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Sample records for conformational determinants signal

  1. Alternative SAIL-Trp for robust aromatic signal assignment and determination of the {chi}{sub 2} conformation by intra-residue NOEs

    Energy Technology Data Exchange (ETDEWEB)

    Miyanoiri, Yohei; Takeda, Mitsuhiro [Nagoya University, Graduate School of Science, Structural Biology Research Center (Japan); Jee, JunGoo; Ono, Akira M.; Okuma, Kosuke; Terauchi, Tsutomu [Tokyo Metropolitan University, Center for Priority Areas (Japan); Kainosho, Masatsune, E-mail: kainosho@nagoya-u.jp [Nagoya University, Graduate School of Science, Structural Biology Research Center (Japan)

    2011-12-15

    Tryptophan (Trp) residues are frequently found in the hydrophobic cores of proteins, and therefore, their side-chain conformations, especially the precise locations of the bulky indole rings, are critical for determining structures by NMR. However, when analyzing [U-{sup 13}C,{sup 15}N]-proteins, the observation and assignment of the ring signals are often hampered by excessive overlaps and tight spin couplings. These difficulties have been greatly alleviated by using stereo-array isotope labeled (SAIL) proteins, which are composed of isotope-labeled amino acids optimized for unambiguous side-chain NMR assignment, exclusively through the {sup 13}C-{sup 13}C and {sup 13}C-{sup 1}H spin coupling networks (Kainosho et al. in Nature 440:52-57, 2006). In this paper, we propose an alternative type of SAIL-Trp with the [{zeta}2,{zeta}3-{sup 2}H{sub 2}; {delta}1,{epsilon}3,{eta}2-{sup 13}C{sub 3}; {epsilon}1-{sup 15}N]-indole ring ([{sup 12}C{sub {gamma},}{sup 12}C{sub {epsilon}2}] SAIL-Trp), which provides a more robust way to correlate the {sup 1}H{sub {beta}}, {sup 1}H{sub {alpha}}, and {sup 1}H{sub N} to the {sup 1}H{sub {delta}1} and {sup 1}H{sub {epsilon}3} through the intra-residue NOEs. The assignment of the {sup 1}H{sub {delta}1}/{sup 13}C{sub {delta}1} and {sup 1}H{sub {epsilon}3}/{sup 13}C{sub {epsilon}3} signals can thus be transferred to the {sup 1}H{sub {epsilon}1}/{sup 15}N{sub {epsilon}1} and {sup 1}H{sub {eta}2}/{sup 13}C{sub {eta}2} signals, as with the previous type of SAIL-Trp, which has an extra {sup 13}C at the C{sub {gamma}} of the ring. By taking advantage of the stereospecific deuteration of one of the prochiral {beta}-methylene protons, which was {sup 1}H{sub {beta}2} in this experiment, one can determine the side-chain conformation of the Trp residue including the {chi}{sub 2} angle, which is especially important for Trp residues, as they can adopt three preferred conformations. We demonstrated the usefulness of [{sup 12}C{sub {gamma}},{sup 12}C

  2. Alternative SAIL-Trp for robust aromatic signal assignment and determination of the χ2 conformation by intra-residue NOEs

    International Nuclear Information System (INIS)

    Miyanoiri, Yohei; Takeda, Mitsuhiro; Jee, JunGoo; Ono, Akira M.; Okuma, Kosuke; Terauchi, Tsutomu; Kainosho, Masatsune

    2011-01-01

    Tryptophan (Trp) residues are frequently found in the hydrophobic cores of proteins, and therefore, their side-chain conformations, especially the precise locations of the bulky indole rings, are critical for determining structures by NMR. However, when analyzing [U– 13 C, 15 N]-proteins, the observation and assignment of the ring signals are often hampered by excessive overlaps and tight spin couplings. These difficulties have been greatly alleviated by using stereo-array isotope labeled (SAIL) proteins, which are composed of isotope-labeled amino acids optimized for unambiguous side-chain NMR assignment, exclusively through the 13 C– 13 C and 13 C– 1 H spin coupling networks (Kainosho et al. in Nature 440:52–57, 2006). In this paper, we propose an alternative type of SAIL-Trp with the [ζ2,ζ3- 2 H 2 ; δ1,ε3,η2- 13 C 3 ; ε1- 15 N]-indole ring ([ 12 C γ, 12 C ε2 ] SAIL-Trp), which provides a more robust way to correlate the 1 H β , 1 H α , and 1 H N to the 1 H δ1 and 1 H ε3 through the intra-residue NOEs. The assignment of the 1 H δ1 / 13 C δ1 and 1 H ε3 / 13 C ε3 signals can thus be transferred to the 1 H ε1 / 15 N ε1 and 1 H η2 / 13 C η2 signals, as with the previous type of SAIL-Trp, which has an extra 13 C at the C γ of the ring. By taking advantage of the stereospecific deuteration of one of the prochiral β-methylene protons, which was 1 H β2 in this experiment, one can determine the side-chain conformation of the Trp residue including the χ 2 angle, which is especially important for Trp residues, as they can adopt three preferred conformations. We demonstrated the usefulness of [ 12 C γ , 12 C ε2 ] SAIL-Trp for the 12 kDa DNA binding domain of mouse c-Myb protein (Myb-R2R3), which contains six Trp residues.

  3. Alternative SAIL-Trp for robust aromatic signal assignment and determination of the χ(2) conformation by intra-residue NOEs.

    Science.gov (United States)

    Miyanoiri, Yohei; Takeda, Mitsuhiro; Jee, JunGoo; Ono, Akira M; Okuma, Kosuke; Terauchi, Tsutomu; Kainosho, Masatsune

    2011-12-01

    Tryptophan (Trp) residues are frequently found in the hydrophobic cores of proteins, and therefore, their side-chain conformations, especially the precise locations of the bulky indole rings, are critical for determining structures by NMR. However, when analyzing [U-(13)C,(15)N]-proteins, the observation and assignment of the ring signals are often hampered by excessive overlaps and tight spin couplings. These difficulties have been greatly alleviated by using stereo-array isotope labeled (SAIL) proteins, which are composed of isotope-labeled amino acids optimized for unambiguous side-chain NMR assignment, exclusively through the (13)C-(13)C and (13)C-(1)H spin coupling networks (Kainosho et al. in Nature 440:52-57, 2006). In this paper, we propose an alternative type of SAIL-Trp with the [ζ2,ζ3-(2)H(2); δ1,ε3,η2-(13)C(3); ε1-(15)N]-indole ring ([(12)C (γ,) ( 12) C(ε2)] SAIL-Trp), which provides a more robust way to correlate the (1)H(β), (1)H(α), and (1)H(N) to the (1)H(δ1) and (1)H(ε3) through the intra-residue NOEs. The assignment of the (1)H(δ1)/(13)C(δ1) and (1)H(ε3)/(13)C(ε3) signals can thus be transferred to the (1)H(ε1)/(15)N(ε1) and (1)H(η2)/(13)C(η2) signals, as with the previous type of SAIL-Trp, which has an extra (13)C at the C(γ) of the ring. By taking advantage of the stereospecific deuteration of one of the prochiral β-methylene protons, which was (1)H(β2) in this experiment, one can determine the side-chain conformation of the Trp residue including the χ(2) angle, which is especially important for Trp residues, as they can adopt three preferred conformations. We demonstrated the usefulness of [(12)C(γ),(12)C(ε2)] SAIL-Trp for the 12 kDa DNA binding domain of mouse c-Myb protein (Myb-R2R3), which contains six Trp residues.

  4. Conformational biosensors reveal GPCR signalling from endosomes

    DEFF Research Database (Denmark)

    Irannejad, R; Tomshine, Jin C; Tomshine, Jon R

    2013-01-01

    A long-held tenet of molecular pharmacology is that canonical signal transduction mediated by G-protein-coupled receptor (GPCR) coupling to heterotrimeric G proteins is confined to the plasma membrane. Evidence supporting this traditional view is based on analytical methods that provide limited...... or no subcellular resolution. It has been subsequently proposed that signalling by internalized GPCRs is restricted to G-protein-independent mechanisms such as scaffolding by arrestins, or GPCR activation elicits a discrete form of persistent G protein signalling, or that internalized GPCRs can indeed contribute...... in the early endosome membrane, and that internalized receptors contribute to the overall cellular cyclic AMP response within several minutes after agonist application. These findings provide direct support for the hypothesis that canonical GPCR signalling occurs from endosomes as well as the plasma membrane...

  5. Allosteric conformational barcodes direct signaling in the cell.

    Science.gov (United States)

    Nussinov, Ruth; Ma, Buyong; Tsai, Chung-Jung; Csermely, Peter

    2013-09-03

    The cellular network is highly interconnected. Pathways merge and diverge. They proceed through shared proteins and may change directions. How are cellular pathways controlled and their directions decided, coded, and read? These questions become particularly acute when we consider that a small number of pathways, such as signaling pathways that regulate cell fates, cell proliferation, and cell death in development, are extensively exploited. This review focuses on these signaling questions from the structural standpoint and discusses the literature in this light. All co-occurring allosteric events (including posttranslational modifications, pathogen binding, and gain-of-function mutations) collectively tag the protein functional site with a unique barcode. The barcode shape is read by an interacting molecule, which transmits the signal. A conformational barcode provides an intracellular address label, which selectively favors binding to one partner and quenches binding to others, and, in this way, determines the pathway direction, and, eventually, the cell's response and fate. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Determinants of conformal wave operators in four dimensions

    International Nuclear Information System (INIS)

    Blau, S.K.; Visser, M.; Wipf, A.

    1988-01-01

    We consider conformally coupled wave operators in four dimensions. Such operators are associated with conformally coupled massless scalars, massless spin 1/2 particles, and abelian gauge bosons. We explicitly calculate the change in the determinant of these wave operators as a function of conformal deformations of the background metric. This variation is given in terms of a geometrical object, the second Seeley-de Witt coefficient. (orig.)

  7. CD2 probe infrared method for determining polymethylene chain conformation

    International Nuclear Information System (INIS)

    Maroncelli, M.; Strauss, H.L.; Snyder, R.G.

    1985-01-01

    The rocking mode frequency of a CD 2 group substituted in a polymethylene chain is sensitive to conformation in the immediate vicinity of the CD 2 group. This sensitivity forms the basis of a commonly used infrared method for determining site-specific conformation in polymethylene systems. In the present work, the CD 2 probe method has been extended and quantified with the use of infrared data on model CD 2 -substituted n-alkanes. The frequency of the CD 2 rocking band is determined primarily by the conformation of adjoining CC bonds, i.e., by tt, gt, and gg pairs. However, we have found that there are significant frequency shifts associated with other factors. These include the conformation of the next nearest CC bonds, both with the CD 2 positioned at the end and in the interior of the chain, and chain length. In addition, the ratio of the absorptivities of the tt to gt bands has been established. These results enable the method to provide new details about the conformation of the chains in polymethylene systems and reliable estimates of the concentrations of specific kinds of short conformational sequences. 14 references, 6 figures, 2 tables

  8. Conformations and orientations of a signal peptide interacting with phospholipid monolayers

    International Nuclear Information System (INIS)

    Cornell, D.G.; Dluhy, R.A.; Briggs, M.S.; McKnight, C.J.; Gierasch, L.M.

    1989-01-01

    The interaction of a chemically synthesized 25-residue signal peptide of LamB protein from Escherichia coli with phospholipids has been studied with a film balance technique. The conformation, orientation, and concentration of the peptides in lipid monolayers have been determined from polarized infrared spectroscopy, ultraviolet spectroscopy, and assay of 14 C-labeled peptide in transferred films. When the LamB signal peptide in injected into the subphase under a phosphatidylethanolamine-phosphatidylglycerol monolayer at low initial pressure, insertion of a portion of the peptide into the lipid film is evidenced by a rapid rise in film pressure. Spectroscopic results obtained on films transferred to quartz plates and Ge crystals show that the peptide is a mixture of α-helix and β-conformation where the long axis of the α-helix penetrates the monolayer plane and the β-structure which is coplanar with the film. By contrast, when peptide is injected under lipid at high initial pressure, no pressure rise is observed, and the spectroscopic results show the presence of only β-structure which is coplanar with the monolayer. The spectroscopic and radioassay results are all consistent with the picture of a peptide anchored to the monolayer through electrostatic binding with a helical portion inserted into the lipid region of the monolayer and a β-structure portion resident in the aqueous phase. The negative charges on the lipid molecules are roughly neutralized by the positive charges of the peptide

  9. Determinants and conformal anomalies of GJMS operators on spheres

    Science.gov (United States)

    Dowker, J. S.

    2011-03-01

    The conformal anomalies and functional determinants of the Branson-GJMS operators, P2k, on the d-dimensional sphere are evaluated in explicit terms for any d and k such that k rational multiplicative anomaly, which vanishes for odd d. Taking the mode system on the sphere as the union of Neumann and Dirichlet ones on the hemisphere is a basic part of the method and leads to a heuristic explanation of the non-existence of 'super-critical' operators, 2k > d for even d. Significant use is made of the Barnes zeta function. The results are given in terms of ratios of determinants of operators on a (d + 1)-dimensional bulk dual sphere. For odd dimensions, the log determinant is written in terms of multiple sine functions and agreement is found with holographic computations, yielding an integral over a Plancherel measure. The N-D determinant ratio is also found explicitly for even dimensions. Ehrhart polynomials are encountered.

  10. Outside-In Signal Transmission by Conformational Changes in Integrin Mac-11

    Science.gov (United States)

    Lefort, Craig T.; Hyun, Young-Min; Schultz, Joanne B.; Law, Foon-Yee; Waugh, Richard E.; Knauf, Philip A.; Kim, Minsoo

    2010-01-01

    Intracellular signals associated with or triggered by integrin ligation can control cell survival, differentiation, proliferation, and migration. Despite accumulating evidence that conformational changes regulate integrin affinity to its ligands, how integrin structure regulates signal transmission from the outside to the inside of the cell remains elusive. Using fluorescence resonance energy transfer, we addressed whether conformational changes in integrin Mac-1 are sufficient to transmit outside-in signals in human neutrophils. Mac-1 conformational activation induced by ligand occupancy or activating Ab binding, but not integrin clustering, triggered similar patterns of intracellular protein tyrosine phosphorylation, including Akt phosphorylation, and inhibited spontaneous neutrophil apoptosis, indicating that global conformational changes are critical for Mac-1-dependent outside-in signal transduction. In neutrophils and myeloid K562 cells, ligand ICAM-1 or activating Ab binding promoted switchblade-like extension of the Mac-1 extracellular domain and separation of the αM and β2 subunit cytoplasmic tails, two structural hallmarks of integrin activation. These data suggest the primacy of global conformational changes in the generation of Mac-1 outside-in signals. PMID:19864611

  11. Conformational analysis of g protein-coupled receptor signaling by hydrogen/deuterium exchange mass spectrometry.

    Science.gov (United States)

    Li, Sheng; Lee, Su Youn; Chung, Ka Young

    2015-01-01

    Conformational change and protein-protein interactions are two major mechanisms of membrane protein signal transduction, including G protein-coupled receptors (GPCRs). Upon agonist binding, GPCRs change conformation, resulting in interaction with downstream signaling molecules such as G proteins. To understand the precise signaling mechanism, studies have investigated the structural mechanism of GPCR signaling using X-ray crystallography, nuclear magnetic resonance (NMR), or electron paramagnetic resonance. In addition to these techniques, hydrogen/deuterium exchange mass spectrometry (HDX-MS) has recently been used in GPCR studies. HDX-MS measures the rate at which peptide amide hydrogens exchange with deuterium in the solvent. Exposed or flexible regions have higher exchange rates and excluded or ordered regions have lower exchange rates. Therefore, HDX-MS is a useful tool for studying protein-protein interfaces and conformational changes after protein activation or protein-protein interactions. Although HDX-MS does not give high-resolution structures, it analyzes protein conformations that are difficult to study with X-ray crystallography or NMR. Furthermore, conformational information from HDX-MS can help in the crystallization of X-ray crystallography by suggesting highly flexible regions. Interactions between GPCRs and downstream signaling molecules are not easily analyzed by X-ray crystallography or NMR because of the large size of the GPCR-signaling molecule complexes, hydrophobicity, and flexibility of GPCRs. HDX-MS could be useful for analyzing the conformational mechanism of GPCR signaling. In this chapter, we discuss details of HDX-MS for analyzing GPCRs using the β2AR-G protein complex as a model system. © 2015 Elsevier Inc. All rights reserved.

  12. Determinants and conformal anomalies of GJMS operators on spheres

    Energy Technology Data Exchange (ETDEWEB)

    Dowker, J S, E-mail: dowker@man.ac.uk [Theory Group, School of Physics and Astronomy, University of Manchester, Manchester (United Kingdom)

    2011-03-18

    The conformal anomalies and functional determinants of the Branson-GJMS operators, P{sub 2k}, on the d-dimensional sphere are evaluated in explicit terms for any d and k such that k {<=} d/2 (if d is even). The determinants are given in terms of multiple gamma functions and a rational multiplicative anomaly, which vanishes for odd d. Taking the mode system on the sphere as the union of Neumann and Dirichlet ones on the hemisphere is a basic part of the method and leads to a heuristic explanation of the non-existence of 'super-critical' operators, 2k > d for even d. Significant use is made of the Barnes zeta function. The results are given in terms of ratios of determinants of operators on a (d + 1)-dimensional bulk dual sphere. For odd dimensions, the log determinant is written in terms of multiple sine functions and agreement is found with holographic computations, yielding an integral over a Plancherel measure. The N-D determinant ratio is also found explicitly for even dimensions. Ehrhart polynomials are encountered.

  13. Determinants and conformal anomalies of GJMS operators on spheres

    International Nuclear Information System (INIS)

    Dowker, J S

    2011-01-01

    The conformal anomalies and functional determinants of the Branson-GJMS operators, P 2k , on the d-dimensional sphere are evaluated in explicit terms for any d and k such that k ≤ d/2 (if d is even). The determinants are given in terms of multiple gamma functions and a rational multiplicative anomaly, which vanishes for odd d. Taking the mode system on the sphere as the union of Neumann and Dirichlet ones on the hemisphere is a basic part of the method and leads to a heuristic explanation of the non-existence of 'super-critical' operators, 2k > d for even d. Significant use is made of the Barnes zeta function. The results are given in terms of ratios of determinants of operators on a (d + 1)-dimensional bulk dual sphere. For odd dimensions, the log determinant is written in terms of multiple sine functions and agreement is found with holographic computations, yielding an integral over a Plancherel measure. The N-D determinant ratio is also found explicitly for even dimensions. Ehrhart polynomials are encountered.

  14. 40 CFR 93.157 - Frequency of conformity determinations.

    Science.gov (United States)

    2010-07-01

    ... convenience of the user, the revised text is set forth as follows: § 93.157 Reevaluation of conformity. (a... were below the limits in § 93.153(b) and changes to the action would result in the total emissions from the action being above the limits in § 93.153(b), then the Federal agency must make a conformity...

  15. Conformation of antifreeze glycoproteins as determined from conformational energy calculations and fully assigned proton NMR spectra

    International Nuclear Information System (INIS)

    Bush, C.A.; Rao, B.N.N.

    1986-01-01

    The 1 H NMR spectra of AFGP's ranging in molecular weight from 2600 to 30,000 Daltons isolated from several different species of polar fish have been measured. The spectrum of AFGP 1-4 from Pagothenia borchgrevinki with an average of 30 repeating subunits has a single resonance for each proton of the glycotripeptide repeating unit, (ala-[gal-(β-1→3) galNAc-(α--O-]thr-ala)/sub n/. Its 1 H NMR spectrum including resonances of the amide protons has been completely assigned. Coupling constants and nuclear Overhauser enhancements (n.O.e.) between protons on distant residues imply conformational order. The 2600 dalton molecular weight glycopeptides (AFGP-8) have pro in place of ala at certain specific points in the sequence and AFGP-8R of Eleginus gracilis has arg in place of one thr. The resonances of pro and arg were assigned by decoupling. The resonances of the carboxy and amino terminals have distinct chemical shifts and were assigned in AFGP-8 of Boreogadus saida by titration. n.O.e. between α--protons and amide protons of the adjacent residue (sequential n.O.e.) were used in assignments of additional resonances and to assign the distinctive resonances of thr followed by pro. Conformational energy calculations on the repeating glycotripeptide subunit of AFGP show that the α--glucosidic linkage has a fixed conformation while the β--linkage is less rigid. A conformational model for AFGP 1-4, which is based on the calculations has the peptide in an extended left-handed helix with three residues per turn similar to polyproline II. The model is consistent with CD data, amide proton coupling constants, temperature dependence of amide proton chemical shifts

  16. Conformational determinants of the intracellular localization of midkine

    International Nuclear Information System (INIS)

    Dai Lichen; Xu, Diyong; Yao Xing; Lu Yongliang; Xu Zhengping

    2005-01-01

    Midkine (MK) is a multifunctional growth factor and has been discovered to play important roles in carcinogenesis. MK has been reported to localize to the nucleus and nucleolus, however, the data are not consistent and the signals responsible for the localization are unknown. Here we reported that human MK exclusively localized to the nucleus and nucleolus in HepG2 cells by using GFP as a tracking molecule. In order to identify the motifs required for the nuclear localization and nucleolar accumulation, point- and deletion-mutations were introduced and the corresponding subcellular localizations were analyzed. Data revealed that (i) K79R81, K86K87, and the C-terminal tail of MK constitute the nuclear localization determinant of MK, and (ii) the C-terminal tail is the key element controlling MK nucleolar accumulation though the N-terminal tail, K79R81, and K86K87 also contribute to this process. Taken together, our results provide the first documentation about the determinants required for MK nuclear and nucleolar localization

  17. Conformational determination of [Leu]enkephalin based on theoretical and experimental VA and VCD spectral analyses

    DEFF Research Database (Denmark)

    Abdali, Salim; Jalkanen, Karl J.; Cao, X.

    2004-01-01

    Conformational determination of [Leu]enkephalin in DMSO-d6 is carried out using VA and VCD spectral analyses. Conformational energies, vibrational frequencies and VA and VCD intensities are calculated using DFT at B3LYP/6-31G* level of theory. Comparison between the measured spectra...

  18. Direct Position Determination of Multiple Radio Signals

    Directory of Open Access Journals (Sweden)

    Weiss Anthony J

    2005-01-01

    Full Text Available The most common methods for position determination of radio signal emitters such as communications or radar transmitters are based on measuring a specified parameter such as angle of arrival (AOA or time of arrival (TOA of the signal. The measured parameters are then used to estimate the transmitter's location. Since the measurements are done at each base station independently, without using the constraint that the AOA/TOA estimates at different base stations should correspond to the same transmitter's location, this is a suboptimal location determination technique. Further, if the number of array elements at each base station is , and the signal waveforms are unknown, the number of cochannel simultaneous transmitters that can be localized by AOA is limited to . Also, most AOA algorithms fail when the sources are not well angularly separated. We propose a technique that uses exactly the same data as the common AOA methods but the position determination is direct. The proposed method can handle more than cochannel simultaneous signals. Although there are many stray parameters, only a two-dimensional search is required for a planar geometry. The technique provides a natural solution to the measurements sources association problem that is encountered in AOA-based location systems. In addition to new algorithms, we provide analytical performance analysis, Cramér-Rao bounds and Monte Carlo simulations. We demonstrate that the proposed approach frequently outperforms the traditional AOA methods for unknown as well as known signal waveforms.

  19. Microscopic insight into thermodynamics of conformational changes of SAP-SLAM complex in signal transduction cascade

    Science.gov (United States)

    Samanta, Sudipta; Mukherjee, Sanchita

    2017-04-01

    The signalling lymphocytic activation molecule (SLAM) family of receptors, expressed by an array of immune cells, associate with SLAM-associated protein (SAP)-related molecules, composed of single SH2 domain architecture. SAP activates Src-family kinase Fyn after SLAM ligation, resulting in a SLAM-SAP-Fyn complex, where, SAP binds the Fyn SH3 domain that does not involve canonical SH3 or SH2 interactions. This demands insight into this SAP mediated signalling cascade. Thermodynamics of the conformational changes are extracted from the histograms of dihedral angles obtained from the all-atom molecular dynamics simulations of this structurally well characterized SAP-SLAM complex. The results incorporate the binding induced thermodynamic changes of individual amino acid as well as the secondary structural elements of the protein and the solvent. Stabilization of the peptide partially comes through a strong hydrogen bonding network with the protein, while hydrophobic interactions also play a significant role where the peptide inserts itself into a hydrophobic cavity of the protein. SLAM binding widens SAP's second binding site for Fyn, which is the next step in the signal transduction cascade. The higher stabilization and less fluctuation of specific residues of SAP in the Fyn binding site, induced by SAP-SLAM complexation, emerge as the key structural elements to trigger the recognition of SAP by the SH3 domain of Fyn. The thermodynamic quantification of the protein due to complexation not only throws deeper understanding in the established mode of SAP-SLAM interaction but also assists in the recognition of the relevant residues of the protein responsible for alterations in its activity.

  20. Fragment-based identification of determinants of conformational and spectroscopic change at the ricin active site

    Directory of Open Access Journals (Sweden)

    Soares Alexei S

    2007-11-01

    Full Text Available Abstract Background Ricin is a potent toxin and known bioterrorism threat with no available antidote. The ricin A-chain (RTA acts enzymatically to cleave a specific adenine base from ribosomal RNA, thereby blocking translation. To understand better the relationship between ligand binding and RTA active site conformational change, we used a fragment-based approach to find a minimal set of bonding interactions able to induce rearrangements in critical side-chain positions. Results We found that the smallest ligand stabilizing an open conformer of the RTA active site pocket was an amide group, bound weakly by only a few hydrogen bonds to the protein. Complexes with small amide-containing molecules also revealed a switch in geometry from a parallel towards a splayed arrangement of an arginine-tryptophan cation-pi interaction that was associated with an increase and red-shift in tryptophan fluorescence upon ligand binding. Using the observed fluorescence signal, we determined the thermodynamic changes of adenine binding to the RTA active site, as well as the site-specific binding of urea. Urea binding had a favorable enthalpy change and unfavorable entropy change, with a ΔH of -13 ± 2 kJ/mol and a ΔS of -0.04 ± 0.01 kJ/(K*mol. The side-chain position of residue Tyr80 in a complex with adenine was found not to involve as large an overlap of rings with the purine as previously considered, suggesting a smaller role for aromatic stacking at the RTA active site. Conclusion We found that amide ligands can bind weakly but specifically to the ricin active site, producing significant shifts in positions of the critical active site residues Arg180 and Tyr80. These results indicate that fragment-based drug discovery methods are capable of identifying minimal bonding determinants of active-site side-chain rearrangements and the mechanistic origins of spectroscopic shifts. Our results suggest that tryptophan fluorescence provides a sensitive probe for the

  1. Attractor Structures of Signaling Networks: Consequences of Different Conformational Barcode Dynamics and Their Relations to Network-Based Drug Design.

    Science.gov (United States)

    Szalay, Kristóf Z; Nussinov, Ruth; Csermely, Peter

    2014-06-01

    Conformational barcodes tag functional sites of proteins and are decoded by interacting molecules transmitting the incoming signal. Conformational barcodes are modified by all co-occurring allosteric events induced by post-translational modifications, pathogen, drug binding, etc. We argue that fuzziness (plasticity) of conformational barcodes may be increased by disordered protein structures, by integrative plasticity of multi-phosphorylation events, by increased intracellular water content (decreased molecular crowding) and by increased action of molecular chaperones. This leads to increased plasticity of signaling and cellular networks. Increased plasticity is both substantiated by and inducing an increased noise level. Using the versatile network dynamics tool, Turbine (www.turbine.linkgroup.hu), here we show that the 10 % noise level expected in cellular systems shifts a cancer-related signaling network of human cells from its proliferative attractors to its largest, apoptotic attractor representing their health-preserving response in the carcinogen containing and tumor suppressor deficient environment modeled in our study. Thus, fuzzy conformational barcodes may not only make the cellular system more plastic, and therefore more adaptable, but may also stabilize the complex system allowing better access to its largest attractor. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Conformational determinants of phosphotyrosine peptides complexed with the Src SH2 domain.

    Directory of Open Access Journals (Sweden)

    Joseph Nachman

    2010-06-01

    Full Text Available The inhibition of specific SH2 domain mediated protein-protein interactions as an effective chemotherapeutic approach in the treatment of diseases remains a challenge. That different conformations of peptide-ligands are preferred by different SH2 domains is an underappreciated observation from the structural analysis of phosphotyrosine peptide binding to SH2 domains that may aid in future drug design. To explore the nature of ligand binding, we use simulated annealing (SA to sample the conformational space of phosphotyrosine-containing peptides complexed with the Src SH2 domain. While in good agreement with the crystallographic and NMR studies of high-affinity phosphopeptide-SH2 domain complexes, the results suggest that the structural basis for phopsphopeptide- Src SH2 interactions is more complex than the "two-pronged plug two-hole socket" model. A systematic study of peptides of type pYEEX, where pY is phosphotyrosine and X is a hydrophobic residue, indicates that these peptides can assume two conformations, one extended and one helical, representing the balance between the interaction of residue X with the hydrophobic hole on the surface of the Src SH2 domain, and its contribution to the inherent tendency of the two glutamic acids to form an alpha-helix. In contrast, a beta-turn conformation, almost identical to that observed in the crystal structure of pYVNV bound to the Grb2 SH2 domain, predominates for pYXNX peptides, even in the presence of isoleucine at the third position. While peptide binding affinities, as measured by fluorescence polarization, correlate with the relative proportion of extended peptide conformation, these results suggest a model where all three residues C-terminal to the phosphotyrosine determine the conformation of the bound phosphopeptide. The information obtained in this work can be used in the design of specific SH2 domain inhibitors.

  3. Application of solid-state tritium NMR in determining the bioactive conformation of paclitaxel

    International Nuclear Information System (INIS)

    Lin, T.

    2012-01-01

    The determination of the conformation of small molecule bound to its biological target would facilitate people to design improved drugs. This determination can be difficult due to technical limitations, as exemplified by the long standing debate on the microtubule-binding conformation of a natural anticancer drug - paclitaxel. Previous studies using X-ray crystallography and solution-state NMR failed to furnish direct information on the expected conformation. Solid-state NMR may help in this task by providing precise interatomic distances, and the selective labeling on different sites with tritium atoms enables accurate measurement of long-range distances (up to 14.4 Angstroms) owing to the high gyromagnetic ratio of this nucleus, without any structural modification of the molecule. So our project aiming at illustrating the bioactive conformation of paclitaxel consists the syntheses of 6 different paclitaxel isotopomers bearing a pair of tritium at specified positions, flowing by the preparations of corresponding microtubule-labeled paclitaxel complexes. The solid-state tritium NMR analyses of these complexes would provide key distances for determining the expected conformation. Up to now, 2 paclitaxel isotopomers have been prepared from labelling the di-brominated paclitaxel precursor and from coupling the tritiated taxane rings and the tritiated side chains, respectively. The synthetic strategy allowed us to realize the syntheses in generally high yield and good stereoselectivity. Different tritiation methods have been used, from which an isotopic enrichment of higher than 92% was obtained. The syntheses of other 4 isotopomers, together with the microtubule complexes are currently underway in our lab. (author) [fr

  4. Conformal Tachyons

    CERN Document Server

    Tomaschitz, R

    2000-01-01

    We study tachyons conformally coupled to the background geometry of a Milne universe. The causality of superluminal signal transfer is scrutinized in this context. The cosmic time of the comoving frame determines a distinguished time order for events connected by superluminal signals. An observer can relate his rest frame to the galaxy frame, and compare so the time order of events in his proper time to the cosmic time order. All observers can in this way arrive at identical conclusions on the causality of events connected by superluminal signals. An unambiguous energy concept for tachyonic rays is defined by means of the cosmic time of the comoving reference frame, without resorting to an antiparticle interpretation. On that basis we give an explicit proof that no signals can be sent into the past of observers. Causality violating signals are energetically forbidden, as they would have negative energy in the rest frame of the emitting observer. If an observer emits a superluminal signal, the tachyonic respon...

  5. Environmental quenching and galactic conformity in the galaxy cross-correlation signal

    Science.gov (United States)

    Hatfield, P. W.; Jarvis, M. J.

    2017-12-01

    It has long been known that environment has a large effect on star formation in galaxies. There are several known plausible mechanisms to remove the cool gas needed for star formation, such as strangulation, harassment and ram-pressure stripping. It is unclear which process is dominant, and over what range of stellar mass. In this paper, we find evidence for suppression of the cross-correlation function between massive galaxies and less massive star-forming galaxies, giving a measure of how less likely a galaxy is to be star forming in the vicinity of a more massive galaxy. We develop a formalism for modelling environmental quenching mechanisms within the halo occupation distribution scheme. We find that at z ∼ 2 environment is not a significant factor in determining quenching of star-forming galaxies, and that galaxies are quenched with similar probabilities when they are satellites in sub-group environments, as they are globally. However, by z ∼ 0.5 galaxies are much less likely to be star forming when in a high-density (group or low-mass cluster) environment than when not. This increased probability of being quenched does not appear to have significant radial dependence within the halo at lower redshifts, supportive of the quenching being caused by the halting of fresh inflows of pristine gas, as opposed to by tidal stripping. Furthermore, by separating the massive sample into passive and star forming, we see that this effect is further enhanced when the central galaxy is passive, a manifestation of galactic conformity.

  6. Sex determining signal in Drosophila melanogaster

    Indian Academy of Sciences (India)

    Administrator

    Addition of almost any segment of the X chromosome pro- duced a shift towards ... It is now well established that the X/A signal acts to set the functional state ... tionally related because a defect in one of them can be partly. COMMENTARY ON ...

  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

    Based on a rare, natural Glu for Ala204(C+6) variant located six residues after the conserved Cys residue in extracellular loop 2 (ECL2b) associated with selective elimination of the high constitutive signaling of the ghrelin receptor, this loop was subjected to a detailed structure functional....... 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. Alternative method for determining the constant offset in lidar signal

    Science.gov (United States)

    Vladimir A. Kovalev; Cyle Wold; Alexander Petkov; Wei Min Hao

    2009-01-01

    We present an alternative method for determining the total offset in lidar signal created by a daytime background-illumination component and electrical or digital offset. Unlike existing techniques, here the signal square-range-correction procedure is initially performed using the total signal recorded by lidar, without subtraction of the offset component. While...

  9. Nonlocality, no-signalling, and Bellʼs theorem investigated by Weyl conformal differential geometry

    Science.gov (United States)

    De Martini, Francesco; Santamato, Enrico

    2014-12-01

    The principles and methods of conformal quantum geometrodynamics based on Weyl differential geometry are presented. The theory applied to the case of the relativistic single quantum spin-\\frac{1}{2} leads to a novel and unconventional derivation of the Dirac equation. The further extension of the theory to the case of two-spins-\\frac{1}{2} in the EPR entangled state and to the related violation of Bell inequalities leads, by an exact non-relativistic analysis, to an insightful resolution of all paradoxes implied by quantum nonlocality.

  10. Nonlocality, no-signalling, and Bell's theorem investigated by Weyl conformal differential geometry

    International Nuclear Information System (INIS)

    Martini, Francesco De; Santamato, Enrico

    2014-01-01

    The principles and methods of conformal quantum geometrodynamics based on Weyl differential geometry are presented. The theory applied to the case of the relativistic single quantum spin-(1/2) leads to a novel and unconventional derivation of the Dirac equation. The further extension of the theory to the case of two-spins-(1/2) in the EPR entangled state and to the related violation of Bell inequalities leads, by an exact non-relativistic analysis, to an insightful resolution of all paradoxes implied by quantum nonlocality. (paper)

  11. Low-Frequency Beacon Signal Strength Determination.

    Science.gov (United States)

    1980-01-01

    Radio Frequency List , RIS AF-6050-12 [141. Using this value and assum- ing performance for these facilities as indicatcd in FAA Handbook 6050.10, ERP...FAA Handbook 6050. 10 for facilities of appropriate transmitter power, determined from FAA Master Radio Frequency List 6050-12, April 1979...these facilities has not been directly measured and, therefore, values corresponding to transmitter powers given in FAA Master Radio Frequency List , RIS

  12. A precise determination of the psibar-psi anomalous dimension in conformal gauge theories

    CERN Document Server

    Patella, Agostino

    2012-01-01

    A strategy for computing the psibar-psi anomalous dimension at the fixed point in infrared-conformal gauge theories from lattice simulations is discussed. The method is based on the scaling of the spectral density of the Dirac operator or rather its integral, the mode number. It is relatively cheap, mainly for two reasons: (a) the mode number can be determined with quite high accuracy, (b) the psibar-psi anomalous dimension is extracted from a fit of several observables on the same set of configurations (no scaling in the Lagrangian parameters is needed). As an example the psibar-psi anomalous dimension has been computed in the SU(2) theory with 2 Dirac fermions in the adjoint representation of the gauge group, and has been found to be 0.371(20). In this particular case, the proposed strategy has proved to be very robust and effective.

  13. Defining a conformational consensus motif in cotransin-sensitive signal sequences: a proteomic and site-directed mutagenesis study.

    Directory of Open Access Journals (Sweden)

    Wolfgang Klein

    Full Text Available The cyclodepsipeptide cotransin was described to inhibit the biosynthesis of a small subset of proteins by a signal sequence-discriminatory mechanism at the Sec61 protein-conducting channel. However, it was not clear how selective cotransin is, i.e. how many proteins are sensitive. Moreover, a consensus motif in signal sequences mediating cotransin sensitivity has yet not been described. To address these questions, we performed a proteomic study using cotransin-treated human hepatocellular carcinoma cells and the stable isotope labelling by amino acids in cell culture technique in combination with quantitative mass spectrometry. We used a saturating concentration of cotransin (30 micromolar to identify also less-sensitive proteins and to discriminate the latter from completely resistant proteins. We found that the biosynthesis of almost all secreted proteins was cotransin-sensitive under these conditions. In contrast, biosynthesis of the majority of the integral membrane proteins was cotransin-resistant. Cotransin sensitivity of signal sequences was neither related to their length nor to their hydrophobicity. Instead, in the case of signal anchor sequences, we identified for the first time a conformational consensus motif mediating cotransin sensitivity.

  14. Defining a Conformational Consensus Motif in Cotransin-Sensitive Signal Sequences: A Proteomic and Site-Directed Mutagenesis Study

    Science.gov (United States)

    Klein, Wolfgang; Westendorf, Carolin; Schmidt, Antje; Conill-Cortés, Mercè; Rutz, Claudia; Blohs, Marcus; Beyermann, Michael; Protze, Jonas; Krause, Gerd; Krause, Eberhard; Schülein, Ralf

    2015-01-01

    The cyclodepsipeptide cotransin was described to inhibit the biosynthesis of a small subset of proteins by a signal sequence-discriminatory mechanism at the Sec61 protein-conducting channel. However, it was not clear how selective cotransin is, i.e. how many proteins are sensitive. Moreover, a consensus motif in signal sequences mediating cotransin sensitivity has yet not been described. To address these questions, we performed a proteomic study using cotransin-treated human hepatocellular carcinoma cells and the stable isotope labelling by amino acids in cell culture technique in combination with quantitative mass spectrometry. We used a saturating concentration of cotransin (30 micromolar) to identify also less-sensitive proteins and to discriminate the latter from completely resistant proteins. We found that the biosynthesis of almost all secreted proteins was cotransin-sensitive under these conditions. In contrast, biosynthesis of the majority of the integral membrane proteins was cotransin-resistant. Cotransin sensitivity of signal sequences was neither related to their length nor to their hydrophobicity. Instead, in the case of signal anchor sequences, we identified for the first time a conformational consensus motif mediating cotransin sensitivity. PMID:25806945

  15. The conformational and subcellular compartmental dance of plant NLRs during viral recognition and defense signaling

    Science.gov (United States)

    Padmanabhan, Meenu S; Dinesh-Kumar, Savithramma P

    2014-01-01

    Plant innate immune response against viruses utilizes intracellular Nucleotide Binding domain Leucine Rich Repeat (NLR) class of receptors. NLRs recognize different viral proteins termed elicitors and initiate diverse signaling processes that induce programmed cell death (PCD) in infected cells and restrict virus spread. In this review we describe the recent advances made in the study of plant NLRs that detect viruses. We describe some of the physical and functional interactions these NLRs undertake. We elaborate on the intra-molecular and homotypic association of NLRs that function in self-regulation and activation. Nuclear role for some viral NLRs is discussed as well as the emerging importance of the RNAi pathway in regulating the NLR family. PMID:24906192

  16. Solution conformation of the antitumor antibiotic chromomycin A3 determined by two-dimensional NMR spectroscopy

    International Nuclear Information System (INIS)

    Kam, M.; Shafer, R.H.; Berman, E.

    1988-01-01

    A conformational analysis and a complete assignment of the nonexchangeable proton resonances of chromomycin A 3 , dechromose-A chromomycin A 3 , and deacetylchromose-B chromomycin A 3 were carried out in organic solvents. The resulting conformation in methanol has the three side chains of chromomycin A 3 fully extended, away from one another and from the aglycon. In dichloromethane on the other hand, the drug was shown to adopt a highly compact conformation in which most of the 26 oxygen atoms in the molecule point out toward the solvent. The two carbohydrate side chains extend parallel to each other on the same side of the aglycon. Two intramolecular nuclear Overhauser enhancement contacts have been observed between different sugar units on these side chains, indicating close proximity for these moieties. In addition, the aliphatic side chain is folded toward the aglycon, parallel to the two oligosaccharide side chains. The overall conformation has a wedge-like shape with the two phenoxy groups exposed at the pointed edge. The presence of some exchange cross-peaks in the NOESY spectra suggests the presence of intramolecular hydrogen bonds that probably help to maintain the compact information. The derivatives of chromomycin A 3 have qualitatively similar conformations, though their respective conformations are not as compact as the parent drug. The significance of these results is discussed in terms of a model of chromomycin A 3 binding to DNA in the major groove

  17. Conformal Dimensions via Large Charge Expansion.

    Science.gov (United States)

    Banerjee, Debasish; Chandrasekharan, Shailesh; Orlando, Domenico

    2018-02-09

    We construct an efficient Monte Carlo algorithm that overcomes the severe signal-to-noise ratio problems and helps us to accurately compute the conformal dimensions of large-Q fields at the Wilson-Fisher fixed point in the O(2) universality class. Using it, we verify a recent proposal that conformal dimensions of strongly coupled conformal field theories with a global U(1) charge can be obtained via a series expansion in the inverse charge 1/Q. We find that the conformal dimensions of the lowest operator with a fixed charge Q are almost entirely determined by the first few terms in the series.

  18. Solution conformation of 2-aminopurine dinucleotide determined by ultraviolet two-dimensional fluorescence spectroscopy

    International Nuclear Information System (INIS)

    Widom, Julia R; Marcus, Andrew H; Johnson, Neil P; Von Hippel, Peter H

    2013-01-01

    We have observed the conformation-dependent electronic coupling between the monomeric subunits of a dinucleotide of 2-aminopurine (2-AP), a fluorescent analogue of the nucleic acid base adenine. This was accomplished by extending two-dimensional fluorescence spectroscopy (2D FS)—a fluorescence-detected variation of 2D electronic spectroscopy—to excite molecular transitions in the ultraviolet (UV) regime. A collinear sequence of four ultrafast laser pulses centered at 323 nm was used to resonantly excite the coupled transitions of 2-AP dinucleotide. The phases of the optical pulses were continuously swept at kilohertz frequencies, and the ensuing nonlinear fluorescence was phase-synchronously detected at 370 nm. Upon optimization of a point–dipole coupling model to our data, we found that in aqueous buffer the 2-AP dinucleotide adopts an average conformation in which the purine bases are non-helically stacked (center-to-center distance R 12 = 3.5 ± 0.5 Å , twist angle θ 12 = 5° ± 5° ), which differs from the conformation of such adjacent bases in duplex DNA. These experiments establish UV–2D FS as a method for examining the local conformations of an adjacent pair of fluorescent nucleotides substituted into specific DNA or RNA constructs, which will serve as a powerful probe to interpret, in structural terms, biologically significant local conformational changes within the nucleic acid framework of protein–nucleic acid complexes. (paper)

  19. Code conforming determination of cumulative usage factors for general elastic-plastic finite element analyses

    International Nuclear Information System (INIS)

    Rudolph, Juergen; Goetz, Andreas; Hilpert, Roland

    2012-01-01

    The procedures of fatigue analyses of several relevant nuclear and conventional design codes (ASME, KTA, EN, AD) for power plant components differentiate between an elastic, simplified elastic-plastic and elastic-plastic fatigue check. As a rule, operational load levels will exclude the purely elastic fatigue check. The application of the code procedure of the simplified elastic-plastic fatigue check is common practice. Nevertheless, resulting cumulative usage factors may be overly conservative mainly due to high code based plastification penalty factors Ke. As a consequence, the more complex and still code conforming general elastic-plastic fatigue analysis methodology based on non-linear finite element analysis (FEA) is applied for fatigue design as an alternative. The requirements of the FEA and the material law to be applied have to be clarified in a first step. Current design codes only give rough guidelines on these relevant items. While the procedure for the simplified elastic-plastic fatigue analysis and the associated code passages are based on stress related cycle counting and the determination of pseudo elastic equivalent stress ranges, an adaptation to elastic-plastic strains and strain ranges is required for the elastic-plastic fatigue check. The associated requirements are explained in detail in the paper. If the established and implemented evaluation mechanism (cycle counting according to the peak and valley respectively the rainflow method, calculation of stress ranges from arbitrary load-time histories and determination of cumulative usage factors based on all load events) is to be retained, a conversion of elastic-plastic strains and strain ranges into pseudo elastic stress ranges is required. The algorithm to be applied is described in the paper. It has to be implemented in the sense of an extended post processing operation of FEA e.g. by APDL scripts in ANSYS registered . Variations of principal stress (strain) directions during the loading

  20. Conformational Flexibility Determines Selectivity and Antibacterial, Antiplasmodial, and Anticancer Potency of Cationic α-Helical Peptides*

    OpenAIRE

    Vermeer, Louic S.; Lan, Yun; Abbate, Vincenzo; Ruh, Emrah; Bui, Tam T.; Wilkinson, Louise J.; Kanno, Tokuwa; Jumagulova, Elmira; Kozlowska, Justyna; Patel, Jayneil; McIntyre, Caitlin A.; Yam, W. C.; Siu, Gilman; Atkinson, R. Andrew; Lam, Jenny K. W.

    2012-01-01

    Background: Antimicrobial peptides (AMPs) have the potential to act against multiple pathogenic targets. Results: AMPs that maintain conformational flexibility are more potent against multiple pathogens and less hemolytic. Conclusion: Antimicrobial action and hemolysis proceed via differing mechanisms. Significance: The potency, selectivity, and ability of AMPs to reach intracellular pathogens can be modulated using general principles.

  1. Protein energetic conformational analysis from NMR chemical shifts (PECAN) and its use in determining secondary structural elements

    Energy Technology Data Exchange (ETDEWEB)

    Eghbalnia, Hamid R.; Wang Liya; Bahrami, Arash [National Magnetic Resonance Facility at Madison, Biochemistry Department (United States); Assadi, Amir [University of Wisconsin-Madison, Mathematics Department (United States); Markley, John L. [National Magnetic Resonance Facility at Madison, Biochemistry Department (United States)], E-mail: eghbalni@nmrfam.wisc.edu

    2005-05-15

    We present an energy model that combines information from the amino acid sequence of a protein and available NMR chemical shifts for the purposes of identifying low energy conformations and determining elements of secondary structure. The model ('PECAN', Protein Energetic Conformational Analysis from NMR chemical shifts) optimizes a combination of sequence information and residue-specific statistical energy function to yield energetic descriptions most favorable to predicting secondary structure. Compared to prior methods for secondary structure determination, PECAN provides increased accuracy and range, particularly in regions of extended structure. Moreover, PECAN uses the energetics to identify residues located at the boundaries between regions of predicted secondary structure that may not fit the stringent secondary structure class definitions. The energy model offers insights into the local energetic patterns that underlie conformational preferences. For example, it shows that the information content for defining secondary structure is localized about a residue and reaches a maximum when two residues on either side are considered. The current release of the PECAN software determines the well-defined regions of secondary structure in novel proteins with assigned chemical shifts with an overall accuracy of 90%, which is close to the practical limit of achievable accuracy in classifying the states.

  2. Protein energetic conformational analysis from NMR chemical shifts (PECAN) and its use in determining secondary structural elements

    International Nuclear Information System (INIS)

    Eghbalnia, Hamid R.; Wang Liya; Bahrami, Arash; Assadi, Amir; Markley, John L.

    2005-01-01

    We present an energy model that combines information from the amino acid sequence of a protein and available NMR chemical shifts for the purposes of identifying low energy conformations and determining elements of secondary structure. The model ('PECAN', Protein Energetic Conformational Analysis from NMR chemical shifts) optimizes a combination of sequence information and residue-specific statistical energy function to yield energetic descriptions most favorable to predicting secondary structure. Compared to prior methods for secondary structure determination, PECAN provides increased accuracy and range, particularly in regions of extended structure. Moreover, PECAN uses the energetics to identify residues located at the boundaries between regions of predicted secondary structure that may not fit the stringent secondary structure class definitions. The energy model offers insights into the local energetic patterns that underlie conformational preferences. For example, it shows that the information content for defining secondary structure is localized about a residue and reaches a maximum when two residues on either side are considered. The current release of the PECAN software determines the well-defined regions of secondary structure in novel proteins with assigned chemical shifts with an overall accuracy of 90%, which is close to the practical limit of achievable accuracy in classifying the states

  3. Determination of alpha(s)(M(tau)(2)): conformal mapping approach

    Czech Academy of Sciences Publication Activity Database

    Caprini, I.; Fischer, Jan

    2011-01-01

    Roč. 218, - (2011), s. 128-133 ISSN 0920-5632. [11th International Workshop on Tau Lepton Physics. Manchester, 13.09.2010-17.09.2010] R&D Projects: GA MŠk LC527; GA MŠk LA08015 Institutional research plan: CEZ:AV0Z10100502 Keywords : perturbative QCD expansion * conformal mapping * hadronic decay of the tau lepton Subject RIV: BF - Elementary Particles and High Energy Physics

  4. Interaction Dynamics Determine Signaling and Output Pathway Responses

    Directory of Open Access Journals (Sweden)

    Klement Stojanovski

    2017-04-01

    Full Text Available The understanding of interaction dynamics in signaling pathways can shed light on pathway architecture and provide insights into targets for intervention. Here, we explored the relevance of kinetic rate constants of a key upstream osmosensor in the yeast high-osmolarity glycerol-mitogen-activated protein kinase (HOG-MAPK pathway to signaling output responses. We created mutant pairs of the Sln1-Ypd1 complex interface that caused major compensating changes in the association (kon and dissociation (koff rate constants (kinetic perturbations but only moderate changes in the overall complex affinity (Kd. Yeast cells carrying a Sln1-Ypd1 mutant pair with moderate increases in kon and koff displayed a lower threshold of HOG pathway activation than wild-type cells. Mutants with higher kon and koff rates gave rise to higher basal signaling and gene expression but impaired osmoadaptation. Thus, the kon and koff rates of the components in the Sln1 osmosensor determine proper signaling dynamics and osmoadaptation.

  5. AN ATTEMPT TO DETERMINE THE RELATION BETWEEN HUCUL HORSES CONFORMATION ASSESSMENT, MOVEMENT AND COURAGE TEST RESULTS PART II. MARE FAMILIES

    Directory of Open Access Journals (Sweden)

    Jadwiga TOPCZEWSKA

    2012-01-01

    Full Text Available The objective of the research was to determine the relationship between evaluation of conformation and motion indicators and results of the Huculs’ path and also to ascertain the courage (basic and elimination of Hucul horses with their classification into mare families being taken account of. The scores of 116 horses presented for the evaluation of their exterior (championship breeding were analyzed. The assessment covered the type, body conformation, movement in walk and trot as well as overall impression and preparedness for the exhibition. Measurements of length of steps, frequency and rate of the walk and trot were performed during the tests for courage. The estimated correlation coefficients exhibited the existence of some interesting trends i.e., there was positive correlation between values for type, body conformation, movement in walk and trot and the length of steps in walk and trot in individuals representing most of mare families. The reverse was the case with horses from the Sroczka and Wyderka families. Amongst the Wrona, however, negative correlations between the grade for walk and frequency of steps in walk was observed while that of between the result of path and utility tests was positive.

  6. Spectroscopic determination of lysozyme conformational changes in the presence of trehalose and guanidine.

    Science.gov (United States)

    Barreca, Davide; Laganà, Giuseppina; Ficarra, Silvana; Gattuso, Giuseppe; Magazù, Salvatore; La Torre, Roberto; Tellone, Ester; Bellocco, Ersilia

    2013-06-01

    The bioprotective action of the disaccharide trehalose has been studied against the well-known denaturating agent, guanidine hydrochloride. The results indicated a direct influence of trehalose on both enzymatic activity and conformational changes of lysozyme, as shown by the decrease of the inactivation rate constant of about 1.48-fold and the loss of α-helix structure of lysozyme. In addition, ESI-MS hydrogen-deuterium (H/D) exchange experiments allowed us to correlate the structural and dynamic features of the protein in the presence of the two additives, highlighting as trehalose remarkably influenced this exchange by decreasing local protein environment changes and solvent accessibility to the amide peptide backbone, as further evidenced by circular dichroism and (1)H NMR measurements.

  7. Determination of a PWR key neutron parameters uncertainties and conformity studies applications

    International Nuclear Information System (INIS)

    Bernard, D.

    2002-01-01

    The aim of this thesis was to evaluate uncertainties of key neutron parameters of slab reactors. Uncertainties sources have many origins, technologic origin for parameters of fabrication and physical origin for nuclear data. First, each contribution of uncertainties is calculated and finally, a factor of uncertainties is associated to key slab parameter like reactivity, isotherm reactivity coefficient, control rod efficiency, power form factor before irradiation and lifetime. This factors of uncertainties were computed by Generalized Perturbations Theory in case of step 0 and by directs calculations in case of irradiation problems. One of neutronic conformity applications was about fabrication and nuclear data targets precision adjustments. Statistic (uncertainties) and deterministic (deviations) approaches were studied. Then neutronics key slab parameters uncertainties were reduced and so nuclear performances were optimised. (author)

  8. Specific Stereoisomeric Conformations Determine the Drug Potency of Cladosporin Scaffold against Malarial Parasite.

    Science.gov (United States)

    Das, Pronay; Babbar, Palak; Malhotra, Nipun; Sharma, Manmohan; Jachak, Gorakhnath R; Gonnade, Rajesh G; Shanmugam, Dhanasekaran; Harlos, Karl; Yogavel, Manickam; Sharma, Amit; Reddy, D Srinivasa

    2018-05-21

    The dependence of drug potency on diastereomeric configurations is a key facet. Using a novel general divergent synthetic route for a three-chiral centre anti-malarial natural product cladosporin, we built its complete library of stereoisomers (cladologs) and assessed their inhibitory potential using parasite-, enzyme- and structure-based assays. We show that potency is manifest via tetrahyropyran ring conformations that are housed in the ribose binding pocket of parasite lysyl tRNA synthetase (KRS). Strikingly, drug potency between top and worst enantiomers varied 500-fold, and structures of KRS-cladolog complexes reveal that alterations at C3 and C10 are detrimental to drug potency where changes at C3 are sensed by rotameric flipping of Glutamate332. Given that scores of anti-malarial and anti-infective drugs contain chiral centers, this work provides a new foundation for focusing on inhibitor stereochemistry as a facet of anti-microbial drug development.

  9. Determination of the populations and structures of multiple conformers in an ensemble from NMR data: Multiple-copy refinement of nucleic acid structures using floating weights

    International Nuclear Information System (INIS)

    Goerler, Adrian; Ulyanov, Nikolai B.; James, Thomas L.

    2000-01-01

    A new algorithm is presented for determination of structural conformers and their populations based on NMR data. Restrained Metropolis Monte Carlo simulations or restrained energy minimizations are performed for several copies of a molecule simultaneously. The calculations are restrained with dipolar relaxation rates derived from measured NOE intensities via complete relaxation matrix analysis. The novel feature of the algorithm is that the weights of individual conformers are determined in every refinement step, by the quadratic programming algorithm, in such a way that the restraint energy is minimized. Its design ensures that the calculated populations of the individual conformers are based only on experimental restraints. Presence of internally inconsistent restraints is the driving force for determination of distinct multiple conformers. The method is applied to various simulated test systems. Conformational calculations on nucleic acids are carried out using generalized helical parameters with the program DNAminiCarlo. From different mixtures of A- and B-DNA, minor fractions as low as 10% could be determined with restrained energy minimization. For B-DNA with three local conformers (C2'-endo, O4'-exo, C3'-endo), the minor O4'-exo conformer could not be reliably determined using NOE data typically measured for DNA. The other two conformers, C2'-endo and C3'-endo, could be reproduced by Metropolis Monte Carlo simulated annealing. The behavior of the algorithm in various situations is analyzed, and a number of refinement protocols are discussed. Prior to application of this algorithm to each experimental system, it is suggested that the presence of internal inconsistencies in experimental data be ascertained. In addition, because the performance of the algorithm depends on the type of conformers involved and experimental data available, it is advisable to carry out test calculations with simulated data modeling each experimental system studied

  10. Steric exclusion and protein conformation determine the localization of plasma membrane transporters.

    Science.gov (United States)

    Bianchi, Frans; Syga, Łukasz; Moiset, Gemma; Spakman, Dian; Schavemaker, Paul E; Punter, Christiaan M; Seinen, Anne-Bart; van Oijen, Antoine M; Robinson, Andrew; Poolman, Bert

    2018-02-05

    The plasma membrane (PM) of Saccharomyces cerevisiae contains membrane compartments, MCC/eisosomes and MCPs, named after the protein residents Can1 and Pma1, respectively. Using high-resolution fluorescence microscopy techniques we show that Can1 and the homologous transporter Lyp1 are able to diffuse into the MCC/eisosomes, where a limited number of proteins are conditionally trapped at the (outer) edge of the compartment. Upon addition of substrate, the immobilized proteins diffuse away from the MCC/eisosomes, presumably after taking a different conformation in the substrate-bound state. Our data indicate that the mobile fraction of all integral plasma membrane proteins tested shows extremely slow Brownian diffusion through most of the PM. We also show that proteins with large cytoplasmic domains, such as Pma1 and synthetic chimera of Can1 and Lyp1, are excluded from the MCC/eisosomes. We hypothesize that the distinct localization patterns found for these integral membrane proteins in S. cerevisiae arises from a combination of slow lateral diffusion, steric exclusion, and conditional trapping in membrane compartments.

  11. Selection and determination of beam weights based on genetic algorithms for conformal radiotherapy treatment planning

    International Nuclear Information System (INIS)

    Xingen Wu; Zunliang Wang

    2000-01-01

    A genetic algorithm has been used to optimize the selection of beam weights for external beam three-dimensional conformal radiotherapy treatment planning. A fitness function is defined, which includes a difference function to achieve a least-square fit to doses at preselected points in a planning target volume, and a penalty item to constrain the maximum allowable doses delivered to critical organs. Adjustment between the dose uniformity within the target volume and the dose constraint to the critical structures can be achieved by varying the beam weight variables in the fitness function. A floating-point encoding schema and several operators, like uniform crossover, arithmetical crossover, geometrical crossover, Gaussian mutation and uniform mutation, have been used to evolve the population. Three different cases were used to verify the correctness of the algorithm and quality assessment based on dose-volume histograms and three-dimensional dose distributions were given. The results indicate that the genetic algorithm presented here has considerable potential. (author)

  12. Conformational Flexibility Determines Selectivity and Antibacterial, Antiplasmodial, and Anticancer Potency of Cationic α-Helical Peptides*

    Science.gov (United States)

    Vermeer, Louic S.; Lan, Yun; Abbate, Vincenzo; Ruh, Emrah; Bui, Tam T.; Wilkinson, Louise J.; Kanno, Tokuwa; Jumagulova, Elmira; Kozlowska, Justyna; Patel, Jayneil; McIntyre, Caitlin A.; Yam, W. C.; Siu, Gilman; Atkinson, R. Andrew; Lam, Jenny K. W.; Bansal, Sukhvinder S.; Drake, Alex F.; Mitchell, Graham H.; Mason, A. James

    2012-01-01

    We used a combination of fluorescence, circular dichroism (CD), and NMR spectroscopies in conjunction with size exclusion chromatography to help rationalize the relative antibacterial, antiplasmodial, and cytotoxic activities of a series of proline-free and proline-containing model antimicrobial peptides (AMPs) in terms of their structural properties. When compared with proline-free analogs, proline-containing peptides had greater activity against Gram-negative bacteria, two mammalian cancer cell lines, and intraerythrocytic Plasmodium falciparum, which they were capable of killing without causing hemolysis. In contrast, incorporation of proline did not have a consistent effect on peptide activity against Mycobacterium tuberculosis. In membrane-mimicking environments, structures with high α-helix content were adopted by both proline-free and proline-containing peptides. In solution, AMPs generally adopted disordered structures unless their sequences comprised more hydrophobic amino acids or until coordinating phosphate ions were added. Proline-containing peptides resisted ordering induced by either method. The roles of the angle subtended by positively charged amino acids and the positioning of the proline residues were also investigated. Careful positioning of proline residues in AMP sequences is required to enable the peptide to resist ordering and maintain optimal antibacterial activity, whereas varying the angle subtended by positively charged amino acids can attenuate hemolytic potential albeit with a modest reduction in potency. Maintaining conformational flexibility improves AMP potency and selectivity toward bacterial, plasmodial, and cancerous cells while enabling the targeting of intracellular pathogens. PMID:22869378

  13. Conformational Entropy of FK506 Binding to FKBP12 Determined by Nuclear Magnetic Resonance Relaxation and Molecular Dynamics Simulations.

    Science.gov (United States)

    Solomentsev, Gleb; Diehl, Carl; Akke, Mikael

    2018-03-06

    FKBP12 (FK506 binding protein 12 kDa) is an important drug target. Nuclear magnetic resonance (NMR) order parameters, describing amplitudes of motion on the pico- to nanosecond time scale, can provide estimates of changes in conformational entropy upon ligand binding. Here we report backbone and methyl-axis order parameters of the apo and FK506-bound forms of FKBP12, based on 15 N and 2 H NMR relaxation. Binding of FK506 to FKBP12 results in localized changes in order parameters, notably for the backbone of residues E54 and I56 and the side chains of I56, I90, and I91, all positioned in the binding site. The order parameters increase slightly upon FK506 binding, indicating an unfavorable entropic contribution to binding of TΔ S = -18 ± 2 kJ/mol at 293 K. Molecular dynamics simulations indicate a change in conformational entropy, associated with all dihedral angles, of TΔ S = -26 ± 9 kJ/mol. Both these values are significant compared to the total entropy of binding determined by isothermal titration calorimetry and referenced to a reactant concentration of 1 mM ( TΔ S = -29 ± 1 kJ/mol). Our results reveal subtle differences in the response to ligand binding compared to that of the previously studied rapamycin-FKBP12 complex, despite the high degree of structural homology between the two complexes and their nearly identical ligand-FKBP12 interactions. These results highlight the delicate dependence of protein dynamics on drug interactions, which goes beyond the view provided by static structures, and reinforce the notion that protein conformational entropy can make important contributions to the free energy of ligand binding.

  14. Determination of signal intensity affected by Gaussian noise

    International Nuclear Information System (INIS)

    Blostein, Jeronimo J.; Bennun, Leonardo

    1999-01-01

    A methodology based on maximum likelihood criteria, to identify and quantify an arbitrary signal affected by Gaussian noise is shown. To use this methodology it is necessary to know the position in the spectrum where the signal of interest should appear, and the shape of the signal when the background is null or unappreciable. (author)

  15. Using 1H and 13C NMR chemical shifts to determine cyclic peptide conformations: a combined molecular dynamics and quantum mechanics approach.

    Science.gov (United States)

    Nguyen, Q Nhu N; Schwochert, Joshua; Tantillo, Dean J; Lokey, R Scott

    2018-05-10

    Solving conformations of cyclic peptides can provide insight into structure-activity and structure-property relationships, which can help in the design of compounds with improved bioactivity and/or ADME characteristics. The most common approaches for determining the structures of cyclic peptides are based on NMR-derived distance restraints obtained from NOESY or ROESY cross-peak intensities, and 3J-based dihedral restraints using the Karplus relationship. Unfortunately, these observables are often too weak, sparse, or degenerate to provide unequivocal, high-confidence solution structures, prompting us to investigate an alternative approach that relies only on 1H and 13C chemical shifts as experimental observables. This method, which we call conformational analysis from NMR and density-functional prediction of low-energy ensembles (CANDLE), uses molecular dynamics (MD) simulations to generate conformer families and density functional theory (DFT) calculations to predict their 1H and 13C chemical shifts. Iterative conformer searches and DFT energy calculations on a cyclic peptide-peptoid hybrid yielded Boltzmann ensembles whose predicted chemical shifts matched the experimental values better than any single conformer. For these compounds, CANDLE outperformed the classic NOE- and 3J-coupling-based approach by disambiguating similar β-turn types and also enabled the structural elucidation of the minor conformer. Through the use of chemical shifts, in conjunction with DFT and MD calculations, CANDLE can help illuminate conformational ensembles of cyclic peptides in solution.

  16. 40 CFR 93.106 - Content of transportation plans and timeframe of conformity determinations.

    Science.gov (United States)

    2010-07-01

    ... transportation analysis in use by the MPO. Transit facilities, equipment, and services envisioned for the future... plans which meet those requirements. Otherwise, the transportation system envisioned for the future must... determination; (iv) The last year of the transportation plan's forecast period must be a horizon year; and (v...

  17. Determination of conformation and orientation of immobilized peptides and proteins at buried interfaces

    Science.gov (United States)

    Shen, Lei; Ulrich, Nathan W.; Mello, Charlene M.; Chen, Zhan

    2015-01-01

    Surface immobilized peptides/proteins have important applications such as antimicrobial coating and biosensing. We report a study of such peptides/proteins using sum frequency generation vibrational spectroscopy and ATR-FTIR. Immobilization on surfaces via physical adsorption and chemical coupling revealed that structures of chemically immobilized peptides are determined by immobilization sites, chemical environments, and substrate surfaces. In addition, controlling enzyme orientation by engineering the surface immobilization site demonstrated that structures can be well-correlated to measured chemical activity. This research facilitates the development of immobilized peptides/proteins with improved activities by optimizing their surface orientation and structure.

  18. Protein Conformation Ensembles Monitored by HDX Reveal a Structural Rationale for Abscisic Acid Signaling Protein Affinities and Activities

    OpenAIRE

    West, Graham M.; Pascal, Bruce D.; Ng, Ley-Moy; Soon, Fen-Fen; Melcher, Karsten; Xu, H. Eric; Chalmers, Michael J.; Griffin, Patrick R.

    2013-01-01

    Plants regulate growth and respond to environmental stress through abscisic acid (ABA) regulated pathways, and as such these pathways are of primary interest for biological and agricultural research. The ABA response is first perceived by the PYR/PYL/RCAR class of START protein receptors. These ABA activated receptors disrupt phosphatase inhibition of Snf1-related kinases (SnRKs) enabling kinase signaling. Here, insights into the structural mechanism of proteins in the ABA signaling pathway (...

  19. Conformal Nets II: Conformal Blocks

    Science.gov (United States)

    Bartels, Arthur; Douglas, Christopher L.; Henriques, André

    2017-08-01

    Conformal nets provide a mathematical formalism for conformal field theory. Associated to a conformal net with finite index, we give a construction of the `bundle of conformal blocks', a representation of the mapping class groupoid of closed topological surfaces into the category of finite-dimensional projective Hilbert spaces. We also construct infinite-dimensional spaces of conformal blocks for topological surfaces with smooth boundary. We prove that the conformal blocks satisfy a factorization formula for gluing surfaces along circles, and an analogous formula for gluing surfaces along intervals. We use this interval factorization property to give a new proof of the modularity of the category of representations of a conformal net.

  20. Characterization of molecular determinants of the conformational stability of macrophage migration inhibitory factor: leucine 46 hydrophobic pocket.

    Directory of Open Access Journals (Sweden)

    Farah El-Turk

    Full Text Available Macrophage Migration Inhibitory Factor (MIF is a key mediator of inflammatory responses and innate immunity and has been implicated in the pathogenesis of several inflammatory and autoimmune diseases. The oligomerization of MIF, more specifically trimer formation, is essential for its keto-enol tautomerase activity and probably mediates several of its interactions and biological activities, including its binding to its receptor CD74 and activation of certain signaling pathways. Therefore, understanding the molecular factors governing the oligomerization of MIF and the role of quaternary structure in modulating its structural stability and multifunctional properties is crucial for understanding the function of MIF in health and disease. Herein, we describe highly conserved intersubunit interactions involving the hydrophobic packing of the side chain of Leu46 onto the β-strand β3 of one monomer within a hydrophobic pocket from the adjacent monomer constituted by residues Arg11, Val14, Phe18, Leu19, Val39, His40, Val41, Val42, and Pro43. To elucidate the structural significance of these intersubunit interactions and their relative contribution to MIF's trimerization, structural stability and catalytic activity, we generated three point mutations where Leu46 was replaced by glycine (L46G, alanine (L46A and phenylalanine (L46F, and their structural properties, stability, oligomerization state, and catalytic activity were characterized using a battery of biophysical methods and X-ray crystallography. Our findings provide new insights into the role of the Leu46 hydrophobic pocket in stabilizing the conformational state of MIF in solution. Disrupting the Leu46 hydrophobic interaction perturbs the secondary and tertiary structure of the protein but has no effect on its oligomerization state.

  1. Conformal house

    DEFF Research Database (Denmark)

    Ryttov, Thomas Aaby; Sannino, Francesco

    2010-01-01

    fixed point. As a consistency check we recover the previously investigated bounds of the conformal windows when restricting to a single matter representation. The earlier conformal windows can be imagined to be part now of the new conformal house. We predict the nonperturbative anomalous dimensions...... at the infrared fixed points. We further investigate the effects of adding mass terms to the condensates on the conformal house chiral dynamics and construct the simplest instanton induced effective Lagrangian terms...

  2. Magnetic resonance signal moment determination using the Earth's magnetic field

    KAUST Repository

    Fridjonsson, Einar Orn; Creber, Sarah A.; Vrouwenvelder, Johannes S.; Johns, Michael L.

    2015-01-01

    We demonstrate a method to manipulate magnetic resonance data such that the moments of the signal spatial distribution are readily accessible. Usually, magnetic resonance imaging relies on data acquired in so-called k-space which is subsequently Fourier transformed to render an image. Here, via analysis of the complex signal in the vicinity of the centre of k-space we are able to access the first three moments of the signal spatial distribution, ultimately in multiple directions. This is demonstrated for biofouling of a reverse osmosis (RO) membrane module, rendering unique information and an early warning of the onset of fouling. The analysis is particularly applicable for the use of mobile magnetic resonance spectrometers; here we demonstrate it using an Earth's magnetic field system.

  3. Magnetic resonance signal moment determination using the Earth's magnetic field

    KAUST Repository

    Fridjonsson, Einar Orn

    2015-03-01

    We demonstrate a method to manipulate magnetic resonance data such that the moments of the signal spatial distribution are readily accessible. Usually, magnetic resonance imaging relies on data acquired in so-called k-space which is subsequently Fourier transformed to render an image. Here, via analysis of the complex signal in the vicinity of the centre of k-space we are able to access the first three moments of the signal spatial distribution, ultimately in multiple directions. This is demonstrated for biofouling of a reverse osmosis (RO) membrane module, rendering unique information and an early warning of the onset of fouling. The analysis is particularly applicable for the use of mobile magnetic resonance spectrometers; here we demonstrate it using an Earth\\'s magnetic field system.

  4. Conformational coupling between receptor and kinase binding sites through a conserved salt bridge in a signaling complex scaffold protein.

    Directory of Open Access Journals (Sweden)

    Davi R Ortega

    Full Text Available Bacterial chemotaxis is one of the best studied signal transduction pathways. CheW is a scaffold protein that mediates the association of the chemoreceptors and the CheA kinase in a ternary signaling complex. The effects of replacing conserved Arg62 of CheW with other residues suggested that the scaffold protein plays a more complex role than simply binding its partner proteins. Although R62A CheW had essentially the same affinity for chemoreceptors and CheA, cells expressing the mutant protein are impaired in chemotaxis. Using a combination of molecular dynamics simulations (MD, NMR spectroscopy, and circular dichroism (CD, we addressed the role of Arg62. Here we show that Arg62 forms a salt bridge with another highly conserved residue, Glu38. Although this interaction is unimportant for overall protein stability, it is essential to maintain the correct alignment of the chemoreceptor and kinase binding sites of CheW. Computational and experimental data suggest that the role of the salt bridge in maintaining the alignment of the two partner binding sites is fundamental to the function of the signaling complex but not to its assembly. We conclude that a key feature of CheW is to maintain the specific geometry between the two interaction sites required for its function as a scaffold.

  5. Theoretical Study of Molecular Determinants Involved in Signal Binding to the TraR Protein of Agrobacterium tumefaciens

    Directory of Open Access Journals (Sweden)

    N. Kumar

    2005-10-01

    Full Text Available N-acylated homoserine lactone (AHL mediated cell-cell communication in bacteria is dependent on the recognition of the cognate signal by its receptor. This interaction allows the receptor-ligand complex to act as a transcriptional activator, controlling the expression of a range of bacterial phenotypes, including virulence factor expression and biofilm formation. One approach to determine the key features of signal- binding is to model the intermolecular interactions between the receptor and ligand using computational-based modeling software (LigandFit. In this communication, we have modeled the crystal structure of the AHL receptor protein TraR and its AHL signal N-(3- oxooctanoyl-homoserine lactone from Agrobacterium tumefaciens and compared it to the previously reported antagonist behaviour of a number of AHL analogues, in an attempt to determine structural constraints for ligand binding. We conclude that (i a common conformation of the AHL in the hydrophobic and hydrophilic region exists for ligand-binding, (ii a tail chain length threshold of 8 carbons is most favourable for ligand-binding affinity, (iii the positive correlation in the docking studies could be used a virtual screening tool.

  6. Determine the Role of Canonical Wnt Signaling in Ovarian Tumorigenesis

    Science.gov (United States)

    2015-12-01

    Cancer Res, 2007. 13(14): p. 4042-5. 10. Mann, B., et al., Target genes of beta-catenin-T cell -factor/ lymphoid -enhancer- factor signaling in human...triggers innate immunity. Cell Host Microbe 12(4): 558–570. 34. Lundholm M, et al. (2014) Prostate tumor-derived exosomes down-regulate NKG2D... cell -extrinsic pathway through which natural killer cells eliminate cancer cells . Nat Cell Biol 15(7):818–828. 57. Ishii KJ, Akira S (2006) Innate

  7. Myosin isoform determines the conformational dynamics and cooperativity of actin filaments in the strongly bound actomyosin complex

    Science.gov (United States)

    Prochniewicz, Ewa; Chin, Harvey F.; Henn, Arnon; Hannemann, Diane E.; Olivares, Adrian O.; Thomas, David D.; De La Cruz, Enrique M.

    2010-01-01

    SUMMARY We have used transient phosphorescence anisotropy (TPA) to detect the microsecond rotational dynamics of erythrosin iodoacetamide (ErIA)-labeled actin strongly bound to single-headed fragments of muscle myosin (muscle S1) and non-muscle myosin V (MV). The conformational dynamics of actin filaments in solution are markedly influenced by the isoform of bound myosin. Both myosins increase the final anisotropy of actin at sub-stoichiometric binding densities, indicating long-range, non-nearest neighbor cooperative restriction of filament rotational dynamics amplitude, but the cooperative unit is larger with MV than muscle S1. Both myosin isoforms also cooperatively affect the actin filament rotational correlation time, but with opposite effects; muscle S1 decreases rates of intrafilament torsional motion, while binding of MV increases the rates of motion. The cooperative effects on the rates of intrafilament motions correlate with the kinetics of myosin binding to actin filaments such that MV binds more rapidly, and muscle myosin more slowly, to partially decorated filaments than to bare filaments. The two isoforms also differ in their effects on the phosphorescence lifetime of the actin-bound ErIA; while muscle S1 increases the lifetime, suggesting decreased aqueous exposure of the probe, MV does not induce a significant change. We conclude that the dynamics and structure of actin in the strongly bound actomyosin complex is determined by the isoform of the bound myosin, in a manner likely to accommodate the diverse functional roles of actomyosin in muscle and non-muscle cells. PMID:19962990

  8. New conformations of linear polyubiquitin chains from crystallographic and solution-scattering studies expand the conformational space of polyubiquitin.

    Science.gov (United States)

    Thach, Trung Thanh; Shin, Donghyuk; Han, Seungsu; Lee, Sangho

    2016-04-01

    The conformational flexibility of linkage-specific polyubiquitin chains enables ubiquitylated proteins and their receptors to be involved in a variety of cellular processes. Linear or Met1-linked polyubiquitin chains, associated with nondegradational cellular signalling pathways, have been known to adopt multiple conformations from compact to extended conformations. However, the extent of such conformational flexibility remains open. Here, the crystal structure of linear Ub2 was determined in a more compact conformation than that of the previously known structure (PDB entry 3axc). The two structures differ significantly from each other, as shown by an r.m.s.d. between C(α) atoms of 3.1 Å. The compactness of the linear Ub2 structure in comparison with PDB entry 3axc is supported by smaller values of the radius of gyration (Rg; 18 versus 18.9 Å) and the maximum interatomic distance (Dmax; 55.5 versus 57.8 Å). Extra intramolecular hydrogen bonds formed among polar residues between the distal and proximal ubiquitin moieties seem to contribute to stabilization of the compact conformation of linear Ub2. An ensemble of three semi-extended and extended conformations of linear Ub2 was also observed by small-angle X-ray scattering (SAXS) analysis in solution. In addition, the conformational heterogeneity in linear polyubiquitin chains is clearly manifested by SAXS analyses of linear Ub3 and Ub4: at least three distinct solution conformations are observed in each chain, with the linear Ub3 conformations being compact. The results expand the extent of conformational space of linear polyubiquitin chains and suggest that changes in the conformational ensemble may be pivotal in mediating multiple signalling pathways.

  9. Transportation Conformity

    Science.gov (United States)

    This section provides information on: current laws, regulations and guidance, policy and technical guidance, project-level conformity, general information, contacts and training, adequacy review of SIP submissions

  10. Determining In Situ Protein Conformation and Orientation from the Amide-I Sum-Frequency Generation Spectrum: Theory and Experiment

    NARCIS (Netherlands)

    Roeters, S.J.; van Dijk, C.N.; Torres Knoop, A.; Backus, E.H.G.; Campen, R.K.; Bonn, M.; Woutersen, S.

    2013-01-01

    Vibrational sum-frequency generation (VSFG) spectra of the amide-I band of proteins can give detailed insight into biomolecular processes near membranes. However, interpreting these spectra in terms of the conformation and orientation of a protein can be difficult, especially in the case of complex

  11. Workers’ Conformism

    Directory of Open Access Journals (Sweden)

    Nikolay Ivantchev

    2013-10-01

    Full Text Available Conformism was studied among 46 workers with different kinds of occupations by means of two modified scales measuring conformity by Santor, Messervey, and Kusumakar (2000 – scale for perceived peer pressure and scale for conformism in antisocial situations. The hypothesis of the study that workers’ conformism is expressed in a medium degree was confirmed partly. More than a half of the workers conform in a medium degree for taking risk, and for the use of alcohol and drugs, and for sexual relationships. More than a half of the respondents conform in a small degree for anti-social activities (like a theft. The workers were more inclined to conform for risk taking (10.9%, then – for the use of alcohol, drugs and for sexual relationships (8.7%, and in the lowest degree – for anti-social activities (6.5%. The workers who were inclined for the use of alcohol and drugs tended also to conform for anti-social activities.

  12. c-Kit signaling determines neointimal hyperplasia in arteriovenous fistulae

    Science.gov (United States)

    Skartsis, Nikolaos; Martinez, Laisel; Duque, Juan Camilo; Tabbara, Marwan; Velazquez, Omaida C.; Asif, Arif; Andreopoulos, Fotios; Salman, Loay H.

    2014-01-01

    Stenosis of arteriovenous (A-V) fistulae secondary to neointimal hyperplasia (NIH) compromises dialysis delivery, which worsens patients' quality of life and increases medical costs associated with the maintenance of vascular accesses. In the present study, we evaluated the role of the receptor tyrosine kinase c-Kit in A-V fistula neointima formation. Initially, c-Kit was found in the neointima and adventitia of human brachiobasilic fistulae, whereas it was barely detectable in control veins harvested at the time of access creation. Using the rat A-V fistula model to study venous vascular remodeling, we analyzed the spatial and temporal pattern of c-Kit expression in the fistula wall. Interestingly, c-Kit immunoreactivity increased with time after anastomosis, which concurred with the accumulation of cells in the venous intima. In addition, c-Kit expression in A-V fistulae was positively altered by chronic kidney failure conditions. Both blockade of c-Kit with imatinib mesylate (Gleevec) and inhibition of stem cell factor production with a specific short hairpin RNA prevented NIH in the outflow vein of experimental fistulae. In agreement with these data, impaired c-Kit activity compromised the development of NIH in A-V fistulae created in c-KitW/Wv mutant mice. These results suggest that targeting of the c-Kit signaling pathway may be an effective approach to prevent postoperative NIH in A-V fistulae. PMID:25186298

  13. Conformal boundaries of warped products

    DEFF Research Database (Denmark)

    Kokkendorff, Simon Lyngby

    2006-01-01

    In this note we prove a result on how to determine the conformal boundary of a type of warped product of two length spaces in terms of the individual conformal boundaries. In the situation, that we treat, the warping and conformal distortion functions are functions of distance to a base point....... The result is applied to produce examples of CAT(0)-spaces, where the conformal and ideal boundaries differ in interesting ways....

  14. A method for detecting nonlinear determinism in normal and epileptic brain EEG signals.

    Science.gov (United States)

    Meghdadi, Amir H; Fazel-Rezai, Reza; Aghakhani, Yahya

    2007-01-01

    A robust method of detecting determinism for short time series is proposed and applied to both healthy and epileptic EEG signals. The method provides a robust measure of determinism through characterizing the trajectories of the signal components which are obtained through singular value decomposition. Robustness of the method is shown by calculating proposed index of determinism at different levels of white and colored noise added to a simulated chaotic signal. The method is shown to be able to detect determinism at considerably high levels of additive noise. The method is then applied to both intracranial and scalp EEG recordings collected in different data sets for healthy and epileptic brain signals. The results show that for all of the studied EEG data sets there is enough evidence of determinism. The determinism is more significant for intracranial EEG recordings particularly during seizure activity.

  15. 40 CFR 93.154 - Conformity analysis.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Conformity analysis. 93.154 Section 93...) DETERMINING CONFORMITY OF FEDERAL ACTIONS TO STATE OR FEDERAL IMPLEMENTATION PLANS Determining Conformity of General Federal Actions to State or Federal Implementation Plans § 93.154 Conformity analysis. Any Federal...

  16. Microbiota promote secretory cell determination in the intestinal epithelium by modulating host Notch signaling.

    Science.gov (United States)

    Troll, Joshua V; Hamilton, M Kristina; Abel, Melissa L; Ganz, Julia; Bates, Jennifer M; Stephens, W Zac; Melancon, Ellie; van der Vaart, Michiel; Meijer, Annemarie H; Distel, Martin; Eisen, Judith S; Guillemin, Karen

    2018-02-23

    Resident microbes promote many aspects of host development, although the mechanisms by which microbiota influence host tissues remain unclear. We showed previously that the microbiota is required for allocation of appropriate numbers of secretory cells in the zebrafish intestinal epithelium. Because Notch signaling is crucial for secretory fate determination, we conducted epistasis experiments to establish whether the microbiota modulates host Notch signaling. We also investigated whether innate immune signaling transduces microbiota cues via the Myd88 adaptor protein. We provide the first evidence that microbiota-induced, Myd88-dependent signaling inhibits host Notch signaling in the intestinal epithelium, thereby promoting secretory cell fate determination. These results connect microbiota activity via innate immune signaling to the Notch pathway, which also plays crucial roles in intestinal homeostasis throughout life and when impaired can result in chronic inflammation and cancer. © 2018. Published by The Company of Biologists Ltd.

  17. A two-step recognition of signal sequences determines the translocation efficiency of proteins.

    OpenAIRE

    Belin, D; Bost, S; Vassalli, J D; Strub, K

    1996-01-01

    The cytosolic and secreted, N-glycosylated, forms of plasminogen activator inhibitor-2 (PAI-2) are generated by facultative translocation. To study the molecular events that result in the bi-topological distribution of proteins, we determined in vitro the capacities of several signal sequences to bind the signal recognition particle (SRP) during targeting, and to promote vectorial transport of murine PAI-2 (mPAI-2). Interestingly, the six signal sequences we compared (mPAI-2 and three mutated...

  18. Stationary analysis of signals and ratio decay determination in BWR type reactors by neuronal network

    International Nuclear Information System (INIS)

    Sanchis, R.; Palomo, M. J.; Munoz-Cobo, J. L.

    1998-01-01

    The signals registered in the nuclear plants have non stationary characteristics, in numerous times. This made difficult the application of the methods of analysis. There are determinate temporal intervals in that the signal is stationary with determinate mean, value together of zones with corrupt registers, and other zones with mean value distinct, but stationary during a temporal interval. The methodology consist in a stationary analysis to the signal received of the nuclear plant. With the Gabor Transformation are determined the temporal intervals of the stationary signals, synthesised it, as previous phase to the application of the methods of the analysis of stability parameters with methods ARMA, SVD, Neural Net,... to the reconstructed signal. 4 refs. (Author)

  19. Conformal Infinity

    Directory of Open Access Journals (Sweden)

    Frauendiener Jörg

    2000-08-01

    Full Text Available The notion of conformal infinity has a long history within the research in Einstein's theory of gravity. Today, ``conformal infinity'' is related with almost all other branches of research in general relativity, from quantisation procedures to abstract mathematical issues to numerical applications. This review article attempts to show how this concept gradually and inevitably evolved out of physical issues, namely the need to understand gravitational radiation and isolated systems within the theory of gravitation and how it lends itself very naturally to solve radiation problems in numerical relativity. The fundamental concept of null-infinity is introduced. Friedrich's regular conformal field equations are presented and various initial value problems for them are discussed. Finally, it is shown that the conformal field equations provide a very powerful method within numerical relativity to study global problems such as gravitational wave propagation and detection.

  20. Conformal Infinity.

    Science.gov (United States)

    Frauendiener, Jörg

    2004-01-01

    The notion of conformal infinity has a long history within the research in Einstein's theory of gravity. Today, "conformal infinity" is related to almost all other branches of research in general relativity, from quantisation procedures to abstract mathematical issues to numerical applications. This review article attempts to show how this concept gradually and inevitably evolved from physical issues, namely the need to understand gravitational radiation and isolated systems within the theory of gravitation, and how it lends itself very naturally to the solution of radiation problems in numerical relativity. The fundamental concept of null-infinity is introduced. Friedrich's regular conformal field equations are presented and various initial value problems for them are discussed. Finally, it is shown that the conformal field equations provide a very powerful method within numerical relativity to study global problems such as gravitational wave propagation and detection.

  1. Conformal Infinity

    Directory of Open Access Journals (Sweden)

    Frauendiener Jörg

    2004-01-01

    Full Text Available The notion of conformal infinity has a long history within the research in Einstein's theory of gravity. Today, 'conformal infinity' is related to almost all other branches of research in general relativity, from quantisation procedures to abstract mathematical issues to numerical applications. This review article attempts to show how this concept gradually and inevitably evolved from physical issues, namely the need to understand gravitational radiation and isolated systems within the theory of gravitation, and how it lends itself very naturally to the solution of radiation problems in numerical relativity. The fundamental concept of null-infinity is introduced. Friedrich's regular conformal field equations are presented and various initial value problems for them are discussed. Finally, it is shown that the conformal field equations provide a very powerful method within numerical relativity to study global problems such as gravitational wave propagation and detection.

  2. General Conformity

    Science.gov (United States)

    The General Conformity requirements ensure that the actions taken by federal agencies in nonattainment and maintenance areas do not interfere with a state’s plans to meet national standards for air quality.

  3. Conformal Infinity

    OpenAIRE

    Frauendiener, J?rg

    2000-01-01

    The notion of conformal infinity has a long history within the research in Einstein's theory of gravity. Today, 'conformal infinity' is related to almost all other branches of research in general relativity, from quantisation procedures to abstract mathematical issues to numerical applications. This review article attempts to show how this concept gradually and inevitably evolved from physical issues, namely the need to understand gravitational radiation and isolated systems within the theory...

  4. The probability distribution of side-chain conformations in [Leu] and [Met]enkephalin determines the potency and selectivity to mu and delta opiate receptors

    DEFF Research Database (Denmark)

    Nielsen, Bjørn Gilbert; Jensen, Morten Østergaard; Bohr, Henrik

    2003-01-01

    The structure of enkephalin, a small neuropeptide with five amino acids, has been simulated on computers using molecular dynamics. Such simulations exhibit a few stable conformations, which also have been identified experimentally. The simulations provide the possibility to perform cluster analysis...... in the space defined by potentially pharmacophoric measures such as dihedral angles, side-chain orientation, etc. By analyzing the statistics of the resulting clusters, the probability distribution of the side-chain conformations may be determined. These probabilities allow us to predict the selectivity...... of [Leu]enkephalin and [Met]enkephalin to the known mu- and delta-type opiate receptors to which they bind as agonists. Other plausible consequences of these probability distributions are discussed in relation to the way in which they may influence the dynamics of the synapse....

  5. Use of the neutron diffraction - H/D exchange technique to determine the conformational dynamics of trypsin

    International Nuclear Information System (INIS)

    Kossiakoff, A.A.

    1982-01-01

    Reported here are studies analyzing the extent and nature of the inherent conformational fluctuations in trypsin by neutron diffraction - hydrogen exchange techniques. The pattern of exchange investigates systematic relationships between exchangeable sites and the structural and chemical properties of the molecule. Our findings that pH 7, 20 0 and 1 year of soaking all sites of trypsin are fully exchanged except those which are especially well protected by the structure. Essentially all the sites in which the peptide hydrogens are bonded directly to water molecules - either in the bulk solvent regions or in interior clusters - are fully exchanged. 41 references, 10 figures

  6. Conformation radiotherapy and conformal radiotherapy

    International Nuclear Information System (INIS)

    Morita, Kozo

    1999-01-01

    In order to coincide the high dose region to the target volume, the 'Conformation Radiotherapy Technique' using the multileaf collimator and the device for 'hollow-out technique' was developed by Prof. S. Takahashi in 1960. This technique can be classified a type of 2D-dynamic conformal RT techniques. By the clinical application of this technique, the late complications of the lens, the intestine and the urinary bladder after radiotherapy for the maxillary cancer and the cervical cancer decreased. Since 1980's the exact position and shape of the tumor and the surrounding normal tissues can be easily obtained by the tremendous development of the CT/MRI imaging technique. As a result, various kinds of new conformal techniques such as the 3D-CRT, the dose intensity modulation, the tomotherapy have been developed since the beginning of 1990'. Several 'dose escalation study with 2D-/3D conformal RT' is now under way to improve the treatment results. (author)

  7. Determining the Effect of Catechins on SOD1 Conformation and Aggregation by Ion Mobility Mass Spectrometry Combined with Optical Spectroscopy

    Science.gov (United States)

    Zhao, Bing; Zhuang, Xiaoyu; Pi, Zifeng; Liu, Shu; Liu, Zhiqiang; Song, Fengrui

    2018-02-01

    The aggregation of Cu,Zn-superoxide dismutase (SOD1) plays an important role in the etiology of amyotrophic lateral sclerosis (ALS). For the disruption of ALS progression, discovering new drugs or compounds that can prevent SOD1 aggregation is important. In this study, ESI-MS was used to investigate the interaction of catechins and SOD1. The noncovalent complex of catechins that interact with SOD1 was found and retained in the gas phase under native ESI-MS condition. The conformation changes of SOD1 after binding with catechins were also explored via traveling wave ion mobility (IM) spectrometry. Epigallocatechin gallate (EGCG) can stabilize SOD1 conformation against unfolding in three catechins. To further evaluate the efficacy of EGCG, we monitored the fluorescence changes of dimer E2,E2,-SOD1(apo-SOD1, E:empty) with and without ligands under denaturation conditions, and found that EGCG can inhibit apo-SOD1 aggregation. In addition, the circular dichroism spectra of the samples showed that EGCG can decrease the β-sheet content of SOD1, which can produce aggregates. These results indicated that orthogonal separation dimension in the gas-phase IM coupled with ESI-MS (ESI-IM-MS) can potentially provide insight into the interaction between SOD1 and small molecules. The advantage is that it dramatically decreases the analysis time. Meantime, optical spectroscopy techniques can be used to confirm ESI-IM-MS results. [Figure not available: see fulltext.

  8. Conformal Gravity

    International Nuclear Information System (INIS)

    Hooft, G.

    2012-01-01

    The dynamical degree of freedom for the gravitational force is the metric tensor, having 10 locally independent degrees of freedom (of which 4 can be used to fix the coordinate choice). In conformal gravity, we split this field into an overall scalar factor and a nine-component remainder. All unrenormalizable infinities are in this remainder, while the scalar component can be handled like any other scalar field such as the Higgs field. In this formalism, conformal symmetry is spontaneously broken. An imperative demand on any healthy quantum gravity theory is that black holes should be described as quantum systems with micro-states as dictated by the Hawking-Bekenstein theory. This requires conformal symmetry that may be broken spontaneously but not explicitly, and this means that all conformal anomalies must cancel out. Cancellation of conformal anomalies yields constraints on the matter sector as described by some universal field theory. Thus black hole physics may eventually be of help in the construction of unified field theories. (author)

  9. Fermion-scalar conformal blocks

    Energy Technology Data Exchange (ETDEWEB)

    Iliesiu, Luca [Joseph Henry Laboratories, Princeton University,Washington Road, Princeton, NJ 08544 (United States); Kos, Filip [Department of Physics, Yale University,217 Prospect Street, New Haven, CT 06520 (United States); Poland, David [Department of Physics, Yale University,217 Prospect Street, New Haven, CT 06520 (United States); School of Natural Sciences, Institute for Advanced Study,1 Einstein Dr, Princeton, New Jersey 08540 (United States); Pufu, Silviu S. [Joseph Henry Laboratories, Princeton University,Washington Road, Princeton, NJ 08544 (United States); Simmons-Duffin, David [School of Natural Sciences, Institute for Advanced Study,1 Einstein Dr, Princeton, New Jersey 08540 (United States); Yacoby, Ran [Joseph Henry Laboratories, Princeton University,Washington Road, Princeton, NJ 08544 (United States)

    2016-04-13

    We compute the conformal blocks associated with scalar-scalar-fermion-fermion 4-point functions in 3D CFTs. Together with the known scalar conformal blocks, our result completes the task of determining the so-called ‘seed blocks’ in three dimensions. Conformal blocks associated with 4-point functions of operators with arbitrary spins can now be determined from these seed blocks by using known differential operators.

  10. Accurate determination of interfacial protein secondary structure by combining interfacial-sensitive amide I and amide III spectral signals.

    Science.gov (United States)

    Ye, Shuji; Li, Hongchun; Yang, Weilai; Luo, Yi

    2014-01-29

    Accurate determination of protein structures at the interface is essential to understand the nature of interfacial protein interactions, but it can only be done with a few, very limited experimental methods. Here, we demonstrate for the first time that sum frequency generation vibrational spectroscopy can unambiguously differentiate the interfacial protein secondary structures by combining surface-sensitive amide I and amide III spectral signals. This combination offers a powerful tool to directly distinguish random-coil (disordered) and α-helical structures in proteins. From a systematic study on the interactions between several antimicrobial peptides (including LKα14, mastoparan X, cecropin P1, melittin, and pardaxin) and lipid bilayers, it is found that the spectral profiles of the random-coil and α-helical structures are well separated in the amide III spectra, appearing below and above 1260 cm(-1), respectively. For the peptides with a straight backbone chain, the strength ratio for the peaks of the random-coil and α-helical structures shows a distinct linear relationship with the fraction of the disordered structure deduced from independent NMR experiments reported in the literature. It is revealed that increasing the fraction of negatively charged lipids can induce a conformational change of pardaxin from random-coil to α-helical structures. This experimental protocol can be employed for determining the interfacial protein secondary structures and dynamics in situ and in real time without extraneous labels.

  11. The conformation of 23S rRNA nucleotide A2058 determines its recognition by the ErmE methyltransferase

    DEFF Research Database (Denmark)

    Vester, B; Hansen, L H; Douthwaite, S

    1995-01-01

    the effects of mutations around position A2058 on methylation. Mutagenizing A2058 (to G or U) completely abolishes methylation of 23S rRNA by ErmE. No methylation occurred at other sites in the rRNA, demonstrating the fidelity of ErmE for A2058. Breaking the neighboring G2057-C2611 Watson-Crick base pair...... by introducing either an A2057 or a U2611 mutation, greatly reduces the rate of methylation at A2058. Methylation remains impaired after these mutations have been combined to create a new A2057-U2611 Watson-Crick base interaction. The conformation of this region in 23S rRNA was probed with chemical reagents...

  12. Nanomechanics of the substrate binding domain of Hsp70 determine its allosteric ATP-induced conformational change.

    Science.gov (United States)

    Mandal, Soumit Sankar; Merz, Dale R; Buchsteiner, Maximilian; Dima, Ruxandra I; Rief, Matthias; Žoldák, Gabriel

    2017-06-06

    Owing to the cooperativity of protein structures, it is often almost impossible to identify independent subunits, flexible regions, or hinges simply by visual inspection of static snapshots. Here, we use single-molecule force experiments and simulations to apply tension across the substrate binding domain (SBD) of heat shock protein 70 (Hsp70) to pinpoint mechanical units and flexible hinges. The SBD consists of two nanomechanical units matching 3D structural parts, called the α- and β-subdomain. We identified a flexible region within the rigid β-subdomain that gives way under load, thus opening up the α/β interface. In exactly this region, structural changes occur in the ATP-induced opening of Hsp70 to allow substrate exchange. Our results show that the SBD's ability to undergo large conformational changes is already encoded by passive mechanics of the individual elements.

  13. Grazing incidence X-ray diffraction study of the tilted phases of Langmuir films: Determination of molecular conformations using simulated annealing

    International Nuclear Information System (INIS)

    Pignat, J.; Daillant, J.; Cantin, S.; Perrot, F.; Konovalov, O.

    2007-01-01

    We have analyzed grazing incidence X-ray diffraction (GIXD) data from condensed phases of Langmuir films of long-chain fatty acids at the air-water using a new method consisting in a careful extraction of the structure factors followed by fitting of molecular parameters using simulated annealing. We show that the information contained in GIXD spectra is enough to obtain near-atomic structural information. In particular, we directly determine the orientation of the chain backbone planes and of the carboxylic headgroups, and we evaluate chain conformation defects

  14. Grazing incidence X-ray diffraction study of the tilted phases of Langmuir films: Determination of molecular conformations using simulated annealing

    Energy Technology Data Exchange (ETDEWEB)

    Pignat, J. [LIONS/Service de Chimie Moleculaire, CEA-Saclay bat. 125, F-91191 Gif-sur-Yvette Cedex (France); LPPI, universite de Cergy-Pontoise, 5 mail Gay-Lussac Neuville/Oise, 95031 Cergy-Pontoise Cedex (France); Daillant, J. [LIONS/Service de Chimie Moleculaire, CEA-Saclay bat. 125, F-91191 Gif-sur-Yvette Cedex (France)]. E-mail: jean.daillant@cea.fr; Cantin, S. [LPPI, universite de Cergy-Pontoise, 5 mail Gay-Lussac Neuville/Oise, 95031 Cergy-Pontoise Cedex (France); Perrot, F. [LPPI, universite de Cergy-Pontoise, 5 mail Gay-Lussac Neuville/Oise, 95031 Cergy-Pontoise Cedex (France); Konovalov, O. [ESRF, 6 rue Jules Horowitz, BP220, 38043 Grenoble Cedex (France)

    2007-05-23

    We have analyzed grazing incidence X-ray diffraction (GIXD) data from condensed phases of Langmuir films of long-chain fatty acids at the air-water using a new method consisting in a careful extraction of the structure factors followed by fitting of molecular parameters using simulated annealing. We show that the information contained in GIXD spectra is enough to obtain near-atomic structural information. In particular, we directly determine the orientation of the chain backbone planes and of the carboxylic headgroups, and we evaluate chain conformation defects.

  15. In silico Exploration of the Conformational Universe of GPCRs.

    Science.gov (United States)

    Rodríguez-Espigares, Ismael; Kaczor, Agnieszka A; Selent, Jana

    2016-07-01

    The structural plasticity of G protein coupled receptors (GPCRs) leads to a conformational universe going from inactive to active receptor states with several intermediate states. Many of them have not been captured yet and their role for GPCR activation is not well understood. The study of this conformational space and the transition dynamics between different receptor populations is a major challenge in molecular biophysics. The rational design of effector molecules that target such receptor populations allows fine-tuning receptor signalling with higher specificity to produce drugs with safer therapeutic profiles. In this minireview, we outline highly conserved receptor regions which are considered determinant for the establishment of distinct receptor states. We then discuss in-silico approaches such as dimensionality reduction methods and Markov State Models to explore the GPCR conformational universe and exploit the obtained conformations through structure-based drug design. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Chain Assembly and Disassembly Processes Differently Affect the Conformational Space of Ubiquitin Chains.

    Science.gov (United States)

    Kniss, Andreas; Schuetz, Denise; Kazemi, Sina; Pluska, Lukas; Spindler, Philipp E; Rogov, Vladimir V; Husnjak, Koraljka; Dikic, Ivan; Güntert, Peter; Sommer, Thomas; Prisner, Thomas F; Dötsch, Volker

    2018-02-06

    Ubiquitination is the most versatile posttranslational modification. The information is encoded by linkage type as well as chain length, which are translated by ubiquitin binding domains into specific signaling events. Chain topology determines the conformational space of a ubiquitin chain and adds an additional regulatory layer to this ubiquitin code. In particular, processes that modify chain length will be affected by chain conformations as they require access to the elongation or cleavage sites. We investigated conformational distributions in the context of chain elongation and disassembly using pulsed electron-electron double resonance spectroscopy in combination with molecular modeling. Analysis of the conformational space of diubiquitin revealed conformational selection or remodeling as mechanisms for chain recognition during elongation or hydrolysis, respectively. Chain elongation to tetraubiquitin increases the sampled conformational space, suggesting that a high intrinsic flexibility of K48-linked chains may contribute to efficient proteasomal degradation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Determination of molecular structure of succinic acid in a very complex conformational landscape: Gas-phase electron diffraction (GED) and ab initio studies

    Science.gov (United States)

    Vogt, Natalja; Abaev, Maxim A.; Rykov, Anatolii N.; Shishkov, Igor F.

    2011-06-01

    The molecular structure of succinic acid has been investigated by the gas-phase electron diffraction (GED) method for the first time. According to predictions of MP2/cc-pVTZ calculations, the molecule has 18 stable conformers with the C sbnd C sbnd C sbnd C chain in the gauche ( G) or anti ( A) configuration, and four of them, I ( G), II ( A), III ( G) and IV ( A) belonging to the C 2, C 2h, C 1 and C 1 point groups, respectively, with relative energies ΔE ZPE within 2.2 kcal/mol can be present at the experimental temperature of 445 K in noticeable amounts. The ratio of the conformers I:II:III:IV = 45(15):20(15):10(assumed):25(15) (in %) has been determined in the GED analysis guided by theoretical predictions. To take into account vibrational effects, the corrections Δ( r e - r a) to the experimental r a bond lengths were calculated from the MP2/cc-pVTZ quadratic and cubic force constants. The obtained equilibrium structural parameters of the dominant conformer I are the following (bond lengths in Å, angles in degrees): r e(C sp3sbnd C sp3) = 1.508(3), r e(C sp3sbnd C sp2) = 1.499(2), r e(C sbnd O) = 1.343(2), r e(C dbnd O) = 1.202(1), e(C sbnd C sbnd C) = 111.8(4), e(C sbnd C sbnd O) = 112.0(4), e(O sbnd C dbnd O) = 123.0(1), τ(C sbnd C sbnd C sbnd C) = 69.9(11). Yielding the best agreement with the GED structure, the MP2/cc-pVQZ approximation overestimates the C sbnd O and C dbnd O bond lengths by ca. 0.005(2) Å.

  18. Conformality lost

    International Nuclear Information System (INIS)

    Kaplan, David B.; Lee, Jong-Wan; Son, Dam T.; Stephanov, Mikhail A.

    2009-01-01

    We consider zero-temperature transitions from conformal to nonconformal phases in quantum theories. We argue that there are three generic mechanisms for the loss of conformality in any number of dimensions: (i) fixed point goes to zero coupling, (ii) fixed point runs off to infinite coupling, or (iii) an IR fixed point annihilates with a UV fixed point and they both disappear into the complex plane. We give both relativistic and nonrelativistic examples of the last case in various dimensions and show that the critical behavior of the mass gap behaves similarly to the correlation length in the finite temperature Berezinskii-Kosterlitz-Thouless (BKT) phase transition in two dimensions, ξ∼exp(c/|T-T c | 1/2 ). We speculate that the chiral phase transition in QCD at large number of fermion flavors belongs to this universality class, and attempt to identify the UV fixed point that annihilates with the Banks-Zaks fixed point at the lower end of the conformal window.

  19. Treatment Planning Study to Determine Potential Benefit of Intensity-Modulated Radiotherapy Versus Conformal Radiotherapy for Unresectable Hepatic Malignancies

    International Nuclear Information System (INIS)

    Eccles, Cynthia L.; Bissonnette, Jean-Pierre; Craig, Tim; Taremi, Mojgan; Wu Xia; Dawson, Laura A.

    2008-01-01

    Purpose: To compare intensity-modulated radiotherapy (IMRT) with conformal RT (CRT) for hypofractionated isotoxicity liver RT and explore dose escalation using IMRT for the same/improved nominal risk of liver toxicity in a treatment planning study. Methods and Materials: A total of 26 CRT plans were evaluated. Prescription doses (24-54 Gy within six fractions) were individualized on the basis of the effective liver volume irradiated maintaining ≤5% risk of radiation-induced liver disease. The dose constraints included bowel (0.5 cm 3 ) and stomach (0.5 cm 3 ) to ≤30 Gy, spinal cord to ≤25 Gy, and planning target volume (PTV) to ≤140% of the prescribed dose. Two groups were evaluated: (1) PTV overlapping or directly adjacent to serial functioning normal tissues (n = 14), and (2) the liver as the dose-limiting normal tissue (n = 12). IMRT plans using direct machine parameter optimization maintained the CRT plan beam arrangements, an estimated radiation-induced liver disease risk of 5%, and underwent dose escalation, if all normal tissue constraints were maintained. Results: IMRT improved PTV coverage in 19 of 26 plans (73%). Dose escalation was feasible in 9 cases by an average of 3.8 Gy (range, 0.6-13.2) in six fractions. Three of seven plans without improved PTV coverage had small gross tumor volumes (≤105 cm 3 ) already receiving 54 Gy, the maximal prescription dose allowed. In the remaining cases, the PTV range was 9.6-689 cm 3 ; two had overlapped organs at risk; and one had four targets. IMRT did not improve these plans owing to poor target coverage (n = 2) and nonliver (n = 2) dose limits. Conclusion: Direct machine parameter optimization IMRT improved PTV coverage while maintaining normal tissue tolerances in most CRT liver plans. Dose escalation was possible in a minority of patients

  20. Fgf9 and Wnt4 act as antagonistic signals to regulate mammalian sex determination.

    Directory of Open Access Journals (Sweden)

    Yuna Kim

    2006-06-01

    Full Text Available The genes encoding members of the wingless-related MMTV integration site (WNT and fibroblast growth factor (FGF families coordinate growth, morphogenesis, and differentiation in many fields of cells during development. In the mouse, Fgf9 and Wnt4 are expressed in gonads of both sexes prior to sex determination. Loss of Fgf9 leads to XY sex reversal, whereas loss of Wnt4 results in partial testis development in XX gonads. However, the relationship between these signals and the male sex-determining gene, Sry, was unknown. We show through gain- and loss-of-function experiments that fibroblast growth factor 9 (FGF9 and WNT4 act as opposing signals to regulate sex determination. In the mouse XY gonad, Sry normally initiates a feed-forward loop between Sox9 and Fgf9, which up-regulates Fgf9 and represses Wnt4 to establish the testis pathway. Surprisingly, loss of Wnt4 in XX gonads is sufficient to up-regulate Fgf9 and Sox9 in the absence of Sry. These data suggest that the fate of the gonad is controlled by antagonism between Fgf9 and Wnt4. The role of the male sex-determining switch--Sry in the case of mammals--is to tip the balance between these underlying patterning signals. In principle, sex determination in other vertebrates may operate through any switch that introduces an imbalance between these two signaling pathways.

  1. A New Wavelet Threshold Determination Method Considering Interscale Correlation in Signal Denoising

    Directory of Open Access Journals (Sweden)

    Can He

    2015-01-01

    Full Text Available Due to simple calculation and good denoising effect, wavelet threshold denoising method has been widely used in signal denoising. In this method, the threshold is an important parameter that affects the denoising effect. In order to improve the denoising effect of the existing methods, a new threshold considering interscale correlation is presented. Firstly, a new correlation index is proposed based on the propagation characteristics of the wavelet coefficients. Then, a threshold determination strategy is obtained using the new index. At the end of the paper, a simulation experiment is given to verify the effectiveness of the proposed method. In the experiment, four benchmark signals are used as test signals. Simulation results show that the proposed method can achieve a good denoising effect under various signal types, noise intensities, and thresholding functions.

  2. Determination of the X, Y coordinates of a pulsed ultrasonic source of signals

    International Nuclear Information System (INIS)

    Sokolov, B.V.; Shemyakin, V.V.

    1975-01-01

    A range of problems in predicting the emergency state of large-scale vessel housings are determined for subsequent solution involving acoustic emission phenomena. The authors specify the position of a given problem and present substantial grounds for selecting the minimum number of group signal receivers for unambiguous calculation of the location of the source. Relationships are obtained between X, Y - the coordinates of the pulse signal source - and experimentally measured time differences in recording of signals by group receivers. A criterion is given for selecting the true signal group combination when the receivers simultaneously record waves from several sources. Specific suggestions are made regarding the experimental information to be stored in a central computer for subsequent processing [ru

  3. Analysis Sparse Representation for Nonnegative Signals Based on Determinant Measure by DC Programming

    Directory of Open Access Journals (Sweden)

    Yujie Li

    2018-01-01

    Full Text Available Analysis sparse representation has recently emerged as an alternative approach to the synthesis sparse model. Most existing algorithms typically employ the l0-norm, which is generally NP-hard. Other existing algorithms employ the l1-norm to relax the l0-norm, which sometimes cannot promote adequate sparsity. Most of these existing algorithms focus on general signals and are not suitable for nonnegative signals. However, many signals are necessarily nonnegative such as spectral data. In this paper, we present a novel and efficient analysis dictionary learning algorithm for nonnegative signals with the determinant-type sparsity measure which is convex and differentiable. The analysis sparse representation can be cast in three subproblems, sparse coding, dictionary update, and signal update, because the determinant-type sparsity measure would result in a complex nonconvex optimization problem, which cannot be easily solved by standard convex optimization methods. Therefore, in the proposed algorithms, we use a difference of convex (DC programming scheme for solving the nonconvex problem. According to our theoretical analysis and simulation study, the main advantage of the proposed algorithm is its greater dictionary learning efficiency, particularly compared with state-of-the-art algorithms. In addition, our proposed algorithm performs well in image denoising.

  4. Halo-independent determination of the unmodulated WIMP signal in DAMA: the isotropic case

    Energy Technology Data Exchange (ETDEWEB)

    Gondolo, Paolo [Department of Physics, University of Utah, 115 South 1400 East #201, Salt Lake City, Utah 84112-0830 (United States); Scopel, Stefano, E-mail: paolo.gondolo@utah.edu, E-mail: scopel@sogang.ac.kr [Department of Physics, Sogang University, Seoul 121-742 (Korea, Republic of)

    2017-09-01

    We present a halo-independent determination of the unmodulated signal corresponding to the DAMA modulation if interpreted as due to dark matter weakly interacting massive particles (WIMPs). First we show how a modulated signal gives information on the WIMP velocity distribution function in the Galactic rest frame from which the unmodulated signal descends. Then we describe a mathematically-sound profile likelihood analysis in which the likelihood is profiled over a continuum of nuisance parameters (namely, the WIMP velocity distribution). As a first application of the method, which is very general and valid for any class of velocity distributions, we restrict the analysis to velocity distributions that are isotropic in the Galactic frame. In this way we obtain halo-independent maximum-likelihood estimates and confidence intervals for the DAMA unmodulated signal. We find that the estimated unmodulated signal is in line with expectations for a WIMP-induced modulation and is compatible with the DAMA background+signal rate. Specifically, for the isotropic case we find that the modulated amplitude ranges between a few percent and about 25% of the unmodulated amplitude, depending on the WIMP mass.

  5. A two-step recognition of signal sequences determines the translocation efficiency of proteins.

    Science.gov (United States)

    Belin, D; Bost, S; Vassalli, J D; Strub, K

    1996-02-01

    The cytosolic and secreted, N-glycosylated, forms of plasminogen activator inhibitor-2 (PAI-2) are generated by facultative translocation. To study the molecular events that result in the bi-topological distribution of proteins, we determined in vitro the capacities of several signal sequences to bind the signal recognition particle (SRP) during targeting, and to promote vectorial transport of murine PAI-2 (mPAI-2). Interestingly, the six signal sequences we compared (mPAI-2 and three mutated derivatives thereof, ovalbumin and preprolactin) were found to have the differential activities in the two events. For example, the mPAI-2 signal sequence first binds SRP with moderate efficiency and secondly promotes the vectorial transport of only a fraction of the SRP-bound nascent chains. Our results provide evidence that the translocation efficiency of proteins can be controlled by the recognition of their signal sequences at two steps: during SRP-mediated targeting and during formation of a committed translocation complex. This second recognition may occur at several time points during the insertion/translocation step. In conclusion, signal sequences have a more complex structure than previously anticipated, allowing for multiple and independent interactions with the translocation machinery.

  6. Nanohertz frequency determination for the gravity probe B high frequency superconducting quantum interference device signal.

    Science.gov (United States)

    Salomon, M; Conklin, J W; Kozaczuk, J; Berberian, J E; Keiser, G M; Silbergleit, A S; Worden, P; Santiago, D I

    2011-12-01

    In this paper, we present a method to measure the frequency and the frequency change rate of a digital signal. This method consists of three consecutive algorithms: frequency interpolation, phase differencing, and a third algorithm specifically designed and tested by the authors. The succession of these three algorithms allowed a 5 parts in 10(10) resolution in frequency determination. The algorithm developed by the authors can be applied to a sampled scalar signal such that a model linking the harmonics of its main frequency to the underlying physical phenomenon is available. This method was developed in the framework of the gravity probe B (GP-B) mission. It was applied to the high frequency (HF) component of GP-B's superconducting quantum interference device signal, whose main frequency f(z) is close to the spin frequency of the gyroscopes used in the experiment. A 30 nHz resolution in signal frequency and a 0.1 pHz/s resolution in its decay rate were achieved out of a succession of 1.86 s-long stretches of signal sampled at 2200 Hz. This paper describes the underlying theory of the frequency measurement method as well as its application to GP-B's HF science signal.

  7. Synthesis, three-dimensional structure, conformation and correct chemical shift assignment determination of pharmaceutical molecules by NMR and molecular modeling

    Energy Technology Data Exchange (ETDEWEB)

    Azeredo, Sirlene O.F. de; Sales, Edijane M.; Figueroa-Villar, José D., E-mail: jdfv2009@gmail.com [Instituto Militar de Engenharia (IME), Rio de Janeiro, RJ (Brazil). Grupo de Ressonância Magnética Nuclear e Química Medicinal

    2017-07-01

    This work includes the synthesis of phenanthrenequinone guanylhydrazone and phenanthro[9,10-e][1,2,4]triazin-3-amine to be tested as intercalate with DNA for treatment of cancer. The other synthesized product, 2-[(4-chlorophenylamino)methylene]malononitrile, was designed for future determination of its activity against leishmaniasis. A common problem about some articles on the literature is that some previously published compounds display error of their molecular structures. In this article it is shown the application of several procedures of nuclear magnetic resonance (NMR) to determine the complete molecular structure and the non questionable chemical shift assignment of the synthesized compounds, and also their analysis by molecular modeling to confirm the NMR results. To determine the capacity of pharmacological compounds to interact with biological targets is determined by docking. This work is to motivate the application of NMR and molecular modeling on organic synthesis, being a process that is very important for the study of the prepared compounds as interactions with biological targets by NMR. (author)

  8. Synthesis, three-dimensional structure, conformation and correct chemical shift assignment determination of pharmaceutical molecules by NMR and molecular modeling

    International Nuclear Information System (INIS)

    Azeredo, Sirlene O.F. de; Sales, Edijane M.; Figueroa-Villar, José D.

    2017-01-01

    This work includes the synthesis of phenanthrenequinone guanylhydrazone and phenanthro[9,10-e][1,2,4]triazin-3-amine to be tested as intercalate with DNA for treatment of cancer. The other synthesized product, 2-[(4-chlorophenylamino)methylene]malononitrile, was designed for future determination of its activity against leishmaniasis. A common problem about some articles on the literature is that some previously published compounds display error of their molecular structures. In this article it is shown the application of several procedures of nuclear magnetic resonance (NMR) to determine the complete molecular structure and the non questionable chemical shift assignment of the synthesized compounds, and also their analysis by molecular modeling to confirm the NMR results. To determine the capacity of pharmacological compounds to interact with biological targets is determined by docking. This work is to motivate the application of NMR and molecular modeling on organic synthesis, being a process that is very important for the study of the prepared compounds as interactions with biological targets by NMR. (author)

  9. Cell fate in the Arabidopsis root meristem determined by directional signalling.

    Science.gov (United States)

    van den Berg, C; Willemsen, V; Hage, W; Weisbeek, P; Scheres, B

    1995-11-02

    Postembryonic development in plants is achieved by apical meristems. Surgical studies and clonal analysis have revealed indirectly that cells in shoot meristems have no predictable destiny and that position is likely to play a role in the acquisition of cell identity. In contrast to animal systems, there has been no direct evidence for inductive signalling in plants until now. Here we present evidence for such signalling using laser ablation of cells in the root meristem of Arabidopsis thaliana. Although these cells show rigid clonal relationships, we now demonstrate that it is positional control that is most important in the determination of cell fate. Positional signals can be perpetuated from more mature to initial cells to guide the pattern of meristem cell differentiation. This offers an alternative to the general opinion that meristems are the source of patterning information.

  10. NRC Bulletin No. 87-02, Supplement 1: Fastener testing to determine conformance with applicable material specifications

    International Nuclear Information System (INIS)

    Rossi, C.E.

    1992-01-01

    Item 5 of NRC Compliance Bulletin 87-02 requested that all holders of operating licenses or construction permits for nuclear power reactors information regarding the identity of the suppliers and manufacturers of the safety-related and non-safety-related fasteners selected for testing. After further consideration, the NRC has determined that it needs information regarding the identity of all vendors from which safety-related and non-safety-related fasteners have been obtained within the past 10 years, a reasonable period which will not put undue burden on addressees. This information will assist the NRC in determining whether nuclear facility fasteners in use have been supplied in accordance with their intended use. In addition, this information is needed so that the NRC can properly coordinate information with other government agencies concerned with problems identified in the quality of fasteners

  11. Role of Notch signaling in cell-fate determination of human mammary stem/progenitor cells

    International Nuclear Information System (INIS)

    Dontu, Gabriela; Jackson, Kyle W; McNicholas, Erin; Kawamura, Mari J; Abdallah, Wissam M; Wicha, Max S

    2004-01-01

    Notch signaling has been implicated in the regulation of cell-fate decisions such as self-renewal of adult stem cells and differentiation of progenitor cells along a particular lineage. Moreover, depending on the cellular and developmental context, the Notch pathway acts as a regulator of cell survival and cell proliferation. Abnormal expression of Notch receptors has been found in different types of epithelial metaplastic lesions and neoplastic lesions, suggesting that Notch may act as a proto-oncogene. The vertebrate Notch1 and Notch4 homologs are involved in normal development of the mammary gland, and mutated forms of these genes are associated with development of mouse mammary tumors. In order to determine the role of Notch signaling in mammary cell-fate determination, we have utilized a newly described in vitro system in which mammary stem/progenitor cells can be cultured in suspension as nonadherent 'mammospheres'. Notch signaling was activated using exogenous ligands, or was inhibited using previously characterized Notch signaling antagonists. Utilizing this system, we demonstrate that Notch signaling can act on mammary stem cells to promote self-renewal and on early progenitor cells to promote their proliferation, as demonstrated by a 10-fold increase in secondary mammosphere formation upon addition of a Notch-activating DSL peptide. In addition to acting on stem cells, Notch signaling is also able to act on multipotent progenitor cells, facilitating myoepithelial lineage-specific commitment and proliferation. Stimulation of this pathway also promotes branching morphogenesis in three-dimensional Matrigel cultures. These effects are completely inhibited by a Notch4 blocking antibody or a gamma secretase inhibitor that blocks Notch processing. In contrast to the effects of Notch signaling on mammary stem/progenitor cells, modulation of this pathway has no discernable effect on fully committed, differentiated, mammary epithelial cells. These studies

  12. Relation between stability and resilience determines the performance of early warning signals under different environmental drivers.

    Science.gov (United States)

    Dai, Lei; Korolev, Kirill S; Gore, Jeff

    2015-08-11

    Shifting patterns of temporal fluctuations have been found to signal critical transitions in a variety of systems, from ecological communities to human physiology. However, failure of these early warning signals in some systems calls for a better understanding of their limitations. In particular, little is known about the generality of early warning signals in different deteriorating environments. In this study, we characterized how multiple environmental drivers influence the dynamics of laboratory yeast populations, which was previously shown to display alternative stable states [Dai et al., Science, 2012]. We observed that both the coefficient of variation and autocorrelation increased before population collapse in two slowly deteriorating environments, one with a rising death rate and the other one with decreasing nutrient availability. We compared the performance of early warning signals across multiple environments as "indicators for loss of resilience." We find that the varying performance is determined by how a system responds to changes in a specific driver, which can be captured by a relation between stability (recovery rate) and resilience (size of the basin of attraction). Furthermore, we demonstrate that the positive correlation between stability and resilience, as the essential assumption of indicators based on critical slowing down, can break down in this system when multiple environmental drivers are changed simultaneously. Our results suggest that the stability-resilience relation needs to be better understood for the application of early warning signals in different scenarios.

  13. Comparison of signaling interactions determining annual and perennial plant growth in response to low temperature

    Directory of Open Access Journals (Sweden)

    Astrid eWingler

    2015-01-01

    Full Text Available Low temperature inhibits plant growth despite the fact that considerable rates of photosynthetic activity can be maintained. Instead of lower rates of photosynthesis, active inhibition of cell division and expansion is primarily responsible for reduced growth. This results in sink limitation and enables plants to accumulate carbohydrates that act as compatible solutes or are stored throughout the winter to enable re-growth in spring. Regulation of growth in response to temperature therefore requires coordination with carbon metabolism, e.g. via the signaling metabolite trehalose-6-phosphate. The phytohormones gibberellins (GA and jasmonate (JA play an important role in regulating growth in response to temperature. Growth restriction at low temperature is mainly mediated by DELLA proteins, whose degradation is promoted by GA. For annual plants, it has been shown that the GA/DELLA pathway interacts with JA signaling and C-repeat binding factor (CBF dependent cold acclimation, but these interactions have not been explored in detail for perennials. Growth regulation in response to seasonal factors is, however, particularly important in perennials, especially at high latitudes. In autumn, growth cessation in trees is caused by shortening of the daylength in interaction with phytohormone signaling. In perennial grasses seasonal differences in the sensitivity to GA may enable enhanced growth in spring. This review provides an overview of the signaling interactions that determine plant growth at low temperature and highlights gaps in our knowledge, especially concerning the seasonality of signaling responses in perennial plants.

  14. Automatic Threshold Determination for a Local Approach of Change Detection in Long-Term Signal Recordings

    Directory of Open Access Journals (Sweden)

    David Hewson

    2007-01-01

    Full Text Available CUSUM (cumulative sum is a well-known method that can be used to detect changes in a signal when the parameters of this signal are known. This paper presents an adaptation of the CUSUM-based change detection algorithms to long-term signal recordings where the various hypotheses contained in the signal are unknown. The starting point of the work was the dynamic cumulative sum (DCS algorithm, previously developed for application to long-term electromyography (EMG recordings. DCS has been improved in two ways. The first was a new procedure to estimate the distribution parameters to ensure the respect of the detectability property. The second was the definition of two separate, automatically determined thresholds. One of them (lower threshold acted to stop the estimation process, the other one (upper threshold was applied to the detection function. The automatic determination of the thresholds was based on the Kullback-Leibler distance which gives information about the distance between the detected segments (events. Tests on simulated data demonstrated the efficiency of these improvements of the DCS algorithm.

  15. Determination of noise sources and space-dependent reactor transfer functions from measured output signals only

    Energy Technology Data Exchange (ETDEWEB)

    Hoogenboom, J.E.; van Dam, H.; Kleiss, E.B.J.; van Uitert, G.C.; Veldhuis, D.

    1982-01-01

    The measured cross power spectral densities of the signals from three neutron detectors and the displacement of the control rod of the 2 MW research reactor HOR at Delft have been used to determine the space-dependent reactor transfer function, the transfer function of the automatic reactor control system and the noise sources influencing the measured signals. From a block diagram of the reactor with control system and noise sources expressions were derived for the measured cross power spectral densities, which were adjusted to satisfy the requirements following from the adopted model. Then for each frequency point the required transfer functions and noise sources could be derived. The results are in agreement with those of autoregressive modelling of the reactor control feed-back loop. A method has been developed to determine the non-linear characteristics of the automatic reactor control system by analysing the non-gaussian probability density function of the power fluctuations.

  16. Determination of noise sources and space-dependent reactor transfer functions from measured output signals only

    International Nuclear Information System (INIS)

    Hoogenboom, J.E.

    1982-01-01

    The measured cross power spectral densities of the signals from three neutron detectors and the displacement of the control rod of the 2 MW research reactor HOR at Delft have been used to determine the space-dependent reactor transfer function, the transfer function of the automatic reactor control system and the noise sources influencing the measured signals. From a block diagram of the reactor with control system and noise sources expressions were derived for the measured cross power spectral densities, which were adjusted to satisfy the requirements following from the adopted model. Then for each frequency point the required transfer functions and noise sources could be derived. The results are in agreement with those of autoregressive modelling of the reactor control feed-back loop. A method has been developed to determine the non-linear characteristics of the automatic reactor control system by analysing the non-gaussian probability density function of the power fluctuations. (author)

  17. Band extension in digital methods of transfer function determinationsignal conditioners asymmetry error corrections

    Directory of Open Access Journals (Sweden)

    Zbigniew Staroszczyk

    2014-12-01

    Full Text Available [b]Abstract[/b]. In the paper, the calibrating method for error correction in transfer function determination with the use of DSP has been proposed. The correction limits/eliminates influence of transfer function input/output signal conditioners on the estimated transfer functions in the investigated object. The method exploits frequency domain conditioning paths descriptor found during training observation made on the known reference object.[b]Keywords[/b]: transfer function, band extension, error correction, phase errors

  18. Satellite single-axis attitude determination based on Automatic Dependent Surveillance - Broadcast signals

    Science.gov (United States)

    Zhou, Kaixing; Sun, Xiucong; Huang, Hai; Wang, Xinsheng; Ren, Guangwei

    2017-10-01

    The space-based Automatic Dependent Surveillance - Broadcast (ADS-B) is a new technology for air traffic management. The satellite equipped with spaceborne ADS-B system receives the broadcast signals from aircraft and transfers the message to ground stations, so as to extend the coverage area of terrestrial-based ADS-B. In this work, a novel satellite single-axis attitude determination solution based on the ADS-B receiving system is proposed. This solution utilizes the signal-to-noise ratio (SNR) measurement of the broadcast signals from aircraft to determine the boresight orientation of the ADS-B receiving antenna fixed on the satellite. The basic principle of this solution is described. The feasibility study of this new attitude determination solution is implemented, including the link budget and the access analysis. On this basis, the nonlinear least squares estimation based on the Levenberg-Marquardt method is applied to estimate the single-axis orientation. A full digital simulation has been carried out to verify the effectiveness and performance of this solution. Finally, the corresponding results are processed and presented minutely.

  19. 40 CFR 51.854 - Conformity analysis.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 2 2010-07-01 2010-07-01 false Conformity analysis. 51.854 Section 51... FOR PREPARATION, ADOPTION, AND SUBMITTAL OF IMPLEMENTATION PLANS Determining Conformity of General Federal Actions to State or Federal Implementation Plans § 51.854 Conformity analysis. Link to an...

  20. Recursion Relations for Conformal Blocks

    CERN Document Server

    Penedones, João; Yamazaki, Masahito

    2016-09-12

    In the context of conformal field theories in general space-time dimension, we find all the possible singularities of the conformal blocks as functions of the scaling dimension $\\Delta$ of the exchanged operator. In particular, we argue, using representation theory of parabolic Verma modules, that in odd spacetime dimension the singularities are only simple poles. We discuss how to use this information to write recursion relations that determine the conformal blocks. We first recover the recursion relation introduced in 1307.6856 for conformal blocks of external scalar operators. We then generalize this recursion relation for the conformal blocks associated to the four point function of three scalar and one vector operator. Finally we specialize to the case in which the vector operator is a conserved current.

  1. Determination of outdoor signal propagation via visibility analysis in outdoor wireless networks

    Directory of Open Access Journals (Sweden)

    Mustafa Coşar

    2017-02-01

    Full Text Available Wireless networks on university campuses has gained importance in recent years. These networks in major areas such as university campuses, are faced with many problems during the planning, design and establishment. These problems are among the first that comes to mind, the physical properties of the campus and is selected according to the characteristics of network equipment. There is no doubt at all points of a wireless network set up in order to provide uninterrupted service and quality of the signal is expected to be good. However, it should be understood literally cannot meet these expectations. Therefore, to solve many problems to campus planning and design can be made to have acceptable signal distribution will have the appropriate use of and satisfaction with increasing effect. In this study, due to the start of construction on the North Campus of Hitit University, wireless signal spread using the current spread has been determined with the help of geographic information systems visibility analysis. An area of 56 hectares, with the total of 9 AP the acceptable signal distribution was obtained.

  2. Use of generator substitution to determine the real attenuation of informative signals in the compromising emanation

    Directory of Open Access Journals (Sweden)

    Alexander A. Golyakhov

    2018-05-01

    Full Text Available A determination of real attenuation of information signal's radiation on a way from the source to a possible location of intelligence devices is considered to be the most difficult operation while assessing information security against leakage of electromagnetic emanation. In this context the problem of automation of this kind of measurement is of great interest. It takes considerable effort and time to measure the attenuation by existing automated systems. That is why the measurements are generally taken within the limited range of frequencies only. Along with that, a spectre of a single information impulse has a leaf-structure and is solid on every frequency leaf. So electromagnetic field intensity attenuation measurement carried on the some preselected frequencies is not able to represent the complete attenuation characteristics. The measurements of attenuation in the whole informative signal spectre within the given frequency range requires a few thousand measurements, which makes the current method ineffective and time consuming. The relevant specialized automatized measurement systems of security verification has active protection system noise measurement mode, which can be used to measure the real attenuation. In this article a rather exact method of real attenuation of informative signal of video subsystem of electron-ray tube monitor measurement is described and confirmed in experiment. The measurements were made using specialized automatized system “Sigurd” and video subsystem informative signal noise generator. The described method allows a significant reduction of  the time needed for specialized investigations of security verification on electromagnetic emanation.

  3. Roles for gut vagal sensory signals in determining energy availability and energy expenditure.

    Science.gov (United States)

    Schwartz, Gary J

    2018-08-15

    The gut sensory vagus transmits a wide range of meal-related mechanical, chemical and gut peptide signals from gastrointestinal and hepatic tissues to the central nervous system at the level of the caudal brainstem. Results from studies using neurophysiological, behavioral physiological and metabolic approaches that challenge the integrity of this gut-brain axis support an important role for these gut signals in the negative feedback control of energy availability by limiting food intake during a meal. These experimental approaches have now been applied to identify important and unanticipated contributions of the vagal sensory gut-brain axis to the control of two additional effectors of overall energy balance: the feedback control of endogenous energy availability through hepatic glucose production and metabolism, and the control of energy expenditure through brown adipose tissue thermogenesis. Taken together, these studies reveal the pleiotropic influences of gut vagal meal-related signals on energy balance, and encourage experimental efforts aimed at understanding how the brainstem represents, organizes and coordinates gut vagal sensory signals with these three determinants of energy homeostasis. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Interplay between glucose and leptin signalling determines the strength of GABAergic synapses at POMC neurons.

    Science.gov (United States)

    Lee, Dong Kun; Jeong, Jae Hoon; Chun, Sung-Kun; Chua, Streamson; Jo, Young-Hwan

    2015-03-26

    Regulation of GABAergic inhibitory inputs and alterations in POMC neuron activity by nutrients and adiposity signals regulate energy and glucose homeostasis. Thus, understanding how POMC neurons integrate these two signal molecules at the synaptic level is important. Here we show that leptin's action on GABA release to POMC neurons is influenced by glucose levels. Leptin stimulates the JAK2-PI3K pathway in both presynaptic GABAergic terminals and postsynaptic POMC neurons. Inhibition of AMPK activity in presynaptic terminals decreases GABA release at 10 mM glucose. However, postsynaptic TRPC channel opening by the PI3K-PLC signalling pathway in POMC neurons enhances spontaneous GABA release via activation of presynaptic MC3/4 and mGlu receptors at 2.5 mM glucose. High-fat feeding blunts AMPK-dependent presynaptic inhibition, whereas PLC-mediated GABAergic feedback inhibition remains responsive to leptin. Our data indicate that the interplay between glucose and leptin signalling in glutamatergic POMC neurons is critical for determining the strength of inhibitory tone towards POMC neurons.

  5. Interplay between glucose and leptin signaling determines the strength of GABAergic synapses at POMC neurons

    Science.gov (United States)

    Lee, Dong Kun; Jeong, Jae Hoon; Chun, Sung-Kun; Chua, Streamson; Jo, Young-Hwan

    2015-01-01

    Regulation of GABAergic inhibitory inputs and alterations in POMC neuron activity by nutrients and adiposity signals regulate energy and glucose homeostasis. Thus, understanding how POMC neurons integrate these two signal molecules at the synaptic level is important. Here we show that leptin’s action on GABA release to POMC neurons is influenced by glucose levels. Leptin stimulates the JAK2-PI3K pathway in both presynaptic GABAergic terminals and postsynaptic POMC neurons. Inhibition of AMPK activity in presynaptic terminals decreases GABA release at 10 mM glucose. However, postsynaptic TRPC channel opening by the PI3K-PLC signaling pathway in POMC neurons enhances spontaneous GABA release via activation of presynaptic MC3/4 and mGlu receptors at 2.5 mM glucose. High-fat feeding blunts AMPK-dependent presynaptic inhibition, whereas PLC-mediated GABAergic feedback inhibition remains responsive to leptin. Our data indicate that the interplay between glucose and leptin signaling in glutamatergic POMC neurons is critical for determining the strength of inhibitory tone towards POMC neurons. PMID:25808323

  6. ALFY-Controlled DVL3 Autophagy Regulates Wnt Signaling, Determining Human Brain Size.

    Directory of Open Access Journals (Sweden)

    Rotem Kadir

    2016-03-01

    Full Text Available Primary microcephaly is a congenital neurodevelopmental disorder of reduced head circumference and brain volume, with fewer neurons in the cortex of the developing brain due to premature transition between symmetrical and asymmetrical cellular division of the neuronal stem cell layer during neurogenesis. We now show through linkage analysis and whole exome sequencing, that a dominant mutation in ALFY, encoding an autophagy scaffold protein, causes human primary microcephaly. We demonstrate the dominant effect of the mutation in drosophila: transgenic flies harboring the human mutant allele display small brain volume, recapitulating the disease phenotype. Moreover, eye-specific expression of human mutant ALFY causes rough eye phenotype. In molecular terms, we demonstrate that normally ALFY attenuates the canonical Wnt signaling pathway via autophagy-dependent removal specifically of aggregates of DVL3 and not of Dvl1 or Dvl2. Thus, autophagic attenuation of Wnt signaling through removal of Dvl3 aggregates by ALFY acts in determining human brain size.

  7. Disentangling evolutionary signals: conservation, specificity determining positions and coevolution. Implication for catalytic residue prediction

    DEFF Research Database (Denmark)

    Teppa, Elin; Wilkins, Angela D.; Nielsen, Morten

    2012-01-01

    Background: A large panel of methods exists that aim to identify residues with critical impact on protein function based on evolutionary signals, sequence and structure information. However, it is not clear to what extent these different methods overlap, and if any of the methods have higher...... predictive potential compared to others when it comes to, in particular, the identification of catalytic residues (CR) in proteins. Using a large set of enzymatic protein families and measures based on different evolutionary signals, we sought to break up the different components of the information content......-value Evolutionary Trace (rvET) methods and conservation, another containing mutual information (MI) methods, and the last containing methods designed explicitly for the identification of specificity determining positions (SDPs): integer-value Evolutionary Trace (ivET), SDPfox, and XDET. In terms of prediction of CR...

  8. Conformal field theory in conformal space

    International Nuclear Information System (INIS)

    Preitschopf, C.R.; Vasiliev, M.A.

    1999-01-01

    We present a new framework for a Lagrangian description of conformal field theories in various dimensions based on a local version of d + 2-dimensional conformal space. The results include a true gauge theory of conformal gravity in d = (1, 3) and any standard matter coupled to it. An important feature is the automatic derivation of the conformal gravity constraints, which are necessary for the analysis of the matter systems

  9. Rates and equilibrium constants of the ligand-induced conformational transition of an HCN ion channel protein domain determined by DEER spectroscopy.

    Science.gov (United States)

    Collauto, Alberto; DeBerg, Hannah A; Kaufmann, Royi; Zagotta, William N; Stoll, Stefan; Goldfarb, Daniella

    2017-06-14

    Ligand binding can induce significant conformational changes in proteins. The mechanism of this process couples equilibria associated with the ligand binding event and the conformational change. Here we show that by combining the application of W-band double electron-electron resonance (DEER) spectroscopy with microfluidic rapid freeze quench (μRFQ) it is possible to resolve these processes and obtain both equilibrium constants and reaction rates. We studied the conformational transition of the nitroxide labeled, isolated carboxy-terminal cyclic-nucleotide binding domain (CNBD) of the HCN2 ion channel upon binding of the ligand 3',5'-cyclic adenosine monophosphate (cAMP). Using model-based global analysis, the time-resolved data of the μRFQ DEER experiments directly provide fractional populations of the open and closed conformations as a function of time. We modeled the ligand-induced conformational change in the protein using a four-state model: apo/open (AO), apo/closed (AC), bound/open (BO), bound/closed (BC). These species interconvert according to AC + L ⇌ AO + L ⇌ BO ⇌ BC. By analyzing the concentration dependence of the relative contributions of the closed and open conformations at equilibrium, we estimated the equilibrium constants for the two conformational equilibria and the open-state ligand dissociation constant. Analysis of the time-resolved μRFQ DEER data gave estimates for the intrinsic rates of ligand binding and unbinding as well as the rates of the conformational change. This demonstrates that DEER can quantitatively resolve both the thermodynamics and the kinetics of ligand binding and the associated conformational change.

  10. Variable-temperature NMR and conformational analysis of Oenothein B

    International Nuclear Information System (INIS)

    Santos, Suzana C.; Carvalho, Ariadne G.; Fortes, Gilmara A.C.; Ferri, Pedro H.; Oliveira, Anselmo E. de

    2014-01-01

    Oenothein B is a dimeric hydrolyzable tannin with a wide range of biological activities, such as antitumour, anti-inflammatory and antiviral. Its nuclear magnetic resonance (NMR) at room temperature show duplications and broadening of signals. Experiments of 1D and 2D NMR at lower temperatures were useful for the complete NMR assignments of all hydrogens and carbons. The 3D structure of the most stable conformer was determined for the first time by nuclear Overhauser effect spectroscopy (NOESY) experiment (-20 deg C) and density functional theory (DFT)(B3LYP/6-31G)/ polarizable continuum model (PCM) quantum chemical calculations. The favoured conformation showed a highly compacted geometry and a lack of symmetry, in which the two valoneoyl groups showed distinct conformational parameters and stabilities. (author)

  11. Variable-temperature NMR and conformational analysis of Oenothein B

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Suzana C.; Carvalho, Ariadne G.; Fortes, Gilmara A.C.; Ferri, Pedro H.; Oliveira, Anselmo E. de, [Universidade Federal de Goias (UFGO), Goiania, GO (Brazil). Instituto de Quimica

    2014-02-15

    Oenothein B is a dimeric hydrolyzable tannin with a wide range of biological activities, such as antitumour, anti-inflammatory and antiviral. Its nuclear magnetic resonance (NMR) at room temperature show duplications and broadening of signals. Experiments of 1D and 2D NMR at lower temperatures were useful for the complete NMR assignments of all hydrogens and carbons. The 3D structure of the most stable conformer was determined for the first time by nuclear Overhauser effect spectroscopy (NOESY) experiment (-20 deg C) and density functional theory (DFT)(B3LYP/6-31G)/ polarizable continuum model (PCM) quantum chemical calculations. The favoured conformation showed a highly compacted geometry and a lack of symmetry, in which the two valoneoyl groups showed distinct conformational parameters and stabilities. (author)

  12. Conformational analysis of an acyclic tetrapeptide: ab-initio structure determination from X-ray powder diffraction, Hirshfeld surface analysis and electronic structure.

    Science.gov (United States)

    Das, Uday; Naskar, Jishu; Mukherjee, Alok Kumar

    2015-12-01

    A terminally protected acyclic tetrapeptide has been synthesized, and the crystal structure of its hydrated form, Boc-Tyr-Aib-Tyr-Ile-OMe·2H2O (1), has been determined directly from powder X-ray diffraction data. The backbone conformation of tetrapeptide (1) exhibiting two consecutive β-turns is stabilized by two 4 → 1 intramolecular N-H · · · O hydrogen bonds. In the crystalline state, the tetrapeptide molecules are assembled through water-mediated O-H · · · O hydrogen bonds to form two-dimensional molecular sheets, which are further linked by intermolecular C-H · · · O hydrogen bonds into a three-dimensional supramolecular framework. The molecular electrostatic potential (MEP) surface of (1) has been used to supplement the crystallographic observations. The nature of intermolecular interactions in (1) has been analyzed quantitatively through the Hirshfeld surface and two-dimensional fingerprint plot. The DFT optimized molecular geometry of (1) agrees closely with that obtained from the X-ray structure analysis. The present structure analysis of Boc-Tyr-Aib-Tyr-Ile-OMe·2H2 O (1) represents a case where ab-initio crystal structure of an acyclic tetrapeptide with considerable molecular flexibility has been accomplished from laboratory X-ray powder diffraction data. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.

  13. Ring-to-chain conformation may be a determining factor in the ability of xanthophylls to bind to the bulk light-harvesting complex of plants

    Science.gov (United States)

    Young, Andrew J.; Phillip, Denise M.; Hashimoto, Hideki

    2002-12-01

    The binding of xanthophylls to the main light-harvesting complex (LHC) of higher plants has been studied using the technique of in vitro reconstitution. This demonstrated that the carotenoid diol lactucaxanthin (native to many LHC) would not support the assembly of LHC whilst other diols, notably zeaxanthin and lutein would. Analysis of the most stable forms of the carotenoid end-groups found in xanthophylls native to higher plant LHC (as determined by theoretical calculations) revealed profound differences in the adiabatic potential energy curves for the C5-C6-C7-C8-torsion angle for the ɛ end-groups in lactucaxanthin (6-s- trans), in comparison to carotenoids possessing a 3-hydroxy β end-group (zeaxanthin; 6-s- cis), 3-hydroxy-4-keto β end-group (astaxanthin, 6-s- cis) or a 3-hydroxy-5,6-epoxy end-group (violaxanthin, distorted 6-s- cis). The (ɛ end-groups of other carotenoids studied were 6-s- trans. We examine the possible relationship between carotenoid ring-to-chain conformation and binding to LHC.

  14. The Role of Retinal Determination Gene Network (RDGN) in Hormone Signaling Transduction and Prostate Tumorigenes

    Science.gov (United States)

    2015-12-01

    S, Zhang W, Zhou J, Wang J, Ertel A, Li Z, Rui H, Quong A, Lisanti MP, Tozeren A, Tanes C, Addya S, Gormley M, Wang C, McMahon SB, Pestell RG...MP, Wang C, Pestell RG. Acetylation of the cell-fate factor dachshund determines p53 binding and signaling modules in breast cancer. Oncotarget...MP, Quong A, Ertel A, Pestell RG. Cell fate factor DACH1 represses YB-1-mediated oncogenic transcription and translation. Cancer Res. 2014;74(3):829

  15. Attitude determination for small satellites using GPS signal-to-noise ratio

    Science.gov (United States)

    Peters, Daniel

    An embedded system for GPS-based attitude determination (AD) using signal-to-noise (SNR) measurements was developed for CubeSat applications. The design serves as an evaluation testbed for conducting ground based experiments using various computational methods and antenna types to determine the optimum AD accuracy. Raw GPS data is also stored to non-volatile memory for downloading and post analysis. Two low-power microcontrollers are used for processing and to display information on a graphic screen for real-time performance evaluations. A new parallel inter-processor communication protocol was developed that is faster and uses less power than existing standard protocols. A shorted annular patch (SAP) antenna was fabricated for the initial ground-based AD experiments with the testbed. Static AD estimations with RMS errors in the range of 2.5° to 4.8° were achieved over a range of off-zenith attitudes.

  16. Micro-earthquake signal analysis and hypocenter determination around Lokon volcano complex

    Energy Technology Data Exchange (ETDEWEB)

    Firmansyah, Rizky, E-mail: rizkyfirmansyah@hotmail.com [Geophysical Engineering, Faculty of Mining and Petroleum Engineering, Institut Teknologi Bandung, Bandung, 40132 (Indonesia); Nugraha, Andri Dian, E-mail: nugraha@gf.itb.ac.id [Global Geophysical Group, Faculty of Mining and Petroleum Engineering, Institut Teknologi Bandung, Bandung, 40132 (Indonesia); Kristianto, E-mail: kris@vsi.esdm.go.id [Center for Volcanology and Geological Hazard Mitigation (CVGHM), Geological Agency, Bandung, 40122 (Indonesia)

    2015-04-24

    Mount Lokon is one of five active volcanoes which is located in the North Sulawesi region. Since June 26{sup th}, 2011, standby alert set by the Center for Volcanology and Geological Hazard Mitigation (CVGHM) for this mountain. The Mount Lokon volcano erupted on July 4{sup th}, 2011 and still continuously erupted until August 28{sup th}, 2011. Due to its high seismic activity, this study is focused to analysis of micro-earthquake signal and determine the micro-earthquake hypocenter location around the complex area of Lokon-Empung Volcano before eruption phase in 2011 (time periods of January, 2009 up to March, 2010). Determination of the hypocenter location was conducted with Geiger Adaptive Damping (GAD) method. We used initial model from previous study in Volcan de Colima, Mexico. The reason behind the model selection was based on the same characteristics that shared between Mount Lokon and Colima including andesitic stratovolcano and small-plinian explosions volcanian types. In this study, a picking events was limited to the volcano-tectonics of A and B types, hybrid, long-period that has a clear signal onset, and local tectonic with different maximum S – P time are not more than three seconds. As a result, we observed the micro-earthquakes occurred in the area north-west of Mount Lokon region.

  17. Micro-earthquake signal analysis and hypocenter determination around Lokon volcano complex

    International Nuclear Information System (INIS)

    Firmansyah, Rizky; Nugraha, Andri Dian; Kristianto

    2015-01-01

    Mount Lokon is one of five active volcanoes which is located in the North Sulawesi region. Since June 26 th , 2011, standby alert set by the Center for Volcanology and Geological Hazard Mitigation (CVGHM) for this mountain. The Mount Lokon volcano erupted on July 4 th , 2011 and still continuously erupted until August 28 th , 2011. Due to its high seismic activity, this study is focused to analysis of micro-earthquake signal and determine the micro-earthquake hypocenter location around the complex area of Lokon-Empung Volcano before eruption phase in 2011 (time periods of January, 2009 up to March, 2010). Determination of the hypocenter location was conducted with Geiger Adaptive Damping (GAD) method. We used initial model from previous study in Volcan de Colima, Mexico. The reason behind the model selection was based on the same characteristics that shared between Mount Lokon and Colima including andesitic stratovolcano and small-plinian explosions volcanian types. In this study, a picking events was limited to the volcano-tectonics of A and B types, hybrid, long-period that has a clear signal onset, and local tectonic with different maximum S – P time are not more than three seconds. As a result, we observed the micro-earthquakes occurred in the area north-west of Mount Lokon region

  18. Net Analyte Signal Standard Additions Method for Simultaneous Determination of Sulfamethoxazole and Trimethoprim in Pharmaceutical Formulations and Biological Fluids

    OpenAIRE

    Givianrad, M. H.; Mohagheghian, M.

    2012-01-01

    The applicability of a novel net analyte signal standard addition method (NASSAM) to the resolving of overlapping spectra corresponding to the sulfamethoxazole and trimethoprim was verified by UV-visible spectrophotometry. The results confirmed that the net analyte signal standard additions method with simultaneous addition of both analytes is suitable for the simultaneous determination of sulfamethoxazole and trimethoprim in aqueous media. Moreover, applying the net analyte signal standard a...

  19. Riemann monodromy problem and conformal field theories

    International Nuclear Information System (INIS)

    Blok, B.

    1989-01-01

    A systematic analysis of the use of the Riemann monodromy problem for determining correlators (conformal blocks) on the sphere is presented. The monodromy data is constructed in terms of the braid matrices and gives a constraint on the noninteger part of the conformal dimensions of the primary fields. To determine the conformal blocks we need to know the order of singularities. We establish a criterion which tells us when the knowledge of the conformal dimensions of primary fields suffice to determine the blocks. When zero modes of the extended algebra are present the analysis is more difficult. In this case we give a conjecture that works for the SU(2) WZW case. (orig.)

  20. Direct Position Determination of Unknown Signals in the Presence of Multipath Propagation.

    Science.gov (United States)

    Du, Jianping; Wang, Ding; Yu, Wanting; Yu, Hongyi

    2018-03-17

    A novel geolocation architecture, termed "Multiple Transponders and Multiple Receivers for Multiple Emitters Positioning System (MTRE)" is proposed in this paper. Existing Direct Position Determination (DPD) methods take advantage of a rather simple channel assumption (line of sight channels with complex path attenuations) and a simplified MUltiple SIgnal Classification (MUSIC) algorithm cost function to avoid the high dimension searching. We point out that the simplified assumption and cost function reduce the positioning accuracy because of the singularity of the array manifold in a multi-path environment. We present a DPD model for unknown signals in the presence of Multi-path Propagation (MP-DPD) in this paper. MP-DPD adds non-negative real path attenuation constraints to avoid the mistake caused by the singularity of the array manifold. The Multi-path Propagation MUSIC (MP-MUSIC) method and the Active Set Algorithm (ASA) are designed to reduce the dimension of searching. A Multi-path Propagation Maximum Likelihood (MP-ML) method is proposed in addition to overcome the limitation of MP-MUSIC in the sense of a time-sensitive application. An iterative algorithm and an approach of initial value setting are given to make the MP-ML time consumption acceptable. Numerical results validate the performances improvement of MP-MUSIC and MP-ML. A closed form of the Cramér-Rao Lower Bound (CRLB) is derived as a benchmark to evaluate the performances of MP-MUSIC and MP-ML.

  1. Induction of type I interferon signaling determines the relative pathogenicity of Staphylococcus aureus strains.

    Directory of Open Access Journals (Sweden)

    Dane Parker

    2014-02-01

    Full Text Available The tremendous success of S. aureus as a human pathogen has been explained primarily by its array of virulence factors that enable the organism to evade host immunity. Perhaps equally important, but less well understood, is the importance of the intensity of the host response in determining the extent of pathology induced by S. aureus infection, particularly in the pathogenesis of pneumonia. We compared the pathogenesis of infection caused by two phylogenetically and epidemiologically distinct strains of S. aureus whose behavior in humans has been well characterized. Induction of the type I IFN cascade by strain 502A, due to a NOD2-IRF5 pathway, was the major factor in causing severe pneumonia and death in a murine model of pneumonia and was associated with autolysis and release of peptidogylcan. In contrast to USA300, 502A was readily eliminated from epithelial surfaces in vitro. Nonetheless, 502A caused significantly increased tissue damage due to the organisms that were able to invade systemically and trigger type I IFN responses, and this was ameliorated in Ifnar⁻/⁻ mice. The success of USA300 to cause invasive infection appears to depend upon its resistance to eradication from epithelial surfaces, but not production of specific toxins. Our studies illustrate the important and highly variable role of type I IFN signaling within a species and suggest that targeted immunomodulation of specific innate immune signaling cascades may be useful to prevent the excessive morbidity associated with S. aureus pneumonia.

  2. A set of enhanced green fluorescent protein concatemers for quantitative determination of nuclear localization signal strength.

    Science.gov (United States)

    Böhm, Jennifer; Thavaraja, Ramya; Giehler, Susanne; Nalaskowski, Marcus M

    2017-09-15

    Regulated transport of proteins between nucleus and cytoplasm is an important process in the eukaryotic cell. In most cases, active nucleo-cytoplasmic protein transport is mediated by nuclear localization signal (NLS) and/or nuclear export signal (NES) motifs. In this study, we developed a set of vectors expressing enhanced GFP (EGFP) concatemers ranging from 2 to 12 subunits (2xEGFP to 12xEGFP) for analysis of NLS strength. As shown by in gel GFP fluorescence analysis and αGFP Western blotting, EGFP concatemers are expressed as fluorescent full-length proteins in eukaryotic cells. As expected, nuclear localization of concatemeric EGFPs decreases with increasing molecular weight. By oligonucleotide ligation this set of EGFP concatemers can be easily fused to NLS motifs. After determination of intracellular localization of EGFP concatemers alone and fused to different NLS motifs we calculated the size of a hypothetic EGFP concatemer showing a defined distribution of EGFP fluorescence between nucleus and cytoplasm (n/c ratio = 2). Clear differences of the size of the hypothetic EGFP concatemer depending on the fused NLS motif were observed. Therefore, we propose to use the size of this hypothetic concatemer as quantitative indicator for comparing strength of different NLS motifs. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Distinct Phosphorylation Clusters Determine the Signaling Outcome of Free Fatty Acid Receptor 4/G Protein-Coupled Receptor 120

    DEFF Research Database (Denmark)

    Prihandoko, Rudi; Alvarez-Curto, Elisa; Hudson, Brian D

    2016-01-01

    of these phosphoacceptor sites to alanine completely prevented phosphorylation of mFFA4 but did not limit receptor coupling to extracellular signal regulated protein kinase 1 and 2 (ERK1/2) activation. Rather, an inhibitor of Gq/11proteins completely prevented receptor signaling to ERK1/2. By contrast, the recruitment...... activation. These unique observations define differential effects on signaling mediated by phosphorylation at distinct locations. This hallmark feature supports the possibility that the signaling outcome of mFFA4 activation can be determined by the pattern of phosphorylation (phosphorylation barcode...

  4. Conformational preludes to the latency transition in PAI-1 as determined by atomistic computer simulations and hydrogen/deuterium-exchange mass spectrometry

    DEFF Research Database (Denmark)

    Petersen, Michael; Madsen, Jeppe B; Jørgensen, Thomas J D

    2017-01-01

    activator inhibitor 1 (PAI-1). We report the first multi-microsecond atomistic molecular dynamics simulations of PAI-1 and compare the data with experimental hydrogen/deuterium-exchange data (HDXMS). The simulations reveal notable conformational flexibility of helices D, E and F and major fluctuations...... are observed in the W86-loop which occasionally leads to progressive detachment of β-strand 2 A from β-strand 3 A. An interesting correlation between Cα-RMSD values from simulations and experimental HDXMS data is observed. Helices D, E and F are known to be important for the overall stability of active PAI-1......Both function and dysfunction of serine protease inhibitors (serpins) involve massive conformational change in their tertiary structure but the dynamics facilitating these events remain poorly understood. We have studied the dynamic preludes to conformational change in the serpin plasminogen...

  5. Determination of elastic mechanical characteristics of surface coatings from analysis of signals obtained by impulse excitation

    Science.gov (United States)

    Nyaguly, E.; Craştiu, I.; Deac, S.; Gozman-Pop, C.; Drăgănescu, G.; Bereteu, L.

    2018-01-01

    Most of the surface coatings are based on the synthetic polymers, which are substances composed from very large molecules that form tough, flexible, adhesive films when applied to surfaces. The other components of surface coverings materials are pigments that provide colour, opacity, gloss and other properties. Surface coatings are two-phase composite materials: constitute a polymer matrix on the one side, and on the other side of the pigments and additives dispersed in the matrix. Their role is not only aesthetically but also to ensure anticorrosive protection or even improve some mechanical properties of coated surfaces. In this paper it will follow, starting from the mechanical properties of the substrate, the metallic sheet in general, to determine the new properties of the assembly of substrate and the two coating layers, also the determination of mechanical properties of the layers. From the analysis of vibroacoustic signals obtained by the impulse excitation of the sample, one can determine the elasticity modulus. These results come to validate the results based on finite element analysis (FEA) of the same samples.

  6. Use of high frequency analysis of acoustic emission signals to determine rolling element bearing condition

    International Nuclear Information System (INIS)

    Cockerill, A; Holford, K M; Pullin, R; Clarke, A; Bradshaw, T; Cole, P

    2015-01-01

    Acoustic Emission (AE) sensors were used to detect signals arising from a cylindrical roller bearing with artificial defects seeded onto the outer raceway. An SKF N204ECP roller bearing was placed between two double row spherical roller bearings, type SKF 22202E, and loaded between 0.29 and 1.79kN. Speed was constant at 5780rpm. High frequency analysis allowed insight into the condition of the bearings through the determination of an increase in the structural resonances of the system as the size of an artificial defect was increased. As higher loads were applied, frequencies around 100kHz were excited, indicating the release of AE possibly attributed to friction and the plastic deformation as peaks, induced through engraving of the raceway, were flattened and worn down. Sensitivity of AE to this level in bearings indicates the potential of the technique to detect the early stages of bearing failure during life tests. (paper)

  7. A method to determine the necessity for global signal regression in resting-state fMRI studies.

    Science.gov (United States)

    Chen, Gang; Chen, Guangyu; Xie, Chunming; Ward, B Douglas; Li, Wenjun; Antuono, Piero; Li, Shi-Jiang

    2012-12-01

    In resting-state functional MRI studies, the global signal (operationally defined as the global average of resting-state functional MRI time courses) is often considered a nuisance effect and commonly removed in preprocessing. This global signal regression method can introduce artifacts, such as false anticorrelated resting-state networks in functional connectivity analyses. Therefore, the efficacy of this technique as a correction tool remains questionable. In this article, we establish that the accuracy of the estimated global signal is determined by the level of global noise (i.e., non-neural noise that has a global effect on the resting-state functional MRI signal). When the global noise level is low, the global signal resembles the resting-state functional MRI time courses of the largest cluster, but not those of the global noise. Using real data, we demonstrate that the global signal is strongly correlated with the default mode network components and has biological significance. These results call into question whether or not global signal regression should be applied. We introduce a method to quantify global noise levels. We show that a criteria for global signal regression can be found based on the method. By using the criteria, one can determine whether to include or exclude the global signal regression in minimizing errors in functional connectivity measures. Copyright © 2012 Wiley Periodicals, Inc.

  8. Multi-signal sedimentation velocity analysis with mass conservation for determining the stoichiometry of protein complexes.

    Directory of Open Access Journals (Sweden)

    Chad A Brautigam

    Full Text Available Multi-signal sedimentation velocity analytical ultracentrifugation (MSSV is a powerful tool for the determination of the number, stoichiometry, and hydrodynamic shape of reversible protein complexes in two- and three-component systems. In this method, the evolution of sedimentation profiles of macromolecular mixtures is recorded simultaneously using multiple absorbance and refractive index signals and globally transformed into both spectrally and diffusion-deconvoluted component sedimentation coefficient distributions. For reactions with complex lifetimes comparable to the time-scale of sedimentation, MSSV reveals the number and stoichiometry of co-existing complexes. For systems with short complex lifetimes, MSSV reveals the composition of the reaction boundary of the coupled reaction/migration process, which we show here may be used to directly determine an association constant. A prerequisite for MSSV is that the interacting components are spectrally distinguishable, which may be a result, for example, of extrinsic chromophores or of different abundances of aromatic amino acids contributing to the UV absorbance. For interacting components that are spectrally poorly resolved, here we introduce a method for additional regularization of the spectral deconvolution by exploiting approximate knowledge of the total loading concentrations. While this novel mass conservation principle does not discriminate contributions to different species, it can be effectively combined with constraints in the sedimentation coefficient range of uncomplexed species. We show in theory, computer simulations, and experiment, how mass conservation MSSV as implemented in SEDPHAT can enhance or even substitute for the spectral discrimination of components. This should broaden the applicability of MSSV to the analysis of the composition of reversible macromolecular complexes.

  9. Conformational Clusters of Phosphorylated Tyrosine.

    Science.gov (United States)

    Abdelrasoul, Maha; Ponniah, Komala; Mao, Alice; Warden, Meghan S; Elhefnawy, Wessam; Li, Yaohang; Pascal, Steven M

    2017-12-06

    Tyrosine phosphorylation plays an important role in many cellular and intercellular processes including signal transduction, subcellular localization, and regulation of enzymatic activity. In 1999, Blom et al., using the limited number of protein data bank (PDB) structures available at that time, reported that the side chain structures of phosphorylated tyrosine (pY) are partitioned into two conserved conformational clusters ( Blom, N.; Gammeltoft, S.; Brunak, S. J. Mol. Biol. 1999 , 294 , 1351 - 1362 ). We have used the spectral clustering algorithm to cluster the increasingly growing number of protein structures with pY sites, and have found that the pY residues cluster into three distinct side chain conformations. Two of these pY conformational clusters associate strongly with a narrow range of tyrosine backbone conformation. The novel cluster also highly correlates with the identity of the n + 1 residue, and is strongly associated with a sequential pYpY conformation which places two adjacent pY side chains in a specific relative orientation. Further analysis shows that the three pY clusters are associated with distinct distributions of cognate protein kinases.

  10. Linear signal noise summer accurately determines and controls S/N ratio

    Science.gov (United States)

    Sundry, J. L.

    1966-01-01

    Linear signal noise summer precisely controls the relative power levels of signal and noise, and mixes them linearly in accurately known ratios. The S/N ratio accuracy and stability are greatly improved by this technique and are attained simultaneously.

  11. Operator algebras and conformal field theory

    International Nuclear Information System (INIS)

    Gabbiani, F.; Froehlich, J.

    1993-01-01

    We define and study two-dimensional, chiral conformal field theory by the methods of algebraic field theory. We start by characterizing the vacuum sectors of such theories and show that, under very general hypotheses, their algebras of local observables are isomorphic to the unique hyperfinite type III 1 factor. The conformal net determined by the algebras of local observables is proven to satisfy Haag duality. The representation of the Moebius group (and presumably of the entire Virasoro algebra) on the vacuum sector of a conformal field theory is uniquely determined by the Tomita-Takesaki modular operators associated with its vacuum state and its conformal net. We then develop the theory of Mebius covariant representations of a conformal net, using methods of Doplicher, Haag and Roberts. We apply our results to the representation theory of loop groups. Our analysis is motivated by the desire to find a 'background-independent' formulation of conformal field theories. (orig.)

  12. Turnover of amyloid precursor protein family members determines their nuclear signaling capability.

    Science.gov (United States)

    Gersbacher, Manuel T; Goodger, Zoë V; Trutzel, Annette; Bundschuh, Diana; Nitsch, Roger M; Konietzko, Uwe

    2013-01-01

    The amyloid precursor protein (APP) as well as its homologues, APP-like protein 1 and 2 (APLP1 and APLP2), are cleaved by α-, β-, and γ-secretases, resulting in the release of their intracellular domains (ICDs). We have shown that the APP intracellular domain (AICD) is transported to the nucleus by Fe65 where they jointly bind the histone acetyltransferase Tip60 and localize to spherical nuclear complexes (AFT complexes), which are thought to be sites of transcription. We have now analyzed the subcellular localization and turnover of the APP family members. Similarly to AICD, the ICD of APLP2 localizes to spherical nuclear complexes together with Fe65 and Tip60. In contrast, the ICD of APLP1, despite binding to Fe65, does not translocate to the nucleus. In addition, APLP1 predominantly localizes to the plasma membrane, whereas APP and APLP2 are detected in vesicular structures. APLP1 also demonstrates a much slower turnover of the full-length protein compared to APP and APLP2. We further show that the ICDs of all APP family members are degraded by the proteasome and that the N-terminal amino acids of ICDs determine ICD degradation rate. Together, our results suggest that different nuclear signaling capabilities of APP family members are due to different rates of full-length protein processing and ICD proteasomal degradation. Our results provide evidence in support of a common nuclear signaling function for APP and APLP2 that is absent in APLP1, but suggest that APLP1 has a regulatory role in the nuclear translocation of APP family ICDs due to the sequestration of Fe65.

  13. Direct Position Determination of Unknown Signals in the Presence of Multipath Propagation

    Science.gov (United States)

    Yu, Hongyi

    2018-01-01

    A novel geolocation architecture, termed “Multiple Transponders and Multiple Receivers for Multiple Emitters Positioning System (MTRE)” is proposed in this paper. Existing Direct Position Determination (DPD) methods take advantage of a rather simple channel assumption (line of sight channels with complex path attenuations) and a simplified MUltiple SIgnal Classification (MUSIC) algorithm cost function to avoid the high dimension searching. We point out that the simplified assumption and cost function reduce the positioning accuracy because of the singularity of the array manifold in a multi-path environment. We present a DPD model for unknown signals in the presence of Multi-path Propagation (MP-DPD) in this paper. MP-DPD adds non-negative real path attenuation constraints to avoid the mistake caused by the singularity of the array manifold. The Multi-path Propagation MUSIC (MP-MUSIC) method and the Active Set Algorithm (ASA) are designed to reduce the dimension of searching. A Multi-path Propagation Maximum Likelihood (MP-ML) method is proposed in addition to overcome the limitation of MP-MUSIC in the sense of a time-sensitive application. An iterative algorithm and an approach of initial value setting are given to make the MP-ML time consumption acceptable. Numerical results validate the performances improvement of MP-MUSIC and MP-ML. A closed form of the Cramér–Rao Lower Bound (CRLB) is derived as a benchmark to evaluate the performances of MP-MUSIC and MP-ML. PMID:29562601

  14. Direct Position Determination of Unknown Signals in the Presence of Multipath Propagation

    Directory of Open Access Journals (Sweden)

    Jianping Du

    2018-03-01

    Full Text Available A novel geolocation architecture, termed “Multiple Transponders and Multiple Receivers for Multiple Emitters Positioning System (MTRE” is proposed in this paper. Existing Direct Position Determination (DPD methods take advantage of a rather simple channel assumption (line of sight channels with complex path attenuations and a simplified MUltiple SIgnal Classification (MUSIC algorithm cost function to avoid the high dimension searching. We point out that the simplified assumption and cost function reduce the positioning accuracy because of the singularity of the array manifold in a multi-path environment. We present a DPD model for unknown signals in the presence of Multi-path Propagation (MP-DPD in this paper. MP-DPD adds non-negative real path attenuation constraints to avoid the mistake caused by the singularity of the array manifold. The Multi-path Propagation MUSIC (MP-MUSIC method and the Active Set Algorithm (ASA are designed to reduce the dimension of searching. A Multi-path Propagation Maximum Likelihood (MP-ML method is proposed in addition to overcome the limitation of MP-MUSIC in the sense of a time-sensitive application. An iterative algorithm and an approach of initial value setting are given to make the MP-ML time consumption acceptable. Numerical results validate the performances improvement of MP-MUSIC and MP-ML. A closed form of the Cramér–Rao Lower Bound (CRLB is derived as a benchmark to evaluate the performances of MP-MUSIC and MP-ML.

  15. Brain serotonin signaling does not determine sexual preference in male mice.

    Directory of Open Access Journals (Sweden)

    Mariana Angoa-Pérez

    Full Text Available It was reported recently that male mice lacking brain serotonin (5-HT lose their preference for females (Liu et al., 2011, Nature, 472, 95-100, suggesting a role for 5-HT signaling in sexual preference. Regulation of sex preference by 5-HT lies outside of the well established roles in this behavior established for the vomeronasal organ (VNO and the main olfactory epithelium (MOE. Presently, mice with a null mutation in the gene for tryptophan hydroxylase 2 (TPH2, which are depleted of brain 5-HT, were tested for sexual preference. When presented with inanimate (urine scents from male or estrous female or animate (male or female mouse in estrus sexual stimuli, TPH2-/- males show a clear preference for female over male stimuli. When a TPH2-/- male is offered the simultaneous choice between an estrous female and a male mouse, no sexual preference is expressed. However, when confounding behaviors that are seen among 3 mice in the same cage are controlled, TPH2-/- mice, like their TPH2+/+ counterparts, express a clear preference for female mice. Female TPH2-/- mice are preferred by males over TPH2+/+ females but this does not lead to increased pregnancy success. In fact, if one or both partners in a mating pair are TPH2-/- in genotype, pregnancy success rates are significantly decreased. Finally, expression of the VNO-specific cation channel TRPC2 and of CNGA2 in the MOE of TPH2-/- mice is normal, consistent with behavioral findings that sexual preference of TPH2-/- males for females is intact. In conclusion, 5-HT signaling in brain does not determine sexual preference in male mice. The use of pharmacological agents that are non-selective for the 5-HT neuronal system and that have serious adverse effects may have contributed historically to the stance that 5-HT regulates sexual behavior, including sex partner preference.

  16. Processing and display of nuclear magnetism logging signals: application to residual oil determination

    International Nuclear Information System (INIS)

    Brown, R.J.S.; Neuman, C.H.

    1980-01-01

    A presentation is made of a series of computations and signal displays which help to show the nature of NML signals in general as well as to show the response to particular formation, hole, and tool conditions. Such processing of digitally recorded signals enables improved accuracy and bed resolution over that presented with the raw log. The treatment of drilling mud filtrate to eliminate NML signal from the brine phase in the invaded zone is described. Logs are shown as recorded before and after invasion of treated mud filtrate. This treatment causes the NML signal to correspond to residual oil only, enabling accurate and relatively inexpensive measurement of residual oil. 24 refs

  17. NMR and computer modelling conformational study of N-benzyl, N-n-propyl (2-methyl-3-nitrophenyl)acetamide

    International Nuclear Information System (INIS)

    Nicolle, E.; Benoit-Guyod, M.; Namil, A.; Cussac, M.; Leclerc, G.; Maldivi, P.

    1995-01-01

    The conformation of N-benzyl-N-n-propyl (2-methyl-3-nitrophenyl) acetamide 1 in dimethyl sulfoxide (DMSO-d 6 ) or chloroform (CDCL 3 ) solution was studied using 1 H and 13 CNMR analysis. In solution, 1 existed as two distinct Z and E isomers, which could not be separated at laboratory temperature. Both conformations were in equivalent proportions in chloroform whereas in a polar solvent (DMSO), the conformation Z was more usual with the aromatic rings in a transposition. Major and minor rotation isomers were assigned form the '1H and 13 C NMR chemical shifts determined at 293 K. Separate treatment of signals displayed by two different methylene groups gave comparable activation parameters (ΔG ∼ 16 kcal/mol). Conformational analysis and measurement of the rotational barrier between the E and Z conformers by molecular modeling (Sybyl program) were performed. (authors). 14 refs., 8 figs

  18. Multichannel conformal blocks for scattering amplitudes

    Science.gov (United States)

    Belitsky, A. V.

    2018-05-01

    By performing resummation of small fermion-antifermion pairs within the pentagon form factor program to scattering amplitudes in planar N = 4 superYang-Mills theory, we construct multichannel conformal blocks within the flux-tube picture for N-sided NMHV polygons. This procedure is equivalent to summation of descendants of conformal primaries in the OPE framework. The resulting conformal partial waves are determined by multivariable hypergeometric series of Lauricella-Saran type.

  19. Conformal hyperbolicity of Lorentzian warped products

    International Nuclear Information System (INIS)

    Markowitz, M.J.

    1982-01-01

    A space-time M is said to be conformally hyperbolic if the intrinsic conformal Lorentz pseudodistance dsub(M) is a true distance. In this paper criteria are derived which insure the conformal hyperbolicity of certain space-times which are generalizations of the Robertson-Walker spaces. Then dsub(M) is determined explicitly for Einstein-de Sitter space, and important cosmological model. (author)

  20. Conformal hyperbolicity of Lorentzian warped products

    Energy Technology Data Exchange (ETDEWEB)

    Markowitz, M.J. (Chicago Univ., IL (USA). Dept. of Mathematics)

    1982-12-01

    A space-time M is said to be conformally hyperbolic if the intrinsic conformal Lorentz pseudodistance dsub(M) is a true distance. In this paper criteria are derived which insure the conformal hyperbolicity of certain space-times which are generalizations of the Robertson-Walker spaces. Then dsub(M) is determined explicitly for Einstein-de Sitter space, and important cosmological model.

  1. Viscous conformal gauge theories

    DEFF Research Database (Denmark)

    Toniato, Arianna; Sannino, Francesco; Rischke, Dirk H.

    2017-01-01

    We present the conformal behavior of the shear viscosity-to-entropy density ratio and the fermion-number diffusion coefficient within the perturbative regime of the conformal window for gauge-fermion theories.......We present the conformal behavior of the shear viscosity-to-entropy density ratio and the fermion-number diffusion coefficient within the perturbative regime of the conformal window for gauge-fermion theories....

  2. Conformal Einstein spaces

    International Nuclear Information System (INIS)

    Kozameh, C.N.; Newman, E.T.; Tod, K.P.

    1985-01-01

    Conformal transformations in four-dimensional. In particular, a new set of two necessary and sufficient conditions for a space to be conformal to an Einstein space is presented. The first condition defines the class of spaces conformal to C spaces, whereas the last one (the vanishing of the Bach tensor) gives the particular subclass of C spaces which are conformally related to Einstein spaces. (author)

  3. Overview of frequency bandwidth determination techniques of useful signal in case of leaks detection by correlation method

    International Nuclear Information System (INIS)

    Faerman, V A; Avramchuk, V S; Luneva, E E

    2014-01-01

    In this paper an overview of useful signal detection methods on the background of intense noise and limits determination methods of useful signal is presented. The following features are considered: peculiarities of usage of correlation analysis, cross-amplitude spectrum, coherence function, cross-phase spectrum, time-frequency correlation function in case of frequency limits determination as well as leaks detection in pipelines. The possibility of using time-frequency correlation function for solving above named issues is described. Time- frequency correlation function provides information about the signals correlation for each of the investigated frequency bands. Data about location of peaks on the surface plot of a time- frequency correlation function allows making an assumption about the spectral composition of useful signal and its frequency boundaries

  4. Superspace conformal field theory

    Energy Technology Data Exchange (ETDEWEB)

    Quella, Thomas [Koeln Univ. (Germany). Inst. fuer Theoretische Physik; Schomerus, Volker [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)

    2013-07-15

    Conformal sigma models and WZW models on coset superspaces provide important examples of logarithmic conformal field theories. They possess many applications to problems in string and condensed matter theory. We review recent results and developments, including the general construction of WZW models on type I supergroups, the classification of conformal sigma models and their embedding into string theory.

  5. Superspace conformal field theory

    International Nuclear Information System (INIS)

    Quella, Thomas

    2013-07-01

    Conformal sigma models and WZW models on coset superspaces provide important examples of logarithmic conformal field theories. They possess many applications to problems in string and condensed matter theory. We review recent results and developments, including the general construction of WZW models on type I supergroups, the classification of conformal sigma models and their embedding into string theory.

  6. Determination of the wavelength dependence of the differential pathlength factor from near-infrared pulse signals

    Science.gov (United States)

    Kohl, Matthias; Nolte, Christian; Heekeren, Hauke R.; Horst, Susanne; Scholz, Udo; Obrig, Hellmuth; Villringer, Arno

    1998-06-01

    For the calculation of changes in oxyhaemoglobin, deoxyhaemoglobin and the redox state of cytochrome-c-oxidase from attenuation data via a modified Beer-Lambert equation the wavelength dependence of the differential pathlength factor (DPF) has to be taken into account. The DPF, i.e. the ratio of the mean optical pathlength and the physical light source-detector separation at each wavelength, determines the crosstalk between the different concentrations and is therefore essential for a sensitive detection of chromophore changes. Here a simple method is suggested to estimate the wavelength dependence of the DPF from pulse-induced attenuation changes measured on the head of adult humans. The essence is that the DPF is the ratio of the attenuation changes over absorption coefficient changes, and that the spectral form of the pulse correlated absorption coefficient change can be assumed to be proportional to the extinction coefficient of blood. Indicators for the validity of the DPF derived for wavelengths between 700 and 970 nm are the stability of the calculated haemoglobin and cytochrome signals with variations of the wavelength range included for their calculation and its overall agreement with the data available from the literature.

  7. Analyzing surface EMG signals to determine relationship between jaw imbalance and arm strength loss

    Directory of Open Access Journals (Sweden)

    Truong Quang Dang Khoa

    2012-08-01

    Full Text Available Abstract Background This study investigated the relationship between dental occlusion and arm strength; in particular, the imbalance in the jaw can cause loss in arm strength phenomenon. One of the goals of this study was to record the maximum forces that the subjects can resist against the pull-down force on their hands while biting a spacer of adjustable height on the right or left side of the jaw. Then EMG measurement was used to determine the EMG-Force relationship of the jaw, neck and arms muscles. This gave us useful insights on the arms strength loss due to the biomechanical effects of the imbalance in the jaw mechanism. Methods In this study to determine the effects of the imbalance in the jaw to the strength of the arms, we conducted experiments with a pool of 20 healthy subjects of both genders. The subjects were asked to resist a pull down force applied on the contralateral arm while biting on a firm spacer using one side of the jaw. Four different muscles – masseter muscles, deltoid muscles, bicep muscles and trapezoid muscles – were involved. Integrated EMG (iEMG and Higuchi fractal dimension (HFD were used to analyze the EMG signals. Results The results showed that (1 Imbalance in the jaw causes loss of arm strength contra-laterally; (2 The loss is approximately a linear function of the height of the spacers. Moreover, the iEMG showed the intensity of muscle activities decreased when the degrees of jaw imbalance increased (spacer thickness increased. In addition, the tendency of Higuchi fractal dimension decreased for all muscles. Conclusions This finding indicates that muscle fatigue and the decrease in muscle contraction level leads to the loss of arm strength.

  8. Quantum Conformal Algebras and Closed Conformal Field Theory

    CERN Document Server

    Anselmi, D

    1999-01-01

    We investigate the quantum conformal algebras of N=2 and N=1 supersymmetric gauge theories. Phenomena occurring at strong coupling are analysed using the Nachtmann theorem and very general, model-independent, arguments. The results lead us to introduce a novel class of conformal field theories, identified by a closed quantum conformal algebra. We conjecture that they are the exact solution to the strongly coupled large-N_c limit of the open conformal field theories. We study the basic properties of closed conformal field theory and work out the operator product expansion of the conserved current multiplet T. The OPE structure is uniquely determined by two central charges, c and a. The multiplet T does not contain just the stress-tensor, but also R-currents and finite mass operators. For this reason, the ratio c/a is different from 1. On the other hand, an open algebra contains an infinite tower of non-conserved currents, organized in pairs and singlets with respect to renormalization mixing. T mixes with a se...

  9. Anomalous Dimensions of Conformal Baryons

    DEFF Research Database (Denmark)

    Pica, Claudio; Sannino, Francesco

    2016-01-01

    We determine the anomalous dimensions of baryon operators for the three color theory as function of the number of massless flavours within the conformal window to the maximum known order in perturbation theory. We show that the anomalous dimension of the baryon is controllably small, within...

  10. Net Analyte Signal Standard Additions Method for Simultaneous Determination of Sulfamethoxazole and Trimethoprim in Pharmaceutical Formulations and Biological Fluids

    Directory of Open Access Journals (Sweden)

    M. H. Givianrad

    2012-01-01

    Full Text Available The applicability of a novel net analyte signal standard addition method (NASSAM to the resolving of overlapping spectra corresponding to the sulfamethoxazole and trimethoprim was verified by UV-visible spectrophotometry. The results confirmed that the net analyte signal standard additions method with simultaneous addition of both analytes is suitable for the simultaneous determination of sulfamethoxazole and trimethoprim in aqueous media. Moreover, applying the net analyte signal standard additions method revealed that the two drugs could be determined simultaneously with the concentration ratios of sulfamethoxazole to trimethoprim varying from 1:35 to 60:1 in the mixed samples. In addition, the limits of detections were 0.26 and 0.23 μmol L-1 for sulfamethoxazole and trimethoprim, respectively. The proposed method has been effectively applied to the simultaneous determination of sulfamethoxazole and trimethoprim in some synthetic, pharmaceutical formulation and biological fluid samples.

  11. Non-conformable, partial and conformable transposition

    DEFF Research Database (Denmark)

    König, Thomas; Mäder, Lars Kai

    2013-01-01

    and the Commission regarding a directive’s outcome, play a much more strategic role than has to date acknowledged in the transposition literature. Whereas disagreement of a member state delays conformable transposition, it speeds up non-conformable transposition. Disagreement of the Commission only prolongs...... the transposition process. We therefore conclude that a stronger focus on an effective sanctioning mechanism is warranted for safeguarding compliance with directives....

  12. PAK4 crystal structures suggest unusual kinase conformational movements.

    Science.gov (United States)

    Zhang, Eric Y; Ha, Byung Hak; Boggon, Titus J

    2018-02-01

    In order for protein kinases to exchange nucleotide they must open and close their catalytic cleft. These motions are associated with rotations of the N-lobe, predominantly around the 'hinge region'. We conducted an analysis of 28 crystal structures of the serine-threonine kinase, p21-activated kinase 4 (PAK4), including three newly determined structures in complex with staurosporine, FRAX486, and fasudil (HA-1077). We find an unusual motion between the N-lobe and C-lobe of PAK4 that manifests as a partial unwinding of helix αC. Principal component analysis of the crystal structures rationalizes these movements into three major states, and analysis of the kinase hydrophobic spines indicates concerted movements that create an accessible back pocket cavity. The conformational changes that we observe for PAK4 differ from previous descriptions of kinase motions, and although we observe these differences in crystal structures there is the possibility that the movements observed may suggest a diversity of kinase conformational changes associated with regulation. Protein kinases are key signaling proteins, and are important drug targets, therefore understanding their regulation is important for both basic research and clinical points of view. In this study, we observe unusual conformational 'hinging' for protein kinases. Hinging, the opening and closing of the kinase sub-domains to allow nucleotide binding and release, is critical for proper kinase regulation and for targeted drug discovery. We determine new crystal structures of PAK4, an important Rho-effector kinase, and conduct analyses of these and previously determined structures. We find that PAK4 crystal structures can be classified into specific conformational groups, and that these groups are associated with previously unobserved hinging motions and an unusual conformation for the kinase hydrophobic core. Our findings therefore indicate that there may be a diversity of kinase hinging motions, and that these may

  13. Electrophysiological precursors of social conformity

    Science.gov (United States)

    Rieskamp, Jörg; Tugin, Sergey; Ossadtchi, Alexey; Krutitskaya, Janina; Klucharev, Vasily

    2013-01-01

    Humans often change their beliefs or behavior due to the behavior or opinions of others. This study explored, with the use of human event-related potentials (ERPs), whether social conformity is based on a general performance-monitoring mechanism. We tested the hypothesis that conflicts with a normative group opinion evoke a feedback-related negativity (FRN) often associated with performance monitoring and subsequent adjustment of behavior. The experimental results show that individual judgments of facial attractiveness were adjusted in line with a normative group opinion. A mismatch between individual and group opinions triggered a frontocentral negative deflection with the maximum at 200 ms, similar to FRN. Overall, a conflict with a normative group opinion triggered a cascade of neuronal responses: from an earlier FRN response reflecting a conflict with the normative opinion to a later ERP component (peaking at 380 ms) reflecting a conforming behavioral adjustment. These results add to the growing literature on neuronal mechanisms of social influence by disentangling the conflict-monitoring signal in response to the perceived violation of social norms and the neural signal of a conforming behavioral adjustment. PMID:22683703

  14. Analysis of calcium-induced conformational changes in calcium-binding allergens and quantitative determination of their IgE binding properties.

    Science.gov (United States)

    Parody, Nuria; Fuertes, Miguel Angel; Alonso, Carlos; Pico de Coaña, Yago

    2013-01-01

    The polcalcin family is one of the most epidemiologically relevant families of calcium-binding allergens. Polcalcins are potent plant allergens that contain one or several EF-hand motifs and their allergenicity is primarily associated with the Ca(2+)-bound form of the protein. Conformation, stability, as well as IgE recognition of calcium-binding allergens greatly depend on the presence of protein-bound calcium ions. We describe a protocol that uses three techniques (SDS-PAGE, circular dichroism spectroscopy, and ELISA) to describe the effects that calcium has on the structural changes in an allergen and its IgE binding properties.

  15. Instantons in conformal gravity

    International Nuclear Information System (INIS)

    Strominger, A.; Horowitz, G.T.; Perry, M.J.

    1984-01-01

    Fe study extrema of the general conformally invariant action: Ssub(c)=∫1/sub(α) 2 Csup(abcd)Csub(abcd)+γRsup(abcd*)Rsup(*)sub(abcd)+iTHETARsup(abcd)*Rsub(abcd). We find the first examples in four dimensions of asymptotically euclidean gravitational instantons. These have arbitrary Euler number and Hirzebruch signature. Some of these instantons represent tunneling between zero-curvature vacua that are not related by small gauge transformations. Others represent tunneling between flat space and topologically non-trivial zero-energy initial data. A general formula for the one-loop determinant is derived in terms of the renormalization group invariant masses, the volume of space-time, the Euler number and the Hirzebruch signature. (orig.)

  16. Intra-Tumour Signalling Entropy Determines Clinical Outcome in Breast and Lung Cancer

    Science.gov (United States)

    Banerji, Christopher R. S.; Severini, Simone; Caldas, Carlos; Teschendorff, Andrew E.

    2015-01-01

    The cancer stem cell hypothesis, that a small population of tumour cells are responsible for tumorigenesis and cancer progression, is becoming widely accepted and recent evidence has suggested a prognostic and predictive role for such cells. Intra-tumour heterogeneity, the diversity of the cancer cell population within the tumour of an individual patient, is related to cancer stem cells and is also considered a potential prognostic indicator in oncology. The measurement of cancer stem cell abundance and intra-tumour heterogeneity in a clinically relevant manner however, currently presents a challenge. Here we propose signalling entropy, a measure of signalling pathway promiscuity derived from a sample’s genome-wide gene expression profile, as an estimate of the stemness of a tumour sample. By considering over 500 mixtures of diverse cellular expression profiles, we reveal that signalling entropy also associates with intra-tumour heterogeneity. By analysing 3668 breast cancer and 1692 lung adenocarcinoma samples, we further demonstrate that signalling entropy correlates negatively with survival, outperforming leading clinical gene expression based prognostic tools. Signalling entropy is found to be a general prognostic measure, valid in different breast cancer clinical subgroups, as well as within stage I lung adenocarcinoma. We find that its prognostic power is driven by genes involved in cancer stem cells and treatment resistance. In summary, by approximating both stemness and intra-tumour heterogeneity, signalling entropy provides a powerful prognostic measure across different epithelial cancers. PMID:25793737

  17. Intra-tumour signalling entropy determines clinical outcome in breast and lung cancer.

    Directory of Open Access Journals (Sweden)

    Christopher R S Banerji

    2015-03-01

    Full Text Available The cancer stem cell hypothesis, that a small population of tumour cells are responsible for tumorigenesis and cancer progression, is becoming widely accepted and recent evidence has suggested a prognostic and predictive role for such cells. Intra-tumour heterogeneity, the diversity of the cancer cell population within the tumour of an individual patient, is related to cancer stem cells and is also considered a potential prognostic indicator in oncology. The measurement of cancer stem cell abundance and intra-tumour heterogeneity in a clinically relevant manner however, currently presents a challenge. Here we propose signalling entropy, a measure of signalling pathway promiscuity derived from a sample's genome-wide gene expression profile, as an estimate of the stemness of a tumour sample. By considering over 500 mixtures of diverse cellular expression profiles, we reveal that signalling entropy also associates with intra-tumour heterogeneity. By analysing 3668 breast cancer and 1692 lung adenocarcinoma samples, we further demonstrate that signalling entropy correlates negatively with survival, outperforming leading clinical gene expression based prognostic tools. Signalling entropy is found to be a general prognostic measure, valid in different breast cancer clinical subgroups, as well as within stage I lung adenocarcinoma. We find that its prognostic power is driven by genes involved in cancer stem cells and treatment resistance. In summary, by approximating both stemness and intra-tumour heterogeneity, signalling entropy provides a powerful prognostic measure across different epithelial cancers.

  18. Investigation of conformal and intensity-modulated radiation therapy techniques to determine the absorbed fetal dose in pregnant patients with breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Öğretici, Akın, E-mail: akinogretici@gmail.com; Akbaş, Uğur; Köksal, Canan; Bilge, Hatice

    2016-07-01

    The aim of this research was to investigate the fetal doses of pregnant patients undergoing conformal radiotherapy or intensity-modulated radiation therapy (IMRT) for breast cancers. An Alderson Rando phantom was chosen to simulate a pregnant patient with breast cancer who is receiving radiation therapy. This phantom was irradiated using the Varian Clinac DBX 600 system (Varian Medical System, Palo Alto, CA) linear accelerator, according to the standard treatment plans of both three-dimensional conformal radiation therapy (3-D CRT) and IMRT techniques. Thermoluminescent dosimeters were used to measure the irradiated phantom's virtually designated uterus area. Thermoluminescent dosimeter measurements (in the phantom) revealed that the mean cumulative fetal dose for 3-D CRT is 1.39 cGy and for IMRT it is 8.48 cGy, for a pregnant breast cancer woman who received radiation treatment of 50 Gy. The fetal dose was confirmed to increase by 70% for 3-D CRT and 40% for IMRT, if it is closer to the irradiated field by 5 cm. The mean fetal dose from 3-D CRT is 1.39 cGy and IMRT is 8.48 cGy, consistent with theoretic calculations. The IMRT technique causes the fetal dose to be 5 times more than that of 3-D CRT. Theoretic knowledge concerning the increase in the peripheral doses as the measurements approached the beam was also practically proven.

  19. Determinants of cell-to-cell variability in protein kinase signaling.

    Science.gov (United States)

    Jeschke, Matthias; Baumgärtner, Stephan; Legewie, Stefan

    2013-01-01

    Cells reliably sense environmental changes despite internal and external fluctuations, but the mechanisms underlying robustness remain unclear. We analyzed how fluctuations in signaling protein concentrations give rise to cell-to-cell variability in protein kinase signaling using analytical theory and numerical simulations. We characterized the dose-response behavior of signaling cascades by calculating the stimulus level at which a pathway responds ('pathway sensitivity') and the maximal activation level upon strong stimulation. Minimal kinase cascades with gradual dose-response behavior show strong variability, because the pathway sensitivity and the maximal activation level cannot be simultaneously invariant. Negative feedback regulation resolves this trade-off and coordinately reduces fluctuations in the pathway sensitivity and maximal activation. Feedbacks acting at different levels in the cascade control different aspects of the dose-response curve, thereby synergistically reducing the variability. We also investigated more complex, ultrasensitive signaling cascades capable of switch-like decision making, and found that these can be inherently robust to protein concentration fluctuations. We describe how the cell-to-cell variability of ultrasensitive signaling systems can be actively regulated, e.g., by altering the expression of phosphatase(s) or by feedback/feedforward loops. Our calculations reveal that slow transcriptional negative feedback loops allow for variability suppression while maintaining switch-like decision making. Taken together, we describe design principles of signaling cascades that promote robustness. Our results may explain why certain signaling cascades like the yeast pheromone pathway show switch-like decision making with little cell-to-cell variability.

  20. Determinants of cell-to-cell variability in protein kinase signaling.

    Directory of Open Access Journals (Sweden)

    Matthias Jeschke

    Full Text Available Cells reliably sense environmental changes despite internal and external fluctuations, but the mechanisms underlying robustness remain unclear. We analyzed how fluctuations in signaling protein concentrations give rise to cell-to-cell variability in protein kinase signaling using analytical theory and numerical simulations. We characterized the dose-response behavior of signaling cascades by calculating the stimulus level at which a pathway responds ('pathway sensitivity' and the maximal activation level upon strong stimulation. Minimal kinase cascades with gradual dose-response behavior show strong variability, because the pathway sensitivity and the maximal activation level cannot be simultaneously invariant. Negative feedback regulation resolves this trade-off and coordinately reduces fluctuations in the pathway sensitivity and maximal activation. Feedbacks acting at different levels in the cascade control different aspects of the dose-response curve, thereby synergistically reducing the variability. We also investigated more complex, ultrasensitive signaling cascades capable of switch-like decision making, and found that these can be inherently robust to protein concentration fluctuations. We describe how the cell-to-cell variability of ultrasensitive signaling systems can be actively regulated, e.g., by altering the expression of phosphatase(s or by feedback/feedforward loops. Our calculations reveal that slow transcriptional negative feedback loops allow for variability suppression while maintaining switch-like decision making. Taken together, we describe design principles of signaling cascades that promote robustness. Our results may explain why certain signaling cascades like the yeast pheromone pathway show switch-like decision making with little cell-to-cell variability.

  1. LIF-activated Jak signaling determines Esrrb expression during late-stage reprogramming

    Directory of Open Access Journals (Sweden)

    Delun Huang

    2018-01-01

    Full Text Available The regulatory process of naïve-state induced pluripotent stem cell (iPSC generation is not well understood. Leukemia inhibitory factor (LIF-activated Janus kinase/signal transducer and activator of transcription 3 (Jak/Stat3 is the master regulator for naïve-state pluripotency achievement and maintenance. The estrogen-related receptor beta (Esrrb serves as a naïve-state marker gene regulating self-renewal of embryonic stem cells (ESCs. However, the interconnection between Esrrb and LIF signaling for pluripotency establishment in reprogramming is unclear. We screened the marker genes critical for complete reprogramming during mouse iPSC generation, and identified genes including Esrrb that are responsive to LIF/Jak pathway signaling. Overexpression of Esrrb resumes the reprogramming halted by inhibition of Jak activity in partially reprogrammed cells (pre-iPSCs, and leads to the generation of pluripotent iPSCs. We further show that neither overexpression of Nanog nor stimulation of Wnt signaling, two upstream regulators of Esrrb in ESCs, stimulates the expression of Esrrb in reprogramming when LIF or Jak activity is blocked. Our study demonstrates that Esrrb is a specific reprogramming factor regulated downstream of the LIF/Jak signaling pathway. These results shed new light on the regulatory role of LIF pathway on complete pluripotency establishment during iPSC generation.

  2. Conformal Killing vectors in Robertson-Walker spacetimes

    International Nuclear Information System (INIS)

    Maartens, R.; Maharaj, S.d.

    1986-01-01

    It is well known that Robertson-Walker spacetimes admit a conformal Killingl vector normal to the spacelike homogeneous hypersurfaces. Because these spacetimes are conformally flat, there are a further eight conformal Killing vectors, which are neither normal nor tangent to the homogeneous hypersurfaces. The authors find these further conformal Killing vectors and the Lie algebra of the full G 15 of conformal motions. Conditions on the metric scale factor are determined which reduce some of the conformal Killing vectors to homothetic Killing vectors or Killing vectors, allowing one to regain in a unified way the known special geometries. The non-normal conformal Killing vectors provide a counter-example to show that conformal motions do not, in general, map a fluid flow conformally. These non-normal vectors are also used to find the general solution of the null geodesic equation and photon Liouville equation. (author)

  3. Equivalent dose determination in foraminifera: analytical description of the CO2--signal dose-response curve

    International Nuclear Information System (INIS)

    Hoffmann, D.; Woda, C.; Mangini, A.

    2003-01-01

    The dose-response of the CO 2 - signal (g=2.0006) in foraminifera with ages between 19 and 300 ka is investigated. The sum of two exponential saturation functions is an adequate function to describe the dose-response curve up to an additional dose of 8000 Gy. It yields excellent dating results but requires an artificial doses of at least 5000 Gy. For small additional doses of about 500 Gy the single exponential saturation function can be used to calculate a reliable equivalent dose D E , although it does not describ the dose-response for higher doses. The CO 2 - -signal dose-response indicates that the signal has two components of which one is less stable than the other

  4. Conformal Aspects of QCD

    Energy Technology Data Exchange (ETDEWEB)

    Brodsky, S

    2003-11-19

    Theoretical and phenomenological evidence is now accumulating that the QCD coupling becomes constant at small virtuality; i.e., {alpha}{sub s}(Q{sup 2}) develops an infrared fixed point in contradiction to the usual assumption of singular growth in the infrared. For example, the hadronic decays of the {tau} lepton can be used to determine the effective charge {alpha}{sub {tau}}(m{sub {tau}{prime}}{sup 2}) for a hypothetical {tau}-lepton with mass in the range 0 < m{sub {tau}{prime}} < m{sub {tau}}. The {tau} decay data at low mass scales indicates that the effective charge freezes at a value of s = m{sub {tau}{prime}}{sup 2} of order 1 GeV{sup 2} with a magnitude {alpha}{sub {tau}} {approx} 0.9 {+-} 0.1. The near-constant behavior of effective couplings suggests that QCD can be approximated as a conformal theory even at relatively small momentum transfer and why there are no significant running coupling corrections to quark counting rules for exclusive processes. The AdS/CFT correspondence of large N{sub c} supergravity theory in higher-dimensional anti-de Sitter space with supersymmetric QCD in 4-dimensional space-time also has interesting implications for hadron phenomenology in the conformal limit, including an all-orders demonstration of counting rules for exclusive processes and light-front wavefunctions. The utility of light-front quantization and light-front Fock wavefunctions for analyzing nonperturbative QCD and representing the dynamics of QCD bound states is also discussed.

  5. Determination of Lineaments of the Sea of Marmara using Normalized Derivatives and Analytic Signals

    International Nuclear Information System (INIS)

    Oruc, B.

    2007-01-01

    The normalized derivatives and analytic signals calculated from magnetic anomaly map present useful results for the structural interpretation. The effectiveness of the methods on the solutions of lineaments has been tested for the edges of the thin-plate model. In the field data, magnetic anomaly map observed in the middle section of Marmara Sea has been used. The approximate solutions have been obtained for the lineaments of the area related in North Anatolia Fault from the characteristic images of the normalized derivatives and horizontal derivative analytic signals

  6. The Role of Retinal Determination Gene Network (RDGN) in Hormone Signaling Transduction and Prostate Tumorigenesis

    Science.gov (United States)

    2012-10-01

    PI3K/ Akt and MAPK/Erk signaling. We identified the A-type cyclin, cyclin A1 as an important downstream target of PI3K/ Akt (59); 3) autocrine IL-6...DACH1 inhibits transforming growth factor-beta signaling through binding Smad4 . J Biol Chem. 2003; 278(51):51673- 84. 33. Le Grand F, Grifone R, Mourikis...androgen receptor. Endocr Relat Cancer. 2009; 16(1):155-69. 59. Wegiel B, Bjartell A, Culig Z, Persson JL. Interleukin-6 activates PI3K/ Akt pathway

  7. Conformational analysis of the Sda determinant-containing tetrasaccharide and two mimics in aqueous solution by using 1H NMR ROESY spectroscopy in combination with MD simulations

    International Nuclear Information System (INIS)

    Blanco, Jose L. Jimenez; Rooijen, Johannes J.M. van; Erbel, Paul J.A.; Leeflang, Bas R.; Kamerling, Johannis P.; Vliegenthart, Johannes F.G.

    2000-01-01

    The conformational behaviour of the spacer-linked synthetic Sd a tetrasaccharide β-d-GalpNAc-(1 → 4)-[α-Neu5Ac-(2 → 3)]-β-d-Galp-(1 → 4)-β-d-GlcpNAc-(1 → O) (CH 2 ) 5 NH 2 (1) and the two mimics β-d-Galp-(1 → 4)-[α-Neu5Ac-(2 → 3)]-β-d-Galp-(1 → 4)-β-d-GlcpNAc-(1 → O)(CH 2 ) 5 NH 2 (2) and β-d-GlcpNAc-(1 → 4)-[α-Neu5Ac-(2 → 3)]-β-d-Galp-(1 → 4)-β-d-GlcpNAc-(1 → O) (CH 2 ) 5 NH 2 (3) were investigated by 1 H NMR spectroscopy in combination with molecular dynamics (MD) simulations in water. Experimental 2D 1 H ROESY cross-peak intensities (ROEs) of the tetrasaccharides were compared with calculated ROEs derived from MD trajectories using the CROSREL program. Analysis of these data indicated that the oligosaccharidic skeletons of the compounds 1-3 are rather rigid, especially the β-d-Hex(NAc)-(1 → 4)-[α-Neu5Ac-(2 → 3)]-β-d-Galp fragments. The α- Neu5-Ac-(2 → 3)-β-d-Galp linkage occurred in two different energy minima in the three-dimensional structure of the compounds 1-3 in aqueous solution. Experimental data and dynamics simulations supported the finding that the higher energy rotamer (CHEAT forcefield) was abundant in compounds 1 and 3 due to the existence of a hydrogen bond between the carboxyl group of the sialic acid and the acetamido group of the terminal monosaccharide (GalNAc or GlcNAc) unit. The conformational similarity between 1 and 3 leads to the suggestion that also their activities will be alike.

  8. Conformal anomalies in curved space--time

    Energy Technology Data Exchange (ETDEWEB)

    Duncan, A.

    1976-11-01

    The general form of the conformal anomaly in a dimensionally regularized theory of massless fermions in a background metric is shown to be determined by the first few terms of weak field perturbation theory.

  9. A Novel, Low-Cost Conformable Lander

    Data.gov (United States)

    National Aeronautics and Space Administration — The primary focus of this activity will be to outline a preliminary mechanical design for this conforming lander. Salient issues to be worked include (1) determining...

  10. Cytoplasmic organelles determine complexity and specificity of calcium signalling in adrenal chromaffin cells

    Czech Academy of Sciences Publication Activity Database

    Garsia-Sancho, J.; Verkhratsky, Alexei

    2008-01-01

    Roč. 192, č. 2 (2008), s. 263-271 ISSN 1748-1708 Institutional research plan: CEZ:AV0Z50390512 Keywords : Ca2+ signalling * calcium microdomains * chromaffin cells Subject RIV: JE - Non-nuclear Energetics, Energy Consumption ; Use Impact factor: 2.455, year: 2008

  11. Biochar and microbial signaling: production conditions determine effects on microbial communication

    Science.gov (United States)

    Masiello, Caroline A.; Chen, Ye; Gao, Xiaodong; Liu, Shirley; Cheng, Hsiao-Ying; Bennett, Matthew R.; Rudgers, Jennifer A.; Wagner, Daniel S.; Zygourakis, Kyriacos; Silberg, Jonathan J.

    2013-01-01

    Charcoal has a long soil residence time, which has resulted in its production and use as a carbon sequestration technique (biochar). A range of biological effects can be triggered by soil biochar that can positively and negatively influence carbon storage, such as changing the decomposition rate of organic matter and altering plant biomass production. Sorption of cellular signals has been hypothesized to underlie some of these effects, but it remains unknown whether the binding of biochemical signals occurs, and if so, on time scales relevant to microbial growth and communication. We examined biochar sorption of N-3-oxo-dodecanoyl-L-homoserine lactone, an acyl-homoserine lactone (AHL) intercellular signaling molecule used by many gram-negative soil microbes to regulate gene expression. We show that wood biochars disrupt communication within a growing multicellular system that is made up of sender cells that synthesize AHL and receiver cells that express green fluorescent protein in response to an AHL signal. However, biochar inhibition of AHL-mediated cell-cell communication varied, with the biochar prepared at 700°C (surface area of 301 m2/g) inhibiting cellular communication 10-fold more than an equivalent mass of biochar prepared at 300°C (surface area of 3 m2/g). These findings provide the first direct evidence that biochars elicit a range of effects on gene expression dependent on intercellular signaling, implicating the method of biochar preparation as a parameter that could be tuned to regulate microbial-dependent soil processes, like nitrogen fixation and pest attack of root crops. PMID:24066613

  12. Biochar and microbial signaling: production conditions determine effects on microbial communication.

    Science.gov (United States)

    Masiello, Caroline A; Chen, Ye; Gao, Xiaodong; Liu, Shirley; Cheng, Hsiao-Ying; Bennett, Matthew R; Rudgers, Jennifer A; Wagner, Daniel S; Zygourakis, Kyriacos; Silberg, Jonathan J

    2013-10-15

    Charcoal has a long soil residence time, which has resulted in its production and use as a carbon sequestration technique (biochar). A range of biological effects can be triggered by soil biochar that can positively and negatively influence carbon storage, such as changing the decomposition rate of organic matter and altering plant biomass production. Sorption of cellular signals has been hypothesized to underlie some of these effects, but it remains unknown whether the binding of biochemical signals occurs, and if so, on time scales relevant to microbial growth and communication. We examined biochar sorption of N-3-oxo-dodecanoyl-L-homoserine lactone, an acyl-homoserine lactone (AHL) intercellular signaling molecule used by many gram-negative soil microbes to regulate gene expression. We show that wood biochars disrupt communication within a growing multicellular system that is made up of sender cells that synthesize AHL and receiver cells that express green fluorescent protein in response to an AHL signal. However, biochar inhibition of AHL-mediated cell-cell communication varied, with the biochar prepared at 700 °C (surface area of 301 m(2)/g) inhibiting cellular communication 10-fold more than an equivalent mass of biochar prepared at 300 °C (surface area of 3 m(2)/g). These findings provide the first direct evidence that biochars elicit a range of effects on gene expression dependent on intercellular signaling, implicating the method of biochar preparation as a parameter that could be tuned to regulate microbial-dependent soil processes, like nitrogen fixation and pest attack of root crops.

  13. Induced quantum conformal gravity

    International Nuclear Information System (INIS)

    Novozhilov, Y.V.; Vassilevich, D.V.

    1988-11-01

    Quantum gravity is considered as induced by matter degrees of freedom and related to the symmetry breakdown in the low energy region of a non-Abelian gauge theory of fundamental fields. An effective action for quantum conformal gravity is derived where both the gravitational constant and conformal kinetic term are positive. Relation with induced classical gravity is established. (author). 15 refs

  14. Thickenings and conformal gravity

    Science.gov (United States)

    Lebrun, Claude

    1991-07-01

    A twistor correspondence is given for complex conformal space-times with vanishing Bach and Eastwood-Dighton tensors; when the Weyl curvature is algebraically general, these equations are precisely the conformal version of Einstein's vacuum equations with cosmological constant. This gives a fully curved version of the linearized correspondence of Baston and Mason [B-M].

  15. Thickenings and conformal gravity

    Energy Technology Data Exchange (ETDEWEB)

    LeBrun, C. (State Univ. of New York, Stony Brook, NY (USA). Dept. of Mathematics)

    1991-07-01

    A twistor correspondence is given for complex conformal space-times with vanishing Bach and Eastwood-Dighton tensors; when the Weyl curvature is algebraically general, these equations are precisely the conformal version of Einstein's vacuum equations with cosmological constant. This gives a fully curved version of the linearized correspondence of Baston and Mason (B-M). (orig.).

  16. Thickenings and conformal gravity

    International Nuclear Information System (INIS)

    LeBrun, C.

    1991-01-01

    A twistor correspondence is given for complex conformal space-times with vanishing Bach and Eastwood-Dighton tensors; when the Weyl curvature is algebraically general, these equations are precisely the conformal version of Einstein's vacuum equations with cosmological constant. This gives a fully curved version of the linearized correspondence of Baston and Mason [B-M]. (orig.)

  17. Conformal transformations in superspace

    International Nuclear Information System (INIS)

    Dao Vong Duc

    1977-01-01

    The spinor extension of the conformal algebra is investigated. The transformation law of superfields under the conformal coordinate inversion R defined in the superspace is derived. Using R-technique, the superconformally covariant two-point and three-point correlation functions are found

  18. Conformational stability of calreticulin

    DEFF Research Database (Denmark)

    Jørgensen, C.S.; Trandum, C.; Larsen, N.

    2005-01-01

    The conformational stability of calreticulin was investigated. Apparent unfolding temperatures (T-m) increased from 31 degrees C at pH 5 to 51 degrees C at pH 9, but electrophoretic analysis revealed that calreticulin oligomerized instead of unfolding. Structural analyses showed that the single C......-terminal a-helix was of major importance to the conformational stability of calreticulin....

  19. Defects in conformal field theory

    International Nuclear Information System (INIS)

    Billò, Marco; Gonçalves, Vasco; Lauria, Edoardo; Meineri, Marco

    2016-01-01

    We discuss consequences of the breaking of conformal symmetry by a flat or spherical extended operator. We adapt the embedding formalism to the study of correlation functions of symmetric traceless tensors in the presence of the defect. Two-point functions of a bulk and a defect primary are fixed by conformal invariance up to a set of OPE coefficients, and we identify the allowed tensor structures. A correlator of two bulk primaries depends on two cross-ratios, and we study its conformal block decomposition in the case of external scalars. The Casimir equation in the defect channel reduces to a hypergeometric equation, while the bulk channel blocks are recursively determined in the light-cone limit. In the special case of a defect of codimension two, we map the Casimir equation in the bulk channel to the one of a four-point function without defect. Finally, we analyze the contact terms of the stress-tensor with the extended operator, and we deduce constraints on the CFT data. In two dimensions, we relate the displacement operator, which appears among the contact terms, to the reflection coefficient of a conformal interface, and we find unitarity bounds for the latter.

  20. Defects in conformal field theory

    Energy Technology Data Exchange (ETDEWEB)

    Billò, Marco [Dipartimento di Fisica, Università di Torino, and Istituto Nazionale di Fisica Nucleare - sezione di Torino,Via P. Giuria 1 I-10125 Torino (Italy); Gonçalves, Vasco [Centro de Física do Porto,Departamento de Física e Astronomia Faculdade de Ciências da Universidade do Porto, Rua do Campo Alegre 687, 4169-007 Porto (Portugal); ICTP South American Institute for Fundamental Research Instituto de Física Teórica,UNESP - University Estadual Paulista,Rua Dr. Bento T. Ferraz 271, 01140-070, São Paulo, SP (Brazil); Lauria, Edoardo [Institute for Theoretical Physics, KU Leuven, Celestijnenlaan 200D, B-3001 Leuven (Belgium); Meineri, Marco [Perimeter Institute for Theoretical Physics,Waterloo, Ontario, N2L 2Y5 (Canada); Scuola Normale Superiore, and Istituto Nazionale di Fisica Nucleare - sezione di Pisa,Piazza dei Cavalieri 7 I-56126 Pisa (Italy)

    2016-04-15

    We discuss consequences of the breaking of conformal symmetry by a flat or spherical extended operator. We adapt the embedding formalism to the study of correlation functions of symmetric traceless tensors in the presence of the defect. Two-point functions of a bulk and a defect primary are fixed by conformal invariance up to a set of OPE coefficients, and we identify the allowed tensor structures. A correlator of two bulk primaries depends on two cross-ratios, and we study its conformal block decomposition in the case of external scalars. The Casimir equation in the defect channel reduces to a hypergeometric equation, while the bulk channel blocks are recursively determined in the light-cone limit. In the special case of a defect of codimension two, we map the Casimir equation in the bulk channel to the one of a four-point function without defect. Finally, we analyze the contact terms of the stress-tensor with the extended operator, and we deduce constraints on the CFT data. In two dimensions, we relate the displacement operator, which appears among the contact terms, to the reflection coefficient of a conformal interface, and we find unitarity bounds for the latter.

  1. Conformal symmetry and string theories

    International Nuclear Information System (INIS)

    Kumar, A.

    1987-01-01

    This thesis is devoted to the study of various aspects of the 2-dimensional conformal field theory and its applications to strings. We make a short review of the conformal field theory and its supersymmetric extension, called superconformal field theory. We present an elegant superspace formulation of these theories and solve the condition for the closure of the superconformal algebra. The we go on to classify the superconformal field theories according to these solutions. We prove that N ≥ 5 superconformal algebra, with N being the number of supersymmetries, does not have central charge. We find the primary representations of all the interesting superconformal algebra. We study the quantization of the superconformal theories and derive the constraints on the central charge of the algebra that has to be satisfied for a consistent quantum theory. This quantization process also determines the ground state energy of the system and the spectrum of the model. We study the global aspects of the conformal symmetry and its role in the construction of consistent heterotic string theories. We prove the uniqueness of heterotic superstring theories in 10 dimensions in the fermionic constructions. We show how the vertex operators are closely associated with the primary field representation of the conformal algebra. We utilize these vertex operator constructions to obtain tree amplitudes in the 10-dimensional heterotic string theory. We show by explicit calculation at the 3-point level that the scattering amplitudes derived from the heterotic superstring are same as the ones obtained from 10-dimensional supergravity theories

  2. Conformity index: A review

    International Nuclear Information System (INIS)

    Feuvret, Loic; Noel, Georges; Mazeron, Jean-Jacques; Bey, Pierre

    2006-01-01

    We present a critical analysis of the conformity indices described in the literature and an evaluation of their field of application. Three-dimensional conformal radiotherapy, with or without intensity modulation, is based on medical imaging techniques, three-dimensional dosimetry software, compression accessories, and verification procedures. It consists of delineating target volumes and critical healthy tissues to select the best combination of beams. This approach allows better adaptation of the isodose to the tumor volume, while limiting irradiation of healthy tissues. Tools must be developed to evaluate the quality of proposed treatment plans. Dosimetry software provides the dose distribution in each CT section and dose-volume histograms without really indicating the degree of conformity. The conformity index is a complementary tool that attributes a score to a treatment plan or that can compare several treatment plans for the same patient. The future of conformal index in everyday practice therefore remains unclear

  3. A threshold model for receptor tyrosine kinase signaling specificity and cell fate determination [version 1; referees: 4 approved

    Directory of Open Access Journals (Sweden)

    Allen Zinkle

    2018-06-01

    Full Text Available Upon ligand engagement, the single-pass transmembrane receptor tyrosine kinases (RTKs dimerize to transmit qualitatively and quantitatively different intracellular signals that alter the transcriptional landscape and thereby determine the cellular response. The molecular mechanisms underlying these fundamental events are not well understood. Considering recent insights into the structural biology of fibroblast growth factor signaling, we propose a threshold model for RTK signaling specificity in which quantitative differences in the strength/longevity of ligand-induced receptor dimers on the cell surface lead to quantitative differences in the phosphorylation of activation loop (A-loop tyrosines as well as qualitative differences in the phosphorylation of tyrosines mediating substrate recruitment. In this model, quantitative differences on A-loop tyrosine phosphorylation result in gradations in kinase activation, leading to the generation of intracellular signals of varying amplitude/duration. In contrast, qualitative differences in the pattern of tyrosine phosphorylation on the receptor result in the recruitment/activation of distinct substrates/intracellular pathways. Commensurate with both the dynamics of the intracellular signal and the types of intracellular pathways activated, unique transcriptional signatures are established. Our model provides a framework for engineering clinically useful ligands that can tune receptor dimerization stability so as to bias the cellular transcriptome to achieve a desired cellular output.

  4. In vivo dose estimations through transit signal measured with thimble chamber positioned along the central axis at electronic portal imaging device level in medical linear accelerator in carcinoma of the middle-third esophagus patients undergoing three-dimensional conformal radiotherapy.

    Science.gov (United States)

    Kumar, Putha Suman; Banerjee, S; Arun Kumar, E S; Srinivas, Challapalli; Vadhiraja, B M; Saxena, P U; Ravichandran, Ramamoorthy; Kasturi, Dinesh Pai

    2018-01-01

    This study presents a method to estimate midplane dose (D iso, transit ) in vivo from transit signal (S t ) measured with thimble ionization chamber in cancer of the middle-third esophagus patients treated with three-dimensional radiotherapy (RT). This detector is positioned at the level of electronic portal imaging device in the gantry of a medical linear accelerator. Efficacy of inhomogeneity corrections of three dose calculation algorithms available in XiO treatment planning system (TPS) for planned dose (for open fields) (D iso, TPS ) was studied with three heterogeneous phantoms. D iso, transit represents measured signal at transit point (S t ) far away correlating to dose at isocenter. A locally fabricated thorax phantom was used to measure the in vivo midplane dose (D iso, mid ) which was also estimated through S t . Thirteen patients with carcinoma of the middle-third esophagus treated with three-dimensional conformal RT were studied. S t was recorded (three times, with a gap of 5-6 fractions during the treatment) to estimate D iso, transit , which was compared with the doses calculated by TPS. The dose predictions by superposition algorithm were superior compared to the other algorithms. Percentage deviation of D iso, transit , D iso, mid with D iso, TPS combined all fields was 2.7 and -2.6%, respectively, with the thorax phantom. The mean percentage deviation with standard deviation of estimated D iso, transit with D iso, TPS observed in patients was within standard deviation -0.73% ±2.09% (n = 39). Midplane dose estimates in vivo using this method provide accurate determination of delivered dose in the middle-third esophagus RT treatments. This method could be useful in similar clinical circumstances for dose confirmation and documentation.

  5. Conformal invariance in supergravity

    International Nuclear Information System (INIS)

    Bergshoeff, E.A.

    1983-01-01

    In this thesis the author explains the role of conformal invariance in supergravity. He presents the complete structure of extended conformal supergravity for N <= 4. The outline of this work is as follows. In chapter 2 he briefly summarizes the essential properties of supersymmetry and supergravity and indicates the use of conformal invariance in supergravity. The idea that the introduction of additional symmetry transformations can make clear the structure of a field theory is not reserved to supergravity only. By means of some simple examples it is shown in chapter 3 how one can always introduce additional gauge transformations in a theory of massive vector fields. Moreover it is shown how the gauge invariant formulation sometimes explains the quantum mechanical properties of the theory. In chapter 4 the author defines the conformal transformations and summarizes their main properties. He explains how these conformal transformations can be used to analyse the structure of gravity. The supersymmetric extension of these results is discussed in chapter 5. Here he describes as an example how N=1 supergravity can be reformulated in a conformally-invariant way. He also shows that beyond N=1 the gauge fields of the superconformal symmetries do not constitute an off-shell field representation of extended conformal supergravity. Therefore, in chapter 6, a systematic method to construct the off-shell formulation of all extended conformal supergravity theories with N <= 4 is developed. As an example he uses this method to construct N=1 conformal supergravity. Finally, in chapter 7 N=4 conformal supergravity is discussed. (Auth.)

  6. Interplay between Dioxin-Mediated Signaling and Circadian Clock: A Possible Determinant in Metabolic Homeostasis

    Directory of Open Access Journals (Sweden)

    Chun Wang

    2014-07-01

    Full Text Available The rotation of the earth on its axis creates the environment of a 24 h solar day, which organisms on earth have used to their evolutionary advantage by integrating this timing information into their genetic make-up in the form of a circadian clock. This intrinsic molecular clock is pivotal for maintenance of synchronized homeostasis between the individual organism and the external environment to allow coordinated rhythmic physiological and behavioral function. Aryl hydrocarbon receptor (AhR is a master regulator of dioxin-mediated toxic effects, and is, therefore, critical in maintaining adaptive responses through regulating the expression of phase I/II drug metabolism enzymes. AhR expression is robustly rhythmic, and physiological cross-talk between AhR signaling and circadian rhythms has been established. Increasing evidence raises a compelling argument that disruption of endogenous circadian rhythms contributes to the development of disease, including sleep disorders, metabolic disorders and cancers. Similarly, exposure to environmental pollutants through air, water and food, is increasingly cited as contributory to these same problems. Thus, a better understanding of interactions between AhR signaling and the circadian clock regulatory network can provide critical new insights into environmentally regulated disease processes. This review highlights recent advances in the understanding of the reciprocal interactions between dioxin-mediated AhR signaling and the circadian clock including how these pathways relate to health and disease, with emphasis on the control of metabolic function.

  7. Determination of pseudo multi-pulse production rate in GM counters by correlation analysis between signal pulses

    International Nuclear Information System (INIS)

    Hashimoto, Kengo; Ueda, Taizou

    1996-01-01

    A technique, based on the correlation analysis of signal pulses in time sequence, is proposed to determine the production rate of the pseudo multi-pulse in Geiger-Mueller (GM) counter. With a multi-channel scaler initiated by a signal pulse, subsequent pulses are recorded in sequence. The production of the multi-pulse increases the counting probability immediately after the initiation. By examining the deviation of the measured probability from the ideal counting probability, the production rate and the average lag time to produce the multi-pulse can be determined. By the use of the present technique, the production rate and the average lag time were obtained for the various GM tubes. These results indicate that the consumption of the quench gas results in a significant increase in the production rate but little variation in the lag time, and that the lag time strongly depends on the tube diameter. (author)

  8. The C-terminal tail of CRTH2 is a key molecular determinant that constrains GalphaI- and downstream-signaling cascade activation

    DEFF Research Database (Denmark)

    Schroeder, Ralf; Merten, Nicole; Mathiesen, Jesper Mosolff

    2009-01-01

    Prostaglandin D(2) activation of the seven transmembrane receptor CRTH2 regulates numerous cell functions that are important in inflammatory diseases such as asthma. Despite its disease implication, no studies to date aimed at identifying receptor domains governing signaling and surface expression......2 at the plasma membrane, presence of this domain confers a signaling-compromised conformation onto the receptor. Indeed, a mutant receptor lacking the major portion of its C-terminal tail displays paradoxically enhanced Galphai and ERK1/2 activation in spite of enhanced constitutive and agonist......-mediated internalization. Enhanced activation of Galphai proteins and downstream signaling cascades is likely due to the inability of the tail-truncated receptor to recruit beta-arrestin2 and undergo homologous desensitization. Unexpectedly, CRTH2 is not phosphorylated upon agonist-stimulation, a primary mechanism...

  9. Conformal expansions and renormalons

    Energy Technology Data Exchange (ETDEWEB)

    Rathsman, J.

    2000-02-07

    The coefficients in perturbative expansions in gauge theories are factorially increasing, predominantly due to renormalons. This type of factorial increase is not expected in conformal theories. In QCD conformal relations between observables can be defined in the presence of a perturbative infrared fixed-point. Using the Banks-Zaks expansion the authors study the effect of the large-order behavior of the perturbative series on the conformal coefficients. The authors find that in general these coefficients become factorially increasing. However, when the factorial behavior genuinely originates in a renormalon integral, as implied by a postulated skeleton expansion, it does not affect the conformal coefficients. As a consequence, the conformal coefficients will indeed be free of renormalon divergence, in accordance with previous observations concerning the smallness of these coefficients for specific observables. The authors further show that the correspondence of the BLM method with the skeleton expansion implies a unique scale-setting procedure. The BLM coefficients can be interpreted as the conformal coefficients in the series relating the fixed-point value of the observable with that of the skeleton effective charge. Through the skeleton expansion the relevance of renormalon-free conformal coefficients extends to real-world QCD.

  10. Genetically determined measures of striatal D2 signaling predict prefrontal activity during working memory performance.

    Science.gov (United States)

    Bertolino, Alessandro; Taurisano, Paolo; Pisciotta, Nicola Marco; Blasi, Giuseppe; Fazio, Leonardo; Romano, Raffaella; Gelao, Barbara; Lo Bianco, Luciana; Lozupone, Madia; Di Giorgio, Annabella; Caforio, Grazia; Sambataro, Fabio; Niccoli-Asabella, Artor; Papp, Audrey; Ursini, Gianluca; Sinibaldi, Lorenzo; Popolizio, Teresa; Sadee, Wolfgang; Rubini, Giuseppe

    2010-02-22

    Variation of the gene coding for D2 receptors (DRD2) has been associated with risk for schizophrenia and with working memory deficits. A functional intronic SNP (rs1076560) predicts relative expression of the two D2 receptors isoforms, D2S (mainly pre-synaptic) and D2L (mainly post-synaptic). However, the effect of functional genetic variation of DRD2 on striatal dopamine D2 signaling and on its correlation with prefrontal activity during working memory in humans is not known. Thirty-seven healthy subjects were genotyped for rs1076560 (G>T) and underwent SPECT with [123I]IBZM (which binds primarily to post-synaptic D2 receptors) and with [123I]FP-CIT (which binds to pre-synaptic dopamine transporters, whose activity and density is also regulated by pre-synaptic D2 receptors), as well as BOLD fMRI during N-Back working memory. Subjects carrying the T allele (previously associated with reduced D2S expression) had striatal reductions of [123I]IBZM and of [123I]FP-CIT binding. DRD2 genotype also differentially predicted the correlation between striatal dopamine D2 signaling (as identified with factor analysis of the two radiotracers) and activity of the prefrontal cortex during working memory as measured with BOLD fMRI, which was positive in GG subjects and negative in GT. Our results demonstrate that this functional SNP within DRD2 predicts striatal binding of the two radiotracers to dopamine transporters and D2 receptors as well as the correlation between striatal D2 signaling with prefrontal cortex activity during performance of a working memory task. These data are consistent with the possibility that the balance of excitatory/inhibitory modulation of striatal neurons may also affect striatal outputs in relationship with prefrontal activity during working memory performance within the cortico-striatal-thalamic-cortical pathway.

  11. Genetically determined measures of striatal D2 signaling predict prefrontal activity during working memory performance.

    Directory of Open Access Journals (Sweden)

    Alessandro Bertolino

    2010-02-01

    Full Text Available Variation of the gene coding for D2 receptors (DRD2 has been associated with risk for schizophrenia and with working memory deficits. A functional intronic SNP (rs1076560 predicts relative expression of the two D2 receptors isoforms, D2S (mainly pre-synaptic and D2L (mainly post-synaptic. However, the effect of functional genetic variation of DRD2 on striatal dopamine D2 signaling and on its correlation with prefrontal activity during working memory in humans is not known.Thirty-seven healthy subjects were genotyped for rs1076560 (G>T and underwent SPECT with [123I]IBZM (which binds primarily to post-synaptic D2 receptors and with [123I]FP-CIT (which binds to pre-synaptic dopamine transporters, whose activity and density is also regulated by pre-synaptic D2 receptors, as well as BOLD fMRI during N-Back working memory.Subjects carrying the T allele (previously associated with reduced D2S expression had striatal reductions of [123I]IBZM and of [123I]FP-CIT binding. DRD2 genotype also differentially predicted the correlation between striatal dopamine D2 signaling (as identified with factor analysis of the two radiotracers and activity of the prefrontal cortex during working memory as measured with BOLD fMRI, which was positive in GG subjects and negative in GT.Our results demonstrate that this functional SNP within DRD2 predicts striatal binding of the two radiotracers to dopamine transporters and D2 receptors as well as the correlation between striatal D2 signaling with prefrontal cortex activity during performance of a working memory task. These data are consistent with the possibility that the balance of excitatory/inhibitory modulation of striatal neurons may also affect striatal outputs in relationship with prefrontal activity during working memory performance within the cortico-striatal-thalamic-cortical pathway.

  12. The Role of Retinal Determination Gene Network (RDGN) in Hormone Signaling Transduction and Prostate Tumorigenesis

    Science.gov (United States)

    2013-10-01

    Wu K, Wang L, Jiao X, Ju X, Li Z, Ertel A, Addya S, McCue P, Lisanti MP, Wang C, Davis RJ, Mardon G, Pestell RG. Androgen therapy resistant...Li Z, Hu J, Chen K, Wu J, Pestell RG. DACH1 inhibited prostate cancer cellular proliferation and Interleukon-6 signaling. AACR 103rd Annual Meeting...March 31 – April 4, 2012, Chicago, IL.  Wang J, Cai S, Chen K, Sun Y, Li S, Pestell RG, Wu K. Regulation of AR transcriptional activity and

  13. Conformal sequestering simplified

    International Nuclear Information System (INIS)

    Schmaltz, Martin; Sundrum, Raman

    2006-01-01

    Sequestering is important for obtaining flavor-universal soft masses in models where supersymmetry breaking is mediated at high scales. We construct a simple and robust class of hidden sector models which sequester themselves from the visible sector due to strong and conformally invariant hidden dynamics. Masses for hidden matter eventually break the conformal symmetry and lead to supersymmetry breaking by the mechanism recently discovered by Intriligator, Seiberg and Shih. We give a unified treatment of subtleties due to global symmetries of the CFT. There is enough review for the paper to constitute a self-contained account of conformal sequestering

  14. Conformally connected universes

    International Nuclear Information System (INIS)

    Cantor, M.; Piran, T.

    1983-01-01

    A well-known difficulty associated with the conformal method for the solution of the general relativistic Hamiltonian constraint is the appearance of an aphysical ''bag of gold'' singularity at the nodal surface of the conformal factor. This happens whenever the background Ricci scalar is too large. Using a simple model, it is demonstrated that some of these singular solutions do have a physical meaning, and that these can be considered as initial data for Universe containing black holes, which are connected, in a conformally nonsingular way with each other. The relation between the ADM mass and the horizon area in this solution supports the cosmic censorship conjecture. (author)

  15. Intensity modulated conformal radiotherapy

    International Nuclear Information System (INIS)

    Noel, Georges; Moty-Monnereau, Celine; Meyer, Aurelia; David, Pauline; Pages, Frederique; Muller, Felix; Lee-Robin, Sun Hae; David, Denis Jean

    2006-12-01

    This publication reports the assessment of intensity-modulated conformal radiotherapy (IMCR). This assessment is based on a literature survey which focussed on indications, efficiency and safety on the short term, on the risk of radio-induced cancer on the long term, on the role in the therapeutic strategy, on the conditions of execution, on the impact on morbidity-mortality and life quality, on the impact on the health system and on public health policies and program. This assessment is also based on the opinion of a group of experts regarding the technical benefit of IMCR, its indications depending on the cancer type, safety in terms of radio-induced cancers, and conditions of execution. Before this assessment, the report thus indicates indications for which the use of IMCR can be considered as sufficient or not determined. It also proposes a technical description of IMCR and helical tomo-therapy, discusses the use of this technique for various pathologies or tumours, analyses the present situation of care in France, and comments the identification of this technique in foreign classifications

  16. Structural and functional mapping of Rtg2p determinants involved in retrograde signaling and aging of Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Rafaela Maria Rios-Anjos

    Full Text Available In Saccharomyces cerevisiae mitochondrial dysfunction induces retrograde signaling, a pathway of communication from mitochondria to the nucleus that promotes a metabolic remodeling to ensure sufficient biosynthetic precursors for replication. Rtg2p is a positive modulator of this pathway that is also required for cellular longevity. This protein belongs to the ASKHA superfamily, and contains a putative N-terminal ATP-binding domain, but there is no detailed structural and functional map of the residues in this domain that accounts for their contribution to retrograde signaling and aging. Here we use Decomposition of Residue Correlation Networks and site-directed mutagenesis to identify Rtg2p structural determinants of retrograde signaling and longevity. We found that most of the residues involved in retrograde signaling surround the ATP-binding loops, and that Rtg2p N-terminus is divided in three regions whose mutants have different aging phenotypes. We also identified E137, D158 and S163 as possible residues involved in stabilization of ATP at the active site. The mutants shown here may be used to map other Rtg2p activities that crosstalk to other pathways of the cell related to genomic stability and aging.

  17. Conformable variational iteration method

    Directory of Open Access Journals (Sweden)

    Omer Acan

    2017-02-01

    Full Text Available In this study, we introduce the conformable variational iteration method based on new defined fractional derivative called conformable fractional derivative. This new method is applied two fractional order ordinary differential equations. To see how the solutions of this method, linear homogeneous and non-linear non-homogeneous fractional ordinary differential equations are selected. Obtained results are compared the exact solutions and their graphics are plotted to demonstrate efficiency and accuracy of the method.

  18. Delineating the conformal window

    DEFF Research Database (Denmark)

    Frandsen, Mads Toudal; Pickup, Thomas; Teper, Michael

    2011-01-01

    We identify and characterise the conformal window in gauge theories relevant for beyond the standard model building, e.g. Technicolour, using the criteria of metric confinement and causal analytic couplings, which are known to be consistent with the phase diagram of supersymmetric QCD from Seiberg...... duality. Using these criteria we find perturbation theory to be consistent throughout the predicted conformal window for several of these gauge theories and we discuss recent lattice results in the light of our findings....

  19. Determination of scattering center of multipath signals using geometric optics and Fresnel zone concepts

    Directory of Open Access Journals (Sweden)

    Kamil Yavuz Kapusuz

    2014-06-01

    Full Text Available In this study, a method for determining scattering center (or center of scattering points of a multipath is proposed, provided that the direction of arrival of the multipath is known by the receiver. The method is based on classical electromagnetic wave principles in order to determine scattering center over irregular terrain. Geometrical optics (GO along with Fresnel zone concept is employed, as the receiver, the transmitter positions and irregular terrain data are assumed to be provided. The proposed method could be used at UHF bands, especially, operations of radars and electronic warfare applications.

  20. Conformal-Based Surface Morphing and Multi-Scale Representation

    Directory of Open Access Journals (Sweden)

    Ka Chun Lam

    2014-05-01

    Full Text Available This paper presents two algorithms, based on conformal geometry, for the multi-scale representations of geometric shapes and surface morphing. A multi-scale surface representation aims to describe a 3D shape at different levels of geometric detail, which allows analyzing or editing surfaces at the global or local scales effectively. Surface morphing refers to the process of interpolating between two geometric shapes, which has been widely applied to estimate or analyze deformations in computer graphics, computer vision and medical imaging. In this work, we propose two geometric models for surface morphing and multi-scale representation for 3D surfaces. The basic idea is to represent a 3D surface by its mean curvature function, H, and conformal factor function λ, which uniquely determine the geometry of the surface according to Riemann surface theory. Once we have the (λ, H parameterization of the surface, post-processing of the surface can be done directly on the conformal parameter domain. In particular, the problem of multi-scale representations of shapes can be reduced to the signal filtering on the λ and H parameters. On the other hand, the surface morphing problem can be transformed to an interpolation process of two sets of (λ, H parameters. We test the proposed algorithms on 3D human face data and MRI-derived brain surfaces. Experimental results show that our proposed methods can effectively obtain multi-scale surface representations and give natural surface morphing results.

  1. Auxin transport, metabolism, and signalling during nodule initiation: indeterminate and determinate nodules

    NARCIS (Netherlands)

    Kohlen, W.; Ng, Jason Liang Pin; Deinum, E.E.; Mathesius, Ulrike

    2018-01-01

    Most legumes can form a unique type of lateral organ on their roots: root nodules. These structures host symbiotic nitrogen-fixing bacteria called rhizobia. Several different types of nodules can be found in nature, but the two best-studied types are called indeterminate and determinate nodules.

  2. On the physical origin of galactic conformity

    Science.gov (United States)

    Hearin, Andrew P.; Behroozi, Peter S.; van den Bosch, Frank C.

    2016-09-01

    Correlations between the star formation rates (SFRs) of nearby galaxies (so-called galactic conformity) have been observed for projected separations up to 4 Mpc, an effect not predicted by current semi-analytic models. We investigate correlations between the mass accretion rates (dMvir/dt) of nearby haloes as a potential physical origin for this effect. We find that pairs of host haloes `know about' each others' assembly histories even when their present-day separation is greater than thirty times the virial radius of either halo. These distances are far too large for direct interaction between the haloes to explain the correlation in their dMvir/dt. Instead, halo pairs at these distances reside in the same large-scale tidal environment, which regulates dMvir/dt for both haloes. Larger haloes are less affected by external forces, which naturally gives rise to a mass dependence of the halo conformity signal. SDSS measurements of galactic conformity exhibit a qualitatively similar dependence on stellar mass, including how the signal varies with distance. Based on the expectation that halo accretion and galaxy SFR are correlated, we predict the scale-, mass- and redshift-dependence of large-scale galactic conformity, finding that the signal should drop to undetectable levels by z ≳ 1. These predictions are testable with current surveys to z ˜ 1; confirmation would establish a strong correlation between dark matter halo accretion rate and central galaxy SFR.

  3. Dynamics Determine Signaling in a Multicomponent System Associated with Rheumatoid Arthritis.

    Science.gov (United States)

    Lindgren, Cecilia; Tyagi, Mohit; Viljanen, Johan; Toms, Johannes; Ge, Changrong; Zhang, Naru; Holmdahl, Rikard; Kihlberg, Jan; Linusson, Anna

    2018-05-24

    Strategies that target multiple components are usually required for treatment of diseases originating from complex biological systems. The multicomponent system consisting of the DR4 major histocompatibility complex type II molecule, the glycopeptide CII259-273 from type II collagen, and a T-cell receptor is associated with development of rheumatoid arthritis (RA). We introduced non-native amino acids and amide bond isosteres into CII259-273 and investigated the effect on binding to DR4 and the subsequent T-cell response. Molecular dynamics simulations revealed that complexes between DR4 and derivatives of CII259-273 were highly dynamic. Signaling in the overall multicomponent system was found to depend on formation of an appropriate number of dynamic intramolecular hydrogen bonds between DR4 and CII259-273, together with the positioning of the galactose moiety of CII259-273 in the DR4 binding groove. Interestingly, the system tolerated modifications at several positions in CII259-273, indicating opportunities to use analogues to increase our understanding of how rheumatoid arthritis develops and for evaluation as vaccines to treat RA.

  4. Determination of the conformation of 2-hydroxy- and 2-aminobenzoic acid dimers using 13C NMR and density functional theory/natural bond order analysis: the central importance of the carboxylic acid carbon.

    Science.gov (United States)

    Burnette, Ronald R; Weinhold, Frank

    2006-07-20

    The 13C chemical shift for the carboxylic acid carbon provides a powerful diagnostic probe to determine the preferred isomeric dimer structures of benzoic acid derivatives undergoing intra- and intermolecular H-bonding in the gas, solution and crystalline phases. We have employed hybrid density functional calculations and natural bond orbital analysis to elucidate the electronic origins of the observed 13C shieldings and their relationship to isomeric stability. We find that delocalizing interactions from the carbonyl oxygen lone pairs (nO) into vicinal carbon-oxygen and carbon-carbon antibonds (sigmaCO*,sigmaCC*) make critical contributions to the 13C shieldings, and these nO --> sigmaCO*, nO --> sigmaCC* interactions are in turn sensitive to the intramolecular interactions that dictate dimer structure and stability. The carboxyl carbon atom can thus serve as a useful detector of subtle structural and conformational features in this pharmacologically important class of carboxylic acid interactions.

  5. Signal quality indices and data fusion for determining clinical acceptability of electrocardiograms

    International Nuclear Information System (INIS)

    Clifford, G D; Behar, J; Li, Q; Rezek, I

    2012-01-01

    A completely automated algorithm to detect poor-quality electrocardiograms (ECGs) is described. The algorithm is based on both novel and previously published signal quality metrics, originally designed for intensive care monitoring. The algorithms have been adapted for use on short (5–10 s) single- and multi-lead ECGs. The metrics quantify spectral energy distribution, higher order moments and inter-channel and inter-algorithm agreement. Seven metrics were calculated for each channel (84 features in all) and presented to either a multi-layer perceptron artificial neural network or a support vector machine (SVM) for training on a multiple-annotator labelled and adjudicated training dataset. A single-lead version of the algorithm was also developed in a similar manner. Data were drawn from the PhysioNet Challenge 2011 dataset where binary labels were available, on 1500 12-lead ECGs indicating whether the entire recording was acceptable or unacceptable for clinical interpretation. We re-annotated all the leads in both the training set (1000 labelled ECGs) and test dataset (500 12-lead ECGs where labels were not publicly available) using two independent annotators, and a third for adjudication of differences. We found that low-quality data accounted for only 16% of the ECG leads. To balance the classes (between high and low quality), we created extra noisy data samples by adding noise from PhysioNet’s noise stress test database to some of the clean 12-lead ECGs. No data were shared between training and test sets. A classification accuracy of 98% on the training data and 97% on the test data were achieved. Upon inspection, incorrectly classified data were found to be borderline cases which could be classified either way. If these cases were more consistently labelled, we expect our approach to achieve an accuracy closer to 100%. (paper)

  6. Determination of the Rotational Barrier for Kinetically Stable Conformational Isomers via NMR and 2D TLC: An Introductory Organic Chemistry Experiment

    Science.gov (United States)

    Rushton, Gregory T.; Burns, William G.; Lavin, Judi M.; Chong, Yong S.; Pellechia, Perry; Shimizu, Ken D.

    2007-01-01

    An experiment to determine the rotational barrier about a C[subscript aryl]-N[subscript imide] single bond that is suitable for first-semester organic chemistry students is presented. The investigation begins with the one-step synthesis of a N,N'-diaryl naphthalene diimide, which exists as two room temperature-stable atropisomers (syn and anti).…

  7. Co-stimulatory signaling determines tumor antigen sensitivity and persistence of CAR T cells targeting PSCA+ metastatic prostate cancer.

    Science.gov (United States)

    Priceman, Saul J; Gerdts, Ethan A; Tilakawardane, Dileshni; Kennewick, Kelly T; Murad, John P; Park, Anthony K; Jeang, Brook; Yamaguchi, Yukiko; Yang, Xin; Urak, Ryan; Weng, Lihong; Chang, Wen-Chung; Wright, Sarah; Pal, Sumanta; Reiter, Robert E; Wu, Anna M; Brown, Christine E; Forman, Stephen J

    2018-01-01

    Advancing chimeric antigen receptor (CAR)-engineered adoptive T cells for the treatment of solid cancers is a major focus in the field of immunotherapy, given impressive recent clinical responses in hematological malignancies. Prostate cancer may be amenable to T cell-based immunotherapy since several tumor antigens, including prostate stem-cell antigen (PSCA), are widely over-expressed in metastatic disease. While antigen selectivity of CARs for solid cancers is crucial, it is problematic due to the absence of truly restricted tumor antigen expression and potential safety concerns with "on-target off-tumor" activity. Here, we show that the intracellular co-stimulatory signaling domain can determine a CAR's sensitivity for tumor antigen expression. A 4-1BB intracellular co-stimulatory signaling domain in PSCA-CARs confers improved selectivity for higher tumor antigen density, reduced T cell exhaustion phenotype, and equivalent tumor killing ability compared to PSCA-CARs containing the CD28 co-stimulatory signaling domain. PSCA-CARs exhibit robust in vivo anti-tumor activity in patient-derived bone-metastatic prostate cancer xenograft models, and 4-1BB-containing CARs show superior T cell persistence and control of disease compared with CD28-containing CARs. Our study demonstrates the importance of co-stimulation in defining an optimal CAR T cell, and also highlights the significance of clinically relevant models in developing solid cancer CAR T cell therapies.

  8. Co-stimulatory signaling determines tumor antigen sensitivity and persistence of CAR T cells targeting PSCA+ metastatic prostate cancer

    Science.gov (United States)

    Priceman, Saul J.; Gerdts, Ethan A.; Tilakawardane, Dileshni; Kennewick, Kelly T.; Murad, John P.; Park, Anthony K.; Jeang, Brook; Yamaguchi, Yukiko; Urak, Ryan; Weng, Lihong; Chang, Wen-Chung; Wright, Sarah; Pal, Sumanta; Reiter, Robert E.; Brown, Christine E.; Forman, Stephen J.

    2018-01-01

    ABSTRACT Advancing chimeric antigen receptor (CAR)-engineered adoptive T cells for the treatment of solid cancers is a major focus in the field of immunotherapy, given impressive recent clinical responses in hematological malignancies. Prostate cancer may be amenable to T cell-based immunotherapy since several tumor antigens, including prostate stem-cell antigen (PSCA), are widely over-expressed in metastatic disease. While antigen selectivity of CARs for solid cancers is crucial, it is problematic due to the absence of truly restricted tumor antigen expression and potential safety concerns with “on-target off-tumor” activity. Here, we show that the intracellular co-stimulatory signaling domain can determine a CAR's sensitivity for tumor antigen expression. A 4-1BB intracellular co-stimulatory signaling domain in PSCA-CARs confers improved selectivity for higher tumor antigen density, reduced T cell exhaustion phenotype, and equivalent tumor killing ability compared to PSCA-CARs containing the CD28 co-stimulatory signaling domain. PSCA-CARs exhibit robust in vivo anti-tumor activity in patient-derived bone-metastatic prostate cancer xenograft models, and 4-1BB-containing CARs show superior T cell persistence and control of disease compared with CD28-containing CARs. Our study demonstrates the importance of co-stimulation in defining an optimal CAR T cell, and also highlights the significance of clinically relevant models in developing solid cancer CAR T cell therapies. PMID:29308300

  9. Conformity and statistical tolerancing

    Science.gov (United States)

    Leblond, Laurent; Pillet, Maurice

    2018-02-01

    Statistical tolerancing was first proposed by Shewhart (Economic Control of Quality of Manufactured Product, (1931) reprinted 1980 by ASQC), in spite of this long history, its use remains moderate. One of the probable reasons for this low utilization is undoubtedly the difficulty for designers to anticipate the risks of this approach. The arithmetic tolerance (worst case) allows a simple interpretation: conformity is defined by the presence of the characteristic in an interval. Statistical tolerancing is more complex in its definition. An interval is not sufficient to define the conformance. To justify the statistical tolerancing formula used by designers, a tolerance interval should be interpreted as the interval where most of the parts produced should probably be located. This tolerance is justified by considering a conformity criterion of the parts guaranteeing low offsets on the latter characteristics. Unlike traditional arithmetic tolerancing, statistical tolerancing requires a sustained exchange of information between design and manufacture to be used safely. This paper proposes a formal definition of the conformity, which we apply successively to the quadratic and arithmetic tolerancing. We introduce a concept of concavity, which helps us to demonstrate the link between tolerancing approach and conformity. We use this concept to demonstrate the various acceptable propositions of statistical tolerancing (in the space decentring, dispersion).

  10. Axiomatic conformal field theory

    International Nuclear Information System (INIS)

    Gaberdiel, M.R.; Goddard, P.

    2000-01-01

    A new rigourous approach to conformal field theory is presented. The basic objects are families of complex-valued amplitudes, which define a meromorphic conformal field theory (or chiral algebra) and which lead naturally to the definition of topological vector spaces, between which vertex operators act as continuous operators. In fact, in order to develop the theory, Moebius invariance rather than full conformal invariance is required but it is shown that every Moebius theory can be extended to a conformal theory by the construction of a Virasoro field. In this approach, a representation of a conformal field theory is naturally defined in terms of a family of amplitudes with appropriate analytic properties. It is shown that these amplitudes can also be derived from a suitable collection of states in the meromorphic theory. Zhu's algebra then appears naturally as the algebra of conditions which states defining highest weight representations must satisfy. The relationship of the representations of Zhu's algebra to the classification of highest weight representations is explained. (orig.)

  11. UV conformal window for asymptotic safety

    Science.gov (United States)

    Bond, Andrew D.; Litim, Daniel F.; Vazquez, Gustavo Medina; Steudtner, Tom

    2018-02-01

    Interacting fixed points in four-dimensional gauge theories coupled to matter are investigated using perturbation theory up to three loop order. It is shown how fixed points, scaling exponents, and anomalous dimensions are obtained as a systematic power series in a small parameter. The underlying ordering principle is explained and contrasted with conventional perturbation theory and Weyl consistency conditions. We then determine the conformal window with asymptotic safety from the complete next-to-next-to-leading order in perturbation theory. Limits for the conformal window arise due to fixed point mergers, the onset of strong coupling, or vacuum instability. A consistent picture is uncovered by comparing various levels of approximation. The theory remains perturbative in the entire conformal window, with vacuum stability dictating the tightest constraints. We also speculate about a secondary conformal window at strong coupling and estimate its lower limit. Implications for model building and cosmology are indicated.

  12. Highly sensitive determination of atropine using cobalt oxide nanostructures: Influence of functional groups on the signal sensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Soomro, Razium Ali, E-mail: raziumsoomro@gmail.com [Interface Analysis Centre, School of Physics, University of Bristol, Bristol, BS8 1TL (United Kingdom); National Centre of Excellence in Analytical Chemistry, University of Sindh, Jamshoro, 76080 (Pakistan); Nafady, Ayman [Department of Chemistry, College of Science, King Saud University, Riyadh (Saudi Arabia); Department of Chemistry, Faculty of Science, Sohag University, Sohag (Egypt); Hallam, Keith Richard [Interface Analysis Centre, School of Physics, University of Bristol, Bristol, BS8 1TL (United Kingdom); Jawaid, Sana [National Centre of Excellence in Analytical Chemistry, University of Sindh, Jamshoro, 76080 (Pakistan); Al Enizi, Abdullah [Department of Chemistry, College of Science, King Saud University, Riyadh (Saudi Arabia); Sherazi, Syed Tufail Hussain; Sirajuddin [National Centre of Excellence in Analytical Chemistry, University of Sindh, Jamshoro, 76080 (Pakistan); Ibupoto, Zafar Hussain [Dr M.A. Kazi Institute of Chemistry, University of Sindh, Jamshoro, 76080 (Pakistan); Willander, Magnus [Department of Science and Technology, Campus Norrkoping, Linkoping University, SE-60174, Norrkoping (Sweden)

    2016-12-15

    This study describes sensitive determination of atropine using glassy carbon electrodes (GCE) modified with Co{sub 3}O{sub 4} nanostructures. The as-synthesised nanostructures were grown using cysteine (CYS), glutathione (GSH) and histidine (HYS) as effective templates under hydrothermal action. The obtained morphologies revealed interesting structural features, including both cavity-based and flower-shaped structures. The as-synthesised morphologies were noted to actively participate in electro-catalysis of atropine (AT) drug where GSH-assisted structures exhibited the best signal response in terms of current density and over-potential value. The study also discusses the influence of functional groups on the signal sensitivity of atropine electro-oxidation. The functionalisation was carried with the amino acids originally used as effective templates for the growth of Co{sub 3}O{sub 4} nanostructures. The highest increment was obtained when GSH was used as the surface functionalising agent. The GSH-functionalised Co{sub 3}O{sub 4}-modified electrode was utilised for the electro-chemical sensing of AT in a concentration range of 0.01–0.46 μM. The developed sensor exhibited excellent working linearity (R{sup 2} = 0.999) and signal sensitivity up to 0.001 μM of AT. The noted high sensitivity of the sensor is associated with the synergy of superb surface architectures and favourable interaction facilitating the electron transfer kinetics for the electro-catalytic oxidation of AT. Significantly, the developed sensor demonstrated excellent working capability when used for AT detection in human urine samples with strong anti-interference potential against common co-existing species, such as glucose, fructose, cysteine, uric acid, dopamine and ascorbic acid. - Highlights: • Template-assisted growth of Co{sub 3}O{sub 4} nanostructures. • Shape-dependent electro-catalysis of atropine. • Effect of functionalisation of signal sensitivity.

  13. Ras conformational switching: simulating nucleotide-dependent conformational transitions with accelerated molecular dynamics.

    Directory of Open Access Journals (Sweden)

    Barry J Grant

    2009-03-01

    Full Text Available Ras mediates signaling pathways controlling cell proliferation and development by cycling between GTP- and GDP-bound active and inactive conformational states. Understanding the complete reaction path of this conformational change and its intermediary structures is critical to understanding Ras signaling. We characterize nucleotide-dependent conformational transition using multiple-barrier-crossing accelerated molecular dynamics (aMD simulations. These transitions, achieved for the first time for wild-type Ras, are impossible to observe with classical molecular dynamics (cMD simulations due to the large energetic barrier between end states. Mapping the reaction path onto a conformer plot describing the distribution of the crystallographic structures enabled identification of highly populated intermediate structures. These structures have unique switch orientations (residues 25-40 and 57-75 intermediate between GTP and GDP states, or distinct loop3 (46-49, loop7 (105-110, and alpha5 C-terminus (159-166 conformations distal from the nucleotide-binding site. In addition, these barrier-crossing trajectories predict novel nucleotide-dependent correlated motions, including correlations of alpha2 (residues 66-74 with alpha3-loop7 (93-110, loop2 (26-37 with loop10 (145-151, and loop3 (46-49 with alpha5 (152-167. The interconversion between newly identified Ras conformations revealed by this study advances our mechanistic understanding of Ras function. In addition, the pattern of correlated motions provides new evidence for a dynamic linkage between the nucleotide-binding site and the membrane interacting C-terminus critical for the signaling function of Ras. Furthermore, normal mode analysis indicates that the dominant collective motion that occurs during nucleotide-dependent conformational exchange, and captured in aMD (but absent in cMD simulations, is a low-frequency motion intrinsic to the structure.

  14. Extended conformal algebras

    International Nuclear Information System (INIS)

    Goddard, Peter

    1990-01-01

    The algebra of the group of conformal transformations in two dimensions consists of two commuting copies of the Virasoro algebra. In many mathematical and physical contexts, the representations of ν which are relevant satisfy two conditions: they are unitary and they have the ''positive energy'' property that L o is bounded below. In an irreducible unitary representation the central element c takes a fixed real value. In physical contexts, the value of c is a characteristic of a theory. If c < 1, it turns out that the conformal algebra is sufficient to ''solve'' the theory, in the sense of relating the calculation of the infinite set of physically interesting quantities to a finite subset which can be handled in principle. For c ≥ 1, this is no longer the case for the algebra alone and one needs some sort of extended conformal algebra, such as the superconformal algebra. It is these algebras that this paper aims at addressing. (author)

  15. Algebraic conformal field theory

    International Nuclear Information System (INIS)

    Fuchs, J.; Nationaal Inst. voor Kernfysica en Hoge-Energiefysica

    1991-11-01

    Many conformal field theory features are special versions of structures which are present in arbitrary 2-dimensional quantum field theories. So it makes sense to describe 2-dimensional conformal field theories in context of algebraic theory of superselection sectors. While most of the results of the algebraic theory are rather abstract, conformal field theories offer the possibility to work out many formulae explicitly. In particular, one can construct the full algebra A-bar of global observables and the endomorphisms of A-bar which represent the superselection sectors. Some explicit results are presented for the level 1 so(N) WZW theories; the algebra A-bar is found to be the enveloping algebra of a Lie algebra L-bar which is an extension of the chiral symmetry algebra of the WZW theory. (author). 21 refs., 6 figs

  16. Virtual and solution conformations of oligosaccharides

    International Nuclear Information System (INIS)

    Cumming, D.A.; Carver, J.P.

    1987-01-01

    The possibility that observed nuclear Overhauser enhancements and bulk longitudinal relaxation times, parameters measured by 1 H NMR and often employed in determining the preferred solution conformation of biologically important molecules, are the result of averaging over many conformational states is quantitatively evaluated. Of particular interest was to ascertain whether certain 1 H NMR determined conformations are virtual in nature; i.e., the fraction of the population of molecules actually found at any time within the subset of conformational space defined as the solution conformation is vanishingly small. A statistical mechanics approach was utilized to calculate an ensemble average relaxation matrix from which (NOE)'s and (T 1 )'s are calculated. Model glycosidic linkages in four oligosaccharides were studied. The nature of the resultant population distributions is such that 50% of the molecular population is found within 1% of available microstates, while 99% of the molecular population occupies about 10% of the ensemble microstates, a number roughly equal to that sterically allowed. From this analysis the authors conclude that in many cases quantitative interpretation of NMR relaxation data, which attempts to define a single set of allowable torsion angle values consistent with the observed data, will lead to solution conformations that are either virtual or reflect torsion angle values possessed by a minority of the molecular population. Observed values of NMR relaxation data are the result of the complex interdependence of the population distribution and NOE (or T 1 ) surfaces in conformational space. In conformational analyses, NMR data can therefore be used to test different population distributions calculated from empirical potential energy functions

  17. 40 CFR 90.711 - Suspension and revocation of certificates of conformity.

    Science.gov (United States)

    2010-07-01

    ... certificates of conformity. 90.711 Section 90.711 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... conformity. (a) The certificate of conformity is suspended with respect to any engine failing pursuant to... suspend the certificate of conformity for an engine family which is determined to be in noncompliance...

  18. Determination of a PWR key neutron parameters uncertainties and conformity studies applications; Determination des incertitudes liees aux grandeurs neutroniques d'interet des reacteurs a eau pressurisee a plaques combustible et applications aux etudes de conformite

    Energy Technology Data Exchange (ETDEWEB)

    Bernard, D

    2002-07-01

    The aim of this thesis was to evaluate uncertainties of key neutron parameters of slab reactors. Uncertainties sources have many origins, technologic origin for parameters of fabrication and physical origin for nuclear data. First, each contribution of uncertainties is calculated and finally, a factor of uncertainties is associated to key slab parameter like reactivity, isotherm reactivity coefficient, control rod efficiency, power form factor before irradiation and lifetime. This factors of uncertainties were computed by Generalized Perturbations Theory in case of step 0 and by directs calculations in case of irradiation problems. One of neutronic conformity applications was about fabrication and nuclear data targets precision adjustments. Statistic (uncertainties) and deterministic (deviations) approaches were studied. Then neutronics key slab parameters uncertainties were reduced and so nuclear performances were optimised. (author)

  19. Determination of a PWR key neutron parameters uncertainties and conformity studies applications; Determination des incertitudes liees aux grandeurs neutroniques d'interet des reacteurs a eau pressurisee a plaques combustible et applications aux etudes de conformite

    Energy Technology Data Exchange (ETDEWEB)

    Bernard, D

    2002-07-01

    The aim of this thesis was to evaluate uncertainties of key neutron parameters of slab reactors. Uncertainties sources have many origins, technologic origin for parameters of fabrication and physical origin for nuclear data. First, each contribution of uncertainties is calculated and finally, a factor of uncertainties is associated to key slab parameter like reactivity, isotherm reactivity coefficient, control rod efficiency, power form factor before irradiation and lifetime. This factors of uncertainties were computed by Generalized Perturbations Theory in case of step 0 and by directs calculations in case of irradiation problems. One of neutronic conformity applications was about fabrication and nuclear data targets precision adjustments. Statistic (uncertainties) and deterministic (deviations) approaches were studied. Then neutronics key slab parameters uncertainties were reduced and so nuclear performances were optimised. (author)

  20. Net analyte signal standard addition method for simultaneous determination of sulphadiazine and trimethoprim in bovine milk and veterinary medicines.

    Science.gov (United States)

    Hajian, Reza; Mousavi, Esmat; Shams, Nafiseh

    2013-06-01

    Net analyte signal standard addition method has been used for the simultaneous determination of sulphadiazine and trimethoprim by spectrophotometry in some bovine milk and veterinary medicines. The method combines the advantages of standard addition method with the net analyte signal concept which enables the extraction of information concerning a certain analyte from spectra of multi-component mixtures. This method has some advantages such as the use of a full spectrum realisation, therefore it does not require calibration and prediction step and only a few measurements require for the determination. Cloud point extraction based on the phenomenon of solubilisation used for extraction of sulphadiazine and trimethoprim in bovine milk. It is based on the induction of micellar organised media by using Triton X-100 as an extraction solvent. At the optimum conditions, the norm of NAS vectors increased linearly with concentrations in the range of 1.0-150.0 μmolL(-1) for both sulphadiazine and trimethoprim. The limits of detection (LOD) for sulphadiazine and trimethoprim were 0.86 and 0.92 μmolL(-1), respectively. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. Killing tensors and conformal Killing tensors from conformal Killing vectors

    International Nuclear Information System (INIS)

    Rani, Raffaele; Edgar, S Brian; Barnes, Alan

    2003-01-01

    Koutras has proposed some methods to construct reducible proper conformal Killing tensors and Killing tensors (which are, in general, irreducible) when a pair of orthogonal conformal Killing vectors exist in a given space. We give the completely general result demonstrating that this severe restriction of orthogonality is unnecessary. In addition, we correct and extend some results concerning Killing tensors constructed from a single conformal Killing vector. A number of examples demonstrate that it is possible to construct a much larger class of reducible proper conformal Killing tensors and Killing tensors than permitted by the Koutras algorithms. In particular, by showing that all conformal Killing tensors are reducible in conformally flat spaces, we have a method of constructing all conformal Killing tensors, and hence all the Killing tensors (which will in general be irreducible) of conformally flat spaces using their conformal Killing vectors

  2. Global conformational dynamics of a Y-family DNA polymerase during catalysis.

    Directory of Open Access Journals (Sweden)

    Cuiling Xu

    2009-10-01

    Full Text Available Replicative DNA polymerases are stalled by damaged DNA while the newly discovered Y-family DNA polymerases are recruited to rescue these stalled replication forks, thereby enhancing cell survival. The Y-family DNA polymerases, characterized by low fidelity and processivity, are able to bypass different classes of DNA lesions. A variety of kinetic and structural studies have established a minimal reaction pathway common to all DNA polymerases, although the conformational intermediates are not well defined. Furthermore, the identification of the rate-limiting step of nucleotide incorporation catalyzed by any DNA polymerase has been a matter of long debate. By monitoring time-dependent fluorescence resonance energy transfer (FRET signal changes at multiple sites in each domain and DNA during catalysis, we present here a real-time picture of the global conformational transitions of a model Y-family enzyme: DNA polymerase IV (Dpo4 from Sulfolobus solfataricus. Our results provide evidence for a hypothetical DNA translocation event followed by a rapid protein conformational change prior to catalysis and a subsequent slow, post-chemistry protein conformational change. Surprisingly, the DNA translocation step was induced by the binding of a correct nucleotide. Moreover, we have determined the directions, rates, and activation energy barriers of the protein conformational transitions, which indicated that the four domains of Dpo4 moved in a synchronized manner. These results showed conclusively that a pre-chemistry conformational change associated with domain movements was too fast to be the rate-limiting step. Rather, the rearrangement of active site residues limited the rate of correct nucleotide incorporation. Collectively, the conformational dynamics of Dpo4 offer insights into how the inter-domain movements are related to enzymatic function and their concerted interactions with other proteins at the replication fork.

  3. Determination of PWR core water level using ex-core detectors signals

    International Nuclear Information System (INIS)

    Bernal, Alvaro; Abarca, Agustin; Miro, Rafael; Verdu, Gumersindo

    2013-01-01

    The core water level provides relevant neutronic and thermalhydraulic information of the reactor such as power, k eff and cooling ability; in fact, core water level monitoring could be used to predict LOCA and cooling reduction which may deal with core damage. Although different detection equipment is used to monitor several parameters such as the power, core water level monitoring is not an evident task. However, ex-core detectors can measure the fast neutrons leaking the core and several studies demonstrate the existence of a relationship between fast neutron leakage and core water level due to the shielding effect of the water. In addition, new ex-core detectors are being developed, such as silicon carbide semiconductor radiation detectors, monitoring the neutron flux with higher accuracy and in higher temperatures conditions. Therefore, a methodology to determine this relationship has been developed based on a Monte Carlo calculation using MCNP code and applying variance reduction with adjoint functions based on the adjoint flux obtained with the discrete ordinates code TORT. (author)

  4. Accurate Determination of Leucine and Valine Side-chain Conformations using U-[15N/13C/2H]/[1H-(methine/methyl)-Leu/Val] Isotope Labeling, NOE Pattern Recognition, and Methine Cγ-Hγ/Cβ-Hβ Residual Dipolar Couplings

    International Nuclear Information System (INIS)

    Tang, Chun; Iwahara, Junji; Clore, G. Marius

    2005-01-01

    An isotope labeling scheme is described in which specific protonation of methine and methyl protons of leucine and valine is obtained on a 15 N/ 13 C labeled background with uniform deuteration of all other non-exchangeable protons. The presence of a protonated methine group has little effect on the favorable relaxation properties of the methyl protons of Leu and Val. This labeling scheme permits the rotameric state of leucine side-chains to be readily determined by simple inspection of the pattern of Hγ(i)-H N (i) and Hγ(i)-H N (i+1) NOEs in a 3D 15 N-separated NOE spectrum free of complications arising from spectral overlap and spin-diffusion. In addition, one-bond residual dipolar couplings for the methine 13 C- 1 H bond vectors of Leu and Val can be accurately determined from an intensity J-modulated constant-time HCCH-COSY experiment and used to accurately orient the side-chains of Leu and Val. Incorporation of these data into structure refinement improves the accuracy with which the conformations of Leu and Val side-chains can be established. This is important to ensure optimal packing both within the protein core and at intermolecular interfaces. The impact of the method on protein structure determination is illustrated by application to enzyme IIA Chitobiose , a 34 kDa homotrimeric phosphotransferase protein

  5. Dll4-Notch signaling determines the formation of native arterial collateral networks and arterial function in mouse ischemia models.

    Science.gov (United States)

    Cristofaro, Brunella; Shi, Yu; Faria, Marcella; Suchting, Steven; Leroyer, Aurelie S; Trindade, Alexandre; Duarte, Antonio; Zovein, Ann C; Iruela-Arispe, M Luisa; Nih, Lina R; Kubis, Nathalie; Henrion, Daniel; Loufrani, Laurent; Todiras, Mihail; Schleifenbaum, Johanna; Gollasch, Maik; Zhuang, Zhen W; Simons, Michael; Eichmann, Anne; le Noble, Ferdinand

    2013-04-01

    Arteriogenesis requires growth of pre-existing arteriolar collateral networks and determines clinical outcome in arterial occlusive diseases. Factors responsible for the development of arteriolar collateral networks are poorly understood. The Notch ligand Delta-like 4 (Dll4) promotes arterial differentiation and restricts vessel branching. We hypothesized that Dll4 may act as a genetic determinant of collateral arterial networks and functional recovery in stroke and hind limb ischemia models in mice. Genetic loss- and gain-of-function approaches in mice showed that Dll4-Notch signaling restricts pial collateral artery formation by modulating arterial branching morphogenesis during embryogenesis. Adult Dll4(+/-) mice showed increased pial collateral numbers, but stroke volume upon middle cerebral artery occlusion was not reduced compared with wild-type littermates. Likewise, Dll4(+/-) mice showed reduced blood flow conductance after femoral artery occlusion, and, despite markedly increased angiogenesis, tissue ischemia was more severe. In peripheral arteries, loss of Dll4 adversely affected excitation-contraction coupling in arterial smooth muscle in response to vasopressor agents and arterial vessel wall adaption in response to increases in blood flow, collectively contributing to reduced flow reserve. We conclude that Dll4-Notch signaling modulates native collateral formation by acting on vascular branching morphogenesis during embryogenesis. Dll4 furthermore affects tissue perfusion by acting on arterial function and structure. Loss of Dll4 stimulates collateral formation and angiogenesis, but in the context of ischemic diseases such beneficial effects are overruled by adverse functional changes, demonstrating that ischemic recovery is not solely determined by collateral number but rather by vessel functionality.

  6. Dll4-Notch signaling determines the formation of native arterial collateral networks and arterial function in mouse ischemia models

    Science.gov (United States)

    Cristofaro, Brunella; Shi, Yu; Faria, Marcella; Suchting, Steven; Leroyer, Aurelie S.; Trindade, Alexandre; Duarte, Antonio; Zovein, Ann C.; Iruela-Arispe, M. Luisa; Nih, Lina R.; Kubis, Nathalie; Henrion, Daniel; Loufrani, Laurent; Todiras, Mihail; Schleifenbaum, Johanna; Gollasch, Maik; Zhuang, Zhen W.; Simons, Michael; Eichmann, Anne; le Noble, Ferdinand

    2013-01-01

    Arteriogenesis requires growth of pre-existing arteriolar collateral networks and determines clinical outcome in arterial occlusive diseases. Factors responsible for the development of arteriolar collateral networks are poorly understood. The Notch ligand Delta-like 4 (Dll4) promotes arterial differentiation and restricts vessel branching. We hypothesized that Dll4 may act as a genetic determinant of collateral arterial networks and functional recovery in stroke and hind limb ischemia models in mice. Genetic loss- and gain-of-function approaches in mice showed that Dll4-Notch signaling restricts pial collateral artery formation by modulating arterial branching morphogenesis during embryogenesis. Adult Dll4+/- mice showed increased pial collateral numbers, but stroke volume upon middle cerebral artery occlusion was not reduced compared with wild-type littermates. Likewise, Dll4+/- mice showed reduced blood flow conductance after femoral artery occlusion, and, despite markedly increased angiogenesis, tissue ischemia was more severe. In peripheral arteries, loss of Dll4 adversely affected excitation-contraction coupling in arterial smooth muscle in response to vasopressor agents and arterial vessel wall adaption in response to increases in blood flow, collectively contributing to reduced flow reserve. We conclude that Dll4-Notch signaling modulates native collateral formation by acting on vascular branching morphogenesis during embryogenesis. Dll4 furthermore affects tissue perfusion by acting on arterial function and structure. Loss of Dll4 stimulates collateral formation and angiogenesis, but in the context of ischemic diseases such beneficial effects are overruled by adverse functional changes, demonstrating that ischemic recovery is not solely determined by collateral number but rather by vessel functionality. PMID:23533173

  7. Massive Conformal Gravity

    International Nuclear Information System (INIS)

    Faria, F. F.

    2014-01-01

    We construct a massive theory of gravity that is invariant under conformal transformations. The massive action of the theory depends on the metric tensor and a scalar field, which are considered the only field variables. We find the vacuum field equations of the theory and analyze its weak-field approximation and Newtonian limit.

  8. Taming the conformal zoo

    International Nuclear Information System (INIS)

    Moore, G.; Seiberg, N.

    1989-01-01

    All known rational conformal field theories may be obtained from (2+1)-dimensional Chern-Simons gauge theories by appropriate choice of gauge group. We conjecture that all rational field theories are classified by groups via (2+1)-dimensional Chern-Simons gauge theories. (orig.)

  9. Conformal special relativity

    International Nuclear Information System (INIS)

    Maia, M.D.

    2006-01-01

    It is shown that the information loss/recovery theorem based on the ADS/CFT correspondence is not consistent with the stability of the Schwarzschild or Reissner-Nordstrom black holes. Nonetheless, the conformal invariance of Yang-Mills theory points to new relativity principle compatible with quantum unitarity near those black holes

  10. Animal culture: chimpanzee conformity?

    Science.gov (United States)

    van Schaik, Carel P

    2012-05-22

    Culture-like phenomena in wild animals have received much attention, but how good is the evidence and how similar are they to human culture? New data on chimpanzees suggest their culture may even have an element of conformity. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. Parafermionic conformal field theory

    International Nuclear Information System (INIS)

    Kurak, V.

    1989-09-01

    Conformal parafermionic field theories are reviewed with emphasis on the computation of their OPE estructure constants. It is presented a simple computational of these for the Z(N) parafermions, unveilling their Lie algebra content. (A.C.A.S.) [pt

  12. Quantifying polypeptide conformational space: sensitivity to conformation and ensemble definition.

    Science.gov (United States)

    Sullivan, David C; Lim, Carmay

    2006-08-24

    Quantifying the density of conformations over phase space (the conformational distribution) is needed to model important macromolecular processes such as protein folding. In this work, we quantify the conformational distribution for a simple polypeptide (N-mer polyalanine) using the cumulative distribution function (CDF), which gives the probability that two randomly selected conformations are separated by less than a "conformational" distance and whose inverse gives conformation counts as a function of conformational radius. An important finding is that the conformation counts obtained by the CDF inverse depend critically on the assignment of a conformation's distance span and the ensemble (e.g., unfolded state model): varying ensemble and conformation definition (1 --> 2 A) varies the CDF-based conformation counts for Ala(50) from 10(11) to 10(69). In particular, relatively short molecular dynamics (MD) relaxation of Ala(50)'s random-walk ensemble reduces the number of conformers from 10(55) to 10(14) (using a 1 A root-mean-square-deviation radius conformation definition) pointing to potential disconnections in comparing the results from simplified models of unfolded proteins with those from all-atom MD simulations. Explicit waters are found to roughen the landscape considerably. Under some common conformation definitions, the results herein provide (i) an upper limit to the number of accessible conformations that compose unfolded states of proteins, (ii) the optimal clustering radius/conformation radius for counting conformations for a given energy and solvent model, (iii) a means of comparing various studies, and (iv) an assessment of the applicability of random search in protein folding.

  13. Polo-like kinase phosphorylation determines Caenorhabditis elegans centrosome size and density by biasing SPD-5 toward an assembly-competent conformation

    Directory of Open Access Journals (Sweden)

    Oliver Wueseke

    2016-10-01

    Full Text Available Centrosomes are major microtubule-organizing centers composed of centrioles surrounded by an extensive proteinacious layer called the pericentriolar material (PCM. In Caenorhabditis elegans embryos, the mitotic PCM expands by Polo-like kinase 1 (PLK-1 phosphorylation-accelerated assembly of SPD-5 molecules into supramolecular scaffolds. However, how PLK-1 phosphorylation regulates SPD-5 assembly is not known. We found that a mutant version of SPD-5 that is insensitive to PLK-1 phosphorylation (SPD-54A could localize to PCM but was unable to rescue the reduction in PCM size and density when wild-type SPD-5 levels were decreased. In vitro, purified SPD-54A self-assembled into functional supramolecular scaffolds over long time scales, suggesting that phosphorylation only controls the rate of SPD-5 scaffold assembly. Furthermore, the SPD-5 scaffold, once assembled, remained intact and supported microtubule nucleation in the absence of PLK-1 activity in vivo. We conclude that PLK-1 is required for rapid assembly of the PCM scaffold but not for scaffold maintenance or function. Based on this idea, we developed a theoretical model that adequately predicted PCM growth rates in different mutant conditions in vivo. We propose that PLK-1 phosphorylation-dependent conversion of SPD-5 into an assembly-competent form underlies PCM formation in vivo and that the rate of this conversion determines final PCM size and density.

  14. Structural details (kinks and non-α conformations) in transmembrane helices are intrahelically determined and can be predicted by sequence pattern descriptors

    Science.gov (United States)

    Rigoutsos, Isidore; Riek, Peter; Graham, Robert M.; Novotny, Jiri

    2003-01-01

    One of the promising methods of protein structure prediction involves the use of amino acid sequence-derived patterns. Here we report on the creation of non-degenerate motif descriptors derived through data mining of training sets of residues taken from the transmembrane-spanning segments of polytopic proteins. These residues correspond to short regions in which there is a deviation from the regular α-helical character (i.e. π-helices, 310-helices and kinks). A ‘search engine’ derived from these motif descriptors correctly identifies, and discriminates amongst instances of the above ‘non-canonical’ helical motifs contained in the SwissProt/TrEMBL database of protein primary structures. Our results suggest that deviations from α-helicity are encoded locally in sequence patterns only about 7–9 residues long and can be determined in silico directly from the amino acid sequence. Delineation of such variations in helical habit is critical to understanding the complex structure–function relationships of polytopic proteins and for drug discovery. The success of our current methodology foretells development of similar prediction tools capable of identifying other structural motifs from sequence alone. The method described here has been implemented and is available on the World Wide Web at http://cbcsrv.watson.ibm.com/Ttkw.html. PMID:12888523

  15. Structural details (kinks and non-alpha conformations) in transmembrane helices are intrahelically determined and can be predicted by sequence pattern descriptors.

    Science.gov (United States)

    Rigoutsos, Isidore; Riek, Peter; Graham, Robert M; Novotny, Jiri

    2003-08-01

    One of the promising methods of protein structure prediction involves the use of amino acid sequence-derived patterns. Here we report on the creation of non-degenerate motif descriptors derived through data mining of training sets of residues taken from the transmembrane-spanning segments of polytopic proteins. These residues correspond to short regions in which there is a deviation from the regular alpha-helical character (i.e. pi-helices, 3(10)-helices and kinks). A 'search engine' derived from these motif descriptors correctly identifies, and discriminates amongst instances of the above 'non-canonical' helical motifs contained in the SwissProt/TrEMBL database of protein primary structures. Our results suggest that deviations from alpha-helicity are encoded locally in sequence patterns only about 7-9 residues long and can be determined in silico directly from the amino acid sequence. Delineation of such variations in helical habit is critical to understanding the complex structure-function relationships of polytopic proteins and for drug discovery. The success of our current methodology foretells development of similar prediction tools capable of identifying other structural motifs from sequence alone. The method described here has been implemented and is available on the World Wide Web at http://cbcsrv.watson.ibm.com/Ttkw.html.

  16. Driving Calmodulin Protein towards Conformational Shift by Changing Ionization States of Select Residues

    International Nuclear Information System (INIS)

    Negi, Sunita; Atilgan, Ali Rana; Atilgan, Canan

    2012-01-01

    Proteins are complex systems made up of many conformational sub-states which are mainly determined by the folded structure. External factors such as solvent type, temperature, pH and ionic strength play a very important role in the conformations sampled by proteins. Here we study the conformational multiplicity of calmodulin (CaM) which is a protein that plays an important role in calcium signaling pathways in the eukaryotic cells. CaM can bind to a variety of other proteins or small organic compounds, and mediates different physiological processes by activating various enzymes. Binding of calcium ions and proteins or small organic molecules to CaM induces large conformational changes that are distinct to each interacting partner. In particular, we discuss the effect of pH variation on the conformations of CaM. By using the pKa values of the charged residues as a basis to assign protonation states, the conformational changes induced in CaM by reducing the pH are studied by molecular dynamics simulations. Our current view suggests that at high pH, barrier crossing to the compact form is prevented by repulsive electrostatic interactions between the two lobes. At reduced pH, not only is barrier crossing facilitated by protonation of residues, but also conformations which are on average more compact are attained. The latter are in accordance with the fluorescence resonance energy transfer experiment results of other workers. The key events leading to the conformational change from the open to the compact conformation are (i) formation of a salt bridge between the N-lobe and the linker, stabilizing their relative motions, (ii) bending of the C-lobe towards the N-lobe, leading to a lowering of the interaction energy between the two-lobes, (iii) formation of a hydrophobic patch between the two lobes, further stabilizing the bent conformation by reducing the entropic cost of the compact form, (iv) sharing of a Ca +2 ion between the two lobes.

  17. Driving Calmodulin Protein towards Conformational Shift by Changing Ionization States of Select Residues

    Science.gov (United States)

    Negi, Sunita; Rana Atilgan, Ali; Atilgan, Canan

    2012-12-01

    Proteins are complex systems made up of many conformational sub-states which are mainly determined by the folded structure. External factors such as solvent type, temperature, pH and ionic strength play a very important role in the conformations sampled by proteins. Here we study the conformational multiplicity of calmodulin (CaM) which is a protein that plays an important role in calcium signaling pathways in the eukaryotic cells. CaM can bind to a variety of other proteins or small organic compounds, and mediates different physiological processes by activating various enzymes. Binding of calcium ions and proteins or small organic molecules to CaM induces large conformational changes that are distinct to each interacting partner. In particular, we discuss the effect of pH variation on the conformations of CaM. By using the pKa values of the charged residues as a basis to assign protonation states, the conformational changes induced in CaM by reducing the pH are studied by molecular dynamics simulations. Our current view suggests that at high pH, barrier crossing to the compact form is prevented by repulsive electrostatic interactions between the two lobes. At reduced pH, not only is barrier crossing facilitated by protonation of residues, but also conformations which are on average more compact are attained. The latter are in accordance with the fluorescence resonance energy transfer experiment results of other workers. The key events leading to the conformational change from the open to the compact conformation are (i) formation of a salt bridge between the N-lobe and the linker, stabilizing their relative motions, (ii) bending of the C-lobe towards the N-lobe, leading to a lowering of the interaction energy between the two-lobes, (iii) formation of a hydrophobic patch between the two lobes, further stabilizing the bent conformation by reducing the entropic cost of the compact form, (iv) sharing of a Ca+2 ion between the two lobes.

  18. Conformal Symmetry as a Template for QCD

    Energy Technology Data Exchange (ETDEWEB)

    Brodsky, S

    2004-08-04

    Conformal symmetry is broken in physical QCD; nevertheless, one can use conformal symmetry as a template, systematically correcting for its nonzero {beta} function as well as higher-twist effects. For example, commensurate scale relations which relate QCD observables to each other, such as the generalized Crewther relation, have no renormalization scale or scheme ambiguity and retain a convergent perturbative structure which reflects the underlying conformal symmetry of the classical theory. The ''conformal correspondence principle'' also dictates the form of the expansion basis for hadronic distribution amplitudes. The AdS/CFT correspondence connecting superstring theory to superconformal gauge theory has important implications for hadron phenomenology in the conformal limit, including an all-orders demonstration of counting rules for hard exclusive processes as well as determining essential aspects of hadronic light-front wavefunctions. Theoretical and phenomenological evidence is now accumulating that QCD couplings based on physical observables such as {tau} decay become constant at small virtuality; i.e., effective charges develop an infrared fixed point in contradiction to the usual assumption of singular growth in the infrared. The near-constant behavior of effective couplings also suggests that QCD can be approximated as a conformal theory even at relatively small momentum transfer. The importance of using an analytic effective charge such as the pinch scheme for unifying the electroweak and strong couplings and forces is also emphasized.

  19. Universal hydrodynamics of non-conformal branes

    International Nuclear Information System (INIS)

    Kanitscheider, Ingmar; Skenderis, Kostas

    2009-01-01

    We examine the hydrodynamic limit of non-conformal branes using the recently developed precise holographic dictionary. We first streamline the discussion of holography for backgrounds that asymptote locally to non-conformal brane solutions by showing that all such solutions can be obtained from higher dimensional asymptotically locally AdS solutions by suitable dimensional reduction and continuation in the dimension. As a consequence, many holographic results for such backgrounds follow from the corresponding results of the Asymptotically AdS case. In particular, the hydrodynamics of non-conformal branes is fully determined in terms of conformal hydrodynamics. Using previous results on the latter we predict the form of the non-conformal hydrodynamic stress tensor to second order in derivatives. Furthermore we show that the ratio between bulk and shear viscosity is fixed by the generalized conformal structure to be ζ/η = 2(1/(d-1)-c s 2 ), where c s is the speed of sound in the fluid.

  20. Conformal Symmetry as a Template for QCD

    International Nuclear Information System (INIS)

    Brodsky, S

    2004-01-01

    Conformal symmetry is broken in physical QCD; nevertheless, one can use conformal symmetry as a template, systematically correcting for its nonzero β function as well as higher-twist effects. For example, commensurate scale relations which relate QCD observables to each other, such as the generalized Crewther relation, have no renormalization scale or scheme ambiguity and retain a convergent perturbative structure which reflects the underlying conformal symmetry of the classical theory. The ''conformal correspondence principle'' also dictates the form of the expansion basis for hadronic distribution amplitudes. The AdS/CFT correspondence connecting superstring theory to superconformal gauge theory has important implications for hadron phenomenology in the conformal limit, including an all-orders demonstration of counting rules for hard exclusive processes as well as determining essential aspects of hadronic light-front wavefunctions. Theoretical and phenomenological evidence is now accumulating that QCD couplings based on physical observables such as τ decay become constant at small virtuality; i.e., effective charges develop an infrared fixed point in contradiction to the usual assumption of singular growth in the infrared. The near-constant behavior of effective couplings also suggests that QCD can be approximated as a conformal theory even at relatively small momentum transfer. The importance of using an analytic effective charge such as the pinch scheme for unifying the electroweak and strong couplings and forces is also emphasized

  1. Signals that determine internationalisation

    OpenAIRE

    Aryee, Esmeralda Na Momo; Henriquez Parodi, Massiel Carolina

    2017-01-01

    Master's thesis Business Administration BE501 - University of Agder 2017 International franchising business model is extensively and increasingly being used by entrepreneurs and firms seeking growth through geographic expansion. Thus, continued research efforts are needed to help entrepreneurs make wise choices when attracting investors into the business. Two popular theories (agency and resource scarcity) have been the basis on which international franchising has been explaine...

  2. Flat connection, conformal field theory and quantum group

    International Nuclear Information System (INIS)

    Kato, Mitsuhiro.

    1989-07-01

    General framework of linear first order differential equation for four-point conformal block is studied by using flat connection. Integrability and SL 2 invariance restrict possible form of flat connection. Under a special ansatz classical Yang-Baxter equation appears as an integrability condition and the WZW model turns to be unique conformal field theory in that case. Monodromy property of conformal block can be easily determined by the flat connection. 11 refs

  3. Study of polymer molecules and conformations with a nanopore

    Science.gov (United States)

    Golovchenko, Jene A.; Li, Jiali; Stein, Derek; Gershow, Marc H.

    2010-12-07

    The invention features methods for evaluating the conformation of a polymer, for example, for determining the conformational distribution of a plurality of polymers and to detect binding or denaturation events. The methods employ a nanopore which the polymer, e.g., a nucleic acid, traverses. As the polymer traverses the nanopore, measurements of transport properties of the nanopore yield data on the conformation of the polymer.

  4. Transportation Conformity Training and Presentations

    Science.gov (United States)

    EPA's OTAQ has provided multiple conformity training sessions in the past to assist state and local governments in implementing conformity requirements. As training information is prepared for other venues, it will be posted on this page.

  5. Hot Conformal Gauge Theories

    DEFF Research Database (Denmark)

    Mojaza, Matin; Pica, Claudio; Sannino, Francesco

    2010-01-01

    of flavors. Surprisingly this number, if computed to the order g^2, agrees with previous predictions for the lower boundary of the conformal window for nonsupersymmetric gauge theories. The higher order results tend to predict a higher number of critical flavors. These are universal properties, i......We compute the nonzero temperature free energy up to the order g^6 \\ln(1/g) in the coupling constant for vector like SU(N) gauge theories featuring matter transforming according to different representations of the underlying gauge group. The number of matter fields, i.e. flavors, is arranged...... in such a way that the theory develops a perturbative stable infrared fixed point at zero temperature. Due to large distance conformality we trade the coupling constant with its fixed point value and define a reduced free energy which depends only on the number of flavors, colors and matter representation. We...

  6. Conformational flexibility of aspartame.

    Science.gov (United States)

    Toniolo, Claudio; Temussi, Pierandrea

    2016-05-01

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

  7. Conformal description of spinning particles

    International Nuclear Information System (INIS)

    Todorov, I.T.

    1986-01-01

    This book is an introduction to the application of the conformal group to quantum field theory of particles with spin. After an introduction to the twistor representations of the conformal group of a conformally flat space-time and twistor flag manifolds with Su(2,2) orbits the classical phase space of conformal spinning particles is described. Thereafter the twistor description of classical zero mass fields is considered together with the quantization. (HSI)

  8. Conformal radiotherapy: a glossary

    International Nuclear Information System (INIS)

    Dubray, B.; Giraud, P.; Beaudre, A.

    1999-01-01

    Most of the concepts and terms related to conformal radiotherapy were produced by English-speaking authors and eventually validated by international groups of experts, whose working language was also English. Therefore, a significant part of this literature is poorly accessible to the French-speaking radiation oncology community. The present paper gathers the 'official' definitions already published in French, along with propositions for the remaining terms which should be submitted to a more formal and representative validation process. (author)

  9. Biased Gs Versus Gq Proteins and β-Arrestin Signaling in the NK1 Receptor Determined by Interactions in the Water Hydrogen Bond Network

    DEFF Research Database (Denmark)

    Valentin-Hansen, Louise; Frimurer, Thomas M; Mokrosinski, Jacek

    2015-01-01

    X-ray structures, molecular dynamics simulations, and mutational analysis have previously indicated that an extended water hydrogen bond network between trans-membranes I-III, VI, and VII constitutes an allosteric interface essential for stabilizing different active and inactive helical...... of the highly conserved AspII:10 (2.50). Here, we find that this GluII:10 occupies the space of a putative allosteric modulating Na(+) ion and makes direct inter-helical interactions in particular with SerIII:15 (3.39) and AsnVII:16 (7.49) of the NPXXY motif. Mutational changes in the interface between GluII:10....... It is concluded that the interface between position II:10 (2.50), III:15 (3.39), and VII:16 (7.49) in the center of the water hydrogen bond network constitutes a focal point for fine-tuning seven trans-membrane receptor conformations activating different signal transduction pathways....

  10. Hollow nanogold microsphere-signalized lateral flow immuno dipstick for the sensitive determination of the neurotoxin brevetoxin B

    International Nuclear Information System (INIS)

    Zhang, Kangyao; Wu, Jiachang; Li, Yineng; Wu, Yarong; Huang, Tianfu; Tang, Dianping

    2014-01-01

    We report on a new membrane-based lateral-flow assay for the rapid determination of the algal biotoxin brevetoxin B (BrevTox) that can be found in fish. Hollow nanogold microspheres (HGMS) with an average size of 45 nm were synthesized by using the reverse micelle method, followed by functionalization with monoclonal mouse anti-BrevTox antibody (mAb-HGMS). They served as the signalling reagent. Bovine serum albumin-BrevTox conjugate and rabbit anti-mouse IgG antibody were manually spotted on the nitrocellulose membrane and served as reagents for the test line and control line, respectively. Both spherical gold nanoparticle-labeled anti-BrevTox antibody (mAb-AuNP) and mAb-HGMS conjugate were investigated with respect to their suitability as signal-transduction tags, and the latter was found to give improved analytical features. The HGMS-based labeling method was then also studied in terms of performance in the immuno dipstick assay. Under optimal conditions, the visual detection limit (cut-off value) of the mAb-AuNP based assay is 1.5 ng mL −1 , while the sensitivity of the mAb-HGMS based assay is as low as 0.1 ng mL −1 . Yes/no decisions can be made within 10 min without the need for expensive instrumentation. The results for the analysis of target BrevTox in spiked fish samples showed a good correlation with data obtained with the commercial ELISA. Importantly, the assay gave no false negative results. (author)

  11. Photoplethysmography Signal Analysis for Optimal Region-of-Interest Determination in Video Imaging on a Built-In Smartphone under Different Conditions

    Directory of Open Access Journals (Sweden)

    Yunyoung Nam

    2017-10-01

    Full Text Available Smartphones and tablets are widely used in medical fields, which can improve healthcare and reduce healthcare costs. Many medical applications for smartphones and tablets have already been developed and widely used by both health professionals and patients. Specifically, video recordings of fingertips made using a smartphone camera contain a pulsatile component caused by the cardiac pulse equivalent to that present in a photoplethysmographic signal. By performing peak detection on the pulsatile signal, it is possible to estimate a continuous heart rate and a respiratory rate. To estimate the heart rate and respiratory rate accurately, which pixel regions of the color bands give the most optimal signal quality should be investigated. In this paper, we investigate signal quality to determine the best signal quality by the largest amplitude values for three different smartphones under different conditions. We conducted several experiments to obtain reliable PPG signals and compared the PPG signal strength in the three color bands when the flashlight was both on and off. We also evaluated the intensity changes of PPG signals obtained from the smartphones with motion artifacts and fingertip pressure force. Furthermore, we have compared the PSNR of PPG signals of the full-size images with that of the region of interests (ROIs.

  12. Conformally covariant composite operators in quantum chromodynamics

    International Nuclear Information System (INIS)

    Craigie, N.S.; Dobrev, V.K.; Todorov, I.T.

    1983-03-01

    Conformal covariance is shown to determine renormalization properties of composite operators in QCD and in the C 6 3 -model at the one-loop level. Its relevance to higher order (renormalization group improved) perturbative calculations in the short distance limit is also discussed. Light cone operator product expansions and spectral representations for wave functions in QCD are derived. (author)

  13. Local supertwistors and N=2 conformal supergravity

    International Nuclear Information System (INIS)

    Merkulov, S.A.

    1989-01-01

    N = 2 sypersymmetric extension of the local twistor theory is formulated. A supertwistor superconnection determined by the superconformal structure of the base superspace is introduced on the bundle of N = 2 local supertwistors. It is proved that the Yang - Mills equations for this superconnection coincide exactly with the Bach equations describing the dynamics of N 2 conformal supergravity

  14. Conformity to the Surviving Sepsis Campaign International ...

    African Journals Online (AJOL)

    Background: There are emerging therapies for managing septic critically-ill patients. There is little data from the developing world on their usage. Objectives: To determine the conformity rate for resuscitation and management bundles for septic patients amongst physicians in a general intensive care unit. Design: Cross ...

  15. Nonperturbative results for two-index conformal windows

    International Nuclear Information System (INIS)

    Bergner, Georg; Ryttov, Thomas A.; Sannino, Francesco

    2015-01-01

    Via large and small N c relations we derive nonperturbative results about the conformal window of two-index theories. Using Schwinger-Dyson methods as well as four-loops results we estimate subleading corrections and show that naive large number of colors extrapolations are unreliable when N c is less than about six. Nevertheless useful nonperturbative inequalities for the size of the conformal windows, for any number of colors, can be derived. By further observing that the adjoint conformal window is independent of the number of colors we argue, among other things, that: the large N c two-index conformal window is twice the conformal window of the adjoint representation (which can be determined at small N c ) expressed in terms of Dirac fermions; lattice results for adjoint matter can be used to provide independent information on the conformal dynamics of two-index theories such as SU(N c ) with two and four symmetric Dirac flavors.

  16. Nilpotent weights in conformal field theory

    Directory of Open Access Journals (Sweden)

    S. Rouhani

    2001-12-01

    Full Text Available   Logarithmic conformal field theory can be obtained using nilpotent weights. Using such scale transformations various properties of the theory were derived. The derivation of four point function needs a knowledge of singular vectors which is derived by including nilpotent variables into the Kac determinant. This leads to inhomogeneous hypergeometric functions. Finally we consider the theory near a boundary and also introduce the concept of superfields where a multiplet of conformal fields are dealt with together. This leads to the OPE of superfields and a logarithmic partner for the energy momentum tensor.

  17. Conformal invariance in quantum field theory

    International Nuclear Information System (INIS)

    Grensing, G.

    1978-01-01

    We study the transformation law of interacting fields under the universal covering group of the conformal group. It is defined with respect to the representations of the discrete series. These representations are field representations in the sense that they act on finite component fields defined over Minkowski space. The conflict with Einstein causality is avoided as in the case of free fields with canonical dimension. Furthermore, we determine the conformal invariant two-point function of arbitrary spin. Our result coincides with that obtained by Ruehl. In particular, we investigate the two-point function of symmetric and traceless tensor fields and give the explicit form of the trace terms

  18. Conformational analysis by intersection: CONAN.

    Science.gov (United States)

    Smellie, Andrew; Stanton, Robert; Henne, Randy; Teig, Steve

    2003-01-15

    As high throughput techniques in chemical synthesis and screening improve, more demands are placed on computer assisted design and virtual screening. Many of these computational methods require one or more three-dimensional conformations for molecules, creating a demand for a conformational analysis tool that can rapidly and robustly cover the low-energy conformational spaces of small molecules. A new algorithm of intersection is presented here, which quickly generates (on average heuristics are applied after intersection to generate a small representative collection of conformations that span the conformational space. In a study of approximately 97,000 randomly selected molecules from the MDDR, results are presented that explore these conformations and their ability to cover low-energy conformational space. Copyright 2002 Wiley Periodicals, Inc. J Comput Chem 24: 10-20, 2003

  19. Conformal superalgebras via tractor calculus

    Science.gov (United States)

    Lischewski, Andree

    2015-01-01

    We use the manifestly conformally invariant description of a Lorentzian conformal structure in terms of a parabolic Cartan geometry in order to introduce a superalgebra structure on the space of twistor spinors and normal conformal vector fields formulated in purely algebraic terms on parallel sections in tractor bundles. Via a fixed metric in the conformal class, one reproduces a conformal superalgebra structure that has been considered in the literature before. The tractor approach, however, makes clear that the failure of this object to be a Lie superalgebra in certain cases is due to purely algebraic identities on the spinor module and to special properties of the conformal holonomy representation. Moreover, it naturally generalizes to higher signatures. This yields new formulas for constructing new twistor spinors and higher order normal conformal Killing forms out of existing ones, generalizing the well-known spinorial Lie derivative. Moreover, we derive restrictions on the possible dimension of the space of twistor spinors in any metric signature.

  20. Twistor space, Minkowski space and the conformal group

    NARCIS (Netherlands)

    van den Broek, P.M.

    1983-01-01

    It is shown that the conformal group of compactified Minkowski space is isomorphic to a group of rays of semilinear transformations of twistor space. The action of the conformal group on twistor space is given by an explicit realisation of this isomorphism. In this way we determine the

  1. Twistor space, Minkowski space and the conformal group

    International Nuclear Information System (INIS)

    Broek, P.M. van den

    1983-01-01

    It is shown that the conformal group of compactified Minkowski space is isomorphic to a group of rays of semilinear transformations of twistor space. The action of the conformal group on twistor space is given by an explicit realisation of this isomorphism. In this way we determine the transformation of twistor space under space inversion and time inversion. (orig.)

  2. 40 CFR 93.161 - Conformity evaluation for Federal installations with facility-wide emission budgets.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Conformity evaluation for Federal... PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) DETERMINING CONFORMITY OF FEDERAL ACTIONS TO STATE OR FEDERAL IMPLEMENTATION PLANS Determining Conformity of General Federal Actions to State or Federal...

  3. Classical extended conformal symmetries

    International Nuclear Information System (INIS)

    Viswanathan, R.

    1990-02-01

    Extensions of the Virasoro algebra are constructed as Poisson brackets of higher spin fields which appear as coefficient fields in certain covariant derivative operators of order N. These differential operators are constructed so as to be covariant under reparametrizations on fields of definite conformal dimension. Factorization of such an N-th order operator in terms of first order operators, together with the inclusion of a spin one U(1) current, is shown to lead to a two-parameter W-algebra. One of these parameters plays the role of interpolating between W-algebras based on different Lie algebras of the same rank. (author). 11 refs

  4. Conformally symmetric traversable wormholes

    International Nuclear Information System (INIS)

    Boehmer, Christian G.; Harko, Tiberiu; Lobo, Francisco S. N.

    2007-01-01

    Exact solutions of traversable wormholes are found under the assumption of spherical symmetry and the existence of a nonstatic conformal symmetry, which presents a more systematic approach in searching for exact wormhole solutions. In this work, a wide variety of solutions are deduced by considering choices for the form function, a specific linear equation of state relating the energy density and the pressure anisotropy, and various phantom wormhole geometries are explored. A large class of solutions impose that the spatial distribution of the exotic matter is restricted to the throat neighborhood, with a cutoff of the stress-energy tensor at a finite junction interface, although asymptotically flat exact solutions are also found. Using the 'volume integral quantifier', it is found that the conformally symmetric phantom wormhole geometries may, in principle, be constructed by infinitesimally small amounts of averaged null energy condition violating matter. Considering the tidal acceleration traversability conditions for the phantom wormhole geometry, specific wormhole dimensions and the traversal velocity are also deduced

  5. Supergravitational conformal Galileons

    Science.gov (United States)

    Deen, Rehan; Ovrut, Burt

    2017-08-01

    The worldvolume actions of 3+1 dimensional bosonic branes embedded in a five-dimensional bulk space can lead to important effective field theories, such as the DBI conformal Galileons, and may, when the Null Energy Condition is violated, play an essential role in cosmological theories of the early universe. These include Galileon Genesis and "bouncing" cosmology, where a pre-Big Bang contracting phase bounces smoothly to the presently observed expanding universe. Perhaps the most natural arena for such branes to arise is within the context of superstring and M -theory vacua. Here, not only are branes required for the consistency of the theory, but, in many cases, the exact spectrum of particle physics occurs at low energy. However, such theories have the additional constraint that they must be N = 1 supersymmetric. This motivates us to compute the worldvolume actions of N = 1 supersymmetric three-branes, first in flat superspace and then to generalize them to N = 1 supergravitation. In this paper, for simplicity, we begin the process, not within the context of a superstring vacuum but, rather, for the conformal Galileons arising on a co-dimension one brane embedded in a maximally symmetric AdS 5 bulk space. We proceed to N = 1 supersymmetrize the associated worldvolume theory and then generalize the results to N = 1 supergravity, opening the door to possible new cosmological scenarios

  6. Morphogen and community effects determine cell fates in response to BMP4 signaling in human embryonic stem cells.

    Science.gov (United States)

    Nemashkalo, Anastasiia; Ruzo, Albert; Heemskerk, Idse; Warmflash, Aryeh

    2017-09-01

    Paracrine signals maintain developmental states and create cell fate patterns in vivo and influence differentiation outcomes in human embryonic stem cells (hESCs) in vitro Systematic investigation of morphogen signaling is hampered by the difficulty of disentangling endogenous signaling from experimentally applied ligands. Here, we grow hESCs in micropatterned colonies of 1-8 cells ('µColonies') to quantitatively investigate paracrine signaling and the response to external stimuli. We examine BMP4-mediated differentiation in µColonies and standard culture conditions and find that in µColonies, above a threshold concentration, BMP4 gives rise to only a single cell fate, contrary to its role as a morphogen in other developmental systems. Under standard culture conditions BMP4 acts as a morphogen but this requires secondary signals and particular cell densities. We find that a 'community effect' enforces a common fate within µColonies, both in the state of pluripotency and when cells are differentiated, and that this effect allows a more precise response to external signals. Using live cell imaging to correlate signaling histories with cell fates, we demonstrate that interactions between neighbors result in sustained, homogenous signaling necessary for differentiation. © 2017. Published by The Company of Biologists Ltd.

  7. IgG Fab Fragments Forming Bivalent Complexes by a Conformational Mechanism That Is Reversible by Osmolytes*

    Science.gov (United States)

    Nelson, Alfreda D.; Hoffmann, Michele M.; Parks, Christopher A.; Dasari, Surendra; Schrum, Adam G.; Gil, Diana

    2012-01-01

    Generated by proteolytic cleavage of immunoglobulin, Fab fragments possess great promise as blocking reagents, able to bind receptors or other targets without inducing cross-linking. However, aggregation of Fab preparations is a common occurrence, which generates intrinsic stimulatory capacity and thwarts signal blockade strategies. Using a panel of biochemical approaches, including size exclusion chromatography, SDS-PAGE, mass spectrometry, and cell stimulation followed by flow cytometry, we have measured the oligomerization and acquisition of stimulatory capacity that occurs in four monoclonal IgG Fabs specific for TCR/CD3. Unexpectedly, we observed that all Fabs spontaneously formed complexes that were precisely bivalent, and these bivalent complexes possessed most of the stimulatory activity of each Fab preparation. Fabs composing bivalent complexes were more susceptible to proteolysis than monovalent Fabs, indicating a difference in conformation between the Fabs involved in these two different states of valency. Because osmolytes represent a class of compounds that stabilize protein folding and conformation, we sought to determine the extent to which the amino acid osmolyte l-proline might impact bivalent Fab complexation. We found that l-proline (i) inhibited the adoption of the conformation associated with bivalent complexation, (ii) preserved Fab monovalency, (iii) reversed the conformation of preformed bivalent Fabs to that of monovalent Fabs, and (iv) separated a significant percentage of preformed bivalent complexes into monovalent species. Thus, Fab fragments can adopt a conformation that is compatible with folding or packing of a bivalent complex in a process that can be inhibited by osmolytes. PMID:23109335

  8. DNA minor groove electrostatic potential: influence of sequence-specific transitions of the torsion angle gamma and deoxyribose conformations.

    Science.gov (United States)

    Zhitnikova, M Y; Shestopalova, A V

    2017-11-01

    The structural adjustments of the sugar-phosphate DNA backbone (switching of the γ angle (O5'-C5'-C4'-C3') from canonical to alternative conformations and/or C2'-endo → C3'-endo transition of deoxyribose) lead to the sequence-specific changes in accessible surface area of both polar and non-polar atoms of the grooves and the polar/hydrophobic profile of the latter ones. The distribution of the minor groove electrostatic potential is likely to be changing as a result of such conformational rearrangements in sugar-phosphate DNA backbone. Our analysis of the crystal structures of the short free DNA fragments and calculation of their electrostatic potentials allowed us to determine: (1) the number of classical and alternative γ angle conformations in the free B-DNA; (2) changes in the minor groove electrostatic potential, depending on the conformation of the sugar-phosphate DNA backbone; (3) the effect of the DNA sequence on the minor groove electrostatic potential. We have demonstrated that the structural adjustments of the DNA double helix (the conformations of the sugar-phosphate backbone and the minor groove dimensions) induce changes in the distribution of the minor groove electrostatic potential and are sequence-specific. Therefore, these features of the minor groove sizes and distribution of minor groove electrostatic potential can be used as a signal for recognition of the target DNA sequence by protein in the implementation of the indirect readout mechanism.

  9. Ward identities for conformal models

    International Nuclear Information System (INIS)

    Lazzarini, S.; Stora, R.

    1988-01-01

    Ward identities which express the symmetry of conformal models are treated. Diffeomorphism invariance or locally holomorphic coordinate transformations are used. Diffeomorphism invariance is then understood in terms of Riemannian geometry. Two different sets of Ward identities expressing diffeomorphism invariance in a conformally invariant way are found for the free bosonic string. Using a geometrical argument, the correct invariance for a large class of conformal models is given

  10. Conformational analysis of lignin models

    International Nuclear Information System (INIS)

    Santos, Helio F. dos

    2001-01-01

    The conformational equilibrium for two 5,5' biphenyl lignin models have been analyzed using a quantum mechanical semiempirical method. The gas phase and solution structures are discussed based on the NMR and X-ray experimental data. The results obtained showed that the observed conformations are solvent-dependent, being the geometries and the thermodynamic properties correlated with the experimental information. This study shows how a systematic theoretical conformational analysis can help to understand chemical processes at a molecular level. (author)

  11. On the linear conformal gravitation

    International Nuclear Information System (INIS)

    Pal'chik, M.Ya.; Fradkin, E.S.

    1984-01-01

    Conformal gravitation is analyzed under the assumption that its solution possesses the property of conformal symmetry. This assumption has sense in the case of small distances and only for definite types of matter fields, namely: at special choice of matter fields and their interactions, providing a lack of conformal anomalies; or at definite magnitudes of binding constants, coinciding with the zeroes of the Gell-Mann-Low function. The field equations, of the group-theoretical natura are obtained

  12. Conformance and Deviance

    DEFF Research Database (Denmark)

    Gjerdrum Pedersen, Esben Rahbek; Neergaard, Peter; Thusgaard Pedersen, Janni

    2013-01-01

    This paper analyses how large Danish companies are responding to new governmental regulation which requires them to report on corporate social responsibility (CSR). The paper is based on an analysis of 142 company annual reports required by the new Danish regulation regarding CSR reporting, plus 10...... interviews with first-time reporting companies and six interviews with companies that failed to comply with the new law. It is concluded that coercive pressures from government have an impact on CSR reporting practices. Further, the analysis finds traces of mimetic isomorphism which inspires a homogenisation...... in CSR reporting practices. Finally, it is argued that non-conformance with the new regulatory requirements is not solely about conscious resistance but may also be caused by, for example, lack of awareness, resource limitations, misinterpretations, and practical difficulties....

  13. Reflections on Conformal Spectra

    CERN Multimedia

    CERN. Geneva

    2015-01-01

    We use modular invariance and crossing symmetry of conformal field theory to reveal approximate reflection symmetries in the spectral decompositions of the partition function in two dimensions in the limit of large central charge and of the four-point function in any dimension in the limit of large scaling dimensions Δ0 of external operators. We use these symmetries to motivate universal upper bounds on the spectrum and the operator product expansion coefficients, which we then derive by independent techniques. Some of the bounds for four-point functions are valid for finite Δ0 as well as for large Δ0. We discuss a similar symmetry in a large spacetime dimension limit. Finally, we comment on the analogue of the Cardy formula and sparse light spectrum condition for the four-point function. (based on 1510.08772 with Kim & Ooguri). This seminar will be given via videolink

  14. Determining dark matter properties with a XENONnT/LZ signal and LHC Run 3 monojet searches

    Science.gov (United States)

    Baum, Sebastian; Catena, Riccardo; Conrad, Jan; Freese, Katherine; Krauss, Martin B.

    2018-04-01

    We develop a method to forecast the outcome of the LHC Run 3 based on the hypothetical detection of O (100 ) signal events at XENONnT. Our method relies on a systematic classification of renormalizable single-mediator models for dark matter-quark interactions and is valid for dark matter candidates of spin less than or equal to one. Applying our method to simulated data, we find that at the end of the LHC Run 3 only two mutually exclusive scenarios would be compatible with the detection of O (100 ) signal events at XENONnT. In the first scenario, the energy distribution of the signal events is featureless, as for canonical spin-independent interactions. In this case, if a monojet signal is detected at the LHC, dark matter must have spin 1 /2 and interact with nucleons through a unique velocity-dependent operator. If a monojet signal is not detected, dark matter interacts with nucleons through canonical spin-independent interactions. In a second scenario, the spectral distribution of the signal events exhibits a bump at nonzero recoil energies. In this second case, a monojet signal can be detected at the LHC Run 3; dark matter must have spin 1 /2 and interact with nucleons through a unique momentum-dependent operator. We therefore conclude that the observation of O (100 ) signal events at XENONnT combined with the detection, or the lack of detection, of a monojet signal at the LHC Run 3 would significantly narrow the range of possible dark matter-nucleon interactions. As we argued above, it can also provide key information on the dark matter particle spin.

  15. Conformal boundary loop models

    International Nuclear Information System (INIS)

    Jacobsen, Jesper Lykke; Saleur, Hubert

    2008-01-01

    We study a model of densely packed self-avoiding loops on the annulus, related to the Temperley-Lieb algebra with an extra idempotent boundary generator. Four different weights are given to the loops, depending on their homotopy class and whether they touch the outer rim of the annulus. When the weight of a contractible bulk loop x≡q+q -1 element of (-2,2], this model is conformally invariant for any real weight of the remaining three parameters. We classify the conformal boundary conditions and give exact expressions for the corresponding boundary scaling dimensions. The amplitudes with which the sectors with any prescribed number and types of non-contractible loops appear in the full partition function Z are computed rigorously. Based on this, we write a number of identities involving Z which hold true for any finite size. When the weight of a contractible boundary loop y takes certain discrete values, y r ≡([r+1] q )/([r] q ) with r integer, other identities involving the standard characters K r,s of the Virasoro algebra are established. The connection with Dirichlet and Neumann boundary conditions in the O(n) model is discussed in detail, and new scaling dimensions are derived. When q is a root of unity and y=y r , exact connections with the A m type RSOS model are made. These involve precise relations between the spectra of the loop and RSOS model transfer matrices, valid in finite size. Finally, the results where y=y r are related to the theory of Temperley-Lieb cabling

  16. Logarithmic conformal field theory through nilpotent conformal dimensions

    International Nuclear Information System (INIS)

    Moghimi-Araghi, S.; Rouhani, S.; Saadat, M.

    2001-01-01

    We study logarithmic conformal field theories (LCFTs) through the introduction of nilpotent conformal weights. Using this device, we derive the properties of LCFTs such as the transformation laws, singular vectors and the structure of correlation functions. We discuss the emergence of an extra energy momentum tensor, which is the logarithmic partner of the energy momentum tensor

  17. Replacement between conformity and counter-conformity in consumption decisions.

    Science.gov (United States)

    Chou, Ting-Jui; Chang, En-Chung; Dai, Qi; Wong, Veronica

    2013-02-01

    This study assessed, in a Chinese context, how self-esteem interacts with perceived similarity and uniqueness to yield cognitive dissonance, and whether the dissonance leads to self-reported conformity or counter-conformity behavior. Participants were 408 respondents from 4 major Chinese cities (M age = 33.0 yr., SD = 4.3; 48% men). Self-perceptions of uniqueness, similarity, cognitive dissonance, self-esteem and need to behave in conformity or counter-conformity were measured. A theoretical model was assessed in four situations, relating the ratings of self-esteem and perceived similarity/uniqueness to the way other people at a wedding were dressed, and the resultant cognitive dissonance and conformity/ counter-conformity behavior. Regardless of high or low self-esteem, all participants reported cognitive dissonance when they were told that they were dressed extremely similarly to or extremely differently from the other people attending the wedding. However, the conforming/counter-conforming strategies used by participants to resolve the cognitive dissonance differed. When encountering dissonance induced by the perceived extreme uniqueness of dress, participants with low self-esteem tended to say they would dress next time so as to conform with the way others were dressed, while those with high self-esteem indicated they would continue their counter-conformity in attire. When encountering dissonance induced by the perceived extreme similarity to others, both those with high and low self-esteem tended to say they would dress in an unorthodox manner to surprise other people in the future.

  18. On Associative Conformal Algebras of Linear Growth

    OpenAIRE

    Retakh, Alexander

    2000-01-01

    Lie conformal algebras appear in the theory of vertex algebras. Their relation is similar to that of Lie algebras and their universal enveloping algebras. Associative conformal algebras play a role in conformal representation theory. We introduce the notions of conformal identity and unital associative conformal algebras and classify finitely generated simple unital associative conformal algebras of linear growth. These are precisely the complete algebras of conformal endomorphisms of finite ...

  19. Recent advancements in conformal gravity

    International Nuclear Information System (INIS)

    O’Brien, James G.; Chaykov, Spasen S.; Moss, Robert J.; Dentico, Jeremy; Stulge, Modestas; Stefanski, Brian

    2017-01-01

    In recent years, due to the lack of direct observed evidence of cold dark matter, coupled with the shrinking parameter space to search for new dark matter particles, there has been increased interest in Alternative Gravitational theories. This paper, addresses three recent advances in conformal gravity, a fourth order renormalizable metric theory of gravitation originally formulated by Weyl, and later advanced by Mannheim and Kazanas. The first section of the paper applies conformal gravity to the rotation curves of the LITTLE THINGS survey, extending the total number of rotation curves successfully fit by conformal gravity to well over 200 individual data sets without the need for additional dark matter. Further, in this rotation curve study, we show how MOND and conformal gravity compare for each galaxy in the sample. Second, we look at the original Zwicky problem of applying the virial theorem to the Coma cluster in order to get an estimate for the cluster mass. However, instead of using the standard Newtonian potential, here we use the weak field approximation of conformal gravity. We show that in the conformal case we can get a much smaller mass estimate and thus there is no apparent need to include dark matter. We then show that this calculation is in agreement with the observational data from other well studied clusters. Last, we explore the calculation of the deflection of starlight through conformal gravity, as a first step towards applying conformal gravity to gravitaitonal lensing. (paper)

  20. Conformal invariance in harmonic superspace

    International Nuclear Information System (INIS)

    Galperin, A.; Ivanov, E.; Ogievetsky, V.; Sokatchev, E.

    1985-01-01

    N=2 conformal supersymmetry is realized in harmonic superspace, its peculiarities are analyzed. The coordinate group and analytical prepotentials for N=2 conformal supergravity are found. A new version of the N=2 Einstein supergravity with infinite number of auxiliary fields is suggested. A hypermultiplet without central charges and constraints is used as a compensator

  1. Counselor Identity: Conformity or Distinction?

    Science.gov (United States)

    McLaughlin, Jerry E.; Boettcher, Kathryn

    2009-01-01

    The authors explore 3 debates in other disciplines similar to counseling's identity debate in order to learn about common themes and outcomes. Conformity, distinction, and cohesion emerged as common themes. They conclude that counselors should retain their distinctive, humanistic approach rather than conforming to the dominant, medical approach.

  2. 40 CFR 59.629 - What decisions may EPA make regarding my certificate of conformity?

    Science.gov (United States)

    2010-07-01

    ... my certificate of conformity? 59.629 Section 59.629 Protection of Environment ENVIRONMENTAL... certificate of conformity? (a) If we determine your application is complete and shows that the emission family meets all the requirements of this subpart and the Act, we will issue a certificate of conformity for...

  3. 40 CFR 1051.255 - What decisions may EPA make regarding my certificate of conformity?

    Science.gov (United States)

    2010-07-01

    ... my certificate of conformity? 1051.255 Section 1051.255 Protection of Environment ENVIRONMENTAL... conformity? (a) If we determine your application is complete and shows that the engine family meets all the requirements of this part and the Act, we will issue a certificate of conformity for your engine family for...

  4. 40 CFR 1045.255 - What decisions may EPA make regarding my certificate of conformity?

    Science.gov (United States)

    2010-07-01

    ... my certificate of conformity? 1045.255 Section 1045.255 Protection of Environment ENVIRONMENTAL... certificate of conformity? (a) If we determine your application is complete and shows that the engine family meets all the requirements of this part and the Clean Air Act, we will issue a certificate of conformity...

  5. 40 CFR 1039.255 - What decisions may EPA make regarding my certificate of conformity?

    Science.gov (United States)

    2010-07-01

    ... my certificate of conformity? 1039.255 Section 1039.255 Protection of Environment ENVIRONMENTAL... certificate of conformity? (a) If we determine your application is complete and shows that the engine family meets all the requirements of this part and the Act, we will issue a certificate of conformity for your...

  6. 40 CFR 1048.255 - What decisions may EPA make regarding my certificate of conformity?

    Science.gov (United States)

    2010-07-01

    ... my certificate of conformity? 1048.255 Section 1048.255 Protection of Environment ENVIRONMENTAL... of conformity? (a) If we determine your application is complete and shows that the engine family meets all the requirements of this part and the Act, we will issue a certificate of conformity for your...

  7. 40 CFR 1054.255 - What decisions may EPA make regarding my certificate of conformity?

    Science.gov (United States)

    2010-07-01

    ... my certificate of conformity? 1054.255 Section 1054.255 Protection of Environment ENVIRONMENTAL... regarding my certificate of conformity? (a) If we determine your application is complete and shows that the... of conformity for your emission family for that model year. We may make the approval subject to...

  8. 40 CFR 1060.255 - What decisions may EPA make regarding my certificate of conformity?

    Science.gov (United States)

    2010-07-01

    ... my certificate of conformity? 1060.255 Section 1060.255 Protection of Environment ENVIRONMENTAL... regarding my certificate of conformity? (a) If we determine your application is complete and shows that the... of conformity for your emission family for that production period. We may make the approval subject...

  9. Conformal anomaly actions for dilaton interactions

    Directory of Open Access Journals (Sweden)

    Rose Luigi Delle

    2014-01-01

    Full Text Available We discuss, in conformally invariant field theories such as QCD with massless fermions, a possible link between the perturbative signature of the conformal anomaly, in the form of anomaly poles of the 1-particle irreducible effective action, and its descrip- tion in terms of Wess-Zumino actions with a dilaton. The two descriptions are expected to capture the UV and IR behaviour of the conformal anomaly, in terms of fundamental and effective degrees of freedom respectively, with the dilaton effective state appearing in a nonlinear realization. As in the chiral case, conformal anomalies seem to be related to the appearance of these effective interactions in the 1PI action in all the gauge-invariant sectors of the Standard Model. We show that, as a consequence of the underlying anomalous symmetry, the infinite hierarchy of recurrence relations involving self-interactions of the dilaton is entirely determined only by the first four of them. This relation can be generalized to any even space-time dimension.

  10. Irregular conformal block, spectral curve and flow equations

    International Nuclear Information System (INIS)

    Choi, Sang Kwan; Rim, Chaiho; Zhang, Hong

    2016-01-01

    Irregular conformal block is motivated by the Argyres-Douglas type of N=2 super conformal gauge theory. We investigate the classical/NS limit of irregular conformal block using the spectral curve on a Riemann surface with irregular punctures, which is equivalent to the loop equation of irregular matrix model. The spectral curve is reduced to the second order (Virasoro symmetry, SU(2) for the gauge theory) and third order (W_3 symmetry, SU(3)) differential equations of a polynomial with finite degree. The conformal and W symmetry generate the flow equations in the spectral curve and determine the irregular conformal block, hence the partition function of the Argyres-Douglas theory ala AGT conjecture.

  11. THz time domain spectroscopy of biomolecular conformational modes

    International Nuclear Information System (INIS)

    Markelz, Andrea; Whitmire, Scott; Hillebrecht, Jay; Birge, Robert

    2002-01-01

    We discuss the use of terahertz time domain spectroscopy for studies of conformational flexibility and conformational change in biomolecules. Protein structural dynamics are vital to biological function with protein flexibility affecting enzymatic reaction rates and sensory transduction cycling times. Conformational mode dynamics occur on the picosecond timescale and with the collective vibrational modes associated with these large scale structural motions in the 1-100 cm -1 range. We have performed THz time domain spectroscopy (TTDS) of several biomolecular systems to explore the sensitivity of TTDS to distinguish different molecular species, different mutations within a single species and different conformations of a given biomolecule. We compare the measured absorbances to normal mode calculations and find that the TTDS absorbance reflects the density of normal modes determined by molecular mechanics calculations, and is sensitive to both conformation and mutation. These early studies demonstrate some of the advantages and limitations of using TTDS for the study of biomolecules

  12. Conformal algebra of Riemann surfaces

    International Nuclear Information System (INIS)

    Vafa, C.

    1988-01-01

    It has become clear over the last few years that 2-dimensional conformal field theories are a crucial ingredient of string theory. Conformal field theories correspond to vacuum solutions of strings; or more precisely we know how to compute string spectrum and scattering amplitudes by starting from a formal theory (with a proper value of central charge of the Virasoro algebra). Certain non-linear sigma models do give rise to conformal theories. A lot of progress has been made in the understanding of conformal theories. The author discusses a different view of conformal theories which was motivated by the development of operator formalism on Riemann surfaces. The author discusses an interesting recent work from this point of view

  13. The logarithmic conformal field theories

    International Nuclear Information System (INIS)

    Rahimi Tabar, M.R.; Aghamohammadi, A.; Khorrami, M.

    1997-01-01

    We study the correlation functions of logarithmic conformal field theories. First, assuming conformal invariance, we explicitly calculate two- and three-point functions. This calculation is done for the general case of more than one logarithmic field in a block, and more than one set of logarithmic fields. Then we show that one can regard the logarithmic field as a formal derivative of the ordinary field with respect to its conformal weight. This enables one to calculate any n-point function containing the logarithmic field in terms of ordinary n-point functions. Finally, we calculate the operator product expansion (OPE) coefficients of a logarithmic conformal field theory, and show that these can be obtained from the corresponding coefficients of ordinary conformal theory by a simple derivation. (orig.)

  14. Evolutionary conservation of the polyproline II conformation surrounding intrinsically disordered phosphorylation sites.

    Science.gov (United States)

    Elam, W Austin; Schrank, Travis P; Campagnolo, Andrew J; Hilser, Vincent J

    2013-04-01

    Intrinsically disordered (ID) proteins function in the absence of a unique stable structure and appear to challenge the classic structure-function paradigm. The extent to which ID proteins take advantage of subtle conformational biases to perform functions, and whether signals for such mechanism can be identified in proteome-wide studies is not well understood. Of particular interest is the polyproline II (PII) conformation, suggested to be highly populated in unfolded proteins. We experimentally determine a complete calorimetric propensity scale for the PII conformation. Projection of the scale into representative eukaryotic proteomes reveals significant PII bias in regions coding for ID proteins. Importantly, enrichment of PII in ID proteins, or protein segments, is also captured by other PII scales, indicating that this enrichment is robustly encoded and universally detectable regardless of the method of PII propensity determination. Gene ontology (GO) terms obtained using our PII scale and other scales demonstrate a consensus for molecular functions performed by high PII proteins across the proteome. Perhaps the most striking result of the GO analysis is conserved enrichment (P ontology reveals an enrichment of PII bias near disordered phosphorylation sites that is conserved throughout eukaryotes. Copyright © 2013 The Protein Society.

  15. Conformal solids and holography

    Science.gov (United States)

    Esposito, A.; Garcia-Saenz, S.; Nicolis, A.; Penco, R.

    2017-12-01

    We argue that a SO( d) magnetic monopole in an asymptotically AdS space-time is dual to a d-dimensional strongly coupled system in a solid state. In light of this, it would be remiss of us not to dub such a field configuration solidon. In the presence of mixed boundary conditions, a solidon spontaneously breaks translations (among many other symmetries) and gives rise to Goldstone excitations on the boundary — the phonons of the solid. We derive the quadratic action for the boundary phonons in the probe limit and show that, when the mixed boundary conditions preserve conformal symmetry, the longitudinal and transverse sound speeds are related to each other as expected from effective field theory arguments. We then include backreaction and calculate the free energy of the solidon for a particular choice of mixed boundary conditions, corresponding to a relevant multi-trace deformation of the boundary theory. We find such free energy to be lower than that of thermal AdS. This suggests that our solidon undergoes a solid-to-liquid first order phase transition by melting into a Schwarzschild-AdS black hole as the temperature is raised.

  16. 6d Conformal matter

    International Nuclear Information System (INIS)

    Zotto, Michele Del; Heckman, Jonathan J.; Tomasiello, Alessandro; Vafa, Cumrun

    2015-01-01

    A single M5-brane probing G, an ADE-type singularity, leads to a system which has G×G global symmetry and can be viewed as “bifundamental” (G,G) matter. For the A N series, this leads to the usual notion of bifundamental matter. For the other cases it corresponds to a strongly interacting (1,0) superconformal system in six dimensions. Similarly, an ADE singularity intersecting the Hořava-Witten wall leads to a superconformal matter system with E 8 ×G global symmetry. Using the F-theory realization of these theories, we elucidate the Coulomb/tensor branch of (G,G ′ ) conformal matter. This leads to the notion of fractionalization of an M5-brane on an ADE singularity as well as fractionalization of the intersection point of the ADE singularity with the Hořava-Witten wall. Partial Higgsing of these theories leads to new 6d SCFTs in the infrared, which we also characterize. This generalizes the class of (1,0) theories which can be perturbatively realized by suspended branes in IIA string theory. By reducing on a circle, we arrive at novel duals for 5d affine quiver theories. Introducing many M5-branes leads to large N gravity duals.

  17. Enhanced conformational sampling using enveloping distribution sampling.

    Science.gov (United States)

    Lin, Zhixiong; van Gunsteren, Wilfred F

    2013-10-14

    To lessen the problem of insufficient conformational sampling in biomolecular simulations is still a major challenge in computational biochemistry. In this article, an application of the method of enveloping distribution sampling (EDS) is proposed that addresses this challenge and its sampling efficiency is demonstrated in simulations of a hexa-β-peptide whose conformational equilibrium encompasses two different helical folds, i.e., a right-handed 2.7(10∕12)-helix and a left-handed 3(14)-helix, separated by a high energy barrier. Standard MD simulations of this peptide using the GROMOS 53A6 force field did not reach convergence of the free enthalpy difference between the two helices even after 500 ns of simulation time. The use of soft-core non-bonded interactions in the centre of the peptide did enhance the number of transitions between the helices, but at the same time led to neglect of relevant helical configurations. In the simulations of a two-state EDS reference Hamiltonian that envelops both the physical peptide and the soft-core peptide, sampling of the conformational space of the physical peptide ensures that physically relevant conformations can be visited, and sampling of the conformational space of the soft-core peptide helps to enhance the transitions between the two helices. The EDS simulations sampled many more transitions between the two helices and showed much faster convergence of the relative free enthalpy of the two helices compared with the standard MD simulations with only a slightly larger computational effort to determine optimized EDS parameters. Combined with various methods to smoothen the potential energy surface, the proposed EDS application will be a powerful technique to enhance the sampling efficiency in biomolecular simulations.

  18. The mir-279/996 cluster represses receptor tyrosine kinase signaling to determine cell fates in the Drosophila eye.

    Science.gov (United States)

    Duan, Hong; de Navas, Luis F; Hu, Fuqu; Sun, Kailiang; Mavromatakis, Yannis E; Viets, Kayla; Zhou, Cyrus; Kavaler, Joshua; Johnston, Robert J; Tomlinson, Andrew; Lai, Eric C

    2018-04-09

    Photoreceptors in the crystalline Drosophila eye are recruited by receptor tyrosine kinase (RTK)/Ras signaling mediated by Epidermal growth factor receptor (EGFR) and the Sevenless (Sev) receptor. Analyses of an allelic deletion series of the mir-279/996 locus, along with a panel of modified genomic rescue transgenes, show that Drosophila eye patterning depends on both miRNAs. Transcriptional reporter and activity sensor transgenes reveal expression and function of miR-279/996 in non-neural cells of the developing eye. Moreover, mir-279/996 mutants exhibit substantial numbers of ectopic photoreceptors, particularly of R7, and cone cell loss. These miRNAs restrict RTK signaling in the eye, since mir-279/996 nulls are dominantly suppressed by positive components of the EGFR pathway and enhanced by heterozygosity for an EGFR repressor. miR-279/996 limit photoreceptor recruitment by targeting multiple positive RTK/Ras signaling components that promote photoreceptor/R7 specification. Strikingly, deletion of mir-279/996 sufficiently derepresses RTK/Ras signaling so as to rescue a population of R7 cells in R7-specific RTK null mutants boss and sev , which otherwise completely lack this cell fate. Altogether, we reveal a rare setting of developmental cell specification that involves substantial miRNA control. © 2018. Published by The Company of Biologists Ltd.

  19. Kinetics in Signal Transduction Pathways Involving Promiscuous Oligomerizing Receptors Can Be Determined by Receptor Specificity : Apoptosis Induction by TRAIL

    NARCIS (Netherlands)

    Szegezdi, Eva; van der Sloot, Almer M.; Mahalingam, Devalingam; O'Leary, Lynda; Cool, Robbert H.; Munoz, Ines G.; Montoya, Guillermo; Quax, Wim J.; de Jong, Steven; Samali, Afshin; Serrano, Luis

    Here we show by computer modeling that kinetics and outcome of signal transduction in case of hetero-oligomerizing receptors of a promiscuous ligand largely depend on the relative amounts of its receptors. Promiscuous ligands can trigger the formation of nonproductive receptor complexes, which slows

  20. Towards conformal loop quantum gravity

    International Nuclear Information System (INIS)

    Wang, Charles H-T

    2006-01-01

    A discussion is given of recent developments in canonical gravity that assimilates the conformal analysis of gravitational degrees of freedom. The work is motivated by the problem of time in quantum gravity and is carried out at the metric and the triad levels. At the metric level, it is shown that by extending the Arnowitt-Deser-Misner (ADM) phase space of general relativity (GR), a conformal form of geometrodynamics can be constructed. In addition to the Hamiltonian and Diffeomorphism constraints, an extra first class constraint is introduced to generate conformal transformations. This phase space consists of York's mean extrinsic curvature time, conformal three-metric and their momenta. At the triad level, the phase space of GR is further enlarged by incorporating spin-gauge as well as conformal symmetries. This leads to a canonical formulation of GR using a new set of real spin connection variables. The resulting gravitational constraints are first class, consisting of the Hamiltonian constraint and the canonical generators for spin-gauge and conformorphism transformations. The formulation has a remarkable feature of being parameter-free. Indeed, it is shown that a conformal parameter of the Barbero-Immirzi type can be absorbed by the conformal symmetry of the extended phase space. This gives rise to an alternative approach to loop quantum gravity that addresses both the conceptual problem of time and the technical problem of functional calculus in quantum gravity

  1. Benchmarking Commercial Conformer Ensemble Generators.

    Science.gov (United States)

    Friedrich, Nils-Ole; de Bruyn Kops, Christina; Flachsenberg, Florian; Sommer, Kai; Rarey, Matthias; Kirchmair, Johannes

    2017-11-27

    We assess and compare the performance of eight commercial conformer ensemble generators (ConfGen, ConfGenX, cxcalc, iCon, MOE LowModeMD, MOE Stochastic, MOE Conformation Import, and OMEGA) and one leading free algorithm, the distance geometry algorithm implemented in RDKit. The comparative study is based on a new version of the Platinum Diverse Dataset, a high-quality benchmarking dataset of 2859 protein-bound ligand conformations extracted from the PDB. Differences in the performance of commercial algorithms are much smaller than those observed for free algorithms in our previous study (J. Chem. Inf. 2017, 57, 529-539). For commercial algorithms, the median minimum root-mean-square deviations measured between protein-bound ligand conformations and ensembles of a maximum of 250 conformers are between 0.46 and 0.61 Å. Commercial conformer ensemble generators are characterized by their high robustness, with at least 99% of all input molecules successfully processed and few or even no substantial geometrical errors detectable in their output conformations. The RDKit distance geometry algorithm (with minimization enabled) appears to be a good free alternative since its performance is comparable to that of the midranked commercial algorithms. Based on a statistical analysis, we elaborate on which algorithms to use and how to parametrize them for best performance in different application scenarios.

  2. Conformal invariance in harmonic superspace

    International Nuclear Information System (INIS)

    Galperin, A.; Ivanov, E.; Ogievetsky, V.; Sokatchev, E.

    1987-01-01

    In the present paper we show how the N = 2 superconformal group is realised in harmonic superspace and examine conformal invariance of N = 2 off-shell theories. We believe that the example of N = O self-dual Yang-Mills equations can serve as an instructive introduction to the subject of harmonic superspace and this is examined. The rigid N = 2 conformal supersymmetry and its local version, i.e. N = 2 conformal supergravity is also discussed. The paper is a contribution to the book commemorating the sixtieth birthday of E.S. Fradkin. (author)

  3. Two dimensional infinite conformal symmetry

    International Nuclear Information System (INIS)

    Mohanta, N.N.; Tripathy, K.C.

    1993-01-01

    The invariant discontinuous (discrete) conformal transformation groups, namely the Kleinian and Fuchsian groups Gamma (with an arbitrary signature) of H (the Poincare upper half-plane l) and the unit disc Delta are explicitly constructed from the fundamental domain D. The Riemann surface with signatures of Gamma and conformally invariant automorphic forms (functions) with Peterson scalar product are discussed. The functor, where the category of complex Hilbert spaces spanned by the space of cusp forms constitutes the two dimensional conformal field theory. (Author) 7 refs

  4. Harmony of spinning conformal blocks

    Energy Technology Data Exchange (ETDEWEB)

    Schomerus, Volker [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany). Theory Group; Sobko, Evgeny [Stockholm Univ. (Sweden); Nordita, Stockholm (Sweden); Isachenkov, Mikhail [Weizmann Institute of Science, Rehovoth (Israel). Dept. of Particle Physics and Astrophysics

    2016-12-07

    Conformal blocks for correlation functions of tensor operators play an increasingly important role for the conformal bootstrap programme. We develop a universal approach to such spinning blocks through the harmonic analysis of certain bundles over a coset of the conformal group. The resulting Casimir equations are given by a matrix version of the Calogero-Sutherland Hamiltonian that describes the scattering of interacting spinning particles in a 1-dimensional external potential. The approach is illustrated in several examples including fermionic seed blocks in 3D CFT where they take a very simple form.

  5. Harmony of spinning conformal blocks

    Energy Technology Data Exchange (ETDEWEB)

    Schomerus, Volker [DESY Hamburg, Theory Group,Notkestraße 85, 22607 Hamburg (Germany); Sobko, Evgeny [Nordita and Stockholm University,Roslagstullsbacken 23, SE-106 91 Stockholm (Sweden); Isachenkov, Mikhail [Department of Particle Physics and Astrophysics, Weizmann Institute of Science,Rehovot 7610001 (Israel)

    2017-03-15

    Conformal blocks for correlation functions of tensor operators play an increasingly important role for the conformal bootstrap programme. We develop a universal approach to such spinning blocks through the harmonic analysis of certain bundles over a coset of the conformal group. The resulting Casimir equations are given by a matrix version of the Calogero-Sutherland Hamiltonian that describes the scattering of interacting spinning particles in a 1-dimensional external potential. The approach is illustrated in several examples including fermionic seed blocks in 3D CFT where they take a very simple form.

  6. Determination of relative configurations and conformations of oxindole alkaloids from Uncaria guianensis by NMR; Determinacao por RMN das configuracoes relativas e conformacoes de alcaloides oxindolicos isolados de Uncaria guianensis

    Energy Technology Data Exchange (ETDEWEB)

    Carbonezi, Carlos Alberto; Hamerski, Lidilhone; Flausino Junior, Otavio Aparecido; Furlan, Maysa; Bolzani, Vanderlan da Silva [UNESP, Araraquara, SP (Brazil). Inst. de Quimica]. E-mail: bolzaniv@iq.unesp.br; Young, Maria Claudia Marx [Instituto de Botanica, Sao Paulo, SP (Brazil). Secao de Fisiologia e Bioquimica de Plantas

    2004-12-01

    Phytochemical studies with leaves of Uncaria guianensis resulted in the isolation of the oxindole alkaloids isomitraphylline (1), 3-isoajmalicine (2) mitraphylline (3), and isomitraphylinic acid (4). Structural assignments of these alkaloids, including relative configurations and conformations, were performed through spectral data and physical properties. 1D and 2D homonuclear and heteronuclear NMR spectroscopy was a valuable tool for the establishment of the relative stereochemistry of those compounds. (author)

  7. Mass generation within conformal invariant theories

    International Nuclear Information System (INIS)

    Flato, M.; Guenin, M.

    1981-01-01

    The massless Yang-Mills theory is strongly conformally invariant and renormalizable; however, when masses are introduced the theory becomes nonrenormalizable and weakly conformally invariant. Conditions which recover strong conformal invariance are discussed in the letter. (author)

  8. Diagonal Limit for Conformal Blocks in d Dimensions

    CERN Document Server

    Hogervorst, Matthijs; Rychkov, Slava

    2013-01-01

    Conformal blocks in any number of dimensions depend on two variables z, zbar. Here we study their restrictions to the special "diagonal" kinematics z = zbar, previously found useful as a starting point for the conformal bootstrap analysis. We show that conformal blocks on the diagonal satisfy ordinary differential equations, third-order for spin zero and fourth-order for the general case. These ODEs determine the blocks uniquely and lead to an efficient numerical evaluation algorithm. For equal external operator dimensions, we find closed-form solutions in terms of finite sums of 3F2 functions.

  9. A test of conformal invariance: Correlation functions on a disk

    International Nuclear Information System (INIS)

    Badke, R.; Rittenberg, V.; Ruegg, H.

    1985-06-01

    Using conformal invariance one can derive the correlation functions of a disk from those in the half-plane. The correlation function in the half-plane is determined by the 'small' conformal invariance up to an unknown function of one variable. By measuring through the Monte Carlo method the correlation function for two different configurations, the unknown function can be eliminated and one obtains a test of conformal invariance. It is shown that the Ising and the three state Potts model pass the test for very small lattices. (orig.)

  10. Prescribed curvature tensor in locally conformally flat manifolds

    Science.gov (United States)

    Pina, Romildo; Pieterzack, Mauricio

    2018-01-01

    A global existence theorem for the prescribed curvature tensor problem in locally conformally flat manifolds is proved for a special class of tensors R. Necessary and sufficient conditions for the existence of a metric g ¯ , conformal to Euclidean g, are determined such that R ¯ = R, where R ¯ is the Riemannian curvature tensor of the metric g ¯ . The solution to this problem is given explicitly for special cases of the tensor R, including the case where the metric g ¯ is complete on Rn. Similar problems are considered for locally conformally flat manifolds.

  11. Low-Mode Conformational Search Method with Semiempirical Quantum Mechanical Calculations: Application to Enantioselective Organocatalysis.

    Science.gov (United States)

    Kamachi, Takashi; Yoshizawa, Kazunari

    2016-02-22

    A conformational search program for finding low-energy conformations of large noncovalent complexes has been developed. A quantitatively reliable semiempirical quantum mechanical PM6-DH+ method, which is able to accurately describe noncovalent interactions at a low computational cost, was employed in contrast to conventional conformational search programs in which molecular mechanical methods are usually adopted. Our approach is based on the low-mode method whereby an initial structure is perturbed along one of its low-mode eigenvectors to generate new conformations. This method was applied to determine the most stable conformation of transition state for enantioselective alkylation by the Maruoka and cinchona alkaloid catalysts and Hantzsch ester hydrogenation of imines by chiral phosphoric acid. Besides successfully reproducing the previously reported most stable DFT conformations, the conformational search with the semiempirical quantum mechanical calculations newly discovered a more stable conformation at a low computational cost.

  12. Determination of the influence of asymmetry of the electric field distribution in gaseous proportional counters on their signal amplitude

    International Nuclear Information System (INIS)

    Jagusztyn, W.

    1976-01-01

    A method is described of establishing the influence of the asymmetry of the electric field distribution in gaseous proportional counters on the amplitude of their voltage signal. A numerical evaluation of this effect demands performing calculations of the electric field in the vicinity of the anode. Using the described method of numerical solution of the Laplace equation in polar coordinates with logarythmically scaled radial dimension, it is possible to achieve the required accuracy. In the calculations of differences in amplitudes of voltage signals, for chosen trajektories of electrons liberated in the process of primary ionization, changes in the gaseous amplification factors and drift velocities of positive ions are taken into account. Experimental results prove the validity of presented theory. The results obtained are accurate enough to be applied to the design of proportional counters of non-cylindrical geometries. (author)

  13. A computerized traffic control algorithm to determine optimal traffic signal settings. Ph.D. Thesis - Toledo Univ.

    Science.gov (United States)

    Seldner, K.

    1977-01-01

    An algorithm was developed to optimally control the traffic signals at each intersection using a discrete time traffic model applicable to heavy or peak traffic. Off line optimization procedures were applied to compute the cycle splits required to minimize the lengths of the vehicle queues and delay at each intersection. The method was applied to an extensive traffic network in Toledo, Ohio. Results obtained with the derived optimal settings are compared with the control settings presently in use.

  14. Rational design of a conformation-switchable Ca2+- and Tb3+-binding protein without the use of multiple coupled metal-binding sites.

    Science.gov (United States)

    Li, Shunyi; Yang, Wei; Maniccia, Anna W; Barrow, Doyle; Tjong, Harianto; Zhou, Huan-Xiang; Yang, Jenny J

    2008-10-01

    Ca2+, as a messenger of signal transduction, regulates numerous target molecules via Ca2+-induced conformational changes. Investigation into the determinants for Ca2+-induced conformational change is often impeded by cooperativity between multiple metal-binding sites or protein oligomerization in naturally occurring proteins. To dissect the relative contributions of key determinants for Ca2+-dependent conformational changes, we report the design of a single-site Ca2+-binding protein (CD2.trigger) created by altering charged residues at an electrostatically sensitive location on the surface of the host protein rat Cluster of Differentiation 2 (CD2).CD2.trigger binds to Tb3+ and Ca2+ with dissociation constants of 0.3 +/- 0.1 and 90 +/- 25 microM, respectively. This protein is largely unfolded in the absence of metal ions at physiological pH, but Tb3+ or Ca2+ binding results in folding of the native-like conformation. Neutralization of the charged coordination residues, either by mutation or protonation, similarly induces folding of the protein. The control of a major conformational change by a single Ca2+ ion, achieved on a protein designed without reliance on sequence similarity to known Ca2+-dependent proteins and coupled metal-binding sites, represents an important step in the design of trigger proteins.

  15. IGF-1 Receptor and adhesion signaling: an important axis in determining cancer cell phenotype and therapy resistance.

    Directory of Open Access Journals (Sweden)

    Orla T Cox

    2015-07-01

    Full Text Available IGF-1R expression and activation levels generally cannot be correlated in cancer cells, suggesting that cellular proteins may modulate IGF-1R activity. Strong candidates for such modulation are found in cell-matrix and cell-cell adhesion signaling complexes. Activated IGF-1R is present at focal adhesions, where it can stabilize β1 integrin and participate in signaling complexes that promote invasiveness associated with epithelial mesenchymal transition (EMT, and resistance to therapy. Whether IGF-1R contributes to EMT or to non-invasive tumor growth may be strongly influenced by the degree of ECM engagement and the presence or absence of key proteins in IGF-1R-cell adhesion complexes. One such protein is PDLIM2, which promotes both cell polarization and EMT by regulating the stability of transcription factors including NFκB, STATs and beta catenin. PDLIM2 exhibits tumor suppressor activity, but is also highly expressed in certain invasive cancers. It is likely that distinct adhesion complex proteins modulate IGF-1R signaling during cancer progression or adaptive responses to therapy. Thus, identifying the key modulators will be important for developing effective therapeutic strategies and predictive biomarkers.

  16. Implications of conformal invariance in momentum space

    Science.gov (United States)

    Bzowski, Adam; McFadden, Paul; Skenderis, Kostas

    2014-03-01

    We present a comprehensive analysis of the implications of conformal invariance for 3-point functions of the stress-energy tensor, conserved currents and scalar operators in general dimension and in momentum space. Our starting point is a novel and very effective decomposition of tensor correlators which reduces their computation to that of a number of scalar form factors. For example, the most general 3-point function of a conserved and traceless stress-energy tensor is determined by only five form factors. Dilatations and special conformal Ward identities then impose additional conditions on these form factors. The special conformal Ward identities become a set of first and second order differential equations, whose general solution is given in terms of integrals involving a product of three Bessel functions (`triple- K integrals'). All in all, the correlators are completely determined up to a number of constants, in agreement with well-known position space results. In odd dimensions 3-point functions are finite without renormalisation while in even dimensions non-trivial renormalisation in required. In this paper we restrict ourselves to odd dimensions. A comprehensive analysis of renormalisation will be discussed elsewhere. This paper contains two parts that can be read independently of each other. In the first part, we explain the method that leads to the solution for the correlators in terms of triple- K integrals while the second part contains a self-contained presentation of all results. Readers interested only in results may directly consult the second part of the paper.

  17. Moduli spaces of unitary conformal field theories

    International Nuclear Information System (INIS)

    Wendland, K.

    2000-08-01

    We investigate various features of moduli spaces of unitary conformal field theories. A geometric characterization of rational toroidal conformal field theories in arbitrary dimensions is presented and discussed in relation to singular tori and those with complex multiplication. We study the moduli space M 2 of unitary two-dimensional conformal field theories with central charge c = 2. All the 26 non-exceptional non-isolated irreducible components of M 2 are constructed that may be obtained by an orbifold procedure from toroidal theories. The parameter spaces and partition functions are calculated explicitly. All multicritical points and lines are determined, such that all but three of these 26 components are directly or indirectly connected to the space of toroidal theories in M 2 . Relating our results to those by Dixon, Ginsparg, Harvey on the classification of c = 3/2 superconformal field theories, we give geometric interpretations to all non-isolated orbifolds discussed by them and correct their statements on multicritical points within the moduli space of c = 3/2 superconformal field theories. In the main part of this work, we investigate the moduli space M of N = (4, 4) superconformal field theories with central charge c = 6. After a slight emendation of its global description we give generic partition functions for models contained in M. We explicitly determine the locations of various known models in the component of M associated to K3 surfaces

  18. Logarithmic conformal field theory

    Science.gov (United States)

    Gainutdinov, Azat; Ridout, David; Runkel, Ingo

    2013-12-01

    Conformal field theory (CFT) has proven to be one of the richest and deepest subjects of modern theoretical and mathematical physics research, especially as regards statistical mechanics and string theory. It has also stimulated an enormous amount of activity in mathematics, shaping and building bridges between seemingly disparate fields through the study of vertex operator algebras, a (partial) axiomatisation of a chiral CFT. One can add to this that the successes of CFT, particularly when applied to statistical lattice models, have also served as an inspiration for mathematicians to develop entirely new fields: the Schramm-Loewner evolution and Smirnov's discrete complex analysis being notable examples. When the energy operator fails to be diagonalisable on the quantum state space, the CFT is said to be logarithmic. Consequently, a logarithmic CFT is one whose quantum space of states is constructed from a collection of representations which includes reducible but indecomposable ones. This qualifier arises because of the consequence that certain correlation functions will possess logarithmic singularities, something that contrasts with the familiar case of power law singularities. While such logarithmic singularities and reducible representations were noted by Rozansky and Saleur in their study of the U (1|1) Wess-Zumino-Witten model in 1992, the link between the non-diagonalisability of the energy operator and logarithmic singularities in correlators is usually ascribed to Gurarie's 1993 article (his paper also contains the first usage of the term 'logarithmic conformal field theory'). The class of CFTs that were under control at this time was quite small. In particular, an enormous amount of work from the statistical mechanics and string theory communities had produced a fairly detailed understanding of the (so-called) rational CFTs. However, physicists from both camps were well aware that applications from many diverse fields required significantly more

  19. Higher-derivative generalization of conformal mechanics

    Science.gov (United States)

    Baranovsky, Oleg

    2017-08-01

    Higher-derivative analogs of multidimensional conformal particle and many-body conformal mechanics are constructed. Their Newton-Hooke counterparts are derived by applying appropriate coordinate transformations.

  20. Naturality in conformal field theory

    International Nuclear Information System (INIS)

    Moore, G.; Seiberg, N.

    1989-01-01

    We discuss constraints on the operator product coefficients in diagonal and nondiagonal rational conformal field theories. Nondiagonal modular invariants always arise from automorphisms of the fusion rule algebra or from extensions of the chiral algebra. Moreover, when the chiral algebra has been maximally extended a strong form of the naturality principle of field theory can be proven for rational conformal field theory: operator product coefficients vanish if and only if the corresponding fusion rules vanish; that is, if and only if the vanishing can be understood in terms of a symmetry. We illustrate these ideas with several examples. We also generalize our ideas about rational conformal field theories to a larger class of theories: 'quasi-rational conformal field theories' and we explore some of their properties. (orig.)

  1. Steady states in conformal theories

    CERN Multimedia

    CERN. Geneva

    2015-01-01

    A novel conjecture regarding the steady state behavior of conformal field theories placed between two heat baths will be presented. Some verification of the conjecture will be provided in the context of fluid dynamics and holography.

  2. National Automated Conformity Inspection Process -

    Data.gov (United States)

    Department of Transportation — The National Automated Conformity Inspection Process (NACIP) Application is intended to expedite the workflow process as it pertains to the FAA Form 81 0-10 Request...

  3. Aspect of the conformal invariance

    International Nuclear Information System (INIS)

    Bauer, M.

    1990-11-01

    This thesis is about the study of several physical and mathematical aspects of critical phenomena at two dimensions. These phenomena have remarkable symmetry properties in the coordonnates changes keeping the angles. They are named conformal theories

  4. Some Progress in Conformal Geometry

    Directory of Open Access Journals (Sweden)

    Sun-Yung A. Chang

    2007-12-01

    Full Text Available This is a survey paper of our current research on the theory of partial differential equations in conformal geometry. Our intention is to describe some of our current works in a rather brief and expository fashion. We are not giving a comprehensive survey on the subject and references cited here are not intended to be complete. We introduce a bubble tree structure to study the degeneration of a class of Yamabe metrics on Bach flat manifolds satisfying some global conformal bounds on compact manifolds of dimension 4. As applications, we establish a gap theorem, a finiteness theorem for diffeomorphism type for this class, and diameter bound of the $sigma_2$-metrics in a class of conformal 4-manifolds. For conformally compact Einstein metrics we introduce an eigenfunction compactification. As a consequence we obtain some topological constraints in terms of renormalized volumes.

  5. Conformity Adequacy Review: Region 5

    Science.gov (United States)

    Resources are for air quality and transportation government and community leaders. Information on the conformity SIP adequacy/inadequacy of state implementation plans (SIPs) in EPA Region 5 (IL, IN, MI, OH, WI) is provided here.

  6. Inverse bootstrapping conformal field theories

    Science.gov (United States)

    Li, Wenliang

    2018-01-01

    We propose a novel approach to study conformal field theories (CFTs) in general dimensions. In the conformal bootstrap program, one usually searches for consistent CFT data that satisfy crossing symmetry. In the new method, we reverse the logic and interpret manifestly crossing-symmetric functions as generating functions of conformal data. Physical CFTs can be obtained by scanning the space of crossing-symmetric functions. By truncating the fusion rules, we are able to concentrate on the low-lying operators and derive some approximate relations for their conformal data. It turns out that the free scalar theory, the 2d minimal model CFTs, the ϕ 4 Wilson-Fisher CFT, the Lee-Yang CFTs and the Ising CFTs are consistent with the universal relations from the minimal fusion rule ϕ 1 × ϕ 1 = I + ϕ 2 + T , where ϕ 1 , ϕ 2 are scalar operators, I is the identity operator and T is the stress tensor.

  7. Covariant Conformal Decomposition of Einstein Equations

    Science.gov (United States)

    Gourgoulhon, E.; Novak, J.

    It has been shown1,2 that the usual 3+1 form of Einstein's equations may be ill-posed. This result has been previously observed in numerical simulations3,4. We present a 3+1 type formalism inspired by these works to decompose Einstein's equations. This decomposition is motivated by the aim of stable numerical implementation and resolution of the equations. We introduce the conformal 3-``metric'' (scaled by the determinant of the usual 3-metric) which is a tensor density of weight -2/3. The Einstein equations are then derived in terms of this ``metric'', of the conformal extrinsic curvature and in terms of the associated derivative. We also introduce a flat 3-metric (the asymptotic metric for isolated systems) and the associated derivative. Finally, the generalized Dirac gauge (introduced by Smarr and York5) is used in this formalism and some examples of formulation of Einstein's equations are shown.

  8. Conformal radiotherapy: principles and classification

    International Nuclear Information System (INIS)

    Rosenwald, J.C.; Gaboriaud, G.; Pontvert, D.

    1999-01-01

    'Conformal radiotherapy' is the name fixed by usage and given to a new form of radiotherapy resulting from the technological improvements observed during the last ten years. While this terminology is now widely used, no precise definition can be found in the literature. Conformal radiotherapy refers to an approach in which the dose distribution is more closely 'conformed' or adapted to the actual shape of the target volume. However, the achievement of a consensus on a more specific definition is hampered by various difficulties, namely in characterizing the degree of 'conformality'. We have therefore suggested a classification scheme be established on the basis of the tools and the procedures actually used for all steps of the process, i.e., from prescription to treatment completion. Our classification consists of four levels: schematically, at level 0, there is no conformation (rectangular fields); at level 1, a simple conformation takes place, on the basis of conventional 2D imaging; at level 2, a 3D reconstruction of the structures is used for a more accurate conformation; and level 3 includes research and advanced dynamic techniques. We have used our personal experience, contacts with colleagues and data from the literature to analyze all the steps of the planning process, and to define the tools and procedures relevant to a given level. The corresponding tables have been discussed and approved at the European level within the Dynarad concerted action. It is proposed that the term 'conformal radiotherapy' be restricted to procedures where all steps are at least at level 2. (author)

  9. Conformal Cosmology and Supernova Data

    OpenAIRE

    Behnke, Danilo; Blaschke, David; Pervushin, Victor; Proskurin, Denis

    2000-01-01

    We define the cosmological parameters $H_{c,0}$, $\\Omega_{m,c}$ and $\\Omega_{\\Lambda, c}$ within the Conformal Cosmology as obtained by the homogeneous approximation to the conformal-invariant generalization of Einstein's General Relativity theory. We present the definitions of the age of the universe and of the luminosity distance in the context of this approach. A possible explanation of the recent data from distant supernovae Ia without a cosmological constant is presented.

  10. Scalar perturbations and conformal transformation

    International Nuclear Information System (INIS)

    Fabris, J.C.; Tossa, J.

    1995-11-01

    The non-minimal coupling of gravity to a scalar field can be transformed into a minimal coupling through a conformal transformation. We show how to connect the results of a perturbation calculation, performed around a Friedman-Robertson-Walker background solution, before and after the conformal transformation. We work in the synchronous gauge, but we discuss the implications of employing other frames. (author). 16 refs

  11. Determination of the off-shell Higgs boson signal strength in the high-mass $ZZ$ and $WW$ final states with the ATLAS detector

    CERN Document Server

    Aad, Georges; Abdallah, Jalal; Abdinov, Ovsat; Aben, Rosemarie; Abolins, Maris; AbouZeid, Ossama; Abramowicz, Halina; Abreu, Henso; Abreu, Ricardo; Abulaiti, Yiming; Acharya, Bobby Samir; Adamczyk, Leszek; Adams, David; Adelman, Jahred; Adomeit, Stefanie; Adye, Tim; Affolder, Tony; Agatonovic-Jovin, Tatjana; Aguilar-Saavedra, Juan Antonio; Agustoni, Marco; Ahlen, Steven; Ahmadov, Faig; Aielli, Giulio; Akerstedt, Henrik; Åkesson, Torsten Paul Ake; Akimoto, Ginga; Akimov, Andrei; Alberghi, Gian Luigi; Albert, Justin; Albrand, Solveig; Alconada Verzini, Maria Josefina; Aleksa, Martin; Aleksandrov, Igor; Alexa, Calin; Alexander, Gideon; Alexopoulos, Theodoros; Alhroob, Muhammad; Alimonti, Gianluca; Alio, Lion; Alison, John; Allbrooke, Benedict; Allport, Phillip; Aloisio, Alberto; Alonso, Alejandro; Alonso, Francisco; Alpigiani, Cristiano; Altheimer, Andrew David; Alvarez Gonzalez, Barbara; Άlvarez Piqueras, Damián; Alviggi, Mariagrazia; Amako, Katsuya; Amaral Coutinho, Yara; Amelung, Christoph; Amidei, Dante; Amor Dos Santos, Susana Patricia; Amorim, Antonio; Amoroso, Simone; Amram, Nir; Amundsen, Glenn; Anastopoulos, Christos; Ancu, Lucian Stefan; Andari, Nansi; Andeen, Timothy; Anders, Christoph Falk; Anders, Gabriel; Anderson, Kelby; Andreazza, Attilio; Andrei, George Victor; Angelidakis, Stylianos; Angelozzi, Ivan; Anger, Philipp; Angerami, Aaron; Anghinolfi, Francis; Anisenkov, Alexey; Anjos, Nuno; Annovi, Alberto; Antonelli, Mario; Antonov, Alexey; Antos, Jaroslav; Anulli, Fabio; Aoki, Masato; Aperio Bella, Ludovica; Arabidze, Giorgi; Arai, Yasuo; Araque, Juan Pedro; Arce, Ayana; Arduh, Francisco Anuar; Arguin, Jean-Francois; Argyropoulos, Spyridon; Arik, Metin; Armbruster, Aaron James; Arnaez, Olivier; Arnal, Vanessa; Arnold, Hannah; Arratia, Miguel; Arslan, Ozan; Artamonov, Andrei; Artoni, Giacomo; Asai, Shoji; Asbah, Nedaa; Ashkenazi, Adi; Åsman, Barbro; Asquith, Lily; Assamagan, Ketevi; Astalos, Robert; Atkinson, Markus; Atlay, Naim Bora; Auerbach, Benjamin; Augsten, Kamil; Aurousseau, Mathieu; Avolio, Giuseppe; Axen, Bradley; Ayoub, Mohamad Kassem; Azuelos, Georges; Baak, Max; Baas, Alessandra; Bacci, Cesare; Bachacou, Henri; Bachas, Konstantinos; Backes, Moritz; Backhaus, Malte; Badescu, Elisabeta; Bagiacchi, Paolo; Bagnaia, Paolo; Bai, Yu; Bain, Travis; Baines, John; Baker, Oliver Keith; Balek, Petr; Balestri, Thomas; Balli, Fabrice; Banas, Elzbieta; Banerjee, Swagato; Bannoura, Arwa A E; Bansil, Hardeep Singh; Barak, Liron; Baranov, Sergei; Barberio, Elisabetta Luigia; Barberis, Dario; Barbero, Marlon; Barillari, Teresa; Barisonzi, Marcello; Barklow, Timothy; Barlow, Nick; Barnes, Sarah Louise; Barnett, Bruce; Barnett, Michael; Barnovska, Zuzana; Baroncelli, Antonio; Barone, Gaetano; Barr, Alan; Barreiro, Fernando; Barreiro Guimarães da Costa, João; Bartoldus, Rainer; Barton, Adam Edward; Bartos, Pavol; Bassalat, Ahmed; Basye, Austin; Bates, Richard; Batista, Santiago Juan; Batley, Richard; Battaglia, Marco; Bauce, Matteo; Bauer, Florian; Bawa, Harinder Singh; Beacham, James Baker; Beattie, Michael David; Beau, Tristan; Beauchemin, Pierre-Hugues; Beccherle, Roberto; Bechtle, Philip; Beck, Hans Peter; Becker, Anne Kathrin; Becker, Maurice; Becker, Sebastian; Beckingham, Matthew; Becot, Cyril; Beddall, Andrew; Beddall, Ayda; Bednyakov, Vadim; Bee, Christopher; Beemster, Lars; Beermann, Thomas; Begel, Michael; Behr, Katharina; Belanger-Champagne, Camille; Bell, Paul; Bell, William; Bella, Gideon; Bellagamba, Lorenzo; Bellerive, Alain; Bellomo, Massimiliano; Belotskiy, Konstantin; Beltramello, Olga; Benary, Odette; Benchekroun, Driss; Bender, Michael; Bendtz, Katarina; Benekos, Nektarios; Benhammou, Yan; Benhar Noccioli, Eleonora; Benitez Garcia, Jorge-Armando; Benjamin, Douglas; Bensinger, James; Bentvelsen, Stan; Beresford, Lydia; Beretta, Matteo; Berge, David; Bergeaas Kuutmann, Elin; Berger, Nicolas; Berghaus, Frank; Beringer, Jürg; Bernard, Clare; Bernard, Nathan Rogers; Bernius, Catrin; Bernlochner, Florian Urs; Berry, Tracey; Berta, Peter; Bertella, Claudia; Bertoli, Gabriele; Bertolucci, Federico; Bertsche, Carolyn; Bertsche, David; Besana, Maria Ilaria; Besjes, Geert-Jan; Bessidskaia Bylund, Olga; Bessner, Martin Florian; Besson, Nathalie; Betancourt, Christopher; Bethke, Siegfried; Bevan, Adrian John; Bhimji, Wahid; Bianchi, Riccardo-Maria; Bianchini, Louis; Bianco, Michele; Biebel, Otmar; Bieniek, Stephen Paul; Biglietti, Michela; Bilbao De Mendizabal, Javier; Bilokon, Halina; Bindi, Marcello; Binet, Sebastien; Bingul, Ahmet; Bini, Cesare; Black, Curtis; Black, James; Black, Kevin; Blackburn, Daniel; Blair, Robert; Blanchard, Jean-Baptiste; Blanco, Jacobo Ezequiel; Blazek, Tomas; Bloch, Ingo; Blocker, Craig; Blum, Walter; Blumenschein, Ulrike; Bobbink, Gerjan; Bobrovnikov, Victor; Bocchetta, Simona Serena; Bocci, Andrea; Bock, Christopher; Boehler, Michael; Bogaerts, Joannes Andreas; Bogdanchikov, Alexander; Bohm, Christian; Boisvert, Veronique; Bold, Tomasz; Boldea, Venera; Boldyrev, Alexey; Bomben, Marco; Bona, Marcella; Boonekamp, Maarten; Borisov, Anatoly; Borissov, Guennadi; Borroni, Sara; Bortfeldt, Jonathan; Bortolotto, Valerio; Bos, Kors; Boscherini, Davide; Bosman, Martine; Boudreau, Joseph; Bouffard, Julian; Bouhova-Thacker, Evelina Vassileva; Boumediene, Djamel Eddine; Bourdarios, Claire; Bousson, Nicolas; Boutouil, Sara; Boveia, Antonio; Boyd, James; Boyko, Igor; Bozic, Ivan; Bracinik, Juraj; Brandt, Andrew; Brandt, Gerhard; Brandt, Oleg; Bratzler, Uwe; Brau, Benjamin; Brau, James; Braun, Helmut; Brazzale, Simone Federico; Brendlinger, Kurt; Brennan, Amelia Jean; Brenner, Lydia; Brenner, Richard; Bressler, Shikma; Bristow, Kieran; Bristow, Timothy Michael; Britton, Dave; Britzger, Daniel; Brochu, Frederic; Brock, Ian; Brock, Raymond; Bronner, Johanna; Brooijmans, Gustaaf; Brooks, Timothy; Brooks, William; Brosamer, Jacquelyn; Brost, Elizabeth; Brown, Jonathan; Bruckman de Renstrom, Pawel; Bruncko, Dusan; Bruneliere, Renaud; Bruni, Alessia; Bruni, Graziano; Bruschi, Marco; Bryngemark, Lene; Buanes, Trygve; Buat, Quentin; Buchholz, Peter; Buckley, Andrew; Buda, Stelian Ioan; Budagov, Ioulian; Buehrer, Felix; Bugge, Lars; Bugge, Magnar Kopangen; Bulekov, Oleg; Burckhart, Helfried; Burdin, Sergey; Burghgrave, Blake; Burke, Stephen; Burmeister, Ingo; Busato, Emmanuel; Büscher, Daniel; Büscher, Volker; Bussey, Peter; Buszello, Claus-Peter; Butler, John; Butt, Aatif Imtiaz; Buttar, Craig; Butterworth, Jonathan; Butti, Pierfrancesco; Buttinger, William; Buzatu, Adrian; Buzykaev, Aleksey; Cabrera Urbán, Susana; Caforio, Davide; Cakir, Orhan; Calafiura, Paolo; Calandri, Alessandro; Calderini, Giovanni; Calfayan, Philippe; Caloba, Luiz; Calvet, David; Calvet, Samuel; Camacho Toro, Reina; Camarda, Stefano; Cameron, David; Caminada, Lea Michaela; Caminal Armadans, Roger; Campana, Simone; Campanelli, Mario; Campoverde, Angel; Canale, Vincenzo; Canepa, Anadi; Cano Bret, Marc; Cantero, Josu; Cantrill, Robert; Cao, Tingting; Capeans Garrido, Maria Del Mar; Caprini, Irinel; Caprini, Mihai; Capua, Marcella; Caputo, Regina; Cardarelli, Roberto; Carli, Tancredi; Carlino, Gianpaolo; Carminati, Leonardo; Caron, Sascha; Carquin, Edson; Carrillo-Montoya, German D; Carter, Janet; Carvalho, João; Casadei, Diego; Casado, Maria Pilar; Casolino, Mirkoantonio; Castaneda-Miranda, Elizabeth; Castelli, Angelantonio; Castillo Gimenez, Victoria; Castro, Nuno Filipe; Catastini, Pierluigi; Catinaccio, Andrea; Catmore, James; Cattai, Ariella; Caudron, Julien; Cavaliere, Viviana; Cavalli, Donatella; Cavalli-Sforza, Matteo; Cavasinni, Vincenzo; Ceradini, Filippo; Cerio, Benjamin; Cerny, Karel; Santiago Cerqueira, Augusto; Cerri, Alessandro; Cerrito, Lucio; Cerutti, Fabio; Cerv, Matevz; Cervelli, Alberto; Cetin, Serkant Ali; Chafaq, Aziz; Chakraborty, Dhiman; Chalupkova, Ina; Chang, Philip; Chapleau, Bertrand; Chapman, John Derek; Charlton, Dave; Chau, Chav Chhiv; Chavez Barajas, Carlos Alberto; Cheatham, Susan; Chegwidden, Andrew; Chekanov, Sergei; Chekulaev, Sergey; Chelkov, Gueorgui; Chelstowska, Magda Anna; Chen, Chunhui; Chen, Hucheng; Chen, Karen; Chen, Liming; Chen, Shenjian; Chen, Xin; Chen, Ye; Cheng, Hok Chuen; Cheng, Yangyang; Cheplakov, Alexander; Cheremushkina, Evgenia; Cherkaoui El Moursli, Rajaa; Chernyatin, Valeriy; Cheu, Elliott; Chevalier, Laurent; Chiarella, Vitaliano; Childers, John Taylor; Chiodini, Gabriele; Chisholm, Andrew; Chislett, Rebecca Thalatta; Chitan, Adrian; Chizhov, Mihail; Choi, Kyungeon; Chouridou, Sofia; Chow, Bonnie Kar Bo; Christodoulou, Valentinos; Chromek-Burckhart, Doris; Chu, Ming-Lee; Chudoba, Jiri; Chuinard, Annabelle Julia; Chwastowski, Janusz; Chytka, Ladislav; Ciapetti, Guido; Ciftci, Abbas Kenan; Cinca, Diane; Cindro, Vladimir; Cioara, Irina Antonela; Ciocio, Alessandra; Citron, Zvi Hirsh; Ciubancan, Mihai; Clark, Allan G; Clark, Brian Lee; Clark, Philip James; Clarke, Robert; Cleland, Bill; Clement, Christophe; Coadou, Yann; Cobal, Marina; Coccaro, Andrea; Cochran, James H; Coffey, Laurel; Cogan, Joshua Godfrey; Cole, Brian; Cole, Stephen; Colijn, Auke-Pieter; Collot, Johann; Colombo, Tommaso; Compostella, Gabriele; Conde Muiño, Patricia; Coniavitis, Elias; Connell, Simon Henry; Connelly, Ian; Consonni, Sofia Maria; Consorti, Valerio; Constantinescu, Serban; Conta, Claudio; Conti, Geraldine; Conventi, Francesco; Cooke, Mark; Cooper, Ben; Cooper-Sarkar, Amanda; Copic, Katherine; Cornelissen, Thijs; Corradi, Massimo; Corriveau, Francois; Corso-Radu, Alina; Cortes-Gonzalez, Arely; Cortiana, Giorgio; Costa, Giuseppe; Costa, María José; Costanzo, Davide; Côté, David; Cottin, Giovanna; Cowan, Glen; Cox, Brian; Cranmer, Kyle; Cree, Graham; Crépé-Renaudin, Sabine; Crescioli, Francesco; Cribbs, Wayne Allen; Crispin Ortuzar, Mireia; Cristinziani, Markus; Croft, Vince; Crosetti, Giovanni; Cuhadar Donszelmann, Tulay; Cummings, Jane; Curatolo, Maria; Cuthbert, Cameron; Czirr, Hendrik; Czodrowski, Patrick; D'Auria, Saverio; D'Onofrio, Monica; Da Cunha Sargedas De Sousa, Mario Jose; Da Via, Cinzia; Dabrowski, Wladyslaw; Dafinca, Alexandru; Dai, Tiesheng; Dale, Orjan; Dallaire, Frederick; Dallapiccola, Carlo; Dam, Mogens; Dandoy, Jeffrey Rogers; Daniells, Andrew Christopher; Danninger, Matthias; Dano Hoffmann, Maria; Dao, Valerio; Darbo, Giovanni; Darmora, Smita; Dassoulas, James; Dattagupta, Aparajita; Davey, Will; David, Claire; Davidek, Tomas; Davies, Eleanor; Davies, Merlin; Davison, Peter; Davygora, Yuriy; Dawe, Edmund; Dawson, Ian; Daya-Ishmukhametova, Rozmin; De, Kaushik; de Asmundis, Riccardo; De Castro, Stefano; De Cecco, Sandro; De Groot, Nicolo; de Jong, Paul; De la Torre, Hector; De Lorenzi, Francesco; De Nooij, Lucie; De Pedis, Daniele; De Salvo, Alessandro; De Sanctis, Umberto; De Santo, Antonella; De Vivie De Regie, Jean-Baptiste; Dearnaley, William James; Debbe, Ramiro; Debenedetti, Chiara; Dedovich, Dmitri; Deigaard, Ingrid; Del Peso, Jose; Del Prete, Tarcisio; Delgove, David; Deliot, Frederic; Delitzsch, Chris Malena; Deliyergiyev, Maksym; Dell'Acqua, Andrea; Dell'Asta, Lidia; Dell'Orso, Mauro; Della Pietra, Massimo; della Volpe, Domenico; Delmastro, Marco; Delsart, Pierre-Antoine; Deluca, Carolina; DeMarco, David; Demers, Sarah; Demichev, Mikhail; Demilly, Aurelien; Denisov, Sergey; Derendarz, Dominik; Derkaoui, Jamal Eddine; Derue, Frederic; Dervan, Paul; Desch, Klaus Kurt; Deterre, Cecile; Deviveiros, Pier-Olivier; Dewhurst, Alastair; Dhaliwal, Saminder; Di Ciaccio, Anna; Di Ciaccio, Lucia; Di Domenico, Antonio; Di Donato, Camilla; Di Girolamo, Alessandro; Di Girolamo, Beniamino; Di Mattia, Alessandro; Di Micco, Biagio; Di Nardo, Roberto; Di Simone, Andrea; Di Sipio, Riccardo; Di Valentino, David; Diaconu, Cristinel; Diamond, Miriam; Dias, Flavia; Diaz, Marco Aurelio; Diehl, Edward; Dietrich, Janet; Diglio, Sara; Dimitrievska, Aleksandra; Dingfelder, Jochen; Dittus, Fridolin; Djama, Fares; Djobava, Tamar; Djuvsland, Julia Isabell; Barros do Vale, Maria Aline; Dobos, Daniel; Dobre, Monica; Doglioni, Caterina; Dohmae, Takeshi; Dolejsi, Jiri; Dolezal, Zdenek; Dolgoshein, Boris; Donadelli, Marisilvia; Donati, Simone; Dondero, Paolo; Donini, Julien; Dopke, Jens; Doria, Alessandra; Dova, Maria-Teresa; Doyle, Tony; Drechsler, Eric; Dris, Manolis; Dubreuil, Emmanuelle; Duchovni, Ehud; Duckeck, Guenter; Ducu, Otilia Anamaria; Duda, Dominik; Dudarev, Alexey; Duflot, Laurent; Duguid, Liam; Dührssen, Michael; Dunford, Monica; Duran Yildiz, Hatice; Düren, Michael; Durglishvili, Archil; Duschinger, Dirk; Dwuznik, Michal; Dyndal, Mateusz; Eckardt, Christoph; Ecker, Katharina Maria; Edson, William; Edwards, Nicholas Charles; Ehrenfeld, Wolfgang; Eifert, Till; Eigen, Gerald; Einsweiler, Kevin; Ekelof, Tord; El Kacimi, Mohamed; Ellert, Mattias; Elles, Sabine; Ellinghaus, Frank; Elliot, Alison; Ellis, Nicolas; Elmsheuser, Johannes; Elsing, Markus; Emeliyanov, Dmitry; Enari, Yuji; Endner, Oliver Chris; Endo, Masaki; Engelmann, Roderich; Erdmann, Johannes; Ereditato, Antonio; Ernis, Gunar; Ernst, Jesse; Ernst, Michael; Errede, Steven; Ertel, Eugen; Escalier, Marc; Esch, Hendrik; Escobar, Carlos; Esposito, Bellisario; Etienvre, Anne-Isabelle; Etzion, Erez; Evans, Hal; Ezhilov, Alexey; Fabbri, Laura; Facini, Gabriel; Fakhrutdinov, Rinat; Falciano, Speranza; Falla, Rebecca Jane; Faltova, Jana; Fang, Yaquan; Fanti, Marcello; Farbin, Amir; Farilla, Addolorata; Farooque, Trisha; Farrell, Steven; Farrington, Sinead; Farthouat, Philippe; Fassi, Farida; Fassnacht, Patrick; Fassouliotis, Dimitrios; Favareto, Andrea; Fayard, Louis; Federic, Pavol; Fedin, Oleg; Fedorko, Wojciech; Feigl, Simon; Feligioni, Lorenzo; Feng, Cunfeng; Feng, Eric; Feng, Haolu; Fenyuk, Alexander; Fernandez Martinez, Patricia; Fernandez Perez, Sonia; Ferrag, Samir; Ferrando, James; Ferrari, Arnaud; Ferrari, Pamela; Ferrari, Roberto; Ferreira de Lima, Danilo Enoque; Ferrer, Antonio; Ferrere, Didier; Ferretti, Claudio; Ferretto Parodi, Andrea; Fiascaris, Maria; Fiedler, Frank; Filipčič, Andrej; Filipuzzi, Marco; Filthaut, Frank; Fincke-Keeler, Margret; Finelli, Kevin Daniel; Fiolhais, Miguel; Fiorini, Luca; Firan, Ana; Fischer, Adam; Fischer, Cora; Fischer, Julia; Fisher, Wade Cameron; Fitzgerald, Eric Andrew; Flechl, Martin; Fleck, Ivor; Fleischmann, Philipp; Fleischmann, Sebastian; Fletcher, Gareth Thomas; Fletcher, Gregory; Flick, Tobias; Floderus, Anders; Flores Castillo, Luis; Flowerdew, Michael; Formica, Andrea; Forti, Alessandra; Fournier, Daniel; Fox, Harald; Fracchia, Silvia; Francavilla, Paolo; Franchini, Matteo; Francis, David; Franconi, Laura; Franklin, Melissa; Fraternali, Marco; Freeborn, David; French, Sky; Friedrich, Felix; Froidevaux, Daniel; Frost, James; Fukunaga, Chikara; Fullana Torregrosa, Esteban; Fulsom, Bryan Gregory; Fuster, Juan; Gabaldon, Carolina; Gabizon, Ofir; Gabrielli, Alessandro; Gabrielli, Andrea; Gadatsch, Stefan; Gadomski, Szymon; Gagliardi, Guido; Gagnon, Pauline; Galea, Cristina; Galhardo, Bruno; Gallas, Elizabeth; Gallop, Bruce; Gallus, Petr; Galster, Gorm Aske Gram Krohn; Gan, KK; Gao, Jun; Gao, Yanyan; Gao, Yongsheng; Garay Walls, Francisca; Garberson, Ford; García, Carmen; García Navarro, José Enrique; Garcia-Sciveres, Maurice; Gardner, Robert; Garelli, Nicoletta; Garonne, Vincent; Gatti, Claudio; Gaudiello, Andrea; Gaudio, Gabriella; Gaur, Bakul; Gauthier, Lea; Gauzzi, Paolo; Gavrilenko, Igor; Gay, Colin; Gaycken, Goetz; Gazis, Evangelos; Ge, Peng; Gecse, Zoltan; Gee, Norman; Geerts, Daniël Alphonsus Adrianus; Geich-Gimbel, Christoph; Geisler, Manuel Patrice; Gemme, Claudia; Genest, Marie-Hélène; Gentile, Simonetta; George, Matthias; George, Simon; Gerbaudo, Davide; Gershon, Avi; Ghazlane, Hamid; Ghodbane, Nabil; Giacobbe, Benedetto; Giagu, Stefano; Giangiobbe, Vincent; Giannetti, Paola; Gibbard, Bruce; Gibson, Stephen; Gilchriese, Murdock; Gillam, Thomas; Gillberg, Dag; Gilles, Geoffrey; Gingrich, Douglas; Giokaris, Nikos; Giordani, MarioPaolo; Giorgi, Filippo Maria; Giorgi, Francesco Michelangelo; Giraud, Pierre-Francois; Giromini, Paolo; Giugni, Danilo; Giuliani, Claudia; Giulini, Maddalena; Gjelsten, Børge Kile; Gkaitatzis, Stamatios; Gkialas, Ioannis; Gkougkousis, Evangelos Leonidas; Gladilin, Leonid; Glasman, Claudia; Glatzer, Julian; Glaysher, Paul; Glazov, Alexandre; Goblirsch-Kolb, Maximilian; Goddard, Jack Robert; Godlewski, Jan; Goldfarb, Steven; Golling, Tobias; Golubkov, Dmitry; Gomes, Agostinho; Gonçalo, Ricardo; Goncalves Pinto Firmino Da Costa, Joao; Gonella, Laura; González de la Hoz, Santiago; Gonzalez Parra, Garoe; Gonzalez-Sevilla, Sergio; Goossens, Luc; Gorbounov, Petr Andreevich; Gordon, Howard; Gorelov, Igor; Gorini, Benedetto; Gorini, Edoardo; Gorišek, Andrej; Gornicki, Edward; Goshaw, Alfred; Gössling, Claus; Gostkin, Mikhail Ivanovitch; Goujdami, Driss; Goussiou, Anna; Govender, Nicolin; Grabas, Herve Marie Xavier; Graber, Lars; Grabowska-Bold, Iwona; Grafström, Per; Grahn, Karl-Johan; Gramling, Johanna; Gramstad, Eirik; Grancagnolo, Sergio; Grassi, Valerio; Gratchev, Vadim; Gray, Heather; Graziani, Enrico; Greenwood, Zeno Dixon; Gregersen, Kristian; Gregor, Ingrid-Maria; Grenier, Philippe; Griffiths, Justin; Grillo, Alexander; Grimm, Kathryn; Grinstein, Sebastian; Gris, Philippe Luc Yves; Grishkevich, Yaroslav; Grivaz, Jean-Francois; Grohs, Johannes Philipp; Grohsjean, Alexander; Gross, Eilam; Grosse-Knetter, Joern; Grossi, Giulio Cornelio; Grout, Zara Jane; Guan, Liang; Guenther, Jaroslav; Guescini, Francesco; Guest, Daniel; Gueta, Orel; Guido, Elisa; Guillemin, Thibault; Guindon, Stefan; Gul, Umar; Gumpert, Christian; Guo, Jun; Gupta, Shaun; Gutierrez, Phillip; Gutierrez Ortiz, Nicolas Gilberto; Gutschow, Christian; Guyot, Claude; Gwenlan, Claire; Gwilliam, Carl; Haas, Andy; Haber, Carl; Hadavand, Haleh Khani; Haddad, Nacim; Haefner, Petra; Hageböck, Stephan; Hajduk, Zbigniew; Hakobyan, Hrachya; Haleem, Mahsana; Haley, Joseph; Hall, David; Halladjian, Garabed; Hallewell, Gregory David; Hamacher, Klaus; Hamal, Petr; Hamano, Kenji; Hamer, Matthias; Hamilton, Andrew; Hamilton, Samuel; Hamity, Guillermo Nicolas; Hamnett, Phillip George; Han, Liang; Hanagaki, Kazunori; Hanawa, Keita; Hance, Michael; Hanke, Paul; Hanna, Remie; Hansen, Jørgen Beck; Hansen, Jorn Dines; Hansen, Maike Christina; Hansen, Peter Henrik; Hara, Kazuhiko; Hard, Andrew; Harenberg, Torsten; Hariri, Faten; Harkusha, Siarhei; Harrington, Robert; Harrison, Paul Fraser; Hartjes, Fred; Hasegawa, Makoto; Hasegawa, Satoshi; Hasegawa, Yoji; Hasib, A; Hassani, Samira; Haug, Sigve; Hauser, Reiner; Hauswald, Lorenz; Havranek, Miroslav; Hawkes, Christopher; Hawkings, Richard John; Hawkins, Anthony David; Hayashi, Takayasu; Hayden, Daniel; Hays, Chris; Hays, Jonathan Michael; Hayward, Helen; Haywood, Stephen; Head, Simon; Heck, Tobias; Hedberg, Vincent; Heelan, Louise; Heim, Sarah; Heim, Timon; Heinemann, Beate; Heinrich, Lukas; Hejbal, Jiri; Helary, Louis; Hellman, Sten; Hellmich, Dennis; Helsens, Clement; Henderson, James; Henderson, Robert; Heng, Yang; Hengler, Christopher; Henrichs, Anna; Henriques Correia, Ana Maria; Henrot-Versille, Sophie; Herbert, Geoffrey Henry; Hernández Jiménez, Yesenia; Herrberg-Schubert, Ruth; Herten, Gregor; Hertenberger, Ralf; Hervas, Luis; Hesketh, Gavin Grant; Hessey, Nigel; Hetherly, Jeffrey Wayne; Hickling, Robert; Higón-Rodriguez, Emilio; Hill, Ewan; Hill, John; Hiller, Karl Heinz; Hillier, Stephen; Hinchliffe, Ian; Hines, Elizabeth; Hinman, Rachel Reisner; Hirose, Minoru; Hirschbuehl, Dominic; Hobbs, John; Hod, Noam; Hodgkinson, Mark; Hodgson, Paul; Hoecker, Andreas; Hoeferkamp, Martin; Hoenig, Friedrich; Hohlfeld, Marc; Hohn, David; Holmes, Tova Ray; Hong, Tae Min; Hooft van Huysduynen, Loek; Hopkins, Walter; Horii, Yasuyuki; Horton, Arthur James; Hostachy, Jean-Yves; Hou, Suen; Hoummada, Abdeslam; Howard, Jacob; Howarth, James; Hrabovsky, Miroslav; Hristova, Ivana; Hrivnac, Julius; Hryn'ova, Tetiana; Hrynevich, Aliaksei; Hsu, Catherine; Hsu, Pai-hsien Jennifer; Hsu, Shih-Chieh; Hu, Diedi; Hu, Qipeng; Hu, Xueye; Huang, Yanping; Hubacek, Zdenek; Hubaut, Fabrice; Huegging, Fabian; Huffman, Todd Brian; Hughes, Emlyn; Hughes, Gareth; Huhtinen, Mika; Hülsing, Tobias Alexander; Huseynov, Nazim; Huston, Joey; Huth, John; Iacobucci, Giuseppe; Iakovidis, Georgios; Ibragimov, Iskander; Iconomidou-Fayard, Lydia; Ideal, Emma; Idrissi, Zineb; Iengo, Paolo; Igonkina, Olga; Iizawa, Tomoya; Ikegami, Yoichi; Ikematsu, Katsumasa; Ikeno, Masahiro; Ilchenko, Iurii; Iliadis, Dimitrios; Ilic, Nikolina; Inamaru, Yuki; Ince, Tayfun; Ioannou, Pavlos; Iodice, Mauro; Iordanidou, Kalliopi; Ippolito, Valerio; Irles Quiles, Adrian; Isaksson, Charlie; Ishino, Masaya; Ishitsuka, Masaki; Ishmukhametov, Renat; Issever, Cigdem; Istin, Serhat; Iturbe Ponce, Julia Mariana; Iuppa, Roberto; Ivarsson, Jenny; Iwanski, Wieslaw; Iwasaki, Hiroyuki; Izen, Joseph; Izzo, Vincenzo; Jabbar, Samina; Jackson, Brett; Jackson, Matthew; Jackson, Paul; Jaekel, Martin; Jain, Vivek; Jakobs, Karl; Jakobsen, Sune; Jakoubek, Tomas; Jakubek, Jan; Jamin, David Olivier; Jana, Dilip; Jansen, Eric; Jansky, Roland; Janssen, Jens; Janus, Michel; Jarlskog, Göran; Javadov, Namig; Javůrek, Tomáš; Jeanty, Laura; Jejelava, Juansher; Jeng, Geng-yuan; Jennens, David; Jenni, Peter; Jentzsch, Jennifer; Jeske, Carl; Jézéquel, Stéphane; Ji, Haoshuang; Jia, Jiangyong; Jiang, Yi; Jimenez Pena, Javier; Jin, Shan; Jinaru, Adam; Jinnouchi, Osamu; Joergensen, Morten Dam; Johansson, Per; Johns, Kenneth; Jon-And, Kerstin; Jones, Graham; Jones, Roger; Jones, Tim; Jongmanns, Jan; Jorge, Pedro; Joshi, Kiran Daniel; Jovicevic, Jelena; Ju, Xiangyang; Jung, Christian; Jussel, Patrick; Juste Rozas, Aurelio; Kaci, Mohammed; Kaczmarska, Anna; Kado, Marumi; Kagan, Harris; Kagan, Michael; Kahn, Sebastien Jonathan; Kajomovitz, Enrique; Kalderon, Charles William; Kama, Sami; Kamenshchikov, Andrey; Kanaya, Naoko; Kaneda, Michiru; Kaneti, Steven; Kantserov, Vadim; Kanzaki, Junichi; Kaplan, Benjamin; Kapliy, Anton; Kar, Deepak; Karakostas, Konstantinos; Karamaoun, Andrew; Karastathis, Nikolaos; Kareem, Mohammad Jawad; Karnevskiy, Mikhail; Karpov, Sergey; Karpova, Zoya; Karthik, Krishnaiyengar; Kartvelishvili, Vakhtang; Karyukhin, Andrey; Kashif, Lashkar; Kass, Richard; Kastanas, Alex; Kataoka, Yousuke; Katre, Akshay; Katzy, Judith; Kawagoe, Kiyotomo; Kawamoto, Tatsuo; Kawamura, Gen; Kazama, Shingo; Kazanin, Vassili; Kazarinov, Makhail; Keeler, Richard; Kehoe, Robert; Keil, Markus; Keller, John; Kempster, Jacob Julian; Keoshkerian, Houry; Kepka, Oldrich; Kerševan, Borut Paul; Kersten, Susanne; Keyes, Robert; Khalil-zada, Farkhad; Khandanyan, Hovhannes; Khanov, Alexander; Kharlamov, Alexey; Khoo, Teng Jian; Khoriauli, Gia; Khovanskiy, Valery; Khramov, Evgeniy; Khubua, Jemal; Kim, Hee Yeun; Kim, Hyeon Jin; Kim, Shinhong; Kim, Young-Kee; Kimura, Naoki; Kind, Oliver Maria; King, Barry; King, Matthew; King, Robert Steven Beaufoy; King, Samuel Burton; Kirk, Julie; Kiryunin, Andrey; Kishimoto, Tomoe; Kisielewska, Danuta; Kiss, Florian; Kiuchi, Kenji; Kladiva, Eduard; Klein, Matthew Henry; Klein, Max; Klein, Uta; Kleinknecht, Konrad; Klimek, Pawel; Klimentov, Alexei; Klingenberg, Reiner; Klinger, Joel Alexander; Klioutchnikova, Tatiana; Klok, Peter; Kluge, Eike-Erik; Kluit, Peter; Kluth, Stefan; Kneringer, Emmerich; Knoops, Edith; Knue, Andrea; Kobayashi, Dai; Kobayashi, Tomio; Kobel, Michael; Kocian, Martin; Kodys, Peter; Koffas, Thomas; Koffeman, Els; Kogan, Lucy Anne; Kohlmann, Simon; Kohout, Zdenek; Kohriki, Takashi; Koi, Tatsumi; Kolanoski, Hermann; Koletsou, Iro; Komar, Aston; Komori, Yuto; Kondo, Takahiko; Kondrashova, Nataliia; Köneke, Karsten; König, Adriaan; König, Sebastian; Kono, Takanori; Konoplich, Rostislav; Konstantinidis, Nikolaos; Kopeliansky, Revital; Koperny, Stefan; Köpke, Lutz; Kopp, Anna Katharina; Korcyl, Krzysztof; Kordas, Kostantinos; Korn, Andreas; Korol, Aleksandr; Korolkov, Ilya; Korolkova, Elena; Kortner, Oliver; Kortner, Sandra; Kosek, Tomas; Kostyukhin, Vadim; Kotov, Vladislav; Kotwal, Ashutosh; Kourkoumeli-Charalampidi, Athina; Kourkoumelis, Christine; Kouskoura, Vasiliki; Koutsman, Alex; Kowalewski, Robert Victor; Kowalski, Tadeusz; Kozanecki, Witold; Kozhin, Anatoly; Kramarenko, Viktor; Kramberger, Gregor; Krasnopevtsev, Dimitriy; Krasny, Mieczyslaw Witold; Krasznahorkay, Attila; Kraus, Jana; Kravchenko, Anton; Kreiss, Sven; Kretz, Moritz; Kretzschmar, Jan; Kreutzfeldt, Kristof; Krieger, Peter; Krizka, Karol; Kroeninger, Kevin; Kroha, Hubert; Kroll, Joe; Kroseberg, Juergen; Krstic, Jelena; Kruchonak, Uladzimir; Krüger, Hans; Krumnack, Nils; Krumshteyn, Zinovii; Kruse, Amanda; Kruse, Mark; Kruskal, Michael; Kubota, Takashi; Kucuk, Hilal; Kuday, Sinan; Kuehn, Susanne; Kugel, Andreas; Kuger, Fabian; Kuhl, Andrew; Kuhl, Thorsten; Kukhtin, Victor; Kulchitsky, Yuri; Kuleshov, Sergey; Kuna, Marine; Kunigo, Takuto; Kupco, Alexander; Kurashige, Hisaya; Kurochkin, Yurii; Kurumida, Rie; Kus, Vlastimil; Kuwertz, Emma Sian; Kuze, Masahiro; Kvita, Jiri; Kwan, Tony; Kyriazopoulos, Dimitrios; La Rosa, Alessandro; La Rosa Navarro, Jose Luis; La Rotonda, Laura; Lacasta, Carlos; Lacava, Francesco; Lacey, James; Lacker, Heiko; Lacour, Didier; Lacuesta, Vicente Ramón; Ladygin, Evgueni; Lafaye, Remi; Laforge, Bertrand; Lagouri, Theodota; Lai, Stanley; Lambourne, Luke; Lammers, Sabine; Lampen, Caleb; Lampl, Walter; Lançon, Eric; Landgraf, Ulrich; Landon, Murrough; Lang, Valerie Susanne; Lange, J örn Christian; Lankford, Andrew; Lanni, Francesco; Lantzsch, Kerstin; Laplace, Sandrine; Lapoire, Cecile; Laporte, Jean-Francois; Lari, Tommaso; Lasagni Manghi, Federico; Lassnig, Mario; Laurelli, Paolo; Lavrijsen, Wim; Law, Alexander; Laycock, Paul; Le Dortz, Olivier; Le Guirriec, Emmanuel; Le Menedeu, Eve; LeCompte, Thomas; Ledroit-Guillon, Fabienne Agnes Marie; Lee, Claire Alexandra; Lee, Shih-Chang; Lee, Lawrence; Lefebvre, Guillaume; Lefebvre, Michel; Legger, Federica; Leggett, Charles; Lehan, Allan; Lehmann Miotto, Giovanna; Lei, Xiaowen; Leight, William Axel; Leisos, Antonios; Leister, Andrew Gerard; Leite, Marco Aurelio Lisboa; Leitner, Rupert; Lellouch, Daniel; Lemmer, Boris; Leney, Katharine; Lenz, Tatjana; Lenzen, Georg; Lenzi, Bruno; Leone, Robert; Leone, Sandra; Leonidopoulos, Christos; Leontsinis, Stefanos; Leroy, Claude; Lester, Christopher; Levchenko, Mikhail; Levêque, Jessica; Levin, Daniel; Levinson, Lorne; Levy, Mark; Lewis, Adrian; Leyko, Agnieszka; Leyton, Michael; Li, Bing; Li, Haifeng; Li, Ho Ling; Li, Lei; Li, Liang; Li, Shu; Li, Yichen; Liang, Zhijun; Liao, Hongbo; Liberti, Barbara; Liblong, Aaron; Lichard, Peter; Lie, Ki; Liebal, Jessica; Liebig, Wolfgang; Limbach, Christian; Limosani, Antonio; Lin, Simon; Lin, Tai-Hua; Linde, Frank; Lindquist, Brian Edward; Linnemann, James; Lipeles, Elliot; Lipniacka, Anna; Lisovyi, Mykhailo; Liss, Tony; Lissauer, David; Lister, Alison; Litke, Alan; Liu, Bo; Liu, Dong; Liu, Jian; Liu, Jianbei; Liu, Kun; Liu, Lulu; Liu, Miaoyuan; Liu, Minghui; Liu, Yanwen; Livan, Michele; Lleres, Annick; Llorente Merino, Javier; Lloyd, Stephen; Lo Sterzo, Francesco; Lobodzinska, Ewelina; Loch, Peter; Lockman, William; Loebinger, Fred; Loevschall-Jensen, Ask Emil; Loginov, Andrey; Lohse, Thomas; Lohwasser, Kristin; Lokajicek, Milos; Long, Brian Alexander; Long, Jonathan; Long, Robin Eamonn; Looper, Kristina Anne; Lopes, Lourenco; Lopez Mateos, David; Lopez Paredes, Brais; Lopez Paz, Ivan; Lorenz, Jeanette; Lorenzo Martinez, Narei; Losada, Marta; Loscutoff, Peter; Lösel, Philipp Jonathan; Lou, XinChou; Lounis, Abdenour; Love, Jeremy; Love, Peter; Lu, Nan; Lubatti, Henry; Luci, Claudio; Lucotte, Arnaud; Luehring, Frederick; Lukas, Wolfgang; Luminari, Lamberto; Lundberg, Olof; Lund-Jensen, Bengt; Lungwitz, Matthias; Lynn, David; Lysak, Roman; Lytken, Else; Ma, Hong; Ma, Lian Liang; Maccarrone, Giovanni; Macchiolo, Anna; Macdonald, Calum Michael; Machado Miguens, Joana; Macina, Daniela; Madaffari, Daniele; Madar, Romain; Maddocks, Harvey Jonathan; Mader, Wolfgang; Madsen, Alexander; Maeland, Steffen; Maeno, Tadashi; Maevskiy, Artem; Magradze, Erekle; Mahboubi, Kambiz; Mahlstedt, Joern; Maiani, Camilla; Maidantchik, Carmen; Maier, Andreas Alexander; Maier, Thomas; Maio, Amélia; Majewski, Stephanie; Makida, Yasuhiro; Makovec, Nikola; Malaescu, Bogdan; Malecki, Pawel; Maleev, Victor; Malek, Fairouz; Mallik, Usha; Malon, David; Malone, Caitlin; Maltezos, Stavros; Malyshev, Vladimir; Malyukov, Sergei; Mamuzic, Judita; Mancini, Giada; Mandelli, Beatrice; Mandelli, Luciano; Mandić, Igor; Mandrysch, Rocco; Maneira, José; Manfredini, Alessandro; Manhaes de Andrade Filho, Luciano; Manjarres Ramos, Joany; Mann, Alexander; Manning, Peter; Manousakis-Katsikakis, Arkadios; Mansoulie, Bruno; Mantifel, Rodger; Mantoani, Matteo; Mapelli, Livio; March, Luis; Marchiori, Giovanni; Marcisovsky, Michal; Marino, Christopher; Marjanovic, Marija; Marroquim, Fernando; Marsden, Stephen Philip; Marshall, Zach; Marti, Lukas Fritz; Marti-Garcia, Salvador; Martin, Brian Thomas; Martin, Tim; Martin, Victoria Jane; Martin dit Latour, Bertrand; Martinez, Mario; Martin-Haugh, Stewart; Martoiu, Victor Sorin; Martyniuk, Alex; Marx, Marilyn; Marzano, Francesco; Marzin, Antoine; Masetti, Lucia; Mashimo, Tetsuro; Mashinistov, Ruslan; Masik, Jiri; Maslennikov, Alexey; Massa, Ignazio; Massa, Lorenzo; Massol, Nicolas; Mastrandrea, Paolo; Mastroberardino, Anna; Masubuchi, Tatsuya; Mättig, Peter; Mattmann, Johannes; Maurer, Julien; Maxfield, Stephen; Maximov, Dmitriy; Mazini, Rachid; Mazza, Simone Michele; Mazzaferro, Luca; Mc Goldrick, Garrin; Mc Kee, Shawn Patrick; McCarn, Allison; McCarthy, Robert; McCarthy, Tom; McCubbin, Norman; McFarlane, Kenneth; Mcfayden, Josh; Mchedlidze, Gvantsa; McMahon, Steve; McPherson, Robert; Medinnis, Michael; Meehan, Samuel; Mehlhase, Sascha; Mehta, Andrew; Meier, Karlheinz; Meineck, Christian; Meirose, Bernhard; Mellado Garcia, Bruce Rafael; Meloni, Federico; Mengarelli, Alberto; Menke, Sven; Meoni, Evelin; Mercurio, Kevin Michael; Mergelmeyer, Sebastian; Mermod, Philippe; Merola, Leonardo; Meroni, Chiara; Merritt, Frank; Messina, Andrea; Metcalfe, Jessica; Mete, Alaettin Serhan; Meyer, Carsten; Meyer, Christopher; Meyer, Jean-Pierre; Meyer, Jochen; Middleton, Robin; Miglioranzi, Silvia; Mijović, Liza; Mikenberg, Giora; Mikestikova, Marcela; Mikuž, Marko; Milesi, Marco; Milic, Adriana; Miller, David; Mills, Corrinne; Milov, Alexander; Milstead, David; Minaenko, Andrey; Minami, Yuto; Minashvili, Irakli; Mincer, Allen; Mindur, Bartosz; Mineev, Mikhail; Ming, Yao; Mir, Lluisa-Maria; Mitani, Takashi; Mitrevski, Jovan; Mitsou, Vasiliki A; Miucci, Antonio; Miyagawa, Paul; Mjörnmark, Jan-Ulf; Moa, Torbjoern; Mochizuki, Kazuya; Mohapatra, Soumya; Mohr, Wolfgang; Molander, Simon; Moles-Valls, Regina; Mönig, Klaus; Monini, Caterina; Monk, James; Monnier, Emmanuel; Montejo Berlingen, Javier; Monticelli, Fernando; Monzani, Simone; Moore, Roger; Morange, Nicolas; Moreno, Deywis; Moreno Llácer, María; Morettini, Paolo; Morgenstern, Marcus; Morii, Masahiro; Morisbak, Vanja; Moritz, Sebastian; Morley, Anthony Keith; Mornacchi, Giuseppe; Morris, John; Mortensen, Simon Stark; Morton, Alexander; Morvaj, Ljiljana; Moser, Hans-Guenther; Mosidze, Maia; Moss, Josh; Motohashi, Kazuki; Mount, Richard; Mountricha, Eleni; Mouraviev, Sergei; Moyse, Edward; Muanza, Steve; Mudd, Richard; Mueller, Felix; Mueller, James; Mueller, Klemens; Mueller, Ralph Soeren Peter; Mueller, Thibaut; Muenstermann, Daniel; Mullen, Paul; Munwes, Yonathan; Murillo Quijada, Javier Alberto; Murray, Bill; Musheghyan, Haykuhi; Musto, Elisa; Myagkov, Alexey; Myska, Miroslav; Nackenhorst, Olaf; Nadal, Jordi; Nagai, Koichi; Nagai, Ryo; Nagai, Yoshikazu; Nagano, Kunihiro; Nagarkar, Advait; Nagasaka, Yasushi; Nagata, Kazuki; Nagel, Martin; Nagy, Elemer; Nairz, Armin Michael; Nakahama, Yu; Nakamura, Koji; Nakamura, Tomoaki; Nakano, Itsuo; Namasivayam, Harisankar; Nanava, Gizo; Naranjo Garcia, Roger Felipe; Narayan, Rohin; Naumann, Thomas; Navarro, Gabriela; Nayyar, Ruchika; Neal, Homer; Nechaeva, Polina; Neep, Thomas James; Nef, Pascal Daniel; Negri, Andrea; Negrini, Matteo; Nektarijevic, Snezana; Nellist, Clara; Nelson, Andrew; Nemecek, Stanislav; Nemethy, Peter; Nepomuceno, Andre Asevedo; Nessi, Marzio; Neubauer, Mark; Neumann, Manuel; Neves, Ricardo; Nevski, Pavel; Newman, Paul; Nguyen, Duong Hai; Nickerson, Richard; Nicolaidou, Rosy; Nicquevert, Bertrand; Nielsen, Jason; Nikiforou, Nikiforos; Nikiforov, Andriy; Nikolaenko, Vladimir; Nikolic-Audit, Irena; Nikolopoulos, Konstantinos; Nilsen, Jon Kerr; Nilsson, Paul; Ninomiya, Yoichi; Nisati, Aleandro; Nisius, Richard; Nobe, Takuya; Nomachi, Masaharu; Nomidis, Ioannis; Nooney, Tamsin; Norberg, Scarlet; Nordberg, Markus; Novgorodova, Olga; Nowak, Sebastian; Nozaki, Mitsuaki; Nozka, Libor; Ntekas, Konstantinos; Nunes Hanninger, Guilherme; Nunnemann, Thomas; Nurse, Emily; Nuti, Francesco; O'Brien, Brendan Joseph; O'grady, Fionnbarr; O'Neil, Dugan; O'Shea, Val; Oakham, Gerald; Oberlack, Horst; Obermann, Theresa; Ocariz, Jose; Ochi, Atsuhiko; Ochoa, Ines; Oda, Susumu; Odaka, Shigeru; Ogren, Harold; Oh, Alexander; Oh, Seog; Ohm, Christian; Ohman, Henrik; Oide, Hideyuki; Okamura, Wataru; Okawa, Hideki; Okumura, Yasuyuki; Okuyama, Toyonobu; Olariu, Albert; Olivares Pino, Sebastian Andres; Oliveira Damazio, Denis; Oliver Garcia, Elena; Olszewski, Andrzej; Olszowska, Jolanta; Onofre, António; Onyisi, Peter; Oram, Christopher; Oreglia, Mark; Oren, Yona; Orestano, Domizia; Orlando, Nicola; Oropeza Barrera, Cristina; Orr, Robert; Osculati, Bianca; Ospanov, Rustem; Otero y Garzon, Gustavo; Otono, Hidetoshi; Ouchrif, Mohamed; Ouellette, Eric; Ould-Saada, Farid; Ouraou, Ahmimed; Oussoren, Koen Pieter; Ouyang, Qun; Ovcharova, Ana; Owen, Mark; Owen, Rhys Edward; Ozcan, Veysi Erkcan; Ozturk, Nurcan; Pachal, Katherine; Pacheco Pages, Andres; Padilla Aranda, Cristobal; Pagáčová, Martina; Pagan Griso, Simone; Paganis, Efstathios; Pahl, Christoph; Paige, Frank; Pais, Preema; Pajchel, Katarina; Palacino, Gabriel; Palestini, Sandro; Palka, Marek; Pallin, Dominique; Palma, Alberto; Pan, Yibin; Panagiotopoulou, Evgenia; Pandini, Carlo Enrico; Panduro Vazquez, William; Pani, Priscilla; Panitkin, Sergey; Paolozzi, Lorenzo; Papadopoulou, Theodora; Papageorgiou, Konstantinos; Paramonov, Alexander; Paredes Hernandez, Daniela; Parker, Michael Andrew; Parker, Kerry Ann; Parodi, Fabrizio; Parsons, John; Parzefall, Ulrich; Pasqualucci, Enrico; Passaggio, Stefano; Pastore, Fernanda; Pastore, Francesca; Pásztor, Gabriella; Pataraia, Sophio; Patel, Nikhul; Pater, Joleen; Pauly, Thilo; Pearce, James; Pearson, Benjamin; Pedersen, Lars Egholm; Pedersen, Maiken; Pedraza Lopez, Sebastian; Pedro, Rute; Peleganchuk, Sergey; Pelikan, Daniel; Peng, Haiping; Penning, Bjoern; Penwell, John; Perepelitsa, Dennis; Perez Codina, Estel; Pérez García-Estañ, María Teresa; Perini, Laura; Pernegger, Heinz; Perrella, Sabrina; Peschke, Richard; Peshekhonov, Vladimir; Peters, Krisztian; Peters, Yvonne; Petersen, Brian; Petersen, Troels; Petit, Elisabeth; Petridis, Andreas; Petridou, Chariclia; Petrolo, Emilio; Petrucci, Fabrizio; Pettersson, Nora Emilia; Pezoa, Raquel; Phillips, Peter William; Piacquadio, Giacinto; Pianori, Elisabetta; Picazio, Attilio; Piccaro, Elisa; Piccinini, Maurizio; Pickering, Mark Andrew; Piegaia, Ricardo; Pignotti, David; Pilcher, James; Pilkington, Andrew; Pina, João Antonio; Pinamonti, Michele; Pinfold, James; Pingel, Almut; Pinto, Belmiro; Pires, Sylvestre; Pitt, Michael; Pizio, Caterina; Plazak, Lukas; Pleier, Marc-Andre; Pleskot, Vojtech; Plotnikova, Elena; Plucinski, Pawel; Pluth, Daniel; Poettgen, Ruth; Poggioli, Luc; Pohl, David-leon; Polesello, Giacomo; Policicchio, Antonio; Polifka, Richard; Polini, Alessandro; Pollard, Christopher Samuel; Polychronakos, Venetios; Pommès, Kathy; Pontecorvo, Ludovico; Pope, Bernard; Popeneciu, Gabriel Alexandru; Popovic, Dragan; Poppleton, Alan; Pospisil, Stanislav; Potamianos, Karolos; Potrap, Igor; Potter, Christina; Potter, Christopher; Poulard, Gilbert; Poveda, Joaquin; Pozdnyakov, Valery; Pralavorio, Pascal; Pranko, Aliaksandr; Prasad, Srivas; Prell, Soeren; Price, Darren; Price, Joe; Price, Lawrence; Primavera, Margherita; Prince, Sebastien; Proissl, Manuel; Prokofiev, Kirill; Prokoshin, Fedor; Protopapadaki, Eftychia-sofia; Protopopescu, Serban; Proudfoot, James; Przybycien, Mariusz; Ptacek, Elizabeth; Puddu, Daniele; Pueschel, Elisa; Puldon, David; Purohit, Milind; Puzo, Patrick; Qian, Jianming; Qin, Gang; Qin, Yang; Quadt, Arnulf; Quarrie, David; Quayle, William; Queitsch-Maitland, Michaela; Quilty, Donnchadha; Radeka, Veljko; Radescu, Voica; Radhakrishnan, Sooraj Krishnan; Radloff, Peter; Rados, Pere; Ragusa, Francesco; Rahal, Ghita; Rajagopalan, Srinivasan; Rammensee, Michael; Rangel-Smith, Camila; Rauscher, Felix; Rave, Stefan; Ravenscroft, Thomas; Raymond, Michel; Read, Alexander Lincoln; Readioff, Nathan Peter; Rebuzzi, Daniela; Redelbach, Andreas; Redlinger, George; Reece, Ryan; Reeves, Kendall; Rehnisch, Laura; Reisin, Hernan; Relich, Matthew; Rembser, Christoph; Ren, Huan; Renaud, Adrien; Rescigno, Marco; Resconi, Silvia; Rezanova, Olga; Reznicek, Pavel; Rezvani, Reyhaneh; Richter, Robert; Richter, Stefan; Richter-Was, Elzbieta; Ricken, Oliver; Ridel, Melissa; Rieck, Patrick; Riegel, Christian Johann; Rieger, Julia; Rijssenbeek, Michael; Rimoldi, Adele; Rinaldi, Lorenzo; Ristić, Branislav; Ritsch, Elmar; Riu, Imma; Rizatdinova, Flera; Rizvi, Eram; Robertson, Steven; Robichaud-Veronneau, Andree; Robinson, Dave; Robinson, James; Robson, Aidan; Roda, Chiara; Roe, Shaun; Røhne, Ole; Rolli, Simona; Romaniouk, Anatoli; Romano, Marino; Romano Saez, Silvestre Marino; Romero Adam, Elena; Rompotis, Nikolaos; Ronzani, Manfredi; Roos, Lydia; Ros, Eduardo; Rosati, Stefano; Rosbach, Kilian; Rose, Peyton; Rosendahl, Peter Lundgaard; Rosenthal, Oliver; Rossetti, Valerio; Rossi, Elvira; Rossi, Leonardo Paolo; Rosten, Rachel; Rotaru, Marina; Roth, Itamar; Rothberg, Joseph; Rousseau, David; Royon, Christophe; Rozanov, Alexandre; Rozen, Yoram; Ruan, Xifeng; Rubbo, Francesco; Rubinskiy, Igor; Rud, Viacheslav; Rudolph, Christian; Rudolph, Matthew Scott; Rühr, Frederik; Ruiz-Martinez, Aranzazu; Rurikova, Zuzana; Rusakovich, Nikolai; Ruschke, Alexander; Russell, Heather; Rutherfoord, John; Ruthmann, Nils; Ryabov, Yury; Rybar, Martin; Rybkin, Grigori; Ryder, Nick; Saavedra, Aldo; Sabato, Gabriele; Sacerdoti, Sabrina; Saddique, Asif; Sadrozinski, Hartmut; Sadykov, Renat; Safai Tehrani, Francesco; Saimpert, Matthias; Sakamoto, Hiroshi; Sakurai, Yuki; Salamanna, Giuseppe; Salamon, Andrea; Saleem, Muhammad; Salek, David; Sales De Bruin, Pedro Henrique; Salihagic, Denis; Salnikov, Andrei; Salt, José; Salvatore, Daniela; Salvatore, Pasquale Fabrizio; Salvucci, Antonio; Salzburger, Andreas; Sampsonidis, Dimitrios; Sanchez, Arturo; Sánchez, Javier; Sanchez Martinez, Victoria; Sandaker, Heidi; Sandbach, Ruth Laura; Sander, Heinz Georg; Sanders, Michiel; Sandhoff, Marisa; Sandoval, Carlos; Sandstroem, Rikard; Sankey, Dave; Sansoni, Andrea; Santoni, Claudio; Santonico, Rinaldo; Santos, Helena; Santoyo Castillo, Itzebelt; Sapp, Kevin; Sapronov, Andrey; Saraiva, João; Sarrazin, Bjorn; Sasaki, Osamu; Sasaki, Yuichi; Sato, Koji; Sauvage, Gilles; Sauvan, Emmanuel; Savage, Graham; Savard, Pierre; Sawyer, Craig; Sawyer, Lee; Saxon, James; Sbarra, Carla; Sbrizzi, Antonio; Scanlon, Tim; Scannicchio, Diana; Scarcella, Mark; Scarfone, Valerio; Schaarschmidt, Jana; Schacht, Peter; Schaefer, Douglas; Schaefer, Ralph; Schaeffer, Jan; Schaepe, Steffen; Schaetzel, Sebastian; Schäfer, Uli; Schaffer, Arthur; Schaile, Dorothee; Schamberger, R~Dean; Scharf, Veit; Schegelsky, Valery; Scheirich, Daniel; Schernau, Michael; Schiavi, Carlo; Schillo, Christian; Schioppa, Marco; Schlenker, Stefan; Schmidt, Evelyn; Schmieden, Kristof; Schmitt, Christian; Schmitt, Sebastian; Schmitt, Stefan; Schneider, Basil; Schnellbach, Yan Jie; Schnoor, Ulrike; Schoeffel, Laurent; Schoening, Andre; Schoenrock, Bradley Daniel; Schopf, Elisabeth; Schorlemmer, Andre Lukas; Schott, Matthias; Schouten, Doug; Schovancova, Jaroslava; Schramm, Steven; Schreyer, Manuel; Schroeder, Christian; Schuh, Natascha; Schultens, Martin Johannes; Schultz-Coulon, Hans-Christian; Schulz, Holger; Schumacher, Markus; Schumm, Bruce; Schune, Philippe; Schwanenberger, Christian; Schwartzman, Ariel; Schwarz, Thomas Andrew; Schwegler, Philipp; Schwemling, Philippe; Schwienhorst, Reinhard; Schwindling, Jerome; Schwindt, Thomas; Schwoerer, Maud; Sciacca, Gianfranco; Scifo, Estelle; Sciolla, Gabriella; Scuri, Fabrizio; Scutti, Federico; Searcy, Jacob; Sedov, George; Sedykh, Evgeny; Seema, Pienpen; Seidel, Sally; Seiden, Abraham; Seifert, Frank; Seixas, José; Sekhniaidze, Givi; Sekula, Stephen; Selbach, Karoline Elfriede; Seliverstov, Dmitry; Semprini-Cesari, Nicola; Serfon, Cedric; Serin, Laurent; Serkin, Leonid; Serre, Thomas; Seuster, Rolf; Severini, Horst; Sfiligoj, Tina; Sforza, Federico; Sfyrla, Anna; Shabalina, Elizaveta; Shamim, Mansoora; Shan, Lianyou; Shang, Ruo-yu; Shank, James; Shapiro, Marjorie; Shatalov, Pavel; Shaw, Kate; Shcherbakova, Anna; Shehu, Ciwake Yusufu; Sherwood, Peter; Shi, Liaoshan; Shimizu, Shima; Shimmin, Chase Owen; Shimojima, Makoto; Shiyakova, Mariya; Shmeleva, Alevtina; Shoaleh Saadi, Diane; Shochet, Mel; Shojaii, Seyedruhollah; Shrestha, Suyog; Shulga, Evgeny; Shupe, Michael; Shushkevich, Stanislav; Sicho, Petr; Sidiropoulou, Ourania; Sidorov, Dmitri; Sidoti, Antonio; Siegert, Frank; Sijacki, Djordje; Silva, José; Silver, Yiftah; Silverstein, Samuel; Simak, Vladislav; Simard, Olivier; Simic, Ljiljana; Simion, Stefan; Simioni, Eduard; Simmons, Brinick; Simon, Dorian; Simoniello, Rosa; Sinervo, Pekka; Sinev, Nikolai; Siragusa, Giovanni; Sisakyan, Alexei; Sivoklokov, Serguei; Sjölin, Jörgen; Sjursen, Therese; Skinner, Malcolm Bruce; Skottowe, Hugh Philip; Skubic, Patrick; Slater, Mark; Slavicek, Tomas; Slawinska, Magdalena; Sliwa, Krzysztof; Smakhtin, Vladimir; Smart, Ben; Smestad, Lillian; Smirnov, Sergei; Smirnov, Yury; Smirnova, Lidia; Smirnova, Oxana; Smith, Matthew; Smizanska, Maria; Smolek, Karel; Snesarev, Andrei; Snidero, Giacomo; Snyder, Scott; Sobie, Randall; Socher, Felix; Soffer, Abner; Soh, Dart-yin; Solans, Carlos; Solar, Michael; Solc, Jaroslav; Soldatov, Evgeny; Soldevila, Urmila; Solodkov, Alexander; Soloshenko, Alexei; Solovyanov, Oleg; Solovyev, Victor; Sommer, Philip; Song, Hong Ye; Soni, Nitesh; Sood, Alexander; Sopczak, Andre; Sopko, Bruno; Sopko, Vit; Sorin, Veronica; Sosa, David; Sosebee, Mark; Sotiropoulou, Calliope Louisa; Soualah, Rachik; Soueid, Paul; Soukharev, Andrey; South, David; Spagnolo, Stefania; Spalla, Margherita; Spanò, Francesco; Spearman, William Robert; Spettel, Fabian; Spighi, Roberto; Spigo, Giancarlo; Spiller, Laurence Anthony; Spousta, Martin; Spreitzer, Teresa; St Denis, Richard Dante; Staerz, Steffen; Stahlman, Jonathan; Stamen, Rainer; Stamm, Soren; Stanecka, Ewa; Stanescu, Cristian; Stanescu-Bellu, Madalina; Stanitzki, Marcel Michael; Stapnes, Steinar; Starchenko, Evgeny; Stark, Jan; Staroba, Pavel; Starovoitov, Pavel; Staszewski, Rafal; Stavina, Pavel; Steinberg, Peter; Stelzer, Bernd; Stelzer, Harald Joerg; Stelzer-Chilton, Oliver; Stenzel, Hasko; Stern, Sebastian; Stewart, Graeme; Stillings, Jan Andre; Stockton, Mark; Stoebe, Michael; Stoicea, Gabriel; Stolte, Philipp; Stonjek, Stefan; Stradling, Alden; Straessner, Arno; Stramaglia, Maria Elena; Strandberg, Jonas; Strandberg, Sara; Strandlie, Are; Strauss, Emanuel; Strauss, Michael; Strizenec, Pavol; Ströhmer, Raimund; Strom, David; Stroynowski, Ryszard; Strubig, Antonia; Stucci, Stefania Antonia; Stugu, Bjarne; Styles, Nicholas Adam; Su, Dong; Su, Jun; Subramaniam, Rajivalochan; Succurro, Antonella; Sugaya, Yorihito; Suhr, Chad; Suk, Michal; Sulin, Vladimir; Sultansoy, Saleh; Sumida, Toshi; Sun, Siyuan; Sun, Xiaohu; Sundermann, Jan Erik; Suruliz, Kerim; Susinno, Giancarlo; Sutton, Mark; Suzuki, Shota; Suzuki, Yu; Svatos, Michal; Swedish, Stephen; Swiatlowski, Maximilian; Sykora, Ivan; Sykora, Tomas; Ta, Duc; Taccini, Cecilia; Tackmann, Kerstin; Taenzer, Joe; Taffard, Anyes; Tafirout, Reda; Taiblum, Nimrod; Takai, Helio; Takashima, Ryuichi; Takeda, Hiroshi; Takeshita, Tohru; Takubo, Yosuke; Talby, Mossadek; Talyshev, Alexey; Tam, Jason; Tan, Kong Guan; Tanaka, Junichi; Tanaka, Reisaburo; Tanaka, Satoshi; Tanaka, Shuji; Tannenwald, Benjamin Bordy; Tannoury, Nancy; Tapprogge, Stefan; Tarem, Shlomit; Tarrade, Fabien; Tartarelli, Giuseppe Francesco; Tas, Petr; Tasevsky, Marek; Tashiro, Takuya; Tassi, Enrico; Tavares Delgado, Ademar; Tayalati, Yahya; Taylor, Frank; Taylor, Geoffrey; Taylor, Wendy; Teischinger, Florian Alfred; Teixeira Dias Castanheira, Matilde; Teixeira-Dias, Pedro; Temming, Kim Katrin; Ten Kate, Herman; Teng, Ping-Kun; Teoh, Jia Jian; Tepel, Fabian-Phillipp; Terada, Susumu; Terashi, Koji; Terron, Juan; Terzo, Stefano; Testa, Marianna; Teuscher, Richard; Therhaag, Jan; Theveneaux-Pelzer, Timothée; Thomas, Juergen; Thomas-Wilsker, Joshuha; Thompson, Emily; Thompson, Paul; Thompson, Ray; Thompson, Stan; Thomsen, Lotte Ansgaard; Thomson, Evelyn; Thomson, Mark; Thun, Rudolf; Tibbetts, Mark James; Ticse Torres, Royer Edson; Tikhomirov, Vladimir; Tikhonov, Yury; Timoshenko, Sergey; Tiouchichine, Elodie; Tipton, Paul; Tisserant, Sylvain; Todorov, Theodore; Todorova-Nova, Sharka; Tojo, Junji; Tokár, Stanislav; Tokushuku, Katsuo; Tollefson, Kirsten; Tolley, Emma; Tomlinson, Lee; Tomoto, Makoto; Tompkins, Lauren; Toms, Konstantin; Torrence, Eric; Torres, Heberth; Torró Pastor, Emma; Toth, Jozsef; Touchard, Francois; Tovey, Daniel; Trefzger, Thomas; Tremblet, Louis; Tricoli, Alessandro; Trigger, Isabel Marian; Trincaz-Duvoid, Sophie; Tripiana, Martin; Trischuk, William; Trocmé, Benjamin; Troncon, Clara; Trottier-McDonald, Michel; Trovatelli, Monica; True, Patrick; Trzebinski, Maciej; Trzupek, Adam; Tsarouchas, Charilaos; Tseng, Jeffrey; Tsiareshka, Pavel; Tsionou, Dimitra; Tsipolitis, Georgios; Tsirintanis, Nikolaos; Tsiskaridze, Shota; Tsiskaridze, Vakhtang; Tskhadadze, Edisher; Tsukerman, Ilya; Tsulaia, Vakhtang; Tsuno, Soshi; Tsybychev, Dmitri; Tudorache, Alexandra; Tudorache, Valentina; Tuna, Alexander Naip; Tupputi, Salvatore; Turchikhin, Semen; Turecek, Daniel; Turra, Ruggero; Turvey, Andrew John; Tuts, Michael; Tykhonov, Andrii; Tylmad, Maja; Tyndel, Mike; Ueda, Ikuo; Ueno, Ryuichi; Ughetto, Michael; Ugland, Maren; Uhlenbrock, Mathias; Ukegawa, Fumihiko; Unal, Guillaume; Undrus, Alexander; Unel, Gokhan; Ungaro, Francesca; Unno, Yoshinobu; Unverdorben, Christopher; Urban, Jozef; Urquijo, Phillip; Urrejola, Pedro; Usai, Giulio; Usanova, Anna; Vacavant, Laurent; Vacek, Vaclav; Vachon, Brigitte; Valderanis, Chrysostomos; Valencic, Nika; Valentinetti, Sara; Valero, Alberto; Valery, Loic; Valkar, Stefan; Valladolid Gallego, Eva; Vallecorsa, Sofia; Valls Ferrer, Juan Antonio; Van Den Wollenberg, Wouter; Van Der Deijl, Pieter; van der Geer, Rogier; van der Graaf, Harry; Van Der Leeuw, Robin; van Eldik, Niels; van Gemmeren, Peter; Van Nieuwkoop, Jacobus; van Vulpen, Ivo; van Woerden, Marius Cornelis; Vanadia, Marco; Vandelli, Wainer; Vanguri, Rami; Vaniachine, Alexandre; Vannucci, Francois; Vardanyan, Gagik; Vari, Riccardo; Varnes, Erich; Varol, Tulin; Varouchas, Dimitris; Vartapetian, Armen; Varvell, Kevin; Vazeille, Francois; Vazquez Schroeder, Tamara; Veatch, Jason; Veloso, Filipe; Velz, Thomas; Veneziano, Stefano; Ventura, Andrea; Ventura, Daniel; Venturi, Manuela; Venturi, Nicola; Venturini, Alessio; Vercesi, Valerio; Verducci, Monica; Verkerke, Wouter; Vermeulen, Jos; Vest, Anja; Vetterli, Michel; Viazlo, Oleksandr; Vichou, Irene; Vickey, Trevor; Vickey Boeriu, Oana Elena; Viehhauser, Georg; Viel, Simon; Vigne, Ralph; Villa, Mauro; Villaplana Perez, Miguel; Vilucchi, Elisabetta; Vincter, Manuella; Vinogradov, Vladimir; Vivarelli, Iacopo; Vives Vaque, Francesc; Vlachos, Sotirios; Vladoiu, Dan; Vlasak, Michal; Vogel, Marcelo; Vokac, Petr; Volpi, Guido; Volpi, Matteo; von der Schmitt, Hans; von Radziewski, Holger; von Toerne, Eckhard; Vorobel, Vit; Vorobev, Konstantin; Vos, Marcel; Voss, Rudiger; Vossebeld, Joost; Vranjes, Nenad; Vranjes Milosavljevic, Marija; Vrba, Vaclav; Vreeswijk, Marcel; Vuillermet, Raphael; Vukotic, Ilija; Vykydal, Zdenek; Wagner, Peter; Wagner, Wolfgang; Wahlberg, Hernan; Wahrmund, Sebastian; Wakabayashi, Jun; Walder, James; Walker, Rodney; Walkowiak, Wolfgang; Wang, Chao; Wang, Fuquan; Wang, Haichen; Wang, Hulin; Wang, Jike; Wang, Jin; Wang, Kuhan; Wang, Rui; Wang, Song-Ming; Wang, Tan; Wang, Xiaoxiao; Wanotayaroj, Chaowaroj; Warburton, Andreas; Ward, Patricia; Wardrope, David Robert; Warsinsky, Markus; Washbrook, Andrew; Wasicki, Christoph; Watkins, Peter; Watson, Alan; Watson, Ian; Watson, Miriam; Watts, Gordon; Watts, Stephen; Waugh, Ben; Webb, Samuel; Weber, Michele; Weber, Stefan Wolf; Webster, Jordan S; Weidberg, Anthony; Weinert, Benjamin; Weingarten, Jens; Weiser, Christian; Weits, Hartger; Wells, Phillippa; Wenaus, Torre; Wengler, Thorsten; Wenig, Siegfried; Wermes, Norbert; Werner, Matthias; Werner, Per; Wessels, Martin; Wetter, Jeffrey; Whalen, Kathleen; Wharton, Andrew Mark; White, Andrew; White, Martin; White, Ryan; White, Sebastian; Whiteson, Daniel; Wickens, Fred; Wiedenmann, Werner; Wielers, Monika; Wienemann, Peter; Wiglesworth, Craig; Wiik-Fuchs, Liv Antje Mari; Wildauer, Andreas; Wilkens, Henric George; Williams, Hugh; Williams, Sarah; Willis, Christopher; Willocq, Stephane; Wilson, Alan; Wilson, John; Wingerter-Seez, Isabelle; Winklmeier, Frank; Winter, Benedict Tobias; Wittgen, Matthias; Wittkowski, Josephine; Wollstadt, Simon Jakob; Wolter, Marcin Wladyslaw; Wolters, Helmut; Wosiek, Barbara; Wotschack, Jorg; Woudstra, Martin; Wozniak, Krzysztof; Wu, Mengqing; Wu, Miles; Wu, Sau Lan; Wu, Xin; Wu, Yusheng; Wyatt, Terry Richard; Wynne, Benjamin; Xella, Stefania; Xu, Da; Xu, Lailin; Yabsley, Bruce; Yacoob, Sahal; Yakabe, Ryota; Yamada, Miho; Yamaguchi, Yohei; Yamamoto, Akira; Yamamoto, Shimpei; Yamanaka, Takashi; Yamauchi, Katsuya; Yamazaki, Yuji; Yan, Zhen; Yang, Haijun; Yang, Hongtao; Yang, Yi; Yao, Liwen; Yao, Weiming; Yasu, Yoshiji; Yatsenko, Elena; Yau Wong, Kaven Henry; Ye, Jingbo; Ye, Shuwei; Yeletskikh, Ivan; Yen, Andy L; Yildirim, Eda; Yorita, Kohei; Yoshida, Rikutaro; Yoshihara, Keisuke; Young, Charles; Young, Christopher John; Youssef, Saul; Yu, David Ren-Hwa; Yu, Jaehoon; Yu, Jiaming; Yu, Jie; Yuan, Li; Yurkewicz, Adam; Yusuff, Imran; Zabinski, Bartlomiej; Zaidan, Remi; Zaitsev, Alexander; Zalieckas, Justas; Zaman, Aungshuman; Zambito, Stefano; Zanello, Lucia; Zanzi, Daniele; Zeitnitz, Christian; Zeman, Martin; Zemla, Andrzej; Zengel, Keith; Zenin, Oleg; Ženiš, Tibor; Zerwas, Dirk; Zhang, Dongliang; Zhang, Fangzhou; Zhang, Jinlong; Zhang, Lei; Zhang, Ruiqi; Zhang, Xueyao; Zhang, Zhiqing; Zhao, Xiandong; Zhao, Yongke; Zhao, Zhengguo; Zhemchugov, Alexey; Zhong, Jiahang; Zhou, Bing; Zhou, Chen; Zhou, Lei; Zhou, Li; Zhou, Ning; Zhu, Cheng Guang; Zhu, Hongbo; Zhu, Junjie; Zhu, Yingchun; Zhuang, Xuai; Zhukov, Konstantin; Zibell, Andre; Zieminska, Daria; Zimine, Nikolai; Zimmermann, Christoph; Zimmermann, Robert; Zimmermann, Stephanie; Zinonos, Zinonas; Zinser, Markus; Ziolkowski, Michael; Živković, Lidija; Zobernig, Georg; Zoccoli, Antonio; zur Nedden, Martin; Zurzolo, Giovanni; Zwalinski, Lukasz

    2015-07-17

    Measurements of the $ZZ$ and $WW$ final states in the mass range above the $2m_Z$ and $2m_W$ thresholds provide a unique opportunity to measure the off-shell coupling strength of the Higgs boson. This paper presents a determination of the off-shell Higgs boson event yields normalised to the Standard Model prediction (signal strength) in the $ZZ \\rightarrow 4\\ell$, $ZZ\\rightarrow 2\\ell2\

  12. Signal-to-noise ratio and detective quantum efficiency determination by and alternative use of photographic detectors

    International Nuclear Information System (INIS)

    Burgudzhiev, Z.; Koleva, D.

    1986-01-01

    A known theoretical model of an alternative use of silver-halogenid pnotographic emulsions in which the number of the granulas forming the photographic image is used as a detector output instead of the microdensiometric blackening density is applied to some real photographic emulsions. It is found that by this use the Signal-to-Noise ratio of the photographic detector can be increased to about 5 times while its detective quantum efficiency can reach about 20%, being close to that of some photomultipliers

  13. Determination of Tobramycin in M9 Medium by LC-MS/MS: Signal Enhancement by Trichloroacetic Acid

    DEFF Research Database (Denmark)

    Huang, Liusheng; Haagensen, Janus Anders Juul; Verotta, Davide

    2018-01-01

    mM ammonium formate and 0.14% trifluoroacetic acid and acetonitrile containing 0.1% trifluoroacetic acid in a gradient mode. ESI+ and MRM with ion m/z 468 → 324 for tobramycin and m/z 473 -> 327 for the IS were used for quantification. The calibration curve concentration range was 50-25000 ng....../mL. Matrix effect from M9 media was not significant when compared with injection solvents, but signal enhancement by trichloroacetic acid was significant (∼ 3 fold). The method is simple, fast, and reliable. Using the method, the in vitro PK/PD model was tested with one bolus dose of tobramycin....

  14. Flavonoids from Lonchocarpus araripensis (Leguminoseae): isolation, unequivocal assignment of NMR signals {sup 1}H and {sup 13}C and conformational analysis; Flavonoides de Lonchocarpus araripensis (Leguminoseae): isolamento, atribuicao inequivoca dos sinais de RMN {sup 1}H e {sup 13}C e analise conformacional

    Energy Technology Data Exchange (ETDEWEB)

    Lima, Almi F.; Ferreira, Daniele A.; Monte, Francisco Jose Q., E-mail: fmonte@dqoi.ufc.br [Universidade Federal do Ceara (UFC), Fortaleza, CE (Brazil). Centro de Ciencias. Departamento de Quimica Organica e Inorganica; Braz-Filho, Raimundo [Universidade Estadual do Norte Fluminense (UENF), Campo dos Goytacazes, RJ (Brazil). Centro de Ciencias Tecnologicas. Laboratorio de Ciencias Quimicas

    2014-07-01

    In a continuing investigation for potentially bioactive natural products, flavonoids were isolated from Lonchocarpus araripensis (Leguminoseae) and identified as 3-methoxy-6-O-prenyl-6'',6''-dimethylchromene-[7,8,2'',3'']-flavone (1), 3,6-dimethoxy-6'',6''-dimethylchromene-[7,8,2'',3'']-flavone (2) and 3,5,8-trimethoxy-[6,7,2{sup ,}3{sup ]}-furanoflavone (3). This is the first time compound 3 has been described. Compound 2 has been previously isolated from roots while this is the first time 1 is reported in this species. Complete NMR assignments are given for 1 ,2 and 3 together with the determination of conformation for 1. (author)

  15. Structural determination of importin alpha in complex with beak and feather disease virus capsid nuclear localization signal

    International Nuclear Information System (INIS)

    Patterson, Edward I.; Dombrovski, Andrew K.; Swarbrick, Crystall M.D.; Raidal, Shane R.; Forwood, Jade K.

    2013-01-01

    Highlights: •Circovirus capsid proteins contain large nuclear localization signals (NLS). •A method of nuclear import has not been elucidated. •Beak and feather disease virus (BFDV) capsid NLS was crystallized with importin α. •The structure showed BFDV NLS binding to the major site of importin α. •Result shows implications for mechanism of nuclear transport for all circoviruses. -- Abstract: Circoviruses represent a rapidly increasing genus of viruses that infect a variety of vertebrates. Replication requires shuttling viral molecules into the host cell nucleus, a process facilitated by capsid-associated protein (Cap). Whilst a nuclear localization signal (NLS) has been shown to mediate nuclear translocation, the mode of nuclear transport remains to be elucidated. To better understand this process, beak and feather disease virus (BFDV) Cap NLS was crystallized with nuclear import receptor importin-α (Impα). Diffraction yielded structural data to 2.9 Å resolution, and the binding site on both Impα and BFDV Cap NLS were well resolved. The binding mechanism for the major site is likely conserved across circoviruses as supported by the similarity of NLSs in circovirus Caps. This finding illuminates a crucial step for infection of host cells by this viral family, and provides a platform for rational drug design against the binding interface

  16. Persistence and dynamics of DNA damage signal amplification determined by microcolony formation and live-cell imaging

    International Nuclear Information System (INIS)

    Oka, Yasuyoshi; Yamauchi, Motohiro; Suzuki, Masatoshi; Yamashita, Shunichi; Suzuki, Keiji

    2011-01-01

    Cell cycle checkpoints are essential cellular process protecting the integrity of the genome from DNA damaging agents. In the present study, we developed a microcolony assay, in which normal human diploid fibroblast-like cells exposed to ionizing radiation, were plated onto coverslips at very low density (3 cells/cm 2 ). Cells were grown for up to 3 days, and phosphorylated ataxia-telangiectasia mutated (ATM) at Ser1981 and 53BP1 foci were analyzed as the markers for an amplified DNA damage signal. We observed a dose-dependent increase in the fraction of non-dividing cells, whose increase was compromised by knocking down p53 expression. While large persistent foci were predominantly formed in non-dividing cells, we observed some growing colonies that contained cells with large foci. As each microcolony was derived from a single cell, it appeared that some cells could proliferate with large foci. A live-imaging analysis using hTERT-immortalized normal human diploid cells transfected with the EGFP-tagged 53BP1 gene revealed that the formation of persistent large foci was highly dynamic. Delayed appearance and disappearance of large foci were frequently observed in exposed cells visualized 12-72 hours after X-irradiation. Thus, our results indicate that amplified DNA damage signal could be ignored, which may be explained in part by the dynamic nature of the amplification process. (author)

  17. Loss of Mitogen-Activated Protein Kinase Kinase Kinase 4 (MAP3K4) Reveals a Requirement for MAPK Signalling in Mouse Sex Determination

    Science.gov (United States)

    Bogani, Debora; Siggers, Pam; Brixey, Rachel; Warr, Nick; Beddow, Sarah; Edwards, Jessica; Williams, Debbie; Wilhelm, Dagmar; Koopman, Peter; Flavell, Richard A.; Chi, Hongbo; Ostrer, Harry; Wells, Sara; Cheeseman, Michael; Greenfield, Andy

    2009-01-01

    Sex determination in mammals is controlled by the presence or absence of the Y-linked gene SRY. In the developing male (XY) gonad, sex-determining region of the Y (SRY) protein acts to up-regulate expression of the related gene, SOX9, a transcriptional regulator that in turn initiates a downstream pathway of testis development, whilst also suppressing ovary development. Despite the requirement for a number of transcription factors and secreted signalling molecules in sex determination, intracellular signalling components functioning in this process have not been defined. Here we report a role for the phylogenetically ancient mitogen-activated protein kinase (MAPK) signalling pathway in mouse sex determination. Using a forward genetic screen, we identified the recessive boygirl (byg) mutation. On the C57BL/6J background, embryos homozygous for byg exhibit consistent XY gonadal sex reversal. The byg mutation is an A to T transversion causing a premature stop codon in the gene encoding MAP3K4 (also known as MEKK4), a mitogen-activated protein kinase kinase kinase. Analysis of XY byg/byg gonads at 11.5 d post coitum reveals a growth deficit and a failure to support mesonephric cell migration, both early cellular processes normally associated with testis development. Expression analysis of mutant XY gonads at the same stage also reveals a dramatic reduction in Sox9 and, crucially, Sry at the transcript and protein levels. Moreover, we describe experiments showing the presence of activated MKK4, a direct target of MAP3K4, and activated p38 in the coelomic region of the XY gonad at 11.5 d post coitum, establishing a link between MAPK signalling in proliferating gonadal somatic cells and regulation of Sry expression. Finally, we provide evidence that haploinsufficiency for Map3k4 accounts for T-associated sex reversal (Tas). These data demonstrate that MAP3K4-dependent signalling events are required for normal expression of Sry during testis development, and create a novel

  18. Loss of mitogen-activated protein kinase kinase kinase 4 (MAP3K4 reveals a requirement for MAPK signalling in mouse sex determination.

    Directory of Open Access Journals (Sweden)

    Debora Bogani

    2009-09-01

    Full Text Available Sex determination in mammals is controlled by the presence or absence of the Y-linked gene SRY. In the developing male (XY gonad, sex-determining region of the Y (SRY protein acts to up-regulate expression of the related gene, SOX9, a transcriptional regulator that in turn initiates a downstream pathway of testis development, whilst also suppressing ovary development. Despite the requirement for a number of transcription factors and secreted signalling molecules in sex determination, intracellular signalling components functioning in this process have not been defined. Here we report a role for the phylogenetically ancient mitogen-activated protein kinase (MAPK signalling pathway in mouse sex determination. Using a forward genetic screen, we identified the recessive boygirl (byg mutation. On the C57BL/6J background, embryos homozygous for byg exhibit consistent XY gonadal sex reversal. The byg mutation is an A to T transversion causing a premature stop codon in the gene encoding MAP3K4 (also known as MEKK4, a mitogen-activated protein kinase kinase kinase. Analysis of XY byg/byg gonads at 11.5 d post coitum reveals a growth deficit and a failure to support mesonephric cell migration, both early cellular processes normally associated with testis development. Expression analysis of mutant XY gonads at the same stage also reveals a dramatic reduction in Sox9 and, crucially, Sry at the transcript and protein levels. Moreover, we describe experiments showing the presence of activated MKK4, a direct target of MAP3K4, and activated p38 in the coelomic region of the XY gonad at 11.5 d post coitum, establishing a link between MAPK signalling in proliferating gonadal somatic cells and regulation of Sry expression. Finally, we provide evidence that haploinsufficiency for Map3k4 accounts for T-associated sex reversal (Tas. These data demonstrate that MAP3K4-dependent signalling events are required for normal expression of Sry during testis development, and

  19. Supersymmetric Yang-Mills theory on conformal supergravity backgrounds in ten dimensions

    Energy Technology Data Exchange (ETDEWEB)

    Medeiros, Paul de; Figueroa-O’Farrill, José [Maxwell Institute and School of Mathematics, The University of Edinburgh,James Clerk Maxwell Building, Peter Guthrie Tait Road, Edinburgh EH9 3FD (United Kingdom)

    2016-03-14

    We consider bosonic supersymmetric backgrounds of ten-dimensional conformal supergravity. Up to local conformal isometry, we classify the maximally supersymmetric backgrounds, determine their conformal symmetry superalgebras and show how they arise as near-horizon geometries of certain half-BPS backgrounds or as a plane-wave limit thereof. We then show how to define Yang-Mills theory with rigid supersymmetry on any supersymmetric conformal supergravity background and, in particular, on the maximally supersymmetric backgrounds. We conclude by commenting on a striking resemblance between the supersymmetric backgrounds of ten-dimensional conformal supergravity and those of eleven-dimensional Poincaré supergravity.

  20. Conformal invariance and conserved quantities of Appell systems under second-class Mei symmetry

    International Nuclear Information System (INIS)

    Yi-Ping, Luo; Jing-Li, Fu

    2010-01-01

    In this paper we introduce the new concept of the conformal invariance and the conserved quantities for Appell systems under second-class Mei symmetry. The one-parameter infinitesimal transformation group and infinitesimal transformation vector of generator are described in detail. The conformal factor in the determining equations under second-class Mei symmetry is found. The relationship between Appell system's conformal invariance and Mei symmetry are discussed. And Appell system's conformal invariance under second-class Mei symmetry may lead to corresponding Hojman conserved quantities when the conformal invariance satisfies some conditions. Lastly, an example is provided to illustrate the application of the result. (general)

  1. Deep Inelastic Scattering in Conformal QCD

    CERN Document Server

    Cornalba, Lorenzo; Penedones, Joao

    2010-01-01

    We consider the Regge limit of a CFT correlation function of two vector and two scalar operators, as appropriate to study small-x deep inelastic scattering in N=4 SYM or in QCD assuming approximate conformal symmetry. After clarifying the nature of the Regge limit for a CFT correlator, we use its conformal partial wave expansion to obtain an impact parameter representation encoding the exchange of a spin j Reggeon for any value of the coupling constant. The CFT impact parameter space is the three-dimensional hyperbolic space H3, which is the impact parameter space for high energy scattering in the dual AdS space. We determine the small-x structure functions associated to the exchange of a Reggeon. We discuss unitarization from the point of view of scattering in AdS and comment on the validity of the eikonal approximation. We then focus on the weak coupling limit of the theory where the amplitude is dominated by the exchange of the BFKL pomeron. Conformal invariance fixes the form of the vector impact factor a...

  2. Gauge fixing problem in the conformal QED

    International Nuclear Information System (INIS)

    Ichinose, Shoichi

    1986-01-01

    The gauge fixing problem in the conformal (spinor and scalar) QED is examined. For the analysis, we generalize Dirac's manifestly conformal-covariant formalism. It is shown that the (vector and matter) fields must obey a certain mixed (conformal and gauge) type of transformation law in order to fix the local gauge symmetry preserving the conformal invariance in the Lagrangian. (orig.)

  3. Simultaneous determination of effective carrier lifetime and resistivity of Si wafers using the nonlinear nature of photocarrier radiometric signals

    Science.gov (United States)

    Sun, Qiming; Melnikov, Alexander; Wang, Jing; Mandelis, Andreas

    2018-04-01

    A rigorous treatment of the nonlinear behavior of photocarrier radiometric (PCR) signals is presented theoretically and experimentally for the quantitative characterization of semiconductor photocarrier recombination and transport properties. A frequency-domain model based on the carrier rate equation and the classical carrier radiative recombination theory was developed. The derived concise expression reveals different functionalities of the PCR amplitude and phase channels: the phase bears direct quantitative correlation with the carrier effective lifetime, while the amplitude versus the estimated photocarrier density dependence can be used to extract the equilibrium majority carrier density and thus, resistivity. An experimental ‘ripple’ optical excitation mode (small modulation depth compared to the dc level) was introduced to bypass the complicated ‘modulated lifetime’ problem so as to simplify theoretical interpretation and guarantee measurement self-consistency and reliability. Two Si wafers with known resistivity values were tested to validate the method.

  4. Conformational Study of Taurine in the Gas Phase

    Science.gov (United States)

    Cortijo, Vanessa; Sanz, M. Eugenia; López, Juan C.; Alonso, José L.

    2009-08-01

    The conformational preferences of the amino sulfonic acid taurine (NH2-CH2-CH2-SO3H) have been investigated in the gas phase by laser ablation molecular beam Fourier transform microwave spectroscopy (LA-MB-FTMW) in the 6-14 GHz frequency range. One conformer has been observed, and its rotational, centrifugal distortion, and hyperfine quadrupole coupling constants have been determined from the analysis of its rotational spectrum. Comparison of the experimental constants with those calculated theoretically identifies the detected conformer unambiguously. The observed conformer of taurine is stabilized by an intramolecular hydrogen bond O-H···N between the hydrogen of the sulfonic acid group and the nitrogen atom of the amino group.

  5. DOA Estimation of Cylindrical Conformal Array Based on Geometric Algebra

    Directory of Open Access Journals (Sweden)

    Minjie Wu

    2016-01-01

    Full Text Available Due to the variable curvature of the conformal carrier, the pattern of each element has a different direction. The traditional method of analyzing the conformal array is to use the Euler rotation angle and its matrix representation. However, it is computationally demanding especially for irregular array structures. In this paper, we present a novel algorithm by combining the geometric algebra with Multiple Signal Classification (MUSIC, termed as GA-MUSIC, to solve the direction of arrival (DOA for cylindrical conformal array. And on this basis, we derive the pattern and array manifold. Compared with the existing algorithms, our proposed one avoids the cumbersome matrix transformations and largely decreases the computational complexity. The simulation results verify the effectiveness of the proposed method.

  6. The Large-scale Effect of Environment on Galactic Conformity

    Science.gov (United States)

    Sun, Shuangpeng; Guo, Qi; Wang, Lan; Wang, Jie; Gao, Liang; Lacey, Cedric G.; Pan, Jun

    2018-04-01

    We use a volume-limited galaxy sample from the SDSS Data Release 7 to explore the dependence of galactic conformity on the large-scale environment, measured on ˜ 4 Mpc scales. We find that the star formation activity of neighbour galaxies depends more strongly on the environment than on the activity of their primary galaxies. In under-dense regions most neighbour galaxies tend to be active, while in over-dense regions neighbour galaxies are mostly passive, regardless of the activity of their primary galaxies. At a given stellar mass, passive primary galaxies reside in higher density regions than active primary galaxies, leading to the apparently strong conformity signal. The dependence of the activity of neighbour galaxies on environment can be explained by the corresponding dependence of the fraction of satellite galaxies. Similar results are found for galaxies in a semi-analytical model, suggesting that no new physics is required to explain the observed large-scale conformity.

  7. Renyi entropy and conformal defects

    Energy Technology Data Exchange (ETDEWEB)

    Bianchi, Lorenzo [Humboldt-Univ. Berlin (Germany). Inst. fuer Physik; Hamburg Univ. (Germany). II. Inst. fuer Theoretische Physik; Meineri, Marco [Scuola Normale Superiore, Pisa (Italy); Perimeter Institute for Theoretical Physics, Waterloo, ON (Canada); Istituto Nazionale di Fisica Nucleare, Pisa (Italy); Myers, Robert C. [Perimeter Institute for Theoretical Physics, Waterloo, ON (Canada); Smolkin, Michael [California Univ., Berkely, CA (United States). Center for Theoretical Physics and Department of Physics

    2016-04-18

    We propose a field theoretic framework for calculating the dependence of Renyi entropies on the shape of the entangling surface in a conformal field theory. Our approach rests on regarding the corresponding twist operator as a conformal defect and in particular, we define the displacement operator which implements small local deformations of the entangling surface. We identify a simple constraint between the coefficient defining the two-point function of the displacement operator and the conformal weight of the twist operator, which consolidates a number of distinct conjectures on the shape dependence of the Renyi entropy. As an example, using this approach, we examine a conjecture regarding the universal coefficient associated with a conical singularity in the entangling surface for CFTs in any number of spacetime dimensions. We also provide a general formula for the second order variation of the Renyi entropy arising from small deformations of a spherical entangling surface, extending Mezei's results for the entanglement entropy.

  8. Conformal dimension theory and application

    CERN Document Server

    Mackay, John M

    2010-01-01

    Conformal dimension measures the extent to which the Hausdorff dimension of a metric space can be lowered by quasisymmetric deformations. Introduced by Pansu in 1989, this concept has proved extremely fruitful in a diverse range of areas, including geometric function theory, conformal dynamics, and geometric group theory. This survey leads the reader from the definitions and basic theory through to active research applications in geometric function theory, Gromov hyperbolic geometry, and the dynamics of rational maps, amongst other areas. It reviews the theory of dimension in metric spaces and of deformations of metric spaces. It summarizes the basic tools for estimating conformal dimension and illustrates their application to concrete problems of independent interest. Numerous examples and proofs are provided. Working from basic definitions through to current research areas, this book can be used as a guide for graduate students interested in this field, or as a helpful survey for experts. Background needed ...

  9. Elementary introduction to conformal invariance

    International Nuclear Information System (INIS)

    Grandati, Y.

    1992-01-01

    These notes constitute an elementary introduction to the concept of conformal invariance and its applications to the study of bidimensional critical phenomena. The aim is to give an access as pedestrian as possible to this vast subject. After a brief account of the general properties of conformal transformation in D dimensions, we study more specifically the case D = 2. The center of the discussion is then the consequences of the action of this symmetry group on bidimensional field theories, and in particular the links between the representations of the Virasoro algebra and the structure of the correlation functions of conformal field theories. Finally after showing how the Ising model reduces to a Majorana fermionic field theory, we see how the general formalism previously discussed can be applied to the Ising case at the critical point. (orig.)

  10. Conformal geometry and quasiregular mappings

    CERN Document Server

    Vuorinen, Matti

    1988-01-01

    This book is an introduction to the theory of spatial quasiregular mappings intended for the uninitiated reader. At the same time the book also addresses specialists in classical analysis and, in particular, geometric function theory. The text leads the reader to the frontier of current research and covers some most recent developments in the subject, previously scatterd through the literature. A major role in this monograph is played by certain conformal invariants which are solutions of extremal problems related to extremal lengths of curve families. These invariants are then applied to prove sharp distortion theorems for quasiregular mappings. One of these extremal problems of conformal geometry generalizes a classical two-dimensional problem of O. Teichmüller. The novel feature of the exposition is the way in which conformal invariants are applied and the sharp results obtained should be of considerable interest even in the two-dimensional particular case. This book combines the features of a textbook an...

  11. Renyi entropy and conformal defects

    International Nuclear Information System (INIS)

    Bianchi, Lorenzo; Myers, Robert C.; Smolkin, Michael

    2016-01-01

    We propose a field theoretic framework for calculating the dependence of Renyi entropies on the shape of the entangling surface in a conformal field theory. Our approach rests on regarding the corresponding twist operator as a conformal defect and in particular, we define the displacement operator which implements small local deformations of the entangling surface. We identify a simple constraint between the coefficient defining the two-point function of the displacement operator and the conformal weight of the twist operator, which consolidates a number of distinct conjectures on the shape dependence of the Renyi entropy. As an example, using this approach, we examine a conjecture regarding the universal coefficient associated with a conical singularity in the entangling surface for CFTs in any number of spacetime dimensions. We also provide a general formula for the second order variation of the Renyi entropy arising from small deformations of a spherical entangling surface, extending Mezei's results for the entanglement entropy.

  12. Energy determination of cosmic ray showers in surface arrays using signal inference at a single distance from the core

    Energy Technology Data Exchange (ETDEWEB)

    Ros, G. [Space Plasmas and AStroparticle Group, Dpto. Fisica, Universidad de Alcala Ctra, Madrid-Barcelona km. 33, Alcala de Henares E-28871 (Spain)], E-mail: germanrosmagan@yahoo.es; Medina-Tanco, G. [Instituto de Ciencias Nucleares, UNAM, Circuito Exteriror S/N, Ciudad Universitaria, Mexico D. F. 04510 (Mexico); Peral, L. del [Space Plasmas and AStroparticle Group, Dpto. Fisica, Universidad de Alcala Ctra, Madrid-Barcelona km. 33, Alcala de Henares E-28871 (Spain); D' Olivo, J.C. [Instituto de Ciencias Nucleares, UNAM, Circuito Exteriror S/N, Ciudad Universitaria, Mexico D. F. 04510 (Mexico); Arqueros, F. [Dpto. Fisica Atomica, Molecular y Nuclear, Facultad de Fisica, Universidad Complutense de Madrid, Ciudad Universitaria 28040, Madrid (Spain); Rodriguez-Frias, M.D. [Space Plasmas and AStroparticle Group, Dpto. Fisica, Universidad de Alcala Ctra, Madrid-Barcelona km. 33, Alcala de Henares E-28871 (Spain)

    2009-09-21

    In most high energy cosmic ray surface arrays, the primary energy is currently determined from the value of the lateral distribution function at a fixed distance from the shower core, r{sub 0}. The value of r{sub 0} is mainly related to the geometry of the array and is, therefore, considered as fixed independently of the shower energy or direction. We argue, however, that the dependence of r{sub 0} on energy and zenith angle is not negligible. Therefore, in the present work we propose a new characteristic distance, which we call r{sub opt}, specifically determined for each individual shower, with the objective of optimizing the energy reconstruction. This parameter may not only improve the energy determination, but also allow a more reliable reconstruction of the shape and position of rapidly varying spectral features. We show that the use of a specific r{sub opt} determined on a shower-to-shower basis, instead of using a fixed characteristic value, is of particular benefit in dealing with the energy reconstruction of events with saturated detectors, which are in general a large fraction of all the events detected by an array as energy increases. Furthermore, the r{sub opt} approach has the additional advantage of applying the same unified treatment for all detected events, regardless of whether they have saturated detectors or not.

  13. Basal-subtype and MEK-Pl3K feedback signaling determine susceptibility of breast cancer cells to MEK inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Mirzoeva, Olga K.; Das, Debopriya; Heiser, Laura M.; Bhattacharya, Sanchita; Siwak, Doris; Gendelman, Rina; Bayani, Nora; Wang, Nicholas J.; Neve, Richard M.; Knight, Zachary; Feiler, Heidi S.; Gascard, Philippe; Parvin, Bahram; Spellman, Paul T.; Shokat, Kevan M.; Wyrobek, Andrew J.; Bissell, Mina J.; McCormick, Frank; Kuo, Wen-Lin; Mills, Gordon B.; Gray, Joe W.; Korn, W. Michael

    2009-01-23

    Specific inhibitors of MEK have been developed that efficiently inhibit the oncogenic RAF-MEK-ERK pathway. We employed a systems-based approach to identify breast cancer subtypes particularly susceptible to MEK inhibitors and to understand molecular mechanisms conferring resistance to such compounds. Basal-type breast cancer cells were found to be particularly susceptible to growth-inhibition by small-molecule MEK inhibitors. Activation of the PI3 kinase pathway in response to MEK inhibition through a negative MEK-EGFR-PI3 kinase feedback loop was found to limit efficacy. Interruption of this feedback mechanism by targeting MEK and PI3 kinase produced synergistic effects, including induction of apoptosis and, in some cell lines, cell cycle arrest and protection from apoptosis induced by proapoptotic agents. These findings enhance our understanding of the interconnectivity of oncogenic signal transduction circuits and have implications for the design of future clinical trials of MEK inhibitors in breast cancer by guiding patient selection and suggesting rational combination therapies.

  14. SUSY Unparticle and Conformal Sequestering

    Energy Technology Data Exchange (ETDEWEB)

    Nakayama, Yu; Nakayama, Yu

    2007-07-17

    We investigate unparticle physics with supersymmetry (SUSY). The SUSY breaking effects due to the gravity mediation induce soft masses for the SUSY unparticles and hence break the conformal invariance. The unparticle physics observable in near future experiments is only consistent if the SUSY breakingeffects from the hidden sector to the standard model sector are dominated by the gauge mediation, or if the SUSY breaking effects to the unparticle sector are sufficiently sequestered. We argue that the natural realization of the latter possibility is the conformal sequestering scenario.

  15. Epigenetic dominance of prion conformers.

    Directory of Open Access Journals (Sweden)

    Eri Saijo

    2013-10-01

    Full Text Available Although they share certain biological properties with nucleic acid based infectious agents, prions, the causative agents of invariably fatal, transmissible neurodegenerative disorders such as bovine spongiform encephalopathy, sheep scrapie, and human Creutzfeldt Jakob disease, propagate by conformational templating of host encoded proteins. Once thought to be unique to these diseases, this mechanism is now recognized as a ubiquitous means of information transfer in biological systems, including other protein misfolding disorders such as those causing Alzheimer's and Parkinson's diseases. To address the poorly understood mechanism by which host prion protein (PrP primary structures interact with distinct prion conformations to influence pathogenesis, we produced transgenic (Tg mice expressing different sheep scrapie susceptibility alleles, varying only at a single amino acid at PrP residue 136. Tg mice expressing ovine PrP with alanine (A at (OvPrP-A136 infected with SSBP/1 scrapie prions propagated a relatively stable (S prion conformation, which accumulated as punctate aggregates in the brain, and produced prolonged incubation times. In contrast, Tg mice expressing OvPrP with valine (V at 136 (OvPrP-V136 infected with the same prions developed disease rapidly, and the converted prion was comprised of an unstable (U, diffusely distributed conformer. Infected Tg mice co-expressing both alleles manifested properties consistent with the U conformer, suggesting a dominant effect resulting from exclusive conversion of OvPrP-V136 but not OvPrP-A136. Surprisingly, however, studies with monoclonal antibody (mAb PRC5, which discriminates OvPrP-A136 from OvPrP-V136, revealed substantial conversion of OvPrP-A136. Moreover, the resulting OvPrP-A136 prion acquired the characteristics of the U conformer. These results, substantiated by in vitro analyses, indicated that co-expression of OvPrP-V136 altered the conversion potential of OvPrP-A136 from the S to

  16. Topics in conformal field theory

    International Nuclear Information System (INIS)

    Kiritsis, E.B.

    1988-01-01

    In this work two major topics in Conformal Field Theory are discussed. First a detailed investigation of N = 2 Superconformal theories is presented. The structure of the representations of the N = 2 superconformal algebras is investigated and the character formulae are calculated. The general structure of N = 2 superconformal theories is elucidated and the operator algebra of the minimal models is derived. The first minimal system is discussed in more detail. Second, applications of the conformal techniques are studied in the Ashkin-Teller model. The c = 1 as well as the c = 1/2 critical lines are discussed in detail

  17. Spectra of conformal sigma models

    International Nuclear Information System (INIS)

    Tlapak, Vaclav

    2015-04-01

    In this thesis the spectra of conformal sigma models defined on (generalized) symmetric spaces are analysed. The spaces where sigma models are conformal without the addition of a Wess-Zumino term are supermanifolds, in other words spaces that include fermionic directions. After a brief review of the general construction of vertex operators and the background field expansion, we compute the diagonal terms of the one-loop anomalous dimensions of sigma models on semi-symmetric spaces. We find that the results are formally identical to the symmetric case. However, unlike for sigma models on symmetric spaces, off diagonal terms that lead to operator mixing are also present. These are not computed here. We then present a detailed analysis of the one-loop spectrum of the supersphere S 3 vertical stroke 2 sigma model as one of the simplest examples. The analysis illustrates the power and simplicity of the construction. We use this data to revisit a duality with the OSP(4 vertical stroke 2) Gross-Neveu model that was proposed by Candu and Saleur. With the help of a recent all-loop result for the anomalous dimension of (1)/(2)BPS operators of Gross-Neveu models, we are able to recover the entire zero-mode spectrum of the supersphere model. We also argue that the sigma model constraints and its equations of motion are implemented correctly in the Gross-Neveu model, including the one-loop data. The duality is further supported by a new all-loop result for the anomalous dimension of the ground states of the sigma model. However, higher-gradient operators cannot be completely recovered. It is possible that this discrepancy is related to a known instability of the sigma model. The instability of sigma models is due to symmetry preserving high-gradient operators that become relevant at arbitrarily small values of the coupling. This feature has been observed long ago in one-loop calculations of the O(N)-vector model and soon been realized to be a generic property of sigma models

  18. Quantum-chemical calculation of energies and spectral characteristics of conformers in derivatives of phenylphosphine

    International Nuclear Information System (INIS)

    Chuvashev, D.D.; Ratovskii, G.V.; Zakzhevskii, V.G.

    1987-01-01

    The phenylphosphines PhPX 2 calculated by the MNDO method are characterized by two potential minima corresponding to the bisector and gonal conformations. For X = Cl, F, and C=N the bisector conformer predominates considerably, but for X = H and CH 3 the populations of the conformers are approximately the same. The characteristics of the electron transitions of the conformers found, determined by the CNDO/S method, differ substantially, which makes it possible to analyze the conformational compositions of arylphosphines by means of UV spectroscopy. In excited ππ* states the gonal conformation is characterized by a substantial donor effect of the PX 2 group, whereas the bisector conformation gives a certain acceptor effect

  19. Determination of the critical bending speeds of a multy-rotor shaft from the vibration signal analysis

    Science.gov (United States)

    Crâştiu, I.; Nyaguly, E.; Deac, S.; Gozman-Pop, C.; Bârgău, A.; Bereteu, L.

    2018-01-01

    The purpose of this paper is the development and validation of an impulse excitation technique to determine flexural critical speeds of a single rotor shaft and multy-rotor shaft. The experimental measurement of the vibroacoustic response is carried out by using a condenser microphone as a transducer. By the means of Modal Analysis using Finite Element Method (FEM), the natural frequencies and shape modes of one rotor and three rotor specimens are determined. The vibration responses of the specimens, in simple supported conditions, are carried out using algorithms based on Fast Fourier Transform (FFT). To validate the results of the modal parameters estimated using Finite Element Analysis (FEA) these are compared with experimental ones.

  20. The Possible Role of Dentin as a Piezoelectric Signal Generator by Determining the Elec-tromechanical Coupling Factor of Dentin

    Directory of Open Access Journals (Sweden)

    Atabak Shahidi

    2011-08-01

    Full Text Available Introduction: This article aimed at calculation of the electromechanical coupling factor of dentin which is an indicator of the effectiveness with which a piezoelectric material converts electrical en-ergy into mechanical energy, or vice versa. The hypothesis: The electro-mechanical coupling factor of dentin was determined in mode 11 and 33 by calculating the ratio of the produced electrical energy to the stored elastic energy in dentin under applied pressure. This study showed that the electromechanical coupling factor of dentin was affected by the direction of the applied force and the moisture content of dentin. Also dentin was a weak electromechanical energy converter which might be categorized as a piezoelectric pressure sensor.Evaluation of the hypothesis: Determination of the electrome-chanical coupling factor of dentin and its other piezoelectric constants is essential to investigate the biologic role of piezoelectricity in tooth.

  1. Sequential injection titration method using second-order signals: determination of acidity in plant oils and biodiesel samples.

    Science.gov (United States)

    del Río, Vanessa; Larrechi, M Soledad; Callao, M Pilar

    2010-06-15

    A new concept of flow titration is proposed and demonstrated for the determination of total acidity in plant oils and biodiesel. We use sequential injection analysis (SIA) with a diode array spectrophotometric detector linked to chemometric tools such as multivariate curve resolution-alternating least squares (MCR-ALS). This system is based on the evolution of the basic specie of an acid-base indicator, alizarine, when it comes into contact with a sample that contains free fatty acids. The gradual pH change in the reactor coil due to diffusion and reaction phenomenona allows the sequential appearance of both species of the indicator in the detector coil, recording a data matrix for each sample. The SIA-MCR-ALS method helps to reduce the amounts of sample, the reagents and the time consumed. Each determination consumes 0.413ml of sample, 0.250ml of indicator and 3ml of carrier (ethanol) and generates 3.333ml of waste. The frequency of the analysis is high (12 samples h(-1) including all steps, i.e., cleaning, preparing and analysing). The utilized reagents are of common use in the laboratory and it is not necessary to use the reagents of perfect known concentration. The method was applied to determine acidity in plant oil and biodiesel samples. Results obtained by the proposed method compare well with those obtained by the official European Community method that is time consuming and uses large amounts of organic solvents.

  2. Src kinase conformational activation: thermodynamics, pathways, and mechanisms.

    Directory of Open Access Journals (Sweden)

    Sichun Yang

    2008-03-01

    Full Text Available Tyrosine kinases of the Src-family are large allosteric enzymes that play a key role in cellular signaling. Conversion of the kinase from an inactive to an active state is accompanied by substantial structural changes. Here, we construct a coarse-grained model of the catalytic domain incorporating experimental structures for the two stable states, and simulate the dynamics of conformational transitions in kinase activation. We explore the transition energy landscapes by constructing a structural network among clusters of conformations from the simulations. From the structural network, two major ensembles of pathways for the activation are identified. In the first transition pathway, we find a coordinated switching mechanism of interactions among the alphaC helix, the activation-loop, and the beta strands in the N-lobe of the catalytic domain. In a second pathway, the conformational change is coupled to a partial unfolding of the N-lobe region of the catalytic domain. We also characterize the switching mechanism for the alphaC helix and the activation-loop in detail. Finally, we test the performance of a Markov model and its ability to account for the structural kinetics in the context of Src conformational changes. Taken together, these results provide a broad framework for understanding the main features of the conformational transition taking place upon Src activation.

  3. Conformation, orientation and interaction in molecular monolayers

    International Nuclear Information System (INIS)

    Superfine, R.; Huang, J.Y.; Shen, Y.R.

    1989-01-01

    Knowledge of the conformation and ordering of molecular monolayers is essential for a detailed understanding of a wide variety of surface and interfacial phenomena. Over the past several years, surface second harmonic generation (SHG) has proven to be a valuable and versatile probe of monolayer systems. Our group has recently extended the technique to infrared-visible sum frequency generation (SFG) which has unique capabilities for surface vibrational spectroscopy. Like second harmonic generation, SFG is highly surface specific with submonolayer sensitivity at all interfaces accessible by light. The orientation of individual groups within an adsorbate molecule can be deduced by a polarization analysis of the SFG signal from the vibrational modes of the groups. The authors have used SHG and SFG to study orientations and conformations of surfactant and liquid crystal (LC) monolayers and their interaction on a substrate. The interfacial properties of LC are of great interest to many researchers for both basic science understanding and practical application to LC devices. It is well known that the bulk alignment of a liquid crystal in a cell is strongly affected by the surface treatment of the cell walls. The reason behind it is not yet clear. The theoretical background and experimental arrangement of SHG and SFG have been described elsewhere. In the setup, a 30 psec. Nd:YAG mode-locked laser system together with nonlinear accessories generates a visible beam at .532μm and an infrared beam tunable about 3.4μm. Both beams are focused to a common spot of 300μm dia. The typical signal off the surface from a compact ordered alkyl chain monolayer is ∼500 photons per pulse, easily detected with a photomultiplier tube

  4. Dual-cyclical nucleic acid strand-displacement polymerization based signal amplification system for highly sensitive determination of p53 gene.

    Science.gov (United States)

    Xu, Jianguo; Wu, Zai-Sheng; Li, Hongling; Wang, Zhenmeng; Le, Jingqing; Zheng, Tingting; Jia, Lee

    2016-12-15

    In the present study, we proposed a novel dual-cyclical nucleic acid strand-displacement polymerization (dual-CNDP) based signal amplification system for highly sensitive determination of tumor suppressor genes. The system primarily consisted of a signaling hairpin probe (SHP), a label-free hairpin probe (LHP) and an initiating primer (IP). The presence of target DNA was able to induce one CNDP through continuous process of ligation, polymerization and nicking, leading to extensively accumulation of two nicked triggers (NT1 and NT2). Intriguingly, the NT1 could directly hybridize SHP, while the NT2 could act as the target analog to induce another CNDP. The resulting dual-CNDP contributed the striking signal amplification, and only a very weak blank noise existed since the ligation template of target was not involved. In this case, the target could be detected in a wide linear range (5 orders of magnitude), and a low detection limit (78 fM) was obtained, which is superior to most of the existing fluorescent methods. Moreover, the dual-CNDP sensing system provided a high selectivity towards target DNA against mismatched target and was successfully applied to analysis of target gene extracted from cancer cells or in human serum-contained samples, indicating its great potential for practical applications. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Real-time determination of the signal-to-noise ratio of partly coherent seismic time series

    DEFF Research Database (Denmark)

    Kjeldsen, Peter Møller

    1994-01-01

    it is of great practical interest to be able to monitor the S/N while the traces are recorded an approach for fast real-time determination of the S/N of seismic time series is proposed. The described method is based on an iterative procedure utilizing the trace-to-trace coherence, but unlike procedures known so...... far it uses calculated initial guesses and stop criterions. This significantly reduces the computational burden of the procedure so that real-time capabilities are obtained...

  6. Spin-4 extended conformal algebras

    International Nuclear Information System (INIS)

    Kakas, A.C.

    1988-01-01

    We construct spin-4 extended conformal algebras using the second hamiltonian structure of the KdV hierarchy. In the presence of a U(1) current a family of spin-4 algebras exists but the additional requirement that the spin-1 and spin-4 currents commute fixes the algebra uniquely. (orig.)

  7. Conformal symmetry and holographic cosmology

    NARCIS (Netherlands)

    Bzowski, A.W.

    2013-01-01

    This thesis presents a novel approach to cosmology using gauge/gravity duality. Analysis of the implications of conformal invariance in field theories leads to quantitative cosmological predictions which are in agreement with current data. Furthermore, holographic cosmology extends the theory of

  8. Checking behavioral conformance of artifacts

    NARCIS (Netherlands)

    Fahland, D.; Leoni, de M.; Dongen, van B.F.; Aalst, van der W.M.P.

    2011-01-01

    The usefulness of process models (e.g., for analysis, improvement, or execution) strongly depends on their ability to describe reality. Conformance checking is a technique to validate how good a given process model describes recorded executions of the actual process. Recently, artifacts have been

  9. Conformation analysis of oligomeric flavanoids

    Science.gov (United States)

    Jan P. Steynberg; E. Vincent Brandt; Daneel Ferreira; Carin A. Helfer; Wayne L. Mattice; Dominika Gornik; Richard W. Hemingway

    1995-01-01

    The profisetinidins are the most important polyflavanoids of commerce, making up the major constituents of wattle and quebracho tannins. Within the dimeric profisetinidins, substantial complexity exists because of stereo-, regio, rotational and conformational isomers. Definition of the stereochemistry of the upper and lower flavan units, the location of the...

  10. Conformational analysis of oligomeric flavanoids

    Science.gov (United States)

    Jan P. Steynberg; E. Vincent Brandt; Daneel Ferreira; Carin A. Helfer; Wayne L. Mattice; Dominika Gornik; Richard W. Hemingway

    1995-01-01

    The profisetinidins are the most important polyflavanoids of commerce, making up the major constituents of wattle and quebracho tannins. Even within the dimeric profisetinidins, substantial complexity exists because of stereo-, regio-, rotational and conformational isomers. Definition of the stereochemistry of the upper and lower flavan units, the location of the...

  11. Inversion theory and conformal mapping

    CERN Document Server

    Blair, David E

    2000-01-01

    It is rarely taught in an undergraduate or even graduate curriculum that the only conformal maps in Euclidean space of dimension greater than two are those generated by similarities and inversions in spheres. This is in stark contrast to the wealth of conformal maps in the plane. The principal aim of this text is to give a treatment of this paucity of conformal maps in higher dimensions. The exposition includes both an analytic proof in general dimension and a differential-geometric proof in dimension three. For completeness, enough complex analysis is developed to prove the abundance of conformal maps in the plane. In addition, the book develops inversion theory as a subject, along with the auxiliary theme of circle-preserving maps. A particular feature is the inclusion of a paper by Carath�odory with the remarkable result that any circle-preserving transformation is necessarily a M�bius transformation, not even the continuity of the transformation is assumed. The text is at the level of advanced undergr...

  12. Supertwistor connection and conformal supergravity

    International Nuclear Information System (INIS)

    Merkulov, S.A.

    1985-01-01

    Supersymmetry expansion of the geometry of local twistors is suggested. Definition of the space of local supertwistors is given and its differential geometry is formulated. Variational principles are discussed, and it is shown that corresponding Euler-Lagrange equations also coincide and result in superzero equations of N=1 conformal supergravitation, which generalize Bach equations

  13. Exceptional and Spinorial Conformal Windows

    DEFF Research Database (Denmark)

    Mojaza, Matin; Pica, Claudio; Ryttov, Thomas

    2012-01-01

    We study the conformal window of gauge theories containing fermionic matter fields, where the gauge group is any of the exceptional groups with the fermions transforming according to the fundamental and adjoint representations and the orthogonal groups where the fermions transform according...

  14. Structural alphabets derived from attractors in conformational space

    Directory of Open Access Journals (Sweden)

    Kleinjung Jens

    2010-02-01

    Full Text Available Abstract Background The hierarchical and partially redundant nature of protein structures justifies the definition of frequently occurring conformations of short fragments as 'states'. Collections of selected representatives for these states define Structural Alphabets, describing the most typical local conformations within protein structures. These alphabets form a bridge between the string-oriented methods of sequence analysis and the coordinate-oriented methods of protein structure analysis. Results A Structural Alphabet has been derived by clustering all four-residue fragments of a high-resolution subset of the protein data bank and extracting the high-density states as representative conformational states. Each fragment is uniquely defined by a set of three independent angles corresponding to its degrees of freedom, capturing in simple and intuitive terms the properties of the conformational space. The fragments of the Structural Alphabet are equivalent to the conformational attractors and therefore yield a most informative encoding of proteins. Proteins can be reconstructed within the experimental uncertainty in structure determination and ensembles of structures can be encoded with accuracy and robustness. Conclusions The density-based Structural Alphabet provides a novel tool to describe local conformations and it is specifically suitable for application in studies of protein dynamics.

  15. Relational motivation for conformal operator ordering in quantum cosmology

    International Nuclear Information System (INIS)

    Anderson, Edward

    2010-01-01

    Operator ordering in quantum cosmology is a major as-yet unsettled ambiguity with not only formal but also physical consequences. We determine the Lagrangian origin of the conformal invariance that underlies the conformal operator-ordering choice in quantum cosmology. This arises particularly naturally and simply from relationalist product-type actions (such as the Jacobi action for mechanics or Baierlein-Sharp-Wheeler-type actions for general relativity), for which all that is required is for the kinetic and potential factors to rescale in compensation to each other. These actions themselves mathematically sharply implement philosophical principles relevant to whole-universe modelling, so that the motivation for conformal operator ordering in quantum cosmology is thereby substantially strengthened. Relationalist product-type actions also give emergent times which amount to recovering Newtonian, proper and cosmic time in various contexts. The conformal scaling of these actions directly tells us how emergent time scales; if one follows suit with the Newtonian time or the lapse in the more commonly used difference-type Euler-Lagrange or Arnowitt-Deser-Misner-type actions, one sees how these too obey a more complicated conformal invariance. Moreover, our discovery of the conformal scaling of the emergent time permits relating how this simplifies equations of motion with how affine parametrization simplifies geodesics.

  16. Nonperturbative results for two-index conformal windows

    Energy Technology Data Exchange (ETDEWEB)

    Bergner, Georg [Albert Einstein Center for Fundamental Physics,Institute for Theoretical Physics, University of Bern,Sidlerstrasse 5, CH-3012 Bern (Switzerland); Ryttov, Thomas A.; Sannino, Francesco [CP-Origins and the Danish IAS, University of Southern Denmark,5230 Odense M (Denmark)

    2015-12-10

    Via large and small N{sub c} relations we derive nonperturbative results about the conformal window of two-index theories. Using Schwinger-Dyson methods as well as four-loops results we estimate subleading corrections and show that naive large number of colors extrapolations are unreliable when N{sub c} is less than about six. Nevertheless useful nonperturbative inequalities for the size of the conformal windows, for any number of colors, can be derived. By further observing that the adjoint conformal window is independent of the number of colors we argue, among other things, that: the large N{sub c} two-index conformal window is twice the conformal window of the adjoint representation (which can be determined at small N{sub c}) expressed in terms of Dirac fermions; lattice results for adjoint matter can be used to provide independent information on the conformal dynamics of two-index theories such as SU(N{sub c}) with two and four symmetric Dirac flavors.

  17. Determining

    Directory of Open Access Journals (Sweden)

    Bahram Andarzian

    2015-06-01

    Full Text Available Wheat production in the south of Khuzestan, Iran is constrained by heat stress for late sowing dates. For optimization of yield, sowing at the appropriate time to fit the cultivar maturity length and growing season is critical. Crop models could be used to determine optimum sowing window for a locality. The objectives of this study were to evaluate the Cropping System Model (CSM-CERES-Wheat for its ability to simulate growth, development, grain yield of wheat in the tropical regions of Iran, and to study the impact of different sowing dates on wheat performance. The genetic coefficients of cultivar Chamran were calibrated for the CSM-CERES-Wheat model and crop model performance was evaluated with experimental data. Wheat cultivar Chamran was sown on different dates, ranging from 5 November to 9 January during 5 years of field experiments that were conducted in the Khuzestan province, Iran, under full and deficit irrigation conditions. The model was run for 8 sowing dates starting on 25 October and repeated every 10 days until 5 January using long-term historical weather data from the Ahvaz, Behbehan, Dezful and Izeh locations. The seasonal analysis program of DSSAT was used to determine the optimum sowing window for different locations as well. Evaluation with the experimental data showed that performance of the model was reasonable as indicated by fairly accurate simulation of crop phenology, biomass accumulation and grain yield against measured data. The normalized RMSE were 3%, 2%, 11.8%, and 3.4% for anthesis date, maturity date, grain yield and biomass, respectively. Optimum sowing window was different among locations. It was opened and closed on 5 November and 5 December for Ahvaz; 5 November and 15 December for Behbehan and Dezful;and 1 November and 15 December for Izeh, respectively. CERES-Wheat model could be used as a tool to evaluate the effect of sowing date on wheat performance in Khuzestan conditions. Further model evaluations

  18. 75 FR 20591 - AES Sparrows Point LNG, LLC and Mid-Atlantic Express, LLC; Notice of Final General Conformity...

    Science.gov (United States)

    2010-04-20

    ...] AES Sparrows Point LNG, LLC and Mid-Atlantic Express, LLC; Notice of Final General Conformity... revised draft Final General Conformity Determination (GCD) for Pennsylvania to assess the potential air... the above-referenced dockets. In accordance with the General Conformity Regulations under the Code of...

  19. Polycyclic aromatic hydrocarbons and dibutyl phthalate disrupt dorsal-ventral axis determination via the Wnt/{beta}-catenin signaling pathway in zebrafish embryos

    Energy Technology Data Exchange (ETDEWEB)

    Fairbairn, Elise A., E-mail: efairbairn@ucdavis.edu [University of California Davis, Bodega Marine Laboratory, P.O. Box 247, Bodega Bay, CA 94923 (United States); Bonthius, Jessica, E-mail: jessica.bonthius@gmail.com [University of California Davis, Bodega Marine Laboratory, P.O. Box 247, Bodega Bay, CA 94923 (United States); Cherr, Gary N., E-mail: gncherr@ucdavis.edu [University of California Davis, Bodega Marine Laboratory, P.O. Box 247, Bodega Bay, CA 94923 (United States); Department of Environmental Toxicology, University of California Davis, Davis, CA 95616 (United States); Department of Nutrition, University of California Davis, Davis, CA 95616 (United States)

    2012-11-15

    The canonical Wnt/{beta}-catenin signaling pathway is critical during early teleost development for establishing the dorsal-ventral axis. Within this pathway, GSK-3{beta}, a key regulatory kinase in the Wnt pathway, regulates {beta}-catenin degradation and thus the ability of {beta}-catenin to enter nuclei, where it can activate expression of genes that have been linked to the specification of the dorsal-ventral axis. In this study, we describe the morphological abnormalities that resulted in zebrafish embryos when axis determination was disrupted by environmental contaminants. These abnormalities were linked to abnormal nuclear accumulation of {beta}-catenin. Furthermore, we demonstrated that the developmental abnormalities and altered nuclear {beta}-catenin accumulation occurred when embryos were exposed to commercial GSK-3{beta} inhibitors. Zebrafish embryos were exposed to commercially available GSK-3 inhibitors (GSK-3 Inhibitor IX and 1-azakenpaullone), or common environmental contaminants (dibutyl phthalate or the polycyclic aromatic hydrocarbons phenanthrene and fluorene) from the 2 to 8-cell stage through the mid-blastula transition (MBT). These embryos displayed morphological abnormalities at 12.5 h post-fertilization (hpf) that were comparable to embryos exposed to lithium chloride (LiCl) (300 mM LiCl for 10 min, prior to the MBT), a classic disruptor of embryonic axis determination. Whole-mount immunolabeling and laser scanning confocal microscopy were used to localize {beta}-catenin. The commercial GSK-3 Inhibitors as well as LiCl, dibutyl phthalate, fluorene and phenanthrene all induced an increase in the levels of nuclear {beta}-catenin throughout the embryo, indicating that the morphological abnormalities were a result of disruption of Wnt/{beta}-catenin signaling during dorsal-ventral axis specification. The ability of environmental chemicals to directly or indirectly target GSK-3{beta} was assessed. Using Western blot analysis, the ability of these

  20. Logarithmic conformal field theory: beyond an introduction

    International Nuclear Information System (INIS)

    Creutzig, Thomas; Ridout, David

    2013-01-01

    studied here by first determining its irreducible spectrum, which turns out to be continuous, as well as a selection of natural reducible, but indecomposable, modules. This is followed by a detailed description of how to obtain character formulae for each irreducible, a derivation of the action of the modular group on the characters, and an application of the Verlinde formula to compute the Grothendieck fusion rules. In each case, the (genuine) fusion rules are known, so comparisons can be made and favourable conclusions drawn. In addition, each example admits an infinite set of simple currents, hence extended symmetry algebras may be constructed and a series of bulk modular invariants computed. The spectrum of such an extended theory is typically discrete and this is how the triplet model W(1,2) arises, for example. Moreover, simple current technology admits a derivation of the extended algebra fusion rules from those of its continuous parent theory. Finally, each example is concluded by a brief description of the computation of some bulk correlators, a discussion of the structure of the bulk state space, and remarks concerning more advanced developments and generalizations. The final part gives a very short account of the theory of staggered modules, the (simplest class of) representations that are responsible for the logarithmic singularities that distinguish logarithmic theories from their rational cousins. These modules are discussed in a generality suitable to encompass all the examples met in this review and some of the very basic structure theory is proven. Then, the important quantities known as logarithmic couplings are reviewed for Virasoro staggered modules and their role as fundamentally important parameters, akin to the three-point constants of rational conformal field theory, is discussed. An appendix is also provided in order to introduce some of the necessary, but perhaps unfamiliar, language of homological algebra. (review)

  1. Electrodynamics with a Future Conformal Horizon

    International Nuclear Information System (INIS)

    Ibison, Michael

    2010-01-01

    We investigate the impact of singularities occurring at future times in the Friedmann equations expressed in conformal coordinates to determine the consequences of extending the time coordinate through the singularity for the physics of matter and radiation occupying just one side. Mostly this involves investigation of the relationship between the metric with line element ds 2 a 2 (t)(dt 2 -dx 2 ) and time reversal symmetry within electrodynamics. It turns out compatibility between these two is possible only if there is a singular physical event at the time of the singularity or if the topology is not trivial. In both cases the singularity takes on the appearance of a time-like mirror. We are able to demonstrate a relationship between the broken time symmetry in electrodynamics characterized by retarded radiation and radiation reaction and the absolute conformal time relative to the time of the singularity, i.e. between the Electromagnetic and Cosmological arrows of time. It is determined that the Wheeler-Feynman reasoning but with the future absorber replaced by the Cosmological mirror leads to a conflict with observation unless matter is strongly bound electromagnetically to the environment.

  2. An Lmx1b-miR135a2 regulatory circuit modulates Wnt1/Wnt signaling and determines the size of the midbrain dopaminergic progenitor pool.

    Directory of Open Access Journals (Sweden)

    Angela Anderegg

    Full Text Available MicroRNAs regulate gene expression in diverse physiological scenarios. Their role in the control of morphogen related signaling pathways has been less studied, particularly in the context of embryonic Central Nervous System (CNS development. Here, we uncover a role for microRNAs in limiting the spatiotemporal range of morphogen expression and function. Wnt1 is a key morphogen in the embryonic midbrain, and directs proliferation, survival, patterning and neurogenesis. We reveal an autoregulatory negative feedback loop between the transcription factor Lmx1b and a newly characterized microRNA, miR135a2, which modulates the extent of Wnt1/Wnt signaling and the size of the dopamine progenitor domain. Conditional gain of function studies reveal that Lmx1b promotes Wnt1/Wnt signaling, and thereby increases midbrain size and dopamine progenitor allocation. Conditional removal of Lmx1b has the opposite effect, in that expansion of the dopamine progenitor domain is severely compromised. Next, we provide evidence that microRNAs are involved in restricting dopamine progenitor allocation. Conditional loss of Dicer1 in embryonic stem cells (ESCs results in expanded Lmx1a/b+ progenitors. In contrast, forced elevation of miR135a2 during an early window in vivo phenocopies the Lmx1b conditional knockout. When En1::Cre, but not Shh::Cre or Nes::Cre, is used for recombination, the expansion of Lmx1a/b+ progenitors is selectively reduced. Bioinformatics and luciferase assay data suggests that miR135a2 targets Lmx1b and many genes in the Wnt signaling pathway, including Ccnd1, Gsk3b, and Tcf7l2. Consistent with this, we demonstrate that this mutant displays reductions in the size of the Lmx1b/Wnt1 domain and range of canonical Wnt signaling. We posit that microRNA modulation of the Lmx1b/Wnt axis in the early midbrain/isthmus could determine midbrain size and allocation of dopamine progenitors. Since canonical Wnt activity has recently been recognized as a key

  3. Orientation and conformation of a lipase at an interface studied by molecular dynamics simulations

    DEFF Research Database (Denmark)

    Jensen, Morten Østergaard; Jensen, T.R.; Kjær, Kristian

    2002-01-01

    Electron density profiles calculated from molecular dynamics trajectories are used to deduce the orientation and conformation of Thermomyces lanuginosa lipase and a mutant adsorbed at an air-water interface. It is demonstrated that the profiles display distinct fine structures, which uniquely...... characterize enzyme orientation and conformation. The density profiles are, on the nanosecond timescale, determined by the average enzyme conformation. We outline a Computational scheme that from a single molecular dynamics trajectory allows for extraction of electron density profiles referring to different...

  4. Conformal invariance at a deconfinement phase transition in (2+1) dimensions

    International Nuclear Information System (INIS)

    Christensen, J.; Damgaard, P.H.

    1990-08-01

    The conformal dimension of the Polyakov line at the deconfinement phase transition of (2+1)-dimensional SU(2) lattice gauge theory is determined numerically using two-dimensional finite size conformal field theory. Excellent agreement with two-dimensional Ising model values is found for both the renormalized coupling on a spatially toroidal geometry and the conformal dimensions on a finite-width strip geometry. (orig.)

  5. Triple-Frequency Code-Phase Combination Determination: A Comparison with the Hatch-Melbourne-Wübbena Combination Using BDS Signals

    Directory of Open Access Journals (Sweden)

    Chenlong Deng

    2018-02-01

    Full Text Available Considering the influence of the ionosphere, troposphere, and other systematic errors on double-differenced ambiguity resolution (AR, we present an optimal triple-frequency code-phase combination determination method driven by both the model and the real data. The new method makes full use of triple-frequency code measurements (especially the low-noise of the code on the B3 signal to minimize the total noise level and achieve the largest AR success rate (model-driven under different ionosphere residual situations (data-driven, thus speeding up the AR by directly rounding. With the triple-frequency Beidou Navigation Satellite System (BDS data collected at five stations from a continuously-operating reference station network in Guangdong Province of China, different testing scenarios are defined (a medium baseline, whose distance is between 20 km and 50 km; a medium-long baseline, whose distance is between 50 km and 100 km; and a long baseline, whose distance is larger than 100 km. The efficiency of the optimal code-phase combination on the AR success rate was compared with that of the geometry-free and ionosphere-free (GIF combination and the Hatch-Melbourne-Wübbena (HMW combination. Results show that the optimal combinations can always achieve better results than the HMW combination with B2 and B3 signals, especially when the satellite elevation angle is larger than 45°. For the wide-lane AR which aims to obtain decimeter-level kinematic positioning service, the standard deviation (STD of ambiguity residuals for the suboptimal combination are only about 0.2 cycles, and the AR success rate by directly rounding can be up to 99%. Compared with the HMW combinations using B1 and B2 signals and using B1 and B3 signals, the suboptimal combination achieves the best results in all baselines, with an overall improvement of about 40% and 20%, respectively. Additionally, the STD difference between the optimal and the GIF code-phase combinations decreases

  6. Conformational transitions and interactions underlying the function of membrane embedded receptor protein kinases.

    Science.gov (United States)

    Bocharov, Eduard V; Sharonov, Georgy V; Bocharova, Olga V; Pavlov, Konstantin V

    2017-09-01

    Among membrane receptors, the single-span receptor protein kinases occupy a broad but specific functional niche determined by distinctive features of the underlying transmembrane signaling mechanisms that are briefly overviewed on the basis of some of the most representative examples, followed by a more detailed discussion of several hierarchical levels of organization and interactions involved. All these levels, including single-molecule interactions (e.g., dimerization, liganding, chemical modifications), local processes (e.g. lipid membrane perturbations, cytoskeletal interactions), and larger scale phenomena (e.g., effects of membrane surface shape or electrochemical potential gradients) appear to be closely integrated to achieve the observed diversity of the receptor functioning. Different species of receptor protein kinases meet their specific functional demands through different structural features defining their responses to stimulation, but certain common patterns exist. Signaling by receptor protein kinases is typically associated with the receptor dimerization and clustering, ligand-induced rearrangements of receptor domains through allosteric conformational transitions with involvement of lipids, release of the sequestered lipids, restriction of receptor diffusion, cytoskeleton and membrane shape remodeling. Understanding of complexity and continuity of the signaling processes can help identifying currently neglected opportunities for influencing the receptor signaling with potential therapeutic implications. This article is part of a Special Issue entitled: Interactions between membrane receptors in cellular membranes edited by Kalina Hristova. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Conformers, infrared spectrum, UV-induced photochemistry, and near-IR-induced generation of two rare conformers of matrix-isolated phenylglycine

    Science.gov (United States)

    Borba, Ana; Gómez-Zavaglia, Andrea; Fausto, Rui

    2014-10-01

    The conformational space of α-phenylglycine (PG) have been investigated theoretically at both the DFT/B3LYP/6-311++G(d,p) and MP2/6-311++G(d,p) levels of approximation. Seventeen different minima were found on the investigated potential energy surfaces, which are characterized by different dominant intramolecular interactions: type I conformers are stabilized by hydrogen bonds of the type N-H...O=C, type II by a strong O-H...N hydrogen bond, type III by weak N-H...O-H hydrogen bonds, and type IV by a C=O...H-C contact. The calculations indicate also that entropic effects are relevant in determining the equilibrium populations of the conformers of PG in the gas phase, in particular in the case of conformers of type II, where the strong intramolecular O-H...N hydrogen bond considerably diminishes entropy by reducing the conformational mobility of the molecule. In consonance with the relative energies of the conformers and barriers for conformational interconversion, only 3 conformers of PG were observed for the compound isolated in cryogenic Ar, Xe, and N2 matrices: the conformational ground state (ICa), and forms ICc and IITa. All other significantly populated conformers existing in the gas phase prior to deposition convert either to conformer ICa or to conformer ICc during matrix deposition. The experimental observation of ICc had never been achieved hitherto. Narrowband near-IR irradiation of the first overtone of νOH vibrational mode of ICa and ICc in nitrogen matrices (at 6910 and 6930 cm-1, respectively) led to selective generation of two additional conformers of high-energy, ITc and ITa, respectively, which were also observed experimentally for the first time. In addition, these experiments also provided the key information for the detailed vibrational characterization of the 3 conformers initially present in the matrices. On the other hand, UV irradiation (λ = 255 nm) of PG isolated in a xenon matrix revealed that PG undergoes facile photofragmentation

  8. Conformers, infrared spectrum, UV-induced photochemistry, and near-IR-induced generation of two rare conformers of matrix-isolated phenylglycine

    International Nuclear Information System (INIS)

    Borba, Ana; Fausto, Rui; Gómez-Zavaglia, Andrea

    2014-01-01

    The conformational space of α-phenylglycine (PG) have been investigated theoretically at both the DFT/B3LYP/6-311++G(d,p) and MP2/6-311++G(d,p) levels of approximation. Seventeen different minima were found on the investigated potential energy surfaces, which are characterized by different dominant intramolecular interactions: type I conformers are stabilized by hydrogen bonds of the type N–H···O=C, type II by a strong O–H···N hydrogen bond, type III by weak N–H···O–H hydrogen bonds, and type IV by a C=O···H–C contact. The calculations indicate also that entropic effects are relevant in determining the equilibrium populations of the conformers of PG in the gas phase, in particular in the case of conformers of type II, where the strong intramolecular O–H···N hydrogen bond considerably diminishes entropy by reducing the conformational mobility of the molecule. In consonance with the relative energies of the conformers and barriers for conformational interconversion, only 3 conformers of PG were observed for the compound isolated in cryogenic Ar, Xe, and N 2 matrices: the conformational ground state (ICa), and forms ICc and IITa. All other significantly populated conformers existing in the gas phase prior to deposition convert either to conformer ICa or to conformer ICc during matrix deposition. The experimental observation of ICc had never been achieved hitherto. Narrowband near-IR irradiation of the first overtone of νOH vibrational mode of ICa and ICc in nitrogen matrices (at 6910 and 6930 cm −1 , respectively) led to selective generation of two additional conformers of high-energy, ITc and ITa, respectively, which were also observed experimentally for the first time. In addition, these experiments also provided the key information for the detailed vibrational characterization of the 3 conformers initially present in the matrices. On the other hand, UV irradiation (λ = 255 nm) of PG isolated in a xenon matrix revealed that PG

  9. Conformal and Nearly Conformal Theories at Large N

    Science.gov (United States)

    Tarnoplskiy, Grigory M.

    In this thesis we present new results in conformal and nearly conformal field theories in various dimensions. In chapter two, we study different properties of the conformal Quantum Electrodynamics (QED) in continuous dimension d. At first we study conformal QED using large Nf methods, where Nf is the number of massless fermions. We compute its sphere free energy as a function of d, ignoring the terms of order 1/Nf and higher. For finite Nf we use the epsilon-expansion. Next we use a large Nf diagrammatic approach to calculate the leading corrections to CT, the coefficient of the two-point function of the stress-energy tensor, and CJ, the coefficient of the two-point function of the global symmetry current. We present explicit formulae as a function of d and check them versus the expectations in 2 and 4 - epsilon dimensions. In chapter three, we discuss vacuum stability in 1 + 1 dimensional conformal field theories with external background fields. We show that the vacuum decay rate is given by a non-local two-form. This two-form is a boundary term that must be added to the effective in/out Lagrangian. The two-form is expressed in terms of a Riemann-Hilbert decomposition for background gauge fields, and is given by its novel "functional'' version in the gravitational case. In chapter four, we explore Tensor models. Such models possess the large N limit dominated by the melon diagrams. The quantum mechanics of a real anti-commuting rank-3 tensor has a large N limit similar to the Sachdev-Ye-Kitaev (SYK) model. We also discuss the quantum mechanics of a complex 3-index anti-commuting tensor and argue that it is equivalent in the large N limit to a version of SYK model with complex fermions. Finally, we discuss models of a commuting tensor in dimension d. We study the spectrum of the large N quantum field theory of bosonic rank-3 tensors using the Schwinger-Dyson equations. We compare some of these results with the 4 - epsilon expansion, finding perfect agreement. We

  10. Conformal invariance in the quantum field theory

    International Nuclear Information System (INIS)

    Kurak, V.

    1975-09-01

    Basic features concerning the present knowledge of conformal symmetry are illustrated in a simple model. Composite field dimensions of this model are computed and related to the conformal group. (author) [pt

  11. The Conformational Behaviour of Glucosamine

    Science.gov (United States)

    Peña, Isabel; Kolesniková, Lucie; Cabezas, Carlos; Bermúdez, Celina; Berdakin, Matías; Simao, Alcides; Alonso, José L.

    2014-06-01

    A laser ablation method has been successfully used to vaporize the bioactive amino monosaccharide D-glucosamine. Three cyclic α-4C1 pyranose forms have been identified using a combination of CP-FTMW and LA-MB-FTMW spectroscopy. Stereoelectronic hyperconjugative factors, like those associated with anomeric or gauche effects, as well as the cooperative OH\\cdotsO, OH\\cdotsN and NH\\cdotsO chains, extended along the entire molecule, are the main factors driving the conformational behavior. All observed conformers exhibit a counter-clockwise arrangement (cc) of the network of intramolecular hydrogen bonds. The results are compared with those recently obtained for D-glucose. J. L. Alonso, M. A. Lozoya, I. Peña, J. C. López, C. Cabezas, S. Mata, S. Blanco, Chem. Sci. 2014, 5, 515.

  12. Conformal invariance from nonconformal gravity

    International Nuclear Information System (INIS)

    Meissner, Krzysztof A.; Nicolai, Hermann

    2009-01-01

    We discuss the conditions under which classically conformally invariant models in four dimensions can arise out of nonconformal (Einstein) gravity. As an 'existence proof' that this is indeed possible we show how to derive N=4 super Yang-Mills theory with any compact gauge group G from nonconformal gauged N=4 supergravity as a special flat space limit. We stress the role that the anticipated UV finiteness of the (so far unknown) underlying theory of quantum gravity would have to play in such a scheme, as well as the fact that the masses of elementary particles would have to arise via quantum gravitational effects which mimic the conformal anomalies of standard (flat space) UV divergent quantum field theory.

  13. Conformal methods in general relativity

    CERN Document Server

    Valiente Kroon, Juan A

    2016-01-01

    This book offers a systematic exposition of conformal methods and how they can be used to study the global properties of solutions to the equations of Einstein's theory of gravity. It shows that combining these ideas with differential geometry can elucidate the existence and stability of the basic solutions of the theory. Introducing the differential geometric, spinorial and PDE background required to gain a deep understanding of conformal methods, this text provides an accessible account of key results in mathematical relativity over the last thirty years, including the stability of de Sitter and Minkowski spacetimes. For graduate students and researchers, this self-contained account includes useful visual models to help the reader grasp abstract concepts and a list of further reading, making this the perfect reference companion on the topic.

  14. Gel dosimetry for conformal radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Gambarini, G [Department of Physics of the University and INFN, Milan (Italy)

    2005-07-01

    With the continuum development of conformal radio therapies, aimed at delivering high dose to tumor tissue and low dose to the healthy tissue around, the necessities has appeared of suitable improvement of dosimetry techniques giving the possibility of obtaining dose images to be compared with diagnostic images. Also if wide software has been developed for calculating dose distributions in the fields of various radiotherapy units, experimental verifications are necessary, in particular in the case of complex geometries in conformal radiotherapy. Gel dosimetry is a promising method for imaging the absorbed dose in tissue-equivalent phantoms, with the possibility of 3D reconstruction of the spatial dose distribution, with milli metric resolution. Optical imaging of gel dosimeters, based on visible light absorbance analysis, has shown to be a reliable technique for achieving dose distributions. (Author)

  15. Conformal FDTD modeling wake fields

    Energy Technology Data Exchange (ETDEWEB)

    Jurgens, T.; Harfoush, F.

    1991-05-01

    Many computer codes have been written to model wake fields. Here we describe the use of the Conformal Finite Difference Time Domain (CFDTD) method to model the wake fields generated by a rigid beam traveling through various accelerating structures. The non- cylindrical symmetry of some of the problems considered here requires the use of a three dimensional code. In traditional FDTD codes, curved surfaces are approximated by rectangular steps. The errors introduced in wake field calculations by such an approximation can be reduced by increasing the mesh size, therefore increasing the cost of computing. Another approach, validated here, deforms Ampere and Faraday contours near a media interface so as to conform to the interface. These improvements of the FDTD method result in better accuracy of the fields at asymptotically no computational cost. This method is also capable of modeling thin wires as found in beam profile monitors, and slots and cracks as found in resistive wall motions. 4 refs., 5 figs.

  16. Conformal manifolds: ODEs from OPEs

    Science.gov (United States)

    Behan, Connor

    2018-03-01

    The existence of an exactly marginal deformation in a conformal field theory is very special, but it is not well understood how this is reflected in the allowed dimensions and OPE coefficients of local operators. To shed light on this question, we compute perturbative corrections to several observables in an abstract CFT, starting with the beta function. This yields a sum rule that the theory must obey in order to be part of a conformal manifold. The set of constraints relating CFT data at different values of the coupling can in principle be written as a dynamical system that allows one to flow arbitrarily far. We begin the analysis of it by finding a simple form for the differential equations when the spacetime and theory space are both one-dimensional. A useful feature we can immediately observe is that our system makes it very difficult for level crossing to occur.

  17. Conformal field theories and critical phenomena

    International Nuclear Information System (INIS)

    Xu, Bowei

    1993-01-01

    In this article we present a brief review of the conformal symmetry and the two dimensional conformal quantum field theories. As concrete applications of the conformal theories to the critical phenomena in statistical systems, we calculate the value of central charge and the anomalous scale dimensions of the Z 2 symmetric quantum chain with boundary condition. The results are compatible with the prediction of the conformal field theories

  18. Conformal group actions and Segal's cosmology

    International Nuclear Information System (INIS)

    Werth, J.-E.

    1984-01-01

    A mathematical description of Segal's cosmological model in the framework of conformal group actions is presented. The relation between conformal and causal group actions on time-orientable Lorentzian manifolds is analysed and several examples are discussed. A criterion for the conformality of a map between Lorentzian manifolds is given. The results are applied to Segal's 'conformal compactification' of Minkowski space. Furthermore, the 'unitary formulation' of Segal's cosmology is regarded. (Author) [pt

  19. Generative Models of Conformational Dynamics

    OpenAIRE

    Langmead, Christopher James

    2014-01-01

    Atomistic simulations of the conformational dynamics of proteins can be performed using either Molecular Dynamics or Monte Carlo procedures. The ensembles of three-dimensional structures produced during simulation can be analyzed in a number of ways to elucidate the thermodynamic and kinetic properties of the system. The goal of this chapter is to review both traditional and emerging methods for learning generative models from atomistic simulation data. Here, the term ‘generative’ refers to a...

  20. Holographic multiverse and conformal invariance

    Energy Technology Data Exchange (ETDEWEB)

    Garriga, Jaume [Departament de Física Fonamental i Institut de Ciències del Cosmos, Universitat de Barcelona, Martí i Franquès 1, 08193 Barcelona (Spain); Vilenkin, Alexander, E-mail: jaume.garriga@ub.edu, E-mail: vilenkin@cosmos.phy.tufts.edu [Institute of Cosmology, Department of Physics and Astronomy, Tufts University, 212 College Ave., Medford, MA 02155 (United States)

    2009-11-01

    We consider a holographic description of the inflationary multiverse, according to which the wave function of the universe is interpreted as the generating functional for a lower dimensional Euclidean theory. We analyze a simple model where transitions between inflationary vacua occur through bubble nucleation, and the inflating part of spacetime consists of de Sitter regions separated by thin bubble walls. In this model, we present some evidence that the dual theory is conformally invariant in the UV.

  1. Holographic multiverse and conformal invariance

    International Nuclear Information System (INIS)

    Garriga, Jaume; Vilenkin, Alexander

    2009-01-01

    We consider a holographic description of the inflationary multiverse, according to which the wave function of the universe is interpreted as the generating functional for a lower dimensional Euclidean theory. We analyze a simple model where transitions between inflationary vacua occur through bubble nucleation, and the inflating part of spacetime consists of de Sitter regions separated by thin bubble walls. In this model, we present some evidence that the dual theory is conformally invariant in the UV

  2. Integrability of conformal fishnet theory

    Science.gov (United States)

    Gromov, Nikolay; Kazakov, Vladimir; Korchemsky, Gregory; Negro, Stefano; Sizov, Grigory

    2018-01-01

    We study integrability of fishnet-type Feynman graphs arising in planar four-dimensional bi-scalar chiral theory recently proposed in arXiv:1512.06704 as a special double scaling limit of gamma-deformed N = 4 SYM theory. We show that the transfer matrix "building" the fishnet graphs emerges from the R-matrix of non-compact conformal SU(2 , 2) Heisenberg spin chain with spins belonging to principal series representations of the four-dimensional conformal group. We demonstrate explicitly a relationship between this integrable spin chain and the Quantum Spectral Curve (QSC) of N = 4 SYM. Using QSC and spin chain methods, we construct Baxter equation for Q-functions of the conformal spin chain needed for computation of the anomalous dimensions of operators of the type tr( ϕ 1 J ) where ϕ 1 is one of the two scalars of the theory. For J = 3 we derive from QSC a quantization condition that fixes the relevant solution of Baxter equation. The scaling dimensions of the operators only receive contributions from wheel-like graphs. We develop integrability techniques to compute the divergent part of these graphs and use it to present the weak coupling expansion of dimensions to very high orders. Then we apply our exact equations to calculate the anomalous dimensions with J = 3 to practically unlimited precision at any coupling. These equations also describe an infinite tower of local conformal operators all carrying the same charge J = 3. The method should be applicable for any J and, in principle, to any local operators of bi-scalar theory. We show that at strong coupling the scaling dimensions can be derived from semiclassical quantization of finite gap solutions describing an integrable system of noncompact SU(2 , 2) spins. This bears similarities with the classical strings arising in the strongly coupled limit of N = 4 SYM.

  3. Objective interpretation as conforming interpretation

    Directory of Open Access Journals (Sweden)

    Lidka Rodak

    2011-12-01

    Full Text Available The practical discourse willingly uses the formula of “objective interpretation”, with no regards to its controversial nature that has been discussed in literature.The main aim of the article is to investigate what “objective interpretation” could mean and how it could be understood in the practical discourse, focusing on the understanding offered by judicature.The thesis of the article is that objective interpretation, as identified with textualists’ position, is not possible to uphold, and should be rather linked with conforming interpretation. And what this actually implies is that it is not the virtue of certainty and predictability – which are usually associated with objectivity- but coherence that makes the foundation of applicability of objectivity in law.What could be observed from the analyses, is that both the phenomenon of conforming interpretation and objective interpretation play the role of arguments in the interpretive discourse, arguments that provide justification that interpretation is not arbitrary or subjective. With regards to the important part of the ideology of legal application which is the conviction that decisions should be taken on the basis of law in order to exclude arbitrariness, objective interpretation could be read as a question “what kind of authority “supports” certain interpretation”? that is almost never free of judicial creativity and judicial activism.One can say that, objective and conforming interpretation are just another arguments used in legal discourse.

  4. Conformational kinetics of aliphatic tails

    Science.gov (United States)

    Ferrarini, Alberta; Moro, Giorgio; Nordio, Pier Luigi

    The master equation describing the random walk between sites identified with the stable conformers of a chain molecule, represents the extension to the time domain of the Rotational Isomeric State model. The asymptotic analysis of the multidimensional diffusion equation in the continuous torsional variables subjected to the configurational potential, provides a rigorous justification for the discrete models, and it supplies, without resorting to phenomenological parameters, molecular definitions of the kinetic rates for the conformational transitions occurring at each segment of the chain. The coupling between the torsional variables is fully taken into account, giving rise to cooperative effects. A complete calculation of the specific correlation functions which describe the time evolution of the angular functions probed by N.M.R. and dielectric relaxation measurements, has been performed for alkyl chains attached to a massive core. The resulting behaviour has been compared with the decay of trans and gauche populations of specific bonds, expressed in terms of suitable correlation functions whose time integrals lead quite naturally to the definition of effective kinetic constants for the conformational transitions.

  5. Anomalies, conformal manifolds, and spheres

    Energy Technology Data Exchange (ETDEWEB)

    Gomis, Jaume [Perimeter Institute for Theoretical Physics,Waterloo, Ontario, N2L 2Y5 (Canada); Hsin, Po-Shen [Department of Physics, Princeton University,Princeton, NJ 08544 (United States); Komargodski, Zohar; Schwimmer, Adam [Weizmann Institute of Science,Rehovot 76100 (Israel); Seiberg, Nathan [School of Natural Sciences, Institute for Advanced Study,Princeton, NJ 08540 (United States); Theisen, Stefan [Max-Planck-Institut für Gravitationsphysik, Albert-Einstein-Institut,14476 Golm (Germany)

    2016-03-04

    The two-point function of exactly marginal operators leads to a universal contribution to the trace anomaly in even dimensions. We study aspects of this trace anomaly, emphasizing its interpretation as a sigma model, whose target space M is the space of conformal field theories (a.k.a. the conformal manifold). When the underlying quantum field theory is supersymmetric, this sigma model has to be appropriately supersymmetrized. As examples, we consider in some detail N=(2,2) and N=(0,2) supersymmetric theories in d=2 and N=2 supersymmetric theories in d=4. This reasoning leads to new information about the conformal manifolds of these theories, for example, we show that the manifold is Kähler-Hodge and we further argue that it has vanishing Kähler class. For N=(2,2) theories in d=2 and N=2 theories in d=4 we also show that the relation between the sphere partition function and the Kähler potential of M follows immediately from the appropriate sigma models that we construct. Along the way we find several examples of potential trace anomalies that obey the Wess-Zumino consistency conditions, but can be ruled out by a more detailed analysis.

  6. CONFORMITY IN CHRIST 1. THE TRANSFORMATION PROCESS

    African Journals Online (AJOL)

    This essay investigates the notion of conformity in Christ as it is part of a compre- hensive, multilayered process of transformation. In the first part it focuses on the process of transformation in creation, re-creation, conformity, love and glory. In the second part it discusses transformation in Christ by looking at conformation and ...

  7. 40 CFR 52.938 - General conformity.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 3 2010-07-01 2010-07-01 false General conformity. 52.938 Section 52...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Kentucky § 52.938 General conformity. The General Conformity regulations were submitted on November 10, 1995, and adopted into the Kentucky State...

  8. 40 CFR 52.2133 - General conformity.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 4 2010-07-01 2010-07-01 false General conformity. 52.2133 Section 52...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) South Carolina § 52.2133 General conformity. The General Conformity regulations adopted into the South Carolina State Implementation Plan which...

  9. Conformity in Christ | Waaijman | Acta Theologica

    African Journals Online (AJOL)

    This essay investigates the notion of conformity in Christ as it is part of a comprehensive, multilayered process of transformation. In the first part it focuses on the process of transformation in creation, re-creation, conformity, love and glory. In the second part it discusses transformation in Christ by looking at conformation and ...

  10. Determination of the catalytic activity of LEOPARD syndrome-associated SHP2 mutants toward parafibromin, a bona fide SHP2 substrate involved in Wnt signaling

    International Nuclear Information System (INIS)

    Noda, Saori; Takahashi, Atsushi; Hayashi, Takeru; Tanuma, Sei-ichi; Hatakeyama, Masanori

    2016-01-01

    SHP2, encoded by the PTPN11 gene, is a protein tyrosine phosphatase that plays a key role in the proliferation of cells via RAS-ERK activation. SHP2 also promotes Wnt signaling by dephosphorylating parafibromin. Germline missense mutations of PTPN11 are found in more than half of patients with Noonan syndrome (NS) and LEOPARD syndrome (LS), both of which are congenital developmental disorders with multiple common symptoms. However, whereas NS-associated PTPN11 mutations give rise to gain-of-function SHP2 mutants, LS-associated SHP2 mutants are reportedly loss-of-function mutants. To determine the phosphatase activity of LS-associated SHP2 more appropriately, we performed an in vitro phosphatase assay using tyrosine-phosphorylated parafibromin, a biologically relevant substrate of SHP2 and the positive regulator of Wnt signaling that is activated through SHP2-mediated dephosphorylation. We found that LS-associated SHP2 mutants (Y279C, T468M, Q506P, and Q510E) exhibited a substantially reduced phosphatase activity toward parafibromin when compared with wild-type SHP2. Furthermore, each of the LS-associated mutants displayed a differential degree of decrease in phosphatase activity. Deviation of the SHP2 catalytic activity from a certain range, either too strong or too weak, may therefore lead to similar clinical outcomes in NS and LS, possibly through an imbalanced Wnt signal caused by inadequate dephosphorylation of parafibromin. - Highlights: • LS-associated SHP2 mutants dephosphorylate parafibromin on Y290, Y293, and Y315. • LS-associated SHP2 mutants display a reduced tyrosine phosphatase activity. • LS-specific SHP2-Y279C is catalytically less active than LS-specific SHP2-T468M. • NS/LS-associated SHP2-Q506P has both hyper- and hypomorphic enzymatic properties.

  11. Determination of the catalytic activity of LEOPARD syndrome-associated SHP2 mutants toward parafibromin, a bona fide SHP2 substrate involved in Wnt signaling

    Energy Technology Data Exchange (ETDEWEB)

    Noda, Saori [Division of Microbiology, Graduate School of Medicine, The University of Tokyo, Tokyo (Japan); Department of Biochemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba (Japan); Takahashi, Atsushi; Hayashi, Takeru [Division of Microbiology, Graduate School of Medicine, The University of Tokyo, Tokyo (Japan); Tanuma, Sei-ichi [Department of Biochemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba (Japan); Hatakeyama, Masanori, E-mail: mhata@m.u-tokyo.ac.jp [Division of Microbiology, Graduate School of Medicine, The University of Tokyo, Tokyo (Japan)

    2016-01-22

    SHP2, encoded by the PTPN11 gene, is a protein tyrosine phosphatase that plays a key role in the proliferation of cells via RAS-ERK activation. SHP2 also promotes Wnt signaling by dephosphorylating parafibromin. Germline missense mutations of PTPN11 are found in more than half of patients with Noonan syndrome (NS) and LEOPARD syndrome (LS), both of which are congenital developmental disorders with multiple common symptoms. However, whereas NS-associated PTPN11 mutations give rise to gain-of-function SHP2 mutants, LS-associated SHP2 mutants are reportedly loss-of-function mutants. To determine the phosphatase activity of LS-associated SHP2 more appropriately, we performed an in vitro phosphatase assay using tyrosine-phosphorylated parafibromin, a biologically relevant substrate of SHP2 and the positive regulator of Wnt signaling that is activated through SHP2-mediated dephosphorylation. We found that LS-associated SHP2 mutants (Y279C, T468M, Q506P, and Q510E) exhibited a substantially reduced phosphatase activity toward parafibromin when compared with wild-type SHP2. Furthermore, each of the LS-associated mutants displayed a differential degree of decrease in phosphatase activity. Deviation of the SHP2 catalytic activity from a certain range, either too strong or too weak, may therefore lead to similar clinical outcomes in NS and LS, possibly through an imbalanced Wnt signal caused by inadequate dephosphorylation of parafibromin. - Highlights: • LS-associated SHP2 mutants dephosphorylate parafibromin on Y290, Y293, and Y315. • LS-associated SHP2 mutants display a reduced tyrosine phosphatase activity. • LS-specific SHP2-Y279C is catalytically less active than LS-specific SHP2-T468M. • NS/LS-associated SHP2-Q506P has both hyper- and hypomorphic enzymatic properties.

  12. An Epstein-Barr virus encoded inhibitor of Colony Stimulating Factor-1 signaling is an important determinant for acute and persistent EBV infection.

    Directory of Open Access Journals (Sweden)

    Makoto Ohashi

    2012-12-01

    Full Text Available Acute Epstein-Barr virus (EBV infection is the most common cause of Infectious Mononucleosis. Nearly all adult humans harbor life-long, persistent EBV infection which can lead to development of cancers including Hodgkin Lymphoma, Burkitt Lymphoma, nasopharyngeal carcinoma, gastric carcinoma, and lymphomas in immunosuppressed patients. BARF1 is an EBV replication-associated, secreted protein that blocks Colony Stimulating Factor 1 (CSF-1 signaling, an innate immunity pathway not targeted by any other virus species. To evaluate effects of BARF1 in acute and persistent infection, we mutated the BARF1 homologue in the EBV-related herpesvirus, or lymphocryptovirus (LCV, naturally infecting rhesus macaques to create a recombinant rhLCV incapable of blocking CSF-1 (ΔrhBARF1. Rhesus macaques orally challenged with ΔrhBARF1 had decreased viral load indicating that CSF-1 is important for acute virus infection. Surprisingly, ΔrhBARF1 was also associated with dramatically lower virus setpoints during persistent infection. Normal acute viral load and normal viral setpoints during persistent rhLCV infection could be restored by Simian/Human Immunodeficiency Virus-induced immunosuppression prior to oral inoculation with ΔrhBARF1 or infection of immunocompetent animals with a recombinant rhLCV where the rhBARF1 was repaired. These results indicate that BARF1 blockade of CSF-1 signaling is an important immune evasion strategy for efficient acute EBV infection and a significant determinant for virus setpoint during persistent EBV infection.

  13. Curvature invariant characterization of event horizons of four-dimensional black holes conformal to stationary black holes

    Science.gov (United States)

    McNutt, David D.

    2017-11-01

    We introduce three approaches to generate curvature invariants that transform covariantly under a conformal transformation of a four-dimensional spacetime. For any black hole conformally related to a stationary black hole, we show how a set of conformally covariant invariants can be combined to produce a conformally covariant invariant that detects the event horizon of the conformally related black hole. As an application we consider the rotating dynamical black holes conformally related to the Kerr-Newman-Unti-Tamburino-(anti)-de Sitter spacetimes and construct an invariant that detects the conformal Killing horizon along with a second invariant that detects the conformal stationary limit surface. In addition, we present necessary conditions for a dynamical black hole to be conformally related to a stationary black hole and apply these conditions to the ingoing Kerr-Vaidya and Vaidya black hole solutions to determine if they are conformally related to stationary black holes for particular choices of the mass function. While two of the three approaches cannot be generalized to higher dimensions, we discuss the existence of a conformally covariant invariant that will detect the event horizon for any higher dimensional black hole conformally related to a stationary black hole which admits at least two conformally covariant invariants, including all vacuum spacetimes.

  14. Insights into genetic and epigenetic determinants with impact on vitamin D signaling and cancer association studies: The case of thyroid cancer

    Directory of Open Access Journals (Sweden)

    Gregoire B Morand

    2014-11-01

    Full Text Available Vitamin D is a key regulator of calcium metabolism and has been implicated as a cancer preventive agent. However, clinical studies have revealed conflicting results on its cancer preventive properties, attributed in part to multiple metabolic and regulatory factors susceptible to affect individual responses to exogenous vitamin D. Vitamin D is obtained from dietary sources and sun exposure, which depends on numerous parameters such as skin type, latitude, and lifestyle factors. Focusing on thyroid cancer, we document that genetic and epigenetic determinants can greatly impact individual response to vitamin D and may outweigh the classical clinical correlative studies that focus on sun exposure/dietary intake factors. In particular, genetic determinants innate to host intrinsic metabolic pathways such as highly polymorphic cytochromes P450s responsible for the metabolic activation of vitamin D are expressed in many organs, including the thyroid gland and can impact vitamin D interaction with its nuclear receptor (VDR in thyroid tissue. Moreover, downstream regulatory pathways in vitamin D signalling as well as VDR are also subject to wide genetic variability among human populations as shown by genome-wide studies. These genetic variations in multiple components of vitamin D pathways are critical determinants for the re-valuation of the potential preventive and anticancer properties of vitamin D in thyroid cancer.

  15. Conformal cosmological model and SNe Ia data

    International Nuclear Information System (INIS)

    Zakharov, A. F.; Pervushin, V. N.

    2012-01-01

    Now there is a huge scientific activity in astrophysical studies and cosmological ones in particular. Cosmology transforms from a pure theoretical branch of science into an observational one. All the cosmological models have to pass observational tests. The supernovae type Ia (SNe Ia) test is among the most important ones. If one applies the test to determine parameters of the standard Friedmann-Robertson-Walker cosmological model one can conclude that observations lead to the discovery of the dominance of the Λ term and as a result to an acceleration of the Universe. However, there are big mysteries connected with an origin and an essence of dark matter (DM) and the Λ term or dark energy (DE). Alternative theories of gravitation are treated as a possible solution of DM and DE puzzles. The conformal cosmological approach is one of possible alternatives to the standard ΛCDM model. As it was noted several years ago, in the framework of the conformal cosmological approach an introduction of a rigid matter can explain observational data without Λ term (or dark energy). We confirm the claim with much larger set of observational data.

  16. EBV Latency Types Adopt Alternative Chromatin Conformations

    Science.gov (United States)

    Tempera, Italo; Klichinsky, Michael; Lieberman, Paul M.

    2011-01-01

    Epstein-Barr Virus (EBV) can establish latent infections with distinct gene expression patterns referred to as latency types. These different latency types are epigenetically stable and correspond to different promoter utilization. Here we explore the three-dimensional conformations of the EBV genome in different latency types. We employed Chromosome Conformation Capture (3C) assay to investigate chromatin loop formation between the OriP enhancer and the promoters that determine type I (Qp) or type III (Cp) gene expression. We show that OriP is in close physical proximity to Qp in type I latency, and to Cp in type III latency. The cellular chromatin insulator and boundary factor CTCF was implicated in EBV chromatin loop formation. Combining 3C and ChIP assays we found that CTCF is physically associated with OriP-Qp loop formation in type I and OriP-Cp loop formation in type III latency. Mutations in the CTCF binding site located at Qp disrupt loop formation between Qp and OriP, and lead to the activation of Cp transcription. Mutation of the CTCF binding site at Cp, as well as siRNA depletion of CTCF eliminates both OriP-associated loops, indicating that CTCF plays an integral role in loop formation. These data indicate that epigenetically stable EBV latency types adopt distinct chromatin architectures that depend on CTCF and mediate alternative promoter targeting by the OriP enhancer. PMID:21829357

  17. EBV latency types adopt alternative chromatin conformations.

    Directory of Open Access Journals (Sweden)

    Italo Tempera

    2011-07-01

    Full Text Available Epstein-Barr Virus (EBV can establish latent infections with distinct gene expression patterns referred to as latency types. These different latency types are epigenetically stable and correspond to different promoter utilization. Here we explore the three-dimensional conformations of the EBV genome in different latency types. We employed Chromosome Conformation Capture (3C assay to investigate chromatin loop formation between the OriP enhancer and the promoters that determine type I (Qp or type III (Cp gene expression. We show that OriP is in close physical proximity to Qp in type I latency, and to Cp in type III latency. The cellular chromatin insulator and boundary factor CTCF was implicated in EBV chromatin loop formation. Combining 3C and ChIP assays we found that CTCF is physically associated with OriP-Qp loop formation in type I and OriP-Cp loop formation in type III latency. Mutations in the CTCF binding site located at Qp disrupt loop formation between Qp and OriP, and lead to the activation of Cp transcription. Mutation of the CTCF binding site at Cp, as well as siRNA depletion of CTCF eliminates both OriP-associated loops, indicating that CTCF plays an integral role in loop formation. These data indicate that epigenetically stable EBV latency types adopt distinct chromatin architectures that depend on CTCF and mediate alternative promoter targeting by the OriP enhancer.

  18. Conformally flat tilted Bianchi Type-V cosmological models in ...

    Indian Academy of Sciences (India)

    the complete determination of these quantities, we assume two extra conditions. First we assume that the space-time is conformally flat which leads to. 1008 .... Discussions. The model starts expanding with a big-bang at М = 0 and the expansion in the model stops at М = ∞ and = -2(Т + 2)¬. The model in general represents.

  19. Conformal symmetry inheritance in null fluid spacetimes

    International Nuclear Information System (INIS)

    Tupper, B O J; Keane, A J; Hall, G S; Coley, A A; Carot, J

    2003-01-01

    We define inheriting conformal Killing vectors for null fluid spacetimes and find the maximum dimension of the associated inheriting Lie algebra. We show that for non-conformally flat null fluid spacetimes, the maximum dimension of the inheriting algebra is seven and for conformally flat null fluid spacetimes the maximum dimension is eight. In addition, it is shown that there are two distinct classes of non-conformally flat generalized plane wave spacetimes which possess the maximum dimension, and one class in the conformally flat case

  20. Conformational analysis of six- and twelve-membered ring compounds by molecular dynamics

    DEFF Research Database (Denmark)

    Christensen, I T; Jørgensen, Flemming Steen

    1997-01-01

    . A series of methyl-substituted 1,3-dioxanes were investigated at 1000 K, and the number of chair-chair interconversions could be quantitatively correlated to the experimentally determined ring inversion barrier. Similarly, the distribution of sampled minimum-energy conformations correlated with the energy......-derived Boltzmann distribution. The macrocyclic ring system cyclododecane was subjected to an MD simulation at 1000 K and 71 different conformations could be sampled. These conformations were compared with the results of previously reported conformational analyses using stochastic search methods, and the MD method...

  1. The two conformers of acetanilide unraveled using LA-MB-FTMW spectroscopy

    Science.gov (United States)

    Cabezas, C.; Varela, M.; Caminati, W.; Mata, S.; López, J. C.; Alonso, J. L.

    2011-07-01

    Acetanilide has been investigated by laser ablation molecular beam Fourier transform microwave LA-MB-FTMW spectroscopy. The rotational spectrum of both trans and cis conformers have been analyzed to determine the rotational and 14N quadrupole coupling the constants. The spectrum of the less abundant cis conformer has been assigned for the first time. The doublets observed for this conformer have been interpreted in terms of the tunneling motion between two equivalent non-planar conformations through a small barrier in which the acetamide group and phenyl ring plane are perpendicular. The results are compared with those of the related formanilide.

  2. Conformational Control of Energy Transfer: A Mechanism for Biocompatible Nanocrystal-Based Sensors

    OpenAIRE

    Kay, Euan R.; Lee, Jungmin; Nocera, Daniel; Bawendi, Moungi G.

    2012-01-01

    Fold-up fluorophore: A new paradigm for designing self-referencing fluorescent nanosensors is demonstrated by interfacing a pH-triggered molecular conformational switch with quantum dots. Analytedependent, large-amplitude conformational motion controls the distance between the nanocrystal energy donor and an organic FRET acceptor. The result is a fluorescence signal capable of reporting pH values from individual endosomes in living cells.

  3. Mass Deformed Exact S-parameter in Conformal Theories

    DEFF Research Database (Denmark)

    Sannino, Francesco

    2010-01-01

    the existence of a universal lower bound on the opportunely normalized S parameter and explore its theoretical and phenomenological implications. Our exact results constitute an ideal framework to correctly interpret the lattice studies of the conformal window of strongly interacting theories....... leads to drastically different limiting values of S. Our results apply to any fermion matter representation and can be used as benchmark for the determination of certain relevant properties of the conformal window of any generic vector like gauge theory with fermionic matter. We finally suggest...

  4. Broadband Chirped-Pulse Fourier-Transform Microwave Spectroscopic Investigation of the Structures of Three Diethylsilane Conformers

    Science.gov (United States)

    Steber, Amanda L.; Obenchain, Daniel A.; Peebles, Rebecca A.; Peebles, Sean A.; Neill, Justin L.; Muckle, Matt T.; Pate, Brooks H.; Guirgis, Gamil A.

    2009-06-01

    The rotational spectrum of diethylsilane has been assigned using broadband chirped-pulse Fourier-transform microwave (CP-FTMW) spectroscopy. Previously, Fourier-transform microwave rotational spectra were observed using a Balle-Flygare type instrument for the ^{28}Si isotopologues of the gauche-gauche, trans-gauche, and trans-trans conformers. In the present study, a broadband microwave spectrum was obtained at the University of Virginia, taking advantage of the ability to perform deep signal averaging to increase the measurement sensitivity. To obtain a full structural determination of the conformers of this molecule, spectra for the ^{29}Si, ^{30}Si, and single ^{13}C substitutions for the gauche-gauche, the trans-gauche, and the trans-trans species were assigned. Substitution (r_s) structures and inertial fit (r_0) structures were determined and a comparison between the experimental and ab initio structures will be presented. For the ^{28}Si isotopologues, the percent differences between the experimental and ab initio rotational constants are less than 1.5% for the trans-trans and trans-gauche and are between 2.0 and 5.0% for the gauche-gauche conformer. The structural parameters will be compared between this molecule, diethylgermane and other silicon containing molecules and the relative abundances of the three conformers will be discussed. S.A. Peebles, M.M. Serafin, R.A. Peebles, G.A. Guirgis, and H.D. Stidham J. Phys. Chem. A, (2009), DOI: 10.1021/jp811049n.

  5. Structures of closed and open conformations of dimeric human ATM

    Science.gov (United States)

    Baretić, Domagoj; Pollard, Hannah K.; Fisher, David I.; Johnson, Christopher M.; Santhanam, Balaji; Truman, Caroline M.; Kouba, Tomas; Fersht, Alan R.; Phillips, Christopher; Williams, Roger L.

    2017-01-01

    ATM (ataxia-telangiectasia mutated) is a phosphatidylinositol 3-kinase–related protein kinase (PIKK) best known for its role in DNA damage response. ATM also functions in oxidative stress response, insulin signaling, and neurogenesis. Our electron cryomicroscopy (cryo-EM) suggests that human ATM is in a dynamic equilibrium between closed and open dimers. In the closed state, the PIKK regulatory domain blocks the peptide substrate–binding site, suggesting that this conformation may represent an inactive or basally active enzyme. The active site is held in this closed conformation by interaction with a long helical hairpin in the TRD3 (tetratricopeptide repeats domain 3) domain of the symmetry-related molecule. The open dimer has two protomers with only a limited contact interface, and it lacks the intermolecular interactions that block the peptide-binding site in the closed dimer. This suggests that the open conformation may be more active. The ATM structure shows the detailed topology of the regulator-interacting N-terminal helical solenoid. The ATM conformational dynamics shown by the structures represent an important step in understanding the enzyme regulation. PMID:28508083

  6. Families and degenerations of conformal field theories

    Energy Technology Data Exchange (ETDEWEB)

    Roggenkamp, D.

    2004-09-01

    In this work, moduli spaces of conformal field theories are investigated. In the first part, moduli spaces corresponding to current-current deformation of conformal field theories are constructed explicitly. For WZW models, they are described in detail, and sigma model realizations of the deformed WZW models are presented. The second part is devoted to the study of boundaries of moduli spaces of conformal field theories. For this purpose a notion of convergence of families of conformal field theories is introduced, which admits certain degenerated conformal field theories to occur as limits. To such a degeneration of conformal field theories, a degeneration of metric spaces together with additional geometric structures can be associated, which give rise to a geometric interpretation. Boundaries of moduli spaces of toroidal conformal field theories, orbifolds thereof and WZW models are analyzed. Furthermore, also the limit of the discrete family of Virasoro minimal models is investigated. (orig.)

  7. Conformational composition of neutral leucine. Matrix isolation infrared and ab initio study

    International Nuclear Information System (INIS)

    Stepanian, Stepan G.; Ivanov, Alexander Yu.; Adamowicz, Ludwik

    2013-01-01

    Highlights: • FTIR spectra of leucine isolated in argon, neon and xenon matrices are obtained. • UV irradiation is used to separate bands of the leucine conformers. • Populations of the leucine conformers is determined. - Abstract: Low-temperature matrix-isolation FTIR spectroscopy and ab initio calculations are employed to determine conformational composition of neutral leucine. The presence of three leucine conformers in the matrices is revealed. This is in agreement with the results of a detailed study of the potential energy surface of leucine which demonstrates that only five out of 105 possible conformers should have populations in the matrices larger than 2% and only three conformers, which are the ones detected in the experiment, should have populations larger than 10%. UV irradiation of the matrix samples are used to separate bands of the different conformers. We also show that the populations of the leucine conformers in the gas phase at 440 K are significantly different from the ones in matrices. The population of the lowest energy conformer in the gas phase being approximately 23% in the gas phase increases to over 64% in matrices

  8. Selection of candidate wells and optimization of conformance treatment design in the Barrancas Field using a 3D conformance simulator

    Energy Technology Data Exchange (ETDEWEB)

    Crosta, Dante; Elitseche, Luis [Repsol YPF (Argentina); Gutierrez, Mauricio; Ansah, Joe; Everett, Don [Halliburton Argentina S.A., Buenos Aires (Argentina)

    2004-07-01

    Minimizing the amount of unwanted water production is an important goal at the Barrancas field. This paper describes a selection process for candidate injection wells that is part of a pilot conformance project aimed at improving vertical injection profiles, reducing water cut in producing wells, and improving ultimate oil recovery from this field. The well selection process is based on a review of limited reservoir information available for this field to determine inter-well communications. The methodology focuses on the best use of available information, such as production and injection history, well intervention files, open hole logs and injectivity surveys. After the candidate wells were selected and potential water injection channels were identified, conformance treatment design and future performance of wells in the selected pilot area were evaluated using a new 3 -D conformance simulator, developed specifically for optimization of the design and placement of unwanted fluid shut-off treatments. Thus, when acceptable history match ing of the pilot area production was obtained, the 3 -D simulator was used to: evaluate the required volume of selected conformance treatment fluid; review expected pressures and rates during placement;. model temperature behavior; evaluate placement techniques, and forecast water cut reduction and incremental oil recovery from the producers in this simulated section of the pilot area. This paper outlines a methodology for selecting candidate wells for conformance treatments. The method involves application of several engineering tools, an integral component of which is a user-friendly conformance simulator. The use of the simulator has minimized data preparation time and allows the running of sensitivity cases quickly to explore different possible scenarios that best represent the reservoir. The proposed methodology provides an efficient means of identifying conformance problems and designing optimized solutions for these individual

  9. Conformational elasticity can facilitate TALE-DNA recognition.

    Science.gov (United States)

    Lei, Hongxing; Sun, Jiya; Baldwin, Enoch P; Segal, David J; Duan, Yong

    2014-01-01

    Sequence-programmable transcription activator-like effector (TALE) proteins have emerged as a highly efficient tool for genome engineering. Recent crystal structures depict a transition between an open unbound solenoid and more compact DNA-bound solenoid formed by the 34 amino acid repeats. How TALEs switch conformation between these two forms without substantial energetic compensation, and how the repeat-variable di-residues (RVDs) discriminate between the cognate base and other bases still remain unclear. Computational analysis on these two aspects of TALE-DNA interaction mechanism has been conducted in order to achieve a better understanding of the energetics. High elasticity was observed in the molecular dynamics simulations of DNA-free TALE structure that started from the bound conformation where it sampled a wide range of conformations including the experimentally determined apo and bound conformations. This elastic feature was also observed in the simulations starting from the apo form which suggests low free energy barrier between the two conformations and small compensation required upon binding. To analyze binding specificity, we performed free energy calculations of various combinations of RVDs and bases using Poisson-Boltzmann surface area (PBSA) and other approaches. The PBSA calculations indicated that the native RVD-base structures had lower binding free energy than mismatched structures for most of the RVDs examined. Our theoretical analyses provided new insight on the dynamics and energetics of TALE-DNA binding mechanism. © 2014 Elsevier Inc. All rights reserved.

  10. Conformational impact of structural modifications in 2-fluorocyclohexanone

    Directory of Open Access Journals (Sweden)

    Francisco A. Martins

    2017-08-01

    Full Text Available 2-Haloketones are building blocks that combine physical, chemical and biological features of materials and bioactive compounds, while organic fluorine plays a fundamental role in the design of performance organic molecules. Since these features are dependent on the three-dimensional chemical structure of a molecule, simple structural modifications can affect its conformational stability and, consequently, the corresponding physicochemical/biological property of interest. In this work, structural changes in 2-fluorocyclohexanone were theoretically studied with the aim at finding intramolecular interactions that induce the conformational equilibrium towards the axial or equatorial conformer. The interactions evaluated were hydrogen bonding, hyperconjugation, electrostatic and steric effects. While the gauche effect, originated from hyperconjugative interactions, does not appear to cause some preferences for the axial conformation of organofluorine heterocycles, more classical effects indeed rule the conformational equilibrium of the compounds. Spectroscopic parameters (NMR chemical shifts and coupling constants, which can be useful to determine the stereochemistry and the interactions operating in the series of 2-fluorocyclohexanone derivatives, were also calculated.

  11. Frustration-guided motion planning reveals conformational transitions in proteins.

    Science.gov (United States)

    Budday, Dominik; Fonseca, Rasmus; Leyendecker, Sigrid; van den Bedem, Henry

    2017-10-01

    Proteins exist as conformational ensembles, exchanging between substates to perform their function. Advances in experimental techniques yield unprecedented access to structural snapshots of their conformational landscape. However, computationally modeling how proteins use collective motions to transition between substates is challenging owing to a rugged landscape and large energy barriers. Here, we present a new, robotics-inspired motion planning procedure called dCC-RRT that navigates the rugged landscape between substates by introducing dynamic, interatomic constraints to modulate frustration. The constraints balance non-native contacts and flexibility, and instantaneously redirect the motion towards sterically favorable conformations. On a test set of eight proteins determined in two conformations separated by, on average, 7.5 Å root mean square deviation (RMSD), our pathways reduced the Cα atom RMSD to the goal conformation by 78%, outperforming peer methods. We then applied dCC-RRT to examine how collective, small-scale motions of four side-chains in the active site of cyclophilin A propagate through the protein. dCC-RRT uncovered a spatially contiguous network of residues linked by steric interactions and collective motion connecting the active site to a recently proposed, non-canonical capsid binding site 25 Å away, rationalizing NMR and multi-temperature crystallography experiments. In all, dCC-RRT can reveal detailed, all-atom molecular mechanisms for small and large amplitude motions. Source code and binaries are freely available at https://github.com/ExcitedStates/KGS/. © 2017 Wiley Periodicals, Inc.

  12. Kinetics of conformational changes of fibronectin adsorbed onto model surfaces.

    Science.gov (United States)

    Baujard-Lamotte, L; Noinville, S; Goubard, F; Marque, P; Pauthe, E

    2008-05-01

    Fibronectin (FN), a large glycoprotein found in body fluids and in the extracellular matrix, plays a key role in numerous cellular behaviours. We investigate FN adsorption onto hydrophilic bare silica and hydrophobic polystyrene (PS) surfaces using Fourier transform infrared spectroscopy-attenuated total reflection (FTIR-ATR) in aqueous medium. Adsorption kinetics using different bulk concentrations of FN were followed for 2h and the surface density of adsorbed FN and its time-dependent conformational changes were determined. When adsorption occurs onto the hydrophilic surface, FN molecules keep their native conformation independent of the adsorption conditions, but the amount of adsorbed FN increases with time and the bulk concentration. Although the protein surface density is the same on the hydrophobic PS surface, this has a strong impact on the average conformation of the adsorbed FN layer. Indeed, interfacial hydration changes induced by adsorption onto the hydrophobic surface lead to a decrease in unhydrated beta-sheet content and cause an increase in hydrated beta-strand and hydrated random domain content of adsorbed FN. This conformational change is mainly dependent on the bulk concentration. Indeed, at low bulk concentrations, the secondary structures of adsorbed FN molecules undergo strong unfolding, allowing an extended and hydrated conformation of the protein. At high bulk concentrations, the molecular packing reduces the unfolding of the stereoregular structures of the FN molecules, preventing stronger spreading of the protein.

  13. Steroid signaling system responds differently to temperature and hormone manipulation in the red-eared slider turtle (Trachemys scripta elegans), a reptile with temperature-dependent sex determination.

    Science.gov (United States)

    Ramsey, M; Crews, D

    2007-01-01

    Many reptiles, including the red-eared slider turtle (Trachemys scripta elegans), exhibit temperature-dependent sex determination (TSD). Temperature determines gonadal sex during the middle of embryogenesis, or the temperature-sensitive period (TSP), when gonadal sex is labile to both temperature and hormones--particularly estrogen. The biological actions of steroid hormones are mediated by their receptors as defined here as the classic transcriptional regulation of target genes. To elucidate estrogen action during sex determination, we examined estrogen receptor alpha (Esr1, hereafter referred to as ERalpha), estrogen receptor beta (Esr2, hereafter referred to as ERbeta), and androgen receptor (Ar, hereafter referred to as AR) expression in slider turtle gonads before, during and after the TSP, as well as following sex reversal via temperature or steroid hormone manipulation. ERalpha and AR levels spike at the female-producing temperature while ovarian sex is determined, but none of the receptors exhibited sexually dimorphic localization within the gonad prior to morphological differentiation. All three receptors respond differentially to sex-reversing treatments. When shifted to female-producing temperatures, embryos maintain ERalpha and AR expression while ERbeta is reduced. When shifted to male-producing temperatures, medullary expression of all three receptors is reduced. Feminization via estradiol (E(2)) treatment at a male-producing temperature profoundly changed the expression patterns for all three receptors. ERalpha and ERbeta redirected to the cortex in E(2)-created ovaries, while AR medullary expression was transiently reduced. Although warmer incubation temperature and estrogen result in the same endpoint (ovarian development), our results indicate different steroid signaling patterns between temperature- and estrogen-induced feminization. 2007 S. Karger AG, Basel

  14. SKR-1, a homolog of Skp1 and a member of the SCFSEL-10 complex, regulates sex-determination and LIN-12/Notch signaling in C. elegans

    Science.gov (United States)

    Killian, Darrell J.; Harvey, Elizabeth; Johnson, Peter; Otori, Muneyoshi; Mitani, Shohei; Xue, Ding

    2008-01-01

    Sex-determination in C. elegans requires regulation of gene transcription and protein activity and stability. sel-10 encodes a WD40-repeat-containing F-box protein that likely mediates the ubiquitin-mediated degradation of important sex-determination factors. Loss of sel-10 results in a mild masculinization of hermaphrodites, whereas dominant alleles of sel-10, such as sel-10(n1074), cause a more severe masculinization, including a reversal of the life versus death decision in sex-specific neurons. To investigate about how sel-10 regulates sex-determination, we conducted a sel-10(n1074) suppressor screen and isolated a weak loss-of-function allele of skr-1, one of 21 Skp1-related genes in C. elegans. Skp1, Cullin, and F-box proteins, such as SEL-10, are components of the SCF E3 ubiquitin ligase complex. We present genetic evidence that the sel-10(n1074) masculinization phenotype is dependent upon skr-1 and cul-1 activity. Furthermore, we show that the SKR-1(M140I) weak loss-of-function mutation interferes with SKR-1/SEL-10 binding. Unexpectedly, we found that the G567E substitution in SEL-10 caused by the n1074 allele impairs the binding of SEL-10 to SKR-1 and the dimerization of SEL-10, which may be important for SEL-10 function. Our results suggest that SKR-1, CUL-1 and SEL-10 constitute an SCF E3 ligase complex that plays an important role in modulating sex-determination and LIN-12/Notch signaling in C. elegans. PMID:18718460

  15. The Biological Bases of Conformity

    Science.gov (United States)

    Morgan, T. J. H.; Laland, K. N.

    2012-01-01

    Humans are characterized by an extreme dependence on culturally transmitted information and recent formal theory predicts that natural selection should favor adaptive learning strategies that facilitate effective copying and decision making. One strategy that has attracted particular attention is conformist transmission, defined as the disproportionately likely adoption of the most common variant. Conformity has historically been emphasized as significant in the social psychology literature, and recently there have also been reports of conformist behavior in non-human animals. However, mathematical analyses differ in how important and widespread they expect conformity to be, and relevant experimental work is scarce, and generates findings that are both mutually contradictory and inconsistent with the predictions of the models. We review the relevant literature considering the causation, function, history, and ontogeny of conformity, and describe a computer-based experiment on human subjects that we carried out in order to resolve ambiguities. We found that only when many demonstrators were available and subjects were uncertain was subject behavior conformist. A further analysis found that the underlying response to social information alone was generally conformist. Thus, our data are consistent with a conformist use of social information, but as subjects’ behavior is the result of both social and asocial influences, the resultant behavior may not be conformist. We end by relating these findings to an embryonic cognitive neuroscience literature that has recently begun to explore the neural bases of social learning. Here conformist transmission may be a particularly useful case study, not only because there are well-defined and tractable opportunities to characterize the biological underpinnings of this form of social learning, but also because early findings imply that humans may possess specific cognitive adaptations for effective social learning. PMID:22712006

  16. Conformance Testing: Measurement Decision Rules

    Science.gov (United States)

    Mimbs, Scott M.

    2010-01-01

    The goal of a Quality Management System (QMS) as specified in ISO 9001 and AS9100 is to provide assurance to the customer that end products meet specifications. Measuring devices, often called measuring and test equipment (MTE), are used to provide the evidence of product conformity to specified requirements. Unfortunately, processes that employ MTE can become a weak link to the overall QMS if proper attention is not given to the measurement process design, capability, and implementation. Documented "decision rules" establish the requirements to ensure measurement processes provide the measurement data that supports the needs of the QMS. Measurement data are used to make the decisions that impact all areas of technology. Whether measurements support research, design, production, or maintenance, ensuring the data supports the decision is crucial. Measurement data quality can be critical to the resulting consequences of measurement-based decisions. Historically, most industries required simplistic, one-size-fits-all decision rules for measurements. One-size-fits-all rules in some cases are not rigorous enough to provide adequate measurement results, while in other cases are overly conservative and too costly to implement. Ideally, decision rules should be rigorous enough to match the criticality of the parameter being measured, while being flexible enough to be cost effective. The goal of a decision rule is to ensure that measurement processes provide data with a sufficient level of quality to support the decisions being made - no more, no less. This paper discusses the basic concepts of providing measurement-based evidence that end products meet specifications. Although relevant to all measurement-based conformance tests, the target audience is the MTE end-user, which is anyone using MTE other than calibration service providers. Topics include measurement fundamentals, the associated decision risks, verifying conformance to specifications, and basic measurement

  17. The Biological Bases of Conformity

    Directory of Open Access Journals (Sweden)

    Thomas Joshau Henry Morgan

    2012-06-01

    Full Text Available Humans are characterized by an extreme dependence on culturally transmitted information and recent formal theory predicts that natural selection should favour adaptive learning strategies that facilitate effective use of social information in decision making. One strategy that has attracted particular attention is conformist transmission, defined as the disproportionately likely adoption of the most common variant. Conformity has historically been emphasized as significant in the social psychology literature, and recently there have also been reports of conformist behaviour in nonhuman animals. However, mathematical analyses differ in how important and widespread they expect conformity to be, and relevant experimental work is scarce, and generates findings that are both mutually contradictory and inconsistent with the predictions of the models. We review the relevant literature considering the causation, function, history and ontogeny of conformity and describe a computer-based experiment on human subjects that we carried out in order to resolve ambiguities. We found that only when many demonstrators were available and subjects were uncertain was subject behaviour conformist. A further analysis found that the underlying response to social information alone was generally conformist. Thus, our data are consistent with a conformist use of social information, but as subject’s behaviour is the result of both social and asocial influences, the resultant behaviour may not be conformist. We end by relating these findings to an embryonic cognitive neuroscience literature that has recently begun to explore the neural bases of social learning. Here conformist transmission may be a particularly useful case study, not only because there are well-defined and tractable opportunities to characterize the biological underpinnings of this form of social learning, but also because early findings imply that humans may possess specific cognitive adaptations for

  18. Conformal covariance of general relativity

    International Nuclear Information System (INIS)

    Ionescu-Pallas, N.; Gottlieb, I.

    1980-01-01

    The Einstein's equations of General Relativity are written in a conformal metric, resulting as a consequence of geometrizing the pressure forces. Accordingly, the trajectory of a test body pursues a geodetic line even inside the source of gravitational field. Moreover, the pressure, entering the perfect fluid scheme, may be replaced by a certain scalar interaction. This new manner of interpreting General Relativity is then applied to Cosmology, in order to build up a model of Universe whose static limit should coincide with that of Einstein. At the same time, the cosmological constant is connected to the scalar interaction acquiring a plausible explanation. (author)

  19. Toward TeV Conformality

    International Nuclear Information System (INIS)

    Appelquist, T.; Fleming, G. T.; Neil, E. T.; Avakian, A.; Babich, R.; Brower, R. C.; Cohen, S. D.; Rebbi, C.; Schaich, D.; Cheng, M.; Vranas, P.; Clark, M. A.; Kiskis, J.; Osborn, J. C.

    2010-01-01

    We study the chiral properties of an SU(3) gauge theory with N f massless Dirac fermions in the fundamental representation when N f is increased from 2 to 6. For N f =2, our lattice simulations lead to a value of /F 3 , where F is the Nambu-Goldstone-boson decay constant and is the chiral condensate, which agrees with the measured QCD value. For N f =6, this ratio shows significant enhancement, presaging an even larger enhancement anticipated as N f increases further, toward the critical value for transition from confinement to infrared conformality.

  20. Introduction to twisted conformal fields

    International Nuclear Information System (INIS)

    Kazama, Y.

    1988-01-01

    A pedagogical account is given of the recent developments in the theory of twisted conformal fields. Among other things, the main part of the lecture concerns the construction of the twist-emission vertex operator, which is a generalization of the fermion emission vertex in the superstring theory. Several different forms of the vertex are derived and their mutural relationships are clarified. In this paper, the authors include a brief survey of the history of the fermion emission vertex, as it offers a good perspective in which to appreciate the logical development

  1. Quantifying the passive gamma signal from spent nuclear fuel in support of determining the plutonium content in spent nuclear fuel with nondestructive assay

    Energy Technology Data Exchange (ETDEWEB)

    Fensin, Michael L [Los Alamos National Laboratory; Tobin, Steven J [Los Alamos National Laboratory; Menlove, Howard O [Los Alamos National Laboratory; Swinhoe, Martyn T [Los Alamos National Laboratory

    2009-01-01

    The objective of safeguarding nuclear material is to deter diversions of significant quantities of nuclear materials by timely monitoring and detection. There are a variety of motivations for quantifying plutonium in spent fuel (SF), by means of nondestructive assay (NDA), in order to meet this goal. These motivations include the following: strengthening the capabilities of the International Atomic Energy Agencies ability to safeguard nuclear facilities, shipper/receiver difference, input accountability at reprocessing facilities and burnup credit at repositories. Many NDA techniques exist for measuring signatures from SF; however, no single NDA technique can, in isolation, quantify elemental plutonium in SF. A study has been undertaken to determine the best integrated combination of 13 NDA techniques for characterizing Pu mass in spent fuel. This paper focuses on the development of a passive gamma measurement system in support the spent fuel assay system. Gamma ray detection for fresh nuclear fuel focuses on gamma ray emissions that directly coincide with the actinides of interest to the assay. For example, the 186-keV gamma ray is generally used for {sup 235}U assay and the 384-keV complex is generally used for assaying plutonium. In spent nuclear fuel, these signatures cannot be detected as the Compton continuum created from the fission products dominates the signal in this energy range. For SF, the measured gamma signatures from key fission products ({sup 134}Cs, {sup 137}Cs, {sup 154}Eu) are used to ascertain burnup, cooling time, and fissile content information. In this paper the Monte Carlo modeling set-up for a passive gamma spent fuel assay system will be described. The set-up of the system includes a germanium detector and an ion chamber and will be used to gain passive gamma information that will be integrated into a system for determining Pu in SF. The passive gamma signal will be determined from a library of {approx} 100 assemblies that have been

  2. Conformational analysis of 2,2'-arylmethylene bis(3-hydroxy-5,5-dimethyl-2-cyclohexene-1-one) by NMR and molecular modeling

    Energy Technology Data Exchange (ETDEWEB)

    Ferreira, Marcelle de S.; Figueroa-Villar, Jose D., E-mail: jdfv2009@gmail.com [Instituto Militar de Engenharia (IME), Rio de Janeiro, RJ (Brazil). Dept. de Quimica. Grupo de Medicina Quimica

    2014-05-15

    2,2'-arylmethylene bis(3-hydroxy-5,5-dimethyl-2-cyclohexene-1-ones) with para and ortho-R groups on the benzene ring were prepared and studied by nuclear magnetic resonance (NMR) and molecular modeling to determine their conformational exchanges. Experimental and calculated results indicated conformational interconversions in these compounds by rotation of benzene ring and slow movement of dimedone rings, leading to intramolecular hydrogen bond length variation. The presence of one R group at the ortho position on the benzene ring modifies conformational exchange, leading to disappearance of one intramolecular hydrogen bond and superposition of diverse NMR signals. The correlation of σ{sub p} values with chemical shifts, angles and atomic charges confirms that para-R groups electronic properties are involved in conformational exchange and chemical shift variance. These results will be used to study the interaction of these compounds with bio-molecules and their use as starting materials for design and synthesis of new bioactive agents. (author)

  3. Non-linear realizations of conformal symmetry and effective field theory for the pseudo-conformal universe

    International Nuclear Information System (INIS)

    Hinterbichler, Kurt; Joyce, Austin; Khoury, Justin

    2012-01-01

    The pseudo-conformal scenario is an alternative to inflation in which the early universe is described by an approximate conformal field theory on flat, Minkowski space. Some fields acquire a time-dependent expectation value, which breaks the flat space so(4,2) conformal algebra to its so(4,1) de Sitter subalgebra. As a result, weight-0 fields acquire a scale invariant spectrum of perturbations. The scenario is very general, and its essential features are determined by the symmetry breaking pattern, irrespective of the details of the underlying microphysics. In this paper, we apply the well-known coset technique to derive the most general effective lagrangian describing the Goldstone field and matter fields, consistent with the assumed symmetries. The resulting action captures the low energy dynamics of any pseudo-conformal realization, including the U(1)-invariant quartic model and the Galilean Genesis scenario. We also derive this lagrangian using an alternative method of curvature invariants, consisting of writing down geometric scalars in terms of the conformal mode. Using this general effective action, we compute the two-point function for the Goldstone and a fiducial weight-0 field, as well as some sample three-point functions involving these fields

  4. Determination of the substrate repertoire of ADAMTS2, 3, and 14 significantly broadens their functions and identifies extracellular matrix organization and TGF-β signaling as primary targets.

    Science.gov (United States)

    Bekhouche, Mourad; Leduc, Cedric; Dupont, Laura; Janssen, Lauriane; Delolme, Frederic; Vadon-Le Goff, Sandrine; Smargiasso, Nicolas; Baiwir, Dominique; Mazzucchelli, Gabriel; Zanella-Cleon, Isabelle; Dubail, Johanne; De Pauw, Edwin; Nusgens, Betty; Hulmes, David J S; Moali, Catherine; Colige, Alain

    2016-05-01

    A disintegrin and metalloproteinase with thrombospondin type I motif (ADAMTS)2, 3, and 14 are collectively named procollagen N-proteinases (pNPs) because of their specific ability to cleave the aminopropeptide of fibrillar procollagens. Several reports also indicate that they could be involved in other biological processes, such as blood coagulation, development, and male fertility, but the potential substrates associated with these activities remain unknown. Using the recently described N-terminal amine isotopic labeling of substrate approach, we analyzed the secretomes of human fibroblasts and identified 8, 17, and 22 candidate substrates for ADAMTS2, 3, and 14, respectively. Among these newly identified substrates, many are components of the extracellular matrix and/or proteins related to cell signaling such as latent TGF-β binding protein 1, TGF-β RIII, and dickkopf-related protein 3. Candidate substrates for the 3 ADAMTS have been biochemically validated in different contexts, and the implication of ADAMTS2 in the control of TGF-β activity has been further demonstrated in human fibroblasts. Finally, the cleavage site specificity was assessed showing a clear and unique preference for nonpolar or slightly hydrophobic amino acids. This work shows that the activities of the pNPs extend far beyond the classically reported processing of the aminopropeptide of fibrillar collagens and that they should now be considered as multilevel regulators of matrix deposition and remodeling.-Bekhouche, M., Leduc, C., Dupont, L., Janssen, L., Delolme, F., Vadon-Le Goff, S., Smargiasso, N., Baiwir, D., Mazzucchelli, G., Zanella-Cleon, I., Dubail, J., De Pauw, E., Nusgens, B., Hulmes, D. J. S., Moali, C., Colige, A. Determination of the substrate repertoire of ADAMTS2, 3, and 14 significantly broadens their functions and identifies extracellular matrix organization and TGF-β signaling as primary targets. © FASEB.

  5. Generative Models of Conformational Dynamics

    Science.gov (United States)

    Langmead, Christopher James

    2014-01-01

    Atomistic simulations of the conformational dynamics of proteins can be performed using either Molecular Dynamics or Monte Carlo procedures. The ensembles of three-dimensional structures produced during simulation can be analyzed in a number of ways to elucidate the thermodynamic and kinetic properties of the system. The goal of this chapter is to review both traditional and emerging methods for learning generative models from atomistic simulation data. Here, the term ‘generative’ refers to a model of the joint probability distribution over the behaviors of the constituent atoms. In the context of molecular modeling, generative models reveal the correlation structure between the atoms, and may be used to predict how the system will respond to structural perturbations. We begin by discussing traditional methods, which produce multivariate Gaussian models. We then discuss GAMELAN (GrAphical Models of Energy LANdscapes), which produces generative models of complex, non-Gaussian conformational dynamics (e.g., allostery, binding, folding, etc) from long timescale simulation data. PMID:24446358

  6. On bidimensional Lagrangian conformal models

    International Nuclear Information System (INIS)

    Lazzarini, S.

    1990-04-01

    The main topic of this thesis is the study of Conformal Field Theories defined on an arbitrary compact Riemann surface without boundary. The Beltrami parametrization of complexe structures endowing such a surface provides a local bidimensional diffeomorphism invariance of the theory and the holomorphic factorization. The perturbative quantization a la Feynman is then constrained by local factorized Ward identities. The renormalization is analysed in the Esptein-Glaser scheme. A first part deals with the simplest free field models where one checks the interesting conjecture that renormalized perturbative expansions could be resumed by a Polyakov's formula which is a Wess-Zumino action for the diffeomorphism anomaly. For a higher genus surface, only a differential version is proposed. The second part of this thesis is devoted to the characterization of some observables of the free bosonic string in the corresponding gauge theory with the aid of the nilpotent Slavnov s-operator. It is conjectured that part of the observables of this theory is labelled by the local cohomology of s modulo d and corresponds to the vertex operators, as it is verified for the tachyon vertex in the conformal gauge [fr

  7. Focused conformational sampling in proteins

    Science.gov (United States)

    Bacci, Marco; Langini, Cassiano; Vymětal, Jiří; Caflisch, Amedeo; Vitalis, Andreas

    2017-11-01

    A detailed understanding of the conformational dynamics of biological molecules is difficult to obtain by experimental techniques due to resolution limitations in both time and space. Computer simulations avoid these in theory but are often too short to sample rare events reliably. Here we show that the progress index-guided sampling (PIGS) protocol can be used to enhance the sampling of rare events in selected parts of biomolecules without perturbing the remainder of the system. The method is very easy to use as it only requires as essential input a set of several features representing the parts of interest sufficiently. In this feature space, new states are discovered by spontaneous fluctuations alone and in unsupervised fashion. Because there are no energetic biases acting on phase space variables or projections thereof, the trajectories PIGS generates can be analyzed directly in the framework of transition networks. We demonstrate the possibility and usefulness of such focused explorations of biomolecules with two loops that are part of the binding sites of bromodomains, a family of epigenetic "reader" modules. This real-life application uncovers states that are structurally and kinetically far away from the initial crystallographic structures and are also metastable. Representative conformations are intended to be used in future high-throughput virtual screening campaigns.

  8. Structures of the NLRP14 pyrin domain reveal a conformational switch mechanism regulating its molecular interactions

    International Nuclear Information System (INIS)

    Eibl, Clarissa; Hessenberger, Manuel; Wenger, Julia; Brandstetter, Hans

    2014-01-01

    Pyrin domains (PYDs) recruit downstream effector molecules in NLR signalling. A specific charge-relay system suggests a the formation of a signalling complex involving a PYD dimer. The cytosolic tripartite NLR receptors serve as important signalling platforms in innate immunity. While the C-terminal domains act as sensor and activation modules, the N-terminal death-like domain, e.g. the CARD or pyrin domain, is thought to recruit downstream effector molecules by homotypic interactions. Such homotypic complexes have been determined for all members of the death-domain superfamily except for pyrin domains. Here, crystal structures of human NLRP14 pyrin-domain variants are reported. The wild-type protein as well as the clinical D86V mutant reveal an unexpected rearrangement of the C-terminal helix α6, resulting in an extended α5/6 stem-helix. This reordering mediates a novel symmetric pyrin-domain dimerization mode. The conformational switching is controlled by a charge-relay system with a drastic impact on protein stability. How the identified charge relay allows classification of NLRP receptors with respect to distinct recruitment mechanisms is discussed

  9. ERP correlates of social conformity in a line judgment task

    Directory of Open Access Journals (Sweden)

    Chen Jing

    2012-05-01

    Full Text Available Abstract Background Previous research showed that individuals have a natural tendency to conform to others. This study investigated the temporal characteristics of neural processing involved in social conformity by recording participants’ brain potentials in performing a line judgment task. After making his initial choice, a participant was presented with the choices of four same-sex group members, which could be congruent or highly or moderately incongruent with the participant’s own choice. The participant was then immediately given a second opportunity to respond to the same stimulus. Results Participants were more likely to conform to the group members by changing their initial choices when these choices were in conflict with the group’s choices, and this behavioral adjustment occurred more often as the level of incongruence increased. Electrophysiologically, group choices that were incongruent with the participant’s choice elicited more negative-going medial frontal negativity (MFN, a component associated with processing expectancy violation, than those that were congruent with the participant’s choice, and the size of this effect increased as the level of incongruence increased. Moreover, at both levels of incongruence, the MFN responses were more negative-going for incongruent trials in which participants subsequently performed behavioral adjustment than for trials in which they stuck to their initial choices. Furthermore, over individual participants, participants who were more likely to conform to others (i.e., changing their initial choices exhibited stronger MFN effect than individuals who were more independent. Conclusions These findings suggest that incongruence with group choices or opinions can elicit brain responses that are similar to those elicited by violation of non-social expectancy in outcome evaluation and performance monitoring, and these brain signals are utilized in the following behavioral adjustment. The

  10. Conformational Fluctuations in G-Protein-Coupled Receptors

    Science.gov (United States)

    Brown, Michael F.

    2014-03-01

    G-protein-coupled receptors (GPCRs) comprise almost 50% of pharmaceutical drug targets, where rhodopsin is an important prototype and occurs naturally in a lipid membrane. Rhodopsin photoactivation entails 11-cis to all-trans isomerization of the retinal cofactor, yielding an equilibrium between inactive Meta-I and active Meta-II states. Two important questions are: (1) Is rhodopsin is a simple two-state switch? Or (2) does isomerization of retinal unlock an activated conformational ensemble? For an ensemble-based activation mechanism (EAM) a role for conformational fluctuations is clearly indicated. Solid-state NMR data together with theoretical molecular dynamics (MD) simulations detect increased local mobility of retinal after light activation. Resultant changes in local dynamics of the cofactor initiate large-scale fluctuations of transmembrane helices that expose recognition sites for the signal-transducing G-protein. Time-resolved FTIR studies and electronic spectroscopy further show the conformational ensemble is strongly biased by the membrane lipid composition, as well as pH and osmotic pressure. A new flexible surface model (FSM) describes how the curvature stress field of the membrane governs the energetics of active rhodopsin, due to the spontaneous monolayer curvature of the lipids. Furthermore, influences of osmotic pressure dictate that a large number of bulk water molecules are implicated in rhodopsin activation. Around 60 bulk water molecules activate rhodopsin, which is much larger than the number of structural waters seen in X-ray crystallography, or inferred from studies of bulk hydrostatic pressure. Conformational selection and promoting vibrational motions of rhodopsin lead to activation of the G-protein (transducin). Our biophysical data give a paradigm shift in understanding GPCR activation. The new view is: dynamics and conformational fluctuations involve an ensemble of substates that activate the cognate G-protein in the amplified visual

  11. The platelet-derived growth factor signaling system in snapping turtle embryos, Chelydra serpentina: potential role in temperature-dependent sex determination and testis development.

    Science.gov (United States)

    Rhen, Turk; Jangula, Adam; Schroeder, Anthony; Woodward-Bosh, Rikki

    2009-05-01

    The platelet-derived growth factor (Pdgf) signaling system is known to play a significant role during embryonic and postnatal development of testes in mammals and birds. In contrast, genes that comprise the Pdgf system in reptiles have never been cloned or studied in any tissue, let alone developing gonads. To explore the potential role of PDGF ligands and their receptors during embryogenesis, we cloned cDNA fragments of Pdgf-A, Pdgf-B, and receptors PdgfR-alpha and PdgfR-beta in the snapping turtle, a reptile with temperature-dependent sex determination (TSD). We then compared gene expression profiles in gonads from embryos incubated at a male-producing temperature to those from embryos at a female-producing temperature, as well as between hatchling testes and ovaries. Expression of Pdgf-B mRNA in embryonic gonads was significantly higher at a male temperature than at a female temperature, but there was no difference between hatchling testes and ovaries. This developmental pattern was reversed for Pdgf-A and PdgfR-alpha mRNA: expression of these genes did not differ in embryos, but diverged in hatchling testes and ovaries. Levels of PdgfR-beta mRNA in embryonic gonads were not affected by temperature and did not differ between testes and ovaries. However, expression of both receptors increased at least an order of magnitude from the embryonic to the post-hatching period. Finally, we characterized expression of these genes in several other embryonic tissues. The brain, heart, and liver displayed unique expression patterns that distinguished these tissues from each other and from intestine, lung, and muscle. Incubation temperature had a significant effect on expression of PdgfR-alpha and PdgfR-beta in the heart but not other tissues. Together, these findings demonstrate that temperature has tissue specific effects on the Pdgf system and suggest that Pdgf signaling is involved in sex determination and the ensuing differentiation of testes in the snapping turtle.

  12. Group quenching and galactic conformity at low redshift

    Science.gov (United States)

    Treyer, M.; Kraljic, K.; Arnouts, S.; de la Torre, S.; Pichon, C.; Dubois, Y.; Vibert, D.; Milliard, B.; Laigle, C.; Seibert, M.; Brown, M. J. I.; Grootes, M. W.; Wright, A. H.; Liske, J.; Lara-Lopez, M. A.; Bland-Hawthorn, J.

    2018-06-01

    We quantify the quenching impact of the group environment using the spectroscopic survey Galaxy and Mass Assembly to z ˜ 0.2. The fraction of red (quiescent) galaxies, whether in groups or isolated, increases with both stellar mass and large-scale (5 Mpc) density. At fixed stellar mass, the red fraction is on average higher for satellites of red centrals than of blue (star-forming) centrals, a galactic conformity effect that increases with density. Most of the signal originates from groups that have the highest stellar mass, reside in the densest environments, and have massive, red only centrals. Assuming a colour-dependent halo-to-stellar-mass ratio, whereby red central galaxies inhabit significantly more massive haloes than blue ones of the same stellar mass, two regimes emerge more distinctly: at log (Mhalo/M⊙) ≲ 13, central quenching is still ongoing, conformity is no longer existent, and satellites and group centrals exhibit the same quenching excess over field galaxies at all mass and density, in agreement with the concept of `group quenching'; at log (Mh/M⊙) ≳ 13, a cut-off that sets apart massive (log (M⋆/M⊙) > 11), fully quenched group centrals, conformity is meaningless, and satellites undergo significantly more quenching than their counterparts in smaller haloes. The latter effect strongly increases with density, giving rise to the density-dependent conformity signal when both regimes are mixed. The star formation of blue satellites in massive haloes is also suppressed compared to blue field galaxies, while blue group centrals and the majority of blue satellites, which reside in low-mass haloes, show no deviation from the colour-stellar mass relation of blue field galaxies.

  13. Group quenching and galactic conformity at low redshift

    Science.gov (United States)

    Treyer, M.; Kraljic, K.; Arnouts, S.; de la Torre, S.; Pichon, C.; Dubois, Y.; Vibert, D.; Milliard, B.; Laigle, C.; Seibert, M.; Brown, M. J. I.; Grootes, M. W.; Wright, A. H.; Liske, J.; Lara-Lopez, M. A.; Bland-Hawthorn, J.

    2018-03-01

    We quantify the quenching impact of the group environment using the spectroscopic survey Galaxy and Mass Assembly (GAMA) to z ˜ 0.2. The fraction of red (quiescent) galaxies, whether in groups or isolated, increases with both stellar mass and large-scale (5 Mpc) density. At fixed stellar mass, the red fraction is on average higher for satellites of red centrals than of blue (star-forming) centrals, a galactic conformity effect that increases with density. Most of the signal originates from groups that have the highest stellar mass, reside in the densest environments, and have massive, red only centrals. Assuming a color-dependent halo-to-stellar-mass ratio, whereby red central galaxies inhabit significantly more massive halos than blue ones of the same stellar mass, two regimes emerge more distinctly: at log (Mhalo/M⊙) ≲ 13, central quenching is still ongoing, conformity is no longer existent, and satellites and group centrals exhibit the same quenching excess over field galaxies at all mass and density, in agreement with the concept of "group quenching"; at log (Mh/M⊙) ≳ 13, a cutoff that sets apart massive (log (M⋆/M⊙) > 11), fully quenched group centrals, conformity is meaningless, and satellites undergo significantly more quenching than their counterparts in smaller halos. The latter effect strongly increases with density, giving rise to the density-dependent conformity signal when both regimes are mixed. The star-formation of blue satellites in massive halos is also suppressed compared to blue field galaxies, while blue group centrals and the majority of blue satellites, which reside in low mass halos, show no deviation from the color-stellar mass relation of blue field galaxies.

  14. Conformational exchange of aromatic side chains characterized by L-optimized TROSY-selected ¹³C CPMG relaxation dispersion.

    Science.gov (United States)

    Weininger, Ulrich; Respondek, Michal; Akke, Mikael

    2012-09-01

    Protein dynamics on the millisecond time scale commonly reflect conformational transitions between distinct functional states. NMR relaxation dispersion experiments have provided important insights into biologically relevant dynamics with site-specific resolution, primarily targeting the protein backbone and methyl-bearing side chains. Aromatic side chains represent attractive probes of protein dynamics because they are over-represented in protein binding interfaces, play critical roles in enzyme catalysis, and form an important part of the core. Here we introduce a method to characterize millisecond conformational exchange of aromatic side chains in selectively (13)C labeled proteins by means of longitudinal- and transverse-relaxation optimized CPMG relaxation dispersion. By monitoring (13)C relaxation in a spin-state selective manner, significant sensitivity enhancement can be achieved in terms of both signal intensity and the relative exchange contribution to transverse relaxation. Further signal enhancement results from optimizing the longitudinal relaxation recovery of the covalently attached (1)H spins. We validated the L-TROSY-CPMG experiment by measuring fast folding-unfolding kinetics of the small protein CspB under native conditions. The determined unfolding rate matches perfectly with previous results from stopped-flow kinetics. The CPMG-derived chemical shift differences between the folded and unfolded states are in excellent agreement with those obtained by urea-dependent chemical shift analysis. The present method enables characterization of conformational exchange involving aromatic side chains and should serve as a valuable complement to methods developed for other types of protein side chains.

  15. Conformal symmetries of FRW accelerating cosmologies

    International Nuclear Information System (INIS)

    Kehagias, A.; Riotto, A.

    2014-01-01

    We show that any accelerating Friedmann–Robertson–Walker (FRW) cosmology with equation of state w<−1/3 (and therefore not only a de Sitter stage with w=−1) exhibits three-dimensional conformal symmetry on future constant-time hypersurfaces if the bulk theory is invariant under bulk conformal Killing vectors. We also offer an alternative derivation of this result in terms of conformal Killing vectors and show that long wavelength comoving curvature perturbations of the perturbed FRW metric are just conformal Killing motions of the FRW background. We then extend the boundary conformal symmetry to the bulk for accelerating cosmologies. Our findings indicate that one can easily generate perturbations of scalar fields which are not only scale invariant, but also fully conformally invariant on super-Hubble scales. Measuring a scale-invariant power spectrum for the cosmological perturbation does not automatically imply that the universe went through a de Sitter stage

  16. Maxwell equations in conformal invariant electrodynamics

    International Nuclear Information System (INIS)

    Fradkin, E.S.; AN SSSR, Novosibirsk. Inst. Avtomatiki i Ehlektrometrii); Kozhevnikov, A.A.; Palchik, M.Ya.; Pomeransky, A.A.

    1983-01-01

    We consider a conformal invariant formulation of quantum electrodynamics. Conformal invariance is achieved with a specific mathematical construction based on the indecomposable representations of the conformal group associated with the electromagnetic potential and current. As a corolary of this construction modified expressions for the 3-point Green functions are obtained which both contain transverse parts. They make it possible to formulate a conformal invariant skeleton perturbation theory. It is also shown that the Euclidean Maxwell equations in conformal electrodynamics are manifestations of its kinematical structure: in the case of the 3-point Green functions these equations follow (up to constants) from the conformal invariance while in the case of higher Green functions they are equivalent to the equality of the kernels of the partial wave expansions. This is the manifestation of the mathematical fast of a (partial) equivalence of the representations associated with the potential, current and the field tensor. (orig.)

  17. Measuring the mechanical properties of molecular conformers

    Science.gov (United States)

    Jarvis, S. P.; Taylor, S.; Baran, J. D.; Champness, N. R.; Larsson, J. A.; Moriarty, P.

    2015-09-01

    Scanning probe-actuated single molecule manipulation has proven to be an exceptionally powerful tool for the systematic atomic-scale interrogation of molecular adsorbates. To date, however, the extent to which molecular conformation affects the force required to push or pull a single molecule has not been explored. Here we probe the mechanochemical response of two tetra(4-bromophenyl)porphyrin conformers using non-contact atomic force microscopy where we find a large difference between the lateral forces required for manipulation. Remarkably, despite sharing very similar adsorption characteristics, variations in the potential energy surface are capable of prohibiting probe-induced positioning of one conformer, while simultaneously permitting manipulation of the alternative conformational form. Our results are interpreted in the context of dispersion-corrected density functional theory calculations which reveal significant differences in the diffusion barriers for each conformer. These results demonstrate that conformational variation significantly modifies the mechanical response of even simple porpyhrins, potentially affecting many other flexible molecules.

  18. On induced action for conformal higher spins in curved background

    Energy Technology Data Exchange (ETDEWEB)

    Beccaria, Matteo, E-mail: matteo.beccaria@le.infn.it [Dipartimento di Matematica e Fisica Ennio De Giorgi, Università del Salento & INFN, Via Arnesano, 73100 Lecce (Italy); Tseytlin, Arkady A., E-mail: tseytlin@imperial.ac.uk [The Blackett Laboratory, Imperial College, London SW7 2AZ (United Kingdom)

    2017-06-15

    We continue the investigation of the structure of the action for a tower of conformal higher spin fields in non-trivial 4d background metric recently discussed in Grigoriev and Tseytlin (2016). The action is defined as an induced one from path integral of a conformal scalar field in curved background coupled to higher spin fields. We analyze in detail the dependence of the quadratic part of the induced action on the spin 1 and spin 3 fields, determining the presence of a curvature-dependent mixed spin 1–3 term. One consequence is that the pure spin 3 kinetic term cannot be gauge-invariant on its own beyond the leading term in small curvature expansion. We also compute the non-zero contribution of the 1–3 mixing term to the conformal anomaly c-coefficient. One is thus to determine all such mixing terms before addressing the question of possible vanishing of the total c-coefficient in the conformal higher spin theory.

  19. On induced action for conformal higher spins in curved background

    Directory of Open Access Journals (Sweden)

    Matteo Beccaria

    2017-06-01

    Full Text Available We continue the investigation of the structure of the action for a tower of conformal higher spin fields in non-trivial 4d background metric recently discussed in Grigoriev and Tseytlin (2016 [15]. The action is defined as an induced one from path integral of a conformal scalar field in curved background coupled to higher spin fields. We analyze in detail the dependence of the quadratic part of the induced action on the spin 1 and spin 3 fields, determining the presence of a curvature-dependent mixed spin 1–3 term. One consequence is that the pure spin 3 kinetic term cannot be gauge-invariant on its own beyond the leading term in small curvature expansion. We also compute the non-zero contribution of the 1–3 mixing term to the conformal anomaly c-coefficient. One is thus to determine all such mixing terms before addressing the question of possible vanishing of the total c-coefficient in the conformal higher spin theory.

  20. Lattice models and conformal field theories

    International Nuclear Information System (INIS)

    Saleur, H.

    1988-01-01

    Theoretical studies concerning the connection between critical physical systems and the conformal theories are reviewed. The conformal theory associated to a critical (integrable) lattice model is derived. The obtention of the central charge, critical exponents and torus partition function, using renormalization group arguments, is shown. The quantum group structure, in the integrable lattice models, and the theory of Visaro algebra representations are discussed. The relations between off-critical integrable models and conformal theories, in finite geometries, are studied

  1. Conformational changes in glycine tri- and hexapeptide

    DEFF Research Database (Denmark)

    Yakubovich, Alexander V.; Solov'yov, Ilia; Solov'yov, Andrey V.

    2006-01-01

    conformations and calculated the energy barriers for transitions between them. Using a thermodynamic approach, we have estimated the times of the characteristic transitions between these conformations. The results of our calculations have been compared with those obtained by other theoretical methods...... also investigated the influence of the secondary structure of polypeptide chains on the formation of the potential energy landscape. This analysis has been performed for the sheet and the helix conformations of chains of six amino acids....

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

    Directory of Open Access Journals (Sweden)

    Giulia Menconi

    2015-04-01

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

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

    Science.gov (United States)

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

    2015-04-01

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

  4. Geometrical formulation of the conformal Ward identity

    International Nuclear Information System (INIS)

    Kachkachi, M.

    2002-08-01

    In this paper we use deep ideas in complex geometry that proved to be very powerful in unveiling the Polyakov measure on the moduli space of Riemann surfaces and lead to obtain the partition function of perturbative string theory for 2, 3, 4 loops. Indeed, a geometrical interpretation of the conformal Ward identity in two dimensional conformal field theory is proposed: the conformal anomaly is interpreted as a deformation of the complex structure of the basic Riemann surface. This point of view is in line with the modern trend of geometric quantizations that are based on deformations of classical structures. Then, we solve the conformal Ward identity by using this geometrical formalism. (author)

  5. Fabrication challenges associated with conformal optics

    Science.gov (United States)

    Schaefer, John; Eichholtz, Richard A.; Sulzbach, Frank C.

    2001-09-01

    A conformal optic is typically an optical window that conforms smoothly to the external shape of a system platform to improve aerodynamics. Conformal optics can be on-axis, such as an ogive missile dome, or off-axis, such as in a free form airplane wing. A common example of conformal optics is the automotive head light window that conforms to the body of the car aerodynamics and aesthetics. The unusual shape of conformal optics creates tremendous challenges for design, manufacturing, and testing. This paper will discuss fabrication methods that have been successfully demonstrated to produce conformal missile domes and associated wavefront corrector elements. It will identify challenges foreseen with more complex free-form configurations. Work presented in this paper was directed by the Precision Conformal Optics Consortium (PCOT). PCOT is comprised of both industrial and academic members who teamed to develop and demonstrate conformal optical systems suitable for insertion into future military programs. The consortium was funded under DARPA agreement number MDA972-96-9-08000.

  6. Gluon amplitudes as 2 d conformal correlators

    Science.gov (United States)

    Pasterski, Sabrina; Shao, Shu-Heng; Strominger, Andrew

    2017-10-01

    Recently, spin-one wave functions in four dimensions that are conformal primaries of the Lorentz group S L (2 ,C ) were constructed. We compute low-point, tree-level gluon scattering amplitudes in the space of these conformal primary wave functions. The answers have the same conformal covariance as correlators of spin-one primaries in a 2 d CFT. The Britto-Cachazo-Feng-Witten (BCFW) recursion relation between three- and four-point gluon amplitudes is recast into this conformal basis.

  7. Noncommutative geometry and twisted conformal symmetry

    International Nuclear Information System (INIS)

    Matlock, Peter

    2005-01-01

    The twist-deformed conformal algebra is constructed as a Hopf algebra with twisted coproduct. This allows for the definition of conformal symmetry in a noncommutative background geometry. The twisted coproduct is reviewed for the Poincare algebra and the construction is then extended to the full conformal algebra. The case of Moyal-type noncommutativity of the coordinates is considered. It is demonstrated that conformal invariance need not be viewed as incompatible with noncommutative geometry; the noncommutativity of the coordinates appears as a consequence of the twisting, as has been shown in the literature in the case of the twisted Poincare algebra

  8. Unconstrained multiplet in N=2 conformal supergravity

    International Nuclear Information System (INIS)

    Hayashi, Masahito; Uehara, Shozo.

    1985-02-01

    An unconstrained (general) multiplet was studied in N = 2 conformal supergravity. Transformation law, embedding formula and multiplication rule are explicitly presented at the linearized level. (author)

  9. Superintegrability of d-dimensional conformal blocks

    International Nuclear Information System (INIS)

    Isachenkov, Mikhail

    2016-02-01

    We observe that conformal blocks of scalar 4-point functions in a d-dimensional conformal field theory can mapped to eigenfunctions of a 2-particle hyperbolic Calogero-Sutherland Hamiltonian. The latter describes two coupled Poeschl-Teller particles. Their interaction, whose strength depends smoothly on the dimension d, is known to be superintegrable. Our observation enables us to exploit the rich mathematical literature on Calogero-Sutherland models in deriving various results for conformal field theory. These include an explicit construction of conformal blocks in terms of Heckman-Opdam hypergeometric functions and a remarkable duality that relates the blocks of theories in different dimensions.

  10. Superintegrability of d-dimensional conformal blocks

    Energy Technology Data Exchange (ETDEWEB)

    Isachenkov, Mikhail [Weizmann Institute of Science, Rehovot (Israel). Dept. of Particle Physics and Astronomy; Schomerus, Volker [DESY Theory Group, Hamburg (Germany)

    2016-02-15

    We observe that conformal blocks of scalar 4-point functions in a d-dimensional conformal field theory can mapped to eigenfunctions of a 2-particle hyperbolic Calogero-Sutherland Hamiltonian. The latter describes two coupled Poeschl-Teller particles. Their interaction, whose strength depends smoothly on the dimension d, is known to be superintegrable. Our observation enables us to exploit the rich mathematical literature on Calogero-Sutherland models in deriving various results for conformal field theory. These include an explicit construction of conformal blocks in terms of Heckman-Opdam hypergeometric functions and a remarkable duality that relates the blocks of theories in different dimensions.

  11. Rotational Spectroscopy Unveils Eleven Conformers of Adrenaline

    Science.gov (United States)

    Cabezas, C.; Cortijo, V.; Mata, S.; Lopez, J. C.; Alonso, J. L.

    2013-06-01

    Recent improvements in our LA-MB-FTMW instrumentation have allowed the characterization of eleven and eight conformers for the neurotransmitters adrenaline and noradrenaline respectively. The observation of this rich conformational behavior is in accordance with the recent observation of seven conformers for dopamine and in sharp contrast with the conformational reduction proposed for catecholamines. C. Cabezas, I. Peña, J. C. López, J. L. Alonso J. Phys. Chem. Lett. 2013, 4, 486. H. Mitsuda, M. Miyazaki, I. B. Nielsen, P. Carcabal,C. Dedonder, C. Jouvet, S. Ishiuchi, M. Fujii J. Phys. Chem. Lett. 2010, 1, 1130.

  12. Conformal maps between pseudo-Finsler spaces

    Science.gov (United States)

    Voicu, Nicoleta

    The paper aims to initiate a systematic study of conformal mappings between Finsler spacetimes and, more generally, between pseudo-Finsler spaces. This is done by extending several results in pseudo-Riemannian geometry which are necessary for field-theoretical applications and by proposing a technique that reduces some problems involving pseudo-Finslerian conformal vector fields to their pseudo-Riemannian counterparts. Also, we point out, by constructing classes of examples, that conformal groups of flat (locally Minkowskian) pseudo-Finsler spaces can be much richer than both flat Finslerian and pseudo-Euclidean conformal groups.

  13. Conformal frame dependence of inflation

    International Nuclear Information System (INIS)

    Domènech, Guillem; Sasaki, Misao

    2015-01-01

    Physical equivalence between different conformal frames in scalar-tensor theory of gravity is a known fact. However, assuming that matter minimally couples to the metric of a particular frame, which we call the matter Jordan frame, the matter point of view of the universe may vary from frame to frame. Thus, there is a clear distinction between gravitational sector (curvature and scalar field) and matter sector. In this paper, focusing on a simple power-law inflation model in the Einstein frame, two examples are considered; a super-inflationary and a bouncing universe Jordan frames. Then we consider a spectator curvaton minimally coupled to a Jordan frame, and compute its contribution to the curvature perturbation power spectrum. In these specific examples, we find a blue tilt at short scales for the super-inflationary case, and a blue tilt at large scales for the bouncing case

  14. Conformable eddy current array delivery

    Science.gov (United States)

    Summan, Rahul; Pierce, Gareth; Macleod, Charles; Mineo, Carmelo; Riise, Jonathan; Morozov, Maxim; Dobie, Gordon; Bolton, Gary; Raude, Angélique; Dalpé, Colombe; Braumann, Johannes

    2016-02-01

    The external surface of stainless steel containers used for the interim storage of nuclear material may be subject to Atmospherically Induced Stress Corrosion Cracking (AISCC). The inspection of such containers poses a significant challenge due to the large quantities involved; therefore, automating the inspection process is of considerable interest. This paper reports upon a proof-of-concept project concerning the automated NDT of a set of test containers containing artificially generated AISCCs. An Eddy current array probe with a conformable padded surface from Eddyfi was used as the NDT sensor and end effector on a KUKA KR5 arc HW robot. A kinematically valid cylindrical raster scan path was designed using the KUKA|PRC path planning software. Custom software was then written to interface measurement acquisition from the Eddyfi hardware with the motion control of the robot. Preliminary results and analysis are presented from scanning two canisters.

  15. Conformal frame dependence of inflation

    Energy Technology Data Exchange (ETDEWEB)

    Domènech, Guillem; Sasaki, Misao, E-mail: guillem.domenech@yukawa.kyoto-u.ac.jp, E-mail: misao@yukawa.kyoto-u.ac.jp [Yukawa Institute for Theoretical Physics, Kyoto University, Kyoto 606-8502 (Japan)

    2015-04-01

    Physical equivalence between different conformal frames in scalar-tensor theory of gravity is a known fact. However, assuming that matter minimally couples to the metric of a particular frame, which we call the matter Jordan frame, the matter point of view of the universe may vary from frame to frame. Thus, there is a clear distinction between gravitational sector (curvature and scalar field) and matter sector. In this paper, focusing on a simple power-law inflation model in the Einstein frame, two examples are considered; a super-inflationary and a bouncing universe Jordan frames. Then we consider a spectator curvaton minimally coupled to a Jordan frame, and compute its contribution to the curvature perturbation power spectrum. In these specific examples, we find a blue tilt at short scales for the super-inflationary case, and a blue tilt at large scales for the bouncing case.

  16. Strings, conformal fields and topology

    International Nuclear Information System (INIS)

    Kaku, Michio

    1991-01-01

    String Theory has advanced at an astonishing pace in the last few years, and this book aims to acquaint the reader with the most active topics of research in the field. Building on the foundations laid in his Introduction to Superstrings, Professor Kaku discusses such topics as the classification of conformal string theories, knot theory, the Yang-Baxter relation, quantum groups, the non-polynominal closed string field theory, matrix models, and topological field theory. Several chapters review the fundamentals of string theory, making the presentation of the material self-contained while keeping overlap with the earlier book to a minimum. The book conveys the vitality of current research in string theory and places readers at its forefront. (orig.) With 40 figs. in 50 parts

  17. Light gauginos and conformal sequestering

    International Nuclear Information System (INIS)

    Hanaki, Kentaro; Ookouchi, Yutaka

    2011-01-01

    In a wide class of direct and semidirect gauge mediation models, it has been observed that the gaugino masses vanish at leading order. It implies that there is a hierarchy between the gaugino and sfermion masses, invoking a fine-tuning problem in the Higgs sector via radiative corrections. In this paper, we explore the possibility of solving this anomalously light gaugino problem exploiting strong conformal dynamics in the hidden sector. With a mild assumption on the anomalous dimensions of the hidden sector operators, we show that the next-to-leading order contributions to the gaugino masses can naturally be in the same order as the sfermion masses. The μ/B μ problem is also discussed.

  18. Space and Time Resolved Detection of Platelet Activation and von Willebrand Factor Conformational Changes in Deep Suspensions.

    Science.gov (United States)

    Biasetti, Jacopo; Sampath, Kaushik; Cortez, Angel; Azhir, Alaleh; Gilad, Assaf A; Kickler, Thomas S; Obser, Tobias; Ruggeri, Zaverio M; Katz, Joseph

    2017-01-01

    Tracking cells and proteins' phenotypic changes in deep suspensions is critical for the direct imaging of blood-related phenomena in in vitro replica of cardiovascular systems and blood-handling devices. This paper introduces fluorescence imaging techniques for space and time resolved detection of platelet activation, von Willebrand factor (VWF) conformational changes, and VWF-platelet interaction in deep suspensions. Labeled VWF, platelets, and VWF-platelet strands are suspended in deep cuvettes, illuminated, and imaged with a high-sensitivity EM-CCD camera, allowing detection using an exposure time of 1 ms. In-house postprocessing algorithms identify and track the moving signals. Recombinant VWF-eGFP (rVWF-eGFP) and VWF labeled with an FITC-conjugated polyclonal antibody are employed. Anti-P-Selectin FITC-conjugated antibodies and the calcium-sensitive probe Indo-1 are used to detect activated platelets. A positive correlation between the mean number of platelets detected per image and the percentage of activated platelets determined through flow cytometry is obtained, validating the technique. An increase in the number of rVWF-eGFP signals upon exposure to shear stress demonstrates the technique's ability to detect breakup of self-aggregates. VWF globular and unfolded conformations and self-aggregation are also observed. The ability to track the size and shape of VWF-platelet strands in space and time provides means to detect pro- and antithrombotic processes.

  19. Voltammetric determination of paracetamole using a glassy carbon electrode modified with Prussian Blue and a molecularly imprinted polymer, and ratiometric read-out of two signals

    International Nuclear Information System (INIS)

    Dai, Yunlong; Li, Xueyan; Lu, Xiaojing; Kan, Xianwen

    2016-01-01

    The authors report on a ratiometric electrochemical sensor for paracetamole (PR) which was fabricated by successively electropolymerizing a layer of Prussian blue (PB) and a layer of molecularly imprinted polypyrrole (MIP) on the surface of a glassy carbon electrode (GCE). The binding of PR molecules to the MIP has two effects: The first is an increase of the oxidation current for PR at 0.42 V (vs. SCE), and the second is a decrease in the current for PB (at 0.18 V) due to partial blocking of the channels which results in reduced electron transmissivity. Both currents, and in particular their ratio, can serve as analytical information. Under optimized conditions, the sensor displays enhanced sensitivity for PR in the 1.0 nM to 0.1 mM concentration range and a 0.53 nM lower limit of detection. The sensor was applied to the determination of PR in tablets and urines where it gave recoveries in the range between 94.6 and 104.9 %. This dual-signal (ratiometric) detection scheme (using electro polymerized Prussian Blue and analyte-specific MIP) in our perception has a wide scope in that it may be applied to numerous other electro active species for which specific MIP can be made available. (author)

  20. Simultaneous determination of penicillin G salts by infrared spectroscopy: Evaluation of combining orthogonal signal correction with radial basis function-partial least squares regression

    Science.gov (United States)

    Talebpour, Zahra; Tavallaie, Roya; Ahmadi, Seyyed Hamid; Abdollahpour, Assem

    2010-09-01

    In this study, a new method for the simultaneous determination of penicillin G salts in pharmaceutical mixture via FT-IR spectroscopy combined with chemometrics was investigated. The mixture of penicillin G salts is a complex system due to similar analytical characteristics of components. Partial least squares (PLS) and radial basis function-partial least squares (RBF-PLS) were used to develop the linear and nonlinear relation between spectra and components, respectively. The orthogonal signal correction (OSC) preprocessing method was used to correct unexpected information, such as spectral overlapping and scattering effects. In order to compare the influence of OSC on PLS and RBF-PLS models, the optimal linear (PLS) and nonlinear (RBF-PLS) models based on conventional and OSC preprocessed spectra were established and compared. The obtained results demonstrated that OSC clearly enhanced the performance of both RBF-PLS and PLS calibration models. Also in the case of some nonlinear relation between spectra and component, OSC-RBF-PLS gave satisfactory results than OSC-PLS model which indicated that the OSC was helpful to remove extrinsic deviations from linearity without elimination of nonlinear information related to component. The chemometric models were tested on an external dataset and finally applied to the analysis commercialized injection product of penicillin G salts.