Sample records for binds flexible gc-rich

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

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


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

  2. Prevention of copper-induced cell death by GC-rich DNA oligomers in murine macrophage-like RAW264.7 cells. (United States)

    Matsushita, Sakiko; Mochizuki, Shinichi; Sakurai, Kazuo; Kawano, Tomonori


    Impact of redox active transition metals on activation of cell death signaling in plant cells have been documented to date. We have recently reported that GC-rich DNA oligomers with high affinity for binding of copper and catalytic activity for removal of ROS as novel plant cell-protecting agents. Here, we show that similar DNA oligomers protect the mouse macrophage-like RAW264.7 cells from copper-induced cell death, suggesting that the phenomenon firstly observed in plant model can be expanded to a wider range of cells and/or organisms including mammalian cells.

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

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    Daniel García-Souto


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

  4. Apoptotic lymphocytes of H. sapiens lose nucleosomes in GC-rich promoters. (United States)

    Hosid, Sergey; Ioshikhes, Ilya


    We analyzed two sets of human CD4+ nucleosomal DNA directly sequenced by Illumina (Solexa) high throughput sequencing method. The first set has ∼40 M sequences and was produced from the normal CD4+ T lymphocytes by micrococcal nuclease. The second set has ∼44 M sequences and was obtained from peripheral blood lymphocytes by apoptotic nucleases. The different nucleosome sets showed similar dinucleotide positioning AA/TT, GG/CC, and RR/YY (R is purine, Y--pyrimidine) patterns with periods of 10-10.4 bp. Peaks of GG/CC and AA/TT patterns were shifted by 5 bp from each other. Two types of promoters in H. sapiens: AT and GC-rich were identified. AT-rich promoters in apoptotic cell had +1 nucleosome shifts 50-60 bp downstream from those in normal lymphocytes. GC-rich promoters in apoptotic cells lost 80% of nucleosomes around transcription start sites as well as in total DNA. Nucleosome positioning was predicted by combination of {AA, TT}, {GG, CC}, {WW, SS} and {RR, YY} patterns. In our study we found that the combinations of {AA, TT} and {GG, CC} provide the best results and successfully mapped 33% of nucleosomes 147 bp long with precision ±15 bp (only 31/147 or 21% is expected).

  5. Vertebrate codon bias indicates a highly GC-rich ancestral genome. (United States)

    Nabiyouni, Maryam; Prakash, Ashwin; Fedorov, Alexei


    Two factors are thought to have contributed to the origin of codon usage bias in eukaryotes: 1) genome-wide mutational forces that shape overall GC-content and create context-dependent nucleotide bias, and 2) positive selection for codons that maximize efficient and accurate translation. Particularly in vertebrates, these two explanations contradict each other and cloud the origin of codon bias in the taxon. On the one hand, mutational forces fail to explain GC-richness (~60%) of third codon positions, given the GC-poor overall genomic composition among vertebrates (~40%). On the other hand, positive selection cannot easily explain strict regularities in codon preferences. Large-scale bioinformatic assessment, of nucleotide composition of coding and non-coding sequences in vertebrates and other taxa, suggests a simple possible resolution for this contradiction. Specifically, we propose that the last common vertebrate ancestor had a GC-rich genome (~65% GC). The data suggest that whole-genome mutational bias is the major driving force for generating codon bias. As the bias becomes prominent, it begins to affect translation and can result in positive selection for optimal codons. The positive selection can, in turn, significantly modulate codon preferences.

  6. 高GC含量DNA模板的PCR扩增%PCR Amplification of GC-Rich DNA

    Institute of Scientific and Technical Information of China (English)

    邢玉华; 戴素琴; 刘体颜; 王微; 谭俊杰; 曲国龙; 刘刚; 陈惠鹏


    目的::探索高GC含量DNA的PCR扩增条件,为扩增达托霉素生物合成基因簇及拼接奠定基础。方法:在PCR扩增体系中,使用高保真的聚合酶及添加不同浓度的DMSO、7-deaza-dGTP等增强剂,并选择合适的PCR循环程序,优化富含GC的DNA的PCR扩增条件。结果:向反应体系中额外添加1%~4%的DMSO可以显著提高富含GC的DNA的PCR扩增产物量,但会降低其特异性;7-deaza-dGTP可以提高扩增产物的特异性及保真度,但产量会有所下降。应用touch down PCR并在体系中添加7-deaza-dGTP能够提高扩增产物的特异性和产率,增加扩增的保真度。结论:应用优化的PCR扩增条件将所有达托霉素生物合成基因簇分段扩增出来,并可扩增出长达6 kb的片段,且序列完全正确,可以进行后续拼接。%Objective: To determine the optimized conditions for PCR amplification of DNA with rich GC in or-der to amplify DNA fragments from daptomycin biosynthetic gene cluster and further for assembly. Methods:DMSO and 7-deaza-dGTP were added to the PCR amplification system and amplification cycling was chosen to optimize the conditions for PCR amplification of DNA with rich GC. Results: 1%~4% DMSO greatly improved tar-get product yield during PCR amplification but the specificity was reduced. 7-deaza-dGTP improved target prod-uct specificity and facilitated subsequent sequencing of GC-rich DNA, although product yield was not increased. Combination touch down PCR with 7-deaza-dGTP had good effect on PCR amplification, and will allow for the production of a wide variety of GC-rich gene constructs. Conclusion: Using this protocol, all the 1 kb DNA frag-ments from daptomycin biosynthetic gene cluster were successfully amplified and long DNA fragments up to 6 kb were also amplified, which will facilitate our thorough understanding to genes and their regulations and functions.

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

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    Vladimir Pavan Margarido


    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. (United States)

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


    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.

  9. 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.


    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.

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

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    Anthony M Pedley

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

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

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


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

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

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


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

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

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    Susanne Liese


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

  14. Influence of length and flexibility of spacers on the binding affinity of divalent ligands. (United States)

    Liese, Susanne; Netz, Roland R


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

  15. Flexibility. (United States)

    Humphrey, L. Dennis


    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)

  16. In Pursuit of Fully Flexible Protein-Ligand Docking: Modeling the Bilateral Mechanism of Binding. (United States)

    Henzler, Angela M; Rarey, Matthias


    Modern structure-based drug design aims at accounting for the intrinsic flexibility of therapeutic relevant targets. Over the last few years a considerable amount of docking approaches that encounter this challenging problem has emerged. Here we provide the readership with an overview of established methods for fully flexible protein-ligand docking and current developments in the field. All methods are based on one of two fundamental models which describe the dynamic behavior of proteins upon ligand binding. Methods for ensemble docking (ED) model the protein conformational change before the ligand is placed, whereas induced-fit docking (IFD) optimizes the protein structure afterwards. A third category of docking approaches is formed by recent approaches that follow both concepts. This categorization allows to comprehensively discover strengths and weaknesses of the individual processes and to extract information for their applicability in real world docking scenarios.

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

    Indian Academy of Sciences (India)



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

  18. 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

  19. Structures of parasite calreticulins provide insights into their flexibility and dual carbohydrate/peptide-binding properties (United States)

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


    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. PMID:27840680

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

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    Changrui Lu

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

  1. Molecular dynamics studies of the nucleoprotein of influenza A virus: role of the protein flexibility in RNA binding.

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    Bogdan Tarus

    Full Text Available The influenza viruses contain a segmented, negative stranded RNA genome. Each RNA segment is covered by multiple copies of the nucleoprotein (NP. X-ray structures have shown that NP contains well-structured domains juxtaposed with regions of missing electron densities corresponding to loops. In this study, we tested if these flexible loops gated or promoted RNA binding and RNA-induced oligomerization of NP. We first performed molecular dynamics simulations of wt NP monomer and trimer in comparison with the R361A protein mutated in the RNA binding groove, using the H1N1 NP as the initial structure. Calculation of the root-mean-square fluctuations highlighted the presence of two flexible loops in NP trimer: loop 1 (73-90, loop 2 (200-214. In NP, loops 1 and 2 formed a 10-15 Å-wide pinch giving access to the RNA binding groove. Loop 1 was stabilized by interactions with K113 of the adjacent β-sheet 1 (91-112 that interacted with the RNA grove (linker 360-373 via multiple hydrophobic contacts. In R361A, a salt bridge formed between E80 of loop 1 and R208 of loop 2 driven by hydrophobic contacts between L79 and W207, due to a decreased flexibility of loop 2 and loop 1 unfolding. Thus, RNA could not access its binding groove in R361A; accordingly, R361A had a much lower affinity for RNA than NP. Disruption of the E80-R208 interaction in the triple mutant R361A-E80A-E81A increased its RNA binding affinity and restored its oligomerization back to wt levels in contrast with impaired levels of R361A. Our data suggest that the flexibility of loops 1 and 2 is required for RNA sampling and binding which likely involve conformational change(s of the nucleoprotein.

  2. Effects of Biomolecular Flexibility on Alchemical Calculations of Absolute Binding Free Energies. (United States)

    Lawrenz, Morgan; Baron, Riccardo; Wang, Yi; McCammon, J Andrew


    The independent trajectory thermodynamic integration (IT-TI) approach (Lawrenz et. al J. Chem. Theory. Comput. 2009, 5:1106-1116(1)) for free energy calculations with distributed computing is employed to study two distinct cases of protein-ligand binding: first, the influenza surface protein N1 neuraminidase bound to the inhibitor oseltamivir, and second, the M. tuberculosis enzyme RmlC complexed with the molecule CID 77074. For both systems, finite molecular dynamics (MD) sampling and varied molecular flexibility give rise to IT-TI free energy distributions that are remarkably centered on the target experimental values, with a spread directly related to protein, ligand, and solvent dynamics. Using over 2 μs of total MD simulation, alternative protocols for the practical, general implementation of IT-TI are investigated, including the optimal use of distributed computing, the total number of alchemical intermediates, and the procedure to perturb electrostatics and van der Waals interactions. A protocol that maximizes predictive power and computational efficiency is proposed. IT-TI outperforms traditional TI predictions and allows a straightforward evaluation of the reliability of free energy estimates. Our study has broad implications for the use of distributed computing in free energy calculations of macromolecular systems.

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

    DEFF Research Database (Denmark)

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


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

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


    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 IC50 values ⩽1μM and 11 effective at ⩽2μM in an ex vivo assay.

  5. Benzimidazole inhibitors of the protein kinase CHK2: Clarification of the binding mode by flexible side chain docking and protein–ligand crystallography (United States)

    Matijssen, Cornelis; Silva-Santisteban, M. Cris; Westwood, Isaac M.; Siddique, Samerene; Choi, Vanessa; Sheldrake, Peter; van Montfort, Rob L.M.; Blagg, Julian


    Two closely related binding modes have previously been proposed for the ATP-competitive benzimidazole class of checkpoint kinase 2 (CHK2) inhibitors; however, neither binding mode is entirely consistent with the reported SAR. Unconstrained rigid docking of benzimidazole ligands into representative CHK2 protein crystal structures reveals an alternative binding mode involving a water-mediated interaction with the hinge region; docking which incorporates protein side chain flexibility for selected residues in the ATP binding site resulted in a refinement of the water-mediated hinge binding mode that is consistent with observed SAR. The flexible docking results are in good agreement with the crystal structures of four exemplar benzimidazole ligands bound to CHK2 which unambiguously confirmed the binding mode of these inhibitors, including the water-mediated interaction with the hinge region, and which is significantly different from binding modes previously postulated in the literature. PMID:23058106

  6. Focus on PNA Flexibility and RNA Binding using Molecular Dynamics and Metadynamics (United States)

    Verona, Massimiliano Donato; Verdolino, Vincenzo; Palazzesi, Ferruccio; Corradini, Roberto


    Peptide Nucleic Acids (PNAs) can efficiently target DNA or RNA acting as chemical tools for gene regulation. Their backbone modification and functionalization is often used to increase the affinity for a particular sequence improving selectivity. The understanding of the trading forces that lead the single strand PNA to bind the DNA or RNA sequence is preparatory for any further rational design, but a clear and unique description of this process is still not complete. In this paper we report further insights into this subject, by a computational investigation aiming at the characterization of the conformations of a single strand PNA and how these can be correlated to its capability in binding DNA/RNA. Employing Metadynamics we were able to better define conformational pre-organizations of the single strand PNA and γ-modified PNA otherwise unrevealed through classical molecular dynamics. Our simulations driven on backbone modified PNAs lead to the conclusion that this γ-functionalization affects the single strand preorganization and targeting properties to the DNA/RNA, in agreement with circular dichroism (CD) spectra obtained for this class of compounds. MD simulations on PNA:RNA dissociation and association mechanisms allowed to reveal the critical role of central bases and preorganization in the binding process.

  7. Cooperative regulation of myosin-S1 binding to actin filaments by a continuous flexible Tm-Tn chain. (United States)

    Mijailovich, Srboljub M; Kayser-Herold, Oliver; Li, Xiaochuan; Griffiths, Hugh; Geeves, Michael A


    The regulation of striated muscle contraction involves cooperative interactions between actin filaments, myosin-S1 (S1), tropomyosin (Tm), troponin (Tn), and calcium. These interactions are modeled by treating overlapping tropomyosins as a continuous flexible chain (CFC), weakly confined by electrostatic interactions with actin. The CFC is displaced locally in opposite directions on the actin surface by the binding of either S1 or Troponin I (TnI) to actin. The apparent rate constants for myosin and TnI binding to and detachment from actin are then intrinsically coupled via the CFC model to the presence of neighboring bound S1s and TnIs. Monte Carlo simulations at prescribed values of the CFC stiffness, the CFC's degree of azimuthal confinement, and the angular displacements caused by the bound proteins were able to predict the stopped-flow transients of S1 binding to regulated F-actin. The transients collected over a large range of calcium concentrations could be well described by adjusting a single calcium-dependent parameter, the rate constant of TnI detachment from actin, k(-I). The resulting equilibrium constant K(B) ≡ 1/K(I) varied sigmoidally with the free calcium, increasing from 0.12 at low calcium (pCa >7) to 12 at high calcium (pCa Hill coefficient of ~2.15. The similarity of the curves for excess-actin and excess-myosin data confirms their allosteric relationship. The spatially explicit calculations confirmed variable sizes for the cooperative units and clustering of bound myosins at low calcium concentrations. Moreover, inclusion of negative cooperativity between myosin units predicted the observed slowing of myosin binding at excess-myosin concentrations.

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

    Indian Academy of Sciences (India)

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


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

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


    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.

  10. Implications of binding mode and active site flexibility for inhibitor potency against the salicylate synthase from Mycobacterium tuberculosis. (United States)

    Chi, Gamma; Manos-Turvey, Alexandra; O'Connor, Patrick D; Johnston, Jodie M; Evans, Genevieve L; Baker, Edward N; Payne, Richard J; Lott, J Shaun; Bulloch, Esther M M


    MbtI is the salicylate synthase that catalyzes the first committed step in the synthesis of the iron chelating compound mycobactin in Mycobacterium tuberculosis. We previously developed a series of aromatic inhibitors against MbtI based on the reaction intermediate for this enzyme, isochorismate. The most potent of these inhibitors had hydrophobic substituents, ranging in size from a methyl to a phenyl group, appended to the terminal alkene of the enolpyruvyl group. These compounds exhibited low micromolar inhibition constants against MbtI and were at least an order of magnitude more potent than the parental compound for the series, which carries a native enolpyruvyl group. In this study, we sought to understand how the substituted enolpyruvyl group confers greater potency, by determining cocrystal structures of MbtI with six inhibitors from the series. A switch in binding mode at the MbtI active site is observed for inhibitors carrying a substituted enolpyruvyl group, relative to the parental compound. Computational studies suggest that the change in binding mode, and higher potency, is due to the effect of the substituents on the conformational landscape of the core inhibitor structure. The crystal structures and fluorescence-based thermal shift assays indicate that substituents larger than a methyl group are accommodated in the MbtI active site through significant but localized flexibility in the peptide backbone. These findings have implications for the design of improved inhibitors of MbtI, as well as other chorismate-utilizing enzymes from this family.

  11. 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: [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)


    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.

  12. Calcium binding by the PKD1 domain regulates interdomain flexibility in Vibrio cholerae metalloprotease PrtV. (United States)

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


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

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

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

    Märtlbauer, E.


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

  15. Increased structural flexibility at the active site of a fluorophore-conjugated beta-lactamase distinctively impacts its binding toward diverse cephalosporin antibiotics. (United States)

    Wong, Wai-Ting; Chan, Kwok-Chu; So, Pui-Kin; Yap, Hong-Kin; Chung, Wai-Hong; Leung, Yun-Chung; Wong, Kwok-Yin; Zhao, Yanxiang


    The Ω-loop at the active site of β-lactamases exerts significant impact on the kinetics and substrate profile of these enzymes by forming part of the substrate binding site and posing as steric hindrance toward bulky substrates. Mutating certain residues on the Ω-loop has been a general strategy for molecular evolution of β-lactamases to expand their hydrolytic activity toward extended-spectrum antibiotics through a mechanism believed to involve enhanced structural flexibility of the Ω-loop. Yet no structural information is available that demonstrates such flexibility or its relation to substrate profile and enzyme kinetics. Here we report an engineered β-lactamase that contains an environment-sensitive fluorophore conjugated near its active site to probe the structural dynamics of the Ω-loop and to detect the binding of diverse substrates. Our results show that this engineered β-lactamase has improved binding kinetics and positive fluorescence signal toward oxyimino-cephalosporins, but shows little such effect to non-oxyimino-cephalosporins. Structural studies reveal that the Ω-loop adopts a less stabilized structure, and readily undergoes conformational change to accommodate the binding of bulky oxyimino-cephalosporins while no such change is observed for non-oxyimino-cephalosporins. Mutational studies further confirm that this substrate-induced structural change is directly responsible for the positive fluorescence signal specific to oxyimino-cephalosporins. Our data provide mechanistic evidence to support the long-standing model that the evolutionary strategy of mutating the Ω-loop leads to increased structural flexibility of this region, which in turn facilitates the binding of extended spectrum β-lactam antibiotics. The oxyimino-cephalosporin-specific fluorescence profile of our engineered β-lactamase also demonstrates the possibility of designing substrate-selective biosensing systems.

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

    Directory of Open Access Journals (Sweden)

    Kumar Shivesh


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

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

    Institute of Scientific and Technical Information of China (English)

    Yong Wang; Frederick C.C. Leung


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

  18. 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.


    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.

  19. 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


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

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

    Directory of Open Access Journals (Sweden)

    Mingming Gao

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

  1. Comparative experiments of graphene covalently and physically binding CdSe quantum dots to enhance the electron transport in flexible photovoltaic devices. (United States)

    Jung, Mi-Hee; Chu, Moo-Jung


    In this research, we prepared composite films via covalent coupling of CdSe quantum dots (QDs) to graphene through the direct binding of aryl radicals to the graphene surface. To compare the carrier transport with the CdSe aryl binding graphene film, we prepared CdSe pyridine capping graphene films through the pi-pi interactions of noncovalent bonds between the graphene and pyridine molecules. The photovoltaic devices were fabricated from the two hybrid films using the electrophoretic deposition method on flexible substrates. Even though the two hybrid films have the same amount of QDs and graphene, time-resolved fluorescence emission decay results show that the emission lifetime of the CdSe aryl group binding graphene film is significantly shorter than that of the pyridine capping CdSe-graphene. The quantum efficiency and photocurrent density of the device fabricated from CdSe aryl binding graphene were also higher than those of the device fabricated from pyridine capping CdSe-graphene. These results indicated that the carrier transport of the QD-graphene system is not related to the additive effect from the CdSe and graphene components but rather is a result of the unique interactions between the graphene and QDs. We could expect that these results can be useful in designing QD-graphene composite materials, which are applied in photovoltaic devices.

  2. Porphyrin Binding to Gun4 Protein, Facilitated by a Flexible Loop, Controls Metabolite Flow through the Chlorophyll Biosynthetic Pathway. (United States)

    Kopečná, Jana; Cabeza de Vaca, Israel; Adams, Nathan B P; Davison, Paul A; Brindley, Amanda A; Hunter, C Neil; Guallar, Victor; Sobotka, Roman


    In oxygenic phototrophs, chlorophylls, hemes, and bilins are synthesized by a common branched pathway. Given the phototoxic nature of tetrapyrroles, this pathway must be tightly regulated, and an important regulatory role is attributed to magnesium chelatase enzyme at the branching between the heme and chlorophyll pathway. Gun4 is a porphyrin-binding protein known to stimulate in vitro the magnesium chelatase activity, but how the Gun4-porphyrin complex acts in the cell was unknown. To address this issue, we first performed simulations to determine the porphyrin-docking mechanism to the cyanobacterial Gun4 structure. After correcting crystallographic loop contacts, we determined the binding site for magnesium protoporphyrin IX. Molecular modeling revealed that the orientation of α6/α7 loop is critical for the binding, and the magnesium ion held within the porphyrin is coordinated by Asn-211 residue. We also identified the basis for stronger binding in the Gun4-1 variant and for weaker binding in the W192A mutant. The W192A-Gun4 was further characterized in magnesium chelatase assay showing that tight porphyrin binding in Gun4 facilitates its interaction with the magnesium chelatase ChlH subunit. Finally, we introduced the W192A mutation into cells and show that the Gun4-porphyrin complex is important for the accumulation of ChlH and for channeling metabolites into the chlorophyll biosynthetic pathway.

  3. Ligand binding to an Allergenic Lipid Transfer Protein Enhances Conformational Flexibility resulting in an Increase in Susceptibility to Gastroduodenal Proteolysis (United States)

    Abdullah, Syed Umer; Alexeev, Yuri; Johnson, Philip E.; Rigby, Neil M.; Mackie, Alan R.; Dhaliwal, Balvinder; Mills, E. N. Clare


    Non-specific lipid transfer proteins (LTPs) are a family of lipid-binding molecules that are widely distributed across flowering plant species, many of which have been identified as allergens. They are highly resistant to simulated gastroduodenal proteolysis, a property that may play a role in determining their allergenicity and it has been suggested that lipid binding may further increase stability to proteolysis. It is demonstrated that LTPs from wheat and peach bind a range of lipids in a variety of conditions, including those found in the gastroduodenal tract. Both LTPs are initially cleaved during gastroduodenal proteolysis at three major sites between residues 39–40, 56–57 and 79–80, with wheat LTP being more resistant to cleavage than its peach ortholog. The susceptibility of wheat LTP to proteolyic cleavage increases significantly upon lipid binding. This enhanced digestibility is likely to be due to the displacement of Tyr79 and surrounding residues from the internal hydrophobic cavity upon ligand binding to the solvent exposed exterior of the LTP, facilitating proteolysis. Such knowledge contributes to our understanding as to how resistance to digestion can be used in allergenicity risk assessment of novel food proteins, including GMOs.

  4. Genome-scale analysis of metazoan replication origins reveals their organization in specific but flexible sites defined by conserved features (United States)

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


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

  5. Ca(2+)-binding reduces conformational flexibility of RC-LH1 core complex from thermophile Thermochromatium tepidum. (United States)

    Jakob-Grun, Selma; Radeck, Jara; Braun, Paula


    The light-harvesting complex, LH1, of thermophile purple bacteria Thermochromatium tepidum consists of an array of α- and β-polypeptides which assemble the photoactive bacteriochlorophyll and closely interact with the membrane-lipids. In this study, we investigated the effect of calcium and manganese ions on the protein structure and thermostability of the reaction centre (RC)-LH1/lipid complex. The binding of Ca(2+), but not Mn(2+) is shown to shift the LH1 Q ( y ) absorption maximum from ~889 to 915 nm and to significantly raise the thermostability of the RC-LH1 complex. The ATR-FTIR spectra indicate that interaction of Ca(2+) as monitored by the carboxylates' vibration of aspartate residues, but not Mn(2+) induces changes in the α-helix packing arrangement. The reduced rate of (1)H/(2)H exchange of proteins' amide protons shows that the accessibility to (2)H(2)O is significantly lowered in Ca(2+)-substituted RC-LH1/lipid complexes. In particular, exchange with the associated lipid molecules, is significantly retarded. These results suggest that the thermostability of the RC-LH1 complex is raised by the distinct interaction with calcium cations which reduces the RC-LH1/lipid dynamics, particularly, at the membrane-water interface.

  6. Short GC-rich RNA similar to miR 1909 and 1915 folds in silico with the 5'-UTR and ORF of Notch and responders: potential for the elimination of cancer stem cells. (United States)

    Li, Yufeng; Mine, Takashi; Ioannides, Constantin G


    Novel therapeutic approaches to eliminate cancer stem cells (CSCs) are being developed. This development is imperative as CSCs are resistant to drugs; they divide activated by ligands on the epithelium or on neighboring cancer cells. Specific commands for division originate from Notch-1 ligands. Notch-1 cleavage inhibitors can have opposite effects from the ones expected when the levels of Notch ligands are high on neighboring cancer cells. High levels of Jagged-1 are a common feature of ovarian tumors. Some gene pathways enhance, others repress transcription of Notch-1, while Notch-1 itself activates Myc and HIF-1α. RNA-based therapies need effector RNAs (eRNAs) with broad and focused specificity. eRNAs are short RNAs (20-30 nt long) which mediate biological effects. Two to three inhibitory RNAs with high net folding/hybridization/binding (and thereafter folding), and free energy (Net-ΔG) with multiple mRNAs can replace many miRs as eRNAs and overcome the complexity of identification of specific targets for each miR and competitive inhibition on delivery of small amounts of many miRs at the same time. To discover candidate eRNAs with multiple high affinity target sites or sequences (and thereafter targets), we searched for sequences containing more than randomly probable G and C. G and C bind with more hydrogen bonds than the pair A:T. We identified the sequence, Notch-1,33-56 in the ORF of Notch-1 mRNA. Notch-1,33-56 has a GC frame of 2 asymmetrical halves in 24 nucleotides. Each GC group has a different third nucleotide. Since GC is repeated, the third nucleotide defines the specificity as a 'bar code'. The complementary strand to Notch-1,33-56, binds in silico nt at 5'-UTR, ORF and 3'-UTR of mRNA. For simplification, the sequence of Notch-1,33-56 was designated HHN1 and its complementary strand, anti-HHB. We introduced novel quantitative parameters: Net-ΔG and mean Net-ΔG/bond. We quantified the Net-ΔG of folding, in silico, of anti-HHB with additional

  7. Flexible supercapacitors

    Institute of Scientific and Technical Information of China (English)

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


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

  8. Flexible Software for Flexible Scheduling (United States)

    Economou, Frossie; Jenness, Tim; Tilanus, Remo P. J.; Hirst, Paul; Adamson, Andy J.; Rippa, Mathew; Delorey, Kynan K.; Isaak, Kate G.

    The JAC Observation Management Project (OMP) provides software for the James Clerk Maxwell (JCMT) and the United Kingdom Infrared (UKIRT) telescopes that manages the life-cycle of flexibly scheduled observations. Its aim is to increase observatory efficiency under flexible (queue) scheduled observing, without depriving the principal investigator (PI) of the flexibility associated with classical scheduling.


    NARCIS (Netherlands)



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

  10. Forgiveness Flexibility

    Directory of Open Access Journals (Sweden)

    Tuğba Seda Çolak


    Full Text Available Forgiveness flexibility is the skill to minimize the negative effect of an event by using cognitive, affective and behavioral skills while taking a stand at the end of an injurious process. A number of studies were conducted to test the flexibility of the structure of forgiveness. The theoretical structure, structural validity and the confirmatory factor analysis supported the theoretical structure of forgiveness flexibility. The criterion validity evaluated in similar manners was found high. Forgiveness flexibility designed as a three dimensional structure and its sub-dimensions was confirmed theoretically as the recognition of forgivenessand the internalization of forgiveness through insight and its practice.

  11. Two Distantly Spaced Basic Patches in the Flexible Domain of Huntingtin-Interacting Protein 1 (HIP1 Are Essential for the Binding of Clathrin Light Chain

    Directory of Open Access Journals (Sweden)

    Joel A. Ybe


    Full Text Available The interaction between HIP family proteins (HIP1 and HIP12/1R and clathrin is fundamental to endocytosis. We used circular dichroism (CD to study the stability of an HIP1 subfragment (aa468-530 that is splayed open. CD thermal melts show HIP1 468-530 is only stable at low temperatures, but this HIP1 fragment contains a structural unit that does not melt out even at 83C∘. We then created HIP1 mutants to probe our hypothesis that a short hydrophobic path in the opened region is the binding site for clathrin light chain. We found that the binding of hub/LCb was sensitive to mutating two distantly separated basic residues (K474 and K494. The basic patches marked by K474 and K494 are conserved in HIP12/1R. The lack of conservation in sla2p (S. cerevisiae, HIP1 from D. melanogaster, and HIP1 homolog ZK370.3 from C. elegans implies the binding of HIP1 and HIP1 homologs to clathrin light chain may be different in these organisms.

  12. 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:; Subedi, Ganesh P. [Iowa State University, Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology (United States)


    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.

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

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


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

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

  15. The crystal structure of the D-alanine-D-alanine ligase from Acinetobacter baumannii suggests a flexible conformational change in the central domain before nucleotide binding. (United States)

    Huynh, Kim-Hung; Hong, Myoung-ki; Lee, Clarice; Tran, Huyen-Thi; Lee, Sang Hee; Ahn, Yeh-Jin; Cha, Sun-Shin; Kang, Lin-Woo


    Acinetobacter baumannii, which is emerging as a multidrug-resistant nosocomial pathogen, causes a number of diseases, including pneumonia, bacteremia, meningitis, and skin infections. With ATP hydrolysis, the D-alanine-D-alanine ligase (DDL) catalyzes the synthesis of D-alanyl-D-alanine, which is an essential component of bacterial peptidoglycan. In this study, we determined the crystal structure of DDL from A. baumannii (AbDDL) at a resolution of 2.2 Å. The asymmetric unit contained six protomers of AbDDL. Five protomers had a closed conformation in the central domain, while one protomer had an open conformation in the central domain. The central domain with an open conformation did not interact with crystallographic symmetry-related protomers and the conformational change of the central domain was not due to crystal packing. The central domain of AbDDL can have an ensemble of the open and closed conformations before the binding of substrate ATP. The conformational change of the central domain is important for the catalytic activity and the detail information will be useful for the development of inhibitors against AbDDL and putative antibacterial agents against A. baumannii. The AbDDL structure was compared with that of other DDLs that were in complex with potent inhibitors and the catalytic activity of AbDDL was confirmed using enzyme kinetics assays.

  16. Functional aspects of protein flexibility

    DEFF Research Database (Denmark)

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


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

  17. Piping Flexibility (United States)


    A NASA computer program aids Hudson Engineering Corporation, Houston, Texas, in the design and construction of huge petrochemical processing plants like the one shown, which is located at Ju'aymah, Saudi Arabia. The pipes handling the flow of chemicals are subject to a variety of stresses, such as weight and variations in pressure and temperature. Hudson Engineering uses a COSMIC piping flexibility analysis computer program to analyze stresses and unsure the necessary strength and flexibility of the pipes. This program helps the company realize substantial savings in reduced engineering time.

  18. Combining pharmacophore search, automated docking, and molecular dynamics simulations as a novel strategy for flexible docking. Proof of concept: docking of arginine-glycine-aspartic acid-like compounds into the alphavbeta3 binding site. (United States)

    Moitessier, Nicolas; Henry, Christophe; Maigret, Bernard; Chapleur, Yves


    A novel and highly efficient flexible docking approach is presented where the conformations (internal degrees of freedom) and orientations (external degrees of freedom) of the ligands are successively considered. This hybrid method takes advantage of the synergistic effects of structure-based and ligand-based drug design techniques. Preliminary antagonist-derived pharmacophore determination provides the postulated bioactive conformation. Subsequent docking of this pharmacophore to the receptor crystal structure results in a postulated pharmacophore/receptor binding mode. Pharmacophore-oriented docking of antagonists is subsequently achieved by matching ligand interacting groups with pharmacophore points. Molecular dynamics in water refines the proposed complexes. To validate the method, arginine-glycine-aspartic acid (RGD) containing peptides, pseudopeptides, and RGD-like antagonists were docked to the crystal structure of alphavbeta3 holoprotein and apoprotein. The proposed directed docking was found to be more accurate, faster, and less biased with respect to the protein structure (holo and apoprotein) than DOCK, Autodock, and FlexX docking methods. The successful docking of an antagonist recently cocrystallized with the receptor to both apo and holoprotein is particularly appealing. The results summarized in this report illustrated the efficiency of our light CoMFA/rigid body docking hybrid method.

  19. Protein stability, flexibility and function

    DEFF Research Database (Denmark)

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


    Proteins rely on flexibility to respond to environmental changes, ligand binding and chemical modifications. Potentially, a perturbation that changes the flexibility of a protein may interfere with its function. Millions of mutations have been performed on thousands of proteins in quests for a de......Proteins rely on flexibility to respond to environmental changes, ligand binding and chemical modifications. Potentially, a perturbation that changes the flexibility of a protein may interfere with its function. Millions of mutations have been performed on thousands of proteins in quests...... for a delineation of the molecular details of their function. Several of these mutations interfered with the binding of a specific ligand with a concomitant effect on the stability of the protein scaffold. It has been ambiguous and not straightforward to recognize if any relationships exist between the stability...... of a protein and the affinity for its ligand. In this review, we present examples of proteins where changes in stability results in changes in affinity and of proteins where stability and affinity are uncorrelated. We discuss the possibility for a relationship between stability and binding. From the data...

  20. 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...

  1. DAPI binding to the DNA minor groove: a continuum solvent analysis. (United States)

    De Castro, L F Pineda; Zacharias, M


    A continuum solvent model based on the generalized Born (GB) or finite-difference Poisson-Boltzmann (FDPB) approaches has been employed to compare the binding of 4'-6-diamidine-2-phenyl indole (DAPI) to the minor groove of various DNA sequences. Qualitative agreement between the results of GB and FDPB approaches as well as between calculated and experimentally observed trends regarding the sequence specificity of DAPI binding to B-DNA was obtained. Calculated binding energies were decomposed into various contributions to solvation and DNA-ligand interaction. DNA conformational adaptation was found to make a favorable contribution to the calculated total interaction energy but did not change the DAPI binding affinity ranking of different DNA sequences. The calculations indicate that closed complex formation is mainly driven by nonpolar contributions and was found to be disfavored electrostatically due to a desolvation penalty that outbalances the attractive Coulomb interaction. The calculated penalty was larger for DAPI binding to GC-rich sequences compared with AT-rich target sequences and generally larger for the FDPB vs the GB continuum model. A radial interaction profile for DAPI at different distances from the DNA minor groove revealed an electrostatic energy minimum a few Angstroms farther away from the closed binding geometry. The calculated electrostatic interaction up to this distance is attractive and it may stabilize a nonspecific binding arrangement.

  2. Flexible Electronics Research Facility (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...

  3. Genetic flexibility of regulatory networks. (United States)

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


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

  4. Protein Binding Pocket Dynamics. (United States)

    Stank, Antonia; Kokh, Daria B; Fuller, Jonathan C; Wade, Rebecca C


    The dynamics of protein binding pockets are crucial for their interaction specificity. Structural flexibility allows proteins to adapt to their individual molecular binding partners and facilitates the binding process. This implies the necessity to consider protein internal motion in determining and predicting binding properties and in designing new binders. Although accounting for protein dynamics presents a challenge for computational approaches, it expands the structural and physicochemical space for compound design and thus offers the prospect of improved binding specificity and selectivity. A cavity on the surface or in the interior of a protein that possesses suitable properties for binding a ligand is usually referred to as a binding pocket. The set of amino acid residues around a binding pocket determines its physicochemical characteristics and, together with its shape and location in a protein, defines its functionality. Residues outside the binding site can also have a long-range effect on the properties of the binding pocket. Cavities with similar functionalities are often conserved across protein families. For example, enzyme active sites are usually concave surfaces that present amino acid residues in a suitable configuration for binding low molecular weight compounds. Macromolecular binding pockets, on the other hand, are located on the protein surface and are often shallower. The mobility of proteins allows the opening, closing, and adaptation of binding pockets to regulate binding processes and specific protein functionalities. For example, channels and tunnels can exist permanently or transiently to transport compounds to and from a binding site. The influence of protein flexibility on binding pockets can vary from small changes to an already existent pocket to the formation of a completely new pocket. Here, we review recent developments in computational methods to detect and define binding pockets and to study pocket dynamics. We introduce five

  5. Docking to flexible nicotinic acetylcholine receptors

    DEFF Research Database (Denmark)

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


    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...

  6. 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.


    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 manu

  7. 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

    NARCIS (Netherlands)

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


    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 f

  8. Specificity and Affinity Quantification of Flexible Recognition from Underlying Energy Landscape Topography (United States)

    Chu, Xiakun; Wang, Jin


    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. PMID:25144525

  9. Binding S0.6 Se0.4 in 1D Carbon Nanofiber with CS Bonding for High-Performance Flexible Li-S Batteries and Na-S Batteries. (United States)

    Yao, Yu; Zeng, Linchao; Hu, Shuhe; Jiang, Yu; Yuan, Beibei; Yu, Yan


    A one-step synthesis procedure is developed to prepare flexible S0.6 Se0.4 @carbon nanofibers (CNFs) electrode by coheating S0.6 Se0.4 powder with electrospun polyacrylonitrile nanofiber papers at 600 °C. The obtained S0.6 Se0.4 @CNFs film can be used as cathode material for high-performance Li-S batteries and room temperature (RT) Na-S batteries directly. The superior lithium/sodium storage performance derives from its rational structure design, such as the chemical bonding between Se and S, the chemical bonding between S0.6 Se0.4 and CNFs matrix, and the 3D CNFs network. This easy one-step synthesis procedure provides a feasible route to prepare electrode materials for high-performance Li-S and RT Na-S batteries.

  10. Global Sourcing Flexibility

    DEFF Research Database (Denmark)

    Ørberg Jensen, Peter D.; Petersen, Bent


    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......Recent studies show that flexibility is a key concern for firms that engage in the global sourcing of services. In this conceptual paper, we seek to explore two central aspects of global sourcing flexibility: In the first part of the paper, we provide a definition of the construct of global...... 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...

  11. Pneumatic flexible shaft couplings



    Main effort of every design engineer is reduction of torsional oscillation in any mechanical system. At present this problem can be solved by means of a suitable modification of dynamic properties of flexible shaft couplings according to dynamics in the given systems. But the dynamic properties of nowadays-applied flexible couplings arenot unchangeable because of aging and fatigue processes occurring in flexible coupling elements. Result of this fact causes detuning of mechanical system. Taki...

  12. Reversibly Bistable Flexible Electronics

    KAUST Repository

    Alfaraj, Nasir


    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.

  13. Flexible 'zoning' aids adaptability. (United States)

    Corben, Simon


    Simon Corben, business development director at Capita Symonds' Health team, examines how 'clever use of zoning' when planning new healthcare facilities could improve hospital design, increase inherent flexibility, and reduce lifetime costs, and argues that a 'loose-fit, non-bespoke approach' to space planning will lead to 'more flexible buildings that are suitable for conversion to alternative uses'.

  14. Flexible magnetoimpidence sensor

    KAUST Repository

    Kavaldzhiev, Mincho


    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.

  15. Flexible Carbon Aerogels

    Directory of Open Access Journals (Sweden)

    Marina Schwan


    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.

  16. Flexible ferroelectric organic crystals (United States)

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


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

  17. Flexible ferroelectric organic crystals (United States)

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


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

  18. 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;


    Introduction: Genomic base composition ranges from less than 25% AT to more than 85% AT in prokaryotes. Since only a small fraction of prokaryotic genomes is not protein coding even a minor change in genomic base composition will induce profound protein changes. We examined how amino acid and codon...

  19. Methods for sequencing GC-rich and CCT repeat DNA templates (United States)

    Robinson, Donna L.


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

  20. Flexible graphene-based lithium ion batteries with ultrafast charge and discharge rates


    Li, Na; Chen, Zongping; Ren, Wencai; LI Feng; Cheng, Hui-Ming


    There is growing interest in thin, lightweight, and flexible energy storage devices to meet the special needs for next-generation, high-performance, flexible electronics. Here we report a thin, lightweight, and flexible lithium ion battery made from graphene foam, a three-dimensional, flexible, and conductive interconnected network, as a current collector, loaded with Li4Ti5O12 and LiFePO4, for use as anode and cathode, respectively. No metal current collectors, conducting additives, or binde...

  1. Painful Flexible Flatfoot. (United States)

    Sheikh Taha, Abdel Majid; Feldman, David S


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

  2. Flexible displays, rigid designs?

    DEFF Research Database (Denmark)

    Hornbæk, Kasper


    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....

  3. 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.


    Institute of Scientific and Technical Information of China (English)

    GAO Zhihui; YUN Chao; BIAN Yushu


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

  5. Binding Procurement (United States)

    Rao, Gopalakrishna M.; Vaidyanathan, Hari


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

  6. Flexible magnetoimpedance sensor

    Energy Technology Data Exchange (ETDEWEB)

    Li, Bodong; Kavaldzhiev, Mincho N.; Kosel, Jürgen, E-mail:


    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.

  7. Service-based flexible workflow system for virtual enterprise

    Institute of Scientific and Technical Information of China (English)

    WU Shao-fei


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

  8. Flexible magnetoimpedance sensor

    KAUST Repository

    Li, Bodong


    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.

  9. Pneumatic flexible shaft couplings

    Directory of Open Access Journals (Sweden)

    Jaroslav HOMIŠIN


    Full Text Available Main effort of every design engineer is reduction of torsional oscillation in any mechanical system. At present this problem can be solved by means of a suitable modification of dynamic properties of flexible shaft couplings according to dynamics in the given systems. But the dynamic properties of nowadays-applied flexible couplings arenot unchangeable because of aging and fatigue processes occurring in flexible coupling elements. Result of this fact causes detuning of mechanical system. Taking into consideration the above-mentioned situation, we suggest for mechanical systems application of a newly developed pneumatic couplings that have constant characteristicfeatures during the whole current operation and thus they have a positive influence on the system running.

  10. Thin flexible intercalation anodes

    Energy Technology Data Exchange (ETDEWEB)

    Levy, S.C.; Cieslak, W.R.; Klassen, S.E.; Lagasse, R.R.


    Poly(acrylonitrile) fibers have been pyrolyzed under various conditions to form flexible carbon yarns capable of intercalating lithium ions. These fibers have also been formed into both woven and non woven cloths. Potentiostatic, potentiodynamic and galvanostatic tests have been conducted with these materials in several electrolytes. In some tests, a potential hold was used after each constant current charge and discharge. These tests have shown some of these flexible materials to reversibly intercalate lithium ions to levels that are suitable for use as a practical battery anode.

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

    CERN Document Server

    Suhonen, P M


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

  12. Flexible metal bellows

    CERN Multimedia


    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.

  13. Flexible Classroom Furniture (United States)

    Kim Hassell,


    Classroom design for the 21st-century learning environment should accommodate a variety of learning skills and needs. The space should be large enough so it can be configured to accommodate a number of learning activities. This also includes furniture that provides flexibility and accommodates collaboration and interactive work among students and…

  14. 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 ...

  15. Flexible energy systems

    DEFF Research Database (Denmark)

    Lund, Henrik


    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....

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

    Directory of Open Access Journals (Sweden)

    Tatyana Aleksandrovna Khrustaleva


    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.

  17. Adding flexibility to physician training. (United States)

    Mahady, Suzanne E


    Demographic changes among junior doctors are driving demand for increased flexibility in advanced physician training, but flexible training posts are lacking. Suitable flexible training models include flexible full-time, job-share and part-time positions. Major barriers to establishing flexible training positions include difficulty in finding job-share partners, lack of funding for creating supernumerary positions, and concern over equivalence of educational quality compared with full-time training. Pilot flexible training positions should be introduced across the medical specialties and educational outcomes examined prospectively.

  18. Aggregating energy flexibilities under constraints

    DEFF Research Database (Denmark)

    Valsomatzis, Emmanouil; Pedersen, Torben Bach; Abello, Alberto


    The flexibility of individual energy prosumers (producers and/or consumers) has drawn a lot of attention in recent years. Aggregation of such flexibilities provides prosumers with the opportunity to directly participate in the energy market and at the same time reduces the complexity of scheduling...... the energy units. However, aggregated flexibility should support normal grid operation. In this paper, we build on the flex-offer (FO) concept to model the inherent flexibility of a prosumer (e.g., a single flexible consumption device such as a clothes washer). An FO captures flexibility in both time...

  19. Flexible Laser Metal Cutting

    DEFF Research Database (Denmark)

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


    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....

  20. Flexible Metasurface Holograms

    CERN Document Server

    Burch, James; Chen, Xianzhong; Di Falco, Andrea


    Metasurface holograms are typically fabricated on rigid substrates. Here we experimentally demonstrate broadband, flexible, conformable, helicity multiplexed metasurface holograms operating in the visible range, offering increased potential for real life out-of-the-lab applications. Two symmetrically distributed holographic images are obtained when circularly polarized light impinges on the reflective-type metasurface positioned on non- planar targets. The two off-axis images with high fidelity are interchangeable by controlling the helicity of incident light. Our metasurface features the arrangement of spatially varying gold nanorods on a flexible, conformable epoxy resist membrane to realize a Pancharatnam- Berry phase profile. These results pave the way to practical applications including polarization manipulation, beam steering, novel lenses, and holographic displays.


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


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

  2. More flexibility for DESY

    CERN Multimedia


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

  3. Flexible Land Administration

    DEFF Research Database (Denmark)

    Enemark, Stig


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

  4. Flexible Word Classes

    DEFF Research Database (Denmark)


    a century, the phenomenon has not played a role in the development of linguistic typology or modern grammatical theory. The current volume aims to address this gap by offering detailed studies on flexible word classes, investigating their properties and what it means for the grammar of a language to have...... Indonesian, Santali, Sri Lanka Malay, Lushootseed, Gooniyandi, and Late Archaic Chinese. Readership: Linguists and students of linguistics and cognitive sciences, anthropologists, philosophers...

  5. Industrial Fuel Flexibility Workshop

    Energy Technology Data Exchange (ETDEWEB)



    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.

  6. Flexible Data Link (United States)


    reconfiguring the waveform characteristics (on-the-fly) based on the engagement environment. Therefore, flexibility was the highest priority in the design of...the aircraft to a ground antenna . Utilizing the threshold system requirements (100 km range), we calculate the multipath of the aircraft as it...approaches the ground antenna . Figure 3: Multipath scenario #1 The calculation of the reflected path (denoted as A + C in Figure 3) is found through the

  7. Designing structural supply chain flexibility

    NARCIS (Netherlands)

    Mulinski, Ksawery Jan


    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

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

    Meena, Laxman S; Meena, Jaishree


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

  9. Measuring and Comparing Energy Flexibilities

    DEFF Research Database (Denmark)

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


    Flexibility in energy supply and demand becomes more and more important with increasing Renewable Energy Sources (RES) production and the emergence of the Smart Grid. So-called prosumers, i.e., entities that produce and/or consume energy, can offer their inherent flexibilities through so......-called demand response and thus help stabilize the energy markets. Thus, prosumer flexibility becomes valuable and the ongoing Danish project TotalFlex [1] explores the use of prosumer flexibility in the energy market using the concept of a flex-offer [2], which captures energy flexibilities in time and...... 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....

  10. Flexible Volumetric Structure (United States)

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


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

  11. Composite Flexible Blanket Insulation (United States)

    Kourtides, Demetrius A. (Inventor); Pitts, William C. (Inventor); Goldstein, Howard E. (Inventor); Sawko, Paul M. (Inventor)


    Composite flexible multilayer insulation systems (MLI) were evaluated for thermal performance and compared with the currently used fibrous silica (baseline) insulation system. The systems described are multilayer insulations consisting of alternating layers of metal foil and scrim ceramic cloth or vacuum metallized polymeric films quilted together using ceramic thread. A silicon carbide thread for use in the quilting and the method of making it are also described. These systems are useful in providing lightweight insulation for a variety of uses, particularly on the surface of aerospace vehicles subject to very high temperatures during flight.

  12. Flexible composite radiation detector (United States)

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


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

  13. Flexible plasma linear antenna (United States)

    Zhao, Jiansen; Wang, Shengzheng; Wu, Huafeng; Liu, Yue; Chang, Yongmeng; Chen, Xinqiang


    In this work, we introduce a type of plasma antenna that was fabricated using flexible materials and excited using a 5-20 kHz alternating current (ac) power supply. The results showed that the antenna characteristics, including the impedance, the reflection coefficient (S11), the radiation pattern, and the gain, can be controlled rapidly and easily by varying both the discharge parameters and the antenna shapes. The scope for reconfiguration is greatly enhanced when the antenna shape is changed from a monopole to a helix configuration. Additionally, the antenna polarization can also be adjusted by varying the antenna shapes.

  14. Asymmetric Flexible Supercapacitor Stack

    Directory of Open Access Journals (Sweden)

    Leela Mohana Reddy A


    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.

  15. The Flexibility Hypothesis of Healing. (United States)

    Hinton, Devon E; Kirmayer, Laurence J


    Theories of healing have attempted to identify general mechanisms that may work across different modalities. These include altering expectations, remoralization, and instilling hope. In this paper, we argue that many forms of healing and psychotherapy may work by inducing positive psychological states marked by flexibility or an enhanced ability to shift cognitive sets. Healing practices may induce these states of cognitive and emotional flexibility through specific symbolic interventions we term "flexibility primers" that can include images, metaphors, music, and other media. The flexibility hypothesis suggests that cognitive and emotional flexibility is represented, elicited, and enacted through multiple modalities in healing rituals. Identifying psychological processes and cultural forms that evoke and support cognitive and emotional flexibility provides a way to understand the cultural specificity and potential efficacy of particular healing practices and can guide the design of interventions that promote resilience and well-being.

  16. Conformation-controlled binding kinetics of antibodies (United States)

    Galanti, Marta; Fanelli, Duccio; Piazza, Francesco


    Antibodies are large, extremely flexible molecules, whose internal dynamics is certainly key to their astounding ability to bind antigens of all sizes, from small hormones to giant viruses. In this paper, we build a shape-based coarse-grained model of IgG molecules and show that it can be used to generate 3D conformations in agreement with single-molecule Cryo-Electron Tomography data. Furthermore, we elaborate a theoretical model that can be solved exactly to compute the binding rate constant of a small antigen to an IgG in a prescribed 3D conformation. Our model shows that the antigen binding process is tightly related to the internal dynamics of the IgG. Our findings pave the way for further investigation of the subtle connection between the dynamics and the function of large, flexible multi-valent molecular machines.

  17. Flexible cultural repertoires

    DEFF Research Database (Denmark)

    Lindegaard, Marie Rosenkrantz


    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...... varying cultural repertoires, in particularly heterogeneous flexible repertoires, influence offending and victimization patterns among young men in high-risk settings....... 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...

  18. Conformational flexibility of aspartame. (United States)

    Toniolo, Claudio; Temussi, Pierandrea


    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.

  19. Building Highly Flexible Polyelectrolyte Nanotubes

    Institute of Scientific and Technical Information of China (English)


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

  20. Flexible Stamp for Nanoimprint Lithography

    DEFF Research Database (Denmark)

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


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

  1. Sensor Technologies on Flexible Substrates (United States)

    Koehne, Jessica


    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. On flexible and rigid nouns

    DEFF Research Database (Denmark)

    Rijkhoff, Jan


    , 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...

  3. On flexible and rigid nouns

    DEFF Research Database (Denmark)

    Rijkhoff, Jan


    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...

  4. Flexible Coupling Corrects Shaft Misalinements (United States)

    Mayo, R. A.


    Proposed flexible coupling provides nearly error free measurements of shaft rotation in presence of misalinements between shaft and position sensing transducer. Intended to be used in situations in which input or output shaft is mounted on flexible joint. Its function is to insure equal input and output angular velocities by forcing input and output shafts to remain parallel.

  5. [Flexible root posts]. (United States)

    Vadachkoriia, N R; Mandzhavidze, N A; Gumberidze, N Sh


    The article discusses the current state of restoration techniques of root canal treatment. Nowadays, technical progress allows manufacturers to develop flexible fiberglass posts, aspiring not only to an excellent aesthetics and mechanical properties (first of all, in comparison with metal and cast posts), but also to maintenance of their radio density and a wide range of forms. Growth of fiberglass posts popularity testifies to their clinical efficiency that also is confirmed by results of long-term researches. Introduction of fiberglass posts in a dental practice has rendered huge influence on restoration techniques of root canal treatment. Convincing factors of fiberglass posts superiority provide restoration the appearance similar with the natural dentition; possess close to dentine elasticity; creation of monolithic structure with hard tooth tissues and composite cement, posts, in case of need, can be easily adjusted on length, adhesive linkage of posts gives them additional stability. Modern researches have confirmed that only elastic, namely carbon fiber and the fiberglass posts made of modern technologies possess similar physical properties, as tooth structure. They can create reliable biomimetic design; solve a complex of aesthetic and functional restoration problems.

  6. Orthogonal flexible Rydberg aggregates (United States)

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


    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.

  7. Orthogonal flexible Rydberg aggregates

    CERN Document Server

    Leonhardt, K; Rost, J M


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

  8. Multifunctional, flexible electronic systems based on engineered nanostructured materials. (United States)

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


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

  9. Flexible Blades for Wind Turbines (United States)

    Collins, Madeline Carlisle; Macphee, David; Harris, Caleb


    Previous research has shown that windmills with flexible blades are more efficient than those with rigid blades. Flexibility offers passive pitch control, preferable to active pitch control which is costly and requires maintenance. Flexible blades morph such that the blade more closely resembles its design point at part load and over load. The lift-to-drag ratios on individual blades was investigated. A mold was designed and machined from an acrylic slab for the casting of blades with a NACA 0012 cross section. A flexible blade was cast from silicone and a rigid blade was cast from polyurethane. Each of these blades was tested in a wind tunnel, cantilever mounted, spanning the whole test section. The angle of attack was varied by rotating the mount. All tests were performed at the same wind speed. A load cell within the mount measured forces on the blade, from which the lift and drag forces were calculated. The stall point for the flexible blade occurred later than for the rigid blade, which agrees with previous research. Lift-to-drag ratios were larger for the flexible blade at all angles of attack tested. Flexible blades seem to be a viable option for passive pitch control. Future research will include different airfoil cross sections, wind speeds, and blade materials. Funding from NSF REU site Grant EEC 1358991 is greatly appreciated.

  10. Flexible armored blanket development

    Energy Technology Data Exchange (ETDEWEB)

    Roth, E.S.


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

  11. Swarming: flexible roaming plans. (United States)

    Partridge, Jonathan D; Harshey, Rasika M


    Movement over an agar surface via swarming motility is subject to formidable challenges not encountered during swimming. Bacteria display a great deal of flexibility in coping with these challenges, which include attracting water to the surface, overcoming frictional forces, and reducing surface tension. Bacteria that swarm on "hard" agar surfaces (robust swarmers) display a hyperflagellated and hyperelongated morphology. Bacteria requiring a "softer" agar surface (temperate swarmers) do not exhibit such a dramatic morphology. For polarly flagellated robust swarmers, there is good evidence that restriction of flagellar rotation somehow signals the induction of a large number of lateral flagella, but this scenario is apparently not relevant to temperate swarmers. Swarming bacteria can be further subdivided by their requirement for multiple stators (Mot proteins) or a stator-associated protein (FliL), secretion of essential polysaccharides, cell density-dependent gene regulation including surfactant synthesis, a functional chemotaxis signaling pathway, appropriate cyclic (c)-di-GMP levels, induction of virulence determinants, and various nutritional requirements such as iron limitation or nitrate availability. Swarming strategies are as diverse as the bacteria that utilize them. The strength of these numerous designs stems from the vantage point they offer for understanding mechanisms for effective colonization of surface niches, acquisition of pathogenic potential, and identification of environmental signals that regulate swarming. The signature swirling and streaming motion within a swarm is an interesting phenomenon in and of itself, an emergent behavior with properties similar to flocking behavior in diverse systems, including birds and fish, providing a convenient new avenue for modeling such behavior.

  12. Guideline Implementation: Processing Flexible Endoscopes. (United States)

    Bashaw, Marie A


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

  13. Flexible Learning in a Digital World. (United States)

    Collis, Betty; Moonen, Jef


    Defines flexible learning and describes components of flexible learning in higher education, including technology, pedagogy or instructional approach, implementation strategies, and institutional framework. Considers factors constraining learning flexibility; changing student characteristics; and the need for lifelong learning, particularly in the…

  14. A positive mood, a flexible brain


    Betzel, Richard F.; Satterthwaite, Theodore D.; Gold, Joshua I.; Bassett, Danielle S.


    Flexible reconfiguration of human brain networks supports cognitive flexibility and learning. However, modulating flexibility to enhance learning requires an understanding of the relationship between flexibility and brain state. In an unprecedented longitudinal data set, we investigate the relationship between flexibility and mood, demonstrating that flexibility is positively correlated with emotional state. Our results inform the modulation of brain state to enhance response to training in h...

  15. Flexible Transparent Electronic Gas Sensors. (United States)

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


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

  16. Flexible sensors based on nanoparticles. (United States)

    Segev-Bar, Meital; Haick, Hossam


    Flexible sensors can be envisioned as promising components for smart sensing applications, including consumer electronics, robotics, prosthetics, health care, safety equipment, environmental monitoring, homeland security and space flight. The current review presents a concise, although admittedly nonexhaustive, didactic review of some of the main concepts and approaches related to the use of nanoparticles (NPs) in flexible sensors. The review attempts to pull together different views and terminologies used in the NP-based sensors, mainly those established via electrical transduction approaches, including, but, not confined to: (i) strain-gauges, (ii) flexible multiparametric sensors, and (iii) sensors that are unaffected by mechanical deformation. For each category, the review presents and discusses the common fabrication approaches and state-of-the-art results. The advantages, weak points, and possible routes for future research, highlighting the challenges for NP-based flexible sensors, are presented and discussed as well.

  17. Aggregating and Disaggregating Flexibility Objects

    DEFF Research Database (Denmark)

    Siksnys, Laurynas; Valsomatzis, Emmanouil; Hose, Katja


    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...... energy data management and discuss strategies for aggregation and disaggregation of flex-objects while retaining flexibility. This paper further extends these approaches beyond flex-objects originating from energy consumption by additionally considering flex-objects originating from energy production...... 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...

  18. Flexible protection for metal bellows (United States)

    Kimble, K. G.


    RTV silicone is used with a braided wire sheath surrounding the metal bellows in fluid transfer systems. It demonstrated best overall performance in flexibility and shock absorbing tests, high temperature, low temperature, and salt spray.

  19. Flexibility as a Strategy in Nucleoside Antiviral Drug Design. (United States)

    Peters, H L; Ku, T C; Seley-Radtke, K L


    As far back as Melville Wolfrom's acyclic sugar synthesis in the 1960's, synthesis of flexible nucleoside analogues have been an area of interest. This concept, however, went against years of enzyme-substrate binding theory. Hence, acyclic methodology in antiviral drug design did not take off until the discovery and subsequent FDA approval of such analogues as Acyclovir and Tenofovir. More recently, the observation that flexible nucleosides could overcome drug resistance spawned a renewed interest in the field of nucleoside drug design. The next generation of flexible nucleosides shifted the focus from the sugar moiety to the nucleobase. With analogues such as Seley-Radtke "fleximers", and Herdewijn's C5 substituted 2'-deoxyuridines, the area of base flexibility has seen great expansion. More recently, the marriage of these methodologies with acyclic sugars has resulted in a series of acyclic flex-base nucleosides with a wide range of antiviral properties, including some of the first to exhibit anti-coronavirus activity. Various flexible nucleosides and their corresponding nucleobases will be compared in this review.

  20. Flexible solar-array mechanism (United States)

    Olson, M. C.


    One of the key elements of the flexible rolled-up solar array system is a mechanism to deploy, retract, and store the flexible solar-cell arrays. The selection of components, the design of the mechanism assembly, and the tests that were performed are discussed. During 6 months in orbit, all mission objectives were satisfied, and inflight performance has shown good correlation with preflight analyses and tests.

  1. Flexible packaging for PV modules (United States)

    Dhere, Neelkanth G.


    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/( under ambient conditions. In comparison, light emitting diodes employ packaging components that have WVTR of ~10-6 g/( 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.



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


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

  3. Oxide Heteroepitaxy for Flexible Optoelectronics. (United States)

    Bitla, Yugandhar; Chen, Ching; Lee, Hsien-Chang; Do, Thi Hien; Ma, Chun-Hao; Qui, Le Van; Huang, Chun-Wei; Wu, Wen-Wei; Chang, Li; Chiu, Po-Wen; Chu, Ying-Hao


    The emerging technological demands for flexible and transparent electronic devices have compelled researchers to look beyond the current silicon-based electronics. However, fabrication of devices on conventional flexible substrates with superior performance are constrained by the trade-off between processing temperature and device performance. Here, we propose an alternative strategy to circumvent this issue via the heteroepitaxial growth of transparent conducting oxides (TCO) on the flexible mica substrate with performance comparable to that of their rigid counterparts. With the examples of ITO and AZO as a case study, a strong emphasis is laid upon the growth of flexible yet epitaxial TCO relying muscovite's superior properties compared to those of conventional flexible substrates and its compatibility with the present fabrication methods. Besides excellent optoelectro-mechanical properties, an additional functionality of high-temperature stability, normally lacking in the current state-of-the-art transparent flexitronics, is provided by these heterostructures. These epitaxial TCO electrodes with good chemical and thermal stabilities as well as mechanical durability can significantly contribute to the field of flexible, light-weight, and portable smart electronics.

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

    Niknezhad, Zhila; Hassani, Leila; Norouzi, Davood


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

  5. Analyzing binding data. (United States)

    Motulsky, Harvey J; Neubig, Richard R


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

  6. Global Flexibility, synecdoche of progress

    Directory of Open Access Journals (Sweden)

    Clara Selva Olid


    Full Text Available The purpose of this article is to explore the flexibility, its uses, types and new concepts to address and empower the global flexibility as an integral tool to facilitate change, adapt to the environment in an advantageous manner and innovate. In times of economic, social, technological and global chances, like today, partners and organizations are claimed to increase their polyvalence and versatility, in order to move towards new organizational and dedication models. In this context and given the need to have a construct that broadly and inherently meets and baste transversely to the different stakeholders of the organization, its structures and forms and mediation between them emerges global flexibility. Despite the challenge of proposing and permeabilising a new construct, no less what it provides, as it is presented as a natural tool to empower wellbeing within organizational and social life.

  7. Studies Of Residual Flexibility And Vibration Testing (United States)

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


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

  8. Polymer electronics a flexible technology

    CERN Document Server

    Technology, Rapra


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

  9. Global Analysis of Flexible Risers

    DEFF Research Database (Denmark)

    Banke, Lars


    and thus resists the loading from the environment in a more suitable way.A flexible pipe is a composite structure, built up of several layers each having a specific function. Due to the flexibility, the response of the pipe in wave induced motions are governed by a complex hydroelastic set of differential...... parameters.The idea is to divide the riser system of riser and end fitting system into a global system including the riser and a local system of the bending stiffener and the end fitting. The forces at top of the riser shall be used as input for the design of the local system.This report introduces a non...

  10. Balancing energy flexibilities through aggregation

    DEFF Research Database (Denmark)

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


    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...

  11. Architecture of cognitive flexibility revealed by lesion mapping. (United States)

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


    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 R(2)=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.

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

  13. Protein flexibility in the light of structural alphabets

    Directory of Open Access Journals (Sweden)

    Pierrick eCraveur


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


    Directory of Open Access Journals (Sweden)

    Владимир Маркович Кенис


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

  15. Taming Time with Flexible Work. (United States)

    Stamps, David


    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)

  16. Functional flexibility and team performance

    NARCIS (Netherlands)

    Molleman, E.; Slomp, J.


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

  17. Flexible Bistable Cholesteric Reflective Displays (United States)

    Yang, Deng-Ke


    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.

  18. Drops spreading on flexible fibers (United States)

    Somszor, Katarzyna; Boulogne, François; Sauret, Alban; Dressaire, Emilie; Stone, Howard


    Fibrous media are encountered in many engineered systems such as textile, paper and insulating materials. In most of these materials, fibers are randomly oriented and form a complex network in which drops of wetting liquid tend to accumulate at the nodes of the network. Here we investigate the role of the fiber flexibility on the spreading of a small volume of liquid on a pair of crossed flexible fibers. A drop of silicone oil is dispensed at the point of contact of the fibers and we characterize the liquid morphologies as we vary the volume of liquid, the angle between the fibers, and the length and bending modulus of the fibers. Drop morphologies previously reported for rigid fibers, i.e. a drop, a column and a mixed morphology, are also observed on flexible fibers with modified domains of existence. Moreover, at small inclination angles of the fibers, a new behavior is observed: the fibers bend and collapse. Depending on the volume, the liquid can adopt a column or a mixed morphology on the collapsed fibers. We rationalize our observations with a model based on energetic considerations. Our study suggests that the fiber flexibility adds a rich variety of behaviors that can be crucial for industrial applications.

  19. Creep behaviour of flexible adhesives

    NARCIS (Netherlands)

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


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

  20. Easy and flexible mixture distributions

    DEFF Research Database (Denmark)

    Fosgerau, Mogens; Mabit, Stefan L.


    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...

  1. Super Spy variants implicate flexibility in chaperone action. (United States)

    Quan, Shu; Wang, Lili; Petrotchenko, Evgeniy V; Makepeace, Karl At; Horowitz, Scott; Yang, Jianyi; Zhang, Yang; Borchers, Christoph H; Bardwell, James Ca


    Experimental study of the role of disorder in protein function is challenging. It has been proposed that proteins utilize disordered regions in the adaptive recognition of their various binding partners. However apart from a few exceptions, defining the importance of disorder in promiscuous binding interactions has proven to be difficult. In this paper, we have utilized a genetic selection that links protein stability to antibiotic resistance to isolate variants of the newly discovered chaperone Spy that show an up to 7 fold improved chaperone activity against a variety of substrates. These "Super Spy" variants show tighter binding to client proteins and are generally more unstable than is wild type Spy and show increases in apparent flexibility. We establish a good relationship between the degree of their instability and the improvement they show in their chaperone activity. Our results provide evidence for the importance of disorder and flexibility in chaperone function. DOI:

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


    Paç, Mehmet Fazıl


    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...

  3. Docking validation resources: protein family and ligand flexibility experiments. (United States)

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


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

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

    Chakraborty, Sreeja; Bose, Madhuparna; Sarkar, Munna


    Drugs belonging to the Non-steroidal anti-inflammatory (NSAID) group are not only used as anti-inflammatory, analgesic and anti-pyretic agents, but also show anti-cancer effects. Complexing them with a bioactive metal like copper, show an enhancement in their anti-cancer effects compared to the bare drugs, whose exact mechanism of action is not yet fully understood. For the first time, it was shown by our group that Cu(II)-NSAIDs can directly bind to the DNA backbone. The ability of the copper complexes of NSAIDs namely meloxicam and piroxicam to bind to the DNA backbone could be a possible molecular mechanism behind their enhanced anticancer effects. Elucidating base sequence specific interaction of Cu(II)-NSAIDs to the DNA will provide information on their possible binding sites in the genome sequence. In this work, we present how these complexes respond to differences in structure and hydration pattern of GC rich sequences. For this, binding studies of Cu(II) complexes of piroxicam [Cu(II)-(Px)2 (L)2] and meloxicam [Cu(II)-(Mx)2 (L)] with alternating GC (polydG-dC) and homopolymeric GC (polydG-polydC) sequences were carried out using a combination of spectroscopic techniques that include UV-Vis absorption, fluorescence and circular dichroism (CD) spectroscopy. The Cu(II)-NSAIDs show strong binding affinity to both polydG-dC and polydG-polydC. The role reversal of Cu(II)-meloxicam from a strong binder of polydG-dC (Kb=11.5×10(3) M(-1)) to a weak binder of polydG-polydC (Kb=5.02×10(3) M(-1)), while Cu(II)-piroxicam changes from a strong binder of polydG-polydC (Kb=8.18×10(3) M(-1)) to a weak one of polydG-dC (Kb=2.18×10(3) M(-1)), point to the sensitivity of these complexes to changes in the backbone structures/hydration. Changes in the profiles of UV absorption band and CD difference spectra, upon complex binding to polynucleotides and the results of competitive binding assay using ethidium bromide (EtBr) fluorescence indicate different binding modes in each

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

    Chakraborty, Sreeja; Bose, Madhuparna; Sarkar, Munna


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

  6. Improved Evolutionary Hybrids for Flexible Ligand Docking in Autodock

    Energy Technology Data Exchange (ETDEWEB)

    Belew, R.K.; Hart, W.E.; Morris, G.M.; Rosin, C.


    In this paper we evaluate the design of the hybrid evolutionary algorithms (EAs) that are currently used to perform flexible ligand binding in the Autodock docking software. Hybrid EAs incorporate specialized operators that exploit domain-specific features to accelerate an EA's search. We consider hybrid EAs that use an integrated local search operator to reline individuals within each iteration of the search. We evaluate several factors that impact the efficacy of a hybrid EA, and we propose new hybrid EAs that provide more robust convergence to low-energy docking configurations than the methods currently available in Autodock.


    Directory of Open Access Journals (Sweden)

    TECULESCU Silviu Alexandru


    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.


    Energy Technology Data Exchange (ETDEWEB)

    DeScioli, Derek


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

  9. Exploiting protein intrinsic flexibility in drug design. (United States)

    Lukman, Suryani; Verma, Chandra S; Fuentes, Gloria


    Molecular recognition in biological systems relies on the existence of specific attractive interactions between two partner molecules. Structure-based drug design seeks to identify and optimize such interactions between ligands and their protein targets. The approach followed in medicinal chemistry follows a combination of careful analysis of structural data together with experimental and/or theoretical studies on the system. This chapter focuses on the fact that a protein is not fully characterized by a single structure, but by an ensemble of states, some of them represent "hidden conformations" with cryptic binding sites. We highlight case studies where both experimental and computational methods have been used to mutually drive each other in an attempt to improve the success of the drug design approaches.Advances in both experimental techniques and computational methods have greatly improved our physico-chemical understanding of the functional mechanisms in biomolecules and opened a debate about the interplay between molecular structure and biomolecular function. The beautiful static pictures of protein structures may have led to neglecting the intrinsic protein flexibility, however we are entering a new era where more sophisticated methods are used to exploit this ability of macromolecules, and this will definitely lead to the inclusion of the notion in the pharmaceutical field of drug design.

  10. Advanced solderless flexible thermal link (United States)

    Williams, Brian G.; Jensen, Scott M.; Batty, J. Clair


    Flexible thermal links play an important role int he thermal management of cryogenically cooled components. The purpose of these links is to provide a means of transferring heat from a cooled component to a cooler reservoir with little increase in temperature. The standard soldered approach although effective proves to be time consuming and contributes to added thermal impedances which degrade the performance of the link. For system with little tolerance for temperature differences between cooled components and a cooling source this is undesirable. The authors of this paper have developed a technique by which thin metal foil or braided wire can be attached to metal end blocks without any solder using the swaging process. Swaging provides a fast, simple method for providing a low thermal impedance between the foils and blocks. This paper describes the characteristics of these thermal links in terms of length, mass, thermal resistance, flexibility, and survivability.

  11. Flexible spintronic devices on Kapton

    DEFF Research Database (Denmark)

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


    of bending angle (r = 5 mm) have been achieved without degradation of the device performance, reaching room-temperature tunneling magnetoresistance ratios of 12% in bended Co/Al2O3/NiFe junctions. In addition, a suitable route to pattern high-quality nanostructures directly on the polyimide surface......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...... is established. These results demonstrate that Kapton is a promising platform for low-cost, flexible spintronic applications involving tunnel junction elements and nanostructurization. ...

  12. Lost and Found in Flexibility

    DEFF Research Database (Denmark)

    Bødker, Susanne; Christiansen, Ellen


    '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 l...... studies, the authors develop a requirements specification framework and a revised list of challenges for developers of Information Systems that support social awareness in 'New work'......., 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...

  13. Flexible Temperature Sensors on Fibers

    Directory of Open Access Journals (Sweden)

    Marcin Sloma


    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.

  14. Flexible Adaptation in Cognitive Radios

    CERN Document Server

    Li, Shujun


    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 ...

  15. Flexible Execution of Cognitive Procedures. (United States)


    Rosenbloom. P. (1988). Symbolic Architectures. In Posner, M. (Ed.), FoundatiCns of Cogniive Science . Cambridge. MKA MIT Press. In preparation. Nii. P. , 1986...Procedures 00 Technical Report PCG-5 14 Kurt VanLehn and William Ball Departments of Psychology and Computer Science Carnegie-Mellon University...Psychology and Computer Science Carnegie-Mellon University Pittsburgh, PA 15213 U.S.A 30 June 1987 Running head: Flexible Execution of Cognitive

  16. CRISIS FOCUS Uncertainty and Flexibility

    Institute of Scientific and Technical Information of China (English)


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

  17. Flexible Photonic Cellulose Nanocrystal Films


    Guidetti, G.; Atifi, S; Vignolini, S; Hamad, WY


    The fabrication of self-assembled cellulose nanocrystal (CNC) films of tunable photonic and mechanical properties using a facile, green approach is demonstrated. The combination of tunable flexibility and iridescence can dramatically expand CNC coating and film barrier capabilities for paints and coating applications, sustainable consumer packaging products, as well as effective templates for photonic and optoelectronic materials and structures. CelluForce Inc., Biotechnology and Biologica...

  18. Organisationsprinzipien zielgerichteter Bewegungen flexibler Greiforgane


    Martin, Franziska


    Flexible grasping organs like the trunk of elephants and the grasping tail of spider monkeys have to deal with a high degree of movement freedom in their goal-directed movements. The aim of this study was to find the basic organisation principles they apply in order to lower the coordination expense of their movements. Therefore, in hypothesis I a reduction of the degree of movement freedom was postulated whereas hypothesis II assumed a specialization of movements towards one side. Since trun...

  19. Flexible pile thermal barrier insulator (United States)

    Anderson, G. E.; Fell, D. M.; Tesinsky, J. S. (Inventor)


    A flexible pile thermal barrier insulator included a plurality of upstanding pile yarns. A generally planar backing section supported the upstanding pile yarns. The backing section included a plurality of filler yarns forming a mesh in a first direction. A plurality of warp yarns were looped around said filler yarns and pile yarns in the backing section and formed a mesh in a second direction. A binder prevented separation of the yarns in the backing section.

  20. The Flexibility of Ectopic Lipids

    Directory of Open Access Journals (Sweden)

    Hannah Loher


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

  1. Design of satellite flexibility experiments (United States)

    Kaplan, M. H.; Hillard, S. E.


    A preliminary study has been completed to begin development of a flight experiment to measure spacecraft control/flexible structure interaction. The work reported consists of two phases: identification of appropriate structural parameters which can be associated with flexibility phenomena, and suggestions for the development of an experiment for a satellite configuration typical of near-future vehicles which are sensitive to such effects. Recommendations are made with respect to the type of data to be collected and instrumentation associated with these data. The approach consists of developing the equations of motion for a vehicle possessing a flexible solar array, then linearizing about some nominal motion of the craft. A set of solutions are assumed for array deflection using a continuous normal mode method and important parameters are exposed. Inflight and ground based measurements are distinguished. Interrelationships between these parameters, measurement techniques, and input requirements are discussed which assure minimization of special vehicle maneuvers and optimization of data to be obtained during the normal flight sequence.

  2. Membrane binding domains


    Hurley, James H.


    Eukaryotic signaling and trafficking proteins are rich in modular domains that bind cell membranes. These binding events are tightly regulated in space and time. The structural, biochemical, and biophysical mechanisms for targeting have been worked out for many families of membrane binding domains. This review takes a comparative view of seven major classes of membrane binding domains, the C1, C2, PH, FYVE, PX, ENTH, and BAR domains. These domains use a combination of specific headgroup inter...

  3. Shaft-Guidance for Flexible Endoscopes

    NARCIS (Netherlands)

    Loeve, A.J.


    Flexible endoscopes (long, slender, flexible instruments with a camera and light at the distal end, having working channels to introduce flexible instruments) are used for diagnostic and therapeutic interventions inside the human digestive system and inside the abdomen. Though used for their flexibi

  4. Financial Flexibility in North Carolina Schools. (United States)

    Suarez, Tanya M.; Polen, Deborah A.

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

  5. Towards Measuring Investment in Flexible Foundry Manufacturing

    Directory of Open Access Journals (Sweden)

    Rhythm Suren Wadhwa


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

  6. Structure-Based Understanding of Binding Affinity and Mode of Estrogen Receptor α Agonists and Antagonists (United States)

    Barron, Mace G.


    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 interactions and specific hydrogen bonds with the ligand. Here we present a framework for quantitative analysis of the steric and electronic features of the human ERα-ligand complex using three dimensional (3D) protein-ligand interaction description combined with 3D-QSAR approach. An empirical hydrophobicity density field is applied to account for hydrophobic contacts of ligand within the LBP. The obtained 3D-QSAR model revealed that hydrophobic contacts primarily determine binding affinity and govern binding mode with hydrogen bonds. Several residues of the LBP appear to be quite flexible and adopt a spectrum of conformations in various ERα-ligand complexes, in particular His524. The 3D-QSAR was combined with molecular docking based on three receptor conformations to accommodate receptor flexibility. The model indicates that the dynamic character of the LBP allows accommodation and stable binding of structurally diverse ligands, and proper representation of the protein flexibility is critical for reasonable description of binding of the ligands. Our results provide a quantitative and mechanistic understanding of binding affinity and mode of ERα agonists and antagonists that may be applicable to other nuclear receptors. PMID:28061508

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

    Directory of Open Access Journals (Sweden)

    Kathryn A Loving


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

  8. Unravelling Mg2+-RNA binding with atomistic molecular dynamics. (United States)

    Cunha, Richard A; Bussi, Giovanni


    Interaction with divalent cations is of paramount importance for RNA structural stability and function. We here report a detailed molecular dynamics study of all the possible binding sites for Mg(2+) on a RNA duplex, including both direct (inner sphere) and indirect (outer sphere) binding. In order to tackle sampling issues, we develop a modified version of bias-exchange metadynamics which allows us to simultaneously compute affinities with previously unreported statistical accuracy. Results correctly reproduce trends observed in crystallographic databases. Based on this, we simulate a carefully chosen set of models that allows us to quantify the effects of competition with monovalent cations, RNA flexibility, and RNA hybridization. Our simulations reproduce the decrease and increase of Mg(2+) affinity due to ion competition and hybridization respectively, and predict that RNA flexibility has a site dependent effect. This suggests a non trivial interplay between RNA conformational entropy and divalent cation binding.

  9. Analyzing radioligand binding data. (United States)

    Motulsky, Harvey; Neubig, Richard


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

  10. Designing for Flexibility in the Traditional University

    Directory of Open Access Journals (Sweden)

    Betty Collis


    Full Text Available Instructors in traditional universities are expected to respond to the needs of an increasingly diverse student body by making more flexibility available in their courses. Based on a systematic analysis of flexibility options, various tools to help instructors in the design of their course Web environments for more flexibility have been built into the CMS (Course Management System used at the University of Twente since 1997. It is our experience that instructors use the tools to increase course flexibility with regard to the efficiency and logistics of participation but do relatively less with respect to increasing course flexibility when this involves new pedagogies.

  11. Increase in flexibility with latest technologies

    Energy Technology Data Exchange (ETDEWEB)

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


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

  12. Cognitive Flexibility in Obsessive Compulsive Disorder

    DEFF Research Database (Denmark)

    Jónsson, Hjalti; Salkovskis, Paul M.

    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. Flexible Envelope Request Notation (FERN) (United States)

    Zoch, David R.; Lavallee, David; Weinstein, Stuart


    The following topics are presented in view graph form and include the following: scheduling application; the motivation for the Flexible Envelope Request Notation (FERN); characteristics of FERN; types of information needed in requests; where information is stored in requests; FERN structures; generic requests; resource availability for pooled resources; expressive notation; temporal constraints; time formats; changes to FERN; sample FERN requests; the temporal relationship between two steps; maximum activity length to limit step delays; alternative requests; the temporal relationship between two activities; and idle resource usage between steps.

  14. Fully Integral, Flexible Composite Driveshaft (United States)

    Lawrie, Duncan


    An all-composite driveshaft incorporating integral flexible diaphragms was developed for prime contractor testing. This new approach makes obsolete the split lines required to attach metallic flex elements and either metallic or composite spacing tubes in current solutions. Subcritical driveshaft weights can be achieved that are half that of incumbent technology for typical rotary wing shaft lengths. Spacing tubes compose an integral part of the initial tooling but remain part of the finished shaft and control natural frequencies and torsional stability. A concurrently engineered manufacturing process and design for performance competes with incumbent solutions at significantly lower weight and with the probability of improved damage tolerance and fatigue life.

  15. Lifelong Open and Flexible Learning

    DEFF Research Database (Denmark)

    Bang, Jørgen


    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....

  16. Flexible high-speed CODEC (United States)

    Segallis, Greg P.; Wernlund, Jim V.; Corry, Glen


    This report is prepared by Harris Government Communication Systems Division for NASA Lewis Research Center under contract NAS3-25087. It is written in accordance with SOW section 4.0 (d) as detailed in section 2.6. The purpose of this document is to provide a summary of the program, performance results and analysis, and a technical assessment. The purpose of this program was to develop a flexible, high-speed CODEC that provides substantial coding gain while maintaining bandwidth efficiency for use in both continuous and bursted data environments for a variety of applications.

  17. Versatile Flexible Graphene Multielectrode Arrays. (United States)

    Kireev, Dmitry; Seyock, Silke; Ernst, Mathis; Maybeck, Vanessa; Wolfrum, Bernhard; Offenhäusser, Andreas


    Graphene is a promising material possessing features relevant to bioelectronics applications. Graphene microelectrodes (GMEAs), which are fabricated in a dense array on a flexible polyimide substrate, were investigated in this work for their performance via electrical impedance spectroscopy. Biocompatibility and suitability of the GMEAs for extracellular recordings were tested by measuring electrical activities from acute heart tissue and cardiac muscle cells. The recordings show encouraging signal-to-noise ratios of 65 ± 15 for heart tissue recordings and 20 ± 10 for HL-1 cells. Considering the low noise and excellent robustness of the devices, the sensor arrays are suitable for diverse and biologically relevant applications.

  18. Flexible experimental FPGA based platform

    DEFF Research Database (Denmark)

    Andersen, Karsten Holm; Nymand, Morten


    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...

  19. Ureaplasma urealyticum binds mannose-binding lectin. (United States)

    Benstein, Barbara D; Ourth, Donald D; Crouse, Dennis T; Shanklin, D Radford


    Mannose-binding C-type lectin (MBL) is an important component of innate immunity in mammals. Mannose-binding lectin (MBL), an acute phase protein, acts as an opsonin for phagocytosis and also activates the mannan-binding lectin complement pathway. It may play a particularly significant role during infancy before adequate specific protection can be provided by the adaptive immune system. Ureaplasma urealyticum has been linked to several diseases including pneumonia and chronic lung disease (CLD) in premature infants. We therefore investigated the ability of U. urealyticum to bind MBL. A guinea pig IgG anti-rabbit-MBL antiserum was produced. An immunoblot (dot-blot) assay done on nitrocellulose membrane determined that the anti-MBL antibody had specificity against both rabbit and human MBL. Pure cultures of U. urealyticum, serotype 3, were used to make slide preparations. The slides containing the organisms were then incubated with nonimmune rabbit serum containing MBL. Ureaplasma was shown to bind rabbit MBL with an immunocytochemical assay using the guinea pig IgG anti-rabbit MBL antiserum. Horseradish peroxidase (HRP)-labeled anti-guinea pig IgG was used to localize the reaction. The anti-MBL antiserum was also used in an immunocytochemical assay to localize U. urealyticum in histological sections of lungs from mice specifically infected with this organism. The same method also indicated binding of MBL by ureaplasma in human lung tissue obtained at autopsy from culture positive infants. Our results demonstrate that ureaplasma has the capacity to bind MBL. The absence of MBL may play a role in the predisposition of diseases related to this organism.

  20. Ligand binding mechanics of maltose binding protein. (United States)

    Bertz, Morten; Rief, Matthias


    In the past decade, single-molecule force spectroscopy has provided new insights into the key interactions stabilizing folded proteins. A few recent studies probing the effects of ligand binding on mechanical protein stability have come to quite different conclusions. While some proteins seem to be stabilized considerably by a bound ligand, others appear to be unaffected. Since force acts as a vector in space, it is conceivable that mechanical stabilization by ligand binding is dependent on the direction of force application. In this study, we vary the direction of the force to investigate the effect of ligand binding on the stability of maltose binding protein (MBP). MBP consists of two lobes connected by a hinge region that move from an open to a closed conformation when the ligand maltose binds. Previous mechanical experiments, where load was applied to the N and C termini, have demonstrated that MBP is built up of four building blocks (unfoldons) that sequentially detach from the folded structure. In this study, we design the pulling direction so that force application moves the two MBP lobes apart along the hinge axis. Mechanical unfolding in this geometry proceeds via an intermediate state whose boundaries coincide with previously reported MBP unfoldons. We find that in contrast to N-C-terminal pulling experiments, the mechanical stability of MBP is increased by ligand binding when load is applied to the two lobes and force breaks the protein-ligand interactions directly. Contour length measurements indicate that MBP is forced into an open conformation before unfolding even if ligand is bound. Using mutagenesis experiments, we demonstrate that the mechanical stabilization effect is due to only a few key interactions of the protein with its ligand. This work illustrates how varying the direction of the applied force allows revealing important details about the ligand binding mechanics of a large protein.

  1. Efficient algorithms to explore conformation spaces of flexible protein loops. (United States)

    Yao, Peggy; Dhanik, Ankur; Marz, Nathan; Propper, Ryan; Kou, Charles; Liu, Guanfeng; van den Bedem, Henry; Latombe, Jean-Claude; Halperin-Landsberg, Inbal; Altman, Russ Biagio


    Several applications in biology - e.g., incorporation of protein flexibility in ligand docking algorithms, interpretation of fuzzy X-ray crystallographic data, and homology modeling - require computing the internal parameters of a flexible fragment (usually, a loop) of a protein in order to connect its termini to the rest of the protein without causing any steric clash. One must often sample many such conformations in order to explore and adequately represent the conformational range of the studied loop. While sampling must be fast, it is made difficult by the fact that two conflicting constraints - kinematic closure and clash avoidance - must be satisfied concurrently. This paper describes two efficient and complementary sampling algorithms to explore the space of closed clash-free conformations of a flexible protein loop. The "seed sampling" algorithm samples broadly from this space, while the "deformation sampling" algorithm uses seed conformations as starting points to explore the conformation space around them at a finer grain. Computational results are presented for various loops ranging from 5 to 25 residues. More specific results also show that the combination of the sampling algorithms with a functional site prediction software (FEATURE) makes it possible to compute and recognize calcium-binding loop conformations. The sampling algorithms are implemented in a toolkit (LoopTK), which is available at

  2. Analysis of binding behavior between dynamic structures of a papain and the peptide consisting of 10 GLY residues (United States)

    Nishiyama, Katsuhiko


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

  3. Flexible nets: disorder and induced fit in the associations of p53 and 14-3-3 with their partners


    Uversky Vladimir N; Yang Mary Qu; Yang Jack Y; Meng Jingwei; Oldfield Christopher J; Dunker A Keith


    Abstract Background Proteins are involved in many interactions with other proteins leading to networks that regulate and control a wide variety of physiological processes. Some of these proteins, called hub proteins or hubs, bind to many different protein partners. Protein intrinsic disorder, via diversity arising from structural plasticity or flexibility, provide a means for hubs to associate with many partners (Dunker AK, Cortese MS, Romero P, Iakoucheva LM, Uversky VN: Flexible Nets: The r...

  4. Flexible thin film magnetoimpedance sensors

    Energy Technology Data Exchange (ETDEWEB)

    Kurlyandskaya, G.V., E-mail: [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)


    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.

  5. Wetting of flexible fibre arrays. (United States)

    Duprat, C; Protière, S; Beebe, A Y; Stone, H A


    Fibrous media are functional and versatile materials, as demonstrated by their ubiquity both in natural systems such as feathers and adhesive pads and in engineered systems from nanotextured surfaces to textile products, where they offer benefits in filtration, insulation, wetting and colouring. The elasticity and high aspect ratios of the fibres allow deformation under capillary forces, which cause mechanical damage, matting self-assembly or colour changes, with many industrial and ecological consequences. Attempts to understand these systems have mostly focused on the wetting of rigid fibres or on elastocapillary effects in planar geometries and on a fibre brush withdrawn from an infinite bath. Here we consider the frequently encountered case of a liquid drop deposited on a flexible fibre array and show that flexibility, fibre geometry and drop volume are the crucial parameters that are necessary to understand the various observations referred to above. We identify the conditions required for a drop to remain compact with minimal spreading or to cause a pair of elastic fibres to coalesce. We find that there is a critical volume of liquid, and, hence, a critical drop size, above which this coalescence does not occur. We also identify a drop size that maximizes liquid capture. For both wetting and deformation of the substrates, we present rules that are deduced from the geometric and material properties of the fibres and the volume of the drop. These ideas are applicable to a wide range of fibrous materials, as we illustrate with examples for feathers, beetle tarsi, sprays and microfabricated systems.

  6. Flexible network wireless transceiver and flexible network telemetry transceiver (United States)

    Brown, Kenneth D.


    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.

  7. Extracellular-regulated kinase 2 is activated by the enhancement of hinge flexibility. (United States)

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


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

  8. Python bindings for libcloudph++


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


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

  9. Relationship between conformational flexibility and chelate cooperativity. (United States)

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


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

  10. Python bindings for libcloudph++

    CERN Document Server

    Jarecka, Dorota; Del Vento, Davide


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

  11. DNS & Bind Cookbook

    CERN Document Server

    Liu, Cricket


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

  12. Strength, flexibility, and maturity in adolescent athletes. (United States)

    Pratt, M


    The relationship between lower-extremity strength and flexibility and maturational status as measured by Tanner staging (TS) was assessed in 84 male high school athletes. The sum of one-repetition maximum lifts for knee extension and flexion was determined and flexibility was measured with the American Alliance of Health, Physical Education, Recreation, and Dance sit-and-reach test. Chronologic age, body weight, and percent fat were also recorded. Strength and flexibility were compared for each maturational and chronologic age category. Maturational age was better correlated with strength and flexibility than was chronologic age. All correlations were significant. Multiple regression analysis demonstrated significant correlations of TS and age with strength and flexibility. Tanner staging had greater predictive value than age for strength and flexibility. After adjusting for age, the relationship between TS and strength remained significant.

  13. Simulation and analysis of flexibly jointed manipulators (United States)

    Murphy, Steve H.; Wen, John T.; Saridis, George M.


    Modeling, simulation, and analysis of robot manipulators with non-negligible joint flexibility are studied. A recursive Newton-Euler model of the flexibly jointed manipulator is developed with many advantages over the traditional Lagrange-Euler methods. The Newton-Euler approach leads to a method for the simulation of a flexibly jointed manipulator in which the number of computations grows linearly with the number of links. Additionally, any function for the flexibility between the motor and link may be used permitting the simulation of nonlinear effects, such as backlash, in a uniform manner for all joints. An analysis of the control problems for flexibly jointed manipulators is presented by converting the Newton-Euler model to a Lagrange-Euler form. The detailed structure available in the model is used to examine linearizing controllers and shows the dependency of the control on the choice of flexible model and structure of the manipulator.

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

  15. Flexible Working Time Arrangements in Bulgaria


    Beleva, Iskra


    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...

  16. Flexibility in 21st Century Power Systems

    Energy Technology Data Exchange (ETDEWEB)

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


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

  17. 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.

  18. Mundari as a flexible language

    DEFF Research Database (Denmark)

    Hengeveld, Kees; Rijkhoff, Jan


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

  19. Adhesion Transition of Flexible Filaments (United States)

    Evans, Arthur; Lauga, Eric


    As forays into fabrication and self-assembly venture to increasingly small length scales, the role of adhesion events between material elements of the system must be closely scrutinized. This area of study is typically dominated by investigations into capillary adhesion, but relatively recent interest in carbon nanotubes and biomimetic devices have spurred interest in intermolecular forces as another source of micro- and nano-scale adhesion. We present here a far-field model for ``dry'' adhesion. We consider a small number N of flexible beams interacting with each other via a typical Lennard-Jones 6-12 potential, and describe the behavior of the system as the ratio of bending rigidity to beam-beam attraction is reduced. Applications ranging from fibrillar systems to the comparatively stiff carbon nanotubes are discussed.

  20. Flexible fixation and fracture healing

    DEFF Research Database (Denmark)

    Schmal, Hagen; Strohm, Peter C; Jaeger, Martin


    , noncomminuted fractures. External fixation uses external bars for stabilization, whereas internal fixation is realized by subcutaneous placement of locking plates. Both of these "biologic" osteosynthesis methods allow a minimally invasive approach and do not compromise fracture hematoma and periosteal blood...... of articular fractures. They allow for subchondral stabilization using small-diameter angular stable screws as well as buttressing of the joint and the metaphyseal component of a fracture. Biomechanically, they can be far stiffer than external fixators, because subcutaneous plates are located much closer...... to the bone surface than external fixator bars. External fixators have the advantage of being less expensive, highly flexible, and technically less demanding. They remain an integral part of orthopaedic surgery for emergent stabilization, for pediatric fractures, for definitive osteosynthesis in certain...


    DEFF Research Database (Denmark)

    Olsen, Ib Steen; Bonke, Sten


    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...... Ministry of Housing, 1984,1) During spring 2011 DTU Management at The Technical University of Denmark has initiated an evaluation with the aim of showing how the ideas from the original competition have been applied during the 25 years period. Thus this paper will review the above governmental policy...

  2. Alignment of flexible protein structures. (United States)

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


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

  3. Flexible Query Answering Systems 2006

    DEFF Research Database (Denmark)

    -classical Logics, Computational Linguistics and Natural Language Processing, Multimedia Information Systems, and Human--Computer Interaction, including reports of interesting applications. We wish to thank the contributors for their excellent papers and the referees, publisher, and sponsors for their effort......, and intuitive access to information for every type of need. This multidisciplinary conference draws on several research areas, including information retrieval, database management, information filtering, knowledge representation, soft computing, management of multimedia information, and human-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...

  4. Interpretive Flexibility in Mobile Health:

    DEFF Research Database (Denmark)

    Agger Nielsen, Jeppe; Mathiassen, Lars


    Background: Mobile technologies have emerged as important tools that health care personnel can use to gain easy access to client data anywhere. This is particularly useful for nurses and care workers in home health care as they provide services to clients in many different settings. Although...... a growing body of evidence supports the use of mobile technologies, the diverse implications of mobile health have yet to be fully documented. Objective: Our objective was to examine a large-scale government-sponsored mobile health implementation program in the Danish home care sector and to understand how......-sponsored program, mobile technology proved to have considerable interpretive flexibility with variation in perceived nature of technology, technology strategy, and technology use between agencies. What was first seen as a very promising innovation across the Danish home care sector subsequently became the topic...

  5. Technology modernization assessment flexible automation

    Energy Technology Data Exchange (ETDEWEB)

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


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

  6. Material challenge for flexible organic devices

    Directory of Open Access Journals (Sweden)

    Jay Lewis


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

  7. High Performance Electronics on Flexible Silicon

    KAUST Repository

    Sevilla, Galo T.


    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.

  8. 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;


    (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...

  9. On Binding Domains

    NARCIS (Netherlands)

    Everaert, M.B.H.


    In this paper I want to explore reasons for replacing Binding Theory based on the anaphor-pronoun dichotomy by a Binding Theory allowing more domains restricting/defining anaphoric dependencies. This will, thus, have consequences for the partitioning of anaphoric elements, presupposing more types of

  10. Melanin-binding radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

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


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

  11. DNS BIND Server Configuration

    Directory of Open Access Journals (Sweden)

    Radu MARSANU


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

  12. Thermodynamics of fragment binding. (United States)

    Ferenczy, György G; Keserű, György M


    The ligand binding pockets of proteins have preponderance of hydrophobic amino acids and are typically within the apolar interior of the protein; nevertheless, they are able to bind low complexity, polar, water-soluble fragments. In order to understand this phenomenon, we analyzed high resolution X-ray data of protein-ligand complexes from the Protein Data Bank and found that fragments bind to proteins with two near optimal geometry H-bonds on average. The linear extent of the fragment binding site was found not to be larger than 10 Å, and the H-bonding region was found to be restricted to about 5 Å on average. The number of conserved H-bonds in proteins cocrystallized with multiple different fragments is also near to 2. These fragment binding sites that are able to form limited number of strong H-bonds in a hydrophobic environment are identified as hot spots. An estimate of the free-energy gain of H-bond formation versus apolar desolvation supports that fragment sized compounds need H-bonds to achieve detectable binding. This suggests that fragment binding is mostly enthalpic that is in line with their observed binding thermodynamics documented in Isothermal Titration Calorimetry (ITC) data sets and gives a thermodynamic rationale for fragment based approaches. The binding of larger compounds tends to more rely on apolar desolvation with a corresponding increase of the entropy content of their binding free-energy. These findings explain the reported size-dependence of maximal available affinity and ligand efficiency both behaving differently in the small molecule region featured by strong H-bond formation and in the larger molecule region featured by apolar desolvation.

  13. A fast flexible docking method using an incremental construction algorithm. (United States)

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


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

  14. Structural Dynamics of the Cereblon Ligand Binding Domain (United States)

    Hartmann, Marcus D.; Boichenko, Iuliia; Coles, Murray; Lupas, Andrei N.; Hernandez Alvarez, Birte


    Cereblon, a primary target of thalidomide and its derivatives, has been characterized structurally from both bacteria and animals. Especially well studied is the thalidomide binding domain, CULT, which shows an invariable structure across different organisms and in complex with different ligands. Here, based on a series of crystal structures of a bacterial representative, we reveal the conformational flexibility and structural dynamics of this domain. In particular, we follow the unfolding of large fractions of the domain upon release of thalidomide in the crystalline state. Our results imply that a third of the domain, including the thalidomide binding pocket, only folds upon ligand binding. We further characterize the structural effect of the C-terminal truncation resulting from the mental-retardation linked R419X nonsense mutation in vitro and offer a mechanistic hypothesis for its irresponsiveness to thalidomide. At 1.2Å resolution, our data provide a view of thalidomide binding at atomic resolution. PMID:26024445

  15. Structural dynamics of the cereblon ligand binding domain.

    Directory of Open Access Journals (Sweden)

    Marcus D Hartmann

    Full Text Available Cereblon, a primary target of thalidomide and its derivatives, has been characterized structurally from both bacteria and animals. Especially well studied is the thalidomide binding domain, CULT, which shows an invariable structure across different organisms and in complex with different ligands. Here, based on a series of crystal structures of a bacterial representative, we reveal the conformational flexibility and structural dynamics of this domain. In particular, we follow the unfolding of large fractions of the domain upon release of thalidomide in the crystalline state. Our results imply that a third of the domain, including the thalidomide binding pocket, only folds upon ligand binding. We further characterize the structural effect of the C-terminal truncation resulting from the mental-retardation linked R419X nonsense mutation in vitro and offer a mechanistic hypothesis for its irresponsiveness to thalidomide. At 1.2Å resolution, our data provide a view of thalidomide binding at atomic resolution.

  16. Towards automated visual flexible endoscope navigation

    NARCIS (Netherlands)

    Stap, van der N.; Heijden, van der F.; Broeders, I.A.M.J.


    Background: 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

  17. New business model of flexible housing

    NARCIS (Netherlands)

    Zairul, Z.; Geraedts, R.P.


    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. Howeve

  18. 76 FR 40208 - Regulatory Flexibility Agenda (United States)


    ... Comment Period End 04/04/05 Next Action Undetermined ......... Regulatory Flexibility Analysis Required... FR 10521 NPRM Comment Period End 04/04/05 Next Action Undetermined ......... Regulatory Flexibility... 70 FR 10521 NPRM Comment Period End 04/04/05 Next Action Undetermined ............

  19. Demand flexibility from residential heat pump

    DEFF Research Database (Denmark)

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


    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...

  20. Supermarket Defrost Cycles As Flexible Reserve

    DEFF Research Database (Denmark)

    Pedersen, Rasmus; Sloth, Christoffer; Wisniewski, Rafal


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

  1. Quality and workflow integration in flexible manufacturing

    NARCIS (Netherlands)

    Dam, ten D.C.


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

  2. Scheduling parameters in flexible manufacturing cells

    NARCIS (Netherlands)

    Slomp, J.; Gaalman, G.J.C.; Ahmad, M.M.; Sullivan, W.G.; Migliore, H.; Randhawa, S.


    The existence of a well-designed scheduling procedure is a major condition for an effective integration of a flexible manufacturing cell (FMC) in the material flow of a firm. This paper shows the presence and relative importance of three parameter types in the scheduling of operations on a flexible

  3. Alternative lithography strategies for flexible electronics

    NARCIS (Netherlands)

    Moonen, P.


    Main aim of the research has been the development of alternative lithography strategies for the fabrication of complex, flexible electronic devices. Flexible bottom-contact, bottom-gate thin-film transistors were solely patterned with UV nanoimprint lithography on poly(ethylene naphthalate) foil. Pa

  4. Role of Flexibility in Sustainable Port Development

    NARCIS (Netherlands)

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


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

  5. Studies of a flexible heliac configuration

    Energy Technology Data Exchange (ETDEWEB)

    Hender, T.C.; Cantrell, J.L.; Harris, J.H.; Carreras, B.A.; Lynch, V.E.; Lyon, J.F.; Fabregas, J.A.; Guasp, J.; Lopez-Fraguas, A.; Navarro, A.P.


    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.

  6. Semiconductor films on flexible iridium substrates (United States)

    Goyal, Amit


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

  7. Designing Flexible Software for the "Electronic Board." (United States)

    Hativa, Nira


    Argues that software for electronic boards should address a variety of teaching styles, student abilities and ages, class textbooks, teaching objectives, and learning environments for flexibility of use. The software features that contribute to flexibility include frequent stops, options for going backwards, inter- and intra-unit jumps, and…

  8. Flexible Learning in an Information Society (United States)

    Khan, Badrul, Ed.


    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. Magnetoelectric Nanocomposites for Flexible Electronics

    KAUST Repository

    Al-Nassar, Mohammed Y.


    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

  10. Cloud flexibility using DIRAC interware (United States)

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


    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

  11. Harnessing Flexibility from Hot and Cold

    DEFF Research Database (Denmark)

    Kiviluoma, Juha; Heinen, Steve; Qazi, Hassan


    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......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 implemented as inflexible loads. This demand could also be made more flexible, but it comes with a cost. The main issue is to identify the cases in which the benefits will outweigh those costs, a matter that will naturally depend on the evolution of specific energy systems. In this article, we lay out some...

  12. Flexible Ultrasonic Phased-Array Probe

    Institute of Scientific and Technical Information of China (English)

    施克仁; 阙开良; 郭大勇


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

  13. Predicting bioactive conformations and binding modes of macrocycles (United States)

    Anighoro, Andrew; de la Vega de León, Antonio; Bajorath, Jürgen


    Macrocyclic compounds experience increasing interest in drug discovery. It is often thought that these large and chemically complex molecules provide promising candidates to address difficult targets and interfere with protein-protein interactions. From a computational viewpoint, these molecules are difficult to treat. For example, flexible docking of macrocyclic compounds is hindered by the limited ability of current docking approaches to optimize conformations of extended ring systems for pose prediction. Herein, we report predictions of bioactive conformations of macrocycles using conformational search and binding modes using docking. Conformational ensembles generated using specialized search technique of about 70 % of the tested macrocycles contained accurate bioactive conformations. However, these conformations were difficult to identify on the basis of conformational energies. Moreover, docking calculations with limited ligand flexibility starting from individual low energy conformations rarely yielded highly accurate binding modes. In about 40 % of the test cases, binding modes were approximated with reasonable accuracy. However, when conformational ensembles were subjected to rigid body docking, an increase in meaningful binding mode predictions to more than 50 % of the test cases was observed. Electrostatic effects did not contribute to these predictions in a positive or negative manner. Rather, achieving shape complementarity at macrocycle-target interfaces was a decisive factor. In summary, a combined computational protocol using pre-computed conformational ensembles of macrocycles as a starting point for docking shows promise in modeling binding modes of macrocyclic compounds.

  14. Experimental strategies for studying transcription factor-DNA binding specificities. (United States)

    Geertz, Marcel; Maerkl, Sebastian J


    Specific binding of transcription factors (TFs) determines in a large part the connectivity of gene regulatory networks as well as the quantitative level of gene expression. A multiplicity of both experimental and computational methods is currently used to discover and characterize the underlying TF-DNA interactions. Experimental methods can be further subdivided into in vitro- and in vivo-based approaches, each accenting different aspects of TF-binding events. In this review we summarize the flexibility and performance of a selection of both types of experimental methods. In conclusion, we argue that a serial combination of methods with different throughput and data type constitutes an optimal experimental strategy.

  15. GROMACS: fast, flexible, and free. (United States)

    Van Der Spoel, David; Lindahl, Erik; Hess, Berk; Groenhof, Gerrit; Mark, Alan E; Berendsen, Herman J C


    This article describes the software suite GROMACS (Groningen MAchine for Chemical Simulation) that was developed at the University of Groningen, The Netherlands, in the early 1990s. The software, written in ANSI C, originates from a parallel hardware project, and is well suited for parallelization on processor clusters. By careful optimization of neighbor searching and of inner loop performance, GROMACS is a very fast program for molecular dynamics simulation. It does not have a force field of its own, but is compatible with GROMOS, OPLS, AMBER, and ENCAD force fields. In addition, it can handle polarizable shell models and flexible constraints. The program is versatile, as force routines can be added by the user, tabulated functions can be specified, and analyses can be easily customized. Nonequilibrium dynamics and free energy determinations are incorporated. Interfaces with popular quantum-chemical packages (MOPAC, GAMES-UK, GAUSSIAN) are provided to perform mixed MM/QM simulations. The package includes about 100 utility and analysis programs. GROMACS is in the public domain and distributed (with source code and documentation) under the GNU General Public License. It is maintained by a group of developers from the Universities of Groningen, Uppsala, and Stockholm, and the Max Planck Institute for Polymer Research in Mainz. Its Web site is

  16. Mundari as a flexible language

    DEFF Research Database (Denmark)

    Hengeveld, Kees; Rijkhoff, Jan


    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......In this paper we intend to show that Mundari is one of the languages without distinct classes of verbs and nouns as far as its basic, non-derived vocabulary is concerned. Our contribution is organized as follows. Section 2 briefly presents a typology of parts-of-speech (PoS) systems, followed...... and verbs), thus disputing E&O’s claim that Mundari has clearly definable classes of verbs and nouns. The last section is concerned with a set of grammatical features which correlate with the presence of flexible lexemes in a language. It is concluded that Mundari displays all of the predicted features...

  17. Molecular mechanism of serotonin transporter inhibition elucidated by a new flexible docking protocol. (United States)

    Gabrielsen, Mari; Kurczab, Rafał; Ravna, Aina W; Kufareva, Irina; Abagyan, Ruben; Chilmonczyk, Zdzisław; Bojarski, Andrzej J; Sylte, Ingebrigt


    The two main groups of antidepressant drugs, the tricyclic antidepressants (TCAs) and the selective serotonin reuptake inhibitors (SSRIs), as well as several other compounds, act by inhibiting the serotonin transporter (SERT). However, the binding mode and molecular mechanism of inhibition in SERT are not fully understood. In this study, five classes of SERT inhibitors were docked into an outward-facing SERT homology model using a new 4D ensemble docking protocol. Unlike other docking protocols, where protein flexibility is not considered or is highly dependent on the ligand structure, flexibility was here obtained by side chain sampling of the amino acids of the binding pocket using biased probability Monte Carlo (BPMC) prior to docking. This resulted in the generation of multiple binding pocket conformations that the ligands were docked into. The docking results showed that the inhibitors were stacked between the aromatic amino acids of the extracellular gate (Y176, F335) presumably preventing its closure. The inhibitors interacted with amino acids in both the putative substrate binding site and more extracellular regions of the protein. A general structure-docking-based pharmacophore model was generated to explain binding of all studied classes of SERT inhibitors. Docking of a test set of actives and decoys furthermore showed that the outward-facing ensemble SERT homology model consistently and selectively scored the majority of active compounds above decoys, which indicates its usefulness in virtual screening.

  18. Flexibility and explicit solvent in molecular-dynamics-based docking of protein-glycosaminoglycan systems. (United States)

    Samsonov, Sergey A; Gehrcke, Jan-Philip; Pisabarro, M Teresa


    We present Dynamic Molecular Docking (DMD), a novel targeted molecular dynamics-based protocol developed to address ligand and receptor flexibility as well as the inclusion of explicit solvent in local molecular docking. A class of ligands for which docking performance especially benefits from overcoming these challenges is the glycosaminoglycans (GAGs). GAGs are periodic, highly flexible, and negatively charged polysaccharides playing an important role in the extracellular matrix via interaction with proteins such as growth factors and chemokines. The goal of our work has been to develop a proof of concept for an MD-based docking approach and to analyze its applicability for protein-GAG systems. DMD exploits the electrostatics-driven attraction of a ligand to its receptor, treats both as entirely flexible, and considers solvent explicitly. We show that DMD has high predictive significance for systems dominated by electrostatic attraction and demonstrate its capability to reliably identify the receptor residues contributing most to binding.

  19. 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.

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

    DEFF Research Database (Denmark)

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


    A study of the anion-binding properties of three structurally related lanthanide complexes, which all contain chemically identical anion-binding motifs, has revealed dramatic differences in their anion affinity. These arise as a consequence of changes in the substitution pattern on the periphery...... conformational space. Peripheral modifications to a binuclear lanthanide motif derived from α,α'-bis(DO3 Ayl)-m-xylene are shown to result in dramatic changes to the binding constant for isophthalate. In this system, the parent compound displays considerable conformational flexibility, yet can be assumed to bind...

  1. STARD4 Membrane Interactions and Sterol Binding. (United States)

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


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

  2. SHBG (Sex Hormone Binding Globulin) (United States)

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

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


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


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

  4. Probabilistic Model to Treat Flexibility in Molecular Contacts

    CERN Document Server

    Hakulinen, Riku


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

  5. Flexible Learning in an Information Society

    Directory of Open Access Journals (Sweden)

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


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

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

    Institute of Scientific and Technical Information of China (English)

    Qi Jian-Xun; Jiang Fan


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

  7. Implementation of Flexible Access System (United States)

    Wu, Chen-Hsiang; Peng, Jan-Wen; Shao, Shou-Kuo; Chen, Tzooming E.; Chen, Shih Chang; Lee, Meng-Shu; Yen, K.-Y.; Chen, Tsung-Mao; Wang, Ching Sheu; Tu, Yuan-Kuang


    In this paper we present the architecture, operation, and the implementation of a prototype system, flexible access system (FAS), developed by CHT T.L. for FITL applications. FAS adopts fiber to the curb (FTTC) topology and provides POTS, ISDN BRA, and T1 services. The system consists of three main parts, namely, fiber central office terminal (FCOT) at switch side, fiber nodes (FN) at customer side, and a monitor station. FCOT and FNs are connected through an STM-1 fiber distribution ring. The hardware structure and the operation principle for each module are described. FAS contains the mux-demux module, POTS, ISDN, and T1 central office/customer service modules, operation modules, and power module. In the design, each central office service module in FCOT simulates as a CPE to terminate signals from switch, and will separate the data and signaling and map them into DS1 format. Mux/demux module will add/drop these DS1, put the operation information in data communication channel (DCC), and convert them to STM-1 optical link. Each customer service module in FN simulates switch line cart to regenerate the signal for customers. The prototype system implementation confirms the benefits of introducing SDH add/drop technologies to FITL system to provide basic telecommunication services. The design experience reveals that the clock synchronization method and noise reduction technique can significantly influence the performance in such a system. The test results that demonstrate and verify the designed functionality and the service quality of the prototype system will be presented.

  8. Flexible Molybdenum Electrodes towards Designing Affinity Based Protein Biosensors. (United States)

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


    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.

  9. Probabilistic Quantification of Potentially Flexible Residential Demand

    DEFF Research Database (Denmark)

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


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

  10. Damping Properties of Flexible Epoxy Resin

    Institute of Scientific and Technical Information of China (English)

    WANG Xiang; LIU Hanxing; OUYANG Shixi


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

  11. Flexible Personnel Scheduling in the Parallel Environment

    Institute of Scientific and Technical Information of China (English)

    XU Ben-zhu; ZHANG Xing-ling


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

  12. Rigidity and flexibility of biological networks

    CERN Document Server

    Gaspar, Merse E


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

  13. Business Models for Power System Flexibility

    DEFF Research Database (Denmark)

    Boscan, Luis; Poudineh, Rahmatallah


    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......-enabling business models, adding new activities to the existing supply chain. Ranging from technological to market-based innovation, this chapter reviews the latest developments in these emerging models. The main conclusion is that when flexibility becomes scarce in the system, new players with their innovative...

  14. Flexibility-enabling Contracts in Electricity Markets

    DEFF Research Database (Denmark)

    Boscan, Luis; Poudineh, Rahmatallah

    . 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...

  15. Flexible flatfoot in children and adolescents


    Mosca, Vincent S.


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

  16. Exchange Rate Policy and Endogenous Price Flexibility


    Devereux, Michael B.


    A fixed exchange rate limits the ability of the real exchange rate to adjust to shocks, and tends to raise the volatility of real GDP. But adjustment may be enhanced if internal prices are more flexible under a fixed exchange rate. This Paper develops a model in which price setters incur a cost to retain the option of ex-post price flexibility. The benefit of flexibility is increasing in the variance of demand facing price-setters. We ask whether fixing the exchange rate is likely to increase...


    DEFF Research Database (Denmark)


    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....

  18. Dissecting the Binding Mode of Low Affinity Phage Display Peptide Ligands to Protein Targets by Hydrogen/Deuterium Exchange Coupled to Mass Spectrometry

    DEFF Research Database (Denmark)

    Leurs, Ulrike; Lohse, Brian; Ming, Shonoi A;


    Phage display (PD) is frequently used to discover peptides capable of binding to biological protein targets. The structural characterization of peptide-protein complexes is often challenging due to their low binding affinities and high structural flexibility. Here, we investigate the use of hydro......Phage display (PD) is frequently used to discover peptides capable of binding to biological protein targets. The structural characterization of peptide-protein complexes is often challenging due to their low binding affinities and high structural flexibility. Here, we investigate the use...

  19. Strain Monitoring of Flexible Structures (United States)

    Litteken, Douglas A.


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

  20. Topology optimization with flexible void area

    DEFF Research Database (Denmark)

    Clausen, Anders; Aage, Niels; Sigmund, Ole


    This paper presents a methodology for including fixed-area flexible void domains into the minimum compliance topology optimization problem. As opposed to the standard passive elements approach of rigidly specifying void areas within the design domain, the suggested approach allows these areas...... to be flexibly reshaped and repositioned subject to penalization on their moments of inertia, the positions of their centers of mass, and their shapes. The flexible void areas are introduced through a second, discrete design variable field, using the same discretization as the standard field of continuous...... density variables. The formulation is based on a combined approach: The primary sub-problem is to minimize compliance, subject to a volume constraint, with a secondary sub-problem of minimizing the disturbance from the flexible void areas. The design update is performed iteratively between the two...

  1. Flexible HVAC System for Lab or Classroom. (United States)

    Friedan, Jonathan


    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)

  2. Fully Integral, Flexible Composite Driveshaft Project (United States)

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

  3. Thin Flexible IMM Solar Array Project (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...

  4. Carbon Nanotube Flexible and Stretchable Electronics (United States)

    Cai, Le; Wang, Chuan


    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.

  5. Multisensory integration : flexible use of general operations

    NARCIS (Netherlands)

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


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

  6. Thin Flexible IMM Solar Array Project (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....

  7. On semiflexible, flexible and pie algebras

    CERN Document Server

    Bourke, John


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

  8. Graphene-Based Flexible and Stretchable Electronics. (United States)

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


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

  9. Carbon Nanotube Flexible and Stretchable Electronics. (United States)

    Cai, Le; Wang, Chuan


    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.

  10. IEA EBC Annex 67 Energy Flexible Buildings

    DEFF Research Database (Denmark)

    Marszal, Anna Joanna; Jensen, Søren Østergaard


    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...... and load control and thereby demand response based on the requirements of the surrounding grids. Currently there is, however, no overview or insight into how much Energy Flexibility different building types and their usage may be able to offer to future energy systems. Three is thus a need for increasing...

  11. On Quantification of Flexibility in Power Systems

    DEFF Research Database (Denmark)

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


    Large scale integration of fluctuating and nondispatchablegeneration and variable transmission patterns inducehigh uncertainty in power system operation. In turn,transmission system operators (TSOs) need explicit informationabout available flexibility to maintain a desired reliability level ata r...

  12. Piezoelectric RL shunt damping of flexible structures

    DEFF Research Database (Denmark)

    Høgsberg, Jan Becker; Krenk, Steen


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

  13. Methamphetamine Alters Brain Structures, Impairs Mental Flexibility (United States)

    ... after the methamphetamine exposure, and obtained magnetic resonance images (MRI) of the brain before and after the exposure. Figure 1. Reversal Trial Studies the Impact of Methamphetamine on Monkeys’ Mental Flexibility The trial evaluates an animal’s mental ...

  14. Resonant Electromagnetic Shunt Damping of Flexible Structures

    DEFF Research Database (Denmark)

    Høgsberg, Jan Becker


    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...

  15. Fully Integral, Flexible Composite Driveshaft Project (United States)

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

  16. Sources of Operational Flexibility, Greening the Grid

    Energy Technology Data Exchange (ETDEWEB)

    Katz, Jessica; Milligan, Michael; Cochran, Jaquelin


    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.

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

    Institute of Scientific and Technical Information of China (English)

    SU Xuanliang; CHENG Guoping; WANG Mingquan


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

  18. Enabling Technologies for Fabrication of Large Area Flexible Antennas Project (United States)

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

  19. Flexibility decline contributes to similarity of past and future thinking in Alzheimer's disease. (United States)

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


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

  20. Flexible joints in structural and multibody dynamics


    O. A. Bauchau; Han, S.


    Flexible joints, sometimes called bushing elements or force elements, are found in all structural and multibody dynamics codes. In their simplest form, flexible joints simply consist of sets of three linear and three torsional springs placed between two nodes of the model. For infinitesimal deformations, the selection of the lumped spring constants is an easy task, which can be based on a numerical simulation of the joint or on experimental measurements. If the joint undergoes finite deformat...

  1. Electrorheological fluid-actuated flexible platform (United States)

    Liu, Liyu; Niu, Xize; Wen, Weijia; Sheng, Ping


    The design, fabrication, and performance of an electrorheological (ER) fluid-actuated flexible platform integrated on a microfluidic chip are reported in this letter. The digitally regulated ER microvalves control the four diaphragms on which a platform is sustained. With electrical input signals, the platform can perform vibrations at tunable frequencies as well as generate complex leveling modes. The flexible platform can potentially act as a microdamper when its inputs are generated from a sensor, in combination with a feedback control system.

  2. Technical Design of Flexible Sustainable Energy Systems

    DEFF Research Database (Denmark)

    Lund, Henrik


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

  3. Simulating Flexible-Spacecraft Dynamics and Control (United States)

    Fedor, Joseph


    Versatile program applies to many types of spacecraft and dynamical problems. Flexible Spacecraft Dynamics and Control program (FSD) developed to aid in simulation of large class of flexible and rigid spacecraft. Extremely versatile and used in attitude dynamics and control analysis as well as in-orbit support of deployment and control of spacecraft. Applicable to inertially oriented spinning, Earth-oriented, or gravity-gradient-stabilized spacecraft. Written in FORTRAN 77.

  4. Regulation of flexible arms under gravity

    Energy Technology Data Exchange (ETDEWEB)

    De Luca, A. [Univ. di Roma, Rome (Italy). Dipt. di Informatica e Sistemistica; Siciliano, B. [Univ. di Napoli Federico, Napoli (Italy). Dipt. di Informatica e Sistemistica


    A simple controller is presented for the regulation problem of robot arms with flexible links under gravity. It consists of a joint PD feedback plus a constant feedforward. Global asymptotic stability of the reference equilibrium state is shown under a structural assumption about link elasticity and a mild condition on the proportional gain. The result holds also in the absence of internal damping of the flexible arm. A numerical case study is presented.

  5. Spacecraft Dynamic Characteristics While Deploying Flexible Beams

    Institute of Scientific and Technical Information of China (English)

    程绪铎; 李俊峰; 樊勇; 王照林


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

  6. Flexible receiver adapter formal design review

    Energy Technology Data Exchange (ETDEWEB)

    Krieg, S.A.


    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.

  7. Ageing characterization of exhaust flexible couplings



    The aim of this work is to investigate the mechanical strength of automotive exhaust flexible couplings subjected to thermo-mechanical fatigue and corrosion. Five different types of flexible coupling have been considered, realised by four different king of materials: three stainless steels (AISI 309, AISI 321, AISI 321 Ti) and a nickel alloy (Incoloy 825). These components have been tested by a dedicated procedure consisting of different cycles of fatigue, heating and corrosion. Performances ...

  8. 21 CFR 874.4710 - Esophagoscope (flexible or rigid) and accessories. (United States)


    ... generic type of device includes the flexible foreign body claw, flexible biopsy forceps, rigid biopsy curette, flexible biopsy brush, rigid biopsy forceps and flexible biopsy curette, but excludes...

  9. Fast Flexible Transistors with a Nanotrench Structure (United States)

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


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

  10. Fast Flexible Transistors with a Nanotrench Structure. (United States)

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


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

  11. Flexible Thermoelectric Generators on Silicon Fabric

    KAUST Repository

    Sevilla, Galo T.


    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.

  12. Functional flexibility in wild bonobo vocal behaviour

    Directory of Open Access Journals (Sweden)

    Zanna Clay


    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.

  13. Binding-site assessment by virtual fragment screening.

    Directory of Open Access Journals (Sweden)

    Niu Huang

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

  14. Statistical analysis of structural determinants for protein-DNA-binding specificity. (United States)

    Corona, Rosario I; Guo, Jun-Tao


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

  15. The conformational flexibility of the antibiotic virginiamycin M(1). (United States)

    Dang, Jason; Metzger, Robert P; Brownlee, Robert T C; Ng, Chai Ann; Bergdahl, Mikael; Separovic, Frances


    The antibiotic virginiamycin is a combination of two molecules, virginiamycin M(1) (VM1) and virginiamycin S(1) (VS1) or analogues, which function synergistically by binding to bacterial ribosomes and inhibiting bacterial protein synthesis. Both VM1 and VS1 dissolve poorly in water and are soluble in more hydrophobic solvents. We have recently reported that the 3D conformation of VM1 in CDCl(3) solution differs markedly from the conformation bound to a VM1 binding enzyme and to 50S ribosomes as found by X-ray crystallographic studies. We now report the results of further NMR studies and subsequent molecular modeling of VM1 dissolved in CD(3)CN/H(2)O and compare the structure with that in CD(3)OD and CDCl(3). The conformations of VM1 in CD(3)CN/H(2)O, CD(3)OD and CDCl(3) differ substantially from one another and from the bound form, with the aqueous form most like the bound structure. We propose that the flexibility of the VM1 molecule in response to environmental conditions contributes to its effectiveness as an antibiotic.


    Institute of Scientific and Technical Information of China (English)

    ZHANG Ding-guo; ZHOU Sheng-feng


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

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

  18. Role of pocket flexibility in the modulation of estrogen receptor alpha by key residue arginine 394. (United States)

    Mu, Yunsong; Peng, Sufen; Zhang, Aiqian; Wang, Liansheng


    Estradiol derivatives, with similar structures as estradiol (E2) or estradiol metabolites, have been recognized to have detrimental health effects on wildlife and humans. However, data at the molecular level about interactions of these compounds with biological targets are still lacking. Herein, a flexible docking approach was used to characterize the molecular interaction of nine estradiol derivatives with estrogen receptor alpha (ERα) in the ligand-binding domain. All ligands were docked in the buried hydrophobic cavity of the steroid hormone pocket. In addition, the plasticity of an active site was also identified by reversing amino acid arginine 394 for better ligand-receptor binding affinity. Finally, bioassays based on genetically modified yeast strains were used to validate the quality of molecular simulation because of their rapidity and high sensitivity. The experimental findings about logarithm values of the median effective concentration (EC50) value had a linear correlation with computational binding affinity from molecular docking, which described a pattern of interaction between estradiol derivatives and ER. The estrogenic activity of all compounds, although more or less lower than E2, was proved to possess high severe environmental risks. Considering the sidechain flexibility in the ligand binding pocket, 17α-ethylestradiol-3-cyclopentylether was reported to correlate highly significantly with known induced fit conformational changes based upon proof-of-principle calculations on human ERα with the preservation of a strong salt bridge between glutamic acid 353 and arginine 394.

  19. Competitive Binding of Natural Amphiphiles with Graphene Derivatives (United States)

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


    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.

  20. Ligand Binding Thermodynamics in Drug Discovery: Still a Hot Tip? (United States)

    Geschwindner, Stefan; Ulander, Johan; Johansson, Patrik


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

  1. Terms of Binding

    NARCIS (Netherlands)

    Sevcenco, A.


    The present dissertation aimed at achieving two goals. First, it constitutes an attempt to widen the search for phenomena that bear relevance to the idea that binding has a syntactic residue and is not, therefore, an exclusively semantic matter. Second, it tried to provide the technical means to acc

  2. Binding and Bulgarian

    NARCIS (Netherlands)

    Schürcks-Grozeva, Lilia Lubomirova


    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

  3. MD-2 binds cholesterol. (United States)

    Choi, Soo-Ho; Kim, Jungsu; Gonen, Ayelet; Viriyakosol, Suganya; Miller, Yury I


    Cholesterol is a structural component of cellular membranes, which is transported from liver to peripheral cells in the form of cholesterol esters (CE), residing in the hydrophobic core of low-density lipoprotein. Oxidized CE (OxCE) is often found in plasma and in atherosclerotic lesions of subjects with cardiovascular disease. Our earlier studies have demonstrated that OxCE activates inflammatory responses in macrophages via toll-like receptor-4 (TLR4). Here we demonstrate that cholesterol binds to myeloid differentiation-2 (MD-2), a TLR4 ancillary molecule, which is a binding receptor for bacterial lipopolysaccharide (LPS) and is indispensable for LPS-induced TLR4 dimerization and signaling. Cholesterol binding to MD-2 was competed by LPS and by OxCE-modified BSA. Furthermore, soluble MD-2 in human plasma and MD-2 in mouse atherosclerotic lesions carried cholesterol, the finding supporting the biological significance of MD-2 cholesterol binding. These results help understand the molecular basis of TLR4 activation by OxCE and mechanisms of chronic inflammation in atherosclerosis.

  4. Sequential memory: Binding dynamics (United States)

    Afraimovich, Valentin; Gong, Xue; Rabinovich, Mikhail


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

  5. Cellulose binding domain proteins (United States)

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


    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.

  6. Probabilistic inference of transcription factor binding from multiple data sources.

    Directory of Open Access Journals (Sweden)

    Harri Lähdesmäki

    Full Text Available An important problem in molecular biology is to build a complete understanding of transcriptional regulatory processes in the cell. We have developed a flexible, probabilistic framework to predict TF binding from multiple data sources that differs from the standard hypothesis testing (scanning methods in several ways. Our probabilistic modeling framework estimates the probability of binding and, thus, naturally reflects our degree of belief in binding. Probabilistic modeling also allows for easy and systematic integration of our binding predictions into other probabilistic modeling methods, such as expression-based gene network inference. The method answers the question of whether the whole analyzed promoter has a binding site, but can also be extended to estimate the binding probability at each nucleotide position. Further, we introduce an extension to model combinatorial regulation by several TFs. Most importantly, the proposed methods can make principled probabilistic inference from multiple evidence sources, such as, multiple statistical models (motifs of the TFs, evolutionary conservation, regulatory potential, CpG islands, nucleosome positioning, DNase hypersensitive sites, ChIP-chip binding segments and other (prior sequence-based biological knowledge. We developed both a likelihood and a Bayesian method, where the latter is implemented with a Markov chain Monte Carlo algorithm. Results on a carefully constructed test set from the mouse genome demonstrate that principled data fusion can significantly improve the performance of TF binding prediction methods. We also applied the probabilistic modeling framework to all promoters in the mouse genome and the results indicate a sparse connectivity between transcriptional regulators and their target promoters. To facilitate analysis of other sequences and additional data, we have developed an on-line web tool, ProbTF, which implements our probabilistic TF binding prediction method using multiple

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

    DEFF Research Database (Denmark)

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


    Folate is an essential vitamin involved in a number of biological processes. High affinity folate binding proteins (FBPs) exist both as glycosylphosphatidylinositol-linked, membrane associated folate binding proteins and as soluble FBPs in plasma and some secretory fluids such as milk, saliva...... to bind and mediate cellular uptake of FBP. Surface plasmon resonance analysis shows binding of bovine and human milk FBP to immobilized megalin, but not to low density lipoprotein receptor related protein. Binding of (125)I-labeled folate binding protein (FBP) to sections of kidney proximal tubule, known...

  8. Exploring Protein-Peptide Binding Specificity through Computational Peptide Screening.

    Directory of Open Access Journals (Sweden)

    Arnab Bhattacherjee


    Full Text Available The binding of short disordered peptide stretches to globular protein domains is important for a wide range of cellular processes, including signal transduction, protein transport, and immune response. The often promiscuous nature of these interactions and the conformational flexibility of the peptide chain, sometimes even when bound, make the binding specificity of this type of protein interaction a challenge to understand. Here we develop and test a Monte Carlo-based procedure for calculating protein-peptide binding thermodynamics for many sequences in a single run. The method explores both peptide sequence and conformational space simultaneously by simulating a joint probability distribution which, in particular, makes searching through peptide sequence space computationally efficient. To test our method, we apply it to 3 different peptide-binding protein domains and test its ability to capture the experimentally determined specificity profiles. Insight into the molecular underpinnings of the observed specificities is obtained by analyzing the peptide conformational ensembles of a large number of binding-competent sequences. We also explore the possibility of using our method to discover new peptide-binding pockets on protein structures.

  9. Structure of the microtubule-binding domain of flagellar dynein. (United States)

    Kato, Yusuke S; Yagi, Toshiki; Harris, Sarah A; Ohki, Shin-ya; Yura, Kei; Shimizu, Youské; Honda, Shinya; Kamiya, Ritsu; Burgess, Stan A; Tanokura, Masaru


    Flagellar dyneins are essential microtubule motors in eukaryotes, as they drive the beating motions of cilia and flagella. Unlike myosin and kinesin motors, the track binding mechanism of dyneins and the regulation between the strong and weak binding states remain obscure. Here we report the solution structure of the microtubule-binding domain of flagellar dynein-c/DHC9 (dynein-c MTBD). The structure reveals a similar overall helix-rich fold to that of the MTBD of cytoplasmic dynein (cytoplasmic MTBD), but dynein-c MTBD has an additional flap, consisting of an antiparallel b sheet. The flap is positively charged and highly flexible. Despite the structural similarity to cytoplasmic MTBD, dynein-c MTBD shows only a small change in the microtubule- binding affinity depending on the registry change of coiled coil-sliding, whereby lacks the apparent strong binding state. The surface charge distribution of dynein-c MTBD also differs from that of cytoplasmic MTBD, which suggests a difference in the microtubule-binding mechanism.

  10. Global Analysis of a Flexible Riser

    Institute of Scientific and Technical Information of China (English)

    Liping Sun; Bo Qi


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

  11. Intermittent Swimming with a Flexible Propulsor (United States)

    Akoz, Emre; Zeyghami, Samane; Moored, Keith


    Some animals propel themselves by using an intermittent swimming gait known as a burst-and-glide or a burst-and-coast motion. These swimmers tend to have a more pronounced pitching of their caudal fins than heaving leading to low non-dimensional heave-to-pitch ratios. Recent work has shown that when this ratio is sufficiently low the efficiency of an intermittently heaving/pitching airfoil can be significantly improved over a continuously oscillating airfoil. However, fish that swim with an intermittent gait, such as cod and saithe, do not have rigid fins, but instead have highly flexible fins. To examine the performance and flow structures of an intermittent swimmer with a flexible propulsor, a fast boundary element method solver strongly coupled with a torsional-spring structural model was developed. A self-propelled virtual body combined with a flexible-hinged pitching airfoil is used to model a free-swimming animal and its flexible caudal fin. The duty cycle of the active to the coasting phase of motion, the torsional spring flexibility and the forcing frequency are all varied. The cost-of-transport and the swimming speed are measured and connected to the observed wake patterns. Supported by the Office of Naval Research under Program Director Dr. Bob Brizzolara, MURI Grant Number N00014-14-1-0533.

  12. Becoming More Systematic about Flexible Learning: Beyond Time and Distance (United States)

    de Boer, Wim; Collis, Betty


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

  13. Flexible Labour Strategy in the Dutch Automotive Industry

    NARCIS (Netherlands)

    Riemsdijk, van Maarten; Leede, de Jan


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

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

    NARCIS (Netherlands)

    Boer, de Wim; Collis, Betty


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

  15. Combinatorial Synthesis, Screening, and Binding Studies of Highly Functionalized Polyamino-amido Oligomers for Binding to Folded RNA

    Directory of Open Access Journals (Sweden)

    Jonathan K. Pokorski


    Full Text Available Folded RNA molecules have recently emerged as critical regulatory elements in biological pathways, serving not just as carriers of genetic information but also as key components in enzymatic assemblies. In particular, the transactivation response element (TAR of the HIV genome regulates transcriptional elongation by interacting specifically with the Tat protein, initiating the recruitment of the elongation complex. Preventing this interaction from occurring in vivo halts HIV replication, thus making RNA-binding molecules an intriguing pharmaceutical target. Using α-amino acids as starting materials, we have designed and synthesized a new class of polyamino-amido oligomers, called PAAs, specifically for binding to folded RNA structures. The PAA monomers were readily incorporated into a 125-member combinatorial library of PAA trimers. In order to rapidly assess RNA binding, a quantum dot-based fluorescent screen was developed to visualize RNA binding on-resin. The binding affinities of hits were quantified using a terbium footprinting assay, allowing us to identify a ligand (SFF with low micromolar affinity (kd=14 μM for TAR RNA. The work presented herein represents the development of a flexible scaffold that can be easily synthesized, screened, and subsequently modified to provide ligands specific for binding to folded RNAs.

  16. Experimental validation of flexible robot arm modeling and control (United States)

    Ulsoy, A. Galip


    Flexibility is important for high speed, high precision operation of lightweight manipulators. Accurate dynamic modeling of flexible robot arms is needed. Previous work has mostly been based on linear elasticity with prescribed rigid body motions (i.e., no effect of flexible motion on rigid body motion). Little or no experimental validation of dynamic models for flexible arms is available. Experimental results are also limited for flexible arm control. Researchers include the effects of prismatic as well as revolute joints. They investigate the effect of full coupling between the rigid and flexible motions, and of axial shortening, and consider the control of flexible arms using only additional sensors.

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

    Directory of Open Access Journals (Sweden)

    Michael P. Mazanetz


    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.

  18. Investigation of the flexibility of protein kinases implicated in the pathology of Alzheimer's disease. (United States)

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


    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.

  19. Subsea flexible flowline installation issues and solutions

    Institute of Scientific and Technical Information of China (English)

    Kevin Huang


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

  20. Design Space of Flexible Multigigabit LDPC Decoders

    Directory of Open Access Journals (Sweden)

    Philipp Schläfer


    Full Text Available Multigigabit LDPC decoders are demanded by standards like IEEE 802.15.3c and IEEE 802.11ad. To achieve the high throughput while supporting the needed flexibility, sophisticated architectures are mandatory. This paper comprehensively presents the design space for flexible multigigabit LDPC applications for the first time. The influence of various design parameters on the hardware is investigated in depth. Two new decoder architectures in a 65 nm CMOS technology are presented to further explore the design space. In the past, the memory domination was the bottleneck for throughputs of up to 1 Gbit/s. Our systematic investigation of column- versus row-based partially parallel decoders shows that this is no more a bottleneck for multigigabit architectures. The evolutionary progress in flexible multigigabit LDPC decoder design is highlighted in an extensive comparison of state-of-the-art decoders.

  1. Creating flexible work arrangements through idiosyncratic deals. (United States)

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


    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.

  2. 3-D Integrated Flexible Glass Photonics

    CERN Document Server

    Li, Lan; Qiao, Shutao; Zou, Yi; Danto, Sylvain; Richardson, Kathleen; Musgraves, J David; Lu, Nanshu; Hu, Juejun


    Photonic integration on plastic substrates enables emerging applications ranging from flexible interconnects to conformal sensors on biological tissues. Such devices are traditionally fabricated using pattern transfer, which is complicated and has limited integration capacity. Here we pioneered a monolithic approach to realize flexible, high-index-contrast glass photonics with significantly improved processing throughput and yield. Noting that the conventional multilayer bending theory fails when laminates have large elastic mismatch, we derived a mechanics theory accounting for multiple neutral axes in one laminated structure to accurately predict its strain-optical coupling behavior. Through combining monolithic fabrication and local neutral axis designs, we fabricated devices that boast record optical performance (Q=460,000) and excellent mechanical flexibility enabling repeated bending down to sub-millimeter radius without measurable performance degradation, both of which represent major improvements over...

  3. Implications of resistance exercise practice to flexibility

    Directory of Open Access Journals (Sweden)

    Cristiane Eri Shiromoto


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

  4. Progress on control experiments of flexible structures (United States)

    Juang, Jer-Nan


    Progress at the NASA Langley Research Center in the area of control experiments for flexible structures is described. First the author presents the experimental results for a linear model which represents slewing maneuvers of a generic space station solar panel carried out to evaluate experimentally some control technologies. Then the status of the rotational/translational maneuvering experiment of a flexible steel panel carried by a translation cart is presented. Finally, experimental results of the NASA minimast testbed using velocity command stepper motors as reaction mass reactors are shown. All the test configurations are briefly described, including actuator and sensor, test setup, and test software. The status of some research activities oriented primarily to the experimental methods for control of flexible structures is presented.

  5. Plasma jet printing for flexible substrates (United States)

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


    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.

  6. Controllability and observability for flexible spacecraft (United States)

    Hughes, P. C.; Skelton, R. E.


    Current interest in extended sensing and actuation for the control of flexible spacecraft has led to the use of modern multivariable control theory and the associated concepts of controllability and observability. This paper shows how to evaluate these properties on a mode-by-mode basis for flexible spacecraft control analysis. Relatively simple criteria are derived which indicate the degree of controllability (observability) of each mode in simple literal terms. These criteria provide physical insight and practical guidance on the type, number, and positioning of sensors and actuators. The results are interpreted for force and torque actuators, and for attitude and deformation measurements. To illustrate these ideas, sample controllability and observability 'surfaces' are presented for the Purdue generic flexible spacecraft model.

  7. Dynamic Scheduling of Flexible Job Shops

    Institute of Scientific and Technical Information of China (English)

    SHAHID Ikramullah Butt; SUN Hou-fang


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

  8. Flexible Electronics Development Supported by NASA (United States)

    Baumann, Eric


    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.

  9. Flexible Developing System for Modern Instrument Manufacturing

    Institute of Scientific and Technical Information of China (English)


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

  10. The influence of strength, flexibility, and simultaneous training on flexibility and strength gains. (United States)

    Simão, Roberto; Lemos, Adriana; Salles, Belmiro; Leite, Thalita; Oliveira, Élida; Rhea, Matthew; Reis, Victor Machado


    The purpose of this study was to examine the strength and flexibility gains after isolated or simultaneous strength and flexibility training after 16 weeks. Eighty sedentary women were randomly assigned to 1 of 4 groups: strength training (ST; n = 20), flexibility training (FLEX) (n = 20), combination of both (ST + FLEX; n = 20) and control group (CG; n = 20). All the groups performed pre and posttraining sit and reach test to verify the flexibility level and 10RM test for leg press and bench press exercises. The training protocol for all groups, except for the CG, included 3 weekly sessions, in alternated days, totaling 48 sessions. Strength training was composed of 8 exercises for upper and lower body, executed in 3 sets of periodized training. The flexibility training was composed of static stretching exercises that involved upper and lower body. Results showed that ST (30 ± 2.0 to 36 ± 3.0 cm), ST + FLEX (31 ± 1.0 to 42 ± 4.0 cm), and FLEX (32 ± 3.0 to 43 ± 2.0 cm) significantly increased in flexibility in relation to baseline and to CG (30 ± 2.0 to 30 ± 2.0 cm); however, no significant differences were observed between the treatment conditions. Strength tests demonstrated that ST and ST + FLEX significantly increased 10RM when compared to baseline, FLEX, and the CG. In conclusion, short-term strength training increases flexibility and strength in sedentary adult women. Strength training may contribute to the development and maintenance of flexibility even without the inclusion of additional stretching, but strength and flexibility can be prescribed together to get optimal improvements in flexibility.

  11. Human resource flexibility and job satisfaction: empirical study



    Treball final de Grau en Administració d’Empreses. Codi: AE1049. Curs acadèmic 2014-2015 Flexibility is every day more important for organizations due to the environmental changes. One way for organization to get that flexibility is through human resources flexibility, so this is becoming essential for organizations. The main aim of this study is to examine the effects of flexible human resources practices, specifically quantitative flexibility, on job satisfaction. We will do ...

  12. Influence of temperature on characteristics properties of flexible coupling



    The presented article deals with issue of characteristics changes of flexible shaft couplings used in drive systems of transport devices (dynamic torsional stiffness and damping coefficient) which is caused by influence of increase or decrease of flexible elements temperature. The influence is presented on a unit and percentage change of dynamic characteristics of four selected flexible couplings with rubber, plastic and pneumatic flexible elements. Identification of influence of flexible ele...

  13. Control of nonlinear flexible space structures (United States)

    Shi, Jianjun

    With the advances made in computer technology and efficiency of numerical algorithms over last decade, the MPC strategies have become quite popular among control community. However, application of MPC or GPC to flexible space structure control has not been explored adequately in the literature. The work presented in this thesis primarily focuses on application of GPC to control of nonlinear flexible space structures. This thesis is particularly devoted to the development of various approximate dynamic models, design and assessment of candidate controllers, and extensive numerical simulations for a realistic multibody flexible spacecraft, namely, Jupiter Icy Moons Orbiter (JIMO)---a Prometheus class of spacecraft proposed by NASA for deep space exploratory missions. A stable GPC algorithm is developed for Multi-Input-Multi-Output (MIMO) systems. An end-point weighting (penalty) is used in the GPC cost function to guarantee the nominal stability of the closed-loop system. A method is given to compute the desired end-point state from the desired output trajectory. The methodologies based on Fake Algebraic Riccati Equation (FARE) and constrained nonlinear optimization, are developed for synthesis of state weighting matrix. This makes this formulation more practical. A stable reconfigurable GPC architecture is presented and its effectiveness is demonstrated on both aircraft as well as spacecraft model. A representative in-orbit maneuver is used for assessing the performance of various control strategies using various design models. Different approximate dynamic models used for analysis include linear single body flexible structure, nonlinear single body flexible structure, and nonlinear multibody flexible structure. The control laws evaluated include traditional GPC, feedback linearization-based GPC (FLGPC), reconfigurable GPC, and nonlinear dissipative control. These various control schemes are evaluated for robust stability and robust performance in the presence of

  14. Movable MEMS Devices on Flexible Silicon

    KAUST Repository

    Ahmed, Sally


    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

  15. Flexibility and rigidity, requirements for the function of proteins and protein pigment complexes. Eleventh Keilin memorial lecture. (United States)

    Huber, R


    Proteins may be rigid or flexible to various degrees as required for optimum function. Flexibility at the level of amino acid side-chains occurs universally and is important for binding and catalysis. Flexibility of large parts of a protein which rearrange or move are particularly interesting and will be discussed here. We differentiate between certain categories of large-scale flexibility although the boundaries between them are diffuse: flexibility of peptide segments, domain motions and order-disorder transitions of spatially contigous regions. The domains may be flexibly linked to allow rather unrestricted motion or the motion may be constrained to certain modes. The polypeptide segments linking the domains show characteristic structural features. The various categories of flexibility will be illustrated with the following examples. (a) Small protein proteinase inhibitors which are rather rigid molecules which provide binding surfaces complementary to their cognate proteases, but also show limited segmental flexibility and adaptation. (b) Large plasma inhibitors which exhibit large conformational changes upon interaction with proteases probably for regulatory purposes. (c) Pancreatic serine proteases which employ a disorder-order transition of their activation domain as a means to regulate enzymic activity. (d) Immunoglobulins in which rather unrestricted and also hinged domain motions occur in different parts of the molecule probably to allow binding to antigens in different arrangements. (e) Citrate synthase which adopts open and closed forms by a hinged domain motion to bind substrates and release products and to perform the catalytic condensation reaction, respectively. (f) The bifunctional multienzyme complex riboflavin synthase in which two enzymes (alpha and beta) catalyse two consecutive enzymic reactions. The beta-subunits form a shell, in which the alpha-subunits are enclosed. Diffusional motion of the catalytic intermediates is therefore restricted

  16. Innovation in wearable and flexible antennas

    CERN Document Server

    Khaleel, Haider


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

  17. System Reduction and Damping of Flexible Structures

    DEFF Research Database (Denmark)

    Høgsberg, Jan Riess; Krenk, Steen


    An increasing number of flexible structures such as cable-stayed bridges, pedestrian bridges and high-rise buildings are fitted with local dampers to mitigate vibration problems. In principle the effect of local dampers can be analyzed by use of complex modes, e.g. in conjunction with an averaging...... frequency - containing the resulting modal damping via the imaginary part - is given by an explicit formula. For very flexible structures, e.g. cables, only moderate damping is involved, and the explicit approximation is very accurate. However, even for stiffer structures the explicit form gives a quite...

  18. Flexible robotics applications to multiscale manipulations

    CERN Document Server

    Grossard , Mathieu; Regnier, Stephane


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

  19. Flexible Polyhedral Surfaces with Two Flat Poses

    Directory of Open Access Journals (Sweden)

    Hellmuth Stachel


    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.

  20. Flexible alternatives to constant frequency systems (United States)

    Stewart-Wilson, John

    The use of hybrid systems in which variable frequency is used as generated, with a proportion being converted to constant frequency by electronic conversion, is examined as a flexible alternative to constant frequency systems. Here, some practical solutions to the technical issues raised by adopting the more flexible approach to electrical system generation are presented. In particular, attention is given to the frequency ranges used, impact on aircraft equipment, motor-driven equipment, transformer rectifier units, lighting, and avionics. The discussion also covers fan-assisted galley ovens, system architecture, special airworthiness requirements, and power quality.

  1. Fabrication of SWCNT based flexible chemiresistor (United States)

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


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

  2. Flexible input, dazzling output with IBM i

    CERN Document Server

    Victória-Pereira, Rafael


    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

  3. Adaptive Fuzzy Attitude Control of Flexible Satellite

    Institute of Scientific and Technical Information of China (English)

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


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

  4. Flexible method for Boolean information retrieval

    Energy Technology Data Exchange (ETDEWEB)

    Salton, G.; Wu, H.


    A new flexible retrieval system is described which makes it possible to relax the strict conditions of Boolean query logic thereby retrieving useful items that are rejected in a conventional retrieval situation. The query structure inherent in the Boolean system is preserved, while at the same time weighted terms may be incorporated into both queries and stored documents; the retrieved output can also be ranked in strict similarity order with the user queries. A conventional retrieval system can be modified to make use of the flexible metric system. Laboratory tests indicate that the extended system produces better retrieval output than either the Boolean or the vector processing systems. 11 references.

  5. ANFIS Modelling of Flexible Plate Structure

    Directory of Open Access Journals (Sweden)

    A. A. M. Al-Khafaji


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

  6. Effects of defeat stress on behavioral flexibility in males and females: modulation by the mu-opioid receptor. (United States)

    Laredo, Sarah A; Steinman, Michael Q; Robles, Cindee F; Ferrer, Emilio; Ragen, Benjamin J; Trainor, Brian C


    Behavioral flexibility is a component of executive functioning that allows individuals to adapt to changing environmental conditions. Independent lines of research indicate that the mu opioid receptor (MOR) is an important mediator of behavioral flexibility and responses to psychosocial stress. The current study bridges these two lines of research and tests the extent to which social defeat and MOR affect behavioral flexibility and whether sex moderates these effects in California mice (Peromyscus californicus). Males and females assigned to social defeat or control conditions were tested in a Barnes maze. In males, defeat impaired behavioral flexibility but not acquisition. Female performance was unaffected by defeat. MOR binding in defeated and control mice in the orbitofrontal cortex (OFC), striatum and hippocampus was examined via autoradiography. Stressed males had reduced MOR binding in the OFC whereas females were unaffected. The MOR antagonist beta-funaltrexamine (1 mg/kg) impaired performance in males naïve to defeat during the reversal phase but had no effect on females. Finally, we examined the effects of the MOR agonist morphine (2.5 and 5 mg/kg) on stressed mice. As expected, morphine improved behavioral flexibility in stressed males. The stress-induced deficits in behavioral flexibility in males are consistent with a proactive coping strategy, including previous observations that stressed male California mice exhibit strong social approach and aggression. Our pharmacological data suggest that a down-regulation of MOR signaling in males may contribute to sex differences in behavioral flexibility following stress. This is discussed in the framework of coping strategies for individuals with mood disorders.

  7. Binding Principles A and B

    Institute of Scientific and Technical Information of China (English)



    This paper focuses on the discussion of how Binding Principle A and Binding Principe B help with the interpretation of reference in English and Chinese. They are supposedly universal across languages.

  8. 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.

  9. A chemical chaperone induces inhomogeneous conformational changes in flexible proteins. (United States)

    Hamdane, Djemel; Velours, Christophe; Cornu, David; Nicaise, Magali; Lombard, Murielle; Fontecave, Marc


    Organic osmolytes also known as chemical chaperones are major cellular compounds that favor, by an unclear mechanism, protein's compaction and stabilization of the native state. Here, we have examined the chaperone effect of the naturally occurring trimethylamine N-oxide (TMAO) osmolyte on a loosely packed protein (LPP), known to be a highly flexible form, using an apoprotein mutant of the flavin-dependent RNA methyltransferase as a model. Thermal and chemical denaturation experiments showed that TMAO stabilizes the structural integrity of the apoprotein dramatically. The denaturation reaction is irreversible indicating that the stability of the apoprotein is under kinetic control. This result implies that the stabilization is due to a TMAO-induced reconfiguration of the flexible LPP state, which leads to conformational limitations of the apoprotein likely driven by favorable entropic contribution. Evidence for the conformational perturbation of the apoprotein had been obtained through several biophysical approaches notably analytical ultracentrifugation, circular dichroism, fluorescence spectroscopy, labelling experiments and proteolysis coupled to mass spectrometry. Unexpectedly, TMAO promotes an overall elongation or asymmetrical changes of the hydrodynamic shape of the apoprotein without alteration of the secondary structure. The modulation of the hydrodynamic properties of the protein is associated with diverse inhomogenous conformational changes: loss of the solvent accessible cavities resulting in a dried protein matrix; some side-chain residues initially buried become solvent exposed while some others become hidden. Consequently, the TMAO-induced protein state exhibits impaired capability in the flavin binding process. Our study suggests that the nature of protein conformational changes induced by the chemical chaperones may be specific to protein packing and plasticity. This could be an efficient mechanism by which the cell controls and finely tunes the

  10. Prediction of calcium-binding sites by combining loop-modeling with machine learning

    Directory of Open Access Journals (Sweden)

    Altman Russ B


    Full Text Available Abstract Background Protein ligand-binding sites in the apo state exhibit structural flexibility. This flexibility often frustrates methods for structure-based recognition of these sites because it leads to the absence of electron density for these critical regions, particularly when they are in surface loops. Methods for recognizing functional sites in these missing loops would be useful for recovering additional functional information. Results We report a hybrid approach for recognizing calcium-binding sites in disordered regions. Our approach combines loop modeling with a machine learning method (FEATURE for structure-based site recognition. For validation, we compared the performance of our method on known calcium-binding sites for which there are both holo and apo structures. When loops in the apo structures are rebuilt using modeling methods, FEATURE identifies 14 out of 20 crystallographically proven calcium-binding sites. It only recognizes 7 out of 20 calcium-binding sites in the initial apo crystal structures. We applied our method to unstructured loops in proteins from SCOP families known to bind calcium in order to discover potential cryptic calcium binding sites. We built 2745 missing loops and evaluated them for potential calcium binding. We made 102 predictions of calcium-binding sites. Ten predictions are consistent with independent experimental verifications. We found indirect experimental evidence for 14 other predictions. The remaining 78 predictions are novel predictions, some with intriguing potential biological significance. In particular, we see an enrichment of beta-sheet folds with predicted calcium binding sites in the connecting loops on the surface that may be important for calcium-mediated function switches. Conclusion Protein crystal structures are a potentially rich source of functional information. When loops are missing in these structures, we may be losing important information about binding sites and active

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

    DEFF Research Database (Denmark)

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


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

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

    Directory of Open Access Journals (Sweden)

    Anders Gerd


    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

  13. The impact of ligands on the structure and flexibility of sulfotransferases: a molecular dynamics simulation study. (United States)

    Zhao, Li; Zhang, Pupu; Long, Shiyang; Wang, Linlin; Tian, Pu


    Sulfotransferases catalyze transfer of the sulfuryl-group (-SO3) from 3'-phosphoadenosine 5'-phosphosulfate (PAPS) to a large number of substrates. They play an important role in phase II metabolic process. The impact of the cofactor (PAPS) on the structure and flexibility of the enzyme has been studied extensively, and the response of the active-cap region to cofactor binding was proposed as the molecular basis for substrate selectivity. In this study, individual and cooperative effects of the cofactor and substrate on the structure and flexibility of the enzyme were investigated. Molecular dynamics simulations were performed for four systems, including free enzyme, binary complexes (cofactor or substrate bound enzyme) and ternary complex (both cofactor and substrate bound enzyme). The influence of ligands (the cofactor and the substrate) on the structure and flexibility of the enzyme, especially that of the active-site cap region, was analyzed. Moreover, mutual structural impact of the ligands was examined as well. The results show that the impact of both the cofactor and the substrate was significant. Our study indicated that the substrate, such as lithocholic acid (LCA), participated in regulating the structure and flexibility of the enzyme actively rather than merely being selected passively. Additionally, the observed synergistic effects of the cofactor and the substrate demonstrated the importance of examining both ligands in understanding enzymes.

  14. Stiffness Formulation of Flexible Bucket Foundation

    DEFF Research Database (Denmark)

    Ibsen, Lars Bo; Liingaard, Morten; Larsen, Kim André

    The response of offshore wind turbines e.g. static, eigen frequencies and eigen modes, are affected by elastic properties of the foundation and the subsoil. The Elastic Macro Model is developed to evaluate the soil-structure interaction of flexible bucket foundations for offshore wind turbines so...

  15. II Conferencia internacional de pavimentos flexibles

    Directory of Open Access Journals (Sweden)

    Editorial, Equipo


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

  16. RMB Reform: Flexible, Yet True to Form

    Institute of Scientific and Technical Information of China (English)


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

  17. A flexible infrared sensor for tissue oximetry

    DEFF Research Database (Denmark)

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


    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...

  18. Can counter-stereotypes boost flexible thinking?

    NARCIS (Netherlands)

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


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

  19. Transputer control of a flexible robot link

    NARCIS (Netherlands)

    Stavenuiter, A.C.J.; Reehorst, ter G.; Bakkers, A.W.P.


    The applicability of transputers in control systems is investigated. This is done by implementing a controller for a flexible robot arm with one degree of freedom on a system consisting of an IBM-AT and four transputers. It is found that a control system with transputers offers a great improvement c


    DEFF Research Database (Denmark)


    A polymer-based flexible structure with integrated sensing/actuator means is presented. Conventionally, silicon has been used as a piezo-resistive material due to its high gauge factor and thereby high sensitivity to strain changes in a sensor. By using the fact that e.g. an SU-8 based polymer...

  1. Trajectory Control for Very Flexible Aircraft (United States)


    total airspeed and the classic aircraft longitudinal , lateral, and vertical velocity components are u positive out the nose, v positive out the right...wing flexibility is a secondary and minimal contribution to aircraft longitudinal motion. Using this assumption and the previous assumptions of

  2. Flexible Sensor Network Reprogramming for Logistics

    NARCIS (Netherlands)

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


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

  3. Internationalization:The Key to RMB Flexibility

    Institute of Scientific and Technical Information of China (English)


    Recently,the fast appreciation of the Chinese currency has become a major concern both at home and abroad.Ba Shusong,a researcher with the Development Research Center of the State Council,in a recent article for the 21st Century Business Herald,suggested that the renminbi exchange rate can become more flexible if it is fully internationalized.

  4. Valuing Flexibility in Career Training Decisions (United States)

    Yahanpath, Noel; Neal, Mark; McCormack, Shane


    Purpose: The purpose of this paper is to explore the nature and significance of flexibility in decisions about education and training options. This is done through an examination of the relevance of real options valuation (ROV) to our understanding of educational and training choices. Through this examination, the paper aims to contribute to the…

  5. Movement and stretching imagery during flexibility training. (United States)

    Vergeer, Ineke; Roberts, Jenny


    The aim of this study was to examine the effect of movement and stretching imagery on increases in flexibility. Thirty volunteers took part in a 4 week flexibility training programme. They were randomly assigned to one of three groups: (1) movement imagery, where participants imagined moving the limb they were stretching; (2) stretching imagery, where participants imagined the physiological processes involved in stretching the muscle; and (3) control, where participants did not engage in mental imagery. Active and passive range of motion around the hip was assessed before and after the programme. Participants provided specific ratings of vividness and comfort throughout the programme. Results showed significant increases in flexibility over time, but no differences between the three groups. A significant relationship was found, however, between improved flexibility and vividness ratings in the movement imagery group. Furthermore, both imagery groups scored significantly higher than the control group on levels of comfort, with the movement imagery group also scoring significantly higher than the stretching imagery group. We conclude that the imagery had stronger psychological than physiological effects, but that there is potential for enhancing physiological effects by maximizing imagery vividness, particularly for movement imagery.

  6. Flexible thin-film NFC tags

    NARCIS (Netherlands)

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


    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 char

  7. Flexible Hybrid Organic-Inorganic Perovskite Memory. (United States)

    Gu, Chungwan; Lee, Jang-Sik


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

  8. Flexible Thinking in Foreign Language Learning


    オフナー, マーク


    This paper illustrates the idea of flexible thinking which enables the foreign language student to better cope with communicating in the target language. This type of thinking allows the student to make better use of the foreign language regardless of fluency level, enhancing the learning process.

  9. Flexible Adaptivity in AEHS Using Policies

    NARCIS (Netherlands)

    Koesling, Arne; Krause, Daniel; Herder, Eelco


    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: Le

  10. 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)


    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.

  11. End-Point Control of Flexible Manipulators. (United States)


    to develop a universal robot end effector, capable of performing generic manipulation functions. This research focuses on the following advances toward...Tncrease the speed and precision of performing "slew arid touch" tasks by a flexible robot arri and second, to develop a universal robot end effector

  12. Balancing organization and flexibility in foraging dynamics. (United States)

    Tabone, Michaelangelo; Ermentrout, Bard; Doiron, Brent


    Proper pattern organization and reorganization are central problems facing many biological networks which thrive in fluctuating environments. However, in many cases the mechanisms that organize system activity oppose those that support behavioral flexibility. Thus, a balance between pattern organization and pattern flexibility is critically important for overall biological fitness. We study this balance in the foraging strategies of ant colonies exploiting food in dynamic environments. We present discrete time and space simulations of colony activity that uses a pheromone-based recruitment strategy biasing foraging towards a food source. After food relocation, the pheromone must evaporate sufficiently before foraging can shift colony attention to a new food source. The amount of food consumed within the dynamic environment depends non-monotonically on the pheromone evaporation time constant-with maximal consumption occurring at a time constant which balances trail formation and trail flexibility. A deterministic, 'mean field' model of pheromone and foragers on trails mimics our colony simulations. This reduced framework captures the essence of the flexibility-organization balance, and relates optimal pheromone evaporation to the timescale of the dynamic environment. We expect that the principles exposed in our study will generalize and motivate novel analysis across a broad range systems biology.

  13. Fast flexible electronics with strained silicon nanomembranes. (United States)

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


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

  14. Flexible neuroendoscopy with laser and microsystem technique (United States)

    Huewel, Norbert M.; Urban, Volker; Perneczky, A.


    The use of flexible neuroendoscopic techniques in neurosurgical procedures is routinely performed in the spinal canal and in the intracranial subdural space. Treated entities are syringomyelia, tumors with concomitant syrinxes in spinal cord, cystic legions in the subdural and subarachnoid space in the spinal canal as myelomeningoceles.

  15. Drag Coefficient of Thin Flexible Cylinder (United States)

    Subramanian, Chelakara; Gurram, Harika


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

  16. Simulation of Flexible Objects in Robotics

    DEFF Research Database (Denmark)

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


    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...

  17. Passivity Motivated Controller Design for Flexible Structures (United States)


    theoretical approach to the control of systems containing lumped joint flexibility is based on the exact linearization method. for a summary see [4...feedforward compensation (for the exact linearization ) and the feedback stabilization are intertwined and errors in the feedforward may affect the closed loop

  18. Flexible Interior-Impression-Molding Tray (United States)

    Anders, Jeffrey E.


    Device used inside combustion chamber of complicated shape for nondestructive evaluation of qualities of welds, including such features as offset, warping, misalignment of parts, and dropthrough. Includes flexible polypropylene tray trimmed to fit desired interior surface contour. Two neodymium boron magnets and inflatable bladder attached to tray. Tray and putty inserted in cavity to make mold of interior surface.

  19. On Quantification of Flexibility in Power Systems

    DEFF Research Database (Denmark)

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


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

  20. Flexible hydrogel-based functional composite materials (United States)

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


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

  1. Can counter-stereotypes boost flexible thinking?

    NARCIS (Netherlands)

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


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

  2. Flexible Twin Open Ring Metro WDM Network

    Institute of Scientific and Technical Information of China (English)

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


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

  3. Prevention of pulsations caused by flexible risers

    NARCIS (Netherlands)

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


    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

  4. A Model for Flexibly Editing CSCL Scripts (United States)

    Sobreira, Pericles; Tchounikine, Pierre


    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…

  5. Increases in rewards promote flexible behavior. (United States)

    Shen, Y Jeremy; Chun, Marvin M


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

  6. Flexible robot control: Modeling and experiments (United States)

    Oppenheim, Irving J.; Shimoyama, Isao


    Described here is a model and its use in experimental studies of flexible manipulators. The analytical model uses the equivalent of Rayleigh's method to approximate the displaced shape of a flexible link as the static elastic displacement which would occur under end rotations as applied at the joints. The generalized coordinates are thereby expressly compatible with joint motions and rotations in serial link manipulators, because the amplitude variables are simply the end rotations between the flexible link and the chord connecting the end points. The equations for the system dynamics are quite simple and can readily be formulated for the multi-link, three-dimensional case. When the flexible links possess mass and (polar moment of) inertia which are small compared to the concentrated mass and inertia at the joints, the analytical model is exact and displays the additional advantage of reduction in system dimension for the governing equations. Four series of pilot tests have been completed. Studies on a planar single-link system were conducted at Carnegie-Mellon University, and tests conducted at Toshiba Corporation on a planar two-link system were then incorporated into the study. A single link system under three-dimensional motion, displaying biaxial flexure, was then tested at Carnegie-Mellon.

  7. Switch Detection in Preschoolers' Cognitive Flexibility (United States)

    Chevalier, Nicolas; Wiebe, Sandra A.; Huber, Kristina L.; Espy, Kimberly Andrews


    The current study addressed the role of switch detection in cognitive flexibility by testing the effect of transition cues (i.e., cues that directly signal the need to switch or maintain a given task goal) in a cued set-shifting paradigm at 5 years of age. Children performed better, especially on switch trials, when transition cues were combined…

  8. Decision models in designing flexible production systems

    Directory of Open Access Journals (Sweden)

    Florescu Adriana


    Full Text Available Flexible production system is a complex whole that raise some issues in terms of its design and in relation to the conditions for implementing it. To implement a flexible production system configuration must be found that satisfies both economic and system performance requirements. The configuration which best meet the objectives of introducing a flexible production system must be sought in the set of alternatives defined and evaluated. In this paper we present a methodology of realising the configuration and complex evaluation of the analyzed system. It will be developed models which generate new alternative configurations, optimization and evaluation models of the performance of the flexible production system. This will create a framework for interactive decision support, user-oriented that can be used by management to solve this selection problem. The applicative character of the study consist in tracking of the technological process in real time using the developed software package on the designed system, based on mathematical models for configuration and optimization of the system.

  9. Dynamics of a Highly Flexible Protein

    DEFF Research Database (Denmark)

    Andersen, Lisbeth

    Protein dynamics are important for protein function. Especially, dynamics plays an important role in ligand-binding where the induced fit and conformational selection binding mechanisms represent the extremes in a continuum of dynamic mechanisms. The difference between the mechanisms lies......-resolution structures of NCBD in complex with four binding partners are currently known and while three of them are practically identical and resemble the major conformation in the unbound ensemble, one shows NCBD adopting an alternative and markedly different conformation. The mechanisms underlying this conformational...

  10. Synthesis and DNA-binding properties of novel DNA cyclo-intercalators containing purine-glucuronic acid hybrids. (United States)

    Zhang, Renshuai; Chen, Shaopeng; Wang, Xueting; Yu, Rilei; Li, Mingjing; Ren, Sumei; Jiang, Tao


    Novel DNA cyclo-intercalators, which incorporated two intercalator subunits linked by two bridges, were synthesized. Binding of the compounds to calf-thymus DNA was studied by fluorescence spectroscopy, and docking simulations were used to predict the binding modes of these cyclic compounds. The spectral data demonstrated that all of these compounds can interact with CT-DNA. The sugar moiety played an important role in the process of binding between the intercalators containing glucuronic acid and DNA. The length and flexibility of the connecting bridges affected the binding affinity of the resultant cyclo-intercalators. Docking simulations showed that compounds 7 and 8 interact with DNA as mono-intercalators.

  11. Dynamics of the substrate binding pocket in the presence of an inhibitor covalently attached to a fungal lipase. (United States)

    Peters, G H; Jensen, M O; Bywater, R P


    To gain insight into the mobility of the occupied ligand-binding pocket of the Rhizomucor miehei lipase we have conducted a rigorous molecular dynamics analysis. The covalently attached inhibitor, ethylhexylphosphonate, was employed as a mimic of the putative tetrahedral intermediate in the esterolytic reaction. Our results show that in this lipase, ligand recognition is influenced by the flexibility of the binding pocket, a feature that is common to many other enzymes. Several regions around the active site were found to move significantly to adapt to the inhibitor. These motions are correlated to the flexibility of the inhibitor. In particular, the hexyl chain of the inhibitor shows considerable mobility, and adjacent residues in the binding cleft accommodate to this flexibility. Pronounced fluctuations in the binding pocket induced by the flexibility of the inhibitor are observed in the hinge region F79-S82, the active site loop region W88-V95 and the protein regions P209-F215/H257-Y260. The flexibility in the regions F79-S82 and H257-Y260, where the shorter ethyl chain is located, indicates that additional space in this binding cleft region is available for accommodating a larger moiety. Fluctuations in the region W88-V95 and P209-F215 are due to the relatively short flexible hexyl carbon chain. This part of the binding pocket could be stiffened by the presence of a longer carbon chain. Though the inhibitor is covalently attached through the phosphonate moiety, interaction of the remainder of the molecule and the enzyme are determined by hydrophobic interactions, where the Van der Waals energies are approximately 25% lower than the electrostatic contributions.

  12. Production Flexibility in Extensive Beef Farming Systems

    Directory of Open Access Journals (Sweden)

    Laura Astigarraga


    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.

  13. Mapping of ligand-binding cavities in proteins. (United States)

    Andersson, C David; Chen, Brian Y; Linusson, Anna


    The complex interactions between proteins and small organic molecules (ligands) are intensively studied because they play key roles in biological processes and drug activities. Here, we present a novel approach to characterize and map the ligand-binding cavities of proteins without direct geometric comparison of structures, based on Principal Component Analysis of cavity properties (related mainly to size, polarity, and charge). This approach can provide valuable information on the similarities and dissimilarities, of binding cavities due to mutations, between-species differences and flexibility upon ligand-binding. The presented results show that information on ligand-binding cavity variations can complement information on protein similarity obtained from sequence comparisons. The predictive aspect of the method is exemplified by successful predictions of serine proteases that were not included in the model construction. The presented strategy to compare ligand-binding cavities of related and unrelated proteins has many potential applications within protein and medicinal chemistry, for example in the characterization and mapping of "orphan structures", selection of protein structures for docking studies in structure-based design, and identification of proteins for selectivity screens in drug design programs.

  14. Molecular Mechanisms of Pharmaceutical Drug Binding into Calsequestrin

    Directory of Open Access Journals (Sweden)

    ChulHee Kang


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

  15. 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: [University of Manchester, Brunswick Street, Manchester M13 9PL (United Kingdom)


    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.

  16. 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

  17. Conformational flexibility and structural dynamics in GPCR-mediated G protein activation: a perspective (United States)

    Preininger, Anita M.; Meiler, Jens; Hamm, Heidi


    Structure and dynamics of G proteins and their cognate receptors, both alone and in complex, are becoming increasingly accessible to experimental techniques. Understanding the conformational changes and timelines which govern these changes can lead to new insights into the processes of ligand binding and associated G protein activation. Experimental systems may involve the use of, or otherwise stabilize, non-native environments. This can complicate our understanding of structural and dynamical features of processes such as the ionic lock, Tryptophan toggle, and G protein flexibility. While elements in the receptor’s transmembrane helices and the C-terminal α5 helix of Gα undergo well defined structural changes, regions subject to conformational flexibility may be important in fine-tuning the interactions between activated receptors and G proteins. The pairing of computational and experimental approaches will continue to provide powerful tools to probe the conformation and dynamics of receptor-mediated G protein activation. PMID:23602809

  18. Motion and flexibility in human cytochrome p450 aromatase.

    Directory of Open Access Journals (Sweden)

    Wenhua Jiang

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

  19. In Silico Docking, Molecular Dynamics and Binding Energy Insights into the Bolinaquinone-Clathrin Terminal Domain Binding Site

    Directory of Open Access Journals (Sweden)

    Mohammed K. Abdel-Hamid


    Full Text Available Clathrin-mediated endocytosis (CME is a process that regulates selective internalization of important cellular cargo using clathrin-coated vesicles. Perturbation of this process has been linked to many diseases including cancer and neurodegenerative conditions. Chemical proteomics identified the marine metabolite, 2-hydroxy-5-methoxy-3-(((1S,4aS,8aS-1,4a,5-trimethyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-2-ylmethylcyclohexa- 2,5-diene-1,4-dione (bolinaquinone as a clathrin inhibitor. While being an attractive medicinal chemistry target, the lack of data about bolinaquinone’s mode of binding to the clathrin enzyme represents a major limitation for its structural optimization. We have used a molecular modeling approach to rationalize the observed activity of bolinaquinone and to predict its mode of binding with the clathrin terminal domain (CTD. The applied protocol started by global rigid-protein docking followed by flexible docking, molecular dynamics and linear interaction energy calculations. The results revealed the potential of bolinaquinone to interact with various pockets within the CTD, including the clathrin-box binding site. The results also highlight the importance of electrostatic contacts over van der Waals interactions for proper binding between bolinaquinone and its possible binding sites. This study provides a novel model that has the potential to allow rapid elaboration of bolinaquinone analogues as a new class of clathrin inhibitors.

  20. Nucleotide binding switches the information flow in ras GTPases. (United States)

    Raimondi, Francesco; Portella, Guillem; Orozco, Modesto; Fanelli, Francesca


    The Ras superfamily comprises many guanine nucleotide-binding proteins (G proteins) that are essential to intracellular signal transduction. The guanine nucleotide-dependent intrinsic flexibility patterns of five G proteins were investigated in atomic detail through Molecular Dynamics simulations of the GDP- and GTP-bound states (S(GDP) and S(GTP), respectively). For all the considered systems, the intrinsic flexibility of S(GDP) was higher than that of S(GTP), suggesting that Guanine Exchange Factor (GEF) recognition and nucleotide switch require higher amplitude motions than effector recognition or GTP hydrolysis. Functional mode, dynamic domain, and interaction energy correlation analyses highlighted significant differences in the dynamics of small G proteins and Gα proteins, especially in the inactive state. Indeed, S(GDP) of Gα(t), is characterized by a more extensive energy coupling between nucleotide binding site and distal regions involved in GEF recognition compared to small G proteins, which attenuates in the active state. Moreover, mechanically distinct domains implicated in nucleotide switch could be detected in the presence of GDP but not in the presence of GTP. Finally, in small G proteins, functional modes are more detectable in the inactive state than in the active one and involve changes in solvent exposure of two highly conserved amino acids in switches I and II involved in GEF recognition. The average solvent exposure of these amino acids correlates in turn with the rate of GDP release, suggesting for them either direct or indirect roles in the process of nucleotide switch. Collectively, nucleotide binding changes the information flow through the conserved Ras-like domain, where GDP enhances the flexibility of mechanically distinct portions involved in nucleotide switch, and favors long distance allosteric communication (in Gα proteins), compared to GTP.

  1. Nucleotide binding switches the information flow in ras GTPases.

    Directory of Open Access Journals (Sweden)

    Francesco Raimondi


    Full Text Available The Ras superfamily comprises many guanine nucleotide-binding proteins (G proteins that are essential to intracellular signal transduction. The guanine nucleotide-dependent intrinsic flexibility patterns of five G proteins were investigated in atomic detail through Molecular Dynamics simulations of the GDP- and GTP-bound states (S(GDP and S(GTP, respectively. For all the considered systems, the intrinsic flexibility of S(GDP was higher than that of S(GTP, suggesting that Guanine Exchange Factor (GEF recognition and nucleotide switch require higher amplitude motions than effector recognition or GTP hydrolysis. Functional mode, dynamic domain, and interaction energy correlation analyses highlighted significant differences in the dynamics of small G proteins and Gα proteins, especially in the inactive state. Indeed, S(GDP of Gα(t, is characterized by a more extensive energy coupling between nucleotide binding site and distal regions involved in GEF recognition compared to small G proteins, which attenuates in the active state. Moreover, mechanically distinct domains implicated in nucleotide switch could be detected in the presence of GDP but not in the presence of GTP. Finally, in small G proteins, functional modes are more detectable in the inactive state than in the active one and involve changes in solvent exposure of two highly conserved amino acids in switches I and II involved in GEF recognition. The average solvent exposure of these amino acids correlates in turn with the rate of GDP release, suggesting for them either direct or indirect roles in the process of nucleotide switch. Collectively, nucleotide binding changes the information flow through the conserved Ras-like domain, where GDP enhances the flexibility of mechanically distinct portions involved in nucleotide switch, and favors long distance allosteric communication (in Gα proteins, compared to GTP.

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

  3. Structures of mesophilic and extremophilic citrate synthases reveal rigidity and flexibility for function. (United States)

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


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

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

    Directory of Open Access Journals (Sweden)

    Wim De Boer


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

  5. Behavioral flexibility and problem solving in an invasive bird. (United States)

    Logan, Corina J


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

  6. Transmission of Infection by Flexible Gastrointestinal Endoscopy and Bronchoscopy

    NARCIS (Netherlands)

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


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

  7. Social performance cues induce behavioral flexibility in humans

    NARCIS (Netherlands)

    Toelch, U.; Bruce, M.J.; Meeus, M.T.H.; Reader, S.M.


    Behavioral flexibility allows individuals to react to environmental changes, but changing established behavior carries costs, with unknown benefits. Individuals may thus modify their behavioral flexibility according to the prevailing circumstances. Social information provided by the performance leve

  8. Polyaniline modified flexible conducting paper for cancer detection (United States)

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


    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.

  9. Arabidopsis thaliana dehydroascorbate reductase 2: Conformational flexibility during catalysis (United States)

    Bodra, Nandita; Young, David; Astolfi Rosado, Leonardo; Pallo, Anna; Wahni, Khadija; De Proft, Frank; Huang, Jingjing; Van Breusegem, Frank; Messens, Joris


    Dehydroascorbate reductase (DHAR) catalyzes the glutathione (GSH)-dependent reduction of dehydroascorbate and plays a direct role in regenerating ascorbic acid, an essential plant antioxidant vital for defense against oxidative stress. DHAR enzymes bear close structural homology to the glutathione transferase (GST) superfamily of enzymes and contain the same active site motif, but most GSTs do not exhibit DHAR activity. The presence of a cysteine at the active site is essential for the catalytic functioning of DHAR, as mutation of this cysteine abolishes the activity. Here we present the crystal structure of DHAR2 from Arabidopsis thaliana with GSH bound to the catalytic cysteine. This structure reveals localized conformational differences around the active site which distinguishes the GSH-bound DHAR2 structure from that of DHAR1. We also unraveled the enzymatic step in which DHAR releases oxidized glutathione (GSSG). To consolidate our structural and kinetic findings, we investigated potential conformational flexibility in DHAR2 by normal mode analysis and found that subdomain mobility could be linked to GSH binding or GSSG release. PMID:28195196

  10. Taming molecular flexibility to tackle rare diseases. (United States)

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


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

  11. Energy Flexibility of The Commercial Greenhouse Growers

    DEFF Research Database (Denmark)

    Ma, Zheng; Jørgensen, Bo Nørregaard


    The commercial greenhouses can provide energy flexibility with the artificial lighting usage. Therefore, the commercial greenhouse growers can potentially play an important role in the electricity market as providers of flexibility services with the technology and software readiness. This paper...... Parties) imbalance error. Two calculations are formulated to evaluate the monetary benefits for the commercial greenhouse growers’ participation in both business models. The positive results indicate potential and benefits for the Danish commercial greenhouse growers’ participation in the electricity...... takes Danish commercial growers and the Nordic regulating market as an example, to investigate the market potential with two business models. One business model is that commercial greenhouse growers directly participate in the regulating market. Another model is rescuing the BRPs’ (Balance Responsible...

  12. Screen-printed flexible MRI receive coils. (United States)

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


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

  13. Drop impact on a flexible fiber

    CERN Document Server

    Dressaire, Emilie; Boulogne, François; Stone, Howard A


    When droplets impact fibrous media, the liquid can be captured by the fibers or contact then break away. Previous studies have shown that the efficiency of drop capture by a rigid fiber depends on the impact velocity and defined a threshold velocity below which the drop is captured. However, it is necessary to consider the coupling of elastic and capillary effects to achieve a greater understanding of the capture process for soft substrates. Here, we study experimentally the dynamics of a single drop impacting on a thin flexible fiber. Our results demonstrate that the threshold capture velocity depends on the flexibility of fibers in a non-monotonic way. We conclude that tuning the mechanical properties of fibers can optimize the efficiency of droplet capture.

  14. Flexible Software Process Lines in Practice

    DEFF Research Database (Denmark)

    Kuhrmann, Marco; Ternité, Thomas; Friedrich, Jan


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

  15. Procedural Optimization Models for Multiobjective Flexible JSSP

    Directory of Open Access Journals (Sweden)

    Elena Simona NICOARA


    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.

  16. Computational Control of Flexible Aerospace Systems (United States)

    Sharpe, Lonnie, Jr.; Shen, Ji Yao


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

  17. Analysis of flexible structures under lateral impact

    Energy Technology Data Exchange (ETDEWEB)

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


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

  18. Flexible Bit Preservation on a National Basis

    DEFF Research Database (Denmark)

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


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

  19. Screen printed UHF antennas on flexible substrates (United States)

    Janeczek, Kamil; Młożniak, Anna; Kozioł, Grażyna; Araźna, Aneta; Jakubowska, Małgorzata; Bajurko, Paweł


    Printed electronics belongs to the most important developing electronics technologies. It provides new possibilities to produce low cost and large area devices. In its range several applications can be distinguished like printed batteries, OLED, biosensors, photovoltaic cells or RFID tags. In the presented investigation, antennas working in UHF frequency range were elaborated. It can be applied in the future for flexible RFID tags. To produce these antennas polymer paste with silver flakes was used. It was deposited on two flexible substrates (foil and photo paper) with screen printing techniques. After printing process surface profile, electrical and microwave parameters of performed antennas were measured using digital multimeter and network analyzer, relatively. Furthermore, a thickness of printed layers was measured.

  20. Balancing Flexibility and Security in Europe

    DEFF Research Database (Denmark)

    Russell, Helen; Leschke, Janine; Smith, Mark

    ) and 5 (2010) of the European Social Survey (ESS). The study asks how flexibility, security and welfare state configurations interact to influence overall levels of objective security (for example fixed-term contracts, unemployment), subjective job and employment security (employability) among various......This paper examines the relationship between so-called “flexicurity” systems and outcomes on insecurity and well-being for young people (15-34 years) in Europe during the great recession. A key tenet of this approach is that greater flexibility of labour supply is underpinned by a welfare system......, there is a risk that young people tend to experience greater job insecurity – objectively and subjectively – without the benefit of income security or employment security. We focus on objective and subjective insecurity and well-being drawing on data from the work, family and well-being modules in rounds 2 (2004...

  1. Is adapting to others codependency or flexibility? (United States)

    Davidhizar, R; Shearer, R A


    1. Many people use the word codependency without understanding its meaning. Codependency should be used to describe behaviors that have developed in a dysfunctional family in which priorities have become unbalanced, and energy is focused on ensuring that everything seems normal from the outside rather than focusing on the needs of individual family members. 2. Codependency may continue into a professional role and result in a manager who has low feelings of self-worth and a strong need for approval from others. 3. Flexibility is different from codependency. A flexible individual has strong and positive feelings of self-worth and is able to listen to opposing points of view and actively listen to others. Change and compromise are possible for this person.

  2. Flexible parylene-film optical waveguide arrays (United States)

    Yamagiwa, S.; Ishida, M.; Kawano, T.


    Modulation of neuronal activities by light [e.g., laser or light-emitting diode] using optogenetics is a powerful tool for studies on neuronal functions in a brain. Herein, flexible thin-film optical waveguide arrays based on a highly biocompatible material of parylene are reported. Parylene-C and -N thin layers with the different refractive indices form the clad and the core of the waveguide, respectively, and neural recording microelectrodes are integrated to record optical stimuli and electrical recordings simultaneously using the same alignment. Both theoretical and experimental investigations confirm that light intensities of more than 90% can propagate in a bent waveguide with a curvature radius of >5 mm. The proposed flexible thin-film waveguide arrays with microelectrodes can be used for numerous spherical bio-tissues, including brain and spinal cord samples.

  3. Energy Flexibility of The Commercial Greenhouse Growers

    DEFF Research Database (Denmark)

    Ma, Zheng; Jørgensen, Bo Nørregaard


    The commercial greenhouses can provide energy flexibility with the artificial lighting usage. Therefore, the commercial greenhouse growers can potentially play an important role in the electricity market as providers of flexibility services with the technology and software readiness. This paper...... takes Danish commercial growers and the Nordic regulating market as an example, to investigate the market potential with two business models. One business model is that commercial greenhouse growers directly participate in the regulating market. Another model is rescuing the BRPs’ (Balance Responsible...... Parties) imbalance error. Two calculations are formulated to evaluate the monetary benefits for the commercial greenhouse growers’ participation in both business models. The positive results indicate potential and benefits for the Danish commercial greenhouse growers’ participation in the electricity...

  4. Supporting Flexible Data Distribution in Software DSMs

    Institute of Scientific and Technical Information of China (English)

    洪锦伟; 陈国良; 张兆庆


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

  5. Flexible energy harvesting from hard piezoelectric beams (United States)

    Delnavaz, Aidin; Voix, Jérémie


    This paper presents design, multiphysics finite element modeling and experimental validation of a new miniaturized PZT generator that integrates a bulk piezoelectric ceramic onto a flexible platform for energy harvesting from the human body pressing force. In spite of its flexibility, the mechanical structure of the proposed device is simple to fabricate and efficient for the energy conversion. The finite element model involves both mechanical and piezoelectric parts of the device coupled with the electrical circuit model. The energy harvester prototype was fabricated and tested under the low frequency periodic pressing force during 10 seconds. The experimental results show that several nano joules of electrical energy is stored in a capacitor that is quite significant given the size of the device. The finite element model is validated by observing a good agreement between experimental and simulation results. the validated model could be used for optimizing the device for energy harvesting from earcanal deformations.

  6. Light trapping for flexible organic photovoltaics (United States)

    Park, Yoonseok; Berger, Jana; Will, Paul-Anton; Soldera, Marcos; Glatz, Bernhard; Müller-Meskamp, Lars; Taretto, Kurt; Fery, Andreas; Lasagni, Andrés. Fabián.; Vandewal, Koen; Leo, Karl


    Here we investigate light trapping substrates and electrodes for enhancing the performance of organic photovoltaics (OPVs). Their power conversion efficiency (PCE) can be improved by a factor of 1.16 using laser patterned PET substrates and by a factor of 1.13 using commercial, structured display films. Furthermore, we prepare light trapping electrodes using as flexible conductive polymer with embedded TiO2 nanoparticles, improving the PCE by a factor of 1.08 as compared to a neat polymer electrode. However, nano-imprinted conductive polymer electrodes does not provide light trapping effect due to the small size (50 nm) of the structures. Moreover flexible OPV devices, integrating the above light trapping elements, show non-degraded performance after bending tests.

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

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


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

  8. Simulating charge transport in flexible systems

    Directory of Open Access Journals (Sweden)

    Timothy Clark


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

  9. Flexible feature interface for multimedia sources (United States)

    Coffland, Douglas R.


    A flexible feature interface for multimedia sources system that includes a single interface for the addition of features and functions to multimedia sources and for accessing those features and functions from remote hosts. The interface utilizes the export statement: export "C" D11Export void FunctionName(int argc, char ** argv,char * result, SecureSession *ctrl) or the binary equivalent of the export statement.

  10. Flexible optical chemical sensor platform for BTX


    Arias Espinoza, Juan Diego; Sazhnikov, Viacheslav; Sabik, Sami; Ionov, Dmitriy; Smits, Edsger; Kalathimekkad, Sandeep; Van Steenberge, Geert; Alfimov, Michail; Posniak, Malgorzata; Schoo, Herman


    An in-plane flexible sensor platform for BTX detection was developed using low-cost patterning techniques and foil-based optical components. The platform was produced by a combination of laser patterning, inkjet printing and capillary filling. Key optical components such as lightguides, opticalcladding layers and metallic interconnections were realized on low cost substrates such as paper and PET. The sensing mechanism is based on the change in fluorescence spectra of a reporter dye, supporte...


    Directory of Open Access Journals (Sweden)

    Oleksandr Luppo


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

  12. Deployable radiator with flexible line loop (United States)

    Keeler, Bryan V. (Inventor); Lehtinen, Arthur Mathias (Inventor); McGee, Billy W. (Inventor)


    Radiator assembly (10) for use on a spacecraft (12) is provided including at least one radiator panel assembly (26) repeatably movable between a panel stowed position (28) and a panel deployed position (36), at least two flexible lines (40) in fluid communication with the at least one radiator panel assembly (26) and repeatably movable between a stowage loop (42) and a flattened deployed loop (44).

  13. Nonlinear Dynamics and Control of Flexible Structures (United States)


    Freedom," Ph.D. Thesis, Department of Theoretical and Applied Mechanics, Cornell University, in preparation. 5I I URI Reorts Islam , Saiful and Mircea...Theoretical and Applied Mechanics I S. Islam Civil and Environmental Engineering I 2! I 3 URI Accomplishments 3 -Nonlinear Dynamics and Chaos in Flexible...Structures with Symmetry," 31 (1991) 265-285. Islam , S. and M. Grigoriu, "Nonlinear Random Vibration of Pin-Jointed Trusses with Imperfections," in

  14. Flexible heating head for induction heating (United States)

    Fox, Robert L. (Inventor); Johnson, Samuel D. (Inventor); Coultrip, Robert H. (Inventor); Phillips, W. Morris (Inventor)


    An induction heating head includes a length of wire having first and second opposite ends and being wound in a flat spiral shape to form an induction coil, a capacitor connected to the first and second ends of the wire, the induction coil and capacitor defining a tank circuit, and a flexible, elastomeric body molded to encase the induction coil. When a susceptor is placed in juxtaposition to the body, and the tank circuit is powered, the susceptor is inductively heated.


    Institute of Scientific and Technical Information of China (English)

    A.Y.T.Leung; WuGuorong; ZhongWeifang


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

  16. Multimode FPGA with Flexible Embedded FPUS


    G.Murugaboopathi; S.Hariharasitaraman; Sankar, G.


    The Performance of field-programmable gate arrays used for Floating-point applications are poor due to complexity of floating-point arithmetic. Implementing floating-point units on FPGAs consume a large amount of resources. This makes FPGAs less attractive for use in floating-point intensive applications. There is a need for embedded FPUs in FPGAs. We proposed a flexible multimode embedded FPU for FPGAs that can be configured to perform a wide range of operations. The floatingpoint adder and ...

  17. Increasing flexibility in rangeland management during drought


    Kachergis, E; Derner, JD; Cutts, BB; Roche, LM; Eviner, VT; Lubell, MN; Tate, KW


    Extreme droughts like the recent 2011-2013 drought impacting the central and western United States present a challenge to sustaining livestock ranching operations and the ecosystem goods and services they produce. Wyoming ranchers manage half of this drought-prone state and are at the forefront of this challenge. We examined Wyoming ranchers' drought management strategies and how ranch characteristics affect drought management flexibility, a key component of resilience, through a mail survey....

  18. Analytic QCD Binding Potentials

    CERN Document Server

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


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


    Institute of Scientific and Technical Information of China (English)

    仲昕; 周兵; 杨汝清


    The flexible body modeling theory was demonstrated. An example of modeling a kind of automobile's front suspension as a multi-flexible system was shown. Finally, it shows that the simulation results of multi-flexible dynamic model more approach the road test data than those of multi-rigid dynamic model do. Thus, it is fully testified that using multi-flexible body theory to model is necessary and effective.

  20. Impact of Personnel Flexibility on Job Shop Scheduling

    Directory of Open Access Journals (Sweden)

    Ren Lin


    Full Text Available Considering the lack of the research on the relationship between HR flexibility and scheduling effect, a resource-competency matrix-based method was proposed in order to reveal the quantitative relationship between them. Meanwhile, a job shop scheduling model with HR flexibility was established and the improved genetic algorithm was used to solve the model. A case analysis demonstrated significant impact of HR flexibility on the scheduling effect, which provided valuable guidance for building flexible manufacturing systems.

  1. Free-form Flexible Lithium-Ion Microbattery

    KAUST Repository

    Kutbee, Arwa T.


    Wearable electronics need miniaturized, safe and flexible power sources. Lithium ion battery is a strong candidate as high performance flexible battery. The development of flexible materials for battery electrodes suffers from the limited material choices. In this work, we present integration strategy to rationally design materials and processes to report flexible inorganic lithium-ion microbattery with no restrictions on the materials used. The battery shows an enhanced normalized capacity of 147 μAh/cm2 when bent.

  2. Flexible automation and the loss of pooling synergy



    This paper focuses on the effects of flexible automation on the performance of a job shop. Flexible automated machines may significantly improve the delivery performance and the flow time of jobs. The insertion of a flexible automated system in a job shop, however, also has a counter effect on the manufacturing performance. This is caused by the reduction of pooling synergy due to the dedication implied by flexible automated machines. This paper investigates by means of a simulation study to ...

  3. Control of a Lightweight Flexible Robotic Arm Using Sliding Modes


    Ibone Lizarraga; Arantza Sanz; Victor Etxebarria


    This paper presents a robust control scheme for flexible link robotic manipulators, which is based on considering the flexible mechanical structure as a system with slow (rigid) and fast (flexible) modes that can be controlled separately. The rigid dynamics is controlled by means of a robust sliding-mode approach with wellestablished stability properties while an LQR optimal design is adopted for the flexible dynamics. Experimental results show that this composite approach achieves good close...

  4. Flexible lithium-ion planer thin-film battery

    KAUST Repository

    Kutbee, Arwa T.


    Commercialization of wearable electronics requires miniaturized, flexible power sources. Lithium ion battery is a strong candidate as the next generation high performance flexible battery. The development of flexible materials for battery electrodes suffers from the limited material choices. In this work, we present a flexible inorganic lithium-ion battery with no restrictions on the materials used. The battery showed an enhanced normalized capacity of 146 ??Ah/cm2.

  5. Flexible heartbeat sensor for wearable device. (United States)

    Kwak, Yeon Hwa; Kim, Wonhyo; Park, Kwang Bum; Kim, Kunnyun; Seo, Sungkyu


    We demonstrate a flexible strain-gauge sensor and its use in a wearable application for heart rate detection. This polymer-based strain-gauge sensor was fabricated using a double-sided fabrication method with polymer and metal, i.e., polyimide and nickel-chrome. The fabrication process for this strain-gauge sensor is compatible with the conventional flexible printed circuit board (FPCB) processes facilitating its commercialization. The fabricated sensor showed a linear relation for an applied normal force of more than 930 kPa, with a minimum detectable force of 6.25Pa. This sensor can also linearly detect a bending radius from 5mm to 100mm. It is a thin, flexible, compact, and inexpensive (for mass production) heart rate detection sensor that is highly sensitive compared to the established optical photoplethysmography (PPG) sensors. It can detect not only the timing of heart pulsation, but also the amplitude or shape of the pulse signal. The proposed strain-gauge sensor can be applicable to various applications for smart devices requiring heartbeat detection.

  6. Flexible Structural-Health-Monitoring Sheets (United States)

    Qing, Xinlin; Kuo, Fuo


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

  7. Granular materials interacting with thin flexible rods (United States)

    Neto, Alfredo Gay; Campello, Eduardo M. B.


    In this work, we develop a computational model for the simulation of problems wherein granular materials interact with thin flexible rods. We treat granular materials as a collection of spherical particles following a discrete element method (DEM) approach, while flexible rods are described by a large deformation finite element (FEM) rod formulation. Grain-to-grain, grain-to-rod, and rod-to-rod contacts are fully permitted and resolved. A simple and efficient strategy is proposed for coupling the motion of the two types (discrete and continuum) of materials within an iterative time-stepping solution scheme. Implementation details are shown and discussed. Validity and applicability of the model are assessed by means of a few numerical examples. We believe that robust, efficiently coupled DEM-FEM schemes can be a useful tool to the simulation of problems wherein granular materials interact with thin flexible rods, such as (but not limited to) bombardment of grains on beam structures, flow of granular materials over surfaces covered by threads of hair in many biological processes, flow of grains through filters and strainers in various industrial segregation processes, and many others.

  8. Ultrathin flexible dual band terahertz absorber (United States)

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


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

  9. Eddy Current Flexible Probes for Complex Geometries (United States)

    Gilles-Pascaud, C.; Decitre, J. M.; Vacher, F.; Fermon, C.; Pannetier, M.; Cattiaux, G.


    The inspection of materials used in aerospace, nuclear or transport industry is a critical issue for the safety of components exposed to stress or/and corrosion. The industry claims for faster, more sensitive, and more flexible techniques. Technologies based on Eddy Current (EC) flexible array probe and magnetic sensor with high sensitivity such as giant magneto-resistance (GMR) could be a good solution to detect surface-breaking flaws in complex shaped surfaces. The CEA has recently developed, with support from the French Institute for Radiological Protection and Nuclear Safety (IRSN), a flexible array probe based on micro-coils etched on Kapton. The probe's performances have been assessed for the inspection of reactor residual heat removal pipes, and for aeronautical applications within the framework of the European project VERDICT. The experimental results confirm the very good detection of narrow cracks on plane and curve shaped surfaces. This paper also describes the recent progresses concerning the application of GMR sensors to EC testing, and the results obtained for the detection of small surface breaking flaws.

  10. Silk Fibroin for Flexible Electronic Devices. (United States)

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


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

  11. Viscous pumping inspired by flexible propulsion

    CERN Document Server

    Arco, Roger M; Lauga, Eric; Zenit, Roberto


    Fluid-suspended microorganisms have evolved different swimming and feeding strategies in order to cope with an environment dominated by viscous effects. For instance ciliated organisms rely on the collective motion of flexible appendices to move and feed. By performing a non-reciprocal motion, flexible filaments can produce a net propulsive force, or pump fluid, in the absence of inertia. Inspired by such fundamental concept, we propose a strategy to produce macroscopic pumping and mixing in creeping flow. We measure experimentally the net motion of a Newtonian viscous fluid induced by the reciprocal motion of a flapper. When the flapper is rigid no net motion is induced. In contrast, when the flapper is made of a flexible material, a net fluid pumping is measured. We quantify the effectiveness of this pumping strategy and show that optimal pumping is achieved when the length of the flapper is on the same order as the elasto-hydrodynamic penetration length. We finally discuss the possible applications of flex...

  12. Symptomatic flexible flatfoot in adults: subtalar arthroereisis (United States)

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


    Flexible flatfoot is a common deformity in pediatric and adult populations. In this study, we aimed to evaluate the functional and radiographic results of subtalar arthroereisis in adult patients with symptomatic flexible flatfoot. We included 26 feet in 16 patients who underwent subtalar arthroereisis for symptomatic flexible flatfoot. Radiographic examination included calcaneal inclination angle, lateral talocalcaneal angle, Meary’s angle, anteroposterior talonavicular angle, and Kite’s angle. The clinical assessment was based on the American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot scale and a visual analog scale (VAS). The mean follow-up was 15.1±4.7 months. The mean preoperative AOFAS score was 53±6.6, while the mean AOFAS score at the last follow-up visit was 75±11.2 (P0.05); 8°±5.3° and 3.3±3 for Meary’s angles (Pflatfoot. This procedure provided radiological and functional recovery in our series of patients. PMID:26527876

  13. On the flexibility of phonetic categories (United States)

    Francis, Alexander L.; Nusbaum, Howard C.


    Research on phonetic category acquisition suggests that over the course of development children shift the relative weight given to various acoustic cues to particular phonetic categories [S. Nittrouer, J. Phon. 20, 1-32 (1992)]. Adults also show flexibility in acquiring second language categories and learning to recognize synthetic speech. In both cases listeners must shift attention among some acoustic cues and change the weighting and mapping of others. Recent research demonstrated that category-level feedback can induce adult listeners to shift attention between conflicting cues to native stop-consonant categories. Subsequent research showed that adult listeners also reorganize the distribution of their attention to acoustic cues in learning to better understand synthetic speech. Moreover, research on learning foreign phonetic contrasts suggests that listeners can learn to direct attention to unfamiliar acoustic cues. These results suggest that phonetic categories are flexible in terms of the nature and quality of the acoustic cues that define them. We argue that this flexibility is a consequence of the basic nature of the general mechanism that mediates speech perception: In order to resolve the problem of context-conditioned variability, listeners must dynamically modify attention to the acoustic signal in a context-dependent manner.

  14. Unlocking Flexibility: Energy Systems Integration [Guest Editorial

    Energy Technology Data Exchange (ETDEWEB)

    O' Malley, Mark; Kroposki, Benjamin


    The articles in this special section focus on energy systems integration (ESI). Electric power systems around the world are experiencing great changes, including the retirement of coal and nuclear plants along with a rapid increase in the use of natural gas turbines and variable renewable technologies such as wind and solar. There is also much more use of information and communications technologies to enhance the visibility and controllability of the grid. Flexibility of operation, the ability of a power system to respond to change in demand and supply, is critical to enable higher levels of variable generation. One way to unlock this potential flexibility is to tap into other energy domains. This concept of interconnecting energy domains is called ESI. ESI is the process of coordinating the operation and planning of energy systems across multiple pathways and/or geographical scales to deliver reliable, cost-effective energy services with minimal impact on the environment. Integrating energy domains adds flexibility to the electrical power system. ESI includes interactions among energy vectors and with other large-scale infrastructures including water, transport, and data and communications networks, which are an enabling technology for ESI.

  15. Non-contact intracellular binding of chloroplasts in vivo (United States)

    Li, Yuchao; Xin, Hongbao; Liu, Xiaoshuai; Li, Baojun


    Non-contact intracellular binding and controllable manipulation of chloroplasts in vivo was demonstrated using an optical fiber probe. Launching a 980-nm laser beam into a fiber, which was placed about 3 μm above the surface of a living plant (Hydrilla verticillata) leaf, enabled stable binding of different numbers of chloroplasts, as well as their arrangement into one-dimensional chains and two-dimensional arrays inside the leaf without damaging the chloroplasts. Additionally, the formed chloroplast chains were controllably transported inside the living cells. The optical force exerted on the chloroplasts was calculated to explain the experimental results. This method provides a flexible method for studying intracellular organelle interaction with highly organized organelle-organelle contact in vivo in a non-contact manner.

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

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


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

  17. A filter microplate assay for quantitative analysis of DNA binding proteins using fluorescent DNA. (United States)

    Yang, William C; Swartz, James R


    We present a rapid method for quantifying the apparent DNA binding affinity and capacity of recombinant transcription factors (TFs). We capture His6-tagged TFs using nickel-nitrilotriacetic acid (Ni-NTA) agarose and incubate the immobilized TFs with fluorescently labeled cognate DNA probes. After washing, the strength of the fluorescence signal indicates the extent of DNA binding. The assay was validated using two pluripotency-regulating TFs: SOX2 and NANOG. Using competitive binding analysis with nonlabeled competitor DNA, we show that SOX2 and NANOG specifically bind to their consensus sequences. We also determined the apparent affinity of SOX2 and NANOG for their consensus sequences to be 54.2±9 and 44.0±6nM, respectively, in approximate agreement with literature values. Our assay does not require radioactivity, but radioactively labeling the TFs enables the measurement of absolute amounts of immobilized SOX2 and NANOG and, hence, a DNA-to-protein binding ratio. SOX2 possesses a 0.95 DNA-to-protein binding ratio, whereas NANOG possesses a 0.44 ratio, suggesting that most of the SOX2 and approximately half of the NANOG are competent for DNA binding. Alternatively, the NANOG dimer may be capable of binding only one DNA target. This flexible DNA binding assay enables the analysis of crude or purified samples with or without radioactivity.

  18. Estimation of Residential Heat Pump Consumption for Flexibility Market Applications

    DEFF Research Database (Denmark)

    Kouzelis, Konstantinos; Tan, Zheng-Hua; Bak-Jensen, Birgitte


    load of a flexible device, namely a Heat Pump (HP), out of the aggregated energy consumption of a house. The main idea for accomplishing this, is a comparison of the flexible consumer with electrically similar non-flexible consumers. The methodology is based on machine learning techniques, probability...

  19. A Clearinghouse Concept for Distribution-Level Flexibility Services

    DEFF Research Database (Denmark)

    Heussen, Kai; Bondy, Daniel Esteban Morales; Hu, Junjie;


    Flexibility resources on the demand side are anticipated to become a valuable asset for balancing renewable energy fluctuation as well as for reducing investment needs in distribution grids. To harvest this flexibility for distribution grids, flexibility services need to be defined that can...

  20. Flexible automation and the loss of pooling synergy

    NARCIS (Netherlands)

    Slomp, Jannes; Zee, Durk-Jouke van der


    This paper focuses on the effects of flexible automation on the performance of a job shop. Flexible automated machines may significantly improve the delivery performance and the flow time of jobs. The insertion of a flexible automated system in a job shop, however, also has a counter effect on the m

  1. 75 FR 34445 - Audit Program for Texas Flexible Permit Holders (United States)


    ... AGENCY Audit Program for Texas Flexible Permit Holders AGENCY: Environmental Protection Agency (EPA). ACTION: Notice of Clean Air Act voluntary compliance audit program for flexible permit holders in the State of Texas; request for public comment. SUMMARY: EPA is offering holders of Texas flexible...

  2. Evaluating the Value of Flexibility in Energy Regulation Markets

    DEFF Research Database (Denmark)

    Neupane, Bijay; Pedersen, Torben Bach; Thiesson, Bo


    prices. Further, we analyze the benefit for various types of flexibility and market objectives, to detect the type of energy flexibility that maximizes the benefits. Results show that if 3.87% of total demand is flexible, market can reduce the regulation cost by 49% and the regulation volume by 29.4%....

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

    Directory of Open Access Journals (Sweden)

    Sachiko eTakahama


    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.

  4. Effect of DNA binding on geminate CO recombination kinetics in CooA (United States)

    Benabbas, Abdelkrim; Karunakaran, Venugopal; Youn, Hwan; Poulos, Thomas; Champion, Paul


    CooA proteins are heme-based CO-sensing transcription factors. Here we study the ultrafast dynamics of geminate CO rebinding to RrCooA. The effects of DNA binding and the truncation of the DNA binding domain on the CO geminate recombination kinetics were investigated. The CO rebinding kinetics in these CooA complexes takes place on ultrafast timescales but remains non-exponential over many decades in time. We show that this non-exponential kinetic response is due to a quenched enthalpic barrier distribution resulting from a distribution of heme geometries that is frozen or slowly evolving on the timescale of CO rebinding. We also show that, upon CO binding, the distal pocket of the heme in RrCooA relaxes to form a very efficient hydrophobic trap for CO. DNA binding further tightens the narrow distal pocket and slightly weakens the iron-proximal histidine bond. Analysis of our data reveals that the uncomplexed and inherently flexible DNA binding domain adds additional structural heterogeneity to the heme doming coordinate. When CooA forms a complex with DNA, the flexibility of the DNA-binding domain decreases and the distribution of the conformations available in the heme domain becomes restricted.

  5. Applying flexible molecular docking to simulate protein retention behavior in hydrophobic interaction chromatography

    Institute of Scientific and Technical Information of China (English)

    ZHOU; Peng; TIAN; FeiFei; LI; ZhiLiang


    Interaction between proteins and stationary phase in hydrophobic interaction chromatography (HIC) is differentiated into two thermodynamic processes involving direct nonbonding/conformation interaction and surface hydrophobic effect of proteins, hence quantitatively giving rise to a binary linear relation between HIC retention time (RT) at concentrated salting liquid and ligand-protein binding free energy. Then, possible binding manners for 27 proteins of known crystal structures with hydrophobic ligands are simulated and analyzed via ICM flexible molecular docking and genetic algorithm, with results greatly consistent with experimental values. By investigation, it is confirmed local hydrophobic effects of proteins and nonbinding/conformation interaction between ligand and protein both notably influence HIC chromatogram retention behaviors, mainly focusing on exposed portions on the protein surface.

  6. The Selective Autophagy Receptor p62 Forms a Flexible Filamentous Helical Scaffold

    Directory of Open Access Journals (Sweden)

    Rodolfo Ciuffa


    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.

  7. Crystal structures of the ligand-binding region of uPARAP

    DEFF Research Database (Denmark)

    Yuan, Cai; Jürgensen, Henrik J; Engelholm, Lars H;


    remodelling through interaction with its ligands, including collagens and urokinase plasminogen activator receptor (uPAR). We report the crystal structures of the first four domains of uPARAP (also named the ligand-binding region, LBR) at pH 7.4 in Ca(2+)-bound and Ca(2+)-free forms. The first domain....... These LLRs undergo a Ca(2+)-dependent conformational change, and this is likely to be the key structural determinant affecting the overall conformation of uPARAP. Our results provide a molecular mechanism to support the structural flexibility of uPARAP, and shed light on the structural flexibility of other...

  8. Co-crystallization with conformation-specific designed ankyrin repeat proteins explains the conformational flexibility of BCL-W. (United States)

    Schilling, Johannes; Schöppe, Jendrik; Sauer, Evelyn; Plückthun, Andreas


    BCL-W is a member of the BCL-2 family of anti-apoptotic proteins. A key event in the regulation of apoptosis is the heterodimerization between anti-apoptotic and pro-apoptotic family members, which involves a conserved surface-exposed groove on the anti-apoptotic proteins. Crystal structures of the ligand binding-competent conformation exist for all anti-apoptotic family members, with the exception of BCL-W, due to the flexibility of the BCL-W groove region. Existing structures had suggested major deviations of the BCL-W groove region from the otherwise structurally highly related remaining anti-apoptotic family members. To capture its ligand binding-competent conformation by counteracting the conformational flexibility of the BCL-W groove, we had selected high-affinity groove-binding designed ankyrin repeat proteins (DARPins) using ribosome display. We now determined two high-resolution crystal structures of human BCL-W in complex with different DARPins at resolutions 1.5 and 1.85Å, in which the structure of BCL-W is virtually identical, and BCL-W adopts a conformation extremely similar to the ligand-free conformation of its closest relative BCL-XL in both structures. However, distinct differences to all previous BCL-W structures are evident, notably in the ligand-binding region. We provide the first structural explanation for the conformational flexibility of the BCL-W groove region in comparison to other BCL-2 family members. Due to the importance of the anti-apoptotic BCL-2 family as drug targets, the presented crystal structure of ligand binding-competent BCL-W may serve as a valuable basis for structure-based drug design in the future and provides a missing piece for the structural characterization of this protein family.

  9. Microscopic insight into role of protein flexibility during ion exchange chromatography by nuclear magnetic resonance and quartz crystal microbalance approaches. (United States)

    Hao, Dongxia; Ge, Jia; Huang, Yongdong; Zhao, Lan; Ma, Guanghui; Su, Zhiguo


    Driven by the prevalent use of ion exchange chromatography (IEC) for polishing therapeutic proteins, many rules have been formulated to summarize the different dependencies between chromatographic data and various operational parameters of interest based on statically determined interactions. However, the effects of the unfolding of protein structures and conformational stability are not as well understood. This study focuses on how the flexibility of proteins perturbs retention behavior at the molecular scale using microscopic characterization approaches, including hydrogen-deuterium (H/D) exchange detected by NMR and a quartz crystal microbalance (QCM). The results showed that a series of chromatographic retention parameters depended significantly on the adiabatic compressibility and structural flexibility of the protein. That is, softer proteins with higher flexibility tended to have longer retention times and stronger affinities on SP Sepharose adsorbents. Tracing the underlying molecular mechanism using NMR and QCM indicated that an easily unfolded flexible protein with a more compact adsorption layer might contribute to the longer retention time on adsorbents. The use of NMR and QCM provided a previously unreported approach for elucidating the effect of protein structural flexibility on binding in IEC systems.

  10. Judgement of Design Scheme Based on Flexible Constraint in ICAD

    Institute of Scientific and Technical Information of China (English)


    The conception of flexible constraint is proposed in the paper. The solution of flexible constraint is in special range, and maybe different in different instances of same design scheme. The paper emphasis on how to evaluate and optimize a design scheme with flexible constraints based on the satisfaction degree function defined on flexible constraints. The conception of flexible constraint is used to solve constraint conflict and design optimization in complicated constraint-based assembly design by the PFM parametrization assembly design system. An instance of gear-box design is used for verifying optimization method.

  11. Formation of technical requirements for flexible rotary machine nodes (United States)

    Bulenkov, Y.; Mikhaylov, A.


    The method of parameters determining for the flexible rotary machines and lines and its individual components is described in this article. The method is based on the analysis of the fail safe performance probability. It allows determining the fail safe performance probability for tools, transportation and tool changing device nodes, elements of flexible rotary machine and is based on the analysis of flexible rotor line structure. The relationships between rational flexible rotary line structure and parameters of the individual nodes are shown on the flexible rotor line for the screws processing.

  12. Control of a Lightweight Flexible Robotic Arm Using Sliding Modes

    Directory of Open Access Journals (Sweden)

    Ibone Lizarraga


    Full Text Available This paper presents a robust control scheme for flexible link robotic manipulators, which is based on considering the flexible mechanical structure as a system with slow (rigid and fast (flexible modes that can be controlled separately. The rigid dynamics is controlled by means of a robust sliding-mode approach with wellestablished stability properties while an LQR optimal design is adopted for the flexible dynamics. Experimental results show that this composite approach achieves good closed loop tracking properties both for the rigid and the flexible dynamics.

  13. Increasing importance of protein flexibility in designing biocatalytic processes

    Directory of Open Access Journals (Sweden)

    Joyeeta Mukherjee


    Full Text Available Enzymes require some flexibility for catalysis. Biotechnologists prefer stable enzymes but often this stabilization comes at the cost of reduced efficiency. Enzymes from thermophiles have low flexibility but poor catalytic rates. Enzymes from psychrophiles are less stable but show good catalytic rates at low temperature. In organic solvents enzymes perform poorly as the prior drying makes the enzyme molecules very rigid. Adding water or increasing reaction temperature improves flexibility and catalytic rates. In case of hydrolases, flexibility and enantioselectivity have interdependence. Understanding the complex role of protein flexibility in biocatalysis can help in designing biotechnological processes.

  14. Origin of Metastable Knots in Single Flexible Chains (United States)

    Dai, Liang; Renner, C. Benjamin; Doyle, Patrick S.


    Recent theoretical progress has explained the physics of knotting of semiflexible polymers, yet knotting of flexible polymers is relatively unexplored. We herein develop a new theory for the size distribution of knots on a flexible polymer and the existence of metastable knots. We show the free energy of a flexible molecule in a tube can be mapped to quantitatively reproduce the free energy distribution of a knot on a flexible chain. The size distribution of knots on flexible chains is expected to be universal and might be observed at a macroscopic scale, such as a string of hard balls.

  15. Binding Mechanisms of Intrinsically Disordered Proteins: Theory, Simulation, and Experiment (United States)

    Mollica, Luca; Bessa, Luiza M.; Hanoulle, Xavier; Jensen, Malene Ringkjøbing; Blackledge, Martin; Schneider, Robert


    In recent years, protein science has been revolutionized by the discovery of intrinsically disordered proteins (IDPs). In contrast to the classical paradigm that a given protein sequence corresponds to a defined structure and an associated function, we now know that proteins can be functional in the absence of a stable three-dimensional structure. In many cases, disordered proteins or protein regions become structured, at least locally, upon interacting with their physiological partners. Many, sometimes conflicting, hypotheses have been put forward regarding the interaction mechanisms of IDPs and the potential advantages of disorder for protein-protein interactions. Whether disorder may increase, as proposed, e.g., in the “fly-casting” hypothesis, or decrease binding rates, increase or decrease binding specificity, or what role pre-formed structure might play in interactions involving IDPs (conformational selection vs. induced fit), are subjects of intense debate. Experimentally, these questions remain difficult to address. Here, we review experimental studies of binding mechanisms of IDPs using NMR spectroscopy and transient kinetic techniques, as well as the underlying theoretical concepts and numerical methods that can be applied to describe these interactions at the atomic level. The available literature suggests that the kinetic and thermodynamic parameters characterizing interactions involving IDPs can vary widely and that there may be no single common mechanism that can explain the different binding modes observed experimentally. Rather, disordered proteins appear to make combined use of features such as pre-formed structure and flexibility, depending on the individual system and the functional context. PMID:27668217

  16. Differential Binding Models for Direct and Reverse Isothermal Titration Calorimetry. (United States)

    Herrera, Isaac; Winnik, Mitchell A


    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.

  17. Flexible energy-storage devices: design consideration and recent progress. (United States)

    Wang, Xianfu; Lu, Xihong; Liu, Bin; Chen, Di; Tong, Yexiang; Shen, Guozhen


    Flexible energy-storage devices are attracting increasing attention as they show unique promising advantages, such as flexibility, shape diversity, light weight, and so on; these properties enable applications in portable, flexible, and even wearable electronic devices, including soft electronic products, roll-up displays, and wearable devices. Consequently, considerable effort has been made in recent years to fulfill the requirements of future flexible energy-storage devices, and much progress has been witnessed. This review describes the most recent advances in flexible energy-storage devices, including flexible lithium-ion batteries and flexible supercapacitors. The latest successful examples in flexible lithium-ion batteries and their technological innovations and challenges are reviewed first. This is followed by a detailed overview of the recent progress in flexible supercapacitors based on carbon materials and a number of composites and flexible micro-supercapacitors. Some of the latest achievements regarding interesting integrated energy-storage systems are also reviewed. Further research direction is also proposed to surpass existing technological bottle-necks and realize idealized flexible energy-storage devices.

  18. Evaluation of flexibility in FMS using SAW and WPM

    Directory of Open Access Journals (Sweden)

    Vineet Jain


    Full Text Available The evaluation of the most appropriate flexibility in the manufacturing sector is one of the strategic issues that may affect the Flexibile Manufacturing System (FMS. In this paper, a Multiple Attribute Decision Making Method (MADM methodology is structured to resolve this problem. The two decision making methods, which are Simple Additive Weighting (SAW and Weighted Product Method (WPM, are integrated with Analytical hierarchy process (AHP in order to get the best use of information available. The aim of using AHP is to give the weights of the attributes and these weights are used in SAW & WPM method for ranking of flexibility in FMS. Furthermore, the method uses fuzzy logic to change the qualitative attributes into the quantitative attributes. 15 factors are taken to evaluation of 15 flexibility. In this report, we concluded that Product Flexibility has the most impact in 15 flexibilities and Programme Flexibility has the least impact in these 15 flexibilities by this methodology.

  19. Indirect control of flexible demand for power system applications

    DEFF Research Database (Denmark)

    Sossan, Fabrizio

    Flexhouse, a facility of DTU Elektro for testing demand side management strategies, as experimental site. In the latter case, we develop four applications where flexible demand is required to support power system operations. The applications are: integration of the operation of flexible demand......This thesis addresses the topic of control of flexible demand to provide support to the operation of the electric power system. We focus on the indirect control approach, a framework that enables demand response by means of a consumption incentive signal. Initially, the concept of flexibility...... is defined and a classification of flexible electric loads is presented. In order to evaluate the potential of flexible demand, the storage capacity associated with the operation of a number domestic electric loads is quantified by means of simulations. Subsequently, the topic of indirect control of flexible...

  20. A Partial Calcium-Free Linker Confers Flexibility to Inner-Ear Protocadherin-15. (United States)

    Powers, Robert E; Gaudet, Rachelle; Sotomayor, Marcos


    Tip links of the inner ear are protein filaments essential for hearing and balance. Two atypical cadherins, cadherin-23 and protocadherin-15, interact in a Ca(2+)-dependent manner to form tip links. The largely unknown structure and mechanics of these proteins are integral to understanding how tip links pull on ion channels to initiate sensory perception. Protocadherin-15 has 11 extracellular cadherin (EC) repeats. Its EC3-4 linker lacks several of the canonical Ca(2+)-binding residues, and contains an aspartate-to-alanine polymorphism (D414A) under positive selection in East Asian populations. We present structures of protocadherin-15 EC3-5 featuring two Ca(2+)-binding linker regions: canonical EC4-5 linker binding three Ca(2+) ions, and non-canonical EC3-4 linker binding only two Ca(2+) ions. Our structures and biochemical assays reveal little difference between the D414 and D414A variants. Simulations predict that the partial Ca(2+)-free EC3-4 linker exhibits increased flexural flexibility without compromised mechanical strength, providing insight into the dynamics of tip links and other atypical cadherins.