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Sample records for conformational stability r0

  1. Microwave and infrared spectra, adjusted r0 structural parameters, conformational stabilities, vibrational assignments, and theoretical calculations of cyclobutylcarboxylic acid chloride.

    Science.gov (United States)

    Klaassen, Joshua J; Darkhalil, Ikhlas D; Deodhar, Bhushan S; Gounev, Todor K; Gurusinghe, Ranil M; Tubergen, Michael J; Groner, Peter; Durig, James R

    2013-08-01

    The FT-microwave spectrum of cyclobutylcarboxylic acid chloride, c-C4H7C(O)Cl, has been recorded and 153 transitions for the (35)Cl and (37)Cl isotopologues have been assigned for the gauche-equatorial (g-Eq) conformation. The ground state rotational constants were determined for (35)Cl [(37)Cl]: A = 4349.8429(25) [4322.0555(56)] MHz, B = 1414.8032(25) [1384.5058(25)] MHz, and C = 1148.2411(25) [1126.3546(25)] MHz. From these rotational constants and ab initio predicted parameters, adjusted r0 parameters are reported with distances (Å) rCα-C = 1.491(4), rC═O = 1.193(3), rCα-Cβ = 1.553(4), rCα-Cβ' = 1.540(4), rCγ-Cβ = 1.547(4), rCγ-Cβ' = 1.546(4), rC-Cl = 1.801(3) and angles (deg) τCγCβCβ'Cα = 30.9(5). Variable temperature (-70 to -100 °C) infrared spectra (4000 to 400 cm(-1)) were recorded in liquid xenon and the g-Eq conformer was determined the most stable form, with enthalpy differences of 91 ± 9 cm(-1) (1.09 ± 0.11 kJ/mol) for the gauche-axial (g-Ax) form and 173 ± 17 cm(-1) (2.07 ± 0.20 kJ/mol) for the trans-equatorial (t-Eq) conformer. The relative amounts at ambient temperature are 54% g-Eq, 35 ± 1% g-Ax, and 12 ± 1% t-Eq forms. Vibrational assignments have been provided for the three conformers and theoretical calculations were carried out. The results are discussed and compared to corresponding properties of related molecules.

  2. 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....

  3. Conformational stability of calreticulin

    DEFF Research Database (Denmark)

    Jørgensen, Charlotte S; Trandum, Christa; Larsen, Nanna Brink

    2005-01-01

    The conformational stability of calreticulin was investigated. Apparent unfolding temperatures (Tm) 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-...

  4. Salmon calcitonin: conformational changes and stabilizer effects

    Directory of Open Access Journals (Sweden)

    Shan-Yang Lin

    2015-11-01

    Full Text Available The therapeutic activity of peptides or protein drugs is highly dependent on their conformational structure. The protein structure is flexible and responds to external conditions, which may compromise the protein's native conformation and influence its physical and chemical stability. The physical and chemical stability of peptides or protein drugs are important characteristics of biopharmaceutical products. Calcitonin (CT is a polypeptide hormone that participates in diverse physiological functions in humans; therefore, it is a potentially useful protein for investigations of different aspects of pharmacology and drug delivery systems. Of the different types of CT available for clinical use, salmon CT (sCT is one of the most potent. In this review article, the commercially available sCT was selected as a suitable peptide candidate for the discussion of its stability and conformational changes in the aqueous and solid states using Fourier transform infrared (FTIR spectroscopic analysis under different external conditions, including pH, temperature, drying method, and added excipients. Particularly, excipients that have been optimized as stabilizers of sCT in aqueous solution and as lyophilized and spray-dried drug formulations are also discussed.

  5. Conformational stability and self-association equilibrium in biologics.

    Science.gov (United States)

    Clarkson, Benjamin R; Schön, Arne; Freire, Ernesto

    2016-02-01

    Biologics exist in equilibrium between native, partially denatured, and denatured conformational states. The population of any of these states is dictated by their Gibbs energy and can be altered by changes in physical and solution conditions. Some conformations have a tendency to self-associate and aggregate, an undesirable phenomenon in protein therapeutics. Conformational equilibrium and self-association are linked thermodynamic functions. Given that any associative reaction is concentration dependent, conformational stability studies performed at different protein concentrations can provide early clues to future aggregation problems. This analysis can be applied to the selection of protein variants or the identification of better formulation solutions. In this review, we discuss three different aggregation situations and their manifestation in the observed conformational equilibrium of a protein.

  6. Nanobody stabilization of G protein coupled receptor conformational states

    Science.gov (United States)

    Steyaert, Jan; K Kobilka, Brian

    2011-01-01

    Remarkable progress has been made in the field of G protein coupled receptor (GPCR) structural biology during the past four years. Several obstacles to generating diffraction quality crystals of GPCRs have been overcome by combining innovative methods ranging from protein engineering to lipid-based screens and microdiffraction technology. The initial GPCR structures represent energetically stable inactive-state conformations. However, GPCRs signal through different G protein isoforms or G protein-independent effectors upon ligand binding suggesting the existence of multiple ligand-specific active states. These active-state conformations are unstable in the absence of specific cytosolic signaling partners representing new challenges for structural biology. Camelid single chain antibody fragments (nanobodies) show promise for stabilizing active GPCR conformations and as chaperones for crystallogenesis. PMID:21782416

  7. Conformational mechanism for the stability of microtubule-kinetochore attachments

    CERN Document Server

    Bertalan, Zsolt; Maiato, Helder; Zapperi, Stefano

    2014-01-01

    Regulating the stability of microtubule(MT)-kinetochore attachments is fundamental to avoiding mitotic errors and ensure proper chromosome segregation during cell division. While biochemical factors involved in this process have been identified, its mechanics still needs to be better understood. Here we introduce and simulate a mechanical model of MT-kinetochore interactions in which the stability of the attachment is ruled by the geometrical conformations of curling MT-protofilaments entangled in kinetochore fibrils. The model allows us to reproduce with good accuracy in vitro experimental measurements of the detachment times of yeast kinetochores from MTs under external pulling forces. Numerical simulations suggest that geometrical features of MT-protofilaments may play an important role in the switch between stable and unstable attachments.

  8. Local/bulk determinants of conformational stability of exchangeable apolipoproteins.

    Science.gov (United States)

    Dergunov, Alexander D

    2011-09-01

    GuHCl-induced denaturation of human plasma apoA-I, apoA-II, apoA-IV, apoE3 and three recombinant apoE isoforms in solution and discoidal complexes with phosphatidylcholine (only plasma proteins) was studied. The protein conformational stability (ΔG(H(2)O)) and a slope of linear dependence of free energy of unfolding on GuHCl concentration (m-value) were estimated with the three equilibrium schemes. The data for all proteins, except apoA-II, fit with the three-state model, thus evidencing two-domain structure. The predicted folding rate of the four apoE in solution correlated with conformational stability. The dependence disappeared at the inclusion of apoA-I and apoA-IV into analysis and the m-values, adjusted for residue number in helices (m(rh)), differed between those for apoE and apoA-I/apoA-IV. However, the m(rh)-values for six proteins correlated positively with the fractional change in accessible surface area at unfolding for Phe, Lys and Asn, while negatively for Arg, Ala and Gly residues. The difference between the adjusted ΔG(rh)(H(2)O) values for apolipoproteins in complexes and in solution decreased at the increase of reduced temperature (T(obs)-T(t))/T(t). The induction of intrinsic disorder by arginine residues may be of primary importance in metabolism and function of exchangeable apolipoproteins, while their stability in nascent discoidal HDL is controlled by the physical state of phosphatidylcholine. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. Conformational stabilization of rat s-adenosylmethionine decarboxylase by putrescine.

    Science.gov (United States)

    Wada, Makiko; Shirahata, Akira

    2010-01-01

    The activity and processing of mammalian S-adenosylmethionine decarboxylase (AdoMetDC) is stimulated by putrescine. To obtain new insights into the mechanism through which putrescine stimulates AdoMetDC, we investigated conformational changes in rat prostate AdoMetDC in the presence or absence of putrescine. We examined the reactivity of purified rat prostate AdoMetDC to the SH-reagent iodoacetic acid (IAA) and its susceptibility to proteolysis in the presence or absence of putrescine using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). The activity of AdoMetDC treated with IAA in the absence of putrescine was reduced, but about 80% of its activity remained after treatment with IAA in the presence of putrescine. In the presence of putrescine, IAA incorporation was 1.9 mol IAA/mol of AdoMetDC α-subunit, while there was no incorporation of IAA in the β-subunit of AdoMetDC. In the absence of putrescine, 5.0 mol of IAA/mol of α-subunit and 0.9 mol of IAA/mol of β-subunit were incorporated. Only Cys292 and Cys310 were carboxymethylated by IAA in the presence of putrescine. In contrast, in the absence of putrescine all cysteines were carboxymethylated by IAA. In addition, putrescine slowed the rate of AdoMetDC degradation by trypsin. These results demonstrate that the conformation of AdoMetDC purified from rat prostate is stabilized by putrescine.

  10. Signatures of Conformational Stability and Oxidation Resistance in Proteomes of Pathogenic Bacteria

    Directory of Open Access Journals (Sweden)

    Anita Vidovic

    2014-06-01

    Full Text Available Protein oxidation is known to compromise vital cellular functions. Therefore, invading pathogenic bacteria must resist damage inflicted by host defenses via reactive oxygen species. Using comparative genomics and experimental approaches, we provide multiple lines of evidence that proteins from pathogenic bacteria have acquired resistance to oxidative stress by an increased conformational stability. Representative pathogens exhibited higher survival upon HSP90 inhibition and a less-oxidation-prone proteome. A proteome signature of the 46 pathogenic bacteria encompasses 14 physicochemical features related to increasing protein conformational stability. By purifying ten representative proteins, we demonstrate in vitro that proteins with a pathogen-like signature are more resistant to oxidative stress as a consequence of their increased conformational stability. A compositional signature of the pathogens’ proteomes allowed the design of protein fragments more resilient to both unfolding and carbonylation, validating the relationship between conformational stability and oxidability with implications for synthetic biology and antimicrobial strategies.

  11. Conformational Preferences and the Phase Stability of Fullerene Hexa-adducts.

    Science.gov (United States)

    Wu, San-Lien; Hong, Chen-Yang; Wu, Kuan-Yi; Lan, Shih-Ting; Hsieh, Chou-Ting; Chen, Hsin-Lung; Wang, Chien-Lung

    2016-07-20

    Molecular conformation and the assembly structure determine the spatial arrangements of the constituent units and the functions of a molecule. Although, fullerene hexa-adducts (FHAs) have been known as functional materials with great versatility, their conformational preferences and phase stability remain a complicate issue. By choosing bithiophene (T2 ) and dodecyl bithiophene (C12 T2 ) as the peripheral units of FHA, and using microscopic, scattering and diffraction characterizations, our study reveals how the intramolecular interaction and environmental stimulus affects the conformational preferences and phase stability of FHAs.

  12. Stabilities and conformational transitions of various proteases in the presence of an organic solvent.

    Science.gov (United States)

    Ogino, Hiroyasu; Gemba, Yuichi; Yutori, Yoshikazu; Doukyu, Noriyuki; Ishimi, Kosaku; Ishikawa, Haruo

    2007-01-01

    The half-life of the activity of the PST-01 protease that was secreted by organic solvent-tolerant Pseudomonas aeruginosa PST-01 was very long in the presence of methanol as compared to that in the absence of methanol. The conformational transitions of the PST-01 protease, alpha-chymotrypsin, thermolysin, and subtilisin in the presence and absence of methanol were monitored by measuring the CD spectra. The conformational stabilities of the PST-01 protease and subtilisin in the presence of methanol were higher than those in the absence of methanol. This resulted in high stability of these proteases in the presence of methanol. Furthermore, it was suggested that the organic solvent stabilities of enzymes were closely related to the secondary structure by monitoring the conformational transitions of polyamino acids, which form the particular conformations, in the presence and absence of methanol.

  13. Nanobody stabilization of G protein coupled receptor conformational states

    OpenAIRE

    Steyaert, Jan; K Kobilka, Brian

    2011-01-01

    Remarkable progress has been made in the field of G protein coupled receptor (GPCR) structural biology during the past four years. Several obstacles to generating diffraction quality crystals of GPCRs have been overcome by combining innovative methods ranging from protein engineering to lipid-based screens and microdiffraction technology. The initial GPCR structures represent energetically stable inactive-state conformations. However, GPCRs signal through different G protein isoforms or G pro...

  14. THE CONFORMATIONAL STABILITY OF THE REDOX STATES OF LIPOAMIDE DEHYDROGENASE FROM AZOTOBACTER-VINELANDII

    NARCIS (Netherlands)

    VANBERKEL, WJH; REGELINK, AG; BEINTEMA, JJ; KOK, A

    1991-01-01

    The conformational stability of holo-lipoamide and apo-lipoamide dehydrogenase from Azotobacter vinelandii was studied by thermoinactivation, unfolding and limited proteolysis. The oxidized holoenzyme is thermostable, showing a melting temperature, t(m) = 80-degrees-C. The thermal stability of the h

  15. The Swedish Zero Power Reactor R0

    Energy Technology Data Exchange (ETDEWEB)

    Landergaard, Olof; Cavallin, Kaj; Jonsson, Georg

    1961-05-15

    The reactor R0 is a critical facility built for heavy water and natural uranium or fuel of low enrichment,, The first criticality was achieved September 25, 1959. During a first period of more than two years the R0 will be operated as a bare reactor in order to simplify interpretation of results. The reactor tank is 3. 2 m high and 2. 25 m in diameter. The fuel suspension system is quite flexible in order to facilitate fuel exchange and lattice variations. The temperature of the water can be varied between about 10 and 90 C by means of a heater and a cooler placed in the external circulating system. The instrumentation of the reactor has to meet the safety requirements not only during operation but also during rearrangements of the core in the shut-down state. Therefore, the shut-down state is always defined by a certain low 'safe' moderator level in the reactor tank. A number of safety rods are normally kept above the moderator ready for action. For manual or automatic control of the reactor power a specially designed piston pump is needed, by which the moderator level is varied. The pump speed is controlled from the reactor power error by means of a Ward-Leonard system. Moderator level measurement is made by means of a water gauge with an accuracy of {+-} 0. 1 mm.

  16. Conformational Stabilization of Rat S-Adenosylmethionine Decarboxylase by Putrescine

    OpenAIRE

    和田, 牧子; 白幡, 晶

    2010-01-01

    The activity and processing of mammalian S-adenosylmethionine decarboxylase (AdoMetDC) is stimulated by putrescine. To obtain new insights into the mechanism through which putrescine stimulates AdoMetDC, we investigated conformational changes in rat prostate AdoMetDC in the presence or absence of putrescine. We examined the reactivity of purified rat prostate AdoMetDC to the SH-reagent iodoacetic acid (IAA) and its susceptibility to proteolysis in the presence or absence of putrescine using m...

  17. Monadic Operators on R0-algebras%R0代数上的monadic算子

    Institute of Scientific and Technical Information of China (English)

    辛小龙; 秦玉静; 贺鹏飞

    2016-01-01

    本文引入了monadic算子,定义和研究了monadic R0代数.在此基础上定义了monadic滤子和monadic同余,探讨了monadic滤子和monadic同余之间的一一对应关系.在monadic R0代数的全体monadic滤子集上引入了格运算和伴随对,证明了这样定义的monadic滤子格构成一个Heyting代数.通过例子说明了monadic R0代数未必构成monadic剩余格.最后给出了monadic R0代数形成monadic剩余格的一个条件.

  18. Conformational stability of triazolyl functionalized collagen triple helices.

    Science.gov (United States)

    Erdmann, Roman S; Wennemers, Helma

    2013-06-15

    Functionalized collagen is attractive for the development of synthetic biomaterials. Herein we present the functionalization of azidoproline containing collagen model peptides with various alkynes using click chemistry. The influence on the stability of the collagen triple helix of the stereochemistry of the introduced triazolyl prolines (4R or 4S), the position of their incorporation (Xaa or Yaa) and the substituents attached to them are shown. The results provide a useful guide for the optimal functionalization of collagen using click chemistry.

  19. Effect of sterically demanding substituents on the conformational stability of the collagen triple helix.

    Science.gov (United States)

    Erdmann, Roman S; Wennemers, Helma

    2012-10-17

    The effect of sterically demanding groups at proline residues on the conformational stability of the collagen triple helix was examined. The thermal stabilities (T(m) and ΔG) of eight different triple helices derived from collagen model peptides with (4R)- or (4S)-configured amidoprolines bearing either methyl or bulkier tert-butyl groups in the Xaa or Yaa position were determined and served as a relative measure for the conformational stability of the corresponding collagen triple helices. The results show that sterically demanding substituents are tolerated in the collagen triple helix when they are attached to (4R)-configured amidoprolines in the Xaa position or to (4S)-configured amidoprolines in the Yaa position. Structural studies in which the preferred conformation of (4R)- or (4S)-configured amidoproline were overlaid with the Pro and Hyp residues within a crystal structure of collagen revealed that the sterically demanding groups point to the outside of these two triple helices and thereby do not interfere with the formation of the triple helix. In all of the other examined collagen derivatives with lower stability of the triple helices, the acetyl or pivaloyl residues point toward the inside of the triple helix and clash with a residue of the neighboring strand. The results also revealed that unfavorable steric dispositions affect the conformational stability of the collagen triple helix more than unfavorable ring puckers of the proline residues. The results are useful for the design of functionalized collagen based materials.

  20. A conformal approach for the analysis of the non-linear stability of radiation cosmologies

    Energy Technology Data Exchange (ETDEWEB)

    Luebbe, Christian, E-mail: c.luebbe@ucl.ac.uk [Department of Mathematics, University College London, Gower Street, London, WC1E 6BT (United Kingdom); Department of Mathematics, University of Leicester, University Road, LE1 8RH (United Kingdom); Valiente Kroon, Juan Antonio, E-mail: j.a.valiente-kroon@qmul.ac.uk [School of Mathematical Sciences, Queen Mary, University of London, Mile End Road, London E1 4NS (United Kingdom)

    2013-01-15

    The conformal Einstein equations for a trace-free (radiation) perfect fluid are derived in terms of the Levi-Civita connection of a conformally rescaled metric. These equations are used to provide a non-linear stability result for de Sitter-like trace-free (radiation) perfect fluid Friedman-Lemaitre-Robertson-Walker cosmological models. The solutions thus obtained exist globally towards the future and are future geodesically complete. - Highlights: Black-Right-Pointing-Pointer We study the Einstein-Euler system in General Relativity using conformal methods. Black-Right-Pointing-Pointer We analyze the structural properties of the associated evolution equations. Black-Right-Pointing-Pointer We establish the non-linear stability of pure radiation cosmological models.

  1. Differential Scanning Calorimetry — A Method for Assessing the Thermal Stability and Conformation of Protein Antigen

    Science.gov (United States)

    Durowoju, Ibrahim B.; Bhandal, Kamaljit S.; Hu, Jian; Carpick, Bruce; Kirkitadze, Marina

    2017-01-01

    Differential scanning calorimetry (DSC) is an analytical technique that measures the molar heat capacity of samples as a function of temperature. In the case of protein samples, DSC profiles provide information about thermal stability, and to some extent serves as a structural “fingerprint” that can be used to assess structural conformation. It is performed using a differential scanning calorimeter that measures the thermal transition temperature (melting temperature; Tm) and the energy required to disrupt the interactions stabilizing the tertiary structure (enthalpy; ∆H) of proteins. Comparisons are made between formulations as well as production lots, and differences in derived values indicate differences in thermal stability and structural conformation. Data illustrating the use of DSC in an industrial setting for stability studies as well as monitoring key manufacturing steps are provided as proof of the effectiveness of this protocol. In comparison to other methods for assessing the thermal stability of protein conformations, DSC is cost-effective, requires few sample preparation steps, and also provides a complete thermodynamic profile of the protein unfolding process. PMID:28287565

  2. Differential Scanning Calorimetry - A Method for Assessing the Thermal Stability and Conformation of Protein Antigen.

    Science.gov (United States)

    Durowoju, Ibrahim B; Bhandal, Kamaljit S; Hu, Jian; Carpick, Bruce; Kirkitadze, Marina

    2017-03-04

    Differential scanning calorimetry (DSC) is an analytical technique that measures the molar heat capacity of samples as a function of temperature. In the case of protein samples, DSC profiles provide information about thermal stability, and to some extent serves as a structural "fingerprint" that can be used to assess structural conformation. It is performed using a differential scanning calorimeter that measures the thermal transition temperature (melting temperature; Tm) and the energy required to disrupt the interactions stabilizing the tertiary structure (enthalpy; ∆H) of proteins. Comparisons are made between formulations as well as production lots, and differences in derived values indicate differences in thermal stability and structural conformation. Data illustrating the use of DSC in an industrial setting for stability studies as well as monitoring key manufacturing steps are provided as proof of the effectiveness of this protocol. In comparison to other methods for assessing the thermal stability of protein conformations, DSC is cost-effective, requires few sample preparation steps, and also provides a complete thermodynamic profile of the protein unfolding process.

  3. Conformation and Stability of Intramolecular Telomeric G-Quadruplexes: Sequence Effects in the Loops

    Science.gov (United States)

    Sattin, Giovanna; Artese, Anna; Nadai, Matteo; Costa, Giosuè; Parrotta, Lucia; Alcaro, Stefano; Palumbo, Manlio; Richter, Sara N.

    2013-01-01

    Telomeres are guanine-rich sequences that protect the ends of chromosomes. These regions can fold into G-quadruplex structures and their stabilization by G-quadruplex ligands has been employed as an anticancer strategy. Genetic analysis in human telomeres revealed extensive allelic variation restricted to loop bases, indicating that the variant telomeric sequences maintain the ability to fold into G-quadruplex. To assess the effect of mutations in loop bases on G-quadruplex folding and stability, we performed a comprehensive analysis of mutant telomeric sequences by spectroscopic techniques, molecular dynamics simulations and gel electrophoresis. We found that when the first position in the loop was mutated from T to C or A the resulting structure adopted a less stable antiparallel topology; when the second position was mutated to C or A, lower thermal stability and no evident conformational change were observed; in contrast, substitution of the third position from A to C induced a more stable and original hybrid conformation, while mutation to T did not significantly affect G-quadruplex topology and stability. Our results indicate that allelic variations generate G-quadruplex telomeric structures with variable conformation and stability. This aspect needs to be taken into account when designing new potential anticancer molecules. PMID:24367632

  4. Conformation and stability of intramolecular telomeric G-quadruplexes: sequence effects in the loops.

    Directory of Open Access Journals (Sweden)

    Giovanna Sattin

    Full Text Available Telomeres are guanine-rich sequences that protect the ends of chromosomes. These regions can fold into G-quadruplex structures and their stabilization by G-quadruplex ligands has been employed as an anticancer strategy. Genetic analysis in human telomeres revealed extensive allelic variation restricted to loop bases, indicating that the variant telomeric sequences maintain the ability to fold into G-quadruplex. To assess the effect of mutations in loop bases on G-quadruplex folding and stability, we performed a comprehensive analysis of mutant telomeric sequences by spectroscopic techniques, molecular dynamics simulations and gel electrophoresis. We found that when the first position in the loop was mutated from T to C or A the resulting structure adopted a less stable antiparallel topology; when the second position was mutated to C or A, lower thermal stability and no evident conformational change were observed; in contrast, substitution of the third position from A to C induced a more stable and original hybrid conformation, while mutation to T did not significantly affect G-quadruplex topology and stability. Our results indicate that allelic variations generate G-quadruplex telomeric structures with variable conformation and stability. This aspect needs to be taken into account when designing new potential anticancer molecules.

  5. Contributions of a Position Amino Acid Residues to the Conformational Stability of GCN4 Leucine Zipper

    Institute of Scientific and Technical Information of China (English)

    WEI Xiang; ZENG Xian'gang; ZHOU Haimeng

    2006-01-01

    The stability of GCN4 leucine zipper and its four mutants in guanidine hydrochloride was detected to verify the contributions of different a position amino acid residues in polypeptide sequences to the forming and stability of parallel coiled coils. The changes of the circular dichroism spectra show that the displacement of the a position polar asparagine and the increase of asparagine in the GCN4 leucine zipper can reduce the α-helix content of the coiled coil structure. The mutants are less stable than the natural peptide in guanidine hydrochloride. The results show that the interaction between the polar asparagine contributes to the conformational stability of the coiled coil. Both the conformation and the number of polar residues in the coiled coil also affect the α-helix content and its resistance to the denaturant. The conclusions provide evidence describing the folding process of proteins including coiled coils in vivo.

  6. Global and Local Conformation of Human IgG Antibody Variants Rationalizes Loss of Thermodynamic Stability.

    Science.gov (United States)

    Edgeworth, Matthew J; Phillips, Jonathan J; Lowe, David C; Kippen, Alistair D; Higazi, Daniel R; Scrivens, James H

    2015-12-07

    Immunoglobulin G (IgG) monoclonal antibodies (mAbs) are a major class of medicines, with high specificity and affinity towards targets spanning many disease areas. The antibody Fc (fragment crystallizable) region is a vital component of existing antibody therapeutics, as well as many next generation biologic medicines. Thermodynamic stability is a critical property for the development of stable and effective therapeutic proteins. Herein, a combination of ion-mobility mass spectrometry (IM-MS) and hydrogen/deuterium exchange mass spectrometry (HDX-MS) approaches have been used to inform on the global and local conformation and dynamics of engineered IgG Fc variants with reduced thermodynamic stability. The changes in conformation and dynamics have been correlated with their thermodynamic stability to better understand the destabilising effect of functional IgG Fc mutations and to inform engineering of future therapeutic proteins.

  7. Stability and covergence properties of Bergman Kernel methods for numerical conformal mapping

    OpenAIRE

    Papamichael, N.; Warby, M K

    1984-01-01

    In this paper we study the stability and convergence properties of Bergman kernel methods, for the numerical conform al mapping of simply and doubly- connected domains. In particular, by using certain well-known results of Carleman, we establish a characterization of the level of instability in the methods, in terms of the geometry of the domain under consideration. We also explain how certain known convergence results can provide some theoretical justification of the observed improvement in ...

  8. Significance of bending restraints for the stability of helical polymer conformations

    Science.gov (United States)

    Williams, Matthew J.; Bachmann, Michael

    2016-06-01

    We performed parallel-tempering Monte Carlo simulations to investigate the formation and stability of helical tertiary structures for flexible and semiflexible polymers, employing a generic coarse-grained model. Structural conformations exhibit helical order with tertiary ordering into single helices, multiple helical segments organized into bundles, and disorganized helical arrangements. For both bending-restrained semiflexible and bending-unrestrained flexible helical polymers, the stability of the structural phases is discussed systematically by means of hyperphase diagrams parametrized by suitable order parameters, temperature, and torsion strength. This exploration lends insight into the restricted flexibility of biological polymers such as double-stranded DNA and proteins.

  9. Significance of bending restraints for the stability of helical polymer conformations.

    Science.gov (United States)

    Williams, Matthew J; Bachmann, Michael

    2016-06-01

    We performed parallel-tempering Monte Carlo simulations to investigate the formation and stability of helical tertiary structures for flexible and semiflexible polymers, employing a generic coarse-grained model. Structural conformations exhibit helical order with tertiary ordering into single helices, multiple helical segments organized into bundles, and disorganized helical arrangements. For both bending-restrained semiflexible and bending-unrestrained flexible helical polymers, the stability of the structural phases is discussed systematically by means of hyperphase diagrams parametrized by suitable order parameters, temperature, and torsion strength. This exploration lends insight into the restricted flexibility of biological polymers such as double-stranded DNA and proteins.

  10. Ca2+ and Mg2+ binding induce conformational stability of Calfumirin-1 from Dictyostelium discoideum

    Indian Academy of Sciences (India)

    Bairagi C Mallick; Sa-Ouk Kang; Suman Jha

    2014-05-01

    The apo-Calfumirin-1 (CAF-1) binds to Ca2+ with high affinity and also to Mg2+ with high positive cooperativity. The thermal unfolding curves of wtCAF-1 monitored at neutral pH by CD spectroscopy are reversible and show different thermal stabilities in the absence or presence of Ca2+ and Mg2+ ions. Metalfree wtCAF-1 shows greater thermal stability than EF-IV mutant protein. We observed that GdnHCl-induced unfolding of apo-wtCAF-1 monitored by CD and fluorescence spectroscopies increases co-operative folding with approximately same C values. Binding of Ca2+ and Mg2+ ions to CAF-1 dramatically altered the fluorescence and CD spectra, indicating metal ion-induced conformational changes both in the wild-type and mutant proteins. The hydrophobic probe, ANS is used to observe alteration in surface hydrophobicity of the protein in different ligation states. In apo-wtCAF-1, the exposed hydrophobic surfaces are able to bind ANS which is in contrast to the unfolded or the metal ions ligated conformations. Isothermal titration calorimetry (ITC) resultsshow two possible independent binding sites of comparable affinity for the metal ions. However, their binding to the EF-IV E helix-loop-F helix mutant apo-protein happens with different affinities. The present study demonstrates that Ca2+ or Mg2+ binding plays a possible role in the conformational stability of the protein.

  11. Effects of modified {beta}-cyclodextrin on thermal stability and conformation of lysozyme

    Energy Technology Data Exchange (ETDEWEB)

    Kamiyama, Tadashi, E-mail: kamiyama@chem.kindai.ac.jp [Department of Chemistry, School of Science and Engineering, Kinki University, Kowakae 3-4-1, Higashi-Osaka, Osaka 577-8502 (Japan); Satoh, Megumi; Tateishi, Takahiro; Nojiri, Tomoaki; Takeuchi, Daisuke; Kimura, Takayoshi [Department of Chemistry, School of Science and Engineering, Kinki University, Kowakae 3-4-1, Higashi-Osaka, Osaka 577-8502 (Japan)

    2012-03-20

    Highlights: Black-Right-Pointing-Pointer Effects of cyclodextrin on stability and conformation of lysozyme were clarified. Black-Right-Pointing-Pointer The CD influences the hydrophobic interaction of lysozyme by the inclusion. Black-Right-Pointing-Pointer The CD relatively destabilized the folded state by stabilizing the unfolded state. Black-Right-Pointing-Pointer The destabilization depends on the concentration and the substituent of CD. Black-Right-Pointing-Pointer The conformation of lysozyme was more spread at unfolded state by inclusion of CD. - Abstract: Effects of cyclic oligosaccharide cyclodextrin (CD) on stability and conformation of lysozyme were clarified thermodynamically and rheologically by DSC, viscosity, and circular dichroism measurements. The modified {beta}-CD relatively destabilized the folded state of lysozyme by stabilizing the unfolded state due to inclusion of hydrophobic part into the hydrophobic interior of CD. The order of higher destabilization effect was acetyl-{beta}-CD > methyl-{beta}-CD > hydroxypropyl-{beta}-CD. Apparent number of bound CD to unfolded state for methyl-, hydroxypropyl-, and acetyl-{beta}-CD is 6.7 {+-} 0.7, 4.2 {+-} 1.1, and 18.6 {+-} 4.3 and the binding constant is 5.5 {+-} 0.8, 6.7 {+-} 2.4, and 4.4 {+-} 1.2 L mol{sup -1}, respectively. The viscosity for unfolded state was increased with an increase in the each modified {beta}-CD concentration, suggesting that the inclusion of CD on a part of hydrophobic core at unfolded state leads to break the hydrophobic core, then lysozyme would be more spread structure. The substituent of CD can accelerate instability by directly breaking hydrogen bond and/or can restrain instability by increase in hydrophobic interaction. The fact that the each modified CDs has different destabilization effect shows a possibility to control the stability of protein by the substitution of CD.

  12. Importance of asparagine on the conformational stability and chemical reactivity of selected anti-inflammatory peptides

    Energy Technology Data Exchange (ETDEWEB)

    Soriano-Correa, Catalina, E-mail: csorico@comunidad.unam.mx [Química Computacional, Facultad de Estudios Superiores (FES)-Zaragoza, Universidad Nacional Autónoma de México (UNAM), Iztapalapa, C.P. 09230 México, D.F. (Mexico); Barrientos-Salcedo, Carolina [Laboratorio de Química Médica y Quimiogenómica, Facultad de Bioanálisis Campus Veracruz-Boca del Río, Universidad Veracruzana, C.P. 91700 Veracruz (Mexico); Campos-Fernández, Linda; Alvarado-Salazar, Andres [Química Computacional, Facultad de Estudios Superiores (FES)-Zaragoza, Universidad Nacional Autónoma de México (UNAM), Iztapalapa, C.P. 09230 México, D.F. (Mexico); Esquivel, Rodolfo O. [Departamento de Química, Universidad Autónoma Metropolitana-Iztapalapa (UAM-Iztapalapa), C.P. 09340 México, D.F. (Mexico)

    2015-08-18

    Highlights: • Asparagine plays an important role to anti-inflammatory effect of peptides. • The electron-donor substituent groups favor the formation of the hydrogen bonds, which contribute in the structural stability of peptides. • Chemical reactivity and the physicochemical features are crucial in the biological functions of peptides. - Abstract: Inflammatory response events are initiated by a complex series of molecular reactions that generate chemical intermediaries. The structure and properties of peptides and proteins are determined by the charge distribution of their side chains, which play an essential role in its electronic structure and physicochemical properties, hence on its biological functionality. The aim of this study was to analyze the effect of changing one central amino acid, such as substituting asparagine for aspartic acid, from Cys–Asn–Ser in aqueous solution, by assessing the conformational stability, physicochemical properties, chemical reactivity and their relationship with anti-inflammatory activity; employing quantum-chemical descriptors at the M06-2X/6-311+G(d,p) level. Our results suggest that asparagine plays a more critical role than aspartic acid in the structural stability, physicochemical features, and chemical reactivity of these tripeptides. Substituent groups in the side chain cause significant changes on the conformational stability and chemical reactivity, and consequently on their anti-inflammatory activity.

  13. Substituted naphthalenes: Stability, conformational flexibility and description of bonding based on ETS-NOCV method

    Science.gov (United States)

    Stanković, B.; Ostojić, B. D.; Gruden, M.; Popović, A.; Đorđević, D. S.

    2016-09-01

    For all dimethylnaphthalenes (DMNs) the transition from a planar ring conformation to a nonplanar one results in energy increase in the range 1.7-2.4 kcal/mol. There is a linear relationship between averaged rigidity constant and relative energy of DMNs. The relative stability of DMNs does not follow the aromatic stabilization based on NICS values. The ETS-NOCV analysis shows that more efficient bonding in the π-electron system is the origin of enhanced stability in laterally substituted (CH3, Cl and NO2) naphthalenes. The results for Caryl-CH3 system indicate more steric repulsion in going from 2,7-DMN to 1,8-DMN following the increase of relative energies.

  14. Rapid RNA-ligand interaction analysis through high-information content conformational and stability landscapes

    Energy Technology Data Exchange (ETDEWEB)

    Baird, Nathan J. [National Inst. of Health (NIH), Bethesda, MD (United States); Inglese, James [National Inst. of Health (NIH), Bethesda, MD (United States); Ferré-D’Amaré, Adrian R. [National Inst. of Health (NIH), Bethesda, MD (United States)

    2015-12-07

    The structure and biological properties of RNAs are a function of changing cellular conditions, but comprehensive, simultaneous investigation of the effect of multiple interacting environmental variables is not easily achieved. We have developed an efficient, high-throughput method to characterize RNA structure and thermodynamic stability as a function of multiplexed solution conditions using Förster resonance energy transfer (FRET). In a single FRET experiment using conventional quantitative PCR instrumentation, 19,400 conditions of MgCl2, ligand and temperature are analysed to generate detailed empirical conformational and stability landscapes of the cyclic diguanylate (c-di-GMP) riboswitch. This method allows rapid comparison of RNA structure modulation by cognate and non-cognate ligands. Landscape analysis reveals that kanamycin B stabilizes a non-native, idiosyncratic conformation of the riboswitch that inhibits c-di-GMP binding. Our research demonstrates that allosteric control of folding, rather than direct competition with cognate effectors, is a viable approach for pharmacologically targeting riboswitches and other structured RNA molecules.

  15. Rapid RNA-ligand interaction analysis through high-information content conformational and stability landscapes

    Science.gov (United States)

    Baird, Nathan J.; Inglese, James; Ferré-D'Amaré, Adrian R.

    2015-12-01

    The structure and biological properties of RNAs are a function of changing cellular conditions, but comprehensive, simultaneous investigation of the effect of multiple interacting environmental variables is not easily achieved. We have developed an efficient, high-throughput method to characterize RNA structure and thermodynamic stability as a function of multiplexed solution conditions using Förster resonance energy transfer (FRET). In a single FRET experiment using conventional quantitative PCR instrumentation, 19,400 conditions of MgCl2, ligand and temperature are analysed to generate detailed empirical conformational and stability landscapes of the cyclic diguanylate (c-di-GMP) riboswitch. The method allows rapid comparison of RNA structure modulation by cognate and non-cognate ligands. Landscape analysis reveals that kanamycin B stabilizes a non-native, idiosyncratic conformation of the riboswitch that inhibits c-di-GMP binding. This demonstrates that allosteric control of folding, rather than direct competition with cognate effectors, is a viable approach for pharmacologically targeting riboswitches and other structured RNA molecules.

  16. Conformational Stability of Mammalian Prion Protein Amyloid Fibrils Is Dictated by a Packing Polymorphism within the Core Region*

    Science.gov (United States)

    Cobb, Nathan J.; Apostol, Marcin I.; Chen, Shugui; Smirnovas, Vytautas; Surewicz, Witold K.

    2014-01-01

    Mammalian prion strains are believed to arise from the propagation of distinct conformations of the misfolded prion protein PrPSc. One key operational parameter used to define differences between strains has been conformational stability of PrPSc as defined by resistance to thermal and/or chemical denaturation. However, the structural basis of these stability differences is unknown. To bridge this gap, we have generated two strains of recombinant human prion protein amyloid fibrils that show dramatic differences in conformational stability and have characterized them by a number of biophysical methods. Backbone amide hydrogen/deuterium exchange experiments revealed that, in sharp contrast to previously studied strains of infectious amyloid formed from the yeast prion protein Sup35, differences in β-sheet core size do not underlie differences in conformational stability between strains of mammalian prion protein amyloid. Instead, these stability differences appear to be dictated by distinct packing arrangements (i.e. steric zipper interfaces) within the amyloid core, as indicated by distinct x-ray fiber diffraction patterns and large strain-dependent differences in hydrogen/deuterium exchange kinetics for histidine side chains within the core region. Although this study was limited to synthetic prion protein amyloid fibrils, a similar structural basis for strain-dependent conformational stability may apply to brain-derived PrPSc, especially because large strain-specific differences in PrPSc stability are often observed despite a similar size of the PrPSc core region. PMID:24338015

  17. Conformational stability of mammalian prion protein amyloid fibrils is dictated by a packing polymorphism within the core region.

    Science.gov (United States)

    Cobb, Nathan J; Apostol, Marcin I; Chen, Shugui; Smirnovas, Vytautas; Surewicz, Witold K

    2014-01-31

    Mammalian prion strains are believed to arise from the propagation of distinct conformations of the misfolded prion protein PrP(Sc). One key operational parameter used to define differences between strains has been conformational stability of PrP(Sc) as defined by resistance to thermal and/or chemical denaturation. However, the structural basis of these stability differences is unknown. To bridge this gap, we have generated two strains of recombinant human prion protein amyloid fibrils that show dramatic differences in conformational stability and have characterized them by a number of biophysical methods. Backbone amide hydrogen/deuterium exchange experiments revealed that, in sharp contrast to previously studied strains of infectious amyloid formed from the yeast prion protein Sup35, differences in β-sheet core size do not underlie differences in conformational stability between strains of mammalian prion protein amyloid. Instead, these stability differences appear to be dictated by distinct packing arrangements (i.e. steric zipper interfaces) within the amyloid core, as indicated by distinct x-ray fiber diffraction patterns and large strain-dependent differences in hydrogen/deuterium exchange kinetics for histidine side chains within the core region. Although this study was limited to synthetic prion protein amyloid fibrils, a similar structural basis for strain-dependent conformational stability may apply to brain-derived PrP(Sc), especially because large strain-specific differences in PrP(Sc) stability are often observed despite a similar size of the PrP(Sc) core region.

  18. The bound conformation of microtubule-stabilizing agents: NMR insights into the bioactive 3D structure of discodermolide and dictyostatin.

    Science.gov (United States)

    Canales, Angeles; Matesanz, Ruth; Gardner, Nicola M; Andreu, José Manuel; Paterson, Ian; Díaz, J Fernando; Jiménez-Barbero, Jesús

    2008-01-01

    A protocol based on a combination of NMR experimental data with molecular mechanics calculations and docking procedures has been employed to determine the microtubule-bound conformation of two microtubule-stabilizing agents, discodermolide (DDM) and dictyostatin (DCT). The data indicate that tubulin in assembled microtubules recognizes DDM through a conformational selection process, with minor changes in the molecular skeleton between the major conformer in water solution and that bound to assembled microtubules. For DCT, the deduced bound geometry presents some key conformation differences around certain torsion angles, with respect to the major conformer in solution, and still displays mobility even when bound. The bound conformer of DCT resembles that of DDM and provides very similar contacts with the receptor. Competition experiments indicate that both molecules compete with the taxane-binding site. A model of the binding mode of DDM and DCT to tubulin is proposed.

  19. Distinct Contribution of Electrostatics, Initial Conformational Ensemble, and Macromolecular Stability in RNA Folding

    Energy Technology Data Exchange (ETDEWEB)

    Laederach,A.; Shcherbakova, I.; Jonikas, M.; Altman, R.; Brenowitz, M.

    2007-01-01

    We distinguish the contribution of the electrostatic environment, initial conformational ensemble, and macromolecular stability on the folding mechanism of a large RNA using a combination of time-resolved 'Fast Fenton' hydroxyl radical footprinting and exhaustive kinetic modeling. This integrated approach allows us to define the folding landscape of the L-21 Tetrahymena thermophila group I intron structurally and kinetically from its earliest steps with unprecedented accuracy. Distinct parallel pathways leading the RNA to its native form upon its Mg2+-induced folding are observed. The structures of the intermediates populating the pathways are not affected by variation of the concentration and type of background monovalent ions (electrostatic environment) but are altered by a mutation that destabilizes one domain of the ribozyme. Experiments starting from different conformational ensembles but folding under identical conditions show that whereas the electrostatic environment modulates molecular flux through different pathways, the initial conformational ensemble determines the partitioning of the flux. This study showcases a robust approach for the development of kinetic models from collections of local structural probes.

  20. Assessing the stability of alanine-based helices by conformer-selective IR spectroscopy.

    Science.gov (United States)

    Hoffmann, Waldemar; Marianski, Mateusz; Warnke, Stephan; Seo, Jongcheol; Baldauf, Carsten; von Helden, Gert; Pagel, Kevin

    2016-07-20

    Polyalanine based peptides that carry a lysine at the C-terminus ([Ac-AlanLys + H](+)) are known to form α-helices in the gas phase. Three factors contribute to the stability of these helices: (i) the interaction between the helix macro dipole and the charge, (ii) the capping of dangling C[double bond, length as m-dash]O groups by lysine and (iii) the cooperative hydrogen bond network. In previous studies, the influence of the interaction between the helix dipole and the charge as well as the impact of the capping was studied intensively. Here, we complement these findings by systematically assessing the third parameter, the H-bond network. In order to selectively remove one H-bond along the backbone, we use amide-to-ester substitutions. The resulting depsi peptides were analyzed by ion-mobility and m/z-selective infrared spectroscopy as well as theoretical calculations. Our results indicate that peptides which contain only one ester bond still maintain the helical conformation. We conclude that the interaction between the charge and the helix macro-dipole is most crucial for the formation of the α-helical conformation and a single backbone H-bond has only little influence on the overall stability.

  1. Ligand specificity and conformational stability of human fatty acid-binding proteins.

    Science.gov (United States)

    Zimmerman, A W; van Moerkerk, H T; Veerkamp, J H

    2001-09-01

    Fatty acid binding proteins (FABPs) are small cytosolic proteins with virtually identical backbone structures that facilitate the solubility and intracellular transport of fatty acids. At least eight different types of FABP occur, each with a specific tissue distribution and possibly with a distinct function. To define the functional characteristics of all eight human FABPs, viz. heart (H), brain (B), myelin (M), adipocyte (A), epidermal (E), intestinal (I), liver (L) and ileal lipid-binding protein (I-LBP), we studied their ligand specificity, their conformational stability and their immunological crossreactivity. Additionally, binding of bile acids to I-LBP was studied. The FABP types showed differences in fatty acid binding affinity. Generally, the affinity for palmitic acid was lower than for oleic and arachidonic acid. All FABP types, except E-FABP, I-FABP and I-LBP interacted with 1-anilinonaphtalene-8-sulphonic acid (ANS). Only L-FABP, I-FABP and M-FABP showed binding of 11-((5-dimethylaminonaphtalene-1-sulfonyl)amino)undecanoic acid (DAUDA). I-LBP showed increasing binding of bile acids in the order taurine-conjugated>glycine-conjugated>unconjugated bile acids. A hydroxylgroup of bile acids at position 7 decreased and at position 12 increased the binding affinity to I-LBP. The fatty acid-binding affinity and the conformation of FABP types were differentially affected in the presence of urea. Our results demonstrate significant differences in ligand binding, conformational stability and surface properties between different FABP types which may point to a specific function in certain cells and tissues. The preference of I-LBP (but not L-FABP) for conjugated bile acids is in accordance with a specific role in bile acid reabsorption in the ileum.

  2. Cyclic AMP analog blocks kinase activation by stabilizing inactive conformation: conformational selection highlights a new concept in allosteric inhibitor design.

    Science.gov (United States)

    Badireddy, Suguna; Yunfeng, Gao; Ritchie, Mark; Akamine, Pearl; Wu, Jian; Kim, Choel W; Taylor, Susan S; Qingsong, Lin; Swaminathan, Kunchithapadam; Anand, Ganesh S

    2011-03-01

    The regulatory (R) subunit of protein kinase A serves to modulate the activity of protein kinase A in a cAMP-dependent manner and exists in two distinct and structurally dissimilar, end point cAMP-bound "B" and C-subunit-bound "H"-conformations. Here we report mechanistic details of cAMP action as yet unknown through a unique approach combining x-ray crystallography with structural proteomics approaches, amide hydrogen/deuterium exchange and ion mobility mass spectrometry, applied to the study of a stereospecific cAMP phosphorothioate analog and antagonist((Rp)-cAMPS). X-ray crystallography shows cAMP-bound R-subunit in the B form but surprisingly the antagonist Rp-cAMPS-bound R-subunit crystallized in the H conformation, which was previously assumed to be induced only by C-subunit-binding. Apo R-subunit crystallized in the B form as well but amide exchange mass spectrometry showed large differences between apo, agonist and antagonist-bound states of the R-subunit. Further ion mobility reveals the apo R-subunit as an ensemble of multiple conformations with collisional cross-sectional areas spanning both the agonist and antagonist-bound states. Thus contrary to earlier studies that explained the basis for cAMP action through "induced fit" alone, we report evidence for conformational selection, where the ligand-free apo form of the R-subunit exists as an ensemble of both B and H conformations. Although cAMP preferentially binds the B conformation, Rp-cAMPS interestingly binds the H conformation. This reveals the unique importance of the equatorial oxygen of the cyclic phosphate in mediating conformational transitions from H to B forms highlighting a novel approach for rational structure-based drug design. Ideal inhibitors such as Rp-cAMPS are those that preferentially "select" inactive conformations of target proteins by satisfying all "binding" constraints alone without inducing conformational changes necessary for activation.

  3. Conformational changes in DNA-binding proteins: relationships with precomplex features and contributions to specificity and stability.

    Science.gov (United States)

    Andrabi, Munazah; Mizuguchi, Kenji; Ahmad, Shandar

    2014-05-01

    Both Proteins and DNA undergo conformational changes in order to form functional complexes and also to facilitate interactions with other molecules. These changes have direct implications for the stability and specificity of the complex, as well as the cooperativity of interactions between multiple entities. In this work, we have extensively analyzed conformational changes in DNA-binding proteins by superimposing DNA-bound and unbound pairs of protein structures in a curated database of 90 proteins. We manually examined each of these pairs, unified the authors' annotations, and summarized our observations by classifying conformational changes into six structural categories. We explored a relationship between conformational changes and functional classes, binding motifs, target specificity, biophysical features of unbound proteins, and stability of the complex. In addition, we have also investigated the degree to which the intrinsic flexibility can explain conformational changes in a subset of 52 proteins with high quality coordinate data. Our results indicate that conformational changes in DNA-binding proteins contribute significantly to both the stability of the complex and the specificity of targets recognized by them. We also conclude that most conformational changes occur in proteins interacting with specific DNA targets, even though unbound protein structures may have sufficient information to interact with DNA in a nonspecific manner. Copyright © 2013 Wiley Periodicals, Inc.

  4. The prominent conformational plasticity of lactoperoxidase: a chemical and pH stability analysis.

    Science.gov (United States)

    Boscolo, Barbara; Leal, Sónia S; Salgueiro, Carlos A; Ghibaudi, Elena M; Gomes, Cláudio M

    2009-07-01

    Lactoperoxidase (LPO) is a structurally complex and stable mammalian redox enzyme. Here we aim at evaluating the influence of ionic interactions and how these intertwine with the structural dynamics, stability and activity of LPO. In this respect, we have compared LPO guanidinium hydrochloride (GdmCl) and urea denaturation pathways and performed a detailed investigation on the effects of pH on the LPO conformational dynamics and stability. Our experimental findings using far-UV CD, Trp fluorescence emission and ESR spectroscopies clearly indicate that LPO charged-denaturation with GdmCl induced a sharp two-step process versus a three-step unfolding mechanism induced by urea. This differential effect between GdmCl and urea suggests that ionic interactions must play a rather prominent role in the stabilization of LPO. With both denaturants, the protein core was shown to retain activity up to near the respective C(m) values. Moreover, a pH titration of LPO evidenced no significant conformational alterations or perturbation of heme activity within the 4 to 11 pH interval. In contrast, alterations of ionic interactions by poising LPO at pH 3, 2 and 12 resulted in a loss of secondary structure, loosening of tertiary contacts and loss of activity, which appear to be associated with the perturbation of the hydrophobic core, as evidenced by ANS binding, as well as disruption of the heme pocket demonstrated by optical and EPR spectroscopies. Overall, LPO is characterised by a high degree of peripheral structural plasticity without perturbation of the core heme moiety. The possible physiological meaning of such features is discussed.

  5. Theory versus data: how to calculate R0?

    Directory of Open Access Journals (Sweden)

    Romulus Breban

    Full Text Available To predict the potential severity of outbreaks of infectious diseases such as SARS, HIV, TB and smallpox, a summary parameter, the basic reproduction number R(0, is generally calculated from a population-level model. R(0 specifies the average number of secondary infections caused by one infected individual during his/her entire infectious period at the start of an outbreak. R(0 is used to assess the severity of the outbreak, as well as the strength of the medical and/or behavioral interventions necessary for control. Conventionally, it is assumed that if R(0>1 the outbreak generates an epidemic, and if R(0<1 the outbreak becomes extinct. Here, we use computational and analytical methods to calculate the average number of secondary infections and to show that it does not necessarily represent an epidemic threshold parameter (as it has been generally assumed. Previously we have constructed a new type of individual-level model (ILM and linked it with a population-level model. Our ILM generates the same temporal incidence and prevalence patterns as the population-level model; we use our ILM to directly calculate the average number of secondary infections (i.e., R(0. Surprisingly, we find that this value of R(0 calculated from the ILM is very different from the epidemic threshold calculated from the population-level model. This occurs because many different individual-level processes can generate the same incidence and prevalence patterns. We show that obtaining R(0 from empirical contact tracing data collected by epidemiologists and using this R(0 as a threshold parameter for a population-level model could produce extremely misleading estimates of the infectiousness of the pathogen, the severity of an outbreak, and the strength of the medical and/or behavioral interventions necessary for control.

  6. Salt Effects on the Conformational Stability of the Visual G-Protein-Coupled Receptor Rhodopsin

    Science.gov (United States)

    Reyes-Alcaraz, Arfaxad; Martínez-Archundia, Marlet; Ramon, Eva; Garriga, Pere

    2011-01-01

    Membrane protein stability is a key parameter with important physiological and practical implications. Inorganic salts affect protein stability, but the mechanisms of their interactions with membrane proteins are not completely understood. We have undertaken the study of a prototypical G-protein-coupled receptor, the α-helical membrane protein rhodopsin from vertebrate retina, and explored the effects of inorganic salts on the thermal decay properties of both its inactive and photoactivated states. Under high salt concentrations, rhodopsin significantly increased its activation enthalpy change for thermal bleaching, whereas acid denaturation affected the formation of a denatured loose-bundle state for both the active and inactive conformations. This behavior seems to correlate with changes in protonated Schiff-base hydrolysis. However, chromophore regeneration with the 11-cis-retinal chromophore and MetarhodopsinII decay kinetics were slower only in the presence of sodium chloride, suggesting that in this case, the underlying phenomenon may be linked to the activation of rhodopsin and the retinal release processes. Furthermore, the melting temperature, determined by means of circular dichroism and differential scanning calorimetry measurements, was increased in the presence of high salt concentrations. The observed effects on rhodopsin could indicate that salts favor electrostatic interactions in the retinal binding pocket and indirectly favor hydrophobic interactions at the membrane protein receptor core. These effects can be exploited in applications where the stability of membrane proteins in solution is highly desirable. PMID:22261069

  7. An Amyloid-Like Pathological Conformation of TDP-43 Is Stabilized by Hypercooperative Hydrogen Bonds.

    Science.gov (United States)

    Mompeán, Miguel; Baralle, Marco; Buratti, Emanuele; Laurents, Douglas V

    2016-01-01

    TDP-43 is an essential RNA-binding protein forming aggregates in almost all cases of sporadic amyotrophic lateral sclerosis (ALS) and many cases of frontotemporal lobar dementia (FTLD) and other neurodegenerative diseases. TDP-43 consists of a folded N-terminal domain with a singular structure, two RRM RNA-binding domains, and a long disordered C-terminal region which plays roles in functional RNA regulatory assemblies as well as pernicious aggregation. Evidence from pathological mutations and seeding experiments strongly suggest that TDP-43 aggregates are pathologically relevant through toxic gain-of-harmful-function and/or harmful loss-of-native-function mechanisms. Recent, but not early, microscopy studies and the ability of TDP-43 aggregates to resist harsh treatment and to seed new pathological aggregates in vitro and in cells strongly suggest that TDP-43 aggregates have a self-templating, amyloid-like structure. Based on the importance of the Gln/Asn-rich 341-367 residue segment for efficient aggregation of endogenous TDP-43 when presented as a 12X-repeat and extensive spectroscopic and computational experiments, we recently proposed that this segment adopts a beta-hairpin structure that assembles in a parallel with a beta-turn configuration to form an amyloid-like structure. Here, we propose that this conformer is stabilized by an especially strong class of hypercooperative hydrogen bonding unique to Gln and Asn sidechains. The clinical existence of this conformer is supported by very recent LC-MS/MS characterization of TDP-43 from ex vivo aggregates, which show that residues 341-367 were protected in vivo from Ser phosphorylation, Gln/Asn deamidation and Met oxidation. Its distinct pattern of SDS-PAGE bands allows us to link this conformer to the exceptionally stable seed of the Type A TDP-43 proteinopathy.

  8. Investigating the Role of Conformational Effects on Laccase Stability and Hyperactivation under Stress Conditions.

    Science.gov (United States)

    Ferrario, Valerio; Chernykh, Alexey; Fiorindo, Federica; Kolomytseva, Marina; Sinigoi, Loris; Myasoedova, Nina; Fattor, Diana; Ebert, Cynthia; Golovleva, Ludmila; Gardossi, Lucia

    2015-11-02

    Fungal laccase from Steccherinum ochraceum 1833 displays remarkable stability under different harsh conditions: organic/buffer mixtures, thermal treatment, and microwave radiation. The behavior is particularly significant in the light of the sharp inactivation observed for two different fungal laccases. Laccase from S. ochraceum 1833 also displays hyperactivation under mild thermal treatment (60 °C). Molecular dynamics simulations at 80 °C explained how this laccase retains the geometry of the electron transfer pathway, thereby assuring electron transfer through the copper ions and thus maintaining its catalytic activity at high temperature. Spectroscopic studies revealed that the thermal activation corresponds to specific conformational changes in the protein. The results indicate that this laccase is potentially applicable under denaturing conditions that might be beneficial for the biotransformation of recalcitrant substrates. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Conformation and stability properties of B17: I. Analytical investigations using circular dichroism.

    Science.gov (United States)

    Khachfe, Hassan M; Atkinson, David

    2012-08-01

    Structural characterization of B17, the 17% N-terminal domain of apo B, was carried out using circular dichroic (CD) spectroscopy, where secondary and tertiary structures were studied as a function of temperature and pH. Mild acidic conditions that correlate with histidine protonation invoked a change in the α-helix and random coil contents of the protein, with no apparent change in the β-sheet structural content. Specific changes in the structure of the protein that occur in response to temperature were also investigated to understand the stability and conformational changes of B17. Far- and near-UV CDs were used to probe the thermal changes in the protein. The protonation of some histidine residues was attributed to underlie the increase in the helical content of the protein.

  10. Conformational stability analyses of alpha subunit I domain of LFA-1 and Mac-1.

    Directory of Open Access Journals (Sweden)

    Debin Mao

    Full Text Available β₂ integrin of lymphocyte function-associated antigen-1 (LFA-1 or macrophage-1 antigen (Mac-1 binds to their common ligand of intercellular adhesion molecule-1 (ICAM-1 and mediates leukocyte-endothelial cell (EC adhesions in inflammation cascade. Although the two integrins are known to have distinct functions, the corresponding micro-structural bases remain unclear. Here (steered-molecular dynamics simulations were employed to elucidate the conformational stability of α subunit I domains of LFA-1 and Mac-1 in different affinity states and relevant I domain-ICAM-1 interaction features. Compared with low affinity (LA Mac-1, the LA LFA-1 I domain was unstable in the presence or absence of ICAM-1 ligand, stemming from diverse orientations of its α₇-helix with different motifs of zipper-like hydrophobic junction between α₁- and α₇-helices. Meanwhile, spontaneous transition of LFA-1 I domain from LA state to intermediate affinity (IA state was first visualized. All the LA, IA, and high affinity (HA states of LFA-1 I domain and HA Mac-1 I domain were able to bind to ICAM-1 ligand effectively, while LA Mac-1 I domain was unfavorable for binding ligand presumably due to the specific orientation of S144 side-chain that capped the MIDAS ion. These results furthered our understanding in correlating the structural bases with their functions of LFA-1 and Mac-1 integrins from the viewpoint of I domain conformational stability and of the characteristics of I domain-ICAM-1 interactions.

  11. A Proline-Based Neuraminidase Inhibitor: DFT Studies on the Zwitterion Conformation, Stability and Formation

    Directory of Open Access Journals (Sweden)

    Zhi-Wei Yang

    2009-09-01

    Full Text Available The designs of potent neuraminidase (NA inhibitors are an efficient way to deal with the recent “2009 H1N1” influenza epidemic. In this work, density functional calculations were employed to study the conformation, stability and formation of the zwitterions of 5-[(1R,2S-1-(acetylamino-2-methoxy-2-methylpentyl]-4-[(1Z-1-propenyl]-(4S,5R-D-proline (BL, a proline-based NA inhibitor. Compared to proline, the zwitterion stability of BL is enhanced by 1.76 kcal mol-1 due to the introduction of functional groups. However, the zwitterion of BL will not represent a local minimum on the potential energy surface until the number of water molecules increases up to two (n = 2. With the addition of two and three water molecules, the energy differences between the zwitterions and corresponding canonical isomers were calculated at 3.13 and -1.54 kcal mol-1, respectively. The zwitterions of BL are mainly stabilized by the H-bonds with the water molecules, especially in the case of three water molecules where the carboxyl-O atoms are largely coordination-saturated by three H-bonds of medium strengths, causing the zwitterion stability even superior to the canonical isomer. With the presence of two and three water molecules, the energy barriers for the conversion processes from the canonical isomers to the zwitterions are equal to 4.96 and 3.13 kcal mol-1, respectively. It indicated that the zwitterion formation is facile to take place with addition of two molecules and further facilitated by more water molecules. Besides, the zwitterion formation of BL is finished in a single step, different from other NA inhibitors. Owing to the above advantages, BL is a good NA inhibitor candidate and more attention should be paid to explorations of BL-based drugs.

  12. Thermal stability of purified and reconstituted CFTR in a locked open channel conformation.

    Science.gov (United States)

    Aleksandrov, Luba A; Jensen, Timothy J; Cui, Liying; Kousouros, Joseph N; He, Lihua; Aleksandrov, Andrei A; Riordan, John R

    2015-12-01

    CFTR is unique among ABC transporters as the only one functioning as an ion channel and from a human health perspective because mutations in its gene cause cystic fibrosis. Although considerable advances have been made towards understanding CFTR's mechanism of action and the impact of mutations, the lack of a high-resolution 3D structure has hindered progress. The large multi-domain membrane glycoprotein is normally present at low copy number and when over expressed at high levels it aggregates strongly, limiting the production of stable mono-disperse preparations. While the reasons for the strong self-association are not fully understood, its relatively low thermal stability seems likely to be one. The major CF causing mutation, ΔF508, renders the protein very thermally unstable and therefore a great deal of attention has been paid to this property of CFTR. Multiple second site mutations of CFTR in NBD1 where F508 normally resides and small molecule binders of the domain increase the thermal stability of the mutant. These manipulations also stabilize the wild-type protein. Here we have applied ΔF508-stabilizing changes and other modifications to generate wild-type constructs that express at much higher levels in scaled-up suspension cultures of mammalian cells. After purification and reconstitution into liposomes these proteins are active in a locked-open conformation at temperatures as high as 50 °C and remain monodisperse at 4 °C in detergent or lipid for at least a week. The availability of adequate amounts of these and related stable active preparations of homogeneous CFTR will enable stalled structural and ligand binding studies to proceed.

  13. Investigating the conformational stability of prion strains through a kinetic replication model.

    Directory of Open Access Journals (Sweden)

    Mattia Zampieri

    2009-07-01

    Full Text Available Prion proteins are known to misfold into a range of different aggregated forms, showing different phenotypic and pathological states. Understanding strain specificities is an important problem in the field of prion disease. Little is known about which PrP(Sc structural properties and molecular mechanisms determine prion replication, disease progression and strain phenotype. The aim of this work is to investigate, through a mathematical model, how the structural stability of different aggregated forms can influence the kinetics of prion replication. The model-based results suggest that prion strains with different conformational stability undergoing in vivo replication are characterizable in primis by means of different rates of breakage. A further role seems to be played by the aggregation rate (i.e. the rate at which a prion fibril grows. The kinetic variability introduced in the model by these two parameters allows us to reproduce the different characteristic features of the various strains (e.g., fibrils' mean length and is coherent with all experimental observations concerning strain-specific behavior.

  14. Probing conformational stability and dynamics of erythroid and nonerythroid spectrin: effects of urea and guanidine hydrochloride.

    Directory of Open Access Journals (Sweden)

    Malay Patra

    Full Text Available We have studied the conformational stability of the two homologous membrane skeletal proteins, the erythroid and non-erythroid spectrins, in their dimeric and tetrameric forms respectively during unfolding in the presence of urea and guanidine hydrochloride (GuHCl. Fluorescence and circular dichroism (CD spectroscopy have been used to study the changes of intrinsic tryptophan fluorescence, anisotropy, far UV-CD and extrinsic fluorescence of bound 1-anilinonapthalene-8-sulfonic acid (ANS. Chemical unfolding of both proteins were reversible and could be described as a two state transition. The folded erythroid spectrin and non-erythroid spectrin were directly converted to unfolded monomer without formation of any intermediate. Fluorescence quenching, anisotropy, ANS binding and dynamic light scattering data suggest that in presence of low concentrations of the denaturants (up-to 1M hydrogen bonding network and van der Waals interaction play a role inducing changes in quaternary as well as tertiary structures without complete dissociation of the subunits. This is the first report of two large worm like, multi-domain proteins obeying twofold rule which is commonly found in small globular proteins. The free energy of stabilization (ΔGuH20 for the dimeric spectrin has been 20 kcal/mol lesser than the tetrameric from.

  15. Probing Conformational Stability and Dynamics of Erythroid and Nonerythroid Spectrin: Effects of Urea and Guanidine Hydrochloride

    Science.gov (United States)

    Patra, Malay; Mukhopadhyay, Chaitali; Chakrabarti, Abhijit

    2015-01-01

    We have studied the conformational stability of the two homologous membrane skeletal proteins, the erythroid and non-erythroid spectrins, in their dimeric and tetrameric forms respectively during unfolding in the presence of urea and guanidine hydrochloride (GuHCl). Fluorescence and circular dichroism (CD) spectroscopy have been used to study the changes of intrinsic tryptophan fluorescence, anisotropy, far UV-CD and extrinsic fluorescence of bound 1-anilinonapthalene-8-sulfonic acid (ANS). Chemical unfolding of both proteins were reversible and could be described as a two state transition. The folded erythroid spectrin and non-erythroid spectrin were directly converted to unfolded monomer without formation of any intermediate. Fluorescence quenching, anisotropy, ANS binding and dynamic light scattering data suggest that in presence of low concentrations of the denaturants (up-to 1M) hydrogen bonding network and van der Waals interaction play a role inducing changes in quaternary as well as tertiary structures without complete dissociation of the subunits. This is the first report of two large worm like, multi-domain proteins obeying twofold rule which is commonly found in small globular proteins. The free energy of stabilization (ΔGuH20) for the dimeric spectrin has been 20 kcal/mol lesser than the tetrameric from. PMID:25617632

  16. Fluorescence properties and conformational stability of the beta-hemocyanin of Helix pomatia.

    Science.gov (United States)

    Idakieva, Krassimira; Siddiqui, Nurul I; Parvanova, Katja; Nikolov, Peter; Gielens, Constant

    2006-04-01

    The beta-hemocyanin (beta-HpH) is one of the three dioxygen-binding proteins found freely dissolved in the hemolymph of the gastropodan mollusc Helix pomatia. The didecameric molecule (molecular mass 9 MDa) is built up of only one type of subunits. The fluorescence properties of the oxygenated and apo-form (copper-deprived) of the didecamer and its subunits were characterized. Upon excitation of the hemocyanins at 295 or 280 nm, tryptophyl residues buried in the hydrophobic interior of the protein determine the fluorescence emission. This is confirmed by quenching experiments with acrylamide, cesium chloride and potassium iodide. The copper-dioxygen system at the binuclear active site quenches the tryptophan emission of the oxy-beta-HpH. The removal of this system increases the fluorescence quantum yield and causes structural rearrangement of the microenvironment of the emitting tryptophyl residues in the apo-form. Time-resolved fluorescence measurements show that the oxygenated and copper-deprived forms of the beta-HpH and its subunits exist in different conformations. The thermal stability of the oxy- and apo-beta-HpH is characterized by a transition temperature (Tm) of 84 degrees C and 63 degrees C, respectively, obtained by differential scanning calorimetry. Increase of the temperature influences the active site at lower temperatures than the environments of tryptophans and tyrosines causing a loss of oxygen bound to the copper atoms. This process is, at least partially, reversible as after cooling of the protein samples, around 60% reinstatement of the copper-peroxide band has been observed. The results confirm the role of the copper-dioxygen complex for the stabilization of the hemocyanin structure in solution. The other important stabilizing factor is oligomerization of the hemocyanin molecule.

  17. Monomeric banana lectin at acidic pH overrules conformational stability of its native dimeric form.

    Directory of Open Access Journals (Sweden)

    Javed M Khan

    Full Text Available Banana lectin (BL is a homodimeric protein categorized among jacalin-related family of lectins. The effect of acidic pH was examined on conformational stability of BL by using circular dichroism, intrinsic fluorescence, 1-anilino-8-napthalene sulfonate (ANS binding, size exclusion chromatography (SEC and dynamic light scattering (DLS. During acid denaturation of BL, the monomerization of native dimeric protein was found at pH 2.0. The elution profile from SEC showed two different peaks (59.65 ml & 87.98 ml at pH 2.0 while single peak (61.45 ml at pH 7.4. The hydrodynamic radii (R h of native BL was 2.9 nm while at pH 2.0 two species were found with R h of 1.7 and 3.7 nm. Furthermore at, pH 2.0 the secondary structures of BL remained unaltered while tertiary structure was significantly disrupted with the exposure of hydrophobic clusters confirming the existence of molten globule like state. The unfolding of BL with different subunit status was further evaluated by urea and temperature mediated denaturation to check their stability. As inferred from high Cm and ΔG values, the monomeric form of BL offers more resistance towards chemical denaturation than the native dimeric form. Besides, dimeric BL exhibited a Tm of 77°C while no loss in secondary structures was observed in monomers even up to 95°C. To the best of our knowledge, this is the first report on monomeric subunit of lectins showing more stability against denaturants than its native dimeric state.

  18. Phospholipid Bicelles Improve the Conformational Stability of Rhodopsin Mutants Associated with Retinitis Pigmentosa.

    Science.gov (United States)

    Dong, Xiaoyun; Ramon, Eva; Herrera-Hernández, María Guadalupe; Garriga, Pere

    2015-08-11

    Mutations in the visual photoreceptor rhodopsin are the cause of the retinal degenerative disease retinitis pigmentosa. Some naturally occurring mutations can lead to protein conformational instability. Two such mutations, N55K and G90V, in the first and second transmembrane helices of the receptor, have been associated with sector and classical retinitis pigmentosa, respectively, and showed enhanced thermal sensitivity. We have carefully analyzed the effect of phospholipid bicelles on the stability and ligand binding properties of these two mutants and compared it with those of the detergent-solubilized samples. We have used a phospholipid bilayer consisting of 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine (DMPC) and 1,2-dihexanoyl-sn-glycero-3-phosphocholine (DHPC). We find that DMPC/DHPC bicelles dramatically increase the thermal stability of the rhodopsin mutants G90V and N55K. The chromophore stability and regeneration of the mutants were also increased in bicelles when compared to their behavior in a dodecyl maltoside detergent solution. The retinal release process was slowed in bicelles, and chromophore entry, after illumination, was improved for the G90V mutant but not for N55K. Furthermore, fluorescence spectroscopy measurements showed that bicelles allowed more exogenous retinal binding to the photoactivated G90V mutant than in a detergent solution. In contrast, N55K could not reposition any chromophore either in the detergent or in bicelles. The results demonstrate that DMPC/DHPC bicelles can counteract the destabilizing effect of the disease-causing mutations and can modulate the structural changes in the ensuing receptor photoactivation in a distinct specific manner for different retinitis pigmentosa mutant phenotypes.

  19. Triple-helical peptides: an approach to collagen conformation, stability, and self-association.

    Science.gov (United States)

    Brodsky, Barbara; Thiagarajan, Geetha; Madhan, Balaraman; Kar, Karunakar

    2008-05-01

    Peptides have been an integral part of the collagen triple-helix structure story, and have continued to serve as useful models for biophysical studies and for establishing biologically important sequence-structure-function relationships. High resolution structures of triple-helical peptides have confirmed the basic Ramachandran triple-helix model and provided new insights into the hydration, hydrogen bonding, and sequence dependent helical parameters in collagen. The dependence of collagen triple-helix stability on the residues in its (Gly-X-Y)(n) repeating sequence has been investigated by measuring melting temperatures of host-guest peptides and an on-line collagen stability calculator is now available. Although the presence of Gly as every third residue is essential for an undistorted structure, interruptions in the repeating (Gly-X-Y)(n) amino acid sequence pattern are found in the triple-helical domains of all nonfibrillar collagens, and are likely to play a role in collagen binding and degradation. Peptide models indicate that small interruptions can be incorporated into a rod-like triple-helix with a highly localized effect, which perturbs hydrogen bonds and places the standard triple-helices on both ends out of register. In contrast to natural interruptions, missense mutations which replace one Gly in a triple-helix domain by a larger residue have pathological consequences, and studies on peptides containing such Gly substitutions clarify their effect on conformation, stability, and folding. Recent studies suggest peptides may also be useful in defining the basic principles of collagen self-association to the supramolecular structures found in tissues.

  20. The role of PEG conformation in mixed layers: from protein corona substrate to steric stabilization avoiding protein adsorption

    Directory of Open Access Journals (Sweden)

    Joan Comenge

    2015-03-01

    Full Text Available Although nanoparticles (NPs have been traditionally modified with a single ligand layer, mixture of ligands might help to combine different functionalities and to further engineer the NP surface. A detailed study of the competition between an alkanethiol (11-mercaptoundecanoic acid and SH-PEG for the surface of AuNPs and the resultant behaviors of this model nanoconjugate is presented here. As a result, the physicochemical properties of these conjugates can be progressively tuned by controlling the composition and especially the conformation of the mixed monolayer. This has implications in the physiological stability. The controlled changes on the SH-PEG conformation rather than its concentration induce a change in the stabilization mechanism from electrostatic repulsion to steric hindrance, which changes the biological fate of NPs. Importantly, the adsorption of proteins on the conjugates can be tailored by tuning the composition and conformation of the mixed layer.

  1. Conformational stability of fibrillar amyloid-beta oligomers via protofilament pair formation - a systematic computational study.

    Science.gov (United States)

    Kahler, Anna; Sticht, Heinrich; Horn, Anselm H C

    2013-01-01

    Amyloid-[Formula: see text] (A[Formula: see text]) oligomers play a crucial role in Alzheimer's disease due to their neurotoxic aggregation properties. Fibrillar A[Formula: see text] oligomerization can lead to protofilaments and protofilament pairs via oligomer elongation and oligomer association, respectively. Small fibrillar oligomers adopt the protofilament topology, whereas fibrils contain at least protofilament pairs. To date, the underlying growth mechanism from oligomers to the mature fibril still remains to be elucidated. Here, we performed all-atom molecular dynamics simulations in explicit solvent on single layer-like protofilaments and fibril-like protofilament pairs of different size ranging from the tetramer to the 48-mer. We found that the initial U-shaped topology per monomer is maintained over time in all oligomers. The observed deviations of protofilaments from the starting structure increase significantly with size due to the twisting of the in-register parallel [Formula: see text]-sheets. This twist causes long protofilaments to be unstable and leads to a breakage. Protofilament pairs, which are stabilized by a hydrophobic interface, exhibit more fibril-like properties such as the overall structure and the twist angle. Thus, they can act as stable conformational templates for further fibril growth. Key properties like the twist angle, shape complementarity, and energetics show a size-dependent behavior so that small oligomers favor the protofilament topology, whereas large oligomers favor the protofilament pair topology. The region for this conformational transition is at the size of approximately twelve A[Formula: see text] monomers. From that, we propose the following growth mechanism from A[Formula: see text] oligomers to fibrils: (1) elongation of short protofilaments; (2) breakage of large protofilaments; (3) formation of short protofilament pairs; and (4) elongation of protofilament pairs.

  2. Conformational stability of fibrillar amyloid-beta oligomers via protofilament pair formation - a systematic computational study.

    Directory of Open Access Journals (Sweden)

    Anna Kahler

    Full Text Available Amyloid-[Formula: see text] (A[Formula: see text] oligomers play a crucial role in Alzheimer's disease due to their neurotoxic aggregation properties. Fibrillar A[Formula: see text] oligomerization can lead to protofilaments and protofilament pairs via oligomer elongation and oligomer association, respectively. Small fibrillar oligomers adopt the protofilament topology, whereas fibrils contain at least protofilament pairs. To date, the underlying growth mechanism from oligomers to the mature fibril still remains to be elucidated. Here, we performed all-atom molecular dynamics simulations in explicit solvent on single layer-like protofilaments and fibril-like protofilament pairs of different size ranging from the tetramer to the 48-mer. We found that the initial U-shaped topology per monomer is maintained over time in all oligomers. The observed deviations of protofilaments from the starting structure increase significantly with size due to the twisting of the in-register parallel [Formula: see text]-sheets. This twist causes long protofilaments to be unstable and leads to a breakage. Protofilament pairs, which are stabilized by a hydrophobic interface, exhibit more fibril-like properties such as the overall structure and the twist angle. Thus, they can act as stable conformational templates for further fibril growth. Key properties like the twist angle, shape complementarity, and energetics show a size-dependent behavior so that small oligomers favor the protofilament topology, whereas large oligomers favor the protofilament pair topology. The region for this conformational transition is at the size of approximately twelve A[Formula: see text] monomers. From that, we propose the following growth mechanism from A[Formula: see text] oligomers to fibrils: (1 elongation of short protofilaments; (2 breakage of large protofilaments; (3 formation of short protofilament pairs; and (4 elongation of protofilament pairs.

  3. Atomic view of the histidine environment stabilizing higher-pH conformations of pH-dependent proteins.

    Science.gov (United States)

    Valéry, Céline; Deville-Foillard, Stéphanie; Lefebvre, Christelle; Taberner, Nuria; Legrand, Pierre; Meneau, Florian; Meriadec, Cristelle; Delvaux, Camille; Bizien, Thomas; Kasotakis, Emmanouil; Lopez-Iglesias, Carmen; Gall, Andrew; Bressanelli, Stéphane; Le Du, Marie-Hélène; Paternostre, Maïté; Artzner, Franck

    2015-07-20

    External stimuli are powerful tools that naturally control protein assemblies and functions. For example, during viral entry and exit changes in pH are known to trigger large protein conformational changes. However, the molecular features stabilizing the higher pH structures remain unclear. Here we elucidate the conformational change of a self-assembling peptide that forms either small or large nanotubes dependent on the pH. The sub-angstrom high-pH peptide structure reveals a globular conformation stabilized through a strong histidine-serine H-bond and a tight histidine-aromatic packing. Lowering the pH induces histidine protonation, disrupts these interactions and triggers a large change to an extended β-sheet-based conformation. Re-visiting available structures of proteins with pH-dependent conformations reveals both histidine-containing aromatic pockets and histidine-serine proximity as key motifs in higher pH structures. The mechanism discovered in this study may thus be generally used by pH-dependent proteins and opens new prospects in the field of nanomaterials.

  4. The many guises of R0 (a didactic note).

    Science.gov (United States)

    Cushing, J M; Diekmann, Odo

    2016-09-01

    The basic reproduction number R0 is, by definition, the expected life time number of offspring of a newborn individual. An operationalization entails a specification of what events are considered as "reproduction" and what events are considered as "transitions from one individual-state to another". Thus, an element of choice can creep into the concretization of the definition. The aim of this note is to clearly expose this possibility by way of examples from both population dynamics and infectious disease epidemiology.

  5. Classically conformal U(1 ) ' extended standard model, electroweak vacuum stability, and LHC Run-2 bounds

    Science.gov (United States)

    Das, Arindam; Oda, Satsuki; Okada, Nobuchika; Takahashi, Dai-suke

    2016-06-01

    We consider the minimal U(1 ) ' extension of the standard model (SM) with the classically conformal invariance, where an anomaly-free U(1 ) ' gauge symmetry is introduced along with three generations of right-handed neutrinos and a U(1 ) ' Higgs field. Since the classically conformal symmetry forbids all dimensional parameters in the model, the U(1 ) ' gauge symmetry is broken by the Coleman-Weinberg mechanism, generating the mass terms of the U(1 ) ' gauge boson (Z' boson) and the right-handed neutrinos. Through a mixing quartic coupling between the U(1 ) ' Higgs field and the SM Higgs doublet field, the radiative U(1 ) ' gauge symmetry breaking also triggers the breaking of the electroweak symmetry. In this model context, we first investigate the electroweak vacuum instability problem in the SM. Employing the renormalization group equations at the two-loop level and the central values for the world average masses of the top quark (mt=173.34 GeV ) and the Higgs boson (mh=125.09 GeV ), we perform parameter scans to identify the parameter region for resolving the electroweak vacuum instability problem. Next we interpret the recent ATLAS and CMS search limits at the LHC Run-2 for the sequential Z' boson to constrain the parameter region in our model. Combining the constraints from the electroweak vacuum stability and the LHC Run-2 results, we find a bound on the Z' boson mass as mZ'≳3.5 TeV . We also calculate self-energy corrections to the SM Higgs doublet field through the heavy states, the right-handed neutrinos and the Z' boson, and find the naturalness bound as mZ'≲7 TeV , in order to reproduce the right electroweak scale for the fine-tuning level better than 10%. The resultant mass range of 3.5 TeV ≲mZ'≲7 TeV will be explored at the LHC Run-2 in the near future.

  6. Vibrational spectra, DFT calculations, conformational stabilities and assignments of the fundamentals of the 1-butylpiperazine

    Science.gov (United States)

    Bağlayan, Özge; Kaya, Mehmet Fatih; Güneş, Esma; Şenyel, Mustafa

    2016-10-01

    FT-IR and FT-Raman spectra of 1-butylpiperazine (1bpa) were experimentally recorded in the region of 4000-10 cm-1 and 4000-100 cm-1, respectively. The optimized geometric parameters, conformational equilibria, normal mode frequencies and corresponding vibrational assignments of 1bpa (C8H18N2) are theoretically examined by means of B3LYP hybrid density functional theory (DFT) method together with 6-31++G(d,p) basis set. Also, reliable conformational investigation and vibrational assignments have been performed by the potential energy surface (PES) and potential energy distribution (PED) analysis, respectively. Calculations are made for four possible conformations. According to the experimental and theoretical data, density functional B3LYP method provides reliable results for predicting vibrational wavenumbers and equatorial-equatorial conformer is considered to be the most stable form of 1bpa.

  7. R0代数中的滤子格%The Filter Lattices on R0 Algebras

    Institute of Scientific and Technical Information of China (English)

    罗清君

    2009-01-01

    In the present paper,some basic properties of MP filters of Ro algebra M are investigated.It is proved that (FMR(M),,',,,{1},M) is a bounded distributive lattice by introducing the negation operator ',the meet operator,the join operator and the implication operator on the set FMP(M) of all MP filters of M.Moreover,some conditions under which (FMP(M),,',,,{1},M) is an R0 algebra are given.And the relationship between prime elements of FMP(M) and prime filters of M is studied.Finally,some equivalent characterizations of prime elements of FMP(M) axe obtained.

  8. Microwave, infrared and Raman spectra, r0 structural parameters, ab initio calculations and vibrational assignment of 1-fluoro-1-silacyclopentane.

    Science.gov (United States)

    Durig, James R; Panikar, Savitha S; Obenchain, Daniel A; Bills, Brandon J; Lohan, Patrick M; Peebles, Rebecca A; Peebles, Sean A; Groner, Peter; Guirgis, Gamil A; Johnston, Michael D

    2012-01-28

    The microwave spectrum (6500-18 ,500 MHz) of 1-fluoro-1-silacyclopentane, c-C(4)H(8)SiHF has been recorded and 87 transitions for the (28)Si, (29)Si, (30)Si, and (13)C isotopomers have been assigned for a single conformer. Infrared spectra (3050-350 cm(-1)) of the gas and solid and Raman spectrum (3100-40 cm(-1)) of the liquid have also been recorded. The vibrational data indicate the presence of a single conformer with no symmetry which is consistent with the twist form. Ab initio calculations with a variety of basis sets up to MP2(full)/aug-cc-pVTZ predict the envelope-axial and envelope-equatorial conformers to be saddle points with nearly the same energies but much lower energy than the planar conformer. By utilizing the microwave rotational constants for seven isotopomers ((28)Si, (29)Si, (30)Si, and four (13)C) combined with the structural parameters predicted from the MP2(full)/6-311+G(d,p) calculations, adjusted r(0) structural parameters have been obtained for the twist conformer. The heavy atom distances in Å are: r(0)(SiC(2)) = 1.875(3); r(0)(SiC(3)) = 1.872(3); r(0)(C(2)C(4)) = 1.549(3); r(0)(C(3)C(5)) = 1.547(3); r(0)(C(4)C(5)) = 1.542(3); r(0)(SiF) = 1.598(3) and the angles in degrees are: [angle]CSiC = 96.7(5); [angle]SiC(2)C(4) = 103.6(5); [angle]SiC(3)C(5) = 102.9(5); [angle]C(2)C(4)C(5) = 108.4(5); [angle]C(3)C(5)C(4) = 108.1(5); [angle]F(6)Si(1)C(2) = 110.7(5); [angle]F(6)Si(1)C(3) = 111.6(5). The heavy atom ring parameters are compared to the corresponding r(s) parameters. Normal coordinate calculations with scaled force constants from MP2(full)/6-31G(d) calculations were carried out to predict the fundamental vibrational frequencies, infrared intensities, Raman activities, depolarization values, and infrared band contours. These experimental and theoretical results are compared to the corresponding quantities of some other five-membered rings.

  9. On the conformational stability of the smallest RNA kissing complexes maintained through two G·C base pairs.

    Science.gov (United States)

    Chu, Wally; Weerasekera, Akila; Kim, Chul-Hyun

    2017-01-29

    Two identical 5'GACG3' tetra-loop motifs with different stem sequences (called H2 and H3) are found in the 5' end region of Moloney Murine Leukemia Virus (MMLV) genomic RNA. They play important roles in RNA dimerization and encapsidation through two identical tetra-loops (5'GACG3') forming a loop-to-loop kissing complex, the smallest RNA kissing complex ever found in nature. We examined the effects of a loop-closing base pair as well as a stem sequence on the conformational stability of the kissing complex. UV melting analysis and gel electrophoresis were performed on eight RNA sequences mimicking the H2 and H3 hairpin tetra-loops with variation in loop-closing base pairs. Our results show that changing the loop-closing base pair from the wildtype (5'A·U3' for H3, 5'U·A3' for H2) to 5'G·C3'/5'C·G3' has significant effect on the stability of the kissing complexes: the substitution to 5'C·G3' significantly decreases both thermal and mechanical stability, while switching to the 5'G·C3' significantly increases the mechanical stability only. The kissing complexes with the wildtype loop-closing base pairs (5'A·U3' for H3 and 5'U·A3' for H2) show different stability when attached to a different stem sequence (H2 stem vs. H3 stem). This suggests that not only the loop-closing base pair itself, but also the stem sequence, affects the conformational stability of the RNA kissing complex. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Influence of Tableting on the Conformation and Thermal Stability of Trypsin as a Model Protein

    DEFF Research Database (Denmark)

    Klukkert, Marten; Van De Weert, Marco; Fanø, Mathias

    2015-01-01

    conformation and the extent of their reversibility were determined using solid- and liquid-state IR spectroscopy together with principal component analysis and an area overlap approach. Trypsin enzymatic activity was determined by a photometric assay. Liquid-state differential scanning calorimetry......The objective of this study was to investigate the influence of compaction on the conformation of trypsin, its transition temperature (Tm ) of unfolding, and its folding reversibility after thermal denaturation. Plain trypsin was compacted at 40-382 MPa. Pressure-induced changes in the trypsin...... was performed to determine the Tm as well as the folding reversibility after thermal denaturation of the reconstituted samples. It was found that compacted samples showed reduced activity accompanied by an altered secondary structure. Conformational changes that occur in the solid state were partially...

  11. Microwave, r{sub 0} structural parameters, conformational stability and vibrational assignment of cyclopropylcyanosilane

    Energy Technology Data Exchange (ETDEWEB)

    Durig, James R., E-mail: durigj@umkc.edu [Department of Chemistry, University of Missouri-Kansas City, Kansas City, MO 64110 (United States); Guirgis, Gamil A. [Department of Chemistry and Biochemistry, College of Charleston, Charleston, SC 29424 (United States); Sawant, Dattatray K. [Department of Chemistry, University of Missouri-Kansas City, Kansas City, MO 64110 (United States); Seifert, Nathan A. [Department of Chemistry , University of Virginia, Charlottesville, VA 22904 (United States); Deodhar, Bhushan S. [Department of Chemistry, University of Missouri-Kansas City, Kansas City, MO 64110 (United States); Pate, Brooks H. [Department of Chemistry , University of Virginia, Charlottesville, VA 22904 (United States); Panikar, Savitha S.; Groner, Peter [Department of Chemistry, University of Missouri-Kansas City, Kansas City, MO 64110 (United States); Overby, Jason S.; Askarian, Sahand M. [Department of Chemistry and Biochemistry, College of Charleston, Charleston, SC 29424 (United States)

    2014-12-05

    Highlights: • The most stable cis conformer has been identified from microwave spectra. • Enthalpy difference has been determined between the two forms. • Adjusted r{sub 0} structures were obtained for cis and gauche form. • Ab initio calculations were performed for the two conformers. - Abstract: The FT-microwave spectrum (6000–19,800 MHz) of cyclopropylcyanosilane, c-C{sub 3}H{sub 5}SiH{sub 2}CN has been recorded and 773 transitions for the {sup 28}Si, {sup 29}Si, {sup 30}Si, {sup 13}C and {sup 15}N isotopomers have been assigned for cis and gauche conformers. Infrared spectra (3200–220 cm{sup −1}) of gas and Raman spectra (3200–40 cm{sup −1}) of the liquid have been recorded as well as the variable temperature (−60 to −100 °C) studies of the infrared spectra of the sample dissolved in liquid xenon. The enthalpy difference between the conformers in xenon solutions has been determined to be 123 ± 13 cm{sup −1} (1.47 ± 0.16 kJ mol{sup −1}) with the cis conformer as the more stable form. Approximately 48 ± 2% of the cis form is present at ambient temperature. By utilizing the microwave rotational constants of six isotopomers for cis and seven isotopomers for gauche combined with the structural parameters predicted from MP2(full)/6-311+G(d,p) calculations, adjusted r{sub 0} parameters have been obtained for both conformers.

  12. Stabilizing effects of G protein on the active conformation of adenosine A1 receptor differ depending on G protein type.

    Science.gov (United States)

    Tateyama, Michihiro; Kubo, Yoshihiro

    2016-10-05

    G protein coupled receptors (GPCRs) trigger various cellular and physiological responses upon the ligand binding. The ligand binding induces conformational change in GPCRs which allows G protein to interact with the receptor. The interaction of G protein also affects the active conformation of GPCRs. In this study, we have investigated the effects of Gαi1, Gαo and chimeric Gαqi5 on the active conformation of the adenosine A1 receptor, as each Gα showed difference in the interaction with adenosine A1 receptor. The conformational changes in the adenosine A1 receptor were detected as the agonist-induced decreases in efficiency of Förster resonance energy transfer (FRET) between fluorescent proteins (FPs) fused at the two intracellular domains of the adenosine A1 receptor. Amplitudes of the agonist-induced FRET decreases were subtle when the FP-tagged adenosine A1 receptor was expressed alone, whereas they were significantly enhanced when co-expressed with Gαi1Gβ1Gγ22 (Gi1) or Gαqi5Gβ1Gγ22 (Gqi5) but not with GαοGβ1Gγ22 (Go). The enhancement of the agonist-induced FRET decrease in the presence of Gqi5 was significantly larger than that of Gi1. Furthermore, the FRET recovery upon the agonist removal in the presence of Gqi5 was significantly slower than that of Gi1. From these results it was revealed that the agonist-bound active conformation of adenosine A1 receptor is unstable without the binding of G protein and that the stabilizing effects of G protein differ depending on the types of G protein.

  13. Exploring the conformational space of chromatin fibers and their stability by numerical dynamic phase diagrams.

    Science.gov (United States)

    Stehr, René; Schöpflin, Robert; Ettig, Ramona; Kepper, Nick; Rippe, Karsten; Wedemann, Gero

    2010-03-17

    The three-dimensional structure of chromatin affects DNA accessibility and is therefore a key regulator of gene expression. However, the path of the DNA between consecutive nucleosomes, and the resulting chromatin fiber organization remain controversial. The conformational space available for the folding of the nucleosome chain has been analytically described by phase diagrams with a two-angle model, which describes the chain trajectory by a DNA entry-exit angle at the nucleosome and a torsion angle between consecutive nucleosomes. Here, a novel type of numerical phase diagrams is introduced that relates the geometric phase space to the energy associated with a given chromatin conformation. The resulting phase diagrams revealed differences in the energy landscape that reflect the probability of a given conformation to form in thermal equilibrium. Furthermore, we investigated the effects of entropy and additional degrees of freedom in the dynamic phase diagrams by performing Monte Carlo simulations of the initial chain trajectories. Using our approach, we were able to demonstrate that conformations that initially were geometrically impossible could evolve into energetically favorable states in thermal equilibrium due to DNA bending and torsion. In addition, dynamic phase diagrams were applied to identify chromatin fibers that reflect certain experimentally determined features.

  14. The conformational stability and biophysical properties of the eukaryotic thioredoxins of Pisum sativum are not family-conserved.

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    David Aguado-Llera

    Full Text Available Thioredoxins (TRXs are ubiquitous proteins involved in redox processes. About forty genes encode TRX or TRX-related proteins in plants, grouped in different families according to their subcellular localization. For instance, the h-type TRXs are located in cytoplasm or mitochondria, whereas f-type TRXs have a plastidial origin, although both types of proteins have an eukaryotic origin as opposed to other TRXs. Herein, we study the conformational and the biophysical features of TRXh1, TRXh2 and TRXf from Pisum sativum. The modelled structures of the three proteins show the well-known TRX fold. While sharing similar pH-denaturations features, the chemical and thermal stabilities are different, being PsTRXh1 (Pisum sativum thioredoxin h1 the most stable isoform; moreover, the three proteins follow a three-state denaturation model, during the chemical-denaturations. These differences in the thermal- and chemical-denaturations result from changes, in a broad sense, of the several ASAs (accessible surface areas of the proteins. Thus, although a strong relationship can be found between the primary amino acid sequence and the structure among TRXs, that between the residue sequence and the conformational stability and biophysical properties is not. We discuss how these differences in the biophysical properties of TRXs determine their unique functions in pea, and we show how residues involved in the biophysical features described (pH-titrations, dimerizations and chemical-denaturations belong to regions involved in interaction with other proteins. Our results suggest that the sequence demands of protein-protein function are relatively rigid, with different protein-binding pockets (some in common for each of the three proteins, but the demands of structure and conformational stability per se (as long as there is a maintained core, are less so.

  15. Lid opening and conformational stability of T1 Lipase is mediated by increasing chain length polar solvents

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    Jonathan Maiangwa

    2017-05-01

    Full Text Available The dynamics and conformational landscape of proteins in organic solvents are events of potential interest in nonaqueous process catalysis. Conformational changes, folding transitions, and stability often correspond to structural rearrangements that alter contacts between solvent molecules and amino acid residues. However, in nonaqueous enzymology, organic solvents limit stability and further application of proteins. In the present study, molecular dynamics (MD of a thermostable Geobacillus zalihae T1 lipase was performed in different chain length polar organic solvents (methanol, ethanol, propanol, butanol, and pentanol and water mixture systems to a concentration of 50%. On the basis of the MD results, the structural deviations of the backbone atoms elucidated the dynamic effects of water/organic solvent mixtures on the equilibrium state of the protein simulations in decreasing solvent polarity. The results show that the solvent mixture gives rise to deviations in enzyme structure from the native one simulated in water. The drop in the flexibility in H2O, MtOH, EtOH and PrOH simulation mixtures shows that greater motions of residues were influenced in BtOH and PtOH simulation mixtures. Comparing the root mean square fluctuations value with the accessible solvent area (SASA for every residue showed an almost correspondingly high SASA value of residues to high flexibility and low SASA value to low flexibility. The study further revealed that the organic solvents influenced the formation of more hydrogen bonds in MtOH, EtOH and PrOH and thus, it is assumed that increased intraprotein hydrogen bonding is ultimately correlated to the stability of the protein. However, the solvent accessibility analysis showed that in all solvent systems, hydrophobic residues were exposed and polar residues tended to be buried away from the solvent. Distance variation of the tetrahedral intermediate packing of the active pocket was not conserved in organic solvent

  16. The body-centered cubic structure of methyllithium tetramer crystal: staggered methyl conformation by electrostatic stabilization via intratetramer multipolarization.

    Science.gov (United States)

    Ohta, Yusuke; Demura, Akimitsu; Okamoto, Takuya; Hitomi, Haruko; Nagaoka, Masataka

    2006-06-29

    The methyllithium tetramer (CH3Li)4 structure in the bcc crystal has been theoretically optimized with the use of density functional theory calculations under the periodic boundary condition. The X-ray structure shows that the methyl-group conformation in tetramer in crystal takes the staggered form rather than the eclipsed form that is taken in the isolated tetramer, i.e., the crystal packing effect, and this has been reproduced for the first time. It is concluded that the staggered form is advantageous in crystal, as a whole, due to the larger electrostatic stabilization via the induced intratetramer multipolarization, although it should cause, simultaneously, smaller destabilization in intratetramer electronic energy.

  17. The presence of the iron-sulfur motif is important for the conformational stability of the antiviral protein, Viperin.

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    Shubhasis Haldar

    Full Text Available Viperin, an antiviral protein, has been shown to contain a CX(3CX(2C motif, which is conserved in the radical S-adenosyl-methionine (SAM enzyme family. A triple mutant which replaces these three cysteines with alanines has been shown to have severe deficiency in antiviral activity. Since the crystal structure of Viperin is not available, we have used a combination of computational methods including multi-template homology modeling and molecular dynamics simulation to develop a low-resolution predicted structure. The results show that Viperin is an α-β protein containing iron-sulfur cluster at the center pocket. The calculations suggest that the removal of iron-sulfur cluster would lead to collapse of the protein tertiary structure. To verify these predictions, we have prepared, expressed and purified four mutant proteins. In three mutants individual cysteine residues were replaced by alanine residues while in the fourth all the cysteines were replaced by alanines. Conformational analyses using circular dichroism and steady state fluorescence spectroscopy indicate that the mutant proteins are partially unfolded, conformationally unstable and aggregation prone. The lack of conformational stability of the mutant proteins may have direct relevance to the absence of their antiviral activity.

  18. Conformation stability, halogen and solvent effects on CO stretching of 4-chloro-3-halogenobenzaldehydes.

    Science.gov (United States)

    Tursun, Mahir; Parlak, Cemal

    2015-04-15

    The effects of halogen and solvent on the conformation and carbonyl stretching of 4-chloro-3-halogenobenzaldehydes [C7H4ClXO; X=F (CFB), Cl (CCB) or Br (CBB)] were investigated using the density functional theory (DFT) method. The B3LYP functional was used by the 6-311+G(3df,p) basis set in combination with the polarizable continuum model (PCM). Computations were focused on the cis and trans isomers of the compounds in 18 different polar or non-polar organic solvents. The theoretical frequencies of the solvent-induced CO stretching vibrations were correlated with the empirical solvent parameters such as the Kirkwood-Bauer-Magat (KBM) equation, the solvent acceptor number (AN), Swain parameters and the linear solvation energy relationships (LSER). The present work explores the effect of both the halogen and medium on the conformational preference and CO vibrational frequency. The findings of this work can be useful to those systems involving changes in the conformations analogous to the compounds studied.

  19. Electroweak vacuum stability in classically conformal $B-L$ extension of the Standard Model

    CERN Document Server

    Das, Arindam; Papapietro, Nathan

    2015-01-01

    We consider the minimal U(1)$_{B-L}$ extension of the Standard Model (SM) with the classically conformal invariance, where an anomaly free U(1)$_{B-L}$ gauge symmetry is introduced along with three generations of right-handed neutrinos and a U(1)$_{B-L}$ Higgs field. Because of the classically conformal symmetry, all dimensional parameters are forbidden. The $B-L$ gauge symmetry is radiatively broken through the Coleman-Weinberg mechanism, generating the mass for the $U(1)_{B-L}$ gauge boson ($Z^\\prime$ boson) and the right-handed neutrinos. Through a small negative coupling between the SM Higgs doublet and the $B-L$ Higgs field, the negative mass term for the SM Higgs doublet is generated and the electroweak symmetry is broken. In this model context, we investigate the electroweak vacuum instability problem in the SM. It is known that in the classically conformal U(1)$_{B-L}$ extension of the SM, the electroweak vacuum remains unstable in the renormalization group analysis at the one-loop level. In this pape...

  20. Pluronic F68 enhanced the conformational stability of salmon calcitonin in both aqueous solution and lyophilized solid form.

    Science.gov (United States)

    Lee, Ting-Huei; Lin, Shan-Yang

    2011-11-01

    The effects of different surfactants on the conformational stability and structural similarity of salmon calcitonin (sCT) in aqueous solution and lyophilized forms were investigated by using microscopic Fourier transform infrared (FTIR) spectroscopy with second-derivative spectral analysis. Six surfactants, HCO-60, sodium dodecyl sulfate (SDS), Tween 80, PEG 400, Pluronic 68, and F127 were selected. The sCT aqueous solution with or without different surfactants was, respectively, incubated at 40°C for up to 35 h. sCT films were casted on the CaF(2) plates and IR spectra were collected as a function of incubation time. Second derivative analysis showed that the native sCT having a major α-helical structure was gradually changed to the combination of α-helix, random coil, and β-sheet conformations in aqueous solution at 40°C. Similar conformational changes with delayed β-sheet formation were obtained for sCT after co-incubation with all the surfactants except Pluronic F68. When the native sCT was freeze-dried alone, a marked conformational alteration was found as illustrated by a poor spectral correlation coefficient (r) value of 0.823 as compared to that of the unlyophilized native sCT. This r value was significantly deviated from 1, strongly indicating the influence of lyophilization stress on the surfactant-free sCT. The r value for sCT after lyophilizing with HCO-60, Pluronic F127, PEG 400, or Pluronic F68 was >0.9, suggesting the possible stabilization of these surfactants in the lyophilization process. The sCT sample after lyophilizing with Pluronic F68 showed a highest r value (>0.968), indicating the most optimal stabilization effect of Pluronic F68 for sCT sample via lyophilization. Pluronic F68 was found to be the preferential surfactant for preventing the secondary structure changes in aqueous solution at 40°C as well as in lyophilized powder.

  1. New insights into rotavirus entry machinery: stabilization of rotavirus spike conformation is independent of trypsin cleavage.

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    Javier M Rodríguez

    2014-05-01

    Full Text Available The infectivity of rotavirus, the main causative agent of childhood diarrhea, is dependent on activation of the extracellular viral particles by trypsin-like proteases in the host intestinal lumen. This step entails proteolytic cleavage of the VP4 spike protein into its mature products, VP8* and VP5*. Previous cryo-electron microscopy (cryo-EM analysis of trypsin-activated particles showed well-resolved spikes, although no density was identified for the spikes in uncleaved particles; these data suggested that trypsin activation triggers important conformational changes that give rise to the rigid, entry-competent spike. The nature of these structural changes is not well understood, due to lack of data relative to the uncleaved spike structure. Here we used cryo-EM and cryo-electron tomography (cryo-ET to characterize the structure of the uncleaved virion in two model rotavirus strains. Cryo-EM three-dimensional reconstruction of uncleaved virions showed spikes with a structure compatible with the atomic model of the cleaved spike, and indistinguishable from that of digested particles. Cryo-ET and subvolume average, combined with classification methods, resolved the presence of non-icosahedral structures, providing a model for the complete structure of the uncleaved spike. Despite the similar rigid structure observed for uncleaved and cleaved particles, trypsin activation is necessary for successful infection. These observations suggest that the spike precursor protein must be proteolytically processed, not to achieve a rigid conformation, but to allow the conformational changes that drive virus entry.

  2. Classically conformal U(1)' extended standard model, electroweak vacuum stability, and LHC Run-2 bounds

    CERN Document Server

    Das, Arindam; Okada, Nobuchika; Takahashi, Dai-suke

    2016-01-01

    We consider the minimal U(1)' extension of the Standard Model (SM) with the classically conformal invariance, where an anomaly free U(1)' gauge symmetry is introduced along with three generations of right-handed neutrinos and a U(1)' Higgs field. Since the classically conformal symmetry forbids all dimensional parameters in the model, the U(1)' gauge symmetry is broken through the Coleman-Weinberg mechanism, generating the mass terms of the U(1)' gauge boson (Z' boson) and the right-handed neutrinos. Through a mixing quartic coupling between the U(1)' Higgs field and the SM Higgs doublet field, the radiative U(1)' gauge symmetry breaking also triggers the breaking of the electroweak symmetry. In this model context, we first investigate the electroweak vacuum instability problem in the SM. Employing the renormalization group equations at the two-loop level and the central values for the world average masses of the top quark ($m_t=173.34$ GeV) and the Higgs boson ($m_h=125.09$ GeV), we perform parameter scans t...

  3. Studies of the conformational stability of invasion plasmid antigen B from Shigella.

    Science.gov (United States)

    Choudhari, Shyamal P; Kramer, Ryan; Barta, Michael L; Greenwood, Jamie C; Geisbrecht, Brian V; Joshi, Sangeeta B; Picking, William D; Middaugh, C Russell; Picking, Wendy L

    2013-05-01

    Shigella spp. are the causative agent of shigellosis, the second leading cause of diarrhea in children of ages 2-5. Despite many years of research, a protective vaccine has been elusive. We recently demonstrated that invasion plasmid antigens B and D (IpaB and IpaD) provide protection against S. flexneri and S. sonnei. These proteins, however, have very different properties which must be recognized and then managed during vaccine formulation. Herein, we employ spectroscopy to assess the stability of IpaB as well as IpgC (invasion protein gene), IpaB's cognate chaperone, and the IpaB/IpgC complex. The resulting data are mathematically summarized into a visual map illustrating the stability of the proteins and their complex as a function of pH and temperature. The IpaB/IpgC complex exhibits thermal stability at higher pH values but, though initially stable, quickly unfolds with increasing temperature when maintained at lower pH. In contrast, IpaB is a much more complex protein exhibiting increased stability at higher pH, but shows initial instability at lower pH values with pH 5 showing a distinct transition. IpgC precipitates at and below pH 5 and is stable above pH 7. Most strikingly, it is clear that complex formation results in stabilization of the two components. This work serves as a basis for the further development of IpaB as a vaccine candidate as well as extends our understanding of the structural stability of the Shigella type III secretion system.

  4. Far infrared and low frequency gas phase Raman spectra and conformational stability of the 1-halopropanes

    Science.gov (United States)

    Durig, J. R.; Godbey, S. E.; Sullivan, J. F.

    1984-06-01

    The far infrared (375-50 cm-1) and low frequency Raman (400-70 cm-1) spectra of the gaseous 1-halopropanes CH3CH2CH2F, CH3CH2CH2Cl, and CH3CH2CH2Br have been recorded and both the methyl and asymmetric torsional modes have been observed and assigned for both the gauche and trans conformers for all of these molecules. The asymmetric torsions for each molecule have several observed excited states which fall on the low frequency side of the fundamental. The asymmetric torsional potential functions have been calculated and, from these potential functions, the enthalpy differences between the high energy trans and low energy gauche conformers have been determined to be 122±10 cm-1 for the fluoride, 127±10 cm-1 for the chloride, and 37±10 cm-1 for the bromide. The trans and gauche methyl torsions have also been observed and assigned for the three 1-halopropanes. The resulting barriers in cm-1 are: 936±4 (trans), 986±9 (gauche) for 1-fluoropropane; 929±2 (trans), 1080±3 (gauche) for 1-chloropropane; and 841 (trans), 1016±8 (gauche) for 1-bromopropane. A complete vibrational assignment has also been made for the 1-fluoropropane molecule and, from the spectral data for the solid, it appears that there are two or more molecules per primitive cell. Attempts to obtain experimental values for the enthalpy differences in the gas phase were made and these results, as well as the determined potential functions, are discussed in relation to previous studies.

  5. Complete conformational stability of kinetically stable dimeric serine protease milin against pH, temperature, urea, and proteolysis.

    Science.gov (United States)

    Yadav, Subhash Chandra; Jagannadham, Medicherla V

    2009-09-01

    Spectroscopic, calorimetric, and proteolytic methods were utilized to evaluate the stability of the kinetically stable, differentially glycosylated, dimeric serine protease milin as a function of pH (1.0-11.0), temperature, urea, and GuHCl denaturation in presence of 8 M urea at pH 2.0. The stability of milin remains equivalent to that of native at pH 1.0-11.0. However, negligible and reversible alteration in structure upon temperature transition has been observed at pH 2.0 and with 1.6 M GuHCl. Irreversible and incomplete calorimetric transition with apparent T (m) > 100 degrees C was observed at basic pH (9.0 and 10.0). Urea-induced unfolding at pH 4.0, and at pH 2.0 with GuHCl, in presence of 8 M urea also reveals incomplete unfolding. Milin has been found to exhibit proteolytic resistant in either native or denatured state against various commercial proteases. These results imply that the high conformational stability of milin against various denaturating conditions enable its potential use in protease-based industries.

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

    Science.gov (United States)

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

    2015-03-27

    The urokinase-type plasminogen activator receptor (uPAR) is a multidomain glycolipid-anchored membrane protein, which facilitates extracellular matrix remodeling by focalizing plasminogen activation to cell surfaces via its high-affinity interaction with uPA. The modular assembly of its three LU (Ly6/uPAR-like) domains is inherently flexible and binding of uPA drives uPAR into its closed conformation, which presents the higher-affinity state for vitronectin thus providing an allosteric regulatory mechanism. Using a new class of epitope-mapped anti-uPAR monoclonal antibodies (mAbs), we now demonstrate that the reciprocal stabilization is indeed also possible. By surface plasmon resonance studies, we show that these mAbs and vitronectin have overlapping binding sites on uPAR and that they share Arg91 as hotspot residue in their binding interfaces. The crystal structure solved for one of these uPAR·mAb complexes at 3.0Å clearly shows that this mAb preselects the closed uPAR conformation with an empty but correctly assembled large hydrophobic binding cavity for uPA. Accordingly, these mAbs inhibit the uPAR-dependent lamellipodia formation and migration on vitronectin-coated matrices irrespective of the conformational status of uPAR and its occupancy with uPA. This is the first study to the best of our knowledge, showing that the dynamic assembly of the three LU domains in uPARwt can be driven toward the closed form by an external ligand, which is not engaging the hydrophobic uPA binding cavity. As this binding interface is also exploited by the somatomedin B domain of vitronectin, therefore, this relationship should be taken into consideration when exploring uPAR-dependent cell adhesion and migration in vitronectin-rich environments. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Intramolecular interactions stabilizing compact conformations of the intrinsically disordered kinase-inhibitor domain of Sic1: a molecular dynamics investigation.

    Directory of Open Access Journals (Sweden)

    Matteo eLambrughi

    2012-11-01

    Full Text Available Cyclin-dependent kinase inhibitors (CKIs are key regulatory proteins of the eukaryotic cell cycle, which modulate cyclin-dependent kinase (Cdk activity. CKIs perform their inhibitory effect by the formation of ternary complexes with a target kinase and its cognate cyclin. These regulators generally belong to the class of intrinsically disordered proteins (IDPs, which lack a well-defined and organized three-dimensional structure in their free state, undergoing folding upon binding to specific partners. Unbound IDPs are not merely random-coil structures, but can present intrinsically folded structural units (IFSUs and collapsed conformations. These structural features can be relevant to protein function in vivo.The yeast CKI Sic1 is a 284-amino acid IDP that binds to Cdk1 in complex with the Clb5,6 cyclins, preventing phosphorylation of G1 substrates and, therefore, entrance to the S phase. Sic1 degradation, triggered by multiple phosphorylation events, promotes cell-cycle progression. Previous experimental studies pointed out a propensity of Sic1 and its isolated domains to populate both extended and compact conformations. The present contribution provides models of the compact conformations of the Sic1 kinase-inhibitory domain (KID by all-atom molecular-dynamics simulations in explicit solvent and in the absence of interactors. The results are integrated by spectroscopic and spectrometric data. Helical IFSUs are identified, along with networks of intramolecular interactions. The results identify a group of hub residues and electrostatic interactions which are likely to be involved in the stabilization of globular states.

  8. Study of conformational stability, structural, electronic and charge transfer properties of cladrin using vibrational spectroscopy and DFT calculations.

    Science.gov (United States)

    Singh, Swapnil; Singh, Harshita; Srivastava, Anubha; Tandon, Poonam; Sinha, Kirti; Bharti, Purnima; Kumar, Sudhir; Kumar, Padam; Maurya, Rakesh

    2014-11-11

    In the present work, a detailed conformational study of cladrin (3-(3,4-dimethoxy phenyl)-7-hydroxychromen-4-one) has been done by using spectroscopic techniques (FT-IR/FT-Raman/UV-Vis/NMR) and quantum chemical calculations. The optimized geometry, wavenumber and intensity of the vibrational bands of the cladrin in ground state were calculated by density functional theory (DFT) employing 6-311++G(d,p) basis sets. The study has been focused on the two most stable conformers that are selected after the full geometry optimization of the molecule. A detailed assignment of the FT-IR and FT-Raman spectra has been done for both the conformers along with potential energy distribution for each vibrational mode. The observed and scaled wavenumber of most of the bands has been found to be in good agreement. The UV-Vis spectrum has been recorded and compared with calculated spectrum. In addition, 1H and 13C nuclear magnetic resonance spectra have been also recorded and compared with the calculated data that shows the inter or intramolecular hydrogen bonding. The electronic properties such as HOMO-LUMO energies were calculated by using time-dependent density functional theory. Molecular electrostatic potential has been plotted to elucidate the reactive part of the molecule. Natural bond orbital analysis was performed to investigate the molecular stability. Non linear optical property of the molecule have been studied by calculating the electric dipole moment (μ) and the first hyperpolarizability (β) that results in the nonlinearity of the molecule.

  9. The role of weakly polar and H-bonding interactions in the stabilization of the conformers of FGG, WGG, and YGG: an aqueous phase computational study.

    Science.gov (United States)

    Csontos, József; Murphy, Richard F; Lovas, Sándor

    2008-11-01

    The energetics of intramolecular interactions on the conformational potential energy surface of the terminally protected N-Ac-Phe-Gly-Gly-NHMe (FGG), N-Ac-Trp-Gly-Gly-NHMe (WGG), and N-Ac-Tyr-Gly-Gly-NHMe (YGG) tripeptides was investigated. To identify the representative conformations, simulated annealing molecular dynamics (MD) and density functional theory (DFT) methods were used. The interaction energies were calculated at the BHandHLYP/aug-cc-pVTZ level of theory. In the global minima, 10%, 31%, and 10% of the stabilization energy come from weakly polar interactions, respectively, in FGG, WGG, and YGG. In the prominent cases 46%, 62%, and 46% of the stabilization energy is from the weakly polar interactions, respectively, in FGG, WGG, and YGG. On average, weakly polar interactions account for 15%, 34%, and 9% of the stabilization energies of the FGG, WGG, and YGG conformers, respectively. Thus, weakly polar interactions can make an important energetic contribution to protein structure and function.

  10. Correctors of ΔF508 CFTR restore global conformational maturation without thermally stabilizing the mutant protein.

    Science.gov (United States)

    He, Lihua; Kota, Pradeep; Aleksandrov, Andrei A; Cui, Liying; Jensen, Tim; Dokholyan, Nikolay V; Riordan, John R

    2013-02-01

    Most cystic fibrosis is caused by the deletion of a single amino acid (F508) from CFTR and the resulting misfolding and destabilization of the protein. Compounds identified by high-throughput screening to improve ΔF508 CFTR maturation have already entered clinical trials, and it is important to understand their mechanisms of action to further improve their efficacy. Here, we showed that several of these compounds, including the investigational drug VX-809, caused a much greater increase (5- to 10-fold) in maturation at 27 than at 37°C (CFTR can be completely assembled and evade cellular quality control systems, while remaining thermodynamically unstable. He, L., Kota, P., Aleksandrov, A. A., Cui, L., Jensen, T., Dokholyan, N. V., Riordan, J. R. Correctors of ΔF508 CFTR restore global conformational maturation without thermally stabilizing the mutant protein.

  11. The two C-terminal tyrosines stabilize occluded Na/K pump conformations containing Na or K ions.

    Science.gov (United States)

    Vedovato, Natascia; Gadsby, David C

    2010-07-01

    Interactions of the three transported Na ions with the Na/K pump remain incompletely understood. Na/K pump crystal structures show that the extended C terminus of the Na,K-adenosine triphosphatase (ATPase) alpha subunit directly contacts transmembrane helices. Deletion of the last five residues (KETYY in almost all Na/K pumps) markedly lowered the apparent affinity for Na activation of pump phosphorylation from ATP, a reflection of cytoplasmic Na affinity for forming the occluded E1P(Na3) conformation. ATPase assays further suggested that C-terminal truncations also interfere with low affinity Na interactions, which are attributable to extracellular effects. Because extracellular Na ions traverse part of the membrane's electric field to reach their binding sites in the Na/K pump, their movements generate currents that can be monitored with high resolution. We report here electrical measurements to examine how Na/K pump interactions with extracellular Na ions are influenced by C-terminal truncations. We deleted the last two (YY) or five (KESYY) residues in Xenopus laevis alpha1 Na/K pumps made ouabain resistant by either of two kinds of point mutations and measured their currents as 10-mM ouabain-sensitive currents in Xenopus oocytes after silencing endogenous Xenopus Na/K pumps with 1 microM ouabain. We found the low affinity inhibitory influence of extracellular Na on outward Na/K pump current at negative voltages to be impaired in all of the C-terminally truncated pumps. Correspondingly, voltage jump-induced transient charge movements that reflect pump interactions with extracellular Na ions were strongly shifted to more negative potentials; this signals a several-fold reduction of the apparent affinity for extracellular Na in the truncated pumps. Parallel lowering of Na affinity on both sides of the membrane argues that the C-terminal contacts provide important stabilization of the occluded E1P(Na3) conformation, regardless of the route of Na ion entry into the

  12. 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.

  13. Classically conformal U(1)$^\\prime$ extended Standard Model and Higgs vacuum stability

    CERN Document Server

    Oda, Satsuki; Takahashi, Dai-suke

    2015-01-01

    We consider the minimal U(1)$^\\prime$ extension of the Standard Model (SM) with conformal invariance at the classical level, where in addition to the SM particle contents, three generations of right-handed neutrinos and a U(1)$^\\prime$ Higgs field are introduced. In the presence of the three right-handed neutrinos, which are responsible for the seesaw mechanism, this model is free from all the gauge and gravitational anomalies. The U(1)$^\\prime$ gauge symmetry is radiatively broken via the Coleman-Weinberg mechanism, by which the U(1)$^\\prime$ gauge boson ($Z^\\prime$ boson) mass as well as the Majorana mass for the right-handed neutrinos are generated. The radiative U(1)$^\\prime$ symmetry breaking also induces a negative mass squared for the SM Higgs doublet to trigger the electroweak symmetry breaking. In this context, we investigate a possibility to solve the SM Higgs vacuum instability problem. The model includes only three free parameters (U(1)$^\\prime$ charge of the SM Higgs doublet, U(1)$^\\prime$ gauge ...

  14. Colloidal Stability & Conformational Changes in β-Lactoglobulin: Unfolding to Self-Assembly

    Directory of Open Access Journals (Sweden)

    Steven Blake

    2015-08-01

    Full Text Available A detailed understanding of the mechanism of unfolding, aggregation, and associated rheological changes is developed in this study for β-Lactoglobulin at different pH values through concomitant measurements utilizing dynamic light scattering (DLS, optical microrheology, Raman spectroscopy, and differential scanning calorimetry (DSC. The diffusion interaction parameter kD emerges as an accurate predictor of colloidal stability for this protein consistent with observed aggregation trends and rheology. Drastic aggregation and gelation were observed at pH 5.5. Under this condition, the protein’s secondary and tertiary structures changed simultaneously. At higher pH (7.0 and 8.5, oligomerizaton with no gel formation occurred. For these solutions, tertiary structure and secondary structure transitions were sequential. The low frequency Raman data, which is a good indicator of hydrogen bonding and structuring in water, has been shown to exhibit a strong correlation with the rheological evolution with temperature. This study has, for the first time, demonstrated that this low frequency Raman data, in conjunction with the DSC endotherm, can be been utilized to deconvolve protein unfolding and aggregation/gelation. These findings can have important implications for the development of protein-based biotherapeutics, where the formulation viscosity, aggregation, and stability strongly affects efficacy or in foods where protein structuring is critical for functional and sensory performance.

  15. Data of evolutionary structure change: 1EGDC-2R0MA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1EGDC-2R0MA 1EGD 2R0M C A -------LGFSFEFTEQQKEFQATARKFAREEIIPVAAE...YDKTGEYPVPLIRRAWELGLMNTHIPENCGGLGLGTFDACLISEELAYGCTGVQTAIEGNS-LGQMPIIIAGNDQQKKKYLGRMTEEPLMCAYCVTEPGAGSDVAGIKTKAEKK--GD...EYIINGQKMWITNGGKANWYFLLARSDPDPKAPANKAFTGFIVEADTPGIQIGRKEL-NMGQRCSDTRGIVFEDVKVPKENVLIGDGAGFKVAMGAFD...KERPVVAAGAVGLAQRALDEATKYALERKTFGKLLVEHQAISFMLAEMAMKVELARMSYQRAAWEVDSGRRNTYYASIAKAFAGD... 0 1EGD C

  16. Predicting free energy contributions to the conformational stability of folded proteins from the residue sequence with radial basis function networks

    Energy Technology Data Exchange (ETDEWEB)

    Casadio, R.; Fariselli, P.; Vivarelli, F. [Univ. of Bologna (Italy); Compiani, M. [Univ. of Camerino (Italy)

    1995-12-31

    Radial basis function neural networks are trained on a data base comprising 38 globular proteins of well resolved crystallographic structure and the corresponding free energy contributions to the overall protein stability (as computed partially from crystallographic analysis and partially with multiple regression from experimental thermodynamic data by Ponnuswamy and Gromiha (1994)). Starting from the residue sequence and using as input code the percentage of each residue and the total residue number of the protein, it is found with a cross-validation method that neural networks can optimally predict the free energy contributions due to hydrogen bonds, hydrophobic interactions and the unfolded state. Terms due to electrostatic and disulfide bonding free energies are poorly predicted. This is so also when other input codes, including the percentage of secondary structure type of the protein and/or residue-pair information are used. Furthermore, trained on the computed and/or experimental {Delta}G values of the data base, neural networks predict a conformational stability ranging from about 10 to 20 kcal mol{sup -1} rather independently of the residue sequence, with an average error per protein of about 9 kcal mol{sup -1}.

  17. Predicting free energy contributions to the conformational stability of folded proteins from the residue sequence with radial basis function networks.

    Science.gov (United States)

    Casadio, R; Compiani, M; Fariselli, P; Vivarelli, F

    1995-01-01

    Radial basis function neural networks are trained on a data base comprising 38 globular proteins of well resolved crystallographic structure and the corresponding free energy contributions to the overall protein stability (as computed partially from chrystallographic analysis and partially with multiple regression from experimental thermodynamic data by Ponnuswamy and Gromiha (1994)). Starting from the residue sequence and using as input code the percentage of each residue and the total residue number of the protein, it is found with a cross-validation method that neural networks can optimally predict the free energy contributions due to hydrogen bonds, hydrophobic interactions and the unfolded state. Terms due to electrostatic and disulfide bonding free energies are poorly predicted. This is so also when other input codes, including the percentage of secondary structure type of the protein and/or residue-pair information are used. Furthermore, trained on the computed and/or experimental delta G values of the data base, neural networks predict a conformational stability ranging from about 10 to 20 kcal mol-1 rather independently of the residue sequence, with an average error per protein of about 9 kcal mol-1.

  18. On the stability of D7–D7{sup ¯} probes in near-conformal backgrounds

    Energy Technology Data Exchange (ETDEWEB)

    Anguelova, Lilia, E-mail: languelova@perimeterinstitute.ca [Perimeter Institute for Theoretical Physics, Waterloo, ON N2L 2Y5 (Canada); Suranyi, Peter, E-mail: peter.suranyi@gmail.com [Dept. of Physics, University of Cincinnati, Cincinnati, OH 45221 (United States); Wijewardhana, L.C.R., E-mail: rohana.wijewardhana@gmail.com [Dept. of Physics, University of Cincinnati, Cincinnati, OH 45221 (United States)

    2014-04-15

    We investigate the perturbative stability of a nonsupersymmetric D7–D7{sup ¯} brane embedding in a particular class of type IIB backgrounds. These backgrounds are the gravitational duals of certain strongly-coupled gauge theories, that exhibit a nearly conformal regime (known as a walking regime). Previous studies in the literature have led to conflicting results as to whether the spectrum of fluctuations around the flavor D7–D7{sup ¯} embedding has a tachyonic mode or not. Here we reconsider the problem with a new analytical method and recover the previously obtained numerical results. We also point out that the earlier treatments relied on a coordinate system, in which it was not possible to take into account fluctuations of the point of confluence of the D7–D7{sup ¯} branes. Using an improved coordinate system, we confirm the presence of a normalizable tachyonic mode in this model, in agreement with the numerical calculations. Finally, we comment on the possibility of turning on worldvolume flux to stabilize the probe branes configuration.

  19. Conformation and stability properties of B17: II. Analytical investigations using differential scanning calorimetry.

    Science.gov (United States)

    Khachfe, Hassan M; Atkinson, David

    2013-04-01

    Thermal and stability properties of B17, the 17% N-terminal domain of apo B, were carried out using differential scanning calorimetry spectroscopy, where the thermal characteristics of the polypeptide were studied and analyzed. The heat capacity data of B17 showed that the protein undergoes two transitions between 50 and 90 °C, with T m's at 65.9 and 74.8 °C. While the first transition showed immediate reversibility, the second one-with the higher T m-necessitated a longer cooling (several days) period for its reversibility to be observed and both transitions could be seen in the heat capacity profile of B17. Moreover, the van't Hoff enthalpies determined via calorimetric measurements agreed with the values calculated from the CD analysis reported previously.

  20. Intramolecular CH⋯π and CH⋯O interactions in the conformational stability of benzyl methyl ether studied by matrix-isolation infrared spectroscopy and theoretical calculations

    Science.gov (United States)

    Shin-ya, Kei; Takahashi, Osamu; Katsumoto, Yukiteru; Ohno, Keiichi

    2007-02-01

    Contributions of the intramolecular CH⋯π and CH⋯O interactions to the molecular conformation of benzyl methyl ether (BME) have been investigated by matrix-isolation infrared (IR) spectroscopy combined with quantum chemical calculations. Comparative investigations have been carried out for propylbenzene. Quantum chemical calculations predict that there are two conformers for BME; for the ET conformer the methyl ether and the phenyl groups lie in the plane of the benzene ring, while for the AG conformer they are out of the plane. Comparison between the observed and calculated spectra for BME reveals that the ET and AG conformers coexist in an Ar matrix. By measuring matrix-isolation IR spectra of BME deposited at different gas temperatures, the enthalpy difference (Δ H (AG - ET)) between ET and AG conformers was determined to be -1.03 ± 0.06 kJ mol -1. The experimental and calculation results indicate that the AG conformer of BME is stabilized by the intramolecular CH⋯π and CH⋯O interactions.

  1. Boole complement elements and the direct product decomposition of R0-algebra%R0-代数的Boole可补元与直积分解

    Institute of Scientific and Technical Information of China (English)

    朱怡权

    2006-01-01

    R0-代数中引进了Boole可补元的概念,讨论了Boole可补元的一些基本性质;利用Boole可补元构造了R0-代数的一种直积分解.这些结果在一定程度上反映了R0-代数内部结构的特征,有益于从语义的角度进一步研究格值模糊逻辑系统.

  2. A study on the development of regulatory guide to stability conformation and classification criteria of low and intermediate level radioactive waste

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Geon Jae; Paek, Min Hoon; Park, Jong Gil; Han, Byeong Seop; Cheong, Jae Hak; Lee, Hae Chan; Yang, Jin Yeong; Hong, Hei Kwan; Park, Jin Baek [Korea Advanced Institute of Science and Technology, Taejon (Korea, Republic of)

    1994-01-15

    The objectives of this study are to examine basic principles and terms and to suggest and recommend definite methods and criteria necessary for the classification and stability conformation of radioactive wastes. In this study, following studies were performed : investigate the domestic regulations related with the stability conformation and classification of radioactive wastes in order to keep mutual relationship and consistency between the regulations, investigate the sources, types and characteristics of domestic radioactive wastes as a basis for this study, investigate the classification criteria and methods of others countries in a general point of view and in the view point of disposal method, select the classification criteria factors for the domestic case and general case in the both general and domestic points of view, investigate the general test items for the stability conformation of radioactive waste forms and analysis on the test items and criteria of others countries for the mined cavity disposal and shallow land disposal in the view point of disposal method, experimental leaching and immersion tests for the borate and spent resin wastes as a study on the stability conformation of waste forms, selection of acceptance criteria for the both of disposal methods in the domestic and general cases.

  3. Calcium-dependent conformational change and thermal stability of the isolated PsbO protein detected by FTIR spectroscopy.

    Science.gov (United States)

    Heredia, P; De Las Rivas, J

    2003-10-14

    The structure and function of the photosystem II PsbO extrinsic protein is under intense research, being an essential part of the biomolecular engine that carries out water oxidation and oxygen production. This paper presents a structural analysis of the isolated PsbO protein by FTIR spectroscopy, reporting detailed secondary structure quantification and changes in the secondary structure content of the protein attributed to the effect of calcium (Ca(2+)). Measurements in H(2)O and D(2)O have allowed us to see the effect of calcium on the conformation of the protein. The results indicate that (i) the protein presents a major content of beta-structure (i.e., beta-sheet, beta-strands, beta-turns) as detected by the infrared bands at 1624-1625, 1678-1679, 1688-1689 cm(-1), which account for about 38% in water and 33% in heavy water, in the presence of calcium; and (ii) the amount of this beta-structure fraction increases 7-10% in the absence of calcium, with a concomitant decrease in loops and nonordered structure. The thermal denaturation profile of the protein in the presence of calcium showed low stability with T(m) approximately 56 degrees C. This profile also shows a second phase of denaturation above 60 degrees C and the appearance of aggregation signals above 70 degrees C. Our observations indicate that calcium is able to modify the conformation of the protein at least in solution and confirm that PsbO is mainly a beta-protein where beta-sheet is the major ordered secondary structure element of the protein core.

  4. Oculocutaneous Albinism Type 1: Link between Mutations, Tyrosinase Conformational Stability, and Enzymatic Activity

    Science.gov (United States)

    Dolinska, Monika B.; Kus, Nicole; Farney, Katie; Wingfield, Paul T.; Brooks, Brian P.; Sergeev, Yuri V.

    2017-01-01

    Summary Oculocutaneous albinism Type 1 (OCA1) is an autosomal recessive disorder caused by mutations in the tyrosinase gene. Two subtypes of OCA1 have been described: severe OCA1A with complete absence of tyrosinase activity and less severe OCA1B with residual tyrosinase activity. Here, we characterize the recombinant human tyrosinase intra-melanosomal domain and mutant variants, which mimic genetic changes in both subtypes of OCA1 patients. Proteins were prepared using site-directed mutagenesis, expressed in insect larvae, purified by chromatography, and characterized by enzymatic activities- tryptophan fluorescence, and Gibbs free energy changes. The OCA1A mutants show very low protein expression, protein yield, and are enzymatically inactive. Mutants mimicking OCA1B were biochemically similar to the wild type, but exhibited lower specific activities and protein stabilities. The results are consistent with clinical data, which indicates that OCA1A mutations inactivate tyrosinase and result in severe phenotype, while OCA1B mutations partially inactive tyrosinase and results in OCA1B albinism. PMID:27775880

  5. Evaluation of the Conformational Stability of Recombinant Desulfurizing Enzymes from a Newly Isolated Rhodococcus sp.

    Science.gov (United States)

    Parravicini, Federica; Brocca, Stefania; Lotti, Marina

    2016-01-01

    Metabolic pathways of aerobic bacteria able to assimilate sulfur can provide biocatalysts for biodesulfurization of petroleum and of other sulfur-containing pollutants. Of major interest is the so-called "4S pathway," in that C-S bonds are specifically cleaved leaving the carbon skeleton of substrates intact. This pathway is carried out by four enzymes, named Dsz A, B, C, and D. In view of a possible application of recombinant Dsz enzymes in biodesulfurization treatments, we have investigated the structural features of enzymes cloned from a Rhodococcus strain isolated from polluted environmental samples and their resistance to temperature (20-95 °C) and to organic solvents (5, 10, and 20 % v/v methanol, acetonitrile, hexane, and toluene). Changes in protein structures were assessed by circular dichroism and intrinsic fluorescence spectroscopy. We found that all Dsz proteins are unfolded by temperatures in the range 45-60 °C and by all solvents tested, with the most dramatic effect being produced by toluene. These results suggest that stabilization of the biocatalysts by protein engineering will be necessary for developing biodesulfurization technologies based on Dsz enzymes.

  6. Influence of functionalized nanoparticles on conformational stability of type I collagen for possible biomedical applications.

    Science.gov (United States)

    Kandamchira, Aswathy; Selvam, Sangeetha; Marimuthu, Nidhin; Janardhanan, Sreeram Kalarical; Fathima, Nishter Nishad

    2013-12-01

    Collagen-nanoparticle interactions are vital for many biomedical applications including drug delivery and tissue engineering applications. Iron oxide nanoparticles synthesized using starch template according to our earlier reported procedures were functionalized by treating them with Gum Arabic (GA), a biocompatible polysaccharide, so as to enhance the interaction between nanoparticle surfaces and collagen. Viscosity, circular dichroism (CD) and Fourier transform infrared spectroscopy (FTIR) techniques have been used to study the collagen-nanoparticle interactions. The relative viscosity for collagen-nanoparticle conjugate was found to increase with increase in concentration of the nanoparticle within the concentration range investigated, which is due to the aggregation of protein onto the surface of nanoparticle. The CD spectra for the collagen-nanoparticle at different concentration ratios do not have much variation in the Rpn values (ratio of positive peak intensity over negative peak intensity) after functionalization with GA. The variation of molar ellipticity values for collagen-nanoparticle is due to the glycoprotein present in GA. The collagen triple helical structure is maintained after interaction with nanoparticles. The FTIR spectra of native collagen, Coll-Fs (nanoparticle without functionalization) and Coll-FsG (nanoparticle functionalized with GA) show clearly the amide I, II, III bands, with respect to collagen. The ability of polysaccharide stabilized/functionalized nanoparticles to maintain the collagen properties would help in its biomedical applications.

  7. An in silico study of the molecular basis of B-RAF activation and conformational stability

    Directory of Open Access Journals (Sweden)

    Jónsdóttir Svava

    2009-07-01

    Full Text Available Abstract Background B-RAF kinase plays an important role both in tumour induction and maintenance in several cancers and it is an attractive new drug target. However, the structural basis of the B-RAF activation is still not well understood. Results In this study we suggest a novel molecular basis of B-RAF activation based on molecular dynamics (MD simulations of B-RAFWT and the B-RAFV600E, B-RAFK601E and B-RAFD594V mutants. A strong hydrogen bond network was identified in B-RAFWT in which the interactions between Lys601 and the well known catalytic residues Lys483, Glu501 and Asp594 play an important role. It was found that several mutations, which directly or indirectly destabilized the interactions between these residues within this network, contributed to the changes in B-RAF activity. Conclusion Our results showed that the above mechanisms lead to the disruption of the electrostatic interactions between the A-loop and the αC-helix in the activating mutants, which presumably contribute to the flipping of the activation segment to an active form. Conversely, in the B-RAFD594V mutant that has impaired kinase activity, and in B-RAFWT these interactions were strong and stabilized the kinase inactive form.

  8. Vibrational spectra, NBO, HOMO-LUMO and conformational stability studies of 4-hydroxythiobenzamide.

    Science.gov (United States)

    Sambathkumar, Kuppusamy

    2015-08-05

    In this work, the experimental and theoretical study on molecular structure, vibrational spectral analysis of 4-hydroxythiobenzamide (HTB) have been reported. The solid phase FTIR (4000-400 cm(-1)) and FT-Raman spectra (3500-50 cm(-1)) were recorded. The molecular geometry, harmonic vibrational frequencies and bonding features of HTB in the ground-state have been calculated by the density functional method (B3LYP) with 6-311+G(d,p) and 6-311++G(d,p) as basis sets. Utilizing the observed FTIR and FT-Raman data, a complete vibrational assignment and analysis of the fundamental modes of the compound were carried out. Stability of the molecule arising from hyperconjugative interactions, charge delocalization has been analyzed using natural bond orbital (NBO) analysis. The results show that the value of electron density (ED) in the σ(∗) antibonding orbitals and E((2)) energies confirms the occurrence of ICT (intra-molecular charge transfer) within the molecule. The UV spectrum was measured in ethanol solution. The energy and oscillator strength calculated by time-dependent density functional theory (TD-DFT) correlates with the experimental findings. The calculated molecular electrostatic potential (MESP), HOMO and LUMO energies show that charge transfer occurs within the molecule. Besides, the simulated infrared and Raman spectra of the title compound which show good agreement with observed spectra. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Concurrent Increases and Decreases in Local Stability and Conformational Heterogeneity in Cu, Zn Superoxide Dismutase Variants Revealed by Temperature-Dependence of Amide Chemical Shifts.

    Science.gov (United States)

    Doyle, Colleen M; Rumfeldt, Jessica A; Broom, Helen R; Sekhar, Ashok; Kay, Lewis E; Meiering, Elizabeth M

    2016-03-08

    The chemical shifts of backbone amide protons in proteins are sensitive reporters of local structural stability and conformational heterogeneity, which can be determined from their readily measured linear and nonlinear temperature-dependences, respectively. Here we report analyses of amide proton temperature-dependences for native dimeric Cu, Zn superoxide dismutase (holo pWT SOD1) and structurally diverse mutant SOD1s associated with amyotrophic lateral sclerosis (ALS). Holo pWT SOD1 loses structure with temperature first at its periphery and, while having extremely high global stability, nevertheless exhibits extensive conformational heterogeneity, with ∼1 in 5 residues showing evidence for population of low energy alternative states. The holo G93A and E100G ALS mutants have moderately decreased global stability, whereas V148I is slightly stabilized. Comparison of the holo mutants as well as the marginally stable immature monomeric unmetalated and disulfide-reduced (apo(2SH)) pWT with holo pWT shows that changes in the local structural stability of individual amides vary greatly, with average changes corresponding to differences in global protein stability measured by differential scanning calorimetry. Mutants also exhibit altered conformational heterogeneity compared to pWT. Strikingly, substantial increases as well as decreases in local stability and conformational heterogeneity occur, in particular upon maturation and for G93A. Thus, the temperature-dependence of amide shifts for SOD1 variants is a rich source of information on the location and extent of perturbation of structure upon covalent changes and ligand binding. The implications for potential mechanisms of toxic misfolding of SOD1 in disease and for general aspects of protein energetics, including entropy-enthalpy compensation, are discussed.

  10. Temperature and Stretching Effects on Complementarity Determining Regions (CDRs Conformation and Stability of Nimotuzumab F(ab-Fragment

    Directory of Open Access Journals (Sweden)

    T.S. Humani

    2015-04-01

    Full Text Available Nimotuzumab is a humanized monoclonal antibody (mAb, a potential anticancer against epidermal growth factor receptor (EGFRoverexpressed by glioma, head and neck, lung, ovarium, and colon cancers. The combination of its use with both external and internal beam radiotherapies showed improvement of the therapeutic effect. However, the high molecular weight slows its uptake on tumor cells. In a recent development, nimotuzumab has been fragmented and then labeled using diagnostic and therapeutic radionuclides, such as gallium-68, yttrium-90, lutetium-177, and holmium-166. In that preparation, nimotuzumab is often conditioned in various environments with variations of pH, temperature and the presence of other compounds. In this research, molecular dynamics (MD simulation have been carried out to study the CDRs conformational change of nimotuzumab due to the effect of temperature, and also steered molecular dynamics (SMD simulation to study the stability of nimotuzumab domain as a result of external forces. The simulations were performed using the Not Just Another Molecular Dynamics (NAMD program package and the analysis was performed with the Visual Molecular Dynamics (VMD program package. Based on the stability analysis of each residue on the heavy chain, the active site (CDR3 region that is at residues numbered 98 (Tryptophan and 99 (Phenylalanine has the highest conformational changes. On the light chain, the change occurs at residues numbered 1 (Aspartat, 127 (Serin, and 186 (Tyrosine; and that none of that residues is part of active site or CDRs region of the light chain. The SMD simulation was carried out by fixing the N-terminal end of the heavy chain and applying external forces to the C-terminal end. The pulling was set at a constant velocity of 0.5 Å/ps. The force peak arising at the beginning of the unfolding process is 1226 pN. This force was allegedly caused by the rupture of hydrogen bonds between the heavy chain residue VAL211 (Valine

  11. 模糊集间的R0-相似关系及其性质%R0 -similarity relation between fuzzy sets and its properties

    Institute of Scientific and Technical Information of China (English)

    刘杰; 吴洪博

    2011-01-01

    将王国俊教授在R0-型逻辑系统中建立的R0-蕴涵算子应用于模糊数学理论之中,在非空集合X为论域的模糊集族F(X)上定义了一种新型运算- R0蕴含运算,并讨论了F(X)上R0-蕴含运算的一些基本性质.通过R0-蕴含运算在F(X)上定义了一个二元模糊相似关系- R0-相似关系,并对其性质进行了较为详细的讨论.在有限论域X确定的模糊集族F(X)上给出了几个R0-相似关系的具体实例.%Ro -implication operator proposed by Professor Wang Guojun in the Ro -type logic system has been applied to the fuzzy mathematical theory,and a new kind of computation- Ro -implication operation, is defined on the family F(X) of fuzzy sets, and its basic properties have been discussed.Then, a binary fuzzy similarity relation- Ro -similarity relation on F(X) is defined through the Ro implication,and its properties are discussed in detail.Finally,several examples of Ro -similarity relation are provided by the Ro implication operator on F(X) with the finite domain Xnot only the results of this paper make an application of the R0-type logic system,but also enrich the methods of studying fuzzy mathematics.

  12. Correlating excipient effects on conformational and storage stability of an IgG1 monoclonal antibody with local dynamics as measured by hydrogen/deuterium-exchange mass spectrometry.

    Science.gov (United States)

    Manikwar, Prakash; Majumdar, Ranajoy; Hickey, John M; Thakkar, Santosh V; Samra, Hardeep S; Sathish, Hasige A; Bishop, Steven M; Middaugh, C Russell; Weis, David D; Volkin, David B

    2013-07-01

    The effects of sucrose and arginine on the conformational and storage stability of an IgG1 monoclonal antibody (mAb) were monitored by differential scanning calorimetry (DSC) and size-exclusion chromatography (SEC), respectively. Excipient effects on protein physical stability were then compared with their effects on the local flexibility of the mAb in solution at pH 6, 25°C using hydrogen/deuterium-exchange mass spectrometry (H/D-MS). Compared with a 0.1 M NaCl control, sucrose (0.5 M) increased conformational stability (T(m) values), slowed the rate of monomer loss, reduced the formation of insoluble aggregates, and resulted in a global trend of small decreases in local flexibility across most regions of the mAb. In contrast, the addition of arginine (0.5 M) decreased the mAb's conformational stability, increased the rate of loss of monomer with elevated levels of soluble and insoluble aggregates, and led to significant increases in the local flexibility in specific regions of the mAb, most notably within the constant domain 2 of the heavy chain (C(H)2). These results provide new insights into the effect of sucrose and arginine on the local dynamics of IgG1 domains as well as preliminary correlations between local flexibility within specific segments of the C(H)2 domain (notably heavy chain 241-251) and the mAb's overall physical stability.

  13. Control of the PEO chain conformation on nanoparticles by adsorption of PEO-block-poly(L-lysine) copolymers and its significance on colloidal stability and protein repellency.

    Science.gov (United States)

    Louguet, Stéphanie; Kumar, Anitha C; Guidolin, Nicolas; Sigaud, Gilles; Duguet, Etienne; Lecommandoux, Sébastien; Schatz, Christophe

    2011-11-01

    The physical adsorption of PEO(n)-b-PLL(m) copolymers onto silica nanoparticles and the related properties of poly(ethylene oxide) (PEO)-coated particles were studied as a function of the block copolymer composition. Copolymers adopt an anchor-buoy conformation at the particle surface owing to a preferential affinity of poly(L-lysine) (PLL) blocks with the silica surface over PEO blocks when a large excess of copolymer is used. The interdistance between PEO chains at particle surface is highly dependent on the size of PLL segments; a dense brush of PEO is obtained for short PLL blocks (DP = 10), whereas PEO chains adopt a so-called interacting "mushroom" conformation for large PLL blocks (DP = 270). The size of the PEO blocks does not really influence the copolymer surface density, but it has a strong effect on the PEO layer thickness as expected. Salt and protein stability studies led to similar conclusions about the effectiveness of a PEO layer with a dense brush conformation to prevent colloidal aggregation and protein adsorption. Besides, a minimal PEO length is required to get full stabilization properties; as a matter of fact, both PEO(45)-b-PLL(10) and PEO(113)-b-PLL(10) give rise to a PEO brush conformation but only the latter copolymer efficiently stabilizes the particles in the presence of salt or proteins.

  14. Conformational and thermal stability improvements for the large-scale production of yeast-derived rabbit hemorrhagic disease virus-like particles as multipurpose vaccine.

    Directory of Open Access Journals (Sweden)

    Erlinda Fernández

    Full Text Available Recombinant virus-like particles (VLP antigenically similar to rabbit hemorrhagic disease virus (RHDV were recently expressed at high levels inside Pichia pastoris cells. Based on the potential of RHDV VLP as platform for diverse vaccination purposes we undertook the design, development and scale-up of a production process. Conformational and stability issues were addressed to improve process control and optimization. Analyses on the structure, morphology and antigenicity of these multimers were carried out at different pH values during cell disruption and purification by size-exclusion chromatography. Process steps and environmental stresses in which aggregation or conformational instability can be detected were included. These analyses revealed higher stability and recoveries of properly assembled high-purity capsids at acidic and neutral pH in phosphate buffer. The use of stabilizers during long-term storage in solution showed that sucrose, sorbitol, trehalose and glycerol acted as useful aggregation-reducing agents. The VLP emulsified in an oil-based adjuvant were subjected to accelerated thermal stress treatments. None to slight variations were detected in the stability of formulations and in the structure of recovered capsids. A comprehensive analysis on scale-up strategies was accomplished and a nine steps large-scale production process was established. VLP produced after chromatographic separation protected rabbits against a lethal challenge. The minimum protective dose was identified. Stabilized particles were ultimately assayed as carriers of a foreign viral epitope from another pathogen affecting a larger animal species. For that purpose, a linear protective B-cell epitope from Classical Swine Fever Virus (CSFV E2 envelope protein was chemically coupled to RHDV VLP. Conjugates were able to present the E2 peptide fragment for immune recognition and significantly enhanced the peptide-specific antibody response in vaccinated pigs

  15. Conformational and Thermal Stability Improvements for the Large-Scale Production of Yeast-Derived Rabbit Hemorrhagic Disease Virus-Like Particles as Multipurpose Vaccine

    Science.gov (United States)

    Méndez, Lídice; González, Nemecio; Parra, Francisco; Martín-Alonso, José M.; Limonta, Miladys; Sánchez, Kosara; Cabrales, Ania; Estrada, Mario P.; Rodríguez-Mallón, Alina; Farnós, Omar

    2013-01-01

    Recombinant virus-like particles (VLP) antigenically similar to rabbit hemorrhagic disease virus (RHDV) were recently expressed at high levels inside Pichia pastoris cells. Based on the potential of RHDV VLP as platform for diverse vaccination purposes we undertook the design, development and scale-up of a production process. Conformational and stability issues were addressed to improve process control and optimization. Analyses on the structure, morphology and antigenicity of these multimers were carried out at different pH values during cell disruption and purification by size-exclusion chromatography. Process steps and environmental stresses in which aggregation or conformational instability can be detected were included. These analyses revealed higher stability and recoveries of properly assembled high-purity capsids at acidic and neutral pH in phosphate buffer. The use of stabilizers during long-term storage in solution showed that sucrose, sorbitol, trehalose and glycerol acted as useful aggregation-reducing agents. The VLP emulsified in an oil-based adjuvant were subjected to accelerated thermal stress treatments. None to slight variations were detected in the stability of formulations and in the structure of recovered capsids. A comprehensive analysis on scale-up strategies was accomplished and a nine steps large-scale production process was established. VLP produced after chromatographic separation protected rabbits against a lethal challenge. The minimum protective dose was identified. Stabilized particles were ultimately assayed as carriers of a foreign viral epitope from another pathogen affecting a larger animal species. For that purpose, a linear protective B-cell epitope from Classical Swine Fever Virus (CSFV) E2 envelope protein was chemically coupled to RHDV VLP. Conjugates were able to present the E2 peptide fragment for immune recognition and significantly enhanced the peptide-specific antibody response in vaccinated pigs. Overall these results

  16. Data of evolutionary structure change: 1ELCA-2R0LA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1ELCA-2R0LA 1ELC 2R0L A A VVGGTEAQRNSWPSQISLQYRSGSSWAHTCGGTLIRQNW...TFGIEKYIPYTLYSVFNPS-DHDLVLIRLKKKGDRCATRSQFVQPICLPEPGSTFPAGHKCQIAGWGHLDENVSGYSSSLREALVPLVADHKCSSPEVYGADISPNMLCA...>A 1ELCA LLRLA----QSVTL EE...entryChain> 1ELC A 1ELCA 2 1ELC A 1ELCA

  17. Silicon/Organic Hybrid Solar Cells with 16.2% Efficiency and Improved Stability by Formation of Conformal Heterojunction Coating and Moisture-Resistant Capping Layer.

    Science.gov (United States)

    He, Jian; Gao, Pingqi; Yang, Zhenhai; Yu, Jing; Yu, Wei; Zhang, Yu; Sheng, Jiang; Ye, Jichun; Amine, Joseph Chen; Cui, Yi

    2017-02-02

    Silicon/poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) heterojunction solar cells with 16.2% efficiency and excellent stability are fabricated on pyramid-textured silicon substrates by applying a water-insoluble ester as capping layer. It shows that conformal coating of PEDOT:PSS on textured silicon can greatly improve the junction quality with the main stability failure routes related to the moisture-induced poly(3,4-ethylenedioxythiophene) aggregations and the tunneling silicon oxide autothickening.

  18. R0-modeling as a tool for early warning and surveillance of exotic vector borne diseases in Denmark

    DEFF Research Database (Denmark)

    Bødker, Rene

    2011-01-01

    the surveillance on periods and areas with high R0 estimates even if the actual value of these estimates are difficult to interpret. Furthermore running R0 models on historic outbreaks in Europe may be used to fit estimates for R0 for these data. When comparing the model R0 to the observed value of R0 a correction...

  19. R0-modeling as a tool for early warning and surveillance of exotic vector borne diseases in Denmark

    DEFF Research Database (Denmark)

    Bødker, Rene; Kristensen, Birgit; Græsbøll, Kaare;

    with high R0 estimates even if the actual value of these estimates are difficult to interpret. Furthermore running R0 models on historic outbreaks in Europe may be used to fit estimates for R0 for these data. When comparing the model R0 to the observed value of R0 a correction factor is obtained that may...

  20. Local conformational stability of HIV-1 gp120 in unliganded and CD4-bound states as defined by amide hydrogen/deuterium exchange.

    Science.gov (United States)

    Kong, Leopold; Huang, Chih-Chin; Coales, Stephen J; Molnar, Kathleen S; Skinner, Jeff; Hamuro, Yoshitomo; Kwong, Peter D

    2010-10-01

    The binding reaction of the HIV-1 gp120 envelope glycoprotein to the CD4 receptor involves exceptional changes in enthalpy and entropy. Crystal structures of gp120 in unliganded and various ligand-bound states, meanwhile, reveal an inner domain able to fold into diverse conformations, a structurally invariant outer domain, and, in the CD4-bound state, a bridging sheet minidomain. These studies, however, provide only hints as to the flexibility of each state. Here we use amide hydrogen/deuterium exchange coupled to mass spectrometry to provide quantifications of local conformational stability for HIV-1 gp120 in unliganded and CD4-bound states. On average, unliganded core gp120 displayed >10,000-fold slower exchange of backbone-amide hydrogens than a theoretically unstructured protein of the same composition, with binding by CD4 reducing the rate of gp120 amide exchange a further 10-fold. For the structurally constant CD4, alterations in exchange correlated well with alterations in binding surface (P value = 0.0004). For the structurally variable gp120, however, reductions in flexibility extended outside the binding surface, and regions of expected high structural diversity (inner domain/bridging sheet) displayed roughly 20-fold more rapid exchange in the unliganded state than regions of low diversity (outer domain). Thus, despite an extraordinary reduction in entropy, neither unliganded gp120 nor free CD4 was substantially unstructured, suggesting that most of the diverse conformations that make up the gp120 unliganded state are reasonably ordered. The results provide a framework for understanding how local conformational stability influences entropic change, conformational diversity, and structural rearrangements in the gp120-CD4 binding reaction.

  1. Investigating the in Vitro Thermal Stability and Conformational Flexibility of Estrogen Receptors as Potential Key Factors of Their in Vivo Activity.

    Science.gov (United States)

    Le Grand, Adélaïde; André-Leroux, Gwenaëlle; Marteil, Gaëlle; Duval, Hélène; Sire, Olivier; Le Tilly, Véronique

    2015-06-30

    Among hormone-inducible transcription factors, estrogen receptors (ERs) play important roles in tissue growth and differentiation, via either direct or indirect binding, in the nucleus, to specific DNA targets called estrogen responsive elements (EREs), or through nongenomic pathways. In humans, two estrogen receptor isoforms (hERs), designated hERα and hERβ, have been identified. These two hERs, encoded by genes located on distinct chromosomes, exhibit divergent tissue-specific functions and different subcellular distributions depending on their binding status, free or complexed to their cognate ligands. Because it is hypothesized that such distinct behaviors may arise from various conformational stabilities and flexibilities, the effect of salt concentration and temperature was studied on the free and estrogen-activated hERα and hERβ. Our results show that the conformational stability of hERβ is weakly modulated by salt concentration as opposed to hERα. In addition, we show that the estrogen-bound hERs exhibit a more constrained structure than the unliganded ones and that their conformational flexibility is more affected by diethylstilbestrol binding than that of estradiol, 4-hydroxytamoxifen, or raloxifen. In line with these results, conformational analysis and computational docking were performed on hERα and hERβ, which confer molecular support of a diethylstilbestrol-induced restrained flexibility as compared to other ligands. We found that Trp383 in hERα and Trp335 in hERβ can closely interact with the NR-box motif of the H12 helix and act as a gatekeeper of the agonist-bound versus antagonist-bound conformations. Altogether, our study contributes to an improved knowledge of the diverse physicochemical properties of full-length hERs, which will help in our understanding of their distinct cellular roles in various cellular contexts.

  2. A study of the conformation and stability of nitroxide free radicals; Etude de la conformation et de la stabilite de radicaux libres nitroxydes

    Energy Technology Data Exchange (ETDEWEB)

    Briere, R. [Commissariat a l' Energie Atomique, Grenoble (France). Centre d' Etudes Nucleaires

    1969-03-01

    The first part of this study is an application of nuclear magnetic resonance to the determination of the sign and magnitude of the long range nuclear-electron spin-spin couplings in the free radical nitroxide derived from piperidine. It has been shown that the coupling constants of the protons {gamma} to the nitrogen atom have a pronounced spatial dependence as do the protons in the {beta} position, a point which has not been brought out by previous investigations. Conformational analysis of these compounds has been carried out by measurement of the effect of temperature on the NMR spectra at 310 MHz. The synthesis of di-t-Bu nitroxide labelled with C{sup 13} in the {alpha}-position made possible the unambiguous determination of the corresponding {sup 13}C nuclear-electron spin-spin coupling constant, a parameter which had not previously been measured. The coupling constants measured in the 2,2,6,6-tetramethyl piperidine series could then be attributed to the {sup 13}C atoms in the {beta}-position and their variation related to the conformations of the heterocycles. This constitutes the second part of the work reported here. The final section is devoted to a study of the decomposition of an unstable nitroxide having a hydrogen atom in the p-position. This decomposition is bimolecular and the primary isotope effect shows that the rupture. of the C-H bond is involved. From this one can conclude that a nitroxide is stable when the different groups attached to the nitrogen atom cannot give rise to a decomposition either intra molecularly, if the molecular geometry is suitable, or inter molecularly by dimerisation through attack on a different center of a neighbouring molecule thus leading to a fragmentation or a disproportionation. (author) [French] La premiere partie est une application de la resonance magnetique nucleaire a la determination du signe et de la grandeur des couplages a longue distance dans des radicaux libres nitroxydes piperidiniques. Il est montre que

  3. Properties of an Inward-Facing State of LeuT: Conformational Stability and Substrate Release

    OpenAIRE

    Grouleff, Julie; Søndergaard, Siri; Koldsø, Heidi; Schiøtt, Birgit

    2015-01-01

    The leucine transporter (LeuT) is a bacterial homolog of the human monoamine transporters, which are important pharmaceutical targets. There are no high-resolution structures of the human transporters available; however, LeuT has been crystallized in several different conformational states. Recently, an inward-facing conformation of LeuT was solved revealing an unexpectedly large movement of transmembrane helix 1a (TM1a). We have performed molecular dynamics simulations of the mutated and wil...

  4. Characterization of Pre-F-GCN4t, a Modified Human Respiratory Syncytial Virus Fusion Protein Stabilized in a Noncleaved Prefusion Conformation.

    Science.gov (United States)

    Blais, Normand; Gagné, Martin; Hamuro, Yoshitomo; Rheault, Patrick; Boyer, Martine; Steff, Ann-Muriel; Baudoux, Guy; Dewar, Vincent; Demers, Josée; Ruelle, Jean-Louis; Martin, Denis

    2017-07-01

    The human respiratory syncytial virus (hRSV) fusion (F) protein is considered a major target of the neutralizing antibody response to hRSV. This glycoprotein undergoes a major structural shift from the prefusion (pre-F) to the postfusion (post-F) state at the time of virus-host cell membrane fusion. Recent evidences suggest that the pre-F state is a superior target for neutralizing antibodies compared to the post-F state. Therefore, for vaccine purposes, we have designed and characterized a recombinant hRSV F protein, called Pre-F-GCN4t, stabilized in a pre-F conformation. To show that Pre-F-GCN4t does not switch to a post-F conformation, it was compared with a recombinant post-F molecule, called Post-F-XC. Pre-F-GCN4t was glycosylated and trimeric and displayed a conformational stability different from that of Post-F-XC, as shown by chemical denaturation. Electron microscopy analysis suggested that Pre-F-GCN4t adopts a lollipop-like structure. In contrast, Post-F-XC had a typical elongated conical shape. Hydrogen/deuterium exchange mass spectrometry demonstrated that the two molecules had common rigid folding core and dynamic regions and provided structural insight for their biophysical and biochemical properties and reactivity. Pre-F-GCN4t was shown to deplete hRSV-neutralizing antibodies from human serum more efficiently than Post-F-XC. Importantly, Pre-F-GCN4t was also shown to bind D25, a highly potent monoclonal antibody specific for the pre-F conformation. In conclusion, this construct presents several pre-F characteristics, does not switch to the post-F conformation, and presents antigenic features required for a protective neutralizing antibody response. Therefore, Pre-F-GCN4t can be considered a promising candidate vaccine antigen.IMPORTANCE Human respiratory syncytial virus (RSV) is a global leading cause of infant mortality and adult morbidity. The development of a safe and efficacious RSV vaccine remains an important goal. The RSV class I fusion (F

  5. A new method for the characterization of strain-specific conformational stability of protease-sensitive and protease-resistant PrPSc.

    Directory of Open Access Journals (Sweden)

    Laura Pirisinu

    Full Text Available Although proteinacious in nature, prions exist as strains with specific self-perpetuating biological properties. Prion strains are thought to be associated with different conformers of PrP(Sc, a disease-associated isoform of the host-encoded cellular protein (PrP(C. Molecular strain typing approaches have been developed which rely on the characterization of protease-resistant PrP(Sc. However, PrP(Sc is composed not only of protease-resistant but also of protease-sensitive isoforms. The aim of this work was to develop a protocol for the molecular characterization of both, protease-resistant and protease-sensitive PrP(Sc aggregates. We first set up experimental conditions which allowed the most advantageous separation of PrP(C and PrP(Sc by means of differential centrifugation. The conformational solubility and stability assay (CSSA was then developed by measuring PrP(Sc solubility as a function of increased exposure to GdnHCl. Brain homogenates from voles infected with human and sheep prion isolates were analysed by CSSA and showed strain-specific conformational stabilities, with mean [GdnHCl](1/2 values ranging from 1.6 M for MM2 sCJD to 2.1 for scrapie and to 2.8 M for MM1/MV1 sCJD and E200K gCJD. Interestingly, the rank order of [GdnHCl](1/2 values observed in the human and sheep isolates used as inocula closely matched those found following transmission in voles, being MM1 sCJD the most resistant (3.3 M, followed by sheep scrapie (2.2 M and by MM2 sCJD (1.6 M. In order to test the ability of CSSA to characterise protease-sensitive PrP(Sc, we analysed sheep isolates of Nor98 and compared them to classical scrapie isolates. In Nor98, insoluble PrP(Sc aggregates were mainly protease-sensitive and showed a conformational stability much lower than in classical scrapie. Our results show that CSSA is able to reveal strain-specified PrP(Sc conformational stabilities of protease-resistant and protease-sensitive PrP(Sc and that it is a valuable tool

  6. Insulin degrading enzyme induces a conformational change in varicella-zoster virus gE, and enhances virus infectivity and stability.

    Directory of Open Access Journals (Sweden)

    Qingxue Li

    Full Text Available Varicella-zoster virus (VZV glycoprotein E (gE is essential for virus infectivity and binds to a cellular receptor, insulin-degrading enzyme (IDE, through its unique amino terminal extracellular domain. Previous work has shown IDE plays an important role in VZV infection and virus cell-to-cell spread, which is the sole route for VZV spread in vitro. Here we report that a recombinant soluble IDE (rIDE enhances VZV infectivity at an early step of infection associated with an increase in virus internalization, and increases cell-to-cell spread. VZV mutants lacking the IDE binding domain of gE were impaired for syncytia formation and membrane fusion. Pre-treatment of cell-free VZV with rIDE markedly enhanced the stability of the virus over a range of conditions. rIDE interacted with gE to elicit a conformational change in gE and rendered it more susceptible to proteolysis. Co-incubation of rIDE with gE modified the size of gE. We propose that the conformational change in gE elicited by IDE enhances infectivity and stability of the virus and leads to increased fusogenicity during VZV infection. The ability of rIDE to enhance infectivity of cell-free VZV over a wide range of incubation times and temperatures suggests that rIDE may be useful for increasing the stability of varicella or zoster vaccines.

  7. Analysis of the conformation and thermal stability of the high-affinity IgE Fc receptor β chain polymorphic proteins.

    Science.gov (United States)

    Terada, Tomoyoshi; Takahashi, Teppei; Arikawa, Hajime; Era, Seiichi

    2016-07-01

    The high-affinity IgE Fc receptor (FcεRI) β chain acts as a signal amplifier through the immunoreceptor tyrosine-based activation motif in its C-terminal intracellular region. Polymorphisms in FcεRI β have been linked to atopy, asthma, and allergies. We investigated the secondary structure, conformation, and thermal stability of FcεRI β polymorphic (β-L172I, β-L174V, and β-E228G) proteins. Polymorphisms did not affect the secondary structure and conformation of FcεRI β. However, we calculated Gibbs free energy of unfolding (ΔGunf) and significant differences were observed in ΔGunf values between the wild-type FcεRI β (β-WT) and β-E228G. These results suggested that β-E228G affected the thermal stability of FcεRI β. The role of β-E228G in biological functions and its involvement in allergic reactions have not yet been elucidated in detail; therefore, differences in the thermal stability of β-E228G may affect the function of FcεRI β.

  8. Magnetostructural coupling, magnetic ordering, and cobalt spin reorientation in metallic P r0.5S r0.5Co O3 cobaltite

    Science.gov (United States)

    García-Muñoz, José Luis; Padilla-Pantoja, Jessica; Torrelles, Xavier; Blasco, Javier; Herrero-Martín, Javier; Bozzo, Bernat; Rodríguez-Velamazán, José A.

    2016-07-01

    In half-doped P r0.50A0.50Co O3 metallic perovskites, the spin-lattice coupling brings about distinct magnetostructural transitions for A =Ca and A =Sr at temperatures close to ˜100 K. However, the ground magnetic properties of P r0.50S r0.50Co O3 (PSCO) strongly differ from P r0.50C a0.50Co O3 ones, where a partial P r3 + to P r4 + valence shift and Co spin transition makes the system insulating below the transition. This paper investigates and describes the relationship between the I m m a →I 4 /m c m symmetry change [Padilla-Pantoja, García-Muñoz, Bozzo, Jirák, and Herrero-Martín, Inorg. Chem. 53, 12297 (2014)] and the original magnetic behavior of PSCO versus temperature and external magnetic fields. The FM1 and FM2 ferromagnetic phases, above and below the magnetostructural transition (TS 1˜120 K ) have been investigated. The FM2 phase of PSCO is composed of [100] FM domains, with magnetic symmetry I m'm'a (mx≠0 , mz=0 ). The magnetic space group of the FM1 phase is F m'm'm (with mx=my ). Neutron data analyses in combination with magnetometry and earlier reports results agrees with a reorientation of the magnetization axis by 45∘ within the a b plane across the transition, in which the system retains its metallic character. The presence below TS 1 of conjugated magnetic domains, both of F m'm'm symmetry but having perpendicular spin orientations along the diagonals in the x y plane of the tetragonal unit cell, is at the origin of the anomalies observed in the macroscopic magnetization. A relatively small field μ0H [⊥ z ] ≳30 mT is able to reorient the magnetization within the a b plane, whereas a higher field (μ0H [∥z ] ≳1.2 T at 2 K) is necessary to align the Co moments perpendicular to the a b plane. Such a spin reorientation, in which the orbital and spin components of the Co moment rotate joined by 45∘, was not observed previously in analogous cobaltites without praseodymium.

  9. Switchable proline derivatives: tuning the conformational stability of the collagen triple helix by pH changes.

    Science.gov (United States)

    Siebler, Christiane; Erdmann, Roman S; Wennemers, Helma

    2014-09-22

    (4S)-Aminoproline is introduced as a pH-sensitive probe for tuning the conformational properties of peptides and proteins. The pH-triggered flip of the ring puckering and the formation/release of a transannular H bond were used to switch the formation of collagen triple helices on and off reversibly.

  10. Effects of salts from the Hofmeister series on the conformational stability, aggregation propensity, and local flexibility of an IgG1 monoclonal antibody.

    Science.gov (United States)

    Majumdar, Ranajoy; Manikwar, Prakash; Hickey, John M; Samra, Hardeep S; Sathish, Hasige A; Bishop, Steven M; Middaugh, C Russell; Volkin, David B; Weis, David D

    2013-05-14

    This work examines the effect of three anions from the Hofmeister series (sulfate, chloride, and thiocyanate) on the conformational stability and aggregation rate of an IgG1 monoclonal antibody (mAb) and corresponding changes in the mAb's backbone flexibility (at pH 6 and 25 °C). Compared to a 0.1 M NaCl control, thiocyanate (0.5 M) decreased the melting temperatures (Tm) for three observed conformational transitions within the mAb by 6-9 °C, as measured by differential scanning calorimetry. Thiocyanate also accelerated the rate of monomer loss at 40 °C over 12 months, as monitored by size exclusion chromatography. Backbone flexibility, as measured via H/D exchange mass spectrometry, increased in two segments in the CH2 domain with more subtle changes across several additional regions. Chloride (0.5 M) caused slight increases in the Tm values, small changes in aggregation rate, and minimal yet consistent decreases in flexibility across various domains with larger effects noted within the VL, CH1, and CH3 domains. In contrast, 0.5 M sulfate increased Tm values, had small stabilizing influences on aggregate formation over time, yet substantially increased the flexibility of two specific regions in the CH1 and VL domains. While thiocyanate-induced conformational destabilization of the mAb correlated with increased local flexibility of specific regions in the CH2 domain (especially residues 241-251 in the heavy chain), the stabilizing anion sulfate did not affect these CH2 regions.

  11. R0-代数的(λ,μ)-fuzzy滤子理论%The Theory of (λ,μ)-fuzzy Filters in R0-algebras

    Institute of Scientific and Technical Information of China (English)

    秦学成; 刘春辉

    2012-01-01

    In this paper, the concepts of (λ,μ)-fuzzy filters are introduced in R0-algebras, where λ,μ are any two elements of {∈,q,∈∧q,∈∧q} with λ≠ ∈∧q,by using the belongs to relation ( ∈) and quasi-coincidence with relation (q) between fuzzy points and fuzzy sets. The relations among them are discussed; Someequivalent conditions of (∈,∈∧q)-fuzzy filters are obtained. The conditions of (∈ ,∈: Vq-fuzzy filters to be (∈,∈ )-fuzzy filters and a fuzzy set to be a (q, ∈∧ q)-fuzzy filters are given.%利用模糊点与模糊集之间的属于关系(∈)和拟重合关系(q)在R0-代数中引入了(λ,μ)-fuzzy滤子的概念,其中λ和μ是集合{∈,q,∈∨q,∈∧q}中的任意元素且λ≠∈∧q,并讨论它们的性质和相互关系;获得(∈,∈∨ q)-fuzzy滤子的若干等价刻画;给出(∈,∈∨q)-fuzzy滤子成为(∈,∈)-fuzzy滤子以及一个模糊集成为(q,∈∨ q)-fuzzy滤子的条件.

  12. R0 y algunas generalizaciones en autómatas celulares

    OpenAIRE

    Hernández Gómez, Juan Carlos

    2008-01-01

    Cuando se hace la modelación de procesos epidemiológicos mediante ecuaciones diferenciales gran importancia tiene el análisis del llamado número reproductivo básico (R0) sin embargo, cuando se modela mediante autómatas celulares no se tiene una cantidad similar. En este trabajo proponemos la definición de R0 en autómatas celulares, damos dicha definición y se generaliza la definición para sistemas más complejos, con heterogeneidades temporales y geográficas.

  13. Effects of hesperidin, a flavanone glycoside interaction on the conformation, stability, and aggregation of lysozyme: multispectroscopic and molecular dynamic simulation studies?

    Science.gov (United States)

    Ratnaparkhi, Aditi; Muthu, Shivani A; Shiriskar, Sonali M; Pissurlenkar, Raghuvir R S; Choudhary, Sinjan; Ahmad, Basir

    2015-09-01

    Hesperidin (HESP), a flavanone glycoside, shows high antioxidant properties and possess ability to go through the blood-brain barrier. Therefore, it could be a potential drug molecule against aggregation based diseases such as Alzheimer's, Parkinson's, and systemic amyloidoses. In this work, we investigated the potential of HESP to interact with hen egg-white lysozyme (HEWL) monomer and prevent its aggregation. The HESP-HEWL binding studies were performed using a fluorescence quenching technique, molecular docking and molecular dynamics simulations. We found a strong interaction of HESP with the lysozyme monomer (Ka, ~ 5 × 10(4) M(-1)) mainly through hydrogen bonding, water bridges, and hydrophobic interactions. We showed that HESP molecule spanned the highly aggregation prone region (amino acid residues 48-101) of HEWL and prevented its fibrillar aggregation. Further, we found that HESP binding completely inhibited amorphous aggregation of the protein induced by disulfide-reducing agent tries-(2-carboxyethyl) phosphine. Conformational and stability studies as followed by various tertiary and secondary structure probes revealed that HESP binding only marginally affected the lysozyme monomer conformation and increased both stability and reversibility of the protein against thermal denaturation. Future studies should investigate detail effects of HESP on solvent dynamics, structure, and toxicity of various aggregates. The answers to these questions will not only target the basic sciences, but also have application in biomedical and biotechnological sciences.

  14. Fundamental insights into conformational stability and orbital interactions of antioxidant (+)-catechin species and complexation of (+)-catechin with zinc(II) and oxovanadium(IV)

    Science.gov (United States)

    Yasarawan, Nuttawisit; Thipyapong, Khajadpai; Sirichai, Somsak; Ruangpornvisuti, Vithaya

    2013-09-01

    Conformational stability of (+)-catechin species in water has been examined with density functional theory, associated with the polarizable continuum model (PCM) of solvation. Factors such as electron delocalization, lone-pair electron donation and intramolecular hydrogen bonding substantially contribute to the conformational stabilization. Upon deprotonation, the HOMO and LUMO energies for (+)-catechin are both elevated; the energy gaps for the deprotonated species are narrower than the energy gap for the neutral species. The preferential deprotonation occurs at the C3'-, C5-, C7- and C4'-OH groups successively. The pKa value at 9.3 predicted for the most acidic OH group agrees well with previous experimental data; however the values are overestimated for the less acidic OH groups due to limitations of the PCM for charged solutes and/or complex nature of true deprotonation pathways. Formation of hydrogen radicals should be promoted at high pH values following the bond dissociation enthalpies. Complexation of (+)-catechin with either zinc(II) or oxovanadium(IV) is favored at the 1:1 metal-to-ligand (M:L) mole ratio, with the oxovanadium(IV) complex showing higher reaction preference. At M:L = 1:2, formation of two isomeric complexes are plausible for each type of metal ion. Effects of stoichiometry and isomerism on the computational spectral features of the possibly formed metal complexes have been described.

  15. Recombinant expression and purification of T4 phage Hoc, Soc, gp23, gp24 proteins in native conformations with stability studies.

    Directory of Open Access Journals (Sweden)

    Paulina Miernikiewicz

    Full Text Available Understanding the biological activity of bacteriophage particles is essential for rational design of bacteriophages with defined pharmacokinetic parameters and to identify the mechanisms of immunobiological activities demonstrated for some bacteriophages. This work requires highly purified preparations of the individual phage structural proteins, possessing native conformation that is essential for their reactivity, and free of incompatible biologically active substances such as bacterial lipopolysaccharide (LPS. In this study we describe expression in E. coli and purification of four proteins forming the surface of the bacteriophage T4 head: gp23, gp24, gphoc and gpsoc. We optimized protein expression using a set of chaperones for effective production of soluble proteins in their native conformations. The assistance of chaperones was critical for production of soluble gp23 (chaperone gp31 of T4 phage and of gpsoc (chaperone TF of E. coli. Phage head proteins were purified in native conditions by affinity chromatography and size-exclusion chromatography. Two-step LPS removal allowed immunological purity grade with the average endotoxin activity less than 1 unit per ml of protein preparation. The secondary structure and stability of the proteins were studied using circular dichroism (CD spectrometry, which confirmed that highly purified proteins preserve their native conformations. In increasing concentration of a denaturant (guanidine hydrochloride, protein stability was proved to increase as follows: gpsoc, gp23, gphoc. The denaturation profile of gp24 protein showed independent domain unfolding with the most stable larger domain. The native purified recombinant phage proteins obtained in this work were shown to be suitable for immunological experiments in vivo and in vitro.

  16. Quantifying BSE control by calculating the basic reproduction ratio R0 for the infection among cattle

    NARCIS (Netherlands)

    Koeijer, de A.A.; Heesterbeek, H.; Schreuder, B.E.C.; Oberthur, R.; Wilesmith, J.; Roermund, van H.J.W.; Jong, de M.C.M.

    2004-01-01

    The safety of using meat and bone meal (MBM) in mammal feed was studied in view of BSE, by quantifying the risk of BSE transmission through different infection routes. This risk is embodied in the basic reproduction ratio R(0) of the infection, i.e. the average number of new infections induced by on

  17. Quantifying BSE control by calculating the basic reproduction ratio R0 for the infection among cattle

    NARCIS (Netherlands)

    Koeijer, A. de; Heesterbeek, J.A.P.; Schreuder, B.; Oberthür, R.; Wilesmith, J.; Roermund, H. van; Jong, Mart de

    2004-01-01

    The safety of using meat and bone meal (MBM) in mammal feed was studied in view of BSE, by quantifying the risk of BSE transmission through different infection routes. This risk is embodied in the basic reproduction ratio R 0 of the infection, i.e. the average number of new infections induced by one

  18. Vector-borne diseases: the basic reproduction number R0 and risk maps

    NARCIS (Netherlands)

    Hartemink, N.A.

    2009-01-01

    This thesis deals with the derivation of the basic reproduction number (R0) for vector-borne diseases, in the context of studying the effect of climate change on the risk of emergence diseases. Vector-borne diseases are transmitted from an infected individual to another individual by vectors, usuall

  19. Vanillin and isovanillin: Comparative vibrational spectroscopic studies, conformational stability and NLO properties by density functional theory calculations

    Science.gov (United States)

    Balachandran, V.; Parimala, K.

    This study is a comparative analysis of FT-IR and FT-Raman spectra of vanillin (3-methoxy-4-hydroxybenzaldehyde) and isovanillin (3-hydroxy-4-methoxybenzaldehyde). The molecular structure, vibrational wavenumbers, infrared intensities, Raman scattering activities were calculated for both molecules using the B3LYP density functional theory (DFT) with the standard 6-311++G∗∗ basis set. The computed values of frequencies are scaled using multiple scaling factors to yield good coherence with the observed values. The calculated harmonic vibrational frequencies are compared with experimental FT-IR and FT-Raman spectra. The geometrical parameters and total energies of vanillin and isovanillin were obtained for all the eight conformers (a-h) from DFT/B3LYP method with 6-311++G∗∗ basis set. The computational results identified the most stable conformer of vanillin and isovanillin as in the "a" form. Non-linear properties such as electric dipole moment (μ), polarizability (α), and hyperpolarizability (β) values of the investigated molecules have been computed using B3LYP quantum chemical calculation. The calculated HOMO and LUMO energies show that charge transfer occurs within the molecules.

  20. The conformation effect of the diamine bridge on the stability of dinuclear platinum(II) complexes and their hydrolysis.

    Science.gov (United States)

    Esteves, Lucas F; Dos Santos, Hélio F; Costa, Luiz Antônio S

    2015-09-01

    In this paper, the hydrolysis process of a bisplatinum complex containing the flexible chain 1,6-hexanediamine between the two metal centers was investigated through the use of density functional theory (DFT) with the analysis of the role of the spacing group arrangement on the values of free energy activation barrier. All structures were fully optimized in aqueous solution using implicit model for solvent at DFT level. The energy profiles for the hydrolysis reaction were determined by using the supermolecule approach. Five transition states were proposed differing by the conformation of the bridge group, and the activation free energy calculated as a weighted average within the selected forms. The Gibbs population for reactant was used as a statistical weight leading to the predicted value of 23.1kcalmol(-1), in good accordance with experiment, 23.8kcalmol(-1). Our results suggests that for 1,6-hexanediamine bridge ligand, the extend forms with average torsional angle over the carbon chain larger than 130° have the greatest contribution to the hydrolysis kinetics. The results presented here point out that the hydrolysis mechanism might follow different paths for each conformation and each of these contributes to the observed energy barrier.

  1. Mutation of the His ligand in mitoNEET stabilizes the 2Fe–2S cluster despite conformational heterogeneity in the ligand environment

    Energy Technology Data Exchange (ETDEWEB)

    Conlan, Andrea R.; Paddock, Mark L.; Homer, Christina [University of California at San Diego, La Jolla, CA 92093 (United States); Axelrod, Herbert L.; Cohen, Aina E. [Stanford Synchrotron Radiation Laboratory, 2575 Sand Hill Road, Menlo Park, CA 94025 (United States); Abresch, Edward C.; Zuris, John A. [University of California at San Diego, La Jolla, CA 92093 (United States); Nechushtai, Rachel [Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat Ram, Jerusalem 91904 (Israel); Jennings, Patricia A., E-mail: pajennin@ucsd.edu [University of California at San Diego, La Jolla, CA 92093 (United States)

    2011-06-01

    The spectroscopic and stability properties and X-ray crystal structure of the H87C mutant of the 2Fe–2S ligand mitoNEET are reported. Strikingly, the single point mutation leads to changes in its absorbance and CD spectra and an increase of around sixfold in the stability of the 2Fe–2S clusters over the pH range 5–7. However, the crystal structure of the H87C mutant displays heterogeneity in a few key residues, including the introduced cysteine ligand. Nonetheless, the cluster is highly stabilized from release. MitoNEET is the only identified Fe–S protein localized to the outer mitochondrial membrane and a 1.5 Å resolution X-ray analysis has revealed a unique structure [Paddock et al. (2007 ▶), Proc. Natl Acad. Sci. USA, 104, 14342–14347]. The 2Fe–2S cluster is bound with a 3Cys–1His coordination which defines a new class of 2Fe–2S proteins. The hallmark feature of this class is the single noncysteine ligand His87, which when replaced by Cys decreases the redox potential (E{sub m}) by ∼300 mV and increases the stability of the cluster by around sixfold. Unexpectedly, the pH dependence of the lifetime of the 2Fe–2S cluster remains the same as in the wild-type protein. Here, the crystal structure of H87C mitoNEET was determined to 1.7 Å resolution (R factor = 18%) to investigate the structural basis of the changes in the properties of the 2Fe–2S cluster. In comparison to the wild type, structural changes are localized to the immediate vicinity of the cluster-binding region. Despite the increased stability, Cys87 displays two distinct conformations, with distances of 2.3 and 3.2 Å between the S{sup γ} and the outer Fe of the 2Fe–2S cluster. In addition, Lys55 exhibits multiple conformations in the H87C mutant protein. The structure and distinct characteristics of the H87C mutant provide a framework for further studies investigating the effects of mutation on the properties of the 2Fe–2S cluster in this new class of proteins.

  2. Conserved tertiary couplings stabilize elements in the PDZ fold, leading to characteristic patterns of domain conformational flexibility.

    Science.gov (United States)

    Ho, Bosco K; Agard, David A

    2010-03-01

    Single-domain allostery has been postulated to occur through intramolecular pathways of signaling within a protein structure. We had previously investigated these pathways by introducing a local thermal perturbation and analyzed the anisotropic propagation of structural changes throughout the protein. Here, we develop an improved approach, the Rotamerically Induced Perturbation (RIP), that identifies strong couplings between residues by analyzing the pathways of heat-flow resulting from thermal excitation of rotameric rotations at individual residues. To explore the nature of these couplings, we calculate the complete coupling maps of 5 different PDZ domains. Although the PDZ domain is a well conserved structural fold that serves as a scaffold in many protein-protein complexes, different PDZ domains display unique patterns of conformational flexibility in response to ligand binding: some show a significant shift in a set of alpha-helices, while others do not. Analysis of the coupling maps suggests a simple relationship between the computed couplings and observed conformational flexibility. In domains where the alpha-helices are rigid, we find couplings of the alpha-helices to the body of the protein, whereas in domains having ligand-responsive alpha-helices, no couplings are found. This leads to a model where the alpha-helices are intrinsically dynamic but can be damped if sidechains interact at key tertiary contacts. These tertiary contacts correlate to high covariation contacts as identified by the statistical coupling analysis method. As these dynamic modules are exploited by various allosteric mechanisms, these tertiary contacts have been conserved by evolution.

  3. Comparing methods for estimating R0 from the size distribution of subcritical transmission chains.

    Science.gov (United States)

    Blumberg, S; Lloyd-Smith, J O

    2013-09-01

    Many diseases exhibit subcritical transmission (i.e. 0distribution that permits a variable degree of transmission heterogeneity, we present a unified analysis of existing R0 estimation methods. Simulation studies show that the degree of transmission heterogeneity, when improperly modeled, can significantly impact the bias of R0 estimation methods designed for imperfect observation. These studies also highlight the importance of isolated cases in assessing whether an estimation technique is consistent with observed data. Analysis of data from measles outbreaks shows that likelihood scores are highest for models that allow a flexible degree of transmission heterogeneity. Aggregating intermediate sized chains often has similar performance to analyzing a complete chain size distribution. However, truncating isolated cases is beneficial only when surveillance systems clearly favor full observation of large chains but not small chains. Meanwhile, if data on the type and proportion of cases that are unobserved were known, we demonstrate that maximum likelihood inference of R0 could be adjusted accordingly. This motivates the need for future empirical and theoretical work to quantify observation error and incorporate relevant mechanisms into stuttering chain models used to estimate transmission parameters.

  4. Simulation of infrared spectra for beta-hairpin peptides stabilized by an Aib-Gly turn sequence: correlation between conformational fluctuation and vibrational coupling.

    Science.gov (United States)

    Kim, Joohyun; Huang, Rong; Kubelka, Jan; Bou Rcaron, Petr; Keiderling, Timothy A

    2006-11-23

    Vibrational spectra of a 12-residue beta-hairpin peptide, RYVEVBGKKILQ (HBG), stabilized by an Aib-Gly turn sequence (B = Aib) were investigated theoretically using a combination of molecular dynamics (MD) and density functional theory (DFT) calculations. Selected conformations of HBG were extracted from a classical MD trajectory and used for spectral simulations. DFT calculations, based on the Cartesian coordinate spectral property transfer protocol, were carried out for peptide structures in which all residues are replaced with Ala, except for the Aib and Gly residues, but the backbone (phi, psi, omega) structure of the original configuration is retained. The simulations provide a basis for interpretation of the HBG amide I infrared spectra in terms of structural variables such as detailed secondary structure and thermal conformational fluctuation as well as vibrational coupling as indicated by spectra of 13C isotope-labeled variants. The characteristic amide I band shape of such small beta-hairpin peptides appears to arise from the structure of the short antiparallel beta-sheet strands. The role of structural parameter fluctuation in vibrational coupling is evaluated by comparison of DFT-derived amide coupling constants for selected configurations and from transition dipole coupling calculations of coupling parameters between (13)C isotopically labeled residues for a MD-derived ensemble of configurations. Calculated results were compared with the experimentally obtained spectra for several (13)C isotope-labeled peptides of this sequence.

  5. Fecal Excretion of Orally Administered Collagen-Like Peptides in Rats: Contribution of the Triple-Helical Conformation to Their Stability.

    Science.gov (United States)

    Koide, Takaki; Yamamoto, Naoyuki; Taira, Kazuma B; Yasui, Hiroyuki

    2016-01-01

    Orally ingested peptides are generally digested in the gastrointestinal (GI) tract and absorbed in the form of oligopeptides. We previously reported that intravenously administered collagen-like triple-helical peptides circulated in the bloodstream and were excreted in their intact forms in urine nearly quantitatively. In the present study, we investigated the fates of orally administered collagen-like peptides in rats. (Pro-Hyp-Gly)10 (Hyp: 4-hydroxyproline), which formed a stable triple-helical structure, was stable in the GI tract, and 72.3±13.0% of the peptide was excreted in the feces. Its recovery ratio was similar to that of all-D-(Pro-Pro-Gly)10 (75.1±15.7%), the indigestible control. In contrast, (Pro-Hyp-Gly)5 and (Pro-Pro-Gly)10, the random coil conformations of which were dominant at body temperature, were not detected in fecal samples, indicating that they were digested by proteases. The high stability of the triple-helical conformation in mammalian bodies suggests the potential use of collagen-like peptides as novel scaffolds of peptide drugs.

  6. Conformational stability, molecular orbital studies (chemical hardness and potential), vibrational investigation and theoretical NBO analysis of 4-tert-butyl-3-methoxy-2,6-dinitrotoluene.

    Science.gov (United States)

    Saravanan, S; Balachandran, V; Vishwanathan, K

    2014-04-24

    The FT-IR and FT-Raman spectra of 4-tert-butyl-3-methoxy-2,6-dinitrotoluene (musk ambrette) have been recorded in the regions 4000-400 cm(-1) and 3500-100 cm(-1), respectively. The total energy calculations of musk ambrette were tried for the possible conformers. The molecular structure, geometry optimization, vibrational frequencies were obtained by the density functional theory (DFT) using B3LYP and LSDA method with 6-311G(d,p) basis set for the most stable conformer "C1". The complete assignments were performed on the basis of the potential energy distribution (PED) of the vibrational modes, calculated and the scaled values were compared with experimental FT-IR and FT-Raman spectra. The observed and the calculated frequencies are found to be in good agreement. The stability of the molecule arising from hyper conjugate interactions and the charge delocalization has been analyzed using bond orbital (NBO) analysis. The HOMO and LUMO energy gap reveals that the energy gap reflects the chemical activity of the molecule. The dipole moment (μ), polarizability (α), anisotropy polarizability (Δα) and first hyperpolarizability (βtot) of the molecule have been reported. The thermodynamic functions (heat capacity, entropy and enthalpy) were obtained for the range of temperature 100-1000 K. Information about the size, shape, charge density distribution and site of chemical reactivity of the molecule has been obtained by mapping electron density isosurface with molecular electrostatic potential (MEP).

  7. Effect of polyethylene glycol conjugation on conformational and colloidal stability of a monoclonal antibody antigen-binding fragment (Fab').

    Science.gov (United States)

    Roque, Cristopher; Sheung, Anthony; Rahman, Nausheen; Ausar, S Fernando

    2015-02-01

    We have investigated the effects of site specific "hinge" polyethylene glycol conjugation (PEGylation) on thermal, pH, and colloidal stability of a monoclonal antibody antigen-binding fragment (Fab') using a variety of biophysical techniques. The results obtained by circular dichroism (CD), ultraviolet (UV) absorbance, and fluorescence spectroscopy suggested that the physical stability of the Fab' is maximized at pH 6-7 with no apparent differences due to PEGylation. Temperature-induced aggregation experiments revealed that PEGylation was able to increase the transition temperature, as well as prevent the formation of visible and subvisible aggregates. Statistical comparison of the three-index empirical phase diagram (EPD) revealed significant differences in thermal and pH stability signatures between Fab' and PEG-Fab'. Upon mechanical stress, micro-flow imaging (MFI) and measurement of the optical density at 360 nm showed that the PEG-Fab' had significantly higher resistance to surface-induced aggregation compared to the Fab'. Analysis of the interaction parameter, kD, indicated repulsive intermolecular forces for PEG-Fab' and attractive forces for Fab'. In conclusion, PEGylation appears to protect Fab' against thermal and mechanical stress-induced aggregation, likely due to a steric hindrance mechanism.

  8. Conformal Nets II: Conformal Blocks

    Science.gov (United States)

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

    2017-03-01

    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.

  9. 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.

  10. Dynamique des populations : Histoire de $R_0$, de Fibonacci à la grippe H1N1

    OpenAIRE

    Bacaër, Nicolas

    2009-01-01

    International audience; En ces temps de grippe, les modélisateurs sont particulièrement sollicités pour essayer de prévoir l'évolution de l'épidémie ou l'effet que pourraient avoir certaines interventions comme la fermeture d'écoles, la restriction des voyages, une campagne de vaccination, etc. Dans le discours de ces apprentis futurologues revient souvent un paramètre connu sous le nom de $R_0$ (prononcer R-zéro) et qui représente grosso modo le nombre de cas secondaires qu'un malade peut in...

  11. Subalgebras of R0-Algebra [0,1] and Generalized Tautology%R0-代数[0,1]的子代数与广义重言式

    Institute of Scientific and Technical Information of China (English)

    王龙春; 王国俊

    2004-01-01

    本文是对修正的Kleene系统中广义重言式理论的推广,讨论了R0-代数[0,1]的各类无限子R0-代数中的广义重言式,证明了在子R0-代数E2中,(* )*中存在着可数多个不同的广义重言式.

  12. Glu311 and Arg337 Stabilize a Closed Active-site Conformation and Provide a Critical Catalytic Base and Countercation for Green Bioluminescence in Beetle Luciferases.

    Science.gov (United States)

    Viviani, V R; Simões, A; Bevilaqua, V R; Gabriel, G V M; Arnoldi, F G C; Hirano, T

    2016-08-30

    Beetle luciferases elicit the emission of different bioluminescence colors from green to red. Whereas firefly luciferases emit yellow-green light and are pH-sensitive, undergoing a typical red-shift at acidic pH and higher temperatures and in the presence of divalent heavy metals, click beetle and railroadworm luciferases emit a wider range of colors from green to red but are pH-independent. Despite many decades of study, the structural determinants and mechanisms of bioluminescence colors and pH sensitivity remain enigmatic. Here, through modeling studies, site-directed mutagenesis, and spectral and kinetic studies using recombinant luciferases from the three main families of bioluminescent beetles that emit different colors of light (Macrolampis sp2 firefly, Phrixotrix hirtus railroadworm, and Pyrearinus termitilluminans click beetle), we investigated the role of E311 and R337 in bioluminescence color determination. All mutations of these residues in firefly luciferase produced red mutants, indicating that the preservation of opposite charges and the lengths of the side chains of E311 and R337 are essential for keeping a salt bridge that stabilizes a closed hydrophobic conformation favorable for green light emission. Kinetic studies indicate that residue R337 is important for binding luciferin and creating a positively charged environment around excited oxyluciferin phenolate. In Pyrearinus green-emitting luciferase, the R334A mutation causes a 27 nm red-shift, whereas in Phrixotrix red-emitting luciferase, the L334R mutation causes a blue-shift that is no longer affected by guanidine. These results provide compelling evidence that the presence of arginine at position 334 is essential for blue-shifting the emission spectra of most beetle luciferases. Therefore, residues E311 and R337 play both structural and catalytic roles in bioluminescence color determination, by stabilizing a closed hydrophobic conformation favorable for green light emission, and also

  13. Heat, Acid and Chemically Induced Unfolding Pathways, Conformational Stability and Structure-Function Relationship in Wheat α-Amylase.

    Directory of Open Access Journals (Sweden)

    Kritika Singh

    Full Text Available Wheat α-amylase, a multi-domain protein with immense industrial applications, belongs to α+β class of proteins with native molecular mass of 32 kDa. In the present study, the pathways leading to denaturation and the relevant unfolded states of this multi-domain, robust enzyme from wheat were discerned under the influence of temperature, pH and chemical denaturants. The structural and functional aspects along with thermodynamic parameters for α-amylase unfolding were probed and analyzed using fluorescence, circular dichroism and enzyme assay methods. The enzyme exhibited remarkable stability up to 70°C with tendency to aggregate at higher temperature. Acid induced unfolding was also incomplete with respect to the structural content of the enzyme. Strong ANS binding at pH 2.0 suggested the existence of a partially unfolded intermediate state. The enzyme was structurally and functionally stable in the pH range 4.0-9.0 with 88% recovery of hydrolytic activity. Careful examination of biophysical properties of intermediate states populated in urea and GdHCl induced denaturation suggests that α-amylase unfolding undergoes irreversible and non-coincidental cooperative transitions, as opposed to previous reports of two-state unfolding. Our investigation highlights several structural features of the enzyme in relation to its catalytic activity. Since, α-amylase has been comprehensively exploited for use in a range of starch-based industries, in addition to its physiological significance in plants and animals, knowledge regarding its stability and folding aspects will promote its biotechnological applications.

  14. Heat, Acid and Chemically Induced Unfolding Pathways, Conformational Stability and Structure-Function Relationship in Wheat α-Amylase.

    Science.gov (United States)

    Singh, Kritika; Shandilya, Manish; Kundu, Suman; Kayastha, Arvind M

    2015-01-01

    Wheat α-amylase, a multi-domain protein with immense industrial applications, belongs to α+β class of proteins with native molecular mass of 32 kDa. In the present study, the pathways leading to denaturation and the relevant unfolded states of this multi-domain, robust enzyme from wheat were discerned under the influence of temperature, pH and chemical denaturants. The structural and functional aspects along with thermodynamic parameters for α-amylase unfolding were probed and analyzed using fluorescence, circular dichroism and enzyme assay methods. The enzyme exhibited remarkable stability up to 70°C with tendency to aggregate at higher temperature. Acid induced unfolding was also incomplete with respect to the structural content of the enzyme. Strong ANS binding at pH 2.0 suggested the existence of a partially unfolded intermediate state. The enzyme was structurally and functionally stable in the pH range 4.0-9.0 with 88% recovery of hydrolytic activity. Careful examination of biophysical properties of intermediate states populated in urea and GdHCl induced denaturation suggests that α-amylase unfolding undergoes irreversible and non-coincidental cooperative transitions, as opposed to previous reports of two-state unfolding. Our investigation highlights several structural features of the enzyme in relation to its catalytic activity. Since, α-amylase has been comprehensively exploited for use in a range of starch-based industries, in addition to its physiological significance in plants and animals, knowledge regarding its stability and folding aspects will promote its biotechnological applications.

  15. Beyond R0: demographic models for variability of lifetime reproductive output.

    Directory of Open Access Journals (Sweden)

    Hal Caswell

    Full Text Available The net reproductive rate R0 measures the expected lifetime reproductive output of an individual, and plays an important role in demography, ecology, evolution, and epidemiology. Well-established methods exist to calculate it from age- or stage-classified demographic data. As an expectation, R0 provides no information on variability; empirical measurements of lifetime reproduction universally show high levels of variability, and often positive skewness among individuals. This is often interpreted as evidence of heterogeneity, and thus of an opportunity for natural selection. However, variability provides evidence of heterogeneity only if it exceeds the level of variability to be expected in a cohort of identical individuals all experiencing the same vital rates. Such comparisons require a way to calculate the statistics of lifetime reproduction from demographic data. Here, a new approach is presented, using the theory of Markov chains with rewards, obtaining all the moments of the distribution of lifetime reproduction. The approach applies to age- or stage-classified models, to constant, periodic, or stochastic environments, and to any kind of reproductive schedule. As examples, I analyze data from six empirical studies, of a variety of animal and plant taxa (nematodes, polychaetes, humans, and several species of perennial plants.

  16. Utility of R0 as a predictor of disease invasion in structured populations

    Science.gov (United States)

    Cross, P.C.; Johnson, P.L.F.; Lloyd-Smith, J. O.; Getz, W.M.

    2007-01-01

    Early theoretical work on disease invasion typically assumed large and well-mixed host populations. Many human and wildlife systems, however, have small groups with limited movement among groups. In these situations, the basic reproductive number, R0, is likely to be a poor predictor of a disease pandemic because it typically does not account for group structure and movement of individuals among groups. We extend recent work by combining the movement of hosts, transmission within groups, recovery from infection and the recruitment of new susceptibles into a stochastic model of disease in a host metapopulation. We focus on how recruitment of susceptibles affects disease invasion and how population structure can affect the frequency of superspreading events (SSEs). We show that the frequency of SSEs may decrease with the reduced movement and the group sizes due to the limited number of susceptible individuals available. Classification tree analysis of the model results illustrates the hierarchical nature of disease invasion in host metapopulations. First, the pathogen must effectively transmit within a group (R0 > 1), and then the pathogen must persist within a group long enough to allow for movement among the groups. Therefore, the factors affecting disease persistence - such as infectious period, group size and recruitment of new susceptibles - are as important as the local transmission rates in predicting the spread of pathogens across a metapopulation. ?? 2006 The Royal Society.

  17. 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...

  18. Deletion of intragenic tandem repeats in unit C of FLO1 of Saccharomyces cerevisiae increases the conformational stability of flocculin under acidic and alkaline conditions.

    Directory of Open Access Journals (Sweden)

    Ee Li

    Full Text Available Flocculation is an attractive property for Saccaromyces cerevisiae, which plays important roles in fermentation industry and environmental remediation. The process of flocculation is mediated by a family of cell surface flocculins. As one member of flocculins, Flo1 is characterized by four families of repeats (designated as repeat units A, B, C and D in the central domain. It is generally accepted that variation of repeat unit A in length in Flo1 influences the degree of flocculation or specificity for sugar recognization. However, no reports were observed for other repeat units. Here, we compared the flocculation ability and its sensitivity to environmental factors between yeast strain YSF1 carrying the intact FLO1 gene and yeast strains carrying the derived forms of FLO1 with partial or complete deletion of repeats in unit C. No obvious differences in flocculation ability and specificity of carbohydrate recognition were observed among these yeast strains, which indicates the truncated flocculins can stride across the cell wall and cluster the N-terminal domain on the surface of yeast cells as the intact Flo1 thereby improving intercellular binding. However, yeast strains with the truncated flocculins required more mannose to inhibit completely the flocculation, displayed broad tolerance of flocculation to pH fluctuation, and the fewer the repeats in unit C, the stronger adaptability of flocculation to pH change, which was not relevant to the position of deletion. This suggests that more stable active conformation is obtained for flocculin by deletion the repeat unit C in the central domain of Flo1, which was validated further by the higher hydrophobicity on the surface of cells of YSF1c with complete deletion of unit C under neutral and alkaline conditions and the stabilization of GFP conformation by fusion with flocculin with complete deletion of unit C in the central domain.

  19. Conformal Gravity Rotation Curves with a Conformal Higgs Halo

    CERN Document Server

    Horne, Keith

    2016-01-01

    We discuss the effect of a conformally coupled Higgs field on conformal gravity (CG) predictions for the rotation curves of galaxies. The Mannheim-Kazanas (MK) metric is a valid vacuum solution of CG's 4-th order Poisson equation only if the Higgs field has a particular radial profile, S(r)=S_0 a/(r+a), decreasing from S_0 at r=0 with radial scale length a. Since particle rest masses scale with S(r)/S_0, their world lines do not follow time-like geodesics of the MK metric g_{\\mu\

  20. Association thermodynamics and conformational stability of beta-sheet amyloid beta(17-42) oligomers: effects of E22Q (Dutch) mutation and charge neutralization.

    Science.gov (United States)

    Blinov, Nikolay; Dorosh, Lyudmyla; Wishart, David; Kovalenko, Andriy

    2010-01-20

    Amyloid fibrils are associated with many neurodegenerative diseases. It was found that amyloidogenic oligomers, not mature fibrils, are neurotoxic agents related to these diseases. Molecular mechanisms of infectivity, pathways of aggregation, and molecular structure of these oligomers remain elusive. Here, we use all-atom molecular dynamics, molecular mechanics combined with solvation analysis by statistical-mechanical, three-dimensional molecular theory of solvation (also known as 3D-RISM-KH) in a new MM-3D-RISM-KH method to study conformational stability, and association thermodynamics of small wild-type Abeta(17-42) oligomers with different protonation states of Glu(22), as well the E22Q (Dutch) mutants. The association free energy of small beta-sheet oligomers shows near-linear trend with the dimers being thermodynamically more stable relative to the larger constructs. The linear (within statistical uncertainty) dependence of the association free energy on complex size is a consequence of the unilateral stacking of monomers in the beta-sheet oligomers. The charge reduction of the wild-type Abeta(17-42) oligomers upon protonation of the solvent-exposed Glu(22) at acidic conditions results in lowering the association free energy compared to the wild-type oligomers at neutral pH and the E22Q mutants. The neutralization of the peptides because of the E22Q mutation only marginally affects the association free energy, with the reduction of the direct electrostatic interactions mostly compensated by the unfavorable electrostatic solvation effects. For the wild-type oligomers at acidic conditions such compensation is not complete, and the electrostatic interactions, along with the gas-phase nonpolar energetic and the overall entropic effects, contribute to the lowering of the association free energy. The differences in the association thermodynamics between the wild-type Abeta(17-42) oligomers at neutral pH and the Dutch mutants, on the one hand, and the Abeta(17

  1. Human serum albumin as protecting agent of silver nanoparticles: role of the protein conformation and amine groups in the nanoparticle stabilization

    Energy Technology Data Exchange (ETDEWEB)

    Alarcon, Emilio I.; Bueno-Alejo, Carlos J.; Noel, Christopher W.; Stamplecoskie, Kevin G. [Centre for Catalysis Research and Innovation, University of Ottawa, Department of Chemistry (Canada); Pacioni, Natalia L. [Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, INFIQC, Departamento de Quimica Organica (Argentina); Poblete, Horacio [Center for Bioinformatics and Molecular Simulations, Universidad de Talca (Chile); Scaiano, J. C., E-mail: tito@photo.chem.uottawa.ca [Centre for Catalysis Research and Innovation, University of Ottawa, Department of Chemistry (Canada)

    2013-01-15

    Thermally denatured human serum albumin interacts with {approx}3.0 nm spherical AgNP enhancing the fluorescence of Trp-214 at large protein/nanoparticle ratios. However, using native HSA, no changes in the emission were observed. The observation is likely due to differences between native and denatured protein packing resulting from protein corona formation. We have also found that NH{sub 2} blocking of the protein strongly affects the ability of the protein to protect AgNP from different salts/ions such as NaCl, PBS, Hank's buffer, Tris-HCl, MES, and DMEM. Additionally, AgNP can be readily prepared in aqueous solutions by a photochemical approach employing HSA as an in situ protecting agent. The role of the protein in this case is beyond that of protecting agent; thus, Ag{sup +} ions and I-2959 complexation within the protein structure also affects the efficiency of AgNP formation. Blocking NH{sub 2} in HSA modified the AgNP growth profile, surface plasmon band shape, and long-term stability suggesting that amine groups are directly involved in the formation and post-stabilization of AgNP. In particular, AgNP size and shape are extensively influenced by NH{sub 2} blocking, leading primarily to cubes and plates with sizes around 5-15 nm; in contrast, spherical monodisperse 4.0 nm AgNP are observed for native HSA. The nanoparticles prepared by this protocol are non-toxic in primary cells and have remarkable antibacterial properties. Finally, surface plasmon excitation of native HSA-AgNP promoted loss of protein conformation in just 5 min, suggesting that plasmon heating causes protein denaturation using continuous light sources such as commercial LED.

  2. Insight into the conformational stability of membrane-embedded BamA using a combined solution and solid-state NMR approach

    Energy Technology Data Exchange (ETDEWEB)

    Sinnige, Tessa; Houben, Klaartje [Utrecht University, NMR Spectroscopy, Department of Chemistry, Faculty of Science, Bijvoet Center for Biomolecular Research (Netherlands); Pritisanac, Iva [Physical and Theoretical Chemistry Laboratory (United Kingdom); Renault, Marie [Institute of Pharmacology and Structural Biology (France); Boelens, Rolf; Baldus, Marc, E-mail: m.baldus@uu.nl [Utrecht University, NMR Spectroscopy, Department of Chemistry, Faculty of Science, Bijvoet Center for Biomolecular Research (Netherlands)

    2015-04-15

    The β-barrel assembly machinery (BAM) is involved in folding and insertion of outer membrane proteins in Gram-negative bacteria, a process that is still poorly understood. With its 790 residues, BamA presents a challenge to current NMR methods. We utilized a “divide and conquer” approach in which we first obtained resonance assignments for BamA’s periplasmic POTRA domains 4 and 5 by solution NMR. Comparison of these assignments to solid-state NMR (ssNMR) data obtained on two BamA constructs including the transmembrane domain and one or two soluble POTRA domains suggested that the fold of POTRA domain 5 critically depends on the interface with POTRA 4. Using specific labeling schemes we furthermore obtained ssNMR resonance assignments for residues in the extracellular loop 6 that is known to be crucial for BamA-mediated substrate folding and insertion. Taken together, our data provide novel insights into the conformational stability of membrane-embedded, non-crystalline BamA.

  3. The Combined Repetitive Oligopeptides of Clostridium difficile Toxin A Counteract Premature Cleavage of the Glucosyl-Transferase Domain by Stabilizing Protein Conformation

    Directory of Open Access Journals (Sweden)

    Alexandra Olling

    2014-07-01

    Full Text Available Toxin A (TcdA and B (TcdB from Clostridium difficile enter host cells by receptor-mediated endocytosis. A prerequisite for proper toxin action is the intracellular release of the glucosyltransferase domain by an inherent cysteine protease, which is allosterically activated by inositol hexaphosphate (IP6. We found that in in vitro assays, the C-terminally-truncated TcdA1–1065 was more efficient at IP6-induced cleavage compared with full-length TcdA. We hypothesized that the C-terminally-located combined repetitive oligopeptides (CROPs interact with the N-terminal part of the toxin, thereby preventing autoproteolysis. Glutathione-S-transferase (GST pull-down assays and microscale thermophoresis confirmed binding between the CROPs and the glucosyltransferase (TcdA1–542 or intermediate (TcdA1102–1847 domain of TcdA, respectively. This interaction between the N- and C-terminus was not found for TcdB. Functional assays revealed that TcdB was more susceptible to inactivation by extracellular IP6-induced cleavage. In vitro autoprocessing and inactivation of TcdA, however, significantly increased, either by acidification of the surrounding milieu or following exchange of its CROP domain by the homologous CROP domain of TcdB. Thus, TcdA CROPs contribute to the stabilization and protection of toxin conformation in addition to function as the main receptor binding domain.

  4. The common hereditary elliptocytosis-associated α-spectrin L260P mutation perturbs erythrocyte membranes by stabilizing spectrin in the closed dimer conformation.

    Science.gov (United States)

    Harper, Sandra L; Sriswasdi, Sira; Tang, Hsin-Yao; Gaetani, Massimiliano; Gallagher, Patrick G; Speicher, David W

    2013-10-24

    Hereditary elliptocytosis (HE) and hereditary pyropoikilocytosis (HPP) are common disorders of erythrocyte shape primarily because of mutations in spectrin. The most common HE/HPP mutations are located distant from the critical αβ-spectrin tetramerization site, yet still interfere with formation of spectrin tetramers and destabilize the membrane by unknown mechanisms. To address this question, we studied the common HE-associated mutation, αL260P, in the context of a fully functional mini-spectrin. The mutation exhibited wild-type tetramer binding in univalent binding assays, but reduced binding affinity in bivalent-binding assays. Biophysical analyses demonstrated the mutation-containing domain was only modestly structurally destabilized and helical content was not significantly changed. Gel filtration analysis of the αL260P mini-spectrin indicated more compact structures for dimers and tetramers compared with wild-type. Chemical crosslinking showed structural changes in the mutant mini-spectrin dimer were primarily restricted to the vicinity of the αL260P mutation and indicated large conformational rearrangements of this region. These data indicate the mutation increased the stability of the closed dimer state, thereby reducing tetramer assembly and resulting in membrane destabilization. These results reveal a novel mechanism of erythrocyte membrane destabilization that could contribute to development of therapeutic interventions for mutations in membrane proteins containing spectrin-type domains associated with inherited disease.

  5. Conformational stability, spectroscopic (FT-IR, FT-Raman and UV-Vis) analysis, NLO, NBO, FMO and Fukui function analysis of 4-hexylacetophenone by density functional theory.

    Science.gov (United States)

    Saravanan, S; Balachandran, V

    2015-03-05

    The experimental and theoretical study on the structures and vibrations of 4-hexylacetophenone (abbreviated as 4HAP) are presented. The FT-IR and FT-Raman spectra of the title compound have been recorded in the region 4000-400cm(-1) and 3500-100cm(-1) respectively. The molecular structures, vibrational wavenumbers, infrared intensities and Raman activities were calculated using DFT (B3LYP and LSDA) method with 6-311++G(d,p) basis set. The most stable conformer of 4HAP is identified from the computational results. The assignments of the vibrational spectra have been carried out with the aid of normal coordinate analysis (NCA) following the scaled quantum mechanical force field methodology (SQMEF). The linear polarizability (α) and the first hyperpolarizability (βtot) values of the investigated molecule have been computed using B3LYP and LSDA with 6-311++G(d,p) basis set. Stability of the molecule arising from hyper conjugative interaction and charge transfer delocalization has been analyzed using natural bond orbital (NBO) analysis. The molecule orbital contributions are studied by density of energy states (DOSs). UV-Vis spectrum and effects of solvents have been discussed effects of solvents have been discussed and the electronic properties such as HOMO and LUMO energies were determined by time-dependent TD-DFT approach. Fukui function and Mulliken analysis on atomic charges of the title compound have been calculated. Finally, electrophilic and nucleophilic descriptors of the title molecule have been calculated.

  6. Infrared and Raman spectra, adjusted r0 structural parameters, and vibrational assignment of isopropyl isocyanide

    Science.gov (United States)

    Sawant, Dattatray K.; Klaassen, Joshua J.; Panikar, Savitha S.; Durig, James R.

    2014-09-01

    Infrared spectra (3200-220 cm-1) of gaseous and Raman spectra (3200-40 cm-1) of liquid isopropyl isocyanide ((CH3)2CHNC) have been recorded. By utilizing the microwave rotational constants combined with the structural parameters predicted from MP2(full)/6-311+G(d,p) calculations, adjusted r0 parameters have been obtained for isopropyl isocyanide. The heavy atom distances in Å are: r (C1tbnd N2) = 1.176(3), r (N2sbnd C3) = 1.437(3), r (C3sbnd C4,5) = 1.525(5) and the angles in (°) are ∠C1N2C3 = 178.6(5); ∠N2C3C4,5 = 109.4(5); ∠C4C3C5 = 113.0(5). A complete vibrational assignment is proposed for isopropyl isocyanide based on infrared band contours, relative intensities, depolarization values, and group frequencies. The vibrational assignments were supported by normal coordinate calculation utilizing the force constants from ab inito MP2(full)/6-31G(d). The results are discussed and compared to those obtained for some similar molecules.

  7. 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

  8. Ethanol Dimer: Observation of Three New Conformers by Broadband Rotational Spectroscopy

    Science.gov (United States)

    Loru, Donatella; Peña, Isabel; Sanz, M. Eugenia

    2017-06-01

    The conformational behaviour of the hydrogen-bonded cluster ethanol dimer has been reinvestigated by chirped pulse Fourier transform microwave spectroscopy in the 2-8 GHz frequency region. Three new conformers ({tt}, {tg}+, and {g}-{g}+) have been identified together with the three ({g}+{g}+, {g}-{t}, and {g}+{t}) previously observed by Hearn et al. (J. Chem. Phys. 123, 134324, 2005) and their rotational and centrifugal distortion constants have been determined. By using different carrier gases in the supersonic expansion, the relative abundances of the observed conformers have been estimated. The monosubstituted ^{13}C species and some of the ^{18}O species of the most abundant conformers {g}+{g}+, {g}-{t}, and {tt} have been observed in their natural abundance, which led to the partial determination of their r_{s} structures, and the r_{0} structure for the {tt} conformer. The six observed conformers are stabilized by the delicate interplay of primary O-H...O and secondary C-H...O hydrogen bonds, and dispersion interactions between the methyl groups. Density functional and ab initio methods with different basis sets are benchmarked against the experimental data.

  9. Workers’ Conformism

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    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.

  10. Leu85 in the beta1-beta2 linker of ASIC1 slows activation and decreases the apparent proton affinity by stabilizing a closed conformation.

    Science.gov (United States)

    Li, Tianbo; Yang, Youshan; Canessa, Cecilia M

    2010-07-16

    Acid-sensing ion channels (ASICs) are proton-activated channels expressed in neurons of the central and peripheral nervous systems where they modulate neuronal activity in response to external increases in proton concentration. The size of ASIC1 currents evoked by a given local acidification is determined by the number of channels in the plasma membrane and by the apparent proton affinities for activation and steady-state desensitization of the channel. Thus, the magnitude of the pH drop and the value of the baseline pH both are functionally important. Recent characterization of ASIC1s from an increasing number of species has made evident that proton affinities of these channels vary across vertebrates. We found that in species with high baseline plasma pH, e.g. frog, shark, and fish, ASIC1 has high proton affinity compared with the mammalian channel. The beta1-beta2 linker in the extracellular domain, specifically by the substitution M85L, determines the interspecies differences in proton affinities and also the time course of ASIC1 macroscopic currents. The mechanism underlying these observations is a delay in channel opening after application of protons, most likely by stabilizing a closed conformation that decreases the apparent affinity to protons and also slows the rise and decay phases of the current. Together, the results suggest evolutionary adaptation of ASIC1 to match the value of the species-specific plasma pH. At the molecular level, adaptation is achieved by substitutions of nonionizable residues rather than by modification of the channel proton sensor.

  11. Comparison of the historic recycling risk for BSE in three European countries by calculating the basic reproduction ratio R0.

    Science.gov (United States)

    Schwermer, Heinzpeter; de Koeijer, Aline; Brülisauer, Franz; Heim, Dagmar

    2007-10-01

    A deterministic model of BSE transmission is used to calculate the R(0) values for specific years of the BSE epidemics in the United Kingdom (UK), the Netherlands (NL), and Switzerland (CH). In all three countries, the R(0) values decreased below 1 after the introduction of a ban on feeding meat and bone meal (MBM) to ruminants around the 1990s. A variety of additional measures against BSE led to further decrease of R(0) to about 0.06 in the years around 1998. The calculated R(0) values were consistent with the observations made on the surveillance results for UK, but were partially conflicting with the surveillance results for NL and CH. There was evidence for a dependency of the BSE epidemic in NL and CH from an infection source not considered in the deterministic transmission model. Imports of MBM and feed components can be an explanation for this discrepancy, and the importance of imports for these observations is discussed.

  12. Conformal Infinity

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    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.

  13. Conformal Infinity

    Science.gov (United States)

    Frauendiener, Jörg

    2004-12-01

    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.

  14. 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.

  15. 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.

  16. Conformational stability, vibrational spectra, HOMO-LUMO and NBO analysis of 1,3,4-thiadiazolidine-2,5-dithione with experimental (FT-IR and FT-Raman) techniques and scaled quantum mechanical calculations.

    Science.gov (United States)

    Xavier, R John; Dinesh, P

    2013-09-01

    The experimental and theoretical study on the structure and vibrations of 1,3,4-thiadiazolidine-2,5-dithione (TDZD) is presented. The FT-IR spectra (4000-400 cm(-1)) and the FT-Raman spectra (4000-50 cm(-1)) of the title molecule have been recorded. The energies of TDZD were obtained for all the possible four conformers from HF and DFT with 6-311G(d,p) and 6-311++G(d,p) basis set calculations. From the computational results, conformer C4 is identified as the most stable conformers of TDZD. The spectroscopic and theoretical results are compared with the corresponding properties for TDZD of C4 conformer. The temperature dependence of thermodynamic properties has been analyzed. Molecular stability and bond strength were investigated by applying the natural bond orbital analysis (NBO). The calculated HOMO and LUMO energies show that charge transfer occurs in the molecules. Information about the size, shape, charge density distribution, and site of chemical reactivity of the molecules has been obtained by mapping electron density isosurface with electrostatic potential (ESP). The dipole moment (λ) and polarizability (α), anisotropy polarizability (Δα) and first hyperpolarizability (βtotal) of the molecule have been reported.

  17. 四值非全序R0命题逻辑上的随机伪度量%Randomized pseudo - metric of R0 - type 4 - valued non - totally ordered propositional logic

    Institute of Scientific and Technical Information of China (English)

    左卫兵

    2012-01-01

    通过引入随机化映射和真度权函数等概念,在四值非全序R0命题逻辑系统中提出了公式的可变随机真度,得到可变随机真度的一些基本性质,提出了2公式间的随机相似度和随机伪度量,建立了四值非全序R0命题逻辑系统上的随机逻辑伪度量空间,为在四值非全序命题逻辑系统上进行近似推理提供了一种可能的框架.%By introducing random mapping and truth degree weight function, we define the varialble randomized truth degree of formula in R0 - type 4 - valued non - totally ordered propositional logic system. The basic properties of variable randomized truth degree are obtained in this paper. The concept of randomized similarity and randomized pseudo - metri.c is introduced and randomized logic metric space in R0 - type 4 - valued non - totally ordered propositional logic system is also established, which provides possible framework for approximate reasoning in the logic system of 4 -valued non -totally ordered propositional logic system.

  18. Stabilization

    Directory of Open Access Journals (Sweden)

    Muhammad H. Al-Malack

    2016-07-01

    Full Text Available Fuel oil flyash (FFA produced in power and water desalination plants firing crude oils in the Kingdom of Saudi Arabia is being disposed in landfills, which increases the burden on the environment, therefore, FFA utilization must be encouraged. In the current research, the effect of adding FFA on the engineering properties of two indigenous soils, namely sand and marl, was investigated. FFA was added at concentrations of 5%, 10% and 15% to both soils with and without the addition of Portland cement. Mixtures of the stabilized soils were thoroughly evaluated using compaction, California Bearing Ratio (CBR, unconfined compressive strength (USC and durability tests. Results of these tests indicated that stabilized sand mixtures could not attain the ACI strength requirements. However, marl was found to satisfy the ACI strength requirement when only 5% of FFA was added together with 5% of cement. When the FFA was increased to 10% and 15%, the mixture’s strength was found to decrease to values below the ACI requirements. Results of the Toxicity Characteristics Leaching Procedure (TCLP, which was performed on samples that passed the ACI requirements, indicated that FFA must be cautiously used in soil stabilization.

  19. R0 for vector-borne diseases: impact of the assumption for the duration of the extrinsic incubation period

    NARCIS (Netherlands)

    Hartemink, Nienke; Cianci, Daniela; Reiter, Paul

    2015-01-01

    Mathematical modeling and notably the basic reproduction number R0 have become popular tools for the description of vector-borne disease dynamics. We compare two widely used methods to calculate the probability of a vector to survive the extrinsic incubation period. The two methods are based on diff

  20. R0 for vector-borne diseases : impact of the assumption for the duration of the extrinsic incubation period

    NARCIS (Netherlands)

    Hartemink, N.; Cianci, D.; Reiter, P.

    2015-01-01

    Mathematical modeling and notably the basic reproduction number R0 have become popular tools for the description of vector-borne disease dynamics. We compare two widely used methods to calculate the probability of a vector to survive the extrinsic incubation period. The two methods are based on diff

  1. R0 for vector-borne diseases : impact of the assumption for the duration of the extrinsic incubation period

    NARCIS (Netherlands)

    Hartemink, N.; Cianci, D.; Reiter, P.

    2015-01-01

    Mathematical modeling and notably the basic reproduction number R0 have become popular tools for the description of vector-borne disease dynamics. We compare two widely used methods to calculate the probability of a vector to survive the extrinsic incubation period. The two methods are based on diff

  2. Influence of Transition Metal Cationization versus Sodium Cationization and Protonation on the Gas-Phase Tautomeric Conformations and Stability of Uracil: Application to [Ura+Cu]+ and [Ura+Ag]+

    Science.gov (United States)

    Akinyemi, T. E.; Wu, R. R.; Nei, Y.-W.; Cunningham, N. A.; Roy, H. A.; Steill, J. D.; Berden, G.; Oomens, J.; Rodgers, M. T.

    2017-09-01

    The gas-phase conformations of transition metal cation-uracil complexes, [Ura+Cu]+ and [Ura+Ag]+, were examined via infrared multiple photon dissociation (IRMPD) action spectroscopy and theoretical calculations. IRMPD action spectra were measured over the IR fingerprint and hydrogen-stretching regions. Structures and linear IR spectra of the stable tautomeric conformations of these complexes were initially determined at the B3LYP/6-31G(d) level. The four most stable structures computed were also examined at the B3LYP/def2-TZVPPD level to improve the accuracy of the predicted IR spectra. Two very favorable modes of binding are found for [Ura+Cu]+ and [Ura+Ag]+ that involve O2N3 bidentate binding to the 2-keto-4-hydroxy minor tautomer and O4 monodentate binding to the canonical 2,4-diketo tautomer of Ura. Comparisons between the measured IRMPD and calculated IR spectra enable elucidation of the conformers present in the experiments. These comparisons indicate that both favorable binding modes are represented in the experimental tautomeric conformations of [Ura+Cu]+ and [Ura+Ag]+. B3LYP suggests that Cu+ exhibits a slight preference for O4 binding, whereas Ag+ exhibits a slight preference for O2N3 binding. In contrast, MP2 suggests that both Cu+ and Ag+ exhibit a more significant preference for O2N3 binding. The relative band intensities suggest that O4 binding conformers comprise a larger portion of the population for [Ura+Ag]+ than [Ura+Cu]+. The dissociation behavior and relative stabilities of the [Ura+M]+ complexes, M+ = Cu+, Ag+, H+, and Na+) are examined via energy-resolved collision-induced dissociation experiments. The IRMPD spectra, dissociation behaviors, and binding preferences of Cu+ and Ag+ are compared with previous and present results for those of H+ and Na+. [Figure not available: see fulltext.

  3. Timing and deciphering mitochondrial DNA macro-haplogroup R0 variability in Central Europe and Middle East

    Directory of Open Access Journals (Sweden)

    Göbel Tanja

    2008-07-01

    Full Text Available Abstract Background Nearly half of the West Eurasian assemblage of human mitochondrial DNA (mtDNA is fractioned into numerous sub-lineages of the predominant haplogroup (hg R0. Several hypotheses have been proposed on the origin and the expansion times of some R0 sub-lineages, which were partially inconsistent with each other. Here we describe the phylogenetic structure and genetic variety of hg R0 in five European populations and one population from the Middle East. Results Our analysis of 1,350 mtDNA haplotypes belonging to R0, including entire control region sequences and 45 single nucleotide polymorphisms from the coding region, revealed significant differences in the distribution of different sub-hgs even between geographically closely located regions. Estimates of coalescence times that were derived using diverse algorithmic approaches consistently affirmed that the major expansions of the different R0 hgs occurred in the terminal Pleistocene and early Holocene. Conclusion Given an estimated coalescence time of the distinct lineages of 10 – 18 kya, the differences in the distributions could hint to either limited maternal gene flow after the Last Glacial Maximum due to the alpine nature of the regions involved or to a stochastic loss of diversity due to environmental events and/or disease episodes occurred at different times and in distinctive regions. Our comparison of two different ways of obtaining the timing of the most recent common ancestor confirms that the time of a sudden expansion can be adequately recovered from control region data with valid confidence intervals. For reliable estimates, both procedures should be applied in order to cross-check the results for validity and soundness.

  4. Conformational stability, spectral analysis (infrared, Raman and NMR) and DFT calculations of 2-Amino-5-(ethylthio)-1,3,4-thiadiazole

    Science.gov (United States)

    Mohamed, Tarek A.; Hassan, Ahmed E.; Shaaban, Ibrahim A.; Abuelela, Ahmed M.; Zoghaib, Wajdi M.

    2017-02-01

    The infrared (4000-225 cm-1) and Raman (3500-60 cm-1) spectra of 2-Amino-5-(ethylthio)-1,3,4-thiadiazole (AEST; C4H7N3S2) have been recorded in the solid phase. In addition, the 1H and 13C NMR spectra of AEST were obtained in DMSO-d6. We have focused on five staggered conformers (1-5) resulting from rotations of the methyl, ethyl and thioethyl groups around Csbnd C and Csbnd S bonds with the sbnd NH2 group having a non-planar (sp3) geometry. DFT-B3LYP/6-31G(d) calculations proved that only conformers 4 and 5 produce real vibrational frequencies and conformer 5 is the favored one with an energy difference of 124 cm-1 (0.35 kcal/mol) in agreement with the observed ethyl torsion at 92 cm-1. The calculated frequencies, infrared intensities, Raman activities and potential energy distributions were compiled with spectral observations in favor of conformer 5. All vibrational modes were assigned to their corresponding vibrational bands. Applying the observed methyl torsions, the kinetic parameter F number was found to be 5.3263 cm-1 and an average V3 value of 1565 ± 14 cm-1 (4.48 ± 0.04 kcal/mol) was obtained. These values are close to the methyl barriers predicted from B3LYP/6-31G(d) potential surface scans. Moreover, the 1H and 13C NMR chemical shifts were also estimated for conformers 4 and 5 with DMSO as solvent implementing GIAO/PCM approximation utilizing B3LYP method at 6-311++G (d,p) basis set. The results are reported and discussed herein and compared with 2-Amino-5-ethyl-1,3,4-thiadiazole (AET) whenever appropriate.

  5. Thermal-induced conformational changes in the product release area drive the enzymatic activity of xylanases 10B: Crystal structure, conformational stability and functional characterization of the xylanase 10B from Thermotoga petrophila RKU-1

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Camila Ramos; Meza, Andreia Navarro [Laboratorio Nacional de Biociencias (LNBio), Centro Nacional de Pesquisa em Energia e Materiais, Campinas, SP (Brazil); Hoffmam, Zaira Bruna; Silva, Junio Cota; Alvarez, Thabata Maria; Ruller, Roberto [Laboratorio Nacional de Ciencia e Tecnologia do Bioetanol (CTBE), Centro Nacional de Pesquisa em Energia e Materiais, Campinas, SP (Brazil); Giesel, Guilherme Menegon; Verli, Hugo [Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Squina, Fabio Marcio [Laboratorio Nacional de Ciencia e Tecnologia do Bioetanol (CTBE), Centro Nacional de Pesquisa em Energia e Materiais, Campinas, SP (Brazil); Prade, Rolf Alexander [Department of Microbiology and Molecular Genetics, Oklahoma State University, Stillwater, OK (United States); Murakami, Mario Tyago, E-mail: mario.murakami@lnbio.org.br [Laboratorio Nacional de Biociencias (LNBio), Centro Nacional de Pesquisa em Energia e Materiais, Campinas, SP (Brazil)

    2010-12-10

    Research highlights: {yields} The hyperthermostable xylanase 10B from Thermotoga petrophila RKU-1 produces exclusively xylobiose at the optimum temperature. {yields} Circular dichroism spectroscopy suggests a coupling effect of temperature-induced structural changes with its enzymatic behavior. {yields} Crystallographic and molecular dynamics studies indicate that conformational changes in the product release area modulate the enzyme action mode. -- Abstract: Endo-xylanases play a key role in the depolymerization of xylan and recently, they have attracted much attention owing to their potential applications on biofuels and paper industries. In this work, we have investigated the molecular basis for the action mode of xylanases 10B at high temperatures using biochemical, biophysical and crystallographic methods. The crystal structure of xylanase 10B from hyperthermophilic bacterium Thermotoga petrophila RKU-1 (TpXyl10B) has been solved in the native state and in complex with xylobiose. The complex crystal structure showed a classical binding mode shared among other xylanases, which encompasses the -1 and -2 subsites. Interestingly, TpXyl10B displayed a temperature-dependent action mode producing xylobiose and xylotriose at 20 {sup o}C, and exclusively xylobiose at 90 {sup o}C as assessed by capillary zone electrophoresis. Moreover, circular dichroism spectroscopy suggested a coupling effect of temperature-induced structural changes with this particular enzymatic behavior. Molecular dynamics simulations supported the CD analysis suggesting that an open conformational state adopted by the catalytic loop (Trp297-Lys326) provokes significant modifications in the product release area (+1,+2 and +3 subsites), which drives the enzymatic activity to the specific release of xylobiose at high temperatures.

  6. Ground- and excited-state stability of the conformers of 3,5-dinitrocatechol and its complexes with W(VI) and V(V): combined theoretical and experimental study.

    Science.gov (United States)

    Delchev, V B; Gavazov, K B; Shterev, I G

    2014-12-01

    We performed a theoretical and experimental study of the (photo)stability of 3,5-dinitrocatechol (DNC) and its complexes with W(VI) and V(V). The investigation showed that irradiation of DNC is accompanied by a parallel proton migration from the hydroxy group to the neighboring NO2 group, which results in a large Stokes shift of the absorption and emission bands. It was found that W(VI) forms a more stable 1:2 complex than V(V). The complex is stable even under UV irradiation. The most stable W(VI)(DNC)2 conformer is comprised of two mutually perpendicular DNC molecules as ligands.

  7. Conformational Transitions

    Science.gov (United States)

    Czerminski, Ryszard; Roitberg, Adrian; Choi, Chyung; Ulitsky, Alexander; Elber, Ron

    1991-10-01

    Two computational approaches to study plausible conformations of biological molecules and the transitions between them are presented and discussed. The first approach is a new search algorithm which enhances the sampling of alternative conformers using a mean field approximation. It is argued and demonstrated that the mean field approximation has a small effect on the location of the minima. The method is a combination of the LES protocol (Locally Enhanced Sampling) and simulated annealing. The LES method was used in the past to study the diffusion pathways of ligands from buried active sites in myoglobin and leghemoglobin to the exterior of the protein. The present formulation of LES and its implementation in a Molecular Dynamics program is described. An application for side chain placement in a tetrapeptide is presented. The computational effort associated with conformational searches using LES grows only linearly with the number of degrees of freedom, whereas in the exact case the computational effort grows exponentially. Such saving is of course associated with a mean field approximation. The second branch of studies pertains to the calculation of reaction paths in large and flexible biological systems. An extensive mapping of minima and barriers for two different tetrapeptides is calculated from the known minima and barriers of alanine tetrapeptide which we calculated recently.1 The tetrapeptides are useful models for the formation of secondary structure elements since they are the shortest possible polymers of this type which can still form a complete helical turn. The tetrapeptides are isobutyryl-val(χ1=60)-ala-ala and isobutyryl-val(χ1=-60)-ala-ala. Properties of the hundreds of minima and of the hundreds intervening barriers are discussed. Estimates for thermal transition times between the many conformers (and times to explore the complete phase space) are calculated and compared. It is suggested that the most significant effect of the side chain size is

  8. From rigid cyclic templates to conformationally stabilized acyclic scaffolds. Part I: the discovery of CCR3 antagonist development candidate BMS-639623 with picomolar inhibition potency against eosinophil chemotaxis.

    Science.gov (United States)

    Santella, Joseph B; Gardner, Daniel S; Yao, Wenqing; Shi, Chongsheng; Reddy, Prabhakar; Tebben, Andrew J; DeLucca, George V; Wacker, Dean A; Watson, Paul S; Welch, Patricia K; Wadman, Eric A; Davies, Paul; Solomon, Kimberly A; Graden, Dani M; Yeleswaram, Swamy; Mandlekar, Sandhya; Kariv, Ilona; Decicco, Carl P; Ko, Soo S; Carter, Percy H; Duncia, John V

    2008-01-15

    Conformational analysis of trans-1,2-disubstituted cyclohexane CCR3 antagonist 2 revealed that the cyclohexane linker could be replaced by an acyclic syn-alpha-methyl-beta-hydroxypropyl linker. Synthesis and biological evaluation of mono- and disubstituted propyl linkers support this conformational correlation. It was also found that the alpha-methyl group to the urea lowered protein binding and that the beta-hydroxyl group lowered affinity for CYP2D6. Ab initio calculations show that the alpha-methyl group governs the spatial orientation of three key functionalities within the molecule. alpha-Methyl-beta-hydroxypropyl urea 31 with a chemotaxis IC(50)=38 pM for eosinophils was chosen to enter clinical development for the treatment of asthma.

  9. Estimating the Basic Reproductive Number (R0 for African Swine Fever Virus (ASFV Transmission between Pig Herds in Uganda.

    Directory of Open Access Journals (Sweden)

    Mike B Barongo

    Full Text Available African swine fever (ASF is a highly contagious, lethal and economically devastating haemorrhagic disease of domestic pigs. Insights into the dynamics and scale of virus transmission can be obtained from estimates of the basic reproduction number (R0. We estimate R0 for ASF virus in small holder, free-range pig production system in Gulu, Uganda. The estimation was based on data collected from outbreaks that affected 43 villages (out of the 289 villages with an overall pig population of 26,570 between April 2010 and November 2011. A total of 211 outbreaks met the criteria for inclusion in the study. Three methods were used, specifically; (i GIS- based identification of the nearest infectious neighbour based on the Euclidean distance between outbreaks, (ii epidemic doubling time, and (iii a compartmental susceptible-infectious (SI model. For implementation of the SI model, three approaches were used namely; curve fitting (CF, a linear regression model (LRM and the SI/N proportion. The R0 estimates from the nearest infectious neighbour and epidemic doubling time methods were 3.24 and 1.63 respectively. Estimates from the SI-based method were 1.58 for the CF approach, 1.90 for the LRM, and 1.77 for the SI/N proportion. Since all these values were above one, they predict the observed persistence of the virus in the population. We hypothesize that the observed variation in the estimates is a consequence of the data used. Higher resolution and temporally better defined data would likely reduce this variation. This is the first estimate of R0 for ASFV in a free range smallholder pig keeping system in sub-Saharan Africa and highlights the requirement for more efficient application of available disease control measures.

  10. Estimating the Basic Reproductive Number (R0) for African Swine Fever Virus (ASFV) Transmission between Pig Herds in Uganda.

    Science.gov (United States)

    Barongo, Mike B; Ståhl, Karl; Bett, Bernard; Bishop, Richard P; Fèvre, Eric M; Aliro, Tony; Okoth, Edward; Masembe, Charles; Knobel, Darryn; Ssematimba, Amos

    2015-01-01

    African swine fever (ASF) is a highly contagious, lethal and economically devastating haemorrhagic disease of domestic pigs. Insights into the dynamics and scale of virus transmission can be obtained from estimates of the basic reproduction number (R0). We estimate R0 for ASF virus in small holder, free-range pig production system in Gulu, Uganda. The estimation was based on data collected from outbreaks that affected 43 villages (out of the 289 villages with an overall pig population of 26,570) between April 2010 and November 2011. A total of 211 outbreaks met the criteria for inclusion in the study. Three methods were used, specifically; (i) GIS- based identification of the nearest infectious neighbour based on the Euclidean distance between outbreaks, (ii) epidemic doubling time, and (iii) a compartmental susceptible-infectious (SI) model. For implementation of the SI model, three approaches were used namely; curve fitting (CF), a linear regression model (LRM) and the SI/N proportion. The R0 estimates from the nearest infectious neighbour and epidemic doubling time methods were 3.24 and 1.63 respectively. Estimates from the SI-based method were 1.58 for the CF approach, 1.90 for the LRM, and 1.77 for the SI/N proportion. Since all these values were above one, they predict the observed persistence of the virus in the population. We hypothesize that the observed variation in the estimates is a consequence of the data used. Higher resolution and temporally better defined data would likely reduce this variation. This is the first estimate of R0 for ASFV in a free range smallholder pig keeping system in sub-Saharan Africa and highlights the requirement for more efficient application of available disease control measures.

  11. New population and phylogenetic features of the internal variation within mitochondrial DNA macro-haplogroup R0.

    Directory of Open Access Journals (Sweden)

    Vanesa Alvarez-Iglesias

    Full Text Available BACKGROUND: R0 embraces the most common mitochondrial DNA (mtDNA lineage in West Eurasia, namely, haplogroup H (approximately 40%. R0 sub-lineages are badly defined in the control region and therefore, the analysis of diagnostic coding region polymorphisms is needed in order to gain resolution in population and medical studies. METHODOLOGY/PRINCIPAL FINDINGS: We sequenced the first hypervariable segment (HVS-I of 518 individuals from different North Iberian regions. The mtDNAs belonging to R0 (approximately 57% were further genotyped for a set of 71 coding region SNPs characterizing major and minor branches of R0. We found that the North Iberian Peninsula shows moderate levels of population stratification; for instance, haplogroup V reaches the highest frequency in Cantabria (north-central Iberia, but lower in Galicia (northwest Iberia and Catalonia (northeast Iberia. When compared to other European and Middle East populations, haplogroups H1, H3 and H5a show frequency peaks in the Franco-Cantabrian region, declining from West towards the East and South Europe. In addition, we have characterized, by way of complete genome sequencing, a new autochthonous clade of haplogroup H in the Basque country, named H2a5. Its coalescence age, 15.6+/-8 thousand years ago (kya, dates to the period immediately after the Last Glacial Maximum (LGM. CONCLUSIONS/SIGNIFICANCE: In contrast to other H lineages that experienced re-expansion outside the Franco-Cantabrian refuge after the LGM (e.g. H1 and H3, H2a5 most likely remained confined to this area till present days.

  12. Internal diversification of mitochondrial haplogroup R0a reveals post-last glacial maximum demographic expansions in South Arabia.

    Science.gov (United States)

    Cerný, Viktor; Mulligan, Connie J; Fernandes, Verónica; Silva, Nuno M; Alshamali, Farida; Non, Amy; Harich, Nourdin; Cherni, Lotfi; El Gaaied, Amel Ben Ammar; Al-Meeri, Ali; Pereira, Luísa

    2011-01-01

    Widespread interest in the first successful Out of Africa dispersal of modern humans ∼60-80 thousand years ago via a southern migration route has overshadowed the study of later periods of South Arabian prehistory. In this work, we show that the post-Last Glacial Maximum period of the past 20,000 years, during which climatic conditions were becoming more hospitable, has been a significant time in the formation of the extant genetic composition and population structure of this region. This conclusion is supported by the internal diversification displayed in the highly resolved phylogenetic tree of 89 whole mitochondrial genomes (71 being newly presented here) for haplogroup R0a-the most frequent and widespread haplogroup in Arabia. Additionally, two geographically specific clades (R0a1a1a and R0a2f1) have been identified in non-Arabic speaking peoples such as the Soqotri and Mahri living in the southern part of the Arabian Peninsula where a past refugium was identified by independent archaeological studies. Estimates of time to the most recent common ancestor of these lineages match the earliest archaeological evidence for seafaring activity in the peninsula in the sixth millennium BC.

  13. Stability

    Directory of Open Access Journals (Sweden)

    Nada S. Abdelwahab

    2017-05-01

    Full Text Available The present work concerns with the development of stability indicating the RP-HPLC method for simultaneous determination of guaifenesin (GUF and pseudoephedrine hydrochloride (PSH in the presence of guaifenesin related substance (Guaiacol. GUC, and in the presence of syrup excepients with minimum sample pre-treatment. In the developed RP-HPLC method efficient chromatographic separation was achieved for GUF, PSH, GUC and syrup excepients using ODS column as a stationary phase and methanol: water (50:50, v/v, pH = 4 with orthophosphoric acid as a mobile phase with a flow rate of 1 mL min−1 and UV detection at 210 nm. The chromatographic run time was approximately 10 min. Calibration curves were drawn relating the integrated area under peak to the corresponding concentrations of PSH, GUF and GUC in the range of 1–8, 1–20, 0.4–8 μg mL−1, respectively. The developed method has been validated and met the requirements delineated by ICH guidelines with respect to linearity, accuracy, precision, specificity and robustness. The validated method was successfully applied for determination of the studied drugs in triaminic chest congestion® syrup; moreover its results were statistically compared with those obtained by the official method and no significant difference was found between them.

  14. Infrared, Raman and NMR spectra, conformational stability, normal coordinate analysis and B3LYP calculations of 5-amino-4-cyano-3-(methylthio)-1H-pyrazole-1-carbothioamide

    Science.gov (United States)

    Mohamed, Tarek A.; Hassan, Ali M.; Soliman, Usama A.; Zoghaib, Wajdi M.; Husband, John; Abdelall, Mahmoud M.

    2011-01-01

    The Raman and infrared spectra of solid 5-amino-4-cyano-3-(methylthio)-1H-pyrazole-1-carbothioamide (AMPC, C 6H 7N 5S 2) were measured in the spectral range of 3700-100 cm -1 and 4000-200 cm -1 with a resolution of 4 and 0.5 cm -1, respectively. Aided by normal coordinate analysis and potential energy distributions, a confident vibrational assignment of all fundamentals is proposed herein. As a result of internal rotation around C sbnd N and/or C sbnd S bonds, 32 rotational isomers are suggested for AMPC (C s symmetry). RHF and DFT/B3LYP quantum mechanical calculations including polarization and diffusion functions up to 6-311++G(d,p) basis sets, predict that after complete relaxation of the 32 possible isomers, four structures lie within 1500 cm -1 of the lowest energy conformer. However, vibrational analysis reveals the lowest energy conformer to be the only structure giving all real frequencies. Thus, the only stable conformer of AMPC is shown to have a fully planar skeleton with the NH 2 groups trans to one another. The recorded IR and Raman spectral measurements favor the calculated structural parameters which are further supported by spectral simulation. Additional support is given by 1H and 13C NMR spectra recorded with the sample dissolved in DMSO-d 6 and by predicted chemical shifts at the B3LYP/6-311+G(2d,p) level obtained using the Gauge-Invariant Atomic Orbitals (GIAO) method with and without inclusion of solvent using the Polarizable Continuum Model (PCM). Finally, CH 3, CH 3S, and NH 2 torsional barriers to internal rotation have been investigated using the optimized structural parameters from the B3LYP method with the 6-31G(d) basis set. The results are discussed herein and compared with similar molecules whenever appropriate.

  15. Conformational stability, molecular structure, vibrational, electronic, 1H and 13C spectral analysis of 3-pyridinemethanol using ab-initio/DFT method

    Science.gov (United States)

    Sivaranjani, T.; Periandy, S.; Xavier, S.

    2016-03-01

    The FT-IR and FT-Raman spectra of 3-pyridinemethanol (3PYRM) have been recorded in the regions 4000-400 and 4000-100 cm-1 respectively. The vibrational analysis of 3PYRM was carried out using wavenumbers computed by HF and DFT (B3LYP) methods with 6-311++G (d, p) basis set, along with experimental values. The conformational analyses were performed and the energies of the different possible conformers were determined. The total electron density and MESP surfaces of the molecules were constructed using B3LYP/6-311++G (d, p) method to display nucleophilic and electrophilic region globally. The HOMO and LUMO energies were measured and different reactivity descriptors are discussed the active sites of the molecule. Natural Bond Orbital Analysis is discussed and possible transition are correlated with the electronic transitions. Milliken's net charges and the atomic natural charges are also predicted. The 13C and 1H NMR chemical shifts were computed at the B3LYP/6-311++G (2d, p) level by applying GIAO theory and compared with the experimental spectra recorded using the high resolution of 100 MHz and 400 MHz NMR spectrometer with electromagnetic field strength 9.1T, respectively. The temperature dependence of the thermodynamic properties; heat capacity, entropy and enthalpy for the title compounds were also determined by B3LYP/6-311++G (d, p) method.

  16. Prognostic Significance of Peritoneal Metastasis in Stage IV Colorectal Cancer Patients With R0 Resection: A Multicenter, Retrospective Study.

    Science.gov (United States)

    Arakawa, Keiichi; Kawai, Kazushige; Ishihara, Soichiro; Hata, Keisuke; Nozawa, Hiroaki; Oba, Koji; Sugihara, Kenichi; Watanabe, Toshiaki

    2017-10-01

    Stage IV colorectal cancer encompasses various clinical conditions. The differences in prognosis after surgery between different metastatic organs have not been fully investigated. This study aimed to assess prognostic significance in peritoneal metastasis in R0 resected stage IV colorectal cancer. We conducted a multicenter retrospective study of patients with R0 resected stage IV colorectal cancer; they were categorized into 3 groups according to the number and location of metastatic organs, including single-organ metastasis in the peritoneum, single-organ metastasis at sites except the peritoneum, and multiple-organ metastases. This study used data accumulated by the Japanese Study Group for Postoperative Follow-Up of Colorectal Cancer. A total of 1133 patients with R0 resected stage IV colorectal cancer were registered retrospectively between 1997 and 2007 in 20 referral hospitals. Cancer-specific survival rates between the groups were measured. The median cancer-specific survival of the single-organ metastasis in the peritoneum group was considerably shorter than that of the single-organ metastasis at a site other than the peritoneum group and was almost comparable to that of the multiple-organ metastases group (3.41 years, 6.20 years, and 2.99 years). In a multivariate analysis of cancer-specific survival, peritoneal dissemination was confirmed as an independent prognostic factor of survival. The median postrecurrence survival of single-organ metastasis in the peritoneum group was considerably shorter than that of the single-organ metastasis at a site other than the peritoneum group. Approximately half of the patients who experienced recurrence of single-organ metastasis in the peritoneum experienced peritoneal recurrence. This was a retrospective, population-based study that requires a prospective design to validate its conclusions. Peritoneal metastasis of colorectal cancer frequently recurred in the peritoneum even after R0 resection. The cancer

  17. Dynamic conformations of nucleophosmin (NPM1 at a key monomer-monomer interface affect oligomer stability and interactions with granzyme B.

    Directory of Open Access Journals (Sweden)

    Wei D Duan-Porter

    Full Text Available Nucleophosmin (NPM1 is an abundant, nucleolar tumor antigen with important roles in cell proliferation and putative contributions to oncogenesis. Wild-type NPM1 forms pentameric oligomers through interactions at the amino-terminal core domain. A truncated form of NPM1 found in some hepatocellular carcinoma tissue formed an unusually stable oligomer and showed increased susceptibility to cleavage by granzyme B. Initiation of translation at the seventh methionine generated a protein (M7-NPM that shared all these properties. We used deuterium exchange mass spectrometry (DXMS to perform a detailed structural analysis of wild-type NPM1 and M7-NPM, and found dynamic conformational shifts or local "unfolding" at a specific monomer-monomer interface which included the β-hairpin "latch." We tested the importance of interactions at the β-hairpin "latch" by replacing a conserved tyrosine in the middle of the β-hairpin loop with glutamic acid, generating Y67E-NPM. Y67E-NPM did not form stable oligomers and further, prevented wild-type NPM1 oligomerization in a dominant-negative fashion, supporting the critical role of the β-hairpin "latch" in monomer-monomer interactions. Also, we show preferential cleavage by granzyme B at one of two available aspartates (either D161 or D122 in M7-NPM and Y67E-NPM, whereas wild-type NPM1 was cleaved at both sites. Thus, we observed a correlation between the propensity to form oligomers and granzyme B cleavage site selection in nucleophosmin proteins, suggesting that a small change at an important monomer-monomer interface can affect conformational shifts and impact protein-protein interactions.

  18. Conformal Gravity rotation curves with a conformal Higgs halo

    Science.gov (United States)

    Horne, Keith

    2016-06-01

    We discuss the effect of a conformally coupled Higgs field on conformal gravity (CG) predictions for the rotation curves of galaxies. The Mannheim-Kazanas (MK) metric is a valid vacuum solution of CG's fourth-order Poisson equation if and only if the Higgs field has a particular radial profile, S(r) = S0 a/(r + a), decreasing from S0 at r = 0 with radial scalelength a. Since particle rest masses scale with S(r)/S0, their world lines do not follow time-like geodesics of the MK metric gμν, as previously assumed, but rather those of the Higgs-frame MK metric tilde{g}_{μ ν }=Ω ^2 g_{μ ν }, with the conformal factor Ω(r) = S(r)/S0. We show that the required stretching of the MK metric exactly cancels the linear potential that has been invoked to fit galaxy rotation curves without dark matter. We also formulate, for spherical structures with a Higgs halo S(r), the CG equations that must be solved for viable astrophysical tests of CG using galaxy and cluster dynamics and lensing.

  19. Comparison of Different Risk Classification Systems in 558 Patients with Gastrointestinal Stromal Tumors after R0-Resection

    Science.gov (United States)

    Schmieder, Michael; Henne-Bruns, Doris; Mayer, Benjamin; Knippschild, Uwe; Rolke, Claudia; Schwab, Matthias; Kramer, Klaus

    2016-01-01

    Background: Due to adjuvant treatment concepts for patients with R0-resected gastrointestinal stromal tumors (GIST), a reproducible and reliable risk classification system proved of utmost importance for optimal treatment of patients and prediction of prognosis. The aim of this study was to reevaluate the impact of five widely-applied and well-established GIST risk classification systems (i.e., scores by Fletcher, Miettinen, Huang, Joensuu, and TNM classification) on a series of 558 GIST patients with long-term follow-up after R0 resection. Methods: Tumor size, mitotic count and site were used in variable combination to predict high- and low risk patients by the use of the five risk classification models. For survival analyses disease-specific survival, disease-free survival and overall-survival were investigated. Patients with initial metastatic disease or incompletely resectable tumors were excluded. Results: All GIST classification models distinguished well between patients with high-risk and low-risk tumors and none of the five risk systems was superior to predict patient outcome. The models showed significant heterogeneity. There was no significant difference between the different risk-groups regarding overall-survival. Subdivision of GIST patients with very low- and low-risk appeared to be negligible. Conclusions: Currently applied GIST risk classification systems are comparable to predict high- or low-risk patients with initial non-metastatic and completely resected GIST. However, the heterogeneity of the high-risk group and the absence of differences in overall survival indicate the need for more precise tumor- and patient-related criteria for better stratification of GIST and identification of patients who would benefit best from adjuvant tyrosine kinase inhibitor therapy. PMID:28082898

  20. Conformational stability, spectroscopic and computational studies, HOMO-LUMO, NBO, ESP analysis, thermodynamic parameters of natural bioactive compound with anticancer potential of 2-(hydroxymethyl)anthraquinone.

    Science.gov (United States)

    Balachandran, V; Karpagam, V; Revathi, B; Kavimani, M; Ilango, G

    2015-11-05

    Natural product drugs play a dominant role in pharmaceutical care. Nature is an attractive source of new therapeutic candidate compounds as a tremendous chemical diversity is found in millions of species of plants, animals, marine organism and micro-organism. A antifungal activity against important opportunist micro-organism and against those involved in superficial mycosis, all from nosocomial origin. The acute in vitro cytotoxicity evaluation of each anthraquinone (AQ) isolated from these bioactive extracts, on a mammalian eukaryotic cell line (Vero cells), allowed us to establish the non-cytotoxic concentration range, which was used to evaluate the anti-microbial effect. A comprehensive ab initio calculation using the DFT/6-31+G(d) level theory showed that 2-(hydroxymethyl)anthraquinone can exist in four possible conformations, which can interchange through the OH group on the five-membered ring. Density functional theory calculations were used to predict the vibrational frequencies and to help in normal mode, assignments. Furthermore, a natural bond orbital analysis was performed describing each hydrogen bond as donor accepter interaction. The Fourier transform infrared spectra (4000-400 cm(-1)) and the Fourier transform Raman spectra (3500-100 cm(-1)) of the HMA in the solid space have been recorded. The calculated HOMO and LUMO energies show that charge transfer occurs within the molecule. The calculated ESP contour map shows the electrophilic and nucleophilic region of the molecule.

  1. Conformal transformations and conformal invariance in gravitation

    CERN Document Server

    Dabrowski, Mariusz P; Blaschke, David B

    2008-01-01

    Conformal transformations are frequently used tools in order to study relations between various theories of gravity and Einstein relativity. Because of that, in this paper we discuss the rules of conformal transformations for geometric quantities in general relativity. In particular, we discuss the conformal transformations of the matter energy-momentum tensor. We thoroughly discuss the latter and show the subtlety of the conservation law (i.e., the geometrical Bianchi identity) imposed in one of the conformal frames in reference to the other. The subtlety refers to the fact that conformal transformation ``creates'' an extra matter term composed of the conformal factor which enters the conservation law. In an extreme case of the flat original spacetime the matter is ``created'' due to work done by the conformal transformation to bend the spacetime which was originally flat. We also discuss how to construct the conformally invariant gravity which, in the simplest version, is a special case of the Brans-Dicke t...

  2. Influence of hyperthermophilic protein Cren7 on the stability and conformation of DNA: insights from molecular dynamics simulation and free energy analysis.

    Science.gov (United States)

    Chen, Lin; Zhang, Ji-Long; Yu, Li-Ying; Zheng, Qing-Chuan; Chu, Wen-Ting; Xue, Qiao; Zhang, Hong-Xing; Sun, Chia-Chung

    2012-10-18

    Cren7, a novel chromatin protein highly conserved among crenarchaea, plays an important role in genome packaging and gene regulation. However, the detail dynamical structural characteristic of the Cren7-DNA complex and the detail study of the DNA in the complex have not been done. Focused on two specific Cren7-DNA complexes (PDB codes 3LWH and 3LWI ), we applied molecular dynamics (MD) simulations at four different temperatures (300, 350, 400, and 450 K) and the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) free energy calculation at 300 and 350 K to examine the role of Cren7 protein in enhancing the stability of DNA duplexes via protein-DNA interactions, and to study the structural transition in DNA. The simulation results indicate that Cren7 stabilizes DNA duplex in a certain temperature range in the binary complex compared with the unbound DNA molecules. At the same time, DNA molecules were found to undergo B-like to A-like form transitions with increased temperature. The results of statistical analyses of the H-bond and hydrophobic contacts show that some residues have significant influence on the structure of DNA molecules. Our work can give important information to understand the interactions of proteins with nucleic acids and other ligands.

  3. Conformal isoparametric hypersurfaces with two distinct conformal principal curvatures in conformal space

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    The conformal geometry of regular hypersurfaces in the conformal space is studied.We classify all the conformal isoparametric hypersurfaces with two distinct conformal principal curvatures in the conformal space up to conformal equivalence.

  4. Conformational analysis of large and highly disulfide-stabilized proteins by integrating online electrochemical reduction into an optimized H/D exchange mass spectrometry workflow

    DEFF Research Database (Denmark)

    Trabjerg, Esben; Jakobsen, Rasmus Uffe; Mysling, Simon

    2015-01-01

    Analysis of disulfide-bonded proteins by HDX-MS requires effective and rapid reduction of disulfide bonds before enzymatic digestion in order to increase sequence coverage. In a conventional HDX-MS workflow, disulfide bonds are reduced chemically by addition of a reducing agent to the quench...... the electrochemical reduction efficiency during HDX-MS analysis of two particularly challenging disulfide stabilized proteins: a therapeutic IgG1-antibody and Nerve Growth Factor-β (NGF). Several different parameters (flow rate, applied square wave potential as well as the type of labeling- and quench buffer) were......-antibody, respectively. The presented results demonstrate the successful electrochemical reduction during HDX-MS analysis of both a small exceptional tightly disulfide-bonded protein (NGF) as well as the largest protein attempted to date (IgG1-antibody). We envision that online electrochemical reduction...

  5. Prognostic Factors and Patterns of Relapse in Ewing Sarcoma Patients Treated With Chemotherapy and R0 Resection

    Energy Technology Data Exchange (ETDEWEB)

    Pan, Hubert Y. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Morani, Ajaykumar [Department of Radiology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Wang, Wei-Lien [Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Hess, Kenneth R. [Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Paulino, Arnold C. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Ludwig, Joseph A. [Department of Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Lin, Patrick P. [Department of Orthopedic Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Daw, Najat C. [Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mahajan, Anita, E-mail: amahajan@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2015-06-01

    Purpose: To identify prognostic factors and patterns of relapse for patients with Ewing sarcoma who underwent chemotherapy and R0 resection without radiation therapy (RT). Methods and Materials: We reviewed the medical records of patients who underwent surgical resection at our institution between 2000 and 2013 for an initial diagnosis of Ewing sarcoma. The associations of demographic and clinical factors with local control (LC) and patient outcome were determined by Cox regression. Time to events was measured from the time of surgery. Survival curves were estimated by the Kaplan-Meier method and compared by the log-rank test. Results: A total of 66 patients (median age 19 years, range 4-55 years) met the study criteria. The median follow-up was 5.6 years for living patients. In 43 patients (65%) for whom imaging studies were available, the median tumor volume reduction was 73%, and at least partial response by Response Evaluation Criteria in Solid Tumors was achieved in 17 patients (40%). At 5 years, LC was 78%, progression-free survival (PFS) was 59%, and overall survival (OS) was 65%. Poor histologic response (necrosis ≤95%) was an independent predictor of LC (hazard ratio [HR] 6.8, P=.004), PFS (HR 5.2, P=.008), and OS (HR 5.0, P=.008). Metastasis on presentation was also an independent predictor of LC (HR 6.3, P=.011), PFS (HR 6.8, P=.002), and OS (HR 6.7, P=.002). Radiologic partial response was a predictor of PFS (HR 0.26, P=.012), and postchemotherapy tumor volume was associated with OS (HR 1.06, P=.015). All deaths were preceded by distant relapse. Of the 8 initial local-only relapses, 5 (63%) were soon followed by distant relapse. Predictors of poor postrecurrence survival were time to recurrence <1 year (HR 11.5, P=.002) and simultaneous local and distant relapse (HR 16.8, P=.001). Conclusions: Histologic and radiologic response to chemotherapy were independent predictors of outcome. Additional study is needed to determine the role of adjuvant

  6. Tumores del estroma gastrointestinal (GIST: factores pronósticos de supervivencia tras citorreducción R0 Gastrointestinal stromal tumors (GIST: factors predictive of survival after R0-cytoreduction

    Directory of Open Access Journals (Sweden)

    J. M. Sánchez Hidalgo

    2007-12-01

    Full Text Available Objetivo: analizar los posibles factores pronósticos de supervivencia en tumores estromales gastrointestinales c-kit positivo (GIST, tras citorreducción óptima R0. Pacientes y método: estudio de 35 pacientes intervenidos en nuestra Unidad desde enero 2002 a febrero 2007, con tumores del estroma gastrointestinal CD117/c-kit positivo en los que se alcanzó citorreducción quirúrgica sin residuo tumoral macroscópico. Una base de datos prospectiva nos proporcionó las distintas variables analizadas, de carácter demográfico, anatómico, clínico, histopatológico e inmunohistoquímico, entre otras. El análisis de la supervivencia actuarial se realizó según el método de Kaplan-Meier y el análisis multivariante mediante el método de regresión múltiple de Cox. Resultados: la supervivencia global a 5 años fue del 77%, con una supervivencia media de 52 meses. El riesgo de malignidad según la clasificación de Fletcher y el tamaño tumoral mayor de 10 cm, influyeron significativamente de forma negativa sobre la supervivencia de los pacientes, tras el análisis univariante realizado (p 50% y vivos en la actualidad. Conclusiones: el índice proliferativo Ki-67 podría representar un excelente marcador pronóstico de supervivencia en aquellos pacientes con tumores del estroma gastrointestinal c-kit positivo. Su confirmación y el punto de corte adecuado deberían ser objeto de futuros estudios prospectivos, así como su posible utilidad para seleccionar pacientes candidatos al tratamiento con mesilato de imatinib.Objective: to analyze the different factors predictive of survival associated with optimal R0-cytoreduction in c-kit-positive gastrointestinal stromal tumors. Methods: thirty-five patients were operated on in our Oncological Surgery Department from January 2002 to February 2007 because of CD117/c-kit-positive gastrointestinal stromal tumors, and an optimal surgical cytoreduction was obtained without macroscopical residual disease

  7. A high reliability survey of discrete Epoch of Reionization foreground sources in the MWA EoR0 field

    Science.gov (United States)

    Carroll, P. A.; Line, J.; Morales, M. F.; Barry, N.; Beardsley, A. P.; Hazelton, B. J.; Jacobs, D. C.; Pober, J. C.; Sullivan, I. S.; Webster, R. L.; Bernardi, G.; Bowman, J. D.; Briggs, F.; Cappallo, R. J.; Corey, B. E.; de Oliveira-Costa, A.; Dillon, J. S.; Emrich, D.; Ewall-Wice, A.; Feng, L.; Gaensler, B. M.; Goeke, R.; Greenhill, L. J.; Hewitt, J. N.; Hurley-Walker, N.; Johnston-Hollitt, M.; Kaplan, D. L.; Kasper, J. C.; Kim, HS.; Kratzenberg, E.; Lenc, E.; Loeb, A.; Lonsdale, C. J.; Lynch, M. J.; McKinley, B.; McWhirter, S. R.; Mitchell, D. A.; Morgan, E.; Neben, A. R.; Oberoi, D.; Offringa, A. R.; Ord, S. M.; Paul, S.; Pindor, B.; Prabu, T.; Procopio, P.; Riding, J.; Rogers, A. E. E.; Roshi, A.; Shankar, N. Udaya; Sethi, S. K.; Srivani, K. S.; Subrahmanyan, R.; Tegmark, M.; Thyagarajan, Nithyanandan; Tingay, S. J.; Trott, C. M.; Waterson, M.; Wayth, R. B.; Whitney, A. R.; Williams, A.; Williams, C. L.; Wu, C.; Wyithe, J. S. B.

    2016-10-01

    Detection of the epoch of reionization H I signal requires a precise understanding of the intervening galaxies and AGN, both for instrumental calibration and foreground removal. We present a catalogue of 7394 extragalactic sources at 182 MHz detected in the RA = 0 field of the Murchison Widefield Array Epoch of Reionization observation programme. Motivated by unprecedented requirements for precision and reliability we develop new methods for source finding and selection. We apply machine learning methods to self-consistently classify the relative reliability of 9490 source candidates. A subset of 7466 are selected based on reliability class and signal-to-noise ratio criteria. These are statistically cross-matched to four other radio surveys using both position and flux density information. We find 7369 sources to have confident matches, including 90 partially resolved sources that split into a total of 192 sub-components. An additional 25 unmatched sources are included as new radio detections. The catalogue sources have a median spectral index of -0.85. Spectral flattening is seen towards lower frequencies with a median of -0.71 predicted at 182 MHz. The astrometric error is 7 arcsec compared to a 2.3 arcmin beam FWHM. The resulting catalogue covers ˜1400 deg2 and is complete to approximately 80 mJy within half beam power. This provides the most reliable discrete source sky model available to date in the MWA EoR0 field for precision foreground subtraction.

  8. Conformational analysis of small molecules: NMR and quantum mechanics calculations.

    Science.gov (United States)

    Tormena, Cláudio F

    2016-08-01

    This review deals with conformational analysis in small organic molecules, and describes the stereoelectronic interactions responsible for conformational stability. Conformational analysis is usually performed using NMR spectroscopy through measurement of coupling constants at room or low temperature in different solvents to determine the populations of conformers in solution. Quantum mechanical calculations are used to address the interactions responsible for conformer stability. The conformational analysis of a large number of small molecules is described, using coupling constant measurements in different solvents and at low temperature, as well as recent applications of through-space and through-hydrogen bond coupling constants JFH as tools for the conformational analysis of fluorinated molecules. Besides NMR parameters, stereoelectronic interactions such as conjugative, hyperconjugative, steric and intramolecular hydrogen bond interactions involved in conformational preferences are discussed.

  9. WE-D-204-03: A Six-Year Longitudinal Evaluation of the DICOM GSDF Conformance Stability of LCD Monitors

    Energy Technology Data Exchange (ETDEWEB)

    McKenney, S; Bevins, N; Flynn, M [Henry Ford Health System, Detroit, MI (United States); Olariu, E [William Beaumont Hospital, Royal Oak, MI (United States)

    2015-06-15

    Purpose: The calibration of monitors in radiology is critical to ensure a standardized reading environment. If left unchecked, monitors initially calibrated to follow the DICOM Grayscale Standard Display Function (GSDF) can fall out of calibration. This work presents a quantitative evaluation of the stability of a cohort of monitors with similar deployment times and clinical utilization. Methods: Fifty-four liquid crystal display (LCD) monitors (NEC L200ME) were deployed for clinical use in 2009. At that time, a subset of eight of these monitors were used to generate a look-up table (LUT) using the open-source software pacsDisplay. The software was used to load the LUT to the graphics card of the computer in order to make the monitors compliant with the GSDF. The luminance response of the monitors was evaluated twice over six years, once in 2011 and again in 2015. Results: As expected, the maximum luminance of the monitors decreased over time, with an average reduction from 2009 of 35% in 2011, and 53% in 2015. The luminance ratio (maximum luminance divided by the minimum) also decreased, with the all of the decrease occurring in the first two years (average 20%). There was an overall increase in relative error compared with the DICOM GSDF from measurement to measurement, indicating that deviation from the GSDF increases with monitor luminance reduction. Along with changes in luminance, several other issues were identified during the testing, including non-uniformities, bad pixels, and missing calibration software. Conclusion: From the initial installation of these monitors, most of the degradation occurred during the first two years, highlighting the importance of routine clinical testing of displays. Following such quality assurance, displays could be either re-calibrated or replaced depending on different thresholds. In addition, other issues not related to luminance could be identified and corrected.

  10. Conformational analysis of large and highly disulfide-stabilized proteins by integrating online electrochemical reduction into an optimized H/D exchange mass spectrometry workflow.

    Science.gov (United States)

    Trabjerg, Esben; Jakobsen, Rasmus U; Mysling, Simon; Christensen, Søren; Jørgensen, Thomas J D; Rand, Kasper D

    2015-09-01

    Analysis of disulfide-bonded proteins by hydrogen/deuterium exchange mass spectrometry (HDX-MS) requires effective and rapid reduction of disulfide bonds before enzymatic digestion in order to increase sequence coverage. In a conventional HDX-MS workflow, disulfide bonds are reduced chemically by addition of a reducing agent to the quench solution (e.g., tris(2-carboxyethyl)phosphine (TCEP)). The chemical reduction, however, is severely limited under quenched conditions due to a narrow time window as well as low pH and temperature. Here, we demonstrate the real-world applicability of integrating electrochemical reduction into an online HDX-MS workflow. We have optimized the electrochemical reduction efficiency during HDX-MS analysis of two particularly challenging disulfide stabilized proteins: a therapeutic IgG1-antibody and nerve growth factor-β (NGF). Several different parameters (flow rate and applied square wave potential, as well as the type of labeling and quench buffer) were investigated, and the optimized workflow increased the sequence coverage of NGF from 46% with chemical reduction to 99%, when electrochemical reduction was applied. Additionally, the optimized workflow also enabled a similar high sequence coverage of 96% and 87% for the heavy and light chain of the IgG1-antibody, respectively. The presented results demonstrate the successful electrochemical reduction during HDX-MS analysis of both a small exceptional tightly disulfide-bonded protein (NGF) as well as the largest protein attempted to date (IgG1-antibody). We envision that online electrochemical reduction is poised to decrease the complexity of sample handling and increase the versatility of the HDX-MS technique.

  11. 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.

  12. Non-conformable, partial and conformable transposition

    DEFF Research Database (Denmark)

    König, Thomas; Mäder, Lars Kai

    2013-01-01

    Although member states are obliged to transpose directives into domestic law in a conformable manner and receive considerable time for their transposition activities, we identify three levels of transposition outcomes for EU directives: conformable, partially conformable and non-conformable....... Compared with existing transposition models, which do not distinguish between different transposition outcomes, we examine the factors influencing each transposition process by means of a competing risk analysis. We find that preference-related factors, in particular the disagreement of a member state...... 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...

  13. Potassium and ionic strength effects on the conformational and thermal stability of two aldehyde dehydrogenases reveal structural and functional roles of K⁺-binding sites.

    Directory of Open Access Journals (Sweden)

    Georgina Garza-Ramos

    Full Text Available Many aldehyde dehydrogenases (ALDHs have potential potassium-binding sites of as yet unknown structural or functional roles. To explore possible K(+-specific effects, we performed comparative structural studies on the tetrameric betaine aldehyde dehydrogenase from Pseudomonas aeruginosa (PaBADH and on the dimeric BADH from spinach (SoBADH, whose activities are K(+-dependent and K(+-independent, respectively, although both enzymes contain potassium-binding sites. Size exclusion chromatography, dynamic light scattering, far- and near-UV circular dichroism, and extrinsic fluorescence results indicated that in the absence of K(+ ions and at very low ionic strength, PaBADH remained tetrameric but its tertiary structure was significantly altered, accounting for its inactivation, whereas SoBADH formed tetramers that maintained the native tertiary structure. The recovery of PaBADH native tertiary-structure was hyperbolically dependent on KCl concentration, indicating potassium-specific structuring effects probably arising from binding to a central-cavity site present in PaBADH but not in SoBADH. K(+ ions stabilized the native structure of both enzymes against thermal denaturation more than did tetraethylammonium (TEA(+ ions. This indicated specific effects of potassium on both enzymes, particularly on PaBADH whose apparent T(m values showed hyperbolical dependence on potassium concentration, similar to that observed with the tertiary structure changes. Interestingly, we also found that thermal denaturation of both enzymes performed in low ionic-strength buffers led to formation of heat-resistant, inactive soluble aggregates that retain 80% secondary structure, have increased β-sheet content and bind thioflavin T. These structured aggregates underwent further thermal-induced aggregation and precipitation when the concentrations of KCl or TEACl were raised. Given that PaBADH and SoBADH belong to different ALDH families and differ not only in amino acid

  14. Evaluation of the effectiveness of selected measures against bovine spongiform encephalopathy (BSE) in Switzerland by use of the basic reproduction ratio R0.

    Science.gov (United States)

    Schwermer, Heinzpeter; Brülisauer, Franz; De Koeijer, Aline; Heim, Dagmar

    2007-01-01

    The effectiveness of two measures against Bovine Spongiform Encephalopathy (BSE), the compulsory processing of animal by products to meat and bone meal (MBM) at 133 degrees C under 3 bars of pressure for 20 minutes in February 1993 and the exclusion of fallen stock, heads with eyes and spinal cord of cattle older than 30 month from MBM production in April 1996, was evaluated in a process model. The transmission of BSE by calculation of the basic reproduction ratio R0 was modelled. The results were verified by use of a cohort model, based on observed surveillance data. Prior to 1990, before the ban of feeding MBM to ruminants, R0, as calculated in the process model, was above 1, coherent with a slowly progressing BSE epidemic. Since 1991, values of R0 were low at 0.06. The corresponding R0 values derived from the cohort model were higher, the lowest value 0.13 calculated for 1996. Given such low R0 values, the epidemic should have died out. Additionally, no influence of the two measures was obvious at that time given the low level of R0. The discrepancy between the results of the two models is evidence for a dependency of the BSE epidemic from an infection source not considered in the process model. This infection source is most likely importation of feed ingredients and MBM.

  15. Gauge Choice in Conformal Gravity

    Science.gov (United States)

    Sultana, Joseph; Kazanas, Demosthenes

    2017-01-01

    In a recent paper (MNRAS 458, 4122 (2016)) K. Horne examined the effect of a conformally coupled scalar field (referred to as Higgs field) on the Mannheim-Kazanas metric gμν, i.e. the static spherically symmetric metric within the context of conformal gravity (CG), and studied its effect on the rotation curves of galaxies. He showed that for a Higgs field of the form S(r) = S0a/(r + a), where a is a radial length scale, the equivalent Higgs-frame Mannheim-Kazanas metric tilde{g}_{μ ν } = Ω ^2 g_{μ ν }, with Ω = S(r)/S0, lacks the linear γr term, which has been employed in the fitting of the galactic rotation curves without the need to invoke dark matter. In this brief note we point out that the representation of the Mannheim-Kazanas metric in a gauge where it lacks the linear term has already been presented by others, including Mannheim and Kazanas themselves, without the need to introduce a conformally coupled Higgs field. Furthermore, Horne argues that the absence of the linear term resolves the issue of light bending in the wrong direction, i.e. away from the gravitating mass, if γr > 0 in the Mannheim-Kazanas metric, a condition necessary to resolve the galactic dynamics in the absence of dark matter. In this case we also point out that the elimination of the linear term is not even required because the sign of the γr term in the metric can be easily reversed by a simple gauge transformation, and also that the effects of this term are indeed too small to be observed.

  16. A geodesic model in conformal superspace

    CERN Document Server

    Gomes, Henrique de A

    2016-01-01

    In this paper, I look for the most general geometrodynamical symmetries compatible with spatial relational principles. I argue that they lead either to a completely static Universe, or one embodying spatial conformal diffeomorphisms. Demanding locality for an action compatible with these principles severely limits its form, both for the gravitational part as well as all matter couplings. The simplest and most natural choice for pure gravity has two propagating physical degrees of freedom (and no refoliation-invariance). The system has a geometric interpretation as a geodesic model in infinite dimensional conformal superspace. Conformal superspace is a stratified manifold, with different strata corresponding to different isometry groups. Choosing space to be (homeomorphic to) $S^3$, conformal superspace has a preferred stratum with maximal stabilizer group. This stratum consists of a single point -- corresponding to the conformal geometry of the round 3-sphere. This is the most homogeneous non-degenerate geome...

  17. 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....

  18. 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.

  19. A Plasmodium falciparum 48/45 single epitope R0.6C subunit protein elicits high levels of transmission blocking antibodies

    DEFF Research Database (Denmark)

    Singh, Susheel K; Roeffen, Will; Andersen, Gorm

    2015-01-01

    as a chimera with the N-terminal region of GLURP (R0). The resulting fusion protein elicited high titer TB antibodies in rodents. To increase the relatively low yield of correctly folded Pfs48/45 we have generated a series of novel chimera truncating the 10C-fragments to 6 cysteine residues containing sub...

  20. Crystallization and preliminary X-ray crystallographic analysis of the GluR0 ligand-binding core from Nostoc punctiforme

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jun Hyuck; Park, Soo Jeong; Rho, Seong-Hwan; Im, Young Jun; Kim, Mun-Kyoung; Kang, Gil Bu; Eom, Soo Hyun, E-mail: eom@gist.ac.kr [Department of Life Science, Gwangju Institute of Science and Technology, Gwangju 500-712 (Korea, Republic of)

    2005-11-01

    The GluR0 ligand-binding core from N. punctiforme was expressed, purified and crystallized in the presence of l-glutamate. A diffraction data set was collected to a resolution of 2.1 Å. GluR0 from Nostoc punctiforme (NpGluR0) is a bacterial homologue of the ionotropic glutamate receptor. The ligand-binding core of NpGluR0 was crystallized at 294 K using the hanging-drop vapour-diffusion method. The l-glutamate-complexed crystal belongs to space group C222{sub 1}, with unit-cell parameters a = 78.0, b = 145.1, c = 132.1 Å. The crystals contain three subunits in the asymmetric unit, with a V{sub M} value of 2.49 Å{sup 3} Da{sup −1}. The diffraction limit of the l-glutamate complex data set was 2.1 Å using synchrotron X-ray radiation at beamline BL-4A of the Pohang Accelerator Laboratory (Pohang, Korea)

  1. Performance of a Nomogram Predicting Disease-Specific Survival After an R0 Resection for Gastric Cancer in Patients Receiving Postoperative Chemoradiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Dikken, Johan L. [Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Department of Surgery, Leiden University Medical Center, Leiden (Netherlands); Coit, Daniel G. [Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Baser, Raymond E.; Gönen, Mithat [Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Goodman, Karyn A. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Brennan, Murray F. [Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Jansen, Edwin P.M. [Department of Radiotherapy, The Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Boot, Henk [Department of Gastroenterology, The Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Velde, Cornelis J.H. van de [Department of Surgery, Leiden University Medical Center, Leiden (Netherlands); Cats, Annemieke [Department of Gastroenterology, The Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Verheij, Marcel, E-mail: m.verheij@nki.nl [Department of Radiotherapy, The Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands)

    2014-03-01

    Purpose: The internationally validated Memorial Sloan-Kettering Cancer Center (MSKCC) gastric carcinoma nomogram was based on patients who underwent curative (R0) gastrectomy, without any other therapy. The purpose of the current study was to assess the performance of this gastric cancer nomogram in patients who received chemoradiation therapy after an R0 resection for gastric cancer. Methods and Materials: In a combined dataset of 76 patients from the Netherlands Cancer Institute (NKI), and 63 patients from MSKCC, who received postoperative chemoradiation therapy (CRT) after an R0 gastrectomy, the nomogram was validated by means of the concordance index (CI) and a calibration plot. Results: The concordance index for the nomogram was 0.64, which was lower than the CI of the nomogram for patients who received no adjuvant therapy (0.80). In the calibration plot, observed survival was approximately 20% higher than the nomogram-predicted survival for patients receiving postoperative CRT. Conclusions: The MSKCC gastric carcinoma nomogram significantly underpredicted survival for patients in the current study, suggesting an impact of postoperative CRT on survival in patients who underwent an R0 resection for gastric cancer, which has been demonstrated by randomized controlled trials. This analysis stresses the need for updating nomograms with the incorporation of multimodal strategies.

  2. Transitive conformal holonomy groups

    CERN Document Server

    Alt, Jesse

    2011-01-01

    For $(M,[g])$ a conformal manifold of signature $(p,q)$ and dimension at least three, the conformal holonomy group $\\mathrm{Hol}(M,[g]) \\subset O(p+1,q+1)$ is an invariant induced by the canonical Cartan geometry of $(M,[g])$. We give a description of all possible connected conformal holonomy groups which act transitively on the M\\"obius sphere $S^{p,q}$, the homogeneous model space for conformal structures of signature $(p,q)$. The main part of this description is a list of all such groups which also act irreducibly on $\\R^{p+1,q+1}$. For the rest, we show that they must be compact and act decomposably on $\\R^{p+1,q+1}$, in particular, by known facts about conformal holonomy the conformal class $[g]$ must contain a metric which is locally isometric to a so-called special Einstein product.

  3. Relating conformation to function in integrin α5β1.

    Science.gov (United States)

    Su, Yang; Xia, Wei; Li, Jing; Walz, Thomas; Humphries, Martin J; Vestweber, Dietmar; Cabañas, Carlos; Lu, Chafen; Springer, Timothy A

    2016-07-05

    Whether β1 integrin ectodomains visit conformational states similarly to β2 and β3 integrins has not been characterized. Furthermore, despite a wealth of activating and inhibitory antibodies to β1 integrins, the conformational states that these antibodies stabilize, and the relation of these conformations to function, remain incompletely characterized. Using negative-stain electron microscopy, we show that the integrin α5β1 ectodomain adopts extended-closed and extended-open conformations as well as a bent conformation. Antibodies SNAKA51, 8E3, N29, and 9EG7 bind to different domains in the α5 or β1 legs, activate, and stabilize extended ectodomain conformations. Antibodies 12G10 and HUTS-4 bind to the β1 βI domain and hybrid domains, respectively, activate, and stabilize the open headpiece conformation. Antibody TS2/16 binds a similar epitope as 12G10, activates, and appears to stabilize an open βI domain conformation without requiring extension or hybrid domain swing-out. mAb13 and SG/19 bind to the βI domain and βI-hybrid domain interface, respectively, inhibit, and stabilize the closed conformation of the headpiece. The effects of the antibodies on cell adhesion to fibronectin substrates suggest that the extended-open conformation of α5β1 is adhesive and that the extended-closed and bent-closed conformations are nonadhesive. The functional effects and binding sites of antibodies and fibronectin were consistent with their ability in binding to α5β1 on cell surfaces to cross-enhance or inhibit one another by competitive or noncompetitive (allosteric) mechanisms.

  4. Conformational regulation of urokinase receptor function

    DEFF Research Database (Denmark)

    Gårdsvoll, Henrik; Jacobsen, Benedikte; Kriegbaum, Mette C

    2011-01-01

    PA per se into the hydrophobic ligand binding cavity of uPAR that modulates the function of this receptor. Based on these data, we now propose a model in which the inherent interdomain mobility in uPAR plays a major role in modulating its function. Particularly one uPAR conformation, which is stabilized...

  5. Peptide N-Amination Supports β-Sheet Conformations.

    Science.gov (United States)

    Sarnowski, Matthew P; Kang, Chang Won; Elbatrawi, Yassin M; Wojtas, Lukasz; Del Valle, Juan R

    2017-02-13

    The conformational heterogeneity of backbone N-substituted peptides limits their ability to adopt stable secondary structures. Herein, we describe a practical synthesis of backbone aminated peptides that readily adopt β-sheet folds. Data derived from model N-amino peptides suggest that extended conformations are stabilized through cooperative steric, electrostatic, and hydrogen-bonding interactions.

  6. [Dosimetric evaluation of conformal radiotherapy: conformity factor].

    Science.gov (United States)

    Oozeer, R; Chauvet, B; Garcia, R; Berger, C; Felix-Faure, C; Reboul, F

    2000-01-01

    The aim of three-dimensional conformal therapy (3DCRT) is to treat the Planning Target Volume (PTV) to the prescribed dose while reducing doses to normal tissues and critical structures, in order to increase local control and reduce toxicity. The evaluation tools used for optimizing treatment techniques are three-dimensional visualization of dose distributions, dose-volume histograms, tumor control probabilities (TCP) and normal tissue complication probabilities (NTCP). These tools, however, do not fully quantify the conformity of dose distributions to the PTV. Specific tools were introduced to measure this conformity for a given dose level. We have extended those definitions to different dose levels, using a conformity index (CI). CI is based on the relative volumes of PTV and outside the PTV receiving more than a given dose. This parameter has been evaluated by a clinical study including 82 patients treated for lung cancer and 82 patients treated for prostate cancer. The CI was low for lung dosimetric studies (0.35 at the prescribed dose 66 Gy) due to build-up around the GTV and to spinal cord sparing. For prostate dosimetric studies, the CI was higher (0.57 at the prescribed dose 70 Gy). The CI has been used to compare treatment plans for lung 3DCRT (2 vs 3 beams) and prostate 3DCRT (4 vs 7 beams). The variation of CI with dose can be used to optimize dose prescription.

  7. On conformally related -waves

    Indian Academy of Sciences (India)

    Varsha Daftardar-Gejji

    2001-05-01

    Brinkmann [1] has shown that conformally related distinct Ricci flat solutions are -waves. Brinkmann's result has been generalized to include the conformally invariant source terms. It has been shown that [4] if $g_{ik}$ and $\\overline{g}_{ik}$ ($=^{-2}g_{ik}$, : a scalar function), are distinct metrics having the same Einstein tensor, $G_{ik}=\\overline{G}_{ik}$, then both represent (generalized) $pp$-waves and $_{i}$ is a null convariantly constant vector of $g_{ik}$. Thus $pp$-waves are the only candidates which yield conformally related nontrivial solutions of $G_{ik}=T_{ik}=\\overline{G}_{ik}$, with $T_{ik}$ being conformally invariant source. In this paper the functional form of the conformal factor for the conformally related $pp$-waves/generalized $pp$-waves has been obtained. It has been shown that the most general $pp$-wave, conformally related to ${\\rm d}s^{2}=-2{\\rm d}u[{\\rm d}v-m{\\rm d}y+H{\\rm d}u]+P^{-2}[{\\rm d}y^{2}+{\\rm d}z^{2}]$, turns out to the $(au+b)^{-2}{\\rm d}s^{2}$, where , are constants. Only in the special case when $m=0$, $H=1$, and $P=P(y,z)$, the conformal factor is $(au+b)^{-2}$ or $(a(u+v)+b)^{-2}$.

  8. Evidence for weak or linear conformity but not for hyper-conformity in an everyday social learning context

    National Research Council Canada - National Science Library

    Claidière, Nicolas; Bowler, Mark; Whiten, Andrew

    2012-01-01

    Conformity is thought to be an important force in cultural evolution because it has the potential to stabilize cooperation in large groups, potentiate group selection and thus explain uniquely human behaviors...

  9. Determination of absorbed dose in water at the reference point d(r0, theta0) for an 192Ir HDR brachytherapy source using a Fricke system.

    Science.gov (United States)

    Austerlitz, C; Mota, H C; Sempau, J; Benhabib, S M; Campos, D; Allison, R; DeAlmeida, C E; Zhu, D; Sibata, C H

    2008-12-01

    A ring-shaped Fricke device was developed to measure the absolute dose on the transverse bisector of a 192Ir high dose rate (HDR) source at 1 cm from its center in water, D(r0, theta0). It consists of a polymethylmethacrylate (PMMA) rod (axial axis) with a cylindrical cavity at its center to insert the 192Ir radioactive source. A ring cavity around the source with 1.5 mm thickness and 5 mm height is centered at 1 cm from the central axis of the source. This ring cavity is etched in a disk shaped base with 2.65 cm diameter and 0.90 cm thickness. The cavity has a wall around it 0.25 cm thick. This ring is filled with Fricke solution, sealed, and the whole assembly is immersed in water during irradiations. The device takes advantage of the cylindrical geometry to measure D(r0, theta0). Irradiations were performed with a Nucletron microselectron HDR unit loaded with an 192Ir Alpha Omega radioactive source. A Spectronic 1001 spectrophotometer was used to measure the optical absorbance using a 1 mL quartz cuvette with 1.00 cm light pathlength. The PENELOPE Monte Carlo code (MC) was utilized to simulate the Fricke device and the 192Ir Alpha Omega source in detail to calculate the perturbation introduced by the PMMA material. A NIST traceable calibrated well type ionization chamber was used to determine the air-kerma strength, and a published dose-rate constant was used to determine the dose rate at the reference point. The time to deliver 30.00 Gy to the reference point was calculated. This absorbed dose was then compared to the absorbed dose measured by the Fricke solution. Based on MC simulation, the PMMA of the Fricke device increases the D(r0, theta0) by 2.0%. Applying the corresponding correction factor, the D(r0, theta0) value assessed with the Fricke device agrees within 2.0% with the expected value with a total combined uncertainty of 3.43% (k=1). The Fricke device provides a promising method towards calibration of brachytherapy radiation sources in terms of D(r0

  10. EC declaration of conformity.

    Science.gov (United States)

    Donawa, M E

    1996-05-01

    The CE-marking procedure requires that manufacturers draw up a written declaration of conformity before placing their products on the market. However, some companies do not realize that this is a requirement for all devices. Also, there is no detailed information concerning the contents and format of the EC declaration of conformity in the medical device Directives or in EC guidance documentation. This article will discuss some important aspects of the EC declaration of conformity and some of the guidance that is available on its contents and format.

  11. Conformal expansions and renormalons

    CERN Document Server

    Gardi, E; Gardi, Einan; Grunberg, Georges

    2001-01-01

    The large-order behaviour of QCD is dominated by renormalons. On the other hand renormalons do not occur in conformal theories, such as the one describing the infrared fixed-point of QCD at small beta_0 (the Banks--Zaks limit). Since the fixed-point has a perturbative realization, all-order perturbative relations exist between the conformal coefficients, which are renormalon-free, and the standard perturbative coefficients, which contain renormalons. Therefore, an explicit cancellation of renormalons should occur in these relations. The absence of renormalons in the conformal limit can thus be seen as a constraint on the structure of the QCD perturbative expansion. We show that the conformal constraint is non-trivial: a generic model for the large-order behaviour violates it. We also analyse a specific example, based on a renormalon-type integral over the two-loop running-coupling, where the required cancellation does occur.

  12. 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.

  13. Quantum massive conformal gravity

    Energy Technology Data Exchange (ETDEWEB)

    Faria, F.F. [Universidade Estadual do Piaui, Centro de Ciencias da Natureza, Teresina, PI (Brazil)

    2016-04-15

    We first find the linear approximation of the second plus fourth order derivative massive conformal gravity action. Then we reduce the linearized action to separated second order derivative terms, which allows us to quantize the theory by using the standard first order canonical quantization method. It is shown that quantum massive conformal gravity is renormalizable but has ghost states. A possible decoupling of these ghost states at high energies is discussed. (orig.)

  14. 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....

  15. Conformally coupled inflation

    CERN Document Server

    Faraoni, Valerio

    2013-01-01

    A massive scalar field in a curved spacetime can propagate along the light cone, a causal pathology, which can, in principle, be eliminated only if the scalar couples conformally to the Ricci curvature of spacetime. This property mandates conformal coupling for the field driving inflation in the early universe. During slow-roll inflation, this coupling can cause super-acceleration and, as a signature, a blue spectrum of primordial gravitational waves.

  16. Group Size and Conformity

    OpenAIRE

    Bond, Rod

    2005-01-01

    Abstract This paper reviews theory and research on the relationship between group size and conformity and presents a meta-analysis of 125 Asch-type conformity studies. It questions the assumption of a single function made in formal models of social influence and proposes instead that the function will vary depending on which social influence process predominates. It is argued that normative influence is lik...

  17. Conformism and Wealth Distribution

    OpenAIRE

    Mino, Kazuo; Nakamoto, Yasuhiro

    2014-01-01

    This paper explores the role of consumption externalities in a neoclassical growth model in which households have heterogeneous preferences. We fi?nd that the degree of conformism in consumption held by each household signifi?cantly affects the speed of convergence of the aggregate economy as well as the patterns of wealth distribution in the steady state equilibrium. In particular, a higher degree of consumption conformism accelerates the convergence speed of the economy towards the steady s...

  18. Conformally Coupled Inflation

    Directory of Open Access Journals (Sweden)

    Valerio Faraoni

    2013-07-01

    Full Text Available A massive scalar field in a curved spacetime can propagate along the light cone, a causal pathology, which can, in principle, be eliminated only if the scalar couples conformally to the Ricci curvature of spacetime. This property mandates conformal coupling for the field driving inflation in the early universe. During slow-roll inflation, this coupling can cause super-acceleration and, as a signature, a blue spectrum of primordial gravitational waves.

  19. Conformational and structural studies of 1-chloropropane and 1-bromopropane from temperature-dependant FT-IR spectra of rare gas solutions and ab initio calculations

    Science.gov (United States)

    Durig, J. R.; Zhu, X.; Shen, S.

    2001-08-01

    Variable temperature (-55 to -150°C) studies of the infrared spectra (3500-400 cm -1) of 1-chloropropane (CH 3CH 2CH 2Cl) and 1-bromopropane (CH 3CH 2CH 2Br) dissolved in liquid krypton and xenon, respectively, have been recorded. Utilizing two conformer pairs in krypton solution for chloride and three conformer pairs in xenon solution for bromide, enthalpy differences of 52±3 cm -1 (0.62±0.06 kJ/mol) and 72±7 cm -1 (0.86±0.08 kJ/mol) were obtained for the chloride and bromide, respectively, with the gauche form being the more stable conformer for both molecules. From these data, it is estimated that 28 and 26% of trans form are present at ambient temperature for the chloride and bromide, respectively. The conformation stabilities, harmonic force constants, fundamental frequencies, infrared intensities and Raman activities have been obtained from RHF/6-31G(d) and/or MP2/6-31G(d) ab initio calculations for both halopropanes and these quantities have been compared to the experimental values when appropriate. The optimized geometries have also been obtained with several different ab initio basis sets with full electron correlation by the perturbation method up to MP2/6-311+G(2d,2p). The r0 structural parameters of both halopropanes have been obtained by combining the ab initio data with the previously reported microwave rotational constants for both conformers. The quantities are compared to the corresponding results for some similar molecules.

  20. Validation of the memorial Sloan-Kettering Cancer Center nomogram to predict disease-specific survival after R0 resection in a Chinese gastric cancer population.

    Directory of Open Access Journals (Sweden)

    Donglai Chen

    Full Text Available BACKGROUND: Prediction of disease-specific survival (DSS for individual patient with gastric cancer after R0 resection remains a clinical concern. Since the clinicopathologic characteristics of gastric cancer vary widely between China and western countries, this study is to evaluate a nomogram from Memorial Sloan-Kettering Cancer Center (MSKCC for predicting the probability of DSS in patients with gastric cancer from a Chinese cohort. METHODS: From 1998 to 2007, clinical data of 979 patients with gastric cancer who underwent R0 resection were retrospectively collected from Peking University Cancer Hospital & Institute and used for external validation. The performance of the MSKCC nomogram in our population was assessed using concordance index (C-index and calibration plot. RESULTS: The C-index for the MSKCC predictive nomogram was 0.74 in the Chinese cohort, compared with 0.69 for American Joint Committee on Cancer (AJCC staging system (P<0.0001. This suggests that the discriminating value of MSKCC nomogram is superior to AJCC staging system for prognostic prediction in the Chinese population. Calibration plots showed that the actual survival of Chinese patients corresponded closely to the MSKCC nonogram-predicted survival probabilities. Moreover, MSKCC nomogram predictions demonstrated the heterogeneity of survival in stage IIA/IIB/IIIA/IIIB disease of the Chinese patients. CONCLUSION: In this study, we externally validated MSKCC nomogram for predicting the probability of 5- and 9-year DSS after R0 resection for gastric cancer in a Chinese population. The MSKCC nomogram performed well with good discrimination and calibration. The MSKCC nomogram improved individualized predictions of survival, and may assist Chinese clinicians and patients in individual follow-up scheduling, and decision making with regard to various treatment options.

  1. Conformational sampling techniques.

    Science.gov (United States)

    Hatfield, Marcus P D; Lovas, Sándor

    2014-01-01

    The potential energy hyper-surface of a protein relates the potential energy of the protein to its conformational space. This surface is useful in determining the native conformation of a protein or in examining a statistical-mechanical ensemble of structures (canonical ensemble). In determining the potential energy hyper-surface of a protein three aspects must be considered; reducing the degrees of freedom, a method to determine the energy of each conformation and a method to sample the conformational space. For reducing the degrees of freedom the choice of solvent, coarse graining, constraining degrees of freedom and periodic boundary conditions are discussed. The use of quantum mechanics versus molecular mechanics and the choice of force fields are also discussed, as well as the sampling of the conformational space through deterministic and heuristic approaches. Deterministic methods include knowledge-based statistical methods, rotamer libraries, homology modeling, the build-up method, self-consistent electrostatic field, deformation methods, tree-based elimination and eigenvector following routines. The heuristic methods include Monte Carlo chain growing, energy minimizations, metropolis monte carlo and molecular dynamics. In addition, various methods to enhance the conformational search including the deformation or smoothing of the surface, scaling of system parameters, and multi copy searching are also discussed.

  2. Conformation of 1,2-Dimethoxyethane in Water

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    To understand the conformation of 1,2-dimethoxyethane (DME) in water, a system of two kinds of molecules, DME and H2O, was focused. The interaction of various conformers of DME with water was studied by means of ab initio molecular orbital calculation with 6-31G(d)basis set. It is shown that there are two forms of interactions between the two molecules in the sys tem, the close touched (H2O attaches to the two oxygen atoms of DME) and the open touched (H2O attaches to one oxygen atom of DME) structures. The conformation of DME is remark ably influenced by the interactions. Instead the ttt conformer is preferred in the gas state, with a close touched H2O the tgt conformer becomes the most stable one. The obtained hydration ener gies show that the stabilized order of DME conformers by water is tgt>tgg'>ttt.

  3. The basic reproduction number R0 and effectiveness of reactive interventions during dengue epidemics: the 2002 dengue outbreak in Easter Island, Chile.

    Science.gov (United States)

    Chowell, Gerardo; Fuentes, R; Olea, A; Aguilera, X; Nesse, H; Hyman, J M

    2013-01-01

    We use a stochastic simulation model to explore the effect of reactive intervention strategies during the 2002 dengue outbreak in the small population of Easter Island, Chile. We quantified the effect of interventions on the transmission dynamics and epidemic size as a function of the simulated control intensity levels and the timing of initiation of control interventions. Because no dengue outbreaks had been reported prior to 2002 in Easter Island, the 2002 epidemic provided a unique opportunity to estimate the basic reproduction number R0 during the initial epidemic phase, prior to the start of control interventions. We estimated R0 at 27.2 (95%CI: 14.8, 49.3). We found that the final epidemic size is highly sensitive to the timing of start of interventions. However, even when the control interventions start several weeks after the epidemic onset, reactive intervention efforts can have a significant impact on the final epidemic size. Our results indicate that the rapid implementation of control interventions can have a significant effect in reducing the epidemic size of dengue epidemics.

  4. Spin-phonon coupling in epitaxial S r0.6B a0.4Mn O3 thin films

    Science.gov (United States)

    Goian, V.; Langenberg, E.; Marcano, N.; Bovtun, V.; Maurel, L.; Kempa, M.; Prokscha, T.; Kroupa, J.; Algarabel, P. A.; Pardo, J. A.; Kamba, S.

    2017-02-01

    Spin-phonon coupling is investigated in epitaxially strained S r1 -xB axMn O3 thin films with perovskite structure by means of microwave (MW) and infrared (IR) spectroscopy. In this work we focus on the S r0.6B a0.4Mn O3 composition grown on (LaAlO3) 0.3(Sr2AlTaO6 ) 0.7 substrate. The MW complex electromagnetic response shows a decrease in the real part and a clear anomaly in the imaginary part around 150 K. Moreover, it coincides with a 17 % hardening of the lowest-frequency polar phonon seen in IR reflectance spectra. In order to further elucidate this phenomenon, low-energy muon-spin spectroscopy was carried out, signaling the emergence of antiferromagnetic order with Néel temperature (TN) around 150 K. Thus, our results confirm that epitaxial S r0.6B a0.4Mn O3 thin films display strong spin-phonon coupling below TN, which may stimulate further research on tuning the magnetoelectric coupling by controlling the epitaxial strain and chemical pressure in the S r1 -xB axMn O3 system.

  5. Conformal ALON® and spinel windows

    Science.gov (United States)

    Goldman, Lee M.; Smith, Mark; Ramisetty, Mohan; Jha, Santosh; Sastri, Suri

    2017-05-01

    The requirements for modern aircraft based reconnaissance systems are driving the need for conformal windows for future sensor systems. However, limitations on optical systems and the ability to produce windows in complex geometries currently limit the geometry of existing windows and window assemblies to faceted assemblies of flat windows. ALON consists primarily of aluminum and oxygen, similar to that of alumina, with a small amount of nitrogen added to help stabilize the cubic gamma-AlON phase. ALON's chemical similarity to alumina, translates into a robust manufacturing process. This ease of processing has allowed Surmet to produce ALON windows and domes in a wide variety of geometries and sizes. Spinel (MgAl2O4) contains equal molar amounts of MgO and Al2O3, and is a cubic material, that transmits further into the Infrared than ALON. Spinel is produced via powder processing techniques similar to those used to produce ALON. Surmet is now applying the lessons learned with ALON to produce conformal spinel windows and domes as well.

  6. Stability assessment of a moderately conforming all-polyethylene tibial component in total knee arthroplasty: a prospective RSA study with 2 years of follow-up of the Kinemax Plus design.

    Science.gov (United States)

    Adalberth, G; Nilsson, K G; Byström, S; Kolstad, K; Mallmin, H; Milbrink, J

    1999-01-01

    The magnitude and pattern of the migration of an all-polyethylene tibial component with moderately conforming articular surfaces in total knee arthroplasty was analyzed in 20 patients > or =60 years during a 2-year follow-up using radiostereometry (RSA). Most of the migration occurred during the initial 4 months, whereafter the migration diminished, reaching a mean maximum migration of 0.75 mm at 2 years. Similar patterns were found for rotation of the implant. Maximum subsidence at 2 years was 0.7 mm and was most commonly located at the posteromedial part of the tibial component. These results indicate that an all-polyethylene tibial component with moderately conforming articular geometry and with a thickness of 10-12 mm demonstrated migration patterns compatible with a favorable prognosis in regard to future aseptic loosening.

  7. Evolution of Conformity in Social Dilemmas.

    Directory of Open Access Journals (Sweden)

    Yali Dong

    Full Text Available People often deviate from their individual Nash equilibrium strategy in game experiments based on the prisoner's dilemma (PD game and the public goods game (PGG, whereas conditional cooperation, or conformity, is supported by the data from these experiments. In a complicated environment with no obvious "dominant" strategy, conformists who choose the average strategy of the other players in their group could be able to avoid risk by guaranteeing their income will be close to the group average. In this paper, we study the repeated PD game and the repeated m-person PGG, where individuals' strategies are restricted to the set of conforming strategies. We define a conforming strategy by two parameters, initial action in the game and the influence of the other players' choices in the previous round. We are particularly interested in the tit-for-tat (TFT strategy, which is the well-known conforming strategy in theoretical and empirical studies. In both the PD game and the PGG, TFT can prevent the invasion of non-cooperative strategy if the expected number of rounds exceeds a critical value. The stability analysis of adaptive dynamics shows that conformity in general promotes the evolution of cooperation, and that a regime of cooperation can be established in an AllD population through TFT-like strategies. These results provide insight into the emergence of cooperation in social dilemma games.

  8. Evolution of Conformity in Social Dilemmas.

    Science.gov (United States)

    Dong, Yali; Li, Cong; Tao, Yi; Zhang, Boyu

    2015-01-01

    People often deviate from their individual Nash equilibrium strategy in game experiments based on the prisoner's dilemma (PD) game and the public goods game (PGG), whereas conditional cooperation, or conformity, is supported by the data from these experiments. In a complicated environment with no obvious "dominant" strategy, conformists who choose the average strategy of the other players in their group could be able to avoid risk by guaranteeing their income will be close to the group average. In this paper, we study the repeated PD game and the repeated m-person PGG, where individuals' strategies are restricted to the set of conforming strategies. We define a conforming strategy by two parameters, initial action in the game and the influence of the other players' choices in the previous round. We are particularly interested in the tit-for-tat (TFT) strategy, which is the well-known conforming strategy in theoretical and empirical studies. In both the PD game and the PGG, TFT can prevent the invasion of non-cooperative strategy if the expected number of rounds exceeds a critical value. The stability analysis of adaptive dynamics shows that conformity in general promotes the evolution of cooperation, and that a regime of cooperation can be established in an AllD population through TFT-like strategies. These results provide insight into the emergence of cooperation in social dilemma games.

  9. Boundary Conformal Field Theory

    CERN Document Server

    Cardy, J L

    2004-01-01

    Boundary conformal field theory (BCFT) is simply the study of conformal field theory (CFT) in domains with a boundary. It gains its significance because, in some ways, it is mathematically simpler: the algebraic and geometric structures of CFT appear in a more straightforward manner; and because it has important applications: in string theory in the physics of open strings and D-branes, and in condensed matter physics in boundary critical behavior and quantum impurity models. In this article, however, I describe the basic ideas from the point of view of quantum field theory, without regard to particular applications nor to any deeper mathematical formulations.

  10. Conformal field theory

    CERN Document Server

    Ketov, Sergei V

    1995-01-01

    Conformal field theory is an elegant and powerful theory in the field of high energy physics and statistics. In fact, it can be said to be one of the greatest achievements in the development of this field. Presented in two dimensions, this book is designed for students who already have a basic knowledge of quantum mechanics, field theory and general relativity. The main idea used throughout the book is that conformal symmetry causes both classical and quantum integrability. Instead of concentrating on the numerous applications of the theory, the author puts forward a discussion of the general

  11. Complex magnetic phase diagram with multistep spin-flop transitions in L a0.25P r0.75C o2P2

    Science.gov (United States)

    Tan, Xiaoyan; Garlea, V. Ovidiu; Kovnir, Kirill; Thompson, Corey M.; Xu, Tongshuai; Cao, Huibo; Chai, Ping; Tener, Zachary P.; Yan, Shishen; Xiong, Peng; Shatruk, Michael

    2017-01-01

    L a0.25P r0.75C o2P2 crystallizes in the tetragonal ThC r2S i2 structure type and shows multiple magnetic phase transitions driven by changes in temperature and magnetic field. The nature of these transitions was investigated by a combination of magnetic and magnetoresistance measurements and both single crystal and powder neutron diffraction. The Co magnetic moments order ferromagnetically (FM) parallel to the c axis at 282 K, followed by antiferromagnetic (AFM) ordering at 225 K. In the AFM structure, the Co magnetic moments align along the c axis with FM [C o2P2] layers arranged in an alternating sequence, ↑↑↓↓ , which leads to the doubling of the c axis in the magnetic unit cell. Another AFM transition is observed at 27 K, due to the ordering of a half of Pr moments in the a b plane. The other half of Pr moments undergoes AFM ordering along the c axis at 11 K, causing simultaneous reorientation of the previously ordered Pr moments into an AFM structure with the moments being canted with respect to the c axis. This AFM transition causes an abrupt decrease in electrical resistivity at 11 K. Under applied magnetic field, two metamagnetic transitions are observed in the Pr sublattice at 0.8 and 5.4 T. They correlate with two anomalies in magnetoresistance measurements at the same critical fields. A comparison of the temperature- and field-dependent magnetic properties of L a0.25P r0.75C o2P2 to the magnetic behavior of PrC o2P2 is provided.

  12. Data Qualification Report For: Thermodynamic Data File, DATA0.YMP.R0 For Geochemical Code, EQ3/6 

    Energy Technology Data Exchange (ETDEWEB)

    P.L. Cloke

    2001-10-16

    The objective of this work is to evaluate the adequacy of chemical thermodynamic data provided by Lawrence Livermore National Laboratory (LLNL) as DataO.ymp.ROA in response to an input request submitted under AP-3.14Q. This request specified that chemical thermodynamic data available in the file, Data0.com.R2, be updated, improved, and augmented for use in geochemical modeling used in Process Model Reports (PMRs) for Engineered Barrier Systems, Waste Form, Waste Package, Unsaturated Zone, and Near Field Environment, as well as for Performance Assessment. The data are qualified in the temperature range 0 to 100 C. Several Data Tracking Numbers (DTNs) associated with Analysis/Model Reports (AMR) addressing various aspects of the post-closure chemical behavior of the waste package and the Engineered Barrier System that rely on EQ316 outputs to which these data are used as input, are Principal Factor affecting. This qualification activity was accomplished in accordance with the AP-SIII.2Q using the Technical Assessment method. A development plan, TDP-EBS-MD-000044, was prepared in accordance with AP-2.13Q and approved by the Responsible Manager. In addition, a Process Control Evaluation was performed in accordance with AP-SV.1Q. The qualification method, selected in accordance with AP-SIII.2Q, was Technical Assessment. The rationale for this approach is that the data in File Data0.com.R2 are considered Handbook data and therefore do not themselves require qualification. Only changes to Data0.com.R2 required qualification. A new file has been produced which contains the database Data0.ymp.R0, which is recommended for qualification as a result of this action. Data0.ymp.R0 will supersede Data0.com.R2 for all Yucca Mountain Project (YMP) activities.

  13. Malaria's missing number: calculating the human component of R0 by a within-host mechanistic model of Plasmodium falciparum infection and transmission.

    Directory of Open Access Journals (Sweden)

    Geoffrey L Johnston

    2013-04-01

    Full Text Available Human infection by malarial parasites of the genus Plasmodium begins with the bite of an infected Anopheles mosquito. Current estimates place malaria mortality at over 650,000 individuals each year, mostly in African children. Efforts to reduce disease burden can benefit from the development of mathematical models of disease transmission. To date, however, comprehensive modeling of the parameters defining human infectivity to mosquitoes has remained elusive. Here, we describe a mechanistic within-host model of Plasmodium falciparum infection in humans and pathogen transmission to the mosquito vector. Our model incorporates the entire parasite lifecycle, including the intra-erythrocytic asexual forms responsible for disease, the onset of symptoms, the development and maturation of intra-erythrocytic gametocytes that are transmissible to Anopheles mosquitoes, and human-to-mosquito infectivity. These model components were parameterized from malaria therapy data and other studies to simulate individual infections, and the ensemble of outputs was found to reproduce the full range of patient responses to infection. Using this model, we assessed human infectivity over the course of untreated infections and examined the effects in relation to transmission intensity, expressed by the basic reproduction number R0 (defined as the number of secondary cases produced by a single typical infection in a completely susceptible population. Our studies predict that net human-to-mosquito infectivity from a single non-immune individual is on average equal to 32 fully infectious days. This estimate of mean infectivity is equivalent to calculating the human component of malarial R0 . We also predict that mean daily infectivity exceeds five percent for approximately 138 days. The mechanistic framework described herein, made available as stand-alone software, will enable investigators to conduct detailed studies into theories of malaria control, including the effects of

  14. CONFORMANCE IMPROVEMENT USING GELS

    Energy Technology Data Exchange (ETDEWEB)

    Randall S. Seright

    2003-09-01

    This report describes work performed during the second year of the project, ''Conformance Improvement Using Gels.'' The project has two objectives. The first objective is to identify gel compositions and conditions that substantially reduce flow through fractures that allow direct channeling between wells, while leaving secondary fractures open so that high fluid injection and production rates can be maintained. The second objective is to optimize treatments in fractured production wells, where the gel must reduce permeability to water much more than that to oil. Pore-level images from X-ray computed microtomography were re-examined for Berea sandstone and porous polyethylene. This analysis suggests that oil penetration through gel-filled pores occurs by a gel-dehydration mechanism, rather than a gel-ripping mechanism. This finding helps to explain why aqueous gels can reduce permeability to water more than to oil. We analyzed a Cr(III)-acetate-HPAM gel treatment in a production well in the Arbuckle formation. The availability of accurate pressure data before, during, and after the treatment was critical for the analysis. After the gel treatment, water productivity was fairly constant at about 20% of the pre-treatment value. However, oil productivity was stimulated by a factor of 18 immediately after the treatment. During the six months after the treatment, oil productivity gradually decreased to approach the pre-treatment value. To explain this behavior, we proposed that the fracture area open to oil flow was increased substantially by the gel treatment, followed by a gradual closing of the fractures during subsequent production. For a conventional Cr(III)-acetate-HPAM gel, the delay between gelant preparation and injection into a fracture impacts the placement, leakoff, and permeability reduction behavior. Formulations placed as partially formed gels showed relatively low pressure gradients during placement, and yet substantially reduced the

  15. A CONFORMATIONAL ELASTICITY THEORY

    Institute of Scientific and Technical Information of China (English)

    1998-01-01

    A new statistical theory based on the rotational isomeric state model describing the chain conformational free energy has been proposed. This theory can be used to predict different tensions of rubber elongation for chemically different polymers, and the energy term during the elongation of natural rubber coincides with the experimental one.

  16. Conformal cloak for waves

    CERN Document Server

    Chen, Huanyang; Tyc, Tomas

    2011-01-01

    Conformal invisibility devices are only supposed to work within the validity range of geometrical optics. Here we show by numerical simulations and analytical arguments that for certain quantized frequencies they are nearly perfect even in a regime that clearly violates geometrical optics. The quantization condition follows from the analogy between the Helmholtz equation and the stationary Schrodinger equation.

  17. Conformal supermultiplets without superpartners

    CERN Document Server

    Jarvis, Peter

    2011-01-01

    We consider polynomial deformations of Lie superalgebras and their representations. For the class A(n-1,0) ~ sl(n/1), we identify families of superalgebras of quadratic and cubic type, consistent with Jacobi identities. For such deformed superalgebras we point out the possibility of zero step supermultiplets, carried on a single, irreducible representation of the even (Lie) subalgebra. For the conformal group SU(2,2) in 1+3-dimensional spacetime, such irreducible (unitary) representations correspond to standard conformal fields (j_1,j_2;d), where (j_1,j_2) is the spin and d the conformal dimension; in the massless class j_1 j_2=0, and d=j_1+j_2+1. We show that these repesentations are zero step supermultiplets for the superalgebra SU_(2)(2,2/1), the quadratic deformation of conformal supersymmetry SU(2,2/1). We propose to elevate SU_(2)(2,2/1) to a symmetry of the S-matrix. Under this scenario, low-energy standard model matter fields (leptons, quarks, Higgs scalars and gauge fields) descended from such confor...

  18. Conformal General Relativity

    CERN Document Server

    Pervushin, V

    2001-01-01

    The inflation-free solution of problems of the modern cosmology (horizon, cosmic initial data, Planck era, arrow of time, singularity,homogeneity, and so on) is considered in the conformal-invariant unified theory given in the space with geometry of similarity where we can measure only the conformal-invariant ratio of all quantities. Conformal General Relativity is defined as the $SU_c(3)\\times SU(2)\\times U(1)$-Standard Model where the dimensional parameter in the Higgs potential is replaced by a dilaton scalar field described by the negative Penrose-Chernikov-Tagirov action. Spontaneous SU(2) symmetry breaking is made on the level of the conformal-invariant angle of the dilaton-Higgs mixing, and it allows us to keep the structure of Einstein's theory with the equivalence principle. We show that the lowest order of the linearized equations of motion solves the problems mentioned above and describes the Cold Universe Scenario with the constant temperature T and z-history of all masses with respect to an obser...

  19. Conformational changes in biopolymers

    Science.gov (United States)

    Ivanov, Vassili

    2005-12-01

    Biopolymer conformational changes are involved in many biological processes. This thesis summarizes some theoretical and experimental approaches which I have taken at UCLA to explore conformational changes in biopolymers. The reversible thermal denaturation of the DNA double helix is, perhaps, the simplest example of biopolymer conformational change. I have developed a statistical mechanics model of DNA melting with reduced degrees of freedom, which allows base stacking interaction to be taken into account and treat base pairing and stacking separately. Unlike previous models, this model describes both the unpairing and unstacking parts of the experimental melting curves and explains the observed temperature dependence of the effective thermodynamic parameters used in models of the nearest neighbor type. I developed a basic kinetic model for irreversible thermal denaturation of F-actin, which incorporates depolymerization of F-actin from the ends and breaking of F-actin fiber in the middle. The model explains the cooperativity of F-actin thermal denaturation observed by D. Pavlov et al. in differential calorimetry measurements. CG-rich DNA sequences form left-handed Z-DNA at high ionic strength or upon binding of polyvalent ions and some proteins. I studied experimentally the B-to-Z transition of the (CG)6 dodecamer. Improvement of the locally linearized model used to interpret the data gives evidence for an intermediate state in the B-to-Z transition of DNA, contrary to previous research on this subject. In the past 15 years it has become possible to study the conformational changes of biomolecules using single-molecule techniques. In collaboration with other lab members I performed a single-molecule experiment, where we monitored the displacement of a micrometer-size bead tethered to a surface by a DNA probe undergoing the conformational change. This technique allows probing of conformational changes with subnanometer accuracy. We applied the method to detect

  20. Relationship between core stability, functional movement, and performance.

    Science.gov (United States)

    Okada, Tomoko; Huxel, Kellie C; Nesser, Thomas W

    2011-01-01

    The purpose of this study was to determine the relationship between core stability, functional movement, and performance. Twenty-eight healthy individuals (age = 24.4 ± 3.9 yr, height = 168.8 ± 12.5 cm, mass = 70.2 ± 14.9 kg) performed several tests in 3 categories: core stability (flexion [FLEX], extension [EXT], right and left lateral [LATr/LATl]), functional movement screen (FMS) (deep squat [DS], trunk-stability push-up [PU], right and left hurdle step [HSr/HSl], in-line lunge [ILLr/ILLl], shoulder mobility [SMr/SMl], active straight leg raise [ASLRr/ASLRl], and rotary stability [RSr/RSl]), and performance tests (backward medicine ball throw [BOMB], T-run [TR], and single leg squat [SLS]). Statistical significance was set at p ≤ 0.05. There were significant correlations between SLS and FLEX (r = 0.500), LATr (r = 0.495), and LATl (r = 0.498). The TR correlated significantly with both LATr (r = 0.383) and LATl (r = 0.448). Of the FMS, BOMB was significantly correlated with HSr (r = 0.415), SMr (r = 0.388), PU (r = 0.407), and RSr (r = 0.391). The TR was significantly related with HSr (r = 0.518), ILLl (r = 0.462) and SMr (r = 0.392). The SLS only correlated significantly with SMr (r = 0.446). There were no significant correlations between core stability and FMS. Moderate to weak correlations identified suggest core stability and FMS are not strong predictors of performance. In addition, existent assessments do not satisfactorily confirm the importance of core stability on functional movement. Despite the emphasis fitness professionals have placed on functional movement and core training for increased performance, our results suggest otherwise. Although training for core and functional movement are important to include in a fitness program, especially for injury prevention, they should not be the primary emphasis of any training program.

  1. Dynamics in the Charged Time Conformal Schwarzschild Black Hole

    CERN Document Server

    Jawad, Abdul; Shahzad, M Umair; Abbas, G

    2016-01-01

    In this work, we present the new technique for discussing the dynamical motion of neutral as well as charged particles in the absence/presence of magnetic field around the time conformal Schwarzschild black hole. Initially, we find the numerical solutions of geodesics of Schwarzschild black hole and the time conformal Schwarzschild black hole. We observe that the Schwarzschild spacetime admits the time conformal factor $e^{\\epsilon f(t)}$, where $f(t)$ is an arbitrary function and $\\epsilon$ is very small which causes the perturbation in the spacetimes. This technique also re-scale the energy content of spacetime. We also investigate the thermal stability, horizons and energy conditions corresponding time conformal Schwarzschild spacetime. Also, we examine the dynamics of neutral and charged particle around time conformal Schwarzschild black hole. We investigate the circumstances under which the particle can escape from vicinity of black hole after collision with another particle. We analyze the effective pot...

  2. A Conformal Extension Theorem based on Null Conformal Geodesics

    CERN Document Server

    Lübbe, Christian

    2008-01-01

    In this article we describe the formulation of null geodesics as null conformal geodesics and their description in the tractor formalism. A conformal extension theorem through an isotropic singularity is proven by requiring the boundedness of the tractor curvature and its derivatives to sufficient order along a congruence of null conformal geodesic. This article extends earlier work by Tod and Luebbe.

  3. Seven Conformers of Pipecolic Acid Identified in the Gas Phase

    Science.gov (United States)

    Cabezas, Carlos; Simao, Alcides; Alonso, José L.

    2016-06-01

    The multiconformational landscape of the non-proteinogenic cyclic amino acid pipecolic acid has been explored in the gas phase. Solid pipecolic acid (m.p. 280°C) was vaporized by laser ablation (LA) and expanded in a supersonic jet where the rotational spectra of seven conformers were obtained by broadband microwave spectroscopy (CP-FTMW). All conformers were conclusively identified by comparison of the experimental spectroscopic constants with those predicted theoretically. The relative stability of the conformers rests on a delicate balance of the different intramolecular hydrogen bonds established between the carboxylic and the amino groups.

  4. Conformal continuations and wormhole instability in scalar-tensor gravity

    CERN Document Server

    Bronnikov, K A

    2004-01-01

    We study the stability of static, spherically symmetric, traversable wormholes existing due to conformal continuations in a class of scalar-tensor theories with zero scalar field potential (so that Fisher's well-known scalar-vacuum solution holds in the Einstein conformal frame). Specific examples of such wormholes are those with nonminimally (e.g., conformally) coupled scalar fields. All boundary conditions for scalar and metric perturbations are taken into account. All such wormholes are shown to be unstable under spherically symmetric perturbations. The instability is proved analytically with the aid of the theory of self-adjoint operators in Hilbert space and is confirmed by a numerical computation.

  5. 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.

  6. From integrable to conformal theory

    Energy Technology Data Exchange (ETDEWEB)

    Babelon, O. (Paris-6 Univ., 75 (France). Lab. de Physique Theorique et Hautes Energies)

    1990-12-01

    Working in the context of Toda field theory, we establish the relationship between their integrability properties and their conformal structure, thereby clarifying the role of the Yang-Baxter equation in conformal field theory. (orig.).

  7. On conformal lenses

    CERN Document Server

    Chen, Huanyang; Li, Hui

    2011-01-01

    Plane mirror can make one object into two for observers on the object's side. Yet, there seems no way to achieve the same effect for observers from all directions. In this letter, we will design a new class of gradient index lenses from multivalued optical conformal mapping. We shall call them the conformal lenses. Such lenses can transform one source into two (or even many) omnidirectionally. Like the overlapped illusion optics does, they can even transform multiple sources into one. Rather than using negative index materials, implementation here only needs isotropic positive index materials like other gradient index lenses. One obvious drawback however, is that they have singular permittivity values which restrict them to functioning at one single frequency. This however, needs not be the case when applying transmutation methods, which enable the lenses to work in a broadband frequency range.

  8. Multiscale conformal pattern transfer

    Science.gov (United States)

    Lodewijks, Kristof; Miljkovic, Vladimir; Massiot, Inès; Mekonnen, Addis; Verre, Ruggero; Olsson, Eva; Dmitriev, Alexandre

    2016-06-01

    We demonstrate a method for seamless transfer from a parent flat substrate of basically any lithographic top-down or bottom-up pattern onto essentially any kind of surface. The nano- or microscale patterns, spanning macroscopic surface areas, can be transferred with high conformity onto a large variety of surfaces when such patterns are produced on a thin carbon film, grown on top of a sacrificial layer. The latter allows lifting the patterns from the flat parent substrate onto a water-air interface to be picked up by the host surface of choice. We illustrate the power of this technique by functionalizing broad range of materials including glass, plastics, metals, rough semiconductors and polymers, highlighting the potential applications in in situ colorimetry of the chemistry of materials, anti-counterfeit technologies, biomolecular and biomedical studies, light-matter interactions at the nanoscale, conformal photovoltaics and flexible electronics.

  9. 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.

  10. Conformal Complementarity Maps

    CERN Document Server

    Barbón, José L F

    2013-01-01

    We study quantum cosmological models for certain classes of bang/crunch singularities, using the duality between expanding bubbles in AdS with a FRW interior cosmology and perturbed CFTs on de Sitter space-time. It is pointed out that horizon complementarity in the AdS bulk geometries is realized as a conformal transformation in the dual deformed CFT. The quantum version of this map is described in full detail in a toy model involving conformal quantum mechanics. In this system the complementarity map acts as an exact duality between eternal and apocalyptic Hamiltonian evolutions. We calculate the commutation relation between the Hamiltonians corresponding to the different frames. It vanishes only on scale invariant states.

  11. 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....

  12. Differential steric effects in Cl reactions with aligned CHD3(v1 = 1) by the R(0) and Q(1) transitions. II. Abstracting the unexcited D-atoms

    Science.gov (United States)

    Wang, Fengyan; Liu, Kopin

    2016-10-01

    A complete set of four polarization-dependent differential cross sections in the reactions of Cl + aligned-CHD 3 ( v 1 = 1 , |" separators=" jK > ) → DCl ( v = 0 ) + CHD 2 ( v 1 = 1 ) is reported here for two different, rotationally polarized states with j = 1: specifically the |" separators=" jK > = |" separators=" 10 > state prepared via the R(0) excitation and the |" separators=" 1 ± 1 > state via Q(1). In stark contrast to the complicated situation of the HCl(v) + CD3(v = 0) channel reported in Paper-I, the stereo-requirement of this isotopic channel for both polarized reactants appears quite straightforward and consistent with a direct rebound mechanism. The extent of steric effects is moderate and relatively smaller than the alternative H-atom abstraction channel. All major findings reported here can qualitatively be understood by first noting that the present reaction invokes abstracting a D-atom, which is the spectator in the IR-excitation process. Next, it is recognized that the directional properties of two polarized states of CHD 3 ( v 1 = 1 , |" separators=" jK > ) should manifest primarily in the IR-excited C-H bond, leaving secondary imprints in the unexcited CD3-moiety. The stereo-specificity of the DCl + CHD2 product channel is further reduced by the fact that the abstraction can occur with any one of the three spatially distinct D-atoms.

  13. Two Additional Remarks on Conformism

    OpenAIRE

    Schlicht, Ekkehart

    2014-01-01

    Abstract This note offers two comments on the article “Social Influences towards Conformism in Economic Experiments” by Hargreaves Heap that is to appear in the Economics e-Journal. One relates to the concept of conformism, the other lines out some phenomena where an explicit recognition of group processes, such as conformism, may be analytically helpful.

  14. Gas Phase Conformations of Tetrapeptide Glycine-Phenylalanine-Glycine-Glycine

    Institute of Scientific and Technical Information of China (English)

    Hui-bin Chen; Yao Wang; Xin Chen; Zi-jing Lin

    2012-01-01

    Systematic search of the potential energy surface of tetrapeptide glycine-phenylalanineglycine-glycine (GFGG) in gas phase is conducted by a combination of PM3,HF and BHandHLYP methods.The conformational search method is described in detail.The relative electronic energies,zero point vibrational energies,dipole moments,rotational constants,vertical ionization energies and the temperature.dependent conformational distributions for a number of important conformers are obtained.The structural characteristics of these conformers are analyzed and it is found that the entropic effect is a dominating factor in determining the relative stabilities of the conformers.The measurements of dipole moments and some characteristic IR mode are shown to be effective approaches to verify the theoretical prediction.The structures of the low energy GFGG conformers are also analyzed in their connection with the secondary structures of proteins.Similarity between the local structures of low energy GFGG conformers and the α-helix is discussed and manyβ- and γ-turn local structures in GFGG conformers are found.

  15. Determination of conformational entropy of fully and partially folded conformations of holo- and apomyoglobin.

    Science.gov (United States)

    Stadler, Andreas M; Koza, Michael Marek; Fitter, Jörg

    2015-01-08

    Holo- and apomyoglobin can be stabilized in native folded, partially folded molten globules (MGs) and denatured states depending on the solvent composition. Although the protein has been studied as a model system in the field of protein folding, little is known about the internal dynamics of the different structural conformations on the picosecond time scale. In a comparative experimental study we investigated the correlation between protein folding and dynamics on the picosecond time scale using incoherent quasielastic neutron scattering (QENS). The measured mean square displacements (MSDs) of conformational motions depend significantly on the secondary structure content of the protein, whereas the correlation times of the observed internal dynamics were found to be similar irrespective of the degree of folding. The conformational entropy difference ΔSconf between the folded conformations and the acid denatured state could be determined from the measured MSDs and was compared to the entropy difference ΔS obtained from thermodynamic parameters reported in the literature. The observed difference between ΔS and ΔSconf was attributed to the entropy difference ΔShydr of dynamically disordered water molecules of the hydration shell. The entropy content of the hydration water is significantly larger in the native folded proteins than in the partially folded MGs. We demonstrate the potential of incoherent neutron scattering for the investigation of the role of conformational dynamics in protein folding.

  16. OSI Conformance Testing for Bibliographic Applications.

    Science.gov (United States)

    Arbez, Gilbert; Swain, Leigh

    1990-01-01

    Describes the development of Open Systems Interconnection (OSI) conformance testing sites, conformance testing tools, and conformance testing services. Discusses related topics such as interoperability testing, arbitration testing, and international harmonization of conformance testing. A glossary is included. (24 references) (SD)

  17. Leaf growth is conformal

    CERN Document Server

    Alim, Karen; Shraiman, Boris I; Boudaoud, Arezki

    2016-01-01

    Growth pattern dynamics lie at the heart of morphogenesis. Here, we investigate the growth of plant leaves. We compute the conformal transformation that maps the contour of a leaf at a given stage onto the contour of the same leaf at a later stage. Based on the mapping we predict the local displacement field in the leaf blade and find it to agree with the experimentally measured displacement field to 92%. This approach is applicable to any two-dimensional system with locally isotropic growth, enabling the deduction of the whole growth field just from observation of the tissue contour.

  18. 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 ...... 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....

  19. Leaf growth is conformal

    Science.gov (United States)

    Alim, Karen; Armon, Shahaf; Shraiman, Boris I.; Boudaoud, Arezki

    2016-10-01

    Growth pattern dynamics lie at the heart of morphogenesis. Here, we investigate the growth of plant leaves. We compute the conformal transformation that maps the contour of a leaf at a given stage onto the contour of the same leaf at a later stage. Based on the mapping we predict the local displacement field in the leaf blade and find it to agree with the experimentally measured displacement field to 92%. This approach is applicable to any two-dimensional system with locally isotropic growth, enabling the deduction of the whole growth field just from observation of the tissue contour.

  20. Conformal fluid dynamics

    CERN Document Server

    Jarvis, P D

    2006-01-01

    We present a conformal theory of a dissipationless relativistic fluid in 2 space-time dimensions. The theory carries with it a representation of the algebra of 2-$D$ area-preserving diffeomorphisms in the target space of the complex scalar potentials. A complete canonical description is given, and the central charge of the current algebra is calculated. The passage to the quantum theory is discussed in some detail; as a result of operator ordering problems, full quantization at the level of the fields is as yet an open problem.

  1. 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

  2. Conformal invariant saturation

    CERN Document Server

    Navelet, H

    2002-01-01

    We show that, in onium-onium scattering at (very) high energy, a transition to saturation happens due to quantum fluctuations of QCD dipoles. This transition starts when the order alpha^2 correction of the dipole loop is compensated by its faster energy evolution, leading to a negative interference with the tree level amplitude. After a derivation of the the one-loop dipole contribution using conformal invariance of the elastic 4-gluon amplitude in high energy QCD, we obtain an exact expression of the saturation line in the plane (Y,L) where Y is the total rapidity and L, the logarithm of the onium scale ratio. It shows universal features implying the Balitskyi - Fadin - Kuraev - Lipatov (BFKL) evolution kernel and the square of the QCD triple Pomeron vertex. For large L, only the higher BFKL Eigenvalue contributes, leading to a saturation depending on leading log perturbative QCD characteristics. For initial onium scales of same order, however, it involves an unlimited summation over all conformal BFKL Eigen...

  3. Hot Conformal Gauge Theories

    CERN Document Server

    Mojaza, Matin; Sannino, Francesco

    2010-01-01

    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 show that the reduced free energy changes sign, at the second, fifth and sixth order in the coupling, when decreasing the number of flavors from the upper end of the conformal window. If the change in sign is interpreted as signal of an instability of the system then we infer a critical number of flavors. Surprisingly this number, if computed to the order g^2, agrees with previous predictions for the lower boundary o...

  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. Spontaneous symmetry breaking in 5D conformally invariant gravity

    CERN Document Server

    Moon, Taeyoon

    2016-01-01

    We explore the possibility of the spontaneous symmetry breaking in 5D conformally invariant gravity, whose action consists of a scalar field nonminimally coupled to the curvature with its potential. Performing dimensional reduction via ADM decomposition, we find that the model allows an exact solution giving rise to the 4D Minkowski vacuum. Exploiting the conformal invariance with Gaussian warp factor, we show that it also admits a solution which implement the spontaneous breaking of conformal symmetry. We investigate its stability by performing the tensor perturbation and find the resulting system is described by the conformal quantum mechanics. Possible applications to the spontaneous symmetry breaking of time-translational symmetry along the dynamical fifth direction and the brane-world scenario are discussed.

  6. Conformational thermodynamics of metal-ion binding to a protein

    Science.gov (United States)

    Das, Amit; Chakrabarti, J.; Ghosh, Mahua

    2013-08-01

    Conformational changes in proteins induced by metal-ions play extremely important role in various cellular processes and technological applications. Dihedral angles are suitable conformational variables to describe microscopic conformations of a biomacromolecule. Here, we use the histograms of the dihedral angles to study the thermodynamics of conformational changes of a protein upon metal-ion binding. Our method applied to Ca2+ ion binding to an important metalloprotein, Calmodulin, reveals different thermodynamic changes in different metal-binding sites. The ligands coordinating to Ca2+ ions also play different roles in stabilizing the metal-ion coordinated protein-structure. Metal-ion binding induce remarkable thermodynamic changes in distant part of the protein via modification of secondary structural elements.

  7. Subtleties Concerning Conformal Tractor Bundles

    CERN Document Server

    Graham, C Robin

    2012-01-01

    The realization of tractor bundles as associated bundles in conformal geometry is studied. It is shown that different natural choices of principal bundle with normal Cartan connection corresponding to a given conformal manifold can give rise to topologically distinct associated tractor bundles for the same inducing representation. Consequences for homogeneous models and conformal holonomy are described. A careful presentation is made of background material concerning standard tractor bundles and equivalence between parabolic geometries and underlying structures.

  8. Dimensional Reduction for Conformal Blocks

    CERN Document Server

    Hogervorst, Matthijs

    2016-01-01

    We consider the dimensional reduction of a CFT, breaking multiplets of the d-dimensional conformal group SO(d+1,1) up into multiplets of SO(d,1). This leads to an expansion of d-dimensional conformal blocks in terms of blocks in d-1 dimensions. In particular, we obtain a formula for 3d conformal blocks as an infinite sum over 2F1 hypergeometric functions with closed-form coefficients.

  9. Loop Virasoro Lie conformal algebra

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-01-15

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

  10. Conformal frames in cosmology

    CERN Document Server

    Domènech, Guillem

    2016-01-01

    From higher dimensional theories, e.g. string theory, one expects the presence of non-minimally coupled scalar fields. We review the notion of conformal frames in cosmology and emphasize their physical equivalence, which holds at least at a classical level. Furthermore, if there is a field, or fields, which dominates the universe, as it is often the case in cosmology, we can use such notion of frames to treat our system, matter and gravity, as two different sectors. On one hand, the gravity sector which describes the dynamics of the geometry and on the other hand the matter sector which has such geometry as a playground. We use this interpretation to build a model where the fact that a curvaton couples to a particular frame metric could leave an imprint in the CMB.

  11. Reflections on Conformal Spectra

    CERN Document Server

    Kim, Hyungrok; Ooguri, Hirosi

    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 $\\Delta_0$ 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 $\\Delta_0$ as well as for large $\\Delta_0$. 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.

  12. Reflections on Conformal Spectra

    CERN Document Server

    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

  13. Conformational changes in DNA gyrase revealed by limited proteolysis

    DEFF Research Database (Denmark)

    Kampranis, S C; Maxwell, A

    1998-01-01

    -induced dimerization of the B subunits is a key step of the gyrase mechanism. The proteolytic fingerprint of this conformation (stabilized by the non-hydrolyzable ATP analog 5'-adenylyl-beta, gamma-imidodiphosphate (ADPNP) shows a protection of the 43-kDa N-terminal domain of the B subunit. The presence of quinolones...

  14. Compact conformations of human protein disulfide isomerase.

    Directory of Open Access Journals (Sweden)

    Shang Yang

    Full Text Available Protein disulfide isomerase (PDI composed of four thioredoxin-like domains a, b, b', and a', is a key enzyme catalyzing oxidative protein folding in the endoplasmic reticulum. Large scale molecular dynamics simulations starting from the crystal structures of human PDI (hPDI in the oxidized and reduced states were performed. The results indicate that hPDI adopts more compact conformations in solution than in the crystal structures, which are stabilized primarily by inter-domain interactions, including the salt bridges between domains a and b' observed for the first time. A prominent feature of the compact conformations is that the two catalytic domains a and a' can locate close enough for intra-molecular electron transfer, which was confirmed by the characterization of an intermediate with a disulfide between the two domains. Mutations, which disrupt the inter-domain interactions, lead to decreased reductase activity of hPDI. Our molecular dynamics simulations and biochemical experiments reveal the intrinsic conformational dynamics of hPDI and its biological impact.

  15. C-terminal helical domains of dengue virus type 4 E protein affect the expression/stability of prM protein and conformation of prM and E proteins.

    Directory of Open Access Journals (Sweden)

    Wen-Yang Tsai

    Full Text Available BACKGROUND: The envelope (E protein of dengue virus (DENV is the major immunogen for dengue vaccine development. At the C-terminus are two α-helices (EH1 and EH2 and two transmembrane domains (ET1 and ET2. After synthesis, E protein forms a heterodimer with the precursor membrane (prM protein, which has been shown as a chaperone for E protein and could prevent premature fusion of E protein during maturation. Recent reports of enhancement of DENV infectivity by anti-prM monoclonal antibodies (mAbs suggest the presence of prM protein in dengue vaccine is potentially harmful. A better understanding of prM-E interaction and its effect on recognition of E and prM proteins by different antibodies would provide important information for future design of safe and effective subunit dengue vaccines. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we examined a series of C-terminal truncation constructs of DENV4 prME, E and prM. In the absence of E protein, prM protein expressed poorly. In the presence of E protein, the expression of prM protein increased in a dose-dependent manner. Radioimmunoprecipitation, sucrose gradient sedimentation and pulse-chase experiments revealed ET1 and EH2 were involved in prM-E interaction and EH2 in maintaining the stability of prM protein. Dot blot assay revealed E protein affected the recognition of prM protein by an anti-prM mAb; truncation of EH2 or EH1 affected the recognition of E protein by several anti-E mAbs, which was further verified by capture ELISA. The E protein ectodomain alone can be recognized well by all anti-E mAbs tested. CONCLUSIONS/SIGNIFICANCE: A C-terminal domain (EH2 of DENV E protein can affect the expression and stability of its chaperone prM protein. These findings not only add to our understanding of the interaction between prM and E proteins, but also suggest the ectodomain of E protein alone could be a potential subunit immunogen without inducing anti-prM response.

  16. LNA effects on DNA binding and conformation

    DEFF Research Database (Denmark)

    Pabon-Martinez, Y Vladimir; Xu, You; Villa, Alessandra

    2017-01-01

    hybridization analysis and electrophoretic mobility shift assay with molecular dynamics (MD) simulations to better understand the underlying structural features of modified ONs in stabilizing duplex- and triplex structures. Particularly, we investigated the role played by the position and number of locked...... nucleic acid (LNA) substitutions in the ON when targeting a c-MYC or FXN (Frataxin) sequence. We found that LNA-containing single strand TFOs are conformationally pre-organized for major groove binding. Reduced content of LNA at consecutive positions at the 3'-end of a TFO destabilizes the triplex...... structure, whereas the presence of Twisted Intercalating Nucleic Acid (TINA) at the 3'-end of the TFO increases the rate and extent of triplex formation. A triplex-specific intercalating benzoquinoquinoxaline (BQQ) compound highly stabilizes LNA-containing triplex structures. Moreover, LNA...

  17. Torsional Arming of Thiomannosyl Donors & Conformational Control of Hexahydropyridazines via pH

    DEFF Research Database (Denmark)

    Olsen, Jacob Ingemar

    be controlled by manipulating the stereochemistry. There are many examples of conformational arming, where an equatorial rich donor is forced towards its more axial rich conformation resulting in a significant increase in reactivity. In order to study this conformational arming further, attempts at synthesizing......H. A relationship between conformation and pKa was established by showing that the pKa directly reflects the conformational equilibrium of conformers. Unfortunately, attaching the hexahydropyridazine to the secondary rim of an α-cyclodextrine was not achieved. Chapter 5 describes the attempted synthesis of seven...... 1). This is due to the higher degree of oxocarbenium ion stabilization exerted by the axial substituents. Therefore, the reactivity of a glycoside donor can be controlled by manipulating the stereochemistry. There are many examples of conformational arming, where an equatorial rich donor is forced...

  18. 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.

  19. Influence of alcoholism history on prognosis of patients with primary hepatocellular carcinoma after R0 resection%酗酒史对原发性肝细胞癌患者R0根治术预后影响的分析

    Institute of Scientific and Technical Information of China (English)

    耿超; 吴力群

    2013-01-01

    OBJECTIVE: To investigate the relationship of alcoholism history and prognosis of the patients with primary hepatocellular carcinoma (HCC) after R0 resection. METHODS: The clinical data of 519 cases of primary HCC underwent R0 resection from January 2001 to December 2009 in Affiliated Hospital of Medical College Qingdao University were analyzed retrospectively. RESULTS: By Kaplan-Meier method, median overall survival (OS) in alcoholism group (n=137) and non-alcoholism group (n = 382) were 42. 0 and 60. 7 months, respectively (Log-rank test:P=0. 024);the median disease-free survival (DFS) was 21. 0 and 31. 0 months (P = 0. 010). Compared with non-alcoholism group,no-anatomical resection,preoperative serum GGT >64 U/L,recurrence during follow-up were much frequently happened in alcoholic patients. Kaplan-Meier( Log-rank text) analysis showed the important factors that influenced OS and DFS as follows :preoperative serum GGT >64 U/L,preoperative serum GGT >64 U/L,liver resection range >2 section,intraoper-atve blood soss ≥1000 mL,intraoperative transfusion,operation cut edge 64 U/mL were OS independent risk factors for OS of HCC patients. No-isolate type,diameter of tumor ≥5 cm,tumor cut edge <0. 5 cm,alcoholism history were independent risk factors for DFS. CONCLUSIONS:The prognosis of HCC patients with alcoholism after R0 resection is poor. History of alcoholismis not the independent risk factors of OS,because the history of alcoholc inflammatory existed,the recurrence rate is higher than that in non-alcoholism.%目的:探讨酗酒史对原发性肝细胞癌(HCC)患者R0切除术后预后的影响.方法:回顾性分析2001-01-01-2009-12-30我院实施的原发性HCC肝切除术519例临床资料,Kaplan-Meier法计算生存率.Cox回归分析影响生存的预后相关因素.结果:519例HCC患者中,酗酒组(137例)和非酗酒组(382例)的患者的中位总体生存时间(OS)分别为42.0和60.7个月(P=0.024),无瘤生存时间(DFS)分别为21.0和31.0

  20. Water drives peptide conformational transitions

    CERN Document Server

    Nerukh, Dmitry

    2011-01-01

    Transitions between metastable conformations of a dipeptide are investigated using classical molecular dynamics simulation with explicit water molecules. The distribution of the surrounding water at different moments before the transitions and the dynamical correlations of water with the peptide's configurational motions indicate that water is the main driving force of the conformational changes.

  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. 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.

  3. 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.

  4. Prolonged signaling at the parathyroid hormone receptor by peptide ligands targeted to a specific receptor conformation.

    Science.gov (United States)

    Okazaki, Makoto; Ferrandon, Sebastien; Vilardaga, Jean-Pierre; Bouxsein, Mary L; Potts, John T; Gardella, Thomas J

    2008-10-28

    The parathyroid hormone receptor (PTHR) is a class B G protein-coupled receptor that plays critical roles in bone and mineral ion metabolism. Ligand binding to the PTHR involves interactions to both the amino-terminal extracellular (N) domain, and transmembrane/extracellular loop, or juxtamembrane (J) regions of the receptor. Recently, we found that PTH(1-34), but not PTH-related protein, PTHrP(1-36), or M-PTH(1-14) (M = Ala/Aib(1),Aib(3),Gln(10),Har(11),Ala(12),Trp(14),Arg(19)), binds to the PTHR in a largely GTPgammaS-resistant fashion, suggesting selective binding to a novel, high-affinity conformation (R(0)), distinct from the GTPgammaS-sensitive conformation (RG). We examined the effects in vitro and in vivo of introducing the M substitutions, which enhance interaction to the J domain, into PTH analogs extended C-terminally to incorporate residues involved in the N domain interaction. As compared with PTH(1-34), M-PTH(1-28) and M-PTH(1-34) bound to R(0) with higher affinity, produced more sustained cAMP responses in cells, formed more stable complexes with the PTHR in FRET and subcellular localization assays, and induced more prolonged calcemic and phosphate responses in mice. Moreover, after 2 weeks of daily injection in mice, M-PTH(1-34) induced larger increases in trabecular bone volume and greater increases in cortical bone turnover, than did PTH(1-34). Thus, the putative R(0) PTHR conformation can form highly stable complexes with certain PTH ligand analogs and thereby mediate surprisingly prolonged signaling responses in bone and/or kidney PTH target cells. Controlling, via ligand analog design, the selectivity with which a PTH ligand binds to R(0), versus RG, may be a strategy for optimizing signaling duration time, and hence therapeutic efficacy, of PTHR agonist ligands.

  5. Hot Conformal Gauge Theories

    DEFF Research Database (Denmark)

    Mojaza, Matin; Pica, Claudio; Sannino, Francesco

    2010-01-01

    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 s.......e. they are independent on the specific matter representation.......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. Imaging of conformational changes

    Energy Technology Data Exchange (ETDEWEB)

    Michl, Josef [Univ. of Colorado, Boulder, CO (United States)

    2016-03-13

    Control of intramolecular conformational change in a small number of molecules or even a single one by an application of an outside electric field defined by potentials on nearby metal or dielectric surfaces has potential applications in both 3-D and 2-D nanotechnology. Specifically, the synthesis, characterization, and understanding of designed solids with controlled built-in internal rotational motion of a dipole promises a new class of materials with intrinsic dielectric, ferroelectric, optical and optoelectronic properties not found in nature. Controlled rotational motion is of great interest due to its expected utility in phenomena as diverse as transport, current flow in molecular junctions, diffusion in microfluidic channels, and rotary motion in molecular machines. A direct time-resolved observation of the dynamics of motion on ps or ns time scale in a single molecule would be highly interesting but is also very difficult and has yet to be accomplished. Much can be learned from an easier but still challenging comparison of directly observed initial and final orientational states of a single molecule, which is the basis of this project. The project also impacts the understanding of surface-enhanced Raman spectroscopy (SERS) and single-molecule spectroscopic detection, as well as the synthesis of solid-state materials with tailored properties from designed precursors.

  7. The Conformal Standard Model

    CERN Document Server

    Latosinski, Adam; Meissner, Krzysztof A; Nicolai, Hermann

    2015-01-01

    We present an extended version of the Conformal Standard Model (characterized by the absence of any new intermediate scales between the electroweak scale and the Planck scale) with an enlarged scalar sector coupling to right-chiral neutrinos in such a way that the scalar potential and the Yukawa couplings involving only right-chiral neutrinos are invariant under a new global symmetry SU(3)$_N$ which is broken explicitly only by the Yukawa interaction coupling right-chiral neutrinos and the electroweak lepton doublets. We point out four main advantages of such an enlargement, namely: (1) the economy of the (non-supersymmetric) Standard Model, and thus its observational success, is preserved; (2) thanks to the enlarged scalar sector the RG improved one-loop effective potential is everywhere positive with a stable global minimum, thereby avoiding the notorious instability of the Standard Model vacuum; (3) the pseudo-Goldstone bosons resulting from spontaneous breaking of the SU(3)$_N$ symmetry are natural Dark M...

  8. Eikonalization of Conformal Blocks

    CERN Document Server

    Fitzpatrick, A Liam; Walters, Matthew T; Wang, Junpu

    2015-01-01

    Classical field configurations such as the Coulomb potential and Schwarzschild solution are built from the $t$-channel exchange of many light degrees of freedom. We study the CFT analog of this phenomenon, which we term the `eikonalization' of conformal blocks. We show that when an operator $T$ appears in the OPE $\\mathcal{O}(x) \\mathcal{O}(0)$, then the large spin $\\ell$ Fock space states $[TT \\cdots T]_{\\ell}$ also appear in this OPE with a computable coefficient. The sum over the exchange of these Fock space states in an $\\langle \\mathcal{O} \\mathcal{O} \\mathcal{O} \\mathcal{O} \\rangle$ correlator build the classical `$T$ field' in the dual AdS description. In some limits the sum of all Fock space exchanges can be represented as the exponential of a single $T$ exchange in the 4-pt correlator of $\\mathcal{O}$. Our results should be useful for systematizing $1/\\ell$ perturbation theory in general CFTs and simplifying the computation of large spin OPE coefficients. As examples we obtain the leading $\\log \\ell$...

  9. Regular Submanifolds in Conformal Space Qnp

    Institute of Scientific and Technical Information of China (English)

    Changxiong NIE; Chuanxi WU

    2012-01-01

    The authors study the regular submanifolds in the conformal space Qnp and introduce the submanifold theory in the conformal space Qnp.The first variation formula of the Willmore volume functional of pseudo-Riemannian submanifolds in the conformal space Qnp is given.Finally,the conformal isotropic submanifolds in the conformal space Qnp are classified.

  10. Conformational states of the full-length glucagon receptor

    Science.gov (United States)

    Yang, Linlin; Yang, Dehua; de Graaf, Chris; Moeller, Arne; West, Graham M.; Dharmarajan, Venkatasubramanian; Wang, Chong; Siu, Fai Y.; Song, Gaojie; Reedtz-Runge, Steffen; Pascal, Bruce D.; Wu, Beili; Potter, Clinton S.; Zhou, Hu; Griffin, Patrick R.; Carragher, Bridget; Yang, Huaiyu; Wang, Ming-Wei; Stevens, Raymond C.; Jiang, Hualiang

    2015-07-01

    Class B G protein-coupled receptors are composed of an extracellular domain (ECD) and a seven-transmembrane (7TM) domain, and their signalling is regulated by peptide hormones. Using a hybrid structural biology approach together with the ECD and 7TM domain crystal structures of the glucagon receptor (GCGR), we examine the relationship between full-length receptor conformation and peptide ligand binding. Molecular dynamics (MD) and disulfide crosslinking studies suggest that apo-GCGR can adopt both an open and closed conformation associated with extensive contacts between the ECD and 7TM domain. The electron microscopy (EM) map of the full-length GCGR shows how a monoclonal antibody stabilizes the ECD and 7TM domain in an elongated conformation. Hydrogen/deuterium exchange (HDX) studies and MD simulations indicate that an open conformation is also stabilized by peptide ligand binding. The combined studies reveal the open/closed states of GCGR and suggest that glucagon binds to GCGR by a conformational selection mechanism.

  11. The discodermolide hairpin structure flows from conformationally stable modular motifs.

    Science.gov (United States)

    Jogalekar, Ashutosh S; Kriel, Frederik H; Shi, Qi; Cornett, Ben; Cicero, Daniel; Snyder, James P

    2010-01-14

    (+)-Discodermolide (DDM), a polyketide macrolide from marine sponge, is a potent microtubule assembly promoter. Reported solid-state, solution, and protein-bound DDM conformations reveal the unusual result that a common hairpin conformational motif exists in all three microenvironments. No other flexible microtubule binding agent exhibits such constancy of conformation. In the present study, we combine force-field conformational searches with NMR deconvolution in different solvents to compare DDM conformers with those observed in other environments. While several conformational families are perceived, the hairpin form dominates. The stability of this motif is dictated primarily by steric factors arising from repeated modular segments in DDM composed of the C(Me)-CHX-C(Me) fragment. Furthermore, docking protocols were utilized to probe the DDM binding mode in beta-tubulin. A previously suggested pose is substantiated (Pose-1), while an alternative (Pose-2) has been identified. SAR analysis for DDM analogues differentiates the two poses and suggests that Pose-2 is better able to accommodate the biodata.

  12. An SIS model for cultural trait transmission with conformity bias.

    Science.gov (United States)

    Walters, Caroline E; Kendal, Jeremy R

    2013-12-01

    Epidemiological models have been applied to human health-related behaviors that are affected by social interaction. Typically these models have not considered conformity bias, that is, the exaggerated propensity to adopt commonly observed behaviors or opinions, or content biases, where the content of the learned trait affects the probability of adoption. Here we consider an interaction of these two effects, presenting an SIS-type model for the spread and persistence of a behavior which is transmitted via social learning. Uptake is controlled by a nonlinear dependence on the proportion of individuals demonstrating the behavior in a population. Three equilibrium solutions are found, their linear stability is analyzed and the results are compared with a model for unbiased social learning. Our analysis focuses on the effects of the strength of conformity bias and the effects of content biases which alter a conformity threshold frequency of the behavior, above which there is an exaggerated propensity for adoption. The strength of the conformity bias is found to qualitatively alter the predictions regarding whether the trait becomes endemic within the population and the proportion of individuals who display the trait when it is endemic. As the conformity strength increases, the number of feasible equilibrium solutions increases from two to three, leading to a situation where the stable equilibrium attained is dependent upon the initial state. Varying the conformity threshold frequency directionally alters the behavior invasion threshold. Finally we discuss the possible application of this model to binge drinking behavior.

  13. Movement of elongation factor G between compact and extended conformations.

    Science.gov (United States)

    Salsi, Enea; Farah, Elie; Netter, Zoe; Dann, Jillian; Ermolenko, Dmitri N

    2015-01-30

    Previous structural studies suggested that ribosomal translocation is accompanied by large interdomain rearrangements of elongation factor G (EF-G). Here, we follow the movement of domain IV of EF-G relative to domain II of EF-G using ensemble and single-molecule Förster resonance energy transfer. Our results indicate that ribosome-free EF-G predominantly adopts a compact conformation that can also, albeit infrequently, transition into a more extended conformation in which domain IV moves away from domain II. By contrast, ribosome-bound EF-G predominantly adopts an extended conformation regardless of whether it is interacting with pretranslocation ribosomes or with posttranslocation ribosomes. Our data suggest that ribosome-bound EF-G may also occasionally sample at least one more compact conformation. GTP hydrolysis catalyzed by EF-G does not affect the relative stability of the observed conformations in ribosome-free and ribosome-bound EF-G. Our data support a model suggesting that, upon binding to a pretranslocation ribosome, EF-G moves from a compact to a more extended conformation. This transition is not coupled to but likely precedes both GTP hydrolysis and mRNA/tRNA translocation.

  14. Conformational dynamics of a ligand-free adenylate kinase.

    Directory of Open Access Journals (Sweden)

    Hyun Deok Song

    Full Text Available Adenylate kinase (AdK is a phosphoryl-transfer enzyme with important physiological functions. Based on a ligand-free open structure and a ligand-bound closed structure solved by crystallography, here we use molecular dynamics simulations to examine the stability and dynamics of AdK conformations in the absence of ligands. We first perform multiple simulations starting from the open or the closed structure, and observe their free evolutions during a simulation time of 100 or 200 nanoseconds. In all seven simulations starting from the open structure, AdK remained stable near the initial conformation. The eight simulations initiated from the closed structure, in contrast, exhibited large variation in the subsequent evolutions, with most (seven undergoing large-scale spontaneous conformational changes and approaching or reaching the open state. To characterize the thermodynamics of the transition, we propose and apply a new sampling method that employs a series of restrained simulations to calculate a one-dimensional free energy along a curved pathway in the high-dimensional conformational space. Our calculated free energy profile features a single minimum at the open conformation, and indicates that the closed state, with a high (∼13 kcal/mol free energy, is not metastable, consistent with the observed behaviors of the unrestrained simulations. Collectively, our simulations suggest that it is energetically unfavorable for the ligand-free AdK to access the closed conformation, and imply that ligand binding may precede the closure of the enzyme.

  15. Energy levels and quantum states of [Leu]enkephalin conformations based on theoretical and experimental investigations

    Energy Technology Data Exchange (ETDEWEB)

    Abdali, Salim; Jensen, Morten O; Bohr, Henrik [Quantum Protein Centre (QUP), Department of Physics, Bldg. 309, Technical University of Denmark, DK-2800 Kgs. Lyngby (Denmark)

    2003-05-14

    This paper describes a theoretical and experimental study of [Leu]enkephalin conformations with respect to the quantum states of the atomic structure of the peptide. Results from vibrational absorption measurements and quantum calculations are used to outline a quantum picture and to assign vibrational modes to the different conformations. The energy landscape of the conformations is reported as a function of a Hamming distance in Ramachandran space. Molecular dynamics simulations reveal a pronounced stability of the so-called single-bend low-energy conformation, which supports the derived quantum picture of this peptide.

  16. Energy levels and quantum states of [Leu]enkephalin conformations based on theoretical and experimental investigations

    DEFF Research Database (Denmark)

    Abdali, Salim; Jensen, Morten Østergaard; Bohr, Henrik

    2003-01-01

    This paper describes a theoretical and experimental study of [Leu]enkephalin conformations with respect to the quantum estates of the atomic structure of the peptide. Results from vibrational absorption measurements and quantum calculations are used to outline a quantum picture and to assign...... vibrational modes to the different conformations. The energy landscape of the conformations is reported as a function of a Hamming distance in Ramachandran space. Molecular dynamics simulations reveal a pronounced stability of the so-called single-bend low-energy conformation, which supports the derived...... quantum picture of this peptide....

  17. Conformal Patterson-Walker metrics

    CERN Document Server

    Hammerl, Matthias; Šilhan, Josef; Taghavi-Chabert, Arman; Žádník, Vojtěch

    2016-01-01

    The classical Patterson-Walker construction of a split-signature (pseudo-)Riemannian structure from a given torsion-free affine connection is generalized to a construction of a split-signature conformal structure from a given projective class of connections. A characterization of the induced structures is obtained. We achieve a complete description of Einstein metrics in the conformal class formed by the Patterson-Walker metric. Finally, we describe all symmetries of the conformal Patterson-Walker metric. In both cases we obtain descriptions in terms of geometric data on the original structure.

  18. Conformational Asymmetry and Quasicrystal Approximants in Linear Diblock Copolymers

    Science.gov (United States)

    Schulze, Morgan W.; Lewis, Ronald M.; Lettow, James H.; Hickey, Robert J.; Gillard, Timothy M.; Hillmyer, Marc A.; Bates, Frank S.

    2017-05-01

    Small angle x-ray scattering experiments on three model low molar mass diblock copolymer systems containing minority polylactide and majority hydrocarbon blocks demonstrate that conformational asymmetry stabilizes the Frank-Kasper σ phase. Differences in block flexibility compete with space filling at constant density inducing the formation of polyhedral shaped particles that assemble into this low symmetry ordered state with local tetrahedral coordination. These results confirm predictions from self-consistent field theory that establish the origins of symmetry breaking in the ordering of block polymer melts subjected to compositional and conformational asymmetry.

  19. A chemical chaperone induces inhomogeneous conformational changes in flexible proteins.

    Science.gov (United States)

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

    2016-07-27

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

  20. Helical conformations of hexapeptides containing N-terminus diproline segments.

    Science.gov (United States)

    Raghothama, Srinivasarao; Aravinda, Subrayashastry; Shamala, Narayanaswamy; Balaram, Padmanabhan

    2010-01-01

    The role of N-terminus diproline segments in facilitating helical folding in short peptides has been investigated in a set of model hexapeptides of the type Piv-Xxx-Yyy-Aib-Leu-Aib-Phe-OMe (Piv, pivaloyl). Nine sequences have been investigated with the following N-terminus dipeptide segments: (D)Pro-Ala (4) and Pro-PsiPro (5, Psi, pseudoproline), Ala-Ala (6), Ala-Pro (7), Pro-Ala (8), Aib-Ala (9), Ala-Aib (10). The analog sequences Piv-Pro-Pro-Ala-Leu-Aib-Phe-OMe (2) and Piv-Pro-Pro-Ala-Aib-Ala-Aib-OMe (3) have also been studied. Solid state conformations have been determined by X-ray crystallography for peptides 4, 6, and 8 and compared with the previously determined crystal structure of peptide 1 (Boc-Pro-Pro-Aib-Leu-Aib-Val-OMe); (Rai et al., JACS 2006, 128, 7916-7928). Peptides 1 and 6 adopt almost identical helical conformations with unfolding of the helix at the N-terminus Pro (1) residue. Peptide 4 reveals the anticipated (D)Pro-Ala type II' beta-turn, followed by a stretch of 3(10)-helix. Peptide 8 adopts a folded conformation stabilized by four successive 4-->1 intramolecular hydrogen bonds. Ala (2) adopts an alpha(L) conformation, resulting in a type II beta-turn conformation followed by a stretch of 3(10)-helix. Conformational properties in solution were probed using solvent perturbation of NH chemical shifts which permit delineation of hydrogen bonded NH groups and nuclear Overhauser effects (NOEs) between backbone protons, which are diagnostic of local residue conformations. The results suggest that, continuous helical conformations are indeed significantly populated for peptides 2 and 3. Comparison of the results for peptides 1 and 2, suggest that there is a significant influence of the residue that follows diproline segments in influencing backbone folding.

  1. (3n+1)值逻辑系统Ro(L)中公式的真度性质%The Properties of Truth Degrees of Formulas in (3n + 1)-Valued Logic System R0(L)

    Institute of Scientific and Technical Information of China (English)

    吴洪博; 周建仁; 张琼

    2011-01-01

    基于计量逻辑学的思想,在(3n+1)值模糊命题逻辑系统R0(L)中引入了公式真度的概念,研究了其主要性质;给出了公式真度的积分表示,并证明了(3n+1)值逻辑系统Ro(L)中的真度MP规则及真度HS规则;利用真度定义了公式间的相似度与伪距离,从而为在(3n+1)值逻辑系统R0(L)中建立近似推理理论提供了一种可能的框架.%Based on the idea of quantitative logic, the definition of the truth degrees of formulas is proposed in (3n + l)-val ued propositional logic system R0L, and its main properties are discussed. The integral representation of the truth degrees of formu las is given, the truth degree modus ponens and truth degree hypothetical syllogism are proved. The concepts of similarity degree and pseudo-metric among formulas are introduced by means of the truth degree. The work of this paper is the base for establishing the framework of approximate reasoning on (3n + l)-valued propositional logic system R0L.

  2. High levels of CD8-positive lymphocytes expressing CD45R0, granzyme B, and Ki-67 in lymph nodes of HIV-infected individuals are not associated with increased mortality

    DEFF Research Database (Denmark)

    Espersen, C; Pakkenberg, B; Harder, Eva

    2001-01-01

    -seropositive patients and seven HIV-negative patients. Eleven of the HIV-positive patients died within 78 months of biopsy time and 10 patients were alive on July 1, 1998. Double immunohistochemical staining procedures were developed to identify CD8(+) cells expressing CD45R0, granzyme B, and Ki-67. A stereological...

  3. 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

  4. 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...

  5. Graphene-based conformal devices.

    Science.gov (United States)

    Park, Yong Ju; Lee, Seoung-Ki; Kim, Min-Seok; Kim, Hyunmin; Ahn, Jong-Hyun

    2014-08-26

    Despite recent progress in bendable and stretchable thin-film transistors using novel designs and materials, the development of conformal devices remains limited by the insufficient flexibility of devices. Here, we demonstrate the fabrication of graphene-based conformal and stretchable devices such as transistor and tactile sensor on a substrate with a convoluted surface by scaling down the device thickness. The 70 nm thick graphene-based conformal devices displayed a much lower bending stiffness than reported previously. The demonstrated devices provided excellent conformal coverage over an uneven animal hide surface without the need for an adhesive. In addition, the ultrathin graphene devices formed on the three-dimensionally curved animal hide exhibited stable electrical characteristics, even under repetitive bending and twisting. The advanced performance and flexibility demonstrated here show promise for the development and adoption of wearable electronics in a wide range of future applications.

  6. 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.

  7. 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.

  8. Conformal anomalies and gravitational waves

    Science.gov (United States)

    Meissner, Krzysztof A.; Nicolai, Hermann

    2017-09-01

    We argue that the presence of conformal anomalies in gravitational theories can lead to observable modifications to Einstein's equations via the induced anomalous effective actions, whose non-localities can overwhelm the smallness of the Planck scale. The fact that no such effects have been seen in recent cosmological or gravitational wave observations therefore imposes strong restrictions on the field content of possible extensions of Einstein's theory: all viable theories should have vanishing conformal anomalies. We then show that a complete cancellation of conformal anomalies in D = 4 for both the C2 invariant and the Euler (Gauss-Bonnet) invariant E4 can only be achieved for N-extended supergravity multiplets with N ⩾ 5, as well as for M theory compactified to four dimensions. Although there remain open questions, in particular concerning the true significance of conformal anomalies in non-conformal theories, as well as their possible gauge dependence for spin s ⩾3/2, these cancellations suggest a hidden conformal structure of unknown type in these theories.

  9. Sampling Realistic Protein Conformations Using Local Structural Bias

    DEFF Research Database (Denmark)

    Hamelryck, Thomas Wim; Kent, John T.; Krogh, A.

    2006-01-01

    are subsequently accepted or rejected using an energy function. Conceptually, this often corresponds to separating local structural bias from the long-range interactions that stabilize the compact, native state. However, sampling protein conformations that are compatible with the local structural bias encoded......The prediction of protein structure from sequence remains a major unsolved problem in biology. The most successful protein structure prediction methods make use of a divide-and-conquer strategy to attack the problem: a conformational sampling method generates plausible candidate structures, which...... in a given protein sequence is a long-standing open problem, especially in continuous space. We describe an elegant and mathematically rigorous method to do this, and show that it readily generates native-like protein conformations simply by enforcing compactness. Our results have far-reaching implications...

  10. 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, E-mail: suzana.quimica.ufg@hotmail.com [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)

  11. CONFORMANCE IMPROVEMENT USING GELS

    Energy Technology Data Exchange (ETDEWEB)

    Randall S. Seright

    2004-09-30

    This report describes work performed during the third and final year of the project, ''Conformance Improvement Using Gels.'' Corefloods revealed throughput dependencies of permeability reduction by polymers and gels that were much more prolonged during oil flow than water flow. This behavior was explained using simple mobility ratio arguments. A model was developed that quantitatively fits the results and predicts ''clean up'' times for oil productivity when production wells are returned to service after application of a polymer or gel treatment. X-ray computed microtomography studies of gels in strongly water-wet Berea sandstone and strongly oil-wet porous polyethylene suggested that oil penetration through gel-filled pores occurs by a gel-dehydration mechanism, rather than gel-ripping or gel-displacement mechanisms. In contrast, analysis of data from the University of Kansas suggests that the gel-ripping or displacement mechanisms are more important in more permeable, strongly water-wet sandpacks. These findings help to explain why aqueous gels can reduce permeability to water more than to oil under different conditions. Since cement is the most commonly used material for water shutoff, we considered when gels are preferred over cements. Our analysis and experimental results indicated that cement cannot be expected to completely fill (top to bottom) a vertical fracture of any width, except near the wellbore. For vertical fractures with apertures less than 4 mm, the cement slurry will simply not penetrate very far into the fracture. For vertical fractures with apertures greater than 4 mm, the slurry may penetrate a substantial distance into the bottom part of the fracture. However, except near the wellbore, the upper part of the fracture will remain open due to gravity segregation. We compared various approaches to plugging fractures using gels, including (1) varying polymer content, (2) varying placement (extrusion) rate

  12. Stability and bifurcation analysis of a vector-bias model of malaria transmission.

    Science.gov (United States)

    Buonomo, Bruno; Vargas-De-León, Cruz

    2013-03-01

    The vector-bias model of malaria transmission, recently proposed by Chamchod and Britton, is considered. Nonlinear stability analysis is performed by means of the Lyapunov theory and the LaSalle Invariance Principle. The classical threshold for the basic reproductive number, R(0), is obtained: if R(0)>1, then the disease will spread and persist within its host population. If R(0)1, the endemic persistence of the disease has been proved to hold also for the extended model. This last result is obtained by means of the geometric approach to global stability. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. To conform or not to conform: spontaneous conformity diminishes the sensitivity to monetary outcomes.

    Science.gov (United States)

    Yu, Rongjun; Sun, Sai

    2013-01-01

    When people have different opinions in a group, they often adjust their own attitudes and behaviors to match the group opinion, known as social conformity. The affiliation account of normative conformity states that people conform to norms in order to 'fit in', whereas the accuracy account of informative conformity posits that the motive to learn from others produces herding. Here, we test another possibility that following the crowd reduces the experienced negative emotion when the group decision turns out to be a bad one. Using event related potential (ERP) combined with a novel group gambling task, we found that participants were more likely to choose the option that was predominately chosen by other players in previous trials, although there was little explicit normative pressure at the decision stage and group choices were not informative. When individuals' choices were different from others, the feedback related negativity (FRN), an ERP component sensitive to losses and errors, was enhanced, suggesting that being independent is aversive. At the outcome stage, the losses minus wins FRN effect was significantly reduced following conformity choices than following independent choices. Analyses of the P300 revealed similar patterns both in the response and outcome period. Our study suggests that social conformity serves as an emotional buffer that protects individuals from experiencing strong negative emotion when the outcomes are bad.

  14. Vibrational spectrum, ab initio calculations, conformational equilibria and torsional modes of 1,3-dichloropropane

    Science.gov (United States)

    Duffy, Daniel J.; Quenneville, Jason; Baumbaugh, T. M.; Kitchener, S. A.; McCormick, R. K.; Dormady, C. N.; Croce, T. A.; Navabi, A.; Stidham, Howard D.; Hsu, Shaw L.; Guirgis, Gamil A.; Deng, Shiping; Durig, James R.

    2004-02-01

    Ab initio calculations are reported for three of four possible conformers of 1,3-dichloropropane. The fourth conformer, with C s symmetry, has a predicted enthalpy difference of more than 1500 cm -1 from the most stable conformer from each calculation regardless of the basis set used, so there is little chance of observing it. Thus, there is no evidence in the infrared or Raman spectrum of the presence of a fourth conformer. The order of stability given by the ab initio calculations is C 2(GG)>C 1(AG)>C 2v(AA)>C s(GG'), where A indicates the anti form for one of the CH 2Cl groups and G indicates the gauche conformation for the other CH 2Cl group relative to the plane of the carbon atoms. Almost every band observed can be confidently assigned to one or another of the conformers. Many observed bands proved to be of a composite nature, with several nearly coincident vibrations of different conformers contributing to the band contour. Nonetheless, a complete assignment of fundamentals is possible for the most stable C 2 conformer, and 5 of the fundamentals of the C 2v conformer and 13 those of the C 1 conformer can be confidently assigned.

  15. 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

  16. Mass Independent Entropy Products in Conformal Gravity

    CERN Document Server

    Pradhan, Parthapratim

    2016-01-01

    In this work we investigate the thermodynamic properties of conformal holography in four dimensions. We compute the \\emph{area(or entropy) functional} relation for this black hole. We consider both dS and AdS cases. Thermodynamic stability is studied by computing the specific heat. The phase transition occurs at a certain condition. Various types of phase structure has been given for various values of $a$ and $\\Lambda$. In the limit $a=0$, one finds the result of Schwarzschild-dS and Schwarzschild-AdS cases. In the limit $aM<<1$, one obtains the result of Grumiler space-time. Where $a$ is defined in the metric and $M$ is the mass parameter.The \\emph{thermodynamic volume functional} relation is derived in the extended phase space. The \\emph{mass-independent} entropy functional relation and thermodynamic volume functional relation that we have derived could turn out to be an \\emph{universal} quantity.

  17. Unveiling the Sweet Conformations of Ketohexoses

    Science.gov (United States)

    Bermudez, C.; Pena, I.; Cabezas, C.; Daly, A. M.; Mata, S.; Alonso, J. L.

    2013-06-01

    The conformational behavior of ketohexoses D-Fructose, L-Sorbose, D-Tagatose and D-Psicose has been revealed from their rotational spectra. A broadband microwave spectrometer (CP-FTMW) has been used to rapidly acquire the rotational spectra in the 6 to 12 GHz frequency range. All observed species are stabilized by complicated intramolecular hydrogen-bonding networks. Structural motifs related to the sweetness of ketohexoses are revealed. G. G. Brown, B. C. Dian, K. O. Douglass, S. M. Geyer, S. T. Shipman, B. H. Pate, Rev. Sci. Instrum. 2008, 79, 053103. S. Mata, I. Peña, C. Cabezas, J. C. López, J. L. Alonso, J. Mol. Spectrosc. 2012, 280, 91.

  18. Entanglement Temperature in Non-conformal Cases

    CERN Document Server

    He, Song; Wu, Jun-Bao

    2013-01-01

    Potential reconstruction can be used to find various analytical asymptotical AdS solutions in Einstein dilation system generally. We have generated two simple solutions without physical singularity called zero temperature solutions. We also proposed a numerical way to obtain black hole solution in Einstein dilaton system with special dilaton potential. By using this method, we obtain the corresponding black hole solutions numerically and investigate the thermal stability of the black hole by comparing the free energy of thermal gas and the corresponding black hole. In two groups of non-conformal gravity solutions obtained in this paper, we find that the two thermal gas solutions are more unstable than black hole solutions respectively. Finally, we consider black hole solutions as a thermal state of zero temperature solutions to check that the first thermal dynamical law exists in entanglement system from holographic point of view.

  19. Conformity Behavior During a Fire Disaster

    National Research Council Canada - National Science Library

    Duo, Qi; Shen, Huizhang; Zhao, Jidi; Gong, Xiaomin

    2016-01-01

    ..., the number of choices offered for making an escape was negatively related to conformity behavior, and decision-making performance was found to be a dual mediator both between the level of fear activation and conformity behavior and between the number of choices and conformity behavior. Keywords: conformity behavior, fire disaster, fear activation, number...

  20. Group Cohesiveness, Deviation, Stress, and Conformity

    Science.gov (United States)

    1993-08-11

    Yuke1son, Weinberg & Jackson , 1984; Carron & Chelladurai, 1981). The classical studies of jury dynamics began to appear within the field of...1987), individuation was negatively correlated with conformity (Santee & Maslach , 1982). Conformity Paradi&ms Host studies of conformity have...appear to affect conformity rates independently of attraction . However, later ~tudies by Dittes and Kelley (1956) and Jackson and Saltzstein (1958

  1. 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...

  2. New potentials for conformal mechanics

    CERN Document Server

    Papadopoulos, G

    2012-01-01

    We show that V=\\alpha x^2+\\beta x^{-2} arises as a potential of 1-dimensional conformal theories. This class of conformal models includes the DFF model \\alpha=0 and the harmonic oscillator \\beta=0. The construction is based on a different embedding of the conformal symmetry group into the time re-parameterizations from that of the DFF model and its generalizations. Depending on the range of the couplings $\\alpha, \\beta$, these models can have a ground state and a well-defined energy spectrum, and exhibit either a $SL(2,\\bR)$ or a SO(3) conformal symmetry. The latter group can also be embedded in Diff(S^1). We also present several generalizations of these models which include the Calogero models with harmonic oscillator couplings and non-linear models with suitable metric and potential couplings. In addition, we give the conditions on the couplings for a class of gaugetheories to admit a SL(2,\\bR) or SO(3) conformal symmetry. We present examples of such systems with general gauge groups and global symmetries t...

  3. Dynamics of particles around time conformal Schwarzschild black hole

    Energy Technology Data Exchange (ETDEWEB)

    Jawad, Abdul; Shahzad, M.U. [COMSATS Institute of Information Technology, Department of Mathematics, Lahore (Pakistan); Ali, Farhad [Kohat University of Science and Technology, Department of Mathematics, Kohat (Pakistan); Abbas, G. [The Islamia University of Bahawalpur, Department of Mathematics, Bahawalpur (Pakistan)

    2016-11-15

    In this work, we present the new technique for discussing the dynamical motion of neutral as well as charged particles in the absence/presence of a magnetic field around the time conformal Schwarzschild black hole. Initially, we find the numerical solutions of geodesics of the Schwarzschild black hole and the time conformal Schwarzschild black hole. We observe that the Schwarzschild spacetime admits the time conformal factor e{sup εf(t)}, where f(t) is an arbitrary function and ε is very small, which causes a perturbation in the spacetimes. This technique also re-scales the energy content of spacetime. We also investigate the thermal stability, horizons and energy conditions corresponding to time conformal Schwarzschild spacetime. Also, we examine the dynamics of a neutral and charged particle around a time conformal Schwarzschild black hole. We investigate the circumstances under which the particle can escape from the vicinity of a black hole after collision with another particle. We analyze the effective potential and effective force of a particle in the presence of a magnetic field with angular momentum graphically. (orig.)

  4. Conformations of terminal sialyloligosaccharide fragments--a molecular dynamics study.

    Science.gov (United States)

    Suresh, M Xavier; Veluraja, K

    2003-06-07

    Molecular dynamics simulations have been performed to understand the conformational features of the terminal sialyloligosaccharide fragments NeuNAc alpha(2-3)Gal, NeuNAc alpha(2-6)Gal, NeuNAc alpha(2-8)NeuNAc and NeuNAc alpha(2-9)NeuNAc. The conformational regions A(i), B(i) and C(i) were identified in the Ramachandran plot. Analysis of the 1000 ps trajectories collected through simulation (2000 ps in the case of NeuNAc alpha (2-9)NeuNAc) revealed that these molecules have conformational propensity in region B(i). The occurrence of these molecules in the common conformational space leads to a structural similarity between them. This structural similarity may be an essential requirement for the neuraminidase activity towards sialyloligosaccharides. The local change in the conformation of the active site residues of neuraminidases may contribute for the specificity differences between different linkages of sialyloligosaccharides. A highly conserved water-mediated hydrogen bond observed in these structures between the sugar residues, acts as an additional stabilizing force.

  5. Logarithmic exotic conformal Galilean algebras

    Energy Technology Data Exchange (ETDEWEB)

    Henkel, Malte, E-mail: Malte.henkel@univ-lorraine.fr [Groupe de Physique Statistique, Institut Jean Lamour (CNRS UMR 7198), Université de Lorraine Nancy, B.P. 70239, F-54506 Vandoeuvre-lès-Nancy Cedex (France); Hosseiny, Ali, E-mail: al_hosseiny@sbu.ac.ir [Department of Physics, Shahid Beheshti University, G.C. Evin, Tehran 19839 (Iran, Islamic Republic of); School of Particles and Accelerators, Institute for Research in Fundamental Sciences (IPM), P.O. Box 19395-5531, Tehran (Iran, Islamic Republic of); Rouhani, Shahin, E-mail: rouhani@ipm.ir [Department of Physics, Sharif University of Technology, P.O. Box 11165-9161, Tehran (Iran, Islamic Republic of); School of Particles and Accelerators, Institute for Research in Fundamental Sciences (IPM), P.O. Box 19395-5531, Tehran (Iran, Islamic Republic of)

    2014-02-15

    Logarithmic representations of the conformal Galilean algebra (CGA) and the Exotic Conformal Galilean algebra (ECGA) are constructed. This can be achieved by non-decomposable representations of the scaling dimensions or the rapidity indices, specific to conformal Galilean algebras. Logarithmic representations of the non-exotic CGA lead to the expected constraints on scaling dimensions and rapidities and also on the logarithmic contributions in the co-variant two-point functions. On the other hand, the ECGA admits several distinct situations which are distinguished by different sets of constraints and distinct scaling forms of the two-point functions. Two distinct realisations for the spatial rotations are identified as well. This is the first concrete example of a reducible, but non-decomposable representation, without logarithmic terms. Such cases had been anticipated before.

  6. Conformal Mapping for Multiple Terminals

    CERN Document Server

    Wang, Weimin; Wang, Qiang; Ren, Hao

    2015-01-01

    Conformal mapping is an important mathematical tool in many physical and engineering fields, especially in electrostatics, fluid mechanics, classical mechanics, and transformation optics. However in the existing textbooks and literatures, it is only adopted to solve the problems which have only two terminals. Two terminals with electric potential differences, pressure difference, optical path difference, etc., can be mapped conformally onto a solvable structure, e.g., a rectangle, where the two terminals are mapped onto two opposite edges of the rectangle. Here we show a conformal mapping method for multiple terminals, which is more common in practical applications. Through accurate analysis of the boundary conditions, additional terminals or boundaries are folded in the inner of the mapped rectangle. Then the solution will not be influenced. The method is described in several typical situations and two application examples are detailed. The first example is an electrostatic actuator with three electrodes. A ...

  7. Conformal Anomalies and Gravitational Waves

    CERN Document Server

    Meissner, Krzysztof A

    2016-01-01

    We argue that the presence of conformal anomalies in gravitational theories can lead to observable modifications to Einstein's equations via the induced anomalous effective actions, whose non-localities can overwhelm the smallness of the Planck scale. The fact that no such effects have been seen in recent cosmological or gravitational wave observations therefore imposes strong restrictions on the field content of possible extensions of Einstein's theory: all viable theories should have vanishing conformal anomalies. We then show that, among presently known theories, a complete cancellation of conformal anomalies in $D=4$ for both the $C^2$ invariant and the Euler (Gauss-Bonnet) invariant $E_4$ can only be achieved for $N$-extended supergravities with $N\\geq 5$, as well as for M theory compactified to four dimensions.

  8. Lectures on Conformal Field Theory

    CERN Document Server

    Qualls, Joshua D

    2015-01-01

    These lectures notes are based on courses given at National Taiwan University, National Chiao-Tung University, and National Tsing Hua University in the spring term of 2015. Although the course was offered primarily for graduate students, these lecture notes have been prepared for a more general audience. They are intended as an introduction to conformal field theories in various dimensions, with applications related to topics of particular interest: topics include the conformal bootstrap program, boundary conformal field theory, and applications related to the AdS/CFT correspondence. We assume the reader to be familiar with quantum mechanics at the graduate level and to have some basic knowledge of quantum field theory. Familiarity with string theory is not a prerequisite for this lectures, although it can only help.

  9. 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.

  10. Characterizing Protein Structure, Dynamics and Conformation in Lyophilized Solids

    OpenAIRE

    Moorthy, Balakrishnan S.; Iyer, Lavanya K.; Topp, Elizabeth M.

    2015-01-01

    The long-term stability of protein therapeutics in the solid-state depends on the preservation of native structure during lyophilization and in the lyophilized powder. Proteins can reversibly or irreversibly unfold upon lyophilization, acquiring conformations susceptible to degradation during storage. Therefore, characterizing proteins in the dried state is crucial for the design of safe and efficacious formulations. This review summarizes the basic principles and applications of the analytic...

  11. Evidence for weak or linear conformity but not for hyper-conformity in an everyday social learning context.

    Science.gov (United States)

    Claidière, Nicolas; Bowler, Mark; Whiten, Andrew

    2012-01-01

    Conformity is thought to be an important force in cultural evolution because it has the potential to stabilize cooperation in large groups, potentiate group selection and thus explain uniquely human behaviors. However, the effects of such conformity on cultural and biological evolution will depend much on the way individuals are influenced by the frequency of alternative behavioral options witnessed. Theoretical modeling has suggested that only what we refer to as 'hyper-conformity', an exaggerated tendency to perform the most frequent behavior witnessed in other individuals, is able to increase within-group homogeneity and between-group diversity, for instance. Empirically however, few experiments have addressed how the frequency of behavior witnessed affects behavior. Accordingly we performed an experiment to test for the presence of conformity in a natural situation with humans. Visitors to a Zoo exhibit were invited to write or draw answers to questions on A5 cards and potentially win a small prize. We manipulated the proportion of existing writings versus drawings visible to visitors and measured the proportion of written cards submitted. We found a strong and significant effect of the proportion of text displayed on the proportion of text in the answers, thus demonstrating social learning. We show that this effect is approximately linear, with potentially a small, weak-conformist component but no hyper-conformist one. The present experiment therefore provides evidence for linear conformity in humans in a very natural context.

  12. Social influence: compliance and conformity.

    Science.gov (United States)

    Cialdini, Robert B; Goldstein, Noah J

    2004-01-01

    This review covers recent developments in the social influence literature, focusing primarily on compliance and conformity research published between 1997 and 2002. The principles and processes underlying a target's susceptibility to outside influences are considered in light of three goals fundamental to rewarding human functioning. Specifically, targets are motivated to form accurate perceptions of reality and react accordingly, to develop and preserve meaningful social relationships, and to maintain a favorable self-concept. Consistent with the current movement in compliance and conformity research, this review emphasizes the ways in which these goals interact with external forces to engender social influence processes that are subtle, indirect, and outside of awareness.

  13. 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

  14. Nonlocal gravity: Conformally flat spacetimes

    CERN Document Server

    Bini, Donato

    2016-01-01

    The field equations of the recent nonlocal generalization of Einstein's theory of gravitation are presented in a form that is reminiscent of general relativity. The implications of the nonlocal field equations are studied in the case of conformally flat spacetimes. Even in this simple case, the field equations are intractable. Therefore, to gain insight into the nature of these equations, we investigate the structure of nonlocal gravity in two-dimensional spacetimes. While any smooth 2D spacetime is conformally flat and satisfies Einstein's field equations, only a subset containing either a Killing vector or a homothetic Killing vector can satisfy the field equations of nonlocal gravity.

  15. Conformational preferences of γ-aminobutyric acid in the gas phase and in water

    Science.gov (United States)

    Song, Il Keun; Kang, Young Kee

    2012-09-01

    The conformational study of γ-aminobutyric acid (GABA) has been carried out at the M06-2X/cc-pVTZ level of theory in the gas phase and the SMD M06-2X/cc-pVTZ level of theory in water. In the gas phase, the folded conformation gG1 with gauche- and gauche+ conformations for the Cβsbnd Cα and Cγsbnd Cβ bonds, respectively, is found to be lowest in energy and enthalpy, which can be ascribed to the favored hyperconjugative n → π* interaction between the lone electron pair of the amine nitrogen atom and the Cdbnd O bond of the carboxylic group and the favored antiparallel dipole-dipole interaction between the Nsbnd H bond and the Cdbnd O bond. In addition, the intramolecular hydrogen bonds between the carboxylic group and the amine Nsbnd H group have contributed to stabilize some low-energy conformers. However, the most preferred conformation is found to be tG1 and more stable by 0.4 kcal/mol in ΔG than the conformer gG1, in which the favored entropic term due to the conformational flexibility and the other favored n → σ*, σ → σ*, and π → σ* interactions seem to play a role. The conformational preferences of the neutral GABA calculated by ΔG's are reasonably consistent with the populations deduced from FT microwave spectroscopy in supersonic jets combined with laser ablation. In water, the two folded conformers Gg and gG of the zwitterionic GABA are dominantly populated, each of which has the population of 47%, and the hydrogen bond between the ammonium Nsbnd H group and the lone electron pair of the Csbnd O- group seems to be crucial in stabilizing these conformers. Our calculated result that the folded conformers preferentially exist in water is consistent with the 1H NMR experiments in D2O.

  16. Conformational preferences of chiral molecules: free-jet rotational spectrum of 1-(4-fluorophenyl)-1-ethanol

    Energy Technology Data Exchange (ETDEWEB)

    Velino, Biagio [Dipartimento di Chimica Fisica e Inorganica dell' Universita, Viale Risorgimento 4, I-40136 Bologna (Italy); Satta, Mauro [Dipartimento di Chimica, Universita di Roma ' La Sapienza' and CNR (IMIP and ISC), Ple Aldo Moro 5, Roma (Italy); Caminati, Walther [Dipartimento di Chimica ' G Ciamician' dell' Universita, Via Selmi 2, I-40126 Bologna (Italy)], E-mail: walther.caminati@unibo.it

    2008-11-15

    The rotational spectra of normal and O-d species of the most stable conformer of chiral 1-(4-fluorophenyl)-1-ethanol have been measured by free-jet absorption millimeter-wave spectroscopy. The observed species is stabilized by an O-H-{pi} interaction and it is at least 1 kcal mol{sup -1} more stable than the remaining conformers.

  17. Molecular mechanics conformational analysis of tylosin

    Science.gov (United States)

    Ivanov, Petko M.

    1998-01-01

    The conformations of the 16-membered macrolide antibiotic tylosin were studied with molecular mechanics (AMBER∗ force field) including modelling of the effect of the solvent on the conformational preferences (GB/SA). A Monte Carlo conformational search procedure was used for finding the most probable low-energy conformations. The present study provides complementary data to recently reported analysis of the conformations of tylosin based on NMR techniques. A search for the low-energy conformations of protynolide, a 16-membered lactone containing the same aglycone as tylosin, was also carried out, and the results were compared with the observed conformation in the crystal as well as with the most probable conformations of the macrocyclic ring of tylosin. The dependence of the results on force field was also studied by utilizing the MM3 force field. Some particular conformations were computed with the semiempirical molecular orbital methods AM1 and PM3.

  18. Youth Conformity Regarding Institutions and Media

    Directory of Open Access Journals (Sweden)

    Nikolay Ivantchev

    2012-10-01

    Full Text Available An experiment on conformity was carried out. The participants were 95 youths. The scale “Conformity – Autonomy” from I. Karagiozov’s questionnaire for locus of control (1998 was also used. The results indicated the prevalence of youth conformity regarding institutions and media. The different types of conformity were related to each other. The subjects’ gender and the experimentators’ gender mediated the connections between the both types of conformity. The female youths conformed more with institutions than the male youths, but there were not any significant gender differences in their conform behavior regarding media (magazines. More male youths conformed for the magazines when the experimentator was a woman. More female youths conformed for the magazines when the experimentator was a man.

  19. Quasilocal rotating conformal Killing horizons

    CERN Document Server

    Chatterjee, Ayan

    2015-01-01

    The formulation of quasi-local conformal Killling horizons(CKH) is extended to include rotation. This necessitates that the horizon be foliated by 2-spheres which may be distorted. Matter degrees of freedom which fall through the horizon is taken to be a real scalar field. We show that these rotating CKHs also admit a first law in differential form.

  20. Conformal mapping for multiple terminals

    Science.gov (United States)

    Wang, Weimin; Ma, Wenying; Wang, Qiang; Ren, Hao

    2016-11-01

    Conformal mapping is an important mathematical tool that can be used to solve various physical and engineering problems in many fields, including electrostatics, fluid mechanics, classical mechanics, and transformation optics. It is an accurate and convenient way to solve problems involving two terminals. However, when faced with problems involving three or more terminals, which are more common in practical applications, existing conformal mapping methods apply assumptions or approximations. A general exact method does not exist for a structure with an arbitrary number of terminals. This study presents a conformal mapping method for multiple terminals. Through an accurate analysis of boundary conditions, additional terminals or boundaries are folded into the inner part of a mapped region. The method is applied to several typical situations, and the calculation process is described for two examples of an electrostatic actuator with three electrodes and of a light beam splitter with three ports. Compared with previously reported results, the solutions for the two examples based on our method are more precise and general. The proposed method is helpful in promoting the application of conformal mapping in analysis of practical problems.

  1. 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...

  2. 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...

  3. Conformal Relativity: Theory and Observations

    CERN Document Server

    Pervushin, V; Zorin, A

    2005-01-01

    Theoretical and observational arguments are listed in favor of a new principle of relativity of units of measurements as the basis of a conformal-invariant unification of General Relativity and Standard Model by replacement of all masses with a scalar (dilaton) field. The relative units mean conformal observables: the coordinate distance, conformal time, running masses, and constant temperature. They reveal to us a motion of a universe along its hypersurface in the field space of events like a motion of a relativistic particle in the Minkowski space, where the postulate of the vacuum as a state with minimal energy leads to arrow of the geometric time. In relative units, the unified theory describes the Cold Universe Scenario, where the role of the conformal dark energy is played by a free minimal coupling scalar field in agreement with the most recent distance-redshift data from type Ia supernovae. In this Scenario, the evolution of the Universe begins with the effect of intensive creation of primordial W-Z-b...

  4. Temperature: Human Regulating, Ants Conforming

    Science.gov (United States)

    Clopton, Joe R.

    2007-01-01

    Biological processes speed up as temperature rises. Procedures for demonstrating this with ants traveling on trails, and data gathered by students on the Argentine ant ("Linepithema humile") are presented. The concepts of temperature regulation and conformity are detailed with a focus on the processes rather than on terms that label the organisms.

  5. A tutorial on conformal prediction

    CERN Document Server

    Shafer, Glenn

    2007-01-01

    Conformal prediction uses past experience to determine precise levels of confidence in new predictions. Given an error probability $\\epsilon$, together with a method that makes a prediction $\\hat{y}$ of a label $y$, it produces a set of labels, typically containing $\\hat{y}$, that also contains $y$ with probability $1-\\epsilon$. Conformal prediction can be applied to any method for producing $\\hat{y}$: a nearest-neighbor method, a support-vector machine, ridge regression, etc. Conformal prediction is designed for an on-line setting in which labels are predicted successively, each one being revealed before the next is predicted. The most novel and valuable feature of conformal prediction is that if the successive examples are sampled independently from the same distribution, then the successive predictions will be right $1-\\epsilon$ of the time, even though they are based on an accumulating dataset rather than on independent datasets. In addition to the model under which successive examples are sampled indepen...

  6. Correct Representation of Conformational Equilibria.

    Science.gov (United States)

    Fulop, F.; And Others

    1983-01-01

    In representing conformational equilibria of compounds having only one chiral center, erroneous formulas showing different antipodes on the two sides of the equilibrium are rare. In contrast, with compounds having two or more chiral centers especially with saturated heterocycles, this erroneous representation occurs frequently in the chemical…

  7. 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 the $...

  8. Temperature: Human Regulating, Ants Conforming

    Science.gov (United States)

    Clopton, Joe R.

    2007-01-01

    Biological processes speed up as temperature rises. Procedures for demonstrating this with ants traveling on trails, and data gathered by students on the Argentine ant ("Linepithema humile") are presented. The concepts of temperature regulation and conformity are detailed with a focus on the processes rather than on terms that label the organisms.

  9. Soil aggregate stability within the morphologically diverse area

    Science.gov (United States)

    Jaksik, Ondrej; Kodesova, Radka; Kubis, Adam; Klement, Ales; Fer, Miroslav

    2013-04-01

    . The highest aggregate stability was measured on soils sampled at relatively flat upper parts, which were only slightly influenced by erosion processes. Higher stability was also obtained on base slope, where the sedimentation of previously eroded soil material occurred. Following correlations were obtained between different test results: R=0.911 for WSA and KV1, R=0.481 for WSA and KV2, R=0.700 for WSA and KV3. The statistical significant correlation was found between WSA index and SOM (R=0.403), WSA and pH_CaCl2 (R=-0.360), WSA and Mnd (R=0.408), WSA and Mno (R=0.355), KV1 and SOM (R=-0.377), KV1 and pH_CaCl2 (R=0.352), KV2 and CO3 (R=0.379), KV3 and pH_CaCl2 (R=0.376). We also found statistical significant correlation between WSA index and two terrain attributes (plan curvature R=-0.490, and total curvature R=-0.501). Acknowledgment: Authors acknowledge the financial support of the Ministry of Agriculture of the Czech Republic (QJ1230319). References Le Bissonnais Y. 1996. Aggregate stability and assessment of soil crustability and erodibility: Theory and methodology. Eur. J. Soil Sci. 47: 425-437. Nimmo J.R., Perkins K.S. 2002. Aggregate stability and size distribution, pp. 317-328. In: Dane J. H. & Topp G.C. (eds), Methods of Soil Analysis, Part 4 - Physical Methods. Soil Science Society of America, Inc. Madison, USA.

  10. The extended Conformal Einstein field equations with matter: the Einstein-Maxwell field

    CERN Document Server

    Lübbe, Christian

    2011-01-01

    A discussion is given of the conformal Einstein field equations coupled with matter whose energy-momentum tensor is trace-free. These resulting equations are expressed in terms of a generic Weyl connection. The article shows how in the presence of matter it is possible to construct a conformal gauge which allows to know \\emph{a priori} the location of the conformal boundary. In vacuum this gauge reduces to the so-called conformal Gaussian gauge. These ideas are applied to obtain: (i) a new proof of the stability of Einstein-Maxwell de Sitter-like spacetimes; (ii) a proof of the semi-global stability of purely radiative Einstein-Maxwell spacetimes.

  11. Fake Conformal Symmetry in Unimodular Gravity

    CERN Document Server

    Oda, Ichiro

    2016-01-01

    We study Weyl symmetry (local conformal symmetry) in unimodular gravity. It is shown that the Noether currents for both Weyl symmetry and global scale symmetry, identically vanish as in the conformally invariant scalar-tensor gravity. We clearly explain why in the class of conformally invariant gravitational theories, the Noether currents vanish by starting with the conformally invariant scalar-tensor gravity. Moreover, we comment on both classical and quantum-mechanical equivalences among Einstein's general relativity, the conformally invariant scalar-tensor gravity and the Weyl-transverse (WTDiff) gravity. Finally, we discuss the Weyl current in the conformally invariant scalar action and see that it is also vanishing.

  12. Fake conformal symmetry in unimodular gravity

    Science.gov (United States)

    Oda, Ichiro

    2016-08-01

    We study Weyl symmetry (local conformal symmetry) in unimodular gravity. It is shown that the Noether currents for both Weyl symmetry and global scale symmetry vanish exactly as in conformally invariant scalar-tensor gravity. We clearly explain why in the class of conformally invariant gravitational theories, the Noether currents vanish by starting with conformally invariant scalar-tensor gravity. Moreover, we comment on both classical and quantum-mechanical equivalences in Einstein's general relativity, conformally invariant scalar-tensor gravity, and the Weyl-transverse gravity. Finally, we discuss the Weyl current in the conformally invariant scalar action and see that it is also vanishing.

  13. Effects of branched polyethylene glycol derivative crosslinking on the structure and conformation stability of bovine tendon type Ⅰ collagen%枝化状聚乙二醇对牛跟腱Ⅰ型胶原结构与构象稳定性的影响

    Institute of Scientific and Technical Information of China (English)

    邹明晖; 周建良; 陈义初; 周诚; 史嘉玮; 董念国

    2011-01-01

    Objective The triple helix of collagen is the basis of its biological function, such as cell adhesion and tissue remodeling. Crosslinking of collagen with chemical agent will improve the biomechanical properties. However, the effects of differernt crosslinking agents on the structure and conformation stability of type Ⅰ collagen are rarely investigated. Methods The branched polyethylene glycol ( PEG)derivative ( MW 12 kD) was used as crosslinking agent, and allowed to react with bovine achilles' s tendon type Ⅰ collagen modified by succinimidylacetylthioacetate (SATA). The ability of resistance of crosslinked collagen to enzymatic degradation was investigated by measuring the release of hydroxyproline, and differential scanning calorimeter ( DSC ) was taken to determine the thermal denaturation temperature. The effect of PEG on the riple helix of collagen was studied by circular dichroism ( CD) . Results The resistance ability of PEG crosslinked collagen was strongly enhanced when compared with that of control group ( P <0. 05 ) , and the thermal denaturation temperature was also significantly rised. CD demonstrated that PEG crosslinking did not result in the destruction of the triple helix conformation of type Ⅰ collagen. Conclusion Branched PEG derivative used in this study is a promising polymer crosslinking agent that may be utilized in the modification of type Ⅰ collagen.%目的 观察枝化状聚乙二醇对牛跟腱Ⅰ型胶原结构与构象稳定性的影响.方法 以牛跟腱Ⅰ型胶原为原料,以枝化状聚乙二醇为交联剂,在有效交联的前提下,通过测定羟脯氨酸含量观察聚乙二醇交联对胶原酶解稳定性的影响,采用示差扫描量热法(DSC)观察胶原热变性温度,采用圆二色光谱法(CD)观察聚乙二醇对胶原三螺旋构象稳定性的影响.结果 枝化状聚乙二醇交联组24 h降解率为26.79%,而对照组则达97.39%,两者比较差异有统计学意义(P<0.05).

  14. SAMPL5: 3D-RISM partition coefficient calculations with partial molar volume corrections and solute conformational sampling

    Science.gov (United States)

    Luchko, Tyler; Blinov, Nikolay; Limon, Garrett C.; Joyce, Kevin P.; Kovalenko, Andriy

    2016-11-01

    Implicit solvent methods for classical molecular modeling are frequently used to provide fast, physics-based hydration free energies of macromolecules. Less commonly considered is the transferability of these methods to other solvents. The Statistical Assessment of Modeling of Proteins and Ligands 5 (SAMPL5) distribution coefficient dataset and the accompanying explicit solvent partition coefficient reference calculations provide a direct test of solvent model transferability. Here we use the 3D reference interaction site model (3D-RISM) statistical-mechanical solvation theory, with a well tested water model and a new united atom cyclohexane model, to calculate partition coefficients for the SAMPL5 dataset. The cyclohexane model performed well in training and testing (R=0.98 for amino acid neutral side chain analogues) but only if a parameterized solvation free energy correction was used. In contrast, the same protocol, using single solute conformations, performed poorly on the SAMPL5 dataset, obtaining R=0.73 compared to the reference partition coefficients, likely due to the much larger solute sizes. Including solute conformational sampling through molecular dynamics coupled with 3D-RISM (MD/3D-RISM) improved agreement with the reference calculation to R=0.93. Since our initial calculations only considered partition coefficients and not distribution coefficients, solute sampling provided little benefit comparing against experiment, where ionized and tautomer states are more important. Applying a simple pK_{ {a}} correction improved agreement with experiment from R=0.54 to R=0.66, despite a small number of outliers. Better agreement is possible by accounting for tautomers and improving the ionization correction.

  15. Effects of lipid environment on the conformational changes of an ABC importer.

    Science.gov (United States)

    Rice, Austin J; Alvarez, Frances J D; Davidson, Amy L; Pinkett, Heather W

    2014-01-01

    In order to shuttle substrates across the lipid bilayer, membrane proteins undergo a series of conformation changes that are influenced by protein structure, ligands, and the lipid environment. To test the effect of lipid on conformation change of the ABC transporter MolBC, EPR studies were conducted in lipids and detergents of variable composition. In both a detergent and lipid environment, MolBC underwent the same general conformation changes as detected by site-directed EPR spectroscopy. However, differences in activity and the details of the EPR analysis indicate conformational rigidity that is dependent on the lipid environment. From these observations, we conclude that native-like lipid mixtures provide the transporter with greater activity and conformational flexibility as well as technical advantages such as reconstitution efficiency and protein stability.

  16. Conformational equilibrium of phenylacetic acid and its halogenated analogues through theoretical studies, NMR and IR spectroscopy

    Science.gov (United States)

    Levandowski, Mariana N.; Rozada, Thiago C.; Melo, Ulisses Z.; Basso, Ernani A.; Fiorin, Barbara C.

    2017-03-01

    This paper presents a study on the conformational preferences of phenylacetic acid (PA) and its halogenated analogues (FPA, CPA, BPA). To clarify the effects that rule these molecules' behaviour, theoretical calculations were used, for both the isolated phase and solution, combined with nuclear magnetic resonance (NMR) and infrared (IR) spectroscopy. Most conformations of phenylacetic acid and its halogenated derivatives are stabilized through the hyperconjugative effect, which rules the conformational preference. NMR analyses showed that even with the variation in medium polarity, there was no significant change in the conformation population. Infrared spectroscopy showed similar results for all compounds under study. In most spectra, two bands were found through the carbonyl deconvolution, which is in accordance with the theoretical data. It was possible to prove that variation in the nature of the substituent in the ortho position had no significant influence on the conformational equilibrium.

  17. Conformational Structure of Tyrosine, Tyrosyl-Glycine, and Tyrosyl-Glycyl-Glycine by Double Resonance Spectroscopy

    Science.gov (United States)

    Abo-Riziq, Ali; Grace, Louis; Crews, Bridgit; Callahan, Michael P,; van Mourik, Tanja; de Vries, Mattanjah S,

    2011-01-01

    We investigated the variation in conformation for the amino acid tyrosine (Y), alone and in the small peptides tyrosine-glycine (YC) and tyrosine-glycine-glycine (YGG), in the gas phase by using UV-UV and IR-UV double resonance spectroscopy and density functional theory calculations. For tyrosine we found seven different conformations, for YG we found four different conformations, and for YGG we found three different conformations. As the peptides get larger, we observe fewer stable conformers, despite the increasing complexity and number of degrees of freedom. We find structural trends similar to those in phenylalanine-glycine glycine (FGG) and tryptophan-glycine-glycine (WGG)j however) the effect of dispersive forces in FGG for stabilizing a folded structure is replaced by that of hydrogen bonding in YGG.

  18. An Organic Receptor Isolated in an Unusual Intermediate Conformation: Computation, Crystallography, and Hirshfeld Surface Analysis.

    Science.gov (United States)

    Naik, Indravath Krishna; Sarkar, Rudraditya; Madhu, Vedichi; Bolligarla, Ramababu; Kishore, Ravada; Das, Samar K

    2017-05-04

    1,1″-1,4-Phenylene-bis(methylene)bis-4,4'-bipyridinium cation [C28H24N4](2+) (c), an organic receptor that generally crystallizes in its anti conformation, has recently been shown to be isolated in its syn conformation in an ion-paired compound [C28H24N4][Zn(dmit)2]·2DMF (dmit(2-) = 1,3-dithiole-2-thione-4,5-dithiolate; DMF = dimethylformamide). In this article, we demonstrated that the same receptor [C28H24N4](2+) (c) can also be stabilized in an unusual intermediate conformation (neither syn nor anti) with PF6(-) anion in compound [C28H24N4](PF6)2·(1,4-dioxane) (1·(1,4-dioxane)). The energetically favored anti conformation has been described in its nitrate salt [C28H24N4](NO3)2·2H2O (2·2H2O). Compounds 1·(1,4-dioxane) and 2·2H2O, crystallizing in triclinic and monoclinic systems with space groups P1̅ and P21/n, respectively, were additionally characterized by Hirshfeld surface analysis. The density functional theory calculations are performed to understand the internal mechanism of the stability of various conformers of cationic receptor c, compound 1, and compound 2. In conjunction with the electronic stability of the conformers, the natural bond orbital analysis and conformational equilibrium constants at different temperatures are also calculated to find out the sources of the different stability of the various conformers of experimentally synthesized compounds.

  19. Differential steric effects in Cl reactions with aligned CHD3(v1 = 1) by the R(0) and Q(1) transitions. I. Attacking the excited C-H bond

    Science.gov (United States)

    Wang, Fengyan; Liu, Kopin

    2016-10-01

    When a CHD3 molecule is pumped to the C-H stretching-excited state by absorbing a linearly polarized infrared (IR) photon via the R(0) branch of the v1 = 1←0 transition, the rotational angular momentum j of the prepared state |" separators=" jK > = |" separators=" 10 > preferentially lies in a plane perpendicular to the IR polarization axis ɛIR. By way of contrast, when the Q(1) branch is used, the state of |" separators=" jK > = |" separators=" 1 ± 1 > is prepared with j aligned along the direction of ɛIR. Reported here is a detailed study of the title reaction by actively controlling the collision geometries under these two IR-excitation schemes at collision energy Ec = 8.6 kcal mol-1, using a crossed molecular beam, product imaging approach. We found that under the R(0) excitation, the polarization-dependent differential cross sections for the HCl(v = 0) + CD3(00) channel can largely be understood by invoking dual reaction mechanisms. The forward-scattered products are most likely mediated by a time-delayed resonance mechanism—as the formation of the HCl(v = 1) + CD3(00) channel, whereas the backward/sideways scattered products are governed by a direct abstraction mechanism. Compared to the previous results at lower Ec of 3.8 kcal mol-1, the sighting of opening-up the attack angle at the transition state of the direct pathway is proposed. Results under the Q(1) excitation are, however, perplexing and bear no obvious correlation to the corresponding ones for the R(0) excitation, defying simple intuitive interpretation. Possible reasons are put forward, which call for theoretical investigations for deeper insights. The results on the alternative isotope channel, DCl + CHD2, will be reported in the following paper.

  20. Protein stability: a crystallographer’s perspective

    Energy Technology Data Exchange (ETDEWEB)

    Deller, Marc C., E-mail: mdeller@stanford.edu [Stanford University, Shriram Center, 443 Via Ortega, Room 097, MC5082, Stanford, CA 94305-4125 (United States); Kong, Leopold [National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), Building 8, Room 1A03, 8 Center Drive, Bethesda, MD 20814 (United States); Rupp, Bernhard [k.-k. Hofkristallamt, 91 Audrey Place, Vista, CA 92084 (United States); Medical University of Innsbruck, Schöpfstrasse 41, A-6020 Innsbruck (Austria)

    2016-01-26

    An understanding of protein stability is essential for optimizing the expression, purification and crystallization of proteins. In this review, discussion will focus on factors affecting protein stability on a somewhat practical level, particularly from the view of a protein crystallographer. Protein stability is a topic of major interest for the biotechnology, pharmaceutical and food industries, in addition to being a daily consideration for academic researchers studying proteins. An understanding of protein stability is essential for optimizing the expression, purification, formulation, storage and structural studies of proteins. In this review, discussion will focus on factors affecting protein stability, on a somewhat practical level, particularly from the view of a protein crystallographer. The differences between protein conformational stability and protein compositional stability will be discussed, along with a brief introduction to key methods useful for analyzing protein stability. Finally, tactics for addressing protein-stability issues during protein expression, purification and crystallization will be discussed.

  1. Thioflavin T templates amyloid β(1-40) conformation and aggregation pathway

    DEFF Research Database (Denmark)

    Di Carlo, Maria Giovanna; Minicozzi, Velia; Foderà, Vito;

    2015-01-01

    in turn rests on the reliability of the probe/labels involved. Here we present evidences of the effect of Thioflavin T (ThT), a worldwide used fluorescent dye to monitor amyloid growth, on the Aβ(1-40) conformation, stability and aggregation. By combining experimental information and Molecular Dynamics...... simulation results, we show that the presence of ThT in solution affects peptide conformation inducing peculiar supramolecular association. In particular ThT interactions with specific Aβ(1-40) residues promote a rigid partially-folded conformation which shifts the balance between different species...

  2. Conformal Window and Correlation Functions in Lattice Conformal QCD

    Science.gov (United States)

    Iwasaki, Y.

    We discuss various aspects of Conformal Field Theories on the Lattice. We mainly investigate the SU(3) gauge theory with Nf degenerate fermions in the fundamental representation, employing the one-plaquette gauge action and the Wilson fermion action. First we make a brief review of our previous works on the phase structure of lattice gauge theories in terms of the gauge coupling constant and the quark mass. We thereby clarify the reason why we conjecture that the conformal window is 7 ≤ Nf ≤ 16. Secondly, we introduce a new concept, "conformal theories with IR cutof" and point out that any numerical simulation on a lattice is bounded by an IR cutoff ∧IR. Then we make predictions that when Nf is within the conformal window, the propagator of a meson G(t) behaves at large t, as G(t) = c exp (-mHt)/tα, that is, a modified Yukawa-type decay form, instead of the usual exponential decay form exp (-mHt), in the small quark mass region. This holds on an any lattice for any coupling constant g, as far as g is between 0 and g*, where g* is the IR fixed point. We verify that numerical results really satisfy the predictions for the Nf = 7 case and the Nf = 16 case. Thirdly, we discuss small number of flavors (Nf = 2 ˜ 6) QCD at finite temperatures. We point out theoretically and verify numerically that the correlation functions at T/Tc > 1 exhibit the characteristics of the conformal function with IR cutoff, an exponential decay with power correction. Investigating our numerical data by a new method which we call the "local-analysis" of propagators, we observe that the Nf = 7 case and the Nf = 2 at T ˜ 2Tc case are similar to each other, while the Nf = 16 case and the Nf = 2 at T = 102 ˜ 105Tc cases are similar to each other. Further, we observe our data are consistent with the picture that the Nf = 7 case and the Nf = 2 at T ˜ 2Tc case are close to the meson unparticle model. On the other hand, the Nf = 16 case and the Nf = 2 at T = 102 ˜ 105Tc cases are close to

  3. Boundary terms of conformal anomaly

    Directory of Open Access Journals (Sweden)

    Sergey N. Solodukhin

    2016-01-01

    Full Text Available We analyze the structure of the boundary terms in the conformal anomaly integrated over a manifold with boundaries. We suggest that the anomalies of type B, polynomial in the Weyl tensor, are accompanied with the respective boundary terms of the Gibbons–Hawking type. Their form is dictated by the requirement that they produce a variation which compensates the normal derivatives of the metric variation on the boundary in order to have a well-defined variational procedure. This suggestion agrees with recent findings in four dimensions for free fields of various spins. We generalize this consideration to six dimensions and derive explicitly the respective boundary terms. We point out that the integrated conformal anomaly in odd dimensions is non-vanishing due to the boundary terms. These terms are specified in three and five dimensions.

  4. Conformal Bootstrap in Mellin Space

    CERN Document Server

    Gopakumar, Rajesh; Sen, Kallol; Sinha, Aninda

    2016-01-01

    We propose a new approach towards analytically solving for the dynamical content of Conformal Field Theories (CFTs) using the bootstrap philosophy. This combines the original bootstrap idea of Polyakov with the modern technology of the Mellin representation of CFT amplitudes. We employ exchange Witten diagrams with built in crossing symmetry as our basic building blocks rather than the conventional conformal blocks in a particular channel. Demanding consistency with the operator product expansion (OPE) implies an infinite set of constraints on operator dimensions and OPE coefficients. We illustrate the power of this method in the epsilon expansion of the Wilson-Fisher fixed point by computing operator dimensions and, strikingly, OPE coefficients to higher orders in epsilon than currently available using other analytic techniques (including Feynman diagram calculations). Our results enable us to get a somewhat better agreement of certain observables in the 3d Ising model, with the precise numerical values that...

  5. 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.

  6. Boundary terms of conformal anomaly

    Energy Technology Data Exchange (ETDEWEB)

    Solodukhin, Sergey N., E-mail: Sergey.Solodukhin@lmpt.univ-tours.fr

    2016-01-10

    We analyze the structure of the boundary terms in the conformal anomaly integrated over a manifold with boundaries. We suggest that the anomalies of type B, polynomial in the Weyl tensor, are accompanied with the respective boundary terms of the Gibbons–Hawking type. Their form is dictated by the requirement that they produce a variation which compensates the normal derivatives of the metric variation on the boundary in order to have a well-defined variational procedure. This suggestion agrees with recent findings in four dimensions for free fields of various spins. We generalize this consideration to six dimensions and derive explicitly the respective boundary terms. We point out that the integrated conformal anomaly in odd dimensions is non-vanishing due to the boundary terms. These terms are specified in three and five dimensions.

  7. Gel dosimetry for conformal radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Gambarini, G. [Department of Physics of the University and INFN, Milan (Italy)]. e-mail: grazia.gambarini@mi.infn.it

    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)

  8. 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.

  9. Conformal Bootstrap in Mellin Space

    Science.gov (United States)

    Gopakumar, Rajesh; Kaviraj, Apratim; Sen, Kallol; Sinha, Aninda

    2017-02-01

    We propose a new approach towards analytically solving for the dynamical content of conformal field theories (CFTs) using the bootstrap philosophy. This combines the original bootstrap idea of Polyakov with the modern technology of the Mellin representation of CFT amplitudes. We employ exchange Witten diagrams with built-in crossing symmetry as our basic building blocks rather than the conventional conformal blocks in a particular channel. Demanding consistency with the operator product expansion (OPE) implies an infinite set of constraints on operator dimensions and OPE coefficients. We illustrate the power of this method in the ɛ expansion of the Wilson-Fisher fixed point by reproducing anomalous dimensions and, strikingly, obtaining OPE coefficients to higher orders in ɛ than currently available using other analytic techniques (including Feynman diagram calculations). Our results enable us to get a somewhat better agreement between certain observables in the 3D Ising model and the precise numerical values that have been recently obtained.

  10. Conformal gravity and "gravitational bubbles"

    CERN Document Server

    Berezin, V A; Eroshenko, Yu N

    2015-01-01

    We describe the general structure of the spherically symmetric solutions in the Weyl conformal gravity. The corresponding Bach equations are derived for the special type of metrics, which can be considered as the representative of the general class. The complete set of the pure vacuum solutions, consisting of two classes, is found. The first one contains the solutions with constant two-dimensional curvature scalar, and the representatives are the famous Robertson--Walker metrics. We called one of them the "gravitational bubbles", which is compact and with zero Weyl tensor. These "gravitational bubbles" are the pure vacuum curved space-times (without any material sources, including the cosmological constant), which are absolutely impossible in General Relativity. This phenomenon makes it easier to create the universe from "nothing". The second class consists of the solutions with varying curvature scalar. We found its representative as the one-parameter family, which can be conformally covered by the thee-para...

  11. Skin-sparing Helical Tomotherapy vs 3D-conformal Radiotherapy for Adjuvant Breast Radiotherapy: In Vivo Skin Dosimetry Study

    Energy Technology Data Exchange (ETDEWEB)

    Capelle, Lisa [Division of Radiation Oncology, Cross Cancer Institute and University of Alberta, Edmonton, Alberta (Canada); Warkentin, Heather; MacKenzie, Marc [Division of Medical Physics, Cross Cancer Institute and University of Alberta, Edmonton, Alberta (Canada); Joseph, Kurian; Gabos, Zsolt; Pervez, Nadeem; Tankel, Keith; Chafe, Susan [Division of Radiation Oncology, Cross Cancer Institute and University of Alberta, Edmonton, Alberta (Canada); Amanie, John [Division of Statistics and Epidemiology, Cross Cancer Institute and University of Alberta, Edmonton, Alberta (Canada); Ghosh, Sunita; Parliament, Matthew [Division of Radiation Oncology, Cross Cancer Institute and University of Alberta, Edmonton, Alberta (Canada); Abdulkarim, Bassam, E-mail: bassam.abdulkarim@mcgill.ca [Division of Radiation Oncology, Cross Cancer Institute and University of Alberta, Edmonton, Alberta (Canada)

    2012-08-01

    Purpose: We investigated whether treatment-planning system (TPS)-calculated dose accurately reflects skin dose received for patients receiving adjuvant breast radiotherapy (RT) with standard three-dimensional conformal RT (3D-CRT) or skin-sparing helical tomotherapy (HT). Methods and Materials: Fifty patients enrolled in a randomized controlled trial investigating acute skin toxicity from adjuvant breast RT with 3D-CRT compared to skin-sparing HT, where a 5-mm strip of ipsilateral breast skin was spared. Thermoluminescent dosimetry or optically stimulated luminescence measurements were made in multiple locations and were compared to TPS-calculated doses. Skin dosimetric parameters and acute skin toxicity were recorded in these patients. Results: With HT there was a significant correlation between calculated and measured dose in the medial and lateral ipsilateral breast (r = 0.67, P<.001; r = 0.44, P=.03, respectively) and the medial and central contralateral breast (r = 0.73, P<.001; r = 0.88, P<.001, respectively). With 3D-CRT there was a significant correlation in the medial and lateral ipsilateral breast (r = 0.45, P=.03; r = 0.68, P<.001, respectively); the medial and central contralateral breast (r = 0.62, P=.001; r = 0.86, P<.001, respectively); and the mid neck (r = 0.42, P=.04, respectively). On average, HT-calculated dose overestimated the measured dose by 14%; 3D-CRT underestimated the dose by 0.4%. There was a borderline association between highest measured skin dose and moist desquamation (P=.05). Skin-sparing HT had greater skin homogeneity (homogeneity index of 1.39 vs 1.65, respectively; P=.005) than 3D-CRT plans. HT plans had a lower skin{sub V50} (1.4% vs 5.9%, respectively; P=.001) but higher skin{sub V40} and skin{sub V30} (71.7% vs 64.0%, P=.02; and 99.0% vs 93.8%, P=.001, respectively) than 3D-CRT plans. Conclusion: The 3D-CRT TPS more accurately reflected skin dose than the HT TPS, which tended to overestimate dose received by 14% in patients

  12. Octonionic geometry and conformal transformations

    CERN Document Server

    Gogberashvili, Merab

    2016-01-01

    We describe space-time using split octonions over the reals and use their group of automorphisms, the non-compact form of Cartan's exceptional Lie group G2, as the main geometrical group of the model. It is studied connections of the G2-rotations of octonionic 8D space with the conformal transformations in 4D Minkowski space-time. It is shown that the dimensional constant needed in these analysis naturally gives the observed value of the cosmological constant.

  13. 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...... the $\\delta$-expansion, for a wide range of number of flavours. We also find that this is always smaller than the anomalous dimension of the fermion mass operator. These findings challenge the partial compositeness paradigm....

  14. 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.

  15. Monogenic Functions in Conformal Geometry

    Directory of Open Access Journals (Sweden)

    Michael Eastwood

    2007-08-01

    Full Text Available Monogenic functions are basic to Clifford analysis. On Euclidean space they are defined as smooth functions with values in the corresponding Clifford algebra satisfying a certain system of first order differential equations, usually referred to as the Dirac equation. There are two equally natural extensions of these equations to a Riemannian spin manifold only one of which is conformally invariant. We present a straightforward exposition.

  16. Conformal theory of galactic halos

    CERN Document Server

    Nesbet, R K

    2011-01-01

    Current cosmological theory describes an isolated galaxy as an observable central galaxy, surrounded by a large spherical halo attributed to dark matter. Galaxy formation by condensation of mass-energy out of a primordial uniform background is shown here to leave a scar, observed as a centripetal gravitational field halo in anomalous galactic rotation and in gravitational lensing. Conformal theory accounts for the otherwise counterintuitive centripetal effect.

  17. All N=4 Conformal Supergravities

    CERN Document Server

    Butter, Daniel; de Wit, Bernard; Sahoo, Bindusar

    2016-01-01

    All N=4 conformal supergravities in four space-time dimensions are constructed. These are the only N=4 supergravity theories whose actions are invariant under off-shell supersymmetry. They are encoded in terms of a holomorphic function that is homogeneous of zeroth degree in scalar fields that parametrize an SU(1,1)/U(1) coset space. When this function equals a constant the Lagrangian is invariant under continuous SU(1,1) transformations.

  18. Anomalous Dimensions of Conformal Baryons

    CERN Document Server

    Pica, Claudio

    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 for a wide range of number of flavours. We also find that this is always smaller than the anomalous dimension of the fermion mass operator. These findings challenge the partial compositeness paradigm.

  19. Exceptional and Spinorial Conformal Windows

    CERN Document Server

    Mojaza, Matin; Ryttov, Thomas A; Sannino, Francesco

    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 to a spinorial representation. We investigate the phase diagram using a purely perturbative four loop analysis, the all-orders beta function and the ladder approximation.

  20. Simple Space-Time Symmetries: Generalizing Conformal Field Theory

    CERN Document Server

    Mack, G; Mack, Gerhard; Riese, Mathias de

    2004-01-01

    We study simple space-time symmetry groups G which act on a space-time manifold M=G/H which admits a G-invariant global causal structure. We classify pairs (G,M) which share the following additional properties of conformal field theory: 1) The stability subgroup H of a point in M is the identity component of a parabolic subgroup of G, implying factorization H=MAN, where M generalizes Lorentz transformations, A dilatations, and N special conformal transformations. 2) special conformal transformations in N act trivially on tangent vectors to the space-time manifold M. The allowed simple Lie groups G are the universal coverings of SU(m,m), SO(2,D), Sp(l,R), SO*(4n) and E_7(-25) and H are particular maximal parabolic subgroups. All these groups G admit positive energy representations. It will also be shown that the classical conformal groups SO(2,D) are the only allowed groups which possess a time reflection automorphism; in all other cases space-time has an intrinsic chiral structure.

  1. A conformal block Farey tail

    Science.gov (United States)

    Maloney, Alexander; Maxfield, Henry; Ng, Gim Seng

    2017-06-01

    We investigate the constraints of crossing symmetry on CFT correlation functions. Four point conformal blocks are naturally viewed as functions on the upper-half plane, on which crossing symmetry acts by PSL(2, Z ) modular transformations. This allows us to construct a unique, crossing symmetric function out of a given conformal block by averaging over PSL(2, Z ). In some two dimensional CFTs the correlation functions are precisely equal to the modular average of the contributions of a finite number of light states. For example, in the two dimensional Ising and tri-critical Ising model CFTs, the correlation functions of identical operators are equal to the PSL(2, Z ) average of the Virasoro vacuum block; this determines the 3 point function coefficients uniquely in terms of the central charge. The sum over PSL(2, Z ) in CFT2 has a natural AdS3 interpretation as a sum over semi-classical saddle points, which describe particles propagating along rational tangles in the bulk. We demonstrate this explicitly for the correlation function of certain heavy operators, where we compute holographically the semi-classical conformal block with a heavy internal operator.

  2. Conformal window and Landau singularities

    CERN Document Server

    Grunberg, G

    2001-01-01

    A physical characterization of Landau singularities is emphasized, which should trace the lower boundary N_f^* of the conformal window in QCD and supersymmetric QCD. A natural way to disentangle ``perturbative'' from ``non-perturbative'' contributions below N_f^* is suggested. Assuming an infrared fixed point is present in the perturbative part of the QCD coupling even in some range below N_f^* leads to the condition gamma(N_f^*)=1, where gamma is the critical exponent. Using the Banks-Zaks expansion, one gets 4conformal window. Some evidence for such a fixed point in QCD is provided through a modified Banks-Zaks expansion. Conformal window amplitudes, which contain power contributions, are show...

  3. Electrophysiological precursors of social conformity.

    Science.gov (United States)

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

    2013-10-01

    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.

  4. 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.

  5. MIXED SELF-CONFORMAL MULTIFRACTAL MEASURES

    Institute of Scientific and Technical Information of China (English)

    Meifeng Dai

    2009-01-01

    Mixed multifractal analysis studies the simultaneous scaling behavior of finitely many measures. A self-conformal measure is a measure invariant under a set of conformal mappings. In this paper, we provide a description of the mixed multifractal theory of finitely many self-conformal measures.

  6. 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...

  7. 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...

  8. 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...

  9. On the cohomology of Leibniz conformal algebras

    Science.gov (United States)

    Zhang, Jiao

    2015-04-01

    We construct a new cohomology complex of Leibniz conformal algebras with coefficients in a representation instead of a module. The low-dimensional cohomology groups of this complex are computed. Meanwhile, we construct a Leibniz algebra from a Leibniz conformal algebra and prove that the category of Leibniz conformal algebras is equivalent to the category of equivalence classes of formal distribution Leibniz algebras.

  10. Recent Advances in Computational Conformal Geometry

    OpenAIRE

    Gu, Xianfeng David; Luo, Feng; Yau, Shing-Tung

    2009-01-01

    Computational conformal geometry focuses on developing the computational methodologies on discrete surfaces to discover conformal geometric invariants. In this work, we briefly summarize the recent developments for methods and related applications in computational conformal geometry. There are two major approaches, holomorphic differentials and curvature flow. Holomorphic differential method is a linear method, which is more efficient and robust to triangulations with lower qua...

  11. Transglutaminase 2 undergoes a large conformational change upon activation.

    Directory of Open Access Journals (Sweden)

    Daniel M Pinkas

    2007-12-01

    Full Text Available Human transglutaminase 2 (TG2, a member of a large family of enzymes that catalyze protein crosslinking, plays an important role in the extracellular matrix biology of many tissues and is implicated in the gluten-induced pathogenesis of celiac sprue. Although vertebrate transglutaminases have been studied extensively, thus far all structurally characterized members of this family have been crystallized in conformations with inaccessible active sites. We have trapped human TG2 in complex with an inhibitor that mimics inflammatory gluten peptide substrates and have solved, at 2-A resolution, its x-ray crystal structure. The inhibitor stabilizes TG2 in an extended conformation that is dramatically different from earlier transglutaminase structures. The active site is exposed, revealing that catalysis takes place in a tunnel, bridged by two tryptophan residues that separate acyl-donor from acyl-acceptor and stabilize the tetrahedral reaction intermediates. Site-directed mutagenesis was used to investigate the acyl-acceptor side of the tunnel, yielding mutants with a marked increase in preference for hydrolysis over transamidation. By providing the ability to visualize this activated conformer, our results create a foundation for understanding the catalytic as well as the non-catalytic roles of TG2 in biology, and for dissecting the process by which the autoantibody response to TG2 is induced in celiac sprue patients.

  12. Conformational equilibria and intrinsic affinities define integrin activation.

    Science.gov (United States)

    Li, Jing; Su, Yang; Xia, Wei; Qin, Yan; Humphries, Martin J; Vestweber, Dietmar; Cabañas, Carlos; Lu, Chafen; Springer, Timothy A

    2017-03-01

    We show that the three conformational states of integrin α5β1 have discrete free energies and define activation by measuring intrinsic affinities for ligand of each state and the equilibria linking them. The 5,000-fold higher affinity of the extended-open state than the bent-closed and extended-closed states demonstrates profound regulation of affinity. Free energy requirements for activation are defined with protein fragments and intact α5β1 On the surface of K562 cells, α5β1 is 99.8% bent-closed. Stabilization of the bent conformation by integrin transmembrane and cytoplasmic domains must be overcome by cellular energy input to stabilize extension. Following extension, headpiece opening is energetically favored. N-glycans and leg domains in each subunit that connect the ligand-binding head to the membrane repel or crowd one another and regulate conformational equilibria in favor of headpiece opening. The results suggest new principles for regulating signaling in the large class of receptors built from extracellular domains in tandem with single-span transmembrane domains.

  13. Temporal (In)Stability of Employee Preferences for Rewards

    Science.gov (United States)

    Wine, Byron; Gilroy, Shawn; Hantula, Donald A.

    2012-01-01

    This study examined the temporal stability of employee preferences for rewards over seven monthly evaluations. Participants completed a ranking stimulus preference assessment monthly, and the latter six monthly assessments were compared to the initial assessment. Correlations of preferences from month to month ranged from r = -0.89 to 0.99.…

  14. Evidence for Weak or Linear Conformity but Not for Hyper-Conformity in an Everyday Social Learning Context

    Science.gov (United States)

    Claidière, Nicolas; Bowler, Mark; Whiten, Andrew

    2012-01-01

    Conformity is thought to be an important force in cultural evolution because it has the potential to stabilize cooperation in large groups, potentiate group selection and thus explain uniquely human behaviors. However, the effects of such conformity on cultural and biological evolution will depend much on the way individuals are influenced by the frequency of alternative behavioral options witnessed. Theoretical modeling has suggested that only what we refer to as ‘hyper-conformity’, an exaggerated tendency to perform the most frequent behavior witnessed in other individuals, is able to increase within-group homogeneity and between-group diversity, for instance. Empirically however, few experiments have addressed how the frequency of behavior witnessed affects behavior. Accordingly we performed an experiment to test for the presence of conformity in a natural situation with humans. Visitors to a Zoo exhibit were invited to write or draw answers to questions on A5 cards and potentially win a small prize. We manipulated the proportion of existing writings versus drawings visible to visitors and measured the proportion of written cards submitted. We found a strong and significant effect of the proportion of text displayed on the proportion of text in the answers, thus demonstrating social learning. We show that this effect is approximately linear, with potentially a small, weak-conformist component but no hyper-conformist one. The present experiment therefore provides evidence for linear conformity in humans in a very natural context. PMID:22363524

  15. Rotational Spectroscopy and Conformational Studies of 4-PENTYNENITRILE, 4-PENTENENITRILE, and Glutaronitrile

    Science.gov (United States)

    Hays, Brian M.; Mehta-Hurt, Deepali; Jawad, Khadija M.; Hernandez-Castillo, Alicia O.; Abeysekera, Chamara; Zhang, Di; Zwier, Timothy S.

    2017-06-01

    The pure rotational spectra of 4-pentynenitrile, 4-pentenenitrile, and glutaronitrile were acquired using chirped pulse Fouirer transform microwave spectroscopy. 4-pentynenitrile and 4-pentenenitrile are the recombination products of two resonance stabilized radicals, propargyl + cyanomethyl or allyl + cyanomethyl, respectively, and are thus anticipated to be significant among the more complex nitriles in Titan's atmosphere. Indeed, these partially unsaturated alkyl cyanides have been found in laboratory analogs of tholins and are also expected to have interesting photochemistry. The optimized structures of all conformers below predicted energies of 500 \\wn were calculated for each molecule. Both of the conformers, trans and gauche, for 4-pentynenitrile have been identified and assigned. Five conformers were assigned in 4-pentenenitrile. The eclipsed conformers, with respect to the vinyl group, dominate the spectrum but some population was found in the syn conformers including the syn-gauche conformer, calculated to be 324 \\wn above the global minimum. The glutaronitrile spectrum contained only the two conformers below 500 \\wn, with reduced amount of the gauche trans conformer. The assigned spectra and structural assignments will be presented.

  16. Conformational antibody binding to a native, cell-free expressed GPCR in block copolymer membranes.

    Science.gov (United States)

    de Hoog, Hans-Peter M; Lin JieRong, Esther M; Banerjee, Sourabh; Décaillot, Fabien M; Nallani, Madhavan

    2014-01-01

    G-protein coupled receptors (GPCRs) play a key role in physiological processes and are attractive drug targets. Their biophysical characterization is, however, highly challenging because of their innate instability outside a stabilizing membrane and the difficulty of finding a suitable expression system. We here show the cell-free expression of a GPCR, CXCR4, and its direct embedding in diblock copolymer membranes. The polymer-stabilized CXCR4 is readily immobilized onto biosensor chips for label-free binding analysis. Kinetic characterization using a conformationally sensitive antibody shows the receptor to exist in the correctly folded conformation, showing binding behaviour that is commensurate with heterologously expressed CXCR4.

  17. Conformational antibody binding to a native, cell-free expressed GPCR in block copolymer membranes.

    Directory of Open Access Journals (Sweden)

    Hans-Peter M de Hoog

    Full Text Available G-protein coupled receptors (GPCRs play a key role in physiological processes and are attractive drug targets. Their biophysical characterization is, however, highly challenging because of their innate instability outside a stabilizing membrane and the difficulty of finding a suitable expression system. We here show the cell-free expression of a GPCR, CXCR4, and its direct embedding in diblock copolymer membranes. The polymer-stabilized CXCR4 is readily immobilized onto biosensor chips for label-free binding analysis. Kinetic characterization using a conformationally sensitive antibody shows the receptor to exist in the correctly folded conformation, showing binding behaviour that is commensurate with heterologously expressed CXCR4.

  18. STABILITY ANALYSIS OF A COMPUTER VIRUS PROPAGATION MODEL WITH ANTIDOTE IN VULNERABLE SYSTEM

    Institute of Scientific and Technical Information of China (English)

    Nguyen Huu KHANH; Nguyen Bich HUY

    2016-01-01

    We study a proposed model describing the propagation of computer virus in the network with antidote in vulnerable system. Mathematical analysis shows that dynamics of the spread of computer viruses is determined by the threshold R0. If R0 ≤ 1, the virus-free equilibrium is globally asymptotically stable, and if R0 >1, the endemic equilibrium is globally asymptotically stable. Lyapunov functional method as well as geometric approach are used for proving the global stability of equilibria. A numerical investigation is carried out to confirm the analytical results. Through parameter analysis, some effective strategies for eliminating viruses are suggested.

  19. Synthesis and Conformation Analysis of cis-1,2-Disubstituted Cyclododecanes

    Institute of Scientific and Technical Information of China (English)

    HAN Xiang-Yu; WANG Ming-An; LI Tai-Gong; LIANG Xiao-Mei; DONG Yan-Hong; CHEN Fu-Heng; WANG Dao-Quan

    2007-01-01

    cis-1,2-Disubstituted cyclododecanes 2 were synthesized by sodium borohydride reduction of 2-monosubstituted cyclododecanones and their structures were confirmed by 1HNMR, 13C NMR and elemental analysis. The higher cis-selectivity of NaBH4 reduction of 2- monosubstituted cyclododecanones was rationalized by the mode of "corner position carbonyl participation". Crystal data for 2c: Mr = 263.21, monoclinic, space group P21/c, a = 1.11140(7), b = 2.62590(17), c = 0.91360(6) nm, β= 106.1840(10)°, V = 2.5606(3) nm3, Dc = 1.366 g/cm3, Z = 8, F(000) = 1104, μ(MoKα= 3.182 mm-1, S = 0.837, the final R = 0.0460 and wR = 0.1033. Crystal X-ray diffraction analysis for 2c showed that its ring skeleton adopts [3333] conformation, in which the OH group presents at the side-exo position and the other one at the corner carbon. The 1H NMR data of 2 showed that 1-corner-R-2-side-exo-OH [3333] and 1-corner-OH-2-side-exo-R [3333] conformations coexist in dynamic equilibrium in the solution, but only the former presents in the crystal.

  20. Tibiofemoral joint subchondral surface conformity: Individual variability with race and sex-specific trends.

    Science.gov (United States)

    Everhart, Joshua S; Flanigan, David C; Chaudhari, Ajit M W; Siston, Robert A

    2016-10-01

    Femoral and tibial subchondral surface morphology has been extensively studied to aid in anatomically correct total knee arthroplasty (TKA) implant design. Emphasis has been placed on shape variations in individual bones, and person-to-person variability in joint conformity has been overlooked. The purpose of this study is to 1) determine individual variability in key measures of tibiofemoral joint conformity, and 2) determine whether variability differs by sex or race. Laser-scanner-generated surface models of tibiofemoral joints were obtained from 165 archival skeletons (at death: age 28.8±7.6years; 85 African-American, 80 Caucasian, 86 men, 79 women). Ratios and correlations were determined among related femoral and tibial subchondral surface areas (SA), alignment, curvatures, and linear dimensions between opposing surfaces with stratification by race and sex. Anterior-posterior length (R=0.80, pconformity at the subchondral surface, and for some measures this variability is sex-or-race specific. Key measures of joint conformity including surface area, curvature, width, and depth covary weakly or not at all, and a wide range of TKA component sizes and shapes would be required to accurately replicate native joint conformity in most people. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Conformal properties of the extremal Schwarzschild de-Sitter spacetime

    CERN Document Server

    Gasperin, Edgar

    2015-01-01

    The conformal structure of the extremal Schwarzschild de-Sitter spacetime is analysed using the extended conformal Einstein field equations. Initial data for an asymptotic initial value problem for the extremal Schwarzschild de-Sitter spacetime is obtained. Using the insights gained from the analysis of the reference spacetime we consider nonlinear perturbations close to the extremal Schwarzschild de-Sitter spacetime. We show that small enough perturbations of initial data for the extremal Schwarzschild de-Sitter spacetime, away from the singularity, give rise to a solution to the Einstein field equations which exists to the future and has an asymptotic structure similar to that of the extremal Schwarzschild de-Sitter spacetime. Similarly, we obtain an existence and stability result for asymptotic initial data close to that of the extremal Schwarzschild de-Sitter spacetime in the non-singular region.

  2. Modelling proteins' hidden conformations to predict antibiotic resistance

    Science.gov (United States)

    Hart, Kathryn M.; Ho, Chris M. W.; Dutta, Supratik; Gross, Michael L.; Bowman, Gregory R.

    2016-10-01

    TEM β-lactamase confers bacteria with resistance to many antibiotics and rapidly evolves activity against new drugs. However, functional changes are not easily explained by differences in crystal structures. We employ Markov state models to identify hidden conformations and explore their role in determining TEM's specificity. We integrate these models with existing drug-design tools to create a new technique, called Boltzmann docking, which better predicts TEM specificity by accounting for conformational heterogeneity. Using our MSMs, we identify hidden states whose populations correlate with activity against cefotaxime. To experimentally detect our predicted hidden states, we use rapid mass spectrometric footprinting and confirm our models' prediction that increased cefotaxime activity correlates with reduced Ω-loop flexibility. Finally, we design novel variants to stabilize the hidden cefotaximase states, and find their populations predict activity against cefotaxime in vitro and in vivo. Therefore, we expect this framework to have numerous applications in drug and protein design.

  3. 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.)

  4. 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

  5. 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.

  6. 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

  7. Ideal Stabilization

    CERN Document Server

    Nesterenko, Mikhail

    2009-01-01

    We define and explore the concept of ideal stabilization. The program is ideally stabilizing if its every state is legitimate. Ideal stabilization allows the specification designer to prescribe with arbitrary degree of precision not only the fault-free program behavior but also its recovery operation. Specifications may or may not mention all possible states. We identify approaches to designing ideal stabilization to both kinds of specifications. For the first kind, we state the necessary condition for an ideally stabilizing solution. On the basis of this condition we prove that there is no ideally stabilizing solution to the leader election problem. We illustrate the utility of the concept by providing examples of well-known programs and proving them ideally stabilizing. Specifically, we prove ideal stabilization of the conflict manager, the alternator, the propagation of information with feedback and the alternating bit protocol.

  8. From conformal to Einstein gravity

    Science.gov (United States)

    Anastasiou, Giorgos; Olea, Rodrigo

    2016-10-01

    We provide a simple derivation of the equivalence between Einstein and conformal gravity (CG) with Neumann boundary conditions given by Maldacena. As Einstein spacetimes are Bach flat, a generic solution to CG would contain both Einstein and non-Einstein parts. Using this decomposition of the spacetime curvature in the Weyl tensor makes manifest the equivalence between the two theories, both at the level of the action and the variation of it. As a consequence, we show that the on-shell action for critical gravity in four dimensions is given uniquely in terms of the Bach tensor.

  9. From Conformal to Einstein Gravity

    CERN Document Server

    Anastasiou, Giorgos

    2016-01-01

    We provide a simple derivation of the equivalence between Einstein and Conformal Gravity (CG) with Neumann boundary conditions given by Maldacena. As Einstein spacetimes are Bach flat, a generic solution to CG would contain both Einstein and non-Einstein part. Using this decomposition of the spacetime curvature in the Weyl tensor, makes manifest the equivalence between the two theories, both at the level of the action and the variation of it. As a consequence, we show that the on-shell action for Critical Gravity in four dimensions is given uniquely in terms of the Bach tensor.

  10. Toward TeV Conformality

    Energy Technology Data Exchange (ETDEWEB)

    Appelquist, T; Avakian, A; Babich, R; Brower, R C; Cheng, M; Clark, M A; Cohen, S D; Fleming, G T; Kiskis, J; Neil, E T; Osborn, J C; Rebbi, C; Schaich, D; Soltz, R; Vranas, P

    2009-11-30

    We study the chiral condensate <{bar {psi}}{psi}> for an SU(3) gauge theory with N{sub f} massless Dirac fermions in the fundamental representation when N{sub f} is increased from 2 to 6. For N{sub f} = 2, our lattice simulations of <{bar {psi}}{psi}>/F{sup 3}, where F is the Nambu-Goldstone-boson decay constant, agree with the measured QCD value. For N{sub f} = 6, this ratio shows significant enhancement, presaging an even larger enhancement anticipated as N{sub f} increases further, toward the critical value for transition from confinement to infrared conformality.

  11. Measurement of the ratio of inclusive jet cross sections using the anti-$k_T$ algorithm with radius parameters R=0.5 and 0.7 in pp collisions at $\\sqrt{s}$ = 7 TeV

    CERN Document Server

    Chatrchyan, Serguei; Sirunyan, Albert M; Tumasyan, Armen; Adam, Wolfgang; Bergauer, Thomas; Dragicevic, Marko; Erö, Janos; Fabjan, Christian; Friedl, Markus; Fruehwirth, Rudolf; Ghete, Vasile Mihai; Hartl, Christian; Hörmann, Natascha; Hrubec, Josef; Jeitler, Manfred; Kiesenhofer, Wolfgang; Knünz, Valentin; Krammer, Manfred; Krätschmer, Ilse; Liko, Dietrich; Mikulec, Ivan; Rabady, Dinyar; Rahbaran, Babak; Rohringer, Herbert; Schöfbeck, Robert; Strauss, Josef; Taurok, Anton; Treberer-Treberspurg, Wolfgang; Waltenberger, Wolfgang; Wulz, Claudia-Elisabeth; Mossolov, Vladimir; Shumeiko, Nikolai; Suarez Gonzalez, Juan; Alderweireldt, Sara; Bansal, Monika; Bansal, Sunil; Cornelis, Tom; De Wolf, Eddi A; Janssen, Xavier; Knutsson, Albert; Luyckx, Sten; Mucibello, Luca; Ochesanu, Silvia; Roland, Benoit; Rougny, Romain; Van Haevermaet, Hans; Van Mechelen, Pierre; Van Remortel, Nick; Van Spilbeeck, Alex; Blekman, Freya; Blyweert, Stijn; D'Hondt, Jorgen; Heracleous, Natalie; Kalogeropoulos, Alexis; Keaveney, James; Kim, Tae Jeong; Lowette, Steven; Maes, Michael; Olbrechts, Annik; Strom, Derek; Tavernier, Stefaan; Van Doninck, Walter; Van Mulders, Petra; Van Onsem, Gerrit Patrick; Villella, Ilaria; Caillol, Cécile; Clerbaux, Barbara; De Lentdecker, Gilles; Favart, Laurent; Gay, Arnaud; Léonard, Alexandre; Marage, Pierre Edouard; Mohammadi, Abdollah; Perniè, Luca; Reis, Thomas; Seva, Tomislav; Thomas, Laurent; Vander Velde, Catherine; Vanlaer, Pascal; Wang, Jian; Adler, Volker; Beernaert, Kelly; Benucci, Leonardo; Cimmino, Anna; Costantini, Silvia; Dildick, Sven; Garcia, Guillaume; Klein, Benjamin; Lellouch, Jérémie; Mccartin, Joseph; Ocampo Rios, Alberto Andres; Ryckbosch, Dirk; Salva Diblen, Sinem; Sigamani, Michael; Strobbe, Nadja; Thyssen, Filip; Tytgat, Michael; Walsh, Sinead; Yazgan, Efe; Zaganidis, Nicolas; Basegmez, Suzan; Beluffi, Camille; Bruno, Giacomo; Castello, Roberto; Caudron, Adrien; Ceard, Ludivine; Da Silveira, Gustavo Gil; Delaere, Christophe; Du Pree, Tristan; Favart, Denis; Forthomme, Laurent; Giammanco, Andrea; Hollar, Jonathan; Jez, Pavel; Komm, Matthias; Lemaitre, Vincent; Liao, Junhui; Militaru, Otilia; Nuttens, Claude; Pagano, Davide; Pin, Arnaud; Piotrzkowski, Krzysztof; Popov, Andrey; Quertenmont, Loic; Selvaggi, Michele; Vidal Marono, Miguel; Vizan Garcia, Jesus Manuel; Beliy, Nikita; Caebergs, Thierry; Daubie, Evelyne; Hammad, Gregory Habib; Alves, Gilvan; Correa Martins Junior, Marcos; Dos Reis Martins, Thiago; Pol, Maria Elena; Henrique Gomes E Souza, Moacyr; Aldá Júnior, Walter Luiz; Carvalho, Wagner; Chinellato, Jose; Custódio, Analu; Melo Da Costa, Eliza; De Jesus Damiao, Dilson; De Oliveira Martins, Carley; Fonseca De Souza, Sandro; Malbouisson, Helena; Malek, Magdalena; Matos Figueiredo, Diego; Mundim, Luiz; Nogima, Helio; Prado Da Silva, Wanda Lucia; Santaolalla, Javier; Santoro, Alberto; Sznajder, Andre; Tonelli Manganote, Edmilson José; Vilela Pereira, Antonio; Bernardes, Cesar Augusto; De Almeida Dias, Flavia; Tomei, Thiago; De Moraes Gregores, Eduardo; Lagana, Caio; Mercadante, Pedro G; Novaes, Sergio F; Padula, Sandra; Genchev, Vladimir; Iaydjiev, Plamen; Marinov, Andrey; Piperov, Stefan; Rodozov, Mircho; Sultanov, Georgi; Vutova, Mariana; Dimitrov, Anton; Glushkov, Ivan; Hadjiiska, Roumyana; Kozhuharov, Venelin; Litov, Leander; Pavlov, Borislav; Petkov, Peicho; Bian, Jian-Guo; Chen, Guo-Ming; Chen, He-Sheng; Chen, Mingshui; Du, Ran; Jiang, Chun-Hua; Liang, Dong; Liang, Song; Meng, Xiangwei; Plestina, Roko; Tao, Junquan; Wang, Xianyou; Wang, Zheng; Asawatangtrakuldee, Chayanit; Ban, Yong; Guo, Yifei; Li, Qiang; Li, Wenbo; Liu, Shuai; Mao, Yajun; Qian, Si-Jin; Wang, Dayong; Zhang, Linlin; Zou, Wei; Avila, Carlos; Carrillo Montoya, Camilo Andres; Chaparro Sierra, Luisa Fernanda; Florez, Carlos; Gomez, Juan Pablo; Gomez Moreno, Bernardo; Sanabria, Juan Carlos; Godinovic, Nikola; Lelas, Damir; Polic, Dunja; Puljak, Ivica; Antunovic, Zeljko; Kovac, Marko; Brigljevic, Vuko; Kadija, Kreso; Luetic, Jelena; Mekterovic, Darko; Morovic, Srecko; Sudic, Lucija; Attikis, Alexandros; Mavromanolakis, Georgios; Mousa, Jehad; Nicolaou, Charalambos; Ptochos, Fotios; Razis, Panos A; Finger, Miroslav; Finger Jr, Michael; Abdelalim, Ahmed Ali; Assran, Yasser; Elgammal, Sherif; Ellithi Kamel, Ali; Mahmoud, Mohammed; Radi, Amr; Kadastik, Mario; Müntel, Mait; Murumaa, Marion; Raidal, Martti; Rebane, Liis; Tiko, Andres; Eerola, Paula; Fedi, Giacomo; Voutilainen, Mikko; Härkönen, Jaakko; Karimäki, Veikko; Kinnunen, Ritva; Kortelainen, Matti J; Lampén, Tapio; Lassila-Perini, Kati; Lehti, Sami; Lindén, Tomas; Luukka, Panja-Riina; Mäenpää, Teppo; Peltola, Timo; Tuominen, Eija; Tuominiemi, Jorma; Tuovinen, Esa; Wendland, Lauri; Tuuva, Tuure; Besancon, Marc; Couderc, Fabrice; Dejardin, Marc; Denegri, Daniel; Fabbro, Bernard; Faure, Jean-Louis; Ferri, Federico; Ganjour, Serguei; Givernaud, Alain; Gras, Philippe; Hamel de Monchenault, Gautier; Jarry, Patrick; Locci, Elizabeth; Malcles, Julie; Nayak, Aruna; Rander, John; Rosowsky, André; Titov, Maksym; Baffioni, Stephanie; Beaudette, Florian; Busson, Philippe; Charlot, Claude; Daci, Nadir; Dahms, Torsten; Dalchenko, Mykhailo; Dobrzynski, Ludwik; Florent, Alice; Granier de Cassagnac, Raphael; Miné, Philippe; Mironov, Camelia; Naranjo, Ivo Nicolas; Nguyen, Matthew; Ochando, Christophe; Paganini, Pascal; Sabes, David; Salerno, Roberto; Sirois, Yves; Veelken, Christian; Yilmaz, Yetkin; Zabi, Alexandre; Agram, Jean-Laurent; Andrea, Jeremy; Bloch, Daniel; Brom, Jean-Marie; Chabert, Eric Christian; Collard, Caroline; Conte, Eric; Drouhin, Frédéric; Fontaine, Jean-Charles; Gelé, Denis; Goerlach, Ulrich; Goetzmann, Christophe; Juillot, Pierre; Le Bihan, Anne-Catherine; Van Hove, Pierre; Gadrat, Sébastien; Beauceron, Stephanie; Beaupere, Nicolas; Boudoul, Gaelle; Brochet, Sébastien; Chasserat, Julien; Chierici, Roberto; Contardo, Didier; Depasse, Pierre; El Mamouni, Houmani; Fan, Jiawei; Fay, Jean; Gascon, Susan; Gouzevitch, Maxime; Ille, Bernard; Kurca, Tibor; Lethuillier, Morgan; Mirabito, Laurent; Perries, Stephane; Ruiz Alvarez, José David; Sgandurra, Louis; Sordini, Viola; Vander Donckt, Muriel; Verdier, Patrice; Viret, Sébastien; Xiao, Hong; Tsamalaidze, Zviad; Autermann, Christian; Beranek, Sarah; Bontenackels, Michael; Calpas, Betty; Edelhoff, Matthias; Feld, Lutz; Hindrichs, Otto; Klein, Katja; Ostapchuk, Andrey; Perieanu, Adrian; Raupach, Frank; Sammet, Jan; Schael, Stefan; Sprenger, Daniel; Weber, Hendrik; Wittmer, Bruno; Zhukov, Valery; Ata, Metin; Caudron, Julien; Dietz-Laursonn, Erik; Duchardt, Deborah; Erdmann, Martin; Fischer, Robert; Güth, Andreas; Hebbeker, Thomas; Heidemann, Carsten; Hoepfner, Kerstin; Klingebiel, Dennis; Knutzen, Simon; Kreuzer, Peter; Merschmeyer, Markus; Meyer, Arnd; Olschewski, Mark; Padeken, Klaas; Papacz, Paul; Reithler, Hans; Schmitz, Stefan Antonius; Sonnenschein, Lars; Teyssier, Daniel; Thüer, Sebastian; Weber, Martin; Cherepanov, Vladimir; Erdogan, Yusuf; Flügge, Günter; Geenen, Heiko; Geisler, Matthias; Haj Ahmad, Wael; Hoehle, Felix; Kargoll, Bastian; Kress, Thomas; Kuessel, Yvonne; Lingemann, Joschka; Nowack, Andreas; Nugent, Ian Michael; Perchalla, Lars; Pooth, Oliver; Stahl, Achim; Asin, Ivan; Bartosik, Nazar; Behr, Joerg; Behrenhoff, Wolf; Behrens, Ulf; Bell, Alan James; Bergholz, Matthias; Bethani, Agni; Borras, Kerstin; Burgmeier, Armin; Cakir, Altan; Calligaris, Luigi; Campbell, Alan; Choudhury, Somnath; Costanza, Francesco; Diez Pardos, Carmen; Dooling, Samantha; Dorland, Tyler; Eckerlin, Guenter; Eckstein, Doris; Eichhorn, Thomas; Flucke, Gero; Geiser, Achim; Grebenyuk, Anastasia; Gunnellini, Paolo; Habib, Shiraz; Hauk, Johannes; Hellwig, Gregor; Hempel, Maria; Horton, Dean; Jung, Hannes; Kasemann, Matthias; Katsas, Panagiotis; Kieseler, Jan; Kleinwort, Claus; Krämer, Mira; Krücker, Dirk; Lange, Wolfgang; Leonard, Jessica; Lipka, Katerina; Lohmann, Wolfgang; Lutz, Benjamin; Mankel, Rainer; Marfin, Ihar; Melzer-Pellmann, Isabell-Alissandra; Meyer, Andreas Bernhard; Mnich, Joachim; Mussgiller, Andreas; Naumann-Emme, Sebastian; Novgorodova, Olga; Nowak, Friederike; Perrey, Hanno; Petrukhin, Alexey; Pitzl, Daniel; Placakyte, Ringaile; Raspereza, Alexei; Ribeiro Cipriano, Pedro M; Riedl, Caroline; Ron, Elias; Sahin, Mehmet Özgür; Salfeld-Nebgen, Jakob; Saxena, Pooja; Schmidt, Ringo; Schoerner-Sadenius, Thomas; Schröder, Matthias; Stein, Matthias; Vargas Trevino, Andrea Del Rocio; Walsh, Roberval; Wissing, Christoph; Aldaya Martin, Maria; Blobel, Volker; Enderle, Holger; Erfle, Joachim; Garutti, Erika; Goebel, Kristin; Görner, Martin; Gosselink, Martijn; Haller, Johannes; Höing, Rebekka Sophie; Kirschenmann, Henning; Klanner, Robert; Kogler, Roman; Lange, Jörn; Lapsien, Tobias; Lenz, Teresa; Marchesini, Ivan; Ott, Jochen; Peiffer, Thomas; Pietsch, Niklas; Rathjens, Denis; Sander, Christian; Schettler, Hannes; Schleper, Peter; Schlieckau, Eike; Schmidt, Alexander; Seidel, Markus; Poehlsen, Jennifer; Sola, Valentina; Stadie, Hartmut; Steinbrück, Georg; Troendle, Daniel; Usai, Emanuele; Vanelderen, Lukas; Barth, Christian; Baus, Colin; Berger, Joram; Böser, Christian; Butz, Erik; Chwalek, Thorsten; De Boer, Wim; Descroix, Alexis; Dierlamm, Alexander; Feindt, Michael; Guthoff, Moritz; Hartmann, Frank; Hauth, Thomas; Held, Hauke; Hoffmann, Karl-Heinz; Husemann, Ulrich; Katkov, Igor; Kornmayer, Andreas; Kuznetsova, Ekaterina; Lobelle Pardo, Patricia; Martschei, Daniel; Mozer, Matthias Ulrich; Müller, Thomas; Niegel, Martin; Nürnberg, Andreas; Oberst, Oliver; Quast, Gunter; Rabbertz, Klaus; Ratnikov, Fedor; Röcker, Steffen; Schilling, Frank-Peter; Schott, Gregory; Simonis, Hans-Jürgen; Stober, Fred-Markus Helmut; Ulrich, Ralf; Wagner-Kuhr, Jeannine; Wayand, Stefan; Weiler, Thomas; Wolf, Roger; Zeise, Manuel; Anagnostou, Georgios; Daskalakis, Georgios; Geralis, Theodoros; Kesisoglou, Stilianos; Kyriakis, Aristotelis; Loukas, Demetrios; Markou, Athanasios; Markou, Christos; Ntomari, Eleni; Psallidas, Andreas; Topsis-Giotis, Iasonas; Gouskos, Loukas; Panagiotou, Apostolos; Saoulidou, Niki; Stiliaris, Efstathios; Aslanoglou, Xenofon; Evangelou, Ioannis; Flouris, Giannis; Foudas, Costas; Jones, John; Kokkas, Panagiotis; Manthos, Nikolaos; Papadopoulos, Ioannis; Paradas, Evangelos; Bencze, Gyorgy; Hajdu, Csaba; Hidas, Pàl; Horvath, Dezso; Sikler, Ferenc; Veszpremi, Viktor; Vesztergombi, Gyorgy; Zsigmond, Anna Julia; Beni, Noemi; Czellar, Sandor; Molnar, Jozsef; Palinkas, Jozsef; Szillasi, Zoltan; Karancsi, János; Raics, Peter; Trocsanyi, Zoltan Laszlo; Ujvari, Balazs; Swain, Sanjay Kumar; Beri, Suman Bala; Bhatnagar, Vipin; Dhingra, Nitish; Gupta, Ruchi; Kaur, Manjit; Mehta, Manuk Zubin; Mittal, Monika; Nishu, Nishu; Sharma, Archana; Singh, Jasbir; Kumar, Ashok; Kumar, Arun; Ahuja, Sudha; Bhardwaj, Ashutosh; Choudhary, Brajesh C; Kumar, Ajay; Malhotra, Shivali; Naimuddin, Md; Ranjan, Kirti; Sharma, Varun; Shivpuri, Ram Krishen; Banerjee, Sunanda; Bhattacharya, Satyaki; Chatterjee, Kalyanmoy; Dutta, Suchandra; Gomber, Bhawna; Jain, Sandhya; Jain, Shilpi; Khurana, Raman; Modak, Atanu; Mukherjee, Swagata; Roy, Debarati; Sarkar, Subir; Sharan, Manoj; Singh, Anil; Abdulsalam, Abdulla; Dutta, Dipanwita; Kailas, Swaminathan; Kumar, Vineet; Mohanty, Ajit Kumar; Pant, Lalit Mohan; Shukla, Prashant; Topkar, Anita; Aziz, Tariq; Banerjee, Sudeshna; Chatterjee, Rajdeep Mohan; Dugad, Shashikant; Ganguly, Sanmay; Ghosh, Saranya; Guchait, Monoranjan; Gurtu, Atul; Kole, Gouranga; Kumar, Sanjeev; Maity, Manas; Majumder, Gobinda; Mazumdar, Kajari; Mohanty, Gagan Bihari; Parida, Bibhuti; Sudhakar, Katta; Wickramage, Nadeesha; Arfaei, Hessamaddin; Bakhshiansohi, Hamed; Behnamian, Hadi; Etesami, Seyed Mohsen; Fahim, Ali; Jafari, Abideh; Khakzad, Mohsen; Mohammadi Najafabadi, Mojtaba; Naseri, Mohsen; Paktinat Mehdiabadi, Saeid; Safarzadeh, Batool; Zeinali, Maryam; Grunewald, Martin; Abbrescia, Marcello; Barbone, Lucia; Calabria, Cesare; Chhibra, Simranjit Singh; Colaleo, Anna; Creanza, Donato; De Filippis, Nicola; De Palma, Mauro; Fiore, Luigi; Iaselli, Giuseppe; Maggi, Giorgio; Maggi, Marcello; Marangelli, Bartolomeo; My, Salvatore; Nuzzo, Salvatore; Pacifico, Nicola; Pompili, Alexis; Pugliese, Gabriella; Radogna, Raffaella; Selvaggi, Giovanna; Silvestris, Lucia; Singh, Gurpreet; Venditti, Rosamaria; Verwilligen, Piet; Zito, Giuseppe; Abbiendi, Giovanni; Benvenuti, Alberto; Bonacorsi, Daniele; Braibant-Giacomelli, Sylvie; Brigliadori, Luca; Campanini, Renato; Capiluppi, Paolo; Castro, Andrea; Cavallo, Francesca Romana; Codispoti, Giuseppe; Cuffiani, Marco; Dallavalle, Gaetano-Marco; Fabbri, Fabrizio; Fanfani, Alessandra; Fasanella, Daniele; Giacomelli, Paolo; Grandi, Claudio; Guiducci, Luigi; Marcellini, Stefano; Masetti, Gianni; Meneghelli, Marco; Montanari, Alessandro; Navarria, Francesco; Odorici, Fabrizio; Perrotta, Andrea; Primavera, Federica; Rossi, Antonio; Rovelli, Tiziano; Siroli, Gian Piero; Tosi, Nicolò; Travaglini, Riccardo; Albergo, Sebastiano; Cappello, Gigi; Chiorboli, Massimiliano; Costa, Salvatore; Giordano, Ferdinando; Potenza, Renato; Tricomi, Alessia; Tuve, Cristina; Barbagli, Giuseppe; Ciulli, Vitaliano; Civinini, Carlo; D'Alessandro, Raffaello; Focardi, Ettore; Gallo, Elisabetta; Gonzi, Sandro; Gori, Valentina; Lenzi, Piergiulio; Meschini, Marco; Paoletti, Simone; Sguazzoni, Giacomo; Tropiano, Antonio; Benussi, Luigi; Bianco, Stefano; Fabbri, Franco; Piccolo, Davide; Fabbricatore, Pasquale; Ferretti, Roberta; Ferro, Fabrizio; Lo Vetere, Maurizio; Musenich, Riccardo; Robutti, Enrico; Tosi, Silvano; Benaglia, Andrea; Dinardo, Mauro Emanuele; Fiorendi, Sara; Gennai, Simone; Gerosa, Raffaele; Ghezzi, Alessio; Govoni, Pietro; Lucchini, Marco Toliman; Malvezzi, Sandra; Manzoni, Riccardo Andrea; Martelli, Arabella; Marzocchi, Badder; Menasce, Dario; Moroni, Luigi; Paganoni, Marco; Pedrini, Daniele; Ragazzi, Stefano; Redaelli, Nicola; Tabarelli de Fatis, Tommaso; Buontempo, Salvatore; Cavallo, Nicola; Fabozzi, Francesco; Iorio, Alberto Orso Maria; Lista, Luca; Meola, Sabino; Merola, Mario; Paolucci, Pierluigi; Azzi, Patrizia; Bacchetta, Nicola; Bellato, Marco; Biasotto, Massimo; Bisello, Dario; Branca, Antonio; Checchia, Paolo; Dorigo, Tommaso; Dosselli, Umberto; Fanzago, Federica; Galanti, Mario; Gasparini, Fabrizio; Giubilato, Piero; Gozzelino, Andrea; Kanishchev, Konstantin; Lacaprara, Stefano; Lazzizzera, Ignazio; Margoni, Martino; Meneguzzo, Anna Teresa; Pazzini, Jacopo; Pozzobon, Nicola; Ronchese, Paolo; Simonetto, Franco; Torassa, Ezio; Tosi, Mia; Vanini, Sara; Zotto, Pierluigi; Zucchetta, Alberto; Zumerle, Gianni; Gabusi, Michele; Ratti, Sergio P; Riccardi, Cristina; Vitulo, Paolo; Biasini, Maurizio; Bilei, Gian Mario; Fanò, Livio; Lariccia, Paolo; Mantovani, Giancarlo; Menichelli, Mauro; Romeo, Francesco; Saha, Anirban; Santocchia, Attilio; Spiezia, Aniello; Androsov, Konstantin; Azzurri, Paolo; Bagliesi, Giuseppe; Bernardini, Jacopo; Boccali, Tommaso; Broccolo, Giuseppe; Castaldi, Rino; Ciocci, Maria Agnese; Dell'Orso, Roberto; Fiori, Francesco; Foà, Lorenzo; Giassi, Alessandro; Grippo, Maria Teresa; Kraan, Aafke; Ligabue, Franco; Lomtadze, Teimuraz; Martini, Luca; Messineo, Alberto; Moon, Chang-Seong; Palla, Fabrizio; Rizzi, Andrea; Savoy-Navarro, Aurore; Serban, Alin Titus; Spagnolo, Paolo; Squillacioti, Paola; Tenchini, Roberto; Tonelli, Guido; Venturi, Andrea; Verdini, Piero Giorgio; Vernieri, Caterina; Barone, Luciano; Cavallari, Francesca; Del Re, Daniele; Diemoz, Marcella; Grassi, Marco; Jorda, Clara; Longo, Egidio; Margaroli, Fabrizio; Meridiani, Paolo; Micheli, Francesco; Nourbakhsh, Shervin; Organtini, Giovanni; Paramatti, Riccardo; Rahatlou, Shahram; Rovelli, Chiara; Soffi, Livia; Traczyk, Piotr; Amapane, Nicola; Arcidiacono, Roberta; Argiro, Stefano; Arneodo, Michele; Bellan, Riccardo; Biino, Cristina; Cartiglia, Nicolo; Casasso, Stefano; Costa, Marco; Degano, Alessandro; Demaria, Natale; Mariotti, Chiara; Maselli, Silvia; Migliore, Ernesto; Monaco, Vincenzo; Musich, Marco; Obertino, Maria Margherita; Ortona, Giacomo; Pacher, Luca; Pastrone, Nadia; Pelliccioni, Mario; Potenza, Alberto; Romero, Alessandra; Ruspa, Marta; Sacchi, Roberto; Solano, Ada; Staiano, Amedeo; Tamponi, Umberto; Belforte, Stefano; Candelise, Vieri; Casarsa, Massimo; Cossutti, Fabio; Della Ricca, Giuseppe; Gobbo, Benigno; La Licata, Chiara; Marone, Matteo; Montanino, Damiana; Penzo, Aldo; Schizzi, Andrea; Umer, Tomo; Zanetti, Anna; Chang, Sunghyun; Kim, Tae Yeon; Nam, Soon-Kwon; Kim, Dong Hee; Kim, Gui Nyun; Kim, Ji Eun; Kim, Min Suk; Kong, Dae Jung; Lee, Sangeun; Oh, Young Do; Park, Hyangkyu; Son, Dong-Chul; Kim, Jae Yool; Kim, Zero Jaeho; Song, Sanghyeon; Choi, Suyong; Gyun, Dooyeon; Hong, Byung-Sik; Jo, Mihee; Kim, Hyunchul; Kim, Yongsun; Lee, Kyong Sei; Park, Sung Keun; Roh, Youn; Choi, Minkyoo; Kim, Ji Hyun; Park, Chawon; Park, Inkyu; Park, Sangnam; Ryu, Geonmo; Choi, Young-Il; Choi, Young Kyu; Goh, Junghwan; Kwon, Eunhyang; Lee, Byounghoon; Lee, Jongseok; Seo, Hyunkwan; Yu, Intae; Juodagalvis, Andrius; Komaragiri, Jyothsna Rani; Castilla-Valdez, Heriberto; De La Cruz-Burelo, Eduard; Heredia-de La Cruz, Ivan; Lopez-Fernandez, Ricardo; Martínez-Ortega, Jorge; Sánchez Hernández, Alberto; Villasenor-Cendejas, Luis Manuel; Carrillo Moreno, Salvador; Vazquez Valencia, Fabiola; Salazar Ibarguen, Humberto Antonio; Casimiro Linares, Edgar; Morelos Pineda, Antonio; Krofcheck, David; Butler, Philip H; Doesburg, Robert; Reucroft, Steve; Ahmad, Muhammad; Asghar, Muhammad Irfan; Butt, Jamila; Hoorani, Hafeez R; Khan, Wajid Ali; Khurshid, Taimoor; Qazi, Shamona; Shah, Mehar Ali; Shoaib, Muhammad; Bialkowska, Helena; Bluj, Michal; Boimska, Bożena; Frueboes, Tomasz; Górski, Maciej; Kazana, Malgorzata; Nawrocki, Krzysztof; Romanowska-Rybinska, Katarzyna; Szleper, Michal; Wrochna, Grzegorz; Zalewski, Piotr; Brona, Grzegorz; Bunkowski, Karol; Cwiok, Mikolaj; Dominik, Wojciech; Doroba, Krzysztof; Kalinowski, Artur; Konecki, Marcin; Krolikowski, Jan; Misiura, Maciej; Wolszczak, Weronika; Bargassa, Pedrame; Beirão Da Cruz E Silva, Cristóvão; Faccioli, Pietro; Ferreira Parracho, Pedro Guilherme; Gallinaro, Michele; Nguyen, Federico; Rodrigues Antunes, Joao; Seixas, Joao; Varela, Joao; Vischia, Pietro; Golutvin, Igor; Karjavin, Vladimir; Konoplyanikov, Viktor; Korenkov, Vladimir; Kozlov, Guennady; Lanev, Alexander; Malakhov, Alexander; Matveev, Viktor; Mitsyn, Valeri Valentinovitch; Moisenz, Petr; Palichik, Vladimir; Perelygin, Victor; Shmatov, Sergey; Shulha, Siarhei; Skatchkov, Nikolai; Smirnov, Vitaly; Tikhonenko, Elena; Zarubin, Anatoli; Golovtsov, Victor; Ivanov, Yury; Kim, Victor; Levchenko, Petr; Murzin, Victor; Oreshkin, Vadim; Smirnov, Igor; Sulimov, Valentin; Uvarov, Lev; Vavilov, Sergey; Vorobyev, Alexey; Vorobyev, Andrey; Andreev, Yuri; Dermenev, Alexander; Gninenko, Sergei; Golubev, Nikolai; Kirsanov, Mikhail; Krasnikov, Nikolai; Pashenkov, Anatoli; Tlisov, Danila; Toropin, Alexander; Epshteyn, Vladimir; Gavrilov, Vladimir; Lychkovskaya, Natalia; Popov, Vladimir; Safronov, Grigory; Semenov, Sergey; Spiridonov, Alexander; Stolin, Viatcheslav; Vlasov, Evgueni; Zhokin, Alexander; Andreev, Vladimir; Azarkin, Maksim; Dremin, Igor; Kirakosyan, Martin; Leonidov, Andrey; Mesyats, Gennady; Rusakov, Sergey V; Vinogradov, Alexey; Belyaev, Andrey; Boos, Edouard; Dubinin, Mikhail; Dudko, Lev; Ershov, Alexander; Gribushin, Andrey; Klyukhin, Vyacheslav; Kodolova, Olga; Lokhtin, Igor; Obraztsov, Stepan; Petrushanko, Sergey; Savrin, Viktor; Snigirev, Alexander; Azhgirey, Igor; Bayshev, Igor; Bitioukov, Sergei; Kachanov, Vassili; Kalinin, Alexey; Konstantinov, Dmitri; Krychkine, Victor; Petrov, Vladimir; Ryutin, Roman; Sobol, Andrei; Tourtchanovitch, Leonid; Troshin, Sergey; Tyurin, Nikolay; Uzunian, Andrey; Volkov, Alexey; Adzic, Petar; Dordevic, Milos; Ekmedzic, Marko; Milosevic, Jovan; Aguilar-Benitez, Manuel; Alcaraz Maestre, Juan; Battilana, Carlo; Calvo, Enrique; Cerrada, Marcos; Chamizo Llatas, Maria; Colino, Nicanor; De La Cruz, Begona; Delgado Peris, Antonio; Domínguez Vázquez, Daniel; Fernandez Bedoya, Cristina; Fernández Ramos, Juan Pablo; Ferrando, Antonio; Flix, Jose; Fouz, Maria Cruz; Garcia-Abia, Pablo; Gonzalez Lopez, Oscar; Goy Lopez, Silvia; Hernandez, Jose M; Josa, Maria Isabel; Merino, Gonzalo; Navarro De Martino, Eduardo; Puerta Pelayo, Jesus; Quintario Olmeda, Adrián; Redondo, Ignacio; Romero, Luciano; Senghi Soares, Mara; Willmott, Carlos; Albajar, Carmen; de Trocóniz, Jorge F; Missiroli, Marino; Brun, Hugues; Cuevas, Javier; Fernandez Menendez, Javier; Folgueras, Santiago; Gonzalez Caballero, Isidro; Lloret Iglesias, Lara; Brochero Cifuentes, Javier Andres; Cabrillo, Iban Jose; Calderon, Alicia; Chuang, Shan-Huei; Duarte Campderros, Jordi; Fernandez, Marcos; Gomez, Gervasio; Gonzalez Sanchez, Javier; Graziano, Alberto; Lopez Virto, Amparo; Marco, Jesus; Marco, Rafael; Martinez Rivero, Celso; Matorras, Francisco; Munoz Sanchez, Francisca Javiela; Piedra Gomez, Jonatan; Rodrigo, Teresa; Rodríguez-Marrero, Ana Yaiza; Ruiz-Jimeno, Alberto; Scodellaro, Luca; Vila, Ivan; Vilar Cortabitarte, Rocio; Abbaneo, Duccio; Auffray, Etiennette; Auzinger, Georg; Bachtis, Michail; Baillon, Paul; Ball, Austin; Barney, David; Bendavid, Joshua; Benhabib, Lamia; Benitez, Jose F; Bernet, Colin; Bianchi, Giovanni; Bloch, Philippe; Bocci, Andrea; Bonato, Alessio; Bondu, Olivier; Botta, Cristina; Breuker, Horst; Camporesi, Tiziano; Cerminara, Gianluca; Christiansen, Tim; Coarasa Perez, Jose Antonio; Colafranceschi, Stefano; D'Alfonso, Mariarosaria; D'Enterria, David; Dabrowski, Anne; David Tinoco Mendes, Andre; De Guio, Federico; De Roeck, Albert; De Visscher, Simon; Di Guida, Salvatore; Dobson, Marc; Dupont-Sagorin, Niels; Elliott-Peisert, Anna; Eugster, Jürg; Franzoni, Giovanni; Funk, Wolfgang; Giffels, Manuel; Gigi, Dominique; Gill, Karl; Giordano, Domenico; Girone, Maria; Giunta, Marina; Glege, Frank; Gomez-Reino Garrido, Robert; Gowdy, Stephen; Guida, Roberto; Hammer, Josef; Hansen, Magnus; Harris, Philip; Innocente, Vincenzo; Janot, Patrick; Karavakis, Edward; Kousouris, Konstantinos; Krajczar, Krisztian; Lecoq, Paul; Lourenco, Carlos; Magini, Nicolo; Malgeri, Luca; Mannelli, Marcello; Masetti, Lorenzo; Meijers, Frans; Mersi, Stefano; Meschi, Emilio; Moortgat, Filip; Mulders, Martijn; Musella, Pasquale; Orsini, Luciano; Palencia Cortezon, Enrique; Perez, Emmanuelle; Perrozzi, Luca; Petrilli, Achille; Petrucciani, Giovanni; Pfeiffer, Andreas; Pierini, Maurizio; Pimiä, Martti; Piparo, Danilo; Plagge, Michael; Racz, Attila; Reece, William; Rolandi, Gigi; Rovere, Marco; Sakulin, Hannes; Santanastasio, Francesco; Schäfer, Christoph; Schwick, Christoph; Sekmen, Sezen; Sharma, Archana; Siegrist, Patrice; Silva, Pedro; Simon, Michal; Sphicas, Paraskevas; Spiga, Daniele; Steggemann, Jan; Stieger, Benjamin; Stoye, Markus; Tsirou, Andromachi; Veres, Gabor Istvan; Vlimant, Jean-Roch; Wöhri, Hermine Katharina; Zeuner, Wolfram Dietrich; Bertl, Willi; Deiters, Konrad; Erdmann, Wolfram; Horisberger, Roland; Ingram, Quentin; Kaestli, Hans-Christian; König, Stefan; Kotlinski, Danek; Langenegger, Urs; Renker, Dieter; Rohe, Tilman; Bachmair, Felix; Bäni, Lukas; Bianchini, Lorenzo; Bortignon, Pierluigi; Buchmann, Marco-Andrea; Casal, Bruno; Chanon, Nicolas; Deisher, Amanda; Dissertori, Günther; Dittmar, Michael; Donegà, Mauro; Dünser, Marc; Eller, Philipp; Grab, Christoph; Hits, Dmitry; Lustermann, Werner; Mangano, Boris; Marini, Andrea Carlo; Martinez Ruiz del Arbol, Pablo; Meister, Daniel; Mohr, Niklas; Nägeli, Christoph; Nef, Pascal; Nessi-Tedaldi, Francesca; Pandolfi, Francesco; Pape, Luc; Pauss, Felicitas; Peruzzi, Marco; Quittnat, Milena; Ronga, Frederic Jean; Rossini, Marco; Starodumov, Andrei; Takahashi, Maiko; Tauscher, Ludwig; Theofilatos, Konstantinos; Treille, Daniel; Wallny, Rainer; Weber, Hannsjoerg Artur; Amsler, Claude; Chiochia, Vincenzo; De Cosa, Annapaola; Favaro, Carlotta; Hinzmann, Andreas; Hreus, Tomas; Ivova Rikova, Mirena; Kilminster, Benjamin; Millan Mejias, Barbara; Ngadiuba, Jennifer; Robmann, Peter; Snoek, Hella; Taroni, Silvia; Verzetti, Mauro; Yang, Yong; Cardaci, Marco; Chen, Kuan-Hsin; Ferro, Cristina; Kuo, Chia-Ming; Li, Syue-Wei; Lin, Willis; Lu, Yun-Ju; Volpe, Roberta; Yu, Shin-Shan; Bartalini, Paolo; Chang, Paoti; Chang, You-Hao; Chang, Yu-Wei; Chao, Yuan; Chen, Kai-Feng; Chen, Po-Hsun; Dietz, Charles; Grundler, Ulysses; Hou, George Wei-Shu; Hsiung, Yee; Kao, Kai-Yi; Lei, Yeong-Jyi; Liu, Yueh-Feng; Lu, Rong-Shyang; Majumder, Devdatta; Petrakou, Eleni; Shi, Xin; Shiu, Jing-Ge; Tzeng, Yeng-Ming; Wang, Minzu; Wilken, Rachel; Asavapibhop, Burin; Suwonjandee, Narumon; Adiguzel, Aytul; Bakirci, Mustafa Numan; Cerci, Salim; Dozen, Candan; Dumanoglu, Isa; Eskut, Eda; Girgis, Semiray; Gokbulut, Gul; Gurpinar, Emine; Hos, Ilknur; Kangal, Evrim Ersin; Kayis Topaksu, Aysel; Onengut, Gulsen; Ozdemir, Kadri; Ozturk, Sertac; Polatoz, Ayse; Sogut, Kenan; Sunar Cerci, Deniz; Tali, Bayram; Topakli, Huseyin; Vergili, Mehmet; Akin, Ilina Vasileva; Aliev, Takhmasib; Bilin, Bugra; Bilmis, Selcuk; Deniz, Muhammed; Gamsizkan, Halil; Guler, Ali Murat; Karapinar, Guler; Ocalan, Kadir; Ozpineci, Altug; Serin, Meltem; Sever, Ramazan; Surat, Ugur Emrah; Yalvac, Metin; Zeyrek, Mehmet; Gülmez, Erhan; Isildak, Bora; Kaya, Mithat; Kaya, Ozlem; Ozkorucuklu, Suat; Bahtiyar, Hüseyin; Barlas, Esra; Cankocak, Kerem; Günaydin, Yusuf Oguzhan; Vardarli, Fuat Ilkehan; Yücel, Mete; Levchuk, Leonid; Sorokin, Pavel; Brooke, James John; Clement, Emyr; Cussans, David; Flacher, Henning; Frazier, Robert; Goldstein, Joel; Grimes, Mark; Heath, Greg P; Heath, Helen F; Jacob, Jeson; Kreczko, Lukasz; Lucas, Chris; Meng, Zhaoxia; Newbold, Dave M; Paramesvaran, Sudarshan; Poll, Anthony; Senkin, Sergey; Smith, Vincent J; Williams, Thomas; Bell, Ken W; Belyaev, Alexander; Brew, Christopher; Brown, Robert M; Cockerill, David JA; Coughlan, John A; Harder, Kristian; Harper, Sam; Ilic, Jelena; Olaiya, Emmanuel; Petyt, David; Shepherd-Themistocleous, Claire; Thea, Alessandro; Tomalin, Ian R; Womersley, William John; Worm, Steven; Baber, Mark; Bainbridge, Robert; Buchmuller, Oliver; Burton, Darren; Colling, David; Cripps, Nicholas; Cutajar, Michael; Dauncey, Paul; Davies, Gavin; Della Negra, Michel; Ferguson, William; Fulcher, Jonathan; Futyan, David; Gilbert, Andrew; Guneratne Bryer, Arlo; Hall, Geoffrey; Hatherell, Zoe; Hays, Jonathan; Iles, Gregory; Jarvis, Martyn; Karapostoli, Georgia; Kenzie, Matthew; Lane, Rebecca; Lucas, Robyn; Lyons, Louis; Magnan, Anne-Marie; Marrouche, Jad; Mathias, Bryn; Nandi, Robin; Nash, Jordan; Nikitenko, Alexander; Pela, Joao; Pesaresi, Mark; Petridis, Konstantinos; Pioppi, Michele; Raymond, David Mark; Rogerson, Samuel; Rose, Andrew; Seez, Christopher; Sharp, Peter; Sparrow, Alex; Tapper, Alexander; Vazquez Acosta, Monica; Virdee, Tejinder; Wakefield, Stuart; Wardle, Nicholas; Cole, Joanne; Hobson, Peter R; Khan, Akram; Kyberd, Paul; Leggat, Duncan; Leslie, Dawn; Martin, William; Reid, Ivan; Symonds, Philip; Teodorescu, Liliana; Turner, Mark; Dittmann, Jay; Hatakeyama, Kenichi; Kasmi, Azeddine; Liu, Hongxuan; Scarborough, Tara; Charaf, Otman; Cooper, Seth; Henderson, Conor; Rumerio, Paolo; Avetisyan, Aram; Bose, Tulika; Fantasia, Cory; Heister, Arno; Lawson, Philip; Lazic, Dragoslav; Rohlf, James; Sperka, David; St John, Jason; Sulak, Lawrence; Alimena, Juliette; Bhattacharya, Saptaparna; Christopher, Grant; Cutts, David; Demiragli, Zeynep; Ferapontov, Alexey; Garabedian, Alex; Heintz, Ulrich; Jabeen, Shabnam; Kukartsev, Gennadiy; Laird, Edward; Landsberg, Greg; Luk, Michael; Narain, Meenakshi; Segala, Michael; Sinthuprasith, Tutanon; Speer, Thomas; Swanson, Joshua; Breedon, Richard; Breto, Guillermo; Calderon De La Barca Sanchez, Manuel; Chauhan, Sushil; Chertok, Maxwell; Conway, John; Conway, Rylan; Cox, Peter Timothy; Erbacher, Robin; Gardner, Michael; Ko, Winston; Kopecky, Alexandra; Lander, Richard; Miceli, Tia; Pellett, Dave; Pilot, Justin; Ricci-Tam, Francesca; Rutherford, Britney; Searle, Matthew; Shalhout, Shalhout; Smith, John; Squires, Michael; Tripathi, Mani; Wilbur, Scott; Yohay, Rachel; Andreev, Valeri; Cline, David; Cousins, Robert; Erhan, Samim; Everaerts, Pieter; Farrell, Chris; Felcini, Marta; Hauser, Jay; Ignatenko, Mikhail; Jarvis, Chad; Rakness, Gregory; Schlein, Peter; Takasugi, Eric; Valuev, Vyacheslav; Weber, Matthias; Babb, John; Clare, Robert; Ellison, John Anthony; Gary, J William; Hanson, Gail; Heilman, Jesse; Jandir, Pawandeep; Lacroix, Florent; Liu, Hongliang; Long, Owen Rosser; Luthra, Arun; Malberti, Martina; Nguyen, Harold; Shrinivas, Amithabh; Sturdy, Jared; Sumowidagdo, Suharyo; Wimpenny, Stephen; Andrews, Warren; Branson, James G; Cerati, Giuseppe Benedetto; Cittolin, Sergio; D'Agnolo, Raffaele Tito; Evans, David; Holzner, André; Kelley, Ryan; Kovalskyi, Dmytro; Lebourgeois, Matthew; Letts, James; Macneill, Ian; Padhi, Sanjay; Palmer, Christopher; Pieri, Marco; Sani, Matteo; Sharma, Vivek; Simon, Sean; Sudano, Elizabeth; Tadel, Matevz; Tu, Yanjun; Vartak, Adish; Wasserbaech, Steven; Würthwein, Frank; Yagil, Avraham; Yoo, Jaehyeok; Barge, Derek; Campagnari, Claudio; Danielson, Thomas; Flowers, Kristen; Geffert, Paul; George, Christopher; Golf, Frank; Incandela, Joe; Justus, Christopher; Magaña Villalba, Ricardo; Mccoll, Nickolas; Pavlunin, Viktor; Richman, Jeffrey; Rossin, Roberto; Stuart, David; To, Wing; West, Christopher; Apresyan, Artur; Bornheim, Adolf; Bunn, Julian; Chen, Yi; Di Marco, Emanuele; Duarte, Javier; Kcira, Dorian; Mott, Alexander; Newman, Harvey B; Pena, Cristian; Rogan, Christopher; Spiropulu, Maria; Timciuc, Vladlen; Wilkinson, Richard; Xie, Si; Zhu, Ren-Yuan; Azzolini, Virginia; Calamba, Aristotle; Carroll, Ryan; Ferguson, Thomas; Iiyama, Yutaro; Jang, Dong Wook; Paulini, Manfred; Russ, James; Vogel, Helmut; Vorobiev, Igor; Cumalat, John Perry; Drell, Brian Robert; Ford, William T; Gaz, Alessandro; Luiggi Lopez, Eduardo; Nauenberg, Uriel; Smith, James; Stenson, Kevin; Ulmer, Keith; Wagner, Stephen Robert; Alexander, James; Chatterjee, Avishek; Eggert, Nicholas; Gibbons, Lawrence Kent; Hopkins, Walter; Khukhunaishvili, Aleko; Kreis, Benjamin; Mirman, Nathan; Nicolas Kaufman, Gala; Patterson, Juliet Ritchie; Ryd, Anders; Salvati, Emmanuele; Sun, Werner; Teo, Wee Don; Thom, Julia; Thompson, Joshua; Tucker, Jordan; Weng, Yao; Winstrom, Lucas; Wittich, Peter; Winn, Dave; Abdullin, Salavat; Albrow, Michael; Anderson, Jacob; Apollinari, Giorgio; Bauerdick, Lothar AT; Beretvas, Andrew; Berryhill, Jeffrey; Bhat, Pushpalatha C; Burkett, Kevin; Butler, Joel Nathan; Chetluru, Vasundhara; Cheung, Harry; Chlebana, Frank; Cihangir, Selcuk; Elvira, Victor Daniel; Fisk, Ian; Freeman, Jim; Gao, Yanyan; Gottschalk, Erik; Gray, Lindsey; Green, Dan; Grünendahl, Stefan; Gutsche, Oliver; Hare, Daryl; Harris, Robert M; Hirschauer, James; Hooberman, Benjamin; Jindariani, Sergo; Johnson, Marvin; Joshi, Umesh; Kaadze, Ketino; Klima, Boaz; Kwan, Simon; Linacre, Jacob; Lincoln, Don; Lipton, Ron; Lykken, Joseph; Maeshima, Kaori; Marraffino, John Michael; Martinez Outschoorn, Verena Ingrid; Maruyama, Sho; Mason, David; McBride, Patricia; Mishra, Kalanand; Mrenna, Stephen; Musienko, Yuri; Nahn, Steve; Newman-Holmes, Catherine; O'Dell, Vivian; Prokofyev, Oleg; Ratnikova, Natalia; Sexton-Kennedy, Elizabeth; Sharma, Seema; Spalding, William J; Spiegel, Leonard; Taylor, Lucas; Tkaczyk, Slawek; Tran, Nhan Viet; Uplegger, Lorenzo; Vaandering, Eric Wayne; Vidal, Richard; Whitbeck, Andrew; Whitmore, Juliana; Wu, Weimin; Yang, Fan; Yun, Jae Chul; Acosta, Darin; Avery, Paul; Bourilkov, Dimitri; Cheng, Tongguang; Das, Souvik; De Gruttola, Michele; Di Giovanni, Gian Piero; Dobur, Didar; Field, Richard D; Fisher, Matthew; Fu, Yu; Furic, Ivan-Kresimir; Hugon, Justin; Kim, Bockjoo; Konigsberg, Jacobo; Korytov, Andrey; Kropivnitskaya, Anna; Kypreos, Theodore; Low, Jia Fu; Matchev, Konstantin; Milenovic, Predrag; Mitselmakher, Guenakh; Muniz, Lana; Rinkevicius, Aurelijus; Shchutska, Lesya; Skhirtladze, Nikoloz; Snowball, Matthew; Yelton, John; Zakaria, Mohammed; Gaultney, Vanessa; Hewamanage, Samantha; Linn, Stephan; Markowitz, Pete; Martinez, German; Rodriguez, Jorge Luis; Adams, Todd; Askew, Andrew; Bochenek, Joseph; Chen, Jie; Diamond, Brendan; Haas, Jeff; Hagopian, Sharon; Hagopian, Vasken; Johnson, Kurtis F; Prosper, Harrison; Veeraraghavan, Venkatesh; Weinberg, Marc; Baarmand, Marc M; Dorney, Brian; Hohlmann, Marcus; Kalakhety, Himali; Yumiceva, Francisco; Adams, Mark Raymond; Apanasevich, Leonard; Bazterra, Victor Eduardo; Betts, Russell Richard; Bucinskaite, Inga; Cavanaugh, Richard; Evdokimov, Olga; Gauthier, Lucie; Gerber, Cecilia Elena; Hofman, David Jonathan; Khalatyan, Samvel; Kurt, Pelin; Moon, Dong Ho; O'Brien, Christine; Silkworth, Christopher; Turner, Paul; Varelas, Nikos; Akgun, Ugur; Albayrak, Elif Asli; Bilki, Burak; Clarida, Warren; Dilsiz, Kamuran; Duru, Firdevs; Haytmyradov, Maksat; Merlo, Jean-Pierre; Mermerkaya, Hamit; Mestvirishvili, Alexi; Moeller, Anthony; Nachtman, Jane; Ogul, Hasan; Onel, Yasar; Ozok, Ferhat; Sen, Sercan; Tan, Ping; Tiras, Emrah; Wetzel, James; Yetkin, Taylan; Yi, Kai; Barnett, Bruce Arnold; Blumenfeld, Barry; Bolognesi, Sara; Fehling, David; Gritsan, Andrei; Maksimovic, Petar; Martin, Christopher; Swartz, Morris; Baringer, Philip; Bean, Alice; Benelli, Gabriele; Kenny III, Raymond Patrick; Murray, Michael; Noonan, Daniel; Sanders, Stephen; Sekaric, Jadranka; Stringer, Robert; Wang, Quan; Wood, Jeffrey Scott; Barfuss, Anne-Fleur; Chakaberia, Irakli; Ivanov, Andrew; Khalil, Sadia; Makouski, Mikhail; Maravin, Yurii; Saini, Lovedeep Kaur; Shrestha, Shruti; Svintradze, Irakli; Gronberg, Jeffrey; Lange, David; Rebassoo, Finn; Wright, Douglas; Baden, Drew; Calvert, Brian; Eno, Sarah Catherine; Gomez, Jaime; Hadley, Nicholas John; Kellogg, Richard G; Kolberg, Ted; Lu, Ying; Marionneau, Matthieu; Mignerey, Alice; Pedro, Kevin; Skuja, Andris; Temple, Jeffrey; Tonjes, Marguerite; Tonwar, Suresh C; Apyan, Aram; Barbieri, Richard; Bauer, Gerry; Busza, Wit; Cali, Ivan Amos; Chan, Matthew; Di Matteo, Leonardo; Dutta, Valentina; Gomez Ceballos, Guillelmo; Goncharov, Maxim; Gulhan, Doga; Klute, Markus; Lai, Yue Shi; Lee, Yen-Jie; Levin, Andrew; Luckey, Paul David; Ma, Teng; Paus, Christoph; Ralph, Duncan; Roland, Christof; Roland, Gunther; Stephans, George; Stöckli, Fabian; Sumorok, Konstanty; Velicanu, Dragos; Veverka, Jan; Wyslouch, Bolek; Yang, Mingming; Yoon, Sungho; Zanetti, Marco; Zhukova, Victoria; Dahmes, Bryan; De Benedetti, Abraham; Gude, Alexander; Kao, Shih-Chuan; Klapoetke, Kevin; Kubota, Yuichi; Mans, Jeremy; Pastika, Nathaniel; Rusack, Roger; Singovsky, Alexander; Tambe, Norbert; Turkewitz, Jared; Acosta, John Gabriel; Cremaldi, Lucien Marcus; Kroeger, Rob; Oliveros, Sandra; Perera, Lalith; Rahmat, Rahmat; Sanders, David A; Summers, Don; Avdeeva, Ekaterina; Bloom, Kenneth; Bose, Suvadeep; Claes, Daniel R; Dominguez, Aaron; Gonzalez Suarez, Rebeca; Keller, Jason; Knowlton, Dan; Kravchenko, Ilya; Lazo-Flores, Jose; Malik, Sudhir; Meier, Frank; Snow, Gregory R; Dolen, James; Godshalk, Andrew; Iashvili, Ia; Jain, Supriya; Kharchilava, Avto; Kumar, Ashish; Rappoccio, Salvatore; Alverson, George; Barberis, Emanuela; Baumgartel, Darin; Chasco, Matthew; Haley, Joseph; Massironi, Andrea; Nash, David; Orimoto, Toyoko; Trocino, Daniele; Wood, Darien; Zhang, Jinzhong; Anastassov, Anton; Hahn, Kristan Allan; Kubik, Andrew; Lusito, Letizia; Mucia, Nicholas; Odell, Nathaniel; Pollack, Brian; Pozdnyakov, Andrey; Schmitt, Michael Henry; Stoynev, Stoyan; Sung, Kevin; Velasco, Mayda; Won, Steven; Berry, Douglas; Brinkerhoff, Andrew; Chan, Kwok Ming; Drozdetskiy, Alexey; Hildreth, Michael; Jessop, Colin; Karmgard, Daniel John; Kellams, Nathan; Kolb, Jeff; Lannon, Kevin; Luo, Wuming; Lynch, Sean; Marinelli, Nancy; Morse, David Michael; Pearson, Tessa; Planer, Michael; Ruchti, Randy; Slaunwhite, Jason; Valls, Nil; Wayne, Mitchell; Wolf, Matthias; Woodard, Anna; Antonelli, Louis; Bylsma, Ben; Durkin, Lloyd Stanley; Flowers, Sean; Hill, Christopher; Hughes, Richard; Kotov, Khristian; Ling, Ta-Yung; Puigh, Darren; Rodenburg, Marissa; Smith, Geoffrey; Vuosalo, Carl; Winer, Brian L; Wolfe, Homer; Wulsin, Howard Wells; Berry, Edmund; Elmer, Peter; Halyo, Valerie; Hebda, Philip; Hegeman, Jeroen; Hunt, Adam; Jindal, Pratima; Koay, Sue Ann; Lujan, Paul; Marlow, Daniel; Medvedeva, Tatiana; Mooney, Michael; Olsen, James; Piroué, Pierre; Quan, Xiaohang; Raval, Amita; Saka, Halil; Stickland, David; Tully, Christopher; Werner, Jeremy Scott; Zenz, Seth Conrad; Zuranski, Andrzej; Brownson, Eric; Lopez, Angel; Mendez, Hector; Ramirez Vargas, Juan Eduardo; Alagoz, Enver; Benedetti, Daniele; Bolla, Gino; Bortoletto, Daniela; De Mattia, Marco; Everett, Adam; Hu, Zhen; Jha, Manoj; Jones, Matthew; Jung, Kurt; Kress, Matthew; Leonardo, Nuno; Lopes Pegna, David; Maroussov, Vassili; Merkel, Petra; Miller, David Harry; Neumeister, Norbert; Radburn-Smith, Benjamin Charles; Shipsey, Ian; Silvers, David; Svyatkovskiy, Alexey; Wang, Fuqiang; Xie, Wei; Xu, Lingshan; Yoo, Hwi Dong; Zablocki, Jakub; Zheng, Yu; Parashar, Neeti; Adair, Antony; Akgun, Bora; Ecklund, Karl Matthew; Geurts, Frank JM; Li, Wei; Michlin, Benjamin; Padley, Brian Paul; Redjimi, Radia; Roberts, Jay; Zabel, James; Betchart, Burton; Bodek, Arie; Covarelli, Roberto; de Barbaro, Pawel; Demina, Regina; Eshaq, Yossof; Ferbel, Thomas; Garcia-Bellido, Aran; Goldenzweig, Pablo; Han, Jiyeon; Harel, Amnon; Miner, Daniel Carl; Petrillo, Gianluca; Vishnevskiy, Dmitry; Zielinski, Marek; Bhatti, Anwar; Ciesielski, Robert; Demortier, Luc; Goulianos, Konstantin; Lungu, Gheorghe; Malik, Sarah; Mesropian, Christina; Arora, Sanjay; Barker, Anthony; Chou, John Paul; Contreras-Campana, Christian; Contreras-Campana, Emmanuel; Duggan, Daniel; Ferencek, Dinko; Gershtein, Yuri; Gray, Richard; Halkiadakis, Eva; Hidas, Dean; Lath, Amitabh; Panwalkar, Shruti; Park, Michael; Patel, Rishi; Rekovic, Vladimir; Robles, Jorge; Salur, Sevil; Schnetzer, Steve; Seitz, Claudia; Somalwar, Sunil; Stone, Robert; Thomas, Scott; Thomassen, Peter; Walker, Matthew; Rose, Keith; Spanier, Stefan; Yang, Zong-Chang; York, Andrew; Bouhali, Othmane; Eusebi, Ricardo; Flanagan, Will; Gilmore, Jason; Kamon, Teruki; Khotilovich, Vadim; Krutelyov, Vyacheslav; Montalvo, Roy; Osipenkov, Ilya; Pakhotin, Yuriy; Perloff, Alexx; Roe, Jeffrey; Safonov, Alexei; Sakuma, Tai; Suarez, Indara; Tatarinov, Aysen; Toback, David; Akchurin, Nural; Cowden, Christopher; Damgov, Jordan; Dragoiu, Cosmin; Dudero, Phillip Russell; Kovitanggoon, Kittikul; Kunori, Shuichi; Lee, Sung Won; Libeiro, Terence; Volobouev, Igor; Appelt, Eric; Delannoy, Andrés G; Greene, Senta; Gurrola, Alfredo; Johns, Willard; Maguire, Charles; Mao, Yaxian; Melo, Andrew; Sharma, Monika; Sheldon, Paul; Snook, Benjamin; Tuo, Shengquan; Velkovska, Julia; Arenton, Michael Wayne; Boutle, Sarah; Cox, Bradley; Francis, Brian; Goodell, Joseph; Hirosky, Robert; Ledovskoy, Alexander; Lin, Chuanzhe; Neu, Christopher; Wood, John; Gollapinni, Sowjanya; Harr, Robert; Karchin, Paul Edmund; Kottachchi Kankanamge Don, Chamath; Lamichhane, Pramod; Belknap, Donald; Borrello, Laura; Carlsmith, Duncan; Cepeda, Maria; Dasu, Sridhara; Duric, Senka; Friis, Evan; Grothe, Monika; Hall-Wilton, Richard; Herndon, Matthew; Hervé, Alain; Klabbers, Pamela; Klukas, Jeffrey; Lanaro, Armando; Levine, Aaron; Loveless, Richard; Mohapatra, Ajit; Ojalvo, Isabel; Perry, Thomas; Pierro, Giuseppe Antonio; Polese, Giovanni; Ross, Ian; Sakharov, Alexandre; Sarangi, Tapas; Savin, Alexander; Smith, Wesley H

    2014-10-16

    Measurements of the inclusive jet cross section with the anti-$k_t$ clustering algorithm are presented for two radius parameters, R=0.5 and 0.7. They are based on data from LHC proton-proton collisions at $\\sqrt{s}$ = 7 TeV corresponding to an integrated luminosity of 5.0 inverse-femtobarns collected with the CMS detector in 2011. The ratio of these two measurements is obtained as a function of the rapidity and transverse momentum of the jets. Significant discrepancies are found comparing the data to leading-order simulations and to fixed-order calculations at next-to-leading order, corrected for nonperturbative effects, whereas simulations with next-to-leading-order matrix elements matched to parton showers describe the data best.

  12. Concurrent magnetic and structural reconstructions at the interface of (111)-oriented L a0.7S r0.3Mn O3/LaFe O3

    Science.gov (United States)

    Hallsteinsen, I.; Moreau, M.; Grutter, A.; Nord, M.; Vullum, P.-E.; Gilbert, D. A.; Bolstad, T.; Grepstad, J. K.; Holmestad, R.; Selbach, S. M.; N'Diaye, A. T.; Kirby, B. J.; Arenholz, E.; Tybell, T.

    2016-11-01

    We observe an induced switchable magnetic moment of 1.6 ±0.40 μB/Fe for the nominally antiferromagnetic LaFe O3 extending two to four interface layers into the non-charge transfer system L a0.7S r0.3Mn O3/LaFe O3/SrTi O3(111 ) . Simultaneously a mismatch of oxygen octahedra rotations at the interface implies an atomic reconstruction of reduced symmetry at the interface, reaching two to five layers into LaFe O3 . Density functional theory of a structure with atomic reconstruction and different correlation strength shows a ferrimagnetic state with a net Fe moment at the interface. Together these results suggest that engineered oxygen octahedra rotations, affecting the local symmetry, affect electron correlations and can be used to promote magnetic properties.

  13. Measurement of the ratio of inclusive jet cross sections using the anti-kt algorithm with radius parameters R = 0.5 and 0.7 in pp collisions at sqrt(s) = 7 TeV

    Energy Technology Data Exchange (ETDEWEB)

    Chatrchyan, Serguei [Yerevan Physics Institute (Armenia); et al.,

    2014-10-01

    Measurements of the inclusive jet cross section with the anti-kt clustering algorithm are presented for two radius parameters, R=0.5 and 0.7. They are based on data from LHC proton-proton collisions at $\\sqrt{s}$ = 7 TeV corresponding to an integrated luminosity of 5.0 inverse femtobarns collected with the CMS detector in 2011. The ratio of these two measurements is obtained as a function of the rapidity and transverse momentum of the jets. Significant discrepancies are found comparing the data to leading-order simulations and to fixed-order calculations at next-to-leading order, corrected for nonperturbative effects, whereas simulations with next-to-leading-order matrix elements matched to parton showers describe the data best.

  14. A conformal block Farey tail

    CERN Document Server

    Maloney, Alexander; Ng, Gim Seng

    2016-01-01

    We investigate the constraints of crossing symmetry on CFT correlation functions. Four point conformal blocks are naturally viewed as functions on the upper-half plane, on which crossing symmetry acts by PSL(2,Z) modular transformations. This allows us to construct a unique, crossing symmetric function out of a given conformal block by averaging over PSL(2,Z). In some two dimensional CFTs the correlation functions are precisely equal to the modular average of the contributions of a finite number of light states. For example, in the two dimensional Ising and tri-critical Ising model CFTs, the correlation functions of identical operators are equal to the PSL(2,Z) average of the Virasoro vacuum block; this determines the 3 point function coefficients uniquely in terms of the central charge. The sum over PSL(2,Z) in CFT2 has a natural AdS3 interpretation as a sum over semi-classical saddle points, which describe particles propagating along rational tangles in the bulk. We demonstrate this explicitly for the corre...

  15. Holography and Conformal Anomaly Matching

    CERN Document Server

    Cabo-Bizet, Alejandro; Narain, K S

    2013-01-01

    We discuss various issues related to the understanding of the conformal anomaly matching in CFT from the dual holographic viewpoint. First, we act with a PBH diffeomorphism on a generic 5D RG flow geometry and show that the corresponding on-shell bulk action reproduces the Wess-Zumino term for the dilaton of broken conformal symmetry, with the expected coefficient aUV-aIR. Then we consider a specific 3D example of RG flow whose UV asymptotics is normalizable and admits a 6D lifting. We promote a modulus \\rho appearing in the geometry to a function of boundary coordinates. In a 6D description {\\rho} is the scale of an SU(2) instanton. We determine the smooth deformed background up to second order in the space-time derivatives of \\rho and find that the 3D on-shell action reproduces a boundary kinetic term for the massless field \\tau= log(\\rho) with the correct coefficient \\delta c=cUV-cIR. We further analyze the linearized fluctuations around the deformed background geometry and compute the one-point functions ...

  16. Conformational effects on hydrazine and OH coadsorption on Ni(111): A first-principles investigation

    Science.gov (United States)

    Agusta, Mohammad Kemal; Purwoko, Prasetiyo Hadi; Saputro, Adhitya Gandaryus; Fathurrahman, Fadjar; Dipojono, Hermawan K.; Diño, Wilson Agerico

    2017-10-01

    Using first-principles Density Functional Theory calculations, we investigated coadsorption of hydrazine (N2H4) and OH on Ni(111) surface. Two types of N2H4 conformations: anti and cis-conformer, with coadsorbed OH on several high symmetry sites on Ni(111) surface were studied. We found that coadsorption with cis-conformer N2H4 significantly modifies OH site preferences while such modification is less profound for coadsorption with anti-conformer N2H4. On the other way around, the cis-confomer N2H4 coadsorption becomes more stable due to the pressence of OH. We identified the electrostatic attractive dipole interaction between the coadsorbed species as the underlying mechanism for the stabilization. This electrostatic interaction is particularly strong for cis-conformer N2H4 due to its large dipole moment. We also found Nsbnd H bond elongation for cis-conformer N2H4 coadsorption with OH due to the interaction between accumulated charge in OH with the H atom of N2H4. Therefore, it can be inferred that coadsorption with OH promotes the dehydrogenation reaction of N2H4 via stabilization of cis-confomer N2H4.

  17. Two Na+ Sites Control Conformational Change in a Neurotransmitter Transporter Homolog.

    Science.gov (United States)

    Tavoulari, Sotiria; Margheritis, Eleonora; Nagarajan, Anu; DeWitt, David C; Zhang, Yuan-Wei; Rosado, Edwin; Ravera, Silvia; Rhoades, Elizabeth; Forrest, Lucy R; Rudnick, Gary

    2016-01-15

    In LeuT, a prokaryotic homolog of neurotransmitter transporters, Na(+) stabilizes outward-open conformational states. We examined how each of the two LeuT Na(+) binding sites contributes to Na(+)-dependent closure of the cytoplasmic pathway using biochemical and biophysical assays of conformation. Mutating either of two residues that contribute to the Na2 site completely prevented cytoplasmic closure in response to Na(+), suggesting that Na2 is essential for this conformational change, whereas Na1 mutants retained Na(+) responsiveness. However, mutation of Na1 residues also influenced the Na(+)-dependent conformational change in ways that varied depending on the position mutated. Computational analyses suggest those mutants influence the ability of Na1 binding to hydrate the substrate pathway and perturb an interaction network leading to the extracellular gate. Overall, the results demonstrate that occupation of Na2 stabilizes outward-facing conformations presumably through a direct interaction between Na(+) and transmembrane helices 1 and 8, whereas Na(+) binding at Na1 influences conformational change through a network of intermediary interactions. The results also provide evidence that N-terminal release and helix motions represent distinct steps in cytoplasmic pathway opening.

  18. Two Na+ Sites Control Conformational Change in a Neurotransmitter Transporter Homolog*

    Science.gov (United States)

    Tavoulari, Sotiria; Margheritis, Eleonora; Nagarajan, Anu; DeWitt, David C.; Zhang, Yuan-Wei; Rosado, Edwin; Ravera, Silvia; Rhoades, Elizabeth; Forrest, Lucy R.; Rudnick, Gary

    2016-01-01

    In LeuT, a prokaryotic homolog of neurotransmitter transporters, Na+ stabilizes outward-open conformational states. We examined how each of the two LeuT Na+ binding sites contributes to Na+-dependent closure of the cytoplasmic pathway using biochemical and biophysical assays of conformation. Mutating either of two residues that contribute to the Na2 site completely prevented cytoplasmic closure in response to Na+, suggesting that Na2 is essential for this conformational change, whereas Na1 mutants retained Na+ responsiveness. However, mutation of Na1 residues also influenced the Na+-dependent conformational change in ways that varied depending on the position mutated. Computational analyses suggest those mutants influence the ability of Na1 binding to hydrate the substrate pathway and perturb an interaction network leading to the extracellular gate. Overall, the results demonstrate that occupation of Na2 stabilizes outward-facing conformations presumably through a direct interaction between Na+ and transmembrane helices 1 and 8, whereas Na+ binding at Na1 influences conformational change through a network of intermediary interactions. The results also provide evidence that N-terminal release and helix motions represent distinct steps in cytoplasmic pathway opening. PMID:26582198

  19. Study on Mechanism of Rare Earth PVC Stabilizer

    Institute of Scientific and Technical Information of China (English)

    彭振博; 胡斌; 苏庆德; 曲锦忠

    2003-01-01

    Rare earth compounds can be used as PVC thermal stabilizers. According to the infrared spectra of the mixture of PVC and some stearates, the mechanism of stabilization of different stearates was studied. The specialty of rare earth stabilizers was found. They can change the conformation of PVC and restrain the elimination of HCl. From this aspect, the unique synergetic effect with other stabilizers of rare earth compounds can be explained.

  20. Fluorine Substitution in Neurotransmitters: Microwave Spectroscopy and Modelling of the Conformational Space and Non Bonding Interactions

    Science.gov (United States)

    Melandri, S.; Maris, A.; Merloni, A.

    2011-06-01

    Fluorine substitution in molecules is a common practice in bio-organic chemistry in order to modulate physicochemical properties and biological activity of molecules and an increasing number of drugs on the market contain fluorine, the presence of which is often of major importance to modify pharmacokinetics properties and molecular activity. The rationale for such a strategy is that fluorine is generally a stronger electron acceptor than the other halogen atoms and its size is intermediate between that of hydrogen and oxygen. We have studied two fluorinated analogs of 2-phenylethylamine (PEA), the prototype molecule for adrenergic neurotransmitters, namely: 4-Fluoro (4FPEA) and 2-Fluoro-2-phenylethylamine (2FPEA) by Molecular Beam Fourier Transform Microwave Spectroscopy in the frequency range 6-18 GHz and ab initio calculations at the MP2/6311++G** level. The aim is to obtain information on the spatial arrangement of the ethylamine side chain and the effects of fluorination on the energy landscape. The conformational space is dominated by low energy gauche conformations stabilized by weak interactions between the aminic hydrogens and the electron cloud of the benzene ring and anti conformations higher in energy. In 2FPEA the presence of the fluorine atom almost duplicate the number of possible conformation with respect to 4FPEA. We observed two conformers of 4FPEA and five conformers of 2FPEA which have been classified with the guide provided by accurate ab initio calculations. The identification of the conformational species was helped by the analysis of the quadrupole hyperfine pattern which is greatly influenced by the orientation of the amino group and acts as a fingerprint for each conformation. The orientation of the dipole moment within the principal axis frame and the order of stability of the different conformations are other independent pieces of evidence for the unambiguous assignment and identification of the conformers. The order of stability was

  1. Axial symmetry and conformal Killing vectors

    CERN Document Server

    Mars, M; Mars, Marc; Senovilla, Jose M.M.

    1993-01-01

    Axisymmetric spacetimes with a conformal symmetry are studied and it is shown that, if there is no further conformal symmetry, the axial Killing vector and the conformal Killing vector must commute. As a direct consequence, in conformally stationary and axisymmetric spacetimes, no restriction is made by assuming that the axial symmetry and the conformal timelike symmetry commute. Furthermore, we prove that in axisymmetric spacetimes with another symmetry (such as stationary and axisymmetric or cylindrically symmetric spacetimes) and a conformal symmetry, the commutator of the axial Killing vector with the two others mush vanish or else the symmetry is larger than that originally considered. The results are completely general and do not depend on Einstein's equations or any particular matter content.

  2. Simulating Protein Conformations through Global Optimization

    CERN Document Server

    Mucherino, A; Pardalos, P M

    2008-01-01

    Many researches have been working on the protein folding problem from more than half century. Protein folding is indeed one of the major unsolved problems in science. In this work, we discuss a model for the simulation of protein conformations. This simple model is based on the idea of imposing few geometric requirements on chains of atoms representing the backbone of a protein conformation. The model leads to the formulation of a global optimization problem, whose solutions correspond to conformations satisfying the desired requirements. The global optimization problem is solved by the recently proposed Monkey Search algorithm. The simplicity of the optimization problem and the effectiveness of the used meta-heuristic search allowed the simulation of a large set of high-quality conformations. We show that, even though only few geometric requirements are imposed, some of the simulated conformation results to be similar (in terms of RMSD) to conformations real proteins actually have in nature.

  3. 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.

  4. Conformal submanifold geometry I-III

    CERN Document Server

    Burstall, Francis E

    2010-01-01

    In Part I, we develop the notions of a Moebius structure and a conformal Cartan geometry, establish an equivalence between them; we use them in Part II to study submanifolds of conformal manifolds in arbitrary dimension and codimension. We obtain Gauss-Codazzi-Ricci equations and a conformal Bonnet theorem characterizing immersed submanifolds of the conformal n-sphere. These methods are applied in Part III to study constrained Willmore surfaces, isothermic surfaces, Guichard surfaces and conformally-flat submanifolds with flat normal bundle, and their spectral deformations, in arbitrary codimension. The high point of these applications is a unified theory of Moebius-flat submanifolds, which include Guichard surfaces and conformally flat hypersurfaces.

  5. Conformal symmetries of FRW accelerating cosmologies

    Energy Technology Data Exchange (ETDEWEB)

    Kehagias, A. [Physics Division, National Technical University of Athens, 15780 Zografou Campus, Athens (Greece); Department of Theoretical Physics and Center for Astroparticle Physics (CAP) 24 quai E. Ansermet, CH-1211 Geneva 4 (Switzerland); Riotto, A. [Department of Theoretical Physics and Center for Astroparticle Physics (CAP) 24 quai E. Ansermet, CH-1211 Geneva 4 (Switzerland)

    2014-07-15

    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.

  6. The C–F bond as a conformational tool in organic and biological chemistry

    Directory of Open Access Journals (Sweden)

    Luke Hunter

    2010-04-01

    Full Text Available Organofluorine compounds are widely used in many different applications, ranging from pharmaceuticals and agrochemicals to advanced materials and polymers. It has been recognised for many years that fluorine substitution can confer useful molecular properties such as enhanced stability and hydrophobicity. Another impact of fluorine substitution is to influence the conformations of organic molecules. The stereoselective introduction of fluorine atoms can therefore be exploited as a conformational tool for the synthesis of shape-controlled functional molecules. This review will begin by describing some general aspects of the C–F bond and the various conformational effects associated with C–F bonds (i.e. dipole–dipole interactions, charge–dipole interactions and hyperconjugation. Examples of functional molecules that exploit these conformational effects will then be presented, drawing from a diverse range of molecules including pharmaceuticals, organocatalysts, liquid crystals and peptides.

  7. Conformational Heterogeneity of Bax Helix 9 Dimer for Apoptotic Pore Formation

    Science.gov (United States)

    Liao, Chenyi; Zhang, Zhi; Kale, Justin; Andrews, David W.; Lin, Jialing; Li, Jianing

    2016-07-01

    Helix α9 of Bax protein can dimerize in the mitochondrial outer membrane (MOM) and lead to apoptotic pores. However, it remains unclear how different conformations of the dimer contribute to the pore formation on the molecular level. Thus we have investigated various conformational states of the α9 dimer in a MOM model — using computer simulations supplemented with site-specific mutagenesis and crosslinking of the α9 helices. Our data not only confirmed the critical membrane environment for the α9 stability and dimerization, but also revealed the distinct lipid-binding preference of the dimer in different conformational states. In our proposed pathway, a crucial iso-parallel dimer that mediates the conformational transition was discovered computationally and validated experimentally. The corroborating evidence from simulations and experiments suggests that, helix α9 assists Bax activation via the dimer heterogeneity and interactions with specific MOM lipids, which eventually facilitate proteolipidic pore formation in apoptosis regulation.

  8. Conformal doping of topographic silicon structures using a radial line slot antenna plasma source

    Science.gov (United States)

    Ueda, Hirokazu; Ventzek, Peter L. G.; Oka, Masahiro; Horigome, Masahiro; Kobayashi, Yuuki; Sugimoto, Yasuhiro; Nozawa, Toshihisa; Kawakami, Satoru

    2014-06-01

    Fin extension doping for 10 nm front end of line technology requires ultra-shallow high dose conformal doping. In this paper, we demonstrate a new radial line slot antenna plasma source based doping process that meets these requirements. Critical to reaching true conformality while maintaining fin integrity is that the ion energy be low and controllable, while the dose absorption is self-limited. The saturated dopant later is rendered conformal by concurrent amorphization and dopant containing capping layer deposition followed by stabilization anneal. Dopant segregation assists in driving dopants from the capping layer into the sub silicon surface. Very high resolution transmission electron microscopy-Energy Dispersive X-ray spectroscopy, used to prove true conformality, was achieved. We demonstrate these results using an n-type arsenic based plasma doping process on 10 to 40 nm high aspect ratio fins structures. The results are discussed in terms of the different types of clusters that form during the plasma doping process.

  9. The C–F bond as a conformational tool in organic and biological chemistry

    Science.gov (United States)

    2010-01-01

    Summary Organofluorine compounds are widely used in many different applications, ranging from pharmaceuticals and agrochemicals to advanced materials and polymers. It has been recognised for many years that fluorine substitution can confer useful molecular properties such as enhanced stability and hydrophobicity. Another impact of fluorine substitution is to influence the conformations of organic molecules. The stereoselective introduction of fluorine atoms can therefore be exploited as a conformational tool for the synthesis of shape-controlled functional molecules. This review will begin by describing some general aspects of the C–F bond and the various conformational effects associated with C–F bonds (i.e. dipole–dipole interactions, charge–dipole interactions and hyperconjugation). Examples of functional molecules that exploit these conformational effects will then be presented, drawing from a diverse range of molecules including pharmaceuticals, organocatalysts, liquid crystals and peptides. PMID:20502650

  10. Spectroscopy Investigation on Conformational Transition of Tea Glycoconjugate from Green Tea

    Institute of Scientific and Technical Information of China (English)

    CHEN,Hai-Xia(陈海霞); ZHANG,Min(张民); XIE,Bi-Jun(谢笔钧)

    2004-01-01

    The conformational transition of a new glycoconjugate,tea glycoconjugate(TGC),was investigated by spectroscopy techniques including circular dichroism(CD)and ultraviolet(UV)spectroscopy.The solution behaviors of TGC inthe mediums of different temperature,pH value,and ions were compared.Results showed that the native conformation of TGC was partially ordered.The CD value and UV absorbance of TGC altered with the change of pH value,temperature,the addition of ions,and also accompanied order-disorder transition.Especially the conditions with temperature higher than the glasstransition temperature(Tg=62℃),higher pH value orlower pH value will have the most impact on the conformation of TGC,which will destroy the hydrogen bonds between the TGC molecules.The results indicated that the outside factors playimportant roles onthe stability of the conformation of TGC.

  11. Natively unfolded human prothymosin alpha adopts partially folded collapsed conformation at acidic pH.

    Science.gov (United States)

    Uversky, V N; Gillespie, J R; Millett, I S; Khodyakova, A V; Vasiliev, A M; Chernovskaya, T V; Vasilenko, R N; Kozlovskaya, G D; Dolgikh, D A; Fink, A L; Doniach, S; Abramov, V M

    1999-11-09

    Prothymosin alpha has previously been shown to be unfolded at neutral pH, thus belonging to a growing family of "natively unfolded" proteins. The structural properties and conformational stability of recombinant human prothymosin alpha were characterized at neutral and acidic pH by gel filtration, SAXS, circular dichroism, ANS fluorescence, (1)H NMR, and resistance to urea-induced unfolding. Interestingly, prothymosin alpha underwent a cooperative transition from the unfolded state into a partially folded conformation on lowering the pH. This conformation of prothymosin alpha is a compact denatured state, with structural properties different from those of the molten globule. The formation of alpha-helical structure by the glutamic acid-rich elements of the protein accompanied by the partial hydrophobic collapse is expected at lower pH due to the neutralization of the negatively charged residues. It is possible that such conformational changes may be associated with the protein function.

  12. TASI Lectures on the Conformal Bootstrap

    CERN Document Server

    Simmons-Duffin, David

    2016-01-01

    These notes are from courses given at TASI and the Advanced Strings School in summer 2015. Starting from principles of quantum field theory and the assumption of a traceless stress tensor, we develop the basics of conformal field theory, including conformal Ward identities, radial quantization, reflection positivity, the operator product expansion, and conformal blocks. We end with an introduction to numerical bootstrap methods, focusing on the 2d and 3d Ising models.

  13. Conformal Invariance and Quantum Nature of Particles

    CERN Document Server

    Salehi, H; Salehi, Hadi; Bisabr, Yousef

    2003-01-01

    We investigate a gravitational model whose vacuum sector is invariant under conformal transformations. In this model, matter is taken to be coupled with a metric which is different but conformally related to the metric appearing explicitly in the vacuum sector. It is then show that the effect of a conformal symmetry breaking would lead to a particle concept. In particular, a correspondence between quantum nature of the particles and the gravitational interaction of matter is established.

  14. Multiple conformations of proteins in native state

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Examples of protein sequences that can adopt multiple native states are recently accumulated. Characterization of the protein multiple conformations will have important implications for our understanding of the relationship between structure and function, and their folding kinetics. In present review, the experimental evidence for the existence of multiple conformations in the native state of proteins, the molecular basis and the biological significance of multiple conformations of proteins are focused.

  15. 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....

  16. Opening the conformation is a master switch for the dual localization and phosphatase activity of PTEN

    Science.gov (United States)

    Nguyen, Hoai-Nghia; Yang, Jr-Ming; Miyamoto, Takafumi; Itoh, Kie; Rho, Elmer; Zhang, Qiang; Inoue, Takanari; Devreotes, Peter N.; Sesaki, Hiromi; Iijima, Miho

    2015-01-01

    Tumor suppressor PTEN mainly functions at two subcellular locations, the plasma membrane and the nucleus. At the plasma membrane, PTEN dephosphorylates the tumorigenic second messenger PIP3, which drives cell proliferation and migration. In the nucleus, PTEN controls DNA repair and genome stability independently of PIP3. Whereas the concept that a conformational change regulates protein function through post-translational modifications has been well established in biology, it is unknown whether a conformational change simultaneously controls dual subcellular localizations of proteins. Here, we discovered that opening the conformation of PTEN is the crucial upstream event that determines its key dual localizations of this crucial tumor suppressor. We identify a critical conformational switch that regulates PTEN’s localization. Most PTEN molecules are held in the cytosol in a closed conformation by intramolecular interactions between the C-terminal tail and core region. Dephosphorylation of the tail opens the conformation and exposes the membrane-binding regulatory interface in the core region, recruiting PTEN to the membrane. Moreover, a lysine at residue 13 is also exposed and when ubiquitinated, transports PTEN to the nucleus. Thus, opening the conformation of PTEN is a key mechanism that enhances its dual localization and enzymatic activity, providing a potential therapeutic strategy in cancer treatments. PMID:26216063

  17. 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.

  18. Conformal Anomaly and Large Scale Gravitational Coupling

    CERN Document Server

    Salehi, H

    2000-01-01

    We present a model in which the breackdown of conformal symmetry of a quantum stress-tensor due to the trace anomaly is related to a cosmological effect in a gravitational model. This is done by characterizing the traceless part of the quantum stress-tensor in terms of the stress-tensor of a conformal invariant classical scalar field. We introduce a conformal frame in which the anomalous trace is identified with a cosmological constant. In this conformal frame we establish the Einstein field equations by connecting the quantum stress-tensor with the large scale distribution of matter in the universe.

  19. Conformal invariance conserved quantity of Hamilton systems

    Institute of Scientific and Technical Information of China (English)

    Cai Jian-Le; Luo Shao-Kai; Mei Feng-Xiang

    2008-01-01

    This paper studies conformal invariance and comserved quantRies of Hamilton system.The definition and the determining equation of conformal invariance for Hamilton system are provided.The relationship between the conformal invariance and the Lie symmetry are discussed,and the necessary and sufficient condition that the conformal invariance would be the Lie symmetry of the system under the infinitesimal one-parameter transformation group is deduced.It gives the conserved quantities of the system and an example for illustration.

  20. Approaching Conformality with Ten Flavors

    Energy Technology Data Exchange (ETDEWEB)

    Appelquist, Thomas; Brower, Richard C.; Buchoff, Michael I.; Cheng, Michael; Cohen, Saul D.; Fleming, George T.; Kiskis, Joe; Lin, Meifeng; Na, Heechang; Neil, Ethan T.; Osborn, James C.

    2012-04-01

    We present first results for lattice simulations, on a single volume, of the low-lying spectrum of an SU(3) Yang-Mills gauge theory with N{sub f} = 10 light fermions in the fundamental representation. Fits to the fermion mass dependence of various observables are found to be globally consistent with the hypothesis that this theory is within or just outside the strongly-coupled edge of the conformal window, with mass anomalous dimension {gamma}* {approx} 1 over the range of scales simulated. We stress that we cannot rule out the possibility of spontaneous chiral-symmetry breaking at scales well below our infrared cutoff. We discuss important systematic effects, including finite-volume corrections, and consider directions for future improvement.

  1. Approaching Conformality with Ten Flavors

    CERN Document Server

    Appelquist, Thomas; Buchoff, Michael I; Cheng, Michael; Cohen, Saul D; Fleming, George T; Kiskis, Joe; Lin, Meifeng; Na, Heechang; Neil, Ethan T; Osborn, James C; Rebbi, Claudio; Schaich, David; Schroeder, Chris; Voronov, Gennady; Vranas, Pavlos

    2012-01-01

    We present first results for lattice simulations, on a single volume, of the low-lying spectrum of an SU(3) Yang-Mills gauge theory with ten light fermions in the fundamental representation. Fits to the fermion mass dependence of various observables are found to be globally consistent with the hypothesis that this theory is within or just outside the strongly-coupled edge of the conformal window, with mass anomalous dimension approximately equal to 1 over the range of scales simulated. We stress that we cannot rule out the possibility of spontaneous chiral-symmetry breaking at scales well below our infrared cutoff. We discuss important systematic effects, including finite-volume corrections, and consider directions for future improvement.

  2. A conformal model of gravitons

    CERN Document Server

    Donoghue, John F

    2016-01-01

    In the description of general covariance, the vierbein and the Lorentz connection can be treated as independent fundamental fields. With the usual gauge Lagrangian, the Lorentz connection is characterized by an asymptotically free running coupling. When running from high energy, the coupling gets large at a scale which can be called the Planck mass. If the Lorentz connection is confined at that scale, the low energy theory can have the Einstein Lagrangian induced at low energy through dimensional transmutation. However, in general there will be new divergences in such a theory and the Lagrangian basis should be expanded. I construct a conformally invariant model with a larger basis size which potentially may have the same property.

  3. Charged gravastars admitting conformal motion

    CERN Document Server

    Usmani, A A; Ray, Saibal; Nandi, K K; Kuhfittig, Peter K F; Rakib, Sk A; Hasan, Z

    2010-01-01

    We propose a new model of a {\\it gravastar} admitting conformal motion. While retaining the framework of the Mazur-Mottola model, the gravastar is assumed to be internally charged, with an exterior defined by a Reissner-Nordstr{\\"o}m rather than a Schwarzschild line element. The solutions obtained involve (i) the interior region, (ii) the shell, and (iii) the exterior region of the sphere. Of these three cases the first case is of primary interest since the total gravitational mass vanishes for vanishing charge and turns the total gravitational mass into an {\\it electromagnetic mass} under certain conditions. This suggests that the interior de Sitter vacuum of a charged gravastar is essentially an electromagnetic mass model that must generate the gravitational mass. We have also analyzed various other aspects such as the stress energy tensor in the thin shell and the entropy of the system.

  4. 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.

  5. Gravitomagnetic effects in conformal gravity

    CERN Document Server

    Said, Jackson Levi; Adami, Kristian Zarb

    2014-01-01

    Gravitomagnetic effects are characterized by two phenomena: first, the geodetic effect which describes the precession of the spin of a gyroscope in a free orbit around a massive object, second, the Lense-Thirring effect which describes the precession of the orbital plane about a rotating source mass. We calculate both these effects in the fourth-order theory of conformal Weyl gravity for the test case of circular orbits. We show that for the geodetic effect a linear term arises which may be interesting for high radial orbits, whereas for the Lense-Thirring effect the additional term has a diminishing effect for most orbits. Circular orbits are also considered in general leading up to a generalization of Kepler's third law.

  6. Electromagnetic characterization of conformal antennas

    Science.gov (United States)

    Volakis, John L.; Kempel, Leo C.; Alexanian, Angelos; Jin, J. M.; Yu, C. L.; Woo, Alex C.

    1992-01-01

    The ultimate objective of this project is to develop a new technique which permits an accurate simulation of microstrip patch antennas or arrays with various feed, superstrate and/or substrate configurations residing in a recessed cavity whose aperture is planar, cylindrical or otherwise conformed to the substructure. The technique combines the finite element and boundary integral methods to formulate a system suitable for solution via the conjugate gradient method in conjunction with the fast Fourier transform. The final code is intended to compute both scattering and radiation patterns of the structure with an affordable memory demand. With upgraded capabilities, the four included papers examined the radar cross section (RCS), input impedance, gain, and resonant frequency of several rectangular configurations using different loading and substrate/superstrate configurations.

  7. Conformational regulation of charge recombination reactions in a photosynthetic bacterial reaction center

    DEFF Research Database (Denmark)

    Katona, Gergely; Snijder, Arjan; Gourdon, Pontus Emanuel;

    2005-01-01

    In bright light the photosynthetic reaction center (RC) of Rhodobacter sphaeroides stabilizes the P(+)(870).Q(-)(A) charge-separated state and thereby minimizes the potentially harmful effects of light saturation. Using X-ray diffraction we report a conformational change that occurs within the cy...

  8. The complex interplay between ligand binding and conformational structure of the folate binding protein (folate receptor)

    DEFF Research Database (Denmark)

    Holm, Jan; Bruun, Susanne Wrang; Hansen, Steen I.

    2015-01-01

    , and the binding induces a conformational change with formation of hydrophilic and stable holo-FBP. Holo-FBP exhibits a ligand-mediated concentration-dependent self-association into multimers of great thermal and chemical stability due to strong intermolecular forces. Both ligand and FBP are thus protected against...

  9. Effect of Protein Charge on the Generation of Aggregation-Prone Conformers

    NARCIS (Netherlands)

    Broersen, K.; Weijers, M.; Groot, de J.; Hamer, R.J.; Jongh, de H.H.J.

    2007-01-01

    This study describes how charge modification affects aggregation of ovalbumin, thereby distinguishing the role of conformational and electrostatic stability in the process. Ovalbumin variants were engineered using chemical methylation or succinylation to obtain a range of protein net charge from -1

  10. Effect of protein charge on the generation of aggregation-prone conformers

    NARCIS (Netherlands)

    Broersen, K.; Weijers, M.; Groot, J.de; Hamer, R.J.; Jongh, H.H.J.de

    2007-01-01

    This study describes how charge modification affects aggregation of ovalbumin, thereby distinguishing the role of conformational and electrostatic stability in the process. Ovalbumin variants were engineered using chemical methylation or succinylation to obtain a range of protein net charge from -1

  11. Triple helix conformation-specific blinking of Cy3 in DNA.

    Science.gov (United States)

    Kawai, Kiyohiko; Maruyama, Atsushi

    2015-03-21

    We report that Cy3 undergoes triple helix conformation-specific blinking in DNA. Blinking patterns were affected by the stabilization of the Hoogsteen base-pair, suggesting that not only the presence but also the fluctuating behaviour of the triple helix can be monitored by the changes in the Cy3 blinking patterns.

  12. Vortices in holographic superfluids and superconductors as conformal defects

    CERN Document Server

    Dias, Oscar J C; Iqbal, Nabil; Santos, Jorge E

    2013-01-01

    We present a detailed study of a single vortex in a holographic symmetry breaking phase. At low energies the system flows to an nontrivial conformal fixed point. Novel vortex physics arises from the interaction of these gapless degrees of freedom with the vortex: at low energies the vortex may be understood as a conformal defect in this low energy theory. Defect conformal symmetry allows the construction of a simple infrared geometry describing a new kind of extremal horizon: a Poincare horizon with a small bubble of magnetic Reissner-Nordstrom horizon inside it that carries a single unit of magnetic flux and a finite amount of entropy even at zero temperature. We also construct the full geometry describing the vortex at finite temperature in a UV complete theory. We study both superfluid and superconducting boundary conditions and calculate thermodynamic properties of the vortex. A study of vortex stability reveals that the dual superconductor can be Type I or Type II, depending on the charge of the condense...

  13. Crystal structure and conformational analysis of angiotensinogen fragments.

    Science.gov (United States)

    Benkoulouche, M; Cotrait, M; Geoffre, S; Precigoux, G

    1989-12-01

    The tripeptide acetyl-L-prolyl-L-phenylalanyl-L-histidine crystallizes in the orthorhombic space group P2(1)2(1)2(1) with eight molecules in a unit cell of dimensions a = 9.028(2), b = 140.54(6) and c = 42.41(1)A. The structure has been solved by direct methods and refined to an R value of 0.056 for 2904 observed reflections. The molecule exists as a zwitterion with terminal (His)CO2- and (imidazole)H+ as charged groups. The two peptide molecules in the structure adopt a type I beta-turn with Pro and Phe as the corner residues. The main conformational difference between the two crystallographically independent molecules is seen to be in the histidine side-chain orientations. The molecules arrange themselves in sheets perpendicular to the c axis. All hydrophobic side chains lie on one side of the sheets thus generated, whereas the hydrophilic groups are located on the other side. An interesting feature of the crystal structure is the existence of a water layer between adjacent peptide sheets. The conformational study of the isolated Ac-His-Pro-Phe-His-MA using energy calculations gives a rather limited number of stable conformers. The most stable corresponds to a type I beta-turn stabilized through two hydrogen bonds, followed by a less stable type II beta-turn (delta E = 2.0 kcal) and a partly helical structure (delta E = 2.6 kcal).

  14. Thermal adaptation of conformational dynamics in ribonuclease H.

    Directory of Open Access Journals (Sweden)

    Kate A Stafford

    Full Text Available The relationship between inherent internal conformational processes and enzymatic activity or thermodynamic stability of proteins has proven difficult to characterize. The study of homologous proteins with differing thermostabilities offers an especially useful approach for understanding the functional aspects of conformational dynamics. In particular, ribonuclease HI (RNase H, an 18 kD globular protein that hydrolyzes the RNA strand of RNA:DNA hybrid substrates, has been extensively studied by NMR spectroscopy to characterize the differences in dynamics between homologs from the mesophilic organism E. coli and the thermophilic organism T. thermophilus. Herein, molecular dynamics simulations are reported for five homologous RNase H proteins of varying thermostabilities and enzymatic activities from organisms of markedly different preferred growth temperatures. For the E. coli and T. thermophilus proteins, strong agreement is obtained between simulated and experimental values for NMR order parameters and for dynamically averaged chemical shifts, suggesting that these simulations can be a productive platform for predicting the effects of individual amino acid residues on dynamic behavior. Analyses of the simulations reveal that a single residue differentiates between two different and otherwise conserved dynamic processes in a region of the protein known to form part of the substrate-binding interface. Additional key residues within these two categories are identified through the temperature-dependence of these conformational processes.

  15. Solution conformation and dynamics of exopolysaccharides from Burkholderia species.

    Science.gov (United States)

    Pol-Fachin, Laercio; Serrato, Rodrigo V; Verli, Hugo

    2010-09-03

    Exopolysaccharides (EPSs) from the Burkholderia genus are proposed to be involved in pathological conditions in humans, such as cystic fibrosis and septicemia, as well as in the stability of soil aggregates. Hence, considering that the conformational and dynamic aspects of such EPSs may influence their biological activity, the current work employs a series of molecular dynamics simulations on di-, oligo-, and polysaccharide fragments of three EPSs, from Burkholderia caribensis, Burkholderia cepacia, and Burkholderia pseudomallei, with previously determined NOE data, to obtain a conformational description of such EPSs at the atomic level. As the obtained results show good agreement with the experimental data, pointing to the adequacy of the employed methodology to accurately describe the dynamics of polysaccharides, the strategy was also employed to predict the conformational behavior of an additional compound, from Burkholderia tropica, for which NOE signals are not available. Taking into account the potential importance of EPSs on the interaction of Burkholderia bacteria with distinct environments, it may be expected that a greater understanding of their structural aspects may contribute to controlling their pathological roles and potential agricultural applications.

  16. Testing Postural Stability: Are the Star Excursion Balance Test and Biodex Balance System Limits of Stability Tests Consistent?

    Science.gov (United States)

    Glave, A Page; Didier, Jennifer J; Weatherwax, Jacqueline; Browning, Sarah J; Fiaud, Vanessa

    2016-01-01

    There are a variety of options to test postural stability; however many physical tests lack validity information. Two tests of postural stability - the Star Excursion Balance Test (SEBT) and Biodex Balance System Limits of Stability Test (LOS) - were examined to determine if similar components of balance were measured. Healthy adults (n=31) completed the LOS (levels 6 and 12) and SEBT (both legs). SEBT directions were offset by 180° to approximate LOS direction. Correlations and partial correlations controlling for height were analyzed. Correlations were significant for SEBT 45° and LOS back-left (6: r=-0.41; 12: r=-0.42; pbalance. Research is needed to determine and define what specific components of balance are being assessed. Care must be taken when choosing balance tests to best match the test to the purpose of testing (fall risk, athletic performance, etc.).

  17. Conformal Higgs, or techni-dilaton- composite Higgs near conformality

    CERN Document Server

    Yamawaki, Koichi

    2010-01-01

    In contrast to the folklore that Technicolor (TC) is a "Higgsless theory", we shall discuss existence of a composite Higgs boson, Techni-Dilaton (TD), a pseudo-Nambu-Goldstone boson of the scale invariance in the Scale-invariant/Walking/Conformal TC (SWC TC) which generates a large anomalous dimension $\\gamma_m \\simeq 1$ in a wide region from the dynamical mass $m$ $= {\\cal O}$ (TeV) of the techni-fermion all the way up to the intrinsic scale $\\Lambda_{\\rm TC}$ of the SWC TC (analogue of $\\Lambda_{\\rm QCD}$), where $\\Lambda_{\\rm TC} $ is taken typically as the scale of the Extended TC scale $\\Lambda_{\\rm ETC}$: $\\Lambda_{\\rm TC} \\simeq \\Lambda_{\\rm ETC}\\sim10^3$ TeV $ (\\gg m)$. All the techni-hadrons have mass on the same order ${\\cal O} (m)$, which in SWC TC is extremely smaller than the intrinsic scale $\\Lambda_{\\rm TC} \\simeq \\Lambda_{\\rm ETC} $, in sharp contrast to QCD where both are of the same order. The mass of TD arises from the {\\it non-perturbative scale anomaly} associated with the techni-fermion ...

  18. Multidimensional separations of ubiquitin conformers in the gas phase: relating ion cross sections to H/D exchange measurements.

    Science.gov (United States)

    Robinson, Errol W; Williams, Evan R

    2005-09-01

    Investigating gas-phase structures of protein ions can lead to an improved understanding of intramolecular forces that play an important role in protein folding. Both hydrogen/deuterium (H/D) exchange and ion mobility spectrometry provide insight into the structures and stabilities of different gas-phase conformers, but how best to relate the results from these two methods has been hotly debated. Here, high-field asymmetric waveform ion mobility spectrometry (FAIMS) is combined with Fourier-transform ion cyclotron resonance mass spectrometry (FT/ICR MS) and is used to directly relate ubiquitin ion cross sections and H/D exchange extents. Multiple conformers can be identified using both methods. For the 9+ charge state of ubiquitin, two conformers (or unresolved populations of conformers) that have cross sections differing by 10% are resolved by FAIMS, but only one conformer is apparent using H/D exchange at short times. For the 12+ charge state, two conformers (or conformer populations) have cross sections differing by ion collisional cross sections and H/D exchange distributions are not strongly correlated and that factors other than surface accessibility appear to play a significant role in determining rates and extents of H/D exchange. Conformers that are not resolved by one method could be resolved by the other, indicating that these two methods are highly complementary and that more conformations can be resolved with this combination of methods than by either method alone.

  19. Canted magnetic ground state of quarter-doped manganites R 0.75Ca0.25MnO3 (R  =  Y, Tb, Dy, Ho, and Er)

    Science.gov (United States)

    Sinclair, R.; Cao, H. B.; Garlea, V. O.; Lee, M.; Choi, E. S.; Dun, Z. L.; Dong, S.; Dagotto, E.; Zhou, H. D.

    2017-02-01

    Polycrystalline samples of the quarter-doped manganites R 0.75Ca0.25MnO3 (R  =  Y, Tb, Dy, Ho, and Er) were studied by x-ray diffraction and AC/DC susceptibility measurements. All five samples are orthorhombic and exhibit similar magnetic properties: enhanced ferromagnetism below T 1 (∼80 K) and a spin glass (SG) state below T SG (∼30 K). With increasing R 3+ ionic size, both T 1 and T SG generally increase. The single crystal neutron diffraction results on Tb0.75Ca0.25MnO3 revealed that the SG state is mainly composed of a short-range ordered version of a novel canted (i.e. noncollinear) antiferromagnetic spin state. Furthermore, calculations based on the double exchange model for quarter-doped manganites reveal that this new magnetic phase provides a transition state between the ferromagnetic state and the theoretically predicted spin-orthogonal stripe phase.

  20. Neutron and magnetic studies of L a0.7S r0.3M n1 -xC rxO3 (x ≤0.7 ) : A homogeneous charge-ordered system

    Science.gov (United States)

    Creel, Thomas F.; Yang, Jinbo; Malik, Satish K.; Quezado, S.; Pringle, O. A.; Yelon, William B.; James, William J.

    2016-02-01

    Structural and magnetic properties of L a0.7S r0.3M n1 -xC rxO3(0

  1. The conformal approach to asymptotic analysis

    CERN Document Server

    Nicolas, Jean-Philippe

    2015-01-01

    This essay was written as an extended version of a talk given at a conference in Strasbourg on "Riemann, Einstein and geometry", organized by Athanase Papadopoulos in September 2014. Its aim is to present Roger Penrose's approach to asymptotic analysis in general relativity, which is based on conformal geometric techniques, focusing on historical and recent aspects of two specialized topics~: conformal scattering and peeling.

  2. Regular conformal system for Einstein equations

    Energy Technology Data Exchange (ETDEWEB)

    Choquet-Bruhat, Y.; Novello, M.

    1987-06-21

    We give a system of partial differential equations satisfied by a metric g conformal to an Einstein metric and by the conformal factor ..omega.., regular system in the sense that it does not contain negative powers of ..omega... We use the ideas of Friedrich but we obtain here a hyperbolic system in the sense of Leray, by a different method.

  3. Asymptotic symmetry algebra of conformal gravity

    CERN Document Server

    Irakleidou, M

    2016-01-01

    We compute asymptotic symmetry algebras of conformal gravity. Due to more general boundary conditions allowed in conformal gravity in comparison to those in Einstein gravity, we can classify the corresponding algebras. The highest algebra for non-trivial boundary conditions is five dimensional and it leads to global geon solution with non-vanishing charges.

  4. 40 CFR 52.138 - Conformity procedures.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 3 2010-07-01 2010-07-01 false Conformity procedures. 52.138 Section...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Arizona § 52.138 Conformity procedures. (a) Purpose. The... plans for metropolitan transportation planning organizations (MPOs) to use when determining...

  5. 14 CFR 17.45 - Conforming amendments.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Conforming amendments. 17.45 Section 17.45 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PROCEDURAL RULES PROCEDURES FOR PROTESTS AND CONTRACTS DISPUTES Finality and Review § 17.45 Conforming amendments. The...

  6. Conformity to Peer Pressure in Preschool Children

    Science.gov (United States)

    Haun, Daniel B. M.; Tomasello, Michael

    2011-01-01

    Both adults and adolescents often conform their behavior and opinions to peer groups, even when they themselves know better. The current study investigated this phenomenon in 24 groups of 4 children between 4;2 and 4;9 years of age. Children often made their judgments conform to those of 3 peers, who had made obviously erroneous but unanimous…

  7. An extension theorem for conformal gauge singularities

    CERN Document Server

    Tod, Paul

    2007-01-01

    We analyse conformal gauge, or isotropic, singularities in cosmological models in general relativity. Using the calculus of tractors, we find conditions in terms of tractor curvature for a local extension of the conformal structure through a cosmological singularity and prove a local extension theorem.

  8. Conformity to Peer Pressure in Preschool Children

    Science.gov (United States)

    Haun, Daniel B. M.; Tomasello, Michael

    2011-01-01

    Both adults and adolescents often conform their behavior and opinions to peer groups, even when they themselves know better. The current study investigated this phenomenon in 24 groups of 4 children between 4;2 and 4;9 years of age. Children often made their judgments conform to those of 3 peers, who had made obviously erroneous but unanimous…

  9. DIMENSIONS FOR RANDOM SELF-CONFORMAL SETS

    Institute of Scientific and Technical Information of China (English)

    Liu Yanyan; Wu Jun

    2003-01-01

    A set is called regular if its Hausdorff dimension and upper box-counting dimension coincide.In this paper,we prove that the random self-conformal set is regular almost surely.Also we determine the dimensions for a class of random self-conformal sets.

  10. Effects of sorbitol and glycerol on the structure, dynamics, and stability of Mycobacterium tuberculosis pyrazinamidase

    Directory of Open Access Journals (Sweden)

    Mehrnoosh Khajehzadeh

    2016-01-01

    Conclusion: It can be concluded that the native conformation of the enzyme was stabilized in the sorbitol and glycerol and tend to exclude from the PZase surface, forcing the enzyme to keep it in the compactly folded conformation. The glycerol molecules stabilized PZase by decreasing the loops flexibility and then compacting the enzyme structure. It appears that more stability of PZase in glycerol solution correlates with its amphiphilic orientation, which decreases the unfavorable interactions of hydrophobic regions.

  11. Stability Functions

    CERN Document Server

    Burns, Daniel; Wang, Zuoqin

    2008-01-01

    In this article we discuss the role of stability functions in geometric invariant theory and apply stability function techniques to problems in toric geometry. In particular we show how one can use these techniques to recover results of Burns-Guillemin-Uribe and Shiffman-Tate-Zelditch on asymptotic properties of sections of holomorphic line bundles over toric varieties.

  12. The Conformal Limit of Inflation in the Era of CMB Polarimetry

    CERN Document Server

    Pajer, Enrico; Van Wijck, Jaap V S

    2016-01-01

    We argue that the non-detection of primordial tensor modes has taught us a great deal about the primordial universe. In single-field slow-roll inflation, the current upper bound on the tensor-to-scalar ratio, $r < 0.07$ $(95 \\% ~CL)$, implies that the Hubble slow-roll parameters obey $\\varepsilon \\ll \\eta$, and therefore establishes the existence of a new hierarchy. We dub this regime the conformal limit of (slow-roll) inflation, and show that it includes Starobinsky-like inflation as well as all viable single-field models with a sub-Planckian field excursion. In this limit, all primordial correlators are constrained by the full conformal group to leading non-trivial order in slow-roll. This fixes the power spectrum and the full bispectrum, and leads to the "conformal" shape of non-Gaussianity. The size of non-Gaussianity is related to the running of the spectral index by a consistency condition, and therefore it is expected to be small. In passing, we clarify the role of boundary terms in the $\\zeta$ acti...

  13. Conformant Planning via Symbolic Model Checking

    CERN Document Server

    Cimatti, A; 10.1613/jair.774

    2011-01-01

    We tackle the problem of planning in nondeterministic domains, by presenting a new approach to conformant planning. Conformant planning is the problem of finding a sequence of actions that is guaranteed to achieve the goal despite the nondeterminism of the domain. Our approach is based on the representation of the planning domain as a finite state automaton. We use Symbolic Model Checking techniques, in particular Binary Decision Diagrams, to compactly represent and efficiently search the automaton. In this paper we make the following contributions. First, we present a general planning algorithm for conformant planning, which applies to fully nondeterministic domains, with uncertainty in the initial condition and in action effects. The algorithm is based on a breadth-first, backward search, and returns conformant plans of minimal length, if a solution to the planning problem exists, otherwise it terminates concluding that the problem admits no conformant solution. Second, we provide a symbolic representation ...

  14. On Combinatorial Expansions of Conformal Blocks

    CERN Document Server

    Marshakov, A; Morozov, A

    2009-01-01

    In a recent paper (arXiv:0906.3219) the representation of Nekrasov partition function in terms of nontrivial two-dimensional conformal field theory has been suggested. For non-vanishing value of the deformation parameter \\epsilon=\\epsilon_1+\\epsilon_2 the instanton partition function is identified with a conformal block of Liouville theory with the central charge c = 1+ 6\\epsilon^2/\\epsilon_1\\epsilon_2. If reversed, this observation means that the universal part of conformal blocks, which is the same for all two-dimensional conformal theories with non-degenerate Virasoro representations, possesses a non-trivial decomposition into sum over sets of the Young diagrams, different from the natural decomposition studied in conformal field theory. We provide some details about this intriguing new development in the simplest case of the four-point correlation functions.

  15. Finite Conformal Quantum Gravity and Nonsingular Spacetimes

    CERN Document Server

    Modesto, Leonardo

    2016-01-01

    We explicitly prove that a class of finite quantum gravitational theories (in odd as well as in even dimension) is actually a range of anomaly-free conformally invariant theories in the spontaneously broken phase of the conformal Weyl symmetry. At classical level we show how the Weyl conformal invariance is likely able to tame the spacetime singularities that plague not only Einstein gravity, but also local and weakly non-local higher derivative theories. This latter statement is rigorously proved by a singularity theorem that applies to a large class of weakly non-local theories. Following the seminal paper by Narlikar and Kembhavi, we provide an explicit construction of singularity-free black hole exact solutions conformally equivalent to the Schwarzschild metric. Furthermore, we show that the FRW cosmological solutions and the Belinski, Khalatnikov, Lifshitz (BKL) spacetimes, which exactly solve the classical equations of motion, are conformally equivalent to regular spacetimes. Finally, we prove that the ...

  16. Permeable conformal walls and holography

    Science.gov (United States)

    Bachas, Constantin; de Boer, Jan; Dijkgraaf, Robbert; Ooguri, Hirosi

    2002-06-01

    We study conformal field theories in two dimensions separated by domain walls, which preserve at least one Virasoro algebra. We develop tools to study such domain walls, extending and clarifying the concept of `folding' discussed in the condensed-matter literature. We analyze the conditions for unbroken supersymmetry, and discuss the holographic duals in AdS3 when they exist. One of the interesting observables is the Casimir energy between a wall and an anti-wall. When these separate free scalar field theories with different target-space radii, the Casimir energy is given by the dilogarithm function of the reflection probability. The walls with holographic duals in AdS3 separate two sigma models, whose target spaces are moduli spaces of Yang-Mills instantons on T4 or K3. In the supergravity limit, the Casimir energy is computable as classical energy of a brane that connects the walls through AdS3. We compare this result with expectations from the sigma-model point of view.

  17. Permeable conformal walls and holography

    CERN Document Server

    Bachas, C P; Dijkgraaf, R; Ooguri, H

    2002-01-01

    We study conformal field theories in two dimensions separated by domain walls, which preserve at least one Virasoro algebra. We develop tools to study such domain walls, extending and clarifying the concept of `folding' discussed in the condensed-matter literature. We analyze the conditions for unbroken supersymmetry, and discuss the holographic duals in AdS3 when they exist. One of the interesting observables is the Casimir energy between a wall and an anti-wall. When these separate free scalar field theories with different target-space radii, the Casimir energy is given by the dilogarithm function of the reflection probability. The walls with holographic duals in AdS3 separate two sigma models, whose target spaces are moduli spaces of Yang-Mills instantons on T4 or K3. In the supergravity limit, the Casimir energy is computable as classical energy of a brane that connects the walls through AdS3. We compare this result with expectations from the sigma-model point of view.

  18. Cosmology in Conformally Flat Spacetime

    Science.gov (United States)

    Endean, Geoffrey

    1997-04-01

    A possible solution to cosmological age and redshift-distance difficulties has recently been proposed by applying the appropriate conformally flat spacetime (CFS) coordinates to the standard solution of the field equations in a standard dust model closed universe. Here it is shown that CFS time correctly measures the true age of the universe, thus answering a major theoretical objection to the proposal. It is also shown that the CFS interpretation leads to a strong Copernican principle and is in all other respects wholly self-consistent. The deceleration parameter q0 is related to t0, the present age of the universe divided by L, the scale length of its curvature (an absolute constant). The values of q0 and L are approximately 5/6 and 9.2 × 109 yr, respectively. It is shown that the universe started everywhere simultaneously, with no recession velocity until the effects of its closed topology became significant. Conclusions to the contrary in standard theory (the big bang) stem from a different definition of recession velocity. The theoretical present cosmological mass density is quantified as 4.4 × 10-27 kg m-3 approximately, thus greatly reducing, in a closed universe, the observational requirement to find hidden mass. It is also shown that the prediction of standard theory, for a closed universe, of collapse toward a big crunch termination, will not in fact take place.

  19. Conforming Morse-Smale Complexes.

    Science.gov (United States)

    Gyulassy, Attila; Günther, David; Levine, Joshua A; Tierny, Julien; Pascucci, Valerio

    2014-12-01

    Morse-Smale (MS) complexes have been gaining popularity as a tool for feature-driven data analysis and visualization. However, the quality of their geometric embedding and the sole dependence on the input scalar field data can limit their applicability when expressing application-dependent features. In this paper we introduce a new combinatorial technique to compute an MS complex that conforms to both an input scalar field and an additional, prior segmentation of the domain. The segmentation constrains the MS complex computation guaranteeing that boundaries in the segmentation are captured as separatrices of the MS complex. We demonstrate the utility and versatility of our approach with two applications. First, we use streamline integration to determine numerically computed basins/mountains and use the resulting segmentation as an input to our algorithm. This strategy enables the incorporation of prior flow path knowledge, effectively resulting in an MS complex that is as geometrically accurate as the employed numerical integration. Our second use case is motivated by the observation that often the data itself does not explicitly contain features known to be present by a domain expert. We introduce edit operations for MS complexes so that a user can directly modify their features while maintaining all the advantages of a robust topology-based representation.

  20. Cholesterol-dependent conformational changes of P-glycoprotein are detected by the 15D3 monoclonal antibody.

    Science.gov (United States)

    Gutay-Tóth, Zsuzsanna; Fenyvesi, Ferenc; Bársony, Orsolya; Szente, Lajos; Goda, Katalin; Szabó, Gábor; Bacsó, Zsolt

    2016-03-01

    The 15D3 mouse monoclonal antibody (mAb) binds an uncharacterized extracellular epitope of the ATP Binding Cassette (ABC) transporter human P-glycoprotein (Pgp). Depletion of cell plasma membrane cholesterol by using methyl-β-cyclodextrin or other chemically modified β-cyclodextrins decreased the Pgp binding affinity of 15D3 mAb. UIC2 mAb, which is known to distinguish two conformers of this ABC transporter, binds only a fraction of cell surface Pgps. UIC2 mAb non-reactive pools of Pgp can be identified with other extracellular mAbs such as 15D3. Cyclosporin A (CsA) can shift non-reactive Pgps into their UIC2-reactive conformation: a phenomenon called the "UIC2 shift". Competition studies proposed these two mAbs share overlapping epitopes and can reveal conformational changes of Pgp that correlate (r=0.97) with the cholesterol content of cells. An apparent increase in competition of these mAbs suggested a conformational change similar to those found in the presence of CsA. However, the reason turned out not to be the UIC2-shift because cholesterol removal from the plasma membrane (PM) reduced the amount of detectable Pgps by 15D3 mAb. This study showed that 15D3 mAb bound to a conformation sensitive epitope of Pgp that was responsive to PM cholesterol levels. These conformational changes were gradual and not as great as the changes observed between the two conformers recognized by the UIC2 mAb.