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Sample records for inactive conformational states

  1. Preferential binding of allosteric modulators to active and inactive conformational states of metabotropic glutamate receptors

    Directory of Open Access Journals (Sweden)

    Klein-Seetharaman Judith

    2008-02-01

    Full Text Available Abstract Metabotropic glutamate receptors (mGluRs are G protein coupled receptors that play important roles in synaptic plasticity and other neuro-physiological and pathological processes. Allosteric mGluR ligands are particularly promising drug targets because of their modulatory effects – enhancing or suppressing the response of mGluRs to glutamate. The mechanism by which this modulation occurs is not known. Here, we propose the hypothesis that positive and negative modulators will differentially stabilize the active and inactive conformations of the receptors, respectively. To test this hypothesis, we have generated computational models of the transmembrane regions of different mGluR subtypes in two different conformations. The inactive conformation was modeled using the crystal structure of the inactive, dark state of rhodopsin as template and the active conformation was created based on a recent model of the light-activated state of rhodopsin. Ligands for which the nature of their allosteric effects on mGluRs is experimentally known were docked to the modeled mGluR structures using ArgusLab and Autodock softwares. We find that the allosteric ligand binding pockets of mGluRs are overlapping with the retinal binding pocket of rhodopsin, and that ligands have strong preferences for the active and inactive states depending on their modulatory nature. In 8 out of 14 cases (57%, the negative modulators bound the inactive conformations with significant preference using both docking programs, and 6 out of 9 cases (67%, the positive modulators bound the active conformations. Considering results by the individual programs only, even higher correlations were observed: 12/14 (86% and 8/9 (89% for ArgusLab and 10/14 (71% and 7/9 (78% for AutoDock. These findings strongly support the hypothesis that mGluR allosteric modulation occurs via stabilization of different conformations analogous to those identified in rhodopsin where they are induced by

  2. Catalysis by Glomerella cingulata cutinase requires conformational cycling between the active and inactive states of its catalytic triad.

    Science.gov (United States)

    Nyon, Mun Peak; Rice, David W; Berrisford, John M; Hounslow, Andrea M; Moir, Arthur J G; Huang, Huazhang; Nathan, Sheila; Mahadi, Nor Muhammad; Bakar, Farah Diba Abu; Craven, C Jeremy

    2009-01-09

    Cutinase belongs to a group of enzymes that catalyze the hydrolysis of esters and triglycerides. Structural studies on the enzyme from Fusarium solani have revealed the presence of a classic catalytic triad that has been implicated in the enzyme's mechanism. We have solved the crystal structure of Glomerella cingulata cutinase in the absence and in the presence of the inhibitors E600 (diethyl p-nitrophenyl phosphate) and PETFP (3-phenethylthio-1,1,1-trifluoropropan-2-one) to resolutions between 2.6 and 1.9 A. Analysis of these structures reveals that the catalytic triad (Ser136, Asp191, and His204) adopts an unusual configuration with the putative essential histidine His204 swung out of the active site into a position where it is unable to participate in catalysis, with the imidazole ring 11 A away from its expected position. Solution-state NMR experiments are consistent with the disrupted configuration of the triad observed crystallographically. H204N, a site-directed mutant, was shown to be catalytically inactive, confirming the importance of this residue in the enzyme mechanism. These findings suggest that, during its catalytic cycle, cutinase undergoes a significant conformational rearrangement converting the loop bearing the histidine from an inactive conformation, in which the histidine of the triad is solvent exposed, to an active conformation, in which the triad assumes a classic configuration.

  3. Ligand induced change of β2 adrenergic receptor from active to inactive conformation and its implication for the closed/open state of the water channel: insight from molecular dynamics simulation, free energy calculation and Markov state model analysis.

    Science.gov (United States)

    Bai, Qifeng; Pérez-Sánchez, Horacio; Zhang, Yang; Shao, Yonghua; Shi, Danfeng; Liu, Huanxiang; Yao, Xiaojun

    2014-08-14

    The reported crystal structures of β2 adrenergic receptor (β2AR) reveal that the open and closed states of the water channel are correlated with the inactive and active conformations of β2AR. However, more details about the process by which the water channel states are affected by the active to inactive conformational change of β2AR remain illusive. In this work, molecular dynamics simulations are performed to study the dynamical inactive and active conformational change of β2AR induced by inverse agonist ICI 118,551. Markov state model analysis and free energy calculation are employed to explore the open and close states of the water channel. The simulation results show that inverse agonist ICI 118,551 can induce water channel opening during the conformational transition of β2AR. Markov state model (MSM) analysis proves that the energy contour can be divided into seven states. States S1, S2 and S5, which represent the active conformation of β2AR, show that the water channel is in the closed state, while states S4 and S6, which correspond to the intermediate state conformation of β2AR, indicate the water channel opens gradually. State S7, which represents the inactive structure of β2AR, corresponds to the full open state of the water channel. The opening mechanism of the water channel is involved in the ligand-induced conformational change of β2AR. These results can provide useful information for understanding the opening mechanism of the water channel and will be useful for the rational design of potent inverse agonists of β2AR.

  4. On the conformational state of photoinactivated tyrosinase

    International Nuclear Information System (INIS)

    Khan, I.A.; Ali, R.

    1985-01-01

    Ultraviolet irradiation of tyrosinase rapidly decreased the dopa oxidase activity of the enzyme. Hydrodynamic, kinetic and thermodynamic parameters revealed gross differences in the native and photoinactivated states of the enzyme. The native state of tyrosinase was characterized as a tetramer with a compact, globular and rigid conformation. However, the photoinactivated state of tyrosinase was thermodynamically less stable and unusually sensitive to temperatures as low as 35 0 C. From the dose dependent loss in conformational integrity, thermodynamic stability and catalytic activity of tyrosinase, it is speculated that there are various structural segments distributed throughout the enzyme molecule. These structural segments act as centres of major molecular forces which hold the tetrameric enzyme into a compact and globular conformation. UV modification of these segments triggers a series of conformational changes leading to formation of a partially unfolded and catalytically inactive form of tyrosinase. (author)

  5. Antimicrobial and conformational studies of the active and inactive analogues of the protegrin-1 peptide.

    Science.gov (United States)

    Rodziewicz-Motowidło, Sylwia; Mickiewicz, Beata; Greber, Katarzyna; Sikorska, Emilia; Szultka, Lukasz; Kamysz, Elzbieta; Kamysz, Wojciech

    2010-02-01

    The natural antimicrobial cationic peptide protegrin-1 displays a broad spectrum of antimicrobial activity and rapidly kills pathogens by interacting with their cell membrane. We investigated the structure-activity relationships of three protegrin-1 analogues: IB-367 (RGGLCYCRGRFCVCVGR-NH(2)), BM-1 (RGLCYCRGRFCVCVG-NH(2)) and BM-2 (RGLCYRPRFVCVG-NH(2)). Our antimicrobial and antifungal activity studies of these peptides showed that BM-1 was much more active than IB-367 against Gram-positive bacteria and fungi, whereas BM-2 was inactive. The BM-1 peptide showed fourfold reduced haemolysis relative to IB-367, an additional advantage of this peptide. In addition, BM-1 was about 15% cheaper than IB-367 to synthesize. The absence of two cysteine residues in the BM-2 sequence could be the main reason for its unstable conformation and antimicrobial inactivity. The solution structures of these peptides were determined in dimethyl sulphoxide using two-dimensional NMR and restrained molecular dynamics calculations. IB-367 and BM-1 formed short, antiparallel, beta-hairpin structures connected by a type II' beta-turn. The shorter, inactive BM-2 analogue exhibited major and minor conformations (predominantly unordered) in the NMR spectra and was much more flexible.

  6. Steady states in conformal theories

    CERN Multimedia

    CERN. Geneva

    2015-01-01

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

  7. 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

  8. Interconversion of active and inactive conformations of urokinase-type plasminogen activator

    DEFF Research Database (Denmark)

    Liu, Zhuo; Kromann-Hansen, Tobias; Lund, Ida K.

    2012-01-01

    The catalytic activity of serine proteases depends on a salt-bridge between the amino group of residue 16 and the side chain of Asp194. The salt-bridge stabilizes the oxyanion hole and the S1 specificity pocket of the protease. Some serine proteases exist in only partially active forms, in which...... active state. Both a monoclonal antibody (mU3) and a peptidic inhibitor (mupain-1--16) stabilize the active state. The epitope of mU3 is located in the 37- and 70-loops at a site homologous to exosite I of thrombin. The N-terminus((Ile16)) of muPA((16--243)) was less exposed upon binding of mU3 or mupain......-1--16. In contrast, introduction of the mutations F40Y or E137A into muPA((16--243)) increased exposure of the N-terminus((Ile16)) and resulted in large changes in the thermodynamic parameters for mupain-1--16 binding. We conclude that the distorted state of muPA((16--243)) is conformationally...

  9. Conformation Generation: The State of the Art.

    Science.gov (United States)

    Hawkins, Paul C D

    2017-08-28

    The generation of conformations for small molecules is a problem of continuing interest in cheminformatics and computational drug discovery. This review will present an overview of methods used to sample conformational space, focusing on those methods designed for organic molecules commonly of interest in drug discovery. Different approaches to both the sampling of conformational space and the scoring of conformational stability will be compared and contrasted, with an emphasis on those methods suitable for conformer sampling of large numbers of drug-like molecules. Particular attention will be devoted to the appropriate utilization of information from experimental solid-state structures in validating and evaluating the performance of these tools. The review will conclude with some areas worthy of further investigation.

  10. Small molecule stabilization of the KSR inactive state antagonizes oncogenic Ras signalling.

    Science.gov (United States)

    Dhawan, Neil S; Scopton, Alex P; Dar, Arvin C

    2016-09-01

    Deregulation of the Ras-mitogen activated protein kinase (MAPK) pathway is an early event in many different cancers and a key driver of resistance to targeted therapies. Sustained signalling through this pathway is caused most often by mutations in K-Ras, which biochemically favours the stabilization of active RAF signalling complexes. Kinase suppressor of Ras (KSR) is a MAPK scaffold that is subject to allosteric regulation through dimerization with RAF. Direct targeting of KSR could have important therapeutic implications for cancer; however, testing this hypothesis has been difficult owing to a lack of small-molecule antagonists of KSR function. Guided by KSR mutations that selectively suppress oncogenic, but not wild-type, Ras signalling, we developed a class of compounds that stabilize a previously unrecognized inactive state of KSR. These compounds, exemplified by APS-2-79, modulate KSR-dependent MAPK signalling by antagonizing RAF heterodimerization as well as the conformational changes required for phosphorylation and activation of KSR-bound MEK (mitogen-activated protein kinase kinase). Furthermore, APS-2-79 increased the potency of several MEK inhibitors specifically within Ras-mutant cell lines by antagonizing release of negative feedback signalling, demonstrating the potential of targeting KSR to improve the efficacy of current MAPK inhibitors. These results reveal conformational switching in KSR as a druggable regulator of oncogenic Ras, and further suggest co-targeting of enzymatic and scaffolding activities within Ras-MAPK signalling complexes as a therapeutic strategy for overcoming Ras-driven cancers.

  11. Modification of the ATP inhibitory site of the Ascaris suum phosphofructokinase results in the stabilization of an inactive T state

    Energy Technology Data Exchange (ETDEWEB)

    Rao, G.S.J.; Cook, P.F.; Harris, B.G. (Univ. of North Texas, Fort Worth (United States))

    1991-10-15

    Treatment of the Ascaris suum phosphofructokinase (PFK) with 2{prime},3{prime}-dialdehyde ATP (oATP) results in an enzyme form that is inactive. The conformational integrity of the active site, however, is preserved, suggesting that oATP modification locks the PFK into an inactive T state that cannot be activated. A rapid, irreversible first-order inactivation of the PFK is observed in the presence of oATP. The rate of inactivation is saturable and gives a K{sub oATP} of 1.07 {plus minus} 0.27 mM. Complete protection against inactivation is afforded by high concentrations of ATP. This desensitized enzyme incorporates only 0.2-0.3 mol of ({sup 3}H)oATP/subunit, suggesting that in te native enzyme inactivation perhaps results from the modification of the ATP inhibitory site rather than the catalytic site. Modification of an active-site thiol by 4,4{prime}-dithiodipyridine is prevented yb ATP before and after oATP treatment. Finally, gel filtration HPLC studies show that the oATP-modified enzyme retains its tetrameric state and neither the tryptophan fluorescence nor the circular dichroic spectra of the modified enzyme are affected by fructose 2,6-bisphosphate, suggesting that the enzyme is locked into a tetrameric inactive T state.

  12. Solid state conformational classification of eight-membered rings

    DEFF Research Database (Denmark)

    Pérez, J.; García, L.; Kessler, M.

    2005-01-01

    A statistical classification of the solid state conformation in the title complexes using data retrieved from the Cambridge Structural Database (CSD) has been made. Phosphate and phosphinate complexes show a chair conformation preferably. In phosphonate complexes, the most frequent conformations...

  13. Structural studies of conformational changes of proteins upon phosphorylation: Structures of activated CheY, CheY-N16-FliM complex, and AAA + ATPase domain of NtrC1 in both inactive and active states

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seok-Yong [Univ. of California, Berkeley, CA (United States)

    2003-04-10

    Protein phosphorylation is a general mechanism for signal transduction as well as regulation of cellular function. Unlike phosphorylation in eukaryotic systems that uses Ser/Thr for the sites of modification, two-component signal transduction systems, which are prevalent in bacteria, archea, and lower eukaryotes, use an aspartate as the site of phosphorylation. Two-component systems comprise a histidine kinase and a receiver domain. The conformational change of the receiver domain upon phosphorylation leads to signal transfer to the downstream target, a process that had not been understood well at the molecular level. The transient nature of the phospho-Asp bond had made structural studies difficult. The discovery of an excellent analogue for acylphosphate, BeF3-, enabled structural study of activated receiver domains. The structure of activated Chemotaxis protein Y (CheY) was determined both by NMR spectroscopy and X-ray crystallography. These structures revealed the molecular basis of the conformational change that is coupled to phosphorylation. Phosphorylation of the conserved Asp residue in the active site allows hydrogen bonding of the T87 Oγ to phospho-aspartate, which in turn leads to the rotation of Y106 into the ''in'' position (termed Y-T coupling). The structure of activated CheY complexed with the 16 N-terminal residues of FliM (N16-FliM), its target, was also determined by X-ray crystallography and confirmed the proposed mechanism of activation (Y-T coupling). First, N16-FliM binds to the region on CheY that undergoes a significant conformational change. Second, the ''in'' position of Y106 presents a better binding surface for FliM because the sidechain of Y106 in the inactive form of CheY (''out'' position) sterically interferes with binding of N16-FliM. In addition to confirmation of Y-T coupling, the structure of the activated CheY-N16-FliM complex suggested that the

  14. Inactive and active states and supramolecular organization of GPCRs: insights from computational modeling

    Science.gov (United States)

    Fanelli, Francesca; De Benedetti, Pier G.

    2006-08-01

    Herein we make an overview of the results of our computational experiments aimed at gaining insight into the molecular mechanisms of GPCR functioning either in their normal conditions or when hit by gain-of-function or loss-of-function mutations. Molecular simulations of a number of GPCRs in their wild type and mutated as well as free and ligand-bound forms were instrumental in inferring the structural features, which differentiate the mutation- and ligand-induced active from the inactive states. These features essentially reside in the interaction pattern of the E/DRY arginine and in the degree of solvent exposure of selected cytosolic domains. Indeed, the active states differ from the inactive ones in the weakening of the interactions made by the highly conserved arginine and in the increase in solvent accessibility of the cytosolic interface between helices 3 and 6. Where possible, the structural hallmarks of the active and inactive receptor states are translated into molecular descriptors useful for in silico functional screening of novel receptor mutants or ligands. Computational modeling of the supramolecular organization of GPCRs and their intracellular partners is the current challenge toward a deep understanding of their functioning mechanisms.

  15. Search for Active-State Conformation of Drug Target GPCR Using Real-Coded Genetic Algorithm

    Science.gov (United States)

    Ishino, Yoko; Harada, Takanori; Aida, Misako

    G-Protein coupled receptors (GPCRs) comprise a large superfamily of proteins and are a target for nearly 50% of drugs in clinical use today. GPCRs have a unique structural motif, seven transmembrane helices, and it is known that agonists and antagonists dock with a GPCR in its ``active'' and ``inactive'' condition, respectively. Knowing conformations of both states is eagerly anticipated for elucidation of drug action mechanism. Since GPCRs are difficult to crystallize, the 3D structures of these receptors have not yet been determined by X-ray crystallography, except the inactive-state conformation of two proteins. The conformation of them enabled the inactive form of other GPCRs to be modeled by computer-aided homology modeling. However, to date, the active form of GPCRs has not been solved. This paper describes a novel method to predict the 3D structure of an active-state GPCR aiming at molecular docking-based virtual screening using real-coded genetic algorithm (real-coded GA), receptor-ligand docking simulations, and molecular dynamics (MD) simulations. The basic idea of the method is that the MD is first used to calculate an average 3D coordinates of all atoms of a GPCR protein against heat fluctuation on the pico- or nano- second time scale, and then real-coded GA involving receptor-ligand docking simulations functions to determine the rotation angle of each helix as a movement on wider time scale. The method was validated using human leukotriene B4 receptor BLT1 as a sample GPCR. Our study demonstrated that the established evolutionary search for the active state of the leukotriene receptor provided the appropriate 3D structure of the receptor to dock with its agonists.

  16. Radium-226 in plants and substrates at inactive uranium mill sites in the southwestern United States

    International Nuclear Information System (INIS)

    Marple, M.L.; Potter, L.D.

    1982-01-01

    The uptake and translocation of contaminants from uranium mill tailings piles and other similar wastes could be an important transport mechanism of these contaminants into the environment. The content of Ra-226, the radionuclide of most concern in this context, was investigated in plants growing on inactive uranium mill tailings sites in Four Corners Region of the southwestern United States and in plants grown under greenhouse conditions with minimal surficial contamination. This study provides a basis for estimating intake levels for herbivores and for evaluating transfer coefficients

  17. Decay of an active GPCR: Conformational dynamics govern agonist rebinding and persistence of an active, yet empty, receptor state.

    Science.gov (United States)

    Schafer, Christopher T; Fay, Jonathan F; Janz, Jay M; Farrens, David L

    2016-10-18

    Here, we describe two insights into the role of receptor conformational dynamics during agonist release (all-trans retinal, ATR) from the visual G protein-coupled receptor (GPCR) rhodopsin. First, we show that, after light activation, ATR can continually release and rebind to any receptor remaining in an active-like conformation. As with other GPCRs, we observe that this equilibrium can be shifted by either promoting the active-like population or increasing the agonist concentration. Second, we find that during decay of the signaling state an active-like, yet empty, receptor conformation can transiently persist after retinal release, before the receptor ultimately collapses into an inactive conformation. The latter conclusion is based on time-resolved, site-directed fluorescence labeling experiments that show a small, but reproducible, lag between the retinal leaving the protein and return of transmembrane helix 6 (TM6) to the inactive conformation, as determined from tryptophan-induced quenching studies. Accelerating Schiff base hydrolysis and subsequent ATR dissociation, either by addition of hydroxylamine or introduction of mutations, further increased the time lag between ATR release and TM6 movement. These observations show that rhodopsin can bind its agonist in equilibrium like a traditional GPCR, provide evidence that an active GPCR conformation can persist even after agonist release, and raise the possibility of targeting this key photoreceptor protein by traditional pharmaceutical-based treatments.

  18. Interconversion of active and inactive 30 S ribosomal subunits is accompanied by a conformational change in the decoding region of 16 S rRNA

    DEFF Research Database (Denmark)

    Moazed, D; Van Stolk, B J; Douthwaite, S

    1986-01-01

    of native structure, such as that which is observed under conditions of more severe ion depletion. Instead, it has the appearance of a reciprocal interconversion between two differently structured states; some bases become more reactive toward the probes, whilst others become less reactive as a result...... show reciprocal behavior at their N-1 versus N-7 positions. G926 loses its reactivity at N-1, but becomes highly reactive at N-7 as a result of the transition of the inactive state. In contrast, A1398 and G1401 become reactive at N-1, but lose their hyper-reactivity at N-7. The possible structural...

  19. Molecular Dynamics Simulations and Classical Multidimensional Scaling Unveil New Metastable States in the Conformational Landscape of CDK2.

    Directory of Open Access Journals (Sweden)

    Pasquale Pisani

    Full Text Available Protein kinases are key regulatory nodes in cellular networks and their function has been shown to be intimately coupled with their structural flexibility. However, understanding the key structural mechanisms of large conformational transitions remains a difficult task. CDK2 is a crucial regulator of cell cycle. Its activity is finely tuned by Cyclin E/A and the catalytic segment phosphorylation, whereas its deregulation occurs in many types of cancer. ATP competitive inhibitors have failed to be approved for clinical use due to toxicity issues raised by a lack of selectivity. However, in the last few years type III allosteric inhibitors have emerged as an alternative strategy to selectively modulate CDK2 activity. In this study we have investigated the conformational variability of CDK2. A low dimensional conformational landscape of CDK2 was modeled using classical multidimensional scaling on a set of 255 crystal structures. Microsecond-scale plain and accelerated MD simulations were used to populate this landscape by using an out-of-sample extension of multidimensional scaling. CDK2 was simulated in the apo-form and in complex with the allosteric inhibitor 8-anilino-1-napthalenesulfonic acid (ANS. The apo-CDK2 landscape analysis showed a conformational equilibrium between an Src-like inactive conformation and an active-like form. These two states are separated by different metastable states that share hybrid structural features with both forms of the kinase. In contrast, the CDK2/ANS complex landscape is compatible with a conformational selection picture where the binding of ANS in proximity of the αC helix causes a population shift toward the inactive conformation. Interestingly, the new metastable states could enlarge the pool of candidate structures for the development of selective allosteric CDK2 inhibitors. The method here presented should not be limited to the CDK2 case but could be used to systematically unmask similar mechanisms

  20. A conformal field theory description of fractional quantum Hall states

    NARCIS (Netherlands)

    Ardonne, E.

    2002-01-01

    In this thesis, we give a description of fractional quantum Hall states in terms of conformal field theory (CFT). As was known for a long time, the Laughlin states could be written in terms of correlators of chiral vertex operators of a c=1 CFT. It was shown by G. Moore and N. Read that more general

  1. Conformational States of the Spiropyran Molecule

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    Olha Kovalenko

    2015-01-01

    Full Text Available The form of the potential surface of the ground state was investigated on the basis of indoline spiropyran. As a result of this work the rotamers of an open-ring form of the spiropyran molecule were discovered, and the existence of the most probable rotamers was justified. The 3D potential surface of the ground state of the spiropyran molecule was built. The route of the isomerization of the molecule was discovered and values of barriers for this reaction were found. The part of the isomerization route that is responsible for changing the hybridization of spiroatom from sp3 to sp2 was found.

  2. Madumycin II inhibits peptide bond formation by forcing the peptidyl transferase center into an inactive state

    Energy Technology Data Exchange (ETDEWEB)

    Osterman, Ilya A.; Khabibullina, Nelli F.; Komarova, Ekaterina S.; Kasatsky, Pavel; Kartsev, Victor G.; Bogdanov, Alexey A.; Dontsova, Olga A.; Konevega, Andrey L.; Sergiev, Petr V.; Polikanov, Yury S. (InterBioScreen); (UIC); (MSU-Russia); (Kurchatov)

    2017-05-13

    The emergence of multi-drug resistant bacteria is limiting the effectiveness of commonly used antibiotics, which spurs a renewed interest in revisiting older and poorly studied drugs. Streptogramins A is a class of protein synthesis inhibitors that target the peptidyl transferase center (PTC) on the large subunit of the ribosome. In this work, we have revealed the mode of action of the PTC inhibitor madumycin II, an alanine-containing streptogramin A antibiotic, in the context of a functional 70S ribosome containing tRNA substrates. Madumycin II inhibits the ribosome prior to the first cycle of peptide bond formation. It allows binding of the tRNAs to the ribosomal A and P sites, but prevents correct positioning of their CCA-ends into the PTC thus making peptide bond formation impossible. We also revealed a previously unseen drug-induced rearrangement of nucleotides U2506 and U2585 of the 23S rRNA resulting in the formation of the U2506•G2583 wobble pair that was attributed to a catalytically inactive state of the PTC. The structural and biochemical data reported here expand our knowledge on the fundamental mechanisms by which peptidyl transferase inhibitors modulate the catalytic activity of the ribosome.

  3. Phospholipase C-related catalytically inactive protein can regulate obesity, a state of peripheral inflammation

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    Yosuke Yamawaki

    2017-02-01

    Full Text Available Obesity is defined as abnormal or excessive fat accumulation. Chronic inflammation in fat influences the development of obesity-related diseases. Many reports state that obesity increases the risk of morbidity in many diseases, including hypertension, dyslipidemia, type 2 diabetes, coronary heart disease, stroke, sleep apnea, and breast, prostate and colon cancers, leading to increased mortality. Obesity is also associated with chronic neuropathologic conditions such as depression and Alzheimer's disease. However, there is strong evidence that weight loss reduces these risks, by limiting blood pressure and improving levels of serum triglycerides, total cholesterol, low-density lipoprotein (LDL-cholesterol, and high-density lipoprotein (HDL-cholesterol. Prevention and control of obesity is complex, and requires a multifaceted approach. The elucidation of molecular mechanisms driving fat metabolism (adipogenesis and lipolysis aims at developing clinical treatments to control obesity. We recently reported a new regulatory mechanism in fat metabolism: a protein phosphatase binding protein, phospholipase C-related catalytically inactive protein (PRIP, regulates lipolysis in white adipocytes and heat production in brown adipocytes via phosphoregulation. Deficiency of PRIP in mice led to reduced fat accumulation and increased energy expenditure, resulting in a lean phenotype. Here, we evaluate PRIP as a new therapeutic target for the control of obesity.

  4. 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.

  5. Conformational Sub-states and Populations in Enzyme Catalysis

    Energy Technology Data Exchange (ETDEWEB)

    Agarwal, Pratul K [ORNL; Doucet, Nicholas [INRS-Institut Armand-Frappier, University of Quebec; Chennubholta, C [University of Pittsburgh; Ramanathan, Arvind [ORNL

    2016-01-01

    reactants in the active site, chemical turnover, and release of products. In addition to formation of crucial structural interactions between enzyme and substrate(s), coordinated motions within the enzyme substrate complex allow reaction to proceed at a much faster rate, compared to the reaction in solution and in the absence of enzyme. An increasing number of enzyme systems show the presence of conserved protein motions that are important for function. A wide variety of motions are naturally sampled (over femtosecond to millisecond time-scales) as the enzyme complex moves along the energetic landscape, driven by temperature and dynamical events from the surrounding environment. Areas of low energy along the landscape form conformational sub-states, which show higher conformational populations than surrounding areas. A small number of these protein conformational sub-states contain functionally important structural and dynamical features, which assist the enzyme mechanism along the catalytic cycle. Identification and characterization of these higher-energy (also called excited) sub-states and the associated populations are challenging, as these sub-states are very short-lived and therefore rarely populated. Specialized techniques based on computer simulations, theoretical modeling, and nuclear magnetic resonance have been developed for quantitative characterization of these sub-states and populations. This chapter discusses these techniques and provides examples of their applications to enzyme systems.

  6. Structures of the inactive and active states of RIP2 kinase inform on the mechanism of activation.

    Directory of Open Access Journals (Sweden)

    Erika Pellegrini

    Full Text Available Innate immune receptors NOD1 and NOD2 are activated by bacterial peptidoglycans leading to recruitment of adaptor kinase RIP2, which, upon phosphorylation and ubiquitination, becomes a scaffold for downstream effectors. The kinase domain (RIP2K is a pharmaceutical target for inflammatory diseases caused by aberrant NOD2-RIP2 signalling. Although structures of active RIP2K in complex with inhibitors have been reported, the mechanism of RIP2K activation remains to be elucidated. Here we analyse RIP2K activation by combining crystal structures of the active and inactive states with mass spectrometric characterization of their phosphorylation profiles. The active state has Helix αC inwardly displaced and the phosphorylated Activation Segment (AS disordered, whilst in the inactive state Helix αC is outwardly displaced and packed against the helical, non-phosphorylated AS. Biophysical measurements show that the active state is a stable dimer whilst the inactive kinase is in a monomer-dimer equilibrium, consistent with the observed structural differences at the dimer interface. We conclude that RIP2 kinase auto-phosphorylation is intimately coupled to dimerization, similar to the case of BRAF. Our results will help drug design efforts targeting RIP2 as a potential treatment for NOD2-RIP2 related inflammatory diseases.

  7. A national survey of 'inactive' physicians in the United States of America: enticements to reentry

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    Brotherton Sarah E

    2011-02-01

    Full Text Available Abstract Background Physicians leaving and reentering clinical practice can have significant medical workforce implications. We surveyed inactive physicians younger than typical retirement age to determine their reasons for clinical inactivity and what barriers, real or perceived, there were to reentry into the medical workforce. Methods A random sample of 4975 inactive physicians aged under 65 years was drawn from the Physician Masterfile of the American Medical Association in 2008. Physicians were mailed a survey about activity in medicine and perceived barriers to reentry. Chi-square statistics were used for significance tests of the association between categorical variables and t-tests were used to test differences between means. Results Our adjusted response rate was 36.1%. Respondents were fully retired (37.5%, not currently active in medicine (43.0% or now active (reentered, 19.4%. Nearly half (49.5% were in or had practiced primary care. Personal health was the top reason for leaving for fully retired physicians (37.8% or those not currently active in medicine (37.8% and the second highest reason for physicians who had reentered (28.8%. For reentered (47.8% and inactive (51.5% physicians, the primary reason for returning or considering returning to practice was the availability of part-time work or flexible scheduling. Retired and currently inactive physicians used similar strategies to explore reentry, and 83% of both groups thought it would be difficult; among those who had reentered practice, 35.9% reported it was difficult to reenter. Retraining was uncommon for this group (37.5%. Conclusion Availability of part-time work and flexible scheduling have a strong influence on decisions to leave or reenter clinical practice. Lack of retraining before reentry raises questions about patient safety and the clinical competence of reentered physicians.

  8. Structural heterogeneity of the μ-opioid receptor’s conformational ensemble in the apo state

    Science.gov (United States)

    Sena, Diniz M.; Cong, Xiaojing; Giorgetti, Alejandro; Kless, Achim; Carloni, Paolo

    2017-04-01

    G-protein coupled receptors (GPCRs) are the largest and most pharmaceutically relevant family of membrane proteins. Here, fully unbiased, enhanced sampling simulations of a constitutively active mutant (CAM) of a class A GPCR, the μ-opioid receptor (μOR), demonstrates repeated transitions between the inactive (IS) and active-like (AS-L) states. The interconversion features typical activation/inactivation patterns involving established conformational rearrangements of conserved residues. By contrast, wild-type μOR remains in IS during the same course of simulation, consistent with the low basal activity of the protein. The simulations point to an important role of residue W2936.48 at the “toggle switch” in the mutation-induced constitutive activation. Such role has been already observed for other CAMs of class A GPCRs. We also find a significantly populated intermediate state, rather similar to IS. Based on the remarkable accord between simulations and experiments, we suggest here that this state, which has escaped so far experimental characterization, might constitute an early step in the activation process of the apo μOR CAM.

  9. The nucleotide-free state of heterotrimeric G proteins α-subunit adopts a highly stable conformation.

    Science.gov (United States)

    Andhirka, Sai Krishna; Vignesh, Ravichandran; Aradhyam, Gopala Krishna

    2017-08-01

    Deciphering the mechanism of activation of heterotrimeric G proteins by their cognate receptors continues to be an intriguing area of research. The recently solved crystal structure of the ternary complex captured the receptor-bound α-subunit in an open conformation, without bound nucleotide has improved our understanding of the activation process. Despite these advancements, the mechanism by which the receptor causes GDP release from the α-subunit remains elusive. To elucidate the mechanism of activation, we studied guanine nucleotide-induced structural stability of the α-subunit (in response to thermal/chaotrope-mediated stress). Inherent stabilities of the inactive (GDP-bound) and active (GTP-bound) forms contribute antagonistically to the difference in conformational stability whereas the GDP-bound protein is able to switch to a stable intermediate state, GTP-bound protein loses this ability. Partial perturbation of the protein fold reveals the underlying influence of the bound nucleotide providing an insight into the mechanism of activation. An extra stable, pretransition intermediate, 'empty pocket' state (conformationally active-state like) in the unfolding pathway of GDP-bound protein mimics a gating system - the activation process having to overcome this stable intermediate state. We demonstrate that a relatively more complex conformational fold of the GDP-bound protein is at the core of the gating system. We report capturing this threshold, 'metastable empty pocket' conformation (the gate) of α-subunit of G protein and hypothesize that the receptor activates the G protein by enabling it to achieve this structure through mild structural perturbation. © 2017 Federation of European Biochemical Societies.

  10. Molecular Basis of Inactive B-RAF(WT) and B-RAF(V600E) Ligand Inhibition, Selectivity and Conformational Stability: An in Silico Study

    DEFF Research Database (Denmark)

    Fratev, Filip Filipov; Jonsdottir, Svava Osk; Mihaylova, E.

    2009-01-01

    The B-RAF kinase plays an important role both in tumor induction and maintenance in several cancers. The molecular basis of the inactive B-RAF(WT) and B-RAF(V600E) inhibition and selectivity of a series of inhibitors was examined with a combination of molecular dynamics (MD), free energy MM-PBSA ...

  11. New York State's Extreme School Segregation: Inequality, Inaction and a Damaged Future

    Science.gov (United States)

    Kucsera, John

    2014-01-01

    The fight for equal educational opportunity in New York has followed a pattern similar to other diverse or racially transforming states. From the 1950s to 1980s, the issue of school desegregation was an important issue. Local civil rights pressure, the courts, and legislation attempted to desegregate large urban school systems through both…

  12. Thermal transport in chiral conformal theories and hierarchical quantum Hall states

    International Nuclear Information System (INIS)

    Cappelli, Andrea; Huerta, Marina; Zemba, Guillermo R.

    2002-01-01

    Chiral conformal field theories are characterized by a ground-state current at finite temperature, that could be observed, e.g., in the edge excitations of the quantum Hall effect. We show that the corresponding thermal conductance is directly proportional to the gravitational anomaly of the conformal theory, upon extending the well-known relation between specific heat and conformal anomaly. The thermal current could signal the elusive neutral edge modes that are expected in the hierarchical Hall states. We then compute the thermal conductance for the Abelian multi-component theory and the W 1+∞ minimal model, two conformal theories that are good candidates for describing the hierarchical states. Their conductances agree to leading order but differ in the first, universal finite-size correction, that could be used as a selective experimental signature

  13. Conformational states of N-acylalanine dithio esters: correlation of resonance Raman spectra with structures

    International Nuclear Information System (INIS)

    Lee, H.; Angus, R.H.; Storer, A.C.; Varughese, K.I.; Carey, P.R.

    1988-01-01

    The conformational states of N-acylalanine dithio esters, involving rotational isomers about the RC(=O)NH-CH(CH 3 ) and NHCH(CH 3 )-C(=S) bonds, are defined and compared to those of N-acylglycine dithio esters. The structure of N-(p-nitrobenzoyl)-DL-alanine ethyl dithio ester has been determined by X-ray crystallographic analysis; it is a B-type conformer with the amide N atom cis to the thiol sulfur. Raman and resonance Raman (RR) measurements on this compound and for the B conformers of solid N-benzoyl-DL-alanine ethyl dithio ester and N-(β-phenylpropionyl)-DL-alanine ethyl dithio ester and its NHCH(CD 3 )C(=S) and NHCH(CH 3 ) 13 C(=S) analogues are used to set up a library of RR data for alanine-based dithio esters in a B-conformer state. RR data for this solid material in its isotopically unsubstituted and CH(C-D 3 )C(=S) and CH(CH 3 ) 13 C(=S) forms provide information on the RR signatures of alanine dithio esters in A-like conformations. RR spectra are compared for the solid compounds, for N-(p-nitrobenzoyl)-DL-alanine, N-(β-phenylpropionyl)-DL-alanine, and (methyloxycarbonyl)-L-phenylalanyl-DL-alanine ethyl dithio ester, and for several 13 C=S- and CD 3 -substituted analogues in CCl 4 or aqueous solutions. The RR data demonstrate that the alanine-based dithio esters take up A, B, and C 5 conformations in solution. The RR spectra of these conformers are clearly distinguishable from those for the same conformers of N-acylglycine dithio esters. However, the crystallographic and spectroscopic results show that the results show that the conformational properties of N-acylglycine and N-acylalanine dithio esters are very similar

  14. Conformational instability of the lowest triplet state of the benzene nucleus: I. The unsubstituted molecule

    NARCIS (Netherlands)

    van der Waals, J.H.; van Hemert, M.C.; Buma, W.J.

    1990-01-01

    Experiments on benzene have established that its lowest triplet state (3B1u) is conformationally unstable owing to vibronic coupling with the next higher state (3E1u). This instability was found to be critically dependent on the influence of a crystal field. An analogous vibronic coupling is to be

  15. Probing conformational changes in rhodopsin using hydrogen-deuterium exchange coupled to mass spectrometry.

    Science.gov (United States)

    Orban, Tivadar; Tsybovsky, Yaroslav

    2015-01-01

    Hydrogen-deuterium exchange coupled to mass spectrometry is a powerful tool to evaluate changes in protein conformation between two or more states. Here, we describe a complete methodology that can be used to assess conformational changes in rhodopsin accompanying its transition from the inactive to activated state upon light exposure. This approach may be employed to investigate the structure and conformational changes of various membrane proteins.

  16. Constructing Markov State Models to elucidate the functional conformational changes of complex biomolecules

    KAUST Repository

    Wang, Wei

    2017-10-06

    The function of complex biomolecular machines relies heavily on their conformational changes. Investigating these functional conformational changes is therefore essential for understanding the corresponding biological processes and promoting bioengineering applications and rational drug design. Constructing Markov State Models (MSMs) based on large-scale molecular dynamics simulations has emerged as a powerful approach to model functional conformational changes of the biomolecular system with sufficient resolution in both time and space. However, the rapid development of theory and algorithms for constructing MSMs has made it difficult for nonexperts to understand and apply the MSM framework, necessitating a comprehensive guidance toward its theory and practical usage. In this study, we introduce the MSM theory of conformational dynamics based on the projection operator scheme. We further propose a general protocol of constructing MSM to investigate functional conformational changes, which integrates the state-of-the-art techniques for building and optimizing initial pathways, performing adaptive sampling and constructing MSMs. We anticipate this protocol to be widely applied and useful in guiding nonexperts to study the functional conformational changes of large biomolecular systems via the MSM framework. We also discuss the current limitations of MSMs and some alternative methods to alleviate them.

  17. Quantum Hall states and conformal field theory on a singular surface

    Science.gov (United States)

    Can, T.; Wiegmann, P.

    2017-12-01

    In Can et al (2016 Phys. Rev. Lett. 117), quantum Hall states on singular surfaces were shown to possess an emergent conformal symmetry. In this paper, we develop this idea further and flesh out details on the emergent conformal symmetry in holomorphic adiabatic states, which we define in the paper. We highlight the connection between the universal features of geometric transport of quantum Hall states and holomorphic dimension of primary fields in conformal field theory. In parallel we compute the universal finite-size corrections to the free energy of a critical system on a hyperbolic sphere with conical and cusp singularities, thus extending the result of Cardy and Peschel for critical systems on a flat cone (Cardy and Peschel 1988 Nucl. Phys. B 300 377–92), and the known results for critical systems on polyhedra and flat branched Riemann surfaces.

  18. Excited state conformational dynamics in carotenoids: dark intermediates and excitation energy transfer.

    Science.gov (United States)

    Beck, Warren F; Bishop, Michael M; Roscioli, Jerome D; Ghosh, Soumen; Frank, Harry A

    2015-04-15

    A consideration of the excited state potential energy surfaces of carotenoids develops a new hypothesis for the nature of the conformational motions that follow optical preparation of the S2 (1(1)Bu(+)) state. After an initial displacement from the Franck-Condon geometry along bond length alternation coordinates, it is suggested that carotenoids pass over a transition-state barrier leading to twisted conformations. This hypothesis leads to assignments for several dark intermediate states encountered in femtosecond spectroscopic studies. The Sx state is assigned to the structure reached upon the onset of torsional motions near the transition state barrier that divides planar and twisted structures on the S2 state potential energy surface. The X state, detected recently in two-dimensional electronic spectra, corresponds to a twisted structure well past the barrier and approaching the S2 state torsional minimum. Lastly, the S(∗) state is assigned to a low lying S1 state structure with intramolecular charge transfer character (ICT) and a pyramidal conformation. It follows that the bent and twisted structures of carotenoids that are found in photosynthetic light-harvesting proteins yield excited-state structures that favor the development of an ICT character and optimized energy transfer yields to (bacterio)chlorophyll acceptors. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Effects of Long-Term Acupuncture Treatment on Resting-State Brain Activity in Migraine Patients: A Randomized Controlled Trial on Active Acupoints and Inactive Acupoints

    Science.gov (United States)

    Zhao, Ling; Liu, Jixin; Zhang, Fuwen; Dong, Xilin; Peng, Yulin; Qin, Wei; Wu, Fumei; Li, Ying; Yuan, Kai; von Deneen, Karen M.; Gong, Qiyong; Tang, Zili; Liang, Fanrong

    2014-01-01

    Background Acupuncture has been commonly used for preventing migraine attacks and relieving pain during a migraine, although there is limited knowledge on the physiological mechanism behind this method. The objectives of this study were to compare the differences in brain activities evoked by active acupoints and inactive acupoints and to investigate the possible correlation between clinical variables and brain responses. Methods and Results A randomized controlled trial and resting-state functional magnetic resonance imaging (fMRI) were conducted. A total of eighty migraineurs without aura were enrolled to receive either active acupoint acupuncture or inactive acupoint acupuncture treatment for 8 weeks, and twenty patients in each group were randomly selected for the fMRI scan at the end of baseline and at the end of treatment. The neuroimaging data indicated that long-term active acupoint therapy elicited a more extensive and remarkable cerebral response compared with acupuncture at inactive acupoints. Most of the regions were involved in the pain matrix, lateral pain system, medial pain system, default mode network, and cognitive components of pain processing. Correlation analysis showed that the decrease in the visual analogue scale (VAS) was significantly related to the increased average Regional homogeneity (ReHo) values in the anterior cingulate cortex in the two groups. Moreover, the decrease in the VAS was associated with increased average ReHo values in the insula which could be detected in the active acupoint group. Conclusions Long-term active acupoint therapy and inactive acupoint therapy have different brain activities. We postulate that acupuncture at the active acupoint might have the potential effect of regulating some disease-affected key regions and the pain circuitry for migraine, and promote establishing psychophysical pain homeostasis. Trial Registration Chinese Clinical Trial Registry ChiCTR-TRC-13003635 PMID:24915066

  20. Conformational states of a bacterial α2-macroglobulin resemble those of human complement C3.

    Directory of Open Access Journals (Sweden)

    David Neves

    Full Text Available α(2 macroglobulins (α(2Ms are broad-spectrum protease inhibitors that play essential roles in the innate immune system of eukaryotic species. These large, multi-domain proteins are characterized by a broad-spectrum bait region and an internal thioester, which, upon cleavage, becomes covalently associated to the target protease, allowing its entrapment by a large conformational modification. Notably, α(2Ms are part of a larger protein superfamily that includes proteins of the complement system, such as C3, a multi-domain macromolecule which is also characterized by an internal thioester-carrying domain and whose activation represents the pivotal step in the complement cascade. Recently, α(2M/C3-like genes were identified in a large number of bacterial genomes, and the Escherichia coli α(2M homolog (ECAM was shown to be activated by proteases. In this work, we have structurally characterized ECAM by electron microscopy and small angle scattering (SAXS techniques. ECAM is an elongated, flexible molecule with overall similarities to C3 in its inactive form; activation by methylamine, chymotrypsin, or elastase induces a conformational modification reminiscent of the one undergone by the transformation of C3 into its active form, C3b. In addition, the proposed C-terminus of ECAM displays high flexibility and different conformations, and could be the recognition site for partner macromolecules. This work sheds light on a potential bacterial defense mechanism that mimics structural rearrangements essential for activation of the complement cascade in eukaryotes, and represents a possible novel target for the development of antibacterials.

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

    Science.gov (United States)

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

    2012-12-01

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

  2. Role of conformational dynamics in kinetics of an enzymatic cycle in a nonequilibrium steady state

    Science.gov (United States)

    Min, Wei; Xie, X. Sunney; Bagchi, Biman

    2009-08-01

    Enzyme is a dynamic entity with diverse time scales, ranging from picoseconds to seconds or even longer. Here we develop a rate theory for enzyme catalysis that includes conformational dynamics as cycling on a two-dimensional (2D) reaction free energy surface involving an intrinsic reaction coordinate (X) and an enzyme conformational coordinate (Q). The validity of Michaelis-Menten (MM) equation, i.e., substrate concentration dependence of enzymatic velocity, is examined under a nonequilibrium steady state. Under certain conditions, the classic MM equation holds but with generalized microscopic interpretations of kinetic parameters. However, under other conditions, our rate theory predicts either positive (sigmoidal-like) or negative (biphasic-like) kinetic cooperativity due to the modified effective 2D reaction pathway on X-Q surface, which can explain non-MM dependence previously observed on many monomeric enzymes that involve slow or hysteretic conformational transitions. Furthermore, we find that a slow conformational relaxation during product release could retain the enzyme in a favorable configuration, such that enzymatic turnover is dynamically accelerated at high substrate concentrations. The effect of such conformation retainment in a nonequilibrium steady state is evaluated.

  3. BCS wave function, matrix product states, and the Ising conformal field theory

    Science.gov (United States)

    Montes, Sebastián; Rodríguez-Laguna, Javier; Sierra, Germán

    2017-11-01

    We present a characterization of the many-body lattice wave functions obtained from the conformal blocks (CBs) of the Ising conformal field theory (CFT). The formalism is interpreted as a matrix product state using continuous ancillary degrees of freedom. We provide analytic and numerical evidence that the resulting states can be written as BCS states. We give a complete proof that the translationally invariant 1D configurations have a BCS form and we find suitable parent Hamiltonians. In particular, we prove that the ground state of the finite-size critical Ising transverse field (ITF) Hamiltonian can be obtained with this construction. Finally, we study 2D configurations using an operator product expansion (OPE) approximation. We associate these states to the weak pairing phase of the p +i p superconductor via the scaling of the pairing function and the entanglement spectrum.

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

    International Nuclear Information System (INIS)

    Lin, T.

    2012-01-01

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

  5. Barren diets increase wakeful inactivity in calves

    NARCIS (Netherlands)

    Webb, Laura E.; Engel, Bas; Reenen, van Kees; Bokkers, Eddie A.M.

    2017-01-01

    Inactivity is a vastly understudied behavioural category, which may reflect positive or negative affective states in captive or domesticated animals. Increased inactivity in barren-housed animals, in combination with an increased or decreased interest in stimuli, e.g. novel objects, can indicate

  6. Designing molecular dynamics simulations to shift populations of the conformational states of calmodulin.

    Directory of Open Access Journals (Sweden)

    Ayse Ozlem Aykut

    Full Text Available We elucidate the mechanisms that lead to population shifts in the conformational states of calcium-loaded calmodulin (Ca(2+-CaM. We design extensive molecular dynamics simulations to classify the effects that are responsible for adopting occupied conformations available in the ensemble of NMR structures. Electrostatic interactions amongst the different regions of the protein and with its vicinal water are herein mediated by lowering the ionic strength or the pH. Amino acid E31, which is one of the few charged residues whose ionization state is highly sensitive to pH differences in the physiological range, proves to be distinctive in its control of population shifts. E31A mutation at low ionic strength results in a distinct change from an extended to a compact Ca(2+-CaM conformation within tens of nanoseconds, that otherwise occur on the time scales of microseconds. The kinked linker found in this particular compact form is observed in many of the target-bound forms of Ca(2+-CaM, increasing the binding affinity. This mutation is unique in controlling C-lobe dynamics by affecting the fluctuations between the EF-hand motif helices. We also monitor the effect of the ionic strength on the conformational multiplicity of Ca(2+-CaM. By lowering the ionic strength, the tendency of nonspecific anions in water to accumulate near the protein surface increases, especially in the vicinity of the linker. The change in the distribution of ions in the vicinal layer of water allows N- and C- lobes to span a wide variety of relative orientations that are otherwise not observed at physiological ionic strength. E31 protonation restores the conformations associated with physiological environmental conditions even at low ionic strength.

  7. Interplay between singlet and triplet excited states in a conformationally locked donor–acceptor dyad

    KAUST Repository

    Filatov, Mikhail A.

    2015-10-13

    The synthesis and photophysical characterization of a palladium(II) porphyrin – anthracene dyad bridged via short and conformationally rigid bicyclo[2.2.2]octadiene spacer were achieved. A spectroscopic investigation of the prepared molecule in solution has been undertaken to study electronic energy transfer in excited singlet and triplet states between the anthracene and porphyrin units. By using steady-state and time-resolved photoluminescence spectroscopy it was shown that excitation of the singlet excited state of the anthracene leads to energy transfer to the lower-lying singlet state of porphyrin. Alternatively, excitation of the porphyrin followed by intersystem crossing to the triplet state leads to very fast energy transfer to the triplet state of anthracene. The rate of this energy transfer has been determined by transient absorption spectroscopy. Comparative studies of the dynamics of triplet excited states of the dyad and reference palladium octaethylporphyrin (PdOEP) have been performed.

  8. Flavin redox state triggers conformational changes in the PutA protein from Escherichia coli.

    Science.gov (United States)

    Zhu, Weidong; Becker, Donald F

    2003-05-13

    The regulation of proline utilization in Escherichia coli involves the proline-dependent translocation of the PutA flavoprotein from the cytoplasm to a peripheral position on the membrane. In the cytoplasm, PutA represses transcription of the proline utilization (put) genes while membrane-bound PutA catalyzes the oxidation of L-proline to glutamate. The mechanism by which PutA switches from a DNA-binding protein to a membrane-bound enzyme involves a proline-induced conformational change that is characterized by the appearance of a 119-kDa fragment during limited proteolysis of proline-reduced PutA. To establish whether the FAD redox state is responsible for the proline-induced conformational change in PutA, we distinguished the effects that FAD reduction and proline analogue binding have on PutA conformation by limited chymotrypsin proteolysis. Controlled potentiometric proteolysis of PutA demonstrated that the formation of the 119-kDa band occurs at an E(m)(conf) value of -0.058 V (pH 7.5), which is within 20 mV of the E(m) value for FAD bound to PutA. The manipulation of the E(m)(conf) value by reconstitution of PutA with the FAD analogue, 5-deazaFAD, confirmed that the conformational change observed in the presence of proline is solely dependent on the FAD redox state. The proline analogue, L-tetrahydro-2-furoic acid (L-THFA), failed to elicit the formation of the 119-kDa fragment during chymotrypsin cleavage of PutA. Instead, a unique fragment of about 93-kDa was observed, indicating that a distinct PutA conformer is stabilized by L-THFA. Reduction of L-THFA-complexed PutA, however, regenerated the 119-kDa fragment showing that reduction of the FAD cofactor overrides conformational changes induced by L-THFA. Mapping of the protease susceptibility sites in PutA revealed that the conformational changes caused by FAD reduction and L-THFA binding are transmitted to domains outside the proline dehydrogenase active site.

  9. A dualistic conformational response to substrate binding in the human serotonin transporter reveals a high affinity state for serotonin

    DEFF Research Database (Denmark)

    Bjerregaard, Henriette; Severinsen, Kasper; Said, Saida

    2015-01-01

    Serotonergic neurotransmission is modulated by the membrane-embedded serotonin transporter (SERT). SERT mediates the reuptake of serotonin into the presynaptic neurons. Conformational changes in SERT occur upon binding of ions and substrate and are crucial for translocation of serotonin across...... that were sensitized to detect a more outward-facing conformation of SERT. We found a novel high affinity outward-facing conformational state of the human SERT induced by serotonin. The ionic requirements for this new conformational response to serotonin mirror the ionic requirements for translocation...

  10. Conformal superfields and BPS states in $AdS_{4/7}$ geometries

    CERN Document Server

    Ferrara, Sergio; Ferrara, Sergio; Sokatchev, Emery

    2000-01-01

    We carry out a general analysis of the representations of the superconformal algebras OSp(8/4,R) and OSp(8*/2N) in terms of harmonic superspace. We present a construction of their highest-weight UIR's by multiplication of the different types of massless conformal superfields ("supersingletons"). Particular attention is paid to the so-called "short multiplets". Representations undergoing shortening have "protected dimension" and may correspond to BPS states in the dual supergravity theory in anti-de Sitter space. These results are relevant for the classification of multitrace operators in boundary conformally invariant theories as well as for the classification of AdS black holes preserving different fractions of supersymmetry.

  11. Natural abundant solid state NMR studies in designed tripeptides for differentiation of multiple conformers.

    Science.gov (United States)

    Jayanthi, S; Chatterjee, Bhaswati; Raghothama, S

    2009-10-01

    Solid state NMR (SSNMR) experiments on heteronuclei in natural abundance are described for three synthetically designed tripeptides Piv-(L)Pro-(L)Pro-(L)Phe-OMe (1), Piv-(D)Pro-(L)Pro-(L)Phe-OMe (2), and Piv-(D)Pro-(L)Pro-(L)Phe-NHMe (3). These peptides exist in different conformation as shown by solution state NMR and single crystal X-ray analysis (Chatterjee et al., Chem Eur J 2008, 14, 6192). In this study, SSNMR has been used to probe the conformations of these peptides in their powder form. The (13)C spectrum of peptide (1) showed doubling of resonances corresponding to cis/cis form, unlike in solution where the similar doubling is attributed to cis/trans form. This has been confirmed by the chemical shift differences of C(beta) and C(gamma) carbon of Proline in peptide (1) both in solution and SSNMR. Peptide (2) and (3) provided single set of resonances which represented all trans form across the di-Proline segment. The results are in agreement with the X-ray analysis. Solid state (15)N resonances, especially from Proline residues provided additional information, which is normally not observable in solution state NMR. (1)H chemical shifts are also obtained from a two-dimensional heteronuclear correlation experiment between (1)H--(13)C. The results confirm the utility of NMR as a useful tool for identifying different conformers in peptides in the solid state. (c) 2009 Wiley Periodicals, Inc. Biopolymers 91: 851-860, 2009.

  12. Conformational Toggling of Yeast Iso-1-Cytochrome c in the Oxidized and Reduced States

    Science.gov (United States)

    Yang, Zhongzheng; Zhu, Jing; Ying, Tianlei; Jiang, Xianwang; Zhang, Xu; Wu, Houming; Liu, Maili; Tan, Xiangshi; Cao, Chunyang; Huang, Zhong-Xian

    2011-01-01

    To convert cyt c into a peroxidase-like metalloenzyme, the P71H mutant was designed to introduce a distal histidine. Unexpectedly, its peroxidase activity was found even lower than that of the native, and that the axial ligation of heme iron was changed to His71/His18 in the oxidized state, while to Met80/His18 in the reduced state, characterized by UV-visible, circular dichroism, and resonance Raman spectroscopy. To further probe the functional importance of Pro71 in oxidation state dependent conformational changes occurred in cyt c, the solution structures of P71H mutant in both oxidation states were determined. The structures indicate that the half molecule of cyt c (aa 50–102) presents a kind of “zigzag riveting ruler” structure, residues at certain positions of this region such as Pro71, Lys73 can move a big distance by altering the tertiary structure while maintaining the secondary structures. This finding provides a molecular insight into conformational toggling in different oxidation states of cyt c that is principle significance to its biological functions in electron transfer and apoptosis. Structural analysis also reveals that Pro71 functions as a key hydrophobic patch in the folding of the polypeptide of the region (aa 50–102), to prevent heme pocket from the solvent. PMID:22087268

  13. Conformational toggling of yeast iso-1-cytochrome C in the oxidized and reduced states.

    Science.gov (United States)

    Lan, Wenxian; Wang, Zhonghua; Yang, Zhongzheng; Zhu, Jing; Ying, Tianlei; Jiang, Xianwang; Zhang, Xu; Wu, Houming; Liu, Maili; Tan, Xiangshi; Cao, Chunyang; Huang, Zhong-Xian

    2011-01-01

    To convert cyt c into a peroxidase-like metalloenzyme, the P71H mutant was designed to introduce a distal histidine. Unexpectedly, its peroxidase activity was found even lower than that of the native, and that the axial ligation of heme iron was changed to His71/His18 in the oxidized state, while to Met80/His18 in the reduced state, characterized by UV-visible, circular dichroism, and resonance Raman spectroscopy. To further probe the functional importance of Pro71 in oxidation state dependent conformational changes occurred in cyt c, the solution structures of P71H mutant in both oxidation states were determined. The structures indicate that the half molecule of cyt c (aa 50-102) presents a kind of "zigzag riveting ruler" structure, residues at certain positions of this region such as Pro71, Lys73 can move a big distance by altering the tertiary structure while maintaining the secondary structures. This finding provides a molecular insight into conformational toggling in different oxidation states of cyt c that is principle significance to its biological functions in electron transfer and apoptosis. Structural analysis also reveals that Pro71 functions as a key hydrophobic patch in the folding of the polypeptide of the region (aa 50-102), to prevent heme pocket from the solvent.

  14. Conformational toggling of yeast iso-1-cytochrome C in the oxidized and reduced states.

    Directory of Open Access Journals (Sweden)

    Wenxian Lan

    Full Text Available To convert cyt c into a peroxidase-like metalloenzyme, the P71H mutant was designed to introduce a distal histidine. Unexpectedly, its peroxidase activity was found even lower than that of the native, and that the axial ligation of heme iron was changed to His71/His18 in the oxidized state, while to Met80/His18 in the reduced state, characterized by UV-visible, circular dichroism, and resonance Raman spectroscopy. To further probe the functional importance of Pro71 in oxidation state dependent conformational changes occurred in cyt c, the solution structures of P71H mutant in both oxidation states were determined. The structures indicate that the half molecule of cyt c (aa 50-102 presents a kind of "zigzag riveting ruler" structure, residues at certain positions of this region such as Pro71, Lys73 can move a big distance by altering the tertiary structure while maintaining the secondary structures. This finding provides a molecular insight into conformational toggling in different oxidation states of cyt c that is principle significance to its biological functions in electron transfer and apoptosis. Structural analysis also reveals that Pro71 functions as a key hydrophobic patch in the folding of the polypeptide of the region (aa 50-102, to prevent heme pocket from the solvent.

  15. Bulk Renormalization Group Flows and Boundary States in Conformal Field Theories

    Directory of Open Access Journals (Sweden)

    John Cardy

    2017-08-01

    Full Text Available We propose using smeared boundary states $e^{-\\tau H}|\\cal B\\rangle$ as variational approximations to the ground state of a conformal field theory deformed by relevant bulk operators. This is motivated by recent studies of quantum quenches in CFTs and of the entanglement spectrum in massive theories. It gives a simple criterion for choosing which boundary state should correspond to which combination of bulk operators, and leads to a rudimentary phase diagram of the theory in the vicinity of the RG fixed point corresponding to the CFT, as well as rigorous upper bounds on the universal amplitude of the free energy. In the case of the 2d minimal models explicit formulae are available. As a side result we show that the matrix elements of bulk operators between smeared Ishibashi states are simply given by the fusion rules of the CFT.

  16. Elucidation of the conformational dynamics of multi-body systems by construction of Markov state models.

    Science.gov (United States)

    Zhu, Lizhe; Sheong, Fu Kit; Zeng, Xiangze; Huang, Xuhui

    2016-11-09

    Constructing Markov State Models (MSMs) based on short molecular dynamics simulations is a powerful computational technique to complement experiments in predicting long-time kinetics of biomolecular processes at atomic resolution. Even though the MSM approach has been widely applied to study one-body processes such as protein folding and enzyme conformational changes, the majority of biological processes, e.g. protein-ligand recognition, signal transduction, and protein aggregation, essentially involve multiple entities. Here we review the attempts at constructing MSMs for multi-body systems, point out the challenges therein and discuss recent algorithmic progresses that alleviate these challenges. In particular, we describe an automatic kinetics based partitioning method that achieves optimal definition of the conformational states in a multi-body system, and discuss a novel maximum-likelihood approach that efficiently estimates the slow uphill kinetics utilizing pre-computed equilibrium populations of all states. We expect that these new algorithms and their combinations may boost investigations of important multi-body biological processes via the efficient construction of MSMs.

  17. Blood Volume Response to Physical Activity and Inactivity

    Science.gov (United States)

    2007-07-01

    deconditioning effects of bed rest inactivity are independent of any disease state. The impor- tance of physical activity on reversing the effects of inactivity...Blood Volume Response to Physical Activity and Inactivity VICTOR A. CONVERTINO, PHD ABSTRACT: Data from both cross-sectional and longitu- dinal...studies provide compelling evidence that circulat- ing blood volume can be influenced by regular physical activity or inactivity. Expansion or contraction

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

    Science.gov (United States)

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

    2016-07-01

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

  19. A Dualistic Conformational Response to Substrate Binding in the Human Serotonin Transporter Reveals a High Affinity State for Serotonin*

    Science.gov (United States)

    Bjerregaard, Henriette; Severinsen, Kasper; Said, Saida; Wiborg, Ove; Sinning, Steffen

    2015-01-01

    Serotonergic neurotransmission is modulated by the membrane-embedded serotonin transporter (SERT). SERT mediates the reuptake of serotonin into the presynaptic neurons. Conformational changes in SERT occur upon binding of ions and substrate and are crucial for translocation of serotonin across the membrane. Our understanding of these conformational changes is mainly based on crystal structures of a bacterial homolog in various conformations, derived homology models of eukaryotic neurotransmitter transporters, and substituted cysteine accessibility method of SERT. However, the dynamic changes that occur in the human SERT upon binding of ions, the translocation of substrate, and the role of cholesterol in this interplay are not fully elucidated. Here we show that serotonin induces a dualistic conformational response in SERT. We exploited the substituted cysteine scanning method under conditions that were sensitized to detect a more outward-facing conformation of SERT. We found a novel high affinity outward-facing conformational state of the human SERT induced by serotonin. The ionic requirements for this new conformational response to serotonin mirror the ionic requirements for translocation. Furthermore, we found that membrane cholesterol plays a role in the dualistic conformational response in SERT induced by serotonin. Our results indicate the existence of a subpopulation of SERT responding differently to serotonin binding than hitherto believed and that membrane cholesterol plays a role in this subpopulation of SERT. PMID:25614630

  20. Multiple T state conformations in a fish hemoglobin. Carbon monoxide binding to hemoglobin of Thunnus thynnus.

    Science.gov (United States)

    Morris, R J; Neckameyer, W S; Gibson, Q H

    1981-05-10

    The blood of the Atlantic bluefin tuna (Thunnus thynnus) contains four hemoglobin components separable by chromatography on diethylaminoethylcellulose. These components are stable and functionally identical in their reactions with carbon monoxide. At low pH they remain in the T state even when liganded, and show two kinetic components in binding and in dissociation, with rates of 1) 1.2 microM-1 s-1 and 0.095 s-1 and 2) 0.013 microM-1 s-1 and 0.195 s-1, respectively, at pH 6, 20 degrees C, 0.1 m KPi. These components have difference spectra separated by more than 2 nm and are present in equal amounts. After CO has bound, there is a conformation change to an altered T state, in terms of the model of Monod et al. (Monod, J., Wyman, J., and Changeux, J. P. (1965) J. Mol. Biol. 12, 88-118), with a half-time of 65 s. At equilibrium, one-third of the slow kinetic component is changed into the new conformer, which binds CO at a rate of 0.14 microM-1 s-1.

  1. Understanding Female Inactivity in Malta

    Directory of Open Access Journals (Sweden)

    Rose Marie Azzopardi

    2014-12-01

    Full Text Available This empirical study is based in Malta, a small island state with the highest rate of economically inactive women in the European Union (EU. Using a random sample of 402 inactive female homemakers, the responses to a telephone survey revealed that (a this inactive group is motivated by aspects of social and economic well-being and to a lesser extent by aspects of personal and professional development; (b work hindrances include low wages, family responsibilities, and a dependency on social security contributions/benefits; (c the intention to work in the future is significantly associated with work motives, work hindrances, and demographic variables, resulting in an overall holdout accuracy of 84.8%; and (d the respondents would be encouraged to work if there are more supportive/flexible work structures available for working mothers, equal opportunities for women at the workplace, and employment opportunities through in-work benefits that make work pay (particularly for those aged 40+, with limited skills and with low work intensity. The findings are discussed, and the study concludes by providing four policy recommendations aimed at addressing the present shortcomings of the Maltese labor market.

  2. Characterizing highly dynamic conformational states: The transcription bubble in RNAP-promoter open complex as an example

    Science.gov (United States)

    Lerner, Eitan; Ingargiola, Antonino; Weiss, Shimon

    2018-03-01

    Bio-macromolecules carry out complicated functions through structural changes. To understand their mechanism of action, the structure of each step has to be characterized. While classical structural biology techniques allow the characterization of a few "structural snapshots" along the enzymatic cycle (usually of stable conformations), they do not cover all (and often fast interconverting) structures in the ensemble, where each may play an important functional role. Recently, several groups have demonstrated that structures of different conformations in solution could be solved by measuring multiple distances between different pairs of residues using single-molecule Förster resonance energy transfer (smFRET) and using them as constrains for hybrid/integrative structural modeling. However, this approach is limited in cases where the conformational dynamics is faster than the technique's temporal resolution. In this study, we combine existing tools that elucidate sub-millisecond conformational dynamics together with hybrid/integrative structural modeling to study the conformational states of the transcription bubble in the bacterial RNA polymerase-promoter open complex (RPo). We measured microsecond alternating laser excitation-smFRET of differently labeled lacCONS promoter dsDNA constructs. We used a combination of burst variance analysis, photon-by-photon hidden Markov modeling, and the FRET-restrained positioning and screening approach to identify two conformational states for RPo. The experimentally derived distances of one conformational state match the known crystal structure of bacterial RPo. The experimentally derived distances of the other conformational state have characteristics of a scrunched RPo. These findings support the hypothesis that sub-millisecond dynamics in the transcription bubble are responsible for transcription start site selection.

  3. Helical Propensity Affects the Conformational Properties of the Denatured State of Cytochrome c'.

    Science.gov (United States)

    Danielson, Travis A; Bowler, Bruce E

    2018-01-23

    Changing the helical propensity of a polypeptide sequence might be expected to affect the conformational properties of the denatured state of a protein. To test this hypothesis, alanines at positions 83 and 87 near the center of helix 3 of cytochrome c' from Rhodopseudomonas palustris were mutated to serine to decrease the stability of this helix. A set of 13 single histidine variants in the A83S/A87S background were prepared to permit assessment of the conformational properties of the denatured state using histidine-loop formation in 3 M guanidine hydrochloride. The data are compared with previous histidine-heme loop formation data for wild-type cytochrome c'. As expected, destabilization of helix 3 decreases the global stabilities of the histidine variants in the A83S/A87S background relative to the wild-type background. Loop stability versus loop size data yields a scaling exponent of 2.1 ± 0.2, similar to the value of 2.3 ± 0.2 obtained for wild-type cytochrome c'. However, the stabilities of all histidine-heme loops, which contain the helix 3 sequence segment, are increased in the A83S/A87S background compared to the wild-type background. Rate constants for histidine-heme loop breakage are similar for the wild-type and A83S/A87S variants. However, for histidine-heme loops that contain the helix 3 sequence segment, the rate constants for loop formation increase in the A83S/A87S background compared to the wild-type background. Thus, residual helical structure appears to stiffen the polypeptide chain slowing loop formation in the denatured state. The implications of these results for protein folding mechanisms are discussed. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  4. Solid-state nuclear magnetic resonance analysis of the conformation of an inhibitor bound to thermolysin.

    Science.gov (United States)

    Beusen, D D; McDowell, L M; Slomczynska, U; Schaefer, J

    1995-07-07

    A number of structural experimental methods are available to determine the receptor-bound conformation of ligands as part of the process of rational drug design, including X-ray diffraction and solution-state NMR. Not all receptor/ligand systems are amenable to these types of analyses due to difficulties in sample preparation or inherent limitations of the methods. Rotational echo double-resonance (REDOR) NMR is a solid-state, magic angle-spinning technique that measures the dipolar coupling between specifically labeled nuclei and enables the determination of internuclear distance. In previous studies of helical peptides, we have verified the ability of REDOR NMR to measure distances accurately and precisely. In this study we use REDOR and double REDOR to measure distances between backbone atoms in a phosphonamidate transition-state inhibitor bound to thermolysin. The 31P-13C', 31P-15N, and 31P-13C alpha distances (3.61 +/- 0.10, 3.89 +/- 0.12, and 5.37 +/- 0.13 A, respectively) measured in a complex of Cbz-GlyP-[1-13C]Leu-[15N,2-13C]Ala and the enzyme are consistent with those observed by X-ray diffraction in other comparable thermolysin/inhibitor complexes (average values of 3.58 +/- 0.04, 3.91 +/- 0.13, and 5.17 +/- 0.18 A, respectively). These results demonstrate that REDOR NMR is a viable alternative to more traditional methods such as X-ray diffraction, transferred NOESY, and isotope-edited NOESY for characterizing the receptor-bound conformation of ligands.

  5. 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...... 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...

  6. Spectroscopic Diagnosis of Excited-State Aromaticity: Capturing Electronic Structures and Conformations upon Aromaticity Reversal.

    Science.gov (United States)

    Oh, Juwon; Sung, Young Mo; Hong, Yongseok; Kim, Dongho

    2018-03-06

    scrutinize this intriguing and challenging scientific issue, expanded porphyrins have been utilized as the ideal testing platform for investigating aromaticity because they show distinct aromatic and antiaromatic characters with aromaticity-specific spectroscopic features. Expanded porphyrins exhibit perfect aromatic and antiaromatic congener pairs having the same molecular framework but different numbers of π electrons, which facilitates the study of the pure effect of aromaticity by comparative analyses. On the basis of the characteristics of expanded porphyrins, time-resolved electronic and vibrational absorption spectroscopies capture the changes in electronic structure and molecular conformations driven by the change in aromaticity and provide clear evidence for aromaticity reversal in the excited states. The approaches described in this Account pave the way for the development of new and alternative experimental indices for the evaluation of excited-state aromaticity, which will enable overarching and fundamental comprehension of the role of (anti)aromaticity in the stability, dynamics, and reactivity in the excited states with possible implications for practical applications.

  7. Changes in the Conformational State of Hemoglobin in Hemodialysed Patients with Chronic Renal Failure

    Science.gov (United States)

    Pieniazek, Anna; Gwozdzinski, Krzysztof

    2015-01-01

    The aim of this study was to evaluate the properties of internal components of erythrocytes in chronic renal failure (CRF) patients undergoing hemodialysis (HD) in comparison to control subjects. For investigation of conformational state of hemoglobin and nonheme proteins (NHP) the maleimide spin label (MSL) in electron paramagnetic resonance (EPR) was applied. The studies were performed using MSL in whole cells and hemolysate as well as proteins separated by ion exchange chromatography and checked by electrophoresis. Additionally the level of –SH groups in hemolysate and isolated internal proteins of CRF erythrocytes was determined using 4,4′-dithiodipyridine. All measurements were performed before and after hemodialysis. Oxidative stress accompanying CRF/hemodialysed patients caused a significant decrease in the mobility of internal components inside erythrocytes indicated by MSL (P hemoglobins and internal nonheme proteins in erythrocytes of CRF patients. PMID:25866600

  8. 2D fractional supersymmetry for rational conformal field theory: application for third-integer spin states

    International Nuclear Information System (INIS)

    Perez, A.; Simon, P.

    1996-01-01

    A 2D fractional supersymmetry theory is algebraically constructed. The Lagrangian is derived using an adapted superspace including, in addition to a scalar field, two fields with spins 1/3,2/3. This theory turns out to be a rational conformal field theory. The symmetry of this model goes beyond the super-Virasoro algebra and connects these third-integer spin states. Besides the stress-momentum tensor, we obtain a supercurrent of spin 4/3. Cubic relations are involved in order to close the algebra; the basic algebra is no longer a Lie or a super-Lie algebra. The central charge of this model is found to be 5/3. Finally, we analyze the form that a local invariant action should take. (orig.)

  9. Steady-state brain glucose transport kinetics re-evaluated with a four-state conformational model

    Directory of Open Access Journals (Sweden)

    João M N Duarte

    2009-10-01

    Full Text Available Glucose supply from blood to brain occurs through facilitative transporter proteins. A near linear relation between brain and plasma glucose has been experimentally determined and described by a reversible model of enzyme kinetics. A conformational four-state exchange model accounting for trans-acceleration and asymmetry of the carrier was included in a recently developed multi-compartmental model of glucose transport. Based on this model, we demonstrate that brain glucose (Gbrain as function of plasma glucose (Gplasma can be described by a single analytical equation namely comprising three kinetic compartments: blood, endothelial cells and brain. Transport was described by four parameters: apparent half saturation constant Kt, apparent maximum rate constant Tmax, glucose consumption rate CMRglc, and the iso-inhibition constant Kii that suggests Gbrain as inhibitor of the isomerisation of the unloaded carrier. Previous published data, where Gbrain was quantified as a function of plasma glucose by either biochemical methods or NMR spectroscopy, were used to determine the aforementioned kinetic parameters. Glucose transport was characterized by Kt ranging from 1.5 to 3.5 mM, Tmax/CMRglc from 4.6 to 5.6, and Kii from 51 to 149 mM. It was noteworthy that Kt was on the order of a few mM, as previously determined from the reversible model. The conformational four-state exchange model of glucose transport into the brain includes both efflux and transport inhibition by Gbrain, predicting that Gbrain eventually approaches a maximum concentration. However, since Kii largely exceeds Gplasma, iso-inhibition is unlikely to be of substantial importance for plasma glucose below 25 mM. As a consequence, the reversible model can account for most experimental observations under euglycaemia and moderate cases of hypo- and hyperglycaemia.

  10. Conformational constraining of inactive and active States of a seven transmembrane receptor by metal ion site engineering in the extracellular end of transmembrane segment V

    DEFF Research Database (Denmark)

    Rosenkilde, Mette M; David, Ralf; Oerlecke, Ilka

    2006-01-01

    The extracellular part of transmembrane segment V (TM-V) is expected to be involved in the activation process of 7TM receptors, but its role is far from clear. Here, we study the highly constitutively active CXC-chemokine receptor encoded by human herpesvirus 8 (ORF74-HHV8), in which a metal ion......-fold). Zn(II) in activating concentrations (100 microM) acted as an allosteric enhancer as it increased the B(max) (7.1-fold), the potency (9.9-fold), the affinity (1.7- and 6.1-fold in competition against agonist and inverse agonist, respectively), and the efficacy (2.5-fold) of CXCL1/GROalpha....... The activating properties of Zn(II) were not due to a metal ion site between the ligand and the receptor because CXCL1/GROalpha analogs in which the putative metal-ion binding residues had been substituted-[H19A] and [H34A]-acted like wild-type CXCL1/GROalpha. Based on the complex action of Zn...

  11. PHYSICAL (INACTIVITY AND WOMEN

    Directory of Open Access Journals (Sweden)

    Nina Đukanović

    2008-08-01

    Full Text Available Physical activity simply means movement of the body that uses energy. Physical inactivity is more common among women than men. In women physical activity reduces the risk of dying from coronary heart disease and stroke and of developing high blood pressure, diabetes mellitus, reduces blood cholesterol level, helps control weight and reduce body fat, helps control and prevention osteoporosis and artritis, reduces symptoms of anxiety and depression, reduces the risk for breast cancer. From health benefits, physical activity should be moderate or vigorous and add up to at the least 30 minutes a day.

  12. Conformational plasticity of the catalytic subunit of protein kinase CK2 and its consequences for regulation and drug design

    DEFF Research Database (Denmark)

    Niefind, Karsten; Issinger, Olaf-Georg

    2010-01-01

    retract the gamma-phospho group from its functional position. In addition to this partially inactive state human CK2alpha was recently found in a fully inactive conformation. It is incompatible with ATP-binding due to a combination of a closed hinge and a collapse of the glycine-rich loop into the ATP...... plasticity of important ATP-binding elements - the interdomain hinge region and the glycine-rich loop - was discovered. In fully active CK2alpha the hinge region is open and does not anchor the ATP ribose, but alternatively it can adopt a closed conformation, form hydrogen bonds to the ribose moiety and thus...... cavity. These conformational transitions are apparently correlated with the occupation state of a remote docking site located at the interface to the non-catalytic subunit CK2beta: if CK2beta blocks this site, the fully active conformation of CK2alpha is stabilized, while the binding of certain small...

  13. Exercise Responses after Inactivity

    Science.gov (United States)

    Convertino, Victor A.

    1986-01-01

    The exercise response after bed rest inactivity is a reduction in the physical work capacity and is manifested by significant decreases in oxygen uptake. The magnitude of decrease in maximal oxygen intake V(dot)O2max is related to the duration of confinement and the pre-bed-rest level of aerobic fitness; these relationships are relatively independent of age and gender. The reduced exercise performance and V(dot)O2max following bed rest are associated with various physiological adaptations including reductions in blood volume, submaximal and maximal stroke volume, maximal cardiac output, sceletal muscle tone and strength, and aerobic enzyme capacities, as well as increases in venous compliance and submaximal and maximal heart rate. This reduction in physiological capacity can be partially restored by specific countermeasures that provide regular muscular activity or orhtostatic stress or both during the bed rest exposure. The understanding of these physiological and physical responses to exercise following bed rest inactivity has important implications for the solution to safety and health problems that arise in clinical medicine, aerospace medicine, sedentary living, and aging.

  14. Probing conformational states of glutaryl-CoA dehydrogenase by fragment screening

    Energy Technology Data Exchange (ETDEWEB)

    Begley, Darren W.; Davies, Douglas R.; Hartley, Robert C.; Hewitt, Stephen N.; Rychel, Amanda L.; Myler, Peter J.; Van Voorhis, Wesley C.; Staker, Bart L.; Stewart, Lance J. (Emerald)

    2014-10-02

    Glutaric acidemia type 1 is an inherited metabolic disorder which can cause macrocephaly, muscular rigidity, spastic paralysis and other progressive movement disorders in humans. The defects in glutaryl-CoA dehydrogenase (GCDH) associated with this disease are thought to increase holoenzyme instability and reduce cofactor binding. Here, the first structural analysis of a GCDH enzyme in the absence of the cofactor flavin adenine dinucleotide (FAD) is reported. The apo structure of GCDH from Burkholderia pseudomallei reveals a loss of secondary structure and increased disorder in the FAD-binding pocket relative to the ternary complex of the highly homologous human GCDH. After conducting a fragment-based screen, four small molecules were identified which bind to GCDH from B. pseudomallei. Complex structures were determined for these fragments, which cause backbone and side-chain perturbations to key active-site residues. Structural insights from this investigation highlight differences from apo GCDH and the utility of small-molecular fragments as chemical probes for capturing alternative conformational states of preformed protein crystals.

  15. Changes in the Conformational State of Hemoglobin in Hemodialysed Patients with Chronic Renal Failure

    Directory of Open Access Journals (Sweden)

    Anna Pieniazek

    2015-01-01

    Full Text Available The aim of this study was to evaluate the properties of internal components of erythrocytes in chronic renal failure (CRF patients undergoing hemodialysis (HD in comparison to control subjects. For investigation of conformational state of hemoglobin and nonheme proteins (NHP the maleimide spin label (MSL in electron paramagnetic resonance (EPR was applied. The studies were performed using MSL in whole cells and hemolysate as well as proteins separated by ion exchange chromatography and checked by electrophoresis. Additionally the level of –SH groups in hemolysate and isolated internal proteins of CRF erythrocytes was determined using 4,4′-dithiodipyridine. All measurements were performed before and after hemodialysis. Oxidative stress accompanying CRF/hemodialysed patients caused a significant decrease in the mobility of internal components inside erythrocytes indicated by MSL (P < 0.02. The significant decrease in mobility of spin labeled HbA1c and HbA both before and after HD (P < 0.0002 as well as in nonheme proteins before hemodialysis (P < 0.05 versus control was indicated. Decrease in mobility of internal components of erythrocytes was accompanied by loss of thiols before and after hemodialysis versus control in NHP (P < 0.05, HbA1c (P < 0.0002, and HbA (P < 0.0005. These findings showed oxidative influence of hemodialysis on hemoglobins and internal nonheme proteins in erythrocytes of CRF patients.

  16. ATP and MO25α Regulate the Conformational State of the STRADα Pseudokinase and Activation of the LKB1 Tumour Suppressor

    Science.gov (United States)

    Zeqiraj, Elton; Filippi, Beatrice Maria; Goldie, Simon; Navratilova, Iva; Boudeau, Jérôme; Deak, Maria; Alessi, Dario R.; van Aalten, Daan M. F.

    2009-01-01

    Pseudokinases lack essential residues for kinase activity, yet are emerging as important regulators of signal transduction networks. The pseudokinase STRAD activates the LKB1 tumour suppressor by forming a heterotrimeric complex with LKB1 and the scaffolding protein MO25. Here, we describe the structure of STRADα in complex with MO25α. The structure reveals an intricate web of interactions between STRADα and MO25α involving the αC-helix of STRADα, reminiscent of the mechanism by which CDK2 interacts with cyclin A. Surprisingly, STRADα binds ATP and displays a closed conformation and an ordered activation loop, typical of active protein kinases. Inactivity is accounted for by nonconservative substitution of almost all essential catalytic residues. We demonstrate that binding of ATP enhances the affinity of STRADα for MO25α, and conversely, binding of MO25α promotes interaction of STRADα with ATP. Mutagenesis studies reveal that association of STRADα with either ATP or MO25α is essential for LKB1 activation. We conclude that ATP and MO25α cooperate to maintain STRADα in an “active” closed conformation required for LKB1 activation. It has recently been demonstrated that a mutation in human STRADα that truncates a C-terminal region of the pseudokinase domain leads to the polyhydramnios, megalencephaly, symptomatic epilepsy (PMSE) syndrome. We demonstrate this mutation destabilizes STRADα and prevents association with LKB1. In summary, our findings describe one of the first structures of a genuinely inactive pseudokinase. The ability of STRADα to activate LKB1 is dependent on a closed “active” conformation, aided by ATP and MO25α binding. Thus, the function of STRADα is mediated through an active kinase conformation rather than kinase activity. It is possible that other pseudokinases exert their function through nucleotide binding and active conformations. PMID:19513107

  17. ATP and MO25alpha regulate the conformational state of the STRADalpha pseudokinase and activation of the LKB1 tumour suppressor.

    Science.gov (United States)

    Zeqiraj, Elton; Filippi, Beatrice Maria; Goldie, Simon; Navratilova, Iva; Boudeau, Jérôme; Deak, Maria; Alessi, Dario R; van Aalten, Daan M F

    2009-06-09

    Pseudokinases lack essential residues for kinase activity, yet are emerging as important regulators of signal transduction networks. The pseudokinase STRAD activates the LKB1 tumour suppressor by forming a heterotrimeric complex with LKB1 and the scaffolding protein MO25. Here, we describe the structure of STRADalpha in complex with MO25alpha. The structure reveals an intricate web of interactions between STRADalpha and MO25alpha involving the alphaC-helix of STRADalpha, reminiscent of the mechanism by which CDK2 interacts with cyclin A. Surprisingly, STRADalpha binds ATP and displays a closed conformation and an ordered activation loop, typical of active protein kinases. Inactivity is accounted for by nonconservative substitution of almost all essential catalytic residues. We demonstrate that binding of ATP enhances the affinity of STRADalpha for MO25alpha, and conversely, binding of MO25alpha promotes interaction of STRADalpha with ATP. Mutagenesis studies reveal that association of STRADalpha with either ATP or MO25alpha is essential for LKB1 activation. We conclude that ATP and MO25alpha cooperate to maintain STRADalpha in an "active" closed conformation required for LKB1 activation. It has recently been demonstrated that a mutation in human STRADalpha that truncates a C-terminal region of the pseudokinase domain leads to the polyhydramnios, megalencephaly, symptomatic epilepsy (PMSE) syndrome. We demonstrate this mutation destabilizes STRADalpha and prevents association with LKB1. In summary, our findings describe one of the first structures of a genuinely inactive pseudokinase. The ability of STRADalpha to activate LKB1 is dependent on a closed "active" conformation, aided by ATP and MO25alpha binding. Thus, the function of STRADalpha is mediated through an active kinase conformation rather than kinase activity. It is possible that other pseudokinases exert their function through nucleotide binding and active conformations.

  18. ATP and MO25alpha regulate the conformational state of the STRADalpha pseudokinase and activation of the LKB1 tumour suppressor.

    Directory of Open Access Journals (Sweden)

    Elton Zeqiraj

    2009-06-01

    Full Text Available Pseudokinases lack essential residues for kinase activity, yet are emerging as important regulators of signal transduction networks. The pseudokinase STRAD activates the LKB1 tumour suppressor by forming a heterotrimeric complex with LKB1 and the scaffolding protein MO25. Here, we describe the structure of STRADalpha in complex with MO25alpha. The structure reveals an intricate web of interactions between STRADalpha and MO25alpha involving the alphaC-helix of STRADalpha, reminiscent of the mechanism by which CDK2 interacts with cyclin A. Surprisingly, STRADalpha binds ATP and displays a closed conformation and an ordered activation loop, typical of active protein kinases. Inactivity is accounted for by nonconservative substitution of almost all essential catalytic residues. We demonstrate that binding of ATP enhances the affinity of STRADalpha for MO25alpha, and conversely, binding of MO25alpha promotes interaction of STRADalpha with ATP. Mutagenesis studies reveal that association of STRADalpha with either ATP or MO25alpha is essential for LKB1 activation. We conclude that ATP and MO25alpha cooperate to maintain STRADalpha in an "active" closed conformation required for LKB1 activation. It has recently been demonstrated that a mutation in human STRADalpha that truncates a C-terminal region of the pseudokinase domain leads to the polyhydramnios, megalencephaly, symptomatic epilepsy (PMSE syndrome. We demonstrate this mutation destabilizes STRADalpha and prevents association with LKB1. In summary, our findings describe one of the first structures of a genuinely inactive pseudokinase. The ability of STRADalpha to activate LKB1 is dependent on a closed "active" conformation, aided by ATP and MO25alpha binding. Thus, the function of STRADalpha is mediated through an active kinase conformation rather than kinase activity. It is possible that other pseudokinases exert their function through nucleotide binding and active conformations.

  19. Susceptibility of β1 Na+-K+ pump subunit to glutathionylation and oxidative inhibition depends on conformational state of pump.

    Science.gov (United States)

    Liu, Chia-Chi; Garcia, Alvaro; Mahmmoud, Yasser A; Hamilton, Elisha J; Galougahi, Keyvan Karimi; Fry, Natasha A S; Figtree, Gemma A; Cornelius, Flemming; Clarke, Ronald J; Rasmussen, Helge H

    2012-04-06

    Glutathionylation of cysteine 46 of the β1 subunit of the Na(+)-K(+) pump causes pump inhibition. However, the crystal structure, known in a state analogous to an E2·2K(+)·P(i) configuration, indicates that the side chain of cysteine 46 is exposed to the lipid bulk phase of the membrane and not expected to be accessible to the cytosolic glutathione. We have examined whether glutathionylation depends on the conformational changes in the Na(+)-K(+) pump cycle as described by the Albers-Post scheme. We measured β1 subunit glutathionylation and function of Na(+)-K(+)-ATPase in membrane fragments and in ventricular myocytes. Signals for glutathionylation in Na(+)-K(+)-ATPase-enriched membrane fragments suspended in solutions that preferentially induce E1ATP and E1Na(3) conformations were much larger than signals in solutions that induce the E2 conformation. Ouabain further reduced glutathionylation in E2 and eliminated an increase seen with exposure to the oxidant peroxynitrite (ONOO(-)). Inhibition of Na(+)-K(+)-ATPase activity after exposure to ONOO(-) was greater when the enzyme had been in the E1Na(3) than the E2 conformation. We exposed myocytes to different extracellular K(+) concentrations to vary the membrane potential and hence voltage-dependent conformational poise. K(+) concentrations expected to shift the poise toward E2 species reduced glutathionylation, and ouabain eliminated a ONOO(-)-induced increase. Angiotensin II-induced NADPH oxidase-dependent Na(+)-K(+) pump inhibition was eliminated by conditions expected to shift the poise toward the E2 species. We conclude that susceptibility of the β1 subunit to glutathionylation depends on the conformational poise of the Na(+)-K(+) pump.

  20. Susceptibility of β1 Na+-K+ Pump Subunit to Glutathionylation and Oxidative Inhibition Depends on Conformational State of Pump*

    Science.gov (United States)

    Liu, Chia-Chi; Garcia, Alvaro; Mahmmoud, Yasser A.; Hamilton, Elisha J.; Galougahi, Keyvan Karimi; Fry, Natasha A. S.; Figtree, Gemma A.; Cornelius, Flemming; Clarke, Ronald J.; Rasmussen, Helge H.

    2012-01-01

    Glutathionylation of cysteine 46 of the β1 subunit of the Na+-K+ pump causes pump inhibition. However, the crystal structure, known in a state analogous to an E2·2K+·Pi configuration, indicates that the side chain of cysteine 46 is exposed to the lipid bulk phase of the membrane and not expected to be accessible to the cytosolic glutathione. We have examined whether glutathionylation depends on the conformational changes in the Na+-K+ pump cycle as described by the Albers-Post scheme. We measured β1 subunit glutathionylation and function of Na+-K+-ATPase in membrane fragments and in ventricular myocytes. Signals for glutathionylation in Na+-K+-ATPase-enriched membrane fragments suspended in solutions that preferentially induce E1ATP and E1Na3 conformations were much larger than signals in solutions that induce the E2 conformation. Ouabain further reduced glutathionylation in E2 and eliminated an increase seen with exposure to the oxidant peroxynitrite (ONOO−). Inhibition of Na+-K+-ATPase activity after exposure to ONOO− was greater when the enzyme had been in the E1Na3 than the E2 conformation. We exposed myocytes to different extracellular K+ concentrations to vary the membrane potential and hence voltage-dependent conformational poise. K+ concentrations expected to shift the poise toward E2 species reduced glutathionylation, and ouabain eliminated a ONOO−-induced increase. Angiotensin II-induced NADPH oxidase-dependent Na+-K+ pump inhibition was eliminated by conditions expected to shift the poise toward the E2 species. We conclude that susceptibility of the β1 subunit to glutathionylation depends on the conformational poise of the Na+-K+ pump. PMID:22354969

  1. Application of Conformational Space Search in Drug Action | Adikwu ...

    African Journals Online (AJOL)

    ... therapeutic groups are presented. Conformational space search will lead to isolating the exact conformation with the desired medicinal properties. Many conformations of a plant isolate may exist which are active, weakly active or inactive. Key Words: Conformational, Space, Drug Action Bio-Research Vol.1(2) 2003: 69-76 ...

  2. New Perspectives for Hadron Phenomenology:The Effects of Final-State Interactions and Near-Conformal Effective QCD Couplings

    Energy Technology Data Exchange (ETDEWEB)

    Brodsky, S

    2003-10-24

    The effective QCD charge extracted from {tau} decay is remarkably constant at small momenta, implying the near-conformal behavior of hadronic interactions at small momentum transfer. The correspondence of large-N{sub c} supergravity theory in higher-dimensional anti-de Sitter spaces with gauge theory in physical space-time also has interesting implications for hadron phenomenology in the conformal limit, such as constituent counting rules for hard exclusive processes. The utility of light-front quantization and lightfront Fock wavefunctions for analyzing such phenomena and representing the dynamics of QCD bound states is reviewed. I also discuss the novel effects of initial- and final-state interactions in hard QCD inclusive processes, including Bjorken-scaling single-spin asymmetries and the leading-twist diffractive and shadowing contributions to deep inelastic lepton-proton scattering.

  3. Selection of conformational states in surface self-assembly for a molecule with eight possible pairs of surface enantiomers

    DEFF Research Database (Denmark)

    Nuermaimaiti, Ajiguli; Schultz-Falk, Vickie; Lind Cramer, Jacob

    2016-01-01

    Self-assembly of a molecule with many distinct conformational states, resulting in eight possible pairs of surface enantiomers, is investigated on a Au(111) surface under UHV conditions. The complex molecule is equipped with alkyl and carboxyl moieties to promote controlled self-assembly of lamel...... moieties in mirror-image domains of the lamellae structures, leading to selection of three out of the eight possible enantiomeric pairs....

  4. 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 vibr...

  5. Delineation of alternative conformational states in Escherichia coli peptide deformylase via thermodynamic studies for the binding of actinonin.

    Science.gov (United States)

    Berg, Alexander K; Srivastava, D K

    2009-02-24

    We investigated the binding of a naturally occurring antibiotic, actinonin, to the Ni(2+)-reconstituted recombinant form of Escherichia coli peptide deformylase (PDF(Ec)) via isothermal titration microcalorimetry. The binding data conformed to both exothermic and endothermic phases with magnitudes of DeltaG degrees , DeltaH degrees , and TDeltaS degrees being equal to -12, -2.7, and 9.3 kcal/mol and -8.7, 3.9, and 12.6 kcal/mol, respectively. Evidently, although both phases are dominated by favorable entropic changes, the exothermic phase has about 6.7 kcal/mol enthalpic advantage over the endothermic phase. We observed that the removal of bound Ni(2+) from PDF(Ec) abolished the exothermic phase without affecting the endothermic phase, but it was regained upon addition of Zn(2+). In conjunction with metal analysis data, we propose that the recombinant form of PDF(Ec) is expressed in two stable conformational states that yield markedly distinct ITC profiles (i.e., exothermic versus endothermic) upon interaction with actinonin. The existence of two conformational states of PDF(Ec) is further supported by the observation of two distinct and independent transitions during the thermal unfolding of the enzyme. In addition, the thermodynamic data reveal that the formation of the PDF(Ec)-actinonin complex results in the transfer of one H(+) from the enzyme phase to the bulk solvent at pH 6.3. Both exothermic and endothermic phases produce highly negative DeltaC(p) degrees values, but there is no apparent enthalpy-entropy compensation effect upon formation of the PDF(Ec)-actinonin complex. In view of the known structural features of the enzyme, arguments are presented that the alternative conformational states of PDF(Ec) are modulated by the metal ligation at the enzyme site.

  6. Inatividade física no lazer em trabalhadores da indústria do Rio Grande do Sul, Brasil Physical inactivity during leisure-time among industrial workers from the State of Rio Grande do Sul, Brazil

    Directory of Open Access Journals (Sweden)

    Giovâni Firpo Del Duca

    2011-03-01

    Full Text Available O estudo investigou a prevalência e os fatores associados à inatividade física no lazer em trabalhadores da indústria do Rio Grande do Sul. Empregou-se questionário para a coleta de dados, com uso da regressão de Poisson na análise. Participaram do estudo 2.265 trabalhadores, sendo a maioria homens (55,9%. Grande proporção dos trabalhadores enquadrou-se na faixa etária de até 29 anos (47,6%. A prevalência de inatividade física no lazer foi de 45,6% (IC95%: 43,5; 47,6, associando-se com: sexo feminino, ter companheiro(a, ser fumante, não estar satisfeito(a com o peso corporal e apresentar percepção negativa de bem-estar no lazer. Detectou-se associação direta do desfecho com o aumento da idade e associação inversa com a autopercepção de saúde. Conclui-se que a prevalência de inatividade física no lazer em trabalhadores foi elevada, sendo o sexo feminino e a percepção de bem-estar no lazer negativa os fatores mais fortemente associados à ocorrência de tal comportamento..The objective of this study was to investigate the prevalence and associated factors to physical inactivity during leisure-time in a representative sample of industrial workers from Rio Grande do Sul, Brazil. Physical inactivity was defined as the negative response to the question: "Do you perform any type of physical activity during leisure-time, such as exercises (calisthenics, walking, jogging, sports, dance or martial arts?" The sample included 2,265 workers, and the prevalence of physical inactivity was 45.6% (CI95%: 43.5; 47.6, which was significantly higher for females, those living with a companion, smokers, those not satisfied with their body weight, and those with a negative perception of their own leisure. Besides, it was observed a positive association of physical inactivity with age, and a negative association with self assessment of health status. Overall, results indicate that the prevalence of leisure-time physical inactivity among

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

    Directory of Open Access Journals (Sweden)

    Barry J Grant

    2009-03-01

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

  8. Applications of neural network prediction of conformational states for small peptides from spectra and of fold classes

    DEFF Research Database (Denmark)

    Bohr, Henrik; Røgen, Peter; Jalkanen, Karl J.

    2001-01-01

    . The calculations were done both with solvent atoms (up to ten water molecules) and without, and hence the neural networks could be used to monitor the influence of the solvent on hydrogen bond formation. The calculations at this stage only involved very short peptide fragments of a few alanine amino acids...... to construct vibrational spectra for each of the conformational states with low energy. From the spectra, neural networks could be trained to distinguish between the various states and thus be able to generate a larger set of relevant structures and their relation to secondary structures of the peptides...

  9. Conformational changes and metastable states induced in proteins by green light

    Science.gov (United States)

    Comorosan, Sorin; Popescu, Irinel; Polosan, Silviu; Pirvu, Cristian; Ionescu, Elena; Paslaru, Liliana; Apostol, Marian

    2015-01-01

    In this paper we report conformational changes recorded on a protein molecule (α-amylase) under green light irradiation. In order to explain the experimental results we advanced the hypothesis that green light induces electric dipoles in the protein, which interact with each other, generating conformational modifications toward a more compact design, with different physical properties. The experiments were carried out with un-polarized light (λ = 520 nm) from a light-emitting-diode (1000 lm, 20 W, 105 mW on the target). In view of the character of our hypothesis, and corroborated with all our experimental results, we suggest that this phenomenon may be more extended and general, specific for a larger class of proteins, occurring on the protein macromolecules under the green light. The effects of α-amylase protein irradiation were revealed by circular dichroism, fluorescence, Raman and FTIR-spectroscopies, zeta potential, cyclic voltammetry, electric impedance spectroscopy and atomic force microscopy. Tentatively, we term the novel conformations as P∗ (polarized) proteins.

  10. A survey on the state on the use of conformation radiotherapy units in Japan

    International Nuclear Information System (INIS)

    Tomaru, Teizo; Onai, Yoshio; Abe, Shunsuke

    1985-01-01

    A survey on the stage on the use of conformation radiotherapy units in Japan was performed by the Radiotherapy Equipments Committee of the Japanese Association for Radiotherapy Systems. The questionnaire was sent to 34 hospitals, which are all the hospitals equipped with these units, and 13 cancer and adult disease centers. The answers were collected from 42 hospitals, of which the 31 from formers and 11 from latters. In June, 1984, 27 conformation radiotherapy units (11 units with a pair of lower jaws and 16 units with multi-leaf collimators) were being used at 26 hospitals answered to questionnaire. During a month from May 16 to June 15 in 1984, conformation radiotherapy was performed at 10 hopsitals, and mean number of patients per day treated with these irradiation techniques was 3.7 +- 3.5. Fixed beam radiotherapy with irregular shape fields using multi-leaf collimators was also performed at 8 hospitals and mean number of patients per day treated with this fixed beam was 6.6 +- 3.9. Hollow-out irradiation technique was used at 4 hospitals, and 3.8 patients per day per hospital were treated with this technique. (author)

  11. The introduction of hydrogen bond and hydrophobicity effects into the rotational isomeric states model for conformational analysis of unfolded peptides

    International Nuclear Information System (INIS)

    Engin, Ozge; Sayar, Mehmet; Erman, Burak

    2009-01-01

    Relative contributions of local and non-local interactions to the unfolded conformations of peptides are examined by using the rotational isomeric states model which is a Markov model based on pairwise interactions of torsion angles. The isomeric states of a residue are well described by the Ramachandran map of backbone torsion angles. The statistical weight matrices for the states are determined by molecular dynamics simulations applied to monopeptides and dipeptides. Conformational properties of tripeptides formed from combinations of alanine, valine, tyrosine and tryptophan are investigated based on the Markov model. Comparison with molecular dynamics simulation results on these tripeptides identifies the sequence-distant long-range interactions that are missing in the Markov model. These are essentially the hydrogen bond and hydrophobic interactions that are obtained between the first and the third residue of a tripeptide. A systematic correction is proposed for incorporating these long-range interactions into the rotational isomeric states model. Preliminary results suggest that the Markov assumption can be improved significantly by renormalizing the statistical weight matrices to include the effects of the long-range correlations

  12. Conformational Analysis, Molecular Structure and Solid State Simulation of the Antiviral Drug Acyclovir (Zovirax Using Density Functional Theory Methods

    Directory of Open Access Journals (Sweden)

    Margarita Clara Alvarez-Ros

    2014-06-01

    Full Text Available The five tautomers of the drug acyclovir (ACV were determined and optimised at the MP2 and B3LYP quantum chemical levels of theory. The stability of the tautomers was correlated with different parameters. On the most stable tautomer N1 was carried out a comprehensive conformational analysis, and the whole conformational parameters (R, β, Φ, φ1, φ2, φ3, φ4, φ5 were studied as well as the NBO Natural atomic charges. The calculations were carried out with full relaxation of all geometrical parameters. The search located at least 78 stable structures within 8.5 kcal/mol electronic energy range of the global minimum, and classified in two groups according to the positive or negative value of the torsional angle j1. In the nitrogen atoms and in the O2' and O5' oxygen atoms of the most stable conformer appear a higher reactivity than in the natural nucleoside deoxyguanosine. The solid state was simulated through a dimer and tetramer forms and the structural parameters were compared with the X-ray crystal data available. Several general conclusions were emphasized.

  13. Enhancing pairwise state-transition weights: A new weighting scheme in simulated tempering that can minimize transition time between a pair of conformational states

    Science.gov (United States)

    Qiao, Qin; Zhang, Hou-Dao; Huang, Xuhui

    2016-04-01

    Simulated tempering (ST) is a widely used enhancing sampling method for Molecular Dynamics simulations. As one expanded ensemble method, ST is a combination of canonical ensembles at different temperatures and the acceptance probability of cross-temperature transitions is determined by both the temperature difference and the weights of each temperature. One popular way to obtain the weights is to adopt the free energy of each canonical ensemble, which achieves uniform sampling among temperature space. However, this uniform distribution in temperature space may not be optimal since high temperatures do not always speed up the conformational transitions of interest, as anti-Arrhenius kinetics are prevalent in protein and RNA folding. Here, we propose a new method: Enhancing Pairwise State-transition Weights (EPSW), to obtain the optimal weights by minimizing the round-trip time for transitions among different metastable states at the temperature of interest in ST. The novelty of the EPSW algorithm lies in explicitly considering the kinetics of conformation transitions when optimizing the weights of different temperatures. We further demonstrate the power of EPSW in three different systems: a simple two-temperature model, a two-dimensional model for protein folding with anti-Arrhenius kinetics, and the alanine dipeptide. The results from these three systems showed that the new algorithm can substantially accelerate the transitions between conformational states of interest in the ST expanded ensemble and further facilitate the convergence of thermodynamics compared to the widely used free energy weights. We anticipate that this algorithm is particularly useful for studying functional conformational changes of biological systems where the initial and final states are often known from structural biology experiments.

  14. Enhancing pairwise state-transition weights: A new weighting scheme in simulated tempering that can minimize transition time between a pair of conformational states

    International Nuclear Information System (INIS)

    Qiao, Qin; Zhang, Hou-Dao; Huang, Xuhui

    2016-01-01

    Simulated tempering (ST) is a widely used enhancing sampling method for Molecular Dynamics simulations. As one expanded ensemble method, ST is a combination of canonical ensembles at different temperatures and the acceptance probability of cross-temperature transitions is determined by both the temperature difference and the weights of each temperature. One popular way to obtain the weights is to adopt the free energy of each canonical ensemble, which achieves uniform sampling among temperature space. However, this uniform distribution in temperature space may not be optimal since high temperatures do not always speed up the conformational transitions of interest, as anti-Arrhenius kinetics are prevalent in protein and RNA folding. Here, we propose a new method: Enhancing Pairwise State-transition Weights (EPSW), to obtain the optimal weights by minimizing the round-trip time for transitions among different metastable states at the temperature of interest in ST. The novelty of the EPSW algorithm lies in explicitly considering the kinetics of conformation transitions when optimizing the weights of different temperatures. We further demonstrate the power of EPSW in three different systems: a simple two-temperature model, a two-dimensional model for protein folding with anti-Arrhenius kinetics, and the alanine dipeptide. The results from these three systems showed that the new algorithm can substantially accelerate the transitions between conformational states of interest in the ST expanded ensemble and further facilitate the convergence of thermodynamics compared to the widely used free energy weights. We anticipate that this algorithm is particularly useful for studying functional conformational changes of biological systems where the initial and final states are often known from structural biology experiments.

  15. Enhancing pairwise state-transition weights: A new weighting scheme in simulated tempering that can minimize transition time between a pair of conformational states

    Energy Technology Data Exchange (ETDEWEB)

    Qiao, Qin, E-mail: qqiao@ust.hk; Zhang, Hou-Dao [Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon (Hong Kong); Huang, Xuhui, E-mail: xuhuihuang@ust.hk [Department of Chemistry, Division of Biomedical Engineering, Center of Systems Biology and Human Health, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon (Hong Kong); The HKUST Shenzhen Research Institute, Shenzhen (China)

    2016-04-21

    Simulated tempering (ST) is a widely used enhancing sampling method for Molecular Dynamics simulations. As one expanded ensemble method, ST is a combination of canonical ensembles at different temperatures and the acceptance probability of cross-temperature transitions is determined by both the temperature difference and the weights of each temperature. One popular way to obtain the weights is to adopt the free energy of each canonical ensemble, which achieves uniform sampling among temperature space. However, this uniform distribution in temperature space may not be optimal since high temperatures do not always speed up the conformational transitions of interest, as anti-Arrhenius kinetics are prevalent in protein and RNA folding. Here, we propose a new method: Enhancing Pairwise State-transition Weights (EPSW), to obtain the optimal weights by minimizing the round-trip time for transitions among different metastable states at the temperature of interest in ST. The novelty of the EPSW algorithm lies in explicitly considering the kinetics of conformation transitions when optimizing the weights of different temperatures. We further demonstrate the power of EPSW in three different systems: a simple two-temperature model, a two-dimensional model for protein folding with anti-Arrhenius kinetics, and the alanine dipeptide. The results from these three systems showed that the new algorithm can substantially accelerate the transitions between conformational states of interest in the ST expanded ensemble and further facilitate the convergence of thermodynamics compared to the widely used free energy weights. We anticipate that this algorithm is particularly useful for studying functional conformational changes of biological systems where the initial and final states are often known from structural biology experiments.

  16. Solid-State Examination of Conformationally Diverse Sulfonamide Receptors Based on Bis(2-anilinoethynyl)pyridine, -Bipyridine, and -Thiophene

    Science.gov (United States)

    Berryman, Orion B.; Johnson, Charles A.; Vonnegut, Chris L.; Fajardo, Kevin A.; Zakharov, Lev N.; Johnson, Darren W.; Haley, Michael M.

    2015-01-01

    Utilizing an induced-fit model and taking advantage of rotatable acetylenic C(sp)–C(sp2) bonds, we disclose the synthesis and solid-state structures of a series of conformationally diverse bis-sulfonamide arylethynyl receptors using either pyridine, 2,2′-bipyridine, or thiophene as the core aryl group. Whereas the bipyridine and thiophene structures do not appear to bind guests in the solid state, the pyridine receptors form 2 + 2 dimers with water molecules, two halides, or one of each, depending on the protonation state of the pyridine nitrogen atom. Isolation of a related bis-sulfonimide derivative demonstrates the importance of the sulfonamide N–H hydrogen bonds in dimer formation. The pyridine receptors form monomeric structures with larger guests such as BF4− or HSO4−, where the sulfonamide arms rotate to the side opposite the pyridine N atom. PMID:26405435

  17. Solid-State Examination of Conformationally Diverse Sulfonamide Receptors Based on Bis(2-anilinoethynyl)pyridine, -Bipyridine, and -Thiophene.

    Science.gov (United States)

    Berryman, Orion B; Johnson, Charles A; Vonnegut, Chris L; Fajardo, Kevin A; Zakharov, Lev N; Johnson, Darren W; Haley, Michael M

    2015-03-04

    Utilizing an induced-fit model and taking advantage of rotatable acetylenic C(sp)-C(sp 2 ) bonds, we disclose the synthesis and solid-state structures of a series of conformationally diverse bis-sulfonamide arylethynyl receptors using either pyridine, 2,2'-bipyridine, or thiophene as the core aryl group. Whereas the bipyridine and thiophene structures do not appear to bind guests in the solid state, the pyridine receptors form 2 + 2 dimers with water molecules, two halides, or one of each, depending on the protonation state of the pyridine nitrogen atom. Isolation of a related bis-sulfonimide derivative demonstrates the importance of the sulfonamide N-H hydrogen bonds in dimer formation. The pyridine receptors form monomeric structures with larger guests such as BF 4 - or HSO 4 - , where the sulfonamide arms rotate to the side opposite the pyridine N atom.

  18. Solidarity (In)action?

    DEFF Research Database (Denmark)

    Lemberg-Pedersen, Martin

    2011-01-01

    , the outsourcing to Private Security Companies (PSCs) like Finmeccanica or the subsidising of EUROSUR-projects do not facilitate solidarity. Rather they place the largest responsibility for refugees on the world’s poorest states, and consolidate the criminalization of irregular migration. Furthermore, Dublin......This article assesses the claim that the EU secures basic rights for citizens and migrants because externalization facilitates solidarity between EU states, third countries and migrants (the EFS-argument). However, it is argued that practices like European Commission (EC)-donations to UNHCR...

  19. Solidarity (In)action?

    DEFF Research Database (Denmark)

    Lemberg-Pedersen, Martin

    2011-01-01

    This article assesses the claim that the EU secures basic rights for citizens and migrants because externalization facilitates solidarity between EU states, third countries and migrants (the EFS-argument). However, it is argued that practices like European Commission (EC)-donations to UNHCR, the ...

  20. ASIC and ENaC type sodium channels: conformational states and the structures of the ion selectivity filters.

    Science.gov (United States)

    Hanukoglu, Israel

    2017-02-01

    The acid-sensing ion channels (ASICs) and epithelial sodium channels (ENaC) are members of a superfamily of channels that play critical roles in mechanosensation, chemosensation, nociception, and regulation of blood volume and pressure. These channels look and function like a tripartite funnel that directs the flow of Na + ions into the cytoplasm via the channel pore in the membrane. The subunits that form these channels share a common structure with two transmembrane segments (TM1 and TM2) and a large extracellular part. In most vertebrates, there are five paralogous genes that code for ASICs (ASIC1-ASIC5), and four for ENaC subunits alpha, beta, gamma, and delta (α, β, γ, and δ). While ASICs can form functional channels as a homo- or heterotrimer, ENaC functions as an obligate heterotrimer composed of α-β-γ or β-γ-δ subunits. The structure of ASIC has been determined in several conformations, including desensitized and open states. This review presents a comparison of the structures of these states using easy-to-understand molecular models of the full complex, the central tunnel that includes an outer vestibule, the channel pore, and ion selectivity filter. The differences in the secondary, tertiary, and quaternary structures of the states are summarized to pinpoint the conformational changes responsible for channel opening. Results of site-directed mutagenesis studies of ENaC subunits are examined in light of ASIC1 models. Based on these comparisons, a molecular model for the selectivity filter of ENaC is built by in silico mutagenesis of an ASIC1 structure. These models suggest that Na + ions pass through the filter in a hydrated state. © 2016 Federation of European Biochemical Societies.

  1. Measuring the Conformational Distance of GPCR-related Proteins Using a Joint-based Descriptor.

    Science.gov (United States)

    Thangappan, Jayaraman; Madan, Bharat; Wu, Sangwook; Lee, Sun-Gu

    2017-11-09

    Joint-based descriptor is a new level of macroscopic descriptor for protein structure using joints of secondary structures as a basic element. Here, we propose how the joint-based descriptor can be applied to examine the conformational distances or differences of transmembrane (TM) proteins. Specifically, we performed three independent studies that measured the global and conformational distances between GPCR A family and its related structures. First, the conformational distances of GPCR A family and other 7TM proteins were evaluated. This provided the information on the distant and close families or superfamilies to GPCR A family and permitted the identification of conserved local conformations. Second, computational models of GPCR A family proteins were validated, which enabled us to estimate how much they reproduce the native conformation of GPCR A proteins at global and local conformational level. Finally, the conformational distances between active and inactive states of GPCR proteins were estimated, which identified the difference of local conformation. The proposed macroscopic joint-based approach is expected to allow us to investigate structural features, evolutionary relationships, computational models and conformational changes of TM proteins in a more simplistic manner.

  2. The pandemic of physical inactivity

    DEFF Research Database (Denmark)

    Kohl, Harold W; Craig, Cora Lynn; Lambert, Estelle Victoria

    2012-01-01

    the 1950s, promotion to improve the health of populations has lagged in relation to the available evidence and has only recently developed an identifiable infrastructure, including efforts in planning, policy, leadership and advocacy, workforce training and development, and monitoring and surveillance......Physical inactivity is the fourth leading cause of death worldwide. We summarise present global efforts to counteract this problem and point the way forward to address the pandemic of physical inactivity. Although evidence for the benefits of physical activity for health has been available since...

  3. Conformation of macrolides antibiotics bound to ribosomes as determined from transferred nuclear Overhauser effect spectroscopy

    Science.gov (United States)

    Bertho, G.; Ladam, P.; Gharbi-Benarous, J.; Delaforge, M.; Girault, J.-P.

    1998-02-01

    The ribosomal bound conformation of 14-membered-ring macrolides roxithromycin, erythromycin A and their methylated derivatives has been elucidated from study of the macrolide-ribosome interactions using transferred nuclear Overhauser effect (TRNOE). Only one specific conformation is preferred in the bound state. The bioactive macrolide antibiotics studied displayed a strong NMR response, while their inactive major metabolites displayed blank TRNOESY spectrum. TRNOE analysis established correlation between the bound state conformation of these active compounds and the major conformation (A1a) in solution. La conformation liée au ribosome des antibiotiques macrolides tels que la roxithromycine, l'érythromycine A et leurs dérivés méthylés a été déterminée en utilisant l'expérience d'effet nucléaire Overhauser transféré (TRNOE). Une seule conformation spécifique est préférée dans l'état lié. Les antibiotiques macrolides actifs étudiés donnent une bonne réponse RMN alors que leurs métabolites, qui sont inactifs, présentent un spectre TRNOESY vide. L'analyse des TRNOEs établit une corrélation entre la conformation liée de ses composés actifs et la conformation (A1a) majoritaire en solution.

  4. 77 FR 14979 - Transportation Conformity Rule Restructuring Amendments

    Science.gov (United States)

    2012-03-14

    ... conformity SIPs, see EPA's ``Guidance for Developing Transportation Conformity State Implementation Plans... January 2009 guidance entitled, ``Guidance for Developing Transportation Conformity State Implementation... Transportation Conformity Rule Restructuring Amendments AGENCY: Environmental Protection Agency (EPA). ACTION...

  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. Conformal House

    DEFF Research Database (Denmark)

    Ryttov, Thomas; Sannino, Francesco

    2010-01-01

    fixed point. As a consistency check we recover the previously investigated conformal windows bounds 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....

  7. Solid state conformations and antidopaminergic effects of remoxipride hydrochloride and a closely related salicylamide, FLA 797, in relation to dopamine receptor models.

    Science.gov (United States)

    Högberg, T; Rämsby, S; de Paulis, T; Stensland, B; Csöregh, I; Wägner, A

    1986-10-01

    The X-ray structures of two new 2,6-disubstituted benzamides, i.e., remoxipride hydrochloride monohydrate [-)-(S)-3-bromo-N-[(1-ethyl-2-pyrrolidinyl)methyl]-2,6-dimethoxybenza mide hydrochloride monohydrate) and FLA 797 [-)-(S)-3-bromo-N-[(1-ethyl-2-pyrrolidinyl)methyl]-6-methoxysalicylamide ), have been determined as well as the distribution coefficients. The difference in dopamine receptor blocking activity is discussed in terms of lipophilicity and solid state conformations of the two benzamides. The major difference between the solid state conformations lies in the orientation of the carboxamide moiety. In remoxipride the carbonyl group is oriented almost perpendicularly to the benzene ring, thus preventing the formation of a hydrogen-bonded pseudo-ring between the amide hydrogen and the methoxy group found in other types of o-methoxybenzamides. In FLA 797, however, this pseudo-ring is present in the planar conformation of the salicylamide moiety. This conformation is further stabilized by a hydrogen bond between the phenol group and the carbonyl oxygen. The side chain in remoxipride adopts an extended conformation in contrast to FLA 797, where the side chain has a folded conformation. The crystal structures are related to current topographic dopamine receptor models developed from more rigid antidopaminergic compounds. Based on these comparisons, it is suggested that benzamides having an N-ethyl-2-pyrrolidinylmethyl side chain interact with the receptor in the folded conformation. The binding affinity is thought to be further increased by the planar conformation of the salicylamide moiety present in FLA 797, which permits an efficient pi-pi stacking interaction.

  8. Conformal primaries of $OSp(8/4,R)$ and BPS states in $AdS_{4}$

    CERN Document Server

    Ferrara, Sergio; Ferrara, Sergio; Sokatchev, Emery

    2000-01-01

    We derive short UIR's of the OSp(8/4,R) superalgebra of 3d N=8 superconformalfield theories by the requirement that the highest weight states areannihilated by a subset of the super-Poincare odd generators. We then find asuperfield realization of these BPS saturated UIR's as "composite operators" ofthe two basic ultrashort "supersingleton" multiplets. These representations arethe AdS4 analogue of BPS states preserving different fractions of supersymmetryand are therefore suitable to classify perturbative and non-perturbativeexcitations of M-theory compactifications.

  9. Conformational transitions and molecular hysteresis of cytochrome c oxidase: Varying the redox state by electronic wiring

    NARCIS (Netherlands)

    Nowak, Christoph; Santonicola, M.; Schach, Denise; Zhu, Jiapeng; Gennis, Robert B.; Ferguson-Miller, Shelagh; Baurecht, Dieter; Walz, Dieter; Knoll, Wolfgang; Naumann, Renate L.

    2010-01-01

    Even though the structures of cytochrome c oxidase (CcO) from different sources have been determined by X-ray crystallography in both the reduced and oxidized redox states, information about redox-induced structure-function relationships is still very limited. In the current work, redox-dependent

  10. Myelin basic protein-reactive T cells persist in an inactive state in the bone marrow of Lewis rats that have recovered from autoimmune encephalomyelitis.

    Science.gov (United States)

    Kheradmand, Taba; Wolf, Norbert A; Swanborg, Robert H

    2009-04-30

    Lewis rats immunized with guinea pig myelin basic protein residues 68-86 develop acute experimental autoimmune encephalomyelitis and recover. The predominant T cell receptor expressed by the encephalitogenic T cells is TCRBV8S2. They persist in bone marrow many weeks after recovery. CD3 is down-regulated, but >90% express CD4. They fail to proliferate to GPMBP68-86 unless a nitric oxide synthase inhibitor is added to the cultures. Perhaps these are memory T cells that are maintained in a suppressed state in BM by a nitric oxide-dependent mechanism.

  11. Gating of Connexin Channels by transjunctional-voltage: Conformations and models of open and closed states.

    Science.gov (United States)

    Bargiello, Thaddeus A; Oh, Seunghoon; Tang, Qingxiu; Bargiello, Nicholas K; Dowd, Terry L; Kwon, Taekyung

    2018-01-01

    Voltage is an important physiologic regulator of channels formed by the connexin gene family. Connexins are unique among ion channels in that both plasma membrane inserted hemichannels (undocked hemichannels) and intercellular channels (aggregates of which form gap junctions) have important physiological roles. The hemichannel is the fundamental unit of gap junction voltage-gating. Each hemichannel displays two distinct voltage-gating mechanisms that are primarily sensitive to a voltage gradient formed along the length of the channel pore (the transjunctional voltage) rather than sensitivity to the absolute membrane potential (V m or V i-o ). These transjunctional voltage dependent processes have been termed V j - or fast-gating and loop- or slow-gating. Understanding the mechanism of voltage-gating, defined as the sequence of voltage-driven transitions that connect open and closed states, first and foremost requires atomic resolution models of the end states. Although ion channels formed by connexins were among the first to be characterized structurally by electron microscopy and x-ray diffraction in the early 1980's, subsequent progress has been slow. Much of the current understanding of the structure-function relations of connexin channels is based on two crystal structures of Cx26 gap junction channels. Refinement of crystal structure by all-atom molecular dynamics and incorporation of charge changing protein modifications has resulted in an atomic model of the open state that arguably corresponds to the physiologic open state. Obtaining validated atomic models of voltage-dependent closed states is more challenging, as there are currently no methods to solve protein structure while a stable voltage gradient is applied across the length of an oriented channel. It is widely believed that the best approach to solve the atomic structure of a voltage-gated closed ion channel is to apply different but complementary experimental and computational methods and to use

  12. Coherent states of accelerated relativistic quantum particles, vacuum radiation and the spontaneous breakdown of the conformal SU(2,2) symmetry

    Science.gov (United States)

    Calixto, M.; Pérez-Romero, E.; Aldaya, V.

    2012-06-01

    We give a quantum mechanical description of accelerated relativistic particles in the framework of coherent states (CSs) of the (3+1)-dimensional conformal group SU(2, 2), with the role of accelerations and ‘kinematical redshift’ played by special conformal transformations (SCTs) and with the role of (proper) time translations played by dilations. The accelerated ground state \\tilde{\\varphi }_0 of first quantization is a CS of the conformal group. We compute the distribution function giving the occupation number of each energy level in \\tilde{\\varphi }_0 and, with it, the partition function { Z}, mean energy { E} and entropy { S}, which resemble that of an ‘Einstein solid’. An effective temperature { T} can be assigned to this ‘accelerated ensemble’ through the thermodynamic expression d{ E}/d{ S}, which leads to a (nonlinear) relation between acceleration and temperature different from Unruh’s (linear) formula. Then we construct the corresponding conformal-SU(2, 2)-invariant second-quantized theory and its spontaneous breakdown when selecting Poincaré-invariant degenerated θ-vacua (namely, CSs of conformal zero modes). SCTs (accelerations) destabilize the Poincaré vacuum and make it radiate. This article is part of a special issue of Journal of Physics A: Mathematical and Theoretical devoted to ‘Coherent states: mathematical and physical aspects’.

  13. Ensemble refinement shows conformational flexibility in crystal structures of human complement factor D

    International Nuclear Information System (INIS)

    Forneris, Federico; Burnley, B. Tom; Gros, Piet

    2014-01-01

    Ensemble-refinement analysis of native and mutant factor D (FD) crystal structures indicates a dynamical transition in FD from a self-inhibited inactive conformation to a substrate-bound active conformation that is reminiscent of the allostery in thrombin. Comparison with previously observed dynamics in thrombin using NMR data supports the crystallographic ensembles. Human factor D (FD) is a self-inhibited thrombin-like serine proteinase that is critical for amplification of the complement immune response. FD is activated by its substrate through interactions outside the active site. The substrate-binding, or ‘exosite’, region displays a well defined and rigid conformation in FD. In contrast, remarkable flexibility is observed in thrombin and related proteinases, in which Na + and ligand binding is implied in allosteric regulation of enzymatic activity through protein dynamics. Here, ensemble refinement (ER) of FD and thrombin crystal structures is used to evaluate structure and dynamics simultaneously. A comparison with previously published NMR data for thrombin supports the ER analysis. The R202A FD variant has enhanced activity towards artificial peptides and simultaneously displays active and inactive conformations of the active site. ER revealed pronounced disorder in the exosite loops for this FD variant, reminiscent of thrombin in the absence of the stabilizing Na + ion. These data indicate that FD exhibits conformational dynamics like thrombin, but unlike in thrombin a mechanism has evolved in FD that locks the unbound native state into an ordered inactive conformation via the self-inhibitory loop. Thus, ensemble refinement of X-ray crystal structures may represent an approach alternative to spectroscopy to explore protein dynamics in atomic detail

  14. Inactive ingredient Search for Approved Drug Products

    Data.gov (United States)

    U.S. Department of Health & Human Services — According to 21 CFR 210.3(b)(8), an inactive ingredient is any component of a drug product other than the active ingredient. Only inactive ingredients in the final...

  15. Vascular adaption to physical inactivity in humans

    NARCIS (Netherlands)

    Bleeker, M.W.P.

    2006-01-01

    This thesis presents studies on vascular adaptation to physical inactivity and deconditioning. Although it is clear that physical inactivity is an important risk factor for cardiovascular disease, the underlying physiological mechanisms have not yet been elucidated. In contrast to physical

  16. Vascular adaptation to physical inactivity in humans.

    NARCIS (Netherlands)

    Bleeker, M.W.P.

    2006-01-01

    This thesis presents studies on vascular adaptation to physical inactivity and deconditioning. Although it is clear that physical inactivity is an important risk factor for cardiovascular disease, the underlying physiological mechanisms have not yet been elucidated. In contrast to physical

  17. Health Risks of an Inactive Lifestyle

    Science.gov (United States)

    ... may develop a hormonal imbalance What are the health risks of an inactive lifestyle? Having an inactive ... the more sedentary you are, the higher your health risks are. How can I get started with ...

  18. Impact of Interfacial Molecular Conformation and Aggregation State on the Energetic Landscape and Performance in Organic Photovoltaics

    KAUST Repository

    Ngongang Ndjawa, Guy Olivier

    2016-11-25

    In organic photovoltaics (OPVs) the key processes relevant to device operation such as exciton dissociation and free carriers recombination occur at the donor-acceptor (D-A) interface. OPV devices require the bulk heterojunction (BHJ) architecture to function efficiently. In these BHJs, D-A interfaces are arranged in three dimensions, which makes molecular arrangements at these interfaces ill defined and hard to characterize. In addition, molecular materials used in OPVs are inherently disordered and may exhibit variable degrees of structural order in the same BHJ. Yet, D-A molecular arrangements and structure are crucial because they shape the energy landscape and photovoltaic (PV) performance in OPVs. Studies that use well-defined model systems to look in details at the interfacial molecular structure in OPVs and link it to interfacial energy landscape and device operation are critically lacking. We have used in situ photoelectron spectroscopy and ex situ x-ray scattering to study D-A interfaces in tailored bilayers and BHJs based on small molecule donors. We show preferential miscibility at the D-A interface depending on molecular conformation in zinc phthalocyanine (ZnPc)/ C60 bilayers and we derive implications for exciton dissociation. Using sexithiophene (6T), a crystalline donor, we show that the energy landscape at the D-A interface varies markedly depending on the molecular composition of the BHJ. Both the ionization energies of sexithiophene and C60 shift by over ~0.4 eV while the energy of the charge transfer state shifts by ~0.5 eV depending on composition. Such shifts create a downward energy landscape that helps interfacial excitons to overcome their binding energies. Finally, we demonstrate that when both disordered and ordered phases of D coexist at the interface, low-lying energy states form in ordered phases and significantly limit the Voc in devices. Overall our work underlines the importance of the aggregation and conformation states of

  19. The conformational state of the nucleosome entry–exit site modulates TATA box-specific TBP binding

    Science.gov (United States)

    Hieb, Aaron R.; Gansen, Alexander; Böhm, Vera; Langowski, Jörg

    2014-01-01

    The TATA binding protein (TBP) is a critical transcription factor used for nucleating assembly of the RNA polymerase II machinery. TBP binds TATA box elements with high affinity and kinetic stability and in vivo is correlated with high levels of transcription activation. However, since most promoters use less stable TATA-less or TATA-like elements, while also competing with nucleosome occupancy, further mechanistic insight into TBP's DNA binding properties and ability to access chromatin is needed. Using bulk and single-molecule FRET, we find that TBP binds a minimal consensus TATA box as a two-state equilibrium process, showing no evidence for intermediate states. However, upon addition of flanking DNA sequence, we observe non-specific cooperative binding to multiple DNA sites that compete for TATA-box specificity. Thus, we conclude that TBP binding is defined by a branched pathway, wherein TBP initially binds with little sequence specificity and is thermodynamically positioned by its kinetic stability to the TATA box. Furthermore, we observed the real-time access of TBP binding to TATA box DNA located within the DNA entry–exit site of the nucleosome. From these data, we determined salt-dependent changes in the nucleosome conformation regulate TBP's access to the TATA box, where access is highly constrained under physiological conditions, but is alleviated by histone acetylation and TFIIA. PMID:24829456

  20. The conformational state of the nucleosome entry-exit site modulates TATA box-specific TBP binding.

    Science.gov (United States)

    Hieb, Aaron R; Gansen, Alexander; Böhm, Vera; Langowski, Jörg

    2014-07-01

    The TATA binding protein (TBP) is a critical transcription factor used for nucleating assembly of the RNA polymerase II machinery. TBP binds TATA box elements with high affinity and kinetic stability and in vivo is correlated with high levels of transcription activation. However, since most promoters use less stable TATA-less or TATA-like elements, while also competing with nucleosome occupancy, further mechanistic insight into TBP's DNA binding properties and ability to access chromatin is needed. Using bulk and single-molecule FRET, we find that TBP binds a minimal consensus TATA box as a two-state equilibrium process, showing no evidence for intermediate states. However, upon addition of flanking DNA sequence, we observe non-specific cooperative binding to multiple DNA sites that compete for TATA-box specificity. Thus, we conclude that TBP binding is defined by a branched pathway, wherein TBP initially binds with little sequence specificity and is thermodynamically positioned by its kinetic stability to the TATA box. Furthermore, we observed the real-time access of TBP binding to TATA box DNA located within the DNA entry-exit site of the nucleosome. From these data, we determined salt-dependent changes in the nucleosome conformation regulate TBP's access to the TATA box, where access is highly constrained under physiological conditions, but is alleviated by histone acetylation and TFIIA. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  1. 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.)

  2. 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

  3. Conformation and interactions of 4-(pyridinium-1-yl)-phenolate betaine-dye and its cation in the crystalline state

    Science.gov (United States)

    Wojtas, Łukasz; Pawlica, Dariusz; Stadnicka, Katarzyna

    2006-03-01

    The crystals of 4-(pyridinium-1-yl)-phenolate dihydrate, 1-(4-hydroxyphenyl)-pyridynium chloride monohydrate, 1-(4-hydroxyphenyl)-pyridynium phosphate dihydrate were obtained to explore the molecular behaviour of the simplest pyridynium betaine-dye in various crystalline environments. 4-(Pyridinium-1-yl)-phenolate ( 1), as a push-pull chromophore showing the negative solvatochromism of ICT band, can be useful in NLO applications if the polar dipole arrangement is achieved in the solid-state. The attempt to overcome the tendency of betaine dipoles to form anti-parallel arrangements was successful to some extent. X-ray structure analysis of the crystals, obtained from aqueous solutions, revealed space groups Pnna, P212121 and P2 1/ c, respectively. For 4-(pyridinium-1-yl)-phenolate dihydrate and 1-(4-hydroxyphenyl)-pyridynium chloride monohydrate, the anti-parallel arrangements of the betaine-dye molecules/cations force a nonpolar space group. In the centrosymmetrical crystals of 1-(4-hydroxyphenyl)-pyridynium phosphate dihydrate, between the centrosymmetric layers built of phosphate anions and water molecules, there are the polar arrangement of the betaine-dye cations connected to the phosphate-hydrate layers; however, the centrosymmetricity of the layers precludes the polarity of the structure. The alteration of geometrical parameters of the cation, as compared to 4-(pyridinium-1-yl)-phenolate molecule, is observed only in the phenolate moiety due to the protonation of the oxygen atom. A twisted conformation for the betaine-dye molecule observed in the crystalline state, with the dihedral angle of 47.0(1)°, is similar to the results of computational studies for the ground state of the single molecule in an aqueous solution. The influence of crystal environment, and that of the oxygen atom protonation, on the variation of the torsion angle is small.

  4. 40 CFR 93.154 - Conformity analysis.

    Science.gov (United States)

    2010-07-01

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

  5. From inactive to regular jogger

    DEFF Research Database (Denmark)

    Lund-Cramer, Pernille; Brinkmann Løite, Vibeke; Bredahl, Thomas Viskum Gjelstrup

    of Planned Behavior (TPB) and The Transtheoretical Model (TTM). Coding and analysis of interviews were performed using NVivo 10 software. Results TPB: During the behavior change process, the intention to jogging shifted from a focus on weight loss and improved fitness to both physical health, psychological......Title From inactive to regular jogger - a qualitative study of achieved behavioral change among recreational joggers Authors Pernille Lund-Cramer & Vibeke Brinkmann Løite Purpose Despite extensive knowledge of barriers to physical activity, most interventions promoting physical activity have proven...

  6. Social background, bullying, and physical inactivity

    DEFF Research Database (Denmark)

    Henriksen, P W; Rayce, S B; Melkevik, O

    2016-01-01

    More children from lower social backgrounds are physically inactive than those from higher ones. We studied whether bullying was a mediating factor between lower social background and physical inactivity. We also examined the combined effect of low social class and exposure to bullying on physical...... leaves 4.0% in the category physically inactive. The sex and age-adjusted OR (95% CI) for physical inactivity was 2.10 (1.39-3.18) among students with low social class and unclassifiable 3.53 (2.26-5.53). Exposure to bullying was associated with physical inactivity, sex and age-adjusted OR = 2.39 (1.......67-3.41). Exposure to bullying did not explain the association between social class and physical inactivity. The association between social class and physical inactivity was more pronounced among participants also exposed to bullying. In conclusion, there was a significantly increased odds ratio for physical...

  7. Workers’ Conformism

    Directory of Open Access Journals (Sweden)

    Nikolay Ivantchev

    2013-10-01

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

  8. From inactive to regular jogger

    DEFF Research Database (Denmark)

    Lund-Cramer, Pernille; Brinkmann Løite, Vibeke; Bredahl, Thomas Viskum Gjelstrup

    limited in terms of maintaining a behavior change. The purpose of this study was to investigate individual, cognitive, social, and contextual factors influencing the adoption and maintenance of regular self-organized jogging, and how they were manifested among former inactive adults. Methods A qualitative...... to translate intention into regular behavior. TTM: Informants expressed rapid progression from the pre-contemplation to the action stage caused by an early shift in the decisional balance towards advantages overweighing disadvantages. This was followed by a continuous improvement in self-efficacy, which...... jogging-related self-efficacy, and deployment of realistic goal setting was significant in the achievement of regular jogging behavior. Cognitive factors included a positive change in both affective and instrumental beliefs about jogging. Expectations from society and social relations had limited effect...

  9. 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.

  10. Conformal Infinity

    Directory of Open Access Journals (Sweden)

    Frauendiener Jörg

    2000-08-01

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

  11. 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.

  12. Conformity evaluation

    International Nuclear Information System (INIS)

    2010-01-01

    The conformity assessment activities involve the IRD's actions related to the CNEN regulatory processing for licensing and control of nuclear and radioactive facilities in the country. They include regulatory inspections of radiation protection

  13. Low postprandial circulating inactive ghrelin: role of early satiety in undernourished children.

    Science.gov (United States)

    Najib, Khadijehsadat; Moghtaderi, Mozhgan; Farjadian, Shirin; Falahzadeh, Ebrahim

    2014-11-01

    To determine difference in the levels of circulating inactive ghrelin between undernourished and healthy children. The present cross-sectional study was conducted in undernourished children from southwestern Iran, from July 2011 through July 2012. Postprandial inactive ghrelin levels were measured in 40 undernourished children and sex- and age-matched healthy controls by enzyme immunoassay. The levels of postprandial inactive ghrelin were considerably lower in undernourished compared to the healthy children (6.4 vs. 12.9, P < 0.001). Among the undernourished children, the level of inactive ghrelin was significantly lower in girls than in boys (5.8 vs. 7.1, P = 0.032). Thus, the levels of inactive ghrelin was found to be low in undernourished children compared to healthy children. Early loss of appetite might be a result of low circulating inactive ghrelin levels in the postprandial state in undernourished children.

  14. Vascular adaption to physical inactivity in humans

    OpenAIRE

    Bleeker, M.W.P.

    2006-01-01

    This thesis presents studies on vascular adaptation to physical inactivity and deconditioning. Although it is clear that physical inactivity is an important risk factor for cardiovascular disease, the underlying physiological mechanisms have not yet been elucidated. In contrast to physical inactivity, exercise decreases the risk for cardiovascular disease. This beneficial effect of exercise is partly due to changes in vascular function and structure. However, far less is known about vascular ...

  15. Accounting for conformational flexibility and torsional anharmonicity in the H + CH3CH2OH hydrogen abstraction reactions: a multi-path variational transition state theory study.

    Science.gov (United States)

    Meana-Pañeda, Rubén; Fernández-Ramos, Antonio

    2014-05-07

    This work reports a detailed theoretical study of the hydrogen abstraction reactions from ethanol by atomic hydrogen. The calculated thermal rate constants take into account torsional anharmonicity and conformational flexibility, in addition to the variational and tunneling effects. Specifically, the kinetics calculations were performed by using multi-path canonical variational transition state theory with least-action path tunneling corrections, to which we have added the two-dimensional non-separable method to take into account torsional anharmonicity. The multi-path thermal rate constant is expressed as a sum over conformational reaction channels. Each of these channels includes all the transition states that can be reached by internal rotations. The results show that, in the interval of temperatures between 250 and 2500 K, the account for multiple paths leads to higher thermal rate constants with respect to the single path approach, mainly at low and at high temperatures. In addition, torsional anharmonicity enhances the slope of the Arrhenius plot in this range of temperatures. Finally, we show that the incorporation of tunneling into the hydrogen abstraction reactions substantially changes the contribution of each of the transition states to the conformational reaction channel.

  16. Leisure Time Physical Inactivity and Sedentary Behaviour and Lifestyle Correlates among Students Aged 13–15 in the Association of Southeast Asian Nations (ASEAN Member States, 2007–2013

    Directory of Open Access Journals (Sweden)

    Karl Peltzer

    2016-02-01

    Full Text Available The aim of this study was to examine the relationship between self-reported leisure time physical inactivity frequency and sedentary behaviour and lifestyle correlates among school children in the Association of Southeast Asian Nations (ASEAN region. The analysis included 30,284 school children aged 13–15 years from seven ASEAN countries that participated in the Global School-based Student Health Survey (GSHS between 2007 and 2013. The measure asked about overall physical activity, walking or biking to school, and on time spent sitting. Overall, the prevalence of physical inactivity was 80.4%, ranging from 74.8% in Myanmar to 90.7% in Cambodia and sedentary behaviour 33.0%, ranging from 10.5% in Cambodia and Myanmar to 42.7% in Malaysia. In multivariate logistic regression, not walking or biking to school, not attending physical education classes, inadequate vegetable consumption and lack of protective factors (peer and parental or guardian support were associated with physical inactivity, and older age (14 and 15 years old, coming from an upper middle income country, being overweight or obese, attending physical education classes, alcohol use, loneliness, peer support and lack of parental or guardian supervision were associated with sedentary behaviour. In boys, lower socioeconomic status (in the form of having experienced hunger and coming from a low income or lower middle income country were additionally associated with physical inactivity, and in girls, higher socioeconomic status, not walking or biking to school and being bullied were additionally associated with sedentary behaviour. In conclusion, a very high prevalence of leisure physical inactivity and sedentary behaviour among school going adolescents in ASEAN was found and several factors identified that may inform physical activity promotion programmes in school-going adolescents in ASEAN.

  17. Leisure Time Physical Inactivity and Sedentary Behaviour and Lifestyle Correlates among Students Aged 13–15 in the Association of Southeast Asian Nations (ASEAN) Member States, 2007–2013

    Science.gov (United States)

    Peltzer, Karl; Pengpid, Supa

    2016-01-01

    The aim of this study was to examine the relationship between self-reported leisure time physical inactivity frequency and sedentary behaviour and lifestyle correlates among school children in the Association of Southeast Asian Nations (ASEAN) region. The analysis included 30,284 school children aged 13–15 years from seven ASEAN countries that participated in the Global School-based Student Health Survey (GSHS) between 2007 and 2013. The measure asked about overall physical activity, walking or biking to school, and on time spent sitting. Overall, the prevalence of physical inactivity was 80.4%, ranging from 74.8% in Myanmar to 90.7% in Cambodia and sedentary behaviour 33.0%, ranging from 10.5% in Cambodia and Myanmar to 42.7% in Malaysia. In multivariate logistic regression, not walking or biking to school, not attending physical education classes, inadequate vegetable consumption and lack of protective factors (peer and parental or guardian support) were associated with physical inactivity, and older age (14 and 15 years old), coming from an upper middle income country, being overweight or obese, attending physical education classes, alcohol use, loneliness, peer support and lack of parental or guardian supervision were associated with sedentary behaviour. In boys, lower socioeconomic status (in the form of having experienced hunger) and coming from a low income or lower middle income country were additionally associated with physical inactivity, and in girls, higher socioeconomic status, not walking or biking to school and being bullied were additionally associated with sedentary behaviour. In conclusion, a very high prevalence of leisure physical inactivity and sedentary behaviour among school going adolescents in ASEAN was found and several factors identified that may inform physical activity promotion programmes in school-going adolescents in ASEAN. PMID:26891312

  18. Leisure Time Physical Inactivity and Sedentary Behaviour and Lifestyle Correlates among Students Aged 13-15 in the Association of Southeast Asian Nations (ASEAN) Member States, 2007-2013.

    Science.gov (United States)

    Peltzer, Karl; Pengpid, Supa

    2016-02-15

    The aim of this study was to examine the relationship between self-reported leisure time physical inactivity frequency and sedentary behaviour and lifestyle correlates among school children in the Association of Southeast Asian Nations (ASEAN) region. The analysis included 30,284 school children aged 13-15 years from seven ASEAN countries that participated in the Global School-based Student Health Survey (GSHS) between 2007 and 2013. The measure asked about overall physical activity, walking or biking to school, and on time spent sitting. Overall, the prevalence of physical inactivity was 80.4%, ranging from 74.8% in Myanmar to 90.7% in Cambodia and sedentary behaviour 33.0%, ranging from 10.5% in Cambodia and Myanmar to 42.7% in Malaysia. In multivariate logistic regression, not walking or biking to school, not attending physical education classes, inadequate vegetable consumption and lack of protective factors (peer and parental or guardian support) were associated with physical inactivity, and older age (14 and 15 years old), coming from an upper middle income country, being overweight or obese, attending physical education classes, alcohol use, loneliness, peer support and lack of parental or guardian supervision were associated with sedentary behaviour. In boys, lower socioeconomic status (in the form of having experienced hunger) and coming from a low income or lower middle income country were additionally associated with physical inactivity, and in girls, higher socioeconomic status, not walking or biking to school and being bullied were additionally associated with sedentary behaviour. In conclusion, a very high prevalence of leisure physical inactivity and sedentary behaviour among school going adolescents in ASEAN was found and several factors identified that may inform physical activity promotion programmes in school-going adolescents in ASEAN.

  19. Structure of the HIV-1 Full-Length Capsid Protein in a Conformationally Trapped Unassembled State Induced by Small-Molecule Binding

    Energy Technology Data Exchange (ETDEWEB)

    Du, Shoucheng; Betts, Laurie; Yang, Ruifeng; Shi, Haibin; Concel, Jason; Ahn, Jinwoo; Aiken, Christopher; Zhang, Peijun; Yeh, Joanne I. (Pitt); (Vanderbilt); (UNC)

    2012-11-26

    The capsid (CA) protein plays crucial roles in HIV infection and replication, essential to viral maturation. The absence of high-resolution structural data on unassembled CA hinders the development of antivirals effective in inhibiting assembly. Unlike enzymes that have targetable, functional substrate-binding sites, the CA does not have a known site that affects catalytic or other innate activity, which can be more readily targeted in drug development efforts. We report the crystal structure of the HIV-1 CA, revealing the domain organization in the context of the wild-type full-length (FL) unassembled CA. The FL CA adopts an antiparallel dimer configuration, exhibiting a domain organization sterically incompatible with capsid assembly. A small compound, generated in situ during crystallization, is bound tightly at a hinge site ('H site'), indicating that binding at this interdomain region stabilizes the ADP conformation. Electron microscopy studies on nascent crystals reveal both dimeric and hexameric lattices coexisting within a single condition, in agreement with the interconvertibility of oligomeric forms and supporting the feasibility of promoting assembly-incompetent dimeric states. Solution characterization in the presence of the H-site ligand shows predominantly unassembled dimeric CA, even under conditions that promote assembly. Our structure elucidation of the HIV-1 FL CA and characterization of a potential allosteric binding site provides three-dimensional views of an assembly-defective conformation, a state targeted in, and thus directly relevant to, inhibitor development. Based on our findings, we propose an unprecedented means of preventing CA assembly, by 'conformationally trapping' CA in assembly-incompetent conformational states induced by H-site binding.

  20. Administrative Inactivity: Concept and Requirements of Legality

    Directory of Open Access Journals (Sweden)

    Sergey V. Yarkovoy

    2016-07-01

    Full Text Available The general concept of omission in law, as well as the concept and main features of inactivity on the part of executive bodies, other public administration agencies and their officials in their administrative law enforcement are examined, conditions of legality of such inactivity are under study

  1. Inactive nurses: a source for alleviating the nursing shortage?

    Science.gov (United States)

    Williams, Kimberly A; Stotts, R Craig; Jacob, Susan R; Stegbauer, Cheryl C; Roussel, Linda; Carter, Donna

    2006-04-01

    This study seeks to provide an understanding of why inactive registered nurses chose to become inactive and what they would require for them to return to nursing. In 2000, a shortage of 110,000 (6%) registered nurses existed in the United States. If the current trends continue, the shortage is projected to grow to 29% by 2020. One solution to the nursing shortage may be attracting nurses with inactive licenses back into employment. This study used a quantitative, cross-sectional survey design. Data analysis included descriptive and inferential statistics. Inactive nurses (N = 428) younger than 60 years in 1 Southern state were surveyed. A major portion (27.6%) of these nurses left nursing because of a conflict between parenting duties and scheduling requirements (13.5%) at work and indicated that they would return to nursing if given the opportunity to work part-time, especially if shifts were flexible and shorter. Although the group of registered nurses younger than 60 years do not constitute a large percentage of nurses in this country, they are a potential source of alleviating, to some extent, the critical nursing shortage. Employers can encourage many of these nurses to return to work by providing more flexible work schedules, including part-time and shorter shifts, as well as decreased workloads.

  2. Binding of the anticonvulsant drug lamotrigine and the neurotoxin batrachotoxin to voltage-gated sodium channels induces conformational changes associated with block and steady-state activation.

    Science.gov (United States)

    Cronin, Nora B; O'Reilly, Andrias; Duclohier, Hervé; Wallace, B A

    2003-03-21

    Voltage-gated sodium channels are dynamic membrane proteins characterized by rapid conformational changes that switch the molecule between closed resting, activated, and inactivated states. Sodium channels are specifically blocked by the anticonvulsant drug lamotrigine, which preferentially binds to the channel pore in the inactivated open state. Batrachotoxin is a lipid-soluble alkaloid that causes steady-state activation and binds in the inner pore of the sodium channel with overlapping but distinct molecular determinants from those of lamotrigine. Using circular dichroism spectroscopy on purified voltage-gated sodium channels from Electrophorus electricus, the secondary structures associated with the mixture of states present at equilibrium in the absence of these ligands were compared with specific stabilized states in their presence. As the channel shifts to open states, there appears to be a significant change in secondary structure to a more alpha-helical conformation. The observed changes are consistent with increased order involving the S6 segments that form the pore, the domain III-IV linker, and the P-loops that form the outer pore and selectivity filter. A molecular model has been constructed for the sodium channel based on its homology with the pore-forming regions of bacterial potassium channels, and automated docking of the crystal structure of lamotrigine with this model produces a structure in which the close contacts of the drug are with the residues previously identified by mutational studies as forming the binding site for this drug.

  3. Conformational changes in Akt1 activation probed by amide hydrogen/deuterium exchange and nano-electrospray ionization mass spectrometry†

    Science.gov (United States)

    Guo, Mingquan; Huang, Bill X.; Kim, Hee-Yong

    2009-01-01

    Amide hydrogen exchange coupled to nano-electrospray ionization mass spectrometry (nano-ESI-MS) has been used to identify and characterize localized conformational changes of Akt upon activation. Active or inactive Akt was incubated in D2O buffer, digested with pepsin, and analyzed by nano-ESI-MS to determine the deuterium incorporation. The hydrogen/deuterium (H/D) exchange profiles revealed that Akt undergoes considerable conformational changes in the core structures of all three individual domains after activation. In the PH domain, four β-strand (β1, β2 β5 and β6) regions containing membrane-binding residues displayed higher solvent accessibility in the inactive state, suggesting that the PH domain is readily available for the binding to the plasma membrane for activation. In contrast, these β-strands became less exposed or more folded in the active form, which is favored for the dissociation of Akt from the membrane. The beginning α-helix J region and the C-terminal locus (T450-470P) of the regulatory domain showed less folded structures that probably enable substrate entry. Our data also revealed detailed conformational changes of Akt in the kinase domain due to activation, some of which may be attributed to the interaction of the basic residues with phosphorylation sites. Our H/D exchange results indicating the conformational status of Akt at different activation states provided new insight for the regulation of this critical protein involved in cell survival. PMID:19462409

  4. Valence isomerization of quadricyclane-norbornadiene derivatives via triplet state. Correlation of the mechanism with triplet conformation of the olefinic moiety

    International Nuclear Information System (INIS)

    Nakabayashi, Kenichi; Nishino, Hideo; Toki, Susumu; Takamuku, Setsuo

    1989-01-01

    The mechanism of the valence isomerization between methyl 5-aryl-tetracyclo(3.2.0.0 2,7 0 4,6 )-heptane-1-carboxylate (1) and methyl 3-aryl-bicyclo[2.2.1]hepta-2,5-diene-2-carboxylate (2) under the triplet sensitization in benzene has been studied by pulse radiolysis and stationary experiments. The valence isomerization proceeds via a 1,3-biradical intermediate favorably to 1 for the phenyl derivatives where the most stable conformation of the corresponding olefinic analogue is a twisted form. In the case of 1-naphthyl derivatives where the conformation of the olefinic analogue is a planar form, an adiabatic cycloreversion of 1 to 2 takes place. An equilibrium state between a 1,3-biradical intermediate and a triplet state with a structure of norbornadiene is estimated for 2-naphthyl derivatives. Correlation of the mechanism for the valence isomerization with the conformation of corresponding olefinic analogue has been discussed on the basis of the potential energy surfaces for the isomerization. (author)

  5. Cross-linking with O-raffinose lowers oxygen affinity and stabilizes haemoglobin in a non-cooperative T-state conformation.

    Science.gov (United States)

    Jia, Yiping; Ramasamy, Somasundaram; Wood, Francine; Alayash, Abdu I; Rifkind, Joseph M

    2004-12-01

    O-R-polyHbA(0) is an intra- and intermolecularly O-raffinose cross-linked derivative of deoxygenated human haemoglobin developed as an oxygen therapeutic. When compared with its native protein (HbA(0)), O-R-polyHbA(0) was found to be locked in the T (tense) quaternary conformation with a lower oxygen affinity, a reduced Bohr effect (50% of HbA(0)) and no measurable cooperativity (h=1). The kinetics of oxygen and CO binding to the protein indicate lower 'on' rates and faster 'off' rates than HbA(0) and the absence of effects of inositol hexaphosphate (IHP) on the kinetics. Other properties consistent with a T-like conformation are inaccessibility of the betaCys-93 thiol group of O-R-polyHbA(0), the hyperfine splitting from nitrogen in the EPR spectrum of the Fe(II)NO complex of O-R-polyHbA(0) and decreased flexibility in the distal haem pocket, as indicated by low-spin bis-histidine complexes detected by EPR of oxidized chains. A comparison of the properties of O-R-polyHbA(0) with those of HbA(0) with and without IHP, as well as the reaction of nitrite with deoxygenated haemoglobin, provide additional insights into the variations in the conformation of T-state haemoglobin in solution (modifications of the T state produced by adding organic phosphates, like IHP and 2,3-diphosphoglycerate). Although the physiological ramifications of locking HbA(0) in the T conformation with the O-raffinose are still unknown, valuable insights into haemoglobin function are provided by these studies of O-R-polyHbA(0).

  6. Axiomatic conformal field theory

    International Nuclear Information System (INIS)

    Gaberdiel, M.R.; Goddard, P.

    2000-01-01

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

  7. Conformational Plasticity of the Cell-Penetrating Peptide SAP As Revealed by Solid-State19F-NMR and Circular Dichroism Spectroscopies.

    Science.gov (United States)

    Afonin, Sergii; Kubyshkin, Vladimir; Mykhailiuk, Pavel K; Komarov, Igor V; Ulrich, Anne S

    2017-07-13

    The cell-penetrating peptide SAP, which was designed as an amphipathic poly-l-proline helix II (PPII), was suggested to self-assemble into regular fibrils that are relevant for its internalization. Herein we have analyzed the structure of SAP in the membrane-bound state by solid-state 19 F-NMR, which revealed other structural states, in addition to the expected surface-aligned PPII. Trifluoromethyl-bicyclopentyl-glycine (CF 3 -Bpg) and two rigid isomers of trifluoromethyl-4,5-methanoprolines (CF 3 -MePro) were used as labels for 19 F-NMR analysis. The equilibria between different conformations of SAP were studied and were found to be shifted by the substituents at Pro-11. Synchrotron-CD results suggested that substituting Pro-11 by CF 3 -MePro governed the coil-to-PPII equilibrium in solution and in the presence of a lipid bilayer. Using CD and 19 F-NMR, we examined the slow kinetics of the association of SAP with membranes and the dependence of the SAP conformational dynamics on the lipid composition. The peptide did not bind to lipids in the solid ordered phase and aggregated only in the liquid ordered "raft"-like bilayers. Self-association could not be detected in solution or in the presence of liquid disordered membranes. Surface-bound amphipathic SAP in a nonaggregated state was structured as a mixture of nonideal extended conformations reflecting the equilibrium already present in solution, i.e., before binding to the membrane.

  8. Autonomic responses to exercise: deconditioning/inactivity.

    Science.gov (United States)

    Hughson, Richard L; Shoemaker, J Kevin

    2015-03-01

    Experimental models of physical inactivity associated with a sedentary lifestyle or extreme forms of inactivity with bed rest or spaceflight affect the balance between parasympathetic and sympathetic nervous system regulation of the cardiovascular system. Deconditioning effects are rapidly seen in the regulation of heart rate to compensate for physical modifications in blood volume and cardiac function. Reflex regulation of cardiovascular control during exercise by metaboreflex and baroreflex is altered by bed rest and spaceflight. These models of extreme inactivity provide a reference to guide physical activity requirements for optimal cardiovascular health. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Atomic details of near-transition state conformers for enzyme phosphoryl transfer revealed by MgF-3 rather than by phosphoranes.

    Science.gov (United States)

    Baxter, Nicola J; Bowler, Matthew W; Alizadeh, Tooba; Cliff, Matthew J; Hounslow, Andrea M; Wu, Bin; Berkowitz, David B; Williams, Nicholas H; Blackburn, G Michael; Waltho, Jonathan P

    2010-03-09

    Prior evidence supporting the direct observation of phosphorane intermediates in enzymatic phosphoryl transfer reactions was based on the interpretation of electron density corresponding to trigonal species bridging the donor and acceptor atoms. Close examination of the crystalline state of beta-phosphoglucomutase, the archetypal phosphorane intermediate-containing enzyme, reveals that the trigonal species is not PO-3 , but is MgF-3 (trifluoromagnesate). Although MgF-3 complexes are transition state analogues rather than phosphoryl group transfer reaction intermediates, the presence of fluorine nuclei in near-transition state conformations offers new opportunities to explore the nature of the interactions, in particular the independent measures of local electrostatic and hydrogen-bonding distributions using 19F NMR. Measurements on three beta-PGM-MgF-3 -sugar phosphate complexes show a remarkable relationship between NMR chemical shifts, primary isotope shifts, NOEs, cross hydrogen bond F...H-N scalar couplings, and the atomic positions determined from the high-resolution crystal structure of the beta-PGM-MgF--3 -G6P complex. The measurements provide independent validation of the structural and isoelectronic MgF--3 model of near-transition state conformations.

  10. Nucleotide-dependence of G-actin conformation from multiple molecular dynamics simulations and observation of a putatively polymerization-competent superclosed state.

    Science.gov (United States)

    Splettstoesser, Thomas; Noé, Frank; Oda, Toshiro; Smith, Jeremy C

    2009-08-01

    The assembly of monomeric G-actin into filamentous F-actin is nucleotide dependent: ATP-G-actin is favored for filament growth at the "barbed end" of F-actin, whereas ADP-G-actin tends to dissociate from the "pointed end." Structural differences between ATP- and ADP-G-actin are examined here using multiple molecular dynamics simulations. The "open" and "closed" conformational states of G-actin in aqueous solution are characterized, with either ATP or ADP in the nucleotide binding pocket. With both ATP and ADP bound, the open state closes in the absence of actin-bound profilin. The position of the nucleotide in the protein is found to be correlated with the degree of opening of the active site cleft. Further, the simulations reveal the existence of a structurally well-defined, compact, "superclosed" state of ATP-G-actin, as yet unseen crystallographically and absent in the ADP-G-actin simulations. The superclosed state resembles structurally the actin monomer in filament models derived from fiber diffraction and is putatively the polymerization competent conformation of ATP-G-actin. 2008 Wiley-Liss, Inc.

  11. Two conformational states of the membrane-associated Bacillus thuringiensis Cry4Ba δ-endotoxin complex revealed by electron crystallography: Implications for toxin-pore formation

    International Nuclear Information System (INIS)

    Ounjai, Puey; Unger, Vinzenz M.; Sigworth, Fred J.; Angsuthanasombat, Chanan

    2007-01-01

    The insecticidal nature of Cry δ-endotoxins produced by Bacillus thuringiensis is generally believed to be caused by their ability to form lytic pores in the midgut cell membrane of susceptible insect larvae. Here we have analyzed membrane-associated structures of the 65-kDa dipteran-active Cry4Ba toxin by electron crystallography. The membrane-associated toxin complex was crystallized in the presence of DMPC via detergent dialysis. Depending upon the charge of the adsorbed surface, 2D crystals of the oligomeric toxin complex have been captured in two distinct conformations. The projection maps of those crystals have been generated at 17 A resolution. Both complexes appeared to be trimeric; as in one crystal form, its projection structure revealed a symmetrical pinwheel-like shape with virtually no depression in the middle of the complex. The other form revealed a propeller-like conformation displaying an obvious hole in the center region, presumably representing the toxin-induced pore. These crystallographic data thus demonstrate for the first time that the 65-kDa activated Cry4Ba toxin in association with lipid membranes could exist in at least two different trimeric conformations, conceivably implying the closed and open states of the pore

  12. Dynamics differentiate between active and inactive inteins.

    Science.gov (United States)

    Cronin, Melissa; Coolbaugh, Michael J; Nellis, David; Zhu, Jianwei; Wood, David W; Nussinov, Ruth; Ma, Buyong

    2015-02-16

    The balance between stability and dynamics for active enzymes can be somewhat quantified by studies of intein splicing and cleaving reactions. Inteins catalyze the ligation of flanking host exteins while excising themselves. The potential for applications led to engineering of a mini-intein splicing domain, where the homing endonuclease domain of the Mycobacterium tuberculosis RecA (Mtu recA) intein was removed. The remaining domains were linked by several short peptides, but splicing activity in all was substantially lower than the full-length intein. Native splicing activity was restored in some cases by a V67L mutation. Using computations and experiments, we examine the impact of this mutation on the stability and conformational dynamics of the mini-intein splicing domain. Molecular dynamics simulations were used to delineate the factors that determine the active state, including the V67L mini-intein mutant, and peptide linker. We found that (1) the V67L mutation lowers the global fluctuations in all modeled mini-inteins, stabilizing the mini-intein constructs; (2) the connecting linker length affects intein dynamics; and (3) the flexibilities of the linker and intein core are higher in the active structure. We have observed that the interaction of the linker region and a turn region around residues 35-41 provides the pathway for the allostery interaction. Our experiments reveal that intein catalysis is characterized by non-linear Arrhenius plot, confirming the significant contribution of protein conformational dynamics to intein function. We conclude that while the V67L mutation stabilizes the global structure, cooperative dynamics of all intein regions appear more important for intein function than high stability. Our studies suggest that effectively quenching the conformational dynamics of an intein through engineered allosteric interactions could deactivate intein splicing or cleaving. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  13. Conformality lost

    International Nuclear Information System (INIS)

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

    2009-01-01

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

  14. Small-angle neutron scattering investigation of the chain conformation of lamellar polystyrene/isoprene phase in solid state

    International Nuclear Information System (INIS)

    Constantinescu, L.M.

    1994-01-01

    Small-angle neutron scattering has been used in the study of chain conformation of lamellar styrene/isoprene block copolymers oriented in large single crystals. The radius of gyration of deuterated polystyrene chains around the normal to the interface has been measured. By comparing this direct evolution of the lateral dimension of the chains with the average chain separation given by the molecular area (the surface available at the interface for each covalent bond linking the blocks together) we characterized the transverse interpenetration degree of the chains. The polystyrene chains are displayed in simple strata own micro-domains, without an important interpenetration. (Author) 9 Figs., 2 Tabs., 25 Refs

  15. Neural-network analysis of the vibrational spectra of N-acetyl L-alanyl N '-methyl amide conformational states

    DEFF Research Database (Denmark)

    Bohr, Henrik; Frimand, Kenneth; Jalkanen, Karl J.

    2001-01-01

    Density-functional theory (DFT) calculations utilizing the Becke 3LYP hybrid functional have been carried out for N-acetyl L-alanine N'-methylamide and examined with respect to the effect of water on the structure, the vibrational frequencies, vibrational absorption (VA), vibrational circular...... dichroism (VCD), Raman spectra, and Raman optical activity (ROA) intensities. The large changes due to hydration in the structures, and the relative stability of the conformer, reflected in the VA, VCD, Raman spectra, and ROA spectra observed experimentally, are reproduced by the DFT calculations. A neural...

  16. Reversible chair ↔ skew conformational interconversion of 1,3,2-dioxaphosphorinane ring in the solid state.

    Science.gov (United States)

    Řlepokura, Katarzyna Anna

    2016-02-01

    β-NH4[(MeO)2cDHAP] (where cDHAP is cyclic dihydroxyacetone phosphate) has been investigated by X-ray crystallography in the temperature range 350-100 K. Three reversible single-crystal-to-single-crystal phase transitions have been examined and four phases (high-, room-, medium- and low-temperature phase, HTP, RTP, MTP and LTP, respectively) have been structurally determined: HTP (at 350 K, P2(1)/a, Z = 24), RTP (290 K, P1, Z = 12), MTP (205 K, P2(1)/a, Z = 4) and LTP (100 K, P1, Z = 24). Various puckering modes of the 1,3,2-dioxaphosphorinane ring of the organic cyclic phosphate anion have been revealed in the crystal: chair and skew. The chair ↔ skew ring flipping, which has been shown to take place during the phase transitions, results in various populations of skew and chair conformers in different phases. The flexibility in the coordination geometry of ammonium cations is considered to assist in the conformational flexibility of the dioxaphosphorinane ring.

  17. 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.

  18. obesity a disease of inactivity?

    African Journals Online (AJOL)

    a nutritional disorder, and the result of a positive energy bal- ance and ... nutritional status, adipose tissue stores and state of training. This feedback control .... For each 'i, mind treadmill time, 1.5 k. Higherbaseline activity levels . . . of ,. Women who“quit~~"smo increased activity gain weight than those who quit smoking. 1'.

  19. Physical inactivity displays a mediator role in the association of diabetes and poverty: A spatiotemporal analysis

    Directory of Open Access Journals (Sweden)

    Lung-Chang Chien

    2017-11-01

    Full Text Available Physical inactivity is one of the risk factors of diabetes. In addition, physical inactivity is attributed to urbanization-related factors, such as poverty, which is also one of the risk factors of diabetes. We hypothesized that physical inactivity is a mediator in the association between diabetes and poverty, and that spatial heterogeneity exists in these relationships. This study adopted a spatiotemporal modelling approach to conduct this mediator analysis. From 2004-2011, data were collected at the county level in 48 contiguous states (with a total of 3,109 counties from the Behavioral Risk Factor Surveillance System (BRFSS and American Community Survey. Poverty percentage significantly affected physical inactivity prevalence and diabetes prevalence in two separate models. Using a model with both physical inactivity and poverty percentages as independent variables, we verified that physical inactivity prevalence is a significant mediator. In this model, physical inactivity prevalence resulted in a significant positive association with diabetes prevalence, and the influence of poverty percentage on diabetes prevalence was significantly reduced (P=0.0009. An advanced spatiotemporal analysis revealed that 32.65% of counties having a significant positive association between diabetes prevalence and physical inactivity prevalence also had a significant positive association between physical inactivity prevalence and poverty percentage. Those counties were also likely located in the South and Southeast of USA. In summary, the findings of this study demonstrate the mediating effect of physical inactivity between diabetes and poverty. When implementing diabetes prevention in communities with higher poverty, appropriate strategies to reduce the cost burden of physical activity programmes should be considered.

  20. Transferred nuclear Overhauser effect analyses of membrane-bound enkephalin analogues by sup 1 H nuclear magnetic resonance: Correlation between activities and membrane-bound conformations

    Energy Technology Data Exchange (ETDEWEB)

    Milon, Alain; Miyazawa, Tatsuo; Higashijima, Tsutomu (Univ. of Tokyo (Japan))

    1990-01-09

    Leu-enkephalin, (D-Ala{sup 2})Leu-enkephalin, and (D-Ala{sup 2})Leu-enkephalinamide (agonists) and (L-Ala{sup 2})Leu-enkephalin (inactive analogue) bind to lipid bilayer consisting of phosphatidylcholine and phosphatidylserine. The conformations that these compounds assume, once bound to perdeuterated phospholipid bilayer, have been shown to be unique, as shown by the transferred nuclear Overhauser effect (TRNOE) of {sup 1}H NMR spectroscopy. In addition, their location in the bilayer was analyzed by TRNOE in the presence of spin-labeled phospholipids. These analyses showed a clear relationship between the activity and the peptide-membrane interaction. The three active peptides, when bound to membranes, adopt the same conformation, characterized by a type II{prime} {beta}-turn around Gly{sup 3}-Phe and a {gamma}-turn around Gly{sup 2} (or D-Ala{sup 2}). The inactive analogue, (L-Ala{sup 2})Leu-enkephalin, displayed a completely different TRNOE pattern corresponding to a different conformation in the membrane-bound state. The tyrosine residue of the active compounds is not inserted into the interior of membrane, but it is inserted into the bilayer for the L-Ala{sup 2} analogue. According to these results, (L-Ala{sup 2})Leu-enkephalin may be explained to be inactive because the mode of binding to the membranes is different from that of active compounds.

  1. 40 CFR 52.2133 - General conformity.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 4 2010-07-01 2010-07-01 false General conformity. 52.2133 Section 52...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS (CONTINUED) South Carolina § 52.2133 General conformity. The General Conformity regulations adopted into the South Carolina State Implementation Plan which...

  2. 40 CFR 51.854 - Conformity analysis.

    Science.gov (United States)

    2010-07-01

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

  3. 40 CFR 52.938 - General conformity.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 3 2010-07-01 2010-07-01 false General conformity. 52.938 Section 52...) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Kentucky § 52.938 General conformity. The General Conformity regulations were submitted on November 10, 1995, and adopted into the Kentucky State...

  4. Identifying Conformational-Selection and Induced-Fit Aspects in the Binding-Induced Folding of PMI from Markov State Modeling of Atomistic Simulations.

    Science.gov (United States)

    Paul, Fabian; Noé, Frank; Weikl, Thomas R

    2018-03-27

    Unstructured proteins and peptides typically fold during binding to ligand proteins. A challenging problem is to identify the mechanism and kinetics of these binding-induced folding processes in experiments and atomistic simulations. In this Article, we present a detailed picture for the folding of the inhibitor peptide PMI into a helix during binding to the oncoprotein fragment 25-109 Mdm2 obtained from atomistic, explicit-water simulations and Markov state modeling. We find that binding-induced folding of PMI is highly parallel and can occur along a multitude of pathways. Some pathways are induced-fit-like with binding occurring prior to PMI helix formation, while other pathways are conformational-selection-like with binding after helix formation. On the majority of pathways, however, binding is intricately coupled to folding, without clear temporal ordering. A central feature of these pathways is PMI motion on the Mdm2 surface, along the binding groove of Mdm2 or over the rim of this groove. The native binding groove of Mdm2 thus appears as an asymmetric funnel for PMI binding. Overall, binding-induced folding of PMI does not fit into the classical picture of induced fit or conformational selection that implies a clear temporal ordering of binding and folding events. We argue that this holds in general for binding-induced folding processes because binding and folding events in these processes likely occur on similar time scales and do exhibit the time-scale separation required for temporal ordering.

  5. Low-resolution molecular models reveal the oligomeric state of the PPAR and the conformational organization of its domains in solution.

    Directory of Open Access Journals (Sweden)

    Amanda Bernardes

    Full Text Available The peroxisome proliferator-activated receptors (PPARs regulate genes involved in lipid and carbohydrate metabolism, and are targets of drugs approved for human use. Whereas the crystallographic structure of the complex of full length PPARγ and RXRα is known, structural alterations induced by heterodimer formation and DNA contacts are not well understood. Herein, we report a small-angle X-ray scattering analysis of the oligomeric state of hPPARγ alone and in the presence of retinoid X receptor (RXR. The results reveal that, in contrast with other studied nuclear receptors, which predominantly form dimers in solution, hPPARγ remains in the monomeric form by itself but forms heterodimers with hRXRα. The low-resolution models of hPPARγ/RXRα complexes predict significant changes in opening angle between heterodimerization partners (LBD and extended and asymmetric shape of the dimer (LBD-DBD as compared with X-ray structure of the full-length receptor bound to DNA. These differences between our SAXS models and the high-resolution crystallographic structure might suggest that there are different conformations of functional heterodimer complex in solution. Accordingly, hydrogen/deuterium exchange experiments reveal that the heterodimer binding to DNA promotes more compact and less solvent-accessible conformation of the receptor complex.

  6. The role of halogen C–X{sub 1}⋯X{sub 2}–C contact on the preferred conformation of 2-perhalomethylchromones in solid state

    Energy Technology Data Exchange (ETDEWEB)

    Alcívar León, C.D. [CEQUINOR (CONICET-UNLP), Facultad de Ciencias Exactas, Universidad Nacional de La Plata, 47 esq. 115, 1900 La Plata (Argentina); Echeverría, G.A.; Piro, O.E. [Departamento de Física, Facultad de Ciencias Exactas, Universidad Nacional de La Plata e IFLP (CONICET, CCT-La Plata), C. C. 67, 1900 La Plata (Argentina); Ulic, S.E., E-mail: sonia@quimica.unlp.edu.ar [CEQUINOR (CONICET-UNLP), Facultad de Ciencias Exactas, Universidad Nacional de La Plata, 47 esq. 115, 1900 La Plata (Argentina); Departamento de Ciencias Básicas, Universidad Nacional de Luján, Rutas 5 y 7, 6700 Luján, Buenos Aires (Argentina); Jios, J.L., E-mail: jljios@quimica.unlp.edu.ar [UNIDAD PLAPIMU-LASEISIC (UNLP-CIC), Departamento de Química, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, 47 esq. 115, 1900 La Plata (Argentina); Burgos Paci, M.; Argüello, G.A [INFIQC, Departamento de Físico Química, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba (Argentina)

    2016-06-15

    The solid state of 2-chlorodifluoromethyl-3-methylchromone (1) and 3-bromomethyl-2-chlorodifluoromethylchromone (2) was studied by vibrational spectroscopy (IR, Raman) and X-ray diffraction methods. The analysis was extended to solution phase using UV–Vis, NMR ({sup 1}H, {sup 13}C and {sup 19}F) and fluorescence spectroscopy with the assistance of theoretical calculations. The crystal structure of 2 shows chlorine and bromine atoms of the –CF{sub 2}Cl and –CH{sub 2}Br groups on the same side of the molecular plane, while in the most stable conformer predicted by theoretical calculations, these halogen atoms are opposite. These differences were interpreted in terms of intra- and intermolecular interactions in the crystal packing. Particularly, the weak non covalent halogen–halogen contact plays a decisive role in the preferred conformation adopted in solid phase. In addition, results of fluorescence spectroscopy are in accordance with the X-ray spectroscopy, since the proposed association due to intermolecular interactions was also found in solution when the concentration of 2 was increased.

  7. The role of halogen C–X1⋯X2–C contact on the preferred conformation of 2-perhalomethylchromones in solid state

    International Nuclear Information System (INIS)

    Alcívar León, C.D.; Echeverría, G.A.; Piro, O.E.; Ulic, S.E.; Jios, J.L.; Burgos Paci, M.; Argüello, G.A

    2016-01-01

    The solid state of 2-chlorodifluoromethyl-3-methylchromone (1) and 3-bromomethyl-2-chlorodifluoromethylchromone (2) was studied by vibrational spectroscopy (IR, Raman) and X-ray diffraction methods. The analysis was extended to solution phase using UV–Vis, NMR ( 1 H, 13 C and 19 F) and fluorescence spectroscopy with the assistance of theoretical calculations. The crystal structure of 2 shows chlorine and bromine atoms of the –CF 2 Cl and –CH 2 Br groups on the same side of the molecular plane, while in the most stable conformer predicted by theoretical calculations, these halogen atoms are opposite. These differences were interpreted in terms of intra- and intermolecular interactions in the crystal packing. Particularly, the weak non covalent halogen–halogen contact plays a decisive role in the preferred conformation adopted in solid phase. In addition, results of fluorescence spectroscopy are in accordance with the X-ray spectroscopy, since the proposed association due to intermolecular interactions was also found in solution when the concentration of 2 was increased.

  8. Prevalência de inatividade física e fatores associados em estudantes do ensino médio de escolas públicas estaduais Prevalence of physical inactivity and associated factors among high school students from state's public schools

    Directory of Open Access Journals (Sweden)

    Fabio L. Ceschini

    2009-08-01

    Full Text Available OBJETIVO: Descrever a prevalência de inatividade física e os fatores associados em estudantes do ensino médio de escolas públicas estaduais da cidade de São Paulo (SP. MÉTODOS: Foram selecionadas aleatoriamente 16 escolas públicas estaduais considerando as regiões geográficas da cidade de São Paulo (norte, sul, leste e oeste. A amostra foi de 3.845 estudantes do ensino médio no ano de 2006. Inatividade física foi mensurada com o Questionário Internacional de Atividade Física (IPAQ curto e definida como praticar atividade física moderada e/ou vigorosa por um período menor que 300 minutos por semana. As variáveis independentes analisadas foram: gênero, idade, nível socioeconômico, região geográfica da cidade de São Paulo, conhecimento do programa Agita São Paulo, participação nas aulas de educação física escolar, uso de tabaco, ingestão de bebidas alcoólicas e tempo diário assistindo televisão. Foi utilizada a regressão de Poisson com três níveis para entrada de variáveis, com nível de significância de p OBJECTIVE: To describe the prevalence of physical inactivity and associated factors among high school students from state's public schools in the city of São Paulo, state of São Paulo, Brazil. METHODS: Sixteen state's public schools were randomly selected according to the geographic areas of the city (North, South, East, and West. The sample consisted of 3,845 high school students in 2006. Physical inactivity was measured using the International Physical Activity Questionnaire (short IPAQ and was defined as practicing moderate and/or vigorous physical activity for a period of less than 300 minutes per week. The independent variables analyzed were: gender, age, socioeconomic level, geographic area of the city, awareness of the "Agita São Paulo" program, participation in physical education classes, smoking, alcohol intake and time spent per day watching television. Three-level Poisson regression was used for

  9. Short-term Physical Inactivity Impairs Vascular Function

    Science.gov (United States)

    Nosova, Emily V.; Yen, Priscilla; Chong, Karen C.; Alley, Hugh F.; Stock, Eveline O.; Quinn, Alex; Hellmann, Jason; Conte, Michael S.; Owens, Christopher D.; Spite, Matthew; Grenon, S. Marlene

    2014-01-01

    Introduction Sedentarism, also termed physical inactivity, is an independent risk factor for cardiovascular diseases. Mechanisms thought to be involved include insulin resistance, dyslipidemia, hypertension, and increased inflammation. It is unknown whether changes in vascular and endothelial function also contribute to this excess risk. We hypothesized that short-term exposure to inactivity would lead to endothelial dysfunction, arterial stiffening and increased vascular inflammation. Methods Five healthy subjects (4 males and 1 female) underwent 5 days of bed rest (BR) to simulate inactivity. Measurements of vascular function [flow-mediated vasodilation (FMD) to evaluate endothelial function; applanation tonometry to assess arterial resistance], inflammation and metabolism were made before BR, daily during BR and after 2 recovery days. Subjects maintained an isocaloric diet throughout. Results Bed rest led to significant decreases in brachial artery and femoral artery FMD [Brachial: 11 ± 3% pre-BR vs. 9 ± 2% end-BR, P=0.04; Femoral: 4 ± 1% vs. 2 ± 1%, P=0.04]. The central augmentation index increased with BR [−4 ± 9% vs. 5 ± 11%, P=0.03]. Diastolic blood pressure (DBP) increased [58 ± 7 mmHg vs. 62 ± 7 mmHg, P=0.02], while neither systolic blood pressure nor heart rate changed. 15-HETE, an arachidonic acid metabolite, increased but the other inflammatory and metabolic biomarkers were unchanged. Conclusions Our findings show that acute exposure to sedentarism results in decreased endothelial function, arterial stiffening, increased DBP, and an increase in 15-HETE. We speculate that inactivity promotes a vascular “deconditioning” state characterized by impaired endothelial function, leading to arterial stiffness and increased arterial tone. Although physiologically significant, the underlying mechanisms and clinical relevance of these findings need to be further explored. PMID:24630521

  10. 24 CFR 214.200 - Inactive status.

    Science.gov (United States)

    2010-04-01

    ... review. (b) Agencies that seek temporary inactive status must submit a request to HUD in writing... review and notify the agency of approval or rejection, in writing. If approved, the agency's name and contact information will be temporarily removed from the HUD-approved Web list of agencies and the...

  11. Effects of active, inactive and compounded Saccharomyces ...

    African Journals Online (AJOL)

    The objective of this research was to determine the effects of active, inactive and compounded Saccharomyces cerevisiae (SC) as natural feed additives on growth performance, visceral organs weight, insulin, thyroxin and growth hormone of Japanese quails. One day old Japanese quails allocated in 4 treatments by 4 ...

  12. Elective Mutism Associated with Selective Inactivity.

    Science.gov (United States)

    Hill, Linda; Scull, John

    1985-01-01

    Effective treatment procedures for a nine-year-old boy with elective mutism and selective inactivity included increasing the frequency of situations in which he could already speak and decreasing the frequency of those in which he seldom spoke (specifically coercive situations). (CL)

  13. The conformation of the Congo-red ligand bound to amyloid fibrils HET-s(218-289): a solid-state NMR study.

    Science.gov (United States)

    Gowda, Chandrakala; Zandomeneghi, Giorgia; Zimmermann, Herbert; Schütz, Anne K; Böckmann, Anja; Ernst, Matthias; Meier, Beat H

    2017-12-01

    We have previously shown that Congo red (CR) binds site specifically to amyloid fibrils formed by HET-s(218-289) with the long axis of the CR molecule almost parallel to the fibril axis. HADDOCK docking studies indicated that CR adopts a roughly planar conformation with the torsion angle ϕ characterizing the relative orientation of the two phenyl rings being a few degrees. In this study, we experimentally determine the torsion angle ϕ at the center of the CR molecule when bound to HET-s(218-289) amyloid fibrils using solid-state NMR tensor-correlation experiments. The method described here relies on the site-specific 13 C labeling of CR and on the analysis of the two-dimensional magic-angle spinning tensor-correlation spectrum of 13 C 2 -CR. We determined the torsion angle ϕ to be 19°.

  14. Effective Strategy for Conformer-Selective Detection of Short-Lived Excited State Species: Application to the IR Spectroscopy of the N1H Keto Tautomer of Guanine.

    Science.gov (United States)

    Asami, Hiroya; Tokugawa, Munefumi; Masaki, Yoshiaki; Ishiuchi, Shun-Ichi; Gloaguen, Eric; Seio, Kohji; Saigusa, Hiroyuki; Fujii, Masaaki; Sekine, Mitsuo; Mons, Michel

    2016-04-14

    The ultrafast deactivation processes in the excited state of biomolecules, such as the most stable tautomers of guanine, forbid any state-of-the-art gas phase spectroscopic studies on these species with nanosecond lasers. This drawback can be overcome by grafting a chromophore having a long-lived excited state to the molecule of interest, allowing thus a mass-selective detection by nanosecond R2PI and therefore double resonance IR/UV conformer-selective spectroscopic studies. The principle is presently demonstrated on the keto form of a modified 9-methylguanine, for which the IR/UV double resonance spectrum in the C═O stretch region, reported for the first time, provides evidence for extensive vibrational couplings within the guanine moiety. Such a successful strategy opens up a route to mass-selective IR/UV spectroscopic investigations on molecules exhibiting natural chromophores having ultrashort-lived excited states, such as DNA bases, their complexes as well as peptides containing short-lived aromatic residues.

  15. NiCo2O4@TiN Core-shell Electrodes through Conformal Atomic Layer Deposition for All-solid-state Supercapacitors

    International Nuclear Information System (INIS)

    Wang, Ruiqi; Xia, Chuan; Wei, Nini; Alshareef, Husam N.

    2016-01-01

    Highlights: • NiCo 2 O 4 nanostructures are prepared via a simple hydrothermal method. • Outer shell of TiN is then grown through conformal atomic layer deposition. • Electrodes exhibit significantly enhanced rate capability with TiN coating. • Solid-state polymer electrolyte is employed to improve cycling stability. • Full devices show a stack power density of 58.205 mW cm −3 at 0.061 mWh cm −3 . - Abstract: Ternary transition metal oxides such as NiCo 2 O 4 show great potential as supercapacitor electrode materials. However, the unsatisfactory rate performance of NiCo 2 O 4 may prove to be a major hurdle to its commercial usage. Herein, we report the development of NiCo 2 O 4 @TiN core–shell nanostructures for all-solid-state supercapacitors with significantly enhanced rate capability. We demonstrate that a thin layer of TiN conformally grown by atomic layer deposition (ALD) on NiCo 2 O 4 nanofiber arrays plays a key role in improving their electrical conductivity, mechanical stability, and rate performance. Fabricated using the hybrid NiCo 2 O 4 @TiN electrodes, the symmetric all-solid-state supercapacitor exhibited an impressive stack power density of 58.205 mW cm −3 at a stack energy density of 0.061 mWh cm −3 . To the best of our knowledge, these values are the highest of any NiCo 2 O 4 -based all-solid-state supercapacitor reported. Additionally, the resulting NiCo 2 O 4 @TiN all-solid-state device displayed outstanding cycling stability by retaining 70% of its original capacitance after 20,000 cycles at a high current density of 10 mA cm −2 . These results illustrate the promise of ALD-assisted hybrid NiCo 2 O 4 @TiN electrodes within sustainable and integrated energy storage applications.

  16. Increasing and decreasing motor and cognitive output: a model of general action and inaction goals.

    Science.gov (United States)

    Albarracín, Dolores; Handley, Ian M; Noguchi, Kenji; McCulloch, Kathleen C; Li, Hong; Leeper, Joshua; Brown, Rick D; Earl, Allison; Hart, William P

    2008-09-01

    General action and inaction goals can influence the amount of motor or cognitive output irrespective of the type of behavior in question, with the same stimuli producing trivial and important motor and cognitive manifestations normally viewed as parts of different systems. A series of experiments examined the effects of instilling general action and inaction goals using word primes, such as "action" and "rest." The first 5 experiments showed that the same stimuli influenced motor output, such as doodling on a piece of paper and eating, as well as cognitive output, such as recall and problem solving. The last 2 experiments supported the prediction that these diverse effects can result from the instigation of general action and inaction goals. Specifically, these last 2 studies confirmed that participants were motivated to achieve active or inactive states and that attaining them decreased the effects of the primes on behavior.

  17. Conformational instability of the lowest triplet state of the benzene nucleus: II. p-Xylene, the influence of substituents

    NARCIS (Netherlands)

    van der Waals, J.H.; van Hemert, M.C.; Buma, W.J.

    1990-01-01

    A calculation of the potential-energy surface of the lowest triplet state of p-xylene as a function of the S8(,) distortion coordinate of the benzene skeleton has been made to learn more about the influence of substituents on the vibronically induced distortion of benzene in its metastable triplet

  18. Conformation and chirality in liquid crystals

    Science.gov (United States)

    West, John L.; Zhao, Lei

    2013-09-01

    High helical twisting powerchiral additives are required for an expanding variety of liquid crystal displays and devices. Molecular conformation plays a critical role in determining the helical twisting power, HTP, of chiral additives. We studied additives based on an isosorbide benzoate ester core. Molecular modeling revealed two low energy states with very different conformations for this core The ultra-violet absorption and NMR spectra show two stable isosorbide conformers These spectra reveal how the relative populations of these two conformations change with temperature and how this is related to the helical twisting power. Conformation changes can explain many of the observed anomalous responses of HPT to temperature.

  19. Conformations and Conformational Processes of Hexahydrobenzazocines by NMR and DFT Studies.

    Science.gov (United States)

    Musielak, Bogdan; Holak, Tad A; Rys, Barbara

    2015-09-18

    Conformational processes that occur in hexahydrobenzazocines have been studied with the (1)H and (13)C dynamic nuclear magnetic resonance (DNMR) spectroscopy. The coalescence effects are assigned to two different conformational processes: the ring-inversion of the ground-state conformations and the interconversion between two different conformers. The barriers for these processes are in the range of 42-52 and 42-43 kJ mol(-1), respectively. Molecular modeling on the density functional theory (DFT) level and the gauge invariant atomic orbitals (GIAO)-DFT calculations of isotropic shieldings and coupling constants for the set of low-energy conformations were compared with the experimental NMR data. The ground-state of all compounds in solution is the boat-chair (BC) conformation. The BC form adopts two different conformations because the nitrogen atom can be in the boat or chair parts of the BC structure. These two conformers are engaged in the interconversion process.

  20. Physical Inactivity, Sedentary Behavior and Chronic Diseases

    OpenAIRE

    Gonz?lez, Karim?; Fuentes, Jorge; M?rquez, Jos? Luis

    2017-01-01

    New research into physical activity suggests that it is no longer sufficient just to meet minimum levels recommended by health guidelines in order to reduce cardiovascular risk. Both physical inactivity and sedentary behavior have their own health hazards and need to be addressed separately, in order to explore their different deleterious mechanisms. The aim of this review was to define and to characterize both concepts, and their relationship with major non-communicable chronic diseases. A P...

  1. Molecular Dynamics Simulation and Experimental Studies on the Visual Pigment Rhodopsin: Multiple Conformational States and Structural Changes

    CERN Document Server

    Kholmurodov, Kh T; Ostrovsky, M A; Biochemical Physics Institute, Russian Academy of Sciences, Moscow, Russia

    2005-01-01

    Based on the MD simulations with a supercomputer and the special-purposes MDGRAPE-2 machine we have performed 3-ns MD calculations on the rhodopsin molecule and presented the structure analysis data for its dark-adapted state. We have fulfilled the RMSD (root-mean-square deviation) and structural analysis for the rhodopsin (with 11-\\textit{cis} retinal), generated the pictures of the atomic-scale processes for the binding pocket, surrounding the chromophore retinal, and compared the helical deviations for the beta-ionone ring and Schiff base linkage regions of the protein. The most remarkable point of our observations is that the rhodopsin helical distortions in the dark state are accompanied with the transformation of the retinal chromophore, viz. with the rotation of the beta-ionone ring inside the protein binding pocket. The low-temperature absorption spectroscopy technique has been used to study the primary stages of rhodopsin photolysis. The structural transformation properties of rhodopsin were discusse...

  2. Exploring human inactivity in computer power consumption

    Science.gov (United States)

    Candrawati, Ria; Hashim, Nor Laily Binti

    2016-08-01

    Managing computer power consumption has become an important challenge in computer society and this is consistent with a trend where a computer system is more important to modern life together with a request for increased computing power and functions continuously. Unfortunately, previous approaches are still inadequately designed to handle the power consumption problem due to unpredictable workload of a system caused by unpredictable human behaviors. This is happens due to lack of knowledge in a software system and the software self-adaptation is one approach in dealing with this source of uncertainty. Human inactivity is handled by adapting the behavioral changes of the users. This paper observes human inactivity in the computer usage and finds that computer power usage can be reduced if the idle period can be intelligently sensed from the user activities. This study introduces Control, Learn and Knowledge model that adapts the Monitor, Analyze, Planning, Execute control loop integrates with Q Learning algorithm to learn human inactivity period to minimize the computer power consumption. An experiment to evaluate this model was conducted using three case studies with same activities. The result show that the proposed model obtained those 5 out of 12 activities shows the power decreasing compared to others.

  3. NiCo2O4@TiN Core-shell Electrodes through Conformal Atomic Layer Deposition for All-solid-state Supercapacitors

    KAUST Repository

    Wang, Renqi

    2016-03-04

    Ternary transition metal oxides such as NiCo2O4 show great promise as supercapacitor electrode materials. However, the unsatisfactory rate performance of NiCo2O4 may prove to be a major hurdle to its commercial usage. Herein, we report the development of NiCo2O4@TiN core–shell nanostructures for all-solid-state supercapacitors with significantly enhanced rate capability. We demonstrate that a thin layer of TiN conformally grown by atomic layer deposition (ALD) on NiCo2O4 nanofiber arrays plays a key role in improving their electrical conductivity, mechanical stability, and rate performance. Fabricated using the hybrid NiCo2O4@TiN electrodes, the symmetric all-solid-state supercapacitor exhibited an impressive stack power density of 58.205 mW cm−3 at a stack energy density of 0.061 mWh cm−3. To the best of our knowledge, these values are the highest of any NiCo2O4-based all-solid-state supercapacitor reported. Additionally, the resulting NiCo2O4@TiN all-solid-state device displayed outstanding cycling stability by retaining 70% of its original capacitance after 20,000 cycles at a high current density of 10 mA cm−2. These results illustrate the promise of ALD-assisted hybrid NiCo2O4@TiN electrodes for sustainable and integrated energy storage applications.

  4. [Physical inactivity and associated factors in adults, São Paulo, Brazil].

    Science.gov (United States)

    Zanchetta, Luane Margarete; Barros, Marilisa Berti de Azevedo; César, Chester Luiz Galvão; Carandina, Luana; Goldbaum, Moisés; Alves, Maria Cecília Goi Porto

    2010-09-01

    To analyze the prevalence of overall and leisure time physical inactivity and associated factors and types of exercises or sports modalities according to schooling in 2,050 adults from 18 to 59 years of age - state of São Paulo, Brazil. Population-based cross-sectional study with a stratified sample of clusters performed in multiple stages. Physical inactivity was determined using the short version of the International Physical Activity Questionnaire - IPAQ and by a question on the regular practice of leisure time physical activity. Data analysis took the sample design into account. Prevalence of physical inactivity during leisure was higher among women. Poisson multiple regression model in man indicated that overall sedentarism was lower among single and separated men, students and without car in the household. Leisure physical inactivity was greater among men over forty years, among those with less schooling and full-time students. Overall physical inactivity was more prevalent among woman with more schooling, with less qualified occupations and widows. Leisure physical inactivity decreased with age and schooling. Among modalities practiced for leisure, walking was more prevalent among women and football was more prevalent among men. Most modalities were directly associated with schooling; approximately 25% of the individuals with more than 12 years of schooling practiced walking. These results suggest that interventions and public policies to promote physical activity should consider differences in gender and socioeconomic status as well as the preferences for different modalities and the context in which the physical activity is practiced.

  5. Conformational Changes in the Hepatitis B Virus Core Protein Are Consistent with a Role for Allostery in Virus Assembly

    Energy Technology Data Exchange (ETDEWEB)

    Packianathan, Charles; Katen, Sarah P.; Dann, III, Charles E.; Zlotnick, Adam (Indiana)

    2010-01-12

    In infected cells, virus components must be organized at the right place and time to ensure assembly of infectious virions. From a different perspective, assembly must be prevented until all components are available. Hypothetically, this can be achieved by allosterically controlling assembly. Consistent with this hypothesis, here we show that the structure of the hepatitis B virus (HBV) core protein dimer, which can spontaneously self-assemble, is incompatible with capsid assembly. Systematic differences between core protein dimer and capsid conformations demonstrate linkage between the intradimer interface and interdimer contact surface. These structures also provide explanations for the capsid-dimer selectivity of some antibodies and the activities of assembly effectors. Solution studies suggest that the assembly-inactive state is more accurately an ensemble of conformations. Simulations show that allostery supports controlled assembly and results in capsids that are resistant to dissociation. We propose that allostery, as demonstrated in HBV, is common to most self-assembling viruses.

  6. The Global Physical Inactivity Pandemic: An Analysis of Knowledge Production

    Science.gov (United States)

    Piggin, Joe; Bairner, Alan

    2016-01-01

    In July 2012, "The Lancet" announced a pandemic of physical inactivity and a global call to action to effect change. The worldwide pandemic is said to be claiming millions of lives every year. Asserting that physical inactivity is pandemic is an important moment. Given the purported scale and significance of physical inactivity around…

  7. Impact of inactivity and exercise on the vasculature in humans.

    NARCIS (Netherlands)

    Thijssen, D.H.J.; Maiorana, A.J.; O'Driscoll, G.; Cable, N.T.; Hopman, M.T.E.; Green, D.J.

    2010-01-01

    The effects of inactivity and exercise training on established and novel cardiovascular risk factors are relatively modest and do not account for the impact of inactivity and exercise on vascular risk. We examine evidence that inactivity and exercise have direct effects on both vasculature function

  8. Crystal structures of the FAK kinase in complex with TAE226 and related bis-anilino pyrimidine inhibitors reveal a helical DFG conformation.

    Directory of Open Access Journals (Sweden)

    Daniel Lietha

    Full Text Available Focal Adhesion Kinase (FAK is a non-receptor tyrosine kinase required for cell migration, proliferation and survival. FAK overexpression has been documented in diverse human cancers and is associated with a poor clinical outcome. Recently, a novel bis-anilino pyrimidine inhibitor, TAE226, was reported to efficiently inhibit FAK signaling, arrest tumor growth and invasion and prolong the life of mice with glioma or ovarian tumor implants. Here we describe the crystal structures of the FAK kinase bound to TAE226 and three related bis-anilino pyrimidine compounds. TAE226 induces a conformation of the N-terminal portion of the kinase activation loop that is only observed in FAK, but is distinct from the conformation in both the active and inactive states of the kinase. This conformation appears to require a glycine immediately N-terminal to the "DFG motif", which adopts a helical conformation stabilized by interactions with TAE226. The presence of a glycine residue in this position contributes to the specificity of TAE226 and related compounds for FAK. Our work highlights the fact that kinases can access conformational space that is not necessarily utilized for their native catalytic regulation, and that such conformations can explain and be exploited for inhibitor specificity.

  9. 45 CFR 1355.34 - Criteria for determining substantial conformity.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Criteria for determining substantial conformity... GENERAL § 1355.34 Criteria for determining substantial conformity. (a) Criteria to be satisfied. ACF will determine a State's substantial conformity with title IV-B and title IV-E State plan requirements based on...

  10. Conformal Einstein spaces

    International Nuclear Information System (INIS)

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

    1985-01-01

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

  11. 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....

  12. Operator algebras and conformal field theory

    International Nuclear Information System (INIS)

    Gabbiani, F.; Froehlich, J.

    1993-01-01

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

  13. Superspace conformal field theory

    International Nuclear Information System (INIS)

    Quella, Thomas

    2013-07-01

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

  14. 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.

  15. Potential clinical translation of juvenile rodent inactivity models to study the onset of childhood obesity

    OpenAIRE

    Roberts, Michael D.; Company, Joseph M.; Brown, Jacob D.; Toedebusch, Ryan G.; Padilla, Jaume; Jenkins, Nathan T.; Laughlin, M. Harold; Booth, Frank W.

    2012-01-01

    According to the latest data from the Center for Disease Control and Prevention 17%, or 12.5 million, of children and adolescents aged 2–19 years in the United States are obese. Physical inactivity is designated as one of the actual causes of US deaths and undoubtedly contributes to the obesity epidemic in children and adults. Examining the effects of inactivity on physiological homeostasis during youth is crucial given that 58% of children between the ages 6–11 yr old fail to obtain the reco...

  16. 37 CFR 11.19 - Disciplinary jurisdiction; Jurisdiction to transfer to disability inactive status.

    Science.gov (United States)

    2010-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Disciplinary jurisdiction; Jurisdiction to transfer to disability inactive status. 11.19 Section 11.19 Patents, Trademarks, and Copyrights... UNITED STATES PATENT AND TRADEMARK OFFICE Investigations and Disciplinary Proceedings; Jurisdiction...

  17. The inactive X chromosome in the human female is enriched in 5 ...

    Indian Academy of Sciences (India)

    Unknown

    J. Genet. 82, 13–16]. Introduction. The hypothesis that methylation of cytosine residues in. DNA is a key step in the maintenance of the inactive state of the mammalian X chromosome (Holliday and. Pugh 1975; Riggs 1975) has found support from several types of experiment (Liskay and Evans 1980; Mohandas et al. 1981).

  18. 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

    2011-12-07

    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. Copyright © 2011 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  19. 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

  20. Unemployment, Employment and Inactivity in Denmark: An Analysis of Event History Data

    DEFF Research Database (Denmark)

    Lauzadyté, Agné

    In this paper I estimate a discrete time hazard model for the exits from the different labour market states - unemployment, employment and inactivity (or OLF) - in the Danish labour market. I find that women and individuals over fifty are more likely to experience the long-term unemployment...... and inactivity. The less educated and unskilled workers are found to be another risk group to face the marginalisation from the labour market. Being previously employed reduces the risk of OLF, and increases the re-entry to employment probability, while living in the biggest Danish cities makes persons...... disadvantaged. These give the evidence that the "Flexicurity"model makes the weakest individuals disadvantaged in the Danish labour market. And finally, I find that those, who survived in a job one year, tend to remain employed, while persons, longer than one year inactive, face much higher risk...

  1. 77 FR 59100 - Approval and Promulgation of Implementation Plans; Alabama: General and Transportation Conformity...

    Science.gov (United States)

    2012-09-26

    ... Promulgation of Implementation Plans; Alabama: General and Transportation Conformity & New Source Review... (SMC) Rule. The SIP revision also changes the State's general and transportation conformity regulations... federal general and transportation conformity regulations into the SIP. Alabama's May 2, 2011, SIP...

  2. 78 FR 68005 - Approval and Promulgation of Implementation Plans; Mississippi; Transportation Conformity SIP...

    Science.gov (United States)

    2013-11-13

    ...] Approval and Promulgation of Implementation Plans; Mississippi; Transportation Conformity SIP--Memorandum... transportation conformity criteria and procedures related to interagency consultation and enforceability of... conformity process to allow direct consultation among agencies at the Federal, state and local levels. This...

  3. Development of closure criteria for inactive radioactive waste disposal sites at Oak Ridge National Laboratory

    International Nuclear Information System (INIS)

    Kocher, D.C.

    1989-01-01

    The Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA), as amended, specifies that cleanup of inactive waste disposal sites at Department of Energy (DOE) facilities shall at least attain legally applicable or relevant and appropriate requirements (ARARs) for cleanup or control of environmental contamination. This paper discusses potential ARARs for cleanup of inactive radioactive waste disposal sites and proposes a set of closure criteria for such sites at Oak Ridge National Laboratory (ORNL). The most important potential ARARs include Federal standards for radiation protection of the public, radioactivity in drinking water, and near-surface land disposal of radioactive wastes. On the basis of these standards, we propose that cleanup and closure of inactive radioactive waste disposal sites at ORNL shall achieve (1) limits on annual effective dose equivalent for off-site individuals and inadvertent intruders that conform to the DOE's performance objectives for new low-level waste disposal facilities and (2) to the extent reasonably achievable, limits on radionuclide concentrations in ground water and surface waters in accordance with Federal drinking water standards and ground-water protection requirements

  4. Transmembrane potential polarization, calcium influx, and receptor conformational state modulate the sensitivity of the imidacloprid-insensitive neuronal insect nicotinic acetylcholine receptor to neonicotinoid insecticides.

    Science.gov (United States)

    Bodereau-Dubois, Béatrice; List, Olivier; Calas-List, Delphine; Marques, Olivier; Communal, Pierre-Yves; Thany, Steeve H; Lapied, Bruno

    2012-05-01

    Neonicotinoid insecticides act selectively on insect nicotinic acetylcholine receptors (nAChRs). Recent studies revealed that their efficiency was altered by the phosphorylation/dephosphorylation process and the intracellular signaling pathway involved in the regulation of nAChRs. Using whole-cell patch-clamp electrophysiology adapted for dissociated cockroach dorsal unpaired median (DUM) neurons, we demonstrated that intracellular factors involved in the regulation of nAChR function modulated neonicotinoid sensitivity. DUM neurons were known to express two α-bungarotoxin-insensitive nAChR subtypes: nAChR1 and nAChR2. Whereas nAChR1 was sensitive to imidacloprid, nAChR2 was insensitive to this insecticide. Here, we demonstrated that, like nicotine, acetamiprid and clothianidin, other types of neonicotinoid insecticides, acted as agonists on the nAChR2 subtype. Using acetamiprid, we revealed that both steady-state depolarization and hyperpolarization affected nAChR2 sensitivity. The measurement of the input membrane resistance indicated that change in the acetamiprid-induced agonist activity was related to the receptor conformational state. Using cadmium chloride, ω-conotoxin GVIA, and (R,S)-(3,4-dihydro-6,7-dimethoxy-isoquinoline-1-yl)-2-phenyl-N,N-di-acetamide (LOE 908), we found that inhibition of calcium influx through high voltage-activated calcium channels and transient receptor potential γ (TRPγ) activated by both depolarization and hyperpolarization increased nAChR2 sensitivity to acetamiprid. Finally, using N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride (W7), forskolin, and cAMP, we demonstrated that adenylyl cyclase sensitive to the calcium/calmodulin complex regulated internal cAMP concentration, which in turn modulated TRPγ function and nAChR2 sensitivity to acetamiprid. Similar TRPγ-induced modulatory effects were also obtained when clothianidin was tested. These findings bring insights into the signaling pathway modulating

  5. Changes in diagnosed diabetes, obesity, and physical inactivity prevalence in US counties, 2004-2012.

    Directory of Open Access Journals (Sweden)

    Linda S Geiss

    Full Text Available Recent studies suggest that prevalence of diagnosed diabetes in the United States reached a plateau or slowed around 2008, and that this change coincided with obesity plateaus and increases in physical activity. However, national estimates can obscure important variations in geographic subgroups. We examine whether a slowing or leveling off in diagnosed diabetes, obesity, and leisure time physical inactivity prevalence is also evident across the 3143 counties of the United States. We used publicly available county estimates of the age-adjusted prevalence of diagnosed diabetes, obesity, and leisure-time physical inactivity, which were generated by the Centers for Disease Control and Prevention (CDC. Using a Bayesian multilevel regression that included random effects by county and year and applied cubic splines to smooth these estimates over time, we estimated the average annual percentage point change (APPC from 2004 to 2008 and from 2008 to 2012 for diabetes, obesity, and physical inactivity prevalence in each county. Compared to 2004-2008, the median APPCs for diabetes, obesity, and physical inactivity were lower in 2008-2012 (diabetes APPC difference = 0.16, 95%CI 0.14, 0.18; obesity APPC difference = 0.65, 95%CI 0.59, 0.70; physical inactivity APPC difference = 0.43, 95%CI 0.37, 0.48. APPCs and APPC differences between time periods varied among counties and U.S. regions. Despite improvements, levels of these risk factors remained high with most counties merely slowing rather than reversing, which suggests that all counties would likely benefit from reductions in these risk factors. The diversity of trajectories in the prevalence of these risk factors across counties underscores the continued need to identify high risk areas and populations for preventive interventions. Awareness of how these factors are changing might assist local policy makers in targeting and tracking the impact of efforts to reduce diabetes, obesity and physical inactivity.

  6. Solid-state conformation of copolymers of ß-benzyl-L-aspartate with L-alanine, L-leucine, L-valine, γ-benzyl-L-glutamate, or ε-carbobenzoxy-L-lysine

    NARCIS (Netherlands)

    Sederel, Willem L.; Bantjes, Adriaan; Feijen, Jan; Anderson, James M.

    1980-01-01

    The solid-state conformation of copolymers of ß-benzyl-L-aspartate [L-Asp(OBzl)] with L-leucine (L-Leu), L-alanine (L-Ala), L-valine (L-Val), γ-benzyl-L-glutamate [L-Glu(OBzl)], or ε-carbobenzoxy-L-lysine (Cbz-L-Lys) has been studied by ir spectroscopy and circular dichroism (CD). The ir spectra in

  7. The economic cost of physical inactivity in China.

    Science.gov (United States)

    Zhang, Juan; Chaaban, Jad

    2013-01-01

    To estimate the total economic burden of physical inactivity in China. The costs of physical inactivity combine the medical and non-medical costs of five major Non Communicable Diseases (NCDs) associated with inactivity. The national data from the Chinese Behavioral Risk Factors Surveillance Surveys (2007) and the National Health Service Survey (2003) are used to compute population attributable risks (PARs) of inactivity for each major NCD. Costs specific to inactivity are obtained by multiplying each disease costs by the PAR for each NCD, by incorporating the inactivity effects through overweight and obesity. Physical inactivity contributes between 12% and 19% to the risks associated with the five major NCDs in China, namely coronary heart disease, stroke, hypertension, cancer, and type 2 diabetes. Physical inactivity is imposing a substantial economic burden on the country, as it is responsible alone for more than 15% of the medical and non-medical yearly costs of the main NCDs in the country. The high economic burden of physical inactivity implies the need to develop more programs and interventions that address this modifiable behavioral risk, in order to curb the rising NCDs epidemic in China. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. The Role of Conserved Waters in Conformational Transitions of Q61H K-ras

    Science.gov (United States)

    Prakash, Priyanka; Sayyed-Ahmad, Abdallah; Gorfe, Alemayehu A.

    2012-01-01

    To investigate the stability and functional role of long-residence water molecules in the Q61H variant of the signaling protein K-ras, we analyzed all available Ras crystal structures and conformers derived from a series of independent explicit solvent molecular dynamics (MD) simulations totaling 1.76 µs. We show that the protein samples a different region of phase space in the presence and absence of several crystallographically conserved and buried water molecules. The dynamics of these waters is coupled with the local as well as the global motions of the protein, in contrast to less buried waters whose exchange with bulk is only loosely coupled with the motion of loops in their vicinity. Aided by two novel reaction coordinates involving the distance (d) between the Cα atoms of G60 at switch 2 and G10 at the P-loop and the N-Cα-C-O dihedral (ξ) of G60, we further show that three water molecules located in lobe1, at the interface between the lobes and at lobe2, are involved in the relative motion of residues at the two lobes of Q61H K-ras. Moreover, a d/ξ plot classifies the available Ras x-ray structures and MD-derived K-ras conformers into active GTP-, intermediate GTP-, inactive GDP-bound, and nucleotide-free conformational states. The population of these states and the transition between them is modulated by water-mediated correlated motions involving the functionally critical switch 2, P-loop and helix 3. These results suggest that water molecules act as allosteric ligands to induce a population shift among distinct switch 2 conformations that differ in effector recognition. PMID:22359497

  9. Inhibition of Inactive States of Tetrodotoxin-Sensitive Sodium Channels Reduces Spontaneous Firing of C-Fiber Nociceptors and Produces Analgesia in Formalin and Complete Freund's Adjuvant Models of Pain.

    Directory of Open Access Journals (Sweden)

    David J Matson

    Full Text Available While genetic evidence shows that the Nav1.7 voltage-gated sodium ion channel is a key regulator of pain, it is unclear exactly how Nav1.7 governs neuronal firing and what biophysical, physiological, and distribution properties of a pharmacological Nav1.7 inhibitor are required to produce analgesia. Here we characterize a series of aminotriazine inhibitors of Nav1.7 in vitro and in rodent models of pain and test the effects of the previously reported "compound 52" aminotriazine inhibitor on the spiking properties of nociceptors in vivo. Multiple aminotriazines, including some with low terminal brain to plasma concentration ratios, showed analgesic efficacy in the formalin model of pain. Effective concentrations were consistent with the in vitro potency as measured on partially-inactivated Nav1.7 but were far below concentrations required to inhibit non-inactivated Nav1.7. Compound 52 also reversed thermal hyperalgesia in the complete Freund's adjuvant (CFA model of pain. To study neuronal mechanisms, electrophysiological recordings were made in vivo from single nociceptive fibers from the rat tibial nerve one day after CFA injection. Compound 52 reduced the spontaneous firing of C-fiber nociceptors from approximately 0.7 Hz to 0.2 Hz and decreased the number of action potentials evoked by suprathreshold tactile and heat stimuli. It did not, however, appreciably alter the C-fiber thresholds for response to tactile or thermal stimuli. Surprisingly, compound 52 did not affect spontaneous activity or evoked responses of Aδ-fiber nociceptors. Results suggest that inhibition of inactivated states of TTX-S channels, mostly likely Nav1.7, in the peripheral nervous system produces analgesia by regulating the spontaneous discharge of C-fiber nociceptors.

  10. Genetic parameters between feed-intake-related traits and conformation in 2 separate dairy populations-the Netherlands and United States

    NARCIS (Netherlands)

    Manzanilla-Pech, C.I.V.; Veerkamp, R.F.; Tempelman, R.J.; Pelt, van M.L.; Weigel, K.A.; VandeHaar, M.; Lawlor, T.J.; Spurlock, D.M.; Armentano, L.E.; Staples, C.R.; Hanigan, M.; Haas, De Y.

    2016-01-01

    To include feed-intake-related traits in the breeding goal, accurate estimates of genetic parameters of feed intake, and its correlations with other related traits (i.e., production, conformation) are required to compare different options. However, the correlations between feed intake and

  11. Physical inactivity, depression, and risk of cardiovascular mortality

    NARCIS (Netherlands)

    Kamphuis, M.H.; Geerlings, M.I.; Tijhuis, M.A.R.; Giampaoli, S.; Nissinen, A.; Grobbee, D.E.; Kromhout, D.

    2007-01-01

    Purpose: Studies indicate that depression may increase risk of cardiovascular disease (CVD) in addition to classical risk factors. One of the hypotheses to explain this relation is that depressed subjects become physically inactive. We set out to determine the role of physical inactivity in the

  12. Estimating the burden of disease attributable to physical inactivity in ...

    African Journals Online (AJOL)

    Overall in adults 2 15 years in 2000, 30% of ischaemic heart disease, 27% of colon cancer, 22% of ischaemic stroke, 20% of type 2 diabetes, and 17% of breast cancer were attributable to physical inactivity. Physical inactivity was estimated to have caused 17 037 (95% uncertainty interval 11 394 - 20 407), or 3.3% (95% ...

  13. Physical inactivity and muscle oxidative capacity in humans

    DEFF Research Database (Denmark)

    Gram, Martin; Dahl, Rannvá; Dela, Flemming

    2014-01-01

    literature on the effects of different models of inactivity on muscle oxidative capacity in humans. Effects of physical inactivity include decreased mitochondrial content, decreased activity of oxidative enzymes, changes in markers of oxidative stress and a decreased expression of genes and contents...

  14. Physical inactivity and associated factors in chronic disease patients ...

    African Journals Online (AJOL)

    Physical inactivity and associated factors in chronic disease patients in Cambodia, Myanmar and Vietnam. ... Several factors were identified which may assist in programmes to promote physical activity in this population. Keywords: Physical inactivity, risk factors, chronic disease patients, Cambodia, Myanmar, Vietnam ...

  15. Conformal Aspects of QCD

    Energy Technology Data Exchange (ETDEWEB)

    Brodsky, S

    2003-11-19

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

  16. 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.

  17. Protein Conformational Plasticity: the 'off-on' Switching Movement in Cdk5

    International Nuclear Information System (INIS)

    Cavalli, Andrea; Recanatini, Maurizio; Berteotti, Anna; Branduardi, Davide; Gervasio, Francesco L.; Parrinello, Michele

    2007-01-01

    Cyclin-dependent kinases (CDKs) are mostly known for their role in the cell cycle regulation. The activation mechanism of all CDKs involves the association with a regulatory protein, generally a cyclin, that binds to the kinase unit and stabilizes a catalytically active conformation. Active and inactive conformations of CDKs are characterized by the different spatial localization of two typical elements, namely the activation loop and an □-helix, whose amino-acid composition varies throughout the family

  18. The Inactive Arctic Strategy of the United States

    Science.gov (United States)

    2012-02-15

    Gautier, David W. Houseknecht, Timothy R. Klett, Janet K. Pitman, Thomas E. Moore, Christopher J. Schenk, Marilyn E. Tennyson , and Craig J. Wandrey...Pitman, Thomas E. Moore, Christopher J. Schenk, Marilyn E. Tennyson , and Craig J. Wandrey. Circum-Arctic Resource Appraisal: Estimates of...R. Klett, Janet K. Pitman, Thomas E. Moore, Christopher J. Schenk, Marilyn E. Tennyson , and Craig J. Wandrey, 1; and O’Rourke, Ronald. Changes in

  19. The physical inactivity matrix: lessons from the classification of physical inactivity interventions.

    Science.gov (United States)

    Kypri, Kypros; Donaldson, Alex; Johnstone, Elizabeth

    2006-05-01

    Physical inactivity (PI), a leading modifiable cause of disease and injury, is endemic in industrialised nations. Although considerable research has been undertaken in this field, we lack a system to synthesise the research literature to inform policy and identify research needs. The aims of this study were to (1) develop a system to classify physical inactivity intervention studies, (2) examine the distribution of PI interventions published in the peer-reviewed health literature using the system, and (3) consider implications for future research. We developed the Physical Inactivity Matrix (PIM), with 12 intervention points, created by the intersection of two dimensions: the intervention target (individual, physical environment and social/cultural environment) and the activity focus (transport, work/school, leisure and consumer). A formal search of the health research literature identified 529 eligible studies and each was classified into one of the 12 cells of the PIM. Most studies were categorised as: individual-leisure (68%), individual-work/school (12%) or social/cultural environment-leisure (13%). Only 4% targeted the physical environment. The findings of this initial application of the PIM support the call for greater investment in policies, interventions and research that focus on the relationship between the environment and PI, and transportation in particular. There would be merit in establishing the inter-rater reliability of the PIM and applying it to a wider variety of studies, including those published in the transportation and urban planning literatures. The PIM could be a useful tool for monitoring trends in research directions and funding levels over time and across countries.

  20. 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....

  1. 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......-terminal alpha-helix was of major importance to the conformational stability of calreticulin....

  2. Physical inactivity, insulin resistance, and the oxidative-inflammatory loop.

    Science.gov (United States)

    Gratas-Delamarche, A; Derbré, F; Vincent, S; Cillard, J

    2014-01-01

    Epidemiological data indicate that physical inactivity, a main factor of global energetic imbalance, is involved in the worldwide epidemic of obesity and metabolic disorders such as insulin resistance. Although the complex pathogenesis of insulin resistance is not fully understood, literature data accumulated during the past decades clearly indicate that the activation of the oxidative-inflammatory loop plays a major role. By activating the oxidative-inflammatory loop in insulin-sensitive tissues, fat gain and adipose tissue dysfunction likely contribute to induce insulin resistance during chronic and prolonged physical inactivity. However, in the past years, evidence has emerged showing that early insulin resistance also occurs after very short-term exposure to physical inactivity (1-7 days) without any fat gain or energetic imbalance. The possible role of liver disturbances or endothelial dysfunction is suggested, but further studies are necessary to really conclude. Inactive skeletal muscle probably constitutes the primary triggering tissue for the development of early insulin resistance. In the present review, we discuss on the current knowledge about the effect of physical inactivity on whole-body and peripheral insulin sensitivity, and how local inflammation and oxidative stress arising with physical inactivity could potentially induce insulin resistance. We assume that early muscle insulin resistance allows the excess nutrients to shift in the storage tissues to withstand starvation through energy storage. We also consider when chronic and prolonged, physical inactivity over an extended period of time is an underestimated contributor to pathological insulin resistance and hence indirectly to numerous chronic diseases.

  3. Conformal invariance in supergravity

    International Nuclear Information System (INIS)

    Bergshoeff, E.A.

    1983-01-01

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

  4. Conformal supergravity in twistor-string theory

    Energy Technology Data Exchange (ETDEWEB)

    Berkovits, Nathan [Instituto de Fisica Teorica, Universidade Estadual Paulista, Rua Pamplona 145, 01405-900, Sao Paulo, SP (Brazil)]. E-mail: nberkovi@ift.unesp.br; Witten, Edward [School of Natural Sciences, Institute for Advanced Study, Princeton NJ 08540 (United States)

    2004-08-01

    Conformal supergravity arises in presently known formulations of twistor-string theory either via closed strings or via gauge-singlet open strings. We explore this sector of twistor-string theory, relating the relevant string modes to the particles and fields of conformal supergravity. We use the twistor-string theory to compute some tree level scattering amplitudes with supergravitons. Since the supergravitons interact with the same coupling constant as the Yang-Mills fields, conformal supergravity states will contribute to loop amplitudes of Yang-Mills gluons in these theories. Those loop amplitudes will therefore not coincide with the loop amplitudes of pure super Yang-Mills theory. (author)

  5. Conformal solids and holography

    Science.gov (United States)

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

    2017-12-01

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

  6. Conformal expansions and renormalons

    Energy Technology Data Exchange (ETDEWEB)

    Rathsman, J.

    2000-02-07

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

  7. Molecular determinants for drug-receptors Part 11. The preferred conformation of N-(p-anisoyl)pyrrolidin-2-one (``Aniracetam'') in the solid and solution states as indicated by X-ray crystal structure analysis, dipole moment and theoretical calculations

    Science.gov (United States)

    Bandoli, Giuliano; Nicolini, Marino; Lumbroso, Henri; Grassi, Antonio; Pappalardo, Giuseppe C.

    1987-09-01

    N-( p-anisoyl)pyrrolidin-2-one in the crystalline state exhibites a cis— rans conrotatory conformation with NCO and COC ar rotational angles of 33.5° and 38.5° respectively, and the p-methoxy group situated cis to the central carbonyl bond, as shown by X-ray structure analysis. As suggested by dipole moment analysis and MMP2 molecular mechanics calculations, in solution similar conrotatory models hold for both c- and t-subconformers having the p-methoxy group cis or trans to the central carbonyl bond. INDO calculations were also carried out, indicating that both subconformers are equally stable.

  8. Probing the Conformation of an IgG1 Monoclonal Antibody in Lyophilized Solids Using Solid-State Hydrogen-Deuterium Exchange with Mass Spectrometric Analysis (ssHDX-MS).

    Science.gov (United States)

    Moussa, Ehab M; Singh, Satish K; Kimmel, Michael; Nema, Sandeep; Topp, Elizabeth M

    2018-02-05

    Therapeutic proteins are often formulated as lyophilized products to improve their stability and prolong shelf life. The stability of proteins in the solid-state has been correlated with preservation of native higher order structure and/or molecular mobility in the solid matrix, with varying success. In the studies reported here, we used solid-state hydrogen-deuterium exchange with mass spectrometric analysis (ssHDX-MS) to study the conformation of an IgG1 monoclonal antibody (mAb) in lyophilized solids and related the extent of ssHDX to aggregation during storage in the solid phase. The results demonstrate that the extent of ssHDX correlated better with aggregation rate during storage than did solid-state Fourier-transform infrared (ssFTIR) spectroscopic measurements. Interestingly, adding histidine to sucrose at different formulation pH conditions decreased aggregation of the mAb, an effect that did not correlate with structural or conformational changes as measured by ssFTIR or ssHDX-MS. Moreover, peptide-level ssHDX-MS analysis in four selected formulations demonstrated global changes across the structure of the mAb when lyophilized with sucrose, trehalose, or mannitol, whereas site-specific changes were observed when lyophilized with histidine as the sole excipient.

  9. Recommendations and interventions to decrease physical inactivity at work

    NARCIS (Netherlands)

    Commissaris, D.; Douwes, M.

    2014-01-01

    Many contemporary work tasks, e.g. at an office workplace, are characterised by physical inactivity and by long periods of uninterrupted sitting. These characteristics increase the risk of several health problems, among others obesity, cardiovascular disorders, diabetes, cancer, musculoskeletal

  10. Impact of inactivity and exercise on the vasculature in humans.

    Science.gov (United States)

    Thijssen, Dick H J; Maiorana, Andrew J; O'Driscoll, Gerry; Cable, Nigel T; Hopman, Maria T E; Green, Daniel J

    2010-03-01

    The effects of inactivity and exercise training on established and novel cardiovascular risk factors are relatively modest and do not account for the impact of inactivity and exercise on vascular risk. We examine evidence that inactivity and exercise have direct effects on both vasculature function and structure in humans. Physical deconditioning is associated with enhanced vasoconstrictor tone and has profound and rapid effects on arterial remodelling in both large and smaller arteries. Evidence for an effect of deconditioning on vasodilator function is less consistent. Studies of the impact of exercise training suggest that both functional and structural remodelling adaptations occur and that the magnitude and time-course of these changes depends upon training duration and intensity and the vessel beds involved. Inactivity and exercise have direct "vascular deconditioning and conditioning" effects which likely modify cardiovascular risk.

  11. Chronic recreational physical inactivity and epithelial ovarian cancer risk

    DEFF Research Database (Denmark)

    Cannioto, Rikki; LaMonte, Michael J.; Risch, Harvey A

    2016-01-01

    , weekly recreational physical activity were classified as inactive. Multivariable logistic regression was utilized to estimate the ORs and 95% confidence intervals (CI) for the association between inactivity and EOC risk overall and by subgroups based upon histotype, menopausal status, race, and body mass......Background: Despite a large body of literature evaluating the association between recreational physical activity and epithelial ovarian cancer (EOC) risk, the extant evidence is inconclusive, and little is known about the independent association between recreational physical inactivity and EOC risk....... We conducted a pooled analysis of nine studies from the Ovarian Cancer Association Consortium to investigate the association between chronic recreational physical inactivity and EOC risk. Methods: In accordance with the 2008 Physical Activity Guidelines for Americans, women reporting no regular...

  12. Conformal and non conformal dilaton gravity

    Science.gov (United States)

    Alvarez, Enrique; Herrero-Valea, Mario; Martín, C. P.

    2014-10-01

    The quantum dynamics of the gravitational field non-minimally coupled to an (also dynamical) scalar field is studied in the broken phase. For a particular value of the coupling the system is classically conformal, and can actually be understood as the group averaging of Einstein-Hilbert's action under conformal transformations. Conformal invariance implies a simple Ward identity asserting that the trace of the equation of motion for the graviton is the equation of motion of the scalar field. We perform an explicit one-loop computation to show that the DeWitt effective action is not UV divergent on shell and to find that the Weyl symmetry Ward identity is preserved on shell at that level. We also discuss the fate of this Ward identity at the two-loop level — under the assumption that the two-loop UV divergent part of the effective action can be retrieved from the Goroff-Sagnotti counterterm — and show that its preservation in the renormalized theory requires the introduction of counterterms which exhibit a logarithmic dependence on the dilaton field.

  13. Radiation pathways and potential health impacts from inactive uranium mill tailings

    International Nuclear Information System (INIS)

    1978-07-01

    Radiation exposure pathways and potential health impacts were estimated as part of the evaluation of radioactive uranium mill tailings at the sites of inactive mills in eight western states. The purpose of this report is to describe in detail the methodology used in performing the pathway analysis and health effects estimations. In addition, specific parameters are presented for each of the 22 uranium mill sites that were evaluated. A computer program, RADAD, developed as part of this program, is described and listed

  14. PROFILE OF PHYSICAL INACTIVITY AS A RISK FACTOR

    OpenAIRE

    Sanjay; Ram C; Abhay; Vasant

    2014-01-01

    BACKGROUND: Eighty-five percent of the global burden of Non Communicable Diseases (NCD) is borne by the low and middle income countries, like India development. Emergence of NCDs in India is identified by WHO, ICMR and Government of India. NCDs share common risk factors like physical inactivity are causing 3.2 million deaths annually in the world (WHO, 2014). AIMS: Aim was to study profile of physical inactivity for non-communicable diseases. METHODS AND MATERIALS: SET...

  15. A stochastic model of protein conformational dynamics and electronic-conformational coupling in biological energy transduction

    Science.gov (United States)

    Cartling, Bo

    1985-11-01

    The principles of biological energy transduction are discussed by means of a mathematical model of a donor-acceptor system of electron transfer enzymes in which electronic and conformational states are coupled. The internal nuclear motion of the enzymes is considered to be composed of transitions between local potential energy wells, which define conformational states, and vibrations within these. The conformational transitions are treated as a stochastic process of the diffusion type on a conformational potential energy surface. Dissipative processes are avoided by restricting electron transfer with respect to conformational states and molecular mechanisms of such electron gating are discussed. Different types of transient kinetics, determined by the relative rates of electronic and conformational transitions, are demonstrated in terms of probability density functions, which describe the probability for the system to be in different electronic and conformational states as a function of time. The experimental basis for the concepts and mechanisms introduced is discussed and further experiments are proposed. The applicability of the mathematical model to other systems is indicated.

  16. 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.

  17. 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....

  18. Conformable variational iteration method

    Directory of Open Access Journals (Sweden)

    Omer Acan

    2017-02-01

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

  19. [Inactive dumps in Santa Catarina's carboniferous area: analysis of risks to the public health and the environment].

    Science.gov (United States)

    Possamai, Fernando Pagani; Viana, Ednilson; Schulz, Harry Edmar; de Costa, Marcel Madeira; Casagrande, Everson

    2007-01-01

    The existence of inactive dumps considerably increases the so-called "environmental liability"; so much so that the final destination of urban solid residues takes a prominent place on the list of environmental issues of societies(1). In the state of Santa Catarina, it can be said that, currently, the real conditions of the "final destination deposits", or simply the inactive dumps, is officially unknown. This is maybe most evident in the carboniferous area of the state that already suffers from the environmental impact of coal mining. This study attempts to make a survey of the inactive dumps in the carboniferous area of Santa Catarina, analysing the risks they represent to public health and to the environment. The results gathered show that, of the eleven municipal districts in the carboniferous area, nine have inactive dumps. In these nine districts, there are eleven inactive dumps that, according to the this evaluation, represent a large risk to public health and the environment when the parameters analysed are taken into acount.

  20. Experiential versus genetic accounts of inactivity: implications for inactive individuals' self-efficacy beliefs and intentions to exercise.

    Science.gov (United States)

    Beauchamp, Mark R; Rhodes, Ryan E; Kreutzer, Christiane; Rupert, James L

    2011-01-01

    The overall purpose of this study was to examine the effect of deterministic media reports, linking genetics to inactivity, in relation to inactive people's social cognitions concerning physical activity involvement. Sixty three inactive university students were randomly allocated to one of three experimental conditions (control, genetically-primed, experientially-primed) and completed measures of instrumental and affective attitudes, subjective norms, self-efficacy, and exercise intentions. One week later participants in the two experimental conditions were provided with a bogus newspaper report that either reflected a genetic explanation for physical inactivity or an experiential basis for inactivity. Shortly afterwards, participants in all three conditions completed the same measures as at pre-test. The results revealed that after controlling for baseline measures participants in the experientially-primed condition reported significantly higher levels of self-efficacy and intentions to exercise than those in the genetically-primed condition. These findings raise a cautionary flag concerning the presentation of genetic research in the media, especially with regard to inactive populations.

  1. Conformational kinetics of aliphatic tails

    Science.gov (United States)

    Ferrarini, Alberta; Moro, Giorgio; Nordio, Pier Luigi

    The master equation describing the random walk between sites identified with the stable conformers of a chain molecule, represents the extension to the time domain of the Rotational Isomeric State model. The asymptotic analysis of the multidimensional diffusion equation in the continuous torsional variables subjected to the configurational potential, provides a rigorous justification for the discrete models, and it supplies, without resorting to phenomenological parameters, molecular definitions of the kinetic rates for the conformational transitions occurring at each segment of the chain. The coupling between the torsional variables is fully taken into account, giving rise to cooperative effects. A complete calculation of the specific correlation functions which describe the time evolution of the angular functions probed by N.M.R. and dielectric relaxation measurements, has been performed for alkyl chains attached to a massive core. The resulting behaviour has been compared with the decay of trans and gauche populations of specific bonds, expressed in terms of suitable correlation functions whose time integrals lead quite naturally to the definition of effective kinetic constants for the conformational transitions.

  2. A probabilistic model of RNA conformational space

    DEFF Research Database (Denmark)

    Frellsen, Jes; Moltke, Ida; Thiim, Martin

    2009-01-01

    The increasing importance of non-coding RNA in biology and medicine has led to a growing interest in the problem of RNA 3-D structure prediction. As is the case for proteins, RNA 3-D structure prediction methods require two key ingredients: an accurate energy function and a conformational sampling...... procedure. Both are only partly solved problems. Here, we focus on the problem of conformational sampling. The current state of the art solution is based on fragment assembly methods, which construct plausible conformations by stringing together short fragments obtained from experimental structures. However...... efficient sampling of RNA conformations in continuous space, and with associated probabilities. We show that the model captures several key features of RNA structure, such as its rotameric nature and the distribution of the helix lengths. Furthermore, the model readily generates native-like 3-D...

  3. Social conformity despite individual preferences for distinctiveness.

    Science.gov (United States)

    Smaldino, Paul E; Epstein, Joshua M

    2015-03-01

    We demonstrate that individual behaviours directed at the attainment of distinctiveness can in fact produce complete social conformity. We thus offer an unexpected generative mechanism for this central social phenomenon. Specifically, we establish that agents who have fixed needs to be distinct and adapt their positions to achieve distinctiveness goals, can nevertheless self-organize to a limiting state of absolute conformity. This seemingly paradoxical result is deduced formally from a small number of natural assumptions and is then explored at length computationally. Interesting departures from this conformity equilibrium are also possible, including divergence in positions. The effect of extremist minorities on these dynamics is discussed. A simple extension is then introduced, which allows the model to generate and maintain social diversity, including multimodal distinctiveness distributions. The paper contributes formal definitions, analytical deductions and counterintuitive findings to the literature on individual distinctiveness and social conformity.

  4. Prevalence and factors associated with physical inactivity among Malaysian adults.

    Science.gov (United States)

    Ying, Chanying; Kuay, Lim Kuang; Huey, Teh Chien; Hock, Lim Kuang; Hamid, Hamizatul Akmal Abd; Omar, Mohd Azahadi; Ahmad, Noor Ani; Cheong, Kee Chee

    2014-03-01

    Using data from the Third National Health and Morbidity Survey (NHMS III) in 2006, this study examined the association between socio-demographic factors and physical inactivity in a sample of 33,949 adults aged 18 years and above by gender. Physical activity levels were measured using the Global Physical Activity Questionnaire (GPAQ vers 1). Physical inactivity was defined as having a total physical activity level of less than 600 metabolic equivalents-minutes per week (METs-minutes/week) contributed by all three different life domains.Logistic regression analyses were conducted.The prevalence of overall physical inactivity was 43.7% (95% CI: 42.9-44.5). The mean total physical activity level was 894.2 METs-minutes/ week. The means METs-minutes/week for the domain of work, travelling, and leisure time were 518.4, 288.1, and 134.8, respectively. Multivariable logistic regression analyses indicated that females were more likely to be physically inactive than males were (aOR=1.62; 95% CI: 1.53-1.72). Among women, being a housewife (aOR = 1.78; 95% CI: 1.56-2.03), widow/divorcee (aOR = 1.23; 95% CI: 1.05-1.43), and those with no formal education (aOR = 1.20; 95% CI: 1.01-1.43) were found to be significantly associated with physical inactivity.Urban residents, older adults aged 65 years and above, private employees, nonworking group, and those with a monthly household income level of MYR5,000 and above appeared to be consistently associated with physical inactivity across men, women, and combined group (both). Specific health intervention strategies to promote physical activity should be targeted on population subgroups who are inactive.

  5. MAR elements regulate the probability of epigenetic switching between active and inactive gene expression.

    Science.gov (United States)

    Galbete, José Luis; Buceta, Montserrat; Mermod, Nicolas

    2009-02-01

    Gene expression often cycles between active and inactive states in eukaryotes, yielding variable or noisy gene expression in the short-term, while slow epigenetic changes may lead to silencing or variegated expression. Understanding how cells control these effects will be of paramount importance to construct biological systems with predictable behaviours. Here we find that a human matrix attachment region (MAR) genetic element controls the stability and heritability of gene expression in cell populations. Mathematical modeling indicated that the MAR controls the probability of long-term transitions between active and inactive expression, thus reducing silencing effects and increasing the reactivation of silent genes. Single-cell short-terms assays revealed persistent expression and reduced expression noise in MAR-driven genes, while stochastic burst of expression occurred without this genetic element. The MAR thus confers a more deterministic behavior to an otherwise stochastic process, providing a means towards more reliable expression of engineered genetic systems.

  6. Revegetation and rock cover for stabilization of inactive uranium mill tailings disposal sites. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Beedlow, P.A.

    1984-05-01

    Guidelines for using vegetation and rock to protect inactive uranium mill tailings from erosion were developed by Pacific Northwest Laboratory as part of the Department of Energy's Uranium Mill Tailings Remedial Action Project (UMTRAP) Technology Development program. Information on soils, climate, and vegetation were collected for 20 inactive tailings sites in the western United States. Sites were grouped according to similarities in climate and vegetation. Soil loss for those sites was characterized using the Universal Soil Loss Equation. Test plots were used to evaluate (1) the interaction between vegetation and sealant barrier systems and (2) the effects of surface rock on soil water and vegetation. Lysimeter and simulation studies were used to direct and support field experiments. 49 references, 17 figures, 16 tables.

  7. Revegetation and rock cover for stabilization of inactive uranium mill tailings disposal sites. Final report

    International Nuclear Information System (INIS)

    Beedlow, P.A.

    1984-05-01

    Guidelines for using vegetation and rock to protect inactive uranium mill tailings from erosion were developed by Pacific Northwest Laboratory as part of the Department of Energy's Uranium Mill Tailings Remedial Action Project (UMTRAP) Technology Development program. Information on soils, climate, and vegetation were collected for 20 inactive tailings sites in the western United States. Sites were grouped according to similarities in climate and vegetation. Soil loss for those sites was characterized using the Universal Soil Loss Equation. Test plots were used to evaluate (1) the interaction between vegetation and sealant barrier systems and (2) the effects of surface rock on soil water and vegetation. Lysimeter and simulation studies were used to direct and support field experiments. 49 references, 17 figures, 16 tables

  8. Asymptotic mass degeneracies in conformal field theories

    International Nuclear Information System (INIS)

    Kani, I.; Vafa, C.

    1990-01-01

    By applying a method of Hardy and Ramanujan to characters of rational conformal field theories, we find an asymptotic expansion for degeneracy of states in the limit of large mass which is exact for strings propagating in more than two uncompactified space-time dimensions. Moreover we explore how the rationality of the conformal theory is reflected in the degeneracy of states. We also consider the one loop partition function for strings, restricted to physical states, for arbitrary (irrational) conformal theories, and obtain an asymptotic expansion for it in the limit that the torus degenerates. This expansion depends only on the spectrum of (physical and unphysical) relevant operators in the theory. We see how rationality is consistent with the smoothness of mass degeneracies as a function of moduli. (orig.)

  9. Mortality and years of life lost by colorectal cancer attributable to physical inactivity in Brazil (1990-2015): Findings from the Global Burden of Disease Study.

    Science.gov (United States)

    Silva, Diego Augusto Santos; Tremblay, Mark Stephen; Souza, Maria de Fatima Marinho de; Mooney, Meghan; Naghavi, Mohsen; Malta, Deborah Carvalho

    2018-01-01

    The aims of this study were to estimate all-cause and cause-specific mortality and years of life lost, investigated by disability-adjusted life-years (DALYs), due to colorectal cancer attributable to physical inactivity in Brazil and in the states; to analyze the temporal trend of these estimates over 25 years (1990-2015) compared with global estimates and according to the socioeconomic status of states of Brazil. Databases from the Global Burden of Disease Study (GBD) for Brazil, Brazilian states and global information were used. It was estimated the total number and the age-standardized rates of deaths and DALYs for colorectal cancer attributable to physical inactivity in the years 1990 and 2015. We used the Socioeconomic Development Index (SDI). Physical inactivity was responsible for a substantial number of deaths (1990: 1,302; 2015: 119,351) and DALYs (1990: 31,121; 2015: 87,116) due to colorectal cancer in Brazil. From 1990 to 2015, the mortality and DALYs due to colorectal cancer attributable to physical inactivity increased in Brazil (0.6% and 0.6%, respectively) and decreased around the world (-0.8% and -1.1%, respectively). The Brazilian states with better socioeconomic indicators had higher rates of mortality and morbidity by colorectal cancer due to physical inactivity (pBrazil. Over 25 years, the Brazilian population showed more worrisome results than around the world. Actions to combat physical inactivity and greater cancer screening and treatment are urgent in the Brazilian states.

  10. Conformal invariance of curvature perturbation

    CERN Document Server

    Gong, Jinn-Ouk; Park, Wan Il; Sasaki, Misao; Song, Yong-Seon

    2011-01-01

    We show that in the single component situation all perturbation variables in the comoving gauge are conformally invariant to all perturbation orders. Generally we identify a special time slicing, the uniform-conformal transformation slicing, where all perturbations are again conformally invariant to all perturbation orders. We apply this result to the delta N formalism, and show its conformal invariance.

  11. Solid-state structure and solution conformation of the nootropic agent N[2-( N,N-Diisopropylamino)ethyl]-2-oxo-1-pyrrolidinacetamide sulphate. X-ray and homonuclear two-dimensional 1H NMR studies

    Science.gov (United States)

    Bandoli, Giuliano; Nicolini, Marino; Pappalardo, Giuseppe C.; Grassi, Antonio; Perly, Bruno

    1987-04-01

    The crystal and molecular structure of the nootropic agent N-[2-( N,N-diisopropyl-amino)ethyl]-2-oxo-1-pyrrolidinacetamide sulphate was determined by X-ray analysis. The conformational properties in the solution state were deduced from the 1H-NMR spectrum run in 2H 2O at 500 MHz. Spectral assignments were made with the aid of the COSY 45 shift correlation experiment. Crystals were triclinic with unit cell dimensions a = 13.410(10), b = 11.382(8), c = 6.697(4) », α = 83.80(3), β = 88.61(3)and γ = 72.25(6)° ; space group Poverline1. The structure was determined from 1047 three-dimensional counter data and refined to a value of 7.5% for the conventional discrepancy factor R. One molecule of the solvent acetonitrile is incorporated per two of the (C 14H 28N 3O 2) +-(HSO 4) -. The five-membered heterocyclic ring is in an envelope ( Cs) conformation and the "flap" atom deviates by 0.31 » from the plane of the other four. This plane forms a dihedral angle of 71.4° with the amide group, with the CO fragment directed toward the ring. All bond angles and distances are in good agreement with expected standard values. A strong OH⋯O intermolecular bond (2.61 ») links the cation of the hydrogen-sulphate anion, while the loosely held MeCN molecule is trapped in the polar pockets. The molecular conformation in the solid was compared with results from 1H NMR spectral analysis which showed that in solution wide torsional oscillations can occur about the bonds of the chain bonded to the N(1) atom.

  12. Conformity and statistical tolerancing

    Science.gov (United States)

    Leblond, Laurent; Pillet, Maurice

    2018-02-01

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

  13. An Engineered Disulfide Bond Reversibly Traps the IgE-Fc3-4 in a Closed, Nonreceptor Binding Conformation

    Energy Technology Data Exchange (ETDEWEB)

    Wurzburg, Beth A.; Kim, Beomkyu; Tarchevskaya, Svetlana S.; Eggel, Alexander; Vogel, Monique; Jardetzky, Theodore S. [Bern; (Stanford-MED)

    2013-08-02

    IgE antibodies interact with the high affinity IgE Fc receptor, FcϵRI, and activate inflammatory pathways associated with the allergic response. The IgE-Fc region, comprising the C-terminal domains of the IgE heavy chain, binds FcϵRI and can adopt different conformations ranging from a closed form incompatible with receptor binding to an open, receptor-bound state. A number of intermediate states are also observed in different IgE-Fc crystal forms. To further explore this apparent IgE-Fc conformational flexibility and to potentially trap a closed, inactive state, we generated a series of disulfide bond mutants. Here we describe the structure and biochemical properties of an IgE-Fc mutant that is trapped in the closed, non-receptor binding state via an engineered disulfide at residue 335 (Cys-335). Reduction of the disulfide at Cys-335 restores the ability of IgE-Fc to bind to its high affinity receptor, FcϵRIα. The structure of the Cys-335 mutant shows that its conformation is within the range of previously observed, closed form IgE-Fc structures and that it retains the hydrophobic pocket found in the hinge region of the closed conformation. Locking the IgE-Fc into the closed state with the Cys-335 mutation does not affect binding of two other IgE-Fc ligands, omalizumab and DARPin E2_79, demonstrating selective blocking of the high affinity receptor binding.

  14. Algebraic conformal field theory

    International Nuclear Information System (INIS)

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

    1991-11-01

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

  15. Solution- and solid-state conformations of C(α)-alkyl analogues of methylphenidate (Ritalin) salts: avoidance of gauche(+)gauche(-) interactions.

    Science.gov (United States)

    Steinberg, Avital; Froimowitz, Mark; Parrish, Damon A; Deschamps, Jeffrey R; Glaser, Robert

    2011-11-18

    Alkyl analogues of methylphenidate (Ritalin) salts are slow onset, long duration dopamine reuptake inhibitors with a potential use as a cocaine abuse pharmacotherapy. X-ray crystallographic studies and nuclear magnetic resonance (NMR) investigations strongly suggest that avoidance of sterically unfavorable gauche(-)gauche(+) orientations effectively influences both the C(α)-alkyl side chain conformation and the formation of a predominant rotamer about the CH-CH bond ligating piperidine and C(Ar)R moieties. The favored CH-CH rotamer in D(2)O and in CD(2)Cl(2) of the pharmacologically interesting i-Bu and CH(2)-cyc-Pnt (RS,RS)-salts has the same antiperiplanar arrangement that was found in the crystal structures, although there clearly is a fast equilibrium involving smaller amounts of synclinal partners. While the rotamer in the (RS,SR)-i-Bu HCl crystal structure exhibits a synclinal orientation for the vicinal pair of adjacent methine protons, the weighted time-averaged arrangement for these protons becomes almost completely antiperiplanar when the crystals are dissolved in D(2)O. Increased steric congestion around the CH-CH bond in the analogous N-methyl tertiary ammonium salts seems to augment the quantity of the preferred rotamer within the mixture. The stereochemistry of the species observed via NMR seems to arise from specific combinations of N-methyl orientation and avoidance of sterically unfavorable gauche(-)gauche(+) arrangements.

  16. Jarid2 Is Implicated in the Initial Xist-Induced Targeting of PRC2 to the Inactive X Chromosome

    DEFF Research Database (Denmark)

    da Rocha, Simão Teixeira; Boeva, Valentina; Escamilla-Del-Arenal, Martin

    2014-01-01

    During X chromosome inactivation (XCI), the Polycomb Repressive Complex 2 (PRC2) is thought to participate in the early maintenance of the inactive state. Although Xist RNA is essential for the recruitment of PRC2 to the X chromosome, the precise mechanism remains unclear. Here, we demonstrate...

  17. Killing tensors and conformal Killing tensors from conformal Killing vectors

    International Nuclear Information System (INIS)

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

    2003-01-01

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

  18. Inactive Doses and Protein Concentration of Gamma Irradiated Yersinia Enterocolitica

    International Nuclear Information System (INIS)

    Irawan Sugoro; Sandra Hermanto

    2009-01-01

    Yersinia enterocolitica is one of bacteria which cause coliform mastitis in dairy cows. The bacteria could be inactivated by gamma irradiation as inactivated vaccine candidate. The experiment has been conducted to determine the inactive doses and the protein concentration of Yersinia enterocolitica Y3 which has been irradiated by gamma rays. The cells cultures were irradiated by gamma rays with doses of 0, 100, 200, 400, 600, 800, 1.000 and 1.500 Gy (doses rate was 1089,59 Gy/hours). The inactive dose was determined by the drop test method and the protein concentration of cells were determined by Lowry method. The results showed that the inactive doses occurred on 800 – 1500 Gy. The different irradiation doses of cell cultures showed the effect of gamma irradiation on the protein concentration that was random and has a significant effect on the protein concentration. (author)

  19. Assessing compliance: Active versus inactive trainees in a memory intervention

    Directory of Open Access Journals (Sweden)

    Dana K Bagwell

    2008-06-01

    Full Text Available Dana K Bagwell, Robin L WestDepartment of Psychology, University of Florida, Gainesville, FL, USAAbstract: Extensive research on memory interventions has confirmed their success with older adults, but the individual difference factors that predict successful training outcomes remain relatively unexplored. In the current intervention, trainees were identified as active (compliant with training regimens or inactive using trainer ratings based on attendance, homework completion, and class participation. The active group showed significantly greater training-related gains than the inactive group and the control group on most measures. Compliance was predicted by health, education, and self-efficacy. Specifically, active trainees were more likely to have advanced degrees and somewhat higher self-efficacy, and to have higher vitality and fewer functional limitations than the inactive trainees. This research may assist future investigators to target interventions to those who will show the most benefit.Keywords: compliance, memory training, aging, intervention

  20. Environmental condition and impact of inactive uranium mines

    International Nuclear Information System (INIS)

    Hans, J.M. Jr.; Eadie, G.E.; O'Connell, M.F.

    1981-01-01

    The US Environmental Protection Agency (EPA) was required to provide a report to Congress identifying the location, and potential health, safety and environmental hazards of uranium mine wastes together with recommendations, if any, for a program to eliminate the hazards. The approach taken to prepare this report was to develop model active and inactive mines and locate them in a typical mining area to estimate their environmental impact. The inactive mines were separated from the list and sorted into surface and underground categories. A literature search was conducted to obtain and consolidate available information concerning the environmental aspects of uranium mining and short-term field surveys and studies were conducted to augment this information base. Radioactivity emission rates were measured or estimated for each mining category and were entered into computer codes to assess population exposures and subsequent health risks. The general environmental condition of inactive uranium mines was determined by walk-through surveys in several mining areas

  1. A model for predicting Inactivity in the European Banking Sector

    Directory of Open Access Journals (Sweden)

    Themistokles Lazarides

    2015-08-01

    Full Text Available Purpose – The paper will addresses the issue of inactivity and will try to detect its causes using econometric models. The Banking sector of Europe has been under transformation or restructuring for almost half a century. Design/methodology/approach – Probit models and descriptive statistics have been used to create a system that predicts inactivity. The data was collected from Bankscope. Findings – The results of the econometric models show that from the six groups of indicators, four have been found to be statistically important (performance, size, ownership, corporate governance. These findings are consistent with the theory. Research limitations/implications – The limitation is that Bankscope does not provide any longitudinal data regarding ownership, management structure and there are some many missing values before 2007 for some of the financial ratios and data. Originality/value – The paper's value and innovation is that it has given a systemic approach to find indicators of inactivity.

  2. Charged conformal Killing spinors

    Energy Technology Data Exchange (ETDEWEB)

    Lischewski, Andree, E-mail: lischews@mathematik.hu-berlin.de [Humboldt-Universität zu Berlin, Institut für Mathematik, Rudower Chaussee 25, Room 1.310, D12489 Berlin (Germany)

    2015-01-15

    We study the twistor equation on pseudo-Riemannian Spin{sup c}-manifolds whose solutions we call charged conformal Killing spinors (CCKSs). We derive several integrability conditions for the existence of CCKS and study their relations to spinor bilinears. A construction principle for Lorentzian manifolds admitting CCKS with nontrivial charge starting from CR-geometry is presented. We obtain a partial classification result in the Lorentzian case under the additional assumption that the associated Dirac current is normal conformal and complete the classification of manifolds admitting CCKS in all dimensions and signatures ≤5 which has recently been initiated in the study of supersymmetric field theories on curved space.

  3. 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

  4. Substrate Capture Assay Using Inactive Oligopeptidases to Identify Novel Peptides.

    Science.gov (United States)

    Rioli, Vanessa; Ferro, Emer S

    2018-01-01

    Researchers are always searching for novel biologically active molecules including peptides. With the improvement of equipment for electrospray mass spectrometry, it is now possible to identify hundreds of novel peptides in a single run. However, after identifying the peptide sequences it is expensive to synthesize all the peptides to perform biological activity assays. Here, we describe a substrate capture assay that uses inactive oligopeptidases to identify putative biologically active peptides in complexes peptide mixtures. This methodology can use any crude extracts of biological tissues or cells, with the advantage to introduce a filter (i.e., binding to an inactive oligopeptidase) as a prior step in screening to bioactive peptides.

  5. The economic benefits of reducing physical inactivity: an Australian example.

    Science.gov (United States)

    Cadilhac, Dominique A; Cumming, Toby B; Sheppard, Lauren; Pearce, Dora C; Carter, Rob; Magnus, Anne

    2011-09-24

    Physical inactivity has major impacts on health and productivity. Our aim was to estimate the health and economic benefits of reducing the prevalence of physical inactivity in the 2008 Australian adult population. The economic benefits were estimated as 'opportunity cost savings', which represent resources utilized in the treatment of preventable disease that are potentially available for re-direction to another purpose from fewer incident cases of disease occurring in communities. Simulation models were developed to show the effect of a 10% feasible, reduction target for physical inactivity from current Australian levels (70%). Lifetime cohort health benefits were estimated as fewer incident cases of inactivity-related diseases; deaths; and Disability Adjusted Life Years (DALYs) by age and sex. Opportunity costs were estimated as health sector cost impacts, as well as paid and unpaid production gains and leisure impacts from fewer disease events associated with reduced physical inactivity. Workforce production gains were estimated by comparing surveyed participation and absenteeism rates of physically active and inactive adults, and valued using the friction cost approach. The impact of an improvement in health status on unpaid household production and leisure time were modeled from time use survey data, as applied to the exposed and non-exposed population subgroups and valued by suitable proxy. Potential costs associated with interventions to increase physical activity were not included. Multivariable uncertainty analyses and univariate sensitivity analyses were undertaken to provide information on the strength of the conclusions. A 10% reduction in physical inactivity would result in 6,000 fewer incident cases of disease, 2,000 fewer deaths, 25,000 fewer DALYs and provide gains in working days (114,000), days of home-based production (180,000) while conferring a AUD96 million reduction in health sector costs. Lifetime potential opportunity cost savings in

  6. The economic benefits of reducing physical inactivity: an Australian example

    Directory of Open Access Journals (Sweden)

    Cumming Toby B

    2011-09-01

    Full Text Available Abstract Background Physical inactivity has major impacts on health and productivity. Our aim was to estimate the health and economic benefits of reducing the prevalence of physical inactivity in the 2008 Australian adult population. The economic benefits were estimated as 'opportunity cost savings', which represent resources utilized in the treatment of preventable disease that are potentially available for re-direction to another purpose from fewer incident cases of disease occurring in communities. Methods Simulation models were developed to show the effect of a 10% feasible, reduction target for physical inactivity from current Australian levels (70%. Lifetime cohort health benefits were estimated as fewer incident cases of inactivity-related diseases; deaths; and Disability Adjusted Life Years (DALYs by age and sex. Opportunity costs were estimated as health sector cost impacts, as well as paid and unpaid production gains and leisure impacts from fewer disease events associated with reduced physical inactivity. Workforce production gains were estimated by comparing surveyed participation and absenteeism rates of physically active and inactive adults, and valued using the friction cost approach. The impact of an improvement in health status on unpaid household production and leisure time were modeled from time use survey data, as applied to the exposed and non-exposed population subgroups and valued by suitable proxy. Potential costs associated with interventions to increase physical activity were not included. Multivariable uncertainty analyses and univariate sensitivity analyses were undertaken to provide information on the strength of the conclusions. Results A 10% reduction in physical inactivity would result in 6,000 fewer incident cases of disease, 2,000 fewer deaths, 25,000 fewer DALYs and provide gains in working days (114,000, days of home-based production (180,000 while conferring a AUD96 million reduction in health sector costs

  7. Focused conformational sampling in proteins

    Science.gov (United States)

    Bacci, Marco; Langini, Cassiano; Vymětal, Jiří; Caflisch, Amedeo; Vitalis, Andreas

    2017-11-01

    A detailed understanding of the conformational dynamics of biological molecules is difficult to obtain by experimental techniques due to resolution limitations in both time and space. Computer simulations avoid these in theory but are often too short to sample rare events reliably. Here we show that the progress index-guided sampling (PIGS) protocol can be used to enhance the sampling of rare events in selected parts of biomolecules without perturbing the remainder of the system. The method is very easy to use as it only requires as essential input a set of several features representing the parts of interest sufficiently. In this feature space, new states are discovered by spontaneous fluctuations alone and in unsupervised fashion. Because there are no energetic biases acting on phase space variables or projections thereof, the trajectories PIGS generates can be analyzed directly in the framework of transition networks. We demonstrate the possibility and usefulness of such focused explorations of biomolecules with two loops that are part of the binding sites of bromodomains, a family of epigenetic "reader" modules. This real-life application uncovers states that are structurally and kinetically far away from the initial crystallographic structures and are also metastable. Representative conformations are intended to be used in future high-throughput virtual screening campaigns.

  8. CHANGES IN MENTAL HEALTH AND SATISFACTION WITH LIFE DURING PHYSICAL INACTIVITY INDUCED BY BED REST EXPERIMENT

    Directory of Open Access Journals (Sweden)

    Tjaša Dimec Časar

    2016-01-01

    Full Text Available Simulated weightlessness by bed rest model represents an important method to study the consequences of physical inactivity and sedentarism on the human body. The purpose of the study was to examine the effects of prolonged physical inactivity on psychological distress, depressive symptoms and satisfaction with life of healthy male adults. Participants were ten volunteers, aged between 21 and 28 years who were subjected to a 35-day head-down bed rest. Psychological state of the participants was measured with the General Health Questionnaire (GHQ-12, the Center for Epidemiological Studies Depression Scale (CES-D, and the Satisfaction with Life Scale (SWLS. Participants completed psychological inventories before, during and after the experiment. The results revealed no significant differences in mental health and satisfaction with life of participants following the head-down bed rest, however there was a tendency towards an increase in neurotic and depressive symptoms at the end of the experiment. The obtained results are interpreted in the light of stimulative living conditions in which the experiment was carried out, as well as the amount and quality of social interactions during the period of extended physical inactivity.

  9. Conformational properties of pyrethroids

    Science.gov (United States)

    Mullaley, Anne; Taylor, Robin

    1994-04-01

    X-ray database searches and theoretical potential-energy calculations indicate that the acid moieties of pyrethroid cyclopropanecarboxylate esters adopt a well-defined, relatively inflexible conformation. In contrast, the alcohol moieties can exist in many low-energy geometries. One of the least conformationally flexible pyrethroid alcohols is 4-phenylindan-2-ol. The approximate overall conformation adopted at the biological binding site by insecticidal esters of this alcohol can be deduced with reasonable confidence by molecular modelling. Graphics superposition of a variety of pyrethroid acids suggests the existence of a large but rather narrow pocket at the binding site, in which substituents at the 3-position of the cyclopropane ring can be accommodated. This pocket is asymmetric with respect to the plane of the cyclopropane ring, extending further on the side remote from the ester group. The effects of α-substitution on the insecticidal activity of pyrethroid esters may be due to the influence of substituents on the preferred conformations of the molecules. This hypothesis rationalises the paradoxical dependence on absolute stereochemistry of the activities of various allylbenzyl and cinnamyl alcohol derivatives.

  10. Conformal special relativity

    International Nuclear Information System (INIS)

    Maia, M.D.

    2006-01-01

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

  11. Animal culture: chimpanzee conformity?

    Science.gov (United States)

    van Schaik, Carel P

    2012-05-22

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

  12. Conformal Dirac structures

    International Nuclear Information System (INIS)

    Wade, A.

    2000-07-01

    The Courant bracket defined originally on the sections of a vector bundle TM +T*M → M is extended to the direct sum of the 1-jet vector bundle and its dual. The extended bracket allows one to interpret many structures encountered in differential geometry, in terms of Dirac structures. We give a new approach to conformal Jacobi structures. (author)

  13. Physical Inactivity as a Predictor of High Prevalence of Hypertension ...

    African Journals Online (AJOL)

    Logistic and multiple linear regression models were used to calculate the risk of prevalent hypertension in physically inactive individuals and examine the association between physical activity and healthcare expenditure after controlling for confounders. Results: Hypertensive patients who were physically active accounted ...

  14. Physical Inactivity, Obesity, and Type 2 Diabetes: An Evolutionary Perspective

    Science.gov (United States)

    Eaton, S. Boyd; Eaton, Stanley B.

    2017-01-01

    Physical inactivity (and unhealthy nutrition) has distorted body composition and, in turn, reordered the proportions of myocyte and adipocyte insulin receptors. Insulin acting on adipocyte receptors produces less glucose uptake than does comparable interaction with myocyte receptors. Accordingly, in individuals with disproportionate muscle/fat…

  15. Motor proficiency and physical fitness in active and inactive girls ...

    African Journals Online (AJOL)

    In modern day society physical activity levels diminish rapidly among girls and may be a direct consequence of girls experiencing motor difficulties. Therefore the aim of the study was to compare motor proficiency levels and physical fitness levels among active and inactive girls (N=97), aged 12 to 13 years. The BOTMP ...

  16. Prevalence, social and health correlates of physical inactivity among ...

    African Journals Online (AJOL)

    Individuals who had high social capital (OR: 0.69, CI: 0.60, 0.79) were less likely to be physically inactive than those with low social capital. Several sociodemographic (older age, female, higher education and urban residence) and health risk (such as overweight, weak grip strength, functional disability, and low fruit and ...

  17. The Body Image Of Physically Active And Inactive Women

    Directory of Open Access Journals (Sweden)

    Guszkowska Monika

    2015-06-01

    Full Text Available Introduction. The aim of the study was to compare the image of the body, the level of its acceptance and satisfaction with it, as well as anxiety about one’s physical appearance and overall self-esteem in a group of adult women who did fitness exercise and those who were physically inactive.

  18. Automatic Detection of Inactive Solar Cell Cracks in Electroluminescence Images

    DEFF Research Database (Denmark)

    Spataru, Sergiu; Hacke, Peter; Sera, Dezso

    2017-01-01

    We propose an algorithm for automatic determination of the electroluminescence (EL) signal threshold level corresponding to inactive solar cell cracks, resulting from their disconnection from the electrical circuit of the cell. The method enables automatic quantification of the cell crack size an...

  19. Effects of probiotic (live and inactive Saccharomyces cerevisiae ) on ...

    African Journals Online (AJOL)

    The present work evaluated the effect of probiotic (live and inactive Saccharomyces cerevisiae) on meat and intestinal microbial properties of Japanese quails. Twenty-four (24) 1-day-old Japanese quails were obtained from a commercial hatchery. The birds were randomly divided into 2 groups. The dietary treatments ...

  20. Muscle activity and inactivity periods during normal daily life.

    Directory of Open Access Journals (Sweden)

    Olli Tikkanen

    Full Text Available Recent findings suggest that not only the lack of physical activity, but also prolonged times of sedentary behaviour where major locomotor muscles are inactive, significantly increase the risk of chronic diseases. The purpose of this study was to provide details of quadriceps and hamstring muscle inactivity and activity during normal daily life of ordinary people. Eighty-four volunteers (44 females, 40 males, 44.1±17.3 years, 172.3±6.1 cm, 70.1±10.2 kg were measured during normal daily life using shorts measuring muscle electromyographic (EMG activity (recording time 11.3±2.0 hours. EMG was normalized to isometric MVC (EMG(MVC during knee flexion and extension, and inactivity threshold of each muscle group was defined as 90% of EMG activity during standing (2.5±1.7% of EMG(MVC. During normal daily life the average EMG amplitude was 4.0±2.6% and average activity burst amplitude was 5.8±3.4% of EMG(MVC (mean duration of 1.4±1.4 s which is below the EMG level required for walking (5 km/h corresponding to EMG level of about 10% of EMG(MVC. Using the proposed individual inactivity threshold, thigh muscles were inactive 67.5±11.9% of the total recording time and the longest inactivity periods lasted for 13.9±7.3 min (2.5-38.3 min. Women had more activity bursts and spent more time at intensities above 40% EMG(MVC than men (p<0.05. In conclusion, during normal daily life the locomotor muscles are inactive about 7.5 hours, and only a small fraction of muscle's maximal voluntary activation capacity is used averaging only 4% of the maximal recruitment of the thigh muscles. Some daily non-exercise activities such as stair climbing produce much higher muscle activity levels than brisk walking, and replacing sitting by standing can considerably increase cumulative daily muscle activity.

  1. 40 CFR 93.161 - Conformity evaluation for Federal installations with facility-wide emission budgets.

    Science.gov (United States)

    2010-07-01

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

  2. 47 CFR 1.1904 - Conformance to law and regulations.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 1 2010-10-01 2010-10-01 false Conformance to law and regulations. 1.1904... Collection of Claims Owed the United States General Provisions § 1.1904 Conformance to law and regulations. The requirements of applicable law (31 U.S.C. 3701-3719, as amended by Public Law 97-365, 96 Stat...

  3. 29 CFR 1450.4 - Conformance to law and regulations.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 4 2010-07-01 2010-07-01 false Conformance to law and regulations. 1450.4 Section 1450.4 Labor Regulations Relating to Labor (Continued) FEDERAL MEDIATION AND CONCILIATION SERVICE COLLECTIONS OF CLAIMS OWED THE UNITED STATES General Provisions § 1450.4 Conformance to law and regulations. The...

  4. 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....

  5. Variation in the Gender Gap in Inactive and Active Life Expectancy by the Definition of Inactivity Among Older Adults.

    Science.gov (United States)

    Malhotra, Rahul; Chan, Angelique; Ajay, Shweta; Ma, Stefan; Saito, Yasuhiko

    2016-10-01

    To assess variation in gender gap (female-male) in inactive life expectancy (IALE) and active life expectancy (ALE) by definition of inactivity. Inactivity, among older Singaporeans, was defined as follows: Scenario 1-health-related difficulty in activities of daily living (ADLs); Scenario 2-health-related difficulty in ADLs/instrumental ADLs (IADLs); Scenario 3-health-related difficulty in ADLs/IADLs or non-health-related non-performance of IADLs. Multistate life tables computed IALE and ALE at age 60, testing three hypotheses: In all scenarios, life expectancy, absolute and relative IALE, and absolute ALE are higher for females (Hypothesis 1 [H1]); gender gap in absolute and relative IALE expands, and in absolute ALE, it contracts in Scenario 2 versus 1 (Hypothesis 2 [H2]); gender gap in absolute and relative IALE decreases, and in absolute ALE, it increases in Scenario 3 versus 2 (Hypothesis 3 [H3]). H1 was supported in Scenarios 1 and 3 but not Scenario 2. Both H2 and H3 were supported. Definition of inactivity influences gender gap in IALE and ALE. © The Author(s) 2016.

  6. Conformal radiotherapy: a glossary

    International Nuclear Information System (INIS)

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

    1999-01-01

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

  7. Conformal scalar field wormholes

    Science.gov (United States)

    Halliwell, Jonathan J.; Laflamme, Raymond

    1989-01-01

    The Euclidian Einstein equations with a cosmological constant and a conformally coupled scalar field are solved, taking the metric to be of the Robertson-Walker type. In the case Lambda = 0, solutions are found which represent a wormhole connecting two asymptotically flat Euclidian regions. In the case Lambda greater than 0, the solutions represent tunneling from a small Tolman-like universe to a large Robertson-Walker universe.

  8. Conformational processing of oncogenic v-Src kinase by the molecular chaperone Hsp90

    Science.gov (United States)

    Boczek, Edgar E.; Reefschläger, Lasse G.; Dehling, Marco; Struller, Tobias J.; Häusler, Elisabeth; Seidl, Andreas; Kaila, Ville R. I.; Buchner, Johannes

    2015-01-01

    Hsp90 is a molecular chaperone involved in the activation of numerous client proteins, including many kinases. The most stringent kinase client is the oncogenic kinase v-Src. To elucidate how Hsp90 chaperones kinases, we reconstituted v-Src kinase chaperoning in vitro and show that its activation is ATP-dependent, with the cochaperone Cdc37 increasing the efficiency. Consistent with in vivo results, we find that Hsp90 does not influence the almost identical c-Src kinase. To explain these findings, we designed Src kinase chimeras that gradually transform c-Src into v-Src and show that their Hsp90 dependence correlates with compactness and folding cooperativity. Molecular dynamics simulations and hydrogen/deuterium exchange of Hsp90-dependent Src kinase variants further reveal increased transitions between inactive and active states and exposure of specific kinase regions. Thus, Hsp90 shifts an ensemble of conformations of v-Src toward high activity states that would otherwise be metastable and poorly populated. PMID:26056257

  9. Conformal geometry computational algorithms and engineering applications

    CERN Document Server

    Jin, Miao; He, Ying; Wang, Yalin

    2018-01-01

    This book offers an essential overview of computational conformal geometry applied to fundamental problems in specific engineering fields. It introduces readers to conformal geometry theory and discusses implementation issues from an engineering perspective.  The respective chapters explore fundamental problems in specific fields of application, and detail how computational conformal geometric methods can be used to solve them in a theoretically elegant and computationally efficient way. The fields covered include computer graphics, computer vision, geometric modeling, medical imaging, and wireless sensor networks. Each chapter concludes with a summary of the material covered and suggestions for further reading, and numerous illustrations and computational algorithms complement the text.  The book draws on courses given by the authors at the University of Louisiana at Lafayette, the State University of New York at Stony Brook, and Tsinghua University, and will be of interest to senior undergraduates, gradua...

  10. Do Running and Strength Exercises Reduce Daily Muscle Inactivity Time?

    Directory of Open Access Journals (Sweden)

    Taija Finni

    2016-09-01

    Full Text Available Understanding how a specific exercise changes daily activity patterns is important when designing physical activity interventions. We examined the effects of strength and interval running exercise sessions on daily activity patterns using recordings of quadriceps and hamstring muscle electromyographic (EMG activity and inactivity. Five male and five female subjects taking part in a 10-week training programme containing both strength and interval running training sessions were measured for daily muscle EMG activities during three days: on a strength day, an interval running day, and a day without exercise. EMG was measured using textile electrodes embedded into sport shorts that were worn 9.1 ± 1.4 hours/day and results are given as % of recording time. During the total measurement time the muscles were inactive 55 ± 26%, 53 ± 30% and 71 ± 12% during strength training day, interval running day, and day without exercise (n.s.. When compared to the day without exercise, the change in muscle inactivity correlated negatively with change in light muscle activity in strength (r = -0.971,p< 0.001 and interval running days (r = -0.965,p< 0.001. While interval running exercise bout induced a more systematic decrease in muscle inactivity time (from 62 ± 15% to 6 ± 6%,p< 0.001, reductions in muscle inactivity in response to strength exercise were highly individual (range 5–70 pp despite the same training programme. Strength, but not running exercise bout, increased muscle activity levels occurring above 50% MVC (p< 0.05 when compared to a similar period without exercise. The effect of strength exercise bout on totaldaily recording time increased the EMG amplitudes across the entire intensity spectrum. While strength and interval running exercise are effective in increasing muscle moderate-to-vigorous activity when compared to a similar period without exercise, it comprises only a small part of the day and does not seem to have a systematic effect

  11. The nucleotide exchange factor Ric-8A is a chaperone for the conformationally dynamic nucleotide-free state of Gαi1.

    Directory of Open Access Journals (Sweden)

    Celestine J Thomas

    Full Text Available Heterotrimeric G protein α subunits are activated upon exchange of GDP for GTP at the nucleotide binding site of Gα, catalyzed by guanine nucleotide exchange factors (GEFs. In addition to transmembrane G protein-coupled receptors (GPCRs, which act on G protein heterotrimers, members of the family cytosolic proteins typified by mammalian Ric-8A are GEFs for Gi/q/12/13-class Gα subunits. Ric-8A binds to Gα•GDP, resulting in the release of GDP. The Ric-8A complex with nucleotide-free Gαi1 is stable, but dissociates upon binding of GTP to Gαi1. To gain insight into the mechanism of Ric-8A-catalyzed GDP release from Gαi1, experiments were conducted to characterize the physical state of nucleotide-free Gαi1 (hereafter referred to as Gαi1[ ] in solution, both as a monomeric species, and in the complex with Ric-8A. We found that Ric-8A-bound, nucleotide-free Gαi1 is more accessible to trypsinolysis than Gαi1•GDP, but less so than Gαi1[ ] alone. The TROSY-HSQC spectrum of [(15N]Gαi1[ ] bound to Ric-8A shows considerable loss of peak intensity relative to that of [(15N]Gαi1•GDP. Hydrogen-deuterium exchange in Gαi1[ ] bound to Ric-8A is 1.5-fold more extensive than in Gαi1•GDP. Differential scanning calorimetry shows that both Ric-8A and Gαi1•GDP undergo cooperative, irreversible unfolding transitions at 47° and 52°, respectively, while nucleotide-free Gαi1 shows a broad, weak transition near 35°. The unfolding transition for Ric-8A:Gαi1[ ] is complex, with a broad transition that peaks at 50°, suggesting that both Ric-8A and Gαi1[ ] are stabilized within the complex, relative to their respective free states. The C-terminus of Gαi1 is shown to be a critical binding element for Ric-8A, as is also the case for GPCRs, suggesting that the two types of GEF might promote nucleotide exchange by similar mechanisms, by acting as chaperones for the unstable and dynamic nucleotide-free state of Gα.

  12. Emerging health problems among women: Inactivity, obesity, and metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Yi-Ju Tsai

    2014-02-01

    Full Text Available The increase in obesity and metabolic syndrome has been documented worldwide. However, few studies have investigated the risk of inactivity, obesity, and metabolic syndrome specifically in women. Hormone balance plays a crucial role in regulating metabolism and helps to maintain optimal health. It is likely that the sex difference in obesity may be due to the variation in hormone concentration throughout a woman's life, which predisposes them to weight gain. This paper reviews previous literature and discusses factors that influence the risk of adiposity-related health consequences among women for three critical biological transitions throughout a woman's life: puberty, menopause, and pregnancy. To improve quality of life and metabolic health for women, interventions are needed to target women at different transition stages and provide tailored health education programs. Interventions should raise awareness of physical inactivity, obesity, and metabolic syndrome, and promote healthy behavioral change in women.

  13. Performance Evaluation of INACT - INDECT Advanced Image Cataloguing Tool

    Directory of Open Access Journals (Sweden)

    Libor Michalek

    2012-01-01

    Full Text Available In this article, we describe the performance evaluation of INACT tool which is developed for cataloguing of high-level and low-level metadata of the evidence material. INACT tool can be used by police forces in the cases of prosecution of such crimes as as possession and distribution of child pornography (CP. In live forensic cases, the time to first hit (time when the first image containing e.g. CP is found is important, as then further legal actions are justified (such as arrest of the suspect and his hardware. The performance evaluation of first hit was performed on real data with the cooperation of Czech Police, Department of Internet Crime.

  14. Investigation of the organic matter in inactive nuclear tank liquids

    International Nuclear Information System (INIS)

    Schenley, R.L.; Griest, W.H.

    1990-08-01

    Environmental Protection Agency (EPA) methodology for regulatory organics fails to account for the organic matter that is suggested by total organic carbon (TOC) analysis in the Oak Ridge National Laboratory (ORNL) inactive nuclear waste-tank liquids and sludges. Identification and measurement of the total organics are needed to select appropriate waste treatment technologies. An initial investigation was made of the nature of the organics in several waste-tank liquids. This report details the analysis of ORNL wastes

  15. 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)

  16. The pulsed migration of hydrocarbons across inactive faults

    Directory of Open Access Journals (Sweden)

    S. D. Harris

    1999-01-01

    Full Text Available Geological fault zones are usually assumed to influence hydrocarbon migration either as high permeability zones which allow enhanced along- or across-fault flow or as barriers to the flow. An additional important migration process inducing along- or across-fault migration can be associated with dynamic pressure gradients. Such pressure gradients can be created by earthquake activity and are suggested here to allow migration along or across inactive faults which 'feel' the quake-related pressure changes; i.e. the migration barriers can be removed on inactive faults when activity takes place on an adjacent fault. In other words, a seal is viewed as a temporary retardation barrier which leaks when a fault related fluid pressure event enhances the buoyancy force and allows the entry pressure to be exceeded. This is in contrast to the usual model where a seal leaks because an increase in hydrocarbon column height raises the buoyancy force above the entry pressure of the fault rock. Under the new model hydrocarbons may migrate across the inactive fault zone for some time period during the earthquake cycle. Numerical models of this process are presented to demonstrate the impact of this mechanism and its role in filling traps bounded by sealed faults.

  17. A profissão de músico conforme apresentada em jornais paraibanos The profession of musician in the paraíba state newspapers

    Directory of Open Access Journals (Sweden)

    Sandra Souza

    2010-04-01

    Full Text Available O artigo relata estudo sobre a profissão dos músicos na Paraíba, realizado por meio da aplicação da análise de conteúdo de dois jornais diários do Estado. A referida análise foi desenvolvida com uma amostra de números referentes aos anos de 2001 e 2003. Identificaram-se quatro categorias (papel social da música; incentivo à música; profissão e organização político-associativas. Tal estudo empírico resultou na identificação de aspectos centrais e importantes na construção da identidade profissional, como: o profissionalismo versus amadorismo; o mito da fama versus o anonimato; desvalorização da chamada prata da casa versus valorização do estrangeiro, etc. Embora não esgotem o tema, situam o lugar que a profissão ocupa na sociedade e pode se constituir em fonte para a elaboração de novas questões e hipóteses para os pesquisadores que se interessarem pela temática.The article reports study on the profession of musicians in the State of Paraíba, conducted by applying the analysis of contents of two daily newspapers of the State. The analysis itself was developed with a sample of issues of the years 2001 and 2003. Four categories were identified (social role of the music; encouraging the music; profession and associative political organization. Such empirical study resulted in the identification of key and important aspects, in the construction of a professional identity, as, professionalism versus amateurism; the myth of fame versus the anonymity; the depreciation of the so-called home talent versus the value of the foreign ones, and so on. Even though this type of media does not exhaust the subject, it establishes the position that the profession occupies in the society and may constitute itself a source for the development of new questions and hypotheses for the researchers interested in the topic.

  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. Classical extended conformal symmetries

    International Nuclear Information System (INIS)

    Viswanathan, R.

    1990-02-01

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

  20. 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...... of flavors. Surprisingly this number, if computed to the order g^2, agrees with previous predictions for the lower boundary of the conformal window for nonsupersymmetric gauge theories. The higher order results tend to predict a higher number of critical flavors. These are universal properties, i...

  1. Physical inactivity affects skeletal muscle insulin signaling in a birth weight-dependent manner

    DEFF Research Database (Denmark)

    Mortensen, Brynjulf; Friedrichsen, Martin; Andersen, Nicoline Resen

    2014-01-01

    We investigated whether physical inactivity could unmask defects in insulin and AMPK signaling in low birth weight (LBW) subjects.......We investigated whether physical inactivity could unmask defects in insulin and AMPK signaling in low birth weight (LBW) subjects....

  2. Louisiana SIP: LAC 33:III Ch. 14 Subchap B, 1431 to 1434--Conformity to State or Federal Implementation Plans of Transportation Plans, Programs, and Projects Developed, Funded, or Approved Under Title 23 U.S.C. or the Federal Transit Laws

    Science.gov (United States)

    Louisiana SIP: LAC 33:III Ch. 14 Subchap B, 1431 to 1434--Conformity to State or Federal Implementation Plans of Transportation Plans, Programs, and Projects Developed, Funded, or Approved Under Title 23 U.S.C. or the Federal Transit Laws

  3. ERICA: leisure-time physical inactivity in Brazilian adolescents

    Science.gov (United States)

    Cureau, Felipe Vogt; da Silva, Thiago Luiz Nogueira; Bloch, Katia Vergetti; Fujimori, Elizabeth; Belfort, Dilson Rodrigues; de Carvalho, Kênia Mara Baiocchi; de Leon, Elisa Brosina; de Vasconcellos, Mauricio Teixeira Leite; Ekelund, Ulf; Schaan, Beatriz D

    2016-01-01

    ABSTRACT OBJECTIVE To evaluate the prevalence of leisure-time physical inactivity in Brazilian adolescents and their association with geographical and sociodemographic variables. METHODS The sample was composed by 74,589 adolescents participating in the Study of Cardiovascular Risks in Adolescents (ERICA). This cross-sectional study of school basis with national scope involved adolescents aged from 12 to 17 years in Brazilian cities with more than 100 thousand inhabitants. The prevalence of leisure-time physical inactivity was categorized according to the volume of weekly practice (< 300; 0 min). The prevalences were estimated for the total sample and by sex. Poisson regression models were used to assess associated factors. RESULTS The prevalence of leisure-time physical inactivity was 54.3% (95%CI 53.4-55.2), and higher for the female sex (70.7%, 95%CI 69.5-71.9) compared to the male (38.0%, 95%CI 36.7-39.4). More than a quarter of adolescents (26.5%, 95%CI 25.8-27.3) reported not practicing physical activity in the leisure time, a condition more prevalent for girls (39.8%, 95%CI 38.8-40.9) than boys (13.4%, 95%CI 12.4-14.4). For girls, the variables that were associated with physical inactivity were: reside in the Northeast (RP = 1.13, 95%CI 1.08-1.19), Southeast (RP = 1.16, 95%CI 1.11-1.22) and South (RP = 1.12, 95%CI 1.06-1.18); have 16-17 years (RP = 1.06, 95%CI 1.12-1.15); and belong to the lower economic class (RP = 1.33, 95%CI 1.20-1.48). The same factors, except reside in the Southeast and South, were also associated with not practicing physical activity in the leisure time for the same group. In males, as well as the region, being older (p < 0.001) and declaring to be indigenous (RP = 0.37, 95%CI 0.19-0.73) were also associated with not practicing physical activities in the leisure time. CONCLUSIONS The prevalence of leisure-time physical inactivity in Brazilian adolescents is high. It presents regional variations and is associated with age and low

  4. 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

  5. 38 CFR 3.372 - Initial grant following inactivity of tuberculosis.

    Science.gov (United States)

    2010-07-01

    ... inactivity of tuberculosis. 3.372 Section 3.372 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF... Considerations Relative to Specific Diseases § 3.372 Initial grant following inactivity of tuberculosis. When... tuberculosis and there is satisfactory evidence that the condition was active previously but is now inactive...

  6. 76 FR 77150 - Approval and Promulgation of Air Quality Implementation Plans; Virginia; General Conformity...

    Science.gov (United States)

    2011-12-12

    ... Promulgation of Air Quality Implementation Plans; Virginia; General Conformity Requirements for Federal... incorporate revisions to Federal general conformity requirements promulgated in July of 2006 and in April of 2010. EPA is approving this Virginia SIP revision to update its state general conformity requirements...

  7. 15 CFR 758.5 - Conformity of documents and unloading of items.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Conformity of documents and unloading... REGULATIONS EXPORT CLEARANCE REQUIREMENTS § 758.5 Conformity of documents and unloading of items. (a) Purpose... country other than that of the ultimate consignee as stated on the export license. (b) Conformity of...

  8. Phosphorylation by PINK1 releases the UBL domain and initializes the conformational opening of the E3 ubiquitin ligase Parkin.

    Directory of Open Access Journals (Sweden)

    Thomas R Caulfield

    2014-11-01

    Full Text Available Loss-of-function mutations in PINK1 or PARKIN are the most common causes of autosomal recessive Parkinson's disease. Both gene products, the Ser/Thr kinase PINK1 and the E3 Ubiquitin ligase Parkin, functionally cooperate in a mitochondrial quality control pathway. Upon stress, PINK1 activates Parkin and enables its translocation to and ubiquitination of damaged mitochondria to facilitate their clearance from the cell. Though PINK1-dependent phosphorylation of Ser65 is an important initial step, the molecular mechanisms underlying the activation of Parkin's enzymatic functions remain unclear. Using molecular modeling, we generated a complete structural model of human Parkin at all atom resolution. At steady state, the Ub ligase is maintained inactive in a closed, auto-inhibited conformation that results from intra-molecular interactions. Evidently, Parkin has to undergo major structural rearrangements in order to unleash its catalytic activity. As a spark, we have modeled PINK1-dependent Ser65 phosphorylation in silico and provide the first molecular dynamics simulation of Parkin conformations along a sequential unfolding pathway that could release its intertwined domains and enable its catalytic activity. We combined free (unbiased molecular dynamics simulation, Monte Carlo algorithms, and minimal-biasing methods with cell-based high content imaging and biochemical assays. Phosphorylation of Ser65 results in widening of a newly defined cleft and dissociation of the regulatory N-terminal UBL domain. This motion propagates through further opening conformations that allow binding of an Ub-loaded E2 co-enzyme. Subsequent spatial reorientation of the catalytic centers of both enzymes might facilitate the transfer of the Ub moiety to charge Parkin. Our structure-function study provides the basis to elucidate regulatory mechanisms and activity of the neuroprotective Parkin. This may open up new avenues for the development of small molecule Parkin

  9. Deletion of DXZ4 on the human inactive X chromosome alters higher-order genome architecture

    Science.gov (United States)

    Darrow, Emily M.; Huntley, Miriam H.; Dudchenko, Olga; Stamenova, Elena K.; Durand, Neva C.; Sun, Zhuo; Huang, Su-Chen; Sanborn, Adrian L.; Machol, Ido; Shamim, Muhammad; Seberg, Andrew P.; Lander, Eric S.; Chadwick, Brian P.; Aiden, Erez Lieberman

    2016-01-01

    During interphase, the inactive X chromosome (Xi) is largely transcriptionally silent and adopts an unusual 3D configuration known as the “Barr body.” Despite the importance of X chromosome inactivation, little is known about this 3D conformation. We recently showed that in humans the Xi chromosome exhibits three structural features, two of which are not shared by other chromosomes. First, like the chromosomes of many species, Xi forms compartments. Second, Xi is partitioned into two huge intervals, called “superdomains,” such that pairs of loci in the same superdomain tend to colocalize. The boundary between the superdomains lies near DXZ4, a macrosatellite repeat whose Xi allele extensively binds the protein CCCTC-binding factor. Third, Xi exhibits extremely large loops, up to 77 megabases long, called “superloops.” DXZ4 lies at the anchor of several superloops. Here, we combine 3D mapping, microscopy, and genome editing to study the structure of Xi, focusing on the role of DXZ4. We show that superloops and superdomains are conserved across eutherian mammals. By analyzing ligation events involving three or more loci, we demonstrate that DXZ4 and other superloop anchors tend to colocate simultaneously. Finally, we show that deleting DXZ4 on Xi leads to the disappearance of superdomains and superloops, changes in compartmentalization patterns, and changes in the distribution of chromatin marks. Thus, DXZ4 is essential for proper Xi packaging. PMID:27432957

  10. Dimensional reduction for conformal blocks

    Science.gov (United States)

    Hogervorst, Matthijs

    2016-09-01

    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 3 d conformal blocks as an infinite sum over 2 F 1 hypergeometric functions with closed-form coefficients.

  11. The structure of DLP12 endolysin exhibiting alternate loop conformation and comparative analysis with other endolysins.

    Science.gov (United States)

    Babu, Kesavan; Arulandu, Arockiasamy; Sankaran, Krishnaswamy

    2017-11-27

    The lytic enzyme, endolysin, is encoded by bacteriophages (phages) to destroy the peptidoglycan layer of host bacterial cells. The release of phage progenies to start the new infection cycle is dependent on the cell lysis event. Endolysin encoded by DLP12 cryptic prophage is a SAR endolysin which is retained by the bacterium presumably due to the benefit it confers. The structure of DLP12 endolysin (Id: 4ZPU) determined at 2.4 Å resolution is presented here. The DLP12 endolysin structure shows a modular nature and is organized into distinct structural regions. One of the monomers has the loops at the active site in a different conformation. This has led to a suggestion of depicting possibly active and inactive state of DLP12 endolysin. Comparison of DLP12 endolysin structure and sequence with those of related endolysins shows the core three-dimensional fold is similar and the catalytic triad geometry is highly conserved despite the sequence differences. Features essential for T4 lysozyme structure and function such as the distance between catalytic groups, salt bridge and presence of nucleophilic water are conserved in DLP12 endolysin and other endolysins analyzed. © 2017 Wiley Periodicals, Inc.

  12. Metaphase chromosome analysis by ligation-mediated PCR: heritable chromatin structure and a comparison of active and inactive X chromosomes.

    OpenAIRE

    Hershkovitz, M; Riggs, A D

    1995-01-01

    We report that ligation-mediated PCR (LMPCR) can be used for high-resolution study of metaphase chromosomes, and we discuss the role of metaphase chromatin structure in the preservation of differentiated cell states. The X chromosome-linked human PGK1 (phosphoglycerate kinase 1) promoter region was investigated, and euchromatic active X chromosome (Xa) metaphase chromatin was compared with interphase Xa chromatin and to heterochromatic inactive X chromosome (Xi) metaphase and interphase chrom...

  13. Metabolic rates and biochemical compositions of Apostichopus japonicus (Selenka) tissue during periods of inactivity

    Science.gov (United States)

    Bao, Jie; Dong, Shuanglin; Tian, Xiangli; Wang, Fang; Gao, Qinfeng; Dong, Yunwei

    2010-03-01

    Estivation, hibernation, and starvation are indispensable inactive states of sea cucumbers Apostichopus japonicus in nature and in culture ponds. Generally, temperature is the principal factor that induces estivation or hibernation in the sea cucumber. The present study provided insight into the physiological adaptations of A. japonicus during the three types of inactivity (hibernation, estivation, and starvation) by measuring the oxygen consumption rates ( Vo2) and biochemical compositions under laboratory conditions of low (3°C), normal (17°C) and high (24°C) temperature. The results show that the characteristics of A. japonicus in dormancy (hibernation and estivation) states were quite different from higher animals, such as fishes, amphibians, reptiles, and mammals, but more closely resembled a semi-dormant state. It was observed that the shift in the A. japonicus physiological state from normal to dormancy was a chronic rather than acute process, indicated by the gradual depression of metabolic rate. While metabolic rates declined 44.9% for the estivation group and 71.7% for the hibernation group, relative to initial rates, during the 36 d culture period, metabolic rates were not maintained at constant levels during these states. The metabolic depression processes for sea cucumbers in hibernation and estivation appeared to be a passive and an active metabolic suppression, respectively. In contrast, the metabolic rates (128.90±11.70 μg/g h) of estivating sea cucumbers were notably higher (107.85±6.31 μg/g h) than in starving sea cucumbers at 17°C, which indicated that the dormancy mechanism here, as a physiological inhibition, was not as efficient as in higher animals. Finally, the principle metabolic substrate or energy source of sea cucumbers in hibernation was lipid, whereas in estivation they mainly consumed protein in the early times and both protein and lipid thereafter.

  14. Structures of human Bruton's tyrosine kinase in active and inactive conformations suggest a mechanism of activation for TEC family kinases.

    Science.gov (United States)

    Marcotte, Douglas J; Liu, Yu-Ting; Arduini, Robert M; Hession, Catherine A; Miatkowski, Konrad; Wildes, Craig P; Cullen, Patrick F; Hong, Victor; Hopkins, Brian T; Mertsching, Elisabeth; Jenkins, Tracy J; Romanowski, Michael J; Baker, Darren P; Silvian, Laura F

    2010-03-01

    Bruton's tyrosine kinase (BTK), a member of the TEC family of kinases, plays a crucial role in B-cell maturation and mast cell activation. Although the structures of the unphosphorylated mouse BTK kinase domain and the unphosphorylated and phosphorylated kinase domains of human ITK are known, understanding the kinase selectivity profiles of BTK inhibitors has been hampered by the lack of availability of a high resolution, ligand-bound BTK structure. Here, we report the crystal structures of the human BTK kinase domain bound to either Dasatinib (BMS-354825) at 1.9 A resolution or to 4-amino-5-(4-phenoxyphenyl)-7H-pyrrolospyrimidin- 7-yl-cyclopentane at 1.6 A resolution. This data provides information relevant to the development of small molecule inhibitors targeting BTK and the TEC family of nonreceptor tyrosine kinases. Analysis of the structural differences between the TEC and Src families of kinases near the Trp-Glu-Ile motif in the N-terminal region of the kinase domain suggests a mechanism of regulation of the TEC family members.

  15. Reflections on Conformal Spectra

    CERN Multimedia

    CERN. Geneva

    2015-01-01

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

  16. Instantons in conformal gravity

    International Nuclear Information System (INIS)

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

    1984-01-01

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

  17. DNA methylation profiles of human active and inactive X chromosomes.

    Science.gov (United States)

    Sharp, Andrew J; Stathaki, Elisavet; Migliavacca, Eugenia; Brahmachary, Manisha; Montgomery, Stephen B; Dupre, Yann; Antonarakis, Stylianos E

    2011-10-01

    X-chromosome inactivation (XCI) is a dosage compensation mechanism that silences the majority of genes on one X chromosome in each female cell. To characterize epigenetic changes that accompany this process, we measured DNA methylation levels in 45,X patients carrying a single active X chromosome (X(a)), and in normal females, who carry one X(a) and one inactive X (X(i)). Methylated DNA was immunoprecipitated and hybridized to high-density oligonucleotide arrays covering the X chromosome, generating epigenetic profiles of active and inactive X chromosomes. We observed that XCI is accompanied by changes in DNA methylation specifically at CpG islands (CGIs). While the majority of CGIs show increased methylation levels on the X(i), XCI actually results in significant reductions in methylation at 7% of CGIs. Both intra- and inter-genic CGIs undergo epigenetic modification, with the biggest increase in methylation occurring at the promoters of genes silenced by XCI. In contrast, genes escaping XCI generally have low levels of promoter methylation, while genes that show inter-individual variation in silencing show intermediate increases in methylation. Thus, promoter methylation and susceptibility to XCI are correlated. We also observed a global correlation between CGI methylation and the evolutionary age of X-chromosome strata, and that genes escaping XCI show increased methylation within gene bodies. We used our epigenetic map to predict 26 novel genes escaping XCI, and searched for parent-of-origin-specific methylation differences, but found no evidence to support imprinting on the human X chromosome. Our study provides a detailed analysis of the epigenetic profile of active and inactive X chromosomes.

  18. On Associative Conformal Algebras of Linear Growth

    OpenAIRE

    Retakh, Alexander

    2000-01-01

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

  19. 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.

  20. Cold-active alkaline phosphatase is irreversibly transformed into an inactive dimer by low urea concentrations.

    Science.gov (United States)

    Hjörleifsson, Jens Guðmundur; Ásgeirsson, Bjarni

    2016-07-01

    Alkaline phosphatase is a homodimeric metallo-hydrolase where both Zn(2+) and Mg(2+) are important for catalysis and stability. Cold-adapted alkaline phosphatase variants have high activity at low temperatures and lower thermal stability compared with variants from mesophilic hosts. The instability, and thus inactivation, could be due to loose association of the dimers and/or loosely bound Mg(2)(+) in the active site, but this has not been studied in detail for the cold-adapted variants. Here, we focus on using the intrinsic fluorescence of Trp in alkaline phosphatase from the marine bacterium Vibrio splendidus (VAP) to probe for dimerization. Trp→Phe substitutions showed that two out of the five native Trp residues contributed mostly to the fluorescence emission. One residue, 15Å away from the active site (W460) and highly solvent excluded, was phosphorescent and had a distant role in substrate binding. An additional Trp residue was introduced to the dimer interface to act as a possible probe for dimerization. Urea denaturation curves indicated that an inactive dimer intermediate, structurally equivalent to the native state, was formed before dimer dissociation took place. This is the first example of the transition of a native dimer to an inactive dimer intermediate for alkaline phosphatase without using mutagenesis, ligands, or competitive inhibition. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Classical Virasoro irregular conformal block

    Science.gov (United States)

    Rim, Chaiho; Zhang, Hong

    2015-07-01

    Virasoro irregular conformal block with arbitrary rank is obtained for the classical limit or equivalently Nekrasov-Shatashvili limit using the beta-deformed irregular matrix model (Penner-type matrix model for the irregular conformal block). The same result is derived using the generalized Mathieu equation which is equivalent to the loop equation of the irregular matrix model.

  2. Classical Virasoro irregular conformal block

    Energy Technology Data Exchange (ETDEWEB)

    Rim, Chaiho; Zhang, Hong [Department of Physics and Center for Quantum Spacetime (CQUeST), Sogang University,Seoul 121-742 (Korea, Republic of)

    2015-07-30

    Virasoro irregular conformal block with arbitrary rank is obtained for the classical limit or equivalently Nekrasov-Shatashvili limit using the beta-deformed irregular matrix model (Penner-type matrix model for the irregular conformal block). The same result is derived using the generalized Mathieu equation which is equivalent to the loop equation of the irregular matrix model.

  3. 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.

  4. Conformal gravity and time

    Science.gov (United States)

    Hazboun, Jeffrey Shafiq

    2014-10-01

    Cartan geometry provides a rich formalism from which to look at various geometrically motivated extensions to general relativity. In this manuscript, we start by motivating reasons to extend the theory of general relativity. We then introduce the reader to our technique, called the quotient manifold method, for extending the geometry of spacetime. We will specifically look at the class of theories formed from the various quotients of the conformal group. Starting with the conformal symmetries of Euclidean space, we construct a manifold where time manifests as a part of the geometry. Though there is no matter present in the geome- try studied here, geometric terms analogous to dark energy and dark matter appear when we write down the Einstein tensor. Specifically, the quotient of the conformal group of Euclidean four-space by its Weyl subgroup results in a geometry possessing many of the properties of relativistic phase space, including both a natural symplectic form and nondegenerate Killing metric. We show the general solution possesses orthogonal Lagrangian submanifolds, with the induced metric and the spin connection on the submanifolds necessarily Lorentzian, despite the Euclidean starting point. By examining the structure equations of the biconformal space in an orthonormal frame adapted to its phase space properties, we also find two new tensor fields exist in this geometry, not present in Riemannian geometry. The first is a combination of the Weyl vector with the scale factor on the metric, and determines the time-like directions on the submanifolds. The second comes from the components of the spin connection, symmetric with respect to the new metric. Though this field comes from the spin connection, it transforms ho- mogeneously. Finally, we show in the absence of Cartan curvature or sources, the configuration space has geometric terms equivalent to a perfect fluid and a cosmological constant. We complete the analysis of this homogeneous space by

  5. ERICA: leisure-time physical inactivity in Brazilian adolescents.

    Science.gov (United States)

    Cureau, Felipe Vogt; da Silva, Thiago Luiz Nogueira; Bloch, Katia Vergetti; Fujimori, Elizabeth; Belfort, Dilson Rodrigues; de Carvalho, Kênia Mara Baiocchi; de Leon, Elisa Brosina; de Vasconcellos, Mauricio Teixeira Leite; Ekelund, Ulf; Schaan, Beatriz D

    2016-02-01

    OBJECTIVE To evaluate the prevalence of leisure-time physical inactivity in Brazilian adolescents and their association with geographical and sociodemographic variables. METHODS The sample was composed by 74,589 adolescents participating in the Study of Cardiovascular Risks in Adolescents (ERICA). This cross-sectional study of school basis with national scope involved adolescents aged from 12 to 17 years in Brazilian cities with more than 100 thousand inhabitants. The prevalence of leisure-time physical inactivity was categorized according to the volume of weekly practice (Southeast (RP = 1.16, 95%CI 1.11-1.22) and South (RP = 1.12, 95%CI 1.06-1.18); have 16-17 years (RP = 1.06, 95%CI 1.12-1.15); and belong to the lower economic class (RP = 1.33, 95%CI 1.20-1.48). The same factors, except reside in the Southeast and South, were also associated with not practicing physical activity in the leisure time for the same group. In males, as well as the region, being older (p Brazilian adolescents is high. It presents regional variations and is associated with age and low socioeconomic status. Special attention should be given to girls and to those who do not engage in any physical activity during the leisure time, so that they can adopt a more active lifestyle.

  6. 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.

  7. Projectors, shadows, and conformal blocks

    Energy Technology Data Exchange (ETDEWEB)

    Simmons-Duffin, David [Jefferson Physical Laboratory, Harvard University,Cambridge, MA 02138 (United States)

    2014-04-24

    We introduce a method for computing conformal blocks of operators in arbitrary Lorentz representations in any spacetime dimension, making it possible to apply bootstrap techniques to operators with spin. The key idea is to implement the “shadow formalism' of Ferrara, Gatto, Grillo, and Parisi in a setting where conformal invariance is manifest. Conformal blocks in d-dimensions can be expressed as integrals over the projective null-cone in the “embedding space' ℝ{sup d+1,1}. Taking care with their analytic structure, these integrals can be evaluated in great generality, reducing the computation of conformal blocks to a bookkeeping exercise. To facilitate calculations in four-dimensional CFTs, we introduce techniques for writing down conformally-invariant correlators using auxiliary twistor variables, and demonstrate their use in some simple examples.

  8. Structural alphabets derived from attractors in conformational space

    Directory of Open Access Journals (Sweden)

    Kleinjung Jens

    2010-02-01

    Full Text Available Abstract Background The hierarchical and partially redundant nature of protein structures justifies the definition of frequently occurring conformations of short fragments as 'states'. Collections of selected representatives for these states define Structural Alphabets, describing the most typical local conformations within protein structures. These alphabets form a bridge between the string-oriented methods of sequence analysis and the coordinate-oriented methods of protein structure analysis. Results A Structural Alphabet has been derived by clustering all four-residue fragments of a high-resolution subset of the protein data bank and extracting the high-density states as representative conformational states. Each fragment is uniquely defined by a set of three independent angles corresponding to its degrees of freedom, capturing in simple and intuitive terms the properties of the conformational space. The fragments of the Structural Alphabet are equivalent to the conformational attractors and therefore yield a most informative encoding of proteins. Proteins can be reconstructed within the experimental uncertainty in structure determination and ensembles of structures can be encoded with accuracy and robustness. Conclusions The density-based Structural Alphabet provides a novel tool to describe local conformations and it is specifically suitable for application in studies of protein dynamics.

  9. Impact of poor sleep quality and physical inactivity on cognitive function in community-dwelling older adults.

    Science.gov (United States)

    Nakakubo, Sho; Makizako, Hyuma; Doi, Takehiko; Tsutsumimoto, Kota; Lee, Sangyoon; Lee, Sungchul; Hotta, Ryo; Bae, Seongryu; Suzuki, Takao; Shimada, Hiroyuki

    2017-11-01

    The purpose of the present study was to examine whether the combination of subjective sleep quality and physical activity is associated with cognitive performance among community-dwelling older adults. Cross-sectional data on 5381 older adults who participated in part of the National Center for Geriatrics and Gerontology - Study of Geriatric Syndromes were analyzed. We assessed general cognitive impairment using the Mini-Mental State Examination, and also assessed story memory, attention, executive function and processing speed using the National Center for Geriatrics and Gerontology Functional Assessment Tool. Physical activity was assessed using two questionnaires, and participants were categorized as active or inactive. Sleep quality was assessed using the Pittsburgh Sleep Quality Index, and participants were categorized as having poor (PS) or good sleep quality (GS). Participants in the inactive + PS group had worse performances than those in the active + GS group in all cognitive measures (Mini-Mental State Examination: P = 0.008, story memory: P = 0.007, other cognitive measures: P sleep quality were associated with poor cognitive performance among community-dwelling older adults. The combination of poor sleep quality and physical inactivity also worsened cognitive performance. Geriatr Gerontol Int 2017; 17: 1823-1828. © 2017 Japan Geriatrics Society.

  10. Intensity modulated conformal radiotherapy

    International Nuclear Information System (INIS)

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

    2006-12-01

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

  11. On conformal invariance in gauge theories. Quantum electrodynamics

    International Nuclear Information System (INIS)

    Zaikov, R.P.

    1983-01-01

    In the present paper another nontrivial model of the conformal quantum electrodynamics is proposed. The main hypothesis is that the electromagnetic potential together with an additional zero scale, dimensional scalar field is transformed by a nonbasic and, consequently, nondecomposable representation of the conformal group. There are found nontrivial conformal covariant two-point functions and an invariant action from which equations of motion are derived. There is considered the covariant procedure of quantization and it is shown that the norm of one-particle physical states is positive definite

  12. Regulation of dCTP deaminase from Escherichia coli by nonallosteric dTTP binding to an inactive form of the enzyme

    DEFF Research Database (Denmark)

    Johansson, Eva; Thymark, Majbritt; Bynck, Julie H

    2007-01-01

    -maximal activity and the cooperativity of dCTP saturation. Likewise, increasing concentrations of dCTP increase the cooperativity of dTTP inhibition. Previous structural studies showed that the complexes of inactive mutant protein, E138A, with dUTP or dCTP bound, and wild-type enzyme with dUTP bound were all...... highly similar and characterized by having an ordered C-terminal. When comparing with a new structure in which dTTP is bound to the active site of E138A, the region between Val120 and His125 was found to be in a new conformation. This and the previous conformation were mutually exclusive within...

  13. Benchmarking Commercial Conformer Ensemble Generators.

    Science.gov (United States)

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

    2017-11-27

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

  14. Conformal Lorentz geometry revisited

    Science.gov (United States)

    Teleman, Kostake

    1996-02-01

    The group U(2,2) and its subgroup SU(2,2) were considered by Penrose in his study of the conformal compactification M of the Minkowski space M [R. Penrose and W. Rindler, Spinors and Space-Time (Cambridge University, Cambridge, 1986) and R. O. Wells, Jr., Bull. Am. Math. Soc. I, 2 (1979)]. The standard representation of SU(2,2) in C4 and in M are the corner stones of twistor theory, which was created by Penrose to the double purpose of obtaining new solutions of Einstein equations and new insights on gravitational radiation. We think that other representations of SU(2,2) or U(2,2) could also bring some information in relativity [see also, Barut O. Asjim, in Noncompact Lie Groups and some of their Applications, edited by E. A. Tanner and R. Wilson (Kluwer Academic, Dordrecht, 1994), p. 103] and, accordingly, we propose an extension of Penrose twistor program. In this paper we deal with a new U(2,2)-space, which we denote by W. We show first that the SU(2,2)-space M introduced by Penrose is isomorphic to U(2), endowed with an action of SU(2,2) given by non-Abelian homographic transformations. These transformations keep invariant the equation det(u-v)=0, characterizing the pairs (u,v)∈U(2)×U(2) such that ``u lies on the light-cone of v.'' By definition, our space W consists of all pairs (u,v)∈U(2)×U(2) satisfying the condition det(u-v)≠0. The starting point of this article is the observation that W carries an SU(2,2)-invariant pseudo-Riemannian metric L:=Tr[(u-v)-1u˙ ×(u-v)-1v˙], of signature (4,4). (W,L) is in fact an irreducible symmetric space in Cartan's sense, which is isomorphic to the quotient SO(2,4)/S[O(1,1)×O(1,3)]. As an irreducible symmetric space, it is an 8-dimensional Einstein space, whose Ricci tensor is proportional to the metric tensor. We study the geodesic paths of this space giving the general solutions in terms of initial data and studying the constants of motion. In particular we determine the geodesic paths which exhibit two periods

  15. Harmony of spinning conformal blocks

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-03-15

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

  16. Harmony of spinning conformal blocks

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-12-07

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

  17. Projectors, Shadows, and Conformal Blocks

    OpenAIRE

    Simmons-Duffin, David

    2012-01-01

    We introduce a method for computing conformal blocks of operators in arbitrary Lorentz representations in any spacetime dimension, making it possible to apply bootstrap techniques to operators with spin. The key idea is to implement the “shadow formalism” of Ferrara, Gatto, Grillo, and Parisi in a setting where conformal invariance is manifest. Conformal blocks in d -dimensions can be expressed as integrals over the projective null-cone in the “embedding space” $ \\mathbb{R} $ d +1,1 . Taking ...

  18. Guidelines for cleanup of uranium tailings from inactive mills

    International Nuclear Information System (INIS)

    Goldsmith, W.A.; Haywood, F.F.; Jacobs, D.G.

    1975-01-01

    Recent experiences in Grand Junction, Colorado, have indicated the significance of uranium tailings as sources of nonoccupational exposure and suggest that current methods for perpetual care and isolation of the large areas covered by tailings piles at inactive mill locations may be inadequate for minimizing human exposure. This paper presents the rationale and the procedures used in reviewing the adequacy of proposed criteria for remedial action at these sites. Exposures due to aquatic, terrestrial, airborne, and direct contamination pathways were compared to determine the most important radionuclides in the pile and their pathways to man. It is shown that the most hazardous components of the tailings are 226 Ra and 230 Th. The long half-lives of these radionuclides require the consideration of continuous occupancy of the vacated site at some future time, even if the immediately projected land use does not anticipate maximum exposure

  19. Program for closure of an inactive radioactive waste disposal site at the Savannah River Plant

    International Nuclear Information System (INIS)

    Cook, J.R.

    1987-01-01

    The 643-G Radioactive Waste Disposal Facility was operated at the Savannah River Plant from 1952 through 1974, and has been inactive since that time. The actions leading to closure of 643-G will involve a combination of activities consisting of limited waste removal, stabilization, capping, and monitoring. The overall effect of these closure actions will be to place the 643-G site in a physically and chemically stable state which will remain stable over a long period of time. During a one-hundred year institutional control period surveillance and monitoring of the site will be carried out to verify that the performance of the system is acceptable, and access of the general public to the site will be restricted. The program described in this paper is a recommendation; the actual closure plan will be negotiated with regulatory authorities. 2 figs., 1 tab

  20. Remedial Action Plan and final design for stabilization of the inactive uranium mill tailings at Green River, Utah

    International Nuclear Information System (INIS)

    Matthews, M.L.; Alkema, K.

    1991-03-01

    This Remedial Action Plan (RAP) has been developed to serve a threefold purpose. It presents the series of activities that are proposed by the US Department of Energy (DOE) to accomplish long-term stabilization and control of radioactive materials at the inactive uranium processing site located near Green River, Utah. It provides a characterization of the present conditions of the site. It also serves to document the concurrence of the state of Utah and the US Nuclear Regulatory Commission (NRC) in the remedial action. This agreement, upon execution by the DOE and the state of Utah, and concurrence by the NRC, becomes Appendix 8 of the Cooperative Agreement

  1. Loop Electrostatics Asymmetry Modulates the Preexisting Conformational Equilibrium in Thrombin.

    Science.gov (United States)

    Pozzi, Nicola; Zerbetto, Mirco; Acquasaliente, Laura; Tescari, Simone; Frezzato, Diego; Polimeno, Antonino; Gohara, David W; Di Cera, Enrico; De Filippis, Vincenzo

    2016-07-19

    Thrombin exists as an ensemble of active (E) and inactive (E*) conformations that differ in their accessibility to the active site. Here we show that redistribution of the E*-E equilibrium can be achieved by perturbing the electrostatic properties of the enzyme. Removal of the negative charge of the catalytic Asp102 or Asp189 in the primary specificity site destabilizes the E form and causes a shift in the 215-217 segment that compromises substrate entrance. Solution studies and existing structures of D102N document stabilization of the E* form. A new high-resolution structure of D189A also reveals the mutant in the collapsed E* form. These findings establish a new paradigm for the control of the E*-E equilibrium in the trypsin fold.

  2. [Physical inactivity in Galicia (Spain): trends and the impact of changes in the definition].

    Science.gov (United States)

    Pérez-Ríos, Mónica; Santiago-Pérez, María I; Rodríguez-Camacho, Elena; Malvar, Alberto; Suanzes, Jorge; Hervada, Xurxo

    2015-01-01

    To estimate the prevalence of physical inactivity during leisure time in Galicia (Spain) between 2007 and 2011 and to assess the impact of including non-leisure time activities in the definition of physical inactivity. A cross-sectional study was conducted in the population aged 16 years and older (n=19,235). Physical activity was assessed by the Minnesota Questionnaire. In 2011, inactivity was estimated by including daily activities. Between 2007 and 2011, the prevalence of inactivity in Galicia remained stable (p=0.249) and close to 50%. This prevalence was higher among women and those who worked or were in education. Inactivity decreased from 47% to 16% when non-leisure time activities were included in the definition. Between 2007 and 2011 in Galicia, the prevalence of inactivity remained high and stable. This prevalence was significantly decreased when non-leisure time activities were included in the definition. Copyright © 2014 SESPAS. Published by Elsevier Espana. All rights reserved.

  3. Calculating a checksum with inactive networking components in a computing system

    Science.gov (United States)

    Aho, Michael E; Chen, Dong; Eisley, Noel A; Gooding, Thomas M; Heidelberger, Philip; Tauferner, Andrew T

    2014-12-16

    Calculating a checksum utilizing inactive networking components in a computing system, including: identifying, by a checksum distribution manager, an inactive networking component, wherein the inactive networking component includes a checksum calculation engine for computing a checksum; sending, to the inactive networking component by the checksum distribution manager, metadata describing a block of data to be transmitted by an active networking component; calculating, by the inactive networking component, a checksum for the block of data; transmitting, to the checksum distribution manager from the inactive networking component, the checksum for the block of data; and sending, by the active networking component, a data communications message that includes the block of data and the checksum for the block of data.

  4. Higher-derivative generalization of conformal mechanics

    Science.gov (United States)

    Baranovsky, Oleg

    2017-08-01

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

  5. Radial Coordinates for Conformal Blocks

    CERN Document Server

    Hogervorst, Matthijs

    2013-01-01

    We develop the theory of conformal blocks in CFT_d expressing them as power series with Gegenbauer polynomial coefficients. Such series have a clear physical meaning when the conformal block is analyzed in radial quantization: individual terms describe contributions of descendants of a given spin. Convergence of these series can be optimized by a judicious choice of the radial quantization origin. We argue that the best choice is to insert the operators symmetrically. We analyze in detail the resulting "rho-series" and show that it converges much more rapidly than for the commonly used variable z. We discuss how these conformal block representations can be used in the conformal bootstrap. In particular, we use them to derive analytically some bootstrap bounds whose existence was previously found numerically.

  6. 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.

  7. 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...

  8. Inverse bootstrapping conformal field theories

    Science.gov (United States)

    Li, Wenliang

    2018-01-01

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

  9. Aspect of the conformal invariance

    International Nuclear Information System (INIS)

    Bauer, M.

    1990-11-01

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

  10. Naturality in conformal field theory

    International Nuclear Information System (INIS)

    Moore, G.; Seiberg, N.

    1989-01-01

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

  11. Linking Geology and Microbiology: Inactive Pockmarks Affect Sediment Microbial Community Structure

    OpenAIRE

    Haverkamp, Thomas H. A.; Hammer, Øyvind; Jakobsen, Kjetill S.

    2014-01-01

    Pockmarks are geological features that are found on the bottom of lakes and oceans all over the globe. Some are active, seeping oil or methane, while others are inactive. Active pockmarks are well studied since they harbor specialized microbial communities that proliferate on the seeping compounds. Such communities are not found in inactive pockmarks. Interestingly, inactive pockmarks are known to have different macrofaunal communities compared to the surrounding sediments. It is undetermined...

  12. Distal histidine conformational flexibility in dehaloperoxidase from Amphitrite ornata.

    Science.gov (United States)

    Chen, Zuxu; de Serrano, Vesna; Betts, Laurie; Franzen, Stefan

    2009-01-01

    The enzyme dehaloperoxidase (DHP) from the terebellid polychaete Amphitrite ornata is a heme protein which has a globin fold but can function as both a hemoglobin and a peroxidase. As a peroxidase, DHP is capable of converting 2,4,6-trihalophenols to the corresponding 2,6-dihaloquinones in the presence of hydrogen peroxide. As a hemoglobin, DHP cycles between the oxy and deoxy states as it reversibly binds oxygen for storage. Here, it is reported that the distal histidine, His55, exhibits conformational flexibility in the deoxy form and is consequently observed in two solvent-exposed conformations more than 9.5 A away from the heme. These conformations are analogous to the open conformation of sperm whale myoglobin. The heme iron in deoxy ferrous DHP is five-coordinate and has an out-of-plane displacement of 0.25 A from the heme plane. The observation of five-coordinate heme iron with His55 in a remote solvent-exposed conformation is consistent with the hypothesis that His55 interacts with heme iron ligands through hydrogen bonding in the closed conformation. Since His55 is also displaced by the binding of 4-iodophenol in an internal pocket, these results provide new insight into the correlation between heme iron ligation, molecular binding in the distal pocket and the conformation of the distal histidine in DHP.

  13. Distal histidine conformational flexibility in dehaloperoxidase from Amphitrite ornata

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Zuxu; de Serrano, Vesna; Betts, Laurie; Franzen, Stefan; (NCSU); (UNC)

    2009-01-28

    The enzyme dehaloperoxidase (DHP) from the terebellid polychaete Amphitrite ornata is a heme protein which has a globin fold but can function as both a hemoglobin and a peroxidase. As a peroxidase, DHP is capable of converting 2,4,6-trihalophenols to the corresponding 2,6-dihaloquinones in the presence of hydrogen peroxide. As a hemoglobin, DHP cycles between the oxy and deoxy states as it reversibly binds oxygen for storage. Here, it is reported that the distal histidine, His55, exhibits conformational flexibility in the deoxy form and is consequently observed in two solvent-exposed conformations more than 9.5 {angstrom} away from the heme. These conformations are analogous to the open conformation of sperm whale myoglobin. The heme iron in deoxy ferrous DHP is five-coordinate and has an out-of-plane displacement of 0.25 {angstrom} from the heme plane. The observation of five-coordinate heme iron with His55 in a remote solvent-exposed conformation is consistent with the hypothesis that His55 interacts with heme iron ligands through hydrogen bonding in the closed conformation. Since His55 is also displaced by the binding of 4-iodophenol in an internal pocket, these results provide new insight into the correlation between heme iron ligation, molecular binding in the distal pocket and the conformation of the distal histidine in DHP.

  14. Food withdrawal lowers energy expenditure and induces inactivity in long-chain fatty acid oxidation-deficient mouse models.

    Science.gov (United States)

    Diekman, Eugene F; van Weeghel, Michel; Wanders, Ronald J A; Visser, Gepke; Houten, Sander M

    2014-07-01

    Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is an inherited disorder of mitochondrial long-chain fatty acid β-oxidation (FAO). Patients with VLCAD deficiency may present with hypoglycemia, hepatomegaly, cardiomyopathy, and myopathy. Although several mouse models have been developed to aid in the study of the pathogenesis of long-chain FAO defects, the muscular phenotype is underexposed. To address the muscular phenotype, we used a newly developed mouse model on a mixed genetic background with a more severe defect in FAO (LCAD(-/-); VLCAD(+/-)) in addition to a validated mouse model (LCAD(-/-); VLCAD(+/+)) and compared them with wild-type (WT) mice. We found that both mouse models show a 20% reduction in energy expenditure (EE) and a 3-fold decrease in locomotor activity in the unfed state. In addition, we found a 1.7°C drop in body temperature in unfed LCAD(-/-); VLCAD(+/+) mice compared with WT body temperature. We conclude that food withdrawal-induced inactivity, hypothermia, and reduction in EE are novel phenotypes associated with FAO deficiency in mice. Unexpectedly, inactivity was not explained by rhabdomyolysis, but rather reflected the overall reduced capacity of these mice to generate heat. We suggest that mice are partly protected against the negative consequence of an FAO defect.-Diekman, E. F., van Weeghel, M., Wanders, R. J. A., Visser, G., Houten, S. M. Food withdrawal lowers energy expenditure and induces inactivity in long-chain fatty acid oxidation-deficient mouse models. © FASEB.

  15. New open conformation of SMYD3 implicates conformational selection and allostery

    Energy Technology Data Exchange (ETDEWEB)

    Spellmon, Nicholas; Sun, Xiaonan; Xue, Wen; Holcomb, Joshua; Chakravarthy, Srinivas; Shang, Weifeng; Edwards, Brian; Sirinupong, Nualpun; Li, Chunying; Yang, Zhe (GSU); (Wayne State U-MED); (IIT); (Songkla)

    2016-01-01

    SMYD3 plays a key role in cancer cell viability, adhesion, migration and invasion. SMYD3 promotes formation of inducible regulatory T cells and is involved in reducing autoimmunity. However, the nearly “closed” substrate-binding site and poor in vitro H3K4 methyltransferase activity have obscured further understanding of this oncogenically related protein. Here we reveal that SMYD3 can adopt an “open” conformation using molecular dynamics simulation and small-angle X-ray scattering. This ligand-binding-capable open state is related to the crystal structure-like closed state by a striking clamshell-like inter-lobe dynamics. The two states are characterized by many distinct structural and dynamical differences and the conformational transition pathway is mediated by a reversible twisting motion of the C-terminal domain (CTD). The spontaneous transition from the closed to open states suggests two possible, mutually non-exclusive models for SMYD3 functional regulation and the conformational selection mechanism and allostery may regulate the catalytic or ligand binding competence of SMYD3. This study provides an immediate clue to the puzzling role of SMYD3 in epigenetic gene regulation.

  16. Association between Natural Resources for OutdoorActivities and Physical Inactivity

    Data.gov (United States)

    U.S. Environmental Protection Agency — it includes available natural resources for outdoor activities, Physical inactivity and households income. This dataset is associated with the following publication:...

  17. THE EVOLUTION OF SOME BIOCHEMICAL PARAMETERS IN THE HONEYBEES’ HAEMOLYMPH (A. M. CARPATHICA COLLECTED IN THE INACTIVE SEASON

    Directory of Open Access Journals (Sweden)

    AGRIPINA SAPCALIU

    2008-10-01

    Full Text Available The biochemical analyses of the blood are largely used for the routine diagnosis and especially for the metabolic survey in farm animals. These facts conduct us to the idea that similar analyses, applied on honeybee hemolymph, could be used IN monitoring the healthy state of honeybee colonies. The present studies represent preliminary researches, which aimed to investigate the variability of the main biochemical parameters in the hemolymph of the healthy honeybees (Apis mellifera in inactive season. The researches were carried out on honeybee samples collected from 5 honeybee colonies belonging to a breeding apiary of the Institute for Beekeeping Research and Development from Bucharest. In order to perform the biochemical analyses, the honeybees samples, consisting in 50 individuals on sample (10 individuals/colony were randomly collected and their haemolimph collected, at different time intervals, in inactive season (fall-winter. Totally, there were collected 250 haemolyph samples in a 2 years interval and the following 21 biochemical parameters were analysed: GLU, HDL-c, ALP, T-cho, Tprot, Alb., BUN, LDH, CPK,, Mg, IP, GGT, GOT, GPT, Ca, Cre,, Amy, T–BIL, TG, UA.. The test was carried out after the collection and processing of the samples using the SPOTCHEM EZSP4430, equipment with dry kits, the slides technique, respectively .During the 2nd part of the inactive season, the values of most biochemical parameters increase in different proportions, their levels being maintained also in the first part of the active seasons (April, May, June.The values obtained for the main studied biochemical parameters in the haemolymph of the healthy honeybees collected from honeybee colonies kept in natural conditions show a highly variable evolution in the two consecutive years of experiments during the inactive season.

  18. Agonist induction, conformational selection, and mutant receptors.

    Science.gov (United States)

    Giraldo, Jesús

    2004-01-02

    Current models of receptor activation are based on either of two basic mechanisms: agonist induction or conformational selection. The importance of one pathway relative to the other is controversial. In this article, the impossibility of distinguishing between the two mechanisms under a thermodynamic approach is shown. The effect of receptor mutation on the constants governing ligand-receptor equilibria is discussed. The two-state model of agonism both in its original formulation (one cycle) and including multiple active states (multiple cycles) is used. Pharmacological equations for the double (two cycles) two-state model are derived. The simulations performed suggest that the double two-state model of agonism can be a useful model for assessing quantitatively the changes in pharmacological activity following receptor mutation.

  19. Entanglement entropy from the truncated conformal space

    Directory of Open Access Journals (Sweden)

    T. Palmai

    2016-08-01

    Full Text Available A new numerical approach to entanglement entropies of the Rényi type is proposed for one-dimensional quantum field theories. The method extends the truncated conformal spectrum approach and we will demonstrate that it is especially suited to study the crossover from massless to massive behavior when the subsystem size is comparable to the correlation length. We apply it to different deformations of massless free fermions, corresponding to the scaling limit of the Ising model in transverse and longitudinal fields. For massive free fermions the exactly known crossover function is reproduced already in very small system sizes. The new method treats ground states and excited states on the same footing, and the applicability for excited states is illustrated by reproducing Rényi entropies of low-lying states in the transverse field Ising model.

  20. 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.

  1. 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.

  2. Quantum Conformal Algebras and Closed Conformal Field Theory

    CERN Document Server

    Anselmi, D

    1999-01-01

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

  3. Conformal anomaly of generalized form factors and finite loop integrals

    CERN Document Server

    Chicherin, Dmitry

    2017-01-01

    We reveal a new mechanism of conformal symmetry breaking at Born level. It occurs in generalized form factors with several local operators and an on-shell state of massless particles. The effect is due to hidden singularities on collinear configurations of the momenta. This conformal anomaly is different from the holomorphic anomaly of amplitudes. We present a number of examples in four and six dimensions. We find an application of the new conformal anomaly to finite loop momentum integrals with one or more massless legs. The collinear region around a massless leg creates a contact anomaly, made visible by the loop integration. The anomalous conformal Ward identity for an $\\ell-$loop integral is a 2nd-order differential equation whose right-hand side is an $(\\ell-1)-$loop integral. We show several examples, in particular the four-dimensional scalar double box.

  4. Burden of physical inactivity and hospitalization costs due to chronic diseases

    Science.gov (United States)

    Bielemann, Renata Moraes; da Silva, Bruna Gonçalves Cordeiro; Coll, Carolina de Vargas Nunes; Xavier, Mariana Otero; da Silva, Shana Ginar

    2015-01-01

    OBJECTIVE To evaluate the physical inactivity-related inpatient costs of chronic non-communicable diseases. METHODS This study used data from 2013, from Brazilian Unified Health System, regarding inpatient numbers and costs due to malignant colon and breast neoplasms, cerebrovascular diseases, ischemic heart diseases, hypertension, diabetes, and osteoporosis. In order to calculate the share physical inactivity represents in that, the physical inactivity-related risks, which apply to each disease, were considered, and physical inactivity prevalence during leisure activities was obtained from Pesquisa Nacional por Amostra de Domicílio (Brazil’s National Household Sample Survey). The analysis was stratified by genders and residing country regions of subjects who were 40 years or older. The physical inactivity-related hospitalization cost regarding each cause was multiplied by the respective share it regarded to. RESULTS In 2013, 974,641 patients were admitted due to seven different causes in Brazil, which represented a high cost. South region was found to have the highest patient admission rate in most studied causes. The highest prevalences for physical inactivity were observed in North and Northeast regions. The highest inactivity-related share in men was found for osteoporosis in all regions (≈ 35.0%), whereas diabetes was found to have a higher share regarding inactivity in women (33.0% to 37.0% variation in the regions). Ischemic heart diseases accounted for the highest total costs that could be linked to physical inactivity in all regions and for both genders, being followed by cerebrovascular diseases. Approximately 15.0% of inpatient costs from Brazilian Unified Health System were connected to physical inactivity. CONCLUSIONS Physical inactivity significantly impacts the number of patient admissions due to the evaluated causes and through their resulting costs, with different genders and country regions representing different shares. PMID:26487291

  5. Burden of physical inactivity and hospitalization costs due to chronic diseases

    Directory of Open Access Journals (Sweden)

    Renata Moraes Bielemann

    2015-01-01

    Full Text Available OBJECTIVE To evaluate the physical inactivity-related inpatient costs of chronic non-communicable diseases.METHODS This study used data from 2013, from Brazilian Unified Health System, regarding inpatient numbers and costs due to malignant colon and breast neoplasms, cerebrovascular diseases, ischemic heart diseases, hypertension, diabetes, and osteoporosis. In order to calculate the share physical inactivity represents in that, the physical inactivity-related risks, which apply to each disease, were considered, and physical inactivity prevalence during leisure activities was obtained from Pesquisa Nacional por Amostra de Domicílio(Brazil's National Household Sample Survey. The analysis was stratified by genders and residing country regions of subjects who were 40 years or older. The physical inactivity-related hospitalization cost regarding each cause was multiplied by the respective share it regarded to.RESULTS In 2013, 974,641 patients were admitted due to seven different causes in Brazil, which represented a high cost. South region was found to have the highest patient admission rate in most studied causes. The highest prevalences for physical inactivity were observed in North and Northeast regions. The highest inactivity-related share in men was found for osteoporosis in all regions (≈ 35.0%, whereas diabetes was found to have a higher share regarding inactivity in women (33.0% to 37.0% variation in the regions. Ischemic heart diseases accounted for the highest total costs that could be linked to physical inactivity in all regions and for both genders, being followed by cerebrovascular diseases. Approximately 15.0% of inpatient costs from Brazilian Unified Health System were connected to physical inactivity.CONCLUSIONS Physical inactivity significantly impacts the number of patient admissions due to the evaluated causes and through their resulting costs, with different genders and country regions representing different shares.

  6. Circumnuclear Dust in Nearby Active and Inactive Galaxies. I. Data

    Science.gov (United States)

    Martini, Paul; Regan, Michael W.; Mulchaey, John S.; Pogge, Richard W.

    2003-06-01

    The detailed morphology of the interstellar medium (ISM) in the central kiloparsec of galaxies is controlled by pressure and gravitation. The combination of these forces shapes both circumnuclear star formation and the growth of the central, supermassive black hole. We present visible and near-infrared Hubble Space Telescope images and color maps of 123 nearby galaxies that show the distribution of the cold ISM, as traced by dust, with excellent spatial resolution. These observations reveal that nuclear dust spirals are found in the majority of active and inactive galaxies and they possess a wide range in coherence, symmetry, and pitch angle. We have used this large sample to develop a classification system for circumnuclear dust structures. In spite of the heterogeneous nature of the complete sample, we only find symmetric, two-arm nuclear dust spirals in galaxies with large-scale bars, and these dust lanes clearly connect to dust lanes along the leading edges of the large-scale bars. Not all dust lanes along large-scale bars form two-arm spirals, however, and several instead end in nuclear rings. We find that tightly wound, or low pitch angle, nuclear dust spirals are more common in unbarred galaxies than barred galaxies. Finally, the extended narrow-line region in several of the active galaxies is well resolved. The connection between the ionized gas and circumnuclear dust lanes in four of these galaxies provides additional evidence that a significant fraction of their extended narrow-line region is ambient gas photoionized in situ by the active nucleus. In a future paper we will use our classification system for circumnuclear dust to identify differences between active and inactive galaxies, as well as barred and unbarred galaxies, in well-matched subsamples of these data. Based on observations with the NASA/ESA Hubble Space Telescope obtained at the Space Telescope Science Institute, which is operated by the Association of Universities for Research in

  7. Conformation of hindered piperidines: Spectroscopic evidence for ...

    Indian Academy of Sciences (India)

    Administrator

    The preferred conformations of both the isomeric forms of nitrosamines were determined by comparison of ... found to possess pharmacological activity and form an essential part of the molecular structure of important drugs. 1 ... chair conformation. The relative preference among the various conformers in the conformational ...

  8. Radioactive spheres without inactive wall for lesion simulation in PET

    International Nuclear Information System (INIS)

    Bazanez-Borgert, M.; Bundschuh, R.A.; Herz, M.; Martinez, M.J.; Schwaiger, M.; Ziegler, S.I.

    2008-01-01

    With the growing importance of PET and PET/CT in diagnosis, staging, therapy monitoring and radiotherapy planning, appropriate tools to simulate lesions in phantoms are important. Normally hollow spheres, made of plastic or glass, which can be filled with radioactive solutions, are used. As these spheres have an inactive wall they do not reflect the real situation in the patient and lead to quantification errors in the presence of background activity. We propose spheres made of radioactive wax, which are easy to produce, give a high flexibility to the user and a more accurate quantification. These wax spheres were evaluated for their applicability in PET phantoms and it was found that the activity is not diffusing into the surrounding water in relevant quantities, that they show a sufficient homogeneity, and that their attenuation properties are equivalent to water for photons of PET energies. Recovery coefficients for the wax spheres were measured and compared with those obtained for fillable plastic spheres for diameters of 28, 16, 10, and 6 mm in the presence of background activity. Recovery coefficients of the wax spheres were found to be up to 21% higher than for the fillable spheres. (orig.)

  9. Physical Activity, Inactivity and Health During Youth-2016.

    Science.gov (United States)

    Rowlands, Alex V

    2017-02-01

    2016 has been an exciting year for research in physical activity, inactivity and health. Recognition of the importance of all physical behaviors (physical activity, sedentary time and sleep) across the 24-hr day continues to grow. Notable advances have included: applications of recent methodological innovations that account for the codependence of the behaviors in the finite 24-hr period showing that the balance of these behaviors is associated with health; methodological innovations focusing on the classification of behaviors and/or quantification of the 24-hr diurnal activity pattern; and a series of systematic reviews that helped provide the evidence base for the release of the innovative 24-hr movement guidelines earlier this year. This commentary focuses on just two of these papers: the first by Goldsmith and colleagues who demonstrate a new statistical method that exploits the time series nature of accelerometer data facilitating new insights into time-specific determinants of children's activity patterns and associations with health; the second by Tremblay and colleagues who describe the evidence base for associations between each physical behavior and children's health, the emerging evidence base for associations between the balance of behaviors and health, and development of the world's first 24-hr movement guidelines.

  10. Physical inactivity, neurological disability, and cardiorespiratory fitness in multiple sclerosis.

    Science.gov (United States)

    Motl, R W; Goldman, M

    2011-02-01

    We examined the associations among physical activity, neurological disability, and cardiorespiratory fitness in two studies of individuals with multiple sclerosis (MS). Study 1 included 25 women with relapsing-remitting MS (RRMS) who undertook an incremental exercise test for measuring peak oxygen (VO₂(peak) ) consumption, wore an accelerometer during a 7-day period, and completed the Godin Leisure-Time Exercise Questionnaire (GLTEQ). Study 2 was a follow-up of Study 1 and included 24 women with RRMS who completed the self-reported Expanded Disability Status Scale (EDSS), undertook an incremental exercise test, wore an accelerometer during a 7-day period, and completed the GLTEQ. Study 1 indicated that VO₂(peak) was significantly correlated with accelerometer counts (pr = 0.69) and GLTEQ scores (pr = 0.63) even after controlling for age and MS duration. Study 2 indicated that VO₂(peak) was significantly correlated with accelerometer counts (pr = 0.50), GLTEQ scores (pr = 0.59), and EDSS scores (pr = -0.43) even after controlling for age and MS duration; there was a moderate partial correlation between accelerometer counts and EDSS scores (pr = -0.43). Multiple linear regression analysis indicated that both accelerometer counts (β = 0.32) and EDSS scores (β = -0.40) had statistically significant associations with VO₂(peak). The findings indicate that physical inactivity and neurological disability might represent independent risk factors for reduced levels of cardiorespiratory fitness in this population. © 2010 John Wiley & Sons A/S.

  11. Home Delivery Medicament Program: access, inactivity and cardiovascular risk.

    Science.gov (United States)

    Araújo, Roque da Silva; Arcuri, Edna Apparecida Moura; Lopes, Victor Cauê

    2016-10-10

    to verify causes of inactivity in the Home Delivery Medicament Program, as referred by users from a Primary Health Care Service in São Paulo, comparing them to the causes registered in the program and analyzing them in the theoretical model Concept of Access to Health. cross-sectional study, interviewing 111 inactive users; and documentary study in the program records. half of the users did not know the condition of inactivity. Discrepancies were found between the user's and the program's information, observing different levels of agreement: Absence of physician and administrative staff member 0%; Transfer to other service 25%; Death 50%; Option to quit 50%; Address change 57% and Change in therapeutic schedule 80%. The users' feeling of accepting the program was observed. In the health access concept, inactivity can be explained in the information dimension, in the degree of asymmetry between the patient's and the health professional's knowledge, identified through the indicators: education, knowledge and information sources. due to the low education level, the user does not assimilate the information on the steps of the program flowchart, does not return for the assessment that guarantees its continuity. Consequently, (s)he stops receiving the medication and spends a long time without treatment, increasing the cardiovascular risk of hypertensive (92% of the sample), diabetic (44%) and dyslipidemic patients (31%). verificar causas de inatividade no Programa Remédio em Casa, referidas por usuários de Unidade Básica de Saúde de São Paulo, comparando-as às registradas pelo programa e analisando-as no modelo teórico Conceito de Acesso à Saúde. estudo transversal entrevistando 111 usuários inativos; e documental, nos registros do programa. metade dos usuários desconhecia a condição de inatividade. Constatadas discrepâncias nas informações usuário versus programa, observando-se diferentes níveis de concordância: Falta de médico e funcion

  12. Is the Canadian childhood obesity epidemic related to physical inactivity?

    Science.gov (United States)

    Tremblay, M S; Willms, J D

    2003-09-01

    This study examined the relation among children's physical activity, sedentary behaviours, and body mass index (BMI), while controlling for sex, family structure, and socioeconomic status. Epidemiological study examining the relations among physical activity participation, sedentary behaviour (video game use and television (TV)/video watching), and BMI on a nationally representative sample of Canadian children. A representative sample of Canadian children aged 7-11 (N=7216) from the 1994 National Longitudinal Survey of Children and Youth was used in the analysis. Physical activity and sport participation, sedentary behaviour (video game use and TV/video watching), and BMI measured by parental report. Both organized and unorganized sport and physical activity are negatively associated with being overweight (10-24% reduced risk) or obese (23-43% reduced risk), while TV watching and video game use are risk factors for being overweight (17-44% increased risk) or obese (10-61% increased risk). Physical activity and sedentary behaviour partially account for the association of high socioeconomic status and two-parent family structure with the likelihood of being overweight or obese. This study provides evidence supporting the link between physical inactivity and obesity of Canadian children.

  13. Protein conformational exchange measured by {sup 1}H R{sub 1{rho}} relaxation dispersion of methyl groups

    Energy Technology Data Exchange (ETDEWEB)

    Weininger, Ulrich [Lund University, Department of Biophysical Chemistry, Center for Molecular Protein Science (Sweden); Blissing, Annica T.; Hennig, Janosch; Ahlner, Alexandra [Linkoeping University, Division of Molecular Biotechnology, Department of Physics, Chemistry and Biology (Sweden); Liu, Zhihong; Vogel, Hans J. [University of Calgary, Department of Biological Sciences, Biochemistry Research Group (Canada); Akke, Mikael, E-mail: mikael.akke@bpc.liu.se [Lund University, Department of Biophysical Chemistry, Center for Molecular Protein Science (Sweden); Lundstroem, Patrik, E-mail: patlu@ifm.liu.se [Linkoeping University, Division of Molecular Biotechnology, Department of Physics, Chemistry and Biology (Sweden)

    2013-09-15

    Activated dynamics plays a central role in protein function, where transitions between distinct conformations often underlie the switching between active and inactive states. The characteristic time scales of these transitions typically fall in the microsecond to millisecond range, which is amenable to investigations by NMR relaxation dispersion experiments. Processes at the faster end of this range are more challenging to study, because higher RF field strengths are required to achieve refocusing of the exchanging magnetization. Here we describe a rotating-frame relaxation dispersion experiment for {sup 1}H spins in methyl {sup 13}CHD{sub 2} groups, which improves the characterization of fast exchange processes. The influence of {sup 1}H-{sup 1}H rotating-frame nuclear Overhauser effects (ROE) is shown to be negligible, based on a comparison of R{sub 1{rho}} relaxation data acquired with tilt angles of 90 Degree-Sign and 35 Degree-Sign , in which the ROE is maximal and minimal, respectively, and on samples containing different {sup 1}H densities surrounding the monitored methyl groups. The method was applied to ubiquitin and the apo form of calmodulin. We find that ubiquitin does not exhibit any {sup 1}H relaxation dispersion of its methyl groups at 10 or 25 Degree-Sign C. By contrast, calmodulin shows significant conformational exchange of the methionine methyl groups in its C-terminal domain, as previously demonstrated by {sup 1}H and {sup 13}C CPMG experiments. The present R{sub 1{rho}} experiment extends the relaxation dispersion profile towards higher refocusing frequencies, which improves the definition of the exchange correlation time, compared to previous results.

  14. Associations of unhealthy lifestyle factors with sexual inactivity and sexual dysfunctions in Denmark

    DEFF Research Database (Denmark)

    Christensen, Birgitte S; Grønbaek, Morten; Pedersen, Bo V

    2011-01-01

    Studies have linked obesity, a sedentary lifestyle, and tobacco smoking to erectile dysfunction, but the evidence linking unhealthy lifestyle factors to other sexual dysfunctions or to sexual inactivity is conflicting.......Studies have linked obesity, a sedentary lifestyle, and tobacco smoking to erectile dysfunction, but the evidence linking unhealthy lifestyle factors to other sexual dysfunctions or to sexual inactivity is conflicting....

  15. Time course of arterial vascular adaptations to inactivity and paralyses in humans.

    NARCIS (Netherlands)

    Groot, P.C.E. de; Kuppevelt, D. van; Pons, C.; Snoek, G.V.E.; Woude, L.H.V. van der; Hopman, M.T.E.

    2003-01-01

    PURPOSE: The aim of the present study was to assess the time course of vascular adaptations to inactivity and paralyses in humans. The spinal cord-injured (SCI) population offers a unique "human model of nature" to assess peripheral vascular adaptations and its time course to extreme inactivity and

  16. Time course of arterial vascular adaptations to inactivity and paralyses in humans

    NARCIS (Netherlands)

    de Groot, P.C.E.; van Kuppevelt, D.; Pons, C.; van der Woude, L.H.V.; Hopman, M.T.E.

    2003-01-01

    Purpose: The aim of the present study was to assess the time course of vascular adaptations to inactivity and paralyses in humans. The spinal cord-injured (SCI) population offers a unique "human model of nature" to assess peripheral vascular adaptations and its time course to extreme inactivity and

  17. Childhood adversities and socioeconomic position as predictors of leisure-time physical inactivity in early adulthood

    NARCIS (Netherlands)

    Kestilä, Laura; Mäki-Opas, Tomi; Kunst, Anton E.; Borodulin, Katja; Rahkonen, Ossi; Prättälä, Ritva

    2015-01-01

    Limited knowledge exists on how childhood social, health-related and economic circumstances predict adult physical inactivity. Our aim was a) to examine how various childhood adversities and living conditions predict leisure-time physical inactivity in early adulthood and b) to find out whether

  18. Physical inactivity, abdominal obesity and risk of coronary heart disease in apparently healthy men and women

    NARCIS (Netherlands)

    Arsenault, B. J.; Rana, J. S.; Lemieux, I.; Després, J.-P.; Kastelein, J. J. P.; Boekholdt, S. M.; Wareham, N. J.; Khaw, K.-T.

    2010-01-01

    Objective: To test the hypothesis that for any given body mass index (BMI) category, active individuals would have a smaller waist circumference than inactive individuals. Our second objective was to examine the respective contribution of waist circumference and physical inactivity on coronary heart

  19. In Search of Lost Springs: A Protocol for Locating Active and Inactive Springs.

    Science.gov (United States)

    Fensham, R J; Silcock, J L; Powell, O; Habermehl, M A

    2016-05-01

    Groundwater springs are significant landscape features for humans and the biota that occupies their habitat. Many springs become inactive where groundwater exploitation by humans has lowered the water table or artesian pressure. In order to assess this impact, it is important to identify and locate active, and with more difficulty, inactive springs. Using a variety of archival, environmental and field-based data, this study presents a protocol for the determination of the location and status of springs across the Great Artesian Basin of Australia. This protocol underpins a database of springs, which is not only important for the assessment of spring ecosystems, but also contributes to understand groundwater extraction impacts and hydrogeological processes. The database indicates that 30.0% of discharge (artesian) springs in the Great Artesian Basin are entirely inactive and another 11.8% are partially inactive. For the outcrop (gravity) springs of the Basin, only 1.9% are entirely inactive and 7.4% partially inactive, and for the outcrop springs in the Tertiary sandstone overlying the Basin 30.9% are inactive and 18.2% are partially inactive. © 2015, National Ground Water Association.

  20. validity and reliability of a physical activity/inactivity questionnaire in ...

    African Journals Online (AJOL)

    of engaging in physical activity, sports or play. 3,12,15,27,39, .... and recorded to the nearest 0.1 mm. Percentage body fat was calculated using standard equations.11. Instruments. Physical activity/inactivity over a period of 7 days was as- sessed using a ..... benefits is required, particularly in children where inactivity and the ...

  1. 37 CFR 11.20 - Disciplinary sanctions; Transfer to disability inactive status.

    Science.gov (United States)

    2010-07-01

    ..., Investigations, and Proceedings § 11.20 Disciplinary sanctions; Transfer to disability inactive status. (a) Types...; Transfer to disability inactive status. 11.20 Section 11.20 Patents, Trademarks, and Copyrights UNITED... discipline exist, may impose on a practitioner the following types of discipline: (1) Exclusion from practice...

  2. Annual status report on the inactive uranium mill tailings sites remedial action program

    Energy Technology Data Exchange (ETDEWEB)

    1979-12-01

    Assessments of inactive uranium mill tailings sites in the United States led to the designation of 25 processing sites for remedial action under the provisions of Section 102(a) Public Law 95-604. The Department of Energy assessed the potential health effects to the public from the residual radioactive materials on or near the 25 sites; and, with the advice of the Environmental Protection Agency, the Secretary established priorities for performing remedial action. In designating the 25 sites and establishing the priorities for performing remedial action, the Department of Energy consulted with the Environmental Protection Agency, Nuclear Regulatory Commission, Department of the Interior, governors of the affected States, Navajo Nation, and appropriate property owners. Public participation in this process was encouraged. During Fiscal Year 1980, Department of Energy will be conducting surveys to verify the radiological characterization at the designated processing sites; developing cooperative agreements with the affected States; and initiating the appropriate National Environmental Policy Act documentation prior to conducting specific remedial actions.

  3. 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.

  4. Conformal geometry and quasiregular mappings

    CERN Document Server

    Vuorinen, Matti

    1988-01-01

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

  5. Relationship between Physical Inactivity and Health Characteristics among Participants in an Employee Wellness Program

    Science.gov (United States)

    Birdee, Gurjeet S.; Byrne, Daniel W.; McGown, Paula W.; Rothman, Russell L.; Rolando, Lori A.; Holmes, Marilyn C.; Yarbrough, Mary I.

    2013-01-01

    Objective To characterize factors associated with physical inactivity among employees with access to workplace wellness program. Methods We examined data on physical inactivity, defined as exercise less than once a week, from the 2010 health risk assessment (HRA) completed by employees at a major academic institution (n=16,976). Results Among employees, 18% individuals reported physical activity less than once a week. Individuals who were physically inactive as compared with physically active reported higher prevalence of cardiovascular diseases (AOR 1.36 [1.23–1.51], fair or poor health status (AOR 3.52 [2.97–4.17]) and absenteeism from work (AOR 1.59 [1.41–1.79]). Overall, physically inactive employees as compared to physically active employees reported more interest in health education programs. Conclusions Future research is needed to address barriers to physical inactivity to improve employee wellness and potentially lower health utility costs. PMID:23618884

  6. Predictors of physical inactivity among elderly malaysians: recommendations for policy planning.

    Science.gov (United States)

    Kaur, Jasvindar; Kaur, Gurpreet; Ho, Bee Kiau; Yao, Weng Keong; Salleh, Mohmad; Lim, Kuang Hock

    2015-04-01

    Physical inactivity is the fourth leading risk factor for global mortality. Regular moderate-intensity physical activity has significant benefits for health. To determine the socioeconomic predictors of physical inactivity among elderly Malaysian population. A nationwide community-based survey was conducted among 4831 respondents aged ≥60 years with a face-to-face questionnaire. The prevalence of physical inactivity among the elderly was 88.0%, highest in respondents aged older than 80 years (95.4%), females (90.1%), other Bumiputra (92.2%), earning household income less than RM1000 (87.9%), and residing in urban locality (88.4%). In the multivariate model, the predictors of physical inactivity were only sex, ethnicity, locality, and age group (adjusted odds ratio = 1.3-3.6). The predictors of physical inactivity can identify the risk factors to develop policies that will reduce the public health burden of noncommunicable diseases. © 2014 APJPH.

  7. Conformational entropic maps of functional coupling domains in GPCR activation: A case study with beta2 adrenergic receptor

    Science.gov (United States)

    Liu, Fan; Abrol, Ravinder; Goddard, William, III; Dougherty, Dennis

    2014-03-01

    Entropic effect in GPCR activation is poorly understood. Based on the recent solved structures, researchers in the GPCR structural biology field have proposed several ``local activating switches'' that consisted of a few number of conserved residues, but have long ignored the collective dynamical effect (conformational entropy) of a domain comprised of an ensemble of residues. A new paradigm has been proposed recently that a GPCR can be viewed as a composition of several functional coupling domains, each of which undergoes order-to-disorder or disorder-to-order transitions upon activation. Here we identified and studied these functional coupling domains by comparing the local entropy changes of each residue between the inactive and active states of the β2 adrenergic receptor from computational simulation. We found that agonist and G-protein binding increases the heterogeneity of the entropy distribution in the receptor. This new activation paradigm and computational entropy analysis scheme provides novel ways to design functionally modified mutant and identify new allosteric sites for GPCRs. The authors thank NIH and Sanofi for funding this project.

  8. 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

  9. SUSY Unparticle and Conformal Sequestering

    Energy Technology Data Exchange (ETDEWEB)

    Nakayama, Yu; Nakayama, Yu

    2007-07-17

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

  10. Geographical Variations in the Environmental Determinants of Physical Inactivity among U.S. Adults.

    Science.gov (United States)

    An, Ruopeng; Li, Xinye; Jiang, Ning

    2017-10-31

    Physical inactivity is a major modifiable risk factor for morbidity, disability and premature mortality worldwide. This study assessed the geographical variations in the impact of environmental quality on physical inactivity among U.S. adults. Data on county-level prevalence of leisure-time physical inactivity came from the Behavioral Risk Factor Surveillance System. County environment was measured by the Environmental Quality Index (EQI), a comprehensive index of environmental conditions that affect human health. The overall EQI consists of five subdomains-air, water, land, social, and built environment. Geographically weighted regressions (GWRs) were performed to estimate and map county-specific impact of overall EQI and its five subdomains on physical inactivity prevalence. The prevalence of leisure-time physical inactivity among U.S. counties was 25% in 2005. On average, one standard deviation decrease in the overall EQI was associated with an increase in county-level prevalence of leisure-time physical inactivity by nearly 1%. However, substantial geographical variations in the estimated environmental determinants of physical inactivity were present. The estimated changes of county-level prevalence of leisure-time physical inactivity resulted from one standard deviation decrease of the overall EQI ranged from an increase of over 3% to a decrease of nearly 2% across U.S. counties. Analogous, the estimated changes of county-level prevalence of leisure-time physical inactivity resulted from one standard deviation decrease of the EQI air, water, land, social, and built environment subdomains ranged from an increase of 2.6%, 1.5%, 2.9%, 3.3%, and 1.7% to a decrease of 2.9%, 1.4%, 2.4%, 2.4%, and 0.8% across U.S. counties, respectively. Given the substantial heterogeneities in the environmental determinants of physical inactivity, locally customized physical activity interventions are warranted to address the most concerning area-specific environmental issue.

  11. 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. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Influence of Crystal Packing on Global Protein Conformation

    Science.gov (United States)

    Ahlstrom, Logan; Miyashita, Osamu

    2011-10-01

    X-ray crystallography is the most robust method for solving protein structure. However, packing forces in the crystal lattice select just a snapshot of a protein's conformational ensemble, whereas proteins are flexible and can adopt different conformations. Here we compare molecular dynamics (MD) simulations in solution and the crystal lattice to add dynamical insight to the static X-ray images of proteins. As a model system, we consider the λ Cro dimer, whose solved X-ray structures range from a ``closed'' to an ``open'' global conformation. Free energy profiles depicting the conformational space sampled by the dimer in solution show some reported structures correspond to stable states. Yet other conformations, while accessible, lie higher in energy, indicating the effect of crystal packing. Subsequent crystal MD simulations estimated the strength of packing interfaces in the lattice, showing the influence of crystal form and mutation in stabilizing different dimer conformations. Our quantitative results will aid analysis of X-ray data in establishing protein structure-function relationships.

  13. Conformational changes in hemoglobin triggered by changing the iron charge

    International Nuclear Information System (INIS)

    Croci, S.; Achterhold, K.; Ortalli, I.; Parak, F. G.

    2008-01-01

    In this work the hemoglobin conformational changes induced by changing the iron charge have been studied and compared with Myoglobin. Moessbauer spectroscopy was used to follow the change of the iron conformation. In order to compare the conformational relaxation of hemoglobin and myoglobin, and to study a possible influence of the quaternary structure, an intermediate metastable state of hemoglobin has been created by low temperature X-ray irradiation of methemoglobin. The irradiation reduces the Fe(III) of the heme groups to Fe(II) Low Spin, where the water is still bound on the sixth coordination. Heating cycles performed at temperatures from 140 K to 200 K allow the molecules to overcome an activation energy barrier and to relax into a stable conformation such as deoxy-hemoglobin or carboxy-hemoglobin, if CO is present. Slightly different structures (conformational substates) reveal themselves as a distribution of energy barriers (ΔG). The distribution of the activation energy, for the decay of the Fe(II) Low Spin intermediate, has been fitted with a Gaussian. For comparison, published myoglobin data were re-analysed in the same way. The average energy value at characteristic temperature is very similar in case of myoglobin and hemoglobin. The larger Gaussian energy distribution for myoglobin with respect to hemoglobin shows that more conformational substates are available. This may be caused by a larger area exposed to water. In hemoglobin, part of the surface of the chains is not water accessible due to the quaternary structure.

  14. Effects of physical activity and inactivity on muscle fatigue

    Directory of Open Access Journals (Sweden)

    Gregory C. Bogdanis

    2012-05-01

    Full Text Available The aim of this review was to examine the mechanisms by which physical activity and inactivity modify muscle fatigue. It is well known that acute or chronic increases in physical activity result in structural, metabolic, hormonal, neural and molecular adaptations that increase the level of force or power that can be sustained by a muscle. These adaptations depend on the type, intensity and volume of the exercise stimulus, but recent studies have highlighted the role of high intensity, short duration exercise as a time-efficient method to achieve both anaerobic and aerobic/endurance type adaptations. The factors that determine the fatigue profile of a muscle during intense exercise include muscle fibre composition, neuromuscular characteristics high energy metabolite stores, buffering capacity, ionic regulation, capillarization and mitochondrial density. Muscle fiber type transformation during exercise training is usually towards the intermediate type IIA at the expense of both type I and type IIx myosin heavy chain isoforms. High intensity training results in increases of both glycolyic and oxidative enzymes, muscle capilarization, improved phosphocreatine resynthesis and regulation of K+, H+ and lactate ions. Decreases of the habitual activity level due to injury or sedentary lifestyle result in partial or even compete reversal of the adaptations due to previous training, manifested by reductions in fibre cross-sectional area, decreased oxidative capacity and capillarization. Complete immobilization due to injury results in markedly decreased force output and fatigue resistance. Muscle unloading reduces electromyographic activity and causes muscle atrophy and significant decreases in capillarization and oxidative enzymes activity. The last part of the review discusses the beneficial effects of intermittent high intensity exercise training in patients with different health conditions to demonstrate the powerful effect exercise on health and well

  15. Motor-Driven (Passive) Cycling: A Potential Physical Inactivity Countermeasure?

    Science.gov (United States)

    Peterman, James E.; Wright, Kenneth P.; Melanson, Edward L.; Kram, Rodger; Byrnes, William C.

    2016-01-01

    We have previously shown that motor-driven (passive) stationary cycling elevates energy expenditure (EE). Purpose To quantify how acute passive cycling affects glucose and insulin responses to an oral glucose tolerance test (OGTT) and basic cognition compared to sitting and moderate-intensity active cycling. Methods Twenty-four physically inactive healthy males completed three trials in randomized order involving 30-minute conditions of sitting, passive cycling and moderate-intensity cycling. During each condition, EE was measured and participants performed cognitive tests. Following each condition, a 2-hour OGTT was performed. Results EE was significantly higher during the cycling conditions compared to sitting (1.36±0.58 and 6.50±1.73 kcal·min−1 greater than sitting for passive and moderate-intensity, respectively). A significant correlation was found between body fat percentage and post-sitting OGTT 2-h post plasma glucose (r2=0.30, pcycling lowered 2-h post plasma glucose (7.7±1.3 vs. 6.9±1.6mmol·L−1, respectively, pcycling had similar beneficial effects on 2-h post plasma glucose and WBISI. Cognitive performance did not significantly differ between the sitting and passive cycling conditions. Conclusion 2-h post plasma glucose was lower and WBISI following acute passive cycling was higher in non-lean participants. Given that and the increase in EE without changes in cognitive performance, we propose passive cycling as a promising intervention to counteract some of the deleterious effects of prolonged sitting in the workplace. PMID:27054677

  16. Effects of Physical Activity and Inactivity on Muscle Fatigue

    Science.gov (United States)

    Bogdanis, Gregory C.

    2012-01-01

    The aim of this review was to examine the mechanisms by which physical activity and inactivity modify muscle fatigue. It is well known that acute or chronic increases in physical activity result in structural, metabolic, hormonal, neural, and molecular adaptations that increase the level of force or power that can be sustained by a muscle. These adaptations depend on the type, intensity, and volume of the exercise stimulus, but recent studies have highlighted the role of high intensity, short-duration exercise as a time-efficient method to achieve both anaerobic and aerobic/endurance type adaptations. The factors that determine the fatigue profile of a muscle during intense exercise include muscle fiber composition, neuromuscular characteristics, high energy metabolite stores, buffering capacity, ionic regulation, capillarization, and mitochondrial density. Muscle fiber-type transformation during exercise training is usually toward the intermediate type IIA at the expense of both type I and IIx myosin heavy-chain isoforms. High-intensity training results in increases of both glycolytic and oxidative enzymes, muscle capillarization, improved phosphocreatine resynthesis and regulation of K+, H+, and lactate ions. Decreases of the habitual activity level due to injury or sedentary lifestyle result in partial or even compete reversal of the adaptations due to previous training, manifested by reductions in fiber cross-sectional area, decreased oxidative capacity, and capillarization. Complete immobilization due to injury results in markedly decreased force output and fatigue resistance. Muscle unloading reduces electromyographic activity and causes muscle atrophy and significant decreases in capillarization and oxidative enzymes activity. The last part of the review discusses the beneficial effects of intermittent high-intensity exercise training in patients with different health conditions to demonstrate the powerful effect of exercise on health and well being. PMID

  17. Comprehensive Management Strategies for Physical Inactivity in Youth

    Science.gov (United States)

    MYER, GREGORY D.; FAIGENBAUM, AVERY D.; STRACCIOLINI, ANDREA; HEWETT, TIMOTHY E.; MICHELI, LYLE J.; BEST, THOMAS M.

    2013-01-01

    Despite the widely recognized benefits of daily play, recreation, sports, and physical education on the physical and psychosocial well-being of children and adolescents, many contemporary children and adolescents worldwide do not meet the recommendations for daily physical activity. The decline in physical activity seems to start early in life which leads to conditions characterized by reduced levels of physical activity in the pediatric population that are inconsistent with current public health recommendations. Unlike many other diseases and disorders in pediatrics, physical inactivity in youth is unique in that it currently lacks a clinical gold standard for diagnosis. This makes the diagnosis and treatment medically challenging, though no less important, as the resultant ramifications of a missed diagnosis are of significant detriment. Exercise deficient children need to be identified early in life and treated with developmentally appropriate exercise programs designed to target movement deficiencies and physical weaknesses in a supportive environment. Without such interventions early in life, children are more likely to become resistant to our interventions later in life and consequently suffer from adverse health consequences. Integrative approaches that link health care professionals, pediatric exercise specialists, school administrators, community leaders, and policy makers, may provide the best opportunity to promote daily physical activity, reinforce desirable behaviors, and educate parents about the exercise-health link. If health care providers miss the window of opportunity to identify exercise deficit disorder in youth and promote healthy lifestyle choices, the eventual decline and disinterest in physical activity will begin to take shape and new health care concerns will continue to emerge. PMID:23851413

  18. 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.

  19. 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.

  20. Supertwistor connection and conformal supergravity

    International Nuclear Information System (INIS)

    Merkulov, S.A.

    1985-01-01

    Supersymmetry expansion of the geometry of local twistors is suggested. Definition of the space of local supertwistors is given and its differential geometry is formulated. Variational principles are discussed, and it is shown that corresponding Euler-Lagrange equations also coincide and result in superzero equations of N=1 conformal supergravitation, which generalize Bach equations

  1. 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...

  2. 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...

  3. Conformal symmetry and holographic cosmology

    NARCIS (Netherlands)

    Bzowski, A.W.

    2013-01-01

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

  4. Logarithmic conformal field theory: beyond an introduction

    Science.gov (United States)

    Creutzig, Thomas; Ridout, David

    2013-12-01

    of the underlying chiral algebra and the modular data pertaining to the characters of the representations. Each of the archetypal logarithmic conformal field theories is studied here by first determining its irreducible spectrum, which turns out to be continuous, as well as a selection of natural reducible, but indecomposable, modules. This is followed by a detailed description of how to obtain character formulae for each irreducible, a derivation of the action of the modular group on the characters, and an application of the Verlinde formula to compute the Grothendieck fusion rules. In each case, the (genuine) fusion rules are known, so comparisons can be made and favourable conclusions drawn. In addition, each example admits an infinite set of simple currents, hence extended symmetry algebras may be constructed and a series of bulk modular invariants computed. The spectrum of such an extended theory is typically discrete and this is how the triplet model \\mathfrak {W} (1,2) arises, for example. Moreover, simple current technology admits a derivation of the extended algebra fusion rules from those of its continuous parent theory. Finally, each example is concluded by a brief description of the computation of some bulk correlators, a discussion of the structure of the bulk state space, and remarks concerning more advanced developments and generalizations. The final part gives a very short account of the theory of staggered modules, the (simplest class of) representations that are responsible for the logarithmic singularities that distinguish logarithmic theories from their rational cousins. These modules are discussed in a generality suitable to encompass all the examples met in this review and some of the very basic structure theory is proven. Then, the important quantities known as logarithmic couplings are reviewed for Virasoro staggered modules and their role as fundamentally important parameters, akin to the three-point constants of rational conformal field

  5. Description of radiological problems at inactive uranium mill sites and formerly utilized MED/AEC sites

    Energy Technology Data Exchange (ETDEWEB)

    Jacobs, D.G.; Dickson, H.W.

    1979-02-01

    During the early years of development of the nuclear program in the United States, more than a hundred sites were used by the Manhattan Engineer District (MED), and the U.S. Atomic Energy Commission (AEC), and/or its uranium suppliers. Many of these sites are no longer used for such activities, but in many cases, the real estate remains contaminated with radioactivity and can be a potential source of exposure to members of the general public. In addition, 22 inactive uranium mill tailings sites exist in the western part of the United States. Radioactive contamination conditions range from slight contamination on the surfaces of buildings and equipment to extensive contamination of the subsoil. The Department of Energy is conducting a program to assure that adequate precautions are taken in the management of these properties to provide the cost-effective protection of public health while permitting further use of land and other resources. Several issues which should be considered in the development of an effective policy for long-term management of such properties are identified.

  6. Description of radiological problems at inactive uranium mill sites and formerly utilized MED/AEC sites

    International Nuclear Information System (INIS)

    Jacobs, D.G.; Dickson, H.W.

    1979-02-01

    During the early years of development of the nuclear program in the United States, more than a hundred sites were used by the Manhattan Engineer District (MED), and the U.S. Atomic Energy Commission (AEC), and/or its uranium suppliers. Many of these sites are no longer used for such activities, but in many cases, the real estate remains contaminated with radioactivity and can be a potential source of exposure to members of the general public. In addition, 22 inactive uranium mill tailings sites exist in the western part of the United States. Radioactive contamination conditions range from slight contamination on the surfaces of buildings and equipment to extensive contamination of the subsoil. The Department of Energy is conducting a program to assure that adequate precautions are taken in the management of these properties to provide the cost-effective protection of public health while permitting further use of land and other resources. Several issues which should be considered in the development of an effective policy for long-term management of such properties are identified

  7. Initial high-resolution microscopic mapping of active and inactive regulatory sequences proves non-random 3D arrangements in chromatin domain clusters.

    Science.gov (United States)

    Cremer, Marion; Schmid, Volker J; Kraus, Felix; Markaki, Yolanda; Hellmann, Ines; Maiser, Andreas; Leonhardt, Heinrich; John, Sam; Stamatoyannopoulos, John; Cremer, Thomas

    2017-08-07

    The association of active transcription regulatory elements (TREs) with DNAse I hypersensitivity (DHS[+]) and an 'open' local chromatin configuration has long been known. However, the 3D topography of TREs within the nuclear landscape of individual cells in relation to their active or inactive status has remained elusive. Here, we explored the 3D nuclear topography of active and inactive TREs in the context of a recently proposed model for a functionally defined nuclear architecture, where an active and an inactive nuclear compartment (ANC-INC) form two spatially co-aligned and functionally interacting networks. Using 3D structured illumination microscopy, we performed 3D FISH with differently labeled DNA probe sets targeting either sites with DHS[+], apparently active TREs, or DHS[-] sites harboring inactive TREs. Using an in-house image analysis tool, DNA targets were quantitatively mapped on chromatin compaction shaped 3D nuclear landscapes. Our analyses present evidence for a radial 3D organization of chromatin domain clusters (CDCs) with layers of increasing chromatin compaction from the periphery to the CDC core. Segments harboring active TREs are significantly enriched at the decondensed periphery of CDCs with loops penetrating into interchromatin compartment channels, constituting the ANC. In contrast, segments lacking active TREs (DHS[-]) are enriched toward the compacted interior of CDCs (INC). Our results add further evidence in support of the ANC-INC network model. The different 3D topographies of DHS[+] and DHS[-] sites suggest positional changes of TREs between the ANC and INC depending on their functional state, which might provide additional protection against an inappropriate activation. Our finding of a structural organization of CDCs based on radially arranged layers of different chromatin compaction levels indicates a complex higher-order chromatin organization beyond a dichotomic classification of chromatin into an 'open,' active and 'closed

  8. Inactive nurses in Taiwan: human capital, intention to return to hospital nursing, and incentives for returning.

    Science.gov (United States)

    Yu, Hsing-Yi; Tang, Fu-In; Chen, I-Ju; Yin, Teresa J C; Chen, Chu-Chieh; Yu, Shu

    2016-04-01

    To investigate inactive nurses' human capital, intention to return to hospital nursing and incentives for returning. Few studies have discussed the loss of human capital with regard to inactive nurses and how to attract them to return to clinical work. Systematic random sampling was used, with 328 subjects completing the mailed questionnaires, resulting in a response rate of 25.4%. Inactive nurses not only had moderate to high human capital (average years of nursing experience was 10.29, with moderate to high levels of nursing professional commitment and nursing competence) and were young. Forty-three percent of subjects reported intending to return to hospital nursing. Sufficient nurse staffing, greater safety in the working environment, and re-entry preparation programmes were incentives for returning. Recruiting inactive nurses back to hospital work is vital and feasible as inactive nurses had a moderate to high degree of human capital. The most feasible way is offering reasonable working conditions, in particular, providing sufficient staffing, a safe working environment and re-entry preparation programmes. The findings confirm the human capital of inactive nurses and provide concrete directions for nursing managers to follow when recruiting inactive nurses to hospital nursing. © 2015 John Wiley & Sons Ltd.

  9. The Comparing of Psychological Status of Active and Inactive Relief Workers in Traffic Accident in Red Cross of Karaj Township in 1391

    Directory of Open Access Journals (Sweden)

    N. Amini

    2013-10-01

    Full Text Available Background: Traffic accidents are major result of death and disability that their victims need relief Relief worker who do this, are at risk of psychological disorder because of Overwhelming accident and rescue work-related stress .It is necessary to be evaluated their psychological status for giving them psychological support. This study was conducted to compare the mental state in active and inactive relief workers in traffic accident in Karaj red cross in1391. Methods: This descriptive-analytic cross-sectional study was done among both of active and inactive relief worker in traffic accident in Karaj red cross. Data collection tool were demographic questionnaire and Standard questionnaire for measuring depression, anxiety and stress. Collected data was analysed by SPSS16. Results: Result showed that there is no significant difference between mean of depression, stress and anxiety score in both of them(P>0.05, also there is no significant relationship between psychological status with age, educational level, work backward and marital status but stress and marital status in inactive group was significant(P<0.05. Conclusion: It appears besides traffic accident relief worker, inactive relief worker need more attention and scale up psychological support programs and psychological disorder screening. Also it is proposed to do similar study in larger scale.

  10. When Action-Inaction Framing Leads to Higher Escalation of Commitment: A New Inaction-Effect Perspective on the Sunk-Cost Fallacy.

    Science.gov (United States)

    Feldman, Gilad; Wong, Kin Fai Ellick

    2018-04-01

    Escalation of commitment to a failing course of action occurs in the presence of (a) sunk costs, (b) negative feedback that things are deviating from expectations, and (c) a decision between escalation and de-escalation. Most of the literature to date has focused on sunk costs, yet we offer a new perspective on the classic escalation-of-commitment phenomenon by focusing on the impact of negative feedback. On the basis of the inaction-effect bias, we theorized that negative feedback results in the tendency to take action, regardless of what that action may be. In four experiments, we demonstrated that people facing escalation-decision situations were indeed action oriented and that framing escalation as action and de-escalation as inaction resulted in a stronger tendency to escalate than framing de-escalation as action and escalation as inaction (mini-meta-analysis effect d = 0.37, 95% confidence interval = [0.21, 0.53]).

  11. 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.

  12. Steganography in inactive frames of VoIP streams encoded by source codec

    OpenAIRE

    Huang, Yongfeng; Tang, Shanyu; Yuan, Jian

    2011-01-01

    This paper describes a novel high capacity steganography algorithm for embedding data in the inactive frames of low bit rate audio streams encoded by G.723.1 source codec, which is used extensively in Voice over Internet Protocol (VoIP). This study reveals that, contrary to existing thoughts, the inactive frames of VoIP streams are more suitable for data embedding than the active frames of the streams, that is, steganography in the inactive audio frames attains a larger data embedding capacit...

  13. The Pattern, Causes And Management of Student Non-Conforming ...

    African Journals Online (AJOL)

    The study examined the pattern and causes of non-conforming behaviours of students of secondary schools in Nigeria, as perceived by teachers. It also researched into the management of these behaviour by the teachers. Two hundred and forty secondary school teachers drawn from the four divisions of Ogun State, ...

  14. Multiple Conformations of Phosphodiesterase-5: Implications for Enzyme Function and Drug Developement

    Energy Technology Data Exchange (ETDEWEB)

    Wang,H.; Liu, Y.; Huai, Q.; Cai, J.; Zoraghi, R.; Francis, S.; Corbin, J.; Robinson, H.; Xin, Z.; et al.

    2006-01-01

    Phosphodiesterase-5 (PDE5) is the target for sildenafil, vardenafil, and tadalafil, which are drugs for treatment of erectile dysfunction and pulmonary hypertension. We report here the crystal structures of a fully active catalytic domain of unliganded PDE5A1 and its complexes with sildenafil or icarisid II. These structures together with the PDE5A1-isobutyl-1-methylxanthine complex show that the H-loop (residues 660-683) at the active site of PDE5A1 has four different conformations and migrates 7 to 35 Angstroms upon inhibitor binding. In addition, the conformation of sildenafil reported herein differs significantly from those in the previous structures of chimerically hybridized or almost inactive PDE5. Mutagenesis and kinetic analyses confirm that the H-loop is particularly important for substrate recognition and that invariant Gly659 which immediately precedes the H-loop is critical for optimal substrate affinity and catalytic activity.

  15. Regulation of β2-adrenergic receptor function by conformationally selective single-domain intrabodies

    DEFF Research Database (Denmark)

    Staus, Dean P; Wingler, Laura M; Strachan, Ryan T

    2014-01-01

    . However, a monomeric single-domain antibody (nanobody) from the Camelid family was recently found to allosterically bind and stabilize an active conformation of the β2-adrenergic receptor (β2AR). Here, we set out to study the functional interaction of 18 related nanobodies with the β2AR to investigate...... their roles as novel tools for studying GPCR biology. Our studies revealed several sequence-related nanobody families with preferences for active (agonist-occupied) or inactive (antagonist-occupied) receptors. Flow cytometry analysis indicates that all nanobodies bind to epitopes displayed...... on the intracellular receptor surface; therefore, we transiently expressed them intracellularly as "intrabodies" to test their effects on β2AR-dependent signaling. Conformational specificity was preserved after intrabody conversion as demonstrated by the ability for the intracellularly expressed nanobodies...

  16. Remedial Action Plan and site design for stabilization of the inactive uranium mill tailings site at Falls City, Texas

    International Nuclear Information System (INIS)

    Chernoff, A.R.; Lacker, D.K.

    1992-09-01

    The uranium processing site near Falls City, Texas, was one of 24 inactive uranium mill sites designated to be remediated by the US Department of Energy (DOE) under Title I of the Uranium Mill Tailings Radiation Control Act of 1978 (UMTRCA). The UMTRCA requires that the US Nuclear Regulatory Commission (NRC) concur with the DOE's remedial action plan (RAP) and certify that the remedial action conducted at the site complies with the standards promulgated by the US Environmental Protection Agency (EPA). The RAP, which includes this summary remedial action selection report (RAS), serves a two-fold purpose. First, it describes the activities proposed by the DOE to accomplish long-term stabilization and control of the residual radioactive materials at the inactive uranium processing site near Falls City, Texas. Second, this document and the remainder of the RAP, upon concurrence and execution by the DOE, the State of Texas, and the NRC, becomes Appendix B of the Cooperative Agreement between the DOE and the State of Texas

  17. Remedial action plan and site design for stabilization of the inactive uranium processing site at Naturita, Colorado

    International Nuclear Information System (INIS)

    1993-08-01

    The uranium processing site near Naturita, Colorado, is one of 24 inactive uranium mill sites designated to be cleaned up by the US Department of Energy (DOE) under the Uranium Mill Tailings Radiation Control Act of 1978 (UMTRCA), Public Law 95-604. Part of the UMTRCA requires that the US Nuclear Regulatory Commission (NRC) concur with the DOE's remedial action plan (RAP) and certify that the remedial action conducted at the site complies with the standards promulgated by the US Environmental Protection Agency (EPA). Included in the RAP is this Remedial Action Selection Report (RAS), which serves two purposes. First, it describes the activities that are proposed by the DOE to accomplish remediation and long-term stabilization and control of the radioactive materials at the inactive uranium processing site near Naturita, Colorado. Second, this document and the rest of the RAP, upon concurrence and execution by the DOE, the state of Colorado, and the NRC, become Appendix B of the cooperative agreement between the DOE and the State of Colorado

  18. Conformational Dynamics of apo-GlnBP Revealed by Experimental and Computational Analysis

    KAUST Repository

    Feng, Yitao

    2016-10-13

    The glutamine binding protein (GlnBP) binds l-glutamine and cooperates with its cognate transporters during glutamine uptake. Crystal structure analysis has revealed an open and a closed conformation for apo- and holo-GlnBP, respectively. However, the detailed conformational dynamics have remained unclear. Herein, we combined NMR spectroscopy, MD simulations, and single-molecule FRET techniques to decipher the conformational dynamics of apo-GlnBP. The NMR residual dipolar couplings of apo-GlnBP were in good agreement with a MD-derived structure ensemble consisting of four metastable states. The open and closed conformations are the two major states. This four-state model was further validated by smFRET experiments and suggests the conformational selection mechanism in ligand recognition of GlnBP. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

  19. Conformal invariance in the quantum field theory

    International Nuclear Information System (INIS)

    Kurak, V.

    1975-09-01

    Basic features concerning the present knowledge of conformal symmetry are illustrated in a simple model. Composite field dimensions of this model are computed and related to the conformal group. (author) [pt

  20. Remedial action plan for the inactive Uranium Processing Site at Naturita, Colorado. Remedial action plan: Attachment 2, Geology report, Attachment 3, Ground water hydrology report: Working draft

    International Nuclear Information System (INIS)

    1994-09-01

    The uranium processing site near Naturita, Colorado, is one of 24 inactive uranium mill sites designated to be cleaned up by the US Department of Energy (DOE) under the Uranium Mill Tailings Radiation Control Act of 1978 (UMTRCA), 42 USC section 7901 et seq. Part of the UMTRCA requires that the US Nuclear Regulatory Commission (NRC) concur with the DOE's remedial action plan (RAP) and certify that the remedial action conducted at the site complies with the standards promulgated by the US Environmental Protection Agency (EPA). This RAP serves two purposes. First, it describes the activities that are proposed by the DOE to accomplish remediation and long-term stabilization and control of the radioactive materials at the inactive uranium processing site near Naturita, Colorado. Second, this RAP, upon concurrence and execution by the DOE, the state of Colorado, and the NRC, become Appendix B of the cooperative agreement between the DOE and the state of Colorado

  1. Remedial action plan for the inactive Uranium Processing Site at Naturita, Colorado. Remedial action plan: Attachment 2, Geology report, Attachment 3, Ground water hydrology report: Working draft

    Energy Technology Data Exchange (ETDEWEB)

    1994-09-01

    The uranium processing site near Naturita, Colorado, is one of 24 inactive uranium mill sites designated to be cleaned up by the US Department of Energy (DOE) under the Uranium Mill Tailings Radiation Control Act of 1978 (UMTRCA), 42 USC {section}7901 et seq. Part of the UMTRCA requires that the US Nuclear Regulatory Commission (NRC) concur with the DOE`s remedial action plan (RAP) and certify that the remedial action conducted at the site complies with the standards promulgated by the US Environmental Protection Agency (EPA). This RAP serves two purposes. First, it describes the activities that are proposed by the DOE to accomplish remediation and long-term stabilization and control of the radioactive materials at the inactive uranium processing site near Naturita, Colorado. Second, this RAP, upon concurrence and execution by the DOE, the state of Colorado, and the NRC, become Appendix B of the cooperative agreement between the DOE and the state of Colorado.

  2. Applying conformational selection theory to improve crossdocking efficiency in 3-phosphoinositide dependent protein kinase-1.

    Science.gov (United States)

    Kotasthane, Anuja; Mulakala, Chandrika; Viswanadhan, Vellarkad N

    2014-03-01

    The emerging picture of biomolecular recognition is that of conformational selection followed by induced-fit. Conformational selection theory states that binding partners exist in various conformations in solution, with binding involving a "selection" between complementary conformers. In this study, we devise a docking protocol that mimics conformational selection in protein-ligand binding and demonstrate that it significantly enhances crossdocking accuracy over Glide's flexible docking protocol, which is widely used in the pharmaceutical industry. Our protocol uses a pregenerated conformational ensemble to simulate ligand flexibility. The ensemble was generated by thorough conformational sampling coupled with conformer minimization. The generated conformers were then rigidly docked in the active site of the protein along with a postdocking minimization step that allows limited induced fit effects to be modeled for the ligand. We illustrate the improved performance of our protocol through crossdocking of 31 ligands to cocomplexed proteins of the kinase 3-phosphoinositide dependent protein kinase-1 extracted from the crystal structures 1H1W (ATP bound), 1OKY (staurosporine bound) and 3QD0 (bound to a potent inhibitor). Consistent with conformational selection theory, the performance of our protocol was the best for crossdocking to the cognate protein bound to the natural ligand, ATP. Copyright © 2013 Wiley Periodicals, Inc.

  3. Anti-Inflammatory Effects of a Bout of Circuit Resistance Exercise With Moderateintensity in Inactive Obese Males

    Directory of Open Access Journals (Sweden)

    Asghari Jafarabadi

    2011-11-01

    Full Text Available Introduction: Obesity is a state characterized by a low-grade inflammation that leads to insulin resistance. The aim of the present study was to assess serum interleukin-18 (IL-18, interleukin-6 (IL-6, C-reactive protein (CRP and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR in response to circuit resistance exercise in obese and normal-weight subjects with different levels of physical activity. Methods: Thirty-two healthy male students participated in the present study. Subjects were divided into 4 groups according to their BMI and level of physical activity: active obese (n=8, active non-obese (n=8, inactive obese (n=8, and inactive non-obese (n=8. To determine serum IL-6, IL-18, CRP, glucose and insulin concentrations, fasting and post-exercise blood samples were obtained. Subjects performed a bout of circuit resistance exercise in 2 sets with 10 repetitions at 60% of 1RM. Results: Obese subjects comparing non-obese ones showed significant increase in IL-6 and significant decrease in IL-18 concentrations in response to exercise (p<0.05. There was no significant difference between active normal and inactive normal subjects in response to exercise. Also, there were not significant differences in four groups in response to exercise. Discussion: The significant decrease in IL-18 concentration in the obese group comparing normal group in response to exercise was probably due to anti-inflammatory effects of exercise. Also, recommending this kind of exercise for obese persons with low level of physical activity can improve insulin resistance.

  4. Peripheral brain-derived neurotrophic factor is related to cardiovascular risk factors in active and inactive elderly men

    Directory of Open Access Journals (Sweden)

    A. Zembron-Lacny

    2016-01-01

    Full Text Available Regular exercise plays an important preventive and therapeutic role in heart and vascular diseases, and beneficially affects brain function. In blood, the effects of exercise appear to be very complex and could include protection of vascular endothelial cells via neurotrophic factors and decreased oxidative stress. The purpose of this study was to identify the age-related changes in peripheral brain-derived neurotrophic factor (BDNF and its relationship to oxidative damage and conventional cardiovascular disease (CVD biomarkers, such as atherogenic index, C-reactive protein (hsCRP and oxidized LDL (oxLDL, in active and inactive men. Seventeen elderly males (61-80 years and 17 young males (20-24 years participated in this study. According to the 6-min Åstrand-Rhyming bike test, the subjects were classified into active and inactive groups. The young and elderly active men had a significantly better lipoprotein profile and antioxidant status, as well as reduced oxidative damage and inflammatory state. The active young and elderly men had significantly higher plasma BDNF levels compared to their inactive peers. BDNF was correlated with VO2max (r=0.765, P<0.001. In addition, we observed a significant inverse correlation of BDNF with atherogenic index (TC/HDL, hsCRP and oxLDL. The findings demonstrate that a high level of cardiorespiratory fitness reflected in VO2max was associated with a higher level of circulating BDNF, which in turn was related to common CVD risk factors and oxidative damage markers in young and elderly men.

  5. Modeling conformational ensembles of slow functional motions in Pin1-WW.

    Directory of Open Access Journals (Sweden)

    Faruck Morcos

    2010-12-01

    Full Text Available Protein-protein interactions are often mediated by flexible loops that experience conformational dynamics on the microsecond to millisecond time scales. NMR relaxation studies can map these dynamics. However, defining the network of inter-converting conformers that underlie the relaxation data remains generally challenging. Here, we combine NMR relaxation experiments with simulation to visualize networks of inter-converting conformers. We demonstrate our approach with the apo Pin1-WW domain, for which NMR has revealed conformational dynamics of a flexible loop in the millisecond range. We sample and cluster the free energy landscape using Markov State Models (MSM with major and minor exchange states with high correlation with the NMR relaxation data and low NOE violations. These MSM are hierarchical ensembles of slowly interconverting, metastable macrostates and rapidly interconverting microstates. We found a low population state that consists primarily of holo-like conformations and is a "hub" visited by most pathways between macrostates. These results suggest that conformational equilibria between holo-like and alternative conformers pre-exist in the intrinsic dynamics of apo Pin1-WW. Analysis using MutInf, a mutual information method for quantifying correlated motions, reveals that WW dynamics not only play a role in substrate recognition, but also may help couple the substrate binding site on the WW domain to the one on the catalytic domain. Our work represents an important step towards building networks of inter-converting conformational states and is generally applicable.

  6. The Madelung rule, Regge-like sequences and the conformal Lie algebra

    International Nuclear Information System (INIS)

    Campoamor-Stursberg, Rutwig

    2014-01-01

    The two main group theoretical models related to the Periodic System of Chemical Elements are reviewed, in connection with the Madelung rule and the construction of orthonormal bases of states for the conformal Lie algebra so (2,4). Basing on discrepancies between the Madelung rule and chemical experience, a new approach to the conformal symmetry, currently in development, is described

  7. 77 FR 11394 - Transportation Conformity Rule: MOVES Regional Grace Period Extension

    Science.gov (United States)

    2012-02-27

    ... has it been implemented to date? MOVES is EPA's state-of-the-art model for estimating emissions from... conformity rule, EPA articulated its intentions for establishing the length of a conformity grace period for... included his notes taken during an informal conversation with EPA staff that occurred prior to the...

  8. 46 CFR 386.5 - Conformity with signs and posted regulations.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 8 2010-10-01 2010-10-01 false Conformity with signs and posted regulations. 386.5 Section 386.5 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION MISCELLANEOUS REGULATIONS GOVERNING PUBLIC BUILDINGS AND GROUNDS AT THE UNITED STATES MERCHANT MARINE ACADEMY § 386.5 Conformity with...

  9. Two separable conformers of TATP and analogues exist at room temperature.

    Science.gov (United States)

    Denekamp, C; Gottlieb, L; Tamiri, T; Tsoglin, A; Shilav, R; Kapon, M

    2005-06-09

    [reaction: see text] TATP gives rise to two separable conformations because the barrier for interconversion between them is relatively high at room temperature. This kind of behavior is rare in cyclic organic systems and is the result of poor overlap in the "flip-flop" transition state. The crystal structure of the analogous tricyclohexanone triperoxide also indicates the presence of two conformers.

  10. 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.

  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. Conformal group actions and Segal's cosmology

    International Nuclear Information System (INIS)

    Werth, J.-E.

    1984-01-01

    A mathematical description of Segal's cosmological model in the framework of conformal group actions is presented. The relation between conformal and causal group actions on time-orientable Lorentzian manifolds is analysed and several examples are discussed. A criterion for the conformality of a map between Lorentzian manifolds is given. The results are applied to Segal's 'conformal compactification' of Minkowski space. Furthermore, the 'unitary formulation' of Segal's cosmology is regarded. (Author) [pt

  13. Stability of generic thin shells in conformally flat spacetimes

    Energy Technology Data Exchange (ETDEWEB)

    Amirabi, Z. [Eastern Mediterranean Univ., Gazimagusa (Turkey). Dept. of Physics

    2017-07-15

    Some important spacetimes are conformally flat; examples are the Robertson-Walker cosmological metric, the Einstein-de Sitter spacetime, and the Levi-Civita-Bertotti-Robinson and Mannheim metrics. In this paper we construct generic thin shells in conformally flat spacetime supported by a perfect fluid with a linear equation of state, i.e., p = ωσ. It is shown that, for the physical domain of ω, i.e., 0 < ω ≤ 1, such thin shells are not dynamically stable. The stability of the timelike thin shells with the Mannheim spacetime as the outer region is also investigated. (orig.)

  14. Conformal invariance in conditioned stochastic particle systems

    Science.gov (United States)

    Schütz, Gunter M.

    2017-08-01

    We consider space-time correlations in generic one-dimensional stochastic interacting particle systems with short-range interactions that undergo a fluctuation with an atypically activity of particle jumps or reactions or spin flips. We briefly review the approach in the framework of the quantum Hamiltonian formalism and present examples where the dynamics during such large fluctuations is governed not by the typical stationary dynamics, but by ballistic universality classes with dynamical exponent z=1 that are described unitary conformally invariant field theories with central charge c. For reaction-diffusion and spin flip dynamics we identify critical points (a) in the Ising universality class with c=1/2 , and (b) in the universality class of the three-states Potts model with c=4/5 . For the Ising universality class we obtain a universal scaling form for the generating function of cumulants of the jump activity. For repulsive driven diffusive systems with one conservation law the regime of an atypically high current or hopping activity is generically conformally invariant with central charge c=1 .

  15. Hyperbolic theory of relativistic conformal dissipative fluids

    Science.gov (United States)

    Lehner, Luis; Reula, Oscar A.; Rubio, Marcelo E.

    2018-01-01

    We develop a complete description of the class of conformal relativistic dissipative fluids of divergence form, following the formalism described in [R. Geroch and L. Lindblom, Phys. Rev. D 41, 1855 (1990), 10.1103/PhysRevD.41.1855, S. Pennisi, Some considerations on a non linear approach to extended thermodynamics and in Proceedings of Symposium of Kinetic Theory and Extended Thermodynamics, Bologna, 1987.]. This type of theory is fully described in terms of evolution variables whose dynamics are governed by total divergence-type conservation laws. Specifically, we give a characterization of the whole family of conformal fluids in terms of a single master scalar function defined up to second-order corrections in dissipative effects, which we explicitly find in general form. This allows us to identify the equilibrium states of the theory and derive constitutive relations and a Fourier-like law for the corresponding first-order theory heat flux. Finally, we show that among this class of theories—and near equilibrium configurations—there exist symmetric hyperbolic ones, implying that for them one can define well-posed initial value problems.

  16. Conformational transitions of a weak polyampholyte

    KAUST Repository

    Nair, Arun Kumar Narayanan

    2014-10-07

    Using grand canonical Monte Carlo simulations of a flexible polyelectrolyte where the charges are in contact with a reservoir of constant chemical potential given by the solution pH, we study the behavior of weak polyelectrolytes in poor and good solvent conditions for polymer backbone. We address the titration behavior and conformational properties of a flexible diblock polyampholyte chain formed of two oppositely charged weak polyelectrolyte blocks, each containing equal number of identical monomers. The change of solution pH induces charge asymmetry in a diblock polyampholyte. For diblock polyampholyte chains in poor solvents, we demonstrate that a discontinuous transition between extended (tadpole) and collapsed (globular) conformational states is attainable by varying the solution pH. The double-minima structure in the probability distribution of the free energy provides direct evidence for the first-order like nature of this transition. At the isoelectric point electrostatically driven coil-globule transition of diblock polyampholytes in good solvents is found to consist of different regimes identified with increasing electrostatic interaction strength. At pH values above or below the isoelectric point diblock chains are found to have polyelectrolyte-like behavior due to repulsion between uncompensated charges along the chain.

  17. 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.

  18. Integrability of conformal fishnet theory

    Science.gov (United States)

    Gromov, Nikolay; Kazakov, Vladimir; Korchemsky, Gregory; Negro, Stefano; Sizov, Grigory

    2018-01-01

    We study integrability of fishnet-type Feynman graphs arising in planar four-dimensional bi-scalar chiral theory recently proposed in arXiv:1512.06704 as a special double scaling limit of gamma-deformed N = 4 SYM theory. We show that the transfer matrix "building" the fishnet graphs emerges from the R-matrix of non-compact conformal SU(2 , 2) Heisenberg spin chain with spins belonging to principal series representations of the four-dimensional conformal group. We demonstrate explicitly a relationship between this integrable spin chain and the Quantum Spectral Curve (QSC) of N = 4 SYM. Using QSC and spin chain methods, we construct Baxter equation for Q-functions of the conformal spin chain needed for computation of the anomalous dimensions of operators of the type tr( ϕ 1 J ) where ϕ 1 is one of the two scalars of the theory. For J = 3 we derive from QSC a quantization condition that fixes the relevant solution of Baxter equation. The scaling dimensions of the operators only receive contributions from wheel-like graphs. We develop integrability techniques to compute the divergent part of these graphs and use it to present the weak coupling expansion of dimensions to very high orders. Then we apply our exact equations to calculate the anomalous dimensions with J = 3 to practically unlimited precision at any coupling. These equations also describe an infinite tower of local conformal operators all carrying the same charge J = 3. The method should be applicable for any J and, in principle, to any local operators of bi-scalar theory. We show that at strong coupling the scaling dimensions can be derived from semiclassical quantization of finite gap solutions describing an integrable system of noncompact SU(2 , 2) spins. This bears similarities with the classical strings arising in the strongly coupled limit of N = 4 SYM.

  19. Smart Conformists: Children and Adolescents Associate Conformity With Intelligence Across Cultures.

    Science.gov (United States)

    Wen, Nicole J; Clegg, Jennifer M; Legare, Cristine H

    2017-08-24

    The current study used a novel methodology based on multivocal ethnography to assess the relations between conformity and evaluations of intelligence and good behavior among Western (U.S.) and non-Western (Ni-Vanuatu) children (6- to 11-year-olds) and adolescents (13- to 17-year-olds; N = 256). Previous research has shown that U.S. adults were less likely to endorse high-conformity children as intelligent than Ni-Vanuatu adults. The current data demonstrate that in contrast to prior studies documenting cultural differences between adults' evaluations of conformity, children and adolescents in the United States and Vanuatu have a conformity bias when evaluating peers' intelligence and behavior. Conformity bias for good behavior increases with age. The results have implications for understanding the interplay of conformity bias and trait psychology across cultures and development. © 2017 The Authors. Child Development © 2017 Society for Research in Child Development, Inc.

  20. Using Two Disability Measures to Compare Physical Inactivity Among US Adults With Disabilities.

    Science.gov (United States)

    McGuire, Dana Olzenak; Watson, Kathleen B; Carroll, Dianna D; Courtney-Long, Elizabeth A; Carlson, Susan A

    2018-01-18

    Prevalence of health behaviors among adults with disabilities may vary by disability measure. We used data from the 2011-2015 National Health Interview Survey to estimate prevalence of physical inactivity by disability status using 2 measures of disability: Basic Actions Difficulty questions (BADQ) and a standard 6-question measure (6Q). Disability prevalence (BADQ, 31.1%; 6Q, 17.5%) and inactivity prevalence among adults with disability (BADQ, 42.9%; 6Q, 52.5%) and without disability (BADQ, 24.3%; 6Q, 26.2%) varied by measure; however, both measures highlight inactivity disparities for adults with disability. Disability measures influence physical inactivity estimates and are important for guiding surveillance and health promotion activities for adults with disabilities.

  1. Patterns of association between environmental quality and physical inactivity vary across the rural-urban continuum

    Science.gov (United States)

    Physical inactivity has been associated with numerous adverse health outcomes including obesity, heart disease, and depression, and is considered a major contributor to all-cause mortality worldwide. Many studies have shown associations between specific environmental features (la...

  2. 38 CFR 4.89 - Ratings for inactive nonpulmonary tuberculosis in effect on August 19, 1968.

    Science.gov (United States)

    2010-07-01

    ... Diseases, Immune Disorders and Nutritional Deficiencies § 4.89 Ratings for inactive nonpulmonary... the kidney and residuals of tuberculosis of the spine. Where there are existing pulmonary and...

  3. Recovering a Representative Conformational Ensemble from Underdetermined Macromolecular Structural Data

    Science.gov (United States)

    Berlin, Konstantin; Castañeda, Carlos A.; Schneidman-Duhovny, Dina; Sali, Andrej; Nava-Tudela, Alfredo; Fushman, David

    2013-01-01

    Structural analysis of proteins and nucleic acids is complicated by their inherent flexibility, conferred, for example, by linkers between their contiguous domains. Therefore, the macromolecule needs to be represented by an ensemble of conformations instead of a single conformation. Determining this ensemble is challenging because the experimental data are a convoluted average of contributions from multiple conformations. As the number of the ensemble degrees of freedom generally greatly exceeds the number of independent observables, directly deconvolving experimental data into a representative ensemble is an ill-posed problem. Recent developments in sparse approximations and compressive sensing have demonstrated that useful information can be recovered from underdetermined (ill-posed) systems of linear equations by using sparsity regularization. Inspired by these advances, we designed Sparse Ensemble Selection (SES) method for recovering multiple conformations from a limited number of observations. SES is more general and accurate than previously published minimum-ensemble methods, and we use it to obtain representative conformational ensembles of Lys48-linked di-ubiquitin, characterized by the residual dipolar coupling data measured at several pH conditions. These representative ensembles are validated against NMR chemical shift perturbation data and compared to maximum-entropy results. The SES method reproduced and quantified the previously observed pH dependence of the major conformation of Lys48-linked di-ubiquitin, and revealed lesser-populated conformations that are pre-organized for binding known di-ubiquitin receptors, thus providing insights into possible mechanisms of receptor recognition by polyubiquitin. SES is applicable to any experimental observables that can be expressed as a weighted linear combination of data for individual states. PMID:24093873

  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. Limit Cycles and Conformal Invariance

    CERN Document Server

    Fortin, Jean-Francois; Stergiou, Andreas

    2013-01-01

    There is a widely held belief that conformal field theories (CFTs) require zero beta functions. Nevertheless, the work of Jack and Osborn implies that the beta functions are not actually the quantites that decide conformality, but until recently no such behavior had been exhibited. Our recent work has led to the discovery of CFTs with nonzero beta functions, more precisely CFTs that live on recurrent trajectories, e.g., limit cycles, of the beta-function vector field. To demonstrate this we study the S function of Jack and Osborn. We use Weyl consistency conditions to show that it vanishes at fixed points and agrees with the generator Q of limit cycles on them. Moreover, we compute S to third order in perturbation theory, and explicitly verify that it agrees with our previous determinations of Q. A byproduct of our analysis is that, in perturbation theory, unitarity and scale invariance imply conformal invariance in four-dimensional quantum field theories. Finally, we study some properties of these new, "cycl...

  6. Electrophysiological precursors of social conformity

    Science.gov (United States)

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

    2013-01-01

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

  7. CONFORMITY IN CHRIST 1. THE TRANSFORMATION PROCESS

    African Journals Online (AJOL)

    This essay investigates the notion of conformity in Christ as it is part of a compre- hensive, multilayered process of transformation. In the first part it focuses on the process of transformation in creation, re-creation, conformity, love and glory. In the second part it discusses transformation in Christ by looking at conformation and ...

  8. Conformity in Christ | Waaijman | Acta Theologica

    African Journals Online (AJOL)

    This essay investigates the notion of conformity in Christ as it is part of a comprehensive, multilayered process of transformation. In the first part it focuses on the process of transformation in creation, re-creation, conformity, love and glory. In the second part it discusses transformation in Christ by looking at conformation and ...

  9. Structure of the Nanobody-Stabilized Active State of the Kappa Opioid Receptor.

    Science.gov (United States)

    Che, Tao; Majumdar, Susruta; Zaidi, Saheem A; Ondachi, Pauline; McCorvy, John D; Wang, Sheng; Mosier, Philip D; Uprety, Rajendra; Vardy, Eyal; Krumm, Brian E; Han, Gye Won; Lee, Ming-Yue; Pardon, Els; Steyaert, Jan; Huang, Xi-Ping; Strachan, Ryan T; Tribo, Alexandra R; Pasternak, Gavril W; Carroll, F Ivy; Stevens, Raymond C; Cherezov, Vadim; Katritch, Vsevolod; Wacker, Daniel; Roth, Bryan L

    2018-01-11

    The κ-opioid receptor (KOP) mediates the actions of opioids with hallucinogenic, dysphoric, and analgesic activities. The design of KOP analgesics devoid of hallucinatory and dysphoric effects has been hindered by an incomplete structural and mechanistic understanding of KOP agonist actions. Here, we provide a crystal structure of human KOP in complex with the potent epoxymorphinan opioid agonist MP1104 and an active-state-stabilizing nanobody. Comparisons between inactive- and active-state opioid receptor structures reveal substantial conformational changes in the binding pocket and intracellular and extracellular regions. Extensive structural analysis and experimental validation illuminate key residues that propagate larger-scale structural rearrangements and transducer binding that, collectively, elucidate the structural determinants of KOP pharmacology, function, and biased signaling. These molecular insights promise to accelerate the structure-guided design of safer and more effective κ-opioid receptor therapeutics. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Long-term sickness absence from work due to physical inactivity: A registry-based study.

    Science.gov (United States)

    Høgsbro, Cecilie; Davidsen, Michael; Sørensen, Jan

    2018-01-01

    The aim of this study was to explore the relationship between leisure-time physical inactivity and long-term sickness absence in a representative sample of individuals aged 16-54 years, within the labour market and in good health. It was hypothesised that physically inactive individuals have a higher risk of long-term sickness absence and longer duration of sickness absence. The study population was identified from the National Health and Morbidity Survey, 2010. Weekly data on long-term sickness absence were obtained from the National Register on Social Transfer Payments (the DREAM registry). The association of incidence and duration of long-term sickness absence with physical inactivity was explored using logistic and Poisson regression. Data were fitted to models with levels of physical activity, demographic, social and lifestyle characteristics as independent variables. A combined hurdle model was used to estimate the difference in mean number of absence weeks. Logistic regression showed that physically inactive individuals had a 27% higher incidence of long-term sickness absence compared with physically active individuals. The Poisson regression showed that long-term sickness absence was only slightly shorter (1 week less) for moderately active individuals compared with inactive individuals. The hurdle model estimated longer absence periods for inactive individuals (additional 2.5 weeks) in comparison with moderately and highly active individuals. The study showed that physically inactive individuals have a higher incidence of long-term absence and that physically inactive individuals have longer periods with sickness absence than moderately and highly active individuals. When adjustments for social and health behaviour were included, the estimated associations became statistically insignificant.

  11. Radium-226 in vegetation and substrates at inactive uranium mill sites

    International Nuclear Information System (INIS)

    Marple, M.L.

    1980-01-01

    Results of a study of the content of radium-226 in plants growing on inactive uranium mill tailings sites in the Four Corners Region of the southwestern United States and in plants grown under greenhouse conditions with minimal surficial contamination are reported. Field plant samples and associated substrates were analyzed from two carbonate tailings sites in the Grants Mineral Belt of New Mexico. Radium activities in air-cleaned samples ranged from 5 to 368 pCi/g (dry weight) depending on species and location: activities in plants growing on local soils averaged 1.0 pCi/g. The talings and local soils contain 140 to 1400 pCi/g and 2.1 pCi/g, respectively. An evaluation of cleaning methods on selected samples showed that from 17 to 79% of the radium activity measured in air-cleaned samples was due to surficial contamination, which varied with species and location. A survey of 18 inactive uranium mill sites in the Four Corners Region was performed. Radium activity in plant tissues from nine species ranged from 2 to 210 pCi/g on bare tailings and from 0.3 to 30 pCi/g on covered tailings The radium content in most of the soil overburdens on the covered tailings piles was 10 to 17 pCi/g. An experiment was performed to measure radium-226 uptake by two species grown on tailings covered with a shallow (5 cm) soil layer. A grass, Sporobolus airoides (alkali sacaton) and a shrub, Atriplex canescens (four-wing saltbush), were studied. The tailings were a mixture of sands and slimes from a carbonate pile. The tailings treatments were plants grown in a soil cover over tailings; the controls were plants grown only in soil. Three soil types, dune sand, clay loam, and loam, were used. The radium activity of the plant tissue from the tailings treatment compared to that of the appropriate control was 1 to 19 times greater for the grass and 4 to 27 times greater for the shrub

  12. Radium-226 in vegetation and substrates at inactive uranium mill sites

    Energy Technology Data Exchange (ETDEWEB)

    Marple, M.L.

    1980-01-01

    Results of a study of the content of radium-226 in plants growing on inactive uranium mill tailings sites in the Four Corners Region of the southwestern United States and in plants grown under greenhouse conditions with minimal surficial contamination are reported. Field plant samples and associated substrates were analyzed from two carbonate tailings sites in the Grants Mineral Belt of New Mexico. Radium activities in air-cleaned samples ranged from 5 to 368 pCi/g (dry weight) depending on species and location: activities in plants growing on local soils averaged 1.0 pCi/g. The talings and local soils contain 140 to 1400 pCi/g and 2.1 pCi/g, respectively. An evaluation of cleaning methods on selected samples showed that from 17 to 79% of the radium activity measured in air-cleaned samples was due to surficial contamination, which varied with species and location. A survey of 18 inactive uranium mill sites in the Four Corners Region was performed. Radium activity in plant tissues from nine species ranged from 2 to 210 pCi/g on bare tailings and from 0.3 to 30 pCi/g on covered tailings The radium content in most of the soil overburdens on the covered tailings piles was 10 to 17 pCi/g. An experiment was performed to measure radium-226 uptake by two species grown on tailings covered with a shallow (5 cm) soil layer. A grass, Sporobolus airoides (alkali sacaton) and a shrub, Atriplex canescens (four-wing saltbush), were studied. The tailings were a mixture of sands and slimes from a carbonate pile. The tailings treatments were plants grown in a soil cover over tailings; the controls were plants grown only in soil. Three soil types, dune sand, clay loam, and loam, were used. The radium activity of the plant tissue from the tailings treatment compared to that of the appropriate control was 1 to 19 times greater for the grass and 4 to 27 times greater for the shrub.

  13. Southern high latitude dune fields on Mars: Morphology, aeolian inactivity, and climate change

    Science.gov (United States)

    Fenton, L.K.; Hayward, R.K.

    2010-01-01

    In a study area spanning the martian surface poleward of 50?? S., 1190 dune fields have been identified, mapped, and categorized based on dune field morphology. Dune fields in the study area span ??? 116400km2, leading to a global dune field coverage estimate of ???904000km2, far less than that found on Earth. Based on distinct morphological features, the dune fields were grouped into six different classes that vary in interpreted aeolian activity level from potentially active to relatively inactive and eroding. The six dune field classes occur in specific latitude zones, with a sequence of reduced activity and degradation progressing poleward. In particular, the first signs of stabilization appear at ???60?? S., which broadly corresponds to the edge of high concentrations of water-equivalent hydrogen content (observed by the Neutron Spectrometer) that have been interpreted as ground ice. This near-surface ground ice likely acts to reduce sand availability in the present climate state on Mars, stabilizing high latitude dunes and allowing erosional processes to change their morphology. As a result, climatic changes in the content of near-surface ground ice are likely to influence the level of dune activity. Spatial variation of dune field classes with longitude is significant, suggesting that local conditions play a major role in determining dune field activity level. Dune fields on the south polar layered terrain, for example, appear either potentially active or inactive, indicating that at least two generations of dune building have occurred on this surface. Many dune fields show signs of degradation mixed with crisp-brinked dunes, also suggesting that more than one generation of dune building has occurred since they originally formed. Dune fields superposed on early and late Amazonian surfaces provide potential upper age limits of ???100My on the south polar layered deposits and ???3Ga elsewhere at high latitudes. No craters are present on any identifiable dune

  14. Rethinking exercise identity: a qualitative study of physically inactive cancer patients' transforming process while undergoing chemotherapy.

    Science.gov (United States)

    Adamsen, Lis; Andersen, Christina; Lillelund, Christian; Bloomquist, Kira; Møller, Tom

    2017-08-23

    To explore physically inactive breast and colon cancer patients' prediagnosis exercise history and attitudes to physical activity (PA) and experiences in initiating PA while undergoing adjuvant chemotherapy. An explorative qualitative study guided the interpretive analysis of semistructured, open-ended interviews conducted at initiation of chemotherapy and after 12 weeks. The study was embedded in a pilot randomised controlled trial. Participants were recruited from the Oncological Department at a hospital in Copenhagen, Denmark. 33 patients with cancer, median age 49 years: 25 patients with breast cancer and 8 with colon cancer, 72% with a low cardiac respiratory fitness level and the majority with a high level of education. Patients received adjuvant chemotherapy, oncologist's PA recommendation and exercise, cancer nurse specialist's counselling prior to allocation to PA interventions or waitlist control group. Prediagnosis exercise had been excluded from patients' daily lives due to perceptions of exercise as boring, lack of discipline and stressful work conditions for both genders. Recommendations from oncologists and nurses inspired the patients to reconsider their attitudes and behaviour by accepting recruitment and participation in PA interventions during chemotherapy. Despite extensive side effects, most patients adhered to their PA commitment due to their perception of the bodily, emotional and social benefits and support of healthcare professionals, peers and family. The patients' attitude towards exercise transformed from having no priority in patients' daily lives prediagnosis to being highly prioritised. This study identified four important phases in the exercise transformation process during the patients' treatment trajectory of relevance to clinicians in identifying, motivating and supporting physically inactive patients with cancer at long-term risk. Clinicians should address young, highly educated patients with cancer at onset of adjuvant

  15. Identification of potential small molecule allosteric modulator sites on IL-1R1 ectodomain using accelerated conformational sampling method.

    Directory of Open Access Journals (Sweden)

    Chao-Yie Yang

    Full Text Available The interleukin-1 receptor (IL-1R is the founding member of the interleukin 1 receptor family which activates innate immune response by its binding to cytokines. Reports showed dysregulation of cytokine production leads to aberrant immune cells activation which contributes to auto-inflammatory disorders and diseases. Current therapeutic strategies focus on utilizing antibodies or chimeric cytokine biologics. The large protein-protein interaction interface between cytokine receptor and cytokine poses a challenge in identifying binding sites for small molecule inhibitor development. Based on the significant conformational change of IL-1R type 1 (IL-1R1 ectodomain upon binding to different ligands observed in crystal structures, we hypothesized that transient small molecule binding sites may exist when IL-1R1 undergoes conformational transition and thus suitable for inhibitor development. Here, we employed accelerated molecular dynamics (MD simulation to efficiently sample conformational space of IL-1R1 ectodomain. Representative IL-1R1 ectodomain conformations determined from the hierarchy cluster analysis were analyzed by the SiteMap program which leads to identify small molecule binding sites at the protein-protein interaction interface and allosteric modulator locations. The cosolvent mapping analysis using phenol as the probe molecule further confirms the allosteric modulator site as a binding hotspot. Eight highest ranked fragment molecules identified from in silico screening at the modulator site were evaluated by MD simulations. Four of them restricted the IL-1R1 dynamical motion to inactive conformational space. The strategy from this study, subject to in vitro experimental validation, can be useful to identify small molecule compounds targeting the allosteric modulator sites of IL-1R and prevent IL-1R from binding to cytokine by trapping IL-1R in inactive conformations.

  16. Identification of potential small molecule allosteric modulator sites on IL-1R1 ectodomain using accelerated conformational sampling method.

    Science.gov (United States)

    Yang, Chao-Yie

    2015-01-01

    The interleukin-1 receptor (IL-1R) is the founding member of the interleukin 1 receptor family which activates innate immune response by its binding to cytokines. Reports showed dysregulation of cytokine production leads to aberrant immune cells activation which contributes to auto-inflammatory disorders and diseases. Current therapeutic strategies focus on utilizing antibodies or chimeric cytokine biologics. The large protein-protein interaction interface between cytokine receptor and cytokine poses a challenge in identifying binding sites for small molecule inhibitor development. Based on the significant conformational change of IL-1R type 1 (IL-1R1) ectodomain upon binding to different ligands observed in crystal structures, we hypothesized that transient small molecule binding sites may exist when IL-1R1 undergoes conformational transition and thus suitable for inhibitor development. Here, we employed accelerated molecular dynamics (MD) simulation to efficiently sample conformational space of IL-1R1 ectodomain. Representative IL-1R1 ectodomain conformations determined from the hierarchy cluster analysis were analyzed by the SiteMap program which leads to identify small molecule binding sites at the protein-protein interaction interface and allosteric modulator locations. The cosolvent mapping analysis using phenol as the probe molecule further confirms the allosteric modulator site as a binding hotspot. Eight highest ranked fragment molecules identified from in silico screening at the modulator site were evaluated by MD simulations. Four of them restricted the IL-1R1 dynamical motion to inactive conformational space. The strategy from this study, subject to in vitro experimental validation, can be useful to identify small molecule compounds targeting the allosteric modulator sites of IL-1R and prevent IL-1R from binding to cytokine by trapping IL-1R in inactive conformations.

  17. Consequences, norms, and generalized inaction in moral dilemmas: The CNI model of moral decision-making.

    Science.gov (United States)

    Gawronski, Bertram; Armstrong, Joel; Conway, Paul; Friesdorf, Rebecca; Hütter, Mandy

    2017-09-01

    Research on moral dilemma judgments has been fundamentally shaped by the distinction between utilitarianism and deontology. According to the principle of utilitarianism, the moral status of behavioral options depends on their consequences; the principle of deontology states that the moral status of behavioral options depends on their consistency with moral norms. To identify the processes underlying utilitarian and deontological judgments, researchers have investigated responses to moral dilemmas that pit one principle against the other (e.g., trolley problem). However, the conceptual meaning of responses in this paradigm is ambiguous, because the central aspects of utilitarianism and deontology-consequences and norms-are not manipulated. We illustrate how this shortcoming undermines theoretical interpretations of empirical findings and describe an alternative approach that resolves the ambiguities of the traditional paradigm. Expanding on this approach, we present a multinomial model that allows researchers to quantify sensitivity to consequences (C), sensitivity to moral norms (N), and general preference for inaction versus action irrespective of consequences and norms (I) in responses to moral dilemmas. We present 8 studies that used this model to investigate the effects of gender, cognitive load, question framing, and psychopathy on moral dilemma judgments. The findings obtained with the proposed CNI model offer more nuanced insights into the determinants of moral dilemma judgments, calling for a reassessment of dominant theoretical assumptions. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  18. Growth, metabolism and physiological response of the sea cucumber, Apostichopus japonicus Selenka during periods of inactivity

    Science.gov (United States)

    Du, Rongbin; Zang, Yuanqi; Tian, Xiangli; Dong, Shuanglin

    2013-03-01

    The growth, metabolism and physiological response of the sea cucumber, Apostichopus japonicus, were investigated during periods of inactivity. The body weight, oxygen consumption rate (OCR), activities of acidic phosphatase (ACP), alkaline phosphatase (AKP), catalase (CAT) and superoxide dismutase (SOD), and content of heat shock protein 70 (Hsp70) in the body wall and coelomic fluid of A. japonicus were measured during starvation, experimental aestivation and aestivation. The results showed that the body weight of sea cucumber in the three treatments decreased significantly during the experimental period ( P < 0.05). The OCR of sea cucumber reduced in starvation and experimental aestivation treatments, but increased gradually in natural aestivation treatment. The activities of ACP and AKP of sea cucumber decreased gradually in all treatments, whereas those of SOD and CAT as well as Hsp70 content decreased in the starvation and experimental aestivation treatments and increased in natural aestivation treatment. The sea cucumber entered a state of aestivation at 24°C. To some extent, the animals in experimental aestivation were different from those in natural aestivation in metabolism and physiological response. These findings suggested that the aestivation mechanism of A. japonicus is complex and may not be attributed to the elevated temperature only.

  19. Decision-tree approach to evaluating inactive uranium-processing sites for liner requirements

    International Nuclear Information System (INIS)

    Relyea, J.F.

    1983-03-01

    Recently, concern has been expressed about potential toxic effects of both radon emission and release of toxic elements in leachate from inactive uranium mill tailings piles. Remedial action may be required to meet disposal standards set by the states and the US Environmental Protection Agency (EPA). In some cases, a possible disposal option is the exhumation and reburial (either on site or at a new location) of tailings and reliance on engineered barriers to satisfy the objectives established for remedial actions. Liners under disposal pits are the major engineered barrier for preventing contaminant release to ground and surface water. The purpose of this report is to provide a logical sequence of action, in the form of a decision tree, which could be followed to show whether a selected tailings disposal design meets the objectives for subsurface contaminant release without a liner. This information can be used to determine the need and type of liner for sites exhibiting a potential groundwater problem. The decision tree is based on the capability of hydrologic and mass transport models to predict the movement of water and contaminants with time. The types of modeling capabilities and data needed for those models are described, and the steps required to predict water and contaminant movement are discussed. A demonstration of the decision tree procedure is given to aid the reader in evaluating the need for the adequacy of a liner

  20. Intramolecular Conformational Changes Optimize Protein Kinase C Signaling#

    Science.gov (United States)

    Antal, Corina E.; Violin, Jonathan D.; Kunkel, Maya T.; Skovsø, Søs

    2014-01-01

    Summary Optimal tuning of enzyme signaling is critical for cellular homeostasis. We use fluorescence resonance energy transfer reporters in live cells to follow conformational transitions that tune the affinity of a multi-domain signal transducer, protein kinase C, for optimal response to second messengers. This enzyme comprises two diacylglycerol sensors, the C1A and C1B domains, whose intrinsic affinity for ligand is sufficiently high that the enzyme would be in a ligand-engaged, active state if not for mechanisms that mask its domains. We show that both diacylglycerol sensors are exposed in newly-synthesized protein kinase C and that conformational transitions following priming phosphorylations mask the domains such that the lower affinity sensor, the C1B domain, is the primary diacylglycerol binder. Protein kinase C's conformational rearrangements serve as a paradigm for how multi-module transducers optimize their dynamic range of signaling. PMID:24631122

  1. Effect of physical inactivity on major noncommunicable diseases and life expectancy in Brazil.

    Science.gov (United States)

    de Rezende, Leandro Fornias Machado; Rabacow, Fabiana Maluf; Viscondi, Juliana Yukari Kodaira; Luiz, Olinda do Carmo; Matsudo, Victor Keihan Rodrigues; Lee, I-Min

    2015-03-01

    In Brazil, one-fifth of the population reports not doing any physical activity. This study aimed to assess the impact of physical inactivity on major noncommunicable diseases (NCDs), all-cause mortality and life expectancy in Brazil, by region and sociodemographic profile. We estimated the population attributable fraction (PAF) for physical inactivity associated with coronary heart disease, type 2 diabetes, breast cancer, colon cancer, and all-cause mortality. To calculate the PAF, we used the physical inactivity prevalence from the 2008 Brazilian Household Survey and relative risk data in the literature. In Brazil, physical inactivity is attributable to 3% to 5% of all major NCDs and 5.31% of all-cause mortality, ranging from 5.82% in the southeastern region to 2.83% in the southern region. Eliminating physical inactivity would increase the life expectancy by an average of 0.31 years. This reduction would affect mainly individuals with ≥ 15 years of schooling, male, Asian, elderly, residing in an urban area and earning ≥ 2 times the national minimum wage. In Brazil, physical inactivity has a major impact on NCDs and mortality, principally in the southeastern and central-west regions. Public policies and interventions promoting physical activity will significantly improve the health of the population.

  2. Physical inactivity and sedentary behavior: Overlooked risk factors in autoimmune rheumatic diseases?

    Science.gov (United States)

    Pinto, Ana Jéssica; Roschel, Hamilton; de Sá Pinto, Ana Lúcia; Lima, Fernanda Rodrigues; Pereira, Rosa Maria Rodrigues; Silva, Clovis Artur; Bonfá, Eloisa; Gualano, Bruno

    2017-07-01

    This review aims to (1) summarize the estimates of physical inactivity and sedentary behavior in autoimmune rheumatic diseases; (2) describe the relationship between physical (in)activity levels and disease-related outcomes; (3) contextualize the estimates and impact of physical inactivity and sedentary behavior in autoimmune diseases compared to other rheumatic diseases and chronic conditions; and (4) discuss scientific perspectives around this theme and potential clinical interventions to attenuate these preventable risk factors. We compiled evidence to show that estimates of physical inactivity and sedentary behavior in autoimmune rheumatic diseases are generally comparable to other rheumatic diseases as well as to other chronic conditions (e.g., type 2 diabetes, cardiovascular diseases, and obesity), in which a lack of physical activity and excess of sedentary behavior are well-known predictors of morbimortality. In addition, we also showed evidence that both physical inactivity and sedentary behavior may be associated with poor health-related outcomes (e.g., worse disease symptoms and low functionality) in autoimmune rheumatic diseases. Thus, putting into practice interventions to make the patients "sit less and move more", particularly light-intensity activities and/or breaking-up sedentary time, is a simple and prudent therapeutic approach to minimize physical inactivity and sedentary behavior, which are overlooked yet modifiable risk factors in the field of autoimmune rheumatic diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. HAMP domain conformers that propagate opposite signals in bacterial chemoreceptors.

    Directory of Open Access Journals (Sweden)

    Michael V Airola

    Full Text Available HAMP domains are signal relay modules in >26,000 receptors of bacteria, eukaryotes, and archaea that mediate processes involved in chemotaxis, pathogenesis, and biofilm formation. We identify two HAMP conformations distinguished by a four- to two-helix packing transition at the C-termini that send opposing signals in bacterial chemoreceptors. Crystal structures of signal-locked mutants establish the observed structure-to-function relationships. Pulsed dipolar electron spin resonance spectroscopy of spin-labeled soluble receptors active in cells verify that the crystallographically defined HAMP conformers are maintained in the receptors and influence the structure and activity of downstream domains accordingly. Mutation of HR2, a key residue for setting the HAMP conformation and generating an inhibitory signal, shifts HAMP structure and receptor output to an activating state. Another HR2 variant displays an inverted response with respect to ligand and demonstrates the fine energetic balance between "on" and "off" conformers. A DExG motif found in membrane proximal HAMP domains is shown to be critical for responses to extracellular ligand. Our findings directly correlate in vivo signaling with HAMP structure, stability, and dynamics to establish a comprehensive model for HAMP-mediated signal relay that consolidates existing views on how conformational signals propagate in receptors. Moreover, we have developed a rational means to manipulate HAMP structure and function that may prove useful in the engineering of bacterial taxis responses.

  4. Frustration-guided motion planning reveals conformational transitions in proteins.

    Science.gov (United States)

    Budday, Dominik; Fonseca, Rasmus; Leyendecker, Sigrid; van den Bedem, Henry

    2017-10-01

    Proteins exist as conformational ensembles, exchanging between substates to perform their function. Advances in experimental techniques yield unprecedented access to structural snapshots of their conformational landscape. However, computationally modeling how proteins use collective motions to transition between substates is challenging owing to a rugged landscape and large energy barriers. Here, we present a new, robotics-inspired motion planning procedure called dCC-RRT that navigates the rugged landscape between substates by introducing dynamic, interatomic constraints to modulate frustration. The constraints balance non-native contacts and flexibility, and instantaneously redirect the motion towards sterically favorable conformations. On a test set of eight proteins determined in two conformations separated by, on average, 7.5 Å root mean square deviation (RMSD), our pathways reduced the Cα atom RMSD to the goal conformation by 78%, outperforming peer methods. We then applied dCC-RRT to examine how collective, small-scale motions of four side-chains in the active site of cyclophilin A propagate through the protein. dCC-RRT uncovered a spatially contiguous network of residues linked by steric interactions and collective motion connecting the active site to a recently proposed, non-canonical capsid binding site 25 Å away, rationalizing NMR and multi-temperature crystallography experiments. In all, dCC-RRT can reveal detailed, all-atom molecular mechanisms for small and large amplitude motions. Source code and binaries are freely available at https://github.com/ExcitedStates/KGS/. © 2017 Wiley Periodicals, Inc.

  5. Flap Conformations in HIV-1 Protease are Altered by Mutations

    Science.gov (United States)

    Fanucci, Gail; Blackburn, Mandy; Veloro, Angelo; Galiano, Luis; Fangu, Ding; Simmerling, Carlos

    2009-03-01

    HIV-1 protease (PR) is an enzyme that is a major drug target in the treatment of AIDS. Although the structure and function of HIV-1 PR have been studied for over 20 years, questions remain regarding the conformations and dynamics of the β-hairpin turns (flaps) that cover the active site cavity. Distance measurements with pulsed EPR spectroscopy of spin labeled constructs of HIV-1 PR have been used to characterize the flap conformations in the apo and inhibitor bound states. From the most probably distances and the breadth of the distance distribution profiles from analysis of the EPR data, insights regarding the flap conformations and flexibility are gained. The EPR results clearly show how drug pressure selected mutations alter the average conformation of the flaps and the degree of opening of the flaps. Molecular dynamics simulations successfully regenerate the experimentally determined distance distribution profiles, and more importantly, provide structural models for full interpretation of the EPR results. By combining experiment and theory to understand the role that altered flap flexibility/conformations play in the mechanism of drug resistance, key insights are gained toward the rational development of new inhibitors of this important enzyme.

  6. Brownian dynamics simulation of the cross-talking effect among modified histones on conformations of nucleosomes

    Science.gov (United States)

    Duan, Zhao-Wen; Li, Wei; Xie, Ping; Dou, Shuo-Xing; Wang, Peng-Ye

    2010-04-01

    Using Brownian dynamics simulation, we studied the effect of histone modifications on conformations of an array of nucleosomes in a segment of chromatin. The simulation demonstrated that the segment of chromatin shows the dynamic behaviour that its conformation can switch between a state with nearly all of the histones being wrapped by DNA and a state with nearly all of the histones being unwrapped by DNA, thus involving the “cross-talking" interactions among the histones. Each state can stay for a sufficiently long time. These conformational states are essential for gene expression or gene silence. The simulation also shows that these conformational states can be inherited by the daughter DNAs during DNA replication, giving a theoretical explanation of the epigenetic phenomenon.

  7. Brownian dynamics simulation of the cross-talking effect among modified histones on conformations of nucleosomes

    International Nuclear Information System (INIS)

    Zhao-Wen, Duan; Wei, Li; Ping, Xie; Shuo-Xing, Dou; Peng-Ye, Wang

    2010-01-01

    Using Brownian dynamics simulation, we studied the effect of histone modifications on conformations of an array of nucleosomes in a segment of chromatin. The simulation demonstrated that the segment of chromatin shows the dynamic behaviour that its conformation can switch between a state with nearly all of the histones being wrapped by DNA and a state with nearly all of the histones being unwrapped by DNA, thus involving the “cross-talking” interactions among the histones. Each state can stay for a sufficiently long time. These conformational states are essential for gene expression or gene silence. The simulation also shows that these conformational states can be inherited by the daughter DNAs during DNA replication, giving a theoretical explanation of the epigenetic phenomenon. (cross-disciplinary physics and related areas of science and technology)

  8. Remedial Action Plan and site conceptual design for stabilization of the inactive uranium mill tailings site at Spook, Wyoming

    Energy Technology Data Exchange (ETDEWEB)

    Matthews, M L [USDOE Albuquerque Operations Office, NM (United States). Uranium Mill Tailings Remedial Action Project Office; Sullivan, M [Wyoming State Government, Cheyenne, WY (United States)

    1990-04-01

    This Remedial Action Plan (RAP) has been developed to serve a threefold purpose. It presents the series of activities which are proposed by the US Department of Energy (DOE) to accomplish long-term stabilization and control of radioactive materials at an inactive uranium processing site northeast of Casper, Wyoming, and referred to as the Spook site. It provides a characterization of the present conditions at the site and also serves to document the concurrence of the State of Wyoming and the US Nuclear Regulatory Commission (NRC) in the remedial action. This agreement, upon execution by the DOE and the State of Wyoming, and concurrence by the NRC, becomes Appendix B of the Cooperative Agreement.

  9. Remedial Action Plan for stabilization of the inactive uraniferous lignite processing sites at Belfield and Bowman, North Dakota

    International Nuclear Information System (INIS)

    1990-12-01

    This remedial action plan (RAP) has been developed to serve a threefold purpose. It presents the series of activities that are proposed by the US Department of Energy (DOE) to accomplish long-term stabilization and control of radioactive materials at the inactive uraniferous lignite processing sites at Belfield and near Bowman (at the former Griffin town site), North Dakota. It provides a characterization of the present conditions of the sites. It also serves to document the concurrence of the state of North Dakota and the US Nuclear Regulatory Commission (NRC) in the remedial action. This agreement, upon execution by the DOE and the state of North Dakota and concurrence by the NRC, becomes Appendix B of the Cooperative Agreement

  10. Remedial Action Plan and site conceptual design for stabilization of the inactive uranium mill tailings site at Spook, Wyoming

    International Nuclear Information System (INIS)

    Matthews, M.L.

    1990-04-01

    This Remedial Action Plan (RAP) has been developed to serve a threefold purpose. It presents the series of activities which are proposed by the US Department of Energy (DOE) to accomplish long-term stabilization and control of radioactive materials at an inactive uranium processing site northeast of Casper, Wyoming, and referred to as the Spook site. It provides a characterization of the present conditions at the site and also serves to document the concurrence of the State of Wyoming and the US Nuclear Regulatory Commission (NRC) in the remedial action. This agreement, upon execution by the DOE and the State of Wyoming, and concurrence by the NRC, becomes Appendix B of the Cooperative Agreement

  11. Multiple Conformations of Gal3 Protein Drive the Galactose-Induced Allosteric Activation of the GAL Genetic Switch of Saccharomyces cerevisiae.

    Science.gov (United States)

    Kar, Rajesh Kumar; Kharerin, Hungyo; Padinhateeri, Ranjith; Bhat, Paike Jayadeva

    2017-01-06

    Gal3p is an allosteric monomeric protein that activates the GAL genetic switch of Saccharomyces cerevisiae in response to galactose. Expression of constitutive mutant of Gal3p or overexpression of wild-type Gal3p activates the GAL switch in the absence of galactose. These data suggest that Gal3p exists as an ensemble of active and inactive conformations. Structural data have indicated that Gal3p exists in open (inactive) and closed (active) conformations. However, a mutant of Gal3p that predominantly exists in inactive conformation and is yet capable of responding to galactose has not been isolated. To understand the mechanism of allosteric transition, we have isolated a triple mutant of Gal3p with V273I, T404A, and N450D substitutions, which, upon overexpression, fails to activate the GAL switch on its own but activates the switch in response to galactose. Overexpression of Gal3p mutants with single or double mutations in any of the three combinations failed to exhibit the behavior of the triple mutant. Molecular dynamics analysis of the wild-type and the triple mutant along with two previously reported constitutive mutants suggests that the wild-type Gal3p may also exist in super-open conformation. Furthermore, our results suggest that the dynamics of residue F237 situated in the hydrophobic pocket located in the hinge region drives the transition between different conformations. Based on this study, we suggest that conformational selection mechanism is the driving force in the allosteric transition of Gal3p, which may have implications in other signaling pathways involving monomeric proteins. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. The solid-state and solution-state reassigned structures of tagitinin A, a 3,10-epoxy-germacrolide from Tithonia diversifolia, and the interconversion of 3,10-epoxy-germacrolide conformational families via a ring-atom flip mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Glaser, Robert [Ben-Gurion University of the Negev (Israel). Dept. of Chemistry]. E-mail: rglaser@bgumail.bgu.ac.il; Garcia, Abraham; Chavez, Maria Isabel; Delgado, Guillermo [Universidad Nacional Autonoma de Mexico, Mexico, D.F. (Mexico). Inst. de Quimica]. E-mail: delgado@servidor.unam.mx

    2005-05-15

    Tagitinin A (2), a known 3,10-epoxy-germacrolide-6,7-trans-lactone isolated from Tithonia diversifolia, was investigated by single crystal X-ray diffraction analysis. It was found to have a 1{beta},4{alpha},6{alpha},7{beta},8{beta} relative configuration which differed at C(1) from the 1a-orientation originally reported in the literature which was determined by Horeau's Rule. Analysis of the 1H NMR spectrum of 2 shows the molecule to maintain its crystallographically observed twist-chair-boat (TCB) nine-membered ring conformation in acetone-d6 solution. The twist-chair-boat/skew-chair-boat type 3 conformations of saturated/unsaturated nine-membered rings within 3,10-epoxy-germacrolides can be interconverted to the skew-chair-chair (SCC) conformation by means of a C(9) ring atom flip mechanism. As a result of this conformational change, the orientation of the C(1) atom and the C(8)-oxycarbonyl moiety are transformed from diequatorial to diaxial. The reported stereochemistry of 3,10-epoxy-germacrolide lactone structures, and the DFT B3LYP/6-31g(d) modeling findings in this work indicate that tetrahedral C(1) atoms stabilize the TCB/SCB type 3 conformations, while their trigonal counterparts stabilize the SCC conformation. (author)

  13. Conformal nature of the Hawking radiation

    International Nuclear Information System (INIS)

    Materassi, M.

    2000-01-01

    String theory usually represents quantum black holes as systems whose statistical mechanics reproduces Hawking's thermodynamics in a very satisfactory way. Complicated brane theoretical models are worked out, as quantum versions of Supergravity solutions. These models are then assumed to be in thermal equilibrium: this is a little cheating, because one is looking for an explanation of the seeming thermodynamical nature of black holes, so they cannot be assumed to be finite temperature systems! In the model presented here, the black body spectrum arises with no statistical hypothesis as an approximation of the unitary evolution of microscopic black holes, which are always described by a 1+1 conformal field theory, characterized by some Virasoro algebra. At the end, one can state that the Hawking-thermodynamics of the system is a by-product of the algebraic Virasoro-symmetric nature of the event horizon. This is the central result of the present work. (author)

  14. Conformal bootstrap, universality and gravitational scattering

    Directory of Open Access Journals (Sweden)

    Steven Jackson

    2015-12-01

    Full Text Available We use the conformal bootstrap equations to study the non-perturbative gravitational scattering between infalling and outgoing particles in the vicinity of a black hole horizon in AdS. We focus on irrational 2D CFTs with large c and only Virasoro symmetry. The scattering process is described by the matrix element of two light operators (particles between two heavy states (BTZ black holes. We find that the operator algebra in this regime is (i universal and identical to that of Liouville CFT, and (ii takes the form of an exchange algebra, specified by an R-matrix that exactly matches the scattering amplitude of 2+1 gravity. The R-matrix is given by a quantum 6j-symbol and the scattering phase by the volume of a hyperbolic tetrahedron. We comment on the relevance of our results to scrambling and the holographic reconstruction of the bulk physics near black hole horizons.

  15. Conformity of Goods in International Sales

    DEFF Research Database (Denmark)

    Henschel, Rene Franz

    The Conformity of Goods in International Sales gives a systematic analysis of Article 35 in the United Nations Convention on Contracts for the International Sale of Goods (CISG). Based on a detailed analysis of the most important cases and leading academic writing, Article 35 is described...... 9 CISG and the UNIDROIT Principles of International Commercial Contracts. The relation to domestic rules competing with Article 35, for instance the rules on validity and the rules on non-contractual liability, are analysed and so is the relation to selected domestic sales law, e.g. the United...... States Uniform Commercial Code (UCC), the new German and Chinese Civil Codes and the sales codes of the Scandinavian countries. The remedies available to the buyer are also analysed. The overall conclusion is that Article 35 is generally interpreted in an autonomous and dynamic way by the various courts...

  16. 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.)

  17. Physical inactivity is associated with low self efficacy and social support among patients with hypertension in Nigeria.

    Science.gov (United States)

    Idowu, O A; Adeniyi, A F; Atijosan, O J; Ogwumike, O O

    2013-06-01

    BACKGROUND Physical inactivity is a major factor in the development of many chronic illnesses, including hypertension. Evidence highlighting links among physical activity participation and psychosocial constructs such as self efficacy, social support and perceived barriers among hypertensive patients in the Nigerian population is scarce. This study explored the associations between physical activity and each of self efficacy, social support and perceived barriers. METHODS Two hundred and twelve patients receiving treatment in two tertiary health institutions located in Ekiti State, Nigeria were surveyed cross-sectionally. Physical activity level, self efficacy, social support and perceived barriers were measured with the International Physical Activity Questionnaire, Exercise Self-Efficacy Scale, Medical Outcomes Social Support Scale and Exercise Benefits and Barrier Scale respectively. RESULTS Level of physical activity was significantly associated with self efficacy (r(s) = 0.67, p physically inactive. However, no association was found between physical activity level and perceived barriers (r(s) = 0.07, p > 0.01, = 0.005). CONCLUSION Most of the hypertensive patients presented with low levels of physical activity. Physical activity was associated with psychosocial constructs including self efficacy and social support but not with perceived barriers.

  18. 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

  19. The Biological Bases of Conformity

    Science.gov (United States)

    Morgan, T. J. H.; Laland, K. N.

    2012-01-01

    Humans are characterized by an extreme dependence on culturally transmitted information and recent formal theory predicts that natural selection should favor adaptive learning strategies that facilitate effective copying and decision making. One strategy that has attracted particular attention is conformist transmission, defined as the disproportionately likely adoption of the most common variant. Conformity has historically been emphasized as significant in the social psychology literature, and recently there have also been reports of conformist behavior in non-human animals. However, mathematical analyses differ in how important and widespread they expect conformity to be, and relevant experimental work is scarce, and generates findings that are both mutually contradictory and inconsistent with the predictions of the models. We review the relevant literature considering the causation, function, history, and ontogeny of conformity, and describe a computer-based experiment on human subjects that we carried out in order to resolve ambiguities. We found that only when many demonstrators were available and subjects were uncertain was subject behavior conformist. A further analysis found that the underlying response to social information alone was generally conformist. Thus, our data are consistent with a conformist use of social information, but as subjects’ behavior is the result of both social and asocial influences, the resultant behavior may not be conformist. We end by relating these findings to an embryonic cognitive neuroscience literature that has recently begun to explore the neural bases of social learning. Here conformist transmission may be a particularly useful case study, not only because there are well-defined and tractable opportunities to characterize the biological underpinnings of this form of social learning, but also because early findings imply that humans may possess specific cognitive adaptations for effective social learning. PMID:22712006

  20. 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.

  1. 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

  2. Effect of Early- and Adult-Life Socioeconomic Circumstances on Physical Inactivity.

    Science.gov (United States)

    Cheval, Boris; Sieber, Stefan; Guessous, Idris; Orsholits, Dan; Courvoisier, Delphine S; Kliegel, Matthias; Stringhini, Silvia; Swinnen, Stephan P; Burton-Jeangros, Claudine; Cullati, Stéphane; Boisgontier, Matthieu P

    2018-03-01

    This study aimed to investigate the associations between early- and adult-life socioeconomic circumstances and physical inactivity (level and evolution) in aging using large-scale longitudinal data. This study used the Survey of Health Ageing and Retirement in Europe, a 10-yr population-based cohort study with repeated measurements in five waves, every 2 yr between 2004 and 2013. Self-reported physical inactivity (waves 1, 2, 4, and 5), household income (waves 1, 2, 4, and 5), educational attainment (wave of the first measurement occasion), and early-life socioeconomic circumstance (wave 3) were collected in 22,846 individuals 50 to 95 yr of age. Risk of physical inactivity was increased for women with the most disadvantaged early-life socioeconomic circumstances (odds ratio [OR], 1.49; 95% confidence interval [CI], 1.20-1.86). With aging, the risk of physical inactivity increased for both sexes and was strongest for those with the most disadvantaged early-life socioeconomic circumstances (OR, 1.04 (95% CI, 1.02-1.06) for women; OR, 1.02 (95% CI, 1.00-1.05) for men), with the former effect being more robust than the latter one. The association between early-life socioeconomic circumstances and physical inactivity was mediated by adult-life socioeconomic circumstances, with education being the strongest mediator. Early-life socioeconomic circumstances predicted high levels of physical inactivity at older ages, but this effect was mediated by socioeconomic indicators in adult life. This finding has implications for public health policies, which should continue to promote education to reduce physical inactivity in people at older ages and to ensure optimal healthy aging trajectories, especially among women with disadvantaged early-life socioeconomic circumstances.

  3. Structuring and sampling complex conformation space: Weighted ensemble dynamics simulations.

    Science.gov (United States)

    Gong, Linchen; Zhou, Xin

    2009-08-01

    Based on multiple simulation trajectories, which started from dispersively selected initial conformations, the weighted ensemble dynamics method is designed to robustly and systematically explore the hierarchical structure of complex conformational space through the spectral analysis of the variance-covariance matrix of trajectory-mapped vectors. The nondegenerate ground state of the matrix directly predicts the ergodicity of simulation data. The ground state could be adopted as statistical weights of trajectories to correctly reconstruct the equilibrium properties, even though each trajectory only explores part of the conformational space. Otherwise, the degree of degeneracy simply gives the number of metastable states of the system under the time scale of individual trajectory. Manipulation on the eigenvectors leads to the classification of trajectories into nontransition ones within the states and transition ones between them. The transition states may also be predicted without a priori knowledge of the system. We demonstrate the application of the general method both to the system with a one-dimensional glassy potential and with the one of alanine dipeptide in explicit solvent.

  4. The conformational dynamics of the mitochondrial Hsp70 chaperone.

    Science.gov (United States)

    Mapa, Koyeli; Sikor, Martin; Kudryavtsev, Volodymyr; Waegemann, Karin; Kalinin, Stanislav; Seidel, Claus A M; Neupert, Walter; Lamb, Don C; Mokranjac, Dejana

    2010-04-09

    Heat shock proteins 70 (Hsp70) represent a ubiquitous and conserved family of molecular chaperones involved in a plethora of cellular processes. The dynamics of their ATP hydrolysis-driven and cochaperone-regulated conformational cycle are poorly understood. We used fluorescence spectroscopy to analyze, in real time and at single-molecule resolution, the effects of nucleotides and cochaperones on the conformation of Ssc1, a mitochondrial member of the family. We report that the conformation of its ADP state is unexpectedly heterogeneous, in contrast to a uniform ATP state. Substrates are actively involved in determining the conformation of Ssc1. The J protein Mdj1 does not interact transiently with the chaperone, as generally believed, but rather is released slowly upon ATP hydrolysis. Analysis of the major bacterial Hsp70 revealed important differences between highly homologous members of the family, possibly explaining tuning of Hsp70 chaperones to meet specific functions in different organisms and cellular compartments. 2010 Elsevier Inc. All rights reserved.

  5. "Star" morphologies of charged nanodrops comprised of conformational isomers

    Science.gov (United States)

    In Oh, Myong; Paliy, Maxim; Consta, Styliani

    2018-01-01

    We study the spatial distribution of conformational isomers surrounding a central macroion in a charged droplet with linear dimensions in the nanometer range. Dimethyl carbonate and formic acid are selected as typical solvents that undergo isomerization and a charged buckyball (C60) is selected as a representative example of a macroion. The study is performed by atomistic molecular dynamics simulations. We find that when the charge of the buckyball is above a threshold value, it induces the formation of concentric shells of different conformational isomers surrounding the macroion. The presence of layers with different dielectric properties necessitates the use of different state equations for the solvent polarization in each layer. We find that at a high charge state of the buckyball, the nearest layer to the macroion comprises the conformers with the highest dipole moment. The interface of the outer layers of conformers is characterized by "ray"-forming structures of the higher dielectric constant isomers penetrating into the layer of the lowest dielectric constant isomers. For high values of the solvent dielectric constant, the charged droplet acquires a "star"-like global shape. We demonstrate that these distinct droplet structures are a manifestation of charge-induced instability. We describe this simulation-based phenomenology by an analytical theory that supports this conclusion. The findings suggest new experimental research venues that may explore the reactivity and assembly of molecules within regions of different dielectric properties in droplets.

  6. Shift in the Equilibrium between On and Off States of the Allosteric Switch in Ras-GppNHp Affected by Small Molecules and Bulk Solvent Composition

    Energy Technology Data Exchange (ETDEWEB)

    Holzapfel, Genevieve; Buhrman, Greg; Mattos, Carla (NCSU)

    2012-08-31

    Ras GTPase cycles between its active GTP-bound form promoted by GEFs and its inactive GDP-bound form promoted by GAPs to affect the control of various cellular functions. It is becoming increasingly apparent that subtle regulation of the GTP-bound active state may occur through promotion of substates mediated by an allosteric switch mechanism that induces a disorder to order transition in switch II upon ligand binding at an allosteric site. We show with high-resolution structures that calcium acetate and either dithioerythritol (DTE) or dithiothreitol (DTT) soaked into H-Ras-GppNHp crystals in the presence of a moderate amount of poly(ethylene glycol) (PEG) can selectively shift the equilibrium to the 'on' state, where the active site appears to be poised for catalysis (calcium acetate), or to what we call the 'ordered off' state, which is associated with an anticatalytic conformation (DTE or DTT). We also show that the equilibrium is reversible in our crystals and dependent on the nature of the small molecule present. Calcium acetate binding in the allosteric site stabilizes the conformation observed in the H-Ras-GppNHp/NOR1A complex, and PEG, DTE, and DTT stabilize the anticatalytic conformation observed in the complex between the Ras homologue Ran and Importin-{beta}. The small molecules are therefore selecting biologically relevant conformations in the crystal that are sampled by the disordered switch II in the uncomplexed GTP-bound form of H-Ras. In the presence of a large amount of PEG, the ordered off conformation predominates, whereas in solution, in the absence of PEG, switch regions appear to remain disordered in what we call the off state, unable to bind DTE.

  7. Conformational Transitions and Convergence of Absolute Binding Free Energy Calculations

    Science.gov (United States)

    Lapelosa, Mauro; Gallicchio, Emilio; Levy, Ronald M.

    2011-01-01

    The Binding Energy Distribution Analysis Method (BEDAM) is employed to compute the standard binding free energies of a series of ligands to a FK506 binding protein (FKBP12) with implicit solvation. Binding free energy estimates are in reasonably good agreement with experimental affinities. The conformations of the complexes identified by the simulations are in good agreement with crystallographic data, which was not used to restrain ligand orientations. The BEDAM method is based on λ -hopping Hamiltonian parallel Replica Exchange (HREM) molecular dynamics conformational sampling, the OPLS-AA/AGBNP2 effective potential, and multi-state free energy estimators (MBAR). Achieving converged and accurate results depends on all of these elements of the calculation. Convergence of the binding free energy is tied to the level of convergence of binding energy distributions at critical intermediate states where bound and unbound states are at equilibrium, and where the rate of binding/unbinding conformational transitions is maximal. This finding mirrors similar observations in the context of order/disorder transitions as for example in protein folding. Insights concerning the physical mechanism of ligand binding and unbinding are obtained. Convergence for the largest FK506 ligand is achieved only after imposing strict conformational restraints, which however require accurate prior structural knowledge of the structure of the complex. The analytical AGBNP2 model is found to underestimate the magnitude of the hydrophobic driving force towards binding in these systems characterized by loosely packed protein-ligand binding interfaces. Rescoring of the binding energies using a numerical surface area model corrects this deficiency. This study illustrates the complex interplay between energy models, exploration of conformational space, and free energy estimators needed to obtain robust estimates from binding free energy calculations. PMID:22368530

  8. Conformational study of glyoxal bis(amidinohydrazone) by ab initio methods

    Science.gov (United States)

    Mannfors, B.; Koskinen, J. T.; Pietilä, L.-O.

    1997-08-01

    We report the first ab initio molecular orbital study on the ground state of the endiamine tautomer of glyoxal bis(amidinohydrazone) (or glyoxal bis(guanylhydrazone), GBG) free base. The calculations were performed at the following levels of theory: Hartree-Fock, second-order Møller-Plesset perturbation theory and density functional theory (B-LYP and B3-LYP) as implemented in the Gaussian 94 software. The standard basis set 6-31G(d) was found to be sufficient. The default fine grid of Gaussian 94 was used in the density functional calculations. Molecular properties, such as optimized structures, total energies and the electrostatic potential derived (CHELPG) atomic charges, were studied as functions of C-C and N-N conformations. The lowest energy conformation was found to be all- trans, in agreement with the experimental solid-state structure. The second conformer with respect to rotation around the central C-C bond was found to be the cis conformer with an MP2//HF energy of 4.67 kcal mol -1. For rotation around the N-N bond the energy increased monotonically from the trans conformation to the cis conformation, the cis energy being very high, 22.01 kcal mol -1 (MP2//HF). The atomic charges were shown to be conformation dependent, and the bond charge increments and especially the conformational changes of the bond charge increments were found to be easily transferable between structurally related systems.

  9. Study of conformation and dynamic of surfactant molecules in graphite oxide via NMR

    Energy Technology Data Exchange (ETDEWEB)

    Ai, X.Q. [Jiangsu Second Normal University, College of Physics and Electronic Engineering, Nanjing (China); Ma, L.G. [Nanjing Xiaozhuang University, School of Electronic Engineering, Nanjing (China)

    2016-08-15

    The conformation and dynamic of surfactant in graphite oxide (GO) was investigated by solid-state {sup 13}C magic-angle-spinning NMR and {sup 1}H-{sup 13}C cross-polarization/magic-angle-spinning NMR spectra. The conformation ordering of the alkyl chains in the confined system shows strong dependence on its orientation. While the alkyl chains parallel to the GO layer in lateral monolayer arrangement are in gauche conformation in addition to a small amount of all-trans conformation, those with orientation radiating away from the GO in paraffin bilayer arrangement is in all-trans conformation in addition to some gauche conformation even though high-order diffraction peaks appears. NMR results suggest that the least mobile segment is located at the GO-surfactant interface corresponding to the N-methylene group. Further from it, the mobility of the alkyl chain increases. The terminal methyl and N-methyl carbon groups have the highest mobile. The chains in all-trans conformational state are characterized as more rigid than chains with gauche conformation; each segment of the confined alkyl chains with the lateral monolayer arrangement exhibits less mobility as compared to that with the paraffin bilayer arrangement. (orig.)

  10. Conformation of eight-membered benzoannulated lactams by combined NMR and DFT studies.

    Science.gov (United States)

    Witosińska, Agnieszka; Musielak, Bogdan; Serda, Paweł; Owińska, Maria; Rys, Barbara

    2012-11-02

    The title compounds were synthesized, and their structure and conformational behavior in solution (NMR and DFT), in the gas phase (DFT), and, for some of them, in the solid state (X-ray) were investigated. The variable-temperature NMR spectra were employed to determine the conformational equilibria and the activation energy of the conformational changes of the eight-membered ring. The coalescence effects are assigned to racemization of the chiral ground-state conformation with a ring inversion barrier in the range of 38-100 kJ mol(-1) depending on the relative setting of the two strong conformational constraints: benzoannulation and the amide function. The second conformational process, interconversion between two different conformers, in the molecules of benzo[c]azocin-3-one, benzo[d]azocin-2-one, and benzo[d]azocin-4-one was observed. The natures of the conformers observed in solution were elucidated by analysis of experimental and calculated NMR data. The present results are discussed in conjunction with previous experimental and theoretical data on (Z,Z)-cyclooctadienes and their benzo analogues.

  11. Marital Status, the Economic Benefits of Marriage, and Days of Inactivity due to Poor Health

    Directory of Open Access Journals (Sweden)

    Jim P. Stimpson

    2012-01-01

    Full Text Available Purpose. This study explored whether the economic benefits of marriage mediate the association between marriage and health and if that relationship is conditional on the level of shared economic resources. Methods. Pooled, cross-sectional data from NHANES 2001–2006 were analyzed using multivariate zero-inflated negative binomial regression for the number of days of inactivity due to poor physical or mental health. Results. Persons that were divorced/separated reported the highest average number of days of inactivity (mean = 2.5 within a 30 day period, and married persons reported the lowest number of days of inactivity (mean = 1.4. Multivariate results indicated that widowed persons did not report significantly more days of inactivity than married persons. Income to poverty ratio reduced the size and eliminated statistical significance of the difference between divorced/separated and never married marital statuses compared to married persons. The interaction effect for marital status and income to poverty ratio was statistically significant suggesting that the relationship between marital status and inactivity is conditional on shared income. Conclusion. Marriage confers health protective benefits in part through pooled income relative to other marital statuses.

  12. Activity, inactivity, and screen time in relation to weight and fatness over adolescence in girls.

    Science.gov (United States)

    Must, Aviva; Bandini, Linda G; Tybor, David J; Phillips, Sarah M; Naumova, Elena N; Dietz, William H

    2007-07-01

    The impact of activity and inactivity on relative weight and fatness change are best evaluated longitudinally. We examined the longitudinal relationship of physical activity, inactivity, and screen time with relative weight status and percentage body fat (%BF) and explored how it differed by parental overweight status. Non-obese pre-menarcheal girls (173), 8 to 12 years old, were followed until 4 years post-menarche. %BF, BMI z-score, and time spent sleeping, sitting, standing, walking, and in vigorous activity were assessed annually. We developed a physical activity index to reflect time and intensity of activity. Inactivity was defined as the sum of time spent sleeping, sitting, and standing. Screen time was defined as time spent viewing television, videotapes, or playing video games. Parental overweight was defined as at least one parent with BMI>25. In separate linear mixed effects models, activity, inactivity, and screen time were unrelated to BMI z-score longitudinally, with and without accounting for parental overweight. After controlling for parental overweight, activity was inversely related (phistory of overweight represent a target population of high priority for interventions around physical activity and inactivity.

  13. Conformable derivative approach to anomalous diffusion

    Science.gov (United States)

    Zhou, H. W.; Yang, S.; Zhang, S. Q.

    2018-02-01

    By using a new derivative with fractional order, referred to conformable derivative, an alternative representation of the diffusion equation is proposed to improve the modeling of anomalous diffusion. The analytical solutions of the conformable derivative model in terms of Gauss kernel and Error function are presented. The power law of the mean square displacement for the conformable diffusion model is studied invoking the time-dependent Gauss kernel. The parameters related to the conformable derivative model are determined by Levenberg-Marquardt method on the basis of the experimental data of chloride ions transportation in reinforced concrete. The data fitting results showed that the conformable derivative model agrees better with the experimental data than the normal diffusion equation. Furthermore, the potential application of the proposed conformable derivative model of water flow in low-permeability media is discussed.

  14. Mitochondria isolated from local market potato tubers contain L-lactate dehydrogenase in an inactive state.

    Science.gov (United States)

    Paventi, Gianluca; Pizzuto, Roberto; Chieppa, Gabriella; Passarella, Salvatore

    2007-12-01

    In order to gain some insight into metabolism of mitochondria isolated from materials subjected to storage treatments, we compared mitochondria isolated from potato tubers grown and stored in the post-harvest without any chemicals (N-PTM), and tubers, from local market, treated for commercial purpose (T-PTM) with respect to the L-lactate metabolism. Although no oxygen consumption due to L-lactate was found in T-PTM, L-lactate dehydrogenase existence was shown as immunologically investigated. Consistently, no L-lactate dehydrogenase activity was detected. Contrarily, N-PTM proved to metabolize externally added L-lactate, with oxygen consumption and intramitochondrial pyridine nucleotide reduction. All together these findings show that commercial treatments of foodstuffs could result in changes in their metabolism.

  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. Lattice models and conformal field theories

    International Nuclear Information System (INIS)

    Saleur, H.

    1988-01-01

    Theoretical studies concerning the connection between critical physical systems and the conformal theories are reviewed. The conformal theory associated to a critical (integrable) lattice model is derived. The obtention of the central charge, critical exponents and torus partition function, using renormalization group arguments, is shown. The quantum group structure, in the integrable lattice models, and the theory of Visaro algebra representations are discussed. The relations between off-critical integrable models and conformal theories, in finite geometries, are studied

  17. Testing the role of action and inaction anticipated regret on intentions and behaviour.

    Science.gov (United States)

    Sandberg, Tracy; Hutter, Russell; Richetin, Juliette; Conner, Mark

    2016-09-01

    Anticipated regret (AR) has been suggested as a useful addition to the theory of planned behaviour (TPB) that captures affective influences. However, previous research has generally (1) assessed the impact of AR in relation to one behaviour (action or inaction) when considering TPB variables in relation to the alternative behaviour, (2) not controlled for affective attitudes or past behaviour, and (3) examined only one or two behaviours. In two studies across several behaviours, the present research showed that even when controlling for affective attitudes, past behaviour, and other TPB variables towards action, action and inaction AR each added to the prediction of intentions across multiple behaviours. The two studies also showed that inaction regret was generally the stronger predictor, although action regret was important for some types of behaviour. Implications and issues for further research are discussed. © 2016 The British Psychological Society.

  18. Novel conformation of an RNA structural switch.

    Science.gov (United States)

    Kennedy, Scott D; Kierzek, Ryszard; Turner, Douglas H

    2012-11-20

    The RNA duplex, (5'GACGAGUGUCA)(2), has two conformations in equilibrium. The nuclear magnetic resonance solution structure reveals that the major conformation of the loop, 5'GAGU/3'UGAG, is novel and contains two unusual Watson-Crick/Hoogsteen GG pairs with G residues in the syn conformation, two A residues stacked on each other in the center of the helix with inverted sugars, and two bulged-out U residues. The structure provides a benchmark for testing approaches for predicting local RNA structure and a sequence that allows the design of a unique arrangement of functional groups and/or a conformational switch into nucleic acids.

  19. Conformal Dimensions via Large Charge Expansion.

    Science.gov (United States)

    Banerjee, Debasish; Chandrasekharan, Shailesh; Orlando, Domenico

    2018-02-09

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

  20. A Framework for Online Conformance Checking

    DEFF Research Database (Denmark)

    Burattin, Andrea; Carmona, Josep

    2017-01-01

    Conformance checking – a branch of process mining – focuses on establishing to what extent actual executions of a process are in line with the expected behavior of a reference model. Current conformancechecking techniques only allow for a-posteriori analysis: the amount of (non-)conformant behavior...... is quantified after the completion of the process instance. In this paper we propose a framework for online conformance checking: not only do we quantify (non-)conformant behavior as the execution is running, we also restrict the computation to constant time complexity per event analyzed, thus enabling...