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Sample records for extracellular loops els

  1. Extracellular matrix proteins: A positive feedback loop in lung fibrosis?

    NARCIS (Netherlands)

    Blaauboer, M.E.; Boeijen, F.R.; Emson, C.L.; Turner, S.M.; Zandieh-Doulabi, B.; Hanemaaijer, R.; Smit, T.H.; Stoop, R.; Everts, V.

    2014-01-01

    Lung fibrosis is characterized by excessive deposition of extracellular matrix. This not only affects tissue architecture and function, but it also influences fibroblast behavior and thus disease progression. Here we describe the expression of elastin, type V collagen and tenascin C during the

  2. Importance of the Extracellular Loop 4 in the Human Serotonin Transporter for Inhibitor Binding and Substrate Translocation

    DEFF Research Database (Denmark)

    Rannversson, Hafsteinn; Wilson, Pamela; Kristensen, Kristina

    2015-01-01

    is connected to both sides of the membrane by permeation pathways, of which only one is accessible at a time. The coordinated conformational changes in SERT associated with substrate translocation are not fully understood. Here, we have identified a Leu to Glu mutation at position 406 (L406E......) in the extracellular loop 4 (EL4) of human SERT, which induced a remarkable gain-of-potency (up to >40-fold) for a range of SERT inhibitors. The effects were highly specific for L406E relative to six other mutations in the same position, including the closely related L406D mutation, showing that the effects induced...

  3. Carbenoxolone inhibits Pannexin1 channels through interactions in the first extracellular loop.

    Science.gov (United States)

    Michalski, Kevin; Kawate, Toshimitsu

    2016-02-01

    Pannexin1 (Panx1) is an ATP release channel important for controlling immune responses and synaptic strength. Various stimuli including C-terminal cleavage, a high concentration of extracellular potassium, and voltage have been demonstrated to activate Panx1. However, it remains unclear how Panx1 senses and integrates such diverse stimuli to form an open channel. To provide a clue on the mechanism underlying Panx1 channel gating, we investigated the action mechanism of carbenoxolone (CBX), the most commonly used small molecule for attenuating Panx1 function triggered by a wide range of stimuli. Using a chimeric approach, we discovered that CBX reverses its action polarity and potentiates the voltage-gated channel activity of Panx1 when W74 in the first extracellular loop is mutated to a nonaromatic residue. A systematic mutagenesis study revealed that conserved residues in this loop also play important roles in CBX function, potentially by mediating CBX binding. We extended our experiments to other Panx1 inhibitors such as probenecid and ATP, which also potentiate the voltage-gated channel activity of a Panx1 mutant at position 74. Notably, probenecid alone can activate this mutant at a resting membrane potential. These data suggest that CBX and other inhibitors, including probenecid, attenuate Panx1 channel activity through modulation of the first extracellular loop. Our experiments are the first step toward identifying a previously unknown mode of CBX action, which provide insight into the role of the first extracellular loop in Panx1 channel gating.

  4. Importance of the extracellular loops in G protein-coupled receptors for ligand recognition and receptor activation.

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    Peeters, M C; van Westen, G J P; Li, Q; IJzerman, A P

    2011-01-01

    G protein-coupled receptors (GPCRs) are the major drug target of medicines on the market today. Therefore, much research is and has been devoted to the elucidation of the function and three-dimensional structure of this large family of membrane proteins, which includes multiple conserved transmembrane domains connected by intra- and extracellular loops. In the last few years, the less conserved extracellular loops have garnered increasing interest, particularly after the publication of several GPCR crystal structures that clearly show the extracellular loops to be involved in ligand binding. This review will summarize the recent progress made in the clarification of the ligand binding and activation mechanism of class-A GPCRs and the role of extracellular loops in this process.

  5. Micellar lipid composition affects micelle interaction with class B scavenger receptor extracellular loops.

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    Goncalves, Aurélie; Gontero, Brigitte; Nowicki, Marion; Margier, Marielle; Masset, Gabriel; Amiot, Marie-Josèphe; Reboul, Emmanuelle

    2015-06-01

    Scavenger receptors (SRs) like cluster determinant 36 (CD36) and SR class B type I (SR-BI) play a debated role in lipid transport across the intestinal brush border membrane. We used surface plasmon resonance to analyze real-time interactions between the extracellular protein loops and various ligands ranging from single lipid molecules to mixed micelles. Micelles mimicking physiological structures were necessary for optimal binding to both the extracellular loop of CD36 (lCD36) and the extracellular loop of SR-BI (lSR-BI). Cholesterol, phospholipid, and fatty acid micellar content significantly modulated micelle binding to and dissociation from the transporters. In particular, high phospholipid micellar concentrations inhibited micelle binding to both receptors (-53.8 and -74.4% binding at 0.32 mM compared with 0.04 mM for lCD36 and lSR-BI, respectively, P < 0.05). The presence of fatty acids was crucial for micelle interactions with both proteins (94.4 and 81.3% binding with oleic acid for lCD36 and lSR-BI, respectively, P < 0.05) and fatty acid type substitution within the micelles was the component that most impacted micelle binding to the transporters. These effects were partly due to subsequent modifications in micellar size and surface electric charge, and could be correlated to micellar vitamin D uptake by Caco-2 cells. Our findings show for the first time that micellar lipid composition and micellar properties are key factors governing micelle interactions with SRs.

  6. Cataracts and microphthalmia caused by a Gja8 mutation in extracellular loop 2.

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    Chun-Hong Xia

    Full Text Available The mouse semi-dominant Nm2249 mutation displays variable cataracts in heterozygous mice and smaller lenses with severe cataracts in homozygous mice. This mutation is caused by a Gja8(R205G point mutation in the second extracellular loop of the Cx50 (or α8 connexin protein. Immunohistological data reveal that Cx50-R205G mutant proteins and endogenous wild-type Cx46 (or α3 connexin proteins form diffuse tiny spots rather than typical punctate signals of normal gap junctions in the lens. The level of phosphorylated Cx46 proteins is decreased in Gja8(R205G/R205G mutant lenses. Genetic analysis reveals that the Cx50-R205G mutation needs the presence of wild-type Cx46 to disrupt lens peripheral fibers and epithelial cells. Electrophysiological data in Xenopus oocytes reveal that Cx50-R205G mutant proteins block channel function of gap junctions composed of wild-type Cx50, but only affect the gating of wild-type Cx46 channels. Both genetic and electrophysiological results suggest that Cx50-R205G mutant proteins alone are unable to form functional channels. These findings imply that the Gja8(R205G mutation differentially impairs the functions of Cx50 and Cx46 to cause cataracts, small lenses and microphthalmia. The Gja8(R205G mutation occurs at the same conserved residue as the human GJA8(R198W mutation. This work provides molecular insights to understand the cataract and microphthalmia/microcornea phenotype caused by Gja8 mutations in mice and humans.

  7. Cataracts and microphthalmia caused by a Gja8 mutation in extracellular loop 2.

    Science.gov (United States)

    Xia, Chun-Hong; Chang, Bo; Derosa, Adam M; Cheng, Catherine; White, Thomas W; Gong, Xiaohua

    2012-01-01

    The mouse semi-dominant Nm2249 mutation displays variable cataracts in heterozygous mice and smaller lenses with severe cataracts in homozygous mice. This mutation is caused by a Gja8(R205G) point mutation in the second extracellular loop of the Cx50 (or α8 connexin) protein. Immunohistological data reveal that Cx50-R205G mutant proteins and endogenous wild-type Cx46 (or α3 connexin) proteins form diffuse tiny spots rather than typical punctate signals of normal gap junctions in the lens. The level of phosphorylated Cx46 proteins is decreased in Gja8(R205G/R205G) mutant lenses. Genetic analysis reveals that the Cx50-R205G mutation needs the presence of wild-type Cx46 to disrupt lens peripheral fibers and epithelial cells. Electrophysiological data in Xenopus oocytes reveal that Cx50-R205G mutant proteins block channel function of gap junctions composed of wild-type Cx50, but only affect the gating of wild-type Cx46 channels. Both genetic and electrophysiological results suggest that Cx50-R205G mutant proteins alone are unable to form functional channels. These findings imply that the Gja8(R205G) mutation differentially impairs the functions of Cx50 and Cx46 to cause cataracts, small lenses and microphthalmia. The Gja8(R205G) mutation occurs at the same conserved residue as the human GJA8(R198W) mutation. This work provides molecular insights to understand the cataract and microphthalmia/microcornea phenotype caused by Gja8 mutations in mice and humans.

  8. A second disulfide bridge from the N-terminal domain to extracellular loop 2 dampens receptor activity in GPR39

    DEFF Research Database (Denmark)

    Storjohann, Laura; Holst, Birgitte; Schwartz, Thue W

    2008-01-01

    A highly conserved feature across all families of 7TM receptors is a disulfide bridge between a Cys residue located at the extracellular end of transmembrane segment III (TM-III) and one in extracellular loop 2 (ECL-2). The zinc sensor GPR39 contains four Cys residues in the extracellular domains....... By using mutagenesis, treatment with the reducing agent TCEP, and a labeling procedure for free sulfhydryl groups, we identify the pairing of these Cys residues in two disulfide bridges: the prototypical bridge between Cys (108) in TM-III and Cys (210) in ECL-2 and a second disulfide bridge connecting Cys...... (11) in the N-terminal domain with Cys (191) in ECL-2. Disruption of the conserved disulfide bond by mutagenesis greatly reduced the level of cell surface expression and eliminated agonist-induced increases in inositol phosphate production but surprisingly enhanced constitutive signaling. Disruption...

  9. Large extracellular loop of tetraspanin as a potential vaccine candidate for filariasis.

    Directory of Open Access Journals (Sweden)

    Gajalakshmi Dakshinamoorthy

    Full Text Available Lymphatic filariasis affects nearly 120 million people worldwide and mass preventive chemotherapy is currently used as a strategy to control this infection. This has substantially reduced the incidence of the infection in several parts of the world. However, a prophylactic vaccine would be more effective in preventing future infections and will supplement the mass chemotherapy efforts. Unfortunately, there is no licensed vaccine available currently to prevent this infection. Molecules expressed on the surface of the parasite are potential candidates for vaccine development as they are exposed to the host immune system. In this study we show that the large extracellular loop of tetraspanin (TSP LEL, a protein expressed on the cuticle of Brugia malayi and Wuchereria bancrofti is a potential vaccine candidate. Our results showed that BmTSP LEL is expressed on the surface of B. malayi infective third stage larvae (L3 and sera from human subjects who are putatively immune to lymphatic filariasis carry high titer of IgG1 and IgG3 antibodies against BmTSP LEL and WbTSP LEL. We also showed that these antibodies in the sera of human subjects can participate in the killing of B. malayi L3 in an antibody dependent cell-mediated cytotoxicity mechanism. Vaccination trials in mice showed that close to 64% protection were achieved against challenge infections with B. malayi L3. Immunized animals showed high titer of anti-WbTSP LEL IgG1, IgG2a and IgG2b antibodies in the sera and IFN-γ secreting cells in the spleen. Onchocerca volvulus another filarial parasite also expresses TSP LEL. Cross-reactivity studies showed that IgG1 antibody in the sera of endemic normal subjects, recognize OvTSP LEL. Similarly, anti-OvTSP LEL antibodies in the sera of subjects who are immune to O. volvulus were also shown to cross-react with rWbTSP LEL and rBmTSP LEL. These findings thus suggested that rTSP LEL can be developed as a potential vaccine candidate against multiple

  10. Interaction between 2 extracellular loops influences the activity of the cystic fibrosis transmembrane conductance regulator chloride channel.

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    Broadbent, Steven D; Wang, Wuyang; Linsdell, Paul

    2014-10-01

    Activity of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel is thought to be controlled by cytoplasmic factors. However, recent evidence has shown that overall channel activity is also influenced by extracellular anions that interact directly with the extracellular loops (ECLs) of the CFTR protein. Very little is known about the structure of the ECLs or how substances interacting with these ECLs might affect CFTR function. We used patch-clamp recording to investigate the accessibility of cysteine-reactive reagents to cysteines introduced throughout ECL1 and 2 key sites in ECL4. Furthermore, interactions between ECL1 and ECL4 were investigated by the formation of disulfide crosslinks between cysteines introduced into these 2 regions. Crosslinks could be formed between R899C (in ECL4) and a number of sites in ECL1 in a manner that was dependent on channel activity, suggesting that the relative orientation of these 2 loops changes on activation. Formation of these crosslinks inhibited channel function, suggesting that relative movement of these ECLs is important to normal channel function. Implications of these findings for the effects of mutations in the ECLs that are associated with cystic fibrosis and interactions with extracellular substances that influence channel activity are discussed.

  11. Colicins U and Y inhibit growth of Escherichia coli strains via recognition of conserved OmpA extracellular loop 1.

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    Bosák, Juraj; Micenková, Lenka; Doležalová, Magda; Šmajs, David

    2016-11-01

    Interactions of colicins U and Y with the OmpA (Outer membrane protein A) receptor molecule were studied using site-directed mutagenesis and colicin binding assay. A systematic mutagenesis of the colicin-susceptible OmpA sequence from Escherichia coli (OmpAEC) to the colicin-resistant OmpA sequence from Serratia marcescens (OmpASM) was performed in regions corresponding to extracellular OmpA loops 1-4. Susceptibility to colicins U and Y was significantly affected by the OmpA mutation in loop 1. As with functional analysis, a decrease in binding capacity of His-tagged colicin U was found for recombinant OmpA with a mutated segment in loop 1 compared to control OmpAEC. To verify the importance of the identified amino acid residues in OmpA loop 1, we introduced loop 1 from OmpAEC into OmpASM, which resulted in the substantial increase of susceptibility to colicins U and Y. In addition, colicins U and Y were tested against a panel of 118 bacteriocin non-producing strains of four Escherichia species, including E. coli (39 strains), E. fergusonii (10 strains), E. hermannii (42 strains), and E. vulneris (27 strains). A majority (82%) of E. coli strains was susceptible to colicins U and Y. Interestingly, colicins U and Y also inhibited all of the 30 tested multidrug-resistant E. coli O25b-ST131 isolates. These findings, together with the fact that OmpA loop 1 is important for bacterial virulence and is evolutionary conserved, offer the potential of using colicins U and Y as specific anti-OmpA loop 1 directed antibacterial proteins.

  12. Interaction of hepatitis C virus envelope glycoprotein E2 with the large extracellular loop of tupaia CD81

    Institute of Scientific and Technical Information of China (English)

    Zhan-Fei Tian; Hong Shen; Xi-Hua Fu; Yi-Chun Chen; Hubert E Blum; Thomas F Baumert; Xi-Ping Zhao

    2009-01-01

    AIM: To further analyze the interaction of tupaia CD81 with hepatitis C virus (HCV) envelope protein E2. METHODS: A tupaia CD81 large extracellular loop (CD81 LEL), which binds to HCV E2 protein, was cloned and expressed as a GST-fusion protein, and interaction of HCV E2 protein with a tupaia CD81 LEL was evaluated by enzyme-linked immunosorbent assay (EIA). RESULTS: Although tupaia and human CD81 LEL differed in 6 amino acid changes, tupaia CD81 LEL was strongly recognized by anti-CD81 antibodies against human CD81 LEL conformation-dependent epitopes. Investigating LEL CD81-E2 interactions by EIA, we demonstrated that binding of tupaia CD81 LEL GST fusion protein to recombinant HCV E2 protein was markedly reduced compared to binding of human CD81 LEL GST fusion protein to recombinant HCV E2 protein. CONCLUSION: These data suggest that the structural differences in-between the tupaia and human CD81 may alter the interaction of the large extracellular loop with HCV envelope glycoprotein E2. These findings may be important for the understanding of the mechanisms of binding and entry of HCV to PTHs.

  13. A feed-forward loop coupling extracellular BMP transport and morphogenesis in Drosophila wing.

    Directory of Open Access Journals (Sweden)

    Shinya Matsuda

    2013-03-01

    Full Text Available A variety of extracellular factors regulate morphogenesis during development. However, coordination between extracellular signaling and dynamic morphogenesis is largely unexplored. We address the fundamental question by studying posterior crossvein (PCV development in Drosophila as a model, in which long-range BMP transport from the longitudinal veins plays a critical role during the pupal stages. Here, we show that RhoGAP Crossveinless-C (Cv-C is induced at the PCV primordial cells by BMP signaling and mediates PCV morphogenesis cell-autonomously by inactivating members of the Rho-type small GTPases. Intriguingly, we find that Cv-C is also required non-cell-autonomously for BMP transport into the PCV region, while a long-range BMP transport is guided toward ectopic wing vein regions by loss of the Rho-type small GTPases. We present evidence that low level of ß-integrin accumulation at the basal side of PCV epithelial cells regulated by Cv-C provides an optimal extracellular environment for guiding BMP transport. These data suggest that BMP transport and PCV morphogenesis are tightly coupled. Our study reveals a feed-forward mechanism that coordinates the spatial distribution of extracellular instructive cues and morphogenesis. The coupling mechanism may be widely utilized to achieve precise morphogenesis during development and homeostasis.

  14. An ion selectivity filter in the extracellular domain of Cys-loop receptors reveals determinants for ion conductance.

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    Hansen, Scott B; Wang, Hai-Long; Taylor, Palmer; Sine, Steven M

    2008-12-26

    Neurotransmitter binding to Cys-loop receptors promotes a prodigious transmembrane flux of several million ions/s, but to date, structural determinants of ion flux have been identified flanking the membrane-spanning region. Using x-ray crystallography, sequence analysis, and single-channel recording, we identified a novel determinant of ion conductance near the point of entry of permeant ions. Co-crystallization of acetylcholine-binding protein with sulfate anions revealed coordination of SO4(2-) with a ring of lysines at a position equivalent to 24 A above the lipid membrane in homologous Cys-loop receptors. Analysis of multiple sequence alignments revealed that residues equivalent to the ring of lysines are negatively charged in cation-selective receptors but are positively charged in anion-selective receptors. Charge reversal of side chains at homologous positions in the nicotinic receptor from the motor end plate decreases unitary conductance up to 80%. Selectivity filters stemming from transmembrane alpha-helices have similar pore diameters and compositions of amino acids. These findings establish that when the channel opens under a physiological electrochemical gradient, permeant ions are initially stabilized within the extracellular vestibule of Cys-loop receptors, and this stabilization is a major determinant of ion conductance.

  15. Structure of a C. perfringens enterotoxin mutant in complex with a modified Claudin-2 extracellular loop 2.

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    Yelland, Tamas S; Naylor, Claire E; Bagoban, Tannya; Savva, Christos G; Moss, David S; McClane, Bruce A; Blasig, Ingolf E; Popoff, M; Basak, Ajit K

    2014-09-09

    CPE (Clostridium perfringens enterotoxin) is the major virulence determinant for C. perfringens type-A food poisoning, the second most common bacterial food-borne illness in the UK and USA. After binding to its receptors, which include particular human claudins, the toxin forms pores in the cell membrane. The mature pore apparently contains a hexamer of CPE, claudin and, possibly, occludin. The combination of high binding specificity with cytotoxicity has resulted in CPE being investigated, with some success, as a targeted cytotoxic agent for oncotherapy. In this paper, we present the X-ray crystallographic structure of CPE in complex with a peptide derived from extracellular loop 2 of a modified, CPE-binding Claudin-2, together with high-resolution native and pore-formation mutant structures. Our structure provides the first atomic-resolution data on any part of a claudin molecule and reveals that claudin's CPE-binding fingerprint (NPLVP) is in a tight turn conformation and binds, as expected, in CPE's C-terminal claudin-binding groove. The leucine and valine residues insert into the binding groove while the first residue, asparagine, tethers the peptide via an interaction with CPE's aspartate 225 and the two prolines are required to maintain the tight turn conformation. Understanding the structural basis of the contribution these residues make to binding will aid in engineering CPE to target tumor cells.

  16. Conformationally sensitive proximity of extracellular loops 2 and 4 of the γ-aminobutyric acid (GABA) transporter GAT-1 inferred from paired cysteine mutagenesis.

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    Hilwi, Maram; Dayan, Oshrat; Kanner, Baruch I

    2014-12-05

    The sodium- and chloride-coupled GABA transporter GAT-1 is a member of the neurotransmitter:sodium:symporters, which are crucial for synaptic transmission. Structural work on the bacterial homologue LeuT suggests that extracellular loop 4 closes the extracellular solvent pathway when the transporter becomes inward-facing. To test whether this model can be extrapolated to GAT-1, cysteine residues were introduced at positions 359 and 448 of extracellular loop 4 and transmembrane helix 10, respectively. Treatment of HeLa cells, expressing the double cysteine mutant S359C/K448C with the oxidizing reagent copper(II)(1,10-phenantroline)3, resulted in a significant inhibition of [(3)H]GABA transport. However, transport by the single cysteine mutant S359C was also inhibited by the oxidant, whereas its activity was almost 4-fold stimulated by dithiothreitol. Both effects were attenuated when the conserved cysteine residues, Cys-164 and/or Cys-173, were replaced by serine. These cysteines are located in extracellular loop 2, the role of which in the structure and function of the eukaryotic neurotransmitter:sodium:symporters remains unknown. The inhibition of transport of S359C by the oxidant was markedly reduced under conditions expected to increase the proportion of inward-facing transporters, whereas the reactivity of the mutants to a membrane-impermeant sulfhydryl reagent was not conformationally sensitive. Our data suggest that extracellular loops 2 and 4 come into close proximity to each other in the outward-facing conformation of GAT-1.

  17. Detection of aquaporin-4 antibody using aquaporin-4 extracellular loop-based carbon nanotube biosensor for the diagnosis of neuromyelitis optica.

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    Son, Manki; Kim, Daesan; Park, Kyung Seok; Hong, Seunghun; Park, Tai Hyun

    2016-04-15

    Here we propose a carbon nanotube (CNT) field-effect transistor (FET) functionalized with aquaporin-4 (AQP4) extracellular loop peptides for the rapid detection of AQP4 antibody without pretreatment. Neuromyelitis optica (NMO) is a rare disease of the central nerve system that affects the optic nerves and the spinal cord. NMO-IgG, a serum antibody in patients, is highly specific for NMO and targets AQP4. We synthesized AQP4 extracellular loop peptides, known as primary autoimmune target in NMO, and immobilized them onto CNT-FET. The sensor showed p-type FET characteristics after the functionalization of peptides. The sensor was able to detect antibody with a detection limit of 1 ng l(-1). Moreover, AQP4 antibody in human serum was detected without any pretreatment. These results indicate that the biosensor can be used for rapid and simple detection of NMO antibody.

  18. Manipulations of extracellular Loop 2 in α1 GlyR ultra-sensitive ethanol receptors (USERs) enhance receptor sensitivity to isoflurane, ethanol, and lidocaine, but not propofol.

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    Naito, A; Muchhala, K H; Trang, J; Asatryan, L; Trudell, J R; Homanics, G E; Alkana, R L; Davies, D L

    2015-06-25

    We recently developed ultra-sensitive ethanol receptors (USERs) as a novel tool for investigation of single receptor subunit populations sensitized to extremely low ethanol concentrations that do not affect other receptors in the nervous system. To this end, we found that mutations within the extracellular Loop 2 region of glycine receptors (GlyRs) and γ-aminobutyric acid type A receptors (GABAARs) can significantly increase receptor sensitivity to micro-molar concentrations of ethanol resulting in up to a 100-fold increase in ethanol sensitivity relative to wild-type (WT) receptors. The current study investigated: (1) Whether structural manipulations of Loop 2 in α1 GlyRs could similarly increase receptor sensitivity to other anesthetics; and (2) If mutations exclusive to the C-terminal end of Loop 2 are sufficient to impart these changes. We expressed α1 GlyR USERs in Xenopus oocytes and tested the effects of three classes of anesthetics, isoflurane (volatile), propofol (intravenous), and lidocaine (local), known to enhance glycine-induced chloride currents using two-electrode voltage clamp electrophysiology. Loop 2 mutations produced a significant 10-fold increase in isoflurane and lidocaine sensitivity, but no increase in propofol sensitivity compared to WT α1 GlyRs. Interestingly, we also found that structural manipulations in the C-terminal end of Loop 2 were sufficient and selective for α1 GlyR modulation by ethanol, isoflurane, and lidocaine. These studies are the first to report the extracellular region of α1 GlyRs as a site of lidocaine action. Overall, the findings suggest that Loop 2 of α1 GlyRs is a key region that mediates isoflurane and lidocaine modulation. Moreover, the results identify important amino acids in Loop 2 that regulate isoflurane, lidocaine, and ethanol action. Collectively, these data indicate the commonality of the sites for isoflurane, lidocaine, and ethanol action, and the structural requirements for allosteric modulation on

  19. Conserved Aspartic Acid Residues Lining the Extracellular Loop I of Sodium-coupled Bile Acid Transporter ASBT Interact with Na+ and 7α-OH Moieties on the Ligand Cholestane Skeleton*

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    Hussainzada, Naissan; Da Silva, Tatiana Claro; Zhang, Eric Y.; Swaan, Peter W.

    2008-01-01

    Functional contributions of residues Val-99—Ser-126 lining extracellular loop (EL) 1 of the apical sodium-dependent bile acid transporter were determined via cysteine-scanning mutagenesis, thiol modification, and in silico interpretation. Despite membrane expression for all but three constructs (S112C, Y117C, S126C), most EL1 mutants (64%) were inactivated by cysteine mutation, suggesting a functional role during sodium/bile acid co-transport. A negative charge at conserved residues Asp-120 and Asp-122 is required for transport function, whereas neutralization of charge at Asp-124 yields a functionally active transporter. D124A exerts low affinity for common bile acids except deoxycholic acid, which uniquely lacks a 7α-hydroxyl (OH) group. Overall, we conclude that (i) Asp-122 functions as a Na+ sensor, binding one of two co-transported Na+ ions, (ii) Asp-124 interacts with 7α-OH groups of bile acids, and (iii) apolar EL1 residues map to hydrophobic ligand pharmacophore features. Based on these data, we propose a comprehensive mechanistic model involving dynamic salt bridge pairs and hydrogen bonding involving multiple residues to describe sodium-dependent bile acid transporter-mediated bile acid and cation translocation. PMID:18508772

  20. Extended N(6) substitution of rigid C2-arylethynyl nucleosides for exploring the role of extracellular loops in ligand recognition at the A3 adenosine receptor.

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    Tosh, Dilip K; Paoletta, Silvia; Chen, Zhoumou; Moss, Steven M; Gao, Zhan-Guo; Salvemini, Daniela; Jacobson, Kenneth A

    2014-08-01

    2-Arylethynyl-(N)-methanocarba adenosine 5'-methyluronamides containing rigid N(6)-(trans-2-phenylcyclopropyl) and 2-phenylethynyl groups were synthesized as agonists for probing structural features of the A3 adenosine receptor (AR). Radioligand binding confirmed A3AR selectivity and N(6)-1S,2R stereoselectivity for one diastereomeric pair. The environment of receptor-bound, conformationally constrained N(6) groups was explored by docking to an A3AR homology model, indicating specific hydrophobic interactions with the second extracellular loop able to modulate the affinity profile. 2-Pyridylethynyl derivative 18 was administered orally in mice to reduce chronic neuropathic pain in the chronic constriction injury model.

  1. Congenital heart block: identification of autoantibody binding site on the extracellular loop (domain I, S5-S6) of alpha(1D) L-type Ca channel.

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    Karnabi, Eddy; Qu, Yongxia; Wadgaonkar, Raj; Mancarella, Salvatore; Yue, Yuankun; Chahine, Mohamed; Clancy, Robert M; Buyon, Jill P; Boutjdir, Mohamed

    2010-03-01

    Congenital heart block (CHB) is an autoimmune disease associated with autoantibodies against intracellular ribonucleoproteins SSB/La and SSA/Ro. The hallmark of CHB is complete atrioventricular block. We have recently established that anti-SSA/Ro -SSB/La autoantibodies inhibit alpha(1D) L-type Ca current, I(Ca-L), and cross-react with the alpha(1D) Ca channel protein. This study aims at identifying the possible binding sites on alpha(1D) protein for autoantibodies from sera of mothers with CHB children. GST fusion proteins of the extracellular regions between the transmembrane segments (S5-S6) of each of the four alpha(1D) Ca channel protein domains I-IV were prepared and tested for reactivity with sera from mothers with CHB children and controls using ELISA. Sera containing anti-Ro/La autoantibodies from 118 mothers with CHB children and from 15 mothers with anti-Ro/La autoantibodies but have healthy children, and from 28 healthy mothers without anti-Ro/La autoantibodies and healthy children were evaluated. Seventeen of 118 (14.4%) sera from mothers with CHB children reacted with the extracellular loop of domain I S5-S6 region (E1). In contrast, only 2 of 28 (7%) of sera from healthy mothers (-anti-Ro/La) and healthy children reacted with E1 loop and none (0 of 15) of sera from healthy mothers (+anti-Ro/La) and healthy children reacted with the E1 loop. Preincubation of E1 loop with the positive sera decreased the O.D reading establishing the specificity of the response. Electrophysiological characterization of the ELISA positive sera and purified IgG showed inhibition (44.1% and 49.8%, respectively) of the alpha(1D) I(Ca-L) expressed in tsA201 cells. The inhibition was abolished when the sera were pre-incubated with E1 fusion protein. The results identified the extracellular loop of domain I S5-S6 of L-type Ca channel alpha(1D) subunit as a target for autoantibodies from a subset of mothers with CHB children. This novel finding provides insights into the

  2. Extracellular Loop 2 of the Free Fatty Acid Receptor 2 Mediates Allosterism of a Phenylacetamide Ago-Allosteric ModulatorS⃞

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    Smith, Nicola J.; Ward, Richard J.; Stoddart, Leigh A.; Hudson, Brian D.; Kostenis, Evi; Ulven, Trond; Morris, Joanne C.; Tränkle, Christian; Tikhonova, Irina G.; Adams, David R.

    2011-01-01

    Allosteric agonists are powerful tools for exploring the pharmacology of closely related G protein-coupled receptors that have nonselective endogenous ligands, such as the short chain fatty acids at free fatty acid receptors 2 and 3 (FFA2/GPR43 and FFA3/GPR41, respectively). We explored the molecular mechanisms mediating the activity of 4-chloro-α-(1-methylethyl)-N-2-thiazolylbenzeneacetamide (4-CMTB), a recently described phenylacetamide allosteric agonist and allosteric modulator of endogenous ligand function at human FFA2, by combining our previous knowledge of the orthosteric binding site with targeted examination of 4-CMTB structure-activity relationships and mutagenesis and chimeric receptor generation. Here we show that 4-CMTB is a selective agonist for FFA2 that binds to a site distinct from the orthosteric site of the receptor. Ligand structure-activity relationship studies indicated that the N-thiazolyl amide is likely to provide hydrogen bond donor/acceptor interactions with the receptor. Substitution at Leu173 or the exchange of the entire extracellular loop 2 of FFA2 with that of FFA3 was sufficient to reduce or ablate, respectively, allosteric communication between the endogenous and allosteric agonists. Thus, we conclude that extracellular loop 2 of human FFA2 is required for transduction of cooperative signaling between the orthosteric and an as-yet-undefined allosteric binding site of the FFA2 receptor that is occupied by 4-CMTB. PMID:21498659

  3. The key residue within the second extracellular loop of human EP3 involved in selectively turning down PGE2- and retaining PGE1-mediated signaling in live cells.

    Science.gov (United States)

    Akasaka, Hironari; Thaliachery, Natasha; Zheng, Xianghai; Blumenthal, Marissa; Nikhar, Sameer; Murdoch, Emma E; Ling, Qinglan; Ruan, Ke-He

    2017-02-15

    Key residues and binding mechanisms of PGE1 and PGE2 on prostanoid receptors are poorly understood due to the lack of X-ray structures for the receptors. We constructed a human EP3 (hEP3) model through integrative homology modeling using the X-ray structure of the β2-adrenergic receptor transmembrane domain and NMR structures of the thromboxane A2 receptor extracellular loops. PGE1 and PGE2 docking into the hEP3 model showed differing configurations within the extracellular ligand recognition site. While PGE2 could form possible binding contact with S211, PGE1 is unable to form similar contacts. Therefore, S211 could be the critical residue for PGE2 recognition, but is not a significant for PGE1. This prediction was confirmed using HEK293 cells transfected with hEP3 S211L cDNA. The S211L cells lost PGE2 binding and signaling. Interestingly, the S211L cells retained PGE1-mediated signaling. It indicates that S211 within the second extracellular loop is a key residue involved in turning down PGE2 signaling. Our study provided information that S211L within EP3 is the key residue to distinguish PGE1 and PGE2 binding to mediate diverse biological functions at the initial recognition step. The S211L mutant could be used as a model for studying the binding mechanism and signaling pathway specifically mediated by PGE1. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Novel insights into CB1 cannabinoid receptor signaling: a key interaction identified between the extracellular-3 loop and transmembrane helix 2.

    Science.gov (United States)

    Marcu, Jahan; Shore, Derek M; Kapur, Ankur; Trznadel, Megan; Makriyannis, Alexandros; Reggio, Patricia H; Abood, Mary E

    2013-05-01

    Activation of the cannabinoid CB1 receptor (CB1) is modulated by aspartate residue D2.63(176) in transmembrane helix (TMH) 2. Interestingly, D2.63 does not affect the affinity for ligand binding at the CB1 receptor. Studies in class A G protein-coupled receptors have suggested an ionic interaction between residues of TMH2 and 7. In this report, modeling studies identified residue K373 in the extracellular-3 (EC-3) loop in charged interactions with D2.63. We investigated this possibility by performing reciprocal mutations and biochemical studies. D2.63(176)A, K373A, D2.63(176)A-K373A, and the reciprocal mutant with the interacting residues juxtaposed D2.63(176)K-K373D were characterized using radioligand binding and guanosine 5'-3-O-(thio)triphosphate functional assays. None of the mutations resulted in a significant change in the binding affinity of N-(piperidiny-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichloro-phenyl)-4-methyl-1H-pyrazole-3-carboxamide hydrochloride (SR141716A) or (-)-3cis -[2-hydroxyl-4-(1,1-dimethyl-heptyl)phenyl]-trans-4-[3-hydroxyl-propyl] cyclohexan-1-ol (CP55,940). Modeling studies indicated that binding-site interactions and energies of interaction for CP55,940 were similar between wild-type and mutant receptors. However, the signaling of CP55,940, and (R)-(+)-[2,3-dihydro-5-methyl-3-[(4-morpholinyl)methyl]-pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl](1-naphthalenyl)-methanone mesylate (WIN55,212-2) was impaired at the D2.63(176)A-K373A and the single-alanine mutants. In contrast, the reciprocal D2.63(176)K-K373D mutant regained function for both CP55,940 and WIN55,212-2. Computational results indicate that the D2.63(176)-K373 ionic interaction strongly influences the conformation(s) of the EC-3 loop, providing a structure-based rationale for the importance of the EC-3 loop to signal transduction in CB1. The putative ionic interaction results in the EC-3 loop pulling over the top (extracellular side) of the receptor; this EC-3 loop conformation may serve

  5. Role of Conserved Disulfide Bridges and Aromatic Residues in Extracellular Loop 2 of Chemokine Receptor CCR8 for Chemokine and Small Molecule Binding

    DEFF Research Database (Denmark)

    Barington, Line; Rummel, Pia C; Lückmann, Michael

    2016-01-01

    and aromatic residues in extracellular loop 2 (ECL2) for ligand binding and activation in the chemokine receptor CCR8. We used IP3 accumulation and radioligand binding experiments to determine the impact of receptor mutagenesis on both chemokine and small molecule agonist and antagonist binding and action...... in CCR8. We find that the 7 transmembrane (7TM) receptor conserved disulfide bridge (7TM bridge) linking transmembrane helix (TM)III and ECL2 is crucial for chemokine and small molecule action, whereas the chemokine receptor conserved disulfide bridge between the N terminus and TMVII is needed only...... for chemokines. Furthermore, we find that two distinct aromatic residues in ECL2, Y184 (Cys+1) and Y187 (Cys+4), are crucial for binding of the CC chemokines CCL1 (agonist) and MC148 (antagonist), respectively, but not for small molecule binding. Finally, using in silico modeling, we predict an aromatic cluster...

  6. Second extracellular loop of human glucagon-like peptide-1 receptor (GLP-1R) has a critical role in GLP-1 peptide binding and receptor activation.

    Science.gov (United States)

    Koole, Cassandra; Wootten, Denise; Simms, John; Miller, Laurence J; Christopoulos, Arthur; Sexton, Patrick M

    2012-02-03

    The glucagon-like peptide-1 receptor (GLP-1R) is a therapeutically important family B G protein-coupled receptor (GPCR) that is pleiotropically coupled to multiple signaling effectors and, with actions including regulation of insulin biosynthesis and secretion, is one of the key targets in the management of type II diabetes mellitus. However, there is limited understanding of the role of the receptor core in orthosteric ligand binding and biological activity. To assess involvement of the extracellular loop (ECL) 2 in ligand-receptor interactions and receptor activation, we performed alanine scanning mutagenesis of loop residues and assessed the impact on receptor expression and GLP-1(1-36)-NH(2) or GLP-1(7-36)-NH(2) binding and activation of three physiologically relevant signaling pathways as follows: cAMP formation, intracellular Ca(2+) (Ca(2+)(i)) mobilization, and phosphorylation of extracellular signal-regulated kinases 1 and 2 (pERK1/2). Although antagonist peptide binding was unaltered, almost all mutations affected GLP-1 peptide agonist binding and/or coupling efficacy, indicating an important role in receptor activation. However, mutation of several residues displayed distinct pathway responses with respect to wild type receptor, including Arg-299 and Tyr-305, where mutation significantly enhanced both GLP-1(1-36)-NH(2)- and GLP-1(7-36)-NH(2)-mediated signaling bias for pERK1/2. In addition, mutation of Cys-296, Trp-297, Asn-300, Asn-302, and Leu-307 significantly increased GLP-1(7-36)-NH(2)-mediated signaling bias toward pERK1/2. Of all mutants studied, only mutation of Trp-306 to alanine abolished all biological activity. These data suggest a critical role of ECL2 of the GLP-1R in the activation transition(s) of the receptor and the importance of this region in the determination of both GLP-1 peptide- and pathway-specific effects.

  7. Modulation of constitutive activity and signaling bias of the ghrelin receptor by conformational constraint in the second extracellular loop

    DEFF Research Database (Denmark)

    Mokrosinski, Jacek; Frimurer, Thomas M; Sivertsen, Bjoern

    2012-01-01

    phenotypes as the negatively charged Glu residue. Computational chemistry analysis indicated that the propensity for the C-terminal segment of ECL2b to form an extended a-helix was increased from 15% in the wild type to 89% and 82% by introduction in position 204(C+6) of a Glu or a Lys residue, respectively....... Moreover, the constitutive activity of the receptor was inhibited by Zn(2+) binding in an engineered metal-ion site stabilizing an a-helical conformation of this loop segment. It is concluded that the high constitutive activity of the ghrelin receptor is dependent upon flexibility in the C-terminal segment...

  8. DNA immunization combined with scFv phage display identifies antagonistic GCGR specific antibodies and reveals new epitopes on the small extracellular loops.

    Science.gov (United States)

    van der Woning, Bas; De Boeck, Gitte; Blanchetot, Christophe; Bobkov, Vladimir; Klarenbeek, Alex; Saunders, Michael; Waelbroeck, Magali; Laeremans, Toon; Steyaert, Jan; Hultberg, Anna; De Haard, Hans

    2016-01-01

    The identification of functional monoclonal antibodies directed against G-protein coupled receptors (GPCRs) is challenging because of the membrane-embedded topology of these molecules. Here, we report the successful combination of llama DNA immunization with scFv-phage display and selections using virus-like particles (VLP) and the recombinant extracellular domain of the GPCR glucagon receptor (GCGR), resulting in glucagon receptor-specific antagonistic antibodies. By immunizing outbred llamas with plasmid DNA containing the human GCGR gene, we sought to provoke their immune system, which generated a high IgG1 response. Phage selections on VLPs allowed the identification of mAbs against the extracellular loop regions (ECL) of GCGR, in addition to multiple VH families interacting with the extracellular domain (ECD) of GCGR. Identifying mAbs binding to the ECL regions of GCGR is challenging because the large ECD covers the small ECLs in the energetically most favorable 'closed conformation' of GCGR. Comparison of Fab with scFv-phage display demonstrated that the multivalent nature of scFv display is essential for the identification of GCGR specific clones by selections on VLPs because of avid interaction. Ten different VH families that bound 5 different epitopes on the ECD of GCGR were derived from only 2 DNA-immunized llamas. Seven VH families demonstrated interference with glucagon-mediated cAMP increase. This combination of technologies proved applicable in identifying multiple functional binders in the class B GPCR context, suggesting it is a robust approach for tackling difficult membrane proteins.

  9. Short Communication: HIV-1 Variants That Use Mouse CCR5 Reveal Critical Interactions of gp120's V3 Crown with CCR5 Extracellular Loop 1.

    Science.gov (United States)

    Platt, Emily J; Durnin, James P; Kabat, David

    2015-10-01

    The CCR5 coreceptor amino terminus and extracellular (ECL) loops 1 and 2 have been implicated in HIV-1 infections, with species differences in these regions inhibiting zoonoses. Interactions of gp120 with CD4 and CCR5 reduce constraints on metastable envelope subunit gp41, enabling gp41 conformational changes needed for infection. We previously selected HIV-1JRCSF variants that efficiently use CCR5(Δ18) with a deleted amino terminus or CCR5(HHMH) with ECL2 from an NIH/Swiss mouse. Unexpectedly, the adaptive gp120 mutations were nearly identical, suggesting that they function by weakening gp120's grip on gp41 and/or by increasing interactions with ECL1. To analyze this and further wean HIV-1 from human CCR5, we selected variants using CCR5(HMMH) with murine ECL1 and 2 sequences. HIV-1JRCSF mutations adaptive for CCR5(Δ18) and CCR5(HHMH) were generally maladaptive for CCR5(HMMH), whereas the converse was true for CCR5(HMMH) adaptations. The HIV-1JRCSF variant adapted to CCR5(HMMH) also weakly used intact NIH/Swiss mouse CCR5. Our results strongly suggest that HIV-1JRCSF makes functionally critical contacts with human ECL1 and that adaptation to murine ECL1 requires multiple mutations in the crown of gp120's V3 loop.

  10. Highly conserved glutamic acid in the extracellular IV–V loop in rhodopsins acts as the counterion in retinochrome, a member of the rhodopsin family

    Science.gov (United States)

    Terakita, Akihisa; Yamashita, Takahiro; Shichida, Yoshinori

    2000-01-01

    Retinochrome is a member of the rhodopsin family having a chromophore retinal and functioning as a retinal photoisomerase in squid photoreceptor cells. Unlike vertebrate rhodopsins, but like many invertebrate rhodopsins, retinochrome does not have a glutamic acid at position 113 to serve as a counterion for the protonated retinylidene Schiff base. Here we investigated possible counterions in retinochrome by site-specific mutagenesis. Our results showed that the counterion is the glutamic acid at position 181, at which almost all the pigments in the rhodopsin family, including vertebrate and invertebrate rhodopsins, have a glutamic or aspartic acid. The remarkable exceptions are the long-wavelength visual pigments that have a histidine that, together with a nearby lysine, serves as a chloride-binding site. Replacement of Glu-181 of bovine rhodopsin with Gln caused a 10-nm red-shift of absorption maximum. Because the position at 181 is in the extracellular loop connecting the transmembrane helices VI and V, these results demonstrate the importance of this loop to function for spectral tuning in the rhodopsin family. PMID:11106382

  11. Asparagine, valine, and threonine in the third extracellular loop of muscarinic receptor have essential roles in the positive cooperativity of strychnine-like allosteric modulators.

    Science.gov (United States)

    Jakubík, J; Krejcí, A; Dolezal, V

    2005-05-01

    We have investigated allosteric interactions of four closely related strychnine-like substances: Wieland-Gumlich aldehyde (WGA), propargyl Wieland-Gumlich aldehyde, strychnine, and brucine with N-methylscopolamine (NMS) on M(3) subtype of muscarinic receptor genetically modified in the second or the third extracellular loop to corresponding loops of M(2) subtype (M(3)o2 and M(3)o3 chimera). The M(3)o2 chimeric receptor The exhibited no change in either affinity of strychnine, brucine, and WGA or in cooperativity of brucine or WGA, whereas both parameters for propargyl-WGA changed. In contrast, there was a change in affinity of all tested modulators (except for brucine) and in their cooperativity in the M(3)o3 chimera. Directions of affinity changes in both chimeras were always toward values of the donor M(2) subtype, but changes in cooperativity were variable. Compared with the native M(3) receptor, strychnine displayed a slight increase in positive cooperativity and propargyl-WGA a robust decrease in negative cooperativity at M(3)o2 chimera. Similar changes were found in the M(3)o3 chimera. Interestingly, cooperativity of brucine and WGA at the M(3)o3 chimera changed from negative to positive. This is the first evidence of constitution of positive cooperativity of WGA by switching sequences of two parental receptors, both exhibiting negative cooperativity. Gradual replacement of individual amino acids revealed that only three residues (NVT of the o3 loop of the M(2) receptor) are involved in this effect. Data suggest that these amino acids are essential for propagation of a conformation change resulting in positive cooperativity induced by these modulators.

  12. An improved and robust DNA immunization method to develop antibodies against extracellular loops of multi-transmembrane proteins.

    Science.gov (United States)

    Hazen, Meredith; Bhakta, Sunil; Vij, Rajesh; Randle, Steven; Kallop, Dara; Chiang, Vicki; Hötzel, Isidro; Jaiswal, Bijay S; Ervin, Karen E; Li, Bing; Weimer, Robby M; Polakis, Paul; Scheller, Richard H; Junutula, Jagath R; Hongo, Jo-Anne S

    2014-01-01

    Multi-transmembrane proteins are especially difficult targets for antibody generation largely due to the challenge of producing a protein that maintains its native conformation in the absence of a stabilizing membrane. Here, we describe an immunization strategy that successfully resulted in the identification of monoclonal antibodies that bind specifically to extracellular epitopes of a 12 transmembrane protein, multi-drug resistant protein 4 (MRP4). These monoclonal antibodies were developed following hydrodynamic tail vein immunization with a cytomegalovirus (CMV) promoter-based plasmid expressing MRP4 cDNA and were characterized by flow cytometry. As expected, the use of the immune modulators fetal liver tyrosine kinase 3 ligand (Flt3L) and granulocyte-macrophage colony-stimulating factor positively enhanced the immune response against MRP4. Imaging studies using CMV-based plasmids expressing luciferase showed that the in vivo half-life of the target antigen was less than 48 h using CMV-based plasmids, thus necessitating frequent boosting with DNA to achieve an adequate immune response. We also describe a comparison of plasmids, which contained MRP4 cDNA with either the CMV or CAG promoters, used for immunizations. The observed luciferase activity in this comparison demonstrated that the CAG promoter-containing plasmid pCAGGS induced prolonged constitutive expression of MRP4 and an increased anti-MRP4 specific immune response even when the plasmid was injected less frequently. The method described here is one that can be broadly applicable as a general immunization strategy to develop antibodies against multi-transmembrane proteins, as well as target antigens that are difficult to express or purify in native and functionally active conformation.

  13. Existence of Néel Order in the S=1 Bilinear-Biquadratic Heisenberg Model via Random Loops

    Science.gov (United States)

    Lees, Benjamin

    2016-10-01

    We consider the general spin-1 SU(2) invariant Heisenberg model with a two-body interaction. A random loop model is introduced and relation to quantum spin systems is proved. Using this relation it is shown that for dimensions 3 and above Néel order occurs for a large range of values of the relative strength of the bilinear (- J 1) and biquadratic (- J 2) interaction terms. The proof uses the method of reflection positivity and infrared bounds. Links between spin correlations and loop correlations are proved.

  14. Peptides from second extracellular loop of C-C chemokine receptor type 5 (CCR5) inhibit diverse strains of HIV-1.

    Science.gov (United States)

    Dogo-Isonagie, Cajetan; Lam, Son; Gustchina, Elena; Acharya, Priyamvada; Yang, Yongping; Shahzad-ul-Hussan, Syed; Clore, G Marius; Kwong, Peter D; Bewley, Carole A

    2012-04-27

    To initiate HIV entry, the HIV envelope protein gp120 must engage its primary receptor CD4 and a coreceptor CCR5 or CXCR4. In the absence of a high resolution structure of a gp120-coreceptor complex, biochemical studies of CCR5 have revealed the importance of its N terminus and second extracellular loop (ECL2) in binding gp120 and mediating viral entry. Using a panel of synthetic CCR5 ECL2-derived peptides, we show that the C-terminal portion of ECL2 (2C, comprising amino acids Cys-178 to Lys-191) inhibit HIV-1 entry of both CCR5- and CXCR4-using isolates at low micromolar concentrations. In functional viral assays, these peptides inhibited HIV-1 entry in a CD4-independent manner. Neutralization assays designed to measure the effects of CCR5 ECL2 peptides when combined with either with the small molecule CD4 mimetic NBD-556, soluble CD4, or the CCR5 N terminus showed additive inhibition for each, indicating that ECL2 binds gp120 at a site distinct from that of N terminus and acts independently of CD4. Using saturation transfer difference NMR, we determined the region of CCR5 ECL2 used for binding gp120, showed that it can bind to gp120 from both R5 and X4 isolates, and demonstrated that the peptide interacts with a CD4-gp120 complex in a similar manner as to gp120 alone. As the CCR5 N terminus-gp120 interactions are dependent on CD4 activation, our data suggest that gp120 has separate binding sites for the CCR5 N terminus and ECL2, the ECL2 binding site is present prior to CD4 engagement, and it is conserved across CCR5- and CXCR4-using strains. These peptides may serve as a starting point for the design of inhibitors with broad spectrum anti-HIV activity.

  15. A cluster of aspartic residues in the extracellular loop II of PAR 4 is important for thrombin interaction and activation of platelets.

    Science.gov (United States)

    Sánchez Centellas, Daniel; Gudlur, Sushanth; Vicente-Carrillo, Alejandro; Ramström, Sofia; Lindahl, Tomas L

    2017-06-01

    Thrombin activates platelets via proteolytic cleavage of protease-activated receptors (PARs) 1 and 4. The two PARs have distinct but complementary roles. The mechanisms responsible for PAR1 activation by thrombin have been extensively studied. However, much less is known regarding thrombin activation of PAR4, especially the potential involvement of regions of PAR4 other than the N-terminal, which is bound to the catalytic site of thrombin. We have studied PAR4 in S. cerevisiae strain MMY12, an expression system in which the GPCR receptors are connected to a Lac Z reporter gene resulting in increased β-galactosidase activity. This approach was used to assess PAR4 mutants to evaluate the contribution of different aspartic residues in facilitating PAR4 activation. Furthermore, peptides mimicking parts of the PAR4 N-terminal and the second extracellular loop (ECLII) were tested for their ability to inhibit platelet activation by thrombin. Binding of these peptides to γ-thrombin was studied by monitoring the decrease in tryptophan fluorescence intensity of thrombin. We conclude that not only the N-terminal but also the electronegative aspartic residues D224, D230 and D235 (located in ECLII) are be important for PAR4 binding to thrombin. We further suggest that they play a role for the tethered ligand binding to the receptor, as mutations also affected activation in response to a PAR4-activating peptide mimicking the new N-terminal formed after cleavage. This agrees with previous results on PAR1 and thrombin binding. We suggest that the ECLII of PAR4 could be a potential target for antithrombotic drug development. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. The extracellular loop 2 (ECL2 of the human histamine H4 receptor substantially contributes to ligand binding and constitutive activity.

    Directory of Open Access Journals (Sweden)

    David Wifling

    Full Text Available In contrast to the corresponding mouse and rat orthologs, the human histamine H4 receptor (hH4R shows extraordinarily high constitutive activity. In the extracellular loop (ECL, replacement of F169 by V as in the mouse H4R significantly reduced constitutive activity. Stabilization of the inactive state was even more pronounced for a double mutant, in which, in addition to F169V, S179 in the ligand binding site was replaced by M. To study the role of the FF motif in ECL2, we generated the hH4R-F168A mutant. The receptor was co-expressed in Sf9 insect cells with the G-protein subunits Gαi2 and Gβ1γ2, and the membranes were studied in [3H]histamine binding and functional [35S]GTPγS assays. The potency of various ligands at the hH4R-F168A mutant decreased compared to the wild-type hH4R, for example by 30- and more than 100-fold in case of the H4R agonist UR-PI376 and histamine, respectively. The high constitutive activity of the hH4R was completely lost in the hH4R-F168A mutant, as reflected by neutral antagonism of thioperamide, a full inverse agonist at the wild-type hH4R. By analogy, JNJ7777120 was a partial inverse agonist at the hH4R, but a partial agonist at the hH4R-F168A mutant, again demonstrating the decrease in constitutive activity due to F168A mutation. Thus, F168 was proven to play a key role not only in ligand binding and potency, but also in the high constitutive activity of the hH4R.

  17. The extracellular loop 2 (ECL2) of the human histamine H4 receptor substantially contributes to ligand binding and constitutive activity.

    Science.gov (United States)

    Wifling, David; Bernhardt, Günther; Dove, Stefan; Buschauer, Armin

    2015-01-01

    In contrast to the corresponding mouse and rat orthologs, the human histamine H4 receptor (hH4R) shows extraordinarily high constitutive activity. In the extracellular loop (ECL), replacement of F169 by V as in the mouse H4R significantly reduced constitutive activity. Stabilization of the inactive state was even more pronounced for a double mutant, in which, in addition to F169V, S179 in the ligand binding site was replaced by M. To study the role of the FF motif in ECL2, we generated the hH4R-F168A mutant. The receptor was co-expressed in Sf9 insect cells with the G-protein subunits Gαi2 and Gβ1γ2, and the membranes were studied in [3H]histamine binding and functional [35S]GTPγS assays. The potency of various ligands at the hH4R-F168A mutant decreased compared to the wild-type hH4R, for example by 30- and more than 100-fold in case of the H4R agonist UR-PI376 and histamine, respectively. The high constitutive activity of the hH4R was completely lost in the hH4R-F168A mutant, as reflected by neutral antagonism of thioperamide, a full inverse agonist at the wild-type hH4R. By analogy, JNJ7777120 was a partial inverse agonist at the hH4R, but a partial agonist at the hH4R-F168A mutant, again demonstrating the decrease in constitutive activity due to F168A mutation. Thus, F168 was proven to play a key role not only in ligand binding and potency, but also in the high constitutive activity of the hH4R.

  18. Fiber into the loop transmission. Transmision por fibra optica hacia el abonado

    Energy Technology Data Exchange (ETDEWEB)

    Martin Minguez, A.

    1993-03-15

    In this paper some considerations are presented about Fiber into the Loop (FITL) transmission. A preliminary comparison between copper and optical cables is made and the conclusion is the convenience to introduce optical fiber in the subcriber loop for narrow-band and broadband services transmission. Some comments are made about the structure of the optical plant regarding topology: passive, active, point to point, point to multipoint, etc., and also, about the use of the optical windows (2nd and 3nd) in the fiber. Procedures for the optical maintenance of the network are outlined due to their great importance to the PTTs. Transmission methods and their application in the PON (Passive Optical Networks) for point to multipoint transmission (TDM, TDMA) are considered. (Author)

  19. Expression of Human Vascular Endothelial Growth Factor Receptor Flt-1 Extracellular Domain 1-3 Loop cDNA in Pichia pastoris, Purification of the Expressed Product and Detection of Its Biological Activity

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective To express human vascular endothelial growth factor receptor Flt-1 extracellular domain 1-3 loop cDNA in Pichia. Pastroris, and to purify the expressed product and detect its biological activity. Methods By inserting human Flt-1 (1-3 loop) cDNA coding 316 amino acid residues into Pichia pastoris expression vector pPIC9K containing AOX1 promoter and the sequences of α secreting signal peptides, a recombinant expression plasmid pPIC9K/Flt-1 (1-3) was constructed and transformed to yeast host strain GS115, then His+ Muts phenotype transformant was screened out and cultured in flasks, and Flt-1 (1-3) was expressed under the induction of 1% methanol. Results SDS-PAGE showed that after being induced with 1% methanol for 4d, the expressed product existed in supernatant in the form of soluble molecule and contained 60% of total protein expressed. Western blot showed good antigenicity and specificity of expressed product. After being purified by CM-Sepharose FF and Sephacryl S-100 chromatography, the purity of the expressed product reached above 90%. Biological assay proved that the expressed product could bind to hVEGF165 and inhibit the proliferation of HUVEC stimulated by hVEGF165. Conclusion Human vascular endothelial growth factor receptor Flt-1 extracellular domain 1-3 loop was successfully expressed. The study lays a foundation for further application of the expressed product in the treatment of vasoformation related diseases, such as tumor and diabetic retinopathy.

  20. Single amino acid insertions in extracellular loop 2 of Bombyx mori ABCC2 disrupt its receptor function for Bacillus thuringiensis Cry1Ab and Cry1Ac but not Cry1Aa toxins.

    Science.gov (United States)

    Tanaka, Shiho; Miyamoto, Kazuhisa; Noda, Hiroaki; Endo, Haruka; Kikuta, Shingo; Sato, Ryoichi

    2016-04-01

    In a previous report, seven Cry1Ab-resistant strains were identified in the silkworm, Bombyx mori; these strains were shown to have a tyrosine insertion at position 234 in extracellular loop 2 of the ABC transporter C2 (BmABCC2). This insertion was confirmed to destroy the receptor function of BmABCC2 and confer the strains resistance against Cry1Ab and Cry1Ac. However, these strains were susceptible to Cry1Aa. In this report, we examined the mechanisms of the loss of receptor function of the transporter by expressing mutations in Sf9 cells. After replacement of one or two of the five amino acid residues in loop 2 of the susceptible BmABCC2 gene [BmABCC2_S] with alanine, cells still showed susceptibility, retaining the receptor function. Five mutants with single amino acid insertions at position 234 in BmABCC2 were also generated, resulting in loop 2 having six amino acids, which corresponds to replacing the tyrosine insertion in the resistant BmABCC2 gene [BmABCC2_R(+(234)Y)] with another amino acid. All five mutants exhibited loss of function against Cry1Ab and Cry1Ac. These results suggest that the amino acid sequence in loop 2 is less important than the loop size (five vs. six amino acids) or loop structure for Cry1Ab and Cry1Ac activity. Several domain-swapped mutant toxins were then generated among Cry1Aa, Cry1Ab, and Cry1Ac, which are composed of three domains. Swapped mutants containing domain II of Cry1Ab or Cry1Ac did not kill Sf9 cells expressing BmABCC2_R(+(234)Y), suggesting that domain II of the Cry toxin is related to the interaction with the receptor function of BmABCC2. This also suggests that different reactions against Bt-toxins in some B. mori strains, that is, Cry1Ab resistance or Cry1Aa susceptibility, are attributable to structural differences in domain II of Cry1A toxins.

  1. Activation of phagocytic cells by Staphylococcus epidermidis biofilms: effects of extracellular matrix proteins and the bacterial stress protein GroEL on netosis and MRP-14 release.

    Science.gov (United States)

    Dapunt, Ulrike; Gaida, Matthias M; Meyle, Eva; Prior, Birgit; Hänsch, Gertrud M

    2016-07-01

    The recognition and phagocytosis of free-swimming (planktonic) bacteria by polymorphonuclear neutrophils have been investigated in depth. However, less is known about the neutrophil response towards bacterial biofilms. Our previous work demonstrated that neutrophils recognize activating entities within the extracellular polymeric substance (EPS) of biofilms (the bacterial heat shock protein GroEL) and that this process does not require opsonization. Aim of this study was to evaluate the release of DNA by neutrophils in response to biofilms, as well as the release of the inflammatory cytokine MRP-14. Neutrophils were stimulated with Staphylococcus epidermidis biofilms, planktonic bacteria, extracted EPS and GroEL. Release of DNA and of MRP-14 was evaluated. Furthermore, tissue samples from patients suffering from biofilm infections were collected and evaluated by histology. MRP-14 concentration in blood samples was measured. We were able to show that biofilms, the EPS and GroEL induce DNA release. MRP-14 was only released after stimulation with EPS, not GroEL. Histology of tissue samples revealed MRP-14 positive cells in association with neutrophil infiltration and MRP-14 concentration was elevated in blood samples of patients suffering from biofilm infections. Our data demonstrate that neutrophil-activating entities are present in the EPS and that GroEL induces DNA release by neutrophils.

  2. A maraviroc-resistant HIV-1 with narrow cross-resistance to other CCR5 antagonists depends on both N-terminal and extracellular loop domains of drug-bound CCR5.

    Science.gov (United States)

    Tilton, John C; Wilen, Craig B; Didigu, Chukwuka A; Sinha, Rohini; Harrison, Jessamina E; Agrawal-Gamse, Caroline; Henning, Elizabeth A; Bushman, Frederick D; Martin, Jeffrey N; Deeks, Steven G; Doms, Robert W

    2010-10-01

    CCR5 antagonists inhibit HIV entry by binding to a coreceptor and inducing changes in the extracellular loops (ECLs) of CCR5. In this study, we analyzed viruses from 11 treatment-experienced patients who experienced virologic failure on treatment regimens containing the CCR5 antagonist maraviroc (MVC). Viruses from one patient developed high-level resistance to MVC during the course of treatment. Although resistance to one CCR5 antagonist is often associated with broad cross-resistance to other agents, these viruses remained sensitive to most other CCR5 antagonists, including vicriviroc and aplaviroc. MVC resistance was dependent upon mutations within the V3 loop of the viral envelope (Env) protein and was modulated by additional mutations in the V4 loop. Deep sequencing of pretreatment plasma viral RNA indicated that resistance appears to have occurred by evolution of drug-bound CCR5 use, despite the presence of viral sequences predictive of CXCR4 use. Envs obtained from this patient before and during MVC treatment were able to infect cells expressing very low CCR5 levels, indicating highly efficient use of a coreceptor. In contrast to previous reports in which CCR5 antagonist-resistant viruses interact predominantly with the N terminus of CCR5, these MVC-resistant Envs were also dependent upon the drug-modified ECLs of CCR5 for entry. Our results suggest a model of CCR5 cross-resistance whereby viruses that predominantly utilize the N terminus are broadly cross-resistant to multiple CCR5 antagonists, whereas viruses that require both the N terminus and antagonist-specific ECL changes demonstrate a narrow cross-resistance profile.

  3. Effects of long-term active immunization with the second extracellular loop of human β1- or β3-adrenoceptors in thoracic aorta and mesenteric arteries in Lewis rats.

    Science.gov (United States)

    Montaudon, E; Dubreil, L; Lalanne, V; Jagu, B; Toumaniantz, G; Thorin, C; Henrion, D; Desfontis, J-C; Martignat, L; Mallem, M Y

    2016-12-01

    To evaluate whether active immunization producing β1- or β3-antibodies (β1-ABs and β3-ABs) detected in sera of patients with dilated cardiomyopathies has deleterious effects on vascular reactivity in Lewis rat thoracic aorta (TA) and small mesenteric arteries (SMA). Lewis rats were immunized for 6months with peptidic sequences corresponding to the second extracellular loop of β1- and β3-adrenoceptors (ARs). During the immunization, systolic blood pressure (SBP) was monitored using the tail cuff method. The vascular reactivity of immunized rats was assessed by ex vivo studies on SMA and TA using various β-AR agonists, phenylephrine and KCl. The immunizations producing functional β1-ABs and β3-ABs did not affect the SBP. However, in TA from β1-AR-immunized rats, the relaxations mediated by dobutamine and salbutamol were significantly impaired in comparison with adjuvant rats whereas nebivolol-induced relaxation was not modified. Moreover, phenylephrine and KCl-mediated contractions were enhanced in these rats. In contrast, immunization with β3-AR peptide led to the increase of relaxations induced by dobutamine in TA but did not change those induced by salbutamol and nebivolol. Surprisingly, in SMA from both rats immunized with β1- or β3-peptides, relaxations induced by the various β-agonists were not changed whereas phenylephrine and KCl-mediated contractions were impaired. Our study shows that β1- and β3-ABs can affect vascular reactivity. β1-ABs would have a pathogenic action whereas β3-ABs would have a beneficial effect on aorta reactivity. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. The second extracellular loop of pore-forming subunits of ATP-binding cassette transporters for basic amino acids plays a crucial role in interaction with the cognate solute binding protein(s).

    Science.gov (United States)

    Eckey, Viola; Weidlich, Daniela; Landmesser, Heidi; Bergmann, Ulf; Schneider, Erwin

    2010-04-01

    In the thermophile Geobacillus stearothermophilus, the uptake of basic amino acids is mediated by an ABC transporter composed of the substrate binding protein (receptor) ArtJ and a homodimer each of the pore-forming subunit, ArtM, and the nucleotide-binding subunit, ArtP. We recently identified two putative binding sites in ArtJ that might interact with the Art(MP)(2) complex, thereby initiating the transport cycle (A. Vahedi-Faridi et al., J. Mol. Biol. 375:448-459, 2008). Here we investigated the contribution of charged amino acid residues in the second extracellular loop of ArtM to contact with ArtJ. Our results demonstrate a crucial role for residues K177, R185, and E188, since mutations to oppositely charged amino acids or glutamine led to a complete loss of ArtJ-stimulated ATPase activity of the complex variants in proteoliposomes. The defects could not be suppressed by ArtJ variants carrying mutations in site I (K39E and K152E) or II (E163K and D170K), suggesting a more complex interplay than that by a single salt bridge. These findings were supported by cross-linking assays demonstrating physical proximity between ArtJ(N166C) and ArtM(E182C). The importance of positively charged residues for receptor-transporter interaction was underscored by mutational analysis of the closely related transporter HisJ/LAO-HisQMP(2) of Salmonella enterica serovar Typhimurium. While transporter variants with mutated positively charged residues in HisQ displayed residual ATPase activities, corresponding mutants of HisM could no longer be stimulated by HisJ/LAO. Interestingly, the ATPase activity of the HisQM(K187E)P(2) variant was inhibited by l- and d-histidine in detergent, suggesting a role of the residue in preventing free histidine from gaining access to the substrate binding site within HisQM.

  5. The Second Extracellular Loop of Pore-Forming Subunits of ATP-Binding Cassette Transporters for Basic Amino Acids Plays a Crucial Role in Interaction with the Cognate Solute Binding Protein(s)▿

    Science.gov (United States)

    Eckey, Viola; Weidlich, Daniela; Landmesser, Heidi; Bergmann, Ulf; Schneider, Erwin

    2010-01-01

    In the thermophile Geobacillus stearothermophilus, the uptake of basic amino acids is mediated by an ABC transporter composed of the substrate binding protein (receptor) ArtJ and a homodimer each of the pore-forming subunit, ArtM, and the nucleotide-binding subunit, ArtP. We recently identified two putative binding sites in ArtJ that might interact with the Art(MP)2 complex, thereby initiating the transport cycle (A. Vahedi-Faridi et al., J. Mol. Biol. 375:448-459, 2008). Here we investigated the contribution of charged amino acid residues in the second extracellular loop of ArtM to contact with ArtJ. Our results demonstrate a crucial role for residues K177, R185, and E188, since mutations to oppositely charged amino acids or glutamine led to a complete loss of ArtJ-stimulated ATPase activity of the complex variants in proteoliposomes. The defects could not be suppressed by ArtJ variants carrying mutations in site I (K39E and K152E) or II (E163K and D170K), suggesting a more complex interplay than that by a single salt bridge. These findings were supported by cross-linking assays demonstrating physical proximity between ArtJ(N166C) and ArtM(E182C). The importance of positively charged residues for receptor-transporter interaction was underscored by mutational analysis of the closely related transporter HisJ/LAO-HisQMP2 of Salmonella enterica serovar Typhimurium. While transporter variants with mutated positively charged residues in HisQ displayed residual ATPase activities, corresponding mutants of HisM could no longer be stimulated by HisJ/LAO. Interestingly, the ATPase activity of the HisQM(K187E)P2 variant was inhibited by l- and d-histidine in detergent, suggesting a role of the residue in preventing free histidine from gaining access to the substrate binding site within HisQM. PMID:20154136

  6. Rapid, Sensitive Detection of Bartonella quintana by Loop-Mediated Isothermal Amplification of the groEL Gene

    Science.gov (United States)

    Hu, Shoukui; Niu, Lina; Luo, Lijuan; Song, Xiuping; Sun, Jimin; Liu, Qiyong

    2016-01-01

    Trench fever, caused by Bartonella quintana, is recognized as a re-emerging and neglected disease. Rapid and sensitive detection approaches are urgently required to monitor and help control B. quintana infections. Here, loop-mediated isothermal amplification (LAMP), which amplifies target DNA at a fixed temperature with high sensitivity, specificity and rapidity, was employed to detect B. quintana. Thirty-six strains, including 10 B. quintana, 13 other Bartonella spp., and 13 other common pathogens, were applied to verify and evaluate the LAMP assay. The specificity of the LAMP assay was 100%, and the limit of detection was 125 fg/reaction. The LAMP assay was compared with qPCR in the examination of 100 rhesus and 20 rhesus-feeder blood samples; the diagnostic accuracy was found to be 100% when LAMP was compared to qPCR, but the LAMP assay was significantly more sensitive (p < 0.05). Thus, LAMP methodology is a useful for diagnosis of trench fever in humans and primates, especially in low-resource settings, because of its rapid, sensitive detection that does not require sophisticated equipment. PMID:27916953

  7. Rapid, Sensitive Detection of Bartonella quintana by Loop-Mediated Isothermal Amplification of the groEL Gene

    Directory of Open Access Journals (Sweden)

    Shoukui Hu

    2016-12-01

    Full Text Available Trench fever, caused by Bartonella quintana, is recognized as a re-emerging and neglected disease. Rapid and sensitive detection approaches are urgently required to monitor and help control B. quintana infections. Here, loop-mediated isothermal amplification (LAMP, which amplifies target DNA at a fixed temperature with high sensitivity, specificity and rapidity, was employed to detect B. quintana. Thirty-six strains, including 10 B. quintana, 13 other Bartonella spp., and 13 other common pathogens, were applied to verify and evaluate the LAMP assay. The specificity of the LAMP assay was 100%, and the limit of detection was 125 fg/reaction. The LAMP assay was compared with qPCR in the examination of 100 rhesus and 20 rhesus-feeder blood samples; the diagnostic accuracy was found to be 100% when LAMP was compared to qPCR, but the LAMP assay was significantly more sensitive (p < 0.05. Thus, LAMP methodology is a useful for diagnosis of trench fever in humans and primates, especially in low-resource settings, because of its rapid, sensitive detection that does not require sophisticated equipment.

  8. Pregnancy Specific Glycoprotein 17 Binds to the Extracellular Loop 2 of its Receptor, CD9, and Induces the Secretion of IL-lO, IL-6, PGE2 and TGFbeta1 in Murine Macrophages

    Science.gov (United States)

    2004-07-09

    Military Medical History -Public Health -Tropical Medicine & Hygiene Graduate Education Office Dr. Cinda Helke, Associate Dean Janet Anastasi, Program...plasma membrane adhesion and fusion. J. Cell Biol. 137, 105–112. Zelus, B.D., Wessner, D.R., Williams , R.K., Pensiero, M.N., Phibbs, F.T., deSouza, M...suggest that in macrophages elevated intracellular cAMP results in extracellular signal-regulated kinase (ERK) activation [67]. In addition, Williams and

  9. Evaluation of the perturbation of the mesh Bra Breast TiLoop in the planning process-radiotherapy; Evaluacion de la perturbacion de la malla mamaria TiLoop Bra en el proceso de planificacion-tratamiento radioterapico

    Energy Technology Data Exchange (ETDEWEB)

    Camacho, C.; Pujades, M. C.; Perez-Calatayud, J.; Lliso, F.; Carmona, V.; Richart, J.; Ballester, F.

    2011-07-01

    The aim of this study is to determine the dosimetric impact TiLoop Mesh Bra breast radiotherapy treatments, and their influence on both the quality and the disruption of the gray levels of the radiographic image required for treatment planning.

  10. El

    NARCIS (Netherlands)

    de Beer, P.T.; Luttikhuizen, R.; Barbier, J.C.; Gautii, J.

    1998-01-01

    El objetivo de esta publicacisn es aportar una serie de novedosas contribuciones que abordan, desde diversos angulos, el candente problema del empleo. Su contenido se refiere a los principales pamses de la Comunidad Econsmica Europea y Estados Unidos, analizando las caractermsticas y causas del

  11. El

    NARCIS (Netherlands)

    de Beer, P.T.; Luttikhuizen, R.; Barbier, J.C.; Gautii, J.

    1998-01-01

    El objetivo de esta publicacisn es aportar una serie de novedosas contribuciones que abordan, desde diversos angulos, el candente problema del empleo. Su contenido se refiere a los principales pamses de la Comunidad Econsmica Europea y Estados Unidos, analizando las caractermsticas y causas del dese

  12. El

    NARCIS (Netherlands)

    de Beer, P.T.; Luttikhuizen, R.; Barbier, J.C.; Gautii, J.

    1998-01-01

    El objetivo de esta publicacisn es aportar una serie de novedosas contribuciones que abordan, desde diversos angulos, el candente problema del empleo. Su contenido se refiere a los principales pamses de la Comunidad Econsmica Europea y Estados Unidos, analizando las caractermsticas y causas del dese

  13. Loop-to-loop coupling.

    Energy Technology Data Exchange (ETDEWEB)

    Warne, Larry Kevin; Lucero, Larry Martin; Langston, William L.; Salazar, Robert Austin; Coleman, Phillip Dale; Basilio, Lorena I.; Bacon, Larry Donald

    2012-05-01

    This report estimates inductively-coupled energy to a low-impedance load in a loop-to-loop arrangement. Both analytical models and full-wave numerical simulations are used and the resulting fields, coupled powers and energies are compared. The energies are simply estimated from the coupled powers through approximations to the energy theorem. The transmitter loop is taken to be either a circular geometry or a rectangular-loop (stripline-type) geometry that was used in an experimental setup. Simple magnetic field models are constructed and used to estimate the mutual inductance to the receiving loop, which is taken to be circular with one or several turns. Circuit elements are estimated and used to determine the coupled current and power (an equivalent antenna picture is also given). These results are compared to an electromagnetic simulation of the transmitter geometry. Simple approximate relations are also given to estimate coupled energy from the power. The effect of additional loads in the form of attached leads, forming transmission lines, are considered. The results are summarized in a set of susceptibility-type curves. Finally, we also consider drives to the cables themselves and the resulting common-to-differential mode currents in the load.

  14. Insertion of tetracysteine motifs into dopamine transporter extracellular domains.

    Directory of Open Access Journals (Sweden)

    Deanna M Navaroli

    Full Text Available The neuronal dopamine transporter (DAT is a major determinant of extracellular dopamine (DA levels and is the primary target for a variety of addictive and therapeutic psychoactive drugs. DAT is acutely regulated by protein kinase C (PKC activation and amphetamine exposure, both of which modulate DAT surface expression by endocytic trafficking. In order to use live imaging approaches to study DAT endocytosis, methods are needed to exclusively label the DAT surface pool. The use of membrane impermeant, sulfonated biarsenic dyes holds potential as one such approach, and requires introduction of an extracellular tetracysteine motif (tetraCys; CCPGCC to facilitate dye binding. In the current study, we took advantage of intrinsic proline-glycine (Pro-Gly dipeptides encoded in predicted DAT extracellular domains to introduce tetraCys motifs into DAT extracellular loops 2, 3, and 4. [(3H]DA uptake studies, surface biotinylation and fluorescence microscopy in PC12 cells indicate that tetraCys insertion into the DAT second extracellular loop results in a functional transporter that maintains PKC-mediated downregulation. Introduction of tetraCys into extracellular loops 3 and 4 yielded DATs with severely compromised function that failed to mature and traffic to the cell surface. This is the first demonstration of successful introduction of a tetracysteine motif into a DAT extracellular domain, and may hold promise for use of biarsenic dyes in live DAT imaging studies.

  15. Matrix Extracellular Phosphoglycoprotein Inhibits Phosphate Transport

    OpenAIRE

    Marks, J; Churchill, L J; Debnam, E. S.; Unwin, R J

    2008-01-01

    The role of putative humoral factors, known as phosphatonins, in phosphate homeostasis and the relationship between phosphate handling by the kidney and gastrointestinal tract are incompletely understood. Matrix extracellular phosphoglycoprotein (MEPE), one of several candidate phosphatonins, promotes phosphaturia, but whether it also affects intestinal phosphate absorption is unknown. Here, using the in situ intestinal loop technique, we demonstrated that short-term infusion of MEPE inhibits...

  16. Research on high-burn fuel: the Cabri water loop reactor project; La investigacion sobre combustible de alto quemado: El proyecto del reactor Cabri con lazo de agua

    Energy Technology Data Exchange (ETDEWEB)

    Conde Lopez, J. M.; Recio Santamaria, M. [Consejo de Seguridad Nuclear. Madrid (Spain)

    2000-07-01

    This paper describes the present status of the nuclear fuel utilization both in the national and international arenas. Details on the fuel-related research programs actually ongoing are given. The interests and strategic lines stablished by the CSN regarding high burnup fuel research are described. Specifically, an analysis is made of the reasons underlying the CSN's decision to participate in the IPSN's CABRI Water Loop high burnup fuel research program. The core of the paper is devoted to the description of the CABRI project contents and of the technical aspects in the behaviour of high burnup fuel that will be studied through the foreseen integral and separate effects tests. Finally, a summary of the project organization, schedule and technical program is included. (Author)

  17. Alternative loop rings

    CERN Document Server

    Goodaire, EG; Polcino Milies, C

    1996-01-01

    For the past ten years, alternative loop rings have intrigued mathematicians from a wide cross-section of modern algebra. As a consequence, the theory of alternative loop rings has grown tremendously. One of the main developments is the complete characterization of loops which have an alternative but not associative, loop ring. Furthermore, there is a very close relationship between the algebraic structures of loop rings and of group rings over 2-groups. Another major topic of research is the study of the unit loop of the integral loop ring. Here the interaction between loop rings and group ri

  18. Extracellular calcium sensing and extracellular calcium signaling

    Science.gov (United States)

    Brown, E. M.; MacLeod, R. J.; O'Malley, B. W. (Principal Investigator)

    2001-01-01

    The cloning of a G protein-coupled extracellular Ca(2+) (Ca(o)(2+))-sensing receptor (CaR) has elucidated the molecular basis for many of the previously recognized effects of Ca(o)(2+) on tissues that maintain systemic Ca(o)(2+) homeostasis, especially parathyroid chief cells and several cells in the kidney. The availability of the cloned CaR enabled the development of DNA and antibody probes for identifying the CaR's mRNA and protein, respectively, within these and other tissues. It also permitted the identification of human diseases resulting from inactivating or activating mutations of the CaR gene and the subsequent generation of mice with targeted disruption of the CaR gene. The characteristic alterations in parathyroid and renal function in these patients and in the mice with "knockout" of the CaR gene have provided valuable information on the CaR's physiological roles in these tissues participating in mineral ion homeostasis. Nevertheless, relatively little is known about how the CaR regulates other tissues involved in systemic Ca(o)(2+) homeostasis, particularly bone and intestine. Moreover, there is evidence that additional Ca(o)(2+) sensors may exist in bone cells that mediate some or even all of the known effects of Ca(o)(2+) on these cells. Even more remains to be learned about the CaR's function in the rapidly growing list of cells that express it but are uninvolved in systemic Ca(o)(2+) metabolism. Available data suggest that the receptor serves numerous roles outside of systemic mineral ion homeostasis, ranging from the regulation of hormonal secretion and the activities of various ion channels to the longer term control of gene expression, programmed cell death (apoptosis), and cellular proliferation. In some cases, the CaR on these "nonhomeostatic" cells responds to local changes in Ca(o)(2+) taking place within compartments of the extracellular fluid (ECF) that communicate with the outside environment (e.g., the gastrointestinal tract). In others

  19. The finite Bruck Loops

    CERN Document Server

    Baumeister, Barbara

    2009-01-01

    We continue the work by Aschbacher, Kinyon and Phillips [AKP] as well as of Glauberman [Glaub1,2] by describing the structure of the finite Bruck loops. We show essentially that a finite Bruck loop $X$ is the direct product of a Bruck loop of odd order with either a soluble Bruck loop of 2-power order or a product of loops related to the groups $PSL_2(q)$, $q= 9$ or $q \\geq 5$ a Fermat prime. The latter possibillity does occur as is shown in [Nag1, BS]. As corollaries we obtain versions of Sylow's, Lagrange's and Hall's Theorems for loops.

  20. Extracellular Gd-CA

    DEFF Research Database (Denmark)

    Thomsen, Henrik S; Marckmann, Peter

    2008-01-01

    Until recently it was believed that extracellular gadolinium-based contrast agents were safe for both the kidneys and all other organs within the dose range up to 0.3 mmol/kg body weight. However, in 2006, it was demonstrated that some gadolinium-based contrast agents may trig the development of ...

  1. Pseudonoise code tracking loop

    Science.gov (United States)

    Laflame, D. T. (Inventor)

    1980-01-01

    A delay-locked loop is presented for tracking a pseudonoise (PN) reference code in an incoming communication signal. The loop is less sensitive to gain imbalances, which can otherwise introduce timing errors in the PN reference code formed by the loop.

  2. Panning and identification of antagonistic active peptides specifically bin-ding to the first and second extracellular membrane loops of rat CCR5 by technique of phage display peptide library%应用噬菌体展示肽库技术淘选大鼠 CCR5膜外第一、二胞外环特异性结合的活性拮抗肽与初步鉴定

    Institute of Scientific and Technical Information of China (English)

    刘思雪; 胡梅; 叶小研; 黄花荣; 钟英强

    2015-01-01

    [ ABSTRACT] AIM: To pan the active peptides which specifically bound to the first and second extracellular membrane loops of rat CC chemokine receptor 5 ( CCR5 ) .METHODS: The technique of phage display peptide library was used and binding ability of the peptides was identified.The amino acid sequences of the first and second extracellular loops of rat CCR5 were searched in the protein database and chemically synthesized corresponding linear peptides were used as targets in the biopanning.After 3 to 4 rounds of screening with Ph.D.TM-7 Phage Display Peptide Library were per-formed, the specific phages were collected and primarily identified by ELISA.RESULTS:The sequences of the peptides displayed on the selected phages were GHWKVWL and HYIDFRW, both of them exhibited positive in phage binding ELISA and the binding to phages and targets were concentration dependent and saturable.CONCLUSION:Two antagonis-tic active peptides specifically binding to CCR5 were successfully obtained by the technique of phage display peptide librar-y, and the binding ability to the first and second extracellular membrane loops of rat CCR5 were proved in vitro.%目的:利用噬菌体展示肽库技术淘选与大鼠CC趋化因子受体5( CCR5)膜外第一、二胞外环特异性结合的短肽,并鉴定其与CCR5的结合能力。方法:在蛋白质数据库中查得大鼠CCR5第一、二胞外环的氨基酸序列,合成相应的线性短肽作为淘选的靶分子,利用噬菌体展示7肽文库进行3~4轮淘选,用ELISA法鉴定所选肽与靶分子的结合,并测定其与浓度的关系。结果:与CCR5第一、二胞外环特异性结合的噬菌体展示的短肽序列分别为GHWKVWL和HYIDFRW,ELISA鉴定呈阳性反应,且短肽与靶分子的结合具有浓度依赖性和可饱和性。结论:利用噬菌体展示技术成功获得了2条CCR5特异性结合的短肽,并在体外证明其可与CCR5第一、二胞外环具有结合能力。

  3. Supersymmetric Wilson loops at two loops

    CERN Document Server

    Bassetto, Antonio; Pucci, Fabrizio; Seminara, Domenico

    2008-01-01

    We study the quantum properties of certain BPS Wilson loops in ${\\cal N}=4$ supersymmetric Yang-Mills theory. They belong to a general family, introduced recently, in which the addition of particular scalar couplings endows generic loops on $S^3$ with a fraction of supersymmetry. When restricted to $S^2$, their quantum average has been further conjectured to be exactly computed by the matrix model governing the zero-instanton sector of YM$_2$ on the sphere. We perform a complete two-loop analysis on a class of cusped Wilson loops lying on a two-dimensional sphere, finding perfect agreement with the conjecture. The perturbative computation reproduces the matrix-model expectation through a highly non-trivial interplay between ladder diagrams and self-energies/vertex contributions, suggesting the existence of a localization procedure.

  4. Cosmic string loop shapes

    CERN Document Server

    Blanco-Pillado, Jose J; Shlaer, Benjamin

    2015-01-01

    We analyze the shapes of cosmic string loops found in large-scale simulations of an expanding-universe string network. The simulation does not include gravitational back reaction, but we model that process by smoothing the loop using Lorentzian convolution. We find that loops at formation consist of generally straight segments separated by kinks. We do not see cusps or any cusp-like structure at the scale of the entire loop, although we do see very small regions of string that move with large Lorentz boosts. However, smoothing of the string almost always introduces two cusps on each loop. The smoothing process does not lead to any significant fragmentation of loops that were in non-self-intersecting trajectories before smoothing.

  5. Coxeter-Chein Loops

    CERN Document Server

    Blok, Rieuwert J

    2011-01-01

    In 1974 Orin Chein discovered a new family of Moufang loops which are now called Chein loops. Such a loop can be created from any group $W$ together with $\\mathbb{Z}_2$ by a variation on a semi-direct product. We study these loops in the case where $W$ is a Coxeter group and show that it has what we call a Chein-Coxeter system, a small set of generators of order 2, together with a set of relations closely related to the Coxeter relations and Chein relations. As a result we are able to give amalgam presentations for Coxeter-Chein loops. This is to our knowledge the first such presentation for a Moufang loop.

  6. Coxeter-Chein Loops

    OpenAIRE

    Blok, Rieuwert J.; Gagola III, Stephen

    2011-01-01

    In 1974 Orin Chein discovered a new family of Moufang loops which are now called Chein loops. Such a loop can be created from any group $W$ together with $\\mathbb{Z}_2$ by a variation on a semi-direct product. We study these loops in the case where $W$ is a Coxeter group and show that it has what we call a Chein-Coxeter system, a small set of generators of order 2, together with a set of relations closely related to the Coxeter relations and Chein relations. As a result we are able to give am...

  7. Observational Evidence for Loop-Loop Interaction

    Science.gov (United States)

    Guiping, W.; Guangli, H.; Yuhua, T.; Aoao, X.

    2004-01-01

    Through analysis of the data including the hard x-ray(BASTE) microwave(NoRP) and magnetogram(MDI from SOHO) as well as the images of soft x-ray(YHKOH) and EIT(SOHO) on Apr. 151998 solar flare in the active region 8203(N30W12) we found: (1) there are similar quasi period oscillation in the profile of hard x-ray flux (25-5050-100keV) and microwave flux(1GHz) with duration of 85+/-25s every peak includes two sub-peak structures; (2) in the preheat phase of the flare active magnetic field changes apparently and a s-pole spot emerges ; (3) several EIT and soft x-ray loops exist and turn into bright . All of these may suggest that loop-loop interaction indeed exist. Through reconnection the electrons may be accelerated and the hard x-ray and microwave emission take place.

  8. Extracellular Matrix Proteins

    Directory of Open Access Journals (Sweden)

    Linda Christian Carrijo-Carvalho

    2012-01-01

    Full Text Available Lipocalin family members have been implicated in development, regeneration, and pathological processes, but their roles are unclear. Interestingly, these proteins are found abundant in the venom of the Lonomia obliqua caterpillar. Lipocalins are β-barrel proteins, which have three conserved motifs in their amino acid sequence. One of these motifs was shown to be a sequence signature involved in cell modulation. The aim of this study is to investigate the effects of a synthetic peptide comprising the lipocalin sequence motif in fibroblasts. This peptide suppressed caspase 3 activity and upregulated Bcl-2 and Ki-67, but did not interfere with GPCR calcium mobilization. Fibroblast responses also involved increased expression of proinflammatory mediators. Increase of extracellular matrix proteins, such as collagen, fibronectin, and tenascin, was observed. Increase in collagen content was also observed in vivo. Results indicate that modulation effects displayed by lipocalins through this sequence motif involve cell survival, extracellular matrix remodeling, and cytokine signaling. Such effects can be related to the lipocalin roles in disease, development, and tissue repair.

  9. What Controls DNA Looping?

    Directory of Open Access Journals (Sweden)

    Pamela J. Perez

    2014-08-01

    Full Text Available The looping of DNA provides a means of communication between sequentially distant genomic sites that operate in tandem to express, copy, and repair the information encoded in the DNA base sequence. The short loops implicated in the expression of bacterial genes suggest that molecular factors other than the naturally stiff double helix are involved in bringing the interacting sites into close spatial proximity. New computational techniques that take direct account of the three-dimensional structures and fluctuations of protein and DNA allow us to examine the likely means of enhancing such communication. Here, we describe the application of these approaches to the looping of a 92 base-pair DNA segment between the headpieces of the tetrameric Escherichia coli Lac repressor protein. The distortions of the double helix induced by a second protein—the nonspecific nucleoid protein HU—increase the computed likelihood of looping by several orders of magnitude over that of DNA alone. Large-scale deformations of the repressor, sequence-dependent features in the DNA loop, and deformability of the DNA operators also enhance looping, although to lesser degrees. The correspondence between the predicted looping propensities and the ease of looping derived from gene-expression and single-molecule measurements lends credence to the derived structural picture.

  10. Testing loop quantum cosmology

    Science.gov (United States)

    Wilson-Ewing, Edward

    2017-03-01

    Loop quantum cosmology predicts that quantum gravity effects resolve the big-bang singularity and replace it by a cosmic bounce. Furthermore, loop quantum cosmology can also modify the form of primordial cosmological perturbations, for example by reducing power at large scales in inflationary models or by suppressing the tensor-to-scalar ratio in the matter bounce scenario; these two effects are potential observational tests for loop quantum cosmology. In this article, I review these predictions and others, and also briefly discuss three open problems in loop quantum cosmology: its relation to loop quantum gravity, the trans-Planckian problem, and a possible transition from a Lorentzian to a Euclidean space-time around the bounce point.

  11. Extracellular matrix structure.

    Science.gov (United States)

    Theocharis, Achilleas D; Skandalis, Spyros S; Gialeli, Chrysostomi; Karamanos, Nikos K

    2016-02-01

    Extracellular matrix (ECM) is a non-cellular three-dimensional macromolecular network composed of collagens, proteoglycans/glycosaminoglycans, elastin, fibronectin, laminins, and several other glycoproteins. Matrix components bind each other as well as cell adhesion receptors forming a complex network into which cells reside in all tissues and organs. Cell surface receptors transduce signals into cells from ECM, which regulate diverse cellular functions, such as survival, growth, migration, and differentiation, and are vital for maintaining normal homeostasis. ECM is a highly dynamic structural network that continuously undergoes remodeling mediated by several matrix-degrading enzymes during normal and pathological conditions. Deregulation of ECM composition and structure is associated with the development and progression of several pathologic conditions. This article emphasizes in the complex ECM structure as to provide a better understanding of its dynamic structural and functional multipotency. Where relevant, the implication of the various families of ECM macromolecules in health and disease is also presented.

  12. Natively unstructured loops differ from other loops.

    Directory of Open Access Journals (Sweden)

    Avner Schlessinger

    2007-07-01

    Full Text Available Natively unstructured or disordered protein regions may increase the functional complexity of an organism; they are particularly abundant in eukaryotes and often evade structure determination. Many computational methods predict unstructured regions by training on outliers in otherwise well-ordered structures. Here, we introduce an approach that uses a neural network in a very different and novel way. We hypothesize that very long contiguous segments with nonregular secondary structure (NORS regions differ significantly from regular, well-structured loops, and that a method detecting such features could predict natively unstructured regions. Training our new method, NORSnet, on predicted information rather than on experimental data yielded three major advantages: it removed the overlap between testing and training, it systematically covered entire proteomes, and it explicitly focused on one particular aspect of unstructured regions with a simple structural interpretation, namely that they are loops. Our hypothesis was correct: well-structured and unstructured loops differ so substantially that NORSnet succeeded in their distinction. Benchmarks on previously used and new experimental data of unstructured regions revealed that NORSnet performed very well. Although it was not the best single prediction method, NORSnet was sufficiently accurate to flag unstructured regions in proteins that were previously not annotated. In one application, NORSnet revealed previously undetected unstructured regions in putative targets for structural genomics and may thereby contribute to increasing structural coverage of large eukaryotic families. NORSnet found unstructured regions more often in domain boundaries than expected at random. In another application, we estimated that 50%-70% of all worm proteins observed to have more than seven protein-protein interaction partners have unstructured regions. The comparative analysis between NORSnet and DISOPRED2 suggested

  13. Natively unstructured loops differ from other loops.

    Science.gov (United States)

    Schlessinger, Avner; Liu, Jinfeng; Rost, Burkhard

    2007-07-01

    Natively unstructured or disordered protein regions may increase the functional complexity of an organism; they are particularly abundant in eukaryotes and often evade structure determination. Many computational methods predict unstructured regions by training on outliers in otherwise well-ordered structures. Here, we introduce an approach that uses a neural network in a very different and novel way. We hypothesize that very long contiguous segments with nonregular secondary structure (NORS regions) differ significantly from regular, well-structured loops, and that a method detecting such features could predict natively unstructured regions. Training our new method, NORSnet, on predicted information rather than on experimental data yielded three major advantages: it removed the overlap between testing and training, it systematically covered entire proteomes, and it explicitly focused on one particular aspect of unstructured regions with a simple structural interpretation, namely that they are loops. Our hypothesis was correct: well-structured and unstructured loops differ so substantially that NORSnet succeeded in their distinction. Benchmarks on previously used and new experimental data of unstructured regions revealed that NORSnet performed very well. Although it was not the best single prediction method, NORSnet was sufficiently accurate to flag unstructured regions in proteins that were previously not annotated. In one application, NORSnet revealed previously undetected unstructured regions in putative targets for structural genomics and may thereby contribute to increasing structural coverage of large eukaryotic families. NORSnet found unstructured regions more often in domain boundaries than expected at random. In another application, we estimated that 50%-70% of all worm proteins observed to have more than seven protein-protein interaction partners have unstructured regions. The comparative analysis between NORSnet and DISOPRED2 suggested that long

  14. Introduction to Loop Heat Pipes

    Science.gov (United States)

    Ku, Jentung

    2015-01-01

    This is the presentation file for the short course Introduction to Loop Heat Pipes, to be conducted at the 2015 Thermal Fluids and Analysis Workshop, August 3-7, 2015, Silver Spring, Maryland. This course will discuss operating principles and performance characteristics of a loop heat pipe. Topics include: 1) pressure profiles in the loop; 2) loop operating temperature; 3) operating temperature control; 4) loop startup; 4) loop shutdown; 5) loop transient behaviors; 6) sizing of loop components and determination of fluid inventory; 7) analytical modeling; 8) examples of flight applications; and 9) recent LHP developments.

  15. A loop quantum multiverse?

    CERN Document Server

    Bojowald, Martin

    2013-01-01

    Inhomogeneous space-times in loop quantum cosmology have come under better control with recent advances in effective methods. Even highly inhomogeneous situations, for which multiverse scenarios provide extreme examples, can now be considered at least qualitatively.

  16. Blind loop syndrome

    Science.gov (United States)

    ... part of the stomach) and operations for extreme obesity As a complication of inflammatory bowel disease Diseases such as diabetes or scleroderma may slow down movement in a segment of the intestine, leading to blind loop syndrome.

  17. Diffusion of Wilson Loops

    CERN Document Server

    Brzoska, A M; Negele, J W; Thies, M

    2004-01-01

    A phenomenological analysis of the distribution of Wilson loops in SU(2) Yang-Mills theory is presented in which Wilson loop distributions are described as the result of a diffusion process on the group manifold. It is shown that, in the absence of forces, diffusion implies Casimir scaling and, conversely, exact Casimir scaling implies free diffusion. Screening processes occur if diffusion takes place in a potential. The crucial distinction between screening of fundamental and adjoint loops is formulated as a symmetry property related to the center symmetry of the underlying gauge theory. The results are expressed in terms of an effective Wilson loop action and compared with various limits of SU(2) Yang-Mills theory.

  18. From Loops to Surfaces

    CERN Document Server

    Neuberger, H

    2010-01-01

    The generating function for all antisymmetric characters of a Wilson loop matrix in SU(N) Yang Mills theory is the partition function of a fermion living on the curve describing the loop. This generalizes to fermion subsystems living on higher dimensional submanifolds, for example, surfaces. This write-up also contains some extra background, in response to some questions raised during the oral presentation.

  19. Genetic Programming with Simple Loops

    Institute of Scientific and Technical Information of China (English)

    QI Yuesheng; WANG Baozhong; KANG Lishan

    1999-01-01

    A kind of loop function LoopN inGenetic Programming (GP) is proposed.Different from other forms of loopfunction, such as While-Do and Repeat-Until, LoopNtakes only oneargument as its loop body and makes its loop body simply run N times,soinfinite loops will never happen. The problem of how to avoid too manylayers ofloops in Genetic Programming is also solved. The advantage ofLoopN in GP is shown bythe computational results in solving the mowerproblem.

  20. Loop electrosurgical excisional procedure.

    Science.gov (United States)

    Mayeaux, E J; Harper, M B

    1993-02-01

    Loop electrosurgical excisional procedure, or LEEP, also known as loop diathermy treatment, loop excision of the transformation zone (LETZ), and large loop excision of the transformation zone (LLETZ), is a new technique for outpatient diagnosis and treatment of dysplastic cervical lesions. This procedure produces good specimens for cytologic evaluation, carries a low risk of affecting childbearing ability, and is likely to replace cryotherapy or laser treatment for cervical neoplasias. LEEP uses low-current, high-frequency electrical generators and thin stainless steel or tungsten loops to excise either lesions or the entire transformation zone. Complication rates are comparable to cryotherapy or laser treatment methods and include bleeding, incomplete removal of the lesion, and cervical stenosis. Compared with other methods, the advantages of LEEP include: removal of abnormal tissue in a manner permitting cytologic study, low cost, ease of acquiring necessary skills, and the ability to treat lesions with fewer visits. Patient acceptance of the procedure is high. Widespread use of LEEP by family physicians can be expected.

  1. Closed-loop, open-source electrophysiology

    Directory of Open Access Journals (Sweden)

    John D Rolston

    2010-09-01

    Full Text Available Multiple extracellular microelectrodes (multi-electrode arrays, or MEAs effectively record rapidly varying neural signals, and can also be used for electrical stimulation. Multi-electrode recording can serve as artificial output (efferents from a neural system, while complex spatially and temporally targeted stimulation can serve as artificial input (afferents to the neuronal network. Multi-unit or local field potential recordings can not only be used to control real world artifacts, such as prostheses, computers or robots, but can also trigger or alter subsequent stimulation. Real-time feedback stimulation may serve to modulate or normalize aberrant neural activity, to induce plasticity, or to serve as artificial sensory input. Despite promising closed-loop applications, commercial electrophysiology systems do not yet take advantage of the bidirectional capabilities of multi-electrodes, especially for use in freely moving animals. We addressed this lack of tools for closing the loop with NeuroRighter, an open-source system including recording hardware, stimulation hardware, and control software with a graphical user interface. The integrated system is capable of multi-electrode recording and simultaneous patterned microstimulation triggered by recordings with minimal stimulation artifact. The potential applications of closed-loop systems as research tools and clinical treatments are broad; we provide one example where epileptic activity recorded by a multi-electrode probe is used to trigger targeted stimulation, via that probe, to freely moving rodents.

  2. Molecular mechanism of Zn2+ agonism in the extracellular domain of GPR39

    DEFF Research Database (Denmark)

    Storjohann, Laura; Holst, Birgitte; Schwartz, Thue W

    2008-01-01

    -terminal segment. Surprisingly, substitution of Asp313 located in extracellular loop 3 greatly increased ligand-independent signaling and apparently eliminated Zn2+-induced activation. It is proposed that Zn2+ acts as an agonist for GPR39, not in the classical manner by directly stabilizing an active conformation...

  3. Extracellular vesicles for drug delivery

    NARCIS (Netherlands)

    Vader, Pieter; Mol, Emma A; Pasterkamp, Gerard; Schiffelers, Raymond M

    Extracellular vesicles (EVs) are cell-derived membrane vesicles, and represent an endogenous mechanism for intercellular communication. Since the discovery that EVs are capable of functionally transferring biological information, the potential use of EVs as drug delivery vehicles has gained

  4. Loops in Twistor Space

    CERN Document Server

    Bena, I; Kosower, D A; Roiban, R; Bena, Iosif; Bern, Zvi; Kosower, David A.; Roiban, Radu

    2004-01-01

    We elucidate the one-loop twistor-space structure corresponding to momentum-space MHV diagrams. We also discuss the infrared divergences, and argue that only a limited set of MHV diagrams contain them. We show how to introduce a twistor-space regulator corresponding to dimensional regularization for the infrared-divergent diagrams. We also evaluate explicitly the `holomorphic anomaly' pointed out by Cachazo, Svrcek, and Witten, and use the result to define modified differential operators which can be used to probe the twistor-space structure of one-loop amplitudes.

  5. Closed Loop Subspace Identification

    Directory of Open Access Journals (Sweden)

    Geir W. Nilsen

    2005-07-01

    Full Text Available A new three step closed loop subspace identifications algorithm based on an already existing algorithm and the Kalman filter properties is presented. The Kalman filter contains noise free states which implies that the states and innovation are uneorre lated. The idea is that a Kalman filter found by a good subspace identification algorithm will give an output which is sufficiently uncorrelated with the noise on the output of the actual process. Using feedback from the output of the estimated Kalman filter in the closed loop system a subspace identification algorithm can be used to estimate an unbiased model.

  6. Loop Quantum Gravity

    CERN Document Server

    Chiou, Dah-Wei

    2014-01-01

    This article presents an "in-a-nutshell" yet self-contained introductory review on loop quantum gravity (LQG) -- a background-independent, nonperturbative approach to a consistent quantum theory of gravity. Instead of rigorous and systematic derivations, it aims to provide a general picture of LQG, placing emphasis on the fundamental ideas and their significance. The canonical formulation of LQG, as the central topic of the article, is presented in a logically orderly fashion with moderate details, while the spin foam theory, black hole thermodynamics, and loop quantum cosmology are covered briefly. Current directions and open issues are also summarized.

  7. Optimizing analog-to-digital converters for sampling extracellular potentials.

    Science.gov (United States)

    Artan, N Sertac; Xu, Xiaoxiang; Shi, Wei; Chao, H Jonathan

    2012-01-01

    In neural implants, an analog-to-digital converter (ADC) provides the delicate interface between the analog signals generated by neurological processes and the digital signal processor that is tasked to interpret these signals for instance for epileptic seizure detection or limb control. In this paper, we propose a low-power ADC architecture for neural implants that process extracellular potentials. The proposed architecture uses the spike detector that is readily available on most of these implants in a closed-loop with an ADC. The spike detector determines whether the current input signal is part of a spike or it is part of noise to adaptively determine the instantaneous sampling rate of the ADC. The proposed architecture can reduce the power consumption of a traditional ADC by 62% when sampling extracellular potentials without any significant impact on spike detection accuracy.

  8. Loop Quantum Gravity

    Directory of Open Access Journals (Sweden)

    Rovelli Carlo

    1998-01-01

    Full Text Available The problem of finding the quantum theory of the gravitational field, and thus understanding what is quantum spacetime, is still open. One of the most active of the current approaches is loop quantum gravity. Loop quantum gravity is a mathematically well-defined, non-perturbative and background independent quantization of general relativity, with its conventional matter couplings. Research in loop quantum gravity today forms a vast area, ranging from mathematical foundations to physical applications. Among the most significant results obtained are: (i The computation of the physical spectra of geometrical quantities such as area and volume, which yields quantitative predictions on Planck-scale physics. (ii A derivation of the Bekenstein-Hawking black hole entropy formula. (iii An intriguing physical picture of the microstructure of quantum physical space, characterized by a polymer-like Planck scale discreteness. This discreteness emerges naturally from the quantum theory and provides a mathematically well-defined realization of Wheeler's intuition of a spacetime ``foam''. Long standing open problems within the approach (lack of a scalar product, over-completeness of the loop basis, implementation of reality conditions have been fully solved. The weak part of the approach is the treatment of the dynamics: at present there exist several proposals, which are intensely debated. Here, I provide a general overview of ideas, techniques, results and open problems of this candidate theory of quantum gravity, and a guide to the relevant literature.

  9. Reversible hysteresis loop tuning

    Science.gov (United States)

    Berger, A.; Binek, Ch.; Margulies, D. T.; Moser, A.; Fullerton, E. E.

    2006-02-01

    We utilize antiferromagnetically coupled bilayer structures to magnetically tune hysteresis loop properties. Key element of this approach is the non-overlapping switching field distribution of the two magnetic layers that make up the system: a hard magnetic CoPtCrB layer (HL) and a soft magnetic CoCr layer (SL). Both layers are coupled antiferromagnetically through an only 0.6-nm-thick Ru interlayer. The non-overlapping switching field distribution allows the measurement of magnetization reversal in the SL at low fields while keeping the magnetization state of the HL unperturbed. Applying an appropriate high field or high field sequence changes the magnetic state of the HL, which then influences the SL magnetization reversal due to the interlayer coupling. In this way, the position and shape of the SL hysteresis loop can be changed or tuned in a fully reversible and highly effective manner. Here, we study specifically how the SL hysteresis loop characteristics change as we move the HL through an entire high field hysteresis loop sequence.

  10. Principles of agonist recognition in Cys-loop receptors

    Directory of Open Access Journals (Sweden)

    Timothy eLynagh

    2014-04-01

    Full Text Available Cys-loop receptors are ligand-gated ion channels that are activated by a structurally diverse array of neurotransmitters, including acetylcholine, serotonin, glycine and GABA. After the term chemoreceptor emerged over 100 years ago, there was some wait until affinity labeling, molecular cloning, functional studies and X-ray crystallography experiments identified the extracellular interface of adjacent subunits as the principal site of agonist binding. The question of how subtle differences at and around agonist-binding sites of different Cys-loop receptors can accommodate transmitters as chemically diverse as glycine and serotonin has been subject to intense research over the last three decades. This review outlines the functional diversity and current structural understanding of agonist-binding sites, including those of invertebrate Cys-loop receptors. Together, this provides a framework to understand the atomic determinants involved in how these valuable therapeutic targets recognize and bind their ligands.

  11. Two-loop and n-loop eikonal vertex corrections

    OpenAIRE

    Kidonakis, Nikolaos

    2003-01-01

    I present calculations of two-loop vertex corrections with massive and massless partons in the eikonal approximation. I show that the $n$-loop result for the UV poles can be given in terms of the one-loop calculation.

  12. Local loop near-rings

    OpenAIRE

    Franetič, Damir

    2015-01-01

    We study loop near-rings, a generalization of near-rings, where the additive structure is not necessarily associative. We introduce local loop near-rings and prove a useful detection principle for localness.

  13. On the extended loop calculus

    CERN Document Server

    Griego, J R

    1995-01-01

    Some features of extended loops are considered. In particular, the behaviour under diffeomorphism transformations of the wavefunctions with support on the extended loop space are studied. The basis of a method to obtain analytical expressions of diffeomorphism invariants via extended loops are settled. Applications to knot theory and quantum gravity are considered.

  14. Closing global material loops

    DEFF Research Database (Denmark)

    Prosman, Ernst-Jan; Wæhrens, Brian Vejrum; Liotta, Giacomo

    2017-01-01

    Replacing virgin materials with waste materials, a practice known as Industrial Symbiosis (IS), has been identified as a key strategy for closing material loops. This article adopts a critical view on geographic proximity and external coordinators – two key enablers of IS. By ‘uncovering’ a case...... where both enablers are absent, this study seeks to explore firm-level challenges of IS. We adopt an exploratory case study approach at a cement manufacturer who engages in cross-border IS without the support of external coordinators. Our research presents insights into two key areas of IS: 1) setting...... for geographic proximity and external coordinators. In doing so, our insights into firm-level challenges of long-distance IS exchanges contribute to closing global material loops by increasing the number of potential circular pathways....

  15. Loop Quantum Cosmology

    Directory of Open Access Journals (Sweden)

    Bojowald Martin

    2008-07-01

    Full Text Available Quantum gravity is expected to be necessary in order to understand situations in which classical general relativity breaks down. In particular in cosmology one has to deal with initial singularities, i.e., the fact that the backward evolution of a classical spacetime inevitably comes to an end after a finite amount of proper time. This presents a breakdown of the classical picture and requires an extended theory for a meaningful description. Since small length scales and high curvatures are involved, quantum effects must play a role. Not only the singularity itself but also the surrounding spacetime is then modified. One particular theory is loop quantum cosmology, an application of loop quantum gravity to homogeneous systems, which removes classical singularities. Its implications can be studied at different levels. The main effects are introduced into effective classical equations, which allow one to avoid the interpretational problems of quantum theory. They give rise to new kinds of early-universe phenomenology with applications to inflation and cyclic models. To resolve classical singularities and to understand the structure of geometry around them, the quantum description is necessary. Classical evolution is then replaced by a difference equation for a wave function, which allows an extension of quantum spacetime beyond classical singularities. One main question is how these homogeneous scenarios are related to full loop quantum gravity, which can be dealt with at the level of distributional symmetric states. Finally, the new structure of spacetime arising in loop quantum gravity and its application to cosmology sheds light on more general issues, such as the nature of time.

  16. Loop Quantum Cosmology

    Directory of Open Access Journals (Sweden)

    Bojowald Martin

    2005-12-01

    Full Text Available Quantum gravity is expected to be necessary in order to understand situations where classical general relativity breaks down. In particular in cosmology one has to deal with initial singularities, i.e., the fact that the backward evolution of a classical space-time inevitably comes to an end after a finite amount of proper time. This presents a breakdown of the classical picture and requires an extended theory for a meaningful description. Since small length scales and high curvatures are involved, quantum effects must play a role. Not only the singularity itself but also the surrounding space-time is then modified. One particular realization is loop quantum cosmology, an application of loop quantum gravity to homogeneous systems, which removes classical singularities. Its implications can be studied at different levels. Main effects are introduced into effective classical equations which allow to avoid interpretational problems of quantum theory. They give rise to new kinds of early universe phenomenology with applications to inflation and cyclic models. To resolve classical singularities and to understand the structure of geometry around them, the quantum description is necessary. Classical evolution is then replaced by a difference equation for a wave function which allows to extend space-time beyond classical singularities. One main question is how these homogeneous scenarios are related to full loop quantum gravity, which can be dealt with at the level of distributional symmetric states. Finally, the new structure of space-time arising in loop quantum gravity and its application to cosmology sheds new light on more general issues such as time.

  17. PAR Loop Schedule Review

    Energy Technology Data Exchange (ETDEWEB)

    Schaffer, Jr.; W.F.

    1958-04-30

    The schedule for the installation of the PAR slurry loop experiment in the South Facility of the ORR has been reviewed and revised. The design, fabrications and Installation is approximately two weeks behind schedule at this time due to many factors; however, indications are that this time can be made up. Design is estimated to be 75% complete, fabrication 32% complete and installation 12% complete.

  18. Verification of Loop Diagnostics

    Science.gov (United States)

    Winebarger, A.; Lionello, R.; Mok, Y.; Linker, J.; Mikic, Z.

    2014-01-01

    Many different techniques have been used to characterize the plasma in the solar corona: density-sensitive spectral line ratios are used to infer the density, the evolution of coronal structures in different passbands is used to infer the temperature evolution, and the simultaneous intensities measured in multiple passbands are used to determine the emission measure. All these analysis techniques assume that the intensity of the structures can be isolated through background subtraction. In this paper, we use simulated observations from a 3D hydrodynamic simulation of a coronal active region to verify these diagnostics. The density and temperature from the simulation are used to generate images in several passbands and spectral lines. We identify loop structures in the simulated images and calculate the loop background. We then determine the density, temperature and emission measure distribution as a function of time from the observations and compare with the true temperature and density of the loop. We find that the overall characteristics of the temperature, density, and emission measure are recovered by the analysis methods, but the details of the true temperature and density are not. For instance, the emission measure curves calculated from the simulated observations are much broader than the true emission measure distribution, though the average temperature evolution is similar. These differences are due, in part, to inadequate background subtraction, but also indicate a limitation of the analysis methods.

  19. Cosmic string loop microlensing

    Science.gov (United States)

    Bloomfield, Jolyon K.; Chernoff, David F.

    2014-06-01

    Cosmic superstring loops within the galaxy microlens background point sources lying close to the observer-string line of sight. For suitable alignments, multiple paths coexist and the (achromatic) flux enhancement is a factor of two. We explore this unique type of lensing by numerically solving for geodesics that extend from source to observer as they pass near an oscillating string. We characterize the duration of the flux doubling and the scale of the image splitting. We probe and confirm the existence of a variety of fundamental effects predicted from previous analyses of the static infinite straight string: the deficit angle, the Kaiser-Stebbins effect, and the scale of the impact parameter required to produce microlensing. Our quantitative results for dynamical loops vary by O(1) factors with respect to estimates based on infinite straight strings for a given impact parameter. A number of new features are identified in the computed microlensing solutions. Our results suggest that optical microlensing can offer a new and potentially powerful methodology for searches for superstring loop relics of the inflationary era.

  20. Extracellular vesicles for drug delivery

    NARCIS (Netherlands)

    Vader, Pieter; Mol, Emma A; Pasterkamp, Gerard; Schiffelers, Raymond M

    2016-01-01

    Extracellular vesicles (EVs) are cell-derived membrane vesicles, and represent an endogenous mechanism for intercellular communication. Since the discovery that EVs are capable of functionally transferring biological information, the potential use of EVs as drug delivery vehicles has gained consider

  1. LoopIng: a template-based tool for predicting the structure of protein loops.

    KAUST Repository

    Messih, Mario Abdel

    2015-08-06

    Predicting the structure of protein loops is very challenging, mainly because they are not necessarily subject to strong evolutionary pressure. This implies that, unlike the rest of the protein, standard homology modeling techniques are not very effective in modeling their structure. However, loops are often involved in protein function, hence inferring their structure is important for predicting protein structure as well as function.We describe a method, LoopIng, based on the Random Forest automated learning technique, which, given a target loop, selects a structural template for it from a database of loop candidates. Compared to the most recently available methods, LoopIng is able to achieve similar accuracy for short loops (4-10 residues) and significant enhancements for long loops (11-20 residues). The quality of the predictions is robust to errors that unavoidably affect the stem regions when these are modeled. The method returns a confidence score for the predicted template loops and has the advantage of being very fast (on average: 1 min/loop).www.biocomputing.it/loopinganna.tramontano@uniroma1.itSupplementary data are available at Bioinformatics online.

  2. EFECTO DE LA ADMINISTRACIÓN INTRACEREBRAL DE MK-801 Y (- NICOTINA EN LAS CONCENTRACIONES EXTRACELULARES DE GLU Y GABA EN EL NÚCLEO PEDUNCULOPONTINO DE RATAS Effect of the Mk801 and (- Nicotine Intracerebral Administration on Glu and Gaba Extracellular Concentration in the Pedunculopontine Nucleus from Rats

    Directory of Open Access Journals (Sweden)

    LISETTE BLANCO LEZCANO

    Full Text Available Aunque la manipulación farmacológica de los sistemas glutamatérgico y colinérgico se ha tratado en modelos experimentales de enfermedad de Parkinson (EP, pocos autores han realizado estudios de esta temática a nivel del núcleo pedunculopontino (NPP. El presente trabajo aborda los cambios en las concentraciones extracelulares (CE de glutamato (Glu y ácido δ-amino butírico (GABA en el NPP de ratas hemiparkinsonizadas por inyección de 6-hidroxidopamina (6-OHDA y sometidas a infusión local de MK-801 (10 µmol/L o (- nicotina (10 mM. La infusión se realizó mediante microdiálisis cerebral y la determinación de CE de neurotransmisores se realizó a través de cromatografía líquida de alta resolución acoplada a detección de fluorescencia. La infusión de MK-801 en el NPP produjo disminución significativa de CE de Glu (pAlthough the pharmacological manipulation of the glutamatergic and cholinergic systems have been studied in animal models of Parkinson´s disease (PD, only some authors have done work on this topic at the pedunculopontine nucleus (PPN. The present work studied the changes in glutamate (Glu and δ-aminobutyric acid (GABA extracellular concentrations (EC in the PPN from hemiparkinsonian rats by 6hydroxydopamine injection. The rats were locally perfused by MK-801 (10 µmol/L or (- nicotine (10 mM solutions by cerebral microdyalisis. The biochemical studies were carried out through high performance liquid chromatography coupled to fluorescence detection. MK-801 infusion induced a significant decrease of Glu (p< 0.01 and GABA (p< 0.01 EC in PPN. On the other hand (- nicotine infusion induced a significant increase of Glu (p< 0.001 and GABA (p< 0.001 EC in PPN from hemiparkinsonian rats. The local blockade of NMDA receptors by MK-801 infusion facilitates the interaction between Glu and their metabotropic receptors that take part in presynaptic inhibition mechanisms and interfere with neurotransmitters release. Meanwhile, the

  3. Improving Loop Dependence Analysis

    DEFF Research Database (Denmark)

    Jensen, Nicklas Bo; Karlsson, Sven

    2017-01-01

    Programmers can no longer depend on new processors to have significantly improved single-thread performance. Instead, gains have to come from other sources such as the compiler and its optimization passes. Advanced passes make use of information on the dependencies related to loops. We improve...... the quality of that information by reusing the information given by the programmer for parallelization. We have implemented a prototype based on GCC into which we also add a new optimization pass. Our approach improves the amount of correctly classified dependencies resulting in 46% average improvement...

  4. Closing the loop.

    Science.gov (United States)

    Dassau, E; Atlas, E; Phillip, M

    2011-02-01

    Closed-loop algorithms can be found in every aspect of everyday modern life. Automation and control are used constantly to provide safety and to improve quality of life. Closed-loop systems and algorithms can be found in home appliances, automobiles, aviation and more. Can one imagine nowadays driving a car without ABS, cruise control or even anti-sliding control? Similar principles of automation and control can be used in the management of diabetes mellitus (DM). The idea of an algorithmic/technological way to control glycaemia is not new and has been researched for more than four decades. However, recent improvements in both glucose-sensing technology and insulin delivery together with advanced control and systems engineering made this dream of an artificial pancreas possible. The artificial pancreas may be the next big step in the treatment of DM since the use of insulin analogues. An artificial pancreas can be described as internal or external devices that use continuous glucose measurements to automatically manage exogenous insulin delivery with or without other hormones in an attempt to restore glucose regulation in individuals with DM using a control algorithm. This device as described can be internal or external; can use different types of control algorithms with bi-hormonal or uni-hormonal design; and can utilise different ways to administer them. The different designs and implementations have transitioned recently from in silico simulations to clinical evaluation stage with practical applications in mind. This may mark the beginning of a new era in diabetes management with the introduction of semi-closed-loop systems that can prevent or minimise nocturnal hypoglycaemia, to hybrid systems that will manage blood glucose (BG) levels with minimal user intervention to finally fully automated systems that will take the user out of the loop. More and more clinical trials will be needed for the artificial pancreas to become a reality but initial encouraging

  5. Extracellular Disulfide Bridges Serve Different Purposes in Two Homologous Chemokine Receptors, CCR1 and CCR5

    DEFF Research Database (Denmark)

    Rummel, Pia Cwarzko; Thiele, Stefanie; Hansen, Laerke Smidt

    2013-01-01

    In addition to the 7TM receptor-conserved disulfide bridge between transmembrane helix (TM) 3 and extracellular loop (ECL) 2, chemokine receptors contain a disulfide bridge between the N-terminus and what previously was believed to be ECL-3. Recent crystal- and NMR-structures of CXCR4 and CXCR1...... where dispensable for small-molecule activation. This indicates that CCR5 activity is independent of extracellular regions, whereas in CCR1, preserved folding of ECL2 is necessary for activation. These results indicate that conserved structural features in a receptor subgroup, does not necessarily...

  6. Loop expansion and the bosonic representation of loop quantum gravity

    Science.gov (United States)

    Bianchi, E.; Guglielmon, J.; Hackl, L.; Yokomizo, N.

    2016-10-01

    We introduce a new loop expansion that provides a resolution of the identity in the Hilbert space of loop quantum gravity on a fixed graph. We work in the bosonic representation obtained by the canonical quantization of the spinorial formalism. The resolution of the identity gives a tool for implementing the projection of states in the full bosonic representation onto the space of solutions to the Gauss and area matching constraints of loop quantum gravity. This procedure is particularly efficient in the semiclassical regime, leading to explicit expressions for the loop expansions of coherent, heat kernel and squeezed states.

  7. Loop expansion and the bosonic representation of loop quantum gravity

    CERN Document Server

    Bianchi, Eugenio; Hackl, Lucas; Yokomizo, Nelson

    2016-01-01

    We introduce a new loop expansion that provides a resolution of the identity in the Hilbert space of loop quantum gravity on a fixed graph. We work in the bosonic representation obtained by the canonical quantization of the spinorial formalism. The resolution of the identity gives a tool for implementing the projection of states in the full bosonic representation onto the space of solutions to the Gauss and area matching constraints of loop quantum gravity. This procedure is particularly efficient in the semiclassical regime, leading to explicit expressions for the loop expansions of coherent, heat kernel and squeezed states.

  8. Extracellular vesicles: Exosomes, microvesicles, and friends

    NARCIS (Netherlands)

    Raposo, G.; Stoorvogel, W.|info:eu-repo/dai/nl/074352385

    2013-01-01

    Cells release into the extracellular environment diverse types of membrane vesicles of endosomal and plasma membrane origin called exosomes and microvesicles, respectively. These extracellular vesicles (EVs) represent an important mode of intercellular communication by serving as vehicles for

  9. Extracellular enzyme kinetics scale with resource availability

    Science.gov (United States)

    Microbial community metabolism relies on external digestion, mediated by extracellular enzymes that break down complex organic matter into molecules small enough for cells to assimilate. We analyzed the kinetics of 40 extracellular enzymes that mediate the degradation and assimi...

  10. Neutrophil Extracellular Traps and Microcrystals

    Science.gov (United States)

    2017-01-01

    Neutrophil extracellular traps represent a fascinating mechanism by which PMNs entrap extracellular microbes. The primary purpose of this innate immune mechanism is thought to localize the infection at an early stage. Interestingly, the ability of different microcrystals to induce NET formation has been recently described. Microcrystals are insoluble crystals with a size of 1–100 micrometers that have different composition and shape. Microcrystals have it in common that they irritate phagocytes including PMNs and typically trigger an inflammatory response. This review is the first to summarize observations with regard to PMN activation and NET release induced by microcrystals. Gout-causing monosodium urate crystals, pseudogout-causing calcium pyrophosphate dehydrate crystals, cholesterol crystals associated with atherosclerosis, silicosis-causing silica crystals, and adjuvant alum crystals are discussed. PMID:28373994

  11. Neutrophil Extracellular Traps and Microcrystals.

    Science.gov (United States)

    Rada, Balázs

    2017-01-01

    Neutrophil extracellular traps represent a fascinating mechanism by which PMNs entrap extracellular microbes. The primary purpose of this innate immune mechanism is thought to localize the infection at an early stage. Interestingly, the ability of different microcrystals to induce NET formation has been recently described. Microcrystals are insoluble crystals with a size of 1-100 micrometers that have different composition and shape. Microcrystals have it in common that they irritate phagocytes including PMNs and typically trigger an inflammatory response. This review is the first to summarize observations with regard to PMN activation and NET release induced by microcrystals. Gout-causing monosodium urate crystals, pseudogout-causing calcium pyrophosphate dehydrate crystals, cholesterol crystals associated with atherosclerosis, silicosis-causing silica crystals, and adjuvant alum crystals are discussed.

  12. Neutrophil Extracellular Traps and Microcrystals

    Directory of Open Access Journals (Sweden)

    Balázs Rada

    2017-01-01

    Full Text Available Neutrophil extracellular traps represent a fascinating mechanism by which PMNs entrap extracellular microbes. The primary purpose of this innate immune mechanism is thought to localize the infection at an early stage. Interestingly, the ability of different microcrystals to induce NET formation has been recently described. Microcrystals are insoluble crystals with a size of 1–100 micrometers that have different composition and shape. Microcrystals have it in common that they irritate phagocytes including PMNs and typically trigger an inflammatory response. This review is the first to summarize observations with regard to PMN activation and NET release induced by microcrystals. Gout-causing monosodium urate crystals, pseudogout-causing calcium pyrophosphate dehydrate crystals, cholesterol crystals associated with atherosclerosis, silicosis-causing silica crystals, and adjuvant alum crystals are discussed.

  13. High temperature storage loop :

    Energy Technology Data Exchange (ETDEWEB)

    Gill, David Dennis; Kolb, William J.

    2013-07-01

    A three year plan for thermal energy storage (TES) research was created at Sandia National Laboratories in the spring of 2012. This plan included a strategic goal of providing test capability for Sandia and for the nation in which to evaluate high temperature storage (>650ÀC) technology. The plan was to scope, design, and build a flow loop that would be compatible with a multitude of high temperature heat transfer/storage fluids. The High Temperature Storage Loop (HTSL) would be reconfigurable so that it was useful for not only storage testing, but also for high temperature receiver testing and high efficiency power cycle testing as well. In that way, HTSL was part of a much larger strategy for Sandia to provide a research and testing platform that would be integral for the evaluation of individual technologies funded under the SunShot program. DOEs SunShot program seeks to reduce the price of solar technologies to 6/kWhr to be cost competitive with carbon-based fuels. The HTSL project sought to provide evaluation capability for these SunShot supported technologies. This report includes the scoping, design, and budgetary costing aspects of this effort

  14. High temperature storage loop :

    Energy Technology Data Exchange (ETDEWEB)

    Gill, David Dennis; Kolb, William J.

    2013-07-01

    A three year plan for thermal energy storage (TES) research was created at Sandia National Laboratories in the spring of 2012. This plan included a strategic goal of providing test capability for Sandia and for the nation in which to evaluate high temperature storage (>650ÀC) technology. The plan was to scope, design, and build a flow loop that would be compatible with a multitude of high temperature heat transfer/storage fluids. The High Temperature Storage Loop (HTSL) would be reconfigurable so that it was useful for not only storage testing, but also for high temperature receiver testing and high efficiency power cycle testing as well. In that way, HTSL was part of a much larger strategy for Sandia to provide a research and testing platform that would be integral for the evaluation of individual technologies funded under the SunShot program. DOEs SunShot program seeks to reduce the price of solar technologies to 6/kWhr to be cost competitive with carbon-based fuels. The HTSL project sought to provide evaluation capability for these SunShot supported technologies. This report includes the scoping, design, and budgetary costing aspects of this effort

  15. Extracellular secretion of recombinant proteins

    Science.gov (United States)

    Linger, Jeffrey G.; Darzins, Aldis

    2014-07-22

    Nucleic acids encoding secretion signals, expression vectors containing the nucleic acids, and host cells containing the expression vectors are disclosed. Also disclosed are polypeptides that contain the secretion signals and methods of producing polypeptides, including methods of directing the extracellular secretion of the polypeptides. Exemplary embodiments include cellulase proteins fused to secretion signals, methods to produce and isolate these polypeptides, and methods to degrade lignocellulosic biomass.

  16. Condition Monitoring of Control Loops

    OpenAIRE

    Horch, Alexander

    2000-01-01

    The main concern of this work is the development of methodsfor automatic condition monitoring of control loops withapplication to the process industry. By condition monitoringboth detection and diagnosis of malfunctioning control loops isunderstood, using normal operating data and a minimum amount ofprocess knowledge. The use of indices for quantifying loop performance is dealtwith in the first part of the thesis. The starting point is anindex proposed by Harris (1989). This index has been mo...

  17. Loop Heat Pipe Startup Behaviors

    Science.gov (United States)

    Ku, Jentung

    2016-01-01

    A loop heat pipe must start successfully before it can commence its service. The startup transient represents one of the most complex phenomena in the loop heat pipe operation. This paper discusses various aspects of loop heat pipe startup behaviors. Topics include the four startup scenarios, the initial fluid distribution between the evaporator and reservoir that determines the startup scenario, factors that affect the fluid distribution between the evaporator and reservoir, difficulties encountered during the low power startup, and methods to enhance the startup success. Also addressed are the pressure spike and pressure surge during the startup transient, and repeated cycles of loop startup and shutdown under certain conditions.

  18. Chaperonin function depends on structure and disorder in co-chaperonin mobile loops.

    Science.gov (United States)

    Landry, S J; Steede, N K; Garaudy, A M; Maskos, K; Viitanen, P V

    1999-01-01

    Co-chaperonins from diverse organisms exhibit mobile loops which fold into a beta hairpin conformation upon binding to the chaperonin. GroES, Gp31, and human Hsp10 mobile loops exhibit a preference for the beta hairpin conformation in the free co-chaperonins, and the conformational dynamics of the human Hsp10 mobile loop appear to be restricted by nascent hairpin formation. Backbone conformational entropy must weigh against binding of co-chaperonins to chaperonins, and thus the conformational preferences of the loops may strongly influence chaperonin-binding affinity. Indeed, subtle mutations in the loops change GroEL-binding affinity and cause defects in chaperonin function, and these defects can be suppressed by mutations in GroEL which compensate for the changes in affinity. The fact that high-affinity co-chaperonin binding impairs chaperonin function has implications for the mechanism of chaperonin-assisted protein folding.

  19. Dynamic PID loop control

    Energy Technology Data Exchange (ETDEWEB)

    Pei, L.; Klebaner, A.; Theilacker, J.; Soyars, W.; Martinez, A.; Bossert, R.; DeGraff, B.; Darve, C.; /Fermilab

    2011-06-01

    The Horizontal Test Stand (HTS) SRF Cavity and Cryomodule 1 (CM1) of eight 9-cell, 1.3GHz SRF cavities are operating at Fermilab. For the cryogenic control system, how to hold liquid level constant in the cryostat by regulation of its Joule-Thompson JT-valve is very important after cryostat cool down to 2.0 K. The 72-cell cryostat liquid level response generally takes a long time delay after regulating its JT-valve; therefore, typical PID control loop should result in some cryostat parameter oscillations. This paper presents a type of PID parameter self-optimal and Time-Delay control method used to reduce cryogenic system parameters oscillation.

  20. Inductance loop and partial

    CERN Document Server

    Paul, Clayton R

    2010-01-01

    "Inductance is an unprecedented text, thoroughly discussing "loop" inductance as well as the increasingly important "partial" inductance. These concepts and their proper calculation are crucial in designing modern high-speed digital systems. World-renowned leader in electromagnetics Clayton Paul provides the knowledge and tools necessary to understand and calculate inductance." "With the present and increasing emphasis on high-speed digital systems and high-frequency analog systems, it is imperative that system designers develop an intimate understanding of the concepts and methods in this book. Inductance is a much-needed textbook designed for senior and graduate-level engineering students, as well as a hands-on guide for working engineers and professionals engaged in the design of high-speed digital and high-frequency analog systems."--Jacket.

  1. Dynamic PID loop control

    CERN Document Server

    Pei, L; Theilacker, J; Soyars, W; Martinez, A; Bossert, R; DeGraff, B; Darve, C

    2012-01-01

    The Horizontal Test Stand (HTS) SRF Cavity and Cryomodule 1 (CM1) of eight 9-cell, 1.3GHz SRF cavities are operating at Fermilab. For the cryogenic control system, how to hold liquid level constant in the cryostat by regulation of its Joule-Thompson JT-valve is very important after cryostat cool down to 2.0 K. The 72-cell cryostat liquid level response generally takes a long time delay after regulating its JT-valve; therefore, typical PID control loop should result in some cryostat parameter oscillations. This paper presents a type of PID parameter self-optimal and Time-Delay control method used to reduce cryogenic system parameters' oscillation.

  2. Vortex loops and Majoranas

    Energy Technology Data Exchange (ETDEWEB)

    Chesi, Stefano [Department of Physics, McGill University, Montreal, Quebec H3A 2T8 (Canada); CEMS, RIKEN, Wako, Saitama 351-0198 (Japan); Jaffe, Arthur [Harvard University, Cambridge, Massachusetts 02138 (United States); Department of Physics, University of Basel, Basel (Switzerland); Institute for Theoretical Physics, ETH Zürich, Zürich (Switzerland); Loss, Daniel [CEMS, RIKEN, Wako, Saitama 351-0198 (Japan); Department of Physics, University of Basel, Basel (Switzerland); Pedrocchi, Fabio L. [Department of Physics, University of Basel, Basel (Switzerland)

    2013-11-15

    We investigate the role that vortex loops play in characterizing eigenstates of interacting Majoranas. We give some general results and then focus on ladder Hamiltonian examples as a test of further ideas. Two methods yield exact results: (i) A mapping of certain spin Hamiltonians to quartic interactions of Majoranas shows that the spectra of these two examples coincide. (ii) In cases with reflection-symmetric Hamiltonians, we use reflection positivity for Majoranas to characterize vortices in the ground states. Two additional methods suggest wider applicability of these results: (iii) Numerical evidence suggests similar behavior for certain systems without reflection symmetry. (iv) A perturbative analysis also suggests similar behavior without the assumption of reflection symmetry.

  3. Loop Quantum Gravity

    Directory of Open Access Journals (Sweden)

    Rovelli Carlo

    2008-07-01

    Full Text Available The problem of describing the quantum behavior of gravity, and thus understanding quantum spacetime, is still open. Loop quantum gravity is a well-developed approach to this problem. It is a mathematically well-defined background-independent quantization of general relativity, with its conventional matter couplings. Today research in loop quantum gravity forms a vast area, ranging from mathematical foundations to physical applications. Among the most significant results obtained so far are: (i The computation of the spectra of geometrical quantities such as area and volume, which yield tentative quantitative predictions for Planck-scale physics. (ii A physical picture of the microstructure of quantum spacetime, characterized by Planck-scale discreteness. Discreteness emerges as a standard quantum effect from the discrete spectra, and provides a mathematical realization of Wheeler’s “spacetime foam” intuition. (iii Control of spacetime singularities, such as those in the interior of black holes and the cosmological one. This, in particular, has opened up the possibility of a theoretical investigation into the very early universe and the spacetime regions beyond the Big Bang. (iv A derivation of the Bekenstein–Hawking black-hole entropy. (v Low-energy calculations, yielding n-point functions well defined in a background-independent context. The theory is at the roots of, or strictly related to, a number of formalisms that have been developed for describing background-independent quantum field theory, such as spin foams, group field theory, causal spin networks, and others. I give here a general overview of ideas, techniques, results and open problems of this candidate theory of quantum gravity, and a guide to the relevant literature.

  4. Phenomenology of loop quantum cosmology

    CERN Document Server

    Sakellariadou, Mairi

    2010-01-01

    After introducing the basic ingredients of Loop Quantum Cosmology, I will briefly discuss some of its phenomenological aspects. Those can give some useful insight about the full Loop Quantum Gravity theory and provide an answer to some long-standing questions in early universe cosmology.

  5. RCD+: Fast loop modeling server.

    Science.gov (United States)

    López-Blanco, José Ramón; Canosa-Valls, Alejandro Jesús; Li, Yaohang; Chacón, Pablo

    2016-07-08

    Modeling loops is a critical and challenging step in protein modeling and prediction. We have developed a quick online service (http://rcd.chaconlab.org) for ab initio loop modeling combining a coarse-grained conformational search with a full-atom refinement. Our original Random Coordinate Descent (RCD) loop closure algorithm has been greatly improved to enrich the sampling distribution towards near-native conformations. These improvements include a new workflow optimization, MPI-parallelization and fast backbone angle sampling based on neighbor-dependent Ramachandran probability distributions. The server starts by efficiently searching the vast conformational space from only the loop sequence information and the environment atomic coordinates. The generated closed loop models are subsequently ranked using a fast distance-orientation dependent energy filter. Top ranked loops are refined with the Rosetta energy function to obtain accurate all-atom predictions that can be interactively inspected in an user-friendly web interface. Using standard benchmarks, the average root mean squared deviation (RMSD) is 0.8 and 1.4 Å for 8 and 12 residues loops, respectively, in the challenging modeling scenario in where the side chains of the loop environment are fully remodeled. These results are not only very competitive compared to those obtained with public state of the art methods, but also they are obtained ∼10-fold faster. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  6. Improved code-tracking loop

    Science.gov (United States)

    Laflame, D. T.

    1980-01-01

    Delay-locked loop tracks pseudonoise codes without introducing dc timing errors, because it is not sensitive to gain imbalance between signal processing arms. "Early" and "late" reference codes pass in combined form through both arms, and each arm acts on both codes. Circuit accomodates 1 dB weaker input signals with tracking ability equal to that of tau-dither loops.

  7. Loop groups and noncommutative geometry

    CERN Document Server

    Carpi, Sebastiano

    2015-01-01

    We describe the representation theory of loop groups in terms of K-theory and noncommutative geometry. This is done by constructing suitable spectral triples associated with the level l projective unitary positive-energy representations of any given loop group LG. The construction is based on certain supersymmetric conformal field theory models associated with LG.

  8. Brane Couplings from Bulk Loops

    OpenAIRE

    Georgi, Howard; Grant, Aaron K.; Hailu, Girma

    2000-01-01

    We compute loop corrections to the effective action of a field theory on a five-dimensional $S_1/Z_2$ orbifold. We find that the quantum loop effects of interactions in the bulk produce infinite contributions that require renormalization by four-dimensional couplings on the orbifold fixed planes. Thus bulk couplings give rise to renormalization group running of brane couplings.

  9. Higher dimensional loop quantum cosmology

    Science.gov (United States)

    Zhang, Xiangdong

    2016-07-01

    Loop quantum cosmology (LQC) is the symmetric sector of loop quantum gravity. In this paper, we generalize the structure of loop quantum cosmology to the theories with arbitrary spacetime dimensions. The isotropic and homogeneous cosmological model in n+1 dimensions is quantized by the loop quantization method. Interestingly, we find that the underlying quantum theories are divided into two qualitatively different sectors according to spacetime dimensions. The effective Hamiltonian and modified dynamical equations of n+1 dimensional LQC are obtained. Moreover, our results indicate that the classical big bang singularity is resolved in arbitrary spacetime dimensions by a quantum bounce. We also briefly discuss the similarities and differences between the n+1 dimensional model and the 3+1 dimensional one. Our model serves as a first example of higher dimensional loop quantum cosmology and offers the possibility to investigate quantum gravity effects in higher dimensional cosmology.

  10. Uranyl Nitrate Flow Loop

    Energy Technology Data Exchange (ETDEWEB)

    Ladd-Lively, Jennifer L [ORNL

    2008-10-01

    The objectives of the work discussed in this report were to: (1) develop a flow loop that would simulate the purified uranium-bearing aqueous stream exiting the solvent extraction process in a natural uranium conversion plant (NUCP); (2) develop a test plan that would simulate normal operation and disturbances that could be anticipated in an NUCP; (3) use the flow loop to test commercially available flowmeters for use as safeguards monitors; and (4) recommend a flowmeter for production-scale testing at an NUCP. There has been interest in safeguarding conversion plants because the intermediate products [uranium dioxide (UO{sub 2}), uranium tetrafluoride (UF{sub 4}), and uranium hexafluoride (UF{sub 6})] are all suitable uranium feedstocks for producing special nuclear materials. Furthermore, if safeguards are not applied virtually any nuclear weapons program can obtain these feedstocks without detection by the International Atomic Energy Agency (IAEA). Historically, IAEA had not implemented safeguards until the purified UF{sub 6} product was declared as feedstock for enrichment plants. H. A. Elayat et al. provide a basic definition of a safeguards system: 'The function of a safeguards system on a chemical conversion plant is in general terms to verify that no useful nuclear material is being diverted to use in a nuclear weapons program'. The IAEA now considers all highly purified uranium compounds as candidates for safeguarding. DOE is currently interested in 'developing instruments, tools, strategies, and methods that could be of use to the IAEA in the application of safeguards' for materials found in the front end of the nuclear fuel cycle-prior to the production of the uranium hexafluoride or oxides that have been the traditional starting point for IAEA safeguards. Several national laboratories, including Oak Ridge, Los Alamos, Lawrence Livermore, and Brookhaven, have been involved in developing tools or techniques for safeguarding conversion

  11. Extracellular nucleotide signaling in plants

    Energy Technology Data Exchange (ETDEWEB)

    Stacey, Gary [Univ. of Missouri, Columbia, MO (United States)

    2016-09-08

    Over the life of this funded project, our research group identified and characterized two key receptor proteins in plants; one mediating the innate immunity response to chitin and the other elucidating the key receptor for extracellular ATP. In the case of chitin recognition, we recently described the quaternary structure of this receptor, shedding light on how the receptor functions. Perhaps more importantly, we demonstrated that all plants have the ability to recognize both chitin oligomers and lipochitooligosacchardes, fundamentally changing how the community views the evolution of these systems and strategies that might be used, for example, to extend symbiotic nitrogen fixation to non-legumes. Our discovery of DORN1 opens a new chapter in plant physiology documenting conclusively that eATP is an important extracellular signal in plants, as it is in animals. At this point, we cannot predict just how far reaching this discovery may prove to be but we are convinced that eATP signaling is fundamental to plant growth and development and, hence, we believe that the future will be very exciting for the study of DORN1 and its overall function in plants.

  12. Modeling loop entropy.

    Science.gov (United States)

    Chirikjian, Gregory S

    2011-01-01

    Proteins fold from a highly disordered state into a highly ordered one. Traditionally, the folding problem has been stated as one of predicting "the" tertiary structure from sequential information. However, new evidence suggests that the ensemble of unfolded forms may not be as disordered as once believed, and that the native form of many proteins may not be described by a single conformation, but rather an ensemble of its own. Quantifying the relative disorder in the folded and unfolded ensembles as an entropy difference may therefore shed light on the folding process. One issue that clouds discussions of "entropy" is that many different kinds of entropy can be defined: entropy associated with overall translational and rotational Brownian motion, configurational entropy, vibrational entropy, conformational entropy computed in internal or Cartesian coordinates (which can even be different from each other), conformational entropy computed on a lattice, each of the above with different solvation and solvent models, thermodynamic entropy measured experimentally, etc. The focus of this work is the conformational entropy of coil/loop regions in proteins. New mathematical modeling tools for the approximation of changes in conformational entropy during transition from unfolded to folded ensembles are introduced. In particular, models for computing lower and upper bounds on entropy for polymer models of polypeptide coils both with and without end constraints are presented. The methods reviewed here include kinematics (the mathematics of rigid-body motions), classical statistical mechanics, and information theory.

  13. The loop gravity string

    CERN Document Server

    Freidel, Laurent; Pranzetti, Daniele

    2016-01-01

    In this work we study canonical gravity in finite regions for which we introduce a generalisation of the Gibbons-Hawking boundary term including the Immirzi parameter. We study the canonical formulation on a spacelike hypersuface with a boundary sphere and show how the presence of this term leads to an unprecedented type of degrees of freedom coming from the restoration of the gauge and diffeomorphism symmetry at the boundary. In the presence of a loop quantum gravity state, these boundary degrees of freedom localize along a set of punctures on the boundary sphere. We demonstrate that these degrees of freedom are effectively described by auxiliary strings with a 3-dimensional internal target space attached to each puncture. We show that the string currents represent the local frame field, that the string angular momenta represent the area flux and that the string stress tensor represents the two dimensional metric on the boundary of the region of interest. Finally, we show that the commutators of these broken...

  14. Hard Loops, Soft Loops, and High Density Effective Field Theory

    CERN Document Server

    Schäfer, T

    2003-01-01

    We study several issues related to the use of effective field theories in QCD at large baryon density. We show that the power counting is complicated by the appearance of two scales inside loop integrals. Hard dense loops involve the large scale $mu^2$ and lead to phenomena such as screening and damping at the scale $gmu$. Soft loops only involve small scales and lead to superfluidity and non-Fermi liquid behavior at exponentially small scales. Four-fermion operators in the effective theory are suppressed by powers of $1/mu$, but they get enhanced by hard loops. As a consequence their contribution to the pairing gap is only suppressed by powers of the coupling constant, and not powers of $1/mu$. We determine the coefficients of four-fermion operators in the effective theory by matching quark-quark scattering amplitudes. Finally, we introduce a perturbative scheme for computing corrections to the gap parameter in the superfluid phase

  15. Radial propagators and Wilson loops

    CERN Document Server

    Leupold, S; Leupold, Stefan; Weigert, Heribert

    1996-01-01

    We present a relation which connects the propagator in the radial (Fock-Schwinger) gauge with a gauge invariant Wilson loop. It is closely related to the well-known field strength formula and can be used to calculate the radial gauge propagator. The result is shown to diverge in four-dimensional space even for free fields, its singular nature is however naturally explained using the renormalization properties of Wilson loops with cusps and self-intersections. Using this observation we provide a consistent regularization scheme to facilitate loop calculations. Finally we compare our results with previous approaches to derive a propagator in Fock-Schwinger gauge.

  16. Accelerated extracellular matrix turnover during exacerbations of COPD

    DEFF Research Database (Denmark)

    Sand, Jannie M B; Knox, Alan J; Lange, Peter

    2015-01-01

    BACKGROUND: Exacerbations of chronic obstructive pulmonary disease (COPD) contribute significantly to disease progression. However, the effect on tissue structure and turnover is not well described. There is an urgent clinical need for biomarkers of disease activity associated with disease...... progression. Extracellular matrix (ECM) turnover reflects activity in tissues and consequently assessment of ECM turnover may serve as biomarkers of disease activity. We hypothesized that the turnover of lung ECM proteins were altered during exacerbations of COPD. METHODS: 69 patients with COPD hospitalised......, respectively), and degradation of elastin (ELM7 and EL-NE) and versican (VCANM). RESULTS: Circulating levels of C3M, C4M, C6M, ELM7, and EL-NE were elevated during an exacerbation of COPD as compared to follow-up (all P

  17. Analysis of extracellular RNA by digital PCR

    Directory of Open Access Journals (Sweden)

    Kenji eTakahashi

    2014-06-01

    Full Text Available The transfer of extracellular RNA is emerging as an important mechanism for intracellular communication. The ability for the transfer of functionally active RNA molecules from one cell to another within vesicles such as exosomes enables a cell to modulate cellular signaling and biological processes within recipient cells. The study of extracellular RNA requires sensitive methods for the detection of these molecules. In this methods article, we will describe protocols for the detection of such extracellular RNA using sensitive detection technologies such as digital PCR. These protocols should be valuable to researchers interested in the role and contribution of extracellular RNA to tumor cell biology.

  18. Extracellular Molecules Involved in Cancer Cell Invasion

    Energy Technology Data Exchange (ETDEWEB)

    Stivarou, Theodora; Patsavoudi, Evangelia, E-mail: epatsavoudi@pasteur.gr [Department of Biochemistry, Hellenic Pasteur Institute, Athens 11521 (Greece); Technological Educational Institute of Athens, Egaleo, Athens 12210 (Greece)

    2015-01-26

    Nowadays it is perfectly clear that understanding and eradicating cancer cell invasion and metastasis represent the crucial, definitive points in cancer therapeutics. During the last two decades there has been a great interest in the understanding of the extracellular molecular mechanisms involved in cancer cell invasion. In this review, we highlight the findings concerning these processes, focusing in particular on extracellular molecules, including extracellular matrix proteins and their receptors, growth factors and their receptors, matrix metalloproteinases and extracellular chaperones. We report the molecular mechanisms underlying the important contribution of this pool of molecules to the complex, multi-step phenomenon of cancer cell invasion.

  19. Extracellular Molecules Involved in Cancer Cell Invasion

    Directory of Open Access Journals (Sweden)

    Theodora Stivarou

    2015-01-01

    Full Text Available Nowadays it is perfectly clear that understanding and eradicating cancer cell invasion and metastasis represent the crucial, definitive points in cancer therapeutics. During the last two decades there has been a great interest in the understanding of the extracellular molecular mechanisms involved in cancer cell invasion. In this review, we highlight the findings concerning these processes, focusing in particular on extracellular molecules, including extracellular matrix proteins and their receptors, growth factors and their receptors, matrix metalloproteinases and extracellular chaperones. We report the molecular mechanisms underlying the important contribution of this pool of molecules to the complex, multi-step phenomenon of cancer cell invasion.

  20. Product Integrals and Wilson loops

    CERN Document Server

    Karp, R L

    2001-01-01

    Using product integrals we review the unambiguous mathematical representation of Wilson line and Wilson loop operators, including their behavior under gauge transformations and the non-abelian Stokes theorem. Interesting consistency conditions among Wilson lines are also presented.

  1. Thermal fluctuations in loop cosmology

    CERN Document Server

    Magueijo, J; Magueijo, Joao; Singh, Parampreet

    2007-01-01

    Quantum gravitational effects in loop quantum cosmology lead to a resolution of the initial singularity and have the potential to solve the horizon problem and generate a quasi scale-invariant spectrum of density fluctuations. We consider loop modifications to the behavior of the inverse scale factor below a critical scale in closed models and assume a purely thermal origin for the fluctuations. We show that the no-go results for scale invariance in classical thermal models can be evaded even if we just consider modifications to the background (zeroth order) gravitational dynamics. Since a complete and systematic treatment of the perturbed Einstein equations in loop cosmology is still lacking, we simply parameterize their expected modifications. These change quantitatively, but not qualitatively, our conclusions. We thus urge the community to more fully work out this complex aspect of loop cosmology, since the full picture would not only fix the free parameters of the theory, but also provide a model for a no...

  2. Loop Quantum Cosmology Gravitational Baryogenesis

    CERN Document Server

    Odintsov, S D

    2016-01-01

    Loop Quantum Cosmology is an appealing quantum completion of classical cosmology, which brings along various theoretical features which in many cases offer remedy or modify various classical cosmology aspects. In this paper we address the gravitational baryogenesis mechanism in the context of Loop Quantum Cosmology. As we demonstrate, when Loop Quantum Cosmology effects are taken into account in the resulting Friedmann equations for a flat Friedmann-Robertson-Walker Universe, then even for a radiation dominated Universe, the predicted baryon-to-entropy ratio from the gravitational baryogenesis mechanism is non-zero, in contrast to the Einstein-Hilbert case, in which case the baryon-to-entropy ratio is zero. We also discuss various other cases apart from the radiation domination case, and we discuss how the baryon-to-entropy ratio is affected from the parameters of the quantum theory. In addition, we use illustrative exact solutions of Loop Quantum Cosmology and we investigate under which circumstances the bar...

  3. Continuous smearing of Wilson Loops

    CERN Document Server

    Lohmayer, Robert

    2011-01-01

    Continuum smearing was introduced in section 4.1 of JHEP03, 064 (2006) as a meaningful continuum analogue of the well known set of lattice techniques by the same name. Here we apply continuous smearing in continuous space-time to Wilson loops in order to clarify what it does in the context of field theory and also in the context of the loop calculus of the Makeenko-Migdal equation.

  4. The Projectile inside the Loop

    OpenAIRE

    Varieschi, Gabriele U.

    2005-01-01

    In this paper we describe an alternative use of the loop-the-loop apparatus, which can be used to study an interesting case of projectile motion. We also present an effective way to perform and analyze these experiments, by using video capture software together with a digital video camera. These experiments can be integrated into classroom demonstrations for general physics courses, or become part of laboratory activities.

  5. Introduction to Loop Quantum Gravity

    OpenAIRE

    Mercuri, Simone

    2010-01-01

    The questions I have been asked during the 5th International School on Field Theory and Gravitation, have compelled me to give an account of the premises that I consider important for a beginner's approach to Loop Quantum Gravity. After a description of some general arguments and an introduction to the canonical theory of gravity, I review the background independent approach to quantum gravity, giving only a brief survey of Loop Quantum Gravity.

  6. Bifurcations of nontwisted heteroclinic loop

    Institute of Scientific and Technical Information of China (English)

    田清平; 朱德明

    2000-01-01

    Bifurcations of nontwisted and fine heteroclinic loops are studied for higher dimensional systems. The existence and its associated existing regions are given for the 1-hom orbit and the 1-per orbit, respectively, and bifurcation surfaces of the two-fold periodic orbit are also obtained. At last, these bifurcation results are applied to the fine heteroclinic loop for the planar system, which leads to some new and interesting results.

  7. Agonist-regulated Cleavage of the Extracellular Domain of Parathyroid Hormone Receptor Type 1*

    Science.gov (United States)

    Klenk, Christoph; Schulz, Stefan; Calebiro, Davide; Lohse, Martin J.

    2010-01-01

    The receptor for parathyroid hormone (PTHR) is a main regulator of calcium homeostasis and bone maintenance. As a member of class B of G protein-coupled receptors, it harbors a large extracellular domain, which is required for ligand binding. Here, we demonstrate that the PTHR extracellular domain is cleaved by a protease belonging to the family of extracellular metalloproteinases. We show that the cleavage takes place in a region of the extracellular domain that belongs to an unstructured loop connecting the ligand-binding parts and that the N-terminal 10-kDa fragment is connected to the receptor core by a disulfide bond. Cleaved receptor revealed reduced protein stability compared with noncleaved receptor, suggesting degradation of the whole receptor. In the presence of the agonistic peptides PTH(1–34), PTH(1–14), or PTH(1–31), the processing of the PTHR extracellular domain was inhibited, and receptor protein levels were stabilized. A processed form of the PTHR was also detected in human kidney. These findings suggest a new model of PTHR processing and regulation of its stability. PMID:20080964

  8. Agonist-regulated cleavage of the extracellular domain of parathyroid hormone receptor type 1.

    Science.gov (United States)

    Klenk, Christoph; Schulz, Stefan; Calebiro, Davide; Lohse, Martin J

    2010-03-19

    The receptor for parathyroid hormone (PTHR) is a main regulator of calcium homeostasis and bone maintenance. As a member of class B of G protein-coupled receptors, it harbors a large extracellular domain, which is required for ligand binding. Here, we demonstrate that the PTHR extracellular domain is cleaved by a protease belonging to the family of extracellular metalloproteinases. We show that the cleavage takes place in a region of the extracellular domain that belongs to an unstructured loop connecting the ligand-binding parts and that the N-terminal 10-kDa fragment is connected to the receptor core by a disulfide bond. Cleaved receptor revealed reduced protein stability compared with noncleaved receptor, suggesting degradation of the whole receptor. In the presence of the agonistic peptides PTH(1-34), PTH(1-14), or PTH(1-31), the processing of the PTHR extracellular domain was inhibited, and receptor protein levels were stabilized. A processed form of the PTHR was also detected in human kidney. These findings suggest a new model of PTHR processing and regulation of its stability.

  9. Extracellular DNA in oral microbial biofilms.

    Science.gov (United States)

    Jakubovics, Nicholas S; Burgess, J Grant

    2015-07-01

    The extracellular matrix of microbial biofilms is critical for surface adhesion and nutrient homeostasis. Evidence is accumulating that extracellular DNA plays a number of important roles in biofilm integrity and formation on hard and soft tissues in the oral cavity. Here, we summarise recent developments in the field and consider the potential of targeting DNA for oral biofilm control.

  10. Bol loops of odd prime exponent

    CERN Document Server

    Foguel, Tuval

    2009-01-01

    Although any finite Bol loop of odd prime exponent is solvable, we show there exist such Bol loops with trivial center. We also construct finitely generated, infinite, simple Bruck loops of odd prime exponent for sufficiently large primes. This shows that the Burnside problem for Bruck loops has a negative answer.

  11. Classifying Finitely Generated Indecomposable RA Loops

    CERN Document Server

    Cornelissen, Mariana

    2012-01-01

    In 1995, E. Jespers, G. Leal and C. Polcino Milies classified all finite ring alternative loops (RA loops for short) which are not direct products of proper subloops. In this paper we extend this result to finitely generated RA loops and provide an explicit description of all such loops.

  12. Kalman Orbit Optimized Loop Tracking

    Science.gov (United States)

    Young, Lawrence E.; Meehan, Thomas K.

    2011-01-01

    Under certain conditions of low signal power and/or high noise, there is insufficient signal to noise ratio (SNR) to close tracking loops with individual signals on orbiting Global Navigation Satellite System (GNSS) receivers. In addition, the processing power available from flight computers is not great enough to implement a conventional ultra-tight coupling tracking loop. This work provides a method to track GNSS signals at very low SNR without the penalty of requiring very high processor throughput to calculate the loop parameters. The Kalman Orbit-Optimized Loop (KOOL) tracking approach constitutes a filter with a dynamic model and using the aggregate of information from all tracked GNSS signals to close the tracking loop for each signal. For applications where there is not a good dynamic model, such as very low orbits where atmospheric drag models may not be adequate to achieve the required accuracy, aiding from an IMU (inertial measurement unit) or other sensor will be added. The KOOL approach is based on research JPL has done to allow signal recovery from weak and scintillating signals observed during the use of GPS signals for limb sounding of the Earth s atmosphere. That approach uses the onboard PVT (position, velocity, time) solution to generate predictions for the range, range rate, and acceleration of the low-SNR signal. The low- SNR signal data are captured by a directed open loop. KOOL builds on the previous open loop tracking by including feedback and observable generation from the weak-signal channels so that the MSR receiver will continue to track and provide PVT, range, and Doppler data, even when all channels have low SNR.

  13. Study of the Open Loop and Closed Loop Oscillator Techniques

    Energy Technology Data Exchange (ETDEWEB)

    Imel, George R. [Idaho State Univ., Pocatello, ID (United States); Baker, Benjamin [Idaho National Lab. (INL), Idaho Falls, ID (United States); Riley, Tony [Knolls Atomic Power Lab. (KAPL), Schenectady, NY (United States); Langbehn, Adam [Puget Sound Naval Base, Bremerton, WA (United States); Aryal, Harishchandra [Idaho State Univ., Pocatello, ID (United States); Benzerga, M. Lamine [Idaho State Univ., Pocatello, ID (United States)

    2015-04-11

    This report presents the progress and completion of a five-year study undertaken at Idaho State University of the measurement of very small worth reactivity samples comparing open and closed loop oscillator techniques.The study conclusively demonstrated the equivalency of the two techniques with regard to uncertainties in reactivity values, i.e., limited by reactor noise. As those results are thoroughly documented in recent publications, in this report we will concentrate on the support work that was necessary. For example, we describe in some detail the construction and calibration of a pilot rod for the closed loop system. We discuss the campaign to measure the required reactor parameters necessary for inverse-kinetics. Finally, we briefly discuss the transfer of the open loop technique to other reactor systems.

  14. BPS Wilson Loops on S^2 at Higher Loops

    CERN Document Server

    Young, Donovan

    2008-01-01

    We consider supersymmetric Wilson loops of the variety constructed by Drukker, Giombi, Ricci, and Trancanelli, whose spatial contours lie on a two-sphere. Working to second order in the 't Hooft coupling in planar N=4 Supersymmetric Yang-Mills Theory (SYM), we compute the vacuum expectation value of a wavy-latitude and of a loop composed of two longitudes. We evaluate the resulting integrals numerically and find that the results are consistent with the zero-instanton sector calculation of Wilson loops in 2-d Yang-Mills on S^2 performed by Bassetto and Griguolo. We also consider the connected correlator of two distinct latitudes to third order in the 't Hooft coupling in planar N=4 SYM. We compare the result in the limit where the latitudes become coincident to a perturbative calculation in 2-d Yang-Mills on S^2 using a light-cone Wu-Mandelstam-Leibbrandt prescription. The two calculations produce differing results.

  15. Generalized loop space and TMDs

    Directory of Open Access Journals (Sweden)

    Mertens Tom

    2014-06-01

    Full Text Available The Standard Model describes the three (of four basic interactions known in Nature in terms of the quantum fields which are constituted by representations of special unitary gauge groups of symmetry. However, the physical observables do not always coincide with the fundamental degrees of freedom of the Standard Model. Therefore it can be useful to switch to the loop space representation of the gauge theory, where the variables are inherently gauge invariant but the degrees of freedom are absorbed in the path/loop dependence. Over-completeness of this space requires the introduction of an equivalence relation which is provided by Wilson loop functionals operating on piecewise regular paths. It is well known that certain Wilson loops show the same singularity structure as some Transverse Momentum Dependent PDFs (TMDs, which are not renormalizable by the common methods due to exactly this singularity structure. By introducing geometrical operators, like the area-derivative, we were able to derive an evolution equation for these Wilson loops and we hope to apply this method in the future to find some renormalization schemes for TMDs.

  16. Loop coupled resonator optical waveguides.

    Science.gov (United States)

    Song, Junfeng; Luo, Lian-Wee; Luo, Xianshu; Zhou, Haifeng; Tu, Xiaoguang; Jia, Lianxi; Fang, Qing; Lo, Guo-Qiang

    2014-10-06

    We propose a novel coupled resonator optical waveguide (CROW) structure that is made up of a waveguide loop. We theoretically investigate the forbidden band and conduction band conditions in an infinite periodic lattice. We also discuss the reflection- and transmission- spectra, group delay in finite periodic structures. Light has a larger group delay at the band edge in a periodic structure. The flat band pass filter and flat-top group delay can be realized in a non-periodic structure. Scattering matrix method is used to calculate the effects of waveguide loss on the optical characteristics of these structures. We also introduce a tunable coupling loop waveguide to compensate for the fabrication variations since the coupling coefficient of the directional coupler in the loop waveguide is a critical factor in determining the characteristics of a loop CROW. The loop CROW structure is suitable for a wide range of applications such as band pass filters, high Q microcavity, and optical buffers and so on.

  17. Vertically Polarized Omnidirectional Printed Slot Loop AntennaPrinted Slot Loop Antenna (invited)

    DEFF Research Database (Denmark)

    Kammersgaard, Nikolaj Peter Iversen; Kvist, Søren Helstrup; Thaysen, Jesper

    2015-01-01

    A novel verticall A novel vertically polarized dpolarize , omnidirection omnidirectional l , printed slot loop antenna h sprinted slot loop antenna has been designed, simulated, fabricated, and measured. The slot loop works as a magnetic loop. The loop is loaded with inductors to insure uniform...

  18. Extracellular DNA metabolism in Haloferax volcanii

    Directory of Open Access Journals (Sweden)

    Scott eChimileski

    2014-02-01

    Full Text Available Extracellular DNA is found in all environments and is a dynamic component of the micro-bial ecosystem. Microbial cells produce and interact with extracellular DNA through many endogenous mechanisms. Extracellular DNA is processed and internalized for use as genetic information and as a major source of macronutrients, and plays several key roles within prokaryotic biofilms. Hypersaline sites contain some of the highest extracellular DNA con-centrations measured in nature–a potential rich source of carbon, nitrogen and phosphorus for halophilic microorganisms. We conducted DNA growth studies for the halophilic archaeon Haloferax volcanii DS2 and show that this model Halobacteriales strain is capable of using exogenous double-stranded DNA as a nutrient. Further experiments with varying medium composition, DNA concentration and DNA types revealed that DNA is utilized primarily as a phosphorus source, that growth on DNA is concentration-dependent and that DNA isolated from different sources is metabolized selectively, with a bias against highly divergent methylated DNA sources. Additionally, fluorescence microscopy experiments showed that labeled DNA colocalized with Haloferax volcanii cells. The gene Hvo_1477 was also identified using a comparative genomic approach as a factor likely to be involved in extracellular DNA processing at the cell surface, and deletion of Hvo_1477 created an H. volcanii strain deficient in its ability to grow on extracellular DNA. Widespread distribution of Hvo_1477 homologs in archaea suggests metabolism of extracellular DNA may be of broad ecological and physiological relevance in this domain of life.

  19. El loco y el idiota.

    OpenAIRE

    Alfredo Fierro Bardají

    1982-01-01

    El loco y el idiota -denominados así, según el uso cotidiano y vulgar, inmisericordemente despectivo -sin duda alguna son las dos figuras paradigmáticas de enajenación de la razón, el uno por desarreglo, el otro por defecto. El loco es el trastornado en su razón, el que se ha hecho un desbarajuste con un poder anímico esencialmente orientado a crear orden, a producir ideas claras y distintas. El idiota es el deficiente en su razón, el que participa de ella en medida tan escasa que se queda en...

  20. Binding of N-methylscopolamine to the extracellular domain of muscarinic acetylcholine receptors

    Science.gov (United States)

    Jakubík, Jan; Randáková, Alena; Zimčík, Pavel; El-Fakahany, Esam E.; Doležal, Vladimír

    2017-01-01

    Interaction of orthosteric ligands with extracellular domain was described at several aminergic G protein-coupled receptors, including muscarinic acetylcholine receptors. The orthosteric antagonists quinuclidinyl benzilate (QNB) and N-methylscopolamine (NMS) bind to the binding pocket of the muscarinic acetylcholine receptor formed by transmembrane α-helices. We show that high concentrations of either QNB or NMS slow down dissociation of their radiolabeled species from all five subtypes of muscarinic acetylcholine receptors, suggesting allosteric binding. The affinity of NMS at the allosteric site is in the micromolar range for all receptor subtypes. Using molecular modelling of the M2 receptor we found that E172 and E175 in the second extracellular loop and N419 in the third extracellular loop are involved in allosteric binding of NMS. Mutation of these amino acids to alanine decreased affinity of NMS for the allosteric binding site confirming results of molecular modelling. The allosteric binding site of NMS overlaps with the binding site of some allosteric, ectopic and bitopic ligands. Understanding of interactions of NMS at the allosteric binding site is essential for correct analysis of binding and action of these ligands.

  1. All digital pulsewidth control loop

    Science.gov (United States)

    Huang, Hong-Yi; Jan, Shiun-Dian; Pu, Ruei-Iun

    2013-03-01

    This work presents an all-digital pulsewidth control loop (ADPWCL). The proposed system accepts a wide range of input duty cycles and performs a fast correction to the target output pulsewidth. An all-digital delay-locked loop (DLL) with fast locking time using a simplified time to digital converter and a new differential two-step delay element is proposed. The area of the delay element is much smaller than that in conventional designs, while having the same delay range. A test chip is verified in a 0.18-µm CMOS process. The measured duty cycle ranges from 4% to 98% with 7-bit resolution.

  2. Loop quantum cosmology: Recent progress

    Indian Academy of Sciences (India)

    Martin Bojowald

    2004-10-01

    Aspects of the full theory of loop quantum gravity can be studied in a simpler context by reducing to symmetric models like cosmological ones. This leads to several applications where loop effects play a significant role when one is sensitive to the quantum regime. As a consequence, the structure of and the approach to classical singularities are very different from general relativity. The quantum theory is free of singularities, and there are new phenomenological scenarios for the evolution of the very early universe such as inflation. We give an overview of the main effects, focussing on recent results obtained by different groups.

  3. Loop quantum geometry: a primer

    Energy Technology Data Exchange (ETDEWEB)

    Corichi, Alejandro [Instituto de Ciencias Nucleares, Universidad Nacional Autonoma de Mexico, A. Postal 70-543, Mexico D.F. 04510 (Mexico)

    2005-01-15

    This is the written version of a lecture given at the 'VI Mexican School of Gravitation and Mathematical Physics' (Nov 21-27, 2004, Playa del Carmen, Mexico), introducing the basics of Loop Quantum Geometry. The purpose of the written contribution is to provide a Primer version, that is, a first entry into Loop Quantum Gravity and to present at the same time a friendly guide to the existing pedagogical literature on the subject. This account is geared towards graduate students and non-experts interested in learning the basics of the subject.

  4. LISA Pathfinder: OPD loop characterisation

    Science.gov (United States)

    Born, Michael; LPF Collaboration

    2017-05-01

    The optical metrology system (OMS) of the LISA Pathfinder mission is measuring the distance between two free-floating test masses with unprecedented precision. One of the four OMS heterodyne interferometers reads out the phase difference between the reference and the measurement laser beam. This phase from the reference interferometer is common to all other longitudinal interferometer read outs and therefore subtracted. In addition, the phase is fed back via the digital optical pathlength difference (OPD) control loop to keep it close to zero. Here, we analyse the loop parameters and compare them to on-ground measurement results.

  5. Loop Quantum Geometry: A primer

    OpenAIRE

    Corichi, Alejandro

    2005-01-01

    This is the written version of a lecture given at the ``VI Mexican School of Gravitation and Mathematical Physics" (Nov 21-27, 2004, Playa del Carmen, Mexico), introducing the basics of Loop Quantum Geometry. The purpose of the written contribution is to provide a Primer version, that is, a first entry into Loop Quantum Gravity and to present at the same time a friendly guide to the existing pedagogical literature on the subject. This account is geared towards graduate students and non-expert...

  6. and extracellular laccase isoenzymes from Pleurotus ostreatus ...

    African Journals Online (AJOL)

    ZMG

    Colonia Vicentina, Delegación Iztapalapa, 09340 México D.F., México. ... In this study, extracellular laccase enzymes produced by Pleurotus ostreatus was identified in .... the intracellular forms), through the modified zymography method of.

  7. Alternative methods for characterization of extracellular vesicles

    Directory of Open Access Journals (Sweden)

    Fatemeh eMomen-Heravi

    2012-09-01

    Full Text Available Extracellular vesicles are nano-sized vesicles released by all cells in vitro as well as in vivo. Their role has been implicated mainly in cell-cell communication, but also in disease biomarkers and more recently in gene delivery. They represent a snapshot of the cell status at the moment of release and carry bioreactive macromolecules such as nucleic acids, proteins and lipids. A major limitation in this emerging new field is the availability/awareness of techniques to isolate and properly characterize Extracellular vesicles. The lack of gold standards makes comparing different studies very difficult and may potentially hinder some Extracellular vesicles -specific evidence. Characterization of Extracellular vesicles has also recently seen many advances with the use of Nanoparticle Tracking Analysis (NTA, flow cytometry, cryo-EM instruments and proteomic technologies. In this review, we discuss the latest developments in translational technologies involving characterization methods including the facts in their support and the challenges they face.

  8. Bacterial binding to extracellular proteins - in vitro adhesion

    DEFF Research Database (Denmark)

    Schou, C.; Fiehn, N.-E.

    1999-01-01

    Viridans streptococci, bacterial adherence, extracellular matrix proteins, surface receptors, endocarditis......Viridans streptococci, bacterial adherence, extracellular matrix proteins, surface receptors, endocarditis...

  9. Ponderomotive Acceleration in Coronal Loops

    Science.gov (United States)

    Dahlburg, R. B.; Laming, J. M.; Taylor, B. D.; Obenschain, K.

    2016-11-01

    Ponderomotive acceleration has been asserted to be a cause of the first ionization potential (FIP) effect, the well-known enhancement in abundance by a factor of 3-4 over photospheric values of elements in the solar corona with FIP less than about 10 eV. It is shown here by means of numerical simulations that ponderomotive acceleration occurs in solar coronal loops, with the appropriate magnitude and direction, as a “by-product” of coronal heating. The numerical simulations are performed with the HYPERION code, which solves the fully compressible three-dimensional magnetohydrodynamic equations including nonlinear thermal conduction and optically thin radiation. Numerical simulations of coronal loops with an axial magnetic field from 0.005 to 0.02 T and lengths from 25,000 to 75,000 km are presented. In the simulations the footpoints of the axial loop magnetic field are convected by random, large-scale motions. There is a continuous formation and dissipation of field-aligned current sheets, which act to heat the loop. As a consequence of coronal magnetic reconnection, small-scale, high-speed jets form. The familiar vortex quadrupoles form at reconnection sites. Between the magnetic footpoints and the corona the reconnection flow merges with the boundary flow. It is in this region that the ponderomotive acceleration occurs. Mirroring the character of the coronal reconnection, the ponderomotive acceleration is also found to be intermittent.

  10. Dirac Induction for loop groups

    NARCIS (Netherlands)

    Posthuma, H.

    2011-01-01

    Using a coset version of the cubic Dirac operators for affine Lie algebras, we give an algebraic construction of the Dirac induction homomorphism for loop group representations. With this, we prove a homogeneous generalization of the Weyl-Kac character formula and show compatibility with Dirac induc

  11. Five-loop massive tadpoles

    CERN Document Server

    Luthe, T

    2016-01-01

    We provide an update on a long-term project that aims at evaluating massive vacuum integrals at the five-loop frontier, with high precision and in various space-time dimensions. A number of applications are sketched, mainly concerning the determination of anomalous dimensions, for quantum field theories in four, three and two dimensions.

  12. Loop quantum gravity and observations

    CERN Document Server

    Barrau, A

    2014-01-01

    Quantum gravity has long been thought to be completely decoupled from experiments or observations. Although it is true that smoking guns are still missing, there are now serious hopes that quantum gravity phenomena might be tested. We review here some possible ways to observe loop quantum gravity effects either in the framework of cosmology or in astroparticle physics.

  13. The extracellular RNA complement of Escherichia coli.

    Science.gov (United States)

    Ghosal, Anubrata; Upadhyaya, Bimal Babu; Fritz, Joëlle V; Heintz-Buschart, Anna; Desai, Mahesh S; Yusuf, Dilmurat; Huang, David; Baumuratov, Aidos; Wang, Kai; Galas, David; Wilmes, Paul

    2015-01-21

    The secretion of biomolecules into the extracellular milieu is a common and well-conserved phenomenon in biology. In bacteria, secreted biomolecules are not only involved in intra-species communication but they also play roles in inter-kingdom exchanges and pathogenicity. To date, released products, such as small molecules, DNA, peptides, and proteins, have been well studied in bacteria. However, the bacterial extracellular RNA complement has so far not been comprehensively characterized. Here, we have analyzed, using a combination of physical characterization and high-throughput sequencing, the extracellular RNA complement of both outer membrane vesicle (OMV)-associated and OMV-free RNA of the enteric Gram-negative model bacterium Escherichia coli K-12 substrain MG1655 and have compared it to its intracellular RNA complement. Our results demonstrate that a large part of the extracellular RNA complement is in the size range between 15 and 40 nucleotides and is derived from specific intracellular RNAs. Furthermore, RNA is associated with OMVs and the relative abundances of RNA biotypes in the intracellular, OMV and OMV-free fractions are distinct. Apart from rRNA fragments, a significant portion of the extracellular RNA complement is composed of specific cleavage products of functionally important structural noncoding RNAs, including tRNAs, 4.5S RNA, 6S RNA, and tmRNA. In addition, the extracellular RNA pool includes RNA biotypes from cryptic prophages, intergenic, and coding regions, of which some are so far uncharacterised, for example, transcripts mapping to the fimA-fimL and ves-spy intergenic regions. Our study provides the first detailed characterization of the extracellular RNA complement of the enteric model bacterium E. coli. Analogous to findings in eukaryotes, our results suggest the selective export of specific RNA biotypes by E. coli, which in turn indicates a potential role for extracellular bacterial RNAs in intercellular communication. © 2015 The

  14. Transcriptome of extracellular vesicles released by hepatocytes.

    Directory of Open Access Journals (Sweden)

    Felix Royo

    Full Text Available The discovery that the cells communicate through emission of vesicles has opened new opportunities for better understanding of physiological and pathological mechanisms. This discovery also provides a novel source for non-invasive disease biomarker research. Our group has previously reported that hepatocytes release extracellular vesicles with protein content reflecting the cell-type of origin. Here, we show that the extracellular vesicles released by hepatocytes also carry RNA. We report the messenger RNA composition of extracellular vesicles released in two non-tumoral hepatic models: primary culture of rat hepatocytes and a progenitor cell line obtained from a mouse foetal liver. We describe different subpopulations of extracellular vesicles with different densities and protein and RNA content. We also show that the RNA cargo of extracellular vesicles released by primary hepatocytes can be transferred to rat liver stellate-like cells and promote their activation. Finally, we provide in vitro and in vivo evidence that liver-damaging drugs galactosamine, acetaminophen, and diclofenac modify the RNA content of these vesicles. To summarize, we show that the extracellular vesicles secreted by hepatocytes contain various RNAs. These vesicles, likely to be involved in the activation of stellate cells, might become a new source for non-invasive identification of the liver toxicity markers.

  15. High Tc superconducting small loop antenna

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Z.; Mehler, M.J.; Maclean, T.S.M.; Lancaster, M.J.; Gough, C.E. (Univ. of Birmingham (UK)); Alford, N. (I.C.I. Advanced Materials Div., Runcorn (UK))

    1989-12-01

    The improvement in the radiation efficiency of an electrically small loop antenna is analysed when it is fabricated from a superconductor, and experimental results for a liquid nitrogen cooled, ceramic superconducting loop at 450MHz are presented. (orig.).

  16. Crystal packing effects on protein loops.

    Science.gov (United States)

    Rapp, Chaya S; Pollack, Rena M

    2005-07-01

    The effects of crystal packing on protein loop structures are examined by (1) a comparison of loops in proteins that have been crystallized in alternate packing arrangements, and (2) theoretical prediction of loops both with and without the inclusion of the crystal environment. Results show that in a minority of cases, loop geometries are dependent on crystal packing effects. Explicit representation of the crystal environment in a loop prediction algorithm can be used to model these effects and to reconstruct the structures, and relative energies, of a loop in alternative packing environments. By comparing prediction results with and without the inclusion of the crystal environment, the loop prediction algorithm can further be used to identify cases in which a crystal structure does not represent the most stable state of a loop in solution. We anticipate that this capability has implications for structural biology.

  17. Modified Continuous Loop Technique for microvascular anastomosis

    Directory of Open Access Journals (Sweden)

    Kumar Pramod

    2001-01-01

    Full Text Available A modified method of continuous loop technique for microvascular anastomosis is described. The handling of loop is easier & even last suture is placed under vision. This makes the microvascular anastomosis easier and simpler.

  18. NMR mapping of RANTES surfaces interacting with CCR5 using linked extracellular domains.

    Science.gov (United States)

    Schnur, Einat; Kessler, Naama; Zherdev, Yuri; Noah, Eran; Scherf, Tali; Ding, Fa-Xiang; Rabinovich, Svetlana; Arshava, Boris; Kurbatska, Victoria; Leonciks, Ainars; Tsimanis, Alexander; Rosen, Osnat; Naider, Fred; Anglister, Jacob

    2013-05-01

    Chemokines constitute a large family of small proteins that regulate leukocyte trafficking to the site of inflammation by binding to specific cell-surface receptors belonging to the G-protein-coupled receptor (GPCR) superfamily. The interactions between N-terminal (Nt-) peptides of these GPCRs and chemokines have been studied extensively using NMR spectroscopy. However, because of the lower affinities of peptides representing the three extracellular loops (ECLs) of chemokine receptors to their respective chemokine ligands, information concerning these interactions is scarce. To overcome the low affinity of ECL peptides to chemokines, we linked two or three CC chemokine receptor 5 (CCR5) extracellular domains using either biosynthesis in Escherichia coli or chemical synthesis. Using such chimeras, CCR5 binding to RANTES was followed using (1)H-(15)N-HSQC spectra to monitor titration of the chemokine with peptides corresponding to the extracellular surface of the receptor. Nt-CCR5 and ECL2 were found to be the major contributors to CCR5 binding to RANTES, creating an almost closed ring around this protein by interacting with opposing faces of the chemokine. A RANTES positively charged surface involved in Nt-CCR5 binding resembles the positively charged surface in HIV-1 gp120 formed by the C4 and the base of the third variable loop of gp120 (V3). The opposing surface on RANTES, composed primarily of β2-β3 hairpin residues, binds ECL2 and was found to be analogous to a surface in the crown of the gp120 V3. The chemical and biosynthetic approaches for linking GPCR surface regions discussed herein should be widely applicable to the investigation of interactions of extracellular segments of chemokine receptors with their respective ligands.

  19. Resumming the POPE at One Loop

    CERN Document Server

    Lam, Ho Tat

    2016-01-01

    The Pentagon Operator Product Expansion represents polygonal Wilson loops in planar $\\mathcal{N}=4$ super Yang-Mills in terms of a series of flux tube excitations for finite coupling. We demonstrate how to re-sum this series at the one loop level for the hexagonal Wilson loop dual to the six-point MHV amplitude. By summing over a series of effective excitations we find expressions which integrate to logarithms and polylogarithms, reproducing the known one-loop result.

  20. Loop Equations in Abelian Gauge Theories

    CERN Document Server

    Di Bartolo, C; Pe~na, F; Bartolo, Cayetano Di; Leal, Lorenzo; Peña, Francisco

    2005-01-01

    The equations obeyed by the vacuum expectation value of the Wilson loop of Abelian gauge theories are considered from the point of view of the loop-space. An approximative scheme for studying these loop-equations for lattice Maxwell theory is presented. The approximation leads to a partial difference equation in the area and length variables of the loop, and certain physically motivated ansatz is seen to reproduce the mean field results from a geometrical perspective.

  1. Estimation of complex permittivity using loop antenna

    DEFF Research Database (Denmark)

    Lenler-Eriksen, Hans-Rudolph; Meincke, Peter

    2004-01-01

    A method for estimating the complex permittivity of materials in the vicinity of a loop antenna is proposed. The method is based on comparing measured and numerically calculated input admittances for the loop antenna.......A method for estimating the complex permittivity of materials in the vicinity of a loop antenna is proposed. The method is based on comparing measured and numerically calculated input admittances for the loop antenna....

  2. Estimation of complex permittivity using loop antenna

    DEFF Research Database (Denmark)

    Lenler-Eriksen, Hans-Rudolph; Meincke, Peter

    2004-01-01

    A method for estimating the complex permittivity of materials in the vicinity of a loop antenna is proposed. The method is based on comparing measured and numerically calculated input admittances for the loop antenna.......A method for estimating the complex permittivity of materials in the vicinity of a loop antenna is proposed. The method is based on comparing measured and numerically calculated input admittances for the loop antenna....

  3. Polyhedra in loop quantum gravity

    CERN Document Server

    Bianchi, Eugenio; Speziale, Simone

    2010-01-01

    Interwiners are the building blocks of spin-network states. The space of intertwiners is the quantization of a classical symplectic manifold introduced by Kapovich and Millson. Here we show that a theorem by Minkowski allows us to interpret generic configurations in this space as bounded convex polyhedra in Euclidean space: a polyhedron is uniquely described by the areas and normals to its faces. We provide a reconstruction of the geometry of the polyhedron: we give formulas for the edge lengths, the volume and the adjacency of its faces. At the quantum level, this correspondence allows us to identify an intertwiner with the state of a quantum polyhedron, thus generalizing the notion of quantum tetrahedron familiar in the loop quantum gravity literature. Moreover, coherent intertwiners result to be peaked on the classical geometry of a polyhedron. We discuss the relevance of this result for loop quantum gravity. In particular, coherent spin-network states with nodes of arbitrary valence represent a collection...

  4. Nucleosome repositioning via loop formation

    CERN Document Server

    Kulic, M L

    2002-01-01

    Active (catalysed) and passive (intrinsic) nucleosome repositioning is known to be a crucial event during the transcriptional activation of certain eucaryotic genes. Here we consider theoretically the intrinsic mechanism and study in detail the energetics and dynamics of DNA-loop-mediated nucleosome repositioning, as previously proposed by Schiessel et al. (H. Schiessel, J. Widom, R. F. Bruinsma, and W. M. Gelbart. 2001. {\\it Phys. Rev. Lett.} 86:4414-4417). The surprising outcome of the present study is the inherent nonlocality of nucleosome motion within this model -- being a direct physical consequence of the loop mechanism. On long enough DNA templates the longer jumps dominate over the previously predicted local motion, a fact that contrasts simple diffusive mechanisms considered before. The possible experimental outcome resulting from the considered mechanism is predicted, discussed and compared to existing experimental findings.

  5. The Statistical Loop Analyzer (SLA)

    Science.gov (United States)

    Lindsey, W. C.

    1985-01-01

    The statistical loop analyzer (SLA) is designed to automatically measure the acquisition, tracking and frequency stability performance characteristics of symbol synchronizers, code synchronizers, carrier tracking loops, and coherent transponders. Automated phase lock and system level tests can also be made using the SLA. Standard baseband, carrier and spread spectrum modulation techniques can be accomodated. Through the SLA's phase error jitter and cycle slip measurements the acquisition and tracking thresholds of the unit under test are determined; any false phase and frequency lock events are statistically analyzed and reported in the SLA output in probabilistic terms. Automated signal drop out tests can be performed in order to trouble shoot algorithms and evaluate the reacquisition statistics of the unit under test. Cycle slip rates and cycle slip probabilities can be measured using the SLA. These measurements, combined with bit error probability measurements, are all that are needed to fully characterize the acquisition and tracking performance of a digital communication system.

  6. Loop Diuretics in Clinical Practice.

    Science.gov (United States)

    Oh, Se Won; Han, Sang Youb

    2015-06-01

    Diuretics are commonly used to control edema across various clinical fields. Diuretics inhibit sodium reabsorption in specific renal tubules, resulting in increased urinary sodium and water excretion. Loop diuretics are the most potent diuretics. In this article, we review five important aspects of loop diuretics, in particular furosemide, which must be considered when prescribing this medicine: (1) oral versus intravenous treatment, (2) dosage, (3) continuous versus bolus infusion, (4) application in chronic kidney disease patients, and (5) side effects. The bioavailability of furosemide differs between oral and intravenous therapy. Additionally, the threshold and ceiling doses of furosemide differ according to the particular clinical condition of the patient, for example in patients with severe edema or chronic kidney disease. To maximize the efficiency of furosemide, a clear understanding of how the mode of delivery will impact bioavailability and the required dosage is necessary.

  7. Deconfinement and virtual quark loops

    Science.gov (United States)

    Çelik, T.; Engels, J.; Satz, H.

    1983-12-01

    We calculate paer Monte Carlo evaluation on an 83 × 3 lattice the energy density ɛG of the gluon sector of QCD, including virtual quark loops up to the fourth power in the hopping parameter expansion. For light quarks of one flavour, we observe at T/ΛL 95 +/- 10 a rapid variation of ɛG in T, accompanied by strong fluctuations from iteration to iteration. as clear signal of the deconfinement transition.

  8. Quantum Reduced Loop Gravity and the foundation of Loop Quantum Cosmology

    CERN Document Server

    Alesci, Emanuele

    2016-01-01

    Quantum Reduced Loop Gravity is a promising framework for linking Loop Quantum Gravity and the effective semiclassical dynamics of Loop Quantum Cosmology. We review its basic achievements and its main perspectives, outlining how it provides a quantum description of the Universe in terms of a cuboidal graph which constitutes the proper framework for applying loop techniques in a cosmological setting.

  9. Vertebrate extracellular preovulatory and postovulatory egg coats.

    Science.gov (United States)

    Menkhorst, Ellen; Selwood, Lynne

    2008-11-01

    Extracellular egg coats deposited by maternal or embryonic tissues surround all vertebrate conceptuses during early development. In oviparous species, the time of hatching from extracellular coats can be considered equivalent to the time of birth in viviparous species. Extracellular coats must be lost during gestation for implantation and placentation to occur in some viviparous species. In the most recent classification of vertebrate extracellular coats, Boyd and Hamilton (Cleavage, early development and implantation of the egg. In: Parkes AS (ed.), Marshall's Physiology of Reproduction, vol. 2, 3rd ed. London: Longmans, Green & Co; 1961:1-126) defined the coat synthesized by the oocyte during oogenesis as primary and the coat deposited by follicle cells surrounding the oocyte as secondary. Tertiary egg coats are those synthesized and deposited around the primary or secondary coat by the maternal reproductive tract. This classification is difficult to reconcile with recent data collected using modern molecular biological techniques that can accurately establish the site of coat precursor synthesis and secretion. We propose that a modification to the classification by Boyd and Hamilton is required. Vertebrate egg coats should be classed as belonging to the following two broad groups: the preovulatory coat, which is deposited during oogenesis by the oocyte or follicle cells, and the postovulatory coats, which are deposited after fertilization by the reproductive tract or conceptus. This review discusses the origin and classification of vertebrate extracellular preovulatory and postovulatory coats and illustrates what is known about coat homology between the vertebrate groups.

  10. Ponderomotive Acceleration in Coronal Loops

    CERN Document Server

    Dahlburg, R B; Taylor, B D; Obenschain, K

    2016-01-01

    Ponderomotive acceleration has been asserted to be a cause of the First Ionization Potential (FIP) effect, the by now well known enhancement in abundance by a factor of 3-4 over photospheric values of elements in the solar corona with FIP less than about 10 eV. It is shown here by means of numerical simulations that ponderomotive acceleration occurs in solar coronal loops, with the appropriate magnitude and direction, as a "byproduct" of coronal heating. The numerical simulations are performed with the HYPERION code, which solves the fully compressible three-dimensional magnetohydrodynamic equations including nonlinear thermal conduction and optically thin radiation. Numerical simulations of a coronal loops with an axial magnetic field from 0.005 Teslas to 0.02 Teslas and lengths from 25000 km to 75000 km are presented. In the simulations the footpoints of the axial loop magnetic field are convected by random, large-scale motions. There is a continuous formation and dissipation of field-aligned current sheets...

  11. El agua y el arte

    OpenAIRE

    1999-01-01

    Not available.En el artículo «El agua y el arte» se analiza la importancia que tiene el agua en el mundo del arte, a través de los jardines y sus muchas variedades. El autor se refiere luego a los diversos aspectos que tienen el jardín francés, el jardín inglés, y el jardín español, de acuerdo con su geografía, pluviometría y cultura propias. El jardín español de abolengo musulmán es el jardín de los países secos que atesoran el agua como bien precioso, porque no lo regala la natu...

  12. El agua, el TLC y el agro

    Directory of Open Access Journals (Sweden)

    Alfredo Suárez Mejía

    2006-01-01

    Full Text Available Este artículo de absoluta actualidad se re- fiere al tratamiento que el poder ejecutivo viene dando al tema del agro y los recursos de los cuales depende. Ya en prensa el tema de tierras, corrupción y violencia ha sido registrado en relación con el gobierno del presidente Uribe y el Incoder. Ahora se trata de examinar de qué manera el Incoder desmonta el manejo y propiedad de los distritos de adecuación de tierras de los cuales depende la actividad agropecuaria sin que para tal expropiación del recurso agua se requiera acudir a las instancias de un TLC. La hipertrofia de las posiciones contra el TLC ha permitido sin lugar a dudas que desde el derecho interno mientras se negocia se adelanten las normas que permiten las inversiones que interesan al espacio de la “integración comercial”

  13. Modeling extracellular field potentials and the frequency-filtering properties of extracellular space

    CERN Document Server

    Bedard, C; Destexhe, A; Bédard, Claude; Kroeger, Helmut; Destexhe, Alain

    2003-01-01

    Extracellular local field potentials (LFP) are usually modeled as arising from a set of current sources embedded in a homogeneous extracellular medium. Although this formalism can successfully model several properties of LFPs, it does not account for their frequency-dependent attenuation with distance, a property essential to correctly model extracellular spikes. Here we derive expressions for the extracellular potential that include this frequency-dependent attenuation. We first show that, if the extracellular conductivity is non-homogeneous, there is induction of non-homogeneous charge densities which may result in a low-pass filter. We next derive a simplified model consisting of a punctual (or spherical) current source with spherically-symmetric conductivity/permittivity gradients around the source. We analyze the effect of different radial profiles of conductivity and permittivity on the frequency-filtering behavior of this model. We show that this simple model generally displays low-pass filtering behav...

  14. Modeling Phase-Locked Loops Using Verilog

    Science.gov (United States)

    2007-11-01

    a charge pump, the phase detector has a tri-state output that can drive a opamp loop filter directly. This signal is conditioned by the charge pump...then it can directly drive an opamp based loop filter. Most loop filters are based upon an integrator loop. The integrator loop filter is advantageous...replaced with an accumulator. The opamp circuit can be replaced by a digital filter using Z-transform theory z=exp(jwT), where T is the sampling

  15. Extracellular proteolysis in the adult murine brain.

    Science.gov (United States)

    Sappino, A P; Madani, R; Huarte, J; Belin, D; Kiss, J Z; Wohlwend, A; Vassalli, J D

    1993-08-01

    Plasminogen activators are important mediators of extracellular metabolism. In the nervous system, plasminogen activators are thought to be involved in the remodeling events required for cell migration during development and regeneration. We have now explored the expression of the plasminogen activator/plasmin system in the adult murine central nervous system. Tissue-type plasminogen activator is synthesized by neurons of most brain regions, while prominent tissue-type plasminogen activator-catalyzed proteolysis is restricted to discrete areas, in particular within the hippocampus and hypothalamus. Our observations indicate that tissue-type plasminogen activator-catalyzed proteolysis in neural tissues is not limited to ontogeny, but may also contribute to adult central nervous system physiology, for instance by influencing neuronal plasticity and synaptic reorganization. The identification of an extracellular proteolytic system active in the adult central nervous system may also help gain insights into the pathogeny of neurodegenerative disorders associated with extracellular protein deposition.

  16. The space of states of quantum gravity in terms of loops and extended loops some remarks

    CERN Document Server

    Di Bartolo, C; Griego, J R; Pullin, J; Di Bartolo, Cayetano; Gambini, Rodolfo; Griego, Jorge; Pullin, Jorge

    1995-01-01

    This article reviews the status of several solutions to all the constraints of quantum gravity that have been proposed in terms of loops and extended loops. We discuss pitfalls of several of the results and in particular discuss the issues of covariance and regularization of the constraints in terms of extended loops. We also propose a formalism for ``thickened out loops'' which does not face the covariance problems of extended loops and may allow to regularize expressions in a consistent manner.

  17. Hyperstaticity and loops in frictional granular packings

    Science.gov (United States)

    Tordesillas, Antoinette; Lam, Edward; Metzger, Philip T.

    2009-06-01

    The hyperstatic nature of granular packings of perfectly rigid disks is analyzed algebraically and through numerical simulation. The elementary loops of grains emerge as a fundamental element in addressing hyperstaticity. Loops consisting of an odd number of grains behave differently than those with an even number. For odd loops, the latent stresses are exterior and are characterized by the sum of frictional forces around each loop. For even loops, the latent stresses are interior and are characterized by the alternating sum of frictional forces around each loop. The statistics of these two types of loop sums are found to be Gibbsian with a "temperature" that is linear with the friction coefficient μ when μ<1.

  18. The extended loop representation of quantum gravity

    CERN Document Server

    Di Bartolo, C; Griego, J R

    1995-01-01

    A new representation of Quantum Gravity is developed. This formulation is based on an extension of the group of loops. The enlarged group, that we call the Extended Loop Group, behaves locally as an infinite dimensional Lie group. Quantum Gravity can be realized on the state space of extended loop dependent wavefunctions. The extended representation generalizes the loop representation and contains this representation as a particular case. The resulting diffeomorphism and hamiltonian constraints take a very simple form and allow to apply functional methods and simplify the loop calculus. In particular we show that the constraints are linear in the momenta. The nondegenerate solutions known in the loop representation are also solutions of the constraints in the new representation. The practical calculation advantages allows to find a new solution to the Wheeler-DeWitt equation. Moreover, the extended representation puts in a precise framework some of the regularization problems of the loop representation. We sh...

  19. El rey

    OpenAIRE

    Espitia, Juan Diego

    2014-01-01

    Murió el Rey. El sábado de este 2005 del tiempo. Murió el día sagrado de los hebreos. Aquellos pioneros fundamentales de su imperio. Que inventaron en el mundo o humo de los sueños el eje pos-terreno de la unidad. Dios solo. Único. Eterno

  20. Singularities in loop quantum cosmology.

    Science.gov (United States)

    Cailleteau, Thomas; Cardoso, Antonio; Vandersloot, Kevin; Wands, David

    2008-12-19

    We show that simple scalar field models can give rise to curvature singularities in the effective Friedmann dynamics of loop quantum cosmology (LQC). We find singular solutions for spatially flat Friedmann-Robertson-Walker cosmologies with a canonical scalar field and a negative exponential potential, or with a phantom scalar field and a positive potential. While LQC avoids big bang or big rip type singularities, we find sudden singularities where the Hubble rate is bounded, but the Ricci curvature scalar diverges. We conclude that the effective equations of LQC are not in themselves sufficient to avoid the occurrence of curvature singularities.

  1. Loop equations from differential systems

    CERN Document Server

    Eynard, Bertrand; Marchal, Olivier

    2016-01-01

    To any differential system $d\\Psi=\\Phi\\Psi$ where $\\Psi$ belongs to a Lie group (a fiber of a principal bundle) and $\\Phi$ is a Lie algebra $\\mathfrak g$ valued 1-form on a Riemann surface $\\Sigma$, is associated an infinite sequence of "correlators" $W_n$ that are symmetric $n$-forms on $\\Sigma^n$. The goal of this article is to prove that these correlators always satisfy "loop equations", the same equations satisfied by correlation functions in random matrix models, or the same equations as Virasoro or W-algebra constraints in CFT.

  2. Cygnus Loop: A double bubble?

    CERN Document Server

    West, J; Reichardt, I; Stil, J; Kothes, R; Jaffe, T

    2016-01-01

    The Cygnus Loop is a well-studied supernova remnant (SNR) that has been observed across the electromagnetic spectrum. Although widely believed to be an SNR shell with a blow- out region in the south, we consider the possibility that this object is two SNRs projected along the same line-of-sight by using multi-wavelength images and modelling. Our results show that a model of two objects including some overlap region/interaction between the two objects has the best match to the observed data.

  3. Closed-loop neuromorphic benchmarks

    CSIR Research Space (South Africa)

    Stewart

    2015-11-01

    Full Text Available Benchmarks   Terrence C. Stewart 1* , Travis DeWolf 1 , Ashley Kleinhans 2 , Chris Eliasmith 1   1 University of Waterloo, Canada, 2 Council for Scientific and Industrial Research, South Africa   Submitted to Journal:   Frontiers in Neuroscience   Specialty... the study was exempt from ethical approval procedures.) Did the study presented in the manuscript involve human or animal subjects: No I v i w 1Closed-loop Neuromorphic Benchmarks Terrence C. Stewart 1,∗, Travis DeWolf 1, Ashley Kleinhans 2 and Chris...

  4. Loop Virasoro Lie conformal algebra

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Henan, E-mail: wuhenanby@163.com; Chen, Qiufan; Yue, Xiaoqing [Department of Mathematics, Tongji University, Shanghai 200092 (China)

    2014-01-15

    The Lie conformal algebra of loop Virasoro algebra, denoted by CW, is introduced in this paper. Explicitly, CW is a Lie conformal algebra with C[∂]-basis (L{sub i} | i∈Z) and λ-brackets [L{sub i} {sub λ} L{sub j}] = (−∂−2λ)L{sub i+j}. Then conformal derivations of CW are determined. Finally, rank one conformal modules and Z-graded free intermediate series modules over CW are classified.

  5. El agua y el arte

    Directory of Open Access Journals (Sweden)

    Chueca Goitia, Fernando

    1999-10-01

    Full Text Available Not available.En el artículo «El agua y el arte» se analiza la importancia que tiene el agua en el mundo del arte, a través de los jardines y sus muchas variedades. El autor se refiere luego a los diversos aspectos que tienen el jardín francés, el jardín inglés, y el jardín español, de acuerdo con su geografía, pluviometría y cultura propias. El jardín español de abolengo musulmán es el jardín de los países secos que atesoran el agua como bien precioso, porque no lo regala la naturaleza y es necesario transportarlo y encerrarlo en el cofre de una arquitectura sugerente. Por eso el jardín español es un jardín recoleto y misterioso, enclaustrado y secreto, sin lejanías ni perspectivas. Se extiende luego el autor en los jardines de la Alhambra granadina, sin olvidar otros, principalmente andaluces. Jardines de los claustros monacales, de El Escorial y de los Sitios reales, también interesan, en suma, al articulista.

  6. Using the Meeting Graph Framework to Minimise Kernel Loop Unrolling for Scheduled Loops

    Science.gov (United States)

    Bachir, Mounira; Gregg, David; Touati, Sid-Ahmed-Ali

    This paper improves our previous research effort [1] by providing an efficient method for kernel loop unrolling minimisation in the case of already scheduled loops, where circular lifetime intervals are known. When loops are software pipelined, the number of values simultaneously alive becomes exactly known giving better opportunities for kernel loop unrolling. Furthermore, fixing circular lifetime intervals allows us to reduce the algorithmic complexity of our method compared to [1] by computing a new research space for minimal kernel loop unrolling. The meeting graph (MG) is one of the [3] frameworks proposed in the literature which models loop unrolling and register allocation together in a common formal framework for software pipelined loops. Although MG significantly improves loop register allocation, the computed loop unrolling may lead to unpractical code growth.

  7. Extracellular matrix and tissue engineering applications

    NARCIS (Netherlands)

    Fernandes, Hugo; Moroni, Lorenzo; Blitterswijk, van Clemens; Boer, de Jan

    2009-01-01

    The extracellular matrix is a key component during regeneration and maintenance of tissues and organs, and it therefore plays a critical role in successful tissue engineering as well. Tissue engineers should recognise that engineering technology can be deduced from natural repair processes. Due to a

  8. Extracellular vesicles: fundamentals and clinical relevance

    Directory of Open Access Journals (Sweden)

    Wael Nassar

    2015-01-01

    Full Text Available All types of cells of eukaryotic organisms produce and release small nanovesicles into their extracellular environment. Early studies have described these vesicles as ′garbage bags′ only to remove obsolete cellular molecules. Valadi and colleagues, in 2007, were the first to discover the capability of circulating extracellular vesicles (EVs to horizontally transfer functioning gene information between cells. These extracellular vesicles express components responsible for angiogenesis promotion, stromal remodeling, chemoresistance, genetic exchange, and signaling pathway activation through growth factor/receptor transfer. EVs represent an important mode of intercellular communication by serving as vehicles for transfer between cells of membrane and cytosolic proteins, lipids, signaling proteins, and RNAs. They contribute to physiology and pathology, and they have a myriad of potential clinical applications in health and disease. Moreover, vesicles can pass the blood-brain barrier and may perhaps even be considered as naturally occurring liposomes. These cell-derived EVs not only represent a central mediator of the disease microenvironment, but their presence in the peripheral circulation may serve as a surrogate for disease biopsies, enabling real-time diagnosis and disease monitoring. In this review, we′ll be addressing the characteristics of different types of extracellular EVs, as well as their clinical relevance and potential as diagnostic markers, and also define therapeutic options.

  9. Extracellular calmodulin: A polypeptide signal in plants?

    Institute of Scientific and Technical Information of China (English)

    孙大业; 唐文强; 马力耕

    2001-01-01

    Traditionally, calmodulin (CaM) was thought to be a multi-functional receptor for intracellular Ca2+ signals. But in the last ten years, it was found that CaM also exists and acts extracellularly in animal and plant cells to regulate many important physiological functions. Laboratory studies by the authors showed that extracellular CaM in plant cells can stimulate the proliferation of suspension cultured cell and protoplast; regulate pollen germination and pollen tube elongation,and stimulate the light-independent gene expression of Rubisco small subunit (rbcS). Furthermore,we defined the trans-membrane and intracellular signal transduction pathways for extracellular CaM by using a pollen system. The components in this pathway include heterotrimeric G-protein,phospholipase C, IP3, calcium signal and protein phosphorylation etc. Based on our findings, we suggest that extracellular CaM is a polypeptide signal in plants. This idea strongly argues against the traditional concept that there is no intercellular polypeptide signal in plants.

  10. Fragmentation of extracellular matrix by hypochlorous acid

    DEFF Research Database (Denmark)

    Woods, Alan A; Davies, Michael Jonathan

    2003-01-01

    The interaction of extracellular matrix with cells regulates their adhesion, migration and proliferation, and it is believed that damage to vascular matrix components is a factor in the development of atherosclerosis. Evidence has been provided for a role for the haem enzyme MPO (myeloperoxidase)...

  11. Are Coronal Loops Isothermal or Multithermal? Yes!

    CERN Document Server

    Schmelz, J T; Rightmire, L A; Kimble, J A; Del Zanna, G; Cirtain, J W; DeLuca, E E; Mason, H E

    2009-01-01

    Surprisingly few solar coronal loops have been observed simultaneously with TRACE and SOHO/CDS, and even fewer analyses of these loops have been conducted and published. The SOHO Joint Observing Program 146 was designed in part to provide the simultaneous observations required for in-depth temperature analysis of active region loops and determine whether these loops are isothermal or multithermal. The data analyzed in this paper were taken on 2003 January 17 of AR 10250. We used TRACE filter ratios, emission measure loci, and two methods of differential emission measure analysis to examine the temperature structure of three different loops. TRACE and CDS observations agree that Loop 1 is isothermal with Log T $=$ 5.85, both along the line of sight as well as along the length of the loop leg that is visible in the CDS field of view. Loop 2 is hotter than Loop 1. It is multithermal along the line of sight, with significant emission between 6.2 $<$ Log T $<$ 6.4, but the loop apex region is out of the CDS ...

  12. Gauge theory loop operators and Liouville theory

    Energy Technology Data Exchange (ETDEWEB)

    Drukker, Nadav [Humboldt Univ. Berlin (Germany). Inst. fuer Physik; Gomis, Jaume; Okuda, Takuda [Perimeter Inst. for Theoretical Physics, Waterloo, ON (Canada); Teschner, Joerg [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)

    2009-10-15

    We propose a correspondence between loop operators in a family of four dimensional N=2 gauge theories on S{sup 4} - including Wilson, 't Hooft and dyonic operators - and Liouville theory loop operators on a Riemann surface. This extends the beautiful relation between the partition function of these N=2 gauge theories and Liouville correlators found by Alday, Gaiotto and Tachikawa. We show that the computation of these Liouville correlators with the insertion of a Liouville loop operator reproduces Pestun's formula capturing the expectation value of a Wilson loop operator in the corresponding gauge theory. We prove that our definition of Liouville loop operators is invariant under modular transformations, which given our correspondence, implies the conjectured action of S-duality on the gauge theory loop operators. Our computations in Liouville theory make an explicit prediction for the exact expectation value of 't Hooft and dyonic loop operators in these N=2 gauge theories. The Liouville loop operators are also found to admit a simple geometric interpretation within quantum Teichmueller theory as the quantum operators representing the length of geodesics. We study the algebra of Liouville loop operators and show that it gives evidence for our proposal as well as providing definite predictions for the operator product expansion of loop operators in gauge theory. (orig.)

  13. Efficient Loop Navigation for Symbolic Execution

    CERN Document Server

    Obdrzalek, Jan

    2011-01-01

    Symbolic execution is a successful and very popular technique used in software verification and testing. A key limitation of symbolic execution is in dealing with code containing loops. The problem is that even a single loop can generate a huge number of different symbolic execution paths, corresponding to different number of loop iterations and taking various paths through the loop. We introduce a technique which, given a start location above some loops and a target location anywhere below these loops, returns a feasible path between these two locations, if such a path exists. The technique infers a collection of constraint systems from the program and uses them to steer the symbolic execution towards the target. On reaching a loop it iteratively solves the appropriate constraint system to find out which path through this loop to take, or, alternatively, whether to continue below the loop. To construct the constraint systems we express the values of variables modified in a loop as functions of the number of ...

  14. Structure and function of ameloblastin as an extracellular matrix protein: adhesion, calcium binding, and CD63 interaction in human and mouse.

    Science.gov (United States)

    Zhang, Xu; Diekwisch, Thomas G H; Luan, Xianghong

    2011-12-01

    The functional significance of extracellular matrix proteins in the life of vertebrates is underscored by a high level of sequence variability in tandem with a substantial degree of conservation in terms of cell-cell and cell-matrix adhesion interactions. Many extracellular matrix proteins feature multiple adhesion domains for successful attachment to substrates, such as integrin, CD63, and heparin. Here we have used homology and ab initio modeling algorithms to compare mouse ameloblastin (mAMBN) and human ameloblastin (hABMN) isoforms and to analyze their potential for cell adhesion and interaction with other matrix molecules as well as calcium binding. Sequence comparison between mAMBN and hAMBN revealed a 26-amino-acid deletion in mAMBN, corresponding to a helix-loop-helix frameshift. The human AMBN domain (174Q-201G), homologous to the mAMBN 157E-178I helix-loop-helix region, formed a helix-loop motif with an extended loop, suggesting a higher degree of flexibility of hAMBN compared with mAMBN, as confirmed by molecular dynamics simulation. Heparin-binding domains, CD63-interaction domains, and calcium-binding sites in both hAMBN and mAMBN support the concept of AMBN as an extracellular matrix protein. The high level of conservation between AMBN functional domains related to adhesion and differentiation was remarkable when compared with only 61% amino acid sequence homology.

  15. Extracellular calmodulin: A polypeptide signal in plants?

    Institute of Scientific and Technical Information of China (English)

    SUN; Daye(

    2001-01-01

    [1]Cheng. W. Y., Cyclic 3', 5'-nucleotide phosphodiestrase: demonstration of an activator, Biochm. Biophys. Res. Commun.,1970, 38: 533-538.[2]Boynton, A. L., Whitfield, J. F., MacManus, J. P., Calmodulin stimulates DNA synthesis by rat liver cells, BBRC.1980,95(2): 745-749.[3]Gorbacherskaya, L. V., Borovkova, T. V., Rybin, U. O. et al., Effect of exogenous calmodulin on lymphocyte proliferation in normal subjects, Bull Exp. Med. Biol., 1983, 95: 361-363.[4]Wong, P. Y.-K., Lee, W. H., Chao, PH.-W., The role of calmodulin in prostaglandin metabolism, Ann. NY Acad. Sci.,1980, 356: 179-189.[5]Mac Neil, S., Dawson, R. A., Crocker, G. et al., Effects of extracellular calmodulin and calmodulin antagonists on B16 melanoma cell growth, J. Invest. Dermatol., 1984, 83: 15-19.[6]Crocker, D. G., Dawson, R. A., Mac Neil, S. et al., An extracellular role for calmodulin-like activity in cell proliferation,Biochem. J., 1988, 253: 877-884.[7]Polito. V. S., Calmodulin and calmodulin inhibitors: effect on pollen germination and tube growth, in Pollen: Biology and Implications for Plant Breeding (eds. Mulvshy, D. L., Ottaviaro, E.), New York: Elsevier, 1983.53-60.[8]Biro, R. L., Sun, D. Y., Roux, S. J.et al., Characterization of oat calmodulin and radioimmunoassay of its subcellular distribution, Plant Physiol., 1984,75: 382-386.[9]Terry, M. E., Bonner, B. A., An examination of centrifugation as a method of extracting an extracellular solution from peas, and its use for the study of IAA-induced growth, Plant Physiol., 1980, 66: 321-325.[10]Josefina, H. N., Aldasars, J. J., Rodriguez, D., Localization of calmodulin on embryonic Cice aricium L, in Molecular and Cellular Aspects of Calcium in Plant Development (ed. Trewavas, A. J.), New York, London: Plenum Press, 1985, 313.[11]Dauwalder, M., Roux, S. J., Hardison, L., Distribution of calmodulin in pea seedling: immunocytochemical localization in plumules and root apices, Planta, 1986, 168: 461

  16. New insights into the structural bases of activation of Cys-loop receptors.

    Science.gov (United States)

    Bouzat, Cecilia

    2012-01-01

    Neurotransmitter receptors of the Cys-loop superfamily mediate rapid synaptic transmission throughout the nervous system, and include receptors activated by ACh, GABA, glycine and serotonin. They are involved in physiological processes, including learning and memory, and in neurological disorders, and they are targets for clinically relevant drugs. Cys-loop receptors assemble either from five copies of one type of subunit, giving rise to homomeric receptors, or from several types of subunits, giving rise to heteromeric receptors. Homomeric receptors are invaluable models for probing fundamental relationships between structure and function. Receptors contain a large extracellular domain that carries the binding sites and a transmembrane region that forms the ion pore. How the structural changes elicited by agonist binding are propagated through a distance of 50Å to the ion channel gate is central to understanding receptor function. Depending on the receptor subtype, occupancy of either two, as in the prototype muscle nicotinic receptor, or three binding sites, as in homomeric receptors, is required for full activation. The conformational changes initiated at the binding sites are propagated to the gate through the interface between the extracellular and transmembrane domains. This region forms a network that relays structural changes from the binding site towards the pore, and also contributes to open channel lifetime and rate of desensitization. Thus, this coupling region controls the beginning and duration of a synaptic response. Here we review recent advances in the molecular mechanism by which Cys-loop receptors are activated with particular emphasis on homomeric receptors.

  17. Oxidative and other posttranslational modifications in extracellular vesicle biology.

    Science.gov (United States)

    Szabó-Taylor, Katalin; Ryan, Brent; Osteikoetxea, Xabier; Szabó, Tamás G; Sódar, Barbara; Holub, Marcsilla; Németh, Andrea; Pálóczi, Krisztina; Pállinger, Éva; Winyard, Paul; Buzás, Edit I

    2015-04-01

    Extracellular vesicles including exosomes, microvesicles and apoptotic vesicles, are phospholipid bilayer surrounded structures secreted by cells universally, in an evolutionarily conserved fashion. Posttranslational modifications such as oxidation, citrullination, phosphorylation and glycosylation play diverse roles in extracellular vesicle biology. Posttranslational modifications orchestrate the biogenesis of extracellular vesicles. The signals extracellular vesicles transmit between cells also often function via modulating posttranslational modifications of target molecules, given that extracellular vesicles are carriers of several active enzymes catalysing posttranslational modifications. Posttranslational modifications of extracellular vesicles can also contribute to disease pathology by e.g. amplifying inflammation, generating neoepitopes or carrying neoepitopes themselves.

  18. Higher Loop Nonplanar Anomalous Dimensions from Symmetry

    CERN Document Server

    Koch, Robert de Mello; Messamah, Ilies

    2013-01-01

    In this article we study the action of the one loop dilatation operator on operators with a classical dimension of order N. These operators belong to the su(2) sector and are constructed using two complex fields Y and Z. For these operators non-planar diagrams contribute already at the leading order in N and the planar and large N limits are distinct. The action of the one loop and the two loop dilatation operator reduces to a set of decoupled oscillators and factorizes into an action on the Z fields and an action on the Y fields. Direct computation has shown that the action on the Y fields is the same at one and two loops. In this article, using the su(2) symmetry algebra as well as structural features of field theory, we give compelling evidence that the factor in the dilatation operator that acts on the Ys is given by the one loop expression, at any loop order.

  19. El agua, el TLC y el agro

    Directory of Open Access Journals (Sweden)

    Claudia Sampedro Torres

    2006-11-01

    Full Text Available Este artículo de absoluta actualidad se refiere al tratamiento que el poder ejecutivo viene dando al tema del agro y los recursos de los cuales depende. Ya en prensa el tema de tierras, corrupción y violencia ha sido registrado en relación con el gobierno del presidente Uribe y el Incoder. Ahora se trata de examinar de qué manera el Incoder desmonta el manejo y propiedad de los distritos de adecuación de tierras de los cuales depende la actividad agropecuaria sin que para tal expropiación del recurso agua se requiera acudir a las instancias de un

  20. Abstract Acceleration of General Linear Loops

    OpenAIRE

    2014-01-01

    International audience; We present abstract acceleration techniques for computing loop invariants for numerical programs with linear assignments and conditionals. Whereas abstract interpretation techniques typically over-approximate the set of reachable states iteratively, abstract acceleration captures the effect of the loop with a single, non-iterative transfer function applied to the initial states at the loop head. In contrast to previous acceleration techniques, our approach applies to a...

  1. LMFBR with booster pump in pumping loop

    Science.gov (United States)

    Rubinstein, H.J.

    1975-10-14

    A loop coolant circulation system is described for a liquid metal fast breeder reactor (LMFBR) utilizing a low head, high specific speed booster pump in the hot leg of the coolant loop with the main pump located in the cold leg of the loop, thereby providing the advantages of operating the main pump in the hot leg with the reliability of cold leg pump operation.

  2. Wilson Loops in Open String Theory

    Science.gov (United States)

    Shiraishi, Kiyoshi

    Wilson loop elements on torus are introduced into the partition function of open strings as Polyakov’s path integral at one-loop level. Mass spectra from compactification and expected symmetry breaking are illustrated by choosing the correct weight for the contributions from annulus and Möbius strip. We show that Jacobi’s imaginary transformation connects the mass spectra with the Wilson loops. The application to thermopartition function and cosmological implications are briefly discussed.

  3. Wilson Loops in Open String Theory

    CERN Document Server

    Shiraishi, Kiyoshi

    2012-01-01

    Wilson loop elements on torus are introduced into the partition function of open strings as Polyakov's path integral at one-loop level. Mass spectra from compactification and expected symmetry breaking are illustrated by choosing the correct weight for the contributions from annulus and M\\"obius strip. We show that Jacobi's imaginary transformation connects the mass spectra with the Wilson loops. The application to thermopartition function and cosmological implications are briefly discussed.

  4. All Digital Phase-Locked Loop

    OpenAIRE

    Marijan Jurgo

    2013-01-01

    The paper reviews working principles of phase-locked loop and drawbacks of classical PLL structure in nanometric technologies. It is proposed to replace the classical structure by all-digital phase-locked loop structure. Authors described the main blocks of all-digital phase-locked loop (time to digital converter and digitally controlled oscillator) and overviewed the quantization noise arising in these blocks as well as its minimization strategies. The calculated inverter delay in 65 nm CMOS...

  5. Magnetic Monopole in the Loop Representation

    CERN Document Server

    Leal, L; Leal, Lorenzo; Lopez, Alexander

    2004-01-01

    We quantize the electromagnetic field in the presence of a static magnetic monopole, within the loop-representation formalism. We find that the loop-dependent wave functional becomes multivalued, in the sense that it acquires a dependence on the surfaces bounded by the loop. This generalizes what occurs in quantum mechanics in multiply connected spaces. When Dirac's quantization condition holds, this surface-dependence disappears, together with the effect of the monopole on the electromagnetic field.

  6. A Note on Loop Amplitudes in QED

    CERN Document Server

    Brandhuber, Andreas; Vincon, Massimiliano

    2009-01-01

    We consider the two-loop four-point amplitude in N=2 super QED, and show that there exists an approximate recursive structure similar to that captured by the ABDK/BDS ansatz for MHV amplitudes in N=4 super Yang-Mills. Furthermore, we present a simple relation between the box coefficients of one-loop photon MHV amplitudes in (super) QED, and sums of box coefficients of one-loop MHV amplitudes in (super) Yang-Mills.

  7. Human-in-the-loop simulations

    CERN Document Server

    Rothrock, Ling

    2011-01-01

    ""Human-in-the-Loop Simulations"" is a compilation of articles from experts in the design, development, and use of human-in-the-loop simulations. The first section of the handbook consists of papers on fundamental concepts in human-in-the-loop simulations, such as object-oriented simulation development, interface design and development, and performance measurement. The second section includes papers from researchers who utilized HITL simulations to inform models of cognitive processes to include decision making and metacognition. The last section describes human-in-the-loop processes for compl

  8. High Temperature Sodium Thermal Convection Test Loop

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    A project for the evaluation of compatibility characteristic of structural materials used in China experimental fast reactor(CEFR) has been in operation. The conditions which these structural materials contact with liquid sodium in reactor can be simulated by the tests in high temperature sodium thermal convection test loop. The main aims of designing and constructing the thermal convection test loop is for the corrosion test of CEFR materials, and the objective is to obtain the corrosion data of domestic materials.The main features of the test loop are shown in Fig.1. The primary components of the loop

  9. The emergy analysis of loop circuit.

    Science.gov (United States)

    Cao, Kai; Feng, Xiao

    2008-12-01

    Emergy analysis can analyze the resource utilization and environmental performance of a system. Loop circuit is a common structure in the process industry, but when emergy analysis is carried out to such structure, mistakes such as emergy double counting often occur. To avoid emergy double counting, two types of loop circuit-direct loop circuit and indirect loop circuit-are theoretically distinguished, and the methods to avoid such mistake are proposed. Finally, PVC production and vinyl acetate production are adopted to demonstrate the methods.

  10. Pseudoautomorphisms of Bruck loops and their generalizations

    CERN Document Server

    Greer, Mark

    2012-01-01

    We show that in a weak commutative inverse property loop, such as a Bruck loop, if $\\alpha$ is a right [left] pseudoautomorphism with companion $c$, then $c$ [$c^2$] must lie in the left nucleus. In particular, for any such loop with trivial left nucleus, every right pseudoautomorphism is an automorphism and if the squaring map is a permutation, then every left pseudoautomorphism is an automorphism as well. We also show that every pseudoautomorphism of a commutative inverse property loop is an automorphism, generalizing a well-known result of Bruck.

  11. On Bruck Loops of 2-power Exponent

    CERN Document Server

    Baumeister, Barbara; Stroth, Gernot

    2009-01-01

    We classify "nice" loop envelopes to Bruck loops of 2-power exponent under the assumption that every nonabelian simple section of $G$ is either passive or isomorphic to $\\PSL_2(q)$, $q-1 \\ge 4$ a 2-power. The hypothesis is verified in a separate paper. This paper is a continuation of the work by Aschbacher, Kinyon and Phillips on finite Bruck loops [AKP]. In [BS3] we applied these results and get a neat description of the structure of the finite Bruck loops.

  12. Loops with exponent three in all isotopes

    CERN Document Server

    Kinyon, Michael

    2011-01-01

    It was shown by van Rees \\cite{vR} that a latin square of order $n$ cannot have more than $n^2(n-1)/18$ latin subsquares of order 3. He conjectured that this bound is only achieved if $n$ is a power of 3. We show that it can only be achieved if $n\\equiv3\\bmod6$. We also state several conditions that are equivalent to achieving the van Rees bound. One of these is that the Cayley table of a loop achieves the van Rees bound if and only if every loop isotope has exponent 3. We call such loops \\emph{van Rees loops} and show that they form an equationally defined variety. We also show that (1) In a van Rees loop, any subloop of index 3 is normal, (2) There are exactly 6 nonassociative van Rees loops of order 27 with a non-trivial nucleus, (3) There is a Steiner quasigroup associated with every van Rees loop and (4) Every Bol loop of exponent 3 is a van Rees loop.

  13. Polyakov loop modeling for hot QCD

    Science.gov (United States)

    Fukushima, Kenji; Skokov, Vladimir

    2017-09-01

    We review theoretical aspects of quantum chromodynamics (QCD) at finite temperature. The most important physical variable to characterize hot QCD is the Polyakov loop, which is an approximate order parameter for quark deconfinement in a hot gluonic medium. Additionally to its role as an order parameter, the Polyakov loop has rich physical contents in both perturbative and non-perturbative sectors. This review covers a wide range of subjects associated with the Polyakov loop from topological defects in hot QCD to model building with coupling to the Polyakov loop.

  14. Vertically Polarized Omnidirectional Printed Slot Loop Antenna

    DEFF Research Database (Denmark)

    Kammersgaard, Nikolaj Peter Iversen; Kvist, Søren H.; Thaysen, Jesper

    2015-01-01

    A novel vertically polarized omnidirectional printed slot loop antenna has been designed, simulated, fabricated and measured. The slot loop works as a magnetic loop. The loop is loaded with inductors to insure uniform and in-phase fields in the slot in order to obtain an omnidirectional radiation...... pattern. The antenna is designed for the 2.45 GHz Industrial, Scientific and Medical band. Applications of the antenna are many. One is for on-body applications since it is ideal for launching a creeping waves due to the polarization....

  15. El Aí y El Bradipo

    Directory of Open Access Journals (Sweden)

    García Paredes Antonio

    1942-08-01

    Full Text Available El ai y el bradipo son conocidos en la ciencia y en los catálogos de historia natural con los nombres vulgares de perezosos y con el irónico de perico ligero, por sus movimientos lentos y trabajosos y por el modo de moverse en el suelo como los pericos. Estas dos especies de animales salvajes son exclusivamente de la fauna americana, y se las encuentra en reducido número en las selvas tropicales desde el sur de Méjico hasta la Argentina, en los climas ardientes.

  16. Involvement of extracellular matrix constituents in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lochter, Andre; Bissell, Mina J

    1995-06-01

    It has recently been established that the extracellular matrix is required for normal functional differentiation of mammary epithelia not only in culture, but also in vivo. The mechanisms by which extracellular matrix affects differentiation, as well as the nature of extracellular matrix constituents which have major impacts on mammary gland function, have only now begun to be dissected. The intricate variety of extracellular matrix-mediated events and the remarkable degree of plasticity of extracellular matrix structure and composition at virtually all times during ontogeny, make such studies difficult. Similarly, during carcinogenesis, the extracellular matrix undergoes gross alterations, the consequences of which are not yet precisely understood. Nevertheless, an increasing amount of data suggests that the extracellular matrix and extracellular matrix-receptors might participate in the control of most, if not all, of the successive stages of breast tumors, from appearance to progression and metastasis.

  17. R-loopDB: a database for R-loop forming sequences (RLFS) and R-loops

    Science.gov (United States)

    Jenjaroenpun, Piroon; Wongsurawat, Thidathip; Sutheeworapong, Sawannee; Kuznetsov, Vladimir A.

    2017-01-01

    R-loopDB (http://rloop.bii.a-star.edu.sg) was originally constructed as a collection of computationally predicted R-loop forming sequences (RLFSs) in the human genic regions. The renewed R-loopDB provides updates, improvements and new options, including access to recent experimental data. It includes genome-scale prediction of RLFSs for humans, six other animals and yeast. Using the extended quantitative model of RLFSs (QmRLFS), we significantly increased the number of RLFSs predicted in the human genes and identified RLFSs in other organism genomes. R-loopDB allows searching of RLFSs in the genes and in the 2 kb upstream and downstream flanking sequences of any gene. R-loopDB exploits the Ensembl gene annotation system, providing users with chromosome coordinates, sequences, gene and genomic data of the 1 565 795 RLFSs distributed in 121 056 genic or proximal gene regions of the covered organisms. It provides a comprehensive annotation of Ensembl RLFS-positive genes including 93 454 protein coding genes, 12 480 long non-coding RNA and 7 568 small non-coding RNA genes and 7 554 pseudogenes. Using new interface and genome viewers of R-loopDB, users can search the gene(s) in multiple species with keywords in a single query. R-loopDB provides tools to carry out comparative evolution and genome-scale analyses in R-loop biology. PMID:27899586

  18. UWB communication receiver feedback loop

    Science.gov (United States)

    Spiridon, Alex; Benzel, Dave; Dowla, Farid U.; Nekoogar, Faranak; Rosenbury, Erwin T.

    2007-12-04

    A novel technique and structure that maximizes the extraction of information from reference pulses for UWB-TR receivers is introduced. The scheme efficiently processes an incoming signal to suppress different types of UWB as well as non-UWB interference prior to signal detection. Such a method and system adds a feedback loop mechanism to enhance the signal-to-noise ratio of reference pulses in a conventional TR receiver. Moreover, sampling the second order statistical function such as, for example, the autocorrelation function (ACF) of the received signal and matching it to the ACF samples of the original pulses for each transmitted bit provides a more robust UWB communications method and system in the presence of channel distortions.

  19. Delay locked loop integrated circuit.

    Energy Technology Data Exchange (ETDEWEB)

    Brocato, Robert Wesley

    2007-10-01

    This report gives a description of the development of a Delay Locked Loop (DLL) integrated circuit (IC). The DLL was developed and tested as a stand-alone IC test chip to be integrated into a larger application specific integrated circuit (ASIC), the Quadrature Digital Waveform Synthesizer (QDWS). The purpose of the DLL is to provide a digitally programmable delay to enable synchronization between an internal system clock and external peripherals with unknown clock skew. The DLL was designed and fabricated in the IBM 8RF process, a 0.13 {micro}m CMOS process. It was designed to operate with a 300MHz clock and has been tested up to 500MHz.

  20. Wilson loops with arbitrary charges

    CERN Document Server

    Korcyl, Piotr; Wosiek, Jacek

    2014-01-01

    We discuss how to implement, in lattice gauge theories, external charges which are not commensurate with an elementary gauge coupling. It is shown that an arbitrary, real power of a standard Wilson loop (or Polyakov line) can be defined and consistently computed in lattice formulation of non-abelian, two dimensional gauge theories. However, such an observable can excite quantum states with integer fluxes only. Since the non-integer fluxes are not in the spectrum of the theory they cannot be created, no matter which observable is chosen. Also the continuum limit of above averages does not exist unless the powers in question are in fact integer. On the other hand, a new continuum limit exists, which is rather intuitive, and where above observables make perfect sense and lead to the string tension proportional to the square of arbitrary (non necessary commensurate with gauge coupling) charge.

  1. A Loop-philic Pseudoscalar

    CERN Document Server

    Li, Gang; Tang, Yi-Lei; Zhang, Chen; Zhou, Yang; Zhu, Shou-hua

    2015-01-01

    We construct a weakly-coupled renormalizable model to explain the 750 $\\mbox{GeV}$ diphoton excess. The 750 $\\mbox{GeV}$ resonance (denoted as $X(750)$) is interpreted as a pseudoscalar which comes from a complex singlet. The model also naturally provides a dark matter candidate. One most attractive feature of our model is that decays of $X(750)$ are all loop-induced so the diphoton rate is not diluted by unwanted tree level branching fractions. Relevant Yukawa interactions need not to be tuned to nearly non-perturbative region to explain the rate. The model is highly predictive, including the pseudoscalar nature of the new resonance, and two nearly mass-degenerate quarks carrying electric charge $5/3$ and $2/3$. In our model, rich phenomenology is expected with respect to collider searches, flavor physics and dark matter searches in various manners, if $X(750)$ can be pinned down by future LHC experiments.

  2. Inflation and Loop Quantum Cosmology

    CERN Document Server

    Barrau, Aurelien

    2010-01-01

    On the one hand, inflation is an extremely convincing scenario: it solves most cosmological paradoxes and generates fluctuations that became the seeds for the growth of structures. It, however, suffers from a "naturalness" problem: generating initial conditions for inflation is far from easy. On the other hand, loop quantum cosmology is very successful: it solves the Big Bang singularity through a non-perturbative and background-independent quantization of general relativity. It, however, suffers from a key drawback: it is extremely difficult to test. Recent results can let us hope that inflation and LQC could mutually cure those pathologies: LQC seems to naturally generate inflation and inflation could allow us to test LQC.

  3. Lectures on Loop Quantum Gravity

    CERN Document Server

    Thiemann, T

    2003-01-01

    Quantum General Relativity (QGR), sometimes called Loop Quantum Gravity, has matured over the past fifteen years to a mathematically rigorous candidate quantum field theory of the gravitational field. The features that distinguish it from other quantum gravity theories are 1) background independence and 2) minimality of structures. Background independence means that this is a non-perturbative approach in which one does not perturb around a given, distinguished, classical background metric, rather arbitrary fluctuations are allowed, thus precisely encoding the quantum version of Einstein's radical perception that gravity is geometry. Minimality here means that one explores the logical consequences of bringing together the two fundamental principles of modern physics, namely general covariance and quantum theory, without adding any experimentally unverified additional structures. The approach is purposely conservative in order to systematically derive which basic principles of physics have to be given up and mu...

  4. Lose Your Loops with Numpy

    CERN Document Server

    CERN. Geneva

    2016-01-01

    Developing in python is fast. Computation, however, can often be another story. Or at least that is how it may seem. When working with arrays and numerical datasets one can subvert many of python’s computational limitations by utilizing numpy. Numpy is python’s standard matrix computation library. Many python users only use numpy to store and generate arrays, failing to utilize one of python’s most powerful computational tools. By leveraging numpy’s ufuncs, aggregation, broadcasting and slicing/masking/indexing functionality one can cut back on slow python loops and increase the speed of their programs by as much as 100x. This talk aims at teaching attendees how to use these tools through toy examples.

  5. Extracellular matrix component signaling in cancer

    DEFF Research Database (Denmark)

    Multhaupt, Hinke A. B.; Leitinger, Birgit; Gullberg, Donald

    2016-01-01

    Cell responses to the extracellular matrix depend on specific signaling events. These are important from early development, through differentiation and tissue homeostasis, immune surveillance, and disease pathogenesis. Signaling not only regulates cell adhesion cytoskeletal organization and motil...... as well as matrix constitution and protein crosslinking. Here we summarize roles of the three major matrix receptor types, with emphasis on how they function in tumor progression. [on SciFinder(R)]......Cell responses to the extracellular matrix depend on specific signaling events. These are important from early development, through differentiation and tissue homeostasis, immune surveillance, and disease pathogenesis. Signaling not only regulates cell adhesion cytoskeletal organization...... and motility but also provides survival and proliferation cues. The major classes of cell surface receptors for matrix macromols. are the integrins, discoidin domain receptors, and transmembrane proteoglycans such as syndecans and CD44. Cells respond not only to specific ligands, such as collagen, fibronectin...

  6. Biotechnological Aspects of Microbial Extracellular Electron Transfer

    Science.gov (United States)

    Kato, Souichiro

    2015-01-01

    Extracellular electron transfer (EET) is a type of microbial respiration that enables electron transfer between microbial cells and extracellular solid materials, including naturally-occurring metal compounds and artificial electrodes. Microorganisms harboring EET abilities have received considerable attention for their various biotechnological applications, in addition to their contribution to global energy and material cycles. In this review, current knowledge on microbial EET and its application to diverse biotechnologies, including the bioremediation of toxic metals, recovery of useful metals, biocorrosion, and microbial electrochemical systems (microbial fuel cells and microbial electrosynthesis), were introduced. Two potential biotechnologies based on microbial EET, namely the electrochemical control of microbial metabolism and electrochemical stimulation of microbial symbiotic reactions (electric syntrophy), were also discussed. PMID:26004795

  7. El factoring

    Directory of Open Access Journals (Sweden)

    Alberto Rosenthal

    1988-04-01

    Full Text Available RESUMEN El artículo  presenta, una conceptualización general de lo que es el factoring, el origen del mismo, su evolución y hace una clasificación de los distintos tipos de factoring.

  8. Exchange of extracellular domains of CCR1 and CCR5 reveals confined functions in CCL5-mediated cell recruitment.

    Science.gov (United States)

    Kramp, Birgit K; Megens, Remco T A; Sarabi, Alisina; Winkler, Sabine; Projahn, Delia; Weber, Christian; Koenen, Rory R; von Hundelshausen, Philipp

    2013-10-01

    The chemokine CCL5 recruits monocytes into inflamed tissues by triggering primarily CCR1-mediated arrest on endothelial cells, whereas subsequent spreading is dominated by CCR5. The CCL5-induced arrest can be enhanced by heteromer formation with CXCL4. To identify mechanisms for receptor-specific functions, we employed CCL5 mutants and transfectants expressing receptor chimeras carrying transposed extracellular regions. Mutation of the basic 50s cluster of CCL5, a coordinative site for CCL5 surface presentation, reduced CCR5- but not CCR1-mediated arrest and transmigration. Impaired arrest was restored by exchanging the CCR5-N-terminus for that of CCR1, which supported arrest even without the 50s cluster, whereas mutation of the basic 40s cluster essential for proteoglycan binding of CCL5 could not be rescued. The enhancement of CCL5-induced arrest by CXCL4 was mediated by CCR1 requiring its third extracellular loop. The domain exchanges did not affect formation and co-localisation of receptor dimers, indicating a sensing role of the third extracellular loop for hetero-oligomers in an arrest microenvironment. Our data identify confined targetable regions of CCR1 specialised to facilitate CCL5-induced arrest and enhanced responsiveness to the CXCL4-CCL5 heteromer.

  9. Tetraspanins in Extracellular Vesicle Formation and Function

    OpenAIRE

    Andreu, Zoraida; Yáñez-Mó, María

    2014-01-01

    Extracellular vesicles (EVs) represent a novel mechanism of intercellular communication as vehicles for intercellular transfer of functional membrane and cytosolic proteins, lipids, and RNAs. Microvesicles, ectosomes, shedding vesicles, microparticles, and exosomes are the most common terms to refer to the different kinds of EVs based on their origin, composition, size, and density. Exosomes have an endosomal origin and are released by many different cell types, participating in different phy...

  10. Tetraspanins in Extracellular Vesicle formation and function

    OpenAIRE

    Zoraida Andreu Martínez; María eYáñez-Mó

    2014-01-01

    Extracellular vesicles (EVs) represent a novel mechanism of intercellular communication as vehicles for intercellular transfer of functional membrane and cytosolic proteins, lipids, and RNAs. Microvesicles, ectosomes, shedding vesicles, microparticles and exosomes are the most common terms to refer to the different kinds of EVs based on their origin, composition, size and density. Exosomes have an endosomal origin and are released by many different cell types, participating in different physi...

  11. Engineering hydrogels as extracellular matrix mimics

    OpenAIRE

    Geckil, Hikmet; Xu, Feng; Zhang, Xiaohui; Moon, SangJun; Demirci, Utkan

    2010-01-01

    Extracellular matrix (ECM) is a complex cellular environment consisting of proteins, proteoglycans, and other soluble molecules. ECM provides structural support to mammalian cells and a regulatory milieu with a variety of important cell functions, including assembling cells into various tissues and organs, regulating growth and cell–cell communication. Developing a tailored in vitro cell culture environment that mimics the intricate and organized nanoscale meshwork of native ECM is desirable....

  12. On the Properties of Cosmic String Loops

    Science.gov (United States)

    Casper, Paul Henry

    1996-01-01

    When coupled with the prevailing ideas of cosmology, the standard model of particle physics implies that the early universe underwent a sequence of phase transitions. Such phase transitions can lead to topological defects such as magnetic monopoles, domain walls and cosmic strings. The formation and subsequent evolution of a network of cosmic strings may have played a key role in the development of the early universe. One of the most crucial elements in the evolution of the cosmic string network is the formation and decay of closed loops of cosmic string. After formation, the loops lose their energy by emitting gravitational radiation. This provides the primary energy loss mechanism for the cosmic string network. In addition, the cosmic string loops may display a number of observable features through which the cosmic string model may be constrained. In this dissertation a number of the key properties of cosmic string loops are investigated. A general method for determining the rates at which cosmic string loops radiate both energy and linear momentum is developed and implemented. Exact solutions for the radiation rates of a several new classes of loops are derived and used to test the validity of using the piecewise linear method on smooth loop trajectories. A large set of representative loop trajectories is produced using the method of loop fragmentation. These trajectories are analyzed to provide useful information on the properties of realistic cosmic string loops. The fraction of cosmic string loops which would collapse to form black holes is determined and used to place a new observational limit on the mass per unit length of cosmic strings.

  13. Comparative study of models of the recirculation loop with 10 jet pumps using different components in the code RELAP5/SCDAPSIM Mod.3.4; Estudio comparativo de modelos del lazo de recirculacion con 10 bombas chorro usando diferentes componentes en el codigo RELAP5/SCDAPSIM Mod.3.4

    Energy Technology Data Exchange (ETDEWEB)

    Araiza M, E.; Ortiz V, J., E-mail: enrique.araiza@inin.gob.mx [ININ, Departamento de Sistemas Nucleares, Carretera Mexico-Toluca s/n, 52750 Ocoyoacac, Estado de Mexico (Mexico)

    2012-10-15

    This work presents two arrangements in the nodal analysis of a recirculation loop for a BWR. Each one of these arrangements includes the ten jet pumps in each loop, instead of the traditional arrangement that consist of only jet pump representing to the ten pumps of a loop. The difference among the two models is presented mainly in the nodal analysis of the connection type cross-reduction, which takes charge of distributing the coolant flow to the lateral head stocks, where the vertical pipes (risers) that send the flow toward the jet pumps are connected. In the first arrangement the cross-reduction is modeled using the Branch component that is used in the interconnections simulation of hydrodynamic components. In the second arrangement the cross is simulated connecting the two distributor lateral head stocks with the main pipe of the loop by means of two simple unions that are modeled with the component SNGLJUN. The obtained results of the execution of both models are compared, taking important variables as reference, like pressures and mass expenses for the same components of both models. Finally these results are compared with the proportionate results by the traditional model. (Author)

  14. Bordetella parapertussis Circumvents Neutrophil Extracellular Bactericidal Mechanisms

    Science.gov (United States)

    Gorgojo, Juan; Scharrig, Emilia; Gómez, Ricardo M.; Harvill, Eric T.; Rodríguez, Maria Eugenia

    2017-01-01

    B. parapertussis is a whooping cough etiological agent with the ability to evade the immune response induced by pertussis vaccines. We previously demonstrated that in the absence of opsonic antibodies B. parapertussis hampers phagocytosis by neutrophils and macrophages and, when phagocytosed, blocks intracellular killing by interfering with phagolysosomal fusion. But neutrophils can kill and/or immobilize extracellular bacteria through non-phagocytic mechanisms such as degranulation and neutrophil extracellular traps (NETs). In this study we demonstrated that B. parapertussis also has the ability to circumvent these two neutrophil extracellular bactericidal activities. The lack of neutrophil degranulation was found dependent on the O antigen that targets the bacteria to cell lipid rafts, eventually avoiding the fusion of nascent phagosomes with specific and azurophilic granules. IgG opsonization overcame this inhibition of neutrophil degranulation. We further observed that B. parapertussis did not induce NETs release in resting neutrophils and inhibited NETs formation in response to phorbol myristate acetate (PMA) stimulation by a mechanism dependent on adenylate cyclase toxin (CyaA)-mediated inhibition of reactive oxygen species (ROS) generation. Thus, B. parapertussis modulates neutrophil bactericidal activity through two different mechanisms, one related to the lack of proper NETs-inducer stimuli and the other one related to an active inhibitory mechanism. Together with previous results these data suggest that B. parapertussis has the ability to subvert the main neutrophil bactericidal functions, inhibiting efficient clearance in non-immune hosts. PMID:28095485

  15. Extracellular quality control in the epididymis

    Institute of Scientific and Technical Information of China (English)

    Gail A. Cornwall; H. Henning von Horsten; Douglas Swartz; Seethal Johnson; Kim Chau; Sandra Whelly

    2007-01-01

    The epididymal lumen represents a unique extracellular environment because of the active sperm maturation process that takes place within its confines. Although much focus has been placed on the interaction of epididymal secretory proteins with spermatozoa in the lumen, very little is known regarding how the complex epididymal milieu as a whole is maintained, including mechanisms to prevent or control proteins that may not stay in their native folded state following secretion. Because some misfolded proteins can form cytotoxic aggregate structures known as amyloid, it is likely that control/surveillance mechanisms exist within the epididymis to protect against this process and allow sperm maturation to occur. To study protein aggregation and to identify extracellular quality control mechanisms in the epididymis, we used the cystatin family of cysteine protease inhibitors, including cystatin-related epididymal spermatogenic and cystatin C as molecular models because both proteins have inherent properties to aggregate and form amyloid. In this chapter, we present a brief summary of protein aggregation by the amyloid pathway based on what is known from other organ systems and describe quality control mechanisms that exist intracellularly to control protein misfolding and aggregation. We then present a summary of our studies of cystatinrelated epididymal spermatogenic (CRES) oligomerization within the epididymal lumen, including studies suggesting that transglutaminase cross-linking may be one mechanism of extracellular quality control within the epididymis.

  16. EXTRACELLULAR VESICLES: CLASSIFICATION, FUNCTIONS AND CLINICAL RELEVANCE

    Directory of Open Access Journals (Sweden)

    A. V. Oberemko

    2014-12-01

    Full Text Available This review presents a generalized definition of vesicles as bilayer extracellular organelles of all celular forms of life: not only eu-, but also prokaryotic. The structure and composition of extracellular vesicles, history of research, nomenclature, their impact on life processes in health and disease are discussed. Moreover, vesicles may be useful as clinical instruments for biomarkers, and they are promising as biotechnological drug. However, many questions in this area are still unresolved and need to be addressed in the future. The most interesting from the point of view of practical health care represents a direction to study the effect of exosomes and microvesicles in the development and progression of a particular disease, the possibility of adjusting the pathological process by means of extracellular vesicles of a particular type, acting as an active ingredient. Relevant is the further elucidation of the role and importance of exosomes to the surrounding cells, tissues and organs at the molecular level, the prospects for the use of non-cellular vesicles as biomarkers of disease.

  17. Extracellular conversion of adiponectin hexamers into trimers

    Science.gov (United States)

    Kim, Jeong-a; Nuñez, Martha; Briggs, David B.; Laskowski, Bethany L.; Chhun, Jimmy J.; Eleid, Joseph K.; Quon, Michael J.; Tsao, Tsu-Shuen

    2012-01-01

    Adiponectin is an adipocyte-secreted hormone that exists as trimers, hexamers and larger species collectively referred to as HMW (high-molecular-weight) adiponectin. Whether hexamers or HMW adiponectin serve as precursors for trimers outside the circulation is currently unknown. Here, we demonstrate that adiponectin trimers can be generated from larger oligomers secreted from primary rat adipose cells or differentiated 3T3-L1 adipocytes. Purified hexameric, but not HMW, adiponectin converted into trimers in conditioned media separated from 3T3-L1 adipocytes or, more efficiently, when enclosed in the dialysis membrane in the presence of adipocytes. Several lines of evidence indicate that the conversion is mediated by an extracellular redox system. First, N-terminal epitope-tagged hexamers converted into trimers without proteolytic removal of the tag. Secondly, appearance of trimers was associated with conversion of disulfide-bonded dimers into monomers. Thirdly, thiol-reactive agents inhibited conversion into trimers. Consistent with a redox-based mechanism, purified hexamers reductively converted into trimers in defined glutathione redox buffer with reduction potential typically found in the extracellular environment while the HMW adiponectin remained stable. In addition, conversion of hexamers into trimers was enhanced by NADPH, but not by NADP+. Collectively, these data strongly suggest the presence of an extracellular redox system capable of converting adiponectin oligomers. PMID:22973892

  18. Extracellular DNA: the tip of root defenses?

    Science.gov (United States)

    Hawes, Martha C; Curlango-Rivera, Gilberto; Wen, Fushi; White, Gerard J; Vanetten, Hans D; Xiong, Zhongguo

    2011-06-01

    This review discusses how extracellular DNA (exDNA) might function in plant defense, and at what level(s) of innate immunity this process might operate. A new role for extracellular factors in mammalian defense has been described in a series of studies. These studies reveal that cells including neutrophils, eosinophils, and mast cells produce 'extracellular traps' (ETs) consisting of histone-linked exDNA. When pathogens are attracted to such ETs, they are trapped and killed. When the exDNA component of ETs is degraded, trapping is impaired and resistance against invasion is reduced. Conversely, mutation of microbial genes encoding exDNases that degrade exDNA results in loss of virulence. This discovery that exDNases are virulence factors opens new avenues for disease control. In plants, exDNA is required for defense of the root tip. Innate immunity-related proteins are among a group of >100 proteins secreted from the root cap and root border cell populations. Direct tests revealed that exDNA also is rapidly synthesized and exported from the root tip. When this exDNA is degraded by the endonuclease DNase 1, root tip resistance to fungal infection is lost; when the polymeric structure is degraded more slowly, by the exonuclease BAL31, loss of resistance to fungal infection is delayed accordingly. The results suggest that root border cells may function in a manner analogous to that which occurs in mammalian cells.

  19. Extracellular matrix proteins involved in pseudoislets formation.

    Science.gov (United States)

    Maillard, Elisa; Sencier, Marie-Christine; Langlois, A; Bietiger, William; Krafft, Mp; Pinget, Michel; Sigrist, Séverine

    2009-01-01

    Extracellular matrix proteins are known to mediate, through integrins, cell adhesion and are involved in a number of cellular processes, including insulin expression and secretion in pancreatic islets. We investigated whether expression of some extracellular matrix proteins were implied in islets-like structure formation, named pseudoislets. For this purpose, we cultured the β-cell line, RINm5F, during 1, 3, 5 and 7 days of culture on treated or untreated culture plate to form adherent cells or pseudoislets and analysed insulin, collagen IV, fibronectin, laminin 5 and β1-integrin expression. We observed that insulin expression and secretion were increased during pseudoislets formation. Moreover, we showed by immunohistochemistry an aggregation of insulin secreting cells in the centre of the pseudoislets. Peripheral β-cells of pseudoislets did not express insulin after 7 days of culture. RT-PCR and immunohistochemistry studies showed a transient expression of type IV collagen in pseudoislets for the first 3 days of culture. Study of fibronectin expression indicated that adherent cells expressed more fibronectin than pseudoislets. In contrast, laminin 5 was more expressed in pseudoislets than in adherent cells. Finally, expression of β1-integrin was increased in pseudoislets as compared to adherent cells. In conclusion, laminin 5 and collagen IV might be implicated in pseudoislets formation whereas fibronectin might be involved in cell adhesion. These data suggested that extracellular matrix proteins may enhance the function of pseudoislets.

  20. Intracellular Biopotentials During Static Extracellular Stimulation

    Science.gov (United States)

    Klee, Maurice

    1973-01-01

    Two properties of the intracellular potentials and electric fields resulting from static extracellular stimulation are obtained for arbitrarily shaped cells. First, the values of intracellular potential are shown to be bounded by the maximum and minimum values of extracellular potential on the surface of the cell. Second, the volume average of the magnitude of intracellular electric field is shown to have an upper bound given by the ratio of the magnitude of the largest extracellular potential difference on the surface of the cell to a generalized length constant λ = [σintraVcell/(σmemb Acell)]1/2, where Vcell and Acell are the volume and surface area of the cell, σintra is the intracellular conductivity (reciprocal ohms per centimeter), and σmemb is the membrane conductivity (reciprocal ohms per square centimeter). The use of the upper bound on the volume average of the magnitude of intracellular electric field as an estimate for intracellular isopotentiality is discussed and the use of the generalized length constant for electrically describing arbitrary cells is illustrated for cylindrical- and spheroidal-shaped cells. PMID:4726882

  1. El Caucho

    Directory of Open Access Journals (Sweden)

    Brandes E. W.

    1942-12-01

    Full Text Available En tiempo de emergencia nacional el insignificante arbusto denominado Guayule se ha convertido en una importante fuente de producción cauchera. Después de años de permanecer a la sombra de su más renombrado competidor, el árbol de Hevea, el Guayule salió a la luz el 5 de marzo de 1942 cuando el Presidente Roosevelt firmó un decreto autorizando un programa oficial para la explotación del arbusto como medio de ampliar las fuentes de provisión de caucho de las Naciones Unidas.

  2. El Alcanfor

    Directory of Open Access Journals (Sweden)

    García Paredes Antonio

    1941-08-01

    Full Text Available El alcanfor es un cuerpo natural, pertenece al reino vegetal; es blanco, brillante, semitrasparente, aromático, duro, sólido, liviano, inflamable, volátil, pulverizable al ponerle unas gotas de alcohol, soluble en el alcohol y en los aceites, insoluble en el agua, medicinal e industrial. Entre los muchos vegetales que suministra alcanfor el más importante y antiguamente conocido es el Laurel Alcanfor, árbol centenario y frondoso de la familia de las Laurineas, propio del Japón y de la China.

  3. El perfume

    OpenAIRE

    Allegretti, Silvina A.

    2006-01-01

    El perfume (1985) relata la vida de Jean-Baptiste Grenouille, un ser proscrito nacido en el mercado de Les Halles. Como su madre intenta asesinarlo, el recién nacido es puesto bajo el amparo de varias nodrizas, que se deshacen de él – sistemáticamente- horrorizadas ante el niño que no despide “olor humano”. La ironía de la pluma creadora le asigna a Grenouille una contraparte especialísima: la criatura inodora tiene la capacidad de captar todos los aromas de París.

  4. Geometric Structures on Loop and Path Spaces

    Indian Academy of Sciences (India)

    Vicente Muñoz; Francisco Presas

    2010-09-01

    The loop space associated to a Riemannian manifold admits a quasi-symplectic structure (that is, a closed 2-form which is non-degenerate up to a finite-dimensional kernel). We show how to construct a compatible almost-complex structure. Finally conditions to have contact structures on loop spaces are studied.

  5. Holonomy loops, spectral triples and quantum gravity

    DEFF Research Database (Denmark)

    Johannes, Aastrup; Grimstrup, Jesper Møller; Nest, Ryszard

    2009-01-01

    We review the motivation, construction and physical interpretation of a semi-finite spectral triple obtained through a rearrangement of central elements of loop quantum gravity. The triple is based on a countable set of oriented graphs and the algebra consists of generalized holonomy loops...

  6. Newtonian gravity in loop quantum gravity

    OpenAIRE

    Smolin, Lee

    2010-01-01

    We apply a recent argument of Verlinde to loop quantum gravity, to conclude that Newton's law of gravity emerges in an appropriate limit and setting. This is possible because the relationship between area and entropy is realized in loop quantum gravity when boundaries are imposed on a quantum spacetime.

  7. Formation of Chromosomal Domains by Loop Extrusion

    Directory of Open Access Journals (Sweden)

    Geoffrey Fudenberg

    2016-05-01

    Full Text Available Topologically associating domains (TADs are fundamental structural and functional building blocks of human interphase chromosomes, yet the mechanisms of TAD formation remain unclear. Here, we propose that loop extrusion underlies TAD formation. In this process, cis-acting loop-extruding factors, likely cohesins, form progressively larger loops but stall at TAD boundaries due to interactions with boundary proteins, including CTCF. Using polymer simulations, we show that this model produces TADs and finer-scale features of Hi-C data. Each TAD emerges from multiple loops dynamically formed through extrusion, contrary to typical illustrations of single static loops. Loop extrusion both explains diverse experimental observations—including the preferential orientation of CTCF motifs, enrichments of architectural proteins at TAD boundaries, and boundary deletion experiments—and makes specific predictions for the depletion of CTCF versus cohesin. Finally, loop extrusion has potentially far-ranging consequences for processes such as enhancer-promoter interactions, orientation-specific chromosomal looping, and compaction of mitotic chromosomes.

  8. Vacuum Energy Sequestering and Graviton Loops

    CERN Document Server

    Kaloper, Nemanja

    2016-01-01

    We recently formulated a local mechanism of vacuum energy sequester. This mechanism automatically removes all matter loop contributions to vacuum energy from the stress energy tensor which sources the curvature. Here we adapt the local vacuum energy sequestering mechanism to also cancel all the vacuum energy loops involving virtual gravitons, in addition to the vacuum energy generated by matter fields alone.

  9. High-Order Frequency-Locked Loops

    DEFF Research Database (Denmark)

    Golestan, Saeed; Guerrero, Josep M.; Quintero, Juan Carlos Vasquez

    2017-01-01

    In very recent years, some attempts for designing high-order frequency-locked loops (FLLs) have been made. Nevertheless, the advantages and disadvantages of these structures, particularly in comparison with a standard FLL and high-order phase-locked loops (PLLs), are rather unclear. This lack......) as well as a unification between FLLs and PLLs is presented....

  10. Conformal anomaly of super Wilson loop

    Energy Technology Data Exchange (ETDEWEB)

    Belitsky, A.V., E-mail: andrei.belitsky@asu.edu [Department of Physics, Arizona State University, Tempe, AZ 85287-1504 (United States)

    2012-09-11

    Classically supersymmetric Wilson loop on a null polygonal contour possesses all symmetries required to match it onto non-MHV amplitudes in maximally supersymmetric Yang-Mills theory. However, to define it quantum mechanically, one is forced to regularize it since perturbative loop diagrams are not well defined due to presence of ultraviolet divergences stemming from integration in the vicinity of the cusps. A regularization that is adopted by practitioners by allowing one to use spinor helicity formalism, on the one hand, and systematically go to higher orders of perturbation theory is based on a version of dimensional regularization, known as Four-Dimensional Helicity scheme. Recently it was demonstrated that its use for the super Wilson loop at one loop breaks both conformal symmetry and Poincare supersymmetry. Presently, we exhibit the origin for these effects and demonstrate how one can undo this breaking. The phenomenon is alike the one emerging in renormalization group mixing of conformal operators in conformal theories when one uses dimensional regularization. The rotation matrix to the diagonal basis is found by means of computing the anomaly in the Ward identity for the conformal boost. Presently, we apply this ideology to the super Wilson loop. We compute the one-loop conformal anomaly for the super Wilson loop and find that the anomaly depends on its Grassmann coordinates. By subtracting this anomalous contribution from the super Wilson loop we restore its interpretation as a dual description for reduced non-MHV amplitudes which are expressed in terms of superconformal invariants.

  11. Design Principles for Closed Loop Supply Chains

    NARCIS (Netherlands)

    H.R. Krikke (Harold); C.P. Pappis (Costas); G.T. Tsoulfas; J.M. Bloemhof-Ruwaard (Jacqueline)

    2001-01-01

    textabstractIn this paper we study design principles for closed loop supply chains. Closed loop supply chains aim at closing material flows thereby limiting emission and residual waste, but also providing customer service at low cost. We study 'traditional' and 'new' design principles known in the l

  12. Loop approaches to gauge field theory

    NARCIS (Netherlands)

    Loll, R.

    1992-01-01

    Basic mathematical and physical concepts in loop- and path-dependent formulations of Yang-MiIls theory are reviewed and set into correspondence. We point out some problems peculiar to these non-local approaches, in particular those associated with defining structure on various kinds of loop

  13. External Tank CIL Closed Loop Verification System

    Science.gov (United States)

    Hartley, Eugene A., Jr.

    2005-01-01

    Lockheed Martin was requested to develop a closed loop CIL system following the Challenger accident. The system that was developed has proven to be very robust with minimal problems since implementation, having zero escapes in the last 7 years (27 External Tanks). We are currently investigating expansion of the CIL Closed Loop system to include "MI" CILs.

  14. Vacuum Energy Sequestering and Graviton Loops

    OpenAIRE

    Kaloper, Nemanja; Padilla, Antonio

    2016-01-01

    We recently formulated a local mechanism of vacuum energy sequester. This mechanism automatically removes all matter loop contributions to vacuum energy from the stress energy tensor which sources the curvature. Here we adapt the local vacuum energy sequestering mechanism to also cancel all the vacuum energy loops involving virtual gravitons, in addition to the vacuum energy generated by matter fields alone.

  15. New Matrix Loop Algebra and Its Application

    Institute of Scientific and Technical Information of China (English)

    DONG Huan-He; XU Yue-Cai

    2008-01-01

    A new matrix Lie algebra and its corresponding Loop algebra are constructed firstly, as its appfication, the multi-component TC equation hierarchy is obtained, then by use of trace identity the Hamiltonian structure of the above system is presented. Finally, the integrable couplings of the obtained system is worked out by the expanding matrix Loop algebra.

  16. Complete renormalization of QCD at five loops

    Science.gov (United States)

    Luthe, Thomas; Maier, Andreas; Marquard, Peter; Schröder, York

    2017-03-01

    We present new analytical five-loop Feynman-gauge results for the anomalous dimensions of ghost field and -vertex, generalizing the known values for SU(3) to a general gauge group. Together with previously published results on the quark mass and -field anomalous dimensions and the Beta function, this completes the 5-loop renormalization program of gauge theories in that gauge.

  17. Newtonian gravity in loop quantum gravity

    OpenAIRE

    Smolin, Lee

    2010-01-01

    We apply a recent argument of Verlinde to loop quantum gravity, to conclude that Newton's law of gravity emerges in an appropriate limit and setting. This is possible because the relationship between area and entropy is realized in loop quantum gravity when boundaries are imposed on a quantum spacetime.

  18. Design Principles for Closed Loop Supply Chains

    NARCIS (Netherlands)

    H.R. Krikke (Harold); C.P. Pappis (Costas); G.T. Tsoulfas; J.M. Bloemhof-Ruwaard (Jacqueline)

    2001-01-01

    textabstractIn this paper we study design principles for closed loop supply chains. Closed loop supply chains aim at closing material flows thereby limiting emission and residual waste, but also providing customer service at low cost. We study 'traditional' and 'new' design principles known in the

  19. Curcumin improves synaptic plasticity impairment induced by HIV-1gp120 V3 loop

    Directory of Open Access Journals (Sweden)

    Ling-ling Shen

    2015-01-01

    Full Text Available Curcumin has been shown to significantly improve spatial memory impairment induced by HIV-1 gp120 V3 in rats, but the electrophysiological mechanism remains unknown. Using extracellular microelectrode recording techniques, this study confirmed that the gp120 V3 loop could suppress long-term potentiation in the rat hippocampal CA1 region and synaptic plasticity, and that curcumin could antagonize these inhibitory effects. Using a Fura-2/AM calcium ion probe, we found that curcumin resisted the effects of the gp120 V3 loop on hippocampal synaptosomes and decreased Ca 2+ concentration in synaptosomes. This effect of curcumin was identical to nimodipine, suggesting that curcumin improved the inhibitory effects of gp120 on synaptic plasticity, ameliorated damage caused to the central nervous system, and might be a potential neuroprotective drug.

  20. Curcumin improves synaptic plasticity impairment induced by HIV-1gp120 V3 loop

    Institute of Scientific and Technical Information of China (English)

    Ling-ling Shen; Li-juan Yang; Ying Xu; Jun Dong; Ming-liang Jiang; Si-si Liu; Min-chun Cai; Zhong-qiu Hong; Li-qing Lin; Yan-yan Xing; Gui-lin Chen; Rui Pan

    2015-01-01

    Curcumin has been shown to significantly improve spatial memory impairment induced by HIV-1 gp120 V3 in rats, but the electrophysiological mechanism remains unknown. Using extra-cellular microelectrode recording techniques, this study conifrmed that the gp120 V3 loop could suppress long-term potentiation in the rat hippocampal CA1 region and synaptic plasticity, and that curcumin could antagonize these inhibitory effects. Using a Fura-2/AM calcium ion probe, we found that curcumin resisted the effects of the gp120 V3 loop on hippocampal synaptosomes and decreased Ca2+concentration in synaptosomes. This effect of curcumin was identical to nimodipine, suggesting that curcumin improved the inhibitory effects of gp120 on synaptic plasticity, ameliorated damage caused to the central nervous system, and might be a potential neuroprotective drug.

  1. El DISPOSITIVO Y EL SUJETO

    Directory of Open Access Journals (Sweden)

    Anton Voyame

    2015-06-01

    Full Text Available El siguiente artículo presenta como tema general la relación entre el concepto de dispositivo y el concepto de sujeto. A lo largo del desarrollo intentaremos responder a qué clase o tipo de relación se constituye entre ellos. Al interior de esa demarcación problemática, el objetivo principal de este artículo consiste en mostrar que el modo en que se piensan los dispositivos determina el modo en que se piensa al sujeto. Llevaremos adelante la investigación a través de un estudio de las características centrales del concepto de dispositivo. Y creemos que el aporte principal consiste en reflexionar sobre una serie de precauciones metodológicas para el abordaje de ambos conceptos, tanto del dispositivo como del sujeto, en la obra de Michel Foucault, durante la década de 1970. La exposición se divide en tres grandes conjuntos de elementos que podríamos describir del siguiente modo: 1 el carácter estratégico y tecnológico de los dispositivos, 2 la programación y la realización de los dispositivos, y 3 el modo en que se entiende la relación entre el dispositivo y el sujeto.

  2. Feedback Loop Gains and Feedback Behavior (1996)

    DEFF Research Database (Denmark)

    Kampmann, Christian Erik

    2012-01-01

    Linking feedback loops and system behavior is part of the foundation of system dynamics, yet the lack of formal tools has so far prevented a systematic application of the concept, except for very simple systems. Having such tools at their disposal would be a great help to analysts in understanding...... large, complicated simulation models. The paper applies tools from graph theory formally linking individual feedback loop strengths to the system eigenvalues. The significance of a link or a loop gain and an eigenvalue can be expressed in the eigenvalue elasticity, i.e., the relative change...... of an eigenvalue resulting from a relative change in the gain. The elasticities of individual links and loops may be found through simple matrix operations on the linearized system. Even though the number of feedback loops can grow rapidly with system size, reaching astronomical proportions even for modest systems...

  3. Damped transverse oscillations of interacting coronal loops

    CERN Document Server

    Soler, Roberto

    2015-01-01

    Damped transverse oscillations of magnetic loops are routinely observed in the solar corona. This phenomenon is interpreted as standing kink magnetohydrodynamic waves, which are damped by resonant absorption owing to plasma inhomogeneity across the magnetic field. The periods and damping times of these oscillations can be used to probe the physical conditions of the coronal medium. Some observations suggest that interaction between neighboring oscillating loops in an active region may be important and can modify the properties of the oscillations compared to those of an isolated loop. Here we theoretically investigate resonantly damped transverse oscillations of interacting non-uniform coronal loops. We provide a semi-analytic method, based on the T-matrix theory of scattering, to compute the frequencies and damping rates of collective oscillations of an arbitrary configuration of parallel cylindrical loops. The effect of resonant damping is included in the T-matrix scheme in the thin boundary approximation. ...

  4. Dynamic Model of Gap Loop for HCW Mill

    Institute of Scientific and Technical Information of China (English)

    YANG Jing-ming; YANG Qiu-xia; CHE Hai-jun; CHANG Ling-fang

    2004-01-01

    The hydraulic automatic gauge control system using gap loop for cold mill was designed. The stiffness of HCW cold mill was defined for gap loop, and the dynamic model of gauge control system for gap loop was built with mechanism analysis. The stiffness for gap loop and the cylinder displacement loop were measured.

  5. Loop A Is Critical for the Functional Interaction of Two Beta vulgaris PIP Aquaporins

    Science.gov (United States)

    Jozefkowicz, Cintia; Rosi, Pablo; Sigaut, Lorena; Soto, Gabriela; Pietrasanta, Lía Isabel; Amodeo, Gabriela; Alleva, Karina

    2013-01-01

    Research done in the last years strongly support the hypothesis that PIP aquaporin can form heterooligomeric assemblies, specially combining PIP2 monomers with PIP1 monomers. Nevertheless, the structural elements involved in the ruling of homo versus heterooligomeric organization are not completely elucidated. In this work we unveil some features of monomer-monomer interaction in Beta vulgaris PIP aquaporins. Our results show that while BvPIP2;2 is able to interact with BvPIP1;1, BvPIP2;1 shows no functional interaction. The lack of functional interaction between BvPIP2;1 and BvPIP1;1 was further corroborated by dose-response curves of water permeability due to aquaporin activity exposed to different acidic conditions. We also found that BvPIP2;1 is unable to translocate BvPIP1;1-ECFP from an intracellular position to the plasma membrane when co-expressed, as BvPIP2;2 does. Moreover we postulate that the first extracellular loop (loop A) of BvPIP2;1, could be relevant for the functional interaction with BvPIP1;1. Thus, we investigate BvPIP2;1 loop A at an atomic level by Molecular Dynamics Simulation (MDS) and by direct mutagenesis. We found that, within the tetramer, each loop A presents a dissimilar behavior. Besides, BvPIP2;1 loop A mutants restore functional interaction with BvPIP1;1. This work is a contribution to unravel how PIP2 and PIP1 interact to form functional heterooligomeric assemblies. We postulate that BvPIP2;1 loop A is relevant for the lack of functional interaction with BvPIP1;1 and that the monomer composition of PIP assemblies determines their functional properties. PMID:23483963

  6. Direct loop gain and bandwidth measurement of phase-locked loop

    Science.gov (United States)

    Ye, P.; Ren, R.; Kou, Y.; Sun, F.; Hu, J.; Chen, S.; Hou, D.

    2017-08-01

    A simple and robust technique for directly measuring the loop gain and bandwidth of a phase-locked loop (PLL) is proposed. This technique can be used for the real-time measurement of the real loop gain in a closed PLL without breaking its locking state. The agreement of the measured loop gain and theoretical calculations proves the validity of the proposed measurement technique. This technique with a simple configuration can be easily expanded to other phase-locking systems whose loop gain and bandwidth should be measured precisely.

  7. Cygnus Loop Supernova Blast Wave

    Science.gov (United States)

    1993-01-01

    This is an image of a small portion of the Cygnus Loop supernova remnant, which marks the edge of a bubble-like, expanding blast wave from a colossal stellar explosion, occurring about 15,000 years ago. The HST image shows the structure behind the shock waves, allowing astronomers for the first time to directly compare the actual structure of the shock with theoretical model calculations. Besides supernova remnants, these shock models are important in understanding a wide range of astrophysical phenomena, from winds in newly-formed stars to cataclysmic stellar outbursts. The supernova blast is slamming into tenuous clouds of insterstellar gas. This collision heats and compresses the gas, causing it to glow. The shock thus acts as a searchlight revealing the structure of the interstellar medium. The detailed HST image shows the blast wave overrunning dense clumps of gas, which despite HST's high resolution, cannot be resolved. This means that the clumps of gas must be small enough to fit inside our solar system, making them relatively small structures by interstellar standards. A bluish ribbon of light stretching left to right across the picture might be a knot of gas ejected by the supernova; this interstellar 'bullet' traveling over three million miles per hour (5 million kilometres) is just catching up with the shock front, which has slowed down by ploughing into interstellar material. The Cygnus Loop appears as a faint ring of glowing gases about three degrees across (six times the diameter of the full Moon), located in the northern constellation, Cygnus the Swan. The supernova remnant is within the plane of our Milky Way galaxy and is 2,600 light-years away. The photo is a combination of separate images taken in three colors, oxygen atoms (blue) emit light at temperatures of 30,000 to 60,000 degrees Celsius (50,000 to 100,000 degrees Farenheit). Hydrogen atoms (green) arise throughout the region of shocked gas. Sulfur atoms (red) form when the gas cools to

  8. Loop Staggering,Loop Compacting:Restructuring Techniques for Thrashing Problem

    Institute of Scientific and Technical Information of China (English)

    金国华; 杨学军; 等

    1993-01-01

    Parallel loops account for the greatest amount of parallelism in numerical programs.Executing nested loops in parallel wit low run-time overhead is thus very important for achieving high performance in paralleo processing systems.However,in parallel processing systems with caches of local memories in memory hierarchies,“thrashing problemmay” may arise when data move back and forth frequently between the caches or local memories in different processors.The techniques associated with parallel compiler to solve the problem are not completely developed.In this paper,we present two restructuring techniques called loopg staggering,loop staggering and compacting,with which we can not only eliminate the cache or local memory thrashing phemomena significantly,but also exploit the potential parallelism existing in outer serial loop.Loop staggering benefits the dynamic loop scheduling strategies,whereas loop staggering and compacting is good for static loop scheduling strategies,Our method especially benefits parallel programs,in which a parallel loop is enclosed by a serial loop and array elements are repeatedly used in the different iterations of the parallel loop.

  9. El loco y el idiota.

    Directory of Open Access Journals (Sweden)

    Alfredo Fierro Bardají

    1982-01-01

    Full Text Available El loco y el idiota -denominados así, según el uso cotidiano y vulgar, inmisericordemente despectivo -sin duda alguna son las dos figuras paradigmáticas de enajenación de la razón, el uno por desarreglo, el otro por defecto. El loco es el trastornado en su razón, el que se ha hecho un desbarajuste con un poder anímico esencialmente orientado a crear orden, a producir ideas claras y distintas. El idiota es el deficiente en su razón, el que participa de ella en medida tan escasa que se queda en un grado subhumano, a la altura de los brutos animales. La razón -una cierta determinación ideológica y práctica de la razón -crea al idiota y al loco como necesarios antagonistas para poder desarrollar su aventura histórica. Relegados a los rincones de la escena donde la razón occidental moderna despliega sus hazañas, en ningún modo son personajes secundarios de la historia. En su penumbra y su mutismo revelan sobre la razón secretos que ésta, en toda su cartesiana autoconciencia, nunca quiso ni pudo vislumbrar.

  10. Vibrio cholerae evades neutrophil extracellular traps by the activity of two extracellular nucleases.

    Directory of Open Access Journals (Sweden)

    Andrea Seper

    Full Text Available The Gram negative bacterium Vibrio cholerae is the causative agent of the secretory diarrheal disease cholera, which has traditionally been classified as a noninflammatory disease. However, several recent reports suggest that a V. cholerae infection induces an inflammatory response in the gastrointestinal tract indicated by recruitment of innate immune cells and increase of inflammatory cytokines. In this study, we describe a colonization defect of a double extracellular nuclease V. cholerae mutant in immunocompetent mice, which is not evident in neutropenic mice. Intrigued by this observation, we investigated the impact of neutrophils, as a central part of the innate immune system, on the pathogen V. cholerae in more detail. Our results demonstrate that V. cholerae induces formation of neutrophil extracellular traps (NETs upon contact with neutrophils, while V. cholerae in return induces the two extracellular nucleases upon presence of NETs. We show that the V. cholerae wild type rapidly degrades the DNA component of the NETs by the combined activity of the two extracellular nucleases Dns and Xds. In contrast, NETs exhibit prolonged stability in presence of the double nuclease mutant. Finally, we demonstrate that Dns and Xds mediate evasion of V. cholerae from NETs and lower the susceptibility for extracellular killing in the presence of NETs. This report provides a first comprehensive characterization of the interplay between neutrophils and V. cholerae along with new evidence that the innate immune response impacts the colonization of V. cholerae in vivo. A limitation of this study is an inability for technical and physiological reasons to visualize intact NETs in the intestinal lumen of infected mice, but we can hypothesize that extracellular nuclease production by V. cholerae may enhance survival fitness of the pathogen through NET degradation.

  11. Loops in exceptional field theory

    Energy Technology Data Exchange (ETDEWEB)

    Bossard, Guillaume [Centre de Physique Théorique, Ecole Polytechnique, CNRS, Université Paris-Saclay,91128 Palaiseau cedex (France); Kleinschmidt, Axel [Max-Planck-Institut für Gravitationsphysik (Albert-Einstein-Institut),Am Mühlenberg 1, DE-14476 Potsdam (Germany); International Solvay Institutes,ULB-Campus Plaine CP231, BE-1050 Brussels (Belgium)

    2016-01-27

    We study certain four-graviton amplitudes in exceptional field theory in dimensions D≥4 up to two loops. As the formulation is manifestly invariant under the U-duality group E{sub 11−D}(ℤ), our resulting expressions can be expressed in terms of automorphic forms. In the low energy expansion, we find terms in the M-theory effective action of type R{sup 4}, ∇{sup 4}R{sup 4} and ∇{sup 6}R{sup 4} with automorphic coefficient functions in agreement with independent derivations from string theory. This provides in particular an explicit integral formula for the exact string theory ∇{sup 6}R{sup 4} threshold function. We exhibit moreover that the usual supergravity logarithmic divergences cancel out in the full exceptional field theory amplitude, within an appropriately defined dimensional regularisation scheme. We also comment on terms of higher derivative order and the role of the section constraint for possible counterterms.

  12. Extracellular polymeric substances play roles in extracellular electron transfer of Shewanella oneidensis MR-1

    DEFF Research Database (Denmark)

    Xiao, Yong; Zhang, En-Hua; Christensen, Hans Erik Mølager

    It is well known that microorganism is surrounded by extracellular polymeric substances (EPS) which include polysaccharides, proteins, glycoproteins, nucleic acids, phospholipids, and humic acids. However, previous studies on microbial extracellular electron transfer (EET) are conducted on cells...... the extraction (Figure 1.a and 1.b). Comparing to cells in control group, MR-1 treated at 38 °C for EPS extraction showed different electrochemical characterizations as revealed by differential pulse voltammetry (Figure 1.c). EPS extracted from MR-1 also was proved to be electrochemically active. The present...

  13. Resorbable extracellular matrix grafts in urologic reconstruction

    Directory of Open Access Journals (Sweden)

    Richard A. Santucci

    2005-06-01

    Full Text Available PURPOSE: There is an increasingly large body of literature concerning tissue-engineering products that may be used in urology. Some of these are quite complex (such as multilayer patient-specific cell-seeded implants yet the most simple and successful products to date are also the most uncomplicated: resorbable acellular extra-cellular matrices (ECMs harvested from animals. ECMs have been used in a variety of difficult urologic reconstruction problems, and this review is intended to summarize this complex literature for the practicing urologist. METHODS: Medline search of related terms such as "SIS, small intestinal submucosa, ECM, extracellular matrix, acellular matrix and urologic reconstruction". Manuscripts missed in the initial search were taken from the bibliographies of the primary references. RESULTS: Full review of potential clinical uses of resorbable extra-cellular matrices in urologic reconstruction. CONCLUSIONS: Currently, the "state of the art" in tissue engineering solutions for urologic reconstruction means resorbable acellular xenograft matrices. They show promise when used as a pubovaginal sling or extra bolstering layers in ureteral or urethral repairs, although recent problems with inflammation following 8-ply pubovaginal sling use and failures after 1- and 4-ply SIS repair of Peyronie's disease underscore the need for research before wide adoption. Preliminary data is mixed concerning the potential for ECM urethral patch graft, and more data is needed before extended uses such as bladder augmentation and ureteral replacement are contemplated. The distant future of ECMs in urology likely will include cell-seeded grafts with the eventual hope of producing "off the shelf" replacement materials. Until that day arrives, ECMs only fulfill some of the requirements for the reconstructive urologist.

  14. Analysis and improvement of missile three-loop autopilots

    Institute of Scientific and Technical Information of China (English)

    Lin Defu; Fan Junfang; Qi Zaikang; Mou Yu

    2009-01-01

    characteristics from a two-loop autopilot with PI compensator.Both the two-loop and three-loop topologies can stabilize a static unstable missile.However,the finite actuator resource is the crucial factor dominating autopilot function.

  15. Mitotic chromosome compaction via active loop extrusion

    Science.gov (United States)

    Goloborodko, Anton; Imakaev, Maxim; Marko, John; Mirny, Leonid; MIT-Northwestern Team

    During cell division, two copies of each chromosome are segregated from each other and compacted more than hundred-fold into the canonical X-shaped structures. According to earlier microscopic observations and the recent Hi-C study, chromosomes are compacted into arrays of consecutive loops of ~100 kilobases. Mechanisms that lead to formation of such loop arrays are largely unknown. Here we propose that, during cell division, chromosomes can be compacted by enzymes that extrude loops on chromatin fibers. First, we use computer simulations and analytical modeling to show that a system of loop-extruding enzymes on a chromatin fiber self-organizes into an array of consecutive dynamic loops. Second, we model the process of loop extrusion in 3D and show that, coupled with the topo II strand-passing activity, it leads to robust compaction and segregation of sister chromatids. This mechanism of chromosomal condensation and segregation does not require additional proteins or specific DNA markup and is robust against variations in the number and properties of such loop extruding enzymes. Work at NU was supported by the NSF through Grants DMR-1206868 and MCB-1022117, and by the NIH through Grants GM105847 and CA193419. Work at MIT was supported by the NIH through Grants GM114190 R01HG003143.

  16. Managing Brain Extracellular K(+) during Neuronal Activity

    DEFF Research Database (Denmark)

    Larsen, Brian Roland; Stoica, Anca; MacAulay, Nanna

    2016-01-01

    reveal insights into pathological conditions such as epilepsy, migraine, and spreading depolarization following cerebral ischemia. In addition, particular neurological diseases occur as a result of mutations in the α2- (familial hemiplegic migraine type 2) and α3 isoforms (rapid-onset dystonia...... parkinsonism/alternating hemiplegia of childhood). This review addresses aspects of the Na(+)/K(+)-ATPase in the regulation of extracellular K(+) in the central nervous system as well as the related pathophysiology. Understanding the physiological setting in non-pathological tissue would provide a better...

  17. Biogenesis, delivery, and function of extracellular RNA

    Directory of Open Access Journals (Sweden)

    James G. Patton

    2015-08-01

    Full Text Available The Extracellular RNA (exRNA Communication Consortium was launched by the National Institutes of Health to focus on the extent to which RNA might function in a non-cell-autonomous manner. With the availability of increasingly sensitive tools, small amounts of RNA can be detected in serum, plasma, and other bodily fluids. The exact mechanism(s by which RNA can be secreted from cells and the mechanisms for the delivery and uptake by recipient cells remain to be determined. This review will summarize current knowledge about the biogenesis and delivery of exRNA and outline projects seeking to understand the functional impact of exRNA.

  18. Extracellular polymeric bacterial coverages as minimal surfaces

    CERN Document Server

    Saa, A; Saa, Alberto; Teschke, Omar

    2005-01-01

    Surfaces formed by extracellular polymeric substances enclosing individual and some small communities of {\\it Acidithiobacillus ferrooxidans} on plates of hydrophobic silicon and hydrophilic mica are analyzed by means of atomic force microscopy imaging. Accurate nanoscale descriptions of such coverage surfaces are obtained. The good agreement with the predictions of a rather simple but realistic theoretical model allows us to conclude that they correspond, indeed, to minimal area surfaces enclosing a given volume associated with the encased bacteria. This is, to the best of our knowledge, the first shape characterization of the coverage formed by these biomolecules, with possible applications to the study of biofilms.

  19. Bidirectional extracellular matrix signaling during tissue morphogenesis

    Science.gov (United States)

    Gjorevski, Nikolce; Nelson, Celeste M.

    2009-01-01

    Normal tissue development and function are regulated by the interplay between cells and their surrounding extracellular matrix (ECM). The ECM provides biochemical and mechanical contextual information that is conveyed from the cell membrane through the cytoskeleton to the nucleus to direct cell phenotype. Cells, in turn, remodel the ECM and thereby sculpt their local microenvironment. Here we review the mechanisms by which cells interact with, respond to, and influence the ECM, with particular emphasis placed on the role of this bidirectional communication during tissue morphogenesis. We also discuss the implications for successful engineering of functional tissues ex vivo. PMID:19896886

  20. Desnutrição materna durante a lactação em ratos Wistar: efeitos sobre as fibras elásticas da matriz extracelular na traqueia dos filhotes Maternal malnutrition during lactation in Wistar rats: effects on elastic fibers of the extracellular matrix in the trachea of offspring

    Directory of Open Access Journals (Sweden)

    Filipe Moreira de Andrade

    2012-10-01

    Full Text Available OBJETIVO: Investigar os efeitos da desnutrição proteica materna durante a lactação sobre as fibras elásticas da traqueia de filhotes de ratos Wistar. MÉTODOS: Ao nascimento, 12 filhotes machos de duas ratas Wistar foram igualmente divididos em dois grupos: grupo controle, cuja mãe recebeu água e dieta padrão de laboratório ad libitum durante a lactação, e grupo restrição proteica (RP, cuja mãe recebeu água ad libitum e dieta isoenergética com RP (8% de proteína. Aos 21 dias de vida, os filhotes foram sacrificados, e suas traqueias foram ressecadas. As fibras elásticas foram coradas pelo método de resorcina-fucsina de Weigert (precedido de oxidação e avaliadas sob microscopia óptica. As determinações morfométricas foram feitas por estereologia, utilizando o método de contagem de pontos, e expressas em densidade volumétrica. RESULTADOS: As fibras elásticas foram identificadas abaixo da mucosa traqueal, sendo a maioria em distribuição longitudinal. Além disso, camadas circulares bem definidas de fibras elásticas envolviam as superfícies interna e externa do anel cartilaginoso. Não houve diferenças entre os grupos quanto à organização e distribuição das fibras elásticas. A densidade volumétrica das fibras elásticas dos filhotes nos grupos controle e RP foi de, respectivamente, 2,46 ± 0,99% e 3,25 ± 1,13% (p OBJECTIVE: To investigate the effects of maternal protein malnutrition during lactation on the elastic fibers in the tracheas of Wistar rat pups. METHODS: At delivery, 12 male pups of two Wistar rat dams were equally divided into two groups: control, in which the dam received water and standard rat chow ad libitum during lactation; and protein-restricted (PR, in which the dam received water ad libitum and an isoenergetic PR diet (8% protein. At 21 days of age, the pups were killed and their tracheas were excised. The elastic fibers were stained with Weigert's resorcin-fuchsin (after oxidation and

  1. Remarks on correlators of Polyakov Loops

    CERN Document Server

    Neuberger, Herbert

    2013-01-01

    Polyakov loop eigenvalues and their N-dependence are studied in 2 and 4 dimensional SU(N) YM theory. The connected correlation function of the single eigenvalue distributions of two separated Polyakov loops in 2D YM is calculated and is found to have a structure differing from the one of corresponding hermitian random matrix ensembles. No large $N$ non-analyticities are found for two point functions in the confining regime. Suggestions are made for situations in which large-N phase transitions involving Polyakov loops might occur.

  2. Wilson Loop Form Factors: A New Duality

    OpenAIRE

    Chicherin, Dmitry; Heslop, Paul; Korchemsky, Gregory P.; Sokatchev, Emery

    2016-01-01

    We find a new duality for form factors of lightlike Wilson loops in planar $\\mathcal N=4$ super-Yang-Mills theory. The duality maps a form factor involving an $n$-sided lightlike polygonal super-Wilson loop together with $m$ external on-shell states, to the same type of object but with the edges of the Wilson loop and the external states swapping roles. This relation can essentially be seen graphically in Lorentz harmonic chiral (LHC) superspace where it is equivalent to planar graph duality....

  3. Construction of the blowdown and condensation loop

    Energy Technology Data Exchange (ETDEWEB)

    Park, Choon Kyung; Song, Chul Kyung; Cho, Seok; Chun, S. Y.; Chung, Moon Ki

    1997-12-01

    The blowdown and condensation loop (B and C loop) has been constructed to get experimental data for designing the safety depressurization system (SDS) and steam sparger which are considered to implement in the Korea Next Generation Reactor (KNGR). In this report, system description on the B and C loop is given in detail, which includes the drawings and technical specification of each component, instrumentation and control system, and the operational procedures and the results of the performance testing. (author). 7 refs., 11 tabs., 48 figs.

  4. Parallel Digital Phase-Locked Loops

    Science.gov (United States)

    Sadr, Ramin; Shah, Biren N.; Hinedi, Sami M.

    1995-01-01

    Wide-band microwave receivers of proposed type include digital phase-locked loops in which band-pass filtering and down-conversion of input signals implemented by banks of multirate digital filters operating in parallel. Called "parallel digital phase-locked loops" to distinguish them from other digital phase-locked loops. Systems conceived as cost-effective solution to problem of filtering signals at high sampling rates needed to accommodate wide input frequency bands. Each of M filters process 1/M of spectrum of signal.

  5. Loop-deformed Poincar\\'e algebra

    CERN Document Server

    Mielczarek, Jakub

    2013-01-01

    In this essay we present evidence suggesting that loop quantum gravity leads to deformation of the local Poincar\\'e algebra within the limit of high energies. This deformation is a consequence of quantum modification of effective off-shell hypersurface deformation algebra. Surprisingly, the form of deformation suggests that the signature of space-time changes from Lorentzian to Euclidean at large curvatures. We construct particular realization of the loop-deformed Poincar\\'e algebra and find that it can be related to curved momentum space, which indicates the relationship with recently introduced notion of relative locality. The presented findings open a new way of testing loop quantum gravity effects.

  6. El Despertar

    OpenAIRE

    Prada-Lara, Andrés José Renée

    2015-01-01

    Que tal si todo lo que nos rodea, nuestras realidades, acciones o destino, son monitoreados y hasta manipulados en el contexto de la lucha entre dos facciones que desde el principio de los tiempos, ciclos, o del espacio, han antagonizado. El bien o mal, la luz y la oscuridad, o como se les quiera denominar, han estado presentes para sacar lo mejor y lo peor de la humanidad. El hombre ha tratado de entender esta lucha y en ese contexto ha creado dioses, religiones y justificacio...

  7. Eigenvalue distributions of Wilson loops

    Energy Technology Data Exchange (ETDEWEB)

    Lohmayer, Robert

    2010-07-01

    In the first part of this thesis, we focus on the distribution of the eigenvalues of the unitary Wilson loop matrix in the two-dimensional case at arbitrary finite N. To characterize the distribution of the eigenvalues, we introduce three density functions (the ''symmetric'', the ''antisymmetric'', and the ''true'' eigenvalue density) which differ at finite N but possess the same infinite-N limit, exhibiting the Durhuus-Olesen phase transition. Using expansions of determinants and inverse determinants in characters of totally symmetric or totally antisymmetric representations of SU(N), the densities at finite N can be expressed in terms of simple sums involving only dimensions and quadratic Casimir invariants of certain irreducible representations of SU(N), allowing for a numerical computation of the densities at arbitrary N to any desired accuracy. We find that the true eigenvalue density, adding N oscillations to the monotonic symmetric density, is in some sense intermediate between the symmetric and the antisymmetric density, which in turn is given by a sum of N delta peaks located at the zeros of the average of the characteristic polynomial. Furthermore, we show that the dependence on N can be made explicit by deriving integral representations for the resolvents associated to the three eigenvalue densities. Using saddle-point approximations, we confirm that all three densities reduce to the Durhuus-Olesen result in the infinite-N limit. In the second part, we study an exponential form of the multiplicative random complex matrix model introduced by Gudowska-Nowak et al. Varying a parameter which can be identified with the area of the Wilson loop in the unitary case, the region of non-vanishing eigenvalue density of the N-dimensional complex product matrix undergoes a topological change at a transition point in the infinite-N limit. We study the transition by a detailed analysis of the average of the

  8. Defining the extracellular matrix using proteomics

    Science.gov (United States)

    Byron, Adam; Humphries, Jonathan D; Humphries, Martin J

    2013-01-01

    The cell microenvironment has a profound influence on the behaviour, growth and survival of cells. The extracellular matrix (ECM) provides not only mechanical and structural support to cells and tissues but also binds soluble ligands and transmembrane receptors to provide spatial coordination of signalling processes. The ability of cells to sense the chemical, mechanical and topographical features of the ECM enables them to integrate complex, multiparametric information into a coherent response to the surrounding microenvironment. Consequently, dysregulation or mutation of ECM components results in a broad range of pathological conditions. Characterization of the composition of ECM derived from various cells has begun to reveal insights into ECM structure and function, and mechanisms of disease. Proteomic methodologies permit the global analysis of subcellular systems, but extracellular and transmembrane proteins present analytical difficulties to proteomic strategies owing to the particular biochemical properties of these molecules. Here, we review advances in proteomic approaches that have been applied to furthering our understanding of the ECM microenvironment. We survey recent studies that have addressed challenges in the analysis of ECM and discuss major outcomes in the context of health and disease. In addition, we summarize efforts to progress towards a systems-level understanding of ECM biology. PMID:23419153

  9. Thermoreversible copolymer gels for extracellular matrix.

    Science.gov (United States)

    Vernon, B; Kim, S W; Bae, Y H

    2000-07-01

    To improve the properties of a reversible synthetic extracellular matrix based on a thermally reversible polymer, copolymers of N-isopropylacrylamide and acrylic acid were prepared in benzene with varying contents of acrylic acid (0 to 3%) and the thermal properties were evaluated. The poly(N-isopropylacrylamide) and copolymers made with acrylic acid had molecular weights from 0.8 to 1.7 x10(6) D. Differential scanning calorimetry (DSC) showed the high-molecular-weight acrylic acid copolymers had similar onset temperatures to the homopolymers, but the peak width was considerably increased with increasing acrylic acid content. DSC and cloud point measurements showed that polymers with 0 to 3% acrylic acid exhibit a lower critical solution temperature (LCST) transition between 30 degrees and 37 degrees C. In swelling studies, the homopolymer showed significant syneresis at temperatures above 31 degrees C. Copolymers with 1 and 1.5% showed syneresis beginning at 32 degrees and 37 degrees C, respectively. At 37 degrees C the copolymers with 1.5-3% acrylic acid showed little or no syneresis. Due to the high water content and a transition near physiologic conditions (below 37 degrees C), the polymers with 1.5-2.0% acrylic acid exhibited properties that would be useful in the development of a refillable synthetic extracellular matrix. Such a matrix could be applied to several cell types, including islets of Langerhans, for a biohybrid artificial pancreas.

  10. [Glutamic acid as a universal extracellular signal].

    Science.gov (United States)

    Yoneda, Yukio

    2015-08-01

    The prevailing view is that both glutamic (Glu) and gamma-aminobutyric (GABA) acids play a role as an amino acid neurotransmitter released from neurons. However, little attention has been paid to the possible expression and functionality of signaling machineries required for amino acidergic neurotransmission in cells other than central neurons. In line with our first demonstration of the presence of Glu receptors outside the brain, in this review I will outline our recent findings accumulated since then on the physiological and pathological significance of neuronal amino acids as an extracellular signal essential for homeostasis in a variety of phenotypic cells. In undifferentiated neural progenitor cells, for instance, functional expression is seen with different signaling machineries used for glutamatergic and GABAergic neurotransmission in neurons. Moreover, Glu plays a role in mechanisms underlying suppression of proliferation for self-replication in undifferentiated mesenchymal stem cells. There is more accumulating evidence for neuronal amino acids playing a role as an extracellular autocrine or paracrine signal commonly used in different phenotypic cells. Evaluation of drugs currently used could be thus beneficial for the efficient prophylaxis and/or the therapy of a variety of diseases relevant to disturbance of amino acid signaling in diverse organs.

  11. Extracellular superoxide dismutase of boar seminal plasma.

    Science.gov (United States)

    Kowalowka, M; Wysocki, P; Fraser, L; Strzezek, J

    2008-08-01

    Superoxide dismutase (SOD) is an enzymatic component of the antioxidant defense system that protects spermatozoa by catalysing the dismutation of superoxide anions to hydrogen peroxide and oxygen. Age and season effects on SOD activity in the seminal plasma were measured in boars at the onset of 8 months through a 35-month period. It was found that age-related changes in SOD activity in the seminal plasma were markedly higher in boars less than 2 years of age. However, it appeared that SOD activity was established at the early sexual maturity age (8-12 months). There were variations in SOD activity throughout the season, being significantly higher in spring and autumn than in summer. A secretory extracellular form of SOD (EC-SOD) was purified to homogeneity (350-fold) from boar seminal plasma, using a three-step purification protocol (affinity chromatography followed by ion exchange and ceramic hydroxyapatite chromatography). The molecular properties and specificity of SOD (molecular mass, isoelectric point, optimum pH, thermostability and susceptibility to inhibitors) confirmed that the purified enzyme is an extracellular form of Cu/Zn-superoxide dismutase occurring in boar seminal plasma. The results of this study indicate that EC-SOD is an important antioxidant enzyme of boar seminal plasma, which plays an important physiological role in counteracting oxidative stress in spermatozoa.

  12. Extracellular polymers of ozonized waste activated sludge.

    Science.gov (United States)

    Liu, J C; Lee, C H; Lai, J Y; Wang, K C; Hsu, Y C; Chang, B V

    2001-01-01

    Effect of ozonation on characteristics of waste activated sludge was investigated in the current study. Concentrations of cell-bound extracellular polymers (washed ECPs) did not change much upon ozonation, whereas the sum of cell-bound and soluble extracellular polymers (unwashed ECPs) increased with increasing ozone dose. Washed ECPs in original sludge as divided by molecular weight distribution was 39% 10,000 Da (high MW). It was observed that the low-MW fraction decreased, and the high-MW fraction increased in ozonized sludge. The unwashed ECPs were characterized as 44% in low MW, 30% in medium MW, and 26% in high MW. Both low-MW and medium-MW fractions of unwashed ECPs decreased while high-MW fraction increased in ozonized sludge. The dewaterability of ozonized sludge, assessed by capillary suction time (CST) and specific resistance to filtration (SRF), deteriorated with ozone dose. The optimal dose of cationic polyelectrolyte increased with increasing ozone dose. The production rate and the accumulated amount of methane gas of ozonized sludge were also higher.

  13. The International Society for Extracellular Vesicles launches the first massive open online course on extracellular vesicles

    Directory of Open Access Journals (Sweden)

    Cecilia Lässer

    2016-12-01

    Full Text Available The International Society for Extracellular Vesicles (ISEV has organised its first educational online course for students and beginners in the field of extracellular vesicles (EVs. This course, “Basics of Extracellular Vesicles,” uses recorded lectures from experts in the field and will be open for an unlimited number of participants. The course is divided into 5 modules and can be accessed at www.coursera.org/learn/extracellular-vesicles. The first module is an introduction to the field covering the nomenclature and history of EVs. Module 2 focuses on the biogenesis and uptake mechanisms of EVs, as well as their RNA, protein and lipid cargo. Module 3 covers the collection and processing of cell culture media and body fluids such as blood, breast milk, cerebrospinal fluid and urine prior to isolation of EVs. Modules 4 and 5 present different isolation methods and characterisation techniques utilised in the EV field. Here, differential ultracentrifugation, size-exclusion chromatography, density gradient centrifugation, kit-based precipitation, electron microscopy, cryo-electron microscopy, flow cytometry, atomic-force microscopy and nanoparticle-tracking analysis are covered. This first massive open online course (MOOC on EVs was launched on 15 August 2016 at the platform “Coursera” and is free of charge.

  14. Extracellular matrix in canine mammary tumors with special focus on versican, a versatile extracellular proteoglycan

    NARCIS (Netherlands)

    Erdélyi, Ildikó

    2006-01-01

    The extracellular matrix (ECM) research has become fundamental to understand cancer. This thesis focuses on the exploration of ECM composition and organization in canine mammary tumors, with a special interest in the large chondroitin-sulfate proteoglycan (PG), versican. Chapter 1 gives an overvie

  15. Interleukin-1 loop model for pathogenesis of Langerhans cell histiocytosis.

    Science.gov (United States)

    Murakami, Ichiro; Matsushita, Michiko; Iwasaki, Takeshi; Kuwamoto, Satoshi; Kato, Masako; Nagata, Keiko; Horie, Yasushi; Hayashi, Kazuhiko; Imamura, Toshihiko; Morimoto, Akira; Imashuku, Shinsaku; Gogusev, Jean; Jaubert, Francis; Takata, Katsuyoshi; Oka, Takashi; Yoshino, Tadashi

    2015-02-22

    We propose Langerhans cell histiocytosis (LCH) is an inflammatory process that is prolonged by mutations. We hypothesize that Merkel cell polyomavirus (MCPyV) infection triggers an interleukin-1 (IL-1) activation loop that underlies the pathogenesis of LCH. Langerhans cells (LCs) are antigen presenting cells in the skin. When LCs encounter exogenous antigens, they migrate from the epidermis into draining lymphoid tissues to initiate T-cell activity. It has been proposed that LC migration-related factors, including E-cadherin, matrix metalloproteinase, and Notch ligand induce LCH activity. We found that the tyrosine phosphatase SHP-1, which binds IL-1 receptor-associated kinase 1, is expressed at a significantly higher level in LCH affecting multiple organ systems (MS-LCH) than in LCH affecting a single organ system (SS-LCH). IL-1 stimulates T helper 17 cells and their signature cytokine IL-17 had been a matter of controversy. We detected higher levels of IL-17A receptor expression in MS-LCH than in SS-LCH and proposed an IL-17 endocrine model that could settle the controversy. IL-1 is the first cytokine secreted in response to sensitizers and promotes LC migration from sentinel tissues. Myeloid differentiation primary response 88 (MyD88), downstream of the IL-1 receptor, has functions in both RAS signaling and inflammation, leading to human cell transformation. In 2010, an activating mutation in the B-rapidly accelerated fibrosarcoma gene (BRAF) V600E was found in LCH. This BRAF mutation induces phosphorylation of the extracellular signal-regulated kinase (ERK) that may play an important role with MyD88 in LCH pathogenesis. However, phosphorylated ERK (pERK) is rapidly dephosphorylated by dual specificity phosphatase 6 (DUSP6), and limited proliferation is predicted in BRAF mutant cells. MyD88 binds pERK via its D-domain, thereby preventing pERK-DUSP6 interaction and maintaining ERK in an active, phosphorylated state. We detected MCPyV-DNA in the peripheral blood

  16. Integrand reduction beyond one-loop calculations

    CERN Document Server

    Ossola, Giovanni

    2016-01-01

    In this presentation, we review the general features of integrand-reduction techniques, with a particular focus on their generalization beyond one loop. We start with a brief discussion of the one-loop scenario, a case in which integrand-reduction algorithms are well established and played over the past decade an important role in the development of automated tools for the theoretical evaluation of physical observables. The generalization of integrand-reduction techniques to all loops has been the subject of several efforts in the recent past, thus providing a better understanding of the universal properties of scattering amplitudes. The ultimate goal of these studies is the development of efficient alternative computational techniques for the evaluation of Feynman integrals beyond one loop.

  17. Analytic three-loop static potential

    Science.gov (United States)

    Lee, Roman N.; Smirnov, Alexander V.; Smirnov, Vladimir A.; Steinhauser, Matthias

    2016-09-01

    We present analytic results for the three-loop static potential of two heavy quarks. The analytic calculation of the missing ingredients is outlined, and results for the singlet and octet potential are provided.

  18. Force distribution in a semiflexible loop

    CERN Document Server

    Waters, James T

    2016-01-01

    Loops undergoing thermal fluctuations are prevalent in nature. Ring-like or cross-linked polymers, cyclic macromolecules, and protein-mediated DNA loops all belong to this category. Stability of these molecules are generally described in terms of free energy, an average quantity, but it may also be impacted by local fluctuating forces acting within these systems. The full distribution of these forces can thus give us insights into mechanochemistry beyond the predictive capability of thermodynamics. In this paper, we study the force exerted by an inextensible semiflexible polymer constrained in a looped state. By using a novel simulation method termed "phase-space sampling", we generate the equilibrium distribution of chain conformations in both position and momentum space. We compute the constraint forces between the two ends of the loop in this chain ensemble using Lagrangian mechanics, and show that the mean of these forces is equal to the thermodynamic force. By analyzing kinetic and potential contribution...

  19. Quantum Loops in Non-Local Gravity

    CERN Document Server

    Talaganis, Spyridon

    2015-01-01

    In this proceedings, I will consider quantum aspects of a non-local, infinite-derivative scalar field theory - a ${\\it toy \\, model}$ depiction of a covariant infinite-derivative, non-local extension of Einstein's general relativity which has previously been shown to be free from ghosts around the Minkowski background. The graviton propagator in this theory gets an exponential suppression making it ${\\it asymptotically \\, free}$, thus providing strong prospects of resolving various classical and quantum divergences. In particular, I will find that at $1$-loop, the $2$-point function is still divergent, but once this amplitude is renormalized by adding appropriate counter terms, the ultraviolet (UV) behavior of all other $1$-loop diagrams as well as the $2$-loop, $2$-point function remains well under control. I will go on to discuss how one may be able to generalize our computations and arguments to arbitrary loops.

  20. Numerical multi-loop integrals and applications

    CERN Document Server

    Freitas, Ayres

    2016-01-01

    Higher-order radiative corrections play an important role in precision studies of the electroweak and Higgs sector, as well as for the detailed understanding of large backgrounds to new physics searches. For corrections beyond the one-loop level and involving many independent mass and momentum scales, it is in general not possible to find analytic results, so that one needs to resort to numerical methods instead. This article presents an overview over a variety of numerical loop integration techniques, highlighting their range of applicability, suitability for automatization, and numerical precision and stability. In a second part of this article, the application of numerical loop integration methods in the area of electroweak precision tests is illustrated. Numerical methods were essential for obtaining full two-loop predictions for the most important precision observables within the Standard Model. The theoretical foundations for these corrections will be described in some detail, including aspects of the r...

  1. Conformal anomaly of super Wilson loop

    CERN Document Server

    Belitsky, A V

    2012-01-01

    Classically supersymmetric Wilson loop on a null polygonal contour possesses all symmetries required to match it onto non-MHV amplitudes in maximally supersymmetric Yang-Mills theory. However, to define it quantum mechanically, one is forced to regularize it since perturbative loop diagrams are not well-defined due to presence of ultraviolet divergences stemming from integration in the vicinity of the cusps. A regularization that is adopted by practitioners by allowing one to use spinor helicity formalism, on the one hand, and systematically go to higher orders of perturbation theory is based on a version of dimensional regularization, known as Four-Dimensional Helicity scheme. Recently it was demonstrated that its use for the super Wilson loop at one loop breaks both conformal symmetry and Poincare supersymmetry. Presently, we exhibit the origin for these effects and demonstrate how one can undo this breaking. The phenomenon is alike the one emerging in renormalization group mixing of conformal operators in ...

  2. Introductory lectures to loop quantum gravity

    CERN Document Server

    Doná, Pietro

    2010-01-01

    We give a standard introduction to loop quantum gravity, from the ADM variables to spin network states. We include a discussion on quantum geometry on a fixed graph and its relation to a discrete approximation of general relativity.

  3. The Universal One-Loop Effective Action

    CERN Document Server

    Drozd, Aleksandra; Quevillon, Jérémie; You, Tevong

    2016-01-01

    We present the universal one-loop effective action for all operators of dimension up to six obtained by integrating out massive, non-degenerate multiplets. Our general expression may be applied to loops of heavy fermions or bosons, and has been checked against partial results available in the literature. The broad applicability of this approach simplifies one-loop matching from an ultraviolet model to a lower-energy effective field theory (EFT), a procedure which is now reduced to the evaluation of a combination of matrices in our universal expression, without any loop integrals to evaluate. We illustrate the relationship of our results to the Standard Model (SM) EFT, using as an example the supersymmetric stop and sbottom squark Lagrangian and extracting from our universal expression the Wilson coefficients of dimension-six operators composed of SM fields.

  4. Dimensionally continued multi-loop gauge theory

    CERN Document Server

    Broadhurst, D J

    1999-01-01

    A dimensionally continued background-field method makes the rationality of the 4-loop quenched QED beta function far more reasonable than had previously appeared. After 33 years of quest, dating from Rosner's discovery of 3-loop rationality, one finally sees cancellation of zeta values by the trace structure of individual diagrams. At 4-loops, diagram-by-diagram cancellation of $\\zeta(5)$ does not even rely on the values of integrals at d=4. Rather, it is a property of the rational functions of $d$ that multiply elements of the full d-dimensional basis. We prove a lemma: the basis consists of slices of wheels. We explain the previously mysterious suppression of $\\pi^4$ in massless gauge theory. The 4-loop QED result $\\beta_4=-46$ is obtained by setting d=4 in a precisely defined rational polynomial of d, with degree 11. The other 5 rational functions vanish at d=4.

  5. Energy release in driven twisted coronal loops

    CERN Document Server

    Bareford, M R; Browning, P K; Hood, A W

    2015-01-01

    In the present study we investigate magnetic reconnection in twisted magnetic fluxtubes with different initial configurations. In all considered cases, energy release is triggered by the ideal kink instability, which is itself the result of applying footpoint rotation to an initially potential field. The main goal of this work is to establish the influence of the field topology and various thermodynamic effects on the energy release process. Specifically, we investigate convergence of the magnetic field at the loop footpoints, atmospheric stratification, as well as thermal conduction. In all cases, the application of vortical driving at the footpoints of an initally potential field leads to an internal kink instability. With the exception of the curved loop with high footpoint convergence, the global geometry of the loop change little during the simulation. Footpoint convergence, curvature and atmospheric structure clearly influences the rapidity with which a loop achieves instability as well as the size of t...

  6. Loop Diuretics in the Treatment of Hypertension.

    Science.gov (United States)

    Malha, Line; Mann, Samuel J

    2016-04-01

    Loop diuretics are not recommended in current hypertension guidelines largely due to the lack of outcome data. Nevertheless, they have been shown to lower blood pressure and to offer potential advantages over thiazide-type diuretics. Torsemide offers advantages of longer duration of action and once daily dosing (vs. furosemide and bumetanide) and more reliable bioavailability (vs. furosemide). Studies show that the previously employed high doses of thiazide-type diuretics lower BP more than furosemide. Loop diuretics appear to have a preferable side effect profile (less hyponatremia, hypokalemia, and possibly less glucose intolerance). Studies comparing efficacy and side effect profiles of loop diuretics with the lower, currently widely prescribed, thiazide doses are needed. Research is needed to fill gaps in knowledge and common misconceptions about loop diuretic use in hypertension and to determine their rightful place in the antihypertensive arsenal.

  7. A theory of desynchronisable closed loop system

    Directory of Open Access Journals (Sweden)

    Harsh Beohar

    2010-10-01

    Full Text Available The task of implementing a supervisory controller is non-trivial, even though different theories exist that allow automatic synthesis of these controllers in the form of automata. One of the reasons for this discord is due to the asynchronous interaction between a plant and its controller in implementations, whereas the existing supervisory control theories assume synchronous interaction. As a consequence the implementation suffer from the so-called inexact synchronisation problem. In this paper we address the issue of inexact synchronisation in a process algebraic setting, by solving a more general problem of refinement. We construct an asynchronous closed loop system by introducing a communication medium in a given synchronous closed loop system. Our goal is to find sufficient conditions under which a synchronous closed loop system is branching bisimilar to its corresponding asynchronous closed loop system.

  8. A magnetohydrodynamic theory of coronal loop transients

    Science.gov (United States)

    Yeh, T.

    1982-01-01

    The physical and geometrical characteristics of solar coronal loop transients are described in an MHD model based on Archimedes' MHD buoyancy force. The theory was developed from interpretation of coronagraphic data, particularly from Skylab. The brightness of a loop is taken to indicate the electron density, and successive pictures reveal the electron enhancement in different columns. The forces which lift the loop off the sun surface are analyzed as an MHD buoyancy force affecting every mass element by imparting an inertial force necessary for heliocentrifugal motion. Thermal forces are responsible for transferring the ambient stress to the interior of the loop to begin the process. The kinematic and hydrostatic buoyancy overcome the gravitational force, and a flux rope can then curve upward, spiralling like a corkscrew with varying cross section around the unwinding solar magnetic field lines.

  9. Hardware-in-the-Loop Testing

    Data.gov (United States)

    Federal Laboratory Consortium — RTC has a suite of Hardware-in-the Loop facilities that include three operational facilities that provide performance assessment and production acceptance testing of...

  10. Off-shell two loop QCD vertices

    CERN Document Server

    Gracey, J A

    2014-01-01

    We calculate the triple gluon, ghost-gluon and quark-gluon vertex functions at two loops in the MSbar scheme in the chiral limit for an arbitrary linear covariant gauge when the external legs are all off-shell.

  11. Capillary fluid loop developments in Astrium

    Energy Technology Data Exchange (ETDEWEB)

    Figus, C.; Ounougha, L.; Bonzom, P. [Astrium SAS, Toulouse (France); Supper, W. [ESA/ESTEC, Noordwijk (Netherlands); Puillet, C. [CNES, Toulouse (France)

    2003-06-01

    Over the past decade, Astrium has been involved in the development of capillary pumped fluid loops. In the frame of the French technological demonstrator spacecraft called STENTOR, Astrium has gained experience on capillary fluid loop design and manufacturing. After the STENTOR cylindrical evaporator type was successfully tested and qualified, Astrium has developed miniaturised fluid loops for thermal dissipation of electronic devices. For such applications, the use of a flat shape evaporator is very promising, limiting the volume and the mass of the thermal hardware. Both technologies have been submitted to a comprehensive one-g test program and will be flight-tested in the near future. Through a comparative of the reached performances, some main advantages and drawbacks of each design are listed and a definition of what should be the next generation of Astrium fluid loops is given. (author)

  12. Modulation of DNA loop lifetimes by the free energy of loop formation

    CERN Document Server

    Chen, Yi-Ju; Mulligan, Peter; Spakowitz, Andrew J; Phillips, Rob

    2015-01-01

    Storage and retrieval of the genetic information in cells is a dynamic process that requires the DNA to undergo dramatic structural rearrangements. DNA looping is a prominent example of such a structural rearrangement that is essential for transcriptional regulation in both prokaryotes and eukaryotes, and the speed of such regulations affects the fitness of individuals. Here, we examine the in vitro looping dynamics of the classic Lac repressor gene-regulatory motif. We show that both loop association and loop dissociation at the DNA-repressor junctions depend on the elastic deformation of the DNA and protein, and that both looping and unlooping rates approximately scale with the looping J factor, which reflects the system's deformation free energy. We explain this observation by transition state theory and model the DNA-protein complex as an effective worm-like chain with twist. We introduce a finite protein-DNA binding interaction length, in competition with the characteristic DNA deformation length scale, ...

  13. A multiple-pass ring oscillator based dual-loop phase-locked loop

    Institute of Scientific and Technical Information of China (English)

    Chen Danfeng; Ren Junyan; Deng Jingjing; Li Wei; Li Ning

    2009-01-01

    A dual-loop phase-locked loop (PLL) for wideband operation is proposed. The dual-loop architecture combines a coarse-tuning loop with a fine-tuning one, enabling a wide tuning range and low voltage-controlled oscillator (VCO) gain without poisoning phase noise and reference spur suppression performance. An analysis of the phase noise and reference spur of the dual-loop PLL is emphasized. A novel multiple-pass ring VCO is designed for the dual-loop application. It utilizes both voltage-control and current-control simultaneously in the delay cell. The PLL is fabricated in Jazz 0.18-μm RF CMOS technology. The measured tuning range is from 4.2 to 5.9 GHz. It achieves a low phase noise of-99 dBc/Hz @ 1 MHz offset from a 5.5 GHz carrier.

  14. A multiple-pass ring oscillator based dual-loop phase-locked loop

    Energy Technology Data Exchange (ETDEWEB)

    Chen Danfeng; Ren Junyan; Deng Jingjing; Li Wei; Li Ning, E-mail: dfchen@fudan.edu.c [State Key Laboratory of ASIC and System, Fudan University, Shanghai 201203 (China)

    2009-10-15

    A dual-loop phase-locked loop (PLL) for wideband operation is proposed. The dual-loop architecture combines a coarse-tuning loop with a fine-tuning one, enabling a wide tuning range and low voltage-controlled oscillator (VCO) gain without poisoning phase noise and reference spur suppression performance. An analysis of the phase noise and reference spur of the dual-loop PLL is emphasized. A novel multiple-pass ring VCO is designed for the dual-loop application. It utilizes both voltage-control and current-control simultaneously in the delay cell. The PLL is fabricated in Jazz 0.18-{mu}m RF CMOS technology. The measured tuning range is from 4.2 to 5.9 GHz. It achieves a low phase noise of -99 dBc/Hz - 1 MHz offset from a 5.5 GHz carrier.

  15. Exponential Decay of Loop Lengths in the Loop O( n) Model with Large n

    Science.gov (United States)

    Duminil-Copin, Hugo; Peled, Ron; Samotij, Wojciech; Spinka, Yinon

    2017-02-01

    The loop O( n) model is a model for a random collection of non-intersecting loops on the hexagonal lattice, which is believed to be in the same universality class as the spin O( n) model. It has been conjectured that both the spin and the loop O( n) models exhibit exponential decay of correlations when n > 2. We verify this for the loop O( n) model with large parameter n, showing that long loops are exponentially unlikely to occur, uniformly in the edge weight x. Our proof provides further detail on the structure of typical configurations in this regime. Putting appropriate boundary conditions, when nx 6 is sufficiently small, the model is in a dilute, disordered phase in which each vertex is unlikely to be surrounded by any loops, whereas when nx 6 is sufficiently large, the model is in a dense, ordered phase which is a small perturbation of one of the three ground states.

  16. El secreto.

    Directory of Open Access Journals (Sweden)

    Victor Ricardo Torres Beltrán

    2012-04-01

    Full Text Available En el proceso evolutivo, la experiencia  ha demostrado que lo que en un momento inicial se acepta como verdad única, con el transcurrir del tiempo y después de repetirlo muchas veces, empieza a vislumbrarse con otras posibilidades que en el principio fueron consideradas erróneas. En su proceso evolutivo, la guitarra no ha alcanzado  aún su madurez,  en cuanto a su plenitud sonora, tal como la tienen el violín o el piano, entre otros instrumentos. Aquella posee un universo sonoro particular, el cual -con algunas excepciones-  no se ha  explotado en su totalidad,  pues  muchos compositores e intérpretes evitan los así llamados ";sonidos parásitos";, a los que los consideran desagradables, inútiles, o no musicales. Esto es relativo, dependiendo de cómo estén integrados en la obra y de cuál sea su intención expresiva, pues presentan una riqueza de posibilidades tímbricas, creando nuevos espacios de expresión -tanto en el ámbito tonal como en el atonal- son evocadores, e invitan a la creación.

  17. Rectangular Wilson Loops at Large N

    CERN Document Server

    Lohmayer, Robert

    2012-01-01

    This work is about pure Yang Mills theory in four Euclidean dimensions with gauge group SU(N). We study rectangular smeared Wilson loops on the lattice at large N and relatively close to the large-N transition point in their eigenvalue density. We show that the string tension can be extracted from these loops but obtain a shape dependence different from the prediction of effective string theory.

  18. Laser welding closed-loop power control

    DEFF Research Database (Denmark)

    Bagger, Claus; Olsen, Flemming Ove

    2003-01-01

    A closed-loop control system is developed to maintain an even seam width on the root side of a laser weld by continually controlling the output laser power of a 1500 W CO2 laser.......A closed-loop control system is developed to maintain an even seam width on the root side of a laser weld by continually controlling the output laser power of a 1500 W CO2 laser....

  19. Loop residues and catalysis in OMP synthase

    DEFF Research Database (Denmark)

    Wang, Gary P.; Hansen, Michael Riis; Grubmeyer, Charles

    2012-01-01

    (preceding paper in this issue, DOI 10.1021/bi300083p)]. The full expression of KIEs by H105A and E107A may result from a less secure closure of the catalytic loop. The lower level of expression of the KIE by K103A suggests that in these mutant proteins the major barrier to catalysis is successful closure...... of the catalytic loop, which when closed, produces rapid and reversible catalysis....

  20. Simple system for locating ground loops.

    Science.gov (United States)

    Bellan, P M

    2007-06-01

    A simple low-cost system for rapid identification of the cables causing ground loops in complex instrumentation configurations is described. The system consists of an exciter module that generates a 100 kHz ground loop current and a detector module that determines which cable conducts this test current. Both the exciter and detector are magnetically coupled to the ground circuit so there is no physical contact to the instrumentation system under test.

  1. Deployable radiator with flexible line loop

    Science.gov (United States)

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

    2003-01-01

    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).

  2. Zero Point Energy of Renormalized Wilson Loops

    OpenAIRE

    Hidaka, Yoshimasa; Pisarski, Robert D.

    2009-01-01

    The quark antiquark potential, and its associated zero point energy, can be extracted from lattice measurements of the Wilson loop. We discuss a unique prescription to renormalize the Wilson loop, for which the perturbative contribution to the zero point energy vanishes identically. A zero point energy can arise nonperturbatively, which we illustrate by considering effective string models. The nonperturbative contribution to the zero point energy vanishes in the Nambu model, but is nonzero wh...

  3. Master Symmetry for Holographic Wilson Loops

    CERN Document Server

    Klose, Thomas; Munkler, Hagen

    2016-01-01

    We identify the symmetry underlying the recently observed spectral-parameter transformations of holographic Wilson loops alias minimal surfaces in AdS/CFT. The generator of this nonlocal symmetry is shown to furnish a raising operator on the classical Yangian-type charges of symmetric coset models. We explicitly demonstrate how this master symmetry acts on strong-coupling Wilson loops and indicate a possible extension to arbitrary coupling.

  4. Laser welding closed-loop power control

    DEFF Research Database (Denmark)

    Bagger, Claus; Olsen, Flemming Ove

    2003-01-01

    A closed-loop control system is developed to maintain an even seam width on the root side of a laser weld by continually controlling the output laser power of a 1500 W CO2 laser.......A closed-loop control system is developed to maintain an even seam width on the root side of a laser weld by continually controlling the output laser power of a 1500 W CO2 laser....

  5. El ajo

    OpenAIRE

    Carda Paredes, Antonio

    2012-01-01

    El Ajo es del género ALLIUM, AJO, de la familia de las LILIACEAS. El ajo es una planta exótica, herbácea, anual, que fue traída de España junto con la cebolla, su congénere, en la época de la Colonia, y se aclimató muy bien en los climas fríos. El ajo es también planta bulbífera, y el bulbo llamado vulgarmente CABEZA está compuesto de varios bulbillos llamados DIENTES, cubiertos cada uno de una túnica muy delgada, seca y blanquecina. El olor del ajo es más fuerte y más difusible q...

  6. Multiple Flow Loop SCADA System Implemented on the Production Prototype Loop

    Energy Technology Data Exchange (ETDEWEB)

    Baily, Scott A. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Dalmas, Dale Allen [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Wheat, Robert Mitchell [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Woloshun, Keith Albert [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Dale, Gregory E. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-11-16

    The following report covers FY 15 activities to develop supervisory control and data acquisition (SCADA) system for the Northstar Moly99 production prototype gas flow loop. The goal of this effort is to expand the existing system to include a second flow loop with a larger production-sized blower. Besides testing the larger blower, this system will demonstrate the scalability of our solution to multiple flow loops.

  7. A note on two-loop superloop

    Science.gov (United States)

    Belitsky, A. V.

    2012-11-01

    We explore the duality between supersymmetric Wilson loop on null polygonal contours in maximally supersymmetric Yang-Mills theory and next-to-maximal helicity violating (NMHV) scattering amplitudes. Earlier analyses demonstrated that the use of a dimensional regulator for ultraviolet divergences, induced due to presence of the cusps on the loop, yields anomalies that break both conformal symmetry and supersymmetry. At one-loop order, these are present only in Grassmann components localized in the vicinity of a single cusp and result in a universal function for any number of sites of the polygon that can be subtracted away in a systematic manner leaving a well-defined supersymmetric remainder dual to corresponding components of the superamplitude. The question remains though whether components which were free from the aforementioned supersymmetric anomaly at leading order of perturbation theory remain so once computed at higher orders. Presently we verify this fact by calculating a particular component of the null polygonal super Wilson loop at two loops restricting the contour kinematics to a two-dimensional subspace. This allows one to perform all computations in a concise analytical form and trace the pattern of cancellations between individual Feynman graphs in a transparent fashion. As a consequence of our consideration we obtain a dual conformally invariant result for the remainder function in agreement with one-loop NMHV amplitudes.

  8. Space Station evolution study oxygen loop closure

    Science.gov (United States)

    Wood, M. G.; Delong, D.

    1993-01-01

    In the current Space Station Freedom (SSF) Permanently Manned Configuration (PMC), physical scars for closing the oxygen loop by the addition of oxygen generation and carbon dioxide reduction hardware are not included. During station restructuring, the capability for oxygen loop closure was deferred to the B-modules. As such, the ability to close the oxygen loop in the U.S. Laboratory module (LAB A) and the Habitation A module (HAB A) is contingent on the presence of the B modules. To base oxygen loop closure of SSF on the funding of the B-modules may not be desirable. Therefore, this study was requested to evaluate the necessary hooks and scars in the A-modules to facilitate closure of the oxygen loop at or subsequent to PMC. The study defines the scars for oxygen loop closure with impacts to cost, weight and volume and assesses the effects of byproduct venting. In addition, the recommended scenarios for closure with regard to topology and packaging are presented.

  9. El Ajo

    Directory of Open Access Journals (Sweden)

    Carda Paredes Antonio

    1942-08-01

    Full Text Available El Ajo es del género ALLIUM, AJO, de la familia de las LILIACEAS. El ajo es una planta exótica, herbácea, anual, que fue traída de España junto con la cebolla, su congénere, en la época de la Colonia, y se aclimató muy bien en los climas fríos. El ajo es también planta bulbífera, y el bulbo llamado vulgarmente CABEZA está compuesto de varios bulbillos llamados DIENTES, cubiertos cada uno de una túnica muy delgada, seca y blanquecina. El olor del ajo es más fuerte y más difusible que el de la cebolla y basta que se le despoje de su cubierta o película que lo cubre para que este olor se deje sentir vivamente a alguna distancia. Examinado químicamente el ajo, contiene las siguientes sustancias: mucílago, azúcar, azufre, sales y un aceite volátil amarillo muy acre y de sabor muy fuerte. A este aceite se atribuyen las propiedades excitantes del bulbo. El aceite volátil del ajo se extrae por destilación de los bulbos frescos. Este acéite contiene azufre y es más pesado que el agua. El ajo no es alimenticio pero es un condimento indispensable en todas las preparaciones del arte culinario.

  10. Initial binding of ions to the interhelical loops of divalent ion transporter CorA: replica exchange molecular dynamics simulation study.

    Directory of Open Access Journals (Sweden)

    Tong Zhang

    Full Text Available Crystal structures of Thermotoga maritima magnesium transporter CorA, reported in 2006, revealed its homo-pentameric constructions. However, the structure of the highly conserved extracellular interhelical loops remains unsolved, due to its high flexibility. We have explored the configurations of the loops through extensive replica exchange molecular dynamics simulations in explicit solvent model with the presence of either Co(III Hexamine ions or Mg(2+ ions. We found that there are multiple binding sites available on the interhelical loops in which the negatively charged residues, E316 and E320, are located notably close to the positively charged ions during the simulations. Our simulations resolved the distinct binding patterns of the two kinds of ions: Co(III Hexamine ions were found to bind stronger with the loop than Mg(2+ ions with binding free energy -7.3 kJ/mol lower, which is nicely consistent with the previous data. Our study provides an atomic basis description of the initial binding process of Mg(2+ ions on the extracellular interhelical loops of CorA and the detailed inhibition mechanism of Co(III Hexamine ions on CorA ions transportation.

  11. Initial binding of ions to the interhelical loops of divalent ion transporter CorA: replica exchange molecular dynamics simulation study.

    Science.gov (United States)

    Zhang, Tong; Mu, Yuguang

    2012-01-01

    Crystal structures of Thermotoga maritima magnesium transporter CorA, reported in 2006, revealed its homo-pentameric constructions. However, the structure of the highly conserved extracellular interhelical loops remains unsolved, due to its high flexibility. We have explored the configurations of the loops through extensive replica exchange molecular dynamics simulations in explicit solvent model with the presence of either Co(III) Hexamine ions or Mg(2+) ions. We found that there are multiple binding sites available on the interhelical loops in which the negatively charged residues, E316 and E320, are located notably close to the positively charged ions during the simulations. Our simulations resolved the distinct binding patterns of the two kinds of ions: Co(III) Hexamine ions were found to bind stronger with the loop than Mg(2+) ions with binding free energy -7.3 kJ/mol lower, which is nicely consistent with the previous data. Our study provides an atomic basis description of the initial binding process of Mg(2+) ions on the extracellular interhelical loops of CorA and the detailed inhibition mechanism of Co(III) Hexamine ions on CorA ions transportation.

  12. Loops In Proteins (LIP)--a comprehensive loop database for homology modelling.

    Science.gov (United States)

    Michalsky, E; Goede, A; Preissner, R

    2003-12-01

    One of the most important and challenging tasks in protein modelling is the prediction of loops, as can be seen in the large variety of existing approaches. Loops In Proteins (LIP) is a database that includes all protein segments of a length up to 15 residues contained in the Protein Data Bank (PDB). In this study, the applicability of LIP to loop prediction in the framework of homology modelling is investigated. Searching the database for loop candidates takes less than 1 s on a desktop PC, and ranking them takes a few minutes. This is an order of magnitude faster than most existing procedures. The measure of accuracy is the root mean square deviation (RMSD) with respect to the main-chain atoms after local superposition of target loop and predicted loop. Loops of up to nine residues length were modelled with a local RMSD <1 A and those of length up to 14 residues with an accuracy better than 2 A. The results were compared in detail with a thoroughly evaluated and tested ab initio method published recently and additionally with two further methods for a small loop test set. The LIP method produced very good predictions. In particular for longer loops it outperformed other methods.

  13. Hybrid Combustion-Gasification Chemical Looping

    Energy Technology Data Exchange (ETDEWEB)

    Herbert Andrus; Gregory Burns; John Chiu; Gregory Lijedahl; Peter Stromberg; Paul Thibeault

    2009-01-07

    For the past several years Alstom Power Inc. (Alstom), a leading world-wide power system manufacturer and supplier, has been in the initial stages of developing an entirely new, ultra-clean, low cost, high efficiency power plant for the global power market. This new power plant concept is based on a hybrid combustion-gasification process utilizing high temperature chemical and thermal looping technology The process consists of the oxidation, reduction, carbonation, and calcination of calcium-based compounds, which chemically react with coal, biomass, or opportunity fuels in two chemical loops and one thermal loop. The chemical and thermal looping technology can be alternatively configured as (i) a combustion-based steam power plant with CO{sub 2} capture, (ii) a hybrid combustion-gasification process producing a syngas for gas turbines or fuel cells, or (iii) an integrated hybrid combustion-gasification process producing hydrogen for gas turbines, fuel cells or other hydrogen based applications while also producing a separate stream of CO{sub 2} for use or sequestration. In its most advanced configuration, this new concept offers the promise to become the technology link from today's Rankine cycle steam power plants to tomorrow's advanced energy plants. The objective of this work is to develop and verify the high temperature chemical and thermal looping process concept at a small-scale pilot facility in order to enable AL to design, construct and demonstrate a pre-commercial, prototype version of this advanced system. In support of this objective, Alstom and DOE started a multi-year program, under this contract. Before the contract started, in a preliminary phase (Phase 0) Alstom funded and built the required small-scale pilot facility (Process Development Unit, PDU) at its Power Plant Laboratories in Windsor, Connecticut. Construction was completed in calendar year 2003. The objective for Phase I was to develop the indirect combustion loop with CO{sub 2

  14. Extracellular RNAs: development as biomarkers of human disease

    Directory of Open Access Journals (Sweden)

    Joseph F. Quinn

    2015-08-01

    Full Text Available Ten ongoing studies designed to test the possibility that extracellular RNAs may serve as biomarkers in human disease are described. These studies, funded by the NIH Common Fund Extracellular RNA Communication Program, examine diverse extracellular body fluids, including plasma, serum, urine and cerebrospinal fluid. The disorders studied include hepatic and gastric cancer, cardiovascular disease, chronic kidney disease, neurodegenerative disease, brain tumours, intracranial haemorrhage, multiple sclerosis and placental disorders. Progress to date and the plans for future studies are outlined.

  15. Neutrophils cast extracellular traps in response to protozoan parasites.

    Science.gov (United States)

    Abi Abdallah, Delbert S; Denkers, Eric Y

    2012-01-01

    Release of extracellular traps by neutrophils is a now well-established phenomenon that contributes to the innate response to extracellular bacterial and fungal pathogens. The importance of NETs during protozoan infection has been less explored, but recent findings suggest an emerging role for release of neutrophil-derived extracellular DNA in response to this class of microbial pathogens. The present review summarizes findings to date regarding elicitation of NETs by Toxoplasma gondii, Plasmodium falciparum, Eimeria bovis, and Leishmania spp.

  16. Fine-tuning of voltage sensitivity of the Kv1.2 potassium channel by interhelix loop dynamics.

    Science.gov (United States)

    Sand, Rheanna; Sharmin, Nazlee; Morgan, Carla; Gallin, Warren J

    2013-04-01

    Many proteins function by changing conformation in response to ligand binding or changes in other factors in their environment. Any change in the sequence of a protein, for example during evolution, which alters the relative free energies of the different functional conformations changes the conditions under which the protein will function. Voltage-gated ion channels are membrane proteins that open and close an ion-selective pore in response to changes in transmembrane voltage. The charged S4 transmembrane helix transduces changes in transmembrane voltage into a change in protein internal energy by interacting with the rest of the channel protein through a combination of non-covalent interactions between adjacent helices and covalent interactions along the peptide backbone. However, the structural basis for the wide variation in the V50 value between different voltage-gated potassium channels is not well defined. To test the role of the loop linking the S3 helix and the S4 helix in voltage sensitivity, we have constructed a set of mutants of the rat Kv1.2 channel that vary solely in the length and composition of the extracellular loop that connects S4 to S3. We evaluated the effect of these different loop substitutions on the voltage sensitivity of the channel and compared these experimental results with molecular dynamics simulations of the loop structures. Here, we show that this loop has a significant role in setting the precise V50 of activation in Kv1 family channels.

  17. The surface accessibility of the glycine receptor M2-M3 loop is increased in the channel open state.

    Science.gov (United States)

    Lynch, J W; Han, N L; Haddrill, J; Pierce, K D; Schofield, P R

    2001-04-15

    Mutations in the extracellular M2-M3 loop of the glycine receptor (GlyR) alpha1 subunit have been shown previously to affect channel gating. In this study, the substituted cysteine accessibility method was used to investigate whether a structural rearrangement of the M2-M3 loop accompanies GlyR activation. All residues from R271C to V277C were covalently modified by both positively charged methanethiosulfonate ethyltrimethylammonium (MTSET) and negatively charged methanethiosulfonate ethylsulfonate (MTSES), implying that these residues form an irregular surface loop. The MTSET modification rate of all residues from R271C to K276C was faster in the glycine-bound state than in the unliganded state. MTSES modification of A272C, L274C, and V277C was also faster in the glycine-bound state. These results demonstrate that the surface accessibility of the M2-M3 loop is increased as the channel transitions from the closed to the open state, implying that either the loop itself or an overlying domain moves during channel activation.

  18. The NIH Extracellular RNA Communication Consortium.

    Science.gov (United States)

    Ainsztein, Alexandra M; Brooks, Philip J; Dugan, Vivien G; Ganguly, Aniruddha; Guo, Max; Howcroft, T Kevin; Kelley, Christine A; Kuo, Lillian S; Labosky, Patricia A; Lenzi, Rebecca; McKie, George A; Mohla, Suresh; Procaccini, Dena; Reilly, Matthew; Satterlee, John S; Srinivas, Pothur R; Church, Elizabeth Stansell; Sutherland, Margaret; Tagle, Danilo A; Tucker, Jessica M; Venkatachalam, Sundar

    2015-01-01

    The Extracellular RNA (exRNA) Communication Consortium, funded as an initiative of the NIH Common Fund, represents a consortium of investigators assembled to address the critical issues in the exRNA research arena. The overarching goal is to generate a multi-component community resource for sharing fundamental scientific discoveries, protocols, and innovative tools and technologies. The key initiatives include (a) generating a reference catalogue of exRNAs present in body fluids of normal healthy individuals that would facilitate disease diagnosis and therapies, (b) defining the fundamental principles of exRNA biogenesis, distribution, uptake, and function, as well as development of molecular tools, technologies, and imaging modalities to enable these studies,

  19. Physiology and pathology of extracellular vesicules

    Directory of Open Access Journals (Sweden)

    M. A. Panteleev

    2017-01-01

    Full Text Available This year marks the 50th anniversary of the first publication about blood plasma microparticles. Initially considered as cell fragments or “platelet dust”, extracellular vesicles currently attracted the attention of biochemists, biophysicists, physicians, pharmacists around the world. They are heterogeneous in structure and derived from many cell types, express different antigen and contain variety of biomolecules that determines wide range of biological activity, including procoagulant, regenerative, immunomodulating, and others. They play an important role in the pathophysiology of different diseases and conditions – from infarction, injuries and pregnancies to the “graft versus host” disease. The vesicles as medicaments and their carriers, as well as the drugs that affect them, are a rapidly developing field of research.

  20. Extracellular Matrices (ECM) for Tissue Repair.

    Science.gov (United States)

    Polanco, Thais O; Xylas, Joanna; Lantis, John C

    2016-04-01

    Persistence of skin wounds due to underlying disease, bacterial contamination, and/or repeated trauma, causes a chronic condition where a functional extracellular matrix (ECM) cannot be established and the normal wound-healing cascade is unable to progress. These open chronic wounds leave the body susceptible to infection and present a major healthcare problem. To this end, a broad range of biologic ECM scaffolds have been developed that can provide other therapeutic options aside from traditional wound care approaches. These tissue engineered ECM scaffolds aim to facilitate the restoration of functional skin-like tissue by altering the chronic wound environment and facilitating cellular attachment, proliferation, and differentiation. This discussion will center on reviewing current ECM scaffolds and highlighting their properties and mechanism of action with respect to the clinical application in chronic, non-healing wounds.

  1. Neutrophil extracellular traps in tissue pathology.

    Science.gov (United States)

    Nakazawa, Daigo; Kumar, Santosh; Desai, Jyaysi; Anders, Hans-Joachim

    2017-03-01

    Neutrophil extracellular traps (NETs) are innate immune systems against invading pathogens. NETs are characterized as released DNA mixed with cytoplasmic antimicrobial proteins such as myeloperoxidase, proteinase3 and neutrophil elastase. While NETs are thought to have an important role in host defense, recent work has suggested that NETs contribute to tissue injury in non-infectious disease states. Uncontrolled NET formation in autoimmune diseases, metabolic disorders, cancers and thrombotic diseases can exacerbate a disease or even be a major initiator of tissue injury. But spotting NETs in tissues is not easy. Here we review the available histopathological evidence on the presence of NETs in a variety of diseases. We discuss technical difficulties and potential sources of misinterpretation while trying to detect NETs in tissue samples.

  2. Extracellular nicotinamide phosphoribosyltransferase, a new cancer metabokine

    Science.gov (United States)

    Grolla, Ambra A; Travelli, Cristina

    2016-01-01

    Abstract In this review, we focus on the secreted form of nicotinamide phosphoribosyltransferase (NAMPT); extracellular NAMPT (eNAMPT), also known as pre‐B cell colony‐enhancing factor or visfatin. Although intracellular NAMPT is a key enzyme in controlling NAD metabolism, eNAMPT has been reported to function as a cytokine, with many roles in physiology and pathology. Circulating eNAMPT has been associated with several metabolic and inflammatory disorders, including cancer. Because cytokines produced in the tumour micro‐environment play an important role in cancer pathogenesis, in part by reprogramming cellular metabolism, future improvements in cancer immunotherapy will require a better understanding of the crosstalk between cytokine action and tumour biology. In this review, the knowledge of eNAMPT in cancer will be discussed, focusing on its immunometabolic function as a metabokine, its secretion, its mechanism of action and possible roles in the cancer micro‐environment. PMID:27128025

  3. Extracellular Vesicles in Chronic Obstructive Pulmonary Disease

    Directory of Open Access Journals (Sweden)

    Tsukasa Kadota

    2016-10-01

    Full Text Available Chronic obstructive pulmonary disease (COPD is characterized by the progression of irreversible airflow limitation and is a leading cause of morbidity and mortality worldwide. Although several crucial mechanisms of COPD pathogenesis have been studied, the precise mechanism remains unknown. Extracellular vesicles (EVs, including exosomes, microvesicles, and apoptotic bodies, are released from almost all cell types and are recognized as novel cell–cell communication tools. They have been shown to carry and transfer a wide variety of molecules, such as microRNAs, messenger RNAs, and proteins, which are involved in physiological functions and the pathology of various diseases. Recently, EVs have attracted considerable attention in pulmonary research. In this review, we summarize the recent findings of EV-mediated COPD pathogenesis. We also discuss the potential clinical usefulness of EVs as biomarkers and therapeutic agents for the treatment of COPD.

  4. Extracellular Matrix Molecules Facilitating Vascular Biointegration

    Directory of Open Access Journals (Sweden)

    Martin K.C. Ng

    2012-08-01

    Full Text Available All vascular implants, including stents, heart valves and graft materials exhibit suboptimal biocompatibility that significantly reduces their clinical efficacy. A range of biomolecules in the subendothelial space have been shown to play critical roles in local regulation of thrombosis, endothelial growth and smooth muscle cell proliferation, making these attractive candidates for modulation of vascular device biointegration. However, classically used biomaterial coatings, such as fibronectin and laminin, modulate only one of these components; enhancing endothelial cell attachment, but also activating platelets and triggering thrombosis. This review examines a subset of extracellular matrix molecules that have demonstrated multi-faceted vascular compatibility and accordingly are promising candidates to improve the biointegration of vascular biomaterials.

  5. Active endocannabinoids are secreted on extracellular membrane vesicles.

    Science.gov (United States)

    Gabrielli, Martina; Battista, Natalia; Riganti, Loredana; Prada, Ilaria; Antonucci, Flavia; Cantone, Laura; Matteoli, Michela; Maccarrone, Mauro; Verderio, Claudia

    2015-02-01

    Endocannabinoids primarily influence neuronal synaptic communication within the nervous system. To exert their function, endocannabinoids need to travel across the intercellular space. However, how hydrophobic endocannabinoids cross cell membranes and move extracellularly remains an unresolved problem. Here, we show that endocannabinoids are secreted through extracellular membrane vesicles produced by microglial cells. We demonstrate that microglial extracellular vesicles carry on their surface N-arachidonoylethanolamine (AEA), which is able to stimulate type-1 cannabinoid receptors (CB1), and inhibit presynaptic transmission, in target GABAergic neurons. This is the first demonstration of a functional role of extracellular vesicular transport of endocannabinoids.

  6. El Sufismo y el Islam

    Directory of Open Access Journals (Sweden)

    Gamal Abdel-Karim

    2015-03-01

    Full Text Available La experiencia sufí es el encuentro con la verdad absoluta, y esa verdad no puede convertirse en feudo ni monopolio de nadie y para nadie, y tampoco está limitada a una cultura, raza o creencia concreta. La doctrina del sufismo consiste en que el hombre se entrega voluntariamente en cuerpo y alma a Dios. Estos ascetas y místicos sufíes lo hacen, unos en solitario y otros en retiros colectivos de asociaciones místicas llamadas turuq, como miembros seguidores de un maestro (Shaykh que les permitía llevar una vida normal y austera compatible con determinadas normas y prácticas ascéticas de acuerdo con el criterio de cada tariqa (camino iniciático místico. Así, el sufismo se convirtió en el Islam perfecto, bajo la dirección de sus maestros y guías espirituales (shuyukh experimentados y en asociaciones piadosas donde se impartían enseñanzas y prácticas sufíes. En la experiencia mística del sufismo llega la religiosidad árabe-musulmana a su perfección: en el ella el ser humano se entrega a Dios, se libera del engaño de lo inmediato y se siente unido a Dios en el universo como inmensa luz que manifiesta su grandeza.

  7. Bioengineering Human Myocardium on Native Extracellular Matrix

    Science.gov (United States)

    Guyette, Jacques P.; Charest, Jonathan M; Mills, Robert W; Jank, Bernhard J.; Moser, Philipp T.; Gilpin, Sarah E.; Gershlak, Joshua R.; Okamoto, Tatsuya; Gonzalez, Gabriel; Milan, David J.; Gaudette, Glenn R.; Ott, Harald C.

    2015-01-01

    Rationale More than 25 million individuals suffer from heart failure worldwide, with nearly 4,000 patients currently awaiting heart transplantation in the United States. Donor organ shortage and allograft rejection remain major limitations with only about 2,500 hearts transplanted each year. As a theoretical alternative to allotransplantation, patient-derived bioartificial myocardium could provide functional support and ultimately impact the treatment of heart failure. Objective The objective of this study is to translate previous work to human scale and clinically relevant cells, for the bioengineering of functional myocardial tissue based on the combination of human cardiac matrix and human iPS-derived cardiac myocytes. Methods and Results To provide a clinically relevant tissue scaffold, we translated perfusion-decellularization to human scale and obtained biocompatible human acellular cardiac scaffolds with preserved extracellular matrix composition, architecture, and perfusable coronary vasculature. We then repopulated this native human cardiac matrix with cardiac myocytes derived from non-transgenic human induced pluripotent stem cells (iPSCs) and generated tissues of increasing three-dimensional complexity. We maintained such cardiac tissue constructs in culture for 120 days to demonstrate definitive sarcomeric structure, cell and matrix deformation, contractile force, and electrical conduction. To show that functional myocardial tissue of human scale can be built on this platform, we then partially recellularized human whole heart scaffolds with human iPSC-derived cardiac myocytes. Under biomimetic culture, the seeded constructs developed force-generating human myocardial tissue, showed electrical conductivity, left ventricular pressure development, and metabolic function. Conclusions Native cardiac extracellular matrix scaffolds maintain matrix components and structure to support the seeding and engraftment of human iPS-derived cardiac myocytes, and enable

  8. Filter based phase distortions in extracellular spikes.

    Science.gov (United States)

    Yael, Dorin; Bar-Gad, Izhar

    2017-01-01

    Extracellular recordings are the primary tool for extracting neuronal spike trains in-vivo. One of the crucial pre-processing stages of this signal is the high-pass filtration used to isolate neuronal spiking activity. Filters are characterized by changes in the magnitude and phase of different frequencies. While filters are typically chosen for their effect on magnitudes, little attention has been paid to the impact of these filters on the phase of each frequency. In this study we show that in the case of nonlinear phase shifts generated by most online and offline filters, the signal is severely distorted, resulting in an alteration of the spike waveform. This distortion leads to a shape that deviates from the original waveform as a function of its constituent frequencies, and a dramatic reduction in the SNR of the waveform that disrupts spike detectability. Currently, the vast majority of articles utilizing extracellular data are subject to these distortions since most commercial and academic hardware and software utilize nonlinear phase filters. We show that this severe problem can be avoided by recording wide-band signals followed by zero phase filtering, or alternatively corrected by reversed filtering of a narrow-band filtered, and in some cases even segmented signals. Implementation of either zero phase filtering or phase correction of the nonlinear phase filtering reproduces the original spike waveforms and increases the spike detection rates while reducing the number of false negative and positive errors. This process, in turn, helps eliminate subsequent errors in downstream analyses and misinterpretations of the results.

  9. Filter based phase distortions in extracellular spikes

    Science.gov (United States)

    Yael, Dorin

    2017-01-01

    Extracellular recordings are the primary tool for extracting neuronal spike trains in-vivo. One of the crucial pre-processing stages of this signal is the high-pass filtration used to isolate neuronal spiking activity. Filters are characterized by changes in the magnitude and phase of different frequencies. While filters are typically chosen for their effect on magnitudes, little attention has been paid to the impact of these filters on the phase of each frequency. In this study we show that in the case of nonlinear phase shifts generated by most online and offline filters, the signal is severely distorted, resulting in an alteration of the spike waveform. This distortion leads to a shape that deviates from the original waveform as a function of its constituent frequencies, and a dramatic reduction in the SNR of the waveform that disrupts spike detectability. Currently, the vast majority of articles utilizing extracellular data are subject to these distortions since most commercial and academic hardware and software utilize nonlinear phase filters. We show that this severe problem can be avoided by recording wide-band signals followed by zero phase filtering, or alternatively corrected by reversed filtering of a narrow-band filtered, and in some cases even segmented signals. Implementation of either zero phase filtering or phase correction of the nonlinear phase filtering reproduces the original spike waveforms and increases the spike detection rates while reducing the number of false negative and positive errors. This process, in turn, helps eliminate subsequent errors in downstream analyses and misinterpretations of the results. PMID:28358895

  10. Ciliary extracellular vesicles: Txt msg orgnlls

    Science.gov (United States)

    Wang, Juan; Barr, Maureen M.

    2016-01-01

    Cilia are sensory organelles that protrude from cell surfaces to monitor the surrounding environment. In addition to its role as sensory receiver, the cilium also releases extracellular vesicles (EVs). The release of sub-micron sized EVs is a conserved form of intercellular communication used by all three kingdoms of life. These extracellular organelles play important roles in both short and long range signaling between donor and target cells and may coordinate systemic responses within an organism in normal and diseased states. EV shedding from ciliated cells and EV-cilia interactions are evolutionarily conserved phenomena, yet remarkably little is known about the relationship between the cilia and EVs and the fundamental biology of EVs. Studies in the model organisms Chlamydomonas and C. elegans have begun to shed light on ciliary EVs. Chlamydomonas EVs are shed from tips of flagella and are bioactive. C. elegans EVs are shed and released by ciliated sensory neurons in an intraflagellar transport (IFT)-dependent manner. C. elegans EVs play a role in modulating animal-to-animal communication, and this EV bioactivity is dependent on EV cargo content. Some ciliary pathologies, or ciliopathies, are associated with abnormal EV shedding or with abnormal cilia-EV interactions, suggest the cilium may be an important organelle as an EV donor or as an EV target. Until the past few decades, both cilia and EVs were ignored as vestigial or cellular junk. As research interest in these two organelles continues to gain momentum, we envision a new field of cell biology emerging. Here, we propose that the cilium is a dedicated organelle for EV biogenesis and EV reception. We will also discuss possible mechanisms by which EVs exert bioactivity and explain how what is learned in model organisms regarding EV biogenesis and function may provide insight to human ciliopathies. PMID:26983828

  11. Role of extracellular superoxide dismutase in hypertension.

    Science.gov (United States)

    Gongora, Maria Carolina; Qin, Zhenyu; Laude, Karine; Kim, Ha Won; McCann, Louise; Folz, J Rodney; Dikalov, Sergey; Fukai, Tohru; Harrison, David G

    2006-09-01

    We previously found that angiotensin II-induced hypertension increases vascular extracellular superoxide dismutase (ecSOD), and proposed that this is a compensatory mechanism that blunts the hypertensive response and preserves endothelium-dependent vasodilatation. To test this hypothesis, we studied ecSOD-deficient mice. ecSOD(-/-) and C57Blk/6 mice had similar blood pressure at baseline; however, the hypertension caused by angiotensin II was greater in ecSOD(-/-) compared with wild-type mice (168 versus 147 mm Hg, respectively; P<0.01). In keeping with this, angiotensin II increased superoxide and reduced endothelium-dependent vasodilatation in small mesenteric arterioles to a greater extent in ecSOD(-/-) than in wild-type mice. In contrast to these findings in resistance vessels, angiotensin II paradoxically improved endothelium-dependent vasodilatation, reduced intracellular and extracellular superoxide, and increased NO production in aortas of ecSOD(-/-) mice. Whereas aortic expression of endothelial NO synthase, Cu/ZnSOD, and MnSOD were not altered in ecSOD(-/-) mice, the activity of Cu/ZnSOD was increased by 80% after angiotensin II infusion. This was associated with a concomitant increase in expression of the copper chaperone for Cu/ZnSOD in the aorta but not in the mesenteric arteries. Moreover, the angiotensin II-induced increase in aortic reduced nicotinamide-adenine dinucleotide phosphate oxidase activity was diminished in ecSOD(-/-) mice as compared with controls. Thus, during angiotensin II infusion, ecSOD reduces hypertension, minimizes vascular superoxide production, and preserves endothelial function in resistance arterioles. We also identified novel compensatory mechanisms involving upregulation of copper chaperone for Cu/ZnSOD, increased Cu/ZnSOD activity, and decreased reduced nicotinamide-adenine dinucleotide phosphate oxidase activity in larger vessels. These compensatory mechanisms preserve large vessel function when ecSOD is absent in

  12. Oncogenic extracellular vesicles in brain tumour progression

    Directory of Open Access Journals (Sweden)

    Esterina eD'Asti

    2012-07-01

    Full Text Available The brain is a frequent site of neoplastic growth, including both primary and metastatic tumours. The clinical intractability of many brain tumours and their distinct biology are implicitly linked to the unique microenvironment of the central nervous system (CNS and cellular interactions within. Among the most intriguing forms of cellular interactions is that mediated by membrane-derived extracellular vesicles (EVs. Their biogenesis (vesiculation and uptake by recipient cells serves as a unique mechanism of intercellular trafficking of complex biological messages including the exchange of molecules that cannot be released through classical secretory pathways, or that are prone to extracellular degradation. Tumour cells produce EVs containing molecular effectors of several cancer-related processes such as growth, invasion, drug resistance, angiogenesis, and coagulopathy. Notably, tumour-derived EVs (oncosomes also contain oncogenic proteins, transcripts, DNA and microRNA (miR. Uptake of this material may change properties of the recipient cells and impact the tumour microenvironment. Examples of transformation-related molecules found in the cargo of tumour-derived EVs include the oncogenic epidermal growth factor receptor (EGFRvIII, tumour suppressors (PTEN and oncomirs (miR-520g. It is postulated that EVs circulating in blood or cerebrospinal fluid (CSF of brain tumour patients may be used to decipher molecular features (mutations of the underlying malignancy, reflect responses to therapy or molecular subtypes of primary brain tumours (e.g. glioma or medulloblastoma. It is possible that metastases to the brain may also emit EVs with clinically relevant oncogenic signatures. Thus EVs emerge as a novel and functionally important vehicle of intercellular communication that can mediate multiple biological effects. In addition, they provide a unique platform to develop molecular biomarkers in brain malignancies.

  13. Identification of a receptor for extracellular renalase.

    Directory of Open Access Journals (Sweden)

    Ling Wang

    Full Text Available An increased risk for developing essential hypertension, stroke and diabetes is associated with single nucleotide gene polymorphisms in renalase, a newly described secreted flavoprotein with oxidoreductase activity. Gene deletion causes hypertension, and aggravates acute ischemic kidney (AKI and cardiac injury. Independent of its intrinsic enzymatic activities, extracellular renalase activates MAPK signaling and prevents acute kidney injury (AKI in wild type (WT mice. Therefore, we sought to identity the receptor for extracellular renalase.RP-220 is a previously identified, 20 amino acids long renalase peptide that is devoid of any intrinsic enzymatic activity, but it is equally effective as full-length recombinant renalase at protecting against toxic and ischemic injury. Using biotin transfer studies with RP-220 in the human proximal tubular cell line HK-2 and protein identification by mass spectrometry, we identified PMCA4b as a renalase binding protein. This previously characterized plasma membrane ATPase is involved in cell signaling and cardiac hypertrophy. Co-immunoprecipitation and co-immunolocalization confirmed protein-protein interaction between endogenous renalase and PMCA4b. Down-regulation of endogenous PMCA4b expression by siRNA transfection, or inhibition of its enzymatic activity by the specific peptide inhibitor caloxin1b each abrogated RP-220 dependent MAPK signaling and cytoprotection. In control studies, these maneuvers had no effect on epidermal growth factor mediated signaling, confirming specificity of the interaction between PMCA4b and renalase.PMCA4b functions as a renalase receptor, and a key mediator of renalase dependent MAPK signaling.

  14. Ligand-specific regulation of the extracellular surface of a G-protein-coupled receptor

    Energy Technology Data Exchange (ETDEWEB)

    Bokoch, Michael P.; Zou, Yaozhong; Rasmussen, Søren G.F.; Liu, Corey W.; Nygaard, Rie; Rosenbaum, Daniel M.; Fung, Juan José; Choi, Hee-Jung; Thian, Foon Sun; Kobilka, Tong Sun; Puglisi, Joseph D.; Weis, William I.; Pardo, Leonardo; Prosser, R. Scott; Mueller, Luciano; Kobilka, Brian K. (Stanford-MED); (Toronto); (BMS); (UAB, Spain)

    2010-01-14

    G-protein-coupled receptors (GPCRs) are seven-transmembrane proteins that mediate most cellular responses to hormones and neurotransmitters. They are the largest group of therapeutic targets for a broad spectrum of diseases. Recent crystal structures of GPCRs have revealed structural conservation extending from the orthosteric ligand-binding site in the transmembrane core to the cytoplasmic G-protein-coupling domains. In contrast, the extracellular surface (ECS) of GPCRs is remarkably diverse and is therefore an ideal target for the discovery of subtype-selective drugs. However, little is known about the functional role of the ECS in receptor activation, or about conformational coupling of this surface to the native ligand-binding pocket. Here we use NMR spectroscopy to investigate ligand-specific conformational changes around a central structural feature in the ECS of the {beta}{sub 2} adrenergic receptor: a salt bridge linking extracellular loops 2 and 3. Small-molecule drugs that bind within the transmembrane core and exhibit different efficacies towards G-protein activation (agonist, neutral antagonist and inverse agonist) also stabilize distinct conformations of the ECS. We thereby demonstrate conformational coupling between the ECS and the orthosteric binding site, showing that drugs targeting this diverse surface could function as allosteric modulators with high subtype selectivity. Moreover, these studies provide a new insight into the dynamic behaviour of GPCRs not addressable by static, inactive-state crystal structures.

  15. El oficio

    OpenAIRE

    José Cabeza

    2013-01-01

    Es difícil escribir un manual de guión, sea confeso o enmascarado, es decir, tenga el nombre o el aspecto de un manual o sea una aproximación personal a cómo se escribe un guión. La dificultad reside en que no se puede enseñar a hacer un guión (aunque muchos lo pretenden), sino que se enseña un oficio. Y eso es lo que hace el autor de Golpe a golpe, versión a versión.

  16. El oficio

    Directory of Open Access Journals (Sweden)

    José Cabeza

    2013-09-01

    Full Text Available Es difícil escribir un manual de guión, sea confeso o enmascarado, es decir, tenga el nombre o el aspecto de un manual o sea una aproximación personal a cómo se escribe un guión. La dificultad reside en que no se puede enseñar a hacer un guión (aunque muchos lo pretenden, sino que se enseña un oficio. Y eso es lo que hace el autor de Golpe a golpe, versión a versión.

  17. Detection and Characterization of R Loop Structures.

    Science.gov (United States)

    Boque-Sastre, Raquel; Soler, Marta; Guil, Sonia

    2017-01-01

    R loops are special three stranded nucleic acid structures that comprise a nascent RNA hybridized with the DNA template strand, leaving a non-template DNA single-stranded. More specifically, R loops form in vivo as G-rich RNA transcripts invade the DNA duplex and anneal to the template strand to generate an RNA:DNA hybrid, leaving the non-template, G-rich DNA strand in a largely single-stranded conformation (Aguilera and Garcia-Muse, Mol Cell 46:115-124, 2012).DNA-RNA hybrids are a natural occurrence within eukaryotic cells, with levels of these hybrids increasing at sites with high transcriptional activity, such as during transcription initiation, repression, and elongation. RNA-DNA hybrids influence genomic instability, and growing evidence points to an important role for R loops in active gene expression regulation (Ginno et al., Mol Cell 45, 814-825, 2012; Sun et al., Science 340: 619-621, 2013; Bhatia et al., Nature 511, 362-365, 2014). Analysis of the occurrence of such structures is therefore of increasing relevance and herein we describe methods for the in vivo and in vitro identification and characterization of R loops in mammalian systems.R loops (DNA:RNA hybrids and the associated single-stranded DNA) have been traditionally associated with threats to genome integrity, making some regions of the genome more prone to DNA-damaging and mutagenic agents. Initially considered to be rare byproducts of transcription, over the last decade accumulating evidence has pointed to a new view in which R loops form more frequently than previously thought. The R loop field has become an increasingly expanded area of research, placing these structures as a major threat to genome stability but also as potential regulators of gene expression. Special interest has arisen as they have also been linked to a variety of diseases, including neurological disorders and cancer, positioning them as potential therapeutic targets [5].

  18. Extracellular loop 2 of the free Fatty Acid receptor 2 mediates allosterism of a phenylacetamide ago-allosteric modulator

    DEFF Research Database (Denmark)

    Smith, Nicola J; Ward, Richard J; Stoddart, Leigh A;

    2011-01-01

    Allosteric agonists are powerful tools for exploring the pharmacology of closely related G protein-coupled receptors that have nonselective endogenous ligands, such as the short chain fatty acids at free fatty acid receptors 2 and 3 (FFA2/GPR43 and FFA3/GPR41, respectively). We explored the molec...

  19. Reversed binding of a small molecule ligand in homologous chemokine receptors - differential role of extracellular loop 2

    DEFF Research Database (Denmark)

    Jensen, P C; Thiele, S; Steen, A;

    2012-01-01

    The majority of small molecule compounds targeting chemokine receptors share a similar pharmacophore with a centrally located aliphatic positive charge and flanking aromatic moieties. Here we describe a novel piperidine-based compound with structural similarity to previously described CCR8-specific...

  20. The Rho exchange factors Vav2 and Vav3 favor skin tumor initiation and promotion by engaging extracellular signaling loops.

    Directory of Open Access Journals (Sweden)

    Mauricio Menacho-Márquez

    2013-07-01

    Full Text Available The catalytic activity of GDP/GTP exchange factors (GEFs is considered critical to maintain the typically high activity of Rho GTPases found in cancer cells. However, the large number of them has made it difficult to pinpoint those playing proactive, nonredundant roles in tumors. In this work, we have investigated whether GEFs of the Vav subfamily exert such specific roles in skin cancer. Using genetically engineered mice, we show here that Vav2 and Vav3 favor cooperatively the initiation and promotion phases of skin tumors. Transcriptomal profiling and signaling experiments indicate such function is linked to the engagement of, and subsequent participation in, keratinocyte-based autocrine/paracrine programs that promote epidermal proliferation and recruitment of pro-inflammatory cells. This is a pathology-restricted mechanism because the loss of Vav proteins does not cause alterations in epidermal homeostasis. These results reveal a previously unknown Rho GEF-dependent pro-tumorigenic mechanism that influences the biology of cancer cells and their microenvironment. They also suggest that anti-Vav therapies may be of potential interest in skin tumor prevention and/or treatment.

  1. Extracellular polymeric substances act as transient media in extracellular electron transfer of Shewanella oneidensis MR-1

    DEFF Research Database (Denmark)

    Xiao, Yong; Zhang, Jingdong; Ulstrup, Jens

    without extracting EPS or cells collected from log stage or early-steady stage cultures with little EPS. Therefore, microbial cells are believed in contact directly with each other or electrode. Such attempt apparently ignored the role of EPS in microbial EET, even though many components of EPS......It is well known that microorganism is surrounded by extracellular polymeric substances (EPS) which include polysaccharides, proteins, glycoproteins, nucleic acids, phospholipids, and humic acids. However, previous studies on microbial extracellular electron transfer (EET) are conducted on cells......, such as DNA, humic acids and some proteins, are electrochemically active or semiconductive. Herein, we report experimental evidences of EPS role on EET for Shewanella oneidensis MR-1. Atomic force microscopy clearly showed that the cell surface was cleaned and few EPS could be observed on MR-1 after...

  2. Incorporation of Tenascin-C into the Extracellular Matrix by Periostin Underlies an Extracellular Meshwork Architecture*

    OpenAIRE

    Kii, Isao; Nishiyama, Takashi; Li, Minqi; Matsumoto, Ken-Ichi; Saito, Mitsuru; Amizuka, Norio; Kudo, Akira

    2009-01-01

    Extracellular matrix (ECM) underlies a complicated multicellular architecture that is subjected to significant forces from mechanical environment. Although various components of the ECM have been enumerated, mechanisms that evolve the sophisticated ECM architecture remain to be addressed. Here we show that periostin, a matricellular protein, promotes incorporation of tenascin-C into the ECM and organizes a meshwork architecture of the ECM. We found that both periostin null mice and tenascin-C...

  3. El Quijote

    Directory of Open Access Journals (Sweden)

    Jorge Ortega Torres

    1963-05-01

    Full Text Available Ha querido la Academia Colombiana conmemorar por medio de la presente festividad el tercer centenario de la muerte de Miguel de Cervantes Saavedra, y entre los números de su programa ha puesto el discurso que voy a pronunciar. El contrastará por su aridez con la otra pieza de esta velada, en la cual han corrido los primores de la forma a porfía con la belleza y sublimidad de las ideas. De esta suerte me quedará siempre la satisfacción de haber contribuído para el follaje de la corona ofrendada por la Academia a una de las primeras glorias de la literatura española y universal.

  4. El Nino.

    Science.gov (United States)

    Blueford, Joyce

    1988-01-01

    Information is presented regarding "El Nino," a warm ocean current which has a profound worldwide effect on ocean life and weather patterns. Suggestions are provided for teaching students about the current and other related topics. (CB)

  5. Open-loop versus closed-loop control of MEMS devices: choices and issues

    Science.gov (United States)

    Borovic, B.; Liu, A. Q.; Popa, D.; Cai, H.; Lewis, F. L.

    2005-10-01

    From a controls point of view, micro electromechanical systems (MEMS) can be driven in an open-loop and closed-loop fashion. Commonly, these devices are driven open-loop by applying simple input signals. If these input signals become more complex by being derived from the system dynamics, we call such control techniques pre-shaped open-loop driving. The ultimate step for improving precision and speed of response is the introduction of feedback, e.g. closed-loop control. Unlike macro mechanical systems, where the implementation of the feedback is relatively simple, in the MEMS case the feedback design is quite problematic, due to the limited availability of sensor data, the presence of sensor dynamics and noise, and the typically fast actuator dynamics. Furthermore, a performance comparison between open-loop and closed-loop control strategies has not been properly explored for MEMS devices. The purpose of this paper is to present experimental results obtained using both open- and closed-loop strategies and to address the comparative issues of driving and control for MEMS devices. An optical MEMS switching device is used for this study. Based on these experimental results, as well as computer simulations, we point out advantages and disadvantages of the different control strategies, address the problems that distinguish MEMS driving systems from their macro counterparts, and discuss criteria to choose a suitable control driving strategy.

  6. Attacking One-loop Multi-leg Feynman Integrals with the Loop-Tree Duality

    CERN Document Server

    Chachamis, Grigorios; Draggiotis, Petros; Rodrigo, German

    2016-01-01

    We discuss briefly the first numerical implementation of the Loop-Tree Duality (LTD) method. We apply the LTD method in order to calculate ultraviolet and infrared finite multi-leg one-loop Feynman integrals. We attack scalar and tensor integrals with up to six legs (hexagons). The LTD method shows an excellent performance independently of the number of external legs.

  7. Students' Understanding of Loops and Nested Loops in Computer Programming: An APOS Theory Perspective

    Science.gov (United States)

    Cetin, Ibrahim

    2015-01-01

    The purpose of this study is to explore students' understanding of loops and nested loops concepts. Sixty-three mechanical engineering students attending an introductory programming course participated in the study. APOS (Action, Process, Object, Schema) is a constructivist theory developed originally for mathematics education. This study is the…

  8. Infrared finitness and analyticity properties of the loop-loop scattering amplitudes in gauge theories

    CERN Document Server

    Meggiolaro, E

    2005-01-01

    We shall discuss about the infrared finitness and some analyticity properties of the loop-loop scattering amplitudes in gauge theories, when going from Minkowskian to Euclidean theory, and we shall see how they can be related to the still unsolved problem of the s-dependence of the hadron-hadron total cross-sections.

  9. Parallelization of While Loops in Nested Loop Programs for Shared-Memory Multiprocessor Systems

    NARCIS (Netherlands)

    Geuns, Stefan J.; Bekooij, Marco J.G.; Bijlsma, Tjerk; Corporaal, Henk

    2011-01-01

    Many applications contain loops with an undetermined number of iterations. These loops have to be parallelized in order to increase the throughput when executed on an embedded multiprocessor platform. This paper presents a method to automatically extract a parallel task graph based on function level

  10. El perro y el frisbee

    Directory of Open Access Journals (Sweden)

    Vasileios Madouros

    2012-12-01

    Full Text Available Este escrito analiza por qué el tipo de regulación financiera compleja desarrollado en las últimas décadas puede ser una respuesta subóptima a la creciente complejidad del sistema financiero. Los ejemplos de otras disciplinas muestran que la toma de decisiones en un entorno complejo se puede beneficiar con el uso de reglas prácticas simples o “heurísticas”. Una serie de experimentos empíricos para evaluar el desempeño relativo de las reglas simples y complejas en el entorno financiero muestra que los indicadores simples, como la relación de apalancamiento y las medidas de capital basadas en el mercado superan a las medidas más complejas ponderadas por el riesgo y a los modelos de múltiples indicadores en su capacidad para predecir quiebras bancarias. Un mensaje congruente de estos experimentos es que la complejidad de los modelos o los portafolios puede generar problemas de robustez. Presenta cinco lecciones de política a partir de estos resultados, relacionadas con el diseño de la regulación financiera y las posibles medidas encaminadas a reducir en forma más directa la complejidad del sistema financiero.

  11. El desacato

    OpenAIRE

    Romero-Pérez, Jorge Enrique

    2014-01-01

    Esta investigación analiza el artículo 307 del Código Penal relativo al desacato tipificado como una ofensa al honor del funcionario público y al cargo que desempeña. Consideramos que esta figura penal debe ser derogada por ser autoritaria y configuradora de privilegios para el personal del Estado.

  12. El basurero

    Directory of Open Access Journals (Sweden)

    Bradbury Ray

    1999-12-01

    Full Text Available Asi era su trabajo: se levantaba a las cinco de las fria y oscura mañanay se lavaba la cara con agua caliente si el aparato de calefaccion funcionaba y con agua fria si el aparato no funcionaba. Se afeitaba cuidadosamente, hablandole a su mujer en la cocina, que preparaba jamon y huevos o panqueques o lo que hubiera aquella mañana.

  13. Bootstrapping the Three-Loop Hexagon

    Energy Technology Data Exchange (ETDEWEB)

    Dixon, Lance J.; /CERN /SLAC; Drummond, James M.; /CERN /Annecy, LAPTH; Henn, Johannes M.; /Humboldt U., Berlin /Santa Barbara, KITP

    2011-11-08

    We consider the hexagonal Wilson loop dual to the six-point MHV amplitude in planar N = 4 super Yang-Mills theory. We apply constraints from the operator product expansion in the near-collinear limit to the symbol of the remainder function at three loops. Using these constraints, and assuming a natural ansatz for the symbol's entries, we determine the symbol up to just two undetermined constants. In the multi-Regge limit, both constants drop out from the symbol, enabling us to make a non-trivial confirmation of the BFKL prediction for the leading-log approximation. This result provides a strong consistency check of both our ansatz for the symbol and the duality between Wilson loops and MHV amplitudes. Furthermore, we predict the form of the full three-loop remainder function in the multi-Regge limit, beyond the leading-log approximation, up to a few constants representing terms not detected by the symbol. Our results confirm an all-loop prediction for the real part of the remainder function in multi-Regge 3 {yields} 3 scattering. In the multi-Regge limit, our result for the remainder function can be expressed entirely in terms of classical polylogarithms. For generic six-point kinematics other functions are required.

  14. Logical inference techniques for loop parallelization

    KAUST Repository

    Oancea, Cosmin E.

    2012-01-01

    This paper presents a fully automatic approach to loop parallelization that integrates the use of static and run-time analysis and thus overcomes many known difficulties such as nonlinear and indirect array indexing and complex control flow. Our hybrid analysis framework validates the parallelization transformation by verifying the independence of the loop\\'s memory references. To this end it represents array references using the USR (uniform set representation) language and expresses the independence condition as an equation, S = Ø, where S is a set expression representing array indexes. Using a language instead of an array-abstraction representation for S results in a smaller number of conservative approximations but exhibits a potentially-high runtime cost. To alleviate this cost we introduce a language translation F from the USR set-expression language to an equally rich language of predicates (F(S) ⇒ S = Ø). Loop parallelization is then validated using a novel logic inference algorithm that factorizes the obtained complex predicates (F(S)) into a sequence of sufficient-independence conditions that are evaluated first statically and, when needed, dynamically, in increasing order of their estimated complexities. We evaluate our automated solution on 26 benchmarks from PERFECTCLUB and SPEC suites and show that our approach is effective in parallelizing large, complex loops and obtains much better full program speedups than the Intel and IBM Fortran compilers. Copyright © 2012 ACM.

  15. Radio Pulsating Structures with Coronal Loop Contraction

    Science.gov (United States)

    Kallunki, J.; Pohjolainen, S.

    2012-10-01

    We present a multi-wavelength study of a solar eruption event on 20 July 2004, comprising observations in Hα, EUV, soft X-rays, and in radio waves with a wide frequency range. The analyzed data show both oscillatory patterns and shock wave signatures during the impulsive phase of the flare. At the same time, large-scale EUV loops located above the active region were observed to contract. Quasi-periodic pulsations with ˜ 10 and ˜ 15 s oscillation periods were detected both in microwave - millimeter waves and in decimeter - meter waves. Our calculations show that MHD oscillations in the large EUV loops - but not likely in the largest contracting loops - could have produced the observed periodicity in radio emission, by triggering periodic magnetic reconnection and accelerating particles. As the plasma emission in decimeter - meter waves traces the accelerated particle beams and the microwave emission shows a typical gyrosynchrotron flux spectrum (emission created by trapped electrons within the flare loop), we find that the particles responsible for the two different types of emission could have been accelerated in the same process. Radio imaging of the pulsed decimetric - metric emission and the shock-generated radio type II burst in the same wavelength range suggest a rather complex scenario for the emission processes and locations. The observed locations cannot be explained by the standard model of flare loops with an erupting plasmoid located above them, driving a shock wave at the CME front.

  16. Miniature loops in the solar corona

    CERN Document Server

    Barczynski, Krzysztof; Savage, Sabrina L

    2016-01-01

    Magnetic loops filled with hot plasma are the main building blocks of the solar corona. Usually they have lengths of the order of the barometric scale height in the corona that is 50 Mm. Previously it has been suggested that miniature versions of hot loops exist. These would have lengths of only 1 Mm barely protruding from the chromosphere and spanning across just one granule in the photosphere. Such short loops are well established at transition region temperatures (0.1 MK), and we investigate if such miniature loops also exist at coronal temperatures (>1 MK). We used extreme UV imaging (EUV) observations from the High-resolution Coronal Imager (Hi-C) at an unprecedented spatial resolution of 0.3" to 0.4". Together with EUV imaging and magnetogram data from the Solar Dynamics Observatory (SDO) and X-Ray Telescope (XRT) data from Hinode we investigated the spatial, temporal and thermal evolution of small loop-like structures in the solar corona above a plage region close to an active region and compared this ...

  17. Numerical simulation of a natural circulation loop

    Energy Technology Data Exchange (ETDEWEB)

    Verissimo, Gabriel L.; Moreira, Maria de Lourdes; Faccini, Jose Luiz H., E-mail: gabrielverissimo@poli.ufrj.b, E-mail: malu@ien.gov.b, E-mail: faccini@ien.gov.b [Instituto de Engenharia Nuclear (IEN/CNEN-RJ), Rio de Janeiro, RJ (Brazil)

    2011-07-01

    This work presents a numerical simulation of a natural circulation loop using computational fluid dynamics. The simulated loop is an experimental model in a reduced scale of 1:10 of a passive heat removal system typical of advanced PWR reactors. The loop is composed of a heating vessel containing 52 electric heaters, a vertical shell-tube heat exchanger and a column of expansion. The working fluid is distilled water. Initially it was created a tridimensional geometric model of the loop components. After that, it was generated a tridimensional mesh of finite elements in order to calculate the variables of the problem. The boundaries of the numerical simulation were the power of the electric resistances and the cooling flow in the secondary side of the heat exchanger. The initial conditions were the temperature, the pressure and the fluid velocity at the time just before the power has been switched on. The results of this simulation were compared with the experimental data, in terms of the evolution of the temperatures in different locations of the loop, and of the average natural circulation flow as a function of time for a given power. (author)

  18. Empirical potential simulations of interstitial dislocation loops in uranium dioxide

    Science.gov (United States)

    Le Prioux, Arno; Fossati, Paul; Maillard, Serge; Jourdan, Thomas; Maugis, Philippe

    2016-10-01

    Stoichiometric circular shaped interstitial dislocation loop energies are calculated in stoichiometric UO2 by empirical potential simulation. The Burgers vector directions studied are and . The main structural properties of each type of interstitial dislocation loop are determined, including stacking fault energy. Defect energies are compared and a maximum size for stable dislocation loops before transition to dislocation loops is given. A model of dislocation loop energy based on elasticity theory is then fitted on the basis of these simulation results.

  19. Utilization of chemical looping strategy in coal gasification processes

    Institute of Scientific and Technical Information of China (English)

    Liangshih Fan; Fanxing Li; Shwetha Ramkumar

    2008-01-01

    Three chemical looping gasification processes, i. e. Syngas Chemical Looping (SCL) process, Coal Direct Chemical Looping (CDCL) process, and Calcium Looping process (CLP), are being developed at the Ohio State University (OSU). These processes utilize simple reaction schemes to convert carbonaceous fuels into products such as hydrogen, electricity, and synthetic fuels through the transformation of a highly reactive, highly recyclable chemical intermediate. In this paper, these novel chemical looping gasification processes are described and their advantages and potential challenges for commercialization are discussed.

  20. On the origin of ion selectivity in the Cys-loop receptor family.

    Science.gov (United States)

    Sine, Steven M; Wang, Hai-Long; Hansen, Scott; Taylor, Palmer

    2010-01-01

    Agonist binding to Cys-loop receptors promotes a large transmembrane ion flux of several million cations or anions per second. To investigate structural bases for the dynamics (MD) simulations, X-ray crystallography, and single channel recording. MD simulations of the muscle nicotinic receptor, imbedded in a lipid bilayer with an applied transmembrane potential, reveal single cation translocation events during transient periods of channel hydration. During the simulation trajectory, cations paused for prolonged periods near several rings of anionic residues projecting from the lumen of the extracellular domain of the receptor, but subsequently the cation moved rapidly through the hydrophobic transmembrane region as the constituent alpha-helices exhibited back and forth rocking motions. Cocrystallization of acetylcholine binding protein with sulfate ions revealed coordination of five sulfates with residues from one of these charged rings; in cation-selective Cys-loop receptors this ring contains negatively charged residues, whereas in anion-selective receptors it contains positively charged residues. In the muscle nicotinic receptor, charge reversal of residues of this ring decreases unitary conductance by up to 80%. Thus in Cys-loop receptors, a series of charged rings along the ion translocation pathway concentrates hydrated ions relative to bulk solution, giving rise to charge selectivity, and then subtle motions of the hydrophobic transmembrane, coupled with transient periods of water filling, enable rapid ion flux.

  1. BPS Wilson loops and Bremsstrahlung function in ABJ(M): a two loop analysis

    Energy Technology Data Exchange (ETDEWEB)

    Bianchi, Marco S. [Institut für Physik, Humboldt-Universität zu Berlin,Newtonstraße 15, 12489 Berlin (Germany); Griguolo, Luca [Dipartimento di Fisica e Scienze della Terra, Università di Parmaand INFN Gruppo Collegato di Parma,Viale G.P. Usberti 7/A, 43100 Parma (Italy); Leoni, Matias [Physics Department, FCEyN-UBA & IFIBA-CONICETCiudad Universitaria, Pabellón I, 1428, Buenos Aires (Argentina); Penati, Silvia [Dipartimento di Fisica, Università di Milano-Bicoccaand INFN, Sezione di Milano-Bicocca,Piazza della Scienza 3, I-20126 Milano (Italy); Seminara, Domenico [Dipartimento di Fisica, Università di Firenzeand INFN Sezione di Firenze,via G. Sansone 1, 50019 Sesto Fiorentino (Italy)

    2014-06-19

    We study a family of circular BPS Wilson loops in N=6 super Chern-Simons-matter theories, generalizing the usual 1/2-BPS circle. The scalar and fermionic couplings depend on two deformation parameters and these operators can be considered as the ABJ(M) counterpart of the DGRT latitudes defined in N=4 SYM. We perform a complete two-loop analysis of their vacuum expectation value, discuss the appearance of framing-like phases and propose a general relation with cohomologically equivalent bosonic operators. We make an all-loop proposal for computing the Bremsstrahlung function associated to the 1/2-BPS cusp in terms of these generalized Wilson loops. When applied to our two-loop result it reproduces the known expression. Finally, we comment on the generalization of this proposal to the bosonic 1/6-BPS case.

  2. El arte y el decenio del ochenta

    OpenAIRE

    1988-01-01

    Afortunadamente, el arte tiene para cada época y para cada cuál su propio significado. El arte es tiempo sin tiempo. Mientras el momento represente un límite, como es el decenio del 80, posiblemente el hombre tienda a lo nostálgico, con visos de melancolía. El siglo XIX terminó envuelto en lo romántico y lo simbolista. Por ejemplo, el art nouveau interpretó la plasticidad, impregnó el espíritu de formas en las cuales el recurso ornamental tuvo como fin el recurso mismo y la armonía prioridad ...

  3. An Holomorphic Study Of Smarandache Automorphic and Cross Inverse Property Loops

    CERN Document Server

    Jaiyeola, Temitope Gbolahan

    2008-01-01

    By studying the holomorphic structure of automorphic inverse property quasigroups and loops[AIPQ and (AIPL)] and cross inverse property quasigroups and loops[CIPQ and (CIPL)], it is established that the holomorph of a loop is a Smarandache; AIPL, CIPL, K-loop, Bruck-loop or Kikkawa-loop if and only if its Smarandache automorphism group is trivial and the loop is itself is a Smarandache; AIPL, CIPL, K-loop, Bruck-loop or Kikkawa-loop.

  4. Automatic Loop Parallelization via Compiler Guided Refactoring

    DEFF Research Database (Denmark)

    Larsen, Per; Ladelsky, Razya; Lidman, Jacob

    For many parallel applications, performance relies not on instruction-level parallelism, but on loop-level parallelism. Unfortunately, many modern applications are written in ways that obstruct automatic loop parallelization. Since we cannot identify sufficient parallelization opportunities...... for these codes in a static, off-line compiler, we developed an interactive compilation feedback system that guides the programmer in iteratively modifying application source, thereby improving the compiler’s ability to generate loop-parallel code. We use this compilation system to modify two sequential...... benchmarks, finding that the code parallelized in this way runs up to 8.3 times faster on an octo-core Intel Xeon 5570 system and up to 12.5 times faster on a quad-core IBM POWER6 system. Benchmark performance varies significantly between the systems. This suggests that semi-automatic parallelization should...

  5. Parallelizing More Loops with Compiler Guided Refactoring

    DEFF Research Database (Denmark)

    Larsen, Per; Ladelsky, Razya; Lidman, Jacob

    2012-01-01

    The performance of many parallel applications relies not on instruction-level parallelism but on loop-level parallelism. Unfortunately, automatic parallelization of loops is a fragile process; many different obstacles affect or prevent it in practice. To address this predicament we developed...... an interactive compilation feedback system that guides programmers in iteratively modifying their application source code. This helps leverage the compiler’s ability to generate loop-parallel code. We employ our system to modify two sequential benchmarks dealing with image processing and edge detection......, resulting in scalable parallelized code that runs up to 8.3 times faster on an eightcore Intel Xeon 5570 system and up to 12.5 times faster on a quad-core IBM POWER6 system. Benchmark performance varies significantly between the systems. This suggests that semi-automatic parallelization should be combined...

  6. Logical inference techniques for loop parallelization

    DEFF Research Database (Denmark)

    Oancea, Cosmin Eugen; Rauchwerger, Lawrence

    2012-01-01

    This paper presents a fully automatic approach to loop parallelization that integrates the use of static and run-time analysis and thus overcomes many known difficulties such as nonlinear and indirect array indexing and complex control flow. Our hybrid analysis framework validates...... the parallelization transformation by verifying the independence of the loop's memory references. To this end it represents array references using the USR (uniform set representation) language and expresses the independence condition as an equation, S={}, where S is a set expression representing array indexes. Using...... ( F(S) => S = {} ). Loop parallelization is then validated using a novel logic inference algorithm that factorizes the obtained complex predicates F(S) into a sequence of sufficient-independence conditions that are evaluated first statically and, when needed, dynamically, in increasing order...

  7. Hybrid Models in Loop Quantum Cosmology

    CERN Document Server

    Navascués, B Elizaga; Marugán, G A Mena

    2016-01-01

    In the framework of Loop Quantum Cosmology, inhomogeneous models are usually quantized by means of a hybrid approach that combines loop quantization techniques with standard quantum field theory methods. This approach is based on a splitting of the phase space in a homogeneous sector, formed by global, zero-modes, and an inhomogeneous sector, formed by the remaining, infinite number of modes, that describe the local degrees of freedom. Then, the hybrid quantization is attained by adopting a loop representation for the homogeneous gravitational sector, while a Fock representation is used for the inhomogeneities. The zero-mode of the Hamiltonian constraint operator couples the homogeneous and inhomogeneous sectors. The hybrid approach, therefore, is expected to provide a suitable quantum theory in regimes where the main quantum effects of the geometry are those affecting the zero-modes, while the inhomogeneities, still being quantum, can be treated in a more conventional way. This hybrid strategy was first prop...

  8. Covariant diagrams for one-loop matching

    CERN Document Server

    Zhang, Zhengkang

    2016-01-01

    We present a diagrammatic formulation of recently-revived covariant functional approaches to one-loop matching from an ultraviolet (UV) theory to a low-energy effective field theory. Various terms following from a covariant derivative expansion (CDE) are represented by diagrams which, unlike conventional Feynman diagrams, involve gauge-covariant quantities and are thus dubbed "covariant diagrams." The use of covariant diagrams helps organize and simplify one-loop matching calculations, which we illustrate with examples. Of particular interest is the derivation of UV model-independent universal results, which reduce matching calculations of specific UV models to applications of master formulas. We show how such derivation can be done in a more concise manner than the previous literature, and discuss how additional structures that are not directly captured by existing universal results, including mixed heavy-light loops, open covariant derivatives, and mixed statistics, can be easily accounted for.

  9. Are loop quantum cosmos never singular?

    CERN Document Server

    Singh, Parampreet

    2009-01-01

    A unified treatment of all known types of singularities for flat, isotropic and homogeneous spacetimes in the framework of loop quantum cosmology (LQC) is presented. These include bangs, crunches and all future singularities. Using effective spacetime description we perform a model independent general analysis of the properties of curvature, behavior of geodesics and strength of singularities. For illustration purposes a phenomenological model based analysis is also performed. We show that all values of the scale factor at which a strong singularity may occur are excluded from the effective loop quantum spacetime. Further, if the evolution leads to either a vanishing or divergent scale factor then the loop quantum universe is asymptotically deSitter in that regime. We also show that there exist a class of sudden extremal events, which includes a recently discussed possibility, for which the curvature or its derivatives will always diverge. Such events however turn out to be harmless weak curvature singulariti...

  10. Is the world made of loops?

    CERN Document Server

    Afriat, Alexander

    2013-01-01

    In discussions of the Aharonov-Bohm effect, Healey and Lyre have attributed reality to loops $\\sigma_0$ (or hoops $[\\sigma_0]$), since the electromagnetic potential $A$ is unmeasurable and can therefore be transformed. I argue that $[A]=[A+d\\lambda]_{\\lambda}$ and the hoop $[\\sigma_0]$ are related by a meaningful duality, so that however one feels about $[A]$ (or any potential $A\\in[A]$), it is no worse than $[\\sigma_0]$ (or any loop $\\sigma_0\\in[\\sigma_0]$): no ontological firmness is gained by retreating to the loops, which are just as flimsy as the potentials. And one wonders how the unmeasurability of one entity can invest another with physical reality; would an eventual observation of $A$ dissolve $\\sigma_0$, consigning it to a realm of incorporeal mathematical abstractions?

  11. Closed-loop approach to thermodynamics

    CERN Document Server

    Goupil, C; Herbert, E; Benenti, G; D'Angelo, Y; Lecoeur, Ph

    2016-01-01

    We present the closed-loop approach to linear nonequilibrium thermodynamics considering a generic heat engine dissipatively connected to two temperature baths. The system is usually quite generally characterized by two parameters: the output power $P$ and the conversion efficiency $\\eta$, to which we add a third one, the working frequency $\\omega$. We establish that a detailed understanding of the effects of the dissipative coupling on the energy conversion process, necessitates the knowledge of only two quantities: the system's feedback factor $\\beta$ and its open-loop gain $A_{0}$, the product of which, $A_{0}\\beta$, characterizes the interplay between the efficiency, the output power and the operating rate of the system. The feedback loop approach thus provides a versatile and economical, hence efficient, tool for the study of any conversion engine operation for which a feedback factor may be defined as illustrated with a thermoelectric system.

  12. All Digital Phase-Locked Loop

    Directory of Open Access Journals (Sweden)

    Marijan Jurgo

    2013-05-01

    Full Text Available The paper reviews working principles of phase-locked loop and drawbacks of classical PLL structure in nanometric technologies. It is proposed to replace the classical structure by all-digital phase-locked loop structure. Authors described the main blocks of all-digital phase-locked loop (time to digital converter and digitally controlled oscillator and overviewed the quantization noise arising in these blocks as well as its minimization strategies. The calculated inverter delay in 65 nm CMOS technology was from 8.64 to 27.71 ps and time to digital converter quantization noise was from −104.33 to −82.17 dBc/Hz, with tres = 8.64–27.71 ps, TSVG = 143–333 ps, FREF = 20–60 MHz.Article in Lithuanian

  13. A Cosmological Sector in Loop Quantum Gravity

    CERN Document Server

    Koslowski, Tim A

    2007-01-01

    We use the method of embedding a subsystem (i.e. its observable algebra) into a larger quantum system to extract a cosmological sector from full Loop Quantum Gravity. The application of this method provides a setting for a systematic study of the interplay between diffeomorphism invariance and symmetry reduction. The non-triviality of this relation is shown by extracting a cosmological system that has configurations variables that are very similar to the ones of a super-selection sector of standard Loop Quantum Cosmology. The full operator algebra however turns out to be different from standard Loop Quantum Cosmology. The homogeneous isotropic sector of pure gravity turns out to be quantum mechanics on a circle. The dynamics of our system seems pathological at first sight, and we give both mathematical and physical reasons for this behavior and we explain a strategy to cure these pathologies.

  14. Closed-loop approach to thermodynamics

    Science.gov (United States)

    Goupil, C.; Ouerdane, H.; Herbert, E.; Benenti, G.; D'Angelo, Y.; Lecoeur, Ph.

    2016-09-01

    We present the closed-loop approach to linear nonequilibrium thermodynamics considering a generic heat engine dissipatively connected to two temperature baths. The system is usually quite generally characterized by two parameters: the output power P and the conversion efficiency η , to which we add a third one, the working frequency ω . We establish that a detailed understanding of the effects of the dissipative coupling on the energy conversion process requires only knowing two quantities: the system's feedback factor β and its open-loop gain A0, which product A0β characterizes the interplay between the efficiency, the output power, and the operating rate of the system. By raising the abstract hermodynamic analysis to a higher level, the feedback loop approach provides a versatile and economical, hence fairly efficient, tool for the study of any conversion engine operation for which a feedback factor can be defined.

  15. Covariant diagrams for one-loop matching

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Zhengkang [Michigan Univ., Ann Arbor, MI (United States). Michigan Center for Theoretical Physics; Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)

    2016-10-15

    We present a diagrammatic formulation of recently-revived covariant functional approaches to one-loop matching from an ultraviolet (UV) theory to a low-energy effective field theory. Various terms following from a covariant derivative expansion (CDE) are represented by diagrams which, unlike conventional Feynman diagrams, involve gaugecovariant quantities and are thus dubbed ''covariant diagrams.'' The use of covariant diagrams helps organize and simplify one-loop matching calculations, which we illustrate with examples. Of particular interest is the derivation of UV model-independent universal results, which reduce matching calculations of specific UV models to applications of master formulas. We show how such derivation can be done in a more concise manner than the previous literature, and discuss how additional structures that are not directly captured by existing universal results, including mixed heavy-light loops, open covariant derivatives, and mixed statistics, can be easily accounted for.

  16. A note on two-loop superloop

    CERN Document Server

    Belitsky, A V

    2012-01-01

    We explore the duality between supersymmetric Wilson loop on null polygonal contours in maximally supersymmetric Yang-Mills theory and next-to-maximal helicity violating (NMHV) scattering amplitudes. Earlier analyses demonstrated that the use of a dimensional regulator for ultraviolet divergences, induced due to presence of the cusps on the loop, yields anomalies that break both conformal symmetry and supersymmetry. At one-loop order, these are present only in Grassmann components localized in the vicinity of a single cusp and result in a universal function for any number of sites of the polygon that can be subtracted away in a systematic manner leaving a well-defined supersymmetric remainder dual to corresponding components of the superamplitude. The question remains though whether components which were free from the aforementioned supersymmetric anomaly at leading order of perturbation theory remain so once computed at higher orders. Presently we verify this fact by calculating a particular component of the...

  17. Automated one-loop calculations with GOSAM

    Energy Technology Data Exchange (ETDEWEB)

    Cullen, Gavin [Edinburgh Univ. (United Kingdom). School of Physics and Astronomy; Deutsches Elektronen-Synchrotron (DESY), Zeuthen (Germany); Greiner, Nicolas [Illinois Univ., Urbana-Champaign, IL (United States). Dept. of Physics; Max-Planck-Institut fuer Physik, Muenchen (Germany); Heinrich, Gudrun; Reiter, Thomas [Max-Planck-Institut fuer Physik, Muenchen (Germany); Luisoni, Gionata [Durham Univ. (United Kingdom). Inst. for Particle Physics Phenomenology; Mastrolia, Pierpaolo [Max-Planck-Institut fuer Physik, Muenchen (Germany); Padua Univ. (Italy). Dipt. di Fisica; Ossola, Giovanni [New York City Univ., NY (United States). New York City College of Technology; New York City Univ., NY (United States). The Graduate School and University Center; Tramontano, Francesco [European Organization for Nuclear Research (CERN), Geneva (Switzerland)

    2011-11-15

    We present the program package GoSam which is designed for the automated calculation of one-loop amplitudes for multi-particle processes in renormalisable quantum field theories. The amplitudes, which are generated in terms of Feynman diagrams, can be reduced using either D-dimensional integrand-level decomposition or tensor reduction. GoSam can be used to calculate one-loop QCD and/or electroweak corrections to Standard Model processes and offers the flexibility to link model files for theories Beyond the Standard Model. A standard interface to programs calculating real radiation is also implemented. We demonstrate the flexibility of the program by presenting examples of processes with up to six external legs attached to the loop. (orig.)

  18. Transition probability spaces in loop quantum gravity

    CERN Document Server

    Guo, Xiao-Kan

    2016-01-01

    We study the (generalized) transition probability spaces, in the sense of Mielnik and Cantoni, for spacetime quantum states in loop quantum gravity. First, we show that loop quantum gravity admits the structures of transition probability spaces. This is achieved by first checking such structures in covariant quantum mechanics, and then passing to spin foam models via the general boundary formulation. The transition probability space thus defined gives a simple way to reconstruct the Hilbert space of the canonical theory and the relevant quantum logical structure. Second, we show that the transition probability space and in particular the spin foam model are 2-categories. Then we discuss how to realize property transitions and causality in this categorical context in connection with presheaves on quantaloids and respectively causal categories. We conclude that transition probability spaces provide us with an alternative framework to understand various foundational questions of loop quantum gravity.

  19. Nonmedian Direct Products of Graphs with Loops

    CERN Document Server

    Krop, Elliot

    2011-01-01

    A \\emph{median graph} is a connected graph in which, for every three vertices, there exists a unique vertex $m$ lying on the geodesic between any two of the given vertices. We show that the only median graphs of the direct product $G\\times H$ are formed when $G=P_k$, for any integer $k\\geq 3$ and $H=P_l$, for any integer $l\\geq 2$, with a loop at an end vertex, where the direct product is taken over all connected graphs $G$ on at least three vertices or at least two vertices with at least one loop, and connected graphs $H$ with at least one loop.

  20. Illusory spirals and loops in crystal growth.

    Science.gov (United States)

    Shtukenberg, Alexander G; Zhu, Zina; An, Zhihua; Bhandari, Misha; Song, Pengcheng; Kahr, Bart; Ward, Michael D

    2013-10-22

    The theory of dislocation-controlled crystal growth identifies a continuous spiral step with an emergent lattice displacement on a crystal surface; a mechanistic corollary is that closely spaced, oppositely winding spirals merge to form concentric loops. In situ atomic force microscopy of step propagation on pathological L-cystine crystals did indeed show spirals and islands with step heights of one lattice displacement. We show by analysis of the rates of growth of smaller steps only one molecule high that the major morphological spirals and loops are actually consequences of the bunching of the smaller steps. The morphology of the bunched steps actually inverts the predictions of the theory: Spirals arise from pairs of dislocations, loops from single dislocations. Only through numerical simulation of the growth is it revealed how normal growth of anisotropic layers of molecules within the highly symmetrical crystals can conspire to create features in apparent violation of the classic theory.

  1. The blind loop syndrome in children.

    Science.gov (United States)

    Stewart, B A; Karrer, F M; Hall, R J; Lilly, J R

    1990-08-01

    Anatomical abnormalities of the small bowel that cause intestinal stagnation result in bacterial overgrowth and a blind loop syndrome (BLS). Bacterial breakdown of bile salts and deamination of protein lead to malabsorption, steatorrhea, and fat-soluble vitamin deficiencies. Four children developed BLS as a complication of necrotizing enterocolitis, jejunal atresia, gastroschisis, and biliary atresia. BLS was suggested by abdominal pain, feculent vomiting, steatorrhea, and hypoalbuminemia. Dilated, stagnant bowel loops were demonstrated in each instance by upper gastrointestinal contrast study. Positive intestinal bacterial aspirates were confirmatory. Antibiotic treatment in two patients improved symptomatology but all children ultimately required surgery. Surgical procedures consisted of blind loop resection, intestinal plication, and catheterization of the bilioenteric conduit. All patients are now asymptomatic but one child suffers from parenteral nutrition-related cirrhosis and another requires chronic antibiotic therapy.

  2. Quantum Monte Carlo with directed loops.

    Science.gov (United States)

    Syljuåsen, Olav F; Sandvik, Anders W

    2002-10-01

    We introduce the concept of directed loops in stochastic series expansion and path-integral quantum Monte Carlo methods. Using the detailed balance rules for directed loops, we show that it is possible to smoothly connect generally applicable simulation schemes (in which it is necessary to include backtracking processes in the loop construction) to more restricted loop algorithms that can be constructed only for a limited range of Hamiltonians (where backtracking can be avoided). The "algorithmic discontinuities" between general and special points (or regions) in parameter space can hence be eliminated. As a specific example, we consider the anisotropic S=1/2 Heisenberg antiferromagnet in an external magnetic field. We show that directed-loop simulations are very efficient for the full range of magnetic fields (zero to the saturation point) and anisotropies. In particular, for weak fields and anisotropies, the autocorrelations are significantly reduced relative to those of previous approaches. The back-tracking probability vanishes continuously as the isotropic Heisenberg point is approached. For the XY model, we show that back tracking can be avoided for all fields extending up to the saturation field. The method is hence particularly efficient in this case. We use directed-loop simulations to study the magnetization process in the two-dimensional Heisenberg model at very low temperatures. For LxL lattices with L up to 64, we utilize the step structure in the magnetization curve to extract gaps between different spin sectors. Finite-size scaling of the gaps gives an accurate estimate of the transverse susceptibility in the thermodynamic limit: chi( perpendicular )=0.0659+/-0.0002.

  3. Coronal Loops: Observations and Modeling of Confined Plasma

    Directory of Open Access Journals (Sweden)

    Fabio Reale

    2014-07-01

    Full Text Available Coronal loops are the building blocks of the X-ray bright solar corona. They owe their brightness to the dense confined plasma, and this review focuses on loops mostly as structures confining plasma. After a brief historical overview, the review is divided into two separate but not independent parts: the first illustrates the observational framework, the second reviews the theoretical knowledge. Quiescent loops and their confined plasma are considered and, therefore, topics such as loop oscillations and flaring loops (except for non-solar ones, which provide information on stellar loops are not specifically addressed here. The observational section discusses the classification, populations, and the morphology of coronal loops, its relationship with the magnetic field, and the loop stranded structure. The section continues with the thermal properties and diagnostics of the loop plasma, according to the classification into hot, warm, and cool loops. Then, temporal analyses of loops and the observations of plasma dynamics, hot and cool flows, and waves are illustrated. In the modeling section, some basics of loop physics are provided, supplying fundamental scaling laws and timescales, a useful tool for consultation. The concept of loop modeling is introduced and models are divided into those treating loops as monolithic and static, and those resolving loops into thin and dynamic strands. More specific discussions address modeling the loop fine structure and the plasma flowing along the loops. Special attention is devoted to the question of loop heating, with separate discussion of wave (AC and impulsive (DC heating. Large-scale models including atmosphere boxes and the magnetic field are also discussed. Finally, a brief discussion about stellar coronal loops is followed by highlights and open questions.

  4. V3 loop truncations in HIV-1 envelope impart resistance to coreceptor inhibitors and enhanced sensitivity to neutralizing antibodies.

    Directory of Open Access Journals (Sweden)

    Meg M Laakso

    2007-08-01

    Full Text Available The V1/V2 region and the V3 loop of the human immunodeficiency virus type I (HIV-1 envelope (Env protein are targets for neutralizing antibodies and also play an important functional role, with the V3 loop largely determining whether a virus uses CCR5 (R5, CXCR4 (X4, or either coreceptor (R5X4 to infect cells. While the sequence of V3 is variable, its length is highly conserved. Structural studies indicate that V3 length may be important for interactions with the extracellular loops of the coreceptor. Consistent with this view, genetic truncation of the V3 loop is typically associated with loss of Env function. We removed approximately one-half of the V3 loop from three different HIV-1 strains, and found that only the Env protein from the R5X4 strain R3A retained some fusion activity. Loss of V1/V2 (DeltaV1/V2 was well tolerated by this virus. Passaging of virus with the truncated V3 loop resulted in the derivation of a virus strain that replicated with wild-type kinetics. This virus, termed TA1, retained the V3 loop truncation and acquired several adaptive changes in gp120 and gp41. TA1 could use CCR5 but not CXCR4 to infect cells, and was extremely sensitive to neutralization by HIV-1 positive human sera, and by antibodies to the CD4 binding site and to CD4-induced epitopes in the bridging sheet region of gp120. In addition, TA1 was completely resistant to CCR5 inhibitors, and was more dependent upon the N-terminal domain of CCR5, a region of the receptor that is thought to contact the bridging sheet of gp120 and the base of the V3 loop, and whose conformation may not be greatly affected by CCR5 inhibitors. These studies suggest that the V3 loop protects HIV from neutralization by antibodies prevalent in infected humans, that CCR5 inhibitors likely act by disrupting interactions between the V3 loop and the coreceptor, and that altered use of CCR5 by HIV-1 associated with increased sensitivity to changes in the N-terminal domain can be linked

  5. El suicidio en el adolescencia

    OpenAIRE

    Gil Encinas, María

    2013-01-01

    Se intenta explicar en qué consiste el suicidio en la adolescencia. Para ello, es importante describir qué es el suicidio y qué factores participan en la conducta de suicidio, o dicho de otra forma, cuáles son las causas que llevan a un adolescente a suicidarse. También se aborda la prevención de la conducta suicida en adolescentes

  6. Quasi-periodic processes in the flare loop generated by sudden temperature enhancements at loop footpoints

    Science.gov (United States)

    Karlický, M.; Jelínek, P.

    2016-05-01

    Aims: During the impulsive flare phase, the plasma at the flare loop footpoints is rapidly heated by particle beams. In the present paper, we study processes that occur after this sudden heating in a two-dimensional magnetic loop. Methods: We adopt a 2D magnetohydrodynamic (MHD) model, in which we solve a full set of the ideal time-dependent MHD equations by means of the FLASH code, using the adaptive mesh refinement (AMR) method. Periods in the processes are estimated by the wavelet analysis technique. Results: We consider a model of the solar atmosphere with a symmetric magnetic loop. The length of this loop in the corona is approximately 21.5 Mm. At both loop footpoints, at the transition region, we initiate the Gaussian temperature (pressure) perturbation with the maximum temperature 14, 7, or 3.5 times higher than the unperturbed temperature. In the corona, the perturbations produce supersonic blast shocks with the Mach number of about 1.1, but well below Alfvén velocities. We consider cases with the same perturbations at both footpoints (symmetric case) and one with different perturbations (asymmetric case). In the symmetric case, the shocks move along both loop legs upwards to the top of the loop, where they interact and form a transient compressed region. Then they continue in their motion to the transition region at the opposite side of the loop, where they are reflected upwards, and so on. At the top of the loop, the shock appears periodically with the period of about 170 s. In the loop legs during this period, a double peak of the plasma parameters, which is connected with two arrivals of shocks, is detected: firstly, when the shock moves up and then when the shock, propagating from the opposite loop leg, moves down. Increasing the distance of the detection point in the loop leg from the top of the loop, the time interval between these shock arrivals increases. Thus, at these detection points, the processes with shorter periods can be detected. After

  7. El vitalhumanismo

    Directory of Open Access Journals (Sweden)

    Miguel Ángel Polo Santillán

    2011-05-01

    Full Text Available Darío Botero Uribe (1938-2010[1] fue profesor emérito de la Universidad de Colombia, cuenta con una vasta producción filosófica, unida por un proyecto original denominado Vitalismo Cósmico. Entre sus obras podemos mencionar: La voluntad de poder de Nietzsche (1992, con cuatro ediciones, Teoría social del derecho (1993, con cuatro ediciones, Manifiesto del pensamiento latinoamericano (1993, con cinco ediciones, El derecho a la utopía (1994, con cinco ediciones, Vida, ética y democracia (1995, con dos ediciones[2], Vitalismo Cósmico (2002, Discurso sobre el humanismo (2004, entre otros. Un rasgo de su actividad filosófica ha sido lograr constituir una escuela filosófica, que pretende mirar críticamente las filosofías actuales para poder formular una nueva propuesta, el Vitalismo Cósmico, desde el contexto latinoamericano. En este artículo queremos presentar sus principales tesis de la siguiente manera: la visión del hombre, la propuesta humanista y la ética vitalista que de ahí se genera. Finalmente, reflexionar sobre algunos aspectos problemáticos de su humanismo. [1] Conocí al maestro Darío Botero el año 2005, en el 1er. Encuentro Nacional por la Vida, que él organizó en Bogotá. Sin duda, él era expresión de su propia filosofía vitalista.   [2] Los datos sobre el número de ediciones han sido tomados del artículo de Damián Pachón (2008.

  8. 60-GHz CMOS phase-locked loops

    CERN Document Server

    Cheema, Hammad M; van Roermund, Arthur HM

    2010-01-01

    The promising high data rate wireless applications at millimeter wave frequencies in general and 60 GHz in particular have gained much attention in recent years. However, challenges related to circuit, layout and measurements during mm-wave CMOS IC design have to be overcome before they can become viable for mass market. ""60-GHz CMOS Phase-Locked Loops"" focusing on phase-locked loops for 60 GHz wireless transceivers elaborates these challenges and proposes solutions for them. The system level design to circuit level implementation of the complete PLL, along with separate implementations of i

  9. Wilson Loops in Noncommutative Yang Mills

    CERN Document Server

    Ishibashi, N; Kawai, H; Kitazawa, Y; Ishibashi, Nobuyuki; Iso, Satoshi; Kawai, Hikaru; Kitazawa, Yoshihisa

    2000-01-01

    We study the correlation functions of the Wilson loops in noncommutative Yang-Mills theory based upon its equivalence to twisted reduced models. We point out that there is a crossover at the noncommutativity scale. At large momentum scale, the Wilson loops in noncommmutative Yang-Mills represent extended objects. They coincide with those in ordinary Yang-Mills theory in low energy limit. The correlation functions on D-branes in IIB matrix model exhibit the identical crossover behavior. It is observed to be consistent with the supergravity description with running string coupling. We also explain that the results of Seiberg and Witten can be simply understood in our formalism.

  10. Spontaneous fluxoid formation in superconducting loops

    DEFF Research Database (Denmark)

    Monaco, R.; Mygind, Jesper; Rivers, R.

    2009-01-01

    a scaling relation on the quenching time τQ, as one would expect if the transition took place as fast as causality permits. However, the observed Zurek-Kibble scaling exponent σ=0.62±0.15 is two times larger than anticipated for large loops. Assuming Gaussian winding number densities we show......We report on the experimental verification of the Zurek-Kibble scenario in an isolated superconducting ring over a wide parameter range. The probability of creating a single flux quantum spontaneously during the fast normal-superconducting phase transition of a wide Nb loop clearly follows...

  11. Designing of optimal double loop networks

    Institute of Scientific and Technical Information of China (English)

    徐俊明

    1999-01-01

    The double loop network G(N; r, s) has N vertices and 2N directed edges. A natural question is how to choose r and s such that G(N; r, s) has diameter as short as possible for a given N. In 1993, Li, Xu and Zhang proposed a method of constructing double loop networks with the minimum diameter for the case of r=1.The method is developed to construct such networks that none of their minimum diameters can be reached at r=1.As a by-product, a flaw in an assertation by Esqu et al. is pointed out.

  12. Classical Loop Actions of Gauge Theories

    CERN Document Server

    Armand-Ugon, D; Griego, J R; Setaro, L; Armand-Ugon, Daniel; Gambini, Rodolfo; Griego, Jorge; Setaro, Leonardo

    1994-01-01

    Since the first attempts to quantize Gauge Theories and Gravity in the loop representation, the problem of the determination of the corresponding classical actions has been raised. Here we propose a general procedure to determine these actions and we explicitly apply it in the case of electromagnetism. Going to the lattice we show that the electromagnetic action in terms of loops is equivalent to the Wilson action, allowing to do Montecarlo calculations in a gauge invariant way. In the continuum these actions need to be regularized and they are the natural candidates to describe the theory in a ``confining phase''.

  13. Loop Optimization for Tensor Network Renormalization

    Science.gov (United States)

    Yang, Shuo; Gu, Zheng-Cheng; Wen, Xiao-Gang

    2017-03-01

    We introduce a tensor renormalization group scheme for coarse graining a two-dimensional tensor network that can be successfully applied to both classical and quantum systems on and off criticality. The key innovation in our scheme is to deform a 2D tensor network into small loops and then optimize the tensors on each loop. In this way, we remove short-range entanglement at each iteration step and significantly improve the accuracy and stability of the renormalization flow. We demonstrate our algorithm in the classical Ising model and a frustrated 2D quantum model.

  14. Tuning OpenACC loop execution

    KAUST Repository

    Feki, Saber

    2017-01-07

    The purpose of this chapter is to help OpenACC developer who is already familiar with the basic and essential directives to further improve his code performance by adding more descriptive clauses to OpenACC loop constructs. At the end of this chapter the reader will: • Have a better understanding of the purpose of the OpenACC loop construct and its associated clauses illustrated with use cases • Use the acquired knowledge in practice to further improve the performance of OpenACC accelerated codes

  15. On closed loop transient response system identification

    Directory of Open Access Journals (Sweden)

    Christer Dalen

    2016-10-01

    Full Text Available Some methods for transient closed loop step response system identification presented in the literature are reviewed. Interestingly some errors in a method published in the early 80's where propagated into a recently published method. These methods are reviewed and some improved methods are suggested and presented. The methods are compared against each other on some closed loop system examples, e.g. a well pipeline-riser severe-slugging flow regime example, using Monte Carlo simulations for comparison of the methods.

  16. Slipping magnetic reconnection in coronal loops.

    Science.gov (United States)

    Aulanier, Guillaume; Golub, Leon; Deluca, Edward E; Cirtain, Jonathan W; Kano, Ryouhei; Lundquist, Loraine L; Narukage, Noriyuki; Sakao, Taro; Weber, Mark A

    2007-12-07

    Magnetic reconnection of solar coronal loops is the main process that causes solar flares and possibly coronal heating. In the standard model, magnetic field lines break and reconnect instantaneously at places where the field mapping is discontinuous. However, another mode may operate where the magnetic field mapping is continuous but shows steep gradients: The field lines may slip across each other. Soft x-ray observations of fast bidirectional motions of coronal loops, observed by the Hinode spacecraft, support the existence of this slipping magnetic reconnection regime in the Sun's corona. This basic process should be considered when interpreting reconnection, both on the Sun and in laboratory-based plasma experiments.

  17. Single quark entropy and the Polyakov loop

    CERN Document Server

    Weber, Johannes Heinrich

    2016-01-01

    We study Quantum Chromodynamics (QCD) with 2+1 flavors with almost physical quark masses using the highly improved staggered quark action (HISQ). We calculate the Polyakov loop in a wide temperature range, obtain the free energy and the entropy of a single static quark and discuss the QCD crossover region in detail. We show that the entropy has a peak close to the chiral crossover and consider the consequences for the deconfinement aspects of the crossover phenomena. We study the renormalized Polyakov loop susceptibilities and place them into the context of the crossover. We also obtain a quantitative result for the onset of weak coupling behavior at high temperatures.

  18. Center-vortex loops with one selfintersection

    CERN Document Server

    Moosmann, Julain

    2008-01-01

    We investigate the 2D behavior of one-fold selfintersecting, topologically stabilized center-vortex loops in the confining phase of an SU(2) Yang-Mills theory. This coarse-graining is described by curve-shrinking evolution of center-vortex loops immersed in a flat 2D plane driving the renormalization-group flow of an effective `action'. We observe that the system evolves into a highly ordered state at finite noise level, and we speculate that this feature is connected with 2D planar high $T_c$ superconductivity in $FeAs$ systems.

  19. Non-standard loop quantum cosmology

    CERN Document Server

    Piechocki, Wlodzimierz

    2010-01-01

    We present results concerning the nature of the cosmological big bounce(BB) transition within the loop geometry underlying loop quantum cosmology (LQC). Our canonical quantization method is an alternative to the standard LQC. An evolution parameter we use has clear interpretation both at classical and quantum levels. The physical volume operator has discrete spectrum which is bounded from below. The minimum gap in the spectrum defines a quantum of the volume. The spectra of operators are parametrized by a free parameter to be determined.

  20. Minimal Superstrings and Loop Gas Models

    CERN Document Server

    Gaiotto, D; Takayanagi, T; Gaiotto, Davide; Rastelli, Leonardo; Takayanagi, Tadashi

    2005-01-01

    We reformulate the matrix models of minimal superstrings as loop gas models on random surfaces. In the continuum limit, this leads to the identification of minimal superstrings with certain bosonic string theories, to all orders in the genus expansion. RR vertex operators arise as operators in a Z_2 twisted sector of the matter CFT. We show how the loop gas model implements the sum over spin structures expected from the continuum RNS formulation. Open string boundary conditions are also more transparent in this language.

  1. Reverse Loop subdivision with sharp features

    Institute of Scientific and Technical Information of China (English)

    Zhao Mingxi; Ma Lizhuang; Mao Zhihong; Wu Xiaomao

    2006-01-01

    In this paper we introduce a new reverse Loop subdivision method. In contrast to current wavelets based Loop subdivision scheme, our method applies the same rules to both regular and extraordinary vertices and reconstructs the sharp features easily. Furthermore, our method runs faster because it does not need analysis and synthesis procedural. Our main goal is the design of a reverse subdivision method that can reconstruct the coarser mesh from a finer subdivision surface with sharp features for multiresolution representation. The proposed method only needs a little memory storage and brings little error, and it is easy to implement.

  2. Perturbative loop corrections and nonlocal gravity

    CERN Document Server

    Maggiore, Michele

    2016-01-01

    Nonlocal gravity has been shown to provide a phenomenologically viable infrared modification of GR. A natural question is whether the required nonlocality can emerge from perturbative quantum loop corrections due to light particles. We show that this is not the case. For the value of the mass scale of the non-local models required by cosmology, the perturbative form factors obtained from the loop corrections, in the present cosmological epoch, are in the regime where they are local. The mechanism behind the generation of the required nonlocality must be more complex, possibly related to strong infrared effects and non-perturbative mass generation for the conformal mode.

  3. Loop Quantum Cosmology: Anisotropy and singularity resolution

    CERN Document Server

    Corichi, Alejandro; Montoya, Edison

    2012-01-01

    In this contribution we consider the issue of singularity resolution within loop quantum cosmology (LQC) for different homogeneous models. We present results of numerical evolutions of effective equations for both isotropic as well as anisotropic cosmologies, with and without spatial curvature. To address the issue of singularity resolution we examine the time evolution of geometrical and curvature invariants that yield information about the semiclassical spacetime geometry. We discuss generic behavior found for a variety of initial conditions. Finally, we show that the modifications which come from Loop Quantum Cosmology imply a non-chaotic effective behavior in the vacuum Bianchi IX model.

  4. Loop Optimization for Tensor Network Renormalization.

    Science.gov (United States)

    Yang, Shuo; Gu, Zheng-Cheng; Wen, Xiao-Gang

    2017-03-17

    We introduce a tensor renormalization group scheme for coarse graining a two-dimensional tensor network that can be successfully applied to both classical and quantum systems on and off criticality. The key innovation in our scheme is to deform a 2D tensor network into small loops and then optimize the tensors on each loop. In this way, we remove short-range entanglement at each iteration step and significantly improve the accuracy and stability of the renormalization flow. We demonstrate our algorithm in the classical Ising model and a frustrated 2D quantum model.

  5. Effective constraints of loop quantum gravity

    CERN Document Server

    Bojowald, M; Kagan, M; Skirzewski, A; Bojowald, Martin; Hernandez, Hector; Kagan, Mikhail; Skirzewski, Aureliano

    2006-01-01

    Within a perturbative cosmological regime of loop quantum gravity corrections to effective constraints are computed. This takes into account all inhomogeneous degrees of freedom relevant for scalar metric modes around flat space and results in explicit expressions for modified coefficients and of higher order terms. It also illustrates the role of different scales determining the relative magnitude of corrections. Our results demonstrate that loop quantum gravity has the correct classical limit, at least in its sector of cosmological perturbations around flat space, in the sense of perturbative effective theory.

  6. Loops in canonical RNA pseudoknot structures

    CERN Document Server

    Nebel, Markus E; Wang, Rita R

    2009-01-01

    In this paper we compute the limit distributions of the numbers of hairpin-loops, interior-loops and bulges in k-noncrossing RNA structures. The latter are coarse grained RNA structures allowing for cross-serial interactions, subject to the constraint that there are at most k-1 mutually crossing arcs in the diagram representation of the molecule. We prove central limit theorems by means of studying the corresponding bivariate generating functions. These generating functions are obtained by symbolic inflation of Ik5-shapes.

  7. A True Open-Loop Synchronization Technique

    DEFF Research Database (Denmark)

    Golestan, Saeed; Vidal, Ana; Yepes, Alejandro G.

    2016-01-01

    to worsen in the presence of frequency drifts. To deal with this problem, two approaches are often recommended in the literature: Adapting OLS techniques to grid frequency variations by feeding back the frequency estimated by them or using the frequency estimated by a secondary frequency detector...... in a parallel manner. In the presence of the frequency feedback loop, nevertheless, the OLS technique may not be truly open-loop, which makes a deep study of stability necessary. Using the secondary frequency detector, on the other hand, increases the computational effort and implementation complexity. Another...

  8. Harold el patoso, el pavoroso

    Directory of Open Access Journals (Sweden)

    A. JAVIER IZQUIERDO MARTÍN

    2007-01-01

    Full Text Available Al hilo de la reciente publicación de la traducción castellana de los Estudios en etnometodología, la obra clásica del radicalismo sociológico de los sesenta escrita por el profesor estadounidense Harold Garfinkel, el presente trabajo pretende ofrecer a la comunidad académica de habla castellana un ensayo de evaluaciónretrospectivo-prospectiva de la revolución etnometodológica en las ciencias sociales en clave netamente hispánica. A tal fin disponemos un conjunto original de elementos temáticos y pistas contextuales con la intención expresa de incitar al lector a leer a Garfinkel desde una óptica original: (1 la segunda venidadel brujo de Los Ángeles cuarenta años más tarde (Ethnomethodology's Program, 2002; (2 el caso Agnes contra el caso Castaneda; (3 el tratado sociológico implícito en el Quijote; (y 4 la genealogía heideggeriana del ramalazo videogámico de la etnometodología garfinkeliana.

  9. The extracellular matrix in breast cancer.

    Science.gov (United States)

    Insua-Rodríguez, Jacob; Oskarsson, Thordur

    2016-02-01

    The extracellular matrix (ECM) is increasingly recognized as an important regulator in breast cancer. ECM in breast cancer development features numerous changes in composition and organization when compared to the mammary gland under homeostasis. Matrix proteins that are induced in breast cancer include fibrillar collagens, fibronectin, specific laminins and proteoglycans as well as matricellular proteins. Growing evidence suggests that many of these induced ECM proteins play a major functional role in breast cancer progression and metastasis. A number of the induced ECM proteins have moreover been shown to be essential components of metastatic niches, promoting stem/progenitor signaling pathways and metastatic growth. ECM remodeling enzymes are also markedly increased, leading to major changes in the matrix structure and biomechanical properties. Importantly, several ECM components and ECM remodeling enzymes are specifically induced in breast cancer or during tissue regeneration while healthy tissues under homeostasis express exceedingly low levels. This may indicate that ECM and ECM-associated functions may represent promising drug targets against breast cancer, providing important specificity that could be utilized when developing therapies. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. PREPARATION AND PROPERTIES OF EXTRACELLULAR BIOPOLYMER FLOCCULANT

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The biopolymer flocculant (named PS-2) producing by Pseudomonas fluorescens was investigated. The PS-2 had high efficiency with small dosage, when dealing with kaolin suspension, formed larger floc, with big sedimentation rate, over a wide range of temperatures. Distributing of flocculating activity test showed that the biopolymer flocculant was an extracellular product. The composition analysis of purified biopolymer flocculant showed that it composed mainly of polysaccharide and nucleic acid. The content of polysaccharide was 86.7%, which determined by using phenol-vitriol method, and the content of nucleic acid was 7.8%, which determined by UV absorption method. The biopolymer flocculant as a powder form showed much better stability than that as a supernatant. The character of biopolymer flocculant was stable even it was heated to 100℃ when it in acidic condition. The optimal conditions to flocculate kaolin suspension were as follows: pH 8~12, flocculant dosage 1mL/L, and Ca2+ as the optimal cation.

  11. Bacterial Extracellular Polysaccharides Involved in Biofilm Formation

    Directory of Open Access Journals (Sweden)

    Elena P. Ivanova

    2009-07-01

    Full Text Available Extracellular polymeric substances (EPS produced by microorganisms are a complex mixture of biopolymers primarily consisting of polysaccharides, as well as proteins, nucleic acids, lipids and humic substances. EPS make up the intercellular space of microbial aggregates and form the structure and architecture of the biofilm matrix. The key functions of EPS comprise the mediation of the initial attachment of cells to different substrata and protection against environmental stress and dehydration. The aim of this review is to present a summary of the current status of the research into the role of EPS in bacterial attachment followed by biofilm formation. The latter has a profound impact on an array of biomedical, biotechnology and industrial fields including pharmaceutical and surgical applications, food engineering, bioremediation and biohydrometallurgy. The diverse structural variations of EPS produced by bacteria of different taxonomic lineages, together with examples of biotechnological applications, are discussed. Finally, a range of novel techniques that can be used in studies involving biofilm-specific polysaccharides is discussed.

  12. PREPARATION AND PROPERTIES OF EXTRACELLULAR BIOPOLYMER FLOCCULANT

    Institute of Scientific and Technical Information of China (English)

    LI Chunxiang; LIU Binbin; XIONG Jinshui; YAN Jingchun

    2007-01-01

    The biopolymer flocculant (named PS-2) producing by Pseudomonas fluorescens was investigated. The PS-2 had high efficiency with small dosage, when dealing with kaolin suspension,formed larger floc, with big sedimentation rate, over a wide range of temperatures. Distributing of flocculating activity test showed that the biopolymer flocculant was an extracellular product. The composition analysis of purified biopolymer flocculant showed that it composed mainly of polysaccharide and nucleic acid. The content of polysaccharide was 86.7%, which determined by using phenol-vitriol method, and the content of nucleic acid was 7.8%, which determined by UV absorption method. The biopolymer flocculant as a powder form showed much better stability than that as a supernatant. The character of biopolymer flocculant was stable even it was heated to 100 ℃ when it in acidic condition. The optimal conditions to flocculate kaolin suspension were as follows:pH 8~12, flocculant dosage 1mL/L, and Ca2+ as the optimal cation.

  13. Getting to know the extracellular vesicle glycome.

    Science.gov (United States)

    Gerlach, Jared Q; Griffin, Matthew D

    2016-04-01

    Extracellular vesicles (EVs) are a diverse population of complex biological particles with diameters ranging from approximately 20 to 1000 nm. Tremendous interest in EVs has been generated following a number of recent, high-profile reports describing their potential utility in diagnostic, prognostic, drug delivery, and therapeutic roles. Subpopulations, such as exosomes, are now known to directly participate in cell-cell communication and direct material transfer. Glycomics, the 'omic' portion of the glycobiology field, has only begun to catalog the surface oligosaccharide and polysaccharide structures and also the carbohydrate-binding proteins found on and inside EVs. The EV glycome undoubtedly contains vital clues essential to better understanding the function, biogenesis, release and transfer of vesicles, however getting at this information is technically challenging and made even more so because of the small physical size of the vesicles and the typically minute yield from physiological-scale biological samples. Vesicle micro-heterogeneity which may be related to specific vesicle origins and functions presents a further challenge. A number of primary studies carried out over the past decade have turned up specific and valuable clues regarding the composition and roles of glycan structures and also glycan binding proteins involved EV biogenesis and transfer. This review explores some of the major EV glycobiological research carried out to date and discusses the potential implications of these findings across the life sciences.

  14. Extracellular Vesicles: potential roles in Regenerative Medicine

    Directory of Open Access Journals (Sweden)

    Olivier G de Jong

    2014-12-01

    Full Text Available Extracellular vesicles (EV consist of exosomes, which are released upon fusion of the multivesicular body with the cell membrane, and microvesicles, which are released directly from the cell membrane. EV can mediate cell-cell communication and are involved in many processes, including immune signaling, angiogenesis, stress response, senescence, proliferation, and cell differentiation. The vast amount of processes that EV are involved in and the versatility of manner in which they can influence the behavior of recipient cells make EV an interesting source for both therapeutic and diagnostic applications. Successes in the fields of tumor biology and immunology sparked the exploration of the potential of EV in the field of regenerative medicine. Indeed, EV are involved in restoring tissue and organ damage, and may partially explain the paracrine effects observed in stem cell based therapeutic approaches. The function and content of EV may also harbor information that can be used in tissue engineering, in which paracrine signaling is employed to modulate cell recruitment, differentiation, and proliferation. In this review, we discuss the function and role of EV in regenerative medicine and elaborate on potential applications in tissue engineering.

  15. Tumorigenic Potential of Extracellular Matrix Metalloproteinase Inducer

    Science.gov (United States)

    Zucker, Stanley; Hymowitz, Michelle; Rollo, Ellen E.; Mann, Richard; Conner, Cathleen E.; Cao, Jian; Foda, Hussein D.; Tompkins, David C.; Toole, Bryan P.

    2001-01-01

    Extracellular matrix metalloproteinase inducer (EMMPRIN), a glycoprotein present on the cancer cell plasma membrane, enhances fibroblast synthesis of matrix metalloproteinases (MMPs). The demonstration that peritumoral fibroblasts synthesize most of the MMPs in human tumors rather than the cancer cells themselves has ignited interest in the role of EMMPRIN in tumor dissemination. In this report we have demonstrated a role for EMMPRIN in cancer progression. Human MDA-MB-436 breast cancer cells, which are tumorigenic but slow growing in vivo, were transfected with EMMPRIN cDNA and injected orthotopically into mammary tissue of female NCr nu/nu mice. Green fluorescent protein was used to visualize metastases. In three experiments, breast cancer cell clones transfected with EMMPRIN cDNA were considerably more tumorigenic and invasive than plasmid-transfected cancer cells. Increased gelatinase A and gelatinase B expression (demonstrated by in situ hybridization and gelatin substrate zymography) was demonstrated in EMMPRIN-enhanced tumors. In contrast to de novo breast cancers in humans, human tumors transplanted into mice elicited minimal stromal or inflammatory cell reactions. Based on these experimental studies and our previous demonstration that EMMPRIN is prominently displayed in human cancer tissue, we propose that EMMPRIN plays an important role in cancer progression by increasing synthesis of MMPs. PMID:11395366

  16. Analysis of extracellular RNA in cerebrospinal fluid

    Science.gov (United States)

    Saugstad, Julie A.; Lusardi, Theresa A.; Van Keuren-Jensen, Kendall R.; Phillips, Jay I.; Lind, Babett; Harrington, Christina A.; McFarland, Trevor J.; Courtright, Amanda L.; Reiman, Rebecca A.; Yeri, Ashish S.; Kalani, M. Yashar S.; Adelson, P. David; Arango, Jorge; Nolan, John P.; Duggan, Erika; Messer, Karen; Akers, Johnny C.; Galasko, Douglas R.; Quinn, Joseph F.; Carter, Bob S.; Hochberg, Fred H.

    2017-01-01

    ABSTRACT We examined the extracellular vesicle (EV) and RNA composition of pooled normal cerebrospinal fluid (CSF) samples and CSF from five major neurological disorders: Alzheimer’s disease (AD), Parkinson’s disease (PD), low-grade glioma (LGG), glioblastoma multiforme (GBM), and subarachnoid haemorrhage (SAH), representing neurodegenerative disease, cancer, and severe acute brain injury. We evaluated: (I) size and quantity of EVs by nanoparticle tracking analysis (NTA) and vesicle flow cytometry (VFC), (II) RNA yield and purity using four RNA isolation kits, (III) replication of RNA yields within and between laboratories, and (IV) composition of total and EV RNAs by reverse transcription–quantitative polymerase chain reaction (RT-qPCR) and RNA sequencing (RNASeq). The CSF contained ~106 EVs/μL by NTA and VFC. Brain tumour and SAH CSF contained more EVs and RNA relative to normal, AD, and PD. RT-qPCR and RNASeq identified disease-related populations of microRNAs and messenger RNAs (mRNAs) relative to normal CSF, in both total and EV fractions. This work presents relevant measures selected to inform the design of subsequent replicative CSF studies. The range of neurological diseases highlights variations in total and EV RNA content due to disease or collection site, revealing critical considerations guiding the selection of appropriate approaches and controls for CSF studies. PMID:28717417

  17. EXTRACELLULAR POLYSACCHARIDES OF POTATO RING ROT PATHOGEN

    Directory of Open Access Journals (Sweden)

    Shafikova Т.N.

    2006-03-01

    Full Text Available Many bacteria, including phytopathogenic ones produce extracellular polysaccharides or exopolysaccharides which are universal molecules. Causal agent of potato ring rot, Clavibacter michiganensis subspecies sepedonicus, secretes exopolysaccharides which role in pathogenesis is poorly investigated. The aim of our research is to ascertain the composition and structure of Clavibacter michiganensis subspecies sepedonicus exopolysaccharides. Exopolysaccharides of Clavibacter michiganensis subspecies sepedonicus are determined to consist of 4-6 anionic and neutral components which have molecular weights from 700 kDa. Glucose is a major monomer of polysaccharides and arabinose, rhamnose and mannose are minor monomers. Glucose is present in α-Dglucopyranose and β-D-glucopyranose configurations. Calcium is determined to be a component of exopolysaccharides. Components of exopolysaccharides of potato ring rot pathogen are probably capableto associate via calcium ions and other ionic interactions that may result in a change of their physiological activity. Further studies of Clavibacter michiganensis subspecies sepedonicus exopolysaccharides composition and structure can serve a base for the synthesis of their chemical analogues with elicitor action.

  18. Towards traceable size determination of extracellular vesicles

    Directory of Open Access Journals (Sweden)

    Zoltán Varga

    2014-02-01

    Full Text Available Background: Extracellular vesicles (EVs have clinical importance due to their roles in a wide range of biological processes. The detection and characterization of EVs are challenging because of their small size, low refractive index, and heterogeneity. Methods: In this manuscript, the size distribution of an erythrocyte-derived EV sample is determined using state-of-the-art techniques such as nanoparticle tracking analysis, resistive pulse sensing, and electron microscopy, and novel techniques in the field, such as small-angle X-ray scattering (SAXS and size exclusion chromatography coupled with dynamic light scattering detection. Results: The mode values of the size distributions of the studied erythrocyte EVs reported by the different methods show only small deviations around 130 nm, but there are differences in the widths of the size distributions. Conclusion: SAXS is a promising technique with respect to traceability, as this technique was already applied for traceable size determination of solid nanoparticles in suspension. To reach the traceable measurement of EVs, monodisperse and highly concentrated samples are required.

  19. Extracellular Vesicles and Autophagy in Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Tianyang Gao

    2016-01-01

    Full Text Available Osteoarthritis (OA is a type of chronic joint disease that is characterized by the degeneration and loss of articular cartilage and hyperplasia of the synovium and subchondral bone. There is reasonable knowledge about articular cartilage physiology, biochemistry, and chondrocyte metabolism. However, the etiology and pathogenesis of OA remain unclear and need urgent clarification to guide the early diagnosis and treatment of OA. Extracellular vesicles (EVs are small membrane-linking particles that are released from cells. In recent decades, several special biological properties have been found in EV, especially in terms of cartilage. Autophagy plays a critical role in the regulation of cellular homeostasis. Likewise, more and more research has gradually focused on the effect of autophagy on chondrocyte proliferation and function in OA. The synthesis and release of EV are closely associated with autophagy. At the same time, both EV and autophagy play a role in OA development. Based on the mechanism of EV and autophagy in OA development, EV may be beneficial in the early diagnosis of OA; on the other hand, the combination of EV and autophagy-related regulatory drugs may provide insight into possible OA therapeutic strategies.

  20. Relevance of extracellular DNA in rhizosphere

    Science.gov (United States)

    Pietramellara, Giacomo; Ascher, Judith; Baraniya, Divyashri; Arfaioli, Paola; Ceccherini, Maria Teresa; Hawes, Martha

    2013-04-01

    One of the most promising areas for future development is the manipulation of the rhizosphere to produce sustainable and efficient agriculture production systems. Using Omics approaches, to define the distinctive features of eDNA systems and structures, will facilitate progress in rhizo-enforcement and biocontrol studies. The relevance of these studies results clear when we consider the plethora of ecological functions in which eDNA is involved. This fraction can be actively extruded by living cells or discharged during cellular lysis and may exert a key role in the stability and variability of the soil bacterial genome, resulting also a source of nitrogen and phosphorus for plants due to the root's capacity to directly uptake short DNA fragments. The adhesive properties of the DNA molecule confer to eDNA the capacity to inhibit or kill pathogenic bacteria by cation limitation induction, and to facilitate formation of biofilm and extracellular traps (ETs), that may protect microorganisms inhabiting biofilm and plant roots against pathogens and allelopathic substances. The ETs are actively extruded by root border cells when they are dispersed in the rhizosphere, conferring to plants the capacity to extend an endogenous pathogen defence system outside the organism. Moreover, eDNA could be involved in rhizoremediation in heavy metal polluted soil acting as a bioflotation reagent.

  1. Engineering hydrogels as extracellular matrix mimics.

    Science.gov (United States)

    Geckil, Hikmet; Xu, Feng; Zhang, Xiaohui; Moon, SangJun; Demirci, Utkan

    2010-04-01

    Extracellular matrix (ECM) is a complex cellular environment consisting of proteins, proteoglycans, and other soluble molecules. ECM provides structural support to mammalian cells and a regulatory milieu with a variety of important cell functions, including assembling cells into various tissues and organs, regulating growth and cell-cell communication. Developing a tailored in vitro cell culture environment that mimics the intricate and organized nanoscale meshwork of native ECM is desirable. Recent studies have shown the potential of hydrogels to mimic native ECM. Such an engineered native-like ECM is more likely to provide cells with rational cues for diagnostic and therapeutic studies. The research for novel biomaterials has led to an extension of the scope and techniques used to fabricate biomimetic hydrogel scaffolds for tissue engineering and regenerative medicine applications. In this article, we detail the progress of the current state-of-the-art engineering methods to create cell-encapsulating hydrogel tissue constructs as well as their applications in in vitro models in biomedicine.

  2. Overview of Extracellular Microvesicles in Drug Metabolism

    Science.gov (United States)

    Conde-Vancells, Javier; Gonzalez, Esperanza; Lu, Shelly C.; Mato, Jose M.; Falcon-Perez, Juan M.

    2010-01-01

    Importance of the field Liver is the major body reservoir for enzymes involved in the metabolism of endogenous and xenobiotic compounds. Recently, it has been shown that hepatocytes release exosome-like vesicles to the extracellular medium, and the proteomic characterization of these hepatocyte-secreted exosomes has revealed the presence of several of these enzymes on them. Areas covered in this review A systematic bibliographic search focus on two related aspects: 1) xenobiotic-metabolizing enzymes that have been detected in microvesicles, and 2) microvesicles which are in the blood stream or secreted by cell-types with clear interactions with this fluid. What the reader will gain A discussion of these hepatocyte-secreted vesicles along with others microvesicles as enzymatic carriers in the context of extrahepatic drug-metabolizing systems. Take home message The contribution of many tissues including the liver to the microvesicles plasma population is supported by several reports. On the other hand, many enzymes involved in the metabolism of drugs have been detected in microvesicles. Together, these observations argue positively through a role of hepatic-microvesicles in spreading the liver metabolizing activities through the body contributing in this manner to extrahepatic drug metabolism systems what could be relevant for body homeostasis and pharmaceutical interests. PMID:20192903

  3. Extracellular ice phase transitions in insects.

    Science.gov (United States)

    Hawes, T C

    2014-01-01

    At temperatures below their temperature of crystallization (Tc), the extracellular body fluids of insects undergo a phase transition from liquid to solid. Insects that survive the transition to equilibrium (complete freezing of the body fluids) are designated as freeze tolerant. Although this phenomenon has been reported and described in many Insecta, current nomenclature and theory does not clearly delineate between the process of transition (freezing) and the final solid phase itself (the frozen state). Thus freeze tolerant insects are currently, by convention, described in terms of the temperature at which the crystallization of their body fluids is initiated, Tc. In fact, the correct descriptor for insects that tolerate freezing is the temperature of equilibrium freezing, Tef. The process of freezing is itself a separate physical event with unique physiological stresses that are associated with ice growth. Correspondingly there are a number of insects whose physiological cryo-limits are very specifically delineated by this transitional envelope. The distinction also has considerable significance for our understanding of insect cryobiology: firstly, because the ability to manage endogenous ice growth is a fundamental segregator of cryotype; and secondly, because our understanding of internal ice management is still largely nascent.

  4. Protein Dynamics in the Plant Extracellular Space

    Science.gov (United States)

    Guerra-Guimarães, Leonor; Pinheiro, Carla; Chaves, Inês; Barros, Danielle R.; Ricardo, Cândido P.

    2016-01-01

    The extracellular space (ECS or apoplast) is the plant cell compartment external to the plasma membrane, which includes the cell walls, the intercellular space and the apoplastic fluid (APF). The present review is focused on APF proteomics papers and intends to draw information on the metabolic processes occurring in the ECS under abiotic and biotic stresses, as well as under non-challenged conditions. The large majority of the proteins detected are involved in “cell wall organization and biogenesis”, “response to stimulus” and “protein metabolism”. It becomes apparent that some proteins are always detected, irrespective of the experimental conditions, although with different relative contribution. This fact suggests that non-challenged plants have intrinsic constitutive metabolic processes of stress/defense in the ECS. In addition to the multiple functions ascribed to the ECS proteins, should be considered the interactions established between themselves and with the plasma membrane and its components. These interactions are crucial in connecting exterior and interior of the cell, and even simple protein actions in the ECS can have profound effects on plant performance. The proteins of the ECS are permanently contributing to the high dynamic nature of this plant compartment, which seems fundamental to plant development and adaptation to the environmental conditions. PMID:28248232

  5. Micro- and macrorheology of jellyfish extracellular matrix.

    Science.gov (United States)

    Gambini, Camille; Abou, Bérengère; Ponton, Alain; Cornelissen, Annemiek J M

    2012-01-04

    Mechanical properties of the extracellular matrix (ECM) play a key role in tissue organization and morphogenesis. Rheological properties of jellyfish ECM (mesoglea) were measured in vivo at the cellular scale by passive microrheology techniques: microbeads were injected in jellyfish ECM and their Brownian motion was recorded to determine the mechanical properties of the surrounding medium. Microrheology results were compared with macrorheological measurements performed with a shear rheometer on slices of jellyfish mesoglea. We found that the ECM behaved as a viscoelastic gel at the macroscopic scale and as a much softer and heterogeneous viscoelastic structure at the microscopic scale. The fibrous architecture of the mesoglea, as observed by differential interference contrast and scanning electron microscopy, was in accord with these scale-dependent mechanical properties. Furthermore, the evolution of the mechanical properties of the ECM during aging was investigated by measuring microrheological properties at different jellyfish sizes. We measured that the ECM in adult jellyfish was locally stiffer than in juvenile ones. We argue that this stiffening is a consequence of local aggregations of fibers occurring gradually during aging of the jellyfish mesoglea and is enhanced by repetitive muscular contractions of the jellyfish.

  6. Force spectroscopy of hepatocytic extracellular matrix components

    Energy Technology Data Exchange (ETDEWEB)

    Yongsunthon, R., E-mail: YongsuntR@Corning.com [Corning Incorporated, SP-FR-01, R1S32D, Corning, NY 14831 (United States); Baker, W.A.; Bryhan, M.D.; Baker, D.E.; Chang, T.; Petzold, O.N.; Walczak, W.J.; Liu, J.; Faris, R.A.; Senaratne, W.; Seeley, L.A.; Youngman, R.E. [Corning Incorporated, SP-FR-01, R1S32D, Corning, NY 14831 (United States)

    2009-07-15

    We present atomic force microscopy and force spectroscopy data of live hepatocytes (HEPG2/C3A liver cell line) grown in Eagle's Minimum Essential Medium, a complex solution of salts and amino acids commonly used for cell culture. Contact-mode imaging and force spectroscopy of this system allowed correlation of cell morphology and extracellular matrix (ECM) properties with substrate properties. Force spectroscopy analysis of cellular 'footprints' indicated that the cells secrete large polymers (e.g., 3.5 {mu}m contour length and estimated MW 1000 kDa) onto their substrate surface. Although definitive identification of the polymers has not yet been achieved, fluorescent-labeled antibody staining has specified the presence of ECM proteins such as collagen and laminin in the cellular footprints. The stretched polymers appear to be much larger than single molecules of known ECM components, such as collagen and heparan sulfate proteoglycan, thus suggesting that the cells create larger entangled, macromolecular structures from smaller components. There is strong evidence which suggests that the composition of the ECM is greatly influenced by the hydrophobicity of the substrate surface, with preferential production and/or adsorption of larger macromolecules on hydrophobic surfaces.

  7. Characterization and biological role of extracellular vesicles

    Directory of Open Access Journals (Sweden)

    Aneta Wójtowicz

    2014-12-01

    Full Text Available Extracellular vesicles (EV form a heterogeneous population of mostly spherical membrane structures released by almost all cells, including tumour cells, both in vivo and in vitro. Their size varies from 30 nm to 1 μm, and size is one of the main criteria of the selection of two categories of EV: small (30-100 nm, more homogeneous exosomes and larger fragments (0.1-1 μm called membrane microvesicles or ectosomes. The presence of EV has already been detected in many human body fluids: blood, urine, saliva, semen and amniotic fluid. Formation of EV is tightly controlled, and their function and biochemical composition depend on the cell type they originate from. EV are the “vehicles” of bioactive molecules, such as proteins, mRNA and microRNA, and may play an important role in intercellular communication and modulation of e.g. immune system cell activity. In addition, on the surface of tumour-derived microvesicles (TMV, called oncosomes, several markers specific for cancer cells were identified, which indicates a role of TMV in tumour growth and cancer development. On the other hand, TMV may be an important source of tumour-associated antigens (TAA which can be potentially useful as biomarkers with prognostic value, as well as in development of new forms of targeted immunotherapy of cancer.

  8. Routes and mechanisms of extracellular vesicle uptake

    Directory of Open Access Journals (Sweden)

    Laura Ann Mulcahy

    2014-08-01

    Full Text Available Extracellular vesicles (EVs are small vesicles released by donor cells that can be taken up by recipient cells. Despite their discovery decades ago, it has only recently become apparent that EVs play an important role in cell-to-cell communication. EVs can carry a range of nucleic acids and proteins which can have a significant impact on the phenotype of the recipient. For this phenotypic effect to occur, EVs need to fuse with target cell membranes, either directly with the plasma membrane or with the endosomal membrane after endocytic uptake. EVs are of therapeutic interest because they are deregulated in diseases such as cancer and they could be harnessed to deliver drugs to target cells. It is therefore important to understand the molecular mechanisms by which EVs are taken up into cells. This comprehensive review summarizes current knowledge of EV uptake mechanisms. Cells appear to take up EVs by a variety of endocytic pathways, including clathrin-dependent endocytosis, and clathrin-independent pathways such as caveolin-mediated uptake, macropinocytosis, phagocytosis, and lipid raft–mediated internalization. Indeed, it seems likely that a heterogeneous population of EVs may gain entry into a cell via more than one route. The uptake mechanism used by a given EV may depend on proteins and glycoproteins found on the surface of both the vesicle and the target cell. Further research is needed to understand the precise rules that underpin EV entry into cells.

  9. Mechanics of composite cytoskeletal and extracellular networks

    Science.gov (United States)

    Das, Moumita

    2014-03-01

    Living cells sense and respond to mechanical forces in their surroundings. This mechanical response is mainly due to the cell cytoskeleton, and its interaction with the extracellular matrix (ECM). The cell cytoskeleton is a composite polymeric scaffold made of many different types of protein filaments and crosslinking proteins. Two major filament systems in the cytoskeleton are actin filaments (F-actin) and microtubules (MTs). Actin filaments are semiflexible, while the much stiffer MTs behave as rigid rods. I shall discuss theories that help understand how the direct coupling to the surrounding F-actin matrix allows intracellular MTs to bear large compressive forces and controls the range of force transmission along the MTs, and how the MTs not only enhance the stiffness of the cell cytoskeleton, but can also dramatically endow an initially nearly incompressible F-actin matrix with enhanced compressibility relative to its shear compliance. A second source of compositeness in the cytoskeleton is the presences of different types of crosslinkers that can interact cooperatively leading to enhanced mechanical rigidity and tunable response. Like the cytoskeleton, the ECM is also a polymeric composite. It is primarily composed of a mesh of fibrous proteins, mainly stiff collagen filaments, and a comparatively flexible gel of proteoglycans and hyaluronan. I shall discuss a model that shows how the interplay between the collagen network and the background elastic gel leads to a mechanically robust ECM.

  10. Extracellular matrix components in peripheral nerve regeneration.

    Science.gov (United States)

    Gonzalez-Perez, Francisco; Udina, Esther; Navarro, Xavier

    2013-01-01

    Injured axons of the peripheral nerve are able to regenerate and, eventually, reinnervate target organs. However, functional recovery is usually poor after severe nerve injuries. The switch of Schwann cells to a proliferative state, secretion of trophic factors, and the presence of extracellular matrix (ECM) molecules (such as collagen, laminin, or fibronectin) in the distal stump are key elements to create a permissive environment for axons to grow. In this review, we focus attention on the ECM components and their tropic role in axonal regeneration. These components can also be used as molecular cues to guide the axons through artificial nerve guides in attempts to better mimic the natural environment found in a degenerating nerve. Most used scaffolds tested are based on natural molecules that form the ECM, but use of synthetic polymers and functionalization of hydrogels are bringing new options. Progress in tissue engineering will eventually lead to the design of composite artificial nerve grafts that may replace the use of autologous nerve grafts to sustain regeneration over long gaps.

  11. Role of Extracellular Vesicles in Hematological Malignancies

    Directory of Open Access Journals (Sweden)

    Stefania Raimondo

    2015-01-01

    Full Text Available In recent years the role of tumor microenvironment in the progression of hematological malignancies has been widely recognized. Recent studies have focused on how cancer cells communicate within the microenvironment. Among several factors (cytokines, growth factors, and ECM molecules, a key role has been attributed to extracellular vesicles (EV, released from different cell types. EV (microvesicles and exosomes may affect stroma remodeling, host cell functions, and tumor angiogenesis by inducing gene expression modulation in target cells, thus promoting cancer progression and metastasis. Microvesicles and exosomes can be recovered from the blood and other body fluids of cancer patients and contain and deliver genetic and proteomic contents that reflect the cell of origin, thus constituting a source of new predictive biomarkers involved in cancer development and serving as possible targets for therapies. Moreover, due to their specific cell-tropism and bioavailability, EV can be considered natural vehicles suitable for drug delivery. Here we will discuss the recent advances in the field of EV as actors in hematological cancer progression, pointing out the role of these vesicles in the tumor-host interplay and in their use as biomarkers for hematological malignancies.

  12. The NIH Extracellular RNA Communication Consortium

    Directory of Open Access Journals (Sweden)

    Alexandra M. Ainsztein

    2015-08-01

    Full Text Available The Extracellular RNA (exRNA Communication Consortium, funded as an initiative of the NIH Common Fund, represents a consortium of investigators assembled to address the critical issues in the exRNA research arena. The overarching goal is to generate a multi-component community resource for sharing fundamental scientific discoveries, protocols, and innovative tools and technologies. The key initiatives include (a generating a reference catalogue of exRNAs present in body fluids of normal healthy individuals that would facilitate disease diagnosis and therapies, (b defining the fundamental principles of exRNA biogenesis, distribution, uptake, and function, as well as development of molecular tools, technologies, and imaging modalities to enable these studies, (c identifying exRNA biomarkers of disease, (d demonstrating clinical utility of exRNAs as therapeutic agents and developing scalable technologies required for these studies, and (e developing a community resource, the exRNA Atlas, to provide the scientific community access to exRNA data, standardized exRNA protocols, and other useful tools and technologies generated by funded investigators.

  13. El insomnio

    Directory of Open Access Journals (Sweden)

    F. Sarrais

    Full Text Available El insomnio es una patología muy frecuente en la población general. Se estima que de un 10 a un 15 % de la población adulta padece insomnio crónico y que un 25 a 35 % ha sufrido un insomnio ocasional o transitorio en situaciones estresantes. El objetivo de este trabajo es proporcionar información actualizada sobre el insomnio: clasificación, causas, diagnóstico diferencial, opciones terapéuticas. Para ello hemos realizado una búsqueda en Pubmed con las palabras clave "insomnio", "trastornos del sueño" y "terapia farmacológica". La evaluación del insomnio se basa en una cuidadosa historia clínica en la que se analiza el sueño, antecedentes psiquiátricos y orgánicos personales y familiares, la toma de medicamentos y otras sustancias. Los autores coinciden en afirmar que el tratamiento debe ser primeramente etiológico y secundariamente sintomático.

  14. Computational analysis of the extracellular domain of the Ca²⁺-sensing receptor: an alternate model for the Ca²⁺ sensing region.

    Science.gov (United States)

    Morrill, Gene A; Kostellow, Adele B; Gupta, Raj K

    2015-03-27

    The extracellular Ca(2+) sensing receptor (CaSR) belongs to Class C G-protein-coupled receptors (GPCRs) which include receptors for amino acids, γ-aminobutyric acid and glutamate neurotransmitters. CaSR has been described as having an extended sequence containing a Ca(2+) binding pocket within an extracellular amino (N)-terminal domain, called a Venus Fly Trap (VFT) module. CaSR is thought to consist of three domains: 1) a Ca(2+-)sensory domain, 2) a region containing 7 transmembrane (TM) helices, and 3) a carboxy (C)-terminal tail. We find that SPOCTOPUS (a combination of hidden Markov models and artificial neural networks) predicts that Homo sapiens CaSR contains two additional TM helices ((190)D - G(210); (262)S-E(282)), with the second TM helix containing a pore-lining region ((265)K - I(280)). This predicts that the putative Ca(2+) sensory domain is within an extracellular loop, N-terminal to the highly conserved heptahelical bundle. This loop contains both the cysteine-rich domain ((537)V - C(598)) and a 14 residue "linker" sequence ((599)I - F(612)) thought to support signal transmission to the heptahelical bundle. Thus domain 1 may contain a 189 residue N-terminal extracellular region followed successively by TM-1, a short intracellular loop, TM-2 and a 329 residue extracellular loop; rather than the proposed 620 residue VFT module based on crystallography of the N-terminal region of mGluR1. Since the topologies of the two proteins differ, the published CaSR VFT model is questionable. CaSR also contains multiple caveolin-binding motifs and cholesterol-binding (CRAC/CARC) domains, facilitating localization to plasma membrane lipid rafts. Ion sensing may involve combination of pore-lining regions from CaSR dimers and CaSR-bound caveolins to form ion channels capable of monitoring ionized Ca(2+) levels. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  15. El Diccionario

    OpenAIRE

    Quevedo Ganoza, Fernando; Facultad de Farmacia y Bioquímica de la Universidad Nacional Mayor de San Marcos, Lima, Perú.

    2014-01-01

    Posiblemente el libro más conocido y más frecuentemente utilizado, es el diccionario, sin embargo, es poco lo que sabemos acerca de sus orígenes, su historia y evolución.Por definición, un diccionario es un producto lexicográfico donde se reúnen por orden alfabético o ideológico todas las palabras de un idioma o una ciencia. Su empleo es universal. El término «diccionario» es muy amplio y comprende una extensa gama de variaciones; así tenemos diccionarios generales, diccionarios de términos m...

  16. El Diccionario

    OpenAIRE

    Quevedo Ganoza, Fernando; Facultad de Farmacia y Bioquímica de la Universidad Nacional Mayor de San Marcos, Lima, Perú.

    2014-01-01

    Posiblemente el libro más conocido y más frecuentemente utilizado, es el diccionario, sin embargo, es poco lo que sabemos acerca de sus orígenes, su historia y evolución.Por definición, un diccionario es un producto lexicográfico donde se reúnen por orden alfabético o ideológico todas las palabras de un idioma o una ciencia. Su empleo es universal. El término «diccionario» es muy amplio y comprende una extensa gama de variaciones; así tenemos diccionarios generales, diccionarios de términos m...

  17. El Barrio

    Directory of Open Access Journals (Sweden)

    Roberto Lira Olmo

    2015-03-01

    Full Text Available En un país que nos han acostumbrado a considerar como exitoso, tanto desde Chile como de otras latitudes, hay múltiples muestras de descontento. Hay algo indefinible en el aire que nos trae molestos. En el tiempo en que el acceso a la universidad y también al jardín infantil son los más altos de nuestra historia, en que, pese a todos las disconformidades, tenemos la mejor infraestructura que jamás tuvimos, cuando la cobertura de salud es más amplia y nuestros viejos tienen más programas de recreación, cuando todo esto y más ocurre, tenemos uno de los índices más bajos de felicidad en América. ¿Paradójico?

  18. The Extended Loop Group An Infinite Dimensional Manifold Associated with the Loop Space

    CERN Document Server

    Di Bartolo, C; Griego, J R; Bartolo, Cayetano Di; Gambini, Rodolfo; Griego, Jorge

    1993-01-01

    A set of coordinates in the non parametric loop-space is introduced. We show that these coordinates transform under infinite dimensional linear representations of the diffeomorphism group. An extension of the group of loops in terms of these objects is proposed. The enlarged group behaves locally as an infinite dimensional Lie group. Ordinary loops form a subgroup of this group. The algebraic properties of this new mathematical structure are analized in detail. Applications of the formalism to field theory, quantum gravity and knot theory are considered.

  19. Fiber reinforced composite loop space maintainer: An alternative to the conventional band and loop

    Directory of Open Access Journals (Sweden)

    Ramakrishna Yeluri

    2012-01-01

    Full Text Available The stainless steel band and loop appliance is the most commonly used fixed space maintainer in pediatric dentistry. But there are several disadvantages with this appliance such as the need for a cast or a working model, decalcification of the abutment tooth, loosening because of breakage or dissolution of the luting agent, tendency to get embedded in the soft tissue and the possibility of metal allergy. The purpose of this article is to present a simple, laboratory design of a "Fiber Reinforced Composite" (FRC loop space maintainer and discuss the advantages over the traditional band and loop space maintainers.

  20. Fiber reinforced composite loop space maintainer: An alternative to the conventional band and loop.

    Science.gov (United States)

    Yeluri, Ramakrishna; Munshi, Autar Krishen

    2012-04-01

    The stainless steel band and loop appliance is the most commonly used fixed space maintainer in pediatric dentistry. But there are several disadvantages with this appliance such as the need for a cast or a working model, decalcification of the abutment tooth, loosening because of breakage or dissolution of the luting agent, tendency to get embedded in the soft tissue and the possibility of metal allergy. The purpose of this article is to present a simple, laboratory design of a "Fiber Reinforced Composite" (FRC) loop space maintainer and discuss the advantages over the traditional band and loop space maintainers.

  1. Generalized Loop Space and Evolution of the Light-Like Wilson Loops

    CERN Document Server

    Cherednikov, I O

    2014-01-01

    Equations of motion for the light-like QCD Wilson loops are studied in the generalized loop space (GLS) setting. To this end, the classically conformal-invariant non-local variations of the cusped Wilson exponentials lying (partially) on the light-cone are formulated in terms of the Fr\\'echet derivative. The rapidity and renormalization-group behaviour of the gauge-invariant quantum correlation functions (in particular, the three-dimensional parton densities) are demonstrated to be connected to certain geometrical properties of the Wilson loops defined in the GLS.

  2. Quantum hysteresis loops in microscopic system: The loop area as a dynamical parameter

    Indian Academy of Sciences (India)

    Chandan Kumar Mondal; S P Bhattacharyya

    2001-01-01

    The area enclosed by hysteresis loops in a periodically forced bistable microscopic system at zero-temperature is examined by using the time dependent Hellmann–Feynman theorem and the Fourier grid Hamiltonian recipe for solving time-dependent Schrödinger equation. Effects of non-zero temperatures are explored with reference to a symmetric double well potential. The barrier crossing or, relaxation rates are shown to correlate systematically with the area of the loop. The possible use of hysteresis loop area in designing field parameters for optimal control is suggested.

  3. Hysteresis loop behaviors of ferroelectric thin films: A Monte Carlo simulation study

    Science.gov (United States)

    M. Bedoya-Hincapié, C.; H. Ortiz-Álvarez, H.; Restrepo-Parra, E.; J. Olaya-Flórez, J.; E. Alfonso, J.

    2015-11-01

    The ferroelectric response of bismuth titanate Bi4Ti3O12 (BIT) thin film is studied through a Monte Carlo simulation of hysteresis loops. The ferroelectric system is described by using a Diffour Hamiltonian with three terms: the electric field applied in the z direction, the nearest dipole-dipole interaction in the transversal (x-y) direction, and the nearest dipole-dipole interaction in the direction perpendicular to the thin film (the z axis). In the sample construction, we take into consideration the dipole orientations of the monoclinic and orthorhombic structures that can appear in BIT at low temperature in the ferroelectric state. The effects of temperature, stress, and the concentration of pinned dipole defects are assessed by using the hysteresis loops. The results indicate the changes in the hysteresis area with temperature and stress, and the asymmetric hysteresis loops exhibit evidence of the imprint failure mechanism with the emergence of pinned dipolar defects. The simulated shift in the hysteresis loops conforms to the experimental ferroelectric response. Project sponsored by the research departments of the Universidad Nacional de Colombia DIMA and DIB under Project 201010018227-“Crecimiento y caracterización eléctrica y estructural de películas delgadas de BixTiyOz producidas mediante Magnetrón Sputtering” and Project 12920-“Desarrollo teóricoexperimental de nanoestructuras basadas en Bismuto y materiales similares” and “Bisnano Project.”

  4. Focus on Extracellular Vesicles: Development of Extracellular Vesicle-Based Therapeutic Systems

    Directory of Open Access Journals (Sweden)

    Shin-ichiro Ohno

    2016-02-01

    Full Text Available Many types of cells release phospholipid membrane vesicles thought to play key roles in cell-cell communication, antigen presentation, and the spread of infectious agents. Extracellular vesicles (EVs carry various proteins, messenger RNAs (mRNAs, and microRNAs (miRNAs, like a “message in a bottle” to cells in remote locations. The encapsulated molecules are protected from multiple types of degradative enzymes in body fluids, making EVs ideal for delivering drugs. This review presents an overview of the potential roles of EVs as natural drugs and novel drug-delivery systems.

  5. Focus on Extracellular Vesicles: Development of Extracellular Vesicle-Based Therapeutic Systems.

    Science.gov (United States)

    Ohno, Shin-Ichiro; Drummen, Gregor P C; Kuroda, Masahiko

    2016-02-06

    Many types of cells release phospholipid membrane vesicles thought to play key roles in cell-cell communication, antigen presentation, and the spread of infectious agents. Extracellular vesicles (EVs) carry various proteins, messenger RNAs (mRNAs), and microRNAs (miRNAs), like a "message in a bottle" to cells in remote locations. The encapsulated molecules are protected from multiple types of degradative enzymes in body fluids, making EVs ideal for delivering drugs. This review presents an overview of the potential roles of EVs as natural drugs and novel drug-delivery systems.

  6. Evaluation and Comparison of Biomechanical Properties of Snail Loop with that of Opus Loop and Teardrop Loop for en masse Retraction of Anterior Teeth: FEM Study

    Directory of Open Access Journals (Sweden)

    Parikshit Rajkumar Rao

    2013-01-01

    Results: Inherently the M/F ratio produced was higher and F/D rate produced was least for opus loop compared to snail loop and teardrop loop. Conclusion: With incorporation of 20°gable bends snail loop prepared in 0.017 × 0.025 inch and 0.019 × 0.025 inch TMA wire is very efficient to deliver M/F ratio required for translatory tooth movement with acceptable F/D rate. Snail loop is easy to fabricate and finer shape morphology prevents tissue impingement.

  7. Designing Self-Organized Contextualized Feedback Loops

    NARCIS (Netherlands)

    Kalz, Marco

    2013-01-01

    Kalz, M. (2013). Designing Self-Organized Contextualized Feedback Loops. In D. Whitelock, W. Warburton, G. Wills, & L. Gilbert (Eds.), International Conference on Computer Assisted Assessment (CAA 2013). July, 9-10, 2013, University of Southampton, Southampton, UK. http://caaconference.com.

  8. Calculating Electromagnetic Fields Of A Loop Antenna

    Science.gov (United States)

    Schieffer, Mitchell B.

    1987-01-01

    Approximate field values computed rapidly. MODEL computer program developed to calculate electromagnetic field values of large loop antenna at all distances to observation point. Antenna assumed to be in x-y plane with center at origin of coordinate system. Calculates field values in both rectangular and spherical components. Also solves for wave impedance. Written in MicroSoft FORTRAN 77.

  9. The Alpine loop of the tethys zone

    NARCIS (Netherlands)

    Bemmelen, R.W. van

    1969-01-01

    The Alpine loop in Europe results from semi-autochthonous crustal movements which are restricted to the mobile Tethys zone. Its evolution cannot be explained by a uniform northward drift and push of the African continent; it has to be sought, in the first place, in geodynamic processes occurring in

  10. Black hole entropy in loop quantum gravity

    Science.gov (United States)

    Agulló, Iván; Barbero G, J. Fernando; Borja, E. F.; Díaz-Polo, Jacobo; Villaseñor, Eduardo J. S.

    2012-05-01

    We discuss the recent progress on black hole entropy in loop quantum gravity, focusing in particular on the recently discovered discretization effect for microscopic black holes. Powerful analytical techniques have been developed to perform the exact computation of entropy. A statistical analysis of the structures responsible for this effect shows its progressive damping and eventual disappearance as one increases the considered horizon area.

  11. Closed-loop control of magnetotactic bacteria

    NARCIS (Netherlands)

    Khalil, I.S.M.; Pichel, M.P.; Abelmann, L.; Misra, S.

    2013-01-01

    Realization of point-to-point positioning of a magnetotactic bacterium (MTB) necessitates the application of a relatively large magnetic field gradients to decrease its velocity in the vicinity of a reference position. We investigate an alternative closed-loop control approach to position the MTB. T

  12. Loop quantum gravity; Gravedad cuantica de lazos

    Energy Technology Data Exchange (ETDEWEB)

    Pullin, J.

    2015-07-01

    Loop quantum gravity is one of the approaches that are being studied to apply the rules of quantum mechanics to the gravitational field described by the theory of General Relativity . We present an introductory summary of the main ideas and recent results. (Author)

  13. Polyakov Loop Correlations at Large N

    CERN Document Server

    Neuberger, Herbert

    2014-01-01

    I describe a study of the two-point single-eigenvalue distribution correlation function of Polyakov loops in the confined phase of four dimensional SU(N) YM theory at large N. The reasons for the interest in this correlation function are explained. Analytical and numerical results are presented. Brief conclusions are drawn.

  14. Fun with higher-loop Feynman diagrams

    Science.gov (United States)

    Luthe, Thomas; Schröder, York

    2016-10-01

    We review recent progress that we have achieved in evaluating the class of fully massive vacuum integrals at five loops. After discussing topics that arise in classification, evaluation and algorithmic codification of this specific set of Feynman integrals, we present some selected new results for their expansions around 4 — 2ε dimensions.

  15. Loop Quantum Cosmology and the CMB

    Science.gov (United States)

    Agullo, Ivan

    2017-01-01

    This talk will provide an up-to-date summary of phenomenological explorations in loop quantum cosmology. The possibility of a quantum gravity origin of the anomalies observed in the cosmic microwave background at large angular scales will be discussed. The talk will also provide some background material for subsequent contributions in the same session. NSF PHYS-1403943.

  16. Think Math! Interactive Loops for Groups.

    Science.gov (United States)

    Bulla, Dale

    This book contains activities using a technique that allows students to practice routine arithmetical operations without getting bored. Math Loops is a game in which each student receives a card containing answers to a mathematics question or problem and must listen for another student to call out the question. As the game progresses around the…

  17. Geometry of the analytic loop group

    NARCIS (Netherlands)

    De Concini, C.; Hernandez, D.; Reshetikhin, N.

    2013-01-01

    We introduce and study a notion of analytic loop group with a Riemann-Hilbert factorization relevant for the representation theory of quantum affine algebras at roots of unity View the MathML source with non-trivial central charge. We introduce a Poisson structure and study properties of its Poisson

  18. Quenched chiral perturbation theory to one loop

    NARCIS (Netherlands)

    Colangelo, Gilberto; Pallante, Elisabetta

    1998-01-01

    We calculate the divergences of the generating functional of quenched chiral perturbation theory at one loop, and renormalize the theory by an appropriate definition of the counterterms. We show that the quenched chiral logarithms can be accounted for by defining a renormalized B0 parameter which, a

  19. Quenched Chiral Perturbation Theory to one loop

    NARCIS (Netherlands)

    Colangelo, G.; Pallante, E.

    1998-01-01

    The divergences of the generating functional of quenched Chiral Perturbation theory (qCHPT) to one loop are computed in closed form. We show how the quenched chiral logarithms can be reabsorbed in the renormalization of the B0 parameter of the leading order Lagrangian. Finally, we do the chiral powe

  20. Volume reduction through perturbative Wilson loops

    CERN Document Server

    Perez, Margarita Garcia; Okawa, Masanori

    2016-01-01

    We derive the perturbative expansion of Wilson loops to order g^4 in a SU(N) lattice gauge theory with twisted boundary conditions. Our expressions show that the thermodynamic limit is attained at infinite N for any number of lattice sites and allow to quantify the deviations from volume independence at finite large N as a function of the twist.