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Sample records for binds flexible gc-rich

  1. Stabilization of Oncostatin-M mRNA by Binding of Nucleolin to a GC-Rich Element in Its 3'UTR.

    Science.gov (United States)

    Saha, Sucharita; Chakraborty, Alina; Bandyopadhyay, Sumita Sengupta

    2016-04-01

    Oncostatin-M (OSM) is a patho-physiologically important pleiotropic, multifunctional cytokine. OSM mRNA sequence analysis revealed that its 3'UTR contains three highly conserved GC-rich cis-elements (GCREs) whose role in mRNA stability is unidentified. In the present study, the functional role of the proximal GC-rich region of osm 3'-UTR (GCRE-1) in post-transcriptional regulation of osm expression in U937 cells was assessed by transfecting construct containing GCRE-1 at 3'-end of a fairly stable reporter gene followed by analysis of the expression of the reporter. GCRE-1 showed mRNA destabilizing activity; however, upon PMA treatment the reporter message containing GCRE-1 was stabilized. This stabilization is owing to a time-dependent progressive binding of trans-factors (at least five proteins) to GCRE-1 post-PMA treatment. Nucleolin was identified as one of the proteins in the RNP complex of GCRE-1 with PMA-treated U937 cytosolic extracts by oligo-dT affinity chromatography of poly-adenylated GCRE-1. Immuno-blot revealed time-dependent enhancement of nucleolin in the cytoplasm which in turn directly binds GCRE-1. RNA co-immunoprecipitation confirmed the GCRE-1-nucleolin interaction in vivo. To elucidate the functional role of nucleolin in stabilization of osm mRNA, nucleolin was overexpressed in U937 cells and found to stabilize the intrinsic osm mRNA, where co-transfection with the reporter containing GCRE-1 confirms the role of GCRE-1 in stabilization of the reporter mRNA. Thus, in conclusion, the results asserted that PMA treatment in U937 cells leads to cytoplasmic translocation of nucleolin that directly binds GCRE-1, one of the major GC-rich instability elements, thereby stabilizing the osm mRNA. PMID:26399567

  2. Genome-wide chromatin remodeling identified at GC-rich long nucleosome-free regions.

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    Karin Schwarzbauer

    Full Text Available To gain deeper insights into principles of cell biology, it is essential to understand how cells reorganize their genomes by chromatin remodeling. We analyzed chromatin remodeling on next generation sequencing data from resting and activated T cells to determine a whole-genome chromatin remodeling landscape. We consider chromatin remodeling in terms of nucleosome repositioning which can be observed most robustly in long nucleosome-free regions (LNFRs that are occupied by nucleosomes in another cell state. We found that LNFR sequences are either AT-rich or GC-rich, where nucleosome repositioning was observed much more prominently in GC-rich LNFRs - a considerable proportion of them outside promoter regions. Using support vector machines with string kernels, we identified a GC-rich DNA sequence pattern indicating loci of nucleosome repositioning in resting T cells. This pattern appears to be also typical for CpG islands. We found out that nucleosome repositioning in GC-rich LNFRs is indeed associated with CpG islands and with binding sites of the CpG-island-binding ZF-CXXC proteins KDM2A and CFP1. That this association occurs prominently inside and also prominently outside of promoter regions hints at a mechanism governing nucleosome repositioning that acts on a whole-genome scale.

  3. A Fundamental Study of the PCR Amplification of GC-Rich DNA Templates

    OpenAIRE

    Mammedov, TG.; Pienaar, E; Whitney, SE; TerMaat, JR.; Carvill, G.; Goliath, R; Subramanian, A.; Viljoen, HJ

    2008-01-01

    A theoretical analysis is presented with experimental confirmation to conclusively demonstrate the critical role that annealing plays in efficient PCR amplification of GC-rich templates. The analysis is focused on the annealing of primers at alternative binding sites (competitive annealing) and the main result is a quantitative expression of the efficiency (η) of annealing as a function of temperature (TA), annealing period tA) and template composition. The optimal efficiency lies in a narrow...

  4. A new RACE method for extremely GC-rich genes

    OpenAIRE

    Shi, Xianzong; Jarvis, Donald L.

    2006-01-01

    Rapid amplification of cDNA ends (RACE) is widely utilized to determine the 5′- and 3′-terminal nucleotide sequences of genes. Many different RACE methods have been developed to meet various requirements, but none address the difficult problems that arise when trying to isolate the ends of extremely GC-rich genes. In this study, we found that we were unable to isolate the correct 5′ or 3′ ends of an insect gene, which appeared to include extremely GC-rich sequences, using current RACE methods...

  5. GC-rich sequence elements recruit PRC2 in mammalian ES cells.

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    Eric M Mendenhall

    Full Text Available Polycomb proteins are epigenetic regulators that localize to developmental loci in the early embryo where they mediate lineage-specific gene repression. In Drosophila, these repressors are recruited to sequence elements by DNA binding proteins associated with Polycomb repressive complex 2 (PRC2. However, the sequences that recruit PRC2 in mammalian cells have remained obscure. To address this, we integrated a series of engineered bacterial artificial chromosomes into embryonic stem (ES cells and examined their chromatin. We found that a 44 kb region corresponding to the Zfpm2 locus initiates de novo recruitment of PRC2. We then pinpointed a CpG island within this locus as both necessary and sufficient for PRC2 recruitment. Based on this causal demonstration and prior genomic analyses, we hypothesized that large GC-rich elements depleted of activating transcription factor motifs mediate PRC2 recruitment in mammals. We validated this model in two ways. First, we showed that a constitutively active CpG island is able to recruit PRC2 after excision of a cluster of activating motifs. Second, we showed that two 1 kb sequence intervals from the Escherichia coli genome with GC-contents comparable to a mammalian CpG island are both capable of recruiting PRC2 when integrated into the ES cell genome. Our findings demonstrate a causal role for GC-rich sequences in PRC2 recruitment and implicate a specific subset of CpG islands depleted of activating motifs as instrumental for the initial localization of this key regulator in mammalian genomes.

  6. Molecular Cytogenetics in Trough Shells (Mactridae, Bivalvia: Divergent GC-Rich Heterochromatin Content

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    Daniel García-Souto

    2016-08-01

    Full Text Available The family Mactridae is composed of a diverse group of marine organisms, commonly known as trough shells or surf clams, which illustrate a global distribution. Although this family includes some of the most fished and cultured bivalve species, their chromosomes are poorly studied. In this work, we analyzed the chromosomes of Spisula solida, Spisula subtruncata and Mactra stultorum by means of fluorochrome staining, C-banding and fluorescent in situ hybridization using 28S ribosomal DNA (rDNA, 5S rDNA, H3 histone gene and telomeric probes. All three trough shells presented 2n = 38 chromosomes but different karyotype compositions. As happens in most bivalves, GC-rich regions were limited to the nucleolus organizing regions in Spisula solida. In contrast, many GC-rich heterochromatic bands were detected in both Spisula subtruncata and Mactra stultorum. Although the three trough shells presented single 5S rDNA and H3 histone gene clusters, their chromosomal locations differed. Regarding major rDNA clusters, while Spisula subtruncata presented a single cluster, both Spisula solida and Mactra stultorum showed two. No evidence of intercalary telomeric signals was detected in these species. The molecular cytogenetic characterization of these taxa will contribute to understanding the role played by chromosome changes in the evolution of trough shells.

  7. Molecular Cytogenetics in Trough Shells (Mactridae, Bivalvia): Divergent GC-Rich Heterochromatin Content.

    Science.gov (United States)

    García-Souto, Daniel; Pérez-García, Concepción; Kendall, Jack; Pasantes, Juan J

    2016-01-01

    The family Mactridae is composed of a diverse group of marine organisms, commonly known as trough shells or surf clams, which illustrate a global distribution. Although this family includes some of the most fished and cultured bivalve species, their chromosomes are poorly studied. In this work, we analyzed the chromosomes of Spisula solida, Spisula subtruncata and Mactra stultorum by means of fluorochrome staining, C-banding and fluorescent in situ hybridization using 28S ribosomal DNA (rDNA), 5S rDNA, H3 histone gene and telomeric probes. All three trough shells presented 2n = 38 chromosomes but different karyotype compositions. As happens in most bivalves, GC-rich regions were limited to the nucleolus organizing regions in Spisula solida. In contrast, many GC-rich heterochromatic bands were detected in both Spisula subtruncata and Mactra stultorum. Although the three trough shells presented single 5S rDNA and H3 histone gene clusters, their chromosomal locations differed. Regarding major rDNA clusters, while Spisula subtruncata presented a single cluster, both Spisula solida and Mactra stultorum showed two. No evidence of intercalary telomeric signals was detected in these species. The molecular cytogenetic characterization of these taxa will contribute to understanding the role played by chromosome changes in the evolution of trough shells. PMID:27537915

  8. GC-Rich Extracellular DNA Induces Oxidative Stress, Double-Strand DNA Breaks, and DNA Damage Response in Human Adipose-Derived Mesenchymal Stem Cells

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    Svetlana Kostyuk

    2015-01-01

    Full Text Available Background. Cell free DNA (cfDNA circulates throughout the bloodstream of both healthy people and patients with various diseases. CfDNA is substantially enriched in its GC-content as compared with human genomic DNA. Principal Findings. Exposure of haMSCs to GC-DNA induces short-term oxidative stress (determined with H2DCFH-DA and results in both single- and double-strand DNA breaks (comet assay and γH2AX, foci. As a result in the cells significantly increases the expression of repair genes (BRCA1 (RT-PCR, PCNA (FACS and antiapoptotic genes (BCL2 (RT-PCR and FACS, BCL2A1, BCL2L1, BIRC3, and BIRC2 (RT-PCR. Under the action of GC-DNA the potential of mitochondria was increased. Here we show that GC-rich extracellular DNA stimulates adipocyte differentiation of human adipose-derived mesenchymal stem cells (haMSCs. Exposure to GC-DNA leads to an increase in the level of RNAPPARG2 and LPL (RT-PCR, in the level of fatty acid binding protein FABP4 (FACS analysis and in the level of fat (Oil Red O. Conclusions. GC-rich fragments in the pool of cfDNA can potentially induce oxidative stress and DNA damage response and affect the direction of mesenchymal stem cells differentiation in human adipose—derived mesenchymal stem cells. Such a response may be one of the causes of obesity or osteoporosis.

  9. Human CST Facilitates Genome-wide RAD51 Recruitment to GC-Rich Repetitive Sequences in Response to Replication Stress.

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    Chastain, Megan; Zhou, Qing; Shiva, Olga; Whitmore, Leanne; Jia, Pingping; Dai, Xueyu; Huang, Chenhui; Fadri-Moskwik, Maria; Ye, Ping; Chai, Weihang

    2016-08-01

    The telomeric CTC1/STN1/TEN1 (CST) complex has been implicated in promoting replication recovery under replication stress at genomic regions, yet its precise role is unclear. Here, we report that STN1 is enriched at GC-rich repetitive sequences genome-wide in response to hydroxyurea (HU)-induced replication stress. STN1 deficiency exacerbates the fragility of these sequences under replication stress, resulting in chromosome fragmentation. We find that upon fork stalling, CST proteins form distinct nuclear foci that colocalize with RAD51. Furthermore, replication stress induces physical association of CST with RAD51 in an ATR-dependent manner. Strikingly, CST deficiency diminishes HU-induced RAD51 foci formation and reduces RAD51 recruitment to telomeres and non-telomeric GC-rich fragile sequences. Collectively, our findings establish that CST promotes RAD51 recruitment to GC-rich repetitive sequences in response to replication stress to facilitate replication restart, thereby providing insights into the mechanism underlying genome stability maintenance.

  10. Perturbation Approaches for Exploring Protein Binding Site Flexibility to Predict Transient Binding Pockets.

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    Kokh, Daria B; Czodrowski, Paul; Rippmann, Friedrich; Wade, Rebecca C

    2016-08-01

    Simulations of the long-time scale motions of a ligand binding pocket in a protein may open up new perspectives for the design of compounds with steric or chemical properties differing from those of known binders. However, slow motions of proteins are difficult to access using standard molecular dynamics (MD) simulations and are thus usually neglected in computational drug design. Here, we introduce two nonequilibrium MD approaches to identify conformational changes of a binding site and detect transient pockets associated with these motions. The methods proposed are based on the rotamerically induced perturbation (RIP) MD approach, which employs perturbation of side-chain torsional motion for initiating large-scale protein movement. The first approach, Langevin-RIP (L-RIP), entails a series of short Langevin MD simulations, each starting with perturbation of one of the side-chains lining the binding site of interest. L-RIP provides extensive sampling of conformational changes of the binding site. In less than 1 ns of MD simulation with L-RIP, we observed distortions of the α-helix in the ATP binding site of HSP90 and flipping of the DFG loop in Src kinase. In the second approach, RIPlig, a perturbation is applied to a pseudoligand placed in different parts of a binding pocket, which enables flexible regions of the binding site to be identified in a small number of 10 ps MD simulations. The methods were evaluated for four test proteins displaying different types and degrees of binding site flexibility. Both methods reveal all transient pocket regions in less than a total of 10 ns of simulations, even though many of these regions remained closed in 100 ns conventional MD. The proposed methods provide computationally efficient tools to explore binding site flexibility and can aid in the functional characterization of protein pockets, and the identification of transient pockets for ligand design. PMID:27399277

  11. Complete Genome Sequence of Elephant Endotheliotropic Herpesvirus 4, the First Example of a GC-Rich Branch Proboscivirus.

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    Ling, Paul D; Long, Simon Y; Fuery, Angela; Peng, Rong-Sheng; Heaggans, Sarah Y; Qin, Xiang; Worley, Kim C; Dugan, Shannon; Hayward, Gary S

    2016-01-01

    A novel group of mammalian DNA viruses called elephant endotheliotropic herpesviruses (EEHVs) belonging to the Proboscivirus genus has been associated with nearly 100 cases of highly lethal acute hemorrhagic disease in young Asian elephants worldwide. The complete 180-kb genomes of prototype strains from three AT-rich branch viruses, EEHV1A, EEHV1B, and EEHV5, have been published. However, less than 6 kb of DNA sequence each from EEHV3, EEHV4, and EEHV7 showed them to be a hugely diverged second major branch with GC-rich characteristics. Here, we determined the complete 206-kb genome of EEHV4(Baylor) directly from trunk wash DNA by next-generation sequencing and de novo assembly procedures. Among a total of 119 genes with an overall colinear organization similar to those of the AT-rich EEHVs, major features of EEHV4 include a family of 26 paralogous 7xTM and vGPCR-like genes plus 25 novel or missing genes. The genome also contains an unusual distribution of tracts of 5 to 11 successive A or T nucleotides in intergenic domains between the mostly much higher GC content protein coding regions. Furthermore, an extremely high GC-rich bias in the third wobble position of codons clearly delineates the coding regions for many but not all proteins. There are also two novel captured cellular genes, including a C-type lectin (vECTL) and an O-linked acetylglucosamine transferase (vOGT), as well as an unusually large and complex Ori-Lyt dyad symmetry domain. Finally, 30 kb from a second strain proved to include three small chimeric domains, indicating the existence of distinct EEHV4A and EEHV4B subtypes. IMPORTANCE Multiple species of herpesviruses from three different lineages of the Proboscivirus genus (EEHV1/6, EEHV2/5, and EEHV3/4/7) infect both Asian and African elephants, but lethal hemorrhagic disease is largely confined to Asian elephant calves and is predominantly associated with EEHV1. Milder disease caused by EEHV5 or EEHV4 is being increasingly recognized as well

  12. The GC-Rich Mitochondrial and Plastid Genomes of the Green Alga Coccomyxa Give Insight into the Evolution of Organelle DNA Nucleotide Landscape

    Energy Technology Data Exchange (ETDEWEB)

    Smith, David Roy; Burki, Fabien; Yamada, Takashi; Grimwood, Jane; Grigoriev, Igor V.; Van Etten, James L.; Keeling, Patrick J.

    2011-05-13

    Most of the available mitochondrial and plastid genome sequences are biased towards adenine and thymine (AT) over guanine and cytosine (GC). Examples of GC-rich organelle DNAs are limited to a small but eclectic list of species, including certain green algae. Here, to gain insight in the evolution of organelle nucleotide landscape, we present the GC-rich mitochondrial and plastid DNAs from the trebouxiophyte green alga Coccomyxa sp. C-169. We compare these sequences with other GC-rich organelle DNAs and argue that the forces biasing them towards G and C are nonadaptive and linked to the metabolic and/or life history features of this species. The Coccomyxa organelle genomes are also used for phylogenetic analyses, which highlight the complexities in trying to resolve the interrelationships among the core chlorophyte green algae, but ultimately favour a sister relationship between the Ulvophyceae and Chlorophyceae, with the Trebouxiophyceae branching at the base of the chlorophyte crown.

  13. Efficient Translation Initiation Directed by the 900-Nucleotide-Long and GC-Rich 5′ Untranslated Region of the Human Retrotransposon LINE-1 mRNA Is Strictly Cap Dependent Rather than Internal Ribosome Entry Site Mediated▿

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    Dmitriev, Sergey E.; Andreev, Dmitri E.; Terenin, Ilya M.; Olovnikov, Ivan A.; Prassolov, Vladimir S.; Merrick, William C.; Shatsky, Ivan N.

    2007-01-01

    Retrotransposon L1 is a mobile genetic element of the LINE family that is extremely widespread in the mammalian genome. It encodes a dicistronic mRNA, which is exceptionally rare among eukaryotic cellular mRNAs. The extremely long and GC-rich L1 5′ untranslated region (5′UTR) directs synthesis of numerous copies of RNA-binding protein ORF1p per mRNA. One could suggest that the 5′UTR of L1 mRNA contained a powerful internal ribosome entry site (IRES) element. Using transfection of cultured cells with the polyadenylated monocistronic (L1 5′UTR-Fluc) or bicistronic (Rluc-L1 5′UTR-Fluc) RNA constructs, capped or uncapped, it has been firmly established that the 5′UTR of L1 does not contain an IRES. Uncapping reduces the initiation activity of the L1 5′UTR to that of background. Moreover, the translation is inhibited by upstream AUG codons in the 5′UTR. Nevertheless, this cap-dependent initiation activity of the L1 5′UTR was unexpectedly high and resembles that of the beta-actin 5′UTR (84 nucleotides long). Strikingly, the deletion of up to 80% of the nucleotide sequence of the L1 5′UTR, with most of its stem loops, does not significantly change its translation initiation efficiency. These data can modify current ideas on mechanisms used by 40S ribosomal subunits to cope with complex 5′UTRs and call into question the conception that every long GC-rich 5′UTR working with a high efficiency has to contain an IRES. Our data also demonstrate that the ORF2 translation initiation is not directed by internal initiation, either. It is very inefficient and presumably based on a reinitiation event. PMID:17470553

  14. Efficient translation initiation directed by the 900-nucleotide-long and GC-rich 5' untranslated region of the human retrotransposon LINE-1 mRNA is strictly cap dependent rather than internal ribosome entry site mediated.

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    Dmitriev, Sergey E; Andreev, Dmitri E; Terenin, Ilya M; Olovnikov, Ivan A; Prassolov, Vladimir S; Merrick, William C; Shatsky, Ivan N

    2007-07-01

    Retrotransposon L1 is a mobile genetic element of the LINE family that is extremely widespread in the mammalian genome. It encodes a dicistronic mRNA, which is exceptionally rare among eukaryotic cellular mRNAs. The extremely long and GC-rich L1 5' untranslated region (5'UTR) directs synthesis of numerous copies of RNA-binding protein ORF1p per mRNA. One could suggest that the 5'UTR of L1 mRNA contained a powerful internal ribosome entry site (IRES) element. Using transfection of cultured cells with the polyadenylated monocistronic (L1 5'UTR-Fluc) or bicistronic (Rluc-L1 5'UTR-Fluc) RNA constructs, capped or uncapped, it has been firmly established that the 5'UTR of L1 does not contain an IRES. Uncapping reduces the initiation activity of the L1 5'UTR to that of background. Moreover, the translation is inhibited by upstream AUG codons in the 5'UTR. Nevertheless, this cap-dependent initiation activity of the L1 5'UTR was unexpectedly high and resembles that of the beta-actin 5'UTR (84 nucleotides long). Strikingly, the deletion of up to 80% of the nucleotide sequence of the L1 5'UTR, with most of its stem loops, does not significantly change its translation initiation efficiency. These data can modify current ideas on mechanisms used by 40S ribosomal subunits to cope with complex 5'UTRs and call into question the conception that every long GC-rich 5'UTR working with a high efficiency has to contain an IRES. Our data also demonstrate that the ORF2 translation initiation is not directed by internal initiation, either. It is very inefficient and presumably based on a reinitiation event.

  15. Flexibility of PCNA-protein interface accommodates differential binding partners.

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    Anthony M Pedley

    Full Text Available The expanding roles of PCNA in functional assembly of DNA replication and repair complexes motivated investigation of the structural and dynamic properties guiding specificity of PCNA-protein interactions. A series of biochemical and computational analyses were combined to evaluate the PIP Box recognition features impacting complex formation. The results indicate subtle differences in topological and molecular descriptors distinguishing both affinity and stoichiometry of binding among PCNA-peptide complexes through cooperative effects. These features were validated using peptide mimics of p85α and Akt, two previously unreported PCNA binding partners. This study characterizes for the first time a reverse PIP Box interaction with PCNA. Small molecule ligand binding at the PIP Box interaction site confirmed the adaptive nature of the protein in dictating overall shape and implicates allosterism in transmitting biological effects.

  16. Influence of length and flexibility of spacers on the binding affinity of divalent ligands

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    Susanne Liese

    2015-05-01

    Full Text Available We present a quantitative model for the binding of divalent ligand–receptor systems. We study the influence of length and flexibility of the spacers on the overall binding affinity and derive general rules for the optimal ligand design. To this end, we first compare different polymeric models and determine the probability to simultaneously bind to two neighboring receptor binding pockets. In a second step the binding affinity of divalent ligands in terms of the IC50 value is derived. We find that a divalent ligand has the potential to bind more efficiently than its monovalent counterpart only, if the monovalent dissociation constant is lower than a critical value. This critical monovalent dissociation constant depends on the ligand-spacer length and flexibility as well as on the size of the receptor. Regarding the optimal ligand-spacer length and flexibility, we find that the average spacer length should be equal or slightly smaller than the distance between the receptor binding pockets and that the end-to-end spacer length fluctuations should be in the same range as the size of a receptor binding pocket.

  17. Influence of length and flexibility of spacers on the binding affinity of divalent ligands.

    Science.gov (United States)

    Liese, Susanne; Netz, Roland R

    2015-01-01

    We present a quantitative model for the binding of divalent ligand-receptor systems. We study the influence of length and flexibility of the spacers on the overall binding affinity and derive general rules for the optimal ligand design. To this end, we first compare different polymeric models and determine the probability to simultaneously bind to two neighboring receptor binding pockets. In a second step the binding affinity of divalent ligands in terms of the IC50 value is derived. We find that a divalent ligand has the potential to bind more efficiently than its monovalent counterpart only, if the monovalent dissociation constant is lower than a critical value. This critical monovalent dissociation constant depends on the ligand-spacer length and flexibility as well as on the size of the receptor. Regarding the optimal ligand-spacer length and flexibility, we find that the average spacer length should be equal or slightly smaller than the distance between the receptor binding pockets and that the end-to-end spacer length fluctuations should be in the same range as the size of a receptor binding pocket.

  18. Comparison of the Gene Coding Contents and Other Unusual Features of the GC-Rich and AT-Rich Branch Probosciviruses.

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    Ling, Paul D; Long, Simon Y; Zong, Jian-Chao; Heaggans, Sarah Y; Qin, Xiang; Hayward, Gary S

    2016-01-01

    Nearly 100 cases of lethal acute hemorrhagic disease in young Asian elephants have been reported worldwide. All tested cases contained high levels of elephant endotheliotropic herpesvirus (EEHV) DNA in pathological blood or tissue samples. Seven known major types of EEHVs have been partially characterized and shown to all belong to the novel Proboscivirus genus. However, the recently determined 206-kb EEHV4 genome proved to represent the prototype of a GC-rich branch virus that is very distinct from the previously published 180-kb EEHV1A, EEHV1B, and EEHV5A genomes, which all fall within an alternative AT-rich branch. Although EEHV4 retains the large family of 7xTM and vGPCR-like genes, six are unique to either just one or the other branch. While both branches display a highly enriched distribution of A and T tracts in intergenic domains, they are generally much larger within the GC-rich branch. Both branches retain the vGCNT1 acetylglucosamine transferase and at least one vOX-2 gene, but the two branches differ by 25 genes overall, with the AT-rich branch encoding a fucosyl transferase (vFUT9) plus two or three more vOX2 proteins and an immunoglobulin-like gene family that are all absent from the GC-rich branch. Several envelope glycoproteins retain only 15 to 20% protein identity or less across the two branches. Finally, the two plausible predicted transcriptional regulatory proteins display no homology at all to those in the alpha-, beta-, or gammaherpesvirus subfamilies. These results reinforce our previous proposal that the probosciviruses should be designated a new subfamily of mammalian herpesviruses. IMPORTANCE Multiple species of herpesviruses from three different lineages of the Proboscivirus genus (EEHV1/6, EEHV2/5, and EEHV3/4/7) infect either Asian or African elephants, but the highly lethal hemorrhagic disease is largely confined to Asian elephant calves and is predominantly associated with EEHV1. In the accompanying paper [P. D. Ling et al., m

  19. Ultrafast differential flexibility of Cro-protein binding domains of two operator DNAs with different sequences.

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    Choudhury, Susobhan; Ghosh, Basusree; Singh, Priya; Ghosh, Raka; Roy, Siddhartha; Pal, Samir Kumar

    2016-07-21

    The nature of the interface of specific protein-DNA complexes has attracted immense interest in contemporary molecular biology. Although extensive studies on the role of flexibility of DNA in the specific interaction in the genetic regulatory activity of lambda Cro (Cro-protein) have been performed, the exploration of quantitative features remains deficient. In this study, we have mutated (site directed mutagenesis: SDM) Cro-protein at the 37th position with a cysteine residue (G37C) retaining the functional integrity of the protein and labelled the cysteine residue, which is close to the interface, with a fluorescent probe (AEDANS), for the investigation of its interface with operator DNAs (OR3 and OR2). We have employed picosecond resolved polarization gated fluorescence spectroscopy and the well known strategy of solvation dynamics for the exploration of physical motions of the fluorescent probes and associated environments, respectively. Even though this particular probe on the protein (AEDANS) shows marginal changes in its structural flexibility upon interaction with the DNAs, a non-covalent DNA bound probe (DAPI), which binds to the minor groove, shows a major differential alteration in the dynamical flexibility in the OR3-Cro complex when compared to that of the OR2 complex with the Cro-protein. We attempt to correlate the observed significant structural fluctuation of the Cro-protein binding domain of OR3 for the specificity of the protein to the operator DNA. PMID:27326896

  20. Structural, vibrational, NMR, quantum chemical, DNA binding and protein docking studies of two flexible imine oximes

    Indian Academy of Sciences (India)

    YUNUS KAYA

    2016-09-01

    Two flexible imine oxime molecules, namely, 3-(pyridin-2-ylmethylimino)-butan-2-one oxime (HL¹) and 3-(pyridin-2-ylmethylimino)-pentan-2-one oxime (HL²) have been synthesized and characterized by elemental analysis, IR and NMR techniques. The conformational behavior was investigated using the density functional theory (DFT) with the B3LYP method combined with the 6-311++G(d,p) basis set. As a result of the conformational studies, three stable molecules and the most stable conformer were determined for the both imine oximes. The spectroscopic properties such as vibrational and NMR were calculated for the most stable conformer of the HL¹ and HL². The calculation results were applied to simulate infrared spectra of the title compounds, which show good agreement with observed spectra. In addition, the stable three molecules of the both imine oximes have been used to carry out DNA binding and protein docking studies with DNA and protein structures (downloaded from Protein Data Bank) using Discovery Studio 3.5 to find the most preferred binding mode of the ligands inside the DNA and protein cavity.

  1. β-lactoglobulin's conformational requirements for ligand binding at the calyx and the dimer interphase: a flexible docking study.

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    Lenin Domínguez-Ramírez

    Full Text Available β-lactoglobulin (BLG is an abundant milk protein relevant for industry and biotechnology, due significantly to its ability to bind a wide range of polar and apolar ligands. While hydrophobic ligand sites are known, sites for hydrophilic ligands such as the prevalent milk sugar, lactose, remain undetermined. Through the use of molecular docking we first, analyzed the known fatty acid binding sites in order to dissect their atomistic determinants and second, predicted the interaction sites for lactose with monomeric and dimeric BLG. We validated our approach against BLG structures co-crystallized with ligands and report a computational setup with a reduced number of flexible residues that is able to reproduce experimental results with high precision. Blind dockings with and without flexible side chains on BLG showed that: i 13 experimentally-determined ligands fit the calyx requiring minimal movement of up to 7 residues out of the 23 that constitute this binding site. ii Lactose does not bind the calyx despite conformational flexibility, but binds the dimer interface and an alternate Site C. iii Results point to a probable lactolation site in the BLG dimer interface, at K141, consistent with previous biochemical findings. In contrast, no accessible lysines are found near Site C. iv lactose forms hydrogen bonds with residues from both monomers stabilizing the dimer through a claw-like structure. Overall, these results improve our understanding of BLG's binding sites, importantly narrowing down the calyx residues that control ligand binding. Moreover, our results emphasize the importance of the dimer interface as an insufficiently explored, biologically relevant binding site of particular importance for hydrophilic ligands. Furthermore our analyses suggest that BLG is a robust scaffold for multiple ligand-binding, suitable for protein design, and advance our molecular understanding of its ligand sites to a point that allows manipulation to control

  2. Crystal structure of the S. solfataricus archaeal exosome reveals conformational flexibility in the RNA-binding ring.

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    Changrui Lu

    Full Text Available BACKGROUND: The exosome complex is an essential RNA 3'-end processing and degradation machinery. In archaeal organisms, the exosome consists of a catalytic ring and an RNA-binding ring, both of which were previously reported to assume three-fold symmetry. METHODOLOGY/PRINCIPAL FINDINGS: Here we report an asymmetric 2.9 A Sulfolobus solfataricus archaeal exosome structure in which the three-fold symmetry is broken due to combined rigid body and thermal motions mainly within the RNA-binding ring. Since increased conformational flexibility was also observed in the RNA-binding ring of the related bacterial PNPase, we speculate that this may reflect an evolutionarily conserved mechanism to accommodate diverse RNA substrates for degradation. CONCLUSION/SIGNIFICANCE: This study clearly shows the dynamic structures within the RNA-binding domains, which provides additional insights on mechanism of asymmetric RNA binding and processing.

  3. The four Zn fingers of MBNL1 provide a flexible platform for recognition of its RNA binding elements

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    Gates Devika P

    2011-05-01

    Full Text Available Abstract Background Muscleblind-like 1 (MBNL1 is an alternative splicing factor containing four CCCH Zinc fingers (ZnFs. The sequestration of MBNL1 by expanded CUG and CCUG repeats is a major component in causing myotonic dystrophy. In addition to binding the structured expanded CUG and CCUG repeats; previous results suggested that MBNL1 binds single-stranded RNAs containing GC dinucleotides. Results We performed a systematic analysis of MBNL1 binding to single-stranded RNAs. These studies revealed that a single GC dinucleotide in poly-uridine is sufficient for MBNL1 binding and that a second GC dinucleotide confers higher affinity MBNL1 binding. However additional GC dinucleotides do not enhance RNA binding. We also showed that the RNA sequences adjacent to the GC dinucleotides play an important role in MBNL1 binding with the following preference: uridines >cytidines >adenosines >guanosines. For high affinity binding by MBNL1, the distance between the two GC dinucleotides can vary from 1 to 17 nucleotides. Conclusions These results suggest that MBNL1 is highly flexible and able to adopt different conformations to recognize RNAs with varying sequence configurations. Although MBNL1 contains four ZnFs, only two ZnF - GC dinucleotide interactions are necessary for high affinity binding.

  4. Computational approaches to modeling receptor flexibility upon ligand binding: Application to interfacially activated enzymes

    DEFF Research Database (Denmark)

    Wade, R.C.; Sobolev, V.; Ortiz, A.R. .;

    1998-01-01

    Receptors generally undergo conformational change upon ligand binding. We describe how fairly simple techniques may be used in docking and design studies to account for some of the changes in the conformations of proteins on ligand binding. Simulations of protein-ligand interactions that give...... a more complete description of the dynamics important for ligand binding are then discussed. These methods are illustrated for phospholipase A(2) and lipase, enzymes that both undergo interfacial activation....

  5. The Fundamental Role of Flexibility on the Strength of Molecular Binding

    OpenAIRE

    Forrey, Christopher; Douglas, Jack F.; Gilson, Michael K.

    2012-01-01

    Non-covalent molecular association underlies a diverse set of biologically and technologically relevant phenomena, including the action of drugs on their biomolecular targets and self- and supra-molecular assembly processes. Computer models employed to model binding frequently use interaction potentials with atomistic detail while neglecting the thermal molecular motions of the binding species. However, errors introduced by this simplification and, more broadly, the thermodynamic consequences...

  6. Stabilizing a flexible interdomain hinge region harboring the SMB binding site drives uPAR into its closed conformation.

    Science.gov (United States)

    Zhao, Baoyu; Gandhi, Sonu; Yuan, Cai; Luo, Zhipu; Li, Rui; Gårdsvoll, Henrik; de Lorenzi, Valentina; Sidenius, Nicolai; Huang, Mingdong; Ploug, Michael

    2015-03-27

    The urokinase-type plasminogen activator receptor (uPAR) is a multidomain glycolipid-anchored membrane protein, which facilitates extracellular matrix remodeling by focalizing plasminogen activation to cell surfaces via its high-affinity interaction with uPA. The modular assembly of its three LU (Ly6/uPAR-like) domains is inherently flexible and binding of uPA drives uPAR into its closed conformation, which presents the higher-affinity state for vitronectin thus providing an allosteric regulatory mechanism. Using a new class of epitope-mapped anti-uPAR monoclonal antibodies (mAbs), we now demonstrate that the reciprocal stabilization is indeed also possible. By surface plasmon resonance studies, we show that these mAbs and vitronectin have overlapping binding sites on uPAR and that they share Arg91 as hotspot residue in their binding interfaces. The crystal structure solved for one of these uPAR·mAb complexes at 3.0Å clearly shows that this mAb preselects the closed uPAR conformation with an empty but correctly assembled large hydrophobic binding cavity for uPA. Accordingly, these mAbs inhibit the uPAR-dependent lamellipodia formation and migration on vitronectin-coated matrices irrespective of the conformational status of uPAR and its occupancy with uPA. This is the first study to the best of our knowledge, showing that the dynamic assembly of the three LU domains in uPARwt can be driven toward the closed form by an external ligand, which is not engaging the hydrophobic uPA binding cavity. As this binding interface is also exploited by the somatomedin B domain of vitronectin, therefore, this relationship should be taken into consideration when exploring uPAR-dependent cell adhesion and migration in vitronectin-rich environments. PMID:25659907

  7. Hydrogen/Deuterium Exchange Mass Spectrometry Reveals Specific Changes in the Local Flexibility of Plasminogen Activator Inhibitor 1 upon Binding to the Somatomedin B Domain of Vitronectin

    DEFF Research Database (Denmark)

    Trelle, Morten Beck; Hirschberg, Daniel; Jansson, Anna;

    2012-01-01

    and increases the thermal stability of the protein dramatically. We have used hydrogen/deuterium exchange mass spectrometry to assess the inherent structural flexibility of PAI-1 and to monitor the changes induced by SMB binding. Our data show that the PAI-1 core consisting of β-sheet B is rather protected...... against exchange with the solvent, while the remainder of the molecule is more dynamic. SMB binding causes a pronounced and widespread stabilization of PAI-1 that is not confined to the binding interface with SMB. We further explored the local structural flexibility in a mutationally stabilized PAI-1...

  8. Synthesis of Diphenyl Pyridazinone-based flexible system for conformational studies through weak noncovalent interactions: Application in DNA binding

    Indian Academy of Sciences (India)

    Ranjeet Kumar; Praveen Singh; Archana Gaurav; Pratima Yadav; Ranjana S Khanna; Ashish Kumar Tewari

    2016-04-01

    This paper reports conformational studies of pyridazinone-based flexible dimer connected through diethylamine linker. The conformational studies have been done by X-ray crystal structure and DFT calculation. Further, after crystallization, the compound has shown two types of crystals, one is hydrated and another one is non-hydrated. The hydrated and non-hydrated crystals showed difference in their conformation due to the presence of water in crystal lattice of hydrated crystal. The difference in their conformation has been proved by crystallographic studies, DSC curves and detailed analysis of Hirshfeld surfaces and fingerprint plots facilitating a comparison of intermolecular interactions. Along with conformational studies, this compound also showed DNA binding, as revealed in docking simulation studies.

  9. Crystal structure and conformational flexibility of the unligated FK506-binding protein FKBP12.6

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Hui; Mustafi, Sourajit M. [New York State Department of Health, Empire State Plaza, Albany, NY 12201 (United States); LeMaster, David M. [New York State Department of Health, Empire State Plaza, Albany, NY 12201 (United States); University at Albany – SUNY, Empire State Plaza, Albany, NY 12201 (United States); Li, Zhong [New York State Department of Health, Empire State Plaza, Albany, NY 12201 (United States); Héroux, Annie [Brookhaven National Laboratory, Upton, NY 11973 (United States); Li, Hongmin; Hernández, Griselda, E-mail: griselda@wadsworth.org [New York State Department of Health, Empire State Plaza, Albany, NY 12201 (United States); University at Albany – SUNY, Empire State Plaza, Albany, NY 12201 (United States)

    2014-03-01

    Two crystal forms of unligated FKBP12.6 exhibit multiple conformations in the active site and in the 80s loop, the primary site for known protein-recognition interactions. The previously unreported NMR backbone assignment of FKBP12.6 revealed extensive doubling of amide resonances, which reflects a slow conformational transition centered in the 80s loop. The primary known physiological function of FKBP12.6 involves its role in regulating the RyR2 isoform of ryanodine receptor Ca{sup 2+} channels in cardiac muscle, pancreatic β islets and the central nervous system. With only a single previously reported X-ray structure of FKBP12.6, bound to the immunosuppressant rapamycin, structural inferences for this protein have been drawn from the more extensive studies of the homologous FKBP12. X-ray structures at 1.70 and 1.90 Å resolution from P2{sub 1} and P3{sub 1}21 crystal forms are reported for an unligated cysteine-free variant of FKBP12.6 which exhibit a notable diversity of conformations. In one monomer from the P3{sub 1}21 crystal form, the aromatic ring of Phe59 at the base of the active site is rotated perpendicular to its typical orientation, generating a steric conflict for the immunosuppressant-binding mode. The peptide unit linking Gly89 and Val90 at the tip of the protein-recognition ‘80s loop’ is flipped in the P2{sub 1} crystal form. Unlike the >30 reported FKBP12 structures, the backbone conformation of this loop closely follows that of the first FKBP domain of FKBP51. The NMR resonances for 21 backbone amides of FKBP12.6 are doubled, corresponding to a slow conformational transition centered near the tip of the 80s loop, as recently reported for 31 amides of FKBP12. The comparative absence of doubling for residues along the opposite face of the active-site pocket in FKBP12.6 may in part reflect attenuated structural coupling owing to increased conformational plasticity around the Phe59 ring.

  10. Crystal structure and conformational flexibility of the unligated FK506-binding protein FKBP12.6

    International Nuclear Information System (INIS)

    Two crystal forms of unligated FKBP12.6 exhibit multiple conformations in the active site and in the 80s loop, the primary site for known protein-recognition interactions. The previously unreported NMR backbone assignment of FKBP12.6 revealed extensive doubling of amide resonances, which reflects a slow conformational transition centered in the 80s loop. The primary known physiological function of FKBP12.6 involves its role in regulating the RyR2 isoform of ryanodine receptor Ca2+ channels in cardiac muscle, pancreatic β islets and the central nervous system. With only a single previously reported X-ray structure of FKBP12.6, bound to the immunosuppressant rapamycin, structural inferences for this protein have been drawn from the more extensive studies of the homologous FKBP12. X-ray structures at 1.70 and 1.90 Å resolution from P21 and P3121 crystal forms are reported for an unligated cysteine-free variant of FKBP12.6 which exhibit a notable diversity of conformations. In one monomer from the P3121 crystal form, the aromatic ring of Phe59 at the base of the active site is rotated perpendicular to its typical orientation, generating a steric conflict for the immunosuppressant-binding mode. The peptide unit linking Gly89 and Val90 at the tip of the protein-recognition ‘80s loop’ is flipped in the P21 crystal form. Unlike the >30 reported FKBP12 structures, the backbone conformation of this loop closely follows that of the first FKBP domain of FKBP51. The NMR resonances for 21 backbone amides of FKBP12.6 are doubled, corresponding to a slow conformational transition centered near the tip of the 80s loop, as recently reported for 31 amides of FKBP12. The comparative absence of doubling for residues along the opposite face of the active-site pocket in FKBP12.6 may in part reflect attenuated structural coupling owing to increased conformational plasticity around the Phe59 ring

  11. Calcium binding by the PKD1 domain regulates interdomain flexibility in Vibrio cholerae metalloprotease PrtV.

    Science.gov (United States)

    Edwin, Aaron; Rompikuntal, Pramod; Björn, Erik; Stier, Gunter; Wai, Sun N; Sauer-Eriksson, A Elisabeth

    2013-01-01

    Vibrio cholerae, the causative agent of cholera, releases several virulence factors including secreted proteases when it infects its host. These factors attack host cell proteins and break down tissue barriers and cellular matrix components such as collagen, laminin, fibronectin, keratin, elastin, and they induce necrotic tissue damage. The secreted protease PrtV constitutes one virulence factors of V. cholerae. It is a metalloprotease belonging to the M6 peptidase family. The protein is expressed as an inactive, multidomain, 102 kDa pre-pro-protein that undergoes several N- and C-terminal modifications after which it is secreted as an intermediate variant of 81 kDa. After secretion from the bacteria, additional proteolytic steps occur to produce the 55 kDa active M6 metalloprotease. The domain arrangement of PrtV is likely to play an important role in these maturation steps, which are known to be regulated by calcium. However, the molecular mechanism by which calcium controls proteolysis is unknown. In this study, we report the atomic resolution crystal structure of the PKD1 domain from V. cholera PrtV (residues 755-838) determined at 1.1 Å. The structure reveals a previously uncharacterized Ca(2+)-binding site located near linker regions between domains. Conformational changes in the Ca(2+)-free and Ca(2+)-bound forms suggest that Ca(2+)-binding at the PKD1 domain controls domain linker flexibility, and plays an important structural role, providing stability to the PrtV protein.

  12. Flexible Acyclic Polyol-Chloride Anion Complexes and Their Characterization by Photoelectron Spectroscopy and Variable Temperature Binding Constant Determinations.

    Science.gov (United States)

    Shokri, Alireza; Wang, Xue-Bin; Wang, Yanping; O'Doherty, George A; Kass, Steven R

    2016-03-17

    Flexible acyclic alcohols with one to five hydroxyl groups were bound to a chloride anion and these complexes were interrogated by negative ion photoelectron spectroscopy and companion density functional theory computations. The resulting vertical detachment energies are reproduced on average to 0.10 eV by M06-2X/aug-cc-pVTZ predictions and range from 4.45-5.96 eV. These values are 0.84-2.35 eV larger than the adiabatic detachment energy of Cl(-) as a result of the larger hydrogen bond networks in the bigger polyols. Adiabatic detachment energies of the alcohol-Cl(-) clusters are more difficult to determine both experimentally and computationally. This is due to the large geometry changes that occur upon photodetachment and the large bond dissociation energy of H-Cl which enables the resulting chlorine atom to abstract a hydrogen from any of the methylene (CH2) or methine (CH) positions. Both ionic and nonionic hydrogen bonds (i.e., OH···Cl(-) and OH···OH···Cl(-)) form in the larger polyols complexes and are found to be energetically comparable. Subtle structural differences, consequently can lead to the formation of different types of hydrogen bonds, and maximizing the ionic ones is not always preferred. Solution equilibrium binding constants between the alcohols and tetrabutylammonium chloride (TBACl) in acetonitrile at -24.2, +22.0, and +53.6 °C were also determined. The free energies of association are nearly identical for all of the substrates (i.e., ΔG° = -2.8 ± 0.7 kcal mol(-1)). Compensating enthalpy and entropy values reveal, contrary to expectation and the intrinsic gas-phase preferences, that the bigger systems with more hydroxyl groups are entropically favored and enthalpically disfavored relative to the smaller species. This suggests that more solvent molecules are released upon binding TBACl to alcohols with more hydroxyl groups and is consistent with the measured negative heat capacities. These quantities increase with molecular

  13. Flexible Acyclic Polyol-Chloride Anion Complexes and Their Characterization by Photoelectron Spectroscopy and Variable Temperature Binding Constant Determinations

    Energy Technology Data Exchange (ETDEWEB)

    Shokri, Alireza; Wang, Xue B.; Wang, Yangping; O' Doherty, George A.; Kass, Steven R.

    2016-03-17

    Flexible acyclic alcohols with 1–5 hydroxyl groups were bound to chloride anion and these complexes were interrogated by negative ion photoelectron spectroscopy and companion density functional theory computations. The resulting vertical detachment energies are reproduced on average to 0.10 eV by M06-2X/aug-cc-pVTZ predictions and range from 4.45 – 5.96 eV. These values are 0.84 – 2.35 eV larger than the adiabatic detachment energy of Cl– as a result of the larger hydrogen bond networks in the bigger polyols. Adiabatic detachment energies of the alcohol–Cl– clusters are more difficult to determine both experimentally and computationally. This is due to the large geometry changes that occur upon photodetachment and the large bond dissociation energy of H–Cl which enables the resulting chlorine atom to abstract a hydrogen from any of the methylene (CH2) or methine (CH) positions. Both ionic and non-ionic hydrogen bonds (i.e., OH•••Cl– and OH•••OH•••Cl–) form in the larger polyols complexes, and are found to be energetically comparable. Subtle structural differences, consequently can lead to the formation of different types of hydrogen bonds and maximizing the ionic ones is not always preferred. Solution equilibrium binding constants between the alcohols and tetrrabuylammonium chloride (TBACl) in acetonitrile at -24.2, 22.0, and 53.6 °C were also determined. The free energies of association are nearly identical for all of the substrates (i.e., ΔG° = -2.8 ± 0.7 kcal mol–1). Compensating enthalpy and entropy values reveal, contrary to expectation and the intrinsic gas-phase preferences, that the bigger systems with more hydroxyl groups are entropically favored and enthalpically disfavored relative to the smaller species. This suggests that more solvent molecules are released upon binding TBACl to alcohols with more hydroxyl groups and is consistent with the measured negative heat capacities. These quantities increase with

  14. Antibody Binding Studies Reveal Conformational Flexibility of the Bacillus cereus Non-Hemolytic Enterotoxin (Nhe) A-Component

    Science.gov (United States)

    Märtlbauer, E.

    2016-01-01

    The non-hemolytic enterotoxin complex (Nhe) is supposed to be the main virulence factor of B. cereus causing a diarrheal outcome of food poisoning. This tripartite toxin consists of the single components NheA, -B and -C all of them being necessary for maximum toxicity. In the past, research activities aiming to elucidate the mode-of-action of Nhe were mostly focused on the B- and C-component. In this study the generation of novel monoclonal antibodies (mAb) and their thorough characterization enabled the determination of key features for NheA. By the means of immunoaffinity chromatography it could be shown that NheA does not interact with -B and -C in solution. Additionally, the establishment of a highly sensitive sandwich-EIA now enables the detection of NheA in B. cereus supernatants down to 20 pg ml-1.Peptide-based epitope mapping in combination with partially deleted recombinant NheA fragments allowed the allocation of the binding regions for the three mAbs under study. Furthermore, by different EIA set-ups the conformational flexibility of NheA could be shown. For two of the antibodies under study different mechanisms of NheA neutralization were proven. Due to prevention of complete pore formation by one of the antibodies, NheA could be detected in an intermediate stage of the tripartite complex on the cell surface. Taken together, the results obtained in the present study allow a refinement of the mode-of-action for the Nhe toxin-complex. PMID:27768742

  15. Comparative Genomic Study Reveals a Transition from TA Richness in Invertebrates to GC Richness in Vertebrates at CpG Flanking Sites: An Indication for Context-Dependent Mutagenicity of Methylated CpG Sites

    Institute of Scientific and Technical Information of China (English)

    Yong Wang; Frederick C.C. Leung

    2008-01-01

    Vertebrate genomes are characterized with CpG deficiency, particularly for GC-poor regions. The GC content-related CpG deficiency is probably caused by context-dependent deamination of methylated CpG sites. This hypothesis was examined in this study by comparing nucleotide frequencies at CpG flanking positions among invertebrate and vertebrate genomes. The finding is a transition of nucleotide preference of 5' T to 5' A at the invertebrate-vertebrate boundary, indicating that a large number of CpG sites with 5' Ts were depleted because of global DNA methylation developed in vertebrates. At genome level, we investigated CpG observed/expected (obs/exp) values in 500 bp fragments, and found that higher CpG obs/exp value is shown in GC-poor regions of invertebrate genomes (except sea urchin) but in GC-rich sequences of vertebrate genomes. We next compared GC content at CpG flanking positions with genomic average, showing that the GC content is lower than the average in invertebrate genomes, but higher than that in vertebrate genomes. These results indicate that although 5' T and 5' A are different in inducing deamination of methylated CpG sites, GC content is even more important in affecting the deamination rate. In all the tests, the results of sea urchin are similar to vertebrates perhaps due to its fractional DNA methylation.CpG deficiency is therefore suggested to be mainly a result of high mutation rates of methylated CpG sites in GC-poor regions.

  16. Flexibility of EF-hand motifs: structural and thermodynamic studies of Calcium Binding Protein-1 from Entamoeba histolytica with Pb2+, Ba2+, and Sr2+

    Directory of Open Access Journals (Sweden)

    Kumar Shivesh

    2012-08-01

    Full Text Available Abstract Background EF-hand proteins can be activated by the binding of various heavy metals other than calcium, and such complexes can disturb the calcium-signaling pathway and cause toxicity and disease causing state. So far, no comprehensive study has been done to understand different heavy metals binding to calcium signaling proteins. Results In this work, the flexibility of the EF-hand motifs are examined by crystallographic and thermodynamic studies of binding of Pb2+, Ba2+ and Sr2+ to Calcium Binding Protein-1 from Entamoeba histolytica (EhCaBP1. The structures of the EhCaBP1- heavy metal complexes are found to be overall similar, nevertheless specific differences in metal coordination, and small differences in the coordination distances between the metal and the ligands in the metal binding loop. The largest such distances occur for the Ba2+- EhCaBP1 complex, where two bariums are bound with partial occupancy at the EF2 motif. Thermodynamic studies confirm that EhCaBP1 has five binding sites for Ba2+ compared to four binding sites for the other metals. These structures and thermodynamic studies reveal that the EF-hand motifs can accommodate several heavy atoms with similar binding affinities. The binding of Ca2+ to the 1st, 2nd and 4th sites and the binding of Ba2+ to the 1st, 2nd, 4th and 5th sites are both enthalpically and entropically driven, whereas the binding of Sr2+ to the 1st, 2nd and 4th sites are simply enthalpy driven, interestingly in agreement with ITC data, Sr2+ do not coordinate with water in this structure. For all the metals, binding to the 3rd site is only entropy driven. Conclusion Energetically, Ca2+ is preferred in three sites, while in one site Ba2+ has better binding energy. The Sr2+-coordination in the EF hand motifs is similar to that of the native Ca2+ bound structure, except for the lack of water coordination. Sr2+ coordination seems to be a pre-formed in nature since all seven coordinating atoms are from the

  17. The Laminin 511/521 Binding Site on the Lutheran Blood Group Glycoprotein is Located at theFlexible Junction of Ig Domains 2 and 3

    Energy Technology Data Exchange (ETDEWEB)

    Mankelow, Tosti J.; Burton, Nicholas; Stedansdottir, Fanney O.; Spring, Frances A.; Parsons, Stephen F.; Pesersen, Jan S.; Oliveira, Cristiano L.P.; Lammie, Donna; Wess, Timothy; Mohandas, Narla; Chasis, Joel A.; Brady, R. Leo; Anstee, David J.

    2007-07-01

    The Lutheran blood group glycoprotein, first discovered on erythrocytes, is widely expressed in human tissues. It is a ligand for the {alpha}5 subunit of Laminin 511/521, an extracellular matrix protein. This interaction may contribute to vasocclusive events that are an important cause of morbidity in sickle cell disease. Using X-ray crystallography, small angle X-ray scattering and site directed mutagenesis we show that the extracellular region of Lutheran forms an extended structure with a distinctive bend between the second and third immunoglobulin-like domains. The linker between domains 2 and 3 appears to be flexible and is a critical determinant in maintaining an overall conformation for Lutheran that is capable of binding to Laminin. Mutagenesis studies indicate that Asp312 of Lutheran and the surrounding cluster of negatively charged residues in this linker region form the Laminin binding site. Unusually, receptor binding is therefore not a function of the domains expected to be furthermost from the plasma membrane. These studies imply that structural flexibility of Lutheran may be essential for its interaction with Laminin and present a novel opportunity for the development of therapeutics for sickle cell disease.

  18. Role of solution conformation and flexibility of short peptide ligands that bind to the p56(lck) SH2 domain

    NARCIS (Netherlands)

    Dekker, Frank J; de Mol, Nico J; Bultinck, Patrick; Kemmink, Johan; Hilbers, Hans W; Liskamp, Rob M J; Dekker, Frank

    2003-01-01

    A general approach in drug design is making ligands more rigid in order to avoid loss in conformational entropy (deltaS(conf)) upon receptor binding. We hypothesized that in the high affinity binding of pYEEI peptide ligands to the p56(lck) SH2 domain this loss in deltaS(conf) might be diminished du

  19. Crystal structure of TNF-α-inducing protein from Helicobacter pylori in active form reveals the intrinsic molecular flexibility for unique DNA-binding.

    Directory of Open Access Journals (Sweden)

    Mingming Gao

    Full Text Available Tipα (TNF-α-inducing protein from Helicobacter pylori is a carcinogenic effector. Studies on this protein revealed that a homodimer linked by a pair of intermolecular disulfide bridges (Cys25-Cys25 and Cys27-Cys27 was absolutely necessary for its biological functions. The activities of Tipα would be abolished when both disulfide bridges were disrupted. The crystal structures of Tipα reported to date, however, were based on inactive, monomeric mutants with their N-terminal, including residues Cys25 and Cys27, truncated. Here we report the crystal structure of H. pylori Tipα protein, TipαN(25, at 2.2Å resolution, in which Cys25 and Cys27 form a pair of inter-chain disulfide bridges linking an active dimer. The disulfide bridges exhibit structural flexibility in the present structure. A series of structure-based mutagenesis, biochemical assays and molecular dynamic simulations on DNA-Tipα interactions reveal that Tipα utilizes the dimeric interface as the DNA-binding site and that residues His60, Arg77 and Arg81 located at the interface are crucial for DNA binding. Tipα could bind to one ssDNA, two ssDNA or one dsDNA in experiments, respectively, in the native or mutant states. The unique DNA-binding activities of Tipα indicate that the intrinsic flexible nature of disulfide bridges could endow certain elasticity to the Tipα dimer for its unique bioactivities. The results shed light on the possible structural mechanism for the functional performances of Tipα.

  20. BDflex: A method for efficient treatment of molecular flexibility in calculating protein-ligand binding rate constants from Brownian dynamics simulations

    Science.gov (United States)

    Greives, Nicholas; Zhou, Huan-Xiang

    2012-10-01

    A method developed by Northrup et al. [J. Chem. Phys. 80, 1517 (1984)], 10.1063/1.446900 for calculating protein-ligand binding rate constants (ka) from Brownian dynamics (BD) simulations has been widely used for rigid molecules. Application to flexible molecules is limited by the formidable computational cost to treat conformational fluctuations during the long BD simulations necessary for ka calculation. Here, we propose a new method called BDflex for ka calculation that circumvents this problem. The basic idea is to separate the whole space into an outer region and an inner region, and formulate ka as the product of kE and bar η _d, which are obtained by separately solving exterior and interior problems. kE is the diffusion-controlled rate constant for the ligand in the outer region to reach the dividing surface between the outer and inner regions; in this exterior problem conformational fluctuations can be neglected. bar η _d is the probability that the ligand, starting from the dividing surface, will react at the binding site rather than escape to infinity. The crucial step in reducing the determination of bar η _d to a problem confined to the inner region is a radiation boundary condition imposed on the dividing surface; the reactivity on this boundary is proportional to kE. By confining the ligand to the inner region and imposing the radiation boundary condition, we avoid multiple-crossing of the dividing surface before reaction at the binding site and hence dramatically cut down the total simulation time, making the treatment of conformational fluctuations affordable. BDflex is expected to have wide applications in problems where conformational fluctuations of the molecules are crucial for productive ligand binding, such as in cases where transient widening of a bottleneck allows the ligand to access the binding pocket, or the binding site is properly formed only after ligand entrance induces the closure of a lid.

  1. Synthesis and Properties of Bis-Porphyrin Molecular Tweezers: Effects of Spacer Flexibility on Binding and Supramolecular Chirogenesis

    Directory of Open Access Journals (Sweden)

    Magnus Blom

    2015-12-01

    Full Text Available Ditopic binding of various dinitrogen compounds to three bisporphyrin molecular tweezers with spacers of varying conformational rigidity, incorporating the planar enediyne (1, the helical stiff stilbene (2, or the semi-rigid glycoluril motif fused to the porphyrins (3, are compared. Binding constants Ka = 104–106 M−1 reveal subtle differences between these tweezers, that are discussed in terms of porphyrin dislocation modes. Exciton coupled circular dichroism (ECCD of complexes with chiral dinitrogen guests provides experimental evidence for the conformational properties of the tweezers. The results are further supported and rationalized by conformational analysis.

  2. Genome-scale analysis of metazoan replication origins reveals their organization in specific but flexible sites defined by conserved features

    Science.gov (United States)

    Cayrou, Christelle; Coulombe, Philippe; Vigneron, Alice; Stanojcic, Slavica; Ganier, Olivier; Peiffer, Isabelle; Rivals, Eric; Puy, Aurore; Laurent-Chabalier, Sabine; Desprat, Romain; Méchali, Marcel

    2011-01-01

    In metazoans, thousands of DNA replication origins (Oris) are activated at each cell cycle. Their genomic organization and their genetic nature remain elusive. Here, we characterized Oris by nascent strand (NS) purification and a genome-wide analysis in Drosophila and mouse cells. We show that in both species most CpG islands (CGI) contain Oris, although methylation is nearly absent in Drosophila, indicating that this epigenetic mark is not crucial for defining the activated origin. Initiation of DNA synthesis starts at the borders of CGI, resulting in a striking bimodal distribution of NS, suggestive of a dual initiation event. Oris contain a unique nucleotide skew around NS peaks, characterized by G/T and C/A overrepresentation at the 5′ and 3′ of Ori sites, respectively. Repeated GC-rich elements were detected, which are good predictors of Oris, suggesting that common sequence features are part of metazoan Oris. In the heterochromatic chromosome 4 of Drosophila, Oris correlated with HP1 binding sites. At the chromosome level, regions rich in Oris are early replicating, whereas Ori-poor regions are late replicating. The genome-wide analysis was coupled with a DNA combing analysis to unravel the organization of Oris. The results indicate that Oris are in a large excess, but their activation does not occur at random. They are organized in groups of site-specific but flexible origins that define replicons, where a single origin is activated in each replicon. This organization provides both site specificity and Ori firing flexibility in each replicon, allowing possible adaptation to environmental cues and cell fates. PMID:21750104

  3. Flexible supercapacitors

    Institute of Scientific and Technical Information of China (English)

    Shan Shi; Chengjun Xu; Cheng Yang; Jia Li; Hongda Du; Baohua Li; Feiyu Kang

    2013-01-01

    Flexible supercapacitors show a great potential for applications in wearable,miniaturized,portable,largescale transparent and flexible consumer electronics due to their significant,inherent advantages,such as being flexible,lightweight,low cost and environmentally friendly in comparison with the current energy storage devices.In this report,recent progress on flexible supercapacitors,flexible electrodes and electrolytes is reviewed.In addition,the future challenges and opportunities are discussed.

  4. On flexibility

    OpenAIRE

    Christoph R. Weiss; Briglauer, Wolfgang

    2000-01-01

    By building on theoretical work by Mills and Schumann (1985) and Ungern-Sternberg (1990) this paper provides evidence on the determinants of two dimensions of flexibility, the flexibility in adjusting aggregate output over time (tactical flexibility) as well as the ability to switch quickly between products (operational flexibility). Econometric analysis of a sample of 40.000 farms in Upper-Austria for the period 1980 to 1990 suggests that larger full-time farms operated by younger, better ed...

  5. Molecular dynamic study of MlaC protein in Gram-negative bacteria: conformational flexibility, solvent effect and protein-phospholipid binding.

    Science.gov (United States)

    Huang, Yu-Ming M; Miao, Yinglong; Munguia, Jason; Lin, Leo; Nizet, Victor; McCammon, J Andrew

    2016-08-01

    The composition of the outer membrane in Gram-negative bacteria is asymmetric, with the lipopolysaccharides found in the outer leaflet and phospholipids in the inner leaflet. The MlaC protein transfers phospholipids from the outer to inner membrane to maintain such lipid asymmetry in the Mla pathway. In this work, we have performed molecular dynamics simulations on apo and phospholipid-bound systems to study the dynamical properties of MlaC. Our simulations show that the phospholipid forms hydrophobic interactions with the protein. Residues surrounding the entrance of the binding site exhibit correlated motions to control the site opening and closing. Lipid binding leads to increase of the binding pocket volume and precludes entry of the water molecules. However, in the absence of the phospholipid, water molecules can freely move in and out of the binding site when the pocket is open. Dehydration occurs when the pocket closes. This study provides dynamic information of the MlaC protein and may facilitate the design of antibiotics against the Mla pathway of Gram-negative bacteria. PMID:27111825

  6. STRUCTURE OF THE COMPLEX BETWEEN TRYPANOSOMAL TRIOSEPHOSPHATE ISOMERASE AND N-HYDROXY-4-PHOSPHONO-BUTANAMIDE - BINDING AT THE ACTIVE-SITE DESPITE AN OPEN FLEXIBLE LOOP CONFORMATION

    NARCIS (Netherlands)

    VERLINDE, CLMJ; WITMANS, CJ; PIJNING, T; KALK, KH; HOL, WGJ; CALLENS, M; OPPERDOES, FR

    1992-01-01

    The structure of triosephosphate isomerase from Trypanosoma brucei complexed with the competitive inhibitor N-hydroxy-4-phosphono-butanamide was determined by X-ray crystallography to a resolution of 2.84 angstrom. Full occupancy binding of the inhibitor is observed only at one of the active sites o

  7. Ligand Binding Reduces Conformational Flexibility in the Active Site of Tyrosine Phosphatase Related to Biofilm Formation A (TpbA) from Pseudomonas aeruginosa

    OpenAIRE

    Koveal, Dorothy; Clarkson, Michael W.; Wood, Thomas K.; Page, Rebecca; Peti, Wolfgang

    2013-01-01

    TpbA is a periplasmic dual specificity phosphatase (DUSP) that controls biofilm formation in the pathogenic bacterium, Pseudomonas aeruginosa. While DUSPs are known to regulate important cellular functions in both prokaryotes and eukaryotes, very few structures of bacterial DUSPs are available. Here, we present the solution structure of TpbA in the ligand-free open conformation, along with an analysis of the structural and dynamic changes that accompany ligand/phosphate binding. While TpbA ad...

  8. Conflicting flexibility

    NARCIS (Netherlands)

    De Jong, P.; Schaap, A.

    2011-01-01

    New buildings are designed for first users. For a sustainable approach there are many advantages in designing in flexibility and adjustability in order to enable and facilitate the other sequential users. For the first investor this flexibility is translated into improved exit values due to increase

  9. An encodable lanthanide binding tag with reduced size and flexibility for measuring residual dipolar couplings and pseudocontact shifts in large proteins

    Energy Technology Data Exchange (ETDEWEB)

    Barb, Adam W., E-mail: abarb@iastate.edu; Subedi, Ganesh P. [Iowa State University, Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology (United States)

    2016-01-15

    Metal ions serve important roles in structural biology applications from long-range perturbations seen in magnetic resonance experiments to electron-dense signatures in X-ray crystallography data; however, the metal ion must be secured in a molecular framework to achieve the maximum benefit. Polypeptide-based lanthanide-binding tags (LBTs) represent one option that can be directly encoded within a recombinant protein expression construct. However, LBTs often exhibit significant mobility relative to the target molecule. Here we report the characterization of improved LBTs sequences for insertion into a protein loop. These LBTs were inserted to connect two parallel alpha helices of an immunoglobulin G (IgG)-binding Z domain platform. Variants A and B bound Tb{sup 3+} with high affinity (0.70 and 0.13 μM, respectively) and displayed restricted LBT motion. Compared to the parent construct, the metal-bound A experienced a 2.5-fold reduction in tag motion as measured by magnetic field-induced residual dipolar couplings and was further studied in a 72.2 kDa complex with the human IgG1 fragment crystallizable (IgG1 Fc) glycoprotein. The appearance of both pseudo-contact shifts (−0.221 to 0.081 ppm) and residual dipolar couplings (−7.6 to 14.3 Hz) of IgG1 Fc resonances in the IgG1 Fc:(variant A:Tb{sup 3+}){sub 2} complex indicated structural restriction of the LBT with respect to the Fc. These studies highlight the applicability of improved LBT sequences with reduced mobility to probe the structure of macromolecular systems.

  10. An encodable lanthanide binding tag with reduced size and flexibility for measuring residual dipolar couplings and pseudocontact shifts in large proteins.

    Science.gov (United States)

    Barb, Adam W; Subedi, Ganesh P

    2016-01-01

    Metal ions serve important roles in structural biology applications from long-range perturbations seen in magnetic resonance experiments to electron-dense signatures in X-ray crystallography data; however, the metal ion must be secured in a molecular framework to achieve the maximum benefit. Polypeptide-based lanthanide-binding tags (LBTs) represent one option that can be directly encoded within a recombinant protein expression construct. However, LBTs often exhibit significant mobility relative to the target molecule. Here we report the characterization of improved LBTs sequences for insertion into a protein loop. These LBTs were inserted to connect two parallel alpha helices of an immunoglobulin G (IgG)-binding Z domain platform. Variants A and B bound Tb(3+) with high affinity (0.70 and 0.13 μM, respectively) and displayed restricted LBT motion. Compared to the parent construct, the metal-bound A experienced a 2.5-fold reduction in tag motion as measured by magnetic field-induced residual dipolar couplings and was further studied in a 72.2 kDa complex with the human IgG1 fragment crystallizable (IgG1 Fc) glycoprotein. The appearance of both pseudo-contact shifts (-0.221 to 0.081 ppm) and residual dipolar couplings (-7.6 to 14.3 Hz) of IgG1 Fc resonances in the IgG1 Fc:(variant A:Tb(3+))2 complex indicated structural restriction of the LBT with respect to the Fc. These studies highlight the applicability of improved LBT sequences with reduced mobility to probe the structure of macromolecular systems. PMID:26728077

  11. An encodable lanthanide binding tag with reduced size and flexibility for measuring residual dipolar couplings and pseudocontact shifts in large proteins

    International Nuclear Information System (INIS)

    Metal ions serve important roles in structural biology applications from long-range perturbations seen in magnetic resonance experiments to electron-dense signatures in X-ray crystallography data; however, the metal ion must be secured in a molecular framework to achieve the maximum benefit. Polypeptide-based lanthanide-binding tags (LBTs) represent one option that can be directly encoded within a recombinant protein expression construct. However, LBTs often exhibit significant mobility relative to the target molecule. Here we report the characterization of improved LBTs sequences for insertion into a protein loop. These LBTs were inserted to connect two parallel alpha helices of an immunoglobulin G (IgG)-binding Z domain platform. Variants A and B bound Tb3+ with high affinity (0.70 and 0.13 μM, respectively) and displayed restricted LBT motion. Compared to the parent construct, the metal-bound A experienced a 2.5-fold reduction in tag motion as measured by magnetic field-induced residual dipolar couplings and was further studied in a 72.2 kDa complex with the human IgG1 fragment crystallizable (IgG1 Fc) glycoprotein. The appearance of both pseudo-contact shifts (−0.221 to 0.081 ppm) and residual dipolar couplings (−7.6 to 14.3 Hz) of IgG1 Fc resonances in the IgG1 Fc:(variant A:Tb3+)2 complex indicated structural restriction of the LBT with respect to the Fc. These studies highlight the applicability of improved LBT sequences with reduced mobility to probe the structure of macromolecular systems

  12. Binding water to a PEG-linked flexible bichromophore: IR spectra of diphenoxyethane-(H2O)n clusters, n = 2-4

    International Nuclear Information System (INIS)

    The single-conformation infrared (IR) and ultraviolet (UV) spectroscopies of neutral 1,2-diphenoxyethane-(H2O)n clusters with n = 2-4 (labeled henceforth as 1:n) have been studied in a molecular beam using a combination of resonant two-photon ionization, IR-UV holeburning, and resonant ion-dip infrared (RIDIR) spectroscopies. Ground state RIDIR spectra in the OH and CH stretch regions were used to provide firm assignments for the structures of the clusters by comparing the experimental spectra with the predictions of calculations carried out at the density functional M05-2X/6-31+G(d) level of theory. At all sizes in this range, the water molecules form water clusters in which all water molecules engage in a single H-bonded network. Selective binding to the tgt monomer conformer of 1,2-diphenoxyethane (C6H5-O-CH2-CH2-O-C6H5, DPOE) occurs, since this conformer provides a binding pocket in which the two ether oxygens and two phenyl ring π clouds can be involved in stabilizing the water cluster. The 1:2 cluster incorporates a water dimer “chain” bound to DPOE much as it is in the 1:1 complex [E. G. Buchanan et al., J. Phys. Chem. Lett. 4, 1644 (2013)], with primary attachment via a double-donor water that bridges the ether oxygen of one phenoxy group and the π cloud of the other. Two conformers of the 1:3 cluster are observed and characterized, one that extends the water chain to a third molecule (1:3 chain) and the other incorporating a water trimer cycle (1:3 cycle). A cyclic water structure is also observed for the 1:4 cluster. These structural characterizations provide a necessary foundation for studies of the perturbations imposed on the two close-lying S1/S2 excited states of DPOE considered in the adjoining paper [P. S. Walsh et al., J. Chem. Phys. 142, 154304 (2015)

  13. Binding water to a PEG-linked flexible bichromophore: IR spectra of diphenoxyethane-(H2O)n clusters, n = 2-4

    Science.gov (United States)

    Walsh, Patrick S.; Buchanan, Evan G.; Gord, Joseph R.; Zwier, Timothy S.

    2015-04-01

    The single-conformation infrared (IR) and ultraviolet (UV) spectroscopies of neutral 1,2-diphenoxyethane-(H2O)n clusters with n = 2-4 (labeled henceforth as 1:n) have been studied in a molecular beam using a combination of resonant two-photon ionization, IR-UV holeburning, and resonant ion-dip infrared (RIDIR) spectroscopies. Ground state RIDIR spectra in the OH and CH stretch regions were used to provide firm assignments for the structures of the clusters by comparing the experimental spectra with the predictions of calculations carried out at the density functional M05-2X/6-31+G(d) level of theory. At all sizes in this range, the water molecules form water clusters in which all water molecules engage in a single H-bonded network. Selective binding to the tgt monomer conformer of 1,2-diphenoxyethane (C6H5-O-CH2-CH2-O-C6H5, DPOE) occurs, since this conformer provides a binding pocket in which the two ether oxygens and two phenyl ring π clouds can be involved in stabilizing the water cluster. The 1:2 cluster incorporates a water dimer "chain" bound to DPOE much as it is in the 1:1 complex [E. G. Buchanan et al., J. Phys. Chem. Lett. 4, 1644 (2013)], with primary attachment via a double-donor water that bridges the ether oxygen of one phenoxy group and the π cloud of the other. Two conformers of the 1:3 cluster are observed and characterized, one that extends the water chain to a third molecule (1:3 chain) and the other incorporating a water trimer cycle (1:3 cycle). A cyclic water structure is also observed for the 1:4 cluster. These structural characterizations provide a necessary foundation for studies of the perturbations imposed on the two close-lying S1/S2 excited states of DPOE considered in the adjoining paper [P. S. Walsh et al., J. Chem. Phys. 142, 154304 (2015)].

  14. Binding water to a PEG-linked flexible bichromophore: IR spectra of diphenoxyethane-(H{sub 2}O){sub n} clusters, n = 2-4

    Energy Technology Data Exchange (ETDEWEB)

    Walsh, Patrick S.; Buchanan, Evan G.; Gord, Joseph R.; Zwier, Timothy S., E-mail: zwier@purdue.edu [Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907-2084 (United States)

    2015-04-21

    The single-conformation infrared (IR) and ultraviolet (UV) spectroscopies of neutral 1,2-diphenoxyethane-(H{sub 2}O){sub n} clusters with n = 2-4 (labeled henceforth as 1:n) have been studied in a molecular beam using a combination of resonant two-photon ionization, IR-UV holeburning, and resonant ion-dip infrared (RIDIR) spectroscopies. Ground state RIDIR spectra in the OH and CH stretch regions were used to provide firm assignments for the structures of the clusters by comparing the experimental spectra with the predictions of calculations carried out at the density functional M05-2X/6-31+G(d) level of theory. At all sizes in this range, the water molecules form water clusters in which all water molecules engage in a single H-bonded network. Selective binding to the tgt monomer conformer of 1,2-diphenoxyethane (C{sub 6}H{sub 5}-O-CH{sub 2}-CH{sub 2}-O-C{sub 6}H{sub 5}, DPOE) occurs, since this conformer provides a binding pocket in which the two ether oxygens and two phenyl ring π clouds can be involved in stabilizing the water cluster. The 1:2 cluster incorporates a water dimer “chain” bound to DPOE much as it is in the 1:1 complex [E. G. Buchanan et al., J. Phys. Chem. Lett. 4, 1644 (2013)], with primary attachment via a double-donor water that bridges the ether oxygen of one phenoxy group and the π cloud of the other. Two conformers of the 1:3 cluster are observed and characterized, one that extends the water chain to a third molecule (1:3 chain) and the other incorporating a water trimer cycle (1:3 cycle). A cyclic water structure is also observed for the 1:4 cluster. These structural characterizations provide a necessary foundation for studies of the perturbations imposed on the two close-lying S{sub 1}/S{sub 2} excited states of DPOE considered in the adjoining paper [P. S. Walsh et al., J. Chem. Phys. 142, 154304 (2015)].

  15. Flexible sheaves

    CERN Document Server

    Simpson, C

    1996-01-01

    We treat a non-associative version (``flexible presheaf'') of the notion of simplicial presheaf or presheaf of spaces on a site. We define the notion of $n$-truncated flexible sheaf or homotopy-sheaf, and give a construction of the homotopy-sheafification of a flexible sheaf by applying a certain natural operation $n+2$ times. We give a definition of morphism of flexible sheaves as well as the internal $Hom$. The notion of ($n$-truncated) flexible sheaf is a precursor to the notion of $n$-stack. After 1993 I learned of Jardine's earlier theory which, in view of our strictification result, seems to encompass the main part of what is done here. I am finally putting this on the archive because there may be some details of what we do here which are different from what Jardine does and useful in their own right. For example we give a way of strictifying into a presheaf of spaces; we define a weakly associative notion of composition, which leads among other things to a canonical inversion of homotopy equivalences (...

  16. Functional aspects of protein flexibility

    DEFF Research Database (Denmark)

    Teilum, Kaare; Olsen, Johan G; Kragelund, Birthe B

    2009-01-01

    Proteins are dynamic entities, and they possess an inherent flexibility that allows them to function through molecular interactions within the cell, among cells and even between organisms. Appreciation of the non-static nature of proteins is emerging, but to describe and incorporate...... this into an intuitive perception of protein function is challenging. Flexibility is of overwhelming importance for protein function, and the changes in protein structure during interactions with binding partners can be dramatic. The present review addresses protein flexibility, focusing on protein-ligand interactions....... The thermodynamics involved are reviewed, and examples of structure-function studies involving experimentally determined flexibility descriptions are presented. While much remains to be understood about protein flexibility, it is clear that it is encoded within their amino acid sequence and should be viewed...

  17. Flexible Capitalism

    DEFF Research Database (Denmark)

    the perspective offers new ways to enquire about the flexible capitalism’s social dimensions. The essays contribute to a trans-disciplinary scholarship on contemporary economic practice and change by documenting how, across diverse settings, “gift-like” socialities proliferate, and even sustain the intensified......Approaching “work” as at heart a practice of exchange, this volume explores sociality in work environments marked by the kind of structural changes that have come to define contemporary “flexible” capitalism. It introduces anthropological exchange theory to a wider readership, and shows how...... flexible commoditization that more commonly is touted as tearing social relations apart. By interrogating a keenly debated contemporary work regime through an approach to sociality rooted in a rich and distinct anthropological legacy, the volume also makes a novel contribution to the anthropological...

  18. Proto-oncogene FBI-1 (Pokemon/ZBTB7A) Represses Transcription of the Tumor Suppressor Rb Gene via Binding Competition with Sp1 and Recruitment of Co-repressors*S⃞

    OpenAIRE

    Jeon, Bu-Nam; Yoo, Jung-Yoon; Choi, Won-Il; Lee, Choong-Eun; Yoon, Ho-Geun; Hur, Man-Wook

    2008-01-01

    FBI-1 (also called Pokemon/ZBTB7A) is a BTB/POZ-domain Krüppel-like zinc-finger transcription factor. Recently, FBI-1 was characterized as a proto-oncogenic protein, which represses tumor suppressor ARF gene transcription. The expression of FBI-1 is increased in many cancer tissues. We found that FBI-1 potently represses transcription of the Rb gene, a tumor suppressor gene important in cell cycle arrest. FBI-1 binds to four GC-rich promoter elements (FREs) located at ...

  19. Genetic flexibility of regulatory networks.

    Science.gov (United States)

    Hunziker, Alexander; Tuboly, Csaba; Horváth, Péter; Krishna, Sandeep; Semsey, Szabolcs

    2010-07-20

    Gene regulatory networks are based on simple building blocks such as promoters, transcription factors (TFs) and their binding sites on DNA. But how diverse are the functions that can be obtained by different arrangements of promoters and TF binding sites? In this work we constructed synthetic regulatory regions using promoter elements and binding sites of two noninteracting TFs, each sensing a single environmental input signal. We show that simply by combining these three kinds of elements, we can obtain 11 of the 16 Boolean logic gates that integrate two environmental signals in vivo. Further, we demonstrate how combination of logic gates can result in new logic functions. Our results suggest that simple elements of transcription regulation form a highly flexible toolbox that can generate diverse functions under natural selection.

  20. FLEXIBILITY IN AGRICULTURE

    OpenAIRE

    Christoph R. Weiss

    1999-01-01

    This paper considers the determinants of two dimensions of flexibility, the flexibility in adjusting aggregate output over time ("tactical flexibility") as well as the ability to switch quickly between products ("operational flexibility"). Econometric analysis of a sample of 40,000 farms in Upper-Austria for the period 1980 to 1990 suggests that larger full-time farms operated by younger, better educated farm operators are more flexible, ceteris paribus. The results further indicate a signifi...

  1. Docking to flexible nicotinic acetylcholine receptors

    DEFF Research Database (Denmark)

    Sander, Tommy; Bruun, Anne T; Balle, Thomas

    2010-01-01

    Computational docking to nicotinic acetylcholine receptors (nAChRs) and other members of the Cys-loop receptor family is complicated by the flexibility of the so-called C-loop. As observed in the large number of published crystal structures of the acetylcholine binding protein (AChBP), a structural...

  2. Specificity and affinity quantification of flexible recognition from underlying energy landscape topography.

    Directory of Open Access Journals (Sweden)

    Xiakun Chu

    2014-08-01

    Full Text Available Flexibility in biomolecular recognition is essential and critical for many cellular activities. Flexible recognition often leads to moderate affinity but high specificity, in contradiction with the conventional wisdom that high affinity and high specificity are coupled. Furthermore, quantitative understanding of the role of flexibility in biomolecular recognition is still challenging. Here, we meet the challenge by quantifying the intrinsic biomolecular recognition energy landscapes with and without flexibility through the underlying density of states. We quantified the thermodynamic intrinsic specificity by the topography of the intrinsic binding energy landscape and the kinetic specificity by association rate. We found that the thermodynamic and kinetic specificity are strongly correlated. Furthermore, we found that flexibility decreases binding affinity on one hand, but increases binding specificity on the other hand, and the decreasing or increasing proportion of affinity and specificity are strongly correlated with the degree of flexibility. This shows more (less flexibility leads to weaker (stronger coupling between affinity and specificity. Our work provides a theoretical foundation and quantitative explanation of the previous qualitative studies on the relationship among flexibility, affinity and specificity. In addition, we found that the folding energy landscapes are more funneled with binding, indicating that binding helps folding during the recognition. Finally, we demonstrated that the whole binding-folding energy landscapes can be integrated by the rigid binding and isolated folding energy landscapes under weak flexibility. Our results provide a novel way to quantify the affinity and specificity in flexible biomolecular recognition.

  3. Global Sourcing Flexibility

    DEFF Research Database (Denmark)

    Ørberg Jensen, Peter D.; Petersen, Bent

    2013-01-01

    sourcing flexibility. Here we draw on prior research in the fields of organizational flexibility, international business and global sourcing as well as case examples and secondary studies. In the second part of the paper, we discuss the implications of global sourcing flexibility for firm strategy...... the higher costs (but decreased risk for value chain disruption) embedded in a more flexible global sourcing model that allows the firm to replicate and/or relocate activities across multiple locations. We develop a model and propositions on facilitating and constraining conditions of global sourcing...... flexibility. We finally discuss implications for management and international business research, within and beyond the domain of global services sourcing....

  4. Methods for sequencing GC-rich and CCT repeat DNA templates

    Science.gov (United States)

    Robinson, Donna L.

    2007-02-20

    The present invention is directed to a PCR-based method of cycle sequencing DNA and other polynucleotide sequences having high CG content and regions of high GC content, and includes for example DNA strands with a high Cytosine and/or Guanosine content and repeated motifs such as CCT repeats.

  5. The structure of truncated recombinant human bile salt-stimulated lipase reveals bile salt-independent conformational flexibility at the active-site loop and provides insights into heparin binding.

    Science.gov (United States)

    Moore, S A; Kingston, R L; Loomes, K M; Hernell, O; Bläckberg, L; Baker, H M; Baker, E N

    2001-09-21

    Human bile salt-stimulated lipase (BSSL), which is secreted from the pancreas into the digestive tract and from the lactating mammary gland into human milk, is important for the effective absorption of dietary lipids. The dependence of BSSL on bile acids for activity with water-insoluble substrates differentiates it from other lipases. We have determined the crystal structure of a truncated variant of human BSSL (residues 1-5.8) and refined it at 2.60 A resolution, to an R-factor of 0.238 and R(free) of 0.275. This variant lacks the C-terminal alpha-helix and tandem C-terminal repeat region of native BSSL, but retains full catalytic activity. A short loop (residues 115-126) capable of occluding the active-site (the active site loop) is highly mobile and exists in two conformations, the most predominant of which leaves the active-site open for interactions with substrate. The bile salt analogue 3-[(3-cholamidopropyl)dimethylammonio]-1-propane sulfonic acid (CHAPS) was present in the crystallisation medium, but was not observed bound to the enzyme. However, the structure reveals a sulfonate group from the buffer piperizine ethane sulfonic acid (PIPES), making interactions with Arg63 and His115. His115 is part of the active-site loop, indicating that the loop could participate in the binding of a sulphate group from either the glycosaminoglycan heparin (known to bind BSSL) or a bile acid such as deoxycholate. Opening of the 115-126 active-site loop may be cooperatively linked to a sulphate anion binding at this site. The helix bundle domain of BSSL (residues 319-398) exhibits weak electron density and high temperature factors, indicating considerable structural mobility. This domain contains an unusual Asp:Glu pair buried in a hydrophobic pocket between helices alpha(H) and alpha(K) that may be functionally important. We have also solved the structure of full-length glycosylated human BSSL at 4.1 A resolution, using the refined coordinates of the truncated molecule as

  6. Flexible magnetoimpidence sensor

    KAUST Repository

    Kavaldzhiev, M. N.

    2015-05-01

    Recently, flexible electronic devices have attracted increasing interest, due to the opportunities they promise for new applications such as wearable devices, where the components are required to flex during normal use[1]. In this light, different magnetic sensors, like microcoil, spin valve, giant magnetoresistance (GMR), magnetoimpedance (MI), have been studied previously on flexible substrates.

  7. Shield For Flexible Pipe

    Science.gov (United States)

    Ponton, Michael K.; Williford, Clifford B.; Lagen, Nicholas T.

    1995-01-01

    Cylindrical shield designed to fit around flexible pipe to protect nearby workers from injury and equipment from damage if pipe ruptures. Designed as pressure-relief device. Absorbs impact of debris ejected radially from broken flexible pipe. Also redirects flow of pressurized fluid escaping from broken pipe onto flow path allowing for relief of pressure while minimizing potential for harm.

  8. Reversibly Bistable Flexible Electronics

    KAUST Repository

    Alfaraj, Nasir

    2015-05-01

    Introducing the notion of transformational silicon electronics has paved the way for integrating various applications with silicon-based, modern, high-performance electronic circuits that are mechanically flexible and optically semitransparent. While maintaining large-scale production and prototyping rapidity, this flexible and translucent scheme demonstrates the potential to transform conventionally stiff electronic devices into thin and foldable ones without compromising long-term performance and reliability. In this work, we report on the fabrication and characterization of reversibly bistable flexible electronic switches that utilize flexible n-channel metal-oxide-semiconductor field-effect transistors. The transistors are fabricated initially on rigid (100) silicon substrates before they are peeled off. They can be used to control flexible batches of light-emitting diodes, demonstrating both the relative ease of scaling at minimum cost and maximum reliability and the feasibility of integration. The peeled-off silicon fabric is about 25 µm thick. The fabricated devices are transferred to a reversibly bistable flexible platform through which, for example, a flexible smartphone can be wrapped around a user’s wrist and can also be set back to its original mechanical position. Buckling and cyclic bending of such host platforms brings a completely new dimension to the development of flexible electronics, especially rollable displays.

  9. Flexible Carbon Aerogels

    Directory of Open Access Journals (Sweden)

    Marina Schwan

    2016-09-01

    Full Text Available Carbon aerogels are highly porous materials with a large inner surface area. Due to their high electrical conductivity they are excellent electrode materials in supercapacitors. Their brittleness, however, imposes certain limitations in terms of applicability. In that context, novel carbon aerogels with varying degree of flexibility have been developed. These highly porous, light aerogels are characterized by a high surface area and possess pore structures in the micrometer range, allowing for a reversible deformation of the aerogel network. A high ratio of pore size to particle size was found to be crucial for high flexibility. For dynamic microstructural analysis, compression tests were performed in-situ within a scanning electron microscope allowing us to directly visualize the microstructural flexibility of an aerogel. The flexible carbon aerogels were found to withstand between 15% and 30% of uniaxial compression in a reversible fashion. These findings might stimulate further research and new application fields directed towards flexible supercapacitors and batteries.

  10. Flexible ferroelectric organic crystals

    Science.gov (United States)

    Owczarek, Magdalena; Hujsak, Karl A.; Ferris, Daniel P.; Prokofjevs, Aleksandrs; Majerz, Irena; Szklarz, Przemysław; Zhang, Huacheng; Sarjeant, Amy A.; Stern, Charlotte L.; Jakubas, Ryszard; Hong, Seungbum; Dravid, Vinayak P.; Stoddart, J. Fraser

    2016-10-01

    Flexible organic materials possessing useful electrical properties, such as ferroelectricity, are of crucial importance in the engineering of electronic devices. Up until now, however, only ferroelectric polymers have intrinsically met this flexibility requirement, leaving small-molecule organic ferroelectrics with room for improvement. Since both flexibility and ferroelectricity are rare properties on their own, combining them in one crystalline organic material is challenging. Herein, we report that trisubstituted haloimidazoles not only display ferroelectricity and piezoelectricity--the properties that originate from their non-centrosymmetric crystal lattice--but also lend their crystalline mechanical properties to fine-tuning in a controllable manner by disrupting the weak halogen bonds between the molecules. This element of control makes it possible to deliver another unique and highly desirable property, namely crystal flexibility. Moreover, the electrical properties are maintained in the flexible crystals.

  11. Flexible ferroelectric organic crystals

    Science.gov (United States)

    Owczarek, Magdalena; Hujsak, Karl A.; Ferris, Daniel P.; Prokofjevs, Aleksandrs; Majerz, Irena; Szklarz, Przemysław; Zhang, Huacheng; Sarjeant, Amy A.; Stern, Charlotte L.; Jakubas, Ryszard; Hong, Seungbum; Dravid, Vinayak P.; Stoddart, J. Fraser

    2016-01-01

    Flexible organic materials possessing useful electrical properties, such as ferroelectricity, are of crucial importance in the engineering of electronic devices. Up until now, however, only ferroelectric polymers have intrinsically met this flexibility requirement, leaving small-molecule organic ferroelectrics with room for improvement. Since both flexibility and ferroelectricity are rare properties on their own, combining them in one crystalline organic material is challenging. Herein, we report that trisubstituted haloimidazoles not only display ferroelectricity and piezoelectricity—the properties that originate from their non-centrosymmetric crystal lattice—but also lend their crystalline mechanical properties to fine-tuning in a controllable manner by disrupting the weak halogen bonds between the molecules. This element of control makes it possible to deliver another unique and highly desirable property, namely crystal flexibility. Moreover, the electrical properties are maintained in the flexible crystals. PMID:27734829

  12. Synthesis and DNA-binding Study of Ruthenium (Ⅱ)Complexes Containing Flexible Intercalative Ligand%含柔性插入配体的钌(Ⅱ)配合物的合成及其与DNA作用研究

    Institute of Scientific and Technical Information of China (English)

    刘意; 刘云军

    2009-01-01

    设计合成一个柔性插入配体dcpip(dcpip=2-(2,3-环己烯基咪唑并[4,5-f]邻菲略啉)及其钌(Ⅱ)多吡啶配合物[Ru(bpy)2(dcpip)](ClO4)2(bpy=2,2'-联吡啶)和[Ru(phen)2(dcpip)](ClO4):(phen=1,10-邻菲咯啉).采用元素分析和质谱对其进行表征.用电子吸收光谱、荧光光谱和粘度测试研究配合物与DNA作用.研究结果表明,配合物与DNA之间通过插入作用结合.%A new ligand dcpip and its ruthenium(Ⅱ) complexes [Ru(bpy)2 (dcpip)]2+ (bpy = 2,2'-bipyridine) and [Ru(phen)2(dcpip)]2+ (phen = 1,10-phenanthroline, dcpip = 2-(2,3-cyclohexenyl)imidazo[4,5-f][1,10]phenanthroline)were synthesized and characterized by elemental analysis and mass spectra. The DNA-binding properties of these complexes were investigated by spectroscopic methods and viscosity measurement. The experimental results indicated that the two complexes interact with calf thymus DNA (CT-DNA) by intercalative mode.

  13. Painful Flexible Flatfoot.

    Science.gov (United States)

    Sheikh Taha, Abdel Majid; Feldman, David S

    2015-12-01

    Flatfoot is commonly encountered by pediatric orthopedic surgeons and pediatricians. A paucity of literature exists on how to define a flatfoot. The absence of the medial arch with a valgus hindfoot is the hallmark of this pathology. Flatfoot can be flexible or rigid. This review focuses on the diagnosis and treatment of the flexible flatfoot. Most flatfeet are flexible and clinically asymptomatic, and warrant little intervention. If feet are symptomatic, treatment is needed. Most patients who require treatment improve with foot orthotics and exercises. Only feet resistant to conservative modalities are deemed surgical candidates. The presence of a tight heel cord is often found in patients who fail conservative management.

  14. Binding of the biogenic polyamines to deoxyribonucleic acids of varying base composition: base specificity and the associated energetics of the interaction.

    Directory of Open Access Journals (Sweden)

    Ayesha Kabir

    Full Text Available BACKGROUND: The thermodynamics of the base pair specificity of the binding of the polyamines spermine, spermidine, putrescine, and cadaverine with three genomic DNAs Clostridium perfringens, 27% GC, Escherichia coli, 50% GC and Micrococcus lysodeikticus, 72% GC have been studied using titration calorimetry and the data supplemented with melting studies, ethidium displacement and circular dichroism spectroscopy results. METHODOLOGY/PRINCIPAL FINDINGS: Isothermal titration calorimetry, differential scanning calorimetry, optical melting studies, ethidium displacement, circular dichroism spectroscopy are the various techniques employed to characterize the interaction of four polyamines, spermine, spermidine, putersine and cadaverine with the DNAs. Polyamines bound stronger with AT rich DNA compared to the GC rich DNA and the binding varied depending on the charge on the polyamine as spermine>spermidine >putrescine>cadaverine. Thermodynamics of the interaction revealed that the binding was entropy driven with small enthalpy contribution. The binding was influenced by salt concentration suggesting the contribution from electrostatic forces to the Gibbs energy of binding to be the dominant contributor. Each system studied exhibited enthalpy-entropy compensation. The negative heat capacity changes suggested a role for hydrophobic interactions which may arise due to the non polar interactions between DNA and polyamines. CONCLUSION/SIGNIFICANCE: From a thermodynamic analysis, the AT base specificity of polyamines to DNAs has been elucidated for the first time and supplemented by structural studies.

  15. Wage Flexibility in Contemporary Society

    OpenAIRE

    Silviu Alexandru TECULESCU

    2008-01-01

    The present article has as an objective to offer the most efficient solutions so that our country reach the level of economic development associated to the West European states. It proposes the division of flexibility in three components, namely: internal flexibility, external flexibility and wage flexibility. The analysis performed within the present study will emphasize the wage flexibility. Wage flexibility can be classified in four components: ¦S Plans of individual and group incentives; ...

  16. Flexible displays, rigid designs?

    DEFF Research Database (Denmark)

    Hornbæk, Kasper

    2015-01-01

    Rapid technological progress has enabled a wide range of flexible displays for computing devices, but the user experience--which we're only beginning to understand--will be the key driver for successful designs....

  17. Flexible Audio Coder

    OpenAIRE

    Asteborg, Marcus

    2011-01-01

    As modern communications networks are heterogeneous and, therefore, highly variable, the design of source coders should reflect this network variability. It is desired that source coders are able to adapt instantly to any bit-rate constraint. Source coders that possess this property offer coding flexibility that facilitates optimal utilization of the available communication channel within a heterogeneous network. Flexible coders are able to utilize feedback information and therefore perform a...

  18. COUPLING EFFECT OF FLEXIBLE JOINT AND FLEXIBLE LINK ON DYNAMIC SINGULARITY OF FLEXIBLE MANIPULATOR

    Institute of Scientific and Technical Information of China (English)

    GAO Zhihui; YUN Chao; BIAN Yushu

    2008-01-01

    The coupling effect of the flexible joint and the flexible link on the dynamic singularity of the flexible manipulator is addressed. Firstly, the dynamic equations of a flexible manipulator with a flexible joint and a flexible link are derived. Secondly, the relationship and property between the flexible joint and the flexible link are analyzed. It shows that the flexible joint's amplitude will increase abruptly, thereby the dynamic singularity occurs if the frequency of a flexible joint is near or equal to some natural frequency of a flexible link. Finally, some numerical simulations which will verify the correctness of the theoretical analysis, are carried out. The results are fundamental for the design of a flexible manipulator and for the avoidance of the dynamic singularity.

  19. Binding Procurement

    Science.gov (United States)

    Rao, Gopalakrishna M.; Vaidyanathan, Hari

    2007-01-01

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

  20. Flexible magnetoimpedance sensor

    Energy Technology Data Exchange (ETDEWEB)

    Li, Bodong; Kavaldzhiev, Mincho N.; Kosel, Jürgen, E-mail: jurgen.kosel@kaust.edu.sa

    2015-03-15

    Flexible magnetoimpedance (MI) sensors fabricated using a NiFe/Cu/NiFe tri-layer on Kapton substrate have been studied. A customized flexible microstrip transmission line was employed to investigate the MI sensors's magnetic field and frequency responses and their dependence on the sensors's deflection. For the first time, the impedance characteristic is obtained through reflection coefficient analysis over a wide range of frequencies from 0.1 MHz to 3 GHz and for deflections ranging from zero curvature to a radius of 7.2 cm. The sensor element maintains a high MI ratio of up to 90% and magnetic sensitivity of up to 9.2%/Oe over different bending curvatures. The relationship between the curvature and material composition is discussed based on the magnetostriction effect and stress simulations. The sensor's large frequency range, simple fabrication process and high sensitivity provide a great potential for flexible electronics and wireless applications. - Highlights: • A flexible magnetoimpedance (MI) sensor is developed. • Studies are carried out using a flexible microstrip transmission line. • An MI ratio of up to 90% is obtained. • The effect of magnetostriction is studied.

  1. Flexible sucker rod unit

    Energy Technology Data Exchange (ETDEWEB)

    Allen, L.F.

    1987-02-03

    This patent describes a deep well having: a. an education tube with an inside diameter extending from the surface of the earth to far below the surface, b. a reciprocating pump housing attached to the bottom of the education tube, c. pump jack means at the surface for reciprocating the pump, d. a light sucker rod connected to the pump jack means and extending into the education tube, and e. a series of heavy sinker bars having a large cross sectional area in the education tube connecting the light sucker rod to the pump; f. an improved integral metal flexible rod unit interconnecting the sinker bars comprising in combination with the above: g. a coupling on each end of the integral metal flexible rod unit connecting the flexible rod unit to the contiguous sinker bar, h. a segment which is flexible as compared to the sinker bars connecting one of the couplings to i. an integral metal bearing adjacent to the other of the couplings, the bearing having j. a cylindrical surface with k. a diameter i. only slightly smaller than the inside diameter of the education tube thereby forming a sliding fit therewith, and ii. greater than the diameter of any other portion of the flexible rod unit and the sinker bar, and l. grooves in the cylindrical surface for the passage of fluid between in the education tube around the bearing.

  2. Measuring and Comparing Energy Flexibilities

    DEFF Research Database (Denmark)

    Valsomatzis, Emmanouil; Hose, Katja; Pedersen, Torben Bach;

    2015-01-01

    /or amount explicitly. However, in order to manage and price the flexibilities of flex-offers effectively, we must first be able to measure these flexibilities and compare them to each other. In this paper, we propose a number of possible flexibility definitions for flex-offers. We consider flexibility...

  3. Service-based flexible workflow system for virtual enterprise

    Institute of Scientific and Technical Information of China (English)

    WU Shao-fei

    2008-01-01

    Using the services provided by virtual enterprises, we presented a solution to implement flexible inter-enterprise workflow management. Services were the responses of events that can be accessed programmatically on the Internet by HTTP protocol. Services were obtained according to some standardized service templates. The workflow engine's flexible control to a request was bound to appropriate services and their providers by using a constraint-based, dynamic binding mechanism. Hence, a flexible and collaborative business was achieved. The workflow management system supports virtual enterprise, and the styles of virtual enterprises can be adjusted readily to adapt various situations.

  4. Flexible magnetoimpedance sensor

    KAUST Repository

    Li, Bodong

    2015-03-01

    Flexible magnetoimpedance (MI) sensors fabricated using a NiFe/Cu/NiFe tri-layer on Kapton substrate have been studied. A customized flexible microstrip transmission line was employed to investigate the MI sensors\\'s magnetic field and frequency responses and their dependence on the sensors\\'s deflection. For the first time, the impedance characteristic is obtained through reflection coefficient analysis over a wide range of frequencies from 0.1 MHz to 3 GHz and for deflections ranging from zero curvature to a radius of 7.2 cm. The sensor element maintains a high MI ratio of up to 90% and magnetic sensitivity of up to 9.2%/Oe over different bending curvatures. The relationship between the curvature and material composition is discussed based on the magnetostriction effect and stress simulations. The sensor\\'s large frequency range, simple fabrication process and high sensitivity provide a great potential for flexible electronics and wireless applications.

  5. Chaperone-assisted translocation of flexible polymers in three dimensions

    CERN Document Server

    Suhonen, P M

    2016-01-01

    Polymer translocation through a nanometer-scale pore assisted by chaperones binding to the polymer is a process encountered in vivo for proteins. Studying the relevant models by computer simulations is computationally demanding. Accordingly, previous studies are either for stiff polymers in three dimensions or flexible polymers in two dimensions. Here, we study chaperone-assisted translocation of flexible polymers in three dimensions using Langevin dynamics. We show that differences in binding mechanisms, more specifically, whether a chaperone can bind to a single or multiple sites on the polymer, lead to substantial differences in translocation dynamics in three dimensions. We show that the single-binding mode leads to dynamics that is very much like that in the constant-force driven translocation and accordingly mainly determined by tension propagation on the cis side. We obtain $\\beta \\approx 1.26$ for the exponent for the scaling of the translocation time with polymer length. This fairly low value can be ...

  6. The flexibility of flexicurity

    DEFF Research Database (Denmark)

    Jensen, Carsten Strøby

    2011-01-01

    by a special relation between flexibility, social security and active labour market policy, where a high level of social security is seen as a precondition for a labour market characterized by flexibility. In this article it is argued that the Danish labour market is characterized by having not just one model...... of flexicurity, but two. These two models cover different parts of the labour market and different segments of employees. The first model (the blue-collar flexicurity model) – the one that is often focused on in the literature – covers primarily skilled and unskilled workers on the labour market. The second...

  7. Secondary Structure Preferences of Mn2+ Binding Sites in Bacterial Proteins

    Directory of Open Access Journals (Sweden)

    Tatyana Aleksandrovna Khrustaleva

    2014-01-01

    Full Text Available 3D structures of proteins with coordinated Mn2+ ions from bacteria with low, average, and high genomic GC-content have been analyzed (149 PDB files were used. Major Mn2+ binders are aspartic acid (6.82% of Asp residues, histidine (14.76% of His residues, and glutamic acid (3.51% of Glu residues. We found out that the motif of secondary structure “beta strand-major binder-random coil” is overrepresented around all the three major Mn2+ binders. That motif may be followed by either alpha helix or beta strand. Beta strands near Mn2+ binding residues should be stable because they are enriched by such beta formers as valine and isoleucine, as well as by specific combinations of hydrophobic and hydrophilic amino acid residues characteristic to beta sheet. In the group of proteins from GC-rich bacteria glutamic acid residues situated in alpha helices frequently coordinate Mn2+ ions, probably, because of the decrease of Lys usage under the influence of mutational GC-pressure. On the other hand, the percentage of Mn2+ sites with at least one amino acid in the “beta strand-major binder-random coil” motif of secondary structure (77.88% does not depend on genomic GC-content.

  8. Relevance of DNA binding to the mechanism of anti-herpesvirus activity of benzhydrazone.

    Science.gov (United States)

    Palu, G; Tognon, M; Romanelli, M G; Rassu, M; Parolin, M C; Zagotto, G; Palumbo, M

    1993-04-01

    Benzhydrazone (1H-benz(f)indene-1,3(2H)-dione bis (amidino-hydrazone) (BH) is a synthetic compound with selective anti-herpesvirus activity. Its selectivity seems to stem from the inhibition of viral protein glycosylation and several hypotheses have been formulated to explain such an effect. Data presented here demonstrate that DNA binding is a prominent feature of BH. Interaction is taking place with a relatively high affinity constant and is more efficient for GC-rich viral sequences. Experiments with the cloned DNA fragments from a BH-resistant virus strain indicate that BH-DNA complex formation is drastically reduced as compared to BH-sensitive virus. The occurrence of the resistant phenotype in HEp-2 cells but not in Vero cells could be explained by differences in BH cytotoxicity. Changes in drug uptake and accumulation by cells following infection, in addition to GC preference, may also account for the degree of antiviral selectivity shown by BH. PMID:8387259

  9. Flexible Mental Calculation.

    Science.gov (United States)

    Threlfall, John

    2002-01-01

    Suggests that strategy choice is a misleading characterization of efficient mental calculation and that teaching mental calculation methods as a whole is not conducive to flexibility. Proposes an alternative in which calculation is thought of as an interaction between noticing and knowledge. Presents an associated teaching approach to promote…

  10. Flexible energy systems

    DEFF Research Database (Denmark)

    Lund, Henrik

    2003-01-01

    The paper discusses and analyses diffent national strategies and points out key changes in the energy system in order to achieve a system which can benefit from a high percentage of wind and CHP without having surplus production problems, introduced here as a flexible energy system....

  11. Flexible metal bellows

    CERN Multimedia

    1975-01-01

    A set of flexible metal bellows being fatigue-tested by repeated offset motion. Such bellows assemblies were used in the SPS vacuum system at places where , for instance, beam stoppers and collimators had to be moved frequently in and out of the beam path.

  12. Flexible Language Interoperability

    DEFF Research Database (Denmark)

    Ekman, Torbjörn; Mechlenborg, Peter; Schultz, Ulrik Pagh

    2007-01-01

    of the language. In this paper, we present a highly flexible yet efficient approach to hosting multiple programming languages on an object-oriented virtual machine. Our approach is based on extending the interface of each class with language-specific wrapper methods, offering each language a tailored view...

  13. Proto-oncogene FBI-1 (Pokemon/ZBTB7A) represses transcription of the tumor suppressor Rb gene via binding competition with Sp1 and recruitment of co-repressors.

    Science.gov (United States)

    Jeon, Bu-Nam; Yoo, Jung-Yoon; Choi, Won-Il; Lee, Choong-Eun; Yoon, Ho-Geun; Hur, Man-Wook

    2008-11-28

    FBI-1 (also called Pokemon/ZBTB7A) is a BTB/POZ-domain Krüppel-like zinc-finger transcription factor. Recently, FBI-1 was characterized as a proto-oncogenic protein, which represses tumor suppressor ARF gene transcription. The expression of FBI-1 is increased in many cancer tissues. We found that FBI-1 potently represses transcription of the Rb gene, a tumor suppressor gene important in cell cycle arrest. FBI-1 binds to four GC-rich promoter elements (FREs) located at bp -308 to -188 of the Rb promoter region. The Rb promoter also contains two Sp1 binding sites: GC-box 1 (bp -65 to -56) and GC-box 2 (bp -18 to -9), the latter of which is also bound by FBI-1. We found that FRE3 (bp -244 to -236) is also a Sp1 binding element. FBI-1 represses transcription of the Rb gene not only by binding to the FREs, but also by competing with Sp1 at the GC-box 2 and the FRE3. By binding to the FREs and/or the GC-box, FBI-1 represses transcription of the Rb gene through its POZ-domain, which recruits a co-repressor-histone deacetylase complex and deacetylates histones H3 and H4 at the Rb gene promoter. FBI-1 inhibits C2C12 myoblast cell differentiation by repressing Rb gene expression. PMID:18801742

  14. Cloning and characterization of a novel PE_PGRS60 protein (Rv3652) of Mycobacterium tuberculosis H37 Rv exhibit fibronectin-binding property.

    Science.gov (United States)

    Meena, Laxman S; Meena, Jaishree

    2016-07-01

    The binding of pathogenic bacteria to extracellular matrix components enhances adhesion and invasion of host cells. The host receptor proteins such as fibronectin (Fn) targeted to pathogenic ligands that have clinical importance. In the present study, we cloned, expressed, purified, and identified a novel Fn-binding protein from PE_PGRS60 (Rv3652) of Mycobacterium tuberculosis H37 Rv. The protein product of Rv3652 showed optimum binding efficiency to 10 ng Fn at 0.2 µg purified protein of PE_PGRS60 and 20 ng Fn at 0.2 µg concentrations, respectively. PE_PGRS60 protein (primary sequences) of different pathogenic mycobacterium species retrieved from NCBI exhibited complete homology at the 104 residues on multiple sequence alignment. The primary sequence of protein from H37 Rv was further used to predict cleavage signals. The secondary structure prediction method revealed a number of residues responsible for alpha helices formation and percentage of residues participating in the random coils and extended strands. In addition, online prediction tools such as B- and T-cell epitopes showed the surface probability scale and antigenic propensity scale. The current finding opens new opportunity to mycobacterial survival and pathogenesis research of PE-polymorphic GC-rich repetitive sequences (PE-PGRS) family proteins.

  15. FLEXIBLE GEIGER COUNTER

    Science.gov (United States)

    Richter, H.G.; Gillespie, A.S. Jr.

    1963-11-12

    A flexible Geiger counter constructed from materials composed of vinyl chloride polymerized with plasticizers or co-polymers is presented. The counter can be made either by attaching short segments of corrugated plastic sleeving together, or by starting with a length of vacuum cleaner hose composed of the above materials. The anode is maintained substantially axial Within the sleeving or hose during tube flexing by means of polystyrene spacer disks or an easily assembled polyethylene flexible cage assembly. The cathode is a wire spiraled on the outside of the counter. The sleeving or hose is fitted with glass end-pieces or any other good insulator to maintain the anode wire taut and to admit a counting gas mixture into the counter. Having the cathode wire on the outside of the counter substantially eliminates the objectional sheath effect of prior counters and permits counting rates up to 300,000 counts per minute. (AEC)

  16. Control of flexible structures

    Science.gov (United States)

    Russell, R. A.

    1985-01-01

    The requirements for future space missions indicate that many of these spacecraft will be large, flexible, and in some applications, require precision geometries. A technology program that addresses the issues associated with the structure/control interactions for these classes of spacecraft is discussed. The goal of the NASA control of flexible structures technology program is to generate a technology data base that will provide the designer with options and approaches to achieve spacecraft performance such as maintaining geometry and/or suppressing undesired spacecraft dynamics. This technology program will define the appropriate combination of analysis, ground testing, and flight testing required to validate the structural/controls analysis and design tools. This work was motivated by a recognition that large minimum weight space structures will be required for many future missions. The tools necessary to support such design included: (1) improved structural analysis; (2) modern control theory; (3) advanced modeling techniques; (4) system identification; and (5) the integration of structures and controls.

  17. Flexible rotor dynamics analysis

    Science.gov (United States)

    Shen, F. A.

    1973-01-01

    A digital computer program was developed to analyze the general nonaxisymmetric and nonsynchronous transient and steady-state rotor dynamic performance of a bending- and shear-wise flexible rotor-bearing system under various operating conditions. The effects of rotor material mechanical hysteresis, rotor torsion flexibility, transverse effects of rotor axial and torsional loading and the anisotropic, in-phase and out-of-phase bearing stiffness and damping force and moment coefficients were included in the program to broaden its capability. An optimum solution method was found and incorporated in the computer program. Computer simulation of experimental data was made and qualitative agreements observed. The mathematical formulations, computer program verification, test data simulation, and user instruction was presented and discussed.

  18. Flexible Laser Metal Cutting

    DEFF Research Database (Denmark)

    Villumsen, Sigurd; Jørgensen, Steffen Nordahl; Kristiansen, Morten

    2014-01-01

    This paper describes a new flexible and fast approach to laser cutting called ROBOCUT. Combined with CAD/CAM technology, laser cutting of metal provides the flexibility to perform one-of-a-kind cutting and hereby realises mass production of customised products. Today’s laser cutting techniques...... possess, despite their wide use in industry, limitations regarding speed and geometry. Research trends point towards remote laser cutting techniques which can improve speed and geometrical freedom and hereby the competitiveness of laser cutting compared to fixed-tool-based cutting technology...... such as punching. This paper presents the concepts and preliminary test results of the ROBOCUT laser cutting technology, a technology which potentially can revolutionise laser cutting....

  19. Diffusion in flexible pipes

    Energy Technology Data Exchange (ETDEWEB)

    Brogaard Kristensen, S.

    2000-06-01

    This report describes the work done on modelling and simulation of the complex diffusion of gas through the wall of a flexible pipe. The diffusion and thus the pressure in annulus depends strongly on the diffusion and solubility parameters of the gas-polymer system and on the degree of blocking of the outer surface of the inner liner due to pressure reinforcements. The report evaluates the basis modelling required to describe the complex geometries and flow patterns. Qualitatively results of temperature and concentration profiles are shown in the report. For the program to serve any modelling purpose in 'real life' the results need to be validated and possibly the model needs corrections. Hopefully, a full-scale test of a flexible pipe will provide the required temperatures and pressures in annulus to validate the models. (EHS)

  20. More flexibility for DESY

    CERN Multimedia

    2003-01-01

    In the future, budgeting at DESY will be more efficient. The 16 associated research centers are to be granted a wider margin in matters of finance and human resources. The Budget Committee of the German Bundestag has agreed to abstain from mandatory staff appointments. The current pre-determined "job pyramid" will be replaced by a more flexible mechanism, so that the conclusion of fixed labor contracts can more closely follow the needs of research (1 page).

  1. Industrial Fuel Flexibility Workshop

    Energy Technology Data Exchange (ETDEWEB)

    none,

    2006-09-01

    On September 28, 2006, in Washington, DC, ITP and Booz Allen Hamilton conducted a fuel flexibility workshop with attendance from various stakeholder groups. Workshop participants included representatives from the petrochemical, refining, food and beverage, steel and metals, pulp and paper, cement and glass manufacturing industries; as well as representatives from industrial boiler manufacturers, technology providers, energy and waste service providers, the federal government and national laboratories, and developers and financiers.

  2. Flexible Word Classes

    DEFF Research Database (Denmark)

    van Lier, Eva; Rijkhoff, Jan

    2013-01-01

    • First major publication on the phenomenon • Offers cross-linguistic, descriptive, and diverse theoretical approaches • Includes analysis of data from different language families and from lesser studied languages This book is the first major cross-linguistic study of 'flexible words', i.e. words...... Indonesian, Santali, Sri Lanka Malay, Lushootseed, Gooniyandi, and Late Archaic Chinese. Readership: Linguists and students of linguistics and cognitive sciences, anthropologists, philosophers...

  3. Flexible Land Administration

    DEFF Research Database (Denmark)

    Enemark, Stig

    2014-01-01

    Security of tenure is widely considered to be the missing piece of the puzzle when it comes to eradication of poverty. And, as explained in the previous issue of Geoinformatics, the European Union is now placing land rights at the heart of EU development policy. This article presents a way forwar...... in terms of building flexible and "fit-for-purpose" land administration systems in developing countries. This will ensure security of tenure for all and sustainable management of the use of land....

  4. Measuring process flexibility and agility

    NARCIS (Netherlands)

    Gong, Y.; Janssen, M.

    2010-01-01

    In their attempt to improve their systems and architectures, organizations need to be aware of the types of flexibility and agility and the current level of each type of flexibility and agility. Flexibility is the general ability to react to changes, whilst agility is the speed in responding to vari

  5. Flexible Scheduling: Making the Transition

    Science.gov (United States)

    Creighton, Peggy Milam

    2008-01-01

    Citing literature that supports the benefits of flexible scheduling on student achievement, the author exhorts readers to campaign for flexible scheduling in their library media centers. She suggests tips drawn from the work of Graziano (2002), McGregor (2006) and Stripling (1997) for making a smooth transition from fixed to flexible scheduling:…

  6. Designing structural supply chain flexibility

    NARCIS (Netherlands)

    Mulinski, Ksawery Jan

    2012-01-01

    In a continuously changing business environment the role of supply chain flexibility is constantly increasing. A flexible supply chain can ensure survival in quickly changing market conditions as well as enable sustainable growth. This thesis explores the topic of supply chain flexibility with focus

  7. Construction and Validation of the Rhodobacter sphaeroides 2.4.1 DNA Microarray: Transcriptome Flexibility at Diverse Growth Modes

    Energy Technology Data Exchange (ETDEWEB)

    Pappas, Christopher T. [University of Wyoming, Laramie; Sram, Jakub [University of Wyoming, Laramie; Moskvin, Oleg V. [University of Wyoming, Laramie; Ivanov, Pavel S. [University of Wyoming, Laramie; Mackenzie, Christopher [University of Texas; Choudhary, Madhusudan [University of Texas; Land, Miriam L [ORNL; Larimer, Frank W [ORNL; Kaplan, Samuel [ORNL; Gomelsky, Mark [University of Wyoming, Laramie

    2004-07-01

    A high-density oligonucleotide DNA microarray, a genechip, representing the 4.6-Mb genome of the facultative phototrophic proteobacterium, Rhodobacter sphaeroides 2.4.1, was custom-designed and manufactured by Affymetrix, Santa Clara, Calif. The genechip contains probe sets for 4,292 open reading frames (ORFs), 47 rRNA and tRNA genes, and 394 intergenic regions. The probe set sequences were derived from the genome annotation generated by Oak Ridge National Laboratory after extensive revision, which was based primarily upon codon usage characteristic of this GC-rich bacterium. As a result of the revision, numerous missing ORFs were uncovered, nonexistent ORFs were deleted, and misidentified start codons were corrected. To evaluate R. sphaeroides transcriptome flexibility, expression profiles for three diverse growth modes-aerobic respiration, anaerobic respiration in the dark, and anaerobic photosynthesis-were generated. Expression levels of one-fifth to one-third of the R. sphaeroides ORFs were significantly different in cells under any two growth modes. Pathways involved in energy generation and redox balance maintenance under three growth modes were reconstructed. Expression patterns of genes involved in these pathways mirrored known functional changes, suggesting that massive changes in gene expression are the major means used by R. sphaeroides in adaptation to diverse conditions. Differential expression was observed for genes encoding putative new participants in these pathways (additional photosystem genes, duplicate NADH dehydrogenase, ATP synthases), whose functionality has yet to be investigated. The DNA microarray data correlated well with data derived from quantitative reverse transcription-PCR, as well as with data from the literature, thus validating the R. sphaeroides genechip as a powerful and reliable tool for studying unprecedented metabolic versatility of this bacterium.

  8. Global Analysis of Flexible Risers

    DEFF Research Database (Denmark)

    Banke, Lars

    1996-01-01

    Flexible pipes are often a technically attractive alternative to the traditional steel pipe. Often commercial utilisation of oil/gas fields depends on the use of flexible pipes. An example is when floating production vessels are used, where the flexible pipe follows the wave induced motions...... and thus resists the loading from the environment in a more suitable way.A flexible pipe is a composite structure, built up of several layers each having a specific function. Due to the flexibility, the response of the pipe in wave induced motions are governed by a complex hydroelastic set of differential...... equations.An important part in the design of flexible pipes is the end fitting. The purpose of the end fitting is mainly to connect pipe units, but it also combines and terminates the different layers of the flexible pipe. The end fitting system contains a bending stiffener and an end fitting. The bending...

  9. Flexible composite radiation detector

    Science.gov (United States)

    Cooke, D. Wayne; Bennett, Bryan L.; Muenchausen, Ross E.; Wrobleski, Debra A.; Orler, Edward B.

    2006-12-05

    A flexible composite scintillator was prepared by mixing fast, bright, dense rare-earth doped powdered oxyorthosilicate (such as LSO:Ce, LSO:Sm, and GSO:Ce) scintillator with a polymer binder. The binder is transparent to the scintillator emission. The composite is seamless and can be made large and in a wide variety of shapes. Importantly, the composite can be tailored to emit light in a spectral region that matches the optimum response of photomultipliers (about 400 nanometers) or photodiodes (about 600 nanometers), which maximizes the overall detector efficiency.

  10. Rotating flexible drag mill

    Science.gov (United States)

    Pepper, W.B.

    1984-05-09

    A rotating parachute for decelerating objects travelling through atmosphere at subsonic or supersonic deployment speeds includes a circular canopy having a plurality of circumferentially arranged flexible panels projecting radially from a solid central disk. A slot extends radially between adjacent panels to the outer periphery of the canopy. Upon deployment, the solid disk diverts air radially to rapidly inflate the panels into a position of maximum diameter. Air impinging on the panels adjacent the panel slots rotates the parachute during its descent. Centrifugal force flattens the canopy into a constant maximum diameter during terminal descent for maximum drag and deceleration.

  11. Flexible Volumetric Structure

    Science.gov (United States)

    Cagle, Christopher M. (Inventor); Schlecht, Robin W. (Inventor)

    2014-01-01

    A flexible volumetric structure has a first spring that defines a three-dimensional volume and includes a serpentine structure elongatable and compressible along a length thereof. A second spring is coupled to at least one outboard edge region of the first spring. The second spring is a sheet-like structure capable of elongation along an in-plane dimension thereof. The second spring is oriented such that its in-plane dimension is aligned with the length of the first spring's serpentine structure.

  12. Flexible ocean upwelling pipe

    Science.gov (United States)

    Person, Abraham

    1980-01-01

    In an ocean thermal energy conversion facility, a cold water riser pipe is releasably supported at its upper end by the hull of the floating facility. The pipe is substantially vertical and has its lower end far below the hull above the ocean floor. The pipe is defined essentially entirely of a material which has a modulus of elasticity substantially less than that of steel, e.g., high density polyethylene, so that the pipe is flexible and compliant to rather than resistant to applied bending moments. The position of the lower end of the pipe relative to the hull is stabilized by a weight suspended below the lower end of the pipe on a flexible line. The pipe, apart from the weight, is positively buoyant. If support of the upper end of the pipe is released, the pipe sinks to the ocean floor, but is not damaged as the length of the line between the pipe and the weight is sufficient to allow the buoyant pipe to come to a stop within the line length after the weight contacts the ocean floor, and thereafter to float submerged above the ocean floor while moored to the ocean floor by the weight. The upper end of the pipe, while supported by the hull, communicates to a sump in the hull in which the water level is maintained below the ambient water level. The sump volume is sufficient to keep the pipe full during heaving of the hull, thereby preventing collapse of the pipe.

  13. Asymmetric Flexible Supercapacitor Stack

    Directory of Open Access Journals (Sweden)

    Leela Mohana Reddy A

    2008-01-01

    Full Text Available AbstractElectrical double layer supercapacitor is very significant in the field of electrical energy storage which can be the solution for the current revolution in the electronic devices like mobile phones, camera flashes which needs flexible and miniaturized energy storage device with all non-aqueous components. The multiwalled carbon nanotubes (MWNTs have been synthesized by catalytic chemical vapor deposition technique over hydrogen decrepitated Mischmetal (Mm based AB3alloy hydride. The polymer dispersed MWNTs have been obtained by insitu polymerization and the metal oxide/MWNTs were synthesized by sol-gel method. Morphological characterizations of polymer dispersed MWNTs have been carried out using scanning electron microscopy (SEM, transmission electron microscopy (TEM and HRTEM. An assymetric double supercapacitor stack has been fabricated using polymer/MWNTs and metal oxide/MWNTs coated over flexible carbon fabric as electrodes and nafion®membrane as a solid electrolyte. Electrochemical performance of the supercapacitor stack has been investigated using cyclic voltammetry, galvanostatic charge-discharge, and electrochemical impedance spectroscopy.

  14. In Silico Investigation of the Neurotensin Receptor 1 Binding Site

    DEFF Research Database (Denmark)

    Lückmann, Michael; Holst, Birgitte; Schwartz, Thue W.;

    2016-01-01

    the binding mode of SR48692 and other small mol. compds. to NTSR1, we applied an Automated Ligand-guided Backbone Ensemble Receptor Optimization protocol (ALiBERO), taking receptor flexibility and ligand knowledge into account. Structurally overlapping binding poses for SR48692 and NTS8-13 were obsd., despite...

  15. Rational design, synthesis, and DNA binding properties of novel sequence-selective peptidyl congeners of ametantrone.

    Science.gov (United States)

    Gianoncelli, Alessandra; Basili, Serena; Scalabrin, Matteo; Sosic, Alice; Moro, Stefano; Zagotto, Giuseppe; Palumbo, Manlio; Gresh, Nohad; Gatto, Barbara

    2010-07-01

    Natural and synthetic compounds characterized by an anthraquinone nucleus represent an important class of anti-neoplastic agents, the mechanism of action of which is related to intercalation into DNA. Ametantrone (AM) is a synthetic 9,10-anthracenedione bearing two (hydroxyethylamino)ethylamino residues at positions 1 and 4; along with other anthraquinones and anthracyclines, it shares a polycyclic intercalating moiety and charged side chains that stabilize DNA binding. All these drugs elicit adverse side effects, which represent a challenge for antitumor chemotherapy. In the present work the structure of AM was augmented with appropriate groups that target well-defined base pairs in the major groove. These should endow AM with DNA sequence selectivity. We describe the rationale for the synthesis and the evaluation of activity of a new series of compounds in which the planar anthraquinone is conjugated at positions 1 and 4 through the side chains of AM or other bioisosteric linkers to appropriate dipeptides. The designed novel AM derivatives were shown to selectively stabilize two oligonucleotide duplexes that both have a palindromic GC-rich hexanucleotide core, but their stabilizing effects on a random DNA sequence was negligible. In the case of the most effective compound, the 1,4-bis-[Gly-(L-Lys)] derivative of AM, the experimental results confirm the predictions of earlier theoretical computations. In contrast, AM had equal stabilizing effects on all three sequences and showed no preferential binding. This novel peptide derivative can be classified as a strong binder regarding the sequences that it selectively targets, possibly opening the exploitation of less cytotoxic conjugates of AM to the targeted treatment of oncological and viral diseases. PMID:20458714

  16. Aggregating and Disaggregating Flexibility Objects

    DEFF Research Database (Denmark)

    Siksnys, Laurynas; Valsomatzis, Emmanouil; Hose, Katja;

    2015-01-01

    In many scientific and commercial domains we encounter flexibility objects, i.e., objects with explicit flexibilities in a time and an amount dimension (e.g., energy or product amount). Applications of flexibility objects require novel and efficient techniques capable of handling large amounts...... of such objects while preserving flexibility. Hence, this paper formally defines the concept of flexibility objects (flex-objects) and provides a novel and efficient solution for aggregating and disaggregating flex-objects. Out of the broad range of possible applications, this paper will focus on smart grid...... energy data management and discuss strategies for aggregation and disaggregation of flex-objects while retaining flexibility. This paper further extends these approaches beyond flex-objects originating from energy consumption by additionally considering flex-objects originating from energy production...

  17. Conformational flexibility of aspartame.

    Science.gov (United States)

    Toniolo, Claudio; Temussi, Pierandrea

    2016-05-01

    L-Aspartyl-L-phenylalanine methyl ester, better known as aspartame, is not only one of the most used artificial sweeteners, but also a very interesting molecule with respect to the correlation between molecular structure and taste. The extreme conformational flexibility of this dipeptide posed a huge difficulty when researchers tried to use it as a lead compound to design new sweeteners. In particular, it was difficult to take advantage of its molecular model as a mold to infer the shape of the, then unknown, active site of the sweet taste receptor. Here, we follow the story of the 3D structural aspects of aspartame from early conformational studies to recent docking into homology models of the receptor. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 376-384, 2016. PMID:27038223

  18. Flexible retinal electrode array

    Energy Technology Data Exchange (ETDEWEB)

    Okandan, Murat (Albuquerque, NM); Wessendorf, Kurt O. (Albuquerque, NM); Christenson, Todd R. (Albuquerque, NM)

    2006-10-24

    An electrode array which has applications for neural stimulation and sensing. The electrode array can include a large number of electrodes each of which is flexibly attached to a common substrate using a plurality of springs to allow the electrodes to move independently. The electrode array can be formed from a combination of bulk and surface micromachining, with electrode tips that can include an electroplated metal (e.g. platinum, iridium, gold or titanium) or a metal oxide (e.g. iridium oxide) for biocompatibility. The electrode array can be used to form a part of a neural prosthesis, and is particularly well adapted for use in an implantable retinal prosthesis where the electrodes can be tailored to provide a uniform gentle contact pressure with optional sensing of this contact pressure at one or more of the electrodes.

  19. Flexible Query Answering Systems

    DEFF Research Database (Denmark)

    This book constitutes the refereed proceedings of the 10th International Conference on Flexible Query Answering Systems, FQAS 2013, held in Granada, Spain, in September 2013. The 59 full papers included in this volume were carefully reviewed and selected from numerous submissions. The papers...... are organized in a general session train and a parallel special session track. The general session train covers the following topics: querying-answering systems; semantic technology; patterns and classification; personalization and recommender systems; searching and ranking; and Web and human......-computer interaction. The special track covers some some specific and, typically, newer fields, namely: environmental scanning for strategic early warning; generating linguistic descriptions of data; advances in fuzzy querying and fuzzy databases: theory and applications; fusion and ensemble techniques for on-line...

  20. Teacher Flexibility in Mathematical Discussion

    Science.gov (United States)

    Leikin, Roza; Dinur, Sariga

    2007-01-01

    The significance of discussion in mathematics classes has been prominently debated in the research literature. Different studies have stressed the importance of teacher flexibility in orchestrating the discussion. We introduce an operational definition of teacher flexibility. In a case study with one secondary-school mathematics teacher, we…

  1. On flexible and rigid nouns

    DEFF Research Database (Denmark)

    Rijkhoff, Jan

    2008-01-01

    , Non-Verb, Modifier), there are also flexible word classes within the rigid lexical category Noun (Set Noun, Sort Noun, General Noun). Members of flexible word classes are characterized by their vague semantics, which in the case of nouns means that values for the semantic features Shape...

  2. On flexible and rigid nouns

    DEFF Research Database (Denmark)

    Rijkhoff, Jan

    2010-01-01

    This article argues that in addition to the major flexible lexical categories in Hengeveld’s classification of parts of speech systems (Contentive, Non-Verb, Modifier), there are also flexible word classes within the rigid lexical category Noun (Set Noun, Sort Noun, General Noun). Members...

  3. Flexible Stamp for Nanoimprint Lithography

    DEFF Research Database (Denmark)

    Nielsen, Theodor; Pedersen, Rasmus H.; Hansen, Ole;

    2005-01-01

    The design, fabrication and performance of a flexible silicon stamp for homogenous large area nanoimprint lithography (NIL) are presented. The flexible stamp is fabricated by bulk semiconductor micro machining of a 4-inch silicon wafer and consists of thick anchor like imprint areas connected...

  4. Sensor Technologies on Flexible Substrates

    Science.gov (United States)

    Koehne, Jessica

    2016-01-01

    NASA Ames has developed sensor technologies on flexible substrates integrated into textiles for personalized environment monitoring and human performance evaluation. Current technologies include chemical sensing for gas leak and event monitoring and biological sensors for human health and performance monitoring. Targeted integration include next generation EVA suits and flexible habitats.

  5. Building Highly Flexible Polyelectrolyte Nanotubes

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    @@ Flexibility of polyelectrolyte nanotubes is necessary if they are to be exploited in applications such as developing photoelectric devices with strong mechanical properties. In a recent attempt, high flexibility has been observed from such nanotubes prepared by a research team headed by Prof. Li Junbai of the CAS Institute of Chemistry (ICCAS).

  6. Promoter analysis of intestinal genes induced during iron-deprivation reveals enrichment of conserved SP1-like binding sites

    Directory of Open Access Journals (Sweden)

    Hu Zihua

    2007-11-01

    Full Text Available Abstract Background Iron-deficiency leads to the induction of genes related to intestinal iron absorption and homeostasis. By analyzing a large GeneChip® dataset from the rat intestine, we identified a large cluster of 228 genes that was induced by iron-deprivation. Only 2 of these genes contained 3' iron-response elements, suggesting that other regulation including transcriptional may be involved. We therefore utilized computational methods to test the hypothesis that some of the genes within this large up-regulated cluster are co-ordinately regulated by common transcriptional mechanisms. We thus identified promoters from the up-regulated gene cluster from rat, mouse and human, and performed enrichment analyses with the Clover program and the TRANSFAC database. Results Surprisingly, we found a strong statistical enrichment for SP1 binding sites in our experimental promoters as compared to background sequences. As the TRANSFAC database cannot distinguish among SP/KLF family members, many of which bind similar GC-rich DNA sequences, we surmise that SP1 or an SP1-like factor could be involved in this response. In fact, we detected induction of SP6/KLF14 in the GeneChip® studies, and confirmed it by real-time PCR. Additional computational analyses suggested that an SP1-like factor may function synergistically with a FOX TF to regulate a subset of these genes. Furthermore, analysis of promoter sequences identified many genes with multiple, conserved SP1 and FOX binding sites, the relative location of which within orthologous promoters was highly conserved. Conclusion SP1 or a closely related factor may play a primary role in the genetic response to iron-deficiency in the mammalian intestine.

  7. Orthogonal flexible Rydberg aggregates

    CERN Document Server

    Leonhardt, K; Rost, J M

    2015-01-01

    We study the link between atomic motion and exciton transport in flexible Rydberg aggregates, assemblies of highly excited light alkali atoms, for which motion due to dipole-dipole interaction becomes relevant. In two one-dimensional atom chains crossing at a right angle adiabatic exciton transport is affected by a conical intersection of excitonic energy surfaces, which induces controllable non-adiabatic effects. A joint exciton/motion pulse that is initially governed by a single energy surface is coherently split into two modes after crossing the intersection. The modes induce strongly different atomic motion, leading to clear signatures of non-adiabatic effects in atomic density profiles. We have shown how this scenario can be exploited as an exciton switch, controlling direction and coherence properties of the joint pulse on the second of the chains [K.~Leonhardt {\\it et al.}, Phys.~Rev.~Lett. {\\bf 113} 223001 (2014)]. In this article we discuss the underlying complex dynamics in detail, characterise the ...

  8. Flexible Computational Science Infrastructure

    Energy Technology Data Exchange (ETDEWEB)

    2016-04-06

    FleCSI is a compile-time configurable framework designed to support multi-physics application development. As such, FleCSI attempts to provide a very general set of infrastructure design patterns that can be specialized and extended to suit the needs of a broad variety of solver and data requirements. Current support includes multi-dimensional mesh topology, mesh geometry, and mesh adjacency information, n-dimensional hashed-tree data structures, graph partitioning interfaces, and dependency closures. FleCSI also introduces a functional programming model with control, execution, and data abstractions that are consistent with both MPI and state-of-the-art task-based runtimes such as Legion and Charm++. The FleCSI abstraction layer provides the developer with insulation from the underlying runtime, while allowing support for multiple runtime systems, including conventional models like asynchronous MPI. The intent is to give developers a concrete set of user-friendly programming tools that can be used now, while allowing flexibility in choosing runtime implementations and optimizations that can be applied to architectures and runtimes that arise in the future. The control and execution models in FleCSI also provide formal nomenclature for describing poorly understood concepts like kernels and tasks.

  9. Flexible Foot Test Assembly

    Energy Technology Data Exchange (ETDEWEB)

    Kurita, C.H.; /Fermilab

    1987-04-27

    A test model of the flexible foot support was constructed early in the design stages to check its reactions to applied loads. The prototype was made of SS 304 and contained four vertical plates as opposed to the fourteen Inconel 718 plates which comprise the actual structure. Due to the fact that the prototype was built before the design of the support was finalized, the plate dimensions are different from those of the actual proposed design (i.e. model plate thickness is approximately one-half that of the actual plates). See DWG. 3740.210-MC-222376 for assembly details of the test model and DWG. 3740.210-MB-222377 for plate dimensions. This stanchion will be required to not only support the load of the inner vessel of the cryostat and its contents, but it must also allow for the movement of the vessel due to thermal contraction. Assuming that each vertical plate acts as a column, then the following formula from the Manual of Steel Construction (American Institute of Steel Construction, Inc., Eigth edition, 1980) can be applied to determine whether or not such columns undergoing simultaneous axial compression and transverse loading are considered safe for the given loading. The first term is representative of the axially compressive stress, and the second term, the bending stress. If the actual compressive stress is greater than 15% of the allowable compressive stress, then there are additional considerations which must be accounted for in the bending stress term.

  10. Metabolic flexibility and insulin resistance.

    Science.gov (United States)

    Galgani, Jose E; Moro, Cedric; Ravussin, Eric

    2008-11-01

    Metabolic flexibility is the capacity for the organism to adapt fuel oxidation to fuel availability. The inability to modify fuel oxidation in response to changes in nutrient availability has been implicated in the accumulation of intramyocellular lipid and insulin resistance. The metabolic flexibility assessed by the ability to switch from fat to carbohydrate oxidation is usually impaired during a hyperinsulinemic clamp in insulin-resistant subjects; however, this "metabolic inflexibility" is mostly the consequence of impaired cellular glucose uptake. Indeed, after controlling for insulin-stimulated glucose disposal rate (amount of glucose available for oxidation), metabolic flexibility is not altered in obesity regardless of the presence of type 2 diabetes. To understand how intramyocellular lipids accumulate and cause insulin resistance, the assessment of metabolic flexibility to high-fat diets is more relevant than metabolic flexibility during a hyperinsulinemic clamp. An impaired capacity to upregulate muscle lipid oxidation in the face of high lipid supply may lead to increased muscle fat accumulation and insulin resistance. Surprisingly, very few studies have investigated the response to high-fat diets. In this review, we discuss the role of glucose disposal rate, adipose tissue lipid storage, and mitochondrial function on metabolic flexibility. Additionally, we emphasize the bias of using the change in respiratory quotient to calculate metabolic flexibility and propose novel approaches to assess metabolic flexibility. On the basis of current evidence, one cannot conclude that impaired metabolic flexibility is responsible for the accumulation of intramyocellular lipid and insulin resistance. We propose to study metabolic flexibility in response to high-fat diets in individuals having contrasting degree of insulin sensitivity and/or mitochondrial characteristics. PMID:18765680

  11. Multifunctional, flexible electronic systems based on engineered nanostructured materials

    Science.gov (United States)

    Ko, Hyunhyub; Kapadia, Rehan; Takei, Kuniharu; Takahashi, Toshitake; Zhang, Xiaobo; Javey, Ali

    2012-08-01

    The development of flexible electronic systems has been extensively researched in recent years, with the goal of expanding the potential scope and market of modern electronic devices in the areas of computation, communications, displays, sensing and energy. Uniquely, the use of soft polymeric substrates enables the incorporation of advanced features beyond mechanical bendability and stretchability. In this paper, we describe several functionalities which can be achieved using engineered nanostructured materials. In particular, reversible binding, self-cleaning, antireflective and shape-reconfigurable properties are introduced for the realization of multifunctional, flexible electronic devices. Examples of flexible systems capable of spatial mapping and/or responding to external stimuli are also presented as a new class of user-interactive devices.

  12. Probabilistic Model to Treat Flexibility in Molecular Contacts

    OpenAIRE

    Hakulinen, Riku; Puranen, Santeri

    2016-01-01

    Evaluating accessible conformational space is computationally expensive and thermal motions are partly neglected in computer models of molecular interactions. This produces error into the estimates of binding strength. We introduce a method for modelling interactions so that structural flexibility is inherently taken into account. It has a statistical model for 3D properties of 'nonlocal' contacts and a physics based description of 'local' interactions, based on mechanical torque. The form of...

  13. Flexible armored blanket development

    Energy Technology Data Exchange (ETDEWEB)

    Roth, E.S.

    1978-05-01

    An exploratory development contract was undertaken on December 23, 1977 which had as its purpose the development and demonstration of a flexible armored blanket design suitable for providing ballistic protection to nuclear weapons during shipment. Objectives were to design and fabricate a prototype blanket which will conform to the weapon shape, is troop-handleable in the field, and which, singly or in multiple layers, can defeat a range of kinetic energy armor piercing (AP) ammunition potentially capable of damaging the critical portion of the nuclear weapon. Following empirical testing, including the firing of threat ammunition under controlled laboratory and field test conditions, materials were selected and assembled into two blanket designs, each weighing approximately 54 kg/m{sup 2} (11 lbs/ft{sup 2}) and estimated to cost from $111 to $180 per ft{sup 2} in production. A firing demonstration to evidence blanket performance against terrorist/light infantry weapons, heavy infantry weapons, and aircraft cannon was conducted for representatives of the DOD and interested Sandia employees on April 12, 1978. The blankets performed better than anticipated defeating bullets up to 7.62 mm x 51 mm AP with one layer and projectiles up to 23 mm HEI with two layers. Based on these preliminary tests it is recommended that development work be continued with the following objectives: (1) the selection by the DOD of priority applications, (2) the specific design and fabrication of sufficient quantities of armored blankets for field testing, (3) the evaluation of the blankets by DOD operational units, with reports to Sandia Laboratories to enable final design.

  14. Guideline Implementation: Processing Flexible Endoscopes.

    Science.gov (United States)

    Bashaw, Marie A

    2016-09-01

    The updated AORN "Guideline for processing flexible endoscopes" provides guidance to perioperative, endoscopy, and sterile processing personnel for processing all types of reusable flexible endoscopes and accessories in all procedural settings. This article focuses on key points of the guideline to help perioperative personnel safely and effectively process flexible endoscopes to prevent infection transmission. The key points address verification of manual cleaning, mechanical cleaning and processing, storage in a drying cabinet, determination of maximum storage time before reprocessing is needed, and considerations for implementing a microbiologic surveillance program. Perioperative RNs should review the complete guideline for additional information and for guidance when writing and updating policies and procedures.

  15. Guideline Implementation: Processing Flexible Endoscopes.

    Science.gov (United States)

    Bashaw, Marie A

    2016-09-01

    The updated AORN "Guideline for processing flexible endoscopes" provides guidance to perioperative, endoscopy, and sterile processing personnel for processing all types of reusable flexible endoscopes and accessories in all procedural settings. This article focuses on key points of the guideline to help perioperative personnel safely and effectively process flexible endoscopes to prevent infection transmission. The key points address verification of manual cleaning, mechanical cleaning and processing, storage in a drying cabinet, determination of maximum storage time before reprocessing is needed, and considerations for implementing a microbiologic surveillance program. Perioperative RNs should review the complete guideline for additional information and for guidance when writing and updating policies and procedures. PMID:27568535

  16. Flexible sensors for biomedical technology.

    Science.gov (United States)

    Vilela, Diana; Romeo, Agostino; Sánchez, Samuel

    2016-02-01

    Flexible sensing devices have gained a great deal of attention among the scientific community in recent years. The application of flexible sensors spans over several fields, including medicine, industrial automation, robotics, security, and human-machine interfacing. In particular, non-invasive health-monitoring devices are expected to play a key role in the improvement of patient life and in reducing costs associated with clinical and biomedical diagnostic procedures. Here, we focus on recent advances achieved in flexible devices applied on the human skin for biomedical and healthcare purposes. PMID:26675174

  17. Flexible sensors for biomedical technology.

    Science.gov (United States)

    Vilela, Diana; Romeo, Agostino; Sánchez, Samuel

    2016-02-01

    Flexible sensing devices have gained a great deal of attention among the scientific community in recent years. The application of flexible sensors spans over several fields, including medicine, industrial automation, robotics, security, and human-machine interfacing. In particular, non-invasive health-monitoring devices are expected to play a key role in the improvement of patient life and in reducing costs associated with clinical and biomedical diagnostic procedures. Here, we focus on recent advances achieved in flexible devices applied on the human skin for biomedical and healthcare purposes.

  18. Flexible Transparent Electronic Gas Sensors.

    Science.gov (United States)

    Wang, Ting; Guo, Yunlong; Wan, Pengbo; Zhang, Han; Chen, Xiaodong; Sun, Xiaoming

    2016-07-01

    Flexible and transparent electronic gas sensors capable of real-time, sensitive, and selective analysis at room-temperature, have gained immense popularity in recent years for their potential to be integrated into various smart wearable electronics and display devices. Here, recent advances in flexible transparent sensors constructed from semiconducting oxides, carbon materials, conducting polymers, and their nanocomposites are presented. The sensing material selection, sensor device construction, and sensing mechanism of flexible transparent sensors are discussed in detail. The critical challenges and future development associated with flexible and transparent electronic gas sensors are presented. Smart wearable gas sensors are believed to have great potential in environmental monitoring and noninvasive health monitoring based on disease biomarkers in exhaled gas.

  19. Analyzing binding data.

    Science.gov (United States)

    Motulsky, Harvey J; Neubig, Richard R

    2010-07-01

    Measuring the rate and extent of radioligand binding provides information on the number of binding sites, and their affinity and accessibility of these binding sites for various drugs. This unit explains how to design and analyze such experiments.

  20. FLEXIBLE FLATFOOT IN CHILDREN (REVIEW)

    OpenAIRE

    Владимир Маркович Кенис; Юрий Алексеевич Лапкин; Руслан Халилович Хусаинов; Андрей Викторович Сапоговский

    2014-01-01

    Flatfoot is one of the most common musculoskeletal conditions in the daily practice of pediatric orthopedists. Despite of numerous studies, diagnostic criteria and principles of management remain controversial. Flexible flatfoot - is visually detectable decrease in the height of the longitudinal arch of the foot, which can be spontaneously corrected by active or passive motion and not accompanied by any contracture of foot and ankle. Flexible flatfoot is a benign condition which is normal for...

  1. Determinants of flexible work arrangements

    OpenAIRE

    Sarbu, Miruna

    2014-01-01

    Flexible work arrangements such as allowing employees to work at home are used in firms, especially since information and communication technologies have become so widespread. Using individual-level data from 10,884 German employees, this paper analyses the determinants of working at home as a form of flexible work arrangements. The analysis is based on descriptive analyses and a discrete choice model using a probit estimation approach. The results reveal that men have a higher...

  2. Metabolic flexibility and insulin resistance

    OpenAIRE

    Galgani, Jose E.; Moro, Cedric; Ravussin, Eric

    2008-01-01

    Metabolic flexibility is the capacity for the organism to adapt fuel oxidation to fuel availability. The inability to modify fuel oxidation in response to changes in nutrient availability has been implicated in the accumulation of intramyocellular lipid and insulin resistance. The metabolic flexibility assessed by the ability to switch from fat to carbohydrate oxidation is usually impaired during a hyperinsulinemic clamp in insulin-resistant subjects; however, this “metabolic inflexibility” i...

  3. Time-Precision Flexible Adder

    OpenAIRE

    García Chamizo, Juan Manuel; Mora Pascual, Jerónimo Manuel; Mora Mora, Higinio

    2003-01-01

    A new conception of flexible calculation that allows us to adjust a sum depending on the available time computation is presented. More specifically, the objective is to obtain a calculation model that makes the processing time/precision more flexible. The addition method is based on carry-select scheme adder and the proposed design uses precalculated data stored in look-up tables, which provide, above all, quality results and systematization in the implementation of low level primitives that ...

  4. Option values and flexibility preference

    OpenAIRE

    Strazzera, Elisabetta

    1998-01-01

    Preference for flexibility is a behavioral attitude displayed by people that prefer reversible to irreversible actions, and that are willing to pay a premium in order to maintain the possibility of changing their decision. This paper provides a functional characterization of preference for flexibility, based on the notion of option value. The proposed theory is shown to be useful to explain the success of marketing policies that guarantee reimbursement in consumption goods and financial marke...

  5. Investigating actinomycin D binding to G-quadruplex, i-motif and double-stranded DNA in 27-nt segment of c-MYC gene promoter.

    Science.gov (United States)

    Niknezhad, Zhila; Hassani, Leila; Norouzi, Davood

    2016-01-01

    c-MYC DNA is an attractive target for drug design, especially for cancer chemotherapy. Around 90% of c-MYC transcription is controlled by NHE III1, whose 27-nt purine-rich strand has the ability to form G-quadruplex structure. In this investigation, interaction of ActD with 27-nt G-rich strand (G/c-MYC) and its equimolar mixture with the complementary sequence, (GC/c-MYC) as well as related C-rich oligonucleotide (C/c-MYC) was evaluated. Molecular dynamic simulations showed that phenoxazine and lactone rings of ActD come close to the outer G-tetrad nucleotides indicating that ActD binds through end-stacking to the quadruplex DNA. RMSD and RMSF revealed that fluctuation of the quadruplex DNA increases upon interaction with the drug. The results of spectrophotometry and spectrofluorometry indicated that ActD most probably binds to the c-MYC quadruplex and duplex DNA via end-stacking and intercalation, respectively and polarity of ActD environment decreases due to the interaction. It was also found that binding of ActD to the GC-rich DNA is stronger than the two other forms of DNA. Circular dichroism results showed that the type of the three forms of DNA structures doesn't change, but their compactness alters due to their interaction with ActD. Finally, it can be concluded that ActD binds differently to double stranded DNA, quadruplex DNA and i-motif.

  6. Balancing energy flexibilities through aggregation

    DEFF Research Database (Denmark)

    Valsomatzis, Emmanouil; Hose, Katja; Pedersen, Torben Bach

    2014-01-01

    in both energy production and consumption, is the key to solving these problems. Flexibilities can be expressed as flex-offers, which due to their high number need to be aggregated to reduce the complexity of energy scheduling. In this paper, we discuss balance aggregation techniques that already......One of the main goals of recent developments in the Smart Grid area is to increase the use of renewable energy sources. These sources are characterized by energy fluctuations that might lead to energy imbalances and congestions in the electricity grid. Exploiting inherent flexibilities, which exist...... during aggregation aim at balancing flexibilities in production and consumption to reduce the probability of congestions and reduce the complexity of scheduling. We present results of our extensive experiments....

  7. Studies Of Residual Flexibility And Vibration Testing

    Science.gov (United States)

    Admire, John R.; Tinker, Michael L.; Bookout, Paul S.; Ivey, Edward W.

    1995-01-01

    Collection of reports presents theoretical and experimental studies in which concept of residual flexibility applied to modal vibration testing and verification of mathematical models of vibrations of flexible structure constrained by another structure. "Residual flexibility" denotes that part of interface flexibility due to mode shapes out of frequency range of test. Studies directed toward assessing residual-flexibility approach as substitute for fixed-base vibrational testing of payloads installed in spacecraft.

  8. Polymer electronics a flexible technology

    CERN Document Server

    Technology, Rapra

    2009-01-01

    The worldwide market for polymer electronic products has been estimated to be worth up to £15 billion by 2015 and the opportunity for new markets could be as high as £125 billion by 2025.'The rapid development of polymer electronics has revealed the possibility for transforming the electronics market by offering lighter, flexible and more cost effective alternatives to conventional materials and products. With applications ranging from printed, flexible conductors and novel semiconductor components to intelligent labels and large area displays and solar panels, products that were previously un

  9. Hydrophobic Core Flexibility Modulates Enzyme Activity in HIV-1 Protease

    Energy Technology Data Exchange (ETDEWEB)

    Mittal, Seema; Cai, Yufeng; Nalam, Madhavi N.L.; Bolon, Daniel N.A.; Schiffer, Celia A. (UMASS, MED)

    2012-09-11

    Human immunodeficiency virus Type-1 (HIV-1) protease is crucial for viral maturation and infectivity. Studies of protease dynamics suggest that the rearrangement of the hydrophobic core is essential for enzyme activity. Many mutations in the hydrophobic core are also associated with drug resistance and may modulate the core flexibility. To test the role of flexibility in protease activity, pairs of cysteines were introduced at the interfaces of flexible regions remote from the active site. Disulfide bond formation was confirmed by crystal structures and by alkylation of free cysteines and mass spectrometry. Oxidized and reduced crystal structures of these variants show the overall structure of the protease is retained. However, cross-linking the cysteines led to drastic loss in enzyme activity, which was regained upon reducing the disulfide cross-links. Molecular dynamics simulations showed that altered dynamics propagated throughout the enzyme from the engineered disulfide. Thus, altered flexibility within the hydrophobic core can modulate HIV-1 protease activity, supporting the hypothesis that drug resistant mutations distal from the active site can alter the balance between substrate turnover and inhibitor binding by modulating enzyme activity.

  10. Protein flexibility in the light of structural alphabets

    Directory of Open Access Journals (Sweden)

    Pierrick eCraveur

    2015-05-01

    Full Text Available Protein structures are valuable tools to understand protein function. Nonetheless, proteins are often considered as rigid macromolecules while their structures exhibit specific flexibility, which is essential to complete their functions. Analyses of protein structures and dynamics are often performed with a simplified three-state description, i.e. the classical secondary structures. . More precise and complete description of protein backbone conformation can be obtained using libraries of small protein fragments that are able to approximate every part of protein structures. These libraries, called structural alphabets (SAs, have been widely used in structure analysis field, from definition of ligand binding sites to superimposition of protein structures. SAs are also well suited to analyze the dynamics of protein structures.Here, we review innovative approaches that investigate protein flexibility based on SAs description. Coupled to various sources of experimental data (e.g. B-factor and computational methodology (e.g. Molecular Dynamic simulation, SAs turn out to be powerful tools to analyze protein dynamics, e.g. to examine allosteric mechanisms in large set of structures in complexes, to identify order/disorder transition. SAs were also shown to be quite efficient to predict protein flexibility from amino-acid sequence. Finally, in this review, we exemplify the interest of SAs for studying flexibility with different cases of proteins implicated in pathologies and diseases.

  11. Flexible Schedules and Shift Work.

    Science.gov (United States)

    Beers, Thomas M.

    2000-01-01

    Flexible work hours have gained prominence, as more than 25 million workers (27.6% of all full-time workers) can now vary their schedules. However, there has been little change since the mid-1980s in the proportion who work a shift other than a regular daytime shift. (JOW)

  12. States Seek Flexibility on Testing

    Science.gov (United States)

    McNeil, Michele; Gewertz, Catherine

    2013-01-01

    With the debut of common assessments less than two years away, states and districts are worried about the accountability systems that hinge on those tests. A growing chorus of policy groups is urging more flexibility in how states evaluate teachers, label schools, and enforce other high-stakes consequences during what's likely to be a messy…

  13. FLEXIBLE FLATFOOT IN CHILDREN (REVIEW

    Directory of Open Access Journals (Sweden)

    Владимир Маркович Кенис

    2014-06-01

    Full Text Available Flatfoot is one of the most common musculoskeletal conditions in the daily practice of pediatric orthopedists. Despite of numerous studies, diagnostic criteria and principles of management remain controversial. Flexible flatfoot - is visually detectable decrease in the height of the longitudinal arch of the foot, which can be spontaneously corrected by active or passive motion and not accompanied by any contracture of foot and ankle. Flexible flatfoot is a benign condition which is normal for childhood. But this term is also used to describe a painful deformity with marked limitation of dorsiflection and “not physiological” flatfoot with unfavorable course and prognosis. Despite of the awareness of the parents, flexible flatfoot does not lead to pain and should not be followed by any kind of treatment. Special shoe modifications and orthopedic insoles are useless in the attempt to improve the foot, but can influence negatively psychological condition and self-estimation. Proper diagnosis of flexible flatfoot is necessary in order to avoid unnecessary treatment and to reveal patients with adverse prognosis and rigid forms of flatfoot which need special approach.

  14. Creep behaviour of flexible adhesives

    NARCIS (Netherlands)

    Straalen, IJ.J. van; Botter, E.; Berg, A. van den; Beers, P. van

    2004-01-01

    Since flexible adhesives are used more and more in structural applications, designers should have a better understanding of its behaviour under various conditions as ultimate load, fatigue load, long-term load and environmental conditions. This paper focuses on long-term load conditions and its effe

  15. Easy and flexible mixture distributions

    DEFF Research Database (Denmark)

    Fosgerau, Mogens; Mabit, Stefan L.

    2013-01-01

    We propose a method to generate flexible mixture distributions that are useful for estimating models such as the mixed logit model using simulation. The method is easy to implement, yet it can approximate essentially any mixture distribution. We test it with good results in a simulation study...

  16. Flexibility in Language and Thought

    Science.gov (United States)

    Srinivasan, Mahesh

    2011-01-01

    Many words can be used flexibly: a book can be physically heavy, but also have provocative content, a "chicken" might live in a coop, but could also be tasty to eat. What do the uses of "polysemous" words such as these reveal about the structure of language and thought? Paper 1 examined 4-year-old children's representations of polysemous words…

  17. Flexible Query Answering Systems 2006

    DEFF Research Database (Denmark)

    -computer interaction. The overall theme of the FQAS conferences is innovative query systems aimed at providing easy, flexible, and intuitive access to information. Such systems are intended to facilitate retrieval from information repositories such as databases, libraries, and the World-Wide Web. These repositories...

  18. Functional flexibility and team performance

    NARCIS (Netherlands)

    Molleman, E.; Slomp, J.

    1999-01-01

    This study deals with workforce flexibility defined in terms of 'multifunctionality' and 'redundancy'. These concepts refer, respectively, to the number of different tasks a worker has mastered and the number of workers that are qualified to do a specific task. A third factor to be considered is wor

  19. Flexible Bistable Cholesteric Reflective Displays

    Science.gov (United States)

    Yang, Deng-Ke

    2006-03-01

    Cholesteric liquid crystals (ChLCs) exhibit two stable states at zero field condition-the reflecting planar state and the nonreflecting focal conic state. ChLCs are an excellent candidate for inexpensive and rugged electronic books and papers. This paper will review the display cell structure,materials and drive schemes for flexible bistable cholesteric (Ch) reflective displays.

  20. Flexible separator for alkaline batteries

    Science.gov (United States)

    Sheibley, D. W.

    1977-01-01

    Device is fabricated from low-cost readily-available commercial-materials by automated methods utilizing conventional paper coating processes. Flexibility of unit prevents cracking and disintegration caused by electrode warpage and dendrite growth, major causes of early battery failure with present separators.

  1. Polypharmacology within CXCR4: Multiple binding sites and allosteric behavior

    Science.gov (United States)

    Planesas, Jesús M.; Pérez-Nueno, Violeta I.; Borrell, José I.; Teixidó, Jordi

    2014-10-01

    CXCR4 is a promiscuous receptor, which binds multiple diverse ligands. As usual in promiscuous proteins, CXCR4 has a large binding site, with multiple subsites, and high flexibility. Hence, it is not surprising that it is involved in the phenomenon of allosteric modulation. However, incomplete knowledge of allosteric ligand-binding sites has hampered an in-depth molecular understanding of how these inhibitors work. For example, it is known that lipidated fragments of intracellular GPCR loops, so called pepducins, such as pepducin ATI-2341, modulate CXCR4 activity using an agonist allosteric mechanism. Nevertheless, there are also examples of small organic molecules, such as AMD11070 and GSK812397, which may act as antagonist allosteric modulators. Here, we give new insights into this issue by proposing the binding interactions between the CXCR4 receptor and the above-mentioned allosteric modulators. We propose that CXCR4 has minimum two topographically different allosteric binding sites. One allosteric site would be in the intracellular loop 1 (ICL1) where pepducin ATI-2341 would bind to CXCR4, and the second one, in the extracellular side of CXCR4 in a subsite into the main orthosteric binding pocket, delimited by extracellular loops n° 1, 2, and the N-terminal end, where antagonists AMD11070 and GSK812397 would bind. Prediction of allosteric interactions between CXCR4 and pepducin ATI-2341 were studied first by rotational blind docking to determine the main binding region and a subsequent refinement of the best pose was performed using flexible docking methods and molecular dynamics. For the antagonists AMD11070 and GSK812397, the entire CXCR4 protein surface was explored by blind docking to define the binding region. A second docking analysis by subsites of the identified binding region was performed to refine the allosteric interactions. Finally, we identified the binding residues that appear to be essential for CXCR4 (agonists and antagonists) allosteric

  2. Spectroscopic studies of the binding of Cu(II) complexes of oxicam NSAIDs to alternating G-C and homopolymeric G-C sequences

    Science.gov (United States)

    Chakraborty, Sreeja; Bose, Madhuparna; Sarkar, Munna

    2014-03-01

    Drugs belonging to the Non-steroidal anti-inflammatory (NSAID) group are not only used as anti-inflammatory, analgesic and anti-pyretic agents, but also show anti-cancer effects. Complexing them with a bioactive metal like copper, show an enhancement in their anti-cancer effects compared to the bare drugs, whose exact mechanism of action is not yet fully understood. For the first time, it was shown by our group that Cu(II)-NSAIDs can directly bind to the DNA backbone. The ability of the copper complexes of NSAIDs namely meloxicam and piroxicam to bind to the DNA backbone could be a possible molecular mechanism behind their enhanced anticancer effects. Elucidating base sequence specific interaction of Cu(II)-NSAIDs to the DNA will provide information on their possible binding sites in the genome sequence. In this work, we present how these complexes respond to differences in structure and hydration pattern of GC rich sequences. For this, binding studies of Cu(II) complexes of piroxicam [Cu(II)-(Px)2 (L)2] and meloxicam [Cu(II)-(Mx)2 (L)] with alternating GC (polydG-dC) and homopolymeric GC (polydG-polydC) sequences were carried out using a combination of spectroscopic techniques that include UV-Vis absorption, fluorescence and circular dichroism (CD) spectroscopy. The Cu(II)-NSAIDs show strong binding affinity to both polydG-dC and polydG-polydC. The role reversal of Cu(II)-meloxicam from a strong binder of polydG-dC (Kb = 11.5 × 103 M-1) to a weak binder of polydG-polydC (Kb = 5.02 × 103 M-1), while Cu(II)-piroxicam changes from a strong binder of polydG-polydC (Kb = 8.18 × 103 M-1) to a weak one of polydG-dC (Kb = 2.18 × 103 M-1), point to the sensitivity of these complexes to changes in the backbone structures/hydration. Changes in the profiles of UV absorption band and CD difference spectra, upon complex binding to polynucleotides and the results of competitive binding assay using ethidium bromide (EtBr) fluorescence indicate different binding modes in each

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

    Directory of Open Access Journals (Sweden)

    V Joachim Haupt

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

  4. Docking validation resources: protein family and ligand flexibility experiments.

    Science.gov (United States)

    Mukherjee, Sudipto; Balius, Trent E; Rizzo, Robert C

    2010-11-22

    A database consisting of 780 ligand-receptor complexes, termed SB2010, has been derived from the Protein Databank to evaluate the accuracy of docking protocols for regenerating bound ligand conformations. The goal is to provide easily accessible community resources for development of improved procedures to aid virtual screening for ligands with a wide range of flexibilities. Three core experiments using the program DOCK, which employ rigid (RGD), fixed anchor (FAD), and flexible (FLX) protocols, were used to gauge performance by several different metrics: (1) global results, (2) ligand flexibility, (3) protein family, and (4) cross-docking. Global spectrum plots of successes and failures vs rmsd reveal well-defined inflection regions, which suggest the commonly used 2 Å criteria is a reasonable choice for defining success. Across all 780 systems, success tracks with the relative difficulty of the calculations: RGD (82.3%) > FAD (78.1%) > FLX (63.8%). In general, failures due to scoring strongly outweigh those due to sampling. Subsets of SB2010 grouped by ligand flexibility (7-or-less, 8-to-15, and 15-plus rotatable bonds) reveal that success degrades linearly for FAD and FLX protocols, in contrast to RGD, which remains constant. Despite the challenges associated with FLX anchor orientation and on-the-fly flexible growth, success rates for the 7-or-less (74.5%) and, in particular, the 8-to-15 (55.2%) subset are encouraging. Poorer results for the very flexible 15-plus set (39.3%) indicate substantial room for improvement. Family-based success appears largely independent of ligand flexibility, suggesting a strong dependence on the binding site environment. For example, zinc-containing proteins are generally problematic, despite moderately flexible ligands. Finally, representative cross-docking examples, for carbonic anhydrase, thermolysin, and neuraminidase families, show the utility of family-based analysis for rapid identification of particularly good or bad

  5. Total iron binding capacity

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003489.htm Total iron binding capacity To use the sharing features on this page, please enable JavaScript. Total iron binding capacity (TIBC) is a blood test to ...

  6. Plant Hormone Binding Sites

    OpenAIRE

    Napier, Richard

    2004-01-01

    • Aims Receptors for plant hormones are becoming identified with increasing rapidity, although a frustrating number remain unknown. There have also been many more hormone‐binding proteins described than receptors. This Botanical Briefing summarizes what has been discovered about hormone binding sites, their discovery and descriptions, and will not dwell on receptor functions or activities except where these are relevant to understand binding.

  7. Analysis of binding heterogeneity.

    NARCIS (Netherlands)

    Nederlof, M.M.

    1992-01-01

    Binding heterogeneity, due to different functional groups on a reactive surface, plays an important role in the binding of small molecules or ions to many adsorbents, both in industrial processes and in natural environments. The binding heterogeneity is described by a distribution of affinity consta

  8. Lost and Found in Flexibility

    DEFF Research Database (Denmark)

    Bødker, Susanne; Christiansen, Ellen

    2002-01-01

    'New work' is characterized by mobility and flexibility and a growing need to facilitate social awareness. The paper discusses how to augment the environment with social awareness and suggest 'awareness-in-transition' as a lable for awareness in mobile work in flexible work environments, and as...... locus for building social awareness in the 'new work'. A transition (e.g. taking information from a whiteboard in a meeting room to the desktop of a personal computer)--besides the immediate implications at the functional level--has important interpersonal, intra-personal, and organizational...... implications for the building of a social awareness among the collaborators, because it builds on recognition of difference in the environment. Building on Grudin's 'Eight Challenges for the Developers' of Computer Supported Cooperative Work, through analysis of a scenario and two experiments based on case...

  9. Flexible Temperature Sensors on Fibers

    Directory of Open Access Journals (Sweden)

    Marcin Sloma

    2010-08-01

    Full Text Available The aim of this paper is to present research dedicated to the elaboration of novel, miniaturized flexible temperature sensors for textronic applications. Examined sensors were manufactured on a single yarn, which ensures their high flexibility and good compatibility with textiles. Stable and linear characteristics were obtained by special technological process and applied temperature profiles. As a thermo-sensitive materials the innovative polymer compositions filled with multiwalled carbon nanotubes were used. Elaborated material was adapted to printing and dip-coating techniques to produce NTC composites. Nanotube sensors were free from tensometric effect typical for other carbon-polymer sensor, and demonstrated TCR of 0.13%/K. Obtained temperature sensors, compatible with textile structure, can be applied in rapidly developing smart textiles and be used for health and protections purposes.

  10. Flexible Adaptation in Cognitive Radios

    CERN Document Server

    Li, Shujun

    2013-01-01

    This book provides an introduction to software-defined radio and cognitive radio, along with methodologies for applying knowledge representation, semantic web, logic reasoning and artificial intelligence to cognitive radio, enabling autonomous adaptation and flexible signaling. Readers from the wireless communications and software-defined radio communities will use this book as a reference to extend software-defined radio to cognitive radio, using the semantic technology described. Readers with a background in semantic web and artificial intelligence will find in this book the application of semantic web and artificial intelligence technologies to wireless communications. For readers in networks and network management, this book presents a new approach to enable interoperability, collaborative optimization and flexible adaptation of network components. Provides a comprehensive ontology covering the core concepts of wireless communications using a formal language; Presents the technical realization of using a ...

  11. ULTRA BARRIER TOPSHEET (UBT) FOR FLEXIBLE PHOTOVOLTAICS

    Energy Technology Data Exchange (ETDEWEB)

    DeScioli, Derek

    2013-06-01

    This slide-show presents 3M photovoltaic-related products, particularly flexible components. Emphasis is on the 3M Ultra Barrier Solar Films. Topics covered include reliability and qualification testing and flexible photovoltaic encapsulation costs.

  12. WAGE FLEXIBILITY IN THE CONTEMPORARY SOCIETY

    Directory of Open Access Journals (Sweden)

    TECULESCU Silviu Alexandru

    2010-12-01

    Full Text Available The paper follows to offer the most efficient solutions for the attainment by Romania of the economic development level associated to the Western European countries. It proposes the division of the flexibility of labour market in three components, namely: internal flexibility, external flexibility and wage flexibility. The analysis performed within the present study will emphasize the wage flexibility. Wage flexibility can be classified in four components: a plans of individual and group incentives; b plans of assigning wages out of productivity; c plans of distribution of profits and, respectively, d plans of suggestions. The labour market flexibility, in general, and especially the wage flexibility contributes to the increase of employee motivation at the workplace, aspect which leeds to the growth of labour productivity, through this one being put the bases of the medium- and long-term economic development.

  13. Understanding flexible and distributed software development processes

    OpenAIRE

    Agerfalk, Par J.; Fitzgerald, Brian

    2006-01-01

    peer-reviewed The minitrack on Flexible and Distributed Software Development Processes addresses two important and partially intertwined current themes in software development: process flexibility and globally distributed software development

  14. Thermodynamics of tubelike flexible polymers

    OpenAIRE

    Vogel, T.; Neuhaus, T; Bachmann, M.; Janke, W.

    2009-01-01

    In this work, we discuss the general phase behavior of short tubelike flexible polymers. The geometric thickness constraint is implemented through the concept of the global radius of curvature. We use sophisticated Monte Carlo sampling methods to simulate small bead-stick polymer models with Lennard-Jones interaction among nonbonded monomers. We analyze energetic fluctuations and structural quantities to classify conformational pseudophases. We find that the tube thickness influences the ther...

  15. Flexible mental calculation and "Zahlenblickschulung"

    OpenAIRE

    Rechtsteiner-Merz, Charlotte; Rathgeb-Schnierer, Elisabeth

    2015-01-01

    International audience; The study focuses on the development of mental calculation of elementary students who show difficulties in learning math. In total, 20 children in 8 classes were observed during their first year at school. The math education of five classes was based on a special approach called “Zahlenblickschulung”, whereas three classes experienced more regular lessons. The collected data allowed a development of a typology of flexibility in mental calculation. Additionally, it was ...

  16. Has compensation become more flexible?

    OpenAIRE

    Sandra A. Cannon; Bruce C. Fallick; Michael Lettau; Raven E. Saks

    2000-01-01

    In recent years, numerous observers have argued that global competition, increased reliance on contingent workers, and the breakdown of implicit contracts have made compensation practices in the United States more flexible; in particular, employers have become more concerned with how an employee's pay compares to that in other firms and less concerned with considerations of equity or relative pay within the firm. This paper uses establishment-level data from the Bureau of Labor Statistics' Em...

  17. Flexible Borescope For Inspecting Ducts

    Science.gov (United States)

    Shinozaki, Keith; Armstrong, Mike P.; Urquidi, Ron

    1995-01-01

    Borescope and associated equipment developed specifically for use in optical inspection of inside of flexible joints in rocket-engine fuel duct. Apparatus includes assembly, characterized as "mouse/canoe," at sensing end of 10-ft borescope cable. Borescope tip rides in mouse/canoe. The mouse/canoe made laterally compressible, to facilitate movement past constrictions and provides fixed distance from inspection point permitting accurate description in duct inspected.

  18. CRISIS FOCUS Uncertainty and Flexibility

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    As the world continued to watch the unfolding financial and economic crises this month, Robert Zoellick, President of the World Bank, arrived in China for discussions on how the country can help support the global economy and the efforts it has taken to strengthen its own recovery. Zoellick, who had seen many uncertainties in 2009, called for China to be flexible with its macroeconomic policy. He made the following comments at a press conference in Beijing on December 15. Edited excerpts follow:

  19. The Flexibility of Ectopic Lipids

    Science.gov (United States)

    Loher, Hannah; Kreis, Roland; Boesch, Chris; Christ, Emanuel

    2016-01-01

    In addition to the subcutaneous and the visceral fat tissue, lipids can also be stored in non-adipose tissue such as in hepatocytes (intrahepatocellular lipids; IHCL), skeletal (intramyocellular lipids; IMCL) or cardiac muscle cells (intracardiomyocellular lipids; ICCL). Ectopic lipids are flexible fuel stores that can be depleted by physical exercise and repleted by diet. They are related to obesity and insulin resistance. Quantification of IMCL was initially performed invasively, using muscle biopsies with biochemical and/or histological analysis. 1H-magnetic resonance spectroscopy (1H-MRS) is now a validated method that allows for not only quantifying IMCL non-invasively and repeatedly, but also assessing IHCL and ICCL. This review summarizes the current available knowledge on the flexibility of ectopic lipids. The available evidence suggests a complex interplay between quantitative and qualitative diet, fat availability (fat mass), insulin action, and physical exercise, all important factors that influence the flexibility of ectopic lipids. Furthermore, the time frame of the intervention on these parameters (short-term vs. long-term) appears to be critical. Consequently, standardization of physical activity and diet are critical when assessing ectopic lipids in predefined clinical situations. PMID:27649157

  20. The Flexibility of Ectopic Lipids

    Directory of Open Access Journals (Sweden)

    Hannah Loher

    2016-09-01

    Full Text Available In addition to the subcutaneous and the visceral fat tissue, lipids can also be stored in non-adipose tissue such as in hepatocytes (intrahepatocellular lipids; IHCL, skeletal (intramyocellular lipids; IMCL or cardiac muscle cells (intracardiomyocellular lipids; ICCL. Ectopic lipids are flexible fuel stores that can be depleted by physical exercise and repleted by diet. They are related to obesity and insulin resistance. Quantification of IMCL was initially performed invasively, using muscle biopsies with biochemical and/or histological analysis. 1H-magnetic resonance spectroscopy (1H-MRS is now a validated method that allows for not only quantifying IMCL non-invasively and repeatedly, but also assessing IHCL and ICCL. This review summarizes the current available knowledge on the flexibility of ectopic lipids. The available evidence suggests a complex interplay between quantitative and qualitative diet, fat availability (fat mass, insulin action, and physical exercise, all important factors that influence the flexibility of ectopic lipids. Furthermore, the time frame of the intervention on these parameters (short-term vs. long-term appears to be critical. Consequently, standardization of physical activity and diet are critical when assessing ectopic lipids in predefined clinical situations.

  1. The Flexibility of Ectopic Lipids.

    Science.gov (United States)

    Loher, Hannah; Kreis, Roland; Boesch, Chris; Christ, Emanuel

    2016-01-01

    In addition to the subcutaneous and the visceral fat tissue, lipids can also be stored in non-adipose tissue such as in hepatocytes (intrahepatocellular lipids; IHCL), skeletal (intramyocellular lipids; IMCL) or cardiac muscle cells (intracardiomyocellular lipids; ICCL). Ectopic lipids are flexible fuel stores that can be depleted by physical exercise and repleted by diet. They are related to obesity and insulin resistance. Quantification of IMCL was initially performed invasively, using muscle biopsies with biochemical and/or histological analysis. ¹H-magnetic resonance spectroscopy (¹H-MRS) is now a validated method that allows for not only quantifying IMCL non-invasively and repeatedly, but also assessing IHCL and ICCL. This review summarizes the current available knowledge on the flexibility of ectopic lipids. The available evidence suggests a complex interplay between quantitative and qualitative diet, fat availability (fat mass), insulin action, and physical exercise, all important factors that influence the flexibility of ectopic lipids. Furthermore, the time frame of the intervention on these parameters (short-term vs. long-term) appears to be critical. Consequently, standardization of physical activity and diet are critical when assessing ectopic lipids in predefined clinical situations. PMID:27649157

  2. Flexible Thermoelectric Device for Localized Thermal Management

    OpenAIRE

    Lee, Minjae

    2016-01-01

    Flexible thermoelectric (TE) refrigerators are attractive for personalized thermal management, for example, when integrated into clothes. Flexible TE power generators can also find applications in wearable self-powered mobile electronics. These devices, however, need high thermoelectric performance and mechanical flexibility under compressive and tensile strains, a combination of device properties that are often difficult to achieve. Despite significant efforts in the field, flexible TE devic...

  3. Analyzing radioligand binding data.

    Science.gov (United States)

    Motulsky, Harvey; Neubig, Richard

    2002-08-01

    Radioligand binding experiments are easy to perform, and provide useful data in many fields. They can be used to study receptor regulation, discover new drugs by screening for compounds that compete with high affinity for radioligand binding to a particular receptor, investigate receptor localization in different organs or regions using autoradiography, categorize receptor subtypes, and probe mechanisms of receptor signaling, via measurements of agonist binding and its regulation by ions, nucleotides, and other allosteric modulators. This unit reviews the theory of receptor binding and explains how to analyze experimental data. Since binding data are usually best analyzed using nonlinear regression, this unit also explains the principles of curve fitting with nonlinear regression.

  4. 21 CFR 868.5530 - Flexible laryngoscope.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Flexible laryngoscope. 868.5530 Section 868.5530...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5530 Flexible laryngoscope. (a) Identification. A flexible laryngoscope is a fiberoptic device used to examine and visualize a patient's...

  5. Flexible Work Options within the Organisational System

    Science.gov (United States)

    Albion, Majella J.; Chee, Munli

    2006-01-01

    The availability of flexible work options provides an opportunity for individuals to shape their careers in order to optimise their work and life goals. This study takes a systems theory approach to examine how the use of flexible work options influences relationships and interactions in the workplace. The "Flexible Work Options Questionnaire"…

  6. Financial Flexibility in North Carolina Schools.

    Science.gov (United States)

    Suarez, Tanya M.; Polen, Deborah A.

    This paper explores educational financial flexibility with a focus on the specific issues surrounding local flexibility in North Carolina school districts. Strategies that states have used to increase local financial flexibility include waivers, reduction of budget categories, block grants, and school-based budgeting. The North Carolina system of…

  7. Towards Measuring Investment in Flexible Foundry Manufacturing

    Directory of Open Access Journals (Sweden)

    Rhythm Suren Wadhwa

    2012-07-01

    Full Text Available Manufacturing flexibility is an important instrument to ensure the success of manufacturing systems in the modern day competitive and uncertain environment. The major hindrance in integrating flexibility into decision making process is that it is difficult to measure and be compared to future indefinable manufacturing scenarios. This paper presents a methodical concept utilizing real options to evaluate flexible foundry manufacturing system.

  8. Measurement of Residual Flexibility for Substructures Having Prominent Flexible Interfaces

    Science.gov (United States)

    Tinker, Michael L.; Bookout, Paul S.

    1994-01-01

    Verification of a dynamic model of a constrained structure requires a modal survey test of the physical structure and subsequent modification of the model to obtain the best agreement possible with test data. Constrained-boundary or fixed-base testing has historically been the most common approach for verifying constrained mathematical models, since the boundary conditions of the test article are designed to match the actual constraints in service. However, there are difficulties involved with fixed-base testing, in some cases making the approach impractical. It is not possible to conduct a truly fixed-base test due to coupling between the test article and the fixture. In addition, it is often difficult to accurately simulate the actual boundary constraints, and the cost of designing and constructing the fixture may be prohibitive. For use when fixed-base testing proves impractical or undesirable, alternate free-boundary test methods have been investigated, including the residual flexibility technique. The residual flexibility approach has been treated analytically in considerable detail and has had limited frequency response measurements for the method. This concern is well-justified for a number of reasons. First, residual flexibilities are very small numbers, typically on the order of 1.0E-6 in/lb for translational diagonal terms, and orders of magnitude smaller for off-diagonal values. This poses difficulty in obtaining accurate and noise-free measurements, especially for points removed from the excitation source. A second difficulty encountered in residual measurements lies in obtaining a clean residual function in the process of subtracting synthesized modal data from a measured response function. Inaccuracies occur since modes are not subtracted exactly, but only to the accuracy of the curve fits for each mode; these errors are compounded with increasing distance from the excitation point. In this paper, the residual flexibility method is applied to a simple

  9. Structure-based druggability assessment of the mammalian structural proteome with inclusion of light protein flexibility.

    Directory of Open Access Journals (Sweden)

    Kathryn A Loving

    2014-07-01

    Full Text Available Advances reported over the last few years and the increasing availability of protein crystal structure data have greatly improved structure-based druggability approaches. However, in practice, nearly all druggability estimation methods are applied to protein crystal structures as rigid proteins, with protein flexibility often not directly addressed. The inclusion of protein flexibility is important in correctly identifying the druggability of pockets that would be missed by methods based solely on the rigid crystal structure. These include cryptic pockets and flexible pockets often found at protein-protein interaction interfaces. Here, we apply an approach that uses protein modeling in concert with druggability estimation to account for light protein backbone movement and protein side-chain flexibility in protein binding sites. We assess the advantages and limitations of this approach on widely-used protein druggability sets. Applying the approach to all mammalian protein crystal structures in the PDB results in identification of 69 proteins with potential druggable cryptic pockets.

  10. Increase in flexibility with latest technologies

    Energy Technology Data Exchange (ETDEWEB)

    Fuebi, Michael; Krull, Florian Felix [RWE Technology GmbH, Essen (Germany); Ladwig, Michael [Alstom (Switzerland) AG, Baden (Switzerland)

    2012-07-01

    Flexibility demands on conventional power plants rise to ensure grid stability within a power generation mix with drastically increasing capacities of renewable power generation sources such as wind farms and photovoltaics. In this paper flexibility requirements for a power plant portfolio are discussed. Through selected examples of projects from RWE's current investment programme, comprising around 13 GW of efficient and flexible power plant capacity in Germany, the Netherlands, Turkey and the UK, application of the latest technologies to fulfil flexibility requirements is presented. Further, the potential of smart retrofits in terms of combined flexibility and efficiency gains is illustrated by means of an existing power plant unit retrofit project. (orig.)

  11. Analysis of binding behavior between dynamic structures of a papain and the peptide consisting of 10 GLY residues

    Science.gov (United States)

    Nishiyama, Katsuhiko

    2010-07-01

    The binding of 10GLY to dynamic structures of papain was investigated by molecular dynamics and docking simulations. The binding free energies and sites were greatly fluctuated depending on the time and the binding was more stable and existed at the near site of active center when the structural changes in the highly flexible residues in papain were larger. Binding stability and sites would be significantly influenced by the highly flexible residues. Analysis of such residues would provide an important guideline for clarification of enzymatic activities and modification of structural dynamics of such residues would allow us to control enzymatic activities.

  12. Cognitive Flexibility in Primary Dystonia.

    Science.gov (United States)

    Lange, Florian; Seer, Caroline; Dengler, Reinhard; Dressler, Dirk; Kopp, Bruno

    2016-07-01

    Objectives Although primary dystonia is typically characterized as a movement disorder, it is also associated with cognitive alterations in the domain of executive functioning which may arise from changes in cortico-basal ganglia circuits. Specifically, in comparison to healthy controls, patients with dystonia show deficits in neuropsychological tests of cognitive flexibility. However, it is unclear whether cognitive inflexibility is caused by the pathomechanisms underlying primary dystonia or by confounding factors such as depression or symptom-related distraction.Methods The present study aimed to eliminate these confounds by examining cognitive flexibility in dystonia patients and in patients with similar motor symptoms but without a comparable central pathophysiology. Eighteen patients with primary blepharospasm, a common form of dystonia affecting the muscles around the eyes, and 19 patients with hemifacial spasm, a facial nerve disorder causing similar eyelid spasms, completed a computerized version of the Wisconsin Card Sorting Test (cWCST). The two groups were further compared on tests of global cognitive functioning, psychiatric symptoms, health status, and impulsiveness. Results Blepharospasm patients committed significantly more errors on the cWCST than patients with hemifacial spasm. Group differences were most pronounced with regard to integration errors, a measure of rule-inference processes on the cWCST. Integration errors were also associated with impulsiveness in patients with blepharospasm. Conclusions Primary blepharospasm is related to deficits in cognitive flexibility, even when blepharospasm patients are compared with patients who suffer from motor symptoms of non-dystonic origin. Our results support the possibility that cognitive inflexibility results from the specific pathophysiological processes underlying primary dystonia. (JINS, 2016, 22, 662-670). PMID:27333537

  13. Consumer flexibility - State and challenges

    International Nuclear Information System (INIS)

    This report summarises experiences and results from relevant projects carried out within the area of consumer flexibility in the last years. A general description of the projects is presented. In addition are testing activities, economical signals for motivating the end user for load reductions and appropriate technology for communication and effect management mentioned separately. Briefly summarised is the following achieved: 1) The potential for effect regulating measures in ordinary consumption and in power demanding industry is analysed and estimated to 1750 MW and 3360 MW respectively. 2) Time varied rates are developed and are tested. The NVE has decided on this basis that all the network owners should offer season varied rates to their customers. 3) Test projects in Drammen, Oslo and Trondheim have shown that it is possible to motivate smaller consumers for and implement load reductions. 4) Technology for load management for the end user is evaluated. 5) A survey is made viewing the technology for two way communication. In addition the ''option'' market for the reserves of the Statnett has proved that a steady compensation is a sufficient incentive for producing substantial effect reserves in the load sector (power intensive industry). In the last part of the report the incentives and frame conditions for establishing technical solutions and infrastructure are discussed. Further work will focus on the consumer flexibility in shortage situations. The main challenges are connected to: 1) Establishing a foundation for decisions concerning cost efficient investments in necessary technical equipment. 2) To find an optimal combination of a price flexible and remote controlled load reduction

  14. Flexible varieties and automorphism groups

    CERN Document Server

    Arzhantsev, I; Kaliman, S; Kutzschebauch, F; Zaidenberg, M

    2010-01-01

    Given an affine algebraic variety X of dimension at least 2, we let SAut (X) denote the special automorphism group of X i.e., the subgroup of the full automorphism group Aut (X) generated by all one-parameter unipotent subgroups. We show that if SAut (X) is transitive on the smooth locus of X then it is infinitely transitive on this locus. In turn, the transitivity is equivalent to the flexibility of X. The latter means that for every smooth point x of X the tangent space at x is spanned by the velocity vectors of one-parameter unipotent subgroups of Aut (X). We provide also different variations and applications.

  15. Flexible varieties and automorphism groups

    OpenAIRE

    Arzhantsev, I.; Flenner, H.; Kaliman, S.; Kutzschebauch, F.; Zaidenberg, M

    2013-01-01

    Given an irreducible affine algebraic variety $X$ of dimension $n\\ge2$ , we let $\\operatorname {SAut}(X)$ denote the special automorphism group of $X$ , that is, the subgroup of the full automorphism group $\\operatorname{Aut}(X)$ generated by all one-parameter unipotent subgroups. We show that if $\\operatorname {SAut}(X)$ is transitive on the smooth locus $X_{\\mathrm{reg}}$ , then it is infinitely transitive on $X_{\\mathrm{reg}}$ . In turn, the transitivity is equivalent to the flexibility of...

  16. Flexible spintronic devices on Kapton

    DEFF Research Database (Denmark)

    Bedoya-Pinto, Amilcar; Donolato, Marco; Gobbi, Marco;

    2014-01-01

    Magnetic tunnel junctions and nano-sized domain-wall conduits have been fabricated on the flexible substrate Kapton. Despite the delicate nature of tunneling barriers and zig-zag shaped nanowires, the devices show an outstanding integrity and robustness upon mechanical bending. High values...... of bending angle (r = 5 mm) have been achieved without degradation of the device performance, reaching room-temperature tunneling magnetoresistance ratios of 12% in bended Co/Al2O3/NiFe junctions. In addition, a suitable route to pattern high-quality nanostructures directly on the polyimide surface...

  17. Protein flexibility oriented virtual screening strategy for JAK2 inhibitors

    Science.gov (United States)

    Xiong, Xiao; Yuan, Haoliang; Zhang, Yanmin; Xu, Jinxing; Ran, Ting; Liu, Haichun; Lu, Shuai; Xu, Anyang; Li, Hongmei; Jiang, Yulei; Lu, Tao; Chen, Yadong

    2015-10-01

    JAK2 has been considered as an important target for the development of anti-cancer agents. In this study, considering the flexibility of its binding site, an integrated strategy combining Bayesian categorization modeling and ensemble docking was established. Four representative crystal structures were selected for ensemble docking by the hierarchical clustering of 34 crystal structures according to the volume overlaps of each structure. A retrospective virtual screening was performed to validate this integrated strategy. As the preliminary filtration, the Bayesian model enhanced the ratio of actives by reducing the large amount of decoys. After docking the remaining compounds, the comparison between the ensemble and individual results showed that the enrichment of ensemble docking improved significantly. The results of analysis on conformational changes of two top ranked active inhibitors when docking into different proteins indicated that compounds with flexible conformations well fitted the different binding site shapes were more likely to be potential JAK2 inhibitors. This high efficient strategy will facilitate virtual screening for novel JAK2 inhibitors and could be even applied in drug discovery against other targets.

  18. Python bindings for libcloudph++

    OpenAIRE

    Jarecka, Dorota; Arabas, Sylwester; Del Vento, Davide

    2015-01-01

    This technical note introduces the Python bindings for libcloudph++. The libcloudph++ is a C++ library of algorithms for representing atmospheric cloud microphysics in numerical models. The bindings expose the complete functionality of the library to the Python users. The bindings are implemented using the Boost.Python C++ library and use NumPy arrays. This note includes listings with Python scripts exemplifying the use of selected library components. An example solution for using the Python ...

  19. DNS & Bind Cookbook

    CERN Document Server

    Liu, Cricket

    2011-01-01

    The DNS & BIND Cookbook presents solutions to the many problems faced by network administrators responsible for a name server. Following O'Reilly's popular problem-and-solution cookbook format, this title is an indispensable companion to DNS & BIND, 4th Edition, the definitive guide to the critical task of name server administration. The cookbook contains dozens of code recipes showing solutions to everyday problems, ranging from simple questions, like, "How do I get BIND?" to more advanced topics like providing name service for IPv6 addresses. It's full of BIND configuration files that yo

  20. Python bindings for libcloudph++

    CERN Document Server

    Jarecka, Dorota; Del Vento, Davide

    2015-01-01

    This technical note introduces the Python bindings for libcloudph++. The libcloudph++ is a C++ library of algorithms for representing atmospheric cloud microphysics in numerical models. The bindings expose the complete functionality of the library to the Python users. The bindings are implemented using the Boost.Python C++ library and use NumPy arrays. This note includes listings with Python scripts exemplifying the use of selected library components. An example solution for using the Python bindings to access libcloudph++ from Fortran is presented.

  1. Extracellular-regulated kinase 2 is activated by the enhancement of hinge flexibility.

    Science.gov (United States)

    Sours, Kevin M; Xiao, Yao; Ahn, Natalie G

    2014-05-01

    Protein motions underlie conformational and entropic contributions to enzyme catalysis; however, relatively little is known about the ways in which this occurs. Studies of the mitogen-activated protein kinase ERK2 (extracellular-regulated protein kinase 2) by hydrogen-exchange mass spectrometry suggest that activation enhances backbone flexibility at the linker between N- and C-terminal domains while altering nucleotide binding mode. Here, we address the hypothesis that enhanced backbone flexibility within the hinge region facilitates kinase activation. We show that hinge mutations enhancing flexibility promote changes in the nucleotide binding mode consistent with domain movement, without requiring phosphorylation. They also lead to the activation of monophosphorylated ERK2, a form that is normally inactive. The hinge mutations bypass the need for pTyr but not pThr, suggesting that Tyr phosphorylation controls hinge motions. In agreement, monophosphorylation of pTyr enhances both hinge flexibility and nucleotide binding mode, measured by hydrogen-exchange mass spectrometry. Our findings demonstrate that regulated protein motions underlie kinase activation. Our working model is that constraints to domain movement in ERK2 are overcome by phosphorylation at pTyr, which increases hinge dynamics to promote the active conformation of the catalytic site.

  2. Flexible network wireless transceiver and flexible network telemetry transceiver

    Science.gov (United States)

    Brown, Kenneth D.

    2008-08-05

    A transceiver for facilitating two-way wireless communication between a baseband application and other nodes in a wireless network, wherein the transceiver provides baseband communication networking and necessary configuration and control functions along with transmitter, receiver, and antenna functions to enable the wireless communication. More specifically, the transceiver provides a long-range wireless duplex communication node or channel between the baseband application, which is associated with a mobile or fixed space, air, water, or ground vehicle or other platform, and other nodes in the wireless network or grid. The transceiver broadly comprises a communication processor; a flexible telemetry transceiver including a receiver and a transmitter; a power conversion and regulation mechanism; a diplexer; and a phased array antenna system, wherein these various components and certain subcomponents thereof may be separately enclosed and distributable relative to the other components and subcomponents.

  3. Structures of apo IRF-3 and IRF-7 DNA binding domains: effect of loop L1 on DNA binding

    Energy Technology Data Exchange (ETDEWEB)

    De Ioannes, Pablo; Escalante, Carlos R.; Aggarwal, Aneel K. (VCU); (Mount Sinai Hospital)

    2013-11-20

    Interferon regulatory factors IRF-3 and IRF-7 are transcription factors essential in the activation of interferon-{beta} (IFN-{beta}) gene in response to viral infections. Although, both proteins recognize the same consensus IRF binding site AANNGAAA, they have distinct DNA binding preferences for sites in vivo. The X-ray structures of IRF-3 and IRF-7 DNA binding domains (DBDs) bound to IFN-{beta} promoter elements revealed flexibility in the loops (L1-L3) and the residues that make contacts with the target sequence. To characterize the conformational changes that occur on DNA binding and how they differ between IRF family members, we have solved the X-ray structures of IRF-3 and IRF-7 DBDs in the absence of DNA. We found that loop L1, carrying the conserved histidine that interacts with the DNA minor groove, is disordered in apo IRF-3 but is ordered in apo IRF-7. This is reflected in differences in DNA binding affinities when the conserved histidine in loop L1 is mutated to alanine in the two proteins. The stability of loop L1 in IRF-7 derives from a unique combination of hydrophobic residues that pack against the protein core. Together, our data show that differences in flexibility of loop L1 are an important determinant of differential IRF-DNA binding.

  4. Relationship between conformational flexibility and chelate cooperativity.

    Science.gov (United States)

    Misuraca, M Cristina; Grecu, Tudor; Freixa, Zoraida; Garavini, Valentina; Hunter, Christopher A; van Leeuwen, Piet W N M; Segarra-Maset, M Dolores; Turega, Simon M

    2011-04-15

    A family of four biscarbamates (AA) and four bisphenols (DD) were synthesized, and H-bonding interactions between all AA•DD combinations were characterized using (1)H NMR titrations in carbon tetrachloride. A chemical double mutant cycle analysis shows that there are no secondary electrostatic interactions or allosteric cooperativity in these systems, and the system therefore provides an ideal platform for investigating the relationship between chemical structure and chelate cooperativity. Effective molarities (EMs) were measured for 12 different systems, where the number of rotors in the chains connecting the two H-bond sites was varied from 5 to 20. The association constants vary by less than an order of magnitude for all 12 complexes, and the variation in EM is remarkably small (0.1-0.9 M). The results provide a relationship between EM and the number of rotors in the connecting chains (r): EM ≈ 10r(-3/2). The value of 10 M is the upper limit for the value of EM for a noncovalent intramolecular interaction. Introduction of rotors reduces the value of EM from this maximum in accord with a random walk analysis of the encounter probability of the chain ends (r(-3/2)). Noncovalent EMs never reach the very high values observed for covalent processes, which places limitations on the magnitudes of the effects that one is likely to achieve through the use of chelate cooperativity in supramolecular assembly and catalysis. On the other hand, the decrease in EM due to the introduction of conformational flexibility is less dramatic than one might expect based on the behavior of covalent systems, which limits the losses in binding affinity caused by poor preorganization of the interaction sites.

  5. Ligand photo-isomerization triggers conformational changes in iGluR2 ligand binding domain.

    Directory of Open Access Journals (Sweden)

    Tino Wolter

    Full Text Available Neurological glutamate receptors bind a variety of artificial ligands, both agonistic and antagonistic, in addition to glutamate. Studying their small molecule binding properties increases our understanding of the central nervous system and a variety of associated pathologies. The large, oligomeric multidomain membrane protein contains a large and flexible ligand binding domains which undergoes large conformational changes upon binding different ligands. A recent application of glutamate receptors is their activation or inhibition via photo-switchable ligands, making them key systems in the emerging field of optochemical genetics. In this work, we present a theoretical study on the binding mode and complex stability of a novel photo-switchable ligand, ATA-3, which reversibly binds to glutamate receptors ligand binding domains (LBDs. We propose two possible binding modes for this ligand based on flexible ligand docking calculations and show one of them to be analogues to the binding mode of a similar ligand, 2-BnTetAMPA. In long MD simulations, it was observed that transitions between both binding poses involve breaking and reforming the T686-E402 protein hydrogen bond. Simulating the ligand photo-isomerization process shows that the two possible configurations of the ligand azo-group have markedly different complex stabilities and equilibrium binding modes. A strong but slow protein response is observed after ligand configuration changes. This provides a microscopic foundation for the observed difference in ligand activity upon light-switching.

  6. Massively parallel decoding of mammalian regulatory sequences supports a flexible organizational model.

    Science.gov (United States)

    Smith, Robin P; Taher, Leila; Patwardhan, Rupali P; Kim, Mee J; Inoue, Fumitaka; Shendure, Jay; Ovcharenko, Ivan; Ahituv, Nadav

    2013-09-01

    Despite continual progress in the cataloging of vertebrate regulatory elements, little is known about their organization and regulatory architecture. Here we describe a massively parallel experiment to systematically test the impact of copy number, spacing, combination and order of transcription factor binding sites on gene expression. A complex library of ∼5,000 synthetic regulatory elements containing patterns from 12 liver-specific transcription factor binding sites was assayed in mice and in HepG2 cells. We find that certain transcription factors act as direct drivers of gene expression in homotypic clusters of binding sites, independent of spacing between sites, whereas others function only synergistically. Heterotypic enhancers are stronger than their homotypic analogs and favor specific transcription factor binding site combinations, mimicking putative native enhancers. Exhaustive testing of binding site permutations suggests that there is flexibility in binding site order. Our findings provide quantitative support for a flexible model of regulatory element activity and suggest a framework for the design of synthetic tissue-specific enhancers. PMID:23892608

  7. Inhibition of plasminogen activator inhibitor-1 binding to endocytosis receptors of the low density lipoprotein receptor family by a peptide isolated from a phage displayed library

    DEFF Research Database (Denmark)

    Jensen, Jan K.; Malmendal, Anders; Schiøtt, Birgit;

    2006-01-01

    (DVPCFGWCQDA) was determined by NMR. A binding site in the so-called flexible joint region of PAI-1 was suggested by molecular modelling and validated through binding studies with various competitors and site-directed mutagenesis of PAI-1. The peptide with an N-terminal biotin inhibited the binding of the u...

  8. Melanin-binding radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Packer, S; Fairchild, R G; Watts, K P; Greenberg, D; Hannon, S J

    1980-01-01

    The scope of this paper is limited to an analysis of the factors that are important to the relationship of radiopharmaceuticals to melanin. While the authors do not attempt to deal with differences between melanin-binding vs. melanoma-binding, a notable variance is assumed. (PSB)

  9. DNS BIND Server Configuration

    Directory of Open Access Journals (Sweden)

    Radu MARSANU

    2011-01-01

    Full Text Available After a brief presentation of the DNS and BIND standard for Unix platforms, the paper presents an application which has a principal objective, the configuring of the DNS BIND 9 server. The general objectives of the application are presented, follow by the description of the details of designing the program.

  10. Cognitive Flexibility in Obsessive Compulsive Disorder

    DEFF Research Database (Denmark)

    Jónsson, Hjalti; Salkovskis, Paul M.

    BT for problems such as OCD requires a level of cognitive flexibility (that is the ability to take a different perspective on ones problems). It could be argued that problems in set shifting (by neuropsychological tests) might underpin problems in this area. Two assessments were used (1: perception...... of cognitive flexibility was assessed by questionnaire 2: neuropsychological evaluation of set shifting). This study will recruit three groups: OCD patients, anxious and healthy controls. Cognitive flexibility is measured using modified version of the Cognitive Flexibility Scale (Martin & Rubin, 1995......) and neuropsychological measures of cognitive flexibility (Wisconsin Cart Sorting Test, Trail Making Test A/B, The Brixton Test). IN addition to the group comparison, the relationship between perceived flexibility, set shifting and psychopathology will be investigated. The implications of the findings for treatment...

  11. Alignment of flexible protein structures.

    Science.gov (United States)

    Shatsky, M; Fligelman, Z Y; Nussinov, R; Wolfson, H J

    2000-01-01

    We present two algorithms which align flexible protein structures. Both apply efficient structural pattern detection and graph theoretic techniques. The FlexProt algorithm simultaneously detects the hinge regions and aligns the rigid subparts of the molecules. It does it by efficiently detecting maximal congruent rigid fragments in both molecules and calculating their optimal arrangement which does not violate the protein sequence order. The FlexMol algorithm is sequence order independent, yet requires as input the hypothesized hinge positions. Due its sequence order independence it can also be applied to protein-protein interface matching and drug molecule alignment. It aligns the rigid parts of the molecule using the Geometric Hashing method and calculates optimal connectivity among these parts by graph-theoretic techniques. Both algorithms are highly efficient even compared with rigid structure alignment algorithms. Typical running times on a standard desktop PC (400 MHz) are about 7 seconds for FlexProt and about 1 minute for FlexMol.

  12. Mundari as a flexible language

    DEFF Research Database (Denmark)

    Hengeveld, Kees; Rijkhoff, Jan

    2005-01-01

    In this paper we intend to show that Mundari is one of the languages without distinct classes of verbs and nouns as far as its basic, non-derived vocabulary is concerned. Our contribution is organized as follows. Section 2 briefly presents a typology of parts-of-speech (PoS) systems, followed...... and verbs), thus disputing E&O’s claim that Mundari has clearly definable classes of verbs and nouns. The last section is concerned with a set of grammatical features which correlate with the presence of flexible lexemes in a language. It is concluded that Mundari displays all of the predicted features...... of a language that does not clearly distinguish between separate classes of nouns and verbs....

  13. Lifelong Open and Flexible Learning

    DEFF Research Database (Denmark)

    Bang, Jørgen

    2006-01-01

    for creating a synergy network in e-learning – eventually leading to a European Learning Space that supports virtual mobility of students, staff and courses, adds an e-dimension to the Bologa process and facilitates collaboration between universities and the corporate sector.......EADTU members are universities that are dedicated to off-campus target groups using distance teaching methods as well as associations consisting of universities with mainly mainstream on-campus students but also offering education for off-campus students. Consequently our focus is on Lifelong Open...... and Flexible (LOF) learning embracing characteristics as: open learning, distance learning, e-learning, online learning, open accessibility, multimedia support, virtual mobility, learning communities, dual mode (earn & learn) approaches, and the like.In my presentation I will focus on the EADTU strategies...

  14. Performance and Usability of Flexible Membrane Keyboards

    OpenAIRE

    Shin, Dong-Jae

    2005-01-01

    Recently, many full-sized keyboards have been designed to fold in various ways in an attempt to make them more transportable. The flexible membrane keyboard, one type of full sized keyboard, is unique because it is made from silicon rubber, thus it is fully flexible and water resistant. Although a number of flexible keyboard characteristics are the same as standard keyboards (i.e. key size, shape and spacing), key-switch and key clicking mechanisms are inherently different. Since there is ...

  15. MANAGEMENT OF PERFORMANCE PROCESSES: THE FLEXIBILITY CONCEPT

    OpenAIRE

    Benmoussa Rachid

    2010-01-01

    In this paper, we draw the thinking context for production process piloting according to flexibility approach. We apply a transversal process that defines the strategic purposes and deploys them on business processes and activities to define at the end action levers that permit reaching the fixed strategic targets. Flexibility concept is deployed through this process. We propose in this way concepts as volume, delay and variety flexibility at strategic level and concepts as unavailability, ef...

  16. Flexibility in 21st Century Power Systems

    Energy Technology Data Exchange (ETDEWEB)

    Cochran, J.; Miller, M.; Zinaman, O.; Milligan, M.; Arent, D.; Palmintier, B.; O' Malley, M.; Mueller, S.; Lannoye, E.; Tuohy, A.; Kujala, B.; Sommer, M.; Holttinen, H.; Kiviluoma, J.; Soonee, S. K.

    2014-05-01

    Flexibility of operation--the ability of a power system to respond to change in demand and supply--is a characteristic of all power systems. Flexibility is especially prized in twenty-first century power systems, with higher levels of grid-connected variable renewable energy (primarily, wind and solar). This paper summarizes the analytic frameworks that have emerged to measure this characteristic and distills key principles of flexibility for policy makers.

  17. Flexible Working Time Arrangements in Bulgaria

    OpenAIRE

    Beleva, Iskra

    2009-01-01

    The objective of this paper is to analyze the flexible working time arrangements in Bulgaria, using a life-course perspective. Two important features have to be outlined, namely: underdeveloped flexible forms of employment in the country, including working time arrangement, and lack of previous analysis on flexible working time arrangements from the angle of life-course perspective. The author describes the regulatory framework, collective agreements at national and company level as a frame w...

  18. Flexibility and Collusion with Imperfect Monitoring

    OpenAIRE

    Bigoni, Maria; Potters, Jan; Spagnolo, Giancarlo

    2012-01-01

    Flexibility - the ability to react swiftly to others' choices - facilitates collusion by reducing gains from defection before opponents react. Under imperfect monitoring, however, flexibility may also hinder collusion by inducing punishment after too few noisy signals. The combination of these forces predicts a non-monotonic relationship between flexibility and collusion. To test this subtle prediction we implement in the laboratory an indefinitely repeated Cournot game with noisy price infor...

  19. Does quality management drive labour flexibility?

    OpenAIRE

    Escrig Tena, Ana Belén; Bou Llusar, Juan Carlos; Roca Puig, Vicente; Beltrán Martín, Inmaculada

    2012-01-01

    This study aims to shed light on the contribution of quality management (QM) to labour flexibility by analysing the influence that QM has on internal and external labour flexibility. The study presents pioneer research in the empirical analysis of how QM impacts on labour flexibility. The hypotheses put forward are tested in an empirical study carried out on a sample of Spanish service companies. Structural equation modelling was used to analyse the data. The results indicate that QM is shown...

  20. Holographic sensing for control of flexible structures

    OpenAIRE

    Barsky, Michael Frederick

    1990-01-01

    A state feedback control system for flexible structures implemented using a holographic sensor and optical processor is presented. Real-time holography provides a mechanism for sensing the distributed shape of a broad class of one and two-dimensional flexible structures in a form that can be processed using fixed optics. The optical processing solves the spillover problem in the theory of the control of flexible structures. The optical processing also simplifies the computation allowing the s...

  1. Flexible depth of field photography.

    Science.gov (United States)

    Kuthirummal, Sujit; Nagahara, Hajime; Zhou, Changyin; Nayar, Shree K

    2011-01-01

    The range of scene depths that appear focused in an image is known as the depth of field (DOF). Conventional cameras are limited by a fundamental trade-off between depth of field and signal-to-noise ratio (SNR). For a dark scene, the aperture of the lens must be opened up to maintain SNR, which causes the DOF to reduce. Also, today's cameras have DOFs that correspond to a single slab that is perpendicular to the optical axis. In this paper, we present an imaging system that enables one to control the DOF in new and powerful ways. Our approach is to vary the position and/or orientation of the image detector during the integration time of a single photograph. Even when the detector motion is very small (tens of microns), a large range of scene depths (several meters) is captured, both in and out of focus. Our prototype camera uses a micro-actuator to translate the detector along the optical axis during image integration. Using this device, we demonstrate four applications of flexible DOF. First, we describe extended DOF where a large depth range is captured with a very wide aperture (low noise) but with nearly depth-independent defocus blur. Deconvolving a captured image with a single blur kernel gives an image with extended DOF and high SNR. Next, we show the capture of images with discontinuous DOFs. For instance, near and far objects can be imaged with sharpness, while objects in between are severely blurred. Third, we show that our camera can capture images with tilted DOFs (Scheimpflug imaging) without tilting the image detector. Finally, we demonstrate how our camera can be used to realize nonplanar DOFs. We believe flexible DOF imaging can open a new creative dimension in photography and lead to new capabilities in scientific imaging, vision, and graphics. PMID:21088319

  2. Technology modernization assessment flexible automation

    Energy Technology Data Exchange (ETDEWEB)

    Bennett, D.W.; Boyd, D.R.; Hansen, N.H.; Hansen, M.A.; Yount, J.A.

    1990-12-01

    The objectives of this report are: to present technology assessment guidelines to be considered in conjunction with defense regulations before an automation project is developed to give examples showing how assessment guidelines may be applied to a current project to present several potential areas where automation might be applied successfully in the depot system. Depots perform primarily repair and remanufacturing operations, with limited small batch manufacturing runs. While certain activities (such as Management Information Systems and warehousing) are directly applicable to either environment, the majority of applications will require combining existing and emerging technologies in different ways, with the special needs of depot remanufacturing environment. Industry generally enjoys the ability to make revisions to its product lines seasonally, followed by batch runs of thousands or more. Depot batch runs are in the tens, at best the hundreds, of parts with a potential for large variation in product mix; reconfiguration may be required on a week-to-week basis. This need for a higher degree of flexibility suggests a higher level of operator interaction, and, in turn, control systems that go beyond the state of the art for less flexible automation and industry in general. This report investigates the benefits and barriers to automation and concludes that, while significant benefits do exist for automation, depots must be prepared to carefully investigate the technical feasibility of each opportunity and the life-cycle costs associated with implementation. Implementation is suggested in two ways: (1) develop an implementation plan for automation technologies based on results of small demonstration automation projects; (2) use phased implementation for both these and later stage automation projects to allow major technical and administrative risk issues to be addressed. 10 refs., 2 figs., 2 tabs. (JF)

  3. Supermarket Defrost Cycles As Flexible Reserve

    DEFF Research Database (Denmark)

    Pedersen, Rasmus; Sloth, Christoffer; Wisniewski, Rafal;

    2015-01-01

    This work analyses how supermarket defrost cycles can be used as flexible reserve in a smart grid context. The consumption flexibility originates from being able to shift defrost cycles in time, while adhering to the underlying refrigeration systems constraints. It is shown how this time constrai......This work analyses how supermarket defrost cycles can be used as flexible reserve in a smart grid context. The consumption flexibility originates from being able to shift defrost cycles in time, while adhering to the underlying refrigeration systems constraints. It is shown how this time...

  4. Business Models for Power System Flexibility

    DEFF Research Database (Denmark)

    Boscan, Luis; Poudineh, Rahmatallah

    2016-01-01

    As intermittent, renewable resources gain more share in the generation mix, the need for power system flexibility increases more than ever. Parallel to this, technological change and the emergence of new players bringing about innovative solutions are boosting the development of flexibility-enabl...... business models will play an important role in ensuring sufficiency and efficiency of flexibility services.......-enabling business models, adding new activities to the existing supply chain. Ranging from technological to market-based innovation, this chapter reviews the latest developments in these emerging models. The main conclusion is that when flexibility becomes scarce in the system, new players with their innovative...

  5. Material challenge for flexible organic devices

    Directory of Open Access Journals (Sweden)

    Jay Lewis

    2006-04-01

    Full Text Available Outside of the active device layers, there are a variety of requisite functional layers in flexible organic electronic devices. Whether the application is in displays, lighting, integrated circuits, or photovoltaics, there are materials challenges in implementing flexible and/or organic devices into practical applications. We highlight two topics that are common to most flexible electronic technologies. First, we describe the difficulty in developing suitable permeation barriers on polymer substrates, the approaches being taken to solve this problem, and their current status. Second, we highlight the limited mechanical ruggedness of brittle inorganic films and present approaches for improving overall device flexibility.

  6. High Performance Electronics on Flexible Silicon

    KAUST Repository

    Sevilla, Galo T.

    2016-09-01

    Over the last few years, flexible electronic systems have gained increased attention from researchers around the world because of their potential to create new applications such as flexible displays, flexible energy harvesters, artificial skin, and health monitoring systems that cannot be integrated with conventional wafer based complementary metal oxide semiconductor processes. Most of the current efforts to create flexible high performance devices are based on the use of organic semiconductors. However, inherent material\\'s limitations make them unsuitable for big data processing and high speed communications. The objective of my doctoral dissertation is to develop integration processes that allow the transformation of rigid high performance electronics into flexible ones while maintaining their performance and cost. In this work, two different techniques to transform inorganic complementary metal-oxide-semiconductor electronics into flexible ones have been developed using industry compatible processes. Furthermore, these techniques were used to realize flexible discrete devices and circuits which include metal-oxide-semiconductor field-effect-transistors, the first demonstration of flexible Fin-field-effect-transistors, and metal-oxide-semiconductors-based circuits. Finally, this thesis presents a new technique to package, integrate, and interconnect flexible high performance electronics using low cost additive manufacturing techniques such as 3D printing and inkjet printing. This thesis contains in depth studies on electrical, mechanical, and thermal properties of the fabricated devices.

  7. A fast flexible docking method using an incremental construction algorithm.

    Science.gov (United States)

    Rarey, M; Kramer, B; Lengauer, T; Klebe, G

    1996-08-23

    We present an automatic method for docking organic ligands into protein binding sites. The method can be used in the design process of specific protein ligands. It combines an appropriate model of the physico-chemical properties of the docked molecules with efficient methods for sampling the conformational space of the ligand. If the ligand is flexible, it can adopt a large variety of different conformations. Each such minimum in conformational space presents a potential candidate for the conformation of the ligand in the complexed state. Our docking method samples the conformation space of the ligand on the basis of a discrete model and uses a tree-search technique for placing the ligand incrementally into the active site. For placing the first fragment of the ligand into the protein, we use hashing techniques adapted from computer vision. The incremental construction algorithm is based on a greedy strategy combined with efficient methods for overlap detection and for the search of new interactions. We present results on 19 complexes of which the binding geometry has been crystallographically determined. All considered ligands are docked in at most three minutes on a current workstation. The experimentally observed binding mode of the ligand is reproduced with 0.5 to 1.2 A rms deviation. It is almost always found among the highest-ranking conformations computed.

  8. Distal histidine conformational flexibility in dehaloperoxidase from Amphitrite ornata

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Zuxu; de Serrano, Vesna; Betts, Laurie; Franzen, Stefan; (NCSU); (UNC)

    2009-01-28

    The enzyme dehaloperoxidase (DHP) from the terebellid polychaete Amphitrite ornata is a heme protein which has a globin fold but can function as both a hemoglobin and a peroxidase. As a peroxidase, DHP is capable of converting 2,4,6-trihalophenols to the corresponding 2,6-dihaloquinones in the presence of hydrogen peroxide. As a hemoglobin, DHP cycles between the oxy and deoxy states as it reversibly binds oxygen for storage. Here, it is reported that the distal histidine, His55, exhibits conformational flexibility in the deoxy form and is consequently observed in two solvent-exposed conformations more than 9.5 {angstrom} away from the heme. These conformations are analogous to the open conformation of sperm whale myoglobin. The heme iron in deoxy ferrous DHP is five-coordinate and has an out-of-plane displacement of 0.25 {angstrom} from the heme plane. The observation of five-coordinate heme iron with His55 in a remote solvent-exposed conformation is consistent with the hypothesis that His55 interacts with heme iron ligands through hydrogen bonding in the closed conformation. Since His55 is also displaced by the binding of 4-iodophenol in an internal pocket, these results provide new insight into the correlation between heme iron ligation, molecular binding in the distal pocket and the conformation of the distal histidine in DHP.

  9. Pressure dissociation of integration host factor–DNA complexes reveals flexibility-dependent structural variation at the protein–DNA interface

    OpenAIRE

    Senear, Donald F.; Tretyachenko-Ladokhina, Vira; Opel, Michael L.; Aeling, Kimberly A.; G Wesley Hatfield; Franklin, Laurie M.; Darlington, Reuben C.; Alexander Ross, J. B.

    2007-01-01

    E. coli Integration host factor (IHF) condenses the bacterial nucleoid by wrapping DNA. Previously, we showed that DNA flexibility compensates for structural characteristics of the four consensus recognition elements associated with specific binding (Aeling et al., J. Biol. Chem. 281, 39236–39248, 2006). If elements are missing, high-affinity binding occurs only if DNA deformation energy is low. In contrast, if all elements are present, net binding energy is unaffected by deformation energy. ...

  10. The impact of enterprise systems on process flexibility and organisational flexibility

    Science.gov (United States)

    Qu, Wen Guang; Ding, Yajing; Shou, Yongyi; Zhou, Honggeng; Du, Hong

    2014-09-01

    In light of the current dynamic business environment, companies nowadays need to respond rapidly to changes. Companies often invest heavily in enterprise systems in the hope that these can improve their flexibility in coping with such changes. However, previous studies have shown that the impact of enterprise systems on flexibility can be either positive or negative. To resolve this inconsistency in the existing research, this paper suggests that a company's flexibility should be distinguished between process level and organisational level. Specifically, this paper proposes that enterprise systems will affect process flexibility negatively but affect organisational flexibility positively. The analysis results show that enterprise systems have different effects on process and organisational flexibility. Furthermore, industry clockspeed sets a boundary for the effect on process flexibility but not for that on organisational flexibility. Research and practical implications of this study are discussed.

  11. Stability and Sugar Recognition Ability of Ricin-Like Carbohydrate Binding Domains

    Energy Technology Data Exchange (ETDEWEB)

    Yao, Jianzhuang [ORNL; Nellas, Ricky B [ORNL; Glover, Mary M [ORNL; Shen, Tongye [ORNL

    2011-01-01

    Lectins are a class of proteins known for their novel binding to saccharides. Understanding this sugar recognition process can be crucial in creating structure-based designs of proteins with various biological roles. We focus on the sugar binding of a particular lectin, ricin, which has two -trefoil carbohydrate-binding domains (CRDs) found in several plant protein toxins. The binding ability of possible sites of ricin-like CRD has been puzzling. The apo and various (multiple) ligand-bound forms of the sugar-binding domains of ricin were studied by molecular dynamics simulations. By evaluating structural stability, hydrogen bond dynamics, flexibility, and binding energy, we obtained a detailed picture of the sugar recognition of the ricin-like CRD. Unlike what was previously believed, we found that the binding abilities of the two known sites are not independent of each other. The binding ability of one site is positively affected by the other site. While the mean positions of different binding scenarios are not altered significantly, the flexibility of the binding pockets visibly decreases upon multiple ligand binding. This change in flexibility seems to be the origin of the binding cooperativity. All the hydrogen bonds that are strong in the monoligand state are also strong in the double-ligand complex, although the stability is much higher in the latter form due to cooperativity. These strong hydrogen bonds in a monoligand state are deemed to be the essential hydrogen bonds. Furthermore, by examining the structural correlation matrix, the two domains are structurally one entity. Galactose hydroxyl groups, OH4 and OH3, are the most critical parts in both site 1 and site 2 recognition.

  12. Flexibility@Work 2013: yearly report on flexible labor and employment

    NARCIS (Netherlands)

    E. Berkhout; A. Heyma; J. Prins

    2013-01-01

    There is no clear evidence that the strong growth in the share of flexible labor relations between 2002 and 2007 points at a worldwide trend towards a larger share of flexible labor at the expense of traditional open-ended labor contracts. The growth in flexible labor varies too much between countri

  13. Magnetoelectric Nanocomposites for Flexible Electronics

    KAUST Repository

    Al-Nassar, Mohammed Y.

    2015-09-01

    Flexibility, low cost, versatility, miniaturization and multi-functionality are key aspects driving research and innovation in many branches of the electronics industry. With many anticipated emerging applications, like wearable, transparent and biocompatible devices, interest among the research community in pursuit for novel multifunctional miniaturized materials have been amplified. In this context, multiferroic polymer-based nanocomposites, possessing both ferroelectricity and ferromagnetism, are highly appealing. Most importantly, these nanocomposites possess tunable ferroelectric and ferromagnetic properties based on the parameters of their constituent materials as well as the magnetoelectric effect, which is the coupling between electric and magnetic properties. This tunability and interaction is a fascinating fundamental research field promising tremendous potential applications in sensors, actuators, data storage and energy harvesting. This dissertation work is devoted to the investigation of a new class of multiferroic polymer-based flexible nanocomposites, which exhibits excellent ferromagnetism and ferroelectricity simultaneously at room temperature, with the goal of understanding and optimizing the origin of their magnetoelectric coupling. The nanocomposites consist of high aspect ratio ferromagnetic nanowires (NWs) embedded inside a ferroelectric co-polymer, poly(vinylindene fluoride-trifluoroethylene), P(VDF-TrFE) matrix. First, electrochemical deposition of ferromagnetic NWs inside anodic aluminum oxide membranes is discussed. Characterization of electrodeposited iron, nickel and highly magnetostrictive iron-gallium alloy NWs was done using XRD, electron and magnetic force microscopy. Second, different nanocomposite films have been fabricated by means of spin coating and drop casting techniques. The effect of incorporation of NWs inside the ferroelectric polymer on its electroactive phase is discussed. The remanent and saturation polarization as well

  14. Cloud flexibility using DIRAC interware

    International Nuclear Information System (INIS)

    Communities of different locations are running their computing jobs on dedicated infrastructures without the need to worry about software, hardware or even the site where their programs are going to be executed. Nevertheless, this usually implies that they are restricted to use certain types or versions of an Operating System because either their software needs an definite version of a system library or a specific platform is required by the collaboration to which they belong. On this scenario, if a data center wants to service software to incompatible communities, it has to split its physical resources among those communities. This splitting will inevitably lead to an underuse of resources because the data centers are bound to have periods where one or more of its subclusters are idle. It is, in this situation, where Cloud Computing provides the flexibility and reduction in computational cost that data centers are searching for. This paper describes a set of realistic tests that we ran on one of such implementations. The test comprise software from three different HEP communities (Auger, LHCb and QCD phenomelogists) and the Parsec Benchmark Suite running on one or more of three Linux flavors (SL5, Ubuntu 10.04 and Fedora 13). The implemented infrastructure has, at the cloud level, CloudStack that manages the virtual machines (VM) and the hosts on which they run, and, at the user level, the DIRAC framework along with a VM extension that will submit, monitorize and keep track of the user jobs and also requests CloudStack to start or stop the necessary VM's. In this infrastructure, the community software is distributed via the CernVM-FS, which has been proven to be a reliable and scalable software distribution system. With the resulting infrastructure, users are allowed to send their jobs transparently to the Data Center. The main purpose of this system is the creation of flexible cluster, multiplatform with an scalable method for software distribution for

  15. Cloud flexibility using DIRAC interware

    Science.gov (United States)

    Fernandez Albor, Víctor; Seco Miguelez, Marcos; Fernandez Pena, Tomas; Mendez Muñoz, Victor; Saborido Silva, Juan Jose; Graciani Diaz, Ricardo

    2014-06-01

    Communities of different locations are running their computing jobs on dedicated infrastructures without the need to worry about software, hardware or even the site where their programs are going to be executed. Nevertheless, this usually implies that they are restricted to use certain types or versions of an Operating System because either their software needs an definite version of a system library or a specific platform is required by the collaboration to which they belong. On this scenario, if a data center wants to service software to incompatible communities, it has to split its physical resources among those communities. This splitting will inevitably lead to an underuse of resources because the data centers are bound to have periods where one or more of its subclusters are idle. It is, in this situation, where Cloud Computing provides the flexibility and reduction in computational cost that data centers are searching for. This paper describes a set of realistic tests that we ran on one of such implementations. The test comprise software from three different HEP communities (Auger, LHCb and QCD phenomelogists) and the Parsec Benchmark Suite running on one or more of three Linux flavors (SL5, Ubuntu 10.04 and Fedora 13). The implemented infrastructure has, at the cloud level, CloudStack that manages the virtual machines (VM) and the hosts on which they run, and, at the user level, the DIRAC framework along with a VM extension that will submit, monitorize and keep track of the user jobs and also requests CloudStack to start or stop the necessary VM's. In this infrastructure, the community software is distributed via the CernVM-FS, which has been proven to be a reliable and scalable software distribution system. With the resulting infrastructure, users are allowed to send their jobs transparently to the Data Center. The main purpose of this system is the creation of flexible cluster, multiplatform with an scalable method for software distribution for several

  16. Modelling Flexible Pavement Response and Performance

    DEFF Research Database (Denmark)

    Ullidtz, Per

    This textbook is primarily concerned with models for predicting the future condition of flexible pavements, as a function of traffic loading, climate, materials, etc., using analytical-empirical methods.......This textbook is primarily concerned with models for predicting the future condition of flexible pavements, as a function of traffic loading, climate, materials, etc., using analytical-empirical methods....

  17. Relation of adipose tissue to metabolic flexibility

    OpenAIRE

    Sparks, Lauren M.; Ukropcova, Barbara; Smith, Jana; Pasarica, Magdalena; Hymel, David; Xie, Hui; Bray, George A.; Miles, John M.; Smith, Steven R.

    2008-01-01

    Metabolic flexibility is the capacity for skeletal muscle to shift reliance between lipids and glucose during fasting or in response to insulin. We hypothesized that body fat, adipose tissue characteristics, e.g. larger adipocytes, presence of inflammatory gene markers and impaired suppression of non-esterified fatty acids (NEFAs) during insulin infusion might be related to metabolic flexibility.

  18. CHANGE MANAGEMENT ESSENTIALS TO MANAGE BUSINESS FLEXIBILITY

    OpenAIRE

    Cãtãlin Cristian BABALÂC; Mihaela UDÃ

    2014-01-01

    The present paper has as objective to introduce essential concepts that stand as basis for change and risk management, having a direct influence on flexibility. The competitive advantage represented by the company flexibility either if it is achieved by technology or with the help of human factor follows a path characterized by risk and possible resistance to what is the normal state.

  19. Studies of a flexible heliac configuration

    International Nuclear Information System (INIS)

    This paper documents a detailed study of the Flexible Heliac configuration. The remarkable flexibility of this device - which allows variation of the rotational transform, shear, and magnetic well depth over a relatively wide range - is described. Engineering considerations of error fields, finite cross-section conductors, and plasma coil clearances are also discussed

  20. Flexible benefit plans in Dutch organisations

    NARCIS (Netherlands)

    Hillebrink, C.

    2006-01-01

    Flexible benefit plans give employees a greater say over the composition of their benefits than traditional Dutch benefit plans. These arrangements developed in a time of further individualisation, increasing flexibility in the workplace, and a tight labour market in the Netherlands. By giving emplo

  1. Designing for flexibility in the traditional university.

    NARCIS (Netherlands)

    Collis, Betty; Boer, de Wim

    2005-01-01

    Instructors in traditional universities are expected to respond to the needs of an increasingly diverse student body by making more flexibility available in their courses. Based on a systematic analysis of flexibility options, various tools to help instructors in the design of their course Web envir

  2. "Flexibility", Community and Making Parents Responsible

    Science.gov (United States)

    McGowan, Wayne S.

    2005-01-01

    This article draws on Foucault's concept of governmentality to explore how recent political moves to legalise "flexibility" mobilises education authorities to make "community" a technical means of achieving the political objective of schooling the child. I argue that "flexibility" in this sense is a neo-liberal strategy that shifts relations…

  3. Role of Flexibility in Sustainable Port Development

    NARCIS (Netherlands)

    Taneja, P.; Vellinga, T.; Ros, R.

    2012-01-01

    Sustainability has become a high profile objective in all aspects of our lives, including the development of our infrastructures. Flexibility can enhance sustainability endeavors, yet its contribution is not clear to most. In this paper we investigate the role of flexibility in sustainable port deve

  4. Semiconductor films on flexible iridium substrates

    Science.gov (United States)

    Goyal, Amit

    2005-03-29

    A laminate semiconductor article includes a flexible substrate, an optional biaxially textured oxide buffer system on the flexible substrate, a biaxially textured Ir-based buffer layer on the substrate or the buffer system, and an epitaxial layer of a semiconductor. Ir can serve as a substrate with an epitaxial layer of a semiconductor thereon.

  5. Quality and workflow integration in flexible manufacturing

    NARCIS (Netherlands)

    Dam, ten D.C.

    2012-01-01

    In recognising the relevance of production networks and flexible manufacturing, CNC Worknet aims to be a company that approaches the new era of flexible manufacturing by developing a novel business model that combines the technologies of e-Business with production networks. This business model is ba

  6. SHBG (Sex Hormone Binding Globulin)

    Science.gov (United States)

    ... as: Testosterone-estrogen Binding Globulin; TeBG Formal name: Sex Hormone Binding Globulin Related tests: Testosterone , Free Testosterone, ... I should know? How is it used? The sex hormone binding globulin (SHBG) test may be used ...

  7. Flexible Ultrasonic Phased-Array Probe

    Institute of Scientific and Technical Information of China (English)

    施克仁; 阙开良; 郭大勇

    2004-01-01

    In ultrasonic phased-array testing, most probes are rigid with fixed elements. However, when testing a cambered piece, a rigid probe cannot be used directly, but an ultrasonic chock or coupling media must be used, which adds cost and reduces the accuracy. The objective of this research was to improve the tests of cambered pieces. A flexible ultrasonic phased-array probe was developed to do the flexible phased-array testing. The key technologies in the flexible phased-array probe include the probe design and the phased-array control. A new method was developed to design the flexible probe according to the curvature of the piece and the test depth. The method includes the calculation of the element's height (he), the relative rotation angle ((e), the distance between the adjoining elements (de), and the element's effective testing range. A flexible ultrasonic phased-array probe has been developed using this method.

  8. STARD4 Membrane Interactions and Sterol Binding.

    Science.gov (United States)

    Iaea, David B; Dikiy, Igor; Kiburu, Irene; Eliezer, David; Maxfield, Frederick R

    2015-08-01

    The steroidogenic acute regulatory protein-related lipid transfer (START) domain family is defined by a conserved 210-amino acid sequence that folds into an α/β helix-grip structure. Members of this protein family bind a variety of ligands, including cholesterol, phospholipids, sphingolipids, and bile acids, with putative roles in nonvesicular lipid transport, metabolism, and cell signaling. Among the soluble START proteins, STARD4 is expressed in most tissues and has previously been shown to transfer sterol, but the molecular mechanisms of membrane interaction and sterol binding remain unclear. In this work, we use biochemical techniques to characterize regions of STARD4 and determine their role in membrane interaction and sterol binding. Our results show that STARD4 interacts with anionic membranes through a surface-exposed basic patch and that introducing a mutation (L124D) into the Omega-1 (Ω1) loop, which covers the sterol binding pocket, attenuates sterol transfer activity. To gain insight into the attenuating mechanism of the L124D mutation, we conducted structural and biophysical studies of wild-type and L124D STARD4. These studies show that the L124D mutation reduces the conformational flexibility of the protein, resulting in a diminished level of membrane interaction and sterol transfer. These studies also reveal that the C-terminal α-helix, and not the Ω1 loop, partitions into the membrane bilayer. On the basis of these observations, we propose a model of STARD4 membrane interaction and sterol binding and release that requires dynamic movement of both the Ω1 loop and membrane insertion of the C-terminal α-helix.

  9. Structural Basis for Binding of RNA and Cofactor by a KsgA Methyltransferase

    Energy Technology Data Exchange (ETDEWEB)

    Tu, Chao; Tropea, Joseph E.; Austin, Brian P.; Court, Donald L.; Waugh, David S.; Ji, Xinhua; (NCI)

    2009-03-27

    Among methyltransferases, KsgA and the reaction it catalyzes are conserved throughout evolution. However, the specifics of substrate recognition by the enzyme remain unknown. Here we report structures of Aquifex aeolicus KsgA, in its ligand-free form, in complex with RNA, and in complex with both RNA and S-adenosylhomocysteine (SAH, reaction product of cofactor S-adenosylmethionine), revealing critical structural information on KsgA-RNA and KsgA-SAH interactions. Moreover, the structures show how conformational changes that occur upon RNA binding create the cofactor-binding site. There are nine conserved functional motifs (motifs IVIII and X) in KsgA. Prior to RNA binding, motifs I and VIII are flexible, each exhibiting two distinct conformations. Upon RNA binding, the two motifs become stabilized in one of these conformations, which is compatible with the binding of SAH. Motif X, which is also stabilized upon RNA binding, is directly involved in the binding of SAH.

  10. Mechanical flexible joint design document

    Science.gov (United States)

    Daily, Vic

    1993-01-01

    The purpose of this report is to document the status of the Mechanical Flexible Joint (MFJ) Design Subtask with the intent of halting work on the design. Recommendations for future work is included in the case that the task is to be resumed. The MFJ is designed to eliminate two failure points from the current flex joint configuration, the inner 'tripod configuration' and the outer containment jacket. The MFJ will also be designed to flex 13.5 degrees and have three degrees of freedom. By having three degrees of freedom, the MFJ will allow the Low Pressure Fuel Duct to twist and remove the necessity to angulate the full 11 degrees currently required. The current flex joints are very labor intensive and very costly and a simple alternative is being sought. The MFJ is designed with a greater angular displacement, with three degrees of freedom, to reside in the same overall envelope, to meet weight constraints of the current bellows, to be compatible with cryogenic fuel and oxidizers, and also to be man-rated.

  11. Lactate Sensors on Flexible Substrates

    Science.gov (United States)

    Yang, Xuesong; Fu, Timothy; Kota, Pavan Kumar; Tjia, Maggie; Nguyen, Cuong Manh; Chiao, Jung-Chih

    2016-01-01

    Lactate detection by an in situ sensor is of great need in clinical medicine, food processing, and athletic performance monitoring. In this paper, a flexible, easy to fabricate, and low-cost biosensor base on lactate oxidase is presented. The fabrication processes, including metal deposition, sol-gel IrOx deposition, and drop-dry enzyme loading method, are described in detail. The loaded enzyme was examined by scanning electron microscopy. Cyclic voltammetry was used to characterize the sensors. Durability, sensibility, and selectivity of the biosensors were examined. The comparison for different electrode sizes and different sensing film materials was conducted. The sensor could last for four weeks with an average surface area normalized sensitivity of 950 nA/(cm2 mM) and 9250 nA/(cm2 mM) for Au-based electrodes, and IrOx-modified electrodes respectively, both with an electrode size of 100 × 50 μm. The self-referencing method to record noises simultaneously with the working electrode greatly improved sensor sensitivity and selectivity. The sensor showed little response to interference chemicals, such as glutamate and dopamine. PMID:27657147

  12. Surface-grafted polymer-assisted electroless deposition of metals for flexible and stretchable electronics.

    Science.gov (United States)

    Liu, Xuqing; Zhou, Xuechang; Li, Yi; Zheng, Zijian

    2012-05-01

    Surface-grafted polymers, that is, ultrathin layers of polymer coating covalently tethered to a surface, can serve as a particularly promising nanoplatform for electroless deposition (ELD) of metal thin films and patterned structures. Such polymers consist of a large number of well-defined binding sites for highly efficient and selective uptake of ELD catalysts. Moreover, the polymer chains provide flexible 3D network structures to trap the electrolessly deposited metal particles, leading to strong metal-substrate adhesion. In the past decade, surface-grafted polymers have been demonstrated as efficient nanoplatforms for fabricating durable and high-performance metal coatings by ELD on plastic substrates for applications in flexible and stretchable electronics. This focus review summarizes these recent advances, with a particular focus on applications in polymeric flexible and stretchable substrates. An outlook on the future challenges and opportunities in this field is given at the end of this paper. PMID:22392811

  13. Workplace flexibility: from research to action.

    Science.gov (United States)

    Galinsky, Ellen; Sakai, Kelly; Wigton, Tyler

    2011-01-01

    Ellen Galinsky, Kelly Sakai, and Tyler Wigton explore the "time famine" among American workers-the continuing sense among employees of not having enough time to manage the multiple responsibilities of work and personal and family life. Noting that large shares of U.S. employees report feeling the need for greater workplace flexibility to enable them to take better care of family responsibilities, the authors examine a large-scale community-engagement initiative to increase workplace flexibility voluntarily. Using the 2008 National Study of the Changing Workforce as a primary source of data, the authors begin with an overview of the prevalence of flexibility in today's American workplace. They track which categories of employees have access to various flexibility options, as well as the extent to which employees with access to various types of flexibility use those options. Findings from the study indicate that the majority of employees want flexibility but that access to it varies, with more advantaged employees--those who are well educated, have high salaries, and work full time, for example--being doubly advantaged in having greater access to flexibility. A number of employers, say the authors, tend to be skeptical of the value of workplace flexibility and to fear that employees will abuse it if it is offered. But the study data reveal that most employees use flexibility quite conservatively. When the authors use their nationally representative data set to investigate correlations between access to workplace flexibility and a range of workplace outcomes especially valued by employers--employee engagement, job satisfaction, retention, and health--they find that employers as well as employees can benefit from flexibility. Finally, the authors discuss When Work Works, a large, national community-based initiative under way since 2003 to increase voluntary adoption of workplace flexibility. The authors detail the conceptual basis of the project's design, noting its

  14. Inter-vertebral flexibility of the ostrich neck: implications for estimating sauropod neck flexibility.

    Directory of Open Access Journals (Sweden)

    Matthew J Cobley

    Full Text Available The flexibility and posture of the neck in sauropod dinosaurs has long been contentious. Improved constraints on sauropod neck function will have major implications for what we know of their foraging strategies, ecology and overall biology. Several hypotheses have been proposed, based primarily on osteological data, suggesting different degrees of neck flexibility. This study attempts to assess the effects of reconstructed soft tissues on sauropod neck flexibility through systematic removal of muscle groups and measures of flexibility of the neck in a living analogue, the ostrich (Struthio camelus. The possible effect of cartilage on flexibility is also examined, as this was previously overlooked in osteological estimates of sauropod neck function. These comparisons show that soft tissues are likely to have limited the flexibility of the neck beyond the limits suggested by osteology alone. In addition, the inferred presence of cartilage, and varying the inter-vertebral spacing within the synovial capsule, also affect neck flexibility. One hypothesis proposed that flexibility is constrained by requiring a minimum overlap between successive zygapophyses equivalent to 50% of zygapophyseal articular surface length (ONP50. This assumption is tested by comparing the maximum flexibility of the articulated cervical column in ONP50 and the flexibility of the complete neck with all tissues intact. It is found that this model does not adequately convey the pattern of flexibility in the ostrich neck, suggesting that the ONP50 model may not be useful in determining neck function if considered in isolation from myological and other soft tissue data.

  15. An assessment of the EU proposal for ceilings on the use of Kyoto flexibility mechanisms

    OpenAIRE

    Zhang, ZhongXiang

    2000-01-01

    The Kyoto Protocol is the first international environmental agreement that sets legally binding greenhouse gas emissions targets and timetables for Annex I countries. It incorporates emissions trading, joint implementation and the clean development mechanism. Because each of the Articles defining the three flexibility mechanisms carries wording that the use of the mechanism must be supplemental to domestic actions, the supplementarity provisions have been the focus of the international climat...

  16. Extracellular-regulated kinase 2 is activated by the enhancement of hinge flexibility.

    OpenAIRE

    Sours, Kevin M.; Xiao,Yao; Ahn, Natalie G.

    2014-01-01

    Protein motions underlie conformational and entropic contributions to enzyme catalysis; however, relatively little is known about the ways in which this occurs. Studies of the mitogen-activated protein kinase ERK2 (extracellular-regulated protein kinase 2) by hydrogen-exchange mass spectrometry suggest that activation enhances backbone flexibility at the linker between N- and C-terminal domains while altering nucleotide binding mode. Here, we address the hypothesis that enhanced backbone flex...

  17. Probabilistic Model to Treat Flexibility in Molecular Contacts

    CERN Document Server

    Hakulinen, Riku

    2016-01-01

    Evaluating accessible conformational space is computationally expensive and thermal motions are partly neglected in computer models of molecular interactions. This produces error into the estimates of binding strength. We introduce a method for modelling interactions so that structural flexibility is inherently taken into account. It has a statistical model for 3D properties of 'nonlocal' contacts and a physics based description of 'local' interactions, based on mechanical torque. The form of the torque barrier is derived using a representation of the local electronic structure, which is presumed to improve transferability, compared to traditional force fields. The nonlocal contacts are more distant than 1-4 interactions and Target-atoms are represented by 3D probability densities. Probability mass quantifies strength of contact and is calculated as an overlap integral. Repulsion is described by negative probability density, allowing probability mass to be used as the descriptor of contact preference. As a re...

  18. Fast antibody fragment motion: flexible linkers act as entropic spring.

    Science.gov (United States)

    Stingaciu, Laura R; Ivanova, Oxana; Ohl, Michael; Biehl, Ralf; Richter, Dieter

    2016-01-01

    A flexible linker region between three fragments allows antibodies to adjust their binding sites to an antigen or receptor. Using Neutron Spin Echo Spectroscopy we observed fragment motion on a timescale of 7 ns with motional amplitudes of about 1 nm relative to each other. The mechanistic complexity of the linker region can be described by a spring model with Brownian motion of the fragments in a harmonic potential. Displacements, timescale, friction and force constant of the underlying dynamics are accessed. The force constant exhibits a similar strength to an entropic spring, with friction of the fragment matching the unbound state. The observed fast motions are fluctuations in pre-existing equilibrium configurations. The Brownian motion of domains in a harmonic potential is the appropriate model to examine functional hinge motions dependent on the structural topology and highlights the role of internal forces and friction to function. PMID:27020739

  19. The balance of flexibility and rigidity in the active site residues of hen egg white lysozyme

    Institute of Scientific and Technical Information of China (English)

    Qi Jian-Xun; Jiang Fan

    2011-01-01

    The crystallographic temperature factors (B factor) of individual atoms contain important information about the thermal motion of the atoms in a macromolecule. Previously the theory of flexibility of active site has been established based on the observation that the enzyme activity is sensitive to low concentration denaturing agents. It has been found that the loss of enzyme activity occurs well before the disruption of the three-dimensional structural scaffold of the enzyme. To test the theory of conformational flexibility of enzyme active site, crystal structures were perturbed by soaking in low concentration guanidine hydrochloride solutions. It was found that many lysozyme crystals tested could still diffract until the concentration of guanidine hydrochloride reached 3 M. It was also found that the B factors averaged over individually collected data sets were more accurate. Thus it suggested that accurate measurement of crystal temperature factors could be achieved for medium-high or even medium resolution crystals by averaging over multiple data sets. Furthermore, we found that the correctly predicted active sites included not only the more flexible residues, but also some more rigid residues. Both the flexible and the rigid residues in the active site played an important role in forming the active site residue network, covering the majority of the substrate binding residues. Therefore, this experimental prediction method may be useful for characterizing the binding site and the function of a protein, such as drug targeting.

  20. Flexible time domain averaging technique

    Science.gov (United States)

    Zhao, Ming; Lin, Jing; Lei, Yaguo; Wang, Xiufeng

    2013-09-01

    Time domain averaging(TDA) is essentially a comb filter, it cannot extract the specified harmonics which may be caused by some faults, such as gear eccentric. Meanwhile, TDA always suffers from period cutting error(PCE) to different extent. Several improved TDA methods have been proposed, however they cannot completely eliminate the waveform reconstruction error caused by PCE. In order to overcome the shortcomings of conventional methods, a flexible time domain averaging(FTDA) technique is established, which adapts to the analyzed signal through adjusting each harmonic of the comb filter. In this technique, the explicit form of FTDA is first constructed by frequency domain sampling. Subsequently, chirp Z-transform(CZT) is employed in the algorithm of FTDA, which can improve the calculating efficiency significantly. Since the signal is reconstructed in the continuous time domain, there is no PCE in the FTDA. To validate the effectiveness of FTDA in the signal de-noising, interpolation and harmonic reconstruction, a simulated multi-components periodic signal that corrupted by noise is processed by FTDA. The simulation results show that the FTDA is capable of recovering the periodic components from the background noise effectively. Moreover, it can improve the signal-to-noise ratio by 7.9 dB compared with conventional ones. Experiments are also carried out on gearbox test rigs with chipped tooth and eccentricity gear, respectively. It is shown that the FTDA can identify the direction and severity of the eccentricity gear, and further enhances the amplitudes of impulses by 35%. The proposed technique not only solves the problem of PCE, but also provides a useful tool for the fault symptom extraction of rotating machinery.

  1. Flexible Learning in an Information Society

    Directory of Open Access Journals (Sweden)

    Edited by Badrul H. Khan and Reviewed by Dr. Adile Aşkım Kurt

    2007-01-01

    Full Text Available This book was edited by, Badrul H. Khan, Director of the Educational Technology Leadership graduate cohort program at The George Washington University, and published by Information Science Publishing an imprint of Idea Group Inc.The information age has brought about many ways for educators to help their students learn, creating an atmosphere where the learners desire flexibility in the way they learn. With the increasing use of variety of approaches for learning, students’ preferences are changing from wanting to be taught mostly in lectures or direct training sessions to wanting increased flexibility. Students expect on demand anytime/anywhere high-quality learning environments with good support services. They want increased flexibility.This book uses a flexible learning framework to create meaningful flexible learning environments. This framework consists of eight factors; institutional, management, technological, pedagogical, ethical, interface design, resource support, and evaluation. This book presents a broad understanding of the emerging field of flexible learning and provides guidance in creating these environments. The book has thirty chapters, encompass various critical issues dealing with one or more categories of the flexible learning framework and offer a variety of points of view on these issues.

  2. ESF [Exploratory Shaft Facility] flexibility analysis

    International Nuclear Information System (INIS)

    This report directs that uncertainty allowances be included within the ESF facilities. The recommendations herein developed are intended as input to Title II Design criteria. Flexibility is measured first by lineal ft of drift, and then by hoisting rate and capacity of supporting utilities and services. A defined probability of need shows an extra 10,000 ft of drift for the first level of flexibility responding to testing and operations, and over 60,000 ft of drift for the second level of flexibility which recognizes possible need for perimeter drifting to investigate geologic stratigraphy. Observing there will be time constraints, a single shaft muck hoisting rate up to 170 to 250 tons per hour is recommended. The potential hoisting rate recommended for flexibility should be satisfied by a hoist approximately equivalent to, or conveniently upgraded from those being considered for sinking and construction, or 1000 horsepower. The cost of flexibility is limited to engineering planning and design (mostly conceptual) which makes later expansion achievable, and to selected items for initial construction where later upgrading would be impractical, impossible, or very costly. The cost is fixed to the level of flexibility and does not vary with excavated footage. The incremental margin is only a small fraction of the additional footage made available. Flexibility presents a strategy and not a position of design or technology. Examples used in this report are intended to be illustrative only, and not to lead design or cost estimates. 7 tabs

  3. Computational study of ligand binding in lipid transfer proteins: Structures, interfaces, and free energies of protein-lipid complexes

    OpenAIRE

    Fernandez Pacios, Luis; Gomez Casado, Cristina; Tordesillas Villuendas, Leticia; Palacín Gómez, Aranzazu; Sanchez-Monge Laguna De Rins, Maria Rosa; Díaz Perales, Araceli

    2012-01-01

    Plant nonspecific lipid transfer proteins (nsLTPs) bind a wide variety of lipids, which allows them to perform disparate functions. Recent reports on their multifunctionality in plant growth processes have posed new questions on the versatile binding abilities of these proteins. The lack of binding specificity has been customarily explained in qualitative terms on the basis of a supposed structural flexibility and nonspecificity of hydrophobic protein-ligand interactions. We present here a co...

  4. Cognitive flexibility predicts early reading skills.

    Directory of Open Access Journals (Sweden)

    Pascale eColé

    2014-06-01

    Full Text Available An important aspect of learning to read is efficiency in accessing different kinds of linguistic information (orthographic, phonological and semantic about written words. The present study investigates whether, in addition to the integrity of such linguistic skills, early progress in reading may require a degree of cognitive flexibility in order to manage the coordination of this information effectively. Our study will look for evidence of a link between flexibility and both word reading and passage reading comprehension, and examine whether any such link involves domain-general or reading-specific flexibility. As the only previous support for a predictive relationship between flexibility and early reading comes from studies of reading comprehension in the opaque English orthography, another possibility is that this relationship may be largely orthography-dependent, only coming into play when mappings between representations are complex and polyvalent. To investigate these questions, sixty second-graders learning to read the more transparent French orthography were presented with two multiple classification tasks involving reading-specific cognitive flexibility (based on words and non-specific flexibility (based on pictures. Reading skills were assessed by word reading, pseudo-word decoding and passage reading comprehension measures. Flexibility was found to contribute significant unique variance to passage reading comprehension even in the less opaque French orthography. More interestingly, the data also show that flexibility is critical in accounting for one of the core components of reading comprehension, namely, the reading of words in isolation. Finally, the results crucially constrain the debate over whether flexibility has to be reading-specific to be critically involved in reading.

  5. Flexible Molybdenum Electrodes towards Designing Affinity Based Protein Biosensors.

    Science.gov (United States)

    Kamakoti, Vikramshankar; Panneer Selvam, Anjan; Radha Shanmugam, Nandhinee; Muthukumar, Sriram; Prasad, Shalini

    2016-01-01

    Molybdenum electrode based flexible biosensor on porous polyamide substrates has been fabricated and tested for its functionality as a protein affinity based biosensor. The biosensor performance was evaluated using a key cardiac biomarker; cardiac Troponin-I (cTnI). Molybdenum is a transition metal and demonstrates electrochemical behavior upon interaction with an electrolyte. We have leveraged this property of molybdenum for designing an affinity based biosensor using electrochemical impedance spectroscopy. We have evaluated the feasibility of detection of cTnI in phosphate-buffered saline (PBS) and human serum (HS) by measuring impedance changes over a frequency window from 100 mHz to 1 MHz. Increasing changes to the measured impedance was correlated to the increased dose of cTnI molecules binding to the cTnI antibody functionalized molybdenum surface. We achieved cTnI detection limit of 10 pg/mL in PBS and 1 ng/mL in HS medium. The use of flexible substrates for designing the biosensor demonstrates promise for integration with a large-scale batch manufacturing process. PMID:27438863

  6. A flexible self-advancing support

    Energy Technology Data Exchange (ETDEWEB)

    Kulakov, V.N.; Kirilin, V.S.; Mishin, P.M.; Ororelkov, G.F.

    1983-01-01

    The purpose of this invention is to increase the operational reliability of the supports by providing self-advancing in a particular direction. This is achieved by an arrangement where the flexible self-advancing support is equipped with flexible attachments, one set of ends of which are fastened to the upper spans; the powered elements are manufactured as hydraulic jacks whose cylinders are hinged to the stope ends of the guides to allow for interaction with the end pneumatic cylinders, while the rods are coupled to the free ends of the flexible attachments using support plates with aprons.

  7. Flexible flatfoot in children and adolescents

    OpenAIRE

    Mosca, Vincent S.

    2010-01-01

    Flexible flatfoot is a normal foot shape that is present in most infants and many adults. The arch elevates spontaneously in most children during the first decade of life. There is no evidence that a longitudinal arch can be created in a child’s foot by any external forces or devices. Flexible flatfoot with a short Achilles tendon, in contrast to simple flexible flatfoot, is known to cause pain and disability in some adolescents and adults. Joint-preserving, deformity-correcting surgery is in...

  8. Damping Properties of Flexible Epoxy Resin

    Institute of Scientific and Technical Information of China (English)

    WANG Xiang; LIU Hanxing; OUYANG Shixi

    2008-01-01

    Amino-terminated polyethers and amino-terminated polyurethane were used as curing agent to cure the epoxy resin together and get a series of cured products. The damping properties of the composites were studied by DMA test at different measurement frequencies. Damping mechanical tests show that the flexible epoxy resin has higher loss factor than common epoxy. The highest loss factor reaches 1.57. Also the height and position of loss factor peak of the flexible epoxy resin varies by changing the content of amino-terminated polyethers. Results shows that the flexible epoxy resin can be used as damping polymer materials at room temperature or in common frequency range.

  9. Probabilistic Quantification of Potentially Flexible Residential Demand

    DEFF Research Database (Denmark)

    Kouzelis, Konstantinos; Mendaza, Iker Diaz de Cerio; Bak-Jensen, Birgitte

    2014-01-01

    The balancing of power systems with high penetration of renewable energy is a serious challenge to be faced in the near future. One of the possible solutions, recently capturing a lot of attention, is demand response. Demand response can only be achieved by power consumers holding loads which allow...... them to modify their normal power consumption pattern, namely flexible consumers. However flexibility, despite being constantly mentioned, is usually not properly defined and even rarer quantified. This manuscript introduces a methodology to identify and quantify potentially flexible demand...

  10. Ultrabarrier Flexible Substrates for Flat Panel Displays

    Energy Technology Data Exchange (ETDEWEB)

    Burrows, Paul E.; Graff, Gordon L.; Gross, Mark E.; Martin, Peter M.; Shi, Ming-Kun; Hall, Michael G.; Mast, Eric S.; Bonham, Charles C.; Bennett, Wendy D.; Sullivan, Michael B.

    2001-05-01

    We describe a flexible, transparent plastic substrate for flat panel display applications. Using roll-coating techniques, we apply a composite thin film barrier to commercially available polymers, which restricts moisture and oxygen permeation to undetectable levels. The barrier film can be capped with a thin film of transparent conductive oxide in the same roll-coater, yielding an engineered substrate (Barix™) for next generation, rugged, lightweight or flexible displays. The substrate is sufficiently impermeable to moisture and oxygen for application to moisture-sensitive display applications, such as organic light emitting displays (OLEDs). This enables, for the first time, lightweight and flexible emissive organic displays.

  11. Rigidity and flexibility of biological networks

    CERN Document Server

    Gaspar, Merse E

    2012-01-01

    The network approach became a widely used tool to understand the behaviour of complex systems in the last decade. We start from a short description of structural rigidity theory. A detailed account on the combinatorial rigidity analysis of protein structures, as well as local flexibility measures of proteins and their applications in explaining allostery and thermostability is given. We also briefly discuss the network aspects of cytoskeletal tensegrity. Finally, we show the importance of the balance between functional flexibility and rigidity in protein-protein interaction, metabolic, gene regulatory and neuronal networks. Our summary raises the possibility that the concepts of flexibility and rigidity can be generalized to all networks.

  12. Rigidity and flexibility of biological networks.

    Science.gov (United States)

    Gáspár, Merse E; Csermely, Peter

    2012-11-01

    The network approach became a widely used tool to understand the behaviour of complex systems in the last decade. We start from a short description of structural rigidity theory. A detailed account on the combinatorial rigidity analysis of protein structures, as well as local flexibility measures of proteins and their applications in explaining allostery and thermostability is given. We also briefly discuss the network aspects of cytoskeletal tensegrity. Finally, we show the importance of the balance between functional flexibility and rigidity in protein-protein interaction, metabolic, gene regulatory and neuronal networks. Our summary raises the possibility that the concepts of flexibility and rigidity can be generalized to all networks. PMID:23165349

  13. Flexible Personnel Scheduling in the Parallel Environment

    Institute of Scientific and Technical Information of China (English)

    XU Ben-zhu; ZHANG Xing-ling

    2014-01-01

    In the view of staff shortages and the huge inventory of products in the current market, we put forward a personnel scheduling model in the target of closing to the delivery date considering the parallelism. Then we designed a scheduling algorithm based on genetic algorithm and proposed a flexible parallel decoding method which take full use of the personal capacity. Case study results indicate that the flexible personnel scheduling considering the order-shop scheduling, machine automatic capabilities and personnel flexible in the target of closing to the delivery date optimize the allocation of human resources, then maximize the efficiency.

  14. Flexible structured high-frequency film bulk acoustic resonator for flexible wireless electronics

    International Nuclear Information System (INIS)

    Flexible electronics have inspired many novel and very important applications in recent years and various flexible electronic devices such as diodes, transistors, circuits, sensors, and radiofrequency (RF) passive devices including antennas and inductors have been reported. However, the lack of a high-performance RF resonator is one of the key bottlenecks to implement flexible wireless electronics. In this study, for the first time, a novel ultra-flexible structured film bulk acoustic resonator (FBAR) is proposed. The flexible FBAR is fabricated on a flexible polyimide substrate using piezoelectric thin film aluminum nitride (AlN) for acoustic wave excitation. Both the shear wave and longitudinal wave can be excited under the surface interdigital electrodes configuration we proposed. In the case of the thickness extension mode, a flexible resonator with a working frequency as high as of 5.2325 GHz has been realized. The resonators stay fully functional under bending status and after repeated bending and re-flattening operations. This flexible high-frequency resonator will serve as a key building block for the future flexible wireless electronics, greatly expanding the application scope of flexible electronics. (paper)

  15. Electrostatics and Intrinsic Disorder Drive Translocon Binding of the SRP Receptor FtsY.

    Science.gov (United States)

    Lakomek, Nils-Alexander; Draycheva, Albena; Bornemann, Thomas; Wintermeyer, Wolfgang

    2016-08-01

    Integral membrane proteins in bacteria are co-translationally targeted to the SecYEG translocon for membrane insertion via the signal recognition particle (SRP) pathway. The SRP receptor FtsY and its N-terminal A domain, which is lacking in any structural model of FtsY, were studied using NMR and fluorescence spectroscopy. The A domain is mainly disordered and highly flexible; it binds to lipids via its N terminus and the C-terminal membrane targeting sequence. The central A domain binds to the translocon non-specifically and maintains disorder. Translocon targeting and binding of the A domain is driven by electrostatic interactions. The intrinsically disordered A domain tethers FtsY to the translocon, and because of its flexibility, allows the FtsY NG domain to scan a large area for binding to the NG domain of ribosome-bound SRP, thereby promoting the formation of the quaternary transfer complex at the membrane. PMID:27346853

  16. Conserved high-affinity NF-kappa B binding site in the interferon regulatory factor-1 promoter is not occupied by NF-kappa B in vivo and is transcriptionally inactive.

    Science.gov (United States)

    Rein, T; Schreck, R; Willenbrink, W; Neubert, W J; Zorbas, H; Bäuerle, P A

    1995-01-01

    The promoter of the interferon regulatory factor-1 (IRF-1) gene contains at position -47 to -38 an evolutionary conserved binding sequence for the inducible transcription factor NF-kappa B. This site is highly homologous to a transcriptionally active site from the MHC class I enhancer. In this study, we show by in vitro assays using purified NF-kappa B that the kappa B motif in the IRF-1 promoter binds the factor specifically and with high affinity, comparable to various other cis-acting kappa B elements. Two copies of the IRF-1 kappa B site fused to the heterologous c-fos promoter conferred induction of a chloramphenicol acetyl transferase (CAT) reported gene in response to stimulation of L929 fibroblasts with various NF-kappa B inducers, such as tumor necrosis factor alpha (TNF alpha) or phorbol 12-myristate 13-acetate (PMA). Mutation of the binding site completely abolished transcriptional inducibility of the heterologous promoter. Surprisingly, the same IRF-1 kappa B motif in context of the homologous IRF-1 promoter was transcriptionally inactive in CAT assays. The very weak induction of the IRF-1 promoter in response to TNF treatment or infection of fibroblasts with Newcastle disease virus (NDV) was barely affected by point mutation of the kappa B site or loss of the site by truncation of the promoter. Analysis of the occupational state of the chromosomal IRF-1 kappa B site by in vivo foot-printing revealed that no footprint was induced over the kappa B motif in the IRF-1 promoter after PMA treatment of L929 fibroblast cells, despite the simultaneous induction of IRF-1 mRNA and NF-kappa B binding activity. Constitutive footprints were detected at a CCAAT and GC-rich region in the promoter. This is the first example of a high-affinity NF-kappa B binding site within a promoter which may not participate in transcriptional regulation under conditions activating NF-kappa B DNA binding and gene expression. PMID:8867671

  17. Strain Monitoring of Flexible Structures

    Science.gov (United States)

    Litteken, Douglas A.

    2017-01-01

    One of the biggest challenges facing NASA's deep space exploration goals is structural mass. A long duration transit vehicle on a journey to Mars, for example, requires a large internal volume for cargo, supplies and crew support. As with all space structures, a large pressure vessel is not enough. The vehicle also requires thermal, micro-meteoroid, and radiation protection, a navigation and control system, a propulsion system, and a power system, etc. As vehicles get larger, their associated systems also get larger and more complex. These vehicles require larger lift capacities and force the mission to become extremely costly. In order to build large volume habitable vehicles, with only minimal increases in launch volume and mass, NASA is developing lightweight structures. Lightweight structures are made from non-metallic materials including graphite composites and high strength fabrics and could provide similar or better structural capability than metals, but with significant launch volume and mass savings. Fabric structures specifically, have been worked by NASA off and on since its inception, but most notably in the 1990's with the TransHAB program. These TransHAB developed structures use a layered material approach to form a pressure vessel with integrated thermal and micro-meteoroid and orbital debris (MMOD) protection. The flexible fabrics allow the vessel to be packed in a small volume during launch and expand into a much larger volume once in orbit. NASA and Bigelow Aerospace recently installed the first human-rated inflatable module on the International Space Station (ISS), known as the Bigelow Expandable Activity Module (BEAM) in May of 2016. The module provides a similar internal volume to that of an Orbital ATK Cygnus cargo vehicle, but with a 77% launch volume savings. As lightweight structures are developed, testing methods are vital to understanding their behavior and validating analytical models. Common techniques can be applied to fabric materials

  18. Statistical analysis of structural determinants for protein-DNA-binding specificity.

    Science.gov (United States)

    Corona, Rosario I; Guo, Jun-Tao

    2016-08-01

    DNA-binding proteins play critical roles in biological processes including gene expression, DNA packaging and DNA repair. They bind to DNA target sequences with different degrees of binding specificity, ranging from highly specific (HS) to nonspecific (NS). Alterations of DNA-binding specificity, due to either genetic variation or somatic mutations, can lead to various diseases. In this study, a comparative analysis of protein-DNA complex structures was carried out to investigate the structural features that contribute to binding specificity. Protein-DNA complexes were grouped into three general classes based on degrees of binding specificity: HS, multispecific (MS), and NS. Our results show a clear trend of structural features among the three classes, including amino acid binding propensities, simple and complex hydrogen bonds, major/minor groove and base contacts, and DNA shape. We found that aspartate is enriched in HS DNA binding proteins and predominately binds to a cytosine through a single hydrogen bond or two consecutive cytosines through bidentate hydrogen bonds. Aromatic residues, histidine and tyrosine, are highly enriched in the HS and MS groups and may contribute to specific binding through different mechanisms. To further investigate the role of protein flexibility in specific protein-DNA recognition, we analyzed the conformational changes between the bound and unbound states of DNA-binding proteins and structural variations. The results indicate that HS and MS DNA-binding domains have larger conformational changes upon DNA-binding and larger degree of flexibility in both bound and unbound states. Proteins 2016; 84:1147-1161. © 2016 Wiley Periodicals, Inc.

  19. Multisensory integration : flexible use of general operations

    NARCIS (Netherlands)

    Van Atteveldt, N.; Murray, Micah M; Thut, Gregor; Schroeder, Charles E

    2014-01-01

    Research into the anatomical substrates and "principles" for integrating inputs from separate sensory surfaces has yielded divergent findings. This suggests that multisensory integration is flexible and context dependent and underlines the need for dynamically adaptive neuronal integration mechanism

  20. Sources of Operational Flexibility, Greening the Grid

    Energy Technology Data Exchange (ETDEWEB)

    Katz, Jessica; Milligan, Michael; Cochran, Jaquelin

    2015-05-01

    Changes in electricity demand and generation must be constantly balanced to maintain power system stability and reliability. Operational flexibility refers to the ability of a power system to respond to these changes. Power systems are designed and operated to efficiently manage variability and uncertainty in electricity demand and resource availability. Variable renewable energy (VRE) increases this inherent variability and uncertainty, and thus increases the need for flexibility. Systems with significant variability and uncertainty require flexible generators that can rapidly change output, operate efficiently at lower outputs, and operate for short durations. This flexibility in turn can reduce the need to curtail (decrease the output of) solar and wind generation; improve investor confidence in VRE and revenue streams; decrease the risk of negative market pricing (which results when conventional generators cannot turn down to low outputs during times of high VRE output); and reduce environmental impacts by increasing system efficiency and maximizing the utilization of VRE.

  1. Graphene-Based Flexible and Stretchable Electronics.

    Science.gov (United States)

    Jang, Houk; Park, Yong Ju; Chen, Xiang; Das, Tanmoy; Kim, Min-Seok; Ahn, Jong-Hyun

    2016-06-01

    Graphene provides outstanding properties that can be integrated into various flexible and stretchable electronic devices in a conventional, scalable fashion. The mechanical, electrical, and optical properties of graphene make it an attractive candidate for applications in electronics, energy-harvesting devices, sensors, and other systems. Recent research progress on graphene-based flexible and stretchable electronics is reviewed here. The production and fabrication methods used for target device applications are first briefly discussed. Then, the various types of flexible and stretchable electronic devices that are enabled by graphene are discussed, including logic devices, energy-harvesting devices, sensors, and bioinspired devices. The results represent important steps in the development of graphene-based electronics that could find applications in the area of flexible and stretchable electronics.

  2. Carbon Nanotube Flexible and Stretchable Electronics.

    Science.gov (United States)

    Cai, Le; Wang, Chuan

    2015-12-01

    The low-cost and large-area manufacturing of flexible and stretchable electronics using printing processes could radically change people's perspectives on electronics and substantially expand the spectrum of potential applications. Examples range from personalized wearable electronics to large-area smart wallpapers and from interactive bio-inspired robots to implantable health/medical apparatus. Owing to its one-dimensional structure and superior electrical property, carbon nanotube is one of the most promising material platforms for flexible and stretchable electronics. Here in this paper, we review the recent progress in this field. Applications of single-wall carbon nanotube networks as channel semiconductor in flexible thin-film transistors and integrated circuits, as stretchable conductors in various sensors, and as channel material in stretchable transistors will be discussed. Lastly, state-of-the-art advancement on printing process, which is ideal for large-scale fabrication of flexible and stretchable electronics, will also be reviewed in detail.

  3. On semiflexible, flexible and pie algebras

    CERN Document Server

    Bourke, John

    2011-01-01

    We introduce the notion of pie algebra for a 2-monad, these bearing the same relationship to the flexible and semiflexible algebras as pie limits do to flexible and semiflexible ones. We see that in many cases, the pie algebras are precisely those "free at the level of objects" in a suitable sense; so that, for instance, a strict monoidal category is pie just when its underlying monoid of objects is free. Pie algebras are contrasted with flexible and semiflexible algebras via a series of characterisations of each class; particular attention is paid to the case of pie, flexible and semiflexible weights, these being characterised in terms of the behaviour of the corresponding weighted limit functors.

  4. Piezoelectric RL shunt damping of flexible structures

    DEFF Research Database (Denmark)

    Høgsberg, Jan Becker; Krenk, Steen

    2015-01-01

    Resonant RL shunt circuits represent a robust and effective approach to piezoelectric damping, provided that the individual shunt circuit components are calibrated accurately with respect to the dynamic properties of the corresponding flexible structure. The balanced calibration procedure applied...

  5. Flexible Hall sensors based on graphene

    Science.gov (United States)

    Wang, Zhenxing; Shaygan, Mehrdad; Otto, Martin; Schall, Daniel; Neumaier, Daniel

    2016-03-01

    The excellent electronic and mechanical properties of graphene provide a perfect basis for high performance flexible electronic and sensor devices. Here, we present the fabrication and characterization of flexible graphene based Hall sensors. The Hall sensors are fabricated on 50 μm thick flexible Kapton foil using large scale graphene grown by chemical vapor deposition technique on copper foil. Voltage and current normalized sensitivities of up to 0.096 V VT-1 and 79 V AT-1 were measured, respectively. These values are comparable to the sensitivity of rigid silicon based Hall sensors and are the highest values reported so far for any flexible Hall sensor devices. The sensitivity of the Hall sensor shows no degradation after being bent to a minimum radius of 4 mm, which corresponds to a tensile strain of 0.6%, and after 1000 bending cycles to a radius of 5 mm.

  6. Flexible HVAC System for Lab or Classroom.

    Science.gov (United States)

    Friedan, Jonathan

    2001-01-01

    Discusses an effort to design a heating, ventilation, and air conditioning system flexible enough to accommodate an easy conversion of classrooms to laboratories and dry labs to wet labs. The design's energy efficiency and operations and maintenance are examined. (GR)

  7. Carbon Nanotube Flexible and Stretchable Electronics

    Science.gov (United States)

    Cai, Le; Wang, Chuan

    2015-08-01

    The low-cost and large-area manufacturing of flexible and stretchable electronics using printing processes could radically change people's perspectives on electronics and substantially expand the spectrum of potential applications. Examples range from personalized wearable electronics to large-area smart wallpapers and from interactive bio-inspired robots to implantable health/medical apparatus. Owing to its one-dimensional structure and superior electrical property, carbon nanotube is one of the most promising material platforms for flexible and stretchable electronics. Here in this paper, we review the recent progress in this field. Applications of single-wall carbon nanotube networks as channel semiconductor in flexible thin-film transistors and integrated circuits, as stretchable conductors in various sensors, and as channel material in stretchable transistors will be discussed. Lastly, state-of-the-art advancement on printing process, which is ideal for large-scale fabrication of flexible and stretchable electronics, will also be reviewed in detail.

  8. Thin Flexible IMM Solar Array Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Inverted Metamorphic (IMM) solar cells have achieved high efficiency at very low mass, but integration of the thin crystalline photovoltaic device into a flexible...

  9. Fully Integral, Flexible Composite Driveshaft Project

    Data.gov (United States)

    National Aeronautics and Space Administration — An all-composite driveshaft incorporating integral flexible diaphragms is described and proposed for phase II prime conractor testing. The approach obsoletes the...

  10. Fully Integral, Flexible Composite Driveshaft Project

    Data.gov (United States)

    National Aeronautics and Space Administration — An all-composite driveshaft incorporating integral flexible diaphragms is described and proposed for further refinement. An approach is explored which obsoletes the...

  11. Thin Flexible IMM Solar Array Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Thin, flexible, and highly efficient solar arrays are needed that package compactly for launch and deploy into large, structurally stable high power generators....

  12. Binding-site assessment by virtual fragment screening.

    Directory of Open Access Journals (Sweden)

    Niu Huang

    Full Text Available The accurate prediction of protein druggability (propensity to bind high-affinity drug-like small molecules would greatly benefit the fields of chemical genomics and drug discovery. We have developed a novel approach to quantitatively assess protein druggability by computationally screening a fragment-like compound library. In analogy to NMR-based fragment screening, we dock approximately 11,000 fragments against a given binding site and compute a computational hit rate based on the fraction of molecules that exceed an empirically chosen score cutoff. We perform a large-scale evaluation of the approach on four datasets, totaling 152 binding sites. We demonstrate that computed hit rates correlate with hit rates measured experimentally in a previously published NMR-based screening method. Secondly, we show that the in silico fragment screening method can be used to distinguish known druggable and non-druggable targets, including both enzymes and protein-protein interaction sites. Finally, we explore the sensitivity of the results to different receptor conformations, including flexible protein-protein interaction sites. Besides its original aim to assess druggability of different protein targets, this method could be used to identifying druggable conformations of flexible binding site for lead discovery, and suggesting strategies for growing or joining initial fragment hits to obtain more potent inhibitors.

  13. Flexibility decline contributes to similarity of past and future thinking in Alzheimer's disease.

    Science.gov (United States)

    El Haj, Mohamad; Antoine, Pascal; Kapogiannis, Dimitrios

    2015-11-01

    A striking similarity has been suggested between past and future thinking in Alzheimer's Disease (AD), a similarity attributable to abnormalities in common modular cognitive functions and neuroanatomical substrates. This study extends this literature by identifying specific executive function deficits underlying past and future thinking in AD. Twenty-four participants with a clinical diagnosis of probable (mild) AD and 26 older controls generated past and future events and underwent tests of binding and the executive functions of flexibility, inhibition, and updating. AD patients showed similar autobiographical performances in past and future event generation, and so did control participants. In each group, the similarity of past and future thinking was predicted by flexibility. Furthermore, AD patients with low flexibility showed higher similarity of past and future thinking than those with high flexibility. These findings are interpreted in terms of involvement of the hippocampus and frontal lobes in future thinking. Deficits in these brain regions in AD are likely to compromise the ability to recombine episodic information into novel and flexible configurations as scenarios for the future.

  14. Skills and Recruitment in Flexible Work Settings

    OpenAIRE

    Apitzsch, Birgit

    2012-01-01

    Over recent decades, we have witnessed profound changes in labour markets with an increase in flexible forms of work and employment, driven by organizational restructuring and institutional change at the macro- and at the sectoral level. In order to understand transformations of employment it is central to grasp the interrelations between the organisation of work, recruitment practices, and labour market institutions. Yet, despite the growing interest in flexible work practices and the growin...

  15. Consumption Flexibility, Product Configuration, and Market Competition

    OpenAIRE

    Liang Guo

    2006-01-01

    When purchase and consumption decisions are separated in time and when future utility is state dependent, consumers may desire to pursue consumption flexibility by purchasing different products together (multiple buying). This paper analyzes the effects of consumption flexibility on competing firms' marketing mix decisions, in a model in which future preference uncertainty exists and consumers differ in their preferred product location on a horizontal attribute. The analysis shows that the na...

  16. External Job Churning and Internal Job Flexibility

    OpenAIRE

    Peter Cappelli; David Neumark

    2001-01-01

    Concern about job instability and insecurity has a long history and has generated a considerable body of research across the social sciences, most recently focused on whether job stability and security have declined. Internally flexible systems for organizing work, sometimes called 'functionally flexible' systems, have been proposed as arrangements that can reduce job instability and insecurity by reducing the need for firms to rely on job cuts or contingent work to be able to respond to chan...

  17. Flexible thin-film planar peltier microcooler

    OpenAIRE

    L.M. Gonçalves; Couto, Carlos; Correia, J.H.; Alpuim, P.; Min, Gao; Rowe, D. M.

    2006-01-01

    The present work reports on the fabrication and characterization of the first planar Peltier microcooler on a flexible substrate. The microcooler was fabricated on flexible Kapton© polyimide substrate, 25 μm in thickness, using Bi2Te3 and Sb2Te3 thermoelectric elements, and was deposited by thermal co-evaporation. Portuguese Foundation for Science and Technology (SFRH/BD/18142/2004) Agência de Inovação (POCTI MPYROM)

  18. Access to flexible working and informal care

    OpenAIRE

    Bryan, Mark L.

    2011-01-01

    We use matched employer-employee data to explore the relationship between employees' access to flexible working arrangements and the amount of informal care they provide to sick or elderly friends and relatives. Flexitime and the ability to reduce working hours are each associated with about 10% more hours of informal care, with effects concentrated among full-time workers providing small amounts of care. The wider workplace environment beyond formal flexible work also appears to facilitate c...

  19. Correlated Flexible Molecular Coding and Molecular Evolvability

    OpenAIRE

    Husimi, Y; Aita, T.; Tabuchi, I.

    2002-01-01

    Evolvability of biopolymers is based on molecular coding. The molecular coding is represented by biopolymer function vs monomeric sequence relationship, that is, a proper fitness landscape on the sequence space. On the other hand, molecular coding is mostly realized by monomeric sequence vs biopolymer structure relationship. We suggest the evolution of evolvability based on flexible or multiplex coding originating from flexible or polymorphic conformation of evolving biopolymers. We report a ...

  20. Composite materials in flexible multibody systems

    OpenAIRE

    Neto, Maria Augusta; Ambrósio, Jorge A. C.; Leal, Rogério P.

    2006-01-01

    In this work the flexible multibody dynamics formulations of complex models are extended to include elastic components made of laminated composite materials. The only limitation for the deformation of a structural member is that it must be elastic and linear when described in a body fixed frame. A finite element model for each flexible body is obtained such that the nodal coordinates are described with respect to the body fixed frame and the inertia terms involved in the mass matrix and gyros...

  1. Spacecraft Dynamic Characteristics While Deploying Flexible Beams

    Institute of Scientific and Technical Information of China (English)

    程绪铎; 李俊峰; 樊勇; 王照林

    2002-01-01

    The attitude dynamic equations of a spacecraft while deploying two flexible beams and the beam equations were developed from momentum theory. The dynamic equations were solved numerically using the Runge-Kutta method to calculate the vibration amplitudes of the flexible beams and the attitude angular velocity. The results show that the vibration amplitudes increase as the beam length increases or as the initial attitude angular velocity increases. The results also show that the vibration amplitudes decrease as the deployment velocity increases.

  2. Technical Design of Flexible Sustainable Energy Systems

    DEFF Research Database (Denmark)

    Lund, Henrik

    2003-01-01

    The paper presents technical designs of potential future flexible energy systems in Denmark, which will be able both to balance production and demand and to secure voltage and frequency requirements on the grid.......The paper presents technical designs of potential future flexible energy systems in Denmark, which will be able both to balance production and demand and to secure voltage and frequency requirements on the grid....

  3. Stochastic Dynamics Underlying Cognitive Stability and Flexibility

    OpenAIRE

    Kai Ueltzhöffer; Armbruster-Genç, Diana J. N.; Christian J Fiebach

    2015-01-01

    Cognitive stability and flexibility are core functions in the successful pursuit of behavioral goals. While there is evidence for a common frontoparietal network underlying both functions and for a key role of dopamine in the modulation of flexible versus stable behavior, the exact neurocomputational mechanisms underlying those executive functions and their adaptation to environmental demands are still unclear. In this work we study the neurocomputational mechanisms underlying cue based task ...

  4. Flexible Employment Arrangements and Workplace Performance

    OpenAIRE

    Giovanis, Eleftherios

    2016-01-01

    There is an increasing concern on the quality of jobs and productivity that is witnessed in the flexible employment arrangements. However, the effects of the employment flexible types on workplace performance has not been explored in Britain. In this study the relationship between two employment arrangements and the workplace performance is examined. More specifically, teleworking and compress hours are two main employment types examined using the Workplace Employee R...

  5. Fast Flexible Transistors with a Nanotrench Structure

    OpenAIRE

    Jung-Hun Seo; Tao Ling; Shaoqin Gong; Weidong Zhou; Alice L. Ma; L. Jay Guo; Zhenqiang Ma

    2016-01-01

    The simplification of fabrication processes that can define very fine patterns for large-area flexible radio-frequency (RF) applications is very desirable because it is generally very challenging to realize submicron scale patterns on flexible substrates. Conventional nanoscale patterning methods, such as e-beam lithography, cannot be easily applied to such applications. On the other hand, recent advances in nanoimprinting lithography (NIL) may enable the fabrication of large-area nanoelectro...

  6. A Flexible Nurse Scheduling Support System

    OpenAIRE

    Ozkarahan, Irem

    1987-01-01

    Scheduling nursing personnel in hospitals is very complex because of the variety of conflicting interests and objectives. Also, demand varies 24-hour a day 7-day a week, is skill specific and hard to forecast. In the face of this complexity, the present nurse scheduling models have met with little success. In this paper, we propose a more flexible decision support system that will satisfy the interests of both hospitals and nurses through alternative models that attempt to accommodate flexibl...

  7. Entry and exit decisions in flexible teams

    OpenAIRE

    Michael Christensen; Thorbjørn Knudsen

    2008-01-01

    The present study identifies a major limitation of current research on multinational enterprises (MNEs). Joint decision-making in a distributed setting is of critical importance in practice, but has received little attention in our theories. To address this gap in knowledge, we examine the effects of flexible decision teams when MNEs assess turbulent markets. Remarkably, flexible teams composed of fallible evaluators can outperform what is usually thought of as an “optimal” decision. Our main...

  8. Spatial operator algebra for flexible multibody dynamics

    Science.gov (United States)

    Jain, A.; Rodriguez, G.

    1993-01-01

    This paper presents an approach to modeling the dynamics of flexible multibody systems such as flexible spacecraft and limber space robotic systems. A large number of degrees of freedom and complex dynamic interactions are typical in these systems. This paper uses spatial operators to develop efficient recursive algorithms for the dynamics of these systems. This approach very efficiently manages complexity by means of a hierarchy of mathematical operations.

  9. Flexibility in natural gas supply and demand

    OpenAIRE

    Cornot-Gandolphe, Sylvie

    2015-01-01

    "In most IEA Member countries, natural gas demand varies strongly during the year, according to temperature. Flexibility is needed to cover seasonal swings and variations in gas demand, especially for household customers. It is also needed to maintain short-term supply security in the case of a disruption of a supply source. Over the years, gas companies have devised a variety of flexibility tools, such as supply swing, storage and interruptible contracts. This enabled them to balance supply ...

  10. Biaxially oriented film on flexible polymeric substrate

    Science.gov (United States)

    Finkikoglu, Alp T.; Matias, Vladimir

    2009-10-13

    A flexible polymer-based template having a biaxially oriented film grown on the surface of a polymeric substrate. The template having the biaxially oriented film can be used for further epitaxial growth of films of interest for applications such as photovoltaic cells, light emitting diodes, and the like. Methods of forming such a flexible template and providing the polymeric substrate with a biaxially oriented film deposited thereon are also described.

  11. Instant Attraction: Immediate Action-Effect Bindings Occur for Both, Stimulus- and Goal-Driven Actions

    OpenAIRE

    Janczyk, Markus; Heinemann, Alexander; Pfister, Roland

    2012-01-01

    Flexible behavior is only possible if contingencies between own actions and following environmental effects are acquired as quickly as possible; and recent findings indeed point toward an immediate formation of action-effect bindings already after a single coupling of an action and its effect. The present study explored whether these short-term bindings occur for both, stimulus- and goal-driven actions (“forced-choice actions” vs. “free-choice actions”). Two experiments confirmed that immedia...

  12. Flexible ERP: Enterprise Information System Under the Agile Manufacture Mode

    Institute of Scientific and Technical Information of China (English)

    SU Xuanliang; CHENG Guoping; WANG Mingquan

    2006-01-01

    Flexibility is the demand of management revolution, and also the milestone of management development. The flexible ERP system is the information system to orientate variety and handle uncertainties. The market with rapid change and agile manufacture need a flexible ERP system.The article elaborates the meanings and characteristics about flexibility, the flexibility of ERP and the flexible ERP system; it discussed the necessity, the possibility and the related condition of setting up the flexible ERP system; and puts forward the strategy and the approaches of setting up the flexible ERP system.

  13. Enabling Technologies for Fabrication of Large Area Flexible Antennas Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Flexible, foldable, and/or inflatable antenna systems open up a wealth of opportunities. Integrating antenna elements and related electronics onto flexible...

  14. Flexible Thermoelectric Generators on Silicon Fabric

    KAUST Repository

    Sevilla, Galo T.

    2012-11-01

    In this work, the development of a Thermoelectric Generator on Flexible Silicon Fabric is explored to extend silicon electronics for flexible platforms. Low cost, easily deployable plastic based flexible electronics are of great interest for smart textile, wearable electronics and many other exciting applications. However, low thermal budget processing and fundamentally limited electron mobility hinders its potential to be competitive with well established and highly developed silicon technology. The use of silicon in flexible electronics involve expensive and abrasive materials and processes. In this work, high performance flexible thermoelectric energy harvesters are demonstrated from low cost bulk silicon (100) wafers. The fabrication of the micro- harvesters was done using existing silicon processes on silicon (100) and then peeled them off from the original substrate leaving it for reuse. Peeled off silicon has 3.6% thickness of bulk silicon reducing the thermal loss significantly and generating nearly 30% more output power than unpeeled harvesters. The demonstrated generic batch processing shows a pragmatic way of peeling off a whole silicon circuitry after conventional fabrication on bulk silicon wafers for extremely deformable high performance integrated electronics. In summary, by using a novel, low cost process, this work has successfully integrated existing and highly developed fabrication techniques to introduce a flexible energy harvester for sustainable applications.

  15. Fast Flexible Transistors with a Nanotrench Structure

    Science.gov (United States)

    Seo, Jung-Hun; Ling, Tao; Gong, Shaoqin; Zhou, Weidong; Ma, Alice L.; Guo, L. Jay; Ma, Zhenqiang

    2016-04-01

    The simplification of fabrication processes that can define very fine patterns for large-area flexible radio-frequency (RF) applications is very desirable because it is generally very challenging to realize submicron scale patterns on flexible substrates. Conventional nanoscale patterning methods, such as e-beam lithography, cannot be easily applied to such applications. On the other hand, recent advances in nanoimprinting lithography (NIL) may enable the fabrication of large-area nanoelectronics, especially flexible RF electronics with finely defined patterns, thereby significantly broadening RF applications. Here we report a generic strategy for fabricating high-performance flexible Si nanomembrane (NM)-based RF thin-film transistors (TFTs), capable of over 100 GHz operation in theory, with NIL patterned deep-submicron-scale channel lengths. A unique 3-dimensional etched-trench-channel configuration was used to allow for TFT fabrication compatible with flexible substrates. Optimal device parameters were obtained through device simulation to understand the underlying device physics and to enhance device controllability. Experimentally, a record-breaking 38 GHz maximum oscillation frequency fmax value has been successfully demonstrated from TFTs with a 2 μm gate length built with flexible Si NM on plastic substrates.

  16. Fast Flexible Transistors with a Nanotrench Structure.

    Science.gov (United States)

    Seo, Jung-Hun; Ling, Tao; Gong, Shaoqin; Zhou, Weidong; Ma, Alice L; Guo, L Jay; Ma, Zhenqiang

    2016-04-20

    The simplification of fabrication processes that can define very fine patterns for large-area flexible radio-frequency (RF) applications is very desirable because it is generally very challenging to realize submicron scale patterns on flexible substrates. Conventional nanoscale patterning methods, such as e-beam lithography, cannot be easily applied to such applications. On the other hand, recent advances in nanoimprinting lithography (NIL) may enable the fabrication of large-area nanoelectronics, especially flexible RF electronics with finely defined patterns, thereby significantly broadening RF applications. Here we report a generic strategy for fabricating high-performance flexible Si nanomembrane (NM)-based RF thin-film transistors (TFTs), capable of over 100 GHz operation in theory, with NIL patterned deep-submicron-scale channel lengths. A unique 3-dimensional etched-trench-channel configuration was used to allow for TFT fabrication compatible with flexible substrates. Optimal device parameters were obtained through device simulation to understand the underlying device physics and to enhance device controllability. Experimentally, a record-breaking 38 GHz maximum oscillation frequency fmax value has been successfully demonstrated from TFTs with a 2 μm gate length built with flexible Si NM on plastic substrates.

  17. Multibody Dynamics of Very Flexible Damped Systems

    International Nuclear Information System (INIS)

    An efficient multibody dynamics formulation is presented for simulating the forward dynamics of open and closed loop mechanical systems comprised of rigid and flexible bodies interconnected by revolute, prismatic, free, and fixed joints. Geometrically nonlinear deformation of flexible bodies is included and the formulation does not impose restrictions on the representation of material damping within flexible bodies. The approach is based on Kane's equation without multipliers and the resulting formulation generates 2ndof+m first order ordinary differential equations directly where 2nd of is the smallest number of system degrees of freedom that can completely describe the system configuration and m is the number of loop closure velocity constraint equations. The equations are integrated numerically in the time domain to propagate the solution. Flexible bodies are discretized using a finite element approach. The mass and stiffness matrices for a six-degree-of-freedom planar beam element are developed including mass coupling terms, rotary inertia, centripetal and Coriolis forces, and geometric stiffening terms. The formulation is implemented in the general purpose multibody dynamics computer program 'flxdyn'. Extensive validation of the formulation and corresponding computer program is accomplished by comparing results with analytically derived equations, alternative approximate solutions, and benchmark problems selected from the literature. The formulation is found to perform well in terms of accuracy and solution efficiency. This article develops the formulation and presents a set of validation problems including a sliding pendulum, seven link mechanism, flexible beam spin-up problem, and flexible slider crank mechanism

  18. Fast Flexible Transistors with a Nanotrench Structure.

    Science.gov (United States)

    Seo, Jung-Hun; Ling, Tao; Gong, Shaoqin; Zhou, Weidong; Ma, Alice L; Guo, L Jay; Ma, Zhenqiang

    2016-01-01

    The simplification of fabrication processes that can define very fine patterns for large-area flexible radio-frequency (RF) applications is very desirable because it is generally very challenging to realize submicron scale patterns on flexible substrates. Conventional nanoscale patterning methods, such as e-beam lithography, cannot be easily applied to such applications. On the other hand, recent advances in nanoimprinting lithography (NIL) may enable the fabrication of large-area nanoelectronics, especially flexible RF electronics with finely defined patterns, thereby significantly broadening RF applications. Here we report a generic strategy for fabricating high-performance flexible Si nanomembrane (NM)-based RF thin-film transistors (TFTs), capable of over 100 GHz operation in theory, with NIL patterned deep-submicron-scale channel lengths. A unique 3-dimensional etched-trench-channel configuration was used to allow for TFT fabrication compatible with flexible substrates. Optimal device parameters were obtained through device simulation to understand the underlying device physics and to enhance device controllability. Experimentally, a record-breaking 38 GHz maximum oscillation frequency fmax value has been successfully demonstrated from TFTs with a 2 μm gate length built with flexible Si NM on plastic substrates. PMID:27094686

  19. Multibody Dynamics of Very Flexible Damped Systems

    Energy Technology Data Exchange (ETDEWEB)

    Langlois, R.G.; Anderson, R.J. [Queen' s University at Kingston, Department of Mechanical Engineering (Canada)

    1999-05-15

    An efficient multibody dynamics formulation is presented for simulating the forward dynamics of open and closed loop mechanical systems comprised of rigid and flexible bodies interconnected by revolute, prismatic, free, and fixed joints. Geometrically nonlinear deformation of flexible bodies is included and the formulation does not impose restrictions on the representation of material damping within flexible bodies. The approach is based on Kane's equation without multipliers and the resulting formulation generates 2ndof+m first order ordinary differential equations directly where 2nd of is the smallest number of system degrees of freedom that can completely describe the system configuration and m is the number of loop closure velocity constraint equations. The equations are integrated numerically in the time domain to propagate the solution. Flexible bodies are discretized using a finite element approach. The mass and stiffness matrices for a six-degree-of-freedom planar beam element are developed including mass coupling terms, rotary inertia, centripetal and Coriolis forces, and geometric stiffening terms. The formulation is implemented in the general purpose multibody dynamics computer program 'flxdyn'. Extensive validation of the formulation and corresponding computer program is accomplished by comparing results with analytically derived equations, alternative approximate solutions, and benchmark problems selected from the literature. The formulation is found to perform well in terms of accuracy and solution efficiency. This article develops the formulation and presents a set of validation problems including a sliding pendulum, seven link mechanism, flexible beam spin-up problem, and flexible slider crank mechanism.

  20. Flexible conductive nanocellulose combined with silicon nanoparticles and polyaniline.

    Science.gov (United States)

    Park, Minsung; Lee, Dajung; Shin, Sungchul; Kim, Hyun-Joong; Hyun, Jinho

    2016-04-20

    Here we describe a unique conductive bacterial cellulose (BC) composite with silicon nanoparticles (SiNPs) and polyaniline. BC was used as a template for binding SiNPs resulting in a very promising anode material for Li-ion rechargeable batteries that showed a high specific capacity. The surfaces of the SiNPs were modified with phytic acid to enhance the binding of aniline monomer to the surface. A conformal coating of polyaniline (PANi) was formed on the modified SiNPs by in situ polymerization of aniline monomers. We also found that the phytic acid on the SiNPs was critical to ensure encapsulation of SiNPs with PANi. In addition, the phosphoric acid-tagged surface of the SiNPs enhanced the adhesion of SiNPs to the BC fibers. The resulting three dimensional network of BC was flexible and provided stress dissipation in the conductive BC composites. Flexural testing of conductive BC composites showed stable electrical conductivity even after repetitive bending over 100 times. PMID:26876826

  1. Ligand Binding Thermodynamics in Drug Discovery: Still a Hot Tip?

    Science.gov (United States)

    Geschwindner, Stefan; Ulander, Johan; Johansson, Patrik

    2015-08-27

    The use of ligand binding thermodynamics has been proposed as a potential success factor to accelerate drug discovery. However, despite the intuitive appeal of optimizing binding enthalpy, a number of factors complicate routine use of thermodynamic data. On a macroscopic level, a range of experimental parameters including temperature and buffer choice significantly influence the observed thermodynamic signatures. On a microscopic level, solute effects, structural flexibility, and cooperativity lead to nonlinear changes in enthalpy. This multifactorial character hides essential enthalpy contributions of intermolecular contacts, making them experimentally nonobservable. In this perspective, we present three case studies, reflect on some key factors affecting thermodynamic signatures, and investigate their relation to the hydrophobic effect, enthalpy-entropy compensation, lipophilic ligand efficiency, and promiscuity. The studies highlight that enthalpy and entropy cannot be used as direct end points but can together with calculations increase our understanding of ligand binding and identify interesting outliers that do not behave as expected.

  2. Competitive Binding of Natural Amphiphiles with Graphene Derivatives

    Science.gov (United States)

    Radic, Slaven; Geitner, Nicholas K.; Podila, Ramakrishna; Käkinen, Aleksandr; Chen, Pengyu; Ke, Pu Chun; Ding, Feng

    2013-07-01

    Understanding the transformation of graphene derivatives by natural amphiphiles is essential for elucidating the biological and environmental implications of this emerging class of engineered nanomaterials. Using rapid discrete-molecular-dynamics simulations, we examined the binding of graphene and graphene oxide with peptides, fatty acids, and cellulose, and complemented our simulations by experimental studies of Raman spectroscopy, FTIR, and UV-Vis spectrophotometry. Specifically, we established a connection between the differential binding and the conformational flexibility, molecular geometry, and hydrocarbon content of the amphiphiles. Importantly, our dynamics simulations revealed a Vroman-like competitive binding of the amphiphiles for the graphene oxide substrate. This study provides a mechanistic basis for addressing the transformation, evolution, transport, biocompatibility, and toxicity of graphene derivatives in living systems and the natural environment.

  3. Cellulose binding domain proteins

    Energy Technology Data Exchange (ETDEWEB)

    Shoseyov, Oded (Karmey Yosef, IL); Shpiegl, Itai (Rehovot, IL); Goldstein, Marc (Davis, CA); Doi, Roy (Davis, CA)

    1998-01-01

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

  4. Sequential memory: Binding dynamics

    Science.gov (United States)

    Afraimovich, Valentin; Gong, Xue; Rabinovich, Mikhail

    2015-10-01

    Temporal order memories are critical for everyday animal and human functioning. Experiments and our own experience show that the binding or association of various features of an event together and the maintaining of multimodality events in sequential order are the key components of any sequential memories—episodic, semantic, working, etc. We study a robustness of binding sequential dynamics based on our previously introduced model in the form of generalized Lotka-Volterra equations. In the phase space of the model, there exists a multi-dimensional binding heteroclinic network consisting of saddle equilibrium points and heteroclinic trajectories joining them. We prove here the robustness of the binding sequential dynamics, i.e., the feasibility phenomenon for coupled heteroclinic networks: for each collection of successive heteroclinic trajectories inside the unified networks, there is an open set of initial points such that the trajectory going through each of them follows the prescribed collection staying in a small neighborhood of it. We show also that the symbolic complexity function of the system restricted to this neighborhood is a polynomial of degree L - 1, where L is the number of modalities.

  5. Lectin binding in meningiomas.

    Science.gov (United States)

    Kleinert, R; Radner, H

    1987-01-01

    Forty-two meningiomas of different morphological sub-type were examined to determine their pattern of binding to 11 different lectins which characterize cell surface components such as carbohydrate residues. Histiocytic and xanthoma cells within meningiomas could be demonstrated with six different lectins: wheat germ agglutinin (WGA), peanut agglutinin (PNA) Bauhinia purpurea agglutinin (BPA), Helix pomatia agglutinin (HPA), Vicia fava agglutinin (VFA) and Soyabean agglutinin (SBA). Vascular elements including endothelial cells and intimal cells, bound Ulex europaeus agglutinin type 1 (UEA 1), WGA and HPA. The fibrous stroma in fibrous and fibroblastic meningiomas bound PNA, Laburnum alpinum agglutinin (LAA) and SBA. Tumour cells in meningotheliomatous meningiomas and some areas of anaplastic meningiomas bound Concanavalin A, PNA, LAA and VFA whereas tumour cells in fibrous and fibroblastic meningiomas bound BPA, LAA and VFA. Lectin binding has proved to be of value in detecting histiocytic and xanthoma cells together with vascular elements within meningiomas. In addition, the different lectin binding patterns allow different histological sub-types of meningioma to be distinguished although the biological significance of the binding patterns is unclear. PMID:3658105

  6. Flexible Metal Oxide/Graphene Oxide Hybrid Neuromorphic Transistors on Flexible Conducting Graphene Substrates.

    Science.gov (United States)

    Wan, Chang Jin; Liu, Yang Hui; Feng, Ping; Wang, Wei; Zhu, Li Qiang; Liu, Zhao Ping; Shi, Yi; Wan, Qing

    2016-07-01

    Flexible metal oxide/graphene oxide hybrid multi-gate neuromorphic transistors are fabricated on flexible conducting graphene substrates. Dendritic integrations in both spatial and temporal modes are emulated, and spatiotemporal correlated logics are obtained. A proof-of-principle visual system model for emulating Lobula Giant Motion Detector neuron is also investigated. The results are of great significance for flexible sensors and neuromorphic cognitive systems. PMID:27159546

  7. DYNAMIC ANALYSIS OF FLEXIBLE-LINK AND FLEXIBLE-JOINT ROBOTS

    Institute of Scientific and Technical Information of China (English)

    ZHANG Ding-guo; ZHOU Sheng-feng

    2006-01-01

    The dynamic modeling and simulation of an N-flexible-link and N-flexiblejoint robot is reported. Each flexible joint is modeled as a linearly elastic torsional spring and the approach of assumed modes is adopted to describe the deformation of the flexiblelink. The complete governing equations of motion of the flexible-link-joint robots are derived via Kane's method. An illustrative example is given to validate the algorithm presented and to show the effects of flexibility on the dynamics of robots.

  8. Increasing flexibility of assets. Transition to flexible assets; Die steigende Bedeutung der Kraftwerksparkflexibilitaet

    Energy Technology Data Exchange (ETDEWEB)

    Aumueller, Adolf; Moik, Albert [EVN AG, Maria Enzersdorf (Austria); Rall, Hueseyin [STEAG GmbH, Herne (Germany)

    2016-07-01

    For the Energiewende flexibility is the key for the security of supply during the transition to an energy system based on renewables as well as for balancing the volatile generation in a renewable energy system. Storage is an integral module for delivering the flexibility needed by the future power system. Remaining R and D for storages and significant concession and building time for pump storage power plants lead to a time gap until storage is able to bear the brunt of delivering flexibility. The efficient and effective during the transition phase is the use of existing flexible power plants.

  9. Research into Flexibility Services. Final Report

    International Nuclear Information System (INIS)

    The Dutch Office for Energy Regulation (DTe) is currently investigating the Dutch gas flexibility market. DTe is concerned that Gasunie is dominant in the market. In order to take a view of Gasunie's market position, DTe needs to first define the market for gas flexibility services and then explore whether Gasunie is dominant in the market (or markets). DTe has commissioned Frontier to undertake the respective formal analysis. This report summarises the findings by Frontier. On the basis of this report and a formal consultation process, We follow a three-step approach to the study: (1) We first define the relevant markets for gas flexibility (Section 3); (2) We then analyse the structure of the markets for flexibility that we have defined (Section 4); (3) Finally, we assess whether Gasunie is dominant in the relevant markets, taking account of market shares and other competitive effects (Section 5). This document is the Final Report, which contains our views as to the market definition for gas flexibility and the position of Gasunie in the market. The remainder of this document is set out as follows: Section 2 provides an overview of aspects of the Dutch gas industry relevant to this study; Section 3 sets out our approach to defining the market and de-Mops our conclusions on the markets for gas flexibility; Section 4 provides our view as to the structure of the relevant flexibility markets as defined in Section 3; Section 5 reports our assessment as to whether Gasunie is dominant in the relevant markets, taking account of market shares and other competitive effects; Section 6 sets out our conclusions about the competitive assessment. We include three annexes that set out details related to the market definition and analysis of dominance

  10. Hip adductors' strength, flexibility, and injury risk.

    Science.gov (United States)

    Hrysomallis, Con

    2009-08-01

    The hip adductor muscle group plays an important role in both movement and stability at the hip joint in many athletic pursuits. Injury to this muscle group has been reported in a number of sports, among them, ice hockey, soccer, Australian football, and swimming. The identification of muscle characteristics that predispose a muscle to injury is an important step in developing conditioning programs to reduce injury risk. Muscle strength and range of motion are 2 parameters that may influence injury risk. The aim of this review was to examine the relationship between hip adductors' strength, flexibility, and injury risk. Strength testing has involved isokinetic or hand-held dynamometry. Flexibility has usually been assessed by goniometry during maximal hip abduction. An association has been reported between adductor strength deficits and injury for ice hockey players. Low adductor flexibility has also been identified as a risk factor for injury in soccer players. An intervention program that strengthened the hip adductors had some success in reducing injury risk for ice hockey players. There is some low- to moderate-level evidence from cohort studies to suggest that flexibility and strength are related to injury risk in particular sports and that an intervention program may be effective in reducing injury risk. Higher level evidence from randomized controlled trials is required to firmly establish the link between hip adductor flexibility, strength, and injury. PMID:19620912

  11. Flexible display technology for the objective force

    Science.gov (United States)

    Pellegrino, John M.; Wood, Gary L.; Morton, David C.; Forsythe, Eric W.; Girolamo, Henry J.

    2003-09-01

    The Army has initiated a flexible display research program. This program is part of the Army's strategy to create technologies that will enable revolutionary designs and transformational weapons systems for the Objective Force. The ARL flexible display program is more general than just for the dismounted soldier-it will also have implications for air and vehicular crews, and for the other services, even though it is not a DoD tri-service program per se. "Flexible" is defined in the program as displays that operate under conditions from conformal applications, limited flexing, to rollable displays for compact storage. The Army program will include display manufacturing concepts that enable roll-to-roll processes reduce cost, to tap a strong U.S. domestic industrial strength, and, eventually, to enable fabrication of very large sizes. There is commercial interest in flexible displays for applications ranging from wearable electronics for road-warriors and gamers to large screen 71-in. 1920x1200 color pixel consumer high definition television sets for walls. Industry willingness to cost share will be a key criterion in identifying investment opportunities that are necessary and timely from among all that may be envisioned. Some anticipated military applications and a roadmap are presented that identify the technology barriers at the materials, device and manufacturing levels to the creation of flexible display technology.

  12. Recent progress in flexible OLED displays

    Science.gov (United States)

    Hack, Michael G.; Weaver, Michael S.; Mahon, Janice K.; Brown, Julie J.

    2001-09-01

    Organic light emitting device (OLED) technology has recently been shown to demonstrate excellent performance and cost characteristics for use in numerous flat panel display (FPD) applications. OLED displays emit bright, colorful light with excellent power efficiency, wide viewing angle and video response rates. OLEDs are also demonstrating the requisite environmental robustness for a wide variety of applications. OLED technology is also the first FPD technology with the potential to be highly functional and durable in a flexible format. The use of plastic and other flexible substrate materials offers numerous advantages over commonly used glass substrates, including impact resistance, light weight, thinness and conformability. Currently, OLED displays are being fabricated on rigid substrates, such as glass or silicon wafers. At Universal Display Corporation (UDC), we are developing a new class of flexible OLED displays (FOLEDs). These displays also have extremely low power consumption through the use of electrophosphorescent doped OLEDs. To commercialize FOLED technology, a number of technical issues related to packaging and display processing on flexible substrates need to be addressed. In this paper, we report on our recent results to demonstrate the key technologies that enable the manufacture of power efficient, long-life flexible OLED displays for commercial and military applications.

  13. Global Analysis of a Flexible Riser

    Institute of Scientific and Technical Information of China (English)

    Liping Sun; Bo Qi

    2011-01-01

    The mechanical performance of a flexible riser is more outstanding than other risers in violent environmental conditions.Based on the lumped mass method,a steep wave flexible riser configuration attached to a Floating Production Storage and Offloading(FPSO)has been applied to a global analysis in order to acquire the static and dynamic behavior of the flexible riser.The riser was divided into a series of straight massless line segments with a node at each end.Only the axial and torsional properties of the line were modeled,while the mass,weight,and buoyancy were all lumped to the nodes.Four different buoyancy module lengths have been made to demonstrate the importance of mode selection,so as to confirm the optimum buoyancy module length.The results in the sensitivity study show that the flexible riser is not very sensitive to the ocean current,and the buoyancy module can reduce the Von Mises stress and improve the mechanical performance of the flexible riser.Shorter buoyancy module length can reduce the riser effective tension in a specific range of the buoyancy module length when other parameters are constant,but it can also increase the maximum curvature of the riser.As a result,all kinds of the riser performances should be taken into account in order to select the most appropriate buoyancy module length.

  14. Investigation of the flexibility of protein kinases implicated in the pathology of Alzheimer's disease.

    Science.gov (United States)

    Mazanetz, Michael P; Laughton, Charles A; Fischer, Peter M

    2014-01-01

    The pathological characteristics of Alzheimer's Disease (AD) have been linked to the activity of three particular kinases--Glycogen Synthase Kinase 3β (GSK3β), Cyclin-Dependent Kinase 5 (CDK5) and Extracellular-signal Regulated Kinase 2 (ERK2). As a consequence, the design of selective, potent and drug-like inhibitors of these kinases is of particular interest. Structure-based design methods are well-established in the development of kinase inhibitors. However, progress in this field is limited by the difficulty in obtaining X-ray crystal structures suitable for drug design and by the inability of this method to resolve highly flexible regions of the protein that are crucial for ligand binding. To address this issue, we have undertaken a study of human protein kinases CDK5/p25, CDK5, ERK2 and GSK3β using both conventional molecular dynamics (MD) and the new Active Site Pressurisation (ASP) methodology, to look for kinase-specific patterns of flexibility that could be leveraged for the design of selective inhibitors. ASP was used to examine the intrinsic flexibility of the ATP-binding pocket for CDK5/p25, CDK5 and GSK3β where it is shown to be capable of inducing significant conformational changes when compared with X-ray crystal structures. The results from these experiments were used to quantify the dynamics of each protein, which supported the observations made from the conventional MD simulations. Additional information was also derived from the ASP simulations, including the shape of the ATP-binding site and the rigidity of the ATP-binding pocket. These observations may be exploited in the design of selective inhibitors of GSK3β, CDK5 and ERK2. PMID:24983862

  15. Investigation of the Flexibility of Protein Kinases Implicated in the Pathology of Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Michael P. Mazanetz

    2014-06-01

    Full Text Available The pathological characteristics of Alzheimer’s Disease (AD have been linked to the activity of three particular kinases—Glycogen Synthase Kinase 3β (GSK3β, Cyclin-Dependent Kinase 5 (CDK5 and Extracellular-signal Regulated Kinase 2 (ERK2. As a consequence, the design of selective, potent and drug-like inhibitors of these kinases is of particular interest. Structure-based design methods are well-established in the development of kinase inhibitors. However, progress in this field is limited by the difficulty in obtaining X-ray crystal structures suitable for drug design and by the inability of this method to resolve highly flexible regions of the protein that are crucial for ligand binding. To address this issue, we have undertaken a study of human protein kinases CDK5/p25, CDK5, ERK2 and GSK3β using both conventional molecular dynamics (MD and the new Active Site Pressurisation (ASP methodology, to look for kinase-specific patterns of flexibility that could be leveraged for the design of selective inhibitors. ASP was used to examine the intrinsic flexibility of the ATP-binding pocket for CDK5/p25, CDK5 and GSK3β where it is shown to be capable of inducing significant conformational changes when compared with X-ray crystal structures. The results from these experiments were used to quantify the dynamics of each protein, which supported the observations made from the conventional MD simulations. Additional information was also derived from the ASP simulations, including the shape of the ATP-binding site and the rigidity of the ATP-binding pocket. These observations may be exploited in the design of selective inhibitors of GSK3β, CDK5 and ERK2.

  16. Flexible barrier technology for enabling rollable AMOLED displays and upscaling flexible OLED lighting

    NARCIS (Netherlands)

    Li, F.M.; Unnikrishnan, S.; Weijer, P. van de; Assche, F. van; Shen, J.; Ellis, T.; Manders, W.; Akkerman, H.; Bouten, P.; Mol, A.M.B. van

    2013-01-01

    The availability of a high performance thin-film barrier is the most critical challenge in upscaling and commercializing flexible OLED products. We report a flexible thin-film-barrier technology that meets lifetime specifications for OLED lighting, and demonstrate it in rollable QVGA a-IGZO AMOLED d

  17. Development of the Coping Flexibility Scale: Evidence for the Coping Flexibility Hypothesis

    Science.gov (United States)

    Kato, Tsukasa

    2012-01-01

    "Coping flexibility" was defined as the ability to discontinue an ineffective coping strategy (i.e., evaluation coping) and produce and implement an alternative coping strategy (i.e., adaptive coping). The Coping Flexibility Scale (CFS) was developed on the basis of this definition. Five studies involving approximately 4,400 Japanese college…

  18. Flexible Pedagogies: Employer Engagement and Work-Based Learning. Flexible Pedagogies: Preparing for the Future Series

    Science.gov (United States)

    Kettle, Jane

    2013-01-01

    This publication focuses on national and international policy initiatives to develop a better understanding of work-based learners and the types of flexibility that may well enhance their study especially pedagogically. As part of our five-strand research project "Flexible Pedagogies: preparing for the future" it: (1) highlights the…

  19. Flexible Programmes in Higher Professional Education: Expert Validation of a Flexible Educational Model

    Science.gov (United States)

    Schellekens, Ad; Paas, Fred; Verbraeck, Alexander; van Merrienboer, Jeroen J. G.

    2010-01-01

    In a preceding case study, a process-focused demand-driven approach for organising flexible educational programmes in higher professional education (HPE) was developed. Operations management and instructional design contributed to designing a flexible educational model by means of discrete-event simulation. Educational experts validated the model…

  20. Becoming more systematic about flexible learning: Beyond time and distance.

    NARCIS (Netherlands)

    Boer, de Wim; Collis, Betty

    2005-01-01

    Changes in higher education frequently involve the need for more flexibility in course design and delivery. Flexibility is a concept that can be operationalized in many ways. One approach to conceptualizing flexibility within courses is to distinguish planning-type flexibility, which the instructor

  1. Becoming More Systematic about Flexible Learning: Beyond Time and Distance

    Science.gov (United States)

    de Boer, Wim; Collis, Betty

    2005-01-01

    Changes in higher education frequently involve the need for more flexibility in course design and delivery. Flexibility is a concept that can be operationalized in many ways. One approach to conceptualizing flexibility within courses is to distinguish planning-type flexibility, which the instructor can designate before the course begins and which…

  2. Flexible Labour Strategy in the Dutch Automotive Industry

    NARCIS (Netherlands)

    Riemsdijk, van Maarten; Leede, de Jan

    2001-01-01

    Labour flexibility is a major way for companies to become more flexible. Why companies use flexible labour relations varies widely per industry. We assess the development of labour flexibility within the Dutch automotive industry. Four cases, together representing the production chain, are presented

  3. Reflection-Based Python-C++ Bindings

    International Nuclear Information System (INIS)

    Python is a flexible, powerful, high-level language with excellent interactive and introspective capabilities and a very clean syntax. As such, it can be a very effective tool for driving physics analysis. Python is designed to be extensible in low-level C-like languages, and its use as a scientific steering language has become quite widespread. To this end, existing and custom-written C or C++ libraries are bound to the Python environment as so-called extension modules. A number of tools for easing the process of creating such bindings exist, such as SWIG and Boost. Python. Yet, the process still requires a considerable amount of effort and expertise. The C++ language has few built-in introspective capabilities, but tools such as LCGDict and CINT add this by providing so-called dictionaries: libraries that contain information about the names, entry points, argument types, etc. of other libraries. The reflection information from these dictionaries can be used for the creation of bindings and so the process can be fully automated, as dictionaries are already provided for many end-user libraries for other purposes, such as object persistency. PyLCGDict is a Python extension module that uses LCG dictionaries, as PyROOT uses CINT reflection information, to allow /cwPython users to access C++ libraries with essentially no preparation on the users' behalf. In addition, and in a similar way, PyROOT gives ROOT users access to Python libraries

  4. Solution measurement of DNA curvature in papillomavirus E2 binding sites

    OpenAIRE

    Zimmerman, Jeff M.; Maher, L. James

    2003-01-01

    ‘Indirect readout’ refers to the proposal that proteins can recognize the intrinsic three-dimensional shape or flexibility of a DNA binding sequence apart from direct protein contact with DNA base pairs. The differing affinities of human papillomavirus (HPV) E2 proteins for different E2 binding sites have been proposed to reflect indirect readout. DNA bending has been observed in X-ray structures of E2 protein–DNA complexes. X-ray structures of three different E2 DNA binding sites revealed di...

  5. Using remote substituents to control solution structure and anion binding in lanthanide complexes

    DEFF Research Database (Denmark)

    Tropiano, Manuel; Blackburn, Octavia A.; Tilney, James A.;

    2013-01-01

    of the molecule, at a substantial distance from the binding pocket. Herein, we explore these remote substituent effects and explain the observed behaviour through discussion of the way in which remote substituents can influence and control the global structure of a molecule through their demands upon...... conformational space. Peripheral modifications to a binuclear lanthanide motif derived from α,α'-bis(DO3 Ayl)-m-xylene are shown to result in dramatic changes to the binding constant for isophthalate. In this system, the parent compound displays considerable conformational flexibility, yet can be assumed to bind...

  6. Dynamic Scheduling of Flexible Job Shops

    Institute of Scientific and Technical Information of China (English)

    SHAHID Ikramullah Butt; SUN Hou-fang

    2007-01-01

    Aim of this research is to minimize makespan in the flexible job shop environment by the use of genetic algorithms and scheduling rules.Software is developed using genetic algorithms and scheduling rules based on certain constraints such as non-preemption of jobs,recirculation,set up times,non-breakdown of machines etc.Purpose of the software is to develop a schedule for flexible job shop environment,which is a special case of job shop scheduling problem.Scheduling algorithm used in the software is verified and tested by using MT10 as benchmark problem,presented in the flexible job shop environment at the end.LEKIN(R) software results are also compared with results of the developed software by the use of MT10 benchmark problem to show that the latter is a practical software and can be used successfully at BIT Training Workshop.

  7. Implications of resistance exercise practice to flexibility

    Directory of Open Access Journals (Sweden)

    Cristiane Eri Shiromoto

    2008-06-01

    Full Text Available The aim of this paper is to compare the degrees of flexibility in resistance exercise practitioners before and after a period of six months and verify the relationship between the data and the individuals’ life style. A descriptive method was used for a sample of 46 individuals from Action Academia de Maringá – Pr. The data were collected in Sptember / 2000 and March / 2001 through their frequency and evaluation files and also a goniometer to check the ischia extention. Through the ‘t’ test a significant increase in both male and female flexibility was observed. The style of life and profession may interfere in a negative way although the regular and simultaneous practice of resistance and stretching exercises seem to be a predominant factor in developing flexibility and in physical aptitude favourable degrees for health and life quality.

  8. Analytical and Numerical Modeling for Flexible Pipes

    Institute of Scientific and Technical Information of China (English)

    WANG Wei; CHEN Geng

    2011-01-01

    The unbonded flexible pipe of eight layers,in which all the layers except the carcass layer are assumed to have isotropic properties,has been analyzed.Specifically,the carcass layer shows the orthotropic characteristics.The effective elastic moduli of the carcass layer have been developed in terms of the influence of deformation to stiffness.With consideration of the effective elastic moduli,the structure can be properly analyzed.Also the relative movements of tendons and relative displacements of wires in helical armour layer have been investigated.A three-dimensional nonlinear finite element model has been presented to predict the response of flexible pipes under axial force and torque.Further,the friction and contact of interlayer have been considered.Comparison between the finite element model and experimental results obtained in literature has been given and discussed,which might provide practical and technical support for the application of unbonded flexible pipes.

  9. Flexible Electronics Development Supported by NASA

    Science.gov (United States)

    Baumann, Eric

    2014-01-01

    The commercial electronics industry is leading development in most areas of electronics for NASA applications; however, working in partnership with industry and the academic community, results from NASA research could lead to better understanding and utilization of electronic materials by the flexible electronics industry. Innovative ideas explored by our partners in industry and the broader U.S. research community help NASA execute our missions and bring new American products and services to the global technology marketplace. [Mike Gazarik, associate administrator for Space Technology, NASA Headquarters, Washington DC] This presentation provides information on NASA needs in electronics looking towards the future, some of the work being supported by NASA in flexible electronics, and the capabilities of the Glenn Research Center supporting the development of flexible electronics.

  10. Demand flexibility from residential heat pump

    DEFF Research Database (Denmark)

    Bhattarai, Bishnu Prasad; Bak-Jensen, Birgitte; Pillai, Jayakrishnan Radhakrishna;

    2014-01-01

    Demand response (DR) is considered as a potentially effective tool to compensate generation intermittency imposed by renewable sources. Further, DR can instigate to offer optimum asset utilization and to avoid or delay the need for new infrastructure investment. Being a sizable load together...... with high thermal time constant, heat pumps (HP) can offer a great deal of flexibility in the future intelligent grids especially to compensate fluctuating generation. However, the HP flexibility is highly dependent on thermal demand profile, namely hot water and space heating demand. This paper proposes...... price based scheduling followed by a demand dispatch based central control and a local voltage based adaptive control, to realize HP demand flexibility. Two-step control architecture, namely local primary control encompassed by the central coordinative control, is proposed to implement...

  11. Creating flexible work arrangements through idiosyncratic deals.

    Science.gov (United States)

    Hornung, Severin; Rousseau, Denise M; Glaser, Jürgen

    2008-05-01

    A survey of 887 employees in a German government agency assessed the antecedents and consequences of idiosyncratic arrangements individual workers negotiated with their supervisors. Work arrangements promoting the individualization of employment conditions, such as part-time work and telecommuting, were positively related to the negotiation of idiosyncratic deals ("i-deals"). Worker personal initiative also had a positive effect on i-deal negotiation. Two types of i-deals were studied: flexibility in hours of work and developmental opportunities. Flexibility i-deals were negatively related and developmental i-deals positively related to work-family conflict and working unpaid overtime. Developmental i-deals were also positively related to increased performance expectations and affective organizational commitment, while flexibility i-deals were unrelated to either. PMID:18457493

  12. Tuned mass absorber on a flexible structure

    DEFF Research Database (Denmark)

    Krenk, Steen; Høgsberg, Jan Becker

    2014-01-01

    The classic design of a tuned mass absorber is based on a simple two-mass analogy in which the tuned mass is connected to the structural mass with a spring and a viscous damper. In a flexible multi-degree-of-freedom structure the tuned mass absorber is typically introduced to provide damping...... of a specific mode. The motion of the point of attachment of the tuned mass absorber to the structure has not only a contribution from the targeted mode, but also a background contribution from other non-resonant modes. Similarly, the force provided by the tuned mass absorber is distributed between the targeted...... with the desired maximum amplification, from which the device damper, mass and stiffness are determined, accounting for the background flexibility. Examples demonstrate the influence of the flexibility effect and the efficiency of the proposed procedure....

  13. Subsea flexible flowline installation issues and solutions

    Institute of Scientific and Technical Information of China (English)

    Kevin Huang

    2013-01-01

    Flexible flowlines and risers have been increasingly used for deepwater and ultra-deepwater field applications,partially because of its low submerged weight and better dynamic characteristics comparing to rigid pipelines.The offshore installation of flowline may have advantages as well.However,it has special needs for the installation aids,and it is challenging to install tie-in structures due to its low bending stiffness.This paper is to present some of the challenges during a recent flexible installation project with a total of more than 100 km flexible flowlines,and 24 in-line sleds/pipeline end termination(PLET) in water depth up to 1 300 m.

  14. Plasma jet printing for flexible substrates

    Science.gov (United States)

    Gandhiraman, Ram P.; Singh, Eric; Diaz-Cartagena, Diana C.; Nordlund, Dennis; Koehne, Jessica; Meyyappan, M.

    2016-03-01

    Recent interest in flexible electronics and wearable devices has created a demand for fast and highly repeatable printing processes suitable for device manufacturing. Robust printing technology is critical for the integration of sensors and other devices on flexible substrates such as paper and textile. An atmospheric pressure plasma-based printing process has been developed to deposit different types of nanomaterials on flexible substrates. Multiwalled carbon nanotubes were deposited on paper to demonstrate site-selective deposition as well as direct printing without any type of patterning. Plasma-printed nanotubes were compared with non-plasma-printed samples under similar gas flow and other experimental conditions and found to be denser with higher conductivity. The utility of the nanotubes on the paper substrate as a biosensor and chemical sensor was demonstrated by the detection of dopamine, a neurotransmitter, and ammonia, respectively.

  15. A flexible infrared sensor for tissue oximetry

    DEFF Research Database (Denmark)

    Petersen, Søren Dahl; Thyssen, Anders; Engholm, Mathias;

    2013-01-01

    We present a flexible infrared sensor for use in tissue oximetry with the aim of treating prematurely born infants. The sensor will detect the oxygen saturation in brain tissue through near infrared spectroscopy. The sensor itself consists of several individual silicon photo detectors fully...... integrated in a flexible array. The flexibility is achieved by combining silicon with Polydimethylsiloxane and polyimide using standard IC manufacturing. This ensures that the electrical interconnects on the sensor can withstand being bent in order for the sensor to confine to the curved surface of the head...... of a neonatal. The sensor platform has been tested and is found to be very durable and capable of being both bent to small radii of curvature and strained in the longitudinal direction. The electrical interconnects on the sensor only experience a relative small increase in resistance when the sensor is bent up...

  16. Flexible Developing System for Modern Instrument Manufacturing

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The modern instrument manufacturing has many features, such as high technologies, multiple varieties and small quantities. Aiming at those features, an instrumentation flexible developing system (IFDS) is presented. It constitutes a kind of opening, compatible, extensible and upgradeable flexible developing system, and it will offer a kind of technology equipment for the research and development of new modern instrument products. Its flexible mechanism is able to be suited for different and special requirements of many instrument systems, and its system integrated mechanism is able to adapt to common technological features of most instrument systems. It is IFDS that makes it easy to accomplish a quick system integration of instrument products. IFDS solves key technological problems related to modern instruments development, develops multiple systems for modern instrument development and accomplishes rapid development of series of new products.

  17. Printed electronic on flexible and glass substrates

    Science.gov (United States)

    Futera, Konrad; Jakubowska, Małgorzata; Kozioł, Grażyna

    2010-09-01

    Organic electronics is a platform technology that enables multiple applications based on organic electronics but varied in specifications. Organic electronics is based on the combination of new materials and cost-effective, large area production processes that provide new fields of application. Organic electronic by its size, weight, flexibility and environmental friendliness electronics enables low cost production of numerous electrical components and provides for such promising fields of application as: intelligent packaging, low cost RFID, flexible solar cells, disposable diagnostic devices or games, and printed batteries [1]. The paper presents results of inkjetted electronics elements on flexible and glass substrates. The investigations was target on characterizing shape, surface and geometry of printed structures. Variety of substrates were investigated, within some, low cost, non specialized substrate, design for other purposes than organic electronic.

  18. Recent progress of flexible AMOLED displays

    Science.gov (United States)

    Pang, Huiqing; Rajan, Kamala; Silvernail, Jeff; Mandlik, Prashant; Ma, Ruiqing; Hack, Mike; Brown, Julie J.; Yoo, Juhn S.; Jung, Sang-Hoon; Kim, Yong-Cheol; Byun, Seung-Chan; Kim, Jong-Moo; Yoon, Soo-Young; Kim, Chang-Dong; Hwang, Yong-Kee; Chung, In-Jae; Fletcher, Mark; Green, Derek; Pangle, Mike; McIntyre, Jim; Smith, Randal D.

    2011-03-01

    Significant progress has been made in recent years in flexible AMOLED displays and numerous prototypes have been demonstrated. Replacing rigid glass with flexible substrates and thin-film encapsulation makes displays thinner, lighter, and non-breakable - all attractive features for portable applications. Flexible AMOLEDs equipped with phosphorescent OLEDs are considered one of the best candidates for low-power, rugged, full-color video applications. Recently, we have demonstrated a portable communication display device, built upon a full-color 4.3-inch HVGA foil display with a resolution of 134 dpi using an all-phosphorescent OLED frontplane. The prototype is shaped into a thin and rugged housing that will fit over a user's wrist, providing situational awareness and enabling the wearer to see real-time video and graphics information.

  19. Stochastic Dynamics Underlying Cognitive Stability and Flexibility.

    Directory of Open Access Journals (Sweden)

    Kai Ueltzhöffer

    2015-06-01

    Full Text Available Cognitive stability and flexibility are core functions in the successful pursuit of behavioral goals. While there is evidence for a common frontoparietal network underlying both functions and for a key role of dopamine in the modulation of flexible versus stable behavior, the exact neurocomputational mechanisms underlying those executive functions and their adaptation to environmental demands are still unclear. In this work we study the neurocomputational mechanisms underlying cue based task switching (flexibility and distractor inhibition (stability in a paradigm specifically designed to probe both functions. We develop a physiologically plausible, explicit model of neural networks that maintain the currently active task rule in working memory and implement the decision process. We simplify the four-choice decision network to a nonlinear drift-diffusion process that we canonically derive from a generic winner-take-all network model. By fitting our model to the behavioral data of individual subjects, we can reproduce their full behavior in terms of decisions and reaction time distributions in baseline as well as distractor inhibition and switch conditions. Furthermore, we predict the individual hemodynamic response timecourse of the rule-representing network and localize it to a frontoparietal network including the inferior frontal junction area and the intraparietal sulcus, using functional magnetic resonance imaging. This refines the understanding of task-switch-related frontoparietal brain activity as reflecting attractor-like working memory representations of task rules. Finally, we estimate the subject-specific stability of the rule-representing attractor states in terms of the minimal action associated with a transition between different rule states in the phase-space of the fitted models. This stability measure correlates with switching-specific thalamocorticostriatal activation, i.e., with a system associated with flexible working memory

  20. Stochastic Dynamics Underlying Cognitive Stability and Flexibility.

    Science.gov (United States)

    Ueltzhöffer, Kai; Armbruster-Genç, Diana J N; Fiebach, Christian J

    2015-06-01

    Cognitive stability and flexibility are core functions in the successful pursuit of behavioral goals. While there is evidence for a common frontoparietal network underlying both functions and for a key role of dopamine in the modulation of flexible versus stable behavior, the exact neurocomputational mechanisms underlying those executive functions and their adaptation to environmental demands are still unclear. In this work we study the neurocomputational mechanisms underlying cue based task switching (flexibility) and distractor inhibition (stability) in a paradigm specifically designed to probe both functions. We develop a physiologically plausible, explicit model of neural networks that maintain the currently active task rule in working memory and implement the decision process. We simplify the four-choice decision network to a nonlinear drift-diffusion process that we canonically derive from a generic winner-take-all network model. By fitting our model to the behavioral data of individual subjects, we can reproduce their full behavior in terms of decisions and reaction time distributions in baseline as well as distractor inhibition and switch conditions. Furthermore, we predict the individual hemodynamic response timecourse of the rule-representing network and localize it to a frontoparietal network including the inferior frontal junction area and the intraparietal sulcus, using functional magnetic resonance imaging. This refines the understanding of task-switch-related frontoparietal brain activity as reflecting attractor-like working memory representations of task rules. Finally, we estimate the subject-specific stability of the rule-representing attractor states in terms of the minimal action associated with a transition between different rule states in the phase-space of the fitted models. This stability measure correlates with switching-specific thalamocorticostriatal activation, i.e., with a system associated with flexible working memory updating and

  1. Movable MEMS Devices on Flexible Silicon

    KAUST Repository

    Ahmed, Sally

    2013-05-05

    Flexible electronics have gained great attention recently. Applications such as flexible displays, artificial skin and health monitoring devices are a few examples of this technology. Looking closely at the components of these devices, although MEMS actuators and sensors can play critical role to extend the application areas of flexible electronics, fabricating movable MEMS devices on flexible substrates is highly challenging. Therefore, this thesis reports a process for fabricating free standing and movable MEMS devices on flexible silicon substrates; MEMS flexure thermal actuators have been fabricated to illustrate the viability of the process. Flexure thermal actuators consist of two arms: a thin hot arm and a wide cold arm separated by a small air gap; the arms are anchored to the substrate from one end and connected to each other from the other end. The actuator design has been modified by adding etch holes in the anchors to suit the process of releasing a thin layer of silicon from the bulk silicon substrate. Selecting materials that are compatible with the release process was challenging. Moreover, difficulties were faced in the fabrication process development; for example, the structural layer of the devices was partially etched during silicon release although it was protected by aluminum oxide which is not attacked by the releasing gas . Furthermore, the thin arm of the thermal actuator was thinned during the fabrication process but optimizing the patterning and etching steps of the structural layer successfully solved this problem. Simulation was carried out to compare the performance of the original and the modified designs for the thermal actuators and to study stress and temperature distribution across a device. A fabricated thermal actuator with a 250 μm long hot arm and a 225 μm long cold arm separated by a 3 μm gap produced a deflection of 3 μm before silicon release, however, the fabrication process must be optimized to obtain fully functioning

  2. Tactical supply chain planning models with inherent flexibility

    DEFF Research Database (Denmark)

    Esmaeilikia, Masoud; Fahimnia, Behnam; Sarkis, Joeseph;

    2016-01-01

    Supply chains (SCs) can be managed at many levels. The use of tactical SC planning models with multiple flexibility options can help manage the usual operations efficiently and effectively, whilst improve the SC resiliency in response to inherent environmental uncertainties. This paper defines...... tactical SC flexibility and identifies tactical flexibility measures and options for development of flexible SC planning models. A classification of the existing literature of SC planning is introduced that highlights the characteristics of published flexibility inclusive models. Additional classifications...

  3. Innovation,Flexibility, Change-Premises of Organizational Development

    OpenAIRE

    Amalia Venera TODORUT

    2008-01-01

    The features of innovation, flexibility and change mutually influence one another. Provided that change is perceived as a feature leading to innovation, flexibility is the feature that enables it. Innovation cannot exist without change but nonetheless each and every change leads to innovation. Flexibility is a necessary condition but not sufficient for the innovation since it is influenced by change and balanced by flexibility. This fact suggests that the flexible companies lead to a more sig...

  4. Innovation in wearable and flexible antennas

    CERN Document Server

    Khaleel, Haider

    2014-01-01

    This book deals with the design, numerical simulation, state of the art fabrication processes and methods, qualitative and quantitative tests, and measurement techniques of wearable and flexible antennas of different topologies, such as: Planar Inverted F, Printed Monopoles, Micropoles and Microstrips. Novel trends, materials, and fabrication and measurement techniques used in this vital field of antenna systems are also discussed.To the best of the editor's knowledge, at the time of publication, there are no published books targeting the vital topic of flexible antennas specifically and/or se

  5. Fabrication of SWCNT based flexible chemiresistor

    Science.gov (United States)

    Rajput, Mayank; Kaur, Rajvinder; Das, S.; Kumar, Anil

    2016-04-01

    Carboxyl (-COOH) functionalized SWCNT chemiresistors have been realized on Kapton substrate patterned with Au microelectrodes by the drop casting of functionalized SWCNT dispersion in DI water. I-V measurements on fabricated chemiresistor showed ohmic behavior at different temperatures (25°C-120°C). The effect of bending on flexible functionalized SWCNT chemiresistor for different diameter has been measured. It has been found that bending at different radius of curvature doesn't change the ohmic behavior of fabricated chemiresistor. Achieved results are promising for cheap flexible electronic devices.

  6. Flexible Polyhedral Surfaces with Two Flat Poses

    Directory of Open Access Journals (Sweden)

    Hellmuth Stachel

    2015-05-01

    Full Text Available We present three types of polyhedral surfaces, which are continuously flexible and have not only an initial pose, where all faces are coplanar, but pass during their self-motion through another pose with coplanar faces (“flat pose”. These surfaces are examples of so-called rigid origami, since we only admit exact flexions, i.e., each face remains rigid during the motion; only the dihedral angles vary. We analyze the geometry behind Miura-ori and address Kokotsakis’ example of a flexible tessellation with the particular case of a cyclic quadrangle. Finally, we recall Bricard’s octahedra of Type 3 and their relation to strophoids.

  7. Flexible pavement performance evaluation using deflection criteria

    Science.gov (United States)

    Wedner, R. J.

    1980-04-01

    Flexible pavement projects in Nebraska were monitored for dynamic deflections, roughness, and distress for six consecutive years. Present surface conditions were characterized and data for evaluating rehabilitation needs, including amount of overlay, were provided. Data were evaluated and factors were isolated for determining the structural adequacy of flexible pavements, evaluating existing pavement strength and soil subgrade conditions, and determining overlay thickness requirements. Terms for evaluating structural condition for pavement sufficiently ratings were developed and existing soil support value and subgrade strength province maps were evaluated.

  8. Mechanistic design concepts for conventional flexible pavements

    Science.gov (United States)

    Elliott, R. P.; Thompson, M. R.

    1985-02-01

    Mechanical design concepts for convetional flexible pavement (asphalt concrete (AC) surface plus granular base/subbase) for highways are proposed and validated. The procedure is based on ILLI-PAVE, a stress dependent finite element computer program, coupled with appropriate transfer functions. Two design criteria are considered: AC flexural fatigue cracking and subgrade rutting. Algorithms were developed relating pavement response parameters (stresses, strains, deflections) to AC thickness, AC moduli, granular layer thickness, and subgrade moduli. Extensive analyses of the AASHO Road Test flexible pavement data are presented supporting the validity of the proposed concepts.

  9. Adaptive Fuzzy Attitude Control of Flexible Satellite

    Institute of Scientific and Technical Information of China (English)

    GUAN Ping; LIU Xiang-dong; CHEN Jia-bin

    2005-01-01

    The adaptive fuzzy control is applied in the attitude stabilization of flexible satellite. The detailed design procedure of the adaptive fuzzy control system is presented. Two T-S models are used as both controller and identifier. The parameters of the controller could be modified according to the information of the identifier. Simulation results show that the method can effectively cope with the uncertainty of flexible satellite by on-line learning and thus posses the good robustness. With the proposed method, the precise attitude control is accomplished.

  10. Flexible input, dazzling output with IBM i

    CERN Document Server

    Victória-Pereira, Rafael

    2014-01-01

    Link your IBM i system to the modern business server world! This book presents easier and more flexible ways to get data into your IBM i system, along with rather surprising methods to export and present the vital business data it contains. You'll learn how to automate file transfers, seamlessly connect PC applications with your RPG programs, and much more. Input operations will become more flexible and user-proof, with self-correcting import processes and direct file transfers that require a minimum of user intervention. Also learn novel ways to present information: your DB2 data will look gr

  11. Flexible robotics applications to multiscale manipulations

    CERN Document Server

    Grossard , Mathieu; Regnier, Stephane

    2013-01-01

    The objective of this book is to provide those interested in the field of flexible robotics with an overview of several scientific and technological advances in the practical field of robotic manipulation. The different chapters examine various stages that involve a number of robotic devices, particularly those designed for manipulation tasks characterized by mechanical flexibility. Chapter 1 deals with the general context surrounding the design of functionally integrated microgripping systems. Chapter 2 focuses on the dual notations of modal commandability and observability, which play a sig

  12. ANFIS Modelling of Flexible Plate Structure

    Directory of Open Access Journals (Sweden)

    A. A. M. Al-Khafaji

    2010-06-01

    Full Text Available This paper presented an investigation into the performance of system identification using an Adaptive Neuro-Fuzzy Inference System (ANFIS technique for the dynamic modelling of a twodimensional flexible plate structure. It is confirmed experimentally, using National Instrumentation (NI Data Acquisition System (DAQ and flexible plate test rig that ANFIS can be effectively used for modelling the system with highly accurate results. The accuracy of the modelling results is demonstrated through validation tests including training and test validation and correlation tests.

  13. New binding site conformations of the dengue virus NS3 protease accessed by molecular dynamics simulation.

    Directory of Open Access Journals (Sweden)

    Hugo de Almeida

    Full Text Available Dengue fever is caused by four distinct serotypes of the dengue virus (DENV1-4, and is estimated to affect over 500 million people every year. Presently, there are no vaccines or antiviral treatments for this disease. Among the possible targets to fight dengue fever is the viral NS3 protease (NS3PRO, which is in part responsible for viral processing and replication. It is now widely recognized that virtual screening campaigns should consider the flexibility of target protein by using multiple active conformational states. The flexibility of the DENV NS3PRO could explain the relatively low success of previous virtual screening studies. In this first work, we explore the DENV NS3PRO conformational states obtained from molecular dynamics (MD simulations to take into account protease flexibility during the virtual screening/docking process. To do so, we built a full NS3PRO model by multiple template homology modeling. The model comprised the NS2B cofactor (essential to the NS3PRO activation, a glycine flexible link and the proteolytic domain. MD simulations had the purpose to sample, as closely as possible, the ligand binding site conformational landscape prior to inhibitor binding. The obtained conformational MD sample was clustered into four families that, together with principal component analysis of the trajectory, demonstrated protein flexibility. These results allowed the description of multiple binding modes for the Bz-Nle-Lys-Arg-Arg-H inhibitor, as verified by binding plots and pair interaction analysis. This study allowed us to tackle protein flexibility in our virtual screening campaign against the dengue virus NS3 protease.

  14. Megalin binds and mediates cellular internalization of folate binding protein

    DEFF Research Database (Denmark)

    Birn, Henrik; Zhai, Xiaoyue; Holm, Jan;

    2005-01-01

    Folate is an essential vitamin involved in a number of biological processes. High affinity folate binding proteins (FBPs) exist both as glycosylphosphatidylinositol-linked, membrane associated folate binding proteins and as soluble FBPs in plasma and some secretory fluids such as milk, saliva...... to bind and mediate cellular uptake of FBP. Surface plasmon resonance analysis shows binding of bovine and human milk FBP to immobilized megalin, but not to low density lipoprotein receptor related protein. Binding of (125)I-labeled folate binding protein (FBP) to sections of kidney proximal tubule, known...... to express high levels of megalin, is inhibitable by excess unlabeled FBP and by receptor associated protein, a known inhibitor of binding to megalin. Immortalized rat yolk sac cells, representing an established model for studying megalin-mediated uptake, reveal (125)I-labeled FBP uptake which is inhibited...

  15. SCOWLP classification: Structural comparison and analysis of protein binding regions

    Directory of Open Access Journals (Sweden)

    Anders Gerd

    2008-01-01

    Full Text Available Abstract Background Detailed information about protein interactions is critical for our understanding of the principles governing protein recognition mechanisms. The structures of many proteins have been experimentally determined in complex with different ligands bound either in the same or different binding regions. Thus, the structural interactome requires the development of tools to classify protein binding regions. A proper classification may provide a general view of the regions that a protein uses to bind others and also facilitate a detailed comparative analysis of the interacting information for specific protein binding regions at atomic level. Such classification might be of potential use for deciphering protein interaction networks, understanding protein function, rational engineering and design. Description Protein binding regions (PBRs might be ideally described as well-defined separated regions that share no interacting residues one another. However, PBRs are often irregular, discontinuous and can share a wide range of interacting residues among them. The criteria to define an individual binding region can be often arbitrary and may differ from other binding regions within a protein family. Therefore, the rational behind protein interface classification should aim to fulfil the requirements of the analysis to be performed. We extract detailed interaction information of protein domains, peptides and interfacial solvent from the SCOWLP database and we classify the PBRs of each domain family. For this purpose, we define a similarity index based on the overlapping of interacting residues mapped in pair-wise structural alignments. We perform our classification with agglomerative hierarchical clustering using the complete-linkage method. Our classification is calculated at different similarity cut-offs to allow flexibility in the analysis of PBRs, feature especially interesting for those protein families with conflictive binding regions

  16. Glycosylation of Thermomyces lanuginosa lipase enhances surface binding towards phospholipids, but does not significantly influence the catalytic activity

    DEFF Research Database (Denmark)

    Peters, Günther H.J.; Svendsen, Allan; Langbjerg, H.;

    2002-01-01

    or PG matrix than Tll. Addition of the substrate analog benzene boronic acid (BBA) increases the binding affinity of the S146A and N33Q mutants, while only small changes are observed for Tll suggesting that the dynamics of the active-site lid influences the binding affinity and that the flexibility...

  17. Carboplatin binding to histidine

    Energy Technology Data Exchange (ETDEWEB)

    Tanley, Simon W. M. [University of Manchester, Brunswick Street, Manchester M13 9PL (United Kingdom); Diederichs, Kay [University of Konstanz, D-78457 Konstanz (Germany); Kroon-Batenburg, Loes M. J. [Utrecht University, Padualaan 8, 3584 CH Utrecht (Netherlands); Levy, Colin [University of Manchester, 131 Princess Street, Manchester M1 7DN (United Kingdom); Schreurs, Antoine M. M. [Utrecht University, Padualaan 8, 3584 CH Utrecht (Netherlands); Helliwell, John R., E-mail: john.helliwell@manchester.ac.uk [University of Manchester, Brunswick Street, Manchester M13 9PL (United Kingdom)

    2014-08-29

    An X-ray crystal structure showing the binding of purely carboplatin to histidine in a model protein has finally been obtained. This required extensive crystallization trials and various novel crystal structure analyses. Carboplatin is a second-generation platinum anticancer agent used for the treatment of a variety of cancers. Previous X-ray crystallographic studies of carboplatin binding to histidine (in hen egg-white lysozyme; HEWL) showed the partial conversion of carboplatin to cisplatin owing to the high NaCl concentration used in the crystallization conditions. HEWL co-crystallizations with carboplatin in NaBr conditions have now been carried out to confirm whether carboplatin converts to the bromine form and whether this takes place in a similar way to the partial conversion of carboplatin to cisplatin observed previously in NaCl conditions. Here, it is reported that a partial chemical transformation takes place but to a transplatin form. Thus, to attempt to resolve purely carboplatin binding at histidine, this study utilized co-crystallization of HEWL with carboplatin without NaCl to eliminate the partial chemical conversion of carboplatin. Tetragonal HEWL crystals co-crystallized with carboplatin were successfully obtained in four different conditions, each at a different pH value. The structural results obtained show carboplatin bound to either one or both of the N atoms of His15 of HEWL, and this particular variation was dependent on the concentration of anions in the crystallization mixture and the elapsed time, as well as the pH used. The structural details of the bound carboplatin molecule also differed between them. Overall, the most detailed crystal structure showed the majority of the carboplatin atoms bound to the platinum centre; however, the four-carbon ring structure of the cyclobutanedicarboxylate moiety (CBDC) remained elusive. The potential impact of the results for the administration of carboplatin as an anticancer agent are described.

  18. Molecular Mechanisms of Pharmaceutical Drug Binding into Calsequestrin

    Directory of Open Access Journals (Sweden)

    ChulHee Kang

    2012-11-01

    Full Text Available Calsequestrin (CASQ is a major Ca2+-storage/buffer protein present in the sarcoplasmic reticulum of both skeletal (CASQ1 and cardiac (CASQ2 muscles. CASQ has significant affinity for a number of pharmaceutical drugs with known muscular toxicities. Our approach, with in silico molecular docking, single crystal X-ray diffraction, and isothermal titration calorimetry (ITC, identified three distinct binding pockets on the surface of CASQ2, which overlap with 2-methyl-2,4-pentanediol (MPD binding sites observed in the crystal structure. Those three receptor sites based on canine CASQ1 crystal structure gave a high correlation (R2 = 0.80 to our ITC data. Daunomycin, doxorubicin, thioridazine, and trifluoperazine showed strong affinity to the S1 site, which is a central cavity formed between three domains of CASQ2. Some of the moderate-affinity drugs and some high-affinity drugs like amlodipine and verapamil displayed their binding into S2 sites, which are the thioredoxin-like fold present in each CASQ domain. Docking predictions combined with dissociation constants imply that presence of large aromatic cores and less flexible functional groups determines the strength of binding affinity to CASQ. In addition, the predicted binding pockets for both caffeine and epigallocatechin overlapped with the S1 and S2 sites, suggesting competitive inhibition by these natural compounds as a plausible explanation for their antagonistic effects on cardiotoxic side effects.

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

    Directory of Open Access Journals (Sweden)

    Garima Tiwari

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

  20. Flexible moldable conductive current-limiting materials

    Science.gov (United States)

    Shea, John Joseph; Djordjevic, Miomir B.; Hanna, William Kingston

    2002-01-01

    A current limiting PTC device (10) has two electrodes (14) with a thin film of electric conducting polymer material (20) disposed between the electrodes, the polymer material (20) having superior flexibility and short circuit performance, where the polymer material contains short chain aliphatic diepoxide, conductive filler particles, curing agent, and, preferably, a minor amount of bisphenol A epoxy resin.

  1. Fast flexible electronics with strained silicon nanomembranes.

    Science.gov (United States)

    Zhou, Han; Seo, Jung-Hun; Paskiewicz, Deborah M; Zhu, Ye; Celler, George K; Voyles, Paul M; Zhou, Weidong; Lagally, Max G; Ma, Zhenqiang

    2013-01-01

    Fast flexible electronics operating at radio frequencies (>1 GHz) are more attractive than traditional flexible electronics because of their versatile capabilities, dramatic power savings when operating at reduced speed and broader spectrum of applications. Transferrable single-crystalline Si nanomembranes (SiNMs) are preferred to other materials for flexible electronics owing to their unique advantages. Further improvement of Si-based device speed implies significant technical and economic advantages. While the mobility of bulk Si can be enhanced using strain techniques, implementing these techniques into transferrable single-crystalline SiNMs has been challenging and not demonstrated. The past approach presents severe challenges to achieve effective doping and desired material topology. Here we demonstrate the combination of strained- NM-compatible doping techniques with self-sustained-strain sharing by applying a strain-sharing scheme between Si and SiGe multiple epitaxial layers, to create strained print-transferrable SiNMs. We demonstrate a new speed record of Si-based flexible electronics without using aggressively scaled critical device dimensions.

  2. Drag Coefficient of Thin Flexible Cylinder

    Science.gov (United States)

    Subramanian, Chelakara; Gurram, Harika

    2015-11-01

    Measurements of drag coefficients of thin flexible cylindrical wires are described for the Reynolds number range between 250 - 1000. Results indicate that the coefficient values are about 20 to 30 percent lower than the reported laminar flow values for rigid cylinders. Possible fluid dynamics mechanism causing the reduction in drag will be discussed.

  3. Modeling protein flexibility by distance geometry

    OpenAIRE

    Le Boudic-Jamin, Mathilde; Mucherino, Antonio; Andonov, Rumen

    2012-01-01

    National audience This long abstract discusses a strategy for modeling protein flexibility which is based on the discretization of the space of possible molecular conformations for a protein. The same discretization process was previously employed for discretizing Molecular Distance Geometry Problems (MDGPs).

  4. Flexible frontiers for text division into rows

    Directory of Open Access Journals (Sweden)

    Dan L. Lacrămă

    2009-01-01

    Full Text Available This paper presents an original solution for flexible hand-written text division into rows. Unlike the standard procedure, the proposed method avoids the isolated characters extensions amputation and reduces the recognition error rate in the final stage.

  5. Unlock the Rigidity and Design for Flexibility

    Science.gov (United States)

    Spante, Maria; Ericsson, Thommy; Sunnerstam, Maria; Huang-DeVoss, Cammy; Axelsson, Michael

    2010-01-01

    This paper reports findings from a project implementing the VL (virtual labs) site featuring flash-based animations developed at Stanford University. The main conclusion in this paper stresses the need to design for flexibility and adaptability of interactive media to better suit the specific situation teachers encounter in their everyday work, in…

  6. Prevention of pulsations caused by flexible risers

    NARCIS (Netherlands)

    Belfroid S.P.C; Golliard, J.; Korst, H.J.C.

    2013-01-01

    In the last few decades, flexible risers have increasingly been used in the offshore oil and gas industry. In gas applications these risers can generate high amplitude tonal pressure fluctuations when the gas velocity reaches a threshold value. The resulting pressure fluctuations can then cause high

  7. RMB Reform: Flexible, Yet True to Form

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Signs of a stable recovery are becoming more noticeable in China, especially after the People’s Bank of China, the central bank, decided to proceed with efforts to reform the renminbi (yuan) exchange rate regime and improve the currency’s flexibility.

  8. Flexible device for vertebral body replacement.

    Science.gov (United States)

    Main, J A; Wells, M E; Spengler, D M; Strauss, A M; Keller, T S

    1989-03-01

    A novel vertebral prosthesis is presented. The prosthesis was developed for surgical procedures requiring the resection of a complete vertebral body and the adjacent intervertebral discs, the design objective being to develop a flexible implant that would be robust enough to withstand the in vivo stress environment of the human spine. In theory, a flexible implant should preserve a more normal range of motion and apply less stress to surrounding tissue than a rigid implant. A prototype implant was constructed so as to combine a rigid stainless steel structure with flexible silicon rubber elements in order to form an implant with static and dynamic mechanical characteristics similar to those of the anterior spinal column. Implant flexibility characteristics were determined from ex vivo stress-strain behaviour during bending and compressive creep testing. Results from the bending tests indicated good agreement for the lateral and sagittal bending characteristics in comparison with in vitro bending tests of human lumbar motion segments. Comparison of the implant compressive creep response with similar in vitro tests on human lumbar intervertebral discs also demonstrated similarities in the time-dependent mechanical parameters. PMID:2704210

  9. Flexible Sensor Network Reprogramming for Logistics

    NARCIS (Netherlands)

    Evers, L.; Havinga, P.J.M.; Kuper, J.

    2007-01-01

    Besides the currently realized applications, Wireless Sensor Networks can be put to use in logistics processes. However, doing so requires a level of flexibility and safety not provided by the current WSN software platforms. This paper discusses a logistics scenario, and presents SensorScheme, a run

  10. Flexible, Mastery-Oriented Astrophysics Sequence.

    Science.gov (United States)

    Zeilik, Michael, II

    1981-01-01

    Describes the implementation and impact of a two-semester mastery-oriented astrophysics sequence for upper-level physics/astrophysics majors designed to handle flexibly a wide range of student backgrounds. A Personalized System of Instruction (PSI) format was used fostering frequent student-instructor interaction and role-modeling behavior in…

  11. A Model for Flexibly Editing CSCL Scripts

    Science.gov (United States)

    Sobreira, Pericles; Tchounikine, Pierre

    2012-01-01

    This article presents a model whose primary concern and design rationale is to offer users (teachers) with basic ICT skills an intuitive, easy, and flexible way of editing scripts. The proposal is based on relating an end-user representation as a table and a machine model as a tree. The table-tree model introduces structural expressiveness and…

  12. Enabling flexible processes by ECA orchestration architecture

    NARCIS (Netherlands)

    Gong, Y.; Janssen, M.; Overbeek, S.J.; Zuurmond, A.

    2009-01-01

    Governments are looking for ways to change their business processes rapidly to adapt to the ever-changing legislation, customer needs, and other changes in the environment. In recent years, the need for more flexibility has become eminent due to the long implementation times of new legislations. As

  13. Increases in rewards promote flexible behavior.

    Science.gov (United States)

    Shen, Y Jeremy; Chun, Marvin M

    2011-04-01

    Offering reward for performance can motivate people to perform a task better, but better preparation for one task usually means decreased flexibility to perform different tasks. In six experiments in which reward varied between low and high levels, we found that reward can encourage people to prepare more flexibly for different tasks, but only as it increased from the level on the previous trial. When the same high rewards were offered continuously trial after trial, people were more inclined to simply stick with doing what had worked previously. We demonstrated such enhancements in flexibility in task switching, a difficult visual search task, and an easier priming of pop-out search task, which shows that this effect generalizes from executive tasks to perceptual processes that require relatively little executive control. These findings suggest that relative, transient changes in reward can exert more potent effects on behavioral flexibility than can the absolute amount of reward, whether it consists of money or points in a social competition.

  14. Workplace Flexibility: From Research to Action

    Science.gov (United States)

    Galinsky, Ellen; Sakai, Kelly; Wigton, Tyler

    2011-01-01

    Ellen Galinsky, Kelly Sakai, and Tyler Wigton explore the "time famine" among American workers--the continuing sense among employees of not having enough time to manage the multiple responsibilities of work and personal and family life. Noting that large shares of U.S. employees report feeling the need for greater workplace flexibility to enable…

  15. IEA EBC Annex 67 Energy Flexible Buildings

    DEFF Research Database (Denmark)

    Marszal, Anna Joanna; Jensen, Søren Østergaard

    2016-01-01

    The foreseen large deployment of renewable energy sources may seriously affect the stability of energy grids. It will be necessary to control energy consumption to match instantaneous energy production. The built-in Energy Flexibility in buildings may be utilized for stabilizing the energy grids,...

  16. Flexible Ligand Docking Using Differential Evolution

    DEFF Research Database (Denmark)

    Thomsen, René

    2003-01-01

    the most favorable energetic conformation among the large space of possible protein-ligand complexes. Stochastic search methods, such as evolutionary algorithms (EAs), can be used to sample large search spaces effectively and is one of the preferred methods for flexible ligand docking. The differential...

  17. System Reduction and Damping of Flexible Structures

    DEFF Research Database (Denmark)

    Høgsberg, Jan Riess; Krenk, Steen

    2007-01-01

    An increasing number of flexible structures such as cable-stayed bridges, pedestrian bridges and high-rise buildings are fitted with local dampers to mitigate vibration problems. In principle the effect of local dampers can be analyzed by use of complex modes, e.g. in conjunction with an averaging...

  18. Flexible spin-orbit torque devices

    Energy Technology Data Exchange (ETDEWEB)

    Lee, OukJae; You, Long; Jang, Jaewon; Subramanian, Vivek [Department of Electrical Engineering and Computer Sciences, University of California at Berkeley, Berkeley, California 94720 (United States); Salahuddin, Sayeef [Department of Electrical Engineering and Computer Sciences, University of California at Berkeley, Berkeley, California 94720 (United States); Materials Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720 (United States)

    2015-12-21

    We report on state-of-the-art spintronic devices synthesized and fabricated directly on a flexible organic substrate. Large perpendicular magnetic anisotropy was achieved in ultrathin ferromagnetic heterostructures of Pt/Co/MgO sputtered on a non-rigid plastic substrate at room temperature. Subsequently, a full magnetic reversal of the Co was observed by exploiting the spin orbit coupling in Pt that leads to a spin accumulation at the Pt/Co interface when an in-plane current is applied. Quasi-static measurements show the potential for operating these devices at nano-second speeds. Importantly, the behavior of the devices remained unchanged under varying bending conditions (up to a bending radius of ≈ ±20–30 mm). Furthermore, the devices showed robust operation even after application of 10{sup 6} successive pulses, which is likely sufficient for many flexible applications. Thus, this work demonstrates the potential for integrating high performance spintronic devices on flexible substrates, which could lead to many applications ranging from flexible non-volatile magnetic memory to local magnetic resonance imaging.

  19. Computer program for flexible rotor dynamics analysis

    Science.gov (United States)

    Shen, F. A.

    1974-01-01

    Program analyzes general nonaxisymmetric and nonsynchronous transient and steady-state rotor dynamic performance of bending- and shear-wise flexible rotor-bearing system under various operating conditions. Program can be used as analytical study tool for general transient spin-speed and/or non-axisymmetric rotor motion.

  20. FAME - A Flexible Appearance Modelling Environment

    DEFF Research Database (Denmark)

    Stegmann, Mikkel Bille; Ersbøll, Bjarne Kjær; Larsen, Rasmus

    2003-01-01

    applications within medicine and describes a public domain implementation, namely the Flexible Appearance Modelling Environment (FAME). We give guidelines for the use of this research platform, and show that the optimisation techniques used renders it applicable to interactive medical applications. To increase...

  1. Flexible shielding system for radiation protection

    Science.gov (United States)

    Babin, A.

    1972-01-01

    Modular construction of low cost flexible radiation shielding panels consists of water filled steels cans, zinc bromide windows, turntable unit, master-slave manipulators, and interlocking lead bricks. Easy modifications of shielding wall thicknesses are obtained by rearranging overall geometry of portable components.

  2. Flexibility through Online Learning. At a Glance.

    Science.gov (United States)

    National Centre for Vocational Education Research, Leabrook (Australia).

    Research funded by the Flexible Learning Advisory Group during 2000-2002 on issues related to online learning and delivery in vocational education and training in Australia was consolidated. Key findings included the following: (1) most students who experienced online learning did so in a conventional class, using face-to-face and other strategies…

  3. On Quantification of Flexibility in Power Systems

    DEFF Research Database (Denmark)

    Bucher, Matthias A.; Delikaraoglou, Stefanos; Heussen, Kai;

    2015-01-01

    reasonable cost. In this paper, locational flexibility is defined anda unified framework to compare it against forecast uncertaintyis introduced. Both metrics are expressed in terms of rampingrate, power and energy and consider the network constraints.This framework is integrated into the operational...

  4. Can counter-stereotypes boost flexible thinking?

    NARCIS (Netherlands)

    M.A. Goclowska; R.J. Crisp; K. Labuschagne

    2012-01-01

    To reduce prejudice psychologists design interventions requiring people to think of counter-stereotypes (i.e., people who defy stereotypic expectations—a strong woman, a Black President). Grounded in the idea that stereotypes constrain the ability to think flexibly, we propose that thinking of count

  5. Flexible Twin Open Ring Metro WDM Network

    Institute of Scientific and Technical Information of China (English)

    Susumu Kinoshita; Cechan Tian; Satoru Ohdate; Koji Takeguchi; Yasuhiko Aoki

    2003-01-01

    We have demonstrated a flexible twin open ring WDM network for metro applications. A pair of optical switches in the network keeps the fiber rings open to prevent signal circulation. Traffics are broadcast to every node and selected at the receiving side. Superior transmission and protection switching are proved.

  6. Flexible Hybrid Organic-Inorganic Perovskite Memory.

    Science.gov (United States)

    Gu, Chungwan; Lee, Jang-Sik

    2016-05-24

    Active research has been done on hybrid organic-inorganic perovskite materials for application to solar cells with high power conversion efficiency. However, this material often shows hysteresis, which is undesirable, shift in the current-voltage curve. The hysteresis may come from formation of defects and their movement in perovskite materials. Here, we utilize the defects in perovskite materials to be used in memory operations. We demonstrate flexible nonvolatile memory devices based on hybrid organic-inorganic perovskite as the resistive switching layer on a plastic substrate. A uniform perovskite layer is formed on a transparent electrode-coated plastic substrate by solvent engineering. Flexible nonvolatile memory based on the perovskite layer shows reproducible and reliable memory characteristics in terms of program/erase operations, data retention, and endurance properties. The memory devices also show good mechanical flexibility. It is suggested that resistive switching is done by migration of vacancy defects and formation of conducting filaments under the electric field in the perovskite layer. It is believed that organic-inorganic perovskite materials have great potential to be used in high-performance, flexible memory devices. PMID:27093096

  7. II Conferencia internacional de pavimentos flexibles

    Directory of Open Access Journals (Sweden)

    Editorial, Equipo

    1968-02-01

    Full Text Available Not availableEn la semana del 7 al 12 de agosto pasado tuvo lugar en la Universidad de Ann Arbor, Estado de Michigan (EE. UU., la II Conferencia Internacional de Pavimentos Flexibles, dedicada especialmente a los métodos teóricos y experimentales de dimensionamiento y refuerzo de este tipo de pavimentos.

  8. Flexible hydrogel-based functional composite materials

    Science.gov (United States)

    Song, Jie; Saiz, Eduardo; Bertozzi, Carolyn R; Tomasia, Antoni P

    2013-10-08

    A composite having a flexible hydrogel polymer formed by mixing an organic phase with an inorganic composition, the organic phase selected from the group consisting of a hydrogel monomer, a crosslinker, a radical initiator, and/or a solvent. A polymerization mixture is formed and polymerized into a desired shape and size.

  9. Simulation of Flexible Objects in Robotics

    DEFF Research Database (Denmark)

    Fugl, Andreas Rune; Petersen, Henrik Gordon; Willatzen, Morten

    2012-01-01

    In this paper, we present what appears to be the first simulation model for grasping of flexible bodies based on the three-dimensional elastic constitutive relations and Newton's Second Law for solids known as the Navier-Cauchy equations. We give an overview of the most important equations for st...

  10. Flexible Structure of Peptide-Bound Filamin A Mechanosensor Domain Pair 20-21.

    Directory of Open Access Journals (Sweden)

    Jonne Seppälä

    Full Text Available Filamins (FLNs are large, multidomain actin cross-linking proteins with diverse functions. Besides regulating the actin cytoskeleton, they serve as important links between the extracellular matrix and the cytoskeleton by binding cell surface receptors, functioning as scaffolds for signaling proteins, and binding several other cytoskeletal proteins that regulate cell adhesion dynamics. Structurally, FLNs are formed of an amino terminal actin-binding domain followed by 24 immunoglobulin-like domains (IgFLNs. Recent studies have demonstrated that myosin-mediated contractile forces can reveal hidden protein binding sites in the domain pairs IgFLNa18-19 and 20-21, enabling FLNs to transduce mechanical signals in cells. The atomic structures of these mechanosensor domain pairs in the resting state are known, as well as the structures of individual IgFLN21 with ligand peptides. However, little experimental data is available on how interacting protein binding deforms the domain pair structures. Here, using small-angle x-ray scattering-based modelling, x-ray crystallography, and NMR, we show that the adaptor protein migfilin-derived peptide-bound structure of IgFLNa20-21 is flexible and adopts distinctive conformations depending on the presence or absence of the interacting peptide. The conformational changes reported here may be common for all peptides and may play a role in the mechanosensor function of the site.

  11. Motion and flexibility in human cytochrome p450 aromatase.

    Directory of Open Access Journals (Sweden)

    Wenhua Jiang

    Full Text Available The crystal structures of human placental aromatase in complex with the substrate androstenedione and exemestane have revealed an androgen-specific active site and the structural basis for higher order organization. However, X-ray structures do not provide accounts of movements due to short-range fluctuations, ligand binding and protein-protein association. In this work, we conduct normal mode analysis (NMA revealing the intrinsic fluctuations of aromatase, deduce the internal modes in membrane-free and membrane-integrated monomers as well as the intermolecular modes in oligomers, and propose a quaternary organization for the endoplasmic reticulum (ER membrane integration. Dynamics of the crystallographic oligomers from NMA is found to be in agreement with the isotropic thermal factors from the X-ray analysis. Calculations of the root mean square fluctuations of the C-alpha atoms from their equilibrium positions confirm that the rigid-core structure of aromatase is intrinsic regardless of the changes in steroid binding interactions, and that aromatase self-association does not deteriorate the rigidity of the catalytic cleft. Furthermore, NMA on membrane-integrated aromatase shows that the internal modes in all likelihood contribute to breathing of the active site access channel. The collective intermolecular hinge bending and twisting modes provide the flexibility in the quaternary association necessary for membrane integration of the aromatase oligomers. Taken together, fluctuations of the active site, the access channel, and the heme-proximal cavity, and a dynamic quaternary organization could all be essential components of the functional aromatase in its role as an ER membrane-embedded steroidogenic enzyme.

  12. Structure of the plasminogen kringle 4 binding calcium-free form of the C-type lectin-like domain of tetranectin

    DEFF Research Database (Denmark)

    Nielbo, Steen; Thomsen, Jens K; Graversen, Jonas Heilskov;

    2004-01-01

    Tetranectin is a homotrimeric protein containing a C-type lectin-like domain. This domain (TN3) can bind calcium, but in the absence of calcium, the domain binds a number of kringle-type protein ligands. Two of the calcium-coordinating residues are also critical for binding plasminogen kringle 4 (K...... no such flexibility is observed in holoTN3. In the 20 best nuclear magnetic resonance structures of apoTN3, the residues critical for K4 binding span a large conformational space. Together with the relaxation data, this indicates that the K4-ligand-binding site in apoTN3 is not preformed....

  13. Examination of the flexibility paradox in a Lean system

    OpenAIRE

    Osterman, Christer; Svensson Harari, Natalia; Lundin, Anders

    2014-01-01

    This paper explores if Lean is to be considered flexible or not. A multiple case study in the automotive industry is conducted to find the dependencies between Lean and flexibility. Since many definitions of flexibility and Lean exists, a pragmatic approach is sought where each cases own definition of Lean is used to analyze if the factors that enable flexibility are to be considered Lean or not. The context of this paper is volume and product flexibility. Lean and flexibility are found to be...

  14. Structures of mesophilic and extremophilic citrate synthases reveal rigidity and flexibility for function.

    Science.gov (United States)

    Wells, Stephen A; Crennell, Susan J; Danson, Michael J

    2014-10-01

    Citrate synthase (CS) catalyses the entry of carbon into the citric acid cycle and is highly-conserved structurally across the tree of life. Crystal structures of dimeric CSs are known in both "open" and "closed" forms, which differ by a substantial domain motion that closes the substrate-binding clefts. We explore both the static rigidity and the dynamic flexibility of CS structures from mesophilic and extremophilic organisms from all three evolutionary domains. The computational expense of this wide-ranging exploration is kept to a minimum by the use of rigidity analysis and rapid all-atom simulations of flexible motion, combining geometric simulation and elastic network modeling. CS structures from thermophiles display increased structural rigidity compared with the mesophilic enzyme. A CS structure from a psychrophile, stabilized by strong ionic interactions, appears to display likewise increased rigidity in conventional rigidity analysis; however, a novel modified analysis, taking into account the weakening of the hydrophobic effect at low temperatures, shows a more appropriate decreased rigidity. These rigidity variations do not, however, affect the character of the flexible dynamics, which are well conserved across all the structures studied. Simulation trajectories not only duplicate the crystallographically observed symmetric open-to-closed transitions, but also identify motions describing a previously unidentified antisymmetric functional motion. This antisymmetric motion would not be directly observed in crystallography but is revealed as an intrinsic property of the CS structure by modeling of flexible motion. This suggests that the functional motion closing the binding clefts in CS may be independent rather than symmetric and cooperative.

  15. Analytic QCD Binding Potentials

    CERN Document Server

    Fried, H M; Grandou, T; Sheu, Y -M

    2011-01-01

    This paper applies the analytic forms of a recent non-perturbative, manifestly gauge- and Lorentz-invariant description (of the exchange of all possible virtual gluons between quarks ($Q$) and/or anti-quarks ($\\bar{Q}$) in a quenched, eikonal approximation) to extract analytic forms for the binding potentials generating a model $Q$-$\\bar{Q}$ "pion", and a model $QQQ$ "nucleon". Other, more complicated $Q$, $\\bar{Q}$ contributions to such color-singlet states may also be identified analytically. An elementary minimization technique, relevant to the ground states of such bound systems, is adopted to approximate the solutions to a more proper, but far more complicated Schroedinger/Dirac equation; the existence of possible contributions to the pion and nucleon masses due to spin, angular momentum, and "deformation" degrees of freedom is noted but not pursued. Neglecting electromagnetic and weak interactions, this analysis illustrates how the one new parameter making its appearance in this exact, realistic formali...

  16. Binding of an Oligomeric Ellagitannin Series to Bovine Serum Albumin (BSA): Analysis by Isothermal Titration Calorimetry (ITC).

    Science.gov (United States)

    Karonen, Maarit; Oraviita, Marianne; Mueller-Harvey, Irene; Salminen, Juha-Pekka; Green, Rebecca J

    2015-12-16

    A unique series of oligomeric ellagitannins was used to study their interactions with bovine serum albumin (BSA) by isothermal titration calorimetry. Oligomeric ellagitannins, ranging from monomer to heptamer and a mixture of octamer-undecamers, were isolated as individual pure compounds. This series allowed studying the effects of oligomer size and other structural features. The monomeric to trimeric ellagitannins deviated most from the overall trends. The interactions of ellagitannin oligomers from tetramers to octa-undecamers with BSA revealed strong similarities. In contrast to the equilibrium binding constant, enthalpy showed an increasing trend from the dimer to larger oligomers. It is likely that first the macrocyclic part of the ellagitannin binds to the defined binding sites on the protein surface and then the "flexible tail" of the ellagitannin coats the protein surface. The results highlight the importance of molecular flexibility to maximize binding between the ellagitannin and protein surfaces.

  17. The genome landscape of ER{alpha}- and ER{beta}-binding DNA regions

    DEFF Research Database (Denmark)

    Liu, Yawen; Gao, Hui; Marstrand, Troels Torben;

    2008-01-01

    also regions that are bound by ERalpha only in the presence of ERbeta, as well as regions that are selectively bound by either receptor. Analysis of bound regions shows that regions bound by ERalpha have distinct properties in terms of genome landscape, sequence features, and conservation compared with......-bound regions having a predominance of classical estrogen response elements (EREs) and GC-rich motifs. Differences in the properties of ER bound regions might explain some of the differences in gene expression programs and physiological effects shown by the respective estrogen receptors. Udgivelsesdato: 2008...

  18. ENTHALPY-ENTROPY COMPENSATION AND COOPERATIVITY AS THERMODYNAMIC EPIPHENOMENA OF STRUCTURAL FLEXIBILITY IN LIGAND-RECEPTOR INTERACTIONS

    OpenAIRE

    Ferrante, Andrea; Gorski, Jack

    2012-01-01

    Ligand binding is a thermodynamically cooperative process in many biochemical systems characterized by the conformational flexibility of the reactants. However the contribution of conformational entropy to cooperativity of ligation needs to be elucidated. Here we perform kinetic and thermodynamic analyses on a panel of cycle-mutated peptides, derived from influenza H3 HA306-319, interacting with wild type and a mutant HLA-DR. We observe that within a certain range of peptide affinity, this sy...

  19. Water molecule network and active site flexibility of apo protein tyrosine phosphatase 1B

    DEFF Research Database (Denmark)

    Pedersen, A.K.; Peters, Günther H.J.; Møller, K.B.;

    2004-01-01

    Protein tyrosine phosphatase 1B (PTP1B) plays a key role as a negative regulator of insulin and leptin signalling and is therefore considered to be an important molecular target for the treatment of type 2 diabetes and obesity. Detailed structural information about the structure of PTP1B, including...... the conformation and flexibility of active-site residues as well as the water-molecule network, is a key issue in understanding ligand binding and enzyme kinetics and in structure-based drug design. A 1.95 Angstrom apo PTP1B structure has been obtained, showing four highly coordinated water molecules...

  20. Functional connectivity supporting the selective maintenance of feature-location binding in visual working memory

    Directory of Open Access Journals (Sweden)

    Sachiko eTakahama

    2014-06-01

    Full Text Available Information on an object’s features bound to its location is very important for maintaining object representations in visual working memory. Interactions with dynamic multi-dimensional objects in an external environment require complex cognitive control, including the selective maintenance of feature-location binding. Here, we used event-related functional magnetic resonance imaging to investigate brain activity and functional connectivity related to the maintenance of complex feature-location binding. Participants were required to detect task-relevant changes in feature-location binding between objects defined by color, orientation, and location. We compared a complex binding task requiring complex feature-location binding (color-orientation-location with a simple binding task in which simple feature-location binding, such as color-location, was task-relevant and the other feature was task-irrelevant. Univariate analyses showed that the dorsolateral prefrontal cortex (DLPFC, hippocampus, and frontoparietal network were activated during the maintenance of complex feature-location binding. Functional connectivity analyses indicated cooperation between the inferior precentral sulcus (infPreCS, DLPFC, and hippocampus during the maintenance of complex feature-location binding. In contrast, the connectivity for the spatial updating of simple feature-location binding determined by reanalyzing the data from Takahama et al. (2010 demonstrated that the superior parietal lobule (SPL cooperated with the DLPFC and hippocampus. These results suggest that the connectivity for complex feature-location binding does not simply reflect general memory load and that the DLPFC and hippocampus flexibly modulate the dorsal frontoparietal network, depending on the task requirements, with the infPreCS involved in the maintenance of complex feature-location binding and the SPL involved in the spatial updating of simple feature-location binding.

  1. Functional connectivity supporting the selective maintenance of feature-location binding in visual working memory.

    Science.gov (United States)

    Takahama, Sachiko; Saiki, Jun

    2014-01-01

    Information on an object's features bound to its location is very important for maintaining object representations in visual working memory. Interactions with dynamic multi-dimensional objects in an external environment require complex cognitive control, including the selective maintenance of feature-location binding. Here, we used event-related functional magnetic resonance imaging to investigate brain activity and functional connectivity related to the maintenance of complex feature-location binding. Participants were required to detect task-relevant changes in feature-location binding between objects defined by color, orientation, and location. We compared a complex binding task requiring complex feature-location binding (color-orientation-location) with a simple binding task in which simple feature-location binding, such as color-location, was task-relevant and the other feature was task-irrelevant. Univariate analyses showed that the dorsolateral prefrontal cortex (DLPFC), hippocampus, and frontoparietal network were activated during the maintenance of complex feature-location binding. Functional connectivity analyses indicated cooperation between the inferior precentral sulcus (infPreCS), DLPFC, and hippocampus during the maintenance of complex feature-location binding. In contrast, the connectivity for the spatial updating of simple feature-location binding determined by reanalyzing the data from Takahama et al. (2010) demonstrated that the superior parietal lobule (SPL) cooperated with the DLPFC and hippocampus. These results suggest that the connectivity for complex feature-location binding does not simply reflect general memory load and that the DLPFC and hippocampus flexibly modulate the dorsal frontoparietal network, depending on the task requirements, with the infPreCS involved in the maintenance of complex feature-location binding and the SPL involved in the spatial updating of simple feature-location binding. PMID:24917833

  2. Polyaniline modified flexible conducting paper for cancer detection

    Science.gov (United States)

    Kumar, Saurabh; Sen, Anindita; Kumar, Suveen; Augustine, Shine; Yadav, Birendra K.; Mishra, Sandeep; Malhotra, Bansi D.

    2016-05-01

    We report results of studies relating to the fabrication of a flexible, disposable, and label free biosensing platform for detection of the cancer biomarker (carcinoembryonic antigen, CEA). Polyaniline (PANI) has been electrochemically deposited over gold sputtered paper (Au@paper) for covalent immobilization of monoclonal carcinoembryonic antibodies (anti-CEA). The bovine serum albumin (BSA) has been used for blocking nonspecific binding sites at the anti-CEA conjugated PANI/Au@Paper. The PANI/Au@Paper, anti-CEA/PANI/Au@Paper, and BSA/anti-CEA/PANI/Au@Paper platforms have been characterized using scanning electron microscopy, X-ray diffraction, Fourier transmission infrared spectroscopy, chronoamperometry, and electrochemical impedance techniques. The results of the electrochemical response studies indicate that this BSA/anti-CEA/PANI/Au@paper electrode has sensitivity of 13.9 μA ng-1 ml cm2, shelf life of 22 days, and can be used to estimate CEA in the range of 2-20 ng ml-1. This paper sensor has been validated by detection of CEA in serum samples of cancer patients via immunoassay technique.

  3. ATP-binding site of adenylate kinase: mechanistic implications of its homology with ras-encoded p21, F1-ATPase, and other nucleotide-binding proteins.

    Science.gov (United States)

    Fry, D C; Kuby, S A; Mildvan, A S

    1986-02-01

    The MgATP binding site of adenylate kinase, located by a combination of NMR and x-ray diffraction, is near three protein segments, five to seven amino acids in length, that are homologous in sequence to segments found in other nucleotide-binding phosphotransferases, such as myosin and F1-ATPase, ras p21 and transducin GTPases, and cAMP-dependent and src protein kinases, suggesting equivalent mechanistic roles of these segments in all of these proteins. Segment 1 is a glycine-rich flexible loop that, on adenylate kinase, may control access to the ATP-binding site by changing its conformation. Segment 2 is an alpha-helix containing two hydrophobic residues that interact with the adenine-ribose moiety of ATP, and a lysine that may bind to the beta- and gamma-phosphates of ATP. Segment 3 is a hydrophobic strand of parallel beta-pleated sheet, terminated by a carboxylate, that flanks the triphosphate binding site. The various reported mutations of ras p21 that convert it to a transforming agent all appear to involve segment 1, and such substitutions may alter the properties of p21 by hindering a conformational change at this segment. In F1-ATPase, the flexible loop may, by its position, control both the accessibility and the ATP/ADP equilibrium constant on the enzyme.

  4. Quarkonium Binding and Entropic Force

    CERN Document Server

    Satz, Helmut

    2015-01-01

    A Q-Qbar bound state represents a balance between repulsive kinetic and attractive potential energy. In a hot quark-gluon plasma, the interaction potential experiences medium effects. Color screening modifies the attractive binding force between the quarks, while the increase of entropy with Q-Qbar separation gives rise to a growing repulsion. We study the role of these phenomena for in-medium Q-Qbar binding and dissociation. It is found that the relevant potential for Q-Qbar binding is the free energy F; with increasing Q-Qbar separation, further binding through the internal energy U is compensated by repulsive entropic effects.

  5. Supporting Flexible Data Distribution in Software DSMs

    Institute of Scientific and Technical Information of China (English)

    洪锦伟; 陈国良; 张兆庆

    2000-01-01

    Page-based software DSM systems suffer from false sharing caused by the large sharing granularity, and only support one-dimension Block or Cyclic block data distribution schemes. Thus applications running on them will suffer from poor data locality and will be able to exploit parallelism only when using a large number of processors. In this paper, a way towards supporting flexible data distribu tion (FDD) on software DSM system is presented. Small granularity-tunable blocks, the size of which can be set by compiler or programmer, are used to overlap the working data sets distributed among processors. The FDD was implemented on a software DSM system called JIAJiA. Compared with Block/Cyclic-block distribution schemes used by most DSM systems now, experiments show that the proposed way of flexible data distribution is more effective. The performance of the applications used in the experiments is significantly improved.

  6. Flexible Software Process Lines in Practice

    DEFF Research Database (Denmark)

    Kuhrmann, Marco; Ternité, Thomas; Friedrich, Jan;

    2016-01-01

    and manage variable software processes, by combining pre-defined and standardized process assets that can be reused, modified, and extended using a well-defined customization approach. Hence, process engineers can ground context-specific process variants in a standardized or domain-specific reference model...... that can be adapted to the respective context. In this article, we present an approach to construct flexible software process lines and show its practical application in the German V-Modell XT. The presented approach emerges from a 10-year research endeavor and was used to enhance the metamodel of the V-Modell......Process flexibility and adaptability is a frequently discussed topic in literature, and several approaches propose techniques to improve and optimize software processes for a given organization- or project context. A software process line (SPrL) is an instrument to systematically construct...

  7. Flexible Skins Containing Integrated Sensors and Circuitry

    Science.gov (United States)

    Liu, Chang

    2007-01-01

    Artificial sensor skins modeled partly in imitation of biological sensor skins are undergoing development. These sensor skins comprise flexible polymer substrates that contain and/or support dense one- and two-dimensional arrays of microscopic sensors and associated microelectronic circuits. They afford multiple tactile sensing modalities for measuring physical phenomena that can include contact forces; hardnesses, temperatures, and thermal conductivities of objects with which they are in contact; and pressures, shear stresses, and flow velocities in fluids. The sensor skins are mechanically robust, and, because of their flexibility, they can be readily attached to curved and possibly moving and flexing surfaces of robots, wind-tunnel models, and other objects that one might seek to equip for tactile sensing. Because of the diversity of actual and potential sensor-skin design criteria and designs and the complexity of the fabrication processes needed to realize the designs, it is not possible to describe the sensor-skin concept in detail within this article.

  8. The motion of interconnected flexible bodies

    Science.gov (United States)

    Hopkins, A. S.

    1975-01-01

    The equations of motion for an arbitrarily interconnected collection of substructures are derived. The substructures are elastic bodies which may be idealized as finite element assemblies and are subject to small deformations relative to a nominal state. Interconnections between the elastic substructures permit large relative translations and rotations between substructures, governed by Pfaffian constraints describing the connections. Screw connections (permitting rotation about and translation along a single axis) eliminate constraint forces and incorporate modal coupling. The problem of flexible spacecraft simulation is discussed. Hurty's component mode approach is extended by permitting interconnected elastic substructures large motions relative to each other and relative to inertial space. The hybrid coordinate methods are generalized by permitting all substructures to be flexible (rather than only the terminal members of a topological tree of substructures). The basic relationships of continuum mechanics are developed.

  9. Procedural Optimization Models for Multiobjective Flexible JSSP

    Directory of Open Access Journals (Sweden)

    Elena Simona NICOARA

    2013-01-01

    Full Text Available The most challenging issues related to manufacturing efficiency occur if the jobs to be sched-uled are structurally different, if these jobs allow flexible routings on the equipments and mul-tiple objectives are required. This framework, called Multi-objective Flexible Job Shop Scheduling Problems (MOFJSSP, applicable to many real processes, has been less reported in the literature than the JSSP framework, which has been extensively formalized, modeled and analyzed from many perspectives. The MOFJSSP lie, as many other NP-hard problems, in a tedious place where the vast optimization theory meets the real world context. The paper brings to discussion the most optimization models suited to MOFJSSP and analyzes in detail the genetic algorithms and agent-based models as the most appropriate procedural models.

  10. MATERIAL HANDLING IN FLEXIBLE MANUFACTURING SYSTEM

    Directory of Open Access Journals (Sweden)

    Mr. Neeraj Dahiya

    2011-08-01

    Full Text Available The objective of this study is to analyze the system performanceof a flexible manufacturing system cell. The study givesinformation on production potential of the cell by groupingcommon parts. To complete this, computer simulation models aredeveloped using the SIMAN simulation language. Initially nomaterial handling is provided to the manufacturing system to getan upper bound estimate of production output. Next, we explorethe impact that an automatic guided vehicle (AGV has on systemperformance with manufacturing system. The final analysis isperformed in which a conveyor is implemented for the materialhandling. The performance result with comparison is presented inthe form of confidence intervals. After examine the simulationresults, we recommend to implement a conveyor system formaterial handling. Use of AGV in the flexible manufacturingsystem creates a bottleneck which causes a dramatically decreasein the production: as compare to a conveyor as the materialhandling system which does not limit the daily production outputof the manufacturing cell.

  11. Varying flexibilities in systems of organised decentralisation

    DEFF Research Database (Denmark)

    Ilsøe, Anna; Andersen, Søren Kaj

    to this paradox a qualitative study of working time regulation in the metal industry in Denmark and Germany was performed in the spring of 2005. In addition to five case studies of company-based agreements in Denmark and Germany (Baden-Württemberg) the study consisted of analysing statistical data, legislative...... the framework agreements on variable hours are specified, is more decentralised in Denmark and allows an adjustment of working time closer to the single employee. 2) Both in the German and Danish metal sectors company-based agreements regulate the growing use of flexible working hours. Though the trade union...... be while the response of the German system should rather be interpreted as a reactive organised decentralisation. 3) The varying regulation of working time flexibility in Germany and Denmark implies varying risks in the regulation. In Germany lacking competencies in small or medium-sized companies lead...

  12. Taming molecular flexibility to tackle rare diseases.

    Science.gov (United States)

    Cubellis, Maria Vittoria; Baaden, Marc; Andreotti, Giuseppina

    2015-06-01

    Many mutations responsible of Fabry disease destabilize lysosomal alpha-galactosidase, but retain the enzymatic activity. These mutations are associated to a milder phenotype and are potentially curable with a pharmacological therapy either with chaperones or with drugs that modulate proteostasis. We demonstrate the effectiveness of molecular dynamics simulations to correlate the genotype to the severity of the disease. We studied the relation between protein flexibility and residual enzymatic activity of pathological missense mutants in the cell. We found that mutations occurring at flexible sites are likely to retain activity in vivo. The usefulness of molecular dynamics for diagnostic purposes is not limited to lysosomal galactosidase because destabilizing mutations are widely encountered in other proteins, too, and represent a large share of all the ones associated to human diseases.

  13. Wave-induced dynamics of flexible blades

    CERN Document Server

    Luhar, M

    2015-01-01

    We present an experimental and numerical study that describes the motion of flexible blades, scaled to be dynamically similar to natural aquatic vegetation, forced by wave-induced oscillatory flows. For the conditions tested, blade motion is governed primarily by two dimensionless variables: (i) the Cauchy number, $Ca$, which represents the ratio of the hydrodynamic forcing to the restoring force due to blade stiffness, and (ii) the ratio of the blade length to the wave orbital excursion, $L$. For flexible blades with $Ca \\gg 1$, the relationship between drag and velocity can be described by two different scaling laws at the large- and small-excursion limits. For large excursions ($L \\ll 1$), the flow resembles a unidirectional current and the scaling laws developed for steady-flow reconfiguration studies hold. For small excursions ($L \\gg 1$), the beam equations may be linearized and a different scaling law for drag applies. The experimental force measurements suggest that the small-excursion scaling applies...

  14. Flexible Bit Preservation on a National Basis

    DEFF Research Database (Denmark)

    Jurik, Bolette; Nielsen, Anders Bo; Zierau, Eld

    2012-01-01

    In this paper we present the results from The Danish National Bit Repository project. The project aim was establishment of a system that can offer flexible and sustainable bit preservation solutions to Danish cultural heritage institutions. Here the bit preservation solutions must include support...... of bit safety as well as other requirements like e.g. confidentiality and availability. The Danish National Bit Repository is motivated by the need to investigate and handle bit preservation for digital cultural heritage. Digital preservation relies on the integrity of the bits which digital material...... consists of, and it is with this focus that the project was initiated. This paper summarizes the requirements for a general system to offer bit preservation to cultural heritage institutions. On this basis the paper describes the resulting flexible system which can support such requirements. The paper...

  15. Screen-printed flexible MRI receive coils

    Science.gov (United States)

    Corea, Joseph R.; Flynn, Anita M.; Lechêne, Balthazar; Scott, Greig; Reed, Galen D.; Shin, Peter J.; Lustig, Michael; Arias, Ana C.

    2016-03-01

    Magnetic resonance imaging is an inherently signal-to-noise-starved technique that limits the spatial resolution, diagnostic image quality and results in typically long acquisition times that are prone to motion artefacts. This limitation is exacerbated when receive coils have poor fit due to lack of flexibility or need for padding for patient comfort. Here, we report a new approach that uses printing for fabricating receive coils. Our approach enables highly flexible, extremely lightweight conforming devices. We show that these devices exhibit similar to higher signal-to-noise ratio than conventional ones, in clinical scenarios when coils could be displaced more than 18 mm away from the body. In addition, we provide detailed material properties and components performance analysis. Prototype arrays are incorporated within infant blankets for in vivo studies. This work presents the first fully functional, printed coils for 1.5- and 3-T clinical scanners.

  16. Computational Control of Flexible Aerospace Systems

    Science.gov (United States)

    Sharpe, Lonnie, Jr.; Shen, Ji Yao

    1994-01-01

    The main objective of this project is to establish a distributed parameter modeling technique for structural analysis, parameter estimation, vibration suppression and control synthesis of large flexible aerospace structures. This report concentrates on the research outputs produced in the last two years of the project. The main accomplishments can be summarized as follows. A new version of the PDEMOD Code had been completed. A theoretical investigation of the NASA MSFC two-dimensional ground-based manipulator facility by using distributed parameter modelling technique has been conducted. A new mathematical treatment for dynamic analysis and control of large flexible manipulator systems has been conceived, which may provide a embryonic form of a more sophisticated mathematical model for future modified versions of the PDEMOD Codes.

  17. Analysis of flexible structures under lateral impact

    Energy Technology Data Exchange (ETDEWEB)

    Ramirez, D. F. [Paul C. Kizzo and Associates Inc., Seismic Structural Group, Oakland, CA 94612 (United States); Razavi, H. [AREVA Inc., Civil Seismic Group, San Jose, CA 95119 (United States)

    2012-07-01

    Three methods for analysis of flexible structures under lateral impact are presented. The first proposed method (Method A) consists of: (1) modifying an available deceleration on a rigid target with conservation principles to account for structural flexibility; and (2) transient nonlinear analysis of the structure with the corrected forcing function. The second proposed method (Method B) is similar to Method A in obtaining the forcing function but it solves the equations of motion of an idealized two-degree-of-freedom system instead of directly using conservation principles. The last method simply provides the maximum force in the structure using the conservation of energy and linear momentum. A coupled simulation is also performed in LS-DYNA and compared against the proposed methods. A case study is presented to illustrate the applicability of all three methods and the LS-DYNA simulation. (authors)

  18. Variable structure motifs for transcription factor binding sites

    Directory of Open Access Journals (Sweden)

    Wernisch Lorenz

    2010-01-01

    Full Text Available Abstract Background Classically, models of DNA-transcription factor binding sites (TFBSs have been based on relatively few known instances and have treated them as sites of fixed length using position weight matrices (PWMs. Various extensions to this model have been proposed, most of which take account of dependencies between the bases in the binding sites. However, some transcription factors are known to exhibit some flexibility and bind to DNA in more than one possible physical configuration. In some cases this variation is known to affect the function of binding sites. With the increasing volume of ChIP-seq data available it is now possible to investigate models that incorporate this flexibility. Previous work on variable length models has been constrained by: a focus on specific zinc finger proteins in yeast using restrictive models; a reliance on hand-crafted models for just one transcription factor at a time; and a lack of evaluation on realistically sized data sets. Results We re-analysed binding sites from the TRANSFAC database and found motivating examples where our new variable length model provides a better fit. We analysed several ChIP-seq data sets with a novel motif search algorithm and compared the results to one of the best standard PWM finders and a recently developed alternative method for finding motifs of variable structure. All the methods performed comparably in held-out cross validation tests. Known motifs of variable structure were recovered for p53, Stat5a and Stat5b. In addition our method recovered a novel generalised version of an existing PWM for Sp1 that allows for variable length binding. This motif improved classification performance. Conclusions We have presented a new gapped PWM model for variable length DNA binding sites that is not too restrictive nor over-parameterised. Our comparison with existing tools shows that on average it does not have better predictive accuracy than existing methods. However, it does

  19. Becoming more systematic about flexible learning: beyond time and distance

    Directory of Open Access Journals (Sweden)

    Wim De Boer

    2005-12-01

    Full Text Available Changes in higher education frequently involve the need for more flexibility in course design and delivery. Flexibility is a concept that can be operationalized in many ways. One approach to conceptualizing flexibility within courses is to distinguish planning-type flexibility, which the instructor can designate before the course begins and which needs to be managed when the course is offered, for interpersonal flexibility, which relates more to the dynamics of the course as it is experienced by the learners. Course management systems (CMSs offer options that can support both of these sorts of flexibility, if instructors use the CMSs with a systematic frame of reference. The instructor faces challenges in managing both types of flexibility, but the experience at one institution shows that being systematic about flexibility choices and ways to support those choices in the institutional CMS can help in meeting these challenges.

  20. Behavioral flexibility and problem solving in an invasive bird.

    Science.gov (United States)

    Logan, Corina J

    2016-01-01

    Behavioral flexibility is considered an important trait for adapting to environmental change, but it is unclear what it is, how it works, and whether it is a problem solving ability. I investigated behavioral flexibility and problem solving experimentally in great-tailed grackles, an invasive bird species and thus a likely candidate for possessing behavioral flexibility. Grackles demonstrated behavioral flexibility in two contexts, the Aesop's Fable paradigm and a color association test. Contrary to predictions, behavioral flexibility did not correlate across contexts. Four out of 6 grackles exhibited efficient problem solving abilities, but problem solving efficiency did not appear to be directly linked with behavioral flexibility. Problem solving speed also did not significantly correlate with reversal learning scores, indicating that faster learners were not the most flexible. These results reveal how little we know about behavioral flexibility, and provide an immense opportunity for future research to explore how individuals and species can use behavior to react to changing environments.

  1. Flexible Manufacturing Systems: What's in It for the Manufacturer.

    Science.gov (United States)

    Chowdhury, A. R.; Peckman, Donald C.

    1987-01-01

    The authors define the Flexible Manufacturing System and outline its history. They describe what the processing time includes and provide advantages and disadvantages of Flexible Manufacturing Systems compared to conventional manufacturing. (CH)

  2. Transmission of Infection by Flexible Gastrointestinal Endoscopy and Bronchoscopy

    NARCIS (Netherlands)

    Kovaleva, Julia; Peters, Frans T. M.; van der Mei, Henny C.; Degener, John E.

    2013-01-01

    Flexible endoscopy is a widely used diagnostic and therapeutic procedure. Contaminated endoscopes are the medical devices frequently associated with outbreaks of health care-associated infections. Accurate reprocessing of flexible endoscopes involves cleaning and high-level disinfection followed by

  3. Irreversible Investment, Operating Flexibility, and Time Lags

    OpenAIRE

    Takashima, Ryuta; GOTO, MAKOTO; Tsujimura, Motoh

    2010-01-01

    We consider an optimal investment problem when a firm such as an electric power company has the operational flexibility to expand and contract capacity with fixed cost. This problem is formulated as an impulse control problem combined with optimal stopping. Consequently, we obtain optimal investment timing, optimal capacity expansion and contraction timing, and the investment value. We also show investment, capacity expansion and contraction rule are influenced by the price volatility and the...

  4. IRREVERSIBLE INVESTMENT, OPERATING FLEXIBILITY, AND TIME LAGS

    OpenAIRE

    RYUTA TAKASHIMA; MAKOTO GOTO; MOTOH TSUJIMURA

    2010-01-01

    We consider an optimal investment problem when a firm such as an electric power company has the operational flexibility to expand and contract capacity with fixed cost. This problem is formulated as an impulse control problem combined with optimal stopping. Consequently, we obtain optimal investment timing, optimal capacity expansion and contraction timing, and the investment value. We also show investment, capacity expansion and contraction rule are influenced by the price volatility and the...

  5. Multifunctional Weft-knitted Flexible Composite Structures

    OpenAIRE

    Ali, S.; Fernando, A.; Potluri, P.;Gresil, M.

    2015-01-01

    Multifunctional composite structures offer unique features such as the ability to sense and respond to external stimuli that can be force, pressure or temperature. Knitted preforms are popular due their excellent properties like flexibility and impact resistance. So far, most of the research is focused on mechanical properties of rigid knitted composites structures. In this research, a preform for a composite is produced having a knitted functional sensing layer constructed using stainless st...

  6. Flexible resources allocation techniques: characteristics and modelling

    OpenAIRE

    Attia, El-Awady; Edi, Kouassi Hilaire; Duquenne, Philippe

    2012-01-01

    International audience At the interface between engineering, economics, social sciences and humanities, industrial engineering aims to provide answers to various sectors of business problems. One of these problems is the adjustment between the workload needed by the work to be realised and the availability of the company resources. The objective of this work is to help to find a methodology for the allocation of flexible human resources in industrial activities planning and scheduling. Thi...

  7. Imposing Theoretical Regularity on Flexible Functional Forms

    OpenAIRE

    Apostolos Serletis; Guohua Feng

    2013-01-01

    In this paper we build on work by Gallant and Golub (1984), Diewert and Wales (1987), and Barnett (2002) and provide a comparison among three different methods of imposing theoretical regularity on flexible functional forms - reparameterization using Cholesky factorization, constrained optimization, and Bayesian methodology. We apply the methodology to a translog cost and share equation system and make a distinction between local, regional, pointwise, and global regularity. We find that the i...

  8. MATERIAL HANDLING IN FLEXIBLE MANUFACTURING SYSTEM

    OpenAIRE

    Mr. Neeraj Dahiya; Mr. Neeraj Nirmal

    2011-01-01

    The objective of this study is to analyze the system performanceof a flexible manufacturing system cell. The study givesinformation on production potential of the cell by groupingcommon parts. To complete this, computer simulation models aredeveloped using the SIMAN simulation language. Initially nomaterial handling is provided to the manufacturing system to getan upper bound estimate of production output. Next, we explorethe impact that an automatic guided vehicle (AGV) has on systemperforma...

  9. Flexible contracts and human capital investments

    OpenAIRE

    Fouarge, D.; Grip, A. de; Smits, W.; de Vries, M R

    2011-01-01

    As suggested by human capital theory, workers with flexible contracts participate lessoften in training than those with permanent contracts. We find that this is merely dueto the fact that flexworkers receive less employer–funded training, a gap they can onlypartly compensate for by their own training investments. Flexworkers particularlyparticipate less in firm–specific training that is meant to keep up with new skilldemands than workers with permanent contracts. However, for those who parti...

  10. Flexible work and immigration in Europe

    OpenAIRE

    Raess, D.; Burgoon, B.

    2013-01-01

    Immigration has risen substantially in many European economies, with far-reaching if still uncertain implications for labour markets and industrial relations. This article investigates such implications, focusing on employment flexibility, involving both ‘external flexibility’ (fixed-term or temporary agency and/or involuntary part-time work) and ‘internal flexibility’ (overtime and/or balancing-time accounts). The article identifies reasons why immigration should generally increase the incid...

  11. Capacity of Deep Water Flexible Risers

    OpenAIRE

    Thorsen, Mats Jørgen

    2011-01-01

    A flexible riser operating in deep water will experience large environmental forces. Due to the length of the riser, dynamic tension from drag forces will be substantial. The tensile force is transferred directly into the end fitting, and fatigue damage may be critical at this point. In addition, the large hydrostatic pressure at the ocean floor may induce compressive stresses in the tensile armor, something this component is not designed for. In connection with these challenges, this thesis ...

  12. Flexible and scalable digital library search

    OpenAIRE

    Windhouwer, M.A.; A. R. Schmidt; Zwol, van, Roelof; Petkovic, M; Blok, H.E.

    2001-01-01

    In this report the development of a specialised search engine for a digital library is described. The proposed system architecture consists of three levels: the conceptual, the logical and the physical level. The conceptual level schema enables by its exposure of a domain specific schema semantically rich conceptual search. The logical level provides a description language to achieve a high degree of flexibility for multimedia retrieval. The physical level takes care of scalable and efficient...

  13. Calculation Methodology for Flexible Arithmetic Processing

    OpenAIRE

    García Chamizo, Juan Manuel; Mora Pascual, Jerónimo Manuel; Mora Mora, Higinio; Signes Pont, María Teresa

    2003-01-01

    A new operation model of flexible calculation that allows us to adjust the operation delay depending on the available time is presented. The operation method design uses look-up tables and progressive construction of the result. The increase in the operators’ granularity opens up new possibilities in calculation methods and microprocessor design. This methodology, together with the advances in technology, enables the functions of an arithmetic unit to be implemented on the basis of techniques...

  14. Time-Precision Flexible Arithmetic Unit

    OpenAIRE

    García Chamizo, Juan Manuel; Mora Pascual, Jerónimo Manuel; Mora Mora, Higinio; Signes Pont, María Teresa

    2003-01-01

    A new conception of flexible calculation that allows us to adjust an operation depending on the available time computation is presented. The proposed arithmetic unit is based on this principle. It contains a control operation module that determines the process time of each calculation. The operation method design uses precalculated data stored in look-up tables, which provide, above all, quality results and systematization in the implementation of low level primitives that set parameters for ...

  15. Microstrips Ladder Assembly using Flexible Microcables.

    CERN Document Server

    Borshchov, V N; CERN. Geneva; Kiprich, S; Maslov, N I; Prokhorets, I; Reznik, A; Runólfsson, O; Ruzhitskaya, L; Starkov, V

    1995-01-01

    The flexible microcables are studied to evaluate the possibility of their application as an interconnection for both microstrips module and ladder of the ALICE detector. We managed to produce the microcables and to bond them directly to detector connection pads without any wire bonding. It permits for read-out chips to be displaced to one of sides of the double-sided microstrip detector.

  16. Simulating charge transport in flexible systems

    OpenAIRE

    Timothy Clark

    2015-01-01

    Systems in which movements occur on two significantly different time domains, such as organic electronic components with flexible molecules, require different simulation techniques for the two time scales. In the case of molecular electronics, charge transport is complicated by the several different mechanisms (and theoretical models) that apply in different cases. We cannot yet combine time scales of molecular and electronic movement in simulations of real systems. This review describes our ...

  17. Flexible Tactile Sensor Using Polyurethane Thin Film

    OpenAIRE

    Seiji Aoyagi; Tomokazu Takahashi; Masato Suzuki

    2012-01-01

    A novel capacitive tactile sensor using a polyurethane thin film is proposed in this paper. In previous studies, capacitive tactile sensors generally had an air gap between two electrodes in order to enhance the sensitivity. In this study, there is only polyurethane thin film and no air gap between the electrodes. The sensitivity of this sensor is higher than the previous capacitive tactile sensors because the polyurethane is a fairly flexible elastomer and the film is very thin (about 1 µm)....

  18. A More Flexible Lipoprotein Sorting Pathway

    OpenAIRE

    Chahales, Peter; Thanassi, David G.

    2015-01-01

    Lipoprotein biogenesis in Gram-negative bacteria occurs by a conserved pathway, each step of which is considered essential. In contrast to this model, LoVullo and colleagues demonstrate that the N-acyl transferase Lnt is not required in Francisella tularensis or Neisseria gonorrhoeae. This suggests the existence of a more flexible lipoprotein pathway, likely due to a modified Lol transporter complex, and raises the possibility that pathogens may regulate lipoprotein processing to modulate int...

  19. Six principles to enhance health workforce flexibility

    OpenAIRE

    Nancarrow, Susan A

    2015-01-01

    Abstract This paper proposes approaches to break down the boundaries that reduce the ability of the health workforce to respond to population needs, or workforce flexibility. Accessible health services require sufficient numbers and types of skilled workers to meet population needs. However, there are several reasons that the health workforce cannot or does not meet population needs. These primarily stem from workforce shortages. However, the health workforce can also be prevented from respon...

  20. FAME - A Flexible Appearance Modelling Environment

    OpenAIRE

    Stegmann, Mikkel Bille; Ersbøll, Bjarne Kjær; Larsen, Rasmus

    2003-01-01

    Combined modelling of pixel intensities and shape has proven to be a very robust and widely applicable approach to interpret images. As such the Active Appearance Model (AAM) framework has been applied to a wide variety of problems within medical image analysis. This paper summarises AAM applications within medicine and describes a public domain implementation, namely the Flexible Appearance Modelling Environment (FAME). We give guidelines for the use of this research platform, and show that ...

  1. CONCEPT OF ADVANCED FLEXIBLE USE OF AIRSPACE

    Directory of Open Access Journals (Sweden)

    Oleksandr Luppo

    2016-06-01

    Full Text Available Purpose: Concept of Flexible Use of Airspace (FUA allows to eliminate many problems on the basis of civil-military coordination, but there are still a lot of areas for improvement. These improvements will be implemented in the Advanced Flexible Use of Airspace (AFUA concept. Methods: We examine the airspace structure in the frames of AFUA concept, which includes variable profile areas, temporary reserved and temporary segregated areas, danger or restricted areas. Mission Trajectory in AFUA which allows designing ad-hoc structures delineation at short notice is also examined. Regarding the performance enhancements of AFUA we compare these with FUA concept. Examination of AFUA structure gives us better view of the functions and opportunities of this concept. Result: AFUA concept provides many advantages for the civil aviation stakeholders and includes many other positive sides. Variable Profile Areas provide more flexibility, particularly in a high density traffic area and any combination of basic volume possible. Collaborative decision-making will increase the situational awareness of both parties and help to decrease the transit between airbases and training areas, allows military to use larger airspaces for missions on an absolute time-limited basis. As a result of mission trajectory implementation in AFUA concept general air traffic crossing are possible in all type of airspace structures, after coordination or under specific permanent agreements. The use of Centralized AFUA Services will allow the central collection, integration and provision of ASM data in support of continuous collaborative network processes, in such a way improving operational performance during the planning and execution phases (predictability, flexibility, better use of capacity, enhanced flight efficiency, real time sharing of information, better management of available airspace. Discussion: Given the important contribution that AFUA brings into air traffic management

  2. Flexible Learning Itineraries Based on Conceptual Maps

    OpenAIRE

    Olga Lucía Agudelo; Jesus Salinas Ibáñez

    2015-01-01

    The use of learning itineraries based on conceptual maps is studied in order to propose a more flexible instructional design that strengthens the learning process focused on the student, generating non-linear processes, characterising its elements, setting up relationships between them and shaping a general model with specifications for each educational level. Through a methodology built on the Successive Approximation Model (SAM), this article studies learning itinerary design, implementatio...

  3. NONLINEAR DYNAMIC ANALYSIS OF FLEXIBLE MULTIBODY SYSTEM

    Institute of Scientific and Technical Information of China (English)

    A.Y.T.Leung; WuGuorong; ZhongWeifang

    2004-01-01

    The nonlinear dynamic equations of a multibody system composed of flexible beams are derived by using the Lagrange multiplier method. The nonlinear Euler beam theory with inclusion of axial deformation effect is employed and its deformation field is described by exact vibration modes. A numerical procedure for solving the dynamic equations is presented based on the Newmark direct integration method combined with Newton-Raphson iterative method. The results of numerical examples prove the correctness and efficiency of the method proposed.

  4. Simulating charge transport in flexible systems

    Directory of Open Access Journals (Sweden)

    Timothy Clark

    2015-12-01

    Full Text Available Systems in which movements occur on two significantly different time domains, such as organic electronic components with flexible molecules, require different simulation techniques for the two time scales. In the case of molecular electronics, charge transport is complicated by the several different mechanisms (and theoretical models that apply in different cases. We cannot yet combine time scales of molecular and electronic movement in simulations of real systems. This review describes our progress towards this goal.

  5. A more flexible lipoprotein sorting pathway.

    Science.gov (United States)

    Chahales, Peter; Thanassi, David G

    2015-05-01

    Lipoprotein biogenesis in Gram-negative bacteria occurs by a conserved pathway, each step of which is considered essential. In contrast to this model, LoVullo and colleagues demonstrate that the N-acyl transferase Lnt is not required in Francisella tularensis or Neisseria gonorrhoeae. This suggests the existence of a more flexible lipoprotein pathway, likely due to a modified Lol transporter complex, and raises the possibility that pathogens may regulate lipoprotein processing to modulate interactions with the host. PMID:25755190

  6. The illness flexibility model and sickness absence

    OpenAIRE

    Johansson, Gun

    2007-01-01

    Research on sickness absence has repeatedly been described as theoretically undeveloped. In this thesis the model of illness flexibility is introduced. In this model, sickness absence is assumed to be caused by people’s ability and motivation to work. Ability and motivation will in turn be affected by conditions met in and outside work. In the model, five basic components are discerned describing such conditions. Adjustment latitude describes opportunities to adjust work to ...

  7. Flexible Structural-Health-Monitoring Sheets

    Science.gov (United States)

    Qing, Xinlin; Kuo, Fuo

    2008-01-01

    A generic design for a type of flexible structural-health-monitoring sheet with multiple sensor/actuator types and a method of manufacturing such sheets has been developed. A sheet of this type contains an array of sensing and/or actuation elements, associated wires, and any other associated circuit elements incorporated into various flexible layers on a thin, flexible substrate. The sheet can be affixed to a structure so that the array of sensing and/or actuation elements can be used to analyze the structure in accordance with structural-health-monitoring techniques. Alternatively, the sheet can be designed to be incorporated into the body of the structure, especially if the structure is made of a composite material. Customarily, structural-health monitoring is accomplished by use of sensors and actuators arrayed at various locations on a structure. In contrast, a sheet of the present type can contain an entire sensor/actuator array, making it unnecessary to install each sensor and actuator individually on or in a structure. Sensors of different types such as piezoelectric and fiber-optic can be embedded in the sheet to form a hybrid sensor network. Similarly, the traces for electric communication can be deposited on one or two layers as required, and an entirely separate layer can be employed to shield the sensor elements and traces.

  8. Silk Fibroin for Flexible Electronic Devices.

    Science.gov (United States)

    Zhu, Bowen; Wang, Hong; Leow, Wan Ru; Cai, Yurong; Loh, Xian Jun; Han, Ming-Yong; Chen, Xiaodong

    2016-06-01

    Flexible electronic devices are necessary for applications involving unconventional interfaces, such as soft and curved biological systems, in which traditional silicon-based electronics would confront a mechanical mismatch. Biological polymers offer new opportunities for flexible electronic devices by virtue of their biocompatibility, environmental benignity, and sustainability, as well as low cost. As an intriguing and abundant biomaterial, silk offers exquisite mechanical, optical, and electrical properties that are advantageous toward the development of next-generation biocompatible electronic devices. The utilization of silk fibroin is emphasized as both passive and active components in flexible electronic devices. The employment of biocompatible and biosustainable silk materials revolutionizes state-of-the-art electronic devices and systems that currently rely on conventional semiconductor technologies. Advances in silk-based electronic devices would open new avenues for employing biomaterials in the design and integration of high-performance biointegrated electronics for future applications in consumer electronics, computing technologies, and biomedical diagnosis, as well as human-machine interfaces. PMID:26684370

  9. Ultrathin flexible dual band terahertz absorber

    Science.gov (United States)

    Shan, Yan; Chen, Lin; Shi, Cheng; Cheng, Zhaoxiang; Zang, Xiaofei; Xu, Boqing; Zhu, Yiming

    2015-09-01

    We propose an ultrathin and flexible dual band absorber operated at terahertz frequencies based on metamaterial. The metamaterial structure consists of periodical split ring resonators with two asymmetric gaps and a metallic ground plane, separated by a thin-flexible dielectric spacer. Particularly, the dielectric spacer is a free-standing polyimide film with thickness of 25 μm, resulting in highly flexible for our absorber and making it promising for non-planar applications such as micro-bolometers and stealth aircraft. Experimental results show that the absorber has two resonant absorption frequencies (0.41 THz and 0.75 THz) with absorption rates 92.2% and 97.4%, respectively. The resonances at the absorption frequencies come from normal dipole resonance and high-order dipole resonance which is inaccessible in the symmetrical structure. Multiple reflection interference theory is used to analyze the mechanism of the absorber and the results are in good agreement with simulated and experimental results. Furthermore, the absorption properties are studied under various spacer thicknesses. This kind of metamaterial absorber is insensitive to polarization, has high absorption rates (over 90%) with wide incident angles range from 0° to 45° and the absorption rates are also above 90% when wrapping it to a curved surface.

  10. Symptomatic flexible flatfoot in adults: subtalar arthroereisis

    Science.gov (United States)

    Ozan, Fırat; Doğar, Fatih; Gençer, Kürşat; Koyuncu, Şemmi; Vatansever, Fatih; Duygulu, Fuat; Altay, Taşkın

    2015-01-01

    Flexible flatfoot is a common deformity in pediatric and adult populations. In this study, we aimed to evaluate the functional and radiographic results of subtalar arthroereisis in adult patients with symptomatic flexible flatfoot. We included 26 feet in 16 patients who underwent subtalar arthroereisis for symptomatic flexible flatfoot. Radiographic examination included calcaneal inclination angle, lateral talocalcaneal angle, Meary’s angle, anteroposterior talonavicular angle, and Kite’s angle. The clinical assessment was based on the American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot scale and a visual analog scale (VAS). The mean follow-up was 15.1±4.7 months. The mean preoperative AOFAS score was 53±6.6, while the mean AOFAS score at the last follow-up visit was 75±11.2 (P0.05); 8°±5.3° and 3.3±3 for Meary’s angles (Pflatfoot. This procedure provided radiological and functional recovery in our series of patients. PMID:26527876

  11. Polymer flexibility and turbulent drag reduction.

    Science.gov (United States)

    Gillissen, J J J

    2008-10-01

    Polymer-induced drag reduction is the phenomenon by which the friction factor of a turbulent flow is reduced by the addition of small amounts of high-molecular-weight linear polymers, which conformation in solution at rest can vary between randomly coiled and rodlike. It is well known that drag reduction is positively correlated to viscous stresses, which are generated by extended polymers. Rodlike polymers always assume this favorable conformation, while randomly coiling chains need to be unraveled by fluid strain rate in order to become effective. The coiling and stretching of flexible polymers in turbulent flow produce an additional elastic component in the polymer stress. The effect of the elastic stresses on drag reduction is unclear. To study this issue, we compare direct numerical simulations of turbulent drag reduction in channel flow using constitutive equations describing solutions of rigid and flexible polymers. When compared at constant phi r2, both simulations predict the same amount of drag reduction. Here phi is the polymer volume fraction and r is the polymer aspect ratio, which for flexible polymers is based on average polymer extension at the channel wall. This demonstrates that polymer elasticity plays a marginal role in the mechanism for drag reduction.

  12. An Efficient Method for Simulating Flexible Connectors

    Directory of Open Access Journals (Sweden)

    Frederick Li

    2009-04-01

    Full Text Available Physically-based dynamic simulation has been an active research area for many years. It is an important technique to enhance the realism of interactive multimedia or computer graphics applications. However, while most of these applications require real-time performance to handle user interactions, dynamic simulation is generally expensive computationally, as simulating a flexible (non-rigid object is typically done by modeling it with a large number of rigid bodies, in which constraints or impulses among the rigid bodies need to be processed continuously. In addition, in an interactive type of application, the motion of rigid bodies may sometimes be intervened. Such interactions, however, cannot be modeled with typical dynamic simulation techniques, such as associating constraints or behavior functions to the rigid bodies, due to its unpredictable nature. In this paper, we present a method for simulating flexible connectors. Our method combines dynamic constraints and impulse-based simulation to support real-time simulation of flexible connectors, such as ropes or chains. It also handles dynamic interventions efficiently.

  13. Viscous pumping inspired by flexible propulsion

    CERN Document Server

    Arco, Roger M; Lauga, Eric; Zenit, Roberto

    2014-01-01

    Fluid-suspended microorganisms have evolved different swimming and feeding strategies in order to cope with an environment dominated by viscous effects. For instance ciliated organisms rely on the collective motion of flexible appendices to move and feed. By performing a non-reciprocal motion, flexible filaments can produce a net propulsive force, or pump fluid, in the absence of inertia. Inspired by such fundamental concept, we propose a strategy to produce macroscopic pumping and mixing in creeping flow. We measure experimentally the net motion of a Newtonian viscous fluid induced by the reciprocal motion of a flapper. When the flapper is rigid no net motion is induced. In contrast, when the flapper is made of a flexible material, a net fluid pumping is measured. We quantify the effectiveness of this pumping strategy and show that optimal pumping is achieved when the length of the flapper is on the same order as the elasto-hydrodynamic penetration length. We finally discuss the possible applications of flex...

  14. On the flexibility of phonetic categories

    Science.gov (United States)

    Francis, Alexander L.; Nusbaum, Howard C.

    2002-05-01

    Research on phonetic category acquisition suggests that over the course of development children shift the relative weight given to various acoustic cues to particular phonetic categories [S. Nittrouer, J. Phon. 20, 1-32 (1992)]. Adults also show flexibility in acquiring second language categories and learning to recognize synthetic speech. In both cases listeners must shift attention among some acoustic cues and change the weighting and mapping of others. Recent research demonstrated that category-level feedback can induce adult listeners to shift attention between conflicting cues to native stop-consonant categories. Subsequent research showed that adult listeners also reorganize the distribution of their attention to acoustic cues in learning to better understand synthetic speech. Moreover, research on learning foreign phonetic contrasts suggests that listeners can learn to direct attention to unfamiliar acoustic cues. These results suggest that phonetic categories are flexible in terms of the nature and quality of the acoustic cues that define them. We argue that this flexibility is a consequence of the basic nature of the general mechanism that mediates speech perception: In order to resolve the problem of context-conditioned variability, listeners must dynamically modify attention to the acoustic signal in a context-dependent manner.

  15. The Selective Autophagy Receptor p62 Forms a Flexible Filamentous Helical Scaffold

    Directory of Open Access Journals (Sweden)

    Rodolfo Ciuffa

    2015-05-01

    Full Text Available The scaffold protein p62/SQSTM1 is involved in protein turnover and signaling and is commonly found in dense protein bodies in eukaryotic cells. In autophagy, p62 acts as a selective autophagy receptor that recognizes and shuttles ubiquitinated proteins to the autophagosome for degradation. The structural organization of p62 in cellular bodies and the interplay of these assemblies with ubiquitin and the autophagic marker LC3 remain to be elucidated. Here, we present a cryo-EM structural analysis of p62. Together with structures of assemblies from the PB1 domain, we show that p62 is organized in flexible polymers with the PB1 domain constituting a helical scaffold. Filamentous p62 is capable of binding LC3 and addition of long ubiquitin chains induces disassembly and shortening of filaments. These studies explain how p62 assemblies provide a large molecular scaffold for the nascent autophagosome and reveal how they can bind ubiquitinated cargo.

  16. Monte Carlo simulations of flexible polyanions complexing with whey proteins at their isoelectric point

    Science.gov (United States)

    de Vries, R.

    2004-02-01

    Electrostatic complexation of flexible polyanions with the whey proteins α-lactalbumin and β-lactoglobulin is studied using Monte Carlo simulations. The proteins are considered at their respective isoelectric points. Discrete charges on the model polyelectrolytes and proteins interact through Debye-Hückel potentials. Protein excluded volume is taken into account through a coarse-grained model of the protein shape. Consistent with experimental results, it is found that α-lactalbumin complexes much more strongly than β-lactoglobulin. For α-lactalbumin, strong complexation is due to localized binding to a single large positive "charge patch," whereas for β-lactoglobulin, weak complexation is due to diffuse binding to multiple smaller charge patches.

  17. Applying flexible molecular docking to simulate protein retention behavior in hydrophobic interaction chromatography

    Institute of Scientific and Technical Information of China (English)

    ZHOU; Peng; TIAN; FeiFei; LI; ZhiLiang

    2007-01-01

    Interaction between proteins and stationary phase in hydrophobic interaction chromatography (HIC) is differentiated into two thermodynamic processes involving direct nonbonding/conformation interaction and surface hydrophobic effect of proteins, hence quantitatively giving rise to a binary linear relation between HIC retention time (RT) at concentrated salting liquid and ligand-protein binding free energy. Then, possible binding manners for 27 proteins of known crystal structures with hydrophobic ligands are simulated and analyzed via ICM flexible molecular docking and genetic algorithm, with results greatly consistent with experimental values. By investigation, it is confirmed local hydrophobic effects of proteins and nonbinding/conformation interaction between ligand and protein both notably influence HIC chromatogram retention behaviors, mainly focusing on exposed portions on the protein surface.

  18. MEASUREMENT AND DECOMPOSITION OF FLEXIBILITY OF MULTI-OUTPUT FIRMS

    OpenAIRE

    Renner, Swetlana; Glauben, Thomas; Hockmann, Heinrich

    2012-01-01

    Flexibility can be considered as a crucial factor of competitive advantage, especially under conditions of dynamically changing environments. Based on the classical microeconomic definition of flexibility, as introduced by Stigler, and some recent concepts developed in the production economics, this article proposes a primal flexibility measure for multi-product firms. When decomposed, this measure offers useful insights into possible sources of flexibility, especially by investigating the ro...

  19. Flexible employment as a unidirectional career? Results from field experiments

    OpenAIRE

    Boerner, Elisabeth; Boerner, Sabine

    2009-01-01

    Although the number of flexible workers is constantly growing, little is known about career paths built up on flexible employment. In this article, we investigate the chances of former flexible workers to be employed in a permanent full-time position. In two field experiments, we asked for employers evaluation of applicants with a flexible employment history. Results indicate that former part-time work is in fact perceived as a disadvantage for candidates when applying for a permanent full-t...

  20. Free-form Flexible Lithium-Ion Microbattery

    KAUST Repository

    Kutbee, Arwa

    2016-03-02

    Wearable electronics need miniaturized, safe and flexible power sources. Lithium ion battery is a strong candidate as high performance flexible battery. The development of flexible materials for battery electrodes suffers from the limited material choices. In this work, we present integration strategy to rationally design materials and processes to report flexible inorganic lithium-ion microbattery with no restrictions on the materials used. The battery shows an enhanced normalized capacity of 147 μAh/cm2 when bent.

  1. 3D Position Tracking System for Flexible Cystoscopy

    OpenAIRE

    Munehiro Nakamura; Yusuke Kajiwara; Tatsuhito Hasegawa; Haruhiko Kimura

    2013-01-01

    Flexible cystoscopy is an examination that allows physicians to look inside the bladder. In flexible cystoscopy, beginner physicians tend to lose track of the observation due to complex handling patterns of a flexible cystoscope and poor characteristics of the bladder. In this paper, as a diagnostic support tool for beginner physicians in flexible cystoscopy, we propose a system for tracking the observation using cystoscopic images. Our system discriminates three handling patterns of a flexib...

  2. MULTI-FLEXIBLE SYSTEM DYNAMIC MODELING THEORY AND APPLICATION

    Institute of Scientific and Technical Information of China (English)

    仲昕; 周兵; 杨汝清

    2001-01-01

    The flexible body modeling theory was demonstrated. An example of modeling a kind of automobile's front suspension as a multi-flexible system was shown. Finally, it shows that the simulation results of multi-flexible dynamic model more approach the road test data than those of multi-rigid dynamic model do. Thus, it is fully testified that using multi-flexible body theory to model is necessary and effective.

  3. Active vibration control techniques for flexible space structures

    Science.gov (United States)

    Parlos, Alexander G.; Jayasuriya, Suhada

    1990-01-01

    Two proposed control system design techniques for active vibration control in flexible space structures are detailed. Control issues relevant only to flexible-body dynamics are addressed, whereas no attempt was made to integrate the flexible and rigid-body spacecraft dynamics. Both of the proposed approaches revealed encouraging results; however, further investigation of the interaction of the flexible and rigid-body dynamics is warranted.

  4. Flexible lithium-ion planer thin-film battery

    KAUST Repository

    Kutbee, Arwa T.

    2016-02-03

    Commercialization of wearable electronics requires miniaturized, flexible power sources. Lithium ion battery is a strong candidate as the next generation high performance flexible battery. The development of flexible materials for battery electrodes suffers from the limited material choices. In this work, we present a flexible inorganic lithium-ion battery with no restrictions on the materials used. The battery showed an enhanced normalized capacity of 146 ??Ah/cm2.

  5. Wage Flexibility and Economic Performance; Evidence Across Industrial Countries

    OpenAIRE

    Magda E. Kandil

    2000-01-01

    This paper provides new empirical evidence on the degree of nominal wage flexibility in a sample of nineteen industrial countries. Across countries, aggregate uncertainty increases the degree of wage flexibility in the face of various shocks. Wage flexibility stabilizes fluctuations in real output and guarantees workers a higher real standard of living in response to aggregate demand shocks. Wage flexibility in response to energy price shocks guarantees workers higher real wages without exace...

  6. Protein localization with flexible DNA or RNA.

    Science.gov (United States)

    Bernhardsson, Sebastian; Mitarai, Namiko; Sneppen, Kim

    2012-01-01

    Localization of activity is ubiquitous in life, and also within sub-cellular compartments. Localization provides potential advantages as different proteins involved in the same cellular process may supplement each other on a fast timescale. It might also prevent proteins from being active in other regions of the cell. However localization is at odds with the spreading of unbound molecules by diffusion. We model the cost and gain for specific enzyme activity using localization strategies based on binding to sites of intermediate specificity. While such bindings in themselves decrease the activity of the protein on its target site, they may increase protein activity if stochastic motion allows the acting protein to touch both the intermediate binding site and the specific site simultaneously. We discuss this strategy in view of recent suggestions on long non-coding RNA as a facilitator of localized activity of chromatin modifiers. PMID:22347995

  7. Protein localization with flexible DNA or RNA.

    Directory of Open Access Journals (Sweden)

    Sebastian Bernhardsson

    Full Text Available Localization of activity is ubiquitous in life, and also within sub-cellular compartments. Localization provides potential advantages as different proteins involved in the same cellular process may supplement each other on a fast timescale. It might also prevent proteins from being active in other regions of the cell. However localization is at odds with the spreading of unbound molecules by diffusion. We model the cost and gain for specific enzyme activity using localization strategies based on binding to sites of intermediate specificity. While such bindings in themselves decrease the activity of the protein on its target site, they may increase protein activity if stochastic motion allows the acting protein to touch both the intermediate binding site and the specific site simultaneously. We discuss this strategy in view of recent suggestions on long non-coding RNA as a facilitator of localized activity of chromatin modifiers.

  8. Alcohol Binding to the Odorant Binding Protein LUSH: Multiple Factors Affecting Binding Affinities

    OpenAIRE

    Ader, Lauren; Jones, David N. M.; Lin, Hai

    2010-01-01

    Density function theory (DFT) calculations have been carried out to investigate the binding of alcohols to the odorant binding protein LUSH from Drosophila melanogaster. LUSH is one of the few proteins known to bind to ethanol at physiologically relevant concentrations and where high-resolution structural information is available for the protein bound to alcohol at these concentrations. The structures of the LUSH–alcohol complexes identify a set of specific hydrogen-bonding interactions as cr...

  9. Flexible Training Strategy (National Task Force on Medical Staffing)

    OpenAIRE

    Department of Health

    2003-01-01

    Flexible Training Strategy (National Task Force on Medical Staffing) The Flexible Training Strategy, while endorsing flexible/part-time options recognises that the preferred option for the majority of doctors-in-training and consultants is most likely to continue to be full-time training and work. Click here to download PDF

  10. 5 CFR 532.513 - Flexible and compressed work schedules.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Flexible and compressed work schedules... REGULATIONS PREVAILING RATE SYSTEMS Premium Pay and Differentials § 532.513 Flexible and compressed work schedules. Federal Wage System employees who are authorized to work flexible and compressed work...

  11. 75 FR 34445 - Audit Program for Texas Flexible Permit Holders

    Science.gov (United States)

    2010-06-17

    ... AGENCY Audit Program for Texas Flexible Permit Holders AGENCY: Environmental Protection Agency (EPA). ACTION: Notice of Clean Air Act voluntary compliance audit program for flexible permit holders in the State of Texas; request for public comment. SUMMARY: EPA is offering holders of Texas flexible...

  12. 49 CFR 178.710 - Standards for flexible IBCs.

    Science.gov (United States)

    2010-10-01

    ... PACKAGINGS IBC Performance-Oriented Standards § 178.710 Standards for flexible IBCs. (a) The provisions of this section apply to flexible IBCs intended to contain solid hazardous materials. Flexible IBC types... body of the IBC or formed from a continuation of the IBC body material. (c) Construction...

  13. Capacity flexibility allocation in an outsourced supply chain with reservation

    DEFF Research Database (Denmark)

    Boulaksil, Youssef; Grunow, Martin; Fransoo, J.C.

    2011-01-01

    the capacity flexibility to the different outsourcers by maximizing the expected profit. Offering more flexibility to the more uncertain outsourcer generates higher expected revenue, but also increases the expected penalty costs. The allocated capacity flexibilities (determined at the tactical level) are input...

  14. A Flex-market Design for Flexibility Services through DERs

    DEFF Research Database (Denmark)

    Zhang, Chunyu; Ding, Yi; Østergaard, Jacob;

    2013-01-01

    in this paper. With the brand new notion of Flexibility Clearing House (FLECH), the proposed Flex-market has the ability to promote small scale DERs (up to 5MW) to participate in flexibility services trading. Accordingly, efforts to relieve the congestions in local grid areas, the contractual flexibility...

  15. Performance measurement of supply chain flexibility using witness

    Directory of Open Access Journals (Sweden)

    Rituraj Chandrakar

    2012-10-01

    Full Text Available In today’s global scenario of intense competition and environmental uncertainty flexibility in supply chain has an important role to play for the existence of any supply chain business. A need to be responsive to the constantly changing market scenario and cater to the customer needs, a certain degree of flexibility is required, which requires the coordination of many plants to produce and deliver goods to customers located in different places, and suppliers, which provide each plant with the required components. This paper intends to measure the degree of flexibility required for a two stage supply chain and assessing both the supplier flexibility and the assembler flexibility. In this paper, nine configurations of the SC are considered resulting from the combination of the three degrees of supplier and manufacturer flexibility, i.e. no flexibility, limited flexibility and total flexibility, respectively. Simulation model representing the different flexibility configurations are evaluated and the performance of each configuration analyzed to determine the flexibility configuration suitable to a supply chain. In particular the performance analysis of lead time, work-in-process, service level and cost are measured to determine the suitable flexibility.

  16. Flexible automation and the loss of pooling synergy

    NARCIS (Netherlands)

    Slomp, Jannes; Zee, Durk-Jouke van der

    2001-01-01

    This paper focuses on the effects of flexible automation on the performance of a job shop. Flexible automated machines may significantly improve the delivery performance and the flow time of jobs. The insertion of a flexible automated system in a job shop, however, also has a counter effect on the m

  17. Binding Mechanisms of Intrinsically Disordered Proteins: Theory, Simulation, and Experiment

    Science.gov (United States)

    Mollica, Luca; Bessa, Luiza M.; Hanoulle, Xavier; Jensen, Malene Ringkjøbing; Blackledge, Martin; Schneider, Robert

    2016-01-01

    In recent years, protein science has been revolutionized by the discovery of intrinsically disordered proteins (IDPs). In contrast to the classical paradigm that a given protein sequence corresponds to a defined structure and an associated function, we now know that proteins can be functional in the absence of a stable three-dimensional structure. In many cases, disordered proteins or protein regions become structured, at least locally, upon interacting with their physiological partners. Many, sometimes conflicting, hypotheses have been put forward regarding the interaction mechanisms of IDPs and the potential advantages of disorder for protein-protein interactions. Whether disorder may increase, as proposed, e.g., in the “fly-casting” hypothesis, or decrease binding rates, increase or decrease binding specificity, or what role pre-formed structure might play in interactions involving IDPs (conformational selection vs. induced fit), are subjects of intense debate. Experimentally, these questions remain difficult to address. Here, we review experimental studies of binding mechanisms of IDPs using NMR spectroscopy and transient kinetic techniques, as well as the underlying theoretical concepts and numerical methods that can be applied to describe these interactions at the atomic level. The available literature suggests that the kinetic and thermodynamic parameters characterizing interactions involving IDPs can vary widely and that there may be no single common mechanism that can explain the different binding modes observed experimentally. Rather, disordered proteins appear to make combined use of features such as pre-formed structure and flexibility, depending on the individual system and the functional context.

  18. Binding Mechanisms of Intrinsically Disordered Proteins: Theory, Simulation, and Experiment

    Science.gov (United States)

    Mollica, Luca; Bessa, Luiza M.; Hanoulle, Xavier; Jensen, Malene Ringkjøbing; Blackledge, Martin; Schneider, Robert

    2016-01-01

    In recent years, protein science has been revolutionized by the discovery of intrinsically disordered proteins (IDPs). In contrast to the classical paradigm that a given protein sequence corresponds to a defined structure and an associated function, we now know that proteins can be functional in the absence of a stable three-dimensional structure. In many cases, disordered proteins or protein regions become structured, at least locally, upon interacting with their physiological partners. Many, sometimes conflicting, hypotheses have been put forward regarding the interaction mechanisms of IDPs and the potential advantages of disorder for protein-protein interactions. Whether disorder may increase, as proposed, e.g., in the “fly-casting” hypothesis, or decrease binding rates, increase or decrease binding specificity, or what role pre-formed structure might play in interactions involving IDPs (conformational selection vs. induced fit), are subjects of intense debate. Experimentally, these questions remain difficult to address. Here, we review experimental studies of binding mechanisms of IDPs using NMR spectroscopy and transient kinetic techniques, as well as the underlying theoretical concepts and numerical methods that can be applied to describe these interactions at the atomic level. The available literature suggests that the kinetic and thermodynamic parameters characterizing interactions involving IDPs can vary widely and that there may be no single common mechanism that can explain the different binding modes observed experimentally. Rather, disordered proteins appear to make combined use of features such as pre-formed structure and flexibility, depending on the individual system and the functional context. PMID:27668217

  19. Binding Energy and Enzymatic Catalysis.

    Science.gov (United States)

    Hansen, David E.; Raines, Ronald T.

    1990-01-01

    Discussed is the fundamental role that the favorable free energy of binding of the rate-determining transition state plays in catalysis. The principle that all of the catalytic factors discussed are realized by the use of this binding energy is reviewed. (CW)

  20. A deep learning framework for modeling structural features of RNA-binding protein targets.

    Science.gov (United States)

    Zhang, Sai; Zhou, Jingtian; Hu, Hailin; Gong, Haipeng; Chen, Ligong; Cheng, Chao; Zeng, Jianyang

    2016-02-29

    RNA-binding proteins (RBPs) play important roles in the post-transcriptional control of RNAs. Identifying RBP binding sites and characterizing RBP binding preferences are key steps toward understanding the basic mechanisms of the post-transcriptional gene regulation. Though numerous computational methods have been developed for modeling RBP binding preferences, discovering a complete structural representation of the RBP targets by integrating their available structural features in all three dimensions is still a challenging task. In this paper, we develop a general and flexible deep learning framework for modeling structural binding preferences and predicting binding sites of RBPs, which takes (predicted) RNA tertiary structural information into account for the first time. Our framework constructs a unified representation that characterizes the structural specificities of RBP targets in all three dimensions, which can be further used to predict novel candidate binding sites and discover potential binding motifs. Through testing on the real CLIP-seq datasets, we have demonstrated that our deep learning framework can automatically extract effective hidden structural features from the encoded raw sequence and structural profiles, and predict accurate RBP binding sites. In addition, we have conducted the first study to show that integrating the additional RNA tertiary structural features can improve the model performance in predicting RBP binding sites, especially for the polypyrimidine tract-binding protein (PTB), which also provides a new evidence to support the view that RBPs may own specific tertiary structural binding preferences. In particular, the tests on the internal ribosome entry site (IRES) segments yield satisfiable results with experimental support from the literature and further demonstrate the necessity of incorporating RNA tertiary structural information into the prediction model. The source code of our approach can be found in https