expansion.

    PubMed

    Wcisło, Rafał; Miller, S Shea; Dzwinel, Witold

    2016-01-21

    The multi-scale nature and inherent complexity of biological systems are a great challenge for computer modeling and classical modeling paradigms. We present a novel particle automata modeling metaphor in the context of developing a 3D model of Fusarium graminearum infection in wheat. The system consisting of the host plant and Fusarium pathogen cells can be represented by an ensemble of discrete particles defined by a set of attributes. The cells-particles can interact with each other mimicking mechanical resistance of the cell walls and cell coalescence. The particles can move, while some of their attributes can be changed according to prescribed rules. The rules can represent cellular scales of a complex system, while the integrated particle automata model (PAM) simulates its overall multi-scale behavior. We show that due to the ability of mimicking mechanical interactions of Fusarium tip cells with the host tissue, the model is able to simulate realistic penetration properties of the colonization process reproducing both vertical and lateral Fusarium invasion scenarios. The comparison of simulation results with micrographs from laboratory experiments shows encouraging qualitative agreement between the two. PMID:26549468

  10. Evaluation of different algal species sensitivity to mercury and metolachlor by PAM-fluorometry.

    PubMed

    Juneau, P; Dewez, D; Matsui, S; Kim, S G; Popovic, R

    2001-11-01

    In this study, the pulse-amplitude-modulation (PAM)-fluorometric method was used to evaluate the difference in the sensitivity to mercury (Hg) and metolachlor of six algal species: Ankistrodesmus falcatus, Selenastrum capricornutum, Chlorella vulgaris, Nannoplankton (PLS), Microcystis aeruginosa and Pediastrum biwae. We found that the fluorescence parameters (phiM, the maximal photosystem II (PSII) quantum yield, phi'M, the operational PSII quantum yield at steady state of electron transport, Q(P), the photochemical quenching value, and Q(N), the non-photochemical quenching value) were appropriate indicators for inhibitory effects of mercury but only phi'M and Q(N) were useful for metolachlor. The examined algal species showed very different levels of sensitivity to the effect of Hg and of metolachlor. The most sensitive species to Hg and metolachlor were respectively M. aeruginosa and A. falcatus, while the least sensitive were C. vulgaris and P. biwae. We interpreted these differences by the action mode of pollutants and by the different metabolism properties and morphological characteristics between algal species. These results related to fluorescence parameters may offer useful tool to be used in bioassay for different pollutants. Heterogeneous algal sensitivity to the same pollutant suggests the need to use a battery of species to evaluate the effects of mixtures of pollutants in aquatic systems. PMID:11680755

  11. Adjacent Segment Pathology after Anterior Cervical Fusion

    PubMed Central

    Chung, Jae Yoon; Park, Jong-Beom; Seo, Hyoung-Yeon

    2016-01-01

    Anterior cervical fusion has become a standard of care for numerous pathologic conditions of the cervical spine. However, subsequent development of clinically significant disc disease at levels adjacent to fused discs is a serious long-term complication of this procedure. As more patients live longer after surgery, it is foreseeable that adjacent segment pathology (ASP) will develop in increasing numbers of patients. Also, ASP has been studied more intensively with the recent popularity of motion preservation technologies like total disc arthroplasty. The true nature and scope of ASP remains poorly understood. The etiology of ASP is most likely multifactorial. Various factors including altered biomechanical stresses, surgical disruption of soft tissue and the natural history of cervical disc disease contribute to the development of ASP. General factors associated with disc degeneration including gender, age, smoking and sports may play a role in the development of ASP. Postoperative sagittal alignment and type of surgery are also considered potential causes of ASP. Therefore, a spine surgeon must be particularly careful to avoid unnecessary disruption of the musculoligamentous structures, reduced risk of direct injury to the disc during dissection and maintain a safe margin between the plate edge and adjacent vertebrae during anterior cervical fusion. PMID:27340541

  12. Adjacent Segment Pathology after Anterior Cervical Fusion.

    PubMed

    Chung, Jae Yoon; Park, Jong-Beom; Seo, Hyoung-Yeon; Kim, Sung Kyu

    2016-06-01

    Anterior cervical fusion has become a standard of care for numerous pathologic conditions of the cervical spine. However, subsequent development of clinically significant disc disease at levels adjacent to fused discs is a serious long-term complication of this procedure. As more patients live longer after surgery, it is foreseeable that adjacent segment pathology (ASP) will develop in increasing numbers of patients. Also, ASP has been studied more intensively with the recent popularity of motion preservation technologies like total disc arthroplasty. The true nature and scope of ASP remains poorly understood. The etiology of ASP is most likely multifactorial. Various factors including altered biomechanical stresses, surgical disruption of soft tissue and the natural history of cervical disc disease contribute to the development of ASP. General factors associated with disc degeneration including gender, age, smoking and sports may play a role in the development of ASP. Postoperative sagittal alignment and type of surgery are also considered potential causes of ASP. Therefore, a spine surgeon must be particularly careful to avoid unnecessary disruption of the musculoligamentous structures, reduced risk of direct injury to the disc during dissection and maintain a safe margin between the plate edge and adjacent vertebrae during anterior cervical fusion. PMID:27340541

  13. Blood-brain barrier penetration of novel pyridinealdoxime methiodide (PAM)-type oximes examined by brain microdialysis with LC-MS/MS

    SciTech Connect

    Okuno, Sou; Sakurada, Koichi Ohta, Hikoto; Ikegaya, Hiroshi; Kazui, Yuko; Akutsu, Tomoko; Takatori, Takehiko; Iwadate, Kimiharu

    2008-02-15

    To develop a new reactivator of inhibited acetylcholinesterase (AChE) that can easily penetrate the blood-brain barrier (BBB), BBB penetration of 6 known and novel pyridinealdoxime methiodide (PAM)-type oximes (alkylPAMs) with relatively high reactivation activities was examined by in vivo rat brain microdialysis with liquid chromatography-mass spectrometry (LC-MS/MS). The 50% lethal dose (LD{sub 50}) of alkylPAMs was intravenously determined for Wistar rats, then the limit of detection, quantification range and linearity of the calibration curve of the alkylPAMs in dialysate and blood were determined by LC-MS/MS. Following 10% LD{sub 50} intravenous administration of the alkylPAMs, 4-[(hydroxyimino) methyl]-1-(2-phenylethyl) pyridinium bromide (4-PAPE) and 4-[(hydroxyimino) methyl]-1-octylpyridinium bromide (4-PAO) appeared in the dialysate. Striatal extracellular fluid/blood concentration ratios were 0.039 {+-} 0.018 and 0.301 {+-} 0.183 (mean {+-} SEM), respectively, 1 h after treatment. This is the first report of BBB penetration of 4-PAPE, and the concentration ratio was smaller than that of 2-PAM.The mean BBB penetration of 4-PAO was approximately 30%, indicating that intravenous administration of 4-PAO may be effective for the reactivation of blocked cholinesterase in the brain. However, the toxicity of 4-PAO (LD{sub 50}; 8.89 mg/kg) was greater than that of 2-PAM. Further investigation is required to determine the effects of these alkylPAMs in organophosphate poisoning.

  14. Luminescent and magnetic Fe3O4/Py/PAM nanocomposites for the chromium(VI) determination.

    PubMed

    Hong, Shi; Chen, Hongqi; Wang, Leyu; Wang, Lun

    2008-07-01

    A novel luminescent and magnetic Fe(3)O(4)/pyrene/polyacrylamide (Fe(3)O(4)/Py/PAM) nanocomposite has been prepared under ultrasonic radiation. This magnetic nanocomposite combined with pyrene would lead to a special functional magnetic luminescent composite that enjoys both the advantages of magnetic nanoparticles of Fe(3)O(4) and fluorescence nanoparticles of pyrene. Taking advantage of the magnetic property of Fe(3)O(4) nanocomposites, we can separate Fe(3)O(4)/Py/PAM nanocomposites from solution easily just by using a permanent magnet. Based on the fluorescence quenching of Fe(3)O(4)/Py/PAM nanocomposites by Cr(VI), a method for the selective determination of Cr(VI), without separation of Cr(III) in water, was developed. Under optimal experimental conditions, a limit of detection of 0.01 microg mL(-1) was achieved. The calibration curve was linear over the concentration range of 0.1-14.0 microg mL(-1) with a correlation coefficient of 0.9975. The proposed method has been applied to the selective quantification of Cr(VI) in synthetic samples and wastewater samples with the satisfactory results. PMID:18321770

  15. The RNA 3D Motif Atlas: Computational methods for extraction, organization and evaluation of RNA motifs.

    PubMed

    Parlea, Lorena G; Sweeney, Blake A; Hosseini-Asanjan, Maryam; Zirbel, Craig L; Leontis, Neocles B

    2016-07-01

    RNA 3D motifs occupy places in structured RNA molecules that correspond to the hairpin, internal and multi-helix junction "loops" of their secondary structure representations. As many as 40% of the nucleotides of an RNA molecule can belong to these structural elements, which are distinct from the regular double helical regions formed by contiguous AU, GC, and GU Watson-Crick basepairs. With the large number of atomic- or near atomic-resolution 3D structures appearing in a steady stream in the PDB/NDB structure databases, the automated identification, extraction, comparison, clustering and visualization of these structural elements presents an opportunity to enhance RNA science. Three broad applications are: (1) identification of modular, autonomous structural units for RNA nanotechnology, nanobiology and synthetic biology applications; (2) bioinformatic analysis to improve RNA 3D structure prediction from sequence; and (3) creation of searchable databases for exploring the binding specificities, structural flexibility, and dynamics of these RNA elements. In this contribution, we review methods developed for computational extraction of hairpin and internal loop motifs from a non-redundant set of high-quality RNA 3D structures. We provide a statistical summary of the extracted hairpin and internal loop motifs in the most recent version of the RNA 3D Motif Atlas. We also explore the reliability and accuracy of the extraction process by examining its performance in clustering recurrent motifs from homologous ribosomal RNA (rRNA) structures. We conclude with a summary of remaining challenges, especially with regard to extraction of multi-helix junction motifs. PMID:27125735

  16. Synthetic MUC1 Antitumor Vaccine Candidates with Varied Glycosylation Pattern Bearing R/S-configured Pam3 CysSerLys4.

    PubMed

    Shi, Lei; Cai, Hui; Huang, Zhi-Hua; Sun, Zhan-Yi; Chen, Yong-Xiang; Zhao, Yu-Fen; Kunz, Horst; Li, Yan-Mei

    2016-08-01

    The Toll-like receptor 2 ligand Pam3 CysSer is of particular interest for the construction synthetic vaccines because of its ability to stimulate of the innate immune system. Such vaccines usually comprise Pam3 CysSer with the natural R-configuration at the glycerol 2-position. Pam3 CysSer peptide vaccines with natural configuration have been shown to be more efficient than the corresponding R/S diastereomers. In order to clarify whether the effect of the configuration of Pam3 Cys on the immune response also applies to glycopeptide vaccines, MUC1 glycopeptide-lipopeptide vaccines bearing either R- or R/S-configured Pam3 CysSerLys4 were compared for their immunological effects. In order to find out whether glycosylated MUC1 tandem repeat domains comprise not only B-cell epitopes but also T-cell epitopes, two-component vaccines containing the Pam3 CysSerLys4 lipopeptide and MUC1 glycopeptides with various glycosylation patterns were synthesized, and their immune reactions in mice were studied. PMID:27188544

  17. Cross-Disciplinary Detection and Analysis of Network Motifs

    PubMed Central

    Tran, Ngoc Tam L; DeLuccia, Luke; McDonald, Aidan F; Huang, Chun-Hsi

    2015-01-01

    The detection of network motifs has recently become an important part of network analysis across all disciplines. In this work, we detected and analyzed network motifs from undirected and directed networks of several different disciplines, including biological network, social network, ecological network, as well as other networks such as airlines, power grid, and co-purchase of political books networks. Our analysis revealed that undirected networks are similar at the basic three and four nodes, while the analysis of directed networks revealed the distinction between networks of different disciplines. The study showed that larger motifs contained the three-node motif as a subgraph. Topological analysis revealed that similar networks have similar small motifs, but as the motif size increases, differences arise. Pearson correlation coefficient showed strong positive relationship between some undirected networks but inverse relationship between some directed networks. The study suggests that the three-node motif is a building block of larger motifs. It also suggests that undirected networks share similar low-level structures. Moreover, similar networks share similar small motifs, but larger motifs define the unique structure of individuals. Pearson correlation coefficient suggests that protein structure networks, dolphin social network, and co-authorships in network science belong to a superfamily. In addition, yeast protein–protein interaction network, primary school contact network, Zachary’s karate club network, and co-purchase of political books network can be classified into a superfamily. PMID:25983553

  18. Transcription factor motif quality assessment requires systematic comparative analysis

    PubMed Central

    Kibet, Caleb Kipkurui; Machanick, Philip

    2016-01-01

    Transcription factor (TF) binding site prediction remains a challenge in gene regulatory research due to degeneracy and potential variability in binding sites in the genome. Dozens of algorithms designed to learn binding models (motifs) have generated many motifs available in research papers with a subset making it to databases like JASPAR, UniPROBE and Transfac. The presence of many versions of motifs from the various databases for a single TF and the lack of a standardized assessment technique makes it difficult for biologists to make an appropriate choice of binding model and for algorithm developers to benchmark, test and improve on their models. In this study, we review and evaluate the approaches in use, highlight differences and demonstrate the difficulty of defining a standardized motif assessment approach. We review scoring functions, motif length, test data and the type of performance metrics used in prior studies as some of the factors that influence the outcome of a motif assessment. We show that the scoring functions and statistics used in motif assessment influence ranking of motifs in a TF-specific manner. We also show that TF binding specificity can vary by source of genomic binding data. We also demonstrate that information content of a motif is not in isolation a measure of motif quality but is influenced by TF binding behaviour. We conclude that there is a need for an easy-to-use tool that presents all available evidence for a comparative analysis. PMID:27092243

  19. Cross-disciplinary detection and analysis of network motifs.

    PubMed

    Tran, Ngoc Tam L; DeLuccia, Luke; McDonald, Aidan F; Huang, Chun-Hsi

    2015-01-01

    The detection of network motifs has recently become an important part of network analysis across all disciplines. In this work, we detected and analyzed network motifs from undirected and directed networks of several different disciplines, including biological network, social network, ecological network, as well as other networks such as airlines, power grid, and co-purchase of political books networks. Our analysis revealed that undirected networks are similar at the basic three and four nodes, while the analysis of directed networks revealed the distinction between networks of different disciplines. The study showed that larger motifs contained the three-node motif as a subgraph. Topological analysis revealed that similar networks have similar small motifs, but as the motif size increases, differences arise. Pearson correlation coefficient showed strong positive relationship between some undirected networks but inverse relationship between some directed networks. The study suggests that the three-node motif is a building block of larger motifs. It also suggests that undirected networks share similar low-level structures. Moreover, similar networks share similar small motifs, but larger motifs define the unique structure of individuals. Pearson correlation coefficient suggests that protein structure networks, dolphin social network, and co-authorships in network science belong to a superfamily. In addition, yeast protein-protein interaction network, primary school contact network, Zachary's karate club network, and co-purchase of political books network can be classified into a superfamily. PMID:25983553

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

    PubMed

    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. PMID:23874612

  1. Reconstructing genome mixtures from partial adjacencies.

    PubMed

    Mahmoody, Ahmad; Kahn, Crystal L; Raphael, Benjamin J

    2012-01-01

    Many cancer genome sequencing efforts are underway with the goal of identifying the somatic mutations that drive cancer progression. A major difficulty in these studies is that tumors are typically heterogeneous, with individual cells in a tumor having different complements of somatic mutations. However, nearly all DNA sequencing technologies sequence DNA from multiple cells, thus resulting in measurement of mutations from a mixture of genomes. Genome rearrangements are a major class of somatic mutations in many tumors, and the novel adjacencies (i.e. breakpoints) resulting from these rearrangements are readily detected from DNA sequencing reads. However, the assignment of each rearrangement, or adjacency, to an individual cancer genome in the mixture is not known. Moreover, the quantity of DNA sequence reads may be insufficient to measure all rearrangements in all genomes in the tumor. Motivated by this application, we formulate the k-minimum completion problem (k-MCP). In this problem, we aim to reconstruct k genomes derived from a single reference genome, given partial information about the adjacencies present in the mixture of these genomes. We show that the 1-MCP is solvable in linear time in the cases where: (i) the measured, incomplete genome has a single circular or linear chromosome; (ii) there are no restrictions on the chromosomal content of the measured, incomplete genome. We also show that the k-MCP problem, for k ≥ 3 in general, and the 2-MCP problem with the double-cut-and-join (DCJ) distance are NP-complete, when there are no restriction on the chromosomal structure of the measured, incomplete genome. These results lay the foundation for future algorithmic studies of the k-MCP and the application of these algorithms to real cancer sequencing data. PMID:23282028

  2. Structural motifs and the stability of fullerenes

    SciTech Connect

    Austin, S.J.; Fowler, P.W.; Manolopoulos, D.E.; Orlandi, G.; Zerbetto, F.

    1995-05-18

    Full geometry optimization has been performed within the semiempirical QCFF/PI model for the 1812 fullerene structural isomers of C{sub 60} formed by 12 pentagons and 20 hexagons. All are local minima on the potential energy hypersurface. Correlations of total energy with many structural motifs yield highly scattered diagrams, but some exhibit linear trends. Penalty and merit functions can be assigned to certain motifs: inclusion of a fused pentagon pair entails an average penalty of 111 kJ mol{sup -1}; a generic hexagon triple costs 23 kJ mol{sup -1}; a triple (open or fused) comprising a pentagon between two hexagonal neighbors gives a stabilization of 19 kJ mol{sup -1}. These results can be understood in terms of the curved nature of fullerene molecules: pentagons should be isolated to avoid sharp local curvature, hexagon triples are costly because they enforce local planarity and hence imply high curvature in another part of the fullerene surface, but hexagon-pentagon-hexagon triples allow the surface to distribute steric strain by warping. The best linear fit is found for H, the second moment of the hexagon-neighbor-index signature, which fits the total energies with a standard deviation of only 53 kJ mol{sup -1} and must be minimized for stability; this index too can be interpreted in terms of curvature. 26 refs., 5 figs.

  3. Structural motifs of pre-nucleation clusters.

    PubMed

    Zhang, Y; Türkmen, I R; Wassermann, B; Erko, A; Rühl, E

    2013-10-01

    Structural motifs of pre-nucleation clusters prepared in single, optically levitated supersaturated aqueous aerosol microparticles containing CaBr2 as a model system are reported. Cluster formation is identified by means of X-ray absorption in the Br K-edge regime. The salt concentration beyond the saturation point is varied by controlling the humidity in the ambient atmosphere surrounding the 15-30 μm microdroplets. This leads to the formation of metastable supersaturated liquid particles. Distinct spectral shifts in near-edge spectra as a function of salt concentration are observed, in which the energy position of the Br K-edge is red-shifted by up to 7.1 ± 0.4 eV if the dilute solution is compared to the solid. The K-edge positions of supersaturated solutions are found between these limits. The changes in electronic structure are rationalized in terms of the formation of pre-nucleation clusters. This assumption is verified by spectral simulations using first-principle density functional theory and molecular dynamics calculations, in which structural motifs are considered, explaining the experimental results. These consist of solvated CaBr2 moieties, rather than building blocks forming calcium bromide hexahydrates, the crystal system that is formed by drying aqueous CaBr2 solutions. PMID:24116574

  4. Peptoid nanosheets exhibit a new secondary-structure motif

    NASA Astrophysics Data System (ADS)

    Mannige, Ranjan V.; Haxton, Thomas K.; Proulx, Caroline; Robertson, Ellen J.; Battigelli, Alessia; Butterfoss, Glenn L.; Zuckermann, Ronald N.; Whitelam, Stephen

    2015-10-01

    A promising route to the synthesis of protein-mimetic materials that are capable of complex functions, such as molecular recognition and catalysis, is provided by sequence-defined peptoid polymers--structural relatives of biologically occurring polypeptides. Peptoids, which are relatively non-toxic and resistant to degradation, can fold into defined structures through a combination of sequence-dependent interactions. However, the range of possible structures that are accessible to peptoids and other biological mimetics is unknown, and our ability to design protein-like architectures from these polymer classes is limited. Here we use molecular-dynamics simulations, together with scattering and microscopy data, to determine the atomic-resolution structure of the recently discovered peptoid nanosheet, an ordered supramolecular assembly that extends macroscopically in only two dimensions. Our simulations show that nanosheets are structurally and dynamically heterogeneous, can be formed only from peptoids of certain lengths, and are potentially porous to water and ions. Moreover, their formation is enabled by the peptoids' adoption of a secondary structure that is not seen in the natural world. This structure, a zigzag pattern that we call a Σ(`sigma')-strand, results from the ability of adjacent backbone monomers to adopt opposed rotational states, thereby allowing the backbone to remain linear and untwisted. Linear backbones tiled in a brick-like way form an extended two-dimensional nanostructure, the Σ-sheet. The binary rotational-state motif of the Σ-strand is not seen in regular protein structures, which are usually built from one type of rotational state. We also show that the concept of building regular structures from multiple rotational states can be generalized beyond the peptoid nanosheet system.

  5. NIR-Triggered Rapid Shape Memory PAM-GO-Gelatin Hydrogels with High Mechanical Strength.

    PubMed

    Huang, Jiahe; Zhao, Lei; Wang, Tao; Sun, Weixiang; Tong, Zhen

    2016-05-18

    Shape memory hydrogels containing over 76 wt % of water were synthesized in a one-pot method, and interpenetrating double network was formed by physically cross-linked gelatin network and chemically cross-linked polyacrylamide (PAM) network with graphene oxide (GO). The temporary shape was quickly fixed by cooling in ice water for 30 s after deformation at 80 °C for 10 s. Shape recovery started in 10 s under near-infrared (NIR) irradiation and almost completed within 60 s depending on the curling angle. A small amount of GO in the hydrogels (≤1.5 mg/mL) played a key role in NIR energy absorption and transformation into thermal energy. The hydrogel without GO showed no response to the NIR irradiation and cannot recover to its permanent shape by NIR irradiation. Temperature sweep was conducted in the cycle of 20 °C → 80 °C → 20 °C, and the structure change in the hydrogels with temperature was investigated according to the storage modulus G' and tangent of the loss angle tan δ as a function of the hydrogel composition. The shape-memory capability was confirmed as the contribution from the triple-helix cross-linking network of gelatin. High mechanical toughness (strength > 400 kPa and broken strain > 500%) was achieved by the double-network with the sacrificial gelatin network and GO bridging to dissipate deformation energy. The optimized composition of the hydrogel was found to be a key point to realize stable temporary shape and rapid recovery to the permanent shape controlled by NIR irradiation with reasonable strength. The facile preparation and noncontact gentle stimulus of the present hydrogel hold great potential to be used in soft actuator materials. PMID:27116394

  6. Network Motifs: Simple Building Blocks of Complex Networks

    NASA Astrophysics Data System (ADS)

    Milo, R.; Shen-Orr, S.; Itzkovitz, S.; Kashtan, N.; Chklovskii, D.; Alon, U.

    2002-10-01

    Complex networks are studied across many fields of science. To uncover their structural design principles, we defined ``network motifs,'' patterns of interconnections occurring in complex networks at numbers that are significantly higher than those in randomized networks. We found such motifs in networks from biochemistry, neurobiology, ecology, and engineering. The motifs shared by ecological food webs were distinct from the motifs shared by the genetic networks of Escherichia coli and Saccharomyces cerevisiae or from those found in the World Wide Web. Similar motifs were found in networks that perform information processing, even though they describe elements as different as biomolecules within a cell and synaptic connections between neurons in Caenorhabditis elegans. Motifs may thus define universal classes of networks. This approach may uncover the basic building blocks of most networks.

  7. A Gibbs sampler for motif detection in phylogenetically close sequences

    NASA Astrophysics Data System (ADS)

    Siddharthan, Rahul; van Nimwegen, Erik; Siggia, Eric

    2004-03-01

    Genes are regulated by transcription factors that bind to DNA upstream of genes and recognize short conserved ``motifs'' in a random intergenic ``background''. Motif-finders such as the Gibbs sampler compare the probability of these short sequences being represented by ``weight matrices'' to the probability of their arising from the background ``null model'', and explore this space (analogous to a free-energy landscape). But closely related species may show conservation not because of functional sites but simply because they have not had sufficient time to diverge, so conventional methods will fail. We introduce a new Gibbs sampler algorithm that accounts for common ancestry when searching for motifs, while requiring minimal ``prior'' assumptions on the number and types of motifs, assessing the significance of detected motifs by ``tracking'' clusters that stay together. We apply this scheme to motif detection in sporulation-cycle genes in the yeast S. cerevisiae, using recent sequences of other closely-related Saccharomyces species.

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

    SciTech Connect

    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.

  9. Ballast: A Ball-based Algorithm for Structural Motifs

    PubMed Central

    He, Lu; Vandin, Fabio; Pandurangan, Gopal

    2013-01-01

    Abstract Structural motifs encapsulate local sequence-structure-function relationships characteristic of related proteins, enabling the prediction of functional characteristics of new proteins, providing molecular-level insights into how those functions are performed, and supporting the development of variants specifically maintaining or perturbing function in concert with other properties. Numerous computational methods have been developed to search through databases of structures for instances of specified motifs. However, it remains an open problem how best to leverage the local geometric and chemical constraints underlying structural motifs in order to develop motif-finding algorithms that are both theoretically and practically efficient. We present a simple, general, efficient approach, called Ballast (ball-based algorithm for structural motifs), to match given structural motifs to given structures. Ballast combines the best properties of previously developed methods, exploiting the composition and local geometry of a structural motif and its possible instances in order to effectively filter candidate matches. We show that on a wide range of motif-matching problems, Ballast efficiently and effectively finds good matches, and we provide theoretical insights into why it works well. By supporting generic measures of compositional and geometric similarity, Ballast provides a powerful substrate for the development of motif-matching algorithms. PMID:23383999

  10. Gibbs motif sampling: detection of bacterial outer membrane protein repeats.

    PubMed Central

    Neuwald, A. F.; Liu, J. S.; Lawrence, C. E.

    1995-01-01

    The detection and alignment of locally conserved regions (motifs) in multiple sequences can provide insight into protein structure, function, and evolution. A new Gibbs sampling algorithm is described that detects motif-encoding regions in sequences and optimally partitions them into distinct motif models; this is illustrated using a set of immunoglobulin fold proteins. When applied to sequences sharing a single motif, the sampler can be used to classify motif regions into related submodels, as is illustrated using helix-turn-helix DNA-binding proteins. Other statistically based procedures are described for searching a database for sequences matching motifs found by the sampler. When applied to a set of 32 very distantly related bacterial integral outer membrane proteins, the sampler revealed that they share a subtle, repetitive motif. Although BLAST (Altschul SF et al., 1990, J Mol Biol 215:403-410) fails to detect significant pairwise similarity between any of the sequences, the repeats present in these outer membrane proteins, taken as a whole, are highly significant (based on a generally applicable statistical test for motifs described here). Analysis of bacterial porins with known trimeric beta-barrel structure and related proteins reveals a similar repetitive motif corresponding to alternating membrane-spanning beta-strands. These beta-strands occur on the membrane interface (as opposed to the trimeric interface) of the beta-barrel. The broad conservation and structural location of these repeats suggests that they play important functional roles. PMID:8520488

  11. Invisible RNA state dynamically couples distant motifs

    PubMed Central

    Lee, Janghyun; Dethoff, Elizabeth A.; Al-Hashimi, Hashim M.

    2014-01-01

    Using on- and off-resonance carbon and nitrogen R1ρ NMR relaxation dispersion in concert with mutagenesis and NMR chemical shift fingerprinting, we show that the transactivation response element RNA from the HIV-1 exists in dynamic equilibrium with a transient state that has a lifetime of ∼2 ms and population of ∼0.4%, which simultaneously remodels the structure of a bulge, stem, and apical loop. This is accomplished by a global change in strand register, in which bulge residues pair up with residues in the upper stem, causing a reshuffling of base pairs that propagates to the tip of apical loop, resulting in the creation of three noncanonical base pairs. Our results show that transient states can remodel distant RNA motifs and possibly give rise to mechanisms for rapid long-range communication in RNA that can be harnessed in processes such as cooperative folding and ribonucleoprotein assembly. PMID:24979799

  12. An RNA motif that binds ATP

    NASA Technical Reports Server (NTRS)

    Sassanfar, M.; Szostak, J. W.

    1993-01-01

    RNAs that contain specific high-affinity binding sites for small molecule ligands immobilized on a solid support are present at a frequency of roughly one in 10(10)-10(11) in pools of random sequence RNA molecules. Here we describe a new in vitro selection procedure designed to ensure the isolation of RNAs that bind the ligand of interest in solution as well as on a solid support. We have used this method to isolate a remarkably small RNA motif that binds ATP, a substrate in numerous biological reactions and the universal biological high-energy intermediate. The selected ATP-binding RNAs contain a consensus sequence, embedded in a common secondary structure. The binding properties of ATP analogues and modified RNAs show that the binding interaction is characterized by a large number of close contacts between the ATP and RNA, and by a change in the conformation of the RNA.

  13. Exchange coupling between laterally adjacent nanomagnets.

    PubMed

    Dey, H; Csaba, G; Bernstein, G H; Porod, W

    2016-09-30

    We experimentally demonstrate exchange-coupling between laterally adjacent nanomagnets. Our results show that two neighboring nanomagnets that are each antiferromagnetically exchange-coupled to a common ferromagnetic bottom layer can be brought into strong ferromagnetic interaction. Simulations show that interlayer exchange coupling effectively promotes ferromagnetic alignment between the two nanomagnets, as opposed to antiferromagnetic alignment due to dipole-coupling. In order to experimentally demonstrate the proposed scheme, we fabricated arrays of pairs of elongated, single-domain nanomagnets. Magnetic force microscopy measurements show that most of the pairs are ferromagnetically ordered. The results are in agreement with micromagnetic simulations. The presented scheme can achieve coupling strengths that are significantly stronger than dipole coupling, potentially enabling far-reaching applications in Nanomagnet Logic, spin-wave devices and three-dimensional storage and computing. PMID:27535227

  14. Seismicity in Azerbaijan and Adjacent Caspian Sea

    SciTech Connect

    Panahi, Behrouz M.

    2006-03-23

    So far no general view on the geodynamic evolution of the Black Sea to the Caspian Sea region is elaborated. This is associated with the geological and structural complexities of the region revealed by geophysical, geochemical, petrologic, structural, and other studies. A clash of opinions on geodynamic conditions of the Caucasus region, sometimes mutually exclusive, can be explained by a simplified interpretation of the seismic data. In this paper I analyze available data on earthquake occurrences in Azerbaijan and the adjacent Caspian Sea region. The results of the analysis of macroseismic and instrumental data, seismic regime, and earthquake reoccurrence indicate that a level of seismicity in the region is moderate, and seismic event are concentrated in the shallow part of the lithosphere. Seismicity is mostly intra-plate, and spatial distribution of earthquake epicenters does not correlate with the plate boundaries.

  15. Boundary Layers of Air Adjacent to Cylinders

    PubMed Central

    Nobel, Park S.

    1974-01-01

    Using existing heat transfer data, a relatively simple expression was developed for estimating the effective thickness of the boundary layer of air surrounding cylinders. For wind velocities from 10 to 1000 cm/second, the calculated boundary-layer thickness agreed with that determined for water vapor diffusion from a moistened cylindrical surface 2 cm in diameter. It correctly predicted the resistance for water vapor movement across the boundary layers adjacent to the (cylindrical) inflorescence stems of Xanthorrhoea australis R. Br. and Scirpus validus Vahl and the leaves of Allium cepa L. The boundary-layer thickness decreased as the turbulence intensity increased. For a turbulence intensity representative of field conditions (0.5) and for νwindd between 200 and 30,000 cm2/second (where νwind is the mean wind velocity and d is the cylinder diameter), the effective boundary-layer thickness in centimeters was equal to [Formula: see text]. PMID:16658855

  16. Design and Synthesis of Systemically Active Metabotropic Glutamate Subtype-2 and -3 (mGlu2/3) Receptor Positive Allosteric Modulators (PAMs): Pharmacological Characterization and Assessment in a Rat Model of Cocaine Dependence

    PubMed Central

    2015-01-01

    As part of our ongoing small-molecule metabotropic glutamate (mGlu) receptor positive allosteric modulator (PAM) research, we performed structure–activity relationship (SAR) studies around a series of group II mGlu PAMs. Initial analogues exhibited weak activity as mGlu2 receptor PAMs and no activity at mGlu3. Compound optimization led to the identification of potent mGlu2/3 selective PAMs with no in vitro activity at mGlu1,4–8 or 45 other CNS receptors. In vitro pharmacological characterization of representative compound 44 indicated agonist-PAM activity toward mGlu2 and PAM activity at mGlu3. The most potent mGlu2/3 PAMs were characterized in assays predictive of ADME/T and pharmacokinetic (PK) properties, allowing the discovery of systemically active mGlu2/3 PAMs. On the basis of its overall profile, compound 74 was selected for behavioral studies and was shown to dose-dependently decrease cocaine self-administration in rats after intraperitoneal administration. These mGlu2/3 receptor PAMs have significant potential as small molecule tools for investigating group II mGlu pharmacology. PMID:24735492

  17. Encoded Expansion: An Efficient Algorithm to Discover Identical String Motifs

    PubMed Central

    Azmi, Aqil M.; Al-Ssulami, Abdulrakeeb

    2014-01-01

    A major task in computational biology is the discovery of short recurring string patterns known as motifs. Most of the schemes to discover motifs are either stochastic or combinatorial in nature. Stochastic approaches do not guarantee finding the correct motifs, while the combinatorial schemes tend to have an exponential time complexity with respect to motif length. To alleviate the cost, the combinatorial approach exploits dynamic data structures such as trees or graphs. Recently (Karci (2009) Efficient automatic exact motif discovery algorithms for biological sequences, Expert Systems with Applications 36:7952–7963) devised a deterministic algorithm that finds all the identical copies of string motifs of all sizes in theoretical time complexity of and a space complexity of where is the length of the input sequence and is the length of the longest possible string motif. In this paper, we present a significant improvement on Karci's original algorithm. The algorithm that we propose reports all identical string motifs of sizes that occur at least times. Our algorithm starts with string motifs of size 2, and at each iteration it expands the candidate string motifs by one symbol throwing out those that occur less than times in the entire input sequence. We use a simple array and data encoding to achieve theoretical worst-case time complexity of and a space complexity of Encoding of the substrings can speed up the process of comparison between string motifs. Experimental results on random and real biological sequences confirm that our algorithm has indeed a linear time complexity and it is more scalable in terms of sequence length than the existing algorithms. PMID:24871320

  18. Evaluation of an Indigenously Prepared Herbal Extract (EndoPam) as an Antimicrobial Endodontic Irrigant: An Ex Vivo Study

    PubMed Central

    Mathew, Jain; Pathrose, Sonia; Kottoor, Jojo; Karaththodiyil, Ranjith; Alani, Mathew; Mathew, Joy

    2015-01-01

    Backgroundg: Root canal irrigation plays a pivotal role in endodontics. Constant increase in antibiotic resistance and side effects caused by synthetic irrigants has shifted the research toward developing herbal alternatives. The current study aims to assess the ex vivo effectiveness of an indigenously prepared herbal extract “EndoPam” and compare it with the conventional endodontic irrigants for disinfection of root canals infected with Enterococcus faecalis. Materials and Methods: As a preliminary study of the antimicrobial efficacy of the test irrigants, an Agar diffusion study was conducted, and zone of inhibition measured. Forty extracted mandibular premolars with straight root canals were selected and standardized to 12 ± 1 mm in length. Root canals were prepared using rotary ProTaper system until F3 instrument and were infected with the culture of E. faecalis for three weeks. Specimens were divided into four groups (n = 10). Group 1: EndoPam ( Ingredients: Syzigium aromaticum, Eucalyptus globulus, Cinnamomum zeylanicum and Mentha piperita), Group 2: 2% chlorhexidine, Group 3: 5.25% Sodium hypochlorite, Group 4: Normal Saline. Irrigation was performed for each group. Samples were inoculated and incubated for 24 h at 37°C for qualitative analysis qualitative analysis. Results: In the preliminary Agar diffusion study, EndoPam exhibited a zone of inhibition comparable to that of sodium hypochrorite. The diameter of the inhibition zone was in the following order: 2% chlorhexidine gluconate > EndoPam > 5.25% NaOCl > Normal Saline. The qualitative assay done by culturing the bacteria after a period of 3 weeks showed no bacterial growth in any of the tested irrigants, except in normal saline. Conclusion: It was found that the experimental product was as effective as conventional irrigants in reducing the microbial count. PMID:26124607

  19. Nonviral gene therapy in vivo with PAM-RG4/apoptin as a potential brain tumor therapeutic

    PubMed Central

    An, Songhie; Nam, Kihoon; Choi, Sunghyun; Bai, Cheng Z; Lee, Yan; Park, Jong-Sang

    2013-01-01

    Background Glioma is still one of the most complicated forms of brain tumor to remove completely due to its location and the lack of an efficient means to specifically eliminate tumor cells. For these reasons, this study has examined the effectiveness of a nonviral gene therapy approach utilizing a tumor-selective killer gene on a brain tumor xenograft model. Methods and results The therapeutic apoptin gene was recombined into the JDK plasmid and delivered into human brain tumor cells (U87MG) by using a polyamidoamine dendrimer with an arginine surface (PAM-RG4). Studies in vitro showed that the PAM-RG4/apoptin plasmid polyplex exhibited a particularly high transfection activity of .40%. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, 4′,6-Diamidino-2-phenylindole (DAPI) TUNEL assay, DAPI staining, and caspase-3 activity assay verified that the tumor cells had undergone apoptosis induced by apoptin. For in vivo studies, the polyplex was injected into tumors, which were induced by injecting U87MG cells intradermally into nude mice. Based on hematoxylin and eosin staining, epidermal growth factor receptor immunohistochemistry results and tumor volume measurement results, tumor growth was effectively inhibited and no specific edema, irritation, or other harm to the skin was observed after polyplex injection. The in vivo expression of apoptin and the induction of apoptosis were verified by reverse-transcription polymerase chain reaction analysis, TUNEL assay, and DAPI staining. Conclusion The PAM-RG4/apoptin gene polyplex is a strong candidate for brain tumor therapeutics because of the synergistic effect of the carrier’s high transfection efficiency (35%–40%) in glioma cells and the selective apoptosis-inducing activity of apoptin in tumor cells. PMID:23589689

  20. 30 CFR 56.9103 - Clearance on adjacent tracks.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Clearance on adjacent tracks. 56.9103 Section..., Hauling, and Dumping Traffic Safety § 56.9103 Clearance on adjacent tracks. Railcars shall not be left on side tracks unless clearance is provided for traffic on adjacent tracks....

  1. 30 CFR 57.9103 - Clearance on adjacent tracks.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Clearance on adjacent tracks. 57.9103 Section..., Hauling, and Dumping Traffic Safety § 57.9103 Clearance on adjacent tracks. Railcars shall not be left on side tracks unless clearance is provided for traffic on adjacent tracks....

  2. 30 CFR 56.9103 - Clearance on adjacent tracks.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Clearance on adjacent tracks. 56.9103 Section..., Hauling, and Dumping Traffic Safety § 56.9103 Clearance on adjacent tracks. Railcars shall not be left on side tracks unless clearance is provided for traffic on adjacent tracks....

  3. 30 CFR 57.9103 - Clearance on adjacent tracks.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Clearance on adjacent tracks. 57.9103 Section..., Hauling, and Dumping Traffic Safety § 57.9103 Clearance on adjacent tracks. Railcars shall not be left on side tracks unless clearance is provided for traffic on adjacent tracks....

  4. 33 CFR 80.1395 - Puget Sound and adjacent waters.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Puget Sound and adjacent waters... INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Thirteenth District § 80.1395 Puget Sound and adjacent waters. The 72 COLREGS shall apply on all waters of Puget Sound and adjacent waters, including Lake...

  5. 33 CFR 80.1395 - Puget Sound and adjacent waters.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Puget Sound and adjacent waters... INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Thirteenth District § 80.1395 Puget Sound and adjacent waters. The 72 COLREGS shall apply on all waters of Puget Sound and adjacent waters, including Lake...

  6. 33 CFR 80.1395 - Puget Sound and adjacent waters.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Puget Sound and adjacent waters... INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Thirteenth District § 80.1395 Puget Sound and adjacent waters. The 72 COLREGS shall apply on all waters of Puget Sound and adjacent waters, including Lake...

  7. 33 CFR 80.1395 - Puget Sound and adjacent waters.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Puget Sound and adjacent waters... INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Thirteenth District § 80.1395 Puget Sound and adjacent waters. The 72 COLREGS shall apply on all waters of Puget Sound and adjacent waters, including Lake...

  8. 33 CFR 80.1395 - Puget Sound and adjacent waters.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 1 2012-07-01 2012-07-01 false Puget Sound and adjacent waters... INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Thirteenth District § 80.1395 Puget Sound and adjacent waters. The 72 COLREGS shall apply on all waters of Puget Sound and adjacent waters, including Lake...

  9. Experimental study of 112 Gb/s short reach transmission employing PAM formats and SiP intensity modulator at 1.3 μm.

    PubMed

    Chagnon, Mathieu; Osman, Mohamed; Poulin, Michel; Latrasse, Christine; Gagné, Jean-Frédéric; Painchaud, Yves; Paquet, Carl; Lessard, Stéphane; Plant, David

    2014-08-25

    We present a Silicon Photonic (SiP) intensity modulator operating at 1.3 μm with pulse amplitude modulation formats for short reach transmission employing a digital to analog converter for the RF signal generator, enabling pulse shaping and precompensation of the transmitter's frequency response. Details of the SiP Mach-Zehnder interfometer are presented. We study the system performance at various bit rates, PAM orders and propagation distances. To the best of our knowledge, we report the first demonstration of a 112 Gb/s transmission over 10 km of SMF fiber operating below pre-FEC BER threshold of 3.8 × 10(-3) employing PAM-8 at 37.4 Gbaud using a fully packaged SiP modulator. An analytical model for the Q-factor metric applicable for multilevel PAM-N signaling is derived and accurately experimentally verified in the case of Gaussian noise limited detection. System performance is experimentally investigated and it is demonstrated that PAM order selection can be optimally chosen as a function of the desired throughput. We demonstrate the ability of the proposed transmitter to exhibit software-defined transmission for short reach applications by selecting PAM order, symbol rate and pulse shape. PMID:25321303

  10. Small-size two-axis mechanical devices for FPM and PAM using piezoelectronic actuators

    NASA Astrophysics Data System (ADS)

    Furuya, Mamoru; Araki, Tomohiro; Yamakawa, Shiro; Hisada, Yasumasa; Kondo, Fumika; Akiba, Toshikatsu

    1998-05-01

    We have developed two kinds of small size and light weight mechanical devices which consist of 2-axis piezoelectronic driving actuators and elastic hinges for fine pointing mechanism (FPM) and point ahead mechanism (PAM) optical inter- orbit communication (optical IOC) equipment. These are 'Beam Trapping Mechanism (BTM)' and 'Beam Scanning Mechanism (BSM)' respectively. High sensitivity receive system using single- mode optical fiber should be needed to increase communication data rate, which are a receiver of heterodyne detection in optical fiber and a receiver using optical pre-amplifier (for example, Er doped fiber amplifier). Therefore, both improvement of precision of FPM and control of the end of optical fiber are needed. In order to realize these requirements, we have designed, developed and tested two kinds of mechanical devices. At first, results of BTM, which consists of an optical fiber, four piezoelectric actuators, elastic hinges and a housing which mounts them, are described. The end facet of optical fiber supported by elastic hinges is controlled by piezoelectronic actuators in order to trap spatial received beam into optical fiber with high efficiency and high speed. The functional test results of BTM show a moving range of 140 (mu) rad, a resolution of less than 0.2 (mu) rad and natural frequency of 390 Hz. These values show BTM has enough performance for low-loss received beam trapping into optical fiber core. Furthermore, small-sized and lightweight BTM was realized using piezoelectronic actuators. We designed a BSM which has function of piezoelectronic driving 2-axis FPM in order to improve FPM. BSM have mirror of which size is 15 * 12 mm2. The mechanical concept of BSM is as same as BTM. In BSM, mirror is supported by elastic hinges, replace with optical fiber. Function test results show scanning angle range of more than 2.8 mrad at azimuth direction, 2.0 mrad at elevation direction, scanning resolution of 1.0 (mu) rad and natural frequency is

  11. Identifying novel sequence variants of RNA 3D motifs

    PubMed Central

    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

  12. Stochastic EM-based TFBS motif discovery with MITSU

    PubMed Central

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

    2014-01-01

    Motivation: 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. Results: 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. Availability and implementation: Java executable available for download at http://www.sourceforge.net/p/mitsu-motif/, supported on Linux/OS X. Contact: a.m.kilpatrick@sms.ed.ac.uk PMID:24931999

  13. Identifying novel sequence variants of RNA 3D motifs.

    PubMed

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

    2015-09-01

    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

  14. The phenomenon of astral motifs on late mediaeval tombstones

    NASA Astrophysics Data System (ADS)

    Mijatović, V.; Ninković, S.; Vemić, D.

    2003-10-01

    The authors study astral motifs present on some mediaeval tombstones found in present-day Serbia and Montenegro and in the neighbouring countries (especially in Bosnia and Herzegovina). The authors discern some important astral motifs, explain them and present a short review concerning their frequency.

  15. DETAIL VIEW, MAIN ENTRANCE GATES, SHOWING A WINGED HOURGLASS MOTIF, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    DETAIL VIEW, MAIN ENTRANCE GATES, SHOWING A WINGED HOURGLASS MOTIF, WHICH REFERS TO THE QUICK PASSAGE OF TIME AND THE SHORTNESS OF HUMAN LIFE. USE OF THIS MOTIF WAS A CARRYOVER FROM THE MCARTHUR GATES. - Woodlands Cemetery, 4000 Woodlands Avenue, Philadelphia, Philadelphia County, PA

  16. Role of GxxxG Motifs in Transmembrane Domain Interactions.

    PubMed

    Teese, Mark G; Langosch, Dieter

    2015-08-25

    Transmembrane (TM) helices of integral membrane proteins can facilitate strong and specific noncovalent protein-protein interactions. Mutagenesis and structural analyses have revealed numerous examples in which the interaction between TM helices of single-pass membrane proteins is dependent on a GxxxG or (small)xxx(small) motif. It is therefore tempting to use the presence of these simple motifs as an indicator of TM helix interactions. In this Current Topic review, we point out that these motifs are quite common, with more than 50% of single-pass TM domains containing a (small)xxx(small) motif. However, the actual interaction strength of motif-containing helices depends strongly on sequence context and membrane properties. In addition, recent studies have revealed several GxxxG-containing TM domains that interact via alternative interfaces involving hydrophobic, polar, aromatic, or even ionizable residues that do not form recognizable motifs. In multipass membrane proteins, GxxxG motifs can be important for protein folding, and not just oligomerization. Our current knowledge thus suggests that the presence of a GxxxG motif alone is a weak predictor of protein dimerization in the membrane. PMID:26244771

  17. Differences in local genomic context of bound and unbound motifs

    PubMed Central

    Hansen, Loren; Mariño-Ramírez, Leonardo; Landsman, David

    2012-01-01

    Understanding gene regulation is a major objective in molecular biology research. Frequently, transcription is driven by transcription factors (TFs) that bind to specific DNA sequences. These motifs are usually short and degenerate, rendering the likelihood of multiple copies occurring throughout the genome due to random chance as high. Despite this, TFs only bind to a small subset of sites, thus prompting our investigation into the differences between motifs that are bound by TFs and those that remain unbound. Here we constructed vectors representing various chromatin- and sequence-based features for a published set of bound and unbound motifs representing nine TFs in the budding yeast Saccharomyces cerevisiae. Using a machine learning approach, we identified a set of features that can be used to discriminate between bound and unbound motifs. We also discovered that some TFs bind most or all of their strong motifs in intergenic regions. Our data demonstrate that local sequence context can be strikingly different around motifs that are bound compared to motifs that are unbound. We concluded that there are multiple combinations of genomic features that characterize bound or unbound motifs. PMID:22692006

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

    PubMed Central

    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; Paś, 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. PMID:19920119

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

    ERIC Educational Resources Information Center

    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)

  20. A sialoreceptor binding motif in the Mycoplasma synoviae adhesin VlhA.

    PubMed

    May, Meghan; Dunne, Dylan W; Brown, Daniel R

    2014-01-01

    Mycoplasma synoviae depends on its adhesin VlhA to mediate cytadherence to sialylated host cell receptors. Allelic variants of VlhA arise through recombination between an assemblage of promoterless vlhA pseudogenes and a single transcription promoter site, creating lineages of M. synoviae that each express a different vlhA allele. The predicted full-length VlhA sequences adjacent to the promoter of nine lineages of M. synoviae varying in avidity of cytadherence were aligned with that of the reference strain MS53 and with a 60-a.a. hemagglutinating VlhA C-terminal fragment from a Tunisian lineage of strain WVU1853(T). Seven different sequence variants of an imperfectly conserved, single-copy, 12-a.a. candidate cytadherence motif were evident amid the flanking variable residues of the 11 total sequences examined. The motif was predicted to adopt a short hairpin structure in a low-complexity region near the C-terminus of VlhA. Biotinylated synthetic oligopeptides representing four selected variants of the 12-a.a. motif, with the whole synthesized 60-a.a. fragment as a positive control, differed (P<0.01) in the extent they bound to chicken erythrocyte membranes. All bound to a greater extent (P<0.01) than scrambled or irrelevant VlhA domain negative control peptides did. Experimentally introduced branched-chain amino acid (BCAA) substitutions Val3Ile and Leu7Ile did not significantly alter binding, whereas fold-destabilizing substitutions Thr4Gly and Ala9Gly tended to reduce it (P<0.05). Binding was also reduced to background levels (P<0.01) when the peptides were exposed to desialylated membranes, or were pre-saturated with free sialic acid before exposure to untreated membranes. From this evidence we conclude that the motif P-X-(BCAA)-X-F-X-(BCAA)-X-A-K-X-G binds sialic acid and likely mediates VlhA-dependent M. synoviae attachment to host cells. This conserved mechanism retains the potential for fine-scale rheostasis in binding avidity, which could be a general

  1. A Sialoreceptor Binding Motif in the Mycoplasma synoviae Adhesin VlhA

    PubMed Central

    May, Meghan; Dunne, Dylan W.; Brown, Daniel R.

    2014-01-01

    Mycoplasma synoviae depends on its adhesin VlhA to mediate cytadherence to sialylated host cell receptors. Allelic variants of VlhA arise through recombination between an assemblage of promoterless vlhA pseudogenes and a single transcription promoter site, creating lineages of M. synoviae that each express a different vlhA allele. The predicted full-length VlhA sequences adjacent to the promoter of nine lineages of M. synoviae varying in avidity of cytadherence were aligned with that of the reference strain MS53 and with a 60-a.a. hemagglutinating VlhA C-terminal fragment from a Tunisian lineage of strain WVU1853T. Seven different sequence variants of an imperfectly conserved, single-copy, 12-a.a. candidate cytadherence motif were evident amid the flanking variable residues of the 11 total sequences examined. The motif was predicted to adopt a short hairpin structure in a low-complexity region near the C-terminus of VlhA. Biotinylated synthetic oligopeptides representing four selected variants of the 12-a.a. motif, with the whole synthesized 60-a.a. fragment as a positive control, differed (P<0.01) in the extent they bound to chicken erythrocyte membranes. All bound to a greater extent (P<0.01) than scrambled or irrelevant VlhA domain negative control peptides did. Experimentally introduced branched-chain amino acid (BCAA) substitutions Val3Ile and Leu7Ile did not significantly alter binding, whereas fold-destabilizing substitutions Thr4Gly and Ala9Gly tended to reduce it (P<0.05). Binding was also reduced to background levels (P<0.01) when the peptides were exposed to desialylated membranes, or were pre-saturated with free sialic acid before exposure to untreated membranes. From this evidence we conclude that the motif P-X-(BCAA)-X-F-X-(BCAA)-X-A-K-X-G binds sialic acid and likely mediates VlhA-dependent M. synoviae attachment to host cells. This conserved mechanism retains the potential for fine-scale rheostasis in binding avidity, which could be a general

  2. De Novo Regulatory Motif Discovery Identifies Significant Motifs in Promoters of Five Classes of Plant Dehydrin Genes

    PubMed Central

    Zolotarov, Yevgen; Strömvik, Martina

    2015-01-01

    Plants accumulate dehydrins in response to osmotic stresses. Dehydrins are divided into five different classes, which are thought to be regulated in different manners. To better understand differences in transcriptional regulation of the five dehydrin classes, de novo motif discovery was performed on 350 dehydrin promoter sequences from a total of 51 plant genomes. Overrepresented motifs were identified in the promoters of five dehydrin classes. The Kn dehydrin promoters contain motifs linked with meristem specific expression, as well as motifs linked with cold/dehydration and abscisic acid response. KS dehydrin promoters contain a motif with a GATA core. SKn and YnSKn dehydrin promoters contain motifs that match elements connected with cold/dehydration, abscisic acid and light response. YnKn dehydrin promoters contain motifs that match abscisic acid and light response elements, but not cold/dehydration response elements. Conserved promoter motifs are present in the dehydrin classes and across different plant lineages, indicating that dehydrin gene regulation is likely also conserved. PMID:26114291

  3. Evaluating the effects of allelochemical ferulic acid on Microcystis aeruginosa by pulse-amplitude-modulated (PAM) fluorometry and flow cytometry.

    PubMed

    Wang, Rui; Hua, Ming; Yu, Yang; Zhang, Min; Xian, Qi-Ming; Yin, Da-Qiang

    2016-03-01

    We investigated the effects of allelochemical ferulic acid (FA) on a series of physiological and biochemical processes of blue-green algae Microcystis aeruginosa, in order to find sensitive diagnostic variables for allelopathic effects. Algal cell density was significantly suppressed by FA (0.31-5.17 mM) only after 48 h exposure. Inhibitions of photosynthetic parameters (F(v)/F(m) and F(v)'/F(m)') occurred more rapidly than cell growth, and the stimulation of non-photochemical quenching was observed as a feed-back mechanisms induced by photosystem II blockage, determining by PAM fluorometry. Inhibitions on esterase activity, membrane potential and integrity, as well as disturbance on cell size, were all detected by flow cytometry with specific fluorescent markers, although exhibiting varied sensitivities. Membrane potential and esterase activity were identified as the most sensitive parameters (with relatively lower EC50 values), and responded more rapidly (significantly inhibited only after 8 h exposure) than photosynthetic parameters and cell growth, thus may be the primary responses of cyanobacteria to FA exposure. The use of PAM fluorometry and flow cytometry for rapid assessment of those sensitive variables may contribute to future mechanistic studies of allolepathic effects on phytoplankton. PMID:26766364

  4. IQCJ-SCHIP1, a novel fusion transcript encoding a calmodulin-binding IQ motif protein

    SciTech Connect

    Kwasnicka-Crawford, Dorota A. . E-mail: dakc@yorku.ca; Carson, Andrew R.; Scherer, Stephen W.

    2006-12-01

    The existence of transcripts that span two adjacent, independent genes is considered rare in the human genome. This study characterizes a novel human fusion gene named IQCJ-SCHIP1. IQCJ-SCHIP1 is the longest isoform of a complex transcriptional unit that bridges two separate genes that encode distinct proteins, IQCJ, a novel IQ motif containing protein and SCHIP1, a schwannomin interacting protein that has been previously shown to interact with the Neurofibromatosis type 2 (NF2) protein. IQCJ-SCHIP1 is located on the chromosome 3q25 and comprises a 1692-bp transcript encompassing 11 exons spanning 828 kb of the genomic DNA. We show that IQCJ-SCHIP1 mRNA is highly expressed in the brain. Protein encoded by the IQCJ-SCHIP1 gene was localized to cytoplasm and actin-rich regions and in differentiated PC12 cells was also seen in neurite extensions.

  5. Interaction between adjacent lightning discharges in clouds

    NASA Astrophysics Data System (ADS)

    Wang, Yanhui; Zhang, Guangshu; Zhang, Tong; Li, Yajun; Wu, Bin; Zhang, Tinglong

    2013-07-01

    Using a 3D lightning radiation source locating system (LLS), three pairs of associated lightning discharges (two or more adjacent lightning discharges following an arbitrary rule that their space-gap was less than 10 km and their time-gap was less than 800 ms) were observed, and the interaction between associated lightning discharges was analyzed. All these three pairs of associated lightning discharges were found to involve three or more charge regions (the ground was considered as a special charge region). Moreover, at least one charge region involved two lightning discharges per pair of associated lightning discharges. Identified from electric field changes, the subsequent lightning discharges were suppressed by the prior lightning discharges. However, it is possible that the prior lightning discharge provided a remaining discharge channel to facilitate the subsequent lightning discharge. The third case provided evidence of this possibility. Together, the results suggested that, if the charges in the main negative charge region can be consumed using artificial lightning above the main negative charge regions, lightning accidents on the ground could be greatly reduced, on the condition that the height of the main negative charge region and the charge intensity of the lower positive charge region are suitable.

  6. Full duplex fiber link for alternative wired and wireless access based on SSB optical millimeter-wave with 4-PAM signal

    NASA Astrophysics Data System (ADS)

    Ma, Jianxin; Zhang, Junjie

    2015-03-01

    A novel full-duplex fiber-wireless link based on single sideband (SSB) optical millimeter (mm)-wave with 10 Gbit/s 4-pulse amplitude modulation (PAM) signal is proposed to provide alternative wired and 40 GHz wireless accesses for the user terminals. The SSB optical mm-wave with 4-PAM signal consists of two tones: one bears the 4-PAM signal and the other is unmodulated with high power. After transmission over the fiber to the hybrid optical network unit (HONU), the SSB optical mm-wave signal can be decomposed by fiber Bragg gratings (FBGs) as the SSB optical mm-wave signal with reduced carrier-to-sideband ratio (the baseband 4-PAM optical signal) and the uplink optical carrier for the wireless (wired) access. This makes the HONU free from the laser source. For the uplink, since the wireless access signal is converted to the baseband by power detection, both the transmitter in the HONU and the receiver in optical line terminal (OLT) are co-shared for both wireless and wired accesses, which makes the full duplex link much simpler. In our scheme, the optical electrical field of the square-root increment level 4-PAM signal assures an equal level spacing receiving for both the downlink wired and wireless accesses. Since the downlink wireless signal is down-converted to the baseband by power detection, RF local oscillator is unnecessary. To confirm the feasibility of our proposed scheme, a simulation full duplex link with 40 GHz SSB optical mm-wave with 10 Gbit/s 4-PAM signal is built. The simulation results show that both down- and up-links for either wired or wireless access can keep good performance even if the link length of the SSMF is extended to 40 km.

  7. Tripartite motif 32 prevents pathological cardiac hypertrophy.

    PubMed

    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. PMID:26884348

  8. Tripartite motif 32 prevents pathological cardiac hypertrophy

    PubMed Central

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

    2016-01-01

    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. PMID:26884348

  9. A helix-turn motif in the C-terminal domain of histone H1.

    PubMed

    Vila, R; Ponte, I; Jiménez, M A; Rico, M; Suau, P

    2000-04-01

    The structural study of peptides belonging to the terminal domains of histone H1 can be considered as a step toward the understanding of the function of H1 in chromatin. The conformational properties of the peptide Ac-EPKRSVAFKKTKKEVKKVATPKK (CH-1), which belongs to the C-terminal domain of histone H1(o) (residues 99-121) and is adjacent to the central globular domain of the protein, were examined by means of 1H-NMR and circular dichroism. In aqueous solution, CH-1 behaved as a mainly unstructured peptide, although turn-like conformations in rapid equilibrium with the unfolded state could be present. Addition of trifluoroethanol resulted in a substantial increase of the helical content. The helical limits, as indicated by (i,i + 3) nuclear Overhauser effect (NOE) cross correlations and significant up-field conformational shifts of the C(alpha) protons, span from Pro100 to Val116, with Glu99 and Ala117 as N- and C-caps. A structure calculation performed on the basis of distance constraints derived from NOE cross peaks in 90% trifluoroethanol confirmed the helical structure of this region. The helical region has a marked amphipathic character, due to the location of all positively charged residues on one face of the helix and all the hydrophobic residues on the opposite face. The peptide has a TPKK motif at the C-terminus, following the alpha-helical region. The observed NOE connectivities suggest that the TPKK sequence adopts a type (I) beta-turn conformation, a sigma-turn conformation or a combination of both, in fast equilibrium with unfolded states. Sequences of the kind (S/T)P(K/R)(K/R) have been proposed as DNA binding motifs. The CH-1 peptide, thus, combines a positively charged amphipathic helix and a turn as potential DNA-binding motifs. PMID:10794405

  10. Talin-bound NPLY motif recruits integrin-signaling adapters to regulate cell spreading and mechanosensing

    PubMed Central

    Pinon, Perrine; Pärssinen, Jenita; Vazquez, Patricia; Bachmann, Michael; Rahikainen, Rolle; Jacquier, Marie-Claude; Azizi, Latifeh; Määttä, Juha A.; Bastmeyer, Martin; Hytönen, Vesa P.

    2014-01-01

    Integrin-dependent cell adhesion and spreading are critical for morphogenesis, tissue regeneration, and immune defense but also tumor growth. However, the mechanisms that induce integrin-mediated cell spreading and provide mechanosensing on different extracellular matrix conditions are not fully understood. By expressing β3-GFP-integrins with enhanced talin-binding affinity, we experimentally uncoupled integrin activation, clustering, and substrate binding from its function in cell spreading. Mutational analysis revealed Tyr747, located in the first cytoplasmic NPLY747 motif, to induce spreading and paxillin adapter recruitment to substrate- and talin-bound integrins. In addition, integrin-mediated spreading, but not focal adhesion localization, was affected by mutating adjacent sequence motifs known to be involved in kindlin binding. On soft, spreading-repellent fibronectin substrates, high-affinity talin-binding integrins formed adhesions, but normal spreading was only possible with integrins competent to recruit the signaling adapter protein paxillin. This proposes that integrin-dependent cell–matrix adhesion and cell spreading are independently controlled, offering new therapeutic strategies to modify cell behavior in normal and pathological conditions. PMID:24778313

  11. The CHH motif in sugar beet satellite DNA: a modulator for cytosine methylation.

    PubMed

    Zakrzewski, Falk; Schubert, Veit; Viehoever, Prisca; Minoche, André E; Dohm, Juliane C; Himmelbauer, Heinz; Weisshaar, Bernd; Schmidt, Thomas

    2014-06-01

    Methylation of DNA is important for the epigenetic silencing of repetitive DNA in plant genomes. Knowledge about the cytosine methylation status of satellite DNAs, a major class of repetitive DNA, is scarce. One reason for this is that arrays of tandemly arranged sequences are usually collapsed in next-generation sequencing assemblies. We applied strategies to overcome this limitation and quantified the level of cytosine methylation and its pattern in three satellite families of sugar beet (Beta vulgaris) which differ in their abundance, chromosomal localization and monomer size. We visualized methylation levels along pachytene chromosomes with respect to small satellite loci at maximum resolution using chromosome-wide fluorescent in situ hybridization complemented with immunostaining and super-resolution microscopy. Only reduced methylation of many satellite arrays was obtained. To investigate methylation at the nucleotide level we performed bisulfite sequencing of 1569 satellite sequences. We found that the level of methylation of cytosine strongly depends on the sequence context: cytosines in the CHH motif show lower methylation (44-52%), while CG and CHG motifs are more strongly methylated. This affects the overall methylation of satellite sequences because CHH occurs frequently while CG and CHG are rare or even absent in the satellite arrays investigated. Evidently, CHH is the major target for modulation of the cytosine methylation level of adjacent monomers within individual arrays and contributes to their epigenetic function. This strongly indicates that asymmetric cytosine methylation plays a role in the epigenetic modification of satellite repeats in plant genomes. PMID:24661787

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

    PubMed

    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 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. PMID:24912755

  13. Recurrent Structural Motifs in Non-Homologous Protein Structures

    PubMed Central

    Johansson, Maria U.; Zoete, Vincent; Guex, Nicolas

    2013-01-01

    We have extracted an extensive collection of recurrent structural motifs (RSMs), which consist of sequentially non-contiguous structural motifs (4–6 residues), each of which appears with very similar conformation in three or more mutually unrelated protein structures. We find that the proteins in our set are covered to a substantial extent by the recurrent non-contiguous structural motifs, especially the helix and strand regions. Computational alanine scanning calculations indicate that the average folding free energy changes upon alanine mutation for most types of non-alanine residues are higher for amino acids that are present in recurrent structural motifs than for amino acids that are not. The non-alanine amino acids that are most common in the recurrent structural motifs, i.e., phenylalanine, isoleucine, leucine, valine and tyrosine and the less abundant methionine and tryptophan, have the largest folding free energy changes. This indicates that the recurrent structural motifs, as we define them, describe recurrent structural patterns that are important for protein stability. In view of their properties, such structural motifs are potentially useful for inter-residue contact prediction and protein structure refinement. PMID:23574940

  14. BlockLogo: visualization of peptide and sequence motif conservation.

    PubMed

    Olsen, Lars Rønn; Kudahl, Ulrich Johan; Simon, Christian; Sun, Jing; Schönbach, Christian; Reinherz, Ellis L; Zhang, Guang Lan; Brusic, Vladimir

    2013-12-31

    BlockLogo is a web-server application for the visualization of protein and nucleotide fragments, continuous protein sequence motifs, and discontinuous sequence motifs using calculation of block entropy from multiple sequence alignments. The user input consists of a multiple sequence alignment, 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 and B-cell epitopes (both continuous and discontinuous). Our additional example shows a visualization and analysis of structural motifs that determine the specificity of peptide binding to HLA-DR molecules. The BlockLogo server also employs selected experimentally validated prediction algorithms to enable on-the-fly prediction of MHC binding affinity to 15 common HLA class I and class II alleles as well as visual analysis of discontinuous epitopes from multiple sequence alignments. It enables the visualization and analysis of structural and functional motifs that are usually described as regular expressions. It provides a compact view of discontinuous motifs composed of distant positions within biological sequences. BlockLogo is available at: http://research4.dfci.harvard.edu/cvc/blocklogo/ and http://met-hilab.bu.edu/blocklogo/. PMID:24001880

  15. Multiple Dileucine-like Motifs Direct VGLUT1 Trafficking

    PubMed Central

    Foss, Sarah M.; Li, Haiyan; Santos, Magda S.; Edwards, Robert H.

    2013-01-01

    The vesicular glutamate transporters (VGLUTs) package glutamate into synaptic vesicles, and the two principal isoforms VGLUT1 and VGLUT2 have been suggested to influence the properties of release. To understand how a VGLUT isoform might influence transmitter release, we have studied their trafficking and previously identified a dileucine-like endocytic motif in the C terminus of VGLUT1. Disruption of this motif impairs the activity-dependent recycling of VGLUT1, but does not eliminate its endocytosis. We now report the identification of two additional dileucine-like motifs in the N terminus of VGLUT1 that are not well conserved in the other isoforms. In the absence of all three motifs, rat VGLUT1 shows limited accumulation at synaptic sites and no longer responds to stimulation. In addition, shRNA-mediated knockdown of clathrin adaptor proteins AP-1 and AP-2 shows that the C-terminal motif acts largely via AP-2, whereas the N-terminal motifs use AP-1. Without the C-terminal motif, knockdown of AP-1 reduces the proportion of VGLUT1 that responds to stimulation. VGLUT1 thus contains multiple sorting signals that engage distinct trafficking mechanisms. In contrast to VGLUT1, the trafficking of VGLUT2 depends almost entirely on the conserved C-terminal dileucine-like motif: without this motif, a substantial fraction of VGLUT2 redistributes to the plasma membrane and the transporter's synaptic localization is disrupted. Consistent with these differences in trafficking signals, wild-type VGLUT1 and VGLUT2 differ in their response to stimulation. PMID:23804088

  16. Petroleum basins of Sakhalin and adjacent shelf

    SciTech Connect

    Mavrinski, Y.; Koblov, E. )

    1993-09-01

    Sixty-seven oil and gas fields have been discovered on Sakhalin and the adjacent shelf but the distribution of fields is uneven in north Sakhalin, south Sakhalin, and the Tatar basins. The sedimentary cover is composed of sandy, clayey, and siliceous rocks, with volcanogenic and coal-bearing deposits of Upper Cretaceous, Paleogene, and Neogene 8-12 km thick. Marine clayey and siliceous oil source rocks are regionally developed in the section at different stratigraphic levels; the organic matter is of mixed type and the content varies from 0.5 to 1.5%. The upper Oligocene and middle-upper Miocene source rocks in the north Sakhalin basin are typical, and the organic carbon content ranges from 1 to 5%. The level of organic matter catagenesis and conversion into hydrocarbons is high because of the high differential geothermal gradient in the basins, 30-50[degrees]C per km. Porous sandstones in the Miocene form the reservoirs in all fields with the exception of Okruzhnoye, where the pay zone is a siliceous claystone. Growth-fault rollovers and anticlines form the main traps ranging in area from 5 to 300 km[sup 2], with amplitudes between 100 and 600 m. both stratigraphic and structural traps have been identified. Considerable volumes of reserves are associated with the Miocene deposits of north Sakhalin, which are characterized by an optimum combination of oil source rocks, focused migration paths, and thick sequences of reservoirs and cap rocks. Six large fields have been discovered in the past 15 yr. Oil and condensate reserves stand at over 300 million MT, and gas reserves are about 900 billion m[sup 3].

  17. Coherent feedforward transcriptional regulatory motifs enhance drug resistance

    NASA Astrophysics Data System (ADS)

    Charlebois, Daniel A.; Balázsi, Gábor; Kærn, Mads

    2014-05-01

    Fluctuations in gene expression give identical cells access to a spectrum of phenotypes that can serve as a transient, nongenetic basis for natural selection by temporarily increasing drug resistance. In this study, we demonstrate using mathematical modeling and simulation that certain gene regulatory network motifs, specifically coherent feedforward loop motifs, can facilitate the development of nongenetic resistance by increasing cell-to-cell variability and the time scale at which beneficial phenotypic states can be maintained. Our results highlight how regulatory network motifs enabling transient, nongenetic inheritance play an important role in defining reproductive fitness in adverse environments and provide a selective advantage subject to evolutionary pressure.

  18. Seeing the B-A-C-H motif

    NASA Astrophysics Data System (ADS)

    Catravas, Palmyra

    2005-09-01

    Musical compositions can be thought of as complex, multidimensional data sets. Compositions based on the B-A-C-H motif (a four-note motif of the pitches of the last name of Johann Sebastian Bach) span several centuries of evolving compositional styles and provide an intriguing set for analysis since they contain a common feature, the motif, buried in dissimilar contexts. We will present analyses which highlight the content of this unusual set of pieces, with emphasis on visual display of information.

  19. Identification of Promoter Motifs Involved in the Network of Phytochrome A-Regulated Gene Expression by Combined Analysis of Genomic Sequence and Microarray Data1[w

    PubMed Central

    Hudson, Matthew E.; Quail, Peter H.

    2003-01-01

    Several hundred Arabidopsis genes, transcriptionally regulated by phytochrome A (phyA), were previously identified using an oligonucleotide microarray. We have now identified, in silico, conserved sequence motifs in the promoters of these genes by comparing the promoter sequences to those of all the genes present on the microarray from which they were sampled. This was done using a Perl script (called Sift) that identifies over-represented motifs using an enumerative approach. The utility of Sift was verified by analysis of circadian-regulated promoters known to contain a biologically significant motif. Several elements were then identified in phyA-responsive promoters by their over-representation. Five previously undescribed motifs were detected in the promoters of phyA-induced genes. Four novel motifs were found in phyA-repressed promoters, plus a motif that strongly resembles the DE1 element. The G-box, CACGTG, was a prominent hit in both induced and repressed phyA-responsive promoters. Intriguingly, two distinct flanking consensus sequences were observed adjacent to the G-box core sequence: one predominating in phyA-induced promoters, the other in phyA-repressed promoters. Such different conserved flanking nucleotides around the core motif in these two sets of promoters may indicate that different members of the same family of DNA-binding proteins mediate phyA induction and repression. An increased abundance of G-box sequences was observed in the most rapidly phyA-responsive genes and in the promoters of phyA-regulated transcription factors, indicating that G-box-binding transcription factors are upstream components in a transcriptional cascade that mediates phyA-regulated development. PMID:14681527

  20. A million peptide motifs for the molecular biologist.

    PubMed

    Tompa, Peter; Davey, Norman E; Gibson, Toby J; Babu, M Madan

    2014-07-17

    A molecular description of functional modules in the cell is the focus of many high-throughput studies in the postgenomic era. A large portion of biomolecular interactions in virtually all cellular processes is mediated by compact interaction modules, referred to as peptide motifs. Such motifs are typically less than ten residues in length, occur within intrinsically disordered regions, and are recognized and/or posttranslationally modified by structured domains of the interacting partner. In this review, we suggest that there might be over a million instances of peptide motifs in the human proteome. While this staggering number suggests that peptide motifs are numerous and the most understudied functional module in the cell, it also holds great opportunities for new discoveries. PMID:25038412

  1. 10. DETAIL OF CORNICE MOULDING WITH RAM'S HEAD MOTIF. EIGHT ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    10. DETAIL OF CORNICE MOULDING WITH RAM'S HEAD MOTIF. EIGHT SHADES OF GOLD LEAF AND BURNISHED GOLD LEAF WERE USED FOR THE INTERIOR FINISHES - Anaconda Historic District, Washoe Theater, 305 Main Street, Anaconda, Deer Lodge County, MT

  2. DETAIL OF CORNICE MOULDING WITH RAM'S HEAD MOTIF. EIGHT SHADES ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    DETAIL OF CORNICE MOULDING WITH RAM'S HEAD MOTIF. EIGHT SHADES OF GOLD LEAF AND BURNISHED GOLD LEAF WERE USED FOR THE INTERIOR FINISHES. - Anaconda Historic District, Washoe Theater, 305 Main Street, Anaconda, Deer Lodge County, MT

  3. The building blocks and motifs of RNA architecture

    PubMed Central

    Leontis, Neocles B; Lescoute, Aurelie; Westhof, Eric

    2010-01-01

    RNA motifs can be defined broadly as recurrent structural elements containing multiple intramolecular RNA–RNA interactions, as observed in atomic-resolution RNA structures. They constitute the modular building blocks of RNA architecture, which is organized hierarchically. Recent work has focused on analyzing RNA backbone conformations to identify, define and search for new instances of recurrent motifs in X-ray structures. One current view asserts that recurrent RNA strand segments with characteristic backbone configurations qualify as independent motifs. Other considerations indicate that, to characterize modular motifs, one must take into account the larger structural context of such strand segments. This follows the biologically relevant motivation, which is to identify RNA structural characteristics that are subject to sequence constraints and that thus relate RNA architectures to sequences. PMID:16713707

  4. Network motifs emerge from interconnections that favour stability

    NASA Astrophysics Data System (ADS)

    Angulo, Marco Tulio; Liu, Yang-Yu; Slotine, Jean-Jacques

    2015-10-01

    The microscopic principles organizing dynamic units in complex networks--from proteins to power generators--can be understood in terms of network `motifs’: small interconnection patterns that appear much more frequently in real networks than expected in random networks. When considered as small subgraphs isolated from a large network, these motifs are more robust to parameter variations, easier to synchronize than other possible subgraphs, and can provide specific functionalities. But one can isolate these subgraphs only by assuming, for example, a significant separation of timescales, and the origin of network motifs and their functionalities when embedded in larger networks remain unclear. Here we show that most motifs emerge from interconnection patterns that best exploit the intrinsic stability characteristics at different scales of interconnection, from simple nodes to whole modules. This functionality suggests an efficient mechanism to stably build complex systems by recursively interconnecting nodes and modules as motifs. We present direct evidence of this mechanism in several biological networks.

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

    PubMed Central

    2012-01-01

    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 approaches. Some of these

  6. Robust and Adaptive MicroRNA-Mediated Incoherent Feedforward Motifs

    NASA Astrophysics Data System (ADS)

    Xu, Feng-Dan; Liu, Zeng-Rong; Zhang, Zhi-Yong; Shen, Jian-Wei

    2009-02-01

    We integrate transcriptional and post-transcriptional regulation into microRNA-mediated incoherent feedforward motifs and analyse their dynamical behaviour and functions. The analysis show that the behaviour of the system is almost uninfluenced by the varying input in certain ranges and by introducing of delay and noise. The results indicate that microRNA-mediated incoherent feedforward motifs greatly enhance the robustness of gene regulation.

  7. Network motif-based method for identifying coronary artery disease

    PubMed Central

    LI, YIN; CONG, YAN; ZHAO, YUN

    2016-01-01

    The present study aimed to develop a more efficient method for identifying coronary artery disease (CAD) than the conventional method using individual differentially expressed genes (DEGs). GSE42148 gene microarray data were downloaded, preprocessed and screened for DEGs. Additionally, based on transcriptional regulation data obtained from ENCODE database and protein-protein interaction data from the HPRD, the common genes were downloaded and compared with genes annotated from gene microarrays to screen additional common genes in order to construct an integrated regulation network. FANMOD was then used to detect significant three-gene network motifs. Subsequently, GlobalAncova was used to screen differential three-gene network motifs between the CAD group and the normal control data from GSE42148. Genes involved in the differential network motifs were then subjected to functional annotation and pathway enrichment analysis. Finally, clustering analysis of the CAD and control samples was performed based on individual DEGs and the top 20 network motifs identified. In total, 9,008 significant three-node network motifs were detected from the integrated regulation network; these were categorized into 22 interaction modes, each containing a minimum of one transcription factor. Subsequently, 1,132 differential network motifs involving 697 genes were screened between the CAD and control group. The 697 genes were enriched in 154 gene ontology terms, including 119 biological processes, and 14 KEGG pathways. Identifying patients with CAD based on the top 20 network motifs provided increased accuracy compared with the conventional method based on individual DEGs. The results of the present study indicate that the network motif-based method is more efficient and accurate for identifying CAD patients than the conventional method based on individual DEGs. PMID:27347046

  8. Diagnose Test-Taker's Profile in Terms of Core Profile Patterns: Principal Component (PC) vs. Profile Analysis via MDS (PAMS) Approaches.

    ERIC Educational Resources Information Center

    Kim, Se-Kang; Davison, Mark L.

    A study was conducted to examine how principal components analysis (PCA) and Profile Analysis via Multidimensional Scaling (PAMS) can be used to diagnose individuals observed score profiles in terms of core profile patterns identified by each method. The standardization sample from the Wechsler Intelligence Scale for Children, Third Edition…

  9. Time domain zero-padding based adaptive-PAM signal transmission with high spectral efficiency in IMDD optical communication system

    NASA Astrophysics Data System (ADS)

    Zhang, Fangliu; He, Jing; Deng, Rui; Cheng, Yun; Xiao, Minlei; Chen, Lin

    2016-08-01

    In this paper, an adaptive pulse amplitude modulation (APAM) scheme is proposed and experimentally demonstrated in the intensity-modulation and direct-detection (IMDD) optical communications system. In the proposed scheme, the channel is divided into two sub-channels, and different PAM mapping can be chosen for different sub-channel according to the fading conditions. In addition, the 20-km standard single mode fiber (SSMF) transmission of 24 Gbit/s 16/4-APAM signal with the spectral efficiency (SE) up to 6 bit/s/Hz is experimentally demonstrated. The experiment results show that the bit error rate (BER) of the 16/4-APAM signal can be achieved less than 2.4e-2.

  10. Transcriptional Network Growing Models Using Motif-Based Preferential Attachment

    PubMed Central

    Abdelzaher, Ahmed F.; Al-Musawi, Ahmad F.; Ghosh, Preetam; Mayo, Michael L.; Perkins, Edward J.

    2015-01-01

    Understanding relationships between architectural properties of gene-regulatory networks (GRNs) has been one of the major goals in systems biology and bioinformatics, as it can provide insights into, e.g., disease dynamics and drug development. Such GRNs are characterized by their scale-free degree distributions and existence of network motifs – i.e., small-node subgraphs that occur more abundantly in GRNs than expected from chance alone. Because these transcriptional modules represent “building blocks” of complex networks and exhibit a wide range of functional and dynamical properties, they may contribute to the remarkable robustness and dynamical stability associated with the whole of GRNs. Here, we developed network-construction models to better understand this relationship, which produce randomized GRNs by using transcriptional motifs as the fundamental growth unit in contrast to other methods that construct similar networks on a node-by-node basis. Because this model produces networks with a prescribed lower bound on the number of choice transcriptional motifs (e.g., downlinks, feed-forward loops), its fidelity to the motif distributions observed in model organisms represents an improvement over existing methods, which we validated by contrasting their resultant motif and degree distributions against existing network-growth models and data from the model organism of the bacterium Escherichia coli. These models may therefore serve as novel testbeds for further elucidating relationships between the topology of transcriptional motifs and network-wide dynamical properties. PMID:26528473

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

    PubMed

    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. PMID:26886735

  12. Finding specific RNA motifs: Function in a zeptomole world?

    PubMed Central

    KNIGHT, ROB; YARUS, MICHAEL

    2003-01-01

    We have developed a new method for estimating the abundance of any modular (piecewise) RNA motif within a longer random region. We have used this method to estimate the size of the active motifs available to modern SELEX experiments (picomoles of unique sequences) and to a plausible RNA World (zeptomoles of unique sequences: 1 zmole = 602 sequences). Unexpectedly, activities such as specific isoleucine binding are almost certainly present in zeptomoles of molecules, and even ribozymes such as self-cleavage motifs may appear (depending on assumptions about the minimal structures). The number of specified nucleotides is not the only important determinant of a motif’s rarity: The number of modules into which it is divided, and the details of this division, are also crucial. We propose three maxims for easily isolated motifs: the Maxim of Minimization, the Maxim of Multiplicity, and the Maxim of the Median. These maxims together state that selected motifs should be small and composed of as many separate, equally sized modules as possible. For evenly divided motifs with four modules, the largest accessible activity in picomole scale (1–1000 pmole) pools of length 100 is about 34 nucleotides; while for zeptomole scale (1–1000 zmole) pools it is about 20 specific nucleotides (50% probability of occurrence). This latter figure includes some ribozymes and aptamers. Consequently, an RNA metabolism apparently could have begun with only zeptomoles of RNA molecules. PMID:12554865

  13. Motif for controllable toggle switch in gene regulatory networks

    NASA Astrophysics Data System (ADS)

    Zhao, Chen; Bin, Ao; Ye, Weiming; Fan, Ying; Di, Zengru

    2015-02-01

    Toggle switch as a common phenomenon in gene regulatory networks has been recognized important for biological functions. Despite much effort dedicated to understanding the toggle switch and designing synthetic biology circuit to achieve the biological function, we still lack a comprehensive understanding of the intrinsic dynamics behind such phenomenon and the minimum structure that is imperative for producing toggle switch. In this paper, we discover a minimum structure, a motif that enables a controllable toggle switch. In particular, the motif consists of a transformative double negative feedback loop (DNFL) that is regulated by an additional driver node. By enumerating all possible regulatory configurations from the driver node, we identify two types of motifs associated with the toggle switch that is captured by the existence of bistable states. The toggle switch is controllable in the sense that the gap between the bistable states is adjustable as determined by the regulatory strength from the driver nodes. We test the effect of the motifs in self-oscillating gene regulatory network (SON) with respect to the interplay between the motifs and the other genes, and find that the switching dynamics of the whole network can be successfully controlled insofar as the network contains a single motif. Our findings are important to uncover the underlying nonlinear dynamics of controllable toggle switch and can have implications in devising biology circuit in the field of synthetic biology.

  14. Heparin-Binding Motifs and Biofilm Formation by Candida albicans

    PubMed Central

    Green, Julianne V.; Orsborn, Kris I.; Zhang, Minlu; Tan, Queenie K. G.; Greis, Kenneth D.; Porollo, Alexey; Andes, David R.; Long Lu, Jason; Hostetter, Margaret K.

    2013-01-01

    Candida albicans is a leading pathogen in infections of central venous catheters, which are frequently infused with heparin. Binding of C. albicans to medically relevant concentrations of soluble and plate-bound heparin was demonstrable by confocal microscopy and enzyme-linked immunosorbent assay (ELISA). A sequence-based search identified 34 C. albicans surface proteins containing ≥1 match to linear heparin-binding motifs. The virulence factor Int1 contained the most putative heparin-binding motifs (n = 5); peptides encompassing 2 of 5 motifs bound to heparin-Sepharose. Alanine substitution of lysine residues K805/K806 in 804QKKHQIHK811 (motif 1 of Int1) markedly attenuated biofilm formation in central venous catheters in rats, whereas alanine substitution of K1595/R1596 in 1593FKKRFFKL1600 (motif 4 of Int1) did not impair biofilm formation. Affinity-purified immunoglobulin G (IgG) recognizing motif 1 abolished biofilm formation in central venous catheters; preimmune IgG had no effect. After heparin treatment of C. albicans, soluble peptides from multiple C. albicans surface proteins were detected, such as Eno1, Pgk1, Tdh3, and Ssa1/2 but not Int1, suggesting that heparin changes candidal surface structures and may modify some antigens critical for immune recognition. These studies define a new mechanism of biofilm formation for C. albicans and a novel strategy for inhibiting catheter-associated biofilms. PMID:23904295

  15. Directed network motifs in Alzheimer's disease and mild cognitive impairment.

    PubMed

    Friedman, Eric J; Young, Karl; Tremper, Graham; Liang, Jason; Landsberg, Adam S; Schuff, Norbert

    2015-01-01

    Directed network motifs are the building blocks of complex networks, such as human brain networks, and capture deep connectivity information that is not contained in standard network measures. In this paper we present the first application of directed network motifs in vivo to human brain networks, utilizing recently developed directed progression networks which are built upon rates of cortical thickness changes between brain regions. This is in contrast to previous studies which have relied on simulations and in vitro analysis of non-human brains. We show that frequencies of specific directed network motifs can be used to distinguish between patients with Alzheimer's disease (AD) and normal control (NC) subjects. Especially interesting from a clinical standpoint, these motif frequencies can also distinguish between subjects with mild cognitive impairment who remained stable over three years (MCI) and those who converted to AD (CONV). Furthermore, we find that the entropy of the distribution of directed network motifs increased from MCI to CONV to AD, implying that the distribution of pathology is more structured in MCI but becomes less so as it progresses to CONV and further to AD. Thus, directed network motifs frequencies and distributional properties provide new insights into the progression of Alzheimer's disease as well as new imaging markers for distinguishing between normal controls, stable mild cognitive impairment, MCI converters and Alzheimer's disease. PMID:25879535

  16. cWINNOWER Algorithm for Finding Fuzzy DNA Motifs

    NASA Technical Reports Server (NTRS)

    Liang, Shoudan

    2003-01-01

    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 multiple mutated copies of the motif (i.e., the signals) are present in the DNA sequence in sufficient abundance. 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 number of detectable motifs 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 = 12000 for (l,d) = (15,4).

  17. Ius Chasma Tributary Valleys and Adjacent Plains

    NASA Technical Reports Server (NTRS)

    2006-01-01

    This image covers valley tributaries of Ius Chasma, as well as the plains adjacent to the valleys. Ius Chasma is one of several canyons that make up the Valles Marineris canyon system. Valles Marineris likely formed by extension associated with the growth of the large volcanoes and topographic high of Tharsis to the northwest. As the ground was pulled apart, large and deep gaps resulted in the valleys seen in the top and bottom of this HiRISE image. Ice that was once in the ground could have also melted to create additional removal of material in the formation of the valleys. HiRISE is able to see the rocks along the walls of both these valleys and also impact craters in the image. Rock layers that appear lower down in elevation appear rougher and are shedding boulders. Near the top of the walls and also seen in patches along the smooth plains are brighter layers. These brighter layers are not shedding boulders so they must represent a different kind of rock formed in a different kind of environment than those further down the walls. Because they are highest in elevation, the bright layers are youngest in age. HiRISE is able to see dozens of the bright layers, which are perhaps only a meter in thickness. Darker sand dunes and ripples cover most of the plains and fill the floors of impact craters.

    Image PSP_001351_1715 was taken by the High Resolution Imaging Science Experiment (HiRISE) camera onboard the Mars Reconnaissance Orbiter spacecraft on November 9, 2006. The complete image is centered at -8.3 degrees latitude, 275.4 degrees East longitude. The range to the target site was 254.3 km (158.9 miles). At this distance the image scale ranges from 25.4 cm/pixel (with 1 x 1 binning) to 101.8 cm/pixel (with 4 x 4 binning). The image shown here has been map-projected to 25 cm/pixel and north is up. The image was taken at a local Mars time of 3:32 PM and the scene is illuminated from the west with a solar incidence angle of 59 degrees, thus the sun was about

  18. Influence of Nutrient Stress on the Relationships between PAM Measurements and Carbon Incorporation in Four Phytoplankton Species

    PubMed Central

    Napoléon, Camille; Raimbault, Virginie; Claquin, Pascal

    2013-01-01

    Two methods of measuring primary production, modulated fluorimetry (PAM) and the traditional carbon incorporation method (13C), were compared in four phytoplankton species, two diatoms (Pseudo-nitzschia pungens and Asterionellopsis glacialis), and two dinoflagellates (Heterocapsa sp and Karenia mikimotoï), under N (nitrogen), P (phosphorus) and Si (silicon) limited semi-continuous culture. N and Si-limited cultures showed relatively high quantum efficiency of the PSII (Fv/Fm) values, confirming that Fv/Fm is not a good proxy for nutrient stress in balanced systems, whereas P limitation had a drastic effect on many physiological parameters. In all species, the physiological capacity of phytoplankton cells to acclimate to nutrient limitations led to changes in the cellular biochemical composition and the structure of the photosynthetic apparatus. The observed physiological responses were species and nutrient specific. The values of the chlorophyll-specific absorption cross section (a*) increased with nutrient limitation due to package effect, while the carbon/Chl a ratio was higher under N and P limitations. In diatoms, Si limitation did not affect photosynthesis confirming the uncoupling between Si and carbon metabolisms. In all four species and under all treatments, significant relationships were found between photosynthetic activities, ETRChl (electron transport rate) and PChl (carbon fixation rate) estimated using PAM measurements and 13C incorporation, showing that the fluorescence technique can reliably be used to estimate carbon fixation by phytoplankton. The relationship between ETRChl and PChl can be described by the shape and the slope of the curve (ΦC.e). Linear relationships were found for dinoflagellates and P. pungens under all treatments. A decrease in ΦC.e was observed under N and P limitation probably due to structural damage to the photosynthetic apparatus. A. glacialis showed a logarithmic relationship in N and P limited conditions, due to the

  19. Application Evaluation of Air-Sparging and Aerobic Bioremediation in PAM(Physical Aquifer Model) with Advanced and Integrated Module

    NASA Astrophysics Data System (ADS)

    Hong, U.; Ko, J.; Park, S.; Kim, Y.; Kwon, S.; Ha, J.; Lim, J.; Han, K.

    2010-12-01

    It is generally difficult for a single process to remediate contaminated soil and groundwater contaminated with various organic compounds such as total petroleum hydrocarbon (TPH), benzene, toluene, ethylbenzene, xylene (BTEX), chlorinated aliphatic hydrocarbons (CAHs) because those contaminants show different chemical properties in two phases (e.g. soil and groundwater). Therefore, it is necessary to design an in-situ remediation system which can remove various contaminants simultaneously. For the purpose, we constructed integrated well module which can apply several remediation process such as air sparging, soil vapor extraction, and bioventing. The advanced integrated module consisted of three main parts such as head, body, and end cap. First of all, head part has three 3.6-cm-diameter stainless lines and can simultaneously inject air or extract NAPL, respectively. Secondly, body part has two 10-cm-height screen intervals with 100-mesh stainless inserts for unsaturated and smear zone. Lastly, we constructed three different sizes of end caps for injection and extraction from a saturated zone. We assumed that the integrated module can play bioremediation, air sparging, cometabolic sparging, chemical oxidation. In this study, we examined application of air sparing and aerobic bioremediation of toluene in Physical Aquifer Model (PAM) with an integrated well module. During air sparging experiments, toluene concentration decreased by injection of air. In addition, we accomplished bioremediation experiment to evaluate removal of toluene by indigenous microbes in PAM with continuous air injection. From the two experiments result, we confirmed that air sparging and aerobic bioremediation processes can be simultaneously carried out by an intergrated well module.

  20. Activation of superoxide formation and lysozyme release in human neutrophils by the synthetic lipopeptide Pam3Cys-Ser-(Lys)4. Involvement of guanine-nucleotide-binding proteins and synergism with chemotactic peptides.

    PubMed Central

    Seifert, R; Schultz, G; Richter-Freund, M; Metzger, J; Wiesmüller, K H; Jung, G; Bessler, W G; Hauschildt, S

    1990-01-01

    Upon exposure to the bacterial chemotactic peptide fMet-Leu-Phe, human neutrophils release lysozyme and generate superoxide anions (O2.-). The synthetic lipoamino acid N-palmitoyl-S-[2,3-bis(palmitoyloxy)-(2RS)-propyl]-(R)-cysteine (Pam3Cys), which is derived from the N-terminus of bacterial lipoprotein, when attached to Ser-(Lys)4 [giving Pam3Cys-Ser-(Lys)4], activated O2.- formation and lysozyme release in human neutrophils with an effectiveness amounting to about 15% of that of fMet-Leu-Phe. Palmitic acid, muramyl dipeptide, lipopolysaccharide and the lipopeptides Pam3Cys-Ala-Gly, Pam3Cys-Ser-Gly, Pam3Cys-Ser, Pam3Cys-OMe and Pam3Cys-OH did not activate O2.- formation. Pertussis toxin, which ADP-ribosylates guanine-nucleotide-binding proteins (G-proteins) and functionally uncouples formyl peptide receptors from G-proteins, prevented activation of O2.- formation by fMet-Leu-Phe and inhibited Pam3Cys-Ser-(Lys)4-induced O2.- formation by 85%. Lipopeptide-induced exocytosis was pertussis-toxin-insensitive. O2.- formation induced by Pam3Cys-Ser-(Lys)4 and fMet-Leu-Phe was enhanced by cytochalasin B, by a phorbol ester and by a diacylglycerol kinase inhibitor. Addition of activators of adenylate cyclase and removal of extracellular Ca2+ inhibited O2.- formation by fMet-Leu-Phe and Pam3Cys-Ser-(Lys)4 to different extents. Pam3Cys-Ser-(Lys)4 synergistically enhanced fMet-Leu-Phe-induced O2.- formation and primed neutrophils to respond to the chemotactic peptide at non-stimulatory concentrations. Our data suggest the following. (1) Pam3Cys-Ser-(Lys)4 activates neutrophils through G-proteins, involving pertussis-toxin-sensitive and -insensitive processes. (2) The signal transduction pathways activated by fMet-Leu-Phe and Pam3Cys-Ser-(Lys)4 are similar but not identical. (3) In inflammatory processes, bacterial lipoproteins and chemotactic peptides may interact synergistically to activate O2.- formation, leading to enhanced bactericidal activity. PMID:2160237

  1. Motif types, motif locations and base composition patterns around the RNA polyadenylation site in microorganisms, plants and animals

    PubMed Central

    2014-01-01

    Background The polyadenylation of RNA is critical for gene functioning, but the conserved sequence motifs (often called signal or signature motifs), motif locations and abundances, and base composition patterns around mRNA polyadenylation [poly(A)] sites are still uncharacterized in most species. The evolutionary tendency for poly(A) site selection is still largely unknown. Results We analyzed the poly(A) site regions of 31 species or phyla. Different groups of species showed different poly(A) signal motifs: UUACUU at the poly(A) site in the parasite Trypanosoma cruzi; UGUAAC (approximately 13 bases upstream of the site) in the alga Chlamydomonas reinhardtii; UGUUUG (or UGUUUGUU) at mainly the fourth base downstream of the poly(A) site in the parasite Blastocystis hominis; and AAUAAA at approximately 16 bases and approximately 19 bases upstream of the poly(A) site in animals and plants, respectively. Polyadenylation signal motifs are usually several hundred times more abundant around poly(A) sites than in whole genomes. These predominant motifs usually had very specific locations, whether upstream of, at, or downstream of poly(A) sites, depending on the species or phylum. The poly(A) site was usually an adenosine (A) in all analyzed species except for B. hominis, and there was weak A predominance in C. reinhardtii. Fungi, animals, plants, and the protist Phytophthora infestans shared a general base abundance pattern (or base composition pattern) of “U-rich—A-rich—U-rich—Poly(A) site—U-rich regions”, or U-A-U-A-U for short, with some variation for each kingdom or subkingdom. Conclusion This study identified the poly(A) signal motifs, motif locations, and base composition patterns around mRNA poly(A) sites in protists, fungi, plants, and animals and provided insight into poly(A) site evolution. PMID:25052519

  2. View of north side from exterior stairs of adjacent building, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    View of north side from exterior stairs of adjacent building, bottom cut off by fringed buildings, view facing south-southwest - U.S. Naval Base, Pearl Harbor, Industrial X-Ray Building, Off Sixth Street, adjacent to and south of Facility No. 11, Pearl City, Honolulu County, HI

  3. Learning Non-Adjacent Regularities at Age 0 ; 7

    ERIC Educational Resources Information Center

    Gervain, Judit; Werker, Janet F.

    2013-01-01

    One important mechanism suggested to underlie the acquisition of grammar is rule learning. Indeed, infants aged 0 ; 7 are able to learn rules based on simple identity relations (adjacent repetitions, ABB: "wo fe fe" and non-adjacent repetitions, ABA: "wo fe wo", respectively; Marcus et al., 1999). One unexplored issue is…

  4. Delayed Acquisition of Non-Adjacent Vocalic Distributional Regularities

    ERIC Educational Resources Information Center

    Gonzalez-Gomez, Nayeli; Nazzi, Thierry

    2016-01-01

    The ability to compute non-adjacent regularities is key in the acquisition of a new language. In the domain of phonology/phonotactics, sensitivity to non-adjacent regularities between consonants has been found to appear between 7 and 10 months. The present study focuses on the emergence of a posterior-anterior (PA) bias, a regularity involving two…

  5. A comprehensive analysis of the La-motif protein superfamily

    PubMed Central

    Bousquet-Antonelli, Cécile; Deragon, Jean-Marc

    2009-01-01

    The extremely well-conserved La motif (LAM), in synergy with the immediately following RNA recognition motif (RRM), allows direct binding of the (genuine) La autoantigen to RNA polymerase III primary transcripts. This motif is not only found on La homologs, but also on La-related proteins (LARPs) of unrelated function. LARPs are widely found amongst eukaryotes and, although poorly characterized, appear to be RNA-binding proteins fulfilling crucial cellular functions. We searched the fully sequenced genomes of 83 eukaryotic species scattered along the tree of life for the presence of LAM-containing proteins. We observed that these proteins are absent from archaea and present in all eukaryotes (except protists from the Plasmodium genus), strongly suggesting that the LAM is an ancestral motif that emerged early after the archaea-eukarya radiation. A complete evolutionary and structural analysis of these proteins resulted in their classification into five families: the genuine La homologs and four LARP families. Unexpectedly, in each family a conserved domain representing either a classical RRM or an RRM-like motif immediately follows the LAM of most proteins. An evolutionary analysis of the LAM-RRM/RRM-L regions shows that these motifs co-evolved and should be used as a single entity to define the functional region of interaction of LARPs with their substrates. We also found two extremely well conserved motifs, named LSA and DM15, shared by LARP6 and LARP1 family members, respectively. We suggest that members of the same family are functional homologs and/or share a common molecular mode of action on different RNA baits. PMID:19299548

  6. HMM-based prediction for protein structural motifs' two local properties: solvent accessibility and backbone torsion angles.

    PubMed

    Yu, Jianyong; Xiang, Leijun; Hong, Jiang; Zhang, Weidong

    2013-02-01

    Protein structure prediction is often assisted by predicting one-dimensional structural properties including relative solvent accessibility (RSA) surface and backbone torsion angles (BTA) of residues, and these two properties are continuously varying variables because proteins can move freely in a three-dimensional space. Instead of subdividing them into a few arbitrarily defined states that many popular approaches used, this paper proposes an integrated system for realvalue prediction of protein structural motifs' two local properties, based on the modified Hidden Markov Model that we previously presented. The model was used to capture the relevance of RSA and the dependency of BTA between adjacent residues along the local protein chain in motifs with definite probabilities. These two properties were predicted according to their own probability distribution. The method was applied to a protein fragment library. For nine different classes of motifs, real values of RSA were predicted with mean absolute error (MAE) of 0.122-0.175 and Pearson's correlation coefficient (PCC) of 0.623-0.714 between predicted and actual RSA. Meanwhile, real values of BTA were obtained with MAE of 8.5⁰-29.4⁰ for Φ angles, 11.2⁰-38.5⁰ for ψ angles and PCC of 0.601-0.716 for Φ, 0.597-0.713 for ψ. The results were compared with well-known Real-SPINE Server, and indicate the proposed method may at least serve as the foundation to obtain better local properties from structural motifs for protein structure prediction. PMID:22894152

  7. The Eps1p Protein Disulfide Isomerase Conserves Classic Thioredoxin Superfamily Amino Acid Motifs but Not Their Functional Geometries

    PubMed Central

    Biran, Shai; Gat, Yair; Fass, Deborah

    2014-01-01

    The widespread thioredoxin superfamily enzymes typically share the following features: a characteristic α-β fold, the presence of a Cys-X-X-Cys (or Cys-X-X-Ser) redox-active motif, and a proline in the cis configuration abutting the redox-active site in the tertiary structure. The Cys-X-X-Cys motif is at the solvent-exposed amino terminus of an α-helix, allowing the first cysteine to engage in nucleophilic attack on substrates, or substrates to attack the Cys-X-X-Cys disulfide, depending on whether the enzyme functions to reduce, isomerize, or oxidize its targets. We report here the X-ray crystal structure of an enzyme that breaks many of our assumptions regarding the sequence-structure relationship of thioredoxin superfamily proteins. The yeast Protein Disulfide Isomerase family member Eps1p has Cys-X-X-Cys motifs and proline residues at the appropriate primary structural positions in its first two predicted thioredoxin-fold domains. However, crystal structures show that the Cys-X-X-Cys of the second domain is buried and that the adjacent proline is in the trans, rather than the cis isomer. In these configurations, neither the “active-site” disulfide nor the backbone carbonyl preceding the proline is available to interact with substrate. The Eps1p structures thus expand the documented diversity of the PDI oxidoreductase family and demonstrate that conserved sequence motifs in common folds do not guarantee structural or functional conservation. PMID:25437863

  8. Upstream stimulatory factor activates the vasopressin promoter via multiple motifs, including a non-canonical E-box.

    PubMed Central

    Coulson, Judy M; Edgson, Jodie L; Marshall-Jones, Zoe V; Mulgrew, Robert; Quinn, John P; Woll, Penella J

    2003-01-01

    We have described previously a complex E-box enhancer (-147) of the vasopressin promoter in small-cell lung cancer (SCLC) extracts [Coulson, Fiskerstrand, Woll and Quinn, (1999) Biochem. J. 344, 961-970]. Upstream stimulatory factor (USF) heterodimers were one of the complexes binding to this site in vitro. We now report that USF overexpression in non-SCLC (NSCLC) cells can functionally activate vasopressin promoter-driven reporters that are otherwise inactive in this type of lung cancer cell. Site-directed mutagenesis and electrophoretic mobility-shift analysis demonstrate that although the -147 E-box contributes, none of the previously predicted E-boxes (-147, -135, -34) wholly account for this USF-mediated activation in NSCLC. 5' Deletion showed the key promoter region as -52 to +42; however, USF-2 binding was not reliant on the -34 E-box, but on a novel adjacent CACGGG non-canonical E-box at -42 (motif E). This mediated USF binding in both SCLC and USF-2-transfected NSCLC cells. Mutation of motif E or the non-canonical TATA box abolished activity, implying both are required for transcriptional initiation on overexpression of USF-2. Co-transfected dominant negative USF confirmed that binding was required through motif E for function, but that the classical activation domain of USF was not essential. USF-2 bound motif E with 10-fold lower affinity than the -147 E-box. In NSCLC, endogenous USF-2 expression is low, and this basal level appears to be insufficient to activate transcription of arginine vasopressin (AVP). In summary, we have demonstrated a novel mechanism for USF activation, which contributes to differential vasopressin expression in lung cancer. PMID:12403649

  9. Discovering Motifs in Ranked Lists of DNA Sequences

    PubMed Central

    Eden, Eran; Lipson, Doron; Yogev, Sivan; Yakhini, Zohar

    2007-01-01

    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. Overall

  10. Mutations in the highly conserved GGQ motif of class 1 polypeptide release factors abolish ability of human eRF1 to trigger peptidyl-tRNA hydrolysis.

    PubMed Central

    Frolova, L Y; Tsivkovskii, R Y; Sivolobova, G F; Oparina, N Y; Serpinsky, O I; Blinov, V M; Tatkov, S I; Kisselev, L L

    1999-01-01

    Although the primary structures of class 1 polypeptide release factors (RF1 and RF2 in prokaryotes, eRF1 in eukaryotes) are known, the molecular basis by which they function in translational termination remains obscure. Because all class 1 RFs promote a stop-codon-dependent and ribosome-dependent hydrolysis of peptidyl-tRNAs, one may anticipate that this common function relies on a common structural motif(s). We have compared amino acid sequences of the available class 1 RFs and found a novel, common, unique, and strictly conserved GGQ motif that should be in a loop (coil) conformation as deduced by programs predicting protein secondary structure. Site-directed mutagenesis of the human eRF1 as a representative of class 1 RFs shows that substitution of both glycyl residues in this motif, G183 and G184, causes complete inactivation of the protein as a release factor toward all three stop codons, whereas two adjacent amino acid residues, G181 and R182, are functionally nonessential. Inactive human eRF1 mutants compete in release assays with wild-type eRF1 and strongly inhibit their release activity. Mutations of the glycyl residues in this motif do not affect another function, the ability of eRF1 together with the ribosome to induce GTPase activity of human eRF3, a class 2 RF. We assume that the novel highly conserved GGQ motif is implicated directly or indirectly in the activity of class 1 RFs in translation termination. PMID:10445876

  11. Interconnected Network Motifs Control Podocyte Morphology and Kidney Function

    PubMed Central

    Azeloglu, Evren U.; Hardy, Simon V.; Eungdamrong, Narat John; Chen, Yibang; Jayaraman, Gomathi; Chuang, Peter Y.; Fang, Wei; Xiong, Huabao; Neves, Susana R.; Jain, Mohit R.; Li, Hong; Ma’ayan, Avi; Gordon, Ronald E.; He, John Cijiang; Iyengar, Ravi

    2014-01-01

    Podocytes are kidney cells with specialized morphology that is required for glomerular filtration. Diseases, such as diabetes, or drug exposure that causes disruption of the podocyte foot process morphology results in kidney pathophysiology. Proteomic analysis of glomeruli isolated from rats with puromycin-induced kidney disease and control rats indicated that protein kinase A (PKA), which is activated by adenosine 3′,5′-monophosphate (cAMP), is a key regulator of podocyte morphology and function. In podocytes, cAMP signaling activates cAMP response element–binding protein (CREB) to enhance expression of the gene encoding a differentiation marker, synaptopodin, a protein that associates with actin and promotes its bundling. We constructed and experimentally verified a β-adrenergic receptor–driven network with multiple feedback and feedforward motifs that controls CREB activity. To determine how the motifs interacted to regulate gene expression, we mapped multicompartment dynamical models, including information about protein subcellular localization, onto the network topology using Petri net formalisms. These computational analyses indicated that the juxtaposition of multiple feedback and feedforward motifs enabled the prolonged CREB activation necessary for synaptopodin expression and actin bundling. Drug-induced modulation of these motifs in diseased rats led to recovery of normal morphology and physiological function in vivo. Thus, analysis of regulatory motifs using network dynamics can provide insights into pathophysiology that enable predictions for drug intervention strategies to treat kidney disease. PMID:24497609

  12. BC1 RNA motifs required for dendritic transport in vivo

    PubMed Central

    Robeck, Thomas; Skryabin, Boris V.; Rozhdestvensky, Timofey S.; Skryabin, Anastasiya B.; Brosius, Jürgen

    2016-01-01

    BC1 RNA is a small brain specific non-protein coding RNA. It is transported from the cell body into dendrites where it is involved in the fine-tuning translational control. Due to its compactness and established secondary structure, BC1 RNA is an ideal model for investigating the motifs necessary for dendritic localization. Previously, microinjection of in vitro transcribed BC1 RNA mutants into the soma of cultured primary neurons suggested the importance of RNA motifs for dendritic targeting. These ex vivo experiments identified a single bulged nucleotide (U22) and a putative K-turn (GA motif) structure required for dendritic localization or distal transport, respectively. We generated six transgenic mouse lines (three founders each) containing neuronally expressing BC1 RNA variants on a BC1 RNA knockout mouse background. In contrast to ex vivo data, we did not find indications of reduction or abolition of dendritic BC1 RNA localization in the mutants devoid of the GA motif or the bulged nucleotide. We confirmed the ex vivo data, which showed that the triloop terminal sequence had no consequence on dendritic transport. Interestingly, changing the triloop supporting structure completely abolished dendritic localization of BC1 RNA. We propose a novel RNA motif important for dendritic transport in vivo. PMID:27350115

  13. MALISAM: a database of structurally analogous motifs in proteins.

    PubMed

    Cheng, Hua; Kim, Bong-Hyun; Grishin, Nick V

    2008-01-01

    MALISAM (manual alignments for structurally analogous motifs) represents the first database containing pairs of structural analogs and their alignments. To find reliable analogs, we developed an approach based on three ideas. First, an insertion together with a part of the evolutionary core of one domain family (a hybrid motif) is analogous to a similar motif contained within the core of another domain family. Second, a motif at an interface, formed by secondary structural elements (SSEs) contributed by two or more domains or subunits contacting along that interface, is analogous to a similar motif present in the core of a single domain. Third, an artificial protein obtained through selection from random peptides or in sequence design experiments not biased by sequences of a particular homologous family, is analogous to a structurally similar natural protein. Each analogous pair is superimposed and aligned manually, as well as by several commonly used programs. Applications of this database may range from protein evolution studies, e.g. development of remote homology inference tools and discriminators between homologs and analogs, to protein-folding research, since in the absence of evolutionary reasons, similarity between proteins is caused by structural and folding constraints. The database is publicly available at http://prodata.swmed.edu/malisam. PMID:17855399

  14. DynaMIT: the dynamic motif integration toolkit

    PubMed Central

    Dassi, Erik; Quattrone, Alessandro

    2016-01-01

    De-novo motif search is a frequently applied bioinformatics procedure to identify and prioritize recurrent elements in sequences sets for biological investigation, such as the ones derived from high-throughput differential expression experiments. Several algorithms have been developed to perform motif search, employing widely different approaches and often giving divergent results. In order to maximize the power of these investigations and ultimately be able to draft solid biological hypotheses, there is the need for applying multiple tools on the same sequences and merge the obtained results. However, motif reporting formats and statistical evaluation methods currently make such an integration task difficult to perform and mostly restricted to specific scenarios. We thus introduce here the Dynamic Motif Integration Toolkit (DynaMIT), an extremely flexible platform allowing to identify motifs employing multiple algorithms, integrate them by means of a user-selected strategy and visualize results in several ways; furthermore, the platform is user-extendible in all its aspects. DynaMIT is freely available at http://cibioltg.bitbucket.org. PMID:26253738

  15. Mining tertiary structural motifs for assessment of designability.

    PubMed

    Zhang, Jian; Grigoryan, Gevorg

    2013-01-01

    The observation of a limited secondary-structural alphabet in native proteins, with significant sequence preferences, has profoundly influenced the fields of protein design and structure prediction (Simons, Kooperberg, Huang, & Baker, 1997; Verschueren et al., 2011). In the era of structural genomics, as the size of the structural dataset continues to grow rapidly, it is becoming possible to extend this analysis to tertiary structural motifs and their sequences. For a hypothetical tertiary motif, the rate of its utilization in natural proteins may be used to assess its designability-the ease with which the motif can be realized with natural amino acids. This requires a structural similarity search methodology, which rather than looking for global topological agreement (more appropriate for categorization of full proteins or domains), identifies detailed geometric matches. In this chapter, we introduce such a method, called MaDCaT, and demonstrate its use by assessing the designability landscapes of two tertiary structural motifs. We also show that such analysis can establish structure/sequence links by providing the sequence constraints necessary to encode designable motifs. As logical extension of their secondary-structure counterparts, tertiary structural preferences will likely prove extremely useful in de novo protein design and structure prediction. PMID:23422424

  16. BC1 RNA motifs required for dendritic transport in vivo.

    PubMed

    Robeck, Thomas; Skryabin, Boris V; Rozhdestvensky, Timofey S; Skryabin, Anastasiya B; Brosius, Jürgen

    2016-01-01

    BC1 RNA is a small brain specific non-protein coding RNA. It is transported from the cell body into dendrites where it is involved in the fine-tuning translational control. Due to its compactness and established secondary structure, BC1 RNA is an ideal model for investigating the motifs necessary for dendritic localization. Previously, microinjection of in vitro transcribed BC1 RNA mutants into the soma of cultured primary neurons suggested the importance of RNA motifs for dendritic targeting. These ex vivo experiments identified a single bulged nucleotide (U22) and a putative K-turn (GA motif) structure required for dendritic localization or distal transport, respectively. We generated six transgenic mouse lines (three founders each) containing neuronally expressing BC1 RNA variants on a BC1 RNA knockout mouse background. In contrast to ex vivo data, we did not find indications of reduction or abolition of dendritic BC1 RNA localization in the mutants devoid of the GA motif or the bulged nucleotide. We confirmed the ex vivo data, which showed that the triloop terminal sequence had no consequence on dendritic transport. Interestingly, changing the triloop supporting structure completely abolished dendritic localization of BC1 RNA. We propose a novel RNA motif important for dendritic transport in vivo. PMID:27350115

  17. cWINNOWER algorithm for finding fuzzy dna motifs

    NASA Technical Reports Server (NTRS)

    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.

  18. Adjacent Gene Pairing Plays a Role in the Coordinated Expression of Ribosome Biogenesis Genes MPP10 and YJR003C in Saccharomyces cerevisiae ▿

    PubMed Central

    Arnone, James T.; McAlear, Michael A.

    2011-01-01

    The rRNA and ribosome biogenesis (RRB) regulon from Saccharomyces cerevisiae contains some 200 genes, the expression of which is tightly regulated under changing cellular conditions. RRB gene promoters are enriched for the RRPE and PAC consensus motifs, and a significant fraction of RRB genes are found as adjacent gene pairs. A genetic analysis of the MPP10 promoter revealed that both the RRPE and PAC motifs are important for coordinated expression of MPP10 following heat shock, osmotic stress, and glucose replenishment. The association of the RRPE binding factor Stb3 with the MPP10 promoter was found to increase after glucose replenishment and to decrease following heat shock. Similarly, bulk histone H3 clearing and histone H4K12 acetylation levels at the MPP10 promoter were found to increase or decrease following glucose replenishment or heat shock, respectively. Interestingly, substitutions in the PAC and RRPE sequences at the MPP10 promoter were also found to impact the regulated expression of the adjacent RRB gene YJR003, whose promoter lies in the opposite orientation and some 3.8 kb away. Furthermore, the regulated expression of YJR003C could be disrupted by inserting a reporter cassette that increased its distance from MPP10. Given that a high incidence of gene pairing was also found within the ribosomal protein (RP) and RRB regulons across different yeast species, our results indicate that immediately adjacent positioning of genes can be functionally significant for their coregulated expression. PMID:21115740

  19. Thermoelastic response of thin metal films and their adjacent materials

    SciTech Connect

    Kang, S.; Yoon, Y.; Kim, J.; Kim, W.

    2013-01-14

    A pulsed laser beam applied to a thin metal film is capable of launching an acoustic wave due to thermal expansion. Heat transfer from the thin metal film to adjacent materials can also induce thermal expansion; thus, the properties of these adjacent materials (as well as the thin metal film) should be considered for a complete description of the thermoelastic response. Here, we show that adjacent materials with a small specific heat and large thermal expansion coefficient can generate an enhanced acoustic wave and we demonstrate a three-fold increase in the peak pressure of the generated acoustic wave on substitution of parylene for polydimethylsiloxane.

  20. Robustness to noise in synchronization of network motifs: Experimental results

    NASA Astrophysics Data System (ADS)

    Buscarino, Arturo; Fortuna, Luigi; Frasca, Mattia; Iachello, Marco; Pham, Viet-Thanh

    2012-12-01

    In this work, we experimentally investigate the robustness to noise of synchronization in all the four-nodes network motifs. The experimental setup consists of four Chua's circuits diffusively coupled in order to implement the six different undirected network motifs that can be obtained with four nodes. In this experimental setup, synchronization in the presence of noise injected in one of the network nodes is investigated and network motifs are compared in terms of the synchronization error obtained. The analysis has been then extended to some selected case studies of networks with five and six nodes. Numerical simulations have been also performed and results in agreement with experiments have been obtained. A correlation between node degree and robustness to noise has been found also in these networks.

  1. Identification of high-molecular-weight proteins with multiple EGF-like motifs by motif-trap screening.

    PubMed

    Nakayama, M; Nakajima, D; Nagase, T; Nomura, N; Seki, N; Ohara, O

    1998-07-01

    To identify large proteins with an EGF-like-motif in a systematic manner, we developed a computer-assisted method called motif-trap screening. The method exploits 5'-end single-pass sequence data obtained from a pool of cDNAs whose sizes exceed 5 kb. Using this screening procedure, we were able to identify five known and nine new genes for proteins with multiple EGF-like-motifs from 8000 redundant human brain cDNA clones. These new genes were found to encode a novel mammalian homologue of Drosophila fat protein, two seven-transmembrane proteins containing multiple cadherin and EGF-like motifs, two mammalian homologues of Drosophila slit protein, an unidentified LDL receptor-like protein, and three totally uncharacterized proteins. The organization of the domains in the proteins, together with their expression profiles and fine chromosomal locations, has indicated their biological significance, demonstrating that motif-trap screening is a powerful tool for the discovery of new genes that have been difficult to identify by conventional methods. PMID:9693030

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

    SciTech Connect

    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.

  3. Analysis of interactions between ribosomal proteins and RNA structural motifs

    PubMed Central

    2010-01-01

    Background One important goal of structural bioinformatics is to recognize and predict the interactions between protein binding sites and RNA. Recently, a comprehensive analysis of ribosomal proteins and their interactions with rRNA has been done. Interesting results emerged from the comparison of r-proteins within the small subunit in T. thermophilus and E. coli, supporting the idea of a core made by both RNA and proteins, conserved by evolution. Recent work showed also that ribosomal RNA is modularly composed. Motifs are generally single-stranded sequences of consecutive nucleotides (ssRNA) with characteristic folding. The role of these motifs in protein-RNA interactions has been so far only sparsely investigated. Results This work explores the role of RNA structural motifs in the interaction of proteins with ribosomal RNA (rRNA). We analyze composition, local geometries and conformation of interface regions involving motifs such as tetraloops, kink turns and single extruded nucleotides. We construct an interaction map of protein binding sites that allows us to identify the common types of shared 3-D physicochemical binding patterns for tetraloops. Furthermore, we investigate the protein binding pockets that accommodate single extruded nucleotides either involved in kink-turns or in arbitrary RNA strands. This analysis reveals a new structural motif, called tripod. It corresponds to small pockets consisting of three aminoacids arranged at the vertices of an almost equilateral triangle. We developed a search procedure for the recognition of tripods, based on an empirical tripod fingerprint. Conclusion A comparative analysis with the overall RNA surface and interfaces shows that contact surfaces involving RNA motifs have distinctive features that may be useful for the recognition and prediction of interactions. PMID:20122215

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

    PubMed Central

    2013-01-01

    Background Discovering transcription factor binding sites (TFBS) is one of primary challenges to decipher complex gene regulatory networks encrypted in a genome. A set of short DNA sequences identified by a transcription factor (TF) is known as a motif, which can be expressed accurately in matrix form such as a position-specific scoring matrix (PSSM) and a position frequency matrix. Very frequently, we need to query a motif in a database of motifs by seeking its similar motifs, merge similar TFBS motifs possibly identified by the same TF, separate irrelevant motifs, or filter out spurious motifs. Therefore, a novel metric is required to seize slight differences between irrelevant motifs and highlight the similarity between motifs of the same group in all these applications. While there are already several metrics for motif similarity proposed before, their performance is still far from satisfactory for these applications. Methods A novel metric has been proposed in this paper with name as SPIC (Similarity with Position Information Contents) for measuring the similarity between a column of a motif and a column of another motif. When defining this similarity score, we consider the likelihood that the column of the first motif's PFM can be produced by the column of the second motif's PSSM, and multiply the likelihood by the information content of the column of the second motif's PSSM, and vise versa. We evaluated the performance of SPIC combined with a local or a global alignment method having a function for affine gap penalty, for computing the similarity between two motifs. We also compared SPIC with seven existing state-of-the-arts metrics for their capability of clustering motifs from the same group and retrieving motifs from a database on three datasets. Results When used jointly with the Smith-Waterman local alignment method with an affine gap penalty function (gap open penalty is equal to1, gap extension penalty is equal to 0.5), SPIC outperforms the seven

  5. 73. PASSAGE ADJACENT TO ROOM 232, EAST WING, SECOND FLOOR, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    73. PASSAGE ADJACENT TO ROOM 232, EAST WING, SECOND FLOOR, LOOKING WEST BY NORTHWEST, SHOWING EASTERNMOST ARCH OF FORMER GREAT HALL NORTH ARCADE - Smithsonian Institution Building, 1000 Jefferson Drive, between Ninth & Twelfth Streets, Southwest, Washington, District of Columbia, DC

  6. View of viaduct, looking SE from roof of adjacent parking ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    View of viaduct, looking SE from roof of adjacent parking garage. - Mulberry Street Viaduct, Spanning Paxton Creek & Cameron Street (State Route 230) at Mulberry Street (State Route 3012), Harrisburg, Dauphin County, PA

  7. Cement Leakage into Adjacent Vertebral Body Following Percutaneous Vertebroplasty

    PubMed Central

    Park, Jae Hoo; Kim, Hyeun Sung

    2016-01-01

    Percutaneous vertebroplasty (PV) is a minimally invasive procedure for osteoporotic vertebral compression fractures that fail to respond to conventional conservative treatment. It significantly improves intolerable back pain within hours, and has a low complication rate. Although rare, PV is not free of complications, most of which are directly related to cement leakage. Because of its association with new adjacent fracture, the importance of cement leakage into the adjacent disc space is paramount. Here, we report an interesting case of cement leakage into the adjacent upper vertebral body as well as disc space following PV. To the best of our knowledge, there has been no report of cement leakage into the adjacent vertebral body following PV. This rare case is presented along with a review of the literature. PMID:27437018

  8. 1. HEBRONVILLE MILL COMPLEX ADJACENT TO NORTHEAST CORRIDOR. HEBRONVILLE, BRISTOL ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. HEBRONVILLE MILL COMPLEX ADJACENT TO NORTHEAST CORRIDOR. HEBRONVILLE, BRISTOL CO., MA. Sec. 4116, MP 193.75. - Northeast Railroad Corridor, Amtrak Route between RI/MA State Line & South Station, Boston, Suffolk County, MA

  9. 3. DODGEVILLE MILL COMPLEX ADJACENT TO NORTHEAST CORRIDOR DODGEVILLE, BRISTOL ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    3. DODGEVILLE MILL COMPLEX ADJACENT TO NORTHEAST CORRIDOR DODGEVILLE, BRISTOL CO., MA. Sec. 4116, MP 195.55. - Northeast Railroad Corridor, Amtrak Route between RI/MA State Line & South Station, Boston, Suffolk County, MA

  10. 33. HISTORIC PLAQUE MARKING WHERE JOHNSTON DIED, ADJACENT TO PATHWAY ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    33. HISTORIC PLAQUE MARKING WHERE JOHNSTON DIED, ADJACENT TO PATHWAY WITH CONCRETE CULVERT LEADING NORTH OUT OF RAVINE TOWARD JOHNSTON MEMORIAL SITE. VIEW NW. - Shiloh National Military Park Tour Roads, Shiloh, Hardin County, TN

  11. Lock 4 View east of lock wall and adjacent ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Lock 4 - View east of lock wall and adjacent roadway built atop tow path. The gate pocket can be seen at center. - Savannah & Ogeechee Barge Canal, Between Ogeechee & Savannah Rivers, Savannah, Chatham County, GA

  12. 1. Ninth Street (west) facade. Adjacent on the north is ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. Ninth Street (west) facade. Adjacent on the north is the 9th Street facade of 816 E Street. Both buildings were originally one property. - Riley Building, Rendezvous Adult Magazines & Films, 437 Ninth Street, Northwest, Washington, District of Columbia, DC

  13. 2. THREEQUARTER VIEW FROM ADJACENT ACCESS ROAD SHOWING THREE SPANS ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    2. THREE-QUARTER VIEW FROM ADJACENT ACCESS ROAD SHOWING THREE SPANS AND NORTHWEST APPROACH SPANS, LOOKING SOUTHEAST - Red River Bridge, Spanning Red River at U.S. Highway 82, Garland, Miller County, AR

  14. 1. VIEW FROM ROOFTOP OF BUILDING (MOTEL) ADJACENT TO TECHWOOD ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. VIEW FROM ROOFTOP OF BUILDING (MOTEL) ADJACENT TO TECHWOOD HOMES, LOOKING SOUTH. GARAGE TO EXTREME LEFT, BUILDING 1 TO EXTREME RIGHT. - Techwood Homes (Public Housing), Bounded by North Avenue, Parker Street, William Street & Lovejoy Street, Atlanta, Fulton County, GA

  15. 3. View of north side of house facing from adjacent ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    3. View of north side of house facing from adjacent vacant property. Original wood lap siding and trim is covered by aluminum siding. Recessed side porch is in middle. - 645 South Eighteenth Street (House), Louisville, Jefferson County, KY

  16. 1. A BRICK AND CONCRETE FAN HOUSING ADJACENT TO ONE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. A BRICK AND CONCRETE FAN HOUSING ADJACENT TO ONE OF THE ADIT OPENINGS (VIEW TO THE NORTH). - Foster Gulch Mine, Fan Housing, Bear Creek 1 mile Southwest of Town of Bear Creek, Red Lodge, Carbon County, MT

  17. 7. August, 1970 9 ORANGE STREET, ADJACENT TO UNITARIAN CHURCH ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    7. August, 1970 9 ORANGE STREET, ADJACENT TO UNITARIAN CHURCH (NOT IN STUDY AREA) - Orange & Union Streets Neighborhood Study, 8-31 Orange Street, 9-21 Union Street & Stone Alley, Nantucket, Nantucket County, MA

  18. OBLIQUE OF SOUTHWEST END AND SOUTHEAST SIDE, WITH ADJACENT FACILITY ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    OBLIQUE OF SOUTHWEST END AND SOUTHEAST SIDE, WITH ADJACENT FACILITY 391 IN THE FOREGROUND. - U.S. Naval Base, Pearl Harbor, Joint Intelligence Center, Makalapa Drive in Makalapa Administration Area, Pearl City, Honolulu County, HI

  19. Complications in exodontia--accidental dislodgment to adjacent anatomical areas.

    PubMed

    Grandini, S A; Barros, V M; Salata, L A; Rosa, A L; Soares, U N

    1993-01-01

    The authors report 4 cases of accidental dislodgement of teeth to adjacent anatomical areas during extraction. The causes and their prevention are discussed and solutions for the problem are suggested. PMID:8241759

  20. 6. Detail, vertical guides adjacent to east portal of Tunnel ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    6. Detail, vertical guides adjacent to east portal of Tunnel 28, view to southwest, 135mm lens with electronic flash fill. - Central Pacific Transcontinental Railroad, Tunnel No. 28, Milepost 134.75, Applegate, Placer County, CA

  1. VIEW OF CONSTRUCTION CAMP ROCK FEATURE WITH OVER, ADJACENT TO ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    VIEW OF CONSTRUCTION CAMP ROCK FEATURE WITH OVER, ADJACENT TO THE COLUMBIA SOUTHERN CANAL. LOOKING NORTHWEST - Tumalo Irrigation District, Tumalo Project, West of Deschutes River, Tumalo, Deschutes County, OR

  2. Pump house adjacent to the superintendent's house at the west ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Pump house adjacent to the superintendent's house at the west end of the complex near Highway 101. Detail of Holloshaft pump. View to the south. - Prairie Creek Fish Hatchery, Hwy. 101, Orick, Humboldt County, CA

  3. VIEW OF NORTHERN AND EASTERN SIDES FROM PARKING LOT ADJACENT ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    VIEW OF NORTHERN AND EASTERN SIDES FROM PARKING LOT ADJACENT TO BUILDING 199 (POLICE STATION) - U.S. Naval Base, Pearl Harbor, Post Office, Avenue A near Eleventh Avenue, Pearl City, Honolulu County, HI

  4. 24. INTERIOR VIEW, WILLIAM GRAY AT SIZING GUAGE ADJACENT TO ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    24. INTERIOR VIEW, WILLIAM GRAY AT SIZING GUAGE ADJACENT TO BRADLEY HAMMER; NOTE THIS IS THE SAME TOOL AS BEING FORGED ABOVE - Warwood Tool Company, Foot of Nineteenth Street, Wheeling, Ohio County, WV

  5. Detail exterior view looking north showing piping system adjacent to ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Detail exterior view looking north showing piping system adjacent to engine house. Gas cooling system is on far right. - Burnsville Natural Gas Pumping Station, Saratoga Avenue between Little Kanawha River & C&O Railroad line, Burnsville, Braxton County, WV

  6. VIEW OF LAMP FIXTURE (EXTERIOR) ADJACENT TO ENTRANCE AT SOUTHWEST ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    VIEW OF LAMP FIXTURE (EXTERIOR) ADJACENT TO ENTRANCE AT SOUTHWEST CORNER OF BUILDING 23, FACING NORTH - Roosevelt Base, Auditorium-Gymnasium, West Virginia Street between Richardson & Reeves Avenues, Long Beach, Los Angeles County, CA

  7. 14. Charles Acey Cobb standing adjacent to the fish screen ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    14. Charles Acey Cobb standing adjacent to the fish screen he designed and installed in the Congdon Canal, facing southeast. Photo dates ca. late 1920's. - Congdon Canal, Fish Screen, Naches River, Yakima, Yakima County, WA

  8. 52. EASTSIDE PLANT: GENERAL VIEW OF GOVERNOR ADJACENT TO GENERATOR ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    52. EASTSIDE PLANT: GENERAL VIEW OF GOVERNOR ADJACENT TO GENERATOR - American Falls Water, Power & Light Company, Island Power Plant, Snake River, below American Falls Dam, American Falls, Power County, ID

  9. Interior building details of Building A, dungeon cell adjacent to ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Interior building details of Building A, dungeon cell adjacent to northwest cell: granite and brick threshold, poured concrete floors, plastered finished walls, vaulted veiling; northwesterly view - San Quentin State Prison, Building 22, Point San Quentin, San Quentin, Marin County, CA

  10. VIEW OF CONCRETE CHANNEL ADJACENT TO TUMALO FEED CANAL INTAKE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    VIEW OF CONCRETE CHANNEL ADJACENT TO TUMALO FEED CANAL INTAKE STRUCTURE (DOWNSTREAM SIDE). LOOKING EAST/NORTHEAST - Tumalo Irrigation District, Tumalo Project, West of Deschutes River, Tumalo, Deschutes County, OR

  11. Using the Gibbs Motif Sampler for Phylogenetic Footprinting

    SciTech Connect

    Thompson, William; Conlan, Sean; McCue, Lee Ann; Lawrence, Charles

    2007-07-01

    The Gibbs Motif Sampler (Gibbs) (1) is a software package used to predict conserved elements in biopolymer sequences. While the software can be used to locate conserved motifs in protein sequences, its most common use is the prediction of transcription factor binding sites (TFBSs) in promoters upstream of gene sequences. We will describe approaches that use Gibbs to locate TFBSs in a collection of orthologous nucleotide sequences, i.e. phylogenetic footprinting. To illustrate this technique, we present examples that use Gibbs to detect binding sites for the transcription factor LexA in orthologous sequence data from representative species belonging to two different proteobacterial divisions.

  12. Adjacent Segment Disease Perspective and Review of the Literature

    PubMed Central

    Saavedra-Pozo, Fanor M.; Deusdara, Renato A. M.; Benzel, Edward C.

    2014-01-01

    Background Adjacent segment disease has become a common topic in spine surgery circles because of the significant increase in fusion surgery in recent years and the development of motion preservation technologies that theoretically should lead to a decrease in this pathology. The purpose of this review is to organize the evidence available in the current literature on this subject. Methods For this literature review, a search was conducted in PubMed with the following keywords: adjacent segment degeneration and disease. Selection, review, and analysis of the literature were completed according to level of evidence. Results The PubMed search identified 850 articles, from which 41 articles were selected and reviewed. The incidence of adjacent segment disease in the cervical spine is close to 3% without a significant statistical difference between surgical techniques (fusion vs arthroplasty). Authors report the incidence of adjacent segment disease in the lumbar spine to range from 2% to 14%. Damage to the posterior ligamentous complex and sagittal imbalances are important risk factors for both degeneration and disease. Conclusion Insufficient evidence exists at this point to support the idea that total disc arthroplasty is superior to fusion procedures in minimizing the incidence of adjacent segment disease. The etiology is most likely multifactorial but it is becoming abundantly clear that adjacent segment disease is not caused by motion segment fusion alone. Fusion plus the presence of abnormal end-fusion alignment appears to be a major factor in creating end-fusion stresses that result in adjacent segment degeneration and subsequent disease. The data presented cast further doubt on previously established rationales for total disc arthroplasty, at least with regard to the effect of total disc arthroplasty on adjacent segment degeneration pathology. PMID:24688337

  13. Approximating the largest eigenvalue of network adjacency matrices

    NASA Astrophysics Data System (ADS)

    Restrepo, Juan G.; Ott, Edward; Hunt, Brian R.

    2007-11-01

    The largest eigenvalue of the adjacency matrix of a network plays an important role in several network processes (e.g., synchronization of oscillators, percolation on directed networks, and linear stability of equilibria of network coupled systems). In this paper we develop approximations to the largest eigenvalue of adjacency matrices and discuss the relationships between these approximations. Numerical experiments on simulated networks are used to test our results.

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

    PubMed

    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. PMID:23646825

  15. 52 Gbps PAM4 receiver sensitivity study for 400GBase-LR8 system using directly modulated laser.

    PubMed

    Motaghiannezam, Reza; Pham, Thang; Chen, Alan; Du, Tengda; Kocot, Chris; Xu, Jack; Huebner, Bernd

    2016-04-01

    Real-time 52 Gbps PAM4 transmission is demonstrated over single mode fiber (SMF) using a directly modulated laser (DML) and a PHY chip. The inner eye optical modulation amplitude (OMA) receiver sensitivities were measured and compared using avalanche photodetector (APD) and PIN photodetector (PD) for the maximum and minimum chromatic dispersions (CDs) of 400GBase-LR8 link. The measured inner eye OMAs were -17.8 dBm and -18.8 dBm for + 10 ps/nm and -58 ps/nm of CDs at the KP4 bit error rate (BER) threshold of 2 × 10-4 using a PIN PD, respectively. The measured inner eye OMA was improved to -21.0 dBm for -58 ps/nm of CD at the KP4 BER threshold using an APD. Negligible OMA penalty (< 0.4 dB) was captured for operating DML at different bias currents of 40 mA and 60 mA using a PIN PD and an APD for both positive and negative CDs at the KP4 BER threshold. PMID:27137027

  16. New York State Department of Environmental Conservation PAMS monitoring system using a 3-column, double identification GC

    SciTech Connect

    Sierzenga, P.M.; Boynton, G.A.; Aho, B.J.

    1996-12-31

    New York State conducted its 1995 PAMS measurements for New York City in the Bronx borough (New York Botanical Gardens) using a Perkin-Elmer ATD-400 Thermal Desorbtion Unit with an 8000 Series Gas Chromatograph. Data was collected in New York City, transferred to Albany, and processed in the central office. The system was checked on a daily basis from Albany to verify operation. Quality assurance for the system was provided by collecting a one hour collocated canister sample every day with analysis performed in Albany using a GC-MS system. The normal configuration for the Perkin-Elmer system uses only two columns, a PLOT column to separate low weight hydrocarbons (C{sub 2}-C{sub 5}) and a BP-1 column to separate higher weight hydrocarbons (C{sub 6}-C{sub 10}). New York`s custom designed system uses a third RTX-5 column to provide a second identification and quantitation of most target hydrocarbons. Analysis of the 1995 data provides insight into the usefulness of the third column in correcting both misidentified peaks and over-quantification of compound concentrations found using the standard configuration alone. The 1995 data set also allows an examination of the increased complexity versus the benefits of the system modification. 6 figs., 1 tab.

  17. Arsenic toxicity in the water weed Wolffia arrhiza measured using Pulse Amplitude Modulation Fluorometry (PAM) measurements of photosynthesis.

    PubMed

    Ritchie, Raymond J; Mekjinda, Nutsara

    2016-10-01

    Accumulation of arsenic in plants is a serious South-east Asian environmental problem. Photosynthesis in the small aquatic angiosperm Wolffia arrhiza is very sensitive to arsenic toxicity, particularly in water below pH 7 where arsenite (As (OH)3) (AsIII) is the dominant form; at pH >7 AsO4(2-) (As(V) predominates). A blue-diode PAM (Pulse Amplitude Fluorometer) machine was used to monitor photosynthesis in Wolffia. Maximum gross photosynthesis (Pgmax) and not maximum yield (Ymax) is the most reliable indicator of arsenic toxicity. The toxicity of arsenite As(III) and arsenate (H2AsO4(2-)) As(V) vary with pH. As(V) was less toxic than As(III) at both pH 5 and pH 8 but both forms of arsenic were toxic (>90% inhibition) at below 0.1molm(-3) when incubated in arsenic for 24h. Arsenite toxicity was apparent after 1h based on Pgmax and gradually increased over 7h but there was no apparent effect on Ymax or photosynthetic efficiency (α0). PMID:27318559

  18. Adh enhances Actinobacillus pleuropneumoniae pathogenicity by binding to OR5M11 and activating p38 which induces apoptosis of PAMs and IL-8 release

    PubMed Central

    Wang, Lei; Qin, Wanhai; Zhang, Jing; Bao, Chuntong; Zhang, Hu; Che, Yanyi; Sun, Changjiang; Gu, Jingmin; Feng, Xin; Du, Chongtao; Han, Wenyu; Richard, Paul Langford; Lei, Liancheng

    2016-01-01

    Members of the Trimeric Autotransporter Adhesin (TAA) family play a crucial role in the adhesion of Gram-negative pathogens to host cells, but the immunopathogenesis of TAAs remains unknown. Our previous studies demonstrated that Adh from Actinobacillus pleuropneumoniae (A. pleuropneumoniae) is required for full bacterial pathogenicity. Alveolar macrophages are the first line of defense against respiratory infections. This study compared the interactions between porcine alveolar macrophages (PAMs) and wild-type A. pleuropneumoniae (5b WT) or an Adh-deletion strain (5b ΔAdh) via gene microarray, immunoprecipitation and other technologies. We found that Adh was shown to interact with the PAMs membrane protein OR5M11, an olfactory receptor, resulting in the high-level secretion of IL-8 by activation of p38 MAPK signaling pathway. Subsequently, PAMs apoptosis via the activation of the Fax and Bax signaling pathways was observed, followed by activation of caspases 8, 9, and 3. The immunological pathogenic roles of Adh were also confirmed in both murine and piglets infectious models in vivo. These results identify a novel immunological strategy for TAAs to boost the pathogenicity of A. pleuropneumoniae. Together, these datas reveal the high versatility of the Adh protein as a virulence factor and provide novel insight into the immunological pathogenic role of TAAs. PMID:27046446

  19. Regulation of GM-CSF and IL-3 production from the murine keratinocyte cell line PAM 212 following exposure to ultraviolet radiation

    SciTech Connect

    Gallo, R.L.; Staszewski, R.; Sauder, D.N.; Knisely, T.L.; Granstein, R.D. )

    1991-08-01

    Ultraviolet radiation (UVR) exposure induces profound changes in the synthesis and secretion of various cytokines both in vivo and in vitro. Little is known regarding the mechanism of these responses. This investigation evaluated the effects of UVR on the ability of a murine keratinocyte line (PAM 212) to produce interleukin 3 (IL-3) and granulocyte-macrophage colony stimulating factor (GM-CSF). Subconfluent rapidly dividing PAM 212 cells were shown by RNA slot-blot hybridization studies to have increased levels of mRNA for both IL-3 and GM-CSF within 1 h of UVR exposure. However, only GM-CSF-specific bioactivity, as determined by antibody neutralization studies, was shown to increase above baseline in cell supernatants. Cells grown to confluence responded differently to UVR. Under these culture conditions an apparent decrease in bioactivity was detected after UVR exposure for both growth factors, and no change in mRNA levels was detected. In addition to culture density, removal of extracellular calcium or sodium during irradiation, treatment with amiloride, or inhibition of new mRNA synthesis with cordycepin was shown to influence the UVR-induced alteration in release of IL-3 or GM-CSF bioactivity from both confluent and subconfluent PAM 212 cells. These results demonstrate that UVR influences the release of the colony stimulating factors GM-CSF and IL-3 from keratinocyte, and suggests that the state of cell growth and conditions of membrane ion transport influence the mechanisms regulating secretion of those factors.

  20. Effect of the synthetic Toll-like receptor ligands LPS, Pam3CSK4, HKLM and FSL-1 in the function of bovine polymorphonuclear neutrophils.

    PubMed

    Conejeros, Iván; Gibson, Amanda J; Werling, Dirk; Muñoz-Caro, Tamara; Hermosilla, Carlos; Taubert, Anja; Burgos, Rafael A

    2015-10-01

    Toll-like receptors (TLR) are a family of pattern recognition receptors that sense microbial associated molecular patterns (MAMP) such as microbial membrane components and nucleic acids of bacterial origin. Polymorphonuclear neutrophils (PMN) are the first cell of the innate immune system to arrive at the site of infection or injury and elicit oxidative and non-oxidative microbicidal mechanisms. Observations in human and mouse suggest that TLR ligands can induce direct responses in PMN. So far, there is no information of the effect of synthetic TLR ligands on the response of bovine PMN. The objective of this study was to evaluate the functional response of bovine PMN incubated with four synthetic TLR ligands: ultrapure LPS (TLR4), Pam(3)CSK(4) (TLR2/1), HKLM (TLR2) and FSL-1 (TLR2/6). The results show that all the ligands increment cells size as identified by changes in the FSC-SSC as part of the flow cytometric analysis. Interestingly, only Pam(3)CSK(4) consistently induced a calcium influx, increased ROS production and secretion of gelatinase granules, whereas no response was seen using other ligands. Furthermore, exposure of bovine PMN to ultrapure LPS, Pam(3)CSK(4), HKLM or FSL-1 for 24 hours did not impact on apoptosis of these cells. Our data provide evidence for a selective response of bovine PMNs to TLR ligands. PMID:26026246

  1. Redemptive Journey: The Storytelling Motif in Andersen's "The Snow Queen."

    ERIC Educational Resources Information Center

    Misheff, Sue

    1989-01-01

    Discusses how Hans Christian Andersen's "The Snow Queen" uses the motif of storytelling to describe the journey taken by the heroine Gerda. Identifies a story as that which is alive and active and which causes catharsis for those who participate in it. (MG)

  2. Fast, Sensitive Discovery of Conserved Genome-Wide Motifs

    PubMed Central

    Ihuegbu, Nnamdi E.; Buhler, Jeremy

    2012-01-01

    Abstract Regulatory sites that control gene expression are essential to the proper functioning of cells, and identifying them is critical for modeling regulatory networks. We have developed Magma (Multiple Aligner of Genomic Multiple Alignments), a software tool for multiple species, multiple gene motif discovery. Magma identifies putative regulatory sites that are conserved across multiple species and occur near multiple genes throughout a reference genome. Magma takes as input multiple alignments that can include gaps. It uses efficient clustering methods that make it about 70 times faster than PhyloNet, a previous program for this task, with slightly greater sensitivity. We ran Magma on all non-coding DNA conserved between Caenorhabditis elegans and five additional species, about 70 Mbp in total, in <4 h. We obtained 2,309 motifs with lengths of 6–20 bp, each occurring at least 10 times throughout the genome, which collectively covered about 566 kbp of the genomes, approximately 0.8% of the input. Predicted sites occurred in all types of non-coding sequence but were especially enriched in the promoter regions. Comparisons to several experimental datasets show that Magma motifs correspond to a variety of known regulatory motifs. PMID:22300316

  3. Motifs in triadic random graphs based on Steiner triple systems

    NASA Astrophysics Data System (ADS)

    Winkler, Marco; Reichardt, Jörg

    2013-08-01

    Conventionally, pairwise relationships between nodes are considered to be the fundamental building blocks of complex networks. However, over the last decade, the overabundance of certain subnetwork patterns, i.e., the so-called motifs, has attracted much attention. It has been hypothesized that these motifs, instead of links, serve as the building blocks of network structures. Although the relation between a network's topology and the general properties of the system, such as its function, its robustness against perturbations, or its efficiency in spreading information, is the central theme of network science, there is still a lack of sound generative models needed for testing the functional role of subgraph motifs. Our work aims to overcome this limitation. We employ the framework of exponential random graph models (ERGMs) to define models based on triadic substructures. The fact that only a small portion of triads can actually be set independently poses a challenge for the formulation of such models. To overcome this obstacle, we use Steiner triple systems (STSs). These are partitions of sets of nodes into pair-disjoint triads, which thus can be specified independently. Combining the concepts of ERGMs and STSs, we suggest generative models capable of generating ensembles of networks with nontrivial triadic Z-score profiles. Further, we discover inevitable correlations between the abundance of triad patterns, which occur solely for statistical reasons and need to be taken into account when discussing the functional implications of motif statistics. Moreover, we calculate the degree distributions of our triadic random graphs analytically.

  4. DNA containing CpG motifs induces angiogenesis

    NASA Astrophysics Data System (ADS)

    Zheng, Mei; Klinman, Dennis M.; Gierynska, Malgorzata; Rouse, Barry T.

    2002-06-01

    New blood vessel formation in the cornea is an essential step in the pathogenesis of a blinding immunoinflammatory reaction caused by ocular infection with herpes simplex virus (HSV). By using a murine corneal micropocket assay, we found that HSV DNA (which contains a significant excess of potentially bioactive "CpG" motifs when compared with mammalian DNA) induces angiogenesis. Moreover, synthetic oligodeoxynucleotides containing CpG motifs attract inflammatory cells and stimulate the release of vascular endothelial growth factor (VEGF), which in turn triggers new blood vessel formation. In vitro, CpG DNA induces the J774A.1 murine macrophage cell line to produce VEGF. In vivo CpG-induced angiogenesis was blocked by the administration of anti-mVEGF Ab or the inclusion of "neutralizing" oligodeoxynucleotides that specifically oppose the stimulatory activity of CpG DNA. These findings establish that DNA containing bioactive CpG motifs induces angiogenesis, and suggest that CpG motifs in HSV DNA may contribute to the blinding lesions of stromal keratitis.

  5. 5. DETAIL VIEW OF THE EGYPTIAN MOTIF DECORATIVE ELEMENTS OF ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. DETAIL VIEW OF THE EGYPTIAN MOTIF DECORATIVE ELEMENTS OF BUILDING 1'S MAIN ENTRY TOWER (INCLUDING THE ENGAGED COLUMN CAPITALS, PILASTERS & CAPITALS, CORNICES, AND TERRA COTTA EAGLES); LOOKING SW FROM THE E WING ROOF. (Ryan) - Veterans Administration Medical Center, Building No. 1, Old State Route 13 West, Marion, Williamson County, IL

  6. Variable structure motifs for transcription factor binding sites

    PubMed Central

    2010-01-01

    Background Classically, models of DNA-transcription factor binding sites (TFBSs) have been based on relatively few known instances and have treated them as sites of fixed length using position weight matrices (PWMs). Various extensions to this model have been proposed, most of which take account of dependencies between the bases in the binding sites. However, some transcription factors are known to exhibit some flexibility and bind to DNA in more than one possible physical configuration. In some cases this variation is known to affect the function of binding sites. With the increasing volume of ChIP-seq data available it is now possible to investigate models that incorporate this flexibility. Previous work on variable length models has been constrained by: a focus on specific zinc finger proteins in yeast using restrictive models; a reliance on hand-crafted models for just one transcription factor at a time; and a lack of evaluation on realistically sized data sets. Results We re-analysed binding sites from the TRANSFAC database and found motivating examples where our new variable length model provides a better fit. We analysed several ChIP-seq data sets with a novel motif search algorithm and compared the results to one of the best standard PWM finders and a recently developed alternative method for finding motifs of variable structure. All the methods performed comparably in held-out cross validation tests. Known motifs of variable structure were recovered for p53, Stat5a and Stat5b. In addition our method recovered a novel generalised version of an existing PWM for Sp1 that allows for variable length binding. This motif improved classification performance. Conclusions We have presented a new gapped PWM model for variable length DNA binding sites that is not too restrictive nor over-parameterised. Our comparison with existing tools shows that on average it does not have better predictive accuracy than existing methods. However, it does provide more interpretable

  7. Discovering common stem–loop motifs in unaligned RNA sequences

    PubMed Central

    Gorodkin, Jan; Stricklin, Shawn L.; Stormo, Gary D.

    2001-01-01

    Post-transcriptional regulation of gene expression is often accomplished by proteins binding to specific sequence motifs in mRNA molecules, to affect their translation or stability. The motifs are often composed of a combination of sequence and structural constraints such that the overall structure is preserved even though much of the primary sequence is variable. While several methods exist to discover transcriptional regulatory sites in the DNA sequences of coregulated genes, the RNA motif discovery problem is much more difficult because of covariation in the positions. We describe the combined use of two approaches for RNA structure prediction, FOLDALIGN and COVE, that together can discover and model stem–loop RNA motifs in unaligned sequences, such as UTRs from post-transcriptionally coregulated genes. We evaluate the method on two datasets, one a section of rRNA genes with randomly truncated ends so that a global alignment is not possible, and the other a hyper-variable collection of IRE-like elements that were inserted into randomized UTR sequences. In both cases the combined method identified the motifs correctly, and in the rRNA example we show that it is capable of determining the structure, which includes bulge and internal loops as well as a variable length hairpin loop. Those automated results are quantitatively evaluated and found to agree closely with structures contained in curated databases, with correlation coefficients up to 0.9. A basic server, Stem–Loop Align SearcH (SLASH), which will perform stem–loop searches in unaligned RNA sequences, is available at http://www.bioinf.au.dk/slash/. PMID:11353083

  8. The RNA polymerase bridge helix YFI motif in catalysis, fidelity and translocation

    PubMed Central

    Nedialkov, Yuri A.; Opron, Kristopher; Assaf, Fadi; Artsimovitch, Irina; Kireeva, Maria L.; Kashlev, Mikhail; Cukier, Robert I.; Nudler, Evgeny; Burton, Zachary F.

    2013-01-01

    The bridge α-helix in the β′ subunit of RNA polymerase (RNAP) borders the active site and may have roles in catalysis and translocation. In Escherichia coli RNAP, a bulky hydrophobic segment near the N-terminal end of the bridge helix is identified (β′ 772-YFI-774; the YFI motif). YFI is located at a distance from the active center and adjacent to a glycine hinge (β′ 778-GARKG-782) involved in dynamic bending of the bridge helix. Remarkably, amino acid substitutions in YFI significantly alter intrinsic termination, pausing, fidelity and translocation of RNAP. F773V RNAP largely ignores the λ tR2 terminator at 200 µM NTPs and is strongly reduced in λ tR2 recognition at 1 µM NTPs. F773V alters RNAP pausing and backtracking and favors misincorporation. By contrast, the adjacent Y772A substitution increases fidelity and exhibits other transcriptional defects generally opposite to those of F773V. All atom molecular dynamics simulation revealed two separate functional connections emanating from YFI explaining the distinct effects of substitutions: Y772 communicates with the active site through the link domain in the β subunit, whereas F773 communicates through the fork domain in the β subunit. I774 interacts with the F-loop, which also contacts the glycine hinge of the bridge helix. These results identified negative and positive circuits coupled at YFI and employed for regulation of catalysis, elongation, termination and translocation. PMID:23202476

  9. Composite motifs integrating multiple protein structures increase sensitivity for function prediction.

    PubMed

    Chen, Brian Y; Bryant, Drew H; Cruess, Amanda E; Bylund, Joseph H; Fofanov, Viacheslav Y; Kristensen, David M; Kimmel, Marek; Lichtarge, Olivier; Kavraki, Lydia E

    2007-01-01

    The study of disease often hinges on the biological function of proteins, but determining protein function is a difficult experimental process. To minimize duplicated effort, algorithms for function prediction seek characteristics indicative of possible protein function. One approach is to identify substructural matches of geometric and chemical similarity between motifs representing known active sites and target protein structures with unknown function. In earlier work, statistically significant matches of certain effective motifs have identified functionally related active sites. Effective motifs must be carefully designed to maintain similarity to functionally related sites (sensitivity) and avoid incidental similarities to functionally unrelated protein geometry (specificity). Existing motif design techniques use the geometry of a single protein structure. Poor selection of this structure can limit motif effectiveness if the selected functional site lacks similarity to functionally related sites. To address this problem, this paper presents composite motifs, which combine structures of functionally related active sites to potentially increase sensitivity. Our experimentation compares the effectiveness of composite motifs with simple motifs designed from single protein structures. On six distinct families of functionally related proteins, leave-one-out testing showed that composite motifs had sensitivity comparable to the most sensitive of all simple motifs and specificity comparable to the average simple motif. On our data set, we observed that composite motifs simultaneously capture variations in active site conformation, diminish the problem of selecting motif structures, and enable the fusion of protein structures from diverse data sources. PMID:17951837

  10. Laplacian versus adjacency matrix in quantum walk search

    NASA Astrophysics Data System (ADS)

    Wong, Thomas G.; Tarrataca, Luís; Nahimov, Nikolay

    2016-06-01

    A quantum particle evolving by Schrödinger's equation contains, from the kinetic energy of the particle, a term in its Hamiltonian proportional to Laplace's operator. In discrete space, this is replaced by the discrete or graph Laplacian, which gives rise to a continuous-time quantum walk. Besides this natural definition, some quantum walk algorithms instead use the adjacency matrix to effect the walk. While this is equivalent to the Laplacian for regular graphs, it is different for non-regular graphs and is thus an inequivalent quantum walk. We algorithmically explore this distinction by analyzing search on the complete bipartite graph with multiple marked vertices, using both the Laplacian and adjacency matrix. The two walks differ qualitatively and quantitatively in their required jumping rate, runtime, sampling of marked vertices, and in what constitutes a natural initial state. Thus the choice of the Laplacian or adjacency matrix to effect the walk has important algorithmic consequences.

  11. The impact of RNA binding motif protein 4-regulated splicing cascade on the progression and metabolism of colorectal cancer cells

    PubMed Central

    Lin, Ying-Ju; Lin, Jung-Chun

    2015-01-01

    Dysregulated splicing of pre-messenger (m)RNA is considered a molecular occasion of carcinogenesis. However, the underlying mechanism is complex and remains to be investigated. Herein, we report that the upregulated miR-92a reduced the RNA-binding motif 4 (RBM4) protein expression, leading to the imbalanced expression of the neuronal polypyrimidine tract-binding (nPTB) protein through alternative splicing-coupled nonsense mediated decay (NMD) mechanism. Increase in nPTB protein enhances the relative level of fibroblast growth factor receptor 2 IIIc (FGFR2) and pyruvate kinase M2 (PKM2) transcripts which contribute to the progression and metabolic signature of CRC cells. Expression profiles of RBM4 and downstream alternative splicing events are consistently observed in cancerous tissues compared to adjacent normal tissues. These results constitute a mechanistic understanding of RBM4 on repressing the carcinogenesis of colorectal cells. PMID:26506517

  12. The i-Motif in the bcl-2 P1 Promoter Forms an Unexpectedly Stable Structure with a Unique 8:5:7 Loop Folding Pattern

    PubMed Central

    Kendrick, Samantha; Akiyama, Yoshitsugu; Hecht, Sidney M.; Hurley, Laurence H.

    2009-01-01

    Transcriptional regulation of the bcl-2 proto-oncogene is highly complex, with the majority of transcription driven by the P1 promoter site and the interaction of multiple regulatory proteins. A guanine- and cytosine-rich (GC-rich) region directly upstream of the P1 site has been shown to be integral to bcl-2 promoter activity, as deletion or mutation of this region significantly increases transcription. This GC-rich element consists of six contiguous runs of guanines and cytosines that have the potential to adopt DNA secondary structures, the G-quadruplex and i-motif, respectively. Our laboratory has previously demonstrated that the polypurine-rich strand of the bcl-2 promoter can form a mixture of three different G-quadruplex structures. In this current study, we demonstrate that the complementary polypyrimidine-rich strand is capable of forming one major intramolecular i-motif DNA secondary structure with a transition pH of 6.6. Characterization of the i-motif folding pattern using mutational studies coupled with circular dichroic spectra and thermal stability analyses revealed an 8:5:7 loop conformation as the predominant structure at pH 6.1. The folding pattern was further supported by chemical footprinting with bromine. In addition, a novel assay involving the sequential incorporation of a fluorescent thymine analog at each thymine position provided evidence of a capping structure within the top loop region of the i-motif. The potential of the GC-rich element within the bcl-2 promoter region to form DNA secondary structures suggests that the transition from the B-DNA to non-B-DNA conformation may play an important role in bcl-2 transcriptional regulation. Furthermore, the two adjacent large lateral loops in the i-motif structure provide an unexpected opportunity for protein and small molecule recognition. PMID:19908860

  13. Unusual conformation of the SxN motif in the crystal structure of penicillin-binding protein A from Mycobacterium tuberculosis.

    SciTech Connect

    Fedarovich, Alena; Nicholas, Robert A.; Davies, Christopher

    2010-07-19

    PBPA from Mycobacterium tuberculosis is a class B-like penicillin-binding protein (PBP) that is not essential for cell growth in M. tuberculosis, but is important for proper cell division in Mycobacterium smegmatis. We have determined the crystal structure of PBPA at 2.05 {angstrom} resolution, the first published structure of a PBP from this important pathogen. Compared to other PBPs, PBPA has a relatively small N-terminal domain, and conservation of a cluster of charged residues within this domain suggests that PBPA is more related to class B PBPs than previously inferred from sequence analysis. The C-terminal domain is a typical transpeptidase fold and contains the three conserved active-site motifs characterisitic of penicillin-interacting enzymes. While the arrangement of the SxxK and KTG motifs is similar to that observed in other PBPs, the SxN motif is markedly displaced away from the active site, such that its serine (Ser281) is not involved in hydrogen bonding with residues of the other two motifs. A disulfide bridge between Cys282 (the 'x' of the SxN motif) and Cys266, which resides on an adjacent loop, may be responsible for this unusual conformation. Another interesting feature of the structure is a relatively long connection between {beta}5 and {alpha}11, which restricts the space available in the active site of PBPA and suggests that conformational changes would be required to accommodate peptide substrate or {beta}-lactam antibiotics during acylation. Finally, the structure shows that one of the two threonines postulated to be targets for phosphorylation is inaccessible (Thr362), whereas the other (Thr437) is well placed on a surface loop near the active site.

  14. FPGA implementation of motifs-based neuronal network and synchronization analysis

    NASA Astrophysics Data System (ADS)

    Deng, Bin; Zhu, Zechen; Yang, Shuangming; Wei, Xile; Wang, Jiang; Yu, Haitao

    2016-06-01

    Motifs in complex networks play a crucial role in determining the brain functions. In this paper, 13 kinds of motifs are implemented with Field Programmable Gate Array (FPGA) to investigate the relationships between the networks properties and motifs properties. We use discretization method and pipelined architecture to construct various motifs with Hindmarsh-Rose (HR) neuron as the node model. We also build a small-world network based on these motifs and conduct the synchronization analysis of motifs as well as the constructed network. We find that the synchronization properties of motif determine that of motif-based small-world network, which demonstrates effectiveness of our proposed hardware simulation platform. By imitation of some vital nuclei in the brain to generate normal discharges, our proposed FPGA-based artificial neuronal networks have the potential to replace the injured nuclei to complete the brain function in the treatment of Parkinson's disease and epilepsy.

  15. On the Adjacent Eccentric Distance Sum Index of Graphs

    PubMed Central

    Qu, Hui; Cao, Shujuan

    2015-01-01

    For a given graph G, ε(v) and deg(v) denote the eccentricity and the degree of the vertex v in G, respectively. The adjacent eccentric distance sum index of a graph G is defined as ξsv(G)=∑v∈V(G)ε(v)D(v)deg(v), where D(v)=∑u∈V(G)d(u,v) is the sum of all distances from the vertex v. In this paper we derive some bounds for the adjacent eccentric distance sum index in terms of some graph parameters, such as independence number, covering number, vertex connectivity, chromatic number, diameter and some other graph topological indices. PMID:26091095

  16. Nonlinear spin wave coupling in adjacent magnonic crystals

    NASA Astrophysics Data System (ADS)

    Sadovnikov, A. V.; Beginin, E. N.; Morozova, M. A.; Sharaevskii, Yu. P.; Grishin, S. V.; Sheshukova, S. E.; Nikitov, S. A.

    2016-07-01

    We have experimentally studied the coupling of spin waves in the adjacent magnonic crystals. Space- and time-resolved Brillouin light-scattering spectroscopy is used to demonstrate the frequency and intensity dependent spin-wave energy exchange between the side-coupled magnonic crystals. The experiments and the numerical simulation of spin wave propagation in the coupled periodic structures show that the nonlinear phase shift of spin wave in the adjacent magnonic crystals leads to the nonlinear switching regime at the frequencies near the forbidden magnonic gap. The proposed side-coupled magnonic crystals represent a significant advance towards the all-magnonic signal processing in the integrated magnonic circuits.

  17. Molecular disorganization of axons adjacent to human lacunar infarcts

    PubMed Central

    Lee, Monica D.; Tung, Spencer; Vinters, Harry V.; Carmichael, S. Thomas

    2015-01-01

    Cerebral microvascular disease predominantly affects brain white matter and deep grey matter, resulting in ischaemic damage that ranges from lacunar infarcts to white matter hyperintensities seen on magnetic resonance imaging. These lesions are common and result in both clinical stroke syndromes and accumulate over time, resulting in cognitive deficits and dementia. Magnetic resonance imaging studies suggest that these lesions progress over time, accumulate adjacent to prior lesions and have a penumbral region susceptible to further injury. The pathological correlates of this adjacent injury in surviving myelinated axons have not been previously defined. In this study, we sought to determine the molecular organization of axons in tissue adjacent to lacunar infarcts and in the regions surrounding microinfarcts, by determining critical elements in axonal function: the morphology and length of node of Ranvier segments and adjacent paranodal segments. We examined post-mortem brain tissue from six patients with lacunar infarcts and tissue from two patients with autosomal dominant retinal vasculopathy and cerebral leukoencephalopathy (previously known as hereditary endotheliopathy with retinopathy, nephropathy and stroke) who accumulate progressive white matter ischaemic lesions in the form of lacunar and microinfarcts. In axons adjacent to lacunar infarcts yet extending up to 150% of the infarct diameter away, both nodal and paranodal length increase by ∼20% and 80%, respectively, reflecting a loss of normal cell-cell adhesion and signalling between axons and oligodendrocytes. Using premorbid magnetic resonance images, brain regions from patients with retinal vasculopathy and cerebral leukoencephalopathy that harboured periventricular white matter hyperintensities were selected and the molecular organization of axons was determined within these regions. As in regions adjacent to lacunar infarcts, nodal and paranodal length in white matter of these patients is

  18. Crystal Structure of a Luteoviral RNA Pseudoknot and Model for a Minimal Ribosomal Frameshifting Motif

    SciTech Connect

    Pallan, Pradeep S.; Marshall, William S.; Harp, Joel; Jewett III, Frederic C.; Wawrzak, Zdzislaw; Brown II, Bernard A.; Rich, Alexander; Egli, Martin

    2010-03-08

    To understand the role of structural elements of RNA pseudoknots in controlling the extent of -1-type ribosomal frameshifting, we determined the crystal structure of a high-efficiency frameshifting mutant of the pseudoknot from potato leaf roll virus (PLRV). Correlations of the structure with available in vitro frameshifting data for PLRV pseudoknot mutants implicate sequence and length of a stem-loop linker as modulators of frameshifting efficiency. Although the sequences and overall structures of the RNA pseudoknots from PLRV and beet western yellow virus (BWYV) are similar, nucleotide deletions in the linker and adjacent minor groove loop abolish frameshifting only with the latter. Conversely, mutant PLRV pseudoknots with up to four nucleotides deleted in this region exhibit nearly wild-type frameshifting efficiencies. The crystal structure helps rationalize the different tolerances for deletions in the PLRV and BWYV RNAs, and we have used it to build a three-dimensional model of the PRLV pseudoknot with a four-nucleotide deletion. The resulting structure defines a minimal RNA pseudoknot motif composed of 22 nucleotides capable of stimulating -1-type ribosomal frameshifts.

  19. Novel missense mutations in a conserved loop between ERCC6 (CSB) helicase motifs V and VI: Insights into Cockayne syndrome.

    PubMed

    Wilson, Brian T; Lochan, Anneline; Stark, Zornitza; Sutton, Ruth E

    2016-03-01

    Cockayne syndrome is caused by biallelic ERCC8 (CSA) or ERCC6 (CSB) mutations and is characterized by growth restriction, microcephaly, developmental delay, and premature pathological aging. Typically affected patients also have dermal photosensitivity. Although Cockayne syndrome is considered a DNA repair disorder, patients with UV-sensitive syndrome, with ERCC8 (CSA) or ERCC6 (CSB) mutations have indistinguishable DNA repair defects, but none of the extradermal features of Cockayne syndrome. We report novel missense mutations affecting a conserved loop in the ERCC6 (CSB) protein, associated with the Cockayne syndrome phenotype. Indeed, the amino acid sequence of this loop is more highly conserved than the adjacent helicase motifs V and VI, suggesting that this is a crucial structural component of the SWI/SNF family of proteins, to which ERCC6 (CSB) belongs. These comprise two RecA-like domains, separated by an interdomain linker, which interact through helicase motif VI. As the observed mutations are likely to act through destabilizing the tertiary protein structure, this prompted us to re-evaluate ERCC6 (CSB) mutation data in relation to the structure of SWI/SNF proteins. Our analysis suggests that antimorphic mutations cause Cockayne syndrome and that biallelic interdomain linker deletions produce more severe phenotypes. Based on our observations, we propose that further investigation of the pathogenic mechanisms underlying Cockayne syndrome should focus on the effect of antimorphic rather than null ERCC6 (CSB) mutations. PMID:26749132

  20. Human podocytes adhere to the KRGDS motif of the alpha3alpha4alpha5 collagen IV network.

    PubMed

    Borza, Corina M; Borza, Dorin-Bogdan; Pedchenko, Vadim; Saleem, Moin A; Mathieson, Peter W; Sado, Yoshikazu; Hudson, Heather M; Pozzi, Ambra; Saus, Juan; Abrahamson, Dale R; Zent, Roy; Hudson, Billy G

    2008-04-01

    Podocyte adhesion to the glomerular basement membrane is required for proper function of the glomerular filtration barrier. However, the mechanism whereby podocytes adhere to collagen IV networks, a major component of the glomerular basement membrane, is poorly understood. The predominant collagen IV network is composed of triple helical protomers containing the alpha3alpha4alpha5 chains. The protomers connect via the trimeric noncollagenous (NC1) domains to form hexamers at the interface. Because the NC1 domains of this network can potentially support integrin-dependent cell adhesion, it was determined whether individual NC1 monomers or alpha3alpha4alpha5 hexamers support podocyte adhesion. It was found that, although human podocytes did not adhere to NC1 domains proper, they did adhere via integrin alphavbeta3 to a KRGDS motif located adjacent to alpha3NC1 domains. Because the KRGDS motif is a site of phosphorylation, its interactions with integrin alphavbeta3 may play a critical role in cell signaling in physiologic and pathologic states. PMID:18235087

  1. A Logical OR Redundancy Within the Asx-Pro-Asx-Gly Type I beta-Turn Motif

    SciTech Connect

    Lee,J.; Dubey, V.; Longo, L.; Blaber, M.

    2008-01-01

    Turn secondary structure is essential to the formation of globular protein architecture. Turn structures are, however, much more complex than either ?-helix or ?-sheet, and the thermodynamics and folding kinetics are poorly understood. Type I ?-turns are the most common type of reverse turn, and they exhibit a statistical consensus sequence of Asx-Pro-Asx-Gly (where Asx is Asp or Asn). A comprehensive series of individual and combined Asx mutations has been constructed within three separate type I 3:5 G1 bulge ?-turns in human fibroblast growth factor-1, and their effects on structure, stability, and folding have been determined. The results show a fundamental logical OR relationship between the Asx residues in the motif, involving H-bond interactions with main-chain amides within the turn. These interactions can be modulated by additional interactions with residues adjacent to the turn at positions i + 4 and i + 6. The results show that the Asx residues in the turn motif make a substantial contribution to the overall stability of the protein, and the Asx logical OR relationship defines a redundant system that can compensate for deleterious point mutations. The results also show that the stability of the turn is unlikely to be the prime determinant of formation of turn structure in the folding transition state.

  2. A Logical OR Redundancy within the Asx-Pro-Asx-Gly Type 1 {Beta}-Turn Motif

    SciTech Connect

    Lee, Jihun; Dubey, Vikash Kumar; Longo, Lian M.; Blaber, Michael

    2008-04-19

    Turn secondary structure is essential to the formation of globular protein architecture. Turn structures are, however, much more complex than either {alpha}-helix or {beta}-sheet, and the thermodynamics and folding kinetics are poorly understood. Type I {beta}-turns are the most common type of reverse turn, and they exhibit a statistical consensus sequence of Asx-Pro-Asx-Gly (where Asx is Asp or Asn). A comprehensive series of individual and combined Asx mutations has been constructed within three separate type I 3:5 G1 bulge {beta}-turns in human fibroblast growth factor-1, and their effects on structure, stability, and folding have been determined. The results show a fundamental logical OR relationship between the Asx residues in the motif, involving H-bond interactions with main-chain amides within the turn. These interactions can be modulated by additional interactions with residues adjacent to the turn at positions i + 4 and i + 6. The results show that the Asx residues in the turn motif make a substantial contribution to the overall stability of the protein, and the Asx logical OR relationship defines a redundant system that can compensate for deleterious point mutations. The results also show that the stability of the turn is unlikely to be the prime determinant of formation of turn structure in the folding transition state.

  3. Fine Scale Analysis of Crossover and Non-Crossover and Detection of Recombination Sequence Motifs in the Honeybee (Apis mellifera)

    PubMed Central

    Bessoltane, Nadia; Toffano-Nioche, Claire; Solignac, Michel; Mougel, Florence

    2012-01-01

    Background Meiotic exchanges are non-uniformly distributed across the genome of most studied organisms. This uneven distribution suggests that recombination is initiated by specific signals and/or regulations. Some of these signals were recently identified in humans and mice. However, it is unclear whether or not sequence signals are also involved in chromosomal recombination of insects. Methodology We analyzed recombination frequencies in the honeybee, in which genome sequencing provided a large amount of SNPs spread over the entire set of chromosomes. As the genome sequences were obtained from a pool of haploid males, which were the progeny of a single queen, an oocyte method (study of recombination on haploid males that develop from unfertilized eggs and hence are the direct reflect of female gametes haplotypes) was developed to detect recombined pairs of SNP sites. Sequences were further compared between recombinant and non-recombinant fragments to detect recombination-specific motifs. Conclusions Recombination events between adjacent SNP sites were detected at an average distance of 92 bp and revealed the existence of high rates of recombination events. This study also shows the presence of conversion without crossover (i. e. non-crossover) events, the number of which largely outnumbers that of crossover events. Furthermore the comparison of sequences that have undergone recombination with sequences that have not, led to the discovery of sequence motifs (CGCA, GCCGC, CCGCA), which may correspond to recombination signals. PMID:22567142

  4. Gene modules associated with breast cancer distant metastasis-free survival in the PAM50 molecular subtypes

    PubMed Central

    Liu, Rong; Zhang, Wei; Liu, Zhao-Qian; Zhou, Hong-Hao

    2016-01-01

    To identify PAM50 subtype–specific associations between distant metastasis-free survival (DMFS) in breast cancer (BC) patients and gene modules describing potentially targetable oncogenic pathways, a comprehensive analysis evaluating the prognostic efficacy of published gene signatures in 2027 BC patients from 13 studies was conducted. We calculated 21 gene modules and computed hazard ratios (HRs) for DMFS for one-unit increases in module score, with and without adjustment for clinical characteristics. By comparing gene expression to survival outcomes, we derived four subtype-specific prognostic signatures for BC. Univariate and multivariate analyses showed that in the luminal A subgroup, E2F3, PTEN and GGI gene module scores were associated with clinical outcome. In the luminal B tumors, RAS was associated with DMFS and in the basal-like tumors, ER was associated with DMFS. Our defined gene modules predicted high-risk patients in multivariate analyses for the basal-like (HR: 2.19, p=2.5×10−4), luminal A (HR: 3.03, p=7.2×10−5), luminal B (HR: 3.00, p=2.4×10−10) and HER2+ (HR: 5.49, p=9.7×10−10) subgroups. We found that different modules are associated with DMFS in different BC subtypes. The results of this study could help to identify new therapeutic strategies for specific molecular subgroups of BC, and could enhance efforts to improve patient-specific therapy options. PMID:26934123

  5. Characterization of an RNA receptor motif that recognizes a GCGA tetraloop.

    PubMed

    Furukawa, Airi; Maejima, Takaya; Matsumura, Shigeyoshi; Ikawa, Yoshiya

    2016-07-01

    Tertiary interactions between a new RNA motif and RNA tetraloops were analyzed to determine whether this new motif shows preference for a GCGA tetraloop. In the structural context of a ligase ribozyme, this motif discriminated GCGA loop from 3 other tetraloops. The affinity between the GCGA loop and its receptor is strong enough to carry out the ribozyme activity. PMID:26967268

  6. Identifiability and inference of pathway motifs by epistasis analysis.

    PubMed

    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. PMID:23822501

  7. Distance conservation of transcriptional and splicing regulatory motifs

    NASA Astrophysics Data System (ADS)

    Lu, Jun; Ding, Changjiang

    2012-09-01

    The distance conservation is a new kind of genomic evolutionary conservation. The transcriptional and splicing regulatory k-mer motifs are functionally important DNA sequence elements. We demonstrated that there exist the evolutionarily conservation of the distance between these k-mer pairs in genomic sequences. This kind of conservation is not based on the strict location of bases in genome sequences, and does not depend on excess frequency of occurrence of k-mers. By utilizing the conservation of k-mer distance it is possible to design a non-alignment-based approach to quickly identify transcriptional or splicing regulatory motifs on the genome-wide scale. In this paper we will summarize our previous studies on distance conservation, introduce the method of distance conservation and indicate the prospects of its application.

  8. A new motif for inhibitors of geranylgeranyl diphosphate synthase.

    PubMed

    Foust, Benjamin J; Allen, Cheryl; Holstein, Sarah A; Wiemer, David F

    2016-08-15

    The enzyme geranylgeranyl diphosphate synthase (GGDPS) is believed to receive the substrate farnesyl diphosphate through one lipophilic channel and release the product geranylgeranyl diphosphate through another. Bisphosphonates with two isoprenoid chains positioned on the α-carbon have proven to be effective inhibitors of this enzyme. Now a new motif has been prepared with one isoprenoid chain on the α-carbon, a second included as a phosphonate ester, and the potential for a third at the α-carbon. The pivaloyloxymethyl prodrugs of several compounds based on this motif have been prepared and the resulting compounds have been tested for their ability to disrupt protein geranylgeranylation and induce cytotoxicity in myeloma cells. The initial biological studies reveal activity consistent with GGDPS inhibition, and demonstrate a structure-function relationship which is dependent on the nature of the alkyl group at the α-carbon. PMID:27338660

  9. Identifiability and inference of pathway motifs by epistasis analysis

    NASA Astrophysics Data System (ADS)

    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.

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

    SciTech Connect

    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.

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

    SciTech Connect

    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.

  12. Biosynthesis of caffeine underlying the diversity of motif B' methyltransferase.

    PubMed

    Nakayama, Fumiyo; Mizuno, Kouichi; Kato, Misako

    2015-05-01

    Caffeine (1,3,7-trimethylxanthine) and theobromine (3,7-dimethylxanthine) are well-known purine alkaloids in Camellia, Coffea, Cola, Paullinia, Ilex, and Theobroma spp. The caffeine biosynthetic pathway depends on the substrate specificity of N-methyltransferases, which are members of the motif B' methyl-transferase family. The caffeine biosynthetic pathways in purine alkaloid-containing plants might have evolved in parallel with one another, consistent with different catalytic properties of the enzymes involved in these pathways. PMID:26058161

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

    NASA Astrophysics Data System (ADS)

    Baskerville, Kim; Grassberger, Peter; Paczuski, Maya

    2007-09-01

    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 , 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 superexponential). 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 tandem affinity purification (TAP) 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 antimotifs ( Z scores <-10 ) when the null model is the ensemble of networks with fixed degree sequence. Strong differences appear between the two networks, with dominant motifs in E. coli being (nearly) bipartite graphs and having many pairs of nodes that connect to the same neighbors, while dominant motifs in yeast tend towards completeness or contain large cliques. We also explore a number of methods that do not rely on measurements of Z scores or comparisons with null models. For instance, we discuss the influence of specific complexes like the 26S proteasome in yeast, where a small number of complexes dominate the k cores with large k and have a decisive effect on the strongest motifs with 6-8 nodes. We also present Zipf plots of counts versus rank. They show broad distributions that are not power laws, in contrast to the case when disconnected subgraphs are included.

  14. 7. VIEW OF WATER TREATMENT PLANT, ADJACENT TO THE COAL ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    7. VIEW OF WATER TREATMENT PLANT, ADJACENT TO THE COAL CONVEYOR; IN THE DISTANCE IS THE FREQUENCY CHANGER HOUSE, WHICH IS ATTACHED TO SWITCH HOUSE NO. 1; LOOKING WEST. - Commonwealth Electric Company, Fisk Street Electrical Generating Station, 1111 West Cermak Avenue, Chicago, Cook County, IL

  15. Colposcopy of vaginal and vulvar human papillomavirus and adjacent sites.

    PubMed

    Hatch, K

    1993-03-01

    Human papillomaviral infections can affect the entire lower female genital tract as multifocal or multicentric disease as well as the surrounding anatomic and adjacent sites. The traditional colposcopic methods are necessary to assist in the diagnosis and help differentiate these infections from other disease mimics. PMID:8392676

  16. Biogeochemistry of hydrothermally and adjacent non-altered soils

    Technology Transfer Automated Retrieval System (TEKTRAN)

    As a field/lab project, students in the Soil Biogeochemistry class of the University of Nevada, Reno described and characterized seven pedons, developed in hydrothermally and adjacent non-hydrothermally altered andesitic parent material near Reno, NV. Hydrothermally altered soils had considerably lo...

  17. 22. Float located adjacent to entry stair in filtration bed. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    22. Float located adjacent to entry stair in filtration bed. The float actuates a valve that maintains water level over the bed. - Lake Whitney Water Filtration Plant, Filtration Plant, South side of Armory Street between Edgehill Road & Whitney Avenue, Hamden, New Haven County, CT

  18. 2. VIEW FROM ROOFTOP OF BUILDING (MOTEL) ADJACENT TO TECHWOOD ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    2. VIEW FROM ROOFTOP OF BUILDING (MOTEL) ADJACENT TO TECHWOOD HOMES, LOOKING WEST. GEORGIA TECH DORMITORY BUILDING, 581-587 TECHWOOD DRIVE, IN FOREGROUND. - Techwood Homes (Public Housing), Bounded by North Avenue, Parker Street, William Street & Lovejoy Street, Atlanta, Fulton County, GA

  19. 10. Detail and contextual view of bridge and adjacent farmstead ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    10. Detail and contextual view of bridge and adjacent farmstead setting. Note laced vertical compression members, latticed portal strut, decorative strut bracing, and lightness of diagonal and lateral tension members. View to southeast through southeast portal from truss mid-span. - Red Bank Creek Bridge, Spanning Red Bank Creek at Rawson Road, Red Bluff, Tehama County, CA

  20. LEHR NO. 2 AND LEHR NO. 3 ADJACENT TO FURNACE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    LEHR NO. 2 AND LEHR NO. 3 ADJACENT TO FURNACE ROOM; THE PIPES AT THE BOTTOM ARE PART OF THE RADIANT HEATING SYSTEM USED FOR HEATING THE FACTORY DURING COLD WEATHER. - Westmoreland Glass Company, Seventh & Kier Streets, Grapeville, Westmoreland County, PA

  1. Effects on stink bugs of field edges adjacent to woodland

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Producers face significant crop losses from stink bug species in the southeastern USA, but the high mobility and polyphagy of the bugs make predictions of their presence in crops difficult. While there is some evidence that they colonize crops from adjacent crops, there are no studies of their colo...

  2. VIEW FROM ATOP ADJACENT RESIDENTIAL TOWER, SHOWING INTERSECTION OF ACACIA ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    VIEW FROM ATOP ADJACENT RESIDENTIAL TOWER, SHOWING INTERSECTION OF ACACIA ROAD WITH BIRCH CIRCLE. VIEW FACING NORTHEAST - Camp H.M. Smith and Navy Public Works Center Manana Title VII (Capehart) Housing, Intersection of Acacia Road and Brich Circle, Pearl City, Honolulu County, HI

  3. VIEW FROM ATOP ADJACENT RESIDENTIAL TOWER, SHOWING RECREATION AREA AND ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    VIEW FROM ATOP ADJACENT RESIDENTIAL TOWER, SHOWING RECREATION AREA AND ENTRY TO NEIGHBORHOOD. VIEW FACING SOUTHEAST - Camp H.M. Smith and Navy Public Works Center Manana Title VII (Capehart) Housing, Intersection of Acacia Road and Brich Circle, Pearl City, Honolulu County, HI

  4. VIEW FROM ATOP ADJACENT RESIDENTIAL TOWER, SHOWING WESTERN SIDE OF ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    VIEW FROM ATOP ADJACENT RESIDENTIAL TOWER, SHOWING WESTERN SIDE OF NEIGHBORHOOD. VIEW FACING NORTHWEST - Camp H.M. Smith and Navy Public Works Center Manana Title VII (Capehart) Housing, Intersection of Acacia Road and Brich Circle, Pearl City, Honolulu County, HI

  5. VIEW FROM ATOP ADJACENT RESIDENTIAL TOWER, SHOWING RECREATION AREA ON ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    VIEW FROM ATOP ADJACENT RESIDENTIAL TOWER, SHOWING RECREATION AREA ON RIGHT, AND HOUSING AREA ON LEFT. VIEW FACING EAST/NORTHEAST - Camp H.M. Smith and Navy Public Works Center Manana Title VII (Capehart) Housing, Intersection of Acacia Road and Brich Circle, Pearl City, Honolulu County, HI

  6. How subaerial salt extrusions influence water quality in adjacent aquifers

    NASA Astrophysics Data System (ADS)

    Mehdizadeh, Razieh; Zarei, Mehdi; Raeisi, Ezzat

    2015-12-01

    Brines supplied from salt extrusions cause significant groundwater salinization in arid and semi-arid regions where salt rock is exposed to dissolution by episodic rainfalls. Here we focus on 62 of the 122 diapirs of Hormuz salt emergent in the southern Iran. To consider managing the degradation effect that salt extrusions have on the quality of adjoining aquifers, it is first necessary to understand how they influence adjacent water resources. We evaluate here the impacts that these diapirs have on adjacent aquifers based on investigating their geomorphologies, geologies, hydrologies and hydrogeologies. The results indicate that 28/62 (45%) of our sample of salt diapirs have no significant impact on the quality of groundwater in adjoining aquifers (namely Type N), while the remaining 34/62 (55%) degrade nearby groundwater quality. We offer simple conceptual models that account for how brines flowing from each of these types of salt extrusions contaminate adjacent aquifers. We identify three main mechanisms that lead to contamination: surface impact (Type A), subsurface intrusion (Type B) and indirect infiltration (Type C). A combination of all these mechanisms degrades the water quality in nearby aquifers in 19/62 (31%) of the salt diapirs studied. Having characterized the mechanism(s) by which each diapir affects the adjacent aquifer, we suggest a few possible remediation strategies to be considered. For instance, engineering the surface runoff of diapirs Types A and C into nearby evaporation basins would improve groundwater quality.

  7. 45. 1915 CLOTH ROOM ADJACENT TO PICKER ROOM, SECOND FLOOR, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    45. 1915 CLOTH ROOM ADJACENT TO PICKER ROOM, SECOND FLOOR, NORTH END OF MILL NO. 2, WALL ON LEFT DIVIDING CLOTH ROOM ADDED LATER (PROBABLY C. 1970s). - Prattville Manufacturing Company, Number One, 242 South Court Street, Prattville, Autauga County, AL

  8. Detail of north intermediate abutment pylon showing proximity of adjacent ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Detail of north intermediate abutment pylon showing proximity of adjacent 1001-1007 East First Street (James K. Hill and Sons Pickle Works Building), facing east - First Street Bridge, Spanning Los Angeles River at First Street, Los Angeles, Los Angeles County, CA

  9. 8. Exterior view, showing tank and associated piping adjacent to ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    8. Exterior view, showing tank and associated piping adjacent to Test Cell 6, Systems Integration Laboratory Building (T-28), looking south. - Air Force Plant PJKS, Systems Integration Laboratory, Systems Integration Laboratory Building, Waterton Canyon Road & Colorado Highway 121, Lakewood, Jefferson County, CO

  10. 4. REAR ELEVATION, DETAIL OF CONSTRUCTION, ADJACENT CORNER POSTS BETWEEN ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4. REAR ELEVATION, DETAIL OF CONSTRUCTION, ADJACENT CORNER POSTS BETWEEN BUILDING PERIODS 1 AND 3. NOTE REUSED WOOD STRIP NAILED TO BUILDING PERIOD 1 POST INSCRIBED 'ST. LEONARD'. THERE ARE NO NAIL HOLES IN THE PERIOD 3 POST, THE FARRING STRIPS ADJUST FOR CLADDING - Charles' Gift, State Routes 2 & 4, Lusby, Calvert County, MD

  11. 1. OVERVIEW SHOWING FIRING CONTROL BLOCKHOUSE 0502 AND ADJACENT OBSERVATION ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. OVERVIEW SHOWING FIRING CONTROL BLOCKHOUSE 0502 AND ADJACENT OBSERVATION TOWER. WATER BRAKE TROUGH SEGMENT AT LOWER RIGHT. Looking north northeast. - Edwards Air Force Base, South Base Sled Track, Firing & Control Blockhouse for 10,000-foot Track, South of Sled Track at midpoint of 20,000-foot track, Lancaster, Los Angeles County, CA

  12. 4. Elevation looking southwest from adjacent hills on northeast side ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4. Elevation looking southwest from adjacent hills on northeast side of bridge, taken from river level. Note entire east side and substructure. - Presumpscot Falls Bridge, Spanning Presumptscot River at Allen Avenue extension, 0.75 mile west of U.S. Interstate 95, Falmouth, Cumberland County, ME

  13. 49 CFR 236.404 - Signals at adjacent control points.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Signals at adjacent control points. 236.404 Section 236.404 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RULES, STANDARDS, AND INSTRUCTIONS GOVERNING THE INSTALLATION, INSPECTION, MAINTENANCE, AND REPAIR...

  14. 12. LOG FOUNDATION ELEMENTS OF THE SAWMILL ADJACENT TO THE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    12. LOG FOUNDATION ELEMENTS OF THE SAWMILL ADJACENT TO THE CANAL, LOOKING EAST. BARREN AREA IN FOREGROUND IS DECOMPOSING SAWDUST. DIRT PILE IN BACKGROUND IS THE EDGE OF THE SUMMIT COUNTY LANDFILL. - Snake River Ditch, Headgate on north bank of Snake River, Dillon, Summit County, CO

  15. A Monte Carlo-based framework enhances the discovery and interpretation of regulatory sequence motifs

    PubMed Central

    2012-01-01

    Background Discovery of functionally significant short, statistically overrepresented subsequence patterns (motifs) in a set of sequences is a challenging problem in bioinformatics. Oftentimes, not all sequences in the set contain a motif. These non-motif-containing sequences complicate the algorithmic discovery of motifs. Filtering the non-motif-containing sequences from the larger set of sequences while simultaneously determining the identity of the motif is, therefore, desirable and a non-trivial problem in motif discovery research. Results We describe MotifCatcher, a framework that extends the sensitivity of existing motif-finding tools by employing random sampling to effectively remove non-motif-containing sequences from the motif search. We developed two implementations of our algorithm; each built around a commonly used motif-finding tool, and applied our algorithm to three diverse chromatin immunoprecipitation (ChIP) data sets. In each case, the motif finder with the MotifCatcher extension demonstrated improved sensitivity over the motif finder alone. Our approach organizes candidate functionally significant discovered motifs into a tree, which allowed us to make additional insights. In all cases, we were able to support our findings with experimental work from the literature. Conclusions Our framework demonstrates that additional processing at the sequence entry level can significantly improve the performance of existing motif-finding tools. For each biological data set tested, we were able to propose novel biological hypotheses supported by experimental work from the literature. Specifically, in Escherichia coli, we suggested binding site motifs for 6 non-traditional LexA protein binding sites; in Saccharomyces cerevisiae, we hypothesize 2 disparate mechanisms for novel binding sites of the Cse4p protein; and in Halobacterium sp. NRC-1, we discoverd subtle differences in a general transcription factor (GTF) binding site motif across several data sets. We

  16. Linear motifs confer functional diversity onto splice variants

    PubMed Central

    Weatheritt, Robert J.; Davey, Norman E.; Gibson, Toby J.

    2012-01-01

    The pre-translational modification of messenger ribonucleic acids (mRNAs) by alternative promoter usage and alternative splicing is an important source of pleiotropy. Despite intensive efforts, our understanding of the functional implications of this dynamically created diversity is still incomplete. Using the available knowledge of interaction modules, particularly within intrinsically disordered regions (IDRs), we analysed the occurrences of protein modules within alternative exons. We find that regions removed or included by pre-translational variation are enriched in linear motifs suggesting that the removal or inclusion of exons containing these interaction modules is an important regulatory mechanism. In particular, we observe that PDZ-, PTB-, SH2- and WW-domain binding motifs are more likely to occur within alternative exons. We also determine that regions removed or included by alternative promoter usage are enriched in IDRs suggesting that protein isoform diversity is tightly coupled to the modulation of IDRs. This study, therefore, demonstrates that short linear motifs are key components for establishing protein diversity between splice variants. PMID:22638587

  17. Structure and ubiquitin binding of the ubiquitin-interacting motif

    SciTech Connect

    Fisher,R.; Wang, B.; Alam, S.; Higginson, D.; Robinson, H.; Sundquist, C.; Hill, C.

    2003-01-01

    Ubiquitylation is used to target proteins into a large number of different biological processes including proteasomal degradation, endocytosis, virus budding, and vacuolar protein sorting (Vps). Ubiquitylated proteins are typically recognized using one of several different conserved ubiquitin binding modules. Here, we report the crystal structure and ubiquitin binding properties of one such module, the ubiquitin-interacting motif (UIM). We found that UIM peptides from several proteins involved in endocytosis and vacuolar protein sorting including Hrs, Vps27p, Stam1, and Eps15 bound specifically, but with modest affinity (K{sub d} = 0.1-1 mM), to free ubiquitin. Full affinity ubiquitin binding required the presence of conserved acidic patches at the N and C terminus of the UIM, as well as highly conserved central alanine and serine residues. NMR chemical shift perturbation mapping experiments demonstrated that all of these UIM peptides bind to the I44 surface of ubiquitin. The 1.45 {angstrom} resolution crystal structure of the second yeast Vps27p UIM (Vps27p-2) revealed that the ubiquitin-interacting motif forms an amphipathic helix. Although Vps27p-2 is monomeric in solution, the motif unexpectedly crystallized as an antiparallel four-helix bundle, and the potential biological implications of UIM oligomerization are therefore discussed.

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

    DOEpatents

    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. TOPDOM: database of conservatively located domains and motifs in proteins

    PubMed Central

    Varga, Julia; Dobson, László; Tusnády, Gábor E.

    2016-01-01

    Summary: The TOPDOM database—originally created as a collection of domains and motifs located consistently on the same side of the membranes in α-helical transmembrane proteins—has been updated and extended by taking into consideration consistently localized domains and motifs in globular proteins, too. By taking advantage of the recently developed CCTOP algorithm to determine the type of a protein and predict topology in case of transmembrane proteins, and by applying a thorough search for domains and motifs as well as utilizing the most up-to-date version of all source databases, we managed to reach a 6-fold increase in the size of the whole database and a 2-fold increase in the number of transmembrane proteins. Availability and implementation: TOPDOM database is available at http://topdom.enzim.hu. The webpage utilizes the common Apache, PHP5 and MySQL software to provide the user interface for accessing and searching the database. The database itself is generated on a high performance computer. Contact: tusnady.gabor@ttk.mta.hu. Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27153630

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

    PubMed

    Davies, Toby; Marchione, Elio

    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

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

    NASA Astrophysics Data System (ADS)

    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.

  2. Event Networks and the Identification of Crime Pattern Motifs

    PubMed Central

    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

  3. GxxxG motifs hold the TIM23 complex together.

    PubMed

    Demishtein-Zohary, Keren; Marom, Milit; Neupert, Walter; Mokranjac, Dejana; Azem, Abdussalam

    2015-06-01

    Approximately 99% of the mitochondrial proteome is nucleus-encoded, synthesized in the cytosol, and subsequently imported into and sorted to the correct compartment in the organelle. The translocase of the inner mitochondrial membrane 23 (TIM23) complex is the major protein translocase of the inner membrane, and is responsible for translocation of proteins across the inner membrane and their insertion into the inner membrane. Tim23 is the central component of the complex that forms the import channel. A high-resolution structure of the import channel is still missing, and structural elements important for its function are unknown. In the present study, we analyzed the importance of the highly abundant GxxxG motifs in the transmembrane segments of Tim23 for the structural integrity of the TIM23 complex. Of 10 glycines present in the GxxxG motifs in the first, second and third transmembrane segments of Tim23, mutations of three of them in transmembrane segments 1 and 2 resulted in a lethal phenotype, and mutations of three others in a temperature-sensitive phenotype. The remaining four caused no obvious growth phenotype. Importantly, none of the mutations impaired the import and membrane integration of Tim23 precursor into mitochondria. However, the severity of growth impairment correlated with the destabilization of the TIM23 complex. We conclude that the GxxxG motifs found in the first and second transmembrane segments of Tim23 are necessary for the structural integrity of the TIM23 complex. PMID:25765297

  4. QuateXelero: An Accelerated Exact Network Motif Detection Algorithm

    PubMed Central

    Khakabimamaghani, Sahand; Sharafuddin, Iman; Dichter, Norbert; Koch, Ina; Masoudi-Nejad, Ali

    2013-01-01

    Finding motifs in biological, social, technological, and other types of networks has become a widespread method to gain more knowledge about these networks’ structure and function. However, this task is very computationally demanding, because it is highly associated with the graph isomorphism which is an NP problem (not known to belong to P or NP-complete subsets yet). Accordingly, this research is endeavoring to decrease the need to call NAUTY isomorphism detection method, which is the most time-consuming step in many existing algorithms. The work provides an extremely fast motif detection algorithm called QuateXelero, which has a Quaternary Tree data structure in the heart. The proposed algorithm is based on the well-known ESU (FANMOD) motif detection algorithm. The results of experiments on some standard model networks approve the overal superiority of the proposed algorithm, namely QuateXelero, compared with two of the fastest existing algorithms, G-Tries and Kavosh. QuateXelero is especially fastest in constructing the central data structure of the algorithm from scratch based on the input network. PMID:23874498

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

    PubMed

    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. PMID:26475923

  6. QuateXelero: an accelerated exact network motif detection algorithm.

    PubMed

    Khakabimamaghani, Sahand; Sharafuddin, Iman; Dichter, Norbert; Koch, Ina; Masoudi-Nejad, Ali

    2013-01-01

    Finding motifs in biological, social, technological, and other types of networks has become a widespread method to gain more knowledge about these networks' structure and function. However, this task is very computationally demanding, because it is highly associated with the graph isomorphism which is an NP problem (not known to belong to P or NP-complete subsets yet). Accordingly, this research is endeavoring to decrease the need to call NAUTY isomorphism detection method, which is the most time-consuming step in many existing algorithms. The work provides an extremely fast motif detection algorithm called QuateXelero, which has a Quaternary Tree data structure in the heart. The proposed algorithm is based on the well-known ESU (FANMOD) motif detection algorithm. The results of experiments on some standard model networks approve the overal superiority of the proposed algorithm, namely QuateXelero, compared with two of the fastest existing algorithms, G-Tries and Kavosh. QuateXelero is especially fastest in constructing the central data structure of the algorithm from scratch based on the input network. PMID:23874498

  7. CCL20/macrophage inflammatory protein 3alpha and tumor necrosis factor alpha production by primary uterine epithelial cells in response to treatment with lipopolysaccharide or Pam3Cys.

    PubMed

    Crane-Godreau, Mardi A; Wira, Charles R

    2005-01-01

    Having previously shown that CCL20/macrophage inflammatory protein 3alpha and tumor necrosis factor alpha (TNF-alpha) are released by polarized primary rat uterine epithelial cells (UEC) in response to Escherichia coli but not to Lactobacillus rhamnosus, we sought to determine if epithelial cells are responsive to pathogen-associated molecular patterns (PAMP), including lipopolysaccharide (LPS), lipoteichoic acid (LTA), and Pam(3)Cys, a bacterial lipoprotein analog. Epithelial cells were grown to confluence on Nunc cell culture inserts prior to apical treatment with PAMPs. In response to LPS, LTA, and Pam(3)Cys (EMC Microcollection GmbH, Tubingen, Germany), CCL20 levels increased (4- to 10-fold) while PAMPs caused increased TNF-alpha (1- to 4-fold) in the medium collected after 24 h of incubation. Both apical and basolateral secretion of CCL20 and TNF-alpha increased in response to PAMPs, but treatments had no effect on cell viability and integrity, as measured by transepithelial resistance. Time course studies of CCL20 and TNF-alpha release in response to Pam(3)Cys and LPS indicated that CCL20 release peaked between 2 and 4 h after treatment, whereas TNF-alpha release was gradual over the length of the incubation. Freeze-thaw and cell lysis experiments, along with actinomycin D studies, suggested that CCL20 and TNF-alpha are synthesized in response to PAMP stimulation. Taken together, these studies demonstrate that E. coli and selected PAMPs have direct effects on the production of CCL20 and TNF-alpha without affecting cell integrity. Since CCL20 is known to be both chemotactic and antimicrobial, the increase in apical and basolateral release by UEC in response to PAMPs suggests a new mechanism of innate immune protection in the female reproductive tract. PMID:15618187

  8. Multiple Weak Linear Motifs Enhance Recruitment and Processivity in SPOP-Mediated Substrate Ubiquitination.

    PubMed

    Pierce, Wendy K; Grace, Christy R; Lee, Jihun; Nourse, Amanda; Marzahn, Melissa R; Watson, Edmond R; High, Anthony A; Peng, Junmin; Schulman, Brenda A; Mittag, Tanja

    2016-03-27

    Primary sequence motifs, with millimolar affinities for binding partners, are abundant in disordered protein regions. In multivalent interactions, such weak linear motifs can cooperate to recruit binding partners via avidity effects. If linear motifs recruit modifying enzymes, optimal placement of weak motifs may regulate access to modification sites. Weak motifs may thus exert physiological relevance stronger than that suggested by their affinities, but molecular mechanisms of their function are still poorly understood. Herein, we use the N-terminal disordered region of the Hedgehog transcriptional regulator Gli3 (Gli3(1-90)) to determine the role of weak motifs encoded in its primary sequence for the recruitment of its ubiquitin ligase CRL3(SPOP) and the subsequent effect on ubiquitination efficiency. The substrate adaptor SPOP binds linear motifs through its MATH (meprin and TRAF homology) domain and forms higher-order oligomers through its oligomerization domains, rendering SPOP multivalent for its substrates. Gli3 has multiple weak SPOP binding motifs. We map three such motifs in Gli3(1-90), the weakest of which has a millimolar dissociation constant. Multivalency of ligase and substrate for each other facilitates enhanced ligase recruitment and stimulates Gli3(1-90) ubiquitination in in vitro ubiquitination assays. We speculate that the weak motifs enable processivity through avidity effects and by providing steric access to lysine residues that are otherwise not prioritized for polyubiquitination. Weak motifs may generally be employed in multivalent systems to act as gatekeepers regulating post-translational modification. PMID:26475525

  9. A Novel Alignment-Free Method for Comparing Transcription Factor Binding Site Motifs

    PubMed Central

    Xu, Minli; Su, Zhengchang

    2010-01-01

    Background Transcription factor binding site (TFBS) motifs can be accurately represented by position frequency matrices (PFM) or other equivalent forms. We often need to compare TFBS motifs using their PFMs in order to search for similar motifs in a motif database, or cluster motifs according to their binding preference. The majority of current methods for motif comparison involve a similarity metric for column-to-column comparison and a method to find the optimal position alignment between the two compared motifs. In some applications, alignment-free methods might be preferred; however, few such methods with high accuracy have been described. Methodology/Principal Findings Here we describe a novel alignment-free method for quantifying the similarity of motifs using their PFMs by converting PFMs into k-mer vectors. The motifs could then be compared by measuring the similarity among their corresponding k-mer vectors. Conclusions/Significance We demonstrate that our method in general achieves similar performance or outperforms the existing methods for clustering motifs according to their binding preference and identifying similar motifs of transcription factors of the same family. PMID:20098703

  10. Motif-based analysis of large nucleotide data sets using MEME-ChIP

    PubMed Central

    Ma, Wenxiu; Noble, William S; Bailey, Timothy L

    2014-01-01

    MEME-ChIP is a web-based tool for analyzing motifs in large DNA or RNA data sets. It can analyze peak regions identified by ChIP-seq, cross-linking sites identified by cLIP-seq and related assays, as well as sets of genomic regions selected using other criteria. MEME-ChIP performs de novo motif discovery, motif enrichment analysis, motif location analysis and motif clustering, providing a comprehensive picture of the DNA or RNA motifs that are enriched in the input sequences. MEME-ChIP performs two complementary types of de novo motif discovery: weight matrix–based discovery for high accuracy; and word-based discovery for high sensitivity. Motif enrichment analysis using DNA or RNA motifs from human, mouse, worm, fly and other model organisms provides even greater sensitivity. MEME-ChIP’s interactive HTML output groups and aligns significant motifs to ease interpretation. this protocol takes less than 3 h, and it provides motif discovery approaches that are distinct and complementary to other online methods. PMID:24853928

  11. Agonist and antagonist switch DNA motifs recognized by human androgen receptor in prostate cancer

    PubMed Central

    Chen, Zhong; Lan, Xun; Thomas-Ahner, Jennifer M; Wu, Dayong; Liu, Xiangtao; Ye, Zhenqing; Wang, Liguo; Sunkel, Benjamin; Grenade, Cassandra; Chen, Junsheng; Zynger, Debra L; Yan, Pearlly S; Huang, Jiaoti; Nephew, Kenneth P; Huang, Tim H-M; Lin, Shili; Clinton, Steven K; Li, Wei; Jin, Victor X; Wang, Qianben

    2015-01-01

    Human transcription factors recognize specific DNA sequence motifs to regulate transcription. It is unknown whether a single transcription factor is able to bind to distinctly different motifs on chromatin, and if so, what determines the usage of specific motifs. By using a motif-resolution chromatin immunoprecipitation-exonuclease (ChIP-exo) approach, we find that agonist-liganded human androgen receptor (AR) and antagonist-liganded AR bind to two distinctly different motifs, leading to distinct transcriptional outcomes in prostate cancer cells. Further analysis on clinical prostate tissues reveals that the binding of AR to these two distinct motifs is involved in prostate carcinogenesis. Together, these results suggest that unique ligands may switch DNA motifs recognized by ligand-dependent transcription factors in vivo. Our findings also provide a broad mechanistic foundation for understanding ligand-specific induction of gene expression profiles. PMID:25535248

  12. Agonist and antagonist switch DNA motifs recognized by human androgen receptor in prostate cancer.

    PubMed

    Chen, Zhong; Lan, Xun; Thomas-Ahner, Jennifer M; Wu, Dayong; Liu, Xiangtao; Ye, Zhenqing; Wang, Liguo; Sunkel, Benjamin; Grenade, Cassandra; Chen, Junsheng; Zynger, Debra L; Yan, Pearlly S; Huang, Jiaoti; Nephew, Kenneth P; Huang, Tim H-M; Lin, Shili; Clinton, Steven K; Li, Wei; Jin, Victor X; Wang, Qianben

    2015-02-12

    Human transcription factors recognize specific DNA sequence motifs to regulate transcription. It is unknown whether a single transcription factor is able to bind to distinctly different motifs on chromatin, and if so, what determines the usage of specific motifs. By using a motif-resolution chromatin immunoprecipitation-exonuclease (ChIP-exo) approach, we find that agonist-liganded human androgen receptor (AR) and antagonist-liganded AR bind to two distinctly different motifs, leading to distinct transcriptional outcomes in prostate cancer cells. Further analysis on clinical prostate tissues reveals that the binding of AR to these two distinct motifs is involved in prostate carcinogenesis. Together, these results suggest that unique ligands may switch DNA motifs recognized by ligand-dependent transcription factors in vivo. Our findings also provide a broad mechanistic foundation for understanding ligand-specific induction of gene expression profiles. PMID:25535248

  13. The MotA transcription factor from bacteriophage T4 contains a novel DNA-binding domain : the 'double wing' motif.

    SciTech Connect

    Li, N.; Sickmier, E. A.; Zhang, R.; Joachimiak, A.; White, S. W.; Biosciences Division; St. Jude Children's Research Hospital; Univ. of Tennessee Health Science Center; Corixa Inc.

    2002-01-01

    MotA is a transcription factor from bacteriophage T4 that helps adapt the host Escherichia coli transcription apparatus to T4 middle promoters. We have determined the crystal structure of the C-terminal DNA-binding domain of MotA (MotCF) to 1.6 A resolution using multiwavelength, anomalous diffraction methods. The structure reveals a novel DNA-binding alpha/beta motif that contains an exposed beta-sheet surface that mediates interactions with the DNA. Independent biochemical experiments have shown that MotCF binds to one surface of a single turn of DNA through interactions in adjacent major and minor grooves. We present a model of the interaction in which beta-ribbons at opposite corners of the six-stranded beta-sheet penetrate the DNA grooves, and call the motif a 'double wing' to emphasize similarities to the 'winged-helix' motif. The model is consistent with data on how MotA functions at middle promoters, and provides an explanation for why MotA can form non-specific multimers on DNA.

  14. JPDI, a novel endoplasmic reticulum-resident protein containing both a BiP-interacting J-domain and thioredoxin-like motifs.

    PubMed

    Hosoda, Akira; Kimata, Yukio; Tsuru, Akio; Kohno, Kenji

    2003-01-24

    Several endoplasmic reticulum (ER)-resident luminal proteins have a characteristic ER retrieval signal, KDEL, or its variants at their C terminus. Our previous work searching EST databases for proteins containing the C-terminal KDEL motif predicted some novel murine proteins, one of which designated JPDI (J-domain-containing protein disulfide isomerase-like protein) is characterized in this study. The primary structure of JPDI is unique, because in addition to a J-domain motif adjacent to the N-terminal translocation signal sequence, four thioredoxin-like motifs were found in a single polypeptide. As examined by Northern blotting, the expression of JPDI was essentially ubiquitous in tissues and almost independent of ER stress. A computational prediction that JPDI is an ER-resident luminal protein was experimentally supported by immunofluorescent staining of epitope-tagged JPDI-expressing cells together with glycosylation and protease protection studies of this protein. JPDI probably acts as a DnaJ-like partner of BiP, because a recombinant protein carrying the J-domain of JPDI associated with BiP in an ATP-dependent manner and enhanced its ATPase activity. We speculate that for the folding of some proteins in the ER, chaperoning by BiP and formation of proper disulfide bonds may synchronously occur in a JPDI-dependent manner. PMID:12446677

  15. A three-dimensional characterization of Arctic aerosols from airborne Sun photometer observations: PAM-ARCMIP, April 2009

    NASA Astrophysics Data System (ADS)

    Stone, R. S.; Herber, A.; Vitale, V.; Mazzola, M.; Lupi, A.; Schnell, R. C.; Dutton, E. G.; Liu, P. S. K.; Li, S.-M.; Dethloff, K.; Lampert, A.; Ritter, C.; Stock, M.; Neuber, R.; Maturilli, M.

    2010-07-01

    The Arctic climate is modulated, in part, by atmospheric aerosols that affect the distribution of radiant energy passing through the atmosphere. Aerosols affect the surface-atmosphere radiation balance directly through interactions with solar and terrestrial radiation and indirectly through interactions with cloud particles. Better quantification of the radiative forcing by different types of aerosol is needed to improve predictions of future climate. During April 2009, the airborne campaign Pan-Arctic Measurements and Arctic Regional Climate Model Inter-comparison Project (PAM-ARCMIP) was conducted. The mission was organized by Alfred Wegener Institute for Polar and Marine Research of Germany and utilized their research aircraft, Polar-5. The goal was to obtain a snapshot of surface and atmospheric conditions over the central Arctic prior to the onset of the melt season. Characterizing aerosols was one objective of the campaign. Standard Sun photometric procedures were adopted to quantify aerosol optical depth AOD, providing a three-dimensional view of the aerosol, which was primarily haze from anthropogenic sources. Independent, in situ measurements of particle size distribution and light extinction, derived from airborne lidar, are used to corroborate inferences made using the AOD results. During April 2009, from the European to the Alaskan Arctic, from sub-Arctic latitudes to near the pole, the atmosphere was variably hazy with total column AOD at 500 nm ranging from ˜0.12 to >0.35, values that are anomalously high compared with previous years. The haze, transported primarily from Eurasian industrial regions, was concentrated within and just above the surface-based temperature inversion layer. Extinction, as measured using an onboard lidar system, was also greatest at low levels, where particles tended to be slightly larger than at upper levels. Black carbon (BC) (soot) was observed at all levels sampled, but at moderate to low concentrations compared with

  16. 38. VIEW OF COTTRELL MAGNETIC IMPULSE GENERATOR ADJACENT TO SIX ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    38. VIEW OF COTTRELL MAGNETIC IMPULSE GENERATOR ADJACENT TO SIX GAP ROTARY RECTIFIER. THIS UNIT GENERATED A MAGNETIC PULSE WHICH WAS TRANSMITTED TO THE COLLECTION PLATES IN THE ELECTROSTATIC PRECIPITATOR CHAMBER. THESE PERIODIC PULSES VIBRATE THE PLATES AND CAUSE PRECIPITATED ARTICLES OF SMOKE AND FLY ASH TO FALL TO THE BOTTOM OF THE PRECIPITATOR CHAMBER. - New York, New Haven & Hartford Railroad, Cos Cob Power Plant, Sound Shore Drive, Greenwich, Fairfield County, CT

  17. Conference room 211, adjacent to commander's quarters, with vault door ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Conference room 211, adjacent to commander's quarters, with vault door at right. Projection area at center is equipped with automatic security drapes. Projection room uses a 45 degree mirror to reflect the image onto the frosted glass screen. Door on far left leads to display area senior battle staff viewing bridge, and the commander's quarters - March Air Force Base, Strategic Air Command, Combat Operations Center, 5220 Riverside Drive, Moreno Valley, Riverside County, CA

  18. Epithelial dysplasia immediately adjacent to oral squamous cell carcinomas.

    PubMed

    Wright, A; Shear, M

    1985-08-01

    A number of workers have attempted to identify dysplastic features which may be predictors of malignant change, by prospective studies of dysplastic lesions. In the present study we have looked at dysplastic changes immediately adjacent to established squamous carcinomas in an attempt to determine whether any predictors can be identified in this way. Eighty cases were included in the study for whom information on tobacco usage was known. Clinical details were recorded. Histological features in epithelium immediately adjacent to the carcinoma were studied in representative sections. Eighteen specific histological characteristics were noted as present or absent. Data were transferred by Conversational Monitoring System (CMS) terminal, processed and analyzed by the Statistical Analysis System (SAS) Computer package. Only 8 patients were non-smokers (10%). Dysplastic changes in adjacent epithelium were frequently multicentric. Changes appear to occur first in the basal layer in the form of disturbance of polarity or basal cell hyperplasia, while other dysplastic features are absent. The feature referred to as basal cell hyperplasia appears, in fact, to represent disturbed epithelial maturation. In 80% of cases increased nucleo-cytoplasmic ratio appears to result from a decrease in cytoplasmic volume rather than increased nuclear size. A defect in RNA synthesis may be a factor. A sharp decrease in inflammatory cells in the lamina propria of adjacent epithelium, compared with that of the carcinoma, was observed. Russell bodies were noted in 5 of the 8 lesions in non-smokers (63%) and in 16 of 72 lesions in smokers (22%) (p less than 0.001; Chi2 17.65). PMID:3928850

  19. 20. Interior view of fuel storage pit or vault adjacent ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    20. Interior view of fuel storage pit or vault adjacent to Test Cell 9 in Component Test Laboratory (T-27), looking west. Photograph shows upgraded instrumentation, piping, tanks, and technological modifications installed in 1997-99 to accommodate component testing requirements for the Atlas V missile. - Air Force Plant PJKS, Systems Integration Laboratory, Components Test Laboratory, Waterton Canyon Road & Colorado Highway 121, Lakewood, Jefferson County, CO

  20. FMRI evidence of acupoints specificity in two adjacent acupoints.

    PubMed

    Liu, Hua; Xu, Jian-Yang; Li, Lin; Shan, Bao-Ci; Nie, Bin-Bin; Xue, Jing-Quan

    2013-01-01

    Objectives. Acupoint specificity is the foundation of acupuncture treatment. The aim of this study is to investigate whether the acupoint specificity exists in two adjacent acupoints. Design and Setting. Two adjacent real acupoints, LR3 (Taichong) and ST44 (Neiting), and a nearby nonacupoint were selected. Thirty-three health volunteers were divided into three groups in random order, and each group only received acupuncture at one of the three points. While they received acupuncture, fMRI scan was performed. Results. The common cerebral activated areas responding to LR3 and ST44 included the contralateral primary somatosensory area (SI) and ipsilateral cerebellum. Acupuncture at LR3 specifically activated contralateral middle occipital gyrus, ipsilateral medial frontal gyrus, superior parietal lobe, middle temporal gyrus, rostral anterior cingulate cortex (rACC), lentiform nucleus, insula, and contralateral thalamus. Stimulation at ST44 selectively activated ipsilateral secondary somatosensory area (SII), contralateral middle frontal gyrus, inferior frontal gyrus, lingual gyrus, lentiform nucleus, and bilateral posterior cingulate cortex (PCC). Conclusions. Acupuncture at adjacent acupoints elicits distinct cerebral activation patterns, and those specific patterns might be involved in the mechanism of the specific therapeutic effects of different acupoints. PMID:23762172

  1. Divergent viral presentation among human tumors and adjacent normal tissues.

    PubMed

    Cao, Song; Wendl, Michael C; Wyczalkowski, Matthew A; Wylie, Kristine; Ye, Kai; Jayasinghe, Reyka; Xie, Mingchao; Wu, Song; Niu, Beifang; Grubb, Robert; Johnson, Kimberly J; Gay, Hiram; Chen, Ken; Rader, Janet S; Dipersio, John F; Chen, Feng; Ding, Li

    2016-01-01

    We applied a newly developed bioinformatics system called VirusScan to investigate the viral basis of 6,813 human tumors and 559 adjacent normal samples across 23 cancer types and identified 505 virus positive samples with distinctive, organ system- and cancer type-specific distributions. We found that herpes viruses (e.g., subtypes HHV4, HHV5, and HHV6) that are highly prevalent across cancers of the digestive tract showed significantly higher abundances in tumor versus adjacent normal samples, supporting their association with these cancers. We also found three HPV16-positive samples in brain lower grade glioma (LGG). Further, recurrent HBV integration at the KMT2B locus is present in three liver tumors, but absent in their matched adjacent normal samples, indicating that viral integration induced host driver genetic alterations are required on top of viral oncogene expression for initiation and progression of liver hepatocellular carcinoma. Notably, viral integrations were found in many genes, including novel recurrent HPV integrations at PTPN13 in cervical cancer. Finally, we observed a set of HHV4 and HBV variants strongly associated with ethnic groups, likely due to viral sequence evolution under environmental influences. These findings provide important new insights into viral roles of tumor initiation and progression and potential new therapeutic targets. PMID:27339696

  2. Osteochondroma of the hip with adjacent bursal chondromatosis.

    PubMed

    Gould, Elaine S; Baker, Kevin S; Huang, Mingqian; Khan, Fazel; Hoda, Syed

    2014-12-01

    It is well established that irregular bursae can form adjacent to an osteochondroma (bursa exostotica) as a result of mechanical irritation and that these bursae can be complicated by inflammation, hemorrhage, or infection. Bursal chondromatosis is a rare complication, with only seven published cases in the literature according to our searches. We present the case of a 53-year-old female who presented with slowly progressive left hip/thigh pain and was found to have an osteochondroma arising from the lesser trochanter with numerous ossified bodies in the adjacent soft tissues. MRI demonstrated osteochondral bodies in a fluid-filled bursa adjacent to the osteochondroma, with several of the bodies noted to be fairly displaced from the osteochondroma cartilaginous cap. At surgery, the osteochondroma was removed and numerous bodies of varying sizes were excised, some of which were noted to be adherent to the bursal lining and others that were separated/distant from the cartilage cap. The question arises as to whether this process represents bursal chondromatosis resulting from benign neoplasia of cells lining the abnormal bursa, "cartilage shedding" from the osteochondromatous cap, or both. The purpose in presenting this case is to introduce a rare complication of an osteochondroma, demonstrate that soft tissue calcification and osteochondral densities displaced from an underlying osteochondroma are not always the result of sarcomatous degeneration, and provide support for the theory that cells lining a bursa in a nonphysiologic location can undergo benign neoplasia with subsequent formation of osteochondral bodies. PMID:25001874

  3. Divergent viral presentation among human tumors and adjacent normal tissues

    PubMed Central

    Cao, Song; Wendl, Michael C.; Wyczalkowski, Matthew A.; Wylie, Kristine; Ye, Kai; Jayasinghe, Reyka; Xie, Mingchao; Wu, Song; Niu, Beifang; Grubb, Robert; Johnson, Kimberly J.; Gay, Hiram; Chen, Ken; Rader, Janet S.; Dipersio, John F.; Chen, Feng; Ding, Li

    2016-01-01

    We applied a newly developed bioinformatics system called VirusScan to investigate the viral basis of 6,813 human tumors and 559 adjacent normal samples across 23 cancer types and identified 505 virus positive samples with distinctive, organ system- and cancer type-specific distributions. We found that herpes viruses (e.g., subtypes HHV4, HHV5, and HHV6) that are highly prevalent across cancers of the digestive tract showed significantly higher abundances in tumor versus adjacent normal samples, supporting their association with these cancers. We also found three HPV16-positive samples in brain lower grade glioma (LGG). Further, recurrent HBV integration at the KMT2B locus is present in three liver tumors, but absent in their matched adjacent normal samples, indicating that viral integration induced host driver genetic alterations are required on top of viral oncogene expression for initiation and progression of liver hepatocellular carcinoma. Notably, viral integrations were found in many genes, including novel recurrent HPV integrations at PTPN13 in cervical cancer. Finally, we observed a set of HHV4 and HBV variants strongly associated with ethnic groups, likely due to viral sequence evolution under environmental influences. These findings provide important new insights into viral roles of tumor initiation and progression and potential new therapeutic targets. PMID:27339696

  4. Using BRDFs for accurate albedo calculations and adjacency effect corrections

    SciTech Connect

    Borel, C.C.; Gerstl, S.A.W.

    1996-09-01

    In this paper the authors discuss two uses of BRDFs in remote sensing: (1) in determining the clear sky top of the atmosphere (TOA) albedo, (2) in quantifying the effect of the BRDF on the adjacency point-spread function and on atmospheric corrections. The TOA spectral albedo is an important parameter retrieved by the Multi-angle Imaging Spectro-Radiometer (MISR). Its accuracy depends mainly on how well one can model the surface BRDF for many different situations. The authors present results from an algorithm which matches several semi-empirical functions to the nine MISR measured BRFs that are then numerically integrated to yield the clear sky TOA spectral albedo in four spectral channels. They show that absolute accuracies in the albedo of better than 1% are possible for the visible and better than 2% in the near infrared channels. Using a simplified extensive radiosity model, the authors show that the shape of the adjacency point-spread function (PSF) depends on the underlying surface BRDFs. The adjacency point-spread function at a given offset (x,y) from the center pixel is given by the integral of transmission-weighted products of BRDF and scattering phase function along the line of sight.

  5. DNA nanotechnology based on i-motif structures.

    PubMed

    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

  6. Genomic analysis of membrane protein families: abundance and conserved motifs

    PubMed Central

    Liu, Yang; Engelman, Donald M; Gerstein, Mark

    2002-01-01

    Background Polytopic membrane proteins can be related to each other on the basis of the number of transmembrane helices and sequence similarities. Building on the Pfam classification of protein domain families, and using transmembrane-helix prediction and sequence-similarity searching, we identified a total of 526 well-characterized membrane protein families in 26 recently sequenced genomes. To this we added a clustering of a number of predicted but unclassified membrane proteins, resulting in a total of 637 membrane protein families. Results Analysis of the occurrence and composition of these families revealed several interesting trends. The number of assigned membrane protein domains has an approximately linear relationship to the total number of open reading frames (ORFs) in 26 genomes studied. Caenorhabditis elegans is an apparent outlier, because of its high representation of seven-span transmembrane (7-TM) chemoreceptor families. In all genomes, including that of C. elegans, the number of distinct membrane protein families has a logarithmic relation to the number of ORFs. Glycine, proline, and tyrosine locations tend to be conserved in transmembrane regions within families, whereas isoleucine, valine, and methionine locations are relatively mutable. Analysis of motifs in putative transmembrane helices reveals that GxxxG and GxxxxxxG (which can be written GG4 and GG7, respectively; see Materials and methods) are among the most prevalent. This was noted in earlier studies; we now find these motifs are particularly well conserved in families, however, especially those corresponding to transporters, symporters, and channels. Conclusions We carried out a genome-wide analysis on patterns of the classified polytopic membrane protein families and analyzed the distribution of conserved amino acids and motifs in the transmembrane helix regions in these families. PMID:12372142

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

    SciTech Connect

    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 patterns in

  8. Identifying combinatorial regulation of transcription factors and binding motifs

    PubMed Central

    Kato, Mamoru; Hata, Naoya; Banerjee, Nilanjana; Futcher, Bruce; Zhang, Michael Q

    2004-01-01

    Background Combinatorial interaction of transcription factors (TFs) is important for gene regulation. Although various genomic datasets are relevant to this issue, each dataset provides relatively weak evidence on its own. Developing methods that can integrate different sequence, expression and localization data have become important. Results Here we use a novel method that integrates chromatin immunoprecipitation (ChIP) data with microarray expression data and with combinatorial TF-motif analysis. We systematically identify combinations of transcription factors and of motifs. The various combinations of TFs involved multiple binding mechanisms. We reconstruct a new combinatorial regulatory map of the yeast cell cycle in which cell-cycle regulation can be drawn as a chain of extended TF modules. We find that the pairwise combination of a TF for an early cell-cycle phase and a TF for a later phase is often used to control gene expression at intermediate times. Thus the number of distinct times of gene expression is greater than the number of transcription factors. We also see that some TF modules control branch points (cell-cycle entry and exit), and in the presence of appropriate signals they can allow progress along alternative pathways. Conclusions Combining different data sources can increase statistical power as demonstrated by detecting TF interactions and composite TF-binding motifs. The original picture of a chain of simple cell-cycle regulators can be extended to a chain of composite regulatory modules: different modules may share a common TF component in the same pathway or a TF component cross-talking to other pathways. PMID:15287978

  9. Bioconjugatable Porphyrins Bearing a Compact Swallowtail Motif for Water Solubility

    PubMed Central

    Borbas, K. Eszter; Mroz, Pawel; Hamblin, Michael R.; Lindsey, Jonathan S.

    2011-01-01

    A broad range of applications requires access to water-soluble, bioconjugatable porphyrins. Branched alkyl groups attached at the branching site to the porphyrin meso position are known to impart high organic solubility. Such “swallowtail” motifs bearing a polar group (hydroxy, dihydroxyphosphoryl, dihydroxyphosphoryloxy) at the terminus of each branch have now been incorporated at a meso site in trans-AB-porphyrins. The incorporation of the swallowtail motif relies on rational synthetic methods whereby a 1,9-bis(N-propylimino)dipyrromethane (bearing a bioconjugatable tether at the 5-position) is condensed with a dipyrromethane (bearing a protected 1,5-dihydroxypent-3-yl unit at the 5-position). The two hydroxy groups in the swallowtail motif of each of the resulting zinc porphyrins can be transformed to the corresponding diphosphate or diphosphonate product. A 4-(carboxymethyloxy)phenyl group provides the bioconjugatable tether. The six such porphyrins reported here are highly water-soluble (≥20 mM at room temperature in water at pH 7) as determined by visual inspection, UV–vis absorption spectroscopy, or 1H NMR spectroscopy. Covalent attachment was carried out in aqueous solution with the unprotected porphyrin diphosphonate and a monoclonal antibody against the T-cell receptor CD3ε. The resulting conjugate performed comparably to a commercially available fluorescein isothiocyanate-labeled antibody with Jurkat cells in flow cytometry and fluorescence microscopy assays. Taken together, this work enables preparation of useful quantities of water-soluble, bioconjugatable porphyrins in a compact architecture for applications in the life sciences. PMID:16704201

  10. Sequence-Based Classification Using Discriminatory Motif Feature Selection

    PubMed Central

    Xiong, Hao; Capurso, Daniel; Sen, Śaunak; Segal, Mark R.

    2011-01-01

    Most existing methods for sequence-based classification use exhaustive feature generation, employing, for example, all -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 , such that potentially important, longer () 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 available at http

  11. Identification of imine reductase-specific sequence motifs.

    PubMed

    Fademrecht, Silvia; Scheller, Philipp N; Nestl, Bettina M; Hauer, Bernhard; Pleiss, Jürgen

    2016-05-01

    Chiral amines are valuable building blocks for the production of a variety of pharmaceuticals, agrochemicals and other specialty chemicals. Only recently, imine reductases (IREDs) were discovered which catalyze the stereoselective reduction of imines to chiral amines. Although several IREDs were biochemically characterized in the last few years, knowledge of the reaction mechanism and the molecular basis of substrate specificity and stereoselectivity is limited. To gain further insights into the sequence-function relationships, the Imine Reductase Engineering Database (www.IRED.BioCatNet.de) was established and a systematic analysis of 530 putative IREDs was performed. A standard numbering scheme based on R-IRED-Sk was introduced to facilitate the identification and communication of structurally equivalent positions in different proteins. A conservation analysis revealed a highly conserved cofactor binding region and a predominantly hydrophobic substrate binding cleft. Two IRED-specific motifs were identified, the cofactor binding motif GLGxMGx5 [ATS]x4 Gx4 [VIL]WNR[TS]x2 [KR] and the active site motif Gx[DE]x[GDA]x[APS]x3 {K}x[ASL]x[LMVIAG]. Our results indicate a preference toward NADPH for all IREDs and explain why, despite their sequence similarity to β-hydroxyacid dehydrogenases (β-HADs), no conversion of β-hydroxyacids has been observed. Superfamily-specific conservations were investigated to explore the molecular basis of their stereopreference. Based on our analysis and previous experimental results on IRED mutants, an exclusive role of standard position 187 for stereoselectivity is excluded. Alternatively, two standard positions 139 and 194 were identified which are superfamily-specifically conserved and differ in R- and S-selective enzymes. Proteins 2016; 84:600-610. © 2016 Wiley Periodicals, Inc. PMID:26857686

  12. Functional angiocoupling between follicles and adjacent corpus luteum in heifers.

    PubMed

    Ginther, O J; Siddiqui, M A R; Baldrighi, J M

    2016-07-15

    In single ovulating cattle, ipsilateral versus contralateral interovarian relationships refer to a dominant follicle (DF) and CL in the same versus opposite ovaries. The ipsilateral relationship consists of the DF-CL and the devoid (no DF or CL) intraovarian pattern, and the contralateral relationship consists of the DF pattern and the CL pattern. The DF-CL pattern involves positive effects on both the DF and CL when adjacent (≤3-mm apart) versus separated as follows: greater diameter of DF (e.g., 10.5 ± 0.4 vs. 9.0 ± 0.4 mm), greater percentage of the DF wall with color Doppler signals of blood flow (40.2% ± 2.0% vs. 24.5% ± 1.9%), greater cross-sectional area of the CL (2.2 ± 0.1 vs. 1.8 ± 0.2 cm(2)), and greater percentage of the entire CL with blood flow signals (51.8% ± 1.2% vs. 42.5% ± 3.1%). Additional examples of positive coupling are (1) future DF on Day 0 (day of ovulation) is closer to the CL than the future largest subordinate and (2) diameter of growing follicles on Day 0 and the growth rate on Days 0 to 2 are greater for follicles that are adjacent than separated from the CL. An example of a negative intraovarian effect is decreasing diameter and loss of future DF status of a largest follicle when adjacent to a regressing CL. The impact of the continuity of ovarian angioarchitecture during the periovulatory follicular wave was exemplified in 17 of 18 waves by conversion of an ovary with only the preovulatory follicle to the postovulatory DF-CL pattern. Functional angiocoupling from commonality in angioarchitecture of the DF and adjacent CL would account for both the positive two-way coupling between DF and CL during the luteal phase and the negative effect of a regressing CL on an adjacent follicle during luteolysis. PMID:27056414

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

    PubMed

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

    2016-09-01

    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. PMID:26939549

  14. Topological defect motifs in two-dimensional Coulomb clusters.

    PubMed

    Radzvilavičius, A; Anisimovas, E

    2011-09-28

    We study the distribution of topological defects in two-dimensional Coulomb clusters with parabolic lateral confinement. The minima hopping algorithm based on molecular dynamics is used to efficiently locate the ground- and low-energy metastable states, and their structure is analysed by means of the Delaunay triangulation. The size, structure and distribution of geometry-induced lattice imperfections strongly depends on the system size and the energetic state. Besides isolated disclinations and dislocations, classification of defect motifs includes defect compounds-grain boundaries, rosette defects, vacancies and interstitial particles. Proliferation of defects in metastable configurations destroys the orientational order of the Wigner lattice. PMID:21891854

  15. Genome wide identification of regulatory motifs in Bacillus subtilis

    PubMed Central

    Mwangi, Michael M; Siggia, Eric D

    2003-01-01

    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 our algorithm allows for the

  16. Do short, frequent DNA sequence motifs mould the epigenome?

    PubMed

    Quante, Timo; Bird, Adrian

    2016-04-01

    'Epigenome' refers to the panoply of chemical modifications borne by DNA and its associated proteins that locally affect genome function. Epigenomic patterns are thought to be determined by external constraints resulting from development, disease and the environment, but DNA sequence is also a potential influence. We propose that domains of relatively uniform DNA base composition may modulate the epigenome through cell type-specific proteins that recognize short, frequent sequence motifs. Differential recruitment of epigenomic modifiers may adjust gene expression in multigene blocks as an alternative to tuning the activity of each gene separately, thus simplifying gene expression programming. PMID:26837845

  17. Fast and Accurate Discovery of Degenerate Linear Motifs in Protein Sequences

    PubMed Central

    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

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

    PubMed Central

    2013-01-01

    Background 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. Results 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. Conclusions Our novel heuristic algorithm, TFBSGroup, is able to quickly identify nearly exact matches for long

  19. Discovery and optimization of a novel series of highly CNS penetrant M4 PAMs based on a 5,6-dimethyl-4-(piperidin-1-yl)thieno[2,3-d]pyrimidine core.

    PubMed

    Wood, Michael R; Noetzel, Meredith J; Engers, Julie L; Bollinger, Katrina A; Melancon, Bruce J; Tarr, James C; Han, Changho; West, Mary; Gregro, Alison R; Lamsal, Atin; Chang, Sichen; Ajmera, Sonia; Smith, Emery; Chase, Peter; Hodder, Peter S; Bubser, Michael; Jones, Carrie K; Hopkins, Corey R; Emmitte, Kyle A; Niswender, Colleen M; Wood, Michael W; Duggan, Mark E; Conn, P Jeffrey; Bridges, Thomas M; Lindsley, Craig W

    2016-07-01

    This Letter describes the chemical optimization of a novel series of M4 positive allosteric modulators (PAMs) based on a 5,6-dimethyl-4-(piperidin-1-yl)thieno[2,3-d]pyrimidine core, identified from an MLPCN functional high-throughput screen. The HTS hit was potent and selective, but not CNS penetrant. Potency was maintained, while CNS penetration was improved (rat brain:plasma Kp=0.74), within the original core after several rounds of optimization; however, the thieno[2,3-d]pyrimidine core was subject to extensive oxidative metabolism. Ultimately, we identified a 6-fluoroquinazoline core replacement that afforded good M4 PAM potency, muscarinic receptor subtype selectivity and CNS penetration (rat brain:plasma Kp>10). Moreover, this campaign provided fundamentally distinct M4 PAM chemotypes, greatly expanding the available structural diversity for this exciting CNS target. PMID:27185330

  20. Discovery of GluN2A-Selective NMDA Receptor Positive Allosteric Modulators (PAMs): Tuning Deactivation Kinetics via Structure-Based Design.

    PubMed

    Volgraf, Matthew; Sellers, Benjamin D; Jiang, Yu; Wu, Guosheng; Ly, Cuong Q; Villemure, Elisia; Pastor, Richard M; Yuen, Po-wai; Lu, Aijun; Luo, Xifeng; Liu, Mingcui; Zhang, Shun; Sun, Liang; Fu, Yuhong; Lupardus, Patrick J; Wallweber, Heidi J A; Liederer, Bianca M; Deshmukh, Gauri; Plise, Emile; Tay, Suzanne; Reynen, Paul; Herrington, James; Gustafson, Amy; Liu, Yichin; Dirksen, Akim; Dietz, Matthias G A; Liu, Yanzhou; Wang, Tzu-Ming; Hanson, Jesse E; Hackos, David; Scearce-Levie, Kimberly; Schwarz, Jacob B

    2016-03-24

    The N-methyl-D-aspartate receptor (NMDAR) is a Na(+) and Ca(2+) permeable ionotropic glutamate receptor that is activated by the coagonists glycine and glutamate. NMDARs are critical to synaptic signaling and plasticity, and their dysfunction has been implicated in a number of neurological disorders, including schizophrenia, depression, and Alzheimer's disease. Herein we describe the discovery of potent GluN2A-selective NMDAR positive allosteric modulators (PAMs) starting from a high-throughput screening hit. Using structure-based design, we sought to increase potency at the GluN2A subtype, while improving selectivity against related α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). The structure-activity relationship of channel deactivation kinetics was studied using a combination of electrophysiology and protein crystallography. Effective incorporation of these strategies resulted in the discovery of GNE-0723 (46), a highly potent and brain penetrant GluN2A-selective NMDAR PAM suitable for in vivo characterization. PMID:26919761

  1. Automated protein motif generation in the structure-based protein function prediction tool ProMOL.

    PubMed

    Osipovitch, Mikhail; Lambrecht, Mitchell; Baker, Cameron; Madha, Shariq; Mills, Jeffrey L; Craig, Paul A; Bernstein, Herbert J

    2015-12-01

    ProMOL, a plugin for the PyMOL molecular graphics system, is a structure-based protein function prediction tool. ProMOL includes a set of routines for building motif templates that are used for screening query structures for enzyme active sites. Previously, each motif template was generated manually and required supervision in the optimization of parameters for sensitivity and selectivity. We developed an algorithm and workflow for the automation of motif building and testing routines in ProMOL. The algorithm uses a set of empirically derived parameters for optimization and requires little user intervention. The automated motif generation algorithm was first tested in a performance comparison with a set of manually generated motifs based on identical active sites from the same 112 PDB entries. The two sets of motifs were equally effective in identifying alignments with homologs and in rejecting alignments with unrelated structures. A second set of 296 active site motifs were generated automatically, based on Catalytic Site Atlas entries with literature citations, as an expansion of the library of existing manually generated motif templates. The new motif templates exhibited comparable performance to the existing ones in terms of hit rates against native structures, homologs with the same EC and Pfam designations, and randomly selected unrelated structures with a different EC designation at the first EC digit, as well as in terms of RMSD values obtained from local structural alignments of motifs and query structures. This research is supported by NIH grant GM078077. PMID:26573864

  2. Systematic discovery and characterization of regulatory motifs in ENCODE TF binding experiments

    PubMed Central

    Kheradpour, Pouya; Kellis, Manolis

    2014-01-01

    Recent advances in technology have led to a dramatic increase in the number of available transcription factor ChIP-seq and ChIP-chip data sets. Understanding the motif content of these data sets is an important step in understanding the underlying mechanisms of regulation. Here we provide a systematic motif analysis for 427 human ChIP-seq data sets using motifs curated from the literature and also discovered de novo using five established motif discovery tools. We use a systematic pipeline for calculating motif enrichment in each data set, providing a principled way for choosing between motif variants found in the literature and for flagging potentially problematic data sets. Our analysis confirms the known specificity of 41 of the 56 analyzed factor groups and reveals motifs of potential cofactors. We also use cell type-specific binding to find factors active in specific conditions. The resource we provide is accessible both for browsing a small number of factors and for performing large-scale systematic analyses. We provide motif matrices, instances and enrichments in each of the ENCODE data sets. The motifs discovered here have been used in parallel studies to validate the specificity of antibodies, understand cooperativity between data sets and measure the variation of motif binding across individuals and species. PMID:24335146

  3. Two ribosomal DNA-binding factors interact with a cluster of motifs on the 5' external transcribed spacer, upstream from the primary pre-rRNA processing site in a higher plant.

    PubMed

    Caparros-Ruiz, D; Lahmy, S; Piersanti, S; Echeverría, M

    1997-08-01

    In radish the primary processing site in pre-rRNA has been mapped to a TTTTCGCGC sequence (motif P) in the 5' external transcribed spacer (5' ETS) of the ribosomal DNA (rDNA) [Delcasso-Tremousaygue, D., Grellet, F., Panabières, F., Ananiev, E. & Delseny, M. (1988) Eur. J. Biochem. 172, 767-776]. The processing site is just downstream of four similar motifs named A1, A2, A3 and B. The five motifs constitute cluster A123BP. We have described previously that in radish extracts a nuclear protein, nuclear factor B (NF B) specifically binds to motif B [Echeverría, M., Penon, P. & Delseny, M. (1994) Mol. Gen. Genet. 243, 442-452]. Here, by means of electrophoretic-mobility-shift assays, we describe an rDNA-binding activity, nuclear factor D (NF D), that interacts with the A123BP cluster. Using various rDNA probes and competitors we show that NF D binds specifically to the A123 clustered motifs but not to similar B or P motifs. We used sequence-specific DNA-affinity chromatography to separate NF D from NF B. DNase I footprinting was used to map the binding site of NF D on the A123BP cluster and we compared it with that of NF B on the same probe. The footprint of NF D extends from the A1 motif to the 5' end of the NF B-binding site and includes motifs A2 and A3 on each strand. The footprinting of NF B is restricted to motif B and adjacent nucleotides. Thus the NF D-binding and NF B-binding sites are distinct but overlap. These two factors bind with a high specificity to the A123BP cluster in the radish 5' ETS. The possibility that these factors regulate rDNA transcription elongation at the level of the primary pre-rRNA processing site in crucifers is discussed. PMID:9288923

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

    PubMed

    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. PMID:24667216

  5. Proline rich motifs as drug targets in immune mediated disorders.

    PubMed

    Srinivasan, Mythily; Dunker, A Keith

    2012-01-01

    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. PMID:22666276

  6. Phosphotyrosine Substrate Sequence Motifs for Dual Specificity Phosphatases

    PubMed Central

    Zhao, Bryan M.; Keasey, Sarah L.; Tropea, Joseph E.; Lountos, George T.; Dyas, Beverly K.; Cherry, Scott; Raran-Kurussi, Sreejith; Waugh, David S.; Ulrich, Robert G.

    2015-01-01

    Protein tyrosine phosphatases dephosphorylate tyrosine residues of proteins, whereas, dual specificity phosphatases (DUSPs) are a subgroup of protein tyrosine phosphatases that dephosphorylate not only Tyr(P) residue, but also the Ser(P) and Thr(P) residues of proteins. The DUSPs are linked to the regulation of many cellular functions and signaling pathways. Though many cellular targets of DUSPs are known, the relationship between catalytic activity and substrate specificity is poorly defined. We investigated the interactions of peptide substrates with select DUSPs of four types: MAP kinases (DUSP1 and DUSP7), atypical (DUSP3, DUSP14, DUSP22 and DUSP27), viral (variola VH1), and Cdc25 (A-C). Phosphatase recognition sites were experimentally determined by measuring dephosphorylation of 6,218 microarrayed Tyr(P) peptides representing confirmed and theoretical phosphorylation motifs from the cellular proteome. A broad continuum of dephosphorylation was observed across the microarrayed peptide substrates for all phosphatases, suggesting a complex relationship between substrate sequence recognition and optimal activity. Further analysis of peptide dephosphorylation by hierarchical clustering indicated that DUSPs could be organized by substrate sequence motifs, and peptide-specificities by phylogenetic relationships among the catalytic domains. The most highly dephosphorylated peptides represented proteins from 29 cell-signaling pathways, greatly expanding the list of potential targets of DUSPs. These newly identified DUSP substrates will be important for examining structure-activity relationships with physiologically relevant targets. PMID:26302245

  7. A motif for reversible nitric oxide interactions in metalloenzymes.

    PubMed

    Zhang, Shiyu; Melzer, Marie M; Sen, S Nermin; Çelebi-Ölçüm, Nihan; Warren, Timothy H

    2016-07-01

    Nitric oxide (NO) participates in numerous biological processes, such as signalling in the respiratory system and vasodilation in the cardiovascular system. Many metal-mediated processes involve direct reaction of NO to form a metal-nitrosyl (M-NO), as occurs at the Fe(2+) centres of soluble guanylate cyclase or cytochrome c oxidase. However, some copper electron-transfer proteins that bear a type 1 Cu site (His2Cu-Cys) reversibly bind NO by an unknown motif. Here, we use model complexes of type 1 Cu sites based on tris(pyrazolyl)borate copper thiolates [Cu(II)]-SR to unravel the factors involved in NO reactivity. Addition of NO provides the fully characterized S-nitrosothiol adduct [Cu(I)](κ(1)-N(O)SR), which reversibly loses NO on purging with an inert gas. Computational analysis outlines a low-barrier pathway for the capture and release of NO. These findings suggest a new motif for reversible binding of NO at bioinorganic metal centres that can interconvert NO and RSNO molecular signals at copper sites. PMID:27325092

  8. Ultrasensitive response motifs: basic amplifiers in molecular signalling networks

    PubMed Central

    Zhang, Qiang; Bhattacharya, Sudin; Andersen, Melvin E.

    2013-01-01

    Multi-component signal transduction pathways and gene regulatory circuits underpin integrated cellular responses to perturbations. A recurring set of network motifs serve as the basic building blocks of these molecular signalling networks. This review focuses on ultrasensitive response motifs (URMs) that amplify small percentage changes in the input signal into larger percentage changes in the output response. URMs generally possess a sigmoid input–output relationship that is steeper than the Michaelis–Menten type of response and is often approximated by the Hill function. Six types of URMs can be commonly found in intracellular molecular networks and each has a distinct kinetic mechanism for signal amplification. These URMs are: (i) positive cooperative binding, (ii) homo-multimerization, (iii) multistep signalling, (iv) molecular titration, (v) zero-order covalent modification cycle and (vi) positive feedback. Multiple URMs can be combined to generate highly switch-like responses. Serving as basic signal amplifiers, these URMs are essential for molecular circuits to produce complex nonlinear dynamics, including multistability, robust adaptation and oscillation. These dynamic properties are in turn responsible for higher-level cellular behaviours, such as cell fate determination, homeostasis and biological rhythm. PMID:23615029

  9. Evolutionary optimization of transcription factor binding motif detection.

    PubMed

    Zhang, Zhao; Wang, Ze; Mai, Guoqin; Luo, Youxi; Zhao, Miaomiao; Zhou, Fengfeng

    2015-01-01

    All the cell types are under strict control of how their genes are transcribed into expressed transcripts by the temporally dynamic orchestration of the transcription factor binding activities. Given a set of known binding sites (BSs) of a given transcription factor (TF), computational TFBS screening technique represents a cost efficient and large scale strategy to complement the experimental ones. There are two major classes of computational TFBS prediction algorithms based on the tertiary and primary structures, respectively. A tertiary structure based algorithm tries to calculate the binding affinity between a query DNA fragment and the tertiary structure of the given TF. Due to the limited number of available TF tertiary structures, primary structure based TFBS prediction algorithm is a necessary complementary technique for large scale TFBS screening. This study proposes a novel evolutionary algorithm to randomly mutate the weights of different positions in the binding motif of a TF, so that the overall TFBS prediction accuracy is optimized. The comparison with the most widely used algorithm, Position Weight Matrix (PWM), suggests that our algorithm performs better or the same level in all the performance measurements, including sensitivity, specificity, accuracy and Matthews correlation coefficient. Our data also suggests that it is necessary to remove the widely used assumption of independence between motif positions. The supplementary material may be found at: http://www.healthinformaticslab.org/supp/ . PMID:25387969

  10. Applying Side-chain Flexibility in Motifs for Protein Docking

    PubMed Central

    Liu, Hui; Lin, Feng; Yang, Jian-Li; Wang, Hong-Rui; Liu, Xiu-Ling

    2015-01-01

    Conventional rigid docking algorithms have been unsatisfactory in their computational results, largely due to the fact that protein structures are flexible in live environments. In response, we propose to introduce the side-chain flexibility in protein motif into the docking. First, the Morse theory is applied to curvature labeling and surface region growing, for segmentation of the protein surface into smaller patches. Then, the protein is described by an ensemble of conformations that incorporate the flexibility of interface side chains and are sampled using rotamers. Next, a 3D rotation invariant shape descriptor is proposed to deal with the flexible motifs and surface patches; thus, pairwise complementarity matching is needed only between the convex patches of ligand and the concave patches of receptor. The iterative closest point (ICP) algorithm is implemented for geometric alignment of the two 3D protein surface patches. Compared with the fast Fourier transform-based global geometric matching algorithm and other methods, our FlexDock system generates much less false-positive docking results, which benefits identification of the complementary candidates. Our computational experiments show the advantages of the proposed flexible docking algorithm over its counterparts. PMID:26508871

  11. Applying Side-chain Flexibility in Motifs for Protein Docking.

    PubMed

    Liu, Hui; Lin, Feng; Yang, Jian-Li; Wang, Hong-Rui; Liu, Xiu-Ling

    2015-01-01

    Conventional rigid docking algorithms have been unsatisfactory in their computational results, largely due to the fact that protein structures are flexible in live environments. In response, we propose to introduce the side-chain flexibility in protein motif into the docking. First, the Morse theory is applied to curvature labeling and surface region growing, for segmentation of the protein surface into smaller patches. Then, the protein is described by an ensemble of conformations that incorporate the flexibility of interface side chains and are sampled using rotamers. Next, a 3D rotation invariant shape descriptor is proposed to deal with the flexible motifs and surface patches; thus, pairwise complementarity matching is needed only between the convex patches of ligand and the concave patches of receptor. The iterative closest point (ICP) algorithm is implemented for geometric alignment of the two 3D protein surface patches. Compared with the fast Fourier transform-based global geometric matching algorithm and other methods, our FlexDock system generates much less false-positive docking results, which benefits identification of the complementary candidates. Our computational experiments show the advantages of the proposed flexible docking algorithm over its counterparts. PMID:26508871

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

    PubMed Central

    Srinivasan, Mythily; Dunker, A. Keith

    2012-01-01

    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. PMID:22666276

  13. Computing distribution of scale independent motifs in biological sequences

    PubMed Central

    Almeida, Jonas S; Vinga, Susana

    2006-01-01

    The use of Chaos Game Representation (CGR) or its generalization, Universal Sequence Maps (USM), to describe the distribution of biological sequences has been found objectionable because of the fractal structure of that coordinate system. Consequently, the investigation of distribution of symbolic motifs at multiple scales is hampered by an inexact association between distance and sequence dissimilarity. A solution to this problem could unleash the use of iterative maps as phase-state representation of sequences where its statistical properties can be conveniently investigated. In this study a family of kernel density functions is described that accommodates the fractal nature of iterative function representations of symbolic sequences and, consequently, enables the exact investigation of sequence motifs of arbitrary lengths in that scale-independent representation. Furthermore, the proposed kernel density includes both Markovian succession and currently used alignment-free sequence dissimilarity metrics as special solutions. Therefore, the fractal kernel described is in fact a generalization that provides a common framework for a diverse suite of sequence analysis techniques. PMID:17049089

  14. Impact of adjacent land use on coastal wetland sediments.

    PubMed

    Karstens, Svenja; Buczko, Uwe; Jurasinski, Gerald; Peticzka, Robert; Glatzel, Stephan

    2016-04-15

    Coastal wetlands link terrestrial with marine ecosystems and are influenced from both land and sea. Therefore, they are ecotones with strong biogeochemical gradients. We analyzed sediment characteristics including macronutrients (C, N, P, K, Mg, Ca, S) and heavy metals (Mn, Fe, Cu, Zn, Al, Co, Cr, Ni) of two coastal wetlands dominated by Phragmites australis at the Darss-Zingst Bodden Chain, a lagoon system at the Southern Baltic Sea, to identify the impact of adjacent land use and to distinguish between influences from land or sea. In the wetland directly adjacent to cropland (study site Dabitz) heavy metal concentrations were significantly elevated. Fertilizer application led to heavy metal accumulation in the sediments of the adjacent wetland zones. In contrast, at the other study site (Michaelsdorf), where the hinterland has been used as pasture, heavy metal concentrations were low. While the amount of macronutrients was also influenced by vegetation characteristics (e.g. carbon) or water chemistry (e.g. sulfate), the accumulation of heavy metals is regarded as purely anthropogenic influence. A principal component analysis (PCA) based on the sediment data showed that the wetland fringes of the two study sites are not distinguishable, neither in their macronutrient status nor in their concentrations of heavy metals, whereas the interior zones exhibit large differences in terms of heavy metal concentrations. This suggests that seaside influences are minor compared to influences from land. Altogether, heavy metal concentrations were still below national precautionary and action values. However, if we regard the macronutrient and heavy metal concentrations in the wetland fringes as the natural background values, an accumulation of trace elements from agricultural production in the hinterland is apparent. Thus, coastal wetlands bordering croplands may function as effective pollutant buffers today, but the future development has to be monitored closely to avoid

  15. Over-represented localized sequence motifs in ribosomal protein gene promoters of basal metazoans.

    PubMed

    Perina, Drago; Korolija, Marina; Roller, Maša; Harcet, Matija; Jeličić, Branka; Mikoč, Andreja; Cetković, Helena

    2011-07-01

    Equimolecular presence of ribosomal proteins (RPs) in the cell is needed for ribosome assembly and is achieved by synchronized expression of ribosomal protein genes (RPGs) with promoters of similar strengths. Over-represented motifs of RPG promoter regions are identified as targets for specific transcription factors. Unlike RPs, those motifs are not conserved between mammals, drosophila, and yeast. We analyzed RPGs proximal promoter regions of three basal metazoans with sequenced genomes: sponge, cnidarian, and placozoan and found common features, such as 5'-terminal oligopyrimidine tracts and TATA-boxes. Furthermore, we identified over-represented motifs, some of which displayed the highest similarity to motifs abundant in human RPG promoters and not present in Drosophila or yeast. Our results indicate that humans over-represented motifs, as well as corresponding domains of transcription factors, were established very early in metazoan evolution. The fast evolving nature of RPGs regulatory network leads to formation of other, lineage specific, over-represented motifs. PMID:21457775

  16. Hydrogen-bond motifs in the crystals of hydrophobic amino acids.

    PubMed

    Fábián, László; Chisholm, James A; Galek, Peter T A; Motherwell, W D Samuel; Feeder, Neil

    2008-08-01

    A computer program has been developed to survey a set of crystal structures for hydrogen-bond motifs. Possible ring and chain motifs are generated automatically from a user-defined list of interacting molecular fragments and intermolecular interactions. The new program was used to analyse the hydrogen-bond networks in the crystals of 52 zwitterionic alpha-amino acids. All the possible chain motifs (repeating 1-4 molecules) are frequent, while the frequency of ring motifs (2-6 molecules) ranges from 0 to 85% of the structures. The list of motifs displayed by each structure reveals structural similarities and it can be used to compare polymorphs. The motifs formed in cocrystals of alpha-amino acids and in crystals of beta- and gamma-amino acids are similar to those of alpha-amino acids. PMID:18641453

  17. Exophytic Atheroma Mimicking Papillary Fibroelastoma Adjacent to the Aortic Valve.

    PubMed

    Cho, Tomoki; Tokunaga, Shigehiko; Yasuda, Shota; Izubuchi, Ryo; Masuda, Munetaka

    2015-09-01

    Follow-up echocardiography in a 69-year-old man with alcoholic cardiomyopathy showed a mass above the aortic valve near the left coronary ostium. Transesophageal echocardiography and computed tomography suggested a papillary fibroelastoma with a high risk of embolism. At operation we found an exophytic atheroma adjacent to the left coronary artery orifice. The atheroma was removed, and the patient made an uneventful recovery. We describe this very rare case of an exophytic atheroma mimicking a papillary fibroelastoma situated at the left coronary orifice. PMID:26354633

  18. Compression of adjacent anatomical structures by pulmonary artery dilation.

    PubMed

    Dakkak, Wael; Tonelli, Adriano R

    2016-06-01

    Pulmonary hypertension is the commonest condition leading to dilated pulmonary artery. We describe three different types of compression of adjacent anatomical structures by dilated pulmonary arteries. We included involvement of the left main coronary artery, left recurrent laryngeal nerve and tracheobronchial tree. Compression of these structures can cause major complications such as myocardial ischemia, hoarseness and major airway stenosis. We present a case for each scenario and review the literature for each of these complications, focusing on patients' characteristics and contemporary management. PMID:26898826

  19. Synthesis of a Molecule with Four Different Adjacent Pnictogens.

    PubMed

    Hinz, Alexander; Schulz, Axel; Villinger, Alexander

    2016-08-22

    The synthesis of a molecule containing four adjacent different pnictogens was attempted by conversion of a Group 15 allyl analogue anion [Mes*NAsPMes*](-) (Mes*=2,4,6-tri-tert-butylphenyl) with antimony(III) chloride. A suitable precursor is Mes*N(H)AsPMes* (1) for which several syntheses were investigated. The anions afforded by deprotonation of Mes*N(H)AsPMes* were found to be labile and, therefore, salts could not be isolated. However, the in situ generated anions could be quenched with SbCl3 , yielding Mes*N(SbCl2 )AsPMes* (4). PMID:27377437

  20. Stereoselective Organocatalytic Synthesis of Oxindoles with Adjacent Tetrasubstituted Stereocenters.

    PubMed

    Engl, Oliver D; Fritz, Sven P; Wennemers, Helma

    2015-07-01

    Oxindoles with adjacent tetrasubstituted stereocenters were obtained in high yields and stereoselectivities by organocatalyzed conjugate addition reactions of monothiomalonates (MTMs) to isatin-derived N-Cbz ketimines. The method requires only a low catalyst loading (2 mol %) and proceeds under mild reaction conditions. Both enantiomers are accessible in good yields and excellent stereoselectivities by using either Takemoto's catalyst or a cinchona alkaloid derivative. The synthetic methodology allowed establishment of a straightforward route to derivatives of the gastrin/cholecystokinin-B receptor antagonist AG-041R. PMID:26033441