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Sample records for binds flexible gc-rich

  1. The flexible loop L1 of the H3K4 demethylase JARID1B ARID domain has a crucial role in DNA-binding activity

    International Nuclear Information System (INIS)

    Yao, Wenming; Peng, Yu; Lin, Donghai

    2010-01-01

    JARID1B, a member of the JmjC demethylase family, has a crucial role in H3K4me3 demethylation. The ARID domain is a potential DNA-binding domain of JARID1B. Previous studies indicate that a GC-rich DNA motif is the specific target of the ARID domain. However, the details of the interaction between the ARID domain and duplex DNA require further study. Here, we utilized NMR spectroscopy to assign the backbone amino acids and mapped the DNA-binding sites of the human JARID1B ARID domain. Perturbations to 1 H- 15 N correlation spectra revealed that the flexible loop L1 of ARID was the main DNA-binding interface. EMSA and intrinsic fluorescence experiments demonstrated that mutations on loop L1 strongly reduced the DNA-binding activity of JARID1B ARID. Furthermore, transfection of mutant forms resulted in a distinct loss of intrinsic H3K4 demethylase activity, implying that the flexible loop L1 made a major contribution to sustaining the DNA-binding ability of JARID1B ARID domain.

  2. Amino Acid Usage Is Asymmetrically Biased in AT- and GC-Rich Microbial Genomes

    DEFF Research Database (Denmark)

    Bohlin, Jon; Brynildsrud, Ola Brønstad; Vesth, Tammi Camilla

    2013-01-01

    frequencies were distributed in over 2000 microbial genomes and how these distributions were affected by base compositional changes. In addition, we wanted to know how genome-wide amino acid usage was biased in the different genomes and how changes to base composition and mutations affected this bias...... purifying selection than genomes with higher AAUB. Conclusion: Genomic base composition has a substantial effect on both amino acid- and codon frequencies in bacterial genomes. While phylogeny influenced amino acid usage more in GC-rich genomes, AT-content was driving amino acid usage in AT-rich genomes. We...

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

    Science.gov (United States)

    Kostyuk, Svetlana; Smirnova, Tatiana; Kameneva, Larisa; Porokhovnik, Lev; Speranskij, Anatolij; Ershova, Elizaveta; Stukalov, Sergey; Izevskaya, Vera; Veiko, Natalia

    2015-01-01

    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. 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). 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.

  4. Trans-acting GC-rich non-coding RNA at var expression site modulates gene counting in malaria parasite.

    Science.gov (United States)

    Guizetti, Julien; Barcons-Simon, Anna; Scherf, Artur

    2016-11-16

    Monoallelic expression of the var multigene family enables immune evasion of the malaria parasite Plasmodium falciparum in its human host. At a given time only a single member of the 60-member var gene family is expressed at a discrete perinuclear region called the 'var expression site'. However, the mechanism of var gene counting remains ill-defined. We hypothesize that activation factors associating specifically with the expression site play a key role in this process. Here, we investigate the role of a GC-rich non-coding RNA (ncRNA) gene family composed of 15 highly homologous members. GC-rich genes are positioned adjacent to var genes in chromosome-central gene clusters but are absent near subtelomeric var genes. Fluorescence in situ hybridization demonstrates that GC-rich ncRNA localizes to the perinuclear expression site of central and subtelomeric var genes in trans. Importantly, overexpression of distinct GC-rich ncRNA members disrupts the gene counting process at the single cell level and results in activation of a specific subset of var genes in distinct clones. We identify the first trans-acting factor targeted to the elusive perinuclear var expression site and open up new avenues to investigate ncRNA function in antigenic variation of malaria and other protozoan pathogens. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  5. Conformational flexibility of avidin: the influence of biotin binding

    International Nuclear Information System (INIS)

    Soledad Celej, M.; Montich, Guillermo G.; Fidelio, Gerardo D.

    2004-01-01

    Ligand binding to proteins is a key process in cell biochemistry. The interaction usually induces modifications in the unfolding thermodynamic parameters of the macromolecule due to the coupling of unfolding and binding equilibria. In addition, these modifications can be attended by changes in protein structure and/or conformational flexibility induced by ligand binding. In this work, we have explored the effect of biotin binding on conformation and dynamic properties of avidin by using infrared spectroscopy including kinetics of hydrogen/deuterium exchange. Our results, along with previously thermodynamic published data, indicate a clear correlation between thermostability and protein compactness. In addition, our results also help to interpret the thermodynamic binding parameters of the exceptionally stable biotin:AVD complex

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

    Directory of Open Access Journals (Sweden)

    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.

  7. Amplification of a GC-rich heterochromatin in the freshwater fish Leporinus desmotes (Characiformes, Anostomidae

    Directory of Open Access Journals (Sweden)

    Vladimir Pavan Margarido

    2000-09-01

    Full Text Available This is the first description of the karyotype of Leporinus desmotes. The diploid female number was 2n = 54 meta- and submetacentric chromosomes. The nucleolar organizing regions (NORs were studied by silver nitrate staining and rDNA fluorescence in situ hybridization (FISH and were found to be located in the telomeric region of the long arm of the 9th pair. C-banding revealed centromeric and telomeric heterochromatin segments in most chromosomes. Intercalar blocks of heterochromatin were observed in the long arm of six chromosome pairs. Besides a NOR-adjacent heterochromatin, all of the intercalar heterochromatic segments were brightly fluorescent by mithramycin staining. These data suggest that a unique amplification of a primordial GC-rich heterochromatin, probably NOR-associated, may have taken place in the karyotype diversification of this Leporinus species.Esta é a primeira descrição do cariótipo de Leporinus desmotes fêmea. O número diplóide encontrado foi 2n = 54 cromossomos meta- e submetacêntricos. As regiões organizadoras de nucléolos (NORs foram estudadas através da impregnação pela prata e por hibridização in situ com sondas de DNAr (FISH, e foram localizadas na região telomérica do braço longo do 9º par. Heterocromatinas centromérica e telomérica foram reveladas pelo bandamento C na maioria dos cromossomos. Adicionalmente, grande quantidade de heterocromatina intercalar ou subtelomérica foi também observada. Diferenciação composicional na maior parte da heterocromatina identificada em L. desmotes pode ser inferida através da coloração pela mitramicina, caracterizando um caso peculiar de amplificação de segmentos heterocromáticos ricos em bases GC neste grupo de peixes.

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

    Science.gov (United States)

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

    2016-08-02

    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. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  9. Transcriptional activation of transforming growth factor alpha by estradiol: requirement for both a GC-rich site and an estrogen response element half-site.

    Science.gov (United States)

    Vyhlidal, C; Samudio, I; Kladde, M P; Safe, S

    2000-06-01

    17beta-Estradiol (E2) induces transforming growth factor alpha (TGFalpha) gene expression in MCF-7 cells and previous studies have identified a 53 bp (-252 to -200) sequence containing two imperfect estrogen responsive elements (EREs) that contribute to E2 responsiveness. Deletion analysis of the TGFalpha gene promoter in this study identified a second upstream region of the promoter (-623 to -549) that is also E2 responsive. This sequence contains three GC-rich sites and an imperfect ERE half-site, and the specific cis-elements and trans-acting factors were determined by promoter analysis in transient transfection experiments, gel mobility shift assays and in vitro DNA footprinting. The results are consistent with an estrogen receptor alpha (ERalpha)/Sp1 complex interacting with an Sp1(N)(30) ERE half-site ((1/2)) motif in which both ERalpha and Sp1 bind promoter DNA. The ER/Sp1-DNA complex is formed using nuclear extracts from MCF-7 cells but not with recombinant human ERalpha or Sp1 proteins, suggesting that other nuclear factor(s) are required for complex stabilization. The E2-responsive Sp1(N)(x)ERE(1/2) motif identified in the TGFalpha gene promoter has also been characterized in the cathepsin D and heat shock protein 27 gene promoters; however, in the latter two promoters the numbers of intervening nucleotides are 23 and 10 respectively.

  10. 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.

  11. Genomic Mapping of Human DNA provides Evidence of Difference in Stretch between AT and GC rich regions

    Science.gov (United States)

    Reifenberger, Jeffrey; Dorfman, Kevin; Cao, Han

    Human DNA is a not a polymer consisting of a uniform distribution of all 4 nucleic acids, but rather contains regions of high AT and high GC content. When confined, these regions could have different stretch due to the extra hydrogen bond present in the GC basepair. To measure this potential difference, human genomic DNA was nicked with NtBspQI, labeled with a cy3 like fluorophore at the nick site, stained with YOYO, loaded into a device containing an array of nanochannels, and imaged. Over 473,000 individual molecules of DNA, corresponding to roughly 30x coverage of a human genome, were collected and aligned to the human reference. Based on the known AT/GC content between aligned pairs of labels, the stretch was measured for regions of similar size but different AT/GC content. We found that regions of high GC content were consistently more stretched than regions of high AT content between pairs of labels varying in size between 2.5 kbp and 500 kbp. We measured that for every 1% increase in GC content there was roughly a 0.06% increase in stretch. While this effect is small, it is important to take into account differences in stretch between AT and GC rich regions to improve the sensitivity of detection of structural variations from genomic variations. NIH Grant: R01-HG006851.

  12. Thermodynamic model of binding of flexible bivalent haptens to antibody

    Energy Technology Data Exchange (ETDEWEB)

    Dembo, M; Goldstein, B

    1978-01-01

    Studies by Wilder et al. of the binding of Fab' fragments to small haptens have shown that the cross-linking constant (the equilibrium constant for binding an additional Fab' fragment to a hapten-Fab' complex) is strongly dependent on the length of the hapten. We present a simple model for predicting the relationship between the intermolecular cross-linking constant and the monovalent hapten-antibody binding constant. In particular we used the model to obtain the dependence of the cross-linking constant on the length of th hapten, the depth to which the hapten fills th Fab' binding site, and the size of the Fab' fragment. To test the model, we devised expressions which allowed us to analyze the data of Wilder et al. From their data we determined the values of two parameters which we took to be unknown in the theory, the size of the Fab' fragment and the depth to which the hapten fills the Fab' binding site. The values arrived at in this way agreed well with published measurements of these parameters.

  13. Effect of the Flexible Regions of the Oncoprotein Mouse Double Minute X on Inhibitor Binding Affinity.

    Science.gov (United States)

    Qin, Lingyun; Liu, Huili; Chen, Rong; Zhou, Jingjing; Cheng, Xiyao; Chen, Yao; Huang, Yongqi; Su, Zhengding

    2017-11-07

    The oncoprotein MdmX (mouse double minute X) is highly homologous to Mdm2 (mouse double minute 2) in terms of their amino acid sequences and three-dimensional conformations, but Mdm2 inhibitors exhibit very weak affinity for MdmX, providing an excellent model for exploring how protein conformation distinguishes and alters inhibitor binding. The intrinsic conformation flexibility of proteins plays pivotal roles in determining and predicting the binding properties and the design of inhibitors. Although the molecular dynamics simulation approach enables us to understand protein-ligand interactions, the mechanism underlying how a flexible binding pocket adapts an inhibitor has been less explored experimentally. In this work, we have investigated how the intrinsic flexible regions of the N-terminal domain of MdmX (N-MdmX) affect the affinity of the Mdm2 inhibitor nutlin-3a using protein engineering. Guided by heteronuclear nuclear Overhauser effect measurements, we identified the flexible regions that affect inhibitor binding affinity around the ligand-binding pocket on N-MdmX. A disulfide engineering mutant, N-MdmX C25-C110/C76-C88 , which incorporated two staples to rigidify the ligand-binding pocket, allowed an affinity for nutlin-3a higher than that of wild-type N-MdmX (K d ∼ 0.48 vs K d ∼ 20.3 μM). Therefore, this mutant provides not only an effective protein model for screening and designing of MdmX inhibitors but also a valuable clue for enhancing the intermolecular interactions of the pharmacophores of a ligand with pronounced flexible regions. In addition, our results revealed an allosteric ligand-binding mechanism of N-MdmX in which the ligand initially interacts with a compact core, followed by augmenting intermolecular interactions with intrinsic flexible regions. This strategy should also be applicable to many other protein targets to accelerate drug discovery.

  14. Flexibility.

    Science.gov (United States)

    Humphrey, L. Dennis

    1981-01-01

    Flexibility is an important aspect of all sports and recreational activities. Flexibility can be developed and maintained by stretching exercises. Exercises designed to develop flexibility in ankle joints, knees, hips, and the lower back are presented. (JN)

  15. Free energy calculations offer insights into the influence of receptor flexibility on ligand-receptor binding affinities.

    Science.gov (United States)

    Dolenc, Jožica; Riniker, Sereina; Gaspari, Roberto; Daura, Xavier; van Gunsteren, Wilfred F

    2011-08-01

    Docking algorithms for computer-aided drug discovery and design often ignore or restrain the flexibility of the receptor, which may lead to a loss of accuracy of the relative free enthalpies of binding. In order to evaluate the contribution of receptor flexibility to relative binding free enthalpies, two host-guest systems have been examined: inclusion complexes of α-cyclodextrin (αCD) with 1-chlorobenzene (ClBn), 1-bromobenzene (BrBn) and toluene (MeBn), and complexes of DNA with the minor-groove binding ligands netropsin (Net) and distamycin (Dist). Molecular dynamics simulations and free energy calculations reveal that restraining of the flexibility of the receptor can have a significant influence on the estimated relative ligand-receptor binding affinities as well as on the predicted structures of the biomolecular complexes. The influence is particularly pronounced in the case of flexible receptors such as DNA, where a 50% contribution of DNA flexibility towards the relative ligand-DNA binding affinities is observed. The differences in the free enthalpy of binding do not arise only from the changes in ligand-DNA interactions but also from changes in ligand-solvent interactions as well as from the loss of DNA configurational entropy upon restraining.

  16. Small, synthetic, GC-rich mRNA stem-loop modules 5' proximal to the AUG start-codon predictably tune gene expression in yeast.

    Science.gov (United States)

    Lamping, Erwin; Niimi, Masakazu; Cannon, Richard D

    2013-07-29

    A large range of genetic tools has been developed for the optimal design and regulation of complex metabolic pathways in bacteria. However, fewer tools exist in yeast that can precisely tune the expression of individual enzymes in novel metabolic pathways suitable for industrial-scale production of non-natural compounds. Tuning expression levels is critical for reducing the metabolic burden of over-expressed proteins, the accumulation of toxic intermediates, and for redirecting metabolic flux from native pathways involving essential enzymes without negatively affecting the viability of the host. We have developed a yeast membrane protein hyper-expression system with critical advantages over conventional, plasmid-based, expression systems. However, expression levels are sometimes so high that they adversely affect protein targeting/folding or the growth and/or phenotype of the host. Here we describe the use of small synthetic mRNA control modules that allowed us to predictably tune protein expression levels to any desired level. Down-regulation of expression was achieved by engineering small GC-rich mRNA stem-loops into the 5' UTR that inhibited translation initiation of the yeast ribosomal 43S preinitiation complex (PIC). Exploiting the fact that the yeast 43S PIC has great difficulty scanning through GC-rich mRNA stem-loops, we created yeast strains containing 17 different RNA stem-loop modules in the 5' UTR that expressed varying amounts of the fungal multidrug efflux pump reporter Cdr1p from Candida albicans. Increasing the length of mRNA stem-loops (that contained only GC-pairs) near the AUG start-codon led to a surprisingly large decrease in Cdr1p expression; ~2.7-fold for every additional GC-pair added to the stem, while the mRNA levels remained largely unaffected. An mRNA stem-loop of seven GC-pairs (∆G = -15.8 kcal/mol) reduced Cdr1p expression levels by >99%, and even the smallest possible stem-loop of only three GC-pairs (∆G = -4.4 kcal/mol) inhibited

  17. Small, synthetic, GC-rich mRNA stem-loop modules 5′ proximal to the AUG start-codon predictably tune gene expression in yeast

    Science.gov (United States)

    2013-01-01

    Background A large range of genetic tools has been developed for the optimal design and regulation of complex metabolic pathways in bacteria. However, fewer tools exist in yeast that can precisely tune the expression of individual enzymes in novel metabolic pathways suitable for industrial-scale production of non-natural compounds. Tuning expression levels is critical for reducing the metabolic burden of over-expressed proteins, the accumulation of toxic intermediates, and for redirecting metabolic flux from native pathways involving essential enzymes without negatively affecting the viability of the host. We have developed a yeast membrane protein hyper-expression system with critical advantages over conventional, plasmid-based, expression systems. However, expression levels are sometimes so high that they adversely affect protein targeting/folding or the growth and/or phenotype of the host. Here we describe the use of small synthetic mRNA control modules that allowed us to predictably tune protein expression levels to any desired level. Down-regulation of expression was achieved by engineering small GC-rich mRNA stem-loops into the 5′ UTR that inhibited translation initiation of the yeast ribosomal 43S preinitiation complex (PIC). Results Exploiting the fact that the yeast 43S PIC has great difficulty scanning through GC-rich mRNA stem-loops, we created yeast strains containing 17 different RNA stem-loop modules in the 5′ UTR that expressed varying amounts of the fungal multidrug efflux pump reporter Cdr1p from Candida albicans. Increasing the length of mRNA stem-loops (that contained only GC-pairs) near the AUG start-codon led to a surprisingly large decrease in Cdr1p expression; ~2.7-fold for every additional GC-pair added to the stem, while the mRNA levels remained largely unaffected. An mRNA stem-loop of seven GC-pairs (∆G = −15.8 kcal/mol) reduced Cdr1p expression levels by >99%, and even the smallest possible stem-loop of only three GC-pairs (

  18. Transcriptional activation of rat creatine kinase B by 17beta-estradiol in MCF-7 cells involves an estrogen responsive element and GC-rich sites.

    Science.gov (United States)

    Wang, F; Samudio, I; Safe, S

    2001-01-01

    The rat creatine kinase B (CKB) gene is induced by estrogen in the uterus, and constructs containing rat CKB gene promoter inserts are highly estrogen-responsive in cell culture. Analysis of the upstream -568 to -523 region of the promoter in HeLa cells has identified an imperfect palindromic estrogen response element (ERE) that is required for hormone inducibility. Analysis of the CKB gene promoter in MCF-7 breast cancer cells confirmed that pCKB7 (containing the -568 to -523 promoter insert) was estrogen-responsive in transient transfection studies. However, mutation and deletion analysis of this region of the promoter showed that two GC-rich sites and the concensus ERE were functional cis-elements that bound estrogen receptor alpha (ERalpha)/Sp1 and ERalpha proteins, respectively. The role of these elements was confirmed in gel mobility shift and chromatin immunoprecipitation assays and transfection studies in MDA-MB-231 and Schneider Drosophila SL-2 cells. These results show that transcriptional activation of CKB by estrogen is dependent, in part, on ERalpha/Sp1 action which is cell context-dependent. Copyright 2001 Wiley-Liss, Inc.

  19. 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

  20. Flexible goal imitation: Vicarious feedback influences stimulus-response binding by observation.

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    Giesen, Carina; Scherdin, Kerstin; Rothermund, Klaus

    2017-06-01

    This study investigated whether vicarious feedback influences binding processes between stimuli and observed responses. Two participants worked together in a shared color categorization task, taking the roles of actor and observer in turns. During a prime trial, participants saw a word while observing the other person executing a specific response. Automatic binding of words and observed responses into stimulus-response (S-R) episodes was assessed via word repetition effects in a subsequent probe trial in which either the same (compatible) or a different (incompatible) response had to be executed by the participants in response to the same or a different word. Results showed that vicarious prime feedback (i.e., the feedback that the other participant received for her or his response in the prime) modulated S-R retrieval effects: After positive vicarious prime feedback, typical S-R retrieval effects emerged (i.e., performance benefits for stimulus repetition probes with compatible responses, but performance costs for stimulus repetition probes with incompatible responses emerged). Notably, however, S-R-retrieval effects were reversed after vicarious negative prime feedback (meaning that stimulus repetition in the probe resulted in performance costs if prime and probe responses were compatible, and in performance benefits for incompatible responses). Findings are consistent with a flexible goal imitation account, according to which imitation is based on an interpretative and therefore feedback-sensitive reconstruction of action goals from observed movements. In concert with earlier findings, this data support the conclusion that transient S-R binding and retrieval processes are involved in social learning phenomena.

  1. Structures of parasite calreticulins provide insights into their flexibility and dual carbohydrate/peptide-binding properties.

    Science.gov (United States)

    Moreau, Christophe; Cioci, Gianluca; Iannello, Marina; Laffly, Emmanuelle; Chouquet, Anne; Ferreira, Arturo; Thielens, Nicole M; Gaboriaud, Christine

    2016-11-01

    Calreticulin (CRT) is a multifaceted protein, initially discovered as an endoplasmic reticulum (ER) chaperone protein, that is essential in calcium metabolism. Various implications in cancer, early development and immunology have been discovered more recently for CRT, as well as its role as a dominant 'eat-me' prophagocytic signal. Intriguingly, cell-surface exposure/secretion of CRT is among the infective strategies used by parasites such as Trypanosoma cruzi , Entamoeba histolytica , Taenia solium , Leishmania donovani and Schistosoma mansoni . Because of the inherent flexibility of CRTs, their analysis by X-ray crystallography requires the design of recombinant constructs suitable for crystallization, and thus only the structures of two very similar mammalian CRT lectin domains are known. With the X-ray structures of two distant parasite CRTs, insights into species structural determinants that might be harnessed to fight against the parasites without affecting the functions of the host CRT are now provided. Moreover, although the hypothesis that CRT can exhibit both open and closed conformations has been proposed in relation to its chaperone function, only the open conformation has so far been observed in crystal structures. The first evidence is now provided of a complex conformational transition with the junction reoriented towards P-domain closure. SAXS experiments also provided additional information about the flexibility of T. cruzi CRT in solution, thus complementing crystallographic data on the open conformation. Finally, regarding the conserved lectin-domain structure and chaperone function, evidence is provided of its dual carbohydrate/protein specificity and a new scheme is proposed to interpret such unusual substrate-binding properties. These fascinating features are fully consistent with previous experimental observations, as discussed considering the broad spectrum of CRT sequence conservations and differences.

  2. Structures of parasite calreticulins provide insights into their flexibility and dual carbohydrate/peptide-binding properties

    Directory of Open Access Journals (Sweden)

    Christophe Moreau

    2016-11-01

    Full Text Available Calreticulin (CRT is a multifaceted protein, initially discovered as an endoplasmic reticulum (ER chaperone protein, that is essential in calcium metabolism. Various implications in cancer, early development and immunology have been discovered more recently for CRT, as well as its role as a dominant `eat-me' prophagocytic signal. Intriguingly, cell-surface exposure/secretion of CRT is among the infective strategies used by parasites such as Trypanosoma cruzi, Entamoeba histolytica, Taenia solium, Leishmania donovani and Schistosoma mansoni. Because of the inherent flexibility of CRTs, their analysis by X-ray crystallography requires the design of recombinant constructs suitable for crystallization, and thus only the structures of two very similar mammalian CRT lectin domains are known. With the X-ray structures of two distant parasite CRTs, insights into species structural determinants that might be harnessed to fight against the parasites without affecting the functions of the host CRT are now provided. Moreover, although the hypothesis that CRT can exhibit both open and closed conformations has been proposed in relation to its chaperone function, only the open conformation has so far been observed in crystal structures. The first evidence is now provided of a complex conformational transition with the junction reoriented towards P-domain closure. SAXS experiments also provided additional information about the flexibility of T. cruzi CRT in solution, thus complementing crystallographic data on the open conformation. Finally, regarding the conserved lectin-domain structure and chaperone function, evidence is provided of its dual carbohydrate/protein specificity and a new scheme is proposed to interpret such unusual substrate-binding properties. These fascinating features are fully consistent with previous experimental observations, as discussed considering the broad spectrum of CRT sequence conservations and differences.

  3. A molecular dynamics investigation of CDK8/CycC and ligand binding: conformational flexibility and implication in drug discovery

    Science.gov (United States)

    Cholko, Timothy; Chen, Wei; Tang, Zhiye; Chang, Chia-en A.

    2018-05-01

    Abnormal activity of cyclin-dependent kinase 8 (CDK8) along with its partner protein cyclin C (CycC) is a common feature of many diseases including colorectal cancer. Using molecular dynamics (MD) simulations, this study determined the dynamics of the CDK8-CycC system and we obtained detailed breakdowns of binding energy contributions for four type-I and five type-II CDK8 inhibitors. We revealed system motions and conformational changes that will affect ligand binding, confirmed the essentialness of CycC for inclusion in future computational studies, and provide guidance in development of CDK8 binders. We employed unbiased all-atom MD simulations for 500 ns on twelve CDK8-CycC systems, including apoproteins and protein-ligand complexes, then performed principal component analysis (PCA) and measured the RMSF of key regions to identify protein dynamics. Binding pocket volume analysis identified conformational changes that accompany ligand binding. Next, H-bond analysis, residue-wise interaction calculations, and MM/PBSA were performed to characterize protein-ligand interactions and find the binding energy. We discovered that CycC is vital for maintaining a proper conformation of CDK8 to facilitate ligand binding and that the system exhibits motion that should be carefully considered in future computational work. Surprisingly, we found that motion of the activation loop did not affect ligand binding. Type-I and type-II ligand binding is driven by van der Waals interactions, but electrostatic energy and entropic penalties affect type-II binding as well. Binding of both ligand types affects protein flexibility. Based on this we provide suggestions for development of tighter-binding CDK8 inhibitors and offer insight that can aid future computational studies.

  4. The thermodynamic signature of ligand binding to histone deacetylase-like amidohydrolases is most sensitive to the flexibility in the L2-loop lining the active site pocket.

    Science.gov (United States)

    Meyners, Christian; Krämer, Andreas; Yildiz, Özkan; Meyer-Almes, Franz-Josef

    2017-07-01

    The analysis of the thermodynamic driving forces of ligand-protein binding has been suggested to be a key component for the selection and optimization of active compounds into drug candidates. The binding enthalpy as deduced from isothermal titration calorimetry (ITC) is usually interpreted assuming single-step binding of a ligand to one conformation of the target protein. Although successful in many cases, these assumptions are oversimplified approximations of the reality with flexible proteins and complicated binding mechanism in many if not most cases. The relationship between protein flexibility and thermodynamic signature of ligand binding is largely understudied. Directed mutagenesis, X-ray crystallography, enzyme kinetics and ITC methods were combined to dissect the influence of loop flexibility on the thermodynamics and mechanism of ligand binding to histone deacetylase (HDAC)-like amidohydrolases. The general ligand-protein binding mechanism comprises an energetically demanding gate opening step followed by physical binding. Increased flexibility of the L2-loop in HDAC-like amidohydrolases facilitates access of ligands to the binding pocket resulting in predominantly enthalpy-driven complex formation. The study provides evidence for the great importance of flexibility adjacent to the active site channel for the mechanism and observed thermodynamic driving forces of molecular recognition in HDAC like enzymes. The flexibility or malleability in regions adjacent to binding pockets should be given more attention when designing better drug candidates. The presented case study also suggests that the observed binding enthalpy of protein-ligand systems should be interpreted with caution, since more complicated binding mechanisms may obscure the significance regarding potential drug likeness. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. A Flexible Binding Site Architecture Provides New Insights into CcpA Global Regulation in Gram-Positive Bacteria.

    Science.gov (United States)

    Yang, Yunpeng; Zhang, Lu; Huang, He; Yang, Chen; Yang, Sheng; Gu, Yang; Jiang, Weihong

    2017-01-24

    Catabolite control protein A (CcpA) is the master regulator in Gram-positive bacteria that mediates carbon catabolite repression (CCR) and carbon catabolite activation (CCA), two fundamental regulatory mechanisms that enable competitive advantages in carbon catabolism. It is generally regarded that CcpA exerts its regulatory role by binding to a typical 14- to 16-nucleotide (nt) consensus site that is called a catabolite response element (cre) within the target regions. However, here we report a previously unknown noncanonical flexible architecture of the CcpA-binding site in solventogenic clostridia, providing new mechanistic insights into catabolite regulation. This novel CcpA-binding site, named cre var , has a unique architecture that consists of two inverted repeats and an intervening spacer, all of which are variable in nucleotide composition and length, except for a 6-bp core palindromic sequence (TGTAAA/TTTACA). It was found that the length of the intervening spacer of cre var can affect CcpA binding affinity, and moreover, the core palindromic sequence of cre var is the key structure for regulation. Such a variable architecture of cre var shows potential importance for CcpA's diverse and fine regulation. A total of 103 potential cre var sites were discovered in solventogenic Clostridium acetobutylicum, of which 42 sites were picked out for electrophoretic mobility shift assays (EMSAs), and 30 sites were confirmed to be bound by CcpA. These 30 cre var sites are associated with 27 genes involved in many important pathways. Also of significance, the cre var sites are found to be widespread and function in a great number of taxonomically different Gram-positive bacteria, including pathogens, suggesting their global role in Gram-positive bacteria. In Gram-positive bacteria, the global regulator CcpA controls a large number of important physiological and metabolic processes. Although a typical consensus CcpA-binding site, cre, has been identified, it remains

  6. A matrix-focused structure-activity and binding site flexibility study of quinolinol inhibitors of botulinum neurotoxin serotype A.

    Science.gov (United States)

    Harrell, William A; Vieira, Rebecca C; Ensel, Susan M; Montgomery, Vicki; Guernieri, Rebecca; Eccard, Vanessa S; Campbell, Yvette; Roxas-Duncan, Virginia; Cardellina, John H; Webb, Robert P; Smith, Leonard A

    2017-02-01

    Our initial discovery of 8-hydroxyquinoline inhibitors of BoNT/A and separation/testing of enantiomers of one of the more active leads indicated considerable flexibility in the binding site. We designed a limited study to investigate this flexibility and probe structure-activity relationships; utilizing the Betti reaction, a 36 compound matrix of quinolinol BoNT/A LC inhibitors was developed using three 8-hydroxyquinolines, three heteroaromatic amines, and four substituted benzaldehydes. This study has revealed some of the most effective quinolinol-based BoNT/A inhibitors to date, with 7 compounds displaying IC 50 values ⩽1μM and 11 effective at ⩽2μM in an ex vivo assay. Published by Elsevier Ltd.

  7. Novel Bacterial Topoisomerase Inhibitors Exploit Asp83 and the Intrinsic Flexibility of the DNA Gyrase Binding Site

    Directory of Open Access Journals (Sweden)

    Sebastian Franco-Ulloa

    2018-02-01

    Full Text Available DNA gyrases are enzymes that control the topology of DNA in bacteria cells. This is a vital function for bacteria. For this reason, DNA gyrases are targeted by widely used antibiotics such as quinolones. Recently, structural and biochemical investigations identified a new class of DNA gyrase inhibitors called NBTIs (i.e., novel bacterial topoisomerase inhibitors. NBTIs are particularly promising because they are active against multi-drug resistant bacteria, an alarming clinical issue. Structural data recently demonstrated that these NBTIs bind tightly to a newly identified pocket at the dimer interface of the DNA–protein complex. In the present study, we used molecular dynamics (MD simulations and docking calculations to shed new light on the binding of NBTIs to this site. Interestingly, our MD simulations demonstrate the intrinsic flexibility of this binding site, which allows the pocket to adapt its conformation and form optimal interactions with the ligand. In particular, we examined two ligands, AM8085 and AM8191, which induced a repositioning of a key aspartate (Asp83B, whose side chain can rotate within the binding site. The conformational rearrangement of Asp83B allows the formation of a newly identified H-bond interaction with an NH on the bound NBTI, which seems important for the binding of NBTIs having such functionality. We validated these findings through docking calculations using an extended set of cognate oxabicyclooctane-linked NBTIs derivatives (~150, in total, screened against multiple target conformations. The newly identified H-bond interaction significantly improves the docking enrichment. These insights could be helpful for future virtual screening campaigns against DNA gyrase.

  8. A Flexible Binding Site Architecture Provides New Insights into CcpA Global Regulation in Gram-Positive Bacteria

    Directory of Open Access Journals (Sweden)

    Yunpeng Yang

    2017-01-01

    Full Text Available Catabolite control protein A (CcpA is the master regulator in Gram-positive bacteria that mediates carbon catabolite repression (CCR and carbon catabolite activation (CCA, two fundamental regulatory mechanisms that enable competitive advantages in carbon catabolism. It is generally regarded that CcpA exerts its regulatory role by binding to a typical 14- to 16-nucleotide (nt consensus site that is called a catabolite response element (cre within the target regions. However, here we report a previously unknown noncanonical flexible architecture of the CcpA-binding site in solventogenic clostridia, providing new mechanistic insights into catabolite regulation. This novel CcpA-binding site, named crevar, has a unique architecture that consists of two inverted repeats and an intervening spacer, all of which are variable in nucleotide composition and length, except for a 6-bp core palindromic sequence (TGTAAA/TTTACA. It was found that the length of the intervening spacer of crevar can affect CcpA binding affinity, and moreover, the core palindromic sequence of crevar is the key structure for regulation. Such a variable architecture of crevar shows potential importance for CcpA’s diverse and fine regulation. A total of 103 potential crevar sites were discovered in solventogenic Clostridium acetobutylicum, of which 42 sites were picked out for electrophoretic mobility shift assays (EMSAs, and 30 sites were confirmed to be bound by CcpA. These 30 crevar sites are associated with 27 genes involved in many important pathways. Also of significance, the crevar sites are found to be widespread and function in a great number of taxonomically different Gram-positive bacteria, including pathogens, suggesting their global role in Gram-positive bacteria.

  9. The flexible C-terminal arm of the Lassa arenavirus Z-protein mediates interactions with multiple binding partners.

    Science.gov (United States)

    May, Eric R; Armen, Roger S; Mannan, Aristotle M; Brooks, Charles L

    2010-08-01

    The arenavirus genome encodes for a Z-protein, which contains a RING domain that coordinates two zinc ions, and has been identified as having several functional roles at various stages of the virus life cycle. Z-protein binds to multiple host proteins and has been directly implicated in the promotion of viral budding, repression of mRNA translation, and apoptosis of infected cells. Using homology models of the Z-protein from Lassa strain arenavirus, replica exchange molecular dynamics (MD) was used to refine the structures, which were then subsequently clustered. Population-weighted ensembles of low-energy cluster representatives were predicted based upon optimal agreement of the chemical shifts computed with the SPARTA program with the experimental NMR chemical shifts. A member of the refined ensemble was identified to be a potential binder of budding factor Tsg101 based on its correspondence to the structure of the HIV-1 Gag late domain when bound to Tsg101. Members of these ensembles were docked against the crystal structure of human eIF4E translation initiation factor. Two plausible binding modes emerged based upon their agreement with experimental observation, favorable interaction energies and stability during MD trajectories. Mutations to Z are proposed that would either inhibit both binding mechanisms or selectively inhibit only one mode. The C-terminal domain conformation of the most populated member of the representative ensemble shielded protein-binding recognition motifs for Tsg101 and eIF4E and represents the most populated state free in solution. We propose that C-terminal flexibility is key for mediating the different functional states of the Z-protein. (c) 2010 Wiley-Liss, Inc.

  10. Antimicrobial Peptide Potency is Facilitated by Greater Conformational Flexibility when Binding to Gram-negative Bacterial Inner Membranes

    Science.gov (United States)

    Amos, Sarah-Beth T. A.; Vermeer, Louic S.; Ferguson, Philip M.; Kozlowska, Justyna; Davy, Matthew; Bui, Tam T.; Drake, Alex F.; Lorenz, Christian D.; Mason, A. James

    2016-11-01

    The interaction of antimicrobial peptides (AMPs) with the inner membrane of Gram-negative bacteria is a key determinant of their abilities to exert diverse bactericidal effects. Here we present a molecular level understanding of the initial target membrane interaction for two cationic α-helical AMPs that share structural similarities but have a ten-fold difference in antibacterial potency towards Gram-negative bacteria. The binding and insertion from solution of pleurocidin or magainin 2 to membranes representing the inner membrane of Gram-negative bacteria, comprising a mixture of 128 anionic and 384 zwitterionic lipids, is monitored over 100 ns in all atom molecular dynamics simulations. The effects of the membrane interaction on both the peptide and lipid constituents are considered and compared with new and published experimental data obtained in the steady state. While both magainin 2 and pleurocidin are capable of disrupting bacterial membranes, the greater potency of pleurocidin is linked to its ability to penetrate within the bacterial cell. We show that pleurocidin displays much greater conformational flexibility when compared with magainin 2, resists self-association at the membrane surface and penetrates further into the hydrophobic core of the lipid bilayer. Conformational flexibility is therefore revealed as a key feature required of apparently α-helical cationic AMPs for enhanced antibacterial potency.

  11. Evidence supporting a role for astrocytes in the regulation of cognitive flexibility and neuronal oscillations through the Ca2+ binding protein S100β.

    Science.gov (United States)

    Brockett, Adam T; Kane, Gary A; Monari, Patrick K; Briones, Brandy A; Vigneron, Pierre-Antoine; Barber, Gabriela A; Bermudez, Andres; Dieffenbach, Uma; Kloth, Alexander D; Buschman, Timothy J; Gould, Elizabeth

    2018-01-01

    The medial prefrontal cortex (mPFC) is important for cognitive flexibility, the ability to switch between two task-relevant dimensions. Changes in neuronal oscillations and alterations in the coupling across frequency ranges have been correlated with attention and cognitive flexibility. Here we show that astrocytes in the mPFC of adult male Sprague Dawley rats, participate in cognitive flexibility through the astrocyte-specific Ca2+ binding protein S100β, which improves cognitive flexibility and increases phase amplitude coupling between theta and gamma oscillations. We further show that reduction of astrocyte number in the mPFC impairs cognitive flexibility and diminishes delta, alpha and gamma power. Conversely, chemogenetic activation of astrocytic intracellular Ca2+ signaling in the mPFC enhances cognitive flexibility, while inactivation of endogenous S100β among chemogenetically activated astrocytes in the mPFC prevents this improvement. Collectively, our work suggests that astrocytes make important contributions to cognitive flexibility and that they do so by releasing a Ca2+ binding protein which in turn enhances coordinated neuronal oscillations.

  12. Protein flexibility and ligand rigidity : a thermodynamic and kinetic study of ITAM-based ligand binding to Syk tandem SH2

    NARCIS (Netherlands)

    de Mol, Nico J; Catalina, M Isabel; Dekker, Frank J; Fischer, Marcel J E; Heck, Albert J R; Liskamp, Rob M J; Dekker, Frank

    2005-01-01

    The Syk tandem Src homology 2 domain (Syk tSH2) constitutes a flexible protein module involved in the regulation of Syk kinase activity. The Syk tSH2 domain is assumed to function by adapting the distance between its two SH2 domains upon bivalent binding to diphosphotyrosine ligands. A thermodynamic

  13. 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.

  14. 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

  15. 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.

  16. 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

  17. Selective binding of pyrene in subdomain IB of human serum albumin: Combining energy transfer spectroscopy and molecular modelling to understand protein binding flexibility

    Science.gov (United States)

    Ling, Irene; Taha, Mohamed; Al-Sharji, Nada A.; Abou-Zied, Osama K.

    2018-04-01

    The ability of human serum albumin (HSA) to bind medium-sized hydrophobic molecules is important for the distribution, metabolism, and efficacy of many drugs. Herein, the interaction between pyrene, a hydrophobic fluorescent probe, and HSA was thoroughly investigated using steady-state and time-resolved fluorescence techniques, ligand docking, and molecular dynamics (MD) simulations. A slight quenching of the fluorescence signal from Trp214 (the sole tryptophan residue in the protein) in the presence of pyrene was used to determine the ligand binding site in the protein, using Förster's resonance energy transfer (FRET) theory. The estimated FRET apparent distance between pyrene and Trp214 was 27 Å, which was closely reproduced by the docking analysis (29 Å) and MD simulation (32 Å). The highest affinity site for pyrene was found to be in subdomain IB from the docking results. The calculated equilibrium structure of the complex using MD simulation shows that the ligand is largely stabilized by hydrophobic interaction with Phe165, Phe127, and the nonpolar moieties of Tyr138 and Tyr161. The fluorescence vibronic peak ratio I1/I3 of bound pyrene inside HSA indicates the presence of polar effect in the local environment of pyrene which is less than that of free pyrene in buffer. This was clarified by the MD simulation results in which an average of 5.7 water molecules were found within 0.5 nm of pyrene in the binding site. Comparing the fluorescence signals and lifetimes of pyrene inside HSA to that free in buffer, the high tendency of pyrene to form dimer was almost completely suppressed inside HSA, indicating a high selectivity of the binding pocket toward pyrene monomer. The current results emphasize the ability of HSA, as a major carrier of several drugs and ligands in blood, to bind hydrophobic molecules in cavities other than subdomain IIA which is known to bind most hydrophobic drugs. This ability stems from the nature of the amino acids forming the binding

  18. Ribosomal protein L5 has a highly twisted concave surface and flexible arms responsible for rRNA binding.

    Science.gov (United States)

    Nakashima, T; Yao, M; Kawamura, S; Iwasaki, K; Kimura, M; Tanaka, I

    2001-05-01

    Ribosomal protein L5 is a 5S rRNA binding protein in the large subunit and plays an essential role in the promotion of a particular conformation of 5S rRNA. The crystal structure of the ribosomal protein L5 from Bacillus stearothermophilus has been determined at 1.8 A resolution. The molecule consists of a five-stranded antiparallel beta-sheet and four alpha-helices, which fold in a way that is topologically similar to the ribonucleoprotein (RNP) domain. The molecular shape and electrostatic representation suggest that the concave surface and loop regions are involved in 5S rRNA binding. To identify amino acid residues responsible for 5S rRNA binding, we made use of Ala-scanning mutagenesis of evolutionarily conserved amino acids occurring in the beta-strands and loop regions. The mutations of Asn37 at the beta1-strand and Gln63 at the loop between helix 2 and beta3-strand as well as that of Phe77 at the tip of the loop structure between the beta2- and beta3-strands caused a significant reduction in 5S rRNA binding. In addition, the mutations of Thr90 on the beta3-strand and Ile141 and Asp144 at the loop between beta4- and beta5-strands moderately reduced the 5S rRNA-binding affinity. Comparison of these results with the more recently analyzed structure of the 50S subunit from Haloarcula marismortui suggests that there are significant differences in the structure at N- and C-terminal regions and probably in the 5S rRNA binding.

  19. Ribosomal protein L5 has a highly twisted concave surface and flexible arms responsible for rRNA binding.

    OpenAIRE

    Nakashima, T; Yao, M; Kawamura, S; Iwasaki, K; Kimura, M; Tanaka, I

    2001-01-01

    Ribosomal protein L5 is a 5S rRNA binding protein in the large subunit and plays an essential role in the promotion of a particular conformation of 5S rRNA. The crystal structure of the ribosomal protein L5 from Bacillus stearothermophilus has been determined at 1.8 A resolution. The molecule consists of a five-stranded antiparallel beta-sheet and four alpha-helices, which fold in a way that is topologically similar to the ribonucleoprotein (RNP) domain. The molecular shape and electrostatic ...

  20. Novel binding motif and new flexibility revealed by structural analyses of a pyruvate dehydrogenase-dihydrolipoyl acetyltransferase subcomplex from the Escherichia coli pyruvate dehydrogenase multienzyme complex.

    Science.gov (United States)

    Arjunan, Palaniappa; Wang, Junjie; Nemeria, Natalia S; Reynolds, Shelley; Brown, Ian; Chandrasekhar, Krishnamoorthy; Calero, Guillermo; Jordan, Frank; Furey, William

    2014-10-24

    The Escherichia coli pyruvate dehydrogenase multienzyme complex contains multiple copies of three enzymatic components, E1p, E2p, and E3, that sequentially carry out distinct steps in the overall reaction converting pyruvate to acetyl-CoA. Efficient functioning requires the enzymatic components to assemble into a large complex, the integrity of which is maintained by tethering of the displaced, peripheral E1p and E3 components to the E2p core through non-covalent binding. We here report the crystal structure of a subcomplex between E1p and an E2p didomain containing a hybrid lipoyl domain along with the peripheral subunit-binding domain responsible for tethering to the core. In the structure, a region at the N terminus of each subunit in the E1p homodimer previously unseen due to crystallographic disorder was observed, revealing a new folding motif involved in E1p-E2p didomain interactions, and an additional, unexpected, flexibility was discovered in the E1p-E2p didomain subcomplex, both of which probably have consequences in the overall multienzyme complex assembly. This represents the first structure of an E1p-E2p didomain subcomplex involving a homodimeric E1p, and the results may be applicable to a large range of complexes with homodimeric E1 components. Results of HD exchange mass spectrometric experiments using the intact, wild type 3-lipoyl E2p and E1p are consistent with the crystallographic data obtained from the E1p-E2p didomain subcomplex as well as with other biochemical and NMR data reported from our groups, confirming that our findings are applicable to the entire E1p-E2p assembly. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. Novel Binding Motif and New Flexibility Revealed by Structural Analyses of a Pyruvate Dehydrogenase-Dihydrolipoyl Acetyltransferase Subcomplex from the Escherichia coli Pyruvate Dehydrogenase Multienzyme Complex*

    Science.gov (United States)

    Arjunan, Palaniappa; Wang, Junjie; Nemeria, Natalia S.; Reynolds, Shelley; Brown, Ian; Chandrasekhar, Krishnamoorthy; Calero, Guillermo; Jordan, Frank; Furey, William

    2014-01-01

    The Escherichia coli pyruvate dehydrogenase multienzyme complex contains multiple copies of three enzymatic components, E1p, E2p, and E3, that sequentially carry out distinct steps in the overall reaction converting pyruvate to acetyl-CoA. Efficient functioning requires the enzymatic components to assemble into a large complex, the integrity of which is maintained by tethering of the displaced, peripheral E1p and E3 components to the E2p core through non-covalent binding. We here report the crystal structure of a subcomplex between E1p and an E2p didomain containing a hybrid lipoyl domain along with the peripheral subunit-binding domain responsible for tethering to the core. In the structure, a region at the N terminus of each subunit in the E1p homodimer previously unseen due to crystallographic disorder was observed, revealing a new folding motif involved in E1p-E2p didomain interactions, and an additional, unexpected, flexibility was discovered in the E1p-E2p didomain subcomplex, both of which probably have consequences in the overall multienzyme complex assembly. This represents the first structure of an E1p-E2p didomain subcomplex involving a homodimeric E1p, and the results may be applicable to a large range of complexes with homodimeric E1 components. Results of HD exchange mass spectrometric experiments using the intact, wild type 3-lipoyl E2p and E1p are consistent with the crystallographic data obtained from the E1p-E2p didomain subcomplex as well as with other biochemical and NMR data reported from our groups, confirming that our findings are applicable to the entire E1p-E2p assembly. PMID:25210042

  2. Evaluation of simultaneous binding of Chromomycin A3 to the multiple sites of DNA by the new restriction enzyme assay.

    Science.gov (United States)

    Murase, Hirotaka; Noguchi, Tomoharu; Sasaki, Shigeki

    2018-06-01

    Chromomycin A3 (CMA3) is an aureolic acid-type antitumor antibiotic. CMA3 forms dimeric complexes with divalent cations, such as Mg 2+ , which strongly binds to the GC rich sequence of DNA to inhibit DNA replication and transcription. In this study, the binding property of CMA3 to the DNA sequence containing multiple GC-rich binding sites was investigated by measuring the protection from hydrolysis by the restriction enzymes, AccII and Fnu4HI, for the center of the CGCG site and the 5'-GC↓GGC site, respectively. In contrast to the standard DNase I footprinting method, the DNA substrates are fully hydrolyzed by the restriction enzymes, therefore, the full protection of DNA at all the cleavable sites indicates that CMA3 simultaneously binds to all the binding sites. The restriction enzyme assay has suggested that CMA3 has a high tendency to bind the successive CGCG sites and the CGG repeat. Copyright © 2018 Elsevier Ltd. All rights reserved.

  3. Human T-cell leukemia virus type 1 Tax requires direct access to DNA for recruitment of CREB binding protein to the viral promoter.

    Science.gov (United States)

    Lenzmeier, B A; Giebler, H A; Nyborg, J K

    1998-02-01

    Efficient human T-cell leukemia virus type 1 (HTLV-1) replication and viral gene expression are dependent upon the virally encoded oncoprotein Tax. To activate HTLV-1 transcription, Tax interacts with the cellular DNA binding protein cyclic AMP-responsive element binding protein (CREB) and recruits the coactivator CREB binding protein (CBP), forming a nucleoprotein complex on the three viral cyclic AMP-responsive elements (CREs) in the HTLV-1 promoter. Short stretches of dG-dC-rich (GC-rich) DNA, immediately flanking each of the viral CREs, are essential for Tax recruitment of CBP in vitro and Tax transactivation in vivo. Although the importance of the viral CRE-flanking sequences is well established, several studies have failed to identify an interaction between Tax and the DNA. The mechanistic role of the viral CRE-flanking sequences has therefore remained enigmatic. In this study, we used high resolution methidiumpropyl-EDTA iron(II) footprinting to show that Tax extended the CREB footprint into the GC-rich DNA flanking sequences of the viral CRE. The Tax-CREB footprint was enhanced but not extended by the KIX domain of CBP, suggesting that the coactivator increased the stability of the nucleoprotein complex. Conversely, the footprint pattern of CREB on a cellular CRE lacking GC-rich flanking sequences did not change in the presence of Tax or Tax plus KIX. The minor-groove DNA binding drug chromomycin A3 bound to the GC-rich flanking sequences and inhibited the association of Tax and the Tax-CBP complex without affecting CREB binding. Tax specifically cross-linked to the viral CRE in the 5'-flanking sequence, and this cross-link was blocked by chromomycin A3. Together, these data support a model where Tax interacts directly with both CREB and the minor-groove viral CRE-flanking sequences to form a high-affinity binding site for the recruitment of CBP to the HTLV-1 promoter.

  4. Flexible Bronchoscopy.

    Science.gov (United States)

    Miller, Russell J; Casal, Roberto F; Lazarus, Donald R; Ost, David E; Eapen, George A

    2018-03-01

    Flexible bronchoscopy has changed the course of pulmonary medicine. As technology advances, the role of the flexible bronchoscope for both diagnostic and therapeutic indications is continually expanding. This article reviews the historical development of the flexible bronchoscopy, fundamental uses of the flexible bronchoscope as a tool to examine the central airways and obtain diagnostic tissue, and the indications, complications, and contraindications to flexible bronchoscopy. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Functional aspects of protein flexibility

    DEFF Research Database (Denmark)

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

    2009-01-01

    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...

  6. On flexibility

    OpenAIRE

    Weiss, Christoph R.; 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...

  7. One-Step Interface Engineering for All-Inkjet-Printed, All-Organic Components in Transparent, Flexible Transistors and Inverters: Polymer Binding.

    Science.gov (United States)

    Ha, Jewook; Chung, Seungjun; Pei, Mingyuan; Cho, Kilwon; Yang, Hoichang; Hong, Yongtaek

    2017-03-15

    We report a one-step interface engineering methodology which can be used on both polymer electrodes and gate dielectric for all-inkjet-printed, flexible, transparent organic thin-film transistors (OTFTs) and inverters. Dimethylchlorosilane-terminated polystyrene (PS) was introduced as a surface modifier to cured poly(4-vinylphenol) dielectric and poly(3,4-ethylenedioxythiophene):polystyrenesulfonate (PEDOT:PSS) electrodes without any pretreatment. On the untreated and PS interlayer-treated dielectric and electrode surfaces, 6,13-bis(triisopropylsilylethynyl)pentacene was printed to fabricate OTFTs and inverters. With the benefit of the PS interlayer, the electrical properties of the OTFTs on a flexible plastic substrate were significantly improved, as shown by a field-effect mobility (μ FET ) of 0.27 cm 2  V -1  s -1 and an on/off current ratio (I on /I off ) of greater than 10 6 . In contrast, the untreated systems showed a low μ FET of less than 0.02 cm 2  V -1  s -1 and I on /I off ∼ 10 4 . Additionally, the all-inkjet-printed inverters based on the PS-modified surfaces exhibited a voltage gain of 7.17 V V -1 . The all-organic-based TFTs and inverters, including deformable and transparent PEDOT:PSS electrodes with a sheet resistance of 160-250 Ω sq -1 , exhibited a light transmittance of higher than 70% (at wavelength of 550 nm). Specifically, there was no significant degradation in the electrical performance of the interface engineering-assisted system after 1000 bending cycles at a radius of 5 mm.

  8. 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.

  9. 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)

    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

  10. Differential modulation of binding loop flexibility and stability by Arg50 and Arg52 in Cucurbita maxima trypsin inhibitor-V deduced by trypsin-catalyzed hydrolysis and NMR spectroscopy.

    Science.gov (United States)

    Cai, M; Huang, Y; Prakash, O; Wen, L; Dunkelbarger, S P; Huang, J K; Liu, J; Krishnamoorthi, R

    1996-04-16

    The side chains of Arg50 and Arg52 iin Cucurbita maxima trypsin inhibitor-V (CMTI-V) anchor the binding loop to the scaffold region [Cai, M., Gong, Y., Kao, J.L-F., & Krishnamoorthi, R. (1995) Biochemistry 34, 5201-5211]. The consequences of these hydrogen-bonding and electrostatic interactions on the conformational flexibility and stability of the binding loop were evaluated by trypsin-catalyzed hydrolysis of CMTI-V mutants, in which each of the arginines was individually replaced with Ala, Lys, or Gln by genetic engineering methods. All mutants exhibited significantly increased vulnerability to the protease attack at many sites, including the reactive-site (Lys44-Asp45 peptide bond), with the R50 mutants showing much more pronounced effects than the R52 counterparts. For CmTI-V and the mutants studied, a qualitative correlation was inferred between binding loop flexibility and retention time on a reverse-phase high-pressure liquid chromatography C-18 column. The R50 mutants were found to be more flexible than the corresponding R52 versions. These results demonstrate that Arg50 contributes more to the stability and function of CMTI-V. The differing strengths of the hydrogen bonds made by Arg50 and Arg52 were characterized by determining the internal dynamics of their side chains at pH 5.0 and 2.5: 15N NMR longitudinal and transverse relaxation rates and 15N-1H nuclear Overhauser effect (NOE) enhancements were measured for the main-chain and side-chain NH groups in 15N-labeled recombinant CMTI-V (rCMTI-V) and the model-free parameters [Lipari, G., & Szabo, A.(1982) J. Am. Chem. Soc. 104, 4546-59; 4559-4570] were calculated. At both pH 5.0 and 2.5, the arginines at positions 26, 47, 58 and 66 are found to be highly mobile, as the caluculated general order parameters, S2 values, of their NepsilonH groups fall in the range 0.03-0.18. The corresponding values for Arg50 amd Arg52 are 0.73 and 0.63, respectively, at pH 5.0, thus confirming that the two arginines are

  11. 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)].

  12. 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

  13. Workplace flexibility.

    Science.gov (United States)

    Scordato, C; Harris, J

    1990-01-01

    Whether your organization is in a growth pattern or downsizing, you are probably facing change. To gain some insight into your options, here is an in-depth look at the problems and benefits of some flexible work arrangements from a just published study by Catalyst.

  14. Flexibility conflict?

    NARCIS (Netherlands)

    Delsen, L.W.M.; Bauer, F.; Groß, H.; Sieglen, G.

    2002-01-01

    The chapter deals with the presupposed conflict of interests between employers and employees resulting from a decoupling of operating hours and working times. It starts from the notion that both long operating hours and flexibility are relative concepts. As there is some discretion, the ultimate

  15. Flexible licensing

    Directory of Open Access Journals (Sweden)

    Martyn Jansen

    2012-07-01

    Full Text Available The case is presented for a more flexible approach to licensing online library resources. Today's distributed education environment creates pressure for UK higher and further education institutions (HEI/FEIs to form partnerships and to develop educational products and roll them out across the globe. Online library resources are a key component of distributed education and yet existing licensing agreements struggle to keep pace with the increasing range of users and purposes for which they are required. This article describes the process of developing a flexible approach to licensing and proposes a new model licence for online library resources which has the adaptability needed in this new global educational landscape. These ideas have been presented and discussed at various workshops across Eduserv's and JISC Collections' higher education and publisher communities, and further consultation is ongoing.

  16. Flexibility of the myosin heavy chain: direct evidence that the region containing SH/sub 1/ and SH/sub 2/ can move 10 /Angstrom/ under the influence of nucleotide binding

    Energy Technology Data Exchange (ETDEWEB)

    Huston, E.E.; Grammer, J.C.; Yount, R.G.

    1988-12-13

    Previous experiments demonstrated that two thiols of skeletal myosin subfragment 1 (SF/sub 1/) could be oxidized to a disulfide bond by treatment with a 2-fold excess of 5,5'-dithiobis (2-nitrobenzoic acid) (DTNB) in the presence of MgADP. The resulting characteristic changes in the ATPase activities of SF/sub 1/ and the fact that MgADP was stably trapped at the active site, suggested that the two thiols cross-linked were SH/sub 1/ (Cys-707) and SH/sub 2/ (Cys-697) from the myosin heavy chain. To verify this suggestion, SF/sub 1/, after DTNB treatment as above, was treated with an excess of N-ethylmaleimide to block all accessible thiols. The single protein disulfide produced by DTNB oxidation was reduced with dithioerythritol and the modified SF/sub 1/ internally cross-linked with equimolar (/sup 14/C)p-phenylenedimaleimide (pPDM) in the presence of MgADP. After extensive trypsinization, the major /sup 14/C-labeled peptide was isolated, characterized, and shown to be Cys-Asn-Gly-Val-Leu-Gly-Ile-Arg-Ile-Cys-Arg, in which the two cysteines were cross-linked by pPDM. This peptide is known to contain SH/sub 2/ and SH/sub 1/ in this order and to come from residues 697-708 in the rabbit skeletal myosin heavy chain. Parallel experiments with (/sup 14/C)pPDM and unmodified SF/sub 1/ similar to those above gave an identical SH/sub 1/, SH/sub 2/ tryptic peptide, verifying earlier labeling results. These combined results demonstrate that SH/sub 1/ and SH/sub 2/ cross-linked by pPDM (12-13 /Angstrom/, S to S) or by oxidation with DTNB (2 /Angstrom/, S to S) can move a minimum of 10 /Angstrom/ under the influence of nucleotide binding. Because these residues are separated by only nine amino acids in the primary sequence, this small section of the heavy chain must possess extraordinary flexibility.

  17. Flexible Consumption

    DEFF Research Database (Denmark)

    Holm Jacobsen, Peter; Pallesen, Trine

    This report presents the first findings from our qualitative study of consumer behaviour vis-à-vis flexible consumption. The main of objective of this report is to present our first round of data from Bornholm, and to assist the design of products/services designed in WP6. In the report, we adopt...... the perspective of the consumer: what does living in a demand response setup look like to participants – and what kinds of behaviour and interest motivate – and emerge from – their participation in EcoGrid 2.0....

  18. Flexible Capitalism

    DEFF Research Database (Denmark)

    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...... 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...

  19. Flexible nanovectors

    International Nuclear Information System (INIS)

    Pugno, Nicola M

    2008-01-01

    In this paper we show that the control of adhesion in highly flexible (a property that could be crucial for smart drug delivery but which is still ignored in the literature) nanovectors can help in smartly targeting and delivering the drug. The existence of and the conditions for activating and controlling a super-adhesive state are addressed. Even if such a state has never been observed in nanovectors, our calculations, as well as observations in spiders and geckos, suggest its existence and feasible control. Control of the competition between the drag and the adhesive force is exploited to improve the targeting ability and a hierarchical model is applied to describe a real vasculature. The high flexibility of the nanovector is used to smartly deliver the drug only during adhesion by nanopumping or, as a limiting case, by the new concept of 'adhesion induced nanovector implosion'; a liquid drop analogy is utilized for the calculations. Fast (pumping) and slow (diffusion) drug deliveries can thus be separately controlled by controlling the size and shape of the nanovector. Multiple stage nanovectors are also briefly discussed, mimicking aerospace vector strategies.

  20. Flexible nanovectors

    Science.gov (United States)

    Pugno, Nicola M.

    2008-11-01

    In this paper we show that the control of adhesion in highly flexible (a property that could be crucial for smart drug delivery but which is still ignored in the literature) nanovectors can help in smartly targeting and delivering the drug. The existence of and the conditions for activating and controlling a super-adhesive state are addressed. Even if such a state has never been observed in nanovectors, our calculations, as well as observations in spiders and geckos, suggest its existence and feasible control. Control of the competition between the drag and the adhesive force is exploited to improve the targeting ability and a hierarchical model is applied to describe a real vasculature. The high flexibility of the nanovector is used to smartly deliver the drug only during adhesion by nanopumping or, as a limiting case, by the new concept of 'adhesion induced nanovector implosion'; a liquid drop analogy is utilized for the calculations. Fast (pumping) and slow (diffusion) drug deliveries can thus be separately controlled by controlling the size and shape of the nanovector. Multiple stage nanovectors are also briefly discussed, mimicking aerospace vector strategies.

  1. Flexible Electronics Research Facility

    Data.gov (United States)

    Federal Laboratory Consortium — The Flexible Electronics Research Facility designs, synthesizes, tests, and fabricates materials and devices compatible with flexible substrates for Army information...

  2. Balance and flexibility.

    Science.gov (United States)

    2003-12-01

    The 'work-life balance' and flexible working are currently key buzz terms in the NHS. Those looking for more information on these topics should visit Flexibility at www.flexibility.co.uk for a host of resources designed to support new ways of working, including information on flexible workers and flexible rostering, the legal balancing act for work-life balance and home working.

  3. Flexible biochips for detection of biomolecules

    NARCIS (Netherlands)

    Peter, M.; Schüler, T.; Furthner, F.; Rensing, P.A.; Heck, G.T. van; Schoo, H.F.M.; Möllier, R.; Fritzsche, W.; Breemen, A.J.J.M. van; Meinders, E.R.

    2009-01-01

    Miniaturization of biosensors is envisaged by the development of biochips consisting of parallel microarray patterns of binding sites on rigid substrates, such as glass or silicon. Thin plastic substrates are promising flexible alternatives because of the possibility for large-area roll-to-roll

  4. 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...

  5. GC-rich DNA elements enable replication origin activity in the methylotrophic yeast Pichia pastoris.

    Science.gov (United States)

    Liachko, Ivan; Youngblood, Rachel A; Tsui, Kyle; Bubb, Kerry L; Queitsch, Christine; Raghuraman, M K; Nislow, Corey; Brewer, Bonita J; Dunham, Maitreya J

    2014-03-01

    The well-studied DNA replication origins of the model budding and fission yeasts are A/T-rich elements. However, unlike their yeast counterparts, both plant and metazoan origins are G/C-rich and are associated with transcription start sites. Here we show that an industrially important methylotrophic budding yeast, Pichia pastoris, simultaneously employs at least two types of replication origins--a G/C-rich type associated with transcription start sites and an A/T-rich type more reminiscent of typical budding and fission yeast origins. We used a suite of massively parallel sequencing tools to map and dissect P. pastoris origins comprehensively, to measure their replication dynamics, and to assay the global positioning of nucleosomes across the genome. Our results suggest that some functional overlap exists between promoter sequences and G/C-rich replication origins in P. pastoris and imply an evolutionary bifurcation of the modes of replication initiation.

  6. GC-rich DNA elements enable replication origin activity in the methylotrophic yeast Pichia pastoris.

    Directory of Open Access Journals (Sweden)

    Ivan Liachko

    2014-03-01

    Full Text Available The well-studied DNA replication origins of the model budding and fission yeasts are A/T-rich elements. However, unlike their yeast counterparts, both plant and metazoan origins are G/C-rich and are associated with transcription start sites. Here we show that an industrially important methylotrophic budding yeast, Pichia pastoris, simultaneously employs at least two types of replication origins--a G/C-rich type associated with transcription start sites and an A/T-rich type more reminiscent of typical budding and fission yeast origins. We used a suite of massively parallel sequencing tools to map and dissect P. pastoris origins comprehensively, to measure their replication dynamics, and to assay the global positioning of nucleosomes across the genome. Our results suggest that some functional overlap exists between promoter sequences and G/C-rich replication origins in P. pastoris and imply an evolutionary bifurcation of the modes of replication initiation.

  7. 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.

  8. Tyr120Asp mutation alters domain flexibility and dynamics of MeCP2 DNA binding domain leading to impaired DNA interaction: Atomistic characterization of a Rett syndrome causing mutation.

    Science.gov (United States)

    D'Annessa, Ilda; Gandaglia, Anna; Brivio, Elena; Stefanelli, Gilda; Frasca, Angelisa; Landsberger, Nicoletta; Di Marino, Daniele

    2018-05-01

    Mutations in the X-linked MECP2 gene represent the main origin of Rett syndrome, causing a profound intellectual disability in females. MeCP2 is an epigenetic transcriptional regulator containing two main functional domains: a methyl-CpG binding domain (MBD) and a transcription repression domain (TRD). Over 600 pathogenic mutations were reported to affect the whole protein; almost half of missense mutations affect the MBD. Understanding the impact of these mutations on the MBD structure and interaction with DNA will foster the comprehension of their pathogenicity and possibly genotype/phenotype correlation studies. Herein, we use molecular dynamics simulations to obtain a detailed view of the dynamics of WT and mutated MBD in the presence and absence of DNA. The pathogenic mutation Y120D is used as paradigm for our studies. Further, since the Y120 residue was previously found to be a phosphorylation site, we characterize the dynamic profile of the MBD also in the presence of Y120 phosphorylation (pY120). We found that addition of a phosphate group to Y120 or mutation in aspartic acid affect domain mobility that samples an alternative conformational space with respect to the WT, leading to impaired ability to interact with DNA. Experimental assays showing a significant reduction in the binding affinity between the mutated MBD and the DNA confirmed our predictions. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. 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.

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

    Science.gov (United States)

    Kabir, Ayesha; Suresh Kumar, Gopinatha

    2013-01-01

    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. 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. From a thermodynamic analysis, the AT base specificity of polyamines to DNAs has been elucidated for the first time and supplemented by structural studies.

  11. Flexible magnetoimpedance sensor

    KAUST Repository

    Li, Bodong; Kavaldzhiev, Mincho; Kosel, Jü rgen

    2015-01-01

    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

  12. Flexible Carpooling: Exploratory Study

    OpenAIRE

    Dorinson, Diana; Gay, Deanna; Minett, Paul; Shaheen, Susan

    2009-01-01

    Energy consumption could be reduced if more people shared rides rather than driving alone yet carpooling represents a small proportion of all potential carpoolers. Prior research has found that many who might carpool were concerned about reduced flexibility with carpooling. If flexibility is one of the barriers how could carpooling be organized to be more flexible? In Northern Virginia a flexible system has evolved where there are 3,500 single-use carpools per day. In another example there ...

  13. Combination of Ambiguous and Unambiguous Data in the Restraint-driven Docking of Flexible Peptides with HADDOCK: The Binding of the Spider Toxin PcTx1 to the Acid Sensing Ion Channel (ASIC) 1a.

    Science.gov (United States)

    Deplazes, Evelyne; Davies, Josephine; Bonvin, Alexandre M J J; King, Glenn F; Mark, Alan E

    2016-01-25

    Peptides that bind to ion channels have attracted much interest as potential lead molecules for the development of new drugs and insecticides. However, the structure determination of large peptide-channel complexes using experimental methods is challenging. Thus structural models are often derived from combining experimental information with restraint-driven docking approaches. Using the complex formed by the venom peptide PcTx1 and the acid sensing ion channel (ASIC) 1a as a case study, we have examined the effect of different combinations of restraints and input structures on the statistical likelihood of (a) correctly predicting the structure of the binding interface and (b) the ability to predict which residues are involved in specific pairwise peptide-channel interactions. For this, we have analyzed over 200,000 water-refined docked structures obtained with various amounts and types of restraints of the peptide-channel complex predicted using the docking program HADDOCK. We found that increasing the number of restraints or even the use of pairwise interaction data resulted in only a modest improvement in the likelihood of finding a structure within a given accuracy. This suggests that shape complementarity and the force field make a large contribution to the accuracy of the predicted structure. The results also showed that there are large variations in the accuracy of the predicted structure depending on the precise combination of residues used as restraints. Finally, we reflect on the limitations of relying on geometric criteria such as root-mean square deviations to assess the accuracy of docking procedures. We propose that in addition to currently used measures, the likelihood of finding a structure within a given level of accuracy should be also used to evaluate docking methods.

  14. Dynamic DNA binding, junction recognition and G4 melting activity underlie the telomeric and genome-wide roles of human CST.

    Science.gov (United States)

    Bhattacharjee, Anukana; Wang, Yongyao; Diao, Jiajie; Price, Carolyn M

    2017-12-01

    Human CST (CTC1-STN1-TEN1) is a ssDNA-binding complex that helps resolve replication problems both at telomeres and genome-wide. CST resembles Replication Protein A (RPA) in that the two complexes harbor comparable arrays of OB-folds and have structurally similar small subunits. However, the overall architecture and functions of CST and RPA are distinct. Currently, the mechanism underlying CST action at diverse replication issues remains unclear. To clarify CST mechanism, we examined the capacity of CST to bind and resolve DNA structures found at sites of CST activity. We show that CST binds preferentially to ss-dsDNA junctions, an activity that can explain the incremental nature of telomeric C-strand synthesis following telomerase action. We also show that CST unfolds G-quadruplex structures, thus providing a mechanism for CST to facilitate replication through telomeres and other GC-rich regions. Finally, smFRET analysis indicates that CST binding to ssDNA is dynamic with CST complexes undergoing concentration-dependent self-displacement. These findings support an RPA-based model where dissociation and re-association of individual OB-folds allow CST to mediate loading and unloading of partner proteins to facilitate various aspects of telomere replication and genome-wide resolution of replication stress. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  15. 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.

  16. Office flexible cystoscopy.

    Science.gov (United States)

    Kavoussi, L R; Clayman, R V

    1988-11-01

    Since the development of the first purpose-built flexible cystoscope in 1984, flexible cystoscopy has become an accepted diagnostic and therapeutic modality. Indeed, it is estimated that more than 10 per cent of practicing urologists are already familiar with this technology. The flexible cystoscope has markedly extended the urologist's ability to examine the bladder, and it has become a valuable adjunct to the rigid cystoscope. Although the operation of this instrument is vastly different from that of its rigid counterpart, with practice, the technique can be learned. After experience is obtained with diagnostic flexible cystoscopy, the urologist will likely prefer this new instrument for bladder inspection, as it provides for a more thorough yet less morbid and less expensive examination. In the future, the development of improved and smaller instrumentation will further extend the therapeutic indications for flexible cystoscopy. Indeed, advances in laser technology are already providing the urologist with 300- to 600-micron (0.9 to 1.8F) flexible probes capable of incision (KTP laser), fulguration (Nd:YAG laser), and stone disintegration (tunable dye laser). Lastly, the skills obtained in using the flexible cystoscope are all readily applicable to the development of dexterity with the already available flexible nephroscope and the more recently developed flexible ureteroscope.

  17. Organizational flexibility estimation

    OpenAIRE

    Komarynets, Sofia

    2013-01-01

    By the help of parametric estimation the evaluation scale of organizational flexibility and its parameters was formed. Definite degrees of organizational flexibility and its parameters for the Lviv region enterprises were determined. Grouping of the enterprises under the existing scale was carried out. Special recommendations to correct the enterprises behaviour were given.

  18. 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.

  19. Flexible magnetoimpidence sensor

    KAUST Repository

    Kavaldzhiev, Mincho

    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.

  20. Flexibility within Fidelity

    Science.gov (United States)

    Kendall, Philip C.; Gosch, Elizabeth; Furr, Jami M.; Sood, Erica

    2008-01-01

    The authors address concerns regarding manual-based treatments, highlighting the role of flexibility and creativity. A cognitive-behavioral therapy for youth anxiety called the Coping Cat program demonstrates the flexible application of manuals and emphasizes the importance of a child-centered, personalized approach that involves the child in the…

  1. Flexible position probe assembly

    International Nuclear Information System (INIS)

    Schmitz, J.J.

    1977-01-01

    The combination of a plurality of tubular transducer sections and a flexible supporting member extending through the tubular transducer sections forms a flexible elongated probe of a design suitable for monitoring the level of an element, such as a nuclear magnetically permeable control rod or liquid. 3 claims, 23 figures

  2. 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.

  3. Global Sourcing Flexibility

    DEFF Research Database (Denmark)

    Ørberg Jensen, Peter D.; Petersen, Bent

    2013-01-01

    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...... 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...... and operations against the backdrop of the theory-based definition of the construct. We discuss in particular the importance of global sourcing flexibility for operational performance stability, and the trade-off between specialization benefits, emerging from location and service provider specialization, versus...

  4. 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

    Science.gov (United States)

    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 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

  5. Flexible Word Classes

    DEFF Research Database (Denmark)

    • 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...... that cannot be classified in terms of the traditional lexical categories Verb, Noun, Adjective or Adverb. Flexible words can - without special morphosyntactic marking - serve in functions for which other languages must employ members of two or more of the four traditional, 'specialised' word classes. Thus......, flexible words are underspecified for communicative functions like 'predicating' (verbal function), 'referring' (nominal function) or 'modifying' (a function typically associated with adjectives and e.g. manner adverbs). Even though linguists have been aware of flexible world classes for more than...

  6. Reversibly Bistable Flexible Electronics

    KAUST Repository

    Alfaraj, Nasir

    2015-01-01

    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

  7. Flexibility in insulin prescription

    Directory of Open Access Journals (Sweden)

    Sanjay Kalra

    2016-01-01

    Full Text Available This communication explores the concept of flexibility, a propos insulin preparations and insulin regimes used in the management of type 2 diabetes. The flexibility of an insulin regime or preparation is defined as their ability to be injected at variable times, with variable injection-meal time gaps, in a dose frequency and quantum determined by shared decision making, with a minimal requirement of glucose monitoring and health professional consultation, with no compromise on safety, efficiency and tolerability. The relative flexibility of various basal, prandial and dual action insulins, as well as intensive regimes, is compared. The biopsychosocial model of health is used to assess the utility of different insulins while encouraging a philosophy of flexible insulin usage.

  8. 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.......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....

  9. IGF binding proteins.

    Science.gov (United States)

    Bach, Leon A

    2017-12-18

    Insulin-like growth factor binding proteins (IGFBPs) 1-6 bind IGFs but not insulin with high affinity. They were initially identified as serum carriers and passive inhibitors of IGF actions. However, subsequent studies showed that, although IGFBPs inhibit IGF actions in many circumstances, they may also potentiate these actions. IGFBPs are widely expressed in most tissues, and they are flexible endocrine and autocrine/paracrine regulators of IGF activity, which is essential for this important physiological system. More recently, individual IGFBPs have been shown to have IGF-independent actions. Mechanisms underlying these actions include (i) interaction with non-IGF proteins in compartments including the extracellular space and matrix, the cell surface and intracellularly; (ii) interaction with and modulation of other growth factor pathways including EGF, TGF- and VEGF; and (iii) direct or indirect transcriptional effects following nuclear entry of IGFBPs. Through these IGF-dependent and IGF-independent actions, IGFBPs modulate essential cellular processes including proliferation, survival, migration, senescence, autophagy and angiogenesis. They have been implicated in a range of disorders including malignant, metabolic, neurological and immune diseases. A more complete understanding of their cellular roles may lead to the development of novel IGFBP-based therapeutic opportunities.

  10. Flexible transparent electrode

    Science.gov (United States)

    Demiryont, Hulya; Shannon, Kenneth C., III; Moorehead, David; Bratcher, Matthew

    2011-06-01

    This paper presents the properties of the EclipseTECTM transparent conductor. EclipseTECTM is a room temperature deposited nanostructured thin film coating system comprised of metal-oxide semiconductor elements. The system possesses metal-like conductivity and glass-like transparency in the visible region. These highly conductive TEC films exhibit high shielding efficiency (35dB at 1 to 100GHz). EclipseTECTM can be deposited on rigid or flexible substrates. For example, EclipseTECTM deposited on polyethylene terephthalate (PET) is extremely flexible that can be rolled around a 9mm diameter cylinder with little or no reduction in electrical conductivity and that can assume pre-extension states after an applied stress is relieved. The TEC is colorless and has been tailored to have high visible transmittance which matches the eye sensitivity curve and allows the viewing of true background colors through the coating. EclipseTECTM is flexible, durable and can be tailored at the interface for applications such as electron- or hole-injecting OLED electrodes as well as electrodes in flexible displays. Tunable work function and optical design flexibility also make EclipseTECTM well-suited as a candidate for grid electrode replacement in next-generation photovoltaic cells.

  11. Flexible magnetoimpedance sensor

    International Nuclear Information System (INIS)

    Li, Bodong; Kavaldzhiev, Mincho N.; Kosel, Jürgen

    2015-01-01

    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. - 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

  12. Education for Flexible Personality

    Directory of Open Access Journals (Sweden)

    Bogomir Novak

    1998-12-01

    Full Text Available Flexible personality transforms both cultural environment and itself. Post-modern personality is both contemplative and active. On one hand, it is subject to inner imagination of a creative act, and on the other hand, to creation of a tangible product What is more, flexible personality is also autonomous, mature, healthy and well balanced, as well as stable and responsive to the demand for change. Due to ever quicker changes, flexible personality is a must. And it is a task. The impact of professional work of adults on the education of children, however, is being conditioned by the exrigid family and rigid enterprises or institutions in which adults are employed. Nevertheless, flexible educational style is not repressive, as it used to be, nor permissive and totally concentrated on the child. It is a choice between the two qualities. The educators' style is dependent on their attitude towards life (play and self-education and not only towards work. Nowadays, flexibility is a way towards quality management of social and personal changes.

  13. Flexible Foam Model.

    Energy Technology Data Exchange (ETDEWEB)

    Neilsen, Michael K.; Lu, Wei-Yang; Werner, Brian T.; Scherzinger, William M.; Lo, Chi S.

    2018-03-01

    Experiments were performed to characterize the mechanical response of a 15 pcf flexible polyurethane foam to large deformation at different strain rates and temperatures. Results from these experiments indicated that at room temperature, flexible polyurethane foams exhibit significant nonlinear elastic deformation and nearly return to their original undeformed shape when unloaded. However, when these foams are cooled to temperatures below their glass transition temperature of approximately -35 o C, they behave like rigid polyurethane foams and exhibit significant permanent deformation when compressed. Thus, a new model which captures this dramatic change in behavior with temperature was developed and implemented into SIERRA with the name Flex_Foam to describe the mechanical response of both flexible and rigid foams to large deformation at a variety of temperatures and strain rates. This report includes a description of recent experiments. Next, development of the Flex Foam model for flexible polyurethane and other flexible foams is described. Selection of material parameters are discussed and finite element simulations with the new Flex Foam model are compared with experimental results to show behavior that can be captured with this new model.

  14. Transforming growth factor beta stimulation of biglycan gene expression is potentially mediated by sp1 binding factors

    DEFF Research Database (Denmark)

    Heegaard, Anne-Marie; Xie, Zhongjian; Young, Marian Frances

    2004-01-01

    . In this study, we have investigated the mechanism by which TGF-beta(1), TGF-beta(2) and TGF-beta(3) stimulate biglycan mRNA expression in the osteoblastic cell line MG-63. The cells were transfected with a series of deletional human biglycan promoter constructs and a region in the biglycan 5' DNA was found...... to respond to TGF-beta(1) with increased transcriptional activity in a dose-dependent manner. Also TGF-beta(2) and TGF-beta(3), two structurally highly related TGF-beta isoforms stimulated biglycan transcription. A TGF-beta responsive region was identified within the first 218 bp of the human biglycan...... was abrogated by mithramycin, an inhibitor of Sp1 binding to GC-rich DNA sequences. A mutation in the Sp1 site at -216 to -208 within the -218 biglycan promoter construct substantially diminished the transcriptional up-regulation by TGF-beta(1). Taken together this data shows for the first time that TGF-beta(1...

  15. Natural flexible dermal armor.

    Science.gov (United States)

    Yang, Wen; Chen, Irene H; Gludovatz, Bernd; Zimmermann, Elizabeth A; Ritchie, Robert O; Meyers, Marc A

    2013-01-04

    Fish, reptiles, and mammals can possess flexible dermal armor for protection. Here we seek to find the means by which Nature derives its protection by examining the scales from several fish (Atractosteus spatula, Arapaima gigas, Polypterus senegalus, Morone saxatilis, Cyprinius carpio), and osteoderms from armadillos, alligators, and leatherback turtles. Dermal armor has clearly been developed by convergent evolution in these different species. In general, it has a hierarchical structure with collagen fibers joining more rigid units (scales or osteoderms), thereby increasing flexibility without significantly sacrificing strength, in contrast to rigid monolithic mineral composites. These dermal structures are also multifunctional, with hydrodynamic drag (in fish), coloration for camouflage or intraspecies recognition, temperature and fluid regulation being other important functions. The understanding of such flexible dermal armor is important as it may provide a basis for new synthetic, yet bioinspired, armor materials. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. 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.

  17. Software industrial flexible

    OpenAIRE

    Díaz Araya, Daniel; Muñoz, Leandro; Sirerol, Daniel; Oviedo, Sandra; Ibáñez, Francisco S.

    2012-01-01

    En este trabajo se pretende investigar y proponer técnicas, métodos y tecnologías que permitan el desarrollo de software flexible en ambientes industriales. El objetivo es generar métodos y técnicas para facilitar el desarrollo de software flexible en ambientes industriales. Las áreas de investigación son los sistemas de scheduling de producción, la generación de software para plataformas de hardware abiertas y la innovación.

  18. Production Flexibility and Hedging

    Directory of Open Access Journals (Sweden)

    Georges Dionne

    2015-12-01

    Full Text Available We extend the analysis on hedging with price and output uncertainty by endogenizing the output decision. Specifically, we consider the joint determination of output and hedging in the case of flexibility in production. We show that the risk-averse firm always maintains a short position in the futures market when the futures price is actuarially fair. Moreover, in the context of an example, we show that the presence of production flexibility reduces the incentive to hedge for all risk averse agents.

  19. 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...

  20. An Evaluation of Explicit Receptor Flexibility in Molecular Docking Using Molecular Dynamics and Torsion Angle Molecular Dynamics.

    Science.gov (United States)

    Armen, Roger S; Chen, Jianhan; Brooks, Charles L

    2009-10-13

    Incorporating receptor flexibility into molecular docking should improve results for flexible proteins. However, the incorporation of explicit all-atom flexibility with molecular dynamics for the entire protein chain may also introduce significant error and "noise" that could decrease docking accuracy and deteriorate the ability of a scoring function to rank native-like poses. We address this apparent paradox by comparing the success of several flexible receptor models in cross-docking and multiple receptor ensemble docking for p38α mitogen-activated protein (MAP) kinase. Explicit all-atom receptor flexibility has been incorporated into a CHARMM-based molecular docking method (CDOCKER) using both molecular dynamics (MD) and torsion angle molecular dynamics (TAMD) for the refinement of predicted protein-ligand binding geometries. These flexible receptor models have been evaluated, and the accuracy and efficiency of TAMD sampling is directly compared to MD sampling. Several flexible receptor models are compared, encompassing flexible side chains, flexible loops, multiple flexible backbone segments, and treatment of the entire chain as flexible. We find that although including side chain and some backbone flexibility is required for improved docking accuracy as expected, docking accuracy also diminishes as additional and unnecessary receptor flexibility is included into the conformational search space. Ensemble docking results demonstrate that including protein flexibility leads to to improved agreement with binding data for 227 active compounds. This comparison also demonstrates that a flexible receptor model enriches high affinity compound identification without significantly increasing the number of false positives from low affinity compounds.

  1. Flexibility as a service

    NARCIS (Netherlands)

    Aalst, van der W.M.P.; Adams, M.; Hofstede, ter A.H.M.; Pesic, M.; Schonenberg, H.; Chen, L.; Liu, C.; Liu, Q.; Deng, K.

    2009-01-01

    The lack of flexibility is often seen as an inhibitor for the successful application of workflow technology. Many researchers have proposed different ways of addressing this problem and some of these ideas have been implemented in commercial systems. However, a "one size fits all" approach is likely

  2. Valuing Flexibility. Phase 2

    Science.gov (United States)

    2012-10-29

    Quarterly (2): 38-49. Cormier, P., Olewnik, A., and Lewis, K. 2008. An Approach to Quantifying Design Flexibility for Mass Customization in Early...C. Clarkson, P., and Zanker, W. 2004. Change and customisation in complex engineering domains, Res Eng Des 15(1), 1–21. Ekstrom, M. and Bjornsson, H

  3. Flexible Query Answering Systems

    DEFF Research Database (Denmark)

    This book constitutes the refereed proceedings of the 12th International Conference on Flexible Query Answering Systems, FQAS 2017, held in London, UK, in June 2017. The 21 full papers presented in this book together with 4 short papers were carefully reviewed and selected from 43 submissions...

  4. Flexible metal bellows

    CERN Multimedia

    CERN PhotoLab

    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.

  5. 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....

  6. A flexible WLAN receiver

    NARCIS (Netherlands)

    Schiphorst, Roelof; Hoeksema, F.W.; Slump, Cornelis H.

    2003-01-01

    Flexible radio receivers are also called Software Defined Radios (SDRs) [1], [2]. The focus of our SDR project [3] is on designing the front end, from antenna to demodulation in bits, of a °exible, multi-standard WLAN receiver. We try to combine an instance of a (G)FSK receiver (Bluetooth) with an

  7. Global mapping of DNA conformational flexibility on Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Giulia Menconi

    2015-04-01

    Full Text Available In this study we provide the first comprehensive map of DNA conformational flexibility in Saccharomyces cerevisiae complete genome. Flexibility plays a key role in DNA supercoiling and DNA/protein binding, regulating DNA transcription, replication or repair. Specific interest in flexibility analysis concerns its relationship with human genome instability. Enrichment in flexible sequences has been detected in unstable regions of human genome defined fragile sites, where genes map and carry frequent deletions and rearrangements in cancer. Flexible sequences have been suggested to be the determinants of fragile gene proneness to breakage; however, their actual role and properties remain elusive. Our in silico analysis carried out genome-wide via the StabFlex algorithm, shows the conserved presence of highly flexible regions in budding yeast genome as well as in genomes of other Saccharomyces sensu stricto species. Flexibile peaks in S. cerevisiae identify 175 ORFs mapping on their 3'UTR, a region affecting mRNA translation, localization and stability. (TAn repeats of different extension shape the central structure of peaks and co-localize with polyadenylation efficiency element (EE signals. ORFs with flexible peaks share common features. Transcripts are characterized by decreased half-life: this is considered peculiar of genes involved in regulatory systems with high turnover; consistently, their function affects biological processes such as cell cycle regulation or stress response. Our findings support the functional importance of flexibility peaks, suggesting that the flexible sequence may be derived by an expansion of canonical TAYRTA polyadenylation efficiency element. The flexible (TAn repeat amplification could be the outcome of an evolutionary neofunctionalization leading to a differential 3'-end processing and expression regulation in genes with peculiar function. Our study provides a new support to the functional role of flexibility in

  8. Global mapping of DNA conformational flexibility on Saccharomyces cerevisiae.

    Science.gov (United States)

    Menconi, Giulia; Bedini, Andrea; Barale, Roberto; Sbrana, Isabella

    2015-04-01

    In this study we provide the first comprehensive map of DNA conformational flexibility in Saccharomyces cerevisiae complete genome. Flexibility plays a key role in DNA supercoiling and DNA/protein binding, regulating DNA transcription, replication or repair. Specific interest in flexibility analysis concerns its relationship with human genome instability. Enrichment in flexible sequences has been detected in unstable regions of human genome defined fragile sites, where genes map and carry frequent deletions and rearrangements in cancer. Flexible sequences have been suggested to be the determinants of fragile gene proneness to breakage; however, their actual role and properties remain elusive. Our in silico analysis carried out genome-wide via the StabFlex algorithm, shows the conserved presence of highly flexible regions in budding yeast genome as well as in genomes of other Saccharomyces sensu stricto species. Flexibile peaks in S. cerevisiae identify 175 ORFs mapping on their 3'UTR, a region affecting mRNA translation, localization and stability. (TA)n repeats of different extension shape the central structure of peaks and co-localize with polyadenylation efficiency element (EE) signals. ORFs with flexible peaks share common features. Transcripts are characterized by decreased half-life: this is considered peculiar of genes involved in regulatory systems with high turnover; consistently, their function affects biological processes such as cell cycle regulation or stress response. Our findings support the functional importance of flexibility peaks, suggesting that the flexible sequence may be derived by an expansion of canonical TAYRTA polyadenylation efficiency element. The flexible (TA)n repeat amplification could be the outcome of an evolutionary neofunctionalization leading to a differential 3'-end processing and expression regulation in genes with peculiar function. Our study provides a new support to the functional role of flexibility in genomes and a

  9. Energy Flexibility in Retail Buildings

    DEFF Research Database (Denmark)

    Ma, Zheng; Billanes, Joy Dalmacio; Kjærgaard, Mikkel Baun

    2017-01-01

    Retail buildings has an important role for demand side energy flexibility because of their high energy consumption, variety of energy flexibility resources, and centralized control via building control systems. Energy flexibility requires agreements and collaborations among different actors......), with the discussion of the stakeholders’ roles and their interrelation in delivering energy flexibility with the influential factors to the actual implementation of energy flexible operation of their buildings. Based on a literature analysis, the results cover stakeholders’ types and roles, perceptions (drivers......, barriers, and benefits), energy management activities and technology adoptions, and the stakeholders’ interaction for the energy flexibility in retail buildings....

  10. 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)

  11. Flexible cryogenic conduit

    International Nuclear Information System (INIS)

    Brindza, P.D.; Wines, R.R.; Takacs, J.J.

    1999-01-01

    A flexible and relatively low cost cryogenic conduit is described. The flexible cryogenic conduit of the present invention comprises a first inner corrugated tube with single braided serving, a second outer corrugated tube with single braided serving concentric with the inner corrugated tube, and arranged outwardly about the periphery of the inner corrugated tube and between the inner and outer corrugated tubes: a superinsulation layer; a one half lap layer of polyester ribbon; a one half lap layer of copper ribbon; a spirally wound refrigeration tube; a second one half lap layer of copper ribbon; a second one half lap layer of polyester ribbon; a second superinsulation layer; a third one half lap layer of polyester ribbon; and a spirally wound stretchable and compressible filament

  12. 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)

  13. 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....

  14. Flexible training under threat.

    Science.gov (United States)

    Houghton, Anita; Eaton, Jennifer

    2002-10-01

    As the number of women in medicine and the general demand for a better work-life balance rises, flexible training is an increasingly important mechanism for maintaining the medical workforce. The new pay deal, together with entrenched cultural attitudes, are potential threats. Ways forward include more substantive part-time posts, more part-time opportunities at consultant level, and using positive experiences as a way of tackling attitudes in the less accepting specialties.

  15. Flexible weapons architecture design

    OpenAIRE

    Pyant, William C.

    2015-01-01

    Present day air-delivered weapons are of a closed architecture, with little to no ability to tailor the weapon for the individual engagement. The closed architectures require weaponeers to make the target fit the weapon instead of fitting the individual weapons to a target. The concept of a flexible weapons aims to modularize weapons design using an open architecture shell into which different modules are inserted to achieve the desired target fractional damage while reducing cost and civilia...

  16. 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.

  17. 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....

  18. PTFE films with improved flexibility

    Science.gov (United States)

    Muraca, R. F.; Koch, A. A.

    1972-01-01

    Development and application of flexible polytetrafluroethylene films for expulsion bladders in spacecraft propellant tanks are described. Flexibility of material is obtained by reducing crystallinity through annealing and quenching in water. Physical and mechanical properties of material are presented.

  19. Structure-based Understanding of Binding Affinity and Mode of Estrogen Receptor α Agonists and Antagonists.

    Science.gov (United States)

    The flexible hydrophobic ligand binding pocket (LBP) of estrogen receptor α (ERα) allows the binding of a wide variety of endocrine disruptors. Upon ligand binding, the LBP reshapes around the contours of the ligand and stabilizes the complex by complementary hydrophobic interact...

  20. Flexible automated manufacturing for SMEs

    DEFF Research Database (Denmark)

    Grube Hansen, David; Bilberg, Arne; Madsen, Erik Skov

    2017-01-01

    SMEs are in general highly flexible and agile in order to accommodate the customer demands in the paradigm of High Mix-Low Volume manufacturing. The flexibility and agility have mainly been enabled by manual labor, but as we are entering the technology and data driven fourth industrial revolution......, where augmented operators and machines work in cooperation in a highly flexible and productive manufacturing system both an opportunity and a need has raised for developing highly flexible and efficient automation....

  1. Investigation of arc repressor DNA-binding specificity by comparative molecular dynamics simulations.

    Science.gov (United States)

    Song, Wei; Guo, Jun-Tao

    2015-01-01

    Transcription factors regulate gene expression through binding to specific DNA sequences. How transcription factors achieve high binding specificity is still not well understood. In this paper, we investigated the role of protein flexibility in protein-DNA-binding specificity by comparative molecular dynamics (MD) simulations. Protein flexibility has been considered as a key factor in molecular recognition, which is intrinsically a dynamic process involving fine structural fitting between binding components. In this study, we performed comparative MD simulations on wild-type and F10V mutant P22 Arc repressor in both free and complex conformations. The F10V mutant has lower DNA-binding specificity though both the bound and unbound main-chain structures between the wild-type and F10V mutant Arc are highly similar. We found that the DNA-binding motif of wild-type Arc is structurally more flexible than the F10V mutant in the unbound state, especially for the six DNA base-contacting residues in each dimer. We demonstrated that the flexible side chains of wild-type Arc lead to a higher DNA-binding specificity through forming more hydrogen bonds with DNA bases upon binding. Our simulations also showed a possible conformational selection mechanism for Arc-DNA binding. These results indicate the important roles of protein flexibility and dynamic properties in protein-DNA-binding specificity.

  2. 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

  3. 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...

  4. 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...

  5. Implicit ligand theory for relative binding free energies

    Science.gov (United States)

    Nguyen, Trung Hai; Minh, David D. L.

    2018-03-01

    Implicit ligand theory enables noncovalent binding free energies to be calculated based on an exponential average of the binding potential of mean force (BPMF)—the binding free energy between a flexible ligand and rigid receptor—over a precomputed ensemble of receptor configurations. In the original formalism, receptor configurations were drawn from or reweighted to the apo ensemble. Here we show that BPMFs averaged over a holo ensemble yield binding free energies relative to the reference ligand that specifies the ensemble. When using receptor snapshots from an alchemical simulation with a single ligand, the new statistical estimator outperforms the original.

  6. Identification of Plagl1/Zac1 binding sites and target genes establishes its role in the regulation of extracellular matrix genes and the imprinted gene network.

    Science.gov (United States)

    Varrault, Annie; Dantec, Christelle; Le Digarcher, Anne; Chotard, Laëtitia; Bilanges, Benoit; Parrinello, Hugues; Dubois, Emeric; Rialle, Stéphanie; Severac, Dany; Bouschet, Tristan; Journot, Laurent

    2017-10-13

    PLAGL1/ZAC1 undergoes parental genomic imprinting, is paternally expressed, and is a member of the imprinted gene network (IGN). It encodes a zinc finger transcription factor with anti-proliferative activity and is a candidate tumor suppressor gene on 6q24 whose expression is frequently lost in various neoplasms. Conversely, gain of PLAGL1 function is responsible for transient neonatal diabetes mellitus, a rare genetic disease that results from defective pancreas development. In the present work, we showed that Plagl1 up-regulation was not associated with DNA damage-induced cell cycle arrest. It was rather associated with physiological cell cycle exit that occurred with contact inhibition, growth factor withdrawal, or cell differentiation. To gain insights into Plagl1 mechanism of action, we identified Plagl1 target genes by combining chromatin immunoprecipitation and genome-wide transcriptomics in transfected cell lines. Plagl1-elicited gene regulation correlated with multiple binding to the proximal promoter region through a GC-rich motif. Plagl1 target genes included numerous genes involved in signaling, cell adhesion, and extracellular matrix composition, including collagens. Plagl1 targets also included 22% of the 409 genes that make up the IGN. Altogether, this work identified Plagl1 as a transcription factor that coordinated the regulation of a subset of IGN genes and controlled extracellular matrix composition. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  7. 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.

  8. Origin of an alternative genetic code in the extremely small and GC-rich genome of a bacterial symbiont.

    Directory of Open Access Journals (Sweden)

    John P McCutcheon

    2009-07-01

    Full Text Available The genetic code relates nucleotide sequence to amino acid sequence and is shared across all organisms, with the rare exceptions of lineages in which one or a few codons have acquired novel assignments. Recoding of UGA from stop to tryptophan has evolved independently in certain reduced bacterial genomes, including those of the mycoplasmas and some mitochondria. Small genomes typically exhibit low guanine plus cytosine (GC content, and this bias in base composition has been proposed to drive UGA Stop to Tryptophan (Stop-->Trp recoding. Using a combination of genome sequencing and high-throughput proteomics, we show that an alpha-Proteobacterial symbiont of cicadas has the unprecedented combination of an extremely small genome (144 kb, a GC-biased base composition (58.4%, and a coding reassignment of UGA Stop-->Trp. Although it is not clear why this tiny genome lacks the low GC content typical of other small bacterial genomes, these observations support a role of genome reduction rather than base composition as a driver of codon reassignment.

  9. On flexible and rigid nouns

    DEFF Research Database (Denmark)

    Rijkhoff, Jan

    2010-01-01

    classes. Finally this article wants to claim that the distinction between rigid and flexible noun categories (a) adds a new dimension to current classifications of parts of speech systems, (b) correlates with certain grammatical phenomena (e.g. so-called number discord), and (c) helps to explain the parts......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...... by the flexible item in the external world. I will then argue that flexible word classes constitute a proper category (i.e. they are not the result of a merger of some rigid word classes) in that members of flexible word categories display the same properties regarding category membership as members of rigid word...

  10. On flexible and rigid nouns

    DEFF Research Database (Denmark)

    Rijkhoff, Jan

    2008-01-01

    Studies in Language 32-3 (2008), 727-752. Special issue: Parts of Speech: Descriptive tools, theoretical constructs Jan Rijkhoff - On flexible and rigid nouns This article argues that in addition to the 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 of flexible word classes are characterized by their vague semantics, which in the case of nouns means that values for the semantic features Shape...... and Homogeneity are either left undetermined or they are specified in such a way that they do not quite match the properties of the kind of entity denoted by the flexible item in the external world. I will then argue that flexible word classes constitute a proper category (i.e. they are not the result of a merger...

  11. Flexible Language Interoperability

    DEFF Research Database (Denmark)

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

    2007-01-01

    Virtual machines raise the abstraction level of the execution environment at the cost of restricting the set of supported languages. Moreover, the ability of a language implementation to integrate with other languages hosted on the same virtual machine typically constrains the features...... 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...... of a given class. This approach can be deployed both on a statically typed virtual machine, such as the JVM, and on a dynamic virtual machine, such as a Smalltalk virtual machine. We have implemented our approach to language interoperability on top of a prototype virtual machine for embedded systems based...

  12. Flexible cultural repertoires

    DEFF Research Database (Denmark)

    Lindegaard, Marie Rosenkrantz; Zimmermann, Francisca

    2017-01-01

    Despite extensive studies of street culture and the risks of offending and victimization in urban marginalized areas, little is known about the role of cultural repertoires for variation in victimization risks among young men not involved in crime. Based on two ethnographic studies, conducted...... independently of the authors in neighbouring township areas of Cape Town, we offer insights into patterns of victimization among young men not involved in crime who live and attend school in the townships. Young men WHO perform decent cultural repertoires are highly exposed to victimization due to their moral...... rejection of crime-involved youth. Young men who perform flexible cultural repertoires, by incorporating and shifting between gang and decent repertoires, experience low victimization due to their adaptation to crime-involved youth. Findings emphasize the importance of detailed investigations of the way...

  13. Flexible helical yarn swimmers.

    Science.gov (United States)

    Zakharov, A P; Leshansky, A M; Pismen, L M

    2016-09-01

    We investigate the motion of a flexible Stokesian flagellar swimmer realised as a yarn made of two intertwined elastomer fibres, one active, that can reversibly change its length in response to a local excitation causing transition to the nematic state or swelling, and the other one, a passive isotropic elastomer with identical mechanical properties. A propagating chemical wave may provide an excitation mechanism ensuring a constant length of the excited region. Generally, the swimmer moves along a helical trajectory, and the propagation and rotation velocity are very sensitive to the ratio of the excited region to the pitch of the yarn, as well as to the size of a carried load. External excitation by a moving actuating beam is less effective, unless the direction of the beam is adjusted to rotation of the swimmer.

  14. Flexible weapons architecture design

    Science.gov (United States)

    Pyant, William C., III

    Present day air-delivered weapons are of a closed architecture, with little to no ability to tailor the weapon for the individual engagement. The closed architectures require weaponeers to make the target fit the weapon instead of fitting the individual weapons to a target. The concept of a flexible weapons aims to modularize weapons design using an open architecture shell into which different modules are inserted to achieve the desired target fractional damage while reducing cost and civilian casualties. This thesis shows that the architecture design factors of damage mechanism, fusing, weapons weight, guidance, and propulsion are significant in enhancing weapon performance objectives, and would benefit from modularization. Additionally, this thesis constructs an algorithm that can be used to design a weapon set for a particular target class based on these modular components.

  15. 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. © 2016 Wiley Periodicals, Inc.

  16. Using the fast fourier transform in binding free energy calculations.

    Science.gov (United States)

    Nguyen, Trung Hai; Zhou, Huan-Xiang; Minh, David D L

    2018-04-30

    According to implicit ligand theory, the standard binding free energy is an exponential average of the binding potential of mean force (BPMF), an exponential average of the interaction energy between the unbound ligand ensemble and a rigid receptor. Here, we use the fast Fourier transform (FFT) to efficiently evaluate BPMFs by calculating interaction energies when rigid ligand configurations from the unbound ensemble are discretely translated across rigid receptor conformations. Results for standard binding free energies between T4 lysozyme and 141 small organic molecules are in good agreement with previous alchemical calculations based on (1) a flexible complex ( R≈0.9 for 24 systems) and (2) flexible ligand with multiple rigid receptor configurations ( R≈0.8 for 141 systems). While the FFT is routinely used for molecular docking, to our knowledge this is the first time that the algorithm has been used for rigorous binding free energy calculations. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  17. Building flexible real-time systems using the Flex language

    Science.gov (United States)

    Kenny, Kevin B.; Lin, Kwei-Jay

    1991-01-01

    The design and implementation of a real-time programming language called Flex, which is a derivative of C++, are presented. It is shown how different types of timing requirements might be expressed and enforced in Flex, how they might be fulfilled in a flexible way using different program models, and how the programming environment can help in making binding and scheduling decisions. The timing constraint primitives in Flex are easy to use yet powerful enough to define both independent and relative timing constraints. Program models like imprecise computation and performance polymorphism can carry out flexible real-time programs. In addition, programmers can use a performance measurement tool that produces statistically correct timing models to predict the expected execution time of a program and to help make binding decisions. A real-time programming environment is also presented.

  18. 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 ...

  19. Special Issue: Flexible Work Arrangements.

    Science.gov (United States)

    Olmstead, Barney, Ed.

    1996-01-01

    Section 1 contains five chapters on flexible work arrangements, self-employment, working from home, part-time professionals, job sharing, and temporary employment. Section 2 includes reviews of four books on working flexibly, concluding with a list of 23 additional readings. (SK)

  20. Measuring and Comparing Energy Flexibilities

    DEFF Research Database (Denmark)

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

    2015-01-01

    induced by time and amount individually, and by their com- bination. To this end, we introduce several flexibility measures that take into account the combined effect of time and energy on flex-offer flexibility and discuss their respective pros and cons through a number of realistic examples....

  1. 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.

  2. Flexible ring seal

    International Nuclear Information System (INIS)

    Abbes, Claude; Gournier, Andre; Rouaud, Christian; Villepoix, Raymond de.

    1976-01-01

    The invention concerns a flexible metal ring seal, able to ensure a perfect seal between two bearings due to the crushing and elastic deformation properties akin to similar properties in elastomers. Various designs of seal of this kind are already known, particularly a seal made of a core formed by a helical wire spring with close-wound turns and with high axial compression ratio, closed on itself and having the shape of an annulus. This wire ring is surrounded by at least one envelope having at rest the shape of a toroidal surface of which the generating circle does not close on itself. In a particular design mode, the seal in question can include, around the internal spring, two envelopes of which one in contact with the spring is composed of a low ductility elastic metal, such as mild steel or stainless steel and the other is, on the contrary, made of a malleable metal, such as copper or nickel. The first envelope evenly distributes the partial crushing of the spring, when the seal is tightened, on the second envelope which closely fits the two surfaces between which the seal operates. The stress-crushing curve characteristic of the seal comprises two separate parts, the first with a relatively sharp slope corresponds to the start of the seal compression phase, enabling at least some of these curves to reach the requisite seal threshold very quickly, then, beyond this, a second part, practically flat, where the stress is appreciably constant for a wide operating bracket [fr

  3. Flexible piezotronic strain sensor.

    Science.gov (United States)

    Zhou, Jun; Gu, Yudong; Fei, Peng; Mai, Wenjie; Gao, Yifan; Yang, Rusen; Bao, Gang; Wang, Zhong Lin

    2008-09-01

    Strain sensors based on individual ZnO piezoelectric fine-wires (PFWs; nanowires, microwires) have been fabricated by a simple, reliable, and cost-effective technique. The electromechanical sensor device consists of a single electrically connected PFW that is placed on the outer surface of a flexible polystyrene (PS) substrate and bonded at its two ends. The entire device is fully packaged by a polydimethylsiloxane (PDMS) thin layer. The PFW has Schottky contacts at its two ends but with distinctly different barrier heights. The I- V characteristic is highly sensitive to strain mainly due to the change in Schottky barrier height (SBH), which scales linear with strain. The change in SBH is suggested owing to the strain induced band structure change and piezoelectric effect. The experimental data can be well-described by the thermionic emission-diffusion model. A gauge factor of as high as 1250 has been demonstrated, which is 25% higher than the best gauge factor demonstrated for carbon nanotubes. The strain sensor developed here has applications in strain and stress measurements in cell biology, biomedical sciences, MEMS devices, structure monitoring, and more.

  4. Orthogonal flexible Rydberg aggregates

    Science.gov (United States)

    Leonhardt, K.; Wüster, S.; Rost, J. M.

    2016-02-01

    We study the link between atomic motion and exciton transport in flexible Rydberg aggregates, assemblies of highly excited light alkali-metal 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 nonadiabatic 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 nonadiabatic 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 et al., Phys. Rev. Lett. 113, 223001 (2014), 10.1103/PhysRevLett.113.223001]. In this article we discuss the underlying complex dynamics in detail, characterize the switch, and derive our isotropic interaction model from a realistic anisotropic one with the addition of a magnetic bias field.

  5. SOCMA study urges flexibility

    International Nuclear Information System (INIS)

    Kirschner, E.

    1993-01-01

    In implementing the 1990 Pollution Prevention Act, regulators and legislators should hold off on cookie-cutter, numerical goal-based requirements to allow for site and process specific programs, says a study sponsored by the Synthetic Organic Chemicals Manufacturers Association (SOCMA; Washington). Companies should have that flexibility to target their resources toward those activities that reduce pollution cost effectively, says SOCMA environmental quality committee chairman Art Gillen, who is also BASF director of environmental regulatory affairs. The study - conducted by Woodward-Clyde Consultants (Denver) - examines four batch and custom chemical manufacturing films. As in the Clean Air Act, the batch processing of SOCMA-member plants should be considered in new regulations, Gillen says. For example, the study found that most wastes are from shutdowns and cleanouts, and there are frequent charges in waste streams and raw materials. Those characteristics do not lend themselves to annual reduction goals. Also, specific goals could have a wide range of costs: measures to reduce stack air emissions run from $18/lb to $1,106/lb. SOCMA says it will present the study to Congress and the Environmental Protection Agency

  6. Integrated engineering increases flexibility

    International Nuclear Information System (INIS)

    Smith, Ray

    1991-01-01

    Integrated Engineering (IE) can be used to describe the best use of increasingly rare good engineering talent in an increasingly competive world. A number of organisations are now moving towards IE without any general agreement on a precise definition. The engineering division of British Nuclear Fuels (BNFL) is one such organisation. This feature covers the reasoning behind the decision, and our experience to date. BNFL engineering division is responsible primarily for the provision of major facilities on BNFL operational sites. This provision includes feasibility, front end and detailed design, procurement, installation and commissioning. Task force working has been used for some of the large projects. But the future workload is expected to comprise many more smaller projects. At the same time, equipment is becoming more complex and the need for mutual understanding and appreciation between disciplines is increasing. To meet this increasing need for flexibility, BNFL has decided to move to the matrix structure of project management and functional departments described in the article. (Author)

  7. Flexibility in fuel manufacturing

    International Nuclear Information System (INIS)

    Reparaz, A.; Stavig, W.E.; McLees, R.B.

    1987-01-01

    From its inception Exxon Nuclear has produced both BWR and PWR fuels. This is reflected in a product line that, to date, includes over 20 fuel designs. These range from 6x6 design at one end of the spectrum to the recently introduced 17x17 design. The benefits offered include close tailoring of the fuel design to match the customer's requirements, and the ability to rapidly introduce product changes, such as the axial blanket design, with a minimal impact on manufacturing. This flexibility places a number of demands on the manufacturing organization. Close interfaces must be established, and maintained, between the marketing, product design, manufacturing, purchasing and quality organizations, and the information flows must be immediate and accurate. Production schedules must be well planned and must be maintained or revised to reflect changing circumstances. Finally, the manufacturing facilities must be designed to allow rapid switchover between product designs with minor tooling changes and/or rerouting of product flows to alternate work stations. Among the tools used to manage the flow of information and to maintain the tight integration necessary between the various manufacturing, engineering and quality organizations is a commercially available, computerized planning and tracking system, AMAPS. A real-time production data collection system has been designed which gathers data from each production work station for use by the shop floor control module of AMAPS. Accuracy of input to the system is improved through extensive use of bar codes to gather information on the product as it moves through and between work stations. This computerized preparation of material tracing has an impact on direct manufacturing records, quality control records, nuclear material records and accounting and inventory records. This is of benefit to both Exxon Nuclear and its customers

  8. Incentivizing Flexibility in System Operations

    Energy Technology Data Exchange (ETDEWEB)

    Milligan, Michael [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Bloom, Aaron P [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Townsend, Aaron [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Ela, Erik [Electric Power Research Institute; Botterud, Audun [Argonne National Laboratory; Levin, Todd [Argonne National Laboratory

    2018-02-15

    Defining flexibility has been a challenge that a number of industry members and researchers have attempted to address in recent years. With increased variability and uncertainty of variable generation (VG), the resources on the system will have to be more flexible to adjust output, so that power output ranges, power ramp rates, and energy duration sustainability are sufficient to meet the needs of balancing supply with demand at various operational timescales. This chapter discusses whether existing market designs provide adequate incentives for resources to offer their flexibility into the market to meet the increased levels of variability and uncertainty introduced by VG in the short-term operational time frame. It presents a definition of flexibility and discusses how increased levels of VG require increased needs for flexibility on power systems. Following this introductory material, the chapter examines how existing market designs ensure that resources have the right incentives to provide increased flexibility, and then discusses a number of emerging market design elements that impact flexibility incentives.

  9. 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...... and aiming at energy balancing during aggregation. In more detail, this paper considers the complete life cycle of flex-objects: aggregation, disaggregation, associated requirements, efficient incremental computation, and balance aggregation techniques. Extensive experiments based on real-world data from...

  10. Flexible Thermoelectric Generators on Silicon Fabric

    KAUST Repository

    Sevilla, Galo T.

    2012-01-01

    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

  11. Flexibility of trunnion piping elbows

    International Nuclear Information System (INIS)

    Lewis, G.D.; Chao, Y.J.

    1987-01-01

    Flexibility factors and stress indices for piping component such as straight pipe, elbows, butt-welding tees, branch connections, and butt-welding reducers are contained in the code, but many of the less common piping components, like the trunnion elbow, do not have flexibility factors or stress indices defined. The purpose of this paper is to identify the in-plane and out-of-plane flexibility factors in accordance with code procedures for welded trunnions attached to the tangent centerlines of long radius elbows. This work utilized the finite element method as applicable to plates and shells for calculating the relative rotations of the trunnion elbow-ends for in-plane and out-of-plane elbow moment loadings. These rotations are used to derive the corresponding in-plane and out-of-plane flexibility factors. (orig./GL)

  12. Distributed flexibility in inertial swimmers

    Science.gov (United States)

    Floryan, Daniel; Rowley, Clarence W.; Smits, Alexander J.

    2017-11-01

    To achieve fast and efficient swimming, the flexibility of the propulsive surfaces is an important feature. To better understand the effects of distributed flexibility (either through inhomogeneous material properties, varying geometry, or both) we consider the coupled solid and fluid mechanics of the problem. Here, we develop a simplified model of a flexible swimmer, using Euler-Bernoulli theory to describe the solid, Theodorsen's theory to describe the fluid, and a Blasius boundary layer to incorporate viscous effects. Our primary aims are to understand how distributed flexibility affects the thrust production and efficiency of a swimmer with imposed motion at its leading edge. In particular, we examine the modal shapes of the swimmer to gain physical insight into the observed trends. Supported under ONR MURI Grant N00014-14-1-0533, Program Manager Robert Brizzolara.

  13. c-MYC G-quadruplex binding by the RNA polymerase I inhibitor BMH-21 and analogues revealed by a combined NMR and biochemical Approach.

    Science.gov (United States)

    Musso, Loana; Mazzini, Stefania; Rossini, Anna; Castagnoli, Lorenzo; Scaglioni, Leonardo; Artali, Roberto; Di Nicola, Massimo; Zunino, Franco; Dallavalle, Sabrina

    2018-03-01

    Pyridoquinazolinecarboxamides have been reported as RNA polymerase I inhibitors and represent a novel class of potential antitumor agents. BMH-21, was reported to intercalate with GC-rich rDNA, resulting in nucleolar stress as a primary mechanism of cytotoxicity. The interaction of BMH-21 and analogues with DNA G-quadruplex structures was studied by NMR and molecular modelling. The cellular response was investigated in a panel of human tumor cell lines and protein expression was examined by Western Blot analysis. We explored the ability of BMH-21 and its analogue 2 to bind to G-quadruplex present in the c-MYC promoter, by NMR and molecular modelling studies. We provide evidence that both compounds are not typical DNA intercalators but are effective binders of the tested G-quadruplex. The interaction with c-MYC G-quadruplex was reflected in down-regulation of c-Myc expression in human tumor cells. The inhibitory effect was almost complete in lymphoma cells SUDHL4 characterized by overexpression of c-Myc protein. This downregulation reflected an early and persistent modulation of cMyc mRNA. Given the relevance of c-MYC in regulation of ribosome biogenesis, it is conceivable that the inhibition of c-MYC contributes to the perturbation of nuclear functions and RNA polymerase I activity. Similar experiments with CX-5461, another RNA polymerase I transcription inhibitor, indicate the same behaviour in G-quadruplex stabilization. Our results support the hypothesis that BMH-21 and analogue compounds share the same mechanism, i.e. G-quadruplex binding as a primary event of a cascade leading to inhibition of RNA polymerase I and apoptosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. 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...

  15. Workplace flexibility across the lifespan

    OpenAIRE

    Bal, Pieter; Jansen, Paul G W

    2016-01-01

    As demographic changes impact the workplace, governments, organizations and workers arelooking for ways to sustain optimal working lives at higher ages. Workplace flexibility has beenintroduced as a potential way workers can have more satisfying working lives until theirretirement ages. This paper presents a critical review of the literature on workplace flexibilityacross the lifespan. It discusses how flexibility has been conceptualized across differentdisciplines, and postulates a definitio...

  16. Flexible packaging for PV modules

    Science.gov (United States)

    Dhere, Neelkanth G.

    2008-08-01

    Economic, flexible packages that provide needed level of protection to organic and some other PV cells over >25-years have not yet been developed. However, flexible packaging is essential in niche large-scale applications. Typical configuration used in flexible photovoltaic (PV) module packaging is transparent frontsheet/encapsulant/PV cells/flexible substrate. Besides flexibility of various components, the solder bonds should also be flexible and resistant to fatigue due to cyclic loading. Flexible front sheets should provide optical transparency, mechanical protection, scratch resistance, dielectric isolation, water resistance, UV stability and adhesion to encapsulant. Examples are Tefzel, Tedlar and Silicone. Dirt can get embedded in soft layers such as silicone and obscure light. Water vapor transmittance rate (WVTR) of polymer films used in the food packaging industry as moisture barriers are ~0.05 g/(m2.day) under ambient conditions. In comparison, light emitting diodes employ packaging components that have WVTR of ~10-6 g/(m2.day). WVTR of polymer sheets can be improved by coating them with dense inorganic/organic multilayers. Ethylene vinyl acetate, an amorphous copolymer used predominantly by the PV industry has very high O2 and H2O diffusivity. Quaternary carbon chains (such as acetate) in a polymer lead to cleavage and loss of adhesional strength at relatively low exposures. Reactivity of PV module components increases in presence of O2 and H2O. Adhesional strength degrades due to the breakdown of structure of polymer by reactive, free radicals formed by high-energy radiation. Free radical formation in polymers is reduced when the aromatic rings are attached at regular intervals. This paper will review flexible packaging for PV modules.

  17. Flexible forms of working hours

    OpenAIRE

    Knapp, Viktor

    2017-01-01

    66 Abstract - Flexible forms of working hours This diploma thesis deals with the flexible forms of working hours and its goal is to describe this issue in intelligible and comprehensive way. It is being very interesting and current theme which is to a great extent not subject to direct legal regulations and provides its contracting parties with a big amount of freedom of contract. This fact assists in bigger flexibilization of labour market and represents a significant instrument in the fight...

  18. Developmental constraints on behavioural flexibility.

    Science.gov (United States)

    Holekamp, Kay E; Swanson, Eli M; Van Meter, Page E

    2013-05-19

    We suggest that variation in mammalian behavioural flexibility not accounted for by current socioecological models may be explained in part by developmental constraints. From our own work, we provide examples of constraints affecting variation in behavioural flexibility, not only among individuals, but also among species and higher taxonomic units. We first implicate organizational maternal effects of androgens in shaping individual differences in aggressive behaviour emitted by female spotted hyaenas throughout the lifespan. We then compare carnivores and primates with respect to their locomotor and craniofacial adaptations. We inquire whether antagonistic selection pressures on the skull might impose differential functional constraints on evolvability of skulls and brains in these two orders, thus ultimately affecting behavioural flexibility in each group. We suggest that, even when carnivores and primates would theoretically benefit from the same adaptations with respect to behavioural flexibility, carnivores may nevertheless exhibit less behavioural flexibility than primates because of constraints imposed by past adaptations in the morphology of the limbs and skull. Phylogenetic analysis consistent with this idea suggests greater evolutionary lability in relative brain size within families of primates than carnivores. Thus, consideration of developmental constraints may help elucidate variation in mammalian behavioural flexibility.

  19. Feature Binding in Zebrafish

    Directory of Open Access Journals (Sweden)

    P Neri

    2012-07-01

    Full Text Available Binding operations are primarily ascribed to cortex or similarly complex avian structures. My experiments show that the zebrafish, a lower vertebrate lacking cortex, supports visual feature binding of form and motion for the purpose of social behavior. These results challenge the notion that feature binding may require highly evolved neural structures and demonstrate that the nervous system of lower vertebrates can afford unexpectedly complex computations.

  20. Melanin-binding radiopharmaceuticals

    International Nuclear Information System (INIS)

    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

  1. Competitive protein binding assay

    International Nuclear Information System (INIS)

    Kaneko, Toshio; Oka, Hiroshi

    1975-01-01

    The measurement of cyclic GMP (cGMP) by competitive protein binding assay was described and discussed. The principle of binding assay was represented briefly. Procedures of our method by binding protein consisted of preparation of cGMP binding protein, selection of 3 H-cyclic GMP on market, and measurement procedures. In our method, binding protein was isolated from the chrysalis of silk worm. This method was discussed from the points of incubation medium, specificity of binding protein, the separation of bound cGMP from free cGMP, and treatment of tissue from which cGMP was extracted. cGMP existing in the tissue was only one tenth or one scores of cGMP, and in addition, cGMP competed with cGMP in binding with binding protein. Therefore, Murad's technique was applied to the isolation of cGMP. This method provided the measurement with sufficient accuracy; the contamination by cAMP was within several per cent. (Kanao, N.)

  2. Architecture of cognitive flexibility revealed by lesion mapping

    Science.gov (United States)

    Barbey, Aron K.; Colom, Roberto; Grafman, Jordan

    2013-01-01

    Neuroscience has made remarkable progress in understanding the architecture of human intelligence, identifying a distributed network of brain structures that support goal-directed, intelligent behavior. However, the neural foundations of cognitive flexibility and adaptive aspects of intellectual function remain to be well characterized. Here, we report a human lesion study (n = 149) that investigates the neural bases of key competencies of cognitive flexibility (i.e., mental flexibility and the fluent generation of new ideas) and systematically examine their contributions to a broad spectrum of cognitive and social processes, including psychometric intelligence (Wechsler Adult Intelligence Scale), emotional intelligence (Mayer, Salovey, Caruso Emotional Intelligence Test), and personality (Neuroticism–Extraversion–Openness Personality Inventory). Latent variable modeling was applied to obtain error-free indices of each factor, followed by voxel-based lesion-symptom mapping to elucidate their neural substrates. Regression analyses revealed that latent scores for psychometric intelligence reliably predict latent scores for cognitive flexibility (adjusted R2 = 0.94). Lesion mapping results further indicated that these convergent processes depend on a shared network of frontal, temporal, and parietal regions, including white matter association tracts, which bind these areas into an integrated system. A targeted analysis of the unique variance explained by cognitive flexibility further revealed selective damage within the right superior temporal gyrus, a region known to support insight and the recognition of novel semantic relations. The observed findings motivate an integrative framework for understanding the neural foundations of adaptive behavior, suggesting that core elements of cognitive flexibility emerge from a distributed network of brain regions that support specific competencies for human intelligence. PMID:23721727

  3. Wearable Flexible Sensors: A Review

    KAUST Repository

    Nag, Anindya

    2017-05-18

    The paper provides a review on some of the significant research work done on wearable flexible sensors (WFS). Sensors fabricated with flexible materials have been attached to a person along with the embedded system to monitor a parameter and transfer the significant data to the monitoring unit for further analyses. The use of wearable sensors has played a quite important role to monitor physiological parameters of a person to minimize any malfunctioning happening in the body. The paper categorizes the work according to the materials used for designing the system, the network protocols and different types of activities that were being monitored. The challenges faced by the current sensing systems and future opportunities for the wearable flexible sensors regarding its market values are also briefly explained in the paper.

  4. Wearable Flexible Sensors: A Review

    KAUST Repository

    Nag, Anindya; Mukhopadhyay, Subhas Chandra; Kosel, Jü rgen

    2017-01-01

    The paper provides a review on some of the significant research work done on wearable flexible sensors (WFS). Sensors fabricated with flexible materials have been attached to a person along with the embedded system to monitor a parameter and transfer the significant data to the monitoring unit for further analyses. The use of wearable sensors has played a quite important role to monitor physiological parameters of a person to minimize any malfunctioning happening in the body. The paper categorizes the work according to the materials used for designing the system, the network protocols and different types of activities that were being monitored. The challenges faced by the current sensing systems and future opportunities for the wearable flexible sensors regarding its market values are also briefly explained in the paper.

  5. Living in a Flexible Space

    Science.gov (United States)

    Canepa, Simona

    2017-10-01

    How long does a space or an object have to last? If in the past an object or a building manufacturing was designed to last as much as possible, nowadays it is designed to have a life related to the time in which it will be used. Flexibility is what characterizes a space, it’s the ability to be variable and adaptable to changes in the lives of users or in relation to the use which these will make over time. The evolution of the labour market, the difficulty of inserting within it and the need to push more and more frequent move today in the trial of living space models increasingly flexible: people, especially young people, are forced to move on territory outlining a new condition to which the flexible nomadic dwellings offer an adequate response, ensuring high functional performance in confined spaces.

  6. Balancing energy flexibilities through aggregation

    DEFF Research Database (Denmark)

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

    2014-01-01

    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...... 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 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. FLEXIBLE BUDGET OF SPORT COMPETITIONS

    Directory of Open Access Journals (Sweden)

    Dragan Vukasović

    2009-11-01

    Full Text Available Manager of sport competition has right to decide and also to take responsibility for costs, income and financial results. From economic point of wiev flexible budget and planning cost calculations is top management base for analyzing success level of sport competition. Flexible budget is made before sport competition with few output level, where one is always from static plan-master plan. At the end of competition when we have results, we make report of plan executing and we also analyzing plan variances. Results of comparation between achieved and planning level of static budget can be acceptable if achieved level is approximate to budget level or if we analyzing results from gross or net income. Flexible budget become very important in case of world eco- nomic crises

  8. 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......This volume constitutes the proceedings of the Seventh International Conference on Flexible Query Answering Systems, FQAS 2006, held in Milan, Italy, on June 7--10, 2006. FQAS is the premier conference for researchers and practitioners concerned with the vital task of providing easy, flexible...... are typically equipped with standard query systems which are often inadequate, and the focus of FQAS is the development of query systems that are more expressive, informative, cooperative, and productive. These proceedings contain contributions from invited speakers and 53 original papers out of about 100...

  9. Flexible wings in flapping flight

    Science.gov (United States)

    Moret, Lionel; Thiria, Benjamin; Zhang, Jun

    2007-11-01

    We study the effect of passive pitching and flexible deflection of wings on the forward flapping flight. The wings are flapped vertically in water and are allowed to move freely horizontally. The forward speed is chosen by the flapping wing itself by balance of drag and thrust. We show, that by allowing the wing to passively pitch or by adding a flexible extension at its trailing edge, the forward speed is significantly increased. Detailed measurements of wing deflection and passive pitching, together with flow visualization, are used to explain our observations. The advantage of having a wing with finite rigidity/flexibility is discussed as we compare the current results with our biological inspirations such as birds and fish.

  10. [Flexibility competencies: emotional organization management].

    Science.gov (United States)

    Caballero Muñoz, Domingo; Blanco Prieto, Antonio

    2007-11-01

    The aim of this article is to analyse the transferral of flexibility from contemporary organizations to workers. Through the approach of management by competencies, organizations try to develop in their workers behaviours that are related to efficient job performance. In order to appraise the importance of this approach, we used a critical-rational perspective to discuss the productivity demands that are characteristic of advanced industrial societies. The article shows how the link between workers' flexibility management and their emotional competencies affects their lives, which, like the organizations, should be versatile and adaptable to change.

  11. 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

  12. Development of Flexible Pneumatic Cylinder with Built-in Flexible Linear Encoder and Flexible Bending Sensor

    Science.gov (United States)

    Akagi, Tetsuya; Dohta, Shujiro; Matsushita, Hisashi; Fukuhara, Akimasa

    The purpose of this study is to develop a lightweight and intelligent soft actuator which can be safely attached to the human body. A novel flexible pneumatic cylinder that can be used even if it is deformed by external force had been proposed. The cylinder can realize both pushing and pulling motions even if the cylinder bends. In this paper, a flexible pneumatic cylinder with a built-in flexible linear encoder is proposed and tested. The encoder can detect the cylinder displacement even if the cylinder bends. In the next step, to realize an intelligent flexible cylinder, it is essential to recognize the angle of deflection of the cylinder to estimate the direction of the external force. Therefore, a flexible bending sensor that can measure the directional angle by attaching it to the end of the cylinder is also proposed and tested. The tested bending sensor also consists of four inexpensive photo-reflectors set on the circumferential surface to the cylinder tube every 90 degrees from the center of the tube. By measuring the distance between the photo reflector and the surface of the tube at each point, the bending directional angle of the cylinder can be obtained. A low cost measuring system using a micro-computer incorporating a programmed Up/Down counter to measure the displacement of the cylinder is also developed. As a result, it was confirmed that the measuring accuracy of the bending directional angle was good, less than 0.7 degrees as a standard deviation.

  13. 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.

  14. Application of the random coil index to studying protein flexibility

    Energy Technology Data Exchange (ETDEWEB)

    Berjanskii, Mark V.; Wishart, David S. [University of Alberta, Department of Computing Science (Canada)], E-mail: david.wishart@ualberta.ca

    2008-01-15

    Protein flexibility lies at the heart of many protein-ligand binding events and enzymatic activities. However, the experimental measurement of protein motions is often difficult, tedious and error-prone. As a result, there is a considerable interest in developing simpler and faster ways of quantifying protein flexibility. Recently, we described a method, called Random Coil Index (RCI), which appears to be able to quantitatively estimate model-free order parameters and flexibility in protein structural ensembles using only backbone chemical shifts. Because of its potential utility, we have undertaken a more detailed investigation of the RCI method in an attempt to ascertain its underlying principles, its general utility, its sensitivity to chemical shift errors, its sensitivity to data completeness, its applicability to other proteins, and its general strengths and weaknesses. Overall, we find that the RCI method is very robust and that it represents a useful addition to traditional methods of studying protein flexibility. We have implemented many of the findings and refinements reported here into a web server that allows facile, automated predictions of model-free order parameters, MD RMSF and NMR RMSD values directly from backbone {sup 1}H, {sup 13}C and {sup 15}N chemical shift assignments. The server is available at http: //wishart.biology.ualberta.ca/rcihttp://wishart.biology.ualberta.ca/rci.

  15. Inscription of Behaviour and Flexible Interpretation in Information Infrastructures

    DEFF Research Database (Denmark)

    Henningsson, Stefan; Zinner Henriksen, Helle

    2011-01-01

    Despite the increasing importance of large IT-based solutions binding actors and processes together across institutional borders, still little is known about how these Information Infrastructures (IIs) assume their shapes and potentially may be reshaped towards specific ends. We focus...... on the duality of organizations using the IT artefacts of the European e-Customs IIs to inscribe harmonised behaviour into the operation of the infrastructure and how the IT artefacts are divergently interpreted by the users of the II. We find a tension between the need for artefacts with strong inscription...... to regulate the II and a need for flexibility for II users. The consequence is diluted inscriptions and, in contradiction to what has previously been concluded about interpretative flexibility, the European e-Customs II does not show signs of settling down in a stable phase with consensus. This lack...

  16. Taming Time with Flexible Work.

    Science.gov (United States)

    Stamps, David

    1995-01-01

    Because of increasing incidence of burnout among midlevel managers, many companies are reducing workload schedules, an arrangement that would have been unthinkable 10 years ago. Surveys have made the case that flexible work arrangements increase employee happiness and, therefore, productivity. (JOW)

  17. Flexible working motivates all staff.

    Science.gov (United States)

    2001-04-01

    A recent survey has demolished the myth that work-life balance is only of interest to women with children. The survey, commissioned by Lloyds TSB on behalf of the Employers for Work Life Balance organisation, shows that young workers and men are equally interested in flexible working arrangements that allow them to pursue interests outside of work.

  18. Distribution method optimization : inventory flexibility

    NARCIS (Netherlands)

    Asipko, D.

    2010-01-01

    This report presents the outcome of the Logistics Design Project carried out for Nike Inc. This project has two goals: create a model to measure a flexibility aspect of the inventory usage in different Nike distribution channels, and analyze opportunities of changing the decision model of splitting

  19. 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 ben...

  20. 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.

  1. Requirements for flexible learner monitoring

    NARCIS (Netherlands)

    Glahn, Christian; Specht, Marcus; Koper, Rob

    2007-01-01

    Glahn, C., Specht, M., & Koper, R. (2007). Requirements for flexible learner monitoring. In T. Navarette, J. Blat & R. Koper (Eds.). Proceedings of the 3rd TENCompetence Open Workshop 'Current Research on IMS Learning Design and Lifelong Competence Development Infrastructures' (pp. 89-96). June,

  2. 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)

  3. 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...

  4. 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

  5. Can flexibility help you float?

    Science.gov (United States)

    Burton, L. J.; Bush, J. W. M.

    2012-10-01

    We consider the role of flexibility in the weight-bearing characteristics of bodies floating at an interface. Specifically, we develop a theoretical model for a two-dimensional thin floating plate that yields the maximum stable plate load and optimal stiffness for weight support. Plates small relative to the capillary length are primarily supported by surface tension, and their weight-bearing potential does not benefit from flexibility. Above a critical size comparable to the capillary length, flexibility assists interfacial flotation. For plates on the order of and larger than the capillary length, deflection from an initially flat shape increases the force resulting from hydrostatic pressure, allowing the plate to support a greater load. In this large plate limit, the shape that bears the most weight is a semicircle, which displaces the most fluid above the plate for a fixed plate length. Exact results for maximum weight-bearing plate shapes are compared to analytic approximations made in the limits of large and small plate sizes. The value of flexibility for floating to a number of biological organisms is discussed in light of our study.

  6. Flexible Work Schedules. ERIC Digest.

    Science.gov (United States)

    Kerka, Sandra

    Flexible work schedules are one response to changes in the composition of the work force, new life-styles, and changes in work attitudes. Types of alternative work schedules are part-time and temporary employment, job sharing, and flextime. Part-time workers are a diverse group--women, the very young, and older near-retirees. Although part-time…

  7. Light Management in Flexible OLEDs

    NARCIS (Netherlands)

    Harkema, S.; Pendyala, R.K.; Geurts, C.G.C.; Helgers, P.L.J.; Levell, J.W.; Wilson, J.S.; MacKerron, D.

    2014-01-01

    Organic light-emitting diodes (OLEDs) are a promising lighting technology. In particular OLEDs fabricated on plastic foils are believed to hold the future. These planar devices are subject to various optical losses, which requires sophisticated light management solutions. Flexible OLEDs on plastic

  8. Rationality, decision flexibility and pensions

    NARCIS (Netherlands)

    Koç, Emre

    2015-01-01

    In this thesis several different aspects of the standard economic theory (SET) are examined. One of the premises of the SET is that whether or not an agent has choice flexibility does not influence his behavior. In the first chapter of the thesis we design an experiment to test the validity of this

  9. SHBG (Sex Hormone Binding Globulin)

    Science.gov (United States)

    ... Links Patient Resources For Health Professionals Subscribe Search Sex Hormone Binding Globulin (SHBG) Send Us Your Feedback ... As Testosterone-estrogen Binding Globulin TeBG Formal Name Sex Hormone Binding Globulin This article was last reviewed ...

  10. Mechanisms of zinc binding to the solute-binding protein AztC and transfer from the metallochaperone AztD.

    Science.gov (United States)

    Neupane, Durga P; Avalos, Dante; Fullam, Stephanie; Roychowdhury, Hridindu; Yukl, Erik T

    2017-10-20

    Bacteria can acquire the essential metal zinc from extremely zinc-limited environments by using ATP-binding cassette (ABC) transporters. These transporters are critical virulence factors, relying on specific and high-affinity binding of zinc by a periplasmic solute-binding protein (SBP). As such, the mechanisms of zinc binding and release among bacterial SBPs are of considerable interest as antibacterial drug targets. Zinc SBPs are characterized by a flexible loop near the high-affinity zinc-binding site. The function of this structure is not always clear, and its flexibility has thus far prevented structural characterization by X-ray crystallography. Here, we present intact structures for the zinc-specific SBP AztC from the bacterium Paracoccus denitrificans in the zinc-bound and apo-states. A comparison of these structures revealed that zinc loss prompts significant structural rearrangements, mediated by the formation of a sodium-binding site in the apo-structure. We further show that the AztC flexible loop has no impact on zinc-binding affinity, stoichiometry, or protein structure, yet is essential for zinc transfer from the metallochaperone AztD. We also found that 3 His residues in the loop appear to temporarily coordinate zinc and then convey it to the high-affinity binding site. Thus, mutation of any of these residues to Ala abrogated zinc transfer from AztD. Our structural and mechanistic findings conclusively identify a role for the AztC flexible loop in zinc acquisition from the metallochaperone AztD, yielding critical insights into metal binding by AztC from both solution and AztD. These proteins are highly conserved in human pathogens, making this work potentially useful for the development of novel antibiotics. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. 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...

  12. Flexible devices: from materials, architectures to applications

    Science.gov (United States)

    Zou, Mingzhi; Ma, Yue; Yuan, Xin; Hu, Yi; Liu, Jie; Jin, Zhong

    2018-01-01

    Flexible devices, such as flexible electronic devices and flexible energy storage devices, have attracted a significant amount of attention in recent years for their potential applications in modern human lives. The development of flexible devices is moving forward rapidly, as the innovation of methods and manufacturing processes has greatly encouraged the research of flexible devices. This review focuses on advanced materials, architecture designs and abundant applications of flexible devices, and discusses the problems and challenges in current situations of flexible devices. We summarize the discovery of novel materials and the design of new architectures for improving the performance of flexible devices. Finally, we introduce the applications of flexible devices as key components in real life. Project supported by the National Key R&D Program of China (Nos. 2017YFA0208200, 2016YFB0700600, 2015CB659300), the National Natural Science Foundation of China (Nos. 21403105, 21573108), and the Fundamental Research Funds for the Central Universities (No. 020514380107).

  13. Integrated flexible capacity and inventory management under flexible capacity uncertainty

    OpenAIRE

    Paç, Mehmet Fazıl

    2006-01-01

    Cataloged from PDF version of article. In a manufacturing environment with volatile demand, inventory management can be coupled with dynamic capacity adjustments for handling the fluctuations more effectively. In this study we consider the integrated management of inventory and flexible capacity management under seasonal stochastic demand and uncertain labor supply. The capacity planning problem is investigated from the workforce planning perspective. We consider a manufactu...

  14. Flexible Learning Environments: Leveraging the Affordances of Flexible Delivery and Flexible Learning

    Science.gov (United States)

    Hill, Janette R.

    2006-01-01

    The purpose of this article is to explore the key features of "flexible learning environments" (FLEs). Key principles associated with FLEs are explained. Underlying tenets and support mechanisms necessary for the implementation of FLEs are described. Similarities and differences in traditional learning and FLEs are explored. Finally, strategies…

  15. Graphene-based materials for flexible supercapacitors.

    Science.gov (United States)

    Shao, Yuanlong; El-Kady, Maher F; Wang, Lisa J; Zhang, Qinghong; Li, Yaogang; Wang, Hongzhi; Mousavi, Mir F; Kaner, Richard B

    2015-06-07

    The demand for flexible/wearable electronic devices that have aesthetic appeal and multi-functionality has stimulated the rapid development of flexible supercapacitors with enhanced electrochemical performance and mechanical flexibility. After a brief introduction to flexible supercapacitors, we summarize current progress made with graphene-based electrodes. Two recently proposed prototypes for flexible supercapacitors, known as micro-supercapacitors and fiber-type supercapacitors, are then discussed. We also present our perspective on the development of graphene-based electrodes for flexible supercapacitors.

  16. CARBOHYDRATE-CONTAINING COMPOUNDS WHICH BIND TO CARBOHYDRATE BINDING RECEPTORS

    DEFF Research Database (Denmark)

    1995-01-01

    Carbohydrate-containing compounds which contain saccharides or derivatives thereof and which bind to carbohydrate binding receptors are useful in pharmaceutical products for treatment of inflammatory diseases and other diseases.......Carbohydrate-containing compounds which contain saccharides or derivatives thereof and which bind to carbohydrate binding receptors are useful in pharmaceutical products for treatment of inflammatory diseases and other diseases....

  17. Nonspecific DNA Binding and Bending by HUαβ: Interfaces of the Three Binding Modes Characterized by Salt Dependent Thermodynamics

    Science.gov (United States)

    Koh, Junseock; Shkel, Irina; Saecker, Ruth M.; Record, M. Thomas

    2011-01-01

    Previous ITC and FRET studies demonstrated that Escherichia coli HUαβ binds nonspecifically to duplex DNA in three different binding modes: a tighter-binding 34 bp mode which interacts with DNA in large (>34 bp) gaps between bound proteins, reversibly bending it 140° and thereby increasing its flexibility, and two weaker, modestly cooperative small-site-size modes (10 bp, 6 bp) useful for filling gaps between bound proteins shorter than 34 bp. Here we use ITC to determine the thermodynamics of these binding modes as a function of salt concentration, and deduce that DNA in the 34 bp mode is bent around but not wrapped on the body of HU, in contrast to specific binding of IHF. Analyses of binding isotherms (8, 15, 34 bp DNA) and initial binding heats (34, 38, 160 bp DNA) reveal that all three modes have similar log-log salt concentration derivatives of the binding constants (Ski) even though their binding site sizes differ greatly; most probable values of Ski on 34 bp or larger DNA are − 7.5 ± 0.5. From the similarity of Ski values, we conclude that binding interfaces of all three modes involve the same region of the arms and saddle of HU. All modes are entropy-driven, as expected for nonspecific binding driven by the polyelectrolyte effect. The bent-DNA 34 bp mode is most endothermic, presumably because of the cost of HU-induced DNA bending, while the 6 bp mode is modestly exothermic at all salt concentrations examined. Structural models consistent with the observed Ski values are proposed. PMID:21513716

  18. Two-dimensional flexible nanoelectronics

    Science.gov (United States)

    Akinwande, Deji; Petrone, Nicholas; Hone, James

    2014-12-01

    2014/2015 represents the tenth anniversary of modern graphene research. Over this decade, graphene has proven to be attractive for thin-film transistors owing to its remarkable electronic, optical, mechanical and thermal properties. Even its major drawback--zero bandgap--has resulted in something positive: a resurgence of interest in two-dimensional semiconductors, such as dichalcogenides and buckled nanomaterials with sizeable bandgaps. With the discovery of hexagonal boron nitride as an ideal dielectric, the materials are now in place to advance integrated flexible nanoelectronics, which uniquely take advantage of the unmatched portfolio of properties of two-dimensional crystals, beyond the capability of conventional thin films for ubiquitous flexible systems.

  19. 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.

  20. 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...

  1. 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 ...

  2. Inflation persistence and flexible prices

    OpenAIRE

    Robert Dittmar; William T. Gavin; Finn E. Kydland

    2004-01-01

    If the central bank follows an interest rate rule, then inflation is likely to be persistence, even when prices are fully flexible. Any shock, whether persistent or not, may lead to inflation persistence. In equilibrium, the dynamics of inflation are determined by the evolution of the spread between the real interest rate and the central bank’s target. Inflation persistence in U.S. data can be characterized by a vector autocorrelation function relating inflation and deviations of output from ...

  3. Creating a flexible learning environment.

    Science.gov (United States)

    Taylor, B A; Jones, S; Winters, P

    1990-01-01

    Lack of classroom space is a common problem for many hospital-based nurse educators. This article describes how nursing educators in one institution redesigned fixed classroom space into a flexible learning center that accommodates their various programs. Using the nursing process, the educators assessed their needs, planned the learning environment, implemented changes in the interior design, and evaluated the outcome of the project. The result was a learning environment conducive to teaching and learning.

  4. On Integrity of Flexible Displays

    Science.gov (United States)

    Bouten, Piet C. P.

    Nowadays two display types are dominant in the display market: the bulky cathode ray tube (CRT) and liquid crystal displays (LCD). Both types use glass as substrate material. The LCD display is the dominant player for mobile applications, in for instance mobile phones and portable computers. In the development of displays and their applications a clear interest exists to replace the rigid rectangular display cells by free-shaped, curved or even roll-up cells. These types of applications require flexible displays.

  5. Value of Flexibility - Phase 1

    Science.gov (United States)

    2010-09-25

    010-1 9/25/10 UNCLASSIFIED 99  ― Nike shoes provide flexibility to the customer in terms of color choice, customized emblems (such as college...opportunity, he constructs a synthetic portfolio of a brand -new factory in a developing country, such as China, and bonds. Maybe the monetary values of both...1990s the DoD developed a new guidance kit using a combination of Inertial Navigation (INS) and the satellite based Global Positioning System (GPS

  6. Polar bear hemoglobin and human Hb A0: same 2,3-diphosphoglycerate binding site but asymmetry of the binding?

    Science.gov (United States)

    Pomponi, Massimo; Bertonati, Claudia; Patamia, Maria; Marta, Maurizio; Derocher, Andrew E; Lydersen, Christian; Kovacs, Kit M; Wiig, Oystein; Bårdgard, Astrid J

    2002-11-01

    Polar bear (Ursus maritimus) hemoglobin (Hb) shows a low response to 2,3-diphosphoglycerate (2,3-DPG), compared to human Hb A0, even though these proteins have the same 2,3-DPG-binding site. In addition, polar bear Hb shows a high response to chloride and an alkaline Bohr effect (deltalog P50/deltapH) that is significantly greater than that of human Hb A0. The difference in sequence Pro (Hb A0)-->Gly (polar bear Hb) at position A2 in the A helix seems to be critical for reduced binding of 2,3-DPG. Our results also show that the A2 position may influence not only the flexibility of the A helix, but that differences in flexibility of the first turn of the A helix may affect the unloading of oxygen for the intrinsic ligand affinities of the alpha and beta chains. However, preferential binding to either chain can only take place if there is appreciable asymmetric binding of the phosphoric effector. Regarding this point, 31P NMR data suggest a loss of symmetry of the 2,3-DPG-binding site in the deoxyHb-2,3-DPG complex.

  7. [Flexibility and safety in hospitals].

    Science.gov (United States)

    Fara, G M; Barni, M

    2011-01-01

    The paper explains the reasons according to which the newly-planned hospitals must adopt the concept of advanced flexibility (structural, technological, organizational, diagnostic and therapeutic), in order to avoid the risk of being already obsolete at the moment of their opening, and this due to the fact that too much time elapses in this Country between the moment of planning a new hospital and the moment of the start of its activity. Flexibility is needed at different levels: at low or medium levels for what concerns administrative spaces and also patient rooms (except, in this latter case, when differential intensity of care is adopted); at advanced levelfor what concerns diagnostic and therapeutic areas, which must be rapidly adaptable to new solutions offered by advances in technology and organization. From a different standpoint, flexibility applies also to the fact that hospital must increasingly become a node of a large net including territorial health services: the latter devoted to take care of chronicity, while hospitals should concentrate on acute pathology. Of course the territory surrounding the hospital, through its outpatient service and consultories, is in charge also for first level diagnosy and therapy, leaving the hospital to more sophisticated activities.

  8. 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.

  9. Flexible eddy current coil arrays

    International Nuclear Information System (INIS)

    Krampfner, Y.; Johnson, D.P.

    1987-01-01

    A novel approach was devised to overcome certain limitations of conventional eddy current testing. The typical single-element hand-wound probe was replaced with a two dimensional array of spirally wound probe elements deposited on a thin, flexible polyimide substrate. This provides full and reliable coverage of the test area and eliminates the need for scanning. The flexible substrate construction of the array allows the probes to conform to irregular part geometries, such as turbine blades and tubing, thereby eliminating the need for specialized probes for each geometry. Additionally, the batch manufacturing process of the array can yield highly uniform and reproducible coil geometries. The array is driven by a portable computer-based eddy current instrument, smartEDDY/sup TM/, capable of two-frequency operation, and offers a great deal of versatility and flexibility due to its software-based architecture. The array is coupled to the instrument via an 80-switch multiplexer that can be configured to address up to 1600 probes. The individual array elements may be addressed in any desired sequence, as defined by the software

  10. 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.

  11. Challenges in navigational strategies for flexible endoscopy

    NARCIS (Netherlands)

    van der Stap, N.; van der Heijden, Ferdinand; Broeders, Ivo Adriaan Maria Johannes

    Automating flexible endoscope navigation could lead to an increase in patient safety for endoluminal therapeutic procedures. Additionally, it may decrease the costs of diagnostic flexible endoscope procedures by shortening the learning curve and increasing the efficiency of insertion. Earlier

  12. Soldier Flexible Personal Digital Assistant Program

    National Research Council Canada - National Science Library

    Price, Mark; Woytowich, Jason; Carlson, Marc

    2008-01-01

    The main goal of the Soldier Flexible Personal Digital Assistant Program was to develop prototypes of a novel flexible display technology device for demonstration in a laboratory setting and use in Future Force Warrior (FFW) demonstrations...

  13. Movable MEMS Devices on Flexible Silicon

    KAUST Repository

    Ahmed, Sally

    2013-01-01

    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

  14. 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

  15. UNITY OF THE ORGANIZATIONAL FUNCTIONS FLEXIBILITY

    OpenAIRE

    George MOLDOVEANU; Cosmin DOBRIN

    2012-01-01

    The paper has the goal to analyse the correlation of the flexibility of all organizational functions. Based upon theoretical and practical studies, the decrease of flexibility into an "activity area" of organizations implies a diminution on a large scale of the flexibility of the processing system as a law expression of the decreasing outputs within economy. Therefore, at the level of each organizational function there are several major directions ensuring the flexibility of the "ensemble".

  16. Endogenous price flexibility and optimal monetary policy

    OpenAIRE

    Ozge Senay; Alan Sutherland

    2014-01-01

    Much of the literature on optimal monetary policy uses models in which the degree of nominal price flexibility is exogenous. There are, however, good reasons to suppose that the degree of price flexibility adjusts endogenously to changes in monetary conditions. This article extends the standard new Keynesian model to incorporate an endogenous degree of price flexibility. The model shows that endogenizing the degree of price flexibility tends to shift optimal monetary policy towards complete i...

  17. Flexible learning and the design of instruction

    NARCIS (Netherlands)

    Collis, Betty; Nikolova, Iliana

    1998-01-01

    The paper deals with the problem of designing flexible learning and instruction. Flexibility is considered both from the learner's and the designer's perspective. The potential of telematics in the design, development and implementation of flexible and distance learning is discussed. A Method for

  18. Education, Training and the Flexible Labour Market.

    Science.gov (United States)

    Merson, Martin

    1996-01-01

    The British government's policy of flexible labor market may be interpreted as either flexibility of conditions, which encourages temporary, contingent work, or flexibility of skills, a repertoire that enables workers to undertake a range of tasks as needed. The challenge for educators is to help workers understand and engage in an uncertain world…

  19. 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...... business models will play an important role in ensuring sufficiency and efficiency of flexibility services....

  20. 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…

  1. Cellulose Nanofiber Composite Substrates for Flexible Electronics

    Science.gov (United States)

    Ronald Sabo; Jung-Hun Seo; Zhenqiang Ma

    2012-01-01

    Flexible electronics have a large number of potential applications including malleable displays and wearable computers. The current research into high-speed, flexible electronic substrates employs the use of plastics for the flexible substrate, but these plastics typically have drawbacks, such as high thermal expansion coefficients. Transparent films made from...

  2. 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.

  3. Cellulose binding domain proteins

    Science.gov (United States)

    Shoseyov, Oded; Shpiegl, Itai; Goldstein, Marc; Doi, Roy

    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. Binding and Bulgarian

    NARCIS (Netherlands)

    Schürcks-Grozeva, Lilia Lubomirova

    2003-01-01

    In haar proefschrift analyseert Lilia Schürcks de anaforische verschijnselen in de Bulgaarse taal. Het gaat dan om wederkerende aspecten, uitgedrukt bij woorden als ‘zich’ en ‘elkaar’. De situatie in het Bulgaars blijkt moeilijk in te passen in de klassieke Binding Theory van Noam Chomsky. Bron: RUG

  5. Young children show representational flexibility when interpreting drawings.

    Science.gov (United States)

    Allen, Melissa L; Nurmsoo, Erika; Freeman, Norman

    2016-02-01

    Drawings can be ambiguous and represent more than one entity. In three experiments, we examine whether young children show representational flexibility by allowing one picture to be called by a second name. We also evaluate the hypothesis that children who are representationally flexible see the artist's intention as binding, rather than changeable. In Experiment 1, an artist declared what she intended to draw (e.g. a balloon) but then produced an ambiguous drawing. Children were asked whether the drawings could be interpreted differently (e.g. 'could this be a lollipop?') in the presence of a perceptually similar or dissimilar distractor (e.g., lollipop or snake). Six-year-olds accepted two labels for drawings in both conditions, but four-year-olds only did so in the dissimilar condition. Experiment 2 probed each possible interpretation more deeply by asking property questions (e.g., 'does it float?, does it taste good?'). Preschoolers who understood that the ambiguous drawing could be given two interpretations nevertheless mostly endorsed only properties associated with the prior intent. Experiment 3 provided converging evidence that 4-year-olds were representationally flexible using a paradigm that did not rely upon modal questioning. Taken together, our results indicate that even 4-year-olds understand that pictures may denote more than one referent, they still think of the symbol as consistent with the artist's original intention. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Consumer Central Energy Flexibility in Office Buildings

    DEFF Research Database (Denmark)

    Billanes, Joy Dalmacio; Ma, Zheng; Jørgensen, Bo Nørregaard

    2017-01-01

    Energy flexibility in buildings will play an important role in the smart energy system. Office buildings have more potentials to provide energy flexibility to the grid compared to other types of buildings, due to the existing building management, control systems and large energy consumption....... Consumers in office buildings (building owners/managers and occupants) take a main role for adopting and engaging in building energy flexibility. In this paper provides a systematic review of consumer central energy flexibility in office buildings with the discussion of social, technical and business...... can boost energy flexibility in the office buildings....

  7. Consumer flexibility - State and challenges

    International Nuclear Information System (INIS)

    Grande, Ove S.; Saele, Hanne; Morch, Andrei Z.

    2002-02-01

    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

  8. Functional flexible and wearable supercapacitors

    International Nuclear Information System (INIS)

    Huang, Yan; Zhi, Chunyi

    2017-01-01

    Substantial effort has been devoted to endowing flexible and wearable supercapacitors with desirable functions and solving urgent concerns regarding their practical application, particularly materials selection, air permeability, self-healability, shape memory, integration, and modularization. This gives rise to challenges with regard to both suitable materials and device fabrication. This review highlights the current state-of-the-art of these supercapacitors pertinent to materials, fabrication strategies, and performance. Challenges and solutions are also discussed to further improve their practicality. The aim of this review is to make a timely summary of this emerging field and discuss future opportunities and challenges. (topical review)

  9. Functional flexible and wearable supercapacitors

    Science.gov (United States)

    Huang, Yan; Zhi, Chunyi

    2017-07-01

    Substantial effort has been devoted to endowing flexible and wearable supercapacitors with desirable functions and solving urgent concerns regarding their practical application, particularly materials selection, air permeability, self-healability, shape memory, integration, and modularization. This gives rise to challenges with regard to both suitable materials and device fabrication. This review highlights the current state-of-the-art of these supercapacitors pertinent to materials, fabrication strategies, and performance. Challenges and solutions are also discussed to further improve their practicality. The aim of this review is to make a timely summary of this emerging field and discuss future opportunities and challenges.

  10. Lifelong Open and Flexible Learning

    DEFF Research Database (Denmark)

    Bang, Jørgen

    2006-01-01

    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...... 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....

  11. Flexible Imputation of Missing Data

    CERN Document Server

    van Buuren, Stef

    2012-01-01

    Missing data form a problem in every scientific discipline, yet the techniques required to handle them are complicated and often lacking. One of the great ideas in statistical science--multiple imputation--fills gaps in the data with plausible values, the uncertainty of which is coded in the data itself. It also solves other problems, many of which are missing data problems in disguise. Flexible Imputation of Missing Data is supported by many examples using real data taken from the author's vast experience of collaborative research, and presents a practical guide for handling missing data unde

  12. Novel Flexible Artificial Magnetic Conductor

    Directory of Open Access Journals (Sweden)

    M. E. de Cos

    2012-01-01

    Full Text Available A novel flexible uniplanar AMC design is presented. An AMC prototype is manufactured using laser micromachining and it is characterized under flat and bent conditions by measuring its reflection coefficient phase in an anechoic chamber. The designed prototype shows broad AMC operation bandwidth (6.96% and higher and polarization angle independency. Its angular stability margin, when operating under oblique incidence, is also tested obtaining ±8° as limit for a 14.4 cm × 14.4 cm prototype.

  13. LEARNING ON FLEXIBILITY FROM EXPERIENCES

    DEFF Research Database (Denmark)

    Olsen, Ib Steen; Bonke, Sten

    2011-01-01

    aiming at stimulating the development of new building designs with an improved technological adaptability to new demands and flexibility. The data input to this review is extracted from 15 residential areas with a total of about 1000-1200 apartments which were built in the 1980s after a competition which...... storey housing with cross bearing walls. Within multi storey housing the developed system design appeared to be less adaptable to later alterations. Therefore The Danish Ministry of Housing and Building in 1983 issued an initiative to stimulate technology development of residential non profit housing...

  14. Flexible experimental FPGA based platform

    DEFF Research Database (Denmark)

    Andersen, Karsten Holm; Nymand, Morten

    2016-01-01

    This paper presents an experimental flexible Field Programmable Gate Array (FPGA) based platform for testing and verifying digital controlled dc-dc converters. The platform supports different types of control strategies, dc-dc converter topologies and switching frequencies. The controller platform...... interface supporting configuration and reading of setup parameters, controller status and the acquisition memory in a simple way. The FPGA based platform, provides an easy way within education or research to use different digital control strategies and different converter topologies controlled by an FPGA...

  15. Flexibility in radiation protection legislation

    International Nuclear Information System (INIS)

    Beaver, P.F.; Gill, J.R.

    1980-01-01

    The UK approach to radiation protection legislation is described in detail. The advantages are outlined of a flexible approach whereby the objectives of the legislation are clearly identified but the means of achieving these are left open or qualified by terms such as 'where reasonably practicable'. The roles and viewpoints of management and unions in such an approach are discussed especially with respect to legislation such as the Health and Safety at Work Act. Specific topics include requirements for notification of use, criteria for controlled areas and the tasks of the radiation protection adviser. (UK)

  16. Energy Flexibility in the Power System

    DEFF Research Database (Denmark)

    Billanes, Joy Dalmacio; Ma, Zheng; Jørgensen, Bo Nørregaard

    2017-01-01

    Energy flexibility can address the challenges of large scale integration of renewable energy resources and thereby increasing imbalance in the power system. Flexible power system can provide reliable supply, low electricity cost and sustainability. Various situations and factors influence...... the adoption of the flexibility solutions, such as flexible electricity generation, demand-response, and electricity storage. This paper tries to analyze the current energy flexibility solutions and the factors that can influence the energy flexibility adoption. This paper takes Philippines as case study...... to provide an overview of the current condition of the Philippines’ power system and discuss the energy flexibility in the Philippines’ power system. A further discussion and recommendation is conducted in the end of the paper....

  17. The influence of flexible branches in flexible polymers

    International Nuclear Information System (INIS)

    Wescott, J.T.

    1998-06-01

    In this work the influence of branches in flexible polymer systems has been investigated by consideration of (1) the behaviour of isolated poly-α-olefin chains and (2) the p -T phase behaviour of poly(4-methylpentene-1)(P4MP1). Molecular dynamics simulations of isolated poly-α-olefins were performed in order to gauge directly the effect of molecular structure on chain dimensions, flexibility (via the persistence length) and shape. Under Θ-conditions the addition of short linear branches was shown to increase the flexibility of the backbone. In conditions of good solvent, however, the effect of longer and bulkier branches was to increase the persistence length and average size of the coil with the arrangement of side chain atoms making a small difference. The side branches themselves also affected the solvent conditions experienced by the backbone, behaving much like bound solvent. Consideration of ethylene-α-olefin copolymers, where the branch content was varied from 0-50%, showed that under good solvent conditions the branches increased the chain stiffness only when the gap between side branches was less than five backbone carbon atoms. The backbone torsions were also shown to play an important role in determining these trends. For comparison with the above simulations, persistence length values for polyethylene (= 7.3±0.2A) and P4MP1 (=7.6±0.3A) were measured experimentally by neutron scattering in dilute solution. A value of 6.7±0.5 for the characteristic ratio of PE was also calculated. To investigate the role of a bulky side group in crystalline phases, wide angle X-ray diffraction experiments using a Hikosaka pressure cell were performed on P4MP1. Computer modelling, utilising the experimental data obtained, determined the structure of a disordered phase produced at room temperature and a new high pressure/high temperature phase. The disordered phase was found to be due to a collapse of the backbone combined with some disordering of the side chains

  18. Flexible climate agreements after 2012

    International Nuclear Information System (INIS)

    Vevatne, Jonas

    2004-01-01

    The Kyoto agreement is only a small step towards much stronger and broader commitments and new creativity is needed to further develop a really global climate policy. A flexible approach is necessary to obtain broad participation and substantial reduction of the emissions of greenhouse gases. Flexibility is also important to ease negotiations, to ensure cost-effectiveness and implement a global climate agreement. The US withdrawal from the Kyoto Protocol has rendered the agreement much less effective than the original goal of five per cent reduction of the emission from the industrialized countries. In addition the emissions are increasing much faster in countries that have not committed themselves to the agreement. The agreement runs out in 2012 and should be followed by a new agreement, the negotiations about which are to start up no later than 2005. Attempts by the European Union to begin a discussion about future commitments were very quickly wrecked by the G77 group with strong support from the U.S.A. To formulate a practical climate policy the general goal in the Climate Convention must be interpreted and specified. It may seem impossible to agree upon a long-term goal. But the clarity it provides will be very useful. It will be a guide for short-term goals and a reference for evaluation of success

  19. Flat flexible polymer heat pipes

    International Nuclear Information System (INIS)

    Oshman, Christopher; Li, Qian; Liew, Li-Anne; Yang, Ronggui; Bright, Victor M; Lee, Y C

    2013-01-01

    Flat, flexible, lightweight, polymer heat pipes (FPHP) were fabricated. The overall geometry of the heat pipe was 130 mm × 70 mm × 1.31 mm. A commercially available low-cost film composed of laminated sheets of low-density polyethylene terephthalate, aluminum and polyethylene layers was used as the casing. A triple-layer sintered copper woven mesh served as a liquid wicking structure, and water was the working fluid. A coarse nylon woven mesh provided space for vapor transport and mechanical rigidity. Thermal power ranging from 5 to 30 W was supplied to the evaporator while the device was flexed at 0°, 45° and 90°. The thermal resistance of the FPHP ranged from 1.2 to 3.0 K W −1 depending on the operating conditions while the thermal resistance for a similar-sized solid copper reference was a constant at 4.6 K W −1 . With 25 W power input, the thermal resistance of the liquid–vapor core of the FPHP was 23% of a copper reference sample with identical laminated polymer material. This work shows a promising combination of technologies that has the potential to usher in a new generation of highly flexible, lightweight, low-cost, high-performance thermal management solutions. (paper)

  20. Superhydrophobicity enhancement through substrate flexibility

    Science.gov (United States)

    Vasileiou, Thomas; Gerber, Julia; Prautzsch, Jana; Schutzius, Thomas; Poulikakos, Dimos

    2017-11-01

    Inspired by manifestations in nature, micro/nanoengineering superhydrophobic surfaces has been the focus of much work. Generally, hydrophobicity is increased through the combined effects of surface texturing and chemistry; being durable, rigid substrate materials are the norm. However, many natural and technical materials are flexible, and the resulting effect on hydrophobicity has been largely unexplored. Here, we show that the rational tuning of flexibility can work collaboratively with the surface micro/nanotexture to enhance liquid repellency performance, defined by impalement and breakup resistance, contact time reduction, and restitution coefficient increase. Reduction in substrate stiffness and areal density imparts immediate acceleration and intrinsic responsiveness to impacting droplets, mitigating the collision and lowering the impalement probability by 60 % without the need for active actuation. We demonstrate the above discoveries with materials ranging from thin steel or polymer sheets to butterfly wings. Partial support of the Swiss National Science Foundation under Grant 162565 and the European Research Council under Advanced Grant 669908 (INTICE) is acknowledged.

  1. Flexible thin film magnetoimpedance sensors

    International Nuclear Information System (INIS)

    Kurlyandskaya, G.V.; Fernández, E.; Svalov, A.; Burgoa Beitia, A.; García-Arribas, A.; Larrañaga, A.

    2016-01-01

    Magnetically soft thin film deposited onto polymer substrates is an attractive option for flexible electronics including magnetoimpedance (MI) applications. MI FeNi/Ti based thin film sensitive elements were designed and prepared using the sputtering technique by deposition onto rigid and flexible substrates at different deposition rates. Their structure, magnetic properties and MI were comparatively analyzed. The main structural features were sufficiently accurately reproduced in the case of deposition onto cyclo olefine polymer substrates compared to glass substrates for the same conditions. Although for the best condition (28 nm/min rate) of the deposition onto polymer a significant reduction of the MI field sensitivity was found satisfactory for sensor applications sensitivity: 45%/Oe was obtained for a frequency of 60 MHz. - Highlights: • [FeNi/Ti] 3 /Cu/[FeNi/Ti] 3 films were prepared by sputtering at different deposition rates. • Polymer substrates insure sufficiently accurate reproducibility of the film structure. • High deposition rate of 28 nm/min insures the highest values of the magnetoimpedance sensitivity. • Deposition onto polymer results in the satisfactory magnetoimpedance sensitivity of 45%/Oe.

  2. Flexible thin film magnetoimpedance sensors

    Energy Technology Data Exchange (ETDEWEB)

    Kurlyandskaya, G.V., E-mail: galina@we.lc.ehu.es [Universidad del País Vasco, UPV/EHU, Departamento de Electricidad y Electrónica, P.O. Box 644, Bilbao 48080 (Spain); Ural Federal University, Laboratory of Magnetic sensoric, Lenin Ave. 51, 620083 Ekaterinburg (Russian Federation); Fernández, E. [BCMaterials UPV-EHU, Vizcaya Science and Technology Park, 48160 Derio (Spain); Svalov, A. [Universidad del País Vasco, UPV/EHU, Departamento de Electricidad y Electrónica, P.O. Box 644, Bilbao 48080 (Spain); Ural Federal University, Laboratory of Magnetic sensoric, Lenin Ave. 51, 620083 Ekaterinburg (Russian Federation); Burgoa Beitia, A. [Universidad del País Vasco, UPV/EHU, Departamento de Electricidad y Electrónica, P.O. Box 644, Bilbao 48080 (Spain); García-Arribas, A. [Universidad del País Vasco, UPV/EHU, Departamento de Electricidad y Electrónica, P.O. Box 644, Bilbao 48080 (Spain); BCMaterials UPV-EHU, Vizcaya Science and Technology Park, 48160 Derio (Spain); Larrañaga, A. [SGIker, Servicios Generales de Investigación, Universidad del País Vasco (UPV/EHU), 48080 Bilbao (Spain)

    2016-10-01

    Magnetically soft thin film deposited onto polymer substrates is an attractive option for flexible electronics including magnetoimpedance (MI) applications. MI FeNi/Ti based thin film sensitive elements were designed and prepared using the sputtering technique by deposition onto rigid and flexible substrates at different deposition rates. Their structure, magnetic properties and MI were comparatively analyzed. The main structural features were sufficiently accurately reproduced in the case of deposition onto cyclo olefine polymer substrates compared to glass substrates for the same conditions. Although for the best condition (28 nm/min rate) of the deposition onto polymer a significant reduction of the MI field sensitivity was found satisfactory for sensor applications sensitivity: 45%/Oe was obtained for a frequency of 60 MHz. - Highlights: • [FeNi/Ti]{sub 3}/Cu/[FeNi/Ti]{sub 3} films were prepared by sputtering at different deposition rates. • Polymer substrates insure sufficiently accurate reproducibility of the film structure. • High deposition rate of 28 nm/min insures the highest values of the magnetoimpedance sensitivity. • Deposition onto polymer results in the satisfactory magnetoimpedance sensitivity of 45%/Oe.

  3. Light management in flexible OLEDs

    Science.gov (United States)

    Harkema, Stephan; Pendyala, Raghu K.; Geurts, Christian G. C.; Helgers, Paul L. J.; Levell, Jack W.; Wilson, Joanne S.; MacKerron, Duncan

    2014-10-01

    Organic light-emitting diodes (OLEDs) are a promising lighting technology. In particular OLEDs fabricated on plastic foils are believed to hold the future. These planar devices are subject to various optical losses, which requires sophisticated light management solutions. Flexible OLEDs on plastic substrates are as prone to losses related to wave guiding as devices on glass. However, we determined that OLEDs on plastic substrates are susceptible to another loss mode due to wave guiding in the thin film barrier. With modeling of white polymer OLEDs fabricated on PEN substrates, we demonstrate that this loss mode is particularly sensitive to polarized light emission. Furthermore, we investigated how thin film barrier approaches can be combined with high index light extraction layers. Our analysis shows that OLEDs with a thin film barrier consisting of an inorganic/organic/inorganic layer sequence, a low index inorganic negatively affects the OLED efficiency. We conclude that high index inorganics are more suitable for usage in high efficiency flexible OLEDs.

  4. Binding-site assessment by virtual fragment screening.

    Directory of Open Access Journals (Sweden)

    Niu Huang

    2010-04-01

    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.

  5. On the concept of flexibility: A dual control perspective

    NARCIS (Netherlands)

    A.C.J. de Leeuw (A. C J); H.W. Volberda (Henk)

    1996-01-01

    textabstractOrganizational flexibility has recently received much attention from researchers, management consultants and practitioners. In general, the term 'flexibility' has a positive connotation: flexible organizations are the better ones. However, the meaning of flexibility as well as its

  6. On the concept of flexibility : A dual control perspective

    NARCIS (Netherlands)

    de Leeuw, A.C.J.; Volberda, H.W.

    Organizational flexibility has recently received much attention from researchers, management consultants and practitioners, In general, the term 'flexibility' has a positive connotation: flexible organizations are the better ones. However, the meaning of flexibility as well as its relation to the

  7. 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.

  8. 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

    2013-01-01

    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. PMID:23881402

  9. Functional Advantages of Conserved Intrinsic Disorder in RNA-Binding Proteins

    OpenAIRE

    Varadi, Mihaly; Zsolyomi, Fruzsina; Guharoy, Mainak; Tompa, Peter

    2015-01-01

    Proteins form large macromolecular assemblies with RNA that govern essential molecular processes. RNA-binding proteins have often been associated with conformational flexibility, yet the extent and functional implications of their intrinsic disorder have never been fully assessed. Here, through large-scale analysis of comprehensive protein sequence and structure datasets we demonstrate the prevalence of intrinsic structural disorder in RNA-binding proteins and domains. We addressed their func...

  10. Long chain fatty acids alter the interactive binding of ligands to the two principal drug binding sites of human serum albumin.

    Directory of Open Access Journals (Sweden)

    Keishi Yamasaki

    Full Text Available A wide variety of drugs bind to human serum albumin (HSA at its two principal sites, namely site I and site II. A number of reports indicate that drug binding to these two binding sites are not completely independent, and that interactions between ligands of these two discrete sites can play a role. In this study, the effect of the binding of long-chain fatty acids on the interactive binding between dansyl-L-asparagine (DNSA; site I ligand and ibuprofen (site II ligand at pH6.5 was examined. Binding experiments showed that the binding of sodium oleate (Ole to HSA induces conformational changes in the molecule, which, in turn, changes the individual binding of DNSA and ibuprofen, as well as the mode of interaction between these two ligands from a 'competitive-like' allosteric interaction in the case of the defatted HSA conformer to a 'nearly independent' binding in the case of non-defatted HSA conformer. Circular dichroism measurements indicated that ibuprofen and Ole are likely to modify the spatial orientation of DNSA at its binding site. Docking simulations suggest that the long-distance electric repulsion between DNSA and ibuprofen on defatted HSA contributes to a 'competitive-like' allosteric interaction, whereas extending the distance between ligands and/or increasing the flexibility or size of the DNSA binding site in fatted HSA evokes a change in the interaction mode to 'nearly independent' binding. The present findings provide further insights into the structural dynamics of HSA upon the binding of fatty acids, and its effects on drug binding and drug-drug interactions that occur on HSA.

  11. The necessity of connection structures in neural models of variable binding.

    Science.gov (United States)

    van der Velde, Frank; de Kamps, Marc

    2015-08-01

    In his review of neural binding problems, Feldman (Cogn Neurodyn 7:1-11, 2013) addressed two types of models as solutions of (novel) variable binding. The one type uses labels such as phase synchrony of activation. The other ('connectivity based') type uses dedicated connections structures to achieve novel variable binding. Feldman argued that label (synchrony) based models are the only possible candidates to handle novel variable binding, whereas connectivity based models lack the flexibility required for that. We argue and illustrate that Feldman's analysis is incorrect. Contrary to his conclusion, connectivity based models are the only viable candidates for models of novel variable binding because they are the only type of models that can produce behavior. We will show that the label (synchrony) based models analyzed by Feldman are in fact examples of connectivity based models. Feldman's analysis that novel variable binding can be achieved without existing connection structures seems to result from analyzing the binding problem in a wrong frame of reference, in particular in an outside instead of the required inside frame of reference. Connectivity based models can be models of novel variable binding when they possess a connection structure that resembles a small-world network, as found in the brain. We will illustrate binding with this type of model with episode binding and the binding of words, including novel words, in sentence structures.

  12. 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...

  13. Retrofitting for fossil fuel flexibility

    International Nuclear Information System (INIS)

    Newell, J.; Trueblood, R.C.; Lukas, R.W.; Worster, C.M.; Marx, P.D.

    1991-01-01

    Described in this paper are two fossil plant retrofits recently completed by the Public Service Company of New Hampshire that demonstrate the type of planning and execution required for a successful project under the current regulatory and budget constraints. Merrimack Units 1 and 2 are 120 MW and 338 MW nominal cyclone-fired coal units in Bow, New Hampshire. The retrofits recently completed at these plants have resulted in improved particulate emissions compliance, and the fuel flexibility to allow switching to lower sulphur coals to meet current and future SO 2 emission limits. Included in this discussion are the features of each project including the unique precipitator procurement approach for the Unit 1 Retrofit, and methods used to accomplish both retrofits within existing scheduled maintenance outages through careful planning and scheduling, effective use of pre-outage construction, 3-D CADD modeling, modular construction and early procurement. Operating experience while firing various coals in the cyclone fired boilers is also discussed

  14. International Expansion through Flexible Replication

    DEFF Research Database (Denmark)

    Jonsson, Anna; Foss, Nicolai Juul

    2011-01-01

    Business organizations may expand internationally by replicating a part of their value chain, such as a sales and marketing format, in other countries. However, little is known regarding how such “international replicators” build a format for replication, or how they can adjust it in order to ada......, etc.) are replicated in a uniform manner across stores, and change only very slowly (if at all) in response to learning (“flexible replication”). We conclude by discussing the factors that influence the approach to replication adopted by an international replicator.......Business organizations may expand internationally by replicating a part of their value chain, such as a sales and marketing format, in other countries. However, little is known regarding how such “international replicators” build a format for replication, or how they can adjust it in order to adapt...

  15. Security and labour market flexibility

    DEFF Research Database (Denmark)

    Refslund, Bjarke; Rasmussen, Stine; Sørensen, Ole H.

    2017-01-01

    In the face of the economic and financial crisis, several European countries have implemented a number of structural reforms to increase employment and the flexibility of the labour market, in particular by reducing employment protection in an effort to deregulate labour markets. Reform proponents...... employment. Conversely, reform opponents claim that this view builds on a misguided view of labour market dynamics. They do not believe that such reforms will lead to job growth, asserting that such reforms are as likely to reduce as to increase employment and that they will lead to growing inequality...... and labour market segmentation. In Denmark, employee protection in terms of notice periods and dismissal compensation, which is mainly regulated by collective agreement, is among the lowest in the EU. Unemployment was, before the crisis, among the lowest in the EU but the crisis also negatively affected...

  16. 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...

  17. Bio-Inspired Flexible Cellular Actuating Systems

    Science.gov (United States)

    2013-11-21

    S. Hong, “Robust adaptive boundary control of a flexible marine riser with vessel dynamics,” Automatica, vol. 47, pp. 722–732, 2011. [22] D. H...conditionally accepted. [6] W. He, S. S. Ge, B. V. E. How, Y. S. Choo, and K. S. Hong, “Robust adaptive boundary control of a flexible marine riser ... flexible robotic actuators, often represented by a distributed parameter system or a partial differential equation. We establish a model-guided

  18. 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.

  19. Flexible benefit plans in Dutch organisations

    OpenAIRE

    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 employees a choice in the way they are paid, employers hoped to become more attractive employers, and lend a helping hand to employees who were combining work and care. In this study, flexible benefit p...

  20. Labor Supply Flexibility and Portfolio Choice

    OpenAIRE

    Zvi Bodie; William Samuelson

    1989-01-01

    This paper develops a model showing that people who have flexibility in choosing how much to work will prefer to invest substantially more of their money in risky assets than if they had no such flexibility. Viewed in this way, labor supply flexibility offers insurance against adverse investment outcomes. The model provides support for the conventional wisdom that the young can tolerate more risk in their investment portfolios than the old. The model has other implications for the study of ho...

  1. 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.

  2. Processes and Materials for Flexible PV Arrays

    National Research Council Canada - National Science Library

    Gierow, Paul

    2002-01-01

    .... A parallel incentive for development of flexible PV arrays are the possibilities of synergistic advantages for certain types of spacecraft, in particular the Solar Thermal Propulsion (STP) Vehicle...

  3. Flexible UAV Mission Management Using Emerging Technologies

    National Research Council Canada - National Science Library

    Desimone, Roberto; Lee, Richard

    2002-01-01

    This paper discusses recent results and proposed work in the application of emerging artificial intelligence technologies for flexible mission management, especially for unmanned (combat) airborne vehicles...

  4. 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.

  5. Reflection-Based Python-C++ Bindings

    International Nuclear Information System (INIS)

    Generowicz, Jacek; Lavrijsen, Wim T.L.P.; Marino, Massimo; Mato, Pere

    2004-01-01

    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

  6. Optical Binding of Nanowires

    Czech Academy of Sciences Publication Activity Database

    Simpson, Stephen Hugh; Zemánek, Pavel; Marago, O.M.; Jones, P.H.; Hanna, S.

    2017-01-01

    Roč. 17, č. 6 (2017), s. 3485-3492 ISSN 1530-6984 R&D Projects: GA ČR GB14-36681G Grant - others:AV ČR(CZ) CNR-16-12 Program:Bilaterální spolupráce Institutional support: RVO:68081731 Keywords : optical binding nanowires * Brownian motion * self-organization * non-equilibrium thermodynamics * non-equilibrium steady state * spin-orbit coupling * emergent phenomena Subject RIV: BH - Optics, Masers, Lasers OBOR OECD: Optics (including laser optics and quantum optics) Impact factor: 12.712, year: 2016

  7. THE FLEXIBILITY-AUTOMATION CORRESPONDENCE TO A VIRTUAL COMMERCIAL SOCIETY

    Directory of Open Access Journals (Sweden)

    Liliana Doble

    2012-01-01

    Full Text Available Design and operation of FMS is based on system requirement can be as productive and flexible as necessary, i.e. obtaining controlled correspondence between the degree of flexibility and automation of system.The flexibility of a FMS (Flexible Manufacturing Systems is determined by two important criteria: Flexible hardware structure of the system; Flexible software structure. Flexible hardware structure of the CS system (calculation system is determined to its turn according to three components: Flexibility of technological subsystem; Flexibility subsystem of storage, transport and handling;Flexibility of informational subsystem.

  8. 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

  9. Dynamic Model of a Rotating Flexible Arm-Flexible Root Mechanism Driven by a Shaft Flexible in Torsion

    Directory of Open Access Journals (Sweden)

    S.Z. Ismail

    2006-01-01

    Full Text Available This paper presents a dynamic model of a rotating flexible beam carrying a payload at its tip. The model accounts for the driving shaft and the arm root flexibilities. The finite element method and the Lagrangian dynamics are used in deriving the equations of motion with the small deformation theory assumptions and the Euler-Bernoulli beam theory. The obtained model is a nonlinear-coupled system of differential equations. The model is simulated for different combinations of shaft and root flexibilities and arm properties. The simulation results showed that the root flexibility is an important factor that should be considered in association with the arm and shaft flexibilities, as its dynamics influence the motor motion. Moreover, the effect of system non-linearity on the dynamic behavior is investigated by simulating the equivalent linearized system and it was found to be an important factor that should be considered, particularly when designing a control strategy for practical implementation.

  10. Electrostatics and Flexibility Drive Membrane Recognition and Early Penetration by Antimicrobial Peptide Dendrimer bH1

    Energy Technology Data Exchange (ETDEWEB)

    Ravi, Harish Kumar; Stach, Michaela; Soares, Thereza A.; Darbre, Tamis; Reymond, Jean-Louis; Cascella, Michele

    2013-08-01

    Molecular dynamics simulation of polycationic antimicrobial peptide dendrimer bH1 (Leu)8(DapLeu)4(DapPhe)2DapLys- NH2 binding to membranes suggest that electrostatic 10 interactions with the polyanionic lipopolysaccharide (LPS) and conformational flexibility of the 2,3-diaminopropanoic acid (Dap) branching units drive its selective insertion into microbial membranes.

  11. Understanding the physical and chemical nature of the warfarin drug binding site in human serum albumin: experimental and theoretical studies.

    Science.gov (United States)

    Abou-Zied, Osama K

    2015-01-01

    Human serum albumin (HSA) is one of the major carrier proteins in the body and constitutes approximately half of the protein found in blood plasma. It plays an important role in lipid metabolism, and its ability to reversibly bind a large variety of pharmaceutical compounds makes it a crucial determinant of drug pharmacokinetics and pharmacodynamics. This review deals with one of the protein's major binding sites "Sudlow I" which includes a binding pocket for the drug warfarin (WAR). The binding nature of this important site can be characterized by measuring the spectroscopic changes when a ligand is bound. Using several drugs, including WAR, and other drug-like molecules as ligands, the results emphasize the nature of Sudlow I as a flexible binding site, capable of binding a variety of ligands by adapting its binding pockets. The high affinity of the WAR pocket for binding versatile molecular structures stems from the flexibility of the amino acids forming the pocket. The binding site is shown to have an ionization ability which is important to consider when using drugs that are known to bind in Sudlow I. Several studies point to the important role of water molecules trapped inside the binding site in molecular recognition and ligand binding. Water inside the protein's cavity is crucial in maintaining the balance between the hydrophobic and hydrophilic nature of the binding site. Upon the unfolding and refolding of HSA, more water molecules are trapped inside the binding site which cause some swelling that prevents a full recovery from the denatured state. Better understanding of the mechanism of binding in macromolecules such as HSA and other proteins can be achieved by combining experimental and theoretical studies which produce significant synergies in studying complex biochemical phenomena.

  12. Exploiting protein flexibility to predict the location of allosteric sites

    Directory of Open Access Journals (Sweden)

    Panjkovich Alejandro

    2012-10-01

    Full Text Available Abstract Background Allostery is one of the most powerful and common ways of regulation of protein activity. However, for most allosteric proteins identified to date the mechanistic details of allosteric modulation are not yet well understood. Uncovering common mechanistic patterns underlying allostery would allow not only a better academic understanding of the phenomena, but it would also streamline the design of novel therapeutic solutions. This relatively unexplored therapeutic potential and the putative advantages of allosteric drugs over classical active-site inhibitors fuel the attention allosteric-drug research is receiving at present. A first step to harness the regulatory potential and versatility of allosteric sites, in the context of drug-discovery and design, would be to detect or predict their presence and location. In this article, we describe a simple computational approach, based on the effect allosteric ligands exert on protein flexibility upon binding, to predict the existence and position of allosteric sites on a given protein structure. Results By querying the literature and a recently available database of allosteric sites, we gathered 213 allosteric proteins with structural information that we further filtered into a non-redundant set of 91 proteins. We performed normal-mode analysis and observed significant changes in protein flexibility upon allosteric-ligand binding in 70% of the cases. These results agree with the current view that allosteric mechanisms are in many cases governed by changes in protein dynamics caused by ligand binding. Furthermore, we implemented an approach that achieves 65% positive predictive value in identifying allosteric sites within the set of predicted cavities of a protein (stricter parameters set, 0.22 sensitivity, by combining the current analysis on dynamics with previous results on structural conservation of allosteric sites. We also analyzed four biological examples in detail, revealing

  13. Quantifying the topography of the intrinsic energy landscape of flexible biomolecular recognition

    Science.gov (United States)

    Chu, Xiakun; Gan, Linfeng; Wang, Erkang; Wang, Jin

    2013-01-01

    Biomolecular functions are determined by their interactions with other molecules. Biomolecular recognition is often flexible and associated with large conformational changes involving both binding and folding. However, the global and physical understanding for the process is still challenging. Here, we quantified the intrinsic energy landscapes of flexible biomolecular recognition in terms of binding–folding dynamics for 15 homodimers by exploring the underlying density of states, using a structure-based model both with and without considering energetic roughness. By quantifying three individual effective intrinsic energy landscapes (one for interfacial binding, two for monomeric folding), the association mechanisms for flexible recognition of 15 homodimers can be classified into two-state cooperative “coupled binding–folding” and three-state noncooperative “folding prior to binding” scenarios. We found that the association mechanism of flexible biomolecular recognition relies on the interplay between the underlying effective intrinsic binding and folding energy landscapes. By quantifying the whole global intrinsic binding–folding energy landscapes, we found strong correlations between the landscape topography measure Λ (dimensionless ratio of energy gap versus roughness modulated by the configurational entropy) and the ratio of the thermodynamic stable temperature versus trapping temperature, as well as between Λ and binding kinetics. Therefore, the global energy landscape topography determines the binding–folding thermodynamics and kinetics, crucial for the feasibility and efficiency of realizing biomolecular function. We also found “U-shape” temperature-dependent kinetic behavior and a dynamical cross-over temperature for dividing exponential and nonexponential kinetics for two-state homodimers. Our study provides a unique way to bridge the gap between theory and experiments. PMID:23754431

  14. Cloud flexibility using DIRAC interware

    International Nuclear Information System (INIS)

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

    2014-01-01

    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

  15. 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

  16. 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

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

    NARCIS (Netherlands)

    Berkhout, E.; Heyma, A.; Prins, J.

    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

  18. Flexible Metal Oxide/Graphene Oxide Hybrid Neuromorphic Devices on Flexible Conducting Graphene Substrates

    OpenAIRE

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

    2016-01-01

    Flexible metal oxide/graphene oxide hybrid multi-gate neuron transistors were fabricated on flexible graphene substrates. Dendritic integrations in both spatial and temporal modes were successfully emulated, and spatiotemporal correlated logics were obtained. A proof-of-principle visual system model for emulating lobula giant motion detector neuron was investigated. Our results are of great interest for flexible neuromorphic cognitive systems.

  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. 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....

  1. Harnessing Flexibility from Hot and Cold

    DEFF Research Database (Denmark)

    Kiviluoma, Juha; Heinen, Steve; Qazi, Hassan

    2017-01-01

    As has been often reported, electricity systems with high levels of variable wind and solar power generation would benefit from demand flexibility. What is not as often mentioned is that electrification of the transport and heat sectors could exacerbate the need for flexibility, if they are imple...

  2. 47 CFR 1.774 - Pricing flexibility.

    Science.gov (United States)

    2010-10-01

    ... copies shall be served upon the Chief, Wireline Competition Bureau and the Chief, Pricing Policy Division... 47 Telecommunication 1 2010-10-01 2010-10-01 false Pricing flexibility. 1.774 Section 1.774..., and Reports Involving Common Carriers Tariffs § 1.774 Pricing flexibility. (a) Petitions. (1) A...

  3. Cognitive Flexibility in Drawings of Bilingual Children

    Science.gov (United States)

    Adi-Japha, Esther; Berberich-Artzi, Jennie; Libnawi, Afaf

    2010-01-01

    A. Karmiloff-Smith's (1990) task of drawing a nonexistent object is considered to be a measure of cognitive flexibility. The notion of earlier emergence of cognitive flexibility in bilingual children motivated the current researchers to request 4- and 5-year-old English-Hebrew and Arabic-Hebrew bilingual children and their monolingual peers to…

  4. New business model of flexible housing

    NARCIS (Netherlands)

    Zairul, Z.; Geraedts, R.P.

    2015-01-01

    The Open Building (OB) and the concept of flexible housing has alwaysassociated with user’s ability to respond to changing demand. It is necessary that housing can adap to changing market conditions and different users’ requirements. Flexibility makes a crucial concept that one cannot ignore.

  5. The Flexibility of Pusher Furnace Grate

    Directory of Open Access Journals (Sweden)

    Słowik J.A.

    2016-12-01

    Full Text Available The lifetime of guide grates in pusher furnaces for heat treatment could be increased by raising the flexibility of their structure through, for example, the replacement of straight ribs, parallel to the direction of grate movement, with more flexible segments. The deformability of grates with flexible segments arranged in two orientations, i.e. crosswise (perpendicular to the direction of compression and lengthwise (parallel to the direction of compression, was examined. The compression process was simulated using SolidWorks Simulation program. Relevant regression equations were also derived describing the dependence of force inducing the grate deformation by 0.25 mm ‒ modulus of grate elasticity ‒ on the number of flexible segments in established orientations. These calculations were made in Statistica and Scilab programs. It has been demonstrated that, with the same number of segments, the crosswise orientation of flexible segments increases the grate structure flexibility in a more efficient way than the lengthwise orientation. It has also been proved that a crucial effect on the grate flexibility has only the quantity and orientation of segments (crosswise / lengthwise, while the exact position of segments changes the grate flexibility by less than 1%.

  6. Working Hours Flexibility. Background Paper No. 30.

    Science.gov (United States)

    Staines, Graham L.

    Flexible work schedules offer the promise of a low-cost option for helping people manage work and family responsibilities. Alternative work schedules include part-time work, job sharing, work sharing, shiftwork, compressed work week, flexitime, and flexiplace. Flexitime is the most prevalent full-time flexible schedule and is second in prevalence…

  7. High-flexibility, noncollapsing lightweight hose

    Science.gov (United States)

    Williams, D.A.

    1993-04-20

    A high-flexibility, noncollapsing, lightweight, large-bore, wire-reinforced hose is inside fiber-reinforced PVC tubing that is flexible, lightweight, and abrasion resistant. It provides a strong, kink- and collapse-free conduit for moving large quantities of dangerous fluids, e.g., removing radioactive waste water or processing chemicals.

  8. Flexible Learning in an Information Society

    Science.gov (United States)

    Khan, Badrul, Ed.

    2007-01-01

    Flexible Learning in an Information Society uses a flexible learning framework to explain the best ways of creating a meaningful learning environment. This framework consists of eight factors--institutional, management, technological, pedagogical, ethical, interface design, resource support, and evaluation--and a systematic understanding of these…

  9. Flexible job shop scheduling problem in manufacturing

    OpenAIRE

    Curralo, Ana; Pereira, Ana I.; Barbosa, José; Leitão, Paulo

    2013-01-01

    This paper addresses a real assembly cell: the AIP-PRIMECA cell at the Université de Valenciennes et du Hainaut-Cambrésis, in France. This system can be viewed as a Flexible Job Shop, leading to the formulation of a Flexible Job Shop Scheduling Problem (FJSSP).

  10. Flexible protective gloves: The emperor's new clothes

    International Nuclear Information System (INIS)

    Kelsey, C.A.; Mettler, F.A. Jr.

    1990-01-01

    The risk of developing skin cancer is estimated for interventional radiologists who do and do not wear thin, flexible protective leaded gloves. The use of these gloves is extremely expensive in terms of dollars per potential cancer prevented. Good radiographic practice without the use of flexible protective gloves provides adequate protection

  11. Quality and workflow integration in flexible manufacturing

    NARCIS (Netherlands)

    ten Dam, Dennis

    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

  12. 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

  13. Operational Flexibility Responses to Environmental Uncertainties

    OpenAIRE

    Miller, Kent D.

    1994-01-01

    This study develops and tests a behavioral model of organizational changes in operational flexibility. Regression results using an international data set provide strong support for the general proposition that uncertainties associated with different environmental components--poitical, government policy, macroeconomic, competitive, input and product demand uncertainties--have different implications for firm internal, locational, and supploer flexibility. Slack acts as a buffer attenuating, a...

  14. 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

  15. Studies of a flexible heliac configuration

    International Nuclear Information System (INIS)

    Hender, T.C.; Cantrell, J.L.; Harris, J.H.

    1987-07-01

    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

  16. 77 FR 8082 - Regulatory Flexibility Agenda

    Science.gov (United States)

    2012-02-13

    ... Required: Yes. Agency Contact: Alicia Goldin, Division of Trading and Markets, Securities and Exchange.../01/11 Regulatory Flexibility Analysis Required: Yes. Agency Contact: Alicia Goldin, Division of... Withdrawn 10/01/11 Regulatory Flexibility Analysis Required: Yes. Agency Contact: Alicia Goldin, Division of...

  17. Substitution effect and effect of axle’s flexibility at (pseudo-rotaxanes

    Directory of Open Access Journals (Sweden)

    Friedrich Malberg

    2014-06-01

    Full Text Available This study investigates the effect of substitution with different functional groups and of molecular flexibility by changing within the axle from a single C–C bond to a double C=C bond. Therefore, we present static quantum chemical calculations at the dispersion-corrected density functional level (DFT-D3 for several Leigh-type rotaxanes. The calculated crystal structure is in close agreement with the experimental X-ray data. Compared to a stiffer axle, a more flexible one results in a stronger binding by 1–3 kcal/mol. Alterations of the binding energy in the range of 5 kcal/mol could be achieved by substitution with different functional groups. The hydrogen bond geometry between the isophtalic unit and the carbonyl oxygen atoms of the axle exhibited distances in the range of 2.1 to 2.4 Å for six contact points, which shows that not solely but to a large amount the circumstances in the investigated rotaxanes are governed by hydrogen bonding. Moreover, the complex with the more flexible axle is usually more unsymmetrical than the one with the stiff axle. The opposite is observed for the experimentally investigated axle with the four phenyl stoppers. Furthermore, we considered an implicit continuum solvation model and found that the complex binding is weakened by approximately 10 kcal/mol, and hydrogen bonds are slightly shortened (by up to 0.2 Å.

  18. Smart Tendon Actuated Flexible Actuator

    Directory of Open Access Journals (Sweden)

    Md. Masum Billah

    2015-01-01

    Full Text Available We investigate the kinematic feasibility of a tendon-based flexible parallel platform actuator. Much of the research on tendon-driven Stewart platforms is devoted either to the completely restrained positioning mechanism (CRPM or to one particular type of the incompletely restrained positioning mechanism (IRPM where the external force is provided by the gravitational pull on the platform such as in cable-suspended Stewart platforms. An IRPM-based platform is proposed which uses the external force provided by a compliant member. The compliant central column allows the configuration to achieve n DOFs with n tendons. In particular, this investigation focuses on the angular deflection of the upper platform with respect to the lower platform. The application here is aimed at developing a linkable module that can be connected to one another so as to form a “snake robot” of sorts. Since locomotion takes precedence over positioning in this application, a 3-DOF Stewart platform is adopted. For an arbitrary angular displace of the end-effector, the corresponding length of each tendon can be determined through inverse kinematics. Mathematical singularities are investigated using the traditional analytical method of defining the Jacobian.

  19. Falling films on flexible inclines

    Science.gov (United States)

    Matar, O. K.; Craster, R. V.; Kumar, S.

    2007-11-01

    The nonlinear stability and dynamic behavior of falling fluid films is studied for flow over a flexible substrate. We use asymptotic methods to deduce governing equations valid in various limits. Long-wave theory is used to derive Benney-like coupled equations for the film thickness and substrate deflection. Weakly nonlinear equations are then derived from these equations that, in the limit of large wall damping and/or large wall tension, reduce to the Kuramoto-Sivashinsky equation. These models break down when inertia becomes more significant, so we also use a long-wave approximation in conjunction with integral theory to derive three strongly coupled nonlinear evolution equations for the film thickness, substrate deflection, and film volumetric flow rate valid at higher Reynolds numbers. These equations, accounting for inertia, capillary, viscous, wall tension, and damping effects, are solved over a wide range of parameters. Our results suggest that decreasing wall damping and/or wall tension can promote the development of chaos in the weakly nonlinear regime and lead to severe substrate deformations in the strongly nonlinear regime; these can give rise to situations in which the free surface and underlying substrate come into contact in finite time.

  20. Mundari as a flexible language

    DEFF Research Database (Denmark)

    Hengeveld, Kees; Rijkhoff, Jan

    2005-01-01

    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......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...... by a critical evaluation of the three criteria Evans & Osada (E&O - this volume) use to establish the lack of word class distinctions in a language (section 3). In section 4 we present evidence to support our claim that Mundari has ‘flexible’ basic lexemes (i.e. there is no fundamental distinction between nouns...

  1. 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.

  2. Imparting Icephobicity with Substrate Flexibility

    Science.gov (United States)

    Schutzius, Thomas; Vasileiou, Thomas; Poulikakos, Dimos

    2017-11-01

    Ice accumulation poses serious safety and performance issues for modern infrastructure. Rationally designed superhydrophobic surfaces have demonstrated potential as a passive means to mitigate ice accretion; however, further studies on solutions that reduce impalement and contact time for impacting supercooled droplets are urgently needed. Here we demonstrate the collaborative effect of substrate flexibility and surface texture on enhancing icephobicity and repelling viscous droplets. We first investigate the influence of increased viscosity on impalement resistance and droplet-substrate contact time. Then we examine the effect of droplet partial solidification on recoil by impacting supercooled water droplets onto surfaces containing ice nucleation promoters. We demonstrate a passive method for shedding partially solidified droplets that does not rely on the classic recoil mechanism. Using an energy-based model, we identify a previously unexplored mechanism whereby the substrate oscillation governs the rebound process by efficiently absorbing the droplet kinetic energy and rectifying it back, allowing for droplet recoil. This mechanism applies for a range of droplet viscosities and ice slurries, which do not rebound from rigid superhydrophobic substrates. Partial support of the Swiss National Science Foundation under Grant No. 162565 and the European Research Council under Advanced Grant No. 669908 (INTICE) is acknowledged.

  3. Flexible resources for quantum metrology

    Science.gov (United States)

    Friis, Nicolai; Orsucci, Davide; Skotiniotis, Michalis; Sekatski, Pavel; Dunjko, Vedran; Briegel, Hans J.; Dür, Wolfgang

    2017-06-01

    Quantum metrology offers a quadratic advantage over classical approaches to parameter estimation problems by utilising entanglement and nonclassicality. However, the hurdle of actually implementing the necessary quantum probe states and measurements, which vary drastically for different metrological scenarios, is usually not taken into account. We show that for a wide range of tasks in metrology, 2D cluster states (a particular family of states useful for measurement-based quantum computation) can serve as flexible resources that allow one to efficiently prepare any required state for sensing, and perform appropriate (entangled) measurements using only single qubit operations. Crucially, the overhead in the number of qubits is less than quadratic, thus preserving the quantum scaling advantage. This is ensured by using a compression to a logarithmically sized space that contains all relevant information for sensing. We specifically demonstrate how our method can be used to obtain optimal scaling for phase and frequency estimation in local estimation problems, as well as for the Bayesian equivalents with Gaussian priors of varying widths. Furthermore, we show that in the paradigmatic case of local phase estimation 1D cluster states are sufficient for optimal state preparation and measurement.

  4. Flexible resources for quantum metrology

    International Nuclear Information System (INIS)

    Friis, Nicolai; Orsucci, Davide; Skotiniotis, Michalis; Sekatski, Pavel; Dunjko, Vedran; Briegel, Hans J; Dür, Wolfgang

    2017-01-01

    Quantum metrology offers a quadratic advantage over classical approaches to parameter estimation problems by utilising entanglement and nonclassicality. However, the hurdle of actually implementing the necessary quantum probe states and measurements, which vary drastically for different metrological scenarios, is usually not taken into account. We show that for a wide range of tasks in metrology, 2D cluster states (a particular family of states useful for measurement-based quantum computation) can serve as flexible resources that allow one to efficiently prepare any required state for sensing, and perform appropriate (entangled) measurements using only single qubit operations. Crucially, the overhead in the number of qubits is less than quadratic, thus preserving the quantum scaling advantage. This is ensured by using a compression to a logarithmically sized space that contains all relevant information for sensing. We specifically demonstrate how our method can be used to obtain optimal scaling for phase and frequency estimation in local estimation problems, as well as for the Bayesian equivalents with Gaussian priors of varying widths. Furthermore, we show that in the paradigmatic case of local phase estimation 1D cluster states are sufficient for optimal state preparation and measurement. (paper)

  5. Rigidification of the autolysis loop enhances Na(+) binding to thrombin.

    Science.gov (United States)

    Pozzi, Nicola; Chen, Raymond; Chen, Zhiwei; Bah, Alaji; Di Cera, Enrico

    2011-11-01

    Binding of Na(+) to thrombin ensures high activity toward physiological substrates and optimizes the procoagulant and prothrombotic roles of the enzyme in vivo. Under physiological conditions of pH and temperature, the binding affinity of Na(+) is weak due to large heat capacity and enthalpy changes associated with binding, and the K(d)=80 mM ensures only 64% saturation of the site at the concentration of Na(+) in the blood (140 mM). Residues controlling Na(+) binding and activation have been identified. Yet, attempts to improve the interaction of Na(+) with thrombin and possibly increase catalytic activity under physiological conditions have so far been unsuccessful. Here we report how replacement of the flexible autolysis loop of human thrombin with the homologous rigid domain of the murine enzyme results in a drastic (up to 10-fold) increase in Na(+) affinity and a significant improvement in the catalytic activity of the enzyme. Rigidification of the autolysis loop abolishes the heat capacity change associated with Na(+) binding observed in the wild-type and also increases the stability of thrombin. These findings have general relevance to protein engineering studies of clotting proteases and trypsin-like enzymes. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. Rigidification of the autolysis loop enhances Na+ binding to thrombin

    Science.gov (United States)

    Pozzi, Nicola; Chen, Raymond; Chen, Zhiwei; Bah, Alaji; Di Cera, Enrico

    2011-01-01

    Binding of Na+ to thrombin ensures high activity toward physiological substrates and optimizes the procoagulant and prothrombotic roles of the enzyme in vivo. Under physiological conditions of pH and temperature, the binding affinity of Na+ is weak due to large heat capacity and enthalpy changes associated with binding, and the Kd=80 mM ensures only 64% saturation of the site at the concentration of Na+ in the blood (140 mM). Residues controlling Na+ binding and activation have been identified. Yet, attempts to improve the interaction of Na+ with thrombin and possibly increase catalytic activity under physiological conditions have so far been unsuccessful. Here we report how replacement of the flexible autolysis loop of human thrombin with the homologous rigid domain of the murine enzyme results in a drastic (up to 10-fold) increase in Na+ affinity and a significant improvement in the catalytic activity of the enzyme. Rigidification of the autolysis loop abolishes the heat capacity change associated with Na+ binding observed in the wild-type and also increases the stability of thrombin. These findings have general relevance to protein engineering studies of clotting proteases and trypsin-like enzymes. PMID:21536369

  7. IEA EBC Annex 67 Energy Flexible Buildings

    DEFF Research Database (Denmark)

    Marszal, Anna Joanna; Jensen, Søren Østergaard

    2016-01-01

    know ledge on and demonstration of the Energy Flexibility Buildings can provide for the energy grids as well of to identify critical aspects and possible solutions to manage this Energy Flexibility. The paper discusses the background, the aims and the work plan of IEA (International Energy Agency) EBC......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......, allowing for a larger roll out of renewable technologies. The Energy Flexibility of a building is the ability to manage its energy demand and generation according to local climate conditions, user needs and grid requirements. Energy Flexibility of buildings will thus allow for demand side management...

  8. Free energy landscape of siRNA-polycation complexation: Elucidating the effect of molecular geometry, polymer flexibility, and charge neutralization.

    Directory of Open Access Journals (Sweden)

    Gianvito Grasso

    Full Text Available The success of medical threatments with DNA and silencing interference RNA is strongly related to the design of efficient delivery technologies. Cationic polymers represent an attractive strategy to serve as nucleic-acid carriers with the envisioned advantages of efficient complexation, low cost, ease of production, well-defined size, and low polydispersity index. However, the balance between efficacy and toxicity (safety of these polymers is a challenge and in need of improvement. With the aim of designing more effective polycationic-based gene carriers, many parameters such as carrier morphology, size, molecular weight, surface chemistry, and flexibility/rigidity ratio need to be taken into consideration. In the present work, the binding mechanism of three cationic polymers (polyarginine, polylysine and polyethyleneimine to a model siRNA target is computationally investigated at the atomistic level. In order to better understand the polycationic carrier-siRNA interactions, replica exchange molecular dynamic simulations were carried out to provide an exhaustive exploration of all the possible binding sites, taking fully into account the siRNA flexibility together with the presence of explicit solvent and ions. Moreover, well-tempered metadynamics simulations were employed to elucidate how molecular geometry, polycation flexibility, and charge neutralization affect the siRNA-polycations free energy landscape in term of low-energy binding modes and unbinding free energy barriers. Significant differences among polymer binding modes have been detected, revealing the advantageous binding properties of polyarginine and polylysine compared to polyethyleneimine.

  9. 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

    2016-07-18

    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.

  10. OSPREY: protein design with ensembles, flexibility, and provable algorithms.

    Science.gov (United States)

    Gainza, Pablo; Roberts, Kyle E; Georgiev, Ivelin; Lilien, Ryan H; Keedy, Daniel A; Chen, Cheng-Yu; Reza, Faisal; Anderson, Amy C; Richardson, David C; Richardson, Jane S; Donald, Bruce R

    2013-01-01

    We have developed a suite of protein redesign algorithms that improves realistic in silico modeling of proteins. These algorithms are based on three characteristics that make them unique: (1) improved flexibility of the protein backbone, protein side-chains, and ligand to accurately capture the conformational changes that are induced by mutations to the protein sequence; (2) modeling of proteins and ligands as ensembles of low-energy structures to better approximate binding affinity; and (3) a globally optimal protein design search, guaranteeing that the computational predictions are optimal with respect to the input model. Here, we illustrate the importance of these three characteristics. We then describe OSPREY, a protein redesign suite that implements our protein design algorithms. OSPREY has been used prospectively, with experimental validation, in several biomedically relevant settings. We show in detail how OSPREY has been used to predict resistance mutations and explain why improved flexibility, ensembles, and provability are essential for this application. OSPREY is free and open source under a Lesser GPL license. The latest version is OSPREY 2.0. The program, user manual, and source code are available at www.cs.duke.edu/donaldlab/software.php. osprey@cs.duke.edu. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. 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

  12. Functional Advantages of Conserved Intrinsic Disorder in RNA-Binding Proteins.

    Science.gov (United States)

    Varadi, Mihaly; Zsolyomi, Fruzsina; Guharoy, Mainak; Tompa, Peter

    2015-01-01

    Proteins form large macromolecular assemblies with RNA that govern essential molecular processes. RNA-binding proteins have often been associated with conformational flexibility, yet the extent and functional implications of their intrinsic disorder have never been fully assessed. Here, through large-scale analysis of comprehensive protein sequence and structure datasets we demonstrate the prevalence of intrinsic structural disorder in RNA-binding proteins and domains. We addressed their functionality through a quantitative description of the evolutionary conservation of disordered segments involved in binding, and investigated the structural implications of flexibility in terms of conformational stability and interface formation. We conclude that the functional role of intrinsically disordered protein segments in RNA-binding is two-fold: first, these regions establish extended, conserved electrostatic interfaces with RNAs via induced fit. Second, conformational flexibility enables them to target different RNA partners, providing multi-functionality, while also ensuring specificity. These findings emphasize the functional importance of intrinsically disordered regions in RNA-binding proteins.

  13. Functional Advantages of Conserved Intrinsic Disorder in RNA-Binding Proteins.

    Directory of Open Access Journals (Sweden)

    Mihaly Varadi

    Full Text Available Proteins form large macromolecular assemblies with RNA that govern essential molecular processes. RNA-binding proteins have often been associated with conformational flexibility, yet the extent and functional implications of their intrinsic disorder have never been fully assessed. Here, through large-scale analysis of comprehensive protein sequence and structure datasets we demonstrate the prevalence of intrinsic structural disorder in RNA-binding proteins and domains. We addressed their functionality through a quantitative description of the evolutionary conservation of disordered segments involved in binding, and investigated the structural implications of flexibility in terms of conformational stability and interface formation. We conclude that the functional role of intrinsically disordered protein segments in RNA-binding is two-fold: first, these regions establish extended, conserved electrostatic interfaces with RNAs via induced fit. Second, conformational flexibility enables them to target different RNA partners, providing multi-functionality, while also ensuring specificity. These findings emphasize the functional importance of intrinsically disordered regions in RNA-binding proteins.

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

    Science.gov (United States)

    Cobley, Matthew J; Rayfield, Emily J; Barrett, Paul M

    2013-01-01

    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. 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.

  16. 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.

  17. 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 Günther; Thomsen, J.K.; Graversen, J. H.

    2004-01-01

    . A conserved proline, which was found to be in the cis conformation in holoTN3, is in apoTN3 predominantly in the trans conformation. Backbone dynamics indicate that, in apoTN3 especially, two of the three calcium-binding loops and two of the three K4-binding residues exhibit increased flexibility, whereas...

  18. 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.

  19. 49 CFR 178.940 - Standards for flexible Large Packagings.

    Science.gov (United States)

    2010-10-01

    .... Flexible Large Packagings types are designated: (1) 51H flexible plastics. (2) 51M flexible paper. (b... this subchapter, flexible Large Packaging must be resistant to aging and degradation caused by ultraviolet radiation. (5) For plastic flexible Large Packagings, if necessary, protection against ultraviolet...

  20. Graphene-cellulose paper flexible supercapacitors

    Energy Technology Data Exchange (ETDEWEB)

    Weng, Zhe; Su, Yang; Li, Feng; Du, Jinhong; Cheng, Hui-Ming [Shenyang National Laboratory for Materials Science, Institute of Metal Research, Chinese Academy of Sciences, 72 Wenhua Road, Shenyang 110016 (China); Wang, Da-Wei [ARC Centre of Excellence for Functional Nanomaterials, Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St Lucia, Brisbane, Qld 4072 (Australia)

    2011-10-15

    A simple and scalable method to fabricate graphene-cellulose paper (GCP) membranes is reported; these membranes exhibit great advantages as freestanding and binder-free electrodes for flexible supercapacitors. The GCP electrode consists of a unique three-dimensional interwoven structure of graphene nanosheets and cellulose fibers and has excellent mechanical flexibility, good specific capacitance and power performance, and excellent cyclic stability. The electrical conductivity of the GCP membrane shows high stability with a decrease of only 6% after being bent 1000 times. This flexible GCP electrode has a high capacitance per geometric area of 81 mF cm{sup -2}, which is equivalent to a gravimetric capacitance of 120 F g{sup -1} of graphene, and retains >99% capacitance over 5000 cycles. Several types of flexible GCP-based polymer supercapacitors with various architectures are assembled to meet the power-energy requirements of typical flexible or printable electronics. Under highly flexible conditions, the supercapacitors show a high capacitance per geometric area of 46 mF cm{sup -2} for the complete devices. All the results demonstrate that polymer supercapacitors made using GCP membranes are versatile and may be used for flexible and portable micropower devices. (Copyright copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  1. ESF [Exploratory Shaft Facility] flexibility analysis

    International Nuclear Information System (INIS)

    Brusenback, R.W.

    1987-03-01

    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

  2. Factors impeding flexible inpatient unit design.

    Science.gov (United States)

    Pati, Debajyoti; Evans, Jennie; Harvey, Thomas E; Bazuin, Doug

    2012-01-01

    To identify and examine factors extraneous to the design decision-making process that could impede the optimization of flexibility on inpatient units. A 2006 empirical study to identify domains of design decisions that affect flexibility on inpatient units found some indication in the context of the acuity-adaptable operational model that factors extraneous to the design process could have negatively influenced the successful implementation of the model. This raised questions regarding extraneous factors that might influence the successful optimization of flexibility. An exploratory, qualitative method was adopted to examine the question. Stakeholders from five recently built acute care inpatient units participated in the study, which involved three types of data collection: (1) verbal protocol data from a gaming session; (2) in-depth semi-structured interviews; and (3) shadowing frontline personnel. Data collection was conducted between June 2009 and November 2010. The study revealed at least nine factors extraneous to the design process that have the potential to hinder the optimization of flexibility in four domains: (1) systemic; (2) cultural; (3) human; and (4) financial. Flexibility is critical to hospital operations in the new healthcare climate, where cost reduction constitutes a vital target. From this perspective, flexibility and efficiency strategies can be influenced by (1) return on investment, (2) communication, (3) culture change, and (4) problem definition. Extraneous factors identified in this study could also affect flexibility in other care settings; therefore, these findings may be viewed from the overall context of hospital design.

  3. The role of side chain conformational flexibility in surface recognition by Tenebrio molitor antifreeze protein

    Science.gov (United States)

    Daley, Margaret E.; Sykes, Brian D.

    2003-01-01

    Two-dimensional nuclear magnetic resonance spectroscopy was used to investigate the flexibility of the threonine side chains in the β-helical Tenebrio molitor antifreeze protein (TmAFP) at low temperatures. From measurement of the 3Jαβ 1H-1H scalar coupling constants, the χ1 angles and preferred rotamer populations can be calculated. It was determined that the threonines on the ice-binding face of the protein adopt a preferred rotameric conformation at near freezing temperatures, whereas the threonines not on the ice-binding face sample many rotameric states. This suggests that TmAFP maintains a preformed ice-binding conformation in solution, wherein the rigid array of threonines that form the AFP-ice interface matches the ice crystal lattice. A key factor in binding to the ice surface and inhibition of ice crystal growth appears to be the close surface-to-surface complementarity between the AFP and crystalline ice, and the lack of an entropic penalty associated with freezing out motions in a flexible ligand. PMID:12824479

  4. Flexible removable partial dentures: a basic overview.

    Science.gov (United States)

    Hill, Edward E; Rubel, Barry; Smith, John B

    2014-01-01

    For many years, flexible resin materials have been available for fabricating removable partial denture (RPD) prostheses. Using a nonrigid material for the major connector or other components of an RPD may be a consideration for certain patients. Except for the promotional literature that has been written for flexible resin dentures, there is very little information available in the dental literature concerning nonrigid RPDs. As a result, the decision to use this treatment option depends on the judgment and experience of the dentist and fabricating laboratory. This article summarizes clinically pertinent information about flexible, nonrigid partial dentures.

  5. Optimal reduction of flexible dynamic system

    International Nuclear Information System (INIS)

    Jankovic, J.

    1994-01-01

    Dynamic system reduction is basic procedure in various problems of active control synthesis of flexible structures. In this paper is presented direct method for system reduction by explicit extraction of modes included in reduced model form. Criterion for optimal system discrete approximation in synthesis reduced dynamic model is also presented. Subjected method of system decomposition is discussed in relation to the Schur method of solving matrix algebraic Riccati equation as condition for system reduction. By using exposed method procedure of flexible system reduction in addition with corresponding example is presented. Shown procedure is powerful in problems of active control synthesis of flexible system vibrations

  6. Evaluation of the flexibility of protective gloves.

    Science.gov (United States)

    Harrabi, Lotfi; Dolez, Patricia I; Vu-Khanh, Toan; Lara, Jaime

    2008-01-01

    Two mechanical methods have been developed for the characterization of the flexibility of protective gloves, a key factor affecting their degree of usefulness for workers. The principle of the first method is similar to the ASTM D 4032 standard relative to fabric stiffness and simulates the deformations encountered by gloves that are not tight fitted to the hand. The second method characterizes the flexibility of gloves that are worn tight fitted. Its validity was theoretically verified for elastomer materials. Both methods should prove themselves as valuable tools for protective glove manufacturers, allowing for the characterization of their existing products in terms of flexibility and the development of new ones better fitting workers' needs.

  7. Flexibility: the grid knows how to cope

    International Nuclear Information System (INIS)

    Boulanger, Vincent

    2017-01-01

    As variable energy sources, such as wind power and photovoltaic solar power, are more and more penetrating into the electric power mix, flexibility is therefore a growing challenge, notably concerning the power demand variability. As a matter of fact, experts show that, contrary to the popular belief, there is no needs to use thermal power plants, power-to-gas systems or energy storage for that, thanks to innovative power flexibility and load management tools and technologies (nuclear power plants are also gaining the aptitude to be more flexible than before). The frequency issue is addressed

  8. 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...

  9. The conformational stability and flexibility of insulin with an additional intramolecular cross-link

    International Nuclear Information System (INIS)

    Brems, D.N.; Brown, P.L.; Nakagawa, S.H.; Tager, H.S.

    1991-01-01

    The conformational stability and flexibility of insulin containing a cross-link between the alpha-amino group of the A-chain to the epsilon-amino group of Lys29 of the B-chain was examined. The cross-link varied in length from 2 to 12 carbon atoms. The conformational stability was determined by guanidine hydrochloride-induced equilibrium denaturation and flexibility was assessed by H2O/D2O amide exchange. The cross-link has substantial effects on both conformational stability and flexibility which depend on its length. In general, the addition of a cross-link enhances conformational stability and decreases flexibility. The optimal length for enhanced stability and decreased flexibility was the 6-carbon link. For the 6-carbon link the Gibbs free energy of unfolding was 8.0 kcal/mol compared to 4.5 kcal/mol for insulin, and the amide exchange rate decreased by at least 3-fold. A very short cross-link (i.e. the 2-carbon link) caused conformational strain that was detectable by a lack of stabilization in the Gibbs free energy of unfolding and enhancement in the amide exchange rate compared to insulin. The effect of the cross-link length on insulin hydrodynamic properties is discussed relative to previously obtained receptor binding results

  10. 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.

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

    International Nuclear Information System (INIS)

    Zhou, Changjian; Shu, Yi; Yang, Yi; Ren, Tian-Ling; Jin, Hao; Dong, Shu-Rong; Chan, Mansun

    2015-01-01

    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)

  12. OLIFE: Tight Binding Code for Transmission Coefficient Calculation

    Science.gov (United States)

    Mijbil, Zainelabideen Yousif

    2018-05-01

    A new and human friendly transport calculation code has been developed. It requires a simple tight binding Hamiltonian as the only input file and uses a convenient graphical user interface to control calculations. The effect of magnetic field on junction has also been included. Furthermore the transmission coefficient can be calculated between any two points on the scatterer which ensures high flexibility to check the system. Therefore Olife can highly be recommended as an essential tool for pretesting studying and teaching electron transport in molecular devices that saves a lot of time and effort.

  13. Free-form Flexible Lithium-Ion Microbattery

    KAUST Repository

    Kutbee, Arwa T.; Ghoneim, Mohamed T.; Ahmed, Sally; Hussain, Muhammad Mustafa

    2016-01-01

    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

  14. Flexible lithium-ion planer thin-film battery

    KAUST Repository

    Kutbee, Arwa T.; Ghoneim, Mohamed T.; Hussain, Muhammad Mustafa

    2016-01-01

    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

  15. Pictorial binding: endeavor to classify

    Directory of Open Access Journals (Sweden)

    Zinchenko S.

    2015-01-01

    Full Text Available The article is devoted to the classification of bindings of the 1-19th centuries with a unique and untypical book binding decoration technique (encaustic, tempera and oil paintings. Analysis of design features, materials and techniques of art decoration made it possible to identify them as a separate type - pictorial bindings and divide them into four groups. The first group consists of Coptic bindings, decorated with icon-painting images in encaustic technique. The second group is made up of leather Western bindings of the 13-14th centuries, which have the decoration and technique of ornamentation close to iconography. The third group involves parchment bindings, ornamentation technique of which is closer to the miniature. The last group comprises bindings of East Slavic origin of the 15-19th centuries, decorated with icon-painting pictures made in the technique of tempera or oil painting. The proposed classification requires further basic research as several specific kinds of bindings have not yet been investigated

  16. Flexible public transportation services in Florida.

    Science.gov (United States)

    2013-08-01

    This synthesis research provides an overview of the current use of flexible transportation services in Florida through administration of a survey and subsequent identification and examination of case study locations. The research included a literatur...

  17. Thin Flexible IMM Solar Array, Phase II

    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....

  18. Cognitive flexibility in drawings of bilingual children.

    Science.gov (United States)

    Adi-Japha, Esther; Berberich-Artzi, Jennie; Libnawi, Afaf

    2010-01-01

    A. Karmiloff-Smith's (1990) task of drawing a nonexistent object is considered to be a measure of cognitive flexibility. The notion of earlier emergence of cognitive flexibility in bilingual children motivated the current researchers to request 4- and 5-year-old English-Hebrew and Arabic-Hebrew bilingual children and their monolingual peers to draw a flower and a house that do not exist (N=80). Bilinguals exhibited a significantly higher rate of interrepresentational flexibility in their drawings (e.g., "a giraffe flower,"a chair-house," found in 28 of 54 drawings), whereas the level of complex intrarepresentational change was similar across groups. Interrepresentational drawings were previously reported only for children older than 7 years. The specific mechanisms by which bilinguals' language experience may lead to interrepresentational flexibility are discussed. © 2010 The Authors. Child Development © 2010 Society for Research in Child Development, Inc.

  19. Two dimensional nanomaterials for flexible supercapacitors.

    Science.gov (United States)

    Peng, Xu; Peng, Lele; Wu, Changzheng; Xie, Yi

    2014-05-21

    Flexible supercapacitors, as one of most promising emerging energy storage devices, are of great interest owing to their high power density with great mechanical compliance, making them very suitable as power back-ups for future stretchable electronics. Two-dimensional (2D) nanomaterials, including the quasi-2D graphene and inorganic graphene-like materials (IGMs), have been greatly explored to providing huge potential for the development of flexible supercapacitors with higher electrochemical performance. This review article is devoted to recent progresses in engineering 2D nanomaterials for flexible supercapacitors, which survey the evolution of electrode materials, recent developments in 2D nanomaterials and their hybrid nanostructures with regulated electrical properties, and the new planar configurations of flexible supercapacitors. Furthermore, a brief discussion on future directions, challenges and opportunities in this fascinating area is also provided.

  20. Resonant Electromagnetic Shunt Damping of Flexible Structures

    DEFF Research Database (Denmark)

    Høgsberg, Jan Becker

    2016-01-01

    Electromagnetic transducers convert mechanical energy to electrical energy and vice versa. Effective passive vibration damping of flexible structures can therefore be introduced by shunting with an accurately calibrated resonant electrical network thatcontains a capacitor to create the desired...

  1. 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.

  2. Flexibility-enabling Contracts in Electricity Markets

    DEFF Research Database (Denmark)

    Boscan, Luis; Poudineh, Rahmatallah

    As the share of intermittent renewable energy increases in the generation mix, power systems are exposed to greater levels of uncertainty and risk, which requires planners, policy and business decision makers to incentivise flexibility, that is: their adaptability to unforeseen variations....... Additionally, along with traditional sources, which already enable flexibility, a number of business models, such as thermostat-based demand response, aggregators and small storage providers, are emerging in electricity markets and expected to constitute important sources of flexibility in future decentralised...... power systems. However, due to presence of high transaction costs, relative to the size of resource, the emerging small resources cannot directly participate in an organised electricity market and/or compete. This paper asks the fundamental question of how should the provision of flexibility, as a multi...

  3. Alternative methods of flexible base compaction acceptance.

    Science.gov (United States)

    2012-11-01

    "This report presents the results from the second year of research work investigating issues with flexible base acceptance testing within the Texas Department of Transportation. This second year of work focused on shadow testing non-density-based acc...

  4. Thin Flexible IMM Solar Array, Phase I

    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...

  5. 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)

  6. 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.

  7. Mixture design procedure for flexible base.

    Science.gov (United States)

    2013-04-01

    This document provides information on mixture design requirements for a flexible base course. Sections : design requirements, job mix formula, contractor's responsibility, and engineer's responsibility. Tables : material requirements; requirements fo...

  8. Receptiveness to Flexible Employment at Hungarian SMEs

    Directory of Open Access Journals (Sweden)

    Ákos Essősy

    2018-04-01

    Full Text Available Nowadays, only companies that are adaptable and flexible in their structure and processes can survive. The basis for a motivated company aiming for peak performance is organisational innovation. Hungary is one of the less innovative countries in Europe. Only organisations that can integrate new solutions smoothly into their everyday operations will remain truly competitive. The Government of Hungary, in its Partnership Agreement with the European Union, set out the goals for improving and supporting the adaptability of enterprises, the promotion of flexible and family-friendly workplace practices and services, and the employment of women with young children. The aim of this study is to demonstrate, through a Hungarian example, the receptiveness of Hungarian small and medium-sized enterprises to flexible forms of employment. The effect of flexible employment on economic adaptability and competitiveness through workforce efficiency and retention is examined. Its aim is the raise the awareness of options to increase employment among Hungarian SME managers.

  9. Flexible receiver adapter formal design review

    International Nuclear Information System (INIS)

    Krieg, S.A.

    1995-01-01

    This memo summarizes the results of the Formal (90%) Design Review process and meetings held to evaluate the design of the Flexible Receiver Adapters, support platforms, and associated equipment. The equipment is part of the Flexible Receiver System used to remove, transport, and store long length contaminated equipment and components from both the double and single-shell underground storage tanks at the 200 area tank farms

  10. Flexible and Cellulose-based Organic Electronics

    OpenAIRE

    Edberg, Jesper

    2017-01-01

    Organic electronics is the study of organic materials with electronic functionality and the applications of such materials. In the 1970s, the discovery that polymers can be made electrically conductive led to an explosion within this field which has continued to grow year by year. One of the attractive features of organic electronic materials is their inherent mechanical flexibility, which has led to the development of numerous flexible electronics technologies such as organic light emitting ...

  11. Flexible Dermal Armor : Designs Learned from Nature

    OpenAIRE

    Chen, Irene Hsu

    2015-01-01

    Designs derived from nature have become a perfect blueprint for today's engineers and scientists to follow and implement. One particularly noted area is the defense industry, wherein flexible dermal armor inspired by nature has been pioneering many sophisticated technologies and designs in recent years. Designers today are considering borrowing aspects of flexibility and mobility of natural dermal armors to enhance the maneuverability of man-made armor by imitating the following mechanisms : ...

  12. RT-18: Value of Flexibility. Phase 1

    Science.gov (United States)

    2010-09-25

    following examples of putative flexibility:  ― Nike shoes provide flexibility to the customer in terms of color choice, customized emblems (such...investment opportunity, he constructs a synthetic portfolio of a brand -new factory in a developing country, such as China, and bonds. Maybe the...kit using a combination of Inertial Navigation (INS) and the satellite based Global Positioning System (GPS). These Joint Direct Attack Munition

  13. [Flexible ENT endoscopy--video technic].

    Science.gov (United States)

    Rasinger, G A; Horak, F

    1985-02-01

    This study discusses the solutions to the problem of documenting moving processes in the field of otolaryngology. A flexible bronchoscope and video equipment connected to it are presented as a specific solution of the problem, with ample of observations. A technical comparison is used as the basis for a discussion of the pros and cons of the video and film techniques. A successful arrangement of examination facilities illustrates the future of flexible-endoscope techniques in the field of otolaryngology.

  14. 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....

  15. Flexible benefits plans. Perceptions of their effectiveness.

    Science.gov (United States)

    Agho, A O

    1995-01-01

    Flexible benefits plans have been used in businesses since the 1970s to control healthcare costs and meet the needs of an increasingly diverse work force. More recently, healthcare organizations have begun to implement the flexible benefits concept. This study collected data from human resources executives at hospitals with and without flex plans to investigate how they perceive the effectiveness of and the problems associated with such plans.

  16. 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...

  17. Functional flexibility in wild bonobo vocal behaviour

    Directory of Open Access Journals (Sweden)

    Zanna Clay

    2015-08-01

    Full Text Available A shared principle in the evolution of language and the development of speech is the emergence of functional flexibility, the capacity of vocal signals to express a range of emotional states independently of context and biological function. Functional flexibility has recently been demonstrated in the vocalisations of pre-linguistic human infants, which has been contrasted to the functionally fixed vocal behaviour of non-human primates. Here, we revisited the presumed chasm in functional flexibility between human and non-human primate vocal behaviour, with a study on our closest living primate relatives, the bonobo (Pan paniscus. We found that wild bonobos use a specific call type (the “peep” across a range of contexts that cover the full valence range (positive-neutral-negative in much of their daily activities, including feeding, travel, rest, aggression, alarm, nesting and grooming. Peeps were produced in functionally flexible ways in some contexts, but not others. Crucially, calls did not vary acoustically between neutral and positive contexts, suggesting that recipients take pragmatic information into account to make inferences about call meaning. In comparison, peeps during negative contexts were acoustically distinct. Our data suggest that the capacity for functional flexibility has evolutionary roots that predate the evolution of human speech. We interpret this evidence as an example of an evolutionary early transition away from fixed vocal signalling towards functional flexibility.

  18. 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.

  19. Flexibility evaluation of multiechelon supply chains.

    Directory of Open Access Journals (Sweden)

    João Flávio de Freitas Almeida

    Full Text Available Multiechelon supply chains are complex logistics systems that require flexibility and coordination at a tactical level to cope with environmental uncertainties in an efficient and effective manner. To cope with these challenges, mathematical programming models are developed to evaluate supply chain flexibility. However, under uncertainty, supply chain models become complex and the scope of flexibility analysis is generally reduced. This paper presents a unified approach that can evaluate the flexibility of a four-echelon supply chain via a robust stochastic programming model. The model simultaneously considers the plans of multiple business divisions such as marketing, logistics, manufacturing, and procurement, whose goals are often conflicting. A numerical example with deterministic parameters is presented to introduce the analysis, and then, the model stochastic parameters are considered to evaluate flexibility. The results of the analysis on supply, manufacturing, and distribution flexibility are presented. Tradeoff analysis of demand variability and service levels is also carried out. The proposed approach facilitates the adoption of different management styles, thus improving supply chain resilience. The model can be extended to contexts pertaining to supply chain disruptions; for example, the model can be used to explore operation strategies when subtle events disrupt supply, manufacturing, or distribution.

  20. The value of flexibility in power markets

    International Nuclear Information System (INIS)

    Goutte, Stephane; Vassilopoulos, Philippe

    2017-01-01

    In this paper we attempt to quantify the net revenues that can be captured by a flexible resource able to react to the short term price variations on the day-ahead and intra-day markets in Germany. We find that the difference between day-ahead and intra-day revenues for a flexible resource has been increasing (although the profitability has been decreasing on both markets). This difference is more pronounced once 15 mn price variations can be captured by a flexible resource. The net revenues from the local 15 mn auction (which is held 3 hours after the hourly 'coupled' day-ahead auction) are more than eight times higher than the day-ahead hourly auction but below the net revenues that can be captured with the high prices from the continuous market. The results of the backward-looking empirical estimations allow us to distinguish and quantify two components of flexibility: (1) the 'immediacy' value as we are approaching real-time and the urgency of the delivery increases (this value is revealed during the continuous intra-day process and is highly linked to the stochastic nature of power supply and demand (i.e. wind/solar forecasts, forced outages of thermal generation,...) forecast error risk), and (2) the 'flexibility' component as a resource can react to variations of shorter granularity (15 mn Vs 60 mn). We model and quantify the 'flexibility' component. (authors)

  1. Flexibility evaluation of multiechelon supply chains.

    Science.gov (United States)

    Almeida, João Flávio de Freitas; Conceição, Samuel Vieira; Pinto, Luiz Ricardo; de Camargo, Ricardo Saraiva; Júnior, Gilberto de Miranda

    2018-01-01

    Multiechelon supply chains are complex logistics systems that require flexibility and coordination at a tactical level to cope with environmental uncertainties in an efficient and effective manner. To cope with these challenges, mathematical programming models are developed to evaluate supply chain flexibility. However, under uncertainty, supply chain models become complex and the scope of flexibility analysis is generally reduced. This paper presents a unified approach that can evaluate the flexibility of a four-echelon supply chain via a robust stochastic programming model. The model simultaneously considers the plans of multiple business divisions such as marketing, logistics, manufacturing, and procurement, whose goals are often conflicting. A numerical example with deterministic parameters is presented to introduce the analysis, and then, the model stochastic parameters are considered to evaluate flexibility. The results of the analysis on supply, manufacturing, and distribution flexibility are presented. Tradeoff analysis of demand variability and service levels is also carried out. The proposed approach facilitates the adoption of different management styles, thus improving supply chain resilience. The model can be extended to contexts pertaining to supply chain disruptions; for example, the model can be used to explore operation strategies when subtle events disrupt supply, manufacturing, or distribution.

  2. Flexible and rigid cystoscopy in women.

    Science.gov (United States)

    Gee, Jason R; Waterman, Bradley J; Jarrard, David F; Hedican, Sean P; Bruskewitz, Reginald C; Nakada, Stephen Y

    2009-01-01

    Previous studies have evaluated the tolerability of rigid versus flexible cystoscopy in men. Similar studies, however, have not been performed in women. We sought to determine whether office-based flexible cystoscopy was better tolerated than rigid cystoscopy in women. Following full IRB approval, women were prospectively randomized in a single-blind manner. Patients were randomized to flexible or rigid cystoscopy and draped in the lithotomy position to maintain blinding of the study. Questionnaires evaluated discomfort before, during, and after cystoscopy. Thirty-six women were randomized to flexible (18) or rigid (18) cystoscopy. Indications were surveillance (16), hematuria (15), recurrent UTIs (2), voiding dysfunction (1), and other (2). All questionnaires were returned by 31/36 women. Using a 10-point visual analog scale (VAS), median discomfort during the procedure for flexible and rigid cystoscopy were 1.4 and 1.8, respectively, in patients perceiving pain. Median recalled pain 1 week later was similar at 0.8 and 1.15, respectively. None of these differences were statistically significant. Flexible and rigid cystoscopy are well tolerated in women. Discomfort during and after the procedure is minimal in both groups. Urologists should perform either procedure in women based on their preference and skill level.

  3. Flexible magnetic thin films and devices

    Science.gov (United States)

    Sheng, Ping; Wang, Baomin; Li, Runwei

    2018-01-01

    Flexible electronic devices are highly attractive for a variety of applications such as flexible circuit boards, solar cells, paper-like displays, and sensitive skin, due to their stretchable, biocompatible, light-weight, portable, and low cost properties. Due to magnetic devices being important parts of electronic devices, it is essential to study the magnetic properties of magnetic thin films and devices fabricated on flexible substrates. In this review, we mainly introduce the recent progress in flexible magnetic thin films and devices, including the study on the stress-dependent magnetic properties of magnetic thin films and devices, and controlling the properties of flexible magnetic films by stress-related multi-fields, and the design and fabrication of flexible magnetic devices. Project supported by the National Key R&D Program of China (No. 2016YFA0201102), the National Natural Science Foundation of China (Nos. 51571208, 51301191, 51525103, 11274321, 11474295, 51401230), the Youth Innovation Promotion Association of the Chinese Academy of Sciences (No. 2016270), the Key Research Program of the Chinese Academy of Sciences (No. KJZD-EW-M05), the Ningbo Major Project for Science and Technology (No. 2014B11011), the Ningbo Science and Technology Innovation Team (No. 2015B11001), and the Ningbo Natural Science Foundation (No. 2015A610110).

  4. 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 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...

  5. Molecular switches for pheromone release from a moth pheromone-binding protein

    International Nuclear Information System (INIS)

    Xu Wei; Leal, Walter S.

    2008-01-01

    Pheromone-binding proteins (PBPs) are involved in the uptake of pheromones from pores on the antennae, transport through an aqueous environment surrounding the olfactory receptor neurons, and fast delivery to pheromone receptors. We tested the hypothesis that a C-terminal segment and a flexible loop are involved in the release of pheromones to membrane-bound receptors. We expressed in Escherichia coli 11 mutants of the PBP from the silkworm moth, BmorPBP, taking into consideration structural differences between the forms with high and low binding affinity. The N-terminus was truncated and His-69, His-70 and His-95 at the base of a flexible loop, and a cluster of acidic residues at the C-terminus were mutated. Binding assays and circular dichroism analyses support a mechanism involving protonation of acidic residues Asp-132 and Glu-141 at the C-terminus and histidines, His-70 and His-95, in the base of a loop covering the binding pocket. The former leads to the formation of a new α-helix, which competes with pheromone for the binding pocket, whereas positive charge repulsion of the histidines opens the opposite side of the binding pocket

  6. Protein Localization with Flexible DNA or RNA

    DEFF Research Database (Denmark)

    Bernhardsson, Per Johan Sebastian; Mitarai, Namiko; Sneppen, Kim

    2012-01-01

    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...

  7. 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.

  8. Work Life Balance in the Netherlands: Flexible working hours and a flexible working place (Japanese)

    OpenAIRE

    KENJOH Eiko

    2011-01-01

    The purpose of this paper is to investigate the nature of Dutch approach to achieving Work Life Balance (WLB) and to draw policy implications for Japan. It is argued that flexibility of working hours and flexibility offered at one's working place are essential elements of WLB. In this respect, the Netherlands has attained relatively advanced policies and practices. For instance, workers in the Netherlands enjoy a strong degree of flexibility in terms of working hours, a system that strives to...

  9. Inter-Vertebral Flexibility of the Ostrich Neck: Implications for Estimating Sauropod Neck Flexibility

    OpenAIRE

    Cobley, Matthew J.; Rayfield, Emily J.; Barrett, Paul M.

    2013-01-01

    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 o...

  10. The Flexibility of Organization and the flexibility of product – premises of organizational success

    OpenAIRE

    Todorut, Amalia Venera

    2008-01-01

    Flexibility represents the ability of a manufactural system to adapt to some diversified tasks of production, thus to assure an economic efficiency – the rapport time/cost should be optimum, with insignificant structure changes within a long period of time. The central role of flexibility is to permit the survival and the success of the organizations in a turbulent circumstance, which is characteristic to the new world tendencies. The more flexible the organization becomes, the better it resp...

  11. Sampling protein motion and solvent effect during ligand binding

    Science.gov (United States)

    Limongelli, Vittorio; Marinelli, Luciana; Cosconati, Sandro; La Motta, Concettina; Sartini, Stefania; Mugnaini, Laura; Da Settimo, Federico; Novellino, Ettore; Parrinello, Michele

    2012-01-01

    An exhaustive description of the molecular recognition mechanism between a ligand and its biological target is of great value because it provides the opportunity for an exogenous control of the related process. Very often this aim can be pursued using high resolution structures of the complex in combination with inexpensive computational protocols such as docking algorithms. Unfortunately, in many other cases a number of factors, like protein flexibility or solvent effects, increase the degree of complexity of ligand/protein interaction and these standard techniques are no longer sufficient to describe the binding event. We have experienced and tested these limits in the present study in which we have developed and revealed the mechanism of binding of a new series of potent inhibitors of Adenosine Deaminase. We have first performed a large number of docking calculations, which unfortunately failed to yield reliable results due to the dynamical character of the enzyme and the complex role of the solvent. Thus, we have stepped up the computational strategy using a protocol based on metadynamics. Our approach has allowed dealing with protein motion and solvation during ligand binding and finally identifying the lowest energy binding modes of the most potent compound of the series, 4-decyl-pyrazolo[1,5-a]pyrimidin-7-one. PMID:22238423

  12. Differential Binding Models for Direct and Reverse Isothermal Titration Calorimetry.

    Science.gov (United States)

    Herrera, Isaac; Winnik, Mitchell A

    2016-03-10

    Isothermal titration calorimetry (ITC) is a technique to measure the stoichiometry and thermodynamics from binding experiments. Identifying an appropriate mathematical model to evaluate titration curves of receptors with multiple sites is challenging, particularly when the stoichiometry or binding mechanism is not available. In a recent theoretical study, we presented a differential binding model (DBM) to study calorimetry titrations independently of the interaction among the binding sites (Herrera, I.; Winnik, M. A. J. Phys. Chem. B 2013, 117, 8659-8672). Here, we build upon our DBM and show its practical application to evaluate calorimetry titrations of receptors with multiple sites independently of the titration direction. Specifically, we present a set of ordinary differential equations (ODEs) with the general form d[S]/dV that can be integrated numerically to calculate the equilibrium concentrations of free and bound species S at every injection step and, subsequently, to evaluate the volume-normalized heat signal (δQ(V) = δq/dV) of direct and reverse calorimetry titrations. Additionally, we identify factors that influence the shape of the titration curve and can be used to optimize the initial concentrations of titrant and analyte. We demonstrate the flexibility of our updated DBM by applying these differentials and a global regression analysis to direct and reverse calorimetric titrations of gadolinium ions with multidentate ligands of increasing denticity, namely, diglycolic acid (DGA), citric acid (CIT), and nitrilotriacetic acid (NTA), and use statistical tests to validate the stoichiometries for the metal-ligand pairs studied.

  13. Shedding lights on the flexible-armed porphyrins: Human telomeric G4 DNA interaction and cell photocytotoxicity research.

    Science.gov (United States)

    Sun, Xiang-Yu; Zhao, Ping; Jin, Shu-Fang; Liu, Min-Chao; Wang, Xia-Hong; Huang, Yu-Min; Cheng, Zhen-Feng; Yan, Si-Qi; Li, Yan-Yu; Chen, Ya-Qing; Zhong, Yan-Mei

    2017-08-01

    DNA polymorphism exerts a fascination on a large scientific community. Without crystallographic structural data, clarification of the binding modes between G-quadruplex (G4) and ligand (complex) is a challenging job. In the present work, three porphyrin compounds with different flexible carbon chains (arms) were designed, synthesized and characterized. Their binding, folding and stabilizing abilities to human telomeric G4 DNA structures were comparatively researched. Positive charges at the end of the flexible carbon chains seem to be favorable for the DNA-porphyrin interactions, which were evidenced by the spectral results and further confirmed by the molecular docking calculations. Biological function analysis demonstrated that these porphyrins show no substantial inhibition to Hela, A549 and BEL 7402 cancer cell lines under dark while exhibit broad inhibition under visible light. This significantly enhanced photocytotoxicity relative to the dark control is an essential property of photochemotherapeutic agents. The feature of the flexible arms emerges as critical influencing factors in the cell photocytotoxicity. Moreover, an ROS-mediated mitochondrial dysfunction pathway was suggested for the cell apoptosis induced by these flexible-armed porphyrins. It is found that the porphyrins with positive charges located at the end of the flexible arms represent an exciting opportunity for photochemotherapeutic anti-cancer drug design. Copyright © 2017. Published by Elsevier B.V.

  14. [3]tetrahydrotrazodone binding. Association with serotonin binding sites

    International Nuclear Information System (INIS)

    Kendall, D.A.; Taylor, D.P.; Enna, S.J.

    1983-01-01

    High (17 nM) and low (603 nM) affinity binding sites for [ 3 ]tetrahydrotrazodone ([ 3 ] THT), a biologically active analogue of trazodone, have been identified in rat brain membranes. The substrate specificity, concentration, and subcellular and regional distributions of these sites suggest that they may represent a component of the serotonin transmitter system. Pharmacological analysis of [ 3 ]THT binding, coupled with brain lesion and drug treatment experiments, revealed that, unlike other antidepressants, [ 3 ] THT does not attach to either a biogenic amine transporter or serotonin binding sites. Rather, it would appear that [ 3 ]THT may be an antagonist ligand for the serotonin binding site. This probe may prove of value in defining the mechanism of action of trazodone and in further characterizing serotonin receptors

  15. Protein binding of psychotropic agents

    International Nuclear Information System (INIS)

    Hassan, H.A.

    1990-01-01

    Based upon fluorescence measurements, protein binding of some psychotropic agents (chlorpromazine, promethazine, and trifluoperazine) to human IgG and HSA was studied in aqueous cacodylate buffer, PH7. The interaction parameters determined from emission quenching of the proteins. The interaction parameters determined include the equilibrium constant (K), calculated from equations derived by Borazan and coworkers, the number of binding sites (n) available to the monomer molecules on a single protein molecule. The results revealed a high level of affinity, as reflected by high values of K, and the existence of specific binding sites, since a limited number of n values are obtained. 39 tabs.; 37 figs.; 83 refs

  16. Research into Flexibility Services. Final Report

    International Nuclear Information System (INIS)

    2005-03-01

    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

  17. Mechanism of the G-protein mimetic nanobody binding to a muscarinic G-protein-coupled receptor.

    Science.gov (United States)

    Miao, Yinglong; McCammon, J Andrew

    2018-03-20

    Protein-protein binding is key in cellular signaling processes. Molecular dynamics (MD) simulations of protein-protein binding, however, are challenging due to limited timescales. In particular, binding of the medically important G-protein-coupled receptors (GPCRs) with intracellular signaling proteins has not been simulated with MD to date. Here, we report a successful simulation of the binding of a G-protein mimetic nanobody to the M 2 muscarinic GPCR using the robust Gaussian accelerated MD (GaMD) method. Through long-timescale GaMD simulations over 4,500 ns, the nanobody was observed to bind the receptor intracellular G-protein-coupling site, with a minimum rmsd of 2.48 Å in the nanobody core domain compared with the X-ray structure. Binding of the nanobody allosterically closed the orthosteric ligand-binding pocket, being consistent with the recent experimental finding. In the absence of nanobody binding, the receptor orthosteric pocket sampled open and fully open conformations. The GaMD simulations revealed two low-energy intermediate states during nanobody binding to the M 2 receptor. The flexible receptor intracellular loops contribute remarkable electrostatic, polar, and hydrophobic residue interactions in recognition and binding of the nanobody. These simulations provided important insights into the mechanism of GPCR-nanobody binding and demonstrated the applicability of GaMD in modeling dynamic protein-protein interactions.

  18. Identification of the quinolinedione inhibitor binding site in Cdc25 phosphatase B through docking and molecular dynamics simulations

    Science.gov (United States)

    Ge, Yushu; van der Kamp, Marc; Malaisree, Maturos; Liu, Dan; Liu, Yi; Mulholland, Adrian J.

    2017-11-01

    Cdc25 phosphatase B, a potential target for cancer therapy, is inhibited by a series of quinones. The binding site and mode of quinone inhibitors to Cdc25B remains unclear, whereas this information is important for structure-based drug design. We investigated the potential binding site of NSC663284 [DA3003-1 or 6-chloro-7-(2-morpholin-4-yl-ethylamino)-quinoline-5, 8-dione] through docking and molecular dynamics simulations. Of the two main binding sites suggested by docking, the molecular dynamics simulations only support one site for stable binding of the inhibitor. Binding sites in and near the Cdc25B catalytic site that have been suggested previously do not lead to stable binding in 50 ns molecular dynamics (MD) simulations. In contrast, a shallow pocket between the C-terminal helix and the catalytic site provides a favourable binding site that shows high stability. Two similar binding modes featuring protein-inhibitor interactions involving Tyr428, Arg482, Thr547 and Ser549 are identified by clustering analysis of all stable MD trajectories. The relatively flexible C-terminal region of Cdc25B contributes to inhibitor binding. The binding mode of NSC663284, identified through MD simulation, likely prevents the binding of protein substrates to Cdc25B. The present results provide useful information for the design of quinone inhibitors and their mechanism of inhibition.

  19. Identification of the quinolinedione inhibitor binding site in Cdc25 phosphatase B through docking and molecular dynamics simulations.

    Science.gov (United States)

    Ge, Yushu; van der Kamp, Marc; Malaisree, Maturos; Liu, Dan; Liu, Yi; Mulholland, Adrian J

    2017-11-01

    Cdc25 phosphatase B, a potential target for cancer therapy, is inhibited by a series of quinones. The binding site and mode of quinone inhibitors to Cdc25B remains unclear, whereas this information is important for structure-based drug design. We investigated the potential binding site of NSC663284 [DA3003-1 or 6-chloro-7-(2-morpholin-4-yl-ethylamino)-quinoline-5, 8-dione] through docking and molecular dynamics simulations. Of the two main binding sites suggested by docking, the molecular dynamics simulations only support one site for stable binding of the inhibitor. Binding sites in and near the Cdc25B catalytic site that have been suggested previously do not lead to stable binding in 50 ns molecular dynamics (MD) simulations. In contrast, a shallow pocket between the C-terminal helix and the catalytic site provides a favourable binding site that shows high stability. Two similar binding modes featuring protein-inhibitor interactions involving Tyr428, Arg482, Thr547 and Ser549 are identified by clustering analysis of all stable MD trajectories. The relatively flexible C-terminal region of Cdc25B contributes to inhibitor binding. The binding mode of NSC663284, identified through MD simulation, likely prevents the binding of protein substrates to Cdc25B. The present results provide useful information for the design of quinone inhibitors and their mechanism of inhibition.

  20. Moderate daily exercise activates metabolic flexibility to prevent prenatally induced obesity.

    Science.gov (United States)

    Miles, Jennifer L; Huber, Korinna; Thompson, Nichola M; Davison, Michael; Breier, Bernhard H

    2009-01-01

    Obesity and its associated comorbidities are of major worldwide concern. It is now recognized that there are a number of metabolically distinct pathways of obesity development. The present paper investigates the effect of moderate daily exercise on the underlying mechanisms of one such pathway to obesity, through interrogation of metabolic flexibility. Pregnant Wistar rats were either fed chow ad libitum or undernourished throughout pregnancy, generating control or intrauterine growth restricted (IUGR) offspring, respectively. At 250 d of age, dual-emission x-ray absorptiometry scans and plasma analyses showed that moderate daily exercise, in the form of a measured amount of wheel running (56 m/d), prevented the development of obesity consistently observed in nonexercised IUGR offspring. Increased plasma C-peptide and hepatic atypical protein kinase Czeta levels explained increased glucose uptake and increased hepatic glycogen storage in IUGR offspring. Importantly, whereas circulating levels of retinol binding protein 4 were elevated in obese, nonexercised IUGR offspring, indicative of glucose sparing without exercise, retinol binding protein 4 levels were normalized in the exercised IUGR group. These data suggest that IUGR offspring have increased flexibility of energy storage and use and that moderate daily exercise prevents obesity development through activation of distinct pathways of energy use. Thus, despite a predisposition to develop obesity under sedentary conditions, obesity development was prevented in IUGR offspring when exercise was available. These results emphasize the importance of tailored lifestyle changes that activate distinct pathways of metabolic flexibility for obesity prevention.

  1. Switch-loop flexibility affects transport of large drugs by the promiscuous AcrB multidrug efflux transporter.

    Science.gov (United States)

    Cha, Hi-jea; Müller, Reinke T; Pos, Klaas M

    2014-08-01

    Multidrug efflux transporters recognize a variety of structurally unrelated compounds for which the molecular basis is poorly understood. For the resistance nodulation and cell division (RND) inner membrane component AcrB of the AcrAB-TolC multidrug efflux system from Escherichia coli, drug binding occurs at the access and deep binding pockets. These two binding areas are separated by an 11-amino-acid-residue-containing switch loop whose conformational flexibility is speculated to be essential for drug binding and transport. A G616N substitution in the switch loop has a distinct and local effect on the orientation of the loop and on the ability to transport larger drugs. Here, we report a distinct phenotypical pattern of drug recognition and transport for the G616N variant, indicating that drug substrates with minimal projection areas of >70 Å(2) are less well transported than other substrates. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  2. Superresolution microscopy with transient binding.

    Science.gov (United States)

    Molle, Julia; Raab, Mario; Holzmeister, Susanne; Schmitt-Monreal, Daniel; Grohmann, Dina; He, Zhike; Tinnefeld, Philip

    2016-06-01

    For single-molecule localization based superresolution, the concentration of fluorescent labels has to be thinned out. This is commonly achieved by photophysically or photochemically deactivating subsets of molecules. Alternatively, apparent switching of molecules can be achieved by transient binding of fluorescent labels. Here, a diffusing dye yields bright fluorescent spots when binding to the structure of interest. As the binding interaction is weak, the labeling is reversible and the dye ligand construct diffuses back into solution. This approach of achieving superresolution by transient binding (STB) is reviewed in this manuscript. Different realizations of STB are discussed and compared to other localization-based superresolution modalities. We propose the development of labeling strategies that will make STB a highly versatile tool for superresolution microscopy at highest resolution. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Reliability analysis of stiff versus flexible piping

    International Nuclear Information System (INIS)

    Lu, S.C.

    1985-01-01

    The overall objective of this research project is to develop a technical basis for flexible piping designs which will improve piping reliability and minimize the use of pipe supports, snubbers, and pipe whip restraints. The current study was conducted to establish the necessary groundwork based on the piping reliability analysis. A confirmatory piping reliability assessment indicated that removing rigid supports and snubbers tends to either improve or affect very little the piping reliability. The authors then investigated a couple of changes to be implemented in Regulatory Guide (RG) 1.61 and RG 1.122 aimed at more flexible piping design. They concluded that these changes substantially reduce calculated piping responses and allow piping redesigns with significant reduction in number of supports and snubbers without violating ASME code requirements. Furthermore, the more flexible piping redesigns are capable of exhibiting reliability levels equal to or higher than the original stiffer design. An investigation of the malfunction of pipe whip restraints confirmed that the malfunction introduced higher thermal stresses and tended to reduce the overall piping reliability. Finally, support and component reliabilities were evaluated based on available fragility data. Results indicated that the support reliability usually exhibits a moderate decrease as the piping flexibility increases. Most on-line pumps and valves showed an insignificant reduction in reliability for a more flexible piping design

  4. Transcervical heller myotomy using flexible endoscopy.

    Science.gov (United States)

    Spaun, Georg O; Dunst, Christy M; Arnold, Brittany N; Martinec, Danny V; Cassera, Maria A; Swanström, Lee L

    2010-12-01

    Esophageal achalasia is most commonly treated by laparoscopic myotomy. Transesophageal approaches using flexible endoscopy have recently been described. We hypothesized that using techniques and flexible instruments from our NOTES experience through a small cervical incision would be a safer and less traumatic route for esophageal myotomy. The purpose of this study was to evaluate the feasibility, safety, and success rate of using flexible endoscopes to perform anterior or posterior Heller myotomy via a transcervical approach. This animal (porcine) and human cadaver study was conducted at the Legacy Research and Technology Center. Mediastinal operations on ten live, anesthetized pigs and two human cadavers were performed using standard flexible endoscopes through a small incision at the supra-sternal notch. The esophagus was dissected to the phreno-esophageal junction using balloon dilatation in the peri-esophageal space followed by either anterior or posterior distal esophageal myotomy. Success rate was recorded of esophageal dissection to the diaphragm and proximal stomach, anterior and posterior myotomy, perforation, and complication rates. Dissection of the esophagus to the diaphragm and performing esophageal myotomy was achieved in 100% of attempts. Posterior Heller myotomy was always extendable onto the gastric wall, while anterior gastric extension of the myotomy was found to be more difficult (4/4 and 2/8, respectively; P = 0.061). Heller myotomy through a small cervical incision using flexible endoscopes is feasible. A complete Heller myotomy was performed with a higher success rate posteriorly possibly due to less anatomic interference.

  5. Experimental Research on Fluid Coupling Flexible Actuator

    Directory of Open Access Journals (Sweden)

    Xiangli Zeng

    2018-02-01

    Full Text Available In the field of micromechanics, piezoelectric actuator has attracted great attention for its high-frequency response, high displacement resolution, and high output force. However, its prospect of practical application has been largely limited by the displacement of micrometer. A fluid coupling flexible actuator was proposed, which utilizes resonance to enlarge the output displacement. The actuator uses a piezoelectric oscillator as an excitation source, fluid as the transmission medium and a flexible diaphragm for the displacement output. On the condition that the fluid is inviscid and incompressible, mathematical formulation of the membrane vibration theory has been analyzed. Then, the prototype is made. The displacement is amplified 21 times to 1.106 mm when driving frequency is 127 Hz. The flexible diaphragm appears the largest displacement output when driving frequency is close to one of the system’s natural frequency. Then, the points with zero amplitude form a circle on the surface of flexible diaphragm and the movement direction of the flexible diaphragm is opposite on different sides of the circle. In fact, rather than vibrates at the first resonance frequency, the membrane in the essay is vibrating at a certain higher-order resonance frequency. The experimental results are mainly consistent with the theoretical analysis.

  6. Flexible graphene bio-nanosensor for lactate.

    Science.gov (United States)

    Labroo, Pratima; Cui, Yue

    2013-03-15

    The development of a flexible nanosensor for detecting lactate could expand opportunities for using graphene, both in fundamental studies for a variety of device platforms and in practical applications. Graphene is a delicate single-layer, two-dimensional network of carbon atoms with ultrasensitive sensing capabilities. Lactic acid is important for clinical analysis, sports medicine, and the food industry. Recently, wearable and flexible bioelectronics on plastics have attracted great interest for healthcare, sports and defense applications due to their advantages of being light-weight, bendable, or stretchable. Here, we demonstrate for the first time the development of a flexible graphene-based bio-nanosensor to detect lactate. Our results show that flexible lactate biosensors can be fabricated on a variety of plastic substrates. The sensor can detect lactate sensitively from 0.08 μM to 20 μM with a fast steady-state measuring time of 2s. The sensor can also detect lactate under different mechanical bending conditions, the sensor response decreased as the bending angle and number of bending repetitions increased. We anticipate that these results could open exciting opportunities for fundamental studies of flexible graphene bioelectronics by using other bioreceptors, as well as a variety of wearable, implantable, real-time, or on-site applications in fields ranging from clinical analysis to defense. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. Flexible heat pipes with integrated bioinspired design

    Directory of Open Access Journals (Sweden)

    Chao Yang

    2015-02-01

    Full Text Available In this work we report the facile fabrication and performance evaluation of flexible heat pipes that have integrated bioinspired wick structures and flexible polyurethane polymer connector design between the copper condenser and evaporator. Inside the heat pipe, a bioinspired superhydrophilic strong-base-oxidized copper mesh with multi-scale micro/nano-structures was used as the wicking material and deionized water was selected as working fluid. Thermal resistances of the fabricated flexible heat pipes charged with different filling ratios were measured under thermal power inputs ranging from 2 W to 12 W while the device was bent at different angles. The fabricated heat pipes with a 30% filling ratio demonstrated a low thermal resistance less than 0.01 K/W. Compared with the vertically oriented straight heat pipes, bending from 30° up to 120° has negligible influence on the heat-transfer performance. Furthermore, repeated heating tests indicated that the fabricated flexible heat pipes have consistent and reliable heat-transfer performance, thus would have important applications for advanced thermal management in three dimensional and flexible electronic devices.

  8. The value of flexibility in conservation financing.

    Science.gov (United States)

    Lennox, Gareth D; Fargione, Joseph; Spector, Sacha; Williams, Gwyn; Armsworth, Paul R

    2017-06-01

    Land-acquisition strategies employed by conservation organizations vary in their flexibility. Conservation-planning theory largely fails to reflect this by presenting models that are either extremely inflexible-parcel acquisitions are irreversible and budgets are fixed-or extremely flexible-previously acquired parcels can readily be sold. This latter approach, the selling of protected areas, is infeasible or problematic in many situations. We considered the value to conservation organizations of increasing the flexibility of their land-acquisition strategies through their approach to financing deals. Specifically, we modeled 2 acquisition-financing methods commonly used by conservation organizations: borrowing and budget carry-over. Using simulated data, we compared results from these models with those from an inflexible fixed-budget model and an extremely flexible selling model in which previous acquisitions could be sold to fund new acquisitions. We then examined 3 case studies of how conservation organizations use borrowing and budget carry-over in practice. Model comparisons showed that borrowing and budget carry-over always returned considerably higher rewards than the fixed-budget model. How they performed relative to the selling model depended on the relative conservation value of past acquisitions. Both the models and case studies showed that incorporating flexibility through borrowing or budget carry-over gives conservation organizations the ability to purchase parcels of higher conservation value than when budgets are fixed without the problems associated with the selling of protected areas. © 2016 Society for Conservation Biology.

  9. Propulsion via flexible flapping in granular media

    Science.gov (United States)

    Peng, Zhiwei; Ding, Yang; Pietrzyk, Kyle; Elfring, Gwynn; Pak, On Shun

    2017-11-01

    Biological locomotion in nature is often achieved by the interaction between a flexible body and its surrounding medium. The interaction of a flexible body with granular media is less understood compared with viscous fluids partially due to its complex rheological properties. In this work, we explore the effect of flexibility on granular propulsion by considering a simple mechanical model in which a rigid rod is connected to a torsional spring that is under a displacement actuation using a granular resistive force theory. Through a combined numerical and asymptotic investigation, we characterize the propulsive dynamics of such a flexible flapper in relation to the actuation amplitude and spring stiffness, and we compare these dynamics with those observed in a viscous fluid. In addition, we demonstrate that the maximum possible propulsive force can be obtained in the steady propulsion limit with a finite spring stiffness and large actuation amplitude. These results may apply to the development of synthetic locomotive systems that exploit flexibility to move through complex terrestrial media. Funding for Z.P. and Y.D. was partially provided by NSFC 394 Grant No. 11672029 and NSAF-NSFC Grant No. U1530401.

  10. Interfacial characterization of flexible hybrid electronics

    Science.gov (United States)

    Najafian, Sara; Amirkhizi, Alireza V.; Stapleton, Scott

    2018-03-01

    Flexible Hybrid Electronics (FHEs) are the new generation of electronics combining flexible plastic film substrates with electronic devices. Besides the electrical features, design improvements of FHEs depend on the prediction of their mechanical and failure behavior. Debonding of electronic components from the flexible substrate is one of the most common and critical failures of these devices, therefore, the experimental determination of material and interface properties is of great importance in the prediction of failure mechanisms. Traditional interface characterization involves isolated shear and normal mode tests such as the double cantilever beam (DCB) and end notch flexure (ENF) tests. However, due to the thin, flexible nature of the materials and manufacturing restrictions, tests mirroring traditional interface characterization experiments may not always be possible. The ideal goal of this research is to design experiments such that each mode of fracture is isolated. However, due to the complex nonlinear nature of the response and small geometries of FHEs, design of the proper tests to characterize the interface properties can be significantly time and cost consuming. Hence numerical modeling has been implemented to design these novel characterization experiments. This research involves loading case and specimen geometry parametric studies using numerical modeling to design future experiments where either shear or normal fracture modes are dominant. These virtual experiments will provide a foundation for designing similar tests for many different types of flexible electronics and predicting the failure mechanism independent of the specific FHE materials.

  11. Calculations of proton-binding thermodynamics in proteins.

    Science.gov (United States)

    Beroza, P; Case, D A

    1998-01-01

    Computational models of proton binding can range from the chemically complex and statistically simple (as in the quantum calculations) to the chemically simple and statistically complex. Much progress has been made in the multiple-site titration problem. Calculations have improved with the inclusion of more flexibility in regard to both the geometry of the proton binding and the larger scale protein motions associated with titration. This article concentrated on the principles of current calculations, but did not attempt to survey their quantitative performance. This is (1) because such comparisons are given in the cited papers and (2) because continued developments in understanding conformational flexibility and interaction energies will be needed to develop robust methods with strong predictive power. Nevertheless, the advances achieved over the past few years should not be underestimated: serious calculations of protonation behavior and its coupling to conformational change can now be confidently pursued against a backdrop of increasing understanding of the strengths and limitations of such models. It is hoped that such theoretical advances will also spur renewed experimental interest in measuring both overall titration curves and individual pKa values or pKa shifts. Exploration of the shapes of individual titration curves (as measured by Hill coefficients and other parameters) would also be useful in assessing the accuracy of computations and in drawing connections to functional behavior.

  12. Intrinsic flexibility of porous materials; theory, modelling and the flexibility window of the EMT zeolite framework

    International Nuclear Information System (INIS)

    Fletcher, Rachel E.; Wells, Stephen A.; Leung, Ka Ming; Edwards, Peter P.; Sartbaeva, Asel

    2015-01-01

    Framework materials possess intrinsic flexibility which can be investigated using geometric simulation. We review framework flexibility properties in energy materials and present novel results on the flexibility window of the EMT zeolite framework containing 18-crown-6 ether as a structure directing agent (SDA). Framework materials have structures containing strongly bonded polyhedral groups of atoms connected through their vertices. Typically the energy cost for variations of the inter-polyhedral geometry is much less than the cost of distortions of the polyhedra themselves – as in the case of silicates, where the geometry of the SiO 4 tetrahedral group is much more strongly constrained than the Si—O—Si bridging angle. As a result, framework materials frequently display intrinsic flexibility, and their dynamic and static properties are strongly influenced by low-energy collective motions of the polyhedra. Insight into these motions can be obtained in reciprocal space through the ‘rigid unit mode’ (RUM) model, and in real-space through template-based geometric simulations. We briefly review the framework flexibility phenomena in energy-relevant materials, including ionic conductors, perovskites and zeolites. In particular we examine the ‘flexibility window’ phenomenon in zeolites and present novel results on the flexibility window of the EMT framework, which shed light on the role of structure-directing agents. Our key finding is that the crown ether, despite its steric bulk, does not limit the geometric flexibility of the framework

  13. 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…

  14. 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

  15. 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…

  16. 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…

  17. Docking of flexible ligands to flexible receptors in solution by molecular dynamics simulation

    NARCIS (Netherlands)

    Mangoni, R; Roccatano, D; Di Nola, A

    1999-01-01

    In this paper, a method of simulating the docking of small flexible ligands to flexible receptors in water is reported. The method is based on molecular dynamics simulations and is an extension of an algorithm previously reported by Di Nola et al, (Di Nola et al,, Proteins 1994;19:174-182), The

  18. Mechanistic modelling of weak interlayers in flexible and semi-flexible road pavements: Part 2

    CSIR Research Space (South Africa)

    De Beer, Morris

    2012-04-01

    Full Text Available This paper (Part 2 of a two-part set of papers) discusses models and illustrates the adverse effects of weak layers, interlayers, laminations and/or weak interfaces in flexible and semi-flexible pavements, also incorporating lightly cemented layers...

  19. Local Flexibility Market Design for Aggregators Providing Multiple Flexibility Services at Distribution Network Level

    Directory of Open Access Journals (Sweden)

    Pol Olivella-Rosell

    2018-04-01

    Full Text Available This paper presents a general description of local flexibility markets as a market-based management mechanism for aggregators. The high penetration of distributed energy resources introduces new flexibility services like prosumer or community self-balancing, congestion management and time-of-use optimization. This work is focused on the flexibility framework to enable multiple participants to compete for selling or buying flexibility. In this framework, the aggregator acts as a local market operator and supervises flexibility transactions of the local energy community. Local market participation is voluntary. Potential flexibility stakeholders are the distribution system operator, the balance responsible party and end-users themselves. Flexibility is sold by means of loads, generators, storage units and electric vehicles. Finally, this paper presents needed interactions between all local market stakeholders, the corresponding inputs and outputs of local market operation algorithms from participants and a case study to highlight the application of the local flexibility market in three scenarios. The local market framework could postpone grid upgrades, reduce energy costs and increase distribution grids’ hosting capacity.

  20. Skill Flexibility among Schoolteachers: Operationalization and Organizational Implications.

    Science.gov (United States)

    Rosenblatt, Zehava; Inbal, Batia

    1999-01-01

    Investigates effects of skill flexibility on Israeli secondary teachers' work attitudes and job performance. Both role and functional flexibility were associated with improved teachers' work performance; role flexibility is linked to high organizational commitment and low powerlessness. Principals appreciate skill flexibility, but organizational…

  1. Organizing for Flexibility: Addressing Dynamic Capabilities and Organization Design

    OpenAIRE

    van der Weerdt, Niels; Volberda, Henk; Verwaal, Ernst; Stienstra, Marten

    2014-01-01

    The increasingly dynamic nature of organizational environments has led the research community to study organizational flexibility. Although the research literature stresses the complexity of the organizational flexibility construct, it lacks a comprehensive empirical study addressing the relationships among various dimensions of organizational flexibility. This chapter develops a theoretical framework specifying the linkages between types of flexibility and organization design characteristics...

  2. Flexible labour strategy in the Dutch automotive industry

    NARCIS (Netherlands)

    van Riemsdijk, Maarten; de Leede, 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

  3. Binding Ligand Prediction for Proteins Using Partial Matching of Local Surface Patches

    Directory of Open Access Journals (Sweden)

    Lee Sael

    2010-12-01

    Full Text Available Functional elucidation of uncharacterized protein structures is an important task in bioinformatics. We report our new approach for structure-based function prediction which captures local surface features of ligand binding pockets. Function of proteins, specifically, binding ligands of proteins, can be predicted by finding similar local surface regions of known proteins. To enable partial comparison of binding sites in proteins, a weighted bipartite matching algorithm is used to match pairs of surface patches. The surface patches are encoded with the 3D Zernike descriptors. Unlike the existing methods which compare global characteristics of the protein fold or the global pocket shape, the local surface patch method can find functional similarity between non-homologous proteins and binding pockets for flexible ligand molecules. The proposed method improves prediction results over global pocket shape-based method which was previously developed by our group.

  4. Binding ligand prediction for proteins using partial matching of local surface patches.

    Science.gov (United States)

    Sael, Lee; Kihara, Daisuke

    2010-01-01

    Functional elucidation of uncharacterized protein structures is an important task in bioinformatics. We report our new approach for structure-based function prediction which captures local surface features of ligand binding pockets. Function of proteins, specifically, binding ligands of proteins, can be predicted by finding similar local surface regions of known proteins. To enable partial comparison of binding sites in proteins, a weighted bipartite matching algorithm is used to match pairs of surface patches. The surface patches are encoded with the 3D Zernike descriptors. Unlike the existing methods which compare global characteristics of the protein fold or the global pocket shape, the local surface patch method can find functional similarity between non-homologous proteins and binding pockets for flexible ligand molecules. The proposed method improves prediction results over global pocket shape-based method which was previously developed by our group.

  5. Switch loop flexibility affects substrate transport of the AcrB efflux pump

    International Nuclear Information System (INIS)

    Muller, Reinke T.; Travers, Timothy; Cha, Hi-jea; Phillips, Joshua L.

    2017-01-01

    The functionally important switch-loop of the trimeric multidrug transporter AcrB separates the access and deep drug binding pockets in every protomer. This loop, comprising 11 amino acid residues, has been shown to be crucial for substrate transport, as drugs have to travel past the loop to reach the deep binding pocket and from there are transported outside the cell via the connected AcrA and TolC channels. It contains four symmetrically arranged glycine residues suggesting that flexibility is a key feature for pump activity. Upon combinatorial substitution of these glycine residues to proline, functional and structural asymmetry was observed. Proline substitutions on the PC1 proximal side completely abolished transport and reduced backbone flexibility of the switch loop, which adopted a conformation restricting the pathway towards the deep binding pocket. Here, two phenylalanine residues located adjacent to the substitution sensitive glycine residues play a role in blocking the pathway upon rigidification of the loop, since the removal of the phenyl rings from the rigid loop restores drug transport activity.

  6. 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. PsycINFO Database Record (c) 2008 APA, all rights reserved.

  7. Methods for fabrication of flexible hybrid electronics

    Science.gov (United States)

    Street, Robert A.; Mei, Ping; Krusor, Brent; Ready, Steve E.; Zhang, Yong; Schwartz, David E.; Pierre, Adrien; Doris, Sean E.; Russo, Beverly; Kor, Siv; Veres, Janos

    2017-08-01

    Printed and flexible hybrid electronics is an emerging technology with potential applications in smart labels, wearable electronics, soft robotics, and prosthetics. Printed solution-based materials are compatible with plastic film substrates that are flexible, soft, and stretchable, thus enabling conformal integration with non-planar objects. In addition, manufacturing by printing is scalable to large areas and is amenable to low-cost sheet-fed and roll-to-roll processes. FHE includes display and sensory components to interface with users and environments. On the system level, devices also require electronic circuits for power, memory, signal conditioning, and communications. Those electronic components can be integrated onto a flexible substrate by either assembly or printing. PARC has developed systems and processes for realizing both approaches. This talk presents fabrication methods with an emphasis on techniques recently developed for the assembly of off-the-shelf chips. A few examples of systems fabricated with this approach are also described.

  8. Analytical and numerical modeling for flexible pipes

    Science.gov (United States)

    Wang, Wei; Chen, Geng

    2011-12-01

    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. Granular flow down a flexible inclined plane

    Directory of Open Access Journals (Sweden)

    Sonar Prasad

    2017-01-01

    Full Text Available Discrete and continuous systems are commonly studied individually, but seldom together. Indeed, granular flows are typically studied through flows over a rigid base. Here, we investigate the behaviour of granular flows over an inclined, flexible base. The flexible base is modeled as a rigid platform mounted on springs and has one degree of freedom. The base vibrations are introduced by the flow. We simulate such flows through a discrete element method and compare with experiments. We find that a flexible base increased the upper limit of the inclination up to which a steady flow is possible by at least 3 degrees. This stabilized zone may have important implications in applications such as conveyor belts and chutes.

  10. Modeling and control of flexible space structures

    Science.gov (United States)

    Wie, B.; Bryson, A. E., Jr.

    1981-01-01

    The effects of actuator and sensor locations on transfer function zeros are investigated, using uniform bars and beams as generic models of flexible space structures. It is shown how finite element codes may be used directly to calculate transfer function zeros. The impulse response predicted by finite-dimensional models is compared with the exact impulse response predicted by the infinite dimensional models. It is shown that some flexible structures behave as if there were a direct transmission between actuator and sensor (equal numbers of zeros and poles in the transfer function). Finally, natural damping models for a vibrating beam are investigated since natural damping has a strong influence on the appropriate active control logic for a flexible structure.

  11. 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...

  12. Plasma jet printing for flexible substrates

    Energy Technology Data Exchange (ETDEWEB)

    Gandhiraman, Ram P.; Singh, Eric; Diaz-Cartagena, Diana C.; Koehne, Jessica; Meyyappan, M. [Center for Nanotechnology, NASA Ames Research Center, Moffett Field, California 94035 (United States); Nordlund, Dennis [Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, Menlo Park, California 94025 (United States)

    2016-03-21

    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.

  13. 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.

  14. A flexible modelling software for data acquisition

    International Nuclear Information System (INIS)

    Shu Yantai; Chen Yanhui; Yang Songqi; Liu Genchen

    1992-03-01

    A flexible modelling software for data acquisition is based on an event-driven simulator. It can be used to simulate a wide variety of systems which can be modelled as open queuing networks. The main feature of the software is its flexibility to evaluate the performance of various data acquisition system, whether pulsed or not. The flexible features of this software as follow: The user can choose the number of processors in the model and the route which every job takes to move the model. the service rate of a processor is automatically adapted. The simulator has a pipe-line mechanism. A job can be divided into several segments and a processor may be used as a compression component etc. Some modelling techniques and applications of this software in plasma physics laboratories are also presented

  15. 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.

  16. 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

  17. 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

  18. To bind or not to bind? Different temporal binding effects from voluntary pressing and releasing actions.

    Science.gov (United States)

    Zhao, Ke; Chen, Yu-Hsin; Yan, Wen-Jing; Fu, Xiaolan

    2013-01-01

    Binding effect refers to the perceptual attraction between an action and an outcome leading to a subjective compression of time. Most studies investigating binding effects exclusively employ the "pressing" action without exploring other types of actions. The present study addresses this issue by introducing another action, releasing action or the voluntary lifting of the finger/wrist, to investigate the differences between voluntary pressing and releasing actions. Results reveal that releasing actions led to robust yet short-lived temporal binding effects, whereas pressing condition had steady temporal binding effects up to super-seconds. The two actions also differ in sensitivity to changes in temporal contiguity and contingency, which could be attributed to the difference in awareness of action. Extending upon current models of "willed action," our results provide insights from a temporal point of view and support the concept of a dual system consisting of predictive motor control and top-down mechanisms.

  19. Free-Standing, Flexible, Superomniphobic Films.

    Science.gov (United States)

    Vahabi, Hamed; Wang, Wei; Movafaghi, Sanli; Kota, Arun K

    2016-08-31

    Fabrication of most superomniphobic surfaces requires complex process conditions or specialized and expensive equipment or skilled personnel. In order to circumvent these issues and make them end-user-friendly, we developed the free-standing, flexible, superomniphobic films. These films can be stored and delivered to the end-users, who can readily attach them to virtually any surface (even irregular shapes) and impart superomniphobicity. The hierarchical structure, the re-entrant texture, and the low solid surface energy render our films superomniphobic for a wide variety of liquids. We demonstrate that our free-standing, flexible, superomniphobic films have applications in enhanced chemical resistance and enhanced weight bearing.

  20. 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.

  1. Electro Spray Method for Flexible Display

    Science.gov (United States)

    2016-05-12

    AFRL-AFOSR-JP-TR-2016-0095 Electro Spray Method for Flexible Display Yukiharu Uraoka NARA INSTITUTE OF SCIENCE AND TECHNOLOGY Final Report 11/26/2016...DATES COVERED (From - To)  20 Mar 2013 to 19 May 2016 4. TITLE AND SUBTITLE Electro Spray Method for Flexible Display 5a.  CONTRACT NUMBER 5b.  GRANT...NUMBER FA2386-13-1-4024 5c.  PROGRAM ELEMENT NUMBER 61102F 6. AUTHOR(S) Yukiharu Uraoka 5d.  PROJECT NUMBER 5e.  TASK NUMBER 5f.   WORK UNIT NUMBER 7

  2. Cold plasma decontamination using flexible jet arrays

    Science.gov (United States)

    Konesky, Gregory

    2010-04-01

    Arrays of atmospheric discharge cold plasma jets have been used to decontaminate surfaces of a wide range of microorganisms quickly, yet not damage that surface. Its effectiveness in decomposing simulated chemical warfare agents has also been demonstrated, and may also find use in assisting in the cleanup of radiological weapons. Large area jet arrays, with short dwell times, are necessary for practical applications. Realistic situations will also require jet arrays that are flexible to adapt to contoured or irregular surfaces. Various large area jet array prototypes, both planar and flexible, are described, as is the application to atmospheric decontamination.

  3. 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

  4. On the concept of flexibility: A dual control perspective

    OpenAIRE

    Leeuw, A. C J; Volberda, Henk

    1996-01-01

    textabstractOrganizational flexibility has recently received much attention from researchers, management consultants and practitioners. In general, the term 'flexibility' has a positive connotation: flexible organizations are the better ones. However, the meaning of flexibility as well as its relation to the functioning of an organization is still ambiguous. This article develops a systematic and multidimensional picture of flexibility on the basis of views taken from the systems theory of co...

  5. LIGAND-BINDING SITES ON THE MYCOBACTERIUM TUBERCULOSIS UREASE

    Directory of Open Access Journals (Sweden)

    Lisnyak Yu. V.

    2017-10-01

    algorithm. To model the reduction in flexibility of allosteric pocket on modulator binding, the unperturbed normal modes are first calculated for the protein. The calculation is then repeated, each time perturbing one of the pockets in the protein. These results are combined with output from Fpocket in a support vector machine (SVM to predict allosteric pockets on proteins. The AlloSite server is similar to the AlloPred method in that it uses the Fpocket algorithm to elucidate allosteric pockets, whereas AlloPred uses an approach that combines flexibility with the Fpocket output. Results and discussion. By computational solvent mapping method FTSite, we have explored M.tuberculosis urease nonamer surface to find sites that tend to bind small organic molecular probes representing fragments of drug molecules with diverse hydrophobic and hydrophilic properties. The predicted three top ranked binding sites were situated at the interfaces between chains C and A, and chain G of neighbour trimer (and at equivalent locations in symmetrical trimers as well. A mapping of enzymes generally yields the most probable sites situated in a subsite of the enzyme active site. This was not the case for MTU which active sites were inaccessible for probes due to the closed conformation of the covering flap, and predicted binding sites were located not far from them at the entrance into a deep pocket. To explore their possible structural and functional role, we correlated the locations of predicted MTU binding sites and its ancillary pockets (which remain open and solvent exposed even while the flap is closed and indicated their partial overlapping. This overlapping may suggest that predicted sites are likely the intermediate binding sites responsible for recruiting a ligand to another binding site deeply buried in the protein. To examine the possibility that predicted binding sites are the sites for allostery binding we carried out the search for probable sites of allostery binding on MTU

  6. Flexible optical fiber sensor based on polyurethane

    DEFF Research Database (Denmark)

    Kaysir, Md Rejvi; Stefani, Alessio; Lwin, Richard

    Polyurethane (PU) based hollow core fibers are investigated as optical sensors. The flexibility of PU fibers makes it suitable for sensing mechanical perturbations. We fabricated a PU fiber using the fiber drawing method, characterized the fiber and experimentally demonstrated a simple way...... to measure deformation, in the form of applied pressure....

  7. Training Package Implementation: Innovative and Flexible Approaches.

    Science.gov (United States)

    Meyers, Dave; Blom, Kaaren

    The implementation of training packages (TPs) in Australian workplaces was examined through case studies of the use of TPs in nontraditional trade areas by six innovative registered training organizations (RTOs) across Australia. The study focused on the extent to which new and flexible approaches to learning, training delivery, and assessment…

  8. NextFlex Flexible Hybrid Electronics Manufacturing

    Science.gov (United States)

    2016-10-01

    of the power of silicon and the economies and unique capabilities of printed circuitry to form a new class of devices for the Internet of Things (IoT...innovative medical devices that can take Processor* Display* Memory + Polymer Solar Cell # Flexible Substrate Sensors* Antenna #Thin Film Battery

  9. Flexible Communication Platform for Crisis Management

    OpenAIRE

    Jiří Barta; Tomáš Ludík; Jiří Urbánek

    2013-01-01

    Topics Disaster and Emergency Management are highly debated among experts. Fast communication will help to deal with emergencies. Problem is with the network connection and data exchange. The paper suggests a solution, which allows possibilities and perspectives of new flexible communication platform to the protection of communication systems for crisis management. This platform is used for everyday communication and communication in crisis situations too.

  10. Innovation in wearable and flexible antennas

    CERN Document Server

    Khaleel, Haider

    2014-01-01

    This book covers the design, numerical simulation, state of the art fabrication processes, qualitative and quantitative tests, and measurement techniques of wearable and flexible antennas of various topologies, such as: Printed Monopoles, Micropoles and Microstrips. It serves as a vital reference source for scientists and engineers in this field.

  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. Step growth of two flexible ABf monomers

    DEFF Research Database (Denmark)

    Cameron, Colin; Fawcett, Allan H.; Hetherington, Cecil R.

    2000-01-01

    A three-dimensional lattice model was used to simulate the competition between the growth of hyperbranched structures and cycle formation that occurs when flexible ABf monomers undergo step growth. The monomers in the model are mapped onto several lattice sites. The effect of functionality...

  13. 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

  14. Is labour market flexibility harmful to innovation?

    NARCIS (Netherlands)

    Kleinknecht, A.H.

    1998-01-01

    In a neoclassical framework one can argue that unemployment can be reduced by means of institutional changes that allow for a better working of the labour market and, notably, by achieving downward wage flexibility. I argue that although various policy recommendations about removing labour market

  15. Towards Flexibility in Academic Labour Markets?

    Science.gov (United States)

    Nieuwenhuysen, John

    1985-01-01

    It is argued that Australia's relatively uniform and consistent academic salary structure and personnel policies should be more flexible and competitive in order to alleviate current problems of academic labor market stagnation, uneven faculty distribution, and other results of financial stringency. (MSE)

  16. Labour Market Flexibility: Trends in Enterprises.

    Science.gov (United States)

    Organisation for Economic Cooperation and Development, Paris (France).

    Since the mid-1980s, the Organisation for Economic Cooperation and Development (OECD) has carried out a number of studies on the issues of labor market flexibility under the supervision of the Manpower and Social Affairs Committee and its Working Party on Industrial Relations. While much of the previous work focused on the external forms of labor…

  17. Flexible Adaptivity in AEHS Using Policies

    NARCIS (Netherlands)

    Koesling, Arne; Krause, Daniel; Herder, Eelco

    2008-01-01

    Koesling, A., Krause, D., & Herder, E. (2008). Flexible Adaptivity in AEHS Using Policies. In W. Nejdl, J. Kay, P. Pu & E. Herder (Eds.), Proceedings Adaptive Hypermedia and Adaptive Web-Based Systems 5th International Conference, AH 2008 (pp. 410-415). July 29-August, 1, 2008, Hannover, Germany:

  18. Flexibility and a Departmental Instructional Planning Model.

    Science.gov (United States)

    Miner, Norris

    The flexibility of an educational program, institution, or system can be described as the ability of the unit to absorb negative responses, such as reductions in funding or enrollments, and continue to function in a viable manner. One approach to adjustment to such reductions is to effect cuts in personnel, current, and equipment spending. This…

  19. Higher Education--The Flexible Employment Sector?

    Science.gov (United States)

    Scott, Jill; Ridgley, Clare; Spurgeon, Peter

    2003-01-01

    Explored the extent to which policies and practices promoting work-life balance (family friendly policies) have been taken up within the English higher education sector. Responses from 50 higher education institutions show that flexible working practices are more widespread than the formal policies of institutions would suggest. (SLD)

  20. Productivity and employee satisfaction in flexible workplaces

    NARCIS (Netherlands)

    van der Voordt, Theo

    2004-01-01

    In the early 1990s, a few organisations in the Netherlands began to experiment with flexible workplaces. Traditional cellular offices and the open‐plan offices or team‐oriented bullpen spaces in which everyone had their own fixed workplace were no longer a matter of course. Making use of modern

  1. 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.

  2. Mechanical properties of flexible knitted composites

    NARCIS (Netherlands)

    Haan, de J.; Peijs, A.A.J.M.

    1996-01-01

    This study investigates the influence of the matrix material and the degree of prestretch of a knitted fibre structure on the mechanical properties of knitted composites with low fibre volume fractions. By embedding a flexible textile structure in an elastomeric matrix, composite materials are

  3. Unsedated Flexible Upper Gastrointestinal Endoscopy: Need for ...

    African Journals Online (AJOL)

    Background: To determine the incidence of oxygen desaturation and whether routine oxygen monitoring is necessary during unsedated diagnostic flexible upper gastrointestinal endoscopy. Methods: A prospective study involving 54 consecutive in and out patients who had diagnostic upper gastrointestinal endoscopy at ...

  4. Flexible spin-orbit torque devices

    International Nuclear Information System (INIS)

    Lee, OukJae; You, Long; Jang, Jaewon; Subramanian, Vivek; Salahuddin, Sayeef

    2015-01-01

    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 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

  5. 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.

  6. Making Professional Development Flexible: A Case Study.

    Science.gov (United States)

    Forsyth, Rachel

    2002-01-01

    Presents a case study of an online course that was designed for staff professional development at Manchester Metropolitan University (United Kingdom). Discusses the flexibility of online courses; course design; activities for short online workshops; evaluation methods for course evaluation; and results of participant questionnaires. (LRW)

  7. The Modelling of Axially Translating Flexible Beams

    Science.gov (United States)

    Theodore, R. J.; Arakeri, J. H.; Ghosal, A.

    1996-04-01

    The axially translating flexible beam with a prismatic joint can be modelled by using the Euler-Bernoulli beam equation together with the convective terms. In general, the method of separation of variables cannot be applied to solve this partial differential equation. In this paper, a non-dimensional form of the Euler Bernoulli beam equation is presented, obtained by using the concept of group velocity, and also the conditions under which separation of variables and assumed modes method can be used. The use of clamped-mass boundary conditions leads to a time-dependent frequency equation for the translating flexible beam. A novel method is presented for solving this time dependent frequency equation by using a differential form of the frequency equation. The assume mode/Lagrangian formulation of dynamics is employed to derive closed form equations of motion. It is shown by using Lyapunov's first method that the dynamic responses of flexural modal variables become unstable during retraction of the flexible beam, which the dynamic response during extension of the beam is stable. Numerical simulation results are presented for the uniform axial motion induced transverse vibration for a typical flexible beam.

  8. Functional flexibility good for skills development

    NARCIS (Netherlands)

    Houtman, I.L.D.

    2004-01-01

    Functional flexibility, making optimal use of the employee’s capacity to perform different tasks, is positively related to skills development and involvement in decision-making. It may lead to emotional exhaustion, however, if an imbalance exists, such as high job demands combined with a lack of

  9. 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...

  10. Can counter-stereotypes boost flexible thinking?

    NARCIS (Netherlands)

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

    2013-01-01

    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

  11. Biomass and biogas : potentials, efficiencies and flexibility

    NARCIS (Netherlands)

    Hofstede, Gert; Wouterse, Brian; Faber, Folkert; Nap, Jan Peter

    2012-01-01

    In the field of ‘renewable energy resources’ formation of biogas Biomass and biogas: potentials, efficiencies and flexibility is an important option. Biogas can be produced from biomass in a multistep process called anaerobic digestion (AD) and is usually performed in large digesters. Anaerobic

  12. 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...

  13. Flexible work and immigration in Europe

    NARCIS (Netherlands)

    Raess, D.; Burgoon, B.

    2015-01-01

    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

  14. Parametric Analysis of Flexible Logic Control Model

    Directory of Open Access Journals (Sweden)

    Lihua Fu

    2013-01-01

    Full Text Available Based on deep analysis about the essential relation between two input variables of normal two-dimensional fuzzy controller, we used universal combinatorial operation model to describe the logic relationship and gave a flexible logic control method to realize the effective control for complex system. In practical control application, how to determine the general correlation coefficient of flexible logic control model is a problem for further studies. First, the conventional universal combinatorial operation model has been limited in the interval [0,1]. Consequently, this paper studies a kind of universal combinatorial operation model based on the interval [a,b]. And some important theorems are given and proved, which provide a foundation for the flexible logic control method. For dealing reasonably with the complex relations of every factor in complex system, a kind of universal combinatorial operation model with unequal weights is put forward. Then, this paper has carried out the parametric analysis of flexible logic control model. And some research results have been given, which have important directive to determine the values of the general correlation coefficients in practical control application.

  15. Relative Effects of Psychological Flexibility, Parental Involvement ...

    African Journals Online (AJOL)

    A critical analysis and understanding of secondary students' experiences and of safety in public schools are currently lacking in the literature and warrant further research. This study investigated the relative effects of psychological flexibility, parental involvement and school climate on secondary school student's school ...

  16. Flexible thin-film NFC tags

    NARCIS (Netherlands)

    Myny, K.; Tripathi, A.K.; Steen, J.L. van der; Cobb, B.

    2015-01-01

    Thin-film transistor technologies have great potential to become the key technology for leafnode Internet of Things by utilizing the NFC protocol as a communication medium. The main requirements are manufacturability on flexible substrates at a low cost while maintaining good device performance

  17. Experience With Flexible Hours of Work

    Science.gov (United States)

    Hartley, Jo

    1976-01-01

    A summary of an 80-page booklet called Hours of Work When Workers Can Choose is presented. The booklet reports a survey and focuses on the benefits of flexible hours of work. It was published by the Business and Professional Women's Foundation and is available from that organization. (EC)

  18. Printable Transparent Conductive Films for Flexible Electronics.

    Science.gov (United States)

    Li, Dongdong; Lai, Wen-Yong; Zhang, Yi-Zhou; Huang, Wei

    2018-03-01

    Printed electronics are an important enabling technology for the development of low-cost, large-area, and flexible optoelectronic devices. Transparent conductive films (TCFs) made from solution-processable transparent conductive materials, such as metal nanoparticles/nanowires, carbon nanotubes, graphene, and conductive polymers, can simultaneously exhibit high mechanical flexibility, low cost, and better photoelectric properties compared to the commonly used sputtered indium-tin-oxide-based TCFs, and are thus receiving great attention. This Review summarizes recent advances of large-area flexible TCFs enabled by several roll-to-roll-compatible printed techniques including inkjet printing, screen printing, offset printing, and gravure printing using the emerging transparent conductive materials. The preparation of TCFs including ink formulation, substrate treatment, patterning, and postprocessing, and their potential applications in solar cells, organic light-emitting diodes, and touch panels are discussed in detail. The rational combination of a variety of printed techniques with emerging transparent conductive materials is believed to extend the opportunities for the development of printed electronics within the realm of flexible electronics and beyond. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. 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...

  20. Flexible Processes in Project-Centred Learning

    NARCIS (Netherlands)

    Ceri, Stefano; Matera, Maristella; Raffio, Alessandro; Spoelstra, Howard

    2007-01-01

    Ceri, S., Matera, M., Raffio, A. & Spoelstra, H. (2007). Flexible Processes in Project-Centred Learning. In E. Duval, R. Klamma, and M. Wolpers (Eds.), European Conference on Technology Enhanced Learning, Lecture Notes in Computer Science, Vol. 4753, pp. 463-468. Berlin Heidelberg: Springer-Verlag

  1. Will Flexible Learning Raise Student Achievement?

    Science.gov (United States)

    Guest, Ross

    2005-01-01

    This paper presents both theoretical and survey evidence on the effect of flexible learning--in particular, the shift to a more student-centred approach to learning--on academic achievement by students. A survey was conducted of 577 business students at a major Australian university in order to elicit their preferences for academic achievement and…

  2. 76 FR 40208 - Regulatory Flexibility Agenda

    Science.gov (United States)

    2011-07-07

    ...: Yes. Agency Contact: Alicia Goldin, Division of Trading and Markets, Securities and Exchange... Analysis Required: Yes. Agency Contact: Alicia Goldin, Division of Trading and Markets, Securities and... Flexibility Analysis Required: Yes. Agency Contact: Alicia Goldin, Division of Trading and Markets, Securities...

  3. Revealing the mechanisms of protein disorder and N-glycosylation in CD44-hyaluronan binding using molecular simulation

    Directory of Open Access Journals (Sweden)

    Olgun eGuvench

    2015-06-01

    Full Text Available The extracellular N-terminal hyaluronan binding domain (HABD of CD44 is a small globular domain that confers hyaluronan (HA binding functionality to this large transmembrane glycoprotein. When recombinantly expressed by itself, HABD exists as a globular water-soluble protein that retains the capacity to bind HA. This has enabled atomic-resolution structural biology experiments that have revealed the structure of HABD and its binding mode with oligomeric HA. Such experiments have also pointed to an order-to-disorder transition in HABD that is associated with HA binding. However, it had remained unclear how this structural transition was involved in binding since it occurs in a region of HABD distant from the HA-binding site. Furthermore, HABD is known to be N-glycosylated, and such glycosylation can diminish HA binding when the associated N-glycans are capped with sialic acid residues. The intrinsic flexibility of disordered proteins and of N-glycans makes it difficult to apply experimental structural biology approaches to probe the molecular mechanisms of how the order-to-disorder transition and N-glycosylation can modulate HA binding by HABD. We review recent results from molecular dynamics simulations that provide atomic-resolution mechanistic understanding of such modulation to help bridge gaps between existing experimental binding and structural biology data. Findings from these simulations include: Tyr42 may function as a molecular switch that converts the HA binding site from a low affinity to a high affinity state; in the partially-disordered form of HABD, basic amino acids in the C-terminal region can gain sufficient mobility to form direct contacts with bound HA to further stabilize binding; and terminal sialic acids on covalently-attached N-glycans can form charge-paired hydrogen bonding interactions with basic amino acids that could otherwise bind to HA, thereby blocking HA binding to glycosylated CD44 HABD.

  4. Production Flexibility in Extensive Beef Farming Systems

    Directory of Open Access Journals (Sweden)

    Laura Astigarraga

    2011-03-01

    Full Text Available The aim of this work is to assess the flexibility of production allowed by extensive production conditions faced with variations in the environment, i.e., market variations and climatic fluctuations, of Limousin beef systems. The study used a case-based methodology in which seven beef farms with less than 1 LU/ha were chosen. Data collection was based on three interviews using a semistructured questionnaire and on the analysis of productive and economic results over a 15-year period (1991-2005. The main evolution of these farms is related to a rise in work productivity associated with an increase in herd size. Herd increase was made possible by enlarging the area, the margin of intensification being limited in these regions. To take advantage of the enlarged land area, females were reared for fattening or for reproduction instead of selling them at weaning. The Limousin female provides a wide product mix because of its plasticity, as has been studied by several researchers. This mix flexibility is achieved by delaying product differentiation, a form of production flexibility that can reduce the risk of under-producing or over-producing varied product configurations. On the other hand, calves sold to the Italian market after weaning are generic products, associated with a flexible production process to overcome fluctuations in forage availability due to climatic variations. The introduction of maize silage for feeding acts as an alternative route, actual and potential, through the system to overcome unexpected forage shortage from natural grasslands as a result of droughts. The study shows that extensive farming systems have developed types of flexibility to match different factors of uncertainty from the environment. Finally, the issue of farm system performance is thus not so much a question of whether a farm is fit at a specific moment in time, but whether it transforms into a less or more sustainable orientation.

  5. Towards automated visual flexible endoscope navigation.

    Science.gov (United States)

    van der Stap, Nanda; van der Heijden, Ferdinand; Broeders, Ivo A M J

    2013-10-01

    The design of flexible endoscopes has not changed significantly in the past 50 years. A trend is observed towards a wider application of flexible endoscopes with an increasing role in complex intraluminal therapeutic procedures. The nonintuitive and nonergonomical steering mechanism now forms a barrier in the extension of flexible endoscope applications. Automating the navigation of endoscopes could be a solution for this problem. This paper summarizes the current state of the art in image-based navigation algorithms. The objectives are to find the most promising navigation system(s) to date and to indicate fields for further research. A systematic literature search was performed using three general search terms in two medical-technological literature databases. Papers were included according to the inclusion criteria. A total of 135 papers were analyzed. Ultimately, 26 were included. Navigation often is based on visual information, which means steering the endoscope using the images that the endoscope produces. Two main techniques are described: lumen centralization and visual odometry. Although the research results are promising, no successful, commercially available automated flexible endoscopy system exists to date. Automated systems that employ conventional flexible endoscopes show the most promising prospects in terms of cost and applicability. To produce such a system, the research focus should lie on finding low-cost mechatronics and technologically robust steering algorithms. Additional functionality and increased efficiency can be obtained through software development. The first priority is to find real-time, robust steering algorithms. These algorithms need to handle bubbles, motion blur, and other image artifacts without disrupting the steering process.

  6. Binding energies of cluster ions

    International Nuclear Information System (INIS)

    Parajuli, R.; Matt, S.; Scheier, P.; Echt, O.; Stamatovic, A.; Maerk, T.D.

    2002-01-01

    The binding energy of charged clusters may be measured by analyzing the kinetic energy released in the metastable decay of mass selected parent ions. Using finite heat bath theory to determine the binding energies of argon, neon, krypton, oxygen and nitrogen from their respective average kinetic energy released were carried out. A high-resolution double focussing two-sector mass spectrometer of reversed Nier-Johnson type geometry was used. MIKE ( mass-analysed ion kinetic energy) were measured to investigate decay reactions of mass-selected ions. For the inert gases neon (Ne n + ), argon (Ar n + ) and krypton (Kr n + ), it is found that the binding energies initially decrease with increasing size n and then level off at a value above the enthalpy of vaporization of the condensed phase. Oxygen cluster ions shown a characteristic dependence on cluster size (U-shape) indicating a change in the metastable fragmentation mechanism when going from the dimer to the decamer ion. (nevyjel)

  7. Metal binding by food components

    DEFF Research Database (Denmark)

    Tang, Ning

    for zinc binding by the investigated amino acids, peptides and proteins. The thiol group or imidazole group containing amino acids, peptides and proteins which exhibited strong zinc binding ability were further selected for interacting with zinc salts in relation to zinc absorption. The interactions...... between the above selected food components and zinc citrate or zinc phytate will lead to the enhanced solubility of zinc citrate or zinc phytate. The main driving force for this observed solubility enhancement is the complex formation between zinc and investigated food components as revealed by isothermal...... titration calorimetry and quantum mechanical calculations. This is due to the zinc binding affinity of the relatively softer ligands (investigated food components) will become much stronger than citrate or phytate when they present together in aqueous solution. This mechanism indicates these food components...

  8. The glycocalyx promotes cooperative binding and clustering of adhesion receptors.

    Science.gov (United States)

    Xu, Guang-Kui; Qian, Jin; Hu, Jinglei

    2016-05-18

    Cell adhesion plays a pivotal role in various biological processes, e.g., immune responses, cancer metastasis, and stem cell differentiation. The adhesion behaviors depend subtly on the binding kinetics of receptors and ligands restricted at the cell-substrate interfaces. Although much effort has been directed toward investigating the kinetics of adhesion molecules, the role of the glycocalyx, anchored on cell surfaces as an exterior layer, is still unclear. In this paper, we propose a theoretical approach to study the collective binding kinetics of a few and a large number of binders in the presence of the glycocalyx, representing the cases of initial and mature adhesions of cells, respectively. The analytical results are validated by finding good agreement with our Monte Carlo simulations. In the force loading case, the on-rate and affinity increase as more bonds form, whereas this cooperative effect is not observed in the displacement loading case. The increased thickness and stiffness of the glycocalyx tend to decrease the affinity for a few bonds, while they have less influence on the affinity for a large number of bonds. Moreover, for a flexible membrane with thermally-excited shape fluctuations, the glycocalyx is exhibited to promote the formation of bond clusters, mainly due to the cooperative binding of binders. This study helps to understand the cooperative kinetics of adhesion receptors under physiologically relevant loading conditions and sheds light on the novel role of the glycocalyx in cell adhesion.

  9. Skyrmions with low binding energies

    Energy Technology Data Exchange (ETDEWEB)

    Gillard, Mike, E-mail: m.n.gillard@leeds.ac.uk; Harland, Derek, E-mail: d.g.harland@leeds.ac.uk; Speight, Martin, E-mail: speight@maths.leeds.ac.uk

    2015-06-15

    Nuclear binding energies are investigated in two variants of the Skyrme model: the first replaces the usual Skyrme term with a term that is sixth order in derivatives, and the second includes a potential that is quartic in the pion fields. Solitons in the first model are shown to deviate significantly from ansätze previously assumed in the literature. The binding energies obtained in both models are lower than those obtained from the standard Skyrme model, and those obtained in the second model are close to the experimental values.

  10. Skyrmions with low binding energies

    International Nuclear Information System (INIS)

    Gillard, Mike; Harland, Derek; Speight, Martin

    2015-01-01

    Nuclear binding energies are investigated in two variants of the Skyrme model: the first replaces the usual Skyrme term with a term that is sixth order in derivatives, and the second includes a potential that is quartic in the pion fields. Solitons in the first model are shown to deviate significantly from ansätze previously assumed in the literature. The binding energies obtained in both models are lower than those obtained from the standard Skyrme model, and those obtained in the second model are close to the experimental values

  11. Skyrmions with low binding energies

    Directory of Open Access Journals (Sweden)

    Mike Gillard

    2015-06-01

    Full Text Available Nuclear binding energies are investigated in two variants of the Skyrme model: the first replaces the usual Skyrme term with a term that is sixth order in derivatives, and the second includes a potential that is quartic in the pion fields. Solitons in the first model are shown to deviate significantly from ansätze previously assumed in the literature. The binding energies obtained in both models are lower than those obtained from the standard Skyrme model, and those obtained in the second model are close to the experimental values.

  12. 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.

  13. Monte Carlo simulations of flexible polyanions complexing with whey proteins at their isoelectric point.

    Science.gov (United States)

    de Vries, R

    2004-02-15

    Electrostatic complexation of flexible polyanions with the whey proteins alpha-lactalbumin and beta-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-Huckel 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 alpha-lactalbumin complexes much more strongly than beta-lactoglobulin. For alpha-lactalbumin, strong complexation is due to localized binding to a single large positive "charge patch," whereas for beta-lactoglobulin, weak complexation is due to diffuse binding to multiple smaller charge patches. Copyright 2004 American Institute of Physics

  14. 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.

  15. Polyaniline modified flexible conducting paper for cancer detection

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Saurabh; Sen, Anindita; Kumar, Suveen; Augustine, Shine; Malhotra, Bansi D., E-mail: bansi.malhotra@gmail.com [Nanobioelectronics Laboratory, Department of Biotechnology, Delhi Technological University, Shahbad Daulatpur, Delhi 110042 (India); Yadav, Birendra K. [Rajiv Gandhi Cancer Institute and Research Centre, Rohini, Delhi 110085 (India); Mishra, Sandeep [Department of Applied Physics, Delhi Technological University, Shahbad Daulatpur, Delhi 110042 (India)

    2016-05-16

    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{sup −1} ml cm{sup 2}, shelf life of 22 days, and can be used to estimate CEA in the range of 2–20 ng ml{sup −1}. This paper sensor has been validated by detection of CEA in serum samples of cancer patients via immunoassay technique.

  16. Exploring the potential of a structural alphabet-based tool for mining multiple target conformations and target flexibility insight.

    Science.gov (United States)

    Regad, Leslie; Chéron, Jean-Baptiste; Triki, Dhoha; Senac, Caroline; Flatters, Delphine; Camproux, Anne-Claude

    2017-01-01

    Protein flexibility is often implied in binding with different partners and is essential for protein function. The growing number of macromolecular structures in the Protein Data Bank entries and their redundancy has become a major source of structural knowledge of the protein universe. The analysis of structural variability through available redundant structures of a target, called multiple target conformations (MTC), obtained using experimental or modeling methods and under different biological conditions or different sources is one way to explore protein flexibility. This analysis is essential to improve the understanding of various mechanisms associated with protein target function and flexibility. In this study, we explored structural variability of three biological targets by analyzing different MTC sets associated with these targets. To facilitate the study of these MTC sets, we have developed an efficient tool, SA-conf, dedicated to capturing and linking the amino acid and local structure variability and analyzing the target structural variability space. The advantage of SA-conf is that it could be applied to divers sets composed of MTCs available in the PDB obtained using NMR and crystallography or homology models. This tool could also be applied to analyze MTC sets obtained by dynamics approaches. Our results showed that SA-conf tool is effective to quantify the structural variability of a MTC set and to localize the structural variable positions and regions of the target. By selecting adapted MTC subsets and comparing their variability detected by SA-conf, we highlighted different sources of target flexibility such as induced by binding partner, by mutation and intrinsic flexibility. Our results support the interest to mine available structures associated with a target using to offer valuable insight into target flexibility and interaction mechanisms. The SA-conf executable script, with a set of pre-compiled binaries are available at http://www.mti.univ-paris-diderot.fr/recherche/plateformes/logiciels.

  17. Exploring the potential of a structural alphabet-based tool for mining multiple target conformations and target flexibility insight.

    Directory of Open Access Journals (Sweden)

    Leslie Regad

    Full Text Available Protein flexibility is often implied in binding with different partners and is essential for protein function. The growing number of macromolecular structures in the Protein Data Bank entries and their redundancy has become a major source of structural knowledge of the protein universe. The analysis of structural variability through available redundant structures of a target, called multiple target conformations (MTC, obtained using experimental or modeling methods and under different biological conditions or different sources is one way to explore protein flexibility. This analysis is essential to improve the understanding of various mechanisms associated with protein target function and flexibility. In this study, we explored structural variability of three biological targets by analyzing different MTC sets associated with these targets. To facilitate the study of these MTC sets, we have developed an efficient tool, SA-conf, dedicated to capturing and linking the amino acid and local structure variability and analyzing the target structural variability space. The advantage of SA-conf is that it could be applied to divers sets composed of MTCs available in the PDB obtained using NMR and crystallography or homology models. This tool could also be applied to analyze MTC sets obtained by dynamics approaches. Our results showed that SA-conf tool is effective to quantify the structural variability of a MTC set and to localize the structural variable positions and regions of the target. By selecting adapted MTC subsets and comparing their variability detected by SA-conf, we highlighted different sources of target flexibility such as induced by binding partner, by mutation and intrinsic flexibility. Our results support the interest to mine available structures associated with a target using to offer valuable insight into target flexibility and interaction mechanisms. The SA-conf executable script, with a set of pre-compiled binaries are available at

  18. Three-dimensional formulation of rigid-flexible multibody systems with flexible beam elements

    International Nuclear Information System (INIS)

    Garcia-Vallejo, D.; Mayo, J.; Escalona, J. L.; Dominguez, J.

    2008-01-01

    Multibody systems generally contain solids with appreciable deformations and which decisively influence the dynamics of the system. These solids have to be modeled by means of special formulations for flexible solids. At the same time, other solids are of such a high stiffness that they may be considered rigid, which simplifies their modeling. For these reasons, for a rigid-flexible multibody system, two types of formulations coexist in the equations of the system. Among the different possibilities provided in the literature on the material, the formulation in natural coordinates and the formulation in absolute nodal coordinates are utilized in this paper to model the rigid and flexible solids, respectively. This paper contains a mixed formulation based on the possibility of sharing coordinates between a rigid solid and a flexible solid. The global mass matrix of the system is shown to be constant and, in addition, many of the constraint equations obtained upon utilizing these formulations are linear and can be eliminated

  19. Optimized flexible cover films for improved conversion efficiency in thin film flexible solar cells

    Science.gov (United States)

    Guterman, Sidney; Wen, Xin; Gudavalli, Ganesh; Rhajbhandari, Pravakar; Dhakal, Tara P.; Wilt, David; Klotzkin, David

    2018-05-01

    Thin film solar cell technologies are being developed for lower cost and flexible applications. For such technologies, it is desirable to have inexpensive, flexible cover strips. In this paper, we demonstrate that transparent silicone cover glass adhesive can be doped with TiO2 nanoparticles to achieve an optimal refractive index and maximize the performance of the cell. Cells covered with the film doped with nanoparticles at the optimal concentration demonstrated a ∼1% increase in photocurrent over the plain (undoped) film. In addition, fused silica beads can be incorporated into the flexible cover slip to realize a built-in pseudomorphic glass diffuser layer as well. This additional degree of freedom in engineering flexible solar cell covers allows maximal performance from a given cell for minimal increased cost.

  20. Considerations of device and operational flexibility in FER

    International Nuclear Information System (INIS)

    Sugihara, Masayoshi; Miki, Nobuharu; Nishio, Satoshi; Yamada, Masao; Yamamoto, Shin

    1988-01-01

    Expected physics uncertainties in DT burning plasma of FER, which may not be removed completely at the start of construction or DT operation, are reviewed. Several possible device and operational flexibility scenarios to cope with these uncertainties are considered. They are (1) Plasma size enlargement scenario, (2) Plasma shape flexibility scenario, (3) Heating/Current drive/Control system flexibility scenario, (4) Impurity control system flexibility scenario and (5) Advanced operation scenario. Feasibility of these flexibility scenarios are examined and shown to be practicable. However, careful assessment of the physics data base is necessary at the start of construction and DT operation to proceed to actually implement these flexibilities in FER. (author)

  1. Subnanomolar Inhibitor of Cytochrome bc1 Complex Designed via Optimizing Interaction with Conformationally Flexible Residues

    Science.gov (United States)

    Zhao, Pei-Liang; Wang, Le; Zhu, Xiao-Lei; Huang, Xiaoqin; Zhan, Chang-Guo; Wu, Jia-Wei; Yang, Guang-Fu

    2009-01-01

    Cytochrome bc1 complex (EC 1.10.2.2, bc1), an essential component of the cellular respiratory chain and the photosynthetic apparatus in photosynthetic bacteria, has been identified as a promising target for new drugs and agricultural fungicides. X-ray diffraction structures of the free bc1 complex and its complexes with various inhibitors revealed that the phenyl group of Phe274 in the binding pocket exhibited significant conformational flexibility upon different inhibitors binding to optimize respective π-π interactions, whereas the side chains of other hydrophobic residues showed conformational stability. Therefore, in the present study, a strategy of optimizing the π-π interaction with conformationally flexible residues was proposed to design and discover new bc1 inhibitors with a higher potency. Eight new compounds were designed and synthesized, among which compound 5c with a Ki value of 570 pM was identified as the most promising drug or fungicide candidate, significantly more potent than the commercially available bc1 inhibitors including azoxystrobin (AZ), kresoxim-methyl (KM), and pyraclostrobin (PY). To our knowledge, this is the first bc1 inhibitor discovered from structure-based design with a potency of subnanomolar Ki value. For all of the compounds synthesized and assayed, the calculated binding free energies correlated reasonably well with the binding free energies derived from the experimental Ki values with a correlation coefficient of r2 = 0.89. The further inhibitory kinetics studies revealed that compound 5c is a non-competitive inhibitor with respect to substrate cytochrome c, but is a competitive inhibitor with respect to substrate ubiquinol. Due to its subnanomolar Ki potency and slow dissociation rate constant (k−0 = 0.00358 s−1), compound 5c could be used as a specific probe for further elucidation of the mechanism of bc1 function and as a new lead compound for future drug discovery. PMID:19928849

  2. [Inspecting the cochlear scala tympanic with flexible and semi-flexible micro-endoscope].

    Science.gov (United States)

    Zhang, Daoxcing; Zhang, Yankun

    2006-02-01

    Flexible and semi-flexible micro-endoscopes were used in cochlear scala tympani inspection , to explore their application in inner ear examination. Fifteen profound hearing loss patients preparing for cochlear implant were included in this study. During the operation, micro-endoscopy was performed after opening the cochlear scala tympani. And 1 mm diameter semi-flexible micro-endoscope could go as deep as 9 mm into the cochlear scala tympani, while 0. 5 mm diameter flexible micro-endoscope could go as deep as 25 mm. The inspecting results were compared with video recording. Using 0.5 mm flexible micro-endoscope, we canould check cochlear scala tympani with depth range of 15-25 mm, but the video imaging was not clear enough to examine the microstructure in the cochlear. With 1 mm diameter semi-flexible micro-endoscope, we could reach 9 mm deep into the cochlear. During the examination, we found 3 cases with calcification deposit in osseous spiral lamina, l case with granulation tissue in the lateral wall of scala tympani, no abnormal findings in the other 11 cases. Inspecting the cochlear scala tympani with 0.5 mm flexible micro-endoscope, even though we can reach the second circuit of the cochlear, it is difficult to find the pathology in the cochlear because of the poor video imaging. With 1 mm semi-flexible micro-endoscope, we can identify the microstructure of the cochlear clearly and find the pathologic changes, but the inserting depth was limited to 9 mm with limitation to examine the whole cochlear.

  3. Flexible MEMS: A novel technology to fabricate flexible sensors and electronics

    Science.gov (United States)

    Tu, Hongen

    This dissertation presents the design and fabrication techniques used to fabricate flexible MEMS (Micro Electro Mechanical Systems) devices. MEMS devices and CMOS(Complementary Metal-Oxide-Semiconductor) circuits are traditionally fabricated on rigid substrates with inorganic semiconductor materials such as Silicon. However, it is highly desirable that functional elements like sensors, actuators or micro fluidic components to be fabricated on flexible substrates for a wide variety of applications. Due to the fact that flexible substrate is temperature sensitive, typically only low temperature materials, such as polymers, metals, and organic semiconductor materials, can be directly fabricated on flexible substrates. A novel technology based on XeF2(xenon difluoride) isotropic silicon etching and parylene conformal coating, which is able to monolithically incorporate high temperature materials and fluidic channels, was developed at Wayne State University. The technology was first implemented in the development of out-of-plane parylene microneedle arrays that can be individually addressed by integrated flexible micro-channels. These devices enable the delivery of chemicals with controlled temporal and spatial patterns and allow us to study neurotransmitter-based retinal prosthesis. The technology was further explored by adopting the conventional SOI-CMOS processes. High performance and high density CMOS circuits can be first fabricated on SOI wafers, and then be integrated into flexible substrates. Flexible p-channel MOSFETs (Metal-Oxide-Semiconductor Field-Effect-Transistors) were successfully integrated and tested. Integration of pressure sensors and flow sensors based on single crystal silicon has also been demonstrated. A novel smart yarn technology that enables the invisible integration of sensors and electronics into fabrics has been developed. The most significant advantage of this technology is its post-MEMS and post-CMOS compatibility. Various high

  4. Cellulose binding domain fusion proteins

    Science.gov (United States)

    Shoseyov, Oded; Shpiegl, Itai; Goldstein, Marc A.; Doi, Roy H.

    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.

  5. When is protein binding important?

    Science.gov (United States)

    Heuberger, Jules; Schmidt, Stephan; Derendorf, Hartmut

    2013-09-01

    The present paper is an ode to a classic citation by Benet and Hoener (2002. Clin Pharm Ther 71(3):115-121). The now classic paper had a huge impact on drug development and the way the issue of protein binding is perceived and interpreted. Although the authors very clearly pointed out the limitations and underlying assumptions for their delineations, these are too often overlooked and the classic paper's message is misinterpreted by broadening to cases that were not intended. Some members of the scientific community concluded from the paper that protein binding is not important. This was clearly not intended by the authors, as they finished their paper with a paragraph entitled: "When is protein binding important?" Misinterpretation of the underlying assumptions in the classic work can result in major pitfalls in drug development. Therefore, we revisit the topic of protein binding with the intention of clarifying when clinically relevant changes should be considered during drug development. Copyright © 2013 Wiley Periodicals, Inc.

  6. Structural consequences of cutting a binding loop: two circularly permuted variants of streptavidin

    International Nuclear Information System (INIS)

    Le Trong, Isolde; Chu, Vano; Xing, Yi; Lybrand, Terry P.; Stayton, Patrick S.; Stenkamp, Ronald E.

    2013-01-01

    The crystal structures of two circularly permuted streptavidins probe the role of a flexible loop in the tight binding of biotin. Molecular-dynamics calculations for one of the mutants suggests that increased fluctuations in a hydrogen bond between the protein and biotin are associated with cleavage of the binding loop. Circular permutation of streptavidin was carried out in order to investigate the role of a main-chain amide in stabilizing the high-affinity complex of the protein and biotin. Mutant proteins CP49/48 and CP50/49 were constructed to place new N-termini at residues 49 and 50 in a flexible loop involved in stabilizing the biotin complex. Crystal structures of the two mutants show that half of each loop closes over the binding site, as observed in wild-type streptavidin, while the other half adopts the open conformation found in the unliganded state. The structures are consistent with kinetic and thermodynamic data and indicate that the loop plays a role in enthalpic stabilization of the bound state via the Asn49 amide–biotin hydrogen bond. In wild-type streptavidin, the entropic penalties of immobilizing a flexible portion of the protein to enhance binding are kept to a manageable level by using a contiguous loop of medium length (six residues) which is already constrained by its anchorage to strands of the β-barrel protein. A molecular-dynamics simulation for CP50/49 shows that cleavage of the binding loop results in increased structural fluctuations for Ser45 and that these fluctuations destabilize the streptavidin–biotin complex

  7. In Silico Mechanistic Profiling to Probe Small Molecule Binding to Sulfotransferases

    Science.gov (United States)

    Martiny, Virginie Y.; Carbonell, Pablo; Lagorce, David; Villoutreix, Bruno O.; Moroy, Gautier; Miteva, Maria A.

    2013-01-01

    Drug metabolizing enzymes play a key role in the metabolism, elimination and detoxification of xenobiotics, drugs and endogenous molecules. While their principal role is to detoxify organisms by modifying compounds, such as pollutants or drugs, for a rapid excretion, in some cases they render their substrates more toxic thereby inducing severe side effects and adverse drug reactions, or their inhibition can lead to drug–drug interactions. We focus on sulfotransferases (SULTs), a family of phase II metabolizing enzymes, acting on a large number of drugs and hormones and showing important structural flexibility. Here we report a novel in silico structure-based approach to probe ligand binding to SULTs. We explored the flexibility of SULTs by molecular dynamics (MD) simulations in order to identify the most suitable multiple receptor conformations for ligand binding prediction. Then, we employed structure-based docking-scoring approach to predict ligand binding and finally we combined the predicted interaction energies by using a QSAR methodology. The results showed that our protocol successfully prioritizes potent binders for the studied here SULT1 isoforms, and give new insights on specific molecular mechanisms for diverse ligands’ binding related to their binding sites plasticity. Our best QSAR models, introducing predicted protein-ligand interaction energy by using docking, showed accuracy of 67.28%, 78.00% and 75.46%, for the isoforms SULT1A1, SULT1A3 and SULT1E1, respectively. To the best of our knowledge our protocol is the first in silico structure-based approach consisting of a protein-ligand interaction analysis at atomic level that considers both ligand and enzyme flexibility, along with a QSAR approach, to identify small molecules that can interact with II phase dug metabolizing enzymes. PMID:24039991

  8. In silico mechanistic profiling to probe small molecule binding to sulfotransferases.

    Directory of Open Access Journals (Sweden)

    Virginie Y Martiny

    Full Text Available Drug metabolizing enzymes play a key role in the metabolism, elimination and detoxification of xenobiotics, drugs and endogenous molecules. While their principal role is to detoxify organisms by modifying compounds, such as pollutants or drugs, for a rapid excretion, in some cases they render their substrates more toxic thereby inducing severe side effects and adverse drug reactions, or their inhibition can lead to drug-drug interactions. We focus on sulfotransferases (SULTs, a family of phase II metabolizing enzymes, acting on a large number of drugs and hormones and showing important structural flexibility. Here we report a novel in silico structure-based approach to probe ligand binding to SULTs. We explored the flexibility of SULTs by molecular dynamics (MD simulations in order to identify the most suitable multiple receptor conformations for ligand binding prediction. Then, we employed structure-based docking-scoring approach to predict ligand binding and finally we combined the predicted interaction energies by using a QSAR methodology. The results showed that our protocol successfully prioritizes potent binders for the studied here SULT1 isoforms, and give new insights on specific molecular mechanisms for diverse ligands' binding related to their binding sites plasticity. Our best QSAR models, introducing predicted protein-ligand interaction energy by using docking, showed accuracy of 67.28%, 78.00% and 75.46%, for the isoforms SULT1A1, SULT1A3 and SULT1E1, respectively. To the best of our knowledge our protocol is the first in silico structure-based approach consisting of a protein-ligand interaction analysis at atomic level that considers both ligand and enzyme flexibility, along with a QSAR approach, to identify small molecules that can interact with II phase dug metabolizing enzymes.

  9. Flexible Piezoelectric Sensor-Based Gait Recognition

    Directory of Open Access Journals (Sweden)

    Youngsu Cha

    2018-02-01

    Full Text Available Most motion recognition research has required tight-fitting suits for precise sensing. However, tight-suit systems have difficulty adapting to real applications, because people normally wear loose clothes. In this paper, we propose a gait recognition system with flexible piezoelectric sensors in loose clothing. The gait recognition system does not directly sense lower-body angles. It does, however, detect the transition between standing and walking. Specifically, we use the signals from the flexible sensors attached to the knee and hip parts on loose pants. We detect the periodic motion component using the discrete time Fourier series from the signal during walking. We adapt the gait detection method to a real-time patient motion and posture monitoring system. In the monitoring system, the gait recognition operates well. Finally, we test the gait recognition system with 10 subjects, for which the proposed system successfully detects walking with a success rate over 93 %.

  10. Flexible management: strategies for the changing workforce.

    Science.gov (United States)

    Michaels, B

    1994-01-01

    In the year 2000, managers will supervise employees whose career aspirations differ drastically from their own. Success not only will be measured by salary and status, but will be tied to a person's family relationships. Twenty years ago, most managers were not concerned with the family problems of their subordinates. This notion is now out of date. The family responsibilities of staff have a direct effect on the company's productivity. An employee who is worried about the care of an elderly parent, or concerned with the safety of a preteen home alone after school, is unlikely to give full attention to the task at hand. Flexible management is a cost-effective way of dealing with these issues. Managers who have the skills to be flexible and the strategies to work with employees for a win-win situation will reduce distractions and tardiness and gain productivity and loyalty.

  11. Industrial Mining's flexibility aids in customer satisfaction

    Energy Technology Data Exchange (ETDEWEB)

    1985-08-01

    Mining flexibility and customer specification keeps Industrial Mining of Youngstown, Ohio competitive in a tough environment. The company fills the needs of the small customer who requires a special blend or sized product. Industrial Mining works terrain that was uneconomical to mine before but is now profitable. Draglines and mobile equipment are used for overburden removal for economical and flexible mining with most mining by the contour method. Industrial Mining's preparation plant was constructed in 1979 to enable the company to wash and screen different stoker products and utility coal with a modern on-site lab a quality product can be constantly maintained. A wheel loader is used to feed the hopper from selective stockpiles and this allows blending on the raw side or within the plant.

  12. A screen-printed flexible flow sensor

    International Nuclear Information System (INIS)

    Moschos, A; Kaltsas, G; Syrovy, T; Syrova, L

    2017-01-01

    A thermal flow sensor was printed on a flexible plastic substrate using exclusively screen-printing techniques. The presented device was implemented with custom made screen-printed thermistors, which allows simple, cost-efficient production on a variety of flexible substrates while maintaining the typical advantages of thermal flow sensors. Evaluation was performed for both static (zero flow) and dynamic conditions using a combination of electrical measurements and IR imaging techniques in order to determine important characteristics, such as temperature response, output repeatability, etc. The flow sensor was characterized utilizing the hot-wire and calorimetric principles of operation, while the preliminary results appear to be very promising, since the sensor was successfully evaluated and displayed adequate sensitivity in a relatively wide flow range. (paper)

  13. Flexible work schedules, older workers, and retirement.

    Science.gov (United States)

    Siegenthaler, J K; Brenner, A M

    2000-01-01

    Older workers in the United States indicate that they would prefer flexible work arrangements rather than abrupt retirement, yet management has done very little to make this possible. A review of two bodies of literature from the late 1980s is presented: social science writings including sociological, gerontological, and economic literature, and business and management literature. There is a clash between the way jobs are traditionally scheduled and the needs of growing numbers of older workers. Workers continue to be subject to obstacles to phased retirement due to the structuring of health care and pension benefits, downsizing, organizational inflexibility, and "corporate culture." Thus, general views among social scientists regarding the desirability of flexible schedules toward retirement will not produce real changes unless management becomes committed to such changes and they are securely embedded in company policies.

  14. 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.

  15. 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...... constrained behavior can be modeled and used by a defrost planner to optimally schedule defrost start times for several defrost cycles, according to electricity price. Because the defrost planning problem is a boolean programming problem a method of relaxing it is proposed. While the relaxed problem requires...... less computational effort, convexity is dependent on properties of the price signal. Simulation study show that the optimal planning strategy can reduce cost of defrost cycles with 31.7%, compared to a current strategy of executing all defrost cycles at the same time each day. Copyright ©2015 by IEEE...

  16. Flexible Software Process Lines in Practice

    DEFF Research Database (Denmark)

    Kuhrmann, Marco; Ternité, Thomas; Friedrich, Jan

    2016-01-01

    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...... 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 XT and to allow for improved process variability and lifecycle management. Practical dissemination and complementing empirical research show the suitability of the concept. We therefore contribute a proven approach that is presented as metamodel fragment for reuse and implementation in further...

  17. Varying flexibilities in systems of organised decentralisation

    DEFF Research Database (Denmark)

    Ilsøe, Anna; Andersen, Søren Kaj

    to unbalanced trade offs. In Denmark the strong decentralisation combined with a lacking demand on +/- hours limits for time banks without reference periods seems to impose risks for certain groups of employees who, regardless of company size, can have extraordinary long working hours violating the 48-hour rule......There seems to be a paradox: The use of flexible working hours (i.e. variable hours) is more widespread in Germany than in Denmark, yet at the same time the discussion on the need for further flexibilisation of working hours is also more prevalent in Germany than in Denmark. In order to answer...... 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...

  18. Analysis of flexible structures under lateral impact

    International Nuclear Information System (INIS)

    Ramirez, D. F.; Razavi, H.

    2012-01-01

    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)

  19. Prediction of consensus binding mode geometries for related chemical series of positive allosteric modulators of adenosine and muscarinic acetylcholine receptors.

    Science.gov (United States)

    Sakkal, Leon A; Rajkowski, Kyle Z; Armen, Roger S

    2017-06-05

    Following insights from recent crystal structures of the muscarinic acetylcholine receptor, binding modes of Positive Allosteric Modulators (PAMs) were predicted under the assumption that PAMs should bind to the extracellular surface of the active state. A series of well-characterized PAMs for adenosine (A 1 R, A 2A R, A 3 R) and muscarinic acetylcholine (M 1 R, M 5 R) receptors were modeled using both rigid and flexible receptor CHARMM-based molecular docking. Studies of adenosine receptors investigated the molecular basis of the probe-dependence of PAM activity by modeling in complex with specific agonist radioligands. Consensus binding modes map common pharmacophore features of several chemical series to specific binding interactions. These models provide a rationalization of how PAM binding slows agonist radioligand dissociation kinetics. M 1 R PAMs were predicted to bind in the analogous M 2 R PAM LY2119620 binding site. The M 5 R NAM (ML-375) was predicted to bind in the PAM (ML-380) binding site with a unique induced-fit receptor conformation. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  20. Flexible Supercapacitors Based on Carbon Nanomaterials

    Science.gov (United States)

    2014-02-26

    spray-coated directly onto either exible nonconductive substrates (e.g., plastic lm, cellulose paper, and office paper) as both the current electrode...1D carbon nanotubes, 2D graphene, and 3D mesoporous carbon, are promising as electrode materials for flexible supercapacitors due to their extremely...H2SO4 gels) between positive/negative electrodes supported with exible plastic substrates (e.g., polydimethylsi- loxane, PDMS).34–36 Unlike