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Sample records for hammerhead ribozyme complex

  1. Eukaryotic Penelope-Like Retroelements Encode Hammerhead Ribozyme Motifs

    Science.gov (United States)

    Cervera, Amelia; De la Peña, Marcos

    2014-01-01

    Small self-cleaving RNAs, such as the paradigmatic Hammerhead ribozyme (HHR), have been recently found widespread in DNA genomes across all kingdoms of life. In this work, we found that new HHR variants are preserved in the ancient family of Penelope-like elements (PLEs), a group of eukaryotic retrotransposons regarded as exceptional for encoding telomerase-like retrotranscriptases and spliceosomal introns. Our bioinformatic analysis revealed not only the presence of minimalist HHRs in the two flanking repeats of PLEs but also their massive and widespread occurrence in metazoan genomes. The architecture of these ribozymes indicates that they may work as dimers, although their low self-cleavage activity in vitro suggests the requirement of other factors in vivo. In plants, however, PLEs show canonical HHRs, whereas fungi and protist PLEs encode ribozyme variants with a stable active conformation as monomers. Overall, our data confirm the connection of self-cleaving RNAs with eukaryotic retroelements and unveil these motifs as a significant fraction of the encoded information in eukaryotic genomes. PMID:25135949

  2. LNA nucleotides improve cleavage efficiency of singular and binary hammerhead ribozymes

    DEFF Research Database (Denmark)

    Christiansen, Janne K; Lobedanz, Sune; Arar, Khalil

    2007-01-01

    Variants of trans-acting hammerhead ribozymes were modified with Locked Nucleic Acid (LNA) nucleotides to reduce their size, to improve access to their RNA target and to explore combinational properties of binary constructs. Using low Mg(2+) concentrations and low substrate and ribozyme concentra......Variants of trans-acting hammerhead ribozymes were modified with Locked Nucleic Acid (LNA) nucleotides to reduce their size, to improve access to their RNA target and to explore combinational properties of binary constructs. Using low Mg(2+) concentrations and low substrate and ribozyme...... molecules with each half binding to the substrate. Efficient, binary hammerhead ribozymes were pursued in a combinatorial approach using a 6-times 5 library, which was analysed concerning the best combinations, buffer conditions and fragment ratios....

  3. Experimental cancer gene therapy by multiple anti-survivin hammerhead ribozymes.

    Science.gov (United States)

    Fei, Qi; Zhang, Hongyu; Fu, Lili; Dai, Xinlan; Gao, Baomei; Ni, Min; Ge, Chao; Li, Jinjun; Ding, Xia; Ke, Yuwen; Yao, Xuebiao; Zhu, Jingde

    2008-06-01

    To improve the efficacy of gene therapy for cancer, we designed four hammerhead ribozyme adenoviruses (R1 to R4) targeting the exposed regions of survivin mRNA. In addition to the in vitro characterization, which included a determination of the sequence specificity of cleavage by primer extension, assays for cell proliferation and for in vivo tumor growth were used to score for ribozyme efficiency. The resulting suppression of survivin expression induced mitotic catastrophe and cell death via the caspase-3-dependent pathway. Importantly, administration of the ribozyme adenoviruses inhibited tumor growth in a hepatocellular carcinoma xenograft mouse model. Co-expression of R1, R3 and R4 ribozymes synergistically suppressed survivin and, as this combination targets all major forms of the survivin transcripts, produced the most potent anti-cancer effects. The adenoviruses carrying the multiple hammerhead ribozymes described in this report offered a robust gene therapy strategy against cancer.

  4. Peripheral regions of natural hammerhead ribozymes greatly increase their self-cleavage activity

    Science.gov (United States)

    De la Peña, Marcos; Gago, Selma; Flores, Ricardo

    2003-01-01

    Natural hammerhead ribozymes are mostly found in some viroid and viroid-like RNAs and catalyze their cis cleavage during replication. Hammerheads have been manipulated to act in trans and assumed to have a similar catalytic behavior in this artificial context. However, we show here that two natural cis-acting hammerheads self-cleave much faster than trans-acting derivatives and other reported artificial hammerheads. Moreover, modifications of the peripheral loops 1 and 2 of one of these natural hammerheads induced a >100-fold reduction of the self-cleavage constant, whereas engineering a trans-acting artificial hammerhead into a cis derivative by introducing a loop 1 had no effect. These data show that regions external to the central conserved core of natural hammerheads play a role in catalysis, and suggest the existence of tertiary interactions between these peripheral regions. The interactions, determined by the sequence and size of loops 1 and 2 and most likely of helices I and II, must result from natural selection and should be studied in order to better understand the hammerhead requirements in vivo. PMID:14532128

  5. Numerous small hammerhead ribozyme variants associated with Penelope-like retrotransposons cleave RNA as dimers.

    Science.gov (United States)

    Lünse, Christina E; Weinberg, Zasha; Breaker, Ronald R

    2016-11-18

    Hammerhead ribozymes represent the most common of the nine natural classes of self-cleaving RNAs. The hammerhead catalytic core includes 11 highly-conserved nucleotides located largely within the unpaired regions of a junction formed by stems I, II and III. The vast majority of previously reported examples carry an additional pseudoknot or other tertiary interactions between nucleotides that precede stem I and nucleotides in the loop of stem II. These extra contacts are critical for high-speed RNA catalysis. Herein, we report the discovery of ∼150,000 additional variant hammerhead representatives that exhibit diminished stem III substructures. These variants are frequently associated with Penelope-like retrotransposons, which are a type of mobile genetic element. Kinetic analyses indicate that these RNAs form dimers to cleave RNA.

  6. Phylogenetic footprinting of non-coding RNA: hammerhead ribozyme sequences in a satellite DNA family of Dolichopoda cave crickets (Orthoptera, Rhaphidophoridae).

    Science.gov (United States)

    Martinsen, Lene; Johnsen, Arild; Venanzetti, Federica; Bachmann, Lutz

    2010-01-04

    The great variety in sequence, length, complexity, and abundance of satellite DNA has made it difficult to ascribe any function to this genome component. Recent studies have shown that satellite DNA can be transcribed and be involved in regulation of chromatin structure and gene expression. Some satellite DNAs, such as the pDo500 sequence family in Dolichopoda cave crickets, have a catalytic hammerhead (HH) ribozyme structure and activity embedded within each repeat. We assessed the phylogenetic footprints of the HH ribozyme within the pDo500 sequences from 38 different populations representing 12 species of Dolichopoda. The HH region was significantly more conserved than the non-hammerhead (NHH) region of the pDo500 repeat. In addition, stems were more conserved than loops. In stems, several compensatory mutations were detected that maintain base pairing. The core region of the HH ribozyme was affected by very few nucleotide substitutions and the cleavage position was altered only once among 198 sequences. RNA folding of the HH sequences revealed that a potentially active HH ribozyme can be found in most of the Dolichopoda populations and species. The phylogenetic footprints suggest that the HH region of the pDo500 sequence family is selected for function in Dolichopoda cave crickets. However, the functional role of HH ribozymes in eukaryotic organisms is unclear. The possible functions have been related to trans cleavage of an RNA target by a ribonucleoprotein and regulation of gene expression. Whether the HH ribozyme in Dolichopoda is involved in similar functions remains to be investigated. Future studies need to demonstrate how the observed nucleotide changes and evolutionary constraint have affected the catalytic efficiency of the hammerhead.

  7. Phylogenetic footprinting of non-coding RNA: hammerhead ribozyme sequences in a satellite DNA family of Dolichopoda cave crickets (Orthoptera, Rhaphidophoridae

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    Venanzetti Federica

    2010-01-01

    Full Text Available Abstract Background The great variety in sequence, length, complexity, and abundance of satellite DNA has made it difficult to ascribe any function to this genome component. Recent studies have shown that satellite DNA can be transcribed and be involved in regulation of chromatin structure and gene expression. Some satellite DNAs, such as the pDo500 sequence family in Dolichopoda cave crickets, have a catalytic hammerhead (HH ribozyme structure and activity embedded within each repeat. Results We assessed the phylogenetic footprints of the HH ribozyme within the pDo500 sequences from 38 different populations representing 12 species of Dolichopoda. The HH region was significantly more conserved than the non-hammerhead (NHH region of the pDo500 repeat. In addition, stems were more conserved than loops. In stems, several compensatory mutations were detected that maintain base pairing. The core region of the HH ribozyme was affected by very few nucleotide substitutions and the cleavage position was altered only once among 198 sequences. RNA folding of the HH sequences revealed that a potentially active HH ribozyme can be found in most of the Dolichopoda populations and species. Conclusions The phylogenetic footprints suggest that the HH region of the pDo500 sequence family is selected for function in Dolichopoda cave crickets. However, the functional role of HH ribozymes in eukaryotic organisms is unclear. The possible functions have been related to trans cleavage of an RNA target by a ribonucleoprotein and regulation of gene expression. Whether the HH ribozyme in Dolichopoda is involved in similar functions remains to be investigated. Future studies need to demonstrate how the observed nucleotide changes and evolutionary constraint have affected the catalytic efficiency of the hammerhead.

  8. Effective suppression of Dengue fever virus in mosquito cell cultures using retroviral transduction of hammerhead ribozymes targeting the viral genome

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    Mohammed Ahmed

    2009-06-01

    Full Text Available Abstract Outbreaks of Dengue impose a heavy economic burden on developing countries in terms of vector control and human morbidity. Effective vaccines against all four serotypes of Dengue are in development, but population replacement with transgenic vectors unable to transmit the virus might ultimately prove to be an effective approach to disease suppression, or even eradication. A key element of the refractory transgenic vector approach is the development of transgenes that effectively prohibit viral transmission. In this report we test the effectiveness of several hammerhead ribozymes for suppressing DENV in lentivirus-transduced mosquito cells in an attempt to mimic the transgenic use of these effector molecules in mosquitoes. A lentivirus vector that expresses these ribozymes as a fusion RNA molecule using an Ae. aegypti tRNAval promoter and terminating with a 60A tail insures optimal expression, localization, and activity of the hammerhead ribozyme against the DENV genome. Among the 14 hammerhead ribozymes we designed to attack the DENV-2 NGC genome, several appear to be relatively effective in reducing virus production from transduced cells by as much as 2 logs. Among the sequences targeted are 10 that are conserved among all DENV serotype 2 strains. Our results confirm that hammerhead ribozymes can be effective in suppressing DENV in a transgenic approach, and provide an alternative or supplementary approach to proposed siRNA strategies for DENV suppression in transgenic mosquitoes.

  9. Low-magnesium, trans-cleavage activity by type III, tertiary stabilized hammerhead ribozymes with stem 1 discontinuities

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    Burke Donald H

    2005-08-01

    Full Text Available Abstract Background Low concentrations of free magnesium in the intracellular environment can present critical limitations for hammerhead ribozymes, especially for those that are designed for intermolecular (trans cleavage of a host or pathogen RNA. Tertiary stabilizing motifs (TSM's from natural and artificial ribozymes with a "type I" topology have been exploited to stabilize trans-cleaving hammerheads. Ribozymes with "type II" or "type III" topologies might seem incompatible with conversion to trans-cleavage designs, because opening the loop at the end of stem 1 or stem 2 to accommodate substrate binding is expected to disrupt the TSM and eliminate tertiary stabilization. Results Stem 1, together with single-stranded segments capping or internal to this stem, contains both the substrate-binding and tertiary stabilization functions. This stem was made discontinuous within the sTRSV hammerhead ribozyme, thereby separating the two functions into discrete structural segments. The resulting ribozyme, designated "RzC," cleaved its 13 nucleotide target substrate at MgCl2 concentrations as low as 0.2 mM at 25°C and 0.5 mM at 37°C. Under multiple-turnover conditions, nearly thirty turnovers were observed at the highest substrate:RzC ribozyme ratios. Similar stabilization was observed for several derivatives of RzC. Catalytic activity was diminished or eliminated at sub-millimolar MgCl2 concentrations for ribozymes with weakened or deleted tertiary interactions. Eadie-Hofstee analysis revealed that the stabilized and non-stabilized ribozymes bind their substrates with equivalent affinities, suggesting that differences in observed activity are not the result of diminished binding. Some of the stabilized and non-stabilized ribozymes appear to fold into a heterogeneous collection of conformers, only a subset of which are catalytically active. Conclusion Hammerhead ribozymes with the "type III" topology can be converted to a tertiary, trans

  10. Structure of an anti-HIV-1 hammerhead ribozyme complex with a 17-mer DNA substrate analog of HIV-1 gag RNA and a mechanism for the cleavage reaction: 750 MHz NMR and computer experiments

    Science.gov (United States)

    Ojha, R. P.; Dhingra, M. M.; Sarma, M. H.; Myer, Y. P.; Setlik, R. F.; Shibata, M.; Kazim, A. L.; Ornstein, R. L.; Rein, R.; Turner, C. J.; hide

    1997-01-01

    The structure of an anti-HIV-1 ribozyme-DNA abortive substrate complex was investigated by 750 MHz NMR and computer modeling experiments. The ribozyme was a chimeric molecule with 30 residues-18 DNA nucleotides, and 12 RNA residues in the conserved core. The DNA substrate analog had 17 residues. The chimeric ribozyme and the DNA substrate formed a shortened ribozyme-abortive substrate complex of 47 nucleotides with two DNA stems (stems I and III) and a loop consisting of the conserved core residues. Circular dichroism spectra showed that the DNA stems assume A-family conformation at the NMR concentration and a temperature of 15 degrees C, contrary to the conventional wisdom that DNA duplexes in aqueous solution populate entirely in the B-form. It is proposed that the A-family RNA residues at the core expand the A-family initiated at the core into the DNA stems because of the large free energy requirement for the formation of A/B junctions. Assignments of the base H8/H6 protons and H1' of the 47 residues were made by a NOESY walk. In addition to the methyl groups of all T's, the imino resonances of stems I and III and AH2's were assigned from appropriate NOESY walks. The extracted NMR data along with available crystallographic data, were used to derive a structural model of the complex. Stems I and III of the final model displayed a remarkable similarity to the A form of DNA; in stem III, a GC base pair was found to be moving into the floor of the minor groove defined by flanking AT pairs; data suggest the formation of a buckled rhombic structure with the adjacent pair; in addition, the base pair at the interface of stem III and the loop region displayed deformed geometry. The loop with the catalytic core, and the immediate region of the stems displayed conformational multiplicity within the NMR time scale. A catalytic mechanism for ribozyme action based on the derived structure, and consistent with biochemical data in the literature, is proposed. The complex

  11. Hammerhead ribozyme activity and oligonucleotide duplex stability in mixed solutions of water and organic compounds

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    Shu-ichi Nakano

    2014-01-01

    Full Text Available Nucleic acids are useful for biomedical targeting and sensing applications in which the molecular environment is different from that of a dilute aqueous solution. In this study, the influence of various types of mixed solutions of water and water-soluble organic compounds on RNA was investigated by measuring the catalytic activity of the hammerhead ribozyme and the thermodynamic stability of an oligonucleotide duplex. The compounds with a net neutral charge, such as poly(ethylene glycol, small primary alcohols, amide compounds, and aprotic solvent molecules, added at high concentrations changed the ribozyme-catalyzed RNA cleavage rate, with the magnitude of the effect dependent on the NaCl concentration. These compounds also changed the thermodynamic stability of RNA base pairs of an oligonucleotide duplex and its dependence on the NaCl concentration. Specific interactions with RNA molecules and reduced water activity could account for the inhibiting effects on the ribozyme catalysis and destabilizing effects on the duplex stability. The salt concentration dependence data correlated with the dielectric constant, but not with water activity, viscosity, and the size of organic compounds. This observation suggests the significance of the dielectric constant effects on the RNA reactions under molecular crowding conditions created by organic compounds.

  12. Evidence for a hydroxide ion bridging two magnesium ions at the active site of the hammerhead ribozyme.

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    Hermann, T; Auffinger, P; Scott, W G; Westhof, E

    1997-09-01

    In the presence of magnesium ions, cleavage by the hammerhead ribozyme RNA at a specific residue leads to 2'3'-cyclic phosphate and 5'-OH extremities. In the cleavage reaction an activated ribose 2'-hydroxyl group attacks its attached 3'-phosphate. Molecular dynamics simulations of the crystal structure of the hammerhead ribozyme, obtained after flash-freezing of crystals under conditions where the ribozyme is active, provide evidence that a mu-bridging OH-ion is located between two Mg2+ions close to the cleavable phosphate. Constrained simulations show further that a flip from the C3'- endo to the C2'- endo conformation of the ribose at the cleavable phosphate brings the 2'-hydroxyl in proximity to both the attacked phosphorous atom and the mu-bridging OH-ion. Thus, the simulations lead to a detailed new insight into the mechanism of hammerhead ribozyme cleavage where a mu-hydroxo bridged magnesium cluster, located on the deep groove side, provides an OH-ion that is able to activate the 2'-hydroxyl nucleophile after a minor and localized conformational change in the RNA.

  13. Antiviral Hammerhead Ribozymes Are Effective for Developing Transgenic Suppression of Chikungunya Virus in Aedes aegypti Mosquitoes

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    Priya Mishra

    2016-06-01

    Full Text Available The chikungunya virus (CHIKV is an emerging pathogen with widespread distribution in regions of Africa, India, and Asia that threatens to spread into temperate climates with the introduction of its major vector, Aedes albopictus. CHIKV causes a disease frequently misdiagnosed as dengue fever, with potentially life-threatening symptoms that can result in a longer-term debilitating arthritis. The increasing risk of spread from endemic regions via human travel and commerce and the current absence of a vaccine put a significant proportion of the world population at risk for this disease. In this study we designed and tested hammerhead ribozymes (hRzs targeting CHIKV structural protein genes of the RNA genome as potential antivirals both at the cellular and in vivo level. We employed the CHIKV strain 181/25, which exhibits similar infectivity rates in both Vero cell cultures and mosquitoes. Virus suppression assay performed on transformed Vero cell clones of all seven hRzs demonstrated that all are effective at inhibiting CHIKV in Vero cells, with hRz #9 and #14 being the most effective. piggyBac transformation vectors were constructed using the Ae. aegypti t-RNAval Pol III promoted hRz #9 and #14 effector genes to establish a total of nine unique transgenic Higgs White Eye (HWE Ae. aegypti lines. Following confirmation of transgene expression by real-time polymerase chain reaction (RT-PCR, comparative TCID50-IFA analysis, in situ Immuno-fluorescent Assays (IFA and analysis of salivary CHIKV titers demonstrated effective suppression of virus replication at 7 dpi in heterozygous females of each of these transgenic lines compared with control HWE mosquitoes. This report provides a proof that appropriately engineered hRzs are powerful antiviral effector genes suitable for population replacement strategies

  14. Origin of mutational effects at the C3 and G8 positions on hammerhead ribozyme catalysis from molecular dynamics simulations.

    Science.gov (United States)

    Lee, Tai-Sung; York, Darrin M

    2008-06-11

    A series of ten 60 ns molecular dynamics (MD) simulations of the native and mutated full length hammerhead ribozymes in the reactant state and in an activated precursor state (G8:2'OH deprotonated) are reported. Mutant simulations include the C3U, G8A, and G8I single mutants and a C3U/G8A double mutant that exhibits an experimental rescue effect. The results provide critical details into the origin of the observed mutation effects and support a mechanism where the 2'OH of G8 acts as a general acid catalyst that is held in position through Watson-Crick hydrogen bonding between G8 and C3.

  15. Structural and catalytic effects of an invariant purine substitution in the hammerhead ribozyme: implications for the mechanism of acid-base catalysis.

    Science.gov (United States)

    Schultz, Eric P; Vasquez, Ernesto E; Scott, William G

    2014-09-01

    The hammerhead ribozyme catalyzes RNA cleavage via acid-base catalysis. Whether it does so by general acid-base catalysis, in which the RNA itself donates and abstracts protons in the transition state, as is typically assumed, or by specific acid-base catalysis, in which the RNA plays a structural role and proton transfer is mediated by active-site water molecules, is unknown. Previous biochemical and crystallographic experiments implicate an invariant purine in the active site, G12, as the general base. However, G12 may play a structural role consistent with specific base catalysis. To better understand the role of G12 in the mechanism of hammerhead catalysis, a 2.2 Å resolution crystal structure of a hammerhead ribozyme from Schistosoma mansoni with a purine substituted for G12 in the active site of the ribozyme was obtained. Comparison of this structure (PDB entry 3zd4), in which A12 is substituted for G, with three previously determined structures that now serve as important experimental controls, allows the identification of structural perturbations that are owing to the purine substitution itself. Kinetic measurements for G12 purine-substituted schistosomal hammerheads confirm a previously observed dependence of rate on the pK(a) of the substituted purine; in both cases inosine, which is similar to G in pK(a) and hydrogen-bonding properties, is unexpectedly inactive. Structural comparisons indicate that this may primarily be owing to the lack of the exocyclic 2-amino group in the G12A and G12I substitutions and its structural effect upon both the nucleotide base and phosphate of A9. The latter involves the perturbation of a previously identified and well characterized metal ion-binding site known to be catalytically important in both minimal and full-length hammerhead ribozyme sequences. The results permit it to be suggested that G12 plays an important role in stabilizing the active-site structure. This result, although not inconsistent with the potential

  16. Model for general acid-base catalysis by the hammerhead ribozyme: pH-activity relationships of G8 and G12 variants at the putative active site.

    Science.gov (United States)

    Han, Joonhee; Burke, John M

    2005-05-31

    We have used nucleobase substitution and kinetic analysis to test the hypothesis that hammerhead catalysis occurs by a general acid-base mechanism, in which nucleobases are directly involved in deprotonation of the attacking 2'-hydroxyl group and protonation of the 5'-oxygen that serves as the leaving group in the cleavage reaction. We demonstrate that simultaneous substitution of two important nucleobases, G8 and G12, with 2,6-diaminopurine shifts the pH optimum of the cleavage reaction from greater than 9.5 to approximately 6.8 in two different hammerhead constructs. Controls involving substitution with other nucleobases and combinations of nucleobases at G5, G8, and/or G12 do not show this behavior. The observed changes in the pH-rate behavior are consistent with a mechanism in which N1 protonation-deprotonation events of guanine or 2,6-diaminopurine at positions 8 and 12 are essential for catalysis. Further support for the participation of G8 and G12 comes from photochemical cross-linking experiments, which show that G8 and G12 can stack upon the two substrate nucleobases at the reactive linkage, G(or U)1.1 and C17 (Heckman, J. E., Lambert, D., and Burke, J. M. (2005) Photocrosslinking detects a compact active structure of the hammerhead ribozyme, Biochemistry 44, 4148-4156). Together, these results support a model in which the hammerhead undergoes a transient conformational change into a catalytically active structure, in which stacking of G8 and G12 upon the nucleobases spanning the cleavage site provides an appropriate architecture for general acid-base catalysis. The hammerhead and hairpin ribozymes may share similarities in the organization of their active sites and their catalytic mechanism.

  17. K(+)-Responsive off-to-on switching of hammerhead ribozyme through dual G-quadruplex formation requiring no heating and cooling treatment.

    Science.gov (United States)

    Yamaoki, Yudai; Nagata, Takashi; Mashima, Tsukasa; Katahira, Masato

    Functional RNAs that switch their activities in response to K(+) may sense the intracellular (100 mM) and extracellular (5 mM) K(+) concentrations and regulate their functions accordingly. Previously, we developed a quadruplex hammerhead ribozyme (QHR) whose conformational change, from a duplex to a G-quadruplex, triggered by K(+) results in expression of the activity. However, this QHR required heating and cooling treatment (annealing) to induce the K(+)-responsive conformational change and activity. Here, we developed a new quadruplex hammerhead ribozyme (QHR) system that does not require annealing to induce the K(+)-responsive conformational change and activity. This system is composed of QHR and a G-quadruplex-forming complementary DNA strand (QCS). In the absence of K(+), QCS formed a duplex with QHR, which suppressed the residual activity. Upon elevation of the K(+) concentration, QCS dissociated from QHR was trapped in a G-quadruplex, and then QHR could form a G-quadruplex and exerted the activity. The 11.6-fold higher activity was induced by K(+) with an EC50 value of 23 mM, but not by Na(+), which is desirable when the activity switching between the intra-/extracellular environment is aimed at. This is the first report of the activation of functional RNA through a 'dual G-quadruplex formation system'. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Secondary structure in solution of two anti-HIV-1 hammerhead ribozymes as investigated by two-dimensional 1H 500 MHz NMR spectroscopy in water

    Science.gov (United States)

    Sarma, R. H.; Sarma, M. H.; Rein, R.; Shibata, M.; Setlik, R. S.; Ornstein, R. L.; Kazim, A. L.; Cairo, A.; Tomasi, T. B.

    1995-01-01

    Two hammerhead chimeric RNA/DNA ribozymes (HRz) were synthesized in pure form. Both were 30 nucleotides long, and the sequences were such that they could be targeted to cleave the HIV-1 gag RNA. Named HRz-W and HRz-M, the former had its invariable core region conserved, the latter had a uridine in the invariable region replaced by a guanine. Their secodary structures were determined by 2D NOESY 1H 500 MHz NMR spectroscopy in 90% water and 10% D2(0), following the imino protons. The data show that both HRz-M and HRz-W form identical secondary structures with stem regions consisting of continuous stacks of AT and GT pairs. An energy minimized computer model of this stem region is provided. The results suggest that the loss of catalytic activity that is known to result when an invariant core residue is replaced is not related to the secondary structure of the ribozymes in the absence of substrate.

  19. Fast ribozyme cleavage releases transcripts from RNA polymerase II and aborts co-transcriptional pre-mRNA processing

    OpenAIRE

    Fong, Nova; Ohman, Marie; Bentley, David L.

    2009-01-01

    SUMMARY We investigated whether a continuous transcript is necessary for co-transcriptional pre-mRNA processing. Cutting an intron with the fast-cleaving hepatitis ? ribozyme, but not the slower hammerhead, inhibited splicing. Exon tethering to RNA pol II therefore cannot rescue splicing of a transcript severed by a ribozyme that cleaves rapidly relative to splicing. Ribozyme cutting also released cap-binding complex (CBC) from the gene, suggesting that exon 1 is not tethered. Unexpectedly, c...

  20. Spiegelzymes® mirror-image hammerhead ribozymes and mirror-image DNAzymes, an alternative to siRNAs and microRNAs to cleave mRNAs in vivo?

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    Eliza Wyszko

    Full Text Available With the discovery of small non-coding RNA (ncRNA molecules as regulators for cellular processes, it became intriguing to develop technologies by which these regulators can be applied in molecular biology and molecular medicine. The application of ncRNAs has significantly increased our knowledge about the regulation and functions of a number of proteins in the cell. It is surprising that similar successes in applying these small ncRNAs in biotechnology and molecular medicine have so far been very limited. The reasons for these observations may lie in the high complexity in which these RNA regulators function in the cells and problems with their delivery, stability and specificity. Recently, we have described mirror-image hammerhead ribozymes and DNAzymes (Spiegelzymes® which can sequence-specifically hydrolyse mirror-image nucleic acids, such as our mirror-image aptamers (Spiegelmers discovered earlier. In this paper, we show for the first time that Spiegelzymes are capable of recognising complementary enantiomeric substrates (D-nucleic acids, and that they efficiently hydrolyse them at submillimolar magnesium concentrations and at physiologically relevant conditions. The Spiegelzymes are very stable in human sera, and do not require any protein factors for their function. They have the additional advantages of being non-toxic and non-immunogenic. The Spiegelzymes can be used for RNA silencing and also as therapeutic and diagnostic tools in medicine. We performed extensive three-dimensional molecular modelling experiments with mirror-image hammerhead ribozymes and DNAzymes interacting with D-RNA targets. We propose a model in which L/D-double helix structures can be formed by natural Watson-Crick base pairs, but where the nucleosides of one of the two strands will occur in an anticlinal conformation. Interestingly enough, the duplexes (L-RNA/D-RNA and L-DNA/D-RNA in these models can show either right- or left-handedness. This is a very new

  1. Ultrasensitive monitoring of ribozyme cleavage product using molecular-beacon-ligation system

    Institute of Scientific and Technical Information of China (English)

    MENG XiangXian; TANG ZhiWen; WANG KeMin; TAN WeiHong; YANG XiaoHai; LI Jun; GUO QiuPing

    2007-01-01

    This paper reports a new approach to detect ribozyme cleavage product based on the molecular- beacon-ligation system. The molecular beacon, designed in such a way that one-half of its loop is complementary to ribozyme cleavage product, is used to monitor ligation process of RNA/DNA complex in a homogeneous solution and to convert directly cleavage product information into fluorescence signal. The method need not label ribozyme and ribozyme substrate, which is fast, simple and ultrasensitive for detection of cleavage product. Detection limit of the assay is 0.05 nmol/L. The cleavage product of hammerhead ribozyme against hepatitis C virus RNA (HCV-RNA) was detected perfectly based on this assay. Owing to its ultrasensitivity, excellent specificity, convenience and fidelity, this method might hold out great promise in ribozyme reaction and ribozyme gene therapy.

  2. Improved design of hammerhead ribozyme for selective digestion of target RNA through recognition of site-specific adenosine-to-inosine RNA editing

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    Fukuda, Masatora; Kurihara, Kei; Yamaguchi, Shota; Oyama, Yui; Deshimaru, Masanobu

    2014-01-01

    Adenosine-to-inosine (A-to-I) RNA editing is an endogenous regulatory mechanism involved in various biological processes. Site-specific, editing-state–dependent degradation of target RNA may be a powerful tool both for analyzing the mechanism of RNA editing and for regulating biological processes. Previously, we designed an artificial hammerhead ribozyme (HHR) for selective, site-specific RNA cleavage dependent on the A-to-I RNA editing state. In the present work, we developed an improved strategy for constructing a trans-acting HHR that specifically cleaves target editing sites in the adenosine but not the inosine state. Specificity for unedited sites was achieved by utilizing a sequence encoding the intrinsic cleavage specificity of a natural HHR. We used in vitro selection methods in an HHR library to select for an extended HHR containing a tertiary stabilization motif that facilitates HHR folding into an active conformation. By using this method, we successfully constructed highly active HHRs with unedited-specific cleavage. Moreover, using HHR cleavage followed by direct sequencing, we demonstrated that this ribozyme could cleave serotonin 2C receptor (HTR2C) mRNA extracted from mouse brain, depending on the site-specific editing state. This unedited-specific cleavage also enabled us to analyze the effect of editing state at the E and C sites on editing at other sites by using direct sequencing for the simultaneous quantification of the editing ratio at multiple sites. Our approach has the potential to elucidate the mechanism underlying the interdependencies of different editing states in substrate RNA with multiple editing sites. PMID:24448449

  3. Improved design of hammerhead ribozyme for selective digestion of target RNA through recognition of site-specific adenosine-to-inosine RNA editing.

    Science.gov (United States)

    Fukuda, Masatora; Kurihara, Kei; Yamaguchi, Shota; Oyama, Yui; Deshimaru, Masanobu

    2014-03-01

    Adenosine-to-inosine (A-to-I) RNA editing is an endogenous regulatory mechanism involved in various biological processes. Site-specific, editing-state-dependent degradation of target RNA may be a powerful tool both for analyzing the mechanism of RNA editing and for regulating biological processes. Previously, we designed an artificial hammerhead ribozyme (HHR) for selective, site-specific RNA cleavage dependent on the A-to-I RNA editing state. In the present work, we developed an improved strategy for constructing a trans-acting HHR that specifically cleaves target editing sites in the adenosine but not the inosine state. Specificity for unedited sites was achieved by utilizing a sequence encoding the intrinsic cleavage specificity of a natural HHR. We used in vitro selection methods in an HHR library to select for an extended HHR containing a tertiary stabilization motif that facilitates HHR folding into an active conformation. By using this method, we successfully constructed highly active HHRs with unedited-specific cleavage. Moreover, using HHR cleavage followed by direct sequencing, we demonstrated that this ribozyme could cleave serotonin 2C receptor (HTR2C) mRNA extracted from mouse brain, depending on the site-specific editing state. This unedited-specific cleavage also enabled us to analyze the effect of editing state at the E and C sites on editing at other sites by using direct sequencing for the simultaneous quantification of the editing ratio at multiple sites. Our approach has the potential to elucidate the mechanism underlying the interdependencies of different editing states in substrate RNA with multiple editing sites.

  4. Efficient transfer of synthetic ribozymes into cells using hemagglutinating virus of Japan (HVJ)-cationic liposomes. Application for ribozymes that target human t-cell leukemia virus type I tax/rex mRNA.

    Science.gov (United States)

    Kitajima, I; Hanyu, N; Soejima, Y; Hirano, R; Arahira, S; Yamaoka, S; Yamada, R; Maruyama, I; Kaneda, Y

    1997-10-24

    We investigated the usefulness of ribozymes in inhibiting the expression of human T-cell leukemia virus type I (HTLV-I) gene. Two hammerhead ribozymes that were against HTLV-I rex (RR) and tax (TR) mRNA were synthesized. Both ribozymes were sequence-specific in the in vitro cleavage analysis of run-off transcripts from tax/rex cDNA. Intracellular activities of the ribozymes were studied in HTLV-I tax cDNA-transfected rat embryonic fibroblasts (Rat/Tax cells), which expressed the Tax but not Rex. Ribozymes were delivered into cells using anionic or cationic liposomes fused with hemagglutinating virus of Japan (HVJ). Cellular uptake of ribozymes complexed with HVJ-cationic liposomes was 15-20 times higher cellular uptake than naked ribozymes, and 4-5 times higher than that of ribozymes complexed with HVJ-anionic liposomes. HVJ-cationic liposomes promoted accumulation of ribozymes in cytoplasm and accelerated transport to the nucleus. Tax protein levels were decreased about 95% and were five times lower when the same amount of TR was introduced into the cells using HVJ-cationic, rather than HVJ-anionic liposomes. Inactive ribozyme and tax antisense oligodeoxynucleotides reduced Tax expression by about 20%, whereas RR and tax sense oligodeoxynucleotides had no effect. These results suggest that the ribozymes' effect against tax mRNA was sequence-specific, and HVJ-cationic liposomes can be useful for intracellular introduction of ribozymes.

  5. Structural investigation of a high-affinity MnII binding site in the hammerhead ribozyme by EPR spectroscopy and DFT calculations. Effects of neomycin B on metal-ion binding.

    Science.gov (United States)

    Schiemann, Olav; Fritscher, Jörg; Kisseleva, Natalja; Sigurdsson, Snorri Th; Prisner, Thomas F

    2003-10-06

    Electron paramagnetic resonance spectroscopy and density functional theory methods were used to study the structure of a single, high-affinity Mn(II) binding site in the hammerhead ribozyme. This binding site exhibits a dissociation constant Ke of 4.4 microM in buffer solutions containing 1 M NaCl, as shown by titrations monitored by continuous wave (cw) EPR. A combination of electron spin echo envelope modulation (ESEEM) and hyperfine sublevel correlation (HYSCORE) experiments revealed that the paramagnetic manganese(II) ion in this binding site is coupled to a single nitrogen atom with a quadrupole coupling constant kappa of 0.7 MHz, an asymmetry parameter eta of 0.4, and an isotropic hyperfine coupling constant of Aiso(14N)=2.3 MHz. All three EPR parameters are sensitive to the arrangement of the Mn(II) ligand sphere and can therefore be used to determine the structure of the binding site. A possible location for this binding site may be at the G10.1, A9 site found to be occupied by Mn(II) in crystals (MacKay et al., Nature 1994, 372, 68 and Scott et al., Science 1996, 274, 2065). To determine whether the structure of the binding site is the same in frozen solution, we performed DFT calculations for the EPR parameters, based on the structure of the Mn(II) site in the crystal. Computations with the BHPW91 density function in combination with a 9s7p4d basis set for the manganese(II) center and the Iglo-II basis set for all other atoms yielded values of kappa(14N)=+0.80 MHz, eta=0.324, and Aiso(14N)=+2.7 MHz, in excellent agreement with the experimentally obtained EPR parameters, which suggests that the binding site found in the crystal and in frozen solution are the same. In addition, we demonstrated by EPR that Mn(II) is released from this site upon binding of the aminoglycoside antibiotic neomycin B (Kd=1.2 microM) to the hammerhead ribozyme. Neomycin B has previously been shown to inhibit the catalytic activity of this ribozyme (Uhlenbeck et al., Biochemistry

  6. Catalytic strategies of self-cleaving ribozymes.

    Science.gov (United States)

    Cochrane, Jesse C; Strobel, Scott A

    2008-08-01

    [Structure: see text]. Five naturally occurring nucleolytic ribozymes have been identified: the hammerhead, hairpin, glmS, hepatitis delta virus (HDV), and Varkud satellite (VS) ribozymes. All of these RNA enzymes catalyze self-scission of the RNA backbone using a chemical mechanism equivalent to that of RNase A. RNase A uses four basic strategies to promote this reaction: geometric constraints, activation of the nucleophile, transition-state stabilization, and leaving group protonation. In this Account, we discuss the current thinking on how nucleolytic ribozymes harness RNase A's four sources of catalytic power. The geometry of the phosphodiester cleavage reaction constrains the nucleotides flanking the scissile phosphate so that they are unstacked from a canonical A-form helix and thus require alternative stabilization. Crystal structures and mutational analysis reveal that cross-strand base pairing, along with unconventional stacking and tertiary hydrogen-bonding interactions, work to stabilize the splayed conformation in nucleolytic ribozymes. Deprotonation of the 2'-OH nucleophile greatly increases its nucleophilicity in the strand scission reaction. Crystal structures of the hammerhead, hairpin, and glmS ribozymes reveal the N1 of a G residue within hydrogen-bonding distance of the 2'-OH. In each case, this residue has also been shown to be important for catalysis. In the HDV ribozyme, a hydrated magnesium has been implicated as the general base. Catalysis by the VS ribozyme requires both an A and a G, but the precise role of either has not been elucidated. Enzymes can lower the energy of a chemical reaction by binding more tightly to the transition state than to the ground states. Comparison of the hairpin ground- and transition-state mimic structures reveal greater hydrogen bonding to the transition-state mimic structure, suggesting transition-state stabilization as a possible catalytic strategy. However, the hydrogen-bonding pattern in the glmS ribozyme

  7. Technology evaluation: HIV ribozyme gene therapy, Gene Shears Pty Ltd.

    Science.gov (United States)

    de Feyter, R; Li, P

    2000-06-01

    Ribozymes (catalytic RNAs) can be made to specifically cleave target RNAs that are involved in disease conditions and therefore have potential as therapeutic agents. Gene Shears Pty Ltd is developing hammerhead ribozyme technology for therapy against HIV infection, targeting either the tat gene or the RNA packaging sequence (Psi) of HIV. These ribozymes have been expressed from constructs that were introduced into hematopoietic cells in culture, thereby protecting the cells against viral infection. Two phase I clinical trials are underway to test the safety and feasibility of the approach with the anti-tat ribozyme in human subjects.

  8. A 1.9 Å Crystal Structure of the HDV Ribozyme Precleavage Suggests both Lewis Acid and General Acid Mechanisms Contribute to Phosphodiester Cleavage

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Jui-Hui; Yajima, Rieko; Chadalavada, Durga M.; Chase, Elaine; Bevilacqua, Philip C.; Golden, Barbara L. (Purdue); (Penn)

    2010-11-01

    The hepatitis delta virus (HDV) ribozyme and HDV-like ribozymes are self-cleaving RNAs found throughout all kingdoms of life. These RNAs fold into a double-nested pseudoknot structure and cleave RNA, yielding 2{prime},3{prime}-cyclic phosphate and 5{prime}-hydroxyl termini. The active site nucleotide C75 has a pK{sub a} shifted >2 pH units toward neutrality and has been implicated as a general acid/base in the cleavage reaction. An active site Mg{sup 2+} ion that helps activate the 2{prime}-hydroxyl for nucleophilic attack has been characterized biochemically; however, this ion has not been visualized in any previous structures. To create a snapshot of the ribozyme in a state poised for catalysis, we have crystallized and determined the structure of the HDV ribozyme bound to an inhibitor RNA containing a deoxynucleotide at the cleavage site. This structure includes the wild-type C75 nucleotide and Mg{sup 2+} ions, both of which are required for maximal ribozyme activity. This structure suggests that the position of C75 does not change during the cleavage reaction. A partially hydrated Mg{sup 2+} ion is also found within the active site where it interacts with a newly resolved G {center_dot} U reverse wobble. Although the inhibitor exhibits crystallographic disorder, we modeled the ribozyme-substrate complex using the conformation of the inhibitor strand observed in the hammerhead ribozyme. This model suggests that the pro-RP oxygen of the scissile phosphate and the 2{prime}-hydroxyl nucleophile are inner-sphere ligands to the active site Mg{sup 2+} ion. Thus, the HDV ribozyme may use a combination of metal ion Lewis acid and nucleobase general acid strategies to effect RNA cleavage.

  9. Structure-based mechanistic insights into catalysis by small self-cleaving ribozymes.

    Science.gov (United States)

    Ren, Aiming; Micura, Ronald; Patel, Dinshaw J

    2017-12-01

    Small self-cleaving ribozymes are widely distributed in nature and are essential for rolling-circle-based replication of satellite and pathogenic RNAs. Earlier structure-function studies on the hammerhead, hairpin, glmS, hepatitis delta virus and Varkud satellite ribozymes have provided insights into their overall architecture, their catalytic active site organization, and the role of nearby nucleobases and hydrated divalent cations in facilitating general acid-base and electrostatic-mediated catalysis. This review focuses on recent structure-function research on active site alignments and catalytic mechanisms of the Rzb hammerhead ribozyme, as well as newly-identified pistol, twister and twister-sister ribozymes. In contrast to an agreed upon mechanistic understanding of self-cleavage by Rzb hammerhead and pistol ribozymes, there exists a divergence of views as to the cleavage site alignments and catalytic mechanisms adopted by twister and twister-sister ribozymes. One approach to resolving this conundrum would be to extend the structural studies from currently available pre-catalytic conformations to their transition state mimic vanadate counterparts for both ribozymes. Copyright © 2017. Published by Elsevier Ltd.

  10. Molecular trade-offs in RNA ligases affected the modular emergence of complex ribozymes at the origin of life.

    Science.gov (United States)

    Dhar, Nisha; Weinberg, Marc S; Michod, Richard E; Durand, Pierre M

    2017-09-01

    In the RNA world hypothesis complex, self-replicating ribozymes were essential. For the emergence of an RNA world, less is known about the early processes that accounted for the formation of complex, long catalysts from small passively formed molecules. The functional role of small sequences has not been fully explored and, here, a possible role for smaller ligases is demonstrated. An established RNA polymerase model, the R18, was truncated from the 3' end to generate smaller molecules. All the molecules were investigated for self-ligation functions with a set of oligonucleotide substrates without predesigned base pairing. The smallest molecule that exhibited self-ligation activity was a 40-nucleotide RNA. It also demonstrated the greatest functional flexibility as it was more general in the kinds of substrates it ligated to itself although its catalytic efficiency was the lowest. The largest ribozyme (R18) ligated substrates more selectively and with greatest efficiency. With increase in size and predicted structural stability, self-ligation efficiency improved, while functional flexibility decreased. These findings reveal that molecular size could have increased from the activity of small ligases joining oligonucleotides to their own end. In addition, there is a size-associated molecular-level trade-off that could have impacted the evolution of RNA-based life.

  11. Molecular trade-offs in RNA ligases affected the modular emergence of complex ribozymes at the origin of life

    Science.gov (United States)

    Dhar, Nisha; Weinberg, Marc S.; Michod, Richard E.; Durand, Pierre M.

    2017-09-01

    In the RNA world hypothesis complex, self-replicating ribozymes were essential. For the emergence of an RNA world, less is known about the early processes that accounted for the formation of complex, long catalysts from small passively formed molecules. The functional role of small sequences has not been fully explored and, here, a possible role for smaller ligases is demonstrated. An established RNA polymerase model, the R18, was truncated from the 3' end to generate smaller molecules. All the molecules were investigated for self-ligation functions with a set of oligonucleotide substrates without predesigned base pairing. The smallest molecule that exhibited self-ligation activity was a 40-nucleotide RNA. It also demonstrated the greatest functional flexibility as it was more general in the kinds of substrates it ligated to itself although its catalytic efficiency was the lowest. The largest ribozyme (R18) ligated substrates more selectively and with greatest efficiency. With increase in size and predicted structural stability, self-ligation efficiency improved, while functional flexibility decreased. These findings reveal that molecular size could have increased from the activity of small ligases joining oligonucleotides to their own end. In addition, there is a size-associated molecular-level trade-off that could have impacted the evolution of RNA-based life.

  12. Hairpin Ribozyme Genes Curtail Alcohol Drinking: from Rational Design to in vivo Effects in the Rat

    Directory of Open Access Journals (Sweden)

    Amalia Sapag

    2016-01-01

    Full Text Available Ribozyme genes were designed to reduce voluntary alcohol drinking in a rat model of alcohol dependence. Acetaldehyde generated from alcohol in the liver is metabolized by the mitochondrial aldehyde dehydrogenase (ALDH2 such that diminishing ALDH2 activity leads to the aversive effects of blood acetaldehyde upon alcohol intake. A stepwise approach was followed to design genes encoding ribozymes targeted to the rat ALDH2 mRNA. In vitro studies of accessibility to oligonucleotides identified suitable target sites in the mRNA, one of which fulfilled hammerhead and hairpin ribozyme requirements (CGGUC. Ribozyme genes delivered in plasmid constructs were tested in rat cells in culture. While the hairpin ribozyme reduced ALDH2 activity 56% by cleavage and blockade (P < 0.0001, the hammerhead ribozyme elicited minor effects by blockade. The hairpin ribozyme was tested in vivo by adenoviral gene delivery to UChB alcohol drinker rats. Ethanol intake was curtailed 47% for 34 days (P < 0.0001, while blood acetaldehyde more than doubled upon ethanol administration and ALDH2 activity dropped 25% in liver homogenates, not affecting other ALDH isoforms. Thus, hairpin ribozymes targeted to 16 nt in the ALDH2 mRNA provide durable and specific effects in vivo, representing an improvement on previous work and encouraging development of gene therapy for alcoholism.

  13. Studying Hammerheads in Hawaii

    Science.gov (United States)

    Handler, Alex; Duncan, Kanesa

    2006-01-01

    In this article, the author discusses the High School Scalloped Hammerhead Shark Tagging Program in Hawaii which is an example of a successful partnership research collaboration. High school students and teachers worked with biologists from the University of Hawaii-Manoa (UHM) to conduct research on the life history of scalloped hammerhead sharks…

  14. Group I intron ribozymes

    DEFF Research Database (Denmark)

    Nielsen, Henrik

    2012-01-01

    Group I intron ribozymes constitute one of the main classes of ribozymes and have been a particularly important model in the discovery of key concepts in RNA biology as well as in the development of new methods. Compared to other ribozyme classes, group I intron ribozymes display considerable......, the intronic products of these pathways have the potential to integrate into targets and to form various types of circular RNA molecules. Thus, group I intron ribozymes and associated elements found within group I introns is a rich source of biological phenomena. This chapter provides a strategy and protocols...

  15. Application of computational technologies to ribozyme biotechnology products

    Science.gov (United States)

    Christoffersen, Ralph E.; McSwiggen, James; Konings, Danielle

    1994-07-01

    Ribozymes are RNA molecules that act enzymatically to cleave other RNA molecules. The cleavage reaction requires the binding of ribozyme to specific sites on the target RNA through (mostly) Watson-Crick base-pairing interactions. Association of ribozyme with target completes a three-dimensional ribozyme/target complex which results in cleavage of the target RNA. We are employing both computational and experimental approaches to identify sites on target RNA molecules that are open to ribozyme attack and to determine which ribozymes are most active against those sites. Two types of computational technologies are available for aiding in the identification of target sites and design of active ribozymes. First, DNA/RNA sequence analysis software is employed to identify sequence motifs necessary for ribozyme cleavage and to look for sequence conservation between different sources of the target organism so that ribozymes with the broadest possible target range can be designed. Second, RNA folding algorithms are employed to predict the secondary structure of both ribozyme and target RNA in an attempt to identify combinations of ribozyme and target site that will successfully associate prior to ribozyme cleavage. The RNA folding algorithms utilize a set of thermodynamic parameters obtained from measurements on short RNA duplexes; while these rules give reasonable predictions of secondary structure for a small set of highly structured RNAs, they remain largely untested for predicting the structure of messenger RNAs. This paper outlines the current status of designing ribozymes that fold correctly and of locating target sites that are sufficiently unfolded to allow ribozyme cleavage.

  16. Molecular characterization of a new member of the lariat capping twin-ribozyme introns

    DEFF Research Database (Denmark)

    Tang, Yunjia; Nielsen, Henrik; Masquida, Benoît

    2014-01-01

    BACKGROUND: Twin-ribozyme introns represent a complex class of mobile group I introns that harbour a lariat capping (LC) ribozyme and a homing endonuclease gene embedded in a conventional self-splicing group I ribozyme (GIR2). Twin-ribozyme introns have so far been confined to nucleolar DNA...... splicing and homing endonuclease mRNA maturation. We found Allovahlkampfia GIR2 to be a typical group IC1 splicing ribozyme responsible for addition of the exogenous guanosine cofactor (exoG), exon ligation and circularization of intron RNA. The Allovahlkampfia LC ribozyme, by contrast, represents...... an efficient self-cleaving ribozyme that generates a small 2',5' lariat cap at the 5' end of the homing endonuclease mRNA, and thus contributes to intron mobility. CONCLUSIONS: The discovery of a twin-ribozyme intron in a member of Heterolobosea expands the distribution pattern of LC ribozymes. We identify...

  17. Ionic interactions and the global conformations of the hammerhead ribozyme

    DEFF Research Database (Denmark)

    Bassi, G S; Møllegaard, N E; Murchie, A I

    1995-01-01

    by the remaining helix I. In the probable active conformation, a small angle is subtended between helices I and II. Using uranyl photocleavage, an ion binding site has been detected in the long single-stranded region. The folded conformation could generate a preactivation of the scissile bond to permit in...

  18. A Faster Triphosphorylation Ribozyme.

    Directory of Open Access Journals (Sweden)

    Gregory F Dolan

    Full Text Available In support of the RNA world hypothesis, previous studies identified trimetaphosphate (Tmp as a plausible energy source for RNA world organisms. In one of these studies, catalytic RNAs (ribozymes that catalyze the triphosphorylation of RNA 5'-hydroxyl groups using Tmp were obtained by in vitro selection. One ribozyme (TPR1 was analyzed in more detail. TPR1 catalyzes the triphosphorylation reaction to a rate of 0.013 min-1 under selection conditions (50 mM Tmp, 100 mM MgCl2, 22°C. To identify a triphosphorylation ribozyme that catalyzes faster triphosphorylation, and possibly learn about its secondary structure TPR1 was subjected to a doped selection. The resulting ribozyme, TPR1e, contains seven mutations relative to TPR1, displays a previously unidentified duplex that constrains the ribozyme's structure, and reacts at a 24-fold faster rate than the parent ribozyme. Under optimal conditions (150 mM Tmp, 650 mM MgCl2, 40°C, the triphosphorylation rate of TRP1e reaches 6.8 min-1.

  19. Eggplant Latent Viroid, the Candidate Type Species for a New Genus within the Family Avsunviroidae (Hammerhead Viroids)

    Science.gov (United States)

    Fadda, Z.; Daròs, J. A.; Fagoaga, C.; Flores, R.; Duran-Vila, N.

    2003-01-01

    Viroids, small circular RNAs that replicate independently and in most cases incite diseases in plants, are classified into the families Pospiviroidae, composed of species with a central conserved region (CCR) and without hammerhead ribozymes, and Avsunviroidae, composed of three members lacking CCR but able to self-cleave in both polarity strands through hammerhead ribozymes. Here we report the biological and molecular properties of Eggplant latent viroid (ELVd). Purified circular ELVd induces symptomless infections when inoculated into eggplant seedlings. ELVd can be transmitted horizontally and through seed. Sequencing 10 complete cDNA clones showed that ELVd is a circular RNA of 332 to 335 nucleotides with high variability. This RNA can adopt a quasi-rod-like secondary structure of minimal free energy and alternative foldings that permit formation of stable hammerhead structures in plus and minus strands. The ribozymes are active in vitro and, most likely, in vivo. Considering the ELVd properties to be intermediate between those of the two genera of family Avsunviroidae, we propose ELVd as the type species of a third genus with the name Elaviroid. PMID:12743309

  20. Distribution and movement of scalloped hammerhead Sphryna ...

    African Journals Online (AJOL)

    Knowledge of population distribution and movement is crucial for the conservation and management of shark species occurring in coastal waters. From 1984 to 2009, 641 scalloped hammerheads Sphyrna lewini, 1 342 smooth hammerheads Sphyrna zygaena and 1 352 unspecified hammerheads Sphyrna spp. were ...

  1. Catalytic Activities of Ribozymes and DNAzymes in Water and Mixed Aqueous Media

    Directory of Open Access Journals (Sweden)

    Shu-ichi Nakano

    2017-11-01

    Full Text Available Catalytic nucleic acids are regarded as potential therapeutic agents and biosensors. The catalytic activities of nucleic acid enzymes are usually investigated in dilute aqueous solutions, although the physical properties of the reaction environment inside living cells and that in the area proximal to the surface of biosensors in which they operate are quite different from those of pure water. The effect of the molecular environment is also an important focus of research aimed at improving and expanding nucleic acid function by addition of organic solvents to aqueous solutions. In this study, the catalytic activities of RNA and DNA enzymes (hammerhead ribozyme, 17E DNAzyme, R3C ribozyme, and 9DB1 DNAzyme were investigated using 21 different mixed aqueous solutions comprising organic compounds. Kinetic measurements indicated that these enzymes can display enhanced catalytic activity in mixed solutions with respect to the solution containing no organic additives. Correlation analyses revealed that the turnover rate of the reaction catalyzed by hammerhead ribozyme increased in a medium with a lower dielectric constant than water, and the turnover rate of the reaction catalyzed by 17E DNAzyme increased in conditions that increased the strength of DNA interactions. On the other hand, R3C ribozyme and 9DB1 DNAzyme displayed no significant turnover activity, but their single-turnover rates increased in many mixed solutions. Our data provide insight into the activity of catalytic nucleic acids under various conditions that are applicable to the medical and technology fields, such as in living cells and in biosensors.

  2. A widespread self-cleaving ribozyme class is revealed by bioinformatics.

    Science.gov (United States)

    Roth, Adam; Weinberg, Zasha; Chen, Andy G Y; Kim, Peter B; Ames, Tyler D; Breaker, Ronald R

    2014-01-01

    Ribozymes are noncoding RNAs that promote chemical transformations with rate enhancements approaching those of protein enzymes. Although ribozymes are likely to have been abundant during the RNA world era, only ten classes are known to exist among contemporary organisms. We report the discovery and analysis of an additional self-cleaving ribozyme class, called twister, which is present in many species of bacteria and eukarya. Nearly 2,700 twister ribozymes were identified that conform to a secondary structure consensus that is small yet complex, with three stems conjoined by internal and terminal loops. Two pseudoknots provide tertiary structure contacts that are critical for catalytic activity. The twister ribozyme motif provides another example of a natural RNA catalyst and calls attention to the potentially varied biological roles of this and other classes of widely distributed self-cleaving RNAs.

  3. Enhanced visual fields in hammerhead sharks.

    Science.gov (United States)

    McComb, D M; Tricas, T C; Kajiura, S M

    2009-12-01

    Several factors that influence the evolution of the unusual head morphology of hammerhead sharks (family Sphyrnidae) are proposed but few are empirically tested. In this study we tested the 'enhanced binocular field' hypothesis (that proposes enhanced frontal binocularity) by comparison of the visual fields of three hammerhead species: the bonnethead shark, Sphyrna tiburo, the scalloped hammerhead shark, Sphyrna lewini, and the winghead shark, Eusphyra blochii, with that of two carcharhinid species: the lemon shark, Negaprion brevirostris, and the blacknose shark, Carcharhinus acronotus. Additionally, eye rotation and head yaw were quantified to determine if species compensate for large blind areas anterior to the head. The winghead shark possessed the largest anterior binocular overlap (48 deg.) and was nearly four times larger than that of the lemon (10 deg.) and blacknose (11 deg.) sharks. The binocular overlap in the scalloped hammerhead sharks (34 deg.) was greater than the bonnethead sharks (13 deg.) and carcharhinid species; however, the bonnethead shark did not differ from the carcharhinids. These results indicate that binocular overlap has increased with lateral head expansion in hammerhead sharks. The hammerhead species did not demonstrate greater eye rotation in the anterior or posterior direction. However, both the scalloped hammerhead and bonnethead sharks exhibited greater head yaw during swimming (16.9 deg. and 15.6 deg., respectively) than the lemon (15.1 deg.) and blacknose (15.0 deg.) sharks, indicating a behavioral compensation for the anterior blind area. This study illustrates the larger binocular overlap in hammerhead species relative to their carcharhinid sister taxa and is consistent with the 'enhanced binocular field' hypothesis.

  4. Hooking mortality of scalloped hammerhead Sphyrna lewini and great hammerhead Sphyrna mokarran sharks caught on bottom longlines

    National Research Council Canada - National Science Library

    Gulak, SJB; de Ron Santiago, AJ; Carlson, JK

    2015-01-01

    The scalloped hammerhead Sphyrna lewini and the great hammerhead S. mokarran are typically caught as bycatch in a variety of fisheries and are listed as globally Endangered by the International Union for the Conservation of Nature...

  5. Hooking mortality of scalloped hammerhead Sphyrna lewini and ...

    African Journals Online (AJOL)

    When these data are considered for potential management strategies to reduce the mortality of hammerhead sharks, a limitation on gear soak time would probably improve hammerhead shark survivorship. However, it may ... hammerheads. Keywords: bycatch, hook timer, logistic regression, soak time, time on the hook ...

  6. Investigating single and multiple species fisheries management: stock status evaluation of hammerhead (Sphyrna spp.) sharks in the western North Atlantic Ocean and Gulf of Mexico.

    OpenAIRE

    Hayes, Christopher Glenn

    2007-01-01

    Three hammerhead sharks (Sphyrna spp.) are currently managed as part of the large coastal shark complex in the United States. Including multiple species in an assessment ignores the different stock dynamics of each individual species within the complex due to different life histories. This study completed individual assessments of scalloped (S. lewini), great (S. mokarran), and smooth (S. zygaena) hammerhead sharks in the U.S. Atlantic Ocean and Gulf of Mexico. Combined data for all three ...

  7. Variability in multiple paternity rates for grey reef sharks (Carcharhinus amblyrhynchos) and scalloped hammerheads (Sphyrna lewini).

    Science.gov (United States)

    Green, M E; Appleyard, S A; White, W; Tracey, S; Ovenden, J

    2017-05-08

    This study assessed the presence and prevalence of multiple paternity (MP) in litters of grey reef sharks (Carcharhinus amblyrhynchos) and scalloped hammerheads (Sphyrna lewini) opportunistically caught in Papua New Guinea (PNG). Litter size between species were significantly different with an average of 3.3 pups for grey reef sharks and 17.2 pups for scalloped hammerhead. Using 14 and 10 microsatellite loci respectively, we identified MP in 66% of grey reef sharks (4 out of 6 litters) and 100% MP in scalloped hammerheads (5 litters). We found high paternal skew (the uneven contribution of sires per litter) and a positive correlation between female adult size and litter size in scalloped hammerheads but not in grey reef sharks. Differences in the frequency of MP between species and the identification of paternal skew may be linked with mating strategies and post-copulatory mechanisms. Multiple paternity is thought to benefit populations by enhancing genetic diversity therefore increasing the population's genetic resilience to extrinsic pressures. The identification of MP in two shark species reported here, further elucidates the complex breeding strategies elasmobranchs undertake.

  8. Virgin birth in a hammerhead shark

    OpenAIRE

    Chapman, D. D.; Shivji, M.S.; Louis, E.; Sommer, J; Fletcher, Hugh; PRODOHL Paulo

    2007-01-01

    Parthenogenesis has been documented in all major jawed vertebrate lineages except mammals and cartilaginous fishes (class Chondrichthyes: sharks, batoids and chimeras). Reports of captive female sharks giving birth despite being held in the extended absence of males have generally been ascribed to prior matings coupled with long-term sperm storage by the females. Here, we provide the first genetic evidence for chondrichthyan parthenogenesis, involving a hammerhead shark (Sphyrna tiburo). This...

  9. Mechanistic Debris Generated by Twister Ribozymes.

    Science.gov (United States)

    Breaker, Ronald R

    2017-04-21

    Twister RNAs represent a recently discovered class of natural ribozymes that promote rapid cleaving of RNA backbones. Although an abundance of theoretical, biochemical, and structural data exist for several members of the twister class, disagreements about the architecture and mechanism of its active site have emerged. Historically, such storms regarding mechanistic details typically occur soon after each new self-cleaving ribozyme class is reported, but paths forward exist to quickly reach calmer conditions.

  10. Virgin birth in a hammerhead shark.

    Science.gov (United States)

    Chapman, Demian D; Shivji, Mahmood S; Louis, Ed; Sommer, Julie; Fletcher, Hugh; Prodöhl, Paulo A

    2007-08-22

    Parthenogenesis has been documented in all major jawed vertebrate lineages except mammals and cartilaginous fishes (class Chondrichthyes: sharks, batoids and chimeras). Reports of captive female sharks giving birth despite being held in the extended absence of males have generally been ascribed to prior matings coupled with long-term sperm storage by the females. Here, we provide the first genetic evidence for chondrichthyan parthenogenesis, involving a hammerhead shark (Sphyrna tiburo). This finding also broadens the known occurrence of a specific type of asexual development (automictic parthenogenesis) among vertebrates, extending recently raised concerns about the potential negative effect of this type of facultative parthenogenesis on the genetic diversity of threatened vertebrate species.

  11. Structural basis for Diels-Alder ribozyme-catalyzed carbon-carbon bond formation

    Science.gov (United States)

    Serganov, Alexander; Keiper, Sonja; Malinina, Lucy; Tereshko, Valentina; Skripkin, Eugene; Höbartner, Claudia; Polonskaia, Anna; Phan, Anh Tuân; Wombacher, Richard; Micura, Ronald; Dauter, Zbigniew; Jäschke, Andres; Patel, Dinshaw J

    2015-01-01

    The majority of structural efforts addressing RNA’s catalytic function have focused on natural ribozymes, which catalyze phosphodiester transfer reactions. By contrast, little is known about how RNA catalyzes other types of chemical reactions. We report here the crystal structures of a ribozyme that catalyzes enantioselective carbon-carbon bond formation by the Diels-Alder reaction in the unbound state and in complex with a reaction product. The RNA adopts a λ-shaped nested pseudoknot architecture whose preformed hydrophobic pocket is precisely complementary in shape to the reaction product. RNA folding and product binding are dictated by extensive stacking and hydrogen bonding, whereas stereoselection is governed by the shape of the catalytic pocket. Catalysis is apparently achieved by a combination of proximity, complementarity and electronic effects. We observe structural parallels in the independently evolved catalytic pocket architectures for ribozyme- and antibody-catalyzed Diels-Alder carbon-carbon bond-forming reactions. PMID:15723077

  12. Response of the hammerhead shark olfactory epithelium to amino acid stimuli.

    Science.gov (United States)

    Tricas, Timothy C; Kajiura, Stephen M; Summers, Adam P

    2009-10-01

    Sharks and rays are highly sensitive to chemical stimuli in their natural environment but several hypotheses predict that hammerhead sharks, with their expanded head and enlarged olfactory epithelium, have particularly acute olfactory systems. We used the electro-olfactogram (EOG) technique to compare the relative response of the scalloped hammerhead shark (Sphyrna lewini) olfactory epithelium to 20 proteinogenic amino acids and determine the sensitivity for 6 amino acids. At micromolar concentrations, cysteine evoked the greatest EOG response which was approximately twice as large as that of alanine. The weakest response was obtained for proline followed by aspartic acid and isoleucine. The olfactory epithelium showed adaptation to sequential stimulation, and recovery was related to the inter-stimulus time period. Estimated EOG response thresholds were in the sub-nanomolar range for both alanine (9.2 x 10(-11) M) and cysteine (8.4 x 10(-10) M) and in the micromolar range for proline and serine. These thresholds from 10(-10) to 10(-6) M for the scalloped hammerhead shark are comparable or lower than those reported for other teleost and elasmobranch species. Future work should focus on binary and more complex compounds to test for competition and cross-adaptation for different classes of peripheral receptors, and their responses to molecules found in biologically relevant stimuli.

  13. Crossing lines: a multidisciplinary framework for assessing connectivity of hammerhead sharks across jurisdictional boundaries

    Science.gov (United States)

    Chin, A.; Simpfendorfer, C. A.; White, W. T.; Johnson, G. J.; McAuley, R. B.; Heupel, M. R.

    2017-04-01

    Conservation and management of migratory species can be complex and challenging. International agreements such as the Convention on Migratory Species (CMS) provide policy frameworks, but assessments and management can be hampered by lack of data and tractable mechanisms to integrate disparate datasets. An assessment of scalloped (Sphyrna lewini) and great (Sphyrna mokarran) hammerhead population structure and connectivity across northern Australia, Indonesia and Papua New Guinea (PNG) was conducted to inform management responses to CMS and Convention on International Trade in Endangered Species listings of these species. An Integrated Assessment Framework (IAF) was devised to systematically incorporate data across jurisdictions and create a regional synopsis, and amalgamated a suite of data from the Australasian region. Scalloped hammerhead populations are segregated by sex and size, with Australian populations dominated by juveniles and small adult males, while Indonesian and PNG populations included large adult females. The IAF process introduced genetic and tagging data to produce conceptual models of stock structure and movement. Several hypotheses were produced to explain stock structure and movement patterns, but more data are needed to identify the most likely hypothesis. This study demonstrates a process for assessing migratory species connectivity and highlights priority areas for hammerhead management and research.

  14. Crossing lines: a multidisciplinary framework for assessing connectivity of hammerhead sharks across jurisdictional boundaries.

    Science.gov (United States)

    Chin, A; Simpfendorfer, C A; White, W T; Johnson, G J; McAuley, R B; Heupel, M R

    2017-04-21

    Conservation and management of migratory species can be complex and challenging. International agreements such as the Convention on Migratory Species (CMS) provide policy frameworks, but assessments and management can be hampered by lack of data and tractable mechanisms to integrate disparate datasets. An assessment of scalloped (Sphyrna lewini) and great (Sphyrna mokarran) hammerhead population structure and connectivity across northern Australia, Indonesia and Papua New Guinea (PNG) was conducted to inform management responses to CMS and Convention on International Trade in Endangered Species listings of these species. An Integrated Assessment Framework (IAF) was devised to systematically incorporate data across jurisdictions and create a regional synopsis, and amalgamated a suite of data from the Australasian region. Scalloped hammerhead populations are segregated by sex and size, with Australian populations dominated by juveniles and small adult males, while Indonesian and PNG populations included large adult females. The IAF process introduced genetic and tagging data to produce conceptual models of stock structure and movement. Several hypotheses were produced to explain stock structure and movement patterns, but more data are needed to identify the most likely hypothesis. This study demonstrates a process for assessing migratory species connectivity and highlights priority areas for hammerhead management and research.

  15. Diet of scalloped hammerhead shark in eastern Gulf of Mexico

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Juvenile scalloped hammerhead sharks, Sphyrna lewini, were collected in northwest Florida to examine foraging ecology, bioenergetics, and trophic level (30-60 cm FL...

  16. Chemical fidelity of an RNA polymerase ribozyme

    DEFF Research Database (Denmark)

    Attwater, J.; Tagami, S.; Kimoto, M.

    2013-01-01

    The emergence of catalytically active RNA enzymes (ribozymes) is widely believed to have been an important transition in the origin of life. In the context of a likely heterogeneous chemical environment, substrate specificity and selectivity of these primordial enzymes would have been critical...... for function. Here we have explored the chemical fidelity, i.e. substrate selectivity and specificity for both single and multiple catalytic steps of the Z RNA polymerase ribozyme-a modern day analogue of the primordial RNA replicase. Using a wide range of nucleotide analogues and ionic conditions, we observe...

  17. Reaction pathway of the trans-acting hepatitis delta virus ribozyme: a conformational change accompanies catalysis.

    Science.gov (United States)

    Pereira, Miguel J B; Harris, Dinari A; Rueda, David; Walter, Nils G

    2002-01-22

    The hepatitis delta virus (HDV), an infectious human pathogen and satellite of hepatitis B virus, leads to intensified disease symptoms, including progression to liver cirrhosis. Both the circular RNA genome of HDV and its complementary antigenome contain the same cis-cleaving catalytic RNA motif that plays a crucial role in virus replication. Previously, the high-resolution crystal structure of the product form of a cis-acting genomic HDV ribozyme has been determined, while a trans-acting version of the ribozyme was used to dissect the cleavage reaction pathway. Using fluorescence resonance energy transfer (FRET) on a synthetic trans-cleaving form of the ribozyme, we are able to directly observe substrate binding (at a rate constant k(on) of 7.8 x 10(6) M(-1) min(-1) at pH 7.5, 11 mM MgCl(2), and 25 degrees C) and dissociation (at 0.34 min(-1)). Steady-state and time-resolved FRET experiments in solution and in nondenaturing gels reveal that the substrate (precursor) complex is slightly more compact (by approximately 3 A) than the free ribozyme, yet becomes significantly extended (by approximately 15 A) upon cleavage and product complex formation. We also find that trans cleavage is characterized by a high transition-state entropy (-26 eu). We propose that the significant global conformational change that we observe between the precursor and product structures occurs on the reaction trajectory into a constrained product complex-like transition state. Our observations may present the structural basis of the recently described utilization of intrinsic substrate binding energy to the overall catalytic rate enhancement by the trans-acting HDV ribozyme.

  18. Inhibition of gene expression in human cells using RNase P-derived ribozymes and external guide sequences

    OpenAIRE

    Kim, Kihoon; Liu, Fenyong

    2007-01-01

    Ribonuclease P (RNase P) complexed with an external guide sequence (EGS) represents a novel nucleic acid-based gene interference approach to modulate gene expression. This enzyme is a ribonucleoprotein complex for tRNA processing. In E. coli, RNase P contains a catalytic RNA subunit (M1 ribozyme) and a protein subunit (C5 cofactor). EGSs, which are RNAs derived from natural tRNAs, bind to a target mRNA and render the mRNA susceptible to hydrolysis by RNase P and M1 ribozyme. When covalently l...

  19. Assembly and activation of a kinase ribozyme.

    Science.gov (United States)

    Burke, Donald H; Rhee, Steven S

    2010-12-01

    RNA activities can be regulated by modulating the relative energies of all conformations in a folding landscape; however, it is often unknown precisely how peripheral elements perturb the overall landscape in the absence of discrete alternative folds (inactive ensemble). This work explores the effects of sequence and secondary structure in governing kinase ribozyme activity. Kin.46 catalyzes thiophosphoryl transfer from ATPγS onto the 5' hydroxyl of polynucleotide substrates, and is regulated 10,000-fold by annealing an effector oligonucleotide to form activator helix P4. Transfer kinetics for an extensive series of ribozyme variants identified several dispensable internal single-stranded segments, in addition to a potential pseudoknot at the active site between segments J1/4 and J3/2 that is partially supported by compensatory rescue. Standard allosteric mechanisms were ruled out, such as formation of discrete repressive structures or docking P4 into the rest of the ribozyme via backbone 2' hydroxyls. Instead, P4 serves both to complete an important structural element (100-fold contribution to the reaction relative to a P4-deleted variant) and to mitigate nonspecific, inhibitory effects of the single-stranded tail (an additional 100-fold contribution to the apparent rate constant, k(obs)). Thermodynamic activation parameters ΔH(‡) and ΔS(‡), calculated from the temperature dependence of k(obs), varied with tail length and sequence. Inhibitory effects of the unpaired tail are largely enthalpic for short tails and are both enthalpic and entropic for longer tails. These results refine the structural view of this kinase ribozyme and highlight the importance of nonspecific ensemble effects in conformational regulation by peripheral elements.

  20. High-Throughput Mutational Analysis of a Twister Ribozyme.

    Science.gov (United States)

    Kobori, Shungo; Yokobayashi, Yohei

    2016-08-22

    Recent discoveries of new classes of self-cleaving ribozymes in diverse organisms have triggered renewed interest in the chemistry and biology of ribozymes. Functional analysis and engineering of ribozymes often involve performing biochemical assays on multiple ribozyme mutants. However, because each ribozyme mutant must be individually prepared and assayed, the number and variety of mutants that can be studied are severely limited. All of the single and double mutants of a twister ribozyme (a total of 10 296 mutants) were generated and assayed for their self-cleaving activity by exploiting deep sequencing to count the numbers of cleaved and uncleaved sequences for every mutant. Interestingly, we found that the ribozyme is highly robust against mutations such that 71 % and 30 % of all single and double mutants, respectively, retain detectable activity under the assay conditions. It was also observed that the structural elements that comprise the ribozyme exhibit distinct sensitivity to mutations. © 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

  1. Structural and Biochemical Properties of Novel Self-Cleaving Ribozymes.

    Science.gov (United States)

    Lee, Ki-Young; Lee, Bong-Jin

    2017-04-24

    Fourteen well-defined ribozyme classes have been identified to date, among which nine are site-specific self-cleaving ribozymes. Very recently, small self-cleaving ribozymes have attracted renewed interest in their structure, biochemistry, and biological function since the discovery, during the last three years, of four novel ribozymes, termed twister, twister sister, pistol, and hatchet. In this review, we mainly address the structure, biochemistry, and catalytic mechanism of the novel ribozymes. They are characterized by distinct active site architectures and divergent, but similar, biochemical properties. The cleavage activities of the ribozymes are highly dependent upon divalent cations, pH, and base-specific mutations, which can cause changes in the nucleotide arrangement and/or electrostatic potential around the cleavage site. It is most likely that a guanine and adenine in close proximity of the cleavage site are involved in general acid-base catalysis. In addition, metal ions appear to play a structural rather than catalytic role although some of their crystal structures have shown a direct metal ion coordination to a non-bridging phosphate oxygen at the cleavage site. Collectively, the structural and biochemical data of the four newest ribozymes could contribute to advance our mechanistic understanding of how self-cleaving ribozymes accomplish their efficient site-specific RNA cleavages.

  2. Helium ion beam induced growth of hammerhead AFM probes

    NARCIS (Netherlands)

    Nanda, G.; Van Veldhoven, E.; Maas, D.; Sadeghian, H.; Alkemade, P.F.A.

    2015-01-01

    The authors report the direct-write growth of hammerhead atomic force microscope(AFM) probes by He+beam induced deposition of platinum-carbon. In order to grow a thin nanoneedle on top of a conventional AFM probe, the authors move a focused He+beam during exposure to a PtC precursor gas. In the

  3. Helium ion beam induced growth of hammerhead AFM probes

    NARCIS (Netherlands)

    Nanda, G.; Veldhoven, E. van; Maas, D.J.; Sadeghian Marnani, H.; Alkemade, P.F.A.

    2015-01-01

    The authors report the direct-write growth of hammerhead atomic force microscope (AFM) probes by He+ beam induced deposition of platinum-carbon. In order to grow a thin nanoneedle on top of a conventional AFM probe, the authors move a focused He+ beam during exposure to a PtC precursor gas. In the

  4. Molecular modelling of the GIR1 branching ribozyme gives new insight into evolution of structurally related ribozymes

    DEFF Research Database (Denmark)

    Beckert, Bertrand Dominique; Nielsen, Henrik; Einvik, Christer

    2008-01-01

    related to group I ribozymes raising the question about how two closely related ribozymes can carry out very different reactions. Modelling of GIR1 based on new biochemical and mutational data shows an extended substrate domain containing a GoU pair distinct from the nucleophilic residue that dock onto...

  5. Inhibition of gene expression in human cells using RNase P-derived ribozymes and external guide sequences.

    Science.gov (United States)

    Kim, Kihoon; Liu, Fenyong

    2007-01-01

    Ribonuclease P (RNase P) complexed with an external guide sequence (EGS) represents a novel nucleic acid-based gene interference approach to modulate gene expression. This enzyme is a ribonucleoprotein complex for tRNA processing. In Escherichia coli, RNase P contains a catalytic RNA subunit (M1 ribozyme) and a protein subunit (C5 cofactor). EGSs, which are RNAs derived from natural tRNAs, bind to a target mRNA and render the mRNA susceptible to hydrolysis by RNase P and M1 ribozyme. When covalently linked with a guide sequence, M1 can be engineered into a sequence-specific endonuclease, M1GS ribozyme, which cleaves any target RNAs that base pair with the guide sequence. Studies have demonstrated efficient cleavage of mRNAs by M1GS and RNase P complexed with EGSs in vitro. Moreover, highly active M1GS and EGSs were successfully engineered using in vitro selection procedures. EGSs and M1GS ribozymes are effective in blocking gene expression in both bacteria and human cells, and exhibit promising activity for antimicrobial, antiviral, and anticancer applications. In this review, we highlight some recent results using the RNase P-based technology, and offer new insights into the future of using EGS and M1GS RNA as tools for basic research and as gene-targeting agents for clinical applications.

  6. Regional variation in undulatory kinematics of two hammerhead species: the bonnethead (Sphyrna tiburo) and the scalloped hammerhead (Sphyrna lewini).

    Science.gov (United States)

    Hoffmann, Sarah L; Warren, Steven M; Porter, Marianne E

    2017-09-15

    Hammerhead sharks (Sphyrnidae) exhibit a large amount of morphological variation within the family, making them the focus of many studies. The size of the laterally expanded head, or cephalofoil, is inversely correlated with pectoral fin area. The inverse relationship between cephalofoil and pectoral fin size in this family suggests that they might serve a complementary role in lift generation. The cephalofoil is also hypothesized to increase olfaction, electroreception and vision; however, little is known about how morphological variation impacts post-cranial swimming kinematics. Previous studies demonstrate that the bonnethead and scalloped hammerhead have significantly different yaw amplitude, and we hypothesized that these species utilize varied frequency and amplitude of undulation along the body. We analyzed video of free-swimming sharks to examine kinematics and 2D morphological variables of the bonnethead and scalloped hammerhead. We also examined the second moment of area along the length of the body and over a size range of animals to determine whether there were shape differences along the body of these species and whether those changed over ontogeny. We found that both species swim with the same standardized velocity and Strouhal number, but there was no correlation between two-dimensional morphology and swimming kinematics. However, the bonnethead has a dorso-ventrally compressed anterior trunk and undulates with greater amplitude, whereas the scalloped hammerhead has a laterally compressed anterior trunk and undulates with lower amplitude. We propose that differences in cross-sectional trunk morphology account for interspecific differences in undulatory amplitude. We also found that for both species, undulatory frequency is significantly greater in the anterior body compared with all other body regions. We hypothesize that the bonnethead and scalloped hammerhead swim with a double oscillation system. © 2017. Published by The Company of Biologists Ltd.

  7. Spliceozymes: ribozymes that remove introns from pre-mRNAs in trans.

    Directory of Open Access Journals (Sweden)

    Zhaleh N Amini

    Full Text Available Group I introns are pre-mRNA introns that do not require the spliceosome for their removal. Instead, they fold into complex three-dimensional structures and catalyze two transesterification reactions, thereby excising themselves and joining the flanking exons. These catalytic RNAs (ribozymes have been modified previously to work in trans, whereby the ribozymes can recognize a splice site on a substrate RNA and replace the 5'- or 3'-portion of the substrate. Here we describe a new variant of the group I intron ribozyme from Tetrahymena that recognizes two splice sites on a substrate RNA, removes the intron sequences between the splice sites, and joins the flanking exons, analogous to the action of the spliceosome. This 'group I spliceozyme' functions in vitro and in vivo, and it is able to mediate a growth phenotype in E. coli cells. The intron sequences of the target pre-mRNAs are constrained near the splice sites but can carry a wide range of sequences in their interior. Because the splice site recognition sequences can be adjusted to different splice sites, the spliceozyme may have the potential for wide applications as tool in research and therapy.

  8. Thermodynamics and kinetics of RNA tertiary structure formation in the junctionless hairpin ribozyme.

    Science.gov (United States)

    White, Neil A; Hoogstraten, Charles G

    2017-09-01

    The hairpin ribozyme consists of two RNA internal loops that interact to form the catalytically active structure. This docking transition is a rare example of intermolecular formation of RNA tertiary structure without coupling to helix annealing. We have used temperature-dependent surface plasmon resonance (SPR) to characterize the thermodynamics and kinetics of RNA tertiary structure formation for the junctionless form of the ribozyme, in which loops A and B reside on separate molecules. We find docking to be strongly enthalpy-driven and to be accompanied by substantial activation barriers for association and dissociation, consistent with the structural reorganization of both internal loops upon complex formation. Comparisons with the parallel analysis of a ribozyme variant carrying a 2'-O-methyl modification at the self-cleavage site and with published data in other systems reveal a surprising diversity of thermodynamic signatures, emphasizing the delicate balance of contributions to the free energy of formation of RNA tertiary structure. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. The mitochondrial genome of the hammerhead Sphyrna zygaena.

    Science.gov (United States)

    Bolaño-Martínez, Nataly; Bayona-Vasquez, Natalia; Uribe-Alcocer, Manuel; Díaz-Jaimes, Píndaro

    2016-05-01

    The hammerhead shark (Sphyrna zygaena) is listed as a "Vulnerable" species for the International Union for Conservation of Nature (IUCN). Here we report the complete sequence for the mitochondrial genome of the hammerhead shark of a specimen collected from the eastern Pacific Ocean. The genome structure is quite similar to other reported mtDNA shark species. It has a total length of 16,731 base pairs (bp); the base composition was A (31.54%), T (30.23%) C (25.03%) and G: 13.20, contains 13 protein-coding genes, 2 rRNA genes; 21 tRNA genes. In addition, most of the starting (ATG) and ending codons (TAA) for the mtDNA gene regions were registered.

  10. Functional morphology of the nasal region of a hammerhead shark.

    Science.gov (United States)

    Abel, Richard L; Maclaine, James S; Cotton, Ross; Xuan, Viet Bui; Nickels, Timothy B; Clark, Thomas H; Wang, Zhijin; Cox, Jonathan P L

    2010-04-01

    We describe several novel morphological features in the nasal region of the hammerhead shark Sphyrna tudes. Unlike the open, rounded incurrent nostril of non-hammerhead shark species, the incurrent nostril of S. tudes is a thin keyhole-like aperture. We discovered a groove running anterior and parallel to the incurrent nostril. This groove, dubbed the minor nasal groove to distinguish it from the larger, previously described, (major) nasal groove, is common to all eight hammerhead species. Using life-sized plastic models generated at 200 microm resolution from an X-ray scan, we also investigated flow in the nasal region. Even modest oncoming flow speeds stimulate extensive, but not complete, circulation within the model olfactory chamber, with flow passing through the two main olfactory channels. Flow crossed from one channel to another via a gap in the olfactory array, sometimes guided by the interlamellar channels. Major and minor nasal grooves, as well as directing flow into the olfactory chamber, can, in conjunction with the nasal bridge separating incurrent and excurrent nostrils, limit flow passing into the olfactory chamber, possibly to protect the delicate nasal structures. This is the first simulation of internal flow within the olfactory chamber of a shark.

  11. Electroreception in juvenile scalloped hammerhead and sandbar sharks.

    Science.gov (United States)

    Kajiura, Stephen M; Holland, Kim N

    2002-12-01

    The unique head morphology of sphyrnid sharks might have evolved to enhance electrosensory capabilities. The 'enhanced electroreception' hypothesis was tested by comparing the behavioral responses of similarly sized carcharhinid and sphyrnid sharks to prey-simulating electric stimuli. Juvenile scalloped hammerhead sharks Sphyrna lewini and sandbar sharks Carcharhinus plumbeus oriented to dipole electric fields from the same maximum distance (approximately 30 cm) and thus demonstrated comparable behavioral-response thresholds (hammerheads typically demonstrated a pivot orientation in which the edge of the cephalofoil closest to the dipole remained stationary while the shark bent its trunk to orient to the center of the dipole. By contrast, sandbars swam in a broader arc towards the center of the dipole. The different orientation patterns are attributed to the hydrodynamic properties of the cephalofoil, which enables the hammerheads to execute sharp turns at high speed. The greater trunk width of the sandbar sharks prevented them from demonstrating the same degree of flexibility. Therefore, although the sphyrnid head morphology does not appear to confer a greater sensitivity to prey-simulating dipole electric fields, it does provide (1). a greater lateral search area, which may increase the probability of prey encounter, and (2). enhanced maneuverability, which may aid in prey capture.

  12. Twister ribozymes as highly versatile expression platforms for artificial riboswitches.

    Science.gov (United States)

    Felletti, Michele; Stifel, Julia; Wurmthaler, Lena A; Geiger, Sophie; Hartig, Jörg S

    2016-09-27

    The utilization of ribozyme-based synthetic switches in biotechnology has many advantages such as an increased robustness due to in cis regulation, small coding space and a high degree of modularity. The report of small endonucleolytic twister ribozymes provides new opportunities for the development of advanced tools for engineering synthetic genetic switches. Here we show that the twister ribozyme is distinguished as an outstandingly flexible expression platform, which in conjugation with three different aptamer domains, enables the construction of many different one- and two-input regulators of gene expression in both bacteria and yeast. Besides important implications in biotechnology and synthetic biology, the observed versatility in artificial genetic control set-ups hints at possible natural roles of this widespread ribozyme class.

  13. Ribozyme genes protecting transgenic melon plants against potyviruses

    National Research Council Canada - National Science Library

    Huttner, E; Tucker, W; Vermeulen, A; Ignart, F; Sawyer, B; Birch, R

    2001-01-01

    Potyviruses are the most important viral pathogens of crops worldwide. Under a contract with Gene Shears Pty Limited, we are using ribozyme genes to protect melon plants against two potyviruses: WMV2 and ZYMV...

  14. 76 FR 23794 - Stock Status Determination for Atlantic Highly Migratory Scalloped Hammerhead Shark

    Science.gov (United States)

    2011-04-28

    ... Scalloped Hammerhead Shark AGENCY: National Marine Fisheries Service (NMFS), National Oceanic and... an Atlantic highly migratory species (HMS) scalloped hammerhead shark, and the stock is overfished... sharks in U.S. waters. Based on this paper, in 2005, the population was estimated to be at 45 percent of...

  15. Speciation of a group I intron into a lariat capping ribozyme

    DEFF Research Database (Denmark)

    Meyer, Mélanie; Nielsen, Henrik; Oliéric, Vincent

    2014-01-01

    The lariat-capping (LC) ribozyme is a natural ribozyme isolated from eukaryotic microorganisms. Despite apparent structural similarity to group I introns, the LC ribozyme catalyzes cleavage by a 2',5' branching reaction, leaving the 3' product with a 3-nt lariat cap that functionally substitutes ...

  16. Modulation of Group I Ribozyme Activity by Cationic Porphyrins

    Science.gov (United States)

    Matsumura, Shigeyoshi; Ito, Tatsunobu; Tanaka, Takahiro; Furuta, Hiroyuki; Ikawa, Yoshiya

    2015-01-01

    The effects of cationic porphyrins on the catalytic activities of four group I ribozymes were investigated. A cationic porphyrin possessing four pyridinium moieties (pPyP) inhibited two group IC3 ribozymes (Syn Rz and Azo Rz) and a group IC1 ribozyme (Tet Rz). In the case of a group IA2 ribozyme (Td Rz), however, pPyP served not only as an inhibitor but also as an activator, and the effects of pPyP were dependent on its concentration. To analyze the structural and electronic factors determining the effects of pPyP on group I ribozymes, three cationic porphyrins (pPyNCP, pPyF4P, and TMPyP) were also examined. As interactions between small organic molecules and nucleic acids are attractive and important issues in biochemistry and biotechnology, this study contributes to the development of porphyrin-based molecules that can modulate functions of structured RNA molecules. PMID:25811638

  17. Modulation of Group I Ribozyme Activity by Cationic Porphyrins

    Directory of Open Access Journals (Sweden)

    Shigeyoshi Matsumura

    2015-03-01

    Full Text Available The effects of cationic porphyrins on the catalytic activities of four group I ribozymes were investigated. A cationic porphyrin possessing four pyridinium moieties (pPyP inhibited two group IC3 ribozymes (Syn Rz and Azo Rz and a group IC1 ribozyme (Tet Rz. In the case of a group IA2 ribozyme (Td Rz, however, pPyP served not only as an inhibitor but also as an activator, and the effects of pPyP were dependent on its concentration. To analyze the structural and electronic factors determining the effects of pPyP on group I ribozymes, three cationic porphyrins (pPyNCP, pPyF4P, and TMPyP were also examined. As interactions between small organic molecules and nucleic acids are attractive and important issues in biochemistry and biotechnology, this study contributes to the development of porphyrin-based molecules that can modulate functions of structured RNA molecules.

  18. Multifrequency Pulsed EPR Studies of Biologically Relevant Manganese(II) Complexes.

    Science.gov (United States)

    Stich, T A; Lahiri, S; Yeagle, G; Dicus, M; Brynda, M; Gunn, A; Aznar, C; Derose, V J; Britt, R D

    2007-03-01

    Electron paramagnetic resonance studies at multiple frequencies (MF EPR) can provide detailed electronic structure descriptions of unpaired electrons in organic radicals, inorganic complexes, and metalloenzymes. Analysis of these properties aids in the assignment of the chemical environment surrounding the paramagnet and provides mechanistic insight into the chemical reactions in which these systems take part. Herein, we present results from pulsed EPR studies performed at three different frequencies (9, 31, and 130 GHz) on [Mn(II)(H(2)O)(6)](2+), Mn(II) adducts with the nucleotides ATP and GMP, and the Mn(II)-bound form of the hammerhead ribozyme (MnHH). Through line shape analysis and interpretation of the zero-field splitting values derived from successful simulations of the corresponding continuous-wave and field-swept echo-detected spectra, these data are used to exemplify the ability of the MF EPR approach in distinguishing the nature of the first ligand sphere. A survey of recent results from pulsed EPR, as well as pulsed electron-nuclear double resonance and electron spin echo envelope modulation spectroscopic studies applied to Mn(II)-dependent systems, is also presented.

  19. Kinetic partitioning mechanism of HDV ribozyme folding

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Jiawen; Gong, Sha; Wang, Yujie; Zhang, Wenbing, E-mail: wbzhang@whu.edu.cn [Department of Physics, Wuhan University, Wuhan, Hubei 430072 (China)

    2014-01-14

    RNA folding kinetics is directly tied to RNA biological functions. We introduce here a new approach for predicting the folding kinetics of RNA secondary structure with pseudoknots. This approach is based on our previous established helix-based method for predicting the folding kinetics of RNA secondary structure. In this approach, the transition rates for an elementary step: (1) formation, (2) disruption of a helix stem, and (3) helix formation with concomitant partial melting of an incompatible helix, are calculated with the free energy landscape. The folding kinetics of the Hepatitis delta virus (HDV) ribozyme and the mutated sequences are studied with this method. The folding pathways are identified by recursive searching the states with high net flux-in(out) population starting from the native state. The theory results are in good agreement with that of the experiments. The results indicate that the bi-phasic folding kinetics for the wt HDV sequence is ascribed to the kinetic partitioning mechanism: Part of the population will quickly fold to the native state along the fast pathway, while another part of the population will fold along the slow pathway, in which the population is trapped in a non-native state. Single mutation not only changes the folding rate but also the folding pathway.

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

    Science.gov (United States)

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

    2016-01-01

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

  1. Scalloped hammerhead shark Sphyrna lewini, utilizes deep-water, hypoxic zone in the Gulf of California.

    Science.gov (United States)

    Jorgensen, S J; Klimley, A P; Muhlia-Melo, A F

    2009-05-01

    A hammerhead shark Sphyrna lewini tracked for 74 days revealed an expansion of the range of vertical distribution for the species to include the extreme hypoxic environment of the oxygen minimum layer in the Gulf of California.

  2. Maneuvering in juvenile carcharhinid and sphyrnid sharks: the role of the hammerhead shark cephalofoil.

    Science.gov (United States)

    Kajiura, Stephen M; Forni, Jesica B; Summers, Adam P

    2003-01-01

    The peculiar head morphology of hammerhead sharks has spawned a variety of untested functional hypotheses. One of the most intuitively appealing ideas is that the anterior foil acts, as in canard-winged aircraft, to increase maneuverability. We tested this hypothesis by determining whether juveniles of two hammerhead species (Sphyrna tiburo and S. lewini) turn more sharply, more often, and with greater velocity than a juvenile carcharhinid shark (Carcharhinus plumbeus). Although the hammerheads were more maneuverable, further investigation revealed that they do not roll their body during turns, suggesting that the cephalofoil does not act as a steering wing. We also show that hammerhead sharks demonstrate greater lateral flexure in a turn than carcharhinids, and that this flexibility may be due to cross sectional shape rather than number of vertebrae.

  3. Reproductive biology of the scalloped Hammerhead shark Sphyrna lewini (Chondrichthyes: Sphyrnidae) off southwest Mexico

    OpenAIRE

    Bejarano-Álvarez, Marcela; Galván Magaña, Felipe; Ochoa Báez, Rosa Isabel

    2011-01-01

    The scalloped hammerhead shark Sphyrna lewini is the most important species in the artisanal shark fishery in the Gulf of Tehuantepec, Mexico. The knowledge about their reproductive biology in the area is nonexistent, despite their being listed worldwide as endangered by the IUCN. To determine the basic biology of reproduction in this shark would give important data to establish management or conservation plans for this species in Mexico. Samples were collected of 991 hammerhead sharks (342 f...

  4. Metals induce transient folding and activation of the twister ribozyme.

    Science.gov (United States)

    Panja, Subrata; Hua, Boyang; Zegarra, Diego; Ha, Taekjip; Woodson, Sarah A

    2017-10-01

    Twister is a small ribozyme present in almost all kingdoms of life that rapidly self-cleaves in variety of divalent metal ions. We used activity assays, bulk FRET and single-molecule FRET (smFRET) to understand how different metal ions promote folding and self-cleavage of the Oryza sativa twister ribozyme. Although most ribozymes require additional Mg2+ for catalysis, twister inverts this expectation, requiring 20-30 times less Mg2+ to self-cleave than to fold. Transition metals such as Co2+, Ni2+ and Zn2+ activate twister more efficiently than Mg2+ ions. Although twister is fully active in ≤ 0.5 mM MgCl2, smFRET experiments showed that the ribozyme visits the folded state infrequently under these conditions. Comparison of folding and self-cleavage rates indicates that most folding events lead to catalysis, which correlates with metal bond strength. Thus, the robust activity of twister reports on transient metal ion binding under physiological conditions.

  5. Constructional morphology within the head of hammerhead sharks (sphyrnidae).

    Science.gov (United States)

    Mara, Kyle R; Motta, Philip J; Martin, Andrew P; Hueter, Robert E

    2015-05-01

    The study of functional trade-offs is important if a structure, such as the cranium, serves multiple biological roles, and is, therefore, shaped by multiple selective pressures. The sphyrnid cephalofoil presents an excellent model for investigating potential trade-offs among sensory, neural, and feeding structures. In this study, hammerhead shark species were chosen to represent differences in head form through phylogeny. A combination of surface-based geometric morphometrics, computed tomography (CT) volumetric analysis, and phylogenetic analyses were utilized to investigate potential trade-offs within the head. Hammerhead sharks display a diversity of cranial morphologies where the position of the eyes and nares vary among species, with only minor changes in shape, position, and volume of the feeding apparatus through phylogeny. The basal winghead shark, Eusphyra blochii, has small anteriorly positioned eyes. Through phylogeny, the relative size and position of the eyes change, such that derived species have larger, more medially positioned eyes. The lateral position of the external nares is highly variable, showing no phylogenetic trend. Mouth size and position are conserved, remaining relatively unchanged. Volumetric CT analyses reveal no trade-offs between the feeding apparatus and the remaining cranial structures. The few trade-offs were isolated to the nasal capsule volume's inverse correlation with braincase, chondrocranial, and total cephalofoil volume. Eye volume also decreased as cephalofoil width increased. These data indicate that despite considerable changes in head shape, much of the head is morphologically conserved through sphyrnid phylogeny, particularly the jaw cartilages and their associated feeding muscles, with shape change and morphological trade-offs being primarily confined to the lateral wings of the cephalofoil and their associated sensory structures. © 2015 Wiley Periodicals, Inc.

  6. Characterization of the Tetrahymena ribozyme folding pathway using the kinetic footprinting reagent peroxynitrous acid.

    Science.gov (United States)

    Chaulk, S G; MacMillan, A M

    2000-01-11

    Large RNAs fold into complex structures which determine their biological activities. A full understanding of both RNA structure and dynamics will include the description of the pathways by which these structures are formed. Kinetic footprinting [Sclavi, B., et al. (1997) J. Mol. Biol. 266, 144-159] has been shown to be a powerful method for the study of dynamic processes involving RNA. Here we describe the use of a readily available reagent, peroxynitrous acid, as a kinetic footprinting tool for the study of RNA folding. Hydroxyl radicals generated from this reagent were used to footprint the Tetrahymena ribozyme during its magnesium-dependent folding-in agreement with synchroton X-ray footprinting [Sclavi, B., et al. (1998) Science 279, 1940-1943] and oligonucleotide/hybridization cleavage experiments [Zarrinkar, P. P., and Williamson, J. R. (1994) Science 265, 918-924], this work suggests an ordered, hierarchical folding pathway for the ribozyme. Several slow steps in the folding pathway were observed in the peroxynitrous acid footprinting, but none of these corresponded to the rate-determining step of folding. This suggests that the formation of the global, protected structure is followed by one or more slow local rearrangements to yield the final active structure. These studies illustrate the utility of peroxynitrous acid as a reagent for the elucidation of RNA folding pathways and the study of RNA dynamics.

  7. Ribozyme Catalysis with a Twist: Active State of the Twister Ribozyme in Solution Predicted from Molecular Simulation.

    Science.gov (United States)

    Gaines, Colin S; York, Darrin M

    2016-03-09

    We present results from molecular dynamics simulations and free energy calculations of the twister ribozyme at different stages along the reaction path to gain insight into its mechanism. The results, together with recent biochemical experiments, provide support for a mechanism involving general-acid catalysis by a conserved adenine residue in the active site. Although adenine has been previously implicated as a general acid acting through the N1 position in other ribozymes such as the hairpin and VS ribozymes, in the twister ribozyme there may be a twist. Biochemical experiments suggest that general acid catalysis may occur through the N3 position, which has never before been implicated in this role; however, currently, there is a lack of a detailed structural model for the active state of the twister ribozyme in solution that is consistent with these and other experiments. Simulations in a crystalline environment reported here are consistent with X-ray crystallographic data, and suggest that crystal packing contacts trap the RNA in an inactive conformation with U-1 in an extruded state that is incompatible with an in-line attack to the scissile phosphate. Simulations in solution, on the other hand, reveal this region to be dynamic and able to adopt a conformation where U-1 is stacked with G33. In this state, the nucleophile is in line with the scissile phosphate, and the N1 position of G33 and N3 position of A1 are poised to act as a general base and acid, respectively, as supported by mutational experiments. Free energy calculations further predict the electrostatic environment causes a shift of the microscopic pKa at the N3 position of A1 toward neutrality by approximately 5 pKa units. These results offer a unified interpretation of a broad range of currently available experimental data that points to a novel mode of general acid catalysis through the N3 position of an adenine nucleobase, thus expanding the repertoire of known mechanistic strategies employed by

  8. Crystal structure and mechanistic investigation of the twister ribozyme.

    Science.gov (United States)

    Liu, Yijin; Wilson, Timothy J; McPhee, Scott A; Lilley, David M J

    2014-09-01

    We present a crystal structure at 2.3-Å resolution of the recently described nucleolytic ribozyme twister. The RNA adopts a previously uncharacterized compact fold based on a double-pseudoknot structure, with the active site at its center. Eight highly conserved nucleobases stabilize the core of the ribozyme through the formation of one Watson-Crick and three noncanonical base pairs, and the highly conserved adenine 3' of the scissile phosphate is bound in the major groove of an adjacent pseudoknot. A strongly conserved guanine nucleobase directs its Watson-Crick edge toward the scissile phosphate in the crystal structure, and mechanistic evidence supports a role for this guanine as either a general base or acid in a concerted, general acid-base-catalyzed cleavage reaction.

  9. Prebiotic Factors Influencing the Activity of a Ligase Ribozyme

    Directory of Open Access Journals (Sweden)

    Fabrizio Anella

    2017-04-01

    Full Text Available An RNA-lipid origin of life scenario provides a plausible route for compartmentalized replication of an informational polymer and subsequent division of the container. However, a full narrative to form such RNA protocells implies that catalytic RNA molecules, called ribozymes, can operate in the presence of self-assembled vesicles composed of prebiotically relevant constituents, such as fatty acids. Hereby, we subjected a newly engineered truncated variant of the L1 ligase ribozyme, named tL1, to various environmental conditions that may have prevailed on the early Earth with the objective to find a set of control parameters enabling both tL1-catalyzed ligation and formation of stable myristoleic acid (MA vesicles. The separate and concurrent effects of temperature, concentrations of Mg2+, MA, polyethylene glycol and various solutes were investigated. The most favorable condition tested consists of 100 mM NaCl, 1 mM Mg2+, 5 mM MA, and 4 °C temperature, whereas the addition of Mg2+-chelating solutes, such as citrate, tRNAs, aspartic acid, and nucleoside triphosphates severely inhibits the reaction. These results further solidify the RNA-lipid world hypothesis and stress the importance of using a systems chemistry approach whereby a wide range of prebiotic factors interfacing with ribozymes are considered.

  10. Reconciling Ligase Ribozyme Activity with Fatty Acid Vesicle Stability

    Directory of Open Access Journals (Sweden)

    Fabrizio Anella

    2014-12-01

    Full Text Available The “RNA world” and the “Lipid world” theories for the origin of cellular life are often considered incompatible due to the differences in the environmental conditions at which they can emerge. One obstacle resides in the conflicting requirements for divalent metal ions, in particular Mg2+, with respect to optimal ribozyme activity, fatty acid vesicle stability and protection against RNA strand cleavage. Here, we report on the activity of a short L1 ligase ribozyme in the presence of myristoleic acid (MA vesicles at varying concentrations of Mg2+. The ligation rate is significantly lower at low-Mg2+ conditions. However, the loss of activity is overcompensated by the increased stability of RNA leading to a larger amount of intact ligated substrate after long reaction periods. Combining RNA ligation assays with fatty acid vesicles we found that MA vesicles made of 5 mM amphiphile are stable and do not impair ligase ribozyme activity in the presence of approximately 2 mM Mg2+. These results provide a scenario in which catalytic RNA and primordial membrane assembly can coexist in the same environment.

  11. The Novel Chemical Mechanism of the Twister Ribozyme.

    Science.gov (United States)

    Wilson, Timothy J; Liu, Yijin; Domnick, Christof; Kath-Schorr, Stephanie; Lilley, David M J

    2016-05-18

    We describe the multifactorial origins of catalysis by the twister ribozyme. We provide evidence that the adenine immediately 3' to the scissile phosphate (A1) acts as a general acid. Substitution of ring nitrogen atoms indicates that very unusually the N3 of A1 is the proton donor to the oxyanion leaving group. A1 is accommodated in a specific binding pocket that raises its pKa toward neutrality, juxtaposes its N3 with the O5' to be protonated, and helps create the in-line trajectory required for nucleophilic attack. A1 performs general acid catalysis while G33 acts as a general base. A 100-fold stereospecific phosphorothioate effect at the scissile phosphate is consistent with a significant stabilization of the transition state by the ribozyme, and functional group substitution at G33 indicates that its exocyclic N2 interacts directly with the scissile phosphate. A model of the ribozyme active site is proposed that accommodates these catalytic strategies.

  12. An mRNA is capped by a 2', 5' lariat catalyzed by a group I-like ribozyme

    DEFF Research Database (Denmark)

    Nielsen, Henrik; Westhof, Eric; Johansen, Steinar

    2005-01-01

    Twin-ribozyme introns are formed by two ribozymes belonging to the group I family and occur in some ribosomal RNA transcripts. The group I-like ribozyme, GIR1, liberates the 5' end of a homing endonuclease messenger RNA in the slime mold Didymium iridis. We demonstrate that this cleavage occurs...

  13. Global phylogeography of the scalloped hammerhead shark (Sphyrna lewini).

    Science.gov (United States)

    Duncan, K M; Martin, A P; Bowen, B W; DE Couet, H G

    2006-07-01

    Large marine fishes typically have little population genetic structure. The exceptions are associated with sedentary behaviour, disjunct distributions, or reproductive philopatry. Scalloped hammerhead sharks (Sphyrna lewini) incorporate the contrasting traits of oceanic habitat (usually associated with high dispersal) and possible fidelity to nursery grounds (for reproductive females). To evaluate the expectations of these contrasting behaviours, we examined the global genetic structure of S. lewini based on collections (n = 271 individuals) from 20 nursery areas. A 548-bp fragment of mitochondrial DNA control region revealed 22 polymorphic sites, 24 haplotypes, and three lineages distinguished by 2.56-3.77% sequence divergence. Coalescence analyses based on a provisional molecular clock indicate an origin in the Indo-West Pacific with late Pleistocene radiations into the central Pacific (Hawaii) and eastern Pacific (Central America), as well as recent interchange between oceans via southern Africa. Population subdivisions are strong (overall Phi(ST) = 0.749, P 10). We conclude that nursery populations linked by continuous coastline have high connectivity, but that oceanic dispersal by females is rare. Although we cannot rule out philopatry to natal nurseries, oceanic barriers appear to have a much stronger influence on the genetic architecture of this species and may indicate a mechanism for recent evolutionary radiations in the genus Sphyrna.

  14. Kinematics and critical swimming speed of juvenile scalloped hammerhead sharks

    Science.gov (United States)

    Lowe

    1996-01-01

    Kinematics and critical swimming speed (Ucrit) of juvenile scalloped hammerhead sharks Sphyrna lewini were measured in a Brett-type flume (635 l). Kinematic parameters were also measured in sharks swimming in a large pond for comparison with those of sharks swimming in the flume. Sharks in the flume exhibited a mean Ucrit of 65±11 cm s-1 (± s.d.) or 1.17±0.21 body lengths per second (L s-1), which are similar to values for other species of sharks. In both the flume and pond, tailbeat frequency (TBF) and stride length (LS) increased linearly with increases in relative swimming speed (Urel=body lengths traveled per second). In the flume, tailbeat amplitude (TBA) decreased with increasing speed whereas TBA did not change with speed in the pond. Differences in TBF and LS between sharks swimming in the flume and the pond decreased with increases in Urel. Sharks swimming at slow speeds (e.g. 0.55 L s-1) in the pond had LS 19 % longer and TBF 21 % lower than sharks in the flume at the same Urel. This implies that sharks in the flume expended more energy while swimming at comparable velocities. Comparative measurements of swimming kinematics from sharks in the pond can be used to correct for effects of the flume on shark swimming kinematics and energetics.

  15. Engineering integrated digital circuits with allosteric ribozymes for scaling up molecular computation and diagnostics.

    Science.gov (United States)

    Penchovsky, Robert

    2012-10-19

    Here we describe molecular implementations of integrated digital circuits, including a three-input AND logic gate, a two-input multiplexer, and 1-to-2 decoder using allosteric ribozymes. Furthermore, we demonstrate a multiplexer-decoder circuit. The ribozymes are designed to seek-and-destroy specific RNAs with a certain length by a fully computerized procedure. The algorithm can accurately predict one base substitution that alters the ribozyme's logic function. The ability to sense the length of RNA molecules enables single ribozymes to be used as platforms for multiple interactions. These ribozymes can work as integrated circuits with the functionality of up to five logic gates. The ribozyme design is universal since the allosteric and substrate domains can be altered to sense different RNAs. In addition, the ribozymes can specifically cleave RNA molecules with triplet-repeat expansions observed in genetic disorders such as oculopharyngeal muscular dystrophy. Therefore, the designer ribozymes can be employed for scaling up computing and diagnostic networks in the fields of molecular computing and diagnostics and RNA synthetic biology.

  16. Mapping the Chemical Space of the RNA Cleavage and Its Implications for Ribozyme Catalysis

    Czech Academy of Sciences Publication Activity Database

    Mlýnský, V.; Kührová, P.; Jurečka, P.; Šponer, Jiří; Otyepka, M.; Banáš, Pavel

    2017-01-01

    Roč. 121, č. 48 (2017), s. 10828-10840 ISSN 1520-6106 R&D Projects: GA ČR GAP208/12/1878 Institutional support: RVO:68081707 Keywords : delta-virus ribozyme * self-cleaving ribozymes Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.177, year: 2016

  17. Generation and Development of RNA Ligase Ribozymes with Modular Architecture Through “Design and Selection”

    Directory of Open Access Journals (Sweden)

    Yuki Fujita

    2010-08-01

    Full Text Available In vitro selection with long random RNA libraries has been used as a powerful method to generate novel functional RNAs, although it often requires laborious structural analysis of isolated RNA molecules. Rational RNA design is an attractive alternative to avoid this laborious step, but rational design of catalytic modules is still a challenging task. A hybrid strategy of in vitro selection and rational design has been proposed. With this strategy termed “design and selection,” new ribozymes can be generated through installation of catalytic modules onto RNA scaffolds with defined 3D structures. This approach, the concept of which was inspired by the modular architecture of naturally occurring ribozymes, allows prediction of the overall architectures of the resulting ribozymes, and the structural modularity of the resulting ribozymes allows modification of their structures and functions. In this review, we summarize the design, generation, properties, and engineering of four classes of ligase ribozyme generated by design and selection.

  18. Hammerhead Shark Research Immersion Program: Experiential Learning Leads to Lasting Educational Benefits

    Science.gov (United States)

    Handler, Alex; Duncan, Kanesa

    2006-01-01

    High school students (n = 45) participated in a 5-day research immersion study on juvenile scalloped hammerhead sharks in Kaneohe Bay, Oahu, Hawaii. Self-surveys were used to evaluate scientific concepts and skills taught during the program. There was a significant shift in students' perceived level of understanding for all categories of concepts…

  19. Design principles for ligand-sensing, conformation-switching ribozymes.

    Directory of Open Access Journals (Sweden)

    Xi Chen

    2009-12-01

    Full Text Available Nucleic acid sensor elements are proving increasingly useful in biotechnology and biomedical applications. A number of ligand-sensing, conformational-switching ribozymes (also known as allosteric ribozymes or aptazymes have been generated by some combination of directed evolution or rational design. Such sensor elements typically fuse a molecular recognition domain (aptamer with a catalytic signal generator (ribozyme. Although the rational design of aptazymes has begun to be explored, the relationships between the thermodynamics of aptazyme conformational changes and aptazyme performance in vitro and in vivo have not been examined in a quantitative framework. We have therefore developed a quantitative and predictive model for aptazymes as biosensors in vitro and as riboswitches in vivo. In the process, we have identified key relationships (or dimensionless parameters that dictate aptazyme performance, and in consequence, established equations for precisely engineering aptazyme function. In particular, our analysis quantifies the intrinsic trade-off between ligand sensitivity and the dynamic range of activity. We were also able to determine how in vivo parameters, such as mRNA degradation rates, impact the design and function of aptazymes when used as riboswitches. Using this theoretical framework we were able to achieve quantitative agreement between our models and published data. In consequence, we are able to suggest experimental guidelines for quantitatively predicting the performance of aptazyme-based riboswitches. By identifying factors that limit the performance of previously published systems we were able to generate immediately testable hypotheses for their improvement. The robust theoretical framework and identified optimization parameters should now enable the precision design of aptazymes for biotechnological and clinical applications.

  20. Applicability of PM3 to transphosphorylation reaction path: Toward designing a minimal ribozyme

    Science.gov (United States)

    Manchester, John I.; Shibata, Masayuki; Setlik, Robert F.; Ornstein, Rick L.; Rein, Robert

    1993-01-01

    A growing body of evidence shows that RNA can catalyze many of the reactions necessary both for replication of genetic material and the possible transition into the modern protein-based world. However, contemporary ribozymes are too large to have self-assembled from a prebiotic oligonucleotide pool. Still, it is likely that the major features of the earliest ribozymes have been preserved as molecular fossils in the catalytic RNA of today. Therefore, the search for a minimal ribozyme has been aimed at finding the necessary structural features of a modern ribozyme (Beaudry and Joyce, 1990). Both a three-dimensional model and quantum chemical calculations are required to quantitatively determine the effects of structural features of the ribozyme on the reaction it catalyzes. Using this model, quantum chemical calculations must be performed to determine quantitatively the effects of structural features on catalysis. Previous studies of the reaction path have been conducted at the ab initio level, but these methods are limited to small models due to enormous computational requirements. Semiempirical methods have been applied to large systems in the past; however, the accuracy of these methods depends largely on a simple model of the ribozyme-catalyzed reaction, or hydrolysis of phosphoric acid. We find that the results are qualitatively similar to ab initio results using large basis sets. Therefore, PM3 is suitable for studying the reaction path of the ribozyme-catalyzed reaction.

  1. Design and Experimental Evolution of trans-Splicing Group I Intron Ribozymes

    Directory of Open Access Journals (Sweden)

    Ulrich F. Müller

    2017-01-01

    Full Text Available Group I intron ribozymes occur naturally as cis-splicing ribozymes, in the form of introns that do not require the spliceosome for their removal. Instead, they catalyze two consecutive trans-phosphorylation reactions to remove themselves from a primary transcript, and join the two flanking exons. Designed, trans-splicing variants of these ribozymes replace the 3′-portion of a substrate with the ribozyme’s 3′-exon, replace the 5′-portion with the ribozyme’s 5′-exon, or insert/remove an internal sequence of the substrate. Two of these designs have been evolved experimentally in cells, leading to variants of group I intron ribozymes that splice more efficiently, recruit a cellular protein to modify the substrate’s gene expression, or elucidate evolutionary pathways of ribozymes in cells. Some of the artificial, trans-splicing ribozymes are promising as tools in therapy, and as model systems for RNA evolution in cells. This review provides an overview of the different types of trans-splicing group I intron ribozymes that have been generated, and the experimental evolution systems that have been used to improve them.

  2. Pseudoknot Formation Seeds the Twister Ribozyme Cleavage Reaction Coordinate.

    Science.gov (United States)

    Vušurović, Nikola; Altman, Roger B; Terry, Daniel S; Micura, Ronald; Blanchard, Scott C

    2017-06-21

    The twister RNA is a recently discovered nucleolytic ribozyme that is present in both bacteria and eukarya. While its biological role remains unclear, crystal structure analyses and biochemical approaches have revealed critical features of its catalytic mechanism. Here, we set out to explore dynamic aspects of twister RNA folding along the cleavage reaction coordinate. To do so, we have employed both bulk and single-molecule fluorescence resonance energy transfer (FRET) methods to investigate a set of twister RNAs with labels strategically positioned at communicating segments. The data reveal that folding of the central pseudoknot (T1), the most crucial structural determinant to promote cleavage, exhibits reversible opening and closing dynamics at physiological Mg2+ concentration. Uncoupled folding, in which T1 formation precedes structuring for closing of stem P1, was confirmed using pre-steady-state three-color smFRET experiments initiated by Mg2+ injection. This finding suggests that the folding path of twister RNA requires proper orientation of the substrate prior to T1 closure such that the U5-A6 cleavage site becomes embraced to achieve its cleavage competent conformation. We also find that the cleaved 3'-fragment retains its compacted pseudoknot fold, despite the absence of the phylogenetically conserved stem P1, rationalizing the poor turnover efficiency of the twister ribozyme.

  3. Group I Intron Internal Guide Sequence Binding Strength as a Component of Ribozyme Network Formation

    Directory of Open Access Journals (Sweden)

    Laura Elizabeth Satterwhite

    2016-09-01

    Full Text Available Origins-of-life research requires searching for a plausible transition from simple chemicals to larger macromolecules that can both hold information and catalyze their own production. We have previously shown that some group I intron ribozymes possess the ability to help synthesize other ribozyme genotypes by recombination reactions in small networks in an autocatalytic fashion. By simplifying these recombination reactions, using fluorescent anisotropy, we quantified the thermodynamic binding strength between two nucleotides of two group I intron RNA fragments for all 16 possible genotype combinations. We provide evidence that the binding strength (KD between the 3-nucleotide internal guide sequence (IGS of one ribozyme and its complement in another is correlated to the catalytic ability of the ribozyme. This work demonstrates that one can begin to deconstruct the thermodynamic basis of information in prebiotic RNA systems.

  4. Pressure modulates the self-cleavage step of the hairpin ribozyme

    Science.gov (United States)

    Schuabb, Caroline; Kumar, Narendra; Pataraia, Salome; Marx, Dominik; Winter, Roland

    2017-03-01

    The ability of certain RNAs, denoted as ribozymes, to not only store genetic information but also catalyse chemical reactions gave support to the RNA world hypothesis as a putative step in the development of early life on Earth. This, however, might have evolved under extreme environmental conditions, including the deep sea with pressures in the kbar regime. Here we study pressure-induced effects on the self-cleavage of hairpin ribozyme by following structural changes in real-time. Our results suggest that compression of the ribozyme leads to an accelerated transesterification reaction, being the self-cleavage step, although the overall process is retarded in the high-pressure regime. The results reveal that favourable interactions between the reaction site and neighbouring nucleobases are strengthened under pressure, resulting therefore in an accelerated self-cleavage step upon compression. These results suggest that properly engineered ribozymes may also act as piezophilic biocatalysts in addition to their hitherto known properties.

  5. Pressure modulates the self-cleavage step of the hairpin ribozyme

    Science.gov (United States)

    Schuabb, Caroline; Kumar, Narendra; Pataraia, Salome; Marx, Dominik; Winter, Roland

    2017-01-01

    The ability of certain RNAs, denoted as ribozymes, to not only store genetic information but also catalyse chemical reactions gave support to the RNA world hypothesis as a putative step in the development of early life on Earth. This, however, might have evolved under extreme environmental conditions, including the deep sea with pressures in the kbar regime. Here we study pressure-induced effects on the self-cleavage of hairpin ribozyme by following structural changes in real-time. Our results suggest that compression of the ribozyme leads to an accelerated transesterification reaction, being the self-cleavage step, although the overall process is retarded in the high-pressure regime. The results reveal that favourable interactions between the reaction site and neighbouring nucleobases are strengthened under pressure, resulting therefore in an accelerated self-cleavage step upon compression. These results suggest that properly engineered ribozymes may also act as piezophilic biocatalysts in addition to their hitherto known properties. PMID:28358002

  6. Long-distance communication in the HDV ribozyme: insights from molecular dynamics and experiments.

    Science.gov (United States)

    Veeraraghavan, Narayanan; Bevilacqua, Philip C; Hammes-Schiffer, Sharon

    2010-09-10

    The hepatitis delta virus ribozyme is a small, self-cleaving RNA with a compact tertiary structure and buried active site that is important in the life cycle of the virus. The ribozyme's function in nature is to cleave an internal phosphodiester bond and linearize concatemers during rolling circle replication. Crystal structures of the ribozyme have been solved in both pre-cleaved and post-cleaved (product) forms and reveal an intricate network of interactions that conspire to catalyze bond cleavage. In addition, extensive biochemical studies have been performed to work out a mechanism for bond cleavage in which C75 and a magnesium ion catalyze the reaction by general acid-base chemistry. One issue that has remained unclear in this ribozyme and in other ribozymes is the nature of long-distance communication between peripheral regions of the RNA and the buried active site. We performed molecular dynamics simulations on the hepatitis delta virus ribozyme in the product form and assessed communication between a distal structural portion of the ribozyme-the protonated C41 base triple-and the active site containing the critical C75. We varied the ionization state of C41 in both the wild type and a C41 double mutant variant and determined the impact on the active site. In all four cases, effects at the active site observed in the simulations agree with experimental studies on ribozyme activity. Overall, these studies indicate that small functional RNAs have the potential to communicate interactions over long distances and that wild-type RNAs may have evolved ways to prevent such interactions from interfering with catalysis. Copyright 2010 Elsevier Ltd. All rights reserved.

  7. Rapid formation of a solvent-inaccessible core in the Neurospora Varkud satellite ribozyme

    Science.gov (United States)

    Hiley, Shawna L.; Collins, Richard A.

    2001-01-01

    We have used hydroxyl radicals generated by decomposition of peroxynitrous acid to study Mg2+-dependent structure and folding of the Varkud satellite (VS) ribozyme. Protection from radical cleavage shows the existence of a solvent-inaccessible core, which includes nucleotides near two three-helix junctions, the kissing interaction between stem–loops I and V and other nucleotides, most of which have also been implicated as important for folding or activity. Kinetic folding experiments showed that the ribozyme folds very quickly, with the observed protections completely formed within 2 s of addition of MgCl2. In mutants that disrupt the kissing interaction or entirely remove stem–loop I, which contains the cleavage site, nucleotides in the three-helix junctions and a subset of those elsewhere remain protected. Unlike smaller ribozymes, the VS ribozyme retains a significant amount of structure in the absence of its substrate. Protections that depend on proper interaction between the substrate and the rest ribozyme map to a region previously proposed as the active site of the ribozyme and along both sides of helix II, identifying candidate sites of docking for the substrate helix. PMID:11574478

  8. Unwinding the twister ribozyme: from structure to mechanism.

    Science.gov (United States)

    Gebetsberger, Jennifer; Micura, Ronald

    2017-05-01

    The twister ribozyme motif has been identified by bioinformatic means very recently. Currently, four crystal structures with ordered active sites together with a series of chemical and biochemical data provide insights into how this RNA accomplishes its efficient self-cleavage. Of particular interest for a mechanistic proposal are structural distinctions observed in the active sites that concern the conformation of the U-A cleavage site dinucleotide (in-line alignment of the attacking 2'-O nucleophile to the to-be-cleaved PO5' bond versus suboptimal alignments) as well as the presence/absence of Mg2+ ions at the scissile phosphate. All structures support the notion that an active site guanine and the conserved adenine at the cleavage site are important contributors to cleavage chemistry, likely being involved in general acid base catalysis. Evidence for innersphere coordination of a Mg2+ ion to the pro-S nonbridging oxygen of the scissile phosphate stems from two of the four crystal structures. Together with the finding of thio/rescue effects for phosphorothioate substrates, this suggests the participation of divalent ions in the overall catalytic strategy employed by twister ribozymes. In this context, it is notable that twister retains wild-type activity when the phylogenetically conserved stem P1 is deleted, able to cleave a single nucleotide only. WIREs RNA 2017, 8:e1402. doi: 10.1002/wrna.1402 For further resources related to this article, please visit the WIREs website. © 2016 The Authors. WIREs RNA published by Wiley Periodicals, Inc.

  9. Hotspots within hotspots? Hammerhead shark movements around Wolf Island, Galapagos Marine Reserve

    OpenAIRE

    Hearn, Alex; Ketchum, James; Klimley, A. Peter; Espinoza, Eduardo; Peñaherrera, Cesar

    2010-01-01

    Are pelagic species such as sharks and tuna distributed homogenously or heterogeneously in the oceans? Large assemblages of these species have been observed at seamounts and offshore islands in the eastern tropical Pacific, which are considered hotspots of pelagic biodiversity. Is the species distribution uniform at these hotspots or do species aggregate at a finer spatial scale at these sites? We employed three techniques to demonstrate that the aggregations of scalloped hammerhead sharks, S...

  10. Functional involvement of G8 in the hairpin ribozyme cleavage mechanism

    Science.gov (United States)

    Pinard, Robert; Hampel, Ken J.; Heckman, Joyce E.; Lambert, Dominic; Chan, Philip A.; Major, Francois; Burke, John M.

    2001-01-01

    The catalytic determinants for the cleavage and ligation reactions mediated by the hairpin ribozyme are integral to the polyribonucleotide chain. We describe experiments that place G8, a critical guanosine, at the active site, and point to an essential role in catalysis. Cross-linking and modeling show that formation of a catalytic complex is accompanied by a conformational change in which N1 and O6 of G8 become closely apposed to the scissile phosphodiester. UV cross-linking, hydroxyl-radical footprinting and native gel electrophoresis indicate that G8 variants inhibit the reaction at a step following domain association, and that the tertiary structure of the inactive complex is not measurably altered. Rate–pH profiles and fluorescence spectroscopy show that protonation at the N1 position of G8 is required for catalysis, and that modification of O6 can inhibit the reaction. Kinetic solvent isotope analysis suggests that two protons are transferred during the rate-limiting step, consistent with rate-limiting cleavage chemistry involving concerted deprotonation of the attacking 2′-OH and protonation of the 5′-O leaving group. We propose mechanistic models that are consistent with these data, including some that invoke a novel keto–enol tautomerization. PMID:11707414

  11. Hotspots within hotspots? Hammerhead shark movements around Wolf Island, Galapagos Marine Reserve.

    Science.gov (United States)

    Hearn, Alex; Ketchum, James; Klimley, A Peter; Espinoza, Eduardo; Peñaherrera, Cesar

    2010-01-01

    Are pelagic species such as sharks and tuna distributed homogenously or heterogeneously in the oceans? Large assemblages of these species have been observed at seamounts and offshore islands in the eastern tropical Pacific, which are considered hotspots of pelagic biodiversity. Is the species distribution uniform at these hotspots or do species aggregate at a finer spatial scale at these sites? We employed three techniques to demonstrate that the aggregations of scalloped hammerhead sharks, Sphyrna lewini, and other pelagic species were confined to the southeastern corner of Wolf Island in the Galapagos Marine Reserve. Coded ultrasonic transmitters were placed on individuals at this site and at another aggregation site at Darwin Island, separated from Wolf by 40 km, and they were detected by monitors moored at the southeastern corner of Wolf Island and rarely by monitors deployed at other sites around the island. Hammerhead sharks, carrying depth-sensing continual transmitters, were tracked for two-day periods in a vessel and shown to reside a disproportionately large fraction of their time at the southeastern corner. Visual censuses were carried out seasonally at the eight monitor sites at Wolf Island, recording the abundance of one species of tuna, four species of jacks, and a number of other species. The highest diversity and abundance of these species occurred in the southeastern corner of the island. Our results support the use of hammerhead sharks as indicator and umbrella species for pelagic hotspots on a fine scale.

  12. The Hydrodynamics and Odorant Transport Phenomena of Olfaction in the Hammerhead Shark

    Science.gov (United States)

    Rygg, Alex; Craven, Brent

    2013-11-01

    The hammerhead shark possesses a unique head morphology that is thought to facilitate enhanced olfactory performance. The olfactory organs, located at the distal ends of the cephalofoil, contain numerous lamellae that increase the surface area for olfaction. Functionally, for the shark to detect chemical stimuli, water-borne odors must reach the olfactory sensory epithelium that lines these lamellae. Thus, odorant transport from the aquatic environment to the sensory epithelium is the first critical step in olfaction. Here we investigate the hydrodynamics and odorant transport phenomena of olfaction in the hammerhead shark based on an anatomically-accurate reconstruction of the head and olfactory chamber from high-resolution micro-CT and MRI scans of a cadaver specimen. Computational fluid dynamics (CFD) simulations of water flow in the reconstructed model reveal the external and internal hydrodynamics of olfaction during swimming. Odorant transport in the olfactory organ is investigated using a multi-scale approach, whereby molecular dynamics (MD) simulations are used to calculate odorant partition coefficients that are subsequently utilized in macro-scale CFD simulations of odorant deposition. The hydrodynamic and odorant transport results are used to elucidate several important features of olfactory function in the hammerhead shark.

  13. Inducible knockdown of Plasmodium gene expression using the glmS ribozyme.

    Directory of Open Access Journals (Sweden)

    Parichat Prommana

    Full Text Available Conventional reverse genetic approaches for study of Plasmodium malaria parasite gene function are limited, or not applicable. Hence, new inducible systems are needed. Here we describe a method to control P. falciparum gene expression in which target genes bearing a glmS ribozyme in the 3' untranslated region are efficiently knocked down in transgenic P. falciparum parasites in response to glucosamine inducer. Using reporter genes, we show that the glmS ribozyme cleaves reporter mRNA in vivo leading to reduction in mRNA expression following glucosamine treatment. Glucosamine-induced ribozyme activation led to efficient reduction of reporter protein, which could be rapidly reversed by removing the inducer. The glmS ribozyme was validated as a reverse-genetic tool by integration into the essential gene and antifolate drug target dihydrofolate reductase-thymidylate synthase (PfDHFR-TS. Glucosamine treatment of transgenic parasites led to rapid and efficient knockdown of PfDHFR-TS mRNA and protein. PfDHFR-TS knockdown led to a growth/arrest mutant phenotype and hypersensitivity to pyrimethamine. The glmS ribozyme may thus be a tool for study of essential genes in P. falciparum and other parasite species amenable to transfection.

  14. Crystal structure of Pistol, a class of self-cleaving ribozyme

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, Laura A.; Wang, Jimin; Steitz, Thomas A. (Yale)

    2017-01-17

    Small self-cleaving ribozymes have been discovered in all evolutionary domains of life. They can catalyze site-specific RNA cleavage, and as a result, they have relevance in gene regulation. Comparative genomic analysis has led to the discovery of a new class of small self-cleaving ribozymes named Pistol. We report the crystal structure of Pistol at 2.97-Å resolution. Our results suggest that the Pistol ribozyme self-cleavage mechanism likely uses a guanine base in the active site pocket to carry out the phosphoester transfer reaction. The guanine G40 is in close proximity to serve as the general base for activating the nucleophile by deprotonating the 2'-hydroxyl to initiate the reaction (phosphoester transfer). Furthermore, G40 can also establish hydrogen bonding interactions with the nonbridging oxygen of the scissile phosphate. The proximity of G32 to the O5' leaving group suggests that G32 may putatively serve as the general acid. The RNA structure of Pistol also contains A-minor interactions, which seem to be important to maintain its tertiary structure and compact fold. Our findings expand the repertoire of ribozyme structures and highlight the conserved evolutionary mechanism used by ribozymes for catalysis.

  15. A novel chimeric ribozyme vector produces potent inhibition of ICAM-1 expression on ischemic vascular endothelium.

    Science.gov (United States)

    Sonnenday, Christopher J; Warren, Daniel S; Cooke, Sara K; Dietz, Harry C; Montgomery, Robert A

    2004-12-01

    Inhibition of intercellular adhesion molecule-1 (ICAM-1) expression can ameliorate the inflammation induced by ischemia-reperfusion injury (IRI) in animal models. However, current strategies to reduce ICAM-1 expression have been limited by the lack of stability, poor specificity, and the transient nature of synthesized regulatory molecules (antisense/ribozyme). A chimeric expression vector was generated by fusing a ribozyme targeting sequence against ICAM-1 to stabilizing stem-loop structures and nuclear localization signals that are components of endogenous U1 small nuclear RNA. Oligonucleotide scanning was used to predict accessible sites for targeting within the rat ICAM-1 transcript. Efficacy of the chimeric ribozyme vector was tested by transfection of rat aortic endothelial (RAE) cells (in vitro) and intraportal delivery in a rat hepatic IRI model (in vivo). Transfection of RAE cells with the chimeric ribozyme vector produced potent and specific inhibition of ICAM-1 mRNA and protein levels by >65%. This reduction in ICAM-1 expression was accompanied by a proportional decrease in neutrophil adhesion to RAE cells. In vivo intraportal delivery of the chimeric targeting vector to rats sustaining hepatic IRI produced a marked reduction in ICAM-1 expression on liver endothelium after reperfusion. A chimeric ribozyme vector effectively inhibited ICAM-1 expression in vascular endothelial cells and in rat liver following IRI, demonstrating a novel gene targeting technique that may be ideally suited to clinical applications aimed at ameliorating IRI. Copyright 2004 John Wiley & Sons, Ltd.

  16. Active site labeling of G8 in the hairpin ribozyme: implications for structure and mechanism.

    Science.gov (United States)

    Thomas, Jason M; Perrin, David M

    2006-12-27

    There is mounting evidence that suggests that general acid/base catalysis is operative in the hairpin ribozyme, with analogy to the protein enzyme RNaseA. Nevertheless, the extent of general base catalysis as well as the identity of the specific chemical groups responsible remains the subject of some controversy. An affinity label has previously been used to alkylate histidine 12 (His12), the active general base in RNaseA. To date, no such experiment has been applied to a ribozyme. We have synthesized the analogous affinity label for the hairpin ribozyme with an electrophilic 2'-bromoacetamide group in lieu of the 2'-hydroxyl (2'OH) at the substrate cleavage site and show that guanosine 8 (G8) of the hairpin ribozyme is specifically alkylated, most likely at the N1 position. This evidence strongly implicates N1 of G8 in active site chemistry. By direct analogy to RNase A, these findings could be consistent with the hypothesis that deprotonated G8 residue functions as a general base in the hairpin ribozyme. Other mechanistic possibilities for N1 of G8 such as indirect general base catalysis mediated by a water molecule or transition state stabilization could also be consistent with our findings.

  17. Flanking sequences with an essential role in hydrolysis of a self-cleaving group I-like ribozyme

    DEFF Research Database (Denmark)

    Einvik, C; Nielsen, Henrik; Nour, R

    2000-01-01

    DiGIR1 is a group I-like ribozyme derived from the mobile twin ribozyme group I intron DiSSU1 in the nuclear ribosomal DNA of the myxomycete Didymium iridis. This ribozyme is responsible for intron RNA processing in vitro and in vivo at two internal sites close to the 5'-end of the intron endo......-nuclease open reading frame and is a unique example of a group I ribozyme with an evolved biological function. DiGIR1 is the smallest functional group I ribozyme known from nature and has an unusual core organization including the 6 bp P15 pseudoknot. Here we report results of functional and structural analyses...

  18. Identification of young-of-the-year great hammerhead shark Sphyrna mokarran in northern Florida and South Carolina.

    Science.gov (United States)

    Barker, A M; Frazier, B S; Bethea, D M; Gold, J R; Portnoy, D S

    2017-08-01

    Two sharks, visually identified in the field as young-of-the-year (YOY) scalloped hammerhead Sphyrna lewini, were identified as great hammerhead Sphyrna mokarran based on nuclear-encoded single nucleotide polymorphisms (SNP) and sequences of mtDNA. Individuals were captured and released in Bulls Bay, SC, and Saint Joseph Bay, FL, in 2013 and 2014, respectively. These findings indicate S. mokarran may be pupping in or around these areas and highlight new regions that may be a productive focus for future research on early life history of S. mokarran. © 2017 The Fisheries Society of the British Isles.

  19. Maternal offloading of organochlorine contaminants in the yolk-sac placental scalloped hammerhead shark (Sphyrna lewini).

    Science.gov (United States)

    Lyons, Kady; Adams, Douglas H

    2015-04-01

    Elasmobranchs are a group of animals that typically occupy upper trophic levels in food webs and have a propensity to accumulate high contaminant concentrations. To date, few studies have investigated maternal offloading processes in sharks, despite the fact that this process represents a substantial source of exposure for young sharks and is a significant pathway for contaminant redistribution within marine ecosystems. Comparable to mammalian systems, scalloped hammerhead sharks (Sphyrna lewini) utilize a yolk-sac placental strategy to nourish young in utero, which may allow females to transfer contaminants to young. Organic contaminants (PCBs and chlorinated pesticides) were measured in livers of both females and males from several age classes that were collected from U.S. Atlantic waters, including two near-term pregnant females and their embryos. Adult female hammerheads (n = 3) were found to have lower levels of PCBs compared to the younger, adult male (mean ± SD, 11.1 ± 1.0 vs. 22.8 μg g(-1) lw), but had substantially higher concentrations of pesticides (4.1 ± 0.9 vs. 1.9 μg g(-1) lw). Embryos from the two litters (n = 36) had similar levels of summed organic contaminant concentrations (4.6 ± 0.9 μg g(-1) lw) and pregnant females were estimated to offload approximately 0.03-2.3% of their hepatic contaminant load to offspring. While the potential health impacts of these transferred contaminants is unknown, this is the first study to demonstrate that scalloped hammerheads are exposed to a substantial amount of contaminants prior to birth and document maternal offloading of organochlorines in a pseudo-placental shark species. Therefore, future research should continue to investigate the potential adverse effects these contaminants have on elasmobranch physiology.

  20. Purification and Identification of Antioxidant Peptides from Protein Hydrolysate of Scalloped Hammerhead (Sphyrna lewini Cartilage

    Directory of Open Access Journals (Sweden)

    Xue-Rong Li

    2017-03-01

    Full Text Available The aim of this study was to purify and identify peptides with antioxidant properties from protein hydrolysate of scalloped hammerhead (Sphyrna lewini cartilage. Cartilaginous proteins of the scalloped hammerhead were extracted by guanidine hydrochloride, and three antioxidant peptides, named enzymolysis peptide of scalloped hammerhead cartilage A (SCPE-A, SCPE-B and SCPE-C, were subsequently isolated from the hydrolysate of the cartilaginous proteins using ultrafiltration and chromatography. The amino acid sequences of SCPE-A, SCPE-B and SCPE-C were identified as Gly-Pro-Glu (GPE, Gly-Ala-Arg-Gly-Pro-Gln (GARGPQ, and Gly-Phe-Thr-Gly-Pro-Pro-Gly-Phe-Asn-Gly (GFTGPPGFNG, with molecular weights of 301.30 Da, 584.64 Da and 950.03 Da, respectively. As per in vitro activity testing, SCPE-A, SCPE-B and SCPE-C exhibited strong scavenging activities on 2,2-diphenyl-1-picrylhydrazyl radicals (DPPH• (half elimination ratio (EC50 2.43, 2.66 and 1.99 mg/mL, hydroxyl radicals (HO• (EC50 0.28, 0.21 and 0.15 mg/mL, 2,2′-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid radicals (ABTS+• (EC50 0.24, 0.18 and 0.29 mg/mL, and superoxide anion radicals ( O 2 − • (EC50 0.10, 0.14 and 0.11 mg/mL. In addition, SCPE-A showed inhibition activity similar to butylated hydroxytoluene (BHT in lipid peroxidation in a linoleic acid model system. The amino acid residues of Gly, Pro and Phe could positively influence the antioxidant activities of GPE, GARGPQ and GFTGPPGFNG. These results suggested that GPE, GARGPQ and GFTGPPGFNG might serve as potential antioxidants and be used as food additives and functional foods.

  1. Long distance communication in the HDV ribozyme: Insights from molecular dynamics and experiments

    OpenAIRE

    Veeraraghavan, Narayanan; Bevilacqua, Philip C.; Hammes-Schiffer, Sharon

    2010-01-01

    The hepatitis delta virus (HDV) ribozyme is a small self-cleaving RNA with a compact tertiary structure and buried active site that is important in the life cycle of the virus. The ribozyme’s function in nature is to cleave an internal phosphodiester bond and linearize concatemers during rolling circle replication. Crystal structures of the ribozyme have been solved in both pre-cleaved and post-cleaved (product) forms and reveal an intricate network of interactions that conspire to catalyze b...

  2. 76 FR 72891 - Endangered and Threatened Wildlife; 90-Day Finding on a Petition To List the Scalloped Hammerhead...

    Science.gov (United States)

    2011-11-28

    ... standards on extinction risk and impacts or threats discussed above. Distribution and Life History of the... WildEarth Guardians and Friends of Animals to list the scalloped hammerhead shark (Sphyrna lewini) as..., or DPS is ``endangered'' if it is in danger of extinction throughout all or a significant portion of...

  3. 78 FR 24701 - Endangered and Threatened Wildlife; 90-Day Finding on Petitions To List the Great Hammerhead...

    Science.gov (United States)

    2013-04-26

    ... indicate that hypoxic occurrences and dead zones, a result of growing human populations, urban pollution... dead zones (Driggers and Hoffmayer, personal communication, 2013). In addition, both petitions assert... al., 2011; Bester, n.d.). In the western Atlantic Ocean, the great hammerhead range extends from...

  4. Population and individual foraging patterns of two hammerhead sharks using carbon and nitrogen stable isotopes.

    Science.gov (United States)

    Loor-Andrade, P; Galván-Magaña, F; Elorriaga-Verplancken, F R; Polo-Silva, C; Delgado-Huertas, A

    2015-05-15

    Individual foraging behavior is an important variable of predators commonly studied at the population level. Some hammerhead shark species play a significant role in the marine ecosystem as top consumers. In this context, stable isotope analysis allows us to infer some ecological metrics and patterns that cannot usually be obtained using traditional methods. We determined the isotopic composition (δ(13)C and δ(15)N values) of dorsal muscle and vertebrae of Sphyrna lewini and Sphyrna zygaena using a continuous-flow system consisting of an elemental analyzer combined with a Delta Plus XL mass spectrometer. Foraging variability by sex and by individual was inferred from the isotopic values. There were no significant differences in the isotopic values of muscle samples between sexes, but there were differences between species. The trophic niche breadth of the two species was similar and overlap was low. A low niche overlap was observed between S. lewini individual vertebrae. We found differences in the δ(15)N values of S. zygaena vertebrae, with lower values in the first group of samples. Despite these hammerhead shark species inhabiting the same area, there was low trophic niche overlap between species and individuals, due to different individual foraging strategies, according to the carbon and nitrogen isotopic profiles obtained. The use of tissues that retain lifetime isotopic information is useful to complement studies on trophic ecology. Copyright © 2015 John Wiley & Sons, Ltd.

  5. Fishers' ecological knowledge of smalleye hammerhead, Sphyrna tudes , in a tropical estuary

    Directory of Open Access Journals (Sweden)

    Vinicius J. Giglio

    Full Text Available ABSTRACT Coastal hammerheads have suffered from overexploitation and environmental degradation. We interviewed 79 artisanal fishers to verify fishery aspects, temporal changes in catches and biological aspects of the smalleye hammerhead, Sphyrna tudes , in a marine protected area on Abrolhos Bank, Brazil. Data were compared between three generations of fishers: young, middle-aged and old. Fishers' age varied between 17 and 88 years. We verified significant reductions in the weight of individuals caught by younger fishers. The main types of fishing gear used to catch S. tudes were gill nets and longlines. Overfishing through gill nets and trawl fisheries were mentioned as the cause of S. tudes population collapse in the region. The shark's diet as reported by fishers consisted of fish, crab and shrimp; austral summer was the reproductive season. A strong similarity was verified between fishers' knowledge and biological data. We suggest as plausible strategies to conserve the local population of S. tudes the reduction of net fisheries impact through zoning and establishment of no take areas. These steps can help to initiate the recovery of this depleted species.

  6. Conservation Genetics of the Scalloped Hammerhead Shark in the Pacific Coast of Colombia.

    Science.gov (United States)

    Quintanilla, Sonia; Gómez, Alberto; Mariño-Ramírez, Camila; Sorzano, Carolina; Bessudo, Sandra; Soler, German; Bernal, Jaime E; Caballero, Susana

    2015-01-01

    Previous investigations of the population genetics of the scalloped hammerhead sharks (Sphyrna lewini) in the Eastern Tropical Pacific have lacked information about nursery areas. Such areas are key to promoting conservation initiatives that can protect young sharks from threats such as overfishing. Here, we investigated the genetic diversity, phylogeography, and connectivity of S. lewini found in 3 areas of Colombia's Pacific coast: around Malpelo Island and in 2 National Natural Parks on the Colombian Pacific mainland (Sanquianga and Ensenada de Utría). We analyzed mtDNA control region (CR) sequences and genotyped 15 microsatellite loci in 137 samples of adults and juveniles. The mtDNA analyses showed haplotypes shared between the Colombian Pacific individuals sampled in this investigation and other areas in the Eastern Tropical Pacific, the Indo-Pacific, and with sequences previously reported in Colombia (Buenaventura Port), as well as 4 unique haplotypes. Population assignment and paternity analyses detected 3 parent-offspring pairs between Malpelo and Sanquianga and 1 between Malpelo and Utría. These results indicate high genetic connectivity between Malpelo Island and the Colombian Pacific coast, suggesting that these 2 areas are nurseries for S. lewini. This is, to our knowledge, the first evidence of nursery areas identified for the scalloped hammerhead shark anywhere in the world. Additional conservation planning may be required to protect these nursery habitats of this endangered shark species. © The American Genetic Association 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  7. The complement system of elasmobranches revealed by liver transcriptome analysis of a hammerhead shark, Sphyrna zygaena.

    Science.gov (United States)

    Goshima, Masayuki; Sekiguchi, Reo; Matsushita, Misao; Nonaka, Masaru

    2016-08-01

    Comprehensive studies of the complement genes in basal vertebrates have revealed that cyclostomes have apparently primitive complement systems whereas bony fish have well-developed complement systems comparable to those of mammals. Here we have performed liver transcriptome analysis of a hammerhead shark, Sphyrna zygaeana, to elucidate the early history of vertebrate complement evolution. Identified genes were; one C1qB, one C1r, one C1s, one MASP-1/-3, one MASP-2, two factor B/C2, one C3, three C4, one C5, one C6, one C7, one C8A, three C8B, one C8G, one C9, two factor I and one S protein. No MBL, ficolin, C1qA or C1qC were found. These results indicate that the lectin, classical, alternative and lytic pathways were established in the common ancestor of jawed vertebrates. In addition to the absence of MBL and ficolin, the MASP transcripts lacked the serine protease domain, suggesting that the lectin pathway was lost in the hammerhead shark lineage. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Probing fast ribozyme reactions under biological conditions with rapid quench-flow kinetics.

    Science.gov (United States)

    Bingaman, Jamie L; Messina, Kyle J; Bevilacqua, Philip C

    2017-05-01

    Reaction kinetics on the millisecond timescale pervade the protein and RNA fields. To study such reactions, investigators often perturb the system with abiological solution conditions or substrates in order to slow the rate to timescales accessible by hand mixing; however, such perturbations can change the rate-limiting step and obscure key folding and chemical steps that are found under biological conditions. Mechanical methods for collecting data on the millisecond timescale, which allow these perturbations to be avoided, have been developed over the last few decades. These methods are relatively simple and can be conducted on affordable and commercially available instruments. Here, we focus on using the rapid quench-flow technique to study the fast reaction kinetics of RNA enzymes, or ribozymes, which often react on the millisecond timescale under biological conditions. Rapid quench of ribozymes is completely parallel to the familiar hand-mixing approach, including the use of radiolabeled RNAs and fractionation of reactions on polyacrylamide gels. We provide tips on addressing and preventing common problems that can arise with the rapid-quench technique. Guidance is also offered on ensuring the ribozyme is properly folded and fast-reacting. We hope that this article will facilitate the broader use of rapid-quench instrumentation to study fast-reacting ribozymes under biological reaction conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. The glmS Ribozyme Cofactor is a General Acid-Base Catalyst

    Science.gov (United States)

    Viladoms, Julia; Fedor, Martha J.

    2012-01-01

    The glmS ribozyme is the first natural self-cleaving ribozyme known to require a cofactor. The D-glucosamine-6-phosphate (GlcN6P) cofactor has been proposed to serve as a general acid, but its role in the catalytic mechanism has not been established conclusively. We surveyed GlcN6P-like molecules for their ability to support self-cleavage of the glmS ribozyme and found a strong correlation between the pH dependence of the cleavage reaction and the intrinsic acidity of the cofactors. For cofactors with low binding affinities the contribution to rate enhancement was proportional to their intrinsic acidity. This linear free-energy relationship between cofactor efficiency and acid dissociation constants is consistent with a mechanism in which the cofactors participate directly in the reaction as general acid-base catalysts. A high value for the Brønsted coefficient (β ~ 0.7) indicates that a significant amount of proton transfer has already occurred in the transition state. The glmS ribozyme is the first self-cleaving RNA to use an exogenous acid-base catalyst. PMID:23113700

  10. The structure of a nucleolytic ribozyme that employs a catalytic metal ion.

    Science.gov (United States)

    Liu, Yijin; Wilson, Timothy J; Lilley, David M J

    2017-05-01

    The TS ribozyme (originally called "twister sister") is a catalytic RNA. We present a crystal structure of the ribozyme in a pre-reactive conformation. Two co-axial helical stacks are organized by a three-way junction and two tertiary contacts. Five divalent metal ions are directly coordinated to RNA ligands, making important contributions to the RNA architecture. The scissile phosphate lies in a quasihelical loop region that is organized by a network of hydrogen bonding. A divalent metal ion is directly bound to the nucleobase 5' to the scissile phosphate, with an inner-sphere water molecule positioned to interact with the O2' nucleophile. The rate of ribozyme cleavage correlated in a log-linear manner with divalent metal ion pKa, consistent with proton transfer in the transition state, and we propose that the bound metal ion is a likely general base for the cleavage reaction. Our data indicate that the TS ribozyme functions predominantly as a metalloenzyme.

  11. Wobble pairs of the HDV ribozyme play specific roles in stabilization of active site dynamics

    Czech Academy of Sciences Publication Activity Database

    Sripathi, K.N.; Banáš, P.; Réblová, K.; Šponer, Jiří; Otyepka, M.; Walter, Nils G.

    2015-01-01

    Roč. 17, č. 8 (2015), s. 5887-5900 ISSN 1463-9076 R&D Projects: GA ČR GAP208/12/1878 Institutional support: RVO:68081707 Keywords : HEPATITIS-DELTA-VIRUS * SELF-CLEAVING RIBOZYMES * ACID-BASE CATALYSIS Subject RIV: BO - Biophysics Impact factor: 4.449, year: 2015

  12. Complete mitochondrial genome of the scalloped hammerhead Sphyrna lewini (Carcharhiniformes: Sphyrnidae).

    Science.gov (United States)

    Chen, Xiao; Xiang, Dan; Xu, Yuziwei; Shi, Xiaofang

    2015-08-01

    The complete mitochondrial genome of the endangered scalloped hammerhead Sphyrna lewini was firstly determined in this study. It is 16,726 bp in length with the typical gene composition and orders in vertebrates. The overall base composition is 31.4% A, 26.3% C, 13.2% G and 29.1% T. Two start codon (ATG and GTG) and three stop codon (TAG, AGA and TAA/TA/T) patterns were found in protein-coding genes. Except for the tRNA-Ser2, the remaining 21 tRNAs can be folded into the typical cloverleaf structure. The control region possess the highest A + T content (66.1%) and lowest G content (12.6%) among all mitochondrial partitions.

  13. Great hammerhead sharks swim on their side to reduce transport costs.

    Science.gov (United States)

    Payne, Nicholas L; Iosilevskii, Gil; Barnett, Adam; Fischer, Chris; Graham, Rachel T; Gleiss, Adrian C; Watanabe, Yuuki Y

    2016-07-26

    Animals exhibit various physiological and behavioural strategies for minimizing travel costs. Fins of aquatic animals play key roles in efficient travel and, for sharks, the functions of dorsal and pectoral fins are considered well divided: the former assists propulsion and generates lateral hydrodynamic forces during turns and the latter generates vertical forces that offset sharks' negative buoyancy. Here we show that great hammerhead sharks drastically reconfigure the function of these structures, using an exaggerated dorsal fin to generate lift by swimming rolled on their side. Tagged wild sharks spend up to 90% of time swimming at roll angles between 50° and 75°, and hydrodynamic modelling shows that doing so reduces drag-and in turn, the cost of transport-by around 10% compared with traditional upright swimming. Employment of such a strongly selected feature for such a unique purpose raises interesting questions about evolutionary pathways to hydrodynamic adaptations, and our perception of form and function.

  14. New microsatellite loci for the endangered scalloped hammerhead shark, Sphyrna lewini.

    Science.gov (United States)

    Nance, Holly A; Daly-Engel, Toby S; Marko, Peter B

    2009-05-01

    We isolated 15 microsatellite markers for the scalloped hammerhead shark, Sphyrna lewini. Loci were tested on 80 specimens of S. lewini from four Eastern Pacific samples. The number of alleles per locus ranged from 6 to 31 (mean = 14). Observed and expected levels of heterozygosity per locus ranged from 0.39 to 0.91 (mean = 0.70) and from 0.54 to 0.90 (mean = 0.76), respectively. No pairs of loci were in gametic disequilibrium after Bonferroni correction of α. One locus showed significantly lower heterozygosity than expected under Hardy-Weinberg proportions in two populations, possibly caused by null alleles. © 2009 The Authors. Journal compilation © 2009 Blackwell Publishing Ltd.

  15. Fusarium solani fungal infection of the lateral line canal system in captive scalloped hammerhead sharks (Sphyrna lewini) in Hawaii.

    Science.gov (United States)

    Crow, G L; Brock, J A; Kaiser, S

    1995-10-01

    Two of five scalloped hammerhead sharks (Sphyrna lewini) captured May 1987 in Hawaii (USA) developed granulomatous exudative mycotic dermatitis localized in the lateral line canal system. The lesion initially was noted in the cephalic canals, but over a period of months extended into the lateral canal. Fusarium solani and Vibrio spp. were isolated from the canal exudate of both sharks. Bacterial colonies were not observed in the canal walls or surrounding tissues. Fusarium solani infection resulted in a chronic physical and behavioral deterioration of the two sharks; one shark was euthanized in September 1988 and the other in July 1989. This is the first report of Fusarium solani infection in the lateral line canal system and the third account in hammerhead sharks.

  16. Vulnerability to longline fisheries of three hammerhead shark Sphyrna species in the south-western and equatorial Atlantic Ocean.

    Science.gov (United States)

    Bezerra, N P A; Travassos, P; Hazin, F H V

    2016-08-01

    Catch and effort data from 29 418 longline sets from Brazilian tuna longline vessels operating in the south-western and equatorial Atlantic Ocean between 2004 and 2011 were analysed to investigate the distribution, catch rate and size of three species of hammerhead sharks (Sphyrna lewini, Sphyrna mokarran and Sphyrna zygaena). During that period, 6172 hammerhead sharks were caught. Among the elasmobranchs, the highest percentage of hammerhead sharks were caught in 2007, when they accounted for 3·90% of the group, while the lowest value of 0·40% was recorded in 2010. In general, the spatial distribution of the mean catch per unit effort (CPUE) by years and quarters showed a trend of higher catches near the equatorial region and in southern Brazil. The nominal mean CPUE was 0·12 Sphyrna spp. 1000(-1) hooks, with the highest value being recorded in 2007 (0·30 Sphyrna spp. 1000(-1) hooks). The standardized yearly CPUE estimated by a generalized linear model assuming a zero inflated negative binomial (ZINB) distribution were not much different from nominal values. Of the 205 sexed specimens, 117 were females and 88 were males, resulting in a sex ratio with a predominance of females (1·30:1·00), although not statistically significant. The total length of females ranged from 1200 to 2800 mm and of males from 1100 to 3100 mm. Juvenile hammerhead sharks represented 82 and 54% of the sexed female and male specimens, respectively. © 2016 The Fisheries Society of the British Isles.

  17. Feeding strategy of the night shark (Carcharhinus signatus) and scalloped hammerhead shark (Sphyrna lewini) near seamounts off northeastern Brazil

    OpenAIRE

    Teodoro Vaske Júnior; Carolus Maria Vooren; Rosangela Paula Lessa

    2009-01-01

    A total of 425 stomachs of night shark (Carcharhinus signatus), and 98 stomachs of scalloped hammerhead shark (Sphyrna lewini), from longline and surface gillneters near seamounts off northeastern Brazil, were analysed between 1992 and 1999. Both predators prey upon reef and benthopelagic fishes, migrant cephalopods and deep water crustaceans, showing similar feeding niches (Schoener Index T=0.75). The great prey richness of the diets may reflect the fact that the marine food web for these sp...

  18. Rapid formation of a solvent-inaccessible core in the Neurospora Varkud satellite ribozyme

    OpenAIRE

    Hiley, Shawna L.; Collins, Richard A.

    2001-01-01

    We have used hydroxyl radicals generated by decomposition of peroxynitrous acid to study Mg2+-dependent structure and folding of the Varkud satellite (VS) ribozyme. Protection from radical cleavage shows the existence of a solvent-inaccessible core, which includes nucleotides near two three-helix junctions, the kissing interaction between stem–loops I and V and other nucleotides, most of which have also been implicated as important for folding or activity. Kinetic folding experiments showed t...

  19. Disparate HDV ribozyme crystal structures represent intermediates on a rugged free-energy landscape

    Czech Academy of Sciences Publication Activity Database

    Sripathi, K.N.; Tay, W.W.; Banáš, P.; Otyepka, M.; Šponer, Jiří; Walter, N. G.

    2014-01-01

    Roč. 20, č. 7 (2014), s. 1112-1128 ISSN 1355-8382 R&D Projects: GA MŠk(CZ) ED1.1.00/02.0068; GA ČR(CZ) GAP208/12/1878 Institutional support: RVO:68081707 Keywords : time-resolved FRET * steady-state FRET * small ribozyme Subject RIV: BO - Biophysics Impact factor: 4.936, year: 2014

  20. Structural principles of RNA catalysis in a 2'-5' lariat-forming ribozyme.

    Science.gov (United States)

    Carlomagno, Teresa; Amata, Irene; Codutti, Luca; Falb, Melanie; Fohrer, Jörg; Masiewicz, Pawel; Simon, Bernd

    2013-03-20

    RNA-catalyzed lariat formation is present in both eukaryotes and prokaryotes. To date we lack structural insights into the catalytic mechanism of lariat-forming ribozymes. Here, we study an artificial 2'-5' AG1 lariat-forming ribozyme that shares the sequence specificity of lariat formation with the pre-mRNA splicing reaction. Using NMR, we solve the structure of the inactive state of the ribozyme in the absence of magnesium. The reaction center 5'-guanosine appears to be part of a helix with an exceptionally widened major groove, while the lariat-forming A48 is looped out at the apex of a pseudoknot. The model of the active state built by mutational analysis, molecular modeling, and small-angle X-ray scattering suggests that A48 is recognized by a conserved adenosine, juxtaposed to the 5'-guanosine in one base-pair step distance, while the G1-N7 coordinates a magnesium ion essential for the activation of the nucleophile. Our findings offer implications for lariat formation in RNA enzymes including the mechanism of the recognition of the branch-site adenosine.

  1. Thirty-five years of research into ribozymes and nucleic acid catalysis: where do we stand today?

    Science.gov (United States)

    Müller, Sabine; Appel, Bettina; Balke, Darko; Hieronymus, Robert; Nübel, Claudia

    2016-01-01

    Since the discovery of the first catalytic RNA in 1981, the field of ribozyme research has developed from the discovery of catalytic RNA motifs in nature and the elucidation of their structures and catalytic mechanisms, into a field of engineering and design towards application in diagnostics, molecular biology and medicine. Owing to the development of powerful protocols for selection of nucleic acid catalysts with a desired functionality from random libraries, the spectrum of nucleic acid supported reactions has greatly enlarged, and importantly, ribozymes have been accompanied by DNAzymes. Current areas of research are the engineering of allosteric ribozymes for artificial regulation of gene expression, the design of ribozymes and DNAzymes for medicinal and environmental diagnostics, and the demonstration of RNA world relevant ribozyme activities. In addition, new catalytic motifs or novel genomic locations of known motifs continue to be discovered in all branches of life by the help of high-throughput bioinformatic approaches. Understanding the biological role of the catalytic RNA motifs widely distributed in diverse genetic contexts belongs to the big challenges of future RNA research.

  2. Structure-based insights into self-cleavage by a four-way junctional twister-sister ribozyme.

    Science.gov (United States)

    Zheng, Luqian; Mairhofer, Elisabeth; Teplova, Marianna; Zhang, Ye; Ma, Jinbiao; Patel, Dinshaw J; Micura, Ronald; Ren, Aiming

    2017-10-30

    Here we report on the crystal structure and cleavage assays of a four-way junctional twister-sister self-cleaving ribozyme. Notably, 11 conserved spatially separated loop nucleotides are brought into close proximity at the ribozyme core through long-range interactions mediated by hydrated Mg2+ cations. The C62-A63 step at the cleavage site adopts a splayed-apart orientation, with flexible C62 directed outwards, whereas A63 is directed inwards and anchored by stacking and hydrogen-bonding interactions. Structure-guided studies of key base, sugar, and phosphate mutations in the twister-sister ribozyme, suggest contributions to the cleavage chemistry from interactions between a guanine at the active site and the non-bridging oxygen of the scissile phosphate, a feature found previously also for the related twister ribozyme. Our four-way junctional pre-catalytic structure differs significantly in the alignment at the cleavage step (splayed-apart vs. base-stacked) and surrounding residues and hydrated Mg2+ ions relative to a reported three-way junctional pre-catalytic structure of the twister-sister ribozyme.

  3. Ribozyme Mediated gRNA Generation for In Vitro and In Vivo CRISPR/Cas9 Mutagenesis

    Science.gov (United States)

    Ng, Ashley Shu Mei; Ingham, Philip W.

    2016-01-01

    CRISPR/Cas9 is now regularly used for targeted mutagenesis in a wide variety of systems. Here we report the use of ribozymes for the generation of gRNAs both in vitro and in zebrafish embryos. We show that incorporation of ribozymes increases the types of promoters and number of target sites available for mutagenesis without compromising mutagenesis efficiency. We have tested this by comparing the efficiency of mutagenesis of gRNA constructs with and without ribozymes and also generated a transgenic zebrafish expressing gRNA using a heat shock promoter (RNA polymerase II-dependent promoter) that was able to induce mutagenesis of its target. Our method provides a streamlined approach to test gRNA efficiency as well as increasing the versatility of conditional gene knock out in zebrafish. PMID:27832146

  4. Ribozyme Mediated gRNA Generation for In Vitro and In Vivo CRISPR/Cas9 Mutagenesis.

    Directory of Open Access Journals (Sweden)

    Raymond Teck Ho Lee

    Full Text Available CRISPR/Cas9 is now regularly used for targeted mutagenesis in a wide variety of systems. Here we report the use of ribozymes for the generation of gRNAs both in vitro and in zebrafish embryos. We show that incorporation of ribozymes increases the types of promoters and number of target sites available for mutagenesis without compromising mutagenesis efficiency. We have tested this by comparing the efficiency of mutagenesis of gRNA constructs with and without ribozymes and also generated a transgenic zebrafish expressing gRNA using a heat shock promoter (RNA polymerase II-dependent promoter that was able to induce mutagenesis of its target. Our method provides a streamlined approach to test gRNA efficiency as well as increasing the versatility of conditional gene knock out in zebrafish.

  5. Phylogeny of hammerhead sharks (Family Sphyrnidae) inferred from mitochondrial and nuclear genes.

    Science.gov (United States)

    Lim, Douglas D; Motta, Philip; Mara, Kyle; Martin, Andrew P

    2010-05-01

    Hammerhead sharks (Family Sphyrnidae) get their name from their laterally expanded, dorsal-ventrally compressed head, a structure referred to as the cephalofoil. Species within the family vary for head size and shape and for body size in ways that are functionally significant. Here we infer the phylogeny for all species within the family based on analysis of mitochondrial and nuclear genes amounting to 6292 base pairs. Mixed model Bayesian analysis of the concatenated data and Bayesian estimation of the species tree (BEST) converged on the same topology of the relationships. Shimodaira-Hasegawa tests revealed that all previously proposed hypotheses could be refuted by the data. The new hypothesis for the group suggests that the ancestor of all extant sharks was large (>200 cms) and that small body size probably evolved twice at different times and places. Moreover, the results suggest that once the cephalofoil evolved, it underwent divergent evolution in different lineages presumably in response to unique selective regimes. Copyright 2010 Elsevier Inc. All rights reserved.

  6. Asymmetric hemoglobins, their thiol content, and blood glutathione of the scalloped hammerhead shark, Sphyrna lewini.

    Science.gov (United States)

    Dafré, A L; Reischl, E

    1997-03-01

    Starch gel electrophoresis pH 8.6, or PAGE pH 8.9, of the scalloped hammerhead shark hemolysates showed three hemoglobins (Hb). An additional Hb between the two most mobile electrophoretic components was seen in starch gel electrophoresis, pH 8.1, and also in highly loaded PAGE gels. The relative concentration of these Hbs was variable among individuals, when accessed at pH 8.1. Dilution of hemolysates led to a redistribution of the Hb tetramer subunits. Under denaturing conditions, the unfractionated hemolysate was resolved in 3 Hb subunits. Isolated Hbs, named SL I-SL IV, showed unusual subunit compositions: SL I, the least mobile, is "b3c"; SL II is "a2bc"; SL III and SL IV are composed only by "a" subunits. Hemoglobins in the whole hemolysate have an average of two reactive cysteines per tetramer, which were not easily S-thiolated by glutathione, as is the case for related species. After hemoglobin denaturation, six additional -SH groups were titrated by Ellman's reagent. Methemoglobin content was low in the erythrocytes of nine examined specimens, 1.13 +/- 1.90%. High values for total erythrocyte glutathione (GSH) were found: 4.5 +/- 0.7 mM; n = 7. The ratio of 1.4 +/- 0.4 GSH/Hb is higher than usually reported for mammalians.

  7. Effects of fasting and refeeding on intestinal cell proliferation and apoptosis in hammerhead shark (Sphyrna lewini

    Directory of Open Access Journals (Sweden)

    Hideya Takahashi

    2014-04-01

    Full Text Available Objective: To examine the effects of fasting and refeeding on intestinal cell proliferation and apoptosis in an opportunistic predator, hammerhead shark (Sphyrna lewini of elasmobranch fishes which are among the earliest known extant groups of vertebrates to have the valvular intestine typical for the primitive species. Methods: Animals were euthanized after 5-10 d of fasting or feeding, or after 10-day fasting and 5-day refeeding. Intestinal apoptosis and cell proliferation were assessed by using oligonucleotide detection assay, terminal deoxynucleotidyl transferase dUTP nick end labeling staining, and immunohistochemistry of proliferating cells nuclear antigen. Results: Plasma levels of cholesterol and glucose were reduced by fasting. Intestinal apoptosis generally decreased during fasting. Numerous apoptotic cells were observed around the tips of the villi, primarily in the epithelium in the fed sharks, whereas fewer labeled nuclei were detected in the epithelium of fasted sharks. Refeeding returned intestinal apoptosis to the level in the fed sharks. Proliferating cells were observed in the epithelium around the troughs of the villi and greater in number in fed sharks, whereas fewer labeled nuclei were detected in fasted sharks. Conclusions: The cell turnover is modified in both intestinal epithelia of the shark and the murines by fasting/feeding, but in opposite directions. The difference may reflect the feeding ecology of the elasmobranchs, primitive intermittent feeders.

  8. Mercury and selenium bioaccumulation in the smooth hammerhead shark, Sphyrna zygaena Linnaeus, from the Mexican Pacific Ocean

    OpenAIRE

    Escobar Sánchez, Ofelia; Galván Magaña, Felipe; Rosiles Martínez, R.

    2010-01-01

    We analyzed total mercury and selenium bioaccumulation in muscle tissue and cartilage fibers (fins) from smooth hammerhead shark, Sphyrna zygaena, caught off Baja California Sur, Mexico. In muscle tissue, the mercury concentration ranged from 0.005 to 1.93 μg g−1 ww (wet weight), which falls within the safety limits for food set by international agencies (Hg > 1.0 μg g−1 ww). Only one specimen showed a mercury value that exceeded this limit. In fins, the mercury bioaccumulation was lower (...

  9. Demographic processes underlying subtle patterns of population structure in the scalloped hammerhead shark, Sphyrna lewini.

    Science.gov (United States)

    Nance, Holly A; Klimley, Peter; Galván-Magaña, Felipe; Martínez-Ortíz, Jimmy; Marko, Peter B

    2011-01-01

    Genetic diversity (θ), effective population size (N(e)), and contemporary levels of gene flow are important parameters to estimate for species of conservation concern, such as the globally endangered scalloped hammerhead shark, Sphyrna lewini. Therefore, we have reconstructed the demographic history of S. lewini across its Eastern Pacific (EP) range by applying classical and coalescent population genetic methods to a combination of 15 microsatellite loci and mtDNA control region sequences. In addition to significant population genetic structure and isolation-by-distance among seven coastal sites between central Mexico and Ecuador, the analyses revealed that all populations have experienced a bottleneck and that all current values of θ are at least an order of magnitude smaller than ancestral θ, indicating large decreases in N(e) (θ = 4N(e)μ), where μ is the mutation rate. Application of the isolation-with-migration (IM) model showed modest but significant genetic connectivity between most sampled sites (point estimates of Nm = 0.1-16.7), with divergence times (t) among all populations significantly greater than zero. Using a conservative (i.e., slow) fossil-based taxon-specific phylogenetic calibration for mtDNA mutation rates, posterior probability distributions (PPDs) for the onset of the decline in N(e) predate modern fishing in this region. The cause of decline over the last several thousand years is unknown but is highly atypical as a post-glacial demographic history. Regardless of the cause, our data and analyses suggest that S. lewini was far more abundant throughout the EP in the past than at present.

  10. Demographic processes underlying subtle patterns of population structure in the scalloped hammerhead shark, Sphyrna lewini.

    Directory of Open Access Journals (Sweden)

    Holly A Nance

    Full Text Available Genetic diversity (θ, effective population size (N(e, and contemporary levels of gene flow are important parameters to estimate for species of conservation concern, such as the globally endangered scalloped hammerhead shark, Sphyrna lewini. Therefore, we have reconstructed the demographic history of S. lewini across its Eastern Pacific (EP range by applying classical and coalescent population genetic methods to a combination of 15 microsatellite loci and mtDNA control region sequences. In addition to significant population genetic structure and isolation-by-distance among seven coastal sites between central Mexico and Ecuador, the analyses revealed that all populations have experienced a bottleneck and that all current values of θ are at least an order of magnitude smaller than ancestral θ, indicating large decreases in N(e (θ = 4N(eμ, where μ is the mutation rate. Application of the isolation-with-migration (IM model showed modest but significant genetic connectivity between most sampled sites (point estimates of Nm = 0.1-16.7, with divergence times (t among all populations significantly greater than zero. Using a conservative (i.e., slow fossil-based taxon-specific phylogenetic calibration for mtDNA mutation rates, posterior probability distributions (PPDs for the onset of the decline in N(e predate modern fishing in this region. The cause of decline over the last several thousand years is unknown but is highly atypical as a post-glacial demographic history. Regardless of the cause, our data and analyses suggest that S. lewini was far more abundant throughout the EP in the past than at present.

  11. Melanoma Angiogenesis and Metastasis Modulated by Ribozyme Targeting of the Secreted Growth Factor Pleiotrophin

    Science.gov (United States)

    Czubayko, Frank; Schulte, Anke M.; Berchem, Guy J.; Wellstein, Anton

    1996-12-01

    Clinical and experimental evidence suggests that spreading of malignant cells from a localized tumor (metastasis) is directly related to the number of microvessels in the primary tumor. This tumor angiogenesis is thought to be mediated by tumor-cell-derived growth factors. However, most tumor cells express a multitude of candidate angiogenesis factors and it is difficult to decipher which of these are rate-limiting factors in vivo. Herein we use ribozyme targeting of pleiotrophin (PTN) in metastatic human melanoma cells to assess the significance of this secreted growth factor for angiogenesis and metastasis. As a model we used human melanoma cells (1205LU) that express high levels of PTN and metastasize from subcutaneous tumors to the lungs of experimental animals. In these melanoma cells, we reduced PTN mRNA and growth factor activity by transfection with PTN-targeted ribozymes and generated cell lines expressing different levels of PTN. We found that the reduction of PTN does not affect growth of the melanoma cells in vitro. In nude mice, however, tumor growth and angiogenesis were decreased in parallel with the reduced PTN levels and apoptosis in the tumors was increased. Concomitantly, the metastatic spread of the tumors from the subcutaneous site to the lungs was prevented. These studies support a direct link between tumor angiogenesis and metastasis through a secreted growth factor and identify PTN as a candidate factor that may be rate-limiting for human melanoma metastasis.

  12. Dissecting human cytomegalovirus gene function and capsid maturation by ribozyme targeting and electron cryomicroscopy.

    Science.gov (United States)

    Yu, Xuekui; Trang, Phong; Shah, Sanket; Atanasov, Ivo; Kim, Yong-Hwan; Bai, Yong; Zhou, Z Hong; Liu, Fenyong

    2005-05-17

    Human CMV (HCMV) is the leading viral cause of birth defects and causes one of the most common opportunistic infections among transplant recipients and AIDS patients. Cleavage of internal scaffolding proteins by the viral protease (Pr) occurs during HCMV capsid assembly. To gain insight into the mechanism of HCMV capsid maturation and the roles of the Pr in viral replication, an RNase P ribozyme was engineered to target the Pr mRNA and down-regulate its expression by >99%, generating premature Pr-minus capsids. Furthermore, scaffolding protein processing and DNA encapsidation were inhibited by 99%, and viral growth was reduced by 10,000-fold. 3D structural comparison of the Pr-minus and wild-type B capsids by electron cryomicroscopy, at an unprecedented 12.5-angstroms resolution, unexpectedly revealed that the structures are identical in their overall shape and organization. However, the Pr-minus capsid contains tenuous connections between the scaffold and the capsid shell, whereas the wild-type B capsid has extra densities in its core that may represent the viral Pr. Our findings indicate that cleavage of the scaffolding protein is not associated with the morphological changes that occur during capsid maturation. Instead, the protease appears to be required for DNA encapsidation and the subsequent maturation steps leading to infectious progeny. These results therefore provide key insights into an essential step of HCMV infection using an RNase P ribozyme-based inhibition strategy.

  13. Structural basis for the fast self-cleavage reaction catalyzed by the twister ribozyme.

    Science.gov (United States)

    Eiler, Daniel; Wang, Jimin; Steitz, Thomas A

    2014-09-09

    Twister is a recently discovered RNA motif that is estimated to have one of the fastest known catalytic rates of any naturally occurring small self-cleaving ribozyme. We determined the 4.1-Å resolution crystal structure of a twister sequence from an organism that has not been cultured in isolation, and it shows an ordered scissile phosphate and nucleotide 5' to the cleavage site. A second crystal structure of twister from Orzyza sativa determined at 3.1-Å resolution exhibits a disordered scissile phosphate and nucleotide 5' to the cleavage site. The core of twister is stabilized by base pairing, a large network of stacking interactions, and two pseudoknots. We observe three nucleotides that appear to mediate catalysis: a guanosine that we propose deprotonates the 2'-hydroxyl of the nucleotide 5' to the cleavage site and a conserved adenosine. We suggest the adenosine neutralizes the negative charge on a nonbridging phosphate oxygen atom at the cleavage site. The active site also positions the labile linkage for in-line nucleophilic attack, and thus twister appears to simultaneously use three strategies proposed for small self-cleaving ribozymes. The twister crystal structures (i) show its global structure, (ii) demonstrate the significance of the double pseudoknot fold, (iii) provide a possible hypothesis for enhanced catalysis, and (iv) illuminate the roles of all 10 highly conserved nucleotides of twister that participate in the formation of its small and stable catalytic pocket.

  14. Group I-like ribozymes with a novel core organization perform obligate sequential hydrolytic cleavages at two processing sites

    DEFF Research Database (Denmark)

    Einvik, C; Nielsen, Henrik; Westhof, E

    1998-01-01

    available GIR1 sequences and propose a common RNA secondary structure resembling that of group I splicing-ribozymes, but with some important differences. The GIR1s lack most peripheral sequence components, as well as a P1 segment, and, at approximately 160-190 nt, they are the smallest functional group I...

  15. Kinetics of HIV-1 long terminal repeat trans-activation. Use of intragenic ribozyme to assess rate-limiting steps

    NARCIS (Netherlands)

    Jeang, K. T.; Berkhout, B.

    1992-01-01

    We have examined, using self-cleaving ribozymes, the intracellular trans-activation kinetics of the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) by viral protein Tat. Experiments were designed to effect a competition (during RNA chain elongation) between cleavage of a

  16. A Mini-Twister Variant and Impact of Residues/Cations on the Phosphodiester Cleavage of this Ribozyme Class.

    Science.gov (United States)

    Košutić, Marija; Neuner, Sandro; Ren, Aiming; Flür, Sara; Wunderlich, Christoph; Mairhofer, Elisabeth; Vušurović, Nikola; Seikowski, Jan; Breuker, Kathrin; Höbartner, Claudia; Patel, Dinshaw J; Kreutz, Christoph; Micura, Ronald

    2015-12-07

    Nucleolytic ribozymes catalyze site-specific cleavage of their phosphodiester backbones. A minimal version of the twister ribozyme is reported that lacks the phylogenetically conserved stem P1 while retaining wild-type activity. Atomic mutagenesis revealed that nitrogen atoms N1 and N3 of the adenine-6 at the cleavage site are indispensable for cleavage. By NMR spectroscopy, a pKa value of 5.1 was determined for a (13) C2-labeled adenine at this position in the twister ribozyme, which is significantly shifted compared to the pKa of the same adenine in the substrate alone. This finding pinpoints at a potential role for adenine-6 in the catalytic mechanism besides the previously identified invariant guanine-48 and a Mg(2+) ion, both of which are directly coordinated to the non-bridging oxygen atoms of the scissile phosphate; for the latter, additional evidence stems from the observation that Mn(2+) or Cd(2+) accelerated cleavage of phosphorothioate substrates. The relevance of this metal ion binding site is further emphasized by a new 2.6 Å X-ray structure of a 2'-OCH3 -U5 modified twister ribozyme. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. SOME BIOLOGICAL ASPECTS OF SCALLOPED HAMMERHEAD SHARKS (Sphyrna lewini Griffith & Smith, 1834 CAUGHT FROM COASTAL FISHERIES IN THE EASTERN INDIAN OCEAN

    Directory of Open Access Journals (Sweden)

    Umi Chodrijah

    2015-12-01

    Full Text Available Indonesia has the largest chondrichthyan fishery in the world, with a reported of 105,000 and 118,000 tonnes landed in 2002 and 2003 respectively. Scalloped hammerhead shark was either targeted or by-catch from this fishery, mostly for its fins. Despite of the growing concern around the world, the availability of biological data of this species, especially in the Eastern Indian Ocean is still lacking. The objectives of this paper are to present some biological information (size composition and sex ratio of the scalloped hammerhead, from coastal fisheries in Eastern Indian Ocean. The data used for the analysis comprised of two components, i.e. survey data in 2010 (February, March, June, August, October and December and data from daily monitoring shark landing in 2013 (January to December. Substantially lower mean size, more immature sharks and more frequent of female caught over years showed that scalloped hammerhead shark in the Eastern Indian Ocean are facing intensive fishing pressure which could lead to overfishing. This could harm the sustainability of scalloped hammerhead shark resource in the long run. The relationship between clasper length and total length was positively correlated where every 5 cmTL increment on clasper length adding 51 cmTL on total length.

  18. Age and growth of the Scalloped Hammerhead shark, Sphyrna lewini (Griffith and Smith, 1834), from the southern Brazilian coast.

    Science.gov (United States)

    Kotas, J E; Mastrochirico, V; Petrere Junior, M

    2011-08-01

    Age and growth studies for the scalloped hammerhead shark, Sphyrna lewini (Griffith and Smith, 1834) caught along the southern Brazilian coast, were based on ring measurements of vertebrae sections of 115 males, 116 females and 14 unknown sexed sharks between 48 and 344 cm total length (TL). The von Bertalanffy growth models were best fit using back-calculated data. The growth parameters obtained for males, were L∞ = 266 cm; K = 0.05/year; L0 = 47 cm. For females, L∞ = 300 cm; K = 0.05/year; L0 = 51 cm. An adult female reached 217 cm TL and was 31.5 years old. On the other hand, an adult male was 29.5 years old and measured 234 cm TL. Longevity estimate for males and females was 55 years. Therefore, S. lewini is a long-lived fish. Ageing precision, based on the IAPE index, was 5.6%. Marginal Increment analysis based on MIR index from hammerheads smaller than 105 cm, compared with the percentual of opaque and hyaline bands found per month ageing whole vertebrae, showed an annual ring formation, i.e., in winter.

  19. The group I-like ribozyme DiGIR1 mediates alternative processing of pre-rRNA transcripts in Didymium iridis

    DEFF Research Database (Denmark)

    Vader, Anna; Johansen, Steinar; Nielsen, Henrik

    2002-01-01

    During starvation induced encystment, cells of the myxomycete Didymium iridis accumulate a 7.5-kb RNA that is the result of alternative processing of pre-rRNA. The 5' end corresponds to an internal processing site cleaved by the group I-like ribozyme DiGIR1, located within the twin-ribozyme intron...... context, and presents a new example of the cost to the host of intron load. This is because the formation of the 7.5-kb RNA is incompatible with the formation of functional ribosomal RNA from the same transcript. In the formation of the 7.5-kb RNA, DiGIR1 catalysed cleavage takes place without prior...... splicing performed by DiGIR2. This contrasts with the processing order leading to mature rRNA and I-DirI mRNA in growing cells, suggesting an interplay between the two ribozymes of a twin-ribozyme intron....

  20. A Comparison of the foraging ecology and bioenergetics of the early life-stages of two sympatric hammerhead sharks from 1998-07-12 to 2005-07-27 (NCEI Accession 0163192)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This Archival Information Package (AIP) contains basic biological information on bonnethead and scalloped hammerhead sharks with specific (by stomach and prey item)...

  1. Directional selection causes decanalization in a group I ribozyme.

    Science.gov (United States)

    Hayden, Eric J; Weikert, Christian; Wagner, Andreas

    2012-01-01

    A canalized genotype is robust to environmental or genetic perturbations. Canalization is expected to result from stabilizing selection on a well-adapted phenotype. Decanalization, the loss of robustness, might follow periods of directional selection toward a new optimum. The evolutionary forces causing decanalization are still unknown, in part because it is difficult to determine the fitness effects of mutations in populations of organisms with complex genotypes and phenotypes. Here, we report direct experimental measurements of robustness in a system with a simple genotype and phenotype, the catalytic activity of an RNA enzyme. We find that the robustness of a population of RNA enzymes decreases during a period of directional selection in the laboratory. The decrease in robustness is primarily caused by the selective sweep of a genotype that is decanalized relative to the wild-type, both in terms of mutational robustness and environmental robustness (thermodynamic stability). Our results experimentally demonstrate that directional selection can cause decanalization on short time scales, and demonstrate co-evolution of mutational and environmental robustness.

  2. The life histories of endangered hammerhead sharks (Carcharhiniformes, Sphyrnidae) from the east coast of Australia.

    Science.gov (United States)

    Harry, A V; Macbeth, W G; Gutteridge, A N; Simpfendorfer, C A

    2011-06-01

    The life histories of two globally endangered hammerhead sharks, Sphyrna lewini and Sphyrna mokarran, were examined using samples collected from a range of commercial fisheries operating along the east coast of Australia. The catch of S. lewini was heavily biased towards males, and there were significant differences in von Bertalanffy growth parameters (L(∞) and k) and maturity [stretched total length (L(ST)) and age (A) at which 50% are mature, L(ST50) and A(50)] between those caught in the tropics (L(∞) = 2119 mm, k = 0·163, L(ST50) = 1471 mm, A(50) = 5·7 years) and those caught in temperate waters (L(∞) = 3199 mm, k = 0·093, L(ST50) = 2043 mm, A(50) = 8·9 years). The best-fit estimates for a three-parameter von Bertalanffy growth curve fit to both sexes were L(∞) = 3312 mm, L(0) = 584 mm and k = 0·076. Males attained a maximum age of 21 years and grew to at least 2898 mm L(ST). The longevity, maximum length and maturity of females could not be estimated as mature animals could not be sourced from any fishery. Length at birth inferred from neonates with open umbilical scars was 465-563 mm L(ST). There was no significant difference in length and age at maturity of male and female S. mokarran, which reached 50% maturity at 2279 mm L(ST) and 8·3 years. Sphyrna mokarran grew at a similar rate to S. lewini and the best-fit estimates for a two-parameter von Bertalanffy equation fit to length-at-age data for sexes combined with an assumed mean length-at-birth of 700 mm were L(∞) = 4027 mm and k = 0·079. Females attained a maximum age of 39·1 years and grew to at least 4391 mm L(ST). The oldest male S. mokarran was 31·7 years old and 3691 mm L(ST). Validation of annual growth-band deposition in S. mokarran was achieved through a mark, tag and recapture study. © 2011 The Authors. Journal of Fish Biology © 2011 The Fisheries Society of the British Isles.

  3. Age, growth and maturity of the pelagic thresher Alopias pelagicus and the scalloped hammerhead Sphyrna lewini.

    Science.gov (United States)

    Drew, M; White, W T; Dharmadi; Harry, A V; Huveneers, C

    2015-01-01

    Indonesia has the greatest reported chondrichthyan catches worldwide, with c.110,000 t caught annually. The pelagic thresher (Alopias pelagicus) and scalloped hammerhead (Sphryna lewini) together comprise about 25% of the total catches of sharks landed in Indonesia. Age and growth parameters were estimated for A. pelagicus and S. lewini from growth-band counts of thin-cut vertebral sections. Alopias pelagicus (n = 158) and S. lewini (n = 157) vertebrae were collected from three Indonesian fish markets over a 5 year period. A multi-model analysis was used to estimate growth parameters for both species. The models of best fit for males and females for A. pelagicus was the three-parameter logistic (L∞ = 3169 mm LT , k = 0·2) and the two-parameter von Bertalanffy models (L∞ = 3281 mm LT , k = 0·12). Age at maturity was calculated to be 10·4 and 13·2 years for males and females, respectively, and these are the oldest estimated for this species. The samples of S. lewini were heavily biased towards females, and the model of best fit for males and females was the three-parameter Gompertz (L∞ = 2598 mm LT , k = 0·15) and the two-parameter Gompertz (L∞ = 2896 mm LT , k= 0·16). Age at maturity was calculated to be 8·9 and 13·2 years for males and females, respectively. Although numerous age and growth studies have previously been undertaken on S. lewini, few studies have been able to obtain adequate samples from all components of the population because adult females, adult males and juveniles often reside in different areas. For the first time, sex bias in this study was towards sexually mature females, which are commonly lacking in previous biological studies on S. lewini. Additionally, some of the oldest aged specimens and highest age at maturity for both species were observed in this study. Both species exhibit slow rates of growth and late age at maturity, highlighting the need for a re-assessment of the relative resilience of these two

  4. Extensive use of mesopelagic waters by a Scalloped hammerhead shark (Sphyrna lewini) in the Red Sea

    KAUST Repository

    Spät, Julia L.Y.

    2017-09-06

    Background Despite being frequently landed in fish markets along the Saudi Arabian Red Sea coast, information regarding fundamental biology of the Scalloped hammerhead shark (Sphyrna lewini) in this region is scarce. Satellite telemetry studies can generate important data on life history, describe critical habitats, and ultimately redefine management strategies for sharks. To better understand the horizontal and vertical habitat use of S. lewini in the Red Sea and to aid with potential future development of zoning and management plans for key habitats, we deployed a pop-up satellite archival transmitting tag to track a single female specimen (240 cm total length) for a tracking period of 182 days. Results The tag was physically recovered after a deployment period of 6 months, thus providing the complete archived dataset of more than one million depth and temperature records. Based on a reconstructed, most probable track, the shark travelled a circular distance of approximately 1000 km from the central Saudi Arabian Red Sea southeastward into Sudanese waters, returning to the tagging location toward the end of the tracking period. Mesopelagic excursions to depths between 650 and 971 m occurred on 174 of the 182 days of the tracking period. Intervals between such excursions were characterized by constant oscillatory diving in the upper 100 m of the water column. Conclusions This study provides evidence that mesopelagic habitats might be more commonly used by S. lewini than previously suggested. We identified deep diving behavior throughout the 24-h cycle over the entire 6-month tracking period. In addition to expected nightly vertical habitat use, the shark exhibited frequent mesopelagic excursions during daytime. Deep diving throughout the diel cycle has not been reported before and, while dive functionality remains unconfirmed, our study suggests that mesopelagic excursions may represent foraging events within and below deep scattering layers. Additional research

  5. Evaluation of a Petition Requesting National Marine Fisheries Service (NMFS) to List the Smooth Hammerhead Shark (Sphryna zygaena) as a Threatened or Endangered Species Under the Endangered Species Act (ESA)

    Science.gov (United States)

    Sturm, A. B.

    2016-12-01

    The wildlife conservation organization, Defenders of Wildlife, petitioned NMFS to list the smooth hammerhead shark, Sphryna zygaena, as endangered or threatened throughout its range under the ESA. The petition was critically evaluated to determine if the petitioners presented substantial scientific or commercial information indicating that the smooth hammerhead shark may warrant listing under the ESA. The petition and the cited scientific literature (as well as scientific literature readily available in NMFS files) were evaluated to determine if the smooth hammerhead shark may be threatened or endangered because of any one or a combination of the following five ESA section 4(a)(1) factors: (1) present or threatened destruction, modification, or curtailment of its habitat or range; (2) over utilization for commercial, recreational, scientific, or educational purposes; (3) disease or predation; (4) inadequacy of existing regulatory mechanisms; (5) or other natural or manmade factors affecting its continued existence. The available scientific literature indicates that the smooth hammerhead shark populations have declined in multiple regions. Smooth hammerhead sharks may warrant listing due to ongoing threats of over utilization for commercial purposes by global fisheries that target and retain incidental catch of these species to obtain their high-value fins, possible inadequacies in global regulatory mechanisms to control this level of exploitation, and natural factors (such as inherent biological vulnerabilities) that may be exacerbating these threats. Based on these findings, the smooth hammerhead shark may warrant listing as a threatened or endangered species under the ESA and a status review of the species is currently being conducted.

  6. Contributions to the tooth morphology in early embryos of three species of hammerhead sharks (Elasmobranchii: Sphyrnidae) and their evolutionary implications.

    Science.gov (United States)

    Mello, Waldiney; Brito, Paulo Marques Machado

    2013-09-01

    The tooth types in the embryos of the hammerhead sharks Sphyrna tiburo, Sphyrna tudes and Eusphyra blochii are here described in labial and lingual views, and, in some cases, in additional views. The presence of cusplets was observed in the anterior teeth of S. tiburo and S. tudes, which is secondarily lost after early embryonic stages. Many aligned root foramina were detected in the sphyrnids, which, as the cusplets, are shared by many phylogenetic-related carcharhinids. Other anatomic features, related to the root and central cusp, are presented for the first time. Such characters represent the first step to compare the teeth of extant and fossil species. Copyright © 2013. Published by Elsevier SAS.

  7. Mercury and selenium bioaccumulation in the smooth hammerhead shark, Sphyrna zygaena Linnaeus, from the Mexican Pacific Ocean.

    Science.gov (United States)

    Escobar-Sánchez, O; Galván-Magaña, F; Rosíles-Martínez, R

    2010-04-01

    We analyzed total mercury and selenium bioaccumulation in muscle tissue and cartilage fibers (fins) from smooth hammerhead shark, Sphyrna zygaena, caught off Baja California Sur, Mexico. In muscle tissue, the mercury concentration ranged from 0.005 to 1.93 microg g(-1) ww (wet weight), which falls within the safety limits for food set by international agencies (Hg > 1.0 microg g(-1) ww). Only one specimen showed a mercury value that exceeded this limit. In fins, the mercury bioaccumulation was lower (<0.05). Selenium in muscle ranged from 0.11 to 1.63 microg g(-1) ww, while in fins it ranged from 0.13 to 0.56 microg g(-1) ww.

  8. A computational study of the hydrodynamics in the nasal region of a hammerhead shark (Sphyrna tudes: implications for olfaction.

    Directory of Open Access Journals (Sweden)

    Alex D Rygg

    Full Text Available The hammerhead shark possesses a unique head morphology that is thought to facilitate enhanced olfactory performance. The olfactory chambers, located at the distal ends of the cephalofoil, contain numerous lamellae that increase the surface area for olfaction. Functionally, for the shark to detect chemical stimuli, water-borne odors must reach the olfactory sensory epithelium that lines these lamellae. Thus, odorant transport from the aquatic environment to the sensory epithelium is the first critical step in olfaction. Here we investigate the hydrodynamics of olfaction in Sphyrna tudes based on an anatomically-accurate reconstruction of the head and olfactory chamber from high-resolution micro-CT and MRI scans of a cadaver specimen. Computational fluid dynamics simulations of water flow in the reconstructed model reveal the external and internal hydrodynamics of olfaction during swimming. Computed external flow patterns elucidate the occurrence of flow phenomena that result in high and low pressures at the incurrent and excurrent nostrils, respectively, which induces flow through the olfactory chamber. The major (prenarial nasal groove along the cephalofoil is shown to facilitate sampling of a large spatial extent (i.e., an extended hydrodynamic "reach" by directing oncoming flow towards the incurrent nostril. Further, both the major and minor nasal grooves redirect some flow away from the incurrent nostril, thereby limiting the amount of fluid that enters the olfactory chamber. Internal hydrodynamic flow patterns are also revealed, where we show that flow rates within the sensory channels between olfactory lamellae are passively regulated by the apical gap, which functions as a partial bypass for flow in the olfactory chamber. Consequently, the hammerhead shark appears to utilize external (major and minor nasal grooves and internal (apical gap flow regulation mechanisms to limit water flow between the olfactory lamellae, thus protecting these

  9. Purification, characterization, and biological activity of insulins from the spotted dogfish, Scyliorhinus canicula, and the hammerhead shark, Sphyrna lewini.

    Science.gov (United States)

    Anderson, W Gary; Ali, Mohamed F; Einarsdóttir, Ingibjörg E; Schäffer, Lauge; Hazon, Neil; Conlon, J Michael

    2002-03-01

    Insulin was purified from pancreatic extracts of two elasmobranch species belonging to different families in the order Carcharhiniformes, the European spotted dogfish, Scyliorhinus canicula (Scyliorhinidae), and the hammerhead shark, Sphyrna lewini (Carcharhinidae). The amino acid sequence of dogfish insulin was established as A-chain GIVDHCCRNT(10)CSLYDLEGYC(20)NQ and B-chain LPSQHLCGSH(10)LVETLYFVCG(20)QKGFYYVPKV(30). The primary structure of hammerhead shark insulin was similar to that of dogfish insulin with only 2 amino acid substitutions at A8 (R --> H) and B30 (V --> I). The elasmobranch insulins were markedly different from human insulin (17 amino acid substitutions) but all the residues in human insulin that are believed to be important in determining the receptor binding conformation (B6, B8, B11, B13, B23, B24, B25, A2, A3, and A19) have been conserved in the elasmobranch insulins with the exception of the conservative substitution Phe --> Tyr at B25. Consistent with this, dogfish and human insulin showed almost identical binding affinity to the recombinant solubilized human insulin receptor (K(D) values of 14.0 and 18.6 pM, respectively; relative potency 133%). Previous studies have shown that bovine insulin produces severe and sustained hypoglycemia in elasmobranchs but the effect is of slow onset. Bolus arterial injections of dogfish insulin (10 nmol x kg(-1)) into unanesthetized, fasting dogfish (n = 9) produced no changes in blood glucose, 3-hydroxybutyrate, and acetoacetate concentrations over a 4-h period. In a second series of experiments (n = 7), dogfish insulin (10 nmol x kg(-1)) produced a significant (P < 0.05) fall in blood glucose after 12 h that persisted for at least 48 h, but no change in ketone body concentrations. The data indicate that the metabolic actions of an endogenous elasmobranch insulin in an elasmobranch are similar to those previously described for mammalian insulin.

  10. A computational study of the hydrodynamics in the nasal region of a hammerhead shark (Sphyrna tudes): implications for olfaction.

    Science.gov (United States)

    Rygg, Alex D; Cox, Jonathan P L; Abel, Richard; Webb, Andrew G; Smith, Nadine B; Craven, Brent A

    2013-01-01

    The hammerhead shark possesses a unique head morphology that is thought to facilitate enhanced olfactory performance. The olfactory chambers, located at the distal ends of the cephalofoil, contain numerous lamellae that increase the surface area for olfaction. Functionally, for the shark to detect chemical stimuli, water-borne odors must reach the olfactory sensory epithelium that lines these lamellae. Thus, odorant transport from the aquatic environment to the sensory epithelium is the first critical step in olfaction. Here we investigate the hydrodynamics of olfaction in Sphyrna tudes based on an anatomically-accurate reconstruction of the head and olfactory chamber from high-resolution micro-CT and MRI scans of a cadaver specimen. Computational fluid dynamics simulations of water flow in the reconstructed model reveal the external and internal hydrodynamics of olfaction during swimming. Computed external flow patterns elucidate the occurrence of flow phenomena that result in high and low pressures at the incurrent and excurrent nostrils, respectively, which induces flow through the olfactory chamber. The major (prenarial) nasal groove along the cephalofoil is shown to facilitate sampling of a large spatial extent (i.e., an extended hydrodynamic "reach") by directing oncoming flow towards the incurrent nostril. Further, both the major and minor nasal grooves redirect some flow away from the incurrent nostril, thereby limiting the amount of fluid that enters the olfactory chamber. Internal hydrodynamic flow patterns are also revealed, where we show that flow rates within the sensory channels between olfactory lamellae are passively regulated by the apical gap, which functions as a partial bypass for flow in the olfactory chamber. Consequently, the hammerhead shark appears to utilize external (major and minor nasal grooves) and internal (apical gap) flow regulation mechanisms to limit water flow between the olfactory lamellae, thus protecting these delicate

  11. A Computational Study of the Hydrodynamics in the Nasal Region of a Hammerhead Shark (Sphyrna tudes): Implications for Olfaction

    Science.gov (United States)

    Rygg, Alex D.; Cox, Jonathan P. L.; Abel, Richard; Webb, Andrew G.; Smith, Nadine B.; Craven, Brent A.

    2013-01-01

    The hammerhead shark possesses a unique head morphology that is thought to facilitate enhanced olfactory performance. The olfactory chambers, located at the distal ends of the cephalofoil, contain numerous lamellae that increase the surface area for olfaction. Functionally, for the shark to detect chemical stimuli, water-borne odors must reach the olfactory sensory epithelium that lines these lamellae. Thus, odorant transport from the aquatic environment to the sensory epithelium is the first critical step in olfaction. Here we investigate the hydrodynamics of olfaction in Sphyrna tudes based on an anatomically-accurate reconstruction of the head and olfactory chamber from high-resolution micro-CT and MRI scans of a cadaver specimen. Computational fluid dynamics simulations of water flow in the reconstructed model reveal the external and internal hydrodynamics of olfaction during swimming. Computed external flow patterns elucidate the occurrence of flow phenomena that result in high and low pressures at the incurrent and excurrent nostrils, respectively, which induces flow through the olfactory chamber. The major (prenarial) nasal groove along the cephalofoil is shown to facilitate sampling of a large spatial extent (i.e., an extended hydrodynamic “reach”) by directing oncoming flow towards the incurrent nostril. Further, both the major and minor nasal grooves redirect some flow away from the incurrent nostril, thereby limiting the amount of fluid that enters the olfactory chamber. Internal hydrodynamic flow patterns are also revealed, where we show that flow rates within the sensory channels between olfactory lamellae are passively regulated by the apical gap, which functions as a partial bypass for flow in the olfactory chamber. Consequently, the hammerhead shark appears to utilize external (major and minor nasal grooves) and internal (apical gap) flow regulation mechanisms to limit water flow between the olfactory lamellae, thus protecting these delicate

  12. Comparison of total lipids and fatty acids from liver, heart and abdominal muscle of scalloped (Sphyrna lewini) and smooth (Sphyrna zygaena) hammerhead sharks.

    Science.gov (United States)

    Davidson, Bruce Clement; Nel, Wynand; Rais, Afsha; Namdarizandi, Vahid; Vizarra, Scott; Cliff, Geremy

    2014-01-01

    Liver, heart and abdominal muscle samples from scalloped (Sphyrna lewini) and smooth (Sphyrna zygaena) hammerhead sharks were analysed to characterise their lipid and fatty acid profiles. Samples were compared both between and within species, but there were no significant differences in total lipids for either comparison, although much greater total amounts were found in the liver samples. Within the individual fatty acids, the only significant differences were greater amounts of 22:6n-3, total n-3 polyunsaturates and total polyunsaturates in smooth, when compared to scalloped, hammerhead liver. This may reflect the more wide spread distribution of this species into cooler waters. Within both species the liver levels of the same fatty acid fractions decreased from spring to summer, which may correlate with changes in fatty acid profile to adapt to any differences in amount or species of prey consumed, or other considerations, eg. buoyancy, however there was no data to clarify this.

  13. The electrosensorial pore system of the cephalofoil in the four most common species of hammerhead shark (Elasmobranchii: Sphyrnidae) from the Southwestern Atlantic.

    Science.gov (United States)

    Mello, Waldiney

    2009-04-01

    The laterally expanded head is the principal character distinguishing hammerhead sharks, and its morphology is important for interpreting their ontogeny and species diversity. Because their head shape changes during its ontogeny, it is vital to evaluate it in order to establish other taxonomical characteristics to correctly identify Sphyrna species. This study examines the distribution of electrosensorial pore regions on the ventral surface of the cephalofoil (VSC) in Sphyrna lewini, S. tiburo, S. tudes and S. zygaena from the Southwestern Atlantic Ocean. The pore distribution patterns in the VSC can distinguish these species. Use of those patterns, with the head shape, confirms the identification of the four most common species of hammerhead sharks in the Southwestern Atlantic.

  14. SOME BIOLOGICAL ASPECTS OF SCALLOPED HAMMERHEAD SHARKS (Sphyrna lewini Griffith & Smith, 1834) CAUGHT FROM COASTAL FISHERIES IN THE EASTERN INDIAN OCEAN

    OpenAIRE

    Umi Chodrijah; Bram Setyadji

    2015-01-01

    Indonesia has the largest chondrichthyan fishery in the world, with a reported of 105,000 and 118,000 tonnes landed in 2002 and 2003 respectively. Scalloped hammerhead shark was either targeted or by-catch from this fishery, mostly for its fins. Despite of the growing concern around the world, the availability of biological data of this species, especially in the Eastern Indian Ocean is still lacking. The objectives of this paper are to present some biological information (size composition an...

  15. Thirty-five years of research into ribozymes and nucleic acid catalysis: where do we stand today? [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Sabine Müller

    2016-06-01

    Full Text Available Since the discovery of the first catalytic RNA in 1981, the field of ribozyme research has developed from the discovery of catalytic RNA motifs in nature and the elucidation of their structures and catalytic mechanisms, into a field of engineering and design towards application in diagnostics, molecular biology and medicine. Owing to the development of powerful protocols for selection of nucleic acid catalysts with a desired functionality from random libraries, the spectrum of nucleic acid supported reactions has greatly enlarged, and importantly, ribozymes have been accompanied by DNAzymes. Current areas of research are the engineering of allosteric ribozymes for artificial regulation of gene expression, the design of ribozymes and DNAzymes for medicinal and environmental diagnostics, and the demonstration of RNA world relevant ribozyme activities. In addition, new catalytic motifs or novel genomic locations of known motifs continue to be discovered in all branches of life by the help of high-throughput bioinformatic approaches. Understanding the biological role of the catalytic RNA motifs widely distributed in diverse genetic contexts belongs to the big challenges of future RNA research.

  16. Simple peptides derived from the ribosomal core potentiate RNA polymerase ribozyme function

    Science.gov (United States)

    Tagami, Shunsuke; Attwater, James; Holliger, Philipp

    2017-04-01

    The emergence of functional interactions between nucleic acids and polypeptides was a key transition in the origin of life and remains at the heart of all biology. However, how and why simple non-coded peptides could have become critical for RNA function is unclear. Here, we show that putative ancient peptide segments from the cores of both ribosomal subunits enhance RNA polymerase ribozyme (RPR) function, as do derived homopolymeric peptides comprising lysine or the non-proteinogenic lysine analogues ornithine or, to a lesser extent, diaminobutyric acid, irrespective of chirality or chiral purity. Lysine decapeptides enhance RPR function by promoting holoenzyme assembly through primer-template docking, accelerate RPR evolution, and allow RPR-catalysed RNA synthesis at near physiological (≥1 mM) Mg2+ concentrations, enabling templated RNA synthesis within membranous protocells. Our results outline how compositionally simple, mixed-chirality peptides may have augmented the functional potential of early RNAs and promoted the emergence of the first protocells.

  17. Phase 2 gene therapy trial of an anti-HIV ribozyme in autologous CD34+ cells.

    Science.gov (United States)

    Mitsuyasu, Ronald T; Merigan, Thomas C; Carr, Andrew; Zack, Jerome A; Winters, Mark A; Workman, Cassy; Bloch, Mark; Lalezari, Jacob; Becker, Stephen; Thornton, Lorna; Akil, Bisher; Khanlou, Homayoon; Finlayson, Robert; McFarlane, Robert; Smith, Don E; Garsia, Roger; Ma, David; Law, Matthew; Murray, John M; von Kalle, Christof; Ely, Julie A; Patino, Sharon M; Knop, Alison E; Wong, Philip; Todd, Alison V; Haughton, Margaret; Fuery, Caroline; Macpherson, Janet L; Symonds, Geoff P; Evans, Louise A; Pond, Susan M; Cooper, David A

    2009-03-01

    Gene transfer has potential as a once-only treatment that reduces viral load, preserves the immune system and avoids lifetime highly active antiretroviral therapy. This study, which is to our knowledge the first randomized, double-blind, placebo-controlled, phase 2 cell-delivered gene transfer clinical trial, was conducted in 74 HIV-1-infected adults who received a tat-vpr-specific anti-HIV ribozyme (OZ1) or placebo delivered in autologous CD34+ hematopoietic progenitor cells. There were no OZ1-related adverse events. There was no statistically significant difference in viral load between the OZ1 and placebo group at the primary end point (average at weeks 47 and 48), but time-weighted areas under the curve from weeks 40-48 and 40-100 were significantly lower in the OZ1 group. Throughout the 100 weeks, CD4+ lymphocyte counts were higher in the OZ1 group. This study indicates that cell-delivered gene transfer is safe and biologically active in individuals with HIV and can be developed as a conventional therapeutic product.

  18. Robust Sub-harmonic Mixer at 340 GHz Using Intrinsic Resonances of Hammer-Head Filter and Improved Diode Model

    Science.gov (United States)

    Wang, Cheng; He, Yue; Lu, Bin; Jiang, Jun; Miao, Li; Deng, Xian-Jin; Xiong, Yong-zhong; Zhang, Jian

    2017-11-01

    This paper presents a sub-harmonic mixer at 340 GHz based on anti-parallel Schottky diodes (SBDs). Intrinsic resonances in low-pass hammer-head filter have been adopted to enhance the isolation for different harmonic components, while greatly minimizing the transmission loss. The application of new DC grounding structure, impedance matching structure, and suspended micro-strip mitigates the negative influences of fabrication errors from metal cavity, quartz substrate, and micro-assembly. An improved lumped element equivalent circuit model of SBDs guarantees the accuracy of simulation, which takes current-voltage (I/V) behavior, capacitance-voltage (C/V) behavior, carrier velocity saturation, DC series resistor, plasma resonance, skin effect, and four kinds of noise generation mechanisms into consideration thoroughly. The measurement indicates that with local oscillating signal of 2 mW, the lowest double sideband conversion loss is 5.5 dB at 339 GHz; the corresponding DSB noise temperature is 757 K. The 3 dB bandwidth of conversion loss is 50 GHz from 317 to 367 GHz.

  19. Complexity

    Indian Academy of Sciences (India)

    Rahul Pandit

    2008-10-31

    Oct 31, 2008 ... ”The more complex a thing is, the more you can talk about it.” - attributed to Giorgio Parisi. ▻ ”C'est magnifique, mais ce n'est pas de la science.” (It is magnificent, but not all of it is science.) - attributed ... Earliest examples: theoretical computer science, algorithmic complexity, etc. ▻ Rapid progress after the ...

  20. In-line alignment and Mg²⁺ coordination at the cleavage site of the env22 twister ribozyme.

    Science.gov (United States)

    Ren, Aiming; Košutić, Marija; Rajashankar, Kanagalaghatta R; Frener, Marina; Santner, Tobias; Westhof, Eric; Micura, Ronald; Patel, Dinshaw J

    2014-11-20

    Small self-cleaving nucleolytic ribozymes contain catalytic domains that accelerate site-specific cleavage/ligation of phosphodiester backbones. We report on the 2.9-Å crystal structure of the env22 twister ribozyme, which adopts a compact tertiary fold stabilized by co-helical stacking, double-pseudoknot formation and long-range pairing interactions. The U-A cleavage site adopts a splayed-apart conformation with the modelled 2'-O of U positioned for in-line attack on the adjacent to-be-cleaved P-O5' bond. Both an invariant guanosine and a Mg(2+) are directly coordinated to the non-bridging phosphate oxygens at the U-A cleavage step, with the former positioned to contribute to catalysis and the latter to structural integrity. The impact of key mutations on cleavage activity identified an invariant guanosine that contributes to catalysis. Our structure of the in-line aligned env22 twister ribozyme is compared with two recently reported twister ribozymes structures, which adopt similar global folds, but differ in conformational features around the cleavage site.

  1. Feeding strategy of the night shark (Carcharhinus signatus and scalloped hammerhead shark (Sphyrna lewini near seamounts off northeastern Brazil

    Directory of Open Access Journals (Sweden)

    Teodoro Vaske Júnior

    2009-06-01

    Full Text Available A total of 425 stomachs of night shark (Carcharhinus signatus, and 98 stomachs of scalloped hammerhead shark (Sphyrna lewini, from longline and surface gillneters near seamounts off northeastern Brazil, were analysed between 1992 and 1999. Both predators prey upon reef and benthopelagic fishes, migrant cephalopods and deep water crustaceans, showing similar feeding niches (Schoener Index T=0.75. The great prey richness of the diets may reflect the fact that the marine food web for these species is very extensive in this region. Due to the concentration for feeding of both predators in the seamounts, intense fisheries should be monitored to avoid localised depletions.Um total de 425 estômagos de tubarão-toninha (Carcharhinus signatus e 98 estômagos de tubarão-martelo-entalhado (Sphyrna lewini, oriundos da pesca de espinhel e pesca com rede de emalhe nas adjacências dos bancos oceânicos do nordeste do Brasil, foi analisado entre 1992 e 1999. Ambas as espécies predam sobre peixes bento-pelágicos e recifais, cefalópodes migradores, e crustáceos de águas profundas, apresentando nichos alimentares similares (Índice de Schoener T=0.75. A alta riqueza de presas nas dietas deve ser um reflexo de que as teias alimentares para estas espécies são consideravelmente longas nessa região. Devido à concentração alimentar de ambos predadores nos bancos oceânicos, a pescaria intensa deve ser monitorada para evitar depleções locais.

  2. Global phylogeography with mixed-marker analysis reveals male-mediated dispersal in the endangered scalloped hammerhead shark (Sphyrna lewini).

    Science.gov (United States)

    Daly-Engel, Toby S; Seraphin, Kanesa D; Holland, Kim N; Coffey, John P; Nance, Holly A; Toonen, Robert J; Bowen, Brian W

    2012-01-01

    The scalloped hammerhead shark, Sphyrna lewini, is a large endangered predator with a circumglobal distribution, observed in the open ocean but linked ontogenetically to coastal embayments for parturition and juvenile development. A previous survey of maternal (mtDNA) markers demonstrated strong genetic partitioning overall (global Φ(ST) = 0.749) and significant population separations across oceans and between discontinuous continental coastlines. We surveyed the same global range with increased sample coverage (N = 403) and 13 microsatellite loci to assess the male contribution to dispersal and population structure. Biparentally inherited microsatellites reveal low or absent genetic structure across ocean basins and global genetic differentiation (F(ST) = 0.035) over an order of magnitude lower than the corresponding measures for maternal mtDNA lineages (Φ(ST) = 0.749). Nuclear allelic richness and heterozygosity are high throughout the Indo-Pacific, while genetic structure is low. In contrast, allelic diversity is low while population structure is higher for populations at the ends of the range in the West Atlantic and East Pacific. These data are consistent with the proposed Indo-Pacific center of origin for S. lewini, and indicate that females are philopatric or adhere to coastal habitats while males facilitate gene flow across oceanic expanses. This study includes the largest sampling effort and the most molecular loci ever used to survey the complete range of a large oceanic predator, and findings emphasize the importance of incorporating mixed-marker analysis into stock assessments of threatened and endangered shark species.

  3. Global phylogeography with mixed-marker analysis reveals male-mediated dispersal in the endangered scalloped hammerhead shark (Sphyrna lewini.

    Directory of Open Access Journals (Sweden)

    Toby S Daly-Engel

    Full Text Available The scalloped hammerhead shark, Sphyrna lewini, is a large endangered predator with a circumglobal distribution, observed in the open ocean but linked ontogenetically to coastal embayments for parturition and juvenile development. A previous survey of maternal (mtDNA markers demonstrated strong genetic partitioning overall (global Φ(ST = 0.749 and significant population separations across oceans and between discontinuous continental coastlines.We surveyed the same global range with increased sample coverage (N = 403 and 13 microsatellite loci to assess the male contribution to dispersal and population structure. Biparentally inherited microsatellites reveal low or absent genetic structure across ocean basins and global genetic differentiation (F(ST = 0.035 over an order of magnitude lower than the corresponding measures for maternal mtDNA lineages (Φ(ST = 0.749. Nuclear allelic richness and heterozygosity are high throughout the Indo-Pacific, while genetic structure is low. In contrast, allelic diversity is low while population structure is higher for populations at the ends of the range in the West Atlantic and East Pacific.These data are consistent with the proposed Indo-Pacific center of origin for S. lewini, and indicate that females are philopatric or adhere to coastal habitats while males facilitate gene flow across oceanic expanses. This study includes the largest sampling effort and the most molecular loci ever used to survey the complete range of a large oceanic predator, and findings emphasize the importance of incorporating mixed-marker analysis into stock assessments of threatened and endangered shark species.

  4. Molecular Dynamics Study of Twister Ribozyme: Role of Mg(2+) Ions and the Hydrogen-Bonding Network in the Active Site.

    Science.gov (United States)

    Ucisik, Melek N; Bevilacqua, Philip C; Hammes-Schiffer, Sharon

    2016-07-12

    The recently discovered twister ribozyme is thought to utilize general acid-base catalysis in its self-cleavage mechanism, but the roles of nucleobases and metal ions in the mechanism are unclear. Herein, molecular dynamics simulations of the env22 twister ribozyme are performed to elucidate the structural and equilibrium dynamical properties, as well as to examine the role of Mg(2+) ions and possible candidates for the general base and acid in the self-cleavage mechanism. The active site region and the ends of the pseudoknots were found to be less mobile than other regions of the ribozyme, most likely providing structural stability and possibly facilitating catalysis. A purported catalytic Mg(2+) ion and the closest neighboring Mg(2+) ion remained chelated and relatively immobile throughout the microsecond trajectories, although removal of these Mg(2+) ions did not lead to any significant changes in the structure or equilibrium motions of the ribozyme on the microsecond time scale. In addition, a third metal ion, a Na(+) ion remained close to A1(O5'), the leaving group atom, during the majority of the microsecond trajectories, suggesting that it might stabilize the negative charge on A1(O5') during self-cleavage. The locations of these cations and their interactions with key nucleotides in the active site suggest that they may be catalytically relevant. The P1 stem is partially melted at its top and bottom in the crystal structure and further unwinds in the trajectories. The simulations also revealed an interconnected network comprised of hydrogen-bonding and π-stacking interactions that create a relatively rigid network around the self-cleavage site. The nucleotides involved in this network are among the highly conserved nucleotides in twister ribozymes, suggesting that this interaction network may be important to structure and function.

  5. Molecular and pathological characterization of Fusarium solani species complex infection in the head and lateral line system of Sphyrna lewini.

    Science.gov (United States)

    Pirarat, Nopadon; Sahatrakul, Komsil; Lacharoje, Sitthichok; Lombardini, Eric; Chansue, Nantarika; Techangamsuwan, Somporn

    2016-08-09

    A severe fungal infection affecting the head and lateral line system was diagnosed in 7 captive scalloped hammerhead sharks Sphyrna lewini in an aquarium in Thailand. Extensive and severe necrotizing cellulitis was consistently observed microscopically along the cephalic and lateral line canals in conjunction with positive fungal cultures for Fusarium sp. Molecular phylogenetic analysis was performed from 3 isolates based on the nucleotide sequences containing internally transcribed spacer (ITS) and a portion of 5.8S and 28S rDNA. The fungus was highly homologous (100%) and closely related to F. solani species complex 2 (FSSC 2), which belongs to Clade 3 of the FSSC. Our results illustrate the histopathological findings and expand upon our knowledge of the prevalence of invasive fusariosis in the head and lateral line system of hammerhead sharks.

  6. Synthesis of a bifunctional cytidine derivative and its conjugation to RNA for in vitro selection of a cytidine deaminase ribozyme

    Directory of Open Access Journals (Sweden)

    Nico Rublack

    2014-08-01

    Full Text Available Over the past 20 years, the generation of functional RNAs by in vitro selection has become a standard technique. Apart from aptamers for simple binding of defined ligands, also RNAs for catalysis of chemical reactions have been selected. In the latter case, a key step often is the conjugation of one of the two reactants to the library, requiring suitable strategies for terminal or internal RNA functionalization. With the aim of selecting a ribozyme for deamination of cytidine, we have set up a selection scheme involving the attachment of the cytidine acting as deamination substrate to the 3'-terminus of the RNAs in the library, and library immobilization. Here, we report the synthesis of a bifunctional cytidine derivative suitable for conjugation to RNA and linkage of the conjugated library to a streptavidine-coated surface. Successful conjugation of the cytidine derivative to the 3'-terminus of a model RNA is demonstrated.

  7. Extensive Molecular Dynamics Simulations Show That Canonical G8 and Protonated A38H+ Forms Are Most Consistent with Crystal Structures of Hairpin Ribozyme

    Science.gov (United States)

    Mlýnský, Vojtěch; Banáš, Pavel; Hollas, Daniel; Réblová, Kamila; Walter, Nils G.; Šponer, Jiří; Otyepka, Michal

    2010-01-01

    The hairpin ribozyme is a prominent member of the group of small catalytic RNAs (RNA enzymes or ribozymes) because it does not require metal ions to achieve catalysis. Biochemical and structural data have implicated guanine 8 (G8) and adenine 38 (A38) as catalytic participants in cleavage and ligation catalyzed by the hairpin ribozyme, yet their exact role in catalysis remains disputed. To gain insight into dynamics in the active site of a minimal self-cleaving hairpin ribozyme, we have performed extensive classical, explicit-solvent molecular dynamics (MD) simulations on timescales of 50-150 ns. Starting from the available X-ray crystal structures, we investigated the structural impact of the protonation states of G8 and A38, and the inactivating A−1(2′-methoxy) substitution employed in crystallography. Our simulations reveal that a canonical G8 agrees well with the crystal structures while a deprotonated G8 profoundly distorts the active site. Thus MD simulations do not support a straightforward participation of the deprotonated G8 in catalysis. By comparison, the G8 enol tautomer is structurally well tolerated, causing only local rearrangements in the active site. Furthermore, a protonated A38H+ is more consistent with the crystallography data than a canonical A38. The simulations thus support the notion that A38H+ is the dominant form in the crystals, grown at pH 6. In most simulations, the canonical A38 departs from the scissile phosphate and substantially perturbs the structures of active site and S-turn. Yet, we occasionally also observe formation of a stable A−1(2′-OH)…A38(N1) hydrogen bond, which documents the ability of the ribozyme to form this hydrogen bond, consistent with a potential role of A38 as general base catalyst. The presence of this hydrogen bond is, however, incompatible with the expected in-line attack angle necessary for self-cleavage, requiring a rapid transition of the deprotonated 2′-oxyanion to a position more favorable for

  8. Extensive molecular dynamics simulations showing that canonical G8 and protonated A38H+ forms are most consistent with crystal structures of hairpin ribozyme.

    Science.gov (United States)

    Mlýnský, Vojtech; Banás, Pavel; Hollas, Daniel; Réblová, Kamila; Walter, Nils G; Sponer, Jirí; Otyepka, Michal

    2010-05-20

    The hairpin ribozyme is a prominent member of the group of small catalytic RNAs (RNA enzymes or ribozymes) because it does not require metal ions to achieve catalysis. Biochemical and structural data have implicated guanine 8 (G8) and adenine 38 (A38) as catalytic participants in cleavage and ligation catalyzed by the hairpin ribozyme, yet their exact role in catalysis remains disputed. To gain insight into dynamics in the active site of a minimal self-cleaving hairpin ribozyme, we have performed extensive classical, explicit-solvent molecular dynamics (MD) simulations on time scales of 50-150 ns. Starting from the available X-ray crystal structures, we investigated the structural impact of the protonation states of G8 and A38, and the inactivating A-1(2'-methoxy) substitution employed in crystallography. Our simulations reveal that a canonical G8 agrees well with the crystal structures while a deprotonated G8 profoundly distorts the active site. Thus MD simulations do not support a straightforward participation of the deprotonated G8 in catalysis. By comparison, the G8 enol tautomer is structurally well tolerated, causing only local rearrangements in the active site. Furthermore, a protonated A38H(+) is more consistent with the crystallography data than a canonical A38. The simulations thus support the notion that A38H(+) is the dominant form in the crystals, grown at pH 6. In most simulations, the canonical A38 departs from the scissile phosphate and substantially perturbs the structures of the active site and S-turn. Yet, we occasionally also observe formation of a stable A-1(2'-OH)...A38(N1) hydrogen bond, which documents the ability of the ribozyme to form this hydrogen bond, consistent with a potential role of A38 as general base catalyst. The presence of this hydrogen bond is, however, incompatible with the expected in-line attack angle necessary for self-cleavage, requiring a rapid transition of the deprotonated 2'-oxyanion to a position more favorable for

  9. Predominance of genetic monogamy by females in a hammerhead shark, Sphyrna tiburo: implications for shark conservation.

    Science.gov (United States)

    Chapman, Demian D; Prodöhl, Paulo A; Gelsleichter, James; Manire, Charles A; Shivji, Mahmood S

    2004-07-01

    There is growing interest in the mating systems of sharks and their relatives (Class Chondrichthyes) because these ancient fishes occupy a key position in vertebrate phylogeny and are increasingly in need of conservation due to widespread overexploitation. Based on precious few genetic and field observational studies, current speculation is that polyandrous mating strategies and multiple paternity may be common in sharks as they are in most other vertebrates. Here, we test this hypothesis by examining the genetic mating system of the bonnethead shark, Sphyrna tiburo, using microsatellite DNA profiling of 22 litters (22 mothers, 188 embryos genotyped at four polymorphic loci) obtained from multiple locations along the west coast of Florida. Contrary to expectations based on the ability of female S. tiburo to store sperm, the social nature of this species and the 100% multiple paternity observed in two other coastal shark species, over 81% of sampled bonnethead females produced litters sired by a single male (i.e. genetic monogamy). When multiple paternity occurred in S. tiburo, there was an indication of increased incidence in larger mothers with bigger litters. Our data suggest that sharks may exhibit complex genetic mating systems with a high degree of interspecific variability, and as a result some species may be more susceptible to loss of genetic variation in the face of escalating fishing pressure. Based on these findings, we suggest that knowledge of elasmobranch mating systems should be an important component of conservation and management programmes for these heavily exploited species.

  10. A conformational switch in the DiGIR1 ribozyme involved in release and folding of the downstream I-DirI mRNA

    DEFF Research Database (Denmark)

    Nielsen, Henrik; Einvik, Christer; Lentz, Thomas E

    2009-01-01

    DiGIR1 is a group I-like cleavage ribozyme found as a structural domain within a nuclear twin-ribozyme group I intron. DiGIR1 catalyzes cleavage by branching at an Internal Processing Site (IPS) leading to formation of a lariat cap at the 5'-end of the 3'-cleavage product. The 3'-cleavage product...... reaction, thus giving it directionality. Furthermore, the release of the mRNA is a consequence of branching rather than hydrolytic cleavage. A model is put forward that explains the release of the I-DirI mRNA with a lariat cap and a structured 5'-UTR as a direct consequence of the DiGIR1 branching reaction...

  11. A new species of Phoreiobothrium (Cestoidea:Tetraphyllidea) from the great hammerhead shark Sphyrna mokarran and its implications for the evolution of the onchobothriid scolex.

    Science.gov (United States)

    Caira, J N; Healy, C J; Swanson, J

    1996-06-01

    Phoreiobothrium manirei n. sp. is described from the spiral intestines of 3 immature individuals of the great hammerhead shark Sphyrna mokarran collected off of the west coast of Florida. This cestode is unusual in that it possesses 4 muscular papillae on the anterior margin of the accessory sucker. Numerous small protrusions with central cilium-like projections were conspicuous throughout the posterior margin of each bothridium. This species possesses the unique combination of bothridia posteriorly subdivided into subloculi and hooks with extended bases and 2 rather than 3 prongs. In fact, the hooks are strikingly like those of species in the genera Dicranobothrium and Platybothrium. This combination of characters suggests that the bifid hook condition is plesiomorphic with respect to the trifid hook condition within the Onchobothriidae. These data further suggest that the triloculated bothridial condition is plesiomorphic relative to the biloculated condition.

  12. A Conserved Target Site in HIV-1 Gag RNA is Accessible to Inhibition by Both an HDV Ribozyme and a Short Hairpin RNA

    Directory of Open Access Journals (Sweden)

    Robert J Scarborough

    2014-01-01

    Full Text Available Antisense-based molecules targeting HIV-1 RNA have the potential to be used as part of gene or drug therapy to treat HIV-1 infection. In this study, HIV-1 RNA was screened to identify more conserved and accessible target sites for ribozymes based on the hepatitis delta virus motif. Using a quantitative screen for effects on HIV-1 production, we identified a ribozyme targeting a highly conserved site in the Gag coding sequence with improved inhibitory potential compared to our previously described candidates targeting the overlapping Tat/Rev coding sequence. We also demonstrate that this target site is highly accessible to short hairpin directed RNA interference, suggesting that it may be available for the binding of antisense RNAs with different modes of action. We provide evidence that this target site is structurally conserved in diverse viral strains and that it is sufficiently different from the human transcriptome to limit off-target effects from antisense therapies. We also show that the modified hepatitis delta virus ribozyme is more sensitive to a mismatch in its target site compared to the short hairpin RNA. Overall, our results validate the potential of a new target site in HIV-1 RNA to be used for the development of antisense therapies.

  13. Tumor-specific expression of anti-mdr1 ribozyme selectively restores chemosensitivity in multidrug-resistant colon-adenocarcinoma cells.

    Science.gov (United States)

    Gao, Z; Gao, Z; Fields, J Z; Boman, B M

    1999-07-30

    P-glycoprotein (Pgp)-conferred multidrug resistance (MDR) is expressed in cancer and in normal colon tissues and has important physiological functions. In order to selectively reverse MDR in malignant tissue without disrupting the function of normal colonocytes, a retroviral vector (pCEAMR) containing anti-mdr1 ribozyme coupled to the carcino-embryonic-antigen (CEA) promoter was constructed and introduced into resistant colon-cancer cells (SW1116R) that produce CEA and into control resistant cells (HeLaK) that do not produce CEA. Anti-mdr1 ribozyme was expressed in SW1116R cells but not in HeLaK cells. Subsequently, the expression of mdr1 mRNA and Pgp decreased significantly in the transfected SW1116R cells, and was even lower than in parent non-resistant SW1116 cells. The functional ability of Pgp to facilitate rhodamine 123 (Rh123) efflux showed that the transfected SW1116R cells with low Pgp expression retained Rh123, whereas non-transfected SW1116R cells with high Pgp expression released the dye quickly. There was no difference in mdr1 mRNA or in Pgp between non-transfected and transfected HeLaK cells. Drug resistance to doxorubicin (DOX) decreased 93.1% in the transfected SW1116R cells, while no change in drug resistance occurred in the infected HeLaK cells. DOX could clearly inhibit the growth of transfected SW1116R tumors but had no effect on untransfected and on transfected HeLaK cells in vivo. These results indicate that our anti-mdr1 ribozyme is expressed only in CEA-producing colon-cancer cells and reverses their drug resistance selectively.

  14. Reduction of stromal fibroblast-induced mammary tumor growth, by retroviral ribozyme transgenes to hepatocyte growth factor/scatter factor and its receptor, c-MET.

    Science.gov (United States)

    Jiang, Wen G; Grimshaw, David; Martin, Tracey A; Davies, Gaynor; Parr, Christian; Watkins, Gareth; Lane, Jane; Abounader, Roger; Laterra, John; Mansel, Robert E

    2003-09-15

    Hepatocyte growth factor/scatter factor (HGF/SF) is known to increase the invasiveness and migration of cancer cells in vitro and induce angiogenesis. This study examined if inhibition of HGF/SF receptor expression by cancer cells and HGF/SF expression by stromal fibroblasts affects the growth of mammary cancer. Transgenes encoding ribozymes to specifically target human HGF/SF receptor (pLXSN-MET) or HGF/SF (pLXSN-HGF) were constructed using a pLXSN retroviral vector. Human mammary cancer cells MDA MB 231 was transduced with pLXSN-MET (MDA(+/+)). A human fibroblast cell line MRC5, which produces bioactive HGF/SF, was transduced with pLXSN-HGF (MRC5(+/+)). These cells were used in a nude mice breast tumor model. HGF receptor in MDA(+/+) cells and HGF in MRC5(+/+)cells were successfully removed with respective ribozymes as shown by reverse transcription-PCR and Western blotting, respectively. MDA(+/+) was found to have reduced invasiveness when stimulated with HGF/SF. MRC5(+/+) exhibited a significant reduction in HGF/SF production. When injected into athymic nude mice, MDA(+/+) exhibited a slower rate of growth, compared with the wild type (MDA(-/-)), and the cells transduced with control viral vector (MDA(+/-)). The growth of MDA(-/-) tumor was significantly enhanced when coimplanted with wild-type MRC5 (MRC5(-/-)), and the stimulatory effect was reduced when MRC5(+/+) cells were coimplanted instead of MRC5(-/-). The reduction of tumor growth was accompanied by reduction of angiogenesis, as demonstrated by the staining of VE-cadherin in primary tumor tissues. Retroviral ribozyme transgenes targeting HGF/SF in fibroblasts or its receptor cMET in mammary cancer cells can reduce the growth of mammary cancer and associated angiogenesis by inhibiting paracrine stromal-tumor cell interactions.

  15. General base catalysis for cleavage by the active-site cytosine of the hepatitis delta virus ribozyme: QM/MM calculations establish chemical feasibility

    Czech Academy of Sciences Publication Activity Database

    Banáš, Pavel; Rulíšek, Lubomír; Hánošová, V.; Svozil, Daniel; Walter, N.G.; Šponer, Jiří; Otyepka, Michal

    2008-01-01

    Roč. 112, č. 35 (2008), s. 11177-11187 ISSN 1520-6106 R&D Projects: GA MŠk LC512; GA MŠk(CZ) LC06030; GA AV ČR(CZ) IAA400040802; GA AV ČR 1QS500040581 Grant - others:NIH(US) GM62357 Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : HDV ribozyme * catalysis * QM/MM calculations Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 4.189, year: 2008

  16. A ribozyme transcribed by a ribozyme

    DEFF Research Database (Denmark)

    Bentin, Thomas

    2011-01-01

    Prominent current ideas on how life emerged on Earth include an RNA world hypothesis in which RNA performed informational as well as catalytic functions in the absence of both DNA and protein. Demonstration of a self-replicative system based on ribonucleic acid polymers as both information carrie...

  17. Tachykinins with unusual structural features from a urodele, the amphiuma, an elasmobranch, the hammerhead shark, and an agnathan, the river lamprey.

    Science.gov (United States)

    Waugh, D; Bondareva, V; Rusakov, Y; Bjenning, C; Nielsen, P F; Conlon, J M

    1995-01-01

    Tachykinins were purified from extracts of gastrointestinal tissues of the urodele, Amphiuma tridactylum (three-toed amphiuma), and the elasmobranch Sphyrna lewini (hammerhead shark), and from the brain of the agnathan Lampetra fluviatilis (river lamprey). The amphiuma substance P (SP) (DNPSVGQFYGLM-NH2) contains 12 amino residues compared with 11 for mammalian SP and lacks the Arg/Lys-Pro-Xaa-Pro motif that is characteristic of NK1 receptor-selective agonists. Lampetra SP (RKPHPKEFVGLM-NH2) is identical to SP from the sea lamprey and the shark SP-related peptide (AKFDKFYGLM-NH2) is identical to dogfish scyliorhinin I. Amphiuma neurokinin A (NKA) (HKDAFIGLM-NH2) and lamprey NKA (HFDEFVGLM-NH2) contain 9 amino acid residues compared with 10 for mammalian NKA. The shark NKA-related peptide (ASGPTQAGIV10GRKRQKGEMF20VGLM-NH2) shows limited structural similarity to mammalian neuropeptide gamma and the teleost tachykinin, carassin but contains 24 rather than 21 amino acid residues. The data show that the primary structures of the tachykinins have been very poorly conserved during vertebrate evolution and that pressure has acted only to maintain the functionally important sequence -Phe-Xaa-Gly Leu-Met-NH2 at the COOH-termini of the peptides.

  18. How the discovery of ribozymes cast RNA in the roles of both chicken and egg in origin-of-life theories.

    Science.gov (United States)

    Sankaran, Neeraja

    2012-12-01

    Scientific theories about the origin-of-life theories have historically been characterized by the chicken-and-egg problem of which essential aspect of life was the first to appear, replication or self-sustenance. By the 1950s the question was cast in molecular terms and DNA and proteins had come to represent the carriers of the two functions. Meanwhile, RNA, the other nucleic acid, had played a capricious role in origin theories. Because it contained building blocks very similar to DNA, biologists recognized early that RNA could store information in its linear sequences. With the discovery in the 1980s that RNA molecules were capable of biological catalysis, a function hitherto ascribed to proteins alone, RNA took on the role of the single entity that could act as both chicken and egg. Within a few years of the discovery of these catalytic RNAs (ribozymes) scientists had formulated an RNA World hypothesis that posited an early phase in the evolution of life where all key functions were performed by RNA molecules. This paper traces the history the role of RNA in origin-of-life theories with a focus on how the discovery of ribozymes influenced the discourse. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. A modern mode of activation for nucleic acid enzymes.

    Directory of Open Access Journals (Sweden)

    Dominique Lévesque

    2007-07-01

    Full Text Available Through evolution, enzymes have developed subtle modes of activation in order to ensure the sufficiently high substrate specificity required by modern cellular metabolism. One of these modes is the use of a target-dependent module (i.e. a docking domain such as those found in signalling kinases. Upon the binding of the target to a docking domain, the substrate is positioned within the catalytic site. The prodomain acts as a target-dependent module switching the kinase from an off state to an on state. As compared to the allosteric mode of activation, there is no need for the presence of a third partner. None of the ribozymes discovered to date have such a mode of activation, nor does any other known RNA. Starting from a specific on/off adaptor for the hepatitis delta virus ribozyme, that differs but has a mechanism reminiscent of this signalling kinase, we have adapted this mode of activation, using the techniques of molecular engineering, to both catalytic RNAs and DNAs exhibiting various activities. Specifically, we adapted three cleaving ribozymes (hepatitis delta virus, hammerhead and hairpin ribozymes, a cleaving 10-23 deoxyribozyme, a ligating hairpin ribozyme and an artificially selected capping ribozyme. In each case, there was a significant gain in terms of substrate specificity. Even if this mode of control is unreported for natural catalytic nucleic acids, its use needs not be limited to proteinous enzymes. We suggest that the complexity of the modern cellular metabolism might have been an important selective pressure in this evolutionary process.

  20. Characterization of cis-Acting RNA Elements of Zika Virus by Using a Self-Splicing Ribozyme-Dependent Infectious Clone.

    Science.gov (United States)

    Liu, Zhong-Yu; Yu, Jiu-Yang; Huang, Xing-Yao; Fan, Hang; Li, Xiao-Feng; Deng, Yong-Qiang; Ji, Xue; Cheng, Meng-Li; Ye, Qing; Zhao, Hui; Han, Jian-Feng; An, Xiao-Ping; Jiang, Tao; Zhang, Bo; Tong, Yi-Gang; Qin, Cheng-Feng

    2017-11-01

    Zika virus (ZIKV) has caused significant outbreaks and epidemics in the Americas recently, raising global concern due to its ability to cause microcephaly and other neurological complications. A stable and efficient infectious clone of ZIKV is urgently needed. However, the instability and toxicity of flavivirus cDNA clones in Escherichia coli hosts has hindered the development of ZIKV infectious clones. Here, using a novel self-splicing ribozyme-based strategy, we generated a stable infectious cDNA clone of a contemporary ZIKV strain imported from Venezuela to China in 2016. The constructed clone contained a modified version of the group II self-splicing intron P.li.LSUI2 near the junction between the E and NS1 genes, which were removed from the RNA transcripts by an easy-to-establish in vitro splicing reaction. Transfection of the spliced RNAs into BHK-21 cells led to the production of infectious progeny virus that resembled the parental virus. Finally, potential cis-acting RNA elements in ZIKV genomic RNA were identified based on this novel reverse genetics system, and the critical role of 5'-SLA promoter and 5'-3' cyclization sequences were characterized by a combination of different assays. Our results provide another stable and reliable reverse genetics system for ZIKV that will help study ZIKV infection and pathogenesis, and the novel self-splicing intron-based strategy could be further expanded for the construction of infectious clones from other emerging and reemerging flaviviruses.IMPORTANCE The ongoing Zika virus (ZIKV) outbreaks have drawn global concern due to the unexpected causal link to fetus microcephaly and other severe neurological complications. The infectious cDNA clones of ZIKV are critical for the research community to study the virus, understand the disease, and inform vaccine design and antiviral screening. A panel of existing technologies have been utilized to develop ZIKV infectious clones. Here, we successfully generated a stable

  1. Long-term survival and concomitant gene expression of ribozyme-transduced CD4+ T-lymphocytes in HIV-infected patients.

    Science.gov (United States)

    Macpherson, Janet L; Boyd, Maureen P; Arndt, Allison J; Todd, Alison V; Fanning, Gregory C; Ely, Julie A; Elliott, Fiona; Knop, Alison; Raponi, Mitch; Murray, John; Gerlach, Wayne; Sun, Lun-Quan; Penny, Ronald; Symonds, Geoff P; Carr, Andrew; Cooper, David A

    2005-05-01

    An anti-HIV-1 tat ribozyme, termed Rz2, has been shown to inhibit HIV-1 infection/replication and to decrease HIV-1-induced pathogenicity in T-lymphocyte cell lines and normal peripheral blood T-lymphocytes. We report here the results of a phase I gene transfer clinical trial using Rz2. Apheresis was used to obtain a peripheral blood cell population from each of four HIV-negative donors. After enrichment for CD4+ T-lymphocytes, ex vivo expansion and genetic manipulation (approximately equal aliquots of the cells were transduced with the ribozyme-containing (RRz2) and the control (LNL6) retroviral vector), these cells were infused into the corresponding HIV-1-positive twin recipient. Marking was assessed over an initial 24-week period and in total over an approximate 4-year period. The gene transfer procedure was shown to be safe, and technically feasible. Both RRz2- and LNL6-gene-containing peripheral blood mononuclear cells (PBMC) were detected at all time points examined to 4 years. There was concomitant gene construct expression in the absence of the need for ex vivo peripheral blood cell stimulation and there was no evidence of immune elimination of the neoR T-lymphocytes nor of silencing of the Moloney murine leukemia virus long terminal repeat. The proof of principle results reported here demonstrate safety and feasibility of this type of gene transfer approach. While not specifically tested, T-lymphocytes containing an anti-HIV gene construct may impact on HIV-1 viral load and CD4+ T-lymphocyte count, potentially representing a new therapeutic modality for HIV-1 infection. Copyright (c) 2005 John Wiley & Sons, Ltd.

  2. From Molecules to Life: Quantifying the Complexity of Chemical and Biological Systems in the Universe.

    Science.gov (United States)

    Böttcher, Thomas

    2017-12-19

    Life is a complex phenomenon and much research has been devoted to both understanding its origins from prebiotic chemistry and discovering life beyond Earth. Yet, it has remained elusive how to quantify this complexity and how to compare chemical and biological units on one common scale. Here, a mathematical description of molecular complexity was applied allowing to quantitatively assess complexity of chemical structures. This in combination with the orthogonal measure of information complexity resulted in a two-dimensional complexity space ranging over the entire spectrum from molecules to organisms. Entities with a certain level of information complexity directly require a functionally complex mechanism for their production or replication and are hence indicative for life-like systems. In order to describe entities combining molecular and information complexity, the term biogenic unit was introduced. Exemplified biogenic unit complexities were calculated for ribozymes, protein enzymes, multimeric protein complexes, and even an entire virus particle. Complexities of prokaryotic and eukaryotic cells, as well as multicellular organisms, were estimated. Thereby distinct evolutionary stages in complexity space were identified. The here developed approach to compare the complexity of biogenic units allows for the first time to address the gradual characteristics of prebiotic and life-like systems without the need for a definition of life. This operational concept may guide our search for life in the Universe, and it may direct the investigations of prebiotic trajectories that lead towards the evolution of complexity at the origins of life.

  3. Mercury and Selenium in Muscle and Target Organs of Scalloped Hammerhead Sharks Sphyrna lewini of the SE Gulf of California: Dietary Intake, Molar Ratios, Loads, and Human Health Risks.

    Science.gov (United States)

    Bergés-Tiznado, Magdalena E; Márquez-Farías, Fernando; Lara-Mendoza, Raúl E; Torres-Rojas, Yassir E; Galván-Magaña, Felipe; Bojórquez-Leyva, Humberto; Páez-Osuna, Federico

    2015-11-01

    Selenium and mercury were evaluated in muscle, liver, kidney, brain, and the stomach contents of juvenile scalloped hammerhead shark Sphyrna lewini. Se:Hg molar ratios were calculated. The average Hg levels in muscle ranged from 0.12 to 1.17 μg/g (wet weight); Hg was 1. Correlations were found for Hg in muscle with size, age, and weight, and also for Hg in liver with size, age, and weight. Hg in muscle was significantly positive correlated to Hg in brain as well as Hg in liver was correlated to Hg in kidney. The highest Hg in preys was for carangid fishes; scombrid and carangid fishes contributed with the highest Se levels. Results suggest that more than 98 % of the total Hg and 62 % of Se end up in muscle and might be affected by factors, such as geographical area, age, size, and feeding habits. The muscle of S. lewini should be consumed by people cautiously so as not to exceed the recommended intake per week.

  4. Probing adenine rings and backbone linkages using base specific isotope-edited Raman spectroscopy: application to group II intron ribozyme domain V.

    Science.gov (United States)

    Chen, Yuanyuan; Eldho, Nadukkudy V; Dayie, T Kwaku; Carey, Paul R

    2010-04-27

    with the differences in hydration radii. These subtle differences in electrostatic interactions may be related to observed variations in catalytic activity. For a reconstructed ribozyme comprising domains 1-3 (D123) connected in cis plus domain 5 (D5) supplied in trans, cleavage of spliced exon substrates in the presence of magnesium and K(+) or Cs(+) is more efficient than that in the presence of magnesium with Na(+) or Li(+).

  5. A computational approach for the annotation of hydrogen-bonded base interactions in crystallographic structures of the ribozymes

    Science.gov (United States)

    Hamdani, Hazrina Yusof; Artymiuk, Peter J.; Firdaus-Raih, Mohd

    2015-09-01

    A fundamental understanding of the atomic level interactions in ribonucleic acid (RNA) and how they contribute towards RNA architecture is an important knowledge platform to develop through the discovery of motifs from simple arrangements base pairs, to more complex arrangements such as triples and larger patterns involving non-standard interactions. The network of hydrogen bond interactions is important in connecting bases to form potential tertiary motifs. Therefore, there is an urgent need for the development of automated methods for annotating RNA 3D structures based on hydrogen bond interactions. COnnection tables Graphs for Nucleic ACids (COGNAC) is automated annotation system using graph theoretical approaches that has been developed for the identification of RNA 3D motifs. This program searches for patterns in the unbroken networks of hydrogen bonds for RNA structures and capable of annotating base pairs and higher-order base interactions, which ranges from triples to sextuples. COGNAC was able to discover 22 out of 32 quadruples occurrences of the Haloarcula marismortui large ribosomal subunit (PDB ID: 1FFK) and two out of three occurrences of quintuple interaction reported by the non-canonical interactions in RNA (NCIR) database. These and several other interactions of interest will be discussed in this paper. These examples demonstrate that the COGNAC program can serve as an automated annotation system that can be used to annotate conserved base-base interactions and could be added as additional information to established RNA secondary structure prediction methods.

  6. A computational approach for the annotation of hydrogen-bonded base interactions in crystallographic structures of the ribozymes

    Energy Technology Data Exchange (ETDEWEB)

    Hamdani, Hazrina Yusof, E-mail: hazrina@mfrlab.org [School of Biosciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 UKM Bangi (Malaysia); Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam, Kepala Batas (Malaysia); Artymiuk, Peter J., E-mail: p.artymiuk@sheffield.ac.uk [Dept. of Molecular Biology and Biotechnology, Firth Court, University of Sheffield, S10 T2N Sheffield (United Kingdom); Firdaus-Raih, Mohd, E-mail: firdaus@mfrlab.org [School of Biosciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 UKM Bangi (Malaysia)

    2015-09-25

    A fundamental understanding of the atomic level interactions in ribonucleic acid (RNA) and how they contribute towards RNA architecture is an important knowledge platform to develop through the discovery of motifs from simple arrangements base pairs, to more complex arrangements such as triples and larger patterns involving non-standard interactions. The network of hydrogen bond interactions is important in connecting bases to form potential tertiary motifs. Therefore, there is an urgent need for the development of automated methods for annotating RNA 3D structures based on hydrogen bond interactions. COnnection tables Graphs for Nucleic ACids (COGNAC) is automated annotation system using graph theoretical approaches that has been developed for the identification of RNA 3D motifs. This program searches for patterns in the unbroken networks of hydrogen bonds for RNA structures and capable of annotating base pairs and higher-order base interactions, which ranges from triples to sextuples. COGNAC was able to discover 22 out of 32 quadruples occurrences of the Haloarcula marismortui large ribosomal subunit (PDB ID: 1FFK) and two out of three occurrences of quintuple interaction reported by the non-canonical interactions in RNA (NCIR) database. These and several other interactions of interest will be discussed in this paper. These examples demonstrate that the COGNAC program can serve as an automated annotation system that can be used to annotate conserved base-base interactions and could be added as additional information to established RNA secondary structure prediction methods.

  7. Improving the efficiency of antisense and EGS methods.

    Science.gov (United States)

    Salavati, R; Altman, S

    1998-02-01

    Hammerhead ribozymes and stable stem loop structures function as inhibitors of 3'-5'-exonuclease degradation of external guide sequences (EGSs) when covalently linked to the 3'-end of EGS RNAs. This observation may be of use in improving the efficiency of gene inactivation techniques that use single-stranded RNA (e.g., antisense RNA, EGS RNA) in vivo.

  8. Age and growth of the Scalloped Hammerhead shark, Sphyrna lewini (Griffith and Smith, 1834, from the southern Brazilian coast Idade e crescimento do tubarão-martelo-entalhado, Sphyrna lewini (Griffith and Smith, 1834, da costa sul do Brasil

    Directory of Open Access Journals (Sweden)

    JE. Kotas

    2011-08-01

    Full Text Available Age and growth studies for the scalloped hammerhead shark, Sphyrna lewini (Griffith and Smith, 1834 caught along the southern Brazilian coast, were based on ring measurements of vertebrae sections of 115 males, 116 females and 14 unknown sexed sharks between 48 and 344 cm total length (TL. The von Bertalanffy growth models were best fit using back-calculated data. The growth parameters obtained for males, were L∞ = 266 cm; K = 0.05/year; L0 = 47 cm. For females, L∞ = 300 cm; K = 0.05/year; L0 = 51 cm. An adult female reached 217 cm TL and was 31.5 years old. On the other hand, an adult male was 29.5 years old and measured 234 cm TL. Longevity estimate for males and females was 55 years. Therefore, S. lewini is a long-lived fish. Ageing precision, based on the IAPE index, was 5.6%. Marginal Increment analysis based on MIR index from hammerheads smaller than 105 cm, compared with the percentual of opaque and hyaline bands found per month ageing whole vertebrae, showed an annual ring formation, i.e., in winter.O estudo da idade e do crescimento do tubarão-martelo-entalhado, Sphyrna lewini (Griffith and Smith, 1834, na costa sul do Brasil, baseou-se na leitura de anéis em seções de vértebras de 115 machos, 116 fêmeas e de 14 exemplares com sexo indeterminado, com comprimentos totais (CT entre 48 e 344 cm. Modelos de crescimento de von Bertalanffy foram mais bem ajustados aos dados de idade e comprimento retrocalculados, considerando sexos em separado. Os parâmetros de crescimento obtidos para os machos foram L∞ = 266 cm; K = 0,05/ano; L0 = 47 cm. Para as fêmeas L∞ = 300 cm; K = 0,05/ano; L0 = 51 cm. Uma fêmea adulta atingiu um CT de 217 cm e uma idade de 31,5 anos. Por sua vez, um macho adulto tinha 29,5 anos e CT de 234 cm. A estimativa de longevidade para machos e fêmeas foi de 55 anos. O índice de erro percentual médio (IAPE, que avalia a precisão na leitura de idades, foi de 5,6%. A análise do incremento marginal baseada no

  9. Probing Adenine Rings and Backbone Linkages Using Base Specific Isotope-Edited Raman Spectroscopy: Application to Group II Intron Ribozyme Domain V†

    Science.gov (United States)

    Chen, Yuanyuan; Eldho, Nadukkudy V.

    2010-01-01

    hydration radii. These subtle differences in electrostatic interactions may be related to observed variations in catalytic activity. For a reconstructed ribozyme comprising domains 1–3 (D123) connected in cis plus domain 5 (D5) supplied in trans, cleavage of spliced exon substrates in the presence of magnesium and K+ or Cs+ is more efficient than that in the presence of magnesium with Na+ or Li+. PMID:20225830

  10. Safety and Efficacy of Autologous CD34+ Hematopoietic Progenitor Cells Transduced with an Anti-Tat Ribozyme in a Multi-Center, Randomized, Placebo-Controlled, Phase II Gene Therapy Trial for the Human Immunodeficiency Virus

    Science.gov (United States)

    Mitsuyasu, Ronald T; Merigan, Thomas C; Carr, Andrew; Zack, Jerome A; Winters, Mark A; Workman, Cassy; Bloch, Mark; Lalezari, Jacob; Becker, Stephen; Thornton, Lorna; Akil, Bisher; Khanlou, Homayoon; Finlayson, Robert; McFarlane, Robert; Smith, Don E; Garsia, Roger; Ma, David; Law, Matthew; Murray, John M.; von Kalle, Christof; Ely, Julie A; Patino, Sharon M; Knop, Alison E; Wong, Philip; Todd, Alison V; Haughton, Margaret; Fuery, Caroline; Macpherson, Janet L; Symonds, Geoff P; Evans, Louise A; Pond, Susan M; Cooper, David A

    2009-01-01

    SUMMARY Gene transfer has potential as a once-only treatment that reduces viral load, preserves the immune system, and avoids lifetime highly active antiretroviral therapy. This study, the first randomized, double-blind, placebo-controlled, phase II cell-delivered gene transfer clinical trial, was conducted in 74 HIV-1 infected adults who received a tat/vpr specific anti-HIV ribozyme (OZ1) or placebo delivered in autologous CD34+ hematopoietic progenitor cells. There were no OZ1-related adverse events. There was no statistical difference in viral load between the OZ1 and placebo group at the primary end-point (average at weeks 47 and 48) but time weighted areas under the curve from weeks 40-48 and 40-100 were significantly lower in the OZ1 group. Throughout the 100 weeks, CD4+ lymphocyte counts were higher in the OZ1 group. This study provides the first indication that cell-delivered gene transfer is safe and biologically active in HIV patients and can be developed as a conventional therapeutic product. PMID:19219022

  11. RNA folding and catalysis mediated by iron (II.

    Directory of Open Access Journals (Sweden)

    Shreyas S Athavale

    Full Text Available Mg²⁺ shares a distinctive relationship with RNA, playing important and specific roles in the folding and function of essentially all large RNAs. Here we use theory and experiment to evaluate Fe²⁺ in the absence of free oxygen as a replacement for Mg²⁺ in RNA folding and catalysis. We describe both quantum mechanical calculations and experiments that suggest that the roles of Mg²⁺ in RNA folding and function can indeed be served by Fe²⁺. The results of quantum mechanical calculations show that the geometry of coordination of Fe²⁺ by RNA phosphates is similar to that of Mg²⁺. Chemical footprinting experiments suggest that the conformation of the Tetrahymena thermophila Group I intron P4-P6 domain RNA is conserved between complexes with Fe²⁺ or Mg²⁺. The catalytic activities of both the L1 ribozyme ligase, obtained previously by in vitro selection in the presence of Mg²⁺, and the hammerhead ribozyme are enhanced in the presence of Fe²⁺ compared to Mg²⁺. All chemical footprinting and ribozyme assays in the presence of Fe²⁺ were performed under anaerobic conditions. The primary motivation of this work is to understand RNA in plausible early earth conditions. Life originated during the early Archean Eon, characterized by a non-oxidative atmosphere and abundant soluble Fe²⁺. The combined biochemical and paleogeological data are consistent with a role for Fe²⁺ in an RNA World. RNA and Fe²⁺ could, in principle, support an array of RNA structures and catalytic functions more diverse than RNA with Mg²⁺ alone.

  12. Complexity explained

    CERN Document Server

    Erdi, Peter

    2008-01-01

    This book explains why complex systems research is important in understanding the structure, function and dynamics of complex natural and social phenomena. Readers will learn the basic concepts and methods of complex system research.

  13. Complex Narratives

    NARCIS (Netherlands)

    Simons, J.; Buckland, W.

    2014-01-01

    In the opening chapter, "Complex Narratives," Jan Simons brings together narratology, game theory, and complexity theory to untangle the intricate nature of complex narratives in contemporary cinema. He presents an overview of the different concepts - forking path narratives, mind-game films,

  14. (II) complexes

    African Journals Online (AJOL)

    activities of Schiff base tin (II) complexes. Neelofar1 ... Conclusion: All synthesized Schiff bases and their Tin (II) complexes showed high antimicrobial and ...... Singh HL. Synthesis and characterization of tin (II) complexes of fluorinated Schiff bases derived from amino acids. Spectrochim Acta Part A: Molec Biomolec.

  15. Complexity Plots

    KAUST Repository

    Thiyagalingam, Jeyarajan

    2013-06-01

    In this paper, we present a novel visualization technique for assisting the observation and analysis of algorithmic complexity. In comparison with conventional line graphs, this new technique is not sensitive to the units of measurement, allowing multivariate data series of different physical qualities (e.g., time, space and energy) to be juxtaposed together conveniently and consistently. It supports multivariate visualization as well as uncertainty visualization. It enables users to focus on algorithm categorization by complexity classes, while reducing visual impact caused by constants and algorithmic components that are insignificant to complexity analysis. It provides an effective means for observing the algorithmic complexity of programs with a mixture of algorithms and black-box software through visualization. Through two case studies, we demonstrate the effectiveness of complexity plots in complexity analysis in research, education and application. © 2013 The Author(s) Computer Graphics Forum © 2013 The Eurographics Association and Blackwell Publishing Ltd.

  16. carbene complexes

    Indian Academy of Sciences (India)

    Unknown

    Abstract. Reaction of oligomeric Cu(I) complexes [Cu{µ-S-C(=NR)(O–Ar–CH3)}]n with Lewis acids gave Cu(I) carbene complexes, which were characterized by 1H and 13C NMR spectroscopy. Cu(I) car- bene complexes could be directly generated from RNCS, Cu(I)–OAr and Lewis acids; this method can be used to ...

  17. Inducible Transgenic Models of BRCA1 Function

    Science.gov (United States)

    2000-10-01

    replaced by C, and H=C, U or A. Hammerhead ribozymes have been shown to effectively and selectively inhibit gene expression in bacteria, plants , cell...fulfills these criteria. In addition, this system permits early effects of trangene expression to be analyzed in normal epithelium. By permitting both the...shown). These findings suggest that rtTA trangene expression in MTB mice may demonstrate a greater degree of mammary specificity than is typically seen in

  18. Computational Complexity

    Directory of Open Access Journals (Sweden)

    J. A. Tenreiro Machado

    2017-02-01

    Full Text Available Complex systems (CS involve many elements that interact at different scales in time and space. The challenges in modeling CS led to the development of novel computational tools with applications in a wide range of scientific areas. The computational problems posed by CS exhibit intrinsic difficulties that are a major concern in Computational Complexity Theory. [...

  19. Complex narratives

    NARCIS (Netherlands)

    Simons, J.

    2008-01-01

    This paper brings together narratology, game theory, and complexity theory to untangle the intricate nature of complex narratives in contemporary cinema. It interrogates the different terms - forking-path narratives, mind-game films, modular narratives, multiple-draft films, database narratives,

  20. Communication Complexity

    Indian Academy of Sciences (India)

    Jaikumar Radhakrishnan

    Communication complexity. Strategy I. Alice x ∈ {0, 1}n. ⇒. ⇐. Bob y ∈ {0, 1}n. Naive strategy. Alice sends x to Bob. Bob tells Alice if x = y. Cost. Requires n + 1 bits of communication. Jaikumar Radhakrishnan. Communication Complexity ...

  1. Complexity Theory

    Science.gov (United States)

    Lee, William H K.

    2016-01-01

    A complex system consists of many interacting parts, generates new collective behavior through self organization, and adaptively evolves through time. Many theories have been developed to study complex systems, including chaos, fractals, cellular automata, self organization, stochastic processes, turbulence, and genetic algorithms.

  2. Complex derivatives

    Science.gov (United States)

    Battiston, Stefano; Caldarelli, Guido; Georg, Co-Pierre; May, Robert; Stiglitz, Joseph

    2013-03-01

    The intrinsic complexity of the financial derivatives market has emerged as both an incentive to engage in it, and a key source of its inherent instability. Regulators now faced with the challenge of taming this beast may find inspiration in the budding science of complex systems.

  3. Complex variables

    CERN Document Server

    Fisher, Stephen D

    1999-01-01

    The most important topics in the theory and application of complex variables receive a thorough, coherent treatment in this introductory text. Intended for undergraduates or graduate students in science, mathematics, and engineering, this volume features hundreds of solved examples, exercises, and applications designed to foster a complete understanding of complex variables as well as an appreciation of their mathematical beauty and elegance. Prerequisites are minimal; a three-semester course in calculus will suffice to prepare students for discussions of these topics: the complex plane, basic

  4. Carney Complex

    Science.gov (United States)

    ... at least one of the features listed. Major diagnostic features for Carney Complex Spotty skin pigmentation with ... called large cell calcifying Sertoli cell tumor (LCCST) Thyroid cancer Psammomatous melanotic schwannoma, meaning tumors that grow on ...

  5. Complex Covariance

    Directory of Open Access Journals (Sweden)

    Frieder Kleefeld

    2013-01-01

    Full Text Available According to some generalized correspondence principle the classical limit of a non-Hermitian quantum theory describing quantum degrees of freedom is expected to be the well known classical mechanics of classical degrees of freedom in the complex phase space, i.e., some phase space spanned by complex-valued space and momentum coordinates. As special relativity was developed by Einstein merely for real-valued space-time and four-momentum, we will try to understand how special relativity and covariance can be extended to complex-valued space-time and four-momentum. Our considerations will lead us not only to some unconventional derivation of Lorentz transformations for complex-valued velocities, but also to the non-Hermitian Klein-Gordon and Dirac equations, which are to lay the foundations of a non-Hermitian quantum theory.

  6. Dynamic nuclear polarization of nucleic acid with endogenously bound manganese

    Energy Technology Data Exchange (ETDEWEB)

    Wenk, Patricia [University of Tübingen, Werner Siemens Imaging Center and Department of Preclinical Imaging and Radiopharmacy (Germany); Kaushik, Monu; Richter, Diane [Goethe University, Institute of Physical und Theoretical Chemistry, Institute of Biophysical Chemistry und Center for Biomolecular Magnetic Resonance (BMRZ) (Germany); Vogel, Marc; Suess, Beatrix [Technical University Darmstadt, Department of Biology (Germany); Corzilius, Björn, E-mail: corzilius@em.uni-frankfurt.de [Goethe University, Institute of Physical und Theoretical Chemistry, Institute of Biophysical Chemistry und Center for Biomolecular Magnetic Resonance (BMRZ) (Germany)

    2015-09-15

    We report the direct dynamic nuclear polarization (DNP) of {sup 13}C nuclei of a uniformly [{sup 13}C,{sup 15}N]-labeled, paramagnetic full-length hammerhead ribozyme (HHRz) complex with Mn{sup 2+} where the enhanced polarization is fully provided by the endogenously bound metal ion and no exogenous polarizing agent is added. A {sup 13}C enhancement factor of ε = 8 was observed by intra-complex DNP at 9.4 T. In contrast, “conventional” indirect and direct DNP experiments were performed using AMUPol as polarizing agent where we obtained a {sup 1}H enhancement factor of ε ≈ 250. Comparison with the diamagnetic (Mg{sup 2+}) HHRz complex shows that the presence of Mn{sup 2+} only marginally influences the (DNP-enhanced) NMR properties of the RNA. Furthermore two-dimensional correlation spectra ({sup 15}N–{sup 13}C and {sup 13}C–{sup 13}C) reveal structural inhomogeneity in the frozen, amorphous state indicating the coexistence of several conformational states. These demonstrations of intra-complex DNP using an endogenous metal ion as well as DNP-enhanced MAS NMR of RNA in general yield important information for the development of new methods in structural biology.

  7. Complex chimerism

    Science.gov (United States)

    Ma, Kimberly K.; Petroff, Margaret G.; Coscia, Lisa A.; Armenti, Vincent T.; Adams Waldorf, Kristina M.

    2013-01-01

    Thousands of women with organ transplantation have undergone successful pregnancies, however little is known about how the profound immunologic changes associated with pregnancy might influence tolerance or rejection of the allograft. Pregnant women with a solid organ transplant are complex chimeras with multiple foreign cell populations from the donor organ, fetus, and mother of the pregnant woman. We consider the impact of complex chimerism and pregnancy-associated immunologic changes on tolerance of the allograft both during pregnancy and the postpartum period. Mechanisms of allograft tolerance are likely dynamic during pregnancy and affected by the influx of fetal microchimeric cells, HLA relationships (between the fetus, pregnant woman and/or donor), peripheral T cell tolerance to fetal cells, and fetal minor histocompatibility antigens. Further research is necessary to understand the complex immunology during pregnancy and the postpartum period of women with a solid organ transplant. PMID:23974274

  8. Complex analysis

    CERN Document Server

    Freitag, Eberhard

    2005-01-01

    The guiding principle of this presentation of ``Classical Complex Analysis'' is to proceed as quickly as possible to the central results while using a small number of notions and concepts from other fields. Thus the prerequisites for understanding this book are minimal; only elementary facts of calculus and algebra are required. The first four chapters cover the essential core of complex analysis: - differentiation in C (including elementary facts about conformal mappings) - integration in C (including complex line integrals, Cauchy's Integral Theorem, and the Integral Formulas) - sequences and series of analytic functions, (isolated) singularities, Laurent series, calculus of residues - construction of analytic functions: the gamma function, Weierstrass' Factorization Theorem, Mittag-Leffler Partial Fraction Decomposition, and -as a particular highlight- the Riemann Mapping Theorem, which characterizes the simply connected domains in C. Further topics included are: - the theory of elliptic functions based on...

  9. Complex Analysis

    CERN Document Server

    Stein, Elias M

    2009-01-01

    With this second volume, we enter the intriguing world of complex analysis. From the first theorems on, the elegance and sweep of the results is evident. The starting point is the simple idea of extending a function initially given for real values of the argument to one that is defined when the argument is complex. From there, one proceeds to the main properties of holomorphic functions, whose proofs are generally short and quite illuminating: the Cauchy theorems, residues, analytic continuation, the argument principle.With this background, the reader is ready to learn a wealth of additional m

  10. Complex manifolds

    CERN Document Server

    Morrow, James

    2006-01-01

    This book, a revision and organization of lectures given by Kodaira at Stanford University in 1965-66, is an excellent, well-written introduction to the study of abstract complex (analytic) manifolds-a subject that began in the late 1940's and early 1950's. It is largely self-contained, except for some standard results about elliptic partial differential equations, for which complete references are given. -D. C. Spencer, MathSciNet The book under review is the faithful reprint of the original edition of one of the most influential textbooks in modern complex analysis and geometry. The classic

  11. Managing Complexity

    DEFF Research Database (Denmark)

    Maylath, Bruce; Vandepitte, Sonia; Minacori, Patricia

    2013-01-01

    This article discusses the largest and most complex international learning-by-doing project to date- a project involving translation from Danish and Dutch into English and editing into American English alongside a project involving writing, usability testing, and translation from English into Dutch...

  12. phenanthroline complexes

    Indian Academy of Sciences (India)

    structural analyses. Mass spectral studies of the complexes indicate both the compounds to produce identical cationic species viz., [Co(phen)2Cl2]+ in methanol solution. ... Cobalt(III); X-ray structure; Catecholase activity; DNA cleavage; Anti-cancer activity. 1. ..... necrotic as judged by the staining, nuclear morphology.

  13. Lecithin Complex

    African Journals Online (AJOL)

    China). Lecithin from soya bean was a product of. Sangon (Shanghai, China). Methanol of HPLC grade was purchased from Tedia (USA). Other chemicals used were of analytical grade. Preparation of polydatin-lecithin complex. Polydatin (200 mg) and lecithin (400 mg) were dissolved in 50 mL of tetrahydrofuran and stirred.

  14. Complex Criminality

    NARCIS (Netherlands)

    Bruin, D.; Abels, D.; van der Wilt, H.

    2016-01-01

    This book presents a collection of essays on the wide diversity of meanings of complex criminality. These essays were written to commemorate a national gathering of PhD candidates, from criminal law departments of different universities, at the University of Amsterdam on the 6th of June 2014.

  15. Complex Networks

    CERN Document Server

    Evsukoff, Alexandre; González, Marta

    2013-01-01

    In the last decade we have seen the emergence of a new inter-disciplinary field focusing on the understanding of networks which are dynamic, large, open, and have a structure sometimes called random-biased. The field of Complex Networks is helping us better understand many complex phenomena such as the spread of  deseases, protein interactions, social relationships, to name but a few. Studies in Complex Networks are gaining attention due to some major scientific breakthroughs proposed by network scientists helping us understand and model interactions contained in large datasets. In fact, if we could point to one event leading to the widespread use of complex network analysis is the availability of online databases. Theories of Random Graphs from Erdös and Rényi from the late 1950s led us to believe that most networks had random characteristics. The work on large online datasets told us otherwise. Starting with the work of Barabási and Albert as well as Watts and Strogatz in the late 1990s, we now know th...

  16. peroxo complexes

    Indian Academy of Sciences (India)

    Administrator

    The investigation of dioxygen binding and activation in dinuclear iron complexes has attracted recent interest because of the presence of carboxylate bridged dinuclear iron sites in several biologically important proteins, such as the R2 protein of ribonucleotide reductase, the hydroxylase component of methane ...

  17. carbohydrate complexes

    Indian Academy of Sciences (India)

    ferrocene-carbohydrate conjugates38,39 have lead to the design and study of the cytotoxic activity of metal com- plexes containing carbohydrate ligands. Hence, here we present the detailed synthesis and characteriza- tion of the carbohydrate triazole ligands and their Pd- complexes together with the crystal structures of ...

  18. Ntem Complex

    African Journals Online (AJOL)

    Zena

    New ages were obtained from charnockites and tonalites collected in the So'o Group in the Ntem Complex. The rocks were analyzed for their petrography, tectonics and 207Pb/206Pb zircon minimum ages of their zircons as well as .... Owona, Department of Earth Sciences, Faculty of Science, University of Douala, P.O. Box.

  19. Complex chemistry with complex compounds

    Directory of Open Access Journals (Sweden)

    Eichler Robert

    2016-01-01

    Full Text Available In recent years gas-phase chemical studies assisted by physical pre-separation allowed for the investigation of fragile single molecular species by gas-phase chromatography. The latest success with the heaviest group 6 transactinide seaborgium is highlighted. The formation of a very volatile hexacarbonyl compound Sg(CO6 was observed similarly to its lighter homologues molybdenum and tungsten. The interactions of these gaseous carbonyl complex compounds with quartz surfaces were investigated by thermochromatography. Second-generation experiments are under way to investigate the intramolecular bond between the central metal atom of the complexes and the ligands addressing the influence of relativistic effects in the heaviest compounds. Our contribution comprises some aspects of the ongoing challenging experiments as well as an outlook towards other interesting compounds related to volatile complex compounds in the gas phase.

  20. Managing Complexity

    Energy Technology Data Exchange (ETDEWEB)

    Chassin, David P.; Posse, Christian; Malard, Joel M.

    2004-08-01

    Physical analogs have shown considerable promise for understanding the behavior of complex adaptive systems, including macroeconomics, biological systems, social networks, and electric power markets. Many of today’s most challenging technical and policy questions can be reduced to a distributed economic control problem. Indeed, economically-based control of large-scale systems is founded on the conjecture that the price-based regulation (e.g., auctions, markets) results in an optimal allocation of resources and emergent optimal system control. This paper explores the state of the art in the use physical analogs for understanding the behavior of some econophysical systems and to deriving stable and robust control strategies for them. In particular we review and discussion applications of some analytic methods based on the thermodynamic metaphor according to which the interplay between system entropy and conservation laws gives rise to intuitive and governing global properties of complex systems that cannot be otherwise understood.

  1. Complex Questions Promote Complex Thinking

    Science.gov (United States)

    Degener, Sophie; Berne, Jennifer

    2017-01-01

    Intermediate-grade teachers often express concerns about meeting the Common Core State Standards for Reading, primarily because of the emphasis on deep understanding of complex texts. No matter how difficult the text, if teachers demand little of the reading, student meaning making is not challenged. This article offers a tool for teachers to…

  2. Prebiotic chemistry: Ribozyme takes its vitamins

    Science.gov (United States)

    Burrows, Cynthia J.

    2013-11-01

    Selection of an RNA catalyst that can use the vitamin thiamin to catalyse a key metabolic decarboxylation reaction has broad implications for understanding the role of RNA in the early stages of chemical evolution.

  3. Fatal Fusarium solani species complex infections in elasmobranchs: the first case report for black spotted stingray (Taeniura melanopsila) and a literature review.

    Science.gov (United States)

    Fernando, Nimal; Hui, Suk-Wai; Tsang, Chi-Ching; Leung, Shui-Yee; Ngan, Antonio H Y; Leung, Raymond W W; Groff, Joseph M; Lau, Susanna K P; Woo, Patrick C Y

    2015-07-01

    Fusarium species are environmental saprophytic fungi. Among the many Fusarium species, members of the Fusarium solani species complex (FSSC) are the most prevalent and virulent in causing human and animal infections. In this study, we describe the first case of fatal FSSC infection in a black spotted stingray and three concomitant infections in scalloped hammerhead sharks. In the stingray, cutaneous lesions were characterised by ulcers and haemorrhage of the ventral pectoral fin, or 'ray', especially around the head; while cutaneous lesions in the sharks were characterised by ulcers, haemorrhage, as well as white and purulent exudates at the cephalic canals of the cephalofoil and lateral line. Histological sections of the cutaneous lesions revealed slender (1-4 μm in diameter), branching, septate fungal hyphae. Internal transcribed spacer region and 28S nrDNA sequencing of the fungal isolates from the fish showed two isolates were F. keratoplasticum (FSSC 2) and the other two were FSSC 12. Environmental investigation revealed the FSSC strains isolated from water and biofilms in tanks that housed the elasmobranchs were also F. keratoplasticum and FSSC 12. Fusarium is associated with major infections in elasmobranchs and FSSC 12 is an emerging cause of infections in marine animals. DNA sequencing is so far the most reliable method for accurate identification of Fusarium species. © 2015 Blackwell Verlag GmbH.

  4. Complex variables

    CERN Document Server

    Flanigan, Francis J

    2010-01-01

    A caution to mathematics professors: Complex Variables does not follow conventional outlines of course material. One reviewer noting its originality wrote: ""A standard text is often preferred [to a superior text like this] because the professor knows the order of topics and the problems, and doesn't really have to pay attention to the text. He can go to class without preparation."" Not so here-Dr. Flanigan treats this most important field of contemporary mathematics in a most unusual way. While all the material for an advanced undergraduate or first-year graduate course is covered, discussion

  5. Complex variables

    CERN Document Server

    Taylor, Joseph L

    2011-01-01

    The text covers a broad spectrum between basic and advanced complex variables on the one hand and between theoretical and applied or computational material on the other hand. With careful selection of the emphasis put on the various sections, examples, and exercises, the book can be used in a one- or two-semester course for undergraduate mathematics majors, a one-semester course for engineering or physics majors, or a one-semester course for first-year mathematics graduate students. It has been tested in all three settings at the University of Utah. The exposition is clear, concise, and lively

  6. Mechanistic Insights Into Catalytic RNA-Protein Complexes Involved in Translation of the Genetic Code.

    Science.gov (United States)

    Routh, Satya B; Sankaranarayanan, Rajan

    2017-01-01

    The contemporary world is an "RNA-protein world" rather than a "protein world" and tracing its evolutionary origins is of great interest and importance. The different RNAs that function in close collaboration with proteins are involved in several key physiological processes, including catalysis. Ribosome-the complex megadalton cellular machinery that translates genetic information encoded in nucleotide sequence to amino acid sequence-epitomizes such an association between RNA and protein. RNAs that can catalyze biochemical reactions are known as ribozymes. They usually employ general acid-base catalytic mechanism, often involving the 2'-OH of RNA that activates and/or stabilizes a nucleophile during the reaction pathway. The protein component of such RNA-protein complexes (RNPCs) mostly serves as a scaffold which provides an environment conducive for the RNA to function, or as a mediator for other interacting partners. In this review, we describe those RNPCs that are involved at different stages of protein biosynthesis and in which RNA performs the catalytic function; the focus of the account is on highlighting mechanistic aspects of these complexes. We also provide a perspective on such associations in the context of proofreading during translation of the genetic code. The latter aspect is not much appreciated and recent works suggest that this is an avenue worth exploring, since an understanding of the subject can provide useful insights into how RNAs collaborate with proteins to ensure fidelity during these essential cellular processes. It may also aid in comprehending evolutionary aspects of such associations. © 2017 Elsevier Inc. All rights reserved.

  7. Complex dynamics

    CERN Document Server

    Carleson, Lennart

    1993-01-01

    Complex dynamics is today very much a focus of interest. Though several fine expository articles were available, by P. Blanchard and by M. Yu. Lyubich in particular, until recently there was no single source where students could find the material with proofs. For anyone in our position, gathering and organizing the material required a great deal of work going through preprints and papers and in some cases even finding a proof. We hope that the results of our efforts will be of help to others who plan to learn about complex dynamics and perhaps even lecture. Meanwhile books in the field a. re beginning to appear. The Stony Brook course notes of J. Milnor were particularly welcome and useful. Still we hope that our special emphasis on the analytic side will satisfy a need. This book is a revised and expanded version of notes based on lectures of the first author at UCLA over several \\Vinter Quarters, particularly 1986 and 1990. We owe Chris Bishop a great deal of gratitude for supervising the production of cour...

  8. and complex

    Directory of Open Access Journals (Sweden)

    Kamrin Ken

    2017-01-01

    Full Text Available Granular materials have a strange propensity to behave as either a complex media or a simple media depending on the precise question being asked. This review paper offers a summary of granular flow rheologies for well-developed or steady-state motion, and seeks to explain this dichotomy through the vast range of complexity intrinsic to these models. A key observation is that to achieve accuracy in predicting flow fields in general geometries, one requires a model that accounts for a number of subtleties, most notably a nonlocal effect to account for cooperativity in the flow as induced by the finite size of grains. On the other hand, forces and tractions that develop on macro-scale, submerged boundaries appear to be minimally affected by grain size and, barring very rapid motions, are well represented by simple rate-independent frictional plasticity models. A major simplification observed in experiments of granular intrusion, which we refer to as the ‘resistive force hypothesis’ of granular Resistive Force Theory, can be shown to arise directly from rate-independent plasticity. Because such plasticity models have so few parameters, and the major rheological parameter is a dimensionless internal friction coefficient, some of these simplifications can be seen as consequences of scaling.

  9. Cosmic Complexity

    Science.gov (United States)

    Mather, John C.

    2012-01-01

    What explains the extraordinary complexity of the observed universe, on all scales from quarks to the accelerating universe? My favorite explanation (which I certainty did not invent) ls that the fundamental laws of physics produce natural instability, energy flows, and chaos. Some call the result the Life Force, some note that the Earth is a living system itself (Gaia, a "tough bitch" according to Margulis), and some conclude that the observed complexity requires a supernatural explanation (of which we have many). But my dad was a statistician (of dairy cows) and he told me about cells and genes and evolution and chance when I was very small. So a scientist must look for me explanation of how nature's laws and statistics brought us into conscious existence. And how is that seemll"!gly Improbable events are actually happening a!1 the time? Well, the physicists have countless examples of natural instability, in which energy is released to power change from simplicity to complexity. One of the most common to see is that cooling water vapor below the freezing point produces snowflakes, no two alike, and all complex and beautiful. We see it often so we are not amazed. But physlc!sts have observed so many kinds of these changes from one structure to another (we call them phase transitions) that the Nobel Prize in 1992 could be awarded for understanding the mathematics of their common features. Now for a few examples of how the laws of nature produce the instabilities that lead to our own existence. First, the Big Bang (what an insufficient name!) apparently came from an instability, in which the "false vacuum" eventually decayed into the ordinary vacuum we have today, plus the most fundamental particles we know, the quarks and leptons. So the universe as a whole started with an instability. Then, a great expansion and cooling happened, and the loose quarks, finding themselves unstable too, bound themselves together into today's less elementary particles like protons and

  10. Structural Analyses of Avocado sunblotch viroid Reveal Differences in the Folding of Plus and Minus RNA Strands

    Directory of Open Access Journals (Sweden)

    Clémentine Delan-Forino

    2014-01-01

    Full Text Available Viroids are small pathogenic circular single-stranded RNAs, present in two complementary sequences, named plus and minus, in infected plant cells. A high degree of complementarities between different regions of the RNAs allows them to adopt complex structures. Since viroids are naked non-coding RNAs, interactions with host factors appear to be closely related to their structural and catalytic characteristics. Avocado sunblotch viroid (ASBVd, a member of the family Avsunviroidae, replicates via a symmetric RNA-dependant rolling-circle process, involving self-cleavage via hammerhead ribozymes. Consequently, it is assumed that ASBVd plus and minus strands adopt similar structures. Moreover, by computer analyses, a quasi-rod-like secondary structure has been predicted. Nevertheless, secondary and tertiary structures of both polarities of ASBVd remain unsolved. In this study, we analyzed the characteristic of each strand of ASBVd through biophysical analyses. We report that ASBVd transcripts of plus and minus polarities exhibit differences in electrophoretic mobility under native conditions and in thermal denaturation profiles. Subsequently, the secondary structures of plus and minus polarities of ASBVd were probed using the RNA-selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE method. The models obtained show that both polarities fold into different structures. Moreover, our results suggest the existence of a kissing-loop interaction within the minus strand that may play a role in in vivo viroid life cycle.

  11. Development of an RNA-based theophylline-specific microarray biosensor

    Science.gov (United States)

    Jordan, Katherine M.

    We are developing an extremely sensitive and compact biosensor that is adaptable to a variety of target analytes. Hammerhead ribozymes have been engineered such that they rearrange from a catalytically inactive to an active conformation upon binding to a target molecule. A donor-acceptor fluorophore pair is coupled to the substrate RNA of such an aptamer, to form a complex referred to as an aptazyme, to monitor real-time cleavage activity in a fluid environment. The fluorophores interact by fluorescence resonance energy transfer (FRET) until binding of the target molecule, when the FRET signal breaks down as the substrate is cleaved and the products dissociate. FRET assays with immobilized aptazymes and using total internal reflection fluorescence (TIRF) microscopy on the single-molecule scale are presented showing an enhancement of substrate cleavage in the presence of theophylline over background. The aptazyme is hybridized onto a DNA microarray and incorporated into a chip specifically designed to allow for measurement in a controlled fluid environment. The use of these microarrays allows for either one spot, or a series of spots, to be addressed independently within the biosensor. This allows for multiple analytes to be tested simultaneously. An enhancement in the substrate cleavage is again observed in the presence of theophylline. Results are presented toward the characterization of a theophylline-specific aptamer-based biosensor using this RNA microarray platform and analogous measurement techniques.

  12. Complex analysis and geometry

    CERN Document Server

    Silva, Alessandro

    1993-01-01

    The papers in this wide-ranging collection report on the results of investigations from a number of linked disciplines, including complex algebraic geometry, complex analytic geometry of manifolds and spaces, and complex differential geometry.

  13. Durophagy in sharks: feeding mechanics of the hammerhead Sphyrna tiburo.

    Science.gov (United States)

    Wilga, C D; Motta, P J

    2000-09-01

    This study investigates the motor pattern and head movements during feeding of a durophagus shark, the bonnethead Sphyrna tiburo, using electromyography and simultaneous high-speed video. Sphyrna tiburo feeds almost exclusively on hard-shelled crabs, with shrimp and fish taken occasionally. It captures crabs by ram feeding, then processes or reduces the prey by crushing it between molariform teeth, finally transporting the prey by suction for swallowing. The prey-crushing mechanism is distinct from that of ram or bite capture and suction transport. This crushing mechanism is accomplished by altering the duration of jaw adductor muscle activity and modifying jaw kinematics by the addition of a second jaw-closing phase. In crushing events, motor activity of the jaw adductor muscles continues (biting of the prey occurs as the jaws close and continues after the jaws have closed) throughout a second jaw-closing phase, unlike capture and transport events during which motor activity (biting) ceases at jaw closure. Sphyrna tiburo is able to take advantage of a resource (hard prey) that is not readily available to most sharks by utilizing a suite of durophagous characteristics: molariform teeth, a modified jaw protrusor muscle, altered jaw adductor activity and modified jaw kinematics. Sphyrna tiburo is a specialist feeder on crab prey as demonstrated by the lack of differences in kinematic or motor patterns when offered prey of differing hardness and its apparent lack of ability to modulate its behavior when feeding on other prey. Functional patterns are altered and coupled with modifications in dental and jaw morphology to produce diverse crushing behaviors in elasmobranchs.

  14. Response of juvenile scalloped hammerhead sharks to electric stimuli.

    Science.gov (United States)

    Kajiura, Stephen M; Fitzgerald, Timothy P

    2009-01-01

    Sharks can use their electrosensory system to detect electric fields in their environment. Measurements of their electrosensitivity are often derived by calculating the voltage gradient from a model of the charge distribution for an ideal dipole. This study measures the charge distribution around a dipole in seawater and confirms the close correspondence with the model. From this, it is possible to predict how the sharks will respond to dipolar electric fields comprised of differing parameters. We tested these predictions by exposing sharks to different sized dipoles and levels of applied current that simulated the bioelectric fields of their natural prey items. The sharks initiated responses from a significantly greater distance with larger dipole sizes and also from a significantly greater distance with increasing levels of electric current. This study is the first to provide empirical evidence supporting a popular theoretical model and test predictions about how sharks will respond to a variety of different electric stimuli.

  15. Photocytotoxic lanthanide complexes

    Indian Academy of Sciences (India)

    and Tb(III) complexes in UV-A light of 350 nm.61 The complexes are thus of importance for therapeutic appli- cations in the treatment of accessible tumours like skin melanoma. 3.3 Photoactive non-macrocyclic lanthanide complexes. Lanthanide complexes of non-macrocyclic ligands have recently been studied mainly by ...

  16. Complex differential geometry

    CERN Document Server

    Zheng, Fangyang

    2002-01-01

    The theory of complex manifolds overlaps with several branches of mathematics, including differential geometry, algebraic geometry, several complex variables, global analysis, topology, algebraic number theory, and mathematical physics. Complex manifolds provide a rich class of geometric objects, for example the (common) zero locus of any generic set of complex polynomials is always a complex manifold. Yet complex manifolds behave differently than generic smooth manifolds; they are more coherent and fragile. The rich yet restrictive character of complex manifolds makes them a special and interesting object of study. This book is a self-contained graduate textbook that discusses the differential geometric aspects of complex manifolds. The first part contains standard materials from general topology, differentiable manifolds, and basic Riemannian geometry. The second part discusses complex manifolds and analytic varieties, sheaves and holomorphic vector bundles, and gives a brief account of the surface classifi...

  17. Complex and symplectic geometry

    CERN Document Server

    Medori, Costantino; Tomassini, Adriano

    2017-01-01

    This book arises from the INdAM Meeting "Complex and Symplectic Geometry", which was held in Cortona in June 2016. Several leading specialists, including young researchers, in the field of complex and symplectic geometry, present the state of the art of their research on topics such as the cohomology of complex manifolds; analytic techniques in Kähler and non-Kähler geometry; almost-complex and symplectic structures; special structures on complex manifolds; and deformations of complex objects. The work is intended for researchers in these areas.

  18. Adaptive leadership: fighting complexity with complexity

    OpenAIRE

    Smith, Peter

    2014-01-01

    CHDS State/Local Contemporary crises have become increasingly complex and the methods of leading through them have failed to keep pace. If it is assumed that leadership matters—that it has a legitimate effect on the outcome of a crisis, then leaders have a duty to respond to that adaptation with modifications of their own. Using literature sources, the research explores crisis complexity, crisis leadership, and alternative leadership strategies. Specifically, the research evaluates the app...

  19. Oligocyclopentadienyl transition metal complexes

    Energy Technology Data Exchange (ETDEWEB)

    de Azevedo, Cristina G.; Vollhardt, K. Peter C.

    2002-01-18

    Synthesis, characterization, and reactivity studies of oligocyclopentadienyl transition metal complexes, namely those of fulvalene, tercyclopentadienyl, quatercyclopentadienyl, and pentacyclopentadienyl(cyclopentadienyl) are the subject of this account. Thermal-, photo-, and redox chemistries of homo- and heteropolynuclear complexes are described.

  20. Complex carbohydrates (image)

    Science.gov (United States)

    ... foods such as peas, beans, whole grains, and vegetables. Both simple and complex carbohydrates are turned to ... majority of carbohydrates should come from complex carbohydrates (starches) and naturally occurring sugars, rather than processed or ...

  1. Complex systems biology

    OpenAIRE

    Ma'ayan, Avi

    2017-01-01

    Complex systems theory is concerned with identifying and characterizing common design elements that are observed across diverse natural, technological and social complex systems. Systems biology, a more holistic approach to study molecules and cells in biology, has advanced rapidly in the past two decades. However, not much appreciation has been granted to the realization that the human cell is an exemplary complex system. Here, I outline general design principles identified in many complex s...

  2. The simple complex numbers

    OpenAIRE

    Zalesny, Jaroslaw

    2008-01-01

    A new simple geometrical interpretation of complex numbers is presented. It differs from their usual interpretation as points in the complex plane. From the new point of view the complex numbers are rather operations on vectors than points. Moreover, in this approach the real, imaginary and complex numbers have similar interpretation. They are simply some operations on vectors. The presented interpretation is simpler, more natural, and better adjusted to possible applications in geometry and ...

  3. Group I aptazymes as genetic regulatory switches

    Directory of Open Access Journals (Sweden)

    Knudsen Scott M

    2002-12-01

    Full Text Available Abstract Background Allosteric ribozymes (aptazymes that have extraordinary activation parameters have been generated in vitro by design and selection. For example, hammerhead and ligase ribozymes that are activated by small organic effectors and protein effectors have been selected from random sequence pools appended to extant ribozymes. Many ribozymes, especially self-splicing introns, are known control gene regulation or viral replication in vivo. We attempted to generate Group I self-splicing introns that were activated by a small organic effector, theophylline, and to show that such Group I aptazymes could mediate theophylline-dependent splicing in vivo. Results By appending aptamers to the Group I self-splicing intron, we have generated a Group I aptazyme whose in vivo splicing is controlled by exogenously added small molecules. Substantial differences in gene regulation could be observed with compounds that differed by as little as a single methyl group. The effector-specificity of the Group I aptazyme could be rationally engineered for new effector molecules. Conclusion Group I aptazymes may find applications as genetic regulatory switches for generating conditional knockouts at the level of mRNA or for developing economically viable gene therapies.

  4. The Visibility Complex

    NARCIS (Netherlands)

    Pocchiola, Michel; Vegter, Gert

    1993-01-01

    We introduce the visibility complex of a collection O of n pairwise disjoint convex objects in the plane. This 2–dimensional cell complex may be considered as a generalization of the tangent visibility graph of O. Its space complexity k is proportional to the size of the tangent visibility graph. We

  5. Cobalt(III) complex

    Indian Academy of Sciences (India)

    Administrator

    . 2 radicals ... Crystal structure of the complex was determined by X-ray diffraction and is reported elsewhere. 5. The complex is stable towards hydrolysis at least for 10 h as checked by its ..... served in Co(III) aquo-ammonia complexes where.

  6. Complex variables I essentials

    CERN Document Server

    Solomon, Alan D

    2013-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Complex Variables I includes functions of a complex variable, elementary complex functions, integrals of complex functions in the complex plane, sequences and series, and poles and r

  7. How to understand atomistic molecular dynamics simulations of RNA and protein-RNA complexes?

    Czech Academy of Sciences Publication Activity Database

    Šponer, Jiří; Krepl, Miroslav; Banáš, P.; Kührová, P.; Zgarbová, M.; Jurečka, P.; Havrila, Marek; Otyepka, M.

    2017-01-01

    Roč. 8, č. 3 (2017), č. článku e1405. ISSN 1757-7004 R&D Projects: GA ČR(CZ) GBP305/12/G034 Grant - others:GA MŠk(CZ) LO1305 Institutional support: RVO:68081707 Keywords : hepatitis -delta-virus * amber force-field * free-energy landscape * hdv ribozyme Subject RIV: BO - Biophysics Impact factor: 4.838, year: 2016

  8. Simplicial complexes of graphs

    CERN Document Server

    Jonsson, Jakob

    2008-01-01

    A graph complex is a finite family of graphs closed under deletion of edges. Graph complexes show up naturally in many different areas of mathematics, including commutative algebra, geometry, and knot theory. Identifying each graph with its edge set, one may view a graph complex as a simplicial complex and hence interpret it as a geometric object. This volume examines topological properties of graph complexes, focusing on homotopy type and homology. Many of the proofs are based on Robin Forman's discrete version of Morse theory. As a byproduct, this volume also provides a loosely defined toolbox for attacking problems in topological combinatorics via discrete Morse theory. In terms of simplicity and power, arguably the most efficient tool is Forman's divide and conquer approach via decision trees; it is successfully applied to a large number of graph and digraph complexes.

  9. Complex Systems and Dependability

    CERN Document Server

    Zamojski, Wojciech; Sugier, Jaroslaw

    2012-01-01

    Typical contemporary complex system is a multifaceted amalgamation of technical, information, organization, software and human (users, administrators and management) resources. Complexity of such a system comes not only from its involved technical and organizational structure but mainly from complexity of information processes that must be implemented in the operational environment (data processing, monitoring, management, etc.). In such case traditional methods of reliability analysis focused mainly on technical level are usually insufficient in performance evaluation and more innovative meth

  10. More about inorganic complexes

    OpenAIRE

    Vella, Alfred;

    1980-01-01

    This article is a sequel to the one which appeared earlier in this Journal ("Inorganic Complexes: An Introduction" Hyphen VOil. I, Number 3, Spring 1978, pp. 31 - 39) and which dealt with certain aspects of the chemistry of complexes, notably: their definition, stereochemistry, nomenclature and some of their chemical properties. In this article we shall examine the stability of complexes and review some of the applications of coordination compound" in chemis~ry.

  11. Tuberculosis in complex emergencies.

    Science.gov (United States)

    Coninx, Rudi

    2007-08-01

    This paper describes the key factors and remaining challenges for tuberculosis (TB) control programmes in complex emergencies. A complex emergency is "a humanitarian crisis in a country, region or society where there is total or considerable breakdown of authority resulting from internal or external conflict and which requires an international response that goes beyond the mandate or capacity of any single agency and/or the ongoing United Nations country programme." Some 200 million people are believed to live in countries affected by complex emergencies; almost all of these are developing countries that also bear the main burden of TB. The effects of complex emergencies impact on TB control programmes, interfering with the goals of identifying and curing TB patients and possibly leading to the emergence of MDR-TB. There are many detailed descriptions of aid interventions during complex emergencies; yet TB control programmes are absent from most of these reports. If TB is neglected, it may quickly result in increased morbidity and mortality, as was demonstrated in Bosnia and Herzegovina and in Somalia. TB is a major disease in complex emergencies and requires an appropriate public health response. While there is no manual to cover complex emergencies, the interagency manual for TB control in refugee and displaced populations provides valuable guidance. These programmes contribute to the body of evidence needed to compile such a manual, and should ensure that the experiences of TB control in complex emergencies lead to the establishment of evidence-based programmes.

  12. Introductory complex analysis

    CERN Document Server

    Silverman, Richard A

    1984-01-01

    A shorter version of A. I. Markushevich's masterly three-volume Theory of Functions of a Complex Variable, this edition is appropriate for advanced undergraduate and graduate courses in complex analysis. Numerous worked-out examples and more than 300 problems, some with hints and answers, make it suitable for independent study. 1967 edition.

  13. The visibility complex

    NARCIS (Netherlands)

    Pocchiola, M; Vegter, G

    We introduce the visibility complex (rr 2-dimensional regular cell complex) of a collection of n pairwise disjoint convex obstacles in the plane. It can be considered as a subdivision of the set of free rays (i.e., rays whose origins lie in free space, the complement of the obstacles). Its cells

  14. The Acacia Senegal complex

    Directory of Open Access Journals (Sweden)

    J. H. Ross

    1975-11-01

    Full Text Available A brief account of the present slate of knowledge of the species in the  Acacia senegal complex is given. A short description of each species is provided together with a key to the identification of the species. Attention is drawn to the taxonomic difficulties encountered within the complex.

  15. Complexity and valued landscapes

    Science.gov (United States)

    Michael M. McCarthy

    1979-01-01

    The variable "complexity," or "diversity," has received a great deal of attention in recent research efforts concerned with visual resource management, including the identification of complexity as one of the primary evaluation measures. This paper describes research efforts that support the hypothesis that the landscapes we value are those with...

  16. Is dense codeswitching complex?

    NARCIS (Netherlands)

    Dorleijn, M.

    2016-01-01

    In this paper the question is raised to what extent dense code switching can be considered complex. Psycholinguistic experiments indicate that code switching involves cognitive costs, both in production and comprehension, a conclusion that could indicate that code switching is indeed complex. In

  17. Conducting metal dithiolate complexes

    DEFF Research Database (Denmark)

    Underhill, A. E.; Ahmad, M. M.; Turner, D. J.

    1985-01-01

    Further work on the chemical composition of the one-dimensional metallic metal dithiolene complex Li-Pt(mnt) is reported. The electrical conduction and thermopower properties of the nickel and palladium complexes are reported and compared with those of the platinum compound...

  18. Visual Complexity: A Review

    Science.gov (United States)

    Donderi, Don C.

    2006-01-01

    The idea of visual complexity, the history of its measurement, and its implications for behavior are reviewed, starting with structuralism and Gestalt psychology at the beginning of the 20th century and ending with visual complexity theory, perceptual learning theory, and neural circuit theory at the beginning of the 21st. Evidence is drawn from…

  19. Photocytotoxic lanthanide complexes

    Indian Academy of Sciences (India)

    The chemistry of photoactive lanthanide complexes showing biological applications is of recent origin. Photodynamic therapy (PDT) is a non-invasive treatment modality of cancer using a photosensitizer drug and light. This review primarily focuses on different aspects of the chemistry of lanthanide complexes showing ...

  20. Thermochemiluminescent Cyclodextrin Complexes

    NARCIS (Netherlands)

    Luider, Theo M.; Hummelen, Jan C.; Koek, Johannes N.; Wynberg, Hans

    1990-01-01

    Thermochemiluminescent complexes of an adamantylideneadamantane 1,2-dioxetane and a cyclodextrin are non-volatile at the temperatures used to excite the thermochemiluminescence. The complexes can be encapsulated in immunosensitized microcapsules, e.g., liposomes, to provide a labeled immunoreagent

  1. Poor-data and data-poor species stock assessment using a Bayesian hierarchical approach.

    Science.gov (United States)

    Jiao, Yan; Cortés, Enric; Andrews, Kate; Guo, Feng

    2011-10-01

    Appropriate inference for stocks or species with low-quality data (poor data) or limited data (data poor) is extremely important. Hierarchical Bayesian methods are especially applicable to small-area, small-sample-size estimation problems because they allow poor-data species to borrow strength from species with good-quality data. We used a hammerhead shark complex as an example to investigate the advantages of using hierarchical Bayesian models in assessing the status of poor-data and data-poor exploited species. The hammerhead shark complex (Sphyrna spp.) along the Atlantic and Gulf of Mexico coasts of the United States is composed of three species: the scalloped hammerhead (S. lewini), the great hammerhead (S. mokarran), and the smooth hammerhead (S. zygaena) sharks. The scalloped hammerhead comprises 70-80% of the catch and has catch and relative abundance data of good quality, whereas great and smooth hammerheads have relative abundance indices that are both limited and of low quality presumably because of low stock density and limited sampling. Four hierarchical Bayesian state-space surplus production models were developed to simulate variability in population growth rates, carrying capacity, and catchability of the species. The results from the hierarchical Bayesian models were considerably more robust than those of the nonhierarchical models. The hierarchical Bayesian approach represents an intermediate strategy between traditional models that assume different population parameters for each species and those that assume all species share identical parameters. Use of the hierarchical Bayesian approach is suggested for future hammerhead shark stock assessments and for modeling fish complexes with species-specific data, because the poor-data species can borrow strength from the species with good data, making the estimation more stable and robust.

  2. A complex legacy

    Science.gov (United States)

    Moore, Cristopher

    2011-11-01

    In his tragically short life, Alan Turing helped define what computing machines are capable of, and where they reach inherent limits. His legacy is still felt every day, in areas ranging from computational complexity theory to cryptography and quantum computing.

  3. Complexity of Economical Systems

    National Research Council Canada - National Science Library

    G. P. Pavlos; A. C. Iliopoulos; L.P. Karakatsanis; M. Xenakis; E. Pavlos

    2015-01-01

    .... In addition a summary of an extended algorithm of nonlinear time series analysis is provided which is applied not only in economical time series but also in other physical complex systems (e.g. [22, 24...

  4. Complex Networks IX

    CERN Document Server

    Coronges, Kate; Gonçalves, Bruno; Sinatra, Roberta; Vespignani, Alessandro; Proceedings of the 9th Conference on Complex Networks; CompleNet 2018

    2018-01-01

    This book aims to bring together researchers and practitioners working across domains and research disciplines to measure, model, and visualize complex networks. It collects the works presented at the 9th International Conference on Complex Networks (CompleNet) 2018 in Boston, MA in March, 2018. With roots in physical, information and social science, the study of complex networks provides a formal set of mathematical methods, computational tools and theories to describe prescribe and predict dynamics and behaviors of complex systems. Despite their diversity, whether the systems are made up of physical, technological, informational, or social networks, they share many common organizing principles and thus can be studied with similar approaches. This book provides a view of the state-of-the-art in this dynamic field and covers topics such as group decision-making, brain and cellular connectivity, network controllability and resiliency, online activism, recommendation systems, and cyber security.

  5. Physical Sciences Complex

    Data.gov (United States)

    Federal Laboratory Consortium — This 88,000 square foot complex is used to investigate basic physical science in support of missile technology development. It incorporates office space, dedicated...

  6. Complex Strategic Choices

    DEFF Research Database (Denmark)

    Leleur, Steen

    . Complex Strategic Choices provides clear principles and methods which can guide and support strategic decision making to face the many current challenges. By considering ways in which planning practices can be renewed and exploring the possibilities for acquiring awareness and tools to add value...... and students in the field of planning and decision analysis as well as practitioners dealing with strategic analysis and decision making. More broadly, Complex Strategic Choices acts as guide for professionals and students involved in complex planning tasks across several fields such as business...... to strategic decision making, Complex Strategic Choices presents a methodology which is further illustrated by a number of case studies and example applications. Dr. Techn. Steen Leleur has adapted previously established research based on feedback and input from various conferences, journals and students...

  7. Pigment-protein complexes

    Energy Technology Data Exchange (ETDEWEB)

    Siegelman, H W

    1980-01-01

    The photosynthetically-active pigment protein complexes of procaryotes and eucaryotes include chlorophyll proteins, carotenochlorophyll proteins, and biliproteins. They are either integral components or attached to photosynthetic membranes. Detergents are frequently required to solubilize the pigment-protein complexes. The membrane localization and detergent solubilization strongly suggest that the pigment-protein complexes are bound to the membranes by hydrophobic interactions. Hydrophobic interactions of proteins are characterized by an increase in entropy. Their bonding energy is directly related to temperature and ionic strength. Hydrophobic-interaction chromatography, a relatively new separation procedure, can furnish an important method for the purification of pigment-protein complexes. Phycobilisome purification and properties provide an example of the need to maintain hydrophobic interactions to preserve structure and function.

  8. Microsolvation in molecular complexes

    Energy Technology Data Exchange (ETDEWEB)

    Pasquini, M; Schiccheri, N; Piani, G; Pietraperzia, G; Becucci, M; Castellucci, E [European Laboratory for Non-Linear Spectroscopy (LENS), Polo Scientifico e Tecnologico Universita di Firenze, Via Nello Carrara 1, 50019 Sesto Fiorentino (Italy)], E-mail: gianni.pietraperzia@unifi.it

    2008-11-15

    In this paper, we report the results of our study of the microsolvation process involving the anisole molecule. We are able to study bimolecular complexes of different compositions. Changing the second partner molecule bound to anisole, we observed complexes of different geometries, because of the large variety of interactions possible for the anisole. High-resolution electronic spectroscopy is the best tool to reveal the correct vibrationally (zero-point) averaged geometry of the complex. That is done by analysing the rovibronic structure of the electronic spectra, which are related to the equilibrium geometry of the complex as well as dynamical processes, both in the ground and in the excited state. The interpretation of the experimental results is supported by high-level quantum calculations.

  9. Management recommendations: Tewaukon Complex

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This document is a review of land management practices at the Tewaukon Complex, by a land use specialist. Recommendations, time frame and additional comments are...

  10. Complex Strategic Choices

    DEFF Research Database (Denmark)

    Leleur, Steen

    to strategic decision making, Complex Strategic Choices presents a methodology which is further illustrated by a number of case studies and example applications. Dr. Techn. Steen Leleur has adapted previously established research based on feedback and input from various conferences, journals and students...... and students in the field of planning and decision analysis as well as practitioners dealing with strategic analysis and decision making. More broadly, Complex Strategic Choices acts as guide for professionals and students involved in complex planning tasks across several fields such as business....... Complex Strategic Choices provides clear principles and methods which can guide and support strategic decision making to face the many current challenges. By considering ways in which planning practices can be renewed and exploring the possibilities for acquiring awareness and tools to add value...

  11. Doxorubicin Lipid Complex Injection

    Science.gov (United States)

    ... lipid complex is also in combination with another chemotherapy drug to treat multiple myeloma (a type of cancer of the bone marrow) that has not improved or that has worsened after treatment with other ...

  12. Low complexity MIMO receivers

    CERN Document Server

    Bai, Lin; Yu, Quan

    2014-01-01

    Multiple-input multiple-output (MIMO) systems can increase the spectral efficiency in wireless communications. However, the interference becomes the major drawback that leads to high computational complexity at both transmitter and receiver. In particular, the complexity of MIMO receivers can be prohibitively high. As an efficient mathematical tool to devise low complexity approaches that mitigate the interference in MIMO systems, lattice reduction (LR) has been widely studied and employed over the last decade. The co-authors of this book are world's leading experts on MIMO receivers, and here they share the key findings of their research over years. They detail a range of key techniques for receiver design as multiple transmitted and received signals are available. The authors first introduce the principle of signal detection and the LR in mathematical aspects. They then move on to discuss the use of LR in low complexity MIMO receiver design with respect to different aspects, including uncoded MIMO detection...

  13. Supporting complex search tasks

    DEFF Research Database (Denmark)

    Gäde, Maria; Hall, Mark; Huurdeman, Hugo

    2015-01-01

    There is broad consensus in the field of IR that search is complex in many use cases and applications, both on the Web and in domain specific collections, and both professionally and in our daily life. Yet our understanding of complex search tasks, in comparison to simple look up tasks......, is fragmented at best. The workshop addressed the many open research questions: What are the obvious use cases and applications of complex search? What are essential features of work tasks and search tasks to take into account? And how do these evolve over time? With a multitude of information, varying from...... introductory to specialized, and from authoritative to speculative or opinionated, when to show what sources of information? How does the information seeking process evolve and what are relevant differences between different stages? With complex task and search process management, blending searching, browsing...

  14. Beyond complex Langevin equations

    CERN Document Server

    Wosiek, Jacek

    2016-01-01

    A simple integral relation between a complex weight and the corresponding positive distribution is derived by introducing a second complex variable. Together with the positivity and normalizability conditions, this sum rule allows to construct explicitly equivalent pairs of distributions in simple cases. In particular the well known solution for a complex gaussian distribution is generalized to an arbitrary complex slope. This opens a possibility of positive representation of Feynman path integrals directly in the Minkowski time. Such construction is then explicitly carried through in the second part of this presentation. The continuum limit of the new representation exists only if some of the additional couplings tend to infinity and are tuned in a specific way. The approach is then successfully applied to three quantum mechanical examples including a particle in a constant magnetic field -- a simplest prototype of a Wilson line. Further generalizations are shortly discussed and an amusing interpretation of ...

  15. Complex Regional Pain Syndrome

    Science.gov (United States)

    ... leg, such as a crush injury, fracture or amputation. Other major and minor traumas — such as surgery, ... diagnose complex regional pain syndrome, but the following procedures may provide important clues: Bone scan. This procedure ...

  16. Complex Flow Workshop Report

    Energy Technology Data Exchange (ETDEWEB)

    none,

    2012-05-01

    This report documents findings from a workshop on the impacts of complex wind flows in and out of wind turbine environments, the research needs, and the challenges of meteorological and engineering modeling at regional, wind plant, and wind turbine scales.

  17. On scattered subword complexity

    CERN Document Server

    Kása, Zoltán

    2011-01-01

    Special scattered subwords, in which the gaps are of length from a given set, are defined. The scattered subword complexity, which is the number of such scattered subwords, is computed for rainbow words.

  18. Provability, complexity, grammars

    CERN Document Server

    Beklemishev, Lev; Vereshchagin, Nikolai

    1999-01-01

    The book contains English translations of three outstanding dissertations in mathematical logic and complexity theory. L. Beklemishev proves that all provability logics must belong to one of the four previously known classes. The dissertation of M. Pentus proves the Chomsky conjecture about the equivalence of two approaches to formal languages: the Chomsky hierarchy and the Lambek calculus. The dissertation of N. Vereshchagin describes a general framework for criteria of reversability in complexity theory.

  19. Complex variable HVPT

    Energy Technology Data Exchange (ETDEWEB)

    Killingbeck, John P [Mathematics Department, University of Hull, Hull HU6 7RX (United Kingdom); Grosjean, Alain [Laboratoire d' Astrophysique de l' Observatoire de Besancon (CNRS, UPRES-A 6091), 41 bis Avenue de l' Observatoire, BP 1615, 25010 Besancon Cedex (France); Jolicard, Georges [Laboratoire d' Astrophysique de l' Observatoire de Besancon (CNRS, UPRES-A 6091), 41 bis Avenue de l' Observatoire, BP 1615, 25010 Besancon Cedex (France)

    2004-08-13

    Complex variable hypervirial perturbation theory is applied to the case of oscillator and Coulomb potentials perturbed by a single term potential of the form Vx{sup n} or Vr{sup n}, respectively. The trial calculations reported show that this approach can produce accurate complex energies for resonant states via a simple and speedy calculation and can also be useful in studies of PT symmetry and tunnelling resonance effects. (addendum)

  20. Nitrosyl complexes of Technetium

    OpenAIRE

    Ackermann, Janine

    2016-01-01

    The presented thesis describes syntheses and characterization of novel technetium nitrosyl compounds with various ligand systems. The main focus is the synthesis of low-valent technetium nitrosyl complexes with cyclopentadienyl ligands. In the first section, nitrosyltechnetium complexes with monodentate ligands and bidentate P,N chelators are discussed. The established synthetic route for the synthesis of [99mTc(NO)Cl4]- was adopted for the synthesis of this important precursor with the long-...

  1. Advances in network complexity

    CERN Document Server

    Dehmer, Matthias; Emmert-Streib, Frank

    2013-01-01

    A well-balanced overview of mathematical approaches to describe complex systems, ranging from chemical reactions to gene regulation networks, from ecological systems to examples from social sciences. Matthias Dehmer and Abbe Mowshowitz, a well-known pioneer in the field, co-edit this volume and are careful to include not only classical but also non-classical approaches so as to ensure topicality. Overall, a valuable addition to the literature and a must-have for anyone dealing with complex systems.

  2. Uranium hexakisamido complexes

    Energy Technology Data Exchange (ETDEWEB)

    Meyer, K.; Mindiola, D.J.; Baker, T.A.; Davis, W.M.; Cummins, C.C. [Massachusetts Inst. of Tech., Cambridge, MA (United States). Dept. of Chemistry

    2000-09-01

    Minimal structural changes accompany the oxidation of the paramagnetic uranium(V) anion [U(dbabh){sub 6}]{sup -} to the neutral, diamagnetic counterpart [U(dbabh){sub 6}] (see structure). These two T{sub h}-stmmetric complexes, which were synthetized starting from 2,3:5,6-dibenzo-7-azabicyclo[2.2.1]hepta-2,5-diene (Hdbabh), are the first isolable homoleptic hexakisamido complexes of uranium(V) and (VI). (orig.)

  3. Urban geography and complexity

    Directory of Open Access Journals (Sweden)

    Denise Pumain

    2004-12-01

    Full Text Available The contemporary approach of complex systems raises common questions that could be handled by a transdisciplinary theory. We demonstrate how the main concepts of urban geography could be integrated in such a theory ofcomplexity. We illustrate the complexity approach by a short presentationof the SIMPOP model that uses a multi-agents formalism for the simulationof the evolutionary properties of systems of cities.

  4. Algorithmic Relative Complexity

    OpenAIRE

    Daniele Cerra; Mihai Datcu

    2011-01-01

    Information content and compression are tightly related concepts that can be addressed through both classical and algorithmic information theories, on the basis of Shannon entropy and Kolmogorov complexity, respectively. The definition of several entities in Kolmogorov’s framework relies upon ideas from classical information theory, and these two approaches share many common traits. In this work, we expand the relations between these two frameworks by introducing algorithmic cross-complexity ...

  5. Electrospun complexes - functionalised nanofibres

    Energy Technology Data Exchange (ETDEWEB)

    Meyer, T.; Wolf, M.; Dreyer, B.; Unruh, D.; Krüger, C.; Menze, M. [Leibniz University Hannover, Institute of Inorganic Chemistry (Germany); Sindelar, R. [University of Applied Science Hannover, Faculty II (Germany); Klingelhöfer, G. [Gutenberg-University, Institute of Inorganic and Analytic Chemistry (Germany); Renz, F., E-mail: renz@acd.uni-hannover.de [Leibniz University Hannover, Institute of Inorganic Chemistry (Germany)

    2016-12-15

    Here we present a new approach of using iron-complexes in electro-spun fibres. We modify poly(methyl methacrylate) (PMMA) by replacing the methoxy group with Diaminopropane or Ethylenediamine. The complex is bound covalently via an imine-bridge or an amide. The resulting polymer can be used in the electrospinning process without any further modifications in method either as pure reagent or mixed with small amounts of not functionalised polymer resulting in fibres of different qualities (Fig. 1).

  6. Quantum Hamiltonian Complexity

    OpenAIRE

    Gharibian, Sevag; Huang, Yichen; Landau, Zeph; Shin, Seung Woo

    2014-01-01

    Constraint satisfaction problems are a central pillar of modern computational complexity theory. This survey provides an introduction to the rapidly growing field of Quantum Hamiltonian Complexity, which includes the study of quantum constraint satisfaction problems. Over the past decade and a half, this field has witnessed fundamental breakthroughs, ranging from the establishment of a "Quantum Cook-Levin Theorem" to deep insights into the structure of 1D low-temperature quantum systems via s...

  7. Complex fate of paralogs

    Directory of Open Access Journals (Sweden)

    Snel Berend

    2008-12-01

    Full Text Available Abstract Background Thanks to recent high coverage mass-spectrometry studies and reconstructed protein complexes, we are now in an unprecedented position to study the evolution of biological systems. Gene duplications, known to be a major source of innovation in evolution, can now be readily examined in the context of protein complexes. Results We observe that paralogs operating in the same complex fulfill different roles: mRNA dosage increase for more than a hundred cytosolic ribosomal proteins, mutually exclusive participation of at least 54 paralogs resulting in alternative forms of complexes, and 24 proteins contributing to bona fide structural growth. Inspection of paralogous proteins participating in two independent complexes shows that an ancient, pre-duplication protein functioned in both multi-protein assemblies and a gene duplication event allowed the respective copies to specialize and split their roles. Conclusion Variants with conditionally assembled, paralogous subunits likely have played a role in yeast's adaptation to anaerobic conditions. In a number of cases the gene duplication has given rise to one duplicate that is no longer part of a protein complex and shows an accelerated rate of evolution. Such genes could provide the raw material for the evolution of new functions.

  8. Complex fate of paralogs.

    Science.gov (United States)

    Szklarczyk, Radek; Huynen, Martijn A; Snel, Berend

    2008-12-18

    Thanks to recent high coverage mass-spectrometry studies and reconstructed protein complexes, we are now in an unprecedented position to study the evolution of biological systems. Gene duplications, known to be a major source of innovation in evolution, can now be readily examined in the context of protein complexes. We observe that paralogs operating in the same complex fulfill different roles: mRNA dosage increase for more than a hundred cytosolic ribosomal proteins, mutually exclusive participation of at least 54 paralogs resulting in alternative forms of complexes, and 24 proteins contributing to bona fide structural growth. Inspection of paralogous proteins participating in two independent complexes shows that an ancient, pre-duplication protein functioned in both multi-protein assemblies and a gene duplication event allowed the respective copies to specialize and split their roles. Variants with conditionally assembled, paralogous subunits likely have played a role in yeast's adaptation to anaerobic conditions. In a number of cases the gene duplication has given rise to one duplicate that is no longer part of a protein complex and shows an accelerated rate of evolution. Such genes could provide the raw material for the evolution of new functions.

  9. MANAGEMENT OF SPORT COMPLEXES

    Directory of Open Access Journals (Sweden)

    Marian STAN

    2015-07-01

    Full Text Available The actuality of the investigated theme. Nowadays, human evolution, including his intellectual development, proves the fact that especially the creation manpower and the employment was the solution of all life’s ambitions in society. So, the fact is that in reality, man is the most important capital of the society. Also, in an individual’s life, the practice of sport plays a significant role and that’s why the initiation, the launch and the management of sports complexes activity reveal the existence of specific management features that we will identify and explain in the current study. The aim of the research refers to the elaboration of a theoretical base of the management of the sport complexes, to the pointing of the factors that influence the efficient existence and function of a sport complex in our country and to the determination of the responsibilities that have a manager who directs successfully the activity of the sport complexes. The investigation is based on theoretical methods, such as: scientific documentation, analysis, synthesis, comparison and on empirical research methods, like: study of researched literature and observation. The results of the research indicate the fact that the profitability of a sport complex must assure a particular structure to avoid the bankruptcy risk and also, that the administration of the sport complexes activity must keep in view the reliable functions of the contemporaneous management.

  10. Cell complexes through time

    Science.gov (United States)

    Klette, Reinhard

    2000-10-01

    The history of cell complexes is closely related to the birth and development of topology in general. Johann Benedict Listing (1802 - 1882) introduced the term 'topology' into mathematics in a paper published in 1847, and he also defined cell complexes for the first time in a paper published in 1862. Carl Friedrich Gauss (1777 - 1855) is often cited as the one who initiated these ideas, but he did not publish either on topology or on cell complexes. The pioneering work of Leonhard Euler (1707 - 1783) on graphs is also often cited as the birth of topology, and Euler's work was cited by Listing in 1862 as a stimulus for his research on cell complexes. There are different branches in topology which have little in common: point set topology, algebraic topology, differential topology etc. Confusion may arise if just 'topology' is specified, without clarifying the used concept. Topological subjects in mathematics are often related to continuous models, and therefore quite irrelevant to computer based solutions in image analysis. Compared to this, only a minority of topology publications in mathematics addresses discrete spaces which are appropriate for computer-based image analysis. In these cases, often the notion of a cell complex plays a crucial role. This paper briefly reports on a few of these publications. This paper is not intended to cover the very lively progress in cell complex studies within the context of image analysis during the last two decades. Basically it stops its historic review at the time when this subject in image analysis research gained speed in 1980 - 1990. As a general point of view, the paper indicates that image analysis contributes to a fusion of topological concepts, the geometric and the abstract cell structure approach and point set topology, which may lead towards new problems for the study of topologies defined on geometric or abstract cell complexes.

  11. Turbulent complex (dusty) plasma

    Science.gov (United States)

    Zhdanov, Sergey; Schwabe, Mierk

    2017-04-01

    As a paradigm of complex system dynamics, solid particles immersed into a weakly ionized plasma, so called complex (dusty) plasmas, were (and continue to be) a subject of many detailed studies. Special types of dynamical activity have been registered, in particular, spontaneous pairing, entanglement and cooperative action of a great number of particles resulting in formation of vortices, self-propelling, tunneling, and turbulent movements. In the size domain of 1-10 mkm normally used in experiments with complex plasmas, the characteristic dynamic time-scale is of the order of 0.01-0.1 s, and these particles can be visualized individually in real time, providing an atomistic (kinetic) level of investigations. The low-R turbulent flow induced either by the instability in a complex plasma cloud or formed behind a projectile passing through the cloud is a typical scenario. Our simulations showed formation of a fully developed system of vortices and demonstrated that the velocity structure functions scale very close to the theoretical predictions. As an important element of self-organization, cooperative and turbulent particle motions are present in many physical, astrophysical, and biological systems. Therefore, experiments with turbulent wakes and turbulent complex plasma oscillations are a promising mean to observe and study in detail the anomalous transport on the level of individual particles.

  12. Complexity: The bigger picture

    CERN Document Server

    Vicsek, Tamás

    2010-01-01

    If a concept is not well defined, there are grounds for its abuse. This is particularly true of complexity, an inherently interdisciplinary concept that has penetrated very different fields of intellectual activity from physics to linguistics, but with no underlying, unified theory. Complexity has become a popular buzzword used in the hope of gaining attention or funding -- institutes and research networks associated with complex systems grow like mushrooms. Why and how did it happen that this vague notion has become a central motif in modern science? Is it only a fashion, a kind of sociological phenomenon, or is it a sign of a changing paradigm of our perception of the laws of nature and of the approaches required to understand them? Because virtually every real system is inherently extremely complicated, to say that a system is complex is almost an empty statement - couldn't an Institute of Complex Systems just as well be called an Institute for Almost Everything? Despite these valid concerns, the world is ...

  13. Controllability of Complex Networks

    Science.gov (United States)

    Liu, Yang; Slotine, Jean-Jacques; Barabasi, Albert-Laszlo

    2011-03-01

    The ultimate proof of our understanding of natural or technological systems is reflected in our ability to control them. While control theory offers mathematical tools to steer engineered systems towards a desired state, we lack a general framework to control complex self-organized systems, like the regulatory network of a cell or the Internet. Here we develop analytical tools to study the controllability of an arbitrary complex directed network, identifying the set of driver nodes whose time-dependent control can guide the system's dynamics. We apply these tools to real and model networks, finding that sparse inhomogeneous networks, which emerge in many real complex systems, are the most difficult to control. In contrast, dense and homogeneous networks can be controlled via a few driver nodes. Counterintuitively, we find that in both model and real systems the driver nodes tend to avoid the hubs. We show that the robustness of control to link failure is determined by a core percolation problem, helping us understand why many complex systems are relatively insensitive to link deletion. The developed approach offers a framework to address the controllability of an arbitrary network, representing a key step towards the eventual control of complex systems.

  14. Algorithmic Relative Complexity

    Directory of Open Access Journals (Sweden)

    Daniele Cerra

    2011-04-01

    Full Text Available Information content and compression are tightly related concepts that can be addressed through both classical and algorithmic information theories, on the basis of Shannon entropy and Kolmogorov complexity, respectively. The definition of several entities in Kolmogorov’s framework relies upon ideas from classical information theory, and these two approaches share many common traits. In this work, we expand the relations between these two frameworks by introducing algorithmic cross-complexity and relative complexity, counterparts of the cross-entropy and relative entropy (or Kullback-Leibler divergence found in Shannon’s framework. We define the cross-complexity of an object x with respect to another object y as the amount of computational resources needed to specify x in terms of y, and the complexity of x related to y as the compression power which is lost when adopting such a description for x, compared to the shortest representation of x. Properties of analogous quantities in classical information theory hold for these new concepts. As these notions are incomputable, a suitable approximation based upon data compression is derived to enable the application to real data, yielding a divergence measure applicable to any pair of strings. Example applications are outlined, involving authorship attribution and satellite image classification, as well as a comparison to similar established techniques.

  15. Reconciling Ligase Ribozyme Activity with Fatty Acid Vesicle Stability

    NARCIS (Netherlands)

    Anella, F.; Danelon, C.

    2014-01-01

    The “RNA world” and the “Lipid world” theories for the origin of cellular life are often considered incompatible due to the differences in the environmental conditions at which they can emerge. One obstacle resides in the conflicting requirements for divalent metal ions, in particular Mg2+, with

  16. Electronic Structure Rearrangements in Hybrid Ribozyme/Protein Catalysis

    Science.gov (United States)

    Kang, Jiyoung; Kino, Hiori; Field, Martin J.; Tateno, Masaru

    2017-04-01

    We analyzed the electronic structural changes that occur in the reaction cycle of a biological catalyst composed of RNA and protein, and elucidated the dynamical rearrangements of the electronic structure that was obtained from our previous study in which ab initio quantum mechanics/molecular mechanics molecular dynamics simulations were performed. Notable results that we obtained include the generation of a reactive HOMO that is responsible for bond formation in the initial stages of the reaction, and the appearance of a reactive LUMO that is involved in the bond rupture that leads to products. We denote these changes as dynamical induction of the reactive HOMO (DIRH) and LUMO (DIRL), respectively. Interestingly, we also find that the induction of the reactive HOMO is enhanced by the formation of a low-barrier hydrogen bond (LBHB), which, to the best of our knowledge, represents a novel role for LBHBs in enzymatic systems.

  17. Tuberous sclerosis complex

    Directory of Open Access Journals (Sweden)

    Alexander Jerman

    2014-05-01

    Full Text Available Tuberous sclerosis complex is a genetic disorder with a characteristic development of a benign tumorous growth in various tissues. Clinical picture is very heterogeneous, resulting in difficult diagnosis and unrecognized patients. In this article, we present pathophysiological basis for understanding the clinical picture and the diagnosis of tuberous sclerosis complex. The skin, central nervous system, kidneys and heart are the most commonly affected sites. The disease course is progressive. Although the great majority of lesions are benign, life expectancy and quality of life are affected by their secondary impact. Until recently, the therapy has been only symptomatic, but nowadays the inhibitors of mTOR complex, such as everolimus, are efficient in reducing the growth of tumors.

  18. Synchronization in complex networks

    Energy Technology Data Exchange (ETDEWEB)

    Arenas, A.; Diaz-Guilera, A.; Moreno, Y.; Zhou, C.; Kurths, J.

    2007-12-12

    Synchronization processes in populations of locally interacting elements are in the focus of intense research in physical, biological, chemical, technological and social systems. The many efforts devoted to understand synchronization phenomena in natural systems take now advantage of the recent theory of complex networks. In this review, we report the advances in the comprehension of synchronization phenomena when oscillating elements are constrained to interact in a complex network topology. We also overview the new emergent features coming out from the interplay between the structure and the function of the underlying pattern of connections. Extensive numerical work as well as analytical approaches to the problem are presented. Finally, we review several applications of synchronization in complex networks to different disciplines: biological systems and neuroscience, engineering and computer science, and economy and social sciences.

  19. Large erupted complex odontoma

    Directory of Open Access Journals (Sweden)

    Vijeev Vasudevan

    2009-01-01

    Full Text Available Odontomas are a heterogeneous group of jaw bone lesions, classified as odontogenic tumors which usually include well-diversified dental tissues. Odontoma is a term introduced to the literature by Broca in 1867. Trauma, infection and hereditary factors are the possible causes of forming this kind of lesions. Among odontogenic tumors, they constitute about 2/3 of cases. These lesions usually develop slowly and asymptomatically, and in most cases they do not cross the bone borders. Two types of odontoma are recognized: compound and complex. Complex odontomas are less common than the compound variety in the ratio 1:2.3. Eruption of an odontoma in the oral cavity is rare. We present a case of complex odontoma, in which apparent eruption has occurred in the area of the right maxillary second molar region.

  20. Philosophy of complex systems

    CERN Document Server

    2011-01-01

    The domain of nonlinear dynamical systems and its mathematical underpinnings has been developing exponentially for a century, the last 35 years seeing an outpouring of new ideas and applications and a concomitant confluence with ideas of complex systems and their applications from irreversible thermodynamics. A few examples are in meteorology, ecological dynamics, and social and economic dynamics. These new ideas have profound implications for our understanding and practice in domains involving complexity, predictability and determinism, equilibrium, control, planning, individuality, responsibility and so on. Our intention is to draw together in this volume, we believe for the first time, a comprehensive picture of the manifold philosophically interesting impacts of recent developments in understanding nonlinear systems and the unique aspects of their complexity. The book will focus specifically on the philosophical concepts, principles, judgments and problems distinctly raised by work in the domain of comple...

  1. Modeling Complex Systems

    CERN Document Server

    Boccara, Nino

    2010-01-01

    Modeling Complex Systems, 2nd Edition, explores the process of modeling complex systems, providing examples from such diverse fields as ecology, epidemiology, sociology, seismology, and economics. It illustrates how models of complex systems are built and provides indispensable mathematical tools for studying their dynamics. This vital introductory text is useful for advanced undergraduate students in various scientific disciplines, and serves as an important reference book for graduate students and young researchers. This enhanced second edition includes: . -recent research results and bibliographic references -extra footnotes which provide biographical information on cited scientists who have made significant contributions to the field -new and improved worked-out examples to aid a student’s comprehension of the content -exercises to challenge the reader and complement the material Nino Boccara is also the author of Essentials of Mathematica: With Applications to Mathematics and Physics (Springer, 2007).

  2. Can Complexity be Planned?

    Directory of Open Access Journals (Sweden)

    Ilona Koutny

    2015-04-01

    Full Text Available The long accepted complexity invariance of human languages has become controversial within the last decade. In investigations of the problem, both creole and planned languages have often been neglected. After a presentation of the scope of the invariance problem and the proposition of the natural to planned language continuum, this article will discuss the contribution of planned languages. It will analyze the complexity of Esperanto at the phonological, morphological, syntactic and semantic levels, using linguistic data bases. The role of the L2 speech community and development of the language will also be taken into account when discussing the endurance of the same level of simplicity of this planned international language. The author argues that complexity can be variable and to some extent planned and maintained.

  3. Complex Strategic Choices

    DEFF Research Database (Denmark)

    Leleur, Steen

    to strategic decision making, Complex Strategic Choices presents a methodology which is further illustrated by a number of case studies and example applications. Dr. Techn. Steen Leleur has adapted previously established research based on feedback and input from various conferences, journals and students......Effective decision making requires a clear methodology, particularly in a complex world of globalisation. Institutions and companies in all disciplines and sectors are faced with increasingly multi-faceted areas of uncertainty which cannot always be effectively handled by traditional strategies....... Complex Strategic Choices provides clear principles and methods which can guide and support strategic decision making to face the many current challenges. By considering ways in which planning practices can be renewed and exploring the possibilities for acquiring awareness and tools to add value...

  4. Simulation in Complex Modelling

    DEFF Research Database (Denmark)

    Nicholas, Paul; Ramsgaard Thomsen, Mette; Tamke, Martin

    2017-01-01

    This paper will discuss the role of simulation in extended architectural design modelling. As a framing paper, the aim is to present and discuss the role of integrated design simulation and feedback between design and simulation in a series of projects under the Complex Modelling framework. Complex...... performance, engage with high degrees of interdependency and allow the emergence of design agency and feedback between the multiple scales of architectural construction. This paper presents examples for integrated design simulation from a series of projects including Lace Wall, A Bridge Too Far and Inflated...... Restraint developed for the research exhibition Complex Modelling, Meldahls Smedie Gallery, Copenhagen in 2016. Where the direct project aims and outcomes have been reported elsewhere, the aim for this paper is to discuss overarching strategies for working with design integrated simulation....

  5. Modeling Complex Time Limits

    Directory of Open Access Journals (Sweden)

    Oleg Svatos

    2013-01-01

    Full Text Available In this paper we analyze complexity of time limits we can find especially in regulated processes of public administration. First we review the most popular process modeling languages. There is defined an example scenario based on the current Czech legislature which is then captured in discussed process modeling languages. Analysis shows that the contemporary process modeling languages support capturing of the time limit only partially. This causes troubles to analysts and unnecessary complexity of the models. Upon unsatisfying results of the contemporary process modeling languages we analyze the complexity of the time limits in greater detail and outline lifecycles of a time limit using the multiple dynamic generalizations pattern. As an alternative to the popular process modeling languages there is presented PSD process modeling language, which supports the defined lifecycles of a time limit natively and therefore allows keeping the models simple and easy to understand.

  6. Introduction to Complex Plasmas

    CERN Document Server

    Bonitz, Michael; Ludwig, Patrick

    2010-01-01

    Complex plasmas differ from traditional plasmas in many ways: these are low-temperature high pressure systems containing nanometer to micrometer size particles which may be highly charged and strongly interacting. The particles may be chemically reacting or be in contact with solid surfaces, and the electrons may show quantum behaviour. These interesting properties have led to many applications of complex plasmas in technology, medicine and science. Yet complex plasmas are extremely complicated, both experimentally and theoretically, and require a variety of new approaches which go beyond standard plasma physics courses. This book fills this gap presenting an introduction to theory, experiment and computer simulation in this field. Based on tutorial lectures at a very successful recent Summer Institute, the presentation is ideally suited for graduate students, plasma physicists and experienced undergraduates.

  7. Complex function theory

    CERN Document Server

    Sarason, Donald

    2007-01-01

    Complex Function Theory is a concise and rigorous introduction to the theory of functions of a complex variable. Written in a classical style, it is in the spirit of the books by Ahlfors and by Saks and Zygmund. Being designed for a one-semester course, it is much shorter than many of the standard texts. Sarason covers the basic material through Cauchy's theorem and applications, plus the Riemann mapping theorem. It is suitable for either an introductory graduate course or an undergraduate course for students with adequate preparation. The first edition was published with the title Notes on Co

  8. Luminescent macrocyclic lanthanide complexes

    Science.gov (United States)

    Raymond, Kenneth N [Berkeley, CA; Corneillie, Todd M [Campbell, CA; Xu, Jide [Berkeley, CA

    2012-05-08

    The present invention provides a novel class of macrocyclic compounds as well as complexes formed between a metal (e.g., lanthanide) ion and the compounds of the invention. Preferred complexes exhibit high stability as well as high quantum yields of lanthanide ion luminescence in aqueous media without the need for secondary activating agents. Preferred compounds incorporate hydroxy-isophthalamide moieties within their macrocyclic structure and are characterized by surprisingly low, non-specific binding to a variety of polypeptides such as antibodies and proteins as well as high kinetic stability. These characteristics distinguish them from known, open-structured ligands.

  9. Complex HVPT and hyperasymptotics

    Energy Technology Data Exchange (ETDEWEB)

    Killingbeck, John P [Mathematics Department, University of Hull, Hull HU6 7RX (United Kingdom); Grosjean, Alain [Laboratoire d' Astrophysique de l' Observatoire de Besancon(CNRS, UMR 6091), 41 bis Avenue de l' Observatoire, BP 1615, 25010 Besancon Cedex (France); Jolicard, Georges [Laboratoire d' Astrophysique de l' Observatoire de Besancon(CNRS, UMR 6091), 41 bis Avenue de l' Observatoire, BP 1615, 25010 Besancon Cedex (France)

    2006-08-25

    Complex hypervirial perturbation theory (HVPT) is applied to the problem of a harmonic oscillator with a perturbation gx{sup 3}exp(i{psi}), for which the traditional Rayleigh-Schodinger perturbation theory has to be supplemented by hyperasymptotics for obtaining accurate resonance energies in the negative {psi} region. Complex HVPT gives accurate results for positive {psi} and for negative {psi} up to about vertical bar {phi} vertical bar = {pi}/24. The case of a quartic perturbed oscillator is also treated. (letter to the editor)

  10. Complexity, time and music

    OpenAIRE

    JEAN PIERRE BOON

    2009-01-01

    The concept of complexity as considered in terms of its algorithmic definition proposed by G.J. Chaitin and A.N. Kolmogorov is revisited for the dynamical complexity of music. When music pieces are cast in the form of time series of pitch variations, concepts of dynamical systems theory can be used to define new quantities such as the {\\em dimensionality} as a measure of the {\\em global temporal dynamics} of a music piece, and the Shanon {\\em entropy} as an evaluation of its {\\em local dynami...

  11. Complex matrix model duality

    Energy Technology Data Exchange (ETDEWEB)

    Brown, T.W.

    2010-11-15

    The same complex matrix model calculates both tachyon scattering for the c=1 non-critical string at the self-dual radius and certain correlation functions of half-BPS operators in N=4 super- Yang-Mills. It is dual to another complex matrix model where the couplings of the first model are encoded in the Kontsevich-like variables of the second. The duality between the theories is mirrored by the duality of their Feynman diagrams. Analogously to the Hermitian Kontsevich- Penner model, the correlation functions of the second model can be written as sums over discrete points in subspaces of the moduli space of punctured Riemann surfaces. (orig.)

  12. Nonlinear dynamics and complexity

    CERN Document Server

    Luo, Albert; Fu, Xilin

    2014-01-01

    This important collection presents recent advances in nonlinear dynamics including analytical solutions, chaos in Hamiltonian systems, time-delay, uncertainty, and bio-network dynamics. Nonlinear Dynamics and Complexity equips readers to appreciate this increasingly main-stream approach to understanding complex phenomena in nonlinear systems as they are examined in a broad array of disciplines. The book facilitates a better understanding of the mechanisms and phenomena in nonlinear dynamics and develops the corresponding mathematical theory to apply nonlinear design to practical engineering.

  13. Complex logistics audit system

    Directory of Open Access Journals (Sweden)

    Zuzana Marková

    2010-02-01

    Full Text Available Complex logistics audit system is a tool for realization of logistical audit in the company. The current methods for logistics auditare based on “ad hok” analysis of logisticsl system. This paper describes system for complex logistics audit. It is a global diagnosticsof logistics processes and functions of enterprise. The goal of logistics audit is to provide comparative documentation for managementabout state of logistics in company and to show the potential of logistics changes in order to achieve more effective companyperformance.

  14. Theories of computational complexity

    CERN Document Server

    Calude, C

    1988-01-01

    This volume presents four machine-independent theories of computational complexity, which have been chosen for their intrinsic importance and practical relevance. The book includes a wealth of results - classical, recent, and others which have not been published before.In developing the mathematics underlying the size, dynamic and structural complexity measures, various connections with mathematical logic, constructive topology, probability and programming theories are established. The facts are presented in detail. Extensive examples are provided, to help clarify notions and constructions. The lists of exercises and problems include routine exercises, interesting results, as well as some open problems.

  15. Applied complex variables

    CERN Document Server

    Dettman, John W

    1965-01-01

    Analytic function theory is a traditional subject going back to Cauchy and Riemann in the 19th century. Once the exclusive province of advanced mathematics students, its applications have proven vital to today's physicists and engineers. In this highly regarded work, Professor John W. Dettman offers a clear, well-organized overview of the subject and various applications - making the often-perplexing study of analytic functions of complex variables more accessible to a wider audience. The first half of Applied Complex Variables, designed for sequential study, is a step-by-step treatment of fun

  16. Introduction to complex analysis

    CERN Document Server

    Priestley, H A

    2003-01-01

    Complex analysis is a classic and central area of mathematics, which is studied and exploited in a range of important fields, from number theory to engineering. Introduction to Complex Analysis was first published in 1985, and for this much awaited second edition the text has been considerably expanded, while retaining the style of the original. More detailed presentation is given of elementary topics, to reflect the knowledge base of current students. Exercise sets have beensubstantially revised and enlarged, with carefully graded exercises at the end of each chapter.This is the latest additi

  17. Complex variables II essentials

    CERN Document Server

    Solomon, Alan D

    2013-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Complex Variables II includes elementary mappings and Mobius transformation, mappings by general functions, conformal mappings and harmonic functions, applying complex functions to a

  18. Entropy, Search, Complexity

    CERN Document Server

    Katona, Gyula O H; Tardos, Gábor

    2007-01-01

    The present volume is a collection of survey papers in the fields of entropy, search and complexity. They summarize the latest developments in their respective areas. More than half of the papers belong to search theory which lies on the borderline of mathematics and computer science, information theory and combinatorics, respectively. Search theory has variegated applications, among others in bioinformatics. Some of these papers also have links to linear statistics and communicational complexity. Further works survey the fundamentals of information theory and quantum source coding. The volume is recommended to experienced researchers as well as young scientists and students both in mathematics and computer science

  19. Complex Regional Pain Syndrome

    Science.gov (United States)

    Complex regional pain syndrome (CRPS) is a chronic pain condition. It causes intense pain, usually in the arms, hands, legs, or feet. It may happen ... move the affected body part The cause of CRPS is unknown. There is no specific diagnostic test. ...

  20. Complex fate of paralogs

    NARCIS (Netherlands)

    Szklarczyk, R.; Huynen, M.A.; Snel, B.

    2008-01-01

    BACKGROUND: Thanks to recent high coverage mass-spectrometry studies and reconstructed protein complexes, we are now in an unprecedented position to study the evolution of biological systems. Gene duplications, known to be a major source of innovation in evolution, can now be readily examined in the

  1. Symmetry in Complex Networks

    Directory of Open Access Journals (Sweden)

    Angel Garrido

    2011-01-01

    Full Text Available In this paper, we analyze a few interrelated concepts about graphs, such as their degree, entropy, or their symmetry/asymmetry levels. These concepts prove useful in the study of different types of Systems, and particularly, in the analysis of Complex Networks. A System can be defined as any set of components functioning together as a whole. A systemic point of view allows us to isolate a part of the world, and so, we can focus on those aspects that interact more closely than others. Network Science analyzes the interconnections among diverse networks from different domains: physics, engineering, biology, semantics, and so on. Current developments in the quantitative analysis of Complex Networks, based on graph theory, have been rapidly translated to studies of brain network organization. The brain's systems have complex network features—such as the small-world topology, highly connected hubs and modularity. These networks are not random. The topology of many different networks shows striking similarities, such as the scale-free structure, with the degree distribution following a Power Law. How can very different systems have the same underlying topological features? Modeling and characterizing these networks, looking for their governing laws, are the current lines of research. So, we will dedicate this Special Issue paper to show measures of symmetry in Complex Networks, and highlight their close relation with measures of information and entropy.

  2. pyridine-carboxamide complexes

    Indian Academy of Sciences (India)

    cadmium ions, but in different coordination environments, depending on the counter anion used. In addition, electronic absorption, fluorescence spectroscopy and viscosity measurements revealed a significant interaction of the four complexes with .... Data collection, data reduction, structure solu- tion/refinement were ...

  3. Surface complexation modeling

    Science.gov (United States)

    Adsorption-desorption reactions are important processes that affect the transport of contaminants in the environment. Surface complexation models are chemical models that can account for the effects of variable chemical conditions, such as pH, on adsorption reactions. These models define specific ...

  4. unsymmetrical Schiff base complexes

    Indian Academy of Sciences (India)

    The kinetics of thermal decomposition was stud- ied using thermal gravimetric method (TG) and Coats-Redfern equation. According to Coats-Redfern plots, the kinetics of thermal decomposition of the studied complexes is first-order in all stages. Also the kinetics and mechanism of the exchange reaction of the coordinated ...

  5. Life: Complexity and Diversity

    Indian Academy of Sciences (India)

    are rewarded by flowering plants with nectar and superabundant pollen for the services of pollination rendered by them. As living organisms have adopted these newer ways of life and invaded an ever greater range of habitats, they have assumed larger sizes and more complex structures (Figure 2). Bacteria subsisting as ...

  6. schiff base complexes

    African Journals Online (AJOL)

    DR. AMINU

    ABSTRACT. The complexes of iron (II) and nickel (II) with schiff base derived from benzoin and 2-amino benzoic acid have been prepared. Solubility, melting point, decomposition temperature, conductance measurement, infrared (IR) and UV – Visible spectrophotometric studies were used in characterizing the compounds.

  7. Complexity driven photonics

    KAUST Repository

    Fratalocchi, Andrea

    2014-12-01

    Disorder and chaos are ubiquitous phenomena that are mostly unwanted in applications. On the contrary, they can be exploited to create a new technology. In this talk I will summarize my research in this field, discussing chaotic energy harvesting, nonlinear stochastic resonance and complex nanolasers.

  8. Prediction of Biomolecular Complexes

    KAUST Repository

    Vangone, Anna

    2017-04-12

    Almost all processes in living organisms occur through specific interactions between biomolecules. Any dysfunction of those interactions can lead to pathological events. Understanding such interactions is therefore a crucial step in the investigation of biological systems and a starting point for drug design. In recent years, experimental studies have been devoted to unravel the principles of biomolecular interactions; however, due to experimental difficulties in solving the three-dimensional (3D) structure of biomolecular complexes, the number of available, high-resolution experimental 3D structures does not fulfill the current needs. Therefore, complementary computational approaches to model such interactions are necessary to assist experimentalists since a full understanding of how biomolecules interact (and consequently how they perform their function) only comes from 3D structures which provide crucial atomic details about binding and recognition processes. In this chapter we review approaches to predict biomolecular complexesBiomolecular complexes, introducing the concept of molecular dockingDocking, a technique which uses a combination of geometric, steric and energetics considerations to predict the 3D structure of a biological complex starting from the individual structures of its constituent parts. We provide a mini-guide about docking concepts, its potential and challenges, along with post-docking analysis and a list of related software.

  9. Conversation, coupling and complexity

    DEFF Research Database (Denmark)

    Fusaroli, Riccardo; Abney, Drew; Bahrami, Bahador

    We investigate the linguistic co-construction of interpersonal synergies. By applying a measure of coupling between complex systems to an experimentally elicited corpus of joint decision dialogues, we show that interlocutors’ linguistic behavior displays increasing signature of multi-scale coupli...

  10. Automatic Complexity Analysis

    DEFF Research Database (Denmark)

    Rosendahl, Mads

    1989-01-01

    One way to analyse programs is to to derive expressions for their computational behaviour. A time bound function (or worst-case complexity) gives an upper bound for the computation time as a function of the size of input. We describe a system to derive such time bounds automatically using abstract...

  11. Debating complexity in modeling

    Science.gov (United States)

    Hunt, Randall J.; Zheng, Chunmiao

    1999-01-01

    Complexity in modeling would seem to be an issue of universal importance throughout the geosciences, perhaps throughout all science, if the debate last year among groundwater modelers is any indication. During the discussion the following questions and observations made up the heart of the debate.

  12. The CERN accelerator complex

    CERN Multimedia

    Mobs, Esma Anais

    2016-01-01

    The LHC is the last ring (dark blue line) in a complex chain of particle accelerators. The smaller machines are used in a chain to help boost the particles to their final energies and provide beams to a whole set of smaller experiments, which also aim to uncover the mysteries of the Universe.

  13. The CERN accelerator complex

    CERN Multimedia

    Haffner, Julie

    2013-01-01

    The LHC is the last ring (dark grey line) in a complex chain of particle accelerators. The smaller machines are used in a chain to help boost the particles to their final energies and provide beams to a whole set of smaller experiments, which also aim to uncover the mysteries of the Universe.

  14. Psychopathology and complexity

    Directory of Open Access Journals (Sweden)

    Leonardo Y. Álvarez R

    2010-08-01

    Full Text Available The paradigm of complexity states that reality conveys a chaotic dynamics, ambiguous, blurred, and paradoxical, and that it does not fulfill the values of order, harmony nor perfection. However, such a chaos represents a specific way of organization and order. Human behavior explained by this paradigm vindicates on this way the outstanding role of contradiction and irregularity aside of what is linear and predictable. The purpose of this review has the primary aim to describe some concepts and assumptions that give support to the approach to complexity in behavior, especially concerning the psychopathological behavior of an individual. Some comparisons with concepts associated to complexity in scientific approaches to psychology (contextual and paradigmatical behaviorism and interbehaviorism from its own persepctive are stablished. All these elements are developed underlining the concepts of reciprocal multicausality, complex and hierarchical learning, historical and contextual factors in the comprehension of behavior, and trying to make some extrapolations on the psychopathological behavior. This approach is hence considered appropriate and necessary to understand gnosiological entities and to intervene them in their role of clinical challenges.

  15. The CERN accelerator complex

    CERN Multimedia

    Christiane Lefèvre

    2008-01-01

    The LHC is the last ring (dark grey line) in a complex chain of particle accelerators. The smaller machines are used in a chain to help boost the particles to their final energies and provide beams to a whole set of smaller experiments, which also aim to uncover the mysteries of the Universe.

  16. Tevatron's complex collider cousins

    CERN Multimedia

    Fischer, W

    2004-01-01

    Letter referring to Schwarzschild's story "Disappointing performance and tight budgets confront Fermilab with tough decisions" and contesting that the Tevatron is not the most complex accelerator operating. They use the examples of CERN's SPS collider, HERA at DESY and the RHIC at Brookhaven (1/4 page)

  17. Architecture of Glaciotectonic Complexes

    Directory of Open Access Journals (Sweden)

    Stig A. Schack Pedersen

    2014-10-01

    Full Text Available Glaciotectonic studies are an integrated part of the Quaternary geological research carried out by the Danish geological survey. Almost all the hilly areas in Denmark were created or affected by glaciotectonic deformations, and the features are included in the mapping of surface near deposits. For the mapping and support of constructing 3D geological models a classification of architecture of glaciotectonic complexes is suggested. The important elements for classification of architecture are the surfaces. Four orders of surfaces are defined for glaciotectonic complexes: first-order surfaces are décollement surfaces and glaciotectonic unconformities; second-order surfaces are ramps and flats—the thrust faults; third-order surfaces are folded beds—anticlines and synclines; and fourth-order surfaces are small scale folds and faults—kink bands, conjugate faults, box folds, etc. The most important first-order surface is the décollement surface. This surface limits the glaciotectonic complex at its base and controls the extent of glaciotectonic disturbances. Below this surface, ordinary flat lying planar bedding occurs, whereas above the surface a number of structures are present characteristic of second- to fourth-order elements in the glaciotectonic architecture. The other first-order surface is the topographic top of the glaciotectonic complex, which eventually may be replaced by a truncating unconformity.

  18. Real and complex analysis

    CERN Document Server

    Apelian, Christopher; Taft, Earl; Nashed, Zuhair

    2009-01-01

    The Spaces R, Rk, and CThe Real Numbers RThe Real Spaces RkThe Complex Numbers CPoint-Set Topology Bounded SetsClassification of Points Open and Closed SetsNested Intervals and the Bolzano-Weierstrass Theorem Compactness and Connectedness Limits and Convergence Definitions and First Properties Convergence Results for SequencesTopological Results for Sequences Properties of Infinite SeriesManipulations of Series in RFunctions: Definitions and Limits DefinitionsFunctions as MappingsSome Elementary Complex FunctionsLimits of FunctionsFunctions: Continuity and Convergence Continuity Uniform Continuity Sequences and Series of FunctionsThe DerivativeThe Derivative for f: D1 → RThe Derivative for f: Dk → RThe Derivative for f: Dk → RpThe Derivative for f: D → CThe Inverse and Implicit Function TheoremsReal IntegrationThe Integral of f: [a, b] → RProperties of the Riemann Integral Further Development of Integration TheoryVector-Valued and Line IntegralsComplex IntegrationIntroduction to Complex Integrals Fu...

  19. Aquaporins in complex tissues

    DEFF Research Database (Denmark)

    Hamann, S; Zeuthen, T; La Cour, M

    1998-01-01

    Multiple physiological fluid movements are involved in vision. Here we define the cellular and subcellular sites of aquaporin (AQP) water transport proteins in human and rat eyes by immunoblotting, high-resolution immunocytochemistry, and immunoelectron microscopy. AQP3 is abundant in bulbar......, predicting specific roles for each in the complex network through which water movements occur in the eye....

  20. Optical Complex Systems 2008

    Science.gov (United States)

    Brun, Guillaume

    The Optical Complex Systems are more and more in the heart of various systems that industrial applications bring to everyday life. From environment up to spatial applications, OCS is also relevant in monitoring, transportation, robotics, life sciences, sub-marine, and even for agricultural purposes.

  1. Life Complexity and Diversity

    Indian Academy of Sciences (India)

    like sponges or mushrooms have just a few kinds of cells, more complex organisms like crabs or frogs have tens of different kinds of cells. These cells relate to each other in many different ways; the most advanced of these is through connections of nerve cells. Each nerve cell has many processes which link to other nerve, ...

  2. Accessibility in complex networks

    Science.gov (United States)

    Travençolo, B. A. N.; da F. Costa, L.

    2008-12-01

    This Letter describes a method for the quantification of the diversity of non-linear dynamics in complex networks as a consequence of self-avoiding random walks. The methodology is analyzed in the context of theoretical models and illustrated with respect to the characterization of the accessibility in urban streets.

  3. Managing complex child law

    DEFF Research Database (Denmark)

    Svendsen, Idamarie Leth

    2017-01-01

    The article reports the findings of a qualitative study of Danish legal regulation of the public initial assessment of children and young persons and municipal practitioners’ decision-making under this regulation. The regulation mirrors new and complex relations between families and society and t...

  4. The hamstring muscle complex

    NARCIS (Netherlands)

    van der Made, A. D.; Wieldraaijer, T.; Kerkhoffs, G. M.; Kleipool, R. P.; Engebretsen, L.; van Dijk, C. N.; Golanó, P.

    2015-01-01

    The anatomical appearance of the hamstring muscle complex was studied to provide hypotheses for the hamstring injury pattern and to provide reference values of origin dimensions, muscle length, tendon length, musculotendinous junction (MTJ) length as well as width and length of a tendinous

  5. Complexity measures of music

    Science.gov (United States)

    Pease, April; Mahmoodi, Korosh; West, Bruce J.

    2018-03-01

    We present a technique to search for the presence of crucial events in music, based on the analysis of the music volume. Earlier work on this issue was based on the assumption that crucial events correspond to the change of music notes, with the interesting result that the complexity index of the crucial events is mu ~ 2, which is the same inverse power-law index of the dynamics of the brain. The search technique analyzes music volume and confirms the results of the earlier work, thereby contributing to the explanation as to why the brain is sensitive to music, through the phenomenon of complexity matching. Complexity matching has recently been interpreted as the transfer of multifractality from one complex network to another. For this reason we also examine the mulifractality of music, with the observation that the multifractal spectrum of a computer performance is significantly narrower than the multifractal spectrum of a human performance of the same musical score. We conjecture that although crucial events are demonstrably important for information transmission, they alone are not suficient to define musicality, which is more adequately measured by the multifractality spectrum.

  6. A Complex Lens for a Complex Eye.

    Science.gov (United States)

    Stahl, Aaron L; Baucom, Regina S; Cook, Tiffany A; Buschbeck, Elke K

    2017-09-02

    A key innovation for high resolution eyes is a sophisticated lens that precisely focuses light onto photoreceptors. The eyes of holometabolous larvae range from very simple eyes that merely detect light to eyes that are capable of high spatial resolution. Particularly interesting are the bifocal lenses of Thermonectus marmoratus larvae, which differentially focus light on spectrally-distinct retinas. While functional aspects of insect lenses have been relatively well studied, little work has explored their molecular makeup, especially in regard to more complex eye types. To investigate this question, we took a transcriptomic and proteomic approach to identify the major proteins contributing to the principal bifocal lenses of T. marmoratus larvae. Mass spectrometry revealed 10 major lens proteins. Six of these share sequence homology with cuticular proteins, a large class of proteins that are also major components of corneal lenses from adult compound eyes of Drosophila melanogaster and Anopheles gambiae. Two proteins were identified as house-keeping genes and the final two lack any sequence homologies to known genes. Overall the composition seems to follow a pattern of co-opting transparent and optically dense proteins, similar to what has been described for other animal lenses. To identify cells responsible for the secretion of specific lens proteins, we performed in situ hybridization studies and found some expression differences between distal and proximal corneagenous cells. Since the distal cells likely give rise to the periphery and the proximal cells to the center of the lens, our findings highlight a possible mechanism for establishing structural differences that are in line with the bifocal nature of these lenses. A better understanding of lens composition provides insights into the evolution of proper focusing, which is an important step in the transition between low-resolution and high-resolution eyes. © The Author 2017. Published by Oxford University

  7. KAMPOR MEMORIAL COMPLEX

    Directory of Open Access Journals (Sweden)

    Tomaž Krušec

    2013-12-01

    Full Text Available The Kampor Memorial Complex, which was built in 1953 to a design by architect Edvard Ravnikar, is situated on the site of a former cemetery, where between 1942 and 1943 the Italians buried the prisoners who died in the concentration camp on the Island of Rab. Along with the description of the architectural design of the Kampor Memorial Complex on the Island of Rab, the purpose of the paper is to show the most significant models and motivations influencing this particular architectural creation by Ravnikar. The analysis of spatial sequences of the memorial complex served as a basis to study the architectural concept of the cemetery, as described in the paper. The layout of the cemetery is longitudinal. The transversal terraces formulating the lines of graves are longitudinally cut in the middle by a paved path representing the central communication axis of the memorial complex. The path is additionally defined by a sequence of three stone obelisks of different heights, situated along the path. Along the path, three major programmatic emphases can be identified: the entrance vestibule, the platform with the great obelisk and a water tank, and the area below the vaulted structure in stone, also called the Museum. The paper describes the models and influences underlying the creation of Ravnikar's architectural design of the Kampor Memorial Complex on the Island of Rab, particularly Le Corbusier's influence on Ravnikar in the 1940's and the 1950's. In many ways, Ravnikar's stay in Paris and work with Le Corbusier in 1938 round off his basic architectural education; nevertheless, he remained rooted in the classical architectural elements that he obtained in his studies, particularly in the seminar by Jože Plečnik.

  8. Catalytic organometallic anticancer complexes

    Science.gov (United States)

    Dougan, Sarah J.; Habtemariam, Abraha; McHale, Sarah E.; Parsons, Simon; Sadler, Peter J.

    2008-01-01

    Organometallic complexes offer chemistry that is not accessible to purely organic molecules and, hence, potentially new mechanisms of drug action. We show here that the presence of both an iodido ligand and a σ-donor/π-acceptor phenylazopyridine ligand confers remarkable inertness toward ligand substitution on the half-sandwich “piano-stool” ruthenium arene complexes [(η6-arene)Ru(azpy)I]+ (where arene = p-cymene or biphenyl, and azpy = N,N-dimethylphenyl- or hydroxyphenyl-azopyridine) in aqueous solution. Surprisingly, despite this inertness, these complexes are highly cytotoxic to human ovarian A2780 and human lung A549 cancer cells. Fluorescence-trapping experiments in A549 cells suggest that the cytotoxicity arises from an increase in reactive oxygen species. Redox activity of these azopyridine RuII complexes was confirmed by electrochemical measurements. The first one-electron reduction step (half-wave potential −0.2 to −0.4 V) is assignable to reduction of the azo group of the ligand. In contrast, the unbound azopyridine ligands are not readily reduced. Intriguingly the ruthenium complex acted as a catalyst in reactions with the tripeptide glutathione (γ-l-Glu-l-Cys-Gly), a strong reducing agent present in cells at millimolar concentrations; millimolar amounts of glutathione were oxidized to glutathione disulfide in the presence of micromolar ruthenium concentrations. A redox cycle involving glutathione attack on the azo bond of coordinated azopyridine is proposed. Such ligand-based redox reactions provide new concepts for the design of catalytic drugs. PMID:18687892

  9. Interdisciplinary Symposium on Complex Systems

    CERN Document Server

    Rössler, Otto; Zelinka, Ivan

    2015-01-01

    The book you hold in your hands is the outcome of the “2014 Interdisciplinary Symposium on Complex Systems” held in the historical city of Florence. The book consists of 37 chapters from 4 areas of Physical Modeling of Complex Systems, Evolutionary Computations, Complex Biological Systems and Complex Networks. All 4 parts contain contributions that give interesting point of view on complexity in different areas in science and technology. The book starts with a comprehensive overview and classification of complexity problems entitled Physics in the world of ideas: Complexity as Energy”  , followed by chapters about complexity measures and physical principles, its observation, modeling and its applications, to solving various problems including real-life applications. Further chapters contain recent research about evolution, randomness and complexity, as well as complexity in biological systems and complex networks. All selected papers represent innovative ideas, philosophical overviews and state-of-the-...

  10. Complex Feeding Decisions

    Directory of Open Access Journals (Sweden)

    Anna Miles PhD

    2016-08-01

    Full Text Available Objective: Where swallowing difficulties are chronic or progressive, or a patient is palliative, tube feeding is often not deemed appropriate. Instead, patients continue to eat and drink despite the risks of pneumonia and death. There is currently little evidence to guide clinical practice in this field often termed “risk feeding.” This qualitative study investigated staff, patient, and family member perceptions of risk feeding practices in one New Zealand hospital. Method: Twenty-nine staff members and six patients and/or their family were interviewed. Results: Thematic analysis revealed four global themes: supporting practice, communication, complexity of feeding decisions, and patient and family-centered care. Staff described limited education and organizational policy around risk feeding decisions. Communication was considered a major factor in the success. Conclusion: Feeding decisions are complex in the hospital environment. The themes identified in this study provide a foundation for hospital guideline development and implementation.

  11. Reducing GWAS Complexity.

    Science.gov (United States)

    Hazelett, Dennis J; Conti, David V; Han, Ying; Al Olama, Ali Amin; Easton, Doug; Eeles, Rosalind A; Kote-Jarai, Zsofia; Haiman, Christopher A; Coetzee, Gerhard A

    2016-01-01

    Genome-wide association studies (GWAS) have revealed numerous genomic 'hits' associated with complex phenotypes. In most cases these hits, along with surrogate genetic variation as measure by numerous single nucleotide polymorphisms (SNPs) that are in linkage disequilibrium, are not in coding genes making assignment of functionality or causality intractable. Here we propose that fine-mapping along with the matching of risk SNPs at chromatin biofeatures lessen this complexity by reducing the number of candidate functional/causal SNPs. For example, we show here that only on average 2 SNPs per prostate cancer risk locus are likely candidates for functionality/causality; we further propose that this manageable number should be taken forward in mechanistic studies. The candidate SNPs can be looked up for each prostate cancer risk region in 2 recent publications in 2015 (1,2) from our groups.

  12. Complex conductivity of soils

    DEFF Research Database (Denmark)

    Revil, A.; Coperey, A.; Shao, Z.

    2017-01-01

    to 45 kHz. The soil samples are saturated with 6 different NaCl brines with conductivities (0.031, 0.53, 1.15, 5.7, 14.7, and 22 S m-1, NaCl, 25°C) in order to determine their intrinsic formation factor and surface conductivity. This dataset is used to test the predictions of the dynamic Stern......The complex conductivity of soil remains poorly known despite the growing importance of this method in hyrogeophysics. In order to fill this gap of knowledge, we investigate the complex conductivity of 71 soils samples (including 4 peat samples) and one clean sand in the frequency range 0.1 Hertz...

  13. Polystochastic Models for Complexity

    CERN Document Server

    Iordache, Octavian

    2010-01-01

    This book is devoted to complexity understanding and management, considered as the main source of efficiency and prosperity for the next decades. Divided into six chapters, the book begins with a presentation of basic concepts as complexity, emergence and closure. The second chapter looks to methods and introduces polystochastic models, the wave equation, possibilities and entropy. The third chapter focusing on physical and chemical systems analyzes flow-sheet synthesis, cyclic operations of separation, drug delivery systems and entropy production. Biomimetic systems represent the main objective of the fourth chapter. Case studies refer to bio-inspired calculation methods, to the role of artificial genetic codes, neural networks and neural codes for evolutionary calculus and for evolvable circuits as biomimetic devices. The fifth chapter, taking its inspiration from systems sciences and cognitive sciences looks to engineering design, case base reasoning methods, failure analysis, and multi-agent manufacturing...

  14. Gold Thione Complexes

    Directory of Open Access Journals (Sweden)

    Francesco Caddeo

    2014-08-01

    Full Text Available The reaction of the ligand Et4todit (4,5,6,7-Tetrathiocino-[1,2-b:3,4-b']-diimidazolyl-1,3,8,10-tetraethyl-2,9-dithione with gold complexes leads to the dinuclear gold(I complexes [{Au(C6F5}2(Et4todit] and [Au(Et4todit]2(OTf2, which do not contain any gold-gold interactions, or to the gold(III derivative [{Au(C6F53}2(Et4todit]. The crystal structures have been established by X-ray diffraction studies and show that the gold centers coordinate to the sulfur atoms of the imidazoline-2-thione groups.

  15. Complexes Tickling the $ubject

    Directory of Open Access Journals (Sweden)

    Matthew Gildersleeve

    2016-11-01

    Full Text Available This article continues my earlier work of reading Jung with Lacan. This article will develop Zizek’s work on Lacan’s concept of objet petit a by relating it to a phenomenological interpretation of Jung. I use a number of different examples, including Zizek’s interpretation of Francis Bacon, Edvard Munch, Hans Holbein and Johann Gottlieb Fichte, to describe the objet petit a and its relationship to a phenomenological interpretation of complexes. By integrating other Lacanian concepts, such as subject, drive, fantasy, jouissance, gaze, desire, and ego as well as the imaginary, symbolic and Real, this work also highlights how Hegel and Heidegger can elucidate the relationship between objet petit a and complexes. Jung’s transcendent function and the Rosarium Philosophorum also elucidate the relationship between Jung and Lacan.

  16. Complex Strategic Choices

    DEFF Research Database (Denmark)

    Leleur, Steen

    resulting in new material stemming from and focusing on practical application of a systemic approach. The outcome is a coherent and flexible approach named systemic planning. The inclusion of both the theoretical and practical aspects of systemic planning makes this book a key resource for researchers......Effective decision making requires a clear methodology, particularly in a complex world of globalisation. Institutions and companies in all disciplines and sectors are faced with increasingly multi-faceted areas of uncertainty which cannot always be effectively handled by traditional strategies....... Complex Strategic Choices provides clear principles and methods which can guide and support strategic decision making to face the many current challenges. By considering ways in which planning practices can be renewed and exploring the possibilities for acquiring awareness and tools to add value...

  17. Resilience and Complexity

    DEFF Research Database (Denmark)

    Dahlberg, Rasmus

    2015-01-01

    This paper explores two key concepts: resilience and complexity. The first is understood as an emergent property of the latter, and their inter-relatedness is discussed using a three tier approach. First, by exploring the discourse of each concept, next, by analyzing underlying relationships and......, finally, by presenting the Cynefin Framework for Sense-Making as a tool of explicatory potential that has already shown its usefulness in several contexts. I further emphasize linking the two concepts into a common and, hopefully, useful concept. Furthermore, I argue that a resilient system is not merely...... robust. Robustness is a property of simple or complicated systems characterized by predictable behavior, enabling the system to bounce back to its normal state following a perturbation. Resilience, however, is an emergent property of complex adaptive systems. It is suggested that this distinction...

  18. Minimum Complexity Pursuit

    CERN Document Server

    Jalali, Shirin

    2011-01-01

    The fast growing field of compressed sensing is founded on the fact that if a signal is 'simple' and has some 'structure', then it can be reconstructed accurately with far fewer samples than its ambient dimension. Many different plausible structures have been explored in this field, ranging from sparsity to low-rankness and to finite rate of innovation. However, there are important abstract questions that are yet to be answered. For instance, what are the general abstract meanings of 'structure' and 'simplicity'? Do there exist universal algorithms for recovering such simple structured objects from fewer samples than their ambient dimension? In this paper, we aim to address these two questions. Using algorithmic information theory tools such as Kolmogorov complexity, we provide a unified method of describing 'simplicity' and 'structure'. We then explore the performance of an algorithm motivated by Ocam's Razor (called MCP for minimum complexity pursuit) and show that it requires $O(k\\log n)$ number of samples...

  19. Complex Polynomial Vector Fields

    DEFF Research Database (Denmark)

    Dias, Kealey

    The two branches of dynamical systems, continuous and discrete, correspond to the study of differential equations (vector fields) and iteration of mappings respectively. In holomorphic dynamics, the systems studied are restricted to those described by holomorphic (complex analytic) functions...... or meromorphic (allowing poles as singularities) functions. There already exists a well-developed theory for iterative holomorphic dynamical systems, and successful relations found between iteration theory and flows of vector fields have been one of the main motivations for the recent interest in holomorphic...... vector fields. Since the class of complex polynomial vector fields in the plane is natural to consider, it is remarkable that its study has only begun very recently. There are numerous fundamental questions that are still open, both in the general classification of these vector fields, the decomposition...

  20. Complexity of the Ephemeral

    DEFF Research Database (Denmark)

    Ekman, Ulrik

    2015-01-01

    This brief article presents the everyday cultural use of the Snapchat instant messaging application for video chats as an exemplary case of the challenges confronting studies of cinematics in an epoch marked by the rise in network societies of ubiquitous mobile and social media and technics....... It proffers and begins to detail the argument that snap video chats cannot be denigrated as mere ‘shorts’ but must be approached as spatiotemporally and experientally complex....

  1. Operational Shock Complexity Theory

    Science.gov (United States)

    2005-05-26

    too kind to state that they envisaged complexity theory. The idea of Cognitive Dissonance is accredited to Leon Festinger and is at heart that awful...on psychological elements. 3 This monograph will only touch on a couple of the areas of change and why the concept of operational shock must evolve...attack (and thus was physical in nature), which would lead to a psychological outcome, namely the loss of will to continue fighting.44 This will to

  2. Complex regional pain syndrome

    OpenAIRE

    V. A. Koryachkin

    2011-01-01

    Complex regional pain syndrome (CRPS) previously known as reflex sympathetic dystrophy is a chronic neurological disorder involving the limbs characterized by disabling pain, swelling, vasomotor instability, sudomotor abnormality, and impairment of motor function. CRPS is not uncommon after hand surgery and may complicate post-operative care. There is no specific diagnostic test for CRPS and the diagnosis is based on history, clinical examination, and supportive laboratory findings. Recent mo...

  3. Arithmetic of Complex Manifolds

    CERN Document Server

    Lange, Herbert

    1989-01-01

    It was the aim of the Erlangen meeting in May 1988 to bring together number theoretists and algebraic geometers to discuss problems of common interest, such as moduli problems, complex tori, integral points, rationality questions, automorphic forms. In recent years such problems, which are simultaneously of arithmetic and geometric interest, have become increasingly important. This proceedings volume contains 12 original research papers. Its main topics are theta functions, modular forms, abelian varieties and algebraic three-folds.

  4. Complex Flows by Nanohydrodynamics

    Energy Technology Data Exchange (ETDEWEB)

    Alley, E; Covello, P; Alder, B

    2004-03-01

    The study of complex flows by particle simulations is speeded up over molecular dynamics (MD) by more than two orders of magnitude by employing a stochastic collision dynamics method (DSMC) extended to high density (CBA). As a consequence, a picture generated on a single processor shows the typical features of the Rayleigh-Taylor instability and is in quantitative agreement with the experimentally found long time behavior.

  5. Control of complex systems

    CERN Document Server

    Albertos, Pedro; Blanke, Mogens; Isidori, Alberto; Schaufelberger, Walter; Sanz, Ricardo

    2001-01-01

    The world of artificial systems is reaching complexity levels that es­ cape human understanding. Surface traffic, electricity distribution, air­ planes, mobile communications, etc. , are examples that demonstrate that we are running into problems that are beyond classical scientific or engi­ neering knowledge. There is an ongoing world-wide effort to understand these systems and develop models that can capture its behavior. The reason for this work is clear, if our lack of understanding deepens, we will lose our capability to control these systems and make they behave as we want. Researchers from many different fields are trying to understand and develop theories for complex man-made systems. This book presents re­ search from the perspective of control and systems theory. The book has grown out of activities in the research program Control of Complex Systems (COSY). The program has been sponsored by the Eu­ ropean Science Foundation (ESF) which for 25 years has been one of the leading players in stimula...

  6. Advanced complex trait analysis.

    Science.gov (United States)

    Gray, A; Stewart, I; Tenesa, A

    2012-12-01

    The Genome-wide Complex Trait Analysis (GCTA) software package can quantify the contribution of genetic variation to phenotypic variation for complex traits. However, as those datasets of interest continue to increase in size, GCTA becomes increasingly computationally prohibitive. We present an adapted version, Advanced Complex Trait Analysis (ACTA), demonstrating dramatically improved performance. We restructure the genetic relationship matrix (GRM) estimation phase of the code and introduce the highly optimized parallel Basic Linear Algebra Subprograms (BLAS) library combined with manual parallelization and optimization. We introduce the Linear Algebra PACKage (LAPACK) library into the restricted maximum likelihood (REML) analysis stage. For a test case with 8999 individuals and 279,435 single nucleotide polymorphisms (SNPs), we reduce the total runtime, using a compute node with two multi-core Intel Nehalem CPUs, from ∼17 h to ∼11 min. The source code is fully available under the GNU Public License, along with Linux binaries. For more information see http://www.epcc.ed.ac.uk/software-products/acta. a.gray@ed.ac.uk Supplementary data are available at Bioinformatics online.

  7. The Emparassment of Complexity

    Science.gov (United States)

    Nowotny, Helga

    My vision of complexity sciences targets their potential to extend the range, precision, and depth in making predictions. While this has always been the ambition and yardstick for the physicalmathematical sciences, complexity sciences now allow to include society and social behavior - to some extent. There is agreement that society is a complex adaptive system, CAS, with a few peculiarities. Ignoring, downplaying, or naturalizing them, i.e. to take them as essential and given, carries the risk to end up with abstractions which are cutoff from the dynamics of societal contexts. One of the peculiarities of society as a CAS is that the models with which we try to make sense of the world are invented and constructed by us. It is humans who make observations and provide the assumptions on which models are based. Humans leave traces that are collected and processed to be transformed into data. Humans decide to which purpose they will be put and how they will be repurposed. Humans are object of research and subject. Coping with these peculiarities requires an inbuilt reflexivity. Practioners must perform a double act and do so repeatedly. They must engage in a focused way with their scientific work and equally distance themselves by critically reflecting their often tacit assumptions. A friend of mine, Yehuda Elkana, called this twotier thinking...

  8. Predictive Surface Complexation Modeling

    Energy Technology Data Exchange (ETDEWEB)

    Sverjensky, Dimitri A. [Johns Hopkins Univ., Baltimore, MD (United States). Dept. of Earth and Planetary Sciences

    2016-11-29

    Surface complexation plays an important role in the equilibria and kinetics of processes controlling the compositions of soilwaters and groundwaters, the fate of contaminants in groundwaters, and the subsurface storage of CO2 and nuclear waste. Over the last several decades, many dozens of individual experimental studies have addressed aspects of surface complexation that have contributed to an increased understanding of its role in natural systems. However, there has been no previous attempt to develop a model of surface complexation that can be used to link all the experimental studies in order to place them on a predictive basis. Overall, my research has successfully integrated the results of the work of many experimentalists published over several decades. For the first time in studies of the geochemistry of the mineral-water interface, a practical predictive capability for modeling has become available. The predictive correlations developed in my research now enable extrapolations of experimental studies to provide estimates of surface chemistry for systems not yet studied experimentally and for natural and anthropogenically perturbed systems.

  9. [Complex posttraumatic stress disorder].

    Science.gov (United States)

    Green, Tamar; Kotler, Moshe

    2007-11-01

    The characteristic symptoms resulting from exposure to an extreme trauma include three clusters of symptoms: persistent experience of the traumatic event, persistent avoidance of stimuli associated with the trauma and persistent symptoms of increased arousal. Beyond the accepted clusters of symptoms for posttraumatic stress disorder exists a formation of symptoms related to exposure to extreme or prolonged stress e.g. childhood abuse, physical violence, rape, and confinement within a concentration camp. With accumulated evidence of the existence of these symptoms began a trail to classify a more complex syndrome, which included, but was not confined to the symptoms of posttraumatic stress disorder. This review addresses several subjects for study in complex posttraumatic stress disorder, which is a complicated and controversial topic. Firstly, the concept of complex posttraumatic stress disorder is presented. Secondly, the professional literature relevant to this disturbance is reviewed and finally, the authors present the polemic being conducted between the researchers of posttraumatic disturbances regarding validity, reliability and the need for separate diagnosis for these symptoms.

  10. Emergent complex network geometry.

    Science.gov (United States)

    Wu, Zhihao; Menichetti, Giulia; Rahmede, Christoph; Bianconi, Ginestra

    2015-05-18

    Networks are mathematical structures that are universally used to describe a large variety of complex systems such as the brain or the Internet. Characterizing the geometrical properties of these networks has become increasingly relevant for routing problems, inference and data mining. In real growing networks, topological, structural and geometrical properties emerge spontaneously from their dynamical rules. Nevertheless we still miss a model in which networks develop an emergent complex geometry. Here we show that a single two parameter network model, the growing geometrical network, can generate complex network geometries with non-trivial distribution of curvatures, combining exponential growth and small-world properties with finite spectral dimensionality. In one limit, the non-equilibrium dynamical rules of these networks can generate scale-free networks with clustering and communities, in another limit planar random geometries with non-trivial modularity. Finally we find that these properties of the geometrical growing networks are present in a large set of real networks describing biological, social and technological systems.

  11. Complexity Leadership: A Theoretical Perspective

    Science.gov (United States)

    Baltaci, Ali; Balci, Ali

    2017-01-01

    Complex systems are social networks composed of interactive employees interconnected through collaborative, dynamic ties such as shared goals, perspectives and needs. Complex systems are largely based on "the complex system theory". The complex system theory focuses mainly on finding out and developing strategies and behaviours that…

  12. Copper complexes as chemical nucleases

    Indian Academy of Sciences (India)

    Keywords. Copper(II) complexes; nuclease activity; catalytic properties; DNA binding. Abstract. Redox active mononuclear and binuclear copper(II) complexes have been prepared and structurally characterized. ... The cleavage activity of the bis-dpq complex is significantly higher than the bis-phen complex of copper(II).

  13. Transition Complexity of Incomplete DFAs

    Directory of Open Access Journals (Sweden)

    Yuan Gao

    2010-08-01

    Full Text Available In this paper, we consider the transition complexity of regular languages based on the incomplete deterministic finite automata. A number of results on Boolean operations have been obtained. It is shown that the transition complexity results for union and complementation are very different from the state complexity results for the same operations. However, for intersection, the transition complexity result is similar to that of state complexity.

  14. The Stigma Complex

    Science.gov (United States)

    Pescosolido, Bernice A.; Martin, Jack K.

    2016-01-01

    Since the beginning of the twenty-first century, research on stigma has continued. Building on conceptual and empirical work, the recent period clarifies new types of stigmas, expansion of measures, identification of new directions, and increasingly complex levels. Standard beliefs have been challenged, the relationship between stigma research and public debates reconsidered, and new scientific foundations for policy and programs suggested. We begin with a summary of the most recent Annual Review articles on stigma, which reminded sociologists of conceptual tools, informed them of developments from academic neighbors, and claimed findings from the early period of “resurgence.” Continued (even accelerated) progress has also revealed a central problem. Terms and measures are often used interchangeably, leading to confusion and decreasing accumulated knowledge. Drawing from this work but focusing on the past 14 years of stigma research (including mental illness, sexual orientation, HIV/AIDS, and race/ethnicity), we provide a theoretical architecture of concepts (e.g., prejudice, experienced/received discrimination), drawn together through a stigma process (i.e., stigmatization), based on four theoretical premises. Many characteristics of the mark (e.g., discredited, concealable) and variants (i.e., stigma types and targets) become the focus of increasingly specific and multidimensional definitions. Drawing from complex and systems science, we propose a stigma complex, a system of interrelated, heterogeneous parts bringing together insights across disciplines to provide a more realistic and complicated sense of the challenge facing research and change efforts. The Framework Integrating Normative Influences on Stigma (FINIS) offers a multilevel approach that can be tailored to stigmatized statuses. Finally, we outline challenges for the next phase of stigma research, with the goal of continuing scientific activity that enhances our understanding of stigma and builds

  15. Complex Auditory Signals

    Science.gov (United States)

    1988-09-01

    I I!ED REPORT DOCUMENTATION PAGE AD-A 199 332 b RESTRICTIVE MARKINGS 3. DISTRIBUTION/ AVAILABILITY OF REPORT A.Proved for pj ." ic release 2b...remarkably little experimental nent complexes. In the first experiment, a single evidence documenting these claims. Viemeister component of a 21-component...deci relts~to a l’rn NI betwen CtMRd tipoe ( 1959 ) and Gabriel and Colburn ( 1981 ) xk Ill be con- ot:ilcl tlope dlcelati ’o nos dids e lceredl .t% h

  16. Computability, complexity, logic

    CERN Document Server

    Börger, Egon

    1989-01-01

    The theme of this book is formed by a pair of concepts: the concept of formal language as carrier of the precise expression of meaning, facts and problems, and the concept of algorithm or calculus, i.e. a formally operating procedure for the solution of precisely described questions and problems. The book is a unified introduction to the modern theory of these concepts, to the way in which they developed first in mathematical logic and computability theory and later in automata theory, and to the theory of formal languages and complexity theory. Apart from considering the fundamental themes an

  17. Complex regional pain syndrome

    Directory of Open Access Journals (Sweden)

    Sandeep J Sebastin

    2011-01-01

    Full Text Available Complex regional pain syndrome (CRPS previously known as reflex sympathetic dystrophy is a chronic neurological disorder involving the limbs characterized by disabling pain, swelling, vasomotor instability, sudomotor abnormality, and impairment of motor function. CRPS is not uncommon after hand surgery and may complicate post-operative care. There is no specific diagnostic test for CRPS and the diagnosis is based on history, clinical examination, and supportive laboratory findings. Recent modifications to diagnostic criteria have enabled clinicians to diagnose this disease more consistently. This review gives a synopsis of CRPS and discusses the diagnosis, pathophysiology, and treatment options based on the limited evidence in the literature.

  18. Complex Strategic Choices

    DEFF Research Database (Denmark)

    Leleur, Steen

    resulting in new material stemming from and focusing on practical application of a systemic approach. The outcome is a coherent and flexible approach named systemic planning. The inclusion of both the theoretical and practical aspects of systemic planning makes this book a key resource for researchers......Effective decision making requires a clear methodology, particularly in a complex world of globalisation. Institutions and companies in all disciplines and sectors are faced with increasingly multi-faceted areas of uncertainty which cannot always be effectively handled by traditional strategies...

  19. Fluorido complexes of technetium

    Energy Technology Data Exchange (ETDEWEB)

    Mariappan Balasekaran, Samundeeswari

    2013-07-04

    Fluorine chemistry has received considerable interest during recent years due to its significant role in the life sciences, especially for drug development. Despite the great nuclear medicinal importance of the radioactive metal technetium in radiopharmaceuticals, its coordination chemistry with the fluorido ligand is by far less explored than that of other ligands. Up to now, only a few technetium fluorides are known. This thesis contains the synthesis, spectroscopic and structural characterization of novel technetium fluorides in the oxidation states ''+1'', ''+2'', ''+4'' and ''+6''. In the oxidation state ''+6'', the fluoridotechnetates were synthesized either from nitridotechnetic(VI) acid or from pertechnetate by using reducing agent and have been isolated as cesium or tetraethylammonium salts. The compounds were characterized spectroscopically and structurally. In the intermediate oxidation state ''+4'', hexafluoridotechnetate(IV) was known for long time and studied spectroscopically. This thesis reports novel and improved syntheses and solved the critical issues of early publications such as the color, some spectroscopic properties and the structure of this key compound. Single crystal analyses of alkali metal, ammonium and tetramethylammonium salts of hexafluoridotechnetate(IV) are presented. In aqueous alkaline solutions, the ammonium salt of hexafluoridotechnetate(IV) undergoes hydrolysis and forms an oxido-bridged dimeric complex. It is the first step hydrolysis product of hexafluoridotechnetate(IV) and was characterized by spectroscopic and crystallographic methods. Low-valent technetium fluorides with the metal in the oxidation states of ''+2'' or ''+1'' are almost unknown. A detailed description of the synthesis and characterization of pentafluoridonitrosyltechnetate(II) is presented. The

  20. Complex adaptive systems ecology

    DEFF Research Database (Denmark)

    Sommerlund, Julie

    2003-01-01

    In the following, I will analyze two articles called Complex Adaptive Systems EcologyI & II (Molin & Molin, 1997 & 2000). The CASE-articles are some of the more quirkyarticles that have come out of the Molecular Microbial Ecology Group - a groupwhere I am currently making observational studies....... They are the result of acooperation between Søren Molin, professor in the group, and his brother, JanMolin, professor at Department of Organization and Industrial Sociology atCopenhagen Business School. The cooperation arises from the recognition that bothmicrobial ecology and sociology/organization theory works...

  1. Kinetics of complex plasmas

    CERN Document Server

    Sodha, Mahendra Singh

    2014-01-01

    The presentation in the book is based on charge balance on the dust particles, number and energy balance of the constituents and atom-ion-electron interaction in the gaseous plasma. Size distribution of dust particles, statistical mechanics, Quantum effects in electron emission from and accretion on dust particles and nonlinear interaction of complex plasmas with electric and electromagnetic fields have been discussed in the book. The book introduces the reader to basic concepts and typical applications. The book should be of use to researchers, engineers and graduate students.

  2. Exploring complex networks.

    Science.gov (United States)

    Strogatz, S H

    2001-03-08

    The study of networks pervades all of science, from neurobiology to statistical physics. The most basic issues are structural: how does one characterize the wiring diagram of a food web or the Internet or the metabolic network of the bacterium Escherichia coli? Are there any unifying principles underlying their topology? From the perspective of nonlinear dynamics, we would also like to understand how an enormous network of interacting dynamical systems-be they neurons, power stations or lasers-will behave collectively, given their individual dynamics and coupling architecture. Researchers are only now beginning to unravel the structure and dynamics of complex networks.

  3. Genetics of complex diseases

    DEFF Research Database (Denmark)

    Mellerup, Erling; Møller, Gert Lykke; Koefoed, Pernille

    2012-01-01

    A complex disease with an inheritable component is polygenic, meaning that several different changes in DNA are the genetic basis for the disease. Such a disease may also be genetically heterogeneous, meaning that independent changes in DNA, i.e. various genotypes, can be the genetic basis...... for the disease. Each of these genotypes may be characterized by specific combinations of key genetic changes. It is suggested that even if all key changes are found in genes related to the biology of a certain disease, the number of combinations may be so large that the number of different genotypes may be close...

  4. Macroevolution of complex retroviruses.

    Science.gov (United States)

    Katzourakis, Aris; Gifford, Robert J; Tristem, Michael; Gilbert, M Thomas P; Pybus, Oliver G

    2009-09-18

    Retroviruses can leave a "fossil record" in their hosts' genomes in the form of endogenous retroviruses. Foamy viruses, complex retroviruses that infect mammals, have been notably absent from this record. We have found an endogenous foamy virus within the genomes of sloths and show that foamy viruses were infecting mammals more than 100 million years ago and codiverged with their hosts across an entire geological era. Our analysis highlights the role of evolutionary constraint in maintaining viral genome structure and indicates that accessory genes and mammalian mechanisms of innate immunity are the products of macroevolutionary conflict played out over a geological time scale.

  5. Complex performance in construction

    DEFF Research Database (Denmark)

    Bougrain, Frédéric; Forman, Marianne; Gottlieb, Stefan Christoffer

    of the industry. The main objective of this project was to understand how the development of integrated solutions in construction led to distinct configuration of actors and structures. Furthermore, the project analyses whether these changes modified project processes and contributed to the delivery of new value...... to the end users. This report summarises the results from work undertaken in the international collaborative project “Procuring and Operating Complex Products and Systems in Construction” (POCOPSC). POCOPSC was carried out in the period 2010-2014. The project was executed in collaboration between CSTB...

  6. Organization of complex networks

    Science.gov (United States)

    Kitsak, Maksim

    Many large complex systems can be successfully analyzed using the language of graphs and networks. Interactions between the objects in a network are treated as links connecting nodes. This approach to understanding the structure of networks is an important step toward understanding the way corresponding complex systems function. Using the tools of statistical physics, we analyze the structure of networks as they are found in complex systems such as the Internet, the World Wide Web, and numerous industrial and social networks. In the first chapter we apply the concept of self-similarity to the study of transport properties in complex networks. Self-similar or fractal networks, unlike non-fractal networks, exhibit similarity on a range of scales. We find that these fractal networks have transport properties that differ from those of non-fractal networks. In non-fractal networks, transport flows primarily through the hubs. In fractal networks, the self-similar structure requires any transport to also flow through nodes that have only a few connections. We also study, in models and in real networks, the crossover from fractal to non-fractal networks that occurs when a small number of random interactions are added by means of scaling techniques. In the second chapter we use k-core techniques to study dynamic processes in networks. The k-core of a network is the network's largest component that, within itself, exhibits all nodes with at least k connections. We use this k-core analysis to estimate the relative leadership positions of firms in the Life Science (LS) and Information and Communication Technology (ICT) sectors of industry. We study the differences in the k-core structure between the LS and the ICT sectors. We find that the lead segment (highest k-core) of the LS sector, unlike that of the ICT sector, is remarkably stable over time: once a particular firm enters the lead segment, it is likely to remain there for many years. In the third chapter we study how

  7. The Orpheus complex.

    Science.gov (United States)

    Dawson, T

    2000-04-01

    This paper examines the possible psychological implications of two adaptations of the myth of Orpheus and Eurydice, both of which were completed in 1997. The first is by a man: 'Deconstructing Harry', a film by Woody Allen. The second is by a woman: 'Eurydice in the Underworld', a short story written by Kathy Acker in the last year of her life. The paper argues that there are only four 'necessary events' in the myth of Orpheus and Eurydice. It defines the sequence of these events as a 'mythic pattern' that represents the experience of loss, unconscious yearning, depression, and psychological inflation. The film is examined as an expression of an 'Orpheus complex', the short story as an expression of an 'Eurydice complex'. The paper suggests a possible reason for the persistence of interest in the myth throughout the twentieth century. Although it notes that women appear to find it easier to free themselves from identification with the mythic pattern, it also provides reasons for thinking that men may be about to do the same.

  8. The authority of complexity.

    Science.gov (United States)

    Stehr, N; Grundmann, R

    2001-06-01

    The assertion about the unique 'complexity' or the peculiarly intricate character of social phenomena has, at least within sociology, a long, venerable and virtually uncontested tradition. At the turn of the last century, classical social theorists, for example, Georg Simmel and Emile Durkheim, made prominent and repeated reference to this attribute of the subject matter of sociology and the degree to which it complicates, even inhibits the develop and application of social scientific knowledge. Our paper explores the origins, the basis and the consequences of this assertion and asks in particular whether the classic complexity assertion still deserves to be invoked in analyses that ask about the production and the utilization of social scientific knowledge in modern society. We present John Maynard Keynes' economic theory and its practical applications as an illustration. We conclude that the practical value of social scientific knowledge is not dependent on a faithful, in the sense of complete, representation of social reality. Instead, social scientific knowledge that wants to optimize its practicality has to attend and attach itself to elements of social situations that can be altered or are actionable.

  9. Bound Exciton Complexes

    Science.gov (United States)

    Meyer, B. K.

    In the preceding chapter, we concentrated on the properties of free excitons. These free excitons may move through the sample and hit a trap, a nonradiative or a radiative recombination center. At low temperatures, the latter case gives rise to either deep center luminescence, mentioned in Sect. 7.1 and discussed in detail in Chap. 9, or to the luminescence of bound exciton complexes (BE or BEC). The chapter continues with the most prominent of these BECs, namely A-excitons bound to neutral donors. The next aspects are the more weakly BEs at ionized donors. The Sect. 7.4 treats the binding or localization energies of BEC from a theoretical point of view, while Sect. 7.5 is dedicated to excited states of BECs, which contain either holes from deeper valence bands or an envelope function with higher quantum numbers. The last section is devoted to donor-acceptor pair transitions. There is no section devoted specifically to excitons bound to neutral acceptors, because this topic is still partly controversially discussed. Instead, information on these A0X complexes is scattered over the whole chapter, however, with some special emphasis seen in Sects. 7.1, 7.4, and 7.5.

  10. Complexity in language acquisition.

    Science.gov (United States)

    Clark, Alexander; Lappin, Shalom

    2013-01-01

    Learning theory has frequently been applied to language acquisition, but discussion has largely focused on information theoretic problems-in particular on the absence of direct negative evidence. Such arguments typically neglect the probabilistic nature of cognition and learning in general. We argue first that these arguments, and analyses based on them, suffer from a major flaw: they systematically conflate the hypothesis class and the learnable concept class. As a result, they do not allow one to draw significant conclusions about the learner. Second, we claim that the real problem for language learning is the computational complexity of constructing a hypothesis from input data. Studying this problem allows for a more direct approach to the object of study--the language acquisition device-rather than the learnable class of languages, which is epiphenomenal and possibly hard to characterize. The learnability results informed by complexity studies are much more insightful. They strongly suggest that target grammars need to be objective, in the sense that the primitive elements of these grammars are based on objectively definable properties of the language itself. These considerations support the view that language acquisition proceeds primarily through data-driven learning of some form. Copyright © 2013 Cognitive Science Society, Inc.

  11. Polyhydride complexes for hydrogen storage

    Energy Technology Data Exchange (ETDEWEB)

    Jensen, C.M. [Univ. of Hawaii, Honolulu, HI (United States)

    1995-09-01

    Polyhydride metal complexes are being developed for application in hydrogen storage. Efforts have focused on developing complexes with improved available hydrogen weight percentages. We have explored the possibility that complexes containing aromatic hydrocarbon ligands could store hydrogen at both the metal center and in the ligands. We have synthesized novel indenyl hydride complexes and explored their reactivity with hydrogen. The reversible hydrogenation of [IrH{sub 3}(PPh{sub 3})({eta}{sup 5}-C{sub 10}H{sub 7})]{sup +} has been achieved. While attempting to prepare {eta}{sup 6}-tetrahydronaphthalene complexes, we discovered that certain polyhydride complexes catalyze both the hydrogenation and dehydrogenation of tetrahydronaphthalene.

  12. Shapes of interacting RNA complexes

    DEFF Research Database (Denmark)

    Fu, Benjamin Mingming; Reidys, Christian

    2014-01-01

    Shapes of interacting RNA complexes are studied using a filtration via their topological genus. A shape of an RNA complex is obtained by (iteratively) collapsing stacks and eliminating hairpin loops.This shape-projection preserves the topological core of the RNA complex and for fixed topological...... genus there are only finitely many such shapes. Our main result is a new bijection that relates the shapes of RNA complexes with shapes of RNA structures. This allows to compute the shape polynomial of RNA complexes via the shape polynomial of RNA structures. We furthermore present a linear time uniform...... sampling algorithm for shapes of RNA complexes of fixed topological genus....

  13. Syntactic Complexity as an Aspect of Text Complexity

    Science.gov (United States)

    Frantz, Roger S.; Starr, Laura E.; Bailey, Alison L.

    2015-01-01

    Students' ability to read complex texts is emphasized in the Common Core State Standards (CCSS) for English Language Arts and Literacy. The standards propose a three-part model for measuring text complexity. Although the model presents a robust means for determining text complexity based on a variety of features inherent to a text as well as…

  14. Complex agent networks: An emerging approach for modeling complex systems

    NARCIS (Netherlands)

    Mei, S.; Zarrabi, N.; Lees, M.; Sloot, P.M.A.

    2015-01-01

    Complexity and complex systems are all around us: from molecular and cellular systems in biology up to economics and human societies. There is an urgent need for methods that can capture the multi-scale spatio-temporal characteristics of complex systems. Recent emphasis has centered on two methods

  15. [COMPLEX REGIONAL PAIN SYNDROME].

    Science.gov (United States)

    Blažeković, Ivan; Bilić, Ervina; Žagar, Marija; Anić, Branimir

    2015-01-01

    Complex regional pain syndrome (CRPS) represents a state of constant and often disabling pain, affecting one region (usually hand) and often occurs after a trauma whose severity does not correlate with the level of pain. The older term for this condition of chronic pain associated with motor and autonomic symptoms is reflex sympathetic dystrophy or causalgia. The aim of this review, based on contemporary literature, is to show the epidemiology and etiology, proposed pathophysiological mechanisms, method of diagnosis and treatment options, prevention and mitigation of this under-recognized disease. CRPS I occurs without known neurological damage, unlike CRPS II, where the history of trauma is present and in some cases damage to the peripheral nervous system can be objectively assessed using electromyoneurography. New diagnostic methods, such as quantitative sensory testing (CST), challenge this division because the CST findings in patients with CRPS I can suggest damage to Adelta peripheral nerve fibers. Except for distinguishing type I and type II disease, it is important to bear in mind the diversity of clinical presentation of CRPS in acute and chronic phase of the disease. This regional pain syndrome typically includes the autonomic and motor signs and thus differs from other peripheral neuropathic pain syndromes. The complexity of the clinical presentation indicates the likely presence of different pathophysiological mechanisms underlying this disease. Previous studies have demonstrated the autonomic dysfunction, neurogenic inflammation and neuroplastic changes. The diagnosis of CRPS is based on anamnesis and clinical examination on the basis of which the disease can be graded according to the Budapest Criteria. A valuable aid in differentiating subtypes of the disease is electromyoneurography. The treatment of CRPS is as complex as the clinical picture and the pathophysiology of the disease and requires interdisciplinary cooperation and individual approach

  16. OF AGROINDUSTRIAL COMPLEX MANAGEMENT

    Directory of Open Access Journals (Sweden)

    Ruslan E. Mansurov

    2017-06-01

    Full Text Available The relevance of this work is determined, on the one hand, by tightening of the foreign political situation and its possible negative impact on the food security of the country, and, on the other hand, by the crisis of the domestic agricultural sector. These factors demand the development of new approaches to regional agroindustrial complex (AIC management. The aim is to develop a methodology for assessing the level of food self-sufficiency in main food areas of the Volgograd region. The author used the results of the statistical materials of AIC of the Volgograd region for 2016. The analytical methods included mathematical analysis and comparison. The main results are as follows. Based on the analysis of the current situation to ensure food security of Russia it was proved that at the present time it is necessary to develop effective indicators showing the level of self-sufficiency in basic food regions. It was also revealed that at the moment this indicator in the system of regional agrarian and industrial complex is not controlled. As a result of generalization of existing approaches the author’s method of rating the level of self-sufficiency of regions was offered. Its testing was carried out in several districts of the Volgograd region. The proposed authoring method of rating estimation of self-sufficiency in basic foodstuffs can be used in the regional agroindustrial complex management system at the federal and local levels. It can be used to rank areas in terms of their self-sufficiency in basic foodstuffs. This allows us to focus on the development of backward areas of agro-food and make appropriate management decisions. The final rating value - 0.759 obtained by the results of analysis of the situation in the Volgograd region means that the situation in matters of selfsufficiency in basic foodstuffs in general is good. However, we should aim at the maximum possible value of the rating - 1. In the application of the proposed

  17. Nuclear Weapons Complex reconfiguration study

    Energy Technology Data Exchange (ETDEWEB)

    1991-01-01

    Shortly after assuming duties as Secretary of Energy, I reviewed the Nuclear Weapons Complex Modernization Report'' submitted to the Congress in January 1989 as required by the National Defense Authorization Act of 1988 and 1989. My review showed that several of the report's assumptions needed to be re-evaluated. During this eighteen-month review, dramatic world changes forced further reassessments of the future Nuclear Weapons Complex. These changes are reflected in the new report. The new report presents a plan to achieve a reconfigured complex, called Complex-21. Complex-21 would be smaller, less diverse, and less expensive to operated than the Complex of today. Complex-21 would be able to safely and reliability support nuclear deterrent stockpile objectives set forth by the President and funded by the Congress. It would be consistent with realities of the emerging international security environment and flexible enough to accommodate the likely range of deterrent contingencies. In addition, Complex-21 would be constructed and operated to comply with all applicable federal, state, and local laws, regulations, and orders. Achieving Complex-21 will require significant resources. This report provides and organized approach toward selecting the most appropriate configuration for Complex-21, satisfying environmental requirements, and minimizing costs. The alternative -- to continue to use piecemeal fixes to run an antiquated complex -- will be more expensive and provide a less reliable Nuclear Weapons Complex. As a consequence, implementation of the Complex-21 plan is considered necessary to ensure continued viability of our nuclear deterrent.

  18. Complex Algebraic Varieties

    CERN Document Server

    Peternell, Thomas; Schneider, Michael; Schreyer, Frank-Olaf

    1992-01-01

    The Bayreuth meeting on "Complex Algebraic Varieties" focussed on the classification of algebraic varieties and topics such as vector bundles, Hodge theory and hermitian differential geometry. Most of the articles in this volume are closely related to talks given at the conference: all are original, fully refereed research articles. CONTENTS: A. Beauville: Annulation du H(1) pour les fibres en droites plats.- M. Beltrametti, A.J. Sommese, J.A. Wisniewski: Results on varieties with many lines and their applications to adjunction theory.- G. Bohnhorst, H. Spindler: The stability of certain vector bundles on P(n) .- F. Catanese, F. Tovena: Vector bundles, linear systems and extensions of (1).- O. Debarre: Vers uns stratification de l'espace des modules des varietes abeliennes principalement polarisees.- J.P. Demailly: Singular hermitian metrics on positive line bundles.- T. Fujita: On adjoint bundles of ample vector bundles.- Y. Kawamata: Moderate degenerations of algebraic surfaces.- U. Persson: Genus two fibra...

  19. Complex algebraic geometry

    CERN Document Server

    Kollár, János

    1997-01-01

    This volume contains the lectures presented at the third Regional Geometry Institute at Park City in 1993. The lectures provide an introduction to the subject, complex algebraic geometry, making the book suitable as a text for second- and third-year graduate students. The book deals with topics in algebraic geometry where one can reach the level of current research while starting with the basics. Topics covered include the theory of surfaces from the viewpoint of recent higher-dimensional developments, providing an excellent introduction to more advanced topics such as the minimal model program. Also included is an introduction to Hodge theory and intersection homology based on the simple topological ideas of Lefschetz and an overview of the recent interactions between algebraic geometry and theoretical physics, which involve mirror symmetry and string theory.

  20. Complexity, Metastability and Nonextensivity

    Science.gov (United States)

    Beck, C.; Benedek, G.; Rapisarda, A.; Tsallis, C.

    Work and heat fluctuations in systems with deterministic and stochastic forces / E. G. D. Cohen and R. Van Zon -- Is the entropy S[symbol] extensive or nonextensive? / C. Tsallis -- Superstatistics: recent developments and applications / C. Beck -- Two stories outside Boltzmann-Gibbs statistics: Mori's Q-phase transitions and glassy dynamics at the onset of chaos / A. Robledo, F. Baldovin and E. Mayoral -- Time-averages and the heat theorem / A. Carati -- Fundamental formulae and numerical evidences for the central limit theorem in Tsallis statistics / H. Suyari -- Generalizing the Planck distribution / A. M. C. Soma and C. Tsallis -- The physical roots of complexity: renewal or modulation? / P. Grigolini -- Nonequivalent ensembles and metastability / H. Touchette and R. S. Ellis -- Statistical physics for cosmic structures / L. Pietronero and F. Sylos Labini -- Metastability and anomalous behavior in the HMF model: connections to nonextensive thermodynamics and glassy dynamics / A. Pluchino, A. Rapisarda and V. Latora -- Vlasov analysis of relaxation and meta-equilibrium / C. Anteneodo and R. O. Vallejos -- Weak chaos in large conservative systems - infinite-range coupled standard maps / L. G. Moyano, A. P. Majtey and C. Tsallis -- Deterministc aging / E. Barkai -- Edge of chaos of the classical kicked top map: sensitivity to initial conditions / S. M. Duarte Queirós and C. Tsallis -- What entropy at the edge of chaos? / M. Lissia, M. Coraddu and R. Tonelli -- Fractal growth of carbon schwarzites / G. Benedek ... [et al.] -- Clustering and interface propagation in interacting particle dynamics / A. Provata and V. K. Noussiou -- Resonant activation and noise enhanced stability in Josephson junctions / A. L. Pankratov and B. Spagnolo -- Symmetry breaking induced directed motions / C.-H. Chang and T. Y. Tsong -- General theory of Galilean-invariant entropic lattic Boltzmann models / B. M. Boghosian -- Unifying approach to the jamming transition in granular media and

  1. Procuring complex performance

    DEFF Research Database (Denmark)

    Hartmann, A.; Roehrich, J.; Frederiksen, Lars

    2014-01-01

    – The transition towards PCP can be best described as a learning process which cumulates the knowledge and experience in the client-supplier interaction accompanied by changing contractual and relational capabilities. In public infrastructure this process is not initially motivated by the benefits of value co......Purpose – The paper analyses how public buyers transition from procuring single products and services to procuring complex performance (PCP). The aim is to examine the change in the interactions between buyer and supplier, the emergence of value co-creation and the capability development during...... the transition process. Design/methodology/approach – A multiple, longitudinal case study method is used to examine the transition towards PCP. The study deploys rich qualitative data sets by combining semi-structured interviews, focus group meetings and organisational reports and documents. Findings...

  2. Iridium complexes for electrocatalysis

    Energy Technology Data Exchange (ETDEWEB)

    Sheehan, Stafford Wheeler; Hintermair, Ulrich; Thomsen, Julianne M; Brudvig, Gary W; Crabtree, Robert H

    2017-10-17

    Solution-phase (e.g., homogeneous) or surface-immobilized (e.g., heterogeneous) electrode-driven oxidation catalysts based on iridium coordination compounds which self-assemble upon chemical or electrochemical oxidation of suitable precursors and methods of making and using thereof are. Iridium species such as {[Ir(LX).sub.x(H.sub.2O).sub.y(.mu.-O)].sub.z.sup.m+}.sub.n wherein x, y, m are integers from 0-4, z and n from 1-4 and LX is an oxidation-resistant chelate ligand or ligands, such as such as 2(2-pyridyl)-2-propanolate, form upon oxidation of various molecular iridium complexes, for instance [Cp*Ir(LX)OH] or [(cod)Ir(LX)] (Cp*=pentamethylcyclopentadienyl, cod=cis-cis,1,5-cyclooctadiene) when exposed to oxidative conditions, such as sodium periodate (NaIO.sub.4) in aqueous solution at ambient conditions.

  3. Turbulence in complex terrain

    Energy Technology Data Exchange (ETDEWEB)

    Mann, Jakob [Risoe National Lab., Wind Energy and Atmosheric Physics Dept., Roskilde (Denmark)

    1999-03-01

    The purpose of this work is to develop a model of the spectral velocity-tensor in neutral flow over complex terrain. The resulting equations are implemented in a computer code using the mean flow generated by a linear mean flow model as input. It estimates turbulence structure over hills (except on the lee side if recirculation is present) in the so-called outer layer and also models the changes in turbulence statistics in the vicinity roughness changes. The generated turbulence fields are suitable as input for dynamic load calculations on wind turbines and other tall structures and is under implementation in the collection of programs called WA{sup s}P Engineering. (au) EFP-97; EU-JOULE-3. 15 refs.

  4. Complex pendulum biomass sensor

    Science.gov (United States)

    Hoskinson, Reed L.; Kenney, Kevin L.; Perrenoud, Ben C.

    2007-12-25

    A complex pendulum system biomass sensor having a plurality of pendulums. The plurality of pendulums allow the system to detect a biomass height and density. Each pendulum has an angular deflection sensor and a deflector at a unique height. The pendulums are passed through the biomass and readings from the angular deflection sensors are fed into a control system. The control system determines whether adjustment of machine settings is appropriate and either displays an output to the operator, or adjusts automatically adjusts the machine settings, such as the speed, at which the pendulums are passed through the biomass. In an alternate embodiment, an entanglement sensor is also passed through the biomass to determine the amount of biomass entanglement. This measure of entanglement is also fed into the control system.

  5. Complexity Science for Simpletons

    Directory of Open Access Journals (Sweden)

    Feinstein C. A.

    2006-07-01

    Full Text Available In this article, we shall describe some of the most interesting topics in the subject of Complexity Science for a general audience. Anyone with a solid foundation in high school mathematics (with some calculus and an elementary understanding of computer programming will be able to follow this article. First, we shall explain the significance of the P versus NP problem and solve it. Next, we shall describe two other famous mathematics problems, the Collatz 3n+ 1 Conjecture and the Riemann Hypothesis, and show how both Chaitin’s incompleteness theorem and Wolfram’s notion of “computational irreducibility” are important for understanding why no one has, as of yet, solved these two problems.

  6. Complex geometries in wood

    DEFF Research Database (Denmark)

    Tamke, Martin; Ramsgaard Thomsen, Mette; Riiber Nielsen, Jacob

    2009-01-01

    The versatility of wood constructions and traditional wood joints for the production of non standard elements was in focus of a design based research. Herein we established a seamless process from digital design to fabrication. A first research phase centered on the development of a robust parame...... parametric model and a generic design language a later explored the possibilities to construct complex shaped geometries with self registering joints on modern wood crafting machines. The research was carried out as collaboration with industrial partners.......The versatility of wood constructions and traditional wood joints for the production of non standard elements was in focus of a design based research. Herein we established a seamless process from digital design to fabrication. A first research phase centered on the development of a robust...

  7. Segmentation of complex document

    Directory of Open Access Journals (Sweden)

    Souad Oudjemia

    2014-06-01

    Full Text Available In this paper we present a method for segmentation of documents image with complex structure. This technique based on GLCM (Grey Level Co-occurrence Matrix used to segment this type of document in three regions namely, 'graphics', 'background' and 'text'. Very briefly, this method is to divide the document image, in block size chosen after a series of tests and then applying the co-occurrence matrix to each block in order to extract five textural parameters which are energy, entropy, the sum entropy, difference entropy and standard deviation. These parameters are then used to classify the image into three regions using the k-means algorithm; the last step of segmentation is obtained by grouping connected pixels. Two performance measurements are performed for both graphics and text zones; we have obtained a classification rate of 98.3% and a Misclassification rate of 1.79%.

  8. Evolution of Biological Complexity

    Science.gov (United States)

    Goldstein, Raymond E.

    It is a general rule of nature that larger organisms are more complex, at least as measured by the number of distinct types of cells present. This reflects the fitness advantage conferred by a division of labor among specialized cells over homogeneous totipotency. Yet, increasing size has both costs and benefits, and the search for understanding the driving forces behind the evolution of multicellularity is becoming a very active area of research. This article presents an overview of recent experimental and theoretical work aimed at understanding this biological problem from the perspective of physics. For a class of model organisms, the Volvocine green algae, an emerging hypothesis connects the transition from organisms with totipotent cells to those with terminal germ-soma differentiation to the competition between diffusion and fluid advection created by beating flagella. A number of challenging problems in fluid dynamics, nonlinear dynamics, and control theory emerge when one probes the workings of the simplest multicellular organisms.

  9. Complex Hamiltonian Dynamics

    CERN Document Server

    Bountis, Tassos

    2012-01-01

    This book introduces and explores modern developments in the well established field of Hamiltonian dynamical systems. It focuses on high degree-of-freedom systems and the transitional regimes between regular and chaotic motion. The role of nonlinear normal modes is highlighted and the importance of low-dimensional tori in the resolution of the famous FPU paradox is emphasized. Novel powerful numerical methods are used to study localization phenomena and distinguish order from strongly and weakly chaotic regimes. The emerging hierarchy of complex structures in such regimes gives rise to particularly long-lived patterns and phenomena called quasi-stationary states, which are explored in particular in the concrete setting of one-dimensional Hamiltonian lattices and physical applications in condensed matter systems.  The self-contained and pedagogical approach is blended with a unique balance between mathematical rigor, physics insights and concrete applications. End of chapter exercises and (more demanding) res...

  10. Thermodynamics of complexity

    DEFF Research Database (Denmark)

    Westerhoff, Hans V.; Jensen, Peter Ruhdal; Snoep, Jacky L.

    1998-01-01

    Thermodynamics has always been a remarkable science in that it studies macroscopic properties that are only partially determined by the properties of individual molecules. Entropy and free energy only exist in constellations of more than a single molecule (degree of freedom). They are the so...... understanding of this BioComplexity, modem thermodynamic concepts and methods (nonequilibrium thermodynamics, metabolic and hierarchical control analysis) will be needed. We shall propose to redefine nonequilibrium thermodynamics as: The science that aims at understanding the behaviour of nonequilibrium systems...... by taking into account both the molecular properties and the emergent properties that are due to (dys)organisation. This redefinition will free nonequilibrium thermodynamics from the limitations imposed by earlier near-equilibrium assumptions, resolve the duality with kinetics, and bridge the apparent gap...

  11. Complex wounds Feridas complexas

    Directory of Open Access Journals (Sweden)

    Marcus Castro Ferreira

    2006-01-01

    Full Text Available Complex wound is the term used more recently to group those well-known difficult wounds, either chronic or acute, that challenge medical and nursing teams. They defy cure using conventional and simple "dressings" therapy and currently have a major socioeconomic impact. The purpose of this review is to bring these wounds to the attention of the health-care community, suggesting that they should be treated by multidisciplinary teams in specialized hospital centers. In most cases, surgical treatment is unavoidable, because the extent of skin and subcutaneous tissue loss requires reconstruction with grafts and flaps. New technologies, such as the negative pressure device, should be introduced. A brief review is provided of the major groups of complex wounds-diabetic wounds, pressure sores, chronic venous ulcers, post-infection soft-tissue gangrenes, and ulcers resulting from vasculitis.Ferida complexa é uma nova definição para identificar aquelas feridas crônicas e algumas agudas já bem conhecidas e que desafiam equipes médicas e de enfermagem. São difíceis de serem resolvidas usando tratamentos convencionais e simples curativos. Têm atualmente grande impacto sócio-econômico. Esta revisão procura atrair atenção da comunidade de profissionais de saúde para estas feridas, sugerindo que devam ser tratadas por equipe multidisciplinar em centro hospitalar especializado. Na maioria dos casos o tratamento cirúrgico deve ser indicado, uma vez que a perda de pele e tecido subcutâneo é extensa, necessitando de reconstrução com enxertos e retalhos. Nova tecnologia, como uso da terapia por pressão negativa foi introduzido. Breves comentários sobre os principais grupos de feridas complexas: pé diabético, úlceras por pressão, úlceras venosas, síndrome de Fournier e vasculites.

  12. Binodal Compositions of Polyelectrolyte Complexes

    NARCIS (Netherlands)

    Spruijt, E.; Westphal, A.H.; Borst, J.W.; Cohen Stuart, M.A.; Gucht, van der J.

    2010-01-01

    When oppositely charged polyelectrolytes are mixed below a critical salt concentration, their mixtures show macroscopic phase separation into a dilute and a dense, polyelectrolyte complex phase. Binodal compositions of the polyelectrolyte complexes have been measured experimentally using

  13. Fifteen papers in complex analysis

    CERN Document Server

    Aizenberg, L A; Degtyar', P V; Gindikin, S G; Gaidis, Ya Yu

    1990-01-01

    The papers in this volume range over a variety of topics in complex analysis, including holomorphic and entire functions, integral representations, the local theory of residues, complex manifolds, singularities, and CR structures.

  14. Holistic education and complexity thinking

    OpenAIRE

    Jörg, T.

    2007-01-01

    Paper proposal for the SIG Holistic Education at AERA 2007 Title: Holistic Education and Complexity Thinking Ton Jörg IVLOS Institute of Education University of Utrecht The Netherlands ABSTRACT In this paper I link complexity thinking with Holistic Education (HE). It is a challenge to show how HE may benefit of thinking in complexity. For me thinking in complexity is a way of humanizing our scientific thinking. It asks for a reform of our thinking. The rethinking of com...

  15. Statistic complexity: combining kolmogorov complexity with an ensemble approach.

    Science.gov (United States)

    Emmert-Streib, Frank

    2010-08-26

    The evaluation of the complexity of an observed object is an old but outstanding problem. In this paper we are tying on this problem introducing a measure called statistic complexity. This complexity measure is different to all other measures in the following senses. First, it is a bivariate measure that compares two objects, corresponding to pattern generating processes, on the basis of the normalized compression distance with each other. Second, it provides the quantification of an error that could have been encountered by comparing samples of finite size from the underlying processes. Hence, the statistic complexity provides a statistical quantification of the statement ' is similarly complex as Y'. The presented approach, ultimately, transforms the classic problem of assessing the complexity of an object into the realm of statistics. This may open a wider applicability of this complexity measure to diverse application areas.

  16. Kolmogorov complexity as a language

    CERN Document Server

    Shen, Alexander

    2011-01-01

    The notion of Kolmogorov complexity (=the minimal length of a program that generates some object) is often useful as a kind of language that allows us to reformulate some notions and therefore provide new intuition. In this survey we provide (with minimal comments) many different examples where notions and statements that involve Kolmogorov complexity are compared with their counterparts not involving complexity.

  17. Sequence-controlled RNA self-processing: computational design, biochemical analysis, and visualization by AFM

    Science.gov (United States)

    Petkovic, Sonja; Badelt, Stefan; Flamm, Christoph; Delcea, Mihaela

    2015-01-01

    Reversible chemistry allowing for assembly and disassembly of molecular entities is important for biological self-organization. Thus, ribozymes that support both cleavage and formation of phosphodiester bonds may have contributed to the emergence of functional diversity and increasing complexity of regulatory RNAs in early life. We have previously engineered a variant of the hairpin ribozyme that shows how ribozymes may have circularized or extended their own length by forming concatemers. Using the Vienna RNA package, we now optimized this hairpin ribozyme variant and selected four different RNA sequences that were expected to circularize more efficiently or form longer concatemers upon transcription. (Two-dimensional) PAGE analysis confirms that (i) all four selected ribozymes are catalytically active and (ii) high yields of cyclic species are obtained. AFM imaging in combination with RNA structure prediction enabled us to calculate the distributions of monomers and self-concatenated dimers and trimers. Our results show that computationally optimized molecules do form reasonable amounts of trimers, which has not been observed for the original system so far, and we demonstrate that the combination of theoretical prediction, biochemical and physical analysis is a promising approach toward accurate prediction of ribozyme behavior and design of ribozymes with predefined functions. PMID:25999318

  18. Sequence-controlled RNA self-processing: computational design, biochemical analysis, and visualization by AFM.

    Science.gov (United States)

    Petkovic, Sonja; Badelt, Stefan; Block, Stephan; Flamm, Christoph; Delcea, Mihaela; Hofacker, Ivo; Müller, Sabine

    2015-07-01

    Reversible chemistry allowing for assembly and disassembly of molecular entities is important for biological self-organization. Thus, ribozymes that support both cleavage and formation of phosphodiester bonds may have contributed to the emergence of functional diversity and increasing complexity of regulatory RNAs in early life. We have previously engineered a variant of the hairpin ribozyme that shows how ribozymes may have circularized or extended their own length by forming concatemers. Using the Vienna RNA package, we now optimized this hairpin ribozyme variant and selected four different RNA sequences that were expected to circularize more efficiently or form longer concatemers upon transcription. (Two-dimensional) PAGE analysis confirms that (i) all four selected ribozymes are catalytically active and (ii) high yields of cyclic species are obtained. AFM imaging in combination with RNA structure prediction enabled us to calculate the distributions of monomers and self-concatenated dimers and trimers. Our results show that computationally optimized molecules do form reasonable amounts of trimers, which has not been observed for the original system so far, and we demonstrate that the combination of theoretical prediction, biochemical and physical analysis is a promising approach toward accurate prediction of ribozyme behavior and design of ribozymes with predefined functions. © 2015 Petkovic et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  19. Managing complexity of aerospace systems

    Science.gov (United States)

    Tamaskar, Shashank

    Growing complexity of modern aerospace systems has exposed the limits of conventional systems engineering tools and challenged our ability to design them in a timely and cost effective manner. According to the US Government Accountability Office (GAO), in 2009 nearly half of the defense acquisition programs are expecting 25% or more increase in unit acquisition cost. Increase in technical complexity has been identified as one of the primary drivers behind cost-schedule overruns. Thus to assure the affordability of future aerospace systems, it is increasingly important to develop tools and capabilities for managing their complexity. We propose an approach for managing the complexity of aerospace systems to address this pertinent problem. To this end, we develop a measure that improves upon the state-of-the-art metrics and incorporates key aspects of system complexity. We address the problem of system decomposition by presenting an algorithm for module identification that generates modules to minimize integration complexity. We demonstrate the framework on diverse spacecraft and show the impact of design decisions on integration cost. The measure and the algorithm together help the designer track and manage complexity in different phases of system design. We next investigate how complexity can be used as a decision metric in the model-based design (MBD) paradigm. We propose a framework for complexity enabled design space exploration that introduces the idea of using complexity as a non-traditional design objective. We also incorporate complexity with the component based design paradigm (a sub-field of MBD) and demonstrate it on several case studies. The approach for managing complexity is a small but significant contribution to the vast field of complexity management. We envision our approach being used in concert with a suite of complexity metrics to provide an ability to measure and track complexity through different stages of design and development. This will not

  20. A geometric approach to complexity.

    Science.gov (United States)

    Ay, Nihat; Olbrich, Eckehard; Bertschinger, Nils; Jost, Jürgen

    2011-09-01

    We develop a geometric approach to complexity based on the principle that complexity requires interactions at different scales of description. Complex systems are more than the sum of their parts of any size and not just more than the sum of their elements. Using information geometry, we therefore analyze the decomposition of a system in terms of an interaction hierarchy. In mathematical terms, we present a theory of complexity measures for finite random fields using the geometric framework of hierarchies of exponential families. Within our framework, previously proposed complexity measures find their natural place and gain a new interpretation.

  1. Monotone measures of statistical complexity

    Energy Technology Data Exchange (ETDEWEB)

    Rudnicki, Łukasz [Institute for Physics, University of Freiburg, Rheinstraße 10, D-79104 Freiburg (Germany); Center for Theoretical Physics, Polish Academy of Sciences, Aleja Lotników 32/46, PL-02-668 Warsaw (Poland); Toranzo, Irene V. [Instituto Carlos I de Física Teórica y Computacional, Universidad de Granada, 18071-Granada (Spain); Departamento de Física Atómica, Molecular y Nuclear, Universidad de Granada, 18071-Granada (Spain); Sánchez-Moreno, Pablo [Instituto Carlos I de Física Teórica y Computacional, Universidad de Granada, 18071-Granada (Spain); Departamento de Matemática Aplicada, Universidad de Granada, 18071-Granada (Spain); Dehesa, Jesús S., E-mail: dehesa@ugr.es [Instituto Carlos I de Física Teórica y Computacional, Universidad de Granada, 18071-Granada (Spain); Departamento de Física Atómica, Molecular y Nuclear, Universidad de Granada, 18071-Granada (Spain)

    2016-01-28

    Highlights: • The notion of monotonicity of the complexity measure of a probability distribution is introduced and discussed. • The monotonicity properties of statistical measures of complexity are studied. • The Cramer–Rao and Fisher–Shannon measures of complexity are shown to be monotone. - Abstract: We introduce and discuss the notion of monotonicity for the complexity measures of general probability distributions, patterned after the resource theory of quantum entanglement. Then, we explore whether this property is satisfied by the three main intrinsic measures of complexity (Crámer–Rao, Fisher–Shannon, LMC) and some of their generalizations.

  2. On Measuring the Complexity of Networks: Kolmogorov Complexity versus Entropy

    Directory of Open Access Journals (Sweden)

    Mikołaj Morzy

    2017-01-01

    Full Text Available One of the most popular methods of estimating the complexity of networks is to measure the entropy of network invariants, such as adjacency matrices or degree sequences. Unfortunately, entropy and all entropy-based information-theoretic measures have several vulnerabilities. These measures neither are independent of a particular representation of the network nor can capture the properties of the generative process, which produces the network. Instead, we advocate the use of the algorithmic entropy as the basis for complexity definition for networks. Algorithmic entropy (also known as Kolmogorov complexity or K-complexity for short evaluates the complexity of the description required for a lossless recreation of the network. This measure is not affected by a particular choice of network features and it does not depend on the method of network representation. We perform experiments on Shannon entropy and K-complexity for gradually evolving networks. The results of these experiments point to K-complexity as the more robust and reliable measure of network complexity. The original contribution of the paper includes the introduction of several new entropy-deceiving networks and the empirical comparison of entropy and K-complexity as fundamental quantities for constructing complexity measures for networks.

  3. Complex Sleep Apnea Syndrome

    Directory of Open Access Journals (Sweden)

    Muhammad Talha Khan

    2014-01-01

    Full Text Available Complex sleep apnea is the term used to describe a form of sleep disordered breathing in which repeated central apneas (>5/hour persist or emerge when obstructive events are extinguished with positive airway pressure (PAP and for which there is not a clear cause for the central apneas such as narcotics or systolic heart failure. The driving forces in the pathophysiology are felt to be ventilator instability associated oscillation in PaCO2 arterial partial pressure of Carbon Dioxide, continuous cositive airway pressure (CPAP related increased CO2 carbon dioxide elimination, and activation of airway and pulmonary stretch receptors triggering these central apneas. The prevalence ranges from 0.56% to 18% with no clear predictive characteristics as compared to simple obstructive sleep apnea. Prognosis is similar to obstructive sleep apnea. The central apnea component in most patients on followup using CPAP therap, has resolved. For those with continued central apneas on simple CPAP therapy, other treatment options include bilevel PAP, adaptive servoventilation, permissive flow limitation and/or drugs.

  4. Information Complexity and Biology

    Science.gov (United States)

    Bagnoli, Franco; Bignone, Franco A.; Cecconi, Fabio; Politi, Antonio

    Kolmogorov contributed directly to Biology in essentially three problems: the analysis of population dynamics (Lotka-Volterra equations), the reaction-diffusion formulation of gene spreading (FKPP equation), and some discussions about Mendel's laws. However, the widely recognized importance of his contribution arises from his work on algorithmic complexity. In fact, the limited direct intervention in Biology reflects the generally slow growth of interest of mathematicians towards biological issues. From the early work of Vito Volterra on species competition, to the slow growth of dynamical systems theory, contributions to the study of matter and the physiology of the nervous system, the first 50-60 years have witnessed important contributions, but as scattered pieces apparently uncorrelated, and in branches often far away from Biology. Up to the 40' it is hard to see the initial loose build up of a convergence, for those theories that will become mainstream research by the end of the century, and connected by the study of biological systems per-se.

  5. Complexity a very short introduction

    CERN Document Server

    Holland, John H

    2014-01-01

    The importance of complexity is well-captured by Hawking's comment: "Complexity is the science of the 21st century". From the movement of flocks of birds to the Internet, environmental sustainability, and market regulation, the study and understanding of complex non-linear systems has become highly influential over the last 30 years. In this Very Short Introduction, one of the leading figures in the field, John Holland, introduces the key elements and conceptual framework of complexity. From complex physical systems such as fluid flow and the difficulties of predicting weather, to complex adaptive systems such as the highly diverse and interdependent ecosystems of rainforests, he combines simple, well-known examples - Adam Smith's pin factory, Darwin's comet orchid, and Simon's 'watchmaker' - with an account of the approaches, involving agents and urn models, taken by complexity theory. ABOUT THE SERIES: The Very Short Introductions series from Oxford University Press contains hundreds of titles in almost eve...

  6. Complexity measurement based on information theory and kolmogorov complexity.

    Science.gov (United States)

    Lui, Leong Ting; Terrazas, Germán; Zenil, Hector; Alexander, Cameron; Krasnogor, Natalio

    2015-01-01

    In the past decades many definitions of complexity have been proposed. Most of these definitions are based either on Shannon's information theory or on Kolmogorov complexity; these two are often compared, but very few studies integrate the two ideas. In this article we introduce a new measure of complexity that builds on both of these theories. As a demonstration of the concept, the technique is applied to elementary cellular automata and simulations of the self-organization of porphyrin molecules.

  7. Spatiotemporal Imaging of Complexity

    Directory of Open Access Journals (Sweden)

    Stephen Ellis Robinson

    2013-01-01

    Full Text Available What are the functional neuroimaging measurements required for more fully characterizing the events and locations of neocortical activity? A prime assumption has been that modulation of cortical activity will inevitably be reflected in changes in energy utilization (for the most part changes of glucose and oxygen consumption. Are such a measures complete and sufficient? More direct measures of cortical electrophysiological activity show event or task-related modulation of amplitude or band-limited oscillatory power. Using magnetoencephalography (MEG, these measures have been shown to correlate well with energy utilization sensitive BOLD fMRI. In this paper, we explore the existence of state changes in electrophysiological cortical activity that can occur independently of changes in averaged amplitude, source power or indices of metabolic rates. In addition, we demonstrate that such state changes can be described by applying a new measure of complexity, rank vector entropy (RVE, to source waveform estimates from beamformer-processed MEG. RVE is a non-parametric symbolic dynamic informational entropy measure that accommodates the wide dynamic range of measured brain signals while resolving its temporal variations. By representing the measurements by their rank values, RVE overcomes the problem of defining embedding space partitions without resorting to signal compression. This renders RVE independent of absolute signal amplitude. In addition, this approach is robust, being relatively free of tunable parameters. We present examples of task-free and task dependent MEG demonstrating that RVE provides new information by uncovering hidden dynamical struc-ture in the apparent turbulent (or chaotic dynamics of spontaneous cortical activity.

  8. Carney complex (CNC

    Directory of Open Access Journals (Sweden)

    Bertherat Jérôme

    2006-06-01

    Full Text Available Abstract The Carney complex (CNC is a dominantly inherited syndrome characterized by spotty skin pigmentation, endocrine overactivity and myxomas. Skin pigmentation anomalies include lentigines and blue naevi. The most common endocrine gland manifestations are acromegaly, thyroid and testicular tumors, and adrenocorticotropic hormone (ACTH-independent Cushing's syndrome due to primary pigmented nodular adrenocortical disease (PPNAD. PPNAD, a rare cause of Cushing's syndrome, is due to primary bilateral adrenal defect that can be also observed in some patients without other CNC manifestations or familial history of the disease. Myxomas can be observed in the heart, skin and breast. Cardiac myxomas can develop in any cardiac chamber and may be multiple. One of the putative CNC genes located on 17q22-24, (PRKAR1A, has been identified to encode the regulatory subunit (R1A of protein kinase A. Heterozygous inactivating mutations of PRKAR1A were reported initially in 45 to 65 % of CNC index cases, and may be present in about 80 % of the CNC families presenting mainly with Cushing's syndrome. PRKAR1A is a key component of the cAMP signaling pathway that has been implicated in endocrine tumorigenesis and could, at least partly, function as a tumor suppressor gene. Genetic analysis should be proposed to all CNC index cases. Patients with CNC or with a genetic predisposition to CNC should have regular screening for manifestations of the disease. Clinical work-up for all the manifestations of CNC should be performed at least once a year in all patients and should start in infancy. Cardiac myxomas require surgical removal. Treatment of the other manifestations of CNC should be discussed and may include follow-up, surgery, or medical treatment depending on the location of the tumor, its size, the existence of clinical signs of tumor mass or hormonal excess, and the suspicion of malignancy. Bilateral adrenalectomy is the most common treatment for Cushing

  9. Carney complex (CNC).

    Science.gov (United States)

    Bertherat, Jérôme

    2006-06-06

    The Carney complex (CNC) is a dominantly inherited syndrome characterized by spotty skin pigmentation, endocrine overactivity and myxomas. Skin pigmentation anomalies include lentigines and blue naevi. The most common endocrine gland manifestations are acromegaly, thyroid and testicular tumors, and adrenocorticotropic hormone (ACTH)-independent Cushing's syndrome due to primary pigmented nodular adrenocortical disease (PPNAD). PPNAD, a rare cause of Cushing's syndrome, is due to primary bilateral adrenal defect that can be also observed in some patients without other CNC manifestations or familial history of the disease. Myxomas can be observed in the heart, skin and breast. Cardiac myxomas can develop in any cardiac chamber and may be multiple. One of the putative CNC genes located on 17q22-24, (PRKAR1A), has been identified to encode the regulatory subunit (R1A) of protein kinase A. Heterozygous inactivating mutations of PRKAR1A were reported initially in 45 to 65% of CNC index cases, and may be present in about 80% of the CNC families presenting mainly with Cushing's syndrome. PRKAR1A is a key component of the cAMP signaling pathway that has been implicated in endocrine tumorigenesis and could, at least partly, function as a tumor suppressor gene. Genetic analysis should be proposed to all CNC index cases. Patients with CNC or with a genetic predisposition to CNC should have regular screening for manifestations of the disease. Clinical work-up for all the manifestations of CNC should be performed at least once a year in all patients and should start in infancy. Cardiac myxomas require surgical removal. Treatment of the other manifestations of CNC should be discussed and may include follow-up, surgery, or medical treatment depending on the location of the tumor, its size, the existence of clinical signs of tumor mass or hormonal excess, and the suspicion of malignancy. Bilateral adrenalectomy is the most common treatment for Cushing's syndrome due to PPNAD.

  10. Increasing complexity with quantum physics.

    Science.gov (United States)

    Anders, Janet; Wiesner, Karoline

    2011-09-01

    We argue that complex systems science and the rules of quantum physics are intricately related. We discuss a range of quantum phenomena, such as cryptography, computation and quantum phases, and the rules responsible for their complexity. We identify correlations as a central concept connecting quantum information and complex systems science. We present two examples for the power of correlations: using quantum resources to simulate the correlations of a stochastic process and to implement a classically impossible computational task.

  11. How to lead complex situations

    DEFF Research Database (Denmark)

    Hansen, Michael Pingel

    2013-01-01

    The military leader is experiencing increasingly more complex situations, whether it is as leader in a foreign combat environment or in the home-based public administration. Complex situations like these call for a special set of managerial responses and a special way of leading organisations....... The proposition of this article is that the methods that drive innovative processes, strengthening the creative culture, are necessary to manage complex situations in military contexts....

  12. Complexity of Terminating Preference Elicitation

    OpenAIRE

    Walsh, Toby

    2009-01-01

    Complexity theory is a useful tool to study computational issues surrounding the elicitation of preferences, as well as the strategic manipulation of elections aggregating together preferences of multiple agents. We study here the complexity of determining when we can terminate eliciting preferences, and prove that the complexity depends on the elicitation strategy. We show, for instance, that it may be better from a computational perspective to elicit all preferences from one agent at a time...

  13. Bell Inequalities for Complex Networks

    Science.gov (United States)

    2015-10-26

    AFRL-AFOSR-VA-TR-2015-0355 YIP Bell Inequalities for Complex Networks Greg Ver Steeg UNIVERSITY OF SOUTHERN CALIFORNIA LOS ANGELES Final Report 10/26...performance report PI: Greg Ver Steeg Young Investigator Award Grant Title: Bell Inequalities for Complex Networks Grant #: FA9550-12-1-0417 Reporting...October 20, 2015 Final Report for “Bell Inequalities for Complex Networks” Greg Ver Steeg Abstract This effort studied new methods to understand the effect

  14. Bufferless transmission in complex networks

    OpenAIRE

    Pu, Cunlai; Cui, Wei; Wu, Jiexin; Yang, Jian

    2017-01-01

    Complex bufferless networks such as on-chip networks and optical burst switching networks haven't been paid enough attention in network science. In complex bufferless networks, the store and forward mechanism is not applicable, since the network nodes are not allowed to buffer data packets. In this paper, we study the data transmission process in complex bufferless networks from the perspective of network science. Specifically, we use the Price model to generate the underlying network topolog...

  15. Complexity in de Sitter space

    Science.gov (United States)

    Reynolds, Alan P.; Ross, Simon F.

    2017-09-01

    We consider the holographic complexity conjectures for de-Sitter invariant states in a quantum field theory on de Sitter space, dual to asymptotically anti-de Sitter geometries with de Sitter boundaries. The bulk holographic duals include solutions with or without a horizon. If we compute the complexity from the spatial volume, we find results consistent with general expectations, but the conjectured bound on the growth rate is not saturated. If we compute complexity from the action of the Wheeler-de Witt patch, we find qualitative differences from the volume calculation, with states of smaller energy having larger complexity than those of larger energy, even though the latter have bulk horizons.

  16. Quantitative assessment of increasing complexity

    Science.gov (United States)

    Csernai, L. P.; Spinnangr, S. F.; Velle, S.

    2017-05-01

    We study the build up of complexity on the example of 1 kg matter in different forms. We start with the simplest example of ideal gases, and then continue with more complex chemical, biological, life, social and technical structures. We assess the complexity of these systems quantitatively, based on their entropy. We present a method to attribute the same entropy to known physical systems and to complex organic molecules, up to a DNA molecule. The important steps in this program and the basic obstacles are discussed.

  17. Technetium-aspirin molecule complexes

    Energy Technology Data Exchange (ETDEWEB)

    El-Shahawy, A.S.; Mahfouz, R.M.; Aly, A.A.M.; El-Zohry, M. (Assiut Univ. (Egypt))

    1993-01-01

    Technetium-aspirin and technetium-aspirin-like molecule complexes were prepared. The structure of N-acetylanthranilic acid (NAA) has been decided through CNDO calculations. The ionization potential and electron affinity of the NAA molecule as well as the charge densities were calculated. The electronic absorption spectra of Tc(V)-Asp and Tc(V)-ATS complexes have two characteristic absorption bands at 450 and 600 nm, but the Tc(V)-NAA spectrum has one characteristic band at 450 nm. As a comparative study, Mo-ATS complex was prepared and its electronic absorption spectrum is comparable with the Tc-ATS complex spectrum. (author).

  18. Complexity leadership: a healthcare imperative.

    Science.gov (United States)

    Weberg, Dan

    2012-01-01

    The healthcare system is plagued with increasing cost and poor quality outcomes. A major contributing factor for these issues is that outdated leadership practices, such as leader-centricity, linear thinking, and poor readiness for innovation, are being used in healthcare organizations. Complexity leadership theory provides a new framework with which healthcare leaders may practice leadership. Complexity leadership theory conceptualizes leadership as a continual process that stems from collaboration, complex systems thinking, and innovation mindsets. Compared to transactional and transformational leadership concepts, complexity leadership practices hold promise to improve cost and quality in health care. © 2012 Wiley Periodicals, Inc.

  19. Measuring Complexity of SAP Systems

    Directory of Open Access Journals (Sweden)

    Ilja Holub

    2016-10-01

    Full Text Available The paper discusses the reasons of complexity rise in ERP system SAP R/3. It proposes a method for measuring complexity of SAP. Based on this method, the computer program in ABAP for measuring complexity of particular SAP implementation is proposed as a tool for keeping ERP complexity under control. The main principle of the measurement method is counting the number of items or relations in the system. The proposed computer program is based on counting of records in organization tables in SAP.

  20. Complex networks an algorithmic perspective

    CERN Document Server

    Erciyes, Kayhan

    2014-01-01

    Network science is a rapidly emerging field of study that encompasses mathematics, computer science, physics, and engineering. A key issue in the study of complex networks is to understand the collective behavior of the various elements of these networks.Although the results from graph theory have proven to be powerful in investigating the structures of complex networks, few books focus on the algorithmic aspects of complex network analysis. Filling this need, Complex Networks: An Algorithmic Perspective supplies the basic theoretical algorithmic and graph theoretic knowledge needed by every r

  1. Sustainability, Complexity and Learning: Insights from Complex Systems Approaches

    Science.gov (United States)

    Espinosa, A.; Porter, T.

    2011-01-01

    Purpose: The purpose of this research is to explore core contributions from two different approaches to complexity management in organisations aiming to improve their sustainability,: the Viable Systems Model (VSM), and the Complex Adaptive Systems (CAS). It is proposed to perform this by summarising the main insights each approach offers to…

  2. Complex Constructivism: A Theoretical Model of Complexity and Cognition

    Science.gov (United States)

    Doolittle, Peter E.

    2014-01-01

    Education has long been driven by its metaphors for teaching and learning. These metaphors have influenced both educational research and educational practice. Complexity and constructivism are two theories that provide functional and robust metaphors. Complexity provides a metaphor for the structure of myriad phenomena, while constructivism…

  3. ComplexRec 2017: Recommendation in Complex Scenarios

    DEFF Research Database (Denmark)

    Recommendation algorithms for ratings prediction and item ranking have steadily matured during the past decade. However, these state-of-the-art algorithms are typically applied in relatively straightforward scenarios. In reality, recommendation is often a more complex problem: it is usually just...... a single step in the user's more complex background need. These background needs can often place a variety of constraints on which recommendations are interesting to the user and when they are appropriate. However, relatively little research has been done on these complex recommendation scenarios....... The ComplexRec 2017 workshop addressed this by providing an interactive venue for discussing approaches to recommendation in complex scenarios that have no simple one-size-fits-all-solution....

  4. Workshop on Recommendation in Complex Scenarios (ComplexRec 2017)

    DEFF Research Database (Denmark)

    Bogers, Toine

    2017-01-01

    Recommendation algorithms for ratings prediction and item ranking have steadily matured during the past decade. However, these state-of-the-art algorithms are typically applied in relatively straightforward scenarios. In reality, recommendation is often a more complex problem: it is usually just...... a single step in the user's more complex background need. These background needs can often place a variety of constraints on which recommendations are interesting to the user and when they are appropriate. However, relatively little research has been done on these complex recommendation scenarios....... The ComplexRec 2017 workshop addressed this by providing an interactive venue for discussing approaches to recommendation in complex scenarios that have no simple one-size-fits-all-solution....

  5. ComplexViewer: visualization of curated macromolecular complexes.

    Science.gov (United States)

    Combe, Colin W; Sivade, Marine Dumousseau; Hermjakob, Henning; Heimbach, Joshua; Meldal, Birgit H M; Micklem, Gos; Orchard, Sandra; Rappsilber, Juri

    2017-11-15

    Proteins frequently function as parts of complexes, assemblages of multiple proteins and other biomolecules, yet network visualizations usually only show proteins as parts of binary interactions. ComplexViewer visualizes interactions with more than two participants and thereby avoids the need to first expand these into multiple binary interactions. Furthermore, if binding regions between molecules are known then these can be displayed in the context of the larger complex. freely available under Apache version 2 license; EMBL-EBI Complex Portal: http://www.ebi.ac.uk/complexportal; Source code: https://github.com/MICommunity/ComplexViewer; Package: https://www.npmjs.com/package/complexviewer; http://biojs.io/d/complexviewer. Language: JavaScript; Web technology: Scalable Vector Graphics; Libraries: D3.js. colin.combe@ed.ac.uk or juri.rappsilber@ed.ac.uk.

  6. Team dynamics in complex projects

    NARCIS (Netherlands)

    Oeij, P.; Vroome, E.E.M. de; Dhondt, S.; Gaspersz, J.B.R.

    2012-01-01

    Complexity of projects is hotly debated and a factor which affects innovativeness of team performance. Much attention in the past is paid to technical complexity and many issues are related to natural and physical sciences. A growing awareness of the importance of socioorganisational issues is

  7. Electrochemical analysis of metal complexes

    NARCIS (Netherlands)

    Jong, de H.G.

    1987-01-01

    The present study is concerned with the electroanalytical chemistry of complexes of metals with large ligands. The main purpose was to develop quantitative descriptions of the voltammetric current-potential relation of metal complex systems with different diffusion coefficients of the

  8. Complex Variables throughout the Curriculum

    Science.gov (United States)

    D'Angelo, John P.

    2017-01-01

    We offer many specific detailed examples, several of which are new, that instructors can use (in lecture or as student projects) to revitalize the role of complex variables throughout the curriculum. We conclude with three primary recommendations: revise the syllabus of Calculus II to allow early introductions of complex numbers and linear…

  9. TETRACYANONICKELATE(II) PYRIDAZINE COMPLEXES

    African Journals Online (AJOL)

    B. S. Chandravanshi

    and their structures consist of polymeric layers of │M−Ni(CN)4│∞ with the pdz bound to the metal (M) atom. KEY WORDS: Hofmann-type complexes, Vibrational spectra, Pyridazine, Tetracyanonickelate(II), Thermal analysis. INTRODUCTION. Cyano-bridged complexes have been shown to form polymeric structures by ...

  10. COMPLEXES WITH AN ANTIRETROVIRAL DRUG

    African Journals Online (AJOL)

    biology. Chem. Rev. 1996, 96, 2239-2314. 7. Refat, M.S.; Sharshar, T.; Elsabawy, K.M.; Heiba, Z.K. Physicochemical impact studies of gamma rays on “aspirin” analgesics drug and its metal complexes in solid form: Synthesis, spectroscopic and biological assessment of Ca(II), Mg(II), Sr(II) and Ba(II) aspirinate complexes.

  11. Servitization, Services and Managing Complexity

    DEFF Research Database (Denmark)

    Harjo, Ieva; Frandsen, Thomas; Hsuan, Juliana

    This paper explores how seemingly complex servitized solutions can become tradable in a customer–supplier relationship by objectification and abbreviation. The key argument is that the complexity of product-service solutions can be reduced by abbreviation of the reality in written form of contracts...

  12. Tuberous sclerosis complex in autism.

    Science.gov (United States)

    Guo, Xin; Tu, Wen-Jun; Shi, Xiao-Dong

    2012-09-01

    To study the prevalence rate of tuberous sclerosis complex in autistic disorder. We studied one cohort of children followed up since 2005 until 2009, with autistic disorder, to determine the incidence of tuberous sclerosis complex. We established an autistic disorder registry in 2005 at China Rehabilitation Research Center. During the 4-year period (2005-2009), we collected a database of 429 children (390 boys and 39 girls; male to female ratio 10:1) with autistic disorder and pervasive developmental disorders. We routinely examined all children with autistic disorder for any features of tuberous sclerosis complex by looking for neurocutaneous markers such as depigmented spots. In those with infantile spasm or epilepsy, the clinical features of tuberous sclerosis complex were monitored regularly during follow-up. Of these, five had tuberous sclerosis complex. Thus, the prevalence rate of tuberous sclerosis complex in autistic disorder is 1.17%. All of these children were mentally retarded with moderate to severe grades. Their IQ or developmental quotient was less than 70. The prevalence rate of tuberous sclerosis complex in autistic disorder was 1.17% in our region; autism spectrum disorder is a condition that might be associated with development of tuberous sclerosis complex.

  13. Rhythmic complexity and predictive coding

    DEFF Research Database (Denmark)

    Vuust, Peter; Witek, Maria A G

    2014-01-01

    Musical rhythm, consisting of apparently abstract intervals of accented temporal events,has a remarkable capacity to move our minds and bodies. How does the cognitive systemenable our experiences of rhythmically complex music? In this paper, we describe somecommon forms of rhythmic complexity in ...

  14. Complex multiplication of abelian surfaces

    NARCIS (Netherlands)

    Streng, Theodorus Cornelis

    2010-01-01

    The theory of complex multiplication makes it possible to construct certain class fields and abelian varieties. The main theme of this thesis is making these constructions explicit for the case where the abelian varieties have dimension 2. Chapter I is an introduction to complex

  15. ZIRCONIUM (IV) COMPLEXES WITH SOME ...

    African Journals Online (AJOL)

    DR. AMINU

    Department of Pure and Industrial Chemistry, Bayero University, P.M.B. 3011, Kano – Nigeria e-mail: jnaaliya@yahoo.com ... infrared spectra, elemental analysis and other properties suggest that the complexes are six coordinate. The schiff bases .... and qualitative analysis data of the complexes. Therefore the catalytic ...

  16. Understanding and Teaching Complex Texts

    Science.gov (United States)

    Fisher, Douglas; Frey, Nancy

    2014-01-01

    Teachers in today's classrooms struggle every day to design instructional interventions that would build students' reading skills and strategies in order to ensure their comprehension of complex texts. Text complexity can be determined in both qualitative and quantitative ways. In this article, the authors describe various innovative…

  17. Complexes and aggregates of chlorophylls

    NARCIS (Netherlands)

    Kooyman, R.P.H.

    1980-01-01

    Chlorophyll (Chl) molecules can form complexes in two important ways: by ligation at the magnesium atom and/or by hydrogen bonding at the keto- carbonyl group. Under certain conditions these processes may give rise to dimer formation. This thesis describes some properties of complexes and dimers of

  18. Holistic education and complexity thinking

    NARCIS (Netherlands)

    Jörg, T.

    2007-01-01

    Paper proposal for the SIG Holistic Education at AERA 2007 Title: Holistic Education and Complexity Thinking Ton Jörg IVLOS Institute of Education University of Utrecht The Netherlands A.G.D.Jorg@ivlos.uu.nl ABSTRACT In this paper I link complexity thinking with Holistic Education (HE). It is a

  19. complexes of Mannich base ligands

    Indian Academy of Sciences (India)

    Unknown

    elemental analysis, electrochemical and electron paramagnetic spectral studies. Redox properties of the complexes in acetonitrile are highly quasireversible due to the chemical or/and stereochemical changes subsequent to electron transfer. The complexes show resolved copper hyperfine EPR at room temperature, ...

  20. Holographic complexity and spacetime singularities

    Energy Technology Data Exchange (ETDEWEB)

    Barbón, José L.F. [Instituto de Física Teórica IFT UAM/CSIC,C/ Nicolás Cabrera 13, Campus Universidad Autónoma de Madrid,Madrid 28049 (Spain); Rabinovici, Eliezer [Racah Institute of Physics, The Hebrew University,Jerusalem 91904 (Israel); Laboratoire de Physique Théorique et Hautes Energies, Université Pierre et Marie Curie, 4 Place Jussieu, 75252 Paris Cedex 05 (France)

    2016-01-15

    We study the evolution of holographic complexity in various AdS/CFT models containing cosmological crunch singularities. We find that a notion of complexity measured by extremal bulk volumes tends to decrease as the singularity is approached in CFT time, suggesting that the corresponding quantum states have simpler entanglement structure at the singularity.

  1. Intermittency in Complex Flows

    Science.gov (United States)

    Ben Mahjoub, Otman; Redondo, Jose M.

    2017-04-01

    Experimental results of the complex turbulent wake of a cilinder in 2D [1] and 3D flows [2] were used to investigate the scaling of structure functions, similar research was also performed on wave propagation and breaking in the Ocean [3], in the the stratified Atmosphere (ABL) [4] and in a 100large flume (UPC) for both regular and irregular waves, where long time series of waves propagating and generating breaking turbulence velocity rms and higher order measurements were taken in depth. [3,5] by means of a velocimeter SONTEK3-D. The probability distribution functions of the velocity differences and their non Gaussian distribution related to the energy spectrum indicate that irregularity is an important source of turbulence. From Kolmogorov's K41 and K61 intermittency correction: the p th-order longitudinal velocity structure function δul at scale l in the inertial range of three-dimensional fully developed turbulence is related by ⟨δup⟩ = ⟨(u(x+ l)- u(x))p⟩ ˜ ɛp0/3lp/3 l where ⟨...⟩ represents the spatial average over flow domain, with ɛ0 the mean energy dissipation per unit mass and l is the separation distance. The importance of the random nature of the energy dissipation led to the K62 theory of intermittency, but locality and non-homogeneity are key issues. p p/3 p/3 ξd ⟨δul⟩ ˜ ⟨ɛl ⟩l ˜ l and ξp = p 3 + τp/3 , where now ɛl is a fractal energy dissipation at scale l, τp/3 is the scaling of and ξp is the scaling exponent of the velocity structure function of order p. Both in K41 and K62, the structure functions of third order related to skewness is ξ3 = 1. But this is not true either. We show that scaling exponents ξp do deviate from early studies that only investigated homogeneous turbulence, where a large inertial range dominates. The use of multi-fractal analysis and improvements on Structure function calculations on standard Enhanced mixing is an essential property of turbulence and efforts to alter and to control

  2. COMPLEX TRAINING: A BRIEF REVIEW

    Directory of Open Access Journals (Sweden)

    William P. Ebben

    2002-06-01

    Full Text Available The effectiveness of plyometric training is well supported by research. Complex training has gained popularity as a training strategy combining weight training and plyometric training. Anecdotal reports recommend training in this fashion in order to improve muscular power and athletic performance. Recently, several studies have examined complex training. Despite the fact that questions remain about the potential effectiveness and implementation of this type of training, results of recent studies are useful in guiding practitioners in the development and implementation of complex training programs. In some cases, research suggests that complex training has an acute ergogenic effect on upper body power and the results of acute and chronic complex training include improved jumping performance. Improved performance may require three to four minutes rest between the weight training and plyometrics sets and the use of heavy weight training loads

  3. Managing complexity insights, concepts, applications

    CERN Document Server

    Helbing, Dirk

    2007-01-01

    Each chapter in Managing Complexity focuses on analyzing real-world complex systems and transferring knowledge from the complex-systems sciences to applications in business, industry and society. The interdisciplinary contributions range from markets and production through logistics, traffic control, and critical infrastructures, up to network design, information systems, social conflicts and building consensus. They serve to raise readers' awareness concerning the often counter-intuitive behavior of complex systems and to help them integrate insights gained in complexity research into everyday planning, decision making, strategic optimization, and policy. Intended for a broad readership, the contributions have been kept largely non-technical and address a general, scientifically literate audience involved in corporate, academic, and public institutions.

  4. Complex systems in metabolic engineering.

    Science.gov (United States)

    Winkler, James D; Erickson, Keesha; Choudhury, Alaksh; Halweg-Edwards, Andrea L; Gill, Ryan T

    2015-12-01

    Metabolic engineers manipulate intricate biological networks to build efficient biological machines. The inherent complexity of this task, derived from the extensive and often unknown interconnectivity between and within these networks, often prevents researchers from achieving desired performance. Other fields have developed methods to tackle the issue of complexity for their unique subset of engineering problems, but to date, there has not been extensive and comprehensive examination of how metabolic engineers use existing tools to ameliorate this effect on their own research projects. In this review, we examine how complexity affects engineering at the protein, pathway, and genome levels within an organism, and the tools for handling these issues to achieve high-performing strain designs. Quantitative complexity metrics and their applications to metabolic engineering versus traditional engineering fields are also discussed. We conclude by predicting how metabolic engineering practices may advance in light of an explicit consideration of design complexity. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. European Conference on Complex Systems

    CERN Document Server

    Pellegrini, Francesco; Caldarelli, Guido; Merelli, Emanuela

    2016-01-01

    This work contains a stringent selection of extended contributions presented at the meeting of 2014 and its satellite meetings, reflecting scope, diversity and richness of research areas in the field, both fundamental and applied. The ECCS meeting, held under the patronage of the Complex Systems Society, is an annual event that has become the leading European conference devoted to complexity science. It offers cutting edge research and unique opportunities to study novel scientific approaches in a multitude of application areas. ECCS'14, its eleventh occurrence, took place in Lucca, Italy. It gathered some 650 scholars representing a wide range of topics relating to complex systems research, with emphasis on interdisciplinary approaches. The editors are among the best specialists in the area. The book is of great interest to scientists, researchers and graduate students in complexity, complex systems and networks.

  6. Innovation in a complex environment

    Directory of Open Access Journals (Sweden)

    René Pellissier

    2012-02-01

    Full Text Available Background: As our world becomes more global and competitive yet less predictable, the focus seems to be increasingly on looking to innovation activities to remain competitive. Although there is little doubt that a nation’s competitiveness is embedded in its innovativeness, the complex environment should not be ignored. Complexity is not accounted for in balance sheets or reported in reports; it becomes entrenched in every activity in the organisation. Innovation takes many forms and comes in different shapes.Objectives: The study objectives were, firstly, to establish the determinants for complexity and how these can be addressed from a design point of view in order to ensure innovation success and, secondly, to determine how this changes innovation forms and applications.Method: Two approaches were offered to deal with a complex environment – one allowing for complexity for organisational innovation and the other introducing reductionism to minimise complexity. These approaches were examined in a qualitative study involving case studies, open-ended interviews and content analysis between seven developing economy (South African organisations and seven developed economy (US organisations.Results: This study presented a proposed framework for (organisational innovation in a complex environment versus a framework that minimises complexity. The comparative organisational analysis demonstrated the importance of initiating organisational innovation to address internal and external complexity, with the focus being on the leadership actions, their selected operating models and resultant organisational innovations designs, rather than on technological innovations.Conclusion: This study cautioned the preference for technological innovation within organisations and suggested alternative innovation forms (such as organisational and management innovation be used to remain competitive in a complex environment. 

  7. The complexity of anatomical systems

    Directory of Open Access Journals (Sweden)

    Grizzi Fabio

    2005-07-01

    Full Text Available Abstract Background The conception of anatomical entities as a hierarchy of infinitely graduated forms and the increase in the number of observed anatomical sub-entities and structural variables has generated a growing complexity, thus highlighting new properties of organised biological matter. Results (1 Complexity is so pervasive in the anatomical world that it has come to be considered as a primary characteristic of anatomical systems. (2 Anatomical entities, when viewed at microscopic as well as macroscopic level of observation, show a different degree of complexity. (3 Complexity can reside in the structure of the anatomical system (having many diverse parts with varying interactions or an intricate architecture or in its behaviour. Often complexity in structure and behaviour go together. (4 Complex systems admit many descriptions (ways of looking at the system each of which is only partially true. Each way of looking at a complex system requires its own description, its own mode of analysis and its own breaking down of the system in different parts; (5 Almost all the anatomical entities display hierarchical forms: their component structures at different spatial scales or their process at different time scales are related to each other. Conclusion The need to find a new way of observing and measuring anatomical entities, and objectively quantifying their different structural changes, prompted us to investigate the non-Euclidean geometries and the theories of complexity, and to apply their concepts to human anatomy. This attempt has led us to reflect upon the complex significance of the shape of an observed anatomical entity. Its changes have been defined in relation to variations in its status: from a normal (i.e. natural to a pathological or altered state introducing the concepts of kinematics and dynamics of anatomical forms, speed of their changes, and that of scale of their observation.

  8. Management of complex dynamical systems

    Science.gov (United States)

    MacKay, R. S.

    2018-02-01

    Complex dynamical systems are systems with many interdependent components which evolve in time. One might wish to control their trajectories, but a more practical alternative is to control just their statistical behaviour. In many contexts this would be both sufficient and a more realistic goal, e.g. climate and socio-economic systems. I refer to it as ‘management’ of complex dynamical systems. In this paper, some mathematics for management of complex dynamical systems is developed in the weakly dependent regime, and questions are posed for the strongly dependent regime.

  9. Advances in computational complexity theory

    CERN Document Server

    Cai, Jin-Yi

    1993-01-01

    This collection of recent papers on computational complexity theory grew out of activities during a special year at DIMACS. With contributions by some of the leading experts in the field, this book is of lasting value in this fast-moving field, providing expositions not found elsewhere. Although aimed primarily at researchers in complexity theory and graduate students in mathematics or computer science, the book is accessible to anyone with an undergraduate education in mathematics or computer science. By touching on some of the major topics in complexity theory, this book sheds light on this burgeoning area of research.

  10. Scattering methods in complex fluids

    CERN Document Server

    Chen, Sow-Hsin

    2015-01-01

    Summarising recent research on the physics of complex liquids, this in-depth analysis examines the topic of complex liquids from a modern perspective, addressing experimental, computational and theoretical aspects of the field. Selecting only the most interesting contemporary developments in this rich field of research, the authors present multiple examples including aggregation, gel formation and glass transition, in systems undergoing percolation, at criticality, or in supercooled states. Connecting experiments and simulation with key theoretical principles, and covering numerous systems including micelles, micro-emulsions, biological systems, and cement pastes, this unique text is an invaluable resource for graduate students and researchers looking to explore and understand the expanding field of complex fluids.

  11. Complexing-precipitating geochemical barriers

    Science.gov (United States)

    Savenko, A. V.

    2017-02-01

    New types of geochemical barriers on which chemical elements are immobilized as a result of combined complex formation and precipitation of barely soluble mineral phases are examined. A significant concentration of major components (Fe, Al) forming more stable complexes than an immobilized component X in the material is a necessary condition for this type of geochemical barriers. Filtration of the solution through a geochemical barrier is accompanied by substitution of X in the complex with a major component. As a result, the activity of X in the free state increases, and one barely soluble mineral phase or another of the component X precipitates when the state of saturation is achieved.

  12. Complexity and Shock Wave Geometries

    OpenAIRE

    Stanford, Douglas; Susskind, Leonard

    2014-01-01

    In this paper we refine a conjecture relating the time-dependent size of an Einstein-Rosen bridge to the computational complexity of the of the dual quantum state. Our refinement states that the complexity is proportional to the spatial volume of the ERB. More precisely, up to an ambiguous numerical coefficient, we propose that the complexity is the regularized volume of the largest codimension one surface crossing the bridge, divided by $G_N l_{AdS}$. We test this conjecture against a wide v...

  13. Complexity in physics and technology

    CERN Document Server

    Garrido, Manuel S

    1992-01-01

    A system is loosely defined as complex if it is composed of a large number of elements, interacting with each other, and the emergent global dynamics is qualitatively different from the dynamics of each one of the parts. The global dynamics may be either ordered or chaotic and among the most interesting emergent global properties are those of learning and adaptation.Complex systems, in the above sense, appear in many fields ranging from physics and technology to life and social sciences. Research in complex systems involves therefore a wide range of topics, studied in seemingly disparate field

  14. Complex Topographic Feature Ontology Patterns

    Science.gov (United States)

    Varanka, Dalia E.; Jerris, Thomas J.

    2015-01-01

    Semantic ontologies are examined as effective data models for the representation of complex topographic feature types. Complex feature types are viewed as integrated relations between basic features for a basic purpose. In the context of topographic science, such component assemblages are supported by resource systems and found on the local landscape. Ontologies are organized within six thematic modules of a domain ontology called Topography that includes within its sphere basic feature types, resource systems, and landscape types. Context is constructed not only as a spatial and temporal setting, but a setting also based on environmental processes. Types of spatial relations that exist between components include location, generative processes, and description. An example is offered in a complex feature type ‘mine.’ The identification and extraction of complex feature types are an area for future research.

  15. FUZZY MATHEMATICS AND CUBICAL COMPLEXES

    Directory of Open Access Journals (Sweden)

    ADOLFO MACEDA MENDEZ

    2017-07-01

    applications in digital image processing and in the study of dynamical systems, but in the actual literature there is not an extension of their properties using fuzzy sets. In this paper is proposed a generalization of the concept of cubical complex and of some of their properties, such as connectedness, polyhedral realization, connected component and holes, using fuzzy sets. The upper and lower trees of a fuzzy cubical complex are defined, which give information about the way in which its regional extrema are related. The homology groups of a fuzzy cubical complex are defined and it is shown that the rank of the 0-homology group of a given level is equal with the number of regional maxima of that level. Finally, it is shown how to associate a fuzzy cubical complex with a bidimensional digital grayscale image in order to study somo of its topological properties.

  16. Association theories for complex thermodynamics

    DEFF Research Database (Denmark)

    Kontogeorgis, Georgios; Rafiqul Gani

    2013-01-01

    Thermodynamics of complex systems (e.g. with associating molecules, multicomponent mixtures, multiphase equilibria, wide ranges of conditions, estimation of many different properties simultaneously) is a topic of great importance in chemical engineering and for a wide range of industrial...... promising direction for a general and useful for engineering purposes modeling of complex thermodynamics is via the use of association theories e.g. those based on chemical theory (like APACT), or on the lattice theory (like NRHB) or those based on perturbation theory (like SAFT and CPA). The purpose...... applications. While specialized models can handle different cases, even complex ones, with the advent of powerful theories and computers there is the hope that a single or a few models could be suitable for a general modeling of complex thermodynamics. After more than 100 years with active use of thermodynamic...

  17. Liquid-crystalline lanthanide complexes

    OpenAIRE

    Binnemans, Koen

    2000-01-01

    The paper describes the recent developments in the field of liquid-crystalline lanthanide complexes. The role of trivalent lanthanide ions as the central metal ion in metallomesogens is considered. An outlook for the future is given.

  18. Fundamental Complexity Measures of Life

    CERN Document Server

    Grandpierre, Attila

    2012-01-01

    At present, there is a great deal of confusion regarding complexity and its measures (reviews on complexity measures are found in, e.g. Lloyd, 2001 and Shalizi, 2006 and more references therein). Moreover, there is also confusion regarding the nature of life. In this situation, it seems the task of determining the fundamental complexity measures of life is especially difficult. Yet this task is just part of a greater task: obtaining substantial insights into the nature of biological evolution. We think that without a firm quantitative basis characterizing the most fundamental aspects of life, it is impossible to overcome the confusion so as to clarify the nature of biological evolution. The approach we present here offers such quantitative measures of complexity characterizing biological organization and, as we will see, evolution.

  19. Complex systems: physics beyond physics

    CERN Document Server

    Holovatch, Yurij; Thurner, Stefan

    2016-01-01

    Complex systems are characterized by specific time-dependent interactions among their many constituents. As a consequence they often manifest rich, non-trivial and unexpected behavior. Examples arise both in the physical and non-physical world. The study of complex systems forms a new interdisciplinary research area that cuts across physics, biology, ecology, economics, sociology, and the humanities. In this paper we review the essence of complex systems from a physicist's point of view, and try to clarify what makes them conceptually different from systems that are traditionally studied in physics. Our goal is to demonstrate how the dynamics of such systems may be conceptualized in quantitative and predictive terms by extending notions from statistical physics and how they can often be captured in a framework of co-evolving multiplex network structures. We mention three areas of complex-systems science that are currently studied extensively, the science of cities, dynamics of societies, and the representatio...

  20. Cap-binding complex (CBC)

    National Research Council Canada - National Science Library

    Gonatopoulos-Pournatzis, Thomas; Cowling, Victoria H

    2014-01-01

    .... One of the most important mediators of 7mG functions is CBC (cap-binding complex). CBC has a key role in several gene expression mechanisms, including transcription, splicing, transcript export and translation...